Systemic Inflammatory Response and Protective Ventilation Strategies

1. Systemic Inflammatory Response and Protective Ventilation Strategies Daniel R. Brown, PhD, MD, FCCM Chair, Division of Critical Care Medicine Associate Professor Department of Anesthesiology Rochester, Minnesota USA Director, Critical Care Practice Mayo Clinic brown.daniel@mayo.edu

2. Conflict of Interest • None • ARDSNet Investigator

3. Learning Objectives • Identify ventilator management strategies associated with improved outcomes • Describe the association between mechanical ventilation and inflammation • Discuss strategies to provide optimal mechanical ventilation

4. Why be concerned about perioperative inflammation? • Dysregulation of inflammation may have a profound impact on morbidity and mortality • An inexact science; genetic factors likely play a role • Inflammatory risk from anesthesia and surgery may be modified

5. Time, Feb 23, 2004

6. Dysregulation of inflammation • Too little inflammation • Increase susceptibility to infection • Concerns regarding tissue remodeling and tissue repair • Cancer recurrence? • Too much inflammation • End-organ dysfunction • May lead to permanent dysfunction • Cancer recurrence?

7. BALF IL-6 PC 20 cm H2O VT ~15 mL/kg J Surg Research 2013; 180: 125-32

8. Some points to consider... • Mechanical ventilation in and of itself may harm people (VILI) • Many observations in ICU patients likely apply to OR patients • Many observations in patients with acute lung injury may apply to patients with healthy lungs

9. Back in the day… • Supraphysiologic tidal volumes thought necessary to prevent hypoxemia • Bendixen HH et al. NEJM 1963; 269: 991-6 • High airway pressures shown in animal models to be injurious to lung parenchyma Dreyfuss 1985

10. Balancing Ventilation Priorities Overdistention Derecruitment • Consequences: • Atelectasis • Hypoxemia • Hypercapnia • Inflammation • Consequences: • VQ mismatch • Barotrauma • Alveolar-capillary injury • Inflammation

12. Predicted Body Weight ARDSNET NEJM 2000; 342: 1301-8

13. Cytokine, Inflammation and Tidal Volumes Parsons PE et al. Crit Care Med 2005; 33: 1-6

15. Talmor D et al. NEJM 2008; 359: 2095-104

16. 332 ICU patients without lung injury at onset of mechanical ventilation • 80 developed acute lung injury within 5 days • Risk factors included tidal volume, blood product transfusion, acidosis and restrictive lung disease Crit Care Med 2004; 32: 1817-24

17. Higher myeloperoxidase implies activation of polymorphonuclear cells • Supported by increased BALF IL-8 concentrations at 5 h • Higher nucleosome levels suggest pulmonary apoptotic cell death Anesthesiology 2008; 108: 46-54

18. Things we think we know about ventilating ICU patients • Supraphysiologic VT are bad • Negative end-expiratory transpulmonary pressure is not good • Protective ventilation appears to benefit both healthy and diseased lungs Villar J et al. Acta Anaesthesiol Scand 2004; 267-71

19. 3,434 cardiac surgery patients • Higher tidal volumes were independent risk factors for organ failure, multiple organ failure and prolonged ICU stay • Organ failures were associated with increased ICU length of stay as well as hospital and long-term mortality Anesthesiology 2012; 116: 1072-82

20. Anesthesiology 2012; 116: 1072-82

21. 40 elective CABG patients studied post-CPB • 10-12 ml/kg + 2-3 cm H2O PEEP • 8 ml/kg + 10 cm H2O PEEP • Plasma and BAL IL-6 and IL-8 measured before sternotomy, immediately after CPB separation and 6 h after mechanical ventilation J Thorac Cardiovasc Surg 2005; 130: 378-83

22. BAL IL-6 and IL-8 J ThoracCardiovascSurg 2005; 130: 378-83

23. Plasma IL-6 and IL-8 J Thorac Cardiovasc Surg 2005; 130: 378-83

24. 52 esophagectomy patients with protective strategy during one-lung ventilation • 9 ml/kg during 2 lung ventilation • 9 ml/kg vs. 5 ml/kg during one-lung ventilation • Blood IL-1β, IL-6, IL-8 and TNF-α before, during and 18 hours after surgery

25. Ventilator ManagementDuring Esophagectomy • Lower IL-1β, IL-6, and IL-8 after one-lung ventilation and 18 h post-op with lower one-lung VT • No difference in TNF-α Anesthesiology 2006; 105: 911-9

26. Ventilator ManagementDuring Esophagectomy • Higher PaO2/FIO2 during one-lung ventilation and following surgery in protective group • Shorter time to extubation in protective group (115 vs. 171 min) • Less extravascular lung water increase Anesthesiology 2006; 105: 911-9

27. 32 elective thoracic surgery patients • VT 10 ml/kg vs. 5 ml/kg during and after OLV • BAL fluid of ventilated lung 30 minutes after intubation, after OLV and 2 h postoperatively • Proinflammatory variables increased in all patients; increases were less in some cytokines with smaller OLV VT Anesth Analg 2005; 101: 957-65

28. 400 prospective, randomized abdominal surgery patients • Less major pulmonary and extrapulmonary complications • Shorter ICU LOS Futier E et al. 2013; 369: 428-37

29. Data would suggest during mechanical ventilation in the OR • Mechanical ventilation contributes to inflammation • How a patient is ventilated modifies the inflammatory response • Intraoperative mechanical ventilation strategy impacts postoperative outcome

30. Does it make a difference if we use a volume or pressure regulated mode?

31. Lower tidal volumes and plateau pressures seem to be protective P Plat 30 23 21 16 Frank JA, et al. AJRCCM 2002; 165: 242-9

32. Day 1 plateau pressure and mortality in ARDSNET study Hager DN, et al. AJRCCM 2005; 172: 1241-4

33. Should PPlat target be < 30? • 30 ARDS pts receiving low 6 mL/kg IBW • CT evaluation for hyperinflation • Solid circles indicate hyperinflation • Cytokines lower and ventilator-free days greater in protected group Terragni PP, et al. AJRCCM 2007; 175: 160-6

34. Neonatal Systematic Review Favors volume over pressure controlled mode Peng WS et al. doi:10.1136/archdischild-2013-304613

35. Risk Overdistension Injury PEEP Airway Closure Risk Goals of Ventilator Management