Effects of perioperative dexmedetomidine on delayed graft function following renal transplant: a systematic review and meta-analysis
Efeitos da dexmedetomidina perioperatória na função tardia do enxerto após transplante renal: uma revisão sistemática e meta-análise
Ka Ting Ng, Wei En Lim, Wan Yi Teoh, Soo Kun Lim, Ahmad Nazran bin Fadzli, Pui San Loh
Abstract
Background
Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients.
Methods
Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports.
Results
Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52–0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32–11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%).
Conclusions
This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.
Keywords
Resumo
Introdução
A dexmedetomidina, um agonista alfa-2 adrenoceptor altamente seletivo com efeitos sedativos e analgésicos, foi sugerida em estudos recentes por possuir propriedades renoprotetoras. A dexmedetomidina pode reduzir a incidência de função tardia do enxerto e contribuir para o controle eficaz da dor pós-transplante renal. O objetivo principal desta revisão sistemática foi avaliar se a dexmedetomidina diminui a ocorrência de função tardia do enxerto em pacientes com transplante renal.
Métodos
Bancos de dados incluindo MEDLINE, EMBASE e CENTRAL foram pesquisados de forma abrangente desde o início até março de 2023. Os critérios de inclusão cobriram todos os Ensaios Clínicos Randomizados (ECRs) e estudos observacionais comparando a dexmedetomidina ao controle em pacientes adultos submetidos à cirurgia de transplante renal. As exclusões compreenderam séries de casos e relatos de casos.
Resultados
Dez ECRs envolvendo um total de 1358 pacientes atenderam aos critérios de elegibilidade para síntese de dados. Comparado ao grupo controle, o grupo dexmedetomidina demonstrou uma incidência significativamente menor de função tardia do enxerto (OR = 0,71, IC de 95% 0,52–0,97, p = 0,03, GRADE: Muito baixo, I2 = 0%). A dexmedetomidina também prolongou significativamente o tempo para o início da analgesia de resgate (MD = 6,73, IC de 95% 2,32–11,14, p = 0,003, GRADE: Muito baixo, I2 = 93%) e reduziu o consumo geral de morfina após o transplante renal (MD = -5,43, IC de 95% -7,95 a -2,91, p < 0,0001, GRADE: Muito baixo, I2 = 0%). O grupo dexmedetomidina apresentou uma redução significativa na frequência cardíaca (MD = -8,15, IC de 95% -11,45 a -4,86, p < 0,00001, GRADE: Muito baixo, I2 = 84%) e pressão arterial média em comparação ao grupo controle (MD = -6,66, IC de 95% -11,27 a -2,04, p = 0,005, GRADE: Muito baixo, I2 = 87%).
Conclusões
Esta meta-análise sugere que a dexmedetomidina pode potencialmente reduzir a incidência de função tardia do enxerto e oferece um perfil de analgesia superior em comparação ao controle em adultos submetidos a transplantes renais. No entanto, o alto grau de heterogeneidade e o tamanho inadequado da amostra ressaltam a necessidade de futuros ensaios com poder adequado para confirmar essas descobertas.
Palavras-chave
Referências
1. Elfein J. Organ transplant statistics worldwide 2021 [Internet]. Statista. 2023 [cited 2023 Mar 31]. Available from: https:// www.statista.com/statistics/398645/global-estimation-oforgan-transplantations/.
2. Gaston RS. Improving Long-term Outcomes in Kidney Transplantation: Towards A New Paradigm of Post-transplant Care in The United States. Trans Am Clin Climatol Assoc. 2016;127:350−61.
3. Shan XS, Hu LK, Wang Y, et al. Effect of Perioperative Dexmedetomidine on Delayed Graft Function Following a DonationAfter-Cardiac Death Kidney Transplant: A Randomized Clinical Trial. JAMA Netw Open. 2022;5. e2215217-e2215217.
4. Wu WK, Famure O, Li Y, Kim SJ. Delayed graft function and the risk of acute rejection in the modern era of kidney transplantation. Kidney International. 2015;88:851−8.
5. Khalkhali HR, Ghafari A, Hajizadeh E, Kazemnejad A. Risk factors of long-term graft loss in renal transplant recipients with chronic allograft dysfunction. Exp Clin Transplant. 2010;8: 277−82.
6. Lee S. Dexmedetomidine: Present and future directions. Korean J Anesthesiol. 2019;72:323−30.
7. Yang N, Luo M, Li R, et al. Blockage of JAK/STAT signalling attenuates renal ischaemia-reperfusion injury in rat. Nephrol Dial Transplant. 2008;23:91−100.
8. Gu J, Sun P, Zhao H, et al. Dexmedetomidine provides renoprotection against ischemia-reperfusion injury in mice. Crit Care. 2011;15:1−11.
9. Zhao Y, He J, Yu N, Jia C, Wang S. Mechanisms of Dexmedetomidine in Neuropathic Pain. Front Neurosci. 2020;14:330.
10. Castillo RL, Ibacache M, Cortínez I, et al. Dexmedetomidine Improves Cardiovascular and Ventilatory Outcomes in Critically Ill Patients: Basic and Clinical Approaches. Front Pharmacol. 2020;10:1641.
11. Chen J, Perez R, Mattos AM, et al. Perioperative Dexmedetomidine Improves Outcomes of Kidney Transplant. Clin Transl Sci. 2020;13:1279−87.
12. Negi S, Sen I, Arya V, Sharma A. Dexmedetomidine versus fentanyl as coadjuvants of balanced anaesthesia technique in renal transplant recipients. Middle East J Anaesthesiol. 2014;22: 549−57.
13. Yang P, Luo Y, Lin L, Zhang H, Liu Y, Li Y. The efficacy of transversus abdominis plane block with or without dexmedetomidine for postoperative analgesia in renal transplantation. A randomized controlled trial. Int J Surgery. 2020;79:196−201.
14. Mesbah M, Zeraatian S, Houshyar P, et al. Assess of The Effects of Dexmedetomidine on Renal Function In Renal Transplant Recipients. Int J Cur Adv Res. 2018;7:13919−21.
15. Park JH, Koo BN, Kim MS, Shin D, Kwak YL. Effects of intraoperative dexmedetomidine infusion on renal function in elective living donor kidney transplantation: a randomized controlled trial. Can J Anesth. 2022;69:448−59.
16. Deeks JJ, Higgins JP, Altman DG, on behalf of the Cochrane Statistical Methods Group. Analysing data and undertaking metaanalyses. In: Higgins JPT, Thomas J, Chandler J, Cumpston M, Li T, Page MJ, et al., editors. Cochrane Handbook for Systematic Reviews of Interventions [Internet]. 1st ed. Wiley; 2019 [cited 2023 April 09]. p. 24184. Available from: https://onlinelibrary. wiley.com/. doi: 10.1002/9781119536604.ch10.
17. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71.
18. Higgins JPT, Altman DG, Gøtzsche PC, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011: 343.
19. GDT: GRADEpro Guideline Development Tool [Software]. McMaster University and Evidence Prime, 2022. Available from gradepro.org.
20. Review Manager (RevMan) [Computer program]. Version 5.4. The Cochrane Collaboration, 2020.
21. Wan X, Wang W, Liu J, Tong T. Estimating the sample mean and standard deviation from the sample size, median, range and/or interquartile range. BMC Med Res Methodol. 2014;14:135.
22. Chopade MN, Narani KK, Sood J, et al. Study of effect of intraoperative low dose continuous dexmedetomidine infusion on hemodynamic parameters and depth of anaesthesia in patients undergoing renal transplantation. Eur J Mol Clin Med. 2022; 20:4050−9.
23. Wang YC, Wang MJ, Lee CY, et al. Effects of perioperative dexmedetomidine infusion on renal function and microcirculation in kidney transplant recipients: a randomised controlled trial. Ann Med. 2022;54:1233−43.
24. Wei X, Zhou S, Gao W, Mao J, Shu S, Chai X. Application of Dexmedetomidine in Anesthesia for Recipients in Living Related Renal Transplantation. Organ Transplantation. 2015;6:411−4.
25. Liu Z, Jin Y, Feng C, Liu G, Wang Y, Zhao X. Renoprotective Effect of Intraoperative Dexmedetomidine in Renal Transplantation. Comput Math Methods Med. 2022;2022:1−11.
26. Siedlecki A, Irish W, Brennan DC. Delayed graft function in the kidney transplant. Am J Transplant. 2011;11:2279−96.
27. Salvadori M, Rosso G, Bertoni E. Update on ischemia-reperfusion injury in kidney transplantation: Pathogenesis and treatment. World J Transplant. 2015;5:52−67.
28. Srinivas TR, Schold JD, Meier-Kriesche HU. CHAPTER 105 ‒ Outcomes of Renal Transplantation. In: Floege J, Johnson RJ, Feehally J, editors. Comprehensive Clinical Nephrology (Fourth Edition) [Internet]. Philadelphia: Mosby; 2010. p. 1222-31.
29. Kayler L, Yu X, Cortes C, Lubetzky M, Friedmann P. Impact of Cold Ischemia Time in Kidney Transplants From Donation After Circulatory Death Donors. Transplant Direct. 2017;3: e177.
30. Toufeeq Khan TF, Ahmad N, Serageldeen AS, Fourtounas K. Implantation Warm Ischemia Time in Kidney Transplant Recipients: Defining Its Limits and Impact on Early Graft Function. Ann Transplant [Internet]. 2019;24:432.. [cited 2023 Mar 28]. Available from: https://pmc/articles/PMC6676983/.
31. McLaren AJ, Jassem W, Gray DW, Fuggle SV, Welsh KI, Morris PJ. Delayed graft function: risk factors and the relative effects of early function and acute rejection on long-term survival in cadaveric renal transplantation. Clinical transplantation. 1999;13:266−72.
32. Ponticelli C, Reggiani F, Moroni G. Delayed Graft Function in Kidney Transplant: Risk Factors, Consequences and Prevention Strategies. J Pers Med. 2022;12:1557.
33. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001;14:13−21.
34. McCormack HM, Horne DJ, Sheather S. Clinical applications of visual analogue scales: a critical review. Psychol Med. 1988;18:1007−19.
35. Gould D, Kelly D, Goldstone L, Gammon J. Examining the validity of pressure ulcer risk assessment scales: developing and using illustrated patient simulations to collect the data. J Clin Nurs. 2001;10:697−706.
36. National Institute on Drug Abuse. Fentanyl DrugFacts [Internet]. National Institute on Drug Abuse. National Institute of Health; 2021. [cited 2023 April 09]. Available from: https://nida.nih. gov/publications/drugfacts/fentanyl.
37. Kaur M, Singh PM. Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth Essays Res. 2011;5:128 −33.
38. Gerlach AT, Blais DM, Jones GM, et al. Predictors of dexmedetomidine-associated hypotension in critically ill patients. Int J Crit Illn Inj Sci. 2016;6:109−14.
39. Ice CJ, Personett HA, Frazee EN, Dierkhising RA, Kashyap R, Oeckler RA. Risk Factors for Dexmedetomidine-Associated Hemodynamic Instability in Noncardiac Intensive Care Unit Patients. Anesth Analg. 2016;122:462−9.
40. Constantin JM, Momon A, Mantz J, et al. Efficacy and safety of sedation with dexmedetomidine in critical care patients: a meta-analysis of randomized controlled trials. Anaesth Crit Care Pain Med. 2016;35:7−15.
41. Li Q, Chen C, Chen X, Han M, Li J. Dexmedetomidine attenuates renal fibrosis via a2-adrenergic receptor-dependent inhibition of cellular senescence after renal ischemia/reperfusion. Life Sci. 2018;207:1−8.
42. Sellares J, de Freitas DG, Mengel M, et al. Understanding the causes of kidney transplant failure: the dominant role of antibody-mediated rejection and nonadherence. Am J Transplant. 2012;12:388−99.
43. Wang K, Wu M, Xu J, et al. Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: systematic review and meta-analysis. Br J Anaesth. 2019;123:777−94.
44. Chen R, Wang H, Song L, et al. Predictors and one-year outcomes of patients with delayed graft function after deceased donor kidney transplantation. BMC Nephrol. 2020;526:1−10.
45. Vella J. Kidney transplantation in adults: Risk factors for graft failure. In: UpToDate, Brennan DC, Legendre C (Ed), Wolters Kluwer [Internet]. [cited 2023 April 09]. Available from: https://www.uptodate.com/contents/kidney-transplantationin-adults-risk-factors-for-graft-failure.
46. Postalcioglu M, Kaze AD, Byun BC, et al. Association of Cold Ischemia Time With Acute Renal Transplant Rejection. Transplantation. 2018;102:1188−94.
47. Schold JD, Augustine JJ, Huml AM, et al. Effects of body mass index on kidney transplant outcomes are significantly modified by patient characteristics. Am J Transplant. 2021;21:751−65.
48. Loomba RS, Villarreal EG, Dhargalkar J, et al. The effect of dexmedetomidine on renal function after surgery: A systematic review and meta-analysis. J Clin Pharm Ther. 2022;47:287−97.
Submetido em:
24/08/2023
Aceito em:
19/06/2024
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email