Does the Preoperative Midazolam Dose Affect Postoperative Pain?

NCT ID: NCT03534895

Last Updated: 2018-05-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

168 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-05-31

Study Completion Date

2020-08-31

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.

Conditions

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Pain, Postoperative

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

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PC1

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

Group Type PLACEBO_COMPARATOR

Normal saline

Intervention Type OTHER

intravenous

Spinal anesthesia

Intervention Type PROCEDURE

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

Surgery

Intervention Type PROCEDURE

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

Postoperative analgesia

Intervention Type DRUG

IV acetaminophen 1g + IV ketorolac 30mg

Rescue analgesia

Intervention Type DRUG

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

Wound infiltration

Intervention Type DRUG

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

Analgesia at home

Intervention Type DRUG

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

PC2

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

Group Type EXPERIMENTAL

Midazolam Injectable Solution

Intervention Type DRUG

intravenous

Normal saline

Intervention Type OTHER

intravenous

Spinal anesthesia

Intervention Type PROCEDURE

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

Surgery

Intervention Type PROCEDURE

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

Postoperative analgesia

Intervention Type DRUG

IV acetaminophen 1g + IV ketorolac 30mg

Rescue analgesia

Intervention Type DRUG

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

Wound infiltration

Intervention Type DRUG

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

Analgesia at home

Intervention Type DRUG

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

PC3

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

Group Type EXPERIMENTAL

Midazolam Injectable Solution

Intervention Type DRUG

intravenous

Normal saline

Intervention Type OTHER

intravenous

Spinal anesthesia

Intervention Type PROCEDURE

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

Surgery

Intervention Type PROCEDURE

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

Postoperative analgesia

Intervention Type DRUG

IV acetaminophen 1g + IV ketorolac 30mg

Rescue analgesia

Intervention Type DRUG

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

Wound infiltration

Intervention Type DRUG

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

Analgesia at home

Intervention Type DRUG

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

Interventions

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Midazolam Injectable Solution

intravenous

Intervention Type DRUG

Normal saline

intravenous

Intervention Type OTHER

Spinal anesthesia

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

Intervention Type PROCEDURE

Surgery

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

Intervention Type PROCEDURE

Postoperative analgesia

IV acetaminophen 1g + IV ketorolac 30mg

Intervention Type DRUG

Rescue analgesia

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

Intervention Type DRUG

Wound infiltration

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

Intervention Type DRUG

Analgesia at home

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

Intervention Type DRUG

Other Intervention Names

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Dormicum

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Centro Hospitalar de Entre o Douro e Vouga

OTHER

Sponsor Role collaborator

Centro Hospitalar de Vila Nova de Gaia/Espinho

OTHER

Sponsor Role collaborator

Universidade do Porto

OTHER

Sponsor Role lead

Responsible Party

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Caroline Dahlem

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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Centro Hospitalar Entre Douro e Vouga, EPE

Santa Maria da Feira, , Portugal

Site Status

Centro Hospitalar Vila Nova de Gaia / Espinho, EPE

Vila Nova de Gaia, , Portugal

Site Status

Countries

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Portugal

Central Contacts

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Caroline Dahlem, MD

Role: CONTACT

+351968061851

Facility Contacts

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Caroline Dahlem, MD

Role: primary

Carmen Oliveira, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 6121598 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10323274 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 23314164 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10861157 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24882605 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11037766 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21188440 (View on PubMed)

Other Identifiers

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Midazolam RCT

Identifier Type: -

Identifier Source: org_study_id

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