Does dexmedetomidine reduce the risk of acute kidney injury after cardiac surgery? A meta-analysis of randomized controlled trials
A dexmedetomidina reduz o risco de lesão renal aguda após cirurgia cardíaca? Uma meta-análise de ensaios clínicos randomizados
Chunxiao Zha, Shuo Li, Huiquan Zhan, MengqiGa
Abstract
Background
Acute Kidney Injury (AKI) is a common complication after cardiac surgery and has been associated with poor outcomes. Dexmedetomidine (DEX) has been shown to confer direct renoprotection based on some animal and clinical studies, but data from other trials came to the opposite conclusion following cardiac surgery. This meta-analysis was conducted to evaluate the effects of perioperative DEX administration on the occurrence of AKI and the outcomes after cardiac surgery.
Methods
We searched databases including EMBASE, PubMed, and Cochrane CENTRAL for Randomized Controlled Trials (RCTs) focused on DEX for AKI in adult patients after cardiac surgery. The primary outcome was incidence of AKI. Secondary outcomes were Mechanical Ventilation (MV) duration, Intensive Care Unit (ICU) Length Of Stay (LOS), hospital LOS and mortality.
Results
Fifteen trials enrolling 2907 study patients were collected in the meta-analyses. Compared with controls, DEX reduced the incidence of postoperative AKI (Odds Ratio [OR = 0.66]; 95% Confidence Interval [95% CI 0.48–0.91]; p = 0.01), and there was no significant difference between groups in postoperative mortality (OR = 0.63; 95% CI 0.32–1.26; p = 0.19), MV duration (Weighted Mean Difference [WMD = -0.44]; 95% CI -1.50–0.63; p = 0.42), ICU LOS (WMD = -1.19; 95% CI -2.89–0.51; p = 0.17), and hospital LOS (WMD = -0.31; 95% CI -0.76–0.15; p = 0.19).
Conclusions
Perioperative DEX reduced the incidence of postoperative AKI in adult patients undergoing cardiac surgery. No significant decrease existed in mortality, MV duration, ICU LOS and hospital LOS owing to DEX administration.
Keywords
Resumo
Introdução
Lesão Renal Aguda (LRA) é uma complicação comum após cirurgia cardíaca e tem sido associada a resultados ruins. Foi demonstrado que a dexmedetomidina (DEX) confere renoproteção direta com base em alguns estudos clínicos e em animais, mas dados de outros ensaios chegaram à conclusão oposta após cirurgia cardíaca. Esta meta-análise foi realizada para avaliar os efeitos da administração perioperatória de DEX na ocorrência de LRA e nos resultados após cirurgia cardíaca.
Métodos
Lesão Renal Aguda (LRA) é uma complicação comum após cirurgia cardíaca e tem sido associada a resultados ruins. Foi demonstrado que a dexmedetomidina (DEX) confere renoproteção direta com base em alguns estudos clínicos e em animais, mas dados de outros ensaios chegaram à conclusão oposta após cirurgia cardíaca. Esta meta-análise foi realizada para avaliar os efeitos da administração perioperatória de DEX na ocorrência de LRA e nos resultados após cirurgia cardíaca.
Resultados
Quinze ensaios envolvendo 2.907 pacientes do estudo foram coletados nas meta-análises. Em comparação com os controles, a DEX reduziu a incidência de LRA pós-operatória (Odds Ratio [OR = 0,66]; intervalo de confiança de 95% [IC 95% 0,48–0,91]; p = 0,01), e não houve diferença significativa entre os grupos na mortalidade pós-operatória ( OR = 0,63; IC 95% 0,32–1,26; p = 0,19), duração da VM (diferença média ponderada [DMP = -0,44]; IC 95% -1,50–0,63; p = 0,42), permanência na UTI (DMP = -1,19; IC 95% -2,89–0,51; p = 0,17) e tempo de permanência hospitalar (ADM = -0,31; IC 95% -0,76–0,15; p = 0,19).
Conclusão
A DEX perioperatória reduziu a incidência de LRA pós-operatória em pacientes adultos submetidos à cirurgia cardíaca. Não houve diminuição significativa na mortalidade, duração da VM, permanência na UTI e internação hospitalar devido à administração de DEX.
Palavras-chave
Referências
1. Wang Y, Bellomo R. Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment. Nat Rev Nephrol. 2017;13:697−711.
2. Ortega-Loubon C, Fernandez-Molina M, Carrascal-Hinojal Y, et al. Cardiac surgery-associated acute kidney injury. Ann Card Anaesth. 2016;19:687−98.
3. Guan C, Li C, Xu L, et al. Risk factors of cardiac surgery-associated acute kidney injury: development and validation of a perioperative predictive nomogram. J Nephrol. 2019;32:937−45.
4. Ranucci M, Ambrogi F, Pistuddi V. Cardiac surgery associated acute kidney injury and the role of cardiopulmonary bypass technique. J Thorac Cardiovasc Surg. 2019;157:301.
5. Liu D, Liu B, Liang Z, et al. Acute Kidney Injury following Cardiopulmonary Bypass: A Challenging Picture. Oxid Med Cell Longev. 2021;2021:8873581.
6. Meersch M, Schmidt C, Hoffmeier A, et al. Prevention of cardiac surgery-associated AKI by implementing the KDIGO guidelines in high-risk patients identified by biomarkers: the PrevAKI randomized controlled trial. Intensive Care Med. 2017;43:1551−61.
7. Kullmar M, Zarbock A, Engelman DT, et al. Prevention of acute € kidney injury. Crit Care Clin. 2020;36:691−704.
8. Couturier C, Maillard N, Mariat C, et al. Prevention of cardiac surgery-associated acute kidney injury by risk stratification using (TIMP-2)*(IGFBP7). Biomark Med. 2021;15:1201−10.
9. Presta P, Bolignano D, Coppolino G, et al. Antecedent ACE-inhibition, inflammatory response, and cardiac surgery associated acute kidney injury. Rev Cardiovasc Med. 2021;22:207−13.
10. Li S, Fu S, Xiao Y, et al. Recent Perioperative Pharmacological Prevention of Acute Kidney Injury after Cardiac Surgery: A Narrative Review. Am J Cardiovasc Drugs. 2017;17:17−25.
11. Weerink MAS, Struys M, Hannivoort LN, et al. Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine. Clin Pharmacokinet. 2017;56:893−913.
12. Gallego-Ligorit L, Vives M, Valles-Torres J, et al. Use of Dexme- detomidine in Cardiothoracic and Vascular Anesthesia. J Cardiothorac Vasc Anesth. 2018;32:1426−38.
13. Zhao Y, Feng X, Li B, et al. Dexmedetomidine Protects Against Lipopolysaccharide-Induced Acute Kidney Injury by Enhancing Autophagy Through Inhibition of the PI3K/AKT/mTOR Pathway. Front Pharmacol. 2020;11:128.
14. Feng X, Guan W, Zhao Y, et al. Dexmedetomidine ameliorates lipopolysaccharide-induced acute kidney injury in rats by inhibiting inflammation and oxidative stress via the GSK-3b/Nrf2 signaling pathway. J Cell Physiol. 2019;234:18994−9009.
15. Wang Z, Wu J, Hu Z, et al. Dexmedetomidine Alleviates Lipopolysaccharide-Induced Acute Kidney Injury by Inhibiting p75NTR-Mediated Oxidative Stress and Apoptosis. Oxid Med Cell Longev. 2020;2020:5454210. 16. Tang C, Hu Y, Gao J, et al. Dexmedetomidine pretreatment attenuates myocardial ischemia reperfusion induced acute kidney injury and endoplasmic reticulum stress in human and rat. Life Sci. 2020;257:118004.
17. Cho JS, Shim JK, Soh S, et al. Perioperative dexmedetomidine reduces the incidence and severity of acute kidney injury following valvular heart surgery. Kidney Int. 2016;89:693−700.
18. Balkanay OO, Goksedef D, Omeroglu SN, et al. The dose-related effects of dexmedetomidine on renal functions and serum neutrophil gelatinase-associated lipocalin values after coronary artery bypass grafting: a randomized, triple-blind, placebocontrolled study. Interact Cardiovasc Thorac Surg. 2015;20: 209−14.
19. Zhai M, Kang F, Han M, et al. The effect of dexmedetomidine on renal function in patients undergoing cardiac valve replacement under cardiopulmonary bypass: A double-blind randomized controlled trial. J Clin Anesth. 2017;40:33−8.
20. Peng K, Li D, Applegate 2nd RL, et al. Effect of dexmedetomidine on cardiac surgery-associated acute kidney injury: a metaanalysis with trial sequential analysis of randomized controlled trials. J Cardiothorac Vasc Anesth. 2020;34:603−13.
21. Liu Y, Sheng B, Wang S, et al. Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta-analysis of randomized controlled trials. BMC Anesthesiol. 2018;18:7.
22. Chen X, Huang T, Cao X, et al. Comparative efficacy of drugs for preventing acute kidney injury after cardiac surgery: a network meta-analysis. Am J Cardiovasc Drugs. 2018;18:49−58.
23. Turan A, Duncan A, Leung S, et al. Dexmedetomidine for reduction of atrial fibrillation and delirium after cardiac surgery (DECADE): a randomised placebo-controlled trial. Lancet. 2020;396:177−85.
24. Subramaniam B, Shankar P, Shaefi S, et al. Effect of intravenous acetaminophen vs placebo combined with propofol or dexmedetomidine on postoperative delirium among older patients following cardiac surgery: The DEXACET Randomized Clinical Trial. Jama. 2019;321:686−96.
25. Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
26. Hozo SP, Djulbegovic B, Hozo I. Estimating the mean and variance from the median, range, and the size of a sample. BMC Med Res Methodol. 2005;5:13.
27. Djaiani G, Silverton N, Fedorko L, et al. Dexmedetomidine versus Propofol Sedation Reduces Delirium after Cardiac Surgery: A Randomized Controlled Trial. Anesthesiology. 2016;124:362−8.
28. Li X, Yang J, Nie XL, et al. Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: A randomized controlled trial. PLoS One. 2017;12:e0170757.
29. Liu X, Zhang K, Wang W, et al. Dexmedetomidine sedation reduces atrial fibrillation after cardiac surgery compared to propofol: a randomized controlled trial. Crit Care. 2016;20: 298.
30. Park JB, Bang SH, Chee HK, et al. Efficacy and safety of dexmedetomidine for postoperative delirium in adult cardiac surgery on cardiopulmonary bypass. Korean J Thorac Cardiovasc Surg. 2014;47:249−54.
31. Shehabi Y, Grant P, Wolfenden H, et al. Prevalence of delirium with dexmedetomidine compared with morphine-based therapy after cardiac surgery: a randomized controlled trial (DEXmedetomidine COmpared to Morphine-DEXCOM Study). Anesthesiology. 2009;111:1075−84.
32. Shi C, Jin J, Qiao L, et al. Effect of perioperative administration of dexmedetomidine on delirium after cardiac surgery in elderly patients: a double-blinded, multi-center, randomized study. Clin Interv Aging. 2019;14:571−5.
33. Soliman R, Zohry G. The myocardial protective effect of dexmedetomidine in high-risk patients undergoing aortic vascular surgery. Ann Card Anaesth. 2016;19:606−13.
34. Zi J, Fan Y, Dong C, et al. Anxiety Administrated by dexmedetomidine to prevent new-onset of postoperative atrial fibrillation in patients undergoing off-pump coronary artery bypass graft. Int Heart J. 2020;61:263−72.
35. Likhvantsev VV, Landoni G, Grebenchikov OA, et al. Perioperative dexmedetomidine supplement decreases delirium incidence after adult cardiac surgery: a randomized, double-blind, controlled study. J Cardiothorac Vasc Anesth. 2021;35:449−57.
36. Lau G, Wald R, Sladen R, et al. Acute kidney injury in cardiac surgery and cardiac intensive care. Semin Cardiothorac Vasc Anesth. 2015;19:270−87.
37. Lassnigg A, Schmid ER, Hiesmayr M, et al. Impact of minimal increases in serum creatinine on outcome in patients after cardiothoracic surgery: do we have to revise current definitions of acute renal failure? Crit Care Med. 2008;36:1129−37.
38. Brown JR, Shore-Lesserson L, Fox AA, et al. The Society of Thoracic Surgeons/Society of Cardiovascular Anesthesiologists/ American Society of Extracorporeal Technology Clinical Practice Guidelines for the Prevention of Adult Cardiac Surgery-Associated Acute Kidney Injury. J Extra Corpor Technol. 2022;54:267−90.
39. Yu Y, Li C, Zhu S, et al. Diagnosis, pathophysiology, and preventive strategies for cardiac surgery-associated acute kidney injury: a narrative review. Eur J Med Res. 2023;28:45.
40. Peng K, McIlroy DR, Bollen BA, et al. Society of Cardiovascular Anesthesiologists Clinical Practice Update for Management of Acute Kidney Injury Associated with Cardiac Surgery. Anesth Analg. 2022;135:744−56.
41. Ueki M, Kawasaki T, Habe K, et al. The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass. Anaesthesia. 2014;69:693−700.
42. Bao N, Tang B. Organ-protective effects and the underlying mechanism of dexmedetomidine. Mediators Inflamm. 2020; 2020:6136105.
43. Singh D, Jagannath S, Priye S, et al. The comparison of dexmedetomidine, esmolol, and combination of dexmedetomidine with esmolol for attenuation of sympathomimetic response to laryngoscopy and intubation in patients undergoing coronary artery bypass grafting. Ann Card Anaesth. 2019;22:353−7.
44. Liu X, Rabin PL, Yuan Y, et al. Effects of anesthetic and sedative agents on sympathetic nerve activity. Heart Rhythm. 2019;16:1875−82. 2019/06/30. DOI: 10.1016.
45. Yang SJ, Fan CN, Wang MJ, et al. Effects of dexmedetomidine on renal microcirculation in ischemia/reperfusion-induced acute kidney injury in rats. Sci Rep. 2021;11:2026.
46. Honore PM, De Bels D, Preseau T, Spapen HD. Dexmedetomidine: the first new kid on the block for preventing cardiac surgery-associated acute kidney injury? Crit Care. 2018;22:151.
47. Li S, Fu S, Xiao Y, Xu G. Recent Perioperative Pharmacological Prevention of Acute Kidney Injury after Cardiac Surgery: A Narrative Review [published correction appears in Am J Cardiovasc Drugs. 2018 Feb 26] Am J Cardiovasc Drugs. 2017;17:17−25.
48. Wu S, Yao H, Cheng N, Guo N, Chen J, Ge M, Cai J. Determining whether dexmedetomidine provides a reno-protective effect in patients receiving laparoscopic radical prostatectomy: a pilot study. Int Urol Nephrol. 2019;51:1553−61.
49. Wu F, Duan H, Xie Y. Preventive effects of dexmedetomidine on renal dysfunction and hemodynamic stability in malignant obstructive jaundice patients during peri-operative period. Med Sci Monit. 2019;25:6782−7.
50. Soh S, Shim JK, Song JW, Bae JC, Kwak YL. Effect of dexmedetomidine on acute kidney injury after aortic surgery: a single-centre, placebo-controlled, randomised controlled trial. Br J Anaesth. 2020. https://doi.org/10.1016/j.bja.2019.12.036. Online ahead of print.
51. Bayram A, Ulgey A, Baykan A, Narin N, Narin F, Esmaoglu A, Boyaci A. The effects of dexmedetomidine on early stage renal functions in pediatric patients undergoing cardiac angiography using non-ionic contrast media: a double-blind, randomized clinical trial. Paediatr Anaesth. 2014;24:426−32.
52. Ostermann M, Kunst G, Baker E, Weerapolchai K, Lumlertgul N. Cardiac Surgery Associated AKI Prevention Strategies and Medical Treatment for CSA-AKI. J Clin Med. 2021;10:5285.
53. Massoth C, Zarbock A, Meersch M. Acute Kidney Injury in Cardiac Surgery. Crit Care Clin. 2021;37:267−78.
54. Kullmar M, Zarbock A, Engelman DT, Chatterjee S, Wagner NM. € Prevention of acute kidney injury. Crit Care Clin. 2020;36:691 −704.
55. Zeng X, McMahon GM, Brunelli SM, Bates DW, Waikar SS. Incidence, outcomes, and comparisons across definitions of AKI in hospitalized individuals. Clin J Am Soc Nephrol. 2014;9:12−20.
56. Koeze J, Keus F, Dieperink W, van der Horst IC, Zijlstra JG, van Meurs M. Incidence, timing and outcome of AKI in critically ill patients varies with the definition used and the addition of urine output criteria. BMC Nephrol. 2017;18:70.
Submetido em:
12/01/2023
Aceito em:
03/07/2023
Facebook
Google+
Twitter
LinkedIn
Mendeley
StumbleUpon
CiteULike
Reddit
Email