2019-10-03 07:54:42 | BioPortfolio


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.

Study Design


Postoperative Pulmonary Complications


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


Not yet recruiting


Massachusetts General Hospital

Results (where available)

View Results


Published on BioPortfolio: 2019-10-03T07:54:42-0400

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Medical and Biotech [MESH] Definitions

The intentional interruption of transmission at the NEUROMUSCULAR JUNCTION by external agents, usually neuromuscular blocking agents. It is distinguished from NERVE BLOCK in which nerve conduction (NEURAL CONDUCTION) is interrupted rather than neuromuscular transmission. Neuromuscular blockade is commonly used to produce MUSCLE RELAXATION as an adjunct to anesthesia during surgery and other medical procedures. It is also often used as an experimental manipulation in basic research. It is not strictly speaking anesthesia but is grouped here with anesthetic techniques. The failure of neuromuscular transmission as a result of pathological processes is not included here.

The use of peripheral nerve stimulation to assess transmission at the NEUROMUSCULAR JUNCTION, especially in the response to anesthetics, such as the intensity of NEUROMUSCULAR BLOCKADE by NEUROMUSCULAR BLOCKING AGENTS.

Various salts of a quaternary ammonium oxime that reconstitute inactivated acetylcholinesterase, especially at the neuromuscular junction, and may cause neuromuscular blockade. They are used as antidotes to organophosphorus poisoning as chlorides, iodides, methanesulfonates (mesylates), or other salts.

Cetyltrimethylammonium compounds that have cationic detergent, antiseptic, and disinfectant activities. They are used in pharmaceuticals, foods, and cosmetics as preservatives; on skin, mucous membranes, etc., as antiseptics or cleansers, and also as emulsifiers. These compounds are toxic when used orally due to neuromuscular blockade.

Bactericidal cationic quaternary ammonium surfactant used as a topical anti-infective agent. It is an ingredient in medicaments, deodorants, mouthwashes, etc., and is used to disinfect apparatus, etc., in the food processing and pharmaceutical industries, in surgery, and also as a preservative. The compound is toxic orally as a result of neuromuscular blockade.


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