Effect of neuromonitor-guided titrated care on brain tissue hypoxia after opioid overdose cardiac arrest

Resuscitation. 2018 Aug;129:121-126. doi: 10.1016/j.resuscitation.2018.04.013. Epub 2018 Apr 18.


Introduction: Brain tissue hypoxia may contribute to preventable secondary brain injury after cardiac arrest. We developed a porcine model of opioid overdose cardiac arrest and post-arrest care including invasive, multimodal neurological monitoring of regional brain physiology. We hypothesized brain tissue hypoxia is common with usual post-arrest care and can be prevented by modifying mean arterial pressure (MAP) and arterial oxygen concentration (PaO2).

Methods: We induced opioid overdose and cardiac arrest in sixteen swine, attempted resuscitation after 9 min of apnea, and randomized resuscitated animals to three alternating 6-h blocks of standard or titrated care. We invasively monitored physiological parameters including brain tissue oxygen (PbtO2). During standard care blocks, we maintained MAP > 65 mmHg and oxygen saturation 94-98%. During titrated care, we targeted PbtO2 > 20 mmHg.

Results: Overall, 10 animals (63%) achieved ROSC after a median of 12.4 min (range 10.8-21.5 min). PbtO2 was higher during titrated care than standard care blocks (unadjusted β = 0.60, 95% confidence interval (CI) 0.42-0.78, P < 0.001). In an adjusted model controlling for MAP, vasopressors, sedation, and block sequence, PbtO2 remained higher during titrated care (adjusted β = 0.75, 95%CI 0.43-1.06, P < 0.001). At three predetermined thresholds, brain tissue hypoxia was significantly less common during titrated care blocks (44 vs 2% of the block duration spent below 20 mmHg, P < 0.001; 21 vs 0% below 15 mmHg, P < 0.001; and, 7 vs 0% below 10 mmHg, P = .01).

Conclusions: In this model of opioid overdose cardiac arrest, brain tissue hypoxia is common and treatable. Further work will elucidate best strategies and impact of titrated care on functional outcomes.

Keywords: Cardiac arrest; Critical care; Neuromonitoring; Precision medicine; Resuscitation.

Publication types

  • Clinical Trial, Veterinary
  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / toxicity*
  • Animals
  • Brain Ischemia / etiology*
  • Brain Ischemia / physiopathology
  • Brain Ischemia / therapy
  • Cardiopulmonary Resuscitation / methods*
  • Cerebrovascular Circulation / physiology*
  • Cross-Over Studies
  • Disease Models, Animal
  • Drug Overdose / complications*
  • Drug Overdose / physiopathology
  • Female
  • Heart Arrest / chemically induced*
  • Heart Arrest / physiopathology
  • Heart Arrest / therapy
  • Monitoring, Physiologic / methods*
  • Prospective Studies
  • Random Allocation
  • Swine


  • Analgesics, Opioid