Ketamine Analgesia in Third Molar Surgery
An Analysis of Ketamine Analgesia in Third Molar Surgery -Effects, Safety and Influence on Inflammatory Biomarkers in Plasma
BACKGROUND AND PURPOSE Outpatient surgery (day case surgery) is increasing. When the patients go home on the same day, this demands safe pain relief. A reduction of morphine (opioid) use is sought because of side effects and the dependency risk. An effective alternative to opioids is ketamine, which lacks the side effects of opioids but provides powerful analgesic effects.
METHOD At the start of surgery, Ketamine or placebo will be given in a vein to evaluate if the acute pain decreases significantly. Inflammation is known to cause pain. By measuring different proteins in the blood, the investigators want to understand how inflammation links to the pain. Wisdom tooth surgery provides significant post-operative pain and is a widely accepted pain model in drug studies. Patients referred for wisdom tooth surgery are asked to participate in the study. For statistical certainty, in total 165 persons will be enrolled to three groups. Two with active drug (different dose) and one placebo. Everyone gets local anesthesia. The completion of the study will be done in four years. The Ethics Review Board has approved the study.
CLINICAL RELEVANCE Effective pain relief after daily surgical procedures is important for patient´s safety and reducing the risk of long-term pain. It is also ethically necessary for the continued expansion of day case surgery. New knowledge of the mechanisms of pain increases the opportunities for individual and safe pain relief. Day case surgery is performed in all operating specialties, this might affects many patients nationally and internationally.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Dalarna
-
Falun, Dalarna, Sweden, 79182
- Käkkirurgiska kliniken, Falu lasarett
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy or mild well-compensated systemic disease (ASA I & II)
- 18- <45 years
- 50-100 kg body weight
Exclusion Criteria:
- Medication drugs: analgesics, hypnotics (the last week before surgery), thyroid hormones, psychoactive drugs or monoamine oxidase inhibitors (MAO inhibitors).
- Hypertension [> 150/95 mmHg in screening study]
- Heart failure
- Psychosis
- Epilepsy
- Hyperthyreosis
- Myasthenia gravis
- Glaucoma
- Verified sleep apnea
- Diabetes (insulin treated)
- Porphyria
- Pregnancy
- Breast-feeding
- Blood transmitted infections, such as HIV and hepatitis B and C
- Known hypersensitivity to midazolam, ketamine, ibuprofen, or local anesthetics
- Inability to obtain the requisite written or oral information
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Placebo Comparator: Placebo
Sodium Chloride solution (9mg / ml) 0.2ml / kg slow intravenous injection (2ml / min).
|
Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation. All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed. |
|
Active Comparator: K1
S-Ketamine (0.125 mg / kg body weight).
(0.625mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).
|
Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation. All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed. |
|
Active Comparator: K2
S-Ketamine (0.25 mg / kg body weight).
(1.25mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).
|
Patients are randomized to three groups. Randomization in blocks of six patients stratified by sex. A list of serial numbers and randomized group affiliation is produced which is open to the pharmacy's manufacturing staff and closed to the staff of the trial. The pharmacy prepares filled syringes with investigation drug in accordance with randomized group affiliation. All groups are sedated with midazolam intravenously to a defined end point. A syringe pump with volume accuracy ± 2% injects the test drug (P, K1 or K2). One infusion set is coupled between the syringe and a three-way connection, which in turn is connected to a peripheral venous catheter (PVK). This PVK is also used for blood sampling. Blood is sampled at two occasions. Directly preoperatively and two hours after surgery. The third molar is surgically removed. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Pain (VAS)
Time Frame: 4 hours postoperatively
|
Postoperative pain measured by Visual analog scale (VAS).
From minimum 0mm to maximum 100mm.
0mm is no pain and 100mm is worst pain imaginable.
Changes in Visual Analog Scale value from preoperatively to 4 hours postoperatively
|
4 hours postoperatively
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Safety (Oxygen saturation)
Time Frame: Up to 2 hours.
|
Change in oxygen saturation measured by pulseoximeter %.
Intra individually and between the groups.
From start to completion of the ketamine infusion.
|
Up to 2 hours.
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: Lars Sand, Professor, DDS, MD, Uppsala University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Psychotropic Drugs
- Antidepressive Agents
- Ketamine
- Esketamine
Other Study ID Numbers
- 20140929sketamine
- 2014-004235-39 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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