Closed Non Comminuted Long Bone Fractures Clinical Trial
Official title:
Efficacy of Continuous Intravenous Infusion vs. Scheduled Dosing of Lornoxicam on Patient Controlled Morphine Consumption After Orthopaedic Surgery: A Comparative Placebo Study
Perioperative continuous infusion of lornoxicam would be an effective and safe regimen to
reduce the patient controlled morphine consumption after orthopaedic surgery.
After ethical approval, 96 patients scheduled for elective orthopaedic fracture surgery under
general anaesthesia were randomly allocated to receive placebo, 12-hourly iv lornoxicam 16 mg
or lornoxicam 16 mg followed with continuous infusion of 1.3 mg/hr., for 48 hours after
surgery (n=32 per group). Anaesthesia was induced with propofol, sufentanil and rocuronium,
and was maintained with 0.5-1 minimum alveolar concentration sevoflurane, sufentanil and
rocuronium. Postoperative patient controlled morphine analgesia was used. Changes in heart
rate, mean blood pressure and sevoflurane minimum alveolar concentration, visual analogue
pain scores, and cumulative patient controlled morphine consumptions and blood loss for 48
hours, platelet functions, bone non-union and the presence of adverse effects were recorded.
An independent investigator who was not involved in the study instructed the patients
preoperatively about the use of visual analogue scale to assess the severity of postoperative
pain (0 mm for no pain and100 mm for worst imaginable pain) and about the use of PCA for
their postoperative pain management.
Anaesthetic management was standardized. Oral lorazepam 2 mg was given the night before
surgery. Subjects were allocated randomly into three groups (n = 32 for each) by drawing
sequentially numbered sealed opaque envelopes containing a software-generated randomization
code (Random Allocation Software, version 1.0.0, Isfahan University of Medical Sciences,
Isfahan, Iran)into the placebo, scheduled, and continuous infusion groups. The syringes
containing placebo and lornoxicam solutions were masked by identical opaque identical cover
sheets. The test solution was prepared by one anaesthesiologist before induction of
anaesthesia. Another anaesthesiologist, who was blinded to the study solution, gave the
anaesthetic and was instructed to avoid using local anaesthetics, and a third
anaesthesiologist collected perioperative data. All staff in the operating room were unaware
of patient allocation group.
Patient monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry,
end-tidal sevoflurane and carbon dioxide (ETCO2) concentrations, response entropy (RE) and
state entropy (SE.
After preoxygenation for 3 min, anesthesia was induced with fentanyl 1 - 3 µg/kg, propofol
1.5-2.5 mg/kg (to achieve an SE <50 and a difference<10 between RE and SE; RE-SE) and
rocuronium 0.6 mg/kg. Tracheal intubation or slipping of laryngeal mask appropriate for body
weight were used according to the discretion of the attending anaesthetist. Anaesthesia was
maintained with a 0.6-1 minimum alveolar concentration of sevoflurane (MAC-Sevo) with air in
40% oxygen and fentanyl 1 µg/kg boluses to maintain SE <50 and RE-SE <10 and heart rate and
mean arterial blood pressure within 20% of their baseline values. Rocuronium 0.1 mg/kg was
given to maintain suppression of the second twitch using a train-of-four stimulation. The
patients' lungs were ventilated to maintain an ETCO2 of 30-35 mmHg. Sevoflurane were
discontinued at the start of skin closure, residual neuromuscular block was antagonized and
the trachea extubated.
Postoperative analgesia was achieved according to the hospital protocol with patient
controlled morphine analgesia (1 mg/ml), 1 mg, with a lockout interval of 8 minutes and a
maximum 24-hourly limit of 180 mg. respiratory depression defined as the decrease in
respiratory rate below 8/min was treated with i.v naloxone 0.2 mg. Nausea and vomiting were
treated with i.v granisetron 1 mg and pruritus was treated with i.m promethazine 25 mg.
Heart rate and mean arterial blood pressure were recorded before (baseline) and 10 min after
the start of infusion; every 30 min during surgery; every 15 min during the stay in post
anaesthesia care unit (PACU), and 8 hourly for the following 48 hours. MAC-Sevo was recorded
every 15 min after intubation until the end of surgery. Intraoperative fentanyl consumption
was recorded.
The VAS pain scores, the presence and intensity of postoperative sedation (four-point verbal
rating scores (VRS): awake, drowsy, rousable or deep sleep), nausea and vomiting (0: no
nausea; 1: nausea no vomiting; 2: nausea and vomiting), were reported every 15 min for the
first postoperative hour and two-hourly thereafter for the first 48 postoperative hours. The
cumulative morphine consumption during the first 24 and 48 postoperative hours were recorded.
Platelet function assay was performed before and every 24 hrs. for the first three days after
surgery. Cumulative intraoperative and postoperative blood loss and the number of transfused
blood units were recorded. The presence of fracture non-union was reported.
All patients were observed by an independent investigator during the study period for the
presence of nausea, vomiting, gastritis, reflux esophagitis, headache, bleeding,
bronchospasm, sweating, allergy, thrombocytopenia, bleeding, ecchymosis, or increases in
liver transaminases.
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