NRS AUC 72

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.

Post-operative day 0 to post-operative day 3 (if still present in the hospital)

Numeric Rating Scale (NRS)

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.

Post-operative day 0 to post-operative day 3 (if still present in the hospital)

Quality-of-Life (Measured by Quality of Recovery Scale)

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.

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

Pain Interference via PROMIS Pain Interference (PROMIS-PI)

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.

Clinic follow-up at 2-5 weeks and via telephone at 90, 180, and 365 days post-operatively

Quality of Sleep via PROMIS Sleep Disturbance Short Form (SF)

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.

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

Opioid Usage

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.

Post-operative day 0 up to 14 days post-operation

Cognitive Function via Neurologic Electrical Response

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.

During surgery (intra-operative EEG) with follow-up assessments (minimal mental state exams) post-operatively up to 14 days post-operation.

Respiratory Function via Incentive Spirometry

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.

Post-operative day 0 up to 14 days post-operation

Adverse Events

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.

Post-operative day 0 to clinic follow-up at 2-5 weeks post-operatively

Length of Stay

Length of hospital stay (days) and length of intensive care unit (ICU) stay will be documented for all patients.

From date of hospital admission for surgical procedure until date of discharge from hospital, assessed up to 104 weeks.

Cost-of-Care

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.

Peri-operative, assessed up to 2 weeks.