Quality of Recovery After Dexamethasone, Ondansetron or Placebo Intrathecal Morphine Administration

NCT ID: NCT03035942

Last Updated: 2020-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-01-02
• Study Completion Date: 2019-11-04

Brief Summary

The aim of this study is to evaluate not only the occurrence of side effects, but the quality of the recovery (QoR-40 Questionnaire) of patients submitted to spinal anesthesia with administration of low doses (0.1 mg) of intrathecal morphine for the surgical treatment of fractures in one of the lower limbs and who will receive prophylactic ondansetron (4mg), dexamethasone (8mg) or placebo.

Detailed Description

This randomised, double-blinded trial was approved by the Research Ethics Committee of the School of Medical and Health Sciences, Pontifical Catholic University of São Paulo (Sorocaba, São Paulo - Brazil), on June 14 2016, CAAE (Presentation Certificate for Ethical Appreciation) 58208015.7.0000.5373 (Chairperson Prof. J.A. Costa). On the day of surgery, after completion of the pre-anesthetic evaluation and due explanations of the study, consent will be obtained. No participant will take any pre-anesthetic medication before surgery. Subjects will be randomised using a computer-generated (www.random.org) table of random numbers into 3 groups: S (saline), D (dexamethasone 8 mg), or O (ondansetron 4 mg). Group assignments will be sealed in sequentially numbered opaque envelopes that were opened after patient inclusion in the study. All care providers, researchers, and patients will be blinded to group assignments. Study 5-mL syringes will be prepared by a nurse independent of the study. Normal saline (5 mL total volume), dexamethasone (made up to 5 mL with normal saline), or ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened.

After arrival in the operating room, standard ASA (American Society of Anesthesiologists) monitors will be applied. Immediately after venoclysis,e.v. midazolam will be administered as titrated doses to achieve 3 or 4 on Ramsay scale. Spinal puncture will be performed with the patient in the seated position in the median or paramedian line at L3-L4 or L2-L3 interspace using a 26-gauge Quincke needle. Anesthesia will be established with a single bolus of 0.5% hyperbaric bupivacaine (17.5 mg if ≥ 70 kg or expected surgery duration > 150 minutes and 15 mg if < 70 kg) and preservative-free morphine 0.1 mg. Normal saline will be used for fluid replacement therapy. In case of failure of spinal anesthesia, the technique will be repeated or a general approach will be performed and the patient will be excluded from the study. Titrated doses of midazolam (up to 10 mg) or propofol continuous infusion will be administered to achieve perioperative sedation (≥4 on Ramsay scale). Supplemental oxygen 5 L/min via a vent mask will be administered during and after surgery.

Postanesthesia care unit (PACU) All patients will be transferred to the PACU. Data related to the occurrence of pain, nausea, vomiting, pruritus, urinary retention and time to Aldrete score ≥ 9 at the PACU will be recorded. Pain will be assessed every 15 minutes using a 0-10 numeric pain rating scale (NRS), where zero meant no pain and 10 the worst imaginable pain. Morphine (1 to 2 mg) was administered intravenously every 10 minutes to maintain the pain score below 4 (1 mg when the pain score was <7 and 2 mg when it was ≥7). Postoperative nausea and vomiting (PONV) will be treated with dimenhydrinate (30 mg) intravenously. Pruritus will be classified as follow: 0 - no symptoms, 1 - 3 - mild symptoms, 3 - 7 moderate symptoms and 7 - 10 - severe symptoms. Nalbuphine 5 mg intravenously will be administered when score > 4.

Ward Following discharge from the PACU (minimum stay 60 minutes and Aldrete score ≥ 9), all of the participants were given ketoprofen (100 mg) every 12 hours and dipyrone (30 mg.kg-1, maximum 1 g) every six hours intravenously. Whenever patients judged that their analgesia was insufficient, tramadol (100 mg) was administered intravenously at eight-hour minimum intervals as needed. Postoperative nausea and vomiting (PONV) were treated with dimenhydrinate (30 mg) intravenously. An investigator who was blinded to group assignment collected all postoperative outcome data 24 hours after surgical procedure. Subjects were asked to rate the higher score of pain (NRS) during the hospital ward stay. Tramadol consumption, occurrence of urinary retention and the number of nausea and vomiting episodes were also recorded. These findings were confirmed with the ward nursing staff. All subjects stayed at hospital for at least 24 hours.

Data Collection The baseline QoR-40 questionnaire was completed by the subjects after informed consent was obtained in the preoperative holding area and 24 hours after surgery by a blinded investigator. The QoR-40 questionnaire evaluates five dimensions of recovery (physical comfort - 12 items; emotional state - 7 items; physical independence - 5 items; physiological support - 7 items; and pain - 7 items). Each item was rated on a five-point Likert scale: none of the time, some of the time, usually, most of the time, and all the time. The total score on the QoR-40 ranges from 40 (very poor quality of recovery) to 200 (best quality of recovery).

The primary outcome of interest will be the QoR-40 score on postoperative day 1 (POD1).

Conditions

Fractures, Bone; Nausea and Vomiting, Postoperative; Pruritus; Morphine Adverse Reaction; Satisfaction, Personal

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

D Group

Dexamethasone 8 mg

Group Type: EXPERIMENTAL

Dexamethasone

Intervention Type: DRUG

Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.

O group

Ondansetron 4 mg

Group Type: EXPERIMENTAL

Ondansetron

Intervention Type: DRUG

Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.

S group

Normal saline (5 mL total volume)

Group Type: PLACEBO_COMPARATOR

Saline

Intervention Type: DRUG

Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.

Interventions

Dexamethasone

Dexamethasone 8 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.

Intervention Type: DRUG

Ondansetron

Ondansetron 4 mg (made up to 5 mL with normal saline) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.

Intervention Type: DRUG

Saline

Normal saline (5 mL total volume) will be drawn into each syringe which will be offered to the anesthesia provider after the opaque envelope was opened and administered immediately after spinal anesthesia was performed.

Intervention Type: DRUG

Other Intervention Names

D Group; O Group; Placebo Group

Eligibility Criteria

Inclusion Criteria

• ASA physical status I or II, who will scheduled to undergo surgical treatment of lower limb fractures

Exclusion Criteria

Patients who:

(i) refused to participate in the study;

(ii) were not able to communicate due to alterations in the level of consciousness, or neurologic, or psychiatric disease;

(iii) presented with contraindication to any of the drugs used in the present study;

(iv) had history of alcohol or drug abuse and

(v) had surgery in the last 10 days were excluded.

Reasons for exclusion after randomisation will be protocol violations or if the anesthesia technique was changed from a spinal to a general approach.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pontificia Universidade Catolica de Sao Paulo

OTHER

Sponsor Role: lead

Responsible Party

Eduardo Toshiyuki Moro

Assistant Professor, MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eduardo T Moro, Professor

Role: PRINCIPAL_INVESTIGATOR

PUC São Paulo University

Locations

Santa Lucinda Hospital

Sorocaba, São Paulo, Brazil

Countries

Brazil

References

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Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

PUCSP 1863886

Identifier Type: -

Identifier Source: org_study_id