Special Feature

Tidal Volume Limitation for All Intubated Mechanically Ventilated Patients: Less Is More

By Dean R Hess, PhD, RRT, Respiratory Care, Massachusetts General Hospital, Department of Anesthesiology, Harvard Medical School, is Associate Editor for Critical Care Alert.

Dr. Hess reports no financial relationship to this field of study.

The lung-protective effects of low tidal volumes, as demonstrated by the ARDSnet study, are well accepted in patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). In the original ARDSnet study, 861 patients were assigned to receive a tidal volume of 6 mL/kg predicted body weight (PBW) or a tidal volume of 12 mL/kg PBW.1 In the lower tidal volume group, tidal volume was reduced further to a minimum of 4 mL/kg PBW if the end-inspiratory plateau pressure was greater than 30 cm H2O. In cases of severe acidosis or ventilator dyssynchrony, the tidal volume was increased to a maximum of 8 mL/kg, provided plateau pressure was ≤ 30 cm H2O. The lower tidal volume strategy was associated with a 31% patient mortality, whereas the conventional tidal volume strategy was associated with 40% mortality (relative risk reduction of 22%).

The results of the ARDSnet trial, combined with other supporting data, have resulted in a reduction in tidal volumes in patients with ALI and ARDS. Some argue that tidal volume limitation is less important than maintaining plateau pressures < 30 cm H2O.2 However, results from a secondary analysis of the ARDSnet trial suggest that there is benefit for tidal volume reduction from 12 mL/kg to 6 mL/kg PBW even when plateau pressure is ≤ 30 cm H2O.3 What is more controversial is whether low tidal volumes should be used even in patients who do not have ALI or ARDS at the time of intubation.

It is interesting to note that a tidal volume of 6 mL/kg is typically referred to as a low tidal volume in mechanically ventilated patients. However, normal tidal volume is 6 mL/kg. So it might make more sense to refer to normal tidal volumes vs large tidal volumes. Normal lung volumes are predicted from sex and height, as follows:

Males: PBW = 50 + 2.3 x (inches of height - 60)

Females: PBW = 45.5 + 2.3 x (inches of height - 60)

Traditionally, tidal volume settings have been recommended without regard to sex or height, exposing women and shorter patients to potentially injurious tidal volumes.

Low-Tidal-Volume Ventilation in Patients without ALI or ARDS

Gajic et al conducted a retrospective study of patients who received invasive mechanical ventilation for > 48 hours between January and December of 2001 in 4 ICUs.4 Of 332 patients who did not have ALI at the time of intubation, 80 patients (24%) developed ALI within the first 5 days of mechanical ventilation. Women were ventilated with larger tidal volumes than men (mean, 11.4 mL/kg vs 10.4 mL/kg PBW; P < 0.001) and tended to develop ALI more often (29% vs 20%; P = 0.068). In a multivariate analysis, the main risk factors associated with development of ALI were the use of large tidal volumes (odds ratio [OR], 1.3 for each mL above 6 mL/kg PBW; P < 0.001), transfusion of blood products (OR, 3.0; P < 0.001), pH < 7.35 (OR, 2.0; P = 0.032), and a history of restrictive lung disease (OR, 3.6; P = 0.044).

In another study by Gajic and colleagues, patients were identified who required mechanical ventilation for 48 hours but did not have ARDS at the onset of mechanical ventilation.5 Of 3261 mechanically ventilated patients who did not have ARDS at the time of intubation, 205 (6.2%) developed ARDS 48 hours or more after the onset of mechanical ventilation. Multivariate logistic regression analysis found the development of ARDS was associated with the initial ventilator settings: high tidal volume (OR, 2.6 for > 700 mL), high peak airway pressure (OR, 1.6 for > 30 cm H2O), and high PEEP (OR, 1.7 for > 5 cm H2O).

Fernández-Pérez et al evaluated whether intraoperative mechanical ventilation with large tidal volumes was associated with increased risk of post-pneumonectomy respiratory failure.6 They studied patients undergoing elective pneumonectomy from January 1999 to January 2003. Of 170 pneumonectomy patients who met inclusion criteria, 30 (18%) developed postoperative respiratory failure. Patients who developed respiratory failure were ventilated with larger intraoperative tidal volumes than those who did not (median, 8.3 mL/kg vs 6.7 mL/kg PBW; P < 0.001). In a multivariate regression analysis, larger intraoperative tidal volume was associated with development of postoperative respiratory failure (OR, 1.56 for each mL/kg increase).

In a prospective multicenter observational study (in 4 European ICUs), Mascia et al investigated the role of ventilatory management as a predictor of ALI in brain-injured patients.7 The study enrolled 86 severely brain-injured patients (Glasgow Coma Scale score < 9). Of these, 18 patients (22%) developed ALI. Those who developed ALI were initially ventilated with significantly higher tidal volume (9.5 ± 1 mL/kg vs 10.4 ± 1.1 mL/kg PBW), respiratory rate, and minute ventilation, and more often required vasoactive drugs (P < 0.05). The use of high tidal volume (OR, 5.4) and relatively high respiratory rate (OR, 1.8) were independent predictors of acute lung injury (P < 0.01).

Jia et al conducted a retrospective analysis of patients who received mechanical ventilation for > 48 hours between 2001 and 2005.8 Of 789 patients who did not have ARDS at hospital admission, ARDS developed in 152 patients (19%). Multivariable logistic regression showed that peak pressure, high net fluid balance, plasma transfusion, sepsis, and tidal volume were significantly associated with the development of ARDS. The authors concluded that these findings suggest that ARDS may be a preventable complication in some cases.

Based on their review of the literature, Shultz et al recommend avoidance of high plateau pressures and high tidal volumes in patients who do not have ALI or ARDS at the onset of mechanical ventilation.9 They acknowledge that this recommendation is based on expert opinion and low-level evidence. In the absence of higher levels of evidence, this recommendation appears prudent. Many mechanically ventilated and critically ill patients are at risk of developing ALI. These patients may have lung injury, but do not meet the criteria for ALI or ARDS. One or more subsequent hits can result in the development of ALI. Inappropriately high tidal volume may initiate or exacerbate pulmonary inflammation, which may induce the primary hit or form a second or third hit.

Yilmaz et al evaluated the effect of low-tidal-volume ventilation and a restrictive transfusion policy on the development of acute lung injury in mechanically ventilated patients.10 A multidisciplinary team of intensivists and respiratory therapists designed a protocol to limit tidal volume to ≤ 10 mL/kg PBW in all patients receiving invasive ventilation, and a recommendation to use 6-8 mL/kg PBW for patients at any risk of ALI or ARDS. A chart with calculated values of PBW was attached to each ventilator and provided on-line. Comprehensive didactic and web-based teaching was provided to physicians, nurses, and respiratory therapists. An interdisciplinary team of intensivists, surgeons, nurses, and transfusion specialists designed an algorithm for evidence-based transfusion. The frequency of ALI/ARDS was calculated per number of patients ventilated > 48 hours. Data were collected prospectively from 3 adult ICUs from June 2005 to May 2006 and compared with a historical cohort of patients who were treated in the same ICUs before protocol introduction (January to December 2001).

Of 375 patients who met the inclusion and exclusion criteria, 212 were ventilated before and 163 after the interventions. There was a decrease in tidal volume (10.6 mL/kg to 7.7 mL/kg PBW; P < 0.001), in peak airway pressure (31 cm H2O to 25 cm H2O; P < 0.001), and in the percentage of transfused patients (63% to 38%; P < 0.001) after the intervention. The frequency of ALI decreased from 28% to 10% (P < 0.001). The duration of mechanical ventilation decreased from a median of 5 to 4 days (P = 0.03). When adjusted for baseline characteristics in a multivariate logistic regression analysis, protocol intervention was associated with a reduction in the frequency of new ALI (OR, 0.21). The results of this study suggest that many cases of ALI may be iatrogenic and preventable.

Chronically ventilated patients with spinal cord injury are commonly ventilated with very large tidal volumes. The motivation for this strategy seems to be for dyspnea relief and avoidance of atelectasis. However, this strategy has not been rigorously evaluated against a low tidal volume strategy. Although harm related to this approach has not been reported, it is prudent to lower the tidal volume when these patients are admitted to the hospital for an acute illness, as an acute illness may be a second hit (in addition to the larger tidal volume), which could increase the risk for ALI.

Is the Use of Low Tidal Volumes Harmful?

There are several potentially adverse effects of low-tidal-volume ventilation. Lower tidal volumes may increase the likelihood of atelectasis.11 However, atelectasis may be avoided by use of PEEP, which can decrease not only the risk of atelectasis, but also the risk for ventilator-associated pneumonia.12 There is also concern for increased ventilator dyssynchrony with tidal volume limitation. When lower tidal volumes are used, it is important to increase the respiratory rate to avoid respiratory acidosis, which increases respiratory drive. Manipulations of ventilator settings, such as inspiratory flow, can also improve patient-ventilator interactions.13 In some cases, additional sedation may be necessary. One might speculate that the pain and anxiety associated with invasive mechanical ventilation might stimulate the respiratory drive and the sensation of air hunger when tidal volume is limited. It is interesting to note that use of lower tidal volumes in the ARDSnet study was not associated with a greater sedative requirement.14,15


High-level evidence strongly supports tidal volume limitation in patients with ALI and ARDS. Although the strength of the evidence is lower for patients who do not have ALI, it seems prudent to limit tidal volume to < 10 mL/kg in all intubated and mechanically ventilated patients. Although no randomized controlled trials have addressed the issue, accumulating lower levels of evidence suggest that lower tidal volumes than those used in the past should be adopted in most patients requiring mechanical ventilation.


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