Clinical Trial of Induced Hypothermia in Comatose Survivors of Out-of-Hospital Cardiac Arrest,☆☆,

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Abstract

Study objective: To examine the effects of moderate hypothermia (33° C), induced by surface cooling in the ED and maintained for 12 hours in the ICU, on patients with anoxic brain injury after out-of-hospital cardiac arrest. Methods: We conducted the study in a teaching hospital in Melbourne, Victoria, Australia. Participants were 22 adults who remained unconscious after return of spontaneous circulation following out-of-hospital cardiac arrest. This treatment group was studied prospectively, and a control group of 22 similar patients was studied by retrospective chart review. Moderate hypothermia (33° C) was induced in the ED by means of surface cooling and maintained for 12 hours in the ICU with rewarming to normothermia over 6 hours; control patients were maintained at normothermia. Results: There were no significant adverse effects of induced hypothermia. Cardiovascular changes included decreased pulse rate, but there were no significant differences in mean arterial blood pressure between the two groups. Small increases in serum potassium and decreases in pH at 18 hours in the hypothermic patients compared with normothermic controls were of no clinical significance. There were no septic complications. There was a significant increase in the number of patients with good outcome (Glasgow Outcome Coma Scale category 1 or 2) with induced hypothermia (11 of 22, versus 3 of 22 for normothermic controls; P<.05), and the mortality rate was significantly lower (10 of 22 versus 17 of 22; P<.05). Conclusion: Compared with historical normothermic controls, outcome was significantly improved and there was no increase in complications when moderate hypothermia was induced in comatose survivors of out-of-hospital cardiac arrest and maintained for 12 hours. Larger, prospective, randomized, controlled studies of induced moderate hypothermia in comatose survivors of out-of-hospital cardiac arrest are warranted. [Bernard SA, Jones BM, Horne MK: Clinical trial of induced hypothermia in comatose survivors of out-of-hospital cardiac arrest. Ann Emerg Med August 1997;30:146-153.]

Section snippets

INTRODUCTION

Patients who remain unconscious after resuscitation from out-of-hospital cardiac arrest have a poor prognosis.1 It is believed that part of the anoxic neurologic injury occurs after the return of spontaneous circulation (ROSC),2 and considerable research has been conducted on therapies that might ameliorate this “reperfusion injury.”3, 4, 5

The findings of animal studies of cerebral anoxia have suggested that moderate induced hypothermia (IH), applied shortly after ROSC, may improve neurologic

MATERIALS AND METHODS

Dandenong Hospital is a 380-bed teaching hospital in the south-east metropolitan area of Melbourne, Victoria, Australia, with a catchment population of approximately 400,000. The EMS system is two tiered: ambulances carry either qualified ambulance officers with defibrillation skills or paramedics with advanced life support (ALS) skills. Paramedics perform all ALS procedures according to protocol, without on-line medical direction. Patients who do not demonstrate ROSC despite ALS in the field

RESULTS

The clinical details of both groups of patients are shown in Table 1. These data suggest that the two groups were comparable at study entry, with no significant differences in age, sex, or time from collapse to ROSC. The two groups had similar incidences of witnessed collapse, bystander CPR, and VF as the presenting rhythm. The depth of coma in the ED, as shown by the number of patients with unreactive pupils and lack of response to a painful stimulus, suggests that the degree of anoxic brain

DISCUSSION

Patients who sustain prehospital cardiac arrest have a poor prognosis, with only 2% to 10% returning home to independent living.13 Many patients remain unconscious after ROSC, and this anoxic brain injury accounts for almost half of the deaths that occur after hospital admission.1, 14, 15

Evidence suggests that part of the neurologic injury (the so-called reperfusion injury) occurs after ROSC, and this has been extensively reviewed.2, 3, 4, 5, 16 The major mechanism of injury is thought to be

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    From the Department of Intensive Care, Dandenong Hospital,* and the Department of Neurosciences, Monash Medical Centre, Southern Health Care Network, Victoria, Australia.

    ☆☆

    Reprint no.47/1/83243

    Address for reprints: Dr Stephen Bernard, The Intensive Care Unit, Dandenong Hospital, David St, Dandenong, Victoria, Australia 3175, 61-3-9791-6000, Fax 61-3-9797-8378

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