Comparison Between Continuous and Intermittent Administration of Hydrocortisone During Septic Shock: A Randomized Controlled Clinical Trial

Tilouche, Nejla; Jaoued, Oussama; Gharbi, R.; Hassen, M. Fekih; Elatrous, Souheil

doi:10.1097/shk.0000000000001316

Cited by 19 publications

(8 citation statements)

References 17 publications

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“…If we use continuous infusion in compliance with the guidelines, the total dose of hydrocortisone administered in the first hour is less than 10 mg, which is an absolutely small dose of steroid in life-threatening, rapidly deteriorating septic shock. In line with this, the intermittent administration of hydrocortisone was better in shock reversal than continuous infusion in a recent clinical study [36]. In this respect, a bolus injection of steroids could be considered.…”

Section: Discussionmentioning

confidence: 78%

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model

Park

Lee

Bae

et al. 2022

Life

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Steroids are currently being used in sepsis, particularly in septic shock. However, clinical trials to date have shown contradictory results. This could be attributed to the different patient endotypes and steroid doses, which have also contributed to the inconclusive results. We investigated the effects of glucocorticoid therapy on sepsis in a polymicrobial sepsis model in a variety of settings, such as steroid dose, severity, and sepsis phase. We used a rat model of fecal slurry polymicrobial sepsis. First, we investigated the optimum dose of steroids in a sepsis model. We administered different doses of dexamethasone after sepsis induction (0.1DEX; 0.1 mg/kg, 0.2DEX; 0.2 mg/kg, 5DEX; 5 mg/kg). Second, we used two different severities of the fecal slurry polymicrobial sepsis rat model to examine the effects of the steroids. A moderate or severe model was defined as a survival rate of approximately 70% and 30%, respectively. Third, we administered steroids in an early (1 h after sepsis induction) or late phase (25 h after sepsis). In all the experiments, we investigated the survival rates. In the determined optimal model and settings, we measured serum lactate, alanine transferase (ALT), creatinine, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-10, and arterial blood gas. We evaluated the bacterial burden in the blood and spleen. Endotoxin tolerance of peripheral blood mononuclear cells (PBMCs) and splenocytes was also investigated to determine the level of immune suppression 24 h after sepsis by measuring TNF-α production after stimulation with lipopolysaccharide (LPS) in an ex vivo model. Early treatment of 0.2 mg/kg dexamethasone in a severe sepsis model showed the best beneficial effects. In moderate- or late-phase sepsis, there was no survival gain with steroid treatment. DEX 0.2 group showed less acute kidney injury manifested by serum creatinine and blood urea nitrogen. DEX decreased the levels of cytokines, including IL-6, IL-10, and TNF-α. Colony-forming units were significantly decreased in the blood when administered with dexamethasone. Endotoxin tolerance was not significantly different between the DEX 0.2 and control groups. In conclusion, early treatment of 0.2 mg/kg dexamethasone improved the outcomes of rats in a severe sepsis model.

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Section: Discussionmentioning

confidence: 78%

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model

Park

Lee

Bae

et al. 2022

Life

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“…A recent RCT was conducted on 29 patients by Tilouche et al ., and they found no significant difference between intermittent bolus and continuous infusion; however, the sample size was small, and hyperglycemia was not the primary outcome. [ 17 ] Gibbison et al . conducted a meta-analysis among different regimens of steroids in septic shock patients including hydrocortisone intermittent bolus and continuous infusion; however, they did not find the difference in hyperglycemia between different regimens due to significant variation in defining hyperglycemia between trials.…”

Section: Discussionmentioning

confidence: 99%

“…[ 13 14 15 ] Tilouche et al . found that hydrocortisone boluses ideal for the faster reversal of shock than continuous infusion,[ 17 ] but their study showed no significant difference in the times until shock reversal between the two groups. Although they did discover a trend toward decreased vasopressor duration in the bolus group by a median of 0.6 days, it was not statistically significant.…”

Section: Discussionmentioning

confidence: 99%

Hyperglycemia Risk Evaluation of Hydrocortisone Intermittent Boluses versus Continuous Infusion in Septic Shock

Ram

Shekhar

Singh

et al. 2022

Anesthesia Essays &Amp; Researches

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Background: Hydrocortisone showed an important role in reversal of shock when added to standard therapy in managing septic shock. Hyperglycemia is one of the most common side effects associated with corticosteroid treatment. Aims: This study aimed to evaluate the risk of hyperglycemia of intermittent hydrocortisone boluses versus continuous infusion in septic shock patients. Settings and Design: This was a prospective randomized controlled study conducted in a tertiary care teaching hospital. Materials and Methods: One hundred and forty patients with septic shock and who received noradrenaline were enrolled in this randomized study. Group 1 was intermittent bolus hydrocortisone group ( n = 70) and Group 2 was continuous infusion group ( n = 70). All patients who were admitted with septic shock and who received noradrenaline and hydrocortisone were included in the study. Those patients who had exceeded 200 mg per day of hydrocortisone were excluded from the study. The primary outcome of the study was mean blood glucose. Statistical Analysis Used: Qualitative variables were compared between the two groups with the Chi-square of the Fisher's exact test and continuous variables were compared using the Student's t -test or the Wilcoxon rank-sum test. Results: Out of 112 patients, 54 patients received hydrocortisone as intermittent boluses (48.2%), and 58 patients (51.8%) received continuous infusion. For the primary outcome, no statistically or clinically significant difference was found in the blood glucose estimated marginal mean: 154.44 mg.dL −1 (95% confidence interval [CI]: 144.18–166.88) in the bolus group and 160.2 mg.dL −1 (95% CI: 143.82–176.76) in the infusion group with a mean difference of 05.76 mg.dL −1 (95% CI: −13.86–25.38). For the secondary outcomes of the study, no difference was found between the two groups in hyperglycemic or hypoglycemic events, mortality, length of stay in intensive care unit, and reversal of shock. Conclusions: The risk of hyperglycemia is almost equal in both intermittent and continuous infusions of hydrocortisone in septic shock patients.

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“…Two studies assessed whether intermittent vs. continuous administration of hydrocortisone, a corticosteroid, improved reversal of shock in ICU patients. A retrospective study did not show a difference in shock reversal with intermittent vs. continuous administration of hydrocortisone (53), but a small randomized open-label trial showed that intermittent administration of hydrocortisone was associated with improved shock reversal compared to continuous infusion (54). Although it is likely that these protocols affected circadian rhythmicity, this was not measured in either of these studies.…”

Section: Circadian Rhythm Restoration To Improve Outcomementioning

confidence: 99%

Circadian Disruption in Critical Illness

et al. 2020

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Circadian rhythms play a vital role in metabolic, hormonal, and immunologic function and are often disrupted in patients in the ICU. Circadian rhythms modulate the molecular machinery that responds to injury and illness which can impact recovery. Potential factors contributing to the alteration in circadian rhythmicity in intensive care unit (ICU) patients include abnormal lighting, noise, altered feeding schedules, extensive patient care interactions and medications. These alterations in circadian rhythms in ICU patients may affect outcomes and therefore, normalization of circadian rhythmicity in critically ill patients may be an important part of ICU care.

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Comparison Between Continuous and Intermittent Administration of Hydrocortisone During Septic Shock: A Randomized Controlled Clinical Trial

Cited by 19 publications

References 17 publications

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model

Effects of Glucocorticoid Therapy on Sepsis Depend Both on the Dose of Steroids and on the Severity and Phase of the Animal Sepsis Model

Hyperglycemia Risk Evaluation of Hydrocortisone Intermittent Boluses versus Continuous Infusion in Septic Shock

Circadian Disruption in Critical Illness

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