NIHR DC Discover

NIHR Signal Alternative sedative reduces the risk of acute kidney injury following cardiac surgery

Published on 10 July 2018

doi: 10.3310/signal-000613

The sedative drug dexmedetomidine can reduce the risk of acute kidney injury when given during non-emergency cardiac surgery. Trial participants who received dexmedetomidine were a third less likely to develop acute kidney injury than those receiving placebo or other treatments. There was no difference in mortality or length of hospital stay.

This systematic review identified 10 studies of 1,575 participants. Surgical procedures included coronary artery bypass grafting with or without valve surgery and aortic vascular surgery. Dexmedetomidine was given before or shortly after surgery. Most participants were followed up for the duration of their hospital stay, or for 12 to 30 days. 

Many strategies are currently used to reduce the risk of kidney injury following cardiac surgery. This study provides some evidence that dexmedetomidine may help reduce this risk, but larger trials are needed before it can be routinely recommended.

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Why was this study needed?

Acute kidney injury (AKI) affects 8 to 28% of people after cardiac surgery. It can be life-threatening, and nearly half of those affected require intensive care. It is more likely to occur if there is inadequate blood flow and inflammation. Because of the multifactorial causes, there is no uniform strategy for preventing AKI after cardiac surgery.

Dexmedetomidine is an alpha2-adrenergic agonist with many different effects including sedation, pain relief and reducing inflammation. It can also help maintain the blood flow to the kidneys during surgery.

Animal studies suggest that dexmedetomidine may be protective against AKI, but there is clinical uncertainty as to whether it could reduce AKI rates in adults undergoing cardiac surgery. The researchers, therefore, aimed to investigate whether perioperative dexmedetomidine reduced the risk for AKI and mortality in cardiac surgery.

What did this study do?

This systematic review and meta-analysis identified 10 randomised controlled trials of 1,575 participants involving dexmedetomidine in non-emergency adult cardiac surgery. The primary outcome was AKI, occurring within seven days of cardiac surgery.

Two studies looked solely at coronary artery bypass grafting, seven at combined coronary graft and valve surgery and one at aortic vascular surgery. The studies were from Turkey, Korea, China, Egypt, Australia, Canada and Finland. Most participants were male, and their average age was between 54 and 73 years.

The studies used slightly different scales to define AKI, and some had few participants (range 50 to 299 people). Trials were mostly unclear in the reporting of the risks of bias, which may have led to an overestimation of the effect.

What did it find?

  • Use of dexmedetomidine reduced the risk of AKI by a third. AKI occurred in 68/788 cases (8.6%) in the dexmedetomidine group compared with 97/787 cases (12.3%) in the control group who were given a placebo or alternative drug (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45 to 0.92; 10 studies).
  • There was no statistically significant difference in mortality; 4/487 (0.8%) died in the dexmedetomidine group compared with 11/483 (2.3%) of the control group (OR 0.43, 95% CI 0.14 to 1.28; six studies).
  • There was no difference in time spent on mechanical ventilation (weighted mean difference [WMD] ‑0.22 days, 95% CI ‑2.04 to 1.7), length of time in intensive care (WMD 0.85 days, 95% CI ‑2.14 to 0.45) or length of time in hospital (WMD ‑0.24 days, 95% CI ‑0.71 to 0.23).
  • There were no data on side effects or adverse drug reactions related to dexmedetomidine.

What does current guidance say on this issue?

The NICE 2013 guideline on AKI recommends pre-surgical assessment of risk factors, to inform a clinical management plan. At present, no specific advice is given regarding pharmacological interventions to reduce the risk of kidney injury. There is no plan to update this guideline in the near future.

What are the implications?

Renal protection during cardiac and aortic surgery has been extensively studied. This meta-analysis provides a good foundation for future investigations of a new class of drug in this setting.

The included trials were of variable quality and size and lacked clear conclusions on optimal timing and dosage. Larger trials would help to determine the place of dexmedetomidine in UK clinical practice.

Citation and Funding

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).

This project was funded by the Beijing Shijitan Hospital Youth Funds (grant number 2016-q08).

Bibliography

Coppolino G, Presta P, Saturno L, et al. Acute kidney injury in patients undergoing cardiac surgery. J Nephrol. 2013;26(1):32-40.

NICE. Acute kidney injury: prevention, detection and management. CG169. London: National Institute for Health and Care Excellence; 2013.

Royal College of Anaesthetists. Guidance on the provision of anaesthesia services for cardiac and thoracic procedures 2018. Royal College of Anaesthetists: London; 2018.

Why was this study needed?

Acute kidney injury (AKI) affects 8 to 28% of people after cardiac surgery. It can be life-threatening, and nearly half of those affected require intensive care. It is more likely to occur if there is inadequate blood flow and inflammation. Because of the multifactorial causes, there is no uniform strategy for preventing AKI after cardiac surgery.

Dexmedetomidine is an alpha2-adrenergic agonist with many different effects including sedation, pain relief and reducing inflammation. It can also help maintain the blood flow to the kidneys during surgery.

Animal studies suggest that dexmedetomidine may be protective against AKI, but there is clinical uncertainty as to whether it could reduce AKI rates in adults undergoing cardiac surgery. The researchers, therefore, aimed to investigate whether perioperative dexmedetomidine reduced the risk for AKI and mortality in cardiac surgery.

What did this study do?

This systematic review and meta-analysis identified 10 randomised controlled trials of 1,575 participants involving dexmedetomidine in non-emergency adult cardiac surgery. The primary outcome was AKI, occurring within seven days of cardiac surgery.

Two studies looked solely at coronary artery bypass grafting, seven at combined coronary graft and valve surgery and one at aortic vascular surgery. The studies were from Turkey, Korea, China, Egypt, Australia, Canada and Finland. Most participants were male, and their average age was between 54 and 73 years.

The studies used slightly different scales to define AKI, and some had few participants (range 50 to 299 people). Trials were mostly unclear in the reporting of the risks of bias, which may have led to an overestimation of the effect.

What did it find?

  • Use of dexmedetomidine reduced the risk of AKI by a third. AKI occurred in 68/788 cases (8.6%) in the dexmedetomidine group compared with 97/787 cases (12.3%) in the control group who were given a placebo or alternative drug (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45 to 0.92; 10 studies).
  • There was no statistically significant difference in mortality; 4/487 (0.8%) died in the dexmedetomidine group compared with 11/483 (2.3%) of the control group (OR 0.43, 95% CI 0.14 to 1.28; six studies).
  • There was no difference in time spent on mechanical ventilation (weighted mean difference [WMD] ‑0.22 days, 95% CI ‑2.04 to 1.7), length of time in intensive care (WMD 0.85 days, 95% CI ‑2.14 to 0.45) or length of time in hospital (WMD ‑0.24 days, 95% CI ‑0.71 to 0.23).
  • There were no data on side effects or adverse drug reactions related to dexmedetomidine.

What does current guidance say on this issue?

The NICE 2013 guideline on AKI recommends pre-surgical assessment of risk factors, to inform a clinical management plan. At present, no specific advice is given regarding pharmacological interventions to reduce the risk of kidney injury. There is no plan to update this guideline in the near future.

What are the implications?

Renal protection during cardiac and aortic surgery has been extensively studied. This meta-analysis provides a good foundation for future investigations of a new class of drug in this setting.

The included trials were of variable quality and size and lacked clear conclusions on optimal timing and dosage. Larger trials would help to determine the place of dexmedetomidine in UK clinical practice.

Citation and Funding

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).

This project was funded by the Beijing Shijitan Hospital Youth Funds (grant number 2016-q08).

Bibliography

Coppolino G, Presta P, Saturno L, et al. Acute kidney injury in patients undergoing cardiac surgery. J Nephrol. 2013;26(1):32-40.

NICE. Acute kidney injury: prevention, detection and management. CG169. London: National Institute for Health and Care Excellence; 2013.

Royal College of Anaesthetists. Guidance on the provision of anaesthesia services for cardiac and thoracic procedures 2018. Royal College of Anaesthetists: London; 2018.

Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta-analysis of randomized controlled trials

Published on 18 January 2018

Liu, Y.,Sheng, B.,Wang, S.,Lu, F.,Zhen, J.,Chen, W.

BMC Anesthesiol Volume 18 , 2018

BACKGROUND: Dexmedetomidine has been shown to confer direct renoprotection by stabilizing the sympathetic system, exerting anti-inflammatory effects and attenuating ischemia/reperfusion (I/R) injury in preclinical studies. Results from clinical trials of dexmedetomidine on acute kidney injury (AKI) following adult cardiac surgery are controversial. METHODS: We searched EMBASE, PubMed, and Cochrane CENTRAL databases for randomized controlled trials (RCTs) comparing the renal effect of dexmedetomidine versus placebo or other anesthetic drugs in adult patients undergoing cardiac surgery. The primary outcome was the incidence of AKI. The secondary outcomes were mechanical ventilation (MV) duration, intensive care unit (ICU) stay and hospital length of stay(LOS), and postoperative mortality (in-hospital or within 30 days). RESULTS: Ten trials with a total of 1575 study patients were selected. Compared with controls, dexmedetomidine significantly reduced the incidence of postoperative AKI [68/788 vs 97/787; odds ratio(OR), 0.65; 95% confidence interval (CI), 0.45-0.92; P = 0.02; I(2) = 0.0%], and there was no difference between groups in postoperative mortality (4/487 vs 11/483; OR, 0.43; 95% CI, 0.14-1.28; P = 0.13; I(2) = 0.0%), MV duration [in days; n = 1229; weighted mean difference(WMD), -0.22; 95% CI, -2.04 to 1.70; P = 0.81], ICU stay (in days; n = 1363; WMD, -0.85; 95% CI, -2.14 to 0.45; P = 0.20), and hospital LOS (in days; n = 878; WMD, -0.24; 95% CI, -0.71 to 0.23; P = 0.32). CONCLUSIONS: Perioperative administration of dexmedetomidine in adult patients undergoing cardiac surgery may reduce the incidence of postoperative AKI. Future trials are needed to determine the dose and timing of dexmedetomidine in improving outcomes, especially in patients with decreased baseline kidney function.

Within individual trials, acute kidney injury was defined according to the RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease), AKIN (Acute Kidney Injury Network) or KDIGO (Kidney Disease: Improving Global Outcomes) scales.

Expert commentary

The past decades have seen substantial reductions in the mortality associated with cardiac surgery. However, kidney injury following cardiac surgery is associated with an increased risk of death in the month after surgery and may increase the chances of death in the five years after the operation.

This study suggests that dexmedetomidine may protect the kidneys during surgery.

Dexmedetomidine has other effects, such as lowering the blood pressure and cannot be recommended on the basis of this systematic review alone. However, the results are encouraging and suggest that a large randomised trial would be warranted.

Simon Howell, Senior Lecturer in Anaesthesia, University of Leeds