Combined Intravenous Dexamethasone and Dexmedetomidine as Adjuncts to Popliteal and Saphenous Nerve Blocks in Patients Undergoing Orthopaedic Surgery of the Foot and Ankle (ADJUNCT2)

Zealand University Hospital

Status and phase: Completed; Phase 4

Conditions: Anesthesia, Local

Treatments: Drug: Dexamethasone 12 mg; Drug: Saline; Drug: Dexamethasone 12 mg + dexmedetomidine 1 mcg/kg

Study type: Interventional

Funder types: Other

Identifiers

NCT04818749

ADJUNCT2

Details and patient eligibility

About

The investigators will investigate the beneficial and harmful effects of combining dexamethasone (12 mg) and dexmedetomidine (1mcg/kg) as adjuncts to popliteal and saphenous nerve blocks in patients undergoing surgery of their foot or ankle.

Full description

This is a randomised, blinded, placebo-controlled, multicentre, parallel, 3-arm clinical trial assessing the effects of adjunct intravenous dexamethasone + dexmedetomidine 1mcg/kg versus intravenous dexamethasone 12mg versus intravenous placebo on time to first pain (i.e. block duration) in patients undergoing surgery of the foot or ankle. All participants will receive a sciatic and saphenous nerve block and general anesthesia.

The investigators will randomise participants to either intervention arm. Participants will be allocated according to a computer-generated random allocation sequence with random permuted blocks and stratification by site. The allocation will be concealed in sequentially numbered opaque envelopes that will not be opened before the participant has been allocated to that specific allocation number/envelope. Trained trial personnel not otherwise involved in the trial will prepare the trial medication according to the allocation.

All others involved will be blinded for the entire duration of the trial (participant, carers, investigators, people delivering the intervention, observers/outcome assessors, statisticians). Blinding will not be broken until agreement has been reached within the steering committee regarding the statistical analysis. The trial medication is prepared in identical syringes with 20ml of identically appearing trial medication. The syringes are subsequently marked with 'syringe 1' and 'syringe 2' and delivered to the investigators. Syringe 1 either contains 12mg dexamethasone or saline and will be administered prior to block performance using an infusion pump set to deliver the volume over 12 minutes. Syringe 2 either contains 1 mcg/kg dexmedetomidine or saline and will be administered after block performance and general anesthesia over 30 minutes using an infusion pump, thereby masking the sedative effect of the dexmedetomidine. The investigators will not be present in the operation room during surgery.

The investigators expect little to no attrition bias since the intervention is simple with a short follow-up. The investigators expect some missing data for duration of the motor block, as most participants will have the affected limb immobilized post-surgery, thereby making assessment of return of motor function difficult.

The statistical analysis plan was pre-defined prior to unblinded data becoming available and can be found on: https://doi.org/10.6084/m9.figshare.22491214.

Enrollment: 120 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Scheduled for unilateral osseous surgery of the ankle or foot
• General anaesthesia with both a popliteal and a saphenous nerve block for postoperative analgesia
• Age of 18 or above
• American Society of Anaesthesiologists Physical Status Score of 1 to 3
• Body Mass Index of 18 to 40, but a minimum weight of 50 kg.
• For fertile women, negative urine humane choriongonadotropine test and use of safe anti-conception
• Ability to understand the trial protocol, risks, benefits, and provide signed informed consent

Exclusion criteria

• Inability to read and understand Danish
• Uncooperativeness (as judged by investigators)
• Participation in another trial involving medication
• Allergy to study medication
• Daily use of opioids above 30 mg/day morphine (or equivalents)
• Daily use of corticosteroids of more than 5 mg prednisolone equivalents within the past one month
• Neurological or musculoskeletal disease making block performance impossible (as judged by investigators)
• Dysregulated diabetes (as judged by investigators)
• Dysregulated anticoagulants (as judged by investigators)
• History of drug or alcohol abuse
• Glaucoma
• Contraindications for paracetamol or opioids
• Contraindications to general anaesthesia
• Other concomitant conditions needing surgery
• Other concomitant traumatic injuries

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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120 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

Participants allocated to this arm will have placebo administered intravenously before block performance and placebo administered intravenously after induction of general anaesthesia.

Treatment:

Drug: Saline

Dexamethasone 12 mg

Active Comparator group

Description:

Participants allocated to this arm will have dexamethasone 12 administered intravenously before block performance and placebo administered intravenously after induction of general anaesthesia.

Treatment:

Drug: Dexamethasone 12 mg

Dexamethasone 12 mg + dexmedetomidine 1 mcg/kg

Experimental group

Description:

Participants allocated to this arm will have dexamethasone 12 administered intravenously before block performance and dexmedetomidine 1 mcg/kg administered intravenously after induction of general anaesthesia.

Treatment:

Drug: Dexamethasone 12 mg + dexmedetomidine 1 mcg/kg