EM:RAP COMMENTARY
Why Does Your Dandruff Smell Like Urine? Pablo Aguilera, MD*; Paul Jhun, MD; Aaron Bright, MD; Mel Herbert, MD *Corresponding Author. E-mail: [email protected], Twitter: @PabloEMDR.
0196-0644/$-see front matter Copyright © 2015 by the American College of Emergency Physicians. http://dx.doi.org/10.1016/j.annemergmed.2015.01.017
SEE RELATED ARTICLE, P. 341. [Ann Emerg Med. 2015;65:342-344.] Editor’s note: Annals has partnered with EM:RAP, enabling our readers without subscriptions to the EM:RAP service to enjoy their commentary on Annals publications. This article did not undergo peer review and may not reflect the view and opinions of the editorial board of Annals of Emergency Medicine.
ANNALS CASE A 26-year-old man with hypertension and end-stage renal disease (ESRD) presents to the emergency department (ED) with worsening shortness of breath developing during the past 2 weeks. He is visibly dyspneic and has difficulty speaking. He is alert but is slow to respond to questions. He reports that he stopped attending dialysis approximately 3 weeks ago because of fear that the dialysis staff was “stealing” his blood. On physical examination, white flaky material is noted on the patient’s scalp (Figure). The blood urea nitrogen (BUN) level is 249 mg/dL.
DANDRUFF VERSUS URINE CRYSTALS: NOT GOOD EITHER WAY Uremic frost happens when excessive nitrogenous waste products accumulate in sweat, crystallize, and deposit on the skin. Think of your fifth-grade saltwater evaporation experiment separating salt from water, but replace the salt and water with urine and sweat. Yeah, it’s that gross. Uremic frost is an uncommon presentation of patients with chronic renal failure in developed countries because of early dialysis interventions, but it can still be seen among underserved populations and in developing countries as a presenting manifestation of ESRD. To be clear, although the uremic frost itself isn’t life threatening, it is one of those visual “messages from above” that herald such a high underlying azotemia that you will probably have a sick patient in front of you.
LABORATORY CONFIRMS A CRITICALLY HIGH BUN LEVEL. SO WHAT? Although calling up the nephrologist to come in at 1 AM for emergency dialysis may seem straightforward in a patient with an 342 Annals of Emergency Medicine
accompanying serum potassium level of 9.0 mEq/L and a widening QRS on the ECG, we also need to recognize the following 3 organ systems and clinical presentations of uremia that should trigger an immediate conversation with your slumbering nephrologist:
BRAIN, HEART, BLOOD 1. For the altered ESRD patient, remember uremic encephalopathy. 2. For the dyspneic ESRD patient, remember uremic pericardial effusion. 3. For the bleeding ESRD patient, remember uremic platelet dysfunction.
BRAIN: ALTERED MENTAL STATUS? We don’t know which specific toxins are responsible for uremic encephalopathy, but current theories suggest that accumulated uremic toxins are responsible for brain dysfunction.1,2 If left untreated, uremic encephalopathy can progress to death. To make matters more complicated, it presents across a spectrum of both mental and motor disturbances: from mild symptoms, such as lethargy or irritability and asterixis or tremor, to more severe presentations, such as coma and seizures.3 Treatment The patient must begin receiving dialysis. Again, although the exact pathophysiology is unclear, we do know that dialysis resolves uremic encephalopathy. The resolution is not immediate. It usually takes between 1 and 2 days to resolve the clinical symptoms. In most cases, recovery should be complete.3
HEART: SHORT OF BREATH? Granted, the heart of the ESRD patient is already affected in multiple ways, with 10 to 30 times increased mortality because of cardiovascular disease compared with that of the general population.4 Specifically, in the acutely dyspneic ESRD patient, the most common cause of dyspnea is volume overload. That being said, if you see a really high BUN level and a dyspneic ESRD patient not improving with standard therapy, consider uremic pericardial effusion. Believe it or not, renal failure can lead to pericardial effusions in up to 20% of patients!5 The specific pathophysiology of this entity is unknown (sound Volume 65, no. 3 : March 2015
Aguilera et al familiar?) but it usually correlates with the BUN level.6 Clinical presentations can vary from pleuritic chest pain with or without fever to shock when pericardial effusion evolves into cardiac tamponade. The cornerstone for diagnosis is clinical suspicion: if you don’t think it, you can’t diagnose it! As you can imagine, bedside ultrasonography plays an important role in the rapid diagnosis of pericardial effusion. Treatment Unstable patient with large pericardial effusion with diastolic collapse ¼ Emergency pericardiocentesis followed by dialysis Stable patient with pericardial effusion ¼ Dialysis Uremic pericarditis without pericardial effusion ¼ Dialysis Persistent pericarditis pain? Not much information exists in the literature. Nonsteroidal anti-inflammatory drugs do not resolve inflammation or effusions; they actually might worsen the already impaired renal function and affect platelet function. High-dose steroids might be beneficial, but you’ve got to weigh the systemic adverse effects. Colchicine has been shown to diminish recurrences in patients with uremic pericarditis.7,8
EM:RAP Commentary of 3 mg/kg can also be given intranasally.10 Assuming no contraindications, give desmopressin! Packed RBC transfusion. If you dig deep into the recesses of your mind, you may remember that the interaction between platelets and RBCs is important in hemostasis. Correcting the anemia helps facilitate platelet aggregation.15 For the acutely bleeding ESRD patient, some suggest increasing serum hemoglobin to an approximate goal of 10 g/dL.16 Cryoprecipitate. Cryoprecipitate contains von Willebrand factor, but it should be reserved for bleeding ESRD patients resistant to desmopressin and blood transfusions because of the risk of infectious complications. In the acutely bleeding adult ESRD patient, one review recommends administering 10 units of cryoprecipitate intravenously during 30 minutes, with an expected onset of action within 1 hour.10
CASE RESOLUTION The patient began receiving hemodialysis, with improvement of his mental status and volume status. Psychiatric evaluation was obtained.
BLOOD: BLEEDING?
THE BOTTOM LINE
Bleeding ESRD patients can present as a catastrophe to the ED. We don’t know exactly how uremia messes up platelet function (déjà vu), but it does; hence, the diagnosis of uremic platelet dysfunction. What is unique about uremic platelet dysfunction is that bleeding risk does not correlate with the serum BUN or creatinine level.9 As you can imagine, elevated bleeding time is the hallmark of uremic platelet dysfunction, but when’s the last time you performed that test? You just have to consider uremic platelet dysfunction in the bleeding ESRD patient who won’t stop bleeding despite standard intervention and relatively normal serum platelet and coagulation numbers.
Author affiliations: From the Emergency Medicine Program, P. Universidad Católica de Chile, Santiago, Región Metropolitana, Chile (Aguilera); the Department of Emergency Medicine, University of California, San Francisco, CA (Jhun); and the Department of Emergency Medicine, University of Southern California, Los Angeles, CA (Bright, Herbert).
Treatment: Desmopressin, Dialysis, and Maybe Blood Transfusion Dialysis. Intuitively, dialysis makes sense because it removes uremic toxins that may contribute to the underlying platelet dysfunction. Moreover, heparin-free hemodialysis protocols exist, if you were worried about anticoagulation. That being said, the studies looking at the efficacy of dialysis to reverse uremic bleeding, although generally favorable, are old and poorly designed. In the end, dialysis is a generally recommended intervention.10,11 Desmopressin. This is the easiest and fastest way to improve platelet dysfunction in ESRD patients. Desmopressin stimulates the release of von Willebrand factor, which helps platelets work better.12 It has been shown to help more than half of bleeding ESRD patients13,14 and can be given intranasally, intravenously, or subcutaneously. The dose is 0.3 mg/kg in 50 mL of saline solution during 30 minutes intravenously, or by subcutaneous injection. Onset of action is within 1 hour. Alternatively, a dose Volume 65, no. 3 : March 2015
In the ESRD patient with azotemia, remember “brain, heart, blood.” Altered mental status ¼ Remember uremic encephalopathy Dyspnea ¼ Remember uremic pericardial effusion Bleeding ¼ Remember uremic platelet dysfunction
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: Dr. Aguilera reports other from EM:RAP, outside the submitted work. Dr. Jhun reports other from Hippo Education, Inc., outside the submitted work. Dr. Bright reports other from Hippo Education, Inc., outside the submitted work. Dr. Herbert reports other from EM:RAP and Hippo Education, Inc., outside the submitted work. REFERENCES 1. Bucurescu M. Neurological manifestations of uremic encephalopathy. Medscape. Available at: http://emedicine.medscape.com/article/ 1135651-overview. Accessed January 7, 2015. 2. Lohr JW. Uremic encephalopathy. Medscape. Available at: http:// emedicine.medscape.com/article/239191-overview. Accessed January 7, 2015. 3. Baumgaertel MW, Kraemer M, Berlit P. Neurologic complications of acute and chronic renal disease. Handb Clin Neurol. 2014;119: 383-393.
Annals of Emergency Medicine 343
Aguilera et al
EM:RAP Commentary 4. Alfonzo A, Simpson K, Deighan C. Modifications to advanced life support in renal failure. Resuscitation. 2007;73:12-28. 5. Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the task force on the diagnosis and management of pericardial diseases of the European Society of Cardiology. Eur Heart J. 2004;25:587-610. 6. Alpert MA, Ravenscraft MD. Pericardial involvement in end-stage renal disease. Am J Med Sci. 2003;325:228-236. 7. Shabetai R. Corticosteroids for recurrent pericarditis: on the road to evidence-based medicine. Circulation. 2008;118:612. 8. Spaia S, Patsalas S, Agelou A, et al. Managing refractory uraemic pericarditis with colchicine. Nephrol Dial Transplant. 2004;19: 2422. 9. Linthorst GE, Avis HJ, Levi M. Uremic thrombocytopathy is not about urea. J Am Soc Nephrol. 2010;21:753. 10. Hedges SJ, Dehoney SB, Hooper JS, et al. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol. 2007;3:138.
11. Galbusera M, Remuzzi G, Boccardo P. Treatment of bleeding in dialysis patients. Semin Dial. 2009;22:279-286. 12. Gordz S, Mrowietz C, Pindur G, et al. Effect of desmopressin (DDAVP) on platelet membrane glycoprotein expression in patients with von Willebrand’s disease. Clin Hemorheol Microcirc. 2005;32: 83-87. 13. Zeigler ZR, Megaludis A, Fraley DS. Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities in uremia. Am J Hematol. 1992;39:90-95. 14. Mannucci PM, Remuzzi G, Pusineri F, et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983;308:8-12. 15. Livio M, Gotti E, Marchesi D, et al. Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions. Lancet. 1982;2:1013-1015. 16. Berns JS, Coutre S. Platelet dysfunction in uremia. UpToDate. Available at: http://www.uptodate.com/contents/platelet-dysfunction-in-uremia. Accessed January 7, 2015.
CORRECTION In the July 2013 issue, regarding the article by Bobrow et al (“The Influence of Scenario-Based Training and Real-Time Audiovisual Feedback on Out-of-Hospital Cardiopulmonary Resuscitation Quality and Survival From Out-of-Hospital Cardiac Arrest,” pages 47-56) there were two instances in the article that the wrong unit was used. In the Methods of Measurement section and in Table 3, milli-inches should be centi-inches. The authors regret this error.
344 Annals of Emergency Medicine
Volume 65, no. 3 : March 2015
Why Does Your Dandruff Smell Like Urine? Pablo Aguilera, MD*; Paul Jhun, MD; Aaron Bright, MD; Mel Herbert, MD *Corresponding Author. E-mail: [email protected], Twitter: @PabloEMDR.
0196-0644/$-see front matter Copyright © 2015 by the American College of Emergency Physicians. http://dx.doi.org/10.1016/j.annemergmed.2015.01.017
SEE RELATED ARTICLE, P. 341. [Ann Emerg Med. 2015;65:342-344.] Editor’s note: Annals has partnered with EM:RAP, enabling our readers without subscriptions to the EM:RAP service to enjoy their commentary on Annals publications. This article did not undergo peer review and may not reflect the view and opinions of the editorial board of Annals of Emergency Medicine.
ANNALS CASE A 26-year-old man with hypertension and end-stage renal disease (ESRD) presents to the emergency department (ED) with worsening shortness of breath developing during the past 2 weeks. He is visibly dyspneic and has difficulty speaking. He is alert but is slow to respond to questions. He reports that he stopped attending dialysis approximately 3 weeks ago because of fear that the dialysis staff was “stealing” his blood. On physical examination, white flaky material is noted on the patient’s scalp (Figure). The blood urea nitrogen (BUN) level is 249 mg/dL.
DANDRUFF VERSUS URINE CRYSTALS: NOT GOOD EITHER WAY Uremic frost happens when excessive nitrogenous waste products accumulate in sweat, crystallize, and deposit on the skin. Think of your fifth-grade saltwater evaporation experiment separating salt from water, but replace the salt and water with urine and sweat. Yeah, it’s that gross. Uremic frost is an uncommon presentation of patients with chronic renal failure in developed countries because of early dialysis interventions, but it can still be seen among underserved populations and in developing countries as a presenting manifestation of ESRD. To be clear, although the uremic frost itself isn’t life threatening, it is one of those visual “messages from above” that herald such a high underlying azotemia that you will probably have a sick patient in front of you.
LABORATORY CONFIRMS A CRITICALLY HIGH BUN LEVEL. SO WHAT? Although calling up the nephrologist to come in at 1 AM for emergency dialysis may seem straightforward in a patient with an 342 Annals of Emergency Medicine
accompanying serum potassium level of 9.0 mEq/L and a widening QRS on the ECG, we also need to recognize the following 3 organ systems and clinical presentations of uremia that should trigger an immediate conversation with your slumbering nephrologist:
BRAIN, HEART, BLOOD 1. For the altered ESRD patient, remember uremic encephalopathy. 2. For the dyspneic ESRD patient, remember uremic pericardial effusion. 3. For the bleeding ESRD patient, remember uremic platelet dysfunction.
BRAIN: ALTERED MENTAL STATUS? We don’t know which specific toxins are responsible for uremic encephalopathy, but current theories suggest that accumulated uremic toxins are responsible for brain dysfunction.1,2 If left untreated, uremic encephalopathy can progress to death. To make matters more complicated, it presents across a spectrum of both mental and motor disturbances: from mild symptoms, such as lethargy or irritability and asterixis or tremor, to more severe presentations, such as coma and seizures.3 Treatment The patient must begin receiving dialysis. Again, although the exact pathophysiology is unclear, we do know that dialysis resolves uremic encephalopathy. The resolution is not immediate. It usually takes between 1 and 2 days to resolve the clinical symptoms. In most cases, recovery should be complete.3
HEART: SHORT OF BREATH? Granted, the heart of the ESRD patient is already affected in multiple ways, with 10 to 30 times increased mortality because of cardiovascular disease compared with that of the general population.4 Specifically, in the acutely dyspneic ESRD patient, the most common cause of dyspnea is volume overload. That being said, if you see a really high BUN level and a dyspneic ESRD patient not improving with standard therapy, consider uremic pericardial effusion. Believe it or not, renal failure can lead to pericardial effusions in up to 20% of patients!5 The specific pathophysiology of this entity is unknown (sound Volume 65, no. 3 : March 2015
Aguilera et al familiar?) but it usually correlates with the BUN level.6 Clinical presentations can vary from pleuritic chest pain with or without fever to shock when pericardial effusion evolves into cardiac tamponade. The cornerstone for diagnosis is clinical suspicion: if you don’t think it, you can’t diagnose it! As you can imagine, bedside ultrasonography plays an important role in the rapid diagnosis of pericardial effusion. Treatment Unstable patient with large pericardial effusion with diastolic collapse ¼ Emergency pericardiocentesis followed by dialysis Stable patient with pericardial effusion ¼ Dialysis Uremic pericarditis without pericardial effusion ¼ Dialysis Persistent pericarditis pain? Not much information exists in the literature. Nonsteroidal anti-inflammatory drugs do not resolve inflammation or effusions; they actually might worsen the already impaired renal function and affect platelet function. High-dose steroids might be beneficial, but you’ve got to weigh the systemic adverse effects. Colchicine has been shown to diminish recurrences in patients with uremic pericarditis.7,8
EM:RAP Commentary of 3 mg/kg can also be given intranasally.10 Assuming no contraindications, give desmopressin! Packed RBC transfusion. If you dig deep into the recesses of your mind, you may remember that the interaction between platelets and RBCs is important in hemostasis. Correcting the anemia helps facilitate platelet aggregation.15 For the acutely bleeding ESRD patient, some suggest increasing serum hemoglobin to an approximate goal of 10 g/dL.16 Cryoprecipitate. Cryoprecipitate contains von Willebrand factor, but it should be reserved for bleeding ESRD patients resistant to desmopressin and blood transfusions because of the risk of infectious complications. In the acutely bleeding adult ESRD patient, one review recommends administering 10 units of cryoprecipitate intravenously during 30 minutes, with an expected onset of action within 1 hour.10
CASE RESOLUTION The patient began receiving hemodialysis, with improvement of his mental status and volume status. Psychiatric evaluation was obtained.
BLOOD: BLEEDING?
THE BOTTOM LINE
Bleeding ESRD patients can present as a catastrophe to the ED. We don’t know exactly how uremia messes up platelet function (déjà vu), but it does; hence, the diagnosis of uremic platelet dysfunction. What is unique about uremic platelet dysfunction is that bleeding risk does not correlate with the serum BUN or creatinine level.9 As you can imagine, elevated bleeding time is the hallmark of uremic platelet dysfunction, but when’s the last time you performed that test? You just have to consider uremic platelet dysfunction in the bleeding ESRD patient who won’t stop bleeding despite standard intervention and relatively normal serum platelet and coagulation numbers.
Author affiliations: From the Emergency Medicine Program, P. Universidad Católica de Chile, Santiago, Región Metropolitana, Chile (Aguilera); the Department of Emergency Medicine, University of California, San Francisco, CA (Jhun); and the Department of Emergency Medicine, University of Southern California, Los Angeles, CA (Bright, Herbert).
Treatment: Desmopressin, Dialysis, and Maybe Blood Transfusion Dialysis. Intuitively, dialysis makes sense because it removes uremic toxins that may contribute to the underlying platelet dysfunction. Moreover, heparin-free hemodialysis protocols exist, if you were worried about anticoagulation. That being said, the studies looking at the efficacy of dialysis to reverse uremic bleeding, although generally favorable, are old and poorly designed. In the end, dialysis is a generally recommended intervention.10,11 Desmopressin. This is the easiest and fastest way to improve platelet dysfunction in ESRD patients. Desmopressin stimulates the release of von Willebrand factor, which helps platelets work better.12 It has been shown to help more than half of bleeding ESRD patients13,14 and can be given intranasally, intravenously, or subcutaneously. The dose is 0.3 mg/kg in 50 mL of saline solution during 30 minutes intravenously, or by subcutaneous injection. Onset of action is within 1 hour. Alternatively, a dose Volume 65, no. 3 : March 2015
In the ESRD patient with azotemia, remember “brain, heart, blood.” Altered mental status ¼ Remember uremic encephalopathy Dyspnea ¼ Remember uremic pericardial effusion Bleeding ¼ Remember uremic platelet dysfunction
Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). The authors have stated that no such relationships exist and provided the following details: Dr. Aguilera reports other from EM:RAP, outside the submitted work. Dr. Jhun reports other from Hippo Education, Inc., outside the submitted work. Dr. Bright reports other from Hippo Education, Inc., outside the submitted work. Dr. Herbert reports other from EM:RAP and Hippo Education, Inc., outside the submitted work. REFERENCES 1. Bucurescu M. Neurological manifestations of uremic encephalopathy. Medscape. Available at: http://emedicine.medscape.com/article/ 1135651-overview. Accessed January 7, 2015. 2. Lohr JW. Uremic encephalopathy. Medscape. Available at: http:// emedicine.medscape.com/article/239191-overview. Accessed January 7, 2015. 3. Baumgaertel MW, Kraemer M, Berlit P. Neurologic complications of acute and chronic renal disease. Handb Clin Neurol. 2014;119: 383-393.
Annals of Emergency Medicine 343
Aguilera et al
EM:RAP Commentary 4. Alfonzo A, Simpson K, Deighan C. Modifications to advanced life support in renal failure. Resuscitation. 2007;73:12-28. 5. Maisch B, Seferovic PM, Ristic AD, et al. Guidelines on the diagnosis and management of pericardial diseases executive summary: the task force on the diagnosis and management of pericardial diseases of the European Society of Cardiology. Eur Heart J. 2004;25:587-610. 6. Alpert MA, Ravenscraft MD. Pericardial involvement in end-stage renal disease. Am J Med Sci. 2003;325:228-236. 7. Shabetai R. Corticosteroids for recurrent pericarditis: on the road to evidence-based medicine. Circulation. 2008;118:612. 8. Spaia S, Patsalas S, Agelou A, et al. Managing refractory uraemic pericarditis with colchicine. Nephrol Dial Transplant. 2004;19: 2422. 9. Linthorst GE, Avis HJ, Levi M. Uremic thrombocytopathy is not about urea. J Am Soc Nephrol. 2010;21:753. 10. Hedges SJ, Dehoney SB, Hooper JS, et al. Evidence-based treatment recommendations for uremic bleeding. Nat Clin Pract Nephrol. 2007;3:138.
11. Galbusera M, Remuzzi G, Boccardo P. Treatment of bleeding in dialysis patients. Semin Dial. 2009;22:279-286. 12. Gordz S, Mrowietz C, Pindur G, et al. Effect of desmopressin (DDAVP) on platelet membrane glycoprotein expression in patients with von Willebrand’s disease. Clin Hemorheol Microcirc. 2005;32: 83-87. 13. Zeigler ZR, Megaludis A, Fraley DS. Desmopressin (d-DAVP) effects on platelet rheology and von Willebrand factor activities in uremia. Am J Hematol. 1992;39:90-95. 14. Mannucci PM, Remuzzi G, Pusineri F, et al. Deamino-8-D-arginine vasopressin shortens the bleeding time in uremia. N Engl J Med. 1983;308:8-12. 15. Livio M, Gotti E, Marchesi D, et al. Uraemic bleeding: role of anaemia and beneficial effect of red cell transfusions. Lancet. 1982;2:1013-1015. 16. Berns JS, Coutre S. Platelet dysfunction in uremia. UpToDate. Available at: http://www.uptodate.com/contents/platelet-dysfunction-in-uremia. Accessed January 7, 2015.
CORRECTION In the July 2013 issue, regarding the article by Bobrow et al (“The Influence of Scenario-Based Training and Real-Time Audiovisual Feedback on Out-of-Hospital Cardiopulmonary Resuscitation Quality and Survival From Out-of-Hospital Cardiac Arrest,” pages 47-56) there were two instances in the article that the wrong unit was used. In the Methods of Measurement section and in Table 3, milli-inches should be centi-inches. The authors regret this error.
344 Annals of Emergency Medicine
Volume 65, no. 3 : March 2015
