Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
estimated completion

Description

Summary

Postoperative pulmonary complications (PPCs) are a major cause of morbidity and mortality in surgical patients. National estimates suggest 1,062,000 PPCs per year, with 46,200 deaths, and 4.8 million additional days of hospitalization. Abdominal surgery is the field with the largest absolute number of PPCs. Our long-term goal is to develop and implement perioperative strategies to eliminate PPCs. Whereas PPCs are as significant and lethal as cardiac complications, research in the field has received much less attention, and strategies to minimize PPCs are regrettably limited. Recently, we and others have suggested a crucial role of anesthesia related interventions such as ventilatory strategies, and administration and reversal of neuromuscular blocking agents in reducing PPCs. These findings are consistent with the beneficial effects of lung protective ventilation during the adult respiratory distress syndrome (ARDS). While surgical patients differ substantially from ARDS patients as most have no or limited lung injury at the start of surgery, intraoperative anesthetic and abdominal surgery interventions result in lung derecruitment and predispose to or produce direct and indirect, potentially multiple-hit, lung injury. Thus, effective anesthetic strategies aiming at early lung protection in this group of patients are greatly needed. Indeed, the current lack of evidence results in wide and unexplained variability in anesthetic practices creating a major public health issue as some practices within usual care appear to be suboptimal and even potentially injurious. We hypothesize that an anesthesia-centered bundle, based on our recent findings and focused on perioperative lung protection, will minimize multiple and synergistic factors responsible for the multiple-hit perioperative pulmonary dysfunction and result in decreased incidence and severity of PPCs. Founded on strong preliminary data, we will leverage a network of US academic centers to study this hypothesis in two aims: Aim 1. To compare the number and severity of PPCs in patients receiving an individualized perioperative anesthesia-centered bundle to those in patients receiving usual anesthetic care during open abdominal surgery. For this, we propose to conduct a prospective multicenter randomized controlled pragmatic trial with a blinded assessor in a total of 750 patients. The bundle will consist of optimal mechanical ventilation comprising individualized positive end-expiratory pressure to maximize respiratory system compliance and minimize driving pressures, individualized use of neuromuscular blocking agents and their reversal, and postoperative lung expansion and early mobilization; Aim 2. To assess the effect of the proposed bundle on plasma levels of lung injury biomarkers. We theorize that our intervention will minimize overinflation and atelectasis reducing plasma levels of biomarkers of lung inflammatory, epithelial, and endothelial injury. Such mechanistic insights will facilitate bundle dissemination and support adoption as it has for lung protective ventilation for ARDS. At the end of this project, we expect to change clinical practice by establishing a new and clinically feasible anesthesia-centered strategy to reduce perioperative lung morbidity.

Keywords

Postoperative Pulmonary Complications Preoperative Education Intraoperative PEEP Individualization Individualization of Neuromuscular Blockade Postoperative Incentive Spirometry Postoperative Ambulation

Eligibility

You can join if…

Open to people ages 18 years and up

  • Adults (>=18 years) scheduled for elective surgery with expected duration >=2 hours
  • Open abdominal surgery including: gastric, biliary, pancreatic, hepatic, major bowel, ovarian, renal tract, bladder, prostatic, radical hysterectomy, and pelvic exenteration
  • Intermediate or high risk of PPCs defined by an ARISCAT risk score>=26

You CAN'T join if...

  • Inability or refusal to provide consent
  • Inability or significant difficulty to perform any study interventions, including incentive spirometry, ambulation and/or maintaining follow-up contact with study personnel for up to 90 days after the date of surgery.
  • Participation in any interventional research study within 30 days of the time of the study.
  • Previous surgery within 30 days prior to this study.
  • Pregnancy
  • Emergency surgery
  • Severe obesity (above Class I, BMI>=35 kg/m2)
  • Significant lung disease: any diagnosed or treated respiratory condition that (a) requires home oxygen therapy or non-invasive ventilation (except nocturnal treatment of sleep apnea without supplemental oxygen), (b) severely limits exercise tolerance to <4 METs (e.g., patients unable to do light housework, walk flat at 4 miles/h or climb one flight of stairs), (c) required previous lung surgery, or (d) includes presence of severe pulmonary emphysema or bullae
  • Significant heart disease: cardiac conditions that limit exercise tolerance to <4 METs
  • Renal failure: peritoneal or hemodialysis requirement or preoperative creatinine >=2 mg/dL
  • Neuromuscular disease that impairs ability to ventilate without assistance
  • Severe chronic liver disease (Child-Turcotte-Pugh Score >9, Appendix I)
  • Sepsis
  • Malignancy or other irreversible condition for which 6-month mortality is estimated >=20%
  • Bone marrow transplant

Locations

  • University of California - San Francisco accepting new patients
    San Francisco California 94115 United States
  • Stanford University accepting new patients
    Stanford California 94305 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Massachusetts General Hospital
ID
NCT04108130
Study Type
Interventional
Last Updated