Effect of Dexmedetomidine on Plasmatic Cortisol Response in Transsphenoidal Surgery

Effect of Dexmedetomidine as Anesthetic Coadjuvant on Plasmatic Cortisol Response in Transsphenoidal Surgery for Pituitary Tumors

Use of dexmedetomidine in pituitary tumor resection surgery as adjuvant drug and its relation to cortisol levels during postoperative period.

Study Overview

• Status: Unknown
• Conditions: Pituitary Neoplasms
• Intervention / Treatment: Drug: Dexmedetomidine; Drug: Sodium Chloride 0.9%

Detailed Description

Transsphenoidal resection of pituitary tumors is the neurosurgical procedure of choice to remove most of the tumors of the sellar region. Sometimes the intervention produces dysfunction of the hypothalamic-pituitary axis, and although most are transient, the risk associated with post-operative hypocortisolism determines its evaluation early in the postoperative period and the possibility of steroidal supplementation posteriorly. It is described that dexmedetomidine can be used as an adjuvant drug in this type of surgery being useful in reduction of total consumption of opioids and anesthetic gases, maintain hemodynamic stability and less time to recovery from anesthesia. Due to its sympatholytic effect, dexmedetomidine has been found to alter the intraoperative common neuroendocrine response generating lower levels of cortisol in the postoperative period than patients in which is not used.

The main objective of this study is to evaluate corticosteroid axis response (cortisol and adrenocorticotropic hormone) in patients undergoing transsphenoidal surgery under anesthesia with dexmedetomidine. A single-center randomized double-blind clinical trial will be conducted that will compare two groups of patients, one of which will be given dexmedetomidine (Dex group) and another group who will receive a placebo (control group). In addition the incidence of perioperative complications (nausea, vomiting, diabetes insipidus), intraoperative hemodynamics and patient comfort. The investigators expect that the normal stress response to surgery measured by cortisol and adrenocorticotropic hormone in the postoperative period will be reduced in the dexmedetomidine arm. This effect should be transient and attributed to use of dexmedetomidine and not to surgery.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 4

Contacts and Locations

Study Locations

• Chile
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 8330024
      • Recruiting
      • Division de Anestesia - Pontificia Universidad Catolica de Chile
      • Contact: Fernando R Altermatt, MSc; Phone Number: 56-2-23543270; Email: fernando.altermatt@gmail.com
      • Contact: Hernan E Auad, MD; Phone Number: 56-2-23543270; Email: hernan_auad@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists physical status I or II.
• Pituitary tumour: non-functional macroadenoma, Rathke's cleft cyst, acromegaly.
• Normal hypothalamic-pituitary-adrenal axis by hormone levels measurement previous to surgery.

Exclusion Criteria:

• Cushing disease.
• Pituitary apoplexy.
• Craniopharyngioma.
• Chronic corticosteroid use.
• Hemodynamic instability.
• Altered consciousness (Glasgow Coma Scale score less than 15).
• Atrioventricular block in any degree.
• Preoperative bradycardia.
• Alpha 2 agonist use (clonidine, alpha-methyldopa)
• Pregnancy or breast feeding.
• Known allergy to any of the study drugs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexmedetomidine; Use of dexmedetomidine during surgery (1 mcg/kg in 10 minutes, then infusion at 0.7 mcg/kg/h)	Drug: Dexmedetomidine; At start of anesthesia, bolus of 1 mcg/kg of dexmedetomidine over 10 minutes and then infusion of 0.7 mcg/kg/h during surgery will be administered.; Other Names: Precedex
Placebo Comparator: Placebo; Use of crystalloid solution (sodium chloride 0.9%), injection pump programmed with drug "Dexmedetomidine" with 1 mcg/kg in 10 minutes, infusion 0.7 mcg/kg/h.	Drug: Sodium Chloride 0.9%; Sodium chloride 0.9% with a pump programmed in same way as Dexmedetomidine pump; Other Names: Saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortisol plasmatic levels	Venous blood sample	24 hours after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adrenocorticotropin hormone	Venous blood sample	One hour after surgery, 24 hours after surgery, 48 hours after surgery
Hemodynamics	Heart rate and arterial pressure	From start of anesthesia to end of anesthesia
Nausea and vomiting	Semiquantitative measure	24 hours after surgery
Pain	By visual analogue scale	24 hours after surgery
Patient comfort	Scale ranging from 1 (very unsatisfied) to 5 (very satisfied)	24 hours after discharge from hospital
Diabetes insipidus incidence	Clinical diagnosis by urine output (polyuria over 3 liters or urine per day) and/or hypernatremia (plasmatic sodium over 145 meq/L)	24 hours after surgery and 3 months after surgery
Cerebrospinal fluid fistula	Clinical diagnosis made by neurosurgeon	3 months after surgery
Cortisol plasmatic levels	Venous blood sample	1 hour after surgery, 48 hours after surgery, 3 months after surgery

Collaborators and Investigators

• Sponsor: Pontificia Universidad Catolica de Chile
• Investigators: Principal Investigator: Juan C Pedemonte, MD, Physician; Principal Investigator: Pablo Villanueva, MD, Assisstant adjunct professor

Publications and helpful links

General Publications

• Bekker A, Haile M, Kline R, Didehvar S, Babu R, Martiniuk F, Urban M. The effect of intraoperative infusion of dexmedetomidine on the quality of recovery after major spinal surgery. J Neurosurg Anesthesiol. 2013 Jan;25(1):16-24. doi: 10.1097/ANA.0b013e31826318af.
• Bhana N, Goa KL, McClellan KJ. Dexmedetomidine. Drugs. 2000 Feb;59(2):263-8; discussion 269-70. doi: 10.2165/00003495-200059020-00012.
• Mukhtar AM, Obayah EM, Hassona AM. The use of dexmedetomidine in pediatric cardiac surgery. Anesth Analg. 2006 Jul;103(1):52-6, table of contents. doi: 10.1213/01.ane.0000217204.92904.76.
• Hout WM, Arafah BM, Salazar R, Selman W. Evaluation of the hypothalamic-pituitary-adrenal axis immediately after pituitary adenomectomy: is perioperative steroid therapy necessary? J Clin Endocrinol Metab. 1988 Jun;66(6):1208-12. doi: 10.1210/jcem-66-6-1208.
• Carrasco CA, Villanueva G P. [Selective use of glucocorticoids during the perioperative period of transsphenoidal surgery for pituitary tumors]. Rev Med Chil. 2014 Sep;142(9):1113-9. doi: 10.4067/S0034-98872014000900004. Spanish.
• Ali Z, Prabhakar H, Bithal PK, Dash HH. Bispectral index-guided administration of anesthesia for transsphenoidal resection of pituitary tumors: a comparison of 3 anesthetic techniques. J Neurosurg Anesthesiol. 2009 Jan;21(1):10-5. doi: 10.1097/ANA.0b013e3181855732.
• Gopalakrishna KN, Dash PK, Chatterjee N, Easwer HV, Ganesamoorthi A. Dexmedetomidine as an Anesthetic Adjuvant in Patients Undergoing Transsphenoidal Resection of Pituitary Tumor. J Neurosurg Anesthesiol. 2015 Jul;27(3):209-15. doi: 10.1097/ANA.0000000000000144.
• Raekallio MR, Kuusela EK, Lehtinen ME, Tykkylainen MK, Huttunen P, Westerholm FC. Effects of exercise-induced stress and dexamethasone on plasma hormone and glucose concentrations and sedation in dogs treated with dexmedetomidine. Am J Vet Res. 2005 Feb;66(2):260-5. doi: 10.2460/ajvr.2005.66.260.
• Nomikos P, Ladar C, Fahlbusch R, Buchfelder M. Impact of primary surgery on pituitary function in patients with non-functioning pituitary adenomas -- a study on 721 patients. Acta Neurochir (Wien). 2004 Jan;146(1):27-35. doi: 10.1007/s00701-003-0174-3. Epub 2004 Jan 7. Erratum In: Acta Neurochir (Wien). 2004 Apr;146(6):433.

Study record dates

Study Major Dates

• Study Start: September 1, 2015
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): August 1, 2017

Study Registration Dates

• First Submitted: September 6, 2015
• First Submitted That Met QC Criteria: September 11, 2015
• First Posted (Estimate): September 15, 2015

Study Record Updates

• Last Update Posted (Estimate): October 12, 2016
• Last Update Submitted That Met QC Criteria: October 10, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Cortisol; Dexmedetomidine; Pituitary; Transsphenoidal
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Endocrine Gland Neoplasms; Hypothalamic Diseases; Hypothalamic Neoplasms; Supratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Pituitary Neoplasms; Pituitary Diseases; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-Agonists; Adrenergic Agonists; Hypnotics and Sedatives; Dexmedetomidine
• Other Study ID Numbers: 15-095

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED