Pregabalin Effects on Hypotensive Anesthesia During Spine Surgery.

Elective lumbar spine surgical procedures are commonly performed under controlled hypotension during general anesthesia. That is beneficial to limit the intraoperative blood loss and transfusions and improves surgical field. Deliberate hypotension could be achieved via various medications but mostly associated with significant side effects. Pregabalin effectively augmented hypotensive anesthesia. The hypothesis is that Pregabalin 150 mg single preoperative dose may augment intraoperative deliberate hypotension that will be reflected on blood loss and nitroglycerin consumption.

Study Overview

• Status: Completed
• Conditions: Spine Surgery
• Intervention / Treatment: Drug: Pregabalin; Drug: placebo

Detailed Description

An arterial line will be established then general anesthesia will be conducted. After adequate preoxygenation, anesthesia induction by IV fentanyl 1.5µg/kg, propofol 2 mg/kg, and atracurium 0.5 mg/kg then appropriated size tracheal tube. The ventilator settings will be adjusted to maintain the end-tidal carbon dioxide tension (ETco2) at 30-35 mm Hg. Anesthesia will be maintained by isoflurane concentration 1.2%, with 40% oxygen in air then IV infusion of fentanyl 0.05 mcg/kg/min was started while atracurium 0.1 mg/kg incremental dose as required. Then patients will be turned into the prone position above pad support permitting free hanging of the abdomen. Intraoperatively, the target mean arterial arterial blood pressure (MBP) is 55-65 mm Hg. After surgical incision, if MBP exceeds 65 mm Hg (defined as hypertension) it will be managed by: increasing isoflurane MAC up to 2%, if no response after 5 min, Nitroglycerin infusion initiated at 0.5 mcg/kg/min to 40 mcg/kg/min. Hypotension (MBP <55 mm Hg) will be treated by stopping nitroglycerin, proper compensation of losses, reducing Isoflurane MAC. If persisted; vasoactive drugs will be used. Bradycardia (HR <50 beat/min.), treated with 0.01 mg/kg atropine IV increments.

The nitroglycerin infusion will be stopped after the finial surgical hemostasis. Fentanyl infusion will be stopped before ligament sutures. Isoflurane will be closed after the last surgical suture. After dressing, patient will be turned to the supine position and morphine 0.025 mg/kg IV will be administered then 0.04 mg/kg neostigmine and 0.015 mg/kg atropine for reversal. Extubation will be done after establishment of acceptable spontaneous respiration.

• Study Type: Interventional
• Enrollment (Actual): 106
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Egypt
  • Dakahlia
    • Mansourah, Dakahlia, Egypt, 35516
      • Mansoura University Hospital
    • Mansourah,, Dakahlia, Egypt, 35516
      • Delta Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• American Society of Anesthesiologists (ASA) score I-II
• admitted to undergo lumbar discectomy or spinal fixation surgery under general anesthesia

Exclusion Criteria:

• Patients on anti-hypertensive treatment, diuretics, corticosteroids, pregabalin, gabapentin, anticonvulsants, antipsychotics,
• alcohol addiction or drug abuse
• patients with history of allergy to any drug used in the study .
• pregnant or nursing women
• patients with peripheral neuropathy, endocrinal diseases, bleeding abnormality,
• cardiac, hepatic or renal impairment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Pregabalin group; (n=53):	Drug: Pregabalin; Pregabalin 150 mg capsule, one h preinduction of general anesthesia; Other Names: (LYRICA® 150 mg capsule- PFIZER)
PLACEBO_COMPARATOR: placebo group; (n=53):	Drug: placebo; given a placebo identical capsule once one hour before anesthesia; Other Names: control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nitroglycerin consumption	the total nitroglycerin consumption in milligram to maintain the target mean arterial pressure (MAP) 55- 65 mmHg.	Intraoperative

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Estimated blood loss	towels are weighted, plus suction volume without irrigation fluids in milliter.	intraoperative
The number of transfused blood unites	Packed red blood cell unites	intraoperative
heart rate (HR)	in beat/min	Basal, during intubation, then at 1, 5, 30, 60, 90, 120, 150, 180, 210 minutes post extubation, then postoperatively at 1 and 2 hours.
end-tidal isoflurane concentration	in percent	at 30, 60, 90, 120, 150 , 180, 210 minutes after intubation.
Surgeon satisfaction about the field	using a six-point scale (0 = no bleeding, virtually bloodless field; 5 = uncontrolled) bleeding).	within 2 hours from the end of surgery.
Sedation	(Ramsay sedation scale)	at 0, 2, 4, 6, 12, 24 hours postoperatively
The time to the first request of analgesia.	in hours	24 hours postoperative
Postoperative pain	(VAS 0-10 scale) 10 is the worst pain	at 0, 2, 4, 6, 12, 24 hours postoperatively.
The total morphine consumption	in mg	in the 1st 24 hours postoperatively
Frequency of adverse effects	dizziness, headache, nausea and vomiting, or pruritus.	during the first 24 hours postoperatively
Peak airway pressures	in centimeter water	10 minutes after settled prone position
invasive mean arterial blood pressure (MAP)	in millimeter mercury (mmHg)	Basal, during intubation, then at 1, 5, 30, 60, 90, 120, 150, 180, 210 minutes post extubation, then postoperatively at 1 and 2 hours.

Collaborators and Investigators

• Sponsor: Mansoura University
• Investigators: Principal Investigator: Alaa Mazy, Faculty of Medicine, Mansoura University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 8, 2018
• Primary Completion (ACTUAL): March 30, 2018
• Study Completion (ACTUAL): April 30, 2019

Study Registration Dates

• First Submitted: September 26, 2017
• First Submitted That Met QC Criteria: September 28, 2017
• First Posted (ACTUAL): October 4, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 18, 2020
• Last Update Submitted That Met QC Criteria: September 16, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: Pregabalin, hypotensive anesthesia, blood loss, analgesia
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Anti-Anxiety Agents; Anticonvulsants; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Pregabalin
• Other Study ID Numbers: R/17.07.107

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: all data will be available after about 6 months
• IPD Sharing Time Frame: Immediately following publication. No end date.
• IPD Sharing Access Criteria: e mail: alaa_mazy@yahoo.com
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

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