1: Crit Care Med 2002 Jun;30(6):1365-78
Clinical practice parameters for hemodynamic
support of pediatric and neonatal patients in septic shock.
Carcillo JA, Fields AI;
American College of Critical Care Medicine Task Force Committee
Children's Hospital of Pittsburgh, Division of
Critical Care Medicine, 15213, USA. firstname.lastname@example.org
BACKGROUND: The Institute of Medicine has called
for the development of clinical guidelines and practice parameters to
develop "best practice" and potentially improve patient outcome.
OBJECTIVE: To provide American College of Critical Care Medicine clinical
guidelines for hemodynamic support of neonates and children with septic
shock. SETTING: Individual members of the Society of Critical Care
Medicine with special interest in neonatal and pediatric septic shock were
identified from literature review and general solicitation at Society of
Critical Care Medicine Educational and Scientific Symposia (1998-2001).
METHODS: The MEDLINE literature database was searched with the following
age-specific keywords: sepsis, septicemia, septic shock, endotoxemia,
persistent pulmonary hypertension, nitric oxide, and extracorporeal
membrane oxygenation. More than 30 experts graded literature and drafted
specific recommendations by using a modified Delphi method. More than 30
more experts then reviewed the compiled recommendations. The task-force
chairman modified the document until <10% of experts disagreed with the
recommendations. RESULTS: Only four randomized controlled trials in
children with septic shock could be identified. None of these randomized
trials led to a change in practice. Clinical practice has been based, for
the most part, on physiologic experiments, case series, and cohort studies.
Despite relatively low American College of Critical Care Medicine-graded
evidence in the pediatric literature, outcomes in children have improved
from 97% mortality in the 1960s to 60% in the 1980s and 9% mortality in
1999. U.S. hospital survival was three-fold better in children compared
with adults (9% vs. 27% mortality) in 1999. Shock pathophysiology and
response to therapies is age specific. For example, cardiac failure is a
predominant cause of death in neonates and children, but vascular failure
is a predominant cause of death in adults. Inotropes, vasodilators (children),
inhaled nitric oxide (neonates), and extracorporeal membrane oxygenation
can be more important contributors to survival in the pediatric
populations, whereas vasopressors can be more important contributors to
adult survival. CONCLUSION: American College of Critical Care Medicine
adult guidelines for hemodynamic support of septic shock have little
application to the management of pediatric or neonatal septic shock.
Studies are required to determine whether American College of Critical
Care Medicine guidelines for hemodynamic support of pediatric and neonatal
septic shock will be implemented and associated with improved outcome.
2: Crit Care
Pro/con clinical debate: are steroids useful
in the management of patients with septic shock?
Ritacca FV, Simone C, Wax R, Craig KG, Walley KR.
Resident, Department of Medicine, University of
Decision-making in the intensive care unit is
often very difficult. Although we are encouraged to make evidence-based
decisions, this may be difficult for a number of reasons. To begin with,
evidence may not exist to answer the clinical question. Second, when there
is evidence it may not be applicable to the patient in question or the
clinician may be reluctant to apply it to the patient based on a number of
secondary issues such as costs, premorbid condition or possible
complications. Finally, emotions are often highly charged when caring for
patients that have a significant chance of death, and care-givers as well
as families are frequently prepared to take chances on a therapy whose
benefit is not entirely clear. Steroid use in septic shock is an example
of a therapy that makes some sense but has conflicting support in the
literature. In this issue of Critical Care Forum, the two sides of this
often heated debate are brought to the forefront in an interesting format.
3: Curr Opin Infect Dis
Improving the outcome of septic shock in
Kirsch EA, Giroir BP.
aDepartment of Pediatrics,Wilford Hall Medical
Center, Lackland AFB, Texas, USA and bDepartment of Pediatrics, University
of Texas Southwestern Medical Center, Dallas, Texas, USA.
Sepsis is an important cause of pediatric
morbidity and mortality. Improving the outcome of pediatric sepsis
requires diverse efforts, including prevention, early recognition,
improvements in early management and transport, and physiology-directed
care. Awareness that septic shock represents a pathophysiologic host
response to infection has prompted investigation of immune mediators and
coagulation factors as potential targets for anti-sepsis therapies.
Advancements thus far include: the potential prevention of neonatal sepsis
with granulocyte colony-stimulating factor; recognition of clindamycin as
a potential inhibitor of endotoxin release; improved outcome from
meningococcal disease in children treated with bactericidal/permeability-increasing
protein (rBPI21); and improved outcome from sepsis in premature infants
treated with pentoxifylline. Further randomized controlled studies of
immunomodulatory agents are indicated and a few are in progress. Current
studies on genetic propensities in cytokine and coagulation protein
expression may explain variability in patient outcomes and eventually lead
to genomics-based therapeutics.
4: Postgrad Med 2002 Mar;111(3):53-6, 59-60, 63-4 passim [Texto
Optimal management of septic shock. Rapid
recognition and institution of therapy are crucial.
Fitch SJ, Gossage JR.
Multidisciplinary Intensive Care Unit, Section
of Pulmonary and Critical Care Medicine, Department of Medicine, Medical
College of Georgia School of Medicine, BBR-5513, 1120 15th St, Augusta, GA
Septic shock is a common problem in hospitalized
patients. Optimal management depends on rapid recognition, aggressive
restoration of circulating volume with fluid boluses, initiation of
appropriate antibiotic therapy, implementation of adequate monitoring, and
meticulous attention to the details of care. Mean arterial pressure should
be increased to between 65 and 75 mm Hg as soon as possible to reduce the
likelihood of multiorgan dysfunction. Despite these therapeutic maneuvers,
however, mortality rates are likely to remain high until the development
of therapies that better target the underlying mechanisms of sepsis.
5: Emerg Med J
Choice of fluid for resuscitation of septic
Sparrow A, Hedderley T, Nadel S.
Paediatric Intensive Care Unit, Department of
Paediatrics, St Mary's Hospital, London, UK.
OBJECTIVES: To determine current practice in
choice of fluid resuscitation in children following publication of a
systematic review that demonstrated a higher mortality in patients treated
with human albumin solution. METHODS: A descriptive telephone and postal
questionnaire survey directed at the on call paediatric registrar, lead
clinician for paediatrics and the paediatric pharmacist at each of 33
hospitals within the Greater London area. The study was coordinated by the
Paediatric Intensive Care Unit at St Mary's Hospital, London. The
questionnaire was designed to assess whether a protocol/guidelines existed
for resuscitation fluid in children with septic shock; whether the
participants were aware of the systematic review and if so, had it changed
clinical practice. The word "protocol" was used in its broadest
sense to include guideline and policy. RESULTS: 11 hospitals had
guidelines for fluid resuscitation of septic shock in children. These
varied greatly: only three gave clear instructions of which fluid to use
and how to use it. Choice of fluid varied widely and there was wide
discrepancy between consultant's and registrar's choice of fluid. The
systematic review had lead to a change in policy in two thirds of
respondents. CONCLUSION: It is apparent that few paediatric departments
have a written protocol or guidelines for the management of septic shock
that is accessible to all those concerned in the acute treatment of
seriously ill children. The systematic review into choice of fluid has had
an impact on clinical practice with no data regarding whether this is in
the patient's best interests.
6: Chest 2001
Physiology of vasopressin relevant to
management of septic shock.
Holmes CL, Patel BM, Russell JA, Walley KR.
University of British Columbia Program of
Critical Care Medicine and the McDonald Research Laboratories, St. Paul's
Hospital, Vancouver, British Columbia, Canada.
Vasopressin is emerging as a rational therapy
for the hemodynamic support of septic shock and vasodilatory shock due to
systemic inflammatory response syndrome. The goal of this review is to
understand the physiology of vasopressin relevant to septic shock in order
to maximize its safety and efficacy in clinical trials and in subsequent
therapeutic use. Vasopressin is both a vasopressor and an antidiuretic
hormone. It also has hemostatic, GI, and thermoregulatory effects, and is
an adrenocorticotropic hormone secretagogue. Vasopressin is released from
the axonal terminals of magnocellular neurons in the hypothalamus.
Vasopressin mediates vasoconstriction via V1-receptor activation on
vascular smooth muscle and mediates its antidiuretic effect via
V2-receptor activation in the renal collecting duct system. In addition,
vasopressin, at low plasma concentrations, mediates vasodilation in
coronary, cerebral, and pulmonary arterial circulations. Septic shock
causes first a transient early increase in blood vasopressin
concentrations that decrease later in septic shock to very low levels
compared to other causes of hypotension. Vasopressin infusion of 0.01 to
0.04 U/min in patients with septic shock increases plasma vasopressin
levels to those observed in patients with hypotension from other causes,
such as cardiogenic shock. Increased vasopressin levels are associated
with a lesser need for other vasopressors. Urinary output may increase,
and pulmonary vascular resistance may decrease. Infusions of > 0.04 U/min
may lead to adverse, likely vasoconstriction-mediated events. Because
clinical studies have been relatively small, focused on physiologic end
points, and because of potential adverse effects of vasopressin, clinical
use of vasopressin should await a randomized controlled trial of its
effects on clinical outcomes such as organ failure and mortality.
7: Intensive Care Med 2001;27 Suppl 1:S1-134
Guidelines for the management of severe
sepsis and septic shock. The International Sepsis Forum.
8: Paediatr Drugs 2001;3(1):9-27
Management of sepsis and septic shock in
infants and children.
von Rosenstiel N, von Rosenstiel I, Adam D.
University Children's Hospital, Munich, Germany.
Sepsis and septic shock constitute an important
cause of morbidity and mortality in critically ill children. Thus, the
systemic response to infection and its management remains a major
challenge in clinical medicine. Apart from antibiotic administration, the
majority of available therapies are limited to supportive strategies,
although considerable efforts are being undertaken to devise innovative
approaches that modulate host inflammatory responses. In suspected sepsis,
2 or 3 days' empiric antibiotic therapy should begin immediately after
cultures have been obtained without awaiting results. Antibiotics should
be re-evaluated when the results of the cultures and susceptibility tests
are available. The initial antibiotic (combination) is determined by the
likely causative agent, susceptibility patterns within a specific
institution, CNS penetration, toxicity, and the patient's hepatic and
renal function. The likely offending micro-organism in turn depends
primarily on the patient's age, coexistence of any premorbid condition
leading to impaired immune response, and the presenting signs and symptoms.
Close attention to cardiovascular, respiratory, fluid and electrolyte,
haematological, renal and metabolic/nutritional support is essential to
optimise outcome. Fluid resuscitation is of utmost importance to overcome
hypovolaemia on the basis of a diffuse capillary leak. Monitoring and
normalisation of the heart rate is essential. In case of nonresponse to
fluid resuscitation, inotropic and vasoactive agents are commonly used to
increase cardiac output, maintain adequate blood pressure and enhance
oxygen delivery to the tissue. Because respiratory distress syndrome is
seen in about 40% of critically ill children with septic shock, increased
inspired oxygen is essential. To provide optimal relief from respiratory
muscle fatigue and facilitate the provision of positive airway pressure,
early intubation and mechanical ventilation should be considered. Renal
support is essential to avoid prolonged renal shutdown in hypoperfusion
states. Haematological support comprises replacement therapy of clotting
factors to overcome disseminated intravascular coagulation. Metabolic
support may include glucose support, extraction of ammonia from the body
and recognition of liver dysfunction. Nutritional support may modify the
inflammatory host response, and early enteral feeding can improve outcome
in critical illness. To date, glucocorticoid and non-glucocorticoid anti-inflammatory
agents have not shown significant benefit in septic patients.
9: Scand J Infect Dis 2000;32(5):511-4
Plasmapheresis as part of the treatment for
Hjorth V, Stenlund G.
Department of Anaesthesiology, Malarsjukhuset,
Plasmapheresis is one of the methods which has
been tried in the effort to influence the course of severe sepsis with
septic shock and to improve survival rates. This is a retrospective study
of 17 consecutive patients with septic shock who were treated with acute
plasmapheresis. Nine out of 16 patients with verified etiology suffered
from infections with Gram-positive bacteria. Three (18%) of the treated
patients died. The estimated mortality rate based on the patients' initial
APACHE II scores was 62%. No serious side-effects of treatment were
observed. This study indicates that plasmapheresis is a safe treatment for
patients with septic shock and has a positive effect on survival.
Prospective, randomized studies would be valuable to determine the role of
plasmapheresis in the management of patients with septic shock.
10: Crit Care Med 2000 Aug;28(8):2758-65
Effect of norepinephrine on the outcome of
Martin C, Viviand X, Leone M, Thirion X.
Intensive Care Department and Trauma Center,
Nord Hospital, Marseilles University Hospital System, Marseilles School of
OBJECTIVE: Despite increasingly sophisticated
critical care, the mortality of septic shock remains elevated. Accordingly,
care remains supportive. Volume resuscitation combined with vasopressor
support remains the standard of care as adjuvant therapy, and many
consider dopamine to be the pressor of choice. Because of fear of
excessive vasoconstriction, norepinephrine is considered to be deleterious.
The present study was designed to identify factors associated with outcome
in a cohort of septic shock patients. Special attention was paid to
hemodynamic management and to the choice of vasopressor used, to determine
whether the use of norepinephrine was associated with increased mortality.
DESIGN: Prospective, observational, cohort study. SETTING: Intensive care
unit of a university hospital. PATIENTS: Ninety-seven adult patients with
septic shock. MEASUREMENTS AND MAIN RESULTS: Data from these patients were
examined to select variables independently and significantly associated
with outcome during the hospital stay. Nineteen clinical, biological, and
hemodynamic variables were collected at study entry or during the first
48-72 hrs and analyzed for each patient. A stepwise logistic regression
analysis and a model building strategy were used to identify variables
independently and significantly associated with outcome. The overall
hospital mortality was 73% (71 patients). Five variables were
significantly associated with outcome. One factor was strongly associated
with a favorable outcome: the use of norepinephrine as part of the
hemodynamic support of the patients. The 57 patients who were treated with
norepinephrine had significantly lower hospital mortality (62% vs. 82%, p
< .001; relative risk = 0.68; 95% confidence interval = 0.54-0.87) than
the 40 patients treated with vasopressors other than norepinephrine (high-dose
dopamine and/or epinephrine). Four variables were associated with a poor
outcome and significantly higher hospital mortality: pneumonia as a cause
of septic shock (82% vs. 61%, p < .03; relative risk = 1.47; 95%
confidence interval = 1.07-1.77), organ system failure index < or = 3
(92% vs. 60%, p < .001; relative risk = 1.47; 95% confidence interval =
1.17-1.82), low urine output at entry to the study (88% vs. 60%, p <
.01; relative risk = 1.44; 95% confidence interval = 1.06-1.87), and
admission blood lactate concentration > 4 mmol/L (91% vs. 63%, p <
.01; relative risk = 1.60; 95% confidence interval = 1.27-1.84).
CONCLUSIONS: Our results indicate that the use of norepinephrine as part
of hemodynamic management may influence outcome favorably in septic shock
patients. The data contradict the notion that norepinephrine potentiates
end-organ hypoperfusion, thereby contributing to increased mortality.
However, the present study suffers from some limitation because of its
nonrandomized, open-label, observational design. Hence, a randomized
clinical trial is needed to clearly establish that norepinephrine improves
mortality of patients with septic shock, as compared with high-dose
dopamine or epinephrine. Pneumonia as the cause of septic shock, high
blood lactate concentration, and low urine output on admission are strong
indicators of a poor prognosis. Multiple organ failure is confirmed as a
reliable predictor of mortality in septic patients.
11: Chest 2000
Negative fluid balance predicts survival in
patients with septic shock: a retrospective pilot study.
Alsous F, Khamiees M, DeGirolamo A, Amoateng-Adjepong
Y, Manthous CA.
Division of Pulmonary and Critical Care,
Bridgeport Hospital and Yale University School of Medicine, Bridgeport, CT
06610, USA. email@example.com
OBJECTIVE: We hypothesized that patients with
septic shock who achieve negative fluid balance (< or =-500 mL) on any
day in the first 3 days of management are more likely to survive than
those who do not. DESIGN: Retrospective chart review. PATIENTS: Thirty-six
patients admitted with the diagnosis of septic shock. SETTING: Twelve-bed
medical ICU of a 300-bed community teaching hospital. METHODS: Medical
records of 36 patients admitted to our medical ICU over a 21-month period
were examined. Patients with septic shock who required dialysis prior to
hospitalization were not included. A number of demographic and physiologic
variables were extracted from the medical records. Admission APACHE (acute
physiology and chronic health evaluation) II and daily sequential organ
failure assessment (SOFA) scores were computed from the extracted data.
Variables were compared between survivors and nonsurvivors and in patients
who did vs those who did not achieve negative (< or = 500 mL) fluid
balance in > or = 1 day of the first 3 days of management. Survival
risk ratios (RRs) were used as the measure of association between negative
fluid balance and survival. RRs were adjusted for age, APACHE II scores,
SOFA scores on the first and third days, and the need for mechanical
ventilation, by stratified analyses. RESULTS: Patients ranged in age from
16 to 85 years with a mean (+/- SE) age of 67.4 +/- 3.3 years. The mean
admission APACHE II score was 25.4 +/- 1.4, and the day 1 SOFA score was
9.0 +/- 0.8. Twenty patients did not survive; nonsurvivors had higher mean
APACHE II scores than survivors (29.8 vs 20.4, respectively) and higher
first day SOFA scores than survivors (10.8 vs 6.9, respectively), and they
were more likely to require vasopressors and mechanical ventilation
compared to patients who survived. Whereas all 11 patients who achieved a
negative balance of > 500 mL on > or = 1 of the first 3 days of
treatment survived, only 5 of 25 patient who failed to achieve a negative
fluid balance of > 500 mL by the third day of treatment survived (RR,
5.0; 95% CI, 2.3 to 10.9; p = 0.00001). At least 1 day of net negative
fluid balance in the first 3 days of treatment strongly predicted survival
across the strata of age, APACHE II scores, first- and third-day SOFA
scores, the need for mechanical ventilation, and creatinine levels
measured at admission. CONCLUSION: These results suggest that at least 1
day of negative fluid balance (< or = -500 mL) achieved by the third
day of treatment may be a good independent predictor of survival in
patients with septic shock. These findings suggest the hypothesis "that
negative fluid balance achieved in any of the first 3 days of septic shock
portends a good prognosis," for a larger prospective cohort study.
12: Crit Care Clin 2000 Apr;16(2):337-52, vii
Pathogenesis and management of multiple organ
dysfunction or failure in severe sepsis and septic shock.
Department of Internal Medicine, Rush Medical
College, Chicago, Illinois, USA. firstname.lastname@example.org
Organ system dysfunction is a common adverse
sequelae of severe sepsis and septic shock and has been reported to be the
most common cause of death in the noncoronary intensive care unit. The
pathophysiology of the development of multiple organ system dysfunction is
likely multifactoral and may take several different pathways. The
frequency of specific organ system involvement is dependent on the
definition used to describe the organ dysfunction. The presence of organ
dysfunction has great clinical impact on the underlying disease process,
can prolong the hospital stay, increase the cost of care, and has been
associated with an increase in mortality rate. At present, there is no
recognized specific treatment for established organ failure, this primary
attention has been directed toward prevention.
13: Crit Care Clin 2000 Apr;16(2):233-49
Pharmacologic issues in the management of
Jindal N, Hollenberg SM, Dellinger RP.
Department of Medicine, Rush Medical College,
Chicago, Illinois, USA.
Despite our increased understanding of the
biochemistry and physiology of sepsis, the treatment of septic shock
remains a challenge. Initial management of septic shock entails urgent and
emergent stabilization of the patient followed by broad-spectrum, empiric
antibiotic therapy. After volume resuscitation, vasopressors or inotropic
therapy or both may be necessary to restore perfusion. Adjunctive
therapies and monitoring strategies may be helpful in preventing
complications in the intensive care setting. Additional research and
clinical trials are needed to identify supportive interventions that may
affect the outcome of the septic patient.
14: Eur J Anaesthesiol
Haemodynamic management of a patient with
Reinhart K, Sakka SG, Meier-Hellmann A.
Department of Anaesthesiology and Intensive Care
Medicine, Friedrich-Schiller-University, Jena, Germany.
For supportive therapy in sepsis, an adequate
volume loading is likely the first step, and possibly the most important
step in the treatment of patients with septic shock. However, it is still
a matter of debate what kind of fluids, endpoints for resuscitation and
monitoring techniques should be used. Nevertheless, therapies which
closely control volume loading and regional perfusion are becoming more
utilized. An elevated global O2-supply (DO2) may be necessary and
beneficial in most of these patients but the increase of DO2 should be
guided by the measurement of parameters assessing global and regional
oxygenation. Routine strategies for elevating DO2 by the use of very high
dosages of catecholamines cannot be recommended. Vasopressors should be
used to achieve an adequate perfusion pressure. With norepinephrine, no
negative effects on regional perfusion have been demonstrated when the
patient is adequately volume resuscitated and the DO2 is normal or even
slightly elevated. In contrast, epinephrine should be avoided because it
seems to redistribute blood flow away from the splanchnic region. There is
controversy whether dopamine should still be used as a first-line drug in
patients with septic shock, because there are some clinical and
experimental data that indicate unfavourable effects on mucosal perfusion
of the gut. To date, there are no convincing data to support the routine
use of low-dose dopamine or dopexamine in patients with sepsis. Neither
low-dose dopamine nor dopexamine have been proven to prevent renal failure
in septic patients. Furthermore, there is evidence that low-dose dopamine
may reduce mucosal perfusion in the gut in some patients. Dopexamine has
been suggested to improve splanchnic perfusion but because these effects
remain somewhat controversial, there is as yet no reason for a general
recommendation for dopexamine in septic patients. These recommendations
are currently limited by the lack of sufficient outcome studies and
studies which evaluate regional perfusion. Until the various catecholamine
regimes are more fully examined, recommendations for catecholamine support
in sepsis must be considered 'conditional'.
15: Crit Care Med 1999 Feb;27(2):231-2
Mechanisms and management of myocardial
dysfunction in septic shock.
Carpati CM, Astiz ME, Rackow EC.