Clinical trial NCT05078372: Ropivacaine and Midazolam by Intraarticular vs Epidural Administration in Arthroscopic ACL
Official title: Comparison of the Effectiveness of the Use of Ropivacaine and Midazolam by Intraarticular vs Epidural Administration on Post-operative Analgesia After Isolated Arthroscopic ACL Reconstruction With Hamstring Autograft.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anterior Cruciate Ligament Injuries
Anesthesia Injection Site
Knee Injuries
Keywords: Knee infiltration
Anterior Cruciate Ligament
Hamstring
Ropivacaine
Midazolam
Lead sponsor: Universidad Autonoma de Nuevo Leon
Sponsor class: OTHER
Collaborators: name: Universitat Autonoma de Barcelona
First posted: 2021-10-14
Enrollment: 108
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Two study groups will be generated, each consisting of 54 research subjects, randomly each recipient will receive epidural anesthesia with or without intraarticular ropivacaine. The group to which the patient belongs will be assigned through a computer program, the patient will not know to which group he belongs or what medication he will receive. The patients will be extracted from the external traumatology clinic
Primary purpose: TREATMENT

Brief summary: Compare of the effectiveness of the use of ropivacaine and midazolam by intraarticular vs epidural administration on post-operative analgesia after isolated arthroscopic anterior cruciate ligament (ACL) reconstruction with hamstring autograft.

Detailed description: Anterior cruciate ligament (ACL) reconstruction is a common surgical knee procedure that presents moderate to severe postoperative pain, additionally, an adequate control of the pain is required to start intensive rehabilitation after the surgery, early hospital discharge and reduction of the administration of oral and intravenous anesthetic drugs.

Postoperative pain is a common upsetting symptom following ACL reconstruction that delay return to daily activity of the patient and leads to an increase in days of hospitalization and early rehabilitation.(Harris et al., 2014) Therefore, pain is also mediated by free nerve endings in the knee joint, which are located in the tendons of semitendinosus, gracilis and sartorius muscles, associated with higher pain in comparison with ACL allograft.(Hong et al., 2019) For effective, safe and longer post-ACL reconstruction analgesia, several analgesic strategies such as systemic medication, central or peripheral blocks, and intra-articular drug administration have been used to control the pain. (Baverel et al., 2016; Dauri et al., 2003; Parker et al., 2007; Peng et al., 2018; Zhou et al., 2016; Zou et al., 2016) Combined spinal anesthesia is better option for knee surgery, it can reduce the disadvantages of general and alone spinal or epidural anesthesia. Combined spinal anesthesia appears to be effective and with lower toxicity than general anesthesia. (Baldawi et al., 2020; Johnson et al., 2016; Moucha et al., 2016; Padwal et al., 2019) Moreover, reduce the hospital stay and extends the analgesia into the postoperative period without increasing morbidity. (Johnson et al., 2016)

HYPOTHESIS: The hypothesis was that there are differences in the quality and quantity of postoperative pain in knee arthroscopy surgery when midazolam plus ropivacaine is administered epidurally, in comparison to ropivacaine and midazolam by intraarticular.

Methodology:

Type of study: Controlled clinical trial. Study design: Experimental, longitudinal, comparative, prospective and double blind.

Approximate duration of the study: 12 months Population type and sample size: A total of 108 patients undergoing elective surgery for anterior cruciate ligament reconstruction after rupture Research Site: Patients will be recruited from Consultation No. 15 of the Orthopedics and Traumatology Service of the University Hospital "Dr. José Eleuterio González "of the U.A.N.L. Surgeries will be carried out in the Department of Surgical Therapeutics on the 5th floor of the University Hospital of the U.A.N.L.

Randomization mode: 108 sealed envelopes are prepared prior to the start of the study, which will include the group to which the patient will belong. The patient will not know the group to which he will belong until the moment of revealing the final results of the study.

Recruitment Methodology: Each patient who is admitted to the elective surgery of ACL reconstruction will be invited to participate voluntarily in the study. The principal investigator or one of the co-investigators will be responsible for thoroughly explaining the details of the study, including the potential benefits and risks, as well as answering any questions that may arise, if the patient agrees to participate, the patient will be asked to sign the informed consent in the presence of two witnesses and a note will be made in the clinical file where the inclusion in the study will be recorded, in the same way a copy of the consent will be given to the patient. For the purpose of the study, the identification of the patient will not be necessary only his gender, age, height and weight. The study population will be divided into 2 groups: 1. Ropivacaine plus midazolam by intra-articular application and Group 2: Ropivacaine plus midazolam epidural administration.

The surgeries of all the groups will be performed with the same surgical technique, using a total primary ACL reconstruction with TighRope ® Endobutton system. The patients will be operated by 2 subspecialists in hip joint surgery, professors of the Orthopedics and Traumatology Service of the University Hospital "Dr. José Eleuterio González "as the main surgeon and as surgical assistants to the resident doctors of Orthopedics and Traumatology.

Anesthesia protocol There were used combined spinal-epidural anesthesia. The patient was placed in lateral decubitus position. Under aseptic technique, the intervertebral space between L2-L3 or L3-L4 was superficially infiltrated with 2% lidocaine. The lumbar spinal level was identified with an 18-gauge Tuohy needle included in the spinal-epidural combined kit (Espocan®, B Braun, Germany). After that, a Whitacre 25 spinal needle was placed and the anesthesiologist confirmed the correct position by the free flow of cerebrospinal fluid. 7.5 mg (1.5 ml) of 0.5% hyperbaric bupivacaine were administered. Thereafter an epidural catheter was introduced, about 4 cm into the epidural space through the Tuohy needle for maintenance anesthesia and 60 mg (3 ml) of lidocaine with 2% epinephrine were administered to ensure the correct position outside a blood vessel. In case of prolongation of the surgical time, the anesthetic effect was extended through the epidural catheter.

Once the surgical procedure was completed and depending on the group to which the patient belongs, postoperative analgesia was administered.

Group 1. Ropivacaine with intra-articular midazolam. Ropivacaine 0.75% at 1.5 mg / kg (Ropiconest®, PiSA, Mexico) was used with midazolam at 50 mcg / kg kg (Ralecum®, PiSA, Mexico), to complete 20 ml of solution and was administrated on the knee articulation after tourniquet release. And an elastomeric pump (Home Pump® of 5 ml / hr for 24 hours) was prepared for epidural infusion, with 150 ml of physiological solution.

Group 2. Ropivacaine plus epidural midazolam. An elastomeric pump (Home Pump® of 5 ml / hr for 24 hours) was prepared for epidural infusion. This was prepared with 150 mg (20 ml) of 0.75% ropivacaine plus midazolam at 50 mcg / kg / 12 hrs. The solution was made up to 125 ml with physiological solution. Moreover, 20 ml of physiological solution, was intraarticular administered as placebo in the Ropivacaine plus epidural midazolam group.

Surgical technique All patients underwent an arthroscopic ACL reconstruction with ipsilateral hamstring autograft. There were used tourniquet in all the procedures, with the patient in supine position, with lateral positioner to perform valgus on the knee. Lateral and medial standard portals were used. A diagnostic arthroscopy was realized in all cases to check the menisci and the knee cartilage. After that the semitendinosus and gracilis tendon were harvested by a 2 cm anteromedial incision.

Repairable tears of meniscus were treated with all-inside an outside-in sutures technique. Irreparable meniscal tears were managed with partial meniscectomy and were stabilized with shaving and radio frequency cauterization of the meniscus remnant.

Drug administration protocol:

The sealed envelope will be opened on the preoperative day to identify which experimental group the patient belongs In the first group will receive an elastomeric pump was prepared for epidural infusion, with 150 ml of physiological solution and ropivacaine 0.75% at 1.5 mg / kg was used with midazolam at 50 mcg / kg kg to complete 20 ml of solution and was administrated on the knee articulation after tourniquet release.

The second group An elastomeric pump was prepared for epidural infusion. This was prepared with 150 mg (20 ml) of 0.75% ropivacaine plus midazolam at 50 mcg / kg / 12 hrs. The solution was made up to 125 ml with physiological solution. Moreover, 20 ml of physiological solution, was intraarticular administered as placebo.

The protocol for the pre and post-operative administration of the drugs will be as follows:

Only one author knew about the drugs that were administrated. The drugs were prepared in unlabeled syringes as the same volume and were recorded separately by a co-investigator who was not involved in the analysis of the study. Also, this physician, were involved in the surgery and performed anesthetic care. A blinded investigator, who was not involved in the anesthetic care of the patients, collected all study data. Surgeon, anesthesiologist and rehabilitator were blinded to group allocation.

Intrahospital follow-up Each patient was given a logbook and asked to self-evaluate and record pain (according to the 10-point VAS) before and 15 min after an analgesic administration. In case of pain with a VAS greater than 4, , 1g of acetaminophen and 30 mg IV of ketorolac were administrated. For higher than 7 points 50 mg IV of Tramadol was indicated, in any of the 2 groups, which could be repeated every 6 hours if required. In the case of the need for rescue analgesia, tramadol 50 mg IV, 30 mg IV of ketorolac and 1 g of acetaminophen were administered, the time in postoperative hours in which the first dose was administered and the total number of doses administered in 24 hours was documented, as well as the performance of equianalgesic conversion of opioids for the necessary dose used for rescue analgesia, taking into account that 200 mg IV / day of tramadol is equal to 20 mg IV / day of morphine, considered as the main reference for opioid analgesics. Tramadol 400 mg / day should not have been exceeded.

All patients who presented nausea received ondansetron 4 mg perioperative. Supplemental doses of ondansetron 1 mg were administered at the first indication of moderate to severe nausea.

Patient's discharge It will be discharged by medical indication to the patient 48 hours after surgery, if there is no type of contraindication, with indications of discharge in medical prescription and follow-up by the external consultation after one week.

Eligibility criteria: Inclusion Criteria:

1. Age over 18 years and younger than 50 years
2. Arthroscopic single bundle anterior cruciate ligament anatomic reconstruction with hamstring tendon autograft
3. Unilateral procedure
4. With or without meniscal tear
5. Desire to participate voluntarily in the study and signature of informed consent
6. Pre-operative assessment with result between (American Society of Anesthesiologist) ASA I or ASA II performed and annexed in the clinical file either by the Department of Internal Medicine, Cardiology or Anesthesiology.

Exclusion Criteria:

1. Another ligament surgery (posterior cruciate ligament, medial collateral ligament, posterolateral corner reconstruction)
2. ACL reconstruction with allograft
3. Bone to bone or quadriceps autograft
4. ACL reconstruction with double bundle technique
5. Patients with previous knee surgeries
6. Open ACL reconstruction
7. Corrective knee osteotomy or articular cartilage repair surgery, meniscal transplant, lateral extraarticular tenodesis
8. Pregnant or lactating patients
9. Patients under 18 years old
10. Patients consuming oral contraceptives
11. Patients who present any contraindication for neuraxial blockade (e.g., coagulation defects, infection at the puncture site, pre-existing neurological deficits in the lower extremities, Anticoagulant or antiplatelet therapy that has not been suspended 48 hours before the surgery, systemic infection, fever above 38.5º)
12. Preoperative assessment with ASA III-IV
13. Hypersensitivity to the drugs used in the study
14. Patients with intellectual impairments or psychiatric conditions that limited adequate communication
15. Patients with a diagnosis of fibromyalgia, polymyalgia rheumatica, complex painful syndromes or sciatic neuropathy

Primary outcomes:
measure: Post-operative analgesic request
timeFrame: will be measured at 24 hours after surgery
Secondary outcomes:
measure: Therapeutic effect on visual analog scale
timeFrame: Pain will be measured at 2, 6, 12 , 24 and 48 hours after surgery.
measure: Side effects of analgesic drugs
timeFrame: Hemoglobin levels will be measured at 2, 6, 12 , 24 and 48 hours after surgery.]
measure: Postoperative range of motion
timeFrame: at 24 and 48 hours after surgery.]
measure: Post-operative analgesic request
timeFrame: will be measured at 2, 6, 12 , 24 and 48 hours after surgery.
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Universidad Autonoma de Nuevo Leon
state: Nuevo LEON
Study officials:
affiliation: University Hospital "Dr. José Eleuterio González", Universidad Autonoma de Nuevo León (U.A.N.L.)
name: Rodolfo Morales-Avalos, MSc, MD
role: PRINCIPAL_INVESTIGATOR
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