Does the Preoperative Midazolam Dose Affect Postoperative Pain?

Study Overview
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Brief Summary
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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
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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.

Official Title
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Does the Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Randomized Controlled Trial in Ambulatory Surgery

Conditions
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Pain, Postoperative

Intervention / Treatment
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* Drug: Midazolam Injectable Solution
* Other: Normal saline
* Procedure: Spinal anesthesia
* Procedure: Surgery
* Drug: Postoperative analgesia
* Drug: Rescue analgesia
* Drug: Wound infiltration
* Drug: Analgesia at home


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PC1<br>5mL normal saline intravenous, single-administration, as pre-medication | Other: Normal saline<br>* intravenous<br>Procedure: Spinal anesthesia<br>* 8mg of heavy bupivacaine 0.5% injected in the subarachnoid space, during lateral decubitus<br>Procedure: Surgery<br>* Open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery<br>Drug: Postoperative analgesia<br>* IV acetaminophen 1g + IV ketorolac 30mg<br>Drug: Rescue analgesia<br>* Tramadol 2mg/Kg IV in 100mL of normal saline, if pain NRS>3.<br>Drug: Wound infiltration<br>* Wound infiltration with 10mL of ropivacaine 0.75%, in open inguinal hernia repair<br>Drug: Analgesia at home<br>* Oral acetaminophen 1g 6/6h + ibuprofen 400mg 8/8h (+ rescue analgesia with tramadol 50mg 6/6h)<br>|
| Experimental: PC2<br>midazolam 0.02mg/Kg in 5mL normal saline, intravenous, single-administration, as pre-medication | Drug: Midazolam Injectable Solution<br>* intravenous<br>* Other names: Dormicum;Other: Normal saline<br>* intravenous<br>Procedure: Spinal anesthesia<br>* 8mg of heavy bupivacaine 0.5% injected in the subarachnoid space, during lateral decubitus<br>Procedure: Surgery<br>* Open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery<br>Drug: Postoperative analgesia<br>* IV acetaminophen 1g + IV ketorolac 30mg<br>Drug: Rescue analgesia<br>* Tramadol 2mg/Kg IV in 100mL of normal saline, if pain NRS>3.<br>Drug: Wound infiltration<br>* Wound infiltration with 10mL of ropivacaine 0.75%, in open inguinal hernia repair<br>Drug: Analgesia at home<br>* Oral acetaminophen 1g 6/6h + ibuprofen 400mg 8/8h (+ rescue analgesia with tramadol 50mg 6/6h)<br>|
| Experimental: PC3<br>midazolam 0.06mg/Kg in 5mL normal saline, intravenous, single-administration, as pre-medication | Drug: Midazolam Injectable Solution<br>* intravenous<br>* Other names: Dormicum;Other: Normal saline<br>* intravenous<br>Procedure: Spinal anesthesia<br>* 8mg of heavy bupivacaine 0.5% injected in the subarachnoid space, during lateral decubitus<br>Procedure: Surgery<br>* Open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery<br>Drug: Postoperative analgesia<br>* IV acetaminophen 1g + IV ketorolac 30mg<br>Drug: Rescue analgesia<br>* Tramadol 2mg/Kg IV in 100mL of normal saline, if pain NRS>3.<br>Drug: Wound infiltration<br>* Wound infiltration with 10mL of ropivacaine 0.75%, in open inguinal hernia repair<br>Drug: Analgesia at home<br>* Oral acetaminophen 1g 6/6h + ibuprofen 400mg 8/8h (+ rescue analgesia with tramadol 50mg 6/6h)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | Assessed by the Brief Pain Inventory severity score (24h recall time): mean of 4 items assessing pain at the moment of the interview, on average, at its least and at its worst during the last 24h | Day 1 after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | Assessed by the Brief Pain Inventory severity score (24h recall time): mean of 4 items assessing pain at the moment of the interview, on average, at its least and at its worst during the last 24h. Features of neuropathic pain as assessed by DN4 patient-reported symptoms | Day 7 after surgery | 
| Postoperative pain | Assessed by the Brief Pain Inventory severity score (24h recall time): mean of 4 items assessing pain at the moment of the interview, on average, at its least and at its worst during the last 24h. Features of neuropathic pain as assessed by DN4 patient-reported symptoms | Month 3 after surgery | 
| Pain interference in daily life | Assessed by the Brief Pain Inventory interference score (24h recall time): interference of pain in general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. | Day 1 after surgery | 
| Pain interference in daily life | Assessed by the Brief Pain Inventory interference score (24h recall time): interference of pain in general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. | Day 7 after surgery | 
| Pain interference in daily life | Assessed by the Brief Pain Inventory interference score (24h recall time): interference of pain in general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. | Month 3 after surgery | 
| Analgesic consumption | Total analgesic drugs taken in a time period (first day after surgery) | Day 1 after surgery | 
| Analgesic consumption | Total analgesic drugs taken in a time period (first week after surgery) | Day 7 after surgery | 
| Patient satisfaction | NRS 0-10 | Day 7 after surgery | 
| Patient satisfaction | NRS 0-10 | Month 3 after surgery | 
| Adverse events | Number of patients with adverse events like bleeding, nausea, uncontrolled pain | Day 7 after surgery | 
| Global surgery recovery index | Global surgery recovery index (0-100%) | Month 3 after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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midazolam, ambulatory surgery