Pharmacokinetics of dexmedetomidine administered to patients with end-stage renal failure and secondary hyperparathyroidism undergoing general anaesthesia

Zhong, Wu; Zhang, Y.; Zhang, M.-Z.; Huang, Xiaohui; Li, Y.; Li, R.; Liu, Qi

doi:10.1111/jcpt.12652

Cited by 12 publications

(6 citation statements)

References 22 publications

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“…It is metabolised by glucuronidation and CYP2A6 hydroxylation and subsequently excreted in urine almost exclusively as metabolite [2]. Its pharmacokinetics has been described by a two-compartmental model both in adults [3][4][5][6][7] and children [8][9][10][11][12]. Still, other investigators have also reported the disposition of dexmedetomidine according to one-compartment [13] and three-compartment [14][15][16] models.…”

Section: Introductionmentioning

confidence: 99%

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation

Dijkman

Cock

Smets

et al. 2019

Eur J Clin Pharmacol

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Purpose There is a need for alternative analgosedatives such as dexmedetomidine in neonates. Given the ethical and practical difficulties, protocol design for clinical trials in neonates should be carefully considered before implementation. Our objective was to identify a protocol design suitable for subsequent evaluation of the dosing requirements for dexmedetomidine in mechanically ventilated neonates. Methods A published paediatric pharmacokinetic model was used to derive the dosing regimen for dexmedetomidine in a firstin-neonate study. Optimality criteria were applied to optimise the blood sampling schedule. The impact of sampling schedule optimisation on model parameter estimation was assessed by simulation and re-estimation procedures for different simulation scenarios. The optimised schedule was then implemented in a neonatal pilot study. Results Parameter estimates were more precise and similarly accurate in the optimised scenarios, as compared to empirical sampling (normalised root mean square error: 1673.1% vs. 13,229.4% and relative error: 46.4% vs. 9.1%). Most importantly, protocol deviations from the optimal design still allowed reasonable parameter estimation. Data analysis from the pilot group (n = 6) confirmed the adequacy of the optimised trial protocol. Dexmedetomidine pharmacokinetics in term neonates was scaled using allometry and maturation, but results showed a 20% higher clearance in this population compared to initial estimates obtained by extrapolation from a slightly older paediatric population. Clearance for a typical neonate, with a post-menstrual age (PMA) of 40 weeks and weight 3.4 kg, was 2.92 L/h. Extension of the study with 11 additional subjects showed a further increased clearance in pre-term subjects with lower PMA. Conclusions The use of optimal design in conjunction with simulation scenarios improved the accuracy and precision of the estimates of the parameters of interest, taking into account protocol deviations, which are often unavoidable in this event-prone population.

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Section: Introductionmentioning

confidence: 99%

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation

Dijkman

Cock

Smets

et al. 2019

Eur J Clin Pharmacol

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“…The efficacy of α-2 agonists specifically in RSS has been reported, but only in case reports so far ( 36 , 37 ). We chose dexmedetomidine over clonidine because it has many advantages: it is approved for sedation of critically ill patients, and has a short half-life without alteration in patients with impaired renal function ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study)

Dargent

Bourredjem²,

Argaud³

et al. 2022

Front. Med.

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IntroductionRefractory septic shock (RSS) is characterized by high vasopressor requirements, as a consequence of vasopressor resistance, which may be caused or enhanced by sympathetic hyperactivation. Experimental models and clinical trials show a reduction in vasopressor requirements and improved microcirculation compared to conventional sedation. Dexmedetomidine did not reduce mortality in clinical trials, but few septic shock patients were enrolled. This pilot trial aims to evaluate vasopressor re-sensitization with dexmedetomidine and assess the effect size, in order to design a larger trial.MethodsThis is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled trial, comparing dexmedetomidine versus placebo in RSS patients with norepinephrine dose ≥0.5μg/kg/min. The primary outcome is blood pressure response to phenylephrine challenge, 6 hours after completion of a first challenge, after study treatment initiation. Secondary outcomes include feasibility and safety outcomes (bradycardia), mortality, vasopressor requirements, heart rate variability, plasma and urine catecholamines levels. The sample size is estimated at 32 patients to show a 20% improvement in blood pressure response to phenylephrine. Randomization (1:1) will be stratified by center, sedation type and presence of liver cirrhosis. Blood pressure and ECG will be continuously recorded for the first 24 h, enabling high-quality data collection for the primary and secondary endpoints. The study was approved by the ethics committee “Sud-Est VI” (2019-000726-22) and patients will be included after informed consent.DiscussionThe present study will be the first randomized trial to specifically address the hemodynamic effects of dexmedetomidine in patients with septic shock. We implement a high-quality process for data acquisition and recording in the first 24 h, ensuring maximal quality for the evaluation of both efficacy and safety outcomes, as well as transparency of results. The results of the study will be used to elaborate a full-scale randomized controlled trial with mortality as primary outcome in RSS patients.Trial registrationRegistered with ClinicalTrials.gov (NCT03953677). Registered 16 May 2019, https://clinicaltrials.gov/ct2/show/NCT03953677.

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“…DEX was administered to maintain sedation during the operation because its pharmacokinetic parameters in patients with end-stage renal failure are similar to those in patients with normal renal function. 30 More importantly, it has no adverse effect on kidney function. We used tramadol as rescue analgesia for postoperative analgesia insufficiency because nonsteroidal drugs are inappropriate for these patients, and potent opioids are not necessary because of the small incision.…”

Section: Discussionmentioning

confidence: 99%

<p>Ultrasound-Guided Unilateral Transversus Abdominis Plane Combined with Rectus Sheath Block versus Subarachnoid Anesthesia in Patients Undergoing Peritoneal Dialysis Catheter Surgery: A Randomized Prospective Controlled Trial</p>

Guo

Zhao

et al. 2020

JPR

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Background Peritoneal dialysis catheter placement can be performed under general anesthesia, local anesthesia or subarachnoid anesthesia (SA). Recently, studies have reported the successful placement of peritoneal dialysis catheters using a transversus abdominis plane (TAP) block and rectus sheath (RS) block. This study compared the TAP + RS block with SA for patients undergoing peritoneal dialysis catheter placement. Methods Sixty patients were randomly divided into two groups, with 30 receiving unilateral ultrasound-guided TAP + RS block anesthesia and 30 receiving SA. The demographic characteristics, anesthesia efficacy, indicators related to anesthesia or operation, hemodynamic index, postoperative pain numeric rating score (NRS), postoperative recovery indicators, complications related to anesthesia or surgery, and dosage of sedative or analgesic medication were analyzed. Results Anesthesia operation time was significantly shorter in the TAP + RS block group than in the SA group ( P <0.001), while there was no significant difference in success rates (TAP + RS 93.33% [95% confidence interval, 95% CI, 83.9–102.8%] vs SA 100.00% [95% CI, 100–100%], P =0.472). Two patients in the TAP + RS group needed extra analgesia, although the dermatome pinprick sensation test gave negative results for all patients. Patients who received the TAP + RS block expressed significantly less pain on movement or at rest at 4 h and 8 h postoperative. Fewer patients needed rescue analgesia with tramadol in the postoperative period in the TAP + RS block group than in the SA group ( P <0.05). The intraoperative MAP was more stable ( P <0.05) in the TAP + RS group compared to the SA group. Conclusion The TAP + RS block is a safe, effective method for use as the principal anesthesia technique in PD catheter placement. Compared to SA, it has the advantages of less influence on hemodynamics and a better postoperative analgesic effect.

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Pharmacokinetics of dexmedetomidine administered to patients with end-stage renal failure and secondary hyperparathyroidism undergoing general anaesthesia

Cited by 12 publications

References 22 publications

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation

Dose rationale and pharmacokinetics of dexmedetomidine in mechanically ventilated new-borns: impact of design optimisation

Dexmedetomidine to reduce vasopressor resistance in refractory septic shock: Protocol for a double-blind randomized controlled pilot trial (ADRESS Pilot study)

<p>Ultrasound-Guided Unilateral Transversus Abdominis Plane Combined with Rectus Sheath Block versus Subarachnoid Anesthesia in Patients Undergoing Peritoneal Dialysis Catheter Surgery: A Randomized Prospective Controlled Trial</p>

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