by Tao Shen, MBBS, and Edward A. Bittner, MD, PhD, MSEd
High tidal volume (TV) (10-15mL/kg) mechanical ventilation has been historically encouraged for anesthetized patients in the OR, especially for abdominal and thoracic procedures. This practice was based on a study published in the New England Journal of Medicine in 1963. It followed a series of 18 patients undergoing laparotomy and showed higher TV resulted in less atelectasis, less acidosis, and improved oxygenation compared to lower TV.1 However, over the last 2 decades, laboratory and clinical studies have linked higher TV, especially with higher inflation pressure, to a greater degree of lung injury. Indeed, the concept of lung protective ventilation was popularized by the landmark Acute Respiratory Distress Syndrome (ARDS)—net study published in 2000 showing lower TV (6-8 mL/kg) improves survival in ventilated critically ill patients with ARDS.2 This finding prompted a categorical change in ventilatory practice in critically ill patients with lung injury, and raised questions regarding the benefit of low TV ventilation for patients with uninjured lungs.
Over the past few years, a growing number of studies have related improved postoperative outcomes with intraoperative low TV ventilation.3 Despite this growing body of evidence, slow adoption of lung protection in the OR has occurred. Since choosing lower TV is easy to implement and incurs no additional cost, shouldn’t use of low TVs be considered the approach to ventilate patients during surgery? This article provides a brief overview of the physiological rationale and clinical evidence in support of low TV ventilation in the operating room in an effort to inform and provide practical guidance for clinicians.
Lung Protective Ventilation—Physiological Rationale
Mechanical ventilation can cause lung injury (known as ventilator-induced lung injury (VILI)) via a number of different mechanisms, including repeated over-distension of aerated lung (volutrauma), cyclic recruitment and de-recruitment of lung units (atelectrauma), and application of high plateau pressures (barotrauma).4 The deleterious effects of mechanical ventilation appear to be mediated by localized inflammation and the systemic release of inflammatory cytokines (biotrauma). Biotrauma not only promotes lung injury, but can also contribute to systemic injury due to the spillover of these inflammatory mediators into the systemic circulation, inducing remote organ dysfunction.5
General anesthesia affects lung function primarily by the loss of muscle tone, which promotes the development of lung atelectasis. The development of atelectasis is very common and occurs in more than 90 % of subjects undergoing general anesthesia, especially when accompanied by neuromuscular blockade.6 Lung atelectasis may also promote the development of VILI by overdistension of non-collapsed lung units and by the cyclical opening and closing of adjacent collapsible lung units.
Animal studies of VILI have frequently used a multiple-hit approach in which lung injury was first triggered by a preceding insult (e.g., systemic inflammation or sepsis) and then amplified by the harmful effects of large TV.7,8 However, studies have also demonstrated that ventilation with high TV alone—without a preceding insult—can also induce VILI.9 Of particular note, the majority of animal models of VILI have used relatively short periods of ventilation, resembling the clinical conditions of the operating room.
These findings suggest that ventilation strategies that use high tidal volumes during surgery may be harmful. Furthermore, it can be surmised that the potential harmful effects of mechanical ventilation may be minimized by the use of lower TVs that cause less lung distension, coupled with positive end-expiratory pressure (PEEP), or recruitment maneuvers to maintain lung volume.
Clinical Evidence for Lung Protective Ventilation
A number of small clinical studies of intraoperative ventilation suggested that low TV ventilation could improve pulmonary mechanics and oxygenation,10,11 reduce local production of inflammatory mediators,12 and shorten duration of postoperative ventilation.13 A pooled meta-analysis of 8 of these studies also suggested that low TV intraoperative ventilation strategies were associated with a reduced incidence of postoperative pulmonary complications.14 Three recent randomized controlled trials (RCTs) in patients undergoing a variety of surgeries have provided further evidence for the benefits (including improved postoperative pulmonary function and reduced pulmonary complications) of intraoperative ventilation with low TV (6-7 ml/kg predicted body weight (PBW)).15,16,17 It is important to emphasize that, in all 3 trials, lung-protective ventilation consisted of a bundle of measures: with differences in the size of TVs, levels of PEEP, and use of recruitment maneuvers; as such, it is not possible to ascertain which protective measure caused most benefit. However, a recent individual patient data meta-analysis, which included data from these 3 trials, suggested that benefit from lung-protection was best explained from TV reductions, and not from higher levels of PEEP.3
While it is important to acknowledge that using low TV without PEEP promotes atelectasis formation, the optimal PEEP for intraoperative lung protection remains unclear. One recently published multicenter RCT of low TV (8 ml/kg) in non-obese patients undergoing abdominal surgery compared intraoperative ventilation with low levels of PEEP (0 – 2 cm H2O) versus high levels of PEEP (12 cm H2O).18 There were no differences in the incidence of postoperative pulmonary complications between groups.18However, the use of higher PEEP levels was associated with intraoperative hypotension and a greater need for vasoactive drugs. Despite these findings other patient populations may benefit from higher levels of PEEP such as those who are obese or who are undergoing laparoscopic abdominal surgery with gas insufflation that may increase atelectasis. Still, the optimal combination of PEEP and TV, as well as the additional benefits of recruitment maneuvers is unknown.
Current Practice and Moving Forward
Low TV ventilation is increasingly being employed in the operation room, as suggested by a recent report on intraoperative ventilation practices in 5 large university hospitals in the US.19 In that study, almost 60% of cases used median tidal volumes < 8 mL per kg of PBW in 2013 compared with less than 25% of cases in 2005. While it is certainly possible that further expansion of the practice of intraoperative low TV ventilation could result in clinical benefit for some patients, it is important to consider whether there is any potential harm associated with widespread adoption of this practice. It has been argued that for some patients, ventilation with low tidal volumes can promote atelectasis, increase patient-ventilator dys-synchrony, and increase patient effort during spontaneous ventilation, which could cause fatigue and lung injury.20 Each of these detrimental effects could therefore offset the potential beneficial effects of low TV. Since a reduction in lung stress during mechanical ventilation is the mechanistic explanation for the beneficial effects of lower TVs, the selection of lung protective ventilation should likely be individualized. When employing low TV ventilation, clinicians should consider the type and duration of procedure, preexisting lung compliance, and the presence of pulmonary disease, as well as the consequences on lung stress if a patient is allowed to breathe spontaneously or will receive controlled ventilation.
Going forward, a number of questions regarding the specifics of intraoperative lung protective ventilation remain unanswered including the optimal levels of driving pressure, the benefits of lung recruitment maneuvers, and selection of optimal levels of PEEP. Fortunately, a number of randomized control trials are underway to better characterize methods of lung protection in specialized populations.21-23 The results of these trials have the potential to further improve the safety of intra-operative ventilation. Until that information is available, the existing evidence would suggest that controlled ventilation using low tidal volumes together with the use of low to moderate levels of PEEP is a safe practice and likely beneficial for the majority of patients during surgery.
- Bendixen HH, Hedley-Whyte J, Laver MB. Impaired oxygenation in surgical patients during general anesthesia with controlled ventilation. A concept of atelectasis.N Engl J Med 1963; 269:991–6.
- Acute Respiratory Distress Syndrome Clinical Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome.N Engl J Med 2000; 342:1301–8.
- Serpa Neto A, Hemmes SNT, Barbas CSV, et al. Protective Versus Conventional Ventilation for Surgery: a systematic review and individual patient data meta-analysis.Anesthesiology 2015;123:66–78.
- Slutsky AS, Ranieri VM. Ventilator-induced lung injury.N Engl J Med 2013, 369:2126–2136.
- Hegeman MA, Henmus MP, Heijnen CJ, et al. Ventilator-induced endothelial activation and inflammation in the lung and distal organs.Crit Care2009;13:R182.
- Duggan M, Kavanagh BP. Pulmonary atelectasis: a pathogenic perioperative entity.Anesthesiology 2005;102:838–854.
- Slutsky AS, Tremblay LN. Multiple system organ failure. Is mechanical ventilation a contributing factor?Am J Respir Crit Care Med 1998;157:1721–5.
- Tremblay L, Valenza F, Ribeiro SP, Li J, Slutsky Injurious ventilatory strategies increase cytokines and c-fos m-RNA expression in an isolated rat lung model.J Clin Invest 1997;99:944–52.
- Silva PL, Negrini D, Rocco PR. Mechanisms of ventilator-induced lung injury in healthy lungs.Best Pract Res Clin Anaesthesiol 2015;29:301–13.
- Chaney MA, Nikolov MP, Blakeman BP, Bakhos M. Protective Ventilation Attenuates Postoperative Pulmonary Dysfunction in Patients Undergoing Cardiopulmonary Bypass.J Cardiothorac Vasc Anesth 2000;14:514–8.
- Michelet P, D’Journo XB, Roch A, et al. Protective ventilation influences systemic inflammation after esophagectomy: a randomized controlled study.Anesthesiology2006;105:911–9.
- Zupancich E, Paparella D, Turani F, et al. Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial.J Thorac Cardiovasc Surg2005;130:378–83.
- Sundar S, Novack V, Jervis K, et al. Influence of low tidal volume ventilation on time to extubation in cardiac surgical patients.Anesthesiology 2011;114:1102–1110.
- Hemmes SN, Serpa Neto A, Schultz MJ. Intraoperative ventilatory strategies to prevent postoperative pulmonary complications: a meta-analysis.Curr Opin Anaesthesiol 2013;26:126–33.
- Severgnini P, Selmo G, Lanza C, et al. Protective mechanical ventilation during general anesthesia for open abdominal surgery improves postoperative pulmonary function.Anesthesiology 2013;118:1307–21.
- Futier E, Constantin JM, Paugam-Burtz C, et al. A trial of intraoperative low-tidal-volume ventilation in abdominal surgery.N Engl J Med 2013;369:428–37.
- Ge Y, Yuan L, Jiang X, Wang X, Xu R, Ma W. Effect of lung protection mechanical ventilation on respiratory function in the elderly undergoing spinal fusion.Zhong Nan Da Xue Xue Bao Yi Xue Ban 2013;38:81–5.
- PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology, Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial.Lancet 2014;384:495–503.
- Wanderer JP, Ehrenfeld JM, Epstein RH, et al. Temporal trends and current practice patterns for intraoperative ventilation at S. academic medical centers: a retrospective study.BMC Anesthesiol 2015;15:40.
- Gattinoni L.Counterpoint: Is low tidal volume mechanical ventilation preferred for all patients on ventilation? No.Chest 2011;140:11–3.
- Technische Universität Dresden. Protective Ventilation With Higher Versus Lower PEEP During General Anesthesia for Surgery in Obese Patients (PROBESE). Available from: http://clinicaltrials.gov/show/NCT02148692 Last Accessed 4/1/2016.
- Assistance Publique – Hôpitaux de Paris. Pulmonary Surgery and Protective Mechanical Ventilation (VPP). Available from: http://clinicaltrials.gov/show/NCT00805077 Last Accessed 4/1/2016.
- Fundación para la Investigación del Hospital Clínico de Valencia. Individualized Perioperative Open Lung Ventilatory Strategy (iPROVE). Available from http://clinicaltrials.gov/show/NCT02158923 Last Accessed 4/1/2016.
Tao Shen, MBBS, is a Clinical Fellow in Anaesthesia, Harvard Medical School.
Edward A. Bittner is Program Director of the Critical Care-Anesthesiology Fellowship and Associate Director of the Surgical Intensive Care Unit at Massachusetts General Hospital. He is Assistant Professor of Anaesthesia, Harvard Medical School, Massachusetts General Hospital.