pneumonectomy and ards hartford hospital icu m&m joshua dill, do pgy-iii henry igid, md pgy-ii

Pneumonectomy and ARDS

Hartford Hospital ICU M&MJoshua Dill, DO PGY-IIIHenry Igid, MD PGY-II

Morbidity & Mortality ConferenceMorbidity & Mortality Conference

It is for the department faculty and residents to peer review case(s) from the inpatient service.

The primary objective is to improve overall patient care focusing on quality of care delivered, performance improvement, patient safety and risk management.

• This material is confidential and is utilized as defined in Connecticut State statute 19a-17b Section(4) for evaluating and improving the quality of health care rendered

•Goals:

To review recent cases and identify areas for improvement for (all) clinicians involved Patient complications & deaths are reviewed with the purpose of educating staff, residents and medical students. To identify ‘system issues’, which negatively affect patient careTo modify behavior and judgment and to prevent repetition of errors leading to complications. To assess all six ACGME competencies and Institute of Medicine (IOM) Values in the quality of care delivered Conferences are non punitive and focus on the goal of improved and safer patient care

•This material is confidential and is utilized as defined in Connecticut State statute 19a-17b Section(4) for evaluating and improving the quality of health care rendered

Morbidity & Mortality Conference

Morbidity & Mortality ConferenceMorbidity & Mortality Conference

•Every Defect is a TreasureEvery Defect is a Treasure


Every Defect is a TreasureEvery Defect is a Treasure

•Errors are due to:

–Processes – 80% –Individuals – 20%

•Translate all error into education•This material is confidential and is utilized as defined in Connecticut State statute 19a-17b Section(4) for evaluating and improving the quality of health care rendered

Every Defect is a TreasureEvery Defect is a Treasure

•I request those that may recognize and may have been involved in the care of patients’ being presented not to take the discussion personally…


Objectives

• Discuss the work up and evaluation for lung resection.

• Discuss the criteria, incidence, risk factors, and mortality data, and mechanisms of developing ALI/ARDS.

• Discuss cases on ARDS related to chemotherapy and lung resection.

Patient Information

• MC• 50-year-old male

• Admitted to Windam Hospital on 10/7/13– For Pneumonia

• Transferred to Hartford Hospital on 10/11/13– For Ventilator dependent respiratory failure

secondary to ARDS

Patient Information

• Recent diagnosis (2 months PTA):– Stage III Poorly Differentiated Lung

Adenocarcinoma, July 2013– s/p Mediastinoscopy, July 2013– s/p left Pneumonectomy, Aug 2013– s/p 1 cycle of chemotherapy (Cisplatin and

Pemetrexed), 6 days PTA• Family history of NHL in one brother• Daily smoker until July 2013

History of Present Illness

• Days prior to admission:– Progressive shortness of breath, subjective fevers,

worsening mental status– Had first cycle of chemotherapy 1 week prior

• Day of admission– Nausea– One episode of vomiting

Hospital Course in Windam

• At Windam Hospital ED:– HR 130s– Tmax 101.3– BP: 97/63– RR: 20– Ill appearing, crackles in left lung– WBC 3.6, Lactate 1.5– CXR: Left sided infiltrates– Admitted as a case of HCAP

Investigations

• WBC 3.6, Hgb 11.9, Hct 31.8, Plt 306• Na 131, K 3.9, Cl 93, HCO3 24, BUN 16, Crea

0.8• Anion Gap 14• CK 18, Trop 0.3• EKG: Sinus tachycardia

Investigations

• Microbiology:– Blood culture: No growth– Respiratory culture: Few neutrophils, No growth– H1N1: Negative– Influenza A and B PCR: Negative


• Started initially on Azithromycin and Ceftriaxone, then changed to Levofoxacin and Vancomycin

• Course complicated by severe sepsis and pancytopenia– Echocardiogram in Windam: • Normal EF, no pulmonary hypertension


• 3 days after admission– Intubated for worsening Hypoxemic Respiratory

Failure secondary to ARDS– ABG: 7.45/33/73 on 80% FiO2– p/f ratio 91

• 4 days after admission– Transferred to Hartford Hospital

Prior chest x-ray image Chest x-ray image on admission

Hospital Course in Hartford

• Underwent Left thoracentesis for moderate pleural effusion– Transudative effusion– Pleural Fluid: Few neutrophils, No bacterial

growth, no malignant cells• Supportive management given – Steroids (High dose, Methylprednisolone 170

mg/day initially)– Continued antibiotics (Vancomycin and Cefepime)– Furosemide boluses– Needed paralytics (Cisatracurium)

Hospital Course in Hartford

• Extubated 10/21 (total of 12 days of intubation)

• Discharged to SNF on prednisone taper and 2 L of oxygen via NC.

• ABG on discharge: pH 7.47, pCO2 41, HCO3 26, pO2 71 on 2 L of oxygen.

Chest x-ray image on admisson Chest x-ray image prior to discharge

Discussion

Evaluation for Lung Resection

• Full PFTs• Patients whose PFT results show good lung

function (ie, FEV1, > 2 L or > 60% of predicted; and DLco, > 60%) can be referred for surgery without undergoing other tests for further assessing their pulmonary status.

• Debapriya Datta, MD, Bimalin Lahiri, MD. Preoperative Evaluation of Patients Undergoing Lung Resection Surgery. CHEST 2003; 123:2096–2103

• Patients with preoperative FEV1 values < 60% of predicted and/or DLco values < 60% of predicted need further evaluation.

• They should undergo a quantitative ventilation-perfusion lung scan to estimate ppo FEV1 and predicted postoperative (ppo) DLco. If the ppo FEV1 and ppo Dlco are > 40% of predicted, surgical risk is acceptable, and surgery (including pneumonectomy) should be offered to these patients.

• Patients with ppo FEV1 and ppo Dlco values of < 40% should undergo exercise testing to evaluate pulmonary reserve and to assess the adequacy of oxygen transport.

• Cycle ergometry with incremental workloads, which measures V O ; 2 , V O ; 2 max, minute ventilation, and carbon dioxide output with concomitant monitoring of ECG, BP, oximetry, while the patient exercises to the maximal end point or to the symptom-limited maximum, is probably the best form of exercise testing.

• Patients with ppo FEV1/ DLco ratios of <40% of predicted, but with V O ; 2max values on exercise testing of > 15 mL/kg/ min, can undergo surgical resection, including pneumonectomy.

• The algorithm validated by Wyser et al using a higher cutoff of 80% of predicted for FEV1 and DLco, and incorporating exercise testing earlier in the evaluation, represents an alternative approach to evaluating patients for lung resection surgery.

Acute Respiratory Distress Syndrome• Clinical Criteria for the Diagnosis of ALI (acute lung

injury), ARDS (acute respiratory distress syndrome.)– Timing: acute– Chest Radiograph: Diffuse, bilateral infiltrates– Oxygenation • ALI Acute PaO2/FiO2 < 300 mm Hg• ARDS Acute PaO2/FiO2 < 200 mm Hg

– Pulmonary capillary wedge pressure : < 18 mm Hg

• Bernard GR, Artigas A, Brigham KL, et al and The Consensus Committee: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes an clinical trials coordination. Am J Crit Care Med 149:818-824, 1994.

The Berlin Definition (2012)

• The ARDS Definition Task Force (2012) Acute respiratory distress syndrome: the Berlin definition. JAMA 307:2526–2533

Incidence forDeveloping ALI/ARDS

• Studies indicate that ALI/ARDS occurs after 2% to 4% of pneumonectomies, 1% of lobectomies, and is estimated to be 0.1% to 0.2% after thoracoscopic surgery

• Seminars in Cardiothoracic and Vascular Anesthesia, Vol 8, No 4 (December), 2004: pp 317–334

Mortality of ALI/ARDS• Once developed, ALI and ARDS may carry a high mortality.

Death rates in surgical and medical patients from ALI/ARDS range from 53% to 74%.

• However, even the development of the less severe condition, ALI, carries a high mortality (26%–33%).

• Especially at risk are right pneumonectomy patients. Mortality has been reported to be 100% for patients who developed ALI/ARDS after a right pneumonectomy compared with 50% mortality if the patient had undergone a left pneumonectomy.

• No difference in mortality has been found with respect to the side of surgery after lobectomy.

Risks forDeveloping ALI/ARDS

• Age greater than 60 years• Male gender• Chronic suppurative disease• Concurrent cardiac disease• Low diffusion capacity for carbon monoxide• Prior radiation or chemotherapy• Remaining lung perfusion of less than 55% of total

lung perfusion• Seminars in Cardiothoracic and Vascular Anesthesia, Vol 8, No 4 (December), 2004: pp 317–334

Risks for Developing ALI/ARDS• Intraoperative factors include

– Pneumonectomy (right greater than left, carinal resection greater than noncarinal resection)

– Excessive perioperative– Intravascular volume– Extent of tissue resection– Duration of operation– Increased blood loss– reoperation.

• Postoperative associations include elevated perioperative– Fluid intake and – Nonbalanced drainage of hemithorax after pneumonectomy.


Postulated Mechanisms for ALI/ARDS • Elevated pulmonary vascular pressures • Lung capillary endothelial damage • Lymphatic disruption and surgical trauma • Acute inflammatory reaction to operative lung collapse

and re-expansion • Ischemia-reperfusion injury of operative lung • Relative oxygen toxicity and reactive oxygen species

generation • Microembolization • Volutrauma


Postulated Mechanisms for ALI/ARDS

Chemotherapy-Induced Late Acute Respiratory Distress Syndrome Following Right Pneumonectomy for

Bronchogenic CarcinomaRespir Care 2003;48(6):606–610.

• Late ( >30 day) ALI/ARDS after surgery and neoadjuvant therapy is a less well known impending severe complication after extensive resection of non-small-cell lung cancer.

• They reported 2 patients who suffered late postoperative acute respiratory distress syndrome (ARDS) that was felt to be chemotherapy-induced.

• Both patients underwent neoadjuvant combination chemotherapy prior to right pneumonectomy for primary bronchogenic carcinoma, and then suffered ARDS in the remaining lung a few weeks after surgery.

• The first occurred in a patient treated with gemcitabine, the second in a patient receiving a combination of vinorelbine and mitomycin.

• No evidence of infection or other specific ARDS etiologies could be found, whereas the bronchoalveolar lavage fluid cell differentiation and protein content suggested the permeability form of lung edema.

• Both patients had rapid clinical, functional, and radiologic improvement with high-dose corticosteroids.

• High dose corticosteroids have been described as effective in treating this but this is only anecdodal at this point. – EVANGELOS BRIASOULIS, NICHOLAS PAVLIDIS. Noncardiogenic Pulmonary Edema: An Unusual and

Serious Complication of Anticancer Therapy. The Oncologist, 2001;6:153-161.

Risk factor analysis for postoperative acute respiratory distresssyndrome and early mortality after pneumonectomy: The

predictive value of preoperative lung perfusion distribution J Thorac Cardiovasc Surg 2010;140:26-31)

Objectives•To establish the preoperative risk factors in the development of acute respiratory distress syndrome (ARDS) and early mortality after pneumonectomy for lung cancer and to examine the influence of reduced pulmonary perfusion on outcomes.

Methods•Between 1994 and 2009, of 425 patients who underwent simple pneumonectomy for primary lung cancer, 164 who were preoperatively evaluated with lung perfusion scanning formed the population of this study.

Results• Of 30 (18.3%) patients who had major pulmonary

complications, 17 (10.4%) progressed to ARDS, 15 of whom subsequently died.

• On multivariable logistic regression analyses, lower predicted postoperative forced expiratory volume in 1 second (ppo-FEV1; relative risk of 0.93 [P ¼ .020] for ARDS and 0.94 [P ¼ .027] for mortality) and greater perfusion fraction of resected lung (relative risk of 1.10 [P ¼ .003] for ARDS and 1.09 [P ¼ .002] for mortality) were found to be independent factors associated with ARDS and early mortality.

• With a cut-off value of 35% for perfusion fraction of resected lung, patients with a perfusion fraction of greater than 35% had a greater incidence of ARDS (17.3% vs 3.3%, P ¼ .005) and early mortality (19.8% vs 6.0%, P ¼ .010) than those with a perfusion fraction of 35% or less.

Conclusions• Patients with a low ppo-FEV1, a high perfusion

fraction of resected lung, or both had a higher incidence of ARDS and early mortality after pneumonectomy.

• Therefore, although the ppo-FEV1 appears to be within an acceptable limit for pneumonectomy, much attention should be given to patients with a high perfusion fraction of resected lung.

Treatment/Prevention• After the onset of respiratory failure, oxygen therapy

and ventilatory assistance must be initiated. • Noninvasive ventilation has been reported to reduce

mortality of ARDS after lung resection .– Auriant I, et al. Noninvasive ventilation reduces mortality in acute

respiratory failure following lung resection. Am J Respir Crit Care Med. 2001;164(7):1231–5.

• ARDS Net trials have demonstrated lung protective ventilation strategies improve outcomes. – Petrucci N, Iacovelli W (2007) Lung protective ventilation strategy for

the acute respiratory distress syndrome. Cochrane Database Syst Rev 3: CD003844.

• The early use of inhaled nitric oxide or other pulmonary vasodilators has been promoted.– Mathisen DJ, et al. Inhaled nitric oxide for adult respiratory distress

syndrome after pulmonary resection. Ann Thorac Surg. 1998;66(6):1894–902.

– Rabkin DG, et al. Nitric oxide for the treatment of postpneumonectomy pulmonary edema. Ann Thorac Surg. 2001;72(1): 272–4.

• But a recent meta-analysis of nitric oxide use for acute hypoxic respiratory failure in children and adults did not show a benefit in overall mortality.– Sokol J, Jacobs SE, Bohn D. Inhaled nitric oxide for acute hypoxic

respiratory failure in children and adults: a meta-analysis. Anesth Analg. 2003;97(4):989–98.

• The use of low-dose corticosteroids in ARDS was associated with improved mortality and morbidity outcomes without increased adverse reactions. – Tang BM, et al. Use of corticosteroids in acute lung injury and acute

respiratory distress syndrome: a systematic review and meta-analysis. Crit Care Med. 2009;37(5):1594–603.

• Lee et al. demonstrated a possible benefit of using low- dose corticosteroids in patients with ARDS after thoracotomy in a recent nonrandomized small observational study. – Lee HS, et al. Low-dose steroid therapy at an early phase of

postoperative acute respiratory distress syndrome. Ann Thorac Surg. 2005;79(2):405–10.

• The beneficial effects of the use of early low-dose steroids in ARDS are consistent with the hypothesis that fibroproliferation is an early response to lung injury, which is inhibited by early low-dose steroid therapy without disturbing operative wound healing.

• Sivelestat sodium hydrate is a selective neutrophil elastase inhibitor with low molecular weight and has been shown to improve respiratory status in cases of ARDS, sepsis, ventilator-induced lung injury, and ALI caused by various stresses in human patients and in animal models.– The use of neutrophil elastase inhibitor in the treatment of acute lung injury after

pneumonectomy. Lee et al. Journal of Cardiothoracic Surgery 2013, 8:69

• Kawahara et al. demonstrated that perioperative administration of sivelestat sodium hydrate from the day of the operation:

• Partially suppressed hypercytokinemia following surgical stress,

• Shortened the duration of postoperative systemic inflammatory response syndrome (SIRS),

• Stabilized postoperative circulatory status with earlier start of capillary refilling after postoperative dehydration,

• and improved postoperative hypoxia in patients with thoracic esophageal cancer who underwent thoracoscopic esophagectomy. – Kawahara Y, et al. Prospective randomized controlled study on the effects of perioperative administration

of a neutrophil elastase inhibitor to patients undergoing video-assisted thoracoscopic surgery for thoracic esophageal cancer. Dis Esophagus. 2010;23(4):329–39.

• Some previous reports have recommended an appropriate fluid restriction during surgery and for the first 48 h following major lung resections, especially pneumonectomy.– Zeldin RA, et al. Postpneumonectomy pulmonary edema. J Tho- rac

Cardiovasc Surg. 1984;87(3):359–65.

• Robert et al. recommended a conservative strategy of administration of maintenance fluids at 1–2 ml/ kg/h in the intra and postoperative periods and that a positive fluid balance of 1.5 l should not be exceeded, to mitigate the risk of multifactorial ARDS. – Evans RG, Naidu B. Does a conservative fluid management strategy in

the perioperative management of lung resection patients reduce the risk of acute lung injury? Interact Cardiovasc Thorac Surg. 2012;15(3):498–504.

• Intraoperative steroid administration prior to pulmonary artery ligation can prevent postpneumonectomy pulmonary edema.

• However, the suppressant effect of corticosteroids on wound healing and immune response raises concern.

• The indication and timing of administration of corticosteroids are still controversial and randomized controlled studies are needed to validate the benefit of corticosteroids in the treatment of ARDS after lung resection. – Cerfolio RJ, et al. Intraoperative solumedrol helps prevent post-

pneumonectomy pulmonary edema. Ann Thorac Surg. 2003;76(4):1029–33 discussion 1033–5.

Take Home Points• The definition of ARDS was updated with the

Berlin Task Force.• ALI/ARDS occurs after 2% to 4% of

pneumonectomies.• Patients with a perfusion fraction of greater

than 35% had a greater incidence of ARDS.• Chemotherpy related ARDS after

pneumonectomy should be considered in the differential if indicated.

Continued…

• Sivelestat sodium hydrate may have a role in prevention/treatment of ARDS, although further research is needed.

• Judicious use of perioperative IV fluids should be considered.

• Steroids should be considered in the treatment of post-pneumonectomy and chemotherapy-related ARDS.

References • Debapriya Datta, MD, Bimalin Lahiri, MD. Preoperative Evaluation of Patients Undergoing

Lung Resection Surgery. CHEST 2003; 123:2096–2103 • Bernard GR, Artigas A, Brigham KL, et al and The Consensus Committee: The American-

European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes an clinical trials coordination. Am J Crit Care Med 149:818-824, 1994.


• Lee et al. The use of neutrophil elastase inhibitor in the treatment of acute lung injury after pneumonectomy. Journal of Cardiothoracic Surgery 2013, 8:69

• Chemotherapy-Induced Late Acute Respiratory Distress Syndrome Following Right Pneumonectomy for Bronchogenic Carcinoma. Respir Care 2003;48(6):606–610.

• Risk factor analysis for postoperative acute respiratory distress syndrome and early mortality after pneumonectomy: The predictive value of preoperative lung perfusion distribution. J Thorac Cardiovasc Surg 2010;140:26-31)

• EVANGELOS BRIASOULIS, NICHOLAS PAVLIDIS. Noncardiogenic Pulmonary Edema: An Unusual and Serious Complication of Anticancer Therapy. The Oncologist, 2001;6:153-161.

• Kometani, et al. Acute respiratory distress syndrome after pulmonary resection. Gen Thorac Cardiovasc Surg (2013) 61:504–512

pneumonectomy and ards hartford hospital icu m&m joshua dill, do pgy-iii henry igid, md pgy-ii

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