Efficacy and safety of recombinant human activated protein C for severe sepsis.

BACKGROUND: Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 microg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C. RESULTS: A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06). CONCLUSIONS: Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.

Small bowel necrosis associated with early postoperative jejunal tube feeding in a trauma patient.

Several investigators have reported the association of small bowel ischemia and necrosis with needle catheter jejunostomy. We report a case of small bowel necrosis with continuous jejunal tube feeding and review the pathogenesis implicated in feeding-induced bowel necrosis.

Blood glucose and neurologic outcome with global brain ischemia.

OBJECTIVE: To investigate the relationship between neurologic outcome and blood glucose concentrations in survivors of cardiopulmonary arrest. DESIGN: Retrospective case series chart review. SETTING: Adult multidisciplinary intensive care unit (ICU) of a tertiary referral medical center. SUBJECTS: Consecutive patients over a 12-month period surviving cardiopulmonary resuscitation (CPR). INTERVENTIONS: Variables that were examined that could affect the relationship between the circulating glucose concentration and neurologic outcome included: location of arrest (inhospital/out-of-hospital), age, history of diabetes mellitus, duration of arrest, CPR duration, initial cardiac rhythm, and drugs administered during arrest. Cerebral recovery was evaluated by a 5-point outcome scale (Glasgow Pittsburgh Brain Stem Score) on ICU admission, and 24 and 48 hrs after ICU admission. MEASUREMENTS AND MAIN RESULTS: Observations were made on 85 patients, of whom 67% had inpatient CPR and 33% received out-of-hospital CPR. The duration of arrest of 66 (78%) patients was <5 mins. Mean CPR duration was 13.7 mins. Twenty-one percent of patients had diabetes. The mean blood glucose concentration post-CPR (n = 80) was 272 mg/dL (15.1 mmol/L). A statistically significant association was shown between high glucose concentration post-CPR and severe cerebral outcome among a small subset of patients with CPR lasting >5 min. CONCLUSIONS: The present study does not support an association between the concentration of glucose post-CPR and neurologic outcome. The previously reported casual relationship between hyperglycemia and neurologic prognosis may be an epiphenomenon of the severity of global cerebral ischemia in humans.

Therapeutic impact of pulmonary artery catheterization in a medical/surgical ICU.

The objective of this study was to determine the following: (1) if standard clinical evaluation is sufficient to provide an accurate estimate of hemodynamic status of unstable ICU patients; (2) the impact of pulmonary artery catheterization (PAC) on diagnosis and treatment plan; and (3) whether therapy provided after PAC was appropriate as judged by an expert panel of senior ICU physicians. A descriptive analysis of utilization of pulmonary artery catheters in a medical/surgical ICU population was performed in a university-affiliated hospital (24-bed medical/surgical ICU). The subjects included 154 medical/surgical patients judged by ICU residents and attendings to require PAC. All 154 patients underwent PAC with four patients having more than one catheterization. Prior to insertion of the catheter, a questionnaire was completed by medical/surgical residents and attendings indicating reasons for PAC insertion and estimate of hemodynamics. Following PAC, residents/attendings indicated their evaluation of hemodynamics and planned therapy. An expert panel rated performance of the house staff regarding treatment plan on a scale of 1 to 5 (5 indicating optimal therapy). The overall proportion correct classification for pulmonary artery wedge pressure (PAWP), CO, and systemic vascular resistance (SVR) were 47 percent, 51 percent, and 36 percent, respectively. In 45 percent of PAC, information obtained resulted in a major change in therapy. Major change in therapy occurred more often when prediction of PAWP by residents proved inaccurate. The expert panel judged appropriate scores of 3, 4 and 5 in 84 percent of the cases. Prediction of hemodynamics in ICU patients by clinical evaluation alone is inaccurate and unreliable. There is a positive correlation between inaccurate prediction of hemodynamics and major therapeutic changes after PAC. Most resident/attending performance was judged appropriate. Results of this study suggest that PAC was instrumental to the management scheme in many patients unresponsive to initial therapy. However, a subset of ICU patients were judged to have been managed favorably, yet had treatment based on inaccurate hemodynamic assessment.

Clinical assessment of hemodynamic values in two surgical intensive care units. Effects on therapy.

A prospective study of 126 surgical patients from two institutions was undertaken to assess the impact of pulmonary artery catheterization in surgical intensive care units. Before catheterization, surgical residents were asked to predict pulmonary artery wedge pressure, cardiac output, systemic vascular resistance, and plan of therapy. After catheterization, each chart was reviewed by a panel of intensive care specialists and a general surgeon. Correct classification for the hemodynamic variables ranged from 47% to 55%. Catheterization results prompted a major change in therapy in 50% of patients. The data suggest that hemodynamic variables obtained from pulmonary artery catheterization improve the accuracy of bedside evaluation and lead to alteration in therapy, particularly in patients whose pulmonary artery wedge pressure predictions were poor.

Amniotic fluid embolism associated with castor oil ingestion.

We report a case of an amniotic fluid embolism (AFE) causing a cardiorespiratory arrest associated temporally with ingestion of castor oil in a full-term normal pregnancy. Risk factors usually associated with AFE were not found in this patient.

A method for predicting survival and mortality of ICU patients using objectively derived weights.

Data at ICU admission and after 24 h in the ICU were collected on 755 patients, to derive multiple logistic regression models for predicting hospital mortality. The derived models contained relatively few and easily obtained variables. The weight associated with each variable was determined objectively. There were seven admission variables, none of which were treatment dependent, and seven 24-h variables reflecting treatments and patients' conditions in the ICU. Predicted outcomes using these two models were closely correlated with actual outcome. Theoretically, a predictive model would be useful to physicians for triage decisions as well as determining aggressiveness of care through discussions with families, determining utilization of ICU facilities, and objectively comparing different ICUs. This research represents an initial attempt to develop models that are not based on subjectively determined weights.