Activated protein C in severe sepsis: Single institutional experience

SUMMARY ACTIVATED PROTEIN C IN SEVERE SEPSIS: SINGLE INSTITUTIONAL EXPERIENCE Doğanay, H. Levent Department of Internal Medicine, School of Medicine, Dokuz Eylül University İzmir Address for correspondence: DEUTF Ic Hastaliklari A.D Inciralti / Izmir 35340 E-mail: levent.doganay@deu.edu.tr Aim: The mortality rate from severe sepsis remains high despite new techniques and novel treatment modalities in medicine. The number of patients diagnosed sepsis and severe sepsis is getting higher every year and sepsis becomes one of the leading causes of death. Almost half of the patients in intensive care units have severe sepsis. The results of a multinational multi-centric randomized double blinded study indicates that Activated Protein C (APC) is effective for decreasing mortality in severe sepsis patients when added to best care. And this novel drug is recommended in the sepsis guidelines. To our knowledge and according to our Medline search there is no study from Turkey reporting results of this novel therapy. In our University Hospital medical intensive care unit, APC is in use since 2003. Our aim is to assess factors affected mortality and morbidity in our group of patients. Method: Patients, who received APC in between August 2003 and April 2006 in the Medical Intensive Care Unit in Dokuz Eylül University Hospital, were included in this study. The medical records of the patients and the electronic database in intensive care unit were reviewed retrospectively. Factors affecting death on 28 day and complications were evaluated. Results: Fifty-four patients received APC during the period. Median number of organ dysfunction was four. Pneumonia was the most frequent source of infection (70.5%) causing severe sepsis. Ninety-two percent of the patients were mechanically ventilated and 88.8% of them were on vasopressor drugs, 75% of them had acute renal failure on presentation. The mortality rate on 28th day was 66.7%. The mortality was not significantly affected by age or gender. Having malignancy, intensive care acquired infection, acute renal failure or bleedingdid not significantly affect mortality, either. The patients who did not survive on day 28, needed more number of vasopressor drugs (p=0.012) during their stay and they excreted less amount of urine (p=0.025) after the beginning of drug infusion. The patients who completed 96 hour infusion period had lower mortality rate on day 28 (p=0.042). Twenty-four patients (44.4%) completed 96 hour drug infusion and 50% percent of them survived beyond 28th day. In this group, patients who did not survive had higher SOFA scores (p=0.006) and higher serum creatinine levels (p=0.033) at the end of the treatment and needed vasopressors for a longer period (p=0.008). The patients who did not survive had higher rate of ICU acquired infections (p=0.025). Eleven percent of the patients had severe bleeding. The patients who had any bleeding event had lower platelet counts (p-0.027) and higher serum creatinine levels (p=:0.028) compared to that of the non-bleeding patients. Conclusion: The patients with multiple organ failure and at very high risk of mortality received APC in our institution. Bleeding risk was higher in this group compared to those reported in the literature. It should be noted that appropriate antimicrobial treatment and appropriate fluid resuscitation at the onset of severe sepsis are important determinants of mortality in the intensive care unit. It is possible that there is a group of patients who is resistant to beneficial effects of APC. Further trials should be planned to figure out this possibility. A better prediction of who gains the most benefit with APC treatment may then become achievable. Keywords: Activated Protein C, Drotrecogin alfa, Xigris, Severe sepsis.