LETTERS Extracorporeal Life Support To the Editor: Munshi and colleagues recently reported a review and metaanalysis of extracorporeal life support (ECLS) for respiratory failure in adults (ARDS) (1). They analyzed 10 published studies comparing patients managed with ECLS to those managed with conventional care (2–11). They concluded that there was no survival benefit with ECLS, except in some subgroups. However, 5 of the 10 studies did not compare similar cohorts of patients, which is essential for metaanalysis. Two of the 10 studies were randomized controlled trials done more than 20 years ago using techniques of conventional care and ECLS that are not relevant today. The remaining three studies are valid studies of current technology. These three studies show a significant survival benefit to ECLS, individually and in aggregate. Five of the studies described single-center experience with all patients with ARDS and compared the patients who were successfully managed with conventional care to those who failed to improve with conventional care and went on to ECLS. Each center reported the method for identifying the patients with the highest mortality risk (indications for ECLS) and an algorithm for proceeding to ECLS. The patients receiving ECLS and non-ECLS conventional care represent sequential arms of a care protocol. The groups are not comparable, and metaanalysis is not appropriate (2–6). Two of the reports described the National Institutes of Health randomized trial of extracorporeal membrane oxygenation in ARDS in the 1970s (7) and the single-center randomized trial of extracorporeal CO2 removal reported in 1994 (8). Both of these trials were done in centers without significant experience in ECLS, using techniques of ECLS and conventional care that would not be used today. The three reports of valid comparative studies of modern technology are the prospective randomized CESAR (Conventional Care versus Extracorporeal Support in Adult Respiratory Failure) trial (9), and two matched-pairs studies of ECLS in ARDS due to H1N1 infection (10, 11). The CESAR trial in the UK showed that ARDS management in the ECLS center in Leicester resulted in 20% better survival than management in other non-ECLS centers. In that study, 83% of the patients randomized to the Leicester center were managed with ECLS, and 17% improved without meeting ECLS indications. Both matched-pairs trials showed significantly improved survival with ECLS, matched to similar patients receiving conventional care. We agree that more comparative trials of ECLS are desirable, particularly as both conventional care and ECLS methods are continuously evolving. However, the three valid studies that have been published all show a major survival benefit to ARDS management in centers with ECLS expertise. Author disclosures are available with the text of this letter at www.atsjournals.org. Robert H. Bartlett, M.D. University of Michigan Ann Arbor, Michigan
992
Alain Combes, M.D. Hopital Pitie-Salp ´ etri ˆ ere ` Paris, France Giles J. Peek, M.D. Glenfield Hospital Leicester, United Kingdom
References 1 Munshi L, Telesnicki T, Walkey A, Fan E. Extracorporeal life support for acute respiratory failure: a systematic review and meta-analysis. Ann Am Thorac Soc 2014;11:802–810. 2 Lewandowski K, Rossaint R, Pappert D, Gerlach H, Slama KJ, Weidemann H, Frey DJ, Hoffmann O, Keske U, Falke KJ. High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med 1997;23:819–835. 3 Mols G, Loop T, Geiger K, Farthmann E, Benzing A. Extracorporeal membrane oxygenation: a ten-year experience. Am J Surg 2000; 180:144–154. 4 Beiderlinden M, Eikermann M, Boes T, Breitfeld C, Peters J. Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange. Intensive Care Med 2006;32:1627– 1631. 5 Roch A, Lepaul-Ercole R, Grisoli D, Bessereau J, Brissy O, Castanier M, Dizier S, Forel JM, Guervilly C, Gariboldi V, et al. Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study. Intensive Care Med 2010;36:1899–1905. 6 Bein T, Weber-Carstens S, Goldmann A, M uller ¨ T, Staudinger T, Brederlau J, Muellenbach R, Dembinski R, Graf BM, Wewalka M, et al. Lower tidal volume strategy (z3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med 2013;39: 847–856. 7 Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, Morris AH, Peirce EC II, Thomas AN, Proctor HJ, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 1979;242:2193– 2196. 8 Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr, Weaver LK, Dean NC, Thomas F, East TD, Pace NL, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994;149:295–305. 9 Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, et al.; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009;374:1351–1363. 10 Pham T, Combes A, Roze´ H, Chevret S, Mercat A, Roch A, Mourvillier B, Ara-Somohano C, Bastien O, Zogheib E, et al.; REVA Research Network. Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2013;187:276–285. 11 Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011; 306:1659–1668. Copyright © 2014 by the American Thoracic Society
AnnalsATS Volume 11 Number 6 | July 2014
LETTERS Reply From the Authors: We thank Dr. Barlett and colleagues for their letter. We agree that extracorporeal life support (ECLS) has undergone substantial evolution since the initial studies from the 1970s. However, we were unable to identify a specific threshold at which “modern” ECLS began, with which we could limit our analysis (1). As with any systematic review, our approach was to develop an a priori search strategy to first capture all available studies of ECLS in acute respiratory failure and then explore any potential (and anticipated) heterogeneity through appropriate subgroup and sensitivity analysis. To that end, we performed a subgroup analysis including the studies highlighted by Bartlett and colleagues as “modern” venovenous extracorporeal membrane oxygenation (VV-ECMO) strategies (i.e., Peek and colleagues [2], Noah and colleagues [3], and Pham and colleagues [4]), which are currently considered the most valid studies of ECLS for acute respiratory distress syndrome (ARDS). The results of our subgroup analysis restricted to these more recent studies revealed that VV-ECMO may potentially be a promising option for the treatment of severe acute respiratory failure. However, our analysis also demonstrates the need for more research in this domain. We hope that the ongoing EOLIA (Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome) study (ClinicalTrials.gov NCT01470703) will provide more clarity regarding the use of VV-ECMO for severe ARDS.
Laveena Munshi, M.D. University of Toronto Toronto, Ontario, Canada Allan Walkey, M.D., M.Sc. Boston University School of Medicine Boston, Massachusetts Eddy Fan, M.D., Ph.D. University of Toronto Toronto, Ontario, Canada
References 1 Munshi L, Telesnicki T, Walkey A, Fan E. Extracorporeal life support for acute respiratory failure: a systematic review and meta-analysis. Ann Am Thorac Soc 2014;11:802–810. 2 Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, et al.; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374:1351–1363. 3 Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011;306:1659– 1668. 4 Pham T, Combes A, Roz e´ H, Chevret S, Mercat A, Roch A, Mourvillier B, Ara-Somohano C, Bastien O, Zogheib E, et al.; REVA Research Network. Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensitymatched analysis. Am J Respir Crit Care Med 2013;187:276– 285.
Author disclosures are available with the text of this letter at www.atsjournals.org.
Copyright © 2014 by the American Thoracic Society
Refractory Hypoxemia Due to Sodium Polystyrene Sulfonate (Kayexalate) Aspiration
patient. The diagnosis was proven on postmortem examination.
To the Editor: Aspiration of commonly prescribed medications in the form of pills, powders, aerosols, or liquids can produce a milieu of local and systemic adverse effects (1, 2). Oi in 1978 first described a case of neonatal death associated with sodium polystyrene sulfonate (Kayexylate) aspiration (3). Since then sporadic cases of pneumonitis, or bronchitis associated with aspiration of this substance have been reported incidentally in autopsy findings, and pathological specimens (4). Polystyrene sulfate aspiration was not directly attributed to immediate morbidity in any of these patients (4–6). Sodium polystyrene sulfonate is a cation-exchange resin that is suspended in a solution and given orally or by retention enema for the treatment of hyperkalemia in patients with renal insufficiency (7). A systematic review documented that polystyrene crystal deposition can lead to significant colitis in some patients (8). We report a case of severe acute respiratory distress syndrome (ARDS) that occurred as a direct result of sodium polystyrene sulfonate aspiration in an elderly Letters
Case Report An 89-year-old woman was hospitalized for worsening mental status, progressive weakness, and lethargy of 10 days’ duration. One week before admission, she was treated with ciprofloxacin for a urinary tract infection. She had a history of chronic obstructive pulmonary disease, coronary artery disease, and mild dementia. Her medical treatment included long-term use of supplemental oxygen administered via nasal cannula at a rate of 5 L/minute. At the time of admission, her blood pressure was 114/52 mm Hg; heart rate, 110 beats/minute; temperature, 37.18 C; respiratory rate, 28 breaths/minute. Her arterial oxygen saturation (as measured by pulse oximetry; SpO2) was 94% while she breathed oxygen at 5 L/minute. She appeared dehydrated and was somnolent. Auscultation of the lungs revealed decreased air entry in basilar lung fields bilaterally. Her physical examination was otherwise unremarkable. Laboratory analysis showed a white blood cell count of 22,000 cells/mm3; sodium, 993
LETTERS
Figure 1. ( A) Chest radiograph on presentation. (B) Aspiration and early development of bilateral infiltrates suggestive of acute respiratory distress syndrome.
The woman was sedated and paralyzed with cisatracurium and positive end-expiratory pressure was titrated incrementally up to 20 cm H2O. Despite these changes, the oxygen saturation remained low at 80–85%, and the plateau pressures remained above 35 cm H2O. Because of her age, and rapidly deteriorating hemodynamics, prone positioning, extracorporeal membrane oxygenation, and other salvage therapies were not offered. The patient developed refractory hypoxemia with multiorgan failure and refractory shock. The patient was transitioned to do-notresuscitate/comfort care (DNR-CC). She died shortly thereafter. On autopsy numerous foci of intraalveolar, large purple polygonal crystals, consistent with sodium polystyrene sulfonate aspiration were seen in all lung lobes and in the alveolar spaces of the patient’s lungs (Figure 2). These autopsy findings are similar to previous descriptions of sodium polystyrene sulfonate aspiration in the literature (9).
Discussion We report the first case in the English language literature of severe ARDS associated with aspiration of sodium polystyrene
4C/FPO
153 mmol/L; potassium, 6.9 mmol/L; blood urea nitrogen, 69 mg/dl; and creatinine, 1.93 mg/dl. A chest radiograph obtained at the time of admission showed no significant abnormalities (Figure 1A). Because of her elevated potassium, 30 g of sodium polystyrene sulfonate was administered orally. The patient vomited shortly after administration of the medication. She soon developed acute respiratory distress associated with severe hypoxemia. As a result of profound hypoxemia, she went into cardiac arrest with pulseless electrical activity. She received cardiopulmonary resuscitation for 20 minutes with a return of spontaneous circulation. The patient was intubated and transferred to the medical intensive care for further management. Her postintubation chest radiograph revealed extensive bilateral pulmonary infiltrates with new dense consolidation in the right upper lobe (Figure 1B). An arterial blood gas analysis performed while she breathed 100% oxygen revealed pH 7.07, PaCO2 94 mm Hg, and PaO2 67 mm Hg. The ratio of PaO2 to FIO2 (fraction of inspired oxygen) was 67. She was placed on volume-controlled ventilation with low tidal volumes (6 cm3/kg). Her lung compliance was 10 ml/cm H2O. Plateau pressures were as high as 40 cm H2O.
Figure 2. (A) Sodium polystyrene sulfonate (SPS) crystals and extensive alveolar damage. (B) Classic SPS polygonal crystals.
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AnnalsATS Volume 11 Number 6 | July 2014
LETTERS sulfonate. Previously reported episodes were reported as incidental findings on autopsy in patients with other acute illnesses such as bronchopneumonia and inhalational pneumonitis, without a temporal relationship to immediate polystyrene sulfonate administration (4–6). Haupt and Hutchins showed in an animal model that polystyrene sulfonate aspiration is accompanied by florid polymorphonuclear pulmonary infiltrates. These findings suggest that this resin can cause direct lung injury (10). As polystyrene sulfonate has been shown to be associated with alveolar injury in animal models, caution should be exercised when this medication is administered to patients at high risk for aspiration and ARDS. Our patient had a lung injury prediction score (LIPS) of 10 (11). After she aspirated, her respiratory status deteriorated over 2–4 hours and she developed refractory hypoxemia. The acute lung injury associated with extensive deposition of polystyrene sulfonate crystals in the alveoli, and subsequent changes to alveolar surfactant, could explain the sudden onset of this refractory hypoxemia. This has been described in detail in ARDS associated with other types of direct lung injuries (12). We acknowledge that lung injury is associated with a complex inflammatory response, and perhaps multiple insults are responsible for the development of ARDS in these patients (13). However, the extensive damage to the alveolar architecture found in close association with foci of polystyrene crystals at autopsy suggests that toxic effects of the aspirated cationic exchange resin either caused or substantially aggravated multiorgan dysfunction in this elderly patient with multiple comorbidities. Settings for mechanical ventilation of such patients should not necessarily differ from those recommended for ARDS associated with other causes: low tidal volume and open lung ventilation with supportive care should be provided to these patients (14). In patients who are hemodynamically stable and adequately oxygenated, bronchoscopy might be attempted to remove some of the crystals. The fulminant course of disease in our patient precluded any such therapeutic intervention. Our case highlights that in elderly debilitated patients with altered sensorium, aspiration of commonly prescribed drugs such as sodium polystyrene sulfonate can sometimes lead to devastating and even life-threatening effects. In these patients routes other than oral administration or alternative therapy should be considered. In our opinion all pulmonologists and intensivists should be cognizant of the consequence of accidental aspiration of sodium polystyrene sulfonate. Author disclosures are available with the text of this letter at www.atsjournals.org.
Letters
Acknowledgment: This work was performed in the Medical Intensive Care Unit, Cleveland Clinic Foundation, Cleveland, Ohio. Abhijit Duggal, M.D., M.P.H. Shameen Salam, M.D. Atul Mehta, M.D. Respiratory Institute, Cleveland Clinic Foundation Cleveland, Ohio
References 1 Kupeli ¨ E, Khemasuwan D, Lee P, Mehta AC. “Pills” and the air passages. Chest 2013;144:651–660. 2 Mehta AC, Khemasuwan D. A foreign body of a different kind: pill aspiration. Ann Thorac Med 2014;9:1–2. 3 Oi RH. The microscopic appearance of a sodium–potassium exchange resin in histologic sections. Am J Clin Pathol 1978;69:359–361. 4 Baiocchini A, Del Nonno F, De Nardo P, Bibas M. Pulmonary disease due to Kayexalate aspiration. Am J Med Sci 2013;345:149. 5 Gonzalez-Cuyar LF, Cresswell NB, Burke AP. Sodium polystyrene sulfonate (Kayexalate) aspiration. Diagn Pathol 2008;3:27. 6 Idowu MO, Mudge M, Ghatak NR. Kayexalate (sodium polystyrene sulfonate) aspiration. Arch Pathol Lab Med 2005;129:125. 7 Scherr L, Ogden DA, Mead AW, Spritz N, Rubin AL. Management of hyperkalemia with a cation-exchange resin. N Engl J Med 1961;264:115–119. 8 Harel Z, Harel S, Shah PS, Wald R, Perl J, Bell CM. Gastrointestinal adverse events with sodium polystyrene sulfonate (Kayexalate) use: a systematic review. Am J Med 2013;126:264.e9–24. 9 Fenton JJ, Johnson FB, Przygodzk RM, Kalasinsky VF, Al-Dayel F, Travis WD. Sodium polystyrene sulfonate (Kayexalate) aspiration: histologic appearance and infrared microspectrophotometric analysis of two cases. Arch Pathol Lab Med 1996;120:967–969. 10 Haupt HM, Hutchins GM. Sodium polystyrene sulfonate pneumonitis. Arch Intern Med 1982;142:379–381. 11 Gajic O, Dabbagh O, Park P, Adesanya A, Chang S, Hou P, Anderson H III, Hoth JJ, Mikkelsen ME, Gentile NT, et al.; U.S. Critical Illness and Injury Trials Group: Lung Injury Prevention Study Investigators (USCIITG-LIPS). Early identification of patients at risk of acute lung injury: evaluation of lung injury prediction score in a multicenter cohort study. Am J Respir Crit Care Med 2011; 183:462–470. 12 Stapleton RD, Wang BM, Hudson LD, Rubenfeld GD, Caldwell ES, Steinberg KP. Causes and timing of death in patients with ARDS. Chest 2005;128:525–532. 13 Petty TL, Silvers GW, Paul GW, Stanford RE. Abnormalities in lung elastic properties and surfactant function in adult respiratory distress syndrome. Chest 1979;75:571–574. 14 Fan E, Needham DM, Stewart TE. Ventilatory management of acute lung injury and acute respiratory distress syndrome. JAMA 2005; 294:2889–2896. Copyright © 2014 by the American Thoracic Society
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992
Alain Combes, M.D. Hopital Pitie-Salp ´ etri ˆ ere ` Paris, France Giles J. Peek, M.D. Glenfield Hospital Leicester, United Kingdom
References 1 Munshi L, Telesnicki T, Walkey A, Fan E. Extracorporeal life support for acute respiratory failure: a systematic review and meta-analysis. Ann Am Thorac Soc 2014;11:802–810. 2 Lewandowski K, Rossaint R, Pappert D, Gerlach H, Slama KJ, Weidemann H, Frey DJ, Hoffmann O, Keske U, Falke KJ. High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation. Intensive Care Med 1997;23:819–835. 3 Mols G, Loop T, Geiger K, Farthmann E, Benzing A. Extracorporeal membrane oxygenation: a ten-year experience. Am J Surg 2000; 180:144–154. 4 Beiderlinden M, Eikermann M, Boes T, Breitfeld C, Peters J. Treatment of severe acute respiratory distress syndrome: role of extracorporeal gas exchange. Intensive Care Med 2006;32:1627– 1631. 5 Roch A, Lepaul-Ercole R, Grisoli D, Bessereau J, Brissy O, Castanier M, Dizier S, Forel JM, Guervilly C, Gariboldi V, et al. Extracorporeal membrane oxygenation for severe influenza A (H1N1) acute respiratory distress syndrome: a prospective observational comparative study. Intensive Care Med 2010;36:1899–1905. 6 Bein T, Weber-Carstens S, Goldmann A, M uller ¨ T, Staudinger T, Brederlau J, Muellenbach R, Dembinski R, Graf BM, Wewalka M, et al. Lower tidal volume strategy (z3 ml/kg) combined with extracorporeal CO2 removal versus ‘conventional’ protective ventilation (6 ml/kg) in severe ARDS: the prospective randomized Xtravent-study. Intensive Care Med 2013;39: 847–856. 7 Zapol WM, Snider MT, Hill JD, Fallat RJ, Bartlett RH, Edmunds LH, Morris AH, Peirce EC II, Thomas AN, Proctor HJ, et al. Extracorporeal membrane oxygenation in severe acute respiratory failure. A randomized prospective study. JAMA 1979;242:2193– 2196. 8 Morris AH, Wallace CJ, Menlove RL, Clemmer TP, Orme JF Jr, Weaver LK, Dean NC, Thomas F, East TD, Pace NL, et al. Randomized clinical trial of pressure-controlled inverse ratio ventilation and extracorporeal CO2 removal for adult respiratory distress syndrome. Am J Respir Crit Care Med 1994;149:295–305. 9 Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, et al.; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009;374:1351–1363. 10 Pham T, Combes A, Roze´ H, Chevret S, Mercat A, Roch A, Mourvillier B, Ara-Somohano C, Bastien O, Zogheib E, et al.; REVA Research Network. Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensity-matched analysis. Am J Respir Crit Care Med 2013;187:276–285. 11 Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011; 306:1659–1668. Copyright © 2014 by the American Thoracic Society
AnnalsATS Volume 11 Number 6 | July 2014
LETTERS Reply From the Authors: We thank Dr. Barlett and colleagues for their letter. We agree that extracorporeal life support (ECLS) has undergone substantial evolution since the initial studies from the 1970s. However, we were unable to identify a specific threshold at which “modern” ECLS began, with which we could limit our analysis (1). As with any systematic review, our approach was to develop an a priori search strategy to first capture all available studies of ECLS in acute respiratory failure and then explore any potential (and anticipated) heterogeneity through appropriate subgroup and sensitivity analysis. To that end, we performed a subgroup analysis including the studies highlighted by Bartlett and colleagues as “modern” venovenous extracorporeal membrane oxygenation (VV-ECMO) strategies (i.e., Peek and colleagues [2], Noah and colleagues [3], and Pham and colleagues [4]), which are currently considered the most valid studies of ECLS for acute respiratory distress syndrome (ARDS). The results of our subgroup analysis restricted to these more recent studies revealed that VV-ECMO may potentially be a promising option for the treatment of severe acute respiratory failure. However, our analysis also demonstrates the need for more research in this domain. We hope that the ongoing EOLIA (Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome) study (ClinicalTrials.gov NCT01470703) will provide more clarity regarding the use of VV-ECMO for severe ARDS.
Laveena Munshi, M.D. University of Toronto Toronto, Ontario, Canada Allan Walkey, M.D., M.Sc. Boston University School of Medicine Boston, Massachusetts Eddy Fan, M.D., Ph.D. University of Toronto Toronto, Ontario, Canada
References 1 Munshi L, Telesnicki T, Walkey A, Fan E. Extracorporeal life support for acute respiratory failure: a systematic review and meta-analysis. Ann Am Thorac Soc 2014;11:802–810. 2 Peek GJ, Mugford M, Tiruvoipati R, Wilson A, Allen E, Thalanany MM, Hibbert CL, Truesdale A, Clemens F, Cooper N, et al.; CESAR trial collaboration. Efficacy and economic assessment of conventional ventilatory support versus extracorporeal membrane oxygenation for severe adult respiratory failure (CESAR): a multicentre randomised controlled trial. Lancet 2009; 374:1351–1363. 3 Noah MA, Peek GJ, Finney SJ, Griffiths MJ, Harrison DA, Grieve R, Sadique MZ, Sekhon JS, McAuley DF, Firmin RK, et al. Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1). JAMA 2011;306:1659– 1668. 4 Pham T, Combes A, Roz e´ H, Chevret S, Mercat A, Roch A, Mourvillier B, Ara-Somohano C, Bastien O, Zogheib E, et al.; REVA Research Network. Extracorporeal membrane oxygenation for pandemic influenza A(H1N1)-induced acute respiratory distress syndrome: a cohort study and propensitymatched analysis. Am J Respir Crit Care Med 2013;187:276– 285.
Author disclosures are available with the text of this letter at www.atsjournals.org.
Copyright © 2014 by the American Thoracic Society
Refractory Hypoxemia Due to Sodium Polystyrene Sulfonate (Kayexalate) Aspiration
patient. The diagnosis was proven on postmortem examination.
To the Editor: Aspiration of commonly prescribed medications in the form of pills, powders, aerosols, or liquids can produce a milieu of local and systemic adverse effects (1, 2). Oi in 1978 first described a case of neonatal death associated with sodium polystyrene sulfonate (Kayexylate) aspiration (3). Since then sporadic cases of pneumonitis, or bronchitis associated with aspiration of this substance have been reported incidentally in autopsy findings, and pathological specimens (4). Polystyrene sulfate aspiration was not directly attributed to immediate morbidity in any of these patients (4–6). Sodium polystyrene sulfonate is a cation-exchange resin that is suspended in a solution and given orally or by retention enema for the treatment of hyperkalemia in patients with renal insufficiency (7). A systematic review documented that polystyrene crystal deposition can lead to significant colitis in some patients (8). We report a case of severe acute respiratory distress syndrome (ARDS) that occurred as a direct result of sodium polystyrene sulfonate aspiration in an elderly Letters
Case Report An 89-year-old woman was hospitalized for worsening mental status, progressive weakness, and lethargy of 10 days’ duration. One week before admission, she was treated with ciprofloxacin for a urinary tract infection. She had a history of chronic obstructive pulmonary disease, coronary artery disease, and mild dementia. Her medical treatment included long-term use of supplemental oxygen administered via nasal cannula at a rate of 5 L/minute. At the time of admission, her blood pressure was 114/52 mm Hg; heart rate, 110 beats/minute; temperature, 37.18 C; respiratory rate, 28 breaths/minute. Her arterial oxygen saturation (as measured by pulse oximetry; SpO2) was 94% while she breathed oxygen at 5 L/minute. She appeared dehydrated and was somnolent. Auscultation of the lungs revealed decreased air entry in basilar lung fields bilaterally. Her physical examination was otherwise unremarkable. Laboratory analysis showed a white blood cell count of 22,000 cells/mm3; sodium, 993
LETTERS
Figure 1. ( A) Chest radiograph on presentation. (B) Aspiration and early development of bilateral infiltrates suggestive of acute respiratory distress syndrome.
The woman was sedated and paralyzed with cisatracurium and positive end-expiratory pressure was titrated incrementally up to 20 cm H2O. Despite these changes, the oxygen saturation remained low at 80–85%, and the plateau pressures remained above 35 cm H2O. Because of her age, and rapidly deteriorating hemodynamics, prone positioning, extracorporeal membrane oxygenation, and other salvage therapies were not offered. The patient developed refractory hypoxemia with multiorgan failure and refractory shock. The patient was transitioned to do-notresuscitate/comfort care (DNR-CC). She died shortly thereafter. On autopsy numerous foci of intraalveolar, large purple polygonal crystals, consistent with sodium polystyrene sulfonate aspiration were seen in all lung lobes and in the alveolar spaces of the patient’s lungs (Figure 2). These autopsy findings are similar to previous descriptions of sodium polystyrene sulfonate aspiration in the literature (9).
Discussion We report the first case in the English language literature of severe ARDS associated with aspiration of sodium polystyrene
4C/FPO
153 mmol/L; potassium, 6.9 mmol/L; blood urea nitrogen, 69 mg/dl; and creatinine, 1.93 mg/dl. A chest radiograph obtained at the time of admission showed no significant abnormalities (Figure 1A). Because of her elevated potassium, 30 g of sodium polystyrene sulfonate was administered orally. The patient vomited shortly after administration of the medication. She soon developed acute respiratory distress associated with severe hypoxemia. As a result of profound hypoxemia, she went into cardiac arrest with pulseless electrical activity. She received cardiopulmonary resuscitation for 20 minutes with a return of spontaneous circulation. The patient was intubated and transferred to the medical intensive care for further management. Her postintubation chest radiograph revealed extensive bilateral pulmonary infiltrates with new dense consolidation in the right upper lobe (Figure 1B). An arterial blood gas analysis performed while she breathed 100% oxygen revealed pH 7.07, PaCO2 94 mm Hg, and PaO2 67 mm Hg. The ratio of PaO2 to FIO2 (fraction of inspired oxygen) was 67. She was placed on volume-controlled ventilation with low tidal volumes (6 cm3/kg). Her lung compliance was 10 ml/cm H2O. Plateau pressures were as high as 40 cm H2O.
Figure 2. (A) Sodium polystyrene sulfonate (SPS) crystals and extensive alveolar damage. (B) Classic SPS polygonal crystals.
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AnnalsATS Volume 11 Number 6 | July 2014
LETTERS sulfonate. Previously reported episodes were reported as incidental findings on autopsy in patients with other acute illnesses such as bronchopneumonia and inhalational pneumonitis, without a temporal relationship to immediate polystyrene sulfonate administration (4–6). Haupt and Hutchins showed in an animal model that polystyrene sulfonate aspiration is accompanied by florid polymorphonuclear pulmonary infiltrates. These findings suggest that this resin can cause direct lung injury (10). As polystyrene sulfonate has been shown to be associated with alveolar injury in animal models, caution should be exercised when this medication is administered to patients at high risk for aspiration and ARDS. Our patient had a lung injury prediction score (LIPS) of 10 (11). After she aspirated, her respiratory status deteriorated over 2–4 hours and she developed refractory hypoxemia. The acute lung injury associated with extensive deposition of polystyrene sulfonate crystals in the alveoli, and subsequent changes to alveolar surfactant, could explain the sudden onset of this refractory hypoxemia. This has been described in detail in ARDS associated with other types of direct lung injuries (12). We acknowledge that lung injury is associated with a complex inflammatory response, and perhaps multiple insults are responsible for the development of ARDS in these patients (13). However, the extensive damage to the alveolar architecture found in close association with foci of polystyrene crystals at autopsy suggests that toxic effects of the aspirated cationic exchange resin either caused or substantially aggravated multiorgan dysfunction in this elderly patient with multiple comorbidities. Settings for mechanical ventilation of such patients should not necessarily differ from those recommended for ARDS associated with other causes: low tidal volume and open lung ventilation with supportive care should be provided to these patients (14). In patients who are hemodynamically stable and adequately oxygenated, bronchoscopy might be attempted to remove some of the crystals. The fulminant course of disease in our patient precluded any such therapeutic intervention. Our case highlights that in elderly debilitated patients with altered sensorium, aspiration of commonly prescribed drugs such as sodium polystyrene sulfonate can sometimes lead to devastating and even life-threatening effects. In these patients routes other than oral administration or alternative therapy should be considered. In our opinion all pulmonologists and intensivists should be cognizant of the consequence of accidental aspiration of sodium polystyrene sulfonate. Author disclosures are available with the text of this letter at www.atsjournals.org.
Letters
Acknowledgment: This work was performed in the Medical Intensive Care Unit, Cleveland Clinic Foundation, Cleveland, Ohio. Abhijit Duggal, M.D., M.P.H. Shameen Salam, M.D. Atul Mehta, M.D. Respiratory Institute, Cleveland Clinic Foundation Cleveland, Ohio
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