2012 Research Highlights
Mechanical ventilation: strategic improvements
www.thelancet.com/respiratory Vol 1 March 2013
for rescue sedation might restrict its acceptance by the intensive-care community as a first-line sedative drug. The present increasing tendency for continuous opioid infusion with intermittent benzodiazepine bolus dose, when required, might thus become the mainstay of mild-to-moderate sedation for ventilated patients. About 16% of patients in intensive care who are mechanically ventilated have acute lung injury. Until recently, classification of acute lung injury was defined by the American-European consensus conference as ARDS or acute lung injury non-ARDS.4 Although this consensus helped standardise management protocols and interpretation of research findings, some aspects of the definition were impractical. An often-quoted example is the requirement to definitively exclude left heart failure as the primary cause. In real world intensive care, ARDS can coexist with high pulmonary artery wedge pressures. The Berlin definition, published in 2012,5 is a practical approach to defining and categorising acute lung injury (now incorporated into ARDS). The strong points of the Berlin definition include a clear definition of acute (≤1 week between insult and onset of respiratory dysfunction) and objective assessment of cardiac function required only in the absence of any other cause of respiratory failure. Additionally, the subdivision of the previously broad category of ARDS into moderate and severe categories is practical in view of severity of illness
Published Online January 14, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70003-1
Gabrielle Voinot/Look at Sciences/Science Photo Library
Mechanical ventilation and its management have developed substantially in the past decade. Establishment of lung-protective ventilation by the acute respiratory distress syndrome (ARDS) network (ARDSNet) group,1 an improved understanding of cyclical alveolar opening, alveolar stress, and strain, and the role of positive end-expiratory pressure are only a few of the areas of advancement. However, sedation remains an inherent part of invasive mechanical ventilation to allow patients to tolerate endotracheal tubes, avoid device dislodgement, and for anxiolysis. For most patients managed with mechanical ventilation in the intensive-care environment, the best approach is use of the minimum dose of sedatives required to achieve tube tolerance and comfort (Richmond agitation sedation scale of 0 to –3). What is unclear is how to best achieve this dose. Early research suggested that daily interruption of sedation infusion was associated with reduced time to extubation and duration of intensive care and hospital stay. However, recent reports cast some doubt on these results. A recent study by Mehta and colleagues of 423 patients who were mechanically ventilated might help to clarify this issue.2 This study showed that time to extubation and duration of intensive care stay and hospital stay were not influenced by daily interruption of sedation infusion. Strikingly, daily sedation interruption was associated with a higher mean dose of sedative used than was uninterrupted sedation (102 mg per day vs 82 mg per day). The multicentre design, protocol-defined treatment of controls, and large number of patients add weight to the conclusions of the report. In Mehta’s report, benzodiazepines were used as the sedative drugs, with opioids co-administered for analgesia. In the quest for optimum sedation in patients who were mechanically ventilated, sedation protocols based on drugs other than benzodiazepines have also been assessed. For example, the α2 agonist dexmedetomidine was shown to be non-inferior to midazolam or propofol for mild-to-moderate sedation of patients who were mechanically ventilated.3 Dexmedetomidine was associated with shorter duration of mechanical ventilation and a reduced incidence of delirium and critical illness polyneuropathy. However, the incidence of hypotension, bradycardia, and need
e11
2012 Research Highlights
and prognostication. The main flaw of the Berlin definition and previous definitions is the absence of uncompensated hypercapnoea in both definitions. During the 2009 influenza A H1N1 pandemic, we noted a small but significant number of patients with severe hypoxaemia or uncompensated hypercapnoea who were thought to be refractory to optimum conventional mechanical ventilation. The presence of this group of patients focused our attention on alternatives and adjuncts to mechanical ventilation including prone positioning, interventional lung assist device, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation (ECMO). Although ECMO reduces mortality in severe ARDS secondary to H1N1 pneumonitis,6 no mortality risk scoring system existed in 2009. The ECMONet score has been developed by Pappalardo and colleagues on the basis of predictors of mortality identified in the Italian H1N1 ECMO network.7 These predictors included creatinine, bilirubin, haematocrit, hospital length of stay before the start of ECMO, and mean arterial pressure. Although useful for determination of ECMO prognosis in H1N1, the effect of the ECMONet score on decisions to offer or institute ECMO support remains to be established. We suspect that, for now, ECMO support will be offered to all patients who fulfil criteria (as outlined in the CESAR trial8) irrespective of the ECMONet score. Much has been said over the years about lung protective ventilation in ARDS. However, research into optimal tidal volumes, optimum positive end-expiratory pressure, and lung protection in mechanical ventilation in the absence of this syndrome has not had the same intensity of attention. We have intuitively evolved, probably from lessons learnt about barotrauma and volume trauma, to adopt less aggressive ventilator strategies in all patients who are mechanically ventilated. This strategy is supported by a recent meta-analysis9 that showed improved clinical outcomes associated with lung protective ventilation in the absence of ARDS.
e12
Questions remain about the best mechanical ventilation strategy and adjuncts or alternatives to mechanical ventilation. 2013 will hopefully provide some answers. Early results from the high-frequency oscillation in ARDS trial (OSCAR) and effect of prone positioning in patients with severe and persistent ARDS (PROSEVA) trial have been presented at professional meetings and the published articles are awaited with great anticipation. The extracorporeal membrane oxygenation for severe ARDS (EOLIA) trial will add to the ECMO debate. *Moronke A Noah, Giles J Peek Heartlink ECMO centre, University Hospitals of Leicester NHS trust, Leicester, UK [email protected] We declare that we have no conflicts of interest. 1
2
3
4
5 6
7
8
9
The Acute Respiratory Distress Syndrome 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: 1301–08. Mehta S, Burry L, Cook D, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012; 308: 1985–92. Jakob SM, Ruokonen E, Grounds R, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012; 307: 1151–60. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149: 818–24. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA 2012; 307: 2526–33. Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1). JAMA 2011; 306: 1659–68. Pappalardo F, Pieri M, Greco T, et al. Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: the ECMOnet score. Intensive Care Med 2012; published online Nov 16. DOI:10.1007/s00134-012-2747-1. Peek GJ, Mugford M, Tiruvoipati R, et al; CESAR Trial Collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374: 1351–63. Serpa Neto A, Cardoso S, Manetta J, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 2012; 308: 1651–59.
www.thelancet.com/respiratory Vol 1 March 2013
Mechanical ventilation: strategic improvements
www.thelancet.com/respiratory Vol 1 March 2013
for rescue sedation might restrict its acceptance by the intensive-care community as a first-line sedative drug. The present increasing tendency for continuous opioid infusion with intermittent benzodiazepine bolus dose, when required, might thus become the mainstay of mild-to-moderate sedation for ventilated patients. About 16% of patients in intensive care who are mechanically ventilated have acute lung injury. Until recently, classification of acute lung injury was defined by the American-European consensus conference as ARDS or acute lung injury non-ARDS.4 Although this consensus helped standardise management protocols and interpretation of research findings, some aspects of the definition were impractical. An often-quoted example is the requirement to definitively exclude left heart failure as the primary cause. In real world intensive care, ARDS can coexist with high pulmonary artery wedge pressures. The Berlin definition, published in 2012,5 is a practical approach to defining and categorising acute lung injury (now incorporated into ARDS). The strong points of the Berlin definition include a clear definition of acute (≤1 week between insult and onset of respiratory dysfunction) and objective assessment of cardiac function required only in the absence of any other cause of respiratory failure. Additionally, the subdivision of the previously broad category of ARDS into moderate and severe categories is practical in view of severity of illness
Published Online January 14, 2013 http://dx.doi.org/10.1016/ S2213-2600(13)70003-1
Gabrielle Voinot/Look at Sciences/Science Photo Library
Mechanical ventilation and its management have developed substantially in the past decade. Establishment of lung-protective ventilation by the acute respiratory distress syndrome (ARDS) network (ARDSNet) group,1 an improved understanding of cyclical alveolar opening, alveolar stress, and strain, and the role of positive end-expiratory pressure are only a few of the areas of advancement. However, sedation remains an inherent part of invasive mechanical ventilation to allow patients to tolerate endotracheal tubes, avoid device dislodgement, and for anxiolysis. For most patients managed with mechanical ventilation in the intensive-care environment, the best approach is use of the minimum dose of sedatives required to achieve tube tolerance and comfort (Richmond agitation sedation scale of 0 to –3). What is unclear is how to best achieve this dose. Early research suggested that daily interruption of sedation infusion was associated with reduced time to extubation and duration of intensive care and hospital stay. However, recent reports cast some doubt on these results. A recent study by Mehta and colleagues of 423 patients who were mechanically ventilated might help to clarify this issue.2 This study showed that time to extubation and duration of intensive care stay and hospital stay were not influenced by daily interruption of sedation infusion. Strikingly, daily sedation interruption was associated with a higher mean dose of sedative used than was uninterrupted sedation (102 mg per day vs 82 mg per day). The multicentre design, protocol-defined treatment of controls, and large number of patients add weight to the conclusions of the report. In Mehta’s report, benzodiazepines were used as the sedative drugs, with opioids co-administered for analgesia. In the quest for optimum sedation in patients who were mechanically ventilated, sedation protocols based on drugs other than benzodiazepines have also been assessed. For example, the α2 agonist dexmedetomidine was shown to be non-inferior to midazolam or propofol for mild-to-moderate sedation of patients who were mechanically ventilated.3 Dexmedetomidine was associated with shorter duration of mechanical ventilation and a reduced incidence of delirium and critical illness polyneuropathy. However, the incidence of hypotension, bradycardia, and need
e11
2012 Research Highlights
and prognostication. The main flaw of the Berlin definition and previous definitions is the absence of uncompensated hypercapnoea in both definitions. During the 2009 influenza A H1N1 pandemic, we noted a small but significant number of patients with severe hypoxaemia or uncompensated hypercapnoea who were thought to be refractory to optimum conventional mechanical ventilation. The presence of this group of patients focused our attention on alternatives and adjuncts to mechanical ventilation including prone positioning, interventional lung assist device, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation (ECMO). Although ECMO reduces mortality in severe ARDS secondary to H1N1 pneumonitis,6 no mortality risk scoring system existed in 2009. The ECMONet score has been developed by Pappalardo and colleagues on the basis of predictors of mortality identified in the Italian H1N1 ECMO network.7 These predictors included creatinine, bilirubin, haematocrit, hospital length of stay before the start of ECMO, and mean arterial pressure. Although useful for determination of ECMO prognosis in H1N1, the effect of the ECMONet score on decisions to offer or institute ECMO support remains to be established. We suspect that, for now, ECMO support will be offered to all patients who fulfil criteria (as outlined in the CESAR trial8) irrespective of the ECMONet score. Much has been said over the years about lung protective ventilation in ARDS. However, research into optimal tidal volumes, optimum positive end-expiratory pressure, and lung protection in mechanical ventilation in the absence of this syndrome has not had the same intensity of attention. We have intuitively evolved, probably from lessons learnt about barotrauma and volume trauma, to adopt less aggressive ventilator strategies in all patients who are mechanically ventilated. This strategy is supported by a recent meta-analysis9 that showed improved clinical outcomes associated with lung protective ventilation in the absence of ARDS.
e12
Questions remain about the best mechanical ventilation strategy and adjuncts or alternatives to mechanical ventilation. 2013 will hopefully provide some answers. Early results from the high-frequency oscillation in ARDS trial (OSCAR) and effect of prone positioning in patients with severe and persistent ARDS (PROSEVA) trial have been presented at professional meetings and the published articles are awaited with great anticipation. The extracorporeal membrane oxygenation for severe ARDS (EOLIA) trial will add to the ECMO debate. *Moronke A Noah, Giles J Peek Heartlink ECMO centre, University Hospitals of Leicester NHS trust, Leicester, UK [email protected] We declare that we have no conflicts of interest. 1
2
3
4
5 6
7
8
9
The Acute Respiratory Distress Syndrome 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: 1301–08. Mehta S, Burry L, Cook D, et al. Daily sedation interruption in mechanically ventilated critically ill patients cared for with a sedation protocol: a randomized controlled trial. JAMA 2012; 308: 1985–92. Jakob SM, Ruokonen E, Grounds R, et al. Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. JAMA 2012; 307: 1151–60. Bernard GR, Artigas A, Brigham KL, et al. The American-European Consensus Conference on ARDS: definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med 1994; 149: 818–24. ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin definition. JAMA 2012; 307: 2526–33. Noah MA, Peek GJ, Finney SJ, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1). JAMA 2011; 306: 1659–68. Pappalardo F, Pieri M, Greco T, et al. Predicting mortality risk in patients undergoing venovenous ECMO for ARDS due to influenza A (H1N1) pneumonia: the ECMOnet score. Intensive Care Med 2012; published online Nov 16. DOI:10.1007/s00134-012-2747-1. Peek GJ, Mugford M, Tiruvoipati R, et al; CESAR Trial Collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374: 1351–63. Serpa Neto A, Cardoso S, Manetta J, et al. Association between use of lung-protective ventilation with lower tidal volumes and clinical outcomes among patients without acute respiratory distress syndrome: a meta-analysis. JAMA 2012; 308: 1651–59.
www.thelancet.com/respiratory Vol 1 March 2013
