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Volume 17 - No 2 - May 2013
Netherlands Journal of Critical Care
Bi-monthly journal of the Dutch Society of Intensive Care
Review
Case report
Clinical image
Current status of procalcitonin in the ICU
M. Meisner
Collapse due to acute aspiration of
a foreign body
H.F. de Kruif, G. Innemee, A. Giezeman,
A.M.E. Spoelstra-de Man
A traumatic aneurysm of the
pericallosal artery
A.C. van Dijk, W-J. van Rooij, A.M.F. Rutten
Cancidas
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• Invasieve aspergillose*
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Antifungale therapie zonder compromis
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Voor neutropenen én niet-neutropenen
Goed verdragen1
Eenvoudige dosering
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* Invasieve aspergillose bij volwassene patienten en kinderen die niet reageren op amfotericine B, toedieningsvormen van amfotericine B met lipiden en/of itraconazol of deze niet verdragen.
1. D.W. Denning: Echinocandin antifungal drugs. The Lancet 362: 1142-51, 2003. 2. Bijlage 5 Beleidsregel BR/CU-2076
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Evidence. Experience. Confidence.
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Netherlands Journal of Critical Care
Netherlands Journal of Critical Care
E x e c u ti v e e dit o ri a l b o a rd
A.B.J. Groeneveld, editor in chief
Mw. drs. I. van Stijn, managing editor
J. Box, language editor
COPYR IGH T
Netherlands Journal of Critical Care
ISSN: 1569-3511
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inhoud
ED I TO R IAL
3
A.B. Johan Groeneveld
R EV I E W S
4
Current status of procalcitonin in the ICU
M. Meisner
13
Acute viral lower respiratory tract infections in paediatric intensive
care patients
S.T.H. Bontemps, J.B. van Woensel, A.P. Bos
D e ri v ati v e w o r k s
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C A SE R E P O R T S
19
Sepsis and bleeding in an obstetric patient who is a Jehovah’s Witness
A case report with a brief review of the literature of severe septic shock
during pregnancy
V.C. van Dam, B.L. ten Tusscher, A.R.J. Girbes
23
Collapse due to acute aspiration of a foreign body
H.F. de Kruif, G. Innemee, A. Giezeman, A.M.E. Spoelstra-de Man
S u b scripti o n s
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PR O - CON
27
Non Invasive Ventilation; PROs and CONs
A.F. van der Sluijs
CL I N I C AL I MAG E
30
A traumatic aneurysm of the pericallosal artery
A.C. van Dijk, W-J. van Rooij, A.M.F. Rutten
32
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N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
1
Netherlands Journal of Critical Care
E D I T O R I AL
From February 2013 onwards, the Netherlands Journal of Critical Care (NJCC) will be published by
Van Zuiden Communications B.V. The journal will have a slightly different cover and layout. The
editorial board is grateful for this opportunity to change publishers, put forward by the Dutch Society
of Intensive Care, and hopes that it will represent a step forward in the professional growth of the
journal. Obviously, we would like to express our gratitude towards Interactie BV and the managing
editor Arthur van Zanten for their diligent help over the past ten years or so to raise the journal to
international standards. The future is not without challenges, including the shaping of the website
and online submission system and balancing the costs of publishing. While the transition may have
resulted in some delays in handling manuscripts, the editorial staff is now fully prepared to receive
and rapidly process interesting national and international papers. We welcome all high quality
submissions.
This issue of the NJCC timely highlights important ICU issues such as ICU detection of severe
infection by biomarkers and how they fit in antibiotic stewardship programmes. Life-threatening viral
infections increasingly occur and necessitate mechanical ventilation in the ICU. In this respect, we
can learn from our pediatrician colleagues how to handle these infections. And maybe non-invasive
ventilation is not always appropriate after all. We have interesting case reports and a clinical image
with unique findings.
Prof. dr. A.B. Johan Groeneveld
Editor in chief
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
3
Netherlands Journal of Critical Care
Accepted April 2013
R EV I E W
Current status of procalcitonin in the ICU
M. Meisner
Clinic of Anaesthesology and Intensive Care Medicine, Staedtisches Krankenhaus Dresden-Neustadt, Germany
Correspondence
M. Meisner – e-mail: [email protected]
Keywords - Sepsis, severe sepsis, procalcitonin, pneumonia, bacterial infections, mycoses
Abstract
This review outlines the main indications for the measurement
of procalcitonin (PCT) on the intensive care unit (ICU):
diagnosis or exclusion of sepsis (severe sepsis, septic shock) and
assessment of severity and course of sepsis-related systemic
inflammation, control of focus and response to antibiotic
therapy. Follow up measurements of PCT are frequently done
on the ICU and recommended to individualize decisions
regarding the indication and duration of antibiotic therapy.
Studies related to this topic and also the practical experience
with the routine use of this marker as a guide to treatment are
summarized in this review. Furthermore, conditions, which
may increase PCT independently from sepsis, are prevalent in
ICU patients and will also be discussed.
Use of PCT as a sepsis marker on the ICU
PCT has been recognized as a marker of sepsis since 1993.1
Initially, PCT was mainly used for the diagnosis of (bacterial)
sepsis and for the differential diagnosis of a bacterial versus
non-bacterial aetiology of systemic inflammation. In the
meantime, indications have been extended to a more dynamic
use, e.g. to follow up and guide sepsis-related therapy, including
antibiotic treatment and focus control – both in outpatients
and ICU patients. The uniform induction during sepsis, the
correlation of concentrations with severity of inflammation
(high levels in patients with severe sepsis), the relative
specificity for bacteria-induced systemic inflammation and a
short half-life of induction and elimination fitting the needs of
daily routine diagnostics support the clinical use of PCT as a
biomarker on the ICU.
Biochemistry and induction
PCT is produced by the organism and therefore an indirect
or host-response related biomarker of systemic inflammation,
mainly induced by microbial infection (sepsis, severe sepsis,
septic shock). The 114-116 amino acid protein and its shorter
calcitonin-N-ProCT fragments are measured by the presently
4
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
available diagnostic tests. The protein is induced within several
hours (3-6 hrs, peak 12-24 hours) after the respective stimulus
(e.g. endotoxinemia, sepsis, systemic inflammation and various
proinflammatory mediators). Peak levels decline with a 50%
plasma disappearance rate of roughly 1,5 days and somewhat
more in patients with severe renal dysfunction. The normal
range of PCT in healthy individuals is quite low (< 0.1 ng/
ml), so that as the reference range for diagnosis of sepsis,
concentrations above 0.25 - 0.5 ng/ml are usually used. When
deciding on antibiotic therapy, the lower threshold with higher
sensitivity is usually used. The protein has various biological
functions, e.g. chemotactic effects on monocytic cells and
modulation of expression of inducible nitric oxide synthase
(iNOS) in vascular smooth muscle cells. These functions are
partially time-dependent and they are different in native and
prestimulated cells. PCT neutralisation affects survival and
organ dysfunction in animal septic shock models. PCT can be
produced by adherent (not circulating) activated monocytes
and tissue cells, where induction is augmented by a crosstalk
of invading monocytic cells with adipocytes, as demonstrated
by ex vivo experiments.2 Also, the liver obviously plays a major
role in PCT induction. 3,4
PCT can be induced by a variety of non-septic conditions as well,
e.g., during cardiogenic shock, in patients with severe renal or
hepatic dysfunction, after major surgery, in patients with severe
systemic inflammatory response syndrome (SIRS) and multiple
organ dysfunction syndrome (MODS), as well as in severe
pancreatitis or during release of proinflammatory cytokines.4
However, as compared to severe sepsis, induction in these cases
is often moderate (usually < 2 ng/ml) and – if related to a specific
event – for a short period of time only (1-2 days). However,
conditions inducing PCT without sepsis are more frequent
in ICU patients and hence should be considered (table 1). In
addition, in patients with local infection or those with a weak
systemic inflammatory response, PCT levels may remain low. In
patients with neutropenia or those under immunosuppression
(e.g. corticosteroids) suppression of PCT is only moderate.
Netherlands Journal of Critical Care
Current status of procalcitonin in the ICU
Table 1. Conditions, which may induce PCT other than bacterial infection
Condition
Expected Peak (approx.)
Estimated range
Reference
Peak levels on day 1, rapidly declining
Postsurgical, posttraumatic
Non-abdominal trauma or surgery: low or
no PCT induction.
Abdominal or retroperitoneal surgery/
If PCT is increased above the expected typical
trauma, thoracic surgery
range, postoperative complications are more
frequently observed
< 1 ng/ml for peripheral, non-abdominal 9, 78-82
trauma or minor abdominal surgery)
< 2 ng/ml for abdominal surgery or
trauma, cardiac surgery.
2 ng/ml is possible in patients with
extended retroperitoneal or major
abdominal surgery, liver transplantation
Cardiogenic shock
May be intermediate to high (e.g.
> 0.5 ng/ml to > 10 ng/ml)
Initially no increase.
Increasing levels after 1-3 days, if high dose
catecholamines are required
83-85
MODS, severe SIRS
Increasing slowly with severity
> 0.5 ng/ml - > 10 ng/ml
17, 86, 87
Pancreatitis, severe
Initially; normal PCT indicates mild or
oedematous pancreatitis.
Increasing levels related with severity, organ
dysfunction and necrosis
< 0.2 ng/ml: mild or oedematous
pancreatitis.
In patients with severe pancreatitis:
0.5 ng/ml - > 10 ng/ml
53, 54, 58, 59
Autoimmune disorders
Usually not elevated in:
Rheumatoid arthritis, chronic arthritis, systemic
sclerodermia, amyloidosis, thyreoiditis, psoriasis,
inflammatory bowel disease, systemic lupus
erythematosus.
Can be elevated in Kawasaki Syndrome,
Goodpasture´s Syndrome, Anti-neutrophil
antibody-positive vasculitis, autoimmune
hepatitis or primary sclerosing cholangitis, M. Still
In most autoimmune disorders no or
88-94
minor induction of PCT only (0.1-1 ng/ml).
Severe renal dysfunction
If decompensated or end stage disease only, or
haemodialysis.
In the lower range, 0.1-2 ng/ml, constant
elevation
27, 95-98
Severe liver dysfunction
Chronic, Child C only
In some cases increased level in patients with
acute liver failure
In chronic disease in the lower range,
0.1-2 ng/ml, constant. In acute cases
higher levels reported
99
After prolonged resuscitation
Peak day 1
In case of prolonged CPR, levels are
related with prognosis
100, 101
Some induce significant PCT levels of
> 1 ng/ml -10 ng/ml (see left column)
Heat Shock
Acute
High concentrations reported
102, 103
New-born first days of life
Peak day 1-2
Use adapted reference range
104-106
Very rare, except MCT
107
OKT-3, Anti Lymphocyte Antigens
Acute
Medium range, low if pre-treatment with 108-110
corticosteroids
End stage of tumour disease
Chronic
Low (0.5-2 ng/ml)
42
Rhabdomyolysis
Acute
May be very high
Individual reports
Follow up recommended
111-114
Paraneoplastic
Severe burns, inhalation trauma, aspiration. First days and during severe SIRS or infection
PCT and other presently used markers of sepsis
The diagnosis of sepsis and monitoring of therapy could be
improved if PCT measurements were added to the clinical
and conventional signs of sepsis.5 PCT has different properties
when compared with CRP or lactate – markers which are often
recommended for diagnosing sepsis. CRP, for example, has a
low specificity for sepsis and concentrations do not indicate the
risk and severity of sepsis well.6-8 It responds late and plasma
levels may be affected by immunosuppression. A decline of
CRP towards the normal range may take from several days up
to one week. At the acute onset of sepsis or severe sepsis, some
patients may present with a moderate increase of CRP only (e.g.
50-100 mg/l) which may not reflect the progression or severity
of the disease. Such levels can also be observed in various other
ICU patients, e.g. post-surgical. In contrast, high CRP levels
(e.g. > 300 mg/l) are also induced after major surgery, especially
major abdominal or retroperitoneal surgery in patients without
sepsis.9 Thus, it is difficult to draw therapeutic conclusions from
CRP levels on the ICU. This may lead to under recognition of
sepsis by CRP in an acute situation.
Lactate is primarily a marker of cellular and oxidative
metabolism and perfusion and hence an epiphenomen of sepsis
only. Significantly increased or high levels of lactate mainly
occur in patients with severe or progressive stages of sepsis, e.g.
if severe organ dysfunction or septic shock are already present.
To significantly affect the outcome, sepsis must be recognized
and treated early – at best prior to the onset of shock or organ
dysfunction. Furthermore, lactate does not differentiate septic
from nonseptic shock.10
Other markers like fever, leukocytes, blood sedimentation rate,
coagulation parameters, thrombocytes, acute phase proteins
and pathogen-associated molecules like endotoxin and PCR
based methods may be useful for the diagnosis of sepsis
as well. First, as an early sign of sepsis suspected by routine
diagnostics measured for other indications (like thrombocytes
and coagulation parameters) or as a supplemental marker, but
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
5
Netherlands Journal of Critical Care
most of these markers lack specificity and their ability to assess
the risk, severity and course of the disease is often poor.
Due to the distinct profile of PCT as compared to these
markers, PCT is used in a number of ICUs as a biomarker of
sepsis – along with a variety of other signs of sepsis e.g. those
from routine measurements – and is often included in the daily
routine and clinical rounds, since diagnostic and therapeutic
decisions are influenced by this marker, e.g. the assessment of
efficacy of therapeutic measures.
Indications and measurement of PCT on the ICU
Indications for PCT measurement on the ICU basically do not
differ from indications in other patients. However, different
from the emergency department, consecutive measurements
are most frequent on the ICU. This means that patients can be
monitored and any unnecessary antibiotic use can be limited.
Single or semi-quantitative measurements for differential
diagnosis are far less useful on the ICU. Indications are
summarized in table 2.
Confirmation or exclusion of the diagnosis of sepsis,
severe sepsis, septic shock
The major strength of PCT is its high positive predictive value
to rule in the diagnosis of sepsis, severe sepsis or septic shock
and its high negative predictive value (in case of normal or low
PCT plasma concentrations) to exclude a severe SIRS, mainly
due to bacterial infection (table 3). Also, the probability for
bacteraemia is significantly increased in patients with higher
PCT levels or reduced in case of normal PCT.11-13This finding
has been confirmed by various publications and it has been
Table 2. Indications for PCT-guided monitoring of treatment on the
ICU
• To confirm or exclude diagnosis of sepsis, severe sepsis, septic shock
(including differential diagnosis)
• Assessment of severity of systemic inflammation, caused by sepsis
(severe sepsis/septic shock), reflecting the risk of organ dysfunction
and mortality. The need of urgent interventions thus can be better
estimated
• Follow up of systemic inflammation after focus removal or focus
therapy, to assess efficacy of treatment
• In patients with antibiotic treatment in order to better estimate the
duration of therapy or to withhold or stop therapy, e.g. if there is no
sepsis, if the focus has been cured. For related algorithm see below.
Exclusion criteria should be obeyed.
• To determine and monitor patients, who do not need antibiotics on the
ICU, to exclude the risk of sepsis and life-threatening systemic infection
and bacterial infection. In case of persistent elevated PCT: diagnosis
and therapy should be re-evaluated.
For specific indications:
• In patient with pancreatitis: to early asses severity and infection
• To support or exclude diagnosis of bacterial infection with high or low
probability, e.g. bacterial meningitis, bacteraemia, peritonitis, sepsis
from urinary tract infection.
• If there is no response of PCT levels to antibiotic therapy: fungal
infection or other diagnosis may be present (PCT often 1-5 ng/ml)
• PCT can also be used in out-patients for indication and monitoring of
antibiotic therapy, mainly in patients with respiratory tract infections.
6
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
Table 3. PCT levels in patients with bacterial infection and various
severity of systemic involvement
Sepsis
SIRS
Median (*), range
Mean (+), SD
Severe
sepsis
Septic
shock
Reference,
number of
observations
--
2.4 ± 0.5 (+) 37 ± 16
45 ± 22
(69) n = 145
0.6 ± 2.2 (+)
6.6 ± 22.5
35 ± 68
(70) n = 337
--
1.3 ± 0.2 (+)
2.0 ± 0
8.7 ± 2.5
39 ± 5.9
(71) n = 100
< 0.5 ng/ml (*)
0.8 ng/ml
--
4.3 ng/ml
(7) n = 190
3.8 ± 6.9 (+)
1.3 ± 2.7
9.1 ± 18.2
38 ± 59
(72) n = 101
3.0 (0.7-29.5) (*)
--
19.1
(2.8-351)
16.8 (0.9-351)
„all septic
patients“
(73) n = 33
0.5 ± 0.2 (+)
(approx.)
2±2
(approx.)
18 ± 10
(approx.)
20 ± 10
(approx.)
(74) n = 101
0.38 (*) (0.16-0.93
quartiles)
3.0 (1.48-15) 5.58
(1.84-33)
13.1 (6.1-42)
(6) n = 101
0.6 (0-5.3) (*)
3.5 (0.4-6.7) 6.2
(2.2-85)
21.3 (1.2-654) (5) n = 78
implemented in guidelines and the FDA-approval in the
USA.14-16 High PCT levels are also related to a high risk of organ
dysfunction and mortality due to sepsis.17-21 However, local
bacterial infection or bacterial colonisation cannot be excluded
by PCT. Fungal infection, when complicated by systemic
inflammation, may also induce PCT. These patients frequently
have PCT levels in a medium elevated range only (1-5 ng/ml)
or they do not respond to antibiotic therapy.22 Typically these
patients have a high risk profile. Therapy should be started
early if there is suspicion. A rapid decline after antifungal
therapy has been reported.22-24
Local infection
Local bacterial infection or bacterial colonisation usually do
not induce PCT. Even in patients with acute appendicitis, acute
cholecystitis even with local peritonitis the PCT response
may be weak. This should be known and hence diagnosis or
therapy should not be excluded by a low PCT. Interestingly, a
conservative treatment of less severe appendicitis has recently
been discussed as well.25,26 On the contrary, high PCT levels in
a patient with appendicitis or local peritonitis is undoubtedly a
sign for urgent intervention.
The information of normal PCT levels on the ICU has various
consequences: for example, microbial findings may be
interpreted as local infection or bacterial colonisation only and
antibiotic treatment may not be necessary. Further, invasive or
non-invasive diagnostic or therapeutic interventions may not
be urgently needed, since the diagnosis of sepsis is unlikely and
the sepsis-related risk of organ dysfunction and mortality are
low.
PCT elevation in patients without sepsis
Moderately increased PCT levels in patients without sepsis
have been observed at various conditions. Usually, PCT levels
in these cases are not very high (< 2 ng/ml) and induction
Netherlands Journal of Critical Care
Current status of procalcitonin in the ICU
is short (1-2 days) and often related to a specific event. Such
conditions are more frequently seen on the ICU than in the
average population. The ICU physician should know this
and interpret PCT values accordingly (table 1). However,
decisions made on an increase of PCT that are not related to
sepsis should be done by exclusion. Primarily, every increase
should be interpreted first as a possible sign of sepsis, until a
follow up and further clinical examination have excluded this
diagnosis and levels can be explained otherwise. Undoubtedly,
this is a grey area, since at the acute onset of sepsis, in patients
without organ dysfunction and during early stages of sepsis or
in patients with respiratory tract infections or pneumonia even
a small increase of PCT is important for the diagnosis of sepsis
(e.g. PCT > 0.25 ng/ml).
Depending on the type of ICU, postsurgical and posttraumatic
induction of PCT can frequently be observed, mainly following
abdominal surgery or abdominal trauma. Induction may
also relate to severe SIRS and MODS, e.g., in patients with
prolonged cardiogenic shock requiring catecholamines. Then,
the initial concentration may be low, but it may increase during
the following days sometimes even to high levels (>10 ng/ml).
In patients with severe renal or liver dysfunction, a moderate,
but constantly elevated basal level can be seen and, usually,
concentrations do not exceed 1-2 ng/ml. PCT induced by heat
shock, rhabdomyolsis and some specific types of autoimmune
disorders as well (especially those where monocytic cells are
involved) and concentrations can be quite high. Endotoxinemia
or bacterial translocation may explain induction in some
patients with prolonged cardiogenic shock, abdominal trauma
or surgery, severe acute liver dysfunction or severe MODS. In
other patients, severe tissue trauma and invasion of monocytic
cells or exposure to proinflammatory cytokines may explain
induction of PCT.
Usually, follow up of measurements in relation to a specific
event (e.g. surgery, trauma), or non-responsiveness to
therapeutic interventions (e.g. in cases of severe chronic renal
or liver dysfunction) point to induction of PCT independently
of sepsis.
Severity and course assessment: inflammation
monitoring
Assessment and monitoring of the course and severity of the
SIRS is a major indication for the measurement of PCT on
the ICU. PCT levels are a mirror of the activity of SIRS in
patients with sepsis (table 2). The 50% plasma disappearance
rate of about 1,5 days for PCT as previously mentioned allows
a daily follow up for monitoring of the patient.27 Even if the
correlation with disease severity is rather a qualitative than
a quantitative one and a gold standard is missing, high PCT
levels (e.g. concentrations from 2-10 ng/ml) usually indicate
severe systemic inflammation with high probability of organ
dysfunction.
Very high peak levels (> 100 ng and even more than 1000
ng/ml) are mostly transient and last for only 1-2 days; they
are usually seen at the acute onset of inflammation only. If
immediate therapy is effective, such high concentrations may
not necessarily indicate a fatal prognosis. For example, in
patients with pyelonephritis and urosepsis, high concentrations
have often been observed, but patients most frequently have
a good prognosis, if therapy starts immediately.28 Similarly,
a significant decline most often indicates resolution of the
disease.29,30 But on the contrary, if treatment is not effective
and PCT levels remain elevated, then the mortality rate is
increased. 5,17,29,31,32
If the infection focus has been cured and the sepsis disappeared
(as confirmed by low PCT), antibiotics can often be stopped
earlier than recommended by general guidelines, which do
not consider individual responses. 33,34 If there is no decline of
the systemic inflammatory response, then re-evaluation of the
working hypothesis or therapy is recommended.
Antibiotic stewardship: PCT- guided antibiotic therapy
Increasing evidence has been compiled that PCT can be used
to guide antibiotic therapy, leading to individualized or shorter
antibiotic treatment courses as compared to a fixed standard
regimen, also in patients on the ICU. On average, a 2-3 day
reduction of antibiotic therapy has been reported (table 4).
Most of the patients in these studies had acute respiratory tract
infections, although this approach has been used for other
infections and patients with sepsis and severe sepsis as well.
Various, albeit basically similar, algorithms have been used.
Some include both a fixed cut-off value and evaluation of the
kinetics. No negative side effects have been reported so far, but
there is on-going criticism that the statistical power to rule out
significant effects on mortality is low and that mainly patients
with lower respiratory tract infections have been investigated. 35
So far, 3691 patients have been investigated in randomized
clinical trials, of whom 166 died in control groups and 159 in
PCT-guided groups, confirming non-inferiority of the latter
strategy by excluding an effect on mortality below 8-10%. 35
With a computer based model and analysis of retrospective
ICU data from 1312 patients, a virtual use of the PCT-guided
algorithm resulted in substantial reduction of treatment costs,
based on the German diagnosis-related groups calculation. 36
In the Netherlands, a prospective study using a PCT-guided
algorithm for the management of antibiotic therapy is
underway. 37
Effects on microbial resistance rate have also been postulated,
but this has not been confirmed yet. Usually, less antibiotic
treatment is related with less microbial resistance and less
antibiotic-related side effects. Thus, the beneficial effect of this
approach may surpass the reduction of antibiotic consumption.
All patients receiving antibiotics on the ICU should be
evaluated daily by PCT. We nevertheless recommend that
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
7
Netherlands Journal of Critical Care
Table 4. Randomized controlled trials using PCT-guided algorithms to guide antibiotic therapy report a shorter and patient-adapted, individualized
antibiotic treatment
Patients included
PCT Algorithm
Result
Reference
Community acquired
pneumonia
(CAP)
PCT <0.1 ng/ml: Severe bacterial infection unlikely, prescription of
antibiotics not recommended (strong recommendation)
PCT 0.1-0.25 ng/ml: Bacterial infection requiring therapy is not
likely: antibiotic therapy is not recommended
PCT 0.25-0.5 ng/ml: Bacterial infection requiring therapy may be
present: antibiotic therapy recommended
PCT >0,5 ng/ml: Bacterial infection requiring therapy is likely:
antibiotic therapy is recommended (strong recommendation)
For patients already taking antibiotics upon
admission: if PCT <0.25 ng/ml: discontinuation
of antibiotics recommended.
Shorter duration of treatment
in the PCT group:
5 days vs. 12 days (median
of study/control group)
(33)
n = 302
Shorter duration of
Antibiotic treatment:
6 days vs. 9.5 days
(median of study/control
group)
(75)
n = 79
Shorter duration of antibiotic
Treatment in the PCT group (5.9 ± 1.7 vs.
7.9 ± 0.5 days)
Shorter duration of intensive care
Treatment in the PCT
Group
(76)
n = 110
Patients with severe sepsis Discontinuation of antibiotic therapy if regression
of clinical signs of infection and PCT
≤ 1 ng/ml or (if PCT >1 ng/ml) if decrease after
3 days to 25-35% of the baseline value.
Reduction of treatment
1.7 days in the
PCT group (6.6 ± 1.1 vs. 8.3 ± 0.7 days)
(77)
n = 27
Patients in intensive care For algorithm, see figure 1.
with suspected infections,
multicentre study
Antibiotic-free days:
PCT: 14.3 ± 9.0 days, control: 11.6 ± 8.2
days (23% relative reduction in antibiotic
exposure), no difference
In mortality (28 days)
(34)
n = 621
Antibiotic-free days:
13 days (PCT) vs. 9.5 days (control group),
27% relative reduction in antibiotic
treatment (study primary
end point). Secondary end points (risk
assessment):
no differences between the
groups (mortality, treatment
days with ventilation
or in intensive care)
(65)
n = 101
Severe sepsis, septic shock For an initial or „peak“ value of ≥ 1 ng/ml:
Follow up on day 5. End of antibiotic treatment if PCT
< 10% of the initial value or absolute value
< 0.25 ng/ml
For an initial/peak value <1 ng/ml: check on day 3: End of antibiotic
treatment if PCT < 0.1 ng/ml. If blood culture Positive: Treatment at
least 5 days.
Patients in operative
Intensive care with
sepsis (at least 2
SIRS criteria =
Severe sepsis, septic
shock)
Ventilator-associated
Pneumonia
(VAP), 5 centres
Discontinuation of antibiotic therapy after
Reduction in clinical signs of infection and PCT
≤ 1 ng/ml or – if initial value >1 ng/ml – if reduction
after 3 days to 25-35% of the starting level
(equivalent to an decrease of more than 65-75% in 3 days)
PCT after 72 hours: < 0.25 ng/ml or PCT
>0.25 ng/ml to <0.5 ng/ml or more than 80%
decrease compared with day 0: discontinuation
of antibiotic therapy is recommended (strong
or less strong recommendation, respectively).
PCT 0.5 ng/ml or less than 80% decrease or
PCT >1 ng/ml: discontinuation of antibiotic
therapy is not recommended (level of recommendation,
less strong or strong, respectively).
Daily re-evaluation after 72 hours.
further information is documented and included into decision
making on treatment. This includes clinical data regarding the
success of treatment of the infection focus and related data
(physical, biochemical and clinical signs and symptoms). Also,
the general situation of the patient should be taken into account,
as for example the presence or absence of organ dysfunction
and sepsis. The expertise of the treating subspecialty (e.g.
abdominal surgery) should also be taken into account. The
decision to stop, change or continue antibiotics should thus be
done by the medical team in a consensus decision.
In our ICU we use a checklist with documentation of
both PCT, microbiological data and a selection of further
focus-related and clinical data to increase patient safety. All
decisions are discussed with the medical team and the decision
is documented. PCT-guided recommendations are based
on the algorithm of Bouadma ( figure 1). 34 In the checklist,
8
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
source, signs and symptoms of infection and successful or
unsuccessful treatment of the focus, the presence or absence
of sepsis and organ dysfunction, PCT values and the algorithm
based recommendation and possible exclusion criteria are
documented. All criteria are re-evaluated daily with regard to
three main issues. (i) Efficacy at the onset of therapy (on day
1-3 of antibiotic treatment). If there is a response to therapy,
antibiotics are continued. (ii) After day 3, latest on day 7: the
recommendation to stop therapy (if there is no sepsis and
no acute organ dysfunction anymore and the focus has been
eliminated and PCT is low according to the algorithm). Most
frequently this is possible between days 3-6 after onset of
therapy. (iii) Re-evaluation of therapy, if treatment has not
been effective according to these criteria. Lastly, on day 7 we
suggest a final stop and basic revaluation of antibiotic therapy.
If antibiotics are continued then the reasons must be discussed
Netherlands Journal of Critical Care
Current status of procalcitonin in the ICU
Figure 1. Example of an algorithm for an individual guide for anti­biotic therapy according to ref. 34
Guidelines for initiating antibiotiocs according to PCT value.
Except any situation requiring immediate therapy …
PCT…
< 0.25 ng/ml
0.25 - 0.5 ng/ml
0.5 - < 1.0 ng/ml
≥ 1.0 ng/ml
Antibiotics strongly discouraged
Antibiotics discouraged
Antibiotics encouraged
Antibiotics strongly encouraged
Guidelines for stopping, continuing or changing antibiotics according to daily measured PCT value.
PCT …
< 0.25 ng/ml
Decline more than 80% or 80% of peak
Decline of PCT less than 80% of
(maximum) value or ≥ 0.25 to < 0.5 ng/ml peak value and PCT ≥ 0.5 ng/ml
Increase of PCT above previous and
PCT ≥ 0.5 ng/ml
Stopping antibiotics strongly
discouraged
Stopping antibiotics encouraged
Changing antibiotics strongly
encouraged
and documented. Exclusion criteria for this approach must be
known (e.g. therapy for local infection, when necessary, e.g. in
case of local destructive infection like endocarditis, infection
of cerebral drainage, bone or cartilage, impaired immunologic
function e.g. in patients with severe SIRS or MODS or infection
with specific and aggressive pathogens like tuberculosis and
other potentially harmful microbial species). Using team-based
decisions combined with clinical evaluation of the patient
rather than the PCT-based algorithm alone, we did not observe
significantly negative side effects in individual patients despite
a significant number of patients not treated by antibiotics in
our ICU.
Specific indications
Bacteraemia
On average, in patients with bacteraemia, often higher PCT
levels have been reported as compared to patients with negative
blood cultures. Also the negative predictive value of low PCT
levels to exclude bacteraemia is high.11,12,38-42 If PCT had been
used as a single decision tool, as reported in a group of patients
with urosepsis, for example, 40% fewer blood cultures would
have been taken, whereas 94-99% of patients with bacteraemia
would still be correctly diagnosed (with PCT >0.25 ng/ml).13
However, some patients with positive blood cultures may have
low or normal PCT values as well, since PCT is a marker of the
individual immune response to infection which may be weak
even during bacteraemia.
Meningitis
In patients with acute bacterial meningitis, various studies
have reported high PCT levels, most often higher than 0.5 ng/
ml. In patients with viral meningitis, PCT levels were found
to be barely elevated.43-46 This information was used to reduce
antibiotic treatment during epidemic outbreaks.47-48 Although
the initial antibiotic therapy was given to all patients (since
there may be false negative results), duration of therapy could
be significantly reduced using serial measurements of PCT. In
patients with sub acute or local infection, e.g. infection of an
Continuing antibiotics encouraged
internal or external ventricular drainage, PCT levels do not
respond sufficiently.49 Infection monitoring of patients with
ventricular drainage by PCT is thus not recommended. Also,
measurement of PCT in the cerebral fluid is not indicative.
Endocarditis
In patients with bacterial endocarditis, PCT levels are usually
elevated. Median values on admission were 3.5 ng/ml in a study
from Kocazeybek et al. (50 patients) 50 and 6.5 ng/ml in another
study by Mueller et al.51 However, similarly as in patients
with bacteraemia, PCT may be low in patients with bacterial
endocarditis, e.g. if the systemic inflammatory response is not
activated.52 Hence, echocardiography is still the gold standard.
However, also on the ICU, patients with elevated PCT levels
may have endocarditis and this focus should also be excluded
in cases of increased PCT. In our ICU, we have several case
reports of patients, primarily presenting with unspecific
symptoms, cardiogenic shock or fever but with increased PCT,
where endocarditis was diagnosed early following an elevated
PCT.
Pancreatitis
PCT may indicate severity of acute pancreatitis: if initial PCT
levels are low (< 0.2 ng/ml) this is more frequently due to
oedematous or mild pancreatitis only. 53-56 Whether antibiotic
therapy is required in these patients has not yet finally been
decided upon, but it may not be necessary if there is no
sepsis and PCT is low. During the course of the disease, high
PCT levels are more frequently seen in patients with severe
pancreatitis and infected necrosis.57-59 To assess severity,
PCT seems to be equivalent to various scoring systems.60
Discriminating infected versus non-infected necrosis, however,
is not possible by PCT levels, since severe pancreatitis also
induces PCT.61,62
Pneumonia
In patients with pneumonia, increased PCT levels may be
expected as well, but plasma levels may not be very high in all
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
9
Netherlands Journal of Critical Care
patients. Even in patients with bacterial pneumonia, depending
on the patients analysed, in up to one third of patients with
bacterial pneumonia, PCT in the lower range has been
reported, whereas in approximately another third PCT was
high. Normal or low PCT values were also reported in patients
with viral or atypical pneumonia. Nevertheless, measurement
of PCT in patients with pneumonia is recommended – not as a
primary diagnostic tool, but to follow up and assess efficacy of
treatment, both in patients with community-acquired (CAP)
and ventilator-associated pneumonia (VAP). Various studies
indicate that declining PCT levels in patients with pneumonia
indicate a favourable prognosis, whereas persistently elevated
PCT levels were more frequently observed in patients with
a fatal course.29,63 In other studies, the duration of antibiotic
treatment in patients with CAP and VAP was shorter when
PCT-guided-algorithms were used instead of fixed treatment
courses. 33,34,64,65 An individual approach to therapy in
patients with pneumonia is recommended, since pneumonia
is a very heterogeneous disease, with various aetiology,
associated pathogens, severity and patients’ risk profile. This
recommendation to use a PCT-guided approach is part of the
German guideline for the treatment of lower respiratory tract
infection and CAP.66 In various constellations, short treatment
courses with antibiotics are sufficient in some patients
without major risk factors and less severe disease.67,68 PCT
measurement supported these individual decisions, if specific
PCT-dependent algorithms were included in the therapeutic
approach in patients with CAP and lower respiratory tract
infections. 33,34,64
In conclusion
Daily quantitative measurement of PCT is recommended on
the ICU in all critically ill patients with a suspected diagnosis
of systemic inflammation, after focus removal and during
antibiotic therapy to monitor systemic inflammation and
success of therapy. This approach affects therapeutic and
diagnostic decisions, if plasma levels are interpreted together
with other clinical data. Further indications for measurement
of PCT in the ICU are related to specific questions, e.g., the
diagnosis of bacterial sepsis, meningitis, diagnosis of a possible
focus of infection e.g. endocarditis, assessment of the presence
and severity of systemic inflammation e.g. in patients with
pancreatitis or as an additional tool to exclude severe systemic
inflammation in patients with primary local infection or
bacterial colonisation. To guide antibiotic therapy, PCT can be
used not only in patients with lower respiratory tract infections
and CAP but also in sepsis and severe sepsis of different
aetiology on the ICU, resulting in shorter treatment courses
without harming the patient, this in accordance with currently
available evidence.
10
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
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71. Oberhoffer M, Bögel D, Meier-Hellmann A, Vogelsang H, Reinhart K.
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94. Eberhard OK, Haubitz M, Brunkhorst FM, Kliem V, Koch KM, Brunkhorst R.
Usefulness of procalcitonin for differentiation between activity of systemic
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Arthritis Rheum 1997;40:1250-1256.
72. Suprin K, Camus C, Gacoucin A, Le Tulzo Y, Levaoue S, Feuillu A, et al.
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73. Selberg O, Hecker H, Martin M, Klos A, Bautsch W, Köhl J. Discrimination of sepsis
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74. Müller B, Becker KL, Schächinger H, Rickenbacher PR, Huber PR, Zimmerli W, et
al. Calcitonin precursors are reliable markers of sepsis in a medical intensive care
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75. Nobre V, Harbarth S, Graf JD, Rohner P, Pugin J. Use of procalcitonin to shorten
antibiotic treatment duration in septic patients. Am J Respir Crit Care Med
2008;177:498-505.
95. Dahaba AA, Rehak PH, List WF. Procalcitonin and C-reactive protein plasma concentrations in nonseptic uremic patients undergoing hemodialysis. Intensive
Care Med 2003;29:579-583.
96. Steinbach G, Bölke E, Grünert A, Orth K, Störck M. Procalcitonin in patients with
acute and chronic renal insufficiency. Wien Klin Wochenschr 2004;116(24):849853.
97. Meisner M, Hüttemann E, Lohs T, Kasakov L, Reinhart K. Plasma concentrations
and clearance of procalcitonin during continuous veno-venous hemofiltration
in septic patients. Shock 2001;15:171-175.
98. Schmidt M, Burchardi C, Sitter T, Held E, Schiffl H. Procalcitonin in patients
undergoing chronic hemodialysis. Nephron 2000;84:187-188.
76. Hochreiter M, Köhler T, Schweiger AM, Keck FS, Bein B, von Spiegel T, et al.
Antibiotikatherapie bei operativen Intensivpatienten. Anaesthesist 2008;57:571577.
99. Elefsiniotis IS, Skounakis M, Vezali M, Pantazisa KD, Petrocheiloub A, Pirounakia
M, et al. Clinical significance of serum procalcitonin levels in patients with acute
or chronic liver disease. Eur J Gastroenterol Hepatol 2005;18:525-530.
77. Schroeder S, Hochreiter M, Koehler T, Schweiger AM, Bein B, Keck FS, et al.
Procalcitonin (PCT)-guided algorithm reduces length of antibiotic treatment in
surgical intensive care patients with severe sepsis: result of a prospective randomized study. Langenbecks Arch Surg 2009;394:221-226.
100. Fries M, Kunz D, Gressner AM, Roissant R, Kuhlen R. Procalcitonin serum levels
after ouf-of-hospital cardiac arrest. Resuscitation 2003;59:105-109.
78. Meisner M, Hutzler A, Tschaikowsky K, Harig F, von der Emde J. Postoperative
plasma concentration of procalcitonin and C-reactive protein in patients undergoing cardiac and thoracic surgery with and without cardiopulmonary bypass.
Cardiovasc Engin 1998;3:174-178.
79. Adamik B, Kübler-Kielb J, Golebiowska B, Gaminan A, Kübler A. Effect of sepsis
and cardiac surgery with cardiopulmonary bypass on plasma level of nitric
oxide metabolites, neopterin, and procalcitonin: correlation with mortality and
postoperative complications. Intensive Care Med 2000;26:1259-1267.
80. Arkader R, Troster EJ, Abellan DM, Lopez MR, Raiz R, Carciallo JA, et al.
Procalcitonin and C-reactive protein kinetics in postoperative pediatric cardiac
surgical patients. J Cardiothor Vasc Anaesth 2004;18:160-165.
81. Wanner GA, Keel M, Steckholzer U, Beier W, Stocker R, Ertel W. Relationship
between procalcitonin plasma levels and severity of injury, sepsis, organ failure,
and mortality in injured patients. Crit Care Med 2000;28:950-957.
82. Meisner M, Heide A, Schmidt J. Correlation of Procalcitonin and C-reactive
protein to inflammation, complications, and outcome during the intensive care
unit course of multiple-trauma patients. Crit Care. 2006;10:R1.
101. Oppert M, Reinicke A, Müller C, Barckow D, Frei U, Eckard KU. Elevations in procalcitonin but not C-reactive protein are associated with pneumonia after cardiopulmonary resuscitation. Resuscitation 2002;53:167-170.
102. Becker KL, Nylen ES, Arifi AA, Thompson KA, Snider RH, Alzeer A. Effekt of classic
heatstroke on serum procalcitonin. Crit Care Med 1997;25:1362-1365.
103.Hausfater P, Hurtado M, Pease S, Juillien G, al. e. Is procalcitonin a marker of
criticall illness in heatstroke? Intensive Care Med 2008;DOI10.2007/s00134 -0081083y.
104. Chiesa C, Panero A, Rossi N, Stegagno M, De Giusti M, Osborn JF, et al. Reliability
of procalcitonin concentrations for the diagnosis of sepsis in critically ill
neonates. Clinical Infectious Diseases 1998;26:664-672.
105.Turner D, Hammerman C, Rudensky B, Schlesinger Y, Goia C, Schimmel MS.
Procalcitonin in preterm infants during the first few days of life: introducing an
age related nomogram. Arch Dis Chiold Fetal Neonatal 2006;9:F283-286.
106.Stocker M, Fontana M, el Helou S, Wegscheider K, Berger TM. Effect of procalcitonin-guided decision making on duration of antibiotic therapy in suspected neonatal early-onset sepsis: prospective randomized intervention trial.
Neonatology 2010;97:165-174.
83. de Werra I, Jaccard C, Corradin SB, Chiolero R, Yersin B, Gallati H, et al. Cytokines,
nitrite/nitrate, soluble tumor necrosis factor receptors, and procalcitonin concentrations: Comparisons in patients with septic shock, cardiogenic shock, and
bacterial pneumonia. Crit Care Med 1997;25:607-613.
107. Bihan H, Becker KL, Snider RH, Nylen E, Vittaz L, Lauret C, et al. Calcitonin precursor levels in human medullary thyroid carcinoma. Thyroid 2003;13:819-822.
84. Brunkhorst FM, Forycki ZF, Wagner J. Elevated procalcitonin levels in patients
with cardiogenic shock – does bacterial inflammation influence the prognosis.
Europ Heart J 1996;17 (suppl. 2):68.
109. Sabat R, Höflich C, Döcke WD, Oppert M, Kern F, Windrich B, et al. Massive elevation of procalcitonin plasma levels in the absence of infection in kidney
transplant patients treated with pan-T-cell antibodies. Intensive Care Med
2001;27:987-991.
85. Geppert A, Steiner A, Delle-Karth G, Heinz G, Huber K. Usefulness of procalcitonin for diagnosing complicating sepsis in patients with cardiogenic shock.
Intensive Care Med 2003;29:1384-1389.
86. Whang KT, Steinwald PM, White JC, Nylen ES, Snider RH, Simon GL, et al. Serum
calcitonin precursors in sepsis and systemic inflammation. J Clin Endocrinol
Metab 1998;83:3296-3301.
87. Meisner M, Rauschmayer C, Schmidt J, Feyrer R, Cesnevar R, Bredle D, et al. Early
increase of procalcitonin after cardiovascular surgery in patients with non-infectious and infectious postoperative complications. Intensive Care Med
2002;28:1094-1102.
88. Scire CA, Cavagna L, Perotti C, Bruschi E, Caporali R, Montecucco C. Diagnostic
value of procalcitonin measurement in febrile patients with systemic autoimmune diseases. Clin Exp Rheumatol 2006;24:123-128.
89. Korczowski B. Serum procalcitonin concentration in children with liver disease.
Ped Infect Dis J 2006;25:268-269.
90. Delevaux I, Andre M, Colombier M, Albuisson E, Meylheuc F, Begue RJ, et al. Can
procalcitonin measurement help in differentiating between bacterial infection
and other kinds of inflammatory process ? Ann Rheum Dis 2003;62:337-340.
91. Scire CA, Caporali R, Perotti C, Montecucco C. Il dosaggio della procalcitonina plasmatica in reumatologia (Plasma concentration in rheumatic diseases).
Reumatismo 2003;55:113-118.
92. Kadar J, Petrovicz E. Adult-onset Still´s disease. Best Pract Res Clin Rheumatol
2004;18:663-676.
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108.Kuse ER, Jaeger K. Procalcitonin increase after anti-CD3 monoclonal antibody
therapy does not indicate infectious disease. Transpl Int 2001;14:55.
110. Abramowicz D, Schandene L, Goldmann M. Release of tumor necrosis factor,
interleukin-2, and gamma-interferon in serum after injection of OKT2 monoclonal antibody in kidney transplant recipients. Transplantation 1989;47:606-608.
111. von Heimburg D, Stieghorst W, Khorram-Sefat R, Pallua N. Procalcitonin – a
sepsis parameter in severe burn injuries. Burns 1998;24:745-750.
112. Lavrentieva A, Kontakiotis T, Lazaridis L, Tsotolis N, Koumis J, Kyriazis G, et al.
Inflammatory markers in patients with severe burn injury. What is the best indicator of sepsis? Burns 2006;33:189-194.
113.Ulrich D, Noah EM, Pallua N. Plasma-Endotoxin, Procalcitonin, C-reaktives
Protein und Organfunktionen bei Patienten mit schweren Brandverletzungen.
Handchir Mikrochir Plast Chir 2001;33:262-266.
114. Carsin H, Assicot M, Feger F, Roy O, Pennacino I, Le Bever H, et al. Evolution and
significance of circulating procalcitonin levels compared with IL-6, TNFa and
endotoxin levels early after thermal injury. Burns 1997;23:218-224.
Netherlands Journal of Critical Care
Accepted April 2013
R EV I E W
Acute viral lower respiratory tract infections in paediatric
intensive care patients
S.T.H. Bontemps, J.B. van Woensel, A.P. Bos
Emma Children’s Hospital/Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
Correspondence
S.T.H. Bontemps – e-mail: [email protected]
Keywords - Lower respiratory tract infection, children, paediatric intensive care unit, virus
Abstract
Acute lower respiratory tract infection (LRTI) is common in
children and in up to 15% of hospitalized cases subsequent
referral to a paediatric intensive care unit is necessary.
Respiratory syncytial virus, parainfluenza viruses, rhinoviruses
and newly emerging viruses like human metapneumovirus,
human bocavirus and coronaviruses are commonly isolated
pathogens from these patients. Developmental aspects of
respiratory anatomy and mechanics are of great importance
in the pathophysiology of LRTI and explain why children with
the condition are more susceptible to respiratory insufficiency
compared to adults. Studies on histopathological changes
in viral LRTI have identified both direct viral induced
cellular damage and immunopathology as playing roles in
the development of severe respiratory distress. Molecular
diagnostic tools, most importantly real time polymerase chain
reaction, have shown that mixed viral infections are common.
Clinical relevance is, however, uncertain. Host factors like
age, co-morbidity and possibly genetic factors are probably
more important in modulating disease severity. Treatment
is limited to supportive measures. Consensus regarding the
optimal mode of invasive ventilatory support is lacking. A shift
from invasive ventilatory support to non-invasive ventilation
is occurring. Ribavirin, corticosteroids, immunoglobulines
and bronchodilators are ineffective in treating viral LRTI.
Antibiotics are prescribed commonly, but their effect has not
been demonstrated in prospective randomised trials and a
bacterial pathogen is only found in half the cases. Surfactant
and small interfering RNAs may be promising treatment
options in the future. Prospective studies however are needed
to demonstrate their effect.
Introduction
Acute lower respiratory tract infection (LRTI) is common in
children and is associated with high morbidity and mortality.
Pneumonia and bronchiolitis are the most common clinical
syndromes of acute LRTI in children, however, specific
definitions are lacking. In particular, in infants and young
children signs and symptoms of pneumonia and bronchiolitis
overlap to a great extent. Therefore, many studies use the
term acute lower respiratory tract infection, making no
differentiation between pneumonia and bronchiolitis. LRTI in
infants and children may be severe and necessitate admission
to a paediatric intensive care unit (PICU). This paper will
give an up-to-date review on epidemiology, pathophysiology
and treatment options of acute life-threatening viral LRTI in
children. The aim is to provide health care workers who are less
familiar with treating severely ill children with more insight
into this condition.
Epidemiology
LRTI accounts for about 20% of all paediatric hospitalizations
in the US; of them up to 15% are admitted to a PICU.1 LRTI
is one of the most frequent reasons for mechanical ventilator
support in the PICU. In children under the age of 1 year, viral
bronchiolitis is the predominant cause (44%), after the first year
pneumonia becomes more important (25%).2 In the first year of
life, hospital admission due to LRTI is predominantly caused
by viral bronchiolitis. Hospital admittance rates for viral
bronchiolitis are approximately 20-30 per 1000 for children
younger than 1 year in the US and Europe.3 Up to 10% of these
patients may need PICU admission for supportive treatment
and monitoring.4
Causative agents
In up to two-thirds children aged 6 months to 15 years, LRTI
is caused by a virus.5 At least 26 different viruses have been
described with respiratory syncytial virus (RSV), parainfluenza
viruses and rhinoviruses as the most common agents. 5 In
children under the age of 1 month, adenovirus (10%) and
herpes simplex virus (5.5%) are also important pathogens. In
addition, adenoviruses may also lead to severe, life-threatening
pneumonia in both older children and adults.6,7 Especially
serotypes 3, 7, and 14 are capable of inducing severe necrotising
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
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Netherlands Journal of Critical Care
pneumonia.8 Among the more recently discovered viruses,
human metapneumovirus (2001), human bocavirus (2005)
and coronaviruses are recognised as a frequent cause of LRTI
in children.5,8,9 Finally, influenza A or B viruses mainly cause
pneumonia in children under 2 years of age. The importance
of viruses as a cause of life-threatening LRTI was emphasised
by the emergence of severe acute respiratory syndrome (SARS)
in 2002, avian Influenza A (H5N1) in 2003 and pandemic
Influenza A (H1N1) in 2009.
Differences between children and adults
Several developmental factors contribute to the relatively high
susceptibility of infants for developing respiratory insufficiency
over the course of a LRTI.
In the first place, developmental aspects leading to differences
in pulmonary anatomy are of interest. Children have fewer
alveoli and far less alveolar surface area compared to adults.
The number of alveoli grows from 20 million at birth to 300
million at the age of 8 years. Simultaneously, alveolar surface
area increases from 2.8 m2 to 32 m2. In adulthood alveolar
surface comprises 75 m2. Collateral ventilation channels are
not developed in the first years of life, allowing no ventilation
distal to an obstructed airway. Interalveolar channels (pores
of Krohn) appear at 1 to 2 years of age and bronchiolealveolar channels (canals of Lambert) at 6 years. Therefore,
young children are more at risk of developing atelectasis and
consequently ventilation-perfusion mismatch.
Secondly, lung mechanics are different in children. Children
have reduced elastic recoil of their alveoli. More importantly
the chest wall of an infant is more compliant and the ribs are
aligned more horizontally compared to adults. This hampers
the generation of negative intra-pleural pressure in cases of
imminent respiratory distress. In contrast to the chest wall
compliance, lung compliance is reduced in infants, leading
to a greater tendency of the lung to collapse in the setting of
respiratory disease.
Thirdly, children have significantly narrower airways compared
to adults. Considering Poiseuille’s law, we can imagine how
resistance to airflow can rise dramatically with only a minor
decrease in diameter.
Fourthly, because of relatively weak cartilaginous support
of the airways, forced expiration and subsequent rise in
intra-pleural pressure may easily cause dynamic compression
and airway obstruction. Finally, infants are more at risk of
serious respiratory infections compared to adults because
their immune system is still immature. As the child grows so
the lungs mature. Compliance of the lungs increases by 150%
during the first year of life and after the age of 6 years lung
recoil increases as well. Progressive ossification of the rib cage
and growing intercostal muscle tone decrease the compliance
of the chest wall. By the age of 10 years the ribs are oriented
downward.
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Pathology and pathophysiology
Several biological processes occur during viral infection of
the lung. Viuff et al. found widespread apoptosis in respiratory
epithelial cells in bovine RSV infected calves.10 In addition, a
marked neutrophil infiltration was noted contributing to the
obstruction of airways and alveolar filling. These findings
suggest the importance of both direct viral induced cellular
damage, mainly by apoptosis, as well as immunopathology
in the development of severe respiratory distress during viral
LRTI.10-12 Apoptosis and inflammation are probably important
mechanisms in the clearance of viral pathogens but when out of
balance may also lead to bystander injury and as such contribute
to the injurious effects in the lung. It has been shown that severe
clinical signs and pathological changes continue even after
clearance of the virus.10 The abundant neutrophil influx as seen
during RSV LRTI probably plays a key role in the development
of acute respiratory distress syndrome (ARDS) in many
children with severe RSV. A characteristic feature of RSV LRTI
is the obstruction of small airways and air-trapping by plugs of
mucus, fibrin and debris of leucocytes and dead epithelial cells.
Because children have small airways, this can already cause
hypoventilation. Obstruction is further aggravated by oedema
and peribronchiolar cellular infiltrates. Severe progressing
disease with subsequent alveolar and interstitial involvement
is characterised by infection and cell death of alveolar epithelial
cells and alveolar filling. Inflammatory infiltrates and oedema
of alveoli and interstitial tissues cause severe difficulties in gas
exchange and may present clinically as ARDS.11,13
Clinical patterns
Both pneumonia and bronchiolitis can cause severe respiratory
distress. Bronchiolitis occurs mainly in young children under the
age of 1 year and is associated with widespread crackles, wheezing
and hyperinflation.3 Pneumonia may also occur in older children
and may be associated with consolidation, infiltration or pleural
effusion.14 Initial signs of LRTI usually include cough, fever and
poor feeding. Because of the compliant chest wall and reduced
lung compliance, the work involved in breathing is higher in
children compared with adults. Clinically this presents as
marked tachypnoea, intercostal retractions, nasal flaring and
the use of respiratory accessory muscles. Obstructed narrow
airways may cause hyperinflation, wheezing and a prolonged
expiratory phase. Some infants will stop breathing from fatigue
when facing excessive respiratory demands. RSV is also able to
cause significant apnoea not induced by fatigue in which altered
sensitivity of laryngeal chemoreceptors may be involved.15 Despite
the increased work of breathing, hypoxemia and hypoventilation
may develop. Atelectasis is common and may worsen hypoxemia.
Diagnostics
The aetiology of childhood LRTI is often difficult to
establish. Clinical signs and symptoms of viral and bacterial
Netherlands Journal of Critical Care
Acute viral lower respiratory tract infections in paediatric intensive care patients
LRTI highly overlap and the isolation of a causative agent
is hampered by the difficulty of collecting lung secretions
from the lower respiratory tract. However, sputum induction
through the inhalation of hypertonic saline can provide a
solution to this problem.16 Bronchoalveolar lavage (BAL) is an
invasive technique that involves endotracheal intubation or
bronchoscopy. Therefore, it is more common to obtain material
from the upper respiratory tract by nasopharyngeal washes or
swabs. It is still controversial whether or not viruses isolated
from the upper respiratory tract truly reflect the causative
agents involved in lower respiratory disease. In particular,
rhinoviruses are notorious within this context. They are found
in up to 35% of asymptomatic children and remain detectable
for five weeks after infection.17,18
Molecular Diagnostic Tools
Traditionally used methods for detecting respiratory
viruses include viral culture, immunofluorescense assays
and measuring antibodies in paired serum samples. Viral
culture is unfit for guiding initial management strategy since
it takes days to weeks before the results are known. More
importantly, detecting viruses through cultures is not possible
for all viruses.19 Immunofluorescense assays improve patient
outcome by shortening hospitalization and reducing antibiotic
use.20 Furthermore, an important financial benefit has been
noted.20,21 Real time polymerase chain reaction (PCR) has
proved to surpass other methods for diagnosing viral LRTI.
Besides its ability to present results readily, it is possible
to detect a much broader range of viral pathogens with this
technique.1,19,22-24 Multiplex PCR assays are very sensitive and
specific. Potential benefits lie in the prevention of nosocomial
infections, reduction of diagnostic procedures and possibly
antibiotic use.21
The antibiotic controversy
Differentiating between viral, bacterial or mixed infections
on clinical grounds is not usually possible and bacterial
co-infection is not uncommon in viral LRTI.25-28 Furthermore,
some patients are suspected of concomitant sepsis. For these
reasons the majority (55-95%) of children admitted to the
PICU with viral LRTI are still treated with antibiotics. This
poses considerable overtreatment because a bacterial pathogen
is only isolated in 18-57% of cases.26-28 A number of studies,
performed in an emergency department or paediatric ward,
found a reduction in the prescription of antibiotics if the results
of fast viral testing by PCR were available. Only one study has
been performed in a PICU setting, showing that PCR had no
impact on antibiotic use in children ventilated for LRTI.29
Physicians seem more reluctant to withhold antibiotics when
treating severely ill patients with LRTI. Clinical deterioration
may be the result of bacterial superinfection and results of
bacterial cultures are usually not available on admission. It has
been shown that mechanically ventilated patients with RSV
LRTI with a positive culture of blood or endotracheal aspirate
require prolonged ventilator support, suggesting that in some
infants bacterial superinfection contributes to the development
of respiratory failure.27,30 Unrecognised bacterial co-infection
may aggravate the clinical course, especially in patients
with underlying diseases. In contrast, it is unlikely that all
patients needing PICU admission will benefit from antibiotics.
Prospective randomized trials are needed to show whether
patients with viral LRTI admitted to the PICU benefit from
treatment with antibiotics. Performing a BAL on admission
may help in guiding antibiotic treatment, as previously shown
by Bonten et al. in adult ICU patients. 31
Mixed infections
Most children suffering from viral respiratory disease only
have mild symptoms. Determining why a small subgroup of
children will develop a severe, life-threatening syndrome
poses an intriguing scientific question. PCR has shown that
viral co-infections in paediatric LRTI occur in up to 35% of
cases.17,22,32,33 The clinical relevance of the detection of multiple
viruses, however, is uncertain and there is much controversy on
this point.19,32-35 A cumulative pathogenic effect may result in
more severe disease during co-infections. Viral load in children
with RSV and hMPV infections has indeed been associated
with disease severity. 36,37,38 Alternatively, there are reports that
rhinovirus mediates triggering of interferon stimulated genes
inducing an antiviral state, thereby protecting the child from
a severe course of disease after infection with a second virus.17
Clearly, a major role of multiple infections in the determination
of disease severity has not been demonstrated.
Host factors
Host factors are likely to be of greater importance in
determining disease severity. Well known risk groups for
severe disease include young infants under the age of 3 months,
premature infants and those with an underlying illness such
as chronic lung disease, congenital heart disease, neurological
disease or immunodeficiency. 3,11 In addition, genetic factors
may be of importance. Polymorphisms in genes encoding for
TLR4, chemokine receptors and interleukins and surfactant
proteins, all of which may modulate the inflammatory
response, have been associated with disease severity in RSV
LRTI. 39,40
Treatment
Antiviral drugs
Ribavirin has broad antiviral activity against both DNA and
RNA viruses. There has been much debate on the effectiveness
of Ribavirin in infections caused by adenovirus, human
metapneumovirus, parainfluenza virus and RSV.7,41-44 Apparent
clinical success is limited to case reports and small series and
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as far as we know there have been no prospective randomized
controlled trials.45 Ribavirin is therefore not recommended.
Varicella-Zoster or Herpes Simplex LRTI may be treated with
Aciclovir. Influenza A and B infections can be treated with
neuraminidase inhibitors such as Oseltamivir and Zanamivir.
If started within 48 hours after the onset of symptoms, they
reduce median time to resolution of symptoms by 0.5-2.5
days.46 According to WHO guidelines, Oseltamivir is also
the drug of choice in the treatment of pandemic influenza A
(H1N1) and avian influenza (H5N1).47,48
Antibiotics
The British Thoracic Society (BTS) advises considering treating
every child with severe LRTI with antibiotics since bacterial
and viral LRTI cannot be reliably distinguished from each
other.49 Randomised controlled trials evaluating the effect of
antibiotics in mild to moderate RSV LRTI, have shown that
antibiotics are not beneficial. 50 However, no such data for
children admitted to a PICU are available. Consequently,
a reduction in antibiotic use is unlikely until prospective
trials have shown whether these patients will benefit from
antibiotics. Performing a BAL on admission may be helpful in
guiding antibiotic treatment.
Corticosteroids and Intravenous immunoglobulines
Besides cytopathic effects on respiratory epithelial cells, the
host cellular immune response contributes to the pathogenesis
of RSV LRTI. Therefore, patients may benefit from treatment
with immunosuppressive drugs such as corticosteroids or
intravenous immunoglobulin. There is abundant evidence,
however, that corticosteroids are not effective in the treatment
of RSV. In 2010 a Cochrane review found no clinical relevant
effect of systemic or inhaled glucocorticoids in the treatment of
acute viral bronchiolitis.51 Furthermore, no beneficial effect of
dexamethasone was found in children mechanically ventilated
for severe RSV LRTI.52,53 Although not based on solid scientific
data, corticosteroids are not recommended for treatment
of coronaviruses (including SARS), seasonal influenza,
pandemic H1N1 and avian influenza H5N1.7,47,48 Intravenous
immunoglobulin with a high neutralizing activity against RSV
has showed to be ineffective and should not be used.54
Surfactant
Damage to pneumocytes and alveolar filling result in reduced
synthesis and inactivation of surfactant. Depletion of surfactant
may be aggravated by damage to the alveolo-capillary
membrane and by mechanical ventilation. Exogenous
surfactant therefore, is a potentially promising intervention.
A meta-analysis on the treatment of bronchiolitis indeed
found a significant reduction in the duration of mechanical
ventilation and the length of stay in the PICU. 55 Data on the
effects of exogenous surfactant on children with severe viral
16
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LRTI are limited. Exogenous surfactant can not, therefore, be
recommended as routine treatment but may be used in severe
cases.
Bronchodilators
There is no scientific basis for routine use of b2-agonists in
viral LRTI. A recent trial could not demonstrate any significant
benefit of bronchodilator treatment with b2-agonists or
racemic epinephrine in mechanically ventilated patients with
RSV-bronchiolitis.56 In addition, a 2010 cochrane review found
no benefit of bronchodilators in the treatment of acute viral
bronchiolitis.57 b2-agonists may be administered on a trial and
error basis if lower airway obstruction is clinically apparent,
but should be discontinued if no clinical improvement is
demonstrated. There is no evidence of effectiveness for
epinephrine in the treatment of acute viral bronchiolitis in
children under 2 years of age.58 A combination of epinephrine
and dexamethasone was also shown to be ineffective.58
Ventilatory support
Ventilatory support may be lifesaving in severe viral LRTI.
However, consensus regarding the optimal mode of ventilatory
support and ventilation technique in conventional mechanical
ventilation is lacking.11 Data on high frequency oxygenation
(HFO) for viral LRTI are limited. Moreover, there are concerns
about the risk of air-trapping due to the passive expiration
phase. Although a small series described successful use
with active expiration, routine use is not recommended.59
Non-invasive ventilation (NIV) is suggested as a safe and
effective method for infants with bronchiolitis.60 Yet, evidence
to define indications and methods of NIV in children is
lacking.61 Retrospective data show that NIV reduces the rate
of ventilator associated pneumonia and is associated with a
decreased need for invasive respiratory support.62,63 NIV was
successful in 83% of cases overall and 94% if no risk factor
was present and resulted in a reduction in length of stay in the
PICU. In cases of failure of conventional ventilatory support
methods, extracorporeal membrane oxygenation may be used
as a rescue therapy.
Future therapy
A promising novel antiviral treatment strategy currently
under development is that of small interfering RNAs (siRNA).
The majority of RNA within cells is the so called non-coding
RNA. It exerts specific and profound functional control on the
regulation of protein production and controls the expression
of all genes through processes collectively known as RNA
interference. Controlling this naturally occurring regulation
of protein production has huge therapeutic potential. It
regulates gene expression through the silencing of specific
messenger RNAs. Methods are under development that allow
the degradation of targeted mRNAs with specifically designed
Netherlands Journal of Critical Care
Acute viral lower respiratory tract infections in paediatric intensive care patients
siRNAs. These have been shown to exert potent antiviral effects
against RSV, parainfluenza virus, influenza, coronaviruses,
measles and hMPV in vitro and in vivo.64 Clearly, prospective
trials are needed to demonstrate clinical benefits before routine
use can be recommended.
Conclusion
Acute viral LRTI is a major reason for mechanical ventilatory
support in the PICU. Children more than adults are at risk
of respiratory insufficiency due to differences in respiratory
anatomy and mechanics. Viral agents may cause severe lung
damage leading to severe respiratory distress, development of
ARDS and a need for mechanical ventilation. This is due to
both direct virus induced cellular damage and inflammation
of the lower respiratory tract. Mixed infections are common,
but clinical significance in determining disease severity is still
unclear. Host factors are more likely important modulators
of disease severity. A reduction of antibiotic overtreatment
is challenging, because bacterial co-infection does not add
specific symptoms to the signs already present in viral LRTI,
but may aggravate the clinical course. Therapeutic options are
mainly supportive. A shift from invasive ventilatory support
to NIV has been noted. Future research is needed to expand
current limited causative treatment options and determine the
role of antibiotics in treating severe, viral LRTI in children.
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Netherlands Journal of Critical Care
Accepted March 2013
CASE REPORT
Sepsis and bleeding in an obstetric patient who is
a Jehovah’s Witness
A case report with a brief review of the literature of severe septic shock during pregnancy
V.C. van Dam1,2, B.L. ten Tusscher1, A.R.J. Girbes1
Department of Intensive Care Medicine, VU University Medical Center Amsterdam, The Netherlands
1
2
Current address: Department of Intensive Care Medicine, Westfriesgasthuis Hoorn, The Netherlands
Correspondence
V.C. van Dam – e-mail: [email protected]
Keywords - Sepsis, obstetric patient, Jehovah’s Witness
Abstract
Sepsis in pregnancy is an important cause of maternal deaths
worldwide with the vast majority of these deaths occurring in
low-income countries. In developed countries, septic shock in
obstetric patients is relatively rare and not often a reason for
ICU admission; eclampsia, preeclampsia and major obstetric
haemorrhage are far more common reasons for ICU admission
during and after pregnancy.
Due to an altered physiological status in pregnancy, early
recognition and treatment of obstetric sepsis can be
complicated and different from non-obstetric sepsis. Early
recognition and prompt therapy is however, crucial to reduce
maternal and foetal morbidity and mortality. The main goal in
treating septic shock in pregnancy is to effectively resuscitate
the mother as this usually adequately resuscitates the foetus.
Early focused empiric antibiotic treatment should be initiated.
Sepsis in obstetric patients is primarily the result of pelvic
infections such as intra-amniotic infections, endometritis,
septic abortions, or urinary tract infections.
We discuss a case of septic shock in an obstetric patient,
highlighting the treatment of sepsis in pregnancy with an
emphasis on changed physiology. In addition, we will briefly
address the consequences of a patient refusing blood products
in this context, as our patient did being a practising Jehovah’s
Witness.
Introduction
Nowadays, maternal sepsis accounts for only a small proportion
of maternal deaths in high-income countries. In western
countries, reported incidences of severe maternal morbidity
as a result of sepsis vary from 0.1 to 0.6 per 1000 deliveries.1
Although maternal sepsis is relatively uncommon, thorough
knowledge of the development of sepsis and septic shock and
especially the altered physiology in pregnancy are essential
in treating the obstetric patient. We discuss a complex case
of septic shock in an obstetric patient in the context of the
changed physiology. In addition, we will briefly discuss the
consequences of refusing blood products in pregnant Jehovah’s
Witnesses and the risk of maternal death.
Case history
A 27-year-old gravida 3 para 0 was presented at the outpatient
clinic at 20 weeks of gestation. Her medical history included
two missed abortions for which she underwent curettage
and intra-uterine adhesiolysis. She was a practising Jehovah’s
Witness who had signed an advanced directive declining blood
transfusion in the recent past and her partner confirmed her
wishes.
At 20 weeks of gestational age, routine abdominal ultrasound
was performed and showed no structural abnormalities.
However, a transvaginal ultrasound, which was performed
within the context of scientific research, revealed shortening
of the cervix length and an open ostium internum. Speculum
examination followed, and showed protrusion of the amniotic
membranes into the cervical channel.
The patient was admitted because of the risk of premature
labour. On admission she felt well, but mentioned that she had
had discoloured vaginal discharge for 2 days. Laboratory results
showed a concentration of C-reactive protein of 30 mg/L with a
leukocyte count of 10 x 109/L. Although the patient’s symptoms
were minimal, an infection could not be excluded and she was
started on empiric intravenous amoxicillin-clavulanic acid
after blood cultures had been taken. In addition, indometacine
was prescribed in an attempt to delay delivery.
The following day, she was referred to our university hospital
for possible tertiary cerclage. Cerclage was not performed
immediately because of suspicion of infection and the risk of
rupture of the membranes. On day 2 of admission, the patient’s
temperature went up to 40 degrees Celsius and she complained
of painful contractions. Rapidly progressive hypotension and
tachycardia developed and fluid resuscitation was initiated. An
intra-amniotic infection with septic shock was suspected and it
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
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Netherlands Journal of Critical Care
was decided to terminate the pregnancy. An amniocentesis was
performed, and malodorous amniotic fluid was sent for culture.
Our patient received oxytocine and after 5 hours she gave birth
to a dead male foetus of 473 gram. The delivery was complicated
by retention of the placenta in spite of active management of
the third stage of labour for which manual removal of the
placenta was performed. Estimated total blood loss was 1500
ml. During the procedure the patient was haemodynamically
highly unstable and needed continuous fluid resuscitation
and vasopressors. In view of her confirmed Jehovah Witness
conviction, blood transfusion was not an option.
After removal of the placenta, the patient was transferred to the
intensive care unit where she deteriorated towards profound
septic shock, multi organ failure, including acute respiratory
distress syndrome (ARDS) and renal failure. Laboratory
results suggested disseminated intravascular coagulation. Her
haemoglobin levels dropped to 2.9 mmol/L and her platelet
count dropped as low as 13 x 109/L. There were no laboratory
signs of haemolysis. She was treated with ceftriaxone and a
single dose of gentamycin. In addition to vasopressors, she was
given hydrocortisone therapy at a dose of 100 mg TID i.v.
Chest X-ray showed bilateral opacities compatible with
ARDS. Transoesophageal echocardiography demonstrated a
relatively hypovolaemic left ventricle, slight diffuse myocardial
depression, but no obvious signs of cardiomyopathy. Prone
position ventilation was initiated because of refractory
hypoxaemia due to ARDS.
Shortly after admission to the ICU, blood cultures yielded
gram-negative rods and the following day Escherichia coli
was identified, which was also isolated from cultures of the
foetal nares and external auditory canal of the foetus. The
isolated E.coli was resistant to amoxicillin-clavulanic acid, but
susceptible to cephalosporines. Histopathological examination
of the placenta revealed invasion of neutrophils and bacilli into
the chorionic villi ( figure 1 and 2).
On the sixth day of admission, white blood cell count peaked
at 106 x 109/L. Our patient ultimately responded to treatment
and there were no haemorrhagic complications. Antibiotic
treatment was administered for 10 days. Multiple organ
dysfunction resolved over the following weeks. Management of
the patient also included supplemental erythropoietin therapy
and iron. She was on mechanical ventilation for 20 days and
needed renal replacement therapy until discharge from the ICU
at day 26. Renal function recovered slowly during the following
weeks and after 6 weeks she was able to come off dialysis.
Discussion
Severe maternal morbidity complicates at least 0.71% of
all pregnancies in the Netherlands. The LEMMonN study,
a Nationwide Enquiry into ethnic determinants of Severe
Maternal Morbidity in the Netherlands, reported an incidence
of admission to the ICU of 2.4 per 1000 deliveries between 2004
20
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
Figure 1. Chorionic villi heavily infiltrated by numerous neutrophils
Figure 2. Chorionic villus showing bacilli and neutrophils
and 2006.2 The most common reasons for ICU admission are
preeclampsia, eclampsia, and major obstetric haemorrhage. 3
In developed countries, septic shock in obstetric patients is
rare. Kramer et al. found an incidence of severe sepsis of 0.2
per 1000 deliveries.4 Sepsis in obstetric patients is primarily
the result of pelvic infections due to intra-amniotic infections,
endometritis, wound infections, septic abortions, or urinary
tract infections.
Intra-amniotic infection (IAI) refers to infection of the
amniotic fluid, membranes, placenta and/or decidua. Studies
indicate that IAI complicates between 0.5% and 10% of all
pregnancies.5,6 Any factor that increases the risk of prolonged
exposure of the foetal membranes to ascending microbes from
the vagina will increase the risk of IAI (e.g. preterm delivery
and number of vaginal examinations). The pathogens most
Netherlands Journal of Critical Care
Sepsis and bleeding in an obstetric patient who is a Jehovah’s Witness
frequently isolated from the amniotic fluid are Gardnerella
vaginalis, Ureaplasma urealyticum, Bacteroides bivius,
Streptococci and Escherichia coli. Approximately 5 to 10 %
of women with IAI will develop bacteraemia, but only a small
number of these patients develop septic shock. In those who do
develop sepsis, studies have shown aerobic gram-negative rods
to be the principal etiologic agents, followed by gram-positive
bacteria and mixed or fungal infections.7
Several complex physiologic adaptations occur during
pregnancy, which can mask the initial signs of sepsis and
make these patients susceptible to rapid deterioration. These
physiological changes must be taken into account when treating
the infectious obstetric patient. 8 First, in pregnant patients,
blood pressure is often decreased as a result of a decrease in
vascular resistance. Arterial pressure during pregnancy is
predominantly maintained by increased cardiac output due
to an increase in stroke volume, particularly in the first two
trimesters. As a result, maternal cardiovascular functional
residual capacity is limited and sepsis-induced myocardial
contractile dysfunction can rapidly lead to haemodynamic
collapse.9
Progesterone, produced by the placenta, has a respiratory
stimulant effect and leads to an increase in tidal volume and
a generally unchanged respiratory rate. Functional residual
capacity is decreased by 25%, and oxygen consumption
increases as a result of increased metabolic needs of the
mother and foetus. Arterial blood gas analysis typically shows
respiratory alkalosis. Although this adaptation is beneficial in
normal pregnancy, in the setting of sepsis and/or respiratory
failure, these changes predispose the patient to a rapid decline
in oxygenation and decreased ability to compensate or buffer
metabolic acidosis. 8,10
During pregnancy the plasma volume increases up to 10-15%,
albumin and protein concentrations decrease, resulting in
lower osmotic pressure, predisposing for an accumulation of
interstitial fluid. Consequently, pregnant patients are more
susceptible to pulmonary oedema.
The increased plasma volume is greater than the increase in
haemoglobin mass and erythrocyte volume. This is responsible
for a modest fall in the haemoglobin level, called dilutional
(physiological) anaemia of pregnancy.
The early recognition of the condition and subsequent prompt
treatment is crucial to reducing maternal and foetal morbidity
and mortality in women with suspected sepsis. The overall goal
in the management of pregnancy that is complicated by septic
shock is to immediately resuscitate the mother. Resuscitation
of the mother will usually adequately resuscitate the foetus.
Delivery in the setting of maternal instability increases
maternal and foetal mortality rates.11 The only obvious
exception is if the intra-uterine environment is the source
of infection, as in our case, in which prompt delivery may be
life-saving.
A pregnant hypotensive patient is best placed in a left
lateral tilt to prevent compression of the inferior vena cava
by the gravid uterus from 20 weeks pregnancy on. As in
non-pregnant patients, initial resuscitation consists of
administering crystalloids or colloids to restore and maintain
tissue perfusion. Early goal directed therapy with goals as
described by the Surviving Sepsis Campaign are already a
subject of discussion in the general population and may not be
directly applicable to pregnant patients with shock and sepsis
– as normal values during pregnancy differ from non-pregnant
patients. No studies have specifically evaluated the use of CVP
measurements in obstetrical patients with sepsis. Invasive
monitoring with a pulmonary artery catheter has been studied
in obstetric patients,12-14 but its use in gravid and non-gravid
septic patients remains undetermined.
There is no contraindication for the use of inotropes and/or
vasopressors in gravid patients and inotropic therapy may be
necessary to optimize haemodynamic status. The vasopressor
of choice for maternal hypotension is not completely clear.
Few studies have been performed in humans, but these
do not provide conclusive data, however norepinephrine
and dopamine can be used to increase maternal blood
pressure but both can decrease uterine blood flow due to the
vasoconstriction of uterine vascular beds.15,11 Frequent clinical
assessment of organ perfusion, and early foetal monitoring
(which can reflect derangements of the mother’s condition) are
essential.
The identification and prompt eradication of the source of
infection is of extreme importance in treating sepsis both
in pregnant and non-pregnant patients. A septic abortion
(although rare in the Netherlands) should be curettaged
promptly and wound infections opened and debrided.
Necrotizing fasciitis can be rapidly fatal and must be treated
aggressively. Surgical or imaging-guided percutaneous or
transvaginal drainage of the infectious focus is essential in
patients with severe intra-abdominal or pelvic infections.
In cases of an intra-amniotic infection, delivery should be
accomplished as soon as possible, regardless of gestational age.
Intravenous broad-spectrum antibiotics should be administered,
starting within 1 hour of the diagnosis of severe sepsis or septic
shock, preferably after blood cultures have been obtained. The
choice of antibiotic is based on the suspected infection site and
likely causative micro-organism. Empirical antibiotic selection
should address the safety of the drug to the foetus, especially
during the first trimester, when major organogenesis takes
place.
The prognosis of recovery from septic shock in the gravid patient
seems favourable, and the risk of death is much lower when
compared with that of a non-gravid population. This has been
attributed to a lack of associated underlying co-morbid conditions,
younger age group, and a focused site of potential infection
such as the pelvis (that may be more amenable to medical and
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
21
Netherlands Journal of Critical Care
surgical intervention).9 Still, sepsis is a life-threatening condition
for women during pregnancy, childbirth, and puerperium.4
Evidence-based guidelines may further reduce the overall risk
of mortality and morbidity from maternal sepsis. Although
approaches like the Surviving Sepsis Campaign are unproven
in the obstetric population, the basic principles of prompt
resuscitation, antibiotic treatment and source control are likely
to be applicable to all patients with sepsis.
In our case, treatment was complicated because the patient was
a practising Jehovah’s Witness and refused blood products. In
the United Kingdom, the 2003-2005 Confidential Enquiry into
Maternal and Child Heath reported haemorrhage to be the
second leading cause of direct maternal death and included
14 women who had declined blood transfusion.16 Recently, a
retrospective study in the Netherlands by Van Wolfswinkel et al.,
found that women who are Jehovah’s Witnesses, are at a six times
increased risk for maternal death and at a 130 times increased
risk for maternal death because of major obstetric haemorrhage,
compared to the general Dutch population.17 Oxygen transport
can be impaired by low haemoglobin concentrations, especially
in cases of sepsis. However, optimization of cardiac output
and oxygen tension can modulate this effect.18 Monitoring
continuous cardiac output can be useful for assessing tissue
oxygen delivery and to guide treatment in post-partum anaemia
in Jehovah’s Witnesses – bearing in mind the described altered
physical changes in pregnancy.19
Conclusion
We have described a complex case of an E.coli sepsis due
to an intra-uterine infection complicated by ARDS, acute
renal failure, severe anaemia and disseminated intravascular
coagulation in a patient who was a Jehovah’s Witness. Maternal
sepsis accounts for a small proportion of maternal deaths
in high-income countries. In spite of lower mortality rates
compared to non-obstetric patients with sepsis, this condition
can constitute a life-threatening situation for young expectant
women and needs prompt and effective treatment. Sepsis in
these women can be difficult to identify because of the distinct
physiological changes in pregnancy. Knowledge of these changes
is essential in order to properly interpret the hemodynamic
data and to identify the risk of rapid deterioration in septic
obstetric patients. Further, in practising Jehovah’s Witnesses,
haemorrhage should be treated sufficiently, which may include a
rapid decision to proceed to hysterectomy when indicated.
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1.
Van Dillen J, Zwart J, Schutte J, van Roosmalen J. Maternal sepsis: epidemiology,
etiology and outcome. Curr Opin Infect Dis 2010;23:249-254
2. Zwart JJ, Richters JM, de Vries JIP, Bloemenkamp KWM, van Roosmalen J.
Severe maternal morbidity during pregnancy, delivery and puerperium in the
Netherlands: a nationwide population-based study of 371 000 pregnancies.
British Journal of Obstetrics and Gynecology 2008;115:842-850
3.
Keizer JL, Zwart JJ, Meerman RH, Harinck BIJ, Feuth HDM, van Roosmalen J.
Obstetric intensive care admissions: A 12-year review in a tertiary care centre.
Eur J Obstet Gynecol and Repr Biol 2006;128:152-156
4. Kramer HMC, Schutte JM, Zwart JJ, Schuitemaker NEW, Steegers EAP, van
Roosmalen J. Maternal mortality and severe morbidity from sepsis in the
Netherlands. Acta Obstetricia et Gynecologica 2009;88:647-653
5.
Soper D, Mayhall C, Dalton H. Risk factors for intraamniotic infection: A prospective epidemiologic study. Am J Obstet Gynecol 1989;161:562-568
6. Soper D, Mayhall C, Frogatt J. Characterization and control of intraamniotic
infection in an urban teaching hospital. Am J Obstet Gynecol 1996;175:304-310
7.
Fahey OF. Clinical management of intra-amniotic infection and chorioamnionitis: A review of literature. J Midwifery Womens Health 2008;53:227-235
8.
Fujitani S, Baldisseri MR. Hemodynamic assessment in a pregnant and peripartum patient. Crit Care Med 2005;33:No.10 (Suppl.)
9.
Fernandez-Perez ER, Salman S, Pendem S, Farmer JCh. Sepsis during pregnancy.
Crit Care Med 2005;33:No.10 (Suppl.)
10. Cole DE, Taylor TL, McCullough DM, Shoff CT, Derdak SD. Acute respiratory
distress syndrome in pregnancy. Crit Care Med 2005;33:No. 10 (Suppl.)
11. Sheffield JS. Sepsis and septic shock in pregnancy. Crit Care Clin 2004;20:651660
12. Belfort MA, Mares A, Saade GR et al. Rapid echocardiographic assessment of left
and right heart hemodynamics in critically ill obstetric patients. Am J Obstet
Gynecol 1994;171:884-892
13. Gilbert WM, Towner DR, Field NT et al. The safety and utility of pulmonary artery
catheterisation in severe preeclampsia and eclampsia. Am J Obstet Gynecol
2000;182:1397-1403
14. Wallenburg HC. Invasive hemodynamic monitoring in pregnancy. Eur J Obstet
Gynecol Reprod Biol 1991;42:S45-S51 (Suppl.)
15. Guinn DA, Abel DE, Tomlinson MW. Early Goal Directed Therapy for Sepsis
During Pregnancy. Obstetrics and Gynaecology Clinics of North America
2007;34:459-479
16. Lewis G. The Confidential Enquiry into Maternal and Child Health (CEMACH).
Saving mothers’ lives: reviewing maternal deaths to make motherhood safer2003–2005. The seventh report on confidential enquiries into maternal deaths
in the United Kingdom, London: CEMACH; 2007.
17. Van Wolffswinkel ME, Zwart JJ, Schutte JM, Duvekot JJ, Pel M, van Roosmalen J.
Maternal mortality and serious maternal morbidity in Jehovah’s witnesses in the
Netherlands. BJOG 2009;116:1103-1110
18. Rasanayagam SR, Cooper GM. Two cases of severe postpartum anemia in
Jehovah’s witnesses. Int J Obstet Anesth 1996;5:202–5.
19. Piraccini E, Corso RM, Agnoletti V, Terzitta M, Valtancoli E, Gambale G. Cardiac
output and fluid replacement in a Jehovah’s Witness with severe postpartum
hemorrhage. Int J Obstet Anesth. 2010 Oct;19(4):462-3
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Netherlands Journal of Critical Care
Accepted April 2013
CASE REPORT
Collapse due to acute aspiration of a foreign body
H.F. de Kruif1, G. Innemee2, A. Giezeman2, A.M.E. Spoelstra-de Man3
Resident Emergency Medicine, Academic Medical Center, Amsterdam (AMC)
1
2
Department of Intensive Care, Tergooi Hospitals, Hilversum
3
Department of Intensive Care, VU University Medical Center, Amsterdam
Correspondence
H.F. de Kruif – e-mail: [email protected]
Keywords - Acute collapse, foreign body, aspiration, asphyxiation, cafe coronary, bronchoscopy
Abstract
An acute collapse calls for urgent and appropriate action. Yet,
it is difficult to have a comprehensive differential diagnosis in
such a situation. Foreign body aspiration is a major cause of
collapse that should be considered. Prompt diagnosis and early
focused intervention are crucial for outcome.
In the two cases described here, there was a collapse due to
foreign body aspiration. In the first case, a 56-year-old female
was found while losing consciousness. The cause of her collapse
was not immediately clear and extensive diagnostics did not
reveal the cause. After extubation the anamnesis eventually
brought clarification and yielded the diagnosis of aspiration.
In the second case, an 83-year-old female was suddenly seen
motionless in her chair. Her family told attending paramedics
that she often choked on food so that they could remove the
obstructing food remnants from the pharynx.
Collapse as presentation of a foreign body aspiration is rare.
In a complete closure of the airway, there is no possibility
for speaking or breathing and unconsciousness soon follows.
Confusion with a cardiac event, known as the cafe coronary,
frequently occurs. More commonly a partial obstruction of the
airway occurs and symptoms mostly include cough, dyspnoea,
vomiting and wheezing.
In an asphyxiating foreign body aspiration immediate actions
are vital, however, the possibility of choking in collapse is not
always considered. When suspecting a foreign body aspiration
in a case of collapse, removing the object that obstructs the
airway and re-establishing an airway has priority. The gold
standard in treating an asphyxiating foreign body aspiration is
rigid bronchoscopy.
Introduction
An acute collapse calls for urgent and appropriate action by the
clinician. However, the list of differential diagnoses is long and
it is often difficult to determine the underlying cause. Acute
foreign body aspiration is an uncommon, yet severe cause of
collapse that has to be considered. Prompt diagnosis is crucial
and early focused intervention is the key to survival. The
following cases are two examples.
Case 1
Patient A, a 56-year-old woman, collapsed in front of her
neighbour’s door. She had rang the doorbell breathless and in a
panic after which she had collapsed. On arrival the paramedics
saw a restless, cyanotic and respiratory insufficient woman with
impaired consciousness. The peripheral oxygen saturation was
72% and she was incontinent for urine. They sedated her and
after an uncomplicated endotracheal intubation transported
her to the hospital.
Upon arrival at the Emergency Department (ED) a (hetero)
anamnesis was not possible as the patient came without
relatives or neighbours. Physical examination revealed, except
for distended neck veins, no abnormalities. The patient was
easily ventilated and haemodynamically stable without
vasopressive medication (RR 130/65 mmHg and heart rate
60 bpm). The Glasgow Coma Score was E1M1Vt and she
had normal pupillary reflexes without further sedation. The
electrocardiogram (ECG) did not show ischemia and the
laboratory results were normal. A computed tomography
(CT) scan of thorax/brain and echocardiography revealed no
abnormalities. Bronchoscopy was not performed because no
abnormalities had been seen at intubation, ventilation was
unimpaired and radiologic studies showed no signs of a corpus
alienum, so aspiration was not considered a likely cause. At this
time, we did not know the cause of the acute collapse despite
extensive diagnostic testing.
In the Intensive Care Unit (ICU) the patient did not need
haemodynamic support and hardly any ventilatory support.
After discontinuation of sedation the patient awoke to a
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
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Netherlands Journal of Critical Care
maximal Glasgow Coma Score and gesticulated that she
wanted to be taken off the ventilator. “No more liquorice for
me!” were the first words of the patient immediately after
extubation. She told doctors that she had suddenly choked
on a ‘liquorice smiley’ ( figure 1). Acutely short of breath she
had run to her neighbour’s door, rang the doorbell and then
lost consciousness. Afterwards the neighbour told us that
the patient had yelled, “I’m suffocating!” After detubation the
patient never showed any symptoms of dyspnoea or stridor.
The following day the patient was transferred to the
Department of Internal Medicine and could be discharged
home shortly afterwards. A few weeks later the patient was seen
at the Internal Medicine outpatient clinic. She had no further
health complaints. The liquorice smiley was never found.
Case 2
Patient B, an 83-year-old woman, suddenly showed signs of
choking during a family dinner and then became motionless
in her chair. The family called the emergency services, but
did not start BLS (basic life support). The paramedics arrived
after seven minutes and found the patient in asystole. They
were told by the family that the patient often choked on her
food. During inspection of the mouth and pharynx by the
ambulance paramedics large obstructing food remnants were
found. These were removed with a Magill forceps ( figure 2).
After endotracheal intubation, the patient could be ventilated
without difficulty. After 4 minutes of advanced cardiac life
support (with a total 2 mg of epinephrine) the heart rate and
circulation restored. The first end tidal pCO2 measured by
capnography was 14 kPa, which soon decreased to 7 kPa with
adequate ventilation (normal: 4.7 to 6.0 kPa).
After arrival at the hospital, the patient received low ventilatory
pressures and did not need any hemodynamic support (RR
180/90 mmHg and heart rate 110 bpm). Physical examination
Figure 1. Example of liquorice smiley
Figure 2. Removed food remains from the mouth and pharynx of
patient B
Thanks to L. (Leon) Vos, paramedic RAV Gooi and Vechtstreek,
The Netherlands.
revealed no further abnormalities. Her Glasgow Coma Score
was 3 (E1M1Vt) without sedation. An ECG showed an irregular
sinus rhythm with no significant signs of ischemia and cardiac
enzymes remained negative. An echocardiography was not
performed. The chest X-ray showed a good tube position and
no signs of atelectasis. The first laboratory tests showed a severe
metabolic acidosis, probably due to prolonged circulatory
arrest: pH 6.96 (normal: 7.35 to 7.45) and lactate 9.0 mmol/l
(normal: up to 2.0 mmol/l). Her hemodynamic and respiratory
condition quickly recovered. However, despite therapeutic
hypothermia, she had a poor neurological outcome and died
two and a half weeks later.
Discussion
Collapse as presentation of a foreign body aspiration is not
common. Only in seven to ten percent of cases is an acute
foreign body aspiration associated with choking, acute severe
respiratory distress or sudden collapse.1,2 The diagnosis of
aspiration can be complicated as the presenting symptoms are
variable and can resemble other diseases.
24
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Netherlands Journal of Critical Care
Collapse due to acute aspiration of a foreign body
Epidemiology
Aspiration among adults is rare. It mostly occurs in the first
years of life and in older age groups. Risk factors include male
sex, neurological disease, dental abnormalities and intoxication
with alcohol or medication (sedatives, anticholinergics,
antipsychotics). 3,4 In 2011, in the Netherlands, 4 children
and 50 adults died as a result of choking of which 51 by the
aspiration of food. More than 50% of this population was older
than 70 years of age. 5 However, the exact incidence of foreign
body aspiration is probably higher as many cases remain
undiagnosed. In a Finnish study six percent of the non-cardiac
originated cardiac arrests (34% of the cardiac arrests) were
due to choking.6 The majority of the aspirated foreign bodies
consist of food remains (organic matter). In several studies
peanuts and other nuts are the most common aspirated items
in the Western diet.1,4 This is different from the animal bone
fragments and fish bones in non-Western world studies.2,7
Symptoms
The location of the foreign body in the tracheobronchial tree
has a major influence on the presenting symptoms. Collapse
can be caused by foreign bodies in larynx or trachea. These
are relatively uncommon (5-10% of the aspirated foreign
bodies), but are asphyxiating and acutely life threatening. With
a complete closure of the airway a person has no ability to
speak or breathe and loss of consciousness and cyanosis often
develops rapidly (within 2-5 minutes).8,9,10 This is illustrated in
both cases described here. In adults, confusion with a cardiac
event frequently occurs. This common mistake is known as
the ‘cafe coronary’: after collapse in a restaurant, coronary
ischemia is suspected, while in fact foreign body aspiration is
the cause. The food which obstructs the airway mostly consists
of meat.11
The majority of the foreign bodies will pass through the
larynx and trachea and become lodged in the more peripheral
airways, mostly (40-50%) into the right main bronchus.
Frequently reported symptoms of foreign body aspiration, also
known as the penetration syndrome, are cough, dyspnoea,
vomiting and wheezing. These aspirations are not acutely life
threatening because of merely partial obstruction. Since they
are non-asphyxiating (and often less symptomatic or even
asymptomatic) these lower aspirations tend to be discovered
late, varying from days or weeks to even years.1,2,4,8,9,10
Diagnosis
When an asphyxiating foreign body aspiration is suspected
immediate airway control is needed. Pre-treatment diagnostics
will delay intervention and may worsen the outcome.
Immediate rigid bronchoscopy is the primary diagnostic and
therapeutic choice. This is discussed more extensively later on.
When suspecting a foreign body aspiration in the less acute
presentation, a conventional chest X-ray is the first imaging
modality of choice. A standard frontal view and lateral view
has to be obtained. Still, the clinician has to realize that an
aspirated foreign body is often not visible on the X-ray (5-50%).
Organic materials in particular are either not or reduced
radio-opaque. Air trapping or atelectasis can then be suggestive
of aspiration. Reliance on a negative X-ray can lead to increased
morbidity.1,12-14
CT scans have been demonstrated effective for detecting
foreign bodies. If a patient is suspected of having a foreign
body aspiration and has a negative chest X-ray, a thoracic
CT is justifiable. The correct diagnosis is made initially in
85% and retrospectively in 100%. The most reliable sign is a
demonstrated foreign body within the lumen. Radiologists
should also look for the compromise of patency of the bronchi,
atelectasis, bronchiectasis, hyperlucency and air trapping
which suggest aspiration.13,15
Diagnostic flexible bronchoscopy has been suggested as the
procedure of choice when foreign body aspiration is still
suspected or unexplained respiratory failure persists. Flexible
bronchoscopy allows precise identification and localization of
foreign bodies. Foreign body removal should not be attempted
during a diagnostic bronchoscopy unless the appropriate
equipment and personnel are available.9
Treatment
The primary goal with any aspiration is airway support and
control. Often the conscious patient will clear the airway by
coughing. Occasionally a visible object may be removed with
the fingers, however this has the risk of transforming a partial
obstruction into a complete obstruction. If the aspiration
persists, a blow between the shoulder blades and/or the
Heimlich manoeuvre can be applied. 3,10,12
When asphyxiation occurs (mostly due to complete obstruction)
mouth-to-mouth, bag valve mask ventilation or endotracheal
intubation should be attempted initially. Sometimes intubation
can push the obstructing foreign body into the right main
bronchus, allowing only the left lung to be ventilated.3,10,16
When a victim loses consciousness and has a cardiac arrest, the
airway may become accessible again by applying the jaw thrust
or as a result of BLS and the occurrence of muscle relaxation.
In a recent Japanese study, 78% of the cardiac arrests due to
food asphyxiation had return of spontaneous circulation
(ROSC) after CPR, yet only 7% survived to discharge. The
interval between asphyxiation and ROSC was in all survivors
10 minutes or less.17 Further treatment should be dependent on
the location of the object, clinical presentation and degree of
obstruction.10
Acute complete airway obstruction, usually laryngeal or
tracheal and asphyxiating, demands prompt treatment by
early removal of the obstructing object or on re-establishing
an airway. In advanced life support (ALS) and having the aid
of a laryngoscope or a gripping tool (for example the Magill
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Netherlands Journal of Critical Care
forceps), residues deeper in the hypopharynx can be obtained.
However, when the acute obstruction persists a cricothyroidotomy or emergency tracheotomy will be needed. This is
only useful when the obstruction is located above the level
of the true vocal cords (cricothyroidotomy) or slightly lower
when a tracheotomy can be placed some cartilage rings below
the glottis. Emergency cricothyroidotomy is performed in
approximately 1% of all emergency airway cases in the ED. The
success rate for the acute cricothyroidotomy is 66-100%.This
is significantly higher than the needle cricothyroidotomy.18,19
Foreign bodies in the trachea are less accessible. Sometimes
the foreign body may be grasped with forceps, but generally an
immediate rigid bronchoscopy is required. Rigid bronchoscope
offers, especially in the upper tracheobronchial tree, better
access for more extensive diagnostics, rapid intervention and
airway control (endotracheal ventilation possibilities). The
large working channel and variety of instruments leads to a
successful extraction rate of 95-98%. A disadvantage is the
need for general anaesthesia and relaxation.4,9,12,14 In both our
patients, we did not perform rigid bronchoscopy, because on
arrival at the hospital the airway obstruction had already been
resolved.
Bronchial foreign bodies are generally less acute in presentation
and radiological assessment is warranted first. When the
location of the foreign body has been established, extraction
through flexible bronchoscopy must ensue without delay. Early
bronchoscopy is essential to reduce complications.9,12 Based
on the literature, there is increasing preference for flexible
bronchoscopy in a less urgent aspiration given the relative
ease and safety. Furthermore, flexible bronchoscopy can be
performed under local anaesthesia and can extend beyond the
main bronchi. It has a success rate of 60-100%.4,7,8 If flexible
bronchoscopy (diagnostic or therapeutic) is attempted, it has to
be performed in a room equipped for resuscitation, definitive
airway management, mechanical ventilation and rigid
bronchoscopy in case a complete central airway obstruction
occurs. A disadvantage of the flexible bronchoscope is the
smaller working channel and thus more difficulty with removal
of bigger objects. 3,4,7,9,12,14
Extraction can be complicated when a foreign body is encased
by granulation tissue. In these cases it may be useful to
postpone the extraction for 12-24 hours and start intravenous
corticosteroids, but controversy still exists. Some studies
also suggest putting patients on a regime of antibiotics,
bronchodilators and corticosteroids after removal of the
foreign body.8,9
Surgery, mostly a lobectomy, should be performed only as a last
resort but is sometimes unavoidable. This is generally caused
by a delay in treatment resulting in severe bronchiectasis and
bronchoscopic failure.12
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N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
Conclusion
Acute foreign body aspiration should be considered in
the differential diagnosis of an acute collapse eci. When
asphyxiation occurs immediate actions are vital, however the
possibility of foreign body aspiration in collapse is not always
considered. The primary goal of any aspiration is removing
the object that obstructs the airway and re-establishing an
airway as soon as possible. The gold standard in treating an
asphyxiating foreign body aspiration is rigid bronchoscopy.
References
1.
Tan HKK, Brown K, McGill T, Kenna MA, Lund DP, Healy GB. Airway foreign bodies
(FB): a 10-year review. Int. J. Pediatr. Otorhinolaryngol. 2000;56:91-99.
2.
Chen CH, Lai CL, Tsai TT, Lee YC, Perng RP. Foreign body aspiration into the lower
airway in Chinese adults. Chest. 1997;112:129-133.
3.
Boyd M, Chatterjee A, Chiles C, Chin R. Tracheobronchial foreign body aspiration
in adults. Southern Medical Journal. 2009;102:171-174.
4.
Limper AH, Prakash UBS. Tracheobronchial foreign bodies in adults.
1990;112:604-609.
5.
Dutch Central Bureau of Statistics. Extensive list of causes of death, 2011. http://
statline.cbs.nl
6.
Kuisma M, Alaspaä A. Out-of-hospital cardiac arrests of non-cardiac origin.
European Heart Journal. 1997;18:1122-1128.
7.
Mise K, Savicevic AJ, Pavlov N, Jankovic S. Removal of tracheobronchial foreign
bodies in adults using flexible bronchoscopy: experience 1995-2006. Surg.
Endosc. 2009;23:1360-1364.
8.
Baharloo F, Veyckemans F, Francis C, Biettlot M, Rodenstein D. Tracheobronchial
foreign bodies. Chest. 1999;115:1357-1362.
9.
Marquette C, Parsons PE, Finlay G. Airway foreign bodies in adults. Uptodate.
com. Febr 2013.
10. Stark DCC, Biller HF. Int. Anesthesiol. Clin. 1977;15:117-145.
11. Haugen RK. The cafe coronary: sudden deaths in restaurants. JAMA.1963;186:142143.
12. Sahin A, Meteroglu F, Eren S, Celik Y. Inhalation of foreign bodies in children:
experience of 22 years. J Trauma Acute Care Surg. 2013;74:658-63
13. Zissin R, Shapiro-Feinberg M, Rozenman J, Apter S, Smorjik J, Hertz M. CT
findings of the chest in adults with aspirated foreign bodies. Eur. Radiol.
2001;11:606-611.
14. Swanson, KL. Airway Foreign Bodies: What’s new? Semin Respir Crit Care Med.
2004;25:405-11.
15. Kavanagh PV, Mason AC, Müller NL. Thoracic Foreign Bodies in Adults. Clinical
Radiology. 1999;54:353-360.
16. Dutch National Protocol for Ambulances, revised version 7.2, March 2011 (in
Dutch).
17. Inamasu J, Miyatake S, Tomioka H, Shirai T, Ishiyama M, Komagamine J et al.
Cardiac arrest due to food asphyxiation in adults: resuscitation profiles and
outcomes. Resuscitation. 2010;21:1082-1086.
18. Bair AE, Panacek EA, Wisner DH, Bales R, Sakles JC. Cricothyrotomy: a 5-year
experience at one institution. J. Emerg. Med. 2003;24:151-156.
19. Hubble MW, Wilfong DA, Brown LH, Hertelendy A, Benner RW. A meta-analysis
of prehospital airway control techniques part II: alternative airway devices and
cricothyrotomy success rates. Prehosp. Emerg. Care. 2010;14:515-530.
Netherlands Journal of Critical Care
Accepted 2012
P R O / C ON
Non Invasive Ventilation; PROs and CONs
A.F. van der Sluijs
Department of Intensive Care, Academic Medical Center, Amsterdam, The Netherlands
Correspondence
A.F. van der Sluijs – e-mail: [email protected]
Keywords - Non invasive ventilation, NIV, mechanical ventilation, acute-on-chronic respiratory failure
Introduction
Mechanical ventilation is required for patients with acute or
acute-on-chronic respiratory failure that does not respond to
standard therapeutic interventions such as administration
of antibiotics, diuretics, bronchodilators and – not to be
forgotten – oxygen. The majority of patients requiring
ventilatory support are intubated and ventilated invasively.
Actually we do regard this as conventional mechanical
ventilation. Although initiating invasive mechanical ventilation
can be a life-saving intervention, it is just supportive rather
than curative and gives us the chance to treat underlying
disease. In contrast, conventional mechanical ventilation is
associated with several complications, related to the intubation
as well as to the risk of developing a ventilator-associated
pneumonia (VAP). In order to avoid these risks, an alternative
to conventional mechanical ventilation was invented in the
nineteen-eighties known as Non Invasive Ventilation (NIV).
With NIV, a nasal or face mask is used to deliver ventilatory
support to the patient instead of an endotracheal tube. Since
its introduction, NIV has been applied in different ventilator
modes to many different patient categories with acute,
acute-on-chronic and even chronic respiratory failure, both
within and outside the Intensive Care environment.
To determine the value of a certain therapy, one has to consider
its advantages and disadvantages and, if possible compare it
with conventional treatment. In the text below I would like
to focus on the disadvantages of Non Invasive Mechanical
Ventilation for acute or acute-on-chronic respiratory failure
within the Intensive Care Unit.
Disadvantages of Non Invasive Ventilation
One of the issues associated with NIV is that it is not appropriate
for all patients. Cooperation of the patient is paramount
which means that timely referral to the Intensive Care Unit
is essential and this is exactly where the rub is. Patients with
imminent respiratory failure are kept in general wards as long
as they do not meet the criteria for admittance to the Intensive
Care Unit. It is therefore very hard to predict which patients
will make it without ventilator support and which patients
will eventually deteriorate. In my experience, many patients
who would have been candidates for NIV are transferred to
the ICU when intubation and invasive mechanical ventilation
is the only remaining option. NIV is not appropriate for
patients with: respiratory arrest, haemodynamic instability or
multiple organ failure, recent upper airway- or upper gastrointestinal surgery or bleeding, excessive sputum production
or a diminished cough reflex or swallowing impairment. As
mentioned above, uncooperative or agitated patients are not
eligible for NIV. Some authors suggest the use of sedation in
mildly agitated or anxious patients, although this may increase
the risk of aspiration and potentially worsen hypoventilation.
A well-known disadvantage of NIV is leakage. Although most
ventilators have NIV modes with adapted alarm settings,
it remains unclear how much ventilation we actually deliver
to our patients. End-tidal carbon dioxide measurement is
unreliable and adjustments to the ventilator setting might
as well improve ventilation as worsen it by an increase in
the amount of leakage. Frequent arterial blood sampling is
mandatory and therefore most patients on NIV will have an
arterial line inserted. Leakage on the top side of nasal or full
face masks may result in dry eyes and conjunctivitis.
Patients on NIV have an increased risk of aspiration. Compared
with intubated patients they do not have a secured airway and
as a result of alternating positive pressures in the nasal- and
oropharyngeal cavity, gastric distension may occur, herewith
increasing the risk of aspiration. Insertion of a nasogastric tube
reduces the risk of gastric distention and aspiration, but may
adversely affect the problem of leakage.
Many patients experience discomfort when they are intubated
and mechanically ventilated and this argument is often used as
highlighting the benefit of NIV; also, there would be no need
for sedation. However, NIV may lead to substantial discomfort
as well, particularly as a result of pressure, which may even lead
to ulcers.
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Netherlands Journal of Critical Care
What level of evidence is available in the literature to support
the use of Noninvasive Positive Pressure Ventilation (NPPV)
in the various causes of acute respiratory failure? In 1997, both
authors conducted a meta-analysis on this subject which was
published in Critical Care Medicine.2 In summary, the general
conclusion was that beyond the COPD population, there was, at
that time, insufficient evidence to support the use of NPPV in
acute respiratory failure. The reviewed randomized controlled
trials were generally small and in most studies NIV was
compared with conventional therapy, meaning administration
of supplemental oxygen. Endpoints in the studies differed
from the need for intubation, ICU and hospital length of stay
and mortality. During the first decade of this century, more
RCTs were conducted and NIV seems to be beneficial in more
patient categories3: patients with severe or mild exacerbations
of COPD, patients with cardiogenic pulmonary oedema,
immunocompromised patients and patients with failure to
wean (NIV after extubation). However, in 2011, Girault et
al. found no benefit of NIV in different weaning strategies.4
Moreover, NIV was used as a rescue strategy when acute
post-extubation respiratory failure occurred in the invasive
weaning and supplemental oxygen group and was successful in
45 and 58% respectively.
Finally, an important disadvantage of NIV in the ICU is the
burden for the caregiver, in particular the nurse. Patients on
NIV need a lot of attention and specific care which is not a
problem as long as the attending nurse is experienced and not
occupied with other patients. Insufficient attention for patients
on NIV may lead to inadequate treatment with the risk of
deterioration of the patient’s condition.
Literature
We do live in a time of evidence based medicine, so what
does the literature teach us about the value of NIV? During
the nineteen-nineties a lot of papers about NIV appeared in
medical journals and in 1998 Sean Keenan and David Brake
reviewed.1 the available data and posed the following question:
28
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Discussion
Non Invasive Ventilation is used to treat acute respiratory
failure without the insertion of an endotracheal tube. In this
context NIV is an excellent alternative for patients with “do not
intubate” orders. There are, however, various other reasons why
doctors prefer not to intubate a particular patient and in a lot of
studies on NIV the need for intubation is a primary endpoint.
An objection against many studies is that NIV is compared
with “standard medical treatment” and I found only one RCT
with NIV compared to invasive ventilation. Imagine one
hundred patients with acute (or acute-on-chronic) respiratory
failure starting with NIV. 40 of these patients deteriorate and
meet the criteria for intubation. The question is how to describe
this result: was NIV successful in 60%, because the ultimate
goal was to avoid intubation? Or was there a 40% failure of the
initiated therapy (NIV)?
The use of NIV has proven to be beneficial in some patients but
even considering this, we need strict inclusion and exclusion
criteria. In general we should apply NIV only for short-term
respiratory failure, when we are able to treat the underlying
disease within hours. On the ICU, I frequently see patients
with acute respiratory failure, transferred from general wards,
where NIV would have been an option a few hours earlier. Too
often we are simply too late.
Patients who are actually treated with NIV should be
strictly monitored, including frequent blood sampling and
it is questionable whether or not this can be done on general
pulmonary wards. The effect of the NIV treatment should be
Netherlands Journal of Critical Care
Non Invasive Ventilation; PROs and CONs
closely monitored and if there is no improvement patients have
to be intubated before they are completely exhausted.
The disadvantages of NIV vary from leakage, which makes the
treatment less reliable, to discomfort and pressure ulcers. The
main disadvantage of NIV is that the therapy is not suitable
for all patients and can be applied for only a limited period
(hours). These issues should be weighed against the risks and
complications of invasive mechanical ventilation, but what we
actually need are large multicenter randomized trials where
non-invasive and invasive ventilation are compared with
hospital mortality as a primary endpoint.
References
1.
Keenan SP, Brake D. An evidence-based approach to noninvasive ventilation in
acute respiratory failure. Crit Care Clin. 1998;14(3):359-72
2.
Keenan SP, Kernerman PD, Cook DJ, et al. The effect of noninvasive positive
pressure ventilation on mortality in patients admitted with acute Respiratory
failure: A meta-analysis. Crit Care Med. 1997;25:1685-92
3.
Nava S, Hill, NS. Non-invasive ventilation in acute respiratory failure. Lancet
2009;374:250-59
4.
Girault C, Bubenheim M, Abroug F, et al. Noninvasive ventilation and weaning in
patients with chronic hypercapnic respiratory failure: a randomized multicenter
trial. Am J Respir Crit Care Med. 2011;184(6):672-9.
Disclaimer
The author reports no conflicts of interest and was invited to
focus on the CONs of Non Invasive Ventilation. The statements
above do not necessarily represent the author’s opinion.
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
29
Netherlands Journal of Critical Care
C L I N I C AL I MA G E
A traumatic aneurysm of the pericallosal artery
A.C. van Dijk1, W-J. van Rooij2, A.M.F. Rutten3
Department of Radiology, Erasmus University Medical Center, Rotterdam
1
2
Department of Intensive Care Medicine, St Elisabeth Hospital, Tilburg, The Netherlands
3
Department of Radiology, St Elisabeth Hospital, Tilburg, The Netherlands
Correspondence
A.M.F. Rutten – e-mail: [email protected]
Keywords - Intracerebral hemorrhage, brain trauma, traumatic aneurysm, peicallosal artery aneurysm
A 28-year-old man hit a deer while driving his car. He was
found comatose at 25 meters distance from the damaged car.
On admission his Glasgow Coma Score was 5 (E1M3V1). A
computer tomography (CT) scan showed a large haematoma
in the corpus callosum ( figure 1) without skull fractures. In
addition, there was a severe lung contusion with multiple
rib fractures. The location of the cerebral bleeding raised
the suspicion of a false aneurysm. His respiratory condition
required high pressure ventilation, which made early
angiography impossible. After 6 days his respiratory
condition had stabilized. Cerebral angiography revealed a
2 mm false aneurysm on the right distal pericallosal artery
with circumferential involvement of the small vessel ( figure
2, arrow). Apparently, the artery was torn under the sharp
free edge of the falx cerebri. Endovascular parent vessel
occlusion or trapping were considered the only possible
therapies in this patient. A microcatheter was navigated just
proximal to the aneurysm and a small amount of n-butylcyanoacrylate glue (Histo-acryl, Braun, Melsungen, Germany)
mixed with Lipiodol (Guerbet, Rossy, France) was injected. The
glue first occluded the parent artery distal to the aneurysm
and subsequent reflux occluded the aneurysm itself and the
proximal parent vessel ( figure 3, glue in the aneurysm (arrow)
as well as in the proximal and distal parent artery). A control
angiogram confirmed the exclusion of the aneurysm from the
circulation. The patient was weaned from the respirator. An
intensive rehabilitation followed in subsequent months after
which he made a reasonably good recovery. The function of his
left hand was still impaired and he had difficulty speeking. He
is currently at home and one year later, he is learning how to
drive again in an adjusted car.
Traumatic intracranial aneurysms are rare; approximately 1
percent of all intracranial aneurysms are traumatic.1 Traumatic
intracranial aneurysms are most commonly described
after penetrating brain injury; approximately 20 percent
30
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
Figure 1.
Figure 2.
Figure 3.
Netherlands Journal of Critical Care
A traumatic aneurysm of the pericallosal artery
of traumatic aneurysms after traumatic brain injury are
caused by penetrating brain injury.2 Nevertheless, traumatic
intracranial aneurysms can be seen after closed head trauma
as well. Severe closed head trauma may damage an intracranial
artery adjacent to a (fractured) bony structure or sharp edge of
the dura. The most common locations of traumatic aneurysms
in the absence of fractures are the internal carotid artery next
to the clinoid process and the pericallosal artery alongside
the free edge of the falx.2 When the arterial tear is across the
entire vessel wall, the arterial rupture will cause an immediate
haemorrhage, as in our patient. With partial disruption of
the arterial wall, delayed haemorrhage may occur when the
pseudo-aneurysm later ruptures.1 Mortality rates as high as 50
percent are described due to delayed intracranial haemorrhage.
Traumatic aneurysms represent a surgical challenge due
to unusual locations, thin walls, and poorly defined necks
in a frequently unfavourable clinical setting. In contrast,
endovascular treatment is usually straightforward.4 Since after
selective coiling the traumatic aneurysm may keep on growing
with possible repeat haemorrhage, endovascular parent vessel
occlusion with glue or coils, is the treatment of choice wherever
possible.5,6
The pericallosal artery, the part of the anterior cerebral artery
distal to the anterior communicating artery is the primary
supplier of blood to the midline of the brain, vascularizing the
corpus callosum, the optodiencephalic area, and the anterior
two thirds of the medial and superomedial aspects of both
hemispheres. Various anatomical variations of the pericallosal
arterial complex are described. Obliteration of the same
arterial segment may or may not produce important clinical
consequences, depending on the available blood-supplying
channels.7 Contralateral hemiparesis with lower limb
predominance, speech disturbances, psychomotor slowing
and apraxia are the most common symptoms in patients with a
pericallosal artery infarction.8
References
1.
O’Brien D Jr, O’Dell MW, Eversol A. Delayed traumatic cerebral aneurysm after
brain injury. Arch Phys Med Rehabil 1997;78:883-885.
2.
Nakstad PH, Gjertsen O, Pedersen HK. Correlation of head trauma and traumatic
aneurysms. Interv Neuroradiol 2008;14:33-38.
3.
O’Brien D Jr, O’Dell MW, Eversol A. Delayed traumatic cerebral aneurysm after
brain injury. Arch Phys Med Rehabil 1997;78:883-885.
4.
Cohen JE, Gomori JM, Segal R, et al. Results of endovascular treatment of traumatic intracranial aneurysms. Neurosurgery 2008;63:476-485.
5.
Ngo DQ, van Rooij WJ, Tijssen C. Rapidly growing traumatic cerebral aneurysm
with early subarachnoid hemorrhage. Neurology 2008;70:490.
6.
Yuen CM, Kuo YL, Ho JT, Liao JJ. Rapid regrowth of a successfully coiled traumatic pericallosal aneurysm. J Clin Neurosci 2007;14:1215-1219.
7.
Kakou M, Destrieux C, Velut S. Microanatomy of the pericallosal arterial complex.
J Neurosurg. 2000;93:667-75
8.
Alonso A, Gass A, Rossmanith C. Clinical and MRI patterns of pericallosal artery
infarctions: the significance of supplementary motor area lesions. J. Neurol
2012;259:944-51.
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
31
Netherlands Journal of Critical Care
Editorial Board of the Netherlands Journal of Critical Care
A.B. Johan Groeneveld, Editor
in Chief
Dept. of Intensive Care Medicine
Erasmus Medical Center
Rotterdam
PO Box 2040
3000 CA Rotterdam
Wolfgang Buhre, Section Editor
Anesthesiology
Dept. of Anesthesiology
University Medical Center
Utrecht
PO Box 85500
3508 GA Utrecht
Jan Bakker, Section Editor
Hemodynamics
Dept. of Intensive Care Medicine
Erasmus Medical Center
Rotterdam
PO Box 2040
3000 CA Rotterdam
Hans van der Hoeven, Section
Editor
Mechanical Ventilation
Dept. of Intensive Care Medicine
Radboud University Nijmegen
Medical Centre
PO Box 9101
6500 HB Nijmegen
Alexander Bindels, Section Editor
Endocrinology
Dept. of Internal Medicine
Catharina Hospital
Michelangelolaan 2
5623 EJ Eindhoven
Bert Bos, Section Editor
Pediatrics
Department of Pediatrics
Academic Medical Center
University of Amsterdam
Meibergdreef 9
1105 AZ Amsterdam
Frank Bosch, Section Editor
Imaging
Dept. of Internal Medicine
Rijnstate Hospital
PO Box 9555
6800 TA Arnhem
Can Ince, Section Editor
Physiology
Dept. of Physiology
Academic Medical Center
University of Amsterdam
Meibergdreef 9
1105 AZ Amsterdam
Evert de Jonge, Section Editor
Scoring and quality assessment
Dept. of Intensive Care Medicine
Leiden University Medical Center
P.O. Box 9600
2300 RC Leiden
Nicole Juffermans
Section Editor
Hemostasis and Thrombosis
Dept. of Intensive Care
Academic Medical Center
University of Amsterdam
Meibergdreef 9
1105 AZ Amsterdam
Heleen Oudemans-van Straaten,
Section Editor Nephrology
Dept. of Intensive Care Medicine
VU University Medical Center
PO Box 7057
1007 MB Amsterdam
Peter Pickkers, Section Editor
Sepsis and inflammation
Dept. of Intensive Care Medicine
Radboud University Nijmegen
Medical Centre
PO Box 9101
6500 HB Nijmegen
Arjen Slooter, Section Editor
General
Dept. of Intensive Care
University Medical Center
Utrecht
PO Box 85500
3508 GA Utrecht
Peter Spronk, Section Editor
General
Dept. of Intensive Care Medicine
Gelre Hospital, location Lukas
PO Box 9014
7300 DS Apeldoorn
Jaap Tulleken, Section Editor
General
Dept. of Intensive Care Medicine
University Medical Center
Groningen
PO Box 30001
9700 RB Groningen
Anton van Kaam, Section Editor
Neonatology
Dept. of Neonatal Intensive Care
Emma Children’s Hospital,
Academic Medical Center
University of Amsterdam
Meibergdreef 9
1105 AZ Amsterdam
Jozef Kesecioglu, Section Editor
Pulmonology
Dept. Of Intensive Care Medicine
University Medical Center
Utrecht
PO Box 85500
3508 GA Utrecht
Michael Kuiper, Section Editor
Neurology
Dept. of Intensive Care Medicine
Medical Center Leeuwarden
PO Box 888
8901 BR Leeuwarden
Maarten Nijsten, Section Editor
Surgery
Dept. of Intensive Care Medicine
University Medical Center
Groningen
PO Box 30 001
9700 RB Groningen
International Advisory Board
Charles Gomersall
Dept. of Anaesthesia and Intensive
Care
The Chinese University of Hong
Kong, Prince of Wales Hospital
Hong Kong, China
Frank van Haren
A/ Professor, Australian National
University Medical School
Department of Intensive Care
Medicine
The Canberra Hospital
PO Box 11, Woden, ACT 2606
Canberra, Australia
Charles Hinds
Professor of Intensive Care
Medicine
St. Bartholomew’s Hospital
West Smithfield, London, UK
32
Patrick Honoré
Heads of Clinics
Director of Critical Care
Nephrology Platform
ICU department
Universitair Ziekenhuis Brussel,
VUB University
Brussels, Belgium
Alun Hughes
Professor of Clinical
Pharmacology
Imperial College London
South Kensington Campus
London, UK
Manu Malbrain
Dept. of Intensive Care Unit
Hospital Netwerk Antwerp
Campus Stuivenberg
Antwerp, Belgium
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
Paul Marik
Associate Professor
Dept. of Medicine and Medical
Intensive Care Unit
University of Massachusetts
St. Vincent’s Hospital, USA
Greg Martin
Dept. of Medicine
Division of Pulmonary, Allergy and
Critical Care
Emory University School of
Medicine
Atlanta, USA
Ravindra Mehta
Professor of Clinical Medicine
Associate Chair for Clinical
Research
Department of Medicine
UCSD Medical Centre
8342, 200 W Arbor Drive
San Diego, USA
Xavier Monnet
Service de réanimation médicale
Centre Hospitalier Universitaire
de Bicêtre
France
Jean-Charles Preiser
Dept. Intensive Care
CHU Liege – Domaine
Universitaire
Liege, Belgium
Yasser Sakr
Dept. of Anaesthesiology and
Intensive Care
Friedrich-Schiller University
Hospital
Jena, Germany
Hannah Wunsch
Dept. of Anaesthesia
New York Presbyterian Columbia
New York, USA
Martini Ziekenhuis Groningen zoekt…
8e intensivist
Vanwege uitbreiding van het aantal IC-bedden zoeken wij een gedreven nieuwe intensivist,
die onze intensivistenvakgroep voltallig maakt.
De intensive care van het Martini Ziekenhuis is een closed format niveau 3 intensive care met
achttien bedden. De intensivisten zijn ook verantwoordelijk voor de patiëntenzorg op de ICbedden in het Brandwondencentrum.
Er is een enthousiast, jong, multidisciplinair intensivistenteam met zeven intensivisten
(interne geneeskunde, anesthesiologie en longziekten). Op onze afdeling, inclusief het
Brandwondencentrum, werken twaalf arts-assistenten. Onze afdeling is een gemengd medische en chirurgische intensive care met vrijwel alle faciliteiten en heeft een regiofunctie
voor vaatchirurgie, longchirurgie, neurochirurgie en complexe gastro-intestinale chirurgie.
Het Brandwondencentrum heeft een landelijke functie.
Belangstelling?
Voor meer informatie verwijzen wij u naar www.martiniziekenhuis.nl. U kunt ook telefonisch contact opnemen met
de dienstdoende intensivist, tel. ()  .
Uw schriftelijke sollicitatie en curriculum vitae kunt u sturen naar het secretariaat Raad van Bestuur Martini Ziekenhuis,
ter attentie van mw. H. Swaving, secretaresse Toelatingscommissie, Postbus ,  RM Groningen.
Graag ontvangen wij uw brief binnen drie weken na plaatsing van deze advertentie.
www.martiniziekenhuis.nl
hypoxie, rhonchi, wheezing, buikpijn, pijn in de bovenbuik, droge mond,
dyspepsie, last van de maag, opgezwollen buik, ascites, constipatie,
dysfagie, winderigheid, cholestase, hepatomegalie, hyperbilirubinemie,
geelzucht, gestoorde leverfunctie, hepatotoxiciteit, leveraandoening,
erythema multiforme, maculaire uitslag, maculopapulaire uitslag,
pruritische uitslag, urticaria, allergische dermatitis, gegeneraliseerde
pruritus, erythemateuze uitslag, gegeneraliseerde uitslag, morbilliforme
uitslag, huidlaesie, rugpijn, pijn in extremiteiten, botpijn, spierzwakte,
myalgie, nierfalen, acuut nierfalen, pijn, pijn rond catheter,
vermoeidheid, koud gevoel, warm gevoel, erytheem op infusieplaats,
verharding op infusieplaats, pijn op infusieplaats, zwelling op
infusieplaats, flebitis op injectieplaats, perifeer oedeem, gevoeligheid,
ongemak op de borst, pijn op de borst, aangezichtsoedeem, gevoel
van andere lichaamstemperatuur, verharding, extravasatie op
infusieplaats, irritatie op infusieplaats, flebitis op infusieplaats, uitslag
op infusieplaats, urticaria op infusieplaats, erytheem op injectieplaats,
oedeem op injectieplaats, pijn op injectieplaats, zwelling op
injectieplaats, malaise, oedeem.
Onderzoeken:
Vaak: verlaagd kalium in bloed, verlaagd bloedalbumine.
Soms: verhoogd bloedcreatinine, positief voor rode bloedcellen in
urine, verlaagd totaal eiwit, eiwit in urine, verlengde protrombinetijd,
verkorte protrombinetijd, verlaagd natrium in bloed, verhoogd natrium
in het bloed, verlaagd calcium in bloed, verhoogd calcium in bloed,
verlaagd chloride in bloed, verhoogd glucose in bloed, verlaagd
magnesium in bloed, verlaagd fosfor in bloed, verhoogd fosfor in bloed,
verhoogd ureum in bloed, verhoogd gamma-glutamyltransferase,
verlengde geactiveerde partiële tromboplastinetijd, verlaagd
bicarbonaat in bloed, verhoogd chloride in bloed, verhoogd kalium
in bloed, verhoogde bloeddruk, verlaagd urinezuur in bloed, bloed in
urine, afwijkende ademgeluiden, verlaagd kooldioxide, verhoogde
concentratie immunosuppressivum, verhoogde INR, cilinders in
urinesediment, positief op witte bloedcellen in urine, en verhoogde
pH van urine.
Kinderen
Het algehele veiligheidsprofiel van CANCIDAS bij kinderen is over het
algemeen vergelijkbaar met dat bij volwassenen.
Zeer vaak: koorts.
Vaak: verhoogd aantal eosinofielen, hoofdpijn, tachycardie, flushing,
hypotensie, verhoogde leverenzymen (AST, ALT), uitslag, pruritus,
rillingen, pijn op de injectieplaats.
Onderzoeken:
Vaak: verlaagd kalium, hypomagnesiëmie, verhoogd glucose, verlaagd
fosfor en verhoogd fosfor.
Post-marketingervaring
Sinds de introductie van het product zijn de volgende bijwerkingen
gemeld:
leverfunctiestoornis, zwelling en perifeer oedeem, hypercalciëmie.
Farmacotherapeutische groep
Antimycotica voor systemisch gebruik, ATC-code: J 02 AX 04
Afleverstatus
UR
Verpakking
CANCIDAS 50 mg is beschikbaar in een verpakking met
1 injectieflacon.
CANCIDAS 70 mg is beschikbaar in een verpakking met
1 injectieflacon.
Vergoeding
CANCIDAS wordt volledig vergoed.
Raadpleeg de volledige productinformatie (SPC) voor meer informatie
over CANCIDAS.
Verkorte productinformatie ECALTA (september 2012). De volledige productinformatie (SPC van 23 augustus 2012) is op aanvraag verkrijgbaar.
Samenstelling: ECALTA bevat 100 mg anidulafungin per injectieflacon, overeenkomend met een 3,33 mg/ml oplossing na reconstitutie
met water voor injecties. De verdunde oplossing bevat 0,77 mg/ml anidulafungin. Indicaties: Behandeling van invasieve candidiasis
bij volwassen niet-neutropenische patiënten. ECALTA is hoofdzakelijk onderzocht bij patiënten met candidemie en slechts bij een
beperkt aantal patiënten met diepgelegen Candida infecties of met abcesvorming. Farmacotherapeutische groep: Antimycotica voor
systemisch gebruik, andere antimycotica voor systemisch gebruik, ATC-code: JO2 AX 06. Dosering: De behandeling met ECALTA
moet worden uitgevoerd door een arts die ervaring heeft met de behandeling van invasieve schimmelinfecties. De eenmalige
aanvangdosis van 200 mg dient op dag 1 te worden toegediend, daarna gevolgd door dagelijks 100 mg. Er zijn onvoldoende gegevens
beschikbaar om een behandeling van langer dan 35 dagen met de 100 mg dosis te onderbouwen. De veiligheid en werkzaamheid
van ECALTA bij kinderen jonger dan 18 jaar zijn niet vastgesteld. Op basis van de momenteel beschikbare gegevens kan geen
doseringsadvies worden gedaan. Het wordt aanbevolen om ECALTA toe te dienen met een infusiesnelheid die niet hoger is dan 1,1
mg/minuut (overeenkomend met 1,4 ml/minuut wanneer gereconstitueerd en verdund conform instructies). ECALTA mag niet worden
toegediend als een bolusinjectie. Contra-indicaties: Overgevoeligheid voor het werkzame bestanddeel of voor één van de hulpstoffen;
overgevoeligheid voor andere geneesmiddelen uit de groep van echinocandinen. Waarschuwingen en voorzorgen: De werkzaamheid
van ECALTA bij neutropenische patiënten met candidemie en bij patiënten met diepgelegen Candida infecties of intra-abdominaal
abces en peritonitis is niet vastgesteld. De klinische werkzaamheid is hoofdzakelijk beoordeeld bij niet-neutropenische patiënten
met C. albicans infecties en bij een kleiner aantal patiënten met niet-albicans infecties, voornamelijk C. glabrata, C. parapsilosis en
C. tropicalis. Patiënten met Candida-endocarditis, -osteomyelitis of -meningitis en bekende C. krusei infectie zijn niet onderzocht.
Verhoogde waarden van leverenzymen zijn waargenomen bij gezonde personen en patiënten die met anidulafungin werden behandeld.
Bij een aantal patiënten met een ernstige onderliggende medische aandoening die gelijktijdig meerdere geneesmiddelen kregen
naast anidulafungin, zijn klinisch significante leverafwijkingen opgetreden. Gevallen van significante leverstoornis, hepatitis en
leverfalen kwamen soms voor tijdens klinische onderzoeken. Bij patiënten met verhoogde leverenzymen tijdens behandeling met
anidulafungin dient te worden gecontroleerd op tekenen van verslechterende leverfunctie en dient het risico/voordeel van voortzetting
van behandeling met anidulafungin geëvalueerd te worden. Anafylactische reacties, waaronder shock, zijn gemeld bij het gebruik
van anidulafungin. Indien deze reacties voorkomen, dient de behandeling met anidulafungin te worden stopgezet en dient passende
behandeling te worden gegeven. Infusiegerelateerde bijwerkingen zijn gemeld bij het gebruik van anidulafungin, waaronder uitslag,
urticaria, blozen, pruritus, dyspneu, bronchospasmen en hypotensie. Infuusgerelateerde bijwerkingen komen weinig voor wanneer de
snelheid waarmee anidulafungin wordt geïnfundeerd niet hoger is dan 1,1 mg/minuut. In een onderzoek bij ratten is verergering van
infusie-gerelateerde reacties door gelijktijdige behandeling met anesthetica waargenomen waarvan de klinische relevantie onbekend
is. Men dient voorzichtig te zijn bij het gelijktijdig toedienen van anidulafungin en anesthetica. Patiënten met een zeldzame erfelijke
fructose-intolerantie dienen dit geneesmiddel niet te gebruiken. Bijwerkingen: Bijwerkingen in klinische studies waren meestal licht
tot matig en leidden zelden tot stopzetting van de behandeling. De meest gerapporteerde, vaak voorkomende bijwerkingen (≥1/100
tot <1/10) zijn: coagulopathie, convulsies, hoofdpijn, diarree, braken, misselijkheid, verhoogd creatininegehalte in het bloed, uitslag,
pruritus, hypokaliëmie, flushing, verhoogde alanine-aminotransferase, verhoogde alkalische fosfatase in het bloed, verhoogde
aspartaat-aminotransferase, verhoogd bilirubine in het bloed, verhoogde gamma-glutamyltransferase. Soms (≥1/1000, < 1/100) zijn
waargenomen: pijn in de bovenbuik, urticaria, hyperglykemie, hypertensie, opvliegers, pijn op de infusieplaats, cholestase. Bijwerkingen
uit spontane meldingen met frequentie niet bekend (kan met de beschikbare gegevens niet worden bepaald) zijn: anafylactische
shock, anafylactische reactie (zie “Waarschuwingen en voorzorgen”), hypotensie, bronchospasmen, dyspneu. Afleveringsstatus:
UR. Verpakking en Registratienummer: ECALTA, 100 mg poeder voor concentraat voor oplossing voor intraveneuze infusie:
EU/1/07/416/002 (1 injectieflacon met 100 mg poeder). Vergoeding en prijzen: ECALTA wordt vergoed volgens de ‘Beleidsregel dure
geneesmiddelen in ziekenhuizen’. Voor prijzen wordt verwezen naar de Z-Index taxe. Voor medische informatie over dit product belt
u met 0800-MEDINFO (6334636). Registratiehouder: Pfizer Limited, Ramsgate Road, Sandwich, Kent CT13 9NJ, Verenigd Koninkrijk.
Neem voor correspondentie en inlichtingen contact op met de lokale vertegenwoordiger: Pfizer bv, Postbus 37, 2900 AA
Capelle a/d IJssel.
1. Reboli AC et all; Anidulafungin Study Group. Anidulafungin versus fluconazole for invasive candidiasis. New England Journal of
Medicine 2007;356(24):2472-82*. 2. Glöckner et all, Treatment of invasive candidiasis with echinochandines. Mycoses 2009 pag
476-486. 3. Ecalta Sept 2011 Summary of Product Characteristics. 4. www.cvz.nl. 5. Taxe April 2012, WMG-geneesmiddelen Z-Indez,
13e jaargang nr. 8. 6. Stichting Werkgroep Antibioticabeleid (SWAB), Optimaliseren van het antibioticabeleid in Nederland XII, SWABrichtlijnen voor de behandeling van invasieve schimmelinfecties,September 2008. 7. Joseph J.M et all; Anidulafungin: a drug evaluation
of a new echinocandin; Expert opinion Informa health care 2008; 2339-2348.
*In deze studie werd anidulafungin-IV vergeleken met fl uconazol-IV bij 245 patienten met invasieve candidiasis. Het primaire eindpunt
was globale respons (microbiologisch en klinisch) aan het eind van de IV-behandelperiode.
Merck Sharp & Dohme BV
Waarderweg 39 2031 BN Haarlem
Tel.: 0800-9999000
www.msd.nl
Mei 2012 (SmPC datum 19 juli 2012)
Verkorte productinformatie Mycamine® 50 mg/100 mg (augustus 2011)
Samenstelling: Mycamine® 50 mg/100 mg
poeder voor oplossing voor infusie
PFI_Ecalta_1BTekst.indd
1 (in natriumvorm). De toe te
dienen hoeveelheid na reconstitutie is 10 mg/ml en 20 mg/ml, resp. (in natriumvorm). Farmacotherapeutische
groep: Overige antimycotica voor systemisch gebruik, ATC-code: J02AX05. Therapeutische indicaties:
Volwassenen, adolescenten ≥ 16 jaar en ouderen: Behandeling van invasieve candidiasis; Behandeling van
oesofageale candidiasis bij patiënten voor wie intraveneuze therapie geschikt is; Profylaxe van Candida infectie
bij patiënten die allogene hematopoiëtische stamceltransplantatie ondergaan of van wie wordt verwacht
dat ze aan neutropenie lijden gedurende 10 dagen of langer. Kinderen (inclusief neonaten) en adolescenten
< 16 jaar: Behandeling van invasieve candidiasis; Profylaxe van Candida infectie bij patiënten die allogene
hematopoiëtische stamceltransplantatie ondergaan of van wie wordt verwacht dat ze aan neutropenie lijden
gedurende 10 dagen of langer. Bij de beslissing Mycamine te gebruiken dient rekening gehouden te worden
met het potentiële risico voor de ontwikkeling van levertumoren. Mycamine dient daarom uitsluitend te worden
gebruikt als andere antifungale middelen niet in aanmerking komen. Dosering en wijze van toediening:
Behandeling van invasieve candidiasis: 100 mg/dag, 2 mg/kg/dag bij een lichaamsgewicht < 40 kg. Als de patiënt
in onvoldoende mate reageert, bv. indien de kweken positief blijven of de klinische toestand niet verbetert, dan
mag de dosis worden verhoogd tot 200 mg/dag bij patiënten met een lichaamsgewicht > 40 kg of tot 4 mg/
kg/dag bij patiënten met een lichaamsgewicht ≤ 40 kg. Profylaxe van Candida infectie: 50 mg/dag, 1 mg/kg/
dag bij een lichaamsgewicht < 40 kg. Behandeling van oesofageale candidiasis: 150 mg/dag, 3 mg/kg/dag bij
een lichaamsgewicht < 40 kg. Contraindicaties: Overgevoeligheid voor het werkzame bestanddeel, voor andere
echinocandines of voor één van de hulpstoffen. Waarschuwingen en voorzorgen bij gebruik: De ontwikkeling
van foci van veranderde hepatocyten (FAH) en hepatocellulaire tumoren werd bij ratten waargenomen na
een behandelperiode van 3 maanden of langer. De leverfunctie dient zorgvuldig te worden gecontroleerd
tijdens behandeling met micafungine. Om het risico op adaptieve regeneratie en mogelijk daaropvolgende
levertumorvorming te minimaliseren, wordt vroegtijdig staken aanbevolen indien significante en persisterende
verhoging van ALT/AST optreedt. De micafungine behandeling dient uitgevoerd te worden na een zorgvuldige
risico/voordelen bepaling, met name bij patiënten met ernstige leverfunctiestoornissen of chronische
leverziekten die preneoplastische aandoeningen vertegenwoordigen, of bij het tegelijkertijd ondergaan van
een behandeling met hepatotoxische en/ of genotoxische eigenschappen. Er zijn onvoldoende gegevens
beschikbaar over de farmacokinetiek van micafungine bij patiënten met ernstige leverfunctiestoornis. Er kunnen
anafylactische/anafylactoïde reacties optreden, waarna de infusie met micafungine moet worden stopgezet
en de juiste behandeling moet worden ingesteld. Exfoliatieve huidreacties zijn gemeld; als patiënten uitslag
ontwikkelen, dienen zij nauwkeurig geobserveerd te worden. De therapie dient gestopt te worden als de laesies
verergeren. In zeldzame gevallen is er hemolyse gerapporteerd. In dit geval dient nauwlettend te worden gevolgd
of er geen verslechtering optreedt en er dient een risico/baten analyse gedaan te worden van voortzetting van
de therapie. Patiënten dienen nauwlettend te worden gecontroleerd op verslechtering van de nierfunctie.
Patiënten met zeldzame galactose intolerantie, Lapp lactasedeficiëntie of glucosegalactose malabsorptie dienen
dit middel niet te gebruiken. Interacties: Patiënten die Mycamine in combinatie met sirolimus, nifedipine of
itraconazol ontvangen, dienen te worden gecontroleerd op toxiciteit van sirolimus, nifedipine of itraconazol.
Gelijktijdige toediening van micafungine met amfotericine B-desoxycholaat is alleen toegestaan wanneer
de voordelen duidelijk opwegen tegen de risico’s, met een scherpe controle op mogelijke toxiciteit van
amfotericine B-desoxycholaat. Bijwerkingen: De volgende bijwerkingen deden zich vaak (≥ 1/100 tot < 1/10)
voor: leukopenie, neutropenie, anemie, hypokaliëmie, hypomagnesiëmie, hypocalciëmie, hoofdpijn, flebitis,
misselijkheid, braken, diarree, buikpijn, verhoogd bloedalkaline-fosfatase, verhoogd aspartaataminotransferase,
verhoogd alanineaminotransferase, verhoogd bilirubine in het bloed (inclusief hyperbilirubinemie), afwijkende
leverfunctietest, uitslag, pyrexie, koude rillingen. Naast bovengenoemde bijwerkingen zijn bij kinderen tevens
vaak thrombocytopenie, tachycardie, hypertensie, hypotensie, hyperbilirubinemie, hepatomegalie, acuut
nierfalen en verhoogd bloedureum gemeld. In de volledige SPC tekst worden de soms, zelden voorkomende
bijwerkingen en bijwerkingen die niet met de beschikbare gegevens kunnen worden bepaald gemeld.
Afleverstatus: UR. Overige productinformatie: Astellas Pharma B.V. Sylviusweg 62, 2333 BE Leiden. PO Box 344,
2300 AH Leiden. Tel: +31(0)71 545 57 45. Fax: +31(0)71 545 58 00.
Referenties: 1. number of patient days calculated from Kg sold ( Source: IMS Midas Kg sales- MAT 12 months sales
12/10) /Average daily dose over 14 days recommended treatment (Source:product SPC’s) 2. SmPC Mycamine
25042008
MYC2011-729
12.ECL.21.9
VERKORTE PRODUCTINFORMATIE
CANCIDAS® 50 mg poeder voor concentraat voor oplossing voor
intraveneuze infusie.
CANCIDAS® 70 mg poeder voor concentraat voor oplossing voor
intraveneuze infusie.
Samenstelling
CANCIDAS 50 mg bevat 50 mg caspofungin (als acetaat).
CANCIDAS 70 mg bevat 70 mg caspofungin (als acetaat).
Indicaties
• Behandeling van invasieve candidiasis bij volwassen patiënten
of kinderen.
• Behandeling van invasieve aspergillose bij volwassen patiënten of
kinderen die niet reageren op amfotericine B, toedieningsvormen van
amfotericine B met lipiden en/of itraconazol of deze niet verdragen.
• Empirische therapie voor vermoede schimmelinfecties (zoals
Candida of Aspergillus) bij volwassen patiënten of kinderen met
koorts en neutropenie.
Contra-indicaties
Overgevoeligheid voor het actieve bestanddeel of één van de hulpstoffen.
Waarschuwingen en voorzorgen
De werkzaamheid van caspofungine tegen de minder vaak
voorkomende niet-Candida-gisten en niet-Aspergillus-schimmels is
niet vastgesteld.
Bij gelijktijdig gebruik van CANCIDAS met ciclosporine werden geen
ernstige bijwerkingen aan de lever opgemerkt. Sommige gezonde
volwassen vrijwilligers die ciclosporine samen met caspofungine
kregen, vertoonden een voorbijgaande verhoging van het
alaninetransaminase (ALT) en aspartaattransaminase (AST) van minder
dan of gelijk aan 3 maal de bovenste waarde van het normale bereik
(ULN), die bij stopzetting van de behandeling verdween. CANCIDAS
kan gebruikt worden bij patiënten die ciclosporine krijgen als de
mogelijke voordelen opwegen tegen de potentiële risico’s. Zorgvuldige
controle van de leverenzymen moet worden overwogen als CANCIDAS
en ciclosporine gelijktijdig worden gebruikt.
Bij een matige leverfunctiestoornis wordt een verlaging van de
dagelijkse dosis naar 35 mg aanbevolen. Er is geen klinische ervaring
met ernstige leverinsufficiëntie of bij kinderen met elke mate van
leverinsufficiëntie. Te verwachten valt dat de blootstelling hoger is
dan bij matige leverinsufficiëntie; bij deze patiënten moet CANCIDAS
voorzichtig worden toegepast.
De gegevens over de veiligheid van een behandeling die langer duurt
dan 4 weken zijn beperkt.
Bijwerkingen
Volwassen patiënten
Flebitis was in alle patiëntpopulaties een vaak gemelde lokale bijwerking
op de injectieplaats. Andere lokale reacties waren erytheem, pijn/
gevoeligheid, jeuk, afscheiding, en een brandend gevoel.
De gemelde klinische en laboratoriumafwijkingen bij alle met
CANCIDAS behandelde volwassenen waren over het algemeen licht en
maakten zelden stopzetting noodzakelijk.
De volgende bijwerkingen zijn gemeld:
[Zeer vaak (≥1/10), Vaak (≥1/100 tot <1/10), Soms (≥1/1.000 tot <1/100)]
Vaak: verlaagd hemoglobine, verlaagd hematocriet, verminderd aantal
leukocyten, hypokaliëmie, hoofdpijn, flebitis, dyspnoe, misselijkheid,
diarree, braken, verhoogde leverwaarden (AST, ALT, alkalische
fosfatase, direct en totaal bilirubine), uitslag, pruritus, erytheem,
hyperhidrose, artralgie, koorts, rillingen, pruritus op infusieplaats.
Soms: anemie, trombocytopenie, coagulopathie, leukopenie, verhoogd
aantal eosinofielen, verminderd aantal trombocyten, verhoogd
aantal trombocyten, verminderd aantal lymfocyten, verhoogd
aantal leukocyten, verminderd aantal neutrofielen, vochtophoping,
hypomagnesiëmie, anorexia, gestoorde elektrolytenbalans,
hyperglykemie, hypocalciëmie, metabole acidose, angst, desoriëntatie,
slapeloosheid, duizeligheid, dysgeusie, paresthesie, slaperigheid,
tremoren, hypo-esthesie, oculaire icterus, wazig zien, oedeem van het
ooglid, verhoogde traanvorming, palpitaties, tachycardie, aritmieën,
atriumfibrilleren, hartfalen, tromboflebitis, flushing, opvliegers,
hypertensie, hypotensie, verstopte neus, faryngolaryngeale pijn,
tachypnoe, bronchospasmen, hoest, paroxysmale dyspnoe ‘s nachts,
2/4/13 11:01 AM
Netherlands Journal of Critical Care
Information for authors
The Netherlands Journal of Critical Care (Neth J Crit Care) is the official
journal of the Netherlands Society of Intensive Care (Nederlandse
Vereniging voor Intensive Care-NVIC). The journal has a circulation of
about 1,750 copies bimonthly in the Netherlands and Belgium.
High quality reports of research related to any aspect of intensive
care medicine, whether laboratory, clinical, or epidemiological,
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includes original articles, reviews, case reports, clinical images, book
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Describe the design of the study indicating, as appropriate, use of
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Summarize here accurately, although concisely, summarize how you
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main outcomes of the study.
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The conclusions and their applications (clinical or otherwise) should
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Articles should describe original investigations that have been
brought to an acceptable degree of completion. Articles should not
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The text of a case reports should also include an abstract,
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and laboratory findings, clinical course, response to treatment (if
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Article in journals: Calandra T, Cometta A. Anti­biotic therapy for
gram­­negative bacteremia. Infect Dis Clin North Am 1991;5:817-34
Books (-sections): Thijs LG. Fluid therapy in septic shock. In: Sibbald WJ,
Vincent J­L (eds). Clinical trials for the treatment of sepsis. (Update in
intensive care and emergency medicine, volume 19). Berlin Heidelberg
New York, Springer, 1995, pp 167-190. Conference Meetings: Rijneveld
AW, Lauw FN, te Velde AA, et al. The role of interferon­gamma in
murine pneumococcal pneumonia.
38th Interscience Conference on Antimicrobial Agents and
Chemotherapy (ICAAC). San Diego, Ca., 1998, pp 290
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the Netherlands Journal of Critical Care. Authors must disclose any
potential financial or ethical conflicts of interest regarding the contents
of the submission. Any relevant papers that may be considered as
duplicating in part the current submission should be reported.
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
35
Netherlands Journal of Critical Care
How to submit
Submit manuscript directly to: Editorial office e-mail:
[email protected]
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proofs must be returned within 48 hours of receipt.
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Authors review these changes at the proof stage but must limit their
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For guidelines on the NJCC’s house style see website
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initial capitals are not used in the title.
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36
N e th j cr it c ar e – vo lume 17 – n o 2 – may 2013
•Avoid “he” as a general pronoun. Make nouns and pronouns plural,
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e.g. (immuno) histology should be written as immunohistology and
histology, (un) sterile gloves as sterile or unsterile gloves.
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“Bij 98% werd technisch adequate wervelmorfometrie verricht”
becomes “In 98% spinal morphometry was technically successful.”
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the team has researched.
Table of abbreviations
AIDS
acquired immunodeficiency syndrome
ALI
acute lung injury
ARDS
adult respiratory distress syndrome
APACHE
acute phyisology and chronic health evaluation
BIPAP
biphasic positive airways pressure
CCU
coronary care unit
COPD
chronic obstructive pulmonary disease
CPAP
continuous positive airway pressure
CT
computerized or computed tomography
ECG
electrocardiogram
ECMO
extracorporeal membrane oxygenation
EEG
electroencephalogram
ELISA
enzyme-linked immunosorbent assay
ETCO2
end-tidal carbon dioxide
HDU
high dependency unit
HIV
human immunodeficiency virus
IC
intensive care
ICU
intensive care unit
IM
intramuscular
INR
international normalized ratio
IPPV
intermittent positive pressure ventilation
IV
intravenous
MAP
mean arterial pressure
MODS
multiorgan dysfunction syndrome
MRI
magnetic resonance imaging
PACU
post anaesthesia care unit
PEEP
postive end expiratory pressure
PET
positron emission tomography
SARS
severe adult respiratory syndrome
SIRS
systemic inflammatory response syndrome
SOFA
sequential or gan failure assessment
SPECT
single-photon emission ct
TIA
transient ischemic attack
TRALI
transfusion-related acute lung injury