Clinical trial NCT06595329: Comparison Between Epidural Analgesia and Intrathecal Opioid Analgesia for Pain Management in Open Nephrectomy
Official title: Comparison Between Epidural Analgesia and Intrathecal Opioid Analgesia for Pain Management in Open Nephrectomy: Prospective Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pain
Renal Cancer
Surgical Procedure, Unspecified
Keywords: Pain management
open nephrectomy
renal cell carcinoma
Lead sponsor: University Hospital of Split
Sponsor class: OTHER
First posted: 2024-09-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, single-center, randomized controlled trial. The study will take place in the University Hospital of Split, Departments of Anesthesiology, Reanimatology and Intensive Care Medicine, and the Department of Urology.

Patients undergoing open radical or partial nephrectomy for renal cancer will be randomized to one of the two groups: Epidural analgesia (Control) or intrathecal opioid (Intervention) group. Physiologic functions (blood pressure, heart rate, peripheral oxygen saturation) will be monitored during and after the surgery. Postoperatively, pain scores at rest as well as during movement will be recorded. A total dose of intraoperative opioids, time to first rescue analgesic, and total dose of rescue analgesics as well as adverse effects during the first 72 hours postoperatively will be recorded. These parameters will be compared between the two groups.
Primary purpose: TREATMENT

Brief summary: Nephrectomy is a surgical procedure of choice for patients suffering from renal cell carcinoma (RCC). Even though the laparoscopic approach is considered to cause fewer complications and reduce hospital stay, open surgery is still often performed. Open nephrectomy causes significant acute postoperative pain, and it can also lead to the development of chronic postoperative pain. Pain management is important for the overall recovery of patients undergoing major surgery such as open nephrectomy and it is a part of the enhanced recovery after surgery (ERAS) program.

In this prospective randomized clinical study, we plan to compare two different approaches to pain management regarding the level of acute pain (first 72 hours), side effects, systemic analgesics consumption, and hospital stay.

Our hypothesis are that intrathecal opioid administration significantly reduces acute postoperative pain compared to epidural analgesia in patients undergoing open radical or partial nephrectomy. We also hypothesize that the intrathecal opioid administration is associated with a lower incidence of adverse effects compared to epidural analgesia and shorter ICU length of stay.

Detailed description: This is a prospective, single-center, randomized controlled trial. The study will take place in the University Hospital of Split, Departments of Anesthesiology, Reanimatology and Intensive Care Medicine, and the Department of Urology.

Patients undergoing open radical or partial nephrectomy for renal cancer will be randomized to one of the two groups: Epidural analgesia (Control) or intrathecal opioid (Intervention) group. Physiologic functions (blood pressure, heart rate, peripheral oxygen saturation) will be monitored during and after the surgery. Postoperatively, pain scores at rest as well as during movement will be recorded. A total dose of intraoperative opioids, time to first rescue analgesic, and total dose of rescue analgesics as well as adverse effects during the first 72 hours postoperatively will be recorded. These parameters will be compared between the two groups.

Data sources:

Patient records (electronic and paper), direct measurements of patients' physiologic functions (perioperatively, during first 72 hours postoperatively), pain assessment at rest, and movement (Numerical rating scale (NRS)).

Ways of collection of data:

Direct measurements will be used for physiologic functions (change in heart rate and blood pressure). NRS questionnaire will be used to measure pain at rest and during movement in the first 72 hours. Patient records will be used for demographic data and to measure side effects of the received treatment and length of ICU and hospital stay.

Measurements will be conducted by anesthesiologists in the operating room, staff in the ICU during the period we are investigating (72 hours after the procedure) and researchers going through patients' records.

The population represented by the sample:

Patients scheduled for open radical or partial nephrectomy due to RCC.

Independent variables:

Demographic data (age, gender, weight), comorbidities, chronic medication, chronic pain medication, American Society of Anesthesiologists (ASA) score, duration of surgery, duration of anesthesia, baseline NRS score.

Intervention group:

Patients with RCC undergoing open nephrectomy randomized into a group receiving intrathecal morphine.

Control group:

Patients who will receive epidural analgesia will be treated as a control group given that epidural analgesia is the most favorable analgesic technique in accordance with ERAS protocol for major abdominal surgeries.

Tehnique of randomisation:

Participants will be randomly divided into two groups in a 1:1 ratio. Randomization will be performed using a computer program. A research coordinator will be designated to distribute and preserve randomization results.

Patients with RCC undergoing open nephrectomy will be asked to sign written informed consent before the enrolment should they choose to participate in this study. They will be instructed on how to self-assess pain severity via the numeric rating scale before surgery (NRS, an 11-point scale where 0 = no pain and 10 = most severe pain).

Treatment/intervention:

Patients undergoing open radical or partial nephrectomy will randomly receive either epidural analgesia or intrathecal morphine.

Patients in the Intervention group will receive a single dose of 300 mcg of morphine intrathecally before induction to general anesthesia. For patients in the control group, an epidural catheter will be placed before induction to the anesthesia. A local anesthetic (levobupivacaine 0.25%) will be administered as a bolus dose during the surgery and continuously (0.125% levobupivacaine) during the first 24 hours postoperatively. After the intervention, patients will undergo general anesthesia.

Changes in heart rate, blood pressure, and the total dose of opioids administered are going to be measured intraoperatively. After the procedure, patients are going to be admitted to the intensive care unit in the Urology department. In the first 72 hours we will be measuring pain at rest using the Numerical rating scale (NRS), pain during cough using NRS, time of the first rescue analgesia, total dose of additional analgesics during 72 hours postoperatively, and the incidence of adverse effects (hypotension, bradycardia, nausea, vomiting, pruritus, respiratory insufficiency). We will analyze the quality of recovery and time to gastrointestinal function recovery. Complications of intervention will also be noted: accidental dural puncture, post-dural puncture headache, failed block, unintentional intravascular injection of local anesthetic, and local anesthetic toxicity. Length of ICU and hospital stay will also be measured. Patients will be exposed to intervention before the surgery, epidural catheter will be extracted after 24 hours. The expected duration of the study is one/two year/s.

Eligibility criteria: Inclusion Criteria:

* Adult patients over the age of 18, scheduled for an open radical or partial nephrectomy due to RCC.
* American Society of Anesthesiologists (ASA) physical status classification I-III.

Exclusion Criteria:

* Patients who refuse to participate in this study.
* Patients with BMI \> 35 kg/m2 or \< 15 kg/m2.
* Patients with renal dysfunction (eGFR \<15 or requirement of renal replacement therapy), liver dysfunction (Child-Pugh class C), and heart failure (NYHA IV).
* Patients with ASA physical status classification ≥ IV.
* Patients with contraindication for the interventions planned for in this study (allergies to anesthetic drugs used in this study, coagulation disorders, and infection at the injection site).
* Patients with chronic opioid dependence.
* Patients unable to communicate preoperatively due to severe dementia, language barrier, or neuropsychiatric disorder.
* Patients for whom it is impossible to carry out the aforementioned interventions for technical reasons.

Primary outcomes:
measure: NRS score at 24 hours postoperatively
timeFrame: 24 hours
Secondary outcomes:
measure: Intraoperative opioid consumption
timeFrame: Intraoperatively.
measure: Numeric rating scale (NRS) score at 1, 3, 6, 48 and 72 hours postoperatively
timeFrame: 72 hours.
measure: Time to first rescue analgesia postoperatively
timeFrame: In the first 72 hours postoperatively.
measure: Total amount of rescue analgesia during 24 and 72 hours postoperatively
timeFrame: 72 hours.
measure: Incidence of adverse effects
timeFrame: 72 hours.
measure: Duration of procedure performance
timeFrame: During procedure execution (epidural catether placement, intrathecal administration of the drug).
measure: Gastrointestinal function recovery
timeFrame: Up to 72 hours post operatively.
measure: Hospital length of stay
timeFrame: Through study completion, an average of 1 year.
measure: ICU length of stay
timeFrame: Through study completion, an average of 1 year.
Other outcomes:
Locations:
city: Split
country: Croatia
facility: Univeristy Hospital of Split
Study officials:
affiliation: UH Split
name: Svjetlana Došenović, MD Phd
role: PRINCIPAL_INVESTIGATOR
References: