Observational Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Feb 4, 2017; 6(1): 65-73
Published online Feb 4, 2017. doi: 10.5492/wjccm.v6.i1.65
Timing, method and discontinuation of hydrocortisone administration for septic shock patients
Miguel A Ibarra-Estrada, Quetzalcóatl Chávez-Peña, Claudia I Reynoso-Estrella, Jorge Rios-Zermeño, Pável E Aguilera-González, Miguel A García-Soto, Guadalupe Aguirre-Avalos
Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico
Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Hospital General Regional #180, Instituto Mexicano del Seguro Social, Tlajomulco de Zúñiga Jalisco 45655, Mexico
Quetzalcóatl Chávez-Peña, Miguel A García-Soto, Transplant Care Unit, Centro Médico Nacional de Occidente, Instituto Mexicano del Seguro Social, Guadalajara Jalisco 44340, Mexico
Quetzalcóatl Chávez-Peña, Guadalupe Aguirre-Avalos, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara Jalisco 44340, Mexico
Claudia I Reynoso-Estrella, Jorge Rios-Zermeño, Guadalupe Aguirre-Avalos, Critical Care Unit, Hospital Civil Fray Antonio Alcalde, Guadalajara Jalisco 44280, Mexico
Author contributions: Ibarra-Estrada MA designed the study, performed data collection, statistical analysis, interpretation of data, and drafted the manuscript; Chávez-Peña Q and Reynoso-Estrella CI performed data collection and helped draft the manuscript; Rios-Zermeño J, Aguilera-González PE, García-Soto MA and Aguirre-Avalos G performed data collection; all authors were involved and approved the final manuscript.
Institutional review board statement: This study has been approved by the scientific and ethics committees at Instituto Jalisciense de Cancerología (INV-01/16), and Hospital Civil Fray Antonio Alcalde (HCG/CEI-0321/16). A copy of approval can be provided on request.
Informed consent statement: All study participants, or their next of kin, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: None of the authors have commercial associations or financial involvements that might pose a conflict of interest related to the content of this article.
Data sharing statement: Data presented in the manuscript is anonymized, and the risk of identifying individual patients is very low. No additional data is available from the study other than the data stated in this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Miguel A Ibarra-Estrada, Critical Care Unit, Instituto Jalisciense de Cancerología, Coronel Calderón 715, Guadalajara Jalisco 44280, Mexico. drmiguelibarra@hotmail.com
Telephone: +52-33-40401508
Received: August 24, 2016
Peer-review started: August 25, 2016
First decision: October 20, 2016
Revised: November 6, 2016
Accepted: January 11, 2017
Article in press: January 14, 2017
Published online: February 4, 2017
Processing time: 151 Days and 4.4 Hours
Abstract
AIM

To characterize the prescribing patterns for hydrocortisone for patients with septic shock and perform an exploratory analysis in order to identify the variables associated with better outcomes.

METHODS

This prospective cohort study included 59 patients with septic shock who received stress-dose hydrocortisone. It was performed at 2 critical care units in academic hospitals from June 1st, 2015, to July 31st, 2016. Demographic data, comorbidities, medical management details, adverse effects related to corticosteroids, and outcomes were collected after the critical care physician indicated initiation of hydrocortisone. Univariate comparison between continuous and bolus administration of hydrocortisone was performed, including multivariate analysis, as well as Kaplan-Meier analysis to compare the proportion of shock reversal at 7 d after presentation. Receiver operating characteristic (ROC) curves determined the best cut-off criteria for initiation of hydrocortisone associated with the highest probability of shock reversal. We addressed the effects of the taper strategy for discontinuation of hydrocortisone, noting risk of shock relapse and adverse effects.

RESULTS

All-cause 30-d mortality was 42%. Hydrocortisone was administered as a continuous infusion in 54.2% of patients; time to reversal of shock was 49 h longer in patients who were given a bolus administration [59 h (range, 47.5-90.5) vs 108 h (range, 63.2-189); P = 0.001]. The maximal dose of norepinephrine after initiation of hydrocortisone was lower in patients on continuous infusion [0.19 μg/kg per minute (range, 0.11-0.28 μg)] compared with patients who were given bolus [0.34 μg/kg per minute (range, 0.16-0.49); P = 0.004]. Kaplan-Meier analysis revealed a higher proportion of shock reversal at 7 d in patients with continuous infusion compared to those given bolus (83% vs 63%; P = 0.004). There was a good correlation between time to initiation of hydrocortisone and time to reversal of shock (r = 0.80; P < 0.0001); ROC curve analysis revealed that the best criteria for prediction of shock reversal was a time to initiation of hydrocortisone of ≤ 13 h after administration of norepinephrine, with an area under the curve of 0.81 (P < 0.001). The maximal dose of norepinephrine at initiation of hydrocortisone with the highest association with shock reversal was ≤ 0.28 μg/kg per minute, with an area under the curve of 0.75 (P = 0.0002). On a logistic regression model, hydrocortisone taper was not associated with a lower risk of shock relapse (RR = 1.29; P = 0.17) but was related to a higher probability of hyperglycemia [odds ratio (OR), 5.3; P = 0.04] and hypokalemia (OR = 10.6; P = 0.01).

CONCLUSION

Continuous infusion of hydrocortisone could hasten the resolution of septic shock compared to bolus administration. Earlier initiation corresponds with a higher probability of shock reversal. Tapering strategy is unnecessary.

Keywords: Corticosteroids; Hydrocortisone; Timing; Administration; Discontinuation; Septic shock

Core tip: Until now, the indications, timing, administration, and discontinuation of hydrocortisone for septic shock patients have been widely variable. Our study found that continuous infusion was the most effective method compared to bolus administration; we also identified a time from vasopressor administration of ≤ 13 h and/or a norepinephrine dose of ≤ 0.28 μg/kg per minute as the best clinical criteria for initiation of hydrocortisone. We found no benefit from the tapering strategy, which was only associated with a higher incidence of hyperglycemia and hypokalemia.