Azevedo, Paula Schmidt

Ballarin, Raquel Simões

Lazzarin, Taline

Minicucci, Marcos Ferreira

Pereira, Filipe Welson Leal

Tanni, Suzana Erico

English

Cadernos Espinosanos (E-Journal)

Clinics 78 (2023) 100197journal homepage: https://www.journals.elsevier.com/clinicsCommentsRole of sulfonylurea administration in sepsisand septic shock patients: A systematic reviewSepsis is an organic dysfunction caused by a dysregulated hostresponse to infection. While the septic shock is defined as sepsis withsustained hypotension despite adequate fluid resuscitation, requiringvasoactive drugs to maintain mean arterial pressure greaterthan 65 mmHg plus a serum lactate level greater than 2 mmoL/L1.Systemic vasodilatation is a critical point in the pathogenesis of sep-tic shock that could be reversed with vasoactive drugs. However, hypo-responsiveness to vasopressor agents is a common feature. A proposedmechanism for this inadequate hemodynamic response to a high dose ofvasopressors is the vascular smooth muscle membrane potential alter-ation. Potassium is a vital ion contributor to this potential, and activa-tion of the ATP-dependent Potassium (K-ATP) channel is wellunderstood to induce vasodilation and inhibit vasoconstriction. Sulfo-nylurea represents a class of medication that promotes inhibition of theK-ATP channel, which has been shown to increase vasoconstriction inseptic shock2.To clarify the effects of sulfonylureas in the treatment of septic shockpatients, we performed a Systematic Review (SR) according to the Pre-ferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) guidelines. The protocol was published on PROSPERO(ID: CRD42022369998) based on the patients of interest, the interven-tion to be studied, the comparison of interventions, and the outcome ofinterest (PICO) methodology3. Regarding the use of sulfonylureas, thePICO framework was as follows: patients, adult sepsis or septic shockpatients; intervention, use of sulfonylureas; comparison, comparisonbetween sulfonylureas administration and placebo; and outcome, themortality rate, hospital length of stay, and timing use of vasoactiveagents. The eligibility criteria for the inclusion of studies were observa-tional and randomized controlled trials. We had no restrictions onhttps://doi.org/10.1016/j.clinsp.2023.100197Received 28 February 2023; Accepted 30 March 20231807-5932/© 2023 HCFMUSP. Published by Elsevier España, S.L.U. This is an open a4.0/)publication date, language, or full-text availability. Unfortunately, wedid not find any study with the inclusion criteria to analyze the effective-ness of using sulfonylurea in septic shock patients. Limited knowledgeconsidering secondary outcomes is described in the studies, which isrelated to a potential modifiable in the biochemistry pathway of disease.However, it still unknown the effect on critical outcomes for thosepatients (Fig. 1). We did not perform a metanalysis because none of thetrials evaluated the previously proposed outcomes. However, it is essen-tial to highlight our findings.In 2005, Warrillow et al. promoted the first trial to evaluate if sulfo-nylurea restores norepinephrine responsiveness in patients with septicshock. Patients were randomized to receive glibenclamide (20 mg) or aplacebo, and after 24 hours, each patient crossed over to receive thealternative therapy. Glibenclamide failed to achieve a more significantreduction in norepinephrine dose than the placebo. There were also nosignificant changes in heart rate, mean arterial pressure, and lactate con-centration between groups4.In 2007, Morelli et al. performed a clinical study to determinewhether different doses of glibenclamide would alter norepinephrinerequirements, cardiopulmonary hemodynamics, and global oxygentransport in septic shock. Patients were randomized to receiveeither 10, 20 or 30 mg of glibenclamide. None of the doses affected car-diopulmonary hemodynamics, global oxygen transport, gas exchange,or electrolytes5.Despite the negative findings of this review, we must not disregardsulfonylureas administration to septic patients considering that no criti-cal outcome such as mortality, length of hospital stays, or time of vasoac-tive drugs requirement was evaluated. In addition, the two trials weresingle-center, with small recruited patients and enteral sulfonylureaadministration. In experimental studies, the parenteral formulation isthe most described, and considering the uncertainty of enteral absorp-tion in shock states, this can be an essential aspect.ccess article under the CC BY license (http://creativecommons.org/licenses/by/Fig. 1. Flowchart for inclusion in the systematic review.T. Lazzarin et al. Clinics 78 (2023) 100197In conclusion, more studies should be performed to evaluate betterthe effects of sulfonylureas administration in patients with sepsis andseptic shock.FundingThe authors received no financial support for the research, author-ship, and/or publication of this article.Conflicts of interestThe authors declare no conflicts of interest.References[1]. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, et al.The Third international consensus definitions for sepsis and septic shock (Sepsis-3).JAMA 2016;315(8):801.2[2]. Buckley JF, Singer M, Clapp LH. Role of KATP channels in sepsis. Cardiovasc Res2006;72(2):220–30.[3]. da Costa Santos CM, de Mattos Pimenta CA, Nobre MR. The PICO strategy for theresearch question construction and evidence search. Rev Lat Am Enfermagem2007;15(3):508–11.[4]. Warrillow S, Egi M, Bellomo R. Randomized, double-blind, placebo-controlled cross-over pilot study of a potassium channel blocker in patients with septic shock. CriticalCare Medicine 2006;34(4):980–5.[5]. Morelli A, Lange M, Ertmer C, Broeking K, Aken HV, Orecchioni A, et al. Glibencla-mide dose response in patients with septic shock: effects on norepinephrine require-ments, cardiopulmonary performance, and global oxygen transport. Shock 2007;28(5):530–5.Taline Lazzarin *, Raquel Sim~oes Ballarin ,Filipe Welson Leal Pereira, Paula Schmidt Azevedo ,Suzana Erico Tanni , Marcos Ferreira MinicucciInternal Medicine Department, Faculdade de Medicina, UniversidadeEstadual Paulista (UNESP), Botucatu, SP, Brazil*Corresponding author.E-mail address: taline.lazzarin@unesp.br (T. Lazzarin).

Role of sulfonylurea administration in sepsis and septic shock patients: A systematic review

https://www.revistas.usp.br/clinics/article/download/214079/196300

Role of sulfonylurea administration in sepsis and septic shock patients: A systematic review

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