1. health and fitness
2. disease

4/11/2015
The First 6 Hours of Sepsis
Diagnosis and Management-2015-Part I
Emanuel P. Rivers, MD, MPH
Vice Chairman and Research Director
Emergency and Surgical Critical Care Medicine
Henry Ford Hospital
Clinical Professor, Wayne State University
Detroit, Michigan
Institute of Medicine, National Academies
1
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The First 6 Hours of Sepsis Diagnosis and
Management-2015-Part I
8:00 AM - 8:30 AM
(4/11)
Starting a Sepsis Program: Practice, Politics and
Performance
10:30 AM - 11:20 AM
(4/11)
The First 6 Hours of Sepsis Diagnosis and
Management-2015-Part II
1:30 PM - 2:00 PM
(4/11)
Resuscitating Sepsis: After ProCESS, ARISE and
ProMISE
4:25 PM - 5:15 PM
(4/11)
Steroid Use in Critical Illness - Update 2015
8:00 AM - 8:30 AM
(4/12)
What is Sepsis?:
The Early Pathogenesis
Sepsis: A Complex and Dynamic Landscape
Systemic Inflammation
or Inflammatory
Organism
Source
Sepsis
Response
Systemic Inflammatory
Response Syndrome (SIRS)
A clinical response arising from a nonspecific insult,
including 2 of the following:
Diffuse endothelial
•
•
•
•
oC
disruption and
Temperature ≥38oC or ≤36
microcirculation defects
OR
General
Intensive
At
Emergency
OutHome
Patient
Practice
Care
or
HR ≥90 beats/min
and
Recovery
Global Tissue
Department
Residence
Setting
Floors
Unit
Respirations
≥20/min
Hypoxia and
Organ
WBC
count ≥12,000/mm3 Severe
or Sepsis
Dysfunction
≤4,000/mm3 or >10% bands
• PaCO2 < 32mmHg
Septic Shock
Multiple Organ
Dysfunction and
Refractory Hypotension
2
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5-10%
10-20%
20-30%
30-50%
Chronic Lung
Disease (ARDS)
Disabilities
(Amputations)
Neuromuscular
Disorders
Chronic Heart
Failure
Morbidity or
Disabilities
Psychiatric
Disease
Kidney Failure
and Dialysis
Cases per year Mortality (%)
Sepsis
859,858
15-20
Severe Sepsis
791,000
27-40
Septic Shock
200,000
36-47
Pneumonia
1,187,180
5-9
Stroke
591,996
6-7
Acute Myocardial Infarction
540,891
10
Trauma
697,025
5-16
3
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A Need to Change the
Paradigm of
Current Sepsis Management
Time Sensitive Diseases
Changing the Paradigm of Practice
AMI
Stroke
< 10%
7%
Trauma
< 5%
4
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What About
Guidelines for Sepsis?
5
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2004, 2008, 2012
6
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The Evolution of Early Sepsis Care
NEJM, 2014
NEJM, 2014
What’s is Early Sepsis Care in 2015?
The Fundamental Evidence
for the Bundle Components
The Origin of SIRS
7
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Roger Bone
JAMA, 1992
SIRS in the Emergency Department
Ander, AEM, 1996
The Timing of Antibiotics
8
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1.
Natanson C, Danner RL, Reilly JM, et al. Antibiotics versus
cardiovascular support in a canine model of human septic shock. Am J
Physiol 1990;259:H1440-7.
Dogs with septic shock induced by an
intraperitoneal clot containing E. coli.
No
Therapy
Antibiotics
(cefoxitin
and
gentamicin)
0%
13%
Survival
CV support
(fluids &
dopamine
to
hemodynamic
end points.
CV support
and
antibiotics
43%
13%
Crit Care Med,
2014
9
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Crit Care Med,
2014
8.5% Increase in Mortality
Importance of Blood Cultures and
Adequacy of Antibiotics
5,715 patients,
Retrospective,
Multicenter
10
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10.3%
52%
9.45
11
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The Importance of
Source Control
Crit Care Med, 2004
12
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Every hour of delay from admission to surgery was associated with an adjusted
2.4% decreased probability of survival compared with the previous hour.
Patients who had surgical source control delayed for
more than 6 hours had a significantly higher 28-day
mortality (42.9% vs. 26.7%, P <0.001)
This delay was independently associated with an
increased risk of death
13
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14
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Risk Stratification for
Early Detection of High
Risk Patients:
Changing the way we
detect
illness severity
Systolic
Blood Pressure
Diastolic
Blood Pressure
Stephen Hales - 1733
A Subtle and Deadly Disease Transition
Using a 279 year old definition
ER or Ward
ICU
MAP ~ SVR X CO
15
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Global Tissue Hypoxia:
A More Sensitive Measure of Shock
OXYGEN
DEMAND
OXYGEN
DELIVERY
Global Tissue
Hypoxia
OXYGEN
BALANCE
Lactic Acid
> 4 mM/L
Seminal Lactate Studies
Where did a Lactate cut point of 4 come from?
Broder G, Weil MH.
Science 1964;143:1457-1459
56 patients with clinical signs of shock:
Hypovolemia (17), Sepsis (9), cardiac failure (7),
neural dys. & endocrine def. (4), vascular obs. (2),
mixed (9), unclassified (8)
Screening for Severe Illness in the ED
Infection and Lactate (LA > 4 mM/L)
#SIRS
 2 of the following is SIRS:
– Temperature ≥38oC or ≤36oC
– HR ≥ 90 beats/min
– Respirations ≥ 20/min
– WBC count ≥12,000/mm3
or ≤4,000/mm3
or >10% bands
– PaCO2 < 32mmHg
0
1
2
3
4
SIRS SIRS + LA SIRS + LA
Ward (%) Ward (%)
ICU
11.6
14.7
34.6
55.4
70.0
33.3
15.4
40.0
84.6
100
0
0
62.5
94.5
100
Aduen, JAMA, 1994; Grzybowski, Chest, 1999
16
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Crit Care Med, 2014
Outcome Impact of
Lactate Measurements
51.4 to 29% (11.4%) - No Hypotension
58.6 to 44.5% (12.1%) - Hypotension
What patients are at high risk for
global tissue hypoxia?
SvO2
4 mM/L
•
•
•
•
•
•
Case
78 year old female
2 weeks after AAA
T – 39o C
Cough
Brown sputum
Right sided chest
pain
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The importance of
early detection of high risk
patients
18
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12.1% of All
Cardiac Arrests
Are pnuemonia
Importance of the Fluid Challenge
19
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2.5 – 3.5 Liters for 70 kg
20 - 40cc per kg fluid challenge
20
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Is Fluid Administration Within Six Hours Early Enough for
Better Patient Outcomes in Sepsis Septic Shock
• Results:
– 594 patients, median age was 70 (58-80) years.
– Adjusted for chronic co-morbidity, acute illness, age and fluid given in
the first 6 hours.
• In fluids within the first 3 hours:
– Survival at discharge 2085 ml (940-4080)
– Death at discharge 1600 ml (600-3010), p=0.007.
– In the latter 3 hours, median was 660 ml (290-1485) vs. 800 ml (3601680), p=0.09.
• Earlier fluid resuscitation (within the first 3 hours) reduces
mortality. [odds ratio 0.34 (95% CI, 0.15 to 0.75), p=0.008].
Lee, Sarah; Li, Guangxi; Jaffer-Sathick, Insara; Valerio-Rojas, Juan Carlos;
Cartin-Ceba, Rodrigo; Kashyap, Rahul, Crit Care Med, 2012
Repeat Lactate:
The Implications of
Lactate Clearance
21
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Initial Lactate minus Later Lactate
Initial Lactate
Bad
Good
Quartiles of Lactate Clearance
22
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Lactate Clearance
• Excellent Predictor when elevated
–MSOF
–Mortality
• Resuscitation endpoint
–Alactemia is common
–Relative changes
–An adjunct with other parameters
23
Care of the Hospitalized
Patient with Advanced Liver
Disease
William T. Browne, MD
Disclosures
• I have no conflict of interest to disclose
Objectives
• By the end of this session participants
will:
– Recognize the HIGH risk of mortality in
these patients
– Remember at least 3 tips for managing the
common complications of cirrhosis
encountered by hospitalists
– Consider early referral for transplant
evaluation in patients with decompensated
cirrhosis
Clinical Case
• 56 yr old male with a history of Hepatitis C
presents with confusion and dyspnea and is
admitted to the Hospital Medicine Service.
Family reports he’s “just not himself” but
has left by the time he arrives on the floor.
• Medications: lactulose, omeprazole,
furosemide, spironolactone, simvastatin
Physical Exam
•
•
•
•
•
•
•
•
•
•
Vitals: T 99.6, BP 87/45, HR 98, RR 20, O2 sats 91% on RA
Jaundiced, confused, somnolent but responds to loud or noxious stimuli
OP with poor dentition, dry mucous membranes; scleral icterus
No adenopathy
Cor RRR, Nl S1, S2, 2/6 SEM without radiation
Lungs clear anteriorly, dullness to percussion half way up on right
No obvious trauma, Moves all extremities but has asterixis
Abdomen distended with bulging flanks, fluid wave present, no rebound
or guarding, caput medusae
Extremities with 3+ pitting edema bilaterally, palmar erythema
Skin with some petechia where BP cuff compresses arm and spider
angiomata on chest
Labs / Images
•
•
•
•
•
•
BMP remarkable for Na 126, HCO3 18 with anion gap of 6, Cr 2.2 (0.9)
CBC remarkable for Hgb 9 (11.8), WBC 12, Plts 64k
ALT/AST normal, Alk Phos nl, T. Bili 9
INR 2.4
NH3 64
UA- SG 1.031, LE/nitrite/protein -, 1 WBC, 1 RBC
•
CXR- Right pleural effusion, no other acute cardiopulmonary pathology
•
Abdominal U/S- large ascites with thickened and distended gallbladder,
shrunken nodular liver c/w cirrhosis, reversal of flow in portal vein with
collateralization.
Assessment/Plan
Pathophysiology of Cirrhosis
Adapted from Hepatitis C Education Society: http://hepcbc.ca/stages-of-liver-disease/
Increased
Splanchnic
Vasodilation
Complications
__of Portal HTN___
Variceal Bleeding
Jaundice
Hepatic Encephalopathy
Ascites / SBP / HH
Increased
Hepatic
Resistance
Hepatorenal Syndrome
Hepatopulmonary Syndrome
Portal Vein Thrombosis
Portopulmonary HTN
Hepatocellular Carcinoma
The splanchnic circulation. (Redrawn with permission from Gelman S, Mushlin PS: Catecholamine induced changes
in the splanchnic circulation affecting systemic hemodynamics. Anesthesiology 100:434–439, 2004.)
Natural History and Prognosis
Portal HTN
Clinically
Significant
Portal HTN
HVPG >5
mm Hg
Compensated
Cirrhosis
7% new
varices/yr
HVPG >10
mm Hg
12% variceal
bleed/yr
HVPG >12
mm Hg
Decompensated
Cirrhosis
75% progress
within 10 years
Median Survival
2 years
Compensated
Baveno IV International Consensus Workshop Staging
System for Cirrhosis: 1-Year Outcome Probabilities
1
NO VARICES
NO ASCITES
2
VARICES
NO ASCITES
7%
1%
4.4%
3.4%
Decompensated
6.6%
4%
ASCITES 
VARICES
3
DEATH
20%
7.6%
BLEEDING 
ASCITES
4
57%
D’Amico G et al. J Hepatol. 2006;44:217-231.
Classification of Cirrhosis Severity
Determinants for Child-Turcotte-Pugh (CTP)
Points
1
2
3
Encephalopathy
None
Grade 1 - 2
(or precipitant-induced)
Grade 3 - 4
(or chronic)
Ascites
None
Mild/Moderate
(diuretic-responsive)
Severe
(diuretic-refractory)
<2
2-3
>3
>3.5
2.8 - 3.5
<2.8
<4
4-6
>6
Bilirubin (mg/dL)
Albumin (g/dL)
Prothrombin Time
(seconds prolonged)
Total Numerical
Score
Child-Pugh
Class
5-6
A
7-9
B
10 - 15
C
Patients in Class A are considered
“compensated”
Patients in Classes B and C are
considered “decompensated”
Adapted from Garcia-Tsao G et al. Am J Gastroenterol. 2009;104:1802-1829.
Classification of Cirrhosis Severity
Model for End Stage Liver Disease score
• MELD - determines the severity of liver disease based on:
– serum bilirubin,
– serum creatinine
– international normalized ration (INR)
• developed in 2002 by UNOS
• Calculation:
– [0.957 x (Serum creatinine mg/dL) + 0.378 loge (Total
bilirubin mg/dL) + 1.12 loge (INR) + 0.64] x 10
• Range: 6 – 40
– equates to estimated 3-month survival rates from 90% to
7%respectively
Most Common Causes of Death
Hepatorenal Syndrome
• Renal failure increases mortality 7X
• 50% mortality within one month
Sepsis
• Infections common- SBP, UTI, CAP, Skin
• 30% mortality at 1 month, 60% at 1 year
Variceal Hemorrhage
• 12% incidence of bleed per year, then
• 57% mortality at one year
Hepatocellular Carcinoma
• 4-30% incidence over 5 years depending on etiology of cirrhosis
and origin of patient
Lefton HB et al. Med Clin N Am. 2009;93:787-799.
D’Amico G et al. J Hepatol. 2006;44:217-231.
Assessment: Decompensated
cirrhosis with MELD 32 complicated by
1) Overt hepatic encephalopathy
6) Coagulopathy
2) Ascites
7) Hyponatremia
3) Right pleural effusion
8) Hypotension
4) Acute kidney injury
9) Hypoxia
5) Anemia
6) Distended gallbladder
6) Coagulopathy
Overt Hepatic Encephalopathy
(OHE)
• Associated with a poor prognosis
• Retrospective review of 111 cirrhotic patients for
12±17 months following first episode of acute OHE:
– 82 (74%) died during follow-up period
– Survival probability
• 42% at 1 year
• 23% at 3 years
Bustamante J et al. J Hepatol. 1999;30(5):890-895.
Treatment Goals for OHE
• Provision for supportive care
• Identification and removal of precipitating factors
– Infection, GI bleed, dehydration
• Reduction of nitrogenous load from gut
• Correction of electrolyte abnormalities
• Long-term therapy assessment
– Control of potential precipitating factors
– Higher likelihood of recurrent encephalopathy
– Assessment of need for liver transplantation
Adapted from Blei AT et al. Am J Gastroenterol. 2001;96(7):1968-1976.
Lactulose
• Currently the mainstay of therapy of HE; ~70% to 80% of
patients with acute and chronic HE improve with lactulose
treatment
• Mechanism of action:
– A non-absorbable dissacharide that is fermented in the
colon
– Metabolism by the bacterial flora in the colon to lactic acid
lowers the colonic pH
– Cathartic effect can increase fecal nitrogen excretion with
up to a 4-fold increase in stool volume
Mullen KD et al. Semin Liver Dis. 2007;27(Suppl 2):32-47.
Ferenci P. Semin Liver Dis. 2007;27(suppl 2):10-17.
Bajaj JS. Aliment Pharmacol Ther 2010;31:537-547.
Rifaximin
• Minimally absorbed (<0.4%) oral antibiotic
• Broad-spectrum in vitro activity against aerobic and
anaerobic enteric bacteria
• No clinical drug interactions reported
• No dosing adjustment required in patients with liver
disease or renal insufficiency
• Approved for overt recurrent HE risk reduction in
patients ≥18 years of age
Bass NM. Semin Liver Dis. 2007;27(suppl 2):18-25.
Mullen KD et al. Semin Liver Dis. 2007;27(suppl 2):32-47.
Proportion of Patients Without
Breakthrough HE (%)
Rifaximin Trial: Time to First Breakthrough HE Episode
Primary End Point
Rifaximin*
(77.9%)
Placebo*
(54.1%)
*Rifaximin 550 mg or placebo twice daily
Hazard ratio with rifaximin, 0.42 (95% Cl, 0.28–0.64)
P<0.001
Days Since Randomization
Bass NM et al. N Engl J Med. 2010;362:1071-1081.
Key Points
• Always look for and correct inciting factors:
infection, bleeding, dehydration,
constipation, portal vein clot, porto-systemic
shunt, medications
• 1st Line Rx: Lactulose 45-90 gm/d (NNT 4)
– Nurse driven protocol (oral, NG, or PR)
• If on lactulose, add Rifaximin 550 mg bid
• DO NOT check Ammonia levels daily
Ascites
• Most common complication of cirrhosis
• ~60% of patients with compensated cirrhosis develop ascites
within 10 years
• 50% mortality rate within 3 years
• Hepatic hydrothorax may be seen with minimal abdominal ascites
• SBP a risk in patients with high SAAG (serum albumin – ascites
albumin = > 1.1) PPIs increase risk > 4X
• Patients should generally be considered for liver transplantation
referral
Arroyo V, Colmenero J. J Hepatol. 2003;38:S69-S89.
European Association for the Study of the Liver. J Hepatol. 2010;53:397-417.
Illustration from: http://www.hepatitis.va.gov/vahep?page=cirrh-06-02. Accessed 02/15/11. (illustration??)
Management of Ascites
First-Line Therapy
Second-Line Therapy
Tense ascites
Paracentesis
Sodium restriction
(<2 Gm/24 Hrs)
and diuretics*
Refractory
Ascites 10 %
• Repeated large volume
paracentesis (LVP)
• TIPS
• Liver Transplantation
Non-tense ascites
*Diuretics: Spironolactone 100 mg/day,
furosemide 40 mg/day or bumetanide
1 mg/day; uptitrate stepwise to
spironolactone 400 mg/day, furosemide
160 mg/day or bumetanide 4 mg/day as
tolerated
Albumin
infusion of 8-12 gm/liter of fluid
removed is a consideration for repeated
LVP; post-paracentesis albumin infusion
may not be necessary for < 5 liters removed
Adapted from Runyon BA. Hepatology. 2009; 49:2087-2107.
Systematic Review of
Safety of Paracentesis
Nine cases of severe bleeding were identified among
4729 procedures. The occurrence of severe hemorrhage
represented 0.19% of all procedures with a death rate of
0.016%. Bleeding was not related to operator
experience, elevated international normalized ratio or
low platelets. It occurred in patients with high model for
end-stage liver disease and Child-Pugh scores.
Furthermore, some degree of renal failure was present
in all but one patient.
Pache, I., and M. Bilodeau. "Severe haemorrhage following abdominal paracentesis for ascites in patients with liver
disease." Alimentary pharmacology & therapeutics 21.5 (2005): 525-529.
Needle Entry Points
AASLD Practice Guidelines:
Ascitic Fluid Analysis
Routine
Optional
Unusual
Cell count and
differential
Culture in blood
culture bottles
Acid-fast bacteria
smear and culture
Albumin
Glucose
Cytology
Total protein
Lactose
dehydrogenase
Trigylceride
Amylase
Bilirubin
Gram’s stain
Runyon BA. Hepatology. 2009; 49:2087-2107.
Spontaneous Bacterial Peritonitis: Diagnosis
• Diagnosis of SBP:
– Positive ascitic fluid bacterial culture
– Elevated ascitic fluid absolute PMN count (ie, 250
cells/mm3 [0.25 x 109/L])
– No evident intra-abdominal source of infection
Runyon BA. Hepatology. 2009; 49:2087-2107.
Prevention of SBP –
Prophylaxis
Drug Therapy
Dose /Duration
Norfloxacin
400 mg/day orally
Ceftriaxone
1g/day IV for 7 days Double‐strength trimethoprim/sulfamethoxazole
5 doses/week
Ciprofloxacin
750 mg as single oral dose/week
Intermittent dosing of prophylactic antibiotics may select resistant
flora; daily dosing preferred
Key Points
• Always perform a diagnostic paracentesis
• Always give 8 gm/l albumin when taking over 5
liters of ascites
• Always give 1.5 gm/kg albumin on Day 1 and
1.0 gm/kg albumin on Day 3 for SBP
• Always start SBP prophylaxis after first episode
• Avoid chest tubes in a hepatic hydrothorax
• Avoid PPI’s in patients with ascites without PUD
Renal Injury in Cirrhosis
Hospitalized patients with cirrhosis
Chronic renal failure
1%
Pre-renal
68%
Intra-renal (ATN, GMN)
32%
AKI
19%
Post-renal (obstructive)
<1%
Not volume-responsive
Volume-responsive
66%
 Infection
 Hypovolemia
 Vasodilators
 Other
HRS type 1
25%
Garcia-Tsao G et al. Hepatology. 2008;48:2064-2077.
HRS type 2
9%
Survival Is Decreased With Renal Dysfunction
Survival Among Patients
With Cirrhosis and
Hepatorenal Syndrome
Survival in Cirrhosis
Based on Level
of Renal Dysfunction
1.0
1.0
0.8
0.8
0.6
0.4
Creatinine 1.2-1.5mg/dL
0.2
Creatinine >1.5mg/dL
0.0
0
0.6
Creatinine <1.2 mg/dL
Survival
Survival
P<0.001
1
2
3
Years
4
5
0.4
Refractory ascites
0.2
0.0
0
Type 1 hepatorenal syndrome
1
2
3
4
5
6
Months
Blackwell: Science, Oxford, UK.
Gines et al. N Engl J Med. 2004;350:1646-1654.
Prevention of Acute Renal Injury in Cirrhotics
• Prevent/treat volume depletion or vasodilatation
– Careful use of diuretics
– Avoidance of diarrhea with use of lactulose
– Use of albumin after large-volume paracentesis
• Avoid use of aminoglycosides and NSAIDs
• Aggressively treat hypovolemia/hypotension
occurrence
Garcia-Tsao G et al. Hepatology. 2008;48:2064-2077.
Volume Challenge
• 1 gm/kg body weight up to 100 gm
albumin infusion for at least 2 days
• Withdrawal of antibiotics
• Failure of improvement in renal function
is concerning for hepatorenal syndrome
(part of diagnostic criteria)
Hepatorenal Syndrome: Risk Factors
• Development of bacterial infections, particularly
SBP, is the most important risk factor
– Hepatorenal syndrome develops in ~30% of patients
with spontaneous bacterial peritonitis
– Treatment with albumin infusion/antibiotics reduces
the risk of developing hepatorenal syndrome and
improves survival
European Association for the Study of the Liver. J Hepatol. 2010;53:397-417.
Hepatorenal Syndrome: Prognosis
• The prognosis of hepatorenal syndrome is poor
– Average median survival ~ 3 months
– High MELD score and type 1 hepatorenal syndrome
are associated with very poor prognosis
• Median survival of patients with untreated type 1
hepatorenal syndrome is ~ 1 month
European Association for the Study of the Liver. J Hepatol. 2010;53:397-417.
Key Points
• Always closely monitor renal function in
hospitalized cirrhotic patients
• Always correct volume depletion in the
setting of a rising creatinine
Gastroesophageal Varices
• Gastroesophageal varices present in ~50% of
patients with cirrhosis
– Presence correlates with severity of liver disease
– 40% of Child A patients have varices
– 85% of Child C patients have varices
• Cirrhotic patients without varices develop them
at a rate of 7-8% per year
– Patients with small varices develop large varices at a
rate of 8% per year
Garcia-Tsao G et al. Hepatology. 2007;46:922-938.
Gastroesophageal Variceal Hemorrhage
• Occurs at a yearly rate of 5% to 15%
• Most important predictor of hemorrhage is size of
varices
• Other predictors of hemorrhage are:
– Decompensated cirrhosis (Child B/C)
– Endoscopic presence of red wale marks
• Associated with a mortality of ≥20% at 6 weeks
• Bleeding ceases spontaneously in ≤40% of patients
Garcia-Tsao G et al. Hepatology. 2007;46:922-938.
Cirrhosis Screening and Surveillance Management
Esophagogastroduodenoscopy
No
varices
Repeat endoscopy in
3 years (well
compensated);
in 1 year if
decompensated
Small varices (<5 mm),
Child B/C, red wales
Beta-blocker
prophylaxis
No beta-blocker
prophylaxis
Adapted from Garcia-Tsao G et al. Hepatology. 2007;46:922-938.
Medium or
large varices
Child Class A, no red
wales: Beta blockers
Child class B/C, red
wales: Beta blockers,
or endoscopic band
ligation
Management of Acute Hemorrhage
• Patients with suspected acute variceal hemorrhage
require intensive-care unit setting for resuscitation and
management
• Acute GI hemorrhage requires:
– Intravascular volume support
– Blood transfusions
– Maintaining hemoglobin of ~7-9 g/dL
• Institute short-term (5-7day) antibiotic prophylaxis
• Initiate therapy with somatostatin (or its analogs)
• Perform esophagogastroduodenoscopy within 12
hours; treat with endoscopic band ligation or
sclerotherapy
Garcia-Tsao G et al. Hepatology. 2007;46:922-938.
Acute Hemorrhage: Role of Early TIPS
García-Pagán, Juan Carlos, et al. "Early use of TIPS in patients with cirrhosis and variceal bleeding." New England Journal of
Medicine 362.25 (2010): 2370-2379.
Bacterial Infection and Variceal Bleeding
• Variceal bleeding associated with increased risk of
bacterial infection
– SBP (spontaneous bacterial peritonitis), urinary tract infection,
pneumonia or bacteremia
• Develops in 20% of patients within 48 hours and in
35% to 66% of patients within 2 weeks
• Compared to patients without infection, presence of
infection is associated with
– Failure to control bleeding (65% vs 15%)
– Early rebleeding
– Mortality (40% vs 3%)
Vivas S et al., Dig Dis Sci. 2001;46:2752-2757.
Antibiotic Prophylaxis During/After
Acute Variceal Bleeding
• Prophylatic ofloxacin vs
antibiotics only at
diagnosis of infection
• Less rebleeding within
7 days
•  blood transfusions
for rebleeding
Rebleeding
•  infections (2/59 vs 16/61)
1.0
Prophylactic antibiotics (n=59)
0.8
On-demand antibiotics (n=61)
0.6
0.4
0.2
• Prophylactic antibiotics
recommended in
management of acute
variceal hemorrhage
0.0
0
1
2
3 12 18 24 30
Follow-up (Months)
Hou M-C et al. Hepatology. 2004;39:746-753.
Key Points
• Always consider variceal bleeding in the
differential for anemia in a cirrhotic
• Always give prophylactic antibiotics in
setting of a variceal bleed- they save lives
• Always manage in the ICU and get an EGD
for therapy and risk stratification
• Always consider beta blocker prophylaxis
on discharge to prevent or delay rebleed
Liver Transplantation Options
Cirrhosis Was the Most Common
Reason for Liver Transplant in 2007
Non-cholestatic
cirrhosis
Cholestatic liver
disease/cirrhosis
Acute hepatic necrosis
Biliary atresia
Metabolic diseases
Malignant neoplasms
Other/unknown
N = 6223 Recipients of Deceased Donor Livers
Available at: http://optn.transplant.hrsa.gov/ar2008/904a_rec-dgn_li.htm. Accessed 10/05/10.
Contraindications - Absolute
• Extrahepatic malignancy unless tumor free for >2
years and probability of recurrence <10%
• Alcoholic hepatitis /untreated alcoholism /
chemical dependency
• Extrahepatic sepsis unresponsive to medical
therapy
• High dose or multiple pressors
• Severe multiorgan failure
• Severe psychological disease likely to affect
compliance
• Extensive portal vein and mesenteric vein
thrombosis
• Pulmonary HTN (mean PAP >35mmHg)
Contraindications - Relative
•
•
•
•
General debility
Portal vein thrombosis
HIV infection
Extensive prior abdominal
surgery
• social isolation
Listing for Transplant
• Once evaluation is completed and
contraindications excluded must meet
minimum listing criteria: CPT=7
• Currently a MELD score of 15
• UNOS: organs allocated locally then
nationally
• Organs are matched by blood type and size
• Priority is based on MELD score
Wait List and Transplant Activity for Liver
1999–2008
26,407
Number
of
Patients
20,965
 On Waiting List Annually
 Received Transplants Annually
 Died While on Waiting List Annually
6,069
4,49
8
1,894
1,554
Year
US department of Health and Human Services OPTN. Available at: http://optn.transplant.hrsa.gov/data/.
Accessed 02/12/11.
Patients Awaiting Transplantation
Management
•
•
•
•
Close follow-up with primary GI MD
Preparation/support of family and patient
Treat promptly complications
Avoid therapies/interventions that would make
transplantation more difficult
-Nephrotoxins
-RUQ surgery/shunts
-Anesthesia
• Consider living donor transplant
cumulative percent
Patient survival by era
100
90
80
70
60
50
40
30
20
10
0
1968-1970
1971-1975
1976-1980
1981-1985
1986-1990
1991-1995
1996-
0
1
2
3
4
5
years posttransplant
• Patients on waiting list have highest risk
of death in USA with poor availability of
organs
• Where does your state stand?
LDLT survival 83% at 5 years
INTENTION TO TREAT ANALYSIS:
Risk of Death is 40% lower compared
to
•No living donor
•On the wait list for DDLT
•HCC patients MELD>15 risk of death
is 29% lower with LDLT
•NO benefit of LDLT in HCC MELD<15
(due to allocation points)
Assessment: Decompensated
cirrhosis with MELD 32 complicated by
1) Overt hepatic encephalopathy
 Treat infection, bleed, correct
hyponatremia, give lactulose, rifaximin
6) Anemia variceal bleed

2) Ascites
 Tap regardless of INR/plts, treat
SBP, give albumin d1 and d3 and
for LVP, home on SBP
prophylaxis but NO PPI
3) Right pleural effusion Hepatic Hydrothorax. No chest
tube.
4) Acute kidney injury
 Likely pre-renal. Hold diuretics.
Volume challenge with 100 gm
albumin X 2 days
ICU, EGD, octreotide, ?early TIPS,
prophylactic abx NOW, beta
blocker on d/c.
7) Coagulopathy

Can’t assume auto-anticoagulated,
low risk of bleed with paracentesis
8) Hyponatremia

SIADH and diuretics- hold
diuretics, volume repletion
9) Distended gallbladder

VERY HIGH SURGICAL RISK.
Percutaneous gallbladder drainage
if acute choly is confirmed.
Suspect simply related to ascites.
Objectives
• By the end of this session participants
will:
– Recognize the HIGH risk of mortality in
these patients
– Remember at least 3 tips for managing the
common complications of cirrhosis
encountered by hospitalists
– Consider early referral for transplant
evaluation in patients with decompensated
cirrhosis
Special Thanks
•
•
•
•
•
Mohamed Hassan
Coleman Smith
Julie Thompson
Jack Lake
Brad Benson
Questions?
[email protected]
Surgery in the Liver Patient
30 Day
Mortality by
MELD
Score
Teh, Swee H., et al. "Risk factors for mortality after surgery in patients with cirrhosis." Gastroenterology 132.4 (2007):
1261-1269.
Anticoagulation in the
Cirrhotic Patient
 Cannot assume auto-anticoagulation
 If bleeding risks are low the balance can shift to prothrombotic state.
 Anticoagulation may be safely managed in cirrhosis
 Case by case risk-benefit assessment required
4 am Cross-Cover Call: “Can I get a
Tylenol order for Mr. Johnson?”
• Acetaminophen at usual doses (650 mg orally, max 3
gm/d < 1 week) may be used safely in compensated
cirrhosis
• May give inpatient at 650 mg dose < 2 gm / 24 hrs for
short term use in more severe liver disease
2 am Cross-Cover Call:
“Lab called and the Na is 128”
• Common: 50% of hospitalized cirrhotics with
Na < 135, 20% < 130
• Associated with worse prognosis: MELD-Na
Hyponatremia in Cirrhosis
• Renal water retention >>
Sodium retention related to
SIADH
• Fluid restriction/ low Na diet
for most patients
– Minimally effective
• Reduction or d/c of diuretics
often required
• “Aquaresis” with vaptan
drugs available and
effective but EXPENSIVE
Optimizing oxygen delivery in the microcirculation:
Implications for blood transfusion
Erik B. Kistler, M.D., Ph.D.
Department of Anesthesiology & Critical Care
VA San Diego/University of California, San Diego
I have no disclosures
• Oxygen delivery (DO2) in health and critical illness
• The role of inspired oxygen in the microcirculation
• Implications for red blood cell transfusion in the microcirculation
O2 Delivery: DO2 = CO*CaO2
Arterial O2 content: CaO2 = SaO2*1.39*Hb + 0.0031*PaO2
DO2 = CO* (SaO2*1.39*Hb + 0.0031*PaO2)
Assumption: In critical illness inadequate O2 delivery to tissues is the problem (“cellular hypoxia”)
– If true, ↑DO2 should improve outcomes
Shoemaker WC, et al. Chest 1988; 94: 1176
Boyd, et al. JAMA 1993; 270:2699‐2707
Gattinoni L, et al. N Engl J Med, 1995;333(16):1025‐32
Hayes MA, et al. N Engl J Med 1994;330(24):1717‐22
Rivers E, et al. N Engl J Med 2001; 345(19):1368‐77
Al‐Khafaji A, et al. J Critical Care 2008; 23, 603–606
Macrocirculation and Goal Directed Therapy
Cellular hypoxia is thought to arise from:
Barcroft, J. Lancet II:485, Sept 4, 1920
å
å
Hypoxemia: ↓PaO2 – insufficient O2 inspired
å
Stagnation: ↓cardiac output – inadequate blood flow to carry O2 to tissues
Anemia: ↓hemoglobin – insufficient O2 transported
• ↓Microvascular perfusion
• Histotoxic: tissues cannot use O2, even if available
Histotoxic hypoxia
(Cytopathic hypoxia)
Organ dysfunction in critical illness at tissue and cell level
– Cells exhibit deranged (oxidative) function but don’t necessarily die (necrosis vs apoptosis)
– Organs may transition
to “hibernation state”
Fink MP. Crit Care. 2002;6(6):491‐9
Review of the vasculature
– Arteries: – Capillaries:
– Veins:
20% of circulating blood volume
5%
75%
– Capillaries contain greatest surface area (1200 m2 )
– Small arterioles are the most important determinants of vascular resistance
Tissue perfusion occurs at the microcirculation
Oxygen delivery
Krogh cylinder model: Assumption: all unloading of O2 occurs at the capillary bed along a longitudinal as well as radial gradient
PaO2 (mmHg)
100
80
60
40
20
Arteries Arterioles
Capillaries
Venules
Veins
Oxygen delivery
PaO2 (mmHg)
New model: Unloading of O2 predominantly at the arteriolar level
Nomenclature for microcirculation
Intaglietta, M, et al. Cardiovasc. Res. 32:632‐643, 1996.
Distribution of O2 in hamster skinfold preparation
Intravascular
Extravascular
Tissue PO2
~ 8‐20 mmHg
Minimum tissue PO2 needed probably ~ 2.3‐
2.8 mmHg
Safety Margin
O2 distribution at the vessel wall
60
Vessel lumen
PaO2 (mmHg)
50
40
Hamster skinfold
arteriole
O2 diffusion in tissue is limited:
30
Assuming ischemic threshold ~3‐5 mmHg, diffusion is limited to a maximum of 60‐70µm
20
10
10
Vessel wall
20
40
60
80
Distance from Vessel Wall (µm)
Why is there an O2 gradient at the vessel wall?
• High O2 consumption by arterioles and endothelium: Active metabolism – smooth muscle contraction
• ↑ venous PO2 necessary for metabolism, safety margin (?)
• Longitudinal differences depending on tissue studied:
– Brain: considerable longitudinal gradient, minimal arteriolar vessel wall gradient
– Skeletal muscle: less of a longitudinal gradient, greater arteriolar vessel wall gradient
What happens when supplementary oxygen is added to healthy tissue?
• ↑Oxygen extraction by vessel walls as they contract
• ↓Functional capillary density (FCD)
• ↑Shunting
• Is this to prevent O2
toxicity to tissues?
• Tissue PO2 may be “the” regulated variable
Wagner, P. Eur Respir J 2008; 31: 887–890
Schematic of Microcirculation
High PaO2 may limit O2 delivery to tissues
Limited shunting:
• O2 to venous circulation
• ‘safety feature’ : vasodilates with ↑PaO2, vasoconstricts with ↓PaO2
• regulates tissue O2?
Tissue perfusion in critical illness
Orthogonal polarization spectral imaging under the tongue (human)
Healthy volunteer
– BP 120/80
– SaO2 96%
Pt in septic shock after resuscitation with crystalloids/ colloid, ‘low dose’ dopamine
–
–
–
–
HR 82
BP 90/35
SaO2 98%
CVP 25mmHg
Taken from sepsis.com
Microcirculation in Sepsis
Capillary bed constricts (↓eNOS?)
This may be exacerbated by pressors
Shunt vasoconstriction is inhibited (↑iNOS?)
Microcirculation in Sepsis
DO2 = CO* (SaO2*1.39*Hb + 0.0031*PaO2)
DO2micro ≠ DO2
O2 consumption: VO2 ~ SvO2
↓FCD
Oxygen delivery in the microcirculation
Stokes flow
Highly nonlinear WBC sticking, RBC stiffening, Endothelial cell swelling
flow ~ dp/dx * 1/η↑
Hb ↓
Fahraeus effect
Saltzman DJ, et al. Microsurgery. 2013 Mar;33(3):207‐15
How can we ↑perfusion to the microcirculation?
Is it possible that ↑
FiO2 might make up for ↓ flow??
Changes in tissue oxygen tension
80
induced by hyperoxia at different Hcts
Hct 48%
60
Microvascular oxygen tensions at 21% FiO2
Hematocrict
Arteriolar
mmHg
Venular
mmHg
Tissue
mmHg
48% (BL)
48 ± 8
34 ± 6
21 ± 2
28%
51 ± 9
27 ± 6
20 ± 2
11%
30 ± 6
10 ± 4
2 ± 1
Values are means ± SD.
Hyperoxia induced change, %
40
20
0
‐20
Arteriolar
Venular
80
Tissue
Hct 28%
60
40
20
0
‐20
‐40
Arteriolar
Venular
Tissue
80
Hct 11%
60
40
20
0
↑FiO2 to 100%
‐20
Arteriolar
Venular
Tissue
Cabrales, P (2013)
Should we ↑FiO2 in critical illness?
• ↑FiO2 as necessary to achieve adequate SaO2
• ↑PaO2 delivered to tissues: – In anemia ‐ But total DO2 ↓
– In exercising muscle
• Note: CO from ~5 → 20 L/min
– Critical illness?
• Generally, NO
Focus should probably be on ↑perfusion not O2 per se Knight DR, et al. J appl Physiol. 81(1): 246‐251. 1996
Microcirculatory response to changing systemic Hb
Microvascular Hb
What is the relation between Hb in the systemic versus the microcirculation? Systemic Hb
Microcirculatory response to changing systemic Hb
Resistance to flow
HH Lipowsky and JC Ferril, AJP, 1986
Systemic Hb
HH Lipowsky and JC Ferril, AJP, 1986
Microvascular flow
Microcirculatory response to changing systemic Hb
Systemic Hb
Microcirculatory response to changing systemic Hb
DO2
HH Lipowsky and JC Ferril, AJP, 1986
Systemic Hb
HH Lipowsky and JC Ferril, AJP, 1986
O2 Delivery: DO2 = CO*CaO2
Arterial O2 content: CaO2 = SaO2*1.39*Hb + 0.0031*PaO2
DO2 = CO* (SaO2*1.39*Hb + 0.0031*PaO2)
How does changing these parameters affect “oxygen delivery” to the microcirculation?
Hb normal
Increase PaO2
Increase Hb
Increase CO
Hb = 7
Increase PaO2
Increase Hb
Increase CO
Hb = 7
14%↑ in DO2
Increase Hb
1U PRBC
Hb = 7
Increase Hb
Saugel et al. Scan J of Trauma, Resuscitation and Emergency Med 2013, 21:21
0.5 U
1 U
2 U
0.5 U
1 U
2 U
Tsai, et al 2014
Hb = 7
Increase Hb
Hb = 7
~3U PRBCs
Increase Hb
What explains this result?
DO2 = CO*(SaO2*1.39*Hb + 0.0031*PaO2) ??
But DO2 ≠ DO2micro
Calculated DO2micro after transfusion never achieves “normal” O2 delivery
Blood transfusion affects something other than Hb!
Inflammatory response!!
End‐result: ↓SVRmicro and ↑microvascular perfusion
Ramifications:
• >50% of blood transfused is in 1‐2 U PRBCs
• Non‐bleeding patients might be able to be effectively treated with fewer transfusions
• Novel blood substitutes improving microvascular flow (rather than O2 carrying capacity) could potentially be effective interventions.
Summary
• Macro‐vascular hemodynamics correlate only weakly with microvascular perfusion
• FiO2 > than necessary to maintain SaO2 is probably of limited efficacy except in low Hb states
• Transfusion with limited numbers of PRBC (<2 U) in non‐bleeding anemic patients is probably optimal
• Transfusion of ≤ 2U PRBCs ↑DO2micro >> predicted
Thanks!
Marcos Intaglietta Amy Tsai
Pedro Cabrales
Microhemodynamics Laboratory
Dept of Bioengineering
UC San Diego
Thanks
O2 distribution at the vessel wall
O2 measurement resolution:
• Palladium porphyrin phosphorescence quenching: 10 µm
• Tissue O2 probes: 250‐> 1000 µm
• Blood‐oxygen dependent (BOLD) fMRI: 1000‐5000 µm
• PET scan: >3000 µm
• NIRS > 10000 µm
60
Vessel lumen
PaO2 (mmHg)
50
40
30
Hamster skinfold
arteriole
O2 diffusion in tissue is limited: Assuming an ischemic threshold of ~3‐5 mmHg, under normal conditions diffusion is limited to a maximum of 60‐70µm
20
10
10
Vessel wall
20
40
60
80
Distance from Vessel Wall (µm)
Preload Optimization in Sepsis and
Other Hemodynamic Crises
53nd Annual Weil/UC San Diego Symposium on
Critical Care & Emergency Medicine
(April 11, 2015)
Raúl J. Gazmuri MD, PhD, FCCM
Resuscitation Institute
at Rosalind Franklin University
and
Captain James A. Lovell Federal
Health Care Center
(Section of Critical Care Medicine)
Conflicts
• Funding for research on various aspects of
resuscitation from cardiac arrest and
hemorrhagic shock and role of mitochondria
(DoD, VA Merit Review, Zoll, Baxter, Friends
Medical Research Institute, DePaul-RFU, and
ALGH)
• None related to the current presentation
Outline
• Definition of “preload optimization” and its
necessity
• Blood delivery is inadequate
• How to assess adequacy of blood delivery
• Clinical (signs of perfusion and organ function)
• Metabolic (lactate and SvO2, perhaps)
• Concept of preload
• How to assess and guide its optimization
• Upstream effects
PRELOAD OPTIMIZATION
• The concept of preload optimization
applies primarily to states of
inadequate blood delivery and
circulatory shock
• Circulatory shock can be defined as the
sustained failure to deliver and/or
utilize the oxygen required to meet
metabolic demands as a result of
circulatory (macro or micro) deficits
• Why is oxygen needed?
A
500 nm
B
C
100 nm
CYTOSOL
OMM
H+
H+
H+
H+
ADP
C
IMM
I
e-
Q
III
IIeNADH
H+
FADH2
H+
IV
O2
H+
ANT 180 mV
ATP
H2 O
ATP
ADP+Pi
MATRIX
+
FoF1 ATP
synthase
-
CYTOSOL
MITOCHONDRIA
Cr
ATP
ATP
ATP
CK
ADP
ATP
CK
CK
ADP
CK ATPase
ADP
pCr
Glycolysis
Cytosolic
ATP/ADP ratio
ADP
Cytosolic
ATP consumption
Oxidative
Phosphorylation
32 ATP
2 ATP
Some people may recognize the name, but few can comprehend how much this man has done for the fields of trauma and critical care. Dr. Weil was a world‐class clinician, teacher and researcher, and is believed to have coined the phrase “critical care medicine.”
Some of his many notable accomplishments:
In 1955, Dr. Weil created the first bedside shock cart, which is now known as the crash cart. In the late 1950’s, he and his colleagues recognized that some patients who were seriously ill or who had undergone major surgery had a propensity to die at night. He hit upon the concept that having an area for closer monitoring of these patients might allow for earlier recognition of acute problems and earlier intervention to correct them. This led to the creation of a four bed “shock ward.” This was the precursor to the first intensive care unit, which opened in 1968.
Introduced automated vital signs monitors in 1961.
Created the first computer assisted diagnosis tools in 1976.
Developed the STAT lab concept for rapid results in critically ill patients in 1981.
He was the co‐inventor for 22 patented devices including:
Resuscitation blanket to protect medical personnel from electric shocks when defibrillating patients (2002).
Capnometer for assessing the severity of shock which can be placed in the upper GI tract or under the tongue (2001).
The Weil Mini Chest Compressor (2006)
An IV pump system (1981), detection for occlusion or infiltration (1985)
Osmotic pressure sensor (1977)
High frequency ventilator (1983)
A method for identifying cardiac rhythm even while CPR is in progress (2006)
Dr. Weil established the Institute for Critical Care Medicine in 1961, and worked there full‐time after he left the University of Southern California. The institute trains physicians and engineers to discover and develop concepts and methods for more beneficial life‐saving medical management. He stepped down as the president of the institute in 2006, but continued to work there full‐time until two weeks before he died. The world has lost a true physician, teacher and innovator.
Max Harry Weil MD, PhD (Feb 9, 1927‐July 29, 2011)
2
̅
O2
CcO2
CvO2
2
10
2
10
CcO2
1.39
0.003
2
1.39
0.003
2
̅
2
2
̅
2
2
2
0.25
2
75
2
50
0.75
2
20 ml/dl 25
2
0
0
O2
2
SO2 (%)
100
CaO2
15 ml/dl
̅
2
25 50 75 100
pO2 (mmHg)
̅
2
2
2
2
1
2
2
̅
2
2
2
̅
2
20
1
0.25
15
2
20
1
0.75
5
Inability to consume oxygen (e.g., microcirculatory shunt)
20
1
0.25
15
SYSTEMIC OXYGEN DELIVERY
DO2 = CO x 10 x CaO2
AL
CO = HR x SVf
SV = EF x EDV
PL
CTR
CaO2 = 1.39 x SO2 x Hb + PaO2 x 0.003
2
ADEQUACY OF PERFUSION
 Bedside assessment of perfusion
 Reduced peripheral skin blood
flow (pulse, temperature, refill)
 Reduced urine output
 Tachycardia
 Hypotension (supine – orthostatic)
 Altered mentation
CARDIAC LOOP: DIASTOLIC DYSFUNCTION
mmHg
150
End of
systole
Diastolic
dysfunction
For a given enddiastolic volume
(preload), there is a
greater end-diastolic
pressure
50
End of
diastole
100 mL
50
CARDIAC LOOP: SYSTOLIC DYSFUNCTION
mmHg
150
End of
systole
Systolic
dysfunction
Dilation is
accompanied by
decreased compliance
and increased enddiastolic pressure
50
End of
diastole
50
100 mL
PRELOAD AUGMENTATION
Stroke Volume
Increased
contractility
Normal
Depressed
contractility
End Diastolic Pressure
TRANSMURAL PRESSURE
5 - (-1) = 6
5
9-5=4
12
9
-1
12 - 12 = 0
5
12
PRELOAD ASSESSMENT
• Fluid challenges are considered the
cornerstone for preload optimization
• However, not all hemodynamically unstable
patients are volume responsive
• Increasing evidence suggests that excess fluid
is associated with poor outcomes
• Thus, assessment of fluid responsiveness
might be appropriate before embarking on fluid
loading
• Static measurements (CVP, PAOP, IVC diameter,
LVEDA) may not be optimal for predicting
volume responsiveness
PRELOAD ASSESSMENT
• Bedside assessment of jugular veins
• Simple but requires skills; useful when
substantial volume deficit is present
correlates with IVC diameter and collapse
• Central venous pressure
• Poor correlation with RV preload and fluid
responsiveness
• Pulmonary artery occlusion pressure
• Similar limitations as CVP but useful to
titrate therapies
PRELOAD ASSESSMENT
• Passive leg raise
• Rapid (and reversible) translocation of 300 to 500 cc
of blood centrally
• LV stroke volume changes during mechanical
ventilation
• High sensitivity and specificity for fluid
responsiveness
• SVC and IVC diameter changes with
respiration
• High sensitivity and specificity for fluid
responsiveness
Passive Leg Rising
Alexander Levitov and Paul E. Marik. Cardiol Res Pract. 2012; 2012: 819696
IVC distensibility recorded with TTE during mechanical ventilation.
Alexander Levitov and Paul E. Marik. Cardiol Res Pract. 2012; 2012: 819696
Expiration
Inspiration
IVC collapsibility recorded with TTE in a spontaneously breathing patient.
Alexander Levitov and Paul E. Marik. Cardiol Res Pract. 2012; 2012: 819696
Early Goal-Directed Therapy in the Treatment of Severe
Sepsis and Septic Shock
Emanuel Rivers, M.D., M.P.H., Bryant Nguyen, M.D.,
Suzanne Havstad, M.A., Julie Ressler, B.S., Alexandria
Muzzin, B.S., Bernhard Knoblich, M.D., Edward Peterson,
Ph.D., and Michael Tomlanovich, M.D. for the Early GoalDirected Therapy Collaborative Group
N Engl J Med 2001; 345:1368-1377
Of the 263 enrolled patients, 130 were randomly assigned to
early goal-directed therapy and 133 to standard therapy; there
were no significant differences between the groups with respect
to base-line characteristics. In-hospital mortality was 30.5
percent in the group assigned to early goal-directed therapy,
as compared with 46.5 percent in the group assigned to
standard therapy (P=0.009).
H.J.C. "Jeremy" Swan
(1 June 1922 – 7 February 2005)
William Ganz
(January 7, 1919 - November 11, 2009)
Catheterization of the Heart in Man with Use of a Flow-Directed Balloon-Tipped
Catheter
H. J. C. Swan, M.B., Ph.D., F.R.C.P., William Ganz, M.D., C.Sc., James Forrester,
M.D., Harold Marcus, M.D., George Diamond, M.D., and David Chonette
N Engl J Med 1970; 283:447-451August 27, 1970
Pressures in the right side of the heart and pulmonary capillary wedge can
be obtained by cardiac catheterization without the aid of fluoroscopy. A No.
5 Fr double-lumen catheter with a balloon just proximal to the tip is inserted
into the right atrium under pressure monitoring. The balloon is then inflated
with 0.8 ml of air. The balloon is carried by blood flow through the right
side of the heart into the smaller radicles of the pulmonary artery. In this
position when the balloon is inflated wedge pressure is obtained. The
average time for passage of the catheter from the right atrium to the
pulmonary artery was 35 seconds in the first 100 passages. The frequency
of premature beats was minimal, and no other arrhythmias occurred.
From the Department of Cardiology, Cedars-Sinai Medical Center and the
Department of Medicine, University of California, Los Angeles
Hemodynamic Monitoring
Shock
RA
PA
PAOP
CO
Hypovolemic




Cardiogenic




Obstructive




Distributive




Starling’s Equation
• Net Flow = K[(Pc - Pi) + s(πi - π c)] - L
• K = membrane permeability
coefficient
• P = hydrostatic pressure
• π = colloid oncotic pressure
• s = Staverman reflection coefficient
• L = lymph flow
Case
• 76 year old male with multiple comorbidities
was found unresponsive with low O2 in the
medical floor and was transferred to ICU
• CXR showed right lower lobe pneumonia &
pleural effusion. Started on BiPAP and
treated with antibiotics & fluids
• Several days later hypercarbic acidosis on
BiPAP prompted intubation for mechanical
ventilation (PS 17, PEEP 5, FiO2 0.60)
• Peripheral edema and large right pleural
effusion noted; serum albumin 1.7 g/dl.
Case
• Thoracocentesis drained 2 liters of
transudate but patient remained on
mechanical ventilation
• CXR showed significant pulmonary edema
not responding to diuretics
• Recent echocardiography showed normal LV
size, walls, and systolic function, reversal of
E to A ratio, and estimated pulmonary artery
systolic pressure of <35 mmHg
• A pulmonary artery catheter was placed 4
days later
Case
Cardiac index was 3.5
l/min/m2, pulmonary
artery occlusive pressure
12-15 mmHg, diastolic
pulmonary artery
pressure 22 mmHg, and
systolic pulmonary artery
pressure 60 mmHg;
consistent with precapillary pulmonary artery
hypertension
Case
• Furosemide infusion started at 10 mg/h
monitoring pulmonary artery diastolic pressure
and cardiac index to avoid drop in preload
96 h
48 h
• prominent diuresis without hemodynamic
compromised PAOP 10-12 mmHg and CI 3.5-4.0
l/min/m2
Case
PofC‐5





Hypovolemic
Cardiogenic
Obstructive
Distributive
Combination
HEMODYNAMIC INSTABILITY
Goal: Hemodynamic Stability
Hemodynamic
Instability
Yes
Assess
Continue/Modify
Treatment
 Elevated Lactate (type A)
 Infusion Vasoconstrictive
Agent
 Skin/Kidney
Hypoperfusion





Preload
Cardiac Function
Vasoactive Drugs
Inotropic Drugs
Underlying Condition
Summary (II)
• Have a goal and reassess at
frequent intervals
• Exercise the various choices
available
• Develop and trust your team
• Measure outcomes and institute
new approaches as needed
Summary (I)
• Preload optimization and its necessity
• Blood delivery is inadequate
• Risk of fluid accumulation
• How to assess adequacy of blood delivery
• Clinical (signs of perfusion and organ function)
• Metabolic (lactate)
• Concept of preload
• Abnormalities in myocardial distensibility
• Upstream effects and safety factors
• Upstream effects to be avoided and treated
when they occur
MANAGEMENT OF
PATIENTS WITH ACUTE
EXACERBATION OF COPD
James Runo, MD
Pulmonary & Critical Care Medicine
University of Wisconsin-Madison
Financial Disclosures
• None related to this topic
Objectives
• Basic review on COPD including treatment
modalities
• Pharmacologic therapies for COPD
exacerbations
• Non-pharmacologic treatments for COPD
exacerbations
• Preventive measures
Definition of Acute Exacerbation
• Global Initiative for Chronic Obstructive
Lung Disease (GOLD) and WHO
– One or more of the following cardinal
symptoms
• Cough increases in frequency and severity
• Sputum production increases in volume and/or
changes character
• Increase in dyspnea
– Chest radiograph usually unchanged
Implications
•
•
•
•
•
Often occur 1-3 times per year
50% not reported to physicians
3-16% require hospitalization
Hospital mortality 3-24%
Need for ICU admission increases mortality to 1530%
• Adverse effects on functional status and QOL with
very slow recovery
• May contribute to accelerated loss of FEV1
Mortality after Hospitalization
49%
33%
Connors, AJRCCM 1996; 154:959
Risk Factors For Exacerbations
•
•
•
•
•
•
Advanced age
Severity of FEV1 impairment
Chronic sputum production
Frequent prior exacerbations
Hospitalization w/in past year
Comorbidities
– CAD
– CHF
– DM
Association of Disease Severity with the
Frequency and Severity of Exacerbations during
the First Year of Follow-up in Patients with COPD
Hurst, NEJM 2010; 363:1128
Differential Diagnosis
•
•
•
•
•
•
Pneumonia
Pneumothorax
CHF
Pulmonary embolism
Pleural effusion
Others
– Recurrent aspiration
– Upper airway obstruction
– Arrhythmia
Diagnostic Studies
• Chest radiography (for ED or hospital admits)
– 15-25% have abnormalities that will change rx
• Spirometry – not clinically useful
• ABG
– Mainly for hypercarbia assessment
• Sputum cultures
– Mainly for hospitalized patients
– Outpatient empiric therapy effective
•
•
•
•
+/- Respiratory viral PCR panel
BNP
D-dimer
Procalcitonin utility still unclear
Soler, Eur Respir J 2012; 40:1344
Thorax 2004; 59 (supp I)
Snow, Chest 2001; 119:1185
Etiology
• Infectious 80%
–
–
–
–
Bacterial 25-30%
Viral 25-30%
Co-infection 25-30%
Atypical bacteria 5-10%
• Noninfectious 20%
– Environmental exposures (NO2,
SO2, ozone, particulates)
– Noncompliance
Sethi, Chest 2000; 117 (suppl):380S
New Bacterial Strain Acquisition
• Sputum samples from 81 COPD (chronic
bronchitic) pts monthly and during exacerbations
• Performed molecular typing
• 1,975 clinic visits with 374 exacerbations
• Exacerbations occurred in 33% of clinic visits
with new isolate compared with 15.4% with
absence of new strain
• Relative risk for exacerbation with new strain 2.15
Sethi, NEJM 2002; 347:465
Sethi, S. Proc Am Thorac Soc 2004; 1:109
Admission Considerations
•
•
•
•
•
•
•
•
•
Comorbidities
Frequent exacerbations
Severe COPD
New Arrhythmias
Diagnostic uncertainty
Older age
Insufficient home support
Rapidly progressing or sudden onset symptoms
Failure of outpatient treatment
GOLD, AJRCCM 2007; 176:532
Worrisome Signs
•
•
•
•
•
•
•
•
Accessory muscle usage
Paradoxical respirations
Little or no air movement
Cyanosis
Peripheral edema
Hypotension
Signs of right heart failure
Altered mentation
Treatment Options
Removal of irritants
Corticosteroid therapy
•dust, pollutants,
cigarette smoke
•oral, IV, or inhaled
AE-COPD
Bronchodilators
-agonists,
anticholinergics
Antibiotics
Low-flow oxygen
Ventilatory support
Pharmacotherapy
Bronchodilators Reduce Hyperinflation
and Thereby Reduce Work of Breathing
Sutherland, NEJM 2004; 350:2689
β2-Agonist Agents
• Sympathomimetic activation through β2 receptors
in lung
• Side effects common
– Tremor
– Tachycardia
– Anxiety
• Albuterol sulfate
– 2.5 mg diluted in saline by nebulizer every 1-4 hrs
– 4-8 puffs by MDI every 1-4 hrs
• Oral agents not recommended due to systemic side
effects
Anticholinergic Agents
• Parasympathetic tone causes
bronchoconstriction at the level of the
smooth muscle cells
• Ipratropium bromide
• 0.5 mg by nebulizer q4hrs
• 2-4 puffs by MDI q4hrs
Combination Therapy More Effective
Test Day 85
40
% Change in mean FEV
1
Albuterol (N=165)
35
Ipratropium (N=176)
Ipratropium + Albuterol
(N=173)
30
25
20
15
10
5
0
0
2
1
3
4
5
6
Hours After Test Dose
7
8
Chest 1994;105:1411
Metered Dose Inhalers vs Nebulizers
MDI
Nebulizer
Metered Dose Inhalers
• Must be used with spacer device
for optimal drug delivery
• Shake canister
• At beginning of inspiration
actuate the MDI
• Breathe in slowly to full
capacity and hold 4-10 secs
• Wait 15-60 secs before next
dosage
Antibiotics in Acute Exacerbations
Overall Clinical Status
favors placebo
-1.0
favors antibiotics
-0.5
0
0.5
1.0
1.5
Effect size (SD)
Saint et al. JAMA. 1995;273:957
Antibiotics in Outpatient Setting
Sethi, Infect Dis Clin Am 2004; 18:861
Treatment Failures
32%
35
Relapse Rate (%)
• Retrospective analysis of
ED outpatient treatment of
362 exacerbations at a
VAMC
• 95% of severe episodes
were treated with Abx
• Relapse defined as return
visit w/in 14 days
30
25
19%
20
15
10
5
0
Abx
No abx
Adams, Chest 2000; 117:1345
Treatment Failures
Does choosing the correct antibiotic matter?
Relapse Rate (%)
60
50
40
30
20
10
0
Adams, Chest 2000; 117:1345
Antibiotic Summary
• Outpatient
– No Antibiotics
• Mild COPD exacerbation w/o sputum production
– Antibiotics
• Mod-severe COPD exacerbation
• Severe disease
• Low risk – doxycycline, bactrim, clarithromycin, azithro
– Avoid amoxicillin as not effective against most H. influenzae and M.
catarrhalis
• High risk – quinolone, augmentin, cipro (Pseudomonas)
– >65 yo, recent antbx, severe COPD, frequent exacerbations, cardiac dz
– 5-7 day duration
• Inpatient studies show antbx helpful
Corticosteroids
• No definitive evidence of improvement in
stable COPD patients
• Only indication is acute COPD exacerbation
– 40 mg/day for 5-7 days outpatient
– 5-14 days for inpatient
• Inhaled corticosteroids not indicated for
acute exacerbations
– May prevent exacerbations
Corticosteroids Improve Outcomes in
Outpatient COPD exacerbations
• Randomized 147 COPD
patients released from ER
to 10 days of placebo or
40 mg/day prednisone
• 10 days antibiotics
• Bronchodilators
• 30 day f/u with relapse
primary endpoint
Aaron, NEJM 2003; 348:2618
Corticosteroids Improve Outcomes in
Hospitalized COPD exacerbations
•
•
271 patients with acute COPD exacerbation admitted to VA hospitals
randomized to placebo, 2 weeks, or 8 weeks of prednisone therapy
Methylprednisolone 125 mg IV q6hrs x 3 days then taper from 60 mg/day oral
Niewoehner, NEJM 1999; 340:1941
Oral Versus Intravenous
• Retrospective study of 414 hospitals w/ AE-COPD, non-ICU
hospitalizations in 2006-7
• 79,985 pts total, 92% initial IV versus 8% oral
• Median total dose 1st 2 days – 600 mg IV vs 60 mg oral (prednisone)
• Hospital mortality 1.4% (IV) vs 1.0% (oral)
• Composite endpoint 10.9% (IV) vs 10.3% (oral)
– Mechanical ventilation after 2nd day, death, readmission for AE-COPD
w/in 30 days
• No differences after multivariable adjustments
• Lower failures, LOS, and cost in orals in propensity-matched analysis
Lindenauer, JAMA 2010; 303:2359
Methylxanthines
• Theophylline and Aminophylline
• Possible mechanisms
–
–
–
–
Bronchodilator
Improvement in diaphragmatic function
Respiratory stimulant
Pulmonary vasodilator and cardiac inotrope
• Narrow therapeutic window
– Keep levels in 8-12 ug/ml range
• Studies have failed to show benefit above that
obtained with bronchodilators and steroids
Hospitalized COPD Exacerbation
• High doses of β2-agonists
– Albuterol MDI 4-8 puffs q1-4 hrs or nebulizer
• Ipratropium
– MDI 2-4 puffs or nebulizer q4 hrs
• Corticosteroids (5-14 days)
– IV if severely ill, otherwise oral fine
• Antibiotics (5-7 days)
– Broad-spectrum IV if severely ill/pneumonia
• Antivirals if influenza suspected
• Hold on aminophylline/theophylline
Non-Pharmacologic
Therapies
Oxygen Therapy
• Only therapeutic intervention that
impacts mortality in COPD long-term
• Want to keep PaO2 60-70 mm Hg or
• SaO2 88-92%
• Never withhold oxygen due to CO2
concerns
Nocturnal Oxygen Therapy Trial
• 203 hypoxemic
COPD patients
• Randomized
nocturnal or
continuous oxygen
• Followed at least 1
year
• Mortality 1.94 times
higher in nocturnal
group
Ann Intern Med 1980; 93:391
Medical Research Council Study
• 87 COPD patients
with hypoxemia, CO2
retention, and CHF
• Randomized to
oxygen (> 15 hrs/d) or
not
• Mortality 45% vs
67%
Lancet 1981; 1:681
Oxygen’s Effects on PaCO2
• Oxygen therapy increased PaCO2 due to
– Worsened V/Q mismatch from pulmonary vasodilator
effect (reversal of hypoxic vasoconstriction)
– Haldane effect- increased SaO2 causes release of CO2
from Hb
– Slight decrease (15%) in minute ventilation (drive to
breath)
• Milic-Emili
– Am Rev Respir Dis 1980;122:191
– Am Rev Respir Dis 1980;122:747
Oxygen Parameters
• General
– PaO2 < 55 mm Hg or SaO2 < 88%
• In the presence of cor pulmonale
–
–
–
–
PaO2 < 59 mm Hg or SaO2 < 89%
ECG evidence of P pulmonale
Hct > 55%
Clinical right heart failure
• Air Travel
– General estimate is PaO2 > 70 mm Hg
– High altitude stimulation test (FiO2 = 0.15)
• Nocturnal amount should be same as needed for exercise
Chest Physiotherapy
• Chest percussion and vibration
• Intermittent positive pressure breathing
(IPPB)
• Postural drainage
• Bronchoscopy
• None have proven efficacy and may worsen
an exacerbation
Noninvasive Ventilation
• Biphasic positive airway pressure
(BiPAP) most effective
• Hypercarbia
• Pressure support 5-15 cm H20
• CPAP 3-5 cm H2O
• Allows time for pharmacotherapy to
work
15
Pressure
IPAP
Pressure support
5
CPAP/PEEP/EPAP
0
Time
Brochard, NEJM 1995; 333:817
Intubation occurred usually in 1st 12
hours in both groups
Brochard, NEJM 1995; 333:817
• More complications in control group
– 48% vs 16% (p = 0.001)
– More pneumonia
• Hospital LOS
– 35 days vs 23 days (p = 0.02)
• Mortality
– 29% vs 9% (p = 0.02)
• No difference in mortality after adjusting
for intubation
Brochard, NEJM 1995; 333:817
When to Use/Not Use NIPPV
• Selection criteria
– Mod-severe dyspnea w/ accessory muscle usage and/or paradoxical
abdominal motion
– Mod-severe acidosis (pH < 7.35) and/or hypercapnia (PaCO2 > 45 mm
Hg)
– Respiratory rate > 25
• Exclusion criteria
–
–
–
–
–
–
–
–
Respiratory arrest
CV instability (hypotension, arrhythmias, MI)
Poor mentation, uncooperative
High aspiration risk
Heavy secretions
Recent facial/gastroesophageal surgery
Craniofacial trauma or nasopharyngeal abnormalities
Burns
GOLD, AJRCCM 2007; 176:532
Intubation Criteria
• Unable to tolerate NIPPV or failure
• Severe dyspnea w/ usage of accessory muscles and paradoxical
abdominal motion
• Respiratory rate > 35
• Life-threatening hypoxemia
• Severe acidosis (pH < 7.25) and/or hypercapnia (PaCO2 > 60 mm Hg)
• Respiratory arrest
• Declining mentation
• Cardiovascular collapse (shock, arrhythmias)
• Other complications
– Metabolic abnormalities, sepsis, pneumonia, PE, barotrauma, massive pleural
effusion
GOLD, AJRCCM 2007; 176:532
Preventive
ICS Do Not Slow Disease
Progression
• 912 mild COPD patients
actively smoking
• Randomized placebo vs
800 mcg/d budesonide
• Initial improvement in
FEV1 with ICS but after 9
months slopes same
• End of 3 yrs placebo
group lost 180 ml and
ICS group lost 140 ml (P
= 0.05)
Budesonide Group
Placebo Group
Pauwels, NEJM 1999; 340:1948
ICS May Reduce Exacerbations and
Improve Symptoms
The Lung Health Study
ISOLDE Trial
• 1116 COPD pts
• Placebo or 1200 mcg
triamcinolone for 40 months
• No change FEV1 decline
• Fewer lung Sx’s (21.1 vs 28.2
per 100 person yrs)
• Fewer physician visits (1.2 vs
2.1 per 100 person yrs)
• Significantly lower BMD of
lumbar spine and femur
• 751 COPD pts
• Placebo or 1000 mcg
fluticasone for 3 yrs
• No change in FEV1 decline
• Median exacerbation rate
decreased by 25%
• Health status deterioration
significantly less
• Small but significant decrease
in serum cortisol levels
NEJM 2000; 343:1902
BMJ 2000; 320:1297
TORCH Trial
• 3 yr study of 6,112
COPD pts
• Reduction in
exacerbation rates for
LABA, inhaled steroid,
and combination
• Annual exacerbation
rate was 0.85 in combo
group and 1.13 in
placebo
• Higher pneumonia rates
with inhaled steroid
(alone and combo) and
mortality (inhaled
steroids alone, combo
lower)
Calverley, NEJM 2007; 356:775
Uplift Trial
• 5993 COPD pts given
Tiotropium or placebo for 4 yrs
• Improvement in FEV1 pre and
post bronchodilator maintained
for Tiotropium long-term
• No difference rate of FEV1 loss
• Quality of life improved
• Reduction in COPD
exacerbations
• No mortality difference (p =
0.09)
Tashkin, NEJM 2008; 359:1543
Tiotropium vs Salmeterol
• Tiotropium reduced risk of acute exacerbations in
moderate-severe COPD by 17% compared with salmeterol
Vogelmeier, NEJM 2011; 364:1093
Treatment Escalation
GOLD, AJRCCM 2007; 176:532
Azithromycin
• 1577 COPD pts randomized
placebo vs 250 mg/day azithro
• AE-COPD
– Azithro - 266 days 1st exacerbation,
1.48/yr
– Placebo – 174 days 1st exacerbation,
1.83/yr
• Hearing decline by audiograms
– 25% azithro, 20% placebo
• No cardiac differences
Albert, NEJM 2011; 365:689
Phosphodiesterase-4 Inhibitors
• Roflumilast – oral
PDE-4 inhibitor
• 1411 COPD pts
• 24 week trial
• Improved FEV1
• Trend for improved
symptoms
• Slight decline in
exacerbations
Rabe, Lancet 2005; 366:563
Pulmonary Rehabilitation
• Needs to have structured exercise training
w/wo educational classes
• Benefits wane over time
• Definite Improvements
– Dyspnea
– Exercise capacity
– +/- Reduced exacerbations
– Quality of life & Psychosocial
• No mortality or spirometry benefits
Vaccinations
• Influenza vaccinations
proven to prevent
acute respiratory
illness in COPD
patients
• Pneumococcal
vaccination should be
given to those with
COPD
Wongsurakiat, Chest 2004; 125:2001
Influenza Vaccination
• 10 year observational
study 1990-2000
• Elderly patients
– ~300,000 unvaccinated
– ~415,000 vaccinated
• 15-19% pts with lung dz
• 70%+ vaccination rate
• Results:
– 27% reduction admits for
influenza & pneumonia
– 48% reduction in risk of
death
Nichol, NEJM 2007; 357:1373
Pneumococcal Vaccination
• 596 COPD pts followed over 979 days and
divided whether received pneumococcal
vaccination (PV)
• Efficacy of PV in preventing infection
–
–
–
–
76% in pts < 65 yo (p = 0.013)
91% in pts < 65 with severe obstruction (p = 0.002)
48% in pts with FEV1 < 40% predicted (NS)
24% in all pt groups (NS)
Alfageme, Thorax 2006; 61:189
Age-related Decline in FEV1
FEV1 (% of value at age 25 y)
Never smoked or not susceptible to smoke
Stopped at 45 y
Stopped at 65 y
Smoked regularly and susceptible to its effects
100
75
50
Disability
25
Death
0
25
50
75
Age (y)
Tobacco Cessation
• Nicotine replacement
– Gum, patch, nasal, or inhaler
– Doubles quit rate
• Bupropion
– Seizure d/o contraindication
– Addition of nicotine little benefit
• Varenicline
– Partial agonist of nicotinic
acetylcholine receptors
– Superior quit rate than buproprion
– Insomnia and nausea
– Neuropsychiatric effects
Gonzales, JAMA 2006; 296:47
Psychiatric and Palliative Care
• Estimated 58% of COPD pts with psychiatric d/o
– 16% depression and 34% anxiety
– SSRI or bupropion
– Cautious usage of benzodiazepines
• Palliative care of dyspnea
– Oxygen therapy
– Narcotics best agents
– Benzodiazepines not effective
Yellowlees, Med J Aust 1987; 146:305
Lung Volume Reduction Surgery
• Resection of “nonfunctional” lung
• National Emphysema Treatment Trial (NETT)
– Mortality benefit for Upper Lobe disease and poor
exercise capacity after pulmonary rehab
– Worse mortality for FEV1 < 20% and either
homogenous dz or DLCO < 20%
– All others may receive symptomatic benefit
• Difficult to decide who to perform on
Fishman, NEJM 2003; 348:2059
Lung Transplantation
• Consider once
–
–
–
–
FEV1 < 25%
Hypoxemia/Hypercarbia
Pulmonary HTN
Rapid decline or
complications
• About 50% survival at
5 yrs with transplant
• Unclear if survival
advantage
Algorithm for Management of Patients With AE-COPD
Celli, B. JAMA 2003;290:2721
Assessment of Pulmonary Gas Exchange
and Adequacy of Systemic Oxygen delivery
53nd Annual Weil/UC San Diego Symposium on
Critical Care & Emergency Medicine
(April 11, 2015)
Raúl J. Gazmuri MD, PhD, FCCM
Resuscitation Institute
at Rosalind Franklin University
and
Captain James A. Lovell Federal
Health Care Center
(Section of Critical Care Medicine)
Conflicts
• Funding for research on various aspects of
resuscitation from cardiac arrest and
hemorrhagic shock and role of mitochondria
(DoD, VA Merit Review, Zoll, Baxter, Friends
Medical Research Institute, DePaul-RFU, and
ALGH)
• None related to the current presentation
A
500 nm
B
C
100 nm
CYTOSOL
OMM
H+
H+
H+
H+
ADP
C
IMM
I
e-
Q
III
IV
IIeNADH
H+
H+
O2
FADH2
H+
+
ANT 180 mV
-
ATP
H2 O
ATP
ADP+Pi
MATRIX
FoF1 ATP
synthase
CYTOSOL
MITOCHONDRIA
Cr
ATP
ATP
ATP
CK
ADP
ATP
CK
CK
ADP
CK ATPase
ADP
pCr
Glycolysis
Oxidative
Phosphorylation
Cytosolic
ATP/ADP ratio
ADP
Cytosolic
ATP consumption
32 ATP
2 ATP
SYSTEMIC OXYGEN DELIVERY
DO2 = CO x 10 x CaO2
AL
CO = HR x SVf
SV = EF x EDV
PL
CTR
CaO2 = 1.39 x SO2 x Hb + PaO2 x 0.003
MEASURING OXYGEN CONTENT
CaO2 = 1.39 x SO2 x Hb + PaO2 x 0.003
0.97
18.9
98
0.3
100
75
SO2 (%)
19.2 ml/dl
14
50
25
0
0
25
50
75
pO2 (mmHg)
100
MEASURING OXYGEN CONTENT
Functional O2 saturation
O2Hb
SaO2 % =
x 100
O2Hb+HHb
Fractional O2 saturation
O2Hb % =
O2Hb
O2Hb+HHb+COHb+MetHb
x 100
SYSTEMIC OXYGEN DELIVERY
CaO2 = 1.39 x SO2 x Hb + PaO2 x 0.003
100
SO2 (%)
75
50
25
0
0
25
50
75
pO2 (mmHg)
100
OXYGENATION OF ARTERIAL BLOOD
Alveolar Gas Equation
PAO2 = FiO2 x (PB-PH2O) - PaCO2/RQ
0.21
760 - 47
40/0.8
100
75
SO2 (%)
99.7
50
25
0
0
25
50
75
pO2 (mmHg)
100
OXYGENATION OF ARTERIAL BLOOD
100
75
SO2 (%)
Alveolar Gas Equation
PA-a O2 gradient = 10 mmHg
50
25
0
0
25
50
75
pO2 (mmHg)
100
Normal
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
0.21
760 - 47
40/0.8
PaO2
99.7
89.7 (96.8)
OXYGENATION OF ARTERIAL BLOOD
100
75
SO2 (%)
Alveolar Gas Equation
PA-a O2 gradient = 10 mmHg
50
25
0
0
25
50
75
pO2 (mmHg)
100
Low FiO2 + Hyperventilation
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
PaO2
0.12
760 - 47
40/0.8
35.6
25.6 (47.2)
0.12
760 - 47
20/0.8
60.6
50.6 (93.5)
OXYGENATION OF ARTERIAL BLOOD
100
75
SO2 (%)
Alveolar Gas Equation
PA-a O2 gradient = 10 mmHg
50
25
0
0
25
50
75
pO2 (mmHg)
100
Mount Everest + O2
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
0.21
236 - 47
40/0.8
1.00
236 - 47
40/0.8
-10
PaO2
-10
138.9 128.9 (98.5)
OXYGENATION OF ARTERIAL BLOOD
100
75
SO2 (%)
Alveolar Gas Equation
PA-a O2 gradient = 10 mmHg
50
25
0
0
25
50
75
pO2 (mmHg)
100
Mount Everest + Hyperventilation
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
PaO2
0.21
236 - 47
40/0.8
-10
-10
0.21
236 - 47
12/0.8
25
15
OXYGENATION OF ARTERIAL BLOOD
100
75
SO2 (%)
Alveolar Gas Equation
PA-a O2 gradient = 10 mmHg
50
25
0
0
25
50
75
pO2 (mmHg)
100
Acute Hypercarbia + O2
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
PaO2
0.21
760 - 47
80/0.8
49.7
39.7 (56.4)
0.30
760 - 47
80/0.8
113.9 103.9 (95.5)
OXYGENATION OF ARTERIAL BLOOD
100
75
SO2 (%)
Alveolar Gas Equation
PA-a O2 gradient = 10 mmHg
50
25
0
0
25
50
75
pO2 (mmHg)
100
Chronic Hypercarbia + O2
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
PaO2
0.21
760 - 47
90/0.8
37.2
27.2 (43.9)
0.30
760 - 47
80/0.8
101.4
91.4 (95.9)
OXYGENATION OF ARTERIAL BLOOD
100
Alveolar Gas Equation
PA-a O2 gradient = 40 mmHg
SO2 (%)
75
50
25
0
0
25
50
75
pO2 (mmHg)
100
OXYGENATION OF ARTERIAL BLOOD
100
Alveolar Gas Equation
PA-a O2 gradient = 60 mmHg
SO2 (%)
75
50
25
0
0
25
50
75
pO2 (mmHg)
100
V/Q mismatch + O2
FiO2 x (PB-PH2O) - PaCO2/RQ = PAO2
PaO2
0.21
760 - 47
40/0.8
99.7
0.40
760 - 47
40/0.8
235.2 175.2 (99.2)
2
̅
O2
CcO2
CvO2
2
10
2
10
CcO2
1.39
0.003
2
1.39
0.003
2
̅
2
2
̅
2
2
2
0.25
2
75
2
50
20 ml/dl 25
2
0
2
0
O2
2
SO2 (%)
100
CaO2
15 ml/dl
̅
2
39.7 (73.8)
25 50 75 100
pO2 (mmHg)
0.75
̅
2
2
2
2
1
2
2
̅
2
2
2
̅
2
20
1
0.25
15
2
20
1
0.75
5
Inability to consume oxygen (e.g., microcirculatory shunt)
20
1
0.25
15
2
2
O2
CcO2
2
2
1
̅
2
̅
2
̅
2
2
20
1
0.25
15
20
1
0.50
10
20
1
0.75
5
50
25
0
2
O2
25 50 75 100
pO2 (mmHg)
2
1.39
SO2 (%)
100
CcO2
0.003
2
2
10
2
10
2
2
̅
75
CaO2
2
50
25
CvO2
0
2
0
2
O2
25 50 75 100
pO2 (mmHg)
2
2
2
1
2
2
2
SO2 (%)
100
CcO2
̅
2
2
2
̅
2
20
1
0.25
15
20
1
0.50
10
20
1
0.75
5
75
CaO2
50
25
CvO2
0
0
2
O2
25 50 75 100
pO2 (mmHg)
2
1.39
SO2 (%)
100
CcO2
0.003
2
2
10
2
10
2
2
̅
75
CaO2
2
50
25
CvO2
0
2
0
2
25 50 75 100
pO2 (mmHg)
1
2
2
2
75
50
25
0
0
2
2
2
SO2 (%)
100
CaO2
̅
2
2
2
̅
2
CvO2
2
2
2
2
0
CvO2
̅
2
75
CaO2
CcO2
2
2
2
2
̅
CvO2
O2
2
̅
2
25 50 75 100
pO2 (mmHg)
SO2 (%)
100
CcO2
CvO2
10
0
2
CvO2
2
20 ml/dl 25
0
CvO2
2
10
50
O2
CvO2
0.003
2
75
CaO2
15 ml/dl
1.39
SO2 (%)
100
CcO2
CvO2
2
25 50 75 100
pO2 (mmHg)
20
1
0.25
15
20
1
0.50
10
20
1
0.75
5
CAPNOMETRY IN SUSPECTED PULMONARY EMBOLISM
WITH POSITIVE D-DIMER IN THE FIELD
Crit Care. 2009; 13(6): R196
Patients total
131
No 31
PETCO2 > 28 mmHg and
low clinical probability is a
potentially safe method for
excluding PE in patients
with suspected PE and
positive D-dimer test
Inclusion criteria
Di-dimer +
Yes 100
Clinical probability of PE (Wells criteria)
Unlikely 55
PETCO2
nasal
> 28 mmHg < 28 mmHg
35
20
PE 0
PE 14
Likely 45
> 28 mmHg < 28 mmHg
17
28
PE 3
PE 24
The combination of
PETCO2 < 28 mmHg and
high clinical probability is
a potentially safe method
for confirmation of PE in
patients with suspected
PE and positive D-dimer
SUMMARY
•
Oxygen is required to sustained electron transport at
the mitochondrial levels; which provides the energy
for establishing the proton-motive force that drives
ATP synthesis
•
Oxygen delivery is function of cardiac output and
arterial oxygen content
•
Most of the oxygen travels bound to hemoglobin and
therefore measuring the % of oxygen bound to
hemoglobin is more important than measuring PaO2
(SpO2)
•
Because hemoglobin uptakes oxygen as blood passes
through the pulmonary capillaries, knowing the
alveolar gas equation helps determine mechanism of
hypoxemia
SUMMARY
•
Widening of the alveolar-arterial oxygen gradient
caused by areas of low V/Q or zero V/Q (shunt) –
venous admixture – is a common mechanism of
hypoxemia
•
The oxygen content of venous admixture – which is
determined by tissue oxygen extraction – influences
arterial oxygen content
•
Mechanical ventilation with use of PEEP is intended to
reduce venous admixture
•
•
When PEEP fails, VV-ECMO should be considered.
Identification of areas of dead space ventilation (high
V/Q) could be useful in the diagnosis of pulmonary
embolism.
4/11/2015
Starting a Sepsis Program
Practice, Politics and Performance
Emanuel P. Rivers, MD, MPH
Vice Chairman and Research Director
Emergency and Surgical Critical Care Medicine
Henry Ford Hospital
Clinical Professor, Wayne State University
Detroit, Michigan
Institute of Medicine, National Academies
The Size of the Problem
1
4/11/2015
HealthGrades analyzed over 5 million Medicare
records of patients admitted through the emergency
department at 4,907 hospitals from 2006 through
2008, to identify the top 5% of the best-performing
hospitals in emergency medicine.
Changing the Landscape of Sepsis
Diagnosis and Treatment
2
4/11/2015
Pre-Hospital
ICU
General IPD Floors
ED
•
•
•
•
•
115 million visits/year.
2.9% of hospital admits are
severe sepsis and septic shock.
– 600,000 admissions per
year through the ED.
ED waiting times (5-6 hours)
approaching 24 hours.
•
67 minute delay to
ICU arrival.#
3 fold increase in
mortality.
After ICU Admission:
– 2 hour delay for PA catheter*
– > 6 hour total delay for
hemodynamic optimization.
•
Shock outcome:
– ICU - 24%
– ED or GPU - 70%.
McCaig: MMWR, 2001, Angus DC et al. CCM, 2001,
Varon, CCM, 1997, Lundberg, 1998, CCM, Lefrant, 2000*, CCM
How can I do this at my Hospital?
The Problem:
Changing The Current Paradigm
3
4/11/2015
Cases per year Mortality (%)
Sepsis
859,858
15-20
Severe Sepsis
791,000
27-40
Septic Shock
200,000
36-47
Pneumonia
1,187,180
5-9
Stroke
591,996
6-7
Acute Myocardial Infarction
540,891
10
Trauma
697,025
5-16
Time Sensitive Diseases
Changing the Paradigm of Practice
AMI
Stroke
Trauma
< 10%
8-25%
< 5%
4
4/11/2015
Developing a program is not
as painful as it seems!
5
4/11/2015
Make it Entertaining
Fear?
Castor Bean
Ricin
Bacillus
Anthracis
Ebola
6
4/11/2015
Disaster Planning
215,000 Deaths/Year
A Sepsis Pilot
• Recognizes trouble before it starts
• Follows standard operating
procedures (SOP) for managing
sepsis.
• Does not take little things for granted.
• Understands the consequences:
– Immediate
– Long term
• Holds everyone accountable
– takes personal responsibility for
outcomes.
7
4/11/2015
The Devil is in the Details of a Sepsis Program
Epidemiology
3 Concepts
Understanding
the
Pathogenesis
6 hour
of
Documentation
and
Bundle
Teams
Standard Operating Procedures
Recognizing
one has a
problem?
Early Staging
of Illness
Severity
Timely
Interventions
Upon Arrival
Definitive
Care
ED or ICU?
Current Sepsis
Management
Early Markers
24 hour
Bundle
Documentation
And Orders
NAME
5 Page Order Set
Quality
Assurance
Improved
Outcomes
And Costs
CME
and
Peer
Uniformity
DRAFT
PORTER
INSULIN INFUSION PROTOCOL FOR THE INTENSIVE CARE UNIT
ACCT #
NAME:
ACCOUNT #:
PORTER
Item # 12339
Form # 645014
Revised 1/2006
SEVERE SEPSIS MANAGMENT
Corticosteroids
ITEM # 13081
PORTER
XIGRIS (DROTRECOGIN
ALFA) PROTOCOL
DATE:
Name:
Acct #:
Date:
REVISED 4/05
GENERAL CONSIDERATIONS
Insulin
Rev 1/05
infusion will be considered if a patient is in the Intensive Care Unit (ICU) and blood sugar is greater than 110 mg/dl.

The insulin infusion will be titrated to maintain the blood glucose levels in the range of 80-110 mg/dl.

Intensive Insulin Protocol is to be discontinued on discharge from the ICU.

All IVPBs
in 0.9%
when
possible.
FOR
USENSIN
CRITICAL
CARE AREAS ONLY

Maximum infusion rate is 50 units per hour.
PREPARATION OF IV INSULIN INFUSION
F orm #730022

Item #11909
ROOM #:
DATE
PORTER
NAME:
ACCOUNT #:
FORM # 640012
ROOM #:
PHYSICIAN ORDERS
IMPORTANT: PLEASE USE BALL POINT PEN

Infusion should be mixed at a concentration of 1 unit of regular insulin per ml of 0.9% NS
SEVERE SEPSIS MANAGEMENT
Corticosteroids
 and
Infuse
intomanage
an IV line using an infusion pump to control the rate.
The prescribing of Xigris is limited
to those
knowledgable
its use and in the care of critically ill patients with sepsis
who
Early
Goal
Directed inTherapy
Screening for Severe Sepsis:
Room #:
NAME:
ACCOUNT #:
mechanical ventilation. This therapy is to be initiated only in a critical care unit or in a patient waiting to be transferred
GLUCOSE
toMONITORING
a critical care unit.
DURING IV INSULIN INFUSION
11. Any other condition in which bleeding
a significant
hazard
 constitutes
Blood glucose
monitored
Patient
every
meets
1 hour
the on
three
initiation
following
and aftercriteria
a rate change.
Xigris Therapy Inclusion
ITEM # Criteria:
13080
FORM # 640011
REVISED
4/05
Inclusion
criteria
or would be difficult to manage because of its
location
Blood
glucose
monitored
every
2 hours
glucose level is between 80-110 mg/dl
SIRS
Criteria:
Two
or more
ofonce
the blood
following
 Suspect
infection
12. Age
less than 18 years

Blood glucose
monitored
hoursorif greater
glucose level
 Temp
lessevery
than496.8
thanremains
100.4 between 80-110 for 24 hours
13. criteria
Pregnant
breastfeeding
 SIRS
(3orout
of 4)
 poorly
Bloodcontrolled
glucose
monitored
PRN
14. Uncorrectable
condition (e.g.
 HR
neoplasm
greater
orthan or equal to 90
 Patient
is receiving medical
vasopressors
other end-stage disease)
 RR
greater than or equal to 20, or PCO2 less than 32
 Patient
is mechanically ventilatedcount of less than
3 DRIP
OF INSULIN
15. HIV in association with a CD4 INITIATION
50/mm
 WBC less than 4,000 or greater than 12,000
Cosyntropin16.Stimulation
Testlung, Iiver, pancreas
Bone marrow,
BloodorGlucose
small bowel transplantation
Insulin infusion rate
 Perforated viscus
#: ITEM # 13079 FORM # 640010 REVISED 4/05
 Bands
greater than 10%
17. Chronic
renalCortisol
failure requiring
hemodialysis
or peritoneal
dialysis
 Baseline
Random
level Greater
than 110
mg/dl
Initiate insulin infusion @ 2 units per hour
18. Recent250
(within
7 days)
toSystem
increaseFailure:
the risk One or more of the following
PHYSICIAN ORDERS Modified SIRS Criteria
FOR(Three
USEorIN
CRITICAL
CARE AREAS
Organ
 ONLY
Cosyntropin
mcg
IVP use of medications
Greater than known
220
mg/dl
Initiate insulin infusion @ 4 units per hour
more
of the following):
of
bleeding
including
aspirin,
NSAIDS,
COX-2
inhibitors,
clopidogrel
Temp less than or equal to 96.8F or greater than or equal to
 level
Respiratory
 Random
cortisol level 30 minutesIfand
next60
blood glucose
is between 110-140 mg/dl
Increase insulin infusion rate by 1 unit per hour
(Plavix), ticlopidine (Ticlid), and cilostazol (Pletal)
100.4F
IMPORTANT: PLEASE USE BALL POINT PEN
If next blood
glucose
level
Cardiovascular
is greater than 140 mg/dl
Increase insulin infusion rate by 2 units per hour
minutes
after cosyntropin
19. Concurrent
use of anyadministration
of the following
treatment
regimens:
HR greater than or equal to 90 bpm
OF INSULIN
a. treatment
doses after
of unfractionated

Renal
than orDRIP
equal
and Florinef
60MAINTENANCE
minute heparin (greater
Early Goal Directed Therapy Resp rate greater than or equal to 20 bpm or PaCO 2 less than Start Hydrocortisone
to 15units/kg/h) or until aPTTreturns
to baseline
Check
blood
within 60 minutes of starting insulin infusion and titrate according to table below. Use the lower rates for patients
 glucose
Hematologic
Screening for Severe Sepsis:
cortisol level is drawn
or equal to 32mmHg
Inclusion Criteria
3
b. treatment doses of enoxaparin (Lovenox)
withinglucose
hours
before
is decreasing
rapidly (greater than 30mg/dl); the higher rate for those decreasing slowly (less than 30mg/dl). Infusion
WBC less than or equal to
4,000/mm
or greater
than following
or equal
 12
Metabolic
 Hydrocortisone
mg IVP every 6 hours whose blood
Patient
meets
the three
criteria
 Suspect infection
Xigris50
infusion
may be titrated in increments of 0.5 units/hour.
to 12,000/mm3 or greater than 10% bands
 Hepatic
 Florinefc.50 treatment
mcg PO/NG
every
day (Angiomax), lepirudin
SIRS Criteria: Two or more of the following
doses
of bivalrudin
(Refludan)
SIRS
(2 out of 4)
FORUSE
INcriteria
CRITICAL
CARE AREAS ONLY
Blood Glucose
Insulin Infusion Rate
Argatroban
4 hours before Xigris infusion
 CNS
or until
(altered
aPTTlevel of consciousness)
Stop hydrocortisoneorand
florinefwithin
if cortisol
Temp
lessone
than
than 100.4
 SBP less than 90 mmHg after Organ
2-3 liters
of FailureCriteria
System
(Any
or 96.8
moreor
ofgreater
the following):
Stop insulin infusion and administer 25 ml dextrose 50% and check blood glucose in 1 hour.
Less than
returns
to baseline
change is greater than
or equal
to 9
Sepsis-induced
 respiratory
HR greater
distress
than or
syndrome
equal torequiring
90
IMPORTANT:
fluid
PLEASE USE BALL
POINT PENacute
Infection:
Onethan
or
more
If greater
or
equaloftothe
80,following
resume infusion @ 50% of previous rate. If less than or equal to 80 recheck blood glucose in 1 hour.
60 mg/dl
d. warfarin, if INR is elevated due
to warfarin use,
warfarin
should
mechanical
ventilation
Continue
and florinef
for INR
761-79
days
 RR greater than or equal to 20, or PCO2
less thanhydrocortisone
32
 Lactate level greater than 4
 Documented
Decrease infusion by 50% and recheck glucose in 60 minutes.
mg/dl
be discontinued
and the
should
be rev ersed
prior to starting
Septic shock requiring vasopressors despite fluid resuscitation
if Cortisol change isXigris
less than 9
 WBC less than 4,000 or greater than 12,000
No change.
 Place
Venous
O 2 Catheter Any 2 sepsis-induced
80-110 mg/dl
 Anti-infective therapy
dysfunctional organs
Screening
forCentral
Severe
Sepsis:
e. thrombolytic therapy within
3 days mg/dl
(excluding
for catheter
greater than 10%
increase infusion by 0-1 units/hour
111-150
 Place arterial line
usePneumonia
  Respiratory Bands
Cardiovascular
Patient meets the three following
criteria
clearance) before Xigris infusion
151-180 mg/dl  WBCs
increase infusion by 0.5-1.5 units/hour
  RenalOrgan SystemHematologic
Fluid replacement:
Failure: One or more of the following
f.
glycoprotein IIb/IIIa antagonists within 7 days
before Xigris
SIRS Criteria: Two or more of the following


Metabolic
Hepatic
181-200
mg/dl
increase
infusion
by 1-3 units/hour and bolus with 2 units
CVP of less than or equal to 8
 Perforated viscus
 Respiratory
infusion.
100.4
CNS (altered level of consciousness)
 Temp less than 98.6 or greater 
than
201-250 mg/dl
increase infusion by 1-3 units/hour and bolus with 4 units
 500 ml bolus of 0.9% sodium
chloride
 Cardiovascular

 Patient is not a candidate increase
for corticosteroids.
 HR greater than or equal to 90
251-300 mg/dl
infusion by 1-3 units/hour and bolus with 6 units
every 30 minutes
Renal
Patient IS a candidate for Xigris therapy. Proceed with administration. 
Xigris should be startedwithin
the first 24 hours of the first sepsisGreater than
Notify physician
 RR
greater
than
or fluid
equalreplacement
to 20,induced
or PCO2
less than 32 Hematologic

MAP
less
than 65
after
organ dysfunction.
300
mg/dl due to :
 
WBC
less than 4,000
greatercc,than
12,000
Patient IS NOT a candidate for Xigris
therapy
Norepinephrine
16 or
mg/250
titrate
to
 Metabolic
_______________________________________________________
 Bands greater than 10%
Contraindications to the Use of Xigris (per package insert):
PORTER
Infection Criteria (One or more of the following):
Documented
Anti-infective therapy
SEVERE SEPSIS MANAGEMENT
 Pneumonia
Early Antibiotics
 WBCs
ROOM
DATE
ROOM #:
DATE
PHYSICIAN ORDERS
Inclusion Criteria
 SIRS criteria (2 out of 4)
 Organ System Failure (1 or more)
 Infection (1 or more)
Cultures (prior to antibiotic administration):
 Blood cultures
 UA C & S
 Sputum gram stain, C & S
 Wound C & S
Early antibiotics (initial regimen should include 1
antibiotic from all 3 groups A, B, C):
A: Gram Negative Rod coverage (choose one)
 Piperacillin/tazobactam (Zosyn) 3.375 g
IVPB every 6 hours
 Imipenem/cilastatin (Primaxin) 500 mg
IVPB every 6 hours
 Aztreonam (Azactam) 2 gram IVPB every 8
hours (for Penicillin allergy only)
B: MRSA coverage (choose one)
 Vancomycin 1 gram IVPB every 12 hours
 Linezolid (Zyvox) 600 mg IVPB every 12
hours
C: Quinolone or Aminoglycoside (choose one)
 Gentamicin 5 mg/kg IVPB every day
 Amikacin 15 mg/kg IVPB every day
 Levofloxacin 750 mg IVPB every day
 De-escalate initial antibiotic regimen at 72 hrs
1) No MRSA – DC Vancomycin/Zyvox
2) No MDR pseudomonas – select
appropriate regimen based on culture data or
clinical setting.
*Pharmacy will follow for antibiotic dosing
maintain a MAP equal to 65
 Hepatic
SPECIAL CONCERNS
1. Active internal bleeding
MAP greater than 90
 CNS (altered level of consciousness)

If the patient leaves the ICU without an ICU RN present, DC protocol and resume when patient returns to the ICU.
(within 3 months) hemorrhagic stroke
Organ System Failure: One or more of 2.
theRecent
following
Medication Order
 Nitroglycerin 50 mg/250 cc,3.titrate
to (within 2 Infection:
One or or
more
of the surgery,
following

When tube feeding or TPN infusions are briefly interrupted, start D 10W @ 50cc/hr and continue to titrate the drip as above.
Recent
months) intracranial
intraspinal
or severe
 Respiratory
Patient Wt:___________________________ (Please fill in)
maintain a MAP equal to 90head trauma

Discontinue the protocol when the patient resumes a P.O. diet.
 Documented
 Cardiovascular
4. Trauma with an increased
of life-threatening
bleeding
ScvO2 less than 70

Call physician for orders in patients with increased ICP.
 risk
Anti-infective
therapy
IV Infusion Administration
 Renal
of an epidural catheter
When
insulinweighing
infusion is
stopped for a non-protocol interruption, follow “INITIATION OF INSULIN DRIP” when resumed.
Dobutamine 500mg/250 cc 5.
IV,Presence
start at 2.5
Pneumonia
1. Mix drotrecogin alfa 10mg in 125mL0.9%NS
forthe
patients
less
6. Intracranial neoplasm 
or mass
lesion or evidence of cerebral herniation
 Hematologic
 0.9%NS
Insulin requirements
may increase in patients receiving glucocorticoids or IV vasopressors.
mcg/kg/min, increase by 2.5 mcg/kg/min
than 154 pounds (70kg) or 20mg in 250mL
for patients weighing
 WBCs
 Metabolic
o shake.
When weaning vasopressors, check blood glucose every 30-60 minutes depending on the rate of weaning.
greater than or equal to 154 pounds (70kg). Do not
every 30 minutes until ScvO2
greater to the Use 
Precautions
of Xigris
(per package
Perforated
viscusinsert and Prowess
2.
Infuse
through
a
dedicated
central
line
at
a rate of 24 mcg/kg/hour x 96
 Hepatic
study of
criteria):
than or equal to 70, or maximum
20
hours total
3
 Patient
notisaincreased
candidate
Early Goal Directed
Physician Signature:________________________________________________
Date/Time: _______________________________
 CNS
(altered level of consciousness)
1. Plts less than 30,000/mm
, even ifiscount
afterfor
transfusions
mcg/kg/min.
3. If any bleeding occurs during infusion, stop infusion and inform
White – Chart
Canary - Pharmacy
2.
PT-INR
greater
than
3,
aPTT
greater
than
100
Infection: One
or Dobutamine
more of the following
Therapy.
Hold
if:
physician immediately
3. Recent (within 6 weeks) GI bleeding
 Documented
4. Note any time that infusion is interrupted and restarted. When infusion
 Heart rate greater than 120
4. Recent (within 3 months) ischemic stroke
is
restarted,
resume
at
rate
of
24mcg/kg/hour.
Dose
escalation
or
bolus
 Anti-infective therapy
5. Intracranial AVM or aneurysm
 MAP less than 65 on nor-epinephrine
 Pneumonia
6. Known bleeding diathesis
PHYSICIAN doses are not recommended.
DATE/TIME
5. Stop Xigris infusion 2 hours prior to undergoing any invasive surgical
 If hematocrit less than 30%,
transfuse
7. Chronic
severe hepatic disease
 WBCs
SIGNATURE: procedure or procedure with an inherent risk of bleeding. Once adequate
8. Acute pancreatitis with no established source of infection
PRBC
 Perforated
viscus
hemostasisWHITE:
has been achieved,
be reconsidered
12
CHART initiation of Xigris may
CANARY:
PHARMACY
9. Patient with suspected meningitis and plts less than 45,000/mm 3
 Measure lactate level in 4 hours
hours after major invasive procedures or surgery or restarted immediately
10. Surgery with general or spinal anesthesia within 12 hours before
Xigris infusion or the potential need for such surgery during infusion
Date / Time:
White - Chart
PHYSICIAN
SIGNATURE:
Canary - Pharmacy
DATE/TIME
WHITE: CHART
PHYSICIAN
SIGNATURE:
after uncomplicated less invasive procedures.
6. A prepared Xigris infusion is stable for 12 hours refrigerated and an
additional 12 hours at room temperature.
Physician Signature:
CANARY: PHARMACY
DATE/TIME
WHITE: CHART
CANARY: PHARMACY
Early Identification
8
4/11/2015
Annal of Surgery 2010
9
4/11/2015
15 - 40 Fold Increase in Mortality
10
4/11/2015
Risk Stratification or Early
Detection of High Risk Patients:
The Evidence for the
use of Lactate
11
4/11/2015
Risk Stratification of Sepsis
–Hypotension, vasopressors:
–Lactate > 4 Only:
–SBP < 90 and Lactate > 4:
36.7%
30.0%
46.1%
What patients are at high risk for
global tissue hypoxia?
SvO2
4 mM/L
•
•
•
•
•
Case
78 year old female
T – 39o C
Cough
Brown sputum
Right sided chest
pain
Crit Care, 2008
12
4/11/2015
MARKER ANALYSIS
• Over 150 markers analyzed by immunoassay, including various
pro-forms, variants, and fragments.
Markers of :
Markers of :
• Pro-inflammation
(e.g., CRP, TNFα,
IL-1β, IL-8)
• Apoptosis
(e.g., caspase-3)
• Vasoregulation
(e.g., BNP, proBNP,
bigET-1, calcitonin)
• Anti-inflammation
(e.g., IL-10, IL-6,
soluble TNF
receptors)
• Organ and tissue
dysfunction
(e.g., NGAL,
myoglobin, I-FABP,
pulmonary surfactant
proteins)
• Coagulation and
fibrinolysis
(e.g., D-dimer, tissue
factor, protein C)
CREATING THE DIAGNOSTIC
MARKER CHECKLIST*
• Protein C
– Inhibits FV, FVIII, PAI-1, inhibiting
coagulation and promoting
fibrinolysis; reduces monocyte
cytokine production
• Myoglobin
– Marker of muscle
damage
– Tissue hypoxia
• CCL-19 / MIP-3b
– Chemokine expressed in lymphoid
tissues; chemoattractant for
lymphocytes, macrophage progenitor
cells and NK cells
• D-dimer
– Coagulation/fibrinolysis disorders
play a major role in organ
dysfunction during sepsis
• BNP
– Ventricular dysfunction
associated with sepsis;
prognosis and marker of
tissue hypoxia
• Myeloperoxidase
– Enzyme expressed in neutrophils;
elevated in inflammatory conditions;
exhibits microbiocidal activity
*This list includes preliminary research as of October 2005.
13
4/11/2015
THE SEPSIS MARKER PANEL MMX VALUE
EXHIBITED HIGHER ROC AUC THAN MARKERS
DESCRIBED IN THE LITERATURE
MMX and Marker ROC AUC for Low Risk vs. High Risk † on the subpopulations
of patients for which both the MMX and Marker values were determined
Enrollment Blood Draw
‡
Marker
Procalcitonin**
CRP
WBC Count
Serum Creatinine
Lactate*
Number of Patients
Low Risk Hish Risk
101
320
177
748
147
736
147
726
38
310
0.78, Lancet, 2007
ROC AUC
Marker
MMX
0.76
0.83
0.75
0.83
0.66
0.83
0.63
0.83
0.59
0.83
P-value*
0.034
0.002
<0.001
<0.001
<0.001
0.78, Int Care Med, 2002
†
Low Risk = low risk infection or non infection
High Risk = high risk infection with or without severe sepsis and/or shock at enrollment
‡ Subgroup of patients for which both the Marker and MMX were determined and compared in the paired test
* p-value for MMX Value AUC vs. Marker AUC; p-value and AUC apply to the subgroup listed under Number of Patients
** Procalcitonin was measured with the Brahms LIA assay
Stay Tuned!
•
•
•
Have blood
cultures be
drawn?
Has a lactate
been ordered.
Evaluate the
patient for
sepsis.
Antibiotics
• Have blood cultures been drawn?
• Has a lactate been ordered?
• Evaluate the patient for sepsis.
14
4/11/2015
• June 27, 2012 — The FDA has approved the first nucleic
acid test capable of quickly detecting sepsis and
identifying markers of microbial resistance.
• In less than 2.5 hours, the Gram-Positive Blood Culture
Nucleic Acid Test (BC-GP; Nanosphere Inc) detects:
– 12 gram-positive bacteria, including methicillinresistant Staphylococcus aureus, vancomycin-resistant
Enterococci, and Listeria.
• Identifies antimicrobial resistance, genes that confer
resistance to methicillin/oxacillin and vancomycin.
• 1642 patient blood samples contaminated with grampositive bacteria:
– 93% to 100% accuracy compared with blood culture
methods.
• A test for gram-negative blood cultures is currently in
development.
15
4/11/2015
The Need for Coordinated Care:
From the ED to the ICU
ED Course
•
•
•
•
•
•
•
•
•
•
54 year old male
Infected leg
B/P 107/79, HR – 76
Base deficit -10 Meq/L
BNP - 4399
Lactate 15.5, ER for 9 hours
Fluids – 4 liters, colloids
Antibiotics, Dobutamine
EGDT to ScvO2 of 78%
OR for amputation
16
4/11/2015
Where do you perform EGDT?
Emergency
Department
General
Practice Unit
Intensive
Care Unit
Hospitalist
EICU
CNP
ICU Based Strategy
17
4/11/2015
Transfer to Sepsis
Referral Centers
18
4/11/2015
You have to start somewhere and
you don’t have to be perfect!
Crit Care Med, 2007
19
4/11/2015
You need continuous quality
improvement to see the outcome
benefit
How can we over come
the constipation in
sepsis management?
20
4/11/2015
Roberta Mooney
Sepsis Coordinator at HFHS
Daily
Assessment of
all admitted
sepsis patients
Monthly
Meetings and
Reports for all
ICU’s and ED
Feed back to all
clinicians
21
4/11/2015
54.336 Billion
183% Increase
over 8 years
The Cost of Non-compliance
Noncompliance
Compliant
N
512
414
Hospital Length of Stay
20.8
15.95
Cost per admission
$191,468.3
$144,835.4
$12 Million per year
22
4/11/2015
March 6, 2013
Joint Commission
CMS
AHRQ
23
4/11/2015
2012
24
4/11/2015
Multi-center Severe Sepsis & Septic Shock Collaborative
St. Cloud Hospital
Henry Ford Hospital
Northwest Community
Detroit
Hospital
St. Joseph Mercy
Hospital
Christiana Care
Health System
California Pacific
Medical Center
Porter Memorial
Hospital
University of Kansas
Hospital
University Medical Center
at Brackenridge
Barnes Jewish
Hospital
Henry Ford Hospital
Wyandotte
25
4/11/2015
16% ARR
Kaiser, California
Ingredients of a Sepsis Program
Early
Detection
Appropriate
ICU
Disposition
Early and
Rapid
Intervention
Improved
Outcomes
ER
26
Endocrine Emergencies:
Thyroid Cases
Lori B. Sweeney, MD
VCU Health System
Famous golfers with thyroid disease
 Ben Crenshaw: 1995 Masters
Winner
 Patty Berg: Winner of the first
Women’s National Open Golf
Tournament 1946
 Pat Bradley: Top player in the
LPGA
Objectives
 Review general principles of thyroid disease
 Discuss Thyroid Emergencies
 Provide some pearls for thyroid function test interpretation
Thyroid Function Tests
Generic term for thyroid blood tests
Used to define the thyroid status of a patient
Normative ranges may be laboratory specific
Normative ranges are different for pregnancy
Normal Physiology
Auto-regulation
Changes in thyroid function related to
changes in circulating iodide concentrations:
Wolf-Chaikoff effect –
1. reversible iodide-induced inhibition of
organification (normals will “escape” from this
effect in around 10 days)
2. Inhibition of Tg proteolysis (clinically the most
significant pharmacologic effect of iodide acutely
inhibiting thyroid hormone release)
TSH
Glycoprotein consisting of alpha and beta
subunits
Binds to specific receptor on thyroid plasma
membrane
Stimulates all steps in thyroid hormone
synthesis and release.
Actions are mediated via cyclic AMP
Increases thyroid size and vascularity
Total T4 (Thyroxine)
99.97% protein bound
Half-life: approximately 1 week
Total T3 (Triiodothyronine)
99.7% of T3 is protein bound
80% comes from conversion of T4 in the
peripheral tissues
Half-life: approximately 1 day
Roughly 10 times more potent than T4
Thyroid Binding Globulin
TBG excess
TBG deficiency
 Hypothyroidism
 Liver: PBC, Acute
Hepatitis, Hepatoma
 Myeloma
 HIV
 Collagen vascular disease
 Estrogen
 Drugs: clofibrate, nicotinic
acid, Heroin
 Hyperthyroidism
 Critical Illness
 Starvation
 Liver: cirrhosis
 Protein losing enteropathy
 Drugs: glucocorticoids,
androgens
Calculating the FTI
T4 X T3 Uptake
Free Thryoxine Index
Falsely elevated in heparin therapy
Falsely decreased in phenytoin and valproic acid therapy
Free T3
Discriminates extremely well between hyperthyroid
and euthyroid patients
Discriminates poorly between hypothyroid and
euthyroid patients
Some hyperthyroid patients will have normal serum
free T4 levels but elevated serum T3 levels
(referred to as “T3 thyrotoxicosis”)
Free T4
Free T4 by equilibrium dialysis (“gold standard”)
Direct Free T4 immunoassay
Calculated FTI (obtained using the T4 with
Tuptake)
Drugs: Heparin and Furosemide increase free T4
Decreased peripheral conversion
of T4 to T3
Propranalol
PTU
Corticosteroids
Amiodarone
Non-thyroidal illness
Sodium ipodate and iopanoic acid
Thyroid hormone degradation,
clearance, GI loss
Phenobarbitol
Rifampin
Cholestyramine
Carbamazapine
TSH Elevation
Hypothyroidism
Nocturnal TSH surge
Thyroid hormone resistance
Pituitary adenoma secreting TSH
Suppressed TSH
Euthyroid Sick Syndrome
Starvation
Elderly
Hypopitutarism
Hyperthyroidism
Suppressed TSH and drugs
Glucocorticoids
Opiates
NSAIDS
Dopamine and dopaminergic agents
Somatostatin
Amphetamines
Non-thyroidal Illness
Decreased peripheral conversion of T4 to
T3
Reduction in binding to TBG (impaired
hepatic synthesis/binding inhibitors)
Serum T3 is decreased more than T4
TSH is normal to mildly decreased
Free t4 is usually normal to decreased
Reverse T3 is increased
Thyroid Emergencies
 Thyrotoxicosis----------------------Thyroid Storm
 FEVER, MENTAL STATUS CHANGE, TACHYCARDIA
 High mortality if untreated
(30%)
18 y/o
hispanic female
Postpartum x 12 weeks
Admitted for dyspnea
h/o weight loss
Sinus tach 130s
Beta-blockers started
Dyspnea significantly increased
EF 15%
PATHOGENESIS
 Underlying pathology: Graves’ disease > toxic adenoma,
toxic multinodular goiter > hypersecretory thyroid caner
 Precipitating events: infection, surgery, RAI, contrast dyes,
withdrawal of antithryoid medication, amiodarone therapy
 Less common: exogenous TH ingestion, DKA, CHF,
Toxemia of pregnancy, partuition, severe emotional stress,
PE, CVA, trauma
PATHOBIOLOGY
SARLIS NJ. REV ENDOC & METAB DISORDERS 2003
 High serum levels of circulating hormone: often not significantly
different among patients with storm and severe thyrotoxicosis
 Acute or rapid increase in TH level: especially post thyroid
surgery, administration of RAI, sudden discontinuation of lithium
or antithyroid RX
 Enhancement of cellular response to TH: infection, hypoxemia,
hypovolemia, lactic and ketoacidosi
s
)
Laboratory Findings
 Elevated total and free thyroid hormone
 Fully suppressed TSH (there is a delay however)
 Mild hyperglycemia (catecholamines)
 Hypercacemia (TH acute bone resorption,
hemoconcentration)
 Leukocytosis with left shift
 LFT abnormalities: most commonly elevated ALP
Burch and Wartofsky Scale
 Thermoregulatory dysfunction
 CNS alteration
 GI-hepatic dysfunction
 Tachycardia
 Congestive cardiac failure
 Precipitating event
 Cumulative score of 45 highly suggestive
CLINICAL EXAMINATION
 Signs of underlying pathology: significant orbitopathyGraves’, goiter (smooth vs. nodular)
 Tremor
 Hyperreflexia
 Warm, moist skin
 Widened pulse pressure
 Tachycardia-sinus tach, a fib
 CNS-can have frank psychosis
TREATMENT
 All patients with severe thyrotoxicosis should be treated in
the ICU
 Reduce TH (secretion/production): both PTU and MMI block
intrathyroidal iodine organification, PTU blocks peripheral
conversion (probably not that significant)
 PTU 200-250 mg every 6 hours
 MMI 20 mg every 4 hours
Non-oral administration of
antithyroid drugs
 Case reports of IV Methimazole (Hodak and colleagues)
 Authors prepared IV methimazole by reconstituting 500 mg
methimazole in 0.9% sodium chloride to a final solution of 10
mg/ml
 Filtered through a 0.22 mm filter and administered as “slow
IV push over 2 minutes
 Followed by a saline flush
Non-oral administration of
antithyroid drugs
 Rectal suppository
 Suppository: Zweig and colleagues prepared 14.4 g of PTU
tablets in 40 mL of light mineral oil and mixed in 36 grams of
cocoa butter solid melted in a hot water bath (maintained at
less than 60 C
 Mixture was distributed into thirty-six 1 gram suppository
mold and then frozen until solid
 Each contained 400 mg of PTU
 Administered every 6 hours
 Documented therapeutic blood levels
TREATMENT CONT.
 Inhibition of release of preformed thyroid hormone:
 Wolff-Chaikoff effect: administer “cold” stable iodine as SSKI
(8 drops every 6 hours)…..remember always at least 1 hour
after PTU or MMI
 Sodium ipodate/iopanic acid not generally used
(hyperosmolar), but they also reduce peripheral conversion
to T3, as well as T3 binding (2 gm IV, then 1 gm IV daily)
 Lithium carbonate 300mg q 6 hrs po (then aim for level of 1
mEq/L
TREATMENT CONT.
 Glucocorticoids: underlying autoimmune disease
(polyglandular type 2), increased cortisol clearance, inability
of adrenals to produce sufficient hormone in hypermetabolic
state.
 Hydrocortisone 300mg IV X 1, then 100mg q 8 hrs for a few
days, then a rapid taper (also inhibits TH release and
peripheral conversion)
 Inhibit peripheral hormone action: beta blockade with
propanalol (80-120 mg q 6 hrs po or ).5-1.0 mg IV over 10
min, followed by 1-3 mg IV over 10 min every couple of
hours. ? Peripheral conversion effect? (happens over a
week or so)
PEARLS
 Don’t be afraid to use antithryoid medications with elevated
liver enzymes (up to 4 times ULN)
 Please look for a precipitant event
 If the patient has heart failure: They will be warm!
 Antithyroid medications and vasculitis: pANCA positive, far
more common with PTU: lupus like picture with fever,
palpable purpura, splenomegaly, lymphadenopathy, serositis
of pleura and pericardium……but don’t stop meds for just
pruritic rash
 Agranulocytosis: rare treat with G-CSF
PEARLS CONT.
High output cardiomyopathy: who gets this? Generally treated with
digoxin and furosemide (often higher than usual doses),
However…..Furosemide at high doses displaces hormone from TGB
leading to increase in free hormone…..Rapid metabolism of digoxin in
the early phase…but as patient improves, dig toxicty can ensue
Acetaminophen over ASA (TH binding effects)
Cooling blankets
Fluid requirements: 3-5 liters per day are not uncommon
Hepatic Glycogen storage depletion: dextrose containing fluids, thiamine
Limited Medical Therapy Options
CHOLESTYRAMINE….I USE IT ALL THE TIME!!! 4 GRAMS
EVERY 6 HOURS…..TALK TO PHARMACIST ABOUT
TIMING OF OTHER MEDICATIONS….USUALLY AT LEAST
3 HOURS AFTER CHOLESTYRAMINE
(TH binds to the GI tract, and enterohepatic circulation is
blunted)
PLASMAPHARESIS
EMERGENT SURGERY: RAPID PREPARATION:
PROPRANALOL AT LEAST 60 MG TID
DEXAMETHASONE 2 MG IV FOUR TIMES DAILY
CHOLESTYRAMINE 4 GM ORALLY, FOUR TIMES DAILY
SSKI 2 DROPS THREE TIMES DAILY
MYXEDEMA COMA
 Severe hypothyroidism-------- Mxyedema
 Symptoms along a continuum
 Often misdiagnosed in septic patient (altered sensorium,
hypotension…..sometimes hypothermia)
 Often insidious onset…..elderly patient off LT4 therapy
 Often precipitating factor (same as thyrotoxicosis)
MULTIORGAN DISORDER
 Thyroid hormone receptor is present on virtually every cell
type, is even a neurotransmitter
 Cardiovascular system: the hypothyroid heart
(cardiomegally, decreased contractility, bradycardia),
pericardial effusion (SIADH/volume overload), diastolic
hypertension
 Renal system: hyponatremia, decreased GFR, resulting in
decreased excretion of water load, and SIADH (urine will be
inappropriately concentrated)
Multi-organ disorder cont.
 Respiratory system: Alveolar hypoventilation, hypercapnea,
respiratory muscle myopathy
 Can be complicated by OSA (often present with
hypothyoidism…..hypogonadism associated with OSA as
well), macroglossia
 GI system: decreased motility, bowel wall edema, parlytic
ileus/megacolon
 Neurological system: can have frank psychosis and
generalized seizure
LABORATORY FINDINGS
 Low free and total TH, markedly elevated TSH (remember
delay)
 Hyponatremia
 Hypoglycemia
 Marked CPK elevation (increased skeletal muscle cell
memebrane permeability)
 Low WBC count
 Macrocytic anemia (B 12 malabsorption)
 Other studies: LP: increased ICP and CSF protein, EEG
alpha wave activity (hyponatremia, hypoglycemia)
TREATMENT
 Why don’t we treat in all suspicious cases…….myocardial
ischemia
 300-600 µg IV (4 mcg/kg lean body weight), then 50-100 µg
daily (supraphysiologic TH for 24 hrs-monitoring crucial),
continue until patient can be transitioned to PO regimen
(usually 125-150 µg daily)
PEARLS
Low normal TSH, with frankly low free T4: Central hypothyroidism (rule
out panhypopit), or non-thyroidal illness
Dopamine has most data for hypotension
Get both baseline cortisol and if possible perform ACTH stim
Patient with severe hyponatremia and volume overload: monitory
pulmonary capillary wedge pressure and administer hypertonic saline
but don’t correct sodium more than 10mEq/L
 What about T3? Controversial….limited outcome data..
Suggested doses range from 2.5 to 25 mcg IV every two hours for up to
48 hours…..not in the patient with ASCAD…simultaenous with
T4…………if I use it….upper range is 10 mcg q 12 hours …or add after
48 hours if no improvement on LT4 alone
Case 1
62 female vasculopath with history of atrial
fibrillation, ASCAD, PVD, Type II DM admitted
to ED for DOE progressive over several days
Approximately 6 months ago she was admitted
for rapid AFIB and was treated with amiodarone
Case 1
Lab
measure
Total T4
12.0 µg/dl (4.6-12)
Free T4
3.5 ng/dl (0.7-1.9)
Total T3
220 ng/dl (80-240)
TSH
<0.01 (0.5-5)
a-TPOab
negative
TSIIab
negative
Case 1
 How do you explain the tfts?
Lab
measure
Total T4
12.0 µg/dl
Free T4
2.5 ng/dl
Total T3
220 ng/dl
TSH
<0.01
a-TPOab
negative
TSIIab/TRAB negative
Inappropriately normal
Euthyroid sick
component
Inappropriately normal
Diminished type 1-5
deiodinase
Underlying autoimmunity
Likely Type
2 AIT
Case 2
18 y/o female with history of eating disorder is
admitted for sinus tachycardia, fever
She has 10kg weight loss, insomnia, shortness
of breath, irregular menses
Case 2
LAB
MEASURE
Free T4
4.0 (0.7-1.9)
Total T3
260 (80-240)
TSH
<0.10 (0.5-5.0)
TGB
0.5
TPO-ab
negative
Case 3
44 y/o male admitted for bradycardia,
hypotension, altered mental status,
hyponatremia and mild hypothermia
PMH also significant for weight loss,
diminished libido, peripheral visual field deficit
Case 3
Lab
measure
Total T4
2.8 µg/dl (4.6-12)
Free T4
0.4 mg/dl (0.7-1.9)
Total T3
83 ng/dl (80-240)
TSH
0.30 µU/ml (0.5-5)
a-TPOab
negative
TSII0ab
negative
Why is this
normal?
Case 3
What is the diagnosis?
What if the patient presented with severe
thunderclap headache?
What therapy would you initiate?
Any other tests?
Case 3
Supportive therapy is initiated and
supplemental thyroid hormone is administered
Hypotension worsens?
What test should have been done?
Questions?
Critical Illness
Polyneuromyopathy
H. Erhan Dincer, MD
Associate Professor of Medicine
Director, Interventional Pulmonology & Bronchoscopy
Pulmonary, Critical Care & Sleep Medicine
University of Minnesota
Disclosure
Consultant
Spiration/Olympus
Holaira
Boston Scientific
Outline
Critical illness polyneuropathy and myopathy
 Definition
 CIP and CIM





Pathophysiology
Risk factors
Diagnosis
Prevention and Treatment
Outcome
Definition/Terminology
Variation in terminology and nosology
 “Rapid loss of flesh” in prolonged sepsis by Osler in
1892
 “Severe motor dysfunction” in septic patients during
convalescence in the 1980s
 Neuromuscular diseases in the ICU last 25 years
 Critical illness polyneuropathy (CIP), critical illness
myopathy (CIM)
 CIPNM, ICU-acquired weakness (ICU-AW)
CIP
 Distal axonal sensory-motor
polyneuropathy
 Limbs and respiratory muscles,
SPARES facial muscles
 Symmetrical
 Lower extremity>upper extremity,
distal>proximal
CIP
Clinical features
 Difficulty weaning from MV
 Independent risk factor for failed weaning and prolonged MV
 Only facial grimacing on painful nail bed stimulus
 DTR might be preserved or reduced
 If alert;
 Distal loss of pain/temp/vibration
 Medical Research Council (MRC) scale or handgrip
dynamometry for limb and MIP/MEP, VC for respiratory muscle
strength
CIP
 MRC combined into a sum
score
 A score < 48 defines ICUacquired weakness
 Prolongation of MV, ICU stay,
increased mortality, reduced
QOL in ICU survivors
Fletcher et al, CCM 2003;31:1012
CIP
Electrophysiological features
 Amplitude reduction or missing
compound motor action potentials
(CMAP) and sensorial neural action
potentials (SNAP)
 Reduction in nerve conduction
velocity (NCV)
 Muscle EMG; fibrillation potentials
with sharp waves
CIP
Histologic features
 Nerve biopsy
 Axonal degeneration with
decreased density of myelinated
fibers, rarely indicated
 Muscle biopsy
 Acute denervation of muscle
atrophy of both type 1 and 2 fibers
Sural biopsy
CIP diagnostic criteria
 Multiorgan dysfunction or failure
 Limb weakness or difficulty weaning from MV after nonneuromuscular causes excluded (heart or lung)
 Electrophysiological evidence of axonal motor or
sensory polyneuropathy
 Absence of a decremental response on repetitive nerve
stimulation (e.g. motor neuron disease, MG)
CIM
Clinical features
 Primary myopathy, not due to denervation
 Difficulty weaning from MV
 Flaccid limbs, some reduction in DTRs
 Normal sensation, if testable
CIM
Electrophysiological features
 Amplitude reduction and duration increase in CMAP, normal
SNAP and abnormal EMG
CMAP in septic patient now
and 3 weeks alter
Needle EMG of tib ant; low amplitude, polyphasic motor unit
potentials
CIM
Histologic features
 Muscle biopsy
 Selective loss of thick
filaments (myosin) and
varying degrees of necrosis
CIM diagnostic criteria
 Multiorgan dysfunction or failure
 Limb weakness, difficulty weaning from MV after non-neurologic
causes (heart, lung) excluded
 CMAP amplitude < 80% of the lower limit of normal in ≥ 2
nerves
 SNAP amplitude > 80% of the normal limit of normal
 Needle EMG
 Low amplitude, polyphasic potentials,  CMAP duration
 Absence of decremental response to repetitive stimulation
 Primary myopathy on muscle biopsy (myosin loss, necrosis)
CIM
Bedside ultrasound of the muscle
 28 sepsis/septic shock
 First pilot study
 26/28 + CIPNM by EP & exam
 US echogenicity grading
 Muscle edema in early stage
(Day 4)
 Fibrosis and fatty degeneration
in late stage (Day 14)
 Edema  atrophic & fibrous
changes by MRI (1 patient)
Grimm et al, Crit Care 2013;17:R227
Combined CIP + CIM
 Can occur
 Mild or severe
 Mild;
 Some features of electrophysiological changes of CIP
and CIM, normal biopsy, good recovery
 Severe;
 Most features of electrophysiological changes of CIP and
CIM, abnormal muscle biopsy, complete recovery may
not happen and prolonged need of rehab
Pathophysiology
Incidence of CIP & CIM
 Patients on MV for 4-7 days or with high risk of
developing MOFS;
 25%-30% on clinical assessment
 30%-60% on electrophysiological assessment
 Patients with ARDS
 24%-77% (> 1 week in the ICU)
 55%-80% (MOFS and SIRS)
 100% (severe sepsis or septic shock)
De Jonghe et al. Intens Care Med, 2004;30:1117
Risk factors of CIP & CIM
 Sepsis
 SIRS
 MOFS
 Immobility
 Mixed results;




Aminoglycosides
Neuromuscular agents
Corticosteroids
Hyperglycemia
Risk factors of CIP & CIM
Independent risk factors
 Severity of illness
 Duration of MOFS (≥2) with or without SIRS
 Duration of vasopressor or catecholamine support
 Duration of ICU stay
 Hyperglycemia
 Female sex
 Renal failure or RRT
 Hyperosmolarity
 Low serum albumin, parenteral nutrition
Risk factors of CIP & CIM
SIRS, sepsis, MOFS
 Prospective studies
 Electrophysiology, APACHE III scores and the
presence of SIRS were independently associated with
CIP & CIM
 Mechanism: unclear, may be a “local phenomena”
 Ischemia or injury of nerve and muscle via mediators of
local inflammation (cytokines), increased vascular
permeability (expression of adhesion molecules on
vascular endothelium)
 IL-6 and TNF are NOT increased
Risk factors of CIP & CIM
Corticosteroids
 Animal models, selective muscle atrophy
 Combination of denervation injury + steroids cause
muscle changes identical to CIM
 Mechanism:
 May activate muscle proteolysis and deplete muscle
proteins
 Mixed results on prospective studies
Corticosteroid-induced Myopathy
 Pre-existent condition
 Excess of external or internal (adrenal tumors) steroids
 Upper/lower limbs (proximal) and neck flexors,
 Weakness, difficulty weaning from MV
 More often with fluorinated steroids (dexamethasone,
triamcinolone) than nonfluorinated (prednisone,
hydrocortisone), prednisone 40-60mg/d for weeksmonths
 Acute (high dose, associated with rhabdo) or chronic
Risk factors of CIP & CIM
Neuromuscular blocking agents
 Mixed results
 Prolonged use and accumulation in the setting of
renal/liver failure
Risk factors of CIP & CIM
Immobility
 Contributing in presence of other risk factors
 Prolonged sedation, bed rest are independent risk factors
for ICU weakness when adjusted for duration of MOFS
 Diaphragm atrophy when MV fully controlled
 Repeated daily passive mobilization prevents muscle
atrophy in mechanically ventilated patients
Risk factors of CIP & CIM
Glycemic control
 50% reduction in evolution of CIP in surgical patients
who treated with tight glycemic control when compared
to conventional control
Van den Berghe et al. CCM 2003;31:359
 Mixed results
Diagnostic algorithm
Differential Diagnosis
 Myopathy due to electrolyte abnormalities
 Hypokalemia, hypophosphatemia, hypocalcemia
 Acute or chronic effect of medications
 Acute; NMBA, steroids
 Chronic; chemotherapy, antiretroviral, statins
 Propofol related infusion syndrome
 Guillain-Barre syndrome
 Post surgical axonal neuropathies
Differential Diagnosis
Propofol-related Infusion Syndrome
 Severe metabolic acidosis, cardiac failure,
rhabdomyolysis, renal failure, hypertriglyceridemia
 Propofol use > 48 hours, > 5mg/kg/h
 1% incidence, more common in head trauma and acute
inflammatory syndromes
 Rhabdomyolysis (normal muscle biopsy)  acute
necrotizing myopathy
 Treatment; stop propofol, supportive
Differential Diagnosis
Guillain-Barre syndrome
 Autoimmune polyneuropathy
 C. jejuni infection with diarrhea often precedes the
progressive muscle weakness including respiratory
failure
 Facial muscles are usually involved (not in CIP)
 Clinical and electrophysiological studies can not
differentiate GB from CIP
 Serial electrophysiological studies needed
 Treatment: IVIG, plasmapheresis
Differential Diagnosis
Post surgical inflammatory axonal neuropathies
 In the absence of nerve compression, contusion,
stretching or transection
 Polyneuropathy away from the surgical site
 Focal, multifocal or diffuse forms
 Focally increased T2 signal on MRI, nerve biopsy for
definitive diagnosis
 Treatment: IV methylprednisone, IVIG
Staff et al. Brain, 2010;133:2866
Prevention & Treatment
Risk factor modifications
 Avoid corticosteroids and NMBA
 Tight insulin control (surgical patients)
 Sedation sparing protocols
 Early limb mobilization
 Electrolyte management (magnesium, phosphorus)
 Optimal nutrition
 Ventilator weaning protocols
Prevention & Treatment
Avoid corticosteroids
 Benefit of corticosteroids in sepsis, ARDS or
pneumonia obscure
 Before fibrotic phase of ARDS, severe sepsis (BP<90
mmHg in spite of fluids and pressors)
Prevention & Treatment
Avoid NMBA
 Depolarizing; succinylcholine (hyperkalemia, malignant
hyperthermia)
 Non-depolarizing;
 Benzylisoquinolium (cisatracurium, atracurium)
 Aminosteoid (Roc, vec, pancuronium)
 Use in ICU; early ARDS, improve oxygenation,
decrease inflammatory response, improve mortality
Papazian et al, NEJM 2010;363:1107
 Aminosteroids more strongly implicated in CIP/CIM
Prevention & Treatment
Tight insulin control
 BG 80-110 mg/dl showed fewer cases of CIP by
electrophysiological studies after day 7 (28% vs 52%,
p< 0.001) in surgical and medical patients
Van den Berghe, et al. NEJM2001;345:1359
Hermans, et al. AJRCCM 2007;175:480
 Tight insulin control is associated with increased
mortality in the ICU
Finfer, at al. NEJM 2009;360:1283
 Target BG 140-180mg/dl
Prevention & Treatment
Sedation sparing protocols
Under Sedation
-
Self extubation
Removal of lines
Increased systemic/myocardial O2
consumption
Failure to participate therapeutic
interventions
Over Sedation
-
Increased ICU/hospital stay
Increased time on ventilator
Increased delirium
Increased VAP
Long term psychological problems
Difficult neurologic assessment
 Sedation scales (RASS), protocols (nurse directed,
patient directed), daily sedation interruption, new
generation medications (dexamedetomidine)
Prevention & Treatment
Early mobilization
 Changing paradigm
Prevention & Treatment
Prevention & Treatment
Prevention & Treatment
Early mobility (Prospective cohort study of 165 patients)
 All outcomes adjusted for severity of illness
 All patients had daily spontaneous awakening and breathing trials
Morris et al, CCM 2008;36:238
Prevention & Treatment
Early mobility
 104 sedated, vented patients, prospective randomized
 Both groups had sedation protocol and daily SAT/SBT
Schweickert et al, Lancet, 2009;373:1874
Prevention & Treatment
Feasibility of PT/OT beginning from initiation of MV
49 vented patients received PT/OT a median of 1.5 days
after intubation
 Edge of bed (69%), bed to chair (33%), stood (33%) and
ambulated (15-20 ft) (15%) of patients
 16% adverse effects (tachycardia, tachypnea)
 4% early interruption due to agitation and patientventilator asynchrony
Pohlman et al, CCM 2010;38:2089
Prevention & Treatment
Implementing the ABCDE bundle in the ICU
ABC
D
Awakening &
Breathing Trial
Coordination
E
Delirium
Assessment &
Management
Early Exercise &
Progressive
Mobility
Balas et al, CCN 2012;32:35
Prevention & Treatment
Electrical Muscle Stimulation
 140 critically ill (APACHE II>13), a randomized parallel
intervention trial (Daily EMS to lower extremity only)
 EMS group (n=68) daily EMS
 Control group (n=72)
Routsi et al, Crit Care 2010;14:R74
Prevention & Treatment
Electrical Muscle Stimulation
 140 critically ill (APACHE II>13), a randomized parallel
intervention trial (Daily EMS to lower extremity only)
 EMS group (n=68) daily EMS
 Control group (n=72)
P=0.01
P=0.11
Routsi et al, Crit Care 2010;14:R74
Prevention & Treatment
IgM-enriched IVIG
 38 critically ill patients randomized (MOFS and SIRS/sepsis)
 CIPNM score based on electrophysiology and muscle biopsy
IVIG did not mitigate CIP or CIM
Brunner et al, Crit Care 2013;17:R213
ARDS Outcome
 Canadian cohort study of 109 ARDS survivors for 1 year
 Median age; 45, median APACHE II; 23, median ICU LOS;25 d
ARDS Outcome
At 1 year
 49% back to work
 ALL described poor function due to weakness, fatigue
 PFT improved except for DLCO remained low, 6 MWT limited
due to neuromuscular complaints
Outcome
Survivors of critical illness
 Neuromuscular recovery may take years
Long term outcome in patients with CIP and CIM
 36 study, 263 patients, follow up 3 to 6 months
 Complete functional recovery 68%
 Severe disability (quadriparesis or plegia) 28%
Latronico et al, Curr Opin Crit Care, 2005:11:126
CIP/CIM Outcome
Critical illness myopathy and/or neuropathy (CRIMYNE)
 1 year prospective cohort study of 92 patients
 28 diagnosed CIP and/or CIM while in the ICU
 18 had persistent CIP and/or CIM at discharge
Guarneri et al, J Neurol Neurosurg Psych, 2008;79:838
Take Home Messages








CIP and CIM are different entities but may occur together
Both presents as difficulty weaning from MV—too late!!
CIP (motor-sensory); limbs, resp muscles, not face
CIM; flaccid limbs, normal sensation
Diagnosis: Neurol exam, EP studies, muscle biopsy
Avoid risks as much as possible (drugs)
Implementation of sedation, weaning protocols
Early diagnosis and intervention (mobilization)
Capnography: Basic Concepts And
Clinical Utility
53nd Annual Weil/UC San Diego Symposium on
Critical Care & Emergency Medicine
(April 11, 2015)
Raúl J. Gazmuri MD, PhD, FCCM
Resuscitation Institute
at Rosalind Franklin University
and
Captain James A. Lovell Federal
Health Care Center
(Section of Critical Care Medicine)
Conflicts
• Funding for research on various aspects of
resuscitation from cardiac arrest and
hemorrhagic shock and role of mitochondria
(DoD, VA Merit Review, Zoll, Baxter, Friends
Medical Research Institute, DePaul-RFU, and
ALGH)
• None related to the current presentation
CAPNOGRAPHY
A Few Basic Concepts…
CAPNOGRAPHY
 Capnography is a non-invasive technique
whereby the change in partial pressure of
carbon dioxide (PCO2) in the gases
entering and leaving the lungs is
graphically displayed and analyzed
quantitatively and qualitatively.
 Capnography can be measured in patients
intubated for mechanical ventilation or in
non-intubated patients using mainstream
or sidestream technology.
CAPNOGRAPHY
 CO2 in the respiratory gases can be
measured by:
 Mass Spectrometry: For research purposes;
expensive and not clinically practical or necessary
 Colorimetric: Chemical reaction; semi-quantitative
and does not provide good temporal resolution
and waveform analysis
 Infrared absorption spectroscopy: Preferred
method; quantitative with waveform capabilities,
widely available in stand-alone devices and
incorporated to bedside monitors, defibrillators,
pumps, etc.
BASIC INFRARED TECHNOLOGY
Sample chamber with
CO2 absorbing light
Infrared light
detection
Infrared light
emitter
Filter
Detector
CAPNOGRAPHY
Mainstream
Technique
CAPNOGRAPHY
Sidestream
Technique
To capnograph
(~150 ml/min)
Patient
Ventilator Adaptor
tubing
 End-inspiration and beginning of exhalation
 Early exhalation
 Exhalation and end-tidal PCO2
 Inspiration


0


End-Tidal PCO2
d
40
c
a
b
e
Baseline (a-b)
Rapid sharp rise (b-c)
Alveolar plateau (c-d)
Rapid,
sharp descend (d-e)
CAPNOGRAPHY
Production
VCO2
Ventilation
Transport
DCO2
Vd/Vt
CAPNOGRAPHY
Accordingly, end-tidal PCO2 is a
function of:
 VCO2
(CO2 production)
 DCO2
(CO2 transport)
 Vd/Vt
 VE
(dead space ventilation)
(minute ventilation)
CAPNOGRAPHY
VCO2
DCO2
Vd/Vt
VE
PETCO2
VCO2 (CO2 production)
 Increased

metabolic activity
Fever, malignant hyperthermia, shivering,
exercise, hyperthyroidism, seizure
activity, pain, stress
 Decreased

metabolic activity
Hypothermia, hypothyroidism, sedation,
muscle paralysis
CAPNOGRAPHY
VCO2
DCO2
Vd/Vt
VE
PETCO2
DCO2 (CO2 transport)
 Decreased

 Diversion

blood flow
Cardiac arrest, CPR, severe shock
(hypovolemic, cardiogenic, obstructive)
of blood flow
Extracorporeal circulation
CAPNOGRAPHY
VCO2
DCO2
Vd/Vt
VE
PETCO2
Vd/Vt (dead space ventilation)
 Increased

dead space ventilation
Pulmonary embolism (clots, air, tumor,
amniotic fluid), increased zone A, decreased
tidal volume
CAPNOGRAPHY
VCO2
DCO2
Vd/Vt
VE
PETCO2
VE (minute ventilation)
 Increased

(hyperventilation)
Mechanical ventilation, anxiety, fever, pain,
metabolic acidosis
 Decreased

(hypoventilation)
Mechanical ventilation, respiratory muscle
fatigue, neuromuscular disease, drug
overdose, metabolic alkalosis
CAPNOGRAPHY
Some applications…
CAPNOGRAPHY
Confirmation tracheal
intubation
Highlights of 2010 Guidelines
Waveform Capnography
Verification endotracheal tube placement
(Class I, LOE A)
CAPNOGRAPHY
Monitoring ventilation
Non-invasive monitoring of CO2 is standard of care by the ASA
since July 2011 for monitoring moderate and deep sedation
Hyperventilation
Hypoventilation
J Anesth Clin Res. Mar 18, 2013; 4(3): 295
Non-invasive monitoring of CO2 is standard of care by the
ASA since July 2011 for monitoring moderate and deep
sedation
Pulse oximetry in patients
receiving room air or
supplemental oxygen at 2
L/min during an episode of
hypoventilation.
J Anesth Clin Res. Mar 18,
2013; 4(3): 295
CAPNOGRAPHY
Diagnosing diabetic
ketoacidosis
Predictive Value of Capnography for Suspected Diabetic
Ketoacidosis in the Emergency Department
West J Emerg Med. Nov 2013; 14(6): 590–594.
Predictive Value of Capnography for Suspected Diabetic
Ketoacidosis in the Emergency Department
West J Emerg Med. Nov 2013; 14(6): 590–594.
Sixty-two of 181 patients
had DKA, with significant
differences in pH,
bicarbonate, PaCO2, and
PETCO2 (p≤0.001)
PETCO2 > 24.5 mmHg could
rule out DKA with a
sensitivity and specificity
of 0.90
PETCO2 < 24.5 mmHg could
not differentiate between
DKA and other disease
entities
CAPNOGRAPHY
Pulmonary embolism
CAPNOMETRY IN SUSPECTED PULMONARY EMBOLISM
WITH POSITIVE D-DIMER IN THE FIELD
Crit Care. 2009; 13(6): R196
Patients total
131
No 31
PETCO2 > 28 mmHg and
low clinical probability is a
potentially safe method for
excluding PE in patients
with suspected PE and
positive D-dimer test
Inclusion criteria
Di-dimer +
Yes 100
Clinical probability of PE (Wells criteria)
Unlikely 55
PETCO2
nasal
> 28 mmHg < 28 mmHg
35
20
PE 0
PE 14
Likely 45
> 28 mmHg < 28 mmHg
17
28
PE 3
The combination of
PETCO2 < 28 mmHg and
high clinical probability is
a potentially safe method
for confirmation of PE in
patients with suspected
PE and positive D-dimer
PE 24
CAPNOGRAPHY
• 51 year old man had internal fixation of fractured
olecranon
• On day 2, he abruptly developed intense dyspnea followed
by apnea and pulseless
• CPR reestablished ROSC after 24 min
• Chest x-ray unremarkable
• EKG RBBB
• Arterial pCO2 was 50 mmHg and the PETCO2 was 21 mm Hg
• Bedside transthoracic echocardiogram showed RV dilation
• Tenecteplase was given and within 75 minutes the RBBB
normalized
• A CT angio on day 4 confirmed small filling defect in the a
proximal right pulmonary artery branch
CAPNOGRAPHY
• 50 year old man admitted for the diagnosis of PE
complained of chest pain
• Chest pain intensified developing signs of reduced
peripheral perfusion with altered mentation and
intensification of chest pain
• Jugular vein distension
• Patient transferred to ICU for intubation and
hemodynamic monitoring/management
• Arterial pCO2 was same as PETCO2
• Bedside transthoracic echocardiogram showed 4chamber dilation
• Patient referred for coronary angiography and CABG
CAPNOGRAPHY
Monitoring CPR efficacy
CPR
• Chest compression
•Blood flow generation
• Ventilation
•Oxygenation
•Removal of CO2 (?)
Coronary Perfusion
Ao-RA pressure between
compressions
Pressure
Aorta==Flow
COx Resistance
x PVR
CPR
Vasopressors
CHEST COMPRESSION
+
+
+
+
+
+
+
+
Forward Blood Flow
120
Venous Return
Cardiac Output, ml/min
100
(n = 7)
80
60
40
20
0
6
Myocardial blood flow, ml/min
5
4
3
2
1
0
BL
CC
PR 15 min
PR 60 min
Kolarova at al AJP 2005; 288:H2904
Depth of Compression Determines
Forward Blood Flow
Normalized CO
Babbs et al. Ann Emerg Med 1983;12:527
1.5
1.0
0.5
0
0
4
2
Depth, cm
6
ETCO2 vs CARDIAC INDEX DURING CHEST COMPRESSION IN PIGS
(24 observations in 7 animals)
5
ETCO2 = 0.038 CI – 0.44
r = 0.91 p < 0.001
ETCO2, %
4
3
2
1
0
0
20
40
60
80
CARDIAC INDEX, ml/min/kg
100
End Tidal PCO2 During CPR
Sanders AB et al. JAMA 1989;262:1347-52
p < 0.001
25
mmHg
20
15
10
5
Resuscitated
0
Non Resuscitated
PETCO2: A Clue on the Mechanism of
Cardiac Arrest
Difference in end-tidal CO2 between
asphyxia cardiac arrest and ventricular
fibrillation/pulseless ventricular
tachycardia cardiac arrest in the
prehospital setting
Štefek Grmec, Katja Lah, and Ksenija TušekBunc
Center of Emergency Medicine, Prehospital Unit
Maribor, Maribor, Slovenia
Crit Care 2003; 7: R139–R144
PETCO2: A Clue on the Mechanism of
Cardiac Arrest
PETCO2 (mmHg)
Asphyxia
(n = 44)
VF/VT
(n = 141)
Immediate after ET
66 ± 17
17 ± 9
At 1 min of CPR
29 ± 5
24 ± 5
ROSC (yes)
36 ± 9
30 ± 8
ROSC (no)
19 ± 9
14 ± 5
Grmec S et al. Crit Care 2003;7:R139
PORCINE MODEL OF VF AND CLOSEDCHEST RESUSCITATION
LUCAS Device
CAROTID
BLOOD FLOW
AIRWAY PRESSURE
AND FLOW
ECG
PETCO2
VENTILATOR
(PB 840)
PACING
ELECTRODE
(induce VF)
5
0
-10
*
*
AORTA
RIGHT ATRIUM
(microtip P-T) (microtip P-T)
*
Airway flow and airway pressure
during chest compression measured
immediately before delivery of a
positive pressure breath. Data were
averaged from measurements
obtained at minutes 2, 4, 6, and 8 of
chest compression and presented as
mean ± SEM.
Airway Flow
(L/min)
-20
The top graph depicts mean airway
flow denoting gas movement from the
respirator to the lungs (positive values)
and from the lungs to the respirator
(negative values). *p < 0.05 vs 33/18
by Holm-Sidak method using all
pairwise comparisons after
establishing overall significance by
one-way ANOVA (p = 0.028).
-30
16
12
Airway Pressure (mmHg)
The bottom graph depicts the airway
pressure measured during chest
compression (higher values) and
during chest decompression (lower
values). *p < 0.05 vs 33/18 by StudentNewman-Keuls method using all
pairwise comparisons after
establishing overall significance by
one-way Kruskal-Wallis ANOVA for
pressures during chest compression (p
= 0.023) and for pressures during
chest decompression (p = 0.013).
8
4
*
10/6
*
*
-4
*
*
*
0
10/18
33/6
33/18
RR (min-1)/TV (ml/kg)
60
Respiratory Rate (10-bpm)
Tidal volume (6-ml/kg)
Tidal volume (18-ml/kg)
50
PETCO2 (mmHg)
RR = Respiratory rate; TV = Tidal
volume.
Respiratory Rate (33-bpm)
Tidal volume (6-ml/kg)
Tidal volume (18-ml/kg)
40
30
20
10
PETCO2 = 10.3 + 61.2/minute-volume; R2 0.85, p< 0.0001
0
0
400
8000 12000 16000
Minute-Volume (ml/min)
20000
CAPNOGRAPHY
Return of native circulation
OPEN- CHEST PIG MODEL OF VF
LAD Flow
meter
100% O2
Flow meter
PET CO2
VENT
100% O2
Punch
biopsies
Lactate (Enzyme)
Liquid HEM (HPLC)
Nitrogen Ions (AAS)
Protein (Western blot)
ECG
LV
PA
High-fidelity
Microtip pressure
transducer
LV
Vent
EchoDoppler
AORTA
CAPNOGRAPHY
Changes in waveform
morphology
Normal morphology
“Shark fin” morphology
in patients with airway
disease (asthma, COPD)
Apnea, disconnection
from mechanical
ventilation
Rebreathing, moisture
and/or secretion in
adaptor
J Anesth Clin Res. Mar 18, 2013; 4(3): 295
“Shark fin” pattern typical
of patients with airway
disease (e.g., COPD).
Slow expiratory flow
typically interrupted by
inspiration (i.e., leading to
air trapping) with occasional
long expirations allowing
complete exhalation.
Forced Expiratory Capnography and Chronic Obstructive
Pulmonary Disease (COPD)
J Breath Res. Mar 2013; 7(1): 017108.
Natural log transformed slopes
of plateau phase of the exhaled
CO2 during forced exhalation for
1- 6 seconds (p=0.008).
Natural log transformed slopes of
plateau phase of the exhaled CO2
during forced exhalation (1-6 s) for
the COPD subjects vs percent of
voxels below -950 HU by HRCT.
Cardiac Oscillations
EKG (V1)
50-
Capnography
250SpO2
Respirations
1s
Ventilation
Production
VCO2
Transport
DCO2
Vd/Vt
a
b
c
d
e
f
Update on Acute Kidney Injury
Kevin K. Chung, MD, FCCM, FACP
U.S. Army Institute of Surgical Research
The opinions or assertions contained herein are the
private views of the author and are not to be construed
as official or as reflecting the views of the Department
of the Army or the Department of Defense.
Grant support from the American Burn Association and
the Air Force.
U.S. Army Institute of Surgical Research
Overview
• Diagnosis
• Prevention/treatment
• Contrast induced nephropathy
• CRRT vs IHD
• Crystalloid of choice
U.S. Army Institute of Surgical Research
True or False?
As little as a 0.3 increase in SCr
results in the diagnosis of AKI.
U.S. Army Institute of Surgical Research
Acute Dialysis Quality Initiative
2nd International Consensus Conference
U.S. Army Institute of Surgical Research
AKIN Classification
Mehta et al. Crit Care. 2007 Mar 1;11(2):R31.
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
NephroCheck®
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
Question
In a patient at risk for post-ischemic ATN,
which of the following preventive
therapies have been shown improve
mortality in prospective RCTs?
A.
B.
C.
D.
Dopamine
Fenoldopam
Atrial Naturetic Peptide
None of the above
U.S. Army Institute of Surgical Research
Ischemic ATN
• Two major mechanisms
– Occlusion of tubular lumen by cellular debris
– Loss of intact or necrotic tubular cells
• Causing ‘backleak’
U.S. Army Institute of Surgical Research
Potential Preventive
Therapies
U.S. Army Institute of Surgical Research
Dopamine in ATN
• Bellomo et al. (Lancet Dec 2000;35:2139-43)
– Randomized, double blind, placebo controlled,
multi-center
– N=328, ICU patients
– Low dose dopamine (2 mcg/kg/min) vs
placebo
– No difference in selected outcomes
• Dialysis, ICU/hospital stay, mortality
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
Atrial Natiuretic Peptide
• Natriuretic and diuretic hormone
• Peripheral vasodilator
– Lowers systemic blood pressure (BP)
• Causes both afferent dilatation and
efferent constriction
• Improves renal blood flow
• Beneficial in preventing contrast induced
ARF and ATN in animal models
U.S. Army Institute of Surgical Research
Atrial Natiuretic Peptide
• Allgren et al. (N Engl J Med Mar 1997;336(2):828-34)
– Randomized, double-blind, placebo controlled,
multi-center
– N=504, ICU patients with ATN
– Anaritide vs placebo
– Overall, no difference in dialysis free survival
in 21 days
• In subgroup of 120 pts with oliguria, better outcome in
anaritide group
• In subgroups of 378 pts with non-oliguria, worse
outcome in anaritide group
U.S. Army Institute of Surgical Research
Atrial Natriuretic Peptide in
oliguric acute renal failure
• Lewis et al. (Am J Kidney Dis. 2001 feb;37(2):454-5.)
– Randomized, double-blind, placebo controlled,
multicenter
– n=222 patients with oliguric renal failure
– Atrial natriuretic peptide vs placebo
– No difference in dialysis free survival at 21
days
• 21% vs 15% (p=0.22)
U.S. Army Institute of Surgical Research
Fenoldopam
• A selective postsynaptic dopamine agonist
(D1-receptors)
– Exerts hypotensive effects by decreasing
peripheral vasculature resistance with
increased renal blood flow, diuresis, and
natriuresis
– 6 times as potent as dopamine in producing
renal vasodilitation
U.S. Army Institute of Surgical Research
Fenoldopam
• Morelli et al. (CCM. 2005 Nov)
– Prospective, double blind RCT
– N = 300 septic patients with normal serum
creatinine
– Fenoldopam 0.09 mcg/kg/min vs placebo
continuous drip
– Incidence of ARF lower in fenoldopam
group
• 29 vs 51 patients (p = 0.006)
• No mortality benefit
U.S. Army Institute of Surgical Research
Meta-analysis
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
Need for RRT
NNT = 25
U.S. Army Institute of Surgical Research
Death
NNT = 25
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
U.S. Army Institute of Surgical Research
Question
In a patient at risk for post-ischemic ATN,
which of the following preventive
therapies have been shown improve
mortality in prospective RCTs?
A.
B.
C.
D.
Dopamine
Fenoldopam
Atrial Naturetic Peptide
None of the above
U.S. Army Institute of Surgical Research
Question
47 y/o man with a 20 yr hx of DM is admitted
with an STEMI. His Cr is 2.8. An emergent
cath is planned. All of the following has
been shown to decrease the risk of contrast
induced nephrotoxicity EXCEPT.
A.
B.
C.
D.
E.
F.
G.
Nonionic iso-osmolar contrast
Fenoldopam
Oral Mucomyst
IV Mucomyst
Vitamin C
Prophylactic hemofiltration
Sodium Bicarbonate
U.S. Army Institute of Surgical Research
Contrast induced nephropathy
• Reported incidence widely variable
–
–
–
–
Normal renal function (<1%)
Mild-mod renal insuff alone (4-11%)
CRI + DM (9-38%)
Baseline Cr 4-5 mg/dL (50%)
• Elevated Cr within 24 hours
• FENa typically very low
• Prevention is key
– Avoidance in high risk patients
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Contrast induced nephropathy
• Mechanism
– Vasoactive effects
• Vasodilation => Intense Vasoconstriction
– Patients with impaired compensatory mechanisms
» CRI, DM, CHF, cirrhosis
– Direct toxic effects
• Tubular injury in association with oxygen free radicals
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Risk Factors
•
•
•
•
•
•
Preexisting renal dysfunction
Diabetic nephropathy
Severe CHF
Volume depletion
Elderly patient
High total dose of contrast agent
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Types of contrast
• Ionic hyper-osmolar agent
– 1500-1800 mosmol/kg
• Nonionic low-osmolar agent
– 600-850 mosmol/kg
• Nonionic iso-osmolar agent
– 290 mosmol/kg
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Iso-osmolar BETTER
• Aspelin et al (N Engl J Med 2003 Feb 6;348(6):491-9)
– Randomized, double-blind, prospective, multi-center
– N=129, high-risk patients (DM with CRI) undergoing
angiography
• Visipaque [iodixanol] vs Omnipaque [iohexol]
– Rate of nephrotoxicity (0.5 mg/dL inc in SCr in 3
days)
• 17/65 (26%) pts in low-osmolar group vs 2/64 (3%) pts in isoosmolar group
– Iso-osmolar better than low-osmolar in high risk pts
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Meta-Analysis
• Reed et al. JACC: Cardiovascular Interventions. 2009;2:645-54.
• 16 PRCT, N = 2,763 patients
• Visipaque (iodixanol) BETTER than
– Omnipaque (iohexol)
– Hexabrix (ioxaglate)
• No difference
– Isovue (iopamidol)
– Ultravist (iopromide)
– Optiray (ioversol)
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Different Contrast Agents
• Normal renal function – non-issue
• Patients at high risk (DM and/or CRI)
–Nonionic, iso-osmolar better than
• Nonionic, low-osmolar better than
–Ionic, high-osmolar
–Or few select non-ionic, lowosmolar (Isovue, Ultravist, Optiray are OK)
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At our hospital
• Radiology/Cardiac Cath/IR
– Optiray (nonionic low-osmolar) OK
– Visipaque (nonionic iso-osmolar)
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BOTTOM LINE
NOT ALL CONTRAST
ARE CREATED
EQUAL!
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Acetylcysteine
• Thiol-containing antioxidant
• Reactive oxygen species may be involved
in pathogenesis of contrast nephropathy
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Prevention of Radiographic-contrast-agentinduced Reductions in Renal Function by
Acetylcysteine
• Tepel et al. (N Eng J Med 2000;343:180-184.)
– Randomized, placebo controlled, single center
– N= 83, patients with renal insufficiency
undergoing radiographic contrast study
– Non-ionic, low-osmolar contrast
– Incidence of contrast nephropathy
significantly lower in NAC group
• 2% vs 21%; p=0.01
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PO Acetylcysteine
•
•
•
•
Cheap
Easy to use
Minimal side effects
Potential benefit
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IV Acetylcysteine
• Used in acetaminophen toxicity
• Minimal toxicity
• Viable option in certain clinical
scenarios?
• Off label use?
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Intravenous Acetylcysteine
• Baker et al. (J Am Coll Cardiol 2003:41(12);2114-2118.)
– Prospective, randomized, open label
– N=80, patients with renal dysfunction undergoing
cardiac cath
– IV NAC (150 mg/kg in 500 cc NS over 30 mins followed by 50
mg/kg in 500 cc NS over 4 hours) vs NS (1 ml/kg/h 12 hrs pre
and post)
– Non-ionic, iso-osmolar contrast
– Incidence of contrast nephropathy significantly
less in NAC group (25% increase in SCr)
• 5% vs 21%; p=0.045
• NAC infusion stopped in 3 patients (itching, rash)
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BOTTOM LINE
NAC only helpful if given
PO >24 hours prior
or…
IV immediately before
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Vitamin C
• Spargias K. et al. Circulation. 2004;110:2837-2842.
– PRCT
– N = 231 patients with SCr >1.2 undergoing CATH
– Ascorbic acid 3 grams 2 hrs before and 2 grams
in the AM vs PLACEBO
– 9% vs 20%
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Prophylactic Hemofiltration
• Marenzi et al (N Eng J Med Oct 2003;349(14):1333-40)
– Randomized, single center
– N=114, patients with CRF (Cr>2) undergoing cardiac
cath
– Hemofiltration vs control (NS, 1 ml/kg)
– Both interventions 6-8 hrs prior and 24 hrs after
procedure
– Non-ionic, low-osmolar contrast
– None in control group received mucomyst
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Prophylactic Hemofiltration
• Less likelihood of increased Cr (>25%
from baseline)
• Less likelihood of requiring temporary RRT
• Decreased in-hospital mortality (2% vs
14%)
• Decreased one year mortality (10% vs
30%)
• Patients with Cr > 4 benefited most
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How about Hemodialysis?
• Vogt et al. (Am J Med 2001;111:692)
– Randomized, prospective
– N=113, high risk patients
– Hemodialysis group more likely to need more
hemodialysis
• Lehnert et al. (Nephrol Dial Transplant 1998;12:358)
– Randomized, prospective
– N=30, high risk patients
No benefit, possible harm
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Sodium Bicarbonate
• Free radicals postulated to mediate
contrast induced nephropathy
• Promoted by acidic environment
• More protective than sodium chloride in
animal models
• Alkalinization of urine may be protective
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• Merten et al (JAMA May 2004;291(19):2328-2334)
– Randomized, single center
– n=119 pts with CRI (Cr >1.1) undergoing cath, CT
scan, or angiogram
– D5W + 154 mEq/L NaCl vs D5W+3 Amps bicarb
(Bolus 3cc/kg 1 hour prior then 1cc/kg/hr for 6 hrs)
– Nonionic low-osmolar, No acetylcysteine
– Incidence of contrast nephropathy less in Sodium
Bicarb group (25% increase in SCr)
• 1.7% vs 13.6% (p=0.02)
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• Brar et al. JAMA 2008
• N = 353 patients with CRI (GFR<60) undergoing
cardiac cath
• Low-osmolar contrast, 48% in each group got
acetylcysteine
Incidence of CIN NO DIFFERENT!
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BICARBONATE
for
Prevention
of
Contrast Induced Nephropathy
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Fenoldopam
• Stone et al. (JAMA 2003;290(17):2284-91)
– Randomized, double-blind, prospective,
multicenter
– N=315, high risk patients undergoing
cardiac cath
No difference in incidence of CIN
U.S. Army Institute of Surgical Research
Lit Search
U.S. Army Institute of Surgical Research
Question
47 y/o man with a 20 yr hx of DM is admitted
with an STEMI. His Cr is 2.8. An emergent
cath is planned. All of the following has
been shown to decrease the risk of contrast
induced nephrotoxicity EXCEPT.
A.
B.
C.
D.
E.
F.
G.
Nonionic Iso-osmolar contrast
Fenoldopam
Oral Mucomyst
IV Mucomyst
Vitamin C
Prophylactic hemofiltration
Sodium Bicarbonate?
U.S. Army Institute of Surgical Research
Why don’t we just get an MRI?
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Nephrogenic Systemic Fibrosis
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Gadolinium
• Nephrogenic systemic fibrosis
– NEW fibrosing disorder with strong
association with GAD (first cases reported in
1997 – now over 300 cases)
– Anyone with a GFR<15 mL/min
– High doses (or repeat doses)
– Vast majority with Gadodiamide (Omniscan)
• FDA black box warning for ALL GAD
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Gadolinium
• Nephrogenic systemic fibrosis
– Majority involve the skin
– Contractures in severe cases
– Fibrosis of other organs (lungs, myocardium,
pericardium, diaphragm, etc…)
• Consider IHD in patients at high risk who
need gadolinium
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True or False?
Continuous Renal Replacement Therapy
is associated with better outcomes
than Intermittent Hemodialysis
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CRRT or IHD?
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CRRT
•
•
•
•
•
•
SCUF
CVVH
CVVHD
CVVHDF
C-SLED
SCD
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Intermittent
•
•
•
•
IHD
SLED/SLEDD
SLEDD-f
EDD
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SLED/SLEDD/SLEDD-f/EDD
• Sustained Low-Efficiency Daily
Dialysis/Diafiltration or Extended Daily Dialysis
• Various hybrid techniques reported in the late
90’s
• Retrofitted outpatient machines used for chronic
HD to allow slower dialysate/blood flow rates
• Treatment over 4-12 hours
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C-SLED/SCD
• Continuous Sustained Low Efficiency
Dialysis
• Slow Continuous Dialysis
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Continuous vs Intermittent
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Lancet 2006;368:379-85.
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Mortality = No Difference
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N Engl J Med 2008; 359:E1.
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ATN Trial: Largest RCT
• ‘High-dose’ CVVH/IHD
– UNSTABLE - CVVH 35 cc/kg/hr (or SLED)
– STABLE - IHD 6x/week
• ‘Low-dose’ CVVH/HD
– UNSTABLE - CVVH 20 cc/kg/hr (or SLED)
– STABLE - IHD 3x/week
N Engl J Med 2008; 359:E1.
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KDIGO
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How about long term (renal)
outcomes?
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KDIGO
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• 13 year retrospective study across Canada
• 2004 CRRT patients matched with 2004 IHD
patients
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ATN Trial vs RENAL Trial
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• Of survivors – 25% needed long
term dialysis
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• Of survivors – 5% needed long term dialysis
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A CRRT-based strategy may lead
to superior renal outcomes
among survivors compared to
IHD.
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True or False?
High chloride containing
crystalloids (NS) are associated
with increased AKI and Death and
should be used with caution.
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Thank You!
[email protected]
U.S. Army Institute of Surgical Research
Respiratory Muscle Physiology and
Bedside Assessment of Work of
Breathing
53nd Annual Weil/UC San Diego Symposium on
Critical Care & Emergency Medicine
(April 11, 2015)
Raúl J. Gazmuri MD, PhD, FCCM
Resuscitation Institute
at Rosalind Franklin University
and
Captain James A. Lovell Federal
Health Care Center
(Section of Critical Care Medicine)
Conflicts
• Funding for research on various aspects of
resuscitation from cardiac arrest and
hemorrhagic shock and role of mitochondria
(DoD, VA Merit Review, Zoll, Baxter, Friends
Medical Research Institute, DePaul-RFU, and
ALGH)
• None related to the current presentation
Outline
• Respiratory muscle physiology (overview)
• Work of breathing
• Loads to overcome
•
•
•
•
Elastic load (ARDS, pneumonia, pneumothorax)
Resistive load (epiglottitis, tracheal stenosis, IAC)
Inspiratory threshold load (intrinsic PEEP)
Inertial load (obesity)
• Recognizing increased work of breathing and
risk of respiratory muscle fatigue
• Clinical clues
• Utility of arterial blood gases
• WOB Scale
Diaphragm
• Contraction lowers the
dome by l-2 cm during
normal breathing and up to
l0 cm during deep
inspiration
• Costal and crural parts; the
costal also expands the rib
cage.
• Responsible for 60-75% of
the lung volume increase.
• Motor innervation is
through the phrenic 3rd, 4th,
and 5th cervical segments.
Ventilation
The relationship between
alveolar pressure and
intrapleural pressure and the
volume of air moved
RESPIRATORY MUSCLE PHYSIOLOGY
• For gas to enter the lungs, a
negative pressure gradient is
required between the alveoli and
atmosphere (or source of gas).
Normal inspiration is active.
• For gas to exit the lungs, a
positive pressure gradient is
required between the alveoli and
atmosphere (or source of gas).
Normal expiration is passive.
WORK OF BREATHING
• WOB (
represents the work
performed by the respiratory muscles to mobilize
gases in and out the lungs to ensure that CO2
removal and oxygen delivery appropriately meet
the metabolic demands
• The WOB at rest is low (<3% resting energy
expenditure); but it increases in proportion to the
inspiratory respiratory loads:
•
•
•
•
Elastic load (ARDS, pneumonia, pneumothorax)
Resistive load (epiglottitis, tracheal stenosis)
Inspiratory threshold load (intrinsic PEEP)
Inertial load (obesity)
WORK OF BREATHING
The Respiratory Muscles
Charis Roussos and Peter T. Macklem
(NEJM 1982;307:786-797)
WORK OF BREATHING
Respiratory Failure
Lung Failure
Pump Failure
Gas exchange failure
(Hypoxemia; dead
space ventilation)
Ventilatory failure
(Hypercapnia)
V/Q mismatch
Central
depression
Mechanical
defect
Demand for WOB
> energy supply
Respiratory muscle
fatigue
INSPIRATORY LOADS TO OVERCOME
Elastic Load: results from decreases in thoracic
cavity compliance increasing the pressure
required to reach a desired lung volume
•
•
•
•
•
•
•
ARDS
Pneumonia
Atelectasis
Pneumothorax
Pleural effusion
Kyphoscoliosis
Intra-abdominal
compartment
syndrome
INSPIRATORY LOADS TO OVERCOME
Resistive Load: results from increases in
inspiratory airway resistance (upper and lower)
augmenting resistance to timely reach the
desired lung volume
•
•
•
•
•
•
•
•
Upper airway trauma
Vocal cord paralysis/spam
Epiglottitis (burn)
Laryngotracheobronchitis
Tube occlusion/kinks
OSA
Asthma/bronchiolitis
COPD
Thumb sign
Steeple sign
INSPIRATORY LOADS TO OVERCOME
Threshold Load: results from air trapping
(intrinsic PEEP) making it necessary for the
inspiratory muscles to lower the alveolar
pressure from the intrinsic PEEP level to below
the pressure at the gas entry level before any
gas moves into the lungs
• COPD
• Asthma
Flow (LPM)
Ins
Exp
Increased compliance
(emphysema)
Decreased compliance
(fibrosis)
INSPIRATORY LOADS TO OVERCOME
Inertial Load: results from increased force to
initiate expansion of the chest cavity and is
closely linked to elastic load.
• Obesity
• Ascites
WOB AND INSPIRATORY LOADS
Intrinsic muscle
capability
•
•
•
•
Elastic
Load
Inertial
Load
Resistive
Load
Threshold
Load
Drive
Mass
Strength
Length-force
Oxygen supply to
inspiratory muscles
• Blood flow
• Hemoglobin
• Oxygenation
Critical • Brain
• Heart
Organ
Perfusion • Inspiratory muscles
WOB AND INSPIRATORY LOADS
• With increased respiratory load there is
proportional increase in WOB and, typically,
tachypnea and recruitment of accessory
respiratory muscles (both inspiratory and
expiratory)
• Increased WOB risks respiratory muscle fatigue
and respiratory failure, which – if not properly
recognized and treated – leads to apnea and
cardiac arrest
• Thus, recognition of increased WOB is important
to promptly institute treatment to prevent further
deterioration
RECOGNIZING INCREASED WOB
• Increase respiratory rate
• Recruitment of accessory inspiratory
muscles
• SCM, scalene, trapezoid, internal
intercostal, nasal flaring
• Recruitment of accessory expiratory
muscles
• Abdominal muscles
RECOGNIZING INCREASED WOB
Rapid Response System
Seizures Syncope Urine
1%
HR 4%
2%
4%
Res Acc Muscles
10%
SO2
20%
Chest Pain
13%
Mentation
13%
Systolic BP
18%
Respiratory Rate
15%
WARNING SIGNS (n = 110) March 2010 – April 2011 RECOGNIZING INCREASED WOB
Recruitment of accessory inspiratory
muscles
RECOGNIZING INCREASED WOB
Recruitment of accessory expiratory
muscles
RECOGNIZING INCREASED WOB
• Loss of diaphragmatic function
• Unilateral: Typically well tolerated
• Bilateral: Relegates the WOB to the accessory
muscles, both inspiratory and expiratory
• Predisposes to respiratory muscle fatigue
• It is often missed at the bedside
BILATERAL DIAPHRAGMATIC PARALYSIS
Neurologic causes Myopathic causes
Spinal cord transection
Limb-girdle dystrophy
Multiple sclerosis
Hyperthyroidism or hypothyroidism
Amyotrophic lateral sclerosis
Malnutrition
Cervical spondylosis
Acid maltase deficiency
Poliomyelitis
Connective tissue diseases
Guillain-Barre syndrome
Systemic lupus erythematosus
Phrenic nerve dysfunction
Dermatomyositis
Compression by tumor
Mixed connective tissue disease
Cardiac surgery cold injury
Amyloidosis
Blunt trauma
Idiopathic myopathy
Idiopathic phrenic neuropathy
Postviral phrenic neuropathy
Radiation therapy
Cervical chiropractic manipulation
BILATERAL DIAPHRAGMATIC PARALYSIS
• Clinical recognition
• Dyspnea upon exercise that worsens in the supine
position (i.e., orthopnea, a symptom frequently
misinterpreted as caused heart failure)
• Onset of orthopnea is dramatic, occurring within
minutes of recumbency, and associated with
tachypnea and rapid shallow breathing
• Tachypnea and paradoxical abdominal wall
retraction (instead of normal protrusion) during
inspiration
• Palpation under the costal margins fails to detect
descending of hemidiaphragms during inspiration
BILATERAL DIAPHRAGMATIC PARALYSIS
Case
•
51 years old female admitted to ICU for emergency
airway management after seizure episode while
having a CT of head, neck, chest, and abdomen
•
Patient has been treated for undifferentiated
adenocarcinoma stage IV without know primary but
with metastasis to brain, neck, mediastinum, lungs,
liver, and one adrenal gland
•
•
Intubation was difficult but eventually successful
Chest-x-ray after extubation showed new bilateral
alveolar infiltrate in the upper lungs not present in
previous chest-x-ray
BILATERAL DIAPHRAGMATIC PARALYSIS
Case
•
Patient regained consciousness while on mechanical
ventilation. Review of imaging studies demonstrated
right frontal lobe metastasis with edema and midline
shift
•
Next morning patient stable and fully awake without
focal neurological deficits and chest-x-ray showed
upper lung infiltrates improving
•
Oxygenation was excellent on PEEP 5 cmH2O and FiO2
0.4
•
Patient was stable and comfortable during
spontaneous breathing trial but f/Vt was 100 attributed
to inability to increase tidal volume
BILATERAL DIAPHRAGMATIC PARALYSIS
Case
•
Because patients was fully awake, willing to be
extubated, and hemodynamically stable she was
extubated having BiPAP available
•
Extubated she had spontaneous breathing with
tachypnea 30 - 40 BPM while maintaining a pulse
oximetry of 100%
•
Given the extensive disease with cervical and
mediastinal involvement the possibility of bilateral
phrenic nerve paralysis was considered
•
Patient indicated she could not tolerate being flat for
months
BILATERAL DIAPHRAGMATIC PARALYSIS
Case
•
Examination showed inward
movement of abdomen
during inspiration and use
of abdominal muscles
during expiration
•
Given the likely possibility
of bilateral phrenic nerve
paralysis, the supine
position was avoided
•
Hypoxemia while laying flat
for the CT examination was
considered as the trigger
for the seizure episode
BILATERAL DIAPHRAGMATIC PARALYSIS
Case
•
Intra-abdominal pressure measured through Foley
catheter revealed decrease pressure during
inspiration confirming bilateral phrenic nerve
paralysis
BILATERAL DIAPHRAGMATIC PARALYSIS
FRC
Normal
Diaphragmatic
Paralysis
RECOGNIZING INCREASED WOB
Utility of arterial blood gases
• Oxygenation best assessed by O2
saturation (e.g., SpO2)
• Respiratory muscle fatigue is late
and life-threatening event
• The goal is to recognize and
manage increased WOB to avert
respiratory muscle fatigue
• Hypercapnia is a late event
Decision needs to be made
based on clinical grounds
without (routinely) asking for
blood gas analysis and/or
waiting for the results
WOB SCALE
• We propose a bedside WOB scale based on a
simple scoring system assigning points to the
respiratory rate and to the activation of specific
accessory respiratory muscles by examining the
nose, the sternocleidomastoid muscles, and the
abdominal muscles
Element
Respiratory Rate
Points
Method of Assessment
<20 = 1
21-25 = 2
26-30 = 3
>30 = 4
Count number of breaths in
20 seconds and multiply by 3
Nasal Flaring
Absent = 0
Present = 1
Observation
Use of Sternocleidomastoid Muscles
Absent = 0
Present = 1
Palpation
Use of Abdominal Expiratory
Muscles
Absent = 0
Present = 1
Palpation
WOB SCALE
Endocrine Emergencies 2
Lori B. Sweeney
VCU Health System
Case 1
 46 y/o male with chronic pancreatitis previously admitted for
DKA admitted s/p seizure with blood sugar of 26 mg/dl per
EMS
 Patient ran out of pain meds
 What is going on?
 By the way, the medicine team reported a sister on a
sulfonylurea and CT scan of the abdomen with “fullness in
the head of the pancreas
 Now what do you think is going on?
Case 1
 Crazy high blood alcohol level
 Very low prealbumin
 Chronic diarrhea
 Pt hasn’t been eating
 Begun on intensive insulin regimen during last admission
Case 1
 Is glucagon likely to be effective?
 How about octreotide 50 mcg q 6-8 hrs IV?
 Blood sugars begin to normalize.....now what?
 Insulinoma = hypoglycemia +plasma insulin level of 3
mcgU/ml or greater, c-peptide of 0.6 ng/ml or greater,
proinsulin of 5 pmol/L or greater, a beta-hydoxybutyrate of
2.7 nmol/L or less, and a rise in glucose of 25 mg/dl s/p
glucagon
Variations on a theme
 What if the patient has breast cancer, on chemo?
 What if the patient is s/p Roux en Y GBP?
 Type 1 diabetic patient with A1C of 5.1%
Differential diagnosis
Impaired gluconeogenesis/glycogenolysis
 Salicylates
 Beta-blockers
 Hepatic Failure
 Renal Failure
 Alcohol
Increased Insulin
 Exogenous Insulin
 Sulfonylurea
 Quinine
 Trimethoprim-sulfamthoxazole
 Alcohol
 Insulinoma
Other
 Insulin receptor antibody, Insulin antibody
 Dumping syndrome
 Autonomic dysfunction
 Adrenal insufficiency
 Growth Hormone deficiency
 Hypothyroidism
Case 2
 64 y/o female with history of primary hyperparathyroidism,
parathyroid exploration with removal of two glands one week
ago
 Precipitant symptoms: fatigue, weakness, abdominal pain,
numbness in hands, feet, and around the mouth, painful
muscle cramps in upper/lower extremities
 Serum Calcium of 6
 EKG: prolonged QT interval
 What other labs do you want?
Hypocalcemia: Differential DX
 Hypoparathyroidism
 Surgical
 Autoimmune
 Magnesium deficiency
 PTH resistance
 Vitamin D deficiency
 Vitamin D resistance
 Other: renal failure, pancreatitis, tumor lysis
Hypocalcemia Work-up
 Confirm low ionized calcium
 History:
 Neck surgery
 Other autoimmune endocrine disorders
 Causes of Mg deficiency
 GI disorders (malabsorption)
Physical Exam Findings
 CHVOSTEK’S SIGN
 Elicitation: Tapping on the face at a point just anterior to the ear
and just below
 the zygomatic bone
 Postitive response: Twitching of the ipsilateral facial muscles,
suggestive of
 neuromuscular excitability caused by hypocalcemia
 TROUSSEAU’S SIGN
 Elicitation: Inflating a sphygmomanometer cuff above systolic
blood pressure
 for several minutes
 Postitive response: Muscular contraction including flexion of the
wrist and
 metacarpophalangeal joints, hyperextension of the fingers, and flexion
of the
 thumb on the palm, suggestive of neuromuscular excitability caused by
 hypocalcemia
FEATURES OF ACUTE vs
CHRONIC HYPOCALCEMIA
ACUTE
 Arrhythmias
 Tetany
 Trousseau’s, Chvostek’s signs
 Seizures (partial or generalized)
 Shortness of breath/stridor
 Acute confusion
 Cardiac Failure
CHRONIC
 cataracts, basal ganglia Ca
 Dementia
 Nail dystrophy
 Papilledema
 Dry Skin
 Cataract
Hypocalcemia Treatment
Tetany, seizures, laryngospasm, cardiac dysfunction:
10-20 mL of 10% calcium gluconate in 50-100 mL 5% dextrose or NS given
over 10 min with ECG monitoring
Repeat until symptom free
Treat hypomagnesemia with IV magnesium sulfate
Start IV infusion of 100 mL of 10% calcium gluconate in 1 L NS or 5% dextrose
at a rate of 50-100 mL/hr
Adjust rate to normalize calcium
Start oral calcium and calcitriol
Case 3
18 y/o male with h/o aML, graft vs. host disease, admitted for
pancreatitis
Consulted to assist with transitiion off the insulin drip
24 hour insulin requirement greater than 300 units
Previous attempts to transition with long acting or intermediate
acting insulin analog plus prandial short acting insulin
unsuccessful
What might be going on?
Case 3
 Graft vs. Host-scleroderma like skin change
 Acquired lipodystrophy
 IV insulin restarted
 Clinical deterioration ensued
 What are we missing
Case 4
 Serum Triglycerides:
> 6000
Case 4
 Chylomicronemia: most often Multifactorial Chylomicronemia
Syndrome
Predisposing genetics plus second hit
Second hit: obesity, DM, drugs: HCTZ, beta-blockers, oral
estrogens, retinoids, atypical antipsychotics, propofol, protease
inhibitors, alcohol
Therapies: fibrates, niacin, omega 3 FA, insulin (direct affects
on lipoprotein lipase), APO-C11 or LPL deficiency: FFP
Diet: FAT only 15% of diet…10-15 grams fat per day
Case 4
 What can we do next?
Plasma
Exchange
(some likely contribution of heparin induced
lipolysis)
Case 4
 74 y/o female with Hodgkin’s lymphoma admitted for altered
mental status, ARF, anemia (hemorrhagic gastric erosion),
recently begun on HCTZ
 Precipitant symptoms: polyuria, “craving for ice chips”,
progressive decline in sensorium over several days,
progressive abdominal pain
 Serum Calcium of 14
 What other labs do you want?
Hypercalcemia: Most common
etiologies
PTH mediated vs. non-PTH mediated
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Hyperparathyroidism
primary
tertiary (underlying chronic renal insufficiency or malabsorption syndrome)
Multiple Endocrine Neoplasia syndrome
Malignancy (in rough order of frequency) squamous carcinoma of the lung
breast cancer
renal cell cancer
head and neck squamous cancer
multiple myeloma
hematogenous and lymphomatous malignancies
Granulomatous disease (in rough order of frequency) sarcoidosis
tuberculosis
leprosy
histoplasmosis/coccidiomycosis
disseminated candidiasis/cryptococcosis
berylliosis
Hypercalcemia: Most common
etiologies
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Hyperparathyroidism
primary
tertiary (underlying chronic renal insufficiency or malabsorption syndrome)
Multiple Endocrine Neoplasia syndrome
Malignancy (in rough order of frequency) squamous carcinoma of the lung
breast cancer
renal cell cancer
head and neck squamous cancer
multiple myeloma
hematogenous and lymphomatous malignancies
Granulomatous disease (in rough order of frequency) sarcoidosis
tuberculosis
leprosy
histoplasmosis/coccidiomycosis
disseminated candidiasis/cryptococcosis
berylliosis
Key components to PE
 Blood pressure
 HR (heart block, bradyarrhytmia)
 Neck exam: lymphadenopathy, neck mass (adenomas are
almost never palpable)
 Don’t forget: the breast exam, rectal exam, mental status
exam (endocrinopathy, paraneoplastic syndrome)
Treatment
 Emergent therapy: calcium greater than 14 mg/dl or > 12.5
mg/dl with symptoms
 Fluid resuscitation is the cornerstone of therapy (most
patients will require 2-4 L in the first 24 hrs)
 In general, fluids + furosemide + bisphosphonate
 Calcitonin is reserved for severe hypercalcemia (due to time
course of bisphosphonate therapy)
Therapy cont.
 Goals of correction: IVFs should decrease the serum
calcium by 1.5-3 mg/dl in 24-48 hours
 Do not use furosemide until adequate volume expansion
 Dosing of Lasix: lower dose in naïve patients, young
patients, higher dose often needed in patients with CV
dysfunction
 Monitor electrolytes especially if diuresis is brisk
The Issue with Furosemide RX
 Natriuretic effect >> calciuretic effect
 So without adequate volume resuscitation, the volume status
will worsen
 It has largely reserved for patients with heart failure in whom
the volume resuscitation is likely to be problematic
When to use glucocorticoids
 Hematologic malignancy (lymphoma or myeloma)
 Granulomatous disease (sarcoidosis, Vitamin D intoxication)
 - given IV in a dose of 200 - 300mg/day of hydrocortisone (or
its equivalent) for 3 - 5 days
 Effects are often delayed for a couple of days
Bisphosphonates cont.
 Pamidronate: older preferred agent
 In general: 60 mg over > 4 hours for a serum calcium < 14
mg/dl (< 3.5 mmol/L), 90 mg infused over 90 minutes to 6
hours > 14 mg/dl
 Zolendroic Acid IV, 4 mg in 100 mL 0.9% saline over 15-30
minutes
 Ibandronate IV, 6 mg in 100 mL 0.9% saline over 15 minutes
Therapy
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Calcitonin:
Good option in renal failure
Low potency
Mechanism of action: decreases bone resorption and promotes urinary
clearance of calcium
Also has anlagesic properties
Used routinely if calcium is >16 mg/dl, tachyphylaxis occurs within a
few days…but will “bridge” to bisphosphonates
Glucocorticoids potentiate the effects of calcitionin and decreases the
escape phenonmenon
Salmom-calcitonin: 4 units/kg sc/IV every 12 hours (1 unit skin test)
Synthetic human calcitonin: 0.5 mg sc daily
Time course: an effect will be seen within a few hrs, nadir at 12-24 hrs
Hypercalcemia in renal failure
 Dialysis with zero calcium bath
 Etiology may be the vitamin D supplementation
Case 5
 Called to see 50 y/o female with T1DM on insulin pump
therapy admitted for psychosis
 No suicidal ideation
 Last blood sugar 140 mg/dl
 What would you do?
Contraindications for pump therapy
 Altered state of consciousness
 Patient at risk for suicide
 Critical illness
 Inability of patient or family member for management of CSII
 DKA or hyperglycemic hyperosmolar state at admission
Case 5
 One to one nurse
 Pt would not allow me to access the pump
 Reported she last filled reservoir two days ago
 Called risk management
Judicial order
required to
remove pump
Case 5
 Clarify with your institution, before it happens
 Tubing can but cut
 One-on-one, to see if the patient manipulates the pump
 In a type 1 patient, the continuous infusion rate should keep
the patient out of DKA, but sometimes is set too high for a
non-fasting state, so low blood sugars may occur if patient is
NPO
Questions?
Elderly Trauma:
Pitfalls and Lessons Learned
Kaysie L. Banton, MD
UMMC Trauma Medical Director
Fairview System Trauma Medical Director
Case Scenario
●
A 76-year-old male is brought to the ED after he
fell from a ladder while cleaning his gutters.
Prior to falling, felt dizzy. On Coumadin for
recent MVR. Lethargic, MAE, garbled speech.
●
Initial vital signs: RR 32, Pulse 86, BP 146/86,
GCS score 12
Objectives
• Understand physiology differences
• Review injury patterns
• Special considerations
Aged Definitions
• Trauma Old = 35 years
• Elderly = Over age 65 years
• Young old = 65-80 years
• Old old = Over age 80 years
The Problem of Trauma
• 7th leading cause of death >65yo
– Currently 13% of population
– 32% injury related hospitalizations
– 33% injury related deaths
• Grey Tsunami coming – 2030
– 1/5 of population will be >65yo
– 14 million >85yo
Unique Trauma
• Falls
Leading
Causes
of Injury
• Motor vehicle
crash
• Alcohol
• Burns
• Pedestrian vs.
vehicle
Geriatric Trauma
• Falls are the most common mechanism
– 40% of elderly trauma
– 3.8% have a significant fall each year
– 55% mortality
• Most occur at home from ground level
• Even isolated hip fractures are significant
– 32% die within 12 months of fall
• 25% of falls due to underlying medical
problem
Unique Characteristics
What are the unique characteristics of
geriatric trauma?
Aging Differences
•
Effects of age:
–
Anatomy
–
Physiologic functions
–
Comorbidities
–
Medications
Unique Characteristics
↓
↓
↓
↓
↓
Brain mass
Diminished hearing
Eye disease
↓Sense of smell and taste
↓Saliva production
↓Esophageal activity
↓Cardiac stroke volume and rate
Depth of perception
Discrimination of colors
Pupillary response
Renal function
2- to 3-inch loss in height
Impaired blood flow to leg(s)
↓
Degeneration of the joints
Total body water depletion
Nerve damage (peripheral
neuropathy)
Stroke
Heart disease and high blood
pressure
Kidney disease
↓Gastric secretions
↓Number of body cells
↓Elasticity of skin, thinning of
epidermis
15 – 30% body fat
ATLS - Primary Survey
• Airway
– with c-spine protection
• Breathing
– Oxygenation and ventilation
• Circulation
– And hemorrhage control and vascular access
• Disability:
– Neurological deficits
• Exposure / Environment
– Elements at scene (chemicals, temperature), removal of
clothing and hypothermia prevention
Airway/Breathing changes with
aging
Airway Pitfalls
• Factors affecting airway management
• Dentition (including dentures)
• Nasopharyngeal mucosal fragility
• Cervical arthritis
• Arthritic joints including Mandibular joints
Decreased cardiopulmonary reserve may require
early intubation
Pulmonary changes with aging
Chest changes with aging
• Decreased:
–
–
–
–
Airway clearance/ cough
Laryngeal reflexes
Mucociliary clearance
Number of Alveoli
• Reduced elastic recoil
of lungs/chest wall
– Reduced chest muscle
strength
• Increased V/Q
mismatch
• Increased risk:
– Increased aspiration risk
– Infection
• Decreased response to
hypercapnea
• Arterial hypoxemia
– Ave PaO2 78-92 mmHg
Unique Breathing Changes
• Respiratory
– Lung less compliant
– VC, FEV1, PaO2 decrease with age
– Muscles of respiration weaker in the elderly
• Airway management may be affected by changes
with aging
– Difficult intubation secondary to neck/jaw mobility
– Chest wall more rigid and brittle
– More prone to traumatic injuries
Breathing Pitfalls
• Diminished respiratory reserve
• Use of supplemental oxygen
• Comorbidities:
• COPD/Asthma,OSA
• Chest injuries poorly tolerated
“Minor” chest injuries have major effects
Rib Fractures in the elderly
• Often have associated head injury
• Common cause of readmission to ICU
– 10% mortality
– 1:1 relationship to complication
• Aggressive pulmonary toilet
• Pain
– Blocks (indwelling vs injection)
– Non-narcotic
– Epidural
– Consider rib fixation
Unique Circulatory Problems
• Decreased cardiovascular function and reserve
• Preexisting CHF
• Cautious fluid administration
• Anticoagulants and other medications
• Pharmacologic effects
• Catecholamine effects and dysrhythmias
Unique Cardiovascular Issues
• Inadequate cardiovascular response to
trauma
– Occult shock
– Less cardiovascular reserve
– Respond to hypovolemia with increased SVR vs.
increased CO
– Unable to tolerate and respond to fluctuations in
blood volume
• Become hypothermic easier/faster
Unique Circulatory Problems
Unique Circulatory Problems
• Blunted baroreflex and altered b-adrenergic
responsiveness
– decreased dependence on chronotropy
– increased reliance on stroke volume in response
to stress
• Atrial Fibrillation
– Common Chronic comorbidity
– Common acutely as reaction to stress
• No superior treatment
• Resume BB if previously taking
Circulatory Pitfalls
• Elderly trauma patients are at higher risk
– Less compliant vessels
– Preexisting CAD
– With increased HR, less diastolic filling of
coronary vessels
– Increased turbulent flow = decreased coronary
perfusion
Circulatory Monitoring
• NIBP
– Skin at risk
• CVP
– Limitations
• Pulse wave (FloTrac)
– Limited in peripheral arterial disease
• Use compilation of measures
Circulatory Support
• Colloid not better than crystalloid
– Small volumes
– Hemorrhagic shock – transfuse early
• Optimization of fluid status may fail to correct
hypoperfusion
– Dobutamine can cause tachycardia increase in
myocardial oxygen demand precipitating AF
– Milrinone (nonadrenergic MOA), but less
effective
– NE/Vasopressin common
Unique Neurologic Characteristics
• Central nervous system
– Dura adherent to inside of skull
• Brain atrophies
– More tendency to move inside skull during
trauma
– More likely to develop CNS bleeds
• Spinal stenosis / DJD complicates
evaluation
Unique Neurologic Characteristics
• Acute and chronic subdural
hematomas
• Altered sensorium
secondary to cerebral
atrophy, hypoperfusion, and
medications
• Spinal osteoarthritis, leading
to frequent spinal column
and cord injuries
• Neuropathy
Neurologic Pitfalls
• Baseline dementia
• Comorbid neuropathy/deficits
• Narcotic use
Unique Exposure Characteristics
• Abnormal thermoregulatory
mechanism
• Increased sensitivity to hypothermia
• Increased risk of infection
• Lack of tetanus protection
Geriatric skin and soft tissue
• Thinning, loss of dermal appendages
increase the risk of injury and impair wound
healing
• Minor trauma results in large hematomas,
skin tears and sloughing
• More prone to pressure ulcers after short
time on back boards
– 30 mmHg/30min (may be much shorter for
malnourished thin elderly patient)
Elderly and Burns
• Higher risk
• Lower rates of healing
– Fewer hair follicles
– Hypertrophic scarring
• Burn healing is running a marathon
– LD50 at 80y is 8%
Unique Musculoskeletal
Characteristics
• Structually
– Osteoporosis
– More prone to fractures
– Decreased mobility of joints
– Spinal column problematic
• Less circulating catecholamines
• Poorer balance
• Vision problems
Musculoskeletal Pitfalls
• Most frequent cause of morbidity
• Susceptible to certain fractures
• Hip fx - 1%/year in men and 2%/year in
women over 85 years of age
• Osteoporosis
• Preexisting deformities complicate evaluation
• Immobility will lead to complications
Unique Renal Characteristics
• Reduced renal blood flow
– 10% per decade after age 40
• Reduced glomeruli (replaced with fibrosis)
– loss of 30-50% by age 70
– Medullary hypotonicity and increased water loss
– Hyponatremia
• Tubular frailty
– Sensitive to nephrotoxic/hypoxic insult
Aging kidneys and AKI
• Higher risk of contrast induced nephropathy
– No benefit of pre-exposure bicarb or Mucomyst
• No particular treatment better
• If requires acute RTT
– Same indications
– Same options
– Same outcomes for renal recovery
– 14.29% likelihood of initiating RRT within 2 years
Recommendations
• MAP >60 to promote renal perfusion
• Mortality rates higher if
– Hospital 15-40%
– 2 year mortality 28.2%  57.7%
– 14.29% likelihood of initiating RRT within 2 years
Injury Patterns – think fragility
• Pedestrian vs MVC
– Ribs, head, long bone
• High speed MVC
– Head, Ribs/sternum, Aortic dissection, long
bone
• Fall from height
– Rarely landing on feet: head, chest, pelvis,
ribs
• Fall from standing
– Head, hip, ribs
Mortality
• After controlling for Injury Severity Score,
Revised Trauma Score, preexisting disease,
and complications, the elderly were 4.6 times
as likely to die.
– directly related to trauma (40.9%)
– likely related to trauma (31.8%)
– unrelated to trauma (27.3%)
– Admitted to ICU? Higher mortality at 1 year
Early predictors of death
• elderly trauma patients >55y
• ABG <1 hour of patient admission
– Predictor of ICU length of stay and mortality
– Base deficits mild ( 3-5), moderate ( 6-9), and
severe (10)
• Severe BD had 80% mortality
• Moderate BD had 60% mortality
• Even a “ normal” base deficit carried a
mortality of 24%
Early predictors of Death
• Base deficit < 6 is particularly ominous in
elderly trauma patients
• SBP <90 mmHg is associated with an 82%
mortality rate
Geriatric Physiology
• Older adults respond to trauma differently
than their younger counterparts
– More occult hypoperfusion
• Comorbid conditions
• Polypharmacy
– Beta-blockers, calcium channel blockers,
diuretics, narcotics
Occult Shock
• Inability to maintain organ perfusion
• Use base deficit, lactate as resuscitation
measure
• Early use of invasive monitoring
• Judicious use of vasopressors to augment
CO
Triad of Death
Approach to the Geriatric Trauma
Patient
• BP
– May be deceivingly normal
– Many patients with underlying hypertension
– Increasing SVR in response to hypovolemia
• Pulse
– May be falsely normal
– Medication effects, blunted catecholamine
response
Approach to the Geriatric Trauma
Patient
• Laboratory
– Serial hematocrit or hemoglobin
– Consider resuscitating to LA or base deficit levels
(Q6h)
• Low threshold to transfuse
–
–
–
–
PT / PTT
Serum electrolytes
Rapid glucose
Medication levels
• EKG
Trauma Physiology
• Immediate disruption in thermoregulation
– Keep the patient WARM
• Cardiac contusion uncommon
– If initial EKG normal, no additional work up needed
• SOB can mean many things
– Pulmonary contusion, hemorrhage, sepsis, COPD,
airway compromise, CHF
• Hypotension should still be presumed to be
hemorrhage
The Geriatric Trauma Patient
• >80yo TBI requiring craniectomy
– Sim 30d mortality, outcomes, more resources
• >65yo, nl GCS >2% risk of requiring neurosurgery,
>5% if anticoagulated
– PCC reversal = shorter ICU time
• Older patients (>65-70) probably better outcomes
at Trauma Centers regardless of injuries
– Can manage non-op spleens just like younger patients
– Dedicated geriatric trauma unit has better outcomes
– Older with severe TBI (GCS <8) who don’t improve at
72h should move to comfort cares
Aging and Trauma
• >45yo: increased fatality, end organ failure,
coagulopathies
• 45-65 increased infections
• fewer infections >65
• Anticoagulation is more likely to cause SDH with any
trauma
– not associated with recurrence rates, but recurrence onset
• Specific Therapeutic Approaches
– Intranasal insulin helps with cognitive impairment
recovery
– Geriatric protocols improve outcomes
ATLS - Primary Survey
• Airway
– Remove dentures, careful with mouth opening, c spine
• Breathing
– 100% Oxygen, sats of 91% may be patients baseline
• Circulation
– Poor circulation, vascular disease, CAD, BB, CCB
• Disability:
– Neurological deficits vs neurological baseline,
neuropathy
• Exposure / Environment
– Hypothermic, move off of hard surfaces immediately
Recommendations
• All trauma patients over age 55 should be
considered for evaluation in a trauma center
– lower threshold for trauma activation should be
used for injured patients aged 65
• Physiologic age more important than
chronologic age in approaching patients
– Frailty score
Special Issues
What are the special issues to
consider in treating geriatric trauma
patients?
• Medications
• Elder maltreatment
• End-of-life decisions
Drugs That Affect Resuscitation
• Beta blockers
• Corticosteroids
• Antihypertensives
• Diuretics
• NSAIDS
• Hypoglycemics
• Anticoagulants
• Psychotropics
• Alcohol
Recognizing Elder Maltreatment
• High index of suspicion
• Patterns of injury
• Multiple types
• Physical maltreatment
• Sexual maltreatment
• Neglect
• Psychological maltreatment
• Financial and material exploitation
• Violation of rights
Strategy For Elder Maltreatment
• Don’t query in presence of possible
abuser.
• If maltreatment is suspected, remove
patient from abusive environment.
End-of-Life Decisions
• “When is enough, enough?”
• Advance directives?
• Right to self-determination is paramount
• Treatment only in patient’s best interest
• Benefits of treatment outweigh adverse
consequences
Case Scenario
●
A 76-year-old male is brought to the ED after he
fell from a ladder while cleaning his gutters.
Prior to falling, felt dizzy. On Coumadin for
recent MVR. Lethargic, MAE, garbled speech.
●
Initial vital signs: RR 22, Pulse 86, BP 146/86,
GCS score 12
What should you consider
in management of this patient?
Summary
●
Trauma in the elderly is increasing
●
Treatment priorities are the same
●
Remember anatomic and physiologic changes
●
Comorbid conditions and medications
●
Consider elder maltreatment
●
Early conversations about goals of care
Questions?
4/13/2015
The ProCESS,
ARISE and Promises Trials
Optimization Trials
“A Closer Look”
Late
Early
Mortality
(Boyd, New Horiz, 1996)
(Kern, Crit Care Med, 2002)
1
4/13/2015
POST-RESUSCITATION
INTENSIVE CARE PROTOCOL
Fluids:
PCWP:
Hgb:
MAP:
Renal:
Inotropes:
Preload:
Afterload:
Pressors:
D02:
V02:
Vent.:
crystalloids and colloid
above 18 mm Hg
10 g/dl
greater than 70 mm Hg
dopamine 2 ug/kg/min
dobutamine
nitroglycerin
sodium nitroprusside
norepinephrine (4 mg/250 ml NS)
600 ml/min.m2
120 ml/min.m2
Controlled Mechanical Ventilation
Am J Cardiol, 1998
2
4/13/2015
Am J Emerg Med 1996
The Evolution of Early Sepsis Care
NEJM, 2014
NEJM, 2014
What’s is Early Sepsis Care in 2015?
3
4/13/2015
Who and what do you believe?
What’s the best thing to do for my next
patient?
4
4/13/2015
Curative and Palliative Approaches to Care throughout a Critical Illness.
SIRS and Lactate
Antibiotics
Sudden CP Collapse
Delayed EGDT
EGDTProCESS Enrollment
Admission
to ER
Admission
to ICU with 2 hours
Cook D, Rocker G. N Engl J Med 2014;370:2506-2514.
Enrollment and Center Description
5
4/13/2015
Antimicrobials had to be commenced
prior to randomization.
Crit Care Med, 2014
8.5% Increase in Mortality
The lactate screening and risk
stratification:
Its impact on mortality
6
4/13/2015
Outcome Impact of
Lactate Measurements
51.4 to 29% (11.4%) - No Hypotension
58.6 to 44.5% (12.1%) - Hypotension
Prevention of
Sudden Cardiovascular Complications
Outcome - EGDT
Rivers et al.
Rivers E, Nguyen HB, Havstad S et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock.
N Engl J Med 2001;345:1368-77.
7
4/13/2015
12.1% of All
Cardiac Arrests
Hemodynamic Phenotyping of Sepsis
8
4/13/2015
Inflammatory Mediators Produce Cardiovascular Insufficiency
Increased Metabolic Demands:
Fever, Tachypnea
Hypovolemia,Vasodilation &
Myocardial Depression
Microvascular Alterations:
Impaired Tissue Oxygen
Utilization
Cytopathic Tissue Hypoxia
Fink, Crit Care Clin, 2002
MAP
Cardiac Index
CVP
ScvO2
Was there equipoise:
Were the centers practicing
standard care?
9
4/13/2015
“In summary, our results suggest that usual resuscitation may have
evolved over the fifteen years since the Rivers’ study and that NHS
hospitals now achieve similar levels of in-hospital survival to those
achieved with EGDT in the Rivers’ study for patients with early
septic shock – if they are identified early and receive intravenous
antibiotics and adequate fluid resuscitation.”
Comparing the screen and risk
stratification between ProCESS and EGDT
10
4/13/2015
Can this be adequately
recommended based on the study?
Central line placement
The ProCESS Investigators. A randomized trial of protocol-based care for early septic shock. NEJM 2014; March 18 Epub
11
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Late
Early
999,949
203,481
12
4/13/2015
Early
Late
Age-adjusted
hospital mortality
declined from 40.4%
in 1998 to 31.4% in
2009
13
4/13/2015
Does delayed care influence
outcomes
14
4/13/2015
2011
Does protocolized care
decrease mortality?
15
4/13/2015
The Changing Landscape of
Sepsis Mortality:
Are we getting better at
sepsis management?
EGDT after More Than a Decade at HFH
Mortality %
NEJM, 2001
51%
46%
30%
15%
November 8, 2001
Pre-EGDT
EGDT(2001)
Cumulative Studies
ProCESS
Control
EGDT
2015
N
Before or Control
N
After
130
46.5%
133
30.5%
12,456
46.8 (26)%
14.567
29.1 (12) %
?
18-20%
16
4/13/2015
Baseline Hemodynamics:
What do they tell you?
Stage
Hemodynamic Picture
SBP
Hypovolemia
B
Myocardial Suppression
A
Resuscitated, compensated and
vasodilatory
C
Supranormal DO 2 dependency
D
Impairment of tissue O 2 utilization
CVP
Treatment and Comments
↓
Variable
↑
Variable
↑ to normal
Volume
Correct anemia, Inotropic
Therapy
Vasopressors, low dose
corticosteroids
Increased VO2 after
augmentation of DO 2
Variable
Decreased VO2
r-APC
Resuscitated
Heterogeneity in Hemodynamic
Optimization
17
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18