DEXmedetomidine for Postoperative Analgesia and Delirium Prevention After NEUROsurgery (DEX-NEURO Trial)

Official title

DEXmedetomidine for Postoperative Analgesia and Delirium Prevention After NEUROsurgery: A Double-blinded Randomised Placebo-controlled Trial (DEX-NEURO Trial)

Overview

Post-craniotomy pain is common and often undertreated. Inadequate analgesia can lead to patient discomfort and higher opioid consumption, which may result in respiratory depression, sedation risks and impaired neurological assessment in the early postoperative period. The incidence of post-operative delirium after intracranial surgery was 19%, ranging from 12 to 26% caused by variation in clinical features and delirium assessment methods1. It is associated with increased morbidity, longer length of hospital stay, and harm to self or staffs. Dexmedetomidine (Precedex) is a highly selective α2-adrenergic agonist with the properties of analgesia, sedative, anxiolytic and neuroprotection without significant respiratory depression. Most of the trials administered a loading dose of 0.5-1.0 μg/kg intravenous dexmedetomidine over 10 minutes followed by infusion dose 0.2-0.7 μg/kg/hour. The use of intraoperative dexmedetomidine is believed to reduce the usage of postoperative opioids where frequent neurological assessment is often required in neurosurgical patients. Beyond the benefit of analgesia, perioperative dexmedetomidine has been studied for prevention of postoperative delirium. Randomized trials in mixed noncardiac surgical populations reported that low-dose perioperative dexmedetomidine may reduce the incidence of delirium. Dexmedetomidine produces dose-dependent bradycardia and hypotension, which should be carefully monitored to maintain the cerebral perfusion pressure in brain surgery. However, most trials and meta-analyses have focused on general surgical or cardiac cohorts; the evidence remains limited in neurosurgical (craniotomy) patients. Although it showed promising benefits of analgesia and neuroprotection in non-neurosurgical patients, recent meta-analyses of intraoperative dexmedetomidine reported high degree of heterogeneity due to the inclusion of varied procedures (elective vs emergent craniotomy), dosing regimes (loading dose only versus loading dose + infusion versus infusion only) and varied primary endpoints (postoperative pain scores, cumulative opioid consumption or incidence of delirium). Therefore, this randomized, double-blind, placebo-controlled trial is designed to examine the use of intravenous dexmedetomidine in the reduction of postoperative pain score and delirium in neurosurgical patients. We hypothesised that intravenous dexmedetomidine reduces postoperative pain score and delirium with lower need of rescue analgesia and amount of morphine consumption in patients undergoing craniotomy.

Detailed description

There are several similar studies been conducted in the literature search. However, the majority of the studies focus on the intensive care unit patient or non-neurosurgery patients. It is believed that intravenous dexmedetomidine can reduce the postoperative pain score with lesser need for rescue analgesia and morphine consumption to facilitate postoperative neurological assessment.

Interventions

• Drug Dexmedetomidine
  intravenous dexmedetomidine loading dose 0.5mcg/kg followed by 0.5mcg/kg/hour
• Drug Normal Saline (0.9% NaCl)
  Intravenous normal saline loading and infusion dose of normal saline

Primary outcome measures

• Postoperative pain score at recovery area [Time frame: In the recovery area after pushing out from the operation theatre (Post-operative 1-hour, Day 1, Day 2)]

Secondary outcome measures (6)

• Need of rescue analgesia [Time frame: In the recovery area after pushing out from operation theatre (Post-operative 1-hour)]
• Total usage of postoperative morphine use in the first 24-hour [Time frame: In the first 24-hour after surgery in neurointensive care unit]
• Postoperative nausea or vomiting [Time frame: Within the first 24-hour in neurointensive care unit]
• Incidence of delirium [Time frame: Day-1 and Day-2 in neurointensive care unit]
• Patient satisfaction scale of analgesia control [Time frame: Day-1 in neurointensive care unit]
• Adverse events of dexmedetomidine (hypotension and bradycardia). [Time frame: During surgery when intravenous dexmedetomidine is started]

Eligibility criteria

Inclusion criteria

• All adult (American Society of Anaesthesiologists (ASA 1-2) who >18 years old and <65 years old undergoing elective craniotomy

Exclusion criteria

• Patients who are ASA 3-5 or BMI <18/ >40 or allergic to dexmedetomidine will be excluded. Patients with high-grade heart block or uncontrolled bradyarrhythmia will also be excluded.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Su X, Meng ZT, Wu XH, Cui F, Li HL, Wang DX, Zhu X, Zhu SN, Maze M, Ma D. Dexmedetomidine for prevention of delirium in elderly patients after non-cardiac surgery: a randomised, double-blind, placebo-controlled trial. Lancet. 2016 Oct 15;388(10054):1893-1902. doi: 10.1016/S0140-6736(16)30580-3. Epub 2016 Aug 16. PMID 27542303
• Zhao LH, Shi ZH, Chen GQ, Yin NN, Chen H, Yuan Y, Cao W, Xu M, Hao JJ, Zhou JX. Use of Dexmedetomidine for Prophylactic Analgesia and Sedation in Patients With Delayed Extubation After Craniotomy: A Randomized Controlled Trial. J Neurosurg Anesthesiol. 2017 Apr;29(2):132-139. doi: 10.1097/ANA.0000000000000260. PMID 26641648
• Bielka K, Kuchyn I, Babych V, Martycshenko K, Inozemtsev O. Dexmedetomidine infusion as an analgesic adjuvant during laparoscopic small es, Cyrillicholecystectomy: a randomized controlled study. BMC Anesthesiol. 2018 Apr 20;18(1):44. doi: 10.1186/s12871-018-0508-6. PMID 29678158
• Li X, Yang J, Nie XL, Zhang Y, Li XY, Li LH, Wang DX, Ma D. Impact of dexmedetomidine on the incidence of delirium in elderly patients after cardiac surgery: A randomized controlled trial. PLoS One. 2017 Feb 9;12(2):e0170757. doi: 10.1371/journal.pone.0170757. eCollection 2017. PMID 28182690

Identifiers

NCT: NCT07398066 · 16023

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗