CASE-LETTER
Pipe Dreams: Concealed Methamphetamine Causing Severe Toxicity
M
ethamphetamine is a highly addictive and toxic drug of abuse. Hospital visits related to methamphetamine abuse have increased dramatically since 2007, with nearly 103,000 visits recorded in 2011. Methamphetamine is absorbed rapidly after delivery. The various routes of administration and their times of onset being oral (20–30 minutes), nasal (3–5 minutes), intravenous (15–30 seconds), inhaled (7–10 seconds), rectal (3– 5 minutes) and vaginal routes (3–5 minutes).1,2 We report a case of toxicity from rectal absorption of methamphetamine secondary to concealed drug paraphernalia. A 28-year-old man with schizoaffective disorder and polysubstance abuse was brought to the emergency department after a witnessed seizure. Vital signs revealed a blood pressure of 60/40 mm Hg, temperature of 104°F (40°C), pulse of 144 beats per minute and altered mental status. Fluid resuscitation was initiated in the emergency department, the patient was given 3 L of normal saline, and endotracheal intubation was performed. Physical examination was unremarkable except for the following: anisocoria (left pupil 3 mm and right pupil 8 mm), coarse vesicular bilateral breath sounds and 3 to 4 beats of inducible bilateral ankle clonus. There were no obvious signs of “skin popping” or track marks. Laboratory examination revealed a white cell count of 13,700 per microliter (13.70 3 109 per liter), hemoglobin 16.1 g/dL, sodium 141 mEq/L, potassium 5.5 mEq/L, chloride 103 mEq/L, carbon dioxide 11 mEq/L, BUN 14 mg/dL (832 mmol/L) (urea 5 mmol/L), creatinine 2.3 mg/dL (203.32 mmol/L), AST 42 IU/L, ALT 28 IU/L, troponin-I 0.26 ng/mL, lactic acid 39.64 mg/dL (4.4 mmol/L) and creatine kinase 355 IU/L. Urine toxicology screen was positive for methamphetamine; extended assays were negative for methcathinone and cathinone. A computed tomography scan of the head and chest radiograph were unremarkable. Bedside echocardiogram revealed severely reduced ejection fraction at 15% to 20% with global hypokinesis. The patient was admitted to the intensive care unit with multiorgan failure. Over the next 48 hours, the lactic acid level normalized and intravenous saline was continued as treatment of rhabdomyolysis. He developed markedly elevated transaminases and worsening renal function. A computed tomography scan of the abdomen and pelvis was performed to evaluate for evidence of body stuffing, and the radiologist noted the presence of a rectal tube (Figure 1). This prompted rectal examination, and methamphetamine paraphernalia including a pipe, remnants and intact packets of a powdery substance, consistent with methamphetamine, were removed. No other evidence of “body stuffing” was found. Treatment included volume resuscitation, vasopressors, empiric N-acetyl cysteine for liver injury, hemodialysis and other supportive therapy. There was ongoing renal dysfunction, evidenced by a rising creatinine, anuria and hyperkalemia requiring hemodialysis. His mental status improved allowing extubation. His anisocoria self-resolved by day 2 of admission, the cause for the anisocria and its significance remains obscure. The significant laboratory findings are shown in Table 1. The patient was hospitalized for 10 days and had a full recovery
548
FIGURE 1. Computed tomography of the abdomen and pelvis (coronal view) revealing the pipe (circle) in the rectum.
including normalization of renal and cardiac function with a repeat ejection fraction of 60% to 65%. Although the patient did not reveal why the drug paraphernalia were placed rectally, we believe it was to avoid detection by law enforcement. Methamphetamine abuse is a rapidly growing problem in the United States.1 The patient was critically ill with multiorgan failure from occult rectal absorption of methamphetamine and manifested hyperpyrexia, seizures, cardiomyopathy, hepatic injury and kidney injury with profound rhabdomyolysis. The clinical detection of the drug in the rectum was delayed. Methamphetamine absorption across the rectal mucosa through the anorectal-venous circulation can lead to toxicity in a variety of organs, many of which were seen in the patient. Unusual methods of methamphetamine administration have been described and include vaginal stuffing, self-administered methamphetamine enema and a methamphetamine-laced rectal tampon.3–5 The patient also developed significant hepatic injury. Hepatitis was reported as the 2nd most common clinical presentation in an early analysis of acute methamphetamine toxicity. Volkow et al6 demonstrated with PET scan and [C11] D-methamphetamine that the accumulation of this drug and its metabolites in hepatic tissue was very high in healthy nonabusing adult men.7 It is notable that methamphetamine is excreted through the biliary tree. The exact cellular and molecular mechanisms involved in methamphetamine-induced hepatotoxicity are not well understood. In 1 investigation in freshly isolated rat hepatocytes, methamphetamine cytotoxicity resulted in oxidative stress—reactive oxygen species formation, lipid peroxidation and glutathione depletion. This in turn produced a decrease in mitochondrial membrane potential and release of cytochrome C, finally resulting in cell lysis.7 Thus, free radical scavengers like N-acetyl cysteine may be theoretically protective but clinical research is required. Hyperthermia caused by methamphetamine can worsen liver injury.8
The American Journal of the Medical Sciences
Volume 349, Number 6, June 2015
Case-Letter
TABLE 1. Significant laboratory values Laboratory Value Reference Range
Admission
Peak (Hospital Day)
Discharge
Creatine kinase, IU/L Troponin-I, ng/mL Creatinine, mg/dL [mmol/L] AST, IU/L ALT, IU/L
355 0.26 2.3 [203.32] 72 28
432,160 (day 2) 32 (day 1) 10.3 (day 6) 2,766 (day 3) 3,065 (day 3)
563 14.15a 6.7 [510.88] 75 209
a
40–150 0–0.4 0.1–0.4 (8–31) 10–30 10–40
Troponin not followed until discharge, last checked downtrending value.
This case highlights many important clinical features of severe methamphetamine toxicity in the intensive care unit. It reminds clinicians that the route of methamphetamine administration may be unusual and cases of body stuffing should be considered in cases of toxicity.
Ramasubramanian Baalachandran, Cameron Hypes, *Bhupinder Natt, Linda Snyder,
MD MD MD MD
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona Tucson, AZ *E-mail: [email protected] The authors have no financial or other conflicts of interest to disclose. REFERENCES 1. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. The DAWN Report:
Copyright Ó 2015 by the Southern Society for Clinical Investigation.
Emergency Department Visits Involving Methamphetamine: 2007 to 2011. Rockville, MD. 2014. 2. Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: an update. Arch Toxicol 2012;86:1167–1231. 3. Kashani J, Ruha AM. Methamphetamine toxicity secondary to intravaginal body stuffing. J Toxicol Clin Toxicol 2004;42:987–989. 4. Cantrell FL, Breckenridge HM, Jost P. Transrectal methamphetamine use: a novel route of exposure. Ann Intern Med 2006;145:78–79. 5. Gupta M, Bailey S, Lovato LM. Bottoms up: methamphetamine toxicity from an unusual route. West J Emerg Med 2009;10:58–60. 6. Volkow ND, Fowler JS, Wang GJ, et al. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications. PLoS One 2010;5:e15269. 7. Eskandari MR, Rahmati M, Khajeamiri AR, et al. A new approach on methamphetamine-induced hepatotoxicity: involvement of mitochondrial dysfunction. Xenobiotica 2014;44:70–76. 8. Halpin LE, Gunning WT, Yamamoto BK. Methamphetamine causes acute hyperthermia-dependent liver damage. Pharma Res Perspect 2013; 1:e00008.
549
Pipe Dreams: Concealed Methamphetamine Causing Severe Toxicity
M
ethamphetamine is a highly addictive and toxic drug of abuse. Hospital visits related to methamphetamine abuse have increased dramatically since 2007, with nearly 103,000 visits recorded in 2011. Methamphetamine is absorbed rapidly after delivery. The various routes of administration and their times of onset being oral (20–30 minutes), nasal (3–5 minutes), intravenous (15–30 seconds), inhaled (7–10 seconds), rectal (3– 5 minutes) and vaginal routes (3–5 minutes).1,2 We report a case of toxicity from rectal absorption of methamphetamine secondary to concealed drug paraphernalia. A 28-year-old man with schizoaffective disorder and polysubstance abuse was brought to the emergency department after a witnessed seizure. Vital signs revealed a blood pressure of 60/40 mm Hg, temperature of 104°F (40°C), pulse of 144 beats per minute and altered mental status. Fluid resuscitation was initiated in the emergency department, the patient was given 3 L of normal saline, and endotracheal intubation was performed. Physical examination was unremarkable except for the following: anisocoria (left pupil 3 mm and right pupil 8 mm), coarse vesicular bilateral breath sounds and 3 to 4 beats of inducible bilateral ankle clonus. There were no obvious signs of “skin popping” or track marks. Laboratory examination revealed a white cell count of 13,700 per microliter (13.70 3 109 per liter), hemoglobin 16.1 g/dL, sodium 141 mEq/L, potassium 5.5 mEq/L, chloride 103 mEq/L, carbon dioxide 11 mEq/L, BUN 14 mg/dL (832 mmol/L) (urea 5 mmol/L), creatinine 2.3 mg/dL (203.32 mmol/L), AST 42 IU/L, ALT 28 IU/L, troponin-I 0.26 ng/mL, lactic acid 39.64 mg/dL (4.4 mmol/L) and creatine kinase 355 IU/L. Urine toxicology screen was positive for methamphetamine; extended assays were negative for methcathinone and cathinone. A computed tomography scan of the head and chest radiograph were unremarkable. Bedside echocardiogram revealed severely reduced ejection fraction at 15% to 20% with global hypokinesis. The patient was admitted to the intensive care unit with multiorgan failure. Over the next 48 hours, the lactic acid level normalized and intravenous saline was continued as treatment of rhabdomyolysis. He developed markedly elevated transaminases and worsening renal function. A computed tomography scan of the abdomen and pelvis was performed to evaluate for evidence of body stuffing, and the radiologist noted the presence of a rectal tube (Figure 1). This prompted rectal examination, and methamphetamine paraphernalia including a pipe, remnants and intact packets of a powdery substance, consistent with methamphetamine, were removed. No other evidence of “body stuffing” was found. Treatment included volume resuscitation, vasopressors, empiric N-acetyl cysteine for liver injury, hemodialysis and other supportive therapy. There was ongoing renal dysfunction, evidenced by a rising creatinine, anuria and hyperkalemia requiring hemodialysis. His mental status improved allowing extubation. His anisocoria self-resolved by day 2 of admission, the cause for the anisocria and its significance remains obscure. The significant laboratory findings are shown in Table 1. The patient was hospitalized for 10 days and had a full recovery
548
FIGURE 1. Computed tomography of the abdomen and pelvis (coronal view) revealing the pipe (circle) in the rectum.
including normalization of renal and cardiac function with a repeat ejection fraction of 60% to 65%. Although the patient did not reveal why the drug paraphernalia were placed rectally, we believe it was to avoid detection by law enforcement. Methamphetamine abuse is a rapidly growing problem in the United States.1 The patient was critically ill with multiorgan failure from occult rectal absorption of methamphetamine and manifested hyperpyrexia, seizures, cardiomyopathy, hepatic injury and kidney injury with profound rhabdomyolysis. The clinical detection of the drug in the rectum was delayed. Methamphetamine absorption across the rectal mucosa through the anorectal-venous circulation can lead to toxicity in a variety of organs, many of which were seen in the patient. Unusual methods of methamphetamine administration have been described and include vaginal stuffing, self-administered methamphetamine enema and a methamphetamine-laced rectal tampon.3–5 The patient also developed significant hepatic injury. Hepatitis was reported as the 2nd most common clinical presentation in an early analysis of acute methamphetamine toxicity. Volkow et al6 demonstrated with PET scan and [C11] D-methamphetamine that the accumulation of this drug and its metabolites in hepatic tissue was very high in healthy nonabusing adult men.7 It is notable that methamphetamine is excreted through the biliary tree. The exact cellular and molecular mechanisms involved in methamphetamine-induced hepatotoxicity are not well understood. In 1 investigation in freshly isolated rat hepatocytes, methamphetamine cytotoxicity resulted in oxidative stress—reactive oxygen species formation, lipid peroxidation and glutathione depletion. This in turn produced a decrease in mitochondrial membrane potential and release of cytochrome C, finally resulting in cell lysis.7 Thus, free radical scavengers like N-acetyl cysteine may be theoretically protective but clinical research is required. Hyperthermia caused by methamphetamine can worsen liver injury.8
The American Journal of the Medical Sciences
Volume 349, Number 6, June 2015
Case-Letter
TABLE 1. Significant laboratory values Laboratory Value Reference Range
Admission
Peak (Hospital Day)
Discharge
Creatine kinase, IU/L Troponin-I, ng/mL Creatinine, mg/dL [mmol/L] AST, IU/L ALT, IU/L
355 0.26 2.3 [203.32] 72 28
432,160 (day 2) 32 (day 1) 10.3 (day 6) 2,766 (day 3) 3,065 (day 3)
563 14.15a 6.7 [510.88] 75 209
a
40–150 0–0.4 0.1–0.4 (8–31) 10–30 10–40
Troponin not followed until discharge, last checked downtrending value.
This case highlights many important clinical features of severe methamphetamine toxicity in the intensive care unit. It reminds clinicians that the route of methamphetamine administration may be unusual and cases of body stuffing should be considered in cases of toxicity.
Ramasubramanian Baalachandran, Cameron Hypes, *Bhupinder Natt, Linda Snyder,
MD MD MD MD
Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona Tucson, AZ *E-mail: [email protected] The authors have no financial or other conflicts of interest to disclose. REFERENCES 1. Substance Abuse and Mental Health Services Administration, Center for Behavioral Health Statistics and Quality. The DAWN Report:
Copyright Ó 2015 by the Southern Society for Clinical Investigation.
Emergency Department Visits Involving Methamphetamine: 2007 to 2011. Rockville, MD. 2014. 2. Carvalho M, Carmo H, Costa VM, et al. Toxicity of amphetamines: an update. Arch Toxicol 2012;86:1167–1231. 3. Kashani J, Ruha AM. Methamphetamine toxicity secondary to intravaginal body stuffing. J Toxicol Clin Toxicol 2004;42:987–989. 4. Cantrell FL, Breckenridge HM, Jost P. Transrectal methamphetamine use: a novel route of exposure. Ann Intern Med 2006;145:78–79. 5. Gupta M, Bailey S, Lovato LM. Bottoms up: methamphetamine toxicity from an unusual route. West J Emerg Med 2009;10:58–60. 6. Volkow ND, Fowler JS, Wang GJ, et al. Distribution and pharmacokinetics of methamphetamine in the human body: clinical implications. PLoS One 2010;5:e15269. 7. Eskandari MR, Rahmati M, Khajeamiri AR, et al. A new approach on methamphetamine-induced hepatotoxicity: involvement of mitochondrial dysfunction. Xenobiotica 2014;44:70–76. 8. Halpin LE, Gunning WT, Yamamoto BK. Methamphetamine causes acute hyperthermia-dependent liver damage. Pharma Res Perspect 2013; 1:e00008.
549
