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Sepsis and Neurologic Deficit After Lung Transplantation
pulmonary and critical care pearls Sepsis and Neurologic Deficit After Lung Transplantation* Thomas J. Gross, MD, FCCP; and Paul J. Christensen, MD
(CHEST 2000; 118:849 – 851)
A
54-year-old woman underwent an orthotopic left lung transplant for the treatment of end-stage emphysema related to chronic cigarette smoking. She was extubated on the second postoperative day and discharged from the hospital 3 weeks after transplantation without complications. She returned from the regional transplant center to her rural Iowa home 6 weeks after surgery and did well without supplemental oxygen and without limiting dyspnea. Her medications included the following: prednisone, 15 mg/d; tacrolimus, 2 mg every morning and 3 mg at night; azathiaprine, 125 mg/d; acyclovir, 400 mg tid; itraconazole, 400 mg/d; trimethoprim/sulfamethoxazole, 3 days/wk; ranitidine, 150 mg at bedtime for long-standing reflux disease; use of a combination albuterol/ipatropium bromide metered-dose inhaler qid; and postmenopausal hormone replacements. One week after arriving home, she noted the onset of fever, small joint arthralgias, and left hand pain; and she was admitted to the hospital. Admission blood cultures grew Pseudomonas aeruginosa. Despite IV antibiotics, she developed persistent fevers, hypotension, and respiratory distress prompting transfer to the medical ICU and treatment with IV pressors and mechanical ventilation. Physical Examination Examination revealed an anxious woman receiving mechanical ventilation. Her temperature was 38.5°C; BP systolic, about 90 mm Hg, with the patient receiving dopamine, 5 g/kg/min; pulse, sinus tachycardia at 120 beats/min; and minute ventilation, 12 L/min on assist/control ventilation with tidal volume of 600 mL. She answered questions
*From the Division of Pulmonary, Critical Care, and Occupational Medicine (Dr. Gross), University of Iowa Health Care, Iowa City, IA; and the Division of Pulmonary and Critical Care (Dr. Christensen), University of Michigan, Ann Arbor, MI. Manuscript received September 16, 1999; revision accepted December 9, 1999. Correspondence to: Thomas J. Gross, MD, FCCP, Division of Pulmonary, Critical Care, and Occupational Medicine, Room C33 GH, The University of Iowa Hospitals & Clinics, Iowa City, IA 52242; e-mail: [email protected]
appropriately and had no localizing complaints. She had no rashes or skin lesions. Her thoracotomy scar was healed and nontender. She had distant breath sounds with rhonchi in her native right lung; the left lung examination was normal. Cardiac examination revealed no murmurs. Her abdomen was soft and without organomegaly. She had no edema and her peripheral pulses were full. Laboratory Findings Laboratory studies showed a hemoglobin of 8 mg/dL with a hematocrit of 24%. The peripheral smear demonstrated scattered schistocytes. The leukocyte count was mildly elevated (11 ⫻ 103/L) with immature granulocytes. The platelet count was low (90 ⫻ 103/L). Electrolytes and liver enzymes were normal except for an elevated lactate dehydrogenase of 400 U (100 to 200 U/L normal range). The serum creatinine was elevated at 3.9 mg/dL, urinalysis revealed hematuria without casts, and the patient was oliguric on pressors. Prothrombin and partial thromboplastin times were normal. Chest radiograph revealed a hyperinflated native lung and normal transplant with a small left pleural effusion. Chest CT scan revealed no infiltrates in the transplanted lung, emphysema in the native lung, and a small left pleural effusion. Ultrasound-guided thoracentesis yielded serosanguinous fluid with a pH of 7.42, glucose of 145 mg/dL (plasma, 180 mg/dL), total protein of 1.8 g/dL (plasma, 6.4 g/dL), lactate dehydrogenase of 267 U/L (plasma, 400 U/L), and a cell count showing 900 leukocytes/L with 80% neutrophils. A transthoracic echocardiogram (TTE) revealed normal left-sided chamber size and function. There was mild right ventricular dilatation. All valves were seen and appeared normal without vegetation. The pleural fluid quickly grew Gram-negative rods, and a chest tube was placed. The next day, the patient became confused and hemiparetic. An emergent MRI study of the head showed multiple lesions consistent with infarctions. What is the imaging study of choice to make this diagnosis? CHEST / 118 / 3 / SEPTEMBER, 2000
849
Answer: Transesophageal echocardiography Diagnosis: Septic pulmonary venous thromboembolism. Lung transplantation is increasingly used to treat patients with terminal lung diseases. Although technical and postoperative medical care continues to improve outcome, transplant patients remain susceptible to a long list of serious complications. Most of these are related to organ rejection and the sequelae of intensive immunosuppression. However, unique technical difficulties can complicate the requisite anatomic connections. Airway anastomoses are prone to stenosis and dehiscence in the early postoperative period. Vascular complications following lung transplantation are relatively uncommon but are associated with a high morbidity and mortality. Pulmonary venous complications usually present in the early postoperative period with unilateral pulmonary edema and respiratory failure. This can be due to anastomotic stenosis and/or thrombosis. However, even in the absence of symptoms, pulmonary venous occlusions can be detected in up to 30% of lung transplant recipients studied by transesophageal echocardiography (TEE) within 30 days of operation. Echocardiography study of asymptomatic single lung transplant recipients frequently reveals measurable increases in resistance across the pulmonary venous anastomoses with increased flow velocity and preanastomotic venous dilation. Such alterations in blood flow and shear force at the left atrial anastomotic site may predispose to endothelial injury and promote local thrombogenesis. Occasional patients may present up to 2 years after transplant with unilateral pulmonary edema due to pulmonary venous obstruction. Thus, pulmonary venous occlusion may present early or late in the postoperative period. While symptoms of unilateral vascular congestion and respiratory failure may prompt investigations of
vascular patency, posttransplant venous thrombosis may also present as embolic stroke. In such cases, sudden neurologic deterioration and focal abnormalities on physical examination and imaging studies should lead to suspicion of a cardiac embolic source. No abnormalities are usually seen with TTE, but TEE typically reveals venous endoluminal clot. The optimal treatment of pulmonary venous thrombosis after lung transplant remains unclear. Because symptomatic pulmonary venous occlusion is associated with an increased early postoperative mortality, anticoagulation seems warranted for documented thrombi. Lung transplant patients, however, are at high risk for perioperative intrathoracic bleeding, and anticoagulation further increases this risk. Systemic fibrinolytic therapy has also been successfully used to treat a symptomatic occlusive pulmonary venous thrombus. Some centers have approached symptomatic pulmonary venous occlusion with emergent surgical thrombectomy, which is associated with a high perioperative mortality. Small thrombi detected by TEE have been observed to resolve without specific intervention. These clots were associated with only mildly increased venous flow velocity, suggesting that preserved venous flow may increase the likelihood of spontaneous dissolution. Thus, venous occlusion after lung transplantation appears to be often clinically silent yet associated with an increased mortality. Specific treatment and/or prophylaxis guidelines will require larger cross-sectional studies of the incidence and response to therapy of pulmonary venous thrombosis after transplant. Our patient presented with bacteremia and a systemic symptom complex suggestive of left-sided endocarditis (embolic stroke, fever, bacteremia, arthralgias, hematuria, hemolysis). TTE was unrevealing, but TEE clearly demonstrated a venous thrombus (Fig 1). The cardiac valves were normal without vegetations and the interatrial septum was mobile
Figure 1. Sequential TEE images demonstrate a mobile thrombus (arrowhead) emanating from the left superior pulmonary vein (PV) where it joins the left atrium (LA) at the juncture of the LA appendage (LAA). 850
Pulmonary and Critical Care Pearls
without evidence of a shunt on a “bubble contrast” examination. We believe this patient represents the first description of septic pulmonary venous thrombophlebitis complicating unilateral lung transplantation. Unfortunately, despite anticoagulation, our patient did not recover neurologically and died several weeks later. Clinical Pearls 1. Pulmonary venous thrombosis frequently presents with unilateral pulmonary edema and respiratory failure in the early posttransplant period. However, a symptom complex suggestive of cardiac emboli (embolic stoke, left-sided endocarditis) in the lung transplant patient should prompt investigation for pulmonary venous thromboemboli originating from the left atrial anastomosis. 2. TEE is the imaging modality of choice for evaluating the left atrial-pulmonary vein interface after lung transplant. 3. Symptomatic pulmonary venous thromboembolism is associated with an increased mortality and appears best treated with routine anticoagulation when feasible. A clot that only partially obstructs venous flow may resolve spontaneously.
Suggested Readings Clark SC, Levine AJ, Hasan A, et al. Vascular complications of lung transplantation. Ann Thorac Surg 1996; 61:1079 –1082 Leibowitz DW, Smith CR, Michler RE, et al. Incidence of pulmonary vein complications after lung transplantation: a prospective transesophageal echocardiography study. J Am Coll Cardiol 1994; 24:671– 675 Liguori C, Schulman L, Weslow R, et al. Late pulmonary venous complications after lung transplantation. J Am Soc Echocardiogr 1997; 10:763–767 Michel-Cherqui M, Brusset A, Liu N, et al. Intraoperative transesophageal echocardiographic assessment of vascular anastomoses in lung transplantation. Chest 1997; 111:1229 –1235 Nahar T, Savoia MT, Liguori C, et. al. Spontaneous resolution of pulmonary venous thrombosis after lung transplantation. J Am Soc Echocardiogr 1998; 11:209 –212 Reilly MP, Plappert TJ, Wiegers SE. Cerebrovascular emboli related to pulmonary venous thrombosis after lung transplantation. J Am Soc Echocardiogr 1998; 11:299 –302 Ross DJ, Vassolo M, Kass R, et al. Transesophageal echocardiographic assessment of pulmonary venous flow after single lung transplantation. J Heart Lung Transplant 1993; 12:689 – 694 Schmid C, Gulba DC, Heublein B, et al. Systemic recombinant tissue plasminogen activator lysis for left atrial thrombus formation after single lung transplantation. Ann Thorac Surg 1992; 53:338 –340 Shah A, Michler RE, Downey RJ, et al. Management strategies for pulmonary vein thrombosis following single lung transplant. J Cardiovasc Surg 1995; 10:101–110 Stang MR, Hinderliter AL, Gott KK, et al. Atrial anastomotic thrombus causes neurologic deficits in a lung transplant recipient. Transplantation 1996; 62:693– 695
CHEST / 118 / 3 / SEPTEMBER, 2000
851
(CHEST 2000; 118:849 – 851)
A
54-year-old woman underwent an orthotopic left lung transplant for the treatment of end-stage emphysema related to chronic cigarette smoking. She was extubated on the second postoperative day and discharged from the hospital 3 weeks after transplantation without complications. She returned from the regional transplant center to her rural Iowa home 6 weeks after surgery and did well without supplemental oxygen and without limiting dyspnea. Her medications included the following: prednisone, 15 mg/d; tacrolimus, 2 mg every morning and 3 mg at night; azathiaprine, 125 mg/d; acyclovir, 400 mg tid; itraconazole, 400 mg/d; trimethoprim/sulfamethoxazole, 3 days/wk; ranitidine, 150 mg at bedtime for long-standing reflux disease; use of a combination albuterol/ipatropium bromide metered-dose inhaler qid; and postmenopausal hormone replacements. One week after arriving home, she noted the onset of fever, small joint arthralgias, and left hand pain; and she was admitted to the hospital. Admission blood cultures grew Pseudomonas aeruginosa. Despite IV antibiotics, she developed persistent fevers, hypotension, and respiratory distress prompting transfer to the medical ICU and treatment with IV pressors and mechanical ventilation. Physical Examination Examination revealed an anxious woman receiving mechanical ventilation. Her temperature was 38.5°C; BP systolic, about 90 mm Hg, with the patient receiving dopamine, 5 g/kg/min; pulse, sinus tachycardia at 120 beats/min; and minute ventilation, 12 L/min on assist/control ventilation with tidal volume of 600 mL. She answered questions
*From the Division of Pulmonary, Critical Care, and Occupational Medicine (Dr. Gross), University of Iowa Health Care, Iowa City, IA; and the Division of Pulmonary and Critical Care (Dr. Christensen), University of Michigan, Ann Arbor, MI. Manuscript received September 16, 1999; revision accepted December 9, 1999. Correspondence to: Thomas J. Gross, MD, FCCP, Division of Pulmonary, Critical Care, and Occupational Medicine, Room C33 GH, The University of Iowa Hospitals & Clinics, Iowa City, IA 52242; e-mail: [email protected]
appropriately and had no localizing complaints. She had no rashes or skin lesions. Her thoracotomy scar was healed and nontender. She had distant breath sounds with rhonchi in her native right lung; the left lung examination was normal. Cardiac examination revealed no murmurs. Her abdomen was soft and without organomegaly. She had no edema and her peripheral pulses were full. Laboratory Findings Laboratory studies showed a hemoglobin of 8 mg/dL with a hematocrit of 24%. The peripheral smear demonstrated scattered schistocytes. The leukocyte count was mildly elevated (11 ⫻ 103/L) with immature granulocytes. The platelet count was low (90 ⫻ 103/L). Electrolytes and liver enzymes were normal except for an elevated lactate dehydrogenase of 400 U (100 to 200 U/L normal range). The serum creatinine was elevated at 3.9 mg/dL, urinalysis revealed hematuria without casts, and the patient was oliguric on pressors. Prothrombin and partial thromboplastin times were normal. Chest radiograph revealed a hyperinflated native lung and normal transplant with a small left pleural effusion. Chest CT scan revealed no infiltrates in the transplanted lung, emphysema in the native lung, and a small left pleural effusion. Ultrasound-guided thoracentesis yielded serosanguinous fluid with a pH of 7.42, glucose of 145 mg/dL (plasma, 180 mg/dL), total protein of 1.8 g/dL (plasma, 6.4 g/dL), lactate dehydrogenase of 267 U/L (plasma, 400 U/L), and a cell count showing 900 leukocytes/L with 80% neutrophils. A transthoracic echocardiogram (TTE) revealed normal left-sided chamber size and function. There was mild right ventricular dilatation. All valves were seen and appeared normal without vegetation. The pleural fluid quickly grew Gram-negative rods, and a chest tube was placed. The next day, the patient became confused and hemiparetic. An emergent MRI study of the head showed multiple lesions consistent with infarctions. What is the imaging study of choice to make this diagnosis? CHEST / 118 / 3 / SEPTEMBER, 2000
849
Answer: Transesophageal echocardiography Diagnosis: Septic pulmonary venous thromboembolism. Lung transplantation is increasingly used to treat patients with terminal lung diseases. Although technical and postoperative medical care continues to improve outcome, transplant patients remain susceptible to a long list of serious complications. Most of these are related to organ rejection and the sequelae of intensive immunosuppression. However, unique technical difficulties can complicate the requisite anatomic connections. Airway anastomoses are prone to stenosis and dehiscence in the early postoperative period. Vascular complications following lung transplantation are relatively uncommon but are associated with a high morbidity and mortality. Pulmonary venous complications usually present in the early postoperative period with unilateral pulmonary edema and respiratory failure. This can be due to anastomotic stenosis and/or thrombosis. However, even in the absence of symptoms, pulmonary venous occlusions can be detected in up to 30% of lung transplant recipients studied by transesophageal echocardiography (TEE) within 30 days of operation. Echocardiography study of asymptomatic single lung transplant recipients frequently reveals measurable increases in resistance across the pulmonary venous anastomoses with increased flow velocity and preanastomotic venous dilation. Such alterations in blood flow and shear force at the left atrial anastomotic site may predispose to endothelial injury and promote local thrombogenesis. Occasional patients may present up to 2 years after transplant with unilateral pulmonary edema due to pulmonary venous obstruction. Thus, pulmonary venous occlusion may present early or late in the postoperative period. While symptoms of unilateral vascular congestion and respiratory failure may prompt investigations of
vascular patency, posttransplant venous thrombosis may also present as embolic stroke. In such cases, sudden neurologic deterioration and focal abnormalities on physical examination and imaging studies should lead to suspicion of a cardiac embolic source. No abnormalities are usually seen with TTE, but TEE typically reveals venous endoluminal clot. The optimal treatment of pulmonary venous thrombosis after lung transplant remains unclear. Because symptomatic pulmonary venous occlusion is associated with an increased early postoperative mortality, anticoagulation seems warranted for documented thrombi. Lung transplant patients, however, are at high risk for perioperative intrathoracic bleeding, and anticoagulation further increases this risk. Systemic fibrinolytic therapy has also been successfully used to treat a symptomatic occlusive pulmonary venous thrombus. Some centers have approached symptomatic pulmonary venous occlusion with emergent surgical thrombectomy, which is associated with a high perioperative mortality. Small thrombi detected by TEE have been observed to resolve without specific intervention. These clots were associated with only mildly increased venous flow velocity, suggesting that preserved venous flow may increase the likelihood of spontaneous dissolution. Thus, venous occlusion after lung transplantation appears to be often clinically silent yet associated with an increased mortality. Specific treatment and/or prophylaxis guidelines will require larger cross-sectional studies of the incidence and response to therapy of pulmonary venous thrombosis after transplant. Our patient presented with bacteremia and a systemic symptom complex suggestive of left-sided endocarditis (embolic stroke, fever, bacteremia, arthralgias, hematuria, hemolysis). TTE was unrevealing, but TEE clearly demonstrated a venous thrombus (Fig 1). The cardiac valves were normal without vegetations and the interatrial septum was mobile
Figure 1. Sequential TEE images demonstrate a mobile thrombus (arrowhead) emanating from the left superior pulmonary vein (PV) where it joins the left atrium (LA) at the juncture of the LA appendage (LAA). 850
Pulmonary and Critical Care Pearls
without evidence of a shunt on a “bubble contrast” examination. We believe this patient represents the first description of septic pulmonary venous thrombophlebitis complicating unilateral lung transplantation. Unfortunately, despite anticoagulation, our patient did not recover neurologically and died several weeks later. Clinical Pearls 1. Pulmonary venous thrombosis frequently presents with unilateral pulmonary edema and respiratory failure in the early posttransplant period. However, a symptom complex suggestive of cardiac emboli (embolic stoke, left-sided endocarditis) in the lung transplant patient should prompt investigation for pulmonary venous thromboemboli originating from the left atrial anastomosis. 2. TEE is the imaging modality of choice for evaluating the left atrial-pulmonary vein interface after lung transplant. 3. Symptomatic pulmonary venous thromboembolism is associated with an increased mortality and appears best treated with routine anticoagulation when feasible. A clot that only partially obstructs venous flow may resolve spontaneously.
Suggested Readings Clark SC, Levine AJ, Hasan A, et al. Vascular complications of lung transplantation. Ann Thorac Surg 1996; 61:1079 –1082 Leibowitz DW, Smith CR, Michler RE, et al. Incidence of pulmonary vein complications after lung transplantation: a prospective transesophageal echocardiography study. J Am Coll Cardiol 1994; 24:671– 675 Liguori C, Schulman L, Weslow R, et al. Late pulmonary venous complications after lung transplantation. J Am Soc Echocardiogr 1997; 10:763–767 Michel-Cherqui M, Brusset A, Liu N, et al. Intraoperative transesophageal echocardiographic assessment of vascular anastomoses in lung transplantation. Chest 1997; 111:1229 –1235 Nahar T, Savoia MT, Liguori C, et. al. Spontaneous resolution of pulmonary venous thrombosis after lung transplantation. J Am Soc Echocardiogr 1998; 11:209 –212 Reilly MP, Plappert TJ, Wiegers SE. Cerebrovascular emboli related to pulmonary venous thrombosis after lung transplantation. J Am Soc Echocardiogr 1998; 11:299 –302 Ross DJ, Vassolo M, Kass R, et al. Transesophageal echocardiographic assessment of pulmonary venous flow after single lung transplantation. J Heart Lung Transplant 1993; 12:689 – 694 Schmid C, Gulba DC, Heublein B, et al. Systemic recombinant tissue plasminogen activator lysis for left atrial thrombus formation after single lung transplantation. Ann Thorac Surg 1992; 53:338 –340 Shah A, Michler RE, Downey RJ, et al. Management strategies for pulmonary vein thrombosis following single lung transplant. J Cardiovasc Surg 1995; 10:101–110 Stang MR, Hinderliter AL, Gott KK, et al. Atrial anastomotic thrombus causes neurologic deficits in a lung transplant recipient. Transplantation 1996; 62:693– 695
CHEST / 118 / 3 / SEPTEMBER, 2000
851