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Critical Care Medicine


Answer 1
  1. Drotrecogin alfa (activated). The patient clearly has sepsis as evidenced by the presence of all 4 criteria of the systemic inflammatory response syndrome: hyperthermia, leukocytosis, tachycardia, and tachypnea due to a presumed pneumococcal infection. The presence of organ dysfunction due to sepsis (renal, hepatic, respiratory, and central nervous system) as well as lactic acidosis constitute the diagnosis of severe sepsis. Furthermore, cardiovascular failure in the form of systemic hypotension further supports a diagnosis of septic shock. Recombinant human activated protein C (rhAPC), or drotrecogin alfa (activated), is the only treatment approved for reducing mortality in patients with severe sepsis and a high risk of death. Although the definition of “high risk” may vary, the case patient is clearly at a high risk of death as evidenced by his multisystem organ dysfunction, shock, and respiratory failure (APACHE II score, 30). In a large randomized, placebo-controlled trial of patients with severe sepsis (PROWESS trial),1 drotrecogin alfa (activated) administered as a continuous IV infusion at 24 µg/kg/hr for 96 hours resulted in a 19.4% relative risk reduction in 28-day mortality and a 6.1% absolute reduction in the risk of death. This survival benefit was even more pronounced in patients with more than 1 organ dysfunction or APACHE II score of 24 or greater.
    A small multicenter study suggested that low-dose IV hydrocortisone and oral fludrocortisone reduced mortality in septic shock patients with relative adrenal insufficiency, defined as a failure to increase serum cortisol levels by 9 mg/dL or more in response to adrenocorticotropin hormone (ACTH) stimulation.2 However, the case patient’s response to ACTH stimulation is unknown, and the study found no benefit in patients who responded appropriately to stimulation. A large multicenter study of a similar strategy demonstrated no survival benefit of hydrocortisone (overall or in nonresponders to ACTH stimulation) in patients with septic shock.3 The effect of IVIG in patients with severe sepsis has had varying results. A recent multicenter study found no 7-day or 28-day survival benefit with IVIG in patients with severe sepsis.4 A randomized, placebo-controlled, multicenter trial of 10% pentastarch showed no reduction in 28-day or 90-day mortality and an increased incidence of acute kidney injury (AKI) as compared with resuscitation with modified lactated Ringer’s solution.5 A large study of higher-intensity RRT in patients with AKI failed to demonstrate an improvement in any clinical outcome, including 28-day mortality, over standard RRT.6 There are no data to suggest that RRT would benefit this patient at his current stage of AKI.

    REFERENCES
    1. Bernard GR, Vincent JL, Laterre PF, et al; Recombinant human protein C Worldwide Evaluation in Severe Sepsis (PROWESS) Study Group. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001;344:699–709.

    2. Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA 2002;288:862–71.

    3. Sprung CL, Annane D, Keh D, et al; the Corticosteroid Therapy of Septic Shock (CORTICUS) Study Group. Hydrocortisone therapy for patients with septic shock. N Engl J Med 2008;358:111–24.

    4. Werdan K, Pilz G, Bujdoso O, et al; Score-Based Immunoglobulin Therapy of Sepsis (SBITS) Study Group. Score-based immunoglobulin G therapy for patients with sepsis: the SBITS study. Crit Care Med 2007;35:2693–701.

    5. Brunkhorst FM, Engel C, Bloos F, et al; German Competence Network Sepsis (SepNet). Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med 2008;358:125–39.

    6. Palevsky PM, Zhang JH, O’Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med 2008;359:7–20.

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