In this pilot retrospective study, the use of dexmedetomidine as a continuous infusion for anesthesia in children with KT was associated with a perioperative higher MAP, compared with anesthesia without this molecule.
This observation does not seem to be related to a different management of hemodynamic support between the 2 groups. Indeed, we observed no differences regarding quantities of vascular filling solutions or vasopressor supports used intraoperatively. On the other hand, we found no significant difference about HR, even though dexmedetomidine is known to have a bradycardic effect [14].
Moreover, postoperatively, we noticed that patients in the DEX group did not receive more vascular fillings than their counterparts, nor did they require more vasoactive amines. So, we did not observe any delay in intraoperative filling due to the molecule’s hypertensive effect at high doses [14].
In addition, it seems that patients in the DEX group have a more rapid graft function recovery, illustrated by a greater decrease in postoperative creatinine levels compared with the preoperative baseline, and this, from the first postoperative hour to day 7 of management. In the same way, day 1, day 2, first-week and first-month GFR were also higher in the DEX group.
Although the design of this study does not allow us to conclude a causal relationship between dexmedetomidine use and graft function recovery, this finding is nonetheless encouraging, given the rich literature establishing the link between post-transplant serum creatinine and the risk of graft loss. Indeed, in a 1997 study of 510 aKTR from deceased donors, a slow decline in creatinine levels in the first few hours post-transplant was associated with a greater than 10% increased risk of acute graft rejection [15]. Other teams have demonstrated, in large cohorts of adult patients, the predictive character of creatinine levels at one month [16], six months, one year [17] and of the delta of creatinine between six months and one year [18] on long-term graft survival. Similarly, a study about 6686 children concluded to a higher risk of graft loss at 3 years – with a cumulative risk of around 13M per year – if creatinine clearance was < 50ml/min at one month [19]. It therefore seems important to us to explore longer-term creatinine levels in our patients, given the clinical impact that such a difference might implies.
Recently, studies on dexmedetomidine have multiplied in many medical fields. In the context of nephroprotection, this molecule appears to have pharmacological worthy of attention. Firstly, its hemodynamic stabilizing effect could improve local tissue perfusion [1–3] and limit fibrotic ischemia-reperfusion lesions in transplanted organs [4, 5, 20–27]. What’s more, dexmedetomidine might inhibits renin secretion, increasing glomerular filtration and thus kidney excretion of water and sodium [4, 5]. Finally, its stimulatory action on the parasympathetic system could confer beneficial anti-inflammatory properties in the peri-surgical context [28].
The latest available clinical studies show conflicting results in adult patients, with, for example, no significant difference in creatinine clearance after coronary artery bypass surgery [29] and in the occurrence of postoperative Acute Kidney Injury (AKI) after lung cancer surgery [30]. Other authors have noted a reduction in post-operative creatinine levels on day 2 of kidney transplantation, but not on day 7 [31], a lower incidence of DGF [11], and less AKI after non-cardiac surgery [32], cardiac surgery [8] or pediatric cardiac surgery [33]. In a more nuanced way, a recent meta-analysis found no dexmedetomidine-related difference in DGF and acute graft rejection, but a trend towards a more rapid reduction in serum creatinine and urea [34].
To our knowledge, there are no pediatric studies related to dexmedetomidine in renal transplantation, and the main evaluation criteria used differ from one author to another. This is why our study sheds new light on the subject, and presents encouraging results for the use of dexmedetomidine in pediatric renal transplantation.
Lastly, despite the fact that this drug is available in pediatrics without a marketing authorization (MA), numerous studies insist on its [35–39]. It therefore seems reasonable to use it more widely in children.
However, our groups are not entirely comparable on major prognostic criteria for recovery of function [40]: we observed significantly more living donor transplants in DEX group which may lead to confounding bias, particularly in relation to shorter duration of cold ischemia.
Otherwise, this result supports several studies in adult kidney transplant recipient (aKTR) on the influence of intraoperative hemodynamic, and in particular of high MAP, on reducing the risk of DGF [41, 42].
The retrospective, single-center nature of our study and its small sample size mean that it is subject to several biases. In particular, a predictive factor of DGF, such as the difference in size between donors and recipients, could not - for lack of data - be taken into account [43]. Although there was no significant difference at a statistical level, the DEX group included younger patients and more who had benefited from a pre-emptive living-donor transplant than in the no-DEX group. This constitutes a set of good prognostic factors that may have influenced our results on graft function recovery. Moreover, as the patients were not randomized, the use of dexmedetomidine during transplantation was left to the choice of the anesthesiologist, as were the dose infused and other substances delivered during anesthesia. We can also mention the difference in the number of patients on dialysis before transplantation in the two groups, which could distort the interpretation of pre-operative blood volume and serum creatinine in the case of a concomitant dialysis session on the day of transplantation.
Furthermore, in contrast to findings in adults, intraoperative arterial hypotension appears to be less associated with the occurrence of postoperative renal injury in children [44, 45]. However, no studies specific to pediatric renal transplantation have been carried out to date, and recent studies have focused only on AKI to define the renal impact of hypotension. Moreover, in both anesthesia and intensive care, there is little consensus on the pediatric definition of hypotension, whether for systolic, mean or diastolic values. The most widely used seems to be that of the European Resuscitation Council (ERC) recommendations of 2021 [46]. But other definitions have been proposed in recent studies [47, 48], although anesthetic practices in France have not been standardized in the field of kidney transplantation [12].
In conclusion, this preliminary study suggests that the use of intraoperative dexmedetomidine in pediatric renal transplantation provide higher perioperative MAP compared to use of other sedative agents. It may promote better recovery of graft function. These initial findings would need to be confirmed by a multicenter randomized controlled trial before new recommendations in this field could be considered.