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

Trials

Jian-Xin Zhou¹  Ning-Ning Yin¹  Zhong-Hua Shi¹  Li-Hong Zhao¹ 

[1] Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, No 6, Tiantan Xili, Dongcheng district, Beijing 100050, China

关键词: Craniotomy;    Delayed extubation;    Prophylactic;    Sedation;    Analgesia;    Dexmedetomidine;   

Others  :  1093259
DOI  :  10.1186/1745-6215-14-251

 received in 2013-06-11, accepted in 2013-08-07,  发布年份 2013

【 摘 要 】

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/design

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.

Discussion

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.

Trial registration

ClinicalTrials (NCT): ChiCTR-PRC-12002903.

【 授权许可】

   
2013 Zhao et al.; licensee BioMed Central Ltd.

【 参考文献 】

• [1]Nemergut EC, Durieux ME, Missaghi NB, Himmelseher S: Pain management after craniotomy. Best Pract Res Clin Anaesthesiol 2007, 21:557-573.
• [2]Mordhorst C, Latz B, Kerz T, Wisser G, Schmidt A, Schneider A, Jahn-Eimermacher A, Werner C, Engelhard K: Prospective assessment of postoperative pain after craniotomy. J Neurosurg Anesthesiol 2010, 22:202-206.
• [3]De Benedittis G, Lorenzetti A, Migliore M, Spagnoli D, Tiberio F, Villani RM: Postoperative pain in neurosurgery: a pilot study in brain surgery. Neurosurgery 1996, 38:466-469.
• [4]Quiney N, Cooper R, Stoneham M, Walters F: Pain after craniotomy. A time for reappraisal? Br J Neurosurg 1996, 10:295-299.
• [5]Klimek M, Ubben JF, Ammann J, Borner U, Klein J, Verbrugge SJ: Pain in neurosurgically treated patients: a prospective observational study. J Neurosurg 2006, 104:350-359.
• [6]Thibault M, Girard F, Moumdjian R, Chouinard P, Boudreault D, Ruel M: Craniotomy site influences postoperative pain following neurosurgical procedures: a retrospective study. Can J Anaesth 2007, 54:544-548.
• [7]Gottschalk A, Berkow LC, Stevens RD, Mirski M, Thompson RE, White ED, Weingart JD, Long DM, Yaster M: Prospective evaluation of pain and analgesic use following major elective intracranial surgery. J Neurosurg 2007, 106:210-216.
• [8]Fraser GL, Prato BS, Riker RR, Berthiaume D, Wilkins ML: Frequency, severity, and treatment of agitation in young versus elderly patients in the ICU. Pharmacotherapy 2000, 20:75-82.
• [9]Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, Davidson JE, Devlin JW, Kress JP, Joffe AM, Coursin DB, Herr DL, Tung A, Robinson BR, Fontaine DK, Ramsay MA, Riker RR, Sessler CN, Pun B, Skrobik Y, Jaeschke R, American College of Critical Care Medicine: Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med 2013, 41:263-306.
• [10]Gehlbach BK, Kress JP: Sedation in the intensive care unit. Curr Opin Crit Care 2002, 8:290-298.
• [11]Epstein J, Breslow MJ: The stress response of critical illness. Crit Care Clin 1999, 15:17-33.
• [12]Basali A, Mascha EJ, Kalfas I, Schubert A: Relation between perioperative hypertension and intracranial hemorrhage after craniotomy. Anesthesiology 2000, 93:48-54.
• [13]Beretta L, De Vitis A, Grandi E: Sedation in neurocritical patients: is it useful? Minerva Anestesiol 2011, 77:828-834.
• [14]Jacobi J, Fraser GL, Coursin DB, Riker RR, Fontaine D, Wittbrodt ET, Chalfin DB, Masica MF, Bjerke HS, Coplin WM, Crippen DW, Fuchs BD, Kelleher RM, Marik PE, Nasraway SA Jr, Murray MJ, Peruzzi WT, Lumb PD, Task Force of the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM), American Society of Health-System Pharmacists (ASHP), American College of Chest Physicians: Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002, 30:119-141.
• [15]Bekker A, Sturaitis MK: Dexmedetomidine for neurological surgery. Neurosurgery 2005, 57(Suppl 1):1-10.
• [16]Prielipp RC, Wall MH, Tobin JR, Groban L, Cannon MA, Fahey FH, Gage HD, Stump DA, James RL, Bennett J, Butterworth J: Dexmedetomidine-induced sedation in volunteers decreases regional and global cerebral blood flow. Anesth Analg 2002, 95:1052-1059.
• [17]Gerlach AT, Dasta JF: Dexmedetomidine: an updated review. Ann Pharmacother 2007, 41:245-254.
• [18]Venn RM, Hell J, Grounds RM: Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care 2000, 4:302-308. BioMed Central Full Text
• [19]Venn RM, Bradshaw CJ, Spencer R, Realey D, Caudwell E, Naughton C, Vedio A, Singer M, Feneck R, Treacher D, Willatts SM, Grounds RM: Preliminary UK experience of dexmedetomidine, a novel agent for postoperative sedation in the intensive care unit. Anaesthesia 1999, 54:1136-1142.
• [20]Huupponen E, Maksimow A, Lapinlampi P, Särkelä M, Saastamoinen A, Snapir A, Scheinin H, Scheinin M, Meriläinen P, Himanen SL, Jääskeläinen S: Electroencephalogram spindle activity during dexmedetomidine sedation and physiological sleep. Acta Anaesthesiol Scand 2008, 52:289-294.
• [21]Fairbanks CA, Stone LS, Kitto KF: Alpha-2c adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy. J Pharmacol Exp Ther 2002, 300:282-290.
• [22]Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, Heard S, Cheung A, Son SL, Kallio A: The haemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000, 90:834-839.
• [23]Nelson LE, Lu J, Guo T, Saper CB, Franks NP, Maze M: The alpha 2-adrenoceptor agonist dexmedetomidine converges on an endogenous sleep-promoting pathway to exert its sedative effects. Anesthesiology 2003, 98:428-436.
• [24]Ebert TJ, Hall JE, Barney JA, Uhrich TD, Colinco MD: The effects of increasing plasma concentrations of dexmedetomidine in humans. Anesthesiology 2000, 93:382-394.
• [25]Turan G, Ozgultekin A, Turan C, Dincer E, Yuksel G: Advantageous effects of dexmedetomidine on haemodynamic and recovery responses during extubation for intracranial surgery. Eur J Anaesthesiol 2008, 25:816-820.
• [26]Chrysostomou C, Schmitt CG: Dexmedetomidine: sedation, analgesia and beyond. Expert Opin Drug Metab Toxicol 2008, 4:619-627.
• [27]Bekker AY, Basile J, Gold M, Riles T, Adelman M, Cuff G, Mathew JP, Goldberg JD: Dexmedetomidine for awake carotid endarterectomy: efficacy, hemodynamic profile, and side effects. J Neurosurg Anesthesiol 2004, 16:126-135.
• [28]Tan JA, Ho KM: Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis. Intensive Care Med 2010, 36:926-939.
• [29]Soliman RN, Hassan AR, Rashwan AM, Omar AM: Prospective, randomized study to assess the role of dexmedetomidine in patients with supratentorial tumors undergoing craniotomy under general anaesthesia. Middle East J Anesthesiol 2011, 21:325-334.
• [30]Tanskanen P, Kytta J, Randell T, Aantaa R: Dexmedetomidine as an anaesthetic adjuvant in patients undergoing intracranial tumor surgery: a double-blind, randomized and placebo-controlled study. Br J Anaesth 2006, 97:658-665.
• [31]Weinbroum AA, Ben-Abraham R: Dextromethorphan and dexmedetomidine: new agents for the control of perioperative pain. Eur J Surg 2001, 167:563-569.
• [32]Tobias JD, Berkenbosch JW: Sedation during mechanical ventilation in infants and children: dexmedetomidine versus midazolam. South Med J 2004, 97:451-455.
• [33]Venn RM, Grounds RM: Comparison between dexmedetomidine and propofol for sedation in the intensive care unit: patient and clinician perceptions. Br J Anaesth 2001, 87:684-690.
• [34]Kuhmonen J, Polorny J, Miettinen R, Haapalinna A, Jolkkonen J, Riekkinen P Sr, Sivenius J: Neuroprotective effects of dexmedetomidine in the gerbil hippocampus after transient global ischemia. Anesthesiology 1997, 87:371-377.
• [35]Maier C, Steinberg GK, Sun GH, Zhi GT, Maze M: Neuroprotection by the alpha 2-adrenoreceptor agonist dexmedetomidine in a focal model of cerebral ischemia. Anesthesiology 1993, 79:306-312.
• [36]Hoffman WE, Kochs E, Werner C, Thomas C, Albrecht RF: Dexmedetomidine improves neurologic outcome from incomplete ischemia in the rat. Anesthesiology 1991, 75:328-332.
• [37]Cosar M, Eser O, Fidan H, Sahin O, Buyukbas S, Ela Y, Yagmurca M, Ozen OA: The neuroprotective effect of dexmedetomidine in the hippocampus of rabbits after subarachnoid hemorrhage. Surg Neurol 2009, 71:54-59.
• [38]Eser O, Fidan H, Sahin O, Cosar M, Yaman M, Mollaoglu H, Songur A, Buyukbas S: The influence of dexmedetomidine on ischemic rat hippocampus. Brain Res 2008, 1218:250-256.
• [39]Pleines UE, Morganti-Kossmann MC, Rancan M, Joller H, Trentz O, Kossmann T: S-100 beta reflects the extent of injury and outcome, whereas neuronal specific enolase is a better indicator of neuroinflammation in patients with severe traumatic brain injury. J Neurotrauma 2001, 18:491-498.
• [40]Raabe A, Kopetsch O, Woszczyk A, Lang J, Gerlach R, Zimmermann M, Seifert V: Serum S-100B protein as a molecular marker in severe traumatic brain injury. Restor Neurol Neurosci 2003, 21:159-169.
• [41]Rothoerl RD, Woertgen C, Brawanski A: S-100 serum levels and outcome after severe head injury. Acta Neurochir Suppl 2000, 76:97-100.
• [42]Woertgen C, Rothoerl RD, Brawanski A: Early S-100B serum level correlates to quality of life in patients after severe head injury. Brain Inj 2002, 16:807-816.
• [43]Woertgen C, Rothoerl RD, Metz C, Brawanski A: Comparison of clinical, radiologic, and serum marker as prognostic factors after severe head injury. J Quant Spectrosc Radiat Transf 1999, 47:1126-1130.
• [44]Sanchez-Peña P, Pereira AR, Sourour NA, Biondi A, Lejean L, Colonne C, Boch AL, Al Hawari M, Abdennour L, Puybasset L: S100B as an additional prognostic marker in subarachnoid aneurysmal hemorrhage. Crit Care Med 2008, 36:2267-2273.
• [45]Weiss N, Sanchez-Peña P, Roche S, Beaudeux JL, Colonne C, Coriat P, Puybasset L: Prognosis value of plasma S100B protein levels after subarachnoid aneurysmal hemorrhage. Anesthesiology 2006, 104:658-666.