Garrett E. Foulke

Treatment of gram-negative bacteremia and septic shock with ha-1a human monoclonal antibody against endotoxin: A randomized, double-blind, placebo-controlled trial

BACKGROUND HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia. METHODS To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected. CONCLUSIONS HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

Treatment of Gram-Negative Bacteremia and Septic Shock with HA-1A Human Monoclonal Antibody against Endotoxin

BACKGROUND HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia. METHODS To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol. RESULTS Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected. CONCLUSIONS HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

Superiority of activated charcoal alone compared with ipecac and activated charcoal in the treatment of acute toxic ingestions

A prospective, randomized clinical trial compared the clinical effectiveness of syrup of ipecac and activated charcoal to that of activated charcoal alone in the treatment of acute toxic ingestions. Two hundred adult patients with mild to moderate oral overdoses were entered into the trial. Patients receiving only activated charcoal were discharged from the emergency department in significantly (P less than or equal to .05) less time than those receiving both syrup of ipecac and activated charcoal (6.0 +/- 0.3 vs 6.8 +/- 0.2 hours, respectively). The percentage of patients requiring nonpsychiatric hospitalizations was not significantly different between the two groups (11.2% vs 14.0%, respectively). For the hospitalized patients, the length of time spent in the ICU and in the hospital was not statistically different between the two groups. A complication rate of 5.4% was found with the ipecac and activated charcoal treatment compared with a 0.9% complication rate in the activated charcoal group (P less than or equal to .05). Three episodes of aspiration pneumonitis occurred after administration of ipecac and activated charcoal, while no episodes of aspiration were noted after treatment with only activated charcoal. Together, these data are consistent with the recommendation that ED treatment with activated charcoal alone be the gastrointestinal decontamination procedure of choice for the routine mildly-to-moderately orally poisoned adult patient.

Effective measures for reducing blood loss from diagnostic laboratory tests in intensive care unit patients

We studied ICU patient blood loss as a result of diagnostic testing (DBL) and the effect of two measures to reduce it. A policy of using small volumes (pediatric phlebotomy tubes, reduced syringe volumes) for the most frequent laboratory tests was implemented in our medical ICU. We prospectively studied 151 patients admitted during two consecutive 10-wk periods. During period 2, DBL was displayed on each ICU flow sheet. The DBL/day (43.6 +/- 3 [SEM] ml) was significantly lower (62.6 +/- 4 ml) than it would have been if standard volume tubes had been used. This represented an average savings of 33%. During period 1 (n = 81), eight (10%) patients with no diagnosis involving blood loss had a decrease in Hct and received transfusion. DBL was significantly higher (316 +/- 81 vs. 168 +/- 18 ml, p less than .001) for these patients and represented an average of 17% of transfusion requirements. During period 2 (n = 70), such transfusion requirements were significantly reduced (only one of 70, p less than .001), as were tests ordered/day (7.8 +/- 0.5 vs. 9.5 +/- 0.6, p less than .05). We conclude that DBL is a major health problem for the ICU patient. Routine use of small specimen volumes in this setting is warranted. Recording DBL for use in physician decision-making also significantly impacts this problem and should be considered an important part of the ICU database.

High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy

Study Objective. To assess the efficacy of high‐dose epinephrine (HDE) compared with standard‐dose epinephrine (SDE) in emergency department patients in cardiac arrest after SDE failed to improve asystole or ventricular fibrillation.

QRS interval in tricyclic antidepressant overdosage: Inaccuracy as a toxicity indicator in emergency settings

Emergency department treatment and disposition of tricyclic antidepressant (TCA)-overdose patients remains a common and difficult problem. Various clinical findings have been proposed as toxicity indicators. To study the performance of QRS duration as a predictor of toxicity in our patient population, we retrospectively reviewed the cases of all patients presenting to our ED with TCA overdosage. The charts of 102 patients with quantitative or qualitative laboratory confirmation of TCA ingestion were reviewed for ED findings and hospital course with specific attention to the occurrence of ventricular arrhythmias (VAs) or seizures. The ED ECG revealed that 57 patients had a maximal 12-lead ECG QRS interval duration (QRS) of less than .10 seconds (Group 1). The remaining 45 patients had QRS greater than or equal to .10 seconds (Group 2). Three patients (5%) in Group 1 and three (6%) in Group 2 experienced VAs. Four patients (7%) in Group 1 and five (11%) in Group 2 experienced seizures. There was no significant difference in the rate of occurrence of VAs or seizures between the two groups. Of note was the fact that five of eight VAs and nine of 11 seizures occurred in the ED setting. We conclude that determination of QRS duration is not an accurate indicator of VA or seizure risk for all TCA-overdose populations. In particular, risk of toxic events during the emergency phase of TCA overdose does not appear to be indicated by evaluation of the QRS duration in the ED.

Identifying toxicity risk early after antidepressant overdose

Despite the risk of life-threatening toxicities, care of most patients after antidepressant overdose (ADO) does not require the use of critical care resources. The use of emergency department (ED) clinical findings to identify ADO patients who subsequently manifested toxicity was evaluated prospectively. ADO risk assessment (ADORA) criteria included development of QRS interval > 0.10 seconds, arrhythmias, altered mental status, seizures, respiratory depression, or hypotension. Sixty-seven ADO patients were identified on presentation to a single ED and classified as low risk (LR, absence of criteria) or high risk (HR, presence of one or more criteria) based on development of criteria within 6 hours of ingestion (or ED presentation if ingestion time was not established). This system demonstrated 100% sensitivity in identifying study patients who developed significant toxicity problems. None of the 28 LR patients and 13 of 39 HR patients had subsequent complications (P < .01). No single clinical finding permitted risk classification. ADORA should identify patients who do not require further monitoring or other aggressive medical management for ADO.

Tricyclic antidepressant overdose: Emergency department findings as predictors of clinical course

There is controversy regarding the appropriate utilization of health care resources in the management of tricyclic antidepressant overdosage. Antidepressant overdose patients presenting to the emergency department (ED) are routinely admitted to intensive care units, but only a small proportion develop cardiac arrhythmias or other complications requiring such an environment. The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose. They found that major manifestations of toxicity on ED evaluation (altered mental status, seizures, arrhythmias, and conduction defects) were commonly associated with a complicated hospital course. Patients with the isolated findings of sinus tachycardia or QTc prolongation had no complications. No patient experienced a serious toxic event without major evidence of toxicity on ED evaluation and continued evidence of toxicity during the hospital course. These data support the concept that proper ED evaluation can identify a large body of patients with trivial ingestions who may not require hospital observation.

Clostridium difficile in the intensive care unit: management problems and prevention issues

Several patients hospitalized in our 12-bed medical ICU were found to have Clostridium difficile associated colitis. Stool cultures of all patients identified eight cases (three culture positive, and five culture and cytotoxin positive), seven of which were geographically and temporarily clustered within a 2-wk period. At least one patient appeared to contract the disease after hospitalization and in the absence of antibiotic therapy or other known major risk factors. The outbreak highlights the problem of C. difficile in the ICU. We believe that a heightened awareness of the multiple risk factors and preventive measures, along with consideration of possible nosocomial transmission, will be necessary to prevent or arrest future clusters of cases in the ICU. The diagnosis of one patient with this infection in a unit should prompt a review of all other patients within the unit.

Altitude-related illness

There are a number of conditions which can be grouped together as ARI. Many represent potentially fatal pathophysiological states that are rapidly reversible if identified and treated properly. Physiological alterations that result from the hypobaric hypoxia of altitude include cerebral vasodilatation, altered ventilatory patterns, pulmonary vasoconstriction, decreased cardiac output, and altered fluid and electrolyte balance. The various altitude-related illnesses represent a spectrum of conditions with overlapping presentations. The symptoms of AMS and HACE represent a continuum of disease that appears to be related to alterations in cerebrovascular autoregulation. High-altitude retinal hemorrhage may be related to similar vascular events in the retinal circulation. Although the etiology of HAPE remains unclear, it is likely that alterations of pulmonary vascular tone and flow play an important roles in its production. Knowledge regarding ARI is important in planning prophylaxis and instituting therapy. Gradual ascent and acclimatization are the mainstays of prophylaxis. Pharmacological prophylaxis is available for those who are prone to severe AMS. Prompt recognition, descent, and administration of oxygen constitute the major therapies for severe ARI. The ability to perform these three tasks can rapidly reverse a potentially fatal illness.