No difference in 6-month neurological outcome or mortality between groups
Brain Resuscitation Clinical Trial II Study Group, NEJM 1991 [66]
Nimodipine after resuscitation from out-of-hospital ventricular fibrillation: a placebo-controlled, double-blind, randomized trial
Randomized, double-blind, placebo-controlled, study of out-of-hospital ventricular fibrillation
Nimodipine 10 mcg/kg IV then 0.5 mcg/kg/min × 24 hours (N = 75)
Placebo (N = 80)
Primary outcome: survival, 1-year GOS Secondary outcomes: death related to anoxic encephalopathy, GCS at 24 hours and 1 week, 3- and 12-month mini-mental state exam, activities of daily living, Barthel index, neurological exam, seizure, SPECT, myocardial infarction, arrhythmias
No difference in the survival rate, GOS at 3 or 12 months. No difference in minimental state exam, activities of daily living, or seizures
3-month survival was 68% in the treatment group and 29% in the control group (P = 0.0413). There was no significant difference in survival until discharge or GOS outcome
Thrombolysis during resuscitation for out-of-hospital cardiac arrest
Randomized, double-blind, controlled, multicenter study of out-of-hospital cardiac arrest
Tenecteplase 0.5 mg/kg IV (N = 525)
Placebo (N = 525)
Primary outcome: survival at 30 days Secondary outcomes: survival to admission, ROSC, 24-hour survival, survival to discharge, cerebral performance score at discharge
No difference in 30-day survival, hospital admission, ROSC, 24-hour survival, discharge, or neurologic outcome. More intracranial hemorrhages in treatment group
A comparison of standard-dose and high-dose epinephrine in cardiac arrest outside the hospital
Randomized, double-blind, prospective, multi-center study
Epinephrine 0.2 mg/kg IV (N = 648)
Epinephrine 0.02 mg/kg IV (N = 632)
Primary outcome: return of spontaneous circulation (ROSC), admission to the hospital Secondary outcome: cerebral performance scale at admission, and discharge
No difference in ROSC rates, admission, survival, or discharge neurological status
A randomized, double-blind comparison of methoxamine and epinephrine in human cardiopulmonary arrest
Randomized, double-blind, single-center study
Methoxamine 40 mg bolus IV then 40 mg 4 minutes later (N = 77)
Epinephrine 2 mg bolus then 2 mg IV q 4 min (N = 68)
Primary outcome: Mortality and Glasgow-Pittsburgh coma score Secondary outcomes: ROSC, successful resuscitation
No difference in ROSC or neurologic outcome, initial resuscitation, or survival to discharge
Patrick et al., Am J Respir Crit Care Med 1995 [74]
Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillation
Randomized, double-blind, single-center, controlled study of out-of-hospital ventricular fibrillation patients who failed defibrillation
Vasopressin 40 IU IV (N = 20)
Epinephrine 1 mg IV (N = 20)
Primary outcome: survival to admission Secondary outcome: 24-hour survival, survival to discharge, GCS at discharge
No significant difference in survival to admission but more vasopressin patients survived 24 hours (60% versus 20%, P = 0.02). No difference in survival to discharge or GCS at discharge
A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospital
Randomized, controlled, prospective multicenter study
Epinephrine 5 mg IV up to 15 doses at 3-minute intervals (N = 1677)
Epinephrine 1 mg IV up to 15 doses at 3-minute intervals ( = 1650)
Primary outcome: ROSC, admission to the hospital, number of admissions after a single dose of epinephrine, hospital discharge Secondary outcomes: survival, neurological outcome by GCS and cerebral performance scale
Significantly more ROSC in high dose group (40% versus 36% of control group, P = 0.02) and more survival to admission (26.5% versus 23.6% of controls, P = 0.05). No difference in survival to discharge or neurological status
A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation
Randomized, controlled, multicenter study of out-of-hospital cardiac arrest with ventricular fibrillation failing defibrillation, PEA, or asystole
Vasopressin 40 IU IV × 2 doses maximum (N = 589)
Epinephrine 1 mg IV × 2 doses maximum (N = 597)
Primary outcome: survival to hospital admission Secondary outcomes: survival to hospital discharge, cerebral performance score in survivors
No difference in survival to admission among patients with ventricular fibrillation or PEA. Higher rates of hospital admission for asystole in vasopressin group (29% versus 20%, P = 0.02) and hospital discharge (4.7% versus 1.5% with epinephrine, P = 0.04). Patients who received rescue epinephrine after vasopressin had better survival to admission and discharge than the epinephrine alone group. No difference in cerebral performance
Vasopressin and epinephrine versus epinephrine alone in cardiopulmonary resuscitation
Randomized, controlled, multicenter trial
Epinephrine 1 mg IV + Vasopressin 40 IU IV (N = 1442)
Epinephrine 1 mg IV + Placebo (N = 1452)
Primary outcome: Survival to hospital admission Secondary outcomes: ROSC, survival to hospital discharge, good neurological recovery by cerebral performance scale, and GCS, 1-year survival
No differences in survival to admission, ROSC, survival to discharge, 1-year survival, or good neurologic recovery
Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrest
Randomized, double-blind, placebo-controlled factorial design study
Tier 1: magnesium 2 g IV + placebo (N = 75) Tier 2: diazepam 10 mg IV + placebo (N = 75) Tier 3: magnesium 2 g IV + Diazepam 10 g IV (N = 75)
Placebo only (N = 75)
Primary outcome: awakening at 3 months (comprehensible speech and command following) Secondary outcome: days to awakening, days to death, independent at 3 months
No difference in neurological outcome between the 3 groups
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest
Randomized, controlled, single-blind, multicenter, prospective study
Hypothermia 32–34°C × 24 h (N = 137)
Normothermia 37°C (N = 138)
Primary outcome: 6 month neurologic outcome using Pittsburgh cerebral performance scale Secondary outcome: 6-month mortality, complications at 7 days
Hypothermia group had more favorable neurological outcome at 6 months (55% versus 39% of normothermia group, P = 0.009). Less death in hypothermia group (41% versus 55% in normothermia group, P = 0.02). No difference in complication rates
The hypothermia after cardiac arrest study group, NEJM 2002 [89]
Pilot randomized clinical trial of prehospital induction of mild hypothermia in out-of-hospital cardiac arrest patients with a rapid infusion of 4 degrees C normal saline
Randomized, controlled, safety and feasibility study of out-of-hospital cardiac arrest
Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trial
Randomized controlled trail of out-of-hospital cardiac arrest
4°C Ringers solution 30 mL/kg to target temperature 33°C (N = 19)
Conventional fluid therapy (N = 18)
Primary outcome: nasopharyngeal temperature Secondary outcomes: hospital mortality and cerebral performance scale
Lower core temperature in the treatment group (P < 0.001). No difference in safety, mortality, or neurologic outcome
KÄmÄrÄinen et al., Acta Anaesthesiol Scand 2009 [91]
Intra-arrest transnasal evaporative cooling: a randomized, prehospital, multicenter study (PRINCE: pre-rosc intranasal cooling effectiveness)
Randomized, controlled, prospective, single-blind, multicenter study for out-of-hospital arrest
Intra-arrest intranasal cooling with RhinoChill device + cooling at hospital arrival to 34°C (N = 93)
Standard care with cooling at hospital arrival to 34°C (N = 101)
Primary Outcome: adverse events, length of stay, mechanical ventilation days, ROSC, survival to discharge, discharge Pittsburgh cerebral performance scale.
Time to target temperature was shorter in the intranasal cooling group (P = 0.03). No difference in ROSC, survival of admitted patients, or neurologic outcome at discharge
A comparison of active compression-decompression cardiopulmonary resuscitation with standard cardiopulmonary resuscitation for cardiac arrests occurring in the hospital
Randomized, controlled, single center study
CPR using suction device (Ambu CardioPump) (N = 29)
ROSC occurred in 62% of treatment group versus 30% of control group (P < 0.03) and 45% of treatment group survived 24 hours compared to 9% of control group (P < 0.004). GCS at 24 hours was better in the treatment group (P < 0.02)
No difference in survival to hospital discharge or in neurologic outcome. Trend toward improved survival at discharge in those with cardiac cause of arrest and shockable rhythm (P = 0.09)
A trial of an impedance threshold device in out-of-hospital cardiac arrest
Randomized, controlled, double-blinded, multicenter study of out-of-hospital cardiac arrest
Impedance threshold device (ITD) which increasing negative intrathoracic pressure and improves cardiac output (N = 4373)
Sham ITD (N = 4345)
Primary outcome: survival to hospital discharge with mRS 0–3 Secondary outcomes: survival to ED admission, hospital admission and hospital discharge, adverse events
Aminophylline in bradyasystolic cardiac arrest: a randomized placebo-controlled trial
Randomized, placebo-controlled, double-blind, multicenter study of asystole and PEA arrest unresponsive to epinephrine and atropine
Aminophylline 250 mg (N = 486)
Placebo (N = 485)
Primary outcome: ROSC Secondary outcomes: duration of ROSC, survival to admission, survival to discharge, length of stay, 24-hour tachyarrhythmias, 24-hour seizures, 1-year neurologic outcome by GCS, Glasgow-Pittsburgh cerebral and overall performance scales, modified mini-mental state exam, functional status questionnaire
No difference in ROSC. More tachyarrhythmias in the treatment group. Survival to hospital admission and survival to discharge were not different
Standard Fluid (Ringer’s acetate) × 24 hours (N = 9)
Primary outcome: amount of fluid administered in 24 hours Secondary outcome: MRI vasogenic edema
The treatment group required significantly less fluid than the control group. There was no difference in MRI brain edema
Heradstveit et al., Scand J Trauma Resusc Emerg Med 2010 [101]
Barbiturate
Randomized clinical study of thiopental loading in comatose survivors of cardiac arrest
Randomized, controlled, multicenter study
Thiopental 30 mg/kg IV load (N = 131)
Standard therapy (N = 131)
Primary outcome: Pittsburgh cerebral Performance scale at 6 and 12 months Secondary outcomes: best neurological performance ever obtained during followup, time to recovery
No difference in neurological outcome or mortality between groups
Brain Resuscitation Clinical Trial I Study Group. NEJM 1986 [102]
Calcium
Calcium chloride: reassessment of use in asystole
Randomized, double-blind, placebo-controlled study in prehospital asystolic cardiac arrest refractory to epinephrine, bicarbonate, and atropine
Significantly better survival compared to control in hemofiltration group (P = 0.026) and hemofiltration plus hypothermia group (P = 0.018). No difference in 6-month neurologic outcome