Programmed Intermittent Bolus Erector Spinae Plane Block vs Programmed Intermittent Bolus Epidural Analgesia in Acute Pain Management after Major Abdominal Surgery: A Randomized Controlled Trial

Faculty Development Competitive Research Grant Program (General) 2024-2026

Acute postoperative pain is one of the major issues in the postoperative period that may lead to negative patient experience and can also results in different complications, such as cardiovascular, pulmonary, neurologic, and metabolic derangement [1]. Postoperative analgesia mostly employ a multimodal approach to minimize the side effects of analgesics, enhance pain relief and recovery [1-3]. Inadequate perioperative pain management has been consistently reported to result in complications such as ileus, delayed mobilization, lengthened hospital stays, and even chronic pain [1-4]. Recent studies demonstrated that fewer than 50% of patients undergoing major surgeries received satisfactory pain relief and suffered postoperative pain [4]. Opioids are one of the most commonly prescribed drugs for postoperative pain control. Although they are highly efficacious drugs for severe postoperative pain, they cause multiple side effects, such as nausea& vomiting, gastrointestinal and bladder dysfunction, respiratory depression, drowsiness, respiratory depression [2-6]. Opioids can delay early mobilization and discharge from the medical centers, which is a significant issue in hospitals with high patient volume [2-6].
Several methods of regional anesthesia have been studied and are successfully used in postoperative pain control [7-15]. Epidural analgesia (EA) has been one of the most common methods of postoperative analgesia for various types of abdominal surgeries. It is often referred to as the preferred method for alleviating pain following surgical procedures on the abdominal wall [16,17]. EA has been has been one of the most common methods of postoperative analgesia for various types of abdominal surgeries. EA has been used with good results with regards to decreasing opioid requirements and pulmonary complications. Epidural catheters are not without risk, however. Numerous complications, including failure to provide analgesia, hypotension, epidural hematomas and others are rare [16,17].
Therefore, there is a need to look for alternatives that will improve postoperative pain management. Several regional anesthesia techniques including ESPB have been developed and successfully used after abdominal surgical procedures. Despite development of newer regional anesthesia techniques, EA is still by far the most frequently used method for pain management after major abdominal surgery in Kazakhstan. Programmed intermittent bolus (PIB) is an emerging approach to manage postoperative pain. It is characterized by automated boluses at regular intervals and injection volumes and is believed to provide high infusion pressure for the efficient spread of anesthetics in the epidural space [19]. We suppose that PIB might be a promising technique for better maintenance of both ESPB and EA.
Since PIB-ESPB and PIB-EA have not been directly compared yet, we aim to conduct a randomized controlled clinical trial to compare their safety and efficacy in major abdominal surgery.
Inclusion Criteria:
1.Male and Female patients aged 18-70 years - body mass index less 35 kg/m2
2.Major upper abdominal surgeries performed through midline abdominal incisions (Whipple's procedure, gastrectomy, open hemicolectomy, major debulking gynaecological surgery)
3. American Society of Anesthesiologists physical status class I - III
4. Signed informed consent;
Exclusion criteria
1. Coagulation disorder;
2. Infection at the site of injection;
3. Allergy to local anesthetics;
4. Advanced heart, liver, or renal failure;
5. Chronic drug use;
6. Obesity, body mass index (BMI) ≥ 35 kg m−2;

Patient randomization
Patients will be randomized at the time of enrollment into the trial to receive either PIB-ESPB or PIB-EA using 1:1 allocation. The randomization process will be performed by an independent assistant by a random number generator schema with allocation being concealed from the main study investigators. The investigators of the surgical team and the acute pain service team will be informed of which group the patient is assigned to.
Blinding
All patients and outcome assessors will be masked (blinded) to the patient group. The medications will be prepared by an anesthesiologist who is not involved in evaluation of patient outcomes. Both solutions will externally appear identical. Unmasking will take place only after statistical analysis has been completed.
Sample size calculation
We plan to test non-inferiority of PIB-ESPB to PIB-EA using a continuous primary outcome measurement of NRS pain scores and secondary outcomes (described later). Using data from recent trials that measured pain scores, we estimated that the standard deviation for NRS (range 1-10 points) would be approximately 1.5. We selected a non-inferiority limit of 1.0 point, below which we considered that the mean difference in scores would not likely be clinically significant. For example, if the mean NRS score for PIB-ESPB was 3.0 with a standard deviation of 1.5 points, we could declare PIB-ESPB non-inferior to PIB-EA if the PIB-ESPB had a mean NRS score of 4.0 or less. In other words, if PIB-ESPB is non-inferior to PIB-EA, then 50 patients per group are required to be 90% sure that the lower limit of a one-sided 95% confidence interval (or equivalently a 90% two-sided confidence interval) will be above the non-inferiority limit of -1. This takes into account a loss to follow-up rate of up to 20%.
Anesthesia
In the operating room (OR), standard anesthesia monitoring with electrocardiography (EKG), non-invasive blood pressure (NIBP), peripheral oxygen saturation (SpO2) and bi-spectral index monitoring (BIS monitoring) will be applied to all patients. After the insertion of a 22-gauge intravenous line, a 15 mL kg−1 normal saline infusion will be started. The anesthesiologists will perform induction into anesthesia with intravenous propofol 2–3 mg kg−1, analgesia-fentanyl 1 μg kg−1 and myorelaxation - rocuronium bromide 0.6 mg kg−1, and when the patients' BIS scores reduces to 40–60, tracheal intubation will be performed. Maintenance of anesthesia will be performed with total intravenous agents: propofol I.V., low-dose ketamine infusion, fentanyl.
Study interventions
Following tracheal intubation, patients in the PIB-ESPB group will be placed in the lateral decubitus position. The investigator-anesthesiologist will place the ultrasound probe in longitudinal orientation at the level of the T7 spinous process and then move the probe 3 cm laterally from the midline. The ultrasound landmarks, which included the T7 transverse process and the overlying erector spinae muscle, will be identified. Under aseptic conditions, a 80-mm 21-gauge block needle (Stimuplex(R) B-Braun medical, Melsungen, Germany) will be inserted in-plane at an angle of 30–40° in cranial-to-caudal direction until the tip contacted the T7 transverse process. After hydro-dissection with 2–3 mL of isotonic saline solution anesthesiologist will confirm the correct needle tip position, then the anesthesiologist will advance the catheter deep to the erector spinae muscle. The same procedure will be repeated on the contralateral side. After surgery, the PIB-ESPB catheter will be connected to a PCA pump ((CADD-Solis ambulatory infusion pump, Smith Medical, St Paul, MN, USA). The pump will be connected to the ESP block catheter containing 300 mL of 0.2% ropivacaine. All the patients will receive a loading dose of 0.2% ropivacaine 15 mL via the ESP block catheter. Ropivacaine will then be administered as a bolus of 8 mL every hour over 80 s. The PCA pumps will be programmed to deliver 5 mL patient-controlled boluses with a lockout interval of 30 min.


In the second group, patients will receive thoracic epidural analgesia at the T7 level via a standard approach. At the end of surgery, a 5-mL initial dose of local anesthetic (ropivacaine 2 mg will be administered via the epidural catheter after surgery. A pump (CADD-Solis ambulatory infusion pump, Smith Medical, St Paul, MN, USA) will be used. The pump will deliver the local anesthetic at a dose of 5.1 mL every 90 min. The PCA system will be programmed to deliver a 3-mL bolus of the local anesthetic with a lockout interval of 15 min in both groups.
All routes of postoperative opioid usage will be converted to total parenteral morphine equivalents for both groups and tallied for each postoperative day. Utilization of non-opioid pain medications including acetaminophen and ketorolac will be also recorded. Intravenous fluid resuscitation will be performed in a goal-directed manner, utilizing benchmarks of urine output of 0.5 mL/kg/hr, systolic blood pressure <90 mm Hg, and heart rate >100 beats/min. Fluid administration will be guided by an on-call intensivist.
Outcomes
Primary outcome and measurement
The primary outcome of this study will be the pain scores after initial stabilization. The pain will be assessed at 3, 6, 12, 18, 24, and 48 hours after end of surgery. We will test the non-inferiority of IPB-ESPB relative to and IPB-EA for this outcome.
Pain scores will be assessed using the patient-reported numeric rating scale (NRS) -where 0 is no pain and 10 the worst pain possible.
Secondary outcomes and measurement
The following secondary outcomes will be measured during the in-hospital stay:
1.Total opioid consumption (morphine or equivalents) in hospital for analysis will be measured (from the end of surgery up to 48 hours).
2. Incidence post-operative complications:
a) Post-operative nausea and vomiting (PONV) Score : 1 to 3 (1- No nausea, 2- Nausea, 3- Vomiting)
b) Respiratory depression will be evaluated by continuous monitoring of SpO2;
c) Local anesthetic toxicity (LAST) will be monitored based on clinical symptoms, signs, hemodynamic monitoring.
3.Quality of sleep (Pittsburgh Sleep Quality index)
4.Physiological parameters (blood pressure, pulse, arterial oxygen saturation) during first 24 hours while the patient is in ICU.
5. Overall patient satisfaction at discharge (using a 7-item Likert scale)
6.Postoperative cognitive dysfunction (will be assessed at 12, 24, 48, 72 hours)
8.Postoperative delirium (will be assessed at 12, 24, 48, 72 hours)