Use of dexmedetomidine for prophylactic analgesia and sedation in delayed extubation patients after craniotomy: a study protocol and statistical analysis plan for a randomized controlled trial.
BACKGROUND
Pain and agitation are common in patients after craniotomy. They can result in tachycardia, hypertension, immunosuppression, increased catecholamine production and increased oxygen consumption. Dexmedetomidine, an alpha-2 agonist, provides adequate sedation without respiratory depression, while facilitating frequent neurological evaluation.


METHODS
The study is a prospective, randomized, double-blind, controlled, parallel-group design. Consecutive patients are randomly assigned to one of the two treatment study groups, labeled 'Dex group' or 'Saline group.' Dexmedetomidine group patients receive a continuous infusion of 0.6 μg/kg/h (10 ug/ml). Placebo group patients receive a maintenance infusion of 0.9% sodium chloride for injection at a volume and rate equal to that of dexmedetomidine. The mean percentages of time in optimal sedation, vital signs, various and adverse events, the percentage of patients requiring propofol for rescue to achieve/maintain targeted sedation (Sedation-Agitation Scale, SAS 3 to 4) and total dose of propofol required throughout the study drug infusion are collected. The percentage of patients requiring fentanyl for additional rescue to analgesia and total dose of fentanyl required are recorded. The effects of dexmedetomidine on hemodynamic and recovery responses during extubation are measured. Intensive care unit and hospital length of stay also are collected. Plasma levels of epinephrine, norepinephrine, dopamine, cortisol, neuron-specific enolase and S100-B are measured before infusion (T1), at two hours (T2), four hours (T3) and eight hours (T4) after infusion and at the end of infusion (T5) in 20 patients in each group.


CONCLUSIONS
The study has been initiated as planned in July 2012. One interim analysis advised continuation of the trial. The study will be completed in July 2013.


BACKGROUND
ClinicalTrials (NCT): ChiCTR-PRC-12002903.
Li-Hong
LH
Zhao
Zhong-Hua
ZH
Shi
Ning-Ning
NN
Yin
Jian-Xin
JX
Zhou
D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D060666:Airway Extubation; D018712:Analgesics, Non-Narcotic / Q000009:adverse effects / Q000627:therapeutic use*; D000701:Analgesics, Opioid / Q000627:therapeutic use; D002681:China; D002985:Clinical Protocols; D003399:Craniotomy / Q000009:adverse effects*; D003627:Data Interpretation, Statistical; D020927:Dexmedetomidine / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005283:Fentanyl / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects / Q000627:therapeutic use*; D007902:Length of Stay; D015233:Models, Statistical; D008991:Monitoring, Physiologic; D010147:Pain Measurement; D010149:Postoperative Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D012107:Research Design / Q000706:statistics & numerical data*; D013997:Time Factors; D016896:Treatment Outcome
D058647:Adrenergic alpha-2 Receptor Agonists; D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine; D005283:Fentanyl