Eligibility for drotrecogin alfa therapy on the basis of APACHE II score and organ failure

Introduction

Drotrecogin alfa was licensed for severe sepsis in Europe in patients with >1 organ failure (OF); in contrast to the USA where it is licensed on the basis of APACHE II score > 24. At our institution, the drug and therapeutics committee (despite ICU representation) insisted that the drug should be reserved for patients with an APACHE II score > 24 and >1 OF. Following 1 year of use, there was a concern that only one patient received the drug. To investigate the reason for this, we conducted this study to establish what proportion of patients fitted our criteria and whether suitable patients were missed.

Aims

To assess patients with APACHE II score > 24 for their suitability for drotrecogin alfa therapy. To establish whether patients met the inclusion criteria and exclusion criteria. Additionally, to follow the outcome of those who were suitable for the drug.

Method

Using the GE Medical Systems QS Clinical Information System, the last 50 patients with APACHE II score > 24 were identified from 23 March 2004 to 1 June 2004 (70 days). They were retrospectively assessed to identify whether they met the organ failure criteria from the Prowess study [1] and the SIRS criteria [1]. Patients were deemed unsuitable if they did not have a realistic chance of recovery on admission. This was reviewed by the ICU pharmacist and clinical director. Infection was regarded as those being treated with an antibiotic within the first 48 hours (microbiologists advised on all antibiotic prescribing).

Results

During the monitoring period, 222 ICU patients were admitted. Of the 50 patients with APACHE II score > 24, 46% met the SIRS criteria, 54% had >1 OF and 58% had signs of an infection. Seventy per cent of patients had contraindications to drotrecogin alfa use, the most common being active internal bleeding, recent major surgery and GI bleeding within 6 weeks (12% each). Only one patient (0.45% of admissions) met all the suitability criteria. This same patient was the only case where the drug was used; the patient initially rallied but died 7 days later.

Conclusion

The single patient who fitted the criteria received the drug, but did not survive. For severely septic patients, using the criteria of APACHE II score > 24 and >1 OF for suitability of treatment with drotrecogin alfa resulted in an extremely low proportion of patients who were eligible for therapy. These criteria should be reviewed so a wider population may benefit from this drug.