Does the Preoperative Midazolam Dose Affect Postoperative Pain?

Pain, Postoperative Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03534895
• Other study ID #: Midazolam RCT
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: May 2019
• Est. completion date: August 2020

Study information

• Verified date: May 2018
• Source: Universidade do Porto
• Contact: Caroline Dahlem, MD
• Phone: +351968061851
• Email: caroline.dahlem[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 168
• Est. completion date: August 2020
• Est. primary completion date: May 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pain, Postoperative

Intervention

Drug:
• Midazolam Injectable Solution
intravenous

Other:
• Normal saline
intravenous

Procedure:
• Spinal anesthesia
8mg of heavy bupivacaine 0.5% injected in the subarachnoid space, during lateral decubitus
• Surgery
Open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery

Drug:
• Postoperative analgesia
IV acetaminophen 1g + IV ketorolac 30mg
• Rescue analgesia
Tramadol 2mg/Kg IV in 100mL of normal saline, if pain NRS>3.
• Wound infiltration
Wound infiltration with 10mL of ropivacaine 0.75%, in open inguinal hernia repair
• Analgesia at home
Oral acetaminophen 1g 6/6h + ibuprofen 400mg 8/8h (+ rescue analgesia with tramadol 50mg 6/6h)

Locations

Country	Name	City	State
Portugal	Centro Hospitalar Entre Douro e Vouga, EPE	Santa Maria Da Feira
Portugal	Centro Hospitalar Vila Nova de Gaia / Espinho, EPE	Vila Nova De Gaia

Sponsors (3)

Lead Sponsor	Collaborator
Universidade do Porto	Centro Hospitalar de Entre o Douro e Vouga, Centro Hospitalar de Vila Nova de Gaia/Espinho

Country where clinical trial is conducted

Portugal, 

References & Publications (7)

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. — View Citation

Frölich MA, Zhang K, Ness TJ. Effect of sedation on pain perception. Anesthesiology. 2013 Mar;118(3):611-21. doi: 10.1097/ALN.0b013e318281592d. — View 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. — View Citation

Kain ZN, Sevarino F, Pincus S, Alexander GM, Wang SM, Ayoub C, Kosarussavadi B. Attenuation of the preoperative stress response with midazolam: effects on postoperative outcomes. Anesthesiology. 2000 Jul;93(1):141-7. — View Citation

Mantegazza P, Parenti M, Tammiso R, Vita P, Zambotti F, Zonta N. Modification of the antinociceptive effect of morphine by centrally administered diazepam and midazolam. Br J Pharmacol. 1982 Apr;75(4):569-72. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Analgesic consumption	Total analgesic drugs taken in a time period (first day after surgery)	Day 1 after surgery
Secondary	Analgesic consumption	Total analgesic drugs taken in a time period (first week after surgery)	Day 7 after surgery
Secondary	Patient satisfaction	NRS 0-10	Day 7 after surgery
Secondary	Patient satisfaction	NRS 0-10	Month 3 after surgery
Secondary	Adverse events	Number of patients with adverse events like bleeding, nausea, uncontrolled pain	Day 7 after surgery
Secondary	Global surgery recovery index	Global surgery recovery index (0-100%)	Month 3 after surgery