CCM Journal Club: Vasopressin-Epinephrine-Steroids for in hospital cardiac arrest
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Transcript of CCM Journal Club: Vasopressin-Epinephrine-Steroids for in hospital cardiac arrest
©2014 MFMER | slide-2
Background
• Single-center, prospective, randomized, double-blind, placebo-controlled, parallel-group trial of 100 consecutive patients.
• Study group had:
• More frequent ROSC
(39 of 48 [81%] vs 27 of 52 [52%]; P = .003)
• Improved survival to hospital discharge
(9 [19%] vs 2 [4%]; P = .02)
©2014 MFMER | slide-3
Background
• Rate of survival after in hospital cardiac arrest improved over recent years.
• But rates of good neurologic outcomes have not.
©2014 MFMER | slide-4
Background
• Not adequately powered for neurologic outcome.
• Only single center.
• Thus, leading the impetus for a larger, multi-centre trial.
©2014 MFMER | slide-5
Objective
• Determine if vasopressin-steroid-epinephrine during CPR improves survival to hospital discharge with a Cerebral Performance Category (CPC) Scale of 1 or 2 in vasopressor-requiring, in-hospital cardiac arrest.
©2014 MFMER | slide-6
Design
• Randomized, double-blind, placebo-controlled, parallel-group trial.
• September 1, 2008, to October 1, 2010.
• Three Greek tertiary care centers (2400 beds)
• 268 consecutive patients with cardiac arrest requiring epinephrine according to resuscitation guidelines (from 364 patients assessed for eligibility).
©2014 MFMER | slide-7
Intervention
VSE
Vasopressin (20 IU/CPR cycle) plus
Epinephrine (1 mg/CPR cycle)
Methylprednisolone(40 mg) for 1st CPR
cycle only
Control
Saline placebo plus Epinephrine (1 mg/CPR cycle)
Saline placebo for 1st CPR cycle only
For up to 5 CPR cycles only. Each CPR cycle is 3 minutes.
Shock after resuscitation was treated with stress-dose hydrocortisone
(300 mg daily for 7 days maximum and gradual taper)
©2014 MFMER | slide-8
Primary End Points
• Return of spontaneous circulation (ROSC) for 20 minutes or longer.
• Survival to hospital discharge with a Cerebral Performance Categories Scale of 1 or 2.
©2014 MFMER | slide-9
Secondary End Point
• Arterial pressure during and 15 to 20 minutes after CPR
• Intensity of post-arrest systemic inflammatory response.
• Number of organ failure–free days until completion of follow-up.
• Cerebral performance.
©2014 MFMER | slide-10
Results
• VSE did better than controls:
• ROSC of 20 minutes or longer
• 109 (84%) vs 91 (66%)
• OR ~3; 95% CI, 1.4-6.4; P = .005
• Survival to hospital discharge with CPC score of 1 or 2
• 18 (14%) vs 7 (5%)
• OR 3.3; 95% CI, 1.2-9.2; P = .02
©2014 MFMER | slide-11
Results
• VSE with post-resuscitation shock vscorresponding controls did better:
• Survival to hospital discharge with CPC scores of 1 or 2
• 16 (21%) vs 6 (8%)
• OR 3.7; 95% CI, 1.2-11.6; P = .02
• Improved hemodynamics, and less organ dysfunction.
• (?Benefit of hydrocortisone post resuscitation)
©2014 MFMER | slide-13
Paper Critique
• Relevant clinical question - yes.
• Biologically plausible – yes, backed by animal studies and extrapolated human data.
• Appropriate study population - yes.
• Adequately powered and complete - yes.
• Ethically acceptable – yes, IRB approved.
• Pre-specified and relevant end points and statistical analysis – yes, well defined ahead.
©2014 MFMER | slide-14
Paper Critique
• Randomization – good.
• Allocation concealment – good.
• Blinding – pharmacist not blinded but didn’t intervene in study.
• Bias – possible as the authors are the same as prior VSE paper.
• Intention to Treat analysis - yes.
• Follow up – 100%.
©2014 MFMER | slide-15
Paper Critique
• Protocol compliance – yes, high compliance.
• Robust statistical analysis – yes, well analyzed.
©2014 MFMER | slide-16
Strengths
• Multi-centre
• Randomized
• Pragmatic
• Robust methodology
• Adequately powered
©2014 MFMER | slide-17
Weaknesses
• Same authors!
• Impossible to decide which intervention is where the money is!
• VSE vs E
• VS vs E
• VE vs E
• SE vs S
• Or is it the tapering hydrocortisone post resuscitation?
• But hey ho! Haven’t we seen this before?
• River’s/Surviving Sepsis/Bundles!
©2014 MFMER | slide-18
Weaknesses
• Baseline characteristic not equal.
• Controls: more respiratory and metabolic causes for cardiac arrest.
• VSE: more cardiac arrests due to cardiac ischemia.
• Worse outcomes described for respiratory/metabolic causes of cardiac arrest compared to cardiac ischemia.
©2014 MFMER | slide-19
Weaknesses
• Suboptimal use of therapeutic hypothemia.
• But:
• Hypothermia (to 33 C at least) probably not helpful anyway.
©2014 MFMER | slide-20
Some thoughts
• Double blind randomized placebo-controlled trial of adrenaline in out-of-hospital cardiac arrest (534 patients). 1:1000 adrenaline vsplacebo.
• Not perfect but…
• 22 (8%) placebo vs 64 (24%) adrenaline had ROSC.
• 5 (2%) placebo vs 11 (4%) adrenaline had survival to hospital discharge (OR=2.2; 95% CI 0.7-6.3) -> not statistically significant.
©2014 MFMER | slide-21
Some thoughts
• Similarly (imperfect):
• ACLS with drug administration vs ACLS without drug administration:
• Higher rates of short-term survival
• But no statistically significant improvement in survival to hospital discharge or long-term survival.
©2014 MFMER | slide-22
Some thoughts
• Pigs. Cerebral cortical microcirculatory blood flow measured.
• Epinephrine’s alpha1-agonist action may reduce cerebral microvascular blood flow and increase the severity of cerebral ischemia during CPR.
• MAYBE: VSE resulted in less total epinephrine use, and the beneficial effect of VSE may be related to reduced harm from high doses of epinephrine.
©2014 MFMER | slide-23
Conclusion
• This study suggests that adding vasopressin and corticosteroids to epinephrine during resuscitation from in hospital cardiac arrest, and continuing steroids if shock is present, may improve outcomes
• from abysmal to just very poor.
• Best evidence available at current moment.
• (Surprisingly, <30 citations compared to TTM trial and the like).
• So VSE should be seriously considered.
©2014 MFMER | slide-24
Conclusion
• Then again…
• Given ample evidence of medical reversals, one might be forgiven for hesitating.
• Current resuscitation guidelines have not adopted the VSE approach.
• Reasonable to repeat this study for independent verification.