INT J TUBERC LUNG DIS 18(7):879–881 Q 2014 The Union http://dx.doi.org/10.5588/ijtld.13.0752
CASE STUDY
ECMO: an alternative support for acute respiratory failure caused by tuberculosis? V. Cogliandro,* G. Lapadula,* A. Bandera,* A. Muscatello,* R. Marcolin,†‡ C. Abbruzzese,†‡ R. Rona,†‡ A. Gori* *Department of Internal Medicine, Division of Infectious Diseases, San Gerardo Hospital, and †Department of Experimental Medicine, University of Milano-Bicocca, Monza, ‡Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy SUMMARY
Late diagnosis of tuberculosis (TB) may result in the development of severe acute respiratory failure. High mortality rates with conventional ventilation have been reported. Extracorporeal membrane oxygenation (ECMO) may represent an effective alternative treatment.
We report a case of complicated pulmonary TB in a man who successfully underwent 3 months of ECMO. K E Y W O R D S : pulmonary tuberculosis; acute respiratory failure; extracorporeal membrane oxygenation
LATE TUBERCULOSIS (TB) diagnosis represents a significant problem in TB management. Development of acute respiratory failure (ARF) is one of the most severe complications that can occur in association with diagnostic delay.1,2 ARF is associated with a high mortality rate due to its frequent non-response to mechanical ventilation.3,4 Extracorporeal membrane oxygenation (ECMO) proved successful in recent ARF cases caused by the 2009 H1N1 influenza A pandemic who were unresponsive to conventional ventilation.5 ECMO may also represent an effective alternative strategy in treating TB-related ARF. We report a case of a severe pulmonary TB, complicated by ARF, in a man who successfully underwent prolonged ECMO support (89 days) after mechanical ventilation showed no effect.
24 mmHg). Human immunodeficiency virus serology was negative. He was immediately started on standard anti-tuberculosis treatment with rifampicin (RMP) 600 mg and isoniazid (INH) 300 mg once daily, and ethambutol 500 mg and pyrazinamide 500 three times daily. Despite oxygen therapy, further deterioration of his clinical and respiratory status (oxygen saturation level 84% in oxygen therapy with 14 l/min in reservoir 99%, heart rate 160 beats/min) was observed from the second day. The patient was transferred to the intensive care unit (ICU), where he quickly developed severe hypercapnic hypoxia (PaO2/ FiO2 [fraction of inspired oxygen] 57 mmHg, PaCO2 60 mmHg, pH 7.27) unresponsive to ventilation support and rescue therapies (inhaled nitric oxide and body pronation). Chest computed tomography (CT) scan showed bilateral pneumonia with almost complete involvement of the right lobe and the presence of other cavitating lesions in the upper right lobe (Figure C and D). Cultures of both bronchial aspirate and bronchoalveolar lavage confirmed the isolation of a Mycobacterium tuberculosis strain, which on polymerase chain reaction testing was found to be RMP- and INH-susceptible. Despite effective anti-tuberculosis treatment, the patient’s respiratory functions continued to worsen over the following days and, as a result of the failure of conventional ventilation, the patient was transferred to our ICU specialised in the use of ECMO, specifically during acute respiratory distress syndrome (ARDS) (on average 12 patients per year are treated using ECMO here). The patient under-
CASE REPORT A 20-year-old Filipino male who had lived in Italy for 6 years was hospitalised at San Gerardo Hospital after 20 kg weight loss in the previous 3 months, dry cough, fever and fatigue in the last 4 weeks and haemoptysis in the last 2 weeks. Chest X-ray showed a cavitating lesion with irregular borders in the left upper lobe and infiltrations in the right lower and medium lobe (Figure A and B). Direct microscopy of the bronchial aspirate was positive for acid-fast bacilli (AFB). The patient was febrile and tachypnoic (partial pressure of arterial oxygen [PaO2] 65 mmHg, partial pressure of arterial carbon dioxide [PaCO2]
Correspondence to: Viola Cogliandro, Division of Infectious Diseases, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy. Tel. (þ39) 039 233 9310 – 9313. Fax: (þ39) 039 233 9327. e-mail: [email protected] Article submitted 12 October 2013. Final version accepted 5 March 2014.
880
The International Journal of Tuberculosis and Lung Disease
Figure Radiological features of TB-related acute respiratory failure. A) and B) CXR and CT scan performed before ECMO, showing the pathological lesions at TB onset. Severe bilateral pneumonia involvement with multiple cavitations in the upper left lobe, infiltrate and multiple cystic areas occupying the medium and lower right lobes. C) and D) CXR and CT scan performed after 1 month of ECMO as a result of worsening pulmonary function. Despite initial improvement, pulmonary infiltrates persist. E) and F) CXR and CT scan performed after interruption of ECMO. In comparison with the previous images, radiological features show reduction in the left apex cavitation and resolution of the right lobe infiltrates. TB ¼ tuberculosis; CXR ¼ chest X-ray; CT ¼ computed tomography; ECMO ¼ extracorporeal membrane oxygenation.
went veno-venous ECMO with femoral access (blood flow 3l/min, gas flow 7l/min pure oxygen; ventilator setting: respiratory rate [RR] 12 breaths/min, tidal volume [VT] 2.6 ml/kg, end inspiratory plateau pressure [Pplat] 30 cm H2O); positive end-expiratory pressure (PEEP) was initially increased from 15 to 20 cm H2O to maintain airway pressure (Paw) at preECMO level (23 cm H2O). After a month of ECMO, the patient’s respiratory functions had not improved; due to the onset of small pneumothoraces as a consequence of high airway pressure, ECMO support was increased to provide satisfactory oxygenation (blood flow 4.1 l/min; gas flow 10 l/min) and ventilatory support was gradually reduced (RR 5 breaths/min; VT 1.9 ml/kg; Pplat 15 cm H2O; PEEP 0 cm H2O, Paw 3 cm H2O). Culture of bronchial aspirate remained positive. In the second month of ECMO, progressive improvement in respiratory function was observed, which led to gradual pulmonary weaning using neurally adjusted ventilatory assistance (from day 54) and continuous positive airway pressure (cPAP) ventilation until spontaneous breathing with oxygen 5 l/min was attained. ECMO was stopped on day 89. During these 3 months, three episodes of severe bleeding (from the urethra and the right deep femoral artery) were observed as ECMO-related complications. As regards the development of nosocomial infections, four episodes of blood stream infection
(BSI), two of urinary tract infection (UTI) and two of lower respiratory infection (LRI) occurred. The pathogens isolated from bronchial aspirate during the LRI were Candida parapsilosis and Acinetobacter baumannii; however, these were not associated with worsening pulmonary status. Three of the four BSIs were vascular catheter-related and were due to coagulase-negative staphylococcus (Staphylococcus epidermidis) and Enterococcus faecium; the other was caused by C. parapsilosis, which was also responsible for the two UTIs. The first AFB-negative bronchial aspirate cultures were obtained 2 weeks after day 104 from initiation of anti-tuberculosis treatment. The patient was transferred for re-education after 114 days of ICU hospitalisation without ventilatory support. The last chest CT scan showed improvement in the apex lesions, reduction in the cavitating lesions and bilateral consolidation of the lungs (Figure E and F).
DISCUSSION ARF is an infrequent but serious complication of pulmonary TB.1,2,6 Although TB cases requiring ICU represent only 1–3% of all hospital admissions for TB, in-hospital TB mortality rates associated with mechanical ventilation are higher (range 25.9–81%) than for other infections.1,3,4 A Canadian study comparing mortality rates among pneumonia pa-
ECMO in complicated TB
tients requiring mechanical ventilation reported significantly higher rates for pulmonary TB cases (69%, 9/13 patients) than for other different types of pneumonia (36%, 34/94 patients).1 Given its high mortality rate, an alternative treatment for TB-related ARF non-responsive to conventional ventilation is required. As confirmed by our experience, ECMO may provide effective support, particularly in patients with very severe lung injury. Experience and interest in ECMO increased during the 2009 H1N1 influenza A pandemic, when several ARDS cases were successfully treated using ECMO and survival rates were approximately twice those of patients treated with mechanical ventilation.5 During severe TB-related ARDS, the adoption of ECMO is currently very limited, and reports are described in only a few paediatric cases.7 However, our experience suggests that ECMO could also be used safely and effectively in adult pulmonary TB patients. Another innovative aspect of our case is the duration of ECMO. The circuit should be discontinued as soon as pulmonary function improves, which usually occurs after 10 days of initiating ECMO.8 Cases of patients successfully treated for longer periods have been reported, but the long-term use of ECMO, as in our case,9 is uncommon due to the higher risk of complications.10 In our case, the episodes of bleeding and the nosocomial infections did not worsen the haemodynamic stability and respiratory functions of the patient, and these did not affect the duration of ECMO. In conclusion, in our experience, complications of pulmonary TB can be successfully treated with ECMO. Its use should be encouraged as an alternative method of support when conventional ventilation fails. Moreover, ECMO should not be considered
881
only as rescue therapy for short periods; in pulmonary TB cases that require longer treatment, it can be safely prolonged until full recovery of respiratory function. Conflict of interest: none declared.
References 1 Penner C, Roberts D, Kunimoto D, Manfreda J, Long R. Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation. Am J Respir Crit Care Med 1995; 151: 867-872. 2 Sacks L V, Pendle S. Factors related to in-hospital deaths in patients with tuberculosis. Arch Intern Med 1998; 158: 19161922. 3 Kim Y J, Pack K M, Jeong E, et al. Pulmonary tuberculosis with acute respiratory failure. Eur Respir J 2008; 32: 1625-1630. 4 Lee P L, Jerng J S, Chang Y L, et al. Patient mortality of active pulmonary tuberculosis requiring mechanical ventilation. Eur Respir J 2003; 22: 141-147. 5 Noah M A, Peek G J, Finney S J, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1). JAMA 2011; 306: 1659-1668. 6 Tattevin P, Che D, Fraisse P, et al. Factors associated with patient and health care system delay in the diagnosis of tuberculosis in France. Int J Tuberc Lung Dis 2012; 16: 510515. 7 Petrillo T M, Heard M L, Fortenberry J D, Stockwell J A, Leonard M K, Jr. Respiratory failure caused by tuberculous pneumonia requiring extracorporeal membrane oxygenation. Perfusion 2001; 16: 525-529. 8 Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med 2011; 365: 1905-1914. 9 Wang C H, Chou C C, Ko W J, Lee Y C. Rescue a drowning patient by prolonged extracorporeal membrane oxygenation support for 117 days. Am J Emerg Med 2010; 28: 750.e5-7. 10 Burket J S, Bartlett R H, Vander Hyde K, Chenoweth C E. Nosocomial infections in adult patients undergoing extracorporeal membrane oxygenation. Clin Infect Dis 1999; 28: 828833.
ECMO in complicated TB
i
RESUME
Un diagnostic tardif de tuberculose (TB) risque d’aboutir a` une d´efaillance respiratoire aigue ¨ grave. On rapporte des taux de mortalit´e e´ lev´es avec la ventilation conventionnelle. L’oxyg e´ nation par membrane
extracorporelle (ECMO) pourrait eˆ tre un traitement alternatif efficace. Nous rapportons un cas de TB pulmonaire compliqu´ee chez un homme qui a b´en´efici´e avec succ`es de 3 mois d’ECMO. RESUMEN
El diagnostico ´ tard´ıo de la tuberculosis (TB) puede tener como consecuencia la aparici on ´ de insuficiencia respiratoria aguda grave. Se notifican altas tasas de mortalidad en el contexto de la ventilacion ´ cla´sica. La circulacion ´ extracorporea ´ con oxigenador de membrana
(ECMO) podr´ıa representar otra opcion ´ eficaz de tratamiento. En el presente art´ıculo se presenta un caso de TB pulmonar complicada, en un hombre cuyo desenlace fue favorable despu´es de 3 meses de ECMO.
CASE STUDY
ECMO: an alternative support for acute respiratory failure caused by tuberculosis? V. Cogliandro,* G. Lapadula,* A. Bandera,* A. Muscatello,* R. Marcolin,†‡ C. Abbruzzese,†‡ R. Rona,†‡ A. Gori* *Department of Internal Medicine, Division of Infectious Diseases, San Gerardo Hospital, and †Department of Experimental Medicine, University of Milano-Bicocca, Monza, ‡Department of Perioperative Medicine and Intensive Care, San Gerardo Hospital, Monza, Italy SUMMARY
Late diagnosis of tuberculosis (TB) may result in the development of severe acute respiratory failure. High mortality rates with conventional ventilation have been reported. Extracorporeal membrane oxygenation (ECMO) may represent an effective alternative treatment.
We report a case of complicated pulmonary TB in a man who successfully underwent 3 months of ECMO. K E Y W O R D S : pulmonary tuberculosis; acute respiratory failure; extracorporeal membrane oxygenation
LATE TUBERCULOSIS (TB) diagnosis represents a significant problem in TB management. Development of acute respiratory failure (ARF) is one of the most severe complications that can occur in association with diagnostic delay.1,2 ARF is associated with a high mortality rate due to its frequent non-response to mechanical ventilation.3,4 Extracorporeal membrane oxygenation (ECMO) proved successful in recent ARF cases caused by the 2009 H1N1 influenza A pandemic who were unresponsive to conventional ventilation.5 ECMO may also represent an effective alternative strategy in treating TB-related ARF. We report a case of a severe pulmonary TB, complicated by ARF, in a man who successfully underwent prolonged ECMO support (89 days) after mechanical ventilation showed no effect.
24 mmHg). Human immunodeficiency virus serology was negative. He was immediately started on standard anti-tuberculosis treatment with rifampicin (RMP) 600 mg and isoniazid (INH) 300 mg once daily, and ethambutol 500 mg and pyrazinamide 500 three times daily. Despite oxygen therapy, further deterioration of his clinical and respiratory status (oxygen saturation level 84% in oxygen therapy with 14 l/min in reservoir 99%, heart rate 160 beats/min) was observed from the second day. The patient was transferred to the intensive care unit (ICU), where he quickly developed severe hypercapnic hypoxia (PaO2/ FiO2 [fraction of inspired oxygen] 57 mmHg, PaCO2 60 mmHg, pH 7.27) unresponsive to ventilation support and rescue therapies (inhaled nitric oxide and body pronation). Chest computed tomography (CT) scan showed bilateral pneumonia with almost complete involvement of the right lobe and the presence of other cavitating lesions in the upper right lobe (Figure C and D). Cultures of both bronchial aspirate and bronchoalveolar lavage confirmed the isolation of a Mycobacterium tuberculosis strain, which on polymerase chain reaction testing was found to be RMP- and INH-susceptible. Despite effective anti-tuberculosis treatment, the patient’s respiratory functions continued to worsen over the following days and, as a result of the failure of conventional ventilation, the patient was transferred to our ICU specialised in the use of ECMO, specifically during acute respiratory distress syndrome (ARDS) (on average 12 patients per year are treated using ECMO here). The patient under-
CASE REPORT A 20-year-old Filipino male who had lived in Italy for 6 years was hospitalised at San Gerardo Hospital after 20 kg weight loss in the previous 3 months, dry cough, fever and fatigue in the last 4 weeks and haemoptysis in the last 2 weeks. Chest X-ray showed a cavitating lesion with irregular borders in the left upper lobe and infiltrations in the right lower and medium lobe (Figure A and B). Direct microscopy of the bronchial aspirate was positive for acid-fast bacilli (AFB). The patient was febrile and tachypnoic (partial pressure of arterial oxygen [PaO2] 65 mmHg, partial pressure of arterial carbon dioxide [PaCO2]
Correspondence to: Viola Cogliandro, Division of Infectious Diseases, San Gerardo Hospital, Via Pergolesi 33, 20900 Monza, Italy. Tel. (þ39) 039 233 9310 – 9313. Fax: (þ39) 039 233 9327. e-mail: [email protected] Article submitted 12 October 2013. Final version accepted 5 March 2014.
880
The International Journal of Tuberculosis and Lung Disease
Figure Radiological features of TB-related acute respiratory failure. A) and B) CXR and CT scan performed before ECMO, showing the pathological lesions at TB onset. Severe bilateral pneumonia involvement with multiple cavitations in the upper left lobe, infiltrate and multiple cystic areas occupying the medium and lower right lobes. C) and D) CXR and CT scan performed after 1 month of ECMO as a result of worsening pulmonary function. Despite initial improvement, pulmonary infiltrates persist. E) and F) CXR and CT scan performed after interruption of ECMO. In comparison with the previous images, radiological features show reduction in the left apex cavitation and resolution of the right lobe infiltrates. TB ¼ tuberculosis; CXR ¼ chest X-ray; CT ¼ computed tomography; ECMO ¼ extracorporeal membrane oxygenation.
went veno-venous ECMO with femoral access (blood flow 3l/min, gas flow 7l/min pure oxygen; ventilator setting: respiratory rate [RR] 12 breaths/min, tidal volume [VT] 2.6 ml/kg, end inspiratory plateau pressure [Pplat] 30 cm H2O); positive end-expiratory pressure (PEEP) was initially increased from 15 to 20 cm H2O to maintain airway pressure (Paw) at preECMO level (23 cm H2O). After a month of ECMO, the patient’s respiratory functions had not improved; due to the onset of small pneumothoraces as a consequence of high airway pressure, ECMO support was increased to provide satisfactory oxygenation (blood flow 4.1 l/min; gas flow 10 l/min) and ventilatory support was gradually reduced (RR 5 breaths/min; VT 1.9 ml/kg; Pplat 15 cm H2O; PEEP 0 cm H2O, Paw 3 cm H2O). Culture of bronchial aspirate remained positive. In the second month of ECMO, progressive improvement in respiratory function was observed, which led to gradual pulmonary weaning using neurally adjusted ventilatory assistance (from day 54) and continuous positive airway pressure (cPAP) ventilation until spontaneous breathing with oxygen 5 l/min was attained. ECMO was stopped on day 89. During these 3 months, three episodes of severe bleeding (from the urethra and the right deep femoral artery) were observed as ECMO-related complications. As regards the development of nosocomial infections, four episodes of blood stream infection
(BSI), two of urinary tract infection (UTI) and two of lower respiratory infection (LRI) occurred. The pathogens isolated from bronchial aspirate during the LRI were Candida parapsilosis and Acinetobacter baumannii; however, these were not associated with worsening pulmonary status. Three of the four BSIs were vascular catheter-related and were due to coagulase-negative staphylococcus (Staphylococcus epidermidis) and Enterococcus faecium; the other was caused by C. parapsilosis, which was also responsible for the two UTIs. The first AFB-negative bronchial aspirate cultures were obtained 2 weeks after day 104 from initiation of anti-tuberculosis treatment. The patient was transferred for re-education after 114 days of ICU hospitalisation without ventilatory support. The last chest CT scan showed improvement in the apex lesions, reduction in the cavitating lesions and bilateral consolidation of the lungs (Figure E and F).
DISCUSSION ARF is an infrequent but serious complication of pulmonary TB.1,2,6 Although TB cases requiring ICU represent only 1–3% of all hospital admissions for TB, in-hospital TB mortality rates associated with mechanical ventilation are higher (range 25.9–81%) than for other infections.1,3,4 A Canadian study comparing mortality rates among pneumonia pa-
ECMO in complicated TB
tients requiring mechanical ventilation reported significantly higher rates for pulmonary TB cases (69%, 9/13 patients) than for other different types of pneumonia (36%, 34/94 patients).1 Given its high mortality rate, an alternative treatment for TB-related ARF non-responsive to conventional ventilation is required. As confirmed by our experience, ECMO may provide effective support, particularly in patients with very severe lung injury. Experience and interest in ECMO increased during the 2009 H1N1 influenza A pandemic, when several ARDS cases were successfully treated using ECMO and survival rates were approximately twice those of patients treated with mechanical ventilation.5 During severe TB-related ARDS, the adoption of ECMO is currently very limited, and reports are described in only a few paediatric cases.7 However, our experience suggests that ECMO could also be used safely and effectively in adult pulmonary TB patients. Another innovative aspect of our case is the duration of ECMO. The circuit should be discontinued as soon as pulmonary function improves, which usually occurs after 10 days of initiating ECMO.8 Cases of patients successfully treated for longer periods have been reported, but the long-term use of ECMO, as in our case,9 is uncommon due to the higher risk of complications.10 In our case, the episodes of bleeding and the nosocomial infections did not worsen the haemodynamic stability and respiratory functions of the patient, and these did not affect the duration of ECMO. In conclusion, in our experience, complications of pulmonary TB can be successfully treated with ECMO. Its use should be encouraged as an alternative method of support when conventional ventilation fails. Moreover, ECMO should not be considered
881
only as rescue therapy for short periods; in pulmonary TB cases that require longer treatment, it can be safely prolonged until full recovery of respiratory function. Conflict of interest: none declared.
References 1 Penner C, Roberts D, Kunimoto D, Manfreda J, Long R. Tuberculosis as a primary cause of respiratory failure requiring mechanical ventilation. Am J Respir Crit Care Med 1995; 151: 867-872. 2 Sacks L V, Pendle S. Factors related to in-hospital deaths in patients with tuberculosis. Arch Intern Med 1998; 158: 19161922. 3 Kim Y J, Pack K M, Jeong E, et al. Pulmonary tuberculosis with acute respiratory failure. Eur Respir J 2008; 32: 1625-1630. 4 Lee P L, Jerng J S, Chang Y L, et al. Patient mortality of active pulmonary tuberculosis requiring mechanical ventilation. Eur Respir J 2003; 22: 141-147. 5 Noah M A, Peek G J, Finney S J, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1). JAMA 2011; 306: 1659-1668. 6 Tattevin P, Che D, Fraisse P, et al. Factors associated with patient and health care system delay in the diagnosis of tuberculosis in France. Int J Tuberc Lung Dis 2012; 16: 510515. 7 Petrillo T M, Heard M L, Fortenberry J D, Stockwell J A, Leonard M K, Jr. Respiratory failure caused by tuberculous pneumonia requiring extracorporeal membrane oxygenation. Perfusion 2001; 16: 525-529. 8 Brodie D, Bacchetta M. Extracorporeal membrane oxygenation for ARDS in adults. N Engl J Med 2011; 365: 1905-1914. 9 Wang C H, Chou C C, Ko W J, Lee Y C. Rescue a drowning patient by prolonged extracorporeal membrane oxygenation support for 117 days. Am J Emerg Med 2010; 28: 750.e5-7. 10 Burket J S, Bartlett R H, Vander Hyde K, Chenoweth C E. Nosocomial infections in adult patients undergoing extracorporeal membrane oxygenation. Clin Infect Dis 1999; 28: 828833.
ECMO in complicated TB
i
RESUME
Un diagnostic tardif de tuberculose (TB) risque d’aboutir a` une d´efaillance respiratoire aigue ¨ grave. On rapporte des taux de mortalit´e e´ lev´es avec la ventilation conventionnelle. L’oxyg e´ nation par membrane
extracorporelle (ECMO) pourrait eˆ tre un traitement alternatif efficace. Nous rapportons un cas de TB pulmonaire compliqu´ee chez un homme qui a b´en´efici´e avec succ`es de 3 mois d’ECMO. RESUMEN
El diagnostico ´ tard´ıo de la tuberculosis (TB) puede tener como consecuencia la aparici on ´ de insuficiencia respiratoria aguda grave. Se notifican altas tasas de mortalidad en el contexto de la ventilacion ´ cla´sica. La circulacion ´ extracorporea ´ con oxigenador de membrana
(ECMO) podr´ıa representar otra opcion ´ eficaz de tratamiento. En el presente art´ıculo se presenta un caso de TB pulmonar complicada, en un hombre cuyo desenlace fue favorable despu´es de 3 meses de ECMO.
