Clinical trial NCT03035942: Quality of Recovery After Dexamethasone, Ondansetron or Placebo Intrathecal Morphine Administration
Official title: Role of Dexamethasone or Ondansetron in the Quality of Recovery After Intrathecal Morphine Administration in Patients Undergoing Lower Limb Surgery.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fractures, Bone
Nausea and Vomiting, Postoperative
Pruritus
Morphine Adverse Reaction
Satisfaction, Personal
Keywords: Intrathecal morphine
Nausea and vomiting
Quality of recovery
Patient satisfaction
Pruritus
Postoperative pain
Lead sponsor: Pontificia Universidade Catolica de Sao Paulo
Sponsor class: OTHER
First posted: 2017-01-30
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, controlled, double-blinded
Primary purpose: PREVENTION

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).

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.

Primary outcomes:
measure: Quality of Recovery
timeFrame: Twenty four hours after surgery by a blinded investigator
Secondary outcomes:
measure: Nausea and Vomiting During PACU Staying
timeFrame: 4h
measure: Number of Participants With Pruritus
timeFrame: 24 hours
measure: Pain During Postanesthesia Care Unit and Ward Stay (Numeric Rating Scale - NRS)
timeFrame: 24 hours
Other outcomes:
Locations:
city: Sorocaba
country: Brazil
facility: Santa Lucinda Hospital
state: SP
Study officials:
affiliation: PUC São Paulo University
name: Eduardo T Moro, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jacobson L, Chabal C, Brody MC, Ward RJ, Wasse L. Intrathecal methadone: a dose-response study and comparison with intrathecal morphine 0.5 mg. Pain. 1990 Nov;43(2):141-148. doi: 10.1016/0304-3959(90)91066-R.
citation: Slappendel R, Weber EW, Dirksen R, Gielen MJ, van Limbeek J. Optimization of the dose of intrathecal morphine in total hip surgery: a dose-finding study. Anesth Analg. 1999 Apr;88(4):822-6. doi: 10.1097/00000539-199904000-00026.
citation: Koju RB, Gurung BS, Dongol Y. Prophylactic administration of ondansetron in prevention of intrathecal morphine-induced pruritus and post-operative nausea and vomiting in patients undergoing caesarean section. BMC Anesthesiol. 2015 Feb 17;15:18. doi: 10.1186/1471-2253-15-18.
citation: Braga AA, Frias JA, Braga FS, Poterio GB, Hirata ES, Torres NA. Spinal anesthesia for cesarean section. Use of hyperbaric bupivacaine (10mg) combined with different adjuvants. Rev Bras Anestesiol. 2012 Nov-Dec;62(6):775-87. doi: 10.1016/S0034-7094(12)70178-2.
citation: Krajnik M, Zylicz Z. Understanding pruritus in systemic disease. J Pain Symptom Manage. 2001 Feb;21(2):151-68. doi: 10.1016/s0885-3924(00)00256-6.
citation: Griffiths JD, Gyte GM, Paranjothy S, Brown HC, Broughton HK, Thomas J. Interventions for preventing nausea and vomiting in women undergoing regional anaesthesia for caesarean section. Cochrane Database Syst Rev. 2012 Sep 12;2012(9):CD007579. doi: 10.1002/14651858.CD007579.pub2.
citation: Wu JI, Lo Y, Chia YY, Liu K, Fong WP, Yang LC, Tan PH. Prevention of postoperative nausea and vomiting after intrathecal morphine for Cesarean section: a randomized comparison of dexamethasone, droperidol, and a combination. Int J Obstet Anesth. 2007 Apr;16(2):122-7. doi: 10.1016/j.ijoa.2006.11.004. Epub 2007 Feb 1.
citation: Szarvas S, Chellapuri RS, Harmon DC, Owens J, Murphy D, Shorten GD. A comparison of dexamethasone, ondansetron, and dexamethasone plus ondansetron as prophylactic antiemetic and antipruritic therapy in patients receiving intrathecal morphine for major orthopedic surgery. Anesth Analg. 2003 Jul;97(1):259-63, table of contents. doi: 10.1213/01.ane.0000066310.49139.2a.
citation: Myles PS, Weitkamp B, Jones K, Melick J, Hensen S. Validity and reliability of a postoperative quality of recovery score: the QoR-40. Br J Anaesth. 2000 Jan;84(1):11-5. doi: 10.1093/oxfordjournals.bja.a013366.