VSE

VSE: Vasopressin, Steroids and Epinephrine and Neurologically Favourable Survival After In-Hospital Cardiac Arrest A Randomized Clinical Trial

Mentzelopoulos. JAMA.2013;310(3):270-279. doi:10.1001/jama.2013.7832

In patients in cardiac arrest, does vasopressin + epinephrine during CPR combined with steroid supplementation during and after CPR, improve survival to discharge with a good neurological outcome, in comparison to the use of epinephrine alone?

Randomized, double-blind, placebo-controlled, parallel-group trial
- blinding of staff assessing neurological outcome
Block randomisation stratified by centre
Modified intention to treat
- randomised patients who did not require vasopressors were excluded
- randomised patients that survived but who did not have post-resuscitation shock were excluded from subgroup analysis
Based on a predicted survival with favourable neurological recovery of 15% in the intervention group and 4% in the control group, the study was powered at 80%, with alpha set at 0.05, if 244 patients enrolled.
Multi-variance logistic regressions used to determine Odds Ratios (OR)

Inclusion: in-hospital vasopressor-requiring cardiac arrest
- Location of cardiac arrest: 16% ED, 41% ICU/CCU/Operating room, 43% hospital ward
Exclusion: age<18, terminal illness/DNAR, cardiac arrest due to exsanguination, pre-hospital cardiac arrest, treatment with IV steroids prior to arrest
300 randomised out of 364 assessed for eligibility
- 32 patients excluded post-randomisation as ROSC prior to need for vasopressors
- Comparing intervention vs. control group, similar baseline characteristics apart from:
  - male sex 73.1% vs. 63.8%
  - hospital stay before arrest (median) 5 days vs 2 days
  - cause of cardiac arrest
    - metabolic 8.5% vs 15.2%
    - hypotension 46.9% vs. 37%
    - myocardial ischaemia/infarction 23.1% vs. 17.4%
  - Initial rhythm
    - asytole 63.8% vs. 70.3%, P=0.3
    - PEA 19.2% vs. 13%, P=0.19
- No significant differences in use of primary PCI or therapeutic hypothermia between study groups

Average CPR cycle duration ~3min in both intervention and control groups

Primary outcome:
- survival to hospital discharge with favourable neurological outcome (Glasgow-Pittsburgh Cerebral Performance Category 1/2)
  - significant improvement in intervention group
    - 13.9% vs. 5.1%; (OR 3.28, 95% C.I. 1.17-9.2, P=0.02, NNT 12)
Secondary outcome:
- ROSC for >20 minutes (stated as a 2nd primary outcome, but power calculation not performed for this outcome)
  - significant improvement in intervention group
    - 83.9% vs. 65.9%, (OR 2.98 95% C.I. 1.39-6.4, P=0.005, NNT 6)
- Patients with post-resuscitation shock had significant improvement of survival to discharge with a good neurological outcome in the intervention group vs. control group
  - 21.1% vs 8.2%, OR 3.74 (95% C.I. 1.2-11.62, P=0.02)
- Number of patients receiving insulin treatment within 1st 10 days – significantly higher in intervention group
  - 50.4% vs. 36%, P<0.001
- There was no significant difference in rates of infection or gastro-intestinal bleeding between the two groups

Patient in cardiac arrest requiring vasopressors, have an improved survival with a good neurological outcome if they are treated with combined vasopressin/epinephrine/steroids compared with epinephrine alone

Single geographical area
Small number of patients in total survived with a good neurological outcome (25 in total) making it difficult to make any definite decisions
Therapeutic hypothermia only used in 24.6% of patients
Atropine and bicarbonate used on a number of patients which is not consistent with current practice
Differences in baseline characteristics between the 2 groups
Large number of patients had cardiac arrest in critical care environment. These results may be be generalisable to centres at which this does not happen.
Bundle approach means that we do not know whether it was the whole bundle or any of the bundle elements that caused any differences in results found

This study has shown a significant improvement for survival to discharge with a good neurological outcome following cardiac arrest when treated with combination steroids/vasopessin/epinephrine in comparison to epinephrine alone. Of note, no RCT has shown this improvement when using epinephrine alone compared with placebo.
However, before introducing this into routine practice I am waiting for a validation study in a different setting. This is a single study, set in only 3 centres in 1 country. There were only 18 patients who survived with a good outcome in the intervention group. We know that a number of promising treatments have been disproven when studies have been repeated in larger trials. I hope that someone takes up the challenge of attempting to validate this trial on an urgent basis so that a more evidenced based decision can be made.

Summary author: @davidslessor
Summary date: 8 August 2014
Peer-review editor: @DuncanChambler