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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Pain

Intervention / Treatment
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* Drug: Dexamethasone
* Other: Placebo
* Drug: Morphine
* Drug: Zofran
* Drug: Paracetamol
* Drug: Ibuprofen


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pain, Analgesia, Postoperative, Dexamethasone, Spine surgery