J Steven Hata

Out-of-hospital Hypertonic Resuscitation After Traumatic Hypovolemic Shock A Randomized, Placebo Controlled Trial

Objective: To determine whether out-of-hospital administration of hypertonic fluids would improve survival after severe injury with hemorrhagic shock. Background: Hypertonic fluids have potential benefit in the resuscitation of severely injured patients because of rapid restoration of tissue perfusion, with a smaller volume, and modulation of the inflammatory response, to reduce subsequent organ injury. Methods: Multicenter, randomized, blinded clinical trial, May 2006 to August 2008, 114 emergency medical services agencies in North America within the Resuscitation Outcomes Consortium. Inclusion criteria: injured patients, age ≥ 15 years with hypovolemic shock (systolic blood pressure ⩽ 70 mm Hg or systolic blood pressure 71–90 mm Hg with heart rate ≥ 108 beats per minute). Initial resuscitation fluid, 250 mL of either 7.5% saline per 6% dextran 70 (hypertonic saline/dextran, HSD), 7.5% saline (hypertonic saline, HS), or 0.9% saline (normal saline, NS) administered by out-of-hospital providers. Primary outcome was 28-day survival. On the recommendation of the data and safety monitoring board, the study was stopped early (23% of proposed sample size) for futility and potential safety concern. Results: A total of 853 treated patients were enrolled, among whom 62% were with blunt trauma, 38% with penetrating. There was no difference in 28-day survival—HSD: 74.5% (0.1; 95% confidence interval [CI], −7.5 to 7.8); HS: 73.0% (−1.4; 95% CI, −8.7–6.0); and NS: 74.4%, P = 0.91. There was a higher mortality for the postrandomization subgroup of patients who did not receive blood transfusions in the first 24 hours, who received hypertonic fluids compared to NS [28-day mortality—HSD: 10% (5.2; 95% CI, 0.4–10.1); HS: 12.2% (7.4; 95% CI, 2.5–12.2); and NS: 4.8%, P < 0.01]. Conclusion: Among injured patients with hypovolemic shock, initial resuscitation fluid treatment with either HS or HSD compared with NS, did not result in superior 28-day survival. However, interpretation of these findings is limited by the early stopping of the trial. Clinical Trial Registration: Clinical Trials.gov, NCT00316017

Randomized, double-blind comparison of immediate-release omeprazole oral suspension versus intravenous cimetidine for the prevention of upper gastrointestinal bleeding in critically ill patients.

Objective:To demonstrate that a new immediate-release omeprazole oral suspension is effective in preventing upper gastrointestinal bleeding in critically ill patients. Design:A noninferiority analysis was used to compare rates of clinically significant upper gastrointestinal bleeding in a prospective, phase 3, double-blind trial with parallel omeprazole suspension and cimetidine treatment groups. Setting:A total of 47 intensive care units in the United States. Patients:A total of 359 critically ill patients who required mechanical ventilation for ≥48 hrs, had an Acute Physiology and Chronic Health Evaluation score of ≥11 at baseline, had an intact stomach with a nasogastric or orogastric tube in place, and had at least one additional risk factor for upper gastrointestinal bleeding. Interventions:Patients were randomized to treatment with omeprazole suspension (two 40-mg doses on day 1, via orogastric or nasogastric tube, and 40 mg each day thereafter) or intravenous cimetidine (300-mg bolus and 50 mg/hr thereafter) for up to 14 days. Gastric aspirates were sampled for bleeding and pH. Medication doses were doubled for failure of pH control (two successive aspirates with pH ≤ 4). Measurements and Main Results:Clinically significant upper gastrointestinal bleeding (bright red blood not clearing after 5–10 mins of lavage or persistent Gastroccult-positive “coffee-grounds” material for 8 hrs on days 1–2 or for 2–4 hrs on days 3–14 and not clearing with ≥100 mL of lavage) was the primary end point of the trial. The rate of clinically significant bleeding in the per-protocol population was 4.5% with omeprazole suspension and 6.8% with cimetidine, meeting the criteria for the noninferiority of omeprazole suspension. Median gastric pH was ≥6 on all trial days with omeprazole suspension treatment and on 50% of days with cimetidine treatment (p < .001, all trial days). In the omeprazole suspension group, median gastric pH was >4 on each trial day in 95% of patients. Conclusions:Immediate-release omeprazole suspension is effective in preventing upper gastrointestinal bleeding and more effective than intravenous cimetidine in maintaining gastric pH of >4 in critically ill patients.

Hypertonic Resuscitation: Design and Implementation of a Prehospital Intervention Trial

BACKGROUND Trauma is the leading cause of death among North Americans between the ages of 1 and 44 years. Resuscitation with hypertonic saline (7.5%) solutions can reduce mortality in hypotensive and brain-injured patients. STUDY DESIGN Two multicenter, randomized, clinical trials were designed to compare hypertonic saline resuscitation with or without dextran with conventional isotonic resuscitation in patients with hypovolemic shock or traumatic brain injury. During a 3-year period, 5,848 patients will be randomized, with a primary end point of 28-day survival in the hypovolemic shock cohort and 6-month neurologic outcomes in the traumatic brain injury cohort. RESULTS This is a report of the study design and implementation of 2 large-scale prehospital intervention trials from the Resuscitation Outcomes Consortium that qualify for exception from informed consent required for emergency research outlined in FDA regulation 21CFR50.24 and the Canadian Tri-Council Agreement for research in emergency health situations (Article 2.8). CONCLUSIONS We have successfully designed and implemented two prehospital intervention trials. The proc-ess has helped define the numerous challenges that must be overcome to pursue exception from informed consent resuscitation research in the prehospital setting. The results of these studies will hopefully advance and improve the early care of the severely injured patient.

Impact of transesophageal echocardiography on the anticoagulation management of patients admitted with focal cerebral ischemia

Transesophageal echocardiography (TEE) improves the diagnostic accuracy of transthoracic echocardiography in the identification of potential cardiac sources of embolus. However, there are few studies of the impact of TEE on the medical management of patients with focal cerebral ischemia. The records of 52 consecutive, hospitalized patients undergoing both TEE and transthoracic echocardiography for suspected cardiac source of embolus were reviewed to determine the influence of TEE on the decision to anticoagulate patients. Of 52 patients, 39 had focal cerebral ischemia (transient ischemic attack, n = 9; acute cerebral infarction, n = 30). In 4 of these 39 patients (10%), the TEE results changed the management of anticoagulation. In 19 of 39 patients (49%), the TEE results helped confirm anticoagulation decisions, and in 16 (41%), the results had no effect on anticoagulation decisions, because of overriding clinical information. Ten of the latter 16 patients had TEE evidence for a possible source of an embolus, but were not anticoagulated; 5 of these were poor candidates for long-term anticoagulation, and the others had right-to-left shunting across a patent foramen ovale or an interatrial septal aneurysm. Clinical variables (atrial fibrillation, TEE findings and pre-TEE anticoagulation status) were considered as possible predictors of post-TEE anticoagulation status using logistic regression analysis; the strongest predictor of post-TEE anticoagulation status was pre-TEE anticoagulation status (p < 0.0005). Despite the selection of patients presumed to receive maximal benefit from TEE, this study suggests that TEE findings are not predictive of subsequent anticoagulation management. However, TEE is at least confirmatory of anticoagulation decisions in most cases.

Procedures and Monitoring for the Critically Ill

Procedures and Monitoring for the Critically Ill is a multi-authored manual, detailing 29 procedures and monitoring techniques used in intensive care. This is an expedient, introductory critical care reference, particularly for physicians in training. The topics are pragmatic, describing common procedural topics for intensive care. Typically, each area has an effective description of the methods and illustrations of the techniques. A bibliography of key references accompanies each chapter. Succinct descriptions of step by step methods as well as the required supplies are included for 1) hemodynamic monitoring (e.g., central venous pressure, pulmonary artery catheterization, arterial catheterization); 2) neurologic monitoring (e.g., intra-cranial pressure monitoring, jugular bulb oximetry); 3) trauma related areas (e.g., spinal immobilization, intra-abdominal pressure monitoring, abdominal paracentesis; 4) emergency airway support (e.g., endotracheal intubation, cricothryrotomy, bronchoscopy, and tracheostomy); as well as 5) other areas including transesophageal Doppler monitoring, epidural analgesia, renal support, and inferior vena cava filter placement. For greater detail in ICU monitoring procedures, interested readers are recommended to more encyclopedic texts, such as Principles and Practices of Intensive Care Medicine, edited by M.Tobin. In summary, this text is a useful reference during the preliminary years of training for critical care or rapid review of methodologies of ICU procedures and monitoring techniques.