Ropivacaine and Midazolam by Intraarticular vs Epidural Administration in Arthroscopic ACL
Condition: Anterior Cruciate Ligament Injuries; Anesthesia Injection Site; Knee Injuries
MeSH terms: Wounds and Injuries; Knee Injuries; Anterior Cruciate Ligament Injuries
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): ropivacaine and midazolam intraarticular administration; ropivacaine and midazolam epidural administration
Intervention type(s): Drug; Drug
Intervention description(s): Patients undergoing ACL reconstruction with hamstring autograft who will receive ropivacaine and midazolam epidural administration for anesthesic technique for the procedure, and intraarticular administration of those drugs.; Patients undergoing ACL reconstruction with hamstring autograft who will receive ropivacaine and midazolam epidural administration for anesthesic technique for the procedure
Other intervention name(s): Ropiconest®; Ralecum®; Ropiconest®; Ralecum®
Intervention MeSH terms: Midazolam; Ropivacaine
Allocation: Randomized
Intervention model: Parallel Assignment
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
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Knee infiltration; Anterior Cruciate Ligament; Hamstring; Ropivacaine; Midazolam