Low-dose and high-dose corticotropin stimulation test in septic shock patients

Introduction

Septic shock is frequently associated with relative adrenal insufficiency (RAI). RAI increases mortality and hydrocortisone supplementation improves survival in septic shock patients. There is no consensus about RAI diagnosis criteria. With the standard corticotropin stimulation test (SCST) (250 μg) ACTH levels reaches 100 times the physiological concentration. A low-dose corticotropin stimulation test (LDCST) (1 μg) is closer to physiological ACTH levels.

Objective

To determine whether a LDCST (1 μg) can reveal RAI in septic shock patients when the SCST (250 μg) does not diagnose RAI.

Methods

A prospective cohort study conducted between October 2003 and May 2004 in an adult intensive care unit of a teaching hospital in France. A baseline cortisol concentration was obtained in septic shock patients. An intravenous injection of 1 μg corticotropin (LDCST) followed 90 min later by an injection of 249 μg corticotropin (SCST) was performed. Cortisol concentrations were obtained 30 and 60 min after each test. All patients received hydrocortisone (50 mg/6 hours intravenous bolus) and fludrocortisone (50 μg tablet once daily) while awaiting the results of cortisol assesment. Patients were considered without RAI if Delta max > 9 mg/dl. Delta max is defined as the difference between T0 and the highest value between T30 and T60 of each test. Hydrocortisone and fludrocortisone were delivered for 7 days if the patient had RAI on SCST and stopped in the other cases.

Results

Twenty-three patients with septic shock were enrolled. Their mean age was 60 ± 14 years; 16 were male. IGS II was 52 ± 21 and the SOFA score at admission was 9 ± 3. Sixteen patients (63%) were admitted for nosocomial infection, 14 (61%) for peritonitis, six (26%) for pulmonary infection and three for other sites of infection. Seven patients died at day 28 (33%) and nine in the intensive care unit (40%). Baseline cortisol levels were 12.69 ± 7.24 μg/dl. Twenty-one patients met the diagnosis criteria of RAI with the LDCST and 18 with the SCST (Delta max LDCST: 10.78 ± 1.37; Delta max SCST: 17.44 ± 4.53). Three patients had RAI with the LDCST but not with the SCST.

Conclusion

The incidence of RAI was very high in our study population with the SCST (78%). We found three patients without RAI according to the SCST but showing impaired response to the LDCST. The small number of patients in this situation does not allow any conclusion about the best test to choose. It seems of interest to enlarge our cohort of patients to draw clinically relevant information.