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Effect of intraoperative dexmedetomidine on postoperative delirium after kidney transplantation: a randomised, double-blind, placebo-controlled trial

This randomized, double-blind, placebo-controlled trial demonstrates that intraoperative dexmedetomidine significantly reduces the incidence of postoperative delirium within five days following kidney transplantation without increasing intraoperative hypotension or bradycardia.

Original authors: Haixu Wei, Qing Wen, Weiyi Xu, Huanhuan Xiu, Xinxin Shao, Jianhong Ye, Tao Zhang

Published 2026-10-07

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CC BY 4.0

Original authors: Haixu Wei, Qing Wen, Weiyi Xu, Huanhuan Xiu, Xinxin Shao, Jianhong Ye, Tao Zhang

Original paper licensed under CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). ✨ This is an AI-generated explanation of the paper below. It is not written or endorsed by the authors. For technical accuracy, refer to the original paper. Read full disclaimer

After a major surgery, the human brain can sometimes stumble. A condition known as postoperative delirium causes a sudden, fluctuating confusion where a patient may lose track of time, struggle to pay attention, or feel disoriented. This is not merely a temporary fog; it is a serious complication that can extend hospital stays, increase the risk of readmission, and even lead to long-term cognitive decline. The risk is particularly high for patients receiving kidney transplants. These individuals often arrive at the hospital with a body already stressed by years of kidney failure, carrying imbalances in their blood chemistry and a history of taking multiple medications. This fragile state makes them especially vulnerable to the shock of surgery, with some studies suggesting that up to one in five such patients might develop this confusion after the operation.

For years, doctors have looked for ways to protect the brain during these high-stakes procedures. One promising candidate is a medication called dexmedetomidine. This drug works by gently calming the nervous system, slowing down the body's stress response and helping the brain rest in a state that resembles natural, deep sleep rather than the heavy, groggy sedation caused by other anesthetics. While some research has hinted that this drug could prevent confusion after surgery, other studies have produced mixed results, leaving the medical community unsure if it truly works for everyone or just specific groups. To settle this question for kidney transplant patients, a team of researchers at The First Affiliated Hospital of Sun Yat-sen University in China decided to test the drug directly in a rigorous, controlled setting.

The researchers recruited 180 adults scheduled to receive a new kidney between 2018 and 2021. They designed a study where neither the patients nor the doctors knew who was receiving the real treatment, ensuring that the results would be free from bias. Immediately after the patient was put to sleep and a breathing tube was inserted, the team administered a single dose of the study medication. Half the patients received a small amount of dexmedetomidine, while the other half received a harmless saltwater solution that looked and felt exactly the same. From that point on, both groups received the exact same standard care, including the same pain management and post-surgery monitoring. The team then watched closely for the next five days, checking the patients every twelve hours to see if signs of confusion appeared.

The results were clear and significant. In the group that received the saltwater, nearly 15 percent of the patients developed postoperative delirium. In contrast, the group that received dexmedetomidine saw this rate drop to just 4.5 percent. This means that for every 100 patients treated with the drug, roughly 10 fewer would experience this dangerous confusion compared to those who did not receive it. The researchers calculated that the drug reduced the risk of delirium by about 70 percent. Importantly, the team found no evidence that the drug caused dangerous drops in blood pressure or heart rate, which are known side effects of similar medications when given in high doses. The patients who received the drug remained stable throughout the surgery, suggesting that this protective effect on the brain did not come at the cost of physical safety.

Beyond the brain, the study uncovered an unexpected and intriguing side effect regarding the new kidney itself. Among the patients who received the saltwater, a small number experienced acute rejection, where the body's immune system began to attack the new organ. Remarkably, no patients in the dexmedetomidine group experienced this rejection. While the researchers caution that this finding needs further confirmation because the number of rejection cases was small, it suggests that the drug might offer a secondary benefit by helping the new kidney settle in more peacefully. However, the drug did not speed up the recovery of kidney function in terms of urine output, nor did it shorten the overall time patients spent in the hospital.

The study also looked at how long the confusion lasted in those who did develop it. The duration of delirium was similar in both groups, indicating that while the drug is excellent at preventing the condition from starting, it does not necessarily shorten the episode once it has already taken hold. This distinction is vital: the drug acts as a shield against the onset of confusion rather than a cure for an existing episode. The researchers noted that their study had some limitations, such as being conducted at a single hospital and including relatively few elderly or obese patients, which means the findings might need to be tested in broader populations. Nevertheless, the evidence presented offers a compelling case that a simple, single dose of this calming medication can significantly lower the risk of brain fog for some of the most vulnerable surgical patients, providing a safer path through one of the most critical moments in their medical journey.

Technical Summary: Effect of Intraoperative Dexmedetomidine on Postoperative Delirium After Kidney Transplantation

Problem Statement
Postoperative delirium (POD) is a prevalent and severe central nervous system complication associated with prolonged hospitalization, increased healthcare costs, cognitive decline, and higher mortality. Patients undergoing kidney transplantation are at an elevated risk for POD due to preoperative factors inherent to end-stage renal disease (ESRD), including electrolyte disturbances, polypharmacy, uremic toxin accumulation, and pre-existing cognitive impairment. While dexmedetomidine, a selective $\alpha_2$ -adrenergic receptor agonist, has demonstrated neuroprotective properties and reduced POD incidence in other surgical populations, its efficacy specifically in kidney transplant recipients remains under-investigated. Furthermore, existing literature presents heterogeneous findings regarding dexmedetomidine's preventive efficacy, necessitating targeted evaluation in high-risk, specific surgical cohorts.

Methodology
The study was a prospective, single-centre, randomised, double-blind, placebo-controlled trial conducted at The First Affiliated Hospital of Sun Yat-sen University between January 2018 and December 2021.

Participants: 180 adult patients (aged 18–75) scheduled for allogeneic kidney transplantation were enrolled. Exclusion criteria included significant cardiac conduction abnormalities, severe heart failure, preoperative shock, severe hepatic dysfunction, and a history of severe psychiatric illness or delirium.
Intervention: Participants were randomised (1:1) to receive either a single intravenous bolus of dexmedetomidine (0.4 µg/kg) diluted in 100 mL of normal saline or an equal volume of normal saline (control). Administration occurred immediately after tracheal intubation.
Anesthesia and Management: All patients received standardised combined intravenous–inhalational general anaesthesia. Haemodynamic management aimed to maintain mean arterial pressure (MAP) $\ge$ 80 mmHg and central venous pressure (CVP) at 8–12 mmHg prior to graft reperfusion. Postoperative analgesia was standardised using hydromorphone via patient-controlled analgesia (PCA).
Outcomes:
- Primary Outcome: Incidence of POD within the first 5 postoperative days, assessed every 12 hours using the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) following Richmond Agitation–Sedation Scale (RASS) screening.
- Secondary Outcomes: Duration of POD, acute graft rejection, postoperative urine output, length of hospital stay, intraoperative haemodynamic stability (hypotension and bradycardia), and other postoperative complications.
Statistical Analysis: The primary analysis was a complete-case analysis. Sample size was calculated based on a pilot study, targeting 90 participants per group to account for a 20% dropout rate. Sensitivity analyses were performed excluding participants aged $\ge$ 65 years and those with a BMI $\ge$ 30 kg/m².

Key Results

Primary Outcome (POD Incidence): In the complete-case analysis (174 participants), the incidence of POD was significantly lower in the dexmedetomidine (DEX) group compared to the control (CON) group: 4.5% (4/88) vs. 15.1% (13/86). This corresponds to a risk ratio (RR) of 0.30 (95% CI, 0.10–0.89; $P = 0.019$ ).
Sensitivity Analyses: Excluding participants aged $\ge$ 65 years or those with obesity (BMI $\ge$ 30 kg/m²) yielded consistent results, with the DEX group maintaining a significantly lower incidence of POD (OR 0.22 and 0.27, respectively).
Secondary Outcomes:
- Acute Graft Rejection: No cases of acute graft rejection occurred in the DEX group (0/88), compared to 8.1% (7/86) in the CON group (Fisher's exact $P = 0.006$ ). The authors note this as an exploratory finding due to the small number of events and lack of power for this secondary endpoint.
- Duration of POD: There was no significant difference in the duration of delirium among affected patients between the two groups ( $P = 0.512$ ).
- Haemodynamic Safety: No significant differences were observed between groups regarding intraoperative hypotension (29.5% vs. 31.4%; $P = 0.791$ ) or bradycardia (21.6% vs. 20.9%; $P = 0.915$ ).
- Other Metrics: No significant differences were found in postoperative urine output, length of hospital stay, or other postoperative complications (e.g., delayed graft function, infection).

Significance and Claims
The study concludes that intraoperative administration of dexmedetomidine is associated with a significantly lower incidence of postoperative delirium within the first five days following kidney transplantation, without increasing the risk of intraoperative hypotension or bradycardia. The authors suggest a potential perioperative neuroprotective effect of dexmedetomidine in this high-risk population.

Regarding the observed reduction in acute graft rejection, the authors explicitly state that this finding should be considered exploratory and hypothesis-generating rather than definitive, as the trial was not powered to detect differences in this secondary outcome. Similarly, while dexmedetomidine reduced the incidence of delirium, it did not shorten the duration of delirium once established, suggesting the drug may primarily influence the initiation of delirium-related pathophysiological processes.

The paper acknowledges limitations, including its single-centre design, the potential lack of power for rare outcomes like graft rejection, the short assessment window (5 days) for delirium, and the absence of inflammatory biomarker measurements to confirm mechanistic hypotheses. The authors emphasize that the findings support the safety and efficacy of the specific dosing regimen (0.4 µg/kg bolus) for POD prevention in kidney transplant recipients.

Technical Summary: Effect of Intraoperative Dexmedetomidine on Postoperative Delirium After Kidney Transplantation

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