James S. Allan, M.D. April 27, 2014 (no disclosures)

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Post-Pneumonectomy Pulmonary Edema James S. Allan, M.D. April 27, 2014 (no disclosures)

Definition Post-Pneumonectomy Pulmonary Edema First described experimentally in 1942 by Gibbon* Acute hypoxic syndrome following pulmonary resection Commonly after pneumonectomy (esp. on right ), but can occur after lesser pulmonary resections Syndrome is congruent with ARDS and ALI Infiltrates on chest imaging PaO 2 /F i O 2 <300 (ALI) or <200 (ARDS) PCWP <18mmHg (non-cardiogenic) *Gibbon JH. Surgery 1942; 12:694. Turnage WS. Chest 1993; 103:1646. 2

Incidence and Mortality Post-Pneumonectomy Pulmonary Edema Most recent incidence reported at 3.1% (*STS database), with previous series ranging from 4-7% Rates of ARDS following open lobectomy range from 1-4%, and <1% following VATS resections Mortality of PPE has been consistently reported between 50 100% *Shapiro M. Ann Thorac Surg 2010; 90:927. 3

Clinical Presentation (1) Post-Pneumonectomy Pulmonary Edema 35% of patients show first signs within 24 hours of resection, with most patients presenting within the first three post-operative days. Presentation after POD 7 is rare. Presentation is often rapid, with intubation being needed in under 24 hours from initial signs of deterioration 4

Clinical Presentation (2) Post-Pneumonectomy Pulmonary Edema Early signs Tachypnea Low-grade temperature Increasing O 2 requirement Hypocarbia Later signs Progressive hypoxia refractory to O 2 therapy Hypercarbia Radiographic findings 5

Radiographic Appearance Post-Pneumonectomy Pulmonary Edema PPE is non-cardiogenic Infiltrates are patchy and diffuse, as opposed to peri-hilar and confluent 6

Pathophysiology Starling forces and the lymphatic system In conditions of homeostasis, there is a balance of hydrostatic forces (working to force fluid into the interstitium) with oncotic forces (trying to keep water within the circulatory system). The lymphatic system scavenges interstitial fluid and returns it to central circulation. Lymphatic drainage 7

Pathophysiology Alteration of Starling forces Pneumonectomy results in entire cardiac output being forced through a diminished capillary bed, which leads to increased transcapillary filtration. Lymphatic drainage 8

Pathophysiology Alteration of lymphatic function. Disruption of lymphatic drainage from surgical resection or radiation fibrosis further impairs the return of extracellular fluid to the circulation. Lymphatic drainage 9

Pathophysiology Loss of capillary and alveolar integrity (1) Dysregulation of Starling forces alone should only lead to transudative pulmonary edema. However, many studies have shown that the edema fluid in PPE has a high protein content.* These findings point to a loss of capillary and alveolar wall integrity that is better characterized as a panendothelial, pan-epithelial injury. 10 *Turnage WS. Chest 1993; 117:999.

Pathophysiology Loss of capillary and alveolar integrity (2) Barotrauma from positive pressure ventilation, especially collapse/re-inflation, is a significant cause of breakdown of the capillary-alveolar interface. Large intra-operative tidal volumes have been shown to correlate with PPE.* 11 *Fernandez-Perez ER. Anesthesiol 2006; 105:14.

Pathophysiology Loss of capillary and alveolar integrity (3) Inflammatory mediators consequent to surgical manipulation and underlying disease also contribute to disruption of the capillary-alveolar complex. Markers of oxidative stress (ischemia-reperfusion injury) are also elevated during single lung-ventilation.* Plasma protein thiols (antioxidants): 18% reduction Protein carbonyls (indicator of oxidative damage): 26% increase Neutrophil myeloperoxidase (enzyme that generates ROS): 100% increase Williams EA. Eur Resp J 1998; 11:1028 12

Predictors of Risk Post-pneumonectomy pulmonary edema Right pneumonectomy Carinal resection High intra-operative tidal volumes High peri-operative fluid administration High post-op urine output Length of time under single-lung ventilation Post-op lung hyperexpansion Use of blood products (TRALI) Pre-op radiotherapy and chemoradiotherapy 13

Prevention Post-pneumonectomy pulmonary edema Patient selection Age, performance status, co-morbidities PFTs and extent of functional resection Neoadjuvant therapy Intra-operative and peri-operative management Single-lung anesthesia Conduct of surgery Fluid management 14

Prevention Post-pneumonectomy pulmonary edema Single-lung anesthesia Proper, stable tube position Bronchoscopy Mouth pack Lower tidal volume, raise rate, and use a little PEEP while on single-lung ventilation ARDSNet 2 or half as much; twice as fast Pressure-controlled or pressure-limited mode No over-pressure events 15

Prevention 16 Post-pneumonectomy pulmonary edema Conduct of surgery Minimize operative time and operative trauma. Minimize single-lung ventilation time. Avoid repetitive collapse and re-expansion of both the operative and non-operative lung. Keep PVR low by addressing atelectasis, avoiding hypercapnia/hypoxia, and limiting use of pressors. Minimize blood loss. Use balanced chest drainage to prevent overexpansion of remaining lung.

Prevention Post-pneumonectomy pulmonary edema Fluid management Avoid hyperdynamic state with fresh pneumonectomy (unfavorable Starling forces) Avoid hypotension and severe anemia (oxidative stress) Run the pneumonectomy patient euvolemic to slightly dry ½ ml/kg/hr of urine is plenty Beware of diastolic hypotension and other causes of low urine output Consider a narcotic-only epidural 17

Treatment Post-pneumonectomy pulmonary edema Ventilatory supportive care using ARDSNet guidelines adjusted for pneumonectomy Lower tidal volume Higher rates PEEP Permissive hypercapnia Pressure-controlled or pressure-limited mode (see syllabus for protocol card) 18

Treatment Post-pneumonectomy pulmonary edema Nitric oxide Several small studies have suggested that inhaled nitric oxide therapy may be beneficial 1,2 Acts as pulmonary vasodilator Improves V/Q matching Corticosteroids Intra-operative prophylaxis 3 19 Post-operative therapy 4 ECMO 5 and ECCO 2 -R 6 1 Mathisen DJ. Ann Thorac Surg 1998;66:1894. 2 Rabkin DG. Ann Thorac Surg 2001;72:272. 3 Cerfolio RJ. Ann Thorac Surg 2003;76:1029. 4 Dünser M. Ann Thorac Surg 2004;78:335. 5 Iglesias M. Ann Thorac Surg 2008;85:237. 6 Alpard SK. Sem Surg Oncol 2000;18:183.

Post-Pneumonectomy Pulmonary Edema James S. Allan, M.D. April 27, 2014 (no disclosures)