This study is designed as a single-center, prospective, double-blinded, randomized controlled trial. The participants will be randomly assigned to either the anterior QLB group or the placebo group.
This study was approved by the institutional review board of Yokohama City University Hospital (B180405008) and was registered with the UMIN Clinical Trials Registry (UMIN000032255, registered on April 15, 2018). This trial will be performed according to the principles of the Declaration of Helsinki (Edinburgh 2000 version). Written informed consent will be obtained from each participant before enrollment.
A pharmacist (SA) will provide a set of 140 random numbers for the allocation sequence using a website (http://www.randomiza tion.com). None of the investigators, except for the pharmacists will be aware of the block size. The random allocation sequence will only be available to pharmacists, and thus, it will be concealed from the other research team members. The included participants will be randomly assigned to either the anterior QLB group or the placebo group in a ratio of 1:1.
The pharmacists in the Department of Pharmacy of Yokohama City University Hospital will prepare the syringes containing either 30 mL of 0.25% levobupivacaine (Maruishi Pharmaceutical Co., Tokyo, Japan) or 30 mL of normal saline in accordance with the allocation sequence. The syringes will be labeled “trial drug” and given a number, and will be transported into the operating rooms by the drug conveyance responsible in the hospital. The pharmacists in the Department of Pharmacy will participate in the trial only at this stage; therefore, the participants, attending anesthesiologist, surgeons, evaluators, as well as the researchers will be unaware of the random allocation sequence. The random allocation sequence will not be exposed until the final data analysis report is completed.
This trial will be conducted in the Yokohama City University Hospital (3-9, Fukuura, Kanazawa-ku, Yokohama city, Japan).
Patients eligible for the study must comply with all of the following criteria at randomization:
・Elective unilateral total hip arthroplasty;
・Age ≥20 years;
・American Society of Anesthesiologists Physical Status (ASA-PS) 1–2;
・Written informed consent to participate in this trial.
・Liver and kidney dysfunction (aspartate aminotransferase >80 IU/L, alanine aminotransferase >80 IU/L, estimated glomerular filtration rate <50 mL/min);
・Coagulopathy (prothrombin time/international normalized ratio >1.50, activated partial thromboplastin time >60 sec);
・Body mass index >35;
・Strong opioid use, such as morphine or fentanyl;
・Allergy to the study drugs and their components;
・Cases judged to be inappropriate by the researchers. For instance, cases where the patient has undergone other femoral surgeries such as intramedullary nailing.
Since certain patients with hip osteoarthritis receive tramadol for management of their pain in Japan, we decided to include these patients in our trial, and exclude those receiving strong opioids such as morphine or fentanyl.
General anesthesia induction and maintenance
Upon arrival to the operating room, a standard vital monitoring system, which includes electrocardiography equipment, non-invasive blood pressure monitor, and pulse oximeter, will be installed and a 22- or 20-gauge intravenous catheter will be inserted in the patient’s forearm. General anesthesia will be induced with propofol 1.5 mg/kg, fentanyl 3 μg/kg, and rocuronium 0.6 mg/kg; tracheal intubation will be performed. General anesthesia will be maintained using desflurane 3%–5% and remifentanil 0.2 μg/kg/min. The concentration of desflurane and additional use of rocuronium will be left to the discretion of the attending anesthesiologist. If the patient’s blood pressure increases to more than 20% of the baseline blood pressure during surgery, the anesthesiologist will administer fentanyl 50–100 µg and observe the patient for 15 min. On the contrary, if the blood pressure decreases to less than 20% of the baseline blood pressure, the anesthesiologist will administer ephedrine 4–8 mg or phenylephrine 0.05–0.1 mg and observe the patient for 15 min. The attending anesthesiologist will measure the blood pressure every 5 minutes; in cases with further decline, additional administration of ephedrine or phenylephrine will be permitted.
Anterior QLB procedure
After general anesthesia induction, anterior QLB will be performed in the lateral position. A low-frequency convex probe for the abdomen (2–5 MHz convex probe, Sonosite Edge ® rC60xi; Sonosite Canada Inc. Markham, Ontario, Canada) will be placed horizontally above the iliac crest. On ultrasound, the lumbar vertebral body and transverse process appear as “thumbs up” structures. Additionally, three muscles can be found around the transverse process: the psoas major, erector spinae, and quadratus lumborum muscles. The psoas major is located on the ventral side of the transverse process; the erector spinae is located on the dorsal side of the transverse process; and the quadratus lumborum is located on the lateral side of the transverse process.
After a pre-scan and ultrasound parameter optimization, the probe will be applied using a sterile technique. A 20-gauge short bevel needle (Visioplex, Vygon, France) will be inserted in the plane from the posterior edge of the convex probe through the quadratus lumborum in an anteromedial direction. When the needle tip reaches the area between the psoas major and the quadratus lumborum, 30 mL of 0.25% levobupivacaine will be injected in the anterior QLB group; the same amount of normal saline will be injected in the placebo group. Figure 1 shows an ultrasound image of anterior QLB.
The procedures of anterior QLB will be performed by the attending anesthesiologists under the guidance of either one of the experts in ultrasound-guided peripheral nerve blocks (MK, YM, HF, and TN). Confirmation by at least two anesthesiologists should ensure that the quality of anterior QLB is maintained.
We will observe whether any complications related to the perioperative procedures, including surgical and anesthetic complications occur until the end of the trial. Our clinical trial will be performed within the scope of health insurance; the costs of treatment in participants who experience potential harm will therefore be covered.
Perioperative management of pain and PONV
As multimodal analgesia, 20 mg/kg acetaminophen (maximum 1000 mg/body) will be administered after the end of surgery and repeated each 6 hours until 24 hours. From postoperative day 1 to 7, the patients will receive celecoxib 100 mg twice a day. Intravenous fentanyl will be used for patient-controlled analgesia (IV-PCA) using CADD-solis (Smiths Medical, Grasbrunn, Germany). A bolus injection of 10 mg fentanyl with a 10-min lockout time may be administered for analgesia; continuous infusion of fentanyl will not be considered. In our clinical experience, the pain in most patients may be managed with this protocol. If the patients experience pain, particularly before they start drinking-water, flurbiprofen axetil or diclofenac sodium will be administered during the postoperative period. However, in our clinical experience, the incidence of flurbiprofen axetil or diclofenac sodium administration is considerably low.
To prevent PONV, dexamethasone 6.6 mg will be administered before the start of the surgery. Droperidol 0.02 mg/kg or metoclopramide 10 mg may be used according to the postoperative condition. Repeated administration of droperidol and metoclopramide will be permitted in patients continuing to experience PONV.