Table 2.
Randomized controlled trials assessing neurologic outcomes after cardiac arrest—completed trials.
| Trial name | Study design | Treatment group | Control group | Outcome measure | Results | Reference |
|---|---|---|---|---|---|---|
| Calcium channel blockers | ||||||
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| Effects of nimodipine on cerebral blood flow and cerebrospinal fluid pressure after cardiac arrest: correlation with neurologic outcome | Randomized, double-blind study | Nimodipine IV 0.25 mcg/kg/min (N = 25) |
Placebo (N = 26) |
Primary outcome: CBF measured by Xenon CT Secondary outcomes: ICP, neurological disability |
Higher CBF in nimodipine group in first 4 hours after arrest (P < 0.05) but no difference at 24 hours. No difference in neurological outcomes | Forsman et al., Anesth Analg 1989 [64] |
| Neuropsychological sequelae of cardiac arrest | 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 = 35) |
Placebo (N = 33) |
Primary outcome: 3- and 12-month neuropsychological and cognitive batteries | No difference in neuropsychological or cognitive outcome between groups | Roine et al., JAMA 1992 [65] |
| A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrest | Randomized, double-blind, placebo-controlled, multicenter study | Lidoflazine 1 mg/kg loading dose then 0.25 mg/kg at 8 and 16 hours after resuscitation (N = 259) |
Placebo (N = 257) |
Primary outcome: Pittsburgh Cerebral Performance Scale at 6 months Secondary outcomes: mortality, complications |
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 | Roine et al., JAMA 1990 [67] |
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| Neuroprotective | ||||||
|
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| Coenzyme Q 10 combined with mild hypothermia after cardiac arrest: a preliminary study | Randomized, placebo-controlled, double-blind, single-center study of out-of-hospital cardiac arrest | Hypothermia 35-36°C × 24 hours + Coenzyme Q 10 250 mg PO × 1 then 150 mg PO TID (N = 25) |
Hypothermia 35-36°C × 24 hours + Placebo (N = 24) |
Primary outcome: survival to ICU discharge Secondary outcomes: 3-month survival, 3-month GOS, S100 levels |
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 | Damian et al., Circulation 2004 [68] |
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| Thrombolytics | ||||||
|
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| A pilot randomized trial of thrombolysis in cardiac arrest (the TICA trial) | Randomized, double-blind, placebo controlled, single-center, feasibility trial for out-of-hospital cardiac arrest | Tenecteplase 50 mg IV × 1 (N = 19) |
Placebo (N = 16) |
Primary outcome: ROSC Secondary outcomes: survival to ED, ICU and hospital discharge |
ROSC in 42% of tenecteplase and 6% of placebo group. No difference in survival to hospital discharge | Fatovich et al., Resuscitation 2004 [69] |
| 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 | Böttiger et al., NEJM 2008 [70] |
|
| ||||||
| Steroids and pressors | ||||||
|
| ||||||
| Vasopressin, epinephrine, and corticosteroids for In-hospital cardiac arrest | Randomized, double-blind, placebo-controlled, single-center study | Vasopressin 20 IU IV + epinephrine 1 mg IV + methylprednisolone 40 mg IV followed by hydrocortisone (N = 48) |
Epinephrine + placebo (N = 52) |
Primary outcome: ROSC, survival to discharge Secondary outcomes: blood pressure after CPR, organ failure-free days, discharge Glasgow-Pittsburg cerebral performance scale |
More ROSC in treatment group (81% versus 52%, P = 0.003) and more survival to discharge (19% versus 4%, P = 0.02) | Mentzelopoulos et al., Arch Intern Med 2009 [71] |
|
| ||||||
| Pressors | ||||||
|
| ||||||
| 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 | Brown et al., NEJM 1992 [72] |
| Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospital | Randomized, double-blind, prospective, single-center study | Repeated epinephrine 5 mg IV (N = 271) |
Repeated epinephrine 1 mg IV (N = 265) |
Primary outcome: ROSC Secondary outcomes: admission to the hospital, discharge, cerebral performance category at discharge and 6 months |
No difference in ROSC, admission, discharge, or 6-month neurological outcomes | Choux et al., Resuscitation 1995 [73] |
| 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 | Lindner et al., Lancet 1997 [75] |
| High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapy | Randomized, controlled, single-blind, multicenter study of patients who had failed on standard dose of epinephrine 0.5–1.0 mg IV | Epinephrine 0.1 mg/kg IV up to 4 doses (N = 78) |
Epinephrine 0.01 mg/kg IV up to 4 doses (N = 62) |
Primary outcome: improvement in cardiac rhythm or ROSC Secondary outcomes: GCS at 6, 24, and 72 hours |
No differences in ROSC, survival, or neurologic function between groups | Sherman et al., Pharmacotherarpy 1997 [76] |
| 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 (M = 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 | Gueugniaud et al., NEJM 1998 [77] |
| Vasopressin versus epinephrine for in hospital cardiac arrest: a randomized controlled trial | Randomized, controlled, triple-blind, multicenter study of in-hospital cardiac arrest for asystole, PEA, or refractory ventricular fibrillation | Vasopressin 40 IU IV (first pressor) (N = 104) |
Epinephrine 1 mg IV (first pressor) (N = 96) |
Primary outcome: survival for 1 hour Secondary outcomes: survival to hospital discharge, modified mini-mental state exam at discharge, cerebral performance score at discharge, ROSC, adverse events |
No difference in survival at 1 hour or survival to hospital discharge. No difference in mini-mental state exam scores or cerebral performance scores | Stiell et al., Lancet 2001 [78] |
| 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 | Wenzel et al., NEJM 2004 [79] |
| 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 | Gueugniaud et al., NEJM 2008 [80] |
|
| ||||||
| Magnesium | ||||||
|
| ||||||
| Randomised trial of magnesium in in-hospital cardiac arrest (MAGIC trial) | Randomized, placebo-controlled, single-center study of cardiac arrest in the ICU or general ward | Magnesium 2 g IV bolus then 8 g over 24 hours (N = 76) |
Placebo (N = 80) |
Primary outcome: ROSC Secondary outcomes: 24-hour survival, survival to hospital discharge, GCS, and discharge Karnofsky |
No difference in ROSC, 24-hour survival, survival to discharge, or GCS | Thel et al., Lancet 1997 [81] |
| Magnesium in cardiac arrest (the MAGIC trial) | Randomized, double-blind, placebo-controlled, single-center study of out-of-hospital cardiac arrest | MgSO4 5 g IV × 1 (N = 31) |
Placebo (N = 36) |
Primary outcome: ECG rhythm 2 minutes after drug, ROSC Secondary outcomes: survival to ED, ICU, and hospital discharge |
No differences in ROSC or survival | Fatovich et al., Resuscitation 1997 [82] |
| Magnesium sulfate in the treatment of refractory ventricular fibrillation in the prehospital setting | Randomized, double-blind, placebo-controlled, multicenter study of prehospital ventricular fibrillation refractory to 3 shocks | MgSO4 2 g IV × 1 (N = 58) |
Placebo (N = 58) |
Primary outcome: ROSC Secondary outcomes: admission to hospital, hospital discharge |
No difference in ROSC, survival to admission or discharge | Allegra et al., Resuscitation 2001 [83] |
| A randomized trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillation | Randomized, double-blind, placebo-controlled trial of ventricular fibrillation refractory to 3 shocks | MgSO4 2–4 g IV × 1 (N = 52) |
Placebo (N = 53) |
Primary outcome: ROSC Secondary outcome: hospital discharge |
No differences in ROSC or survival to discharge | Hassan et al., Emerg Med J 2002 [84] |
| 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 | Longstreth et al., Neurology 2002 [85] |
|
| ||||||
| Insulin | ||||||
|
| ||||||
| Intravenous glucose after out-of-hospital cardiopulmonary arrest: a community-based randomized trial | Randomized, single-center controlled study | 5% dextrose (D5W) infusion (N = 374) |
0.45 saline infusion (N = 374) |
Primary outcome: command following or comprehensible speech Secondary outcomes: survival to hospital admission and discharge |
No difference in neurological outcomes, or survival to admission or discharge | Longstreth et al., Neurology 1993 [86] |
| Strict versus moderate glucose control after resuscitation from ventricular fibrillation | Randomized, controlled, multicenter study of out-of-hospital ventricular fibrillation cardiac arrest | Strict glucose control (4–6 mmol/L) with insulin infusion × 48 hours (N = 39) |
Moderate glucose control (6–8 mmol/L) with insulin infusion × 48 hours (N = 51) |
Primary outcome: 30-day all-cause mortality after ROSC Secondary outcomes: neuron-specific enolase levels at 24 and 48 hours |
No difference in 30-day mortality | Oksanen et al., Intensive Care Med 2007 [87] |
|
| ||||||
| Hypothermia | ||||||
|
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| Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia | Randomized, controlled, single-blind, prospective study | Hypothermia 33°C × 12 h (N = 43) |
Normothermia 37°C (N = 34) |
Primary outcome: discharge disposition Secondary outcomes: adverse events, hemodynamic parameters |
Good discharge disposition in 49% of treatment group compared to 26% of normothermia group (P = 0.046). No difference in adverse events | Bernard et al., NEJM 2002 [88] |
| 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 | 2 L 4°C normal saline infusion (N = 63) |
Standard care (N = 62) |
Primary outcome: esophageal temperature, adverse events Secondary outcomes: awakening, hospital discharge |
Significant differences in temperature between groups (P < 0.001). No difference in awakening or hospital discharge | Kim et al., Circulation 2007 [90] |
| 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 | Castrén et al., Circulation 2010 [92] |
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| Chest compressions | ||||||
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| 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) |
Standard CPR (N = 33) |
Primary outcome: ROSC Secondary outcomes: 24-hour survival, hospital discharge, GCS at 24 hours |
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) | Cohen et al., NEJM 1993 [93] |
| The Ontario Trial of Active Compression-Decompression Cardiopulmonary Resuscitation for In-Hospital and Prehospital Cardiac Arrest |
Randomized, single-blind, multicenter controlled trial of prehospital and in-hospital cardiac arrest | Active compression-decompression CPR using a suction device (N = 906) |
Standard CPR (N = 878) |
Primary outcome: survival for 1 hour Secondary outcome: survival to hospital discharge, modified mini-mental state exam, cerebral performance scale |
No differences in survival at 1 hour, survival until hospital discharge or mini-mental state exam for either prehospital or in-hospital arrest | Stiell et al., JAMA 1996 [94] |
| Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth ventilation | Randomized controlled study of out-of-hospital cardiac arrest | Bystander chest compression plus mouth to mouth resuscitation (N = 279) |
Bystander chest compressions alone (N = 241) |
Primary outcome: survival to hospital discharge Secondary outcomes: admission to the hospital, neurological status |
Similar outcome with bystander chest compressions alone versus chest compressions with mouth to mouth | Hallstrom et al., NEJM 2000 [95] |
| Constant flow insufflations of oxygen as the sole mode of ventilation during out-of-hospital cardiac arrest | Randomized, controlled study of out-of-hospital cardiac arrest | Constant flow insufflations of oxygen (N = 487) |
Standard endotracheal intubation and mechanical ventilation (N = 457) |
Primary outcome: survival to ICU discharge Secondary outcomes: ROSC, survival to hospital admission, spO2 > 70% |
No difference in ROSC, hospital admission or ICU discharge. Higher O2 sats in continuous flow insufflation group | Bertrand et al., Intensive Care Med 2006 [96] |
| Compression-only CPR or standard CPR in out-of-hospital cardiac arrest | Randomized, controlled, multicenter study of out-of-hospital cardiac arrest | Compression only CPR (N = 620) |
Standard CPR (N = 656) |
Primary outcome: 30 day survival Secondary outcomes: 1 day survival, ROSC, survival to hospital discharge |
Similar 30-day survival, 1-day survival and survival to hospital discharge | Svensson et al., NEJM 2010 [97] |
| CPR with chest compression alone or with rescue breathing | Randomized, controlled, multicenter study of out-of-hospital cardiac arrest | Chest compressions alone (N = 981) |
Chest Compressions + Rescue breathing (2 breaths to 15 chest compressions) (N = 960) |
Primary outcome: survival to hospital discharge Secondary outcomes: discharge cerebral performance Score, ROSC |
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) | Rea et al., NEJM 2010 [98] |
| 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 |
No difference in survival with good mRS | Aufderheide et al., NEJM 2011 [99] |
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| Adenosine antagonist | ||||||
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| 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 | Abu-Laban et al., Lancet 2006 [100] |
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| Fluid management | ||||||
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| Capillary leakage in postcardiac arrest survivors during therapeutic hypothermia: a prospective, randomized study | Randomized, controlled study | 7.2% hypertonic saline with 6% poly starch solution × 24 hours (N = 10) |
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] |
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| Barbiturate | ||||||
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| 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] |
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| Calcium | ||||||
|
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| Calcium chloride: reassessment of use in asystole | Randomized, double-blind, placebo-controlled study in prehospital asystolic cardiac arrest refractory to epinephrine, bicarbonate, and atropine | Calcium chloride (N = 18) |
Placebo (N = 14) |
Primary outcome: ROSC Secondary outcome: hospital discharge |
No difference in ROSC | Stueven et al., Ann Emerg Med 1984 [103] |
| The effectiveness of calcium chloride in refractory electromechanical dissociation | Randomized, blinded, placebo-controlled study of prehospital PEA arrest refractory to epinephrine and bicarbonate | Calcium chloride (N = 48) |
Placebo (N = 42) |
Primary outcome: ROSC Secondary outcomes: survival to hospital discharge |
No difference in ROSC but subgroup of patients with widened QRS did have more ROSC in calcium group (P = 0.028) | Stueven et al., Ann Emerg Med 1985 [104] |
| Lack of effectiveness of calcium chloride in refractory asystole |
Randomized, blinded, placebo controlled study of prehospital asystolic cardiac arrest refractory to epinephrine, bicarbonate, and atropine |
Calcium chloride (N = 39) |
Placebo (N = 34) |
Primary outcome: ROSC Secondary outcomes: survival to hospital discharge |
No difference in ROSC or hospital discharge | Stueven et al., Ann Emerg Med 1985 [105] |
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| Sodium bicarbonate | ||||||
|
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| Buffer therapy during out-of-hospital cardiopulmonary resuscitation | Randomized, double-blind, placebo-controlled study of out-of-hospital asystole or ventricular fibrillation refractory to first defibrillation attempt | Sodium bicarbonate 250 mL IV × 1 (N = 245) |
Placebo (N = 257) |
Primary outcome: survival to ICU admission, survival to hospital discharge | No difference in survival to ICU admission or hospital discharge | Dybvik et al., Resuscitation 1995 [106] |
| Sodium bicarbonate improves outcome in prolonged prehospital cardiac arrest | Randomized, double-blind, placebo-controlled trial of prehospital cardiac arrest | Sodium bicarbonate (1 meq/kg) IV × 1 (N = 175) |
Placebo (N = 155) |
Primary outcome: survival to ED Secondary outcomes: ROSC |
No difference in survival to ED admission or ROSC. Better survival with bicarbonate in the prolonged (>15 minute) arrest group (P = 0.007) |
Vukmir and Katz,Am J Emerg Med 2006 [107] |
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| Hemofiltration | ||||||
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| High-volume hemofiltration after out-of-hospital cardiac arrest: a randomized study | Randomized, controlled trial of out-of-hospital ventricular fibrillation or asystole cardiac arrest | Tier 1: hemofiltration (200 mL/kg/h) over 8 hours (N = 20) Tier 2: hemofiltration plus hypothermia to 32°C × 24 hours (N = 22) |
Standard care (N = 19) |
Primary outcome: survival at 6 months Secondary outcome: intractable shock, Pittsburgh cerebral performance scale |
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 | Laurent et al., J Am Coll Cardiol 2005 [108] |
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| Rhythm analysis | ||||||
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| Early versus later rhythm analysis in patients with out-of-hospital cardiac arrest | Cluster randomized, controlled, multicenter study of out-of-hospital cardiac arrest | Early rhythm analysis: 30–60 seconds of EMS CPR followed by ECG analysis (N = 5290) |
Later rhythm analysis: 180 seconds of EMS CPR followed by ECG analysis (N = 4643) |
Primary outcome: survival to hospital discharge with mRS 0–3 Secondary outcomes: survival to discharge, survival to hospital admission, ROSC |
No difference in outcome between a brief and longer period of CPR before ECG analysis of rhythm | Stiell et al., NEJM 2011 [109] |