Preoperative BOTOX® Injection for Large Ventral Hernia Repair

Primary fascial closure (PFC) is the successful closure of the hernia. It will be defined in a binary, categorical manner as: "Yes" (fascial closed) or "No" (fascia not closed and bridging mesh required). To be considered "Yes" for PFC, the midline anterior fascia must be completely re-approximated via absorbable running or figure-of-eight sutures. If any segment of the anterior fascia cannot be approximated and closed, the patient will require anterior bridging and this would be considered a failure of PFC.

Surgeons will decide if the fascia can be closed or if it cannot be closed by their expertise and discretion. No prespecified criteria have been established which dictate operative decision-making. The study team will record an outcome of "Yes" for PFC if the fascia is successfully closed by the surgeon via an eligible technique as previously described.

SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 30 days of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any incisional or organ/space infection within 30 days, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 30 days. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any inpatient hospital readmission within 30 days of index surgery. "How measured": EHR review/REDCap; unit = participants (%).

Any return to the operating room related to the index surgery within 30 days. "How measured": EHR/REDCap; unit = participants (%).

Days from operation to hospital discharge. "How measured": EHR discharge date minus surgery date; unit = days.

Any ICU care during the index stay or within 30 days (planned or unplanned). "How measured": EHR/REDCap; unit = participants (%).

Total ventilator time during and after surgery until final extubation during the index stay. Will be sub-divided as during surgery and after surgery. "How measured": anesthesia/intensive care record; unit = hours (may also be displayed as days:hours)

MI within 30 days per treating clinician diagnosis. "How measured": medical record review, patient interview, and/or clinical diagnosis. Unit = participants (%).

Clinically diagnosed pneumonia within 30 days. "How measured": patient interview, medical record review, or clinical diagnosis. Unit = participants (%).

Acute kidney injury/failure within 30 days. "How measured": clinician diagnosis, medical record review, and/or KDIGO Guidelines. Unit = participants (%).

Ileus requiring clinical management within 30 days. Defined as placement of an nasogastric tube or clinical diagnosis by surgeon based on intolerance of oral intake or delayed return of bowel function. "How measured": medical record review or clinician diagnosis. Unit = participants (%).

Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.

12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).

Highest complication grade based on the Clavien-Dindo classification system per participant within 30 days. "How measured": graded in REDCap from clinical documentation; unit = participants in each grade (%). Minimum = I, maximum = V; higher grades = worse.

SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 90 days of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any incisional or organ/space infection within 90 days, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 90 days. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).

Highest complication grade based on the Clavien-Dindo classification system per participant within 90 days. "How measured": graded in REDCap from clinical documentation; unit = participants in each grade (%). Minimum = I, maximum = V; higher grades = worse.

Comprehensive Complication Index® score, which is a weighted score based on the number of complications in each Clavien-Dindo group within 90 postoperative days. "How measured": the individuals CCI score at 90-days, as calculated via https://www.cci-calculator.com/.

Any inpatient hospital readmission within 30 days of index surgery. "How measured": EHR review/REDCap; unit = participants (%).

Any return to the operating room related to the index surgery within 90 days. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).

Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.

12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).

SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 1 year of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any incisional or organ/space infection within 1 year, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 1 year. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any return to the operating room related to the index surgery within 1 year. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).

Any return to the operating room related repair of a hernia within 7 cm of the hernia repaired in the original surgery within 1 year. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).

A recurrence after hernia repair is defined as a new hernia detected within 7cm of the original repair. The hernia must be determined via imaging (ultrasound, computed tomography scan, or magnetic resonance imaging scan) or the documented physical exam of a licensed practitioner. Determined as within 1 year of the hernia repair surgery.

Patient self-reported concern for recurrence based on response to the the question, "Do you feel or see a bulge?" on the Ventral Hernia Recurrence Inventory (VHRI) questionnaire. Asked at 1 year.

Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.

12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).

SSOs will be abstracted from the clinical record in a prospective fashion. They are defined as wound-related problems at or near the incision within 2 years of surgery (e.g., infection, fluid or blood collections, wound separation, or skin edge death). These will be measured on an individual level basis, and will be captured via patient interview and chart review within the specified timeframe. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any incisional or organ/space infection within 2 years, identified by treating teams. These will be measured on an individual level basis, and will be captured via patient interview, clinician-report, and/or chart review within the specified timeframe. Defined via any antibiotic and/or antimicrobial treatment of an infection at the surgical site. Positive culture or proof of pathogen not needed. Aggregate calculation for a population: numerator = participants with ≥1 SSO; denominator = all randomized participants who underwent surgery; unit = participants (%).

These are SSO events (as described in 30-Day SSO outcome) that required a bedside/clinic or OR procedure (e.g., aspiration, drainage, debridement) within 2 years. Cumulative SSOPIs will be calculated for each group. Additionally, aggregate calculation for a study group: numerator = participants with ≥1 SSOPI; denominator = all randomized participants who underwent surgery; unit = participants (%).

Any return to the operating room related to the index surgery within 2 years. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).

Any return to the operating room related repair of a hernia within 7 cm of the hernia repaired in the original surgery within 2 years. "How measured": patient interview, medical record review, surgeon report; unit = participants (%).

A recurrence after hernia repair is defined as a new hernia detected within 7cm of the original repair. The hernia must be determined via imaging (ultrasound, computed tomography scan, or magnetic resonance imaging scan) or the documented physical exam of a licensed practitioner. Determined as within 2 years of the hernia repair surgery.

Patient self-reported concern for recurrence based on response to the the question, "Do you feel or see a bulge?" on the Ventral Hernia Recurrence Inventory (VHRI) questionnaire. Asked at 2 years.

Three-item pain intensity questionnaire. "How measured": PROMIS-3a administered at follow-up; raw sum (3-15) converted to T-score (mean 50, SD 10); higher scores = more pain (worse). Unit = T-score.

12-item hernia-specific QoL instrument. "How measured": HerQLes administered at follow-up; score transformed 0-100, higher = better function/less disability. Unit = total score (0-100).

Force required to bring each fascial edge to midline, measured twice: (1) after initial dissection/before retro-rectus release and (2) after each step during posterior component separation. "How measured": sterile Kocher clamps attached to fascia will be connected to a sterilizable tensiometers which is pulled until midline is reached by medial fascial edge; force recorded. Unit = pounds of force (lbs); higher values = greater tension.

Ventilator plateau pressure measured (a) after intubation before incision, (b) just before skin closure (after repair), and (c) POD1 if still intubated. "How measured": volume-controlled ventilation; inspiratory pause 0.5-3 s; stabilized pressure recorded as Pplat; also record PIP, tidal volume, ventilator mode, PEEP, FiO₂. Unit = cmH₂O.

Difference between pre-closure and post-closure plateau pressures; negative change indicates improved mechanics. "How measured": subtraction of time-point values. Unit = cmH₂O.

Measured three times for all patients: (1) after anesthesia before incision and (2) immediately pre-extubation; also (3) on POD1 prior to Foley removal. "How measured": per WSACS consensus - instill ≤25 mL sterile saline via stopcock into a clamped Foley; patient supine with bed flat; transduce at mid-axillary line at end-expiration. Unit = mmHg.

Calculated as mean arterial pressure (MAP) - intra-abdominal pressure (from bladder pressure). "How measured": MAP (non-invasive or invasive, properly zeroed will be collected during regular care) and bladder pressure (as described above); APP computed. Unit = mmHg

Maximum width and length of the hernia defect following dissection/component separation. "How measured": intra-operative ruler measurement; unit = centimeters.

If PFC not achieved, the residual anterior defect dimensions at closure. "How measured": intra-op ruler; unit = cm.

If posterior sheath cannot be closed, record dimensions. "How measured": intra-op ruler; unit = cm. Note: posterior bridging does not equal PFC failure.

Surgeon-reported reason(s) categorized and tallied (e.g., excessive tension, loss of domain, patient instability). "How measured": operative note; unit = participants per category (%).

Participants still intubated at the end of the operation. "How measured": anesthesia record; unit = participants (%).

Direct transfer to ICU from OR/PACU after surgery. "How measured": disposition orders; unit = participants (%).

ICU transfer after initial non-ICU disposition. "How measured": bed movement logs/orders; unit = participants (%).

All-cause direct costs during the surgical global period (90 days). "How measured": institutional cost accounting; unit = USD.

Interval from image-guided injection to operative date. "How measured": scheduling records; unit = days. (Target window 21-48 days.)