1. Vasopressin versus noradrenaline infusion in patients with septic shock The New England Journal of Medicine Russel JA, Walley KR, Singer J et.al. 2008;358:877-887

2. Hypothesis: Low-dose vasopressin as compared with noradrenaline would decrease mortality amongst patients with septic shock being treated with conventional vasopressors. Secondary hypothesis: The beneficial effects of vasopressin would be more pronounced than those of noradrenaline in the subgroup of patients with more severe septic shock

3. Design ● Multicentre ● Randomized ● Double blind ● Strict protocol ● Adequately powered ● Primary endpoint – Mortality at day 28

4. Design ● Multicentre ● Randomized ● Double blind ● Strict protocol ● Adequately powered ● Primary endpoint – Mortality at day 28

5. Design ● Multicentre ● Randomized ● Double blind ● Strict protocol ● Adequately powered ● Primary endpoint – Mortality at day 28

6. Enrolement ● 6229 assessed ● 5427 excluded ● N = 778 – 396 vasopressin – 382 noradrenaline

8. Baseline characteristics

11. Results ● No significant difference in 28 day mortality between vasopressin and noradrenaline groups (35.4% v 39.3%) P=0.26 ● No SD in 90 day mortality (43.9% v 49.6%) P=0.11 ● No SD in serious adverse events (10.3% v 10.5%) P=1.00

12. Results ● Stratifying according to sepsis severity: ● Less severe shock 28-day mortality in vasopressin group 26.5% v 35.7% P=0.05. 90 day mortaility not discussed ● No difference in more severe sepsis group at 28 days (44% v 42.5%) P=0.76

13. Adverse events

14. Impression ● Well designed study – Randomized – Double blind – Power analysis ● Clear, predefined endpoints ● Exclusions well presented ● Long time period ● Error in mortality estimate

15. Conclusion ● This is ICU ● Vasopressin is expensive, shiny and new. ● It must be fantastic ● Well, for a year or two, anyway ! (N.B. This conclusion may not be entirely accurate)