Extracorporeal cardiopulmonary resuscitation versus standard treatment for refractory out-of-hospital cardiac arrest: a Bayesian meta-analysis.

BACKGROUND: The outcomes of several randomized trials on extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out-of-hospital cardiac arrest were examined using frequentist methods, resulting in a dichotomous interpretation of results based on p-values rather than in the probability of clinically relevant treatment effects. To determine such a probability of a clinically relevant ECPR-based treatment effect on neurological outcomes, the authors of these trials performed a Bayesian meta-analysis of the totality of randomized ECPR evidence. METHODS: A systematic search was applied to three electronic databases. Randomized trials that compared ECPR-based treatment with conventional CPR for refractory out-of-hospital cardiac arrest were included. The study was preregistered in INPLASY (INPLASY2023120060). The primary Bayesian hierarchical meta-analysis estimated the difference in 6-month neurologically favorable survival in patients with all rhythms, and a secondary analysis assessed this difference in patients with shockable rhythms (Bayesian hierarchical random-effects model). Primary Bayesian analyses were performed under vague priors. Outcomes were formulated as estimated median relative risks, mean absolute risk differences, and numbers needed to treat with corresponding 95% credible intervals (CrIs). The posterior probabilities of various clinically relevant absolute risk difference thresholds were estimated. RESULTS: Three randomized trials were included in the analysis (ECPR, n = 209 patients; conventional CPR, n = 211 patients). The estimated median relative risk of ECPR for 6-month neurologically favorable survival was 1.47 (95%CrI 0.73-3.32) with a mean absolute risk difference of 8.7% (- 5.0; 42.7%) in patients with all rhythms, and the median relative risk was 1.54 (95%CrI 0.79-3.71) with a mean absolute risk difference of 10.8% (95%CrI - 4.2; 73.9%) in patients with shockable rhythms. The posterior probabilities of an absolute risk difference > 0% and > 5% were 91.0% and 71.1% in patients with all rhythms and 92.4% and 75.8% in patients with shockable rhythms, respectively. CONCLUSION: The current Bayesian meta-analysis found a 71.1% and 75.8% posterior probability of a clinically relevant ECPR-based treatment effect on 6-month neurologically favorable survival in patients with all rhythms and shockable rhythms. These results must be interpreted within the context of the reported credible intervals and varying designs of the randomized trials. REGISTRATION: INPLASY (INPLASY2023120060, December 14th, 2023, https://doi.org/10.37766/inplasy2023.12.0060 ).

Favorable resuscitation characteristics in patients undergoing extracorporeal cardiopulmonary resuscitation: A secondary analysis of the INCEPTION-trial.

Introduction: Extracorporeal cardiopulmonary resuscitation (ECPR) is increasingly used as a supportive treatment for refractory out-of-hospital cardiac arrest (OHCA). Still, there is a paucity of data evaluating favorable and unfavorable prognostic characteristics in patients considered for ECPR. Methods: We performed a previously unplanned post-hoc analysis of the multicenter randomized controlled INCEPTION-trial. The study group consisted of patients receiving ECPR, irrespective of initial group randomization. The patients were divided into favorable survivors (cerebral performance category [CPC] 1-2) and unfavorable or non-survivors (CPC 3-5). Results: In the initial INCEPTION-trial, 134 patients were randomized. ECPR treatment was started in 46 (66%) of 70 patients in the ECPR treatment arm and 3 (4%) of 74 patients in the conventional treatment arm. No statistically significant differences in baseline characteristics, medical history, or causes of arrest were observed between survivors (n = 5) and non-survivors (n = 44). More patients in the surviving group had a shockable rhythm at the time of cannulation (60% vs. 14%, p = 0.037), underwent more defibrillation attempts (13 vs. 6, p = 0.002), and received higher dosages of amiodarone (450 mg vs 375 mg, p = 0.047) despite similar durations of resuscitation maneuvers. Furthermore, non-survivors more frequently had post-ECPR implantation adverse events. Conclusion: The persistence of ventricular arrhythmia is a favorable prognostic factor in patients with refractory OHCA undergoing an ECPR-based treatment. Future studies are warranted to confirm this finding and to establish additional prognostic factors.Clinical trial Registration:clinicaltrials.gov registration number NCT03101787.

Extracorporeal life support in cardiac arrest: a post hoc Bayesian re-analysis of the INCEPTION trial.

AIMS: Previously, we performed the multicentre INCEPTION trial, randomizing patients with refractory out-of-hospital cardiac arrest (OHCA) to extracorporeal cardiopulmonary resuscitation (ECPR) or conventional cardiopulmonary resuscitation (CCPR). Frequentist analysis showed no statistically significant treatment effect for the primary outcome; 30-day survival with a favourable neurologic outcome (cerebral performance category score of 1-2). To facilitate a probabilistic interpretation of the results, we present a Bayesian re-analysis of the INCEPTION trial. METHODS AND RESULTS: We analysed survival with a favourable neurologic outcome at 30 days and 6 months under a minimally informative prior in the intention-to-treat population. Effect sizes are presented as absolute risk differences (ARDs) and relative risks (RRs), with 95% credible intervals (CrIs). We estimated posterior probabilities at various thresholds, including the minimal clinically important difference (MCID) (5% ARD), based on expert consensus, and performed sensitivity analyses under sceptical and literature-based priors. The mean ARD for 30-day survival with a favourable neurologic outcome was 3.6% (95% CrI -9.5-16.7%), favouring ECPR, with a median RR of 1.22 (95% CrI 0.59-2.51). The posterior probability of an MCID was 42% at 30 days and 42% at 6 months, in favour of ECPR. CONCLUSION: Bayesian re-analysis of the INCEPTION trial estimated a 42% probability of an MCID between ECPR and CCPR in refractory OHCA in terms of 30-day survival with a favourable neurologic outcome. TRIAL REGISTRATION: Clinicaltrials.gov (NCT03101787, registered 5 April 2017).

Early extracorporeal CPR for refractory out-of-hospital cardiac arrest - A pre-planned per-protocol analysis of the INCEPTION-trial.

BACKGROUND: Evidence for extracorporeal cardiopulmonary resuscitation (CPR) in refractory out-of-hospital cardiac arrest (OHCA) remains inconclusive. Recently, the INCEPTION-trial, comparing extracorporeal with conventional CPR, found no statistically significant difference in neurologically favorable survival. Since protocol deviations were anticipated, a pre-specified per-protocol analysis was foreseen. METHODS: The per-protocol analysis of the INCEPTION trial excluded patients not meeting inclusion or exclusion criteria, amongst which time-to-cannulation of >60 minutes, and achieving a return of spontaneous circulation before hospital arrival. Crossovers were excluded as well. The primary outcome (30-day survival in a neurologically favorable condition; cerebral performance category [CPC] 1-2) was primarily analyzed under a frequentist statistical framework. In addition, Bayesian analysis under a minimally informative prior was performed. RESULTS: Eighty-one patients were included in the per-protocol analysis (extracorporeal CPR n = 33, conventional CPR n = 48). Thirty-day survival with CPC1-2 was 15% in the extracorporeal CPR group versus 9% in the conventional CPR group (adjusted OR 1.9; 95% CI 0.4-9.3; p-value 0.393). Bayesian analysis showed an 84% posterior probability of any ECPR benefit and a 61% posterior probability of a 5% absolute risk reduction for the primary outcome. CONCLUSION: A pre-planned, pre-specified per-protocol analysis of the INCEPTION-trial, found a higher survival with favorable neurological in patients undergoing ECPR versus CCPR for refractory shockable OHCA. This difference did not reach statistical significance, but results should be interpreted with care, in the light of the small remaining sample size.

Extracorporeal cardiopulmonary resuscitation for refractory OHCA: lessons from three randomized controlled trials-the trialists' view.

Extracorporeal cardiopulmonary resuscitation is a promising treatment for refractory out-of-hospital cardiac arrest. Three recent randomized trials (ARREST trial, Prague OHCA study, and INCEPTION trial) that addressed the clinical benefit of extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest yielded seemingly diverging results. The evidence for extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest, derived from three recent randomized controlled trials, is not contradictory but rather complementary. Excellent results can be achieved with a very high level of dedication, provided that strict selection criteria are applied. However, pragmatic implementation of extracorporeal cardiopulmonary resuscitation does not necessarily lead to improved outcome of refractory out-of-hospital cardiac arrest. Centres that are performing extracorporeal cardiopulmonary resuscitation for out-of-hospital cardiac arrest or aspire to do so should critically evaluate whether they are able to meet the pre-requisites that are needed to conduct an effective extracorporeal cardiopulmonary resuscitation programme.

Nitric Oxide Ventilation Improves Recirculation and Right Ventricular Function During Veno-Venous Extracorporeal Membrane Oxygenation in a COVID-19 Patient.

Patients with coronavirus disease 2019 (COVID-19) are prone to pulmonary artery hypertension (PAH) and right ventricular pressure overload due to severe bilateral infiltrates, high ventilation pressures, persistent hypoxemia, pulmonary fibrosis, and/or pulmonary embolism. In patients on extracorporeal membrane oxygenation (ECMO), this potentially leads to increased recirculation. In the current report, the authors present a case in which continuous inhaled nitric oxide (iNO)-enriched ventilation was effective in terms of PAH and recirculation reduction in a COVID-19 patient on veno-venous ECMO.

A randomized prospective study comparing the Cobra Perilaryngeal Airway and Laryngeal Mask Airway-Classic during controlled ventilation for gynecological laparoscopy.

BACKGROUND: An increasing number of noninvasive, supraglottic airway devices are currently available. In this randomized single-blind study, we compared the Cobra Perilaryngeal Airway (CobraPLA) to the [Laryngeal Mask Airway (LMA)-Classic] during gynecological laparoscopy. METHODS: Forty patients received either an LMA-Classic or a CobraPLA. Insertion, ventilation and removal characteristics were noted, as well as any throat morbidity. RESULTS: Devices were similar for insertion characteristics, adverse events, and throat morbidity. Before pneumoperitoneum, peak airway pressures were 20.3 +/- 4.9 cm H2O in the LMA-Classic group versus 25.5 +/- 7.9 cm H2O in the CobraPLA group, P = 0.01. This difference was maintained during pneumoperitoneum; LMA-Classic (22.8 +/- 6.1 cm H2O) and CobraPLA (28.1 +/- 8.5 cm H2O), P = 0.04. Macroscopic blood occurred only on the CobraPLA, seen on 40% of the devices after removal, P = 0.001. CONCLUSION: During gynecological laparoscopy, the CobraPLA provides similar insertion characteristics, but higher airway sealing pressures than the LMA-Classic. The usefulness of this finding requires further investigation.

Pain in neurosurgically treated patients: a prospective observational study.

OBJECT: This is the first observational study to compare perioperative pain character and intensity in patients undergoing different types of elective neurosurgical procedures. METHODS: A structured questionnaire was used to inquire about pain intensity, character, and management during the perioperative course, and the anticipated visual analogue scale (VAS) score in 649 patients during a 1-year period. The anticipated maximal postoperative VAS score was lower than the actual postoperative maximal VAS score and was independent of operation type and preoperative VAS score. Patients undergoing craniotomy experienced less pain than those undergoing spinal surgery. A majority of patients did not receive analgesic medication after surgery. Patients undergoing spinal surgery experienced higher preoperative VAS scores than those undergoing other neurosurgical treatments, with a shift from preoperative referred pain to postoperative local pain. After lumbar flavectomy, referred pain was greater than local pain. Patients with preoperative pain suffered significantly more postoperative pain than those without preoperative pain. In patients with postoperative surgery-related complications, VAS scores were higher than in those without complications. CONCLUSIONS: Neurosurgical procedures cause more pain than anticipated. Anticipated pain intensity is independent of the operation type and preoperative pain intensity. Postcraniotomy on-demand analgesic medication is appropriate, if the nurses on the ward react quickly. Otherwise, patient-controlled analgesia might be an option. Other neurosurgical procedures require scheduled analgesic therapies. Spinal surgery requires intensive preoperative pain treatment; a shift in pain character from preoperative referred pain to postoperative local pain is expected. Patients with referred pain after lumbar flavectomy are prone to the most intense pain. Patients with preoperative pain experience more postoperative pain than those without preoperative pain and require more intensive pain management. Increased postoperative VAS scores are associated with surgery-related complications.

Remifentanil as a single drug for extracorporeal shock wave lithotripsy: a comparison of infusion doses in terms of analgesic potency and side effects.

UNLABELLED: This randomized, double-blind study was designed to evaluate analgesic effectiveness and side effects of two remifentanil infusion rates in patients undergoing extracorporeal shock wave lithotripsy (ESWL) for renal stones. We included 200 patients who were administered remifentanil either 0.05 microg x kg(-1) x min(-1) (n = 100) or 0.1 microg x kg(-1) x min(-1) (n = 100) plus demand bolus of 10 microg of remifentanil via a patient-controlled analgesia (PCA) device. No other sedating drugs were given. The frequencies of PCA demands and deliveries were recorded. Arterial blood pressure, oxygen saturation, and respiratory rate were recorded throughout the procedure; postoperative nausea and vomiting (PONV), dizziness, itching, agitation, and respiratory depression were measured posttreatment. Visual analog scale (VAS) scores were taken preoperatively, directly postoperatively, and 30 min after finishing the procedure. There were no statistically significant differences in the frequency of PCA demands and delivered boluses or among perioperative VAS scores. The extent of PONV and frequency of dizziness and itching immediately after and dizziness 30 min after the end of treatment were significantly reduced in the smaller dose group. We conclude that a remifentanil regimen of 0.05 microg x kg(-1) x min(-1) plus 10 microg demands is superior to 0.1 microg x kg(-1) x min(-1) plus demands, as there was no difference in the VAS scores recorded between groups and it has a less frequent incidence of side effects in patients receiving ESWL. IMPLICATIONS: Remifentanil is an appropriate analgesic choice for patients undergoing extracorporeal shock wave lithotripsy (ESWL) therapy, as it has both fast onset and offset times. We studied remifentanil as a sole drug for ESWL and have shown that an infusion rate of 0.05 microg x kg-1 x min-1 plus patient-controlled analgesia demands of 10 microg provides adequate analgesia and has significantly less side effects than a dose of 0.1 microg x kg-1 x min-1 plus 10 microg demands.