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11/5/2013
Septic and Pregnant: a practical approach to diagnosis and treatment
Laura E. Riley, MD
Massachusetts General Hospital
Division of Maternal Fetal Medicine
November 6, 2013
Objectives
Following this lecture, participants should be able:
1. To recognize signs of early sepsis
2. To develop a differential diagnosis for sepsis in pregnancy
3. To initiate early treatment for sepsis
Definitions
• SIRS ‐ systemic inflammatory response syndrome
• Sepsis – organ dysfunction, hypo‐perfusion or hypotension
• Septic shock – sepsis induced hypotension despite resuscitation with perfusion abnormalities or acute mental status changes
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The Host Response in Severe Sepsis
Angus DC, van der Poll T. N Engl J Med 2013;369:840-851
Organ Failure in Severe Sepsis and Dysfunction of the
Vascular Endothelium and Mitochondria
Angus DC, van der Poll T. N Engl J Med 2013;369:840-851
Epidemiology of Sepsis
• Incidence is 240‐300 cases/100,000 population
• More than 750,000 cases per year
Martin et al NEJM 2003:348;1546‐54
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cdc.gov
Epidemiology of Sepsis
ICU patients with sepsis
• 62% with gram‐neg bacteria
• 47% with gram‐pos bacteria
• 18% with fungi
Half of all sepsis cases: pneumonia
Then intra‐abdominal infections & UTI
Vincent et al. JAMA 2009;302:2323‐9
Angus et al. NEJM 2013;369:840‐51
Resources / Cost
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Average LOS – 75% longer for sepsis cases
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Average LOS – even for <65 yrs double the norm
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Eight times more likely to die
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2008 Inpatient cost ~ $14.6 billion in 2008
cdc.gov
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Epidemiology of Sepsis in Pregnancy
• In the US, sepsis in pregnancy is rare (0.002‐
0.01% of deliveries).
• In the US, serious acute maternal morbidity 0.4‐
0.6 per 1,000 pregnancies
• In UK, mortality rate related to sepsis increased from 0.85 deaths/100,000 pregnancies in 2003‐5 to 1.13 deaths in 2006‐8.
Case 1
• 34 yo G3P2 @ 17 wks gestation w/intact membranes c/o fever and ‘not feeling well’ • Pertinent History:
– LEEP x 3
– Prior C/S x 2 and anterior placenta
– Cerclage placed 12 days prior
– Urine cx @ first visit negative
Case 1 (cont.)
Over next 6 hours:
increase in fever, fetal demise, cerclage removed, laminaria placed, rigors
VS: 90 /50 (baseline 90/60) P: 120 RR: 30 T: 102°
WBC: 12.6 8.7 Hct: 32.6 25.1 Plt:168K  110K
Na:132 K: 3.2 Bicarb: 18.7 BUN: 8 Cr: 0.46
Tx to ICU and is immediately intubated.
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Risk factors for sepsis
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Obesity
Impaired glucose tolerance/diabetes
Anemia
Vaginal Discharge
History of Pelvic infection
History of GBS
Amniocentesis and other invasive procedures
Cerclage
Prolonged spontaneous rupture of membranes
GAS in close contacts/family members
Of Black or other minority ethnic group origin
RCOG Guideline‐Bacterial Sepsis in Pregnancy‐2012
Clinical Features Suggestive of Sepsis
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Fever or rigors
Diarrhea or vomiting
Rash
Abdominal/pelvic pain and tenderness
“Offensive” vaginal discharge
Productive cough
Urinary symptoms
RCOG Guideline-Bacterial Sepsis in Pregnancy-2012
Is this pregnant patient septic?
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Signs and symptoms
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Fever
Temperature instability ( >38° or < 36°)
Tachycardia (>110beats/min)
Tachypnea (>24 resp per min)
Diaphoresis
Clammy mottled skin
Nausea or vomiting
Hypotension or shock
Oliguria or anuria
Pain Altered mental state ( confusion, decreased alertness)
Adapted from Barton and Sibai Obstet Gynecol 2012
Laboratory findings
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Leukocytosis or leukopenia
Positive culture from infection site and /or blood
Hypoxemia
Thrombocytopenia
Metabolic acidosis (increased serum lactate, low arterial pH, increased base deficit)
Elevated serum creatinine
Elevated liver enzymes
Hyperglycemia in the absence of diabetes
DIC
Adapted from Barton and Sibai Obstet Gynecol 2012
Early Identification of Sepsis
• Consider sepsis if 2 or more of following:
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Systolic BP < 90
Mean arterial pressure < 65
HR > 110
WBC > 12,000 or < 4,000 or bands > 10%
Temp > 38 ⁰Cor<36⁰C
De Swiet’s. Medical Disorder in Obstetric Practice. 2010.
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Evaluation, Prophylaxis and
Treatment Guidelines of Febrile
Women in Obstetrics (2013)
Evaluation
For all patients (antepartum, labor and delivery, or postpartum) who have fever ≥101ºF, initiate a work up (regardless of prior antibiotic use) to consist of:
Blood cultures (2 sets)
Urine culture and urinalysis (obtain specimen by catheterization)
Evaluation of other fluids as appropriate (e.g., amniotic fluid1, drainage from incision sites, cultures from wound or intraabdominal collections)
Aerobic cultures
Anaerobic cultures
Gram Stain
CBC with differential count
Chem 7
If this is a new postpartum fever, notify nursery of maternal temperature and ask that pediatrician be notified of maternal fever
Severe infection/ sepsis should be considered for all patients (antepartum, labor and delivery or postpartum) with fever > 101 plus at least one of the following:
HR ≥120/min, sustained over 30 minutes or more
RR≥20/min, sustained over 30 minutes or more
WBC ≤4000 or ≥20,000 ≥10% bands on the manual WBC differential
MAP ≤65
BP ≤90/60, sustained over 30 minutes or more
New rash
Evaluation should consist of work up for fever > 101 plus:
Venous Lactate
Evaluation for multisystem disease: Coagulation studies (DIC panel), LFTs, consider ABGs if there is a persistent tachypnea.
STAT Anesthesia evaluation/consult
Infectious Disease consult SICU consult Suggested Management
In Labor: Consider expedited delivery; consult other obstetrician (high risk if available)
On Post Partum floor: Transfer to Labor and Delivery or SICU for intensive monitoring
ANTIBIOTICS while awaiting Infectious Disease consult recommendations:
If the pathogen is known, tailor antibiotics for optimal coverage.
For empiric coverage, use vancomycin 1 gm IV q12h plus imipenem/cilastatin 500 mg IV q6h. If preeclampsia or pregnancy induced hypertension (PET/PIH) have been previously diagnosed during this intrapartum/postpartum course or seizure history use meropenem 1 gm IV q8h pending ID consultation
If severe penicillin allergy or carbapenem allergy, use vancomycin 1 gm IV q12h plus aztreonam 2 gm IV q8h plus clindamycin 900 mg IV q8h or metronidazole 500 mg IV q8h
Prophylaxis
C/S Prophylaxis
Ancef 2 grams within 1 hour of skin incision
***Repeat Ancef 2 grams if case is greater than 4 hours or blood loss greater than 2 liters
If PCN allergy ( anaphylaxis or worse), give Clindamycin 900mg IV and Gent 120 grams IV within 1 hr of incision.
If PCN allergy (rash or unknown), give Ancef 2 grams IV within 1 hour of skin incision.
Sab for D and E
Doxycycline 100mg IV on call for D and E
Doxycycline 200 mg po post procedure
Manual Extraction of placenta
No antibiotics are needed. No data to support its use particularly as the antibiotics are generally given after the highest risk for bacterimia i.e. during the extraction. Retained Placenta Ancef 2 grams on call to OR for D and E
Treatment
Intraamniotic infection
For presumed IAI based on temp > 100.4 give Ampicillin 2 gm IV q6h plus gentamicin 2 mg/kg IV x1 loading dose, then 1.7 mg/kg IV q8h for patients with normal renal function.
If SVD, discontinue antibiotics after delivery. For presumed IAI based on temp > 100.4 and going for C/S: continue abx as above – note in the chart that prophylaxis not given due to prior abx for IAI and consider adding Clindamycin or Flagyl for better anaerobic coverage. Post C/S, continue antibiotics until 48 hours afebrile ( <100).
For patient receiving GBS prophylaxis who then develops fever (>100.4), add Gentamicin to Ampicillin. Endometritis
***Evaluation to occur if temp > 101 OR known Group A Strep or MRSA, new rash, indwelling hardware or “toxic” appearing but temperature less than 100.4‐101.
Unasyn ( Amp/sulbactam) 3 grams IV Q 6 hrs until 48 hours afebrile. No PO antibiotics needed. If PCN allergy, Clindamycin 900mg IV and gentamicin 2 mg/kg IV x1 loading dose, then 1.7 mg/kg IV q8h for patients with normal renal function.
www.ccmjournal.org Feb 2013, Vol 41(2)580‐637.
Dellinger et al. www.ccmjournal.org Feb 2013;41;580‐637
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Case 1 (cont)
• Fluid resuscitation, broad spectrum antibiotics, intubation
• Empty the uterus ‐‐‐ hysterotomy • Placenta accreta and DIC
• TAH, 22 units of blood and FFP 1:1
• Uterus packed day 1, re‐op for bleeding day 2, day 3 packs removed and vac dressing • D/C to home day 8 Maternal Outcomes
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ICU admission
Pulmonary edema
ARDS
Shock liver
Septic emboli to other organs
Myocardial ischemia
Cerebral ischemia
DIC
Death (20‐23% with septic shock & organ failure)
Adapted from Barton and Sibai Obstet Gynecol 2012
Neonatal outcomes
• Preterm delivery
• Neonatal sepsis
• Perinatal hypoxia or acidosis
• Fetal or neonatal death
Adapted from Barton and Sibai Obstet Gynecol 2012
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Management hinges on:
• Early detection
• Prompt intervention
• ICU transport
Resuscitation
Hemodynamic management
Antibiotics
Fetal assessment
Delivery or eliminate source of infection
Case 2
18 yo G 1 P 1 delivered at 39 weeks
Labor was uncomplicated; 1st degree laceration
Discharged on POD #2 Returns to clinic with complaint of copious vaginal discharge and malaise
• Arrives: BP 90/50 P 100 T 103°
• Toxic appearing, non‐focal exam except erythema of vagina and copious clear discharge
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Mgmt for Suspected Sepsis
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Increase frequency of vital signs
Urine output monitoring
Large bore intravenous access
Blood & Urine cultures before antibiotics
Antibiotics within 1 hour Labs
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Complete blood count/ differential
Electrolytes
AST/liver function
Lactic acid
De Swiet’s. Medical Disorder in Obstetric Practice. 2010.
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Causes of Sepsis & Septic Shock
• Acute Pyelonephritis
• Retained POCs • Undertreated chorioamnionitis or endomyometritis
• Pneumonia (bacterial or viral)
• Unrecognized or inadequately treated necrotizing fasciitis
• Intraperitoneal etiology ( non‐obstetric)
Adapted from Barton and Sibai Obstet Gynecol 2012;120:689‐706.
Potential Offending Organisms:
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Group A strep
Group B strep
E. Coli
Clostridium
Other gram negative organisms
Other anaerobes
MRSA
Viruses ( influenza, varicella)
Go Big and go fast!
• Broad spectrum antibiotics pending culture results
• Drain any and all collections including emptying the uterus
• Combo favorites: Amp, Gent, Clinda ok but Vancomycin plus Imepenem/cilastatin or vancomycin plus meropenem or vancomycin, aztreonam plus clindamycin.
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GAS Toxic Shock Syndrome
– Exotoxins ac vate immune system →↓ inflammatory cytokines → capillary leak and ssue damage → shock and organ failure
– Estimated 3.5 cases/100,000 persons with case‐
fatality rate =36%
– Affects persons of all ages
– Risk factors: minor trauma, injury, surgery, viral infection (varicella), NSAIDS
GAS Necrotizing Fasciitis
• Main portal: skin following trauma or surgery
• Associated conditions: drug use, diabetes, obesity, immunosuppression
• Rapid progression and extensive destruction
• Rx: aggressive debridement, clindamycin + PCN
CDC Surveillance Data on GAS (2007‐2009)
Total
Bacteremia
Overall no. (%)
Pregnant (%)
PP (%)
Nonpregna
nt (%)
439
25 (6)
65 (15)
349 (80)
141 (32)
8 (32)
25 (38)
108 (31)
Endometritis
23 (5)
0
23 (35)
0
Pneumonia
53 (12)
2 (8)
1 (2) 50 (14)
High case
fatality syndrome***
273 (62)
14 (56)
31 (48)
228 (65)
40 (9)
0
1 (2)
39 (11)
Died
Deutscher et. Al. CID, 2011
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Case 3
• 52 year old G2 P2 presents 18 days postpartum with fever to 101.4° and shaking chills
• Pertinent history:
• DVT during IVF embryo transfer
• Cesarean delivery complicated by delayed PPH
– 3 L hemoperitoneum
– Large abdominal wall hematoma
• Wound infection  wound vac
Case 3 (cont.)
• V/S: 101⁰F 115/60
110 24
• PE: Wound with nl granulation tissue
• Pertinent lab data:
– HCT 30.1%
– Wbc 20.1 with 18.2 N
– Plt of 724K
– Normal chem 7, normal LFTs
C. Dificile Pathogenesis
• Antibiotic therapy
• Disruption of colonic microflora
• C. dificile
exposure and colonization
• Release of toxin A and B
• Mucosal injury and inflammation
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C. Diff Associated Diarrhea (CDAD)
• Watery diarrhea (10‐15 x/day)
• Lower abdominal cramping
• Low grade fever
• Leukocytosis
• May start during antibiotic therapy • or 5‐10 days post therapy
CDAD → Coli s
• Diarrhea ± blood
• Severe lower quadrant pain
• Abdominal distention and fever
• Leukocytosis and lactic acidosis
• Complications: toxic megacolon, bowel perforation, death (all have been reported in peripartum patients)
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Treatment of Fulminant Colitis
• Discontinue inciting event
• Low threshold for testing
• Increase in abdominal distention, WBC > 20K or
↑Cr → call for help (ID,GI, Surg)
• Adequate delivery of vancomycin → gut via NG or rectal tube
• Subtotal colectomy may be lifesaving
Case 4
• 38 yo G 5 P 2 40+ weeks “social” induction; pushes x 2+ hrs –
LOP
• Primary C/S with 2 L blood loss, broad ligament hematoma
• Home on POD #4 feeling “ok”
• On POD #16, has fever to 104 and abdominal pain, admitted with endometritis and frank pus from vagina
• BP: 100/50 P: 100 T: 102°
WBC :15.4 PLT:405
• Broad spectrum abx x 2 days then CT scan & MRI
Pregnant and Septic? A practical approach to diagnosis and treatment
Laura Riley, MD
Associate Professor, Obstetrics, Gynecology and Reproductive Medicine
Harvard Medical School Massachusetts General Hospital
Division of Maternal‐Fetal Medicine
October 10, 2013
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Is there a role for prevention?
Preoperative management
• Showering with antiseptic agent prior to surgery
• Avoid shaving prior to surgery (clip)
• Abstain from smoking at least 30 days prior • Optimal glycemic control
• Consider decolonization for MRSA positive pts
Antimicrobial Prophylaxis
• Single dose therapy to cover Gram positive and negative organisms 60 minutes prior to skin incision (1‐
2 grams cefazolin or 1‐2 grams cefotetan IV)
• Surgery > 4 hrs duration or excess blood loss‐repeat prophylactic dose
• Morbid obesity : increase the prophylactic dose
• PCN allergy: Clinda 600mg IV and Gent 1.5 mg/kg OR Clinda 900mg and Gent 1.7mg/kg
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Case 5
• 26 yo G 3 P 1 at 19 weeks with twins and SROM of twin A
• Counseled re: risks/benefits of continuing pregnancy; pt declined termination
• Followed as outpatient x 10 days when called w/ T 100.3°
• On arrival, BP 92/44 P 96 T 102° – Sick‐appearing, uterus tender, cx long and closed, A/G/C started, post delivery 8 hrs later‐ DIC & septic shock: E.coli
In summary:
• Consider sepsis if 2 or more of following:
• Systolic BP < 90
• Mean arterial pressure < 65
• HR > 110
• WBC > 12,000 or < 4,000 or bands > 10%
• Temp > 38 ⁰Cor<36⁰C
• Sepsis bundles (lactate level, cultures, abx, fluids)
• Guidelines for ICU transfer
• Massive transfusion protocol readily available
• Ready access to consultants ( MFM, ICU, Infectious disease, Gyn Onc, Gen surgery, NICU)
References
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Angus D, van der Poll, T, Severe Sepsis and Septic Shock. N Engl J Med 2013;369:840‐51.
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Snyder C, Barton J, Severe sepsis and septic shock in pregnancy: indications for delivery and maternal and perinatal outcomes. The Journal of Maternal‐Fetal and Neonatal Medicine 2013;26(5):503‐506.
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MacFie J, Surgical sepsis. British Journal of Surgery 2013;100(S6): S36‐S39
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Barton J, Baha M, Severe sepsis and septic shock in pregnancy. Obstet Gynecol 2012;120:689–706.
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Royal College of Obstetricians and Gynecologists. Bacterial Sepsis in Pregnancy. Green‐top Guidelines No. 64A. 1st edition. April 2012.
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