Attenuate the Stress Response in Laparoscopic Cholecystectomy

Официальное название

Dexmedetomidine Versus Fentanyl-Midazolam Combination to Attenuate the Stress Response in Laparoscopic Cholecystectomy

Обзор

Aims of this study are to compare the effectiveness of dexmedetomidine versus fentanyl-midazolam in attenuating hemodynamic stress response during laparoscopic cholecystectomy (mainly HR). And to assess the recovery profile, the pain and opioid requirements, the sedation profile, and any adverse events during the first 24 hrs postoperatively

Подробное описание

Induction of general anesthesia, direct laryngoscopy and tracheal intubation induce marked cardiovascular changes as well as autonomic reflex activity. Although the responses of blood pressure and heart rate are short lived, they might have detrimental effects in high-risk patients, especially those with cardiovascular disease (1). These cardiovascular responses are associated with increased plasma levels of catecholamines (2). The main reason for the intubation induced hypertension seems to be a release of noradrenaline and, to a lesser extent, of adrenaline. In addition, increased levels of adrenocorticotrophic hormone (ACTH) and dopamine have also been reported (3).

A variety of factors have been shown to have an effect on this stress response: the choice and dosages of premedication and induction agents (4), the skill of the operator, and probably the technique being used. Numerous studies have demonstrated an increased stress response during direct laryngoscopy, fibreoptic intubation and insertion of the laryngeal mask (5).

* Dexmedetomidine is an Alpha 2 adrenoreceptors agonists may exert its analgesic effect through hyperpolarization of the non-adrenergic neurons which leads to depression of neuronal firing in the locus ceruleous together with suppression of the release of norepinephrine because of the stimulation of the central adrenergic receptors which produces a hypnotic effect without ventilatory depression (6). * Midazolam is the benzodiazepine with the shortest half-life. It produces sedation and amnesia by acting on the γ-aminobutyric acid type-A receptors; additionally, its combined application in peripheral nerve blocks can increase the convulsive threshold of local anesthetics. It should be noted that GABA enhanced in amplitude by midazolam resulting in inhabitation of projection neurons and antinociception (7).

Fentanyl citrate is an opioid strong analgesic that is particularly well suited for use in anesthesia because of its high potency, rapid onset and short duration of action, absence of emetic activity, and minimal hypotensive activity after intravenous administration. As with other morphine-like analgesics. (8).

Laparoscopic cholecystectomy has increasingly been accepted as the procedure of choice for treatment of symptomatic gallstones and chronic cholecystitis (9). Its role and its timing in the management of acute cholecystitis, however remain controversial. The potential hazard of severe complications as a result of distorted anatomy caused by acute inflammation is a major concern (10)

Вмешательства

• Препарат Dexmedetomidine
  investigator will give Loading dose 1 mcg/kg IV over 10 min, followed by infusion 0.5 mcg/kg/h until pneumoperitoneum established
• Препарат Fentanyl- midazolam
  Investigator will inject Fentanyl 2 mcg/kg IV + Midazolam 0.05 mg/kg IV before induction.

Первичные конечные точки

• Hemodynamics [Срок оценки: During procedure]

Критерии участия

Критерии включения

• Age 18-65 years.
• Both sexes.
• American Society of Anesthesiology (ASA) physical status I - II.

Критерии исключения

• Known allergy to study drugs.
• Uncontrolled, non-correctable comorbidities (hepatic, renal or cardiac such as hypertension \& Arrhythmia ).
• History of psychiatric illness or substance abuse.
• Pregnancy or lactation

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Публикации

• Kum CK, Goh PM, Isaac JR, Tekant Y, Ngoi SS. Laparoscopic cholecystectomy for acute cholecystitis. Br J Surg. 1994 Nov;81(11):1651-4. doi: 10.1002/bjs.1800811130. PMID 7827896
• Bass EB, Pitt HA, Lillemoe KD. Cost-effectiveness of laparoscopic cholecystectomy versus open cholecystectomy. Am J Surg. 1993 Apr;165(4):466-71. doi: 10.1016/s0002-9610(05)80942-0. PMID 8480883
• GARDOCKI JF, YELNOSKY J. A STUDY OF SOME OF THE PHARMACOLOGIC ACTIONS OF FENTANYL CITRATE. Toxicol Appl Pharmacol. 1964 Jan;6:48-62. doi: 10.1016/0041-008x(64)90021-3. No abstract available. PMID 14105897
• Kohno T, Kumamoto E, Baba H, Ataka T, Okamoto M, Shimoji K, Yoshimura M. Actions of midazolam on GABAergic transmission in substantia gelatinosa neurons of adult rat spinal cord slices. Anesthesiology. 2000 Feb;92(2):507-15. doi: 10.1097/00000542-200002000-00034. PMID 10691239
• Kosugi T, Mizuta K, Fujita T, Nakashima M, Kumamoto E. High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without alpha(2) adrenoceptor activation. Br J Pharmacol. 2010 Aug;160(7):1662-76. doi: 10.1111/j.1476-5381.2010.00833.x. PMID 20649570
• Smith JE, King MJ, Yanny HF, Pottinger KA, Pomirska MB. Effect of fentanyl on the circulatory responses to orotracheal fibreoptic intubation. Anaesthesia. 1992 Jan;47(1):20-3. doi: 10.1111/j.1365-2044.1992.tb01946.x. PMID 1536396
• Bucx MJ, van Geel RT, Scheck PA, Stijnen T. Cardiovascular effects of forces applied during laryngoscopy. The importance of tracheal intubation. Anaesthesia. 1992 Dec;47(12):1029-33. doi: 10.1111/j.1365-2044.1992.tb04195.x. PMID 1489023
• Weatherill D, Spence AA. Anaesthesia and disorders of the adrenal cortex. Br J Anaesth. 1984 Jul;56(7):741-9. doi: 10.1093/bja/56.7.741. No abstract available. PMID 6375706

Идентификаторы

NCT: NCT07425444 · stress in lap cholecystectomy

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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