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Monday, October 31, 2005 Acute Lung Injury and ARDS SLIDE PRESENTATIONS 10:30 AM - 12:00 PM ALVEOLAR FLUID REABSORPTION IS IMPAIRED BY HYPER- CONCLUSION: Large intraoperative Vt and larger volumes of intra- CAPNIA INDEPENDENTLY OF EXTRACELLULAR AND IN- venous fluids during pneumonectomy are associated with an increased TRACELLULAR PH risk of post-operative respiratory failure. Arturo Briva MD* Lynn Welch BS Jiwang Chen PhD Pavlos Myrianthefs CLINICAL IMPLICATIONS: Potentially harmful intraoperative MD Zaher Azzam MD Emilia Lecuona PhD Vidas Dumasius BS Daniel ventilatory settings, in particular large tidal volumes, should be avoided Batlle MD Yosef Gruenbaum PhD Jacob I. Sznajder MD Northwestern during pneumonectomy. University, Chicago, IL DISCLOSURE: Evans Ferna´ndez, None. PURPOSE: Alveolar epithelium is exposed to high CO2 tensions (hypercapnia) in patients with COPD and during permissive hypercapnia in mechanically ventilated subjects. Recently, some reports propose that hypercapnia could be beneficial in the treatment of ALI/ARDS. However, more recently new data has been presented suggesting that hypercapnia may have deleterious effects on the pulmonary epithelium. The objective of our investigation was to determine the effects of hypercapnia on alveolar epithelial function. METHODS: Alveolar fluid reabsorption (AFR) was assessed during hypercapnia with normal and acid pH as compared to metabolic acidosis in the isolated rat lung model. In parallel, Na,K-ATPase activity and protein abundance in alveolar type II cell cultures was evaluated. RESULTS: Hypercapnia decreased AFR by ϳ 60% (pCO2 ϳ 80 mmHg, pH ϭ 7.15). With high pCO2 even at normal pH (7.40) alveolar fluid reabsorption was decreased but not during metabolic acidosis (pH 7.2 and normal PCO2). The deleterious effect of hypercapnia on AFR was not associated with changes of intracellular pH and reversed when pCO2 was normalized. The Na,K-ATPase activity and protein abundance was decreased in alveolar epithelial cells exposed to hypercapnia but not metabolic acidosis. CONCLUSION: Our data suggest that hypercapnia but not metabolic acidosis impairs alveolar fluid reabsorption via an endocytosis-mediated process of the Na,K-ATPase in alveolar epithelial cells leading to de- creased Na,K-ATPase activity. CLINICAL IMPLICATIONS: We reason that permissive hypercap- METHYLPREDNISOLONE INFUSION IN PATIENTS WITH nia may have deleterious effects on alveolar epithelial function and the EARLY ACUTE RESPIRATORY DISTRESS SYNDROME (ARDS) ability of the lungs to clear edema in mechanically ventilated patients. SIGNIFICANTLY IMPROVES LUNG FUNCTION: RESULTS OF DISCLOSURE: Arturo Briva, None. A RANDOMIZED CONTROLLED TRIAL (RCT) Gianfranco U. Meduri MD* Emmel Golden MD Amado X. Freire MD Edwin Taylor MD Mohamad Zaman MD Stephanie J. Carson MD Mary INTRAOPERATIVE TIDAL VOLUME AS A RISK FACTOR FOR Gibson MD Reba Umberger MD University of Tennessee Health Science REPIRATORY FAILURE AFTER PNEUMONECTOMY Center, Memphis, TN Evans R. Ferna´ndez MD* Mark T. Keegan MD Daniel R. Brown MD Francis C. Nichols MD Rolf D. Hubmayr MD Ognjen Gajic MD Mayo PURPOSE: To determine the effects of prolonged methylprednisolone Clinic, Rochester, MN infusion (PMPI) in patients with early ARDS. METHODS: Patients were stratified by medical and surgical ARDS. PURPOSE: Clinical and experimental studies identified large tidal Treatment: methylprednisolone (MP) loading 1 mg/kg I.V. was followed volume (Vt) as an important risk factor for development of acute by PMPI at 1 mg/kg/day (days 1-14), 0.5 mg/kg/day (days 15-21), 0.25 respiratory failure and acute lung injury (ALI). Patients undergoing mg/kg/day (days 22-25), and 0.125 mg/kg/day (days 26-28). Patients failing pneumonectomy may be at particular risk for adverse ventilator settings to improve lung injury score (LIS) by study day 7-9(unresolving ARDS) during surgery. We hypothesized that larger intraoperative Vt may be received open label MP (2mg/kg/day) treatment as previously reported associated with postoperative respiratory failure in patients undergoing (JAMA 1998; 280: 159). Infection surveillance and avoidance of paralysis pneumonectomy. were integral components of the protocol. The primary end-point to METHODS: We reviewed the electronic medical records of all terminate the study was a 1-point reduction in lung injury score (LIS) by patients having elective pneumonectomy at our institution from January study day 7. 1999 to January 2003. In addition to intraoperative Vt, we collected data RESULTS: 91 patients entered the study (intention to treat - ITT)and on demographics, comorbities, neoadjuvant chemotherapy and radiother- 79 were eligible for analysis (55 treated and 24 control) on study day 7.The apy, pulmonary function tests, operative procedures, duration of surgery two groups had similar characteristics at study entry (Table 1). By day 7 and intraoperative fluid administration. Respiratory failure was defined as (Table 2), the response of the two groups clearly diverged with almost the need for mechanical ventilation for greater than 48 hours postopera- twice the proportion of treated patients achieving a1-point reduction in tively or the need for reinstitution of mechanical ventilation after extuba- LIS (69.8% vs. 37.5%; P ϭ 0.002)and about 50%more treated patients tion. breathing without assistance (53.9% vs. 25.0%; P ϭ 0.01). Treated RESULTS: Of 170 consecutive pneumonectomy patients, 30 (18%) patients had a significant reduction in C-reactive protein levels and by day developed post-operative respiratory failure. Causes of respiratory failure 7 had significantly lower LIS and multiple organ dysfunction syndrome were ALI in 15 patients (50%), cardiogenic edema in 5 (17%), pneumonia (MODS) score. Treatment was associated with a reduction in the duration in 7 (23%), bronchopleural fistula in 2 (7%) and pulmonary thromboem- of MV, ICU staynd ICU mortality. The treatment group developed more bolism in 1 (3%). Patients who developed respiratory failure were frequently hyperglycemia (52.5% vs. 28.6%; P ϭ 0.06), and polyneurop- ventilated with larger intraoperative Vt than those who did not (median athy (2 vs. 0). Among treated patients, infection surveillance identified 8.3 vs 6.7 mL/kg predicted body weight, pϽ0.001, Figure). In a multvari- most nosocomial infections (65%) in the absence of fever. ate logistic regression analysis, larger intraoperative Vt (odds ratio 1.45 for CONCLUSION: PMPI was associated with significantly improved each mL/Kg of predicted body weight, 95% CI 1.12-1.92,) and larger lung function and reduced duration of mechanical ventilation. These volumes of intraoperative fluid (odds ratio 1.47 per liter of fluid infused, findings are consistent with the effects of prolonged glucocorticoid 95% CIϭ1.00-2.18), were identified as risk factors of postoperative treatment previously reported in patients with unresolving ARDS (2 respiratory failure. The 60-day mortality rate after pneumonectomy was RCTs)and severe community-acquired pneumonia (AJRCCM 2005; 171; 7.6% (13 of 170 patients), with respiratory failure accounting for 46% of 242-248). the deaths. Patients who developed post-operative respiratory failure had CLINICAL IMPLICATIONS: The findings of this study support the longer hospital length of stay (31.5 Ϯ 10.4 days vs. 7.8 Ϯ 1.3 days; p use of PMPI in association with infection surveillance and avoidance of Ͻ0.001). paralysis in patients with ARDS. CHEST / 128/4/OCTOBER, 2005 SUPPLEMENT 129S Monday, October 31, 2005 Acute Lung Injury and ARDS, continued hitory of blast injury. The CT studies were reviewed by two staff Table 1—Baseline Characteristics radiologists and characterized as well as graded into the following categories: pulmonary contusion, pneumothorax, consolidation, atelecta- Variable Methylpr. Placebo P value sis, effusions, ARDS, and injuries of the chest wall, cardiac, vascular, airway or extrathoracic compartments. No. of Patients 55 24 Age, years * 49.6 53.3 0.34 Male gender (%) # 30 (54.6) 11 (45.8) 0.48 APACHE III score ICU entry 58.9 55.0 0.43 APACHE III score study entry 57.6 62.8 0.28 Direct cause of ARDS (%) 40 (72.7) 14 (58.3) 0.21 Sepsis-induced ARDS (%) 42 (76.4) 22 (91.7) 0.13 Presence of Shock (%) 11 (20.0) 8 (33.3) 0.20 Lung Injury Score 3.23 3.14 0.44 PaO2:FiO2 117.4 129.2 0.52 MODS score 1.91 1.92 0.96 C-reactive protein 27.4 25.9 0.33 DISCLOSURE: Gianfranco Meduri, None. RESULTS: Of 196 war patients identified, 83 documented blast injury patients were selected. Thirty seven patients had pulmonary contusions; TRANSFUSION RELATED PULMONARY EDEMA IN THE IN- associated findings from this group include 23 patients with chest TENSIVE CARE UNIT (ICU) wall/musculoskeletal injuries, 21 with pneumothorax and 20 with effu- Rimki Rana MD* Sameer Rana MD Evans R. Ferna´ndez MD Syed A. sions. The most common manifestations of 86 patients were effusions (58) Khan MD Ognjen Gajic MD Mayo Clinic, Rochester, MN and atelectasis (46). Of the 58 patients with effusions, 55 had associated extrathoracic injuries including extremities (32), abdomen/pelvis (27), PURPOSE: The reported incidence of transfusion related acute lung head (18) and others (3). Other pulmonary manifestations include con- injury (TRALI) varies due to the lack of standardized definition. Using the solidation/airspace disease (24), ARDS (9), PE (6), documented infections Toronto Consensus Panel definition, we aimed to describe the incidence (4) and presumed fat emboli (2). Non-pulmonary manifestations include of TRALI, possible TRALI and transfusion