Risk/benefit analysis of activated protein C in patients with intra-abdominal sepsis

Introduction and objective

To establish whether activated protein C (APC) is safe in surgical patients with intra-abdominal sepsis (IAS). APC has been used in the treatment of IAS in our hospital since 2003. Fears persist regarding the potential for clinically significant bleeding in this surgical subgroup of patients.

Methods

Forty-four patients with IAS received APC as a standardized regime between March 2003 and August 2006. A retrospective medical and ICU chart review was undertaken. Data collected included clinically significant bleeding episodes and mortality. Descriptive subgroup analysis of unexpected non-survivors(died in the ICU with APACHE II (APII) predicted mortality < 50%) and unexpected survivors (survived to ICU discharge with APII predicted mortality > 50%) was performed as statistical analysis of such small patient numbers was inappropriate.

Results

There was one episode of clinically significant bleeding (from a mucous fistula: self-limiting). There were no intracranial haemorrhagic events. ICU mortality was 38.6% with mean APII predicted mortality of 37.16% and inhospital mortality of 47.7%. These exceeded rates for APC-treated surgical cohorts in the literature [1]. Unexpected survivors (5/44) were more likely to have been admitted from theatre. They had a shorter mean time from hospital–ICU admission (10.5 vs 5.6 days), duration on a ventilator (10.8 vs 17.5 days), vasopressor (9 vs 17.7 days) and renal replacement therapy (10.5 vs 23.5 days) dependence. All unexpected nonsurvivors (11/44) had a diagnosis of fistula or perforation. They were more likely to have been transferred to the ICU from another hospital or ward than from theatre. Co-morbidities were more severe.

Conclusion

1. APC was very safe to use in this group of critically ill surgical patients. 2. Although patients may fulfil standard criteria for APC use, if there is no definitive surgical cure for the IAS, then APC is inappropriate. 3. Delay in commencement of APC in surgical patients due to bleeding concerns may be contributing to the high mortality. Earlier perioperative use of APC in selected cases may offer improved mortality benefit, and we are undertaking a prospective audit to investigate this.