Impact of carbohydrate-reduced nutrition in septic patients on ICU: study protocol for a prospective randomised controlled trial

Abstract

Introduction: Sepsis is defined as detrimental immune response to an infection. This overwhelming reaction often abolishes a normal reconstitution of the immune cell homeostasis that in turn increases the risk for further complications. Recent studies revealed a favourable impact of ketone bodies on resolution of inflammation. Thus, a ketogenic diet may provide an easy-to-apply and cost-effective treatment option potentially alleviating sepsis-evoked harm. This study is designed to assess the feasibility, efficiency and safety of a ketogenic diet in septic patients.

Methods and analysis: This monocentric study is a randomised, controlled and open-label trial, which is conducted on an intensive care unit of a German university hospital. As intervention enteral nutrition with reduced amount of carbohydrates (ketogenic) or standard enteral nutrition (control) is applied. The primary endpoint is the detection of ketone bodies in patients' blood and urine samples. As secondary endpoints, the impact on important safety-relevant issues (eg, glucose metabolism, lactate serum concentration, incidence of metabolic acidosis, thyroid function and 30-day mortality) and the effect on the immune system are analysed.

Ethics and dissemination: The study has received the following approvals: Ethics Committee of the Medical Faculty of Ruhr-University Bochum (No. 18-6557-BR). Results will be made available to critical care survivors, their caregivers, the funders, the critical care societies and other researchers by publication in a peer-reviewed journal.

Trial registration numbers: German Clinical Trial Register (DRKS00017710); Universal Trial Number (U1111-1237-2493).

Keywords: adult intensive & critical care; immunology; intensive & critical care; nutrition & dietetics.

Figure 1

Estimation results for sample sizes that were needed to receive a statistically significant change in the proportion of positive and negative outcomes via a binomial test scenario for various effect sizes (ie, Cohen’s d) and power values. Each curve represents the results for one specific effect size (from left to right: d=2.14; d=1.94; d=1.74; d=1.54; d=1.34), where d=2.0 is usually considered as appropriate effect size in the literature. For the assumed relatively low effect size of d=1.34, α=0.05 and 1−β=0.95 in total about 40 patients were needed.

Figure 2

Flowchart of interventional procedures on intervention and control groups with duration of each step and performed measurements. CMV, cytomegalovirus; ICU, intensive care unit; SF-36, Short Form 36.

Figure 3

Schedule of enrolment, interventions and assessments—standard protocol items: recommendations for interventional trial figure. SF 36, Short Form 36.