Remifentanil and Stress Hormones Response

Effect of Different Doses of Remifentanil on Stress Response During Laparoscopic Cholecystectomy

Perioperative adequate analgesia reduces neuroendocrine stress response and postoperative complications. Because opioids are the most effective parenteral drugs to control pain and stress response, in this prospective randomized double-blinded controlled study we supposed that higher dose of remifentanil may reduce stress marker variations compared to lower dose in patients undergoing laparoscopic cholecystectomy.

Study Overview

• Status: Completed
• Conditions: Stress Response
• Intervention / Treatment: Drug: Remifentanil Injectable Product

Detailed Description

Fifty Caucasian patients, aged 20-70 years, with American Society of Anesthesiologist physical status I-II, undergoing laparoscopic cholecystectomy were enrolled. Exclusion criteria were: patient refusal, thyroid disorders, diabetes mellitus, BMI > 30, use of corticosteroids, benzodiazepines or antipsychotics drugs. No patient received premedication. Before entering the operating room, venous access was established (18 G in the antecubital vein) where the first blood sample (Time 0) was collected to measure adrenocorticotropic hormone (ACTH), Cortisol, Growth hormone (GH) and prolactin (PRL) levels. Then a second venous access was established (18 G on the other arm) to start a fluid infusion (normal saline to replace half of the water deficit from preoperative fasting followed by a maintenance infusion of 2 ml/kg/h). Heart Rate (HR), Non Invasive Blood Pressure (NIBP), Bispectral Index (BIS), End-tidal CO2 (EtCO2) were recorded every 5 minutes. Patients were randomly assigned to receive two different dosages of remifentanil: 0,15 mcg/kg/min (group A) and 0,30 mcg/kg/min (group B) for the induction and the maintenance of anesthesia, using a computer generated randomization table (Table I). Anesthesia was induced with propofol 2 mg/kg, cisatracurium 0,15 mg/kg and remifentanil infusion of 0,15 mcg/Kg/min (Group A) or 0,3 mcg/Kg/min (Group B) was started. Anesthesia was maintained with desflurane at a variable concentration in order to maintain the BIS between 40 and 60. The second blood sample was collected at the trocar insertion (Time 1), and the third sample one hour after the end of the surgery (Time 2). Postoperative analgesia was standardized using intravenous acetaminophen 1 g and morphine 0,1 mg/kg 30 minutes before the end of the surgery. Rescue analgesia in Recovery Room was provided by intravenous tramadol 1 mg/Kg.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Rome, Italy, 00168
    • Catholic University Of Sacred Heart

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologist physical status I-II
• Undergoing laparoscopic cholecystectomy

Exclusion Criteria:

• patient refusal,
• thyroid disorders,
• diabetes mellitus,
• BMI > 30,
• use of corticosteroids, benzodiazepines or antipsychotics drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; remifentanil infusion of 0,15 mcg/Kg/min	Drug: Remifentanil Injectable Product; remifentanil: 0,15 mcg/kg/min
Active Comparator: Group B; remifentanil infusion of 0,3 mcg/Kg/min	Drug: Remifentanil Injectable Product; remifentanil: 0,15 mcg/kg/min

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
ACTH levels changes	changes between basal, incision,one hour after surgery
Cortisol levels changes	changes between basal, incision,one hour after surgery
Growth hormone levels changes	changes between basal, incision,one hour after surgery
prolactin levels changes	changes between basal, incision,one hour after surgery

Collaborators and Investigators

• Sponsor: Catholic University of the Sacred Heart
• Investigators: Principal Investigator: Flaminio Sessa, MD, Catholic University Rome

Publications and helpful links

General Publications

• Desborough JP. The stress response to trauma and surgery. Br J Anaesth. 2000 Jul;85(1):109-17. doi: 10.1093/bja/85.1.109. No abstract available.
• Jakeways MS, Mitchell V, Hashim IA, Chadwick SJ, Shenkin A, Green CJ, Carli F. Metabolic and inflammatory responses after open or laparoscopic cholecystectomy. Br J Surg. 1994 Jan;81(1):127-31. doi: 10.1002/bjs.1800810146.
• Marana E, Scambia G, Maussier ML, Parpaglioni R, Ferrandina G, Meo F, Sciarra M, Marana R. Neuroendocrine stress response in patients undergoing benign ovarian cyst surgery by laparoscopy, minilaparotomy, and laparotomy. J Am Assoc Gynecol Laparosc. 2003 May;10(2):159-65. doi: 10.1016/s1074-3804(05)60291-5.
• Adas G, Kemik A, Adas M, Koc B, Gurbuz E, Akcakaya A, Karahan S. Metabolic and inflammatory responses after ERCP. Int J Biomed Sci. 2013 Dec;9(4):237-42.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2008
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: December 14, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (Actual): December 20, 2017

Study Record Updates

• Last Update Posted (Actual): January 8, 2018
• Last Update Submitted That Met QC Criteria: January 5, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Remifentanil
• Other Study ID Numbers: CUSacredHeart

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No