DOI: 10.5281/zenodo.10407181
title: Comparative study between Dexmedetomidine with Bupivacaine and Bupivacaine alone in erector spinae plane block for postoperative pain control of posterior lumbosacral spine fixation surgeries: A randomized controlled trial

description: 2. Materials and Methods

2.1. Participants

Patients above 18 years old of either sex submitted for elective posterior lumbosacral spine fixation and fusion surgery were eligible to participate if they were classified as ASA I-III according to the American Society of Anesthesiologists (ASA) classification. The surgery was done on all the patients by the same neurosurgical team and using the same surgical techniques. The exclusion criteria included patient refusal, hypersensitivity to the drugs used in the study, patients with any contraindication to regional anesthesia, such as skin infections at the site of the block, and patients with a history of bleeding disorders or receiving anticoagulant medications. All patients were screened for eligibility criteria. Eligible patients were asked for voluntary informed consent to participate in the trial.

2.2 Study design

This double-blind, randomized controlled trial was carried out on 90 patients on October 6 University Hospitals. It was conducted from November 2022 to July 2023. The study was approved by the Clinical Research Ethical Committee of October 6 University Hospitals (approval number PRC-Me-2210035). It was registered online at ClinicalTrials.gov Identifier: NCT05590234. All patients who participated in this study had to sign a detailed, informed, written anesthesia and surgery consent. 

2.3. Randomization and allocation 

Patients were randomly allocated using a random allocation sequence by a web-based program. Participants were randomized to three groups in a 1:1:1 ratio. Each group consisted of 30 patients. Dexmedetomidine Bupivacaine ESPB group (DB group) receive 0.5 ug/kg dexmedetomidine plus 20 mL of bupivacaine 0.25%, Bupivacaine ESPB group (B group) receive 20 mL of bupivacaine 0.25%, and Saline ESPB (S group) which is the Control group receive 20 ml of normal saline 0.9%. The block procedure was done bilaterally in the three groups. Neither patients nor investigators knew the group in which the patients were placed, and the type of intervention received.

2.4. Preoperative management

All patients were assessed clinically before surgery, including full history, thorough clinical examination, and laboratory investigations. On arrival at the operating suite, patients were fully monitored (5 leads ECG, noninvasive blood pressure, and pulse oximetry). Basal readings of vital data were recorded. Intravenous access was established.

2.5. Anesthetic management

Midazolam 3 mg IV was given for sedation. Induction of anesthesia was performed with IV propofol (2mg/kg), fentanyl (1.5–2 µg/kg), and rocuronium bromide (0.6 mg/kg). Maintenance of anesthesia was done by isoflurane. The prone position was established immediately after the intubation of anesthesia. Intraoperatively, the data of (peripheral oxygen saturation, heart rate, noninvasive arterial blood pressure, and end-tidal carbon dioxide level) were recorded every five minutes throughout the operation. 

Any decrease in heart rate below 50 beats per minute was treated with intravenous atropine, according to the response. A reduction in mean blood pressure below 20% of the basal reading or systolic BP below 90 mmHg was treated with 5 mg increments of intravenous ephedrine. After the induction of anesthesia and putting the patients in the prone position, the US-guided ESPB was performed in the three groups.

The study was conducted in a double-blind fashion where the attending anesthetist who performed the ESPB and the neurosurgical team were blind entirely to the content of the injected solution composition. The responsible anesthetist in this study was the only one not blind to the injected solution composition but was not involved in the postoperative patient assessment.  

             2.6. ESPB technique

Under strict aseptic technique, the ESPB was done in the prone position for all patients of the three groups. A sterile ultrasound curved probe (Philips ultrasound machine HD7 XE C153160013, Philips and Neusoft Medical Systems Co., Ltd. China.) was used for the technique. The ultrasound probe was placed on the third lumbar vertebral body level in the parasagittal plane. When the spinous process was first seen, the probe was moved laterally from the midline, and then the transverse process of L3 and erector spinae muscle was observed at about 2 to 3 cm from the midline (Figure 1). 

A 22 gauge/ 8 cm ultrasound-visible needle (Stimuplex, Braun AG, Melsungen, Germany) was used to make a puncture using the in-plane technique. The direction of the needle was craniocaudal, and the proper position of the needle was confirmed by injecting 2 ml of saline solution. After ensuring the position of the needle, 20 ml of 0.25% bupivacaine plus 0.5 ug/kg dexmedetomidine was administered to the DB group. The same ESPB procedure was done on the other side with the same drugs and volume. In total, 40 ml of 0.25% bupivacaine plus 1 ug/kg dexmedetomidine was administered.

The same block procedure was done in the B group with only 20 ml of 0.25% bupivacaine on both sides (with a total volume of 40 ml). In the S group (control group), the same block procedure was done with 20 ml of 0.9% normal saline on both sides (40 ml total volume).

 

 

 

 

Figure 1. Ultrasound image of ESPB.

 

At the end of surgery, 1 gm of paracetamol IV and 30 mg of ketorolac IV infusion were given to all the patients of the three groups. The patients were extubated after efficient spontaneous breathing and transported to the post-anesthesia care unit (PACU). Patients were discharged from the PACU to the ward with a modified Aldrete score of 12.

2.7. Postoperative pain management

The postoperative analgesic management was done using the classical protocol of our department to all patients of the three groups, which included a PCA (patient-controlled analgesia) device, and an IV of one gm paracetamol was given every eight hours for the first 48 hours postoperatively. The PCA device (Accufuser Plus ®REF, manufactured by Woo Young Medical Co., Ltd. Korea) has a silicon balloon infuser with a total volume of 300 ml, basal rate of 5 ml per hour, bolus 1 ml, and lockout interval every 15 minutes. 

A PCA device with morphine was attached to all the patients. The PCA infusion (300ml) consisted of 60 mg of morphine with 2 mg of granisteron and 180 mg of ketorolac. The concentration of morphine was set to 0.2 mg/ml, the loading dose was 1 mg (5 ml), the lockout interval was 15 min (bolus of 1ml/15 min), and a 1 mg/h (5ml/hr) continuous infusion was maintained for 48 hrs. IV one gm paracetamol was given every eight hours postoperatively.

A nurse blind to the study used the visual analog scale (VAS; zero, no pain, ten = the most severe pain) to evaluate and record the pain scores and recorded the opioid consumption of the patients. The nurse recorded passive (at rest) and active (while mobilization) VAS scores at intervals of every two hours in the first 24 hours and every 4 hours in the second 24 hours and total opioid consumption for the first 48 hours postoperatively. Rescue analgesic medication was done using pethidine 50 mg IM when passive VAS pain score > 6. 

Patients who experienced pruritis, nausea, vomiting, or respiratory depression (opioid-related adverse effects) were recorded. On the first day postoperative, all patients were encouraged to ambulate in the ward after wearing lumbosacral support. The subcutaneous closed suction drainage system was removed after 36 hours. All patients were discharged home after 48 hours.

2.8. Outcome measurements

The primary clinical outcome measures were active (while mobilization) and passive (at rest) visual analog scale (VAS) pain score at the first 48 hours, measured every 2 hours in the first 24 hours and every 4 hours in the second 24 hours. 

Other clinical outcomes included opioid consumption (the number of PCA presses), the need for rescue analgesia, postoperative opioid side effects, and intraoperative dexmedetomidine side effects such as bradycardia and hypotension.

2. 9. Sample size calculation 

As we have three treatment groups (S, B, DB), we performed a one-way analysis of variance (ANOVA) to assess effect size and the required number of patients per group based on the overall difference of total Fentanyl consumption (µg) means (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908442/).  The effect size for ANOVA is typically measured using Cohen's d = M1 - M2 / spooled, where spooled =&radic; [(s 12+ s 22) / 2] and effect-size r= d / √ (d2 + 4)[https://lbecker.uccs.edu/#means%20and%20standard%20deviations].  

Given the following values: 

·         Mean 1: 820 SD1: 102

·         Mean2: 641 SD2: 140

·         α=0.05

·         β=0.05 (implying a power of 0.95)

Then, Cohen's d: -1.46  &   effect-size r: -0.58

In addition, the required sample size per group is 17 based on the following online tool [https://homepage.univie.ac.at/robin.ristl/samplesize.php?test=anova] for sample size for one-way analysis of variance. 

2.10. Statistical analysis

Data were analyzed using the statistical package for social sciences, version 20.0 (SPSS Inc., Chicago, Illinois, USA). We conducted the Shapiro-Wilk test to assess whether the numeric data followed a normal distribution or not. Quantitative normal distributed data were expressed as mean± standard deviation (SD). Qualitative data were expressed as frequency and percentage. The following tests were used: A one-way analysis of variance (ANOVA) when comparing between more than two means, Post Hoc test: Least Significant Difference (LSD) was used for multiple comparisons between different variables, and Chi-square (X2) test of significance was used to compare proportions between two qualitative parameters. Furthermore, we performed linear and binary regression analyses to elucidate the relationship between the primary outcomes and the intervention groups (S, D, DB).

The confidence interval was set to 95%, and the margin of error accepted was set to 5%. So, the p-value was considered non-significant when the P-value > 0.05, significant if < 0.05, and highly significant if <0.001.