title: Timing, method and discontinuation of hydrocortisone administration for septic shock patients.
abstract: OBJECTIVE
  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)vs108 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%vs63%;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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Ibarra-Estrada
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Quetzalcóatl
authors.initials: Q
authors.lastname: Chávez-Peña
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Claudia I
authors.initials: CI
authors.lastname: Reynoso-Estrella
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Jorge
authors.initials: J
authors.lastname: Rios-Zermeño
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Pável E
authors.initials: PE
authors.lastname: Aguilera-González
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: García-Soto
authors.affiliation: Miguel A Ibarra-Estrada, Pável E Aguilera-González, Critical Care Unit, Instituto Jalisciense de Cancerología, Guadalajara Jalisco 44280, Mexico.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Aguirre-Avalos
keywords: Administration; Corticosteroids; Discontinuation; Hydrocortisone; Septic shock; Timing