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Critical Care

Open Access

Potential for overuse of corticosteroids and vasopressin in septic shock

  • Joe L Hsu1Email author,
  • Vincent Liu2,
  • Andrew J Patterson3,
  • Greg S Martin4,
  • Mark R Nicolls1 and
  • James A Russell5
Critical Care201216:447

Published: 6 September 2012


CorticosteroidSeptic ShockVasopressinSeptic Shock PatientVasopressor Therapy

Guidelines recommend corticosteroids and vasopressin to treat septic shock as per specific indications [1]. However, the results from trials evaluating both drugs conflict. For corticosteroids, the 2002 Annane and colleagues study showed a survival benefit for hydro-cortisone/fludrocortisone treatment in patients with an inappropriate cortisol response to a high-dose adrenocorticotropic hormone (ACTH) test [2], while the Corticosteroid Therapy of Septic Shock (CORTICUS) trial found no difference in survival by patients' response to ACTH [3]. The Vasopressin and Septic Shock Trial (VASST) demonstrated a survival benefit in less severe septic shock, but guidelines espouse use 'in patients refractory to other vasopressors' [1, 4]. Clinical variability, leading to overtreatment, may have negative effects on survival. To evaluate the impact of these evidence limitations, we surveyed physicians in the Critical Illness Outcomes Study (CIOS).

We developed a 15-item, self-administered survey to characterize physician practice patterns for use of corticosteroids and vasopressin in septic shock. The survey, conducted anonymously and with implied consent, was distributed to 92 members of the CIOS listserv. Recipients were encouraged to solicit survey completion by their colleagues. CIOS is a multicenter study among 68 ICUs designed to determine whether ICU-based organizational and structural factors are associated with patient-related outcomes. The survey fulfilled Stanford Institutional Review Board exemption guidelines. To address when clinicians would use corticosteroids, we asked participants to rate their agreement (five-point Likert scale) for the following situations: blood pressure poorly responsive to fluid resuscitation and vasopressor therapy; an inappropriate response to ACTH testing [2]; and a history of treatment with corticosteroids within the prior 6 months. Likert responses were evaluated by Pearson correlation coefficients. For vasopressin, we asked whether physicians preferentially used vasopressin in more or less severe septic shock, as defined by the VASST [4].

Per 140 completed surveys (87% from academic institutions), corticosteroids and vasopressin were used commonly in septic shock (90% and 99%, respectively). Thirty-nine percent used corticosteroids in more than one-quarter of septic shock patients (Figure 1). Eight-eight percent of respondents agreed with Surviving Sepsis guidelines for blood pressure-based corticosteroid therapy; however, fewer agreed with ACTH-based (47%) or history-based (62%) indications (Figure 2). Agreement with these indications among providers was poorly correlated: 0.38 between blood pressure and ACTH indications, and 0.13 between blood pressure and history. Eighty-seven percent used vasopressin in more severe septic shock.
Figure 1

Use of corticosteroids and vasopressin in septic shock. How frequently (percentage of patients) do you use (A) corticosteroids or (B) vasopressin in septic shock?

Figure 2

Indications for corticosteroid use in septic shock. Three scenarios were evaluated. Blood pressure: whether blood pressure is identified to be poorly responsive to fluid resuscitation and vasopressor therapy. Adrenocorticotropic hormone (ACTH): whether there is an inappropriate response to a high-dose ACTH stimulation test (change in cortisol <9 μg/dl). History: whether the patient has been treated previously with corticosteroids (within the previous 6 months). Concordance with Surviving Sepsis Guidelines: 88% for blood pressure, 47% for ACTH and 62% for history.

Substantial variability exists in use of corticosteroids and vasopressin in septic shock. Although agreement exists regarding the use of corticosteroids for refractory hypotension, other indications demonstrated poor to modest guideline concordance. Nearly one-third of respondents considered failure to respond to an ACTH test as an appropriate indication for corticosteroid use, despite negative results from the CORTICUS trial and variability of current cortisol assays [3, 5]. Overtreatment with corticosteroids could increase incidence of secondary infections [3]. Vasopressin use contradicted the conclusions from the VASST [4]. As septic shock mortality remains high, work is needed to reduce variability through research and adherence to evidence from clinical trials [24].



adrenocorticotropic hormone


Critical Illness Outcomes Study


Corticosteroid Therapy of Septic Shock


tumor necrosis factor


Vasopressin and Septic Shock Trial.



The authors thank the members of the CIOS for taking the time to complete the practice pattern survey. They would also like to acknowledge Dr Gomathi Krishnan and the Stanford University Center for Clinical Informatics for their assistance with the creation and distribution of the survey.

Authors’ Affiliations

Department of Medicine, Division of Pulmonary and Critical Care Medicine, Stanford University Hospital, Stanford University School of Medicine, Stanford, USA
Kaiser Permanente Division of Research and Systems Research Initiative, Oakland, USA
Department of Anesthesia, Stanford University Hospital, Stanford, USA
Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University School of Medicine, SE, Atlanta, USA
Critical Care Research Laboratories, Institute of Heart and Lung Health, St. Paul's Hospital, Vancouver, Canada


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© BioMed Central Ltd 2012