EDUCATIONAL MATERIAL

Transcription

1 ERS Annual Congress Amsterdam September 2015 EDUCATIONAL MATERIAL Meet the expert 3 Mechanical ventilation: a friend and a foe Thank you for viewing this document. We would like to remind you that this material is the property of the author. It is provided to you by the ERS for your personal use only, as submitted by the author by the author Sunday, 27 September :00 14:00 Room G110 RAI

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3 NONINVASIVE VENTILATION... how to do it, why to do it, when to do it and when to stop! ERS Practical Handbook of Noninvasive Ventilation Edited by Anita K. Simonds ISBN (print) ISBN (ebook) (ERS members) 40 (non-members) The ERS Practical Handbook of Noninvasive Ventilation provides a concise why and how to guide to NIV from the basics of equipment and patient selection to discharge planning and community care. Editor Anita K. Simonds has brought together leading clinicians and researchers in the field to provide an easy-to-read guide to all aspects of NIV. Topics covered include: equipment, patient selection, paediatric indications, airway clearance and physiotherapy, acute NIV monitoring, NIV in the ICU, long-term NIV, indications for tracheostomy ventilation, symptom palliation, discharge planning and community care, and setting up an NIV service. This Practical Handbook is a valuable reference and training resource for all NIV practitioners. User-friendly format with key point summaries Focused on practical aspects and problem solving Multiple choice questions to enable self-assessment To buy printed copies, visit the ERS Bookshop at the ERS International Congress 2015 (Hall 1, Stand 1.D_12). Electronic: Print:

4 Mechanical ventilation: friend or foe Prof. Dr Theodoros Vassilakopoulos Department of Critical Care & Pulmonary Services University of Athens Medical School Athens GREECE AIMS: To understand the benefits and complications of mechanical ventilation TARGET AUDIENCE: Critical care physicians, respiratory care physicians, pulmonologists, respiratory therapists, physiotherapists, critical care nurses, scientists SUMMARY Mechanical ventilation can put the respiratory muscles at rest while providing adequate gas exchange. Despite the clear benefits of this therapy, many patients eventually die after the initiation of mechanical ventilation, even though their arterial blood gases may have normalized. This mortality has been attributed to many factors, including complications of ventilation such as barotrauma (i.e., gross air leaks), oxygen toxicity, and hemodynamic compromise. More recently, studies have been conducted on the worsening injury that mechanical ventilation can cause in previously damaged lungs and the damage it can initiate in normal lungs. This damage is characterized pathologically by inflammatory-cell infiltrates, hyaline membranes, increased vascular permeability, and pulmonary edema. Thia type of injury has been termed ventilator-induced lung injury (VILI). The clinical importance of ventilator-induced lung injury in adults was confirmed by a study showing that a ventilator strategy designed to minimize such injury decreased mortality among patients with the acute respiratory distress syndrome (ARDSnet study). Regional lung overdistention is a key factor in generating ventilator-induced lung injury. Since there is no well-accepted clinical method of measuring regional overdistention, limiting inflation pressure during mechanical ventilation is used as a surrogate strategy to limit overdistention. Ventilator-induced lung injury can occur because of ventilation at high (absolute) lung volumes, leading to alveolar rupture, air leaks, and gross barotrauma (e.g., pneumothorax, pneumomediastinum, and subcutaneous emphysema. The term barotrauma can be misleading, because the critical variable leading to the air leaks is regional lung overdistention, not high airway pressure per se. More subtle injury that is manifested as pulmonary edema can occur as a result of lung overdistention Ventilation that occurs at low (absolute) lung volumes can also cause injury through multiple mechanisms, including repetitive opening and closing of airways and lung units, effects on surfactant function, and regional hypoxia. This type of injury, which is characterized by epithelial sloughing, hyaline membranes, and pulmonary edema, has been termed atelectrauma. Atelectrauma is amplified in lungs in which there are marked heterogeneities in ventilation. During VILI various intracellular mediators are released. Some mediators may directly injure the lung; others may set the stage for subsequent development of pulmonary fibrosis. Additional mediators may act as homing molecules recruiting cells (e.g., neutrophils) to the lung, and such cells can then release more injurious molecules. This process has been termed biotrauma. 4

5 The translocation of mediators, bacteria, or lipopolysaccharide from the airspaces into the systemic circulation may occur in lungs that have increased alveolar capillary permeability, which is inherent in the case of ARDS or which is induced by volutrauma or epithelial microtears. This translocation may lead to subsequent multiorgan dysfunction and death. The recognition of the importance of ventilator-induced lung injury has changed our approach to mechanical ventilation. Whereas previously the goals of mechanical ventilation were to maintain gas exchange while minimizing the work of breathing, an additional goal has been established: to provide gas exchange that sustains life while minimizing ventilator-induced lung injury. Various ventilation strategies have been used to minimize lung injury: low tidal volumes to limit overdistention, higher PEEPs to prevent injury from low lung volume (atelectrauma), Patients with ARDS often have relatively nonaerated dependent lung regions (i.e., regions that are lower from a gravitational perspective than other regions and hence are more likely to be collapsed) and relatively normally aerated nondependent lung regions. Because there is a smaller volume available for ventilation, this condition has led to the term baby lung. The implication is that a decreased tidal volume (i.e., one that might be normal for a baby) should be used to prevent overinflation of the relatively small, normally aerated regions. In a seminal study that built on previous studies, the ARDS Network investigators compared a control strategy that used a tidal volume of 12 ml per kilogram of predicted body weight with a low-tidal-volume strategy that used 6 ml per kilogram of predicted body weight. The low-tidal-volume strategy was associated with an absolute reduction of 9 percentage points in the rate of death (39.8% vs. 31.0%). Pulmonary edema and end-expiratory alveolar collapse characterize several forms of respiratory failure. In these situations, a low PEEP may be insufficient to stabilize alveoli and keep them open, thereby increasing the likelihood of ventilator-induced lung injury from atelectrauma. Conversely, a higher PEEP has potentially adverse effects, including impairment of venous return and pulmonary overdistention. A recent meta-analysis of patient-level data in randomized trials addressed these tradeoffs in patients with ARDS and concluded that a higher PEEP was associated with an absolute reduction of 5 percentage points in the rate of death among patients who had worse oxygenation, defined as a ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO 2:FiO 2) of 200 mm Hg or less. Given the importance of transpulmonary pressure in lung injury, an obvious approach would be to use transpulmonary pressure to set the PEEP, with the use of esophageal pressure as a surrogate for pleural pressure. However, the interpretation of absolute esophageal pressure is difficult because of cardiac artifacts, the uneven distribution of pleural pressure (i.e., no single value of pleural pressure describes the entire lung), and esophageal distortion and contraction (especially in supine patients). This approach has been studied in a small series of patients with ARDS with promising results. About 70% of patients with ARDS and hypoxemia have improved oxygenation when they are placed in a prone position. Possible mechanisms for this effect include increased end-expiratory lung volume, better ventilation perfusion matching, less effect of the mass of the heart on the lower lobes, and improved regional ventilation. Most important, the prone position should minimize lung injury by increasing homogeneity of ventilation. A recent meta-analysis of seven trials involving a total of 1724 patients showed that prone positioning lowered absolute mortality by approximately 10 percentage points in the subgroup of patients with ARDS and severe hypoxemia (PaO 2:FiO 2 ratio, <100 mm Hg). In a recently completed trial involving 466 patients with ARDS who had a PaO 2:FiO 2 ratio of less than 150 mm Hg while receiving an Fio 2 of 0.60 or more, the rate of death at 28 days was 32.8% among those who were treated in the supine position and 16.0% among those treated in the prone position. 5

6 Because of extreme dyspnea, patients with ARDS often fight the ventilator, which may aggravate ventilator-induced lung injury. One therapeutic approach is to administer a neuromuscular blocking agent to ensure patient ventilator synchrony and facilitate limitations on tidal volume and pressure. In a recent multicenter, placebo-controlled, randomized trial involving 340 patients with ARDS and a PaO 2:FiO 2 ratio of less than 150 mm Hg, it was found that the adjusted 90-day mortality was lower among those who received a neuromuscular blocking agent for 48 hours than among those who received placebo, without any increase in residual muscle weakness. Ventilator Induced diaphragmatic dysfunction (VIDD) Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation. However, the use of controlled mechanical ventilation in animal models results in a major reduction of diaphragmatic forcegenerating capacity together with structural injury and atrophy of diaphragm muscle fibers, a condition termed ventilator-induced diaphragmatic dysfunction (VIDD). Increased oxidative stress and exaggerated proteolysis in the diaphragm have been linked to the development of VIDD in animal models, but much less is known about the extent to which these phenomena occur in humans undergoing mechanical ventilation in the ICU. Recently published data show that critically ill patients, exhibit a remarkable degree of similarity with the animal model data. Hence, the human studies to date have indicated that mechanical ventilation is associated with increased oxidative stress, atrophy, and injury of diaphragmatic muscle fibers along with a rapid loss of diaphragmatic force production. These changes are, to a large extent, directly proportional to the duration of mechanical ventilation. Noninvasive Mechanical ventilation According to several randomized controlled trials, NIV has gained acceptance as the preferred ventilatory modality to treat acute respiratory failure (ARF) due to chronic obstructive pulmonary disease exacerbations, cardiogenic pulmonary edema, respiratory failure in immunocompromised patients, and to decrease the intubation length and to improve weaning results in patients recovering from a hypercapnic respiratory failure. Observational studies suggest that NIV may also be used to treat other conditions like severe pneumonia, severe asthma attack, cystic fibrosis, obesity hypoventilation, and to improve the respiratory outcome in postsurgical patients. NIV has radically changed the management of ARF. Recently the possible applications of NIV have increased, both in the hospital and extrahospital setting. NIV is no longer confined to the ICU, but has crossed over into the regular ward, Emergency Department and 'out-of-hospital' environment. Patients with chronic airflow obstruction and difficult or prolonged weaning are at increased risk for prolonged invasive mechanical ventilation (IMV). Several randomized controlled trials mainly conducted in patients who had pre-existing lung disease have shown that the use of noninvasive ventilation (NIV) to advance extubation in patients with difficult and prolonged weaning can result in reduced periods of endotracheal intubation, complication rates, and improved survival. Patients in these studies were hemodynamically stable, with a normal level of consciousness, no fever, and a preserved cough reflex. The use of NIV in the management of mixed populations with respiratory failure after extubation, including small proportions of chronic respiratory patients did not show clinical benefits. By contrast, NIV immediately after extubation is effective in avoiding respiratory failure after extubation and improving survival in patients at risk for this complication, particularly those with chronic respiratory disorders, cardiac comorbidity, and hypercapnic respiratory failure. REFERENCES 1. Slutsky, A. S. and V. M. Ranieri Ventilator-induced lung injury. N.Engl.J.Med. 369: Vassilakopoulos, T Ventilator-induced diaphragm dysfunction: the clinical relevance of animal models. Intensive Care Med. 34:

7 3. Jaber, S., B. Jung, S. Matecki, and B. J. Petrof Clinical review: ventilator-induced diaphragmatic dysfunction--human studies confirm animal model findings! Crit Care 15: Boldrini, R., L. Fasano, and S. Nava Noninvasive mechanical ventilation. Curr.Opin.Crit Care 18: Ferrer, M., J. Sellares, and A. Torres Noninvasive ventilation in withdrawal from mechanical ventilation. Semin.Respir.Crit Care Med. 35: EVALUATION 1. What is the ideal tidal volume we should deliver in ARDS patients? a. 4 ml/kgr body weight b. 5 ml/kgr body weight c. 6 ml/kgr body weight d. 7 ml/kgr body weight e. 8 ml/kgr body weight f. None of the above 2. Which of the following modes is associated with the development of ventilator induced diaphragmatic dysfunction? a. Assist Control Ventilation b. Pressure Support Ventilation c. Controlled Mechanical Ventilation d. Synchronized Intermittent Mandatory Ventilation e. None of the above 3. How many days should we keep an ARDS patient on neuromuscular blockers? a. 1 day b. 2 days c. 3 days d. 4 days e. None of the above 4. In patients with COPD exacerbation noninvasive mechanical ventilation: a. Reduces intubation rate b. Increases intubation rate c. Reduces mortality d. Increases hospital stay e. a+c f. b+d 5. Which of the following is true regarding application of noninvasive ventilation (NIV) during extubation? a. NIV application reduces mortality in patients who fail extubation b. NIV application postpones the development of respiratory failure in patients who develop hypercapnia during a spontaneous breathing trial c. NIV application reduces reintubation rate in patients who fail extubation d. NIV application reduces mortality in patients who fail a spontaneous breathing trial e. None of the above 7

8 Mechanical ventilation: friend or foe Theodoros Vassilakopoulos MD, PhD Professor Department of Critical Care & Pulmonary Services, University of Athens Medical School Athens, Greece 8

9 I have no real or perceived conflicts of interest that relate to this presentation: This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgments. It remains for audience members to determine whether the speaker s interests, or relationships may influence the presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias or decreasing the value of the speaker s presentation. Drug or device advertisement is forbidden. 9

10 ARDS 10

11 11

12 Clinical Disorders associated with the development of ARDS Direct Lung Injury Common Causes Pneumonia Aspiration of gastric contents Less common causes Pulmonary contusion Fat emboli Near-drowning Inhalational injury Indirect Lung Injury Common Causes Sepsis Severe trauma (shock / multiple transfusions) Less common causes Cardiopulmonary bypass Drug overdose Acute pancreatitis Transfusions of blood products 12

13 PV curve in ARDS 13

14 Lung Injury Caused by Forces Generated by Ventilation at Low and High Lung Volumes. Slutsky AS, Ranieri VM. N Engl J Med 2013;369:

15 Ventilator Induced Lung Injury (VILI) Over-distention Repetitive opening and closing atelectasis 15

16 16

17 17

18 What is the tidal volume we should use for patients with ARDS? 18

19 Amato et al N Engl J Med 1998;338: ARDS (n = 53) RANDOMIZATION Protective Ventilation (n = 29) Traditional Ventilation (n = 24) Survival 28 d. 11/29 (38%) Survival 17/24 (71%) P <

20 Protective ventilation VT=6ml/kgr P plateau <40 cmh 2 O P plateau -PEEP < 20 cmh2o 20

21 Actuarial 28-Day Survival among 53 Patients with the Acute Respiratory Distress Syndrome Assigned to Protective or Conventional Mechanical Ventilation Amato M et al. N Engl J Med 1998;338:

22 N Engl J Med 2000;342: ARDS (n = 861) RANDOMIZATION Protective Ventilation (n = 432) Traditional Ventilation (n = 429) 22

23 PBW = 50 + [Height (cm) 152.4] 0.91, M PBW = [Height (cm) 152.4] 0.91, F The Acute Respiratory Distress Syndrome Network. N Engl J Med 2000;342:

24 High versus low tidal volume 24

25 What is the PEEP we should use for patients with ARDS? 25

26 26

27 N Engl J Med 2004;351: ARDS (n = 549) RANDOMIZATION PEEP = 13.2±3.5 cm H2O (n = 276) PEEP = 8.3±3.2 cm H2O (n = 273) 27

28 Lower or Higher Levels of PEEP in ARDS? The National Heart, Lung, and Blood Institute ARDS Clinical Trials Network,. N Engl J Med 2004;351:

29 PEEP in ALI / ARDS Mercat et al. JAMA 2008;299: Vt = 6 ml/kg, PEEP = 5-9 Vt = 6 ml/kg, PEEP titrated to Ppl =

30 Copyright restrictions may apply. Mercat, A. et al. JAMA 2008;299:

31 Copyright restrictions may apply. Mercat, A. et al. JAMA 2008;299:

32 Mercat, A. et al. JAMA 2008;299: Copyright restrictions may apply. 32

33 Day 28 Mortality Rates in Patients With Acute Lung Injury and Acute Respiratory Distress Syndrome Mercat, A. et al. JAMA 2008;299: Copyright restrictions may apply. 33

34 PEEP in ALI / ARDS Meade et al. JAMA 2008;299: Vt = 6 ml/kg, PEEP titrated to Ppl = (n = 508) Vt = 6 ml/kg, PEEP titrated to Ppl 40 (n = 475) 34

35 Probabilities of Survival and Unassisted Breathing From Day of Randomization (Day 0) to Day 75 Among Patients in the Lung Open Ventilation and Control Groups Copyright restrictions may apply. Meade, M. O. et al. JAMA 2008;299:

36 Is ithe potential role of driving pressure Pplateau-PEEP 36

37 Relative Risk of Death in the Hospital across Relevant Subsamples after Multivariate Adjustment Survival Effect of Ventilation Pressures. Amato MBP et al. N Engl J Med 2015;372:

38 Relative Risk of Death in the Hospital versus ΔP in the Combined Cohort after Multivariate Adjustment. Amato MBP et al. N Engl J Med 2015;372:

39 Prone position 39

40 Gattinoni et al N Engl J Med 2001;345:

41 Effects of Prone Position on outcome 76 ARDS pts (PaO2/FiO2<200) VΤ ml/kg Early implementation ~ 13h/24h Until weaning criteria were met 15% absolute reduction in ICU mortality Mancebo et al AJRCCM

42 Original Article Prone Positioning in Severe Acute Respiratory Distress Syndrome Claude Guérin, M.D., Ph.D., Jean Reignier, M.D., Ph.D., Jean-Christophe Richard, M.D., Ph.D., Pascal Beuret, M.D., Arnaud Gacouin, M.D., Thierry Boulain, M.D., Emmanuelle Mercier, M.D., Michel Badet, M.D., Alain Mercat, M.D., Ph.D., Olivier Baudin, M.D., Marc Clavel, M.D., Delphine Chatellier, M.D., Samir Jaber, M.D., Ph.D., Sylvène Rosselli, M.D., Jordi Mancebo, M.D., Ph.D., Michel Sirodot, M.D., Gilles Hilbert, M.D., Ph.D., Christian Bengler, M.D., Jack Richecoeur, M.D., Marc Gainnier, M.D., Ph.D., Frédérique Bayle, M.D., Gael Bourdin, M.D., Véronique Leray, M.D., Raphaele Girard, M.D., Loredana Baboi, Ph.D., Louis Ayzac, M.D., for the PROSEVA Study Group N Engl J Med Volume 368(23): June 6,

43 Study Overview Placing patients who require mechanical ventilation in the prone rather than the supine position improves oxygenation. In this trial, the investigators found a benefit with respect to all-cause mortality with this change in body position in patients with severe ARDS. 43

44 Enrollment, Randomization, and Follow-up of the Study Participants. Guérin C et al. N Engl J Med 2013;368:

45 Kaplan Meier Plot of the Probability of Survival from Randomization to Day 90. Guérin C et al. N Engl J Med 2013;368:

46 Characteristics of the Participants at Inclusion in the Study. Guérin C et al. N Engl J Med 2013;368:

47 Ventilator Settings, Respiratory-System Mechanics, and Results of Arterial Blood Gas Measurements at the Time of Inclusion in the Study. Guérin C et al. N Engl J Med 2013;368:

48 Primary and Secondary Outcomes According to Study Group. Guérin C et al. N Engl J Med 2013;368:

49 Conclusions In patients with severe ARDS, early application of prolonged pronepositioning sessions significantly decreased 28-day and 90-day mortality. 49

50 Positive end-expiratory pressure (PEEP) is used to improve oxygenation in patients with acute lung injury or the acute respiratory distress syndrome In this pilot trial, the investigators show that adjusting PEEP with the use of measurements of esophageal pressure to estimate transpulmonary pressure leads to improved oxygenation as compared with the conventional approach to ventilator management 50

51 Respiratory Measurements at Baseline and at 24, 48, and 72 Hours in the Control and Esophageal-Pressure-Guided Groups Talmor D et al. N Engl J Med 2008;359:

52 Respiratory Measurements at Baseline and at 24, 48, and 72 Hours in the Control and Esophageal-Pressure-Guided Groups Talmor D et al. N Engl J Med 2008;359:

53 Clinical Outcomes Talmor D et al. N Engl J Med 2008;359:

54 54

55 Neuromuscular blockers in ARDS Papazian et al NEJM 2010:363 55

56 Neuromuscular blockers in ARDS Papazian et al NEJM 2010:363 56

57 Ventilatory Strategies. Slutsky AS, Ranieri VM. N Engl J Med 2013;369:

58 Potential complication of CMV: Ventilator-Induced Diaphragmatic Dysfunction Loss of diaphragmatic force generating capacity that is specifically related to the use of controlled mechanical ventilation Vassilakopoulos & Petrof, AJRCCM 2004;169:

59 Contractility declines in humans Jaber et al. Am J Respir Crit Care Med 2011; 183:

60 Is neural transmission impaired? Radell P. et al, Intensive Care Med 2002;28:

61 Contractile dysfunction resides within the diaphragmatic muscle 61

62 Mechanisms of contractile dysfunction Muscle Atrophy Oxidative Stress Structural Injury Mitochondrial dysfunction 62

63 Mechanisms of contractile dysfunction Muscle Atrophy Oxidative Stress Structural Injury Mitochondrial dysfunction 63

64 Atrophy: fiber size Levine S et al. N Engl J Med 2008;358:

65 Jaber et al, Am J Respir Crit Care Med 2011;183:

66 Muscle Atrophy Protein synthesis Proteolysis 66

67 Protein Synthesis Shanely RA et al. Am J Respir Crit Care Med 2004;170:

68 Proteolysis Calpains Proteasome Autophagy- lysosomal proteases 68

69 Calpain Activation Jaber et al, Am J Respir Crit Care Med 2011;183:

70 Calpains degrade proteins partially Calpains render proteins anemable to proteasome degradation Shanely RA et al. Am J Respir Crit Care Med 2002;166:

71 Proteasome 71

72 26S Proteasome 72

73 26S Proteasome degrades hydrophobic proteins 73

74 26S proteasome is upregulated in humans after CMV Levine S et al. N Engl J Med 2008;358:

75 26S proteasome is preferentially upregulated in the diaphragm in humans after CMV Hussain S et al, Am J Respir Crit Care Med 2010; 182:

76 Ubiquitinated proteins are upregulated in the human diaphragm after CMV Jaber et al, Am J Respir Crit Care Med 2011;183:

77 Ubiquitinated proteins are upregulated in the human diaphragm after CMV Levine S et al, Am J Respir Crit Care Med 2011;183:

78 78

79 Hussain S et al, Am J Respir Crit Care Med 2010; 182:

80 Autophagosome formation in the human diaphragm after CMV Hussain S et al, Am J Respir Crit Care Med 2010; 182:

81 Autophagy increases with time on CMV Hussain S et al, Am J Respir Crit Care Med 2010; 182:

82 Mechanisms of contractile dysfunction Muscle Atrophy Oxidative Stress Structural Injury Mitochondrial dysfunction 82

83 Oxidized proteins are upregulated in the diaphragm after CMV Hussain S et al, Am J Respir Crit Care Med 2010; 182:

84 20S Proteasome degrades oxidized proteins 84

85 Contractile proteins are targets of oxidative stress Zergeroglu et al. J Appl Physiol 2003;95:

86 Actin and myosin are reduced in VIDD Levine et al. Am J Respir Crit Care Med 2011;183:

87 Mechanisms of contractile dysfunction Muscle Atrophy Oxidative Stress Structural Injury Mitochondrial dysfunction 87

88 Ultrastructural injury Lipid droplets Abnormal mitochondria Abnormal myofibrils Vacuoles Zhu E. et al, J Appl Physiol 2005;99:

89 Jaber et al, Am J Respir Crit Care Med 2011;183:

90 Force decline is proportional to injury Sassoon C. et al, J Appl Physiol 2002;92:

91 Mechanisms of contractile dysfunction Muscle Atrophy Oxidative Stress Structural Injury Mitochondrial dysfunction 91

92 CMV results in lipid accumulation in the diaphragm Energy oversupply Picard M et al. Am J Respir Crit Care Med 2012;186:

93 CMV downregulates the energy sensor enzyme AMPK energy oversupply Picard M et al. Am J Respir Crit Care Med 2012;186:

94 CMV impairs mitochondrial function Picard M et al. Am J Respir Crit Care Med 2012;186:

95 Summary: mechanisms of VIDD Muscle Atrophy Oxidative Stress Structural Injury Mitochondrial dysfunction Vassilakopoulos T, Intensive Care Med 2008;34:

96 Do partial support modes of mechanical ventilation cause VIDD? 96

97 Assist Control Ventilation Sassoon C et al. Am J Respir Crit Care Med 2004;170:

98 Pressure Support prevents CMV-induced diaphragmatic proteolysis Futier et al Crit Care 2008:12:R116 98

99 High level pressure support delays VIDD onset 99 Hudson et al Crit Care Med 2012; 40:

100 High level pressure support leads to VIDD Hudson et al Crit Care Med 2012; 40:

101 Adaptive Support Ventilation Prevents Ventilator-induced Diaphragmatic Dysfunction Jung, et al Anesthesiology. 112(6):

102 When to suspect VIDD Patient who fails to wean Controlled Mechanical Ventilation (CMV) ICU-Acquired Paresis excluded Prolonged neuromuscular blockade: TOF Critical Illness Polyneuropathy & Myopathy: ENG, EMG, muscle biopsy VIDD may coexist or aggravate ICUAP 102

103 How could VIDD be potentially prevented if CMV is used? 103

104 Antioxidants: Vit E analogue & contractility Betters J et al. Am J Respir Crit Care Med 2004;170:

105 Antioxidants: apocynin, NADPH oxidase inhibitor McClung, et al, Critical Care Medicine. 37: ,

106 Antioxidants: SS-31, a mitochondrial specific antioxidant SS-31 antioxidant Szeto-Schiller peptide 31 (D-Arg-2,6-dimethyl-Tyr-Lys-Phe-NH 2 ) Powers SK et al Crit Care Med 2011;39:

107 Antioxidants in mechanically ventilated patients 7 Days * * Control Antioxidants Vit E 1000 IU q8h Vit C 1000 mg q8h 0 Duration of MV ICU length of stay Nathens A et al Annals of Surgery 2002;236:

108 Antioxidant nutrients: a systematic review of trace elements and vitamins in the critically ill patient Conclusions: Trace elements and vitamins that support antioxidant function are safe and may be associated with a reduction in mortality in critically ill patients Heyland D et al, Intensive Care Med 2005;31:

109 How to prevent VIDD Use assisted modes of mechanical ventilation Try antioxidant supplementation when CMV is inevitable Sepsis? CIPNM? More studies are needed 109

110 Non Invasive Mechanical Ventilation 110

111 Non-invasive ventilation during exacerbations to avoid intubation 111

112 112

113 Brochard et al. NEJM 1995;333:

114 Intubation rate in patients with acute exacerbation of COPD treated with and without NIPPV % of patients n=16 n=15 26 n=43 n=42 NIPPV Control 0 Kramer et al 1995 Brochard et al

115 Brochard et al. NEJM 1995;333:

116 Hospital stay (days) of patients with acute exacerbation of COPD treated with and without NIPPV * NIPPV Control Brochard et al. NEJM 1995;333:

117 In-hospital mortality (%) in patients with acute exacerbation of COPD treated with and without NIPPV % of patients n=30 n=30 n=43 n=42 NIPPV Control 0 Bott et al 1993 Brochard et al

118 Early use of NIPPV for acute exacerbation of COPD on general wards % of patients NIPPV Control 5 n=118 n=118 n=118 n=118 0 Need for intubation In-hospital mortality Plant et al. Lancet 2000;355:

119 NIV in hypercapnic encephalopathy Scala et al, Intensive Care Med 2007;33:

120 Non Invasive Ventilation as weaning technique in COPD patients who fail SBT after 2 days of MV Control NIV Nava et al. Ann Intern Med 1998;128:

121 60 days mortality (%) in patients with acute exacerbation of COPD using NIPPV as a weaning technique 40 % of patients * NIPPV Control 5 0 Nava et al. Ann Intern Med 1998;128:

122 Non Invasive Ventilation during persistent (3 days) spontaneous breathing trial failure NIV NIV COPD 25/43 patients Ferrer et al. Am J Respir Crit Care Med 2003;168:

123 Non-Invasive Ventilation (n.114) Conventional Therapy (n.107) Absolute Risk Difference Relative Risk (95% CI) p-value Mortality 25% 14% 11.4% ( ) 1.75 ( ) 0.05 Reintubation 49% 49% 0% 0.99 ( ) ns 123

124 Did this RCT killed NIV? 124

125 /9 Mortality % /14 General COPD /114 * 15/107 0 NIV Standard therapy Esteban, A. et al. N Engl J Med 2004;350:

126 NIV to prevent extubation failure in patients with successful SBT Αναπνευστική ανεπάρκεια 33% 16% Ferrer et al. Am J Respir Crit Care Med 2006;173:

127 Survival of patients receiving NIV to prevent extubation failure in patients with successful SBT subgroup analysis Ferrer et al. Am J Respir Crit Care Med 2006;173:

128 Ferrer et al, Lancet 2009;374:

129 NIV after extubation in patients who develop hypercapnia during a spontaneous breathing trial Ferrer et al, Lancet 2009;374:

130 Time elapsed from extubation to development of respiratory failure NIV immediately after extubation in patients who develop hypercapnia during a spontaneous breathing trial Ferrer et al, Lancet 2009;374:

131 Thank you for your attention 131

132 There are no faculty disclosures for this session. Faculty disclosures 132