Gerard Fulda

Human Polymerized Hemoglobin for the Treatment of Hemorrhagic Shock when Blood Is Unavailable: The USA Multicenter Trial

BACKGROUND Human polymerized hemoglobin (PolyHeme, Northfield Laboratories) is a universally compatible oxygen carrier developed to treat life-threatening anemia. This multicenter phase III trial was the first US study to assess survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. STUDY DESIGN Injured patients with a systolic blood pressure</=90 mmHg were randomized to receive field resuscitation with PolyHeme or crystalloid. Study patients continued to receive up to 6 U of PolyHeme during the first 12 hours postinjury before receiving blood. Control patients received blood on arrival in the trauma center. This trial was conducted as a dual superiority/noninferiority primary end point. RESULTS Seven hundred fourteen patients were enrolled at 29 urban Level I trauma centers (79% men; mean age 37.1 years). Injury mechanism was blunt trauma in 48%, and median transport time was 26 minutes. There was no significant difference between day 30 mortality in the as-randomized (13.4% PolyHeme versus 9.6% control) or per-protocol (11.1% PolyHeme versus 9.3% control) cohorts. Allogeneic blood use was lower in the PolyHeme group (68% versus 50% in the first 12 hours). The incidence of multiple organ failure was similar (7.4% PolyHeme versus 5.5% control). Adverse events (93% versus 88%; p=0.04) and serious adverse events (40% versus 35%; p=0.12), as anticipated, were frequent in the PolyHeme and control groups, respectively. Although myocardial infarction was reported by the investigators more frequently in the PolyHeme group (3% PolyHeme versus 1% control), a blinded committee of experts reviewed records of all enrolled patients and found no discernable difference between groups. CONCLUSIONS Patients resuscitated with PolyHeme, without stored blood for up to 6 U in 12 hours postinjury, had outcomes comparable with those for the standard of care. Although there were more adverse events in the PolyHeme group, the benefit-to-risk ratio of PolyHeme is favorable when blood is needed but not available.

The circulatory-respiratory determination of death in organ donation

Objective:Death statutes permit physicians to declare death on the basis of irreversible cessation of circulatory–respiratory or brain functions. The growing practice of organ donation after circulatory determination of death now requires physicians to exercise greater specificity in circulatory–respiratory death determination. We studied circulatory–respiratory death determination to clarify its concept, practice, and application to innovative circulatory determination of death protocols. Results:It is ethically and legally appropriate to procure organs when permanent cessation (will not return) of circulation and respiration has occurred but before irreversible cessation (cannot return) has occurred because permanent cessation: 1) is an established medical practice standard for determining death; 2) is the meaning of “irreversible” in the Uniform Determination of Death Act; and 3) does not violate the “Dead Donor Rule.” Conclusions:The use of unmodified extracorporeal membrane oxygenation in the circulatory determination of death donor after death is declared should be abandoned because, by restoring brain circulation, it retroactively negates the previous death determination. Modifications of extracorporeal membrane oxygenation that avoid this problem by excluding brain circulation are contrived, invasive, and, if used, should require consent of surrogates. Heart donation in circulatory determination of death is acceptable if proper standards are followed to declare donor death after establishing the permanent cessation of circulation. Pending additional data on “auto-resuscitation,” we recommend that all circulatory determination of death programs should utilize the prevailing standard of 2 to 5 mins of demonstrated mechanical asystole before declaring death.

Management of the Potential Organ Donor in the ICU: Society of Critical Care Medicine/American College of Chest Physicians/Association of Organ Procurement Organizations Consensus Statement

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Preinjury warfarin worsens outcome in elderly patients who fall from standing

INTRODUCTION Fall from standing (FFS) has become one of the most common mechanisms of injury for admission to the trauma center in the elderly population. Many of these patients present anticoagulated with warfarin. This two-center study was designed to examine the effects of preinjury warfarin use on outcome in the elderly. METHODS A retrospective review of prospectively collected registry data at two Level I trauma centers was conducted from 2003 to 2006. The study population included patients age > or = 65 admitted to the trauma center after an FFS. These centers are relatively close geographically and have similar patient demographics. Data collected included: age, Injury Severity Score, Abbreviated Injury Score (AIS) for head, mortality, admission Glasgow Coma Score, and admission international normalized ratio (INR). Patients were divided into two groups based on the preinjury condition of warfarin use. Statistical differences were determined by unpaired t test for continuous variables and chi and odds ratios (ORs) for dichotomous variables. RESULTS Of the 27,812 patients admitted to these two trauma centers over this time period, 2,791 (10.0%) were of age > or = 65 and admitted after an FFS. INR was 2.8 +/- 1.1 in warfarin group (+warf). The number of patients with AIS head 4 and 5 was similar between groups (-warf 22.1%, +warf 25.9%). Overall, preinjury warfarin use had a negative effect on the in-hospital mortality rate, +warf 8.6% and -warf 5.7% (OR 1.54, 1.09-2.19, p = 0.015). There was no difference in mortality between groups in patients with an AIS head < 4. The negative impact of preinjury warfarin use on mortality was most pronounced in patients with an AIS head 4 and 5 who presented awake (Glasgow Coma Score 14 and 15), +warf 13.5% and -warf 6.4% (OR 2.30, 95% confidence interval 1.12-4.70, p = 0.019). CONCLUSION Preinjury warfarin use has an adverse effect on outcome (mortality) in elderly FFS patients. Importantly, this effect is most prominent in patients admitted awake with significant findings on computed tomography scan. This argues for rapid emergency department triage to computed tomography scan and rapid INR correction in this population.

Safety and efficacy of propofol with EDTA when used for sedation of surgical intensive care unit patients.

Objective: To compare propofol with disodium edetate (EDTA) and propofol without EDTA when used for the sedation of critically ill surgical intensive care unit (ICU) patients. Design: Prospective, randomised, multicentre trial. Patients: A total of 122 surgical ICU patients who required intubation and mechanical ventilation. Interventions: Patients were randomised to receive either propofol or propofol plus EDTA (propofol EDTA) by continuous infusion for sedation. Measurements and Results: The addition of EDTA to propofol had no effect on calcium or magnesium homeostasis, renal function, haemodynamic function, or efficacy when used for the sedation of surgical patients in the ICU. The most common adverse events were hypotension, atrial fibrillation, and hypocalcaemia. In this trial, a greater number of serious adverse events and adverse events leading to withdrawal occurred in the propofol group relative to the propofol EDTA group. There was a significantly lower crude mortality rate at 7 and 28 days for the propofol EDTA group compared with the propofol group. There were no statistically significant differences between groups with respect to depth of sedation. Conclusion: The propofol EDTA formulation had no effect on calcium or magnesium homeostasis, renal function, or sedation efficacy compared with propofol alone when used for sedation in critically ill surgical ICU patients. There was a significant decrease in mortality in the propofol EDTA group compared with the propofol group. Further investigations are needed to validate this survival benefit and elucidate a possible mechanism.

Circulatory Death Determination in Uncontrolled Organ Donors: A Panel Viewpoint

One barrier for implementing programs of uncontrolled organ donation after the circulatory determination of death is the lack of consensus on the precise moment of death. Our panel was convened to study this question after we performed a similar analysis on the moment of death in controlled organ donation after the circulatory determination of death. We concluded that death could be determined by showing the permanent or irreversible cessation of circulation and respiration. Circulatory irreversibility may be presumed when optimal cardiopulmonary resuscitation efforts have failed to restore circulation and at least a 7-minute period has elapsed thereafter during which autoresuscitation to restored circulation could occur. We advise against the use of postmortem organ support technologies that reestablish circulation of warm oxygenated blood because of their risk of retroactively invalidating the required conditions on which death was declared.

Trace Element Homeostasis During Continuous Sedation With Propofol Containing EDTA Versus Other Sedatives in Critically Ill Patients

Objective: To evaluate changes in serum and urinary zinc, cobalt, copper, iron, and calcium concentrations in critically ill patients receiving propofol containing disodium edetate (disodium ethylenediaminetetraacetic acid [EDTA]) versus sedative agents without EDTA. Design: This was a randomised, open-label, parallel-group study with randomisation stratified by baseline Acute Physiology and Chronic Health Evaluation (APACHE II) scores. Setting: Intensive care units (ICU) in 23 medical centres. Patients: Medical, surgical, or trauma ICU patients 17 years of age or older who required mechanical ventilator support and sedation. Interventions: A total of 106 patients received propofol containing 0.005 % EDTA (propofol EDTA), and 104 received other sedative agents without EDTA (non-EDTA). Only the first 108 patients were assessed for urinary trace metal excretion. Twenty-four–hour urine samples were collected on days 2, 3, and 7 and every 7 days thereafter for determination of zinc, cobalt, copper, iron, and calcium excretion; EDTA levels; urine osmolality; albumin levels; and glucose levels. The first 143 patients were assessed for serum concentration of zinc, cobalt, copper, iron, and calcium; creatinine; blood urea nitrogen; and albumin at baseline and once during each 24-hour urine collection. Measurements and Results: For the assessment of trace metals, patients receiving propofol EDTA demonstrated increased mean urinary excretion of zinc, copper, and iron compared with the normal range. All patients receiving sedatives demonstrated increased urinary excretion of zinc and copper above normal reference values. Compared with the non-EDTA sedative group, the propofol EDTA group demonstrated increased urinary excretion of zinc and iron. Mean serum concentrations of zinc and total calcium were decreased in both patient groups. Serum zinc concentrations increased from baseline to day 3 in the non-EDTA sedative group but not in the propofol EDTA group. Renal function, measured by blood urea nitrogen, serum creatinine, and creatinine clearance, did not deteriorate during ICU sedation with either regimen. Conclusion: This study showed that critical illness is associated with increased urinary losses of zinc, copper, and iron. Propofol EDTA– treated patients had greater urinary losses of zinc and iron and lower serum zinc concentrations compared with the non-EDTA sedative group. No adverse events indicative of trace metal deficiency were observed in either group. The clinical significance of trace metal losses during critical illness is unclear and requires further study.

A multidisciplinary approach to adverse drug events in pediatric trauma patients in an adult trauma center.

Background: Adult trauma centers are major providers of medical management for pediatric trauma patients in the United States. Medication administration in this patient population is complex and fraught with potential error. Methods: We designed a multidisciplinary team consisting of a pediatric hospitalist, pediatric care coordinator, pediatric nurse, pharmacist, and the trauma service to manage pediatric trauma patients from admission until discharge. The team mandated collective decision making for medication dosing and administration, weight documentation, and implemented a medication error reporting system. Our goal was to derive and implement a multidisciplinary practice and education-based model of pediatric trauma patient care to identify and decrease adverse medication events. Results: Two hundred fifty-nine pediatric trauma patients were studied from January 1, 2003 to December 31, 2004, 125 pre-team implementation (control group) and 134 post-team implementation (study group). There were no significant differences in age, sex, mechanism of injury, injury severity score, or hospital length of stay between groups. There were significant reductions in number of medication prescribing errors (25 vs 15 errors; P = 0.05) and number of medication administration errors (19 vs 9 errors; P = 0.05) in the study group. Weight documentation improved significantly in the study group (90% vs 81%; P = 0.048). Conclusions: Instituting a multidisciplinary approach to pediatric trauma patient care is practical and can significantly decrease adverse medication events.

Intravenous esomeprazole pharmacodynamics in critically ill patients

Abstract Objective: A widely held belief contends that food-induced proton pump activation is important for optimal proton pump inhibitor–induced inhibition of gastric acid secretion. This study was undertaken to assess intragastric acid control with intravenous (IV) esomeprazole in critically ill patients. Research design and methods: This open-label, single-arm, exploratory trial was conducted at five university or regional hospital intensive care units in the US. Adult patients admitted to an intensive care unit who required mechanical ventilation and had at least one additional risk factor for stress-induced ulcer received twice-daily IV esomeprazole 40 mg for 48 hours and could continue for another 24 hours if no prepyloric enteral feedings were planned. Clinical trial registration: Trial registration: ClinicalTrials.gov identifier: NCT00428701. Main outcome measures: The primary efficacy variable was the linear-interpolated percentage of time intragastric pH was ≥4 during 24–48 hours. Secondary efficacy variables included the interpolated percentage of time intragastric pH was ≥4 during 0–24, 0–48, and 48–72 hours, the percentage of gastric aspirates collected with pH ≥4 during 0–24, 24–48, 0–48, and 48–72 hours, and time to stable pH ≥4. Safety was assessed based on adverse events (AEs), physical examinations, vital signs, laboratory tests, and electrocardiograms. Results: Forty-five patients were enrolled (one was excluded because of previous partial gastrectomy). Interpolated mean percentage time pH ≥4 was 88.8%, 80.7%, and 83.5% for 24–48, 0–24, and 0–48 hours, respectively. For 0–72 hours, ≥78% of gastric aspirates had pH ≥4. Median time to stable pH was 1 hour (95% confidence interval: 0.67, 2.00). Treatment was well tolerated, with no evidence of gastrointestinal bleeding. A total of 75 AEs occurred in 34 patients, none considered treatment related. Conclusions: In this noncontrolled exploratory study, twice-daily IV esomeprazole 40 mg rapidly decreased intragastric acidity and effectively maintained pH ≥4 during 0–72 hours in fasting, critically ill, mechanically ventilated patients at high risk for stress ulcers.

Emergency repair of a radiation-induced aortoesophageal fistula with endograft: report of a case.

This report presents the case of the emergency repair of a radiation-induced aortoesophageal fistula (AEF) with an endograft. The patient presented with multiple episodes of upper gastrointestinal bleeding. The fistula was discovered and treated in the operating room. The placement of a temporary aortic endograft was successful. The patient unfortunately exsanguinated while awaiting definitive aortic and esophageal repair. The potential occurrence of AEF should be considered in any patient presenting with massive hematemesis without a clear source of the bleeding. Although the patient succumbed to the fistula, this case illustrates the cryptic nature of an AEF and the difficult issues that are inherent in its treatment.