NEJM 2009;361:2529-2537

Early repolarization, which is characterized by an elevation of the QRS–ST junction (J point) in leads other than V1 through V3 on 12-lead electrocardiography, has been associated with vulnerability to ventricular fibrillation, but little is known about the prognostic significance of this pattern in the general population.

Methods
We assessed the prevalence and prognostic significance of early repolarization on 12-lead electrocardiography in a community-based general population of 10,864 middle-aged subjects (mean [±SD] age, 44±8 years). The primary end point was death from cardiac causes, and secondary end points were death from any cause and death from arrhythmia during a mean follow-up of 30±11 years. Early repolarization was stratified according to the degree of J-point elevation (0.1 mV or >0.2 mV) in either inferior or lateral leads.

Results
The early-repolarization pattern of 0.1 mV or more was present in 630 subjects (5.8%): 384 (3.5%) in inferior leads and 262 (2.4%) in lateral leads, with elevations in both leads in 16 subjects (0.1%). J-point elevation of at least 0.1 mV in inferior leads was associated with an increased risk of death from cardiac causes (adjusted relative risk, 1.28; 95% confidence interval [CI], 1.04 to 1.59; P=0.03); 36 subjects (0.3%) with J-point elevation of more than 0.2 mV in inferior leads had a markedly elevated risk of death from cardiac causes (adjusted relative risk, 2.98; 95% CI, 1.85 to 4.92; P<0.001) and from arrhythmia (adjusted relative risk, 2.92; 95% CI, 1.45 to 5.89; P=0.01). Other electrocardiographic risk markers, such as a prolonged QT interval corrected for heart rate (P=0.03) and left ventricular hypertrophy (P=0.004), were weaker predictors of the primary end point.

Conclusions
An early-repolarization pattern in the inferior leads of a standard electrocardiogram is associated with an increased risk of death from cardiac causes in middle-aged subjects.

Crit Care Med – published ahead of print

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^oC to 34^oC 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^oC. 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^oC during the first 12 hrs compared with 35.2^oC in the pretherapeutic hypothermia period (p < 0.01). 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.

Cochr Database of Systematic Reviews, 2009;4

Good neurologic outcome after cardiac arrest is hard to achieve. Interventions during the resuscitation phase and treatment within the first hours after the event are critical. Experimental evidence suggests that therapeutic hypothermia is beneficial, and a number of clinical studies on this subject have been published.

Crit Care Med 2009;37:403-409

To evaluate the effects of therapeutic hypothermia (HT) of 33°C after cardiac arrest (CA) on cardiac arrhythmias, heart rate variability (HRV), and their prognostic value.

Design
Prospective, comparative substudy of a randomized controlled trial of mild HT after out-of-hospital CA, the European Hypothermia After Cardiac Arrest study.

Setting
Intensive care unit of a tertiary referral hospital (Helsinki University Hospital).

Patients
Seventy consecutive adult patients resuscitated from out-of-hospital ventricular fibrillation were randomly assigned either to therapeutic HT of 33°C or normothermia.

Interventions
Patients randomized to HT were cooled with an external cooling device for 24 hours and then allowed to rewarm slowly during 12 hours. In the normothermia group, the core temperature was kept <38°C by antipyretics and physical means. All patients received standard intensive care for at least 2 days.

Measurements and main results
Twenty-four hour ambulatory electrocardiography recordings were performed at 0-24 hours, at 24-48 hours, and at 14 days. The clinical outcome was assessed at 6 months after CA. The occurrence of premature ventricular beats was increased in the HT-treated group during the first two recordings, with no difference in the number of ventricular tachycardia or ventricular fibrillation episodes. All HRV values were significantly higher during the HT (p < 0.01), but no differences were observed 2 weeks later. In multivariate analysis, only shorter delay to restoration of spontaneous circulation (p = 0.009) and the sd of individual normal-to-normal intervals >100 msec of the 24-48-hour recording in the HT group (p = 0.018) predicted good outcome.

Conclusions
The use of therapeutic HT of 33°C for 24 hours after CA was not associated with an increase in clinically significant arrhythmias. Preserved 24 to 48-hour HRV may be a predictor of favorable outcome in patients with CA treated with HT.

NEJM 2008;359:21-30

During the administration of advanced cardiac life support for resuscitation from cardiac arrest, a combination of vasopressin and epinephrine may be more effective than epinephrine or vasopressin alone, but evidence is insufficient to make clinical recommendations.

Methods
In a multicenter study, we randomly assigned adults with out-of-hospital cardiac arrest to receive successive injections of either 1 mg of epinephrine and 40 IU of vasopressin or 1 mg of epinephrine and saline placebo, followed by administration of the same combination of study drugs if spontaneous circulation was not restored and subsequently by additional epinephrine if needed. The primary end point was survival to hospital admission; the secondary end points were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival.

Results
A total of 1442 patients were assigned to receive a combination of epinephrine and vasopressin, and 1452 to receive epinephrine alone. The treatment groups had similar baseline characteristics except that there were more men in the group receiving combination therapy than in the group receiving epinephrine alone (P=0.03). There were no significant differences between the combination-therapy and the epinephrine-only groups in survival to hospital admission (20.7% vs. 21.3%; relative risk of death, 1.01; 95% confidence interval [CI], 0.97 to 1.05), return of spontaneous circulation (28.6% vs. 29.5%; relative risk, 1.01; 95% CI, 0.97 to 1.06), survival to hospital discharge (1.7% vs. 2.3%; relative risk, 1.01; 95% CI, 1.00 to 1.02), 1-year survival (1.3% vs. 2.1%; relative risk, 1.01; 95% CI, 1.00 to 1.02), or good neurologic recovery at hospital discharge (37.5% vs. 51.5%; relative risk, 1.29; 95% CI, 0.81 to 2.06).

Conclusions
As compared with epinephrine alone, the combination of vasopressin and epinephrine during advanced cardiac life support for out-of-hospital cardiac arrest does not improve outcome.

N Engl J Med 2008;358:2016-2023

Early repolarization is a common electrocardiographic finding that is generally considered to be benign. Its potential to cause cardiac arrhythmias has been hypothesized from experimental studies, but it is not known whether there is a clinical association with sudden cardiac arrest.

Method
We reviewed data from 206 case subjects at 22 centers who were resuscitated after cardiac arrest due to idiopathic ventricular fibrillation and assessed the prevalence of electrocardiographic early repolarization. The latter was defined as an elevation of the QRS–ST junction of at least 0.1 mV from baseline in the inferior or lateral lead, manifested as QRS slurring or notching. The control group comprised 412 subjects without heart disease who were matched for age, sex, race, and level of physical activity. Follow-up data that included the results of monitoring with an implantable defibrillator were obtained for all case subjects.

Result
Early repolarization was more frequent in case subjects with idiopathic ventricular fibrillation than in control subjects (31% vs. 5%, P<0.001). Among case subjects, those with early repolarization were more likely to be male and to have a history of syncope or sudden cardiac arrest during sleep than those without early repolarization. In eight subjects, the origin of ectopy that initiated ventricular arrhythmias was mapped to sites concordant with the localization of repolarization abnormalities. During a mean (±SD) follow-up of 61±50 months, defibrillator monitoring showed a higher incidence of recurrent ventricular fibrillation in case subjects with a repolarization abnormality than in those without such an abnormality (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008).

Conclusions
Among patients with a history of idiopathic ventricular fibrillation, there is an increased prevalence of early repolarization.

Critical Care Medicine 2006;34:1865-1873

We sought to evaluate current physician use of therapeutic hypothermia after cardiac arrest, to ascertain reasons for nonadoption of this treatment, and to determine current cooling techniques employed.

Design
Web-based survey.

Setting
International physician cohort in the United States, UK, and Finland.

Subjects
Physicians (MD or DO) caring for resuscitated cardiac arrest patients.

Interventions
An anonymous Web-based survey was distributed to physicians identified through United States-based critical care, cardiology, and emergency medicine directories and critical care networks in the UK and Finland. Recipients were queried regarding use of postresuscitation therapeutic hypothermia.

Measurements and Main Results
Of the final 13,272 surveys actually distributed to physicians, 2,248 (17%) were completed. Most respondents were attending physicians (82%) at teaching hospitals (76%) who practiced critical care (35%), cardiology (20%), or emergency medicine (22%). Of all replies, 74% of United States respondents and 64% of non-United States respondents had never used therapeutic hypothermia. United States emergency medicine physician adoption of cooling was significantly less than that of United States intensivists (16% vs. 34%, p < .05). The most often cited reasons for nonuse by respondents were "not enough data," "not part of Advanced Cardiac Life Support guidelines," and "too technically difficult to use." Factors associated with increased use included non-United States residence, critical care specialty, and larger hospital size.

Conclusions
Physician utilization of cooling after cardiac arrest remains low. For improved adoption of therapeutic hypothermia, our data suggest that development of better cooling methodology and recent incorporation into resuscitation guidelines may improve use.

Critical Care 2006, 10:R51 http://ccforum.com/content/10/2/R51

Introduction
Abdominal compartment syndrome (ACS) is increasingly recognized in critically ill patients, and the deleterious effects of increased intraabdominal pressure (IAP) are well documented. Surgical decompression through a midline laparotomy or decompressive laparotomy remains the sole definite therapy for ACS, but the effect of decompressive laparotomy has not been studied in large patient series.

Methods
We reviewed English literature from 1972 to 2004 for studies reporting the effects of decompressive laparotomy in patients with ACS. The effect of decompressive laparotomy on IAP, patient outcome and physiology were analysed.

Results
Eighteen studies including 250 patients who underwent decompressive laparotomy could be included in the analysis. IAP was significantly lower after decompression (15.5 mmHg versus 34.6 mmHg before, p < 0.001), but intraabdominal hypertension persisted in the majority of the patients. Mortality in the whole group was 49.2% (123/250). The effect of decompressive laparotomy on organ function was not uniform, and in some studies no effect on organ function was found. Increased PaO₂/FIO₂ ratio (PaO₂ = partial pressure of oxygen in arterial blood, FiO₂ = fraction of inspired oxygen) and urinary output were the most pronounced effects of decompressive laparotomy.

Conclusion
The effects of decompressive laparotomy have been poorly investigated, and only a small number of studies report its effect on parameters of organ function. Although IAP is consistently lower after decompression, mortality remains considerable. Recuperation of organ dysfunction after decompressive laparotomy for ACS is variable.

N Engl J Med 2002;346:557-63.

Background
Cardiac arrest outside the hospital is common and has a poor outcome. Studies in laboratory animals suggest that hypothermia induced shortly after the restoration of spontaneous circulation may improve neurologic outcome, but there have been no conclusive studies in humans. In a randomized, controlled trial, we compared the effects of moderate hypothermia and normothermia in patients who remained unconscious after resuscitation from out– of-hospital cardiac arrest.

Methods
The study subjects were 77 patients who were randomly assigned to treatment with hypothermia (with the core body temperature reduced to 33 deg C within 2 hours after the return of spontaneous circulation and maintained at that temperature for 12 hours) or normothermia. The primary outcome measure was survival to hospital discharge with sufficiently good neurologic function to be discharged to home or to a rehabilitation facility.

Results
The demographic characteristics of the patients were similar in the hypothermia and normothermia groups. Twenty-one of the 43 patients treated with hypothermia (49 percent) survived and had a good outcome – that is, they were discharged home or to a rehabilitation facility – as compared with 9 of the 34 treated with normothermia (26 percent, P=0.046). After adjustment for base-line differences in age and time from collapse to the return of spontaneous circulation, the odds ratio for a good outcome with hypothermia as compared with normothermia was 5.25 (95 percent confidence interval, 1.47 to 18.76; P=0.011). Hypothermia was associated with a lower cardiac index, higher systemic vascular resistance, and hyperglycemia. There was no difference in the frequency of adverse events.

Conclusions
Our preliminary observations suggest that treatment with moderate hypothermia appears to improve outcomes in patients with coma after resuscitation from out-of-hospital cardiac arrest.

N Engl J Med 2002;346:549-56

Background
Cardiac arrest with widespread cerebral ischemia frequently leads to severe neurologic impairment. We studied whether mild systemic hypothermia increases the rate of neurologic recovery after resuscitation from cardiac arrest due to ventricular fibrillation.

Methods
In this multicenter trial with blinded assessment of the outcome, patients who had been resuscitated after cardiac arrest due to ventricular fibrillation were randomly assigned to undergo therapeutic hypothermia (target temperature, 32 deg C to 34 deg C, measured in the bladder) over a period of 24 hours or to receive standard treatment with normothermia. The primary end point was a favorable neurologic outcome within six months after cardiac arrest; secondary end points were mortality within six months and the rate of complications within seven days.

Results
Seventy-five of the 136 patients in the hypothermia group for whom data were available (55 percent) had a favorable neurologic outcome (cerebral– performance category, 1 [good recovery] or 2 [moderate disability]), as compared with 54 of 137 (39 percent) in the normothermia group (risk ratio, 1.40; 95 percent confidence interval, 1.08 to 1.81). Mortality at six months was 41 percent in the hypothermia group (56 of 137 patients died), as compared with 55 percent in the normothermia group (76 of 138 patients; risk ratio, 0.74; 95 percent confidence interval, 0.58 to 0.95). The complication rate did not differ significantly between the two groups.

Conclusions
In patients who have been successfully resuscitated after cardiac arrest due to ventricular fibrillation, therapeutic mild hypothermia increased the rate of a favorable neurologic outcome and reduced mortality.

N Engl J Med 2002;346:546

For decades, cooling the body below the normal physiologic temperature has been used as a therapeutic tool. Hypothermia is used most often during cardiac surgery with cardiopulmonary bypass, as a means of protecting the brain from ischemic injury. Hypothermia is also used during some neurosurgical procedures and is being investigated as a treatment for ischemic stroke and traumatic brain injury. In this issue of the Journal, two groups of investigators report on the use of therapeutic hypothermia to prevent neurologic injury in comatose survivors of cardiac arrest.

More than 350,000 Americans die as a result of sudden cardiac arrest every year (approximately 1,000 people every day). About 10-30% of long-term survivors have permanent brain damage as a result of global brain ischemia. Recently, hypothermia has been shown to make a difference. In 2002, two randomized, controlled, clinical trials demonstrated significantly improved outcomes in patients treated with hypothermia (surface cooling) after cardiac arrest. Patients were cooled to 32-34°C for 12 to 24 hrs. Last year the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation (ILCOR) recommended cooling for unconscious patients after out-of-hospital cardiac arrest from ventricular fibrillation.

Crit Care Med 2004;32:897-899

The use of mild hypothermia for the treatment of neurologic injury after resuscitation from out-of-hospital cardiac arrest has now been endorsed by the International Liaison Committee on Resuscitation on the basis of supportive evidence from two prospective, randomized, controlled clinical trials. Patients who remain unconscious after resuscitation from cardiac arrest (where the initial cardiac rhythm is ventricular fibrillation) should now receive 12-24 hrs of hypothermia (33°C) as part of their routine care in the intensive care unit.