Clinical trial NCT04708353: Oral Pregabalin Premedication for Postoperative Pain Relief
Official title: Effect of Two Different Doses of Oral Pregabalin Premedication for Postoperative Pain Relief After Gynecological Surgeries
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Gynecologic Disease
Keywords: Oral Pregabalin
Postoperative Pain Relief
Gynecological Surgeries
Lead sponsor: Zagazig University
Sponsor class: OTHER_GOV
First posted: 2021-01-13
Enrollment: 90
Sex: FEMALE
Minimum age (years): 21
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The patients will be allocated randomly using computer generated randomization table into three equal groups
Primary purpose: TREATMENT

Brief summary: Pain management after gynecological surgeries is essential for early mobilization of the patient, decrease postoperative complication and hospital stay. The use of opioids is associated with adverse effects such as nausea, vomiting, ileus, pruritus, sedation and respiratory depression.

Previous studies stated that pregabalin has been used to reduce pre-operative anxiety, acute postoperative pain, postoperative opioid requirements, postoperative nausea, vomiting and postoperative delirium. The most effective dose of pregabalin to relief postoperative pain with least side effect is still under trial.

In this study we will compare between two different doses of pregabalin when given as oral premedication in patients undergoing gynecological surgeries under spinal anesthesia regarding postoperative pain in order to reduce opioids consumption and subsequently avoid opioid-related adverse effects.

Detailed description: Postoperative pain, nausea and vomiting continue to be one of the most common and unpleasant complications after surgery. The traditional pain treatment with opioids alone is not adequate any more. To optimize pain treatment and postoperative outcome, new analgesics and new combination of already existing analgesics are searched for.

Pain after gynecological surgery usually severe. Uncontrolled acute post-operative pain is associated with dissatisfaction, post-operative complications and considered as a strong risk factor for development of chronic pain. An enhanced recovery pathway for gynecological surgery must include a strategy to effectively control post-operative pain and allow attainment of other Enhanced Recovery After Surgery (ERAS) targets such as early mobilization and return to oral diet whilst reducing the need for opiates.

Beyond increasing the risk of developing opioid use disorder, perioperative opioid consumption may produce undesirable side effects such as nausea, vomiting, constipation, ileus, pruritus, altered mental status, urinary retention, respiratory complications and increased length of hospital stay. While many of these side effects are frustrating to patient in the immediate postoperative period, the most dangerous effects are those that affect the respiratory system such as opioid-induced respiratory depression (ORD) which consider as a significant cause of brain damage and death in the postoperative period.

Opioid reduction strategies prove useful for decreasing total opioid dose and, in turn, their associated adverse effects. Such strategies may include adjuvant non opioid analgesics such as α-2 agonists, gabapentinoids and N-methyl-D-aspartate receptor agonists as well as local, regional or neuraxial anesthesia and modification of surgical technique where possible for operative patients.

Pregabalin is a new synthetic molecule and a structural derivative of the inhibitory neurotransmitter gamma-amino butyric acid. It is a α2-δ ligand that has analgesic, anticonvulsant, anxiolytic and sleep-modulating activities. Pregabalin binds potently to the α2-δ subunit of calcium channels, resulting in a reduction in the release of several neurotransmitters including glutamate, noradrenaline, serotonin, dopamine and substance P.

Pregabalin could reduce the hyperexcitability of dorsal horn neurons induced by tissue damage; therefore it may be useful in the postsurgical pain prevention.

In 2015, a meta-analysis published in British Medical Journal (BMJ) suggested that pregabalin could improve postoperative analgesia and opioid-related adverse effects namely, vomiting and visual disturbances after surgery. However, the use of the pregabalin for acute postoperative pain is still under trial though widely reported.

Eligibility criteria: Inclusion Criteria:

* Physical status: ASA I-II
* BMI ≥ 20kg/m2 \& ≤ 35kg/m2,
* Written informed consent from the patient.

Exclusion Criteria:

* Patients with known history of allergy to study drugs,
* Patients on ACE inhibitors, anticonvulsant therapy or any drug interacting with pregabalin,
* Patients on chronic alcohol, opioid, tranquilizer or sedative use,
* Patient with renal impairment or heart failure,
* Pregnant females, Psychological, mental disorders or depression,
* Patients receiving anticoagulants therapy or suspected coagulopathy,
* Patients already on pregbalin or gabapentin therapy.

Primary outcomes:
measure: changes in Postoperative pain
timeFrame: at 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours postoperatively
Secondary outcomes:
measure: The level of sedation
timeFrame: at 2, 4, 6, 8, 10, 12, 16, 20 and 24 hours postoperatively
measure: Total amount of rescue analgesic
timeFrame: in the first 24 hours
Other outcomes:
Locations:
city: Zagazig
country: Egypt
facility: faculty of medicine, Zagazig university
state: Elsharqya
Study officials:
References:
citation: Guay DR. Pregabalin in neuropathic pain: a more "pharmaceutically elegant" gabapentin? Am J Geriatr Pharmacother. 2005 Dec;3(4):274-87.
citation: Dahl JB, Mathiesen O, Moiniche S. 'Protective premedication': an option with gabapentin and related drugs? A review of gabapentin and pregabalin in in the treatment of post-operative pain. Acta Anaesthesiol Scand. 2004 Oct;48(9):1130-6. doi: 10.1111/j.1399-6576.2004.00484.x.
citation: Mishriky BM, Waldron NH, Habib AS. Impact of pregabalin on acute and persistent postoperative pain: a systematic review and meta-analysis. Br J Anaesth. 2015 Jan;114(1):10-31. doi: 10.1093/bja/aeu293. Epub 2014 Sep 10.
citation: Balaban F, Yagar S, Ozgok A, Koc M, Gullapoglu H. A randomized, placebo-controlled study of pregabalin for postoperative pain intensity after laparoscopic cholecystectomy. J Clin Anesth. 2012 May;24(3):175-8. doi: 10.1016/j.jclinane.2011.06.027. Epub 2012 Mar 28.