Spinal Anesthesia For Enhanced Recovery After Liver Surgery

Vasopressor-free days to 30 days after surgery will be defined as the number of days alive and not on vasopressors before 30 days. If the patient is on vasopressors at day 30 or dies prior to day 30, vasopressor-free days will be 0.

Cumulative norepinephrine (NE)-equivalent time-weighted dose (mcg·kg-¹·min-¹ of anesthesia time) of vasopressors and/or inotropes (phenylephrine, norepinephrine, dopamine, and/or epinephrine).

Cumulative norepinephrine (NE)-equivalent time-weighted dose (mcg·kg-¹·min-¹ of vasopressor and/or inotrope infusion duration) of vasopressors and/or inotropes (phenylephrine, norepinephrine, dopamine, and/or epinephrine).

Intraoperative plus cumulative postoperative intravenous (IV) fluid volume administered, excluding non-albumin blood products, total (mL) = sum of volumes of IV crystalloid and IV colloid administered

Numerical Rating Scale (NRS) Summed Pain Intensity Difference of movement-evoked pain (SPID-MEP) (calculated as Area Under the Curve [AUC] using the trapezoidal rule) over 0 to 72 hours after surgery (AUC-SPID-MEP_0-72h)

Rescue analgesia (parenteral opioid) use is defined as receipt of supplemental (i.e., in addition to that defined by the intervention protocols) doses of fentanyl, morphine, and/or hydromorphone via the intravenous (IV) route, either via patient-controlled analgesia (PCA) or nurse/physician administration.

Cumulative fluid balance (CFB) is defined as the sum of current daily fluid balance (DFB) and the sum of DFB from all preceding days. DFB (mL) = (total daily fluid input - total daily fluid output). Daily fluid input includes: (1) resuscitation fluids (isotonic crystalloid [at a rate >1 L/6 h]; colloids [albumin, hydroxyethyl starch]); (2) blood products (packed red blood cells; frozen plasma; platelets; cryoprecipitate); (3) maintenance and replacement fluids (dextrose-containing crystalloid; isotonic crystalloid [at a rate ≤1 L/6 h]); (4) nutrition (enteral nutrition [i.e., tube feeds]; parenteral nutrition; oral fluid intake); and (5) fluid creep (volume due to concentrated electrolytes; volume used to keep venous access open; intermittent and continuous medication). Daily fluid output includes: (1) blood loss; (2) urine output; (3) dialysis ultrafiltrate (if applicable); (4) losses through drains; and (5) losses through enteric (e.g., nasogastric) tubes.

Percentage fluid overload (% FO) is defined as the ratio between cumulative fluid balance and the initial body weight, in percentage: % FO = [(total fluid in (L) - total fluid out (L)) / admission body weight (kg) × 100].

Volume-related weight gain at time t (VRWG_t) is defined as the percentage body weight gain at time t, calculated as the difference between the baseline body weight and body weight at time t divided by baseline body weight (t = 0): VRWG_t (%) = [(body weight [kg]_t - body weight [kg]_0) / body weight [kg]_0 × 100%].

Patient-reported quality of recovery (QoR), as assessed using the 15-item Quality of Recovery (QoR-15) scale, with the change from baseline in the total QoR-15 score (range 0-150) at 72 hours postoperatively defining the analysis endpoint. The QoR-15 is a 15-item patient-completed questionnaire including items measuring pain, physical comfort, psychological support, emotional state, and independence in activities of daily living over the preceding 24 hours. Items are rated on a 10-point scale, with higher subscale (item) and total scale values indicating a better outcome. The scale's validity (content, criterion, and construct), reliability (test-retest and internal consistency [inter-item and split-half coefficients]), responsiveness (minimal clinically important difference [MCID] = 8.0), acceptability, and feasibility properties have been well-established.

Defined as time to first out-of-bed mobilization (sitting out of bed, standing or walking).

Defined as the later of (1) time to solid diet tolerance (recovery of upper GI function), and (2) time to first flatus or bowel movement.

The Patient-Reported Outcomes Measurement Information System (PROMIS®) Short Form v1.0 - Sleep Disturbance (SD) 8a scale assesses self-reported perceptions of sleep quality, sleep depth, and restoration associated with sleep. The 8-item self-report version (Short Form [SF]) of the PROMIS® SD 8a scale included in this study queries sleep disturbance symptomatology based on the past 7 days, with each item rated on a 5-point Likert scale ranging from 1 (never) to 5 (almost always). All item scores are summed to calculate a total raw score where higher scores indicate more severe sleep disturbance symptomatology. Psychometric evaluations of the 8-item PROMIS® SF SD 8a in a wide range of patient populations have provided support for its high reliability (test-retest, internal consistency) and validity (convergent, divergent, face, construct). A smaller between-group increase from baseline (preoperative) to 7-day postoperative PROMIS® SF SD 8a T-scores indicates a better outcome.

The Overall Benefit of Analgesia Score (OBAS) is a patient-reported outcome measure of seven pain-related quality-of-life indicators: (1) pain intensity at rest (scored 0-4, 0 = minimal pain, to 4 = maximum imaginable pain); patient-reported distress with respect to five opioid-related adverse effects (each scored 0-4, 0 = not at all, to 4 = very much): (2) vomiting, (3) itching, (4) sweating, (5) freezing, and (6) dizziness; and (7) patient satisfaction with pain treatment (scored 0-4, 0 = not at all, to 4 = very much). To calculate the OBAS score, the scores for items 1-6 and 4 minus the score for item 7 are summed for a total scale score range of 0 to 28, with lower values indicating a better outcome.

Duration (days) of index hospitalization from date of index operation to date of hospital discharge (censored at the earliest of hospital discharge, in-hospital death, or 30 days postoperatively).

Severe respiratory depression is defined as respiratory rate (RR) < 8 and/or hypoxemia (Spo2 < 90%) related to excessive somnolence and/or alveolar hypoventilation.

Severe opioid-induced sedation, as defined by Pasero-McCaffery Opioid-induced Sedation Scale (POSS) score of 3 or 4. The POSS is graded on a 5-point scale (S = sleep, easy to arouse; 1 = awake and alert; 2 = slightly drowsy, easily aroused; 3 = frequently drowsy, arousable, drifts off to sleep during conversation; 4 = somnolent, minimal or no response to verbal or physical stimulation), with scores of S, 1, and 2 considered acceptable levels of sedation, and scores of 3 or 4 considered unacceptable levels of sedation.

Delirium will be evaluated via trained nursing assessments using the 3-min Confusion Assessment Method (3D-CAM). The diagnosis of delirium by 3D-CAM requires a positive response to (1) acute onset or fluctuating course; and (2) inattention; and either (3) disorganized thinking or (4) altered level of consciousness. To reduce the likelihood of fluctuations or temporal changes, all assessments were completed between 11:00 AM and 2:00 PM and for each participant, within a 2-hour time period.

Postoperative surgical complications are assessed using the Clavien-Dindo classification (none, I, II, III, IV, or V) and classified by system.

Postoperative non-surgical complications are assessed using the Postoperative Morbidity Survey (POMS) based on retrospective review of medical charts and patient telephone follow-up at 30 days.

Postoperative surgical and non-surgical complications are graded using the Comprehensive Complication Index (CCI), a continuous scale ranking the severity of any combination of postoperative complications from 0 to 100 in each patient.