The supplementation of L-carnitine in septic shock patients: Systematic review and meta-analysis

Guedes, Gabriel Voltani; Minicucci, Marcos Ferreira; Tanni, Suzana Erico

doi:10.1016/j.clinsp.2022.100124

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Original articles • Clinics 77 • 2022 • https://doi.org/10.1016/j.clinsp.2022.100124 copy

The supplementation of L-carnitine in septic shock patients: Systematic review and meta-analysis

Authorship SCIMAGO INSTITUTIONS RANKINGS

HIGHLIGHTS

The objective of this review was to evaluate the effect of L-carnitine compared to placebo or Usual Care (UC) on the mortality rate in hospitalized adult septic shock patients.

Two Randomized Controlled Trials were selected for inclusion in this review

There is low-quality evidence that L-carnitine has no significant effect on 28-day mortality of septic shock patients

Abstract

Background

Sepsis and septic shock are severe and difficult-to-treat conditions with high lethality. There is interest in identifying new adjunct therapies that are effective in reducing mortality. In this context, L-carnitine has been investigated in trials as a potentially beneficial drug. Therefore, the aim of this systematic review was to assess the clinical evidence to support the use of L-carnitine in septic shock patients to reduce the risk of mortality. The objective of this review was to evaluate the effect of L-carnitine compared to placebo or Usual Care (UC) on the mortality rate in hospitalized adult septic shock patients.

Methods

The authors exclusively included randomized clinical trials that compared the use of L-carnitine versus placebo in adult (> 18 years old) septic shock patients. The outcome was a mortality rate of 28 days. This systematic review and meta-analysis were performed following the PRISMA guidelines and registered in PROSPERO with the ID CRD42020180499.

Results

Following the initial search, 4007 citations were identified, with 2701 remaining after duplicate removal. Eight citations were selected for body text reading, and two were selected for inclusion. The studies enrolled 275 patients, with 186 in the carnitine arm and 89 in the placebo arm. The effect of L-carnitine uses in septic shock patients showed a difference risk of -0.03 (95% Confidence Interval: -0.15-0.10, I² = 77%, p = 0.69) compared to placebo/in mortality rate with low quality of evidence.

Conclusions

There is low-quality evidence that the use of L-carnitine has no significant effect on reducing 28-day mortality in septic shock patients.

Keywords
L-carnitine; Septic shock; Mortality; Mitochondrial dysfunction

Study	Setting/ context	Participant characteristics	Groups	Outcomes measured	Description of main results
Jones AE, et al. 2018 USA	16 ICU	> 18y	Placebo	28-day mortality	Mortality in each group
		≤ 2 inflammatory criteria	Levocarnitine	SOFA change in 48h
		≤ 24h septic shock	6g/12h	Hospital length
		Use high dose vasopressors	12g/12h
		SOFA > 6	18g/12h
Puskarich MA, et al 2014 USA	1 ICU	> 18y	Placebo	28-day mortality	Mortality in each group
		Suspected infection	L-carnitine 12g/12h	Severe adverse event
		SOFA > 5		SOFA change in 2 points in 24h and 48h
		≥ 2 inflammatory criteria
		≤ 24h septic shock
		Use high dose vasopressors

Study	Rand omiza tion	Alloc ation	Double blind	Obser ver	Looses	Charact patient	Outco me	ITT	Sample size calculation	Early stop trial
Puskarish 2014
Jones, 2018

Certainty assessment							N° of patients		Effect		Certainty study design	Importance risk of bias
N° of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	Risk of bias	Inconsistency	Indirectness	N° of studies	Certainty study design	Importance risk of bias
Mortality (follow-up 28 days)
2²¹21 Puskarich MA, Kline JA, Krabill V, Claremont H, Jones AE. Preliminary safety and efficacy of L-carnitine infusion for the treatment of vasopressor-dependent septic shock: a randomized control trial. JPEN J Parenter Enteral Nutr. 2014;38(6):736-43.,²²22 Jones AE, Puskarich MA,Shapiro NI, Guirgis FW, Runyon M, Adams JY, et al. Effect of levocarnitine vs. placebo as an adjunctive treatment for septic shock: the rapid administration of carnitine in sepsis (RACE) randomized clinical trial. JAMA Netw Open. 2018;1(8):e186076.	Randomized clinical trials	Severe	Severe^a a High heterogeneity.	Not serious	Severe^b b Large variance of 95% CI.	None	85/186 (45.7%)	43/89 (48.3%)	RR 0.94 (0.71 to 1.23)	29 fewer per 1.000 (from 140 fewer to 111 more)	⨁◯◯◯ Very Low^a a High heterogeneity. ,^b b Large variance of 95% CI.	Critical

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[1] ⁎ Corresponding author. E-mail address: gvoltaniguedes@gmail.com (G.V. Guedes).