What is the Future of Epinephrine in Cardiac Arrest? Pros and Cons

Transcription

1 What is the Future of Epinephrine in Cardiac Arrest? Pros and Cons Melissa L. Thompson Bastin, PharmD., BCPS Komal A. Pandya, PharmD., BCPS 0 Presenter Disclosure Information Melissa L. Thompson Bastin, PharmD., BCPS Komal A. Pandya, PharmD., BCPS What is the Future of Epinephrine in Cardiac Arrest? Pros and Cons FINANCIAL DISCLOSURE: None UNLABELED/UNAPPROVED USES DISCLOSURE: None 1 1

2 Learning Objectives Identify the goals of ACLS and role of adrenergic agents Appreciate the historical data regarding adrenergic agent selection, dose and current recommendations List the proposed changes to the current guidelines Understand the basis of the recommended changes Recognize the controversy that exists with the proposed changes 2 Melissa L. Thompson Bastin, PharmD., BCPS EPINEPHRINE: A HISTORICAL PERSPECTIVE 3 2

3 Goals of ACLS Maintain a minimum cerebral perfusion pressure and diastolic perfusion pressure ROSC Neurologic recovery High quality CPR Push Hard: 2 inch depth of the chest, allowing for full chest recoil Push Fast: At least 100/min Monitor Quality: EtCO2 >10 mmhg or diastolic arterial pressure >20 mmhg The best compressions provide 10-15% CPP Vasoactive agents: Epinephrine IV/IO 1mg every 3-5minutes Vasopressin IV/IO 40 units x1, to replace the first or second dose of epinephrine Future cardiology 2010;6(4): Circulation 2010; 122: S Mean CPP difference: *P<0.05; P<0.01; P<

4 Why Epinephrine Non selective agonist at the α 1,α 2 β 1, β 2 adrenergic receptors α 1 -receptors arteriolar vasoconstriction, positive inotropic, chronotropic effects, may induce coronary vasoconstriction α 2 -receptors mediate venoconstriction (relaxation) β 1 -and β 2 -receptors induce positive inotropic and chronotropiceffects, vasodilatation of the coronaries Most potent vasoconstrictor Increase in CO, SVR, HR, positive inotropic effects >> NE or DA Increased DO 2, MVO 2 Increases ATP consumption by the Na + -K + -ATPase activity in skeletal muscles Stimulates muscle glycolysis and lactate production Epinephrine Agent α 1 α 2 β 1 β 2 DA mcg/kg/min >0.05 mcg/kg/min Norepinephrine /++ 0 Phenylephrine Future cardiology 2010;6(4): Am J Respir Crit Care Med 2011;183: History of adrenaline Critical Care Medicine 1979;7(7):

5 Epinephrine earliest use dates back to 1896 utilized to restore circulation to measureable levels when collapse was induced by chloral hydrate Early concerns for epinephrine causing or worsening ventricular arrhythmias in the setting of ventricular fibrillation Doses utilized in cardiac arrest were 0.2 to 0.3mg Often given with procaine to prevent inducible ventricular arrhythmias Anesthesia and Analgesia 1963;42(5): Significant increase in aortic diastolic pressure (ADR), coronary perfusion pressure (CPP) from baseline MBF, DO 2 and MVO 2 also increased from baseline with both NE and Epi NE >> Epi at higher doses (0.2mg/kg) but with significant increase in MVO 2 NE as effective as Epi, higher doses associated with lower resuscitation rates and proportional increase in MVO 2 Resuscitation 1990;19(3):

6 Fig. 1. OR and 95% CI for ROSC Fig. 3. OR and 95% CI for hospital discharge Resuscitation 2000;40: Lancet 2001; 358:

7 Minerva Anestesiol 2014;80: Critical Care 2014, 18:463 Figure 2. Forest plot of pooling of pre-hospital adrenaline effects on Figure 3. Forest plot of pooling of prehospital adrenaline effects on prehospital ROSC. AD, adrenaline; N, number of subjects; Non-AD, non overall ROSC. AD, adrenaline; N, number of subjects; Non-AD, non adrenaline; ROSC, return of spontaneous circulation; RR, risk ratio. adrenaline; ROSC, return of spontaneous circulation; RR, risk ratio. 7

8 Large Japanese observational cohort ROSC and improved one-month survival Nonshockable rhythm: NNT 6, significance driven when epi <20 min Shockable rhythm: Overall lower ROSC, one-month survival However when epi <9 min, improved ROSC [OR 1.45(1.20 to 1.75)]; onemonth survival equivocal [OR 0.95(0.77 to 1.16)] Worse neurologic outcome scores when administration time >10min for any rhythm Critical Care 2014, 18:463 Summary Epinephrine seems to be preferred vasoactive agent from animal models Best studied dose is 1mg May be associated with ROSC in out of hospital cardiac arrest (OHCA) Timing 15 8

9 Komal. A. Pandya, PharmD., BCPS PROPOSED ACLS GUIDELINES UPDATES 16 Vasopressors for Cardiac Arrest: Epinephrine vs. Placebo Question: Does use of epinephrine, compared with placebo or not using epinephrine, change survival with favorable neurological / functional outcome? Recommendation: Standard dose epinephrine should be administered to patients in cardiac arrest (weak, low quality)

10 Epinephrine vs. Placebo Design:double-blind, randomized, placebo controlled trial Setting: Out of hospital, Australia, multi-center Outcomes: Survival to hospital discharge (primary) Pre-hospital ROSC Neurologic outcome Jacobs et al. Resus : Epinephrine vs. Placebo Jacobs et al. Resus :

11 Epinephrine vs. Placebo Limitations: Out of hospital only Did not meet power Unable to assess CPR quality Selection bias Did not address etiology of cardiac arrest Quality of outcomes assessed Jacobs et al. Resus : Vasopressors for Cardiac Arrest: Epinephrine vs. High Dose Epinephrine Question: Does high dose epinephrine compared with standard dose epinephrine change survival with good neurological outcome? Recommendation: Against HDE (strong, moderate quality)

12 Epinephrine vs. High Dose Epinephrine Pro s of Cited Studies Con s of Cited Studies Brown et al. NEJM : Sherman et al. Pharmacother (2): Stiell et al. NEJM (15): Gueugniaud et al. NEJM : Choux et al. Resus : 3-9. Callaham et al. JAMA (19): Vasopressors for Cardiac Arrest: Epinephrine vs. Vasopressin Question: Does use of epinephrine compared with vasopressin change outcomes? Recommendation: Against initiating vasopressin as a substitution for epinephrine in the treatment of cardiac arrest (weak, low quality)

13 Epinephrine vs. Vasopressin Design:prospective, RCT Setting: OHCA, Japan, single-center Primary Outcome: Favorable neurological outcome Treatment Groups: Epinephrine 1mg (max of 4mg) Vasopressin 40 IU (max of 160 IU) Mukoyama et al. Resus : Epinephrine vs. Vasopressin Mukoyama et al. Resus :

14 Vasopressors for Cardiac Arrest: Epinephrine vs. Epinephrine / Vasopressin Question: Does use of epinephrine compared with vasopressin change outcomes? Recommendation: Against adding vasopressin to standard dose epinephrine during cardiac arrest (weak, moderate quality) 26 Epinephrine vs. Epinephrine / Vasopressin Survival to hospital discharge (5 RCT) SDE versus combination therapy No difference in achievement Survival to hospital discharge w/ favorable neurologic outcome (3 RCT) SDE versus combination therapy No difference in achievement Gueugniad et al. NEJM (1): Ong et al. Resus (8): Wenzel et al. NEJM (2): Ducros et al. J EM (5): Lindner et al. Lancet : Callaway et al. Am J Card :

15 Epinephrine vs. Epinephrine / Vasopressin Survival to hospital admission (5 RCT) No significant difference ROSC (6 RCT) No advantage of combination therapy Gueugniad et al. NEJM (1): Ong et al. Resus (8): Wenzel et al. NEJM (2): Ducros et al. J EM (5): Lindner et al. Lancet : Callaway et al. Am J Card : Epinephrine vs. Epinephrine / Vasopressin Pro s of Cited Studies Con s of Cited Studies Gueugniad et al. NEJM (1): Ong et al. Resus (8): Wenzel et al. NEJM (2): Ducros et al. J EM (5): Lindner et al. Lancet : Callaway et al. Am J Card :

16 Studies NOT Considered 30 Future Direction & Considerations Does the existing data represent the patients that we take care of? What would an ideal study look like if we wanted to get a clear answer on what drugs are helpful during ACLS? What endpoints would we examine in these studies? 31 16

17 Questions? What is the future of epinephrine in cardiac arrest? 32 17