The use of adrenaline and long-term survival in cardiopulmonary resuscitation following cardiac arrest
Date First Published:
May 8, 2012
Last Updated:
April 17, 2013
Report by:
Craig Miller, 4th Year Medical Student (University of Southampton, Southampton, UK)
Search checked by:
Jerry Nolan, University of Southampton, Southampton, UK
Three-Part Question:
In [patients receiving cardiopulmonary resuscitation following cardiac arrest], is [the use of adrenaline beneficial] in [improving long-term survival]?
Search Strategy:
Ovid MEDLINE(R) 1946 to December Week 4 2012
Search Details:
({(CPR.mp. OR exp cardiopulmonary resuscitation/OR internal cardiac massage.mp. OR chest compressions.mp.) AND (adrenaline.mp. OR exp epinephrine/) AND (survival.mp. OR mortality.mp.)} LIMIT to (human)) 209 records.<br><br>The Cochrane Library issue 12 of 12 2012
MeSH descriptor: (Cardiopulmonary Resuscitation) explode all trees AND MESH descriptor: (Epinephrine) this term only 23 records no unique data.
MeSH descriptor: (Cardiopulmonary Resuscitation) explode all trees AND MESH descriptor: (Epinephrine) this term only 23 records no unique data.
Outcome:
wo hundred and nine papers were found of which 202 were irrelevant or of insufficient quality for inclusion. The remaining seven papers are shown in the table
Relevant Paper(s):
| Study Title | Patient Group | Study type (level of evidence) | Outcomes | Key results | Study Weaknesses |
|---|---|---|---|---|---|
| Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest. Hagihara A, Hasegawa M, Abe T. 2012 Japan | 417,188 OHCAs occurring between 2005-2008 in Japan with or without use of adrenaline in the pre-hospital phase. | Retrospective cohort study with concurrent control group | Return of spontaneous circulation before hospital arrival | No adrenaline: 5.7%, Adrenaline: 18.5% (p=0.001, OR 2.36) | Observational study, not random allocation, subject to selection bias and confounding factors. In-hospital resuscitation data not used, 1-month survival influenced by in-hospital care which varies between centres. |
| 1-month survival | No adrenaline: 4.7%, Adrenaline 5.3% (OR 0.46) | ||||
| Survival with Cerebral Performance Category (CPC) 1 or 2 | No adrenaline: 2.2%, Adrenaline 1.4% (OR 0.36) | ||||
| Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference? Herlitz J, Ekström L, Wennerblom B. 1995 Sweden | 1203 patients either received adrenaline or not, following OHCA with VF on first ECG recording. Took place in Goteborg (Sweden) between October 1980 to December 1992. 417 (35%) patients received adrenaline. | Retrospective cohort study with concurrent control group | ROSC | No adrenaline: 21%, Adrenaline: 37% (p=0.001) | Patient demographics differed between two groups. Long-term survival not given and neurological status was not indicated or assessed in those that were discharged. Small sample size with potential for type 2 error. Long study period with changes in equipment and protocol. Could not account for quality of post resuscitation care. No randomisation thus subject to selection bias. |
| Hospitalised alive | No adrenaline: 22%, Adrenaline: 31% (p=0.01) | ||||
| Discharged alive | No adrenaline: 6%, Adrenaline: 9% | ||||
| Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden. Holmberg M, Holmberg S, Herlitz J. 2002 Sweden | 10,966 cases of OHCA over a 5 year period. 42.4% treated with adrenaline | Prospective observational cohort study | 1-month survival | No adrenaline: 6.3%, Adrenaline: 3.4% (p<0.0001) | No detailed information concerning neurological status at discharge, and ROSC. Significant differences between two study groups with no randomisation, thus can’t assume two groups are comparable. No control over correct indication for adrenaline, ambulance crew proficiency and compliance to guidelines. No information concerning post-resuscitation care. |
| Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial. Jacobs IG, Finn JC, Jelinek GA, et al. 2011 Australia | 534 OHCA of which 262 in placebo group and 272 in adrenaline (given according to Australian Resuscitation Council recommendations). Groups matched for baseline characteristics. |
Placebo controlled RCT | Survival to hospital discharge | Placebo: 1.9% (n=5), Adrenaline: 4% (11). (OR 2.2, 95% CI 0.7-6.3) | Underpowered study with regard to survival to hospital discharge. Quality and timing of CPR and adrenaline administration not possible. Paramedic participation was voluntary thus only 40% of possible patients recruited. |
| Pre-hospital ROSC (>30s) | Placebo: 8.4% (22), Adrenaline 23.5% (64). (OR 3.4, 95% CI 2.0-5.6) | ||||
| CPC at hospital discharge | 2 patients in the adrenaline group had CPC score below 1-2. | ||||
| Outcome when adrenaline (epinephrine) was actually given vs. not given - post hoc analysis of a randomized clinical trial. Olasveengen TM, Wik L, Sunde K, et al. 2012 Norway | 848 OHCA with 387 (45.6%) given adrenaline vs. 481 (54.4%) no adrenaline given. | Retrospective analysis of RCT | Admission to hospital alive with ROSC | No adrenaline: 27%, Adrenaline: 48% (OR 2.5, p<0.001) | Confounders not fully adjusted as time points for adrenaline administration and ROSC unreliable. Single centre study. |
| Discharge from hospital | No adrenaline: 13%, Adrenaline: 7% (OR 0.5, p=0.006) | ||||
| Favourable neurological outcome (CPC 1-2) | No adrenaline: 11%, Adrenaline 5% (OR 0.4, p=0.001) | ||||
| Survival at 1 year | No adrenaline: 12%, Adrenaline: 6% (OR 0.5, p=0.004) | ||||
| Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest. Ong ME, Tan EH, Ng FS et al. 2007 Singapore | 1296 OHCA. Two phase study. Phase I [pre-adrenaline: paramedics untrained to use adrenaline pre-hospitably (615 patients). Phase II [adrenaline phase]: Paramedics trained to use adrenaline pre-hospitably (of 681 patients 301 receive adrenaline). | Prospective observational cohort study | Survival to hospital discharge (>30 days post arrest) | Pre-adrenaline: 1%, Adrenaline: 1.6% (OR 1.7, 95% CI 0.6-4.5) [Adjusted for rhythm: OR 2.0, 95% CI 0.7-5.5] | Not a randomised placebo controlled RCT. Low rate of successful IV drug delivery. Variation in post-resuscitation care and quality of EMS care, paramedics inexperienced in endotracheal intubation and cannulation (and thus adrenaline administration). Only studied single dose adrenaline. |
| CPC 1-2 at discharge | Pre-adrenaline: 80% (n=4), Adrenaline: 81.8% (n=9) | ||||
| Who survives from out-of-hospital pulseless electrical activity? Väyrynen T, Kuisma M, Määttä T, et al. 2007 Finland | 984 OHCA with initial rhythm being pulseless electrical activity (PEA) | Retrospective observational cohort study | Short term survival rate (hospital admission alive) | No adrenaline: 62.8%, Adrenaline: 28.2% (OR 0.23, p<0.0001) | Only focused on PEA arrests. Range of other factors studied not purely adrenaline. No information on neurological outcome. No randomisation. Difficult to apply results to all EMS systems as protocols vary. |
| Long term survival rate (>30 days post arrest) | No adrenaline: 20.9%, Adrenaline: 5.5% (OR 0.22, p<0.0001) |
Author Commentary:
Adrenaline has long been used following cardiac arrest; however, data from both observational studies and randomised clinical trials (RCT) suggest its use is not beneficial, and more worryingly, may be associated with reduced long-term survival. Its ‘de facto’ use in CPR is contrary to the available evidence. A Cochrane Review is planned, the results of which could influence current guidelines; however, most beneficial would be a well-designed, multicentre placebo controlled RCT to determine if adrenaline is beneficial or harmful in the treatment of cardiac arrest.
Bottom Line:
The evidence is strong for improved short-term survival when adrenaline is administered during CPR (ROSC and/or survival to hospital admission), but may be associated with worse long-term survival and neurological outcome.
References:
- Hagihara A, Hasegawa M, Abe T.. Prehospital epinephrine use and survival among patients with out-of-hospital cardiac arrest.
- Herlitz J, Ekström L, Wennerblom B.. Adrenaline in out-of-hospital ventricular fibrillation. Does it make any difference?
- Holmberg M, Holmberg S, Herlitz J.. Low chance of survival among patients requiring adrenaline (epinephrine) or intubation after out-of-hospital cardiac arrest in Sweden.
- Jacobs IG, Finn JC, Jelinek GA, et al.. Effect of adrenaline on survival in out-of-hospital cardiac arrest: A randomised double-blind placebo-controlled trial.
- Olasveengen TM, Wik L, Sunde K, et al. . Outcome when adrenaline (epinephrine) was actually given vs. not given - post hoc analysis of a randomized clinical trial.
- Ong ME, Tan EH, Ng FS et al. . Survival outcomes with the introduction of intravenous epinephrine in the management of out-of-hospital cardiac arrest.
- Väyrynen T, Kuisma M, Määttä T, et al. . Who survives from out-of-hospital pulseless electrical activity?