1. Traditional One-Lung Ventilation & ALI; Have we been killing our Patients? Philip M. Hartigan, MD Brigham & Women’s Hospital Harvard Medical School

2. Case Report: 54 y/o male Smoking History COPD Persistent cough

3. CXR - Large RUL mass Cytology = NSCCA Metastatic w/u Negative Scheduled for a Right Pneumonectomy Case Report:

4. CASE REPORT: General Anesthetic: Thoracic Epidural A-Line TIVA L-DLT VT =10 ml/kg PEEP = O

5. CASE REPORT: Hospital Course – POD # 2:  Dyspnea  Hypoxemia  Pulmonary Edema

7. CASE REPORT: Hospital Course (cont.):  Respiratory Failure  Reintubation  PCWP < 16 cmH 2 O  Diuretics  Fluid Restriction  ARDS  MSOF  Death

8. What Just Happened ?

9. “ Traditional” OLV“Protective” OLV VT = 10 ml/kgVT = 6 ml/kg PEEP = 0PEEP = 5 cmH 2 O

10. Impact:Incidence: 2 - 9% Mortality: 35 – 72% “ALI/ARDS is emerging as the most prominent cause of perioperative mortality following pulmonary resection as other complications have become better controlled” Peter Slinger 2006

11. Known Causes of ALI / ARDS: Infection Aspiration BPF Cardiac Failure Pulmonary Embolic events TRALI Other (pancreatitis, trauma, CPB…)

12. Post-Pneumonectomy Pulmonary Edema ALI following Pulmonary Resection Primary ALI following Thoracic Surgery Idiopathic ALI following Pulm Resection Nomenclature

13. Hypothesis: “Traditional OLV Causes ALI “  Extrapolated Evidence  Retrospective Studies  Animal Studies  Clinical Studies

14. Extrapolated Evidence: ARDS Literature: Reduced ARDS Mortality with Protective Ventilation VILI Literature: Volutrauma Atelectrauma Inflammatory Response Alveolar Systemic

16. “The finding of small changes in cytokine concentrations is in no way indicative of a causal link with outcome” Dreyfuss Didier, 2003

17. Hypothesis: “Traditional OLV Causes ALI “  Extrapolated Evidence – (Weak)  Retrospective Studies  Animal Studies  Clinical Studies

18. Retrospective Studies; Factors Associated w/ ALI:  High Perioperative Fluid Balance  Extent of Surgery  Side of Surgery (R > L)  Duration of Surgery  Alcoholism / Chemotherapy  Increased Vent Pressures/Volumes

19. Retrospective Studies: Van der Werff ‘97 190 Pts PIPs > 40 assoc. w/ Pulm Edema Licker ‘03879 Pts Ventilatory Hyperpressure Index Fernandez -170 Pts VT assoc with -Perez ‘06Resp Failure 8.3 vs 6.7 ml/kg

21. Risk Factors for Primary ALI Licker, et al: Anesth Analg 2003;97:1558  Pneumonectomy  Excessive Fluid  Alcoholism  Ventilatory Hyperpressure Index

22. Risk Factors for Primary ALI Licker, et al: Anesth Analg 2003;97:1558  Pneumonectomy  Excessive Fluid  Alcoholism  Ventilatory Hyperpressure Index (P-Plateau > 10 cmH 2 0 x Duration OLV)

23. Hypothesis: “Traditional OLV Causes ALI “  Extrapolated Evidence - (weak)  Retrospective Studies – (weak)  Animal Studies  Clinical Studies

24. Animal Studies: De Abreu, et al. Anesth Analg 2003 Control – 2LV @ 8 ml PEEP = 2 Protect - OLV @ 4 ml PEEP = 2 Tradit’l – OLV @ 8 ml PEEP = 0

25. OLV in the Rabbit Lung Model De Abreu, et al. Anesth Analg 2003; 96:220 PIP MPAP TXB2 WG 2-LV (CTRL)Protect OLVTraditional OLV

26. Hypothesis: “Traditional OLV Causes ALI “  Extrapolated Evidence – (weak)  Retrospective Studies – (weak)  Animal Studies – (suggestive)  Clinical Studies

27. Clinical Studies: Schilling, et al 2005 Schilling, et al 2007 Schilling, et al 2011 Traditional vs Protective OLV: Proinflammatory Cytokines Inhalational Agents are protective

28. Schilling T, et al. Anesth Analg 2005;101:957 Protective OLV and Inflammatory Mediators Design: 32 Pts for thoracotomy OLV @ 5 vs 10 ml/kg PEEP = 0 BAL at 3 time points Findings: Traditional OLV was associated with: Proinflammatory cytokines Antiinflammatory cytokines I

29. IL-8TNF-a sICAM IL-10 VT = 10 ml/kgVT = 5 ml/kg Schilling ‘05

30. Schilling T, et al. Anesthesiology 2011;115:65 Effect of Volatile Anesthetics on Systemic and Alveolar Inflammatory Response Design: 63 Pts for thoracotomy 21 – Propofol (4mg/kg/hr) 21 – Desflurane (1 MAC) 21 – Sevoflurane (1 MAC) OLV @ 7 ml/kg PEEP = 5 BAL before & after OLV Findings: Desfl & Sevo attenuate proinflammatory changes even with protective OLV compared to Propofol. III

32. Hypothesis: “Traditional OLV Causes ALI “  Extrapolated Evidence – (weak)  Retrospective Studies – (weak)  Animal Studies – (suggestive)  Clinical Studies – (suggestive)

33. Death OLV Inflammatory Response ALI / ARDS

34. Death Unbalance Drainage Chemo / XRT Extent of Surgery Duration of Surg Alcoholism Genetic Unrecognized:  Infection  Aspiration  Emboli  TRALI  Cardiac Pneumonectomy Impaired Lymphatics Excessive Fluids OLV Inflammatory Response ALI / ARDS

35. Death Unbalance Drainage Chemo / XRT Extent of Surgery Duration of Surg Alcoholism Genetic Unrecognized:  Infection  Aspiration  Emboli  TRALI  Cardiac Pneumonectomy Impaired Lymphatics Excessive Fluids Low VT PEEP Sevoflurane Desflurane Low FiO2 OLV Inflammatory Response ALI / ARDS

36. CO 2 Injury The Balancing Act of OLV O2O2

38. Schilling T, et al. Br J Anaesth 2007;99:368 OLV & Inflammatory Mediators: Propofol vs Desflurane Design: 30 Pts for thoracotomy 15 – Propofol (4mg/kg/hr) 15 – Desflurane (1 MAC) OLV @ 10 ml/kg PEEP = 0 BAL at 3 time points Findings: Desflurane attenuates the proinflammatory changes of non-protective OLV II

39. TNF-a IL-8 IL-10 sICAM-1 PropofolDesflurane Schilling ‘07

42. Postulated Causes  VILI from “Traditional” OLV  Oxygen Toxicity  Hyperperfusion Stress Injury  Inflammatory Response to Surgery  Postoperative Hyperexpansion  Unrecognized, Known Etiologies

43. Known Causes of ALI / ARDS: Infection Aspiration BPF Cardiac Failure Pulmonary Embolic events TRALI VILI Other (pancreatitis, trauma, CPB…)

48. Factors Associated with ALI  High Perioperative Fluid Balance  Extent of Surgery  Side of Surgery (R > L)  Duration of Surgery  Alcoholism / Chemotherapy

50. Idiopathic ALI following Pulm Resection  2-9% following pneumonectomy  35 – 50% Mortality  Clinical / Histology resembles ALI/ARDS  Low PCWP, high alveolar protein  Diagnosis of Exclusion

51. Acute Lung Injury Bilateral Pulmonary Infiltrates PCWP < 18 mmHg PaO 2 /FiO 2 < 300 mmHg ARDS PaO 2 /FiO 2 < 200 mmHg Definitions: ALI & ARDS

52. Hypothesis: “Traditional OLV Causes ALI “  Extrapolated Evidence  Retrospective Studies  Animal Studies  Clinical Studies

53. OLV Mech Stress Injury ALI ARDS DEATH Inflamm Mediators

55. Perspective Does Traditional OLV Cause ALI ? Potential contributing factor Theoretical risk Not currently strongly supported by evidence

56. Recommendations: Initial VT = 5-6 ml/kg PEEP = 5