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Endocrine, Metabolic & Immune Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Systematic Review Article

The Effect of L-Carnitine on Mortality Rate in Septic Patients: A Systematic Review and Meta-Analysis on Randomized Clinical Trials

Author(s): Hamed Abdollahi, Mina Abdolahi, Mohsen Sedighiyan and Arash Jafarieh*

Volume 21, Issue 4, 2021

Published on: 27 July, 2020

Page: [673 - 681] Pages: 9

DOI: 10.2174/1871530320666200727150450

Price: $65

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Abstract

Background: Recent clinical trial studies have reported that L-carnitine supplementation can reduce the mortality rate in patients with sepsis, but there are no definitive results in this context. The current systematic review and meta-analysis aimed to evaluate the effect of L-carnitine supplementation on 28-day and one-year mortality in septic patients.

Methods: A systematic search conducted on Pubmed, Scopus and Cochrane Library databases up to June 2019 without any language restriction. The publications were reviewed based on the Cochrane handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA). To compare the effects of L-carnitine with placebo, Risk Ratio (RR) with 95% confidence intervals (CI) were pooled according to the random effects model.

Results: Across five enrolled clinical trials, we found that L-carnitine supplementation reduce one-year mortality in septic patients with SOFA> 12 (RR: 0.68; 95% CI: 0.49 to 0.96; P= 0.03) but had no significant effect on reducing 28-day mortality ((RR: 0.93; 95% CI: 0.68 to 1.28; P= 0.65) compared to placebo. Finally, we observed that based on current trials, L-carnitine supplementation may not have clinically a significant effect on mortality rate.

Conclusion: L-carnitine patients with higher SOFA score can reduce the mortality rate. However, the number of trials, study duration and using a dosage of L-carnitine are limited in this context and further large prospective trials are required to clarify the effect of L-carnitine on mortality rate in septic patients.

Keywords: L-carnitine, sepsis, mortality, SOFA, clinical trial, meta-analysis.

Graphical Abstract

[1]
Gaieski, D.F.; Edwards, J.M.; Kallan, M.J.; Carr, B.G. Benchmarking the incidence and mortality of severe sepsis in the United States. Crit. Care Med., 2013, 41(5), 1167-1174.
[http://dx.doi.org/10.1097/CCM.0b013e31827c09f8] [PMID: 23442987]
[2]
Shankar-Hari, M.; Phillips, G.S.; Levy, M.L.; Seymour, C.W.; Liu, V.X.; Deutschman, C.S.; Angus, D.C.; Rubenfeld, G.D.; Singer, M. Sepsis definitions task force. Developing a new definition and assessing new clinical criteria for septic shock: for the third international consensus definitions for Sepsis and Septic Shock (Sepsis-3). JAMA, 2016, 315(8), 775-787.
[http://dx.doi.org/10.1001/jama.2016.0289] [PMID: 26903336]
[3]
Rhodes, A.; Evans, L.E.; Alhazzani, W.; Levy, M.M.; Antonelli, M.; Ferrer, R.; Kumar, A.; Sevransky, J.E.; Sprung, C.L.; Nunnally, M.E.; Rochwerg, B.; Rubenfeld, G.D.; Angus, D.C.; Annane, D.; Beale, R.J.; Bellinghan, G.J.; Bernard, G.R.; Chiche, J.D.; Coopersmith, C.; De Backer, D.P.; French, C.J.; Fujishima, S.; Gerlach, H.; Hidalgo, J.L.; Hollenberg, S.M.; Jones, A.E.; Karnad, D.R.; Kleinpell, R.M.; Koh, Y.; Lisboa, T.C.; Machado, F.R.; Marini, J.J.; Marshall, J.C.; Mazuski, J.E.; McIntyre, L.A.; McLean, A.S.; Mehta, S.; Moreno, R.P.; Myburgh, J.; Navalesi, P.; Nishida, O.; Osborn, T.M.; Perner, A.; Plunkett, C.M.; Ranieri, M.; Schorr, C.A.; Seckel, M.A.; Seymour, C.W.; Shieh, L.; Shukri, K.A.; Simpson, S.Q.; Singer, M.; Thompson, B.T.; Townsend, S.R.; Van der Poll, T.; Vincent, J.L.; Wiersinga, W.J.; Zimmerman, J.L.; Dellinger, R.P. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016. Intensive Care Med., 2017, 43(3), 304-377.
[http://dx.doi.org/10.1007/s00134-017-4683-6] [PMID: 28101605]
[4]
Dellinger, R.P.; Levy, M.M.; Rhodes, A.; Annane, D.; Gerlach, H.; Opal, S.M.; Sevransky, J.E.; Sprung, C.L.; Douglas, I.S.; Jaeschke, R.; Osborn, T.M.; Nunnally, M.E.; Townsend, S.R.; Reinhart, K.; Kleinpell, R.M.; Angus, D.C.; Deutschman, C.S.; Machado, F.R.; Rubenfeld, G.D.; Webb, S.; Beale, R.J.; Vincent, J.L.; Moreno, R. Surviving sepsis campaign guidelines committee including the pediatric subgroup. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock, 2012. Intensive Care Med., 2013, 39(2), 165-228.
[http://dx.doi.org/10.1007/s00134-012-2769-8] [PMID: 23361625]
[5]
Mouncey, P.R.; Osborn, T.M.; Power, G.S.; Harrison, D.A.; Sadique, M.Z.; Grieve, R.D.; Jahan, R.; Harvey, S.E.; Bell, D.; Bion, J.F.; Coats, T.J.; Singer, M.; Young, J.D.; Rowan, K.M. ProMISe Trial Investigators. Trial of early, goal-directed resuscitation for septic shock. N. Engl. J. Med., 2015, 372(14), 1301-1311.
[http://dx.doi.org/10.1056/NEJMoa1500896] [PMID: 25776532]
[6]
Oedorf, K.; Day, D.E.; Lior, Y.; Novack, V.; Sanchez, L.D.; Wolfe, R.E.; Kirkegaard, H.; Shapiro, N.I.; Henning, D.J. Serum lactate predicts adverse outcomes in emergency department patients with and without infection. West. J. Emerg. Med., 2017, 18(2), 258-266.
[http://dx.doi.org/10.5811/westjem.2016.10.31397] [PMID: 28210362]
[7]
Gessner, B.D.; Gillingham, M.B.; Birch, S.; Wood, T.; Koeller, D.M. Evidence for an association between infant mortality and a carnitine palmitoyltransferase 1A genetic variant. Pediatrics, 2010, 126(5), 945-951.
[http://dx.doi.org/10.1542/peds.2010-0687] [PMID: 20937660]
[8]
Hatamkhani, S.; Karimzadeh, I.; Elyasi, S.; Farsaie, S.; Khalili, H. Carnitine and sepsis: a review of an old clinical dilemma. J. Pharm. Pharm. Sci., 2013, 16(3), 414-423.
[http://dx.doi.org/10.18433/J3JS4C] [PMID: 24021290]
[9]
Longo, N.; Frigeni, M.; Pasquali, M. Carnitine transport and fatty acid oxidation. Biochim. Biophys. Acta, 2016, 1863(10), 2422-2435.
[http://dx.doi.org/10.1016/j.bbamcr.2016.01.023]
[10]
Chung, K-P.; Chen, G-Y.; Chuang, T-Y.; Huang, Y-T.; Chang, H-T.; Chen, Y-F.; Liu, W.L.; Chen, Y.J.; Hsu, C.L.; Huang, M.T.; Kuo, C.H.; Yu, C.J. Increased plasma acetylcarnitine in sepsis is associated with multiple organ dysfunction and mortality: a multicenter cohort study. Crit. Care Med., 2019, 47(2), 210-218.
[http://dx.doi.org/10.1097/CCM.0000000000003517] [PMID: 30379669]
[11]
Weiss, S.L.; Haymond, S.; Ralay Ranaivo, H.; Wang, D.; De Jesus, V.R.; Chace, D.H.; Wainwright, M.S. Evaluation of asymmetric dimethylarginine, arginine, and carnitine metabolism in pediatric sepsis. Pediatr. Crit. Care Med., 2012, 13(4), e210-e218.
[http://dx.doi.org/10.1097/PCC.0b013e318238b5cd] [PMID: 22460770]
[12]
Takeyama, N.; Takagi, D.; Matsuo, N.; Kitazawa, Y.; Tanaka, T. Altered hepatic fatty acid metabolism in endotoxicosis: effect of L-carnitine on survival. Am. J. Physiol., 1989, 256(1 Pt 1), E31-E38.
[PMID: 2521428]
[13]
Puskarich, M.A.; Kline, J.A.; Krabill, V.; Claremont, H.; Jones, A.E. 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), 736-743.
[http://dx.doi.org/10.1177/0148607113495414] [PMID: 23851424]
[14]
Gasparetto, A.; Corbucci, G.G.; De Blasi, R.A.; Antonelli, M.; Bagiella, E.; D’Iddio, S.; Trevisani, C. Influence of acetyl-L-carnitine infusion on haemodynamic parameters and survival of circulatory-shock patients. Int. J. Clin. Pharmacol. Res., 1991, 11(2), 83-92.
[PMID: 1879992]
[15]
Gallo, L.L.; Tian, Y.; Orfalian, Z.; Fiskum, G. Amelioration of popolysaccharide-induced sepsis in rats by free and esterified carnitine. Mediators Inflamm., 1993, 2(7), S51-S56.
[http://dx.doi.org/10.1155/S0962935193000766] [PMID: 18475572]
[16]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. PRISMA group; Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement., Ann. Intern. Med., 2009, 151(4), 264-269, W64..
[http://dx.doi.org/ 10.7326/0003-4819-151-4-200908180-00135 ] [PMID: 19622511 ]
[17]
Higgins, J.P.; Green, S. Cochrane handbook for systematic reviews of interventions; John Wiley & Sons, 2011.
[18]
Borenstein, M.; Hedges, L.V.; Higgins, J.P.; Rothstein, H.R. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res. Synth. Methods, 2010, 1(2), 97-111.
[http://dx.doi.org/10.1002/jrsm.12] [PMID: 26061376]
[19]
Jones, AE; Puskarich, MA; Shapiro, NI; Guirgis, FW; Runyon, M; Adams, JY .Effect of levocarnitine vs placebo as an adjunctive treatment for septic shock: the rapid administration of carnitine in sepsis (RACE) randomized clinical trial. JAMA Network Open, 2018, 1(8), e186076-e..
[20]
Puskarich, M.A.; Evans, C.R.; Karnovsky, A.; Das, A.K.; Jones, A.E.; Stringer, K.A. Septic shock nonsurvivors have persistently elevated acylcarnitines following carnitine supplementation. Shock, 2018, 49(4), 412-419.
[http://dx.doi.org/10.1097/SHK.0000000000000997] [PMID: 29384504]
[21]
Evans, C.R.; Karnovsky, A.; Puskarich, M.A.; Michailidis, G.; Jones, A.E.; Stringer, K.A. Untargeted metabolomics differentiates l-carnitine treated septic shock 1-year survivors and nonsurvivors. J. Proteome Res., 2019, 18(5), 2004-2011.
[http://dx.doi.org/10.1021/acs.jproteome.8b00774] [PMID: 30895797]
[22]
Puskarich, M.A.; Finkel, M.A.; Karnovsky, A.; Jones, A.E.; Trexel, J.; Harris, B.N.; Stringer, K.A. Pharmacometabolomics of l-carnitine treatment response phenotypes in patients with septic shock. Ann. Am. Thorac. Soc., 2015, 12(1), 46-56.
[http://dx.doi.org/10.1513/AnnalsATS.201409-415OC] [PMID: 25496487]
[23]
Sedighiyan, M.; Abdolahi, M.; Taheri, E.; Qorbani, M.; Omidian, P.; Hosseini, S. The French maritime pine bark extract reduce metabolic syndrome risk and improve body composition in obesity: a new clinical approach. Acta Med. Iran., 2018, 56(3), 196-203.
[24]
Soveyd, N.; Abdolahi, M.; Bitarafan, S.; Tafakhori, A.; Sarraf, P.; Togha, M.; Okhovat, A.A.; Hatami, M.; Sedighiyan, M.; Djalali, M.; Mohammadzadeh Honarvar, N. Molecular mechanisms of omega-3 fatty acids in the migraine headache. Iran. J. Neurol., 2017, 16(4), 210-217.
[PMID: 29736227]
[25]
Sedighiyan, M.; Abdolahi, M.; Honarvar, N.M.; Hosseini, B.; Djafarian, K. Curcumin a novel agent targeting inflammatory pathways in obesity. J. Nutr. Sci. & Diet., 2016, 2(4)
[26]
Honarvar, N.M.; Harrirchian, M.H.; Koohdani, F.; Siassi, F.; Jafari Rad, S.; Abdolahi, M.; Bitarafan, S.; Salehi, E.; Sahraian, M.A.; Eshraghian, M.R.; Saboor-Yarghi, A.A. In vitro effect of human serum and fetal calf serum on CD4+ T cells proliferation in response to myelin oligodendrocyte glycoprotein (MOG) in correlation with RBP/TTR ratio in multiple sclerotic patients. J. Mol. Neurosci., 2013, 50(3), 571-576.
[http://dx.doi.org/10.1007/s12031-013-9999-2] [PMID: 23564281]
[27]
Eaton, S.; Fukumoto, K.; Stefanutti, G.; Spitz, L.; Zammit, V.; Pierro, A. Myocardial carnitine palmitoyltransferase I as a target for oxidative modification in inflammation and sepsis; Portland Press Limited, 2003.
[http://dx.doi.org/10.1042/bst0311133]
[28]
Belsky, J.B.; Wira, C.R.; Jacob, V.; Sather, J.E.; Lee, P.J. A review of micronutrients in sepsis: the role of thiamine, l-carnitine, vitamin C, selenium and vitamin D. Nutr. Res. Rev., 2018, 31(2), 281-290.
[http://dx.doi.org/10.1017/S0954422418000124] [PMID: 29984680]
[29]
Kompare, M.; Rizzo, W.B., Eds.; Mitochondrial fatty-acid oxidation disorders. Seminars in pediatric neurology; Elsevier, 2008.
[30]
Longo, N.; Amat di San Filippo, C.; Pasquali, M., Eds.; Disorders of carnitine transport and the carnitine cycle. American Journal of Medical Genetics Part C: Seminars in Medical Genetics; Wiley Online Library, 2006.
[31]
Kawasaki, N.; Lee, J-D.; Shimizu, H.; Ueda, T. Experimental studies long-term l-carnitine treatment prolongs the survival in rats with adriamycin-induced heart failure. J. Card. Fail., 1996, 2(4), 293-299.
[http://dx.doi.org/10.1016/S1071-9164(96)80016-9] [PMID: 8989644]
[32]
Vincent, J-L.; Moreno, R.; Takala, J.; Willatts, S.; De Mendonça, A.; Bruining, H.; Reinhart, C.K.; Suter, P.M.; Thijs, L.G. The SOFA (Sepsis-related organ failure assessment) score to describe organ dysfunction/failure. Intensive Care Med., 1996, 22(7), 707-710.
[http://dx.doi.org/10.1007/BF01709751] [PMID: 8844239]
[33]
Singer, A.J.; Ng, J.; Thode, H.C., Jr; Spiegel, R.; Weingart, S. Quick SOFA scores predict mortality in adult emergency department patients with and without suspected infection. Ann. Emerg. Med., 2017, 69(4), 475-479.
[http://dx.doi.org/10.1016/j.annemergmed.2016.10.007] [PMID: 28110990]
[34]
Ferreira, F.L.; Bota, D.P.; Bross, A.; Mélot, C.; Vincent, J-L. Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA, 2001, 286(14), 1754-1758.
[http://dx.doi.org/10.1001/jama.286.14.1754] [PMID: 11594901]
[35]
Nüesch, E.; Trelle, S.; Reichenbach, S.; Rutjes, A.W.; Tschannen, B.; Altman, D.G.; Egger, M.; Jüni, P. Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ, 2010, 341, c3515.
[http://dx.doi.org/10.1136/bmj.c3515] [PMID: 20639294]

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