Does the Preoperative Midazolam Dose Affect Postoperative Pain?

NCT03534895 | Unknown Phase 4

• 1 other identifier: Midazolam RCT
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 2

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.

Conditions

Pain, Postoperative

Keywords

midazolam; ambulatory surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (11)

• Postoperative pain

  Day 7 after surgery

• Postoperative pain

  Month 3 after surgery

• Pain interference in daily life

  Day 1 after surgery

• Pain interference in daily life

  Day 7 after surgery

• Pain interference in daily life

  Month 3 after surgery

Study Arms (3)

PC1

PLACEBO COMPARATOR

5mL normal saline intravenous, single-administration, as pre-medication

Other: Normal saline; Procedure: Spinal anesthesia; Procedure: Surgery; Drug: Postoperative analgesia; Drug: Rescue analgesia; Drug: Wound infiltration; Drug: Analgesia at home

PC2

EXPERIMENTAL

midazolam 0.02mg/Kg in 5mL normal saline, intravenous, single-administration, as pre-medication

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

PC3

EXPERIMENTAL

midazolam 0.06mg/Kg in 5mL normal saline, intravenous, single-administration, as pre-medication

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

Interventions

Midazolam Injectable Solution DRUG

intravenous

Also known as: Dormicum

PC2; PC3

Normal saline OTHER

intravenous

PC1; PC2; PC3

Spinal anesthesia PROCEDURE

8mg of heavy bupivacaine 0.5% injected in the subarachnoid space, during lateral decubitus

PC1; PC2; PC3

Surgery PROCEDURE

Open inguinal hernia repair, varicose vein stripping, knee arthroscopy or hallux valgus surgery

PC1; PC2; PC3

Postoperative analgesia DRUG

IV acetaminophen 1g + IV ketorolac 30mg

PC1; PC2; PC3

Rescue analgesia DRUG

Tramadol 2mg/Kg IV in 100mL of normal saline, if pain NRS\>3.

PC1; PC2; PC3

Wound infiltration DRUG

Wound infiltration with 10mL of ropivacaine 0.75%, in open inguinal hernia repair

PC1; PC2; PC3

Analgesia at home DRUG

Oral acetaminophen 1g 6/6h + ibuprofen 400mg 8/8h (+ rescue analgesia with tramadol 50mg 6/6h)

PC1; PC2; PC3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Universidade do Porto: lead
• Centro Hospitalar de Entre o Douro e Vouga: collaborator
• Centro Hospitalar de Vila Nova de Gaia/Espinho: collaborator

Study Sites (2)

Centro Hospitalar Entre Douro e Vouga, EPE

Santa Maria da Feira, Portugal

Location

Centro Hospitalar Vila Nova de Gaia / Espinho, EPE

Vila Nova de Gaia, Portugal

Location

Related Publications (7)

• 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.

  PMID: 6121598 BACKGROUND

• 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.

  PMID: 10323274 BACKGROUND

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

  PMID: 23314164 BACKGROUND

• 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.

  PMID: 10861157 BACKGROUND

• 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.

  PMID: 24882605 BACKGROUND

• 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.

  PMID: 11037766 BACKGROUND

• 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.

  PMID: 21188440 BACKGROUND

MeSH Terms

Conditions

Pain, Postoperative

Interventions

Midazolam; Saline Solution; Anesthesia, Spinal; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Pain; Neurologic Manifestations; Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations; Anesthesia, Conduction; Anesthesia; Anesthesia and Analgesia

Central Study Contacts

Caroline Dahlem, MD

CONTACT

+351968061851; caroline.dahlem@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 22, 2018
• First Posted: May 23, 2018
• Study Start: May 1, 2019
• Primary Completion: May 1, 2020
• Study Completion: August 1, 2020
• Last Updated: May 23, 2018

Record last verified: 2018-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 6 months following article publication.
• Access Criteria: Proposals should be directed to caroline.dahlem@gmail.com. To gain access, data requestors will need to sign a data access agreement.

Locations

PT (2)