Lung Cancer (Diagnosis)
Conditions
Keywords
Exparel®, Liposomal Bupivacaine, Multi-Level Intercostal Nerve Block, Serratus Anterior Plane Block, Robotic-Assisted Thoracic Surgery, Adult, Pulmonary Wedge Resection, Lobectomy, Pulmonary Segmentectomy, Pneumonectomy, Minimally-Invasive Thoracic Surgery, Pain Control, Regional Anesthetic Block
Brief summary
The goal of this clinical trial is to assess how the location of local anesthetic medication affects pain control capabilities in adult patients undergoing thoracic(chest)-only minimally invasive surgery. The main questions it aims to answer are: * Is pain decreased when local analgesia is provided as a combination of serratus anterior plane block and intercostal nerve block when compared to either block administered individually? * How does location of local analgesia administration impact length-of-stay, cost-of-care, and quality-of-life? Researchers will compare three treatment options including long-acting local anesthetic (Exparel®) administered as (1) intercostal nerve block, (2) serratus anterior plane block, or (3) combination of intercostal nerve block and serratus anterior plane block to see if pain and opioid use are reduced dependent upon treatment group. All participants will receive a local anesthetic nerve block. Participants will be asked to describe their pain after surgery and to answer various questionnaires before and after surgery.
Interventions
PROCEDUREArm 1 "LipoB-I": Liposomal Bupivacaine via Multi-Level Intercostal Nerve Block
The anesthetic mixture is prepared by combining 266 mg (20 mL) of Liposomal Bupivacaine (Exparel®) with 50 mg (20 mL) of 0.25% Bupivacaine Hydrochloride, creating a mixture of 40 mL. This mixture is administered via multi-level intercostal nerve block (ICNB). One injection is administered by a surgeon per intercostal space (ICS), given at the origin of the nerve space junction where the nerve and the inferior aspect of the rib meet after the nerve immerges from the intervertebral foramina. At least 5 mL, and no more than 8mL, will be injected in each ICS with the ideal injection consisting of 3 mL just beneath the pleura and 5 mL deeper in the intercostal muscular tissue for a total of 8 mL per ICS. Injections will be completed utilizing a 21-guage needle and two 20-mL syringes.
PROCEDUREArm 2 "LipoB-S": Liposomal Bupivacaine via Serratus Anterior Plane Block
The anesthetic mixture is prepared by combining 266 mg (20 mL) of Liposomal Bupivacaine (Exparel®) with 50 mg (20 mL) of 0.25% Bupivacaine Hydrochloride, creating a mixture of 40 mL. This mixture is administered via serratus anterior plane block. One injection is administered by an anesthesiologist in the serratus anterior fascial plane, immediately prior to incision while in the operating room. The total volume of 40 mL is administered using a single-shot technique with a short-bevel, 21-guage needle, ensuring a negative aspiration for blood upon entry, no paresthesia on injection, and incremental injection under ultrasound guidance.
PROCEDUREArm 3 "LipoB-C": Liposomal Bupivacaine Administered via Combination Block
Patients randomized to Arm 3 will receive both a multi-level intercostal nerve block (ICNB) and a serratus anterior plane block (SAPB), with each containing half the dose of Liposomal Bupivacaine (LipoB) as compared to when administered as a single block in Arm 1 and Arm 2. The mixtures are as follows: 133mg (10mL) LipoB mixed with 25mg (10mL) 0.25% Bupivacaine Hydrochloride and 20mL of saline administered as SAPB by anesthesiologist immediately prior to incision while in the operating room AND 133mg (10mL) LipoB mixed with 25mg (10mL) 0.25% Bupivacaine Hydrochloride and 20mL of saline administered as ICNB prior to closure in at least 5 intercostal spaces as determined by administering surgeon, while in the operating room.
Sponsors
University of Texas Southwestern Medical Center
The University of Texas at Dallas
Simmons Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
Patient and outcomes-assessors (floor or ICU nurses, research nurses, any person administering study questionnaires) will be blinded. Provider administering regional block (surgeon or anesthesiologist) will not be blinded but will not collect post-operative outcomes data.
Intervention model description
The 3 treatment arms are as follows for intra-operative injection of Liposomal Bupivacaine (LipoB) as a regional anesthetic block: * Arm 1: Entire dose (20mL) of LipoB and (20mL) Marcaine® injected locally via multi-level intercostal nerve block (ICNB) * Arm 2: Entire dose (20mL) of LipoB and (20mL) Marcaine® injected regionally as serratus anterior plane block (SAPB) * Arm 3: Half dose (10mL) of LipoB and (10mL) Marcaine® mixed with 20cc saline injected as ICNB, half dose (10mL) of LipoB and (10mL) Marcaine® mixed with 20cc saline injected as SAPB.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Plan to undergo planned (elective) minimally invasive isolated R-VATS procedure, to include pulmonary anatomic resections (anatomic lobectomy, segmentectomy, and wedge resection if performed robotically) * Age ≥ 18 years old * Ability to understand and capacity/willingness to sign a written informed consent form
Exclusion criteria
* Age \< 18 years old * Unwilling to sign informed consent form, mentally challenged/delayed, or lacking capacity/unable to consent to participation in the trial own their own behalf * Vulnerable populations * Incarcerated individuals * Pregnant individuals * Breastfeeding individuals * Individuals with potentially altered pharmacokinetics and metabolism of study drugs * Renal failure: creatinine ≥ 2, or glomerular filtration rate \< 45 mL/min * Hepatic failure: serum ammonia \> 33 mcg/dL and/or Child-Pugh \> A * Individuals suffering from chronic pain * Individuals taking pre-operative narcotics * Patients undergoing emergent surgery or urgent surgery for acute, traumatic injuries * Patients undergoing extra-pleural resections, chest wall resection, pleurectomies, pleurodesis, and decortications * Planned concurrent abdominal procedure: for example, but not limited to, an esophagectomy * Patients requiring subcostal transversus abdominis plane (TAP) block * Use of a rib spreader during thoracic procedure * Patients admitted to the intensive care unit (ICU) post-operatively while sedated and intubated * Patients with major post-operative complications * Wedge resection for pulmonary bleb * Unanticipated pleurectomy, even if partial * Surgeon injects superficial wounds with LipoB
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| NRS AUC 72 | Post-operative day 0 to post-operative day 3 (if still present in the hospital) | The investigators will obtain the NRS NRS AUC 72 (units: NRS·hours) (units 0-10) from time 0, entry into the recovery room, to 72 hours after entry into the recovery room. Pain will be assessed by the nursing staff, typically every 4 hours, and by research staff at least once on post-operative days 1-3. The times t0,t1,…,tk in hours within the range of 0 to 72 hours will correspond to NRS scores y0,y1,…,yk. Using the trapezoidal rule over the observed interval (assuming irregular and irregular timing), where: AUC=∑i((yi+yi+1)/2)(ti+1-ti), the maximum NRS·hours would be 10 x 72 hours + 720. If an individual patient measurement is taken off-schedule, the actual time stamps will be utilized. The trapezoidal rule naturally accommodates irregular spacing. If a patient is discharged early, or there is missing data, the AUC will be computed over the observed intervals and reported as time-standardized AUC = (AUC over observed time)/observed hours x 72. |
| Numeric Rating Scale (NRS) | Post-operative day 0 to post-operative day 3 (if still present in the hospital) | A pain numeric rating scale will be administered to all patients in the trial from post-operative day 0 to post-operative day 3 in the hospital. Study personnel will gather a NRS value once a day for post-operative day 1-3 and nursing staff will gather a NRS value multiple times a day, typically every 4 hours, per their protocol. Average and maximum values (Likert scale 0-10) will be recorded each day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Quality-of-Life (Measured by Quality of Recovery Scale) | Post-operative day 1 to post-operative day 3 (if still present in the hospital), as well as at clinic follow-up at 2-5 weeks and via telephone at 90, 180, and 365 days post-operatively | Investigators will measure post-operative side effects, functional status, and quality-of-life using the Quality of Recovery 15 scale (QR-15). The QR-15 scale measures pain as well as patient daily functioning, enjoyment, relationships, and overall well-being. The QR-15 has previously been validated among the minimally-invasive Thoracic Surgery population, with large-scale studies demonstrating significantly different medial QR-15 scores before to after surgery, with the QR-15 showing significant negative correlations with pain intensity and during coughing in the post-operative period. Further, the pain dimension of the QR-15 correlated to patient "emotional state, physical comfort, and physical independence" at 24, 48, and 72 hours post-operatively. QR-15 may assess nausea, appetite, constipation, and fatigue levels, as well as return to baseline function including return to oral intake, bowel function and ambulation. This scale is favored in clinical use by many anesthesiologists. |
| Pain Interference via PROMIS Pain Interference (PROMIS-PI) | Clinic follow-up at 2-5 weeks and via telephone at 90, 180, and 365 days post-operatively | The PROMIS Pain Interference item banks assess self-reported consequences of pain on relevant aspects of one's life. This includes the extent to which pain hinders engagement with social, cognitive, emotional, physical, and recreational activities. Pain Interference also incorporates items probing sleep and enjoyment in life, though the item bank only contains one sleep item. The pain interference short forms are universal rather than disease-specific. All assess pain interference over the past seven days. |
| Quality of Sleep via PROMIS Sleep Disturbance Short Form (SF) | Post-operative day 1, as well as at clinic follow-up at 2-5 weeks and via telephone at 90, 180, and 365 days post-operatively | The PROMIS Sleep Disturbance-SF questionnaire will be administered on post-operative day 1, as well as during clinic and telephone follow-up. This questionnaire assesses overall quality of sleep. |
| Opioid Usage | Post-operative day 0 up to 14 days post-operation | All opioid usage-including medication type, dosage, and time of administration- will be documented in the medical record. Opioid usage will be converted in a standard fashion to morphine milligram equivalents (MME) per day which will be recorded for all patients. Total cumulative opioid consumption will also be noted. This data will allow the research team to note time until first opioid use after surgery, time until cessation of opioid use after surgery, and whether a patient is utilizing opioids at time of discharge. |
| Cognitive Function via Neurologic Electrical Response | During surgery (intra-operative EEG) with follow-up assessments (minimal mental state exams) post-operatively up to 14 days post-operation. | Study subjects will undergo processed electroencephalogram (EEG) monitoring during the procedure. This requires an EEG sensor strip to be placed across the forehead. The use of processed EEG is standard-of-care for anesthesia monitoring during VATS or R-VATS procedures. EEG monitoring intra-operatively will assess neurologic electrical response to treatments (medications, regional nerve blocks, etc.) administered while in the operating room. The anesthesiology team will examine minimal mental state post-operatively per routine care. |
| Respiratory Function via Incentive Spirometry | Post-operative day 0 up to 14 days post-operation | An incentive spirometer is a handheld device provided to surgical patients to encourage deep, slow breathing, physiologically re-expanding alveoli that may have collapsed due to under-recruitment during and after surgery. Incentive spirometry maximum volume (mL) is recorded daily as the standard-of-care. Maximum incentive spirometry volume will be noted as a secondary outcome measure as the ability to take deep breaths is often directly correlated to thoracic and chest wall pain. |
| Adverse Events | Post-operative day 0 to clinic follow-up at 2-5 weeks post-operatively | All post-operative complications will be documented. All adverse reactions to medications will also be documented. The most common adverse reactions associated with liposomal Bupivacaine are like those of Bupivacaine: nausea, constipation, vomiting, and pyrexia. There have been reports of adverse neurologic reactions with the use of local anesthetics, and toxic blood concentrations depress cardiac conductivity and excitability. |
| Length of Stay | From date of hospital admission for surgical procedure until date of discharge from hospital, assessed up to 104 weeks. | Length of hospital stay (days) and length of intensive care unit (ICU) stay will be documented for all patients. |
| Cost-of-Care | Peri-operative, assessed up to 2 weeks. | Cost-of-care is an important secondary outcome of this study. The study drugs-Liposomal bupivacaine (Exparel®) and 0.25% bupivacaine hydrochloride (Marcaine®)-are standard of care medications which would be provided to all patients regardless of trial enrollment. The injection volumes of each medication also do not vary between treatment arms. Thus, no difference in cost is incurred for study drugs. Cost-of-care differences arise from equipment costs for ICNB, SAPB, and combination blocks, as well as from billable procedure costs, physician relative value units (RVUs), OR time, and hospital stay time. An activity-based and item-based fee analysis will be performed in combination with LOS and operative time differences between treatment arms to complete a cost analysis as part of this trial. |
Countries
United States
Contacts
CONTACTInderpal S Sarkaria, MD, MBA
PRINCIPAL_INVESTIGATORInderpal S Sarkaria, MD, MBA
University of Texas Southwestern Medical Center
Outcome results
None listed