Drugs are a waste of time - Resuscitation Council (UK)...Drugs are a waste of time Jerry Nolan Royal United Hospital, Bath, UK Where are drugs on the chain of survival?\爀屲Max 10
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Drugs are a waste of time Jerry Nolan Royal United Hospital, Bath, UK
A total of 16,221 out-of-hospital cardiac arrests were attended by 74 Emergency Medical Services agencies There was a considerable variability in the administration of amiodarone and lidocaine for the treatment of shock resistant ventricular tachycardia/ventricular fibrillation. For non-shockable rhythms, atropine use ranged from 29 to 95% and sodium bicarbonate use ranged from 0.2 to 73% across agencies in the 89% of agencies that used the drug. Epinephrine use ranged from 57 to 98% within agencies. Neither lidocaine nor amiodarone was associated with a survival benefit while there was an inverse relationship between the administration of epinephrine, atropine and sodium bicarbonate and survival to hospital discharge.
Nichol G. NEJM 2015;373:2203–14
Presenter
Presentation Notes
Recruitment period 2011–2015
Andersen LW. JAMA 2017;317:494–506
AHA Get with the Guidelines-R Registry
89% of patients received epinephrine
Ontario Prehospital Advanced Life Support (OPALS) Phase III
P<0.001
P=0.83
Stiell IG. N Engl J Med 2004;351:647-56
Drugs administered to 3742 in ALS phase (1998–2002)
Presenter
Presentation Notes
The effect of adding adrenaline to CPR protocols can be inferred from the excellent studies that have been undertaken in Ontario. BLS-D was optimised JAMA 1999 = rapid defibrillation response interval of 8 minutes or less in 90% of patients with cardiac arrest Main ALS interventions were intubation and IV drugs. Survival to hospital admission is higher but there is no difference in survival to discharge
Odds ratios for survival to hospital discharge: OPALS Stiell IG. N Engl J Med 2004;351:647-56
Presenter
Presentation Notes
The OPALS studies have shown benefit for early CPR and early defibrillation but not for intubation/drugs
Randomized
and included
(n=851)
IV (n=418)
ROSC n= 165
40%
Adm. ICU n=125
30%
Discharged n= 44
10.5%
No IV (n=433)
ROSC n= 107
25%
Adm. ICU n= 88
21%
Discharged n= 40
9.2%
P<0.001 P=0.002 P=0.756
Olasveengen TM. JAMA 2009;302:2222-9
Presenter
Presentation Notes
IV access allowed in control group only after 5 min ROSC. Primary outcome was survival to hospital discharge
Hagihara A. JAMA 2012;307:1161-8 Whole of Japan - 2005 -2008 417 188 cases analysed; 15 030 received epinephrine; 13 401 propensity-matched pairs
Andersen LW. BMJ 2016;353:i1577
• 2978 patients matched on propensity score • 1510 (51%) received epinephrine within 2 min after first defibrillation
Prehospital Assessment of the Role of Adrenaline: Measuring the Effectiveness of Drug administration In Cardiac arrest Placebo versus adrenaline in out-of-
hospital cardiac arrest Primary end point 30-day survival 6400 recruited from 8000 Estimated finish Aug 2017
24.6
36.3
9.9
2831.2
9.9
05
10152025303540
ROSC Hospitaladmission
Hospitaldischarge
Per
cen
t
Vasopressin (n=589)Adrenaline (n=597)P=0.19
P=0.06 Wenzel V. NEJM 2004;350:105-13
Presenter
Presentation Notes
Primary outcome of hospital admission = no difference (remember powered to detect a difference of 25%). Hospital discharge rates – the secondary end point are identical.
Kudenchuk PJ. NEJM 2016;374:1711–22
Presenter
Presentation Notes
Drug given after failure of one or more shocks
Vukmir RB. Am J Emerg Med 2006;24:156–61 Bicarbonate 50 mmoL Primary end-point survival to ED?
Bicarbonate (n=420)
Saline (n=372)
P
Survival to ED n (%) all 58 (13.8) 52 (14.0) N Survival to ED – resuscitation duration 0–15 min (n = 499) n (%)
39 (14.9) 44 (18.6)
Survival to ED – resuscitation duration > 15 min (n = 293) n (%)
19 (13.6) 8 (6.3)
Presenter
Presentation Notes
Double-blind RCT; primary outcome ROSC? Patients received standard advanced cardiac life support (ACLS) protocol including chest compressions, ventilation, defibrillation, epinephrine (0.01 mg/kg), atropine (0.01 mg/kg), and antiarrhythmics or pressor agents, as warranted. All patients were randomized to a treatment group receiving an empirical dose of bicarbonate (Abbott Laboratories, Chicago, Ill) 1 ample (50 mEq/L) early in the arrest cycle or the control group who received an equal amount of normal saline in a double-blinded fashion to clarify the benefits of the osmolar load vs base deficit correction.
Deakin CD. Resuscitation 2010;81S:e93–e174
Deakin CD. Resuscitation 2011;81S:e93–e174
Post cardiac arrest shock Hydrocortisone (100 mg tds
for 7d) or placebo (n=50) No difference in shock
reversal or other outcomes
Donnino M. Critical Care 2016;20:82
24 h
Presenter
Presentation Notes
Background: The purpose of this study was to determine whether the provision of corticosteroids improves time to shock reversal and outcomes in patients with post-cardiac arrest shock. Methods: We conducted a randomized, double-blind trial of post-cardiac arrest patients in shock, defined as vasopressor support for a minimum of 1 hour. Patients were randomized to intravenous hydrocortisone 100 mg or placebo every 8 hours for 7 days or until shock reversal. The primary endpoint was time to shock reversal. Results: Fifty patients were included with 25 in each group. There was no difference in time to shock reversal between groups (hazard ratio: 0.83 [95 % CI: 0.40–1.75], p = 0.63). We found no difference in secondary outcomes including shock reversal (52 % vs. 60 %, p = 0.57), good neurological outcome (24 % vs. 32 %, p = 0.53) or survival to discharge (28 % vs. 36 %, p = 0.54) between the hydrocortisone and placebo groups. Of the patients with a baseline cortisol < 15 ug/dL, 100 % (6/6) in the hydrocortisone group achieved shock reversal compared to 33 % (1/3) in the placebo group (p = 0.08). All patients in the placebo group died (100 %; 3/3) whereas 50 % (3/6) died in the hydrocortisone group (p = 0.43). Conclusions: In a population of cardiac arrest patients with vasopressor-dependent shock, treatment with hydrocortisone did not improve time to shock reversal, rate of shock reversal, or clinical outcomes when compared to placebo.
Intensive Care Med 2017, on line
Presenter
Presentation Notes
Exenatide = Glucagon-like peptide-1 analog
Kudenchuk PJ. Resuscitation 2013;84:861–2
Cariou A. J Am Coll Cardiol 2016;68:40–9
476 comatose post-OHCA patients, France
5 x 40,000 units EPO over 48 h Primary end point CPC 1 at
60 days
Presenter
Presentation Notes
RESULTS In total, 476 patients were included in the primary analysis. Baseline characteristics were similar in the 2 groups. At day 60, 32.4% of patients (76 of 234) in the intervention group reached a CPC 1 level, as compared with 32.1% of patients (78 of 242) in the control group (odds ratio: 1.01; 95% confidence interval: 0.68 to 1.48). The mortality rate and proportion of patients in each CPC level did not differ at any time points. Serious adverse events were more frequent in Epo-treated patients as compared with controls (22.6% vs. 14.9%; p . 0.03), particularly thrombotic complications (12.4% vs. 5.8%; p . 0.01).
We randomly assigned 120 consecutive comatose patients resuscitated from OHCA in a double-blind, 2-center trial. They were administered 17.4 μg exenatide (Byetta) or placebo over a 6-hour and 15-minute infusion, in addition to standardized intensive care including targeted temperature management. The coprimary end points were feasibility, defined as initiation of the study drug in >90% patients within 240 minutes of return of spontaneous circulation, and efficacy, defined as the geometric area under the neuron-specific enolase curve from 24 to 72 hours after admission. The main secondary end points included a composite end point of death and poor neurological function, defined as a Cerebral Performance Category score of 3 to 5 assessed at 30 and 180 days.
Argaud L. JAMA Cardiol 2016;1:557-565
794 OHCAs France Cyclosporine 2.5 mg/kg
during ACLS Primary end point
Sequential Organ Failure Assessment (SOFA) score at 24 h
Drugs are a waste of time
No high-quality evidence that any drug improves long-term outcome after cardiac arrest
Adrenaline increase rates of ROSC but its impact on long-term outcome is unknown
