Quality of Recovery After Dexamethasone, Ondansetron or Placebo Intrathecal Morphine Administration
Condition: Fractures, Bone; Nausea and Vomiting, Postoperative; Pruritus; Morphine Adverse Reaction; Satisfaction, Personal
MeSH terms: Pruritus; Nausea; Vomiting; Postoperative Nausea and Vomiting; Fractures, Bone
Study type: Interventional
Phase: Phase 4

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).
    

Intervention name(s): Dexamethasone; Ondansetron; Saline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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.
Other intervention name(s): D Group; O Group; Placebo Group
Intervention MeSH terms: Dexamethasone; Ondansetron
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Prospective, randomized, controlled, double-blinded
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Intrathecal morphine; Nausea and vomiting; Quality of recovery; Patient satisfaction; Pruritus; Postoperative pain