ASAIO Journal 2014
Case Reports
The Use of ECMO in HIV/AIDS with Pneumocystis jirovecii Pneumonia: A Case Report and Review of the Literature Kelly Cawcutt,*† Alice Gallo De Moraes,* Sarah J. Lee,* John G. Park,* Gregory J. Schears,‡ and Michael E. Nemergut ‡
There are few reports of extracorporeal membrane oxygenation (ECMO) therapy for respiratory failure because of Pneumocystis jirovecii pneumonia (PJP) in patients with acquired immunodeficiency syndrome (AIDS). None of the cases reported involvement of immune reconstitution inflammatory syndrome (IRIS), a paradoxical clinical worsening after the initiation of antiretroviral therapy (ART) in ART-naïve patients because of an exaggerated systemic inflammation with cell count recovery. We present a patient with newly diagnosed AIDS and PJP pneumonia that progressed to acute respiratory distress syndrome (ARDS) secondary to probable IRIS for which veno-venous ECMO was initiated. He transitioned to conventional ventilator after 57 days of ECMO therapy. However, he did not survive to hospital discharge. Combined with four previously reported cases of ARDS in human immunodeficiency virus patients secondary to PJP treated with ECMO, three of the five patients survived to ECMO decannulation. Extracorporeal membrane oxygenation is considered an accepted modality for adult patients with respiratory and/or cardiac failure refractory to maximal medical therapy. As ECMO becomes increasingly utilized in clinical practice, there is ongoing controversy regarding the appropriate selection of patients. In the past, contraindications to ECMO included immunocompromised states and conditions with known poor prognosis. The cases herein suggest the indications and contraindications warrant further discussion and research. ASAIO Journal 2014; 60:606–608.
in human immunodeficiency virus (HIV)-infected patients.1 In 2010, there was an estimated 47,230 new HIV/acquired immunodeficiency syndrome (AIDS) diagnosis in the United States.2 PJP accounted for 35% of cases with respiratory failure among HIV/AIDS patients admitted to the intensive care unit.2 There are a few reported cases of respiratory failure because of PJP requiring extracorporeal membrane oxygenation (ECMO) therapy. None had concurrent immune reconstitution inflammatory syndrome (IRIS). We present a case with a newly diagnosed AIDS, PJP pneumonia, and probable IRIS whose condition progressed to refractory acute respiratory distress syndrome (ARDS), for which veno-venous (VV) ECMO was required. We also review four published cases in which ECMO was used in adult AIDS patients with severe hypoxemia from PJP. Case Description A 45-year-old man presented to an outpatient clinic with fever, productive cough, and generalized weakness. He was treated empirically for community-acquired pneumonia and steadily worsened despite a 10 day course of amoxicillin-clavulanate. He was ultimately hospitalized and tested positive for HIV with CD4 count of 33 cells/ml (Figure 1). Bronchoalveolar lavage demonstrated P. jirovecii by polymerase chain reaction testing, for which he was initiated on trimethoprim/ sulfamethoxazole (TMP/SMX). He had hypoxia with an alveolar-arterial oxygen gradient of 26 but required persistent supplemental oxygen. Therefore, he was given prednisone. Efavirenz/emtricitabine/tenofovir (Atripla[AQ: Please provide
Key Words: critical care, case report, extracorporeal membrane oxygenation, acquired immunodeficiency syndrome, Pneumocystis jirovecii pneumonia, immune reconstitution inflammatory syndrome, human immunodeficiency virus
Pneumocystis jirovecii pneumonia (PJP, previously classified
as Pneumocystis carinii) is one of the leading causes of mortality
From the *Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota; †Department of Medicine, Division of Infectious Disease, Mayo Clinic, Rochester, Minnesota; and ‡Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota. Submitted for consideration April 2014; accepted for publication in revised form May 2014. Disclosure: This article was supported by the Division of Critical Care and by the Department of Anesthesiology with no direct financial support. Correspondence: Michael E. Nemergut, Department of Anesthesiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs Figure 1. Admission chest x-ray.
DOI: 10.1097/MAT.0000000000000112
606
USE OF EXTRACORPOREAL MEMBRANE OXYGENATION IN HIV/AIDS WITH PJP PNEUMONIA
manufacturer information (city, state, country if outside US) for Atripla.]) was then started for treatment of AIDS. He was discharged from the hospital after 6 days with a plan to complete a 3 week course of TMP/SMX with a prednisone taper, continue efavirenz/emtricitabine/tenofovir combined with prophylactic fluconazole and azithromycin. Approximately 1 week later, he was readmitted to the hospital with acute hypoxic respiratory failure requiring intubation and mechanical ventilation (Figure 2: chest x-ray on readmission). He was started on vancomycin, levofloxacin, piperacillintazobactam, and approximately 0.75 mg/kg of methylprednisolone IV per day. Trimethoprim/sulfamethoxazole therapy was also continued. Despite these therapies, his respiratory status deteriorated with worsening hypoxia. The Infectious Disease consult team felt he likely developed IRIS given the timing of respiratory decompensation in respect to the initiation of antiretroviral therapy (ART), demonstration of medical compliance with TMP/SMX therapy by serum drug levels, and lack of another new identified pathogen besides Pneumocystis. Thus, corticosteroid dosing was increased to approximately 1.5 mg/kg per day. Unfortunately, he developed ARDS refractory to all attempted therapies including lung-protective ventilation, prone positioning, neuromuscular blocking agents, and inhaled alprostadil. Despite these maneuvers, arterial blood gas analysis showed persistent hypoxia (PaO2 of 50 mmHg) on 100% fraction of inspired oxygen (FiO2), positive endexpiratory pressure (PEEP) of 15, resulting in PaO2 to FiO2 ratio of 50. A 31-French Avalon VV ECMO catheter was placed into the right internal jugular vein under sterile conditions in the operating room. He was subsequently initiated with circuit flow of 4 l/min and sweep of 4 l/min of oxygen (100% FiO2). The cannula exit sites were managed through the standard protocol for our institution, which includes insertion with initial chlorhexidine cleansing, use of maximal sterile barriers, suture securement, and repeat preparation of the insertion site with chlorhexidine at the end of the procedure and Tegaderm dressing. If the dressing does not become compromised, it is changed every 7 days.
Figure 2. Readmission chest x-ray.
607
Concurrent ventilator settings included a tidal volume of 300 ml, respiratory rate of 20 bpm, PEEP of 10 mmHg, and FiO2 of 80%. Resultant ABG revealed a pH of 7.27, PCO2 of 53 mmHg, PaO2 of 64 mmHg, base excess of −3, and SpO2 saturation of 88.5%. Antiretroviral therapy was discontinued the day after ECMO initiation secondary to concerns for poor absorption because of ileus and possible toxicity given his acute kidney injury but was restarted approximately 1 week later when ileus improved and never required dialysis. Extracorporeal membrane oxygenation was at maximum setting during the first week with the circuit flow at approximately 4 l/min and oxygen sweep of 11 L/min (100% FiO2), whereas on bilevel mechanical ventilation with settings of PEEPhigh of 26 mmHg, PEEPlow of 10 mmHg, PS of 10, and FiO2 of 100%. Despite high FiO2, his oxygen saturation remained in the 80–85% range on arterial blood samples for the first 10 days on ECMO. Subsequently, ECMO support was slowly weaned while he continued on his antiretroviral medications and therapy for PJP with corticosteroids, TMP/SMX, clindamycin, and primaquine. The patient’s clinical course was further complicated by the development of bilateral pneumothoraces requiring chest tube placements, intracranial hemorrhagic mass of unknown etiology, bacteremia, and critical illness myopathy. The intracranial hemorrhagic mass lesion was 1.4 × 1.2 cm in size. The heparin dose was 1700 U/hr at the time of diagnosis and was not changed in direct response to this finding. A repeat computed tomography scan of his head was completed on days 3 and 7 after the event with no evidence of increased hemorrhage around the lesion. After 57 days on ECMO, as his oxygenation improved, he was successfully decannulated. He was transferred out of the intensive care unit to a chronic ventilator unit but ultimately succumbed to multiorgan failure combined with his other comorbidities on hospital day 97. Discussion ECMO is becoming an accepted salvage therapy for respiratory and/or circulatory failure refractory to maximal medical therapy.3 Favorable outcomes in severe ARDS have been reported with ECMO use during the 2009 H1N1 influenza pandemic and in the CESAR trial, which led to increased interest and use of ECMO for refractory respiratory failure.4,5,6 As ECMO becomes increasingly utilized in clinical practice, guidelines for its use in medically complex adult patients are absent, and the literature for its use in severe refractory ARDS is limited.7 ECMO guidelines have listed major immunodeficiency states and comorbidities associated with poor outcomes as relative contraindications. Similarly, severe PJP requiring mechanical ventilation was previously thought to be medically futile. However, with the advent of new antiretroviral medications and initiatives to improve diagnostic testing and medication compliance, HIV/ AIDS can be managed as a chronic condition, particularly because these patients have similar life expectancy to the general population.8 Therefore, AIDS or PJP should not be a contraindication for the use of ECMO. In addition, numerous advances in materials and ECMO circuit design have allowed the utilization of this support technology in higher risk patients with less complications, thus the guidelines for its use need to be reconsidered.4
608 CAWCUTT et al. Table 1. Patients with Respiratory Failure Caused by Pneumocystis jirovecii Pneumonia Treated with ECMO
Age (y)/Sex
CD4 (cells/ ml)
HIV Viral Load (copies/ ml)
Timing of ART Initiation (Pre-, On-, Post-ECMO)
PaO2 (mmHg)/ FiO2 (%)
ECMO Initiation (hospital day)/ Duration (days)
1 (our patient)
45/M
33
113,000
Pre
59/60
5/57
2 (Goodman et al)11
30/F
13
976,631
Post
50.1/100
3/7
3 (Gutermann et al)12
55/M
9
80,235
Post
NR/NR
4/4
4 (Steppan)13 5 (Goodman et al)11
39/M 25/M
69 36
6297 622,234
Pre Pre
NR/100 63.6/100
12/14 18/69
Patient (Ref)
Outcome Died in hospital, after decannulation Survived to hospital discharge Survived to hospital discharge Died on ECMO Died on ECMO
ART, antiretroviral therapy; ECMO, extracorporeal membrane oxygenation; NR, not reported.
Our case was unique in that PJP and IRIS contributed to the ARDS presentation. To our knowledge, our case is the first reported use of ECMO for PJP in an AIDS patient complicated by IRIS. P. jirovecii pneumonia is known to be associated with the development of IRIS, which is a paradoxical clinical deterioration correlating with rising cell count and reconstitution after the initiation of ART. Patients who are successfully treated with antimicrobials and have a baseline CD4 count less than 200 cells/ml at the time of ART initiation are susceptible to developing IRIS.9 IRIS presents with varying symptoms including recurrent fever, increased cough, dyspnea, hypoxemia, and progressive radiologic findings of ARDS.9 This patient’s acute respiratory failure after an initial improvement again was diagnosed as probably IRIS, however, potentially could alternatively be explained by rapid pulmonary recruitment of newly competent immune and inflammatory cells in response to a few persistent Pneumocystis organisms, thus resulting in inflammatory damage to the lung.10 A comprehensive literature search provided four other cases of respiratory failure caused by PJP in HIV/AIDS patients treated with ECMO (see Table 1). Our patient is the only case who also presented with IRIS. Most reported cases utilized VV ECMO, with the exception of the patient presented by Goodman et al, who was on veno-arterial ECMO. All of these patients were severely immunosuppressed, evidenced by their low CD4 count and high viral loads. All the patients who survived had ART initiated after ECMO. ECMO may thus be a feasible salvage modality in immunocompromised patients in ARDS, if started early in the course of their hypoxemic respiratory failure. Conclusions The use of ECMO has been rising in the past decade, such that more experienced centers are offering the therapy to increasingly medically complex patients with ARDS. If ECMO is started early in the course of disease, it may still be a viable salvage modality even in those who were previously considered less likely to benefit, such as patients with AIDS and/or pneumocystis pneumonia. Given the improvement in management of patients with HIV, this diagnosis should not be considered a relative contraindication to offering ECMO. Further studies are needed to understand how to best utilize and optimize ECMO therapy in patients with severe immunosuppression.
References 1. Roembke F, Heinzow HS, Gosseling T, et al: Clinical outcome and predictors of survival in patients with pneumocystis jirovecii pneumonia–results of a tertiary referral centre. Clin Respir J 8: 86–92, 2014. 2. Barbier F, Coquet I, Legriel S, et al: Etiologies and outcome of acute respiratory failure in HIV-infected patients. Intensive Care Med 35: 1678–1686, 2009. 3. Rollins MD, Hubbard A, Zabrocki L, Barnhart DC, Bratton SL: Extracorporeal membrane oxygenation cannulation trends for pediatric respiratory failure and central nervous system injury. J Pediatr Surg 47: 68–75, 2012. 4. Combes A, Bacchetta M, Brodie D, Müller T, Pellegrino V: Extracorporeal membrane oxygenation for respiratory failure in adults. Curr Opin Crit Care 18: 99–104, 2012. 5. Patroniti N, Zangrillo A, Pappalardo F, et al: The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks. Intensive Care Med 37: 1447–1457, 2011. 6. Peek GJ, Clemens F, Elbourne D, et al: CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure. BMC Health Serv Res 6: 163, 2006. 7. Finney SJ, Cordingley JJ, Griffiths MJ, Evans TW: ECMO in adults for severe respiratory failure finally comes of age: just in time? Thorax 65: 194–195, 2010. 8. Rodger AJ, Lodwick R, Schechter M, et al; INSIGHT SMART, ESPRIT Study Groups: Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 27: 973–979, 2013. 9. Barry SM, Lipman MC, Deery AR, Johnson MA, Janossy G: Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects. HIV Med 3: 207– 211, 2002. 10. Wislez M, Bergot E, Antoine M, et al: Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 164: 847–851, 2001. 11. Goodman JLG, Satish S, Michael F, Mark L, Jose B: Extracorporeal membrane oxygenation as adjustive therapy for refractory hypoxemic respiratory failure in HIV-positive patients with severe Pneumocystis jirovecii pneumonia. Clin Pulm Med 20: 117–120, 2013. 12. Gutermann H, van Roy B, Meersseman W, Meyns B, Herijgers P: Successful extracorporeal lung assistance for overwhelming pneumonia in a patient with undiagnosed full blown aids–a controversial therapy in HIV-patients. Thorac Cardiovasc Surg 53: 252–254, 2005. 13. Steppan J, Sikazwe I. Extra-corporeal Membrane Oxygenation In An Adult With Severe Pneumocystis Pneumonia [Abstract]. Baltimore, MD: American College of Physicians Meeting; 2009.
Case Reports
The Use of ECMO in HIV/AIDS with Pneumocystis jirovecii Pneumonia: A Case Report and Review of the Literature Kelly Cawcutt,*† Alice Gallo De Moraes,* Sarah J. Lee,* John G. Park,* Gregory J. Schears,‡ and Michael E. Nemergut ‡
There are few reports of extracorporeal membrane oxygenation (ECMO) therapy for respiratory failure because of Pneumocystis jirovecii pneumonia (PJP) in patients with acquired immunodeficiency syndrome (AIDS). None of the cases reported involvement of immune reconstitution inflammatory syndrome (IRIS), a paradoxical clinical worsening after the initiation of antiretroviral therapy (ART) in ART-naïve patients because of an exaggerated systemic inflammation with cell count recovery. We present a patient with newly diagnosed AIDS and PJP pneumonia that progressed to acute respiratory distress syndrome (ARDS) secondary to probable IRIS for which veno-venous ECMO was initiated. He transitioned to conventional ventilator after 57 days of ECMO therapy. However, he did not survive to hospital discharge. Combined with four previously reported cases of ARDS in human immunodeficiency virus patients secondary to PJP treated with ECMO, three of the five patients survived to ECMO decannulation. Extracorporeal membrane oxygenation is considered an accepted modality for adult patients with respiratory and/or cardiac failure refractory to maximal medical therapy. As ECMO becomes increasingly utilized in clinical practice, there is ongoing controversy regarding the appropriate selection of patients. In the past, contraindications to ECMO included immunocompromised states and conditions with known poor prognosis. The cases herein suggest the indications and contraindications warrant further discussion and research. ASAIO Journal 2014; 60:606–608.
in human immunodeficiency virus (HIV)-infected patients.1 In 2010, there was an estimated 47,230 new HIV/acquired immunodeficiency syndrome (AIDS) diagnosis in the United States.2 PJP accounted for 35% of cases with respiratory failure among HIV/AIDS patients admitted to the intensive care unit.2 There are a few reported cases of respiratory failure because of PJP requiring extracorporeal membrane oxygenation (ECMO) therapy. None had concurrent immune reconstitution inflammatory syndrome (IRIS). We present a case with a newly diagnosed AIDS, PJP pneumonia, and probable IRIS whose condition progressed to refractory acute respiratory distress syndrome (ARDS), for which veno-venous (VV) ECMO was required. We also review four published cases in which ECMO was used in adult AIDS patients with severe hypoxemia from PJP. Case Description A 45-year-old man presented to an outpatient clinic with fever, productive cough, and generalized weakness. He was treated empirically for community-acquired pneumonia and steadily worsened despite a 10 day course of amoxicillin-clavulanate. He was ultimately hospitalized and tested positive for HIV with CD4 count of 33 cells/ml (Figure 1). Bronchoalveolar lavage demonstrated P. jirovecii by polymerase chain reaction testing, for which he was initiated on trimethoprim/ sulfamethoxazole (TMP/SMX). He had hypoxia with an alveolar-arterial oxygen gradient of 26 but required persistent supplemental oxygen. Therefore, he was given prednisone. Efavirenz/emtricitabine/tenofovir (Atripla[AQ: Please provide
Key Words: critical care, case report, extracorporeal membrane oxygenation, acquired immunodeficiency syndrome, Pneumocystis jirovecii pneumonia, immune reconstitution inflammatory syndrome, human immunodeficiency virus
Pneumocystis jirovecii pneumonia (PJP, previously classified
as Pneumocystis carinii) is one of the leading causes of mortality
From the *Department of Medicine, Division of Pulmonary and Critical Care, Mayo Clinic, Rochester, Minnesota; †Department of Medicine, Division of Infectious Disease, Mayo Clinic, Rochester, Minnesota; and ‡Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota. Submitted for consideration April 2014; accepted for publication in revised form May 2014. Disclosure: This article was supported by the Division of Critical Care and by the Department of Anesthesiology with no direct financial support. Correspondence: Michael E. Nemergut, Department of Anesthesiology, Mayo Clinic, 200 First St SW, Rochester, MN 55905. Email: [email protected]. Copyright © 2014 by the American Society for Artificial Internal Organs Figure 1. Admission chest x-ray.
DOI: 10.1097/MAT.0000000000000112
606
USE OF EXTRACORPOREAL MEMBRANE OXYGENATION IN HIV/AIDS WITH PJP PNEUMONIA
manufacturer information (city, state, country if outside US) for Atripla.]) was then started for treatment of AIDS. He was discharged from the hospital after 6 days with a plan to complete a 3 week course of TMP/SMX with a prednisone taper, continue efavirenz/emtricitabine/tenofovir combined with prophylactic fluconazole and azithromycin. Approximately 1 week later, he was readmitted to the hospital with acute hypoxic respiratory failure requiring intubation and mechanical ventilation (Figure 2: chest x-ray on readmission). He was started on vancomycin, levofloxacin, piperacillintazobactam, and approximately 0.75 mg/kg of methylprednisolone IV per day. Trimethoprim/sulfamethoxazole therapy was also continued. Despite these therapies, his respiratory status deteriorated with worsening hypoxia. The Infectious Disease consult team felt he likely developed IRIS given the timing of respiratory decompensation in respect to the initiation of antiretroviral therapy (ART), demonstration of medical compliance with TMP/SMX therapy by serum drug levels, and lack of another new identified pathogen besides Pneumocystis. Thus, corticosteroid dosing was increased to approximately 1.5 mg/kg per day. Unfortunately, he developed ARDS refractory to all attempted therapies including lung-protective ventilation, prone positioning, neuromuscular blocking agents, and inhaled alprostadil. Despite these maneuvers, arterial blood gas analysis showed persistent hypoxia (PaO2 of 50 mmHg) on 100% fraction of inspired oxygen (FiO2), positive endexpiratory pressure (PEEP) of 15, resulting in PaO2 to FiO2 ratio of 50. A 31-French Avalon VV ECMO catheter was placed into the right internal jugular vein under sterile conditions in the operating room. He was subsequently initiated with circuit flow of 4 l/min and sweep of 4 l/min of oxygen (100% FiO2). The cannula exit sites were managed through the standard protocol for our institution, which includes insertion with initial chlorhexidine cleansing, use of maximal sterile barriers, suture securement, and repeat preparation of the insertion site with chlorhexidine at the end of the procedure and Tegaderm dressing. If the dressing does not become compromised, it is changed every 7 days.
Figure 2. Readmission chest x-ray.
607
Concurrent ventilator settings included a tidal volume of 300 ml, respiratory rate of 20 bpm, PEEP of 10 mmHg, and FiO2 of 80%. Resultant ABG revealed a pH of 7.27, PCO2 of 53 mmHg, PaO2 of 64 mmHg, base excess of −3, and SpO2 saturation of 88.5%. Antiretroviral therapy was discontinued the day after ECMO initiation secondary to concerns for poor absorption because of ileus and possible toxicity given his acute kidney injury but was restarted approximately 1 week later when ileus improved and never required dialysis. Extracorporeal membrane oxygenation was at maximum setting during the first week with the circuit flow at approximately 4 l/min and oxygen sweep of 11 L/min (100% FiO2), whereas on bilevel mechanical ventilation with settings of PEEPhigh of 26 mmHg, PEEPlow of 10 mmHg, PS of 10, and FiO2 of 100%. Despite high FiO2, his oxygen saturation remained in the 80–85% range on arterial blood samples for the first 10 days on ECMO. Subsequently, ECMO support was slowly weaned while he continued on his antiretroviral medications and therapy for PJP with corticosteroids, TMP/SMX, clindamycin, and primaquine. The patient’s clinical course was further complicated by the development of bilateral pneumothoraces requiring chest tube placements, intracranial hemorrhagic mass of unknown etiology, bacteremia, and critical illness myopathy. The intracranial hemorrhagic mass lesion was 1.4 × 1.2 cm in size. The heparin dose was 1700 U/hr at the time of diagnosis and was not changed in direct response to this finding. A repeat computed tomography scan of his head was completed on days 3 and 7 after the event with no evidence of increased hemorrhage around the lesion. After 57 days on ECMO, as his oxygenation improved, he was successfully decannulated. He was transferred out of the intensive care unit to a chronic ventilator unit but ultimately succumbed to multiorgan failure combined with his other comorbidities on hospital day 97. Discussion ECMO is becoming an accepted salvage therapy for respiratory and/or circulatory failure refractory to maximal medical therapy.3 Favorable outcomes in severe ARDS have been reported with ECMO use during the 2009 H1N1 influenza pandemic and in the CESAR trial, which led to increased interest and use of ECMO for refractory respiratory failure.4,5,6 As ECMO becomes increasingly utilized in clinical practice, guidelines for its use in medically complex adult patients are absent, and the literature for its use in severe refractory ARDS is limited.7 ECMO guidelines have listed major immunodeficiency states and comorbidities associated with poor outcomes as relative contraindications. Similarly, severe PJP requiring mechanical ventilation was previously thought to be medically futile. However, with the advent of new antiretroviral medications and initiatives to improve diagnostic testing and medication compliance, HIV/ AIDS can be managed as a chronic condition, particularly because these patients have similar life expectancy to the general population.8 Therefore, AIDS or PJP should not be a contraindication for the use of ECMO. In addition, numerous advances in materials and ECMO circuit design have allowed the utilization of this support technology in higher risk patients with less complications, thus the guidelines for its use need to be reconsidered.4
608 CAWCUTT et al. Table 1. Patients with Respiratory Failure Caused by Pneumocystis jirovecii Pneumonia Treated with ECMO
Age (y)/Sex
CD4 (cells/ ml)
HIV Viral Load (copies/ ml)
Timing of ART Initiation (Pre-, On-, Post-ECMO)
PaO2 (mmHg)/ FiO2 (%)
ECMO Initiation (hospital day)/ Duration (days)
1 (our patient)
45/M
33
113,000
Pre
59/60
5/57
2 (Goodman et al)11
30/F
13
976,631
Post
50.1/100
3/7
3 (Gutermann et al)12
55/M
9
80,235
Post
NR/NR
4/4
4 (Steppan)13 5 (Goodman et al)11
39/M 25/M
69 36
6297 622,234
Pre Pre
NR/100 63.6/100
12/14 18/69
Patient (Ref)
Outcome Died in hospital, after decannulation Survived to hospital discharge Survived to hospital discharge Died on ECMO Died on ECMO
ART, antiretroviral therapy; ECMO, extracorporeal membrane oxygenation; NR, not reported.
Our case was unique in that PJP and IRIS contributed to the ARDS presentation. To our knowledge, our case is the first reported use of ECMO for PJP in an AIDS patient complicated by IRIS. P. jirovecii pneumonia is known to be associated with the development of IRIS, which is a paradoxical clinical deterioration correlating with rising cell count and reconstitution after the initiation of ART. Patients who are successfully treated with antimicrobials and have a baseline CD4 count less than 200 cells/ml at the time of ART initiation are susceptible to developing IRIS.9 IRIS presents with varying symptoms including recurrent fever, increased cough, dyspnea, hypoxemia, and progressive radiologic findings of ARDS.9 This patient’s acute respiratory failure after an initial improvement again was diagnosed as probably IRIS, however, potentially could alternatively be explained by rapid pulmonary recruitment of newly competent immune and inflammatory cells in response to a few persistent Pneumocystis organisms, thus resulting in inflammatory damage to the lung.10 A comprehensive literature search provided four other cases of respiratory failure caused by PJP in HIV/AIDS patients treated with ECMO (see Table 1). Our patient is the only case who also presented with IRIS. Most reported cases utilized VV ECMO, with the exception of the patient presented by Goodman et al, who was on veno-arterial ECMO. All of these patients were severely immunosuppressed, evidenced by their low CD4 count and high viral loads. All the patients who survived had ART initiated after ECMO. ECMO may thus be a feasible salvage modality in immunocompromised patients in ARDS, if started early in the course of their hypoxemic respiratory failure. Conclusions The use of ECMO has been rising in the past decade, such that more experienced centers are offering the therapy to increasingly medically complex patients with ARDS. If ECMO is started early in the course of disease, it may still be a viable salvage modality even in those who were previously considered less likely to benefit, such as patients with AIDS and/or pneumocystis pneumonia. Given the improvement in management of patients with HIV, this diagnosis should not be considered a relative contraindication to offering ECMO. Further studies are needed to understand how to best utilize and optimize ECMO therapy in patients with severe immunosuppression.
References 1. Roembke F, Heinzow HS, Gosseling T, et al: Clinical outcome and predictors of survival in patients with pneumocystis jirovecii pneumonia–results of a tertiary referral centre. Clin Respir J 8: 86–92, 2014. 2. Barbier F, Coquet I, Legriel S, et al: Etiologies and outcome of acute respiratory failure in HIV-infected patients. Intensive Care Med 35: 1678–1686, 2009. 3. Rollins MD, Hubbard A, Zabrocki L, Barnhart DC, Bratton SL: Extracorporeal membrane oxygenation cannulation trends for pediatric respiratory failure and central nervous system injury. J Pediatr Surg 47: 68–75, 2012. 4. Combes A, Bacchetta M, Brodie D, Müller T, Pellegrino V: Extracorporeal membrane oxygenation for respiratory failure in adults. Curr Opin Crit Care 18: 99–104, 2012. 5. Patroniti N, Zangrillo A, Pappalardo F, et al: The Italian ECMO network experience during the 2009 influenza A(H1N1) pandemic: preparation for severe respiratory emergency outbreaks. Intensive Care Med 37: 1447–1457, 2011. 6. Peek GJ, Clemens F, Elbourne D, et al: CESAR: conventional ventilatory support vs extracorporeal membrane oxygenation for severe adult respiratory failure. BMC Health Serv Res 6: 163, 2006. 7. Finney SJ, Cordingley JJ, Griffiths MJ, Evans TW: ECMO in adults for severe respiratory failure finally comes of age: just in time? Thorax 65: 194–195, 2010. 8. Rodger AJ, Lodwick R, Schechter M, et al; INSIGHT SMART, ESPRIT Study Groups: Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population. AIDS 27: 973–979, 2013. 9. Barry SM, Lipman MC, Deery AR, Johnson MA, Janossy G: Immune reconstitution pneumonitis following Pneumocystis carinii pneumonia in HIV-infected subjects. HIV Med 3: 207– 211, 2002. 10. Wislez M, Bergot E, Antoine M, et al: Acute respiratory failure following HAART introduction in patients treated for Pneumocystis carinii pneumonia. Am J Respir Crit Care Med 164: 847–851, 2001. 11. Goodman JLG, Satish S, Michael F, Mark L, Jose B: Extracorporeal membrane oxygenation as adjustive therapy for refractory hypoxemic respiratory failure in HIV-positive patients with severe Pneumocystis jirovecii pneumonia. Clin Pulm Med 20: 117–120, 2013. 12. Gutermann H, van Roy B, Meersseman W, Meyns B, Herijgers P: Successful extracorporeal lung assistance for overwhelming pneumonia in a patient with undiagnosed full blown aids–a controversial therapy in HIV-patients. Thorac Cardiovasc Surg 53: 252–254, 2005. 13. Steppan J, Sikazwe I. Extra-corporeal Membrane Oxygenation In An Adult With Severe Pneumocystis Pneumonia [Abstract]. Baltimore, MD: American College of Physicians Meeting; 2009.
