Marcelo Gama de Abreu, Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, TU Dresden
Postoperative respiratory failure, particularly after surgery under general anaesthesia, adds to the morbidity and mortality of surgical patients. Anaesthesiologists inconsistently use positive end-expiratory pressure (PEEP) and recruitment manoeuvers in the hope that this may improve oxygenation and protect against postoperative pulmonary complications (PPCs), especially in obese patients. While it is uncertain whether a strategy using higher levels of PEEP with recruitment manoeuvers truly prevents PPCs in these patients, the use of higher levels of PEEP with recruitment manoeuvers could compromise intra-operative haemodynamics. PROBESE was designed to address these issues.
The hypothesis of the study is that an intra–operative ventilation strategy using higher levels of PEEP and recruitment manoeuvers, compared to ventilation with lower levels of PEEP without recruitment manoeuvers, prevents PPCs in obese patients at an intermediate-to-high risk for PPC.
PROBESE is an international multicentre double-blinded randomized controlled trial. Currently, more than 1200 patients have been included, which makes PROBESE the largest randomized controlled trial on mechanical ventilation ever. Despite these impressive numbers, our goal is to achieve 2013 patients in total.
Main study parameters/endpoints
The primary endpoint is the proportion of patients with PPCs. Secondary endpoints include intra-operative complications, need for postoperative ventilatory support (invasive and/or non-invasive ventilation), unexpected ICU admission or ICU readmission, the number of hospital-free days on postoperative day 90, and 90-day survival/mortality.
Obese adult patients with body mass index (BMI) ≥ 35 kg/m2 at intermediate-to-high risk for PPCs scheduled for open or laparoscopic surgery under general anaesthesia lasting for at least 2 h.
Key exclusion criteria
- Previous lung surgery
- Persistent haemodynamic instability or intractable shock
- History of severe chronic obstructive pulmonary disease (COPD)
- Recent immunosuppressive medication
- Severe cardiac disease
- Invasive mechanical ventilation longer than 30 minutes within the last 30 days
- Prevalent acute respiratory distress syndrome expected to require prolonged postoperative mechanical ventilation
- Severe pulmonary arterial hypertension
- Intracranial injury or tumour
- Neuromuscular disease
- Need for intraoperative prone or lateral decubitus position
- Need for one-lung ventilation
- Cardiac or Neurosurgery
- Planned reintubation following surgery
The main intervention in PROBESE is setting one of two levels of PEEP during intraoperative mechanical ventilation with low tidal volumes, as described below:
THE HIGHER PEEP LEVEL
Mechanical ventilation with protective tidal volume of 7 ml/kg of predicted body weight (PBW) and the level of PEEP at 12 cmH2O with lung recruitment manoeuvers performed hourly
THE LOWER PEEP LEVEL
Mechanical ventilation with protective tidal volume of 7 ml/kg PBW and the level of PEEP at 4 cmH2O without lung recruitment manoeuvers.
Patients are followed-up on postoperative days 1, 2, 3, 4, 5, and at discharge from hospital, as well as telephone contact at day 90.
The result of this important clinical investigation will fill an information gap and likely change the daily clinical practice in anaesthesia of obese patients. Considering the growing burden of obesity and morbid obesity in the operating rooms all around the world, this trial might impact on post-operative outcomes and length of hospital stay.
Become a co-author!
The policy for collaborative co-authorship of PROBESE is unique and designed to give credit to the invaluable efforts of anaesthesiologists worldwide. Investigators are eligible for a co-authorship for every 12 randomized patients successfully treated according to the study protocol. Furthermore, you are allowed to run your own sub-study upon application to the PROBESE steering committee.
How do you get involved?
We are recruiting study centres worldwide that care for patients with severe to morbid obesity, and who undergo general anaesthesia for an at least 2-hour surgical intervention. If your daily anaesthetic routine includes such patients and you want be to be part of our team, please feel free to contact me. The trial will not be finished before end 2017, so that there is still time to be part of this endeavour.
Marcelo Gama de Abreu, MD, MSc, PhD, DESA, Chief-Investigator of PROBESE, on behalf of the Steering Committee and the PROVEnet