Does Midazolam Affect Postoperative Pain?

Does Preoperative Midazolam Dose Affect Postoperative Pain? - a Multicentric Observational Study in Open Inguinal Hernia Repair

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 open inguinal hernia repair.

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

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Midazolam injection

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 prospective cohort study will be conducted in four Portuguese ambulatory surgery units. A convenience sample with consecutive design will include patients admitted for open inguinal hernia repair. After anxiety and pain evaluation, a tailored dose of midazolam will be administered as premedication according to the anesthetist's best judgement within each unit's protocol (routine care; this dose may be null). Subsequent anesthesia and analgesia will be standardized. Postoperative pain will be blindly assessed by telephone interviews at 24h, 7 days, and 3 months. Statistical analysis will be performed separately for each gender, centre and type of anesthesia, adjusting for preoperative anxiety and other confounding variables with multivariate analysis.

The investigators intend to clarify the relation between anxiety, preoperative midazolam and postoperative pain.

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• Portugal
  • Aveiro, Portugal
    • Centro Hospitalar Baixo Vouga, EPE
  • Faro, Portugal
    • Centro Hospitalar Universitario do Algarve
  • Santa Maria Da Feira, Portugal
    • Centro Hospitalar Entre Douro e Vouga, EPE
  • Vila Nova De Gaia, Portugal
    • Centro Hospitalar Vila Nova de Gaia / Espinho, EPE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Consecutive adult patients proposed for open inguinal hernia repair in Portuguese ambulatory surgery units, under general or spinal anesthesia.

Description

Inclusion Criteria:

- adults proposed for open inguinal hernia repair in Portuguese ambulatory surgery units

Exclusion Criteria:

• psychiatric disorders
• alcoholism
• illiteracy or poor understanding of the Portuguese language
• history of chronic pain under opioids
• recurrent surgery

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain	Pain numeric rating scale (NRS) 0-10	24h after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative pain	Pain NRS	7 days after surgery
Postoperative pain	Pain NRS	3 months after surgery
Patient satisfaction	NRS	7 days after surgery
Patient satisfaction	NRS	3 months after surgery
Analgesic consumption	Total analgesic drugs taken in a time period	24h after surgery
Analgesic consumption	Total analgesic drugs taken in a time period	7 days after surgery
Adverse events	Number of patients with adverse events like bleeding, nausea, uncontrolled pain	7 days after surgery
Global surgery recovery index	Global surgery recovery index	3 months after surgery

Collaborators and Investigators

• Sponsor: Universidade do Porto
• Investigators: Principal Investigator: Caroline Dahlem, MD, UPorto /CINTESIS

Publications and helpful links

General Publications

• 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. doi: 10.1111/j.1476-5381.1982.tb09175.x.
• 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.
• 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.
• Frolich MA, Zhang K, Ness TJ. Effect of sedation on pain perception. Anesthesiology. 2013 Mar;118(3):611-21. doi: 10.1097/ALN.0b013e318281592d.
• 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. doi: 10.1097/00000542-200007000-00024.
• Coulthard P, Rood JP. An investigation of the effect of midazolam on the pain experience. Br J Oral Maxillofac Surg. 1992 Aug;30(4):248-51. doi: 10.1016/0266-4356(92)90268-n.
• 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.
• 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.
• Ong CK, Seymour RA, Tan JM. Sedation with midazolam leads to reduced pain after dental surgery. Anesth Analg. 2004 May;98(5):1289-93, table of contents. doi: 10.1213/01.ane.0000111107.18755.cc.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 12, 2018
• Primary Completion (ACTUAL): June 5, 2020
• Study Completion (ACTUAL): March 5, 2021

Study Registration Dates

• First Submitted: April 9, 2018
• First Submitted That Met QC Criteria: April 15, 2018
• First Posted (ACTUAL): April 17, 2018

Study Record Updates

• Last Update Posted (ACTUAL): May 18, 2021
• Last Update Submitted That Met QC Criteria: May 15, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Inguinal hernia; Midazolam
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Midazolam
• Other Study ID Numbers: Midazolam OBS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in this article might be shared with other researchers after deidentification.
• IPD Sharing Time Frame: Beginning 6 months following article publication.
• IPD Sharing Access Criteria: Proposals should be directed to caroline.dahlem@gmail.com. To gain access, data requestors will need to sign a data access agreement.
• 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
• product manufactured in and exported from the U.S.: No