Ketamine Analgesia in Third Molar Surgery

NCT04459377 | Completed Phase 4

• 2 other identifiers: 20140929sketamine2014-004235-39
• Study Type: interventional
• Target: 168
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pain; Postoperative

Keywords

Ketamine; Postoperative; Pain management; Third molar

Outcome Measures

Primary Outcomes (1)

• Pain (VAS)

  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 Outcomes (1)

• Safety (Oxygen saturation)

  Up to 2 hours.

Study Arms (3)

Placebo

PLACEBO COMPARATOR

Sodium Chloride solution (9mg / ml) 0.2ml / kg slow intravenous injection (2ml / min).

Drug: Sodium Chloride 0.9% Inj

K1

ACTIVE COMPARATOR

S-Ketamine (0.125 mg / kg body weight). (0.625mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).

Drug: S-Ketamine

K2

ACTIVE COMPARATOR

S-Ketamine (0.25 mg / kg body weight). (1.25mg / ml x 0.2ml / kg) slow intravenous injection (2ml / min).

Drug: S-Ketamine

Interventions

S-Ketamine DRUG

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.

K1; K2

Sodium Chloride 0.9% Inj DRUG

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 44 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy or mild well-compensated systemic disease (ASA I \& II)
• \<45 years
• kg body weight

You may not qualify if:

• 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

Sponsors & Collaborators

• Dalarna County Council, Sweden: lead
• Uppsala University: collaborator
• Center for Clinical Research Dalarna, Sweden: collaborator

Study Sites (1)

Käkkirurgiska kliniken, Falu lasarett

Falun, Dalarna County, 79182, Sweden

Location

Related Publications (1)

• Eriksson LB, Larsson A, Eriksson M, Tegelberg A, Thor A, Gordh T. Methodological comparison between salivary and plasma inflammatory biomarkers in third molar surgery patients. BMC Oral Health. 2025 Nov 22;25(1):1902. doi: 10.1186/s12903-025-07368-2.

  PMID: 41272580 DERIVED

MeSH Terms

Conditions

Pain; Agnosia

Interventions

Esketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Perceptual Disorders; Neurobehavioral Manifestations; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Lars Sand, Professor, DDS, MD

  Uppsala University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant in Oral and Maxillofacial Surgery

Study Record Dates

• First Submitted: July 1, 2020
• First Posted: July 7, 2020
• Study Start: February 14, 2017
• Primary Completion: March 10, 2022
• Study Completion: September 30, 2022
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)