Objectives
To review and update the evidence on predictors of poor outcome (death, persistent vegetative state or severe neurological disability) in adult comatose survivors of cardiac arrest, either treated or not treated with controlled temperature, to identify knowledge gaps and to suggest a reliable prognostication strategy.

/pdf/prognostication-in-comatose-survivors-of-cardiac-arrest-an-1g3vu344lg.pdf

Prognostication in comatose survivors of cardiac arrest: an advisory statement from the European Resuscitation Council and the European Society of Intensive Care Medicine.

http://www.afarcome.altervista.org/hypothermia.pdf

Predictors of poor neurological outcome in adult comatose survivors of cardiac arrest: A systematic review and meta-analysis. Part 2: Patients treated with therapeutic hypothermia

Background
Therapeutic hypothermia is commonly used in comatose survivors’ post-cardiopulmonary resuscitation (CPR). It is unknown whether outcome predictors perform accurately after hypothermia treatment.

/pdf/sedation-confounds-outcome-prediction-in-cardiac-arrest-5d66v124py.pdf

Sedation Confounds Outcome Prediction in Cardiac Arrest Survivors Treated with Hypothermia

To assess the ability of clinical examination, blood biomarkers, electrophysiology, or neuroimaging assessed within 7 days from return of spontaneous circulation (ROSC) to predict poor neurological outcome, defined as death, vegetative state, or severe disability (CPC 3–5) at hospital discharge/1 month or later, in comatose adult survivors from cardiac arrest (CA). PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews (January 2013–April 2020) were searched. Sensitivity and false-positive rate (FPR) for each predictor were calculated. Due to heterogeneities in recording times, predictor thresholds, and definition of some predictors, meta-analysis was not performed. Ninety-four studies (30,200 patients) were included. Bilaterally absent pupillary or corneal reflexes after day 4 from ROSC, high blood values of neuron-specific enolase from 24 h after ROSC, absent N20 waves of short-latency somatosensory-evoked potentials (SSEPs) or unequivocal seizures on electroencephalogram (EEG) from the day of ROSC, EEG background suppression or burst-suppression from 24 h after ROSC, diffuse cerebral oedema on brain CT from 2 h after ROSC, or reduced diffusion on brain MRI at 2–5 days after ROSC had 0% FPR for poor outcome in most studies. Risk of bias assessed using the QUIPS tool was high for all predictors. In comatose resuscitated patients, clinical, biochemical, neurophysiological, and radiological tests have a potential to predict poor neurological outcome with no false-positive predictions within the first week after CA. Guidelines should consider the methodological concerns and limited sensitivity for individual modalities. (PROSPERO CRD42019141169)

/pdf/prediction-of-poor-neurological-outcome-in-comatose-141kjucqma.pdf

Prediction of poor neurological outcome in comatose survivors of cardiac arrest: a systematic review

Perioperative complications of hypothermia.

Therapeutic hypothermia may alter the required dosage of analgesics and sedatives, but no data are available on the effects of mild hypothermia on plasma fentanyl concentration during continuous, long-term administration. We therefore assessed in a porcine model the effect of prolonged hypothermia on plasma fentanyl concentration during 33 h of continuous fentanyl administration. Seven female piglets (weight: 11.8 +/- 1.1 kg) were anesthetized by IV fentanyl (15 microg . kg(-1) . h(-1)) and midazolam (1.0 mg . kg(-1) . h(-1)). After preparation and stabilization (12 h), the animals were cooled to a core temperature of 31.6 degrees +/- 0.2 degrees C for 6 h and were then rewarmed and kept normothermic at 37.7 degrees +/- 0.3 degrees C for 6 more hours. Plasma fentanyl concentrations were measured by radioimmunoassay, cardiac index by thermodilution, and blood flows of the kidney, spleen, pancreas, stomach, gut, and hepatic artery by a colored microspheres technique. Furthermore, in an additional 4 pigs, temperature dependency of hepatic microsomal cytochrome P450 3A4 (CYP3A4) was determined in vitro by ethylmorphine N-demethylation. Plasma fentanyl concentration increased by 25% +/- 11% (P < 0.05) during hypothermia and remained increased for at least 6 h after rewarming. Hypothermia reduced the cardiac index (41% +/- 15%, P < 0.05), as well as all organ blood flows except the hepatic artery. A strong temperature dependency of CYP3A4 was found (P < 0.01). Mild hypothermia induced a distribution and/or elimination-dependent increase in plasma fentanyl concentration which remained increased for several hours after rewarming. Consequently, a prolonged increase of the plasma fentanyl concentration should be anticipated for appropriate control of the analgesia/sedatives during and early after therapeutic hypothermia.

The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs.

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The effect of mild hypothermia on plasma fentanyl concentration and biotransformation in juvenile pigs.