LA CONSULTA SEMANAL

CONSULTA

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 Members.

Children's Hospital of Pittsburgh, Division of Critical Care Medicine, 15213, USA. carcilloj@anes.upmc.edu

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.

Publication Types:

Review

2: Crit Care  2002 Apr;6(2):113-6

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 Toronto, Canada.

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.

Publication Types:

Review

3: Curr Opin Infect Dis  2000 Jun;13(3):253-258

Improving the outcome of septic shock in children.

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 completo]

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 30912-3135, USA.

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.

Publication Types:

Review

5: Emerg Med J  2002 Mar;19(2):114-6

Choice of fluid for resuscitation of septic shock.

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 Sep;120(3):989-1002 [Texto completo]

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.

Publication Types:

Review

7: Intensive Care Med  2001;27 Suppl 1:S1-134

Guidelines for the management of severe sepsis and septic shock. The International Sepsis Forum.

Publication Types:

Guideline

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.

Publication Types:

Review

9: Scand J Infect Dis  2000;32(5):511-4

Plasmapheresis as part of the treatment for septic shock.

Hjorth V, Stenlund G.

Department of Anaesthesiology, Malarsjukhuset, Eskilstuna, Sweden.

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 septic shock.

Martin C, Viviand X, Leone M, Thirion X.

Intensive Care Department and Trauma Center, Nord Hospital, Marseilles University Hospital System, Marseilles School of Medicine, France.

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.

Publication Types:

Clinical Trial

11: Chest  2000 Jun;117(6):1749-54 [Texto completo]

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. pcmant@bpthosp.org

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.

Balk RA.

Department of Internal Medicine, Rush Medical College, Chicago, Illinois, USA. rbalk@rush.edu

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.

Publication Types:

Review

13: Crit Care Clin  2000 Apr;16(2):233-49

Pharmacologic issues in the management of septic shock.

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.

Publication Types:

Review

14: Eur J Anaesthesiol  2000 Jan;17(1):6-17

Haemodynamic management of a patient with septic shock.

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'.

Publication Types:

Review

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.

Publication Types:

Review