Age and number of organ dysfunctions are associated with early mortality in patients suffering from severe sepsis treated with recombinant human activated protein C

Introduction

It has been shown that age and number of organ dysfunctions (OD) correlate with outcome of patients suffering from severe sepsis (SS). Recently, the PROWESS study (phase III, double-blind, placebo-controlled trial) had demonstrated that recombinant human activated protein C (rhAPC) reduces the absolute risk of 28-day all-cause mortality by 6.1% in patients suffering from SS. As a result in Mexico, from August 2002 until October 2003, 206 patients have been treated with rhAPC. The present study is to identify the main variables that contribute to early mortality (first 8 days) in patients treated with rhAPC.

Methods

Data from 206 patients treated with rhAPC from 58 public and private medical institutions all over Mexico were analyzed retrospectively. Age, origin of SS, number of OD, timing of rhAPC administration, and complications during rhAPC were used as independent variables. Cross-tabulation and chi-square analysis were performed to identify those variables that contribute to mortality at 8 days of SS.

Results

Intra-abdominal sepsis was the most common origin of SS (46.6%), followed by postoperative sepsis, pneumonia and others (28.6%, 19.4% and 5.3%, respectively). There were no differences in mortality about patients treated in public hospitals compared with patients treated in private hospitals. The mean age of patients treated was 58.80 years (19–89 years). The mean of OD was 2.78 (1–6), the mean of timing administration of rhAPC was 50.94 hours (4–504 hours), and global mortality at 1 week was 31.6%. Age was associated with mortality; patients younger than 41 years had 14.7% mortality, in contrast with patients older than 65 years with 48.3% mortality (P = 0.000). The number of OD was associated with mortality; patients with one OD had 21.4% mortality in contrast with 37.7% mortality in patients with three or more OD (P = 0.040). Patients younger than 41 years with one OD had 0% mortality, two OD 11.8% and three or more OD 21.4%; patients between 40 and 65 years with one OD had 25% of mortality, two OD 20.0% and three OD 33.3%. Patients older than 65 years with one OD had 25% of mortality, two OD 50% and three or more OD 50% (P = 0.003). Bleeding was observed in 4.7% of patients, and one dead by cerebral haemorrhage associated with rhAPC (0.48%) was reported.

Conclusions

Age and the number of OD are highly associated with mortality at 1 week of SS on patients that were treated with rhAPC. Patients suffering from SS have to be treated at an early stage of sepsis.