Clinical Toxicology (2014), 52, 231–232 Copyright © 2014 Informa Healthcare USA, Inc. ISSN: 1556-3650 print / 1556-9519 online DOI: 10.3109/15563650.2014.892604
IMAGES
Chronic hematuria and abdominal pain N. J. CONNORS,1 A. GRINO,2 M. G. TUNIK,2 and R. S. HOFFMAN1 1Division
of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA of Emergency Medicine, New York University School of Medicine, New York, NY, USA
Clinical Toxicology Downloaded from informahealthcare.com by University of Laval on 07/10/14 For personal use only.
2Department
An 18-year-old Asian woman with a history of substance abuse presented to the Emergency Department with right-sided abdominal pain and hematuria of several months duration. Physical examination revealed right upper quadrant and suprapubic tenderness. Liver function tests were normal. Urinalysis showed: large blood, 30–50 red blood cells/high-powered field, and no bacteria. She underwent a CT of the abdomen and pelvis following oral and intravenous contrast. Keywords
Common bile duct dilation; Cystitis; Substance abuse
Presentation An 18-year-old Asian woman, 46.3 kg, presented to the Emergency Department (ED) with right-sided abdominal pain and hematuria of several months duration. Prior evaluation of her abdominal pain included an abdominal ultrasound that showed a dilated common bile duct (CBD), magnetic resonance cholangiopancreatography that revealed CBD dilation without evidence of choledocholithiasis, heptaobiliary iminodiacetic acid cholescintigraphy that noted delayed filling of the gall bladder, and an esophagogastroduodenoscopy that showed gastritis. Six days prior to this presentation she was seen in another ED, diagnosed with a urinary tract infection, and prescribed cephalexin, ketorolac, and hydrocodone/ acetaminophen, which she was taking. Her vital signs were as follows: BP, 119/86 mmHg; HR, 78/min; RR, 20/min; temperature, 98.8°F; and oxygen saturation, 100% on room air. Her physical examination was significant for white powder in her hair and tenderness in the right upper quadrant and suprapubic region without rebound or guarding. Liver function tests were normal. Urinalysis showed: large blood; small leukocyte esterase; white blood cells, 10–15/high powered field (HPF); red blood cells, 30–50/HPF; and no bacteria. Urine drug screen for phencyclidine was negative, but was positive for opiates. She underwent a CT of the abdomen and pelvis following oral and intravenous contrast (Fig. 1).
Diagnosis The CT showed marked distension of the gall bladder, a CBD diameter of 8 mm, and signs of inflammation of the Received 12 December 2013; accepted 4 February 2014.
Fig. 1. Coronal image from a CT of the abdomen and pelvis following oral and intravenous contrast showing signs of urinary bladder mucosal inflammation and CBD dilation to 8 mm. No obstructive stones or masses were noted. The kidney and ureters were unremarkable.
Address correspondence to Nicholas J. Connors, Division of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, 455 First Ave, Room 123, New York, NY 10016, USA. E-mail: [email protected]
mucosal surface of the bladder. The kidneys and ureters were normal and no choledocholithiasis was seen on this or subsequent ultrasound imaging. Pathologies in the biliary and 231
Clinical Toxicology Downloaded from informahealthcare.com by University of Laval on 07/10/14 For personal use only.
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urinary tracts are suggestive findings in a substance abuser. During her ED stay a plastic bag of white powder fell from the patient’s purse and on confrontation she disclosed her chronic ketamine abuse. Additionally, 6 months prior to this ED presentation, she was evaluated for similar symptoms, disclosed her ketamine use, and a urine sample was sent for gas chromatography/mass spectrometry that revealed a ketamine concentration of 100 ng/mL and norketamine concentration of 2200 ng/mL. She was admitted for pain management and social service coordination and discharged to substance abuse treatment after 7 days, though her pain and hematuria had not completely resolved. No further imaging was performed, but outpatient cystoscopy 3 months later revealed inflammatory changes of the bladder mucosa without lesions suspicious for malignancy or abnormalities in the ureters. The associations between heavy ketamine use and inflammation of both the urinary and gall bladders have been described in Asia and Europe where ketamine use is significantly higher than in North America.1 Epidemiological data suggest high ketamine doses and its more frequent use correlate with lower abdominal pain, polyuria, and dysuria.2 Ketamine administered chronically to mice resulted in bladder-wall thickening and mononuclear cell infiltration.3 Bladder volumes were smaller and pressure was higher in ketamine-treated mice. Additionally, findings of increased immunoreactivity to the P2X1 ATP receptor, (a ligand-gated ion channel) but not muscarinic receptors in the detrusor muscle are consistent with the human experience of treatment failures of cholinergic therapies. Further, the urothelium of mice exposed to chronic ketamine revealed increased numbers of apoptotic cells determined by TUNEL assay, increased concentrations of pro-apoptotic proteins and markers of oxidative stress, and decreased expression of urothelial tight junction proteins.4 Still, it remains unclear precisely how ketamine is associated with these findings and why reports of acute tubular necrosis or other renal toxicity are not associated. Ketamine and its metabolites can be found in the urine for about 1 week after exposure and in chronic users, prolonged
exposure to the bladder mucosa would be expected. Excretion is primarily renal but the small proportion eliminated in the bile may be the cause of inflammation in the gall bladder and CBD.1 A case series in heavy ketamine users reported fusiform dilation of the CBD without obstruction.5 Notably, these findings were reversible after drug discontinuation though the inflammatory changes of the urinary bladder are potentially irreversible.6 Clinicians managing patients with chronic pelvic and abdominal pain should consider ketamine-associated conditions in their differential diagnosis and screen for ketamine use.
Conclusion Diagnosis: Cystitis and CBD dilation due to chronic ketamine abuse.
Declaration of interest The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Kalsi SS, Wood DM, Dargan PI. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerg Health Threats J 2011; 4:7107. 2. Winstock AR, Mitcheson L, Gillatt DA, Cottrell AM. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int 2012; 110:1762–1766. 3. Meng E, Chang HY, Chang SY, Sun GH, Yu DS, Cha TL. Involvement of purinergic neurotransmission in ketamine induced bladder dysfunction. J Urol 2011; 186:1134–41. 4. Juan Y, Li Y, Chuang S, Chang C, Shen J, Jang M, Wu W. Urothelial dysfunction and increased apoptotic pathway in ketamine-induced ulcerative cystitis. Poster presented at: International Continence Society Annual Meeting; 2013 August 26–30; Barcelona, Spain. 5. Wong SW, Lee KF, Wong J, Ng WW, Cheung YS, Lai PB. Dilated common bile ducts mimicking choledochal cysts in ketamine abusers. Hong Kong Med J. 2009; 15:53–56. 6. Jalil R, Gupta S. Illicit ketamine and its bladder consequences: is it irreversible? BMJ Case Rep 2012; 2012.
Clinical Toxicology vol. 52 no. 3 2014
IMAGES
Chronic hematuria and abdominal pain N. J. CONNORS,1 A. GRINO,2 M. G. TUNIK,2 and R. S. HOFFMAN1 1Division
of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, New York, NY, USA of Emergency Medicine, New York University School of Medicine, New York, NY, USA
Clinical Toxicology Downloaded from informahealthcare.com by University of Laval on 07/10/14 For personal use only.
2Department
An 18-year-old Asian woman with a history of substance abuse presented to the Emergency Department with right-sided abdominal pain and hematuria of several months duration. Physical examination revealed right upper quadrant and suprapubic tenderness. Liver function tests were normal. Urinalysis showed: large blood, 30–50 red blood cells/high-powered field, and no bacteria. She underwent a CT of the abdomen and pelvis following oral and intravenous contrast. Keywords
Common bile duct dilation; Cystitis; Substance abuse
Presentation An 18-year-old Asian woman, 46.3 kg, presented to the Emergency Department (ED) with right-sided abdominal pain and hematuria of several months duration. Prior evaluation of her abdominal pain included an abdominal ultrasound that showed a dilated common bile duct (CBD), magnetic resonance cholangiopancreatography that revealed CBD dilation without evidence of choledocholithiasis, heptaobiliary iminodiacetic acid cholescintigraphy that noted delayed filling of the gall bladder, and an esophagogastroduodenoscopy that showed gastritis. Six days prior to this presentation she was seen in another ED, diagnosed with a urinary tract infection, and prescribed cephalexin, ketorolac, and hydrocodone/ acetaminophen, which she was taking. Her vital signs were as follows: BP, 119/86 mmHg; HR, 78/min; RR, 20/min; temperature, 98.8°F; and oxygen saturation, 100% on room air. Her physical examination was significant for white powder in her hair and tenderness in the right upper quadrant and suprapubic region without rebound or guarding. Liver function tests were normal. Urinalysis showed: large blood; small leukocyte esterase; white blood cells, 10–15/high powered field (HPF); red blood cells, 30–50/HPF; and no bacteria. Urine drug screen for phencyclidine was negative, but was positive for opiates. She underwent a CT of the abdomen and pelvis following oral and intravenous contrast (Fig. 1).
Diagnosis The CT showed marked distension of the gall bladder, a CBD diameter of 8 mm, and signs of inflammation of the Received 12 December 2013; accepted 4 February 2014.
Fig. 1. Coronal image from a CT of the abdomen and pelvis following oral and intravenous contrast showing signs of urinary bladder mucosal inflammation and CBD dilation to 8 mm. No obstructive stones or masses were noted. The kidney and ureters were unremarkable.
Address correspondence to Nicholas J. Connors, Division of Medical Toxicology, Department of Emergency Medicine, New York University School of Medicine, 455 First Ave, Room 123, New York, NY 10016, USA. E-mail: [email protected]
mucosal surface of the bladder. The kidneys and ureters were normal and no choledocholithiasis was seen on this or subsequent ultrasound imaging. Pathologies in the biliary and 231
Clinical Toxicology Downloaded from informahealthcare.com by University of Laval on 07/10/14 For personal use only.
232
N. J. Connors et al.
urinary tracts are suggestive findings in a substance abuser. During her ED stay a plastic bag of white powder fell from the patient’s purse and on confrontation she disclosed her chronic ketamine abuse. Additionally, 6 months prior to this ED presentation, she was evaluated for similar symptoms, disclosed her ketamine use, and a urine sample was sent for gas chromatography/mass spectrometry that revealed a ketamine concentration of 100 ng/mL and norketamine concentration of 2200 ng/mL. She was admitted for pain management and social service coordination and discharged to substance abuse treatment after 7 days, though her pain and hematuria had not completely resolved. No further imaging was performed, but outpatient cystoscopy 3 months later revealed inflammatory changes of the bladder mucosa without lesions suspicious for malignancy or abnormalities in the ureters. The associations between heavy ketamine use and inflammation of both the urinary and gall bladders have been described in Asia and Europe where ketamine use is significantly higher than in North America.1 Epidemiological data suggest high ketamine doses and its more frequent use correlate with lower abdominal pain, polyuria, and dysuria.2 Ketamine administered chronically to mice resulted in bladder-wall thickening and mononuclear cell infiltration.3 Bladder volumes were smaller and pressure was higher in ketamine-treated mice. Additionally, findings of increased immunoreactivity to the P2X1 ATP receptor, (a ligand-gated ion channel) but not muscarinic receptors in the detrusor muscle are consistent with the human experience of treatment failures of cholinergic therapies. Further, the urothelium of mice exposed to chronic ketamine revealed increased numbers of apoptotic cells determined by TUNEL assay, increased concentrations of pro-apoptotic proteins and markers of oxidative stress, and decreased expression of urothelial tight junction proteins.4 Still, it remains unclear precisely how ketamine is associated with these findings and why reports of acute tubular necrosis or other renal toxicity are not associated. Ketamine and its metabolites can be found in the urine for about 1 week after exposure and in chronic users, prolonged
exposure to the bladder mucosa would be expected. Excretion is primarily renal but the small proportion eliminated in the bile may be the cause of inflammation in the gall bladder and CBD.1 A case series in heavy ketamine users reported fusiform dilation of the CBD without obstruction.5 Notably, these findings were reversible after drug discontinuation though the inflammatory changes of the urinary bladder are potentially irreversible.6 Clinicians managing patients with chronic pelvic and abdominal pain should consider ketamine-associated conditions in their differential diagnosis and screen for ketamine use.
Conclusion Diagnosis: Cystitis and CBD dilation due to chronic ketamine abuse.
Declaration of interest The authors report no declarations of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Kalsi SS, Wood DM, Dargan PI. The epidemiology and patterns of acute and chronic toxicity associated with recreational ketamine use. Emerg Health Threats J 2011; 4:7107. 2. Winstock AR, Mitcheson L, Gillatt DA, Cottrell AM. The prevalence and natural history of urinary symptoms among recreational ketamine users. BJU Int 2012; 110:1762–1766. 3. Meng E, Chang HY, Chang SY, Sun GH, Yu DS, Cha TL. Involvement of purinergic neurotransmission in ketamine induced bladder dysfunction. J Urol 2011; 186:1134–41. 4. Juan Y, Li Y, Chuang S, Chang C, Shen J, Jang M, Wu W. Urothelial dysfunction and increased apoptotic pathway in ketamine-induced ulcerative cystitis. Poster presented at: International Continence Society Annual Meeting; 2013 August 26–30; Barcelona, Spain. 5. Wong SW, Lee KF, Wong J, Ng WW, Cheung YS, Lai PB. Dilated common bile ducts mimicking choledochal cysts in ketamine abusers. Hong Kong Med J. 2009; 15:53–56. 6. Jalil R, Gupta S. Illicit ketamine and its bladder consequences: is it irreversible? BMJ Case Rep 2012; 2012.
Clinical Toxicology vol. 52 no. 3 2014
