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Corticosteroids, lactated Ringer’s solution appropriate approaches to managing sepsis

ORLANDO, Fla. – Evidence supports the use of hydrocortisone in more severely ill patients with sepsis, according to a presentation here at Hospital Medicine 2018.

Other studies discussed showed no benefit to early, goal-directed therapy, a risk of cardiac arrest from higher positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome and increased risk of hypotension in patients who received extended targeted temperature management.

The ADRENAL study, examining hydrocortisone in 3,658 patients with septic shock, and the APROCCHSS study, combining hydrocortisone and fludrocortisone in 1,241 patients with septic shock, were published earlier this year in the New England Journal of Medicine. APROCCHSS found a statistically significant difference in mortality — 43% vs 48% in the placebo group — although no mortality benefit was identified in ADRENAL. Of potentially greater importance was that both treatment regimens reduced duration of vasopressors, quickly resolved shock, did not increase rate of infection, and reduced time in the ICU and in the hospital, according to Patricia Kritek, MD, EdM, professor in the Division of Pulmonary, Critical Care and Sleep Medicine at the University of Washington.

The patients in both trials had more severe illness, which made Kritek reluctant to issue a sweeping recommendation for the use of corticosteroids in all patients.

“I think it’s reasonable to use hydrocortisone ... in patients with refractory septic shock,” she said.

An additional study from last year that received considerable attention from the lay media combined vitamin C, for its antioxidant properties, and thiamine, for kidney protection, with hydrocortisone and showed a significant impact on mortality — 9% vs 40% in the placebo group. Kritek was quick to point out this one-center study with 94 patients has not been replicated. Although it has a low downside, and the treatment is inexpensive, she recommended that more experience in patients is needed before implementing on a wider scale.

Lactated Ringer’s solution superior to saline

The administration of balanced lactated Ringer’s solution was found to be superior to normal saline in another trial published in the New England Journal of Medicine earlier this year in the number of major adverse kidney events. This trial also comes with a caveat in that the findings were significant for the combination but not the individual elements — in hospital death, new renal replacement therapy or final creatine more than 200% of baseline, Kritek said. An additional takeaway for clinicians was that patients who received more fluid had better outcomes, she noted.

EGDT offered no benefit

A meta-analysis for three large-scale trials on the efficacy of EGDT for septic shock from the last several years confirmed the individual findings of those trials that this approach did not offer any additional benefit to patients. Combining the patient cohorts enabled researchers to perform a subanalysis of patients with more severe disease, but again, no benefit was seen, Kritek said. The meta-analysis also allowed for a review of cost-efficiency, and EGDT was found to be more expensive.

Though the findings from this trial were negative, expect additional trials to determine the best strategy for providing fluids, because this area will be an important topic over the next few years, Kritek said.

Angiotensin II improved BP

The vasopressor angiotensin II was found to improve blood pressure compared to placebo in a small trial of patients with vasodilatory shock, the majority of whom had septic shock, Kritek said.

The trial was powered to study only the effect on BP; no difference was seen in mortality or organ failure and the study was not powered to identify subsets of patients who did better on one treatment or the other, she said.

This trial excluded patients with cardiac dysfunction and previous smaller trials have identified an increased risk in this patient population. Given the difficulty in identifying which patients with septic shock are at elevated risk for cardiovascular risk, Kritek said she was hesitant to use this agent.

She also noted that the drug was expensive and unlikely to come down in price in the near future.

Paper questions ARDS guidelines

Last year, the American Thoracic Society, European Society of Intensive Medicine and the Society of Critical Care Medicine issued joint guidelines for the management of patients with ARDS. However, a study published in the Journal of the American Medical Association found that when patients were managed using higher PEEP levels and aggressive recruitment, there was an increase in cardiac arrest and a higher mortality rate. This suggests a significant downside and should be avoided, Kritek said.

Neurologic outcomes

Findings from another trial published last year found an increased risk of hypotension but no difference in survival or neurologic outcomes in patients treated with targeted temperature management for 48 vs 24 hours, Kritek said.

The REDUCE trial, published earlier this year, assessed the use of haloperidol among patients with sepsis who had a high risk of delirium. A total of 1,789 patients admitted to the ICU with an expected stay of at least 24 hours were randomly assigned to receive 1 mg or 2 mg of haloperidol vs. placebo, but there was no difference in survival or time to the onset of delirium, so there are no data to support its use, she added. – by Chris Rosenberg

Reference:

Kritek P, et al. Presented at: Hospital Medicine 2018; April 9-11, 2018; Orlando, Fla.

Disclosure: Kritek report no relevant financial disclosures.