Ernest Benjamin

Treatment of Septic Shock with the Tumor Necrosis Factor Receptor:Fc Fusion Protein

BACKGROUNDnA recombinant, soluble fusion protein that is a dimer of an extracellular portion of the human tumor necrosis factor (TNF) receptor and the Fc portion of IgG1 (TNFR:Fc) binds and neutralizes TNF-alpha and prevents death in animal models of bacteremia and endotoxemia.nnnMETHODSnTo evaluate the safety and efficacy of TNFR:Fc in the treatment of septic shock, we conducted a randomized, double-blind, placebo-controlled, multicenter trial. A total of 141 patients were randomly assigned to receive either placebo or a single intravenous infusion of one of three doses of TNFR:Fc (0.15, 0.45, or 1.5 mg per kilogram of body weight). The primary end point was mortality from all causes at 28 days.nnnRESULTSnThere were 10 deaths among the 33 patients in the placebo group (30 percent mortality), 9 deaths among the 30 patients receiving the low dose of TNFR:Fc (30 percent mortality), 14 deaths among the 29 receiving the middle dose (48 percent mortality), and 26 deaths among the 49 receiving the high dose (53 percent mortality) (P = 0.02 for the dose-response relation). Baseline differences in the severity of illness did not account for the increased mortality in the groups receiving the higher doses of TNFR:Fc.nnnCONCLUSIONSnIn patients with septic shock, treatment with the TNFR:Fc fusion protein does not reduce mortality, and higher doses appear to be associated with increased mortality.

Multicenter evaluation of a human monoclonal antibody to Enterobacteriaceae common antigen in patients with Gram-negative sepsis.

ObjectiveTo evaluate in Gram-negative sepsis patients the human monoclonal immunoglobulin M antibody (MAB-T88) directed at the enterobacterial common antigen which is a specific surface antigen closely linked to lipopolysaccharide and shared by all members of the Enterobacteriaceae family of Gram-negative bacteria. DesignProspective, randomized, double-blinded, placebo-controlled, multicenter trial. SettingThirty-three academic medical centers in the United States. PatientsPatients were entered with a clinical diagnosis of sepsis, the presence of either shock or multiple organ dysfunction, and presumptive evidence for Gram-negative infection. InterventionsPatients received a single intravenous infusion, over 30 mins, of either 300 mg of MAB-T88 formulated in albumin, or placebo (albumin). Measurements and Main ResultsThe primary analysis group was prospectively identified as those patients with documented evidence of an infection with bacteria of the family Enterobacteriaceae at any site. The primary end point was survival within the first 28 days. A total of 826 patients were enrolled with 55% (n = 455) in the primary analysis group. There were no significant differences between the intervention and control primary analysis group study groups for sites of infection, severity of illness, underlying medical conditions, adequacy of antibiotic or surgical treatment, or other baseline variables except for a higher frequency of chronic renal failure in the MAB-T88 group (4.4% vs. 1.3%, p = .051). The average Acute Physiology and Chronic Health Evaluation II scores were 26.8 ± 8.6 (mean ± sd) in the MAB-T88-treated group and 26.5 ± 8.3 in the placebo-treated group (p = .72). There was no significant difference between MAB-T88- and placebo-treated groups during the first 28-day all-cause mortality in the primary analysis group (34.2% vs. 30.8%, p = .44) or in all 826 patients enrolled (37.0% vs. 34.0%, p = .36). On subset analysis, the use of MAB-T88 was not associated with significant mortality trends. More adverse events were seen with the use of MAB-T88 in the bacteremic enterobacterial common antigen group (p < .05). ConclusionsUse of the human monoclonal antibody, MAB-T88, did not improve the mortality in patients with presumed Gram-negative sepsis or in those patients with proven enterobacterial common antigen infections. No subset trends were identified that would support further investigation of this agent in sepsis.

A Prospective Emergency Department–Based Study of Pattern and Outcome of Neurologic and Neurosurgical Diseases in Haiti

OBJECTIVEnTo perform the first prospective survey of neurologic and neurosurgical emergency department (ED) admissions in Haiti.nnnMETHODSnData of all ED admissions at 3 Haitian hospitals for 90 consecutive days per site were collected prospectively. Patients who were given a diagnosis of a neurologic or neurosurgical disorder by the ED physician were entered in a deidentified database including demographics, presenting symptoms, brain imaging (when available), requests for neurosurgical consultation, and outcome.nnnRESULTSnOf the 7628 patients admitted to the ED during this study, 1243 patients had a neurologic disorder, yielding an ED-based neurologic disease prevalence of 16%. The 3 most common neurologic diseases were cerebrovascular disease (31%), neurotrauma (28%), and altered mental status (12%). Neurosurgical pathologies represented 19% of all neurologic admissions with a combined ED-based disease prevalence of 3%. Mortality rate was 9%. The most common neurosurgical disease was neurotrauma (87%), caused by motor vehicle accidents (59%), falls (20%), and assault (17%). Neurosurgical procedures were performed in 14 of 208 patients with a mortality rate of 33%.nnnCONCLUSIONSnThis prospective survey represents the first study of neurosurgical or neurologic disease patterns in Haiti. The results suggest specific disease priorities for this population that can guide efforts to improve Haitian health care and conduct more comprehensive epidemiologic studies in Haiti.

Utility of Ultrasound Versus Landmark-Guided Axillary Artery Cannulation for Hemodynamic Monitoring in the Intensive Care Unit:

Objectives. To assess the utility of ultrasound-guided axillary artery catheterization compared with anatomical landmark technique catheterization in the intensive care unit. Design. Randomized controlled trial. Setting. University hospital surgical and neurosurgical intensive care unit. Patients. A total of 33 critically ill patients undergoing arterial line placement. Interventions. Axillary arterial line placement under ultrasound guidance or by using anatomical landmarks. Measurements and main results. Procedure duration, number of attempts (skin punctures), needle repositionings, and aborted procedures were compared. A total of 33 patients were randomly assigned to either the ultrasound group (n = 18) or the anatomical landmark group (n = 15). Aborted procedures were significantly greater in the landmark group (n = 4) than in the ultrasound group (n = 0); P = .019. Procedure duration (mean ± SD) in the ultrasound group was 7.01 ± 4.40 minutes compared with 9.29 ± 10.00 minutes in the landmark group; ...

Shifting Pneumothorax A Radiographic and Sonographic Evaluation

A 62-year-old woman was admitted for elective bilateral nephrectomies for symptomatic large bilateral polycystic kidneys. In the immediate postoperative period, the patient was hypotensive requirin...

Critical Conversations Procedure Centers and the Role in Safety, Throughput, Training, and Access to Services

VignetteA 36-year-old homeless man was brought in to the emergency room with altered mental status and was unable to give a history. Based on prior emergency visits, he has a history of IV drug abuse and alcohol abuse. His vital signs on arrival are the following: HR of 110 (regular), BP of 102/58, temperature of 98.0, and respiratory rate of 8/min. His Glasgow Coma Scale score is 7. Physical examination results are that he is grossly obtunded, responds only to deep painful stimuli, is nonverbal, and moves all extremities. Pupils are small, 2 to 3 mm, and reactive. His heart reveals regular tachycardia. Lungs are clear to auscultation. Abdomen is within normal limits. His extremities are warm to touch. Skin reveals ecchymosis. His initial head CT finding is negative for bleeding, infarct, or mass. He has severe metabolic acidosis, and the urine toxin screen result is positive for cocaine and opiates. His creatinine kinase enzyme is greater than 20,000 IU/L. Peripheral venous access attempts are unsuccessf...