Table 2: Randomized controlled trials assessing neurologic outcomes after cardiac arrest—completed trials.

Trial nameStudy designTreatment groupControl groupOutcome measureResultsReference

Calcium channel blockers

Effects of nimodipine on cerebral blood flow and cerebrospinal fluid pressure after cardiac arrest: correlation with neurologic outcomeRandomized, double-blind studyNimodipine 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 outcomesForsman et al.,
Anesth Analg 1989 [64]
Neuropsychological sequelae of cardiac arrest Randomized, double-blind, placebo-controlled, study of out-of-hospital ventricular fibrillationNimodipine 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 batteriesNo difference in neuropsychological or cognitive outcome between groupsRoine et al.,
JAMA 1992 [65]
A randomized clinical study of a calcium-entry blocker (lidoflazine) in the treatment of comatose survivors of cardiac arrestRandomized, double-blind, placebo-controlled, multicenter studyLidoflazine 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 groupsBrain Resuscitation Clinical Trial II Study Group, NEJM 1991 [66]
Nimodipine after resuscitation from out-of-hospital ventricular fibrillation: a placebo-controlled, double-blind, randomized trialRandomized, double-blind, placebo-controlled, study of out-of-hospital ventricular fibrillationNimodipine 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 seizuresRoine et al.,
JAMA 1990 [67]

Neuroprotective

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 arrestHypothermia 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]

Thrombolytics

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 arrestTenecteplase 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 dischargeFatovich et al., Resuscitation 2004 [69]
Thrombolysis during resuscitation for out-of-hospital cardiac arrestRandomized, double-blind, controlled, multicenter study of out-of-hospital cardiac arrestTenecteplase 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 arrestRandomized, double-blind, placebo-controlled, single-center studyVasopressin 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 hospitalRandomized, double-blind, prospective, multi-center studyEpinephrine 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 statusBrown et al., NEJM 1992 [72]
Standard doses versus repeated high doses of epinephrine in cardiac arrest outside the hospitalRandomized, double-blind, prospective, single-center studyRepeated 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 outcomesChoux et al., Resuscitation 1995 [73]
A randomized, double-blind comparison of methoxamine and epinephrine in human cardiopulmonary arrestRandomized, double-blind, single-center studyMethoxamine 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 dischargePatrick et al.,
Am J Respir Crit Care Med 1995 [74]
Randomised comparison of epinephrine and vasopressin in patients with out-of-hospital ventricular fibrillationRandomized, double-blind, single-center, controlled study of out-of-hospital ventricular fibrillation patients who failed defibrillationVasopressin 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 dischargeLindner et al.,
Lancet 1997 [75]
High-dose versus standard-dose epinephrine treatment of cardiac arrest after failure of standard therapyRandomized, controlled, single-blind, multicenter study of patients who had failed on standard dose of epinephrine 0.5–1.0 mg IVEpinephrine 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 groupsSherman et al., Pharmacotherarpy 1997 [76]
A comparison of repeated high doses and repeated standard doses of epinephrine for cardiac arrest outside the hospitalRandomized, controlled, prospective multicenter studyEpinephrine 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 statusGueugniaud et al., NEJM 1998 [77]
Vasopressin versus epinephrine for in hospital cardiac arrest: a randomized controlled trialRandomized, controlled, triple-blind, multicenter study of in-hospital cardiac arrest for asystole, PEA, or refractory ventricular fibrillationVasopressin 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 scoresStiell et al.,
Lancet 2001 [78]
A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitationRandomized, 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 performanceWenzel et al.,
NEJM 2004 [79]
Vasopressin and epinephrine versus epinephrine alone in cardiopulmonary resuscitationRandomized, controlled, multicenter trialEpinephrine 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 recoveryGueugniaud 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 wardMagnesium 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 GCSThel 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 arrestMgSO4 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 settingRandomized, double-blind, placebo-controlled, multicenter study of prehospital ventricular fibrillation refractory to 3 shocksMgSO4 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 dischargeAllegra et al.,
Resuscitation 2001 [83]
A randomized trial to investigate the efficacy of magnesium sulphate for refractory ventricular fibrillationRandomized, double-blind, placebo-controlled trial of ventricular fibrillation refractory to 3 shocksMgSO4 2–4 g IV × 1
(N = 52)
Placebo
(N = 53)
Primary outcome: ROSC
Secondary outcome: hospital discharge
No differences in ROSC or survival to dischargeHassan et al.,
Emerg Med J 2002 [84]
Randomized clinical trial of magnesium, diazepam, or both after out-of-hospital cardiac arrestRandomized, double-blind, placebo-controlled factorial design studyTier 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 groupsLongstreth et al., Neurology 2002 [85]

Insulin

Intravenous glucose after out-of-hospital cardiopulmonary arrest: a community-based randomized trialRandomized, single-center controlled study5% 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 dischargeLongstreth et al., Neurology 1993 [86]
Strict versus moderate glucose control after resuscitation from ventricular fibrillationRandomized, controlled, multicenter study of out-of-hospital ventricular fibrillation cardiac arrestStrict 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 mortalityOksanen et al., Intensive Care Med 2007 [87]

Hypothermia

Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermiaRandomized, controlled, single-blind, prospective studyHypothermia 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 eventsBernard et al., NEJM 2002 [88]
Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrestRandomized, controlled, single-blind, multicenter, prospective studyHypothermia 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 ratesThe 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 salineRandomized, controlled, safety and feasibility study of out-of-hospital cardiac arrest2 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 dischargeKim et al.,
Circulation 2007 [90]
Prehospital therapeutic hypothermia for comatose survivors of cardiac arrest: a randomized controlled trialRandomized controlled trail of out-of-hospital cardiac arrest4°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 arrestIntra-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]

Chest compressions

A comparison of active compression-decompression cardiopulmonary resuscitation with standard cardiopulmonary resuscitation for cardiac arrests occurring in the hospitalRandomized, controlled, single center studyCPR 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 arrestActive 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 arrestStiell et al.,
JAMA 1996 [94]
Cardiopulmonary resuscitation by chest compression alone or with mouth-to-mouth ventilationRandomized controlled study of out-of-hospital cardiac arrestBystander 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 mouthHallstrom et al.,
NEJM 2000 [95]
Constant flow insufflations of oxygen as the sole mode of ventilation during out-of-hospital cardiac arrestRandomized, controlled study of out-of-hospital cardiac arrestConstant 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 groupBertrand et al., Intensive Care Med 2006 [96]
Compression-only CPR or standard CPR in out-of-hospital cardiac arrestRandomized, controlled, multicenter study of out-of-hospital cardiac arrestCompression 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 dischargeSvensson et al.,
NEJM 2010 [97]
CPR with chest compression alone or with rescue breathingRandomized, controlled, multicenter study of out-of-hospital cardiac arrestChest 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 arrestRandomized, controlled, double-blinded, multicenter study of out-of-hospital cardiac arrestImpedance 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]

Adenosine antagonist

Aminophylline in bradyasystolic cardiac arrest: a randomized placebo-controlled trialRandomized, placebo-controlled, double-blind, multicenter study of asystole and PEA arrest unresponsive to epinephrine and atropineAminophylline 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 differentAbu-Laban et al., Lancet 2006 [100]

Fluid management

Capillary leakage in postcardiac arrest survivors during therapeutic hypothermia: a prospective, randomized studyRandomized, controlled study7.2% 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 edemaHeradstveit et al., Scand J Trauma Resusc Emerg Med 2010 [101]

Barbiturate

Randomized clinical study of thiopental loading in comatose survivors of cardiac arrestRandomized, controlled, multicenter studyThiopental 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 groupsBrain Resuscitation Clinical Trial I Study Group.
NEJM 1986 [102]

Calcium

Calcium chloride: reassessment of use in asystoleRandomized, double-blind, placebo-controlled study in prehospital asystolic cardiac arrest refractory to epinephrine, bicarbonate, and atropineCalcium 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 dissociationRandomized, blinded, placebo-controlled study of prehospital PEA arrest refractory to epinephrine and bicarbonateCalcium 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 dischargeStueven et al.,
Ann Emerg Med 1985 [105]

Sodium bicarbonate

Buffer therapy during out-of-hospital cardiopulmonary resuscitationRandomized, double-blind, placebo-controlled study of out-of-hospital asystole or ventricular fibrillation refractory to first defibrillation attemptSodium bicarbonate 250 mL IV × 1
(N = 245)
Placebo
(N = 257)
Primary outcome: survival to ICU admission, survival to hospital dischargeNo difference in survival to ICU admission or hospital dischargeDybvik et al.,
Resuscitation 1995 [106]
Sodium bicarbonate improves outcome in prolonged prehospital cardiac arrestRandomized, double-blind, placebo-controlled trial of prehospital cardiac arrestSodium 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]

Hemofiltration

High-volume hemofiltration after out-of-hospital cardiac arrest: a randomized studyRandomized, controlled trial of out-of-hospital ventricular fibrillation or asystole cardiac arrestTier 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 outcomeLaurent et al.,
J Am Coll Cardiol 2005 [108]

Rhythm analysis

Early versus later rhythm analysis in patients with out-of-hospital cardiac arrestCluster randomized, controlled, multicenter study of out-of-hospital cardiac arrestEarly 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 rhythmStiell et al.,
NEJM 2011 [109]