Dataset Information

Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest.

ABSTRACT:

Background

Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known.

Methods

In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular fibrillation/pulseless ventricular tachycardia out-of-hospital cardiac arrest who were randomly assigned by emergency medical services personnel to an antiarrhythmic drug versus placebo in the ALPS trial (Resuscitation Outcomes Consortium Amiodarone, Lidocaine or Placebo Study), when stratified by the intravenous versus intraosseous route of administration.

Results

Of 3019 randomly assigned patients with a known vascular access site, 2358 received ALPS drugs intravenously and 661 patients by the intraosseous route. Intraosseous and intravenous groups differed in sex, time-to-emergency medical services arrival, and some cardiopulmonary resuscitation characteristics, but were similar in others, including time-to-intravenous/intrasosseous drug receipt. Overall hospital discharge survival was 23%. In comparison with placebo, discharge survival was significantly higher in recipients of intravenous amiodarone (adjusted risk ratio, 1.26 [95% CI, 1.06-1.50]; adjusted absolute survival difference, 5.5% [95% CI, 1.5-9.5]) and intravenous lidocaine (adjusted risk ratio, 1.21 [95% CI, 1.02-1.45]; adjusted absolute survival difference, 4.7% [95% CI, 0.7-8.8]); but not in recipients of intraosseous amiodarone (adjusted risk ratio, 0.94 [95% CI, 0.66-1.32]) or intraosseous lidocaine (adjusted risk ratio, 1.03 [95% CI, 0.74-1.44]). Survival to hospital admission also increased significantly when drugs were given intravenously but not intraosseously, and favored improved neurological outcome at discharge. There were no outcome differences between intravenous and intraosseous placebo, indicating that the access route itself did not demarcate patients with poor prognosis. The study was underpowered to assess intravenous/intraosseous drug interactions, which were not statistically significant.

Conclusions

We found no significant effect modification by drug administration route for amiodarone or lidocaine in comparison with placebo during out-of-hospital cardiac arrest. However, point estimates for the effects of both drugs in comparison with placebo were significantly greater for the intravenous than for the intraosseous route across virtually all outcomes and beneficial only for the intravenous route. Given that the study was underpowered to statistically assess interactions, these findings signal the potential importance of the drug administration route during resuscitation that merits further investigation.

SUBMITTER: Daya MR

PROVIDER: S-EPMC7009320 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest.

Daya Mohamud R MR Leroux Brian G BG Dorian Paul P Rea Thomas D TD Newgard Craig D CD Morrison Laurie J LJ Lupton Joshua R JR Menegazzi James J JJ Ornato Joseph P JP Sopko George G Christenson Jim J Idris Ahamed A Mody Purav P Vilke Gary M GM Herdeman Caroline C Barbic David D Kudenchuk Peter J PJ

Circulation 20200116 3

<h4>Background</h4>Antiarrhythmic drugs have not proven to significantly improve overall survival after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/pulseless ventricular tachycardia. How this might be influenced by the route of drug administration is not known.<h4>Methods</h4>In this prespecified analysis of a randomized, placebo-controlled clinical trial, we compared the differences in survival to hospital discharge in adults with shock-refractory ventricular f ...[more]

PMID: 31941354

Similar Datasets

Project description:BACKGROUND:Out-of-hospital cardiac arrest (OHCA) commonly presents with nonshockable rhythms (asystole and pulseless electric activity). It is unknown whether antiarrhythmic drugs are safe and effective when nonshockable rhythms evolve to shockable rhythms (ventricular fibrillation/pulseless ventricular tachycardia [VF/VT]) during resuscitation. METHODS:Adults with nontraumatic OHCA, vascular access, and VF/VT anytime after ?1 shock(s) were prospectively randomized, double-blind, to receive amiodarone, lidocaine, or placebo by paramedics. Patients presenting with initial shock-refractory VF/VT were previously reported. The current study was a prespecified analysis in a separate cohort that initially presented with nonshockable OHCA and was randomized on subsequently developing shock-refractory VF/VT. The primary outcome was survival to hospital discharge. Secondary outcomes included discharge functional status and adverse drug-related effects. RESULTS:Of 37?889 patients with OHCA, 3026 with initial VF/VT and 1063 with initial nonshockable-turned-shockable rhythms were treatment-eligible, were randomized, and received their assigned drug. Baseline characteristics among patients with nonshockable-turned-shockable rhythms were balanced across treatment arms, except that recipients of a placebo included fewer men and were less likely to receive bystander cardiopulmonary resuscitation. Active-drug recipients in this cohort required fewer shocks, supplemental doses of their assigned drug, and ancillary antiarrhythmic drugs than recipients of a placebo (P<0.05). In all, 16 (4.1%) amiodarone, 11 (3.1%) lidocaine, and 6 (1.9%) placebo-treated patients survived to hospital discharge (P=0.24). No significant interaction between treatment assignment and discharge survival occurred with the initiating OHCA rhythm (asystole, pulseless electric activity, or VF/VT). Survival in each of these categories was consistently higher with active drugs, although the trends were not statistically significant. Adjusted absolute differences (95% confidence interval) in survival from nonshockable-turned-shockable arrhythmias with amiodarone versus placebo were 2.3% (-0.3, 4.8), P=0.08, and for lidocaine versus placebo 1.2% (-1.1, 3.6), P=0.30. More than 50% of these survivors were functionally independent or required minimal assistance. Drug-related adverse effects were infrequent. CONCLUSIONS:Outcome from nonshockable-turned-shockable OHCA is poor but not invariably fatal. Although not statistically significant, point estimates for survival were greater after amiodarone or lidocaine than placebo, without increased risk of adverse effects or disability and consistent with previously observed favorable trends from treatment of initial shock-refractory VF/VT with these drugs. Together the findings may signal a clinical benefit that invites further investigation. CLINICAL TRIAL REGISTRATION:URL: https://www.clinicaltrials.gov. Unique identifier: NCT01401647.

Project description:ObjectiveTo compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest.DesignCluster randomised controlled trial.SettingThe VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic.ParticipantsAdult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest.InterventionsBiweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access.Main outcome measuresThe primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge.ResultsAmong 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes.ConclusionsAmong adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes.Trial registrationNCT04135547ClinicalTrials.gov NCT04135547.

Project description:IntroductionThis study is aimed to investigate the association of intraosseous (IO) versus intravenous (IV) route during cardiopulmonary resuscitation (CPR) with outcomes after out-of-hospital cardiac arrest (OHCA).MethodsWe systematically searched PubMed, Embase, Cochrane Library and Web of Science from the database inception through April 2020. Our search strings included designed keywords for two concepts, i.e. vascular access and cardiac arrest. There were no limitations implemented in the search strategy. We selected studies comparing IO versus IV access in neurological or survival outcomes after OHCA. Favourable neurological outcome at hospital discharge was pre-specified as the primary outcome. We pooled the effect estimates in random-effects models and quantified the heterogeneity by the I2 statistics. Time to intervention, defined as time interval from call for emergency medical services to establishing vascular access or administering medications, was hypothesized to be a potential outcome moderator and examined in subgroup analysis with meta-regression.ResultsNine retrospective observational studies involving 111,746 adult OHCA patients were included. Most studies were rated as high quality according to Newcastle-Ottawa Scale. The pooled results demonstrated no significant association between types of vascular access and the primary outcome (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.27-1.33; I2, 95%). In subgroup analysis, time to intervention was noted to be positively associated with the pooled OR of achieving the primary outcome (OR: 3.95, 95% CI, 1.42-11.02, p: 0.02). That is, when the studies not accounting for the variable of "time to intervention" in the statistical analysis were pooled together, the meta-analytic results between IO access and favourable outcomes would be biased toward inverse association. No obvious publication bias was detected by the funnel plot.ConclusionsThe meta-analysis revealed no significant association between types of vascular access and neurological outcomes at hospital discharge among OHCA patients. Time to intervention was identified to be an important outcome moderator in this meta-analysis of observation studies. These results call for the need for future clinical trials to investigate the unbiased effect of IO use on OHCA CPR.

Project description:ImportanceIt is unclear whether administration of calcium has a beneficial effect in patients with cardiac arrest.ObjectiveTo determine whether administration of calcium during out-of-hospital cardiac arrest improves return of spontaneous circulation in adults.Design, setting, and participantsThis double-blind, placebo-controlled randomized clinical trial included 397 adult patients with out-of-hospital cardiac arrest and was conducted in the Central Denmark Region between January 20, 2020, and April 15, 2021. The last 90-day follow-up was on July 15, 2021.InterventionsThe intervention consisted of up to 2 intravenous or intraosseous doses with 5 mmol of calcium chloride (n = 197) or saline (n = 200). The first dose was administered immediately after the first dose of epinephrine.Main outcomes and measuresThe primary outcome was sustained return of spontaneous circulation. The secondary outcomes included survival and a favorable neurological outcome (modified Rankin Scale score of 0-3) at 30 days and 90 days.ResultsBased on a planned interim analysis of 383 patients, the steering committee stopped the trial early due to concerns about harm in the calcium group. Of 397 adult patients randomized, 391 were included in the analyses (193 in the calcium group and 198 in the saline group; mean age, 68 [SD, 14] years; 114 [29%] were female). There was no loss to follow-up. There were 37 patients (19%) in the calcium group who had sustained return of spontaneous circulation compared with 53 patients (27%) in the saline group (risk ratio, 0.72 [95% CI, 0.49 to 1.03]; risk difference, -7.6% [95% CI, -16% to 0.8%]; P = .09). At 30 days, 10 patients (5.2%) in the calcium group and 18 patients (9.1%) in the saline group were alive (risk ratio, 0.57 [95% CI, 0.27 to 1.18]; risk difference, -3.9% [95% CI, -9.4% to 1.3%]; P = .17). A favorable neurological outcome at 30 days was observed in 7 patients (3.6%) in the calcium group and in 15 patients (7.6%) in the saline group (risk ratio, 0.48 [95% CI, 0.20 to 1.12]; risk difference, -4.0% [95% CI, -8.9% to 0.7%]; P = .12). Among the patients with calcium values measured who had return of spontaneous circulation, 26 (74%) in the calcium group and 1 (2%) in the saline group had hypercalcemia.Conclusions and relevanceAmong 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. These results do not support the administration of calcium during out-of-hospital cardiac arrest in adults.Trial registrationClinicalTrials.gov Identifier: NCT04153435.

Dataset Information

Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest.

Background

Methods

Results

Conclusions

Publications

Survival After Intravenous Versus Intraosseous Amiodarone, Lidocaine, or Placebo in Out-of-Hospital Shock-Refractory Cardiac Arrest.

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