• Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial

    by Alan Batt. Last modified: 28/02/14

    vse

    Summary

    • Randomized, double-blind, placebo-controlled, multi-centred, parallel-group trial
    • 268 patients in cardiac arrest enrolled
    • Patients were from ICU, CCU, ED, general wards and operating department (15% from ED)
    • Mean age 63 in both groups with the majority being men.
    • 100% follow-up
    • Intervention group (n=130) received vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) and methylprednisolone (40 mg, 1st cycle of CPR)
      • Survivors in intervention group (n=76) received stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper)
    • Control group received (n=138) received saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) and saline placebo (1st cycle of CPR)
      • Survivors in control group (n=73) received saline placebo
    • Patients in the intervention group had higher probability for ROSC of 20 minutes or longer and survival to hospital discharge with CPC score of 1 or 2.
    • Patients in the intervention group with postresuscitation shock had higher probability for survival to hospital discharge with CPC scores of 1 or 2, improved hemodynamics and central venous oxygen saturation, and less organ dysfunction.
    • Adverse event rates were similar in the 2 groups.

    Whilst a well-designed and executed clinical trial, some limitations of this study for prehospital application include:

    • The study was carried out on hospital patients and not on a prehospital population.
    • The control group were in hospital for a shorter mean duration before arrest – possibly more rapidly progressing pathology.
    • The control group had more underlying respiratory depression/failure and metabolic causes of arrest while the intervention group had more myocardial ischaemia/infarct related arrests – outcomes from respiratory arrests are generally poorer.
    • Recommendations from ILCOR regarding therapeutic hypothermia post ROSC were not adequately implemented in either group.
    • CPR quality was not adequately assessed, and this can vary wildly between clinical settings due to exposure to cardiac arrest (or lack thereof).

    cpcscale

     
    Mentzelopoulos SD1, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, Kolliantzaki I, Theodoridi M, Ischaki H, Makris D, Zakynthinos E, Zintzaras E, Sourlas S, Aloizos S, Zakynthinos SG. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013 Jul 17;310(3):270-9. PMID: 23860985.

    Abstract

    Importance

    Among patients with cardiac arrest, preliminary data have shown improved return of spontaneous circulation and survival to hospital discharge with the vasopressin-steroids-epinephrine (VSE) combination.

    Objective

    To determine whether combined vasopressin-epinephrine during cardiopulmonary resuscitation (CPR) and corticosteroid supplementation during and after CPR improve survival to hospital discharge with a Cerebral Performance Category (CPC) score of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest.

    Design, Setting & Participants

    Randomized, double-blind, placebo-controlled, parallel-group trial performed from September 1, 2008, to October 1, 2010, in 3 Greek tertiary care centers (2400 beds) with 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility).

    Interventions

    Patients received either vasopressin (20 IU/CPR cycle) plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (VSE group, n = 130) or saline placebo plus epinephrine (1 mg/CPR cycle; cycle duration approximately 3 minutes) (control group, n = 138) for the first 5 CPR cycles after randomization, followed by additional epinephrine if needed. During the first CPR cycle after randomization, patients in the VSE group received methylprednisolone (40 mg) and patients in the control group received saline placebo. Shock after resuscitation was treated with stress-dose hydrocortisone (300 mg daily for 7 days maximum and gradual taper) (VSE group, n = 76) or saline placebo (control group, n = 73).

    Main outcomes & measures

    Return of spontaneous circulation (ROSC) for 20 minutes or longer and survival to hospital discharge with a CPC score of 1 or 2.

    Results

    Follow-up was completed in all resuscitated patients. Patients in the VSE group vs patients in the control group had higher probability for ROSC of 20 minutes or longer (109/130 [83.9%] vs 91/138 [65.9%]; odds ratio [OR], 2.98; 95% CI, 1.39-6.40; P = .005) and survival to hospital discharge with CPC score of 1 or 2 (18/130 [13.9%] vs 7/138 [5.1%]; OR, 3.28; 95% CI, 1.17-9.20; P = .02). Patients in the VSE group with postresuscitation shock vs corresponding patients in the control group had higher probability for survival to hospital discharge with CPC scores of 1 or 2 (16/76 [21.1%] vs 6/73 [8.2%]; OR, 3.74; 95% CI, 1.20-11.62; P = .02), improved hemodynamics and central venous oxygen saturation, and less organ dysfunction. Adverse event rates were similar in the 2 groups.

    Conclusion and relevance

    Among patients with cardiac arrest requiring vasopressors, combined vasopressin-epinephrine and methylprednisolone during CPR and stress-dose hydrocortisone in postresuscitation shock, compared with epinephrine/saline placebo, resulted in improved survival to hospital discharge with favorable neurological status.

    Trial Registration

    clinicaltrials.gov Identifier: NCT00729794.

    References

     
    1.

    Mentzelopoulos SD1, Malachias S, Chamos C, Konstantopoulos D, Ntaidou T, Papastylianou A, Kolliantzaki I, Theodoridi M, Ischaki H, Makris D, Zakynthinos E, Zintzaras E, Sourlas S, Aloizos S, Zakynthinos SG. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013 Jul 17;310(3):270-9. PMID: 23860985.

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    Alan Batt

    Alan Batt

    Paramedic, educator, researcher
    Alan is a critical care paramedic, paramedic educator and prehospital researcher, currently working around the world as an educator and researcher. He has previously worked and studied across Europe, North America and the Middle East. He holds a Graduate Certificate in Intensive Care Paramedic Studies, and an MSc in Critical Care. His main interests are in care of the elderly, end-of-life care, patient safety, professionalism (including role and identity), and paramedic education.

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