Neurocrit Care DOI 10.1007/s12028-015-0115-z
PRACTICAL PEARL
Transfusion-Related Acute Lung Injury After IVIG for Myasthenic Crisis Dereddi Raja S. Reddy • Pramod K. Guru • Melissa M. Blessing • James R. Stubbs • Alejandro A. Rabinstein • Eelco F. M. Wijdicks
Ó Springer Science+Business Media New York 2015
Abstract Background A 26-year-old female with myasthenic crisis developed transfusion-related acute lung injury (TRALI) after she was treated with intravenous immunoglobulin. Methods Case report. Results Respiratory status markedly worsened with each intravenous immunoglobulin (IVIG) administration and progressing from a need to use bilevel positive airway pressure (BiPAP) to intubation. Pulmonary function tests improved during this episode. Conclusions IVIG may cause TRALI and due to subtle clinical findings can be mistaken for neuromuscular respiratory failure. Keywords Acute lung injury Transfusion-related acute lung injury Myasthenia Critical care Intravenous immunoglobulin therapy
D. R. S. Reddy (&) P. K. Guru Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW RO_OL_2_115CCS, Rochester, MN 55905, USA e-mail: [email protected] M. M. Blessing J. R. Stubbs Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA A. A. Rabinstein E. F. M. Wijdicks Division of Critical Care Neurology, Mayo, Rochester, MN, USA
Case Presentation A 26-year-old female with myasthenia gravis was treated with antibiotics, methylprednisone, pyridostigmine, and intravenous immunoglobulin (IVIG) for an exacerbation precipitated by community acquired pneumonia. Two hours after the 1st dose of IVIG, she became tachypneic and hypoxemic and was transitioned from 2 L oxygen via nasal cannula to bilevel positive airway pressure (BiPAP) ventilation (Fig. 1). She had symptomatic improvement and was weaned back to nasal cannula. Her respiratory status again deteriorated after the second dose of IVIG therapy; the next day, however, her bedside pulmonary function tests improved. She required re-institution of BiPAP. Her chest X-ray showed features consistent with pulmonary edema, but she had no response to a diuretic challenge. Her myasthenic symptoms showed signs of improvement and she never needed any regular suctioning for secretion burden; therefore, she was planned for a total of five doses of IVIG therapy. However, after her third dose of IVIG, she had respiratory decompensation which required up titration to double flow closed face mask. Repeat challenge with diuretic therapy also had no clinical response. Cardiac and infectious causes were excluded by a normal echocardiogram and negative cultures. Her repeat bedside pulmonary functions tests (vital capacity, maximum inspiratory, and expiratory pressures) were improving and showed no decline. And after the fourth dose of IVIG, she had profound hypoxemic respiratory failure, and non-invasive positive pressure ventilator support was deemed inadequate, mandating mechanical ventilation. Because of the clear temporal correlation between her acute respiratory failure and the administration of IVIG, we diagnosed her with transfusion-related acute lung injury (TRALI). The diagnosis of TRALI was made after excluding hydrostatic lung
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Neurocrit Care
Fig. 1 IVIG infusion graphs
edema based on a normal echocardiogram and failure to respond to diuretic challenge, negative pan cultures, improving bedside pulmonary function tests, and stable antibiotic regime. Her repeated need for supplemental oxygen therapy, tachypnea, and non-invasive ventilatory support point toward reduced static lung compliance consistent with acute lung injury (ALI) which we therefore attributed to IVIG. Patient experienced a brief seizure prior to intubation and hours later developed hypotension and a repeat echocardiogram showed features of stress cardiomyopathy (SCM). Although SCM can be caused by myasthenia crisis itself [1, 2] or even the brief seizure [3], we attributed SCM to the overall stress of the illness. There were no further episodes of seizures and her ejection fraction improved during hospitalization.
Discussion TRALI, a serious condition rarely encountered by neurologists in daily practice, is the leading cause of transfusion-related mortality according to the US Food and Drug Administration reports [4]. The Centers for Disease Control and Prevention (CDC) diagnostic criteria include no evidence of ALI prior to transfusion, ALI onset within 6 h of transfusion, hypoxemia, bilateral infiltrates on radiograph, and no evidence of circulatory overload [5].
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Although bilateral pulmonary infiltrates should be present on chest radiograph for the definition of TRALI, these abnormalities may be subtle or even absent [6, 7]. A two-hit hypothesis has been proposed for TRALI. The first hit is any underlying patient factor like inflammation or infection resulting in adherence of primed neutrophils to the pulmonary endothelium. The second hit is caused by mediators in the transfused blood product that activate the endothelial cells and pulmonary neutrophils, resulting in capillary leakage and subsequent pulmonary edema. These second hit mediators can be due to antibodies or biologically active lipids that accumulate during storage of blood products. Human leukocyte antigens (HLA) or human neutrophil antigens (HNA), prevalent in multiparous females, may contribute to the second hit. The recent emphasis on female donor exclusion has significantly reduced TRALI incidence [7]. TRALI is a clinical diagnosis of exclusion and no confirmatory diagnostic tests are available. No definitive treatment exists and the management is primarily supportive. Some patients with mild TRALI will only need supplemental oxygen, while in 70–90 % of patients mechanical ventilation is unavoidable. The prognosis is generally good and most patients recover within 72 h [7]. The first reported case of TRALI after IVIG administration was in a 23-year-old male being treated for multifocal motor neuropathy with conduction block [8].
Neurocrit Care
Although there are few reported cases of TRALI after IVIG use [9, 10], the best of our knowledge this is the first reported case during myasthenic crisis.
Conclusion Thus, it is important for neurologists to remember including IVIG-associated TRALI in the differential diagnosis of any myasthenic patient who has rapid respiratory worsening while being treated with IVIG. If not fulminant, recognizing TRALI can be a challenge. Herein, subtle increase in oxygen requirements, repeatedly and incrementally, pointed to the diagnosis which was only recognized after several episodes of increasing respiratory worsening with repeated doses of IVIG. Most neurologists would first consider worsening neuromuscular respiratory failure; measurement of pulmonary muscle strength and repeating a chest X-ray for new infiltrates may be helpful in differentiating the two.
References 1. Beydoun, et al. Emotional stress as a trigger of myasthenic crisis and concomitant takotsubo cardiomyopathy: a case report. J Med Case Rep. 2010;4:393.
2. Bijulal S, Harikrishnan S, Namboodiri N, Ajitkumar VK, Gupta D, Mathuranath PS. Tako-tsubo cardiomyopathy in a patient with myasthenia gravis crisis: a rare clinical association. BMJ Case Rep. 2009. 2009;. doi:10.1136/bcr06.2008.0182. 3. Santoro Francesco, Carapelle Elena, Ortiz Sofia Isabel Cieza, Musaico Francesco, Ferraretti Armando, d’Orsi Giuseppe, Specchio Luigi Maria, Di Biase Matteo, Brunetti Natale Daniele. Potential links between neurological disease and Tako-Tsubo cardiomyopathy: a literature review. Int J Cardiol. 2013;168: 688–91. 4. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ ReportaProblem/TransfusionDonationFatalities/ucm391574.htm. Accessed 8 Feb 2014. 5. http://www.cdc.gov/nhsn/PDFs/Biovigilance/BV-HV-protocolcurrent.pdf. Accessed 8 Apr 2014. 6. Sayah DM, Looney MR, Toy P. Transfusion reactions: newer concepts on the pathophysiology, incidence, treatment, and prevention of transfusion-related acute lung injury. Crit Care Clin. 2012;28(3):363–72. 7. Vlaar APJ, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet. 2013;382:984–94. 8. Rizk A, Gorson KC, Kenney L, Weinstein R. Transfusion-related acute lung injury after the infusion of IVIG. Transfusion. 2001; 41:264–8. 9. Stoclin A, Delbos F, Dauriat G, et al. Transfusion-related acute lung injury after intravenous immunoglobulin treatment in a lung transplant recipient. Vox Sang. 2013;104:175–8. 10. Berger-Achituv S, Ellis MH, Curtis BR, et al. Transfusion related acute lung injury following intravenous anti-D administration in an adolescent. Am J Hematol. 2008;83:676–8.
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PRACTICAL PEARL
Transfusion-Related Acute Lung Injury After IVIG for Myasthenic Crisis Dereddi Raja S. Reddy • Pramod K. Guru • Melissa M. Blessing • James R. Stubbs • Alejandro A. Rabinstein • Eelco F. M. Wijdicks
Ó Springer Science+Business Media New York 2015
Abstract Background A 26-year-old female with myasthenic crisis developed transfusion-related acute lung injury (TRALI) after she was treated with intravenous immunoglobulin. Methods Case report. Results Respiratory status markedly worsened with each intravenous immunoglobulin (IVIG) administration and progressing from a need to use bilevel positive airway pressure (BiPAP) to intubation. Pulmonary function tests improved during this episode. Conclusions IVIG may cause TRALI and due to subtle clinical findings can be mistaken for neuromuscular respiratory failure. Keywords Acute lung injury Transfusion-related acute lung injury Myasthenia Critical care Intravenous immunoglobulin therapy
D. R. S. Reddy (&) P. K. Guru Division of Pulmonary and Critical Care Medicine, Mayo Clinic, 200 First Street SW RO_OL_2_115CCS, Rochester, MN 55905, USA e-mail: [email protected] M. M. Blessing J. R. Stubbs Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA A. A. Rabinstein E. F. M. Wijdicks Division of Critical Care Neurology, Mayo, Rochester, MN, USA
Case Presentation A 26-year-old female with myasthenia gravis was treated with antibiotics, methylprednisone, pyridostigmine, and intravenous immunoglobulin (IVIG) for an exacerbation precipitated by community acquired pneumonia. Two hours after the 1st dose of IVIG, she became tachypneic and hypoxemic and was transitioned from 2 L oxygen via nasal cannula to bilevel positive airway pressure (BiPAP) ventilation (Fig. 1). She had symptomatic improvement and was weaned back to nasal cannula. Her respiratory status again deteriorated after the second dose of IVIG therapy; the next day, however, her bedside pulmonary function tests improved. She required re-institution of BiPAP. Her chest X-ray showed features consistent with pulmonary edema, but she had no response to a diuretic challenge. Her myasthenic symptoms showed signs of improvement and she never needed any regular suctioning for secretion burden; therefore, she was planned for a total of five doses of IVIG therapy. However, after her third dose of IVIG, she had respiratory decompensation which required up titration to double flow closed face mask. Repeat challenge with diuretic therapy also had no clinical response. Cardiac and infectious causes were excluded by a normal echocardiogram and negative cultures. Her repeat bedside pulmonary functions tests (vital capacity, maximum inspiratory, and expiratory pressures) were improving and showed no decline. And after the fourth dose of IVIG, she had profound hypoxemic respiratory failure, and non-invasive positive pressure ventilator support was deemed inadequate, mandating mechanical ventilation. Because of the clear temporal correlation between her acute respiratory failure and the administration of IVIG, we diagnosed her with transfusion-related acute lung injury (TRALI). The diagnosis of TRALI was made after excluding hydrostatic lung
123
Neurocrit Care
Fig. 1 IVIG infusion graphs
edema based on a normal echocardiogram and failure to respond to diuretic challenge, negative pan cultures, improving bedside pulmonary function tests, and stable antibiotic regime. Her repeated need for supplemental oxygen therapy, tachypnea, and non-invasive ventilatory support point toward reduced static lung compliance consistent with acute lung injury (ALI) which we therefore attributed to IVIG. Patient experienced a brief seizure prior to intubation and hours later developed hypotension and a repeat echocardiogram showed features of stress cardiomyopathy (SCM). Although SCM can be caused by myasthenia crisis itself [1, 2] or even the brief seizure [3], we attributed SCM to the overall stress of the illness. There were no further episodes of seizures and her ejection fraction improved during hospitalization.
Discussion TRALI, a serious condition rarely encountered by neurologists in daily practice, is the leading cause of transfusion-related mortality according to the US Food and Drug Administration reports [4]. The Centers for Disease Control and Prevention (CDC) diagnostic criteria include no evidence of ALI prior to transfusion, ALI onset within 6 h of transfusion, hypoxemia, bilateral infiltrates on radiograph, and no evidence of circulatory overload [5].
123
Although bilateral pulmonary infiltrates should be present on chest radiograph for the definition of TRALI, these abnormalities may be subtle or even absent [6, 7]. A two-hit hypothesis has been proposed for TRALI. The first hit is any underlying patient factor like inflammation or infection resulting in adherence of primed neutrophils to the pulmonary endothelium. The second hit is caused by mediators in the transfused blood product that activate the endothelial cells and pulmonary neutrophils, resulting in capillary leakage and subsequent pulmonary edema. These second hit mediators can be due to antibodies or biologically active lipids that accumulate during storage of blood products. Human leukocyte antigens (HLA) or human neutrophil antigens (HNA), prevalent in multiparous females, may contribute to the second hit. The recent emphasis on female donor exclusion has significantly reduced TRALI incidence [7]. TRALI is a clinical diagnosis of exclusion and no confirmatory diagnostic tests are available. No definitive treatment exists and the management is primarily supportive. Some patients with mild TRALI will only need supplemental oxygen, while in 70–90 % of patients mechanical ventilation is unavoidable. The prognosis is generally good and most patients recover within 72 h [7]. The first reported case of TRALI after IVIG administration was in a 23-year-old male being treated for multifocal motor neuropathy with conduction block [8].
Neurocrit Care
Although there are few reported cases of TRALI after IVIG use [9, 10], the best of our knowledge this is the first reported case during myasthenic crisis.
Conclusion Thus, it is important for neurologists to remember including IVIG-associated TRALI in the differential diagnosis of any myasthenic patient who has rapid respiratory worsening while being treated with IVIG. If not fulminant, recognizing TRALI can be a challenge. Herein, subtle increase in oxygen requirements, repeatedly and incrementally, pointed to the diagnosis which was only recognized after several episodes of increasing respiratory worsening with repeated doses of IVIG. Most neurologists would first consider worsening neuromuscular respiratory failure; measurement of pulmonary muscle strength and repeating a chest X-ray for new infiltrates may be helpful in differentiating the two.
References 1. Beydoun, et al. Emotional stress as a trigger of myasthenic crisis and concomitant takotsubo cardiomyopathy: a case report. J Med Case Rep. 2010;4:393.
2. Bijulal S, Harikrishnan S, Namboodiri N, Ajitkumar VK, Gupta D, Mathuranath PS. Tako-tsubo cardiomyopathy in a patient with myasthenia gravis crisis: a rare clinical association. BMJ Case Rep. 2009. 2009;. doi:10.1136/bcr06.2008.0182. 3. Santoro Francesco, Carapelle Elena, Ortiz Sofia Isabel Cieza, Musaico Francesco, Ferraretti Armando, d’Orsi Giuseppe, Specchio Luigi Maria, Di Biase Matteo, Brunetti Natale Daniele. Potential links between neurological disease and Tako-Tsubo cardiomyopathy: a literature review. Int J Cardiol. 2013;168: 688–91. 4. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/ ReportaProblem/TransfusionDonationFatalities/ucm391574.htm. Accessed 8 Feb 2014. 5. http://www.cdc.gov/nhsn/PDFs/Biovigilance/BV-HV-protocolcurrent.pdf. Accessed 8 Apr 2014. 6. Sayah DM, Looney MR, Toy P. Transfusion reactions: newer concepts on the pathophysiology, incidence, treatment, and prevention of transfusion-related acute lung injury. Crit Care Clin. 2012;28(3):363–72. 7. Vlaar APJ, Juffermans NP. Transfusion-related acute lung injury: a clinical review. Lancet. 2013;382:984–94. 8. Rizk A, Gorson KC, Kenney L, Weinstein R. Transfusion-related acute lung injury after the infusion of IVIG. Transfusion. 2001; 41:264–8. 9. Stoclin A, Delbos F, Dauriat G, et al. Transfusion-related acute lung injury after intravenous immunoglobulin treatment in a lung transplant recipient. Vox Sang. 2013;104:175–8. 10. Berger-Achituv S, Ellis MH, Curtis BR, et al. Transfusion related acute lung injury following intravenous anti-D administration in an adolescent. Am J Hematol. 2008;83:676–8.
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