Clinical trial NCT03534895: Does the Preoperative Midazolam Dose Affect Postoperative Pain?
Official title: Does the Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Randomized Controlled Trial in Ambulatory Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Pain, Postoperative
Keywords: midazolam
ambulatory surgery
Lead sponsor: Universidade do Porto
Sponsor class: OTHER
Collaborators: name: Centro Hospitalar de Entre o Douro e Vouga
name: Centro Hospitalar de Vila Nova de Gaia/Espinho
First posted: 2018-05-23
Enrollment: 168
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To investigate whether midazolam has any effect on postoperative pain in outpatient surgery, the investigators will assess the impact of different midazolam doses on pain scores 24h, 7 days and 3 months after ambulatory surgery.

The investigators hypothesize that patients being administered higher midazolam doses will refer more pain.

Detailed description: Systemic midazolam prescribed perioperatively might have impact on pain, with studies suggesting antinociceptive and hyperalgesic effects. Anxiety might be a confounder in this association. In order to investigate the effect of midazolam on postoperative pain, a clinical trial will be conducted in Portuguese ambulatory surgery units. A convenience sample with consecutive design will include patients admitted for open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery under spinal anesthesia. Patients will be randomized into 3 premedication groups, and this randomization will be stratified for each centre and each type of surgery. Postoperative pain will be blindly assessed by telephone interviews at 24h, 7 days, and 3 months.

The investigators will use multiple regression models to explore the interaction of midazolam dose with preoperative anxiety, gender and chronic benzodiazepine use, as they hypothesize there might be a differential effect of midazolam on postoperative pain amongst these subgroups.

Eligibility criteria: Inclusion Criteria:

* adult patients submitted to open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery in Portuguese ambulatory surgery units

Exclusion Criteria:

* psychiatric disorders
* alcoholism
* illiteracy or poor understanding of Portuguese language
* history of chronic pain under opioids
* recurrent surgery
* contraindication for midazolam or deep sedation
* contraindication for spinal anesthesia

Primary outcomes:
measure: Postoperative pain
timeFrame: Day 1 after surgery
Secondary outcomes:
measure: Postoperative pain
timeFrame: Day 7 after surgery
measure: Postoperative pain
timeFrame: Month 3 after surgery
measure: Pain interference in daily life
timeFrame: Day 1 after surgery
measure: Pain interference in daily life
timeFrame: Day 7 after surgery
measure: Pain interference in daily life
timeFrame: Month 3 after surgery
measure: Analgesic consumption
timeFrame: Day 1 after surgery
measure: Analgesic consumption
timeFrame: Day 7 after surgery
measure: Patient satisfaction
timeFrame: Day 7 after surgery
measure: Patient satisfaction
timeFrame: Month 3 after surgery
measure: Adverse events
timeFrame: Day 7 after surgery
measure: Global surgery recovery index
timeFrame: Month 3 after surgery
Other outcomes:
Locations:
city: Santa Maria Da Feira
country: Portugal
facility: Centro Hospitalar Entre Douro e Vouga, EPE
city: Vila Nova De Gaia
country: Portugal
facility: Centro Hospitalar Vila Nova de Gaia / Espinho, EPE
Study officials:
References:
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citation: Tatsuo MA, Salgado JV, Yokoro CM, Duarte ID, Francischi JN. Midazolam-induced hyperalgesia in rats: modulation via GABA(A) receptors at supraspinal level. Eur J Pharmacol. 1999 Apr 1;370(1):9-15. doi: 10.1016/s0014-2999(99)00096-5.
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citation: Day MA, Rich MA, Thorn BE, Berbaum ML, Mangieri EA. A placebo-controlled trial of midazolam as an adjunct to morphine patient-controlled analgesia after spinal surgery. J Clin Anesth. 2014 Jun;26(4):300-8. doi: 10.1016/j.jclinane.2013.12.011. Epub 2014 Jun 2.
citation: Okulicz-Kozaryn I, Kaminska E, Luczak J, Szczawinska K, Kotlinska-Lemieszek A, Baczyk E, Mikolajczak P. The effects of midazolam and morphine on analgesic and sedative activity of ketamine in rats. J Basic Clin Physiol Pharmacol. 2000;11(2):109-25. doi: 10.1515/jbcpp.2000.11.2.109.
citation: Hasani A, Maloku H, Sallahu F, Gashi V, Ozgen SU. Preemptive analgesia with midazolam and diclofenac for hernia repair pain. Hernia. 2011 Jun;15(3):267-72. doi: 10.1007/s10029-010-0772-y. Epub 2010 Dec 28.