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

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Using a Structured Assessment Tool to Evaluate Nontechnical Skills of Nurse Anesthetists.

Nontechnical skills are critical for good anesthetic practice but are seldom addressed explicitly in clinical training. The purposes of this study were (1) to evaluate the reliability and validity of the observation-based assessment tool Nurse Anaesthetists' Non-Technical Skills system (N-ANTS) and (2) to evaluate the effect of training nurse anesthetist supervisors in the use of N-ANTS. This system comprises a global rating score, 4 categories, and 15 elements to rate nurse anesthetists' nontechnical skills. A 1-day workshop was conducted for 22 nurse anesthetist supervisors to rate nurse anesthetists' nontechnical skills in 9 scripted video scenarios. Data were gathered from 2 rating sessions separated by a 2-hour training session. The interrater reliability was high before and after the training. It remained stable for the global rating score in N-ANTS and its category ratings, but improved at the elements level. When the raters' ratings were compared with ratings by an expert reference group, there was no statistically significant effect on training. We conclude that Danish nurse anesthetist supervisors without further rater training besides their work experience can use N-ANTS to assess nontechnical skills of nurse anesthetists.

Thromboembolic risk in 16 274 atrial fibrillation patients undergoing direct current cardioversion with and without oral anticoagulant therapy.

AIMS: To study the risk of thromboembolism in a nationwide cohort of atrial fibrillation patients undergoing direct current (DC) cardioversion with or without oral anticoagulant coverage. METHODS AND RESULTS: A retrospective study of 16 274 patients in Denmark discharged from hospital after a first-time DC cardioversion for atrial fibrillation between 2000 and 2008. Use of oral anticoagulant therapy within 90 days prior and 360 days after DC cardioversion was obtained from the Danish Register of Medicinal Product Statistics. The risk of thromboembolism was estimated by calculating incidence rates and by multivariable adjusted Cox proportional-hazard models. During the initial 30 days following discharge, the thromboembolic incidence rate was 10.33 per 100 patient-years for the no prior oral anticoagulant therapy group [n = 5084 (31.2%)], as compared with 4.00 per 100 patient-years for the prior oral anticoagulant therapy group [n = 11 190 (68.8%)], [hazard ratio associated with no prior oral anticoagulant therapy was 2.25; 95% confidence interval (CI), 1.43-3.53]. Thromboembolic risk stratification by the CHADS2 and CHA2DS2-VASc scores did not change the results. Hazard ratio with no oral anticoagulant therapy was 2.21; 95% CI, 0.79-6.77 and 2.40; 95% CI, 1.46-3.95 with CHA2DS2-VASc score 0-1 and CHA2DS2-VASc score 2 or more, respectively. CONCLUSION: Direct current cardioversion for atrial fibrillation without oral anticoagulation is associated with a high risk of thromboembolism. Notably, the risk is high in the initial period after cardioversion, indicating a hazardous association between DC cardioversion without anticoagulation and thromboembolism.

Effect of vasopressin and methylprednisolone vs. placebo on long-term outcomes in patients with in-hospital cardiac arrest a randomized clinical trial.

OBJECTIVE: The primary results from the Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial have previously been reported. The objective of the current manuscript is to report long-term outcomes. METHODS: The VAM-IHCA trial was a multicenter, randomized, double-blind, placebo-controlled trial conducted at ten hospitals in Denmark. Adult patients (age ≥ 18 years) were eligible for the trial if they had an in-hospital cardiac arrest and received at least one dose of epinephrine during resuscitation. The trial drugs consisted of 40 mg methylprednisolone (Solu-Medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of epinephrine. This manuscript report outcomes at 6 months and 1 year including survival, survival with favorable neurological outcome, and health-related quality of life. RESULTS: 501 patients were included in the analysis. At 1 year, 15 patients (6.3%) in the intervention group and 22 patients (8.3%) in the placebo group were alive corresponding to a risk ratio of 0.76 (95% CI, 0.41-1.41). A favorable neurologic outcome at 1 year, based on the Cerebral Performance Category score, was observed in 14 patients (5.9%) in the intervention group and 20 patients (7.6%) in the placebo group (risk ratio, 0.78 [95% CI, 0.41-1.49]. No differences existed between groups for favorable neurological outcome and health-related quality of life at either 6 months or 1 year. CONCLUSIONS: Administration of vasopressin and methylprednisolone, compared with placebo, in patients with in-hospital cardiac arrest did not improve long-term outcomes in this trial.

Vasopressin and methylprednisolone for in-hospital cardiac arrest - Protocol for a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To describe the clinical trial "Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest" (VAM-IHCA). METHODS: The VAM-IHCA trial is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. The study drugs consist of 40 mg methylprednisolone and 20 IU of vasopressin given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).The primary outcome is return of spontaneous circulation and key secondary outcomes include survival and survival with a favorable neurological outcome at 30 days. 492 patients will be enrolled. The trial was registered at the EU Clinical Trials Register (EudraCT Number: 2017-004773-13) on Jan. 25, 2018 and ClinicalTrials.gov (Identifier: NCT03640949) on Aug. 21, 2018. RESULTS: The trial started in October 2018 and the last patient is anticipated to be included in January 2021. The primary results will be reported after 3-months follow-up and are, therefore, anticipated in mid-2021. CONCLUSION: The current article describes the design of the VAM-IHCA trial. The results from this trial will help clarify whether the combination of vasopressin and methylprednisolone when administered during in-hospital cardiac arrest improves outcomes.