Adrenaline and vasopressin for cardiac arrest.
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SUBMITTER: Finn J
PROVIDER: S-EPMC6492484 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe 'Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug Administration In Cardiac Arrest' (PARAMEDIC2) trial showed that adrenaline improves overall survival, but not neurological outcomes. We sought to determine the within-trial and lifetime health and social care costs and benefits associated with adrenaline, including secondary benefits from organ donation.MethodsWe estimated the costs, benefits (quality-adjusted life years (QALYs)) and incremental cost-effectiveness ratios (ICERs) associated with adrenaline during the 6-month trial follow-up. Model-based analyses explored how results altered when the time horizon was extended beyond 6 months and the scope extended to include recipients of donated organs.ResultsThe within-trial (6 months) and lifetime horizon economic evaluations focussed on the trial population produced ICERs of £1,693,003 (€1,946,953) and £81,070 (€93,231) per QALY gained in 2017 prices, respectively, reflecting significantly higher mean costs and only marginally higher mean QALYs in the adrenaline group. The probability that adrenaline is cost-effective was less than 1% across a range of cost-effectiveness thresholds. Combined direct economic effects over the lifetimes of survivors and indirect economic effects in organ recipients produced an ICER of £16,086 (€18,499) per QALY gained for adrenaline with the probability that adrenaline is cost-effective increasing to 90% at a £30,000 (€34,500) per QALY cost-effectiveness threshold.ConclusionsAdrenaline was not cost-effective when only directly related costs and consequences are considered. However, incorporating the indirect economic effects associated with transplanted organs substantially alters cost-effectiveness, suggesting decision-makers should consider the complexity of direct and indirect economic impacts of adrenaline.Trial registrationISRCTN73485024 . Registered on 13 March 2014.
| S-EPMC7520962 | biostudies-literature
Project description:BackgroundAdrenaline is routinely administered during cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study evaluates the effects of adrenaline use on survival and end-organ injury.MethodsA total of 58 mice, including cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (in CA only) for 4-minutes prior to intravenous adrenaline (+ADR;250 ul,32 ug/ml) or saline (-ADR;250 ul) and manual chest compressions (300 BPM) for 4-minutes. Mice with return of spontaneous circulation (ROSC) were assessed at 24- or 72-h timepoints.ResultsAmong animals that underwent CA, rates of ROSC (n = 21 (95 %) vs n = 14 (82 %), P = 0.18) and survival to the planned endpoint (n = 11 (50 %) vs n = 12 (71 %), P = 0.19) were similar when comparing those treated with (CA+ADR) and without (CA-ADR) adrenaline. However, in CA animals that initially achieved ROSC, subsequent mortality was approximately 3-fold greater with adrenaline treatment (48 % vs 14 %, P = 0.042). Among SHAM animals, adrenaline use had no impact on survival rates or other endpoints. Greater myocardial injury occurred in CA+ADR vs CA-ADR, with increased Hs-Troponin levels measured at 24- (26.0 ± 0.9 vs 9.4 ± 5.3 ng/mL, P = 0.015) and 72-h (20.9 ± 8.3 vs 5.0 ± 2.4 ng/mL, P = 0.012), associated with increased expression of pro-inflammatory and fibrotic genes within cardiac and renal tissue.ConclusionAdrenaline did not improve ROSC or overall survival but following successful ROSC, its use resulted in 3-fold greater mortality rates. Adrenaline was also associated with increased myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further preclinical evaluation of alternate pharmacologic adjuncts for cardiopulmonary resuscitation that improve survival and limit end-organ injury.
| S-EPMC9436797 | biostudies-literature
Project description:Background The use of adrenaline in out-of-hospital cardiac arrest (OHCA) patients is still controversial. This study aimed to determine the effects of early pre-hospital adrenaline administration in OHCA patients. Methods and Results PubMed, EMBASE, Google Scholar, and the Cochrane Library database were searched from study inception to February 2019 to identify studies that reported OHCA patients who received adrenaline. The primary outcome was survival to discharge, and the secondary outcomes were return of spontaneous circulation, favorable neurological outcome, and survival to hospital admission. A total of 574 392 patients were included from 24 studies. The use of early pre-hospital adrenaline administration in OHCA patients was associated with a significant increase in survival to discharge (risk ratio [RR], 1.62; 95% CI, 1.45-1.83; P<0.001) and return of spontaneous circulation (RR, 1.50; 95% CI, 1.36-1.67; P<0.001), as well as a favorable neurological outcome (RR, 2.09; 95% CI, 1.73-2.52; P<0.001). Patients with shockable rhythm cardiac arrest had a significantly higher rate of survival to discharge (RR, 5.86; 95% CI, 4.25-8.07; P<0.001) and more favorable neurological outcomes (RR, 5.10; 95% CI, 2.90-8.97; P<0.001) than non-shockable rhythm cardiac arrest patients. Conclusions Early pre-hospital administration of adrenaline to OHCA patients might increase the survival to discharge, return of spontaneous circulation, and favorable neurological outcomes. Registration URL: https://www.crd.york.ac.uk/PROSPERO; Unique identifier: CRD42019130542.
| S-EPMC7429014 | biostudies-literature
Project description:ObjectiveTo demonstrate the therapeutic effect of vasopressin as an alternative treatment for cardiac arrest.DesignSystematic review and meta-analysis.MethodsPubMed, EMBASE, the Cochrane Library and Web of Science were searched for randomised controlled trials. The intervention included administration of vasopressin alone or vasopressin combined with epinephrine or vasopressin, steroids and epinephrine (VSE) versus epinephrine combined with placebo as control group. The primary outcome was the return of spontaneous circulation (ROSC). The secondary outcomes included mid-term survival and mid-term good neurological outcome. We conducted subgroup analyses of the primary outcome based on different settings, different study drug strategies and different types of initial rhythm.ResultsTwelve studies (n=6718) were included, of which eight trials (n=5638) reported the data on patients with out-of-hospital cardiac arrest and four trials (n=1080) on patients with in-hospital cardiac arrest (IHCA). There were no significant differences between intravenous vasopressin and placebo in the outcomes of ROSC (relative risk (RR): 1.11; 95% CI: 0.99 to 1.26), mid-term survival (RR: 1.23; 95% CI: 0.90 to 1.66) and mid-term good neurological outcome (RR: 1.20; 95% CI: 0.77 to 1.87). However, in the subgroup analysis, intravenous vasopressin as part of VSE can significantly improve the rate of ROSC (RR: 1.32; 95% CI: 1.18 to 1.47) but not the rate of mid-term survival (RR: 2.15; 95% CI: 0.75 to 6.16) and mid-term good neurological outcome (RR: 1.80; 95% CI: 0.81 to 4.01) for patients with IHCA.ConclusionsOur study failed to demonstrate increased benefit from vasopressin with or without epinephrine compared with the standard of care. However, vasopressin as a part of VSE is associated with the improvement of ROSC in patients with IHCA, and the benefit on mid-term survival or mid-term good neurological outcome is uncertain. Larger trials should be conducted in the future to address the effect of vasopressin only, vasopressin plus epinephrine or VSE on cardiac arrest.Prospero registration numberCRD42021293347.
| S-EPMC10111914 | biostudies-literature
Project description:Background and aimExpert guidelines for treatment of cardiac arrest recommend administration of adrenaline (epinephrine) every three to five minutes. However, the effects of different dosing periods of epinephrine remain unclear. We sought to evaluate the association between epinephrine average dosing period and survival to hospital discharge in adults with an in-hospital cardiac arrest (IHCA).MethodsWe performed a retrospective review of prospectively collected data on 20,909 IHCA events from 505 hospitals participating in the Get With The Guidelines-Resuscitation (GWTG-R) quality improvement registry. Epinephrine average dosing period was defined as the time between the first epinephrine dose and the resuscitation endpoint, divided by the total number of epinephrine doses received subsequent to the first epinephrine dose. Associations with survival to hospital discharge were assessed by using generalized estimating equations to construct multivariable logistic regression models.ResultsCompared to a referent epinephrine average dosing period of 4 to <5 min per dose, survival to hospital discharge was significantly higher in patients with the following epinephrine average dosing periods: for 6 to <7 min/dose, adjusted odds ratio [OR], 1.41 (95%CI: 1.12, 1.78); for 7 to <8 min/dose, adjusted OR, 1.30 (95%CI: 1.02, 1.65); for 8 to <9 min/dose, adjusted OR, 1.79 (95%CI: 1.38, 2.32); for 9 to <10 min/dose, adjusted OR, 2.17 (95%CI: 1.62, 2.92). This pattern was consistent for both shockable and non-shockable cardiac arrest rhythms.ConclusionLess frequent average epinephrine dosing than recommended by consensus guidelines was associated with improved survival of in-hospital cardiac arrest.
| S-EPMC4544685 | biostudies-literature
Project description:AimCompare vasopressin to a second dose of epinephrine as rescue therapy after ineffective initial doses of epinephrine in diverse models of pediatric in-hospital cardiac arrest.Methods67 one- to three-month old female swine (10-30 kg) in six experimental cohorts from one laboratory received hemodynamic-directed CPR, a resuscitation method where high quality chest compressions are provided and vasopressor administration is titrated to coronary perfusion pressure (CoPP) ≥20 mmHg. Vasopressors are given when CoPP is <20 mmHg, in sequences of two doses of 0.02 mg/kg epinephrine separated by minimum one-minute, then a rescue dose of 0.4 U/kg vasopressin followed by minimum two-minutes. Invasive measurements were used to evaluate and compare the hemodynamic and neurologic effects of each vasopressor dose.ResultsIncreases in CoPP and cerebral blood flow (CBF) were greater with vasopressin rescue than epinephrine rescue (CoPP: +8.16 [4.35, 12.06] mmHg vs. + 5.43 [1.56, 9.82] mmHg, p = 0.02; CBF: +14.58 [-0.05, 38.12] vs. + 0.00 [-0.77, 18.24] perfusion units (PFU), p = 0.005). Twenty animals (30%) failed to achieve CoPP ≥20 mmHg after two doses of epinephrine; 9/20 (45%) non-responders achieved CoPP ≥20 mmHg after vasopressin. Among all animals, the increase in CBF was greater with vasopressin (+14.58 [-0.58, 38.12] vs. 0.00 [-0.77, 18.24] PFU, p = 0.005).ConclusionsCoPP and CBF rose significantly more after rescue vasopressin than after rescue epinephrine. Importantly, CBF increased after vasopressin rescue, but not after epinephrine rescue. In the 30% that failed to meet CoPP of 20 mmHg after two doses of epinephrine, 45% achieved target CoPP with a single rescue vasopressin dose.
| S-EPMC8244440 | biostudies-literature
Project description:ObjectivesTo evaluate whether patients who experience cardiac arrest in hospital receive epinephrine (adrenaline) within the two minutes after the first defibrillation (contrary to American Heart Association guidelines) and to evaluate the association between early administration of epinephrine and outcomes in this population.DesignProspective observational cohort study.SettingAnalysis of data from the Get With The Guidelines-Resuscitation registry, which includes data from more than 300 hospitals in the United States.ParticipantsAdults in hospital who experienced cardiac arrest with an initial shockable rhythm, including patients who had a first defibrillation within two minutes of the cardiac arrest and who remained in a shockable rhythm after defibrillation.InterventionEpinephrine given within two minutes after the first defibrillation.Main outcome measuresSurvival to hospital discharge. Secondary outcomes included return of spontaneous circulation and survival to hospital discharge with a good functional outcome. A propensity score was calculated for the receipt of epinephrine within two minutes after the first defibrillation, based on multiple characteristics of patients, events, and hospitals. Patients who received epinephrine at either zero, one, or two minutes after the first defibrillation were then matched on the propensity score with patients who were "at risk" of receiving epinephrine within the same minute but who did not receive it.Results2978 patients were matched on the propensity score, and the groups were well balanced. 1510 (51%) patients received epinephrine within two minutes after the first defibrillation, which is contrary to current American Heart Association guidelines. Epinephrine given within the first two minutes after the first defibrillation was associated with decreased odds of survival in the propensity score matched analysis (odds ratio 0.70, 95% confidence interval 0.59 to 0.82; P<0.001). Early epinephrine administration was also associated with a decreased odds of return of spontaneous circulation (0.71, 0.60 to 0.83; P<0.001) and good functional outcome (0.69, 0.58 to 0.83; P<0.001).ConclusionHalf of patients with a persistent shockable rhythm received epinephrine within two minutes after the first defibrillation, contrary to current American Heart Association guidelines. The receipt of epinephrine within two minutes after the first defibrillation was associated with decreased odds of survival to hospital discharge as well as decreased odds of return of spontaneous circulation and survival to hospital discharge with a good functional outcome.
| S-EPMC4823528 | biostudies-literature
Project description:ObjectiveTo describe the clinical trial "Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest" (VAM-IHCA).MethodsThe 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.ResultsThe 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.ConclusionThe 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.
| S-EPMC8244400 | biostudies-literature
Project description:Despite its use since the 1960s, the safety or effectiveness of adrenaline as a treatment for cardiac arrest has never been comprehensively evaluated in a clinical trial. Although most studies have found that adrenaline increases the chance of return of spontaneous circulation for short periods, many studies found harmful effects on the brain and raise concern that adrenaline may reduce overall survival and/or good neurological outcome. The PARAMEDIC-2 trial seeks to determine if adrenaline is safe and effective in out-of-hospital cardiac arrest. This is a pragmatic, individually randomised, double blind, controlled trial with a parallel economic evaluation. Participants will be eligible if they are in cardiac arrest in the out-of-hospital environment and advanced life support is initiated. Exclusions are cardiac arrest as a result of anaphylaxis or life threatening asthma, and patient known or appearing to be under 16 or pregnant. 8000 participants treated by 5 UK ambulance services will be randomised between December 2014 and August 2017 to adrenaline (intervention) or placebo (control) through opening pre-randomised drug packs. Clinical outcomes are survival to 30 days (primary outcome), hospital discharge, 3, 6 and 12 months, health related quality of life, and neurological and cognitive outcomes (secondary outcomes). Trial registration (ISRCTN73485024).
| S-EPMC5081174 | biostudies-literature
Project description:Background and purposeNausea is associated with the hormonal secretion of vasopressin and adrenaline, although their actions in inducing nausea is poorly understood. Here, we have investigated their actions on human stomach muscle.Experimental approachMuscle strips were suspended in tissue baths and neuronal-/non-neuronally-mediated contractions were measured. Custom software analysed eight motility parameters defining spontaneous phasic non-neuronally mediated contractions. Receptor distributions were assessed by qPCR and immunofluorescence.Key resultsV1A receptors and α1 -adrenoceptors were located on muscle as well as interstitial cells of Cajal (ICCs). Myogenic contractions of human proximal and distal stomach (respectively, 2.6 ± 0.1 and 2.7 ± 0.0 per minute; n = 44) were larger in the distal area (1.1 ± 0.1 and 5.0 ± 0.1 mN), developing relatively slowly (proximal) or rapidly (distal). Vasopressin caused tonic (proximal) or short-lived (distal) increases in muscle tone and increased myogenic contraction amplitude, frequency and rate (acting at V1A receptors; thresholds 10-11 -10-10 M); by contrast, cholinergically mediated contractions were unaffected. Oxytocin acted similarly to vasopressin but less potently, at OT receptors). Adrenaline increased (10-10 -10-5 M; α1 -adrenoceptors) and decreased (≥10-6 M; β-adrenoceptors) muscle tone and enhanced/reduced myogenic contractions. Cholinergically mediated contractions were reduced (α2 -adrenoceptors). Combined, vasopressin (10-9 M) and adrenaline (10-8 M) increased muscle tone and phasic myogenic activity in a synergistic manner.Conclusions and implicationsVasopressin and adrenaline increased human gastric tone and myogenic contraction amplitude, rate of contraction and frequency. In combination, their actions were further increased in a synergistic manner. Such activity may promote nausea.
| S-EPMC9826163 | biostudies-literature