Top 10 Cardiac Arrest Randomized Trials of 2021

2500 articles were published in 2021 in the fields of cardiac arrest, CPR and resuscitation.

I systematically searched and selected 10 RCTs that I considered the most relevant landmark trials of 2021 in the fields of Cardiac Arrest, CPR and Resuscitation Science.

Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest

By Dankiewicz J et al. N Engl J Med.

  • Intervention: Hypothermia at 33°C
  • Control: Normothermia with early treatment of fever
  • Setting: Resuscitated OHCA
  • Sample: 1850 patients
  • Primary outcome: Death from any cause at 6 months
    • 50% vs 48% (RR 1.04; 95% CI 0.94–1.14; P=0.37)
  • Main findings: In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia

Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation

By Desch S et al. N Engl J Med.

  • Intervention: Immediate coronary angiography
  • Control: Delayed coronary angiography
  • Setting: Resuscitated OHCA
  • Sample: 554 patients
  • Primary outcome: Death from any cause at 30 days
    • 54.0% vs. 46.0% (HR 1.28; 95% CI 1.00 to 1.63; P=0.06)
  • Main findings: Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause.

Effect of Moderate vs Mild Therapeutic Hypothermia on Mortality and Neurologic Outcomes in Comatose Survivors of Out-of-Hospital Cardiac Arrest: The CAPITAL CHILL Randomized Clinical Trial

By Le May M et al. JAMA.

  • Intervention: Hypothermia at 31°C
  • Control: Mild hypothermia at 34°C
  • Setting: Resuscitated OHCA
  • Sample: 367 patients
  • Primary outcome: All-cause mortality or poor neurologic outcome at 180 days
    • 48.4% vs 45.4% (RR 1.07; 95% CI 0.86-1.33; P = 0.56)
  • Main findings: In comatose survivors of out-of-hospital cardiac arrest, a target temperature of 31 °C did not significantly reduce the rate of death or poor neurologic outcome at 180 days compared with a target temperature of 34 °C.

Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial

By Vallentin MF et al. JAMA.

  • Intervention: IV or IO Calcium
  • Control: Saline
  • Setting: OHCA
  • Sample: 391 patients
  • Primary outcome: ROSC
    • 19% vs. 27% (risk ratio, 0.72 [95% CI, 0.49 to 1.03] P=0.09)
  • Main findings: Among adults with out-of-hospital cardiac arrest, treatment with intravenous or intraosseous calcium compared with saline did not significantly improve sustained return of spontaneous circulation.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial

By Andersen LW et al. JAMA.

  • Intervention: Vasopressin and Methylprednisolone
  • Control: Placebo
  • Setting: IHCA
  • Sample: 501 patients
  • Primary outcome: ROSC
    • 42% vs 33% (RR 1.30 [95% CI, 1.03-1.63]; P=0.03)
  • Main findings: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation.

Hyperinvasive Approach in Refractory Out-of-Hospital Cardiac Arrest. Prague OHCA study. A Randomized Clinical Trial

By Belohlavek J et al. Abstract at ACC 2021.

  • Intervention: Hyperinvasive (early transport under mechanical CPR + E-CPR)
  • Control: Standard ALS
  • Setting: Refractory OHCA
  • Sample: 364 patients
  • Primary outcome: 6 months survival with good neurological outcome
    • 31.5% vs 22.0% (P=0.09)
  • Main findings: In patients with refractory OHCA, a hyperinvasive approach did not improved survival with good neurological outcome at 6 months than a standard approach.

Effect of Machine Learning on Dispatcher Recognition of Out-of-Hospital Cardiac Arrest During Calls to Emergency Medical Services: A Randomized Clinical Trial

By Blomberg SN et al. JAMA Netw Open.

  • Intervention: Machine learning recognition of OHCA
  • Control: Standard dispatcher protocols
  • Setting: OHCA
  • Sample: 654 patients
  • Primary outcome: Rate of dispatcher OHCA recognition
    • 93.1% vs 90.5% (P=0.15)
  • Main findings: This randomized clinical trial did not find any significant improvement in dispatchers’ ability to recognize cardiac arrest when supported by machine learning even though artificial intelligence did surpass human recognition.

Treatment Effects of Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response After Out-of-Hospital Cardiac Arrest (The IMICA Trial): A Double-Blinded, Placebo-Controlled, Single-Center, Randomized, Clinical Trial.

By Meyer MAS et al. Circulation.

  • Intervention: Tocilizumab (IL-6 receptor antagonist)
  • Control: Placebo
  • Setting: Resuscitated OHCA
  • Sample: 80 patients
  • Primary outcome: Reduction in CRP from baseline until 72h
    • 96% reduction (97-94%; P<0.001)
  • Main findings: Treatment with tocilizumab resulted in a significant reduction in systemic inflammation and myocardial injury in comatose patients resuscitated from out-of-hospital cardiac arrest.

Impact of rewarming rate on interleukin-6 levels in patients with shockable cardiac arrest receiving targeted temperature management at 33 °C: the ISOCRATE pilot randomized controlled trial

By Lascarrou JB et al. Crit Care.

  • Intervention: Rewarming at 0.50°C/h after TTM at 33°C
  • Control: Rewarming at 0.25°C/h
  • Setting: Resuscitated OHCA
  • Sample: 50 patients
  • Primary outcome: Serum IL-6 level 24-48h
    • 12,389 [7256-37,200] vs. 8859 [6825-18,088] pg/mL h (P=0.55)
  • Main findings: Rewarming at a rate of 0.25 °C/h, compared to 0.50 °C, did not result in lower serum IL6 levels after achievement of hypothermia at 33 °C in patients who remained comatose after shockable cardiac arrest

Ubiquinol (reduced coenzyme Q10) as a metabolic resuscitator in post-cardiac arrest: A randomized, double-blind, placebo-controlled trial

By Holmberg MJ et al. Resuscitation.

  • Intervention: Ubiquinol (300 mg) every 12h for up to 7 days
  • Control: Placebo
  • Setting: Resuscitated OHCA/IHCA
  • Sample: 43 patients
  • Primary outcome: Total coenzyme Q10 plasma levels at 24 h after enrollment:
    • 441 [IQR, 215-510] ηg/mL vs. 113 [IQR, 94-208] ηg/mL (P < 0.001)
  • Main findings: Administration of enteral ubiquinol increased plasma coenzyme Q10 levels in post-cardiac arrest patients as compared to placebo. There were no differences in neurological biomarkers and oxygen consumption between the two groups.
Tommaso Scquizzato
Tommaso Scquizzato

Tommaso Scquizzato is a researcher in the fields of cardiac arrest and resuscitation science at the Center for Intensive Care and Anesthesiology of San Raffaele Hospital in Milan, Italy. He is the Social Media Editor of Resuscitation, member of the Social Media Working Group of ILCOR, and member of the ERC BLS Science and Education Committee.

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