Cardiac Arrest Literature Summaries


Nielsen N, et al. Targeted temperature management at 33°C versus 36°C after cardiac arrest. N Engl J Med. 2013 Dec 5;369(23):2197-206. [PMID 24237006]

  • MCRCT without allocation concealment
  • 36 ICUs in Europe and Australia
  • n = 939
  • Patients: unconscious (GCS<8) adults (aged 18y or more) after out-of hospital cardiac arrest of presumed cardiac cause
    — exclusions: interval from ROSC to screening of >240 minutes, unwitnessed arrest with asystole as the initial rhythm, suspected or known acute intracranial hemorrhage or stroke, and a body temperature <30°C
  • Intervention: targeted temperature management at 33°C
  • Comparator: targeted temeperature management at 36°C (“normothermia”)
  • Outcomes:
    — primary outcome: all-cause mortality
    — secondary outcomes: a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale; adverse events reported in day 1 of 7 of ICU stay
  • Results:
    — No difference in outcomes between cooling to T33C compared T36C
    — mortality: 50% versus 48%
    — poor neurological function:  54% versus 52% using the CPC (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P = 0.78); 52% for both groups using the modified Rankin scale
    — results of analyses adjusted for known prognostic factors were similar
    — Hypokalemia was more frequent in  T33°C (19%) vs T36°C (13%) (P=0.02); no other adverse effects had a statistically significant difference
  • Commentary and criticisms:
    — the study included a protocol that clearly delineated their approach for the 26% of patients who had withdrawal of care before hospital discharge
    — neurological prognostication was performed a minimum of 72h after the intervention period ended (unless there was myoclonic status in the first 24h and absent N20 SSEPs)
    — physicians performing neurologic prognostication, assessors of neurologic follow-up and final outcome, study administrators, statisticians, and the authors were blinded
    — both groups underwent gradual rewarming to 37°C at 28h in hourly increments of 0.5°C, and at 36h mandatory sedation was discontinued or tapered
    — neurologically intact survival would have been a better patient-orientated primary outcome, but the authors chose all cause mortality as it is less susceptible to measurement bias
    — the trial was not powered to detect relative risk reductions <20%
    — baseline balance: slightly higher rates of MI and IHd in the T33 group, more diabetes mellitus in the T36 group; similar spread of presumed cause of death
    — modified intention-to-treat analysis (all except those that withdrew consent)
    — unlike the Bernard 2002 and HACA 2002 studies, this trial did not focus on VT/VF arrest patients only
    — following this study unanswered questions include: do certain subgroups of cardiac arrest paitents still benefit from T<36C?

Bernard SA et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med. 2002 Feb 21;346(8):557-63. [PMID 11856794]

  • small pseudo-randomised (alternate days) trial without allocation concealment
  • n = 77
  • patients: those remained unconscious after resuscitation from OOHCA due to VF
  • intervention: hypothermia = cooled to 33 C within 2 hours and maintained for 12 hrs
  • control: standard care without targeted temperature management
  • outcome: Absolute Risk Reduction (ARR) for death or severe disability of 23%, number needed to treat (NNT) was 4.5
  • commentary and criticisms:
    — no record of baseline neurological status prior to the event
    — no record of GCS on arrival in ED
    — good outcome was defined as home or rehab facility at hospital discharge (rather than a structured assessment)
    — positive outcome of trial would have been lost if 1 patient in good outcome group had a bad outcome

Hypothermia after Cardiac Arrest Study Group. Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med. 2002 Feb 21;346(8):549-56. [PMID 11856793]

  • small MCRCT without allocation concealment
  • n = 136
  • patients: out-of-hospital cardiac arrest that remain unconscious
  • intervention: cooled to 32-34 C for 24hrs within 4 hrs
  • comparator: standard care without targetted temperature management
  • outcome: ARR for unfavourable neurological outcome at 6 months (using a grading system) of 24%, and NNT of 4
  • commentary and criticisms:
    — no active temperature control — usual care group were not actually normothermic, they tended to be hyperthermic
    — trial stopped early
    — only 8% of screened ED patients were included

Bernard SA et al. Induction of therapeutic hypothermia by paramedics after resuscitation from out-of-hospitalventricular fibrillation cardiac arrest: a randomized controlled trial. Circulation. 2010 Aug 17;122(7):737-42. [PMID 20679551]

  • RICH Investigators – Rapid infusion with Ice Cold Hartmans
  • n = 234
  • patients: out-of-hospital cardiac arrest with an initial rhythm of VF
    — exclusions: not intubated, previously dependent on others for ADLs before the cardiac arrest, already hypothermic (<34C), or pregnant women
  • Intervention: prehospital rapid infusion of 2L of ice-cold Hartmans (with midazolam and pancuronium) then a further 2L in ED vs standard cooling to 33 C for 24 hours
  • Comparison: cooling after hospital admission
  • Outcome: Functional status at hospital discharge. Patients who were discharged directly home or to a rehab facility were considered to have a favorable outcome. Patients who died or were discharged to a long-term nursing facility, either conscious or unconscious, were considered unfavorable outcome.
  • Results: no difference favourable outcome 47% in treatment group vs 53% in hospital cooling group, RR of favourable vs non-favourable outcome = 0.89 (p 0.433)
  • Commentary and criticisms:
    — patient were 0.5 C colder who were treated in the field but there was no difference between groups @ 30 min
    — mean decrease in core temperature was 0.8 degrees C (P=0.01)
    — Patients allocated to paramedic cooling received a median of almost 2L (1900ml)
    — study stopped early due to interim analysis predicting no difference
    — short transporation times in this study (prehospital hypothermia might be beneficial if long prehospital transport times)
    — should rapid infusion occur before or after ROSC?


Kilgannon JH et al. Association between arterial hyperoxia following resuscitation from cardiac arrest and in-hospital mortality. JAMA. 2010 Jun 2;303(21):2165-71 [PMID 20516417]

  • hypothesis = that post-resuscitation hyperoxia is associated with increased mortality.
  • too little oxygen -> hypoxic brain injury
  • too much oxygen -> O2 radical production triggering cell injury and apoptosis
  • multicenter cohort study
  • 120 hospitals
  • n = 6326 patients
  • inclusion criteria: adults, nontraumatic cardiac arrest, CPR within 24 hours prior to ICU arrival, ABG analysis performed within 24 hours following ICU arrival
  • patients divided into 3 groups based of PaO2 – hyperoxia (>300mmHg), hypoxia (significantly higher in-hospital mortality (OR = 1.8)
  • not cooled


Zandbergen EG, de Haan RJ, Stoutenbeek CP, Koelman JH, Hijdra A. Systematic review of early prediction of poor outcome in anoxic-ischaemic coma. Lancet. 1998 Dec 5;352(9143):1808-12. [PMID 9851380]

  • 33 studies
  • 14 prognostic variables looked at
  • 3 variable had a specificity of 100% for poor outcome:
    1. absent pupillary reflexes @ day 3
    2. absent motor response to pain (worse than withdrawal) on day 3
    3. bilateral absence of early cortical SSEP within the first week
  • other poor prognostic factors = an isoelectric EEG, burst suppression, myoclonus on stimulation.

Fugate JE et al. Predictors of neurologic outcome in hypothermia after cardiac arrest. Ann Neurol. 2010 Dec;68(6):907-14. [PMID 21061401]

  • the predictive value of neurological prognostic indicators for patients treated with hypothermia after surviving cardiac arrest is unknown.
  • prospective co-hort study
  • single center study (US)
  • n = 192 (103 hypothermia, 89 nonhypothermia)
  • June 2006 to October 2009
  • information gathered at 72 hours:
    — clinical examination (pupillary light reflex, corneals, extensor or absent motor response)
    — SSEP’s
    — EEG
  • outcome measure: in-hospital mortality
    -> clinical examination (brainstem reflexes, motor response, myoclonus) remained an accurate predictor after therapeutic hypothermia
    -> myoclonic status invariably associated with death
    -> malignant EEG patterns (burst-suppression, generalized suppression, status epilepticus and non-reactivity) associated with death.
    -> serum neuron specific enolase (NSE) > 33ng measured at 1-3 days after cardiac arrest are associated with a poor outcome but has a high false-positive rate.
    -> CT showing global cerebral oedema associated with death.
    -> sedative medication and liver/renal dysfunction can alter examination accuracy
  • Strengths
    — hmmm…
  • Weaknesses
    — single center
    — non-hypothermia group (non-VF or inhospital)
    — residual sedatives may have compounded examination findings


Hillman K et al. Introduction of the medical emergency team (MET) system: a cluster-randomised controlled trial. Lancet. 2005 Jun 18-24;365(9477):2091-7. [PMID 15964445]

  • multi-centre
  • cluster randomised control trial
  • 23 Australian Hospitals (12 MET trained and implemented, 11 did not)
  • training (2 months), implementation (4 months), study period (6 months)
  • n = 741,744
  • primary outcomes: incidence of cardiac arrests, unplanned admissions to intensive care units and death.
    -> significant increases in emergency team calls
    -> no significant change in cardiac arrest, unplanned ICU admissions or deaths
  • problems:
    -> observations were not frequent enough
    -> MET teams were not called when poor observations were measured
    -> there was a substantial decreased in unexpected deaths in both groups during the study period (contamination) -> 30% reduction!
    -> under powered as base line event rate was assumed to by 30 per 1000 when it was actually 7 per 1000.
  • Post-hoc Analysis of the MERIT Study (Critical Care Med. 2009 Jan;37(1):349-50):
    — examination of the relationship between early emergency teams calls and incidence of serious adverse events (not associated with cardiac arrest or death)
    -> as the proportion of early emergency teams calls increases -> the rate of cardiac arrest and unexpected death decreases.


Wenzel V et al. A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation. N Engl J Med. 2004 Jan 8;350(2):105-13. [PMID 14711909]

  • triple blinded multi-centre randomised trial
  • n = 1219
  • initial vasopressin (40IU) vs adr (1mg) then increments of epinephrine/ adrenaline
    -> rates of admission unchanged
    -> higher survival to hospital admission for patients resuscitated with vasopressin from asystole

Olasveengen TM, Sunde K, Brunborg C, Thowsen J, Steen PA, Wik L. Intravenous drug administration during out-of-hospital cardiac arrest: a randomized trial. JAMA. 2009 Nov 25;302(20):2222-9 [PMID 19934423]

  • RCT
  • Norwegian
  • 2003-2008
  • n = 851
  • ACLS with IV drug administration vs ACLS and no drug administration
  • primary outcome = survival to hospital discharge
  • secondary outcomes = 1 year survival, survival with favourable neurological outcome, hospital admission with ROSC, quality of CPR (chest compression rate, pauses, ventilation rate)
  • inclusion criteria: > 18 years, non-traumatic, OHCA
  • exclusion criteria: cardiac arrest witnessed by ambulance crew, resuscitation initiated by physicians, cardiac arrest induced by anaphylaxis or asthma
    -> increased short term survival in IV drug group
    -> no difference to survival to hospital discharge, quality of CPR or long term survival
  • Weaknesses
    — 3 min of CPR prior to defibrillation in VF
    — 10% of no drugs group received drugs during resuscitation
    — not powered correctly


Rea TD et al. CPR with chest compression alone or with rescue breathing. N Engl J Med. 2010 Jul 29;363(5):423-33 [PMID 20818863]

  • MRCT (Washington and London x 2 sites)
  • chest compressions only vs chest compression + rescue breathing
  • primary outcome: survival to hospital discharge
  • secondary outcomes: favourable neurological outcome, ROSC
  • inclusion criteria: >18 years, OHCA, dispatcher initiated CPR instruction to bystanders
  • exclusion criteria: all ready having CPR, trauma, drowning, asphyxiation, less than 18 yrs, DNR orders
  • n = 1941
    -> no difference in survival
    -> no difference in favourable neurological outcome
    -> trend towards increased survival in chest compression alone group in those who had a cardiac arrest and a shockable rhythm
    -> bystanders more likely to perform CPR than rescue breathing
  • Criticisms
    — one site unable to provide neurological status at discharge!
    — despite having nearly 2000 patient it required 4200 to obtain 80% power

Svensson L et al. Compression-only CPR or standard CPR in out-of-hospital cardiac arrest. N Engl J Med. 2010 Jul 29;363(5):434-42 [PMID 20818864]

  • RCT
  • n = 1276
  • Swedish
  • compression only CPR only vs Standard CPR
  • primary end point = 30 day survival
  • secondary end points = 1 day survival, first detected cardiac rhythm, survival to discharge from hospital
  • inclusion criteria: witnessed, unconsciousness, abnormal or no breathing
  • exclusion criteria: arrest caused by: trauma, airway obstruction, drowning, intoxification, age < 8, difficulty communicating, no CPR started, knowledge of how to perform CPR -> no difference between the groups in all aspects
  • Criticisms
    — some differences between baseline characteristics of groups – standard CPR group (younger)
    — 113 patients assigned to compressions only got ventilation
    — needed 1000 patient in each arm -> only got 600

SOS-KANTO study group. Cardiopulmonary resuscitation by bystanders with chest compression only (SOS-KANTO): an observational study. Lancet. 2007 Mar 17;369(9565):920-6. [PMID 17368153]

  • outcome measures @ 30 days (good outcomes)
    -> 2.2% no CPR
    -> 3.1% standard CPR
    -> 6.2% external cardiac massage only
    -> external cardiac massage may be better than standard CPR

Automated external defibrillators (AED)

Bardy et al. Home Use of Automated External Defibrillators for Sudden Cardiac Arrest. N Engl J Med 2008; 358:1793-1804

  • n = 7001 patients
  • mean age 62 years
    -> AED group produced 4 survivors (out of 3500 patients)
    -> need to arrest at home and be witnessed for an AED to be beneficial

Chan PS et al. Automated external defibrillators and survival after in-hospital cardiac arrest. JAMA. 2010 Nov 17;304(19):2129-36. [PMID 21078809]

  • AED’s improve survival in out-of-hospital cardiac arrest.
  • data on effectiveness in hospitalized patients are limited.
  • cohort study
  • n = 11,695
  • 204 US hospitals following the introduction of AEDs to general hospital wards
  • 82.2% had a nonshockable rhythm (asystole and PEA)
  • 17.8% had a shockable rhythm (VF and pulseless VT)
  • AED’s used in 38.6% of time
  • 18% survival to hospital discharge
    -> overall AED use associated with a lower rate of survival
    -> AED use in nonshockable cardiac arrest associated with a significantly lower survival
    -> AED use in shockable cardiac arrest not associated with survival!

CCC 700 6

Critical Care


Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of three amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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