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Acute Renal Failure after Ingestion of Guaifenesin and Dextromethorphan
The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–4, 2014 Copyright Ó 2014 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2014.01.022
Selected Topics: Toxicology
ACUTE RENAL FAILURE AFTER INGESTION OF GUAIFENESIN AND DEXTROMETHORPHAN Evan Small, MD, PHD and Benjamin J. Sandefur, MD Department of Emergency Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota Reprint Address: Benjamin J. Sandefur, MD, Department of Emergency Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905
, Abstract—Background: Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. Objective: We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. Case Report: The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. Conclusions: This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Ó 2014 Elsevier Inc.
resulting in ureteral obstruction and acute renal failure (2–6). Of drug-induced stones reported to date, approximately 35% are thought to be related to guaifenesin, a common nonprescription medication (7). Abuse of nonprescription medications such as dextromethorphan, which is often found in guaifenesin-containing preparations, is known to be increasing among United States (US) youth and young adults (8). CASE REPORT A 22-year-old man presented to the emergency department (ED) with flank pain and hematuria. The patient’s pain began several hours prior and was sharp in nature and bilateral with radiation to the groin and testicles. There was associated hematuria and dysuria, as well as decreased urination after the onset of pain. He denied fevers, chills, nausea, vomiting, or diarrhea. He had no significant medical history. There was neither personal history nor known family history of kidney stones. Upon review of systems, the patient reported taking 10 tablets of MucinexÒ DM (Reckitt Benckiser, Parsippany, NJ), a nonprescription medication containing guaifenesin and dextromethorphan, 1 day before onset of pain. He stated that he ingested the medication recreationally, to dull the pain of a recent break up with his significant other. The patient denied suicidal ideation, stating that his intent was to ‘‘get high.’’ Although the patient had a history of alcohol dependence, he specifically denied prior use of MucinexÒ DM, guaifenesin, or
, Keywords—guaifenesin; dextromethorphan; ureteral obstruction; renal failure; ureteral calculi/medication induced
INTRODUCTION Ureteral stones are frequently encountered in emergency medicine clinical practice. Drug-induced renal stones are believed to comprise approximately 1%–2% of all nephroliths (1). Although uncommon, renally excreted pharmaceuticals with poor solubility in urine have the potential to precipitate in the renal collecting system,
RECEIVED: 3 February 2013; FINAL SUBMISSION RECEIVED: 31 October 2013; ACCEPTED: 30 January 2014 1
2
dextromethorphan-containing medications. He reported that a friend had tried MucinexÒ DM once before and had found it to be ‘‘a pleasant rush.’’ He endorsed sobriety from alcohol for 2 months, however, he continued to occasionally smoke marijuana. He denied other illicit drug use or abuse of pharmaceutical medications. In the community ED, the patient was afebrile, with a heart rate of 90 beats/min and a blood pressure of 150/78 mm Hg. He did not appear intoxicated. A bladder scan demonstrated only 15 mL of urine in the bladder. The serum creatinine was found to be elevated at 1.52 mg/ dL. A computed tomography (CT) scan of the abdomen and pelvis was performed. This reportedly revealed evidence of bilateral obstructing ureteral stones and stranding along the distal ureters. He was given 1.5 mg lorazepam, 4 mg morphine for pain, and a 1-L bolus of 0.9% normal saline. He was transferred to a tertiary care center for further management. Upon arrival to the referral facility, the patient reported ongoing bilateral flank pain, which he rated as a 5 on a 10-point pain scale. He was afebrile with a temperature of 36.7 C (98.1 F). The blood pressure fluctuated between 146/82 and 206/99 mm Hg, and the heart rate was 85 beats/min. He was tachypneic with a respiratory rate of 20 breaths/min, and the oxygen saturation was 96%–98% on room air. Lungs were clear to auscultation bilaterally. His cardiac examination revealed a regular rate and rhythm, without murmurs, rubs, or gallops. The abdomen was soft and nondistended, with mild tenderness to palpation in bilateral lower abdominal quadrants. He endorsed mild bilateral costovertebral angle tenderness. Genitourinary examination revealed descended nontender testicles bilaterally and no evidence of inguinal hernias. Repeat serum chemistries and a complete blood count were obtained. The serum creatinine was found to be 2.5 mg/dL, indicating progressive kidney injury. The white blood cell count was elevated at 21.1 109 cells/ L. The urine was grossly bloody in appearance. The urine Gram stain was negative, and microscopy revealed >100 erythrocytes and >100 leukocytes. Urine toxicology was not obtained. A serum sample was negative for acetaminophen and salicylates. He was given 4 mg i.v. ondansetron and a 1 L bolus of 0.9% normal saline. He was offered 1 mg of i.v. hydromorphone for pain; however, he refused further analgesia. As the CT images obtained at the referring facility were not available, a repeat CT of the abdomen and pelvis without contrast was performed. This demonstrated hyperdense material (10.7 Hounsfield units) present within the distal aspects of both ureters occupying 3 to 4 cm segments proximal to the ureterovesical junction (Figure 1). The radiographic differential diagnosis was noted to include fragmented stone material or clotted blood. The
E. Small and B. J. Sandefur
Figure 1. Computed tomography scan of the abdomen and pelvis without i.v. contrast demonstrating hyperdense material in the distal aspects of both ureters (denoted by arrows).
material was not the expected density of calciumcontaining stones, and there was no stone-like mass in the ureters or kidneys. There was marked bilateral hydroureteronephrosis, perinephric edema, and fluid, consistent with acute obstruction (Figure 2). A urology consultation was obtained, and antibiotic administration was recommended. The patient was taken to the operating room for emergent cystoscopy, bilateral retrograde pyelograms, and decompression of the bilateral collecting systems with stent placement. During the procedure, rigid cystourethroscopy revealed debris of unknown etiology within the bladder. Retrograde pyelograms revealed filling defects in the distal ureters bilaterally with moderate proximal hydroureteronephrosis. Further debris was noted in the distal collecting system bilaterally. No filling defects were observed in the upper tracts of the collecting systems. Bilateral ureteral stents were placed into the renal pelvises under fluoroscopy. The patient was admitted to the hospital in stable condition. Specimens of the debris from the ureteral and bladder aspirates were sent for laboratory analysis. The debris was analyzed by Fourier transform infrared spectroscopy, compared with a library of stone metabolites, and was found to contain predominantly guaifenesin metabolites. Although it is possible that other compounds were present in the sample, they comprised <10% of the sample.
Drug-Induced Acute Renal Failure
Figure 2. Computed tomography scan of the abdomen and pelvis without i.v. contrast demonstrating bilateral hydroureteronephrosis (denoted by asterisks).
Postoperatively, a psychiatric consultation was obtained. It was believed that further inpatient psychiatric care was unnecessary given that the nature of the ingestion was recreational, with no self-harmful intent. On postoperative day 1, the serum creatinine had decreased to 1.2 mg/dL. The patient’s pain was controlled with oral oxycodone, and he was discharged with instructions to follow-up with urology in 4 weeks for stent removal. The patient’s stents were removed without difficulty after 4 weeks. At that time, the patient felt well, and his affect was noted to be pleasant and calm. He was scheduled to have a re-evaluation of his creatinine 1 week later and to undergo an excretory urogram; however, he was subsequently lost to follow-up. DISCUSSION Guaifenesin is a common expectorant medication often used in nonprescription preparations, frequently in combination with antihistamines, antitussives, and decongestants (7,9). The potential for abuse of guaifenesincontaining preparations, specifically those formulated with ephedra or pseudoephedrine, has been well documented (7,10–13). Dextromethorphan is a nonprescription antitussive agent with hallucinogenic properties and known abuse potential, especially among male
3
adolescents (8). These products are present in a combined preparation in several over-the-counter medications, including MucinexÒ DM (Reckitt Benckiser), among others. The patient reportedly ingested 10 tablets of MucinexÒ DM, although it is unknown if he took the regular-strength or maximum-strength preparation, which contain guaifenesin 600 mg/dextromethorphan 30 mg and guaifenesin 1200 mg/dextromethorphan 60 mg, respectively. To the authors’ knowledge, this is the first report of bilateral ureteral obstruction, oliguria, and acute renal failure secondary to an isolated ingestion of guaifenesin and dextromethorphan. Drug-induced nephrolithiasis represents 1%–2% of all renal calculi (1,14). Medications inducing nephrolithiasis can be divided into two groups, based on the mechanism of stone formation (14). The first group consists of drugs that have a high urinary excretion and relatively poor solubility. These medications are prone to crystallization in the urine, leading to nephroliths composed of the drug or drug metabolite. Medications that have been reported to induce nephrolithiasis in this manner include triamterene, sulfonamides, quinolone antibiotics, guaifenesin, ephedrine, pseudoephedrine, and the human immunodeficiency virus protease indinavir (1,5,7,10,11,14–16).The second group consists of medications altering metabolic processes, namely those involving calcium or purine metabolism, which lead to stone formation (1). This category includes loop diuretics, calcium and vitamin D supplements, corticosteroids, and carbonic anhydrase inhibitors (1,15). Guaifenesin-induced nephrolithiasis was first reported in 1999 (10,11). A majority of the patients reported taking nonprescription combined preparations of guaifenesin and ephedrine chronically and in excess, presumably to achieve the stimulant effect that accompanies ephedrine abuse. A guaifenesin metabolite, b-2-methoxyphenoxy-lactic acid, was identified as the predominant stone component. Smaller concentrations of ephedrine and ephedrine metabolite were present (10,11). Subsequently, several case reports of guaifenesin-induced nephrolithiasis, in combination with ephedrine and pseudoephedrine, and all in the setting of chronic abuse, have been published (12,13,17,18). It has been estimated that 35% of urinary stones related to pharmaceutical metabolites, representing approximately 0.1% of all urinary stones, are related to guaifenesin (7). Radiographically, guaifenesin-induced stones mimic uric acid nephrolithiasis (12). The stones are radiolucent on abdominal x-ray study, but are readily demonstrated on CT imaging (10–12,18). Treatment options described in the literature include expectant management for small stones, urinary alkalinization, ureteroscopy and basket extraction, ureteral stent placement, and extracorporeal shockwave lithotripsy (7,10,13,17,19).
4
E. Small and B. J. Sandefur
To the authors’ knowledge, this is the first reported case of bilateral ureteral obstruction and acute renal failure in the setting of an isolated guaifenesin and dextromethorphan ingestion. The ureteral precipitate found on ureteroscopy did not appear to represent a well-formed stone, suggesting that precipitation of drug metabolites was responsible for acute ureteral obstruction, oliguria, and acute renal failure. Although the current literature suggests that the majority of individuals found to have guaifenesininduced nephrolithiasis have a history of long-standing abuse of nonprescription medications, this case highlights the potential risk of acute renal failure with an isolated ingestion. Other medications that have the potential for urinary precipitation, such as sulfonamides, or to potentiate renal hemorrhage, such as anticoagulant or thrombolytic therapy, have been reported to cause acute bilateral ureteral obstruction and renal failure (2–6). Regardless of etiology, patients presenting with acute renal failure secondary to a postobstructive process require urgent urologic consultation. CONCLUSIONS Guaifenesin-induced nephrolithiasis has been previously described in patients chronically consuming large amounts of guaifenesin-containing medication. Although not previously described, a case of guaifenesin-induced bilateral ureteral obstruction and postobstructive renal failure in the setting of acute guaifenesin and dextromethorphan overdose is presented.
REFERENCES 1. Cutrell JB, Reilly RF. Miscellaneous stone types. Clin Rev Bone Miner Metabol 2011;9:229–40.
2. Allinson J, Topping W, Edwards SG, Miller RF. Sulphadiazineinduced obstructive renal failure complicating treatment of HIVassociated toxoplasmosis. Int J STD AIDS 2012;23:210–2. 3. Higenbottam T, Ogg CS, Saxton HM. Acute renal failure from the use of acetazolamide (Diamox). Postgrad Med J 1978;54:127–8. 4. Nade S. Acute urinary suppression presumed due to bilateral ureteric obstruction by blood clot. An unusual feature of anticoagulant therapy. Med J Aust 1972;1:378–80. 5. Sooriyaarachchi GS, Hogan TF. Renal complications during sulfonamide therapy for systemic nocardiosis. Wis Med J 1978;77: S15–8. 6. Toupin LR, Blanchard DG. Acute anuric renal failure: a complication of combined thrombolytic and antithrombotic therapy. Int J Cardiol 1993;40:283–5. 7. Bennett S, Hoffman N, Monga M. Ephedrine- and guaifenesininduced nephrolithiasis. J Altern Complement Med 2004;10:967–9. 8. Wilson MD, Ferguson RW, Mazer ME, Litovitz TL. Monitoring trends in dextromethorphan abuse using the National Poison Data System: 2000 2010. Clin Toxicol 2011;49:409–15. 9. Wogoman H, Steinberg M, Jenkins AJ. Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine. Am J Forensic Med Pathol 1999;20:199–202. 10. Assimos DG, Langenstroer P, Leinbach RF, Mandel NS, Stern JM, Holmes RP. Guaifenesin- and ephedrine-induced stones. J Endourol 1999;13:665–7. 11. Pickens CL, Milliron AR, Fussner AL, et al. Abuse of guaifenesincontaining medications generates and excess of a carboxylate salt of beta-(2-methoxyphenoxy)-lactic acid, a guaifenesin metabolite, and results in urolithiasis. Urology 1999;54:23–7. 12. Song GY, Lockhart ME, Smith JK, Burns JR, Kenney PJ. Pseudoephedrine and guaifenesin urolithiasis: Widening the differential diagnosis of radiolucent calculi on abdominal radiograph. Abdom Imag 2005;30:644–6. 13. Whelan C, Schwartz BF. Bilateral guaifenesin ureteral calculi. Urology 2004;63. 175x–xi. 14. Daudon M, Jungers P. Drug-induced renal calculi: epidemiology, prevention and management. Drugs 2004;64:245–75. 15. Matlaga BR, Assimos DG. Urologic manifestations of nonurologic disease urolithiasis. Urol Clin N Am 2003;30:91–9. 16. Smith CL, Gemar SK, Lewis MJ. Pseudoephedrine urolithiasis associated with acute renal failure. Nephrol Dial Transplant 2004; 19:263–4. 17. Hoffman N, McGee SM, Hulbert JC. Resolution of ephedrine stones with dissolution therapy. Urology 2003;61:1035. 18. Shah N. Not quite the rolling stones. J Hosp Med 2012;7:S242. 19. Nguyen TT, Fallon B, Winfield HN. Spontaneous dissolution of a guaifenesin stone. Can J Urol 2005;12:2769–71.
http://dx.doi.org/10.1016/j.jemermed.2014.01.022
Selected Topics: Toxicology
ACUTE RENAL FAILURE AFTER INGESTION OF GUAIFENESIN AND DEXTROMETHORPHAN Evan Small, MD, PHD and Benjamin J. Sandefur, MD Department of Emergency Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota Reprint Address: Benjamin J. Sandefur, MD, Department of Emergency Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905
, Abstract—Background: Guaifenesin is a common nonprescription medication that has been implicated in drug-induced nephrolithiasis. Dextromethorphan, a nonprescription antitussive found in some guaifenesin-containing preparations, is increasingly recognized as a substance of abuse by many youth and young adults. Renally excreted medications known to have poor solubility in urine have the potential to precipitate when ingested in large quantity, leading to acute obstruction of the ureters and renal failure. Objective: We describe the case of a 22-year-old male who developed severe bilateral flank pain, hematuria, and oliguria after an isolated recreational ingestion of guaifenesin and dextromethorphan. Case Report: The patient was found to have bilateral ureteral obstruction and acute renal failure, suspected to be secondary to precipitation of medication metabolites in the urine. Conclusions: This case highlights the potential for acute renal failure secondary to guaifenesin and dextromethorphan abuse. Ó 2014 Elsevier Inc.
resulting in ureteral obstruction and acute renal failure (2–6). Of drug-induced stones reported to date, approximately 35% are thought to be related to guaifenesin, a common nonprescription medication (7). Abuse of nonprescription medications such as dextromethorphan, which is often found in guaifenesin-containing preparations, is known to be increasing among United States (US) youth and young adults (8). CASE REPORT A 22-year-old man presented to the emergency department (ED) with flank pain and hematuria. The patient’s pain began several hours prior and was sharp in nature and bilateral with radiation to the groin and testicles. There was associated hematuria and dysuria, as well as decreased urination after the onset of pain. He denied fevers, chills, nausea, vomiting, or diarrhea. He had no significant medical history. There was neither personal history nor known family history of kidney stones. Upon review of systems, the patient reported taking 10 tablets of MucinexÒ DM (Reckitt Benckiser, Parsippany, NJ), a nonprescription medication containing guaifenesin and dextromethorphan, 1 day before onset of pain. He stated that he ingested the medication recreationally, to dull the pain of a recent break up with his significant other. The patient denied suicidal ideation, stating that his intent was to ‘‘get high.’’ Although the patient had a history of alcohol dependence, he specifically denied prior use of MucinexÒ DM, guaifenesin, or
, Keywords—guaifenesin; dextromethorphan; ureteral obstruction; renal failure; ureteral calculi/medication induced
INTRODUCTION Ureteral stones are frequently encountered in emergency medicine clinical practice. Drug-induced renal stones are believed to comprise approximately 1%–2% of all nephroliths (1). Although uncommon, renally excreted pharmaceuticals with poor solubility in urine have the potential to precipitate in the renal collecting system,
RECEIVED: 3 February 2013; FINAL SUBMISSION RECEIVED: 31 October 2013; ACCEPTED: 30 January 2014 1
2
dextromethorphan-containing medications. He reported that a friend had tried MucinexÒ DM once before and had found it to be ‘‘a pleasant rush.’’ He endorsed sobriety from alcohol for 2 months, however, he continued to occasionally smoke marijuana. He denied other illicit drug use or abuse of pharmaceutical medications. In the community ED, the patient was afebrile, with a heart rate of 90 beats/min and a blood pressure of 150/78 mm Hg. He did not appear intoxicated. A bladder scan demonstrated only 15 mL of urine in the bladder. The serum creatinine was found to be elevated at 1.52 mg/ dL. A computed tomography (CT) scan of the abdomen and pelvis was performed. This reportedly revealed evidence of bilateral obstructing ureteral stones and stranding along the distal ureters. He was given 1.5 mg lorazepam, 4 mg morphine for pain, and a 1-L bolus of 0.9% normal saline. He was transferred to a tertiary care center for further management. Upon arrival to the referral facility, the patient reported ongoing bilateral flank pain, which he rated as a 5 on a 10-point pain scale. He was afebrile with a temperature of 36.7 C (98.1 F). The blood pressure fluctuated between 146/82 and 206/99 mm Hg, and the heart rate was 85 beats/min. He was tachypneic with a respiratory rate of 20 breaths/min, and the oxygen saturation was 96%–98% on room air. Lungs were clear to auscultation bilaterally. His cardiac examination revealed a regular rate and rhythm, without murmurs, rubs, or gallops. The abdomen was soft and nondistended, with mild tenderness to palpation in bilateral lower abdominal quadrants. He endorsed mild bilateral costovertebral angle tenderness. Genitourinary examination revealed descended nontender testicles bilaterally and no evidence of inguinal hernias. Repeat serum chemistries and a complete blood count were obtained. The serum creatinine was found to be 2.5 mg/dL, indicating progressive kidney injury. The white blood cell count was elevated at 21.1 109 cells/ L. The urine was grossly bloody in appearance. The urine Gram stain was negative, and microscopy revealed >100 erythrocytes and >100 leukocytes. Urine toxicology was not obtained. A serum sample was negative for acetaminophen and salicylates. He was given 4 mg i.v. ondansetron and a 1 L bolus of 0.9% normal saline. He was offered 1 mg of i.v. hydromorphone for pain; however, he refused further analgesia. As the CT images obtained at the referring facility were not available, a repeat CT of the abdomen and pelvis without contrast was performed. This demonstrated hyperdense material (10.7 Hounsfield units) present within the distal aspects of both ureters occupying 3 to 4 cm segments proximal to the ureterovesical junction (Figure 1). The radiographic differential diagnosis was noted to include fragmented stone material or clotted blood. The
E. Small and B. J. Sandefur
Figure 1. Computed tomography scan of the abdomen and pelvis without i.v. contrast demonstrating hyperdense material in the distal aspects of both ureters (denoted by arrows).
material was not the expected density of calciumcontaining stones, and there was no stone-like mass in the ureters or kidneys. There was marked bilateral hydroureteronephrosis, perinephric edema, and fluid, consistent with acute obstruction (Figure 2). A urology consultation was obtained, and antibiotic administration was recommended. The patient was taken to the operating room for emergent cystoscopy, bilateral retrograde pyelograms, and decompression of the bilateral collecting systems with stent placement. During the procedure, rigid cystourethroscopy revealed debris of unknown etiology within the bladder. Retrograde pyelograms revealed filling defects in the distal ureters bilaterally with moderate proximal hydroureteronephrosis. Further debris was noted in the distal collecting system bilaterally. No filling defects were observed in the upper tracts of the collecting systems. Bilateral ureteral stents were placed into the renal pelvises under fluoroscopy. The patient was admitted to the hospital in stable condition. Specimens of the debris from the ureteral and bladder aspirates were sent for laboratory analysis. The debris was analyzed by Fourier transform infrared spectroscopy, compared with a library of stone metabolites, and was found to contain predominantly guaifenesin metabolites. Although it is possible that other compounds were present in the sample, they comprised <10% of the sample.
Drug-Induced Acute Renal Failure
Figure 2. Computed tomography scan of the abdomen and pelvis without i.v. contrast demonstrating bilateral hydroureteronephrosis (denoted by asterisks).
Postoperatively, a psychiatric consultation was obtained. It was believed that further inpatient psychiatric care was unnecessary given that the nature of the ingestion was recreational, with no self-harmful intent. On postoperative day 1, the serum creatinine had decreased to 1.2 mg/dL. The patient’s pain was controlled with oral oxycodone, and he was discharged with instructions to follow-up with urology in 4 weeks for stent removal. The patient’s stents were removed without difficulty after 4 weeks. At that time, the patient felt well, and his affect was noted to be pleasant and calm. He was scheduled to have a re-evaluation of his creatinine 1 week later and to undergo an excretory urogram; however, he was subsequently lost to follow-up. DISCUSSION Guaifenesin is a common expectorant medication often used in nonprescription preparations, frequently in combination with antihistamines, antitussives, and decongestants (7,9). The potential for abuse of guaifenesincontaining preparations, specifically those formulated with ephedra or pseudoephedrine, has been well documented (7,10–13). Dextromethorphan is a nonprescription antitussive agent with hallucinogenic properties and known abuse potential, especially among male
3
adolescents (8). These products are present in a combined preparation in several over-the-counter medications, including MucinexÒ DM (Reckitt Benckiser), among others. The patient reportedly ingested 10 tablets of MucinexÒ DM, although it is unknown if he took the regular-strength or maximum-strength preparation, which contain guaifenesin 600 mg/dextromethorphan 30 mg and guaifenesin 1200 mg/dextromethorphan 60 mg, respectively. To the authors’ knowledge, this is the first report of bilateral ureteral obstruction, oliguria, and acute renal failure secondary to an isolated ingestion of guaifenesin and dextromethorphan. Drug-induced nephrolithiasis represents 1%–2% of all renal calculi (1,14). Medications inducing nephrolithiasis can be divided into two groups, based on the mechanism of stone formation (14). The first group consists of drugs that have a high urinary excretion and relatively poor solubility. These medications are prone to crystallization in the urine, leading to nephroliths composed of the drug or drug metabolite. Medications that have been reported to induce nephrolithiasis in this manner include triamterene, sulfonamides, quinolone antibiotics, guaifenesin, ephedrine, pseudoephedrine, and the human immunodeficiency virus protease indinavir (1,5,7,10,11,14–16).The second group consists of medications altering metabolic processes, namely those involving calcium or purine metabolism, which lead to stone formation (1). This category includes loop diuretics, calcium and vitamin D supplements, corticosteroids, and carbonic anhydrase inhibitors (1,15). Guaifenesin-induced nephrolithiasis was first reported in 1999 (10,11). A majority of the patients reported taking nonprescription combined preparations of guaifenesin and ephedrine chronically and in excess, presumably to achieve the stimulant effect that accompanies ephedrine abuse. A guaifenesin metabolite, b-2-methoxyphenoxy-lactic acid, was identified as the predominant stone component. Smaller concentrations of ephedrine and ephedrine metabolite were present (10,11). Subsequently, several case reports of guaifenesin-induced nephrolithiasis, in combination with ephedrine and pseudoephedrine, and all in the setting of chronic abuse, have been published (12,13,17,18). It has been estimated that 35% of urinary stones related to pharmaceutical metabolites, representing approximately 0.1% of all urinary stones, are related to guaifenesin (7). Radiographically, guaifenesin-induced stones mimic uric acid nephrolithiasis (12). The stones are radiolucent on abdominal x-ray study, but are readily demonstrated on CT imaging (10–12,18). Treatment options described in the literature include expectant management for small stones, urinary alkalinization, ureteroscopy and basket extraction, ureteral stent placement, and extracorporeal shockwave lithotripsy (7,10,13,17,19).
4
E. Small and B. J. Sandefur
To the authors’ knowledge, this is the first reported case of bilateral ureteral obstruction and acute renal failure in the setting of an isolated guaifenesin and dextromethorphan ingestion. The ureteral precipitate found on ureteroscopy did not appear to represent a well-formed stone, suggesting that precipitation of drug metabolites was responsible for acute ureteral obstruction, oliguria, and acute renal failure. Although the current literature suggests that the majority of individuals found to have guaifenesininduced nephrolithiasis have a history of long-standing abuse of nonprescription medications, this case highlights the potential risk of acute renal failure with an isolated ingestion. Other medications that have the potential for urinary precipitation, such as sulfonamides, or to potentiate renal hemorrhage, such as anticoagulant or thrombolytic therapy, have been reported to cause acute bilateral ureteral obstruction and renal failure (2–6). Regardless of etiology, patients presenting with acute renal failure secondary to a postobstructive process require urgent urologic consultation. CONCLUSIONS Guaifenesin-induced nephrolithiasis has been previously described in patients chronically consuming large amounts of guaifenesin-containing medication. Although not previously described, a case of guaifenesin-induced bilateral ureteral obstruction and postobstructive renal failure in the setting of acute guaifenesin and dextromethorphan overdose is presented.
REFERENCES 1. Cutrell JB, Reilly RF. Miscellaneous stone types. Clin Rev Bone Miner Metabol 2011;9:229–40.
2. Allinson J, Topping W, Edwards SG, Miller RF. Sulphadiazineinduced obstructive renal failure complicating treatment of HIVassociated toxoplasmosis. Int J STD AIDS 2012;23:210–2. 3. Higenbottam T, Ogg CS, Saxton HM. Acute renal failure from the use of acetazolamide (Diamox). Postgrad Med J 1978;54:127–8. 4. Nade S. Acute urinary suppression presumed due to bilateral ureteric obstruction by blood clot. An unusual feature of anticoagulant therapy. Med J Aust 1972;1:378–80. 5. Sooriyaarachchi GS, Hogan TF. Renal complications during sulfonamide therapy for systemic nocardiosis. Wis Med J 1978;77: S15–8. 6. Toupin LR, Blanchard DG. Acute anuric renal failure: a complication of combined thrombolytic and antithrombotic therapy. Int J Cardiol 1993;40:283–5. 7. Bennett S, Hoffman N, Monga M. Ephedrine- and guaifenesininduced nephrolithiasis. J Altern Complement Med 2004;10:967–9. 8. Wilson MD, Ferguson RW, Mazer ME, Litovitz TL. Monitoring trends in dextromethorphan abuse using the National Poison Data System: 2000 2010. Clin Toxicol 2011;49:409–15. 9. Wogoman H, Steinberg M, Jenkins AJ. Acute intoxication with guaifenesin, diphenhydramine, and chlorpheniramine. Am J Forensic Med Pathol 1999;20:199–202. 10. Assimos DG, Langenstroer P, Leinbach RF, Mandel NS, Stern JM, Holmes RP. Guaifenesin- and ephedrine-induced stones. J Endourol 1999;13:665–7. 11. Pickens CL, Milliron AR, Fussner AL, et al. Abuse of guaifenesincontaining medications generates and excess of a carboxylate salt of beta-(2-methoxyphenoxy)-lactic acid, a guaifenesin metabolite, and results in urolithiasis. Urology 1999;54:23–7. 12. Song GY, Lockhart ME, Smith JK, Burns JR, Kenney PJ. Pseudoephedrine and guaifenesin urolithiasis: Widening the differential diagnosis of radiolucent calculi on abdominal radiograph. Abdom Imag 2005;30:644–6. 13. Whelan C, Schwartz BF. Bilateral guaifenesin ureteral calculi. Urology 2004;63. 175x–xi. 14. Daudon M, Jungers P. Drug-induced renal calculi: epidemiology, prevention and management. Drugs 2004;64:245–75. 15. Matlaga BR, Assimos DG. Urologic manifestations of nonurologic disease urolithiasis. Urol Clin N Am 2003;30:91–9. 16. Smith CL, Gemar SK, Lewis MJ. Pseudoephedrine urolithiasis associated with acute renal failure. Nephrol Dial Transplant 2004; 19:263–4. 17. Hoffman N, McGee SM, Hulbert JC. Resolution of ephedrine stones with dissolution therapy. Urology 2003;61:1035. 18. Shah N. Not quite the rolling stones. J Hosp Med 2012;7:S242. 19. Nguyen TT, Fallon B, Winfield HN. Spontaneous dissolution of a guaifenesin stone. Can J Urol 2005;12:2769–71.