Role of Dexamethasone or Ondansetron in the Quality of Recovery After Intrathecal Morphine Administration in Patients Undergoing Lower Limb Surgery.
Phase: PHASE4
Conditions: Fractures, Bone, Nausea and Vomiting, Postoperative, Pruritus, Morphine Adverse Reaction, Satisfaction, Personal
Sponsor: Pontificia Universidade Catolica de Sao Paulo

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 
NCT03035942 
June 1st 2016 
 
Study protocol 
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 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 (ondansetrona 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 ondansetrone 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 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. Titraded 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. 
 
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). 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 POD1.