The Effect of Dexamethasone in Combination With Paracetamol and Ibuprofen on Postoperative Pain After Spine Surgery

The Effect of Dexamethasone in Combination With Paracetamol and Ibuprofen as Adjuvant, Postoperative Pain After Herniated Disc Surgery

The analgesic effect of dexamethasone is not well described, but studies have shown that dexamethasone can be a safe part of a multimodal analgesic strategy after surgery. Our purpose is to investigate if dexamethasone in combination with paracetamol and ibuprofen has an increased analgesic effect compared to paracetamol and ibuprofen alone, on postoperative pain after spine surgery. Our hypothesis is that dexamethasone can reduce postoperative pain and reduce opioidconsumption and side effects compared to placebo.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Drug: Dexamethasone; Drug: Morphine; Drug: Zofran; Drug: Paracetamol; Drug: Ibuprofen; Other: Placebo

Detailed Description

The analgesic effect of dexamethasone is not well described, but studies have shown that an intermediate dosis of dexamethasone (0.11-0.2 mg/kg) can be a safe part of a multimodal analgesic strategy after surgery. Dexamethasone has an opioid-sparing effect and reduces pain during rest and mobilisation. Our purpose is to investigate if dexamethasone in combination with paracetamol and ibuprofen has an increased analgesic effect compared to paracetamol and ibuprofen alone, on postoperative pain after herniated disk surgery. Our hypothesis is that dexamethasone can reduce postoperative pain and reduce opioidconsumption and side effects compared to placebo.

• Study Type: Interventional
• Enrollment (Actual): 160
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Glostrup, Denmark, 2600
    • Glostrup University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients undergoing lumbar disc surgery in general anaesthesia.
• Patients who have given their written consent to participate and understand the contents of the protocol.
• ASA 1-3.
• BMI > 18 og < 40.
• Fertile women need a negative HCG urine test.

Exclusion Criteria:

• Patients who cannot cooperate to the study.
• Patients who do not speak and/or understand Danish.
• Fertile women with a positive HCG urine test.
• Allergy to the drugs used in the trial.
• Alcohol or medicine abuse, assessed by investigator.
• Patients who have had spine surgery before.
• Daily use of strong opioids (morphine, ketobemidone, oxynorm, methadone, fentanyl)
• Daily oral steroid treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Dexamethasone; Intravenous administration of dexamethasone 16 mg (concentration 4 mg/ml, volume 4 ml) immediately after endotracheal intubation; Morphine. Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml.; Zofran 4 mg iv in case of moderate to severe nausea, supplemented by Zofran 1 mg iv if needed; Tablet Paracetamol 1 g orally and tablet Ibuprofen 400 mg orally. Both 1 hour preoperatively and every 6 hours after extubation time during the first 48 hours.	Drug: Dexamethasone; Intravenous administration of dexamethasone 16 mg (concentration 4 mg/ml, volume 4 ml) immediately after endotracheal intubation; Drug: Morphine; Morphine. Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml.; Drug: Zofran; Zofran 4 mg iv in case of moderate to severe nausea, supplemented by Zofran 1 mg iv if needed; Drug: Paracetamol; Tablet Paracetamol 1 g orally, 1 hour preoperatively and every 6 hours after extubation time during the first 48 hours.; Drug: Ibuprofen; Tablet Ibuprofen 400 mg orally, 1 hour preoperatively and every 6 hours after extubation time during the first 48 hours.
Placebo Comparator: Placebo; Intravenous administration of isotonic sodium chloride (concentration 9 mg/ml, volume 4 ml) immediately after endotracheal intubation; Morphine. Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml.; Zofran 4 mg iv in case of moderate to severe nausea, supplemented by Zofran 1 mg iv if needed; Tablet Paracetamol 1 g orally and tablet Ibuprofen 400 mg orally. Both 1 hour preoperatively and every 6 hours after extubation time during the first 48 hours.	Drug: Morphine; Morphine. Patient controlled intravenous morphine (PCA-pump), bolus 2.5 mg, lock-out-time 10 minutes. Concentration : Morphin 1 mg/ml.; Drug: Zofran; Zofran 4 mg iv in case of moderate to severe nausea, supplemented by Zofran 1 mg iv if needed; Drug: Paracetamol; Tablet Paracetamol 1 g orally, 1 hour preoperatively and every 6 hours after extubation time during the first 48 hours.; Drug: Ibuprofen; Tablet Ibuprofen 400 mg orally, 1 hour preoperatively and every 6 hours after extubation time during the first 48 hours.; Other: Placebo; Intravenous administration of isotonic sodium chloride (concentration 9 mg/ml, volume 4 ml) immediately after endotracheal intubation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Painscore during mobilization	Painscore during active mobilization (VAS scale) defined by a standarized movement from recumbent position to sitting on the bedside at time 2, 4, 8, 12 and 24 hours, calculated as area under curve (AUC) from 2-24 hours after extubation time.	2-24 hours after extubation time.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Painscore during rest	Painscore during rest (VAS scale) at time 2, 4, 8, 12 and 24 hours, calculated as area under curve (AUC) from 2-24 hours after extubation time.	2-24 hours after extubation time
Morphine consumption	Total morphine consumption 0-24 hours after extubation time, administered as patient controlled analgesia (PCA, bolus 2.5 mg, lockout 10 minutes).	0-24 hours after extubation time.
Painscore during rest and mobilization	Painscore during rest and during active mobilization (VAS scale) at time 48 hours after extubation time.	48 hours after extubation time
Degree of nausea	Degree of nausea 2, 4, 8, 12, 24 and 48 hours after extubation time	2, 4, 8, 12, 24 and 48 hours after extubation time
Incidence of vomiting	Total number of vomits 0-2, 2-4, 4-8, 8-12, 12-24 and 24-48 hours after extubation time.	0-2, 2-4, 4-8, 8-12, 12-24 and 24-48 hours after extubation time.
Zofran consumption	Consumption of Zofran (milligram) 0-24 and 24-48 hours after extubation time.	0-24 and 24-48 hours after extubation time.
Degree of sedation	Degree of sedation 2, 4, 8, 12, 24 and 48 hours after extubation time.	2, 4, 8, 12, 24 and 48 hours after extubation time.
Quality of sleep	Quality of sleep 24 hours after extubation time.	24 hours after extubation time.

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Glostrup University Hospital, Copenhagen
• Investigators: Principal Investigator: Rikke Soennichsen, MD, Glostrup University Hospital; Study Chair: Joergen B Dahl, MD, Rigshospitalet, Denmark

Publications and helpful links

General Publications

• Nielsen RV, Fomsgaard J, Mathiesen O, Dahl JB. The effect of preoperative dexamethasone on pain 1 year after lumbar disc surgery: a follow-up study. BMC Anesthesiol. 2016 Nov 16;16(1):112. doi: 10.1186/s12871-016-0277-z.
• Nielsen RV, Siegel H, Fomsgaard JS, Andersen JDH, Martusevicius R, Mathiesen O, Dahl JB. Preoperative dexamethasone reduces acute but not sustained pain after lumbar disk surgery: a randomized, blinded, placebo-controlled trial. Pain. 2015 Dec;156(12):2538-2544. doi: 10.1097/j.pain.0000000000000326.

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): August 1, 2014
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: September 26, 2013
• First Posted (Estimate): October 1, 2013

Study Record Updates

• Last Update Posted (Estimate): October 27, 2015
• Last Update Submitted That Met QC Criteria: October 26, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: Pain; Analgesia; Dexamethasone; Postoperative; Spine surgery
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Analgesics, Opioid; Narcotics; Dexamethasone; Acetaminophen; Morphine; Ibuprofen
• Other Study ID Numbers: SM-RS-2012; 2012-004181-18 (EudraCT Number)