Therapeutics
Combined vasopressin, steroids, and epinephrine improved survival in in-hospital cardiac arrest
Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013; 310:270-9.
Clinical impact ratings: E ★★★★★★✩ h ★★★★★✩✩ C ★★★★★✩✩ c ★★★★★★✩ Question
Main results
In patients with in-hospital, vasopressor-requiring cardiac arrest, does adding a combination of vasopressin, steroids, and epinephrine (VSE) to cardiopulmonary resuscitation (CPR) improve survival with favorable neurologic status?
Combined VSE increased the proportion of patients who had ROSC for ≥ 20 minutes and who survived to discharge with favorable neurologic recovery compared with control (Table).
Methods
Adding a combination of vasopressin, steroids, and epinephrine to cardiopulmonary resuscitation improved survival with favorable neurologic status in patients with in-hospital cardiac arrest requiring vasopressor therapy.
Design: Randomized controlled trial (RCT). ClinicalTrials.gov NCT00729794. Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, {data collectors, and outcome assessors}†). Follow-up period: {Hospital discharge, or 60 days if discharged before 60 days.}† Setting: 3 tertiary care centers in Greece. Patients: 300 adults ≥ 18 years of age (mean age 63 y, 68% men) who had in-hospital, vasopressor-requiring cardiac arrest. Exclusion criteria included life expectancy < 6 weeks, do-not-resuscitate status, cardiac arrest due to exsanguination, cardiac arrest before hospitalization, or treatment with IV corticosteroids before cardiac arrest. Intervention: VSE combination (n = 146) or control (n = 154). VSE comprised vasopressin, 20 IU/CPR cycle up to 100 IU total, added to epinephrine, 1 mg/CPR cycle, for the first 5 CPR cycles after enrollment, and methylprednisolone sodium succinate, 40 mg, for the first CPR cycle after enrollment. If return of spontaneous circulation (ROSC) was not achieved at the end of 5 CPR cycles, CPR was continued in accordance with 2005 resuscitation guidelines, and advanced life support was conducted according to current standards. VSE patients who survived to 4 hours after resuscitation and had postresuscitation shock received stress-dose hydrocortisone, 300 mg/d for ≤ 7 days and gradual taper, and patients with evidence of acute myocardial infarction received stress-dose hydrocortisone for ≤ 3 days. The control group received the same CPR and epinephrine protocol with placebos for vasopressin and methylprednisolone. Outcomes: ROSC for ≥ 20 minutes and survival to discharge with favorable neurologic recovery (Glasgow–Pittsburgh Cerebral Performance Category score of 1 or 2). Patient follow-up: 89% (intention-to-treat analysis). VSE vs epinephrine alone (control) added to CPR in patients with in-hospital cardiac arrest‡ Outcomes
VSE
Control
RBI (95% CI)
NNT (CI)
ROSC for ≥ 20 min
84%
66%
29% (11 to 40)
6 (4 to 15)
Survival to discharge with favorable neurologic recovery§
14%
194% (16 to 549)
11 (4 to 123)
5.1%
‡CPR = cardiopulmonary resuscitation; ROSC = return of spontaneous circulation; VSE = combination of vasopressin, steroids, and epinephrine; other abbreviations defined in Glossary. RBI, NNT, and CI calculated from control event rates and odds ratios in article. §Glasgow–Pittsburgh Cerebral Performance Category score of 1 or 2.
JC4
© 2013 American College of Physicians
Conclusion
*See Glossary. †Information provided by author.
Sources of funding: Greek Society of Intensive Care Medicine and Project “Synergasia” of the Greek Ministry of Education. For correspondence: Dr. S.D. Mentzelopoulos, Evaggelismos General Hospital, Athens, Greece. E-mail [email protected]. ■
Commentary The survival rate after in-hospital sudden cardiac arrest requiring vasopressors is dismal. Multiple interventions have failed to improve survival. Vasopressin is a potent cerebral vasoconstrictor with potential to improve outcomes; however, after more than a decade of research, its effect is still unclear (1). Current American Heart Association Advanced Cardiac Life Support (ACLS) guidelines offer vasopressin as an alternative to epinephrine. The carefully conducted RCT by Mentzelopoulos and colleagues further complicates this issue. The authors speculate that methylprednisolone may enhance the vasopressor effects of vasopressin and epinephrine and reduce the postresuscitation inflammatory response. A previous small study by the same investigators found improved survival with the VSE combination in refractory arrest (2). In the current study of inpatients with cardiac arrest who required vasopressors by current ACLS guidelines, there was a nearly 9% absolute improvement in survival to neurologically intact hospital discharge (number needed to treat of 11) with VSE compared with epinephrine. This remarkable finding will need to be confirmed in other settings before it becomes standard practice. Further studies are also needed to determine whether steroids confer any additional benefit. For now, given that vasopressorrequiring CPR survival to discharge is around 5%, practitioners can consider using VSE in appropriate patients. It remains to be seen if this study will change ACLS guidelines for 2015. Kenneth A. Ballew, MD, MS University of Virginia Charlottesville, Virginia, USA References 1. Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21-30. 2. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169:15-24.
19 November 2013 | ACP Journal Club | Volume 159 • Number 10
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/928838/ by a Tufts University User on 07/27/2017
Combined vasopressin, steroids, and epinephrine improved survival in in-hospital cardiac arrest
Mentzelopoulos SD, Malachias S, Chamos C, et al. Vasopressin, steroids, and epinephrine and neurologically favorable survival after in-hospital cardiac arrest: a randomized clinical trial. JAMA. 2013; 310:270-9.
Clinical impact ratings: E ★★★★★★✩ h ★★★★★✩✩ C ★★★★★✩✩ c ★★★★★★✩ Question
Main results
In patients with in-hospital, vasopressor-requiring cardiac arrest, does adding a combination of vasopressin, steroids, and epinephrine (VSE) to cardiopulmonary resuscitation (CPR) improve survival with favorable neurologic status?
Combined VSE increased the proportion of patients who had ROSC for ≥ 20 minutes and who survived to discharge with favorable neurologic recovery compared with control (Table).
Methods
Adding a combination of vasopressin, steroids, and epinephrine to cardiopulmonary resuscitation improved survival with favorable neurologic status in patients with in-hospital cardiac arrest requiring vasopressor therapy.
Design: Randomized controlled trial (RCT). ClinicalTrials.gov NCT00729794. Allocation: Concealed.* Blinding: Blinded* (patients, clinicians, {data collectors, and outcome assessors}†). Follow-up period: {Hospital discharge, or 60 days if discharged before 60 days.}† Setting: 3 tertiary care centers in Greece. Patients: 300 adults ≥ 18 years of age (mean age 63 y, 68% men) who had in-hospital, vasopressor-requiring cardiac arrest. Exclusion criteria included life expectancy < 6 weeks, do-not-resuscitate status, cardiac arrest due to exsanguination, cardiac arrest before hospitalization, or treatment with IV corticosteroids before cardiac arrest. Intervention: VSE combination (n = 146) or control (n = 154). VSE comprised vasopressin, 20 IU/CPR cycle up to 100 IU total, added to epinephrine, 1 mg/CPR cycle, for the first 5 CPR cycles after enrollment, and methylprednisolone sodium succinate, 40 mg, for the first CPR cycle after enrollment. If return of spontaneous circulation (ROSC) was not achieved at the end of 5 CPR cycles, CPR was continued in accordance with 2005 resuscitation guidelines, and advanced life support was conducted according to current standards. VSE patients who survived to 4 hours after resuscitation and had postresuscitation shock received stress-dose hydrocortisone, 300 mg/d for ≤ 7 days and gradual taper, and patients with evidence of acute myocardial infarction received stress-dose hydrocortisone for ≤ 3 days. The control group received the same CPR and epinephrine protocol with placebos for vasopressin and methylprednisolone. Outcomes: ROSC for ≥ 20 minutes and survival to discharge with favorable neurologic recovery (Glasgow–Pittsburgh Cerebral Performance Category score of 1 or 2). Patient follow-up: 89% (intention-to-treat analysis). VSE vs epinephrine alone (control) added to CPR in patients with in-hospital cardiac arrest‡ Outcomes
VSE
Control
RBI (95% CI)
NNT (CI)
ROSC for ≥ 20 min
84%
66%
29% (11 to 40)
6 (4 to 15)
Survival to discharge with favorable neurologic recovery§
14%
194% (16 to 549)
11 (4 to 123)
5.1%
‡CPR = cardiopulmonary resuscitation; ROSC = return of spontaneous circulation; VSE = combination of vasopressin, steroids, and epinephrine; other abbreviations defined in Glossary. RBI, NNT, and CI calculated from control event rates and odds ratios in article. §Glasgow–Pittsburgh Cerebral Performance Category score of 1 or 2.
JC4
© 2013 American College of Physicians
Conclusion
*See Glossary. †Information provided by author.
Sources of funding: Greek Society of Intensive Care Medicine and Project “Synergasia” of the Greek Ministry of Education. For correspondence: Dr. S.D. Mentzelopoulos, Evaggelismos General Hospital, Athens, Greece. E-mail [email protected]. ■
Commentary The survival rate after in-hospital sudden cardiac arrest requiring vasopressors is dismal. Multiple interventions have failed to improve survival. Vasopressin is a potent cerebral vasoconstrictor with potential to improve outcomes; however, after more than a decade of research, its effect is still unclear (1). Current American Heart Association Advanced Cardiac Life Support (ACLS) guidelines offer vasopressin as an alternative to epinephrine. The carefully conducted RCT by Mentzelopoulos and colleagues further complicates this issue. The authors speculate that methylprednisolone may enhance the vasopressor effects of vasopressin and epinephrine and reduce the postresuscitation inflammatory response. A previous small study by the same investigators found improved survival with the VSE combination in refractory arrest (2). In the current study of inpatients with cardiac arrest who required vasopressors by current ACLS guidelines, there was a nearly 9% absolute improvement in survival to neurologically intact hospital discharge (number needed to treat of 11) with VSE compared with epinephrine. This remarkable finding will need to be confirmed in other settings before it becomes standard practice. Further studies are also needed to determine whether steroids confer any additional benefit. For now, given that vasopressorrequiring CPR survival to discharge is around 5%, practitioners can consider using VSE in appropriate patients. It remains to be seen if this study will change ACLS guidelines for 2015. Kenneth A. Ballew, MD, MS University of Virginia Charlottesville, Virginia, USA References 1. Gueugniaud PY, David JS, Chanzy E, et al. Vasopressin and epinephrine vs. epinephrine alone in cardiopulmonary resuscitation. N Engl J Med. 2008;359:21-30. 2. Mentzelopoulos SD, Zakynthinos SG, Tzoufi M, et al. Vasopressin, epinephrine, and corticosteroids for in-hospital cardiac arrest. Arch Intern Med. 2009;169:15-24.
19 November 2013 | ACP Journal Club | Volume 159 • Number 10
Downloaded From: https://annals.org/pdfaccess.ashx?url=/data/journals/aim/928838/ by a Tufts University User on 07/27/2017
