Therapy A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation
This review may be edited
Summary
Posted By:	todd fraser
E-Mail:	lil_frog@bigpond.net.au
Posted Date:	13/1/4
Title:	A comparison of vasopressin and epinephrine for out-of-hospital cardiopulmonary resuscitation
Authors:	Wenzel V, Krismer A, Arntz R et al
Reference:	NEJM 2004; 350:105-13
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	Background Vasopressin is an alternative to epinephrine for vasopressor therapy during cardiopulmonary resuscitation, but clinical experience with this treatment has been limited. Methods We randomly assigned adults who had had an out-of-hospital cardiac arrest to receive two injections of either 40 IU of vasopressin or 1 mg of epinephrine, followed by additional treatment with epinephrine if needed. The primary end point was survival to hospital admission, and the secondary end point was survival to hospital discharge. Results A total of 1219 patients underwent randomization; 33 were excluded because of missing study-drug codes. Among the remaining 1186 patients, 589 were assigned to receive vasopressin and 597 to receive epinephrine. The two treatment groups had similar clinical profiles. There were no significant differences in the rates of hospital admission between the vasopressin group and the epinephrine group either among patients with ventricular fibrillation (46.2 percent vs. 43.0 percent, P=0.48) or among those with pulseless electrical activity (33.7 percent vs. 30.5 percent, P=0.65). Among patients with asystole, however, vasopressin use was associated with significantly higher rates of hospital admission (29.0 percent, vs. 20.3 percent in the epinephrine group; P=0.02) and hospital discharge (4.7 percent vs. 1.5 percent, P=0.04). Among 732 patients in whom spontaneous circulation was not restored with the two injections of the study drug, additional treatment with epinephrine resulted in significant improvement in the rates of survival to hospital admission and hospital discharge in the vasopressin group, but not in the epinephrine group (hospital admission rate, 25.7 percent vs. 16.4 percent; P=0.002; hospital discharge rate, 6.2 percent vs. 1.7 percent; P=0.002). Cerebral performance was similar in the two groups. Conclusions The effects of vasopressin were similar to those of epinephrine in the management of ventricular fibrillation and pulseless electrical activity, but vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in the treatment of refractory cardiac arrest.
Are the Results Valid?
1. Was the assignment of patients to treatments randomized?
	Yes. "Treatment assignments to the study drugs were randomly generated in blocks of 10, with stratification according to center. If all criteria for inclusion were met and none of the criteria for exclusion were met, patients who presented with pulseless electrical activity or asystole underwent randomization immediately; patients with ventricular fibrillation underwent randomization after the first three attempts at defibrillation had failed."
2. Were all patients who entered the trial properly accounted for and attributed at its conclusion?
2a. Was followup complete?
	Yes. 33 patients were lost from the study due to drug code loss. Though no details are given the authors state that the characteristics of these 33 patients were no different to the others. It is unlikely to have affected the results.
2b. Were patients analyzed in the groups to which they were randomized?
	All patients were analysed on an intention to treat basis. This included 80 patients who were unintentionally included in the study dispite meeting exclusion criteria.
3. Were patients, health workers, and study personnel blind to treatment?
	Yes, though details are lacking
4. Were the groups similar at the start of the trial?
	Yes.
5. Aside from the experimental intervention, were the groups treated equally?
	It appears so.
What are the Results?
1. How large was the treatment effect?
	Overall, there was no difference in either hospital admission rate or hospital discharge rate. Additionally, no placebo arm was included, and adrenaline has not been proven to improve outcome in cardiac arrest.<>br On subgroup analysis, there was a statistically significant increase in admission and discharge rates of those patients in whom the presenting rhythm was asystole. Those asystolic patients who recieved vasopressin were 3 times more likely to leave hospital than those who recieved adrenaline. Of those who were refractory to the study drug and recieved ongoing adrenaline (as per trial protocol), those who recieved vasopressin were 3 times more likely to survive to discharge. This applied to all patients, but only to asystole on subgroup analysis.
2. How precise was the estimate of the treatment effect?
	Confidence intervals for the odds ratio hospital admission and discharge for asystolic patients were included. For survival to discharge from hospital after vasopressin therapy was 0.3 (0.1-1.0), which includes the possibility of no significant difference (p value was reported at 0.04).
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care?
	The study was conducted in multiple centres in westernised countries. The protocol for resuscitation appeared consistent with international standards, including those used in Australia.
2. Were all clinically important outcomes considered?
	The primary endpoint was hospital admission, with hospital discharge the secondary endpoint.<>br> Only 57/589 patients in the vasopressin group and 58/588 patients in the adrenaline group survived to discharge. Neurological outcome is not available on all patients. However, on a four point scale of good outcome, moderate, severe or total impairment, there was no significant difference in outcome. This data would be important in assessing the clinical value of the intervention. Cost effectiveness of the trial protocol would similarly be important, and would include both the cost of care for survivors in hospital and long term care for neurologically impaired survivors.
3. Are the likely treatment benefits worth the potential harms and costs?
	Unclear from the results of this study. Further trials would be required to validate results, and to assess neurological outcome at discharge.
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