Steven Deem

Pilot Randomized Clinical Trial of Prehospital Induction of Mild Hypothermia in Out-of-Hospital Cardiac Arrest Patients With a Rapid Infusion of 4°C Normal Saline

Background— Although delayed hospital cooling has been demonstrated to improve outcome after cardiac arrest, in-field cooling started immediately after the return of spontaneous circulation may be more beneficial. The aims of the present pilot study were to assess the feasibility, safety, and effectiveness of in-field cooling. Methods and Results— We determined the effect on esophageal temperature, before hospital arrival, of infusing up to 2 L of 4°C normal saline as soon as possible after resuscitation from out-of-hospital cardiac arrest. A total of 125 such patients were randomized to receive standard care with or without intravenous cooling. Of the 63 patients randomized to cooling, 49 (78%) received an infusion of 500 to 2000 mL of 4°C normal saline before hospital arrival. These 63 patients experienced a mean temperature decrease of 1.24±1°C with a hospital arrival temperature of 34.7°C, whereas the 62 patients not randomized to cooling experienced a mean temperature increase of 0.10±0.94°C (P<0.0001) with a hospital arrival temperature of 35.7°C. In-field cooling was not associated with adverse consequences in terms of blood pressure, heart rate, arterial oxygenation, evidence for pulmonary edema on initial chest x-ray, or rearrest. Secondary end points of awakening and discharged alive from hospital trended toward improvement in ventricular fibrillation patients randomized to in-field cooling. Conclusions— These pilot data suggest that infusion of up to 2 L of 4°C normal saline in the field is feasible, safe, and effective in lowering temperature. We propose that the effect of this cooling method on neurological outcome after cardiac arrest be studied in larger numbers of patients, especially those whose initial rhythm is ventricular fibrillation.

Effect of prehospital induction of mild hypothermia on survival and neurological status among adults with cardiac arrest: a randomized clinical trial.

IMPORTANCE Hospital cooling improves outcome after cardiac arrest, but prehospital cooling immediately after return of spontaneous circulation may result in better outcomes. OBJECTIVE To determine whether prehospital cooling improves outcomes after resuscitation from cardiac arrest in patients with ventricular fibrillation (VF) and without VF. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial that assigned adults with prehospital cardiac arrest to standard care with or without prehospital cooling, accomplished by infusing up to 2 L of 4°C normal saline as soon as possible following return of spontaneous circulation. Adults in King County, Washington, with prehospital cardiac arrest and resuscitated by paramedics were eligible and 1359 patients (583 with VF and 776 without VF) were randomized between December 15, 2007, and December 7, 2012. Patient follow-up was completed by May 1, 2013. Nearly all of the patients resuscitated from VF and admitted to the hospital received hospital cooling regardless of their randomization. MAIN OUTCOMES AND MEASURES The primary outcomes were survival to hospital discharge and neurological status at discharge. RESULTS The intervention decreased mean core temperature by 1.20°C (95% CI, -1.33°C to -1.07°C) in patients with VF and by 1.30°C (95% CI, -1.40°C to -1.20°C) in patients without VF by hospital arrival and reduced the time to achieve a temperature of less than 34°C by about 1 hour compared with the control group. However, survival to hospital discharge was similar among the intervention and control groups among patients with VF (62.7% [95% CI, 57.0%-68.0%] vs 64.3% [95% CI, 58.6%-69.5%], respectively; P = .69) and among patients without VF (19.2% [95% CI, 15.6%-23.4%] vs 16.3% [95% CI, 12.9%-20.4%], respectively; P = .30). The intervention was also not associated with improved neurological status of full recovery or mild impairment at discharge for either patients with VF (57.5% [95% CI, 51.8%-63.1%] of cases had full recovery or mild impairment vs 61.9% [95% CI, 56.2%-67.2%] of controls; P = .69) or those without VF (14.4% [95% CI, 11.3%-18.2%] of cases vs 13.4% [95% CI,10.4%-17.2%] of controls; P = .30). Overall, the intervention group experienced rearrest in the field more than the control group (26% [95% CI, 22%-29%] vs 21% [95% CI, 18%-24%], respectively; P = .008), as well as increased diuretic use and pulmonary edema on first chest x-ray, which resolved within 24 hours after admission. CONCLUSION AND RELEVANCE Although use of prehospital cooling reduced core temperature by hospital arrival and reduced the time to reach a temperature of 34°C, it did not improve survival or neurological status among patients resuscitated from prehospital VF or those without VF. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00391469.

Pilot Study of Rapid Infusion of 2 L of 4°C Normal Saline for Induction of Mild Hypothermia in Hospitalized, Comatose Survivors of Out-of-Hospital Cardiac Arrest

Background—Recent clinical studies have demonstrated that mild hypothermia (32°C to 34°C) induced by surface cooling improves neurological outcome after resuscitation from out-of-hospital cardiac arrest. Results from animal models suggest that the effectiveness of mild hypothermia could be improved if initiated as soon as possible after return of spontaneous circulation. Infusion of cold, intravenous fluid has been proposed as a safe, effective, and inexpensive technique to induce mild hypothermia after cardiac arrest. Methods and Results—In 17 hospitalized survivors of out-of-hospital cardiac arrest, we determined the effect on temperature and hemodynamics of infusing 2 L of 4°C cold, normal saline during 20 to 30 minutes into a peripheral vein with a high-pressure bag. Data on vital signs, electrolytes, arterial blood gases, and coagulation were collected before and after fluid infusion. Cardiac function was assessed by transthoracic echocardiography before fluid administration and 1 hour after infusion. Passive (fans, leaving patient uncovered) or active (cooling blankets, neuromuscular blockade) cooling measures were used to maintain mild hypothermia for 24 hours. Infusion of 2 L of 4°C cold, normal saline resulted in a mean temperature drop of 1.4°C 30 minutes after the initiation of infusion. Rapid infusion of fluid was not associated with clinically important changes in vital signs, electrolytes, arterial blood gases, or coagulation parameters. The initial mean ejection fraction was 34%, and fluid infusion did not affect ejection fraction or increase central venous pressure, pulmonary pressures, or left atrial filling pressures as assessed by echocardiography. Passive measures were ineffective in maintaining hypothermia compared with active measures. Conclusions—Infusion of 2 L of 4°C cold, normal saline is safe and effective in rapidly lowering body temperature in survivors of out-of-hospital cardiac arrest.

Randomized trial of light versus deep sedation on mental health after critical illness

Objectives:To investigate if light sedation favorably affects subsequent patient mental health compared with deep sedation. Symptoms of posttraumatic stress disorder are common in patients after they have undergone prolonged mechanical ventilation and are associated with sedation depth. Design:Randomized, open-label, controlled trial. Setting:Single tertiary care center. Patients:Adult patients requiring mechanical ventilation. Interventions:Patients were randomized to receive either light (patient awake and cooperative) or deep sedation (patient asleep, awakening upon physical stimulation). Measurements and Main Results:Self-reported measures of posttraumatic stress disorder, anxiety, and depression were collected at intensive care unit discharge and 4 wks later. The primary outcomes were symptoms of posttraumatic stress disorder, anxiety, and depression 4 wks after intensive care unit discharge. A total of 137 patients were assigned to either the light (n = 69) or the deep sedation (n = 68) group. Seven patients withdrew consent and one patient was randomized in error, leaving 129 patients (n = 65 in light sedation and n = 64 in deep sedation) available for analysis. At the 4-wk follow-up, patients in the deep sedation group tended to have more posttraumatic stress disorder symptoms (p = .07); the deep sedation group had more trouble remembering the event (37% vs. 14%; p = .02) and more disturbing memories of the intensive care unit (18% vs. 4%; p = .05). Patients in the light sedation group had an average one day less being ventilated and 1.5 fewer days in the intensive care unit. There were no differences between the two groups in the occurrence of anxiety and depression, and also no difference in mortality or in the incidence of adverse events. Conclusions:These data suggest that a strategy of light sedation affords benefits with regard to reduction of intensive care unit stay and duration of ventilation without negatively affecting subsequent patient mental health or patient safety.

Intensive insulin therapy and mortality in critically ill patients.

IntroductionIntensive insulin therapy (IIT) with tight glycemic control may reduce mortality and morbidity in critically ill patients and has been widely adopted in practice throughout the world. However, there is only one randomized controlled trial showing unequivocal benefit to this approach and that study population was dominated by post-cardiac surgery patients. We aimed to determine the association between IIT and mortality in a mixed population of critically ill patients.MethodsWe conducted a cohort study comparing three consecutive time periods before and after IIT protocol implementation in a Level 1 trauma center: period I (no protocol); period II, target glucose 80 to 130 mg/dL; and period III, target glucose 80 to 110 mg/dL. Subjects were 10,456 patients admitted to intensive care units (ICUs) between 1 March 2001 and 28 February 2005. The main study endpoints were ICU and hospital mortality, Sequential Organ Failure Assessment score, and occurrence of hypoglycemia. Multivariable regression analysis was used to evaluate mortality and organ dysfunction during periods II and III relative to period I.ResultsInsulin administration increased over time (9% period I, 25% period II, and 42% period III). Nonetheless, patients in period III had a tendency toward higher adjusted hospital mortality (odds ratio [OR] 1.15, 95% confidence interval [CI] 0.98, 1.35) than patients in period I. Excess hospital mortality in period III was present primarily in patients with an ICU length of stay of 3 days or less (OR 1.47, 95% CI 1.11, 1.93 There was an approximately fourfold increase in the incidence of hypoglycemia from periods I to III.ConclusionA policy of IIT in a group of ICUs from a single institution was not associated with a decrease in hospital mortality. These results, combined with the findings from several recent randomized trials, suggest that further study is needed prior to widespread implementation of IIT in critically ill patients.

Active surface cooling protocol to induce mild therapeutic hypothermia after out-of-hospital cardiac arrest: a retrospective before-and-after comparison in a single hospital.

Objective: To evaluate whether implementation of a therapeutic hypothermia protocol on arrival in a community hospital improved survival and neurologic outcomes in patients initially found to have ventricular fibrillation, pulseless electrical activity, or asystole, and then successfully resuscitated from out-of-hospital cardiac arrest. Design: A retrospective study of patients who presented after implementation of a therapeutic hypothermia protocol compared with those who presented before the protocol was implemented. Setting: Harborview Medical Center, Seattle, WA. Patients: A total of 491 consecutive adults with out-of-hospital, nontraumatic cardiac arrest who presented between January 1, 2000 and December 31, 2004. Interventions: An active cooling therapeutic hypothermia protocol, using ice packs, cooling blankets, or cooling pads to achieve a temperature of 32°C to 34°C was initiated on November 18, 2002 for unconscious patients resuscitated from cardiac arrest. Measurements and Main Results: Demographics and outcomes were obtained from medical records and an emergency medical database. The primary outcomes were survival and favorable neurologic outcome at discharge associated with the therapeutic hypothermia protocol. An adjusted analysis was performed, using a multivariate regression. During the therapeutic hypothermia period, 204 patients were brought to the emergency department; of these 204 patients, 132 (65%) ultimately achieved temperatures of <34°C. Of the 72 patients who did not achieve goal temperatures: 40 (20%) died in the emergency department or shortly after being admitted to the hospital, 15 (7%) regained consciousness, four (2%) had contraindications, 13 (6%) had temperature increase or did not have documented use of the therapeutic hypothermia protocol. In the prior period, none of the 287 patients received active cooling. Patients admitted in the therapeutic hypothermia period had a mean esophageal temperature of 34.1°C during the first 12 hrs compared with 35.2°C in the pretherapeutic hypothermia period (p < .01). Survival to hospital discharge improved in the therapeutic hypothermia period in patients with an initial rhythm of ventricular fibrillation (odds ratio, 1.88, 95% confidence interval, 1.03–3.45), however not in patients with nonventricular fibrillation (odds ratio, 1.17, 95% confidence interval, 0.66–2.05). In adjusted analysis, ventricular fibrillation patients during the therapeutic hypothermia period trended toward improved survival (odds ratio, 1.71, 95% confidence interval, 0.85–3.46) and had favorable neurologic outcome (odds ratio, 2.62, 95% confidence interval, 1.1–6.27) compared with the earlier period. This benefit was not observed in patients whose initial rhythm was pulseless electrical activity or asystole. Conclusions: The therapeutic hypothermia period was associated with a significant improvement in neurologic outcomes in patients whose initial rhythm was ventricular fibrillation, but not in patients with other rhythms.

Acute lung injury in patients with subarachnoid hemorrhage

Objective:Pulmonary complications account for significant morbidity and mortality following aneurysmal subarachnoid hemorrhage; however, the effect of acute lung injury is largely unknown. The goal of this study was to determine the incidence of acute lung injury in a large cohort of patients with subarachnoid hemorrhage as well as determine the risk factors for acute lung injury and its effect on mortality and length of stay. Ventilator management was analyzed to determine the proportion of patients with subarachnoid hemorrhage and acute lung injury who a received a low-tidal volume ventilation strategy. Design:Retrospective cohort study. Setting:University-affiliated county hospital in Seattle, WA. Patients:Six-hundred and twenty patients with aneurysmal subarachnoid hemorrhage documented on computed tomography or angiography. Interventions:None. Measurements and Main Results:One-hundred and seventy patients met criteria for acute lung injury (incidence, 27%; 95% confidence interval, 24–31%). On multivariate analysis, severity of illness, clinical grade of hemorrhage, packed red blood cell transfusions, and severe sepsis in the intensive care unit were independently associated with development of acute lung injury. After adjustment for important confounders, development of acute lung injury was associated with a statistically significant increase in hospital mortality (odds ratio, 1.63; 95% confidence interval, 1.03–2.57). Acute lung injury was also independently associated with an increased intensive care unit length of stay (15%, 95% confidence interval, 5–27%). Thirty percent of patients with acute lung injury received low tidal volume ventilation. Patients receiving low tidal volume ventilation had worse oxygenation and higher positive end-expiratory pressure requirements compared with those who did not, but there were no significant differences in arterial pH or Pco2. Conclusions:Acute lung injury is common in patients with subarachnoid hemorrhage and is independently associated with a worse clinical outcome. Research is needed to determine the causes of acute lung injury in this population and whether these patients are candidates for evidence-based ventilator strategies to reduce mortality.

Management guided by brain tissue oxygen monitoring and outcome following severe traumatic brain injury.

OBJECT The authors sought to describe changes in clinical management associated with brain tissue oxygen (PbO(2)) monitoring and how these changes affected outcomes and resource utilization. METHODS The cohort study comprised 629 patients admitted to a Level I trauma center with a diagnosis of severe traumatic brain injury over a period of 3 years. Hospital mortality rate, neurological outcome, and resource utilization of 123 patients who underwent both PbO(2) and intracranial pressure (ICP) monitoring were compared with the same measures in 506 patients who underwent ICP monitoring only. The main outcomes were hospital mortality rate, functional independence at hospital discharge, duration of mechanical ventilation, hospital length of stay, and hospital cost. Multivariable regression with robust variance was used to estimate the adjusted differences in the main outcome measures between patient groups. The models were adjusted for patient age, severity of injury, and pathological features seen on head CT scan at admission. RESULTS On average, patients who underwent ICP/PbO(2) monitoring were younger and had more severe injuries than patients who received ICP monitoring alone. Relatively more patients treated with PbO(2) monitoring received osmotic therapy, vasopressors, and prolonged sedation. After adjustment for baseline characteristics, the hospital mortality rate was, if anything, slightly higher in patients undergoing PbO(2)-guided management than in patients monitored with ICP only (adjusted mortality difference 4.4%, 95% CI -3.9 to 13%). Patients who underwent PbO(2)-guided management also had lower adjusted functional independence scores at hospital discharge (adjusted score difference -0.75, 95% CI -1.41 to -0.09). There was a 27% relative increase (95% CI 6-53%) in the median hospital length of stay when the PbO(2) group was compared with the ICP-only group. CONCLUSIONS The mortality rate in patients with traumatic brain injury whose clinical management was guided by PbO(2) monitoring was not reduced in comparison with that in patients who received ICP monitoring alone. Brain tissue oxygen monitoring was associated with worse neurological outcome and increased hospital resource utilization.

Characterization of cardiac dysfunction in sepsis: an ongoing challenge.

ABSTRACT Sepsis-induced cardiomyopathy (SIC), which is a common morbid condition, occurs in patients with severe sepsis and septic shock. The clinical characterization of SIC has been largely concept-driven. Heart function has traditionally been evaluated according to two basic conceptual models: a hydraulic pump system, whereby the output from the heart is entirely dependent on its input, or a hemodynamic pump, whereby the cardiac output is a function of preload, global ventricular performance, and afterload. Minimal attention has been given to the intrinsic contractile function of the heart or to the interaction between the peripheral circulation and the intrinsic myocardial function in sepsis. Currently, SIC is assumed to be the result of the interaction of microorganisms that activate the physiopathological pathways and cellular signaling mechanisms that lead to intrinsic myocardial dysfunction. However, the animal models used to study SIC exhibit multiple limitations. This review addresses the conceptual background, historical perspectives, physiologic mechanisms, current evidence, and limitations of SIC characterization. It also highlights potential future directions for the hemodynamic assessment of the intrinsic contractile function of the heart to overcome current methodological limitations. Finally, the present review recommends the exploration of additional potential mechanisms underlying SIC.

Which H is the most important in triple-H therapy for cerebral vasospasm?

Purpose of reviewTo summarize the recent literature of the hemodynamic management of subarachnoid hemorrhage and cerebral vasospasm, also designated as ‘triple-H’ therapy, and discuss each component of this management approach individually. Recent findingsFollowing the publication of a review on circulatory volume expansion in the Cochrane Registry database in 2004 and a meta-analysis in 2003, there are no new randomized trials of triple-H therapy to prevent or treat cerebral vasospasm. However, physiological studies have been reported that contribute to the understanding of some of the components of triple-H therapy. SummaryThere remains a paucity of information regarding the efficacy and safety of triple-H therapy. The complexity in exploring this topic derives not only from the interdependence of the different components of triple-H therapy but also by the limitation in the assessment of hemodynamic variables. However, there is some emerging physiologic data suggesting that normovolemic hypertension may be the component most likely to increase cerebral blood flow after subarachnoid hemorrhage. In contrast, hypervolemic hemodilution is associated with increased complications and might also lower the hemoglobin to excessively low levels.