case report Wien Klin Wochenschr (2014) 126:291–293 DOI 10.1007/s00508-014-0523-7
Acute kidney injury with medazepam-hyoscine buthylbromide Zeynel Abidin Sayiner · Zeynel Abidin Ozturk
Received: 28 July 2013 / Accepted: 5 February 2014 / Published online: 25 March 2014 © Springer-Verlag Wien 2014
Summary An 84-year-old female patient was admitted to our internal medicine outpatient clinic complaining of stomach ache, nausea, and vomiting. She had hepatitis C infection for 10 years that was managed with antiviral treatment. On the second day of admission, she developed anxiety and complained about dysuria. Medazepam and hyoscine butylbromide combined tablet was administered. The day after medazepam and hyoscine butylbromide administration, patient’s creatinine level increased to 2.3 mg/dL (0.57–1.11 mg/dL). Medazepam and hyoscine butylbromide administration was stopped on the fourth day. After 10 days of follow-up, her creatinine levels were normalized. In this article, we present an elderly patient with acute kidney injury induced by medazepam and hyoscine butylbromide that was managed with best supportive care. Keywords Medazepam and hyoscine butylbromide · Acute renal failure · Elderly patients
Akutes Nierenversagen durch MedazepamHyoscin Butylbromid Zusammenfassung Eine 84-jährige Patientin präsentierte sich in unserer Ambulanz für Innere Medizin mit Magenschmerzen, Übelkeit und Erbrechen. Sie hatte seit 10 Jahren eine Infektion mit Hepatitis C, die unter anti-
Z. A. Sayiner, MD () Department of Internal Medicine, Gaziantep University Faculty of Medicine, 27100 Sahinbey, Gaziantep, Turkey e-mail: [email protected] Z. A. Ozturk Division of Geriatric Medicine, Department of Internal Medicine, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
13
viraler Therapie stand. Am 2. Tag nach der stationären Aufnahme klagte sie über Beklemmungen und Dysurie. Sie erhielt Medazepam und Hyoscin Butylbromid in einer Kombinationstablette. Am Tag nach der Verabreichung stieg das Kreatinin auf 2,3 mg/dL (0,57–1,11 mg/ dL). Die kombinierte Gabe von Medazepam und Hyoscin Butylbromid wurde am Tag 4 beendet. Bei der Kontrolle 10 Tage später waren die Kreatinin Spiegel wieder im Normbereich. Im vorliegenden Artikel berichten wir über eine ältere Patientin mit einem durch Medazepam kombiniert mit Hyoscin Butylbromid induziertem akuten Nierenversagen, das sich nach Absetzen ohne weitere spezifische Maßnahmen wieder besserte. Schlüsselwörter Medazepam und Hyoscin Butylbromid · Akutes Nierenversagen · Ältere Patienten
Introduction Benzodiazepines are a class of drugs with anxiolytic, sedative, muscle-relaxant, and hypnotic effects commonly used in the treatment of insomnia and anxiety disorders [1]. The most prominent of these effects are sedation, decreased anxiety, muscle relaxation, and anticonvulsant activity. Only two effects of these drugs result from peripheral actions, coronary vasodilation, and neuromuscular blockade, seen only with very high doses [2]. All anxiolytic benzodiazepines have almost the same side effect profile. Hyoscine butylbromide is an antispasmodic drug indicated for the treatment of abdominal pain associated with cramps induced by gastrointestinal spasms [3]. We herein describe an elderly patient having used a combination of medazepam and hyoscine-Nbutylbromide for anxiety and who developed acute renal failure.
Acute kidney injury with medazepam–hyoscine buthylbromide
291
case report Case An 84-year-old female patient was admitted to our internal medicine outpatient clinic complaining of fatigue, stomach ache, nausea, and vomiting. She had a 10-year history of hepatitis C infection. Her last hepatitis C virus RNA evaluation was negative. Onset of symptoms was 2 days prior. On physical examination, it was found that she had tenderness in the lower mid-zone of the abdomen. No peripheral cirrhotic signs were found during the physical examination. She had no fever. Laboratory analyses of the hematological parameters revealed the following: hemoglobin: 10.8 g/dL (13–16 g/dL), white blood cells: 5 × 103 lL (4 × 103−10 × 103/lL), thrombocytes: 453 × 103/mm3 (150 × 103/mm3−400 × 103/mm3), erythrocyte sedimentation rate: 24 mm/h (1–15 mm/h), C reactive protein (CRP): 23.7 mg/L (0–9 mg/L), and ferritin: 9,146 ng/mL (14–150 ng/mL). Biochemical analysis of blood revealed the following: urea: 20 mg/dL (10–50 mg/ dL), creatinine: 0.7 mg/dL (0.57–1.11 mg/dL), glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI): 80 mL/min/1.73 m2 [4], total bilirubin: 0.8 mg/dL (0.2–1.2 mg/dL), indirect bilirubin: 0.5 mg/dL (0.2–0.7 mg/dL), glucose: 100 mg/ dL (70–109 mg/dL), aspartate aminotransferase (AST): 25 U/L (5–34 U/L), alanine aminotransferase (ALT): 25 U/L (5–34 U/L), gama glutamine tranferase (GGT): 9 U/L (10–71 U/L), Alkaline phosphatase (ALP): 68 U/L (40–129 U/L), and lactic dehydrogenase: 219 U/L (125– 243 U/L). Analysis of urine parameters revealed the following: density: 1,018 mg/dl (1,005–1,020 mg/dl), protein (−), urobilinogen (−), bilirubin (−), ketone (−), and leukocyte esterase (++), but no leukocyturia. The levels of blood electrolytes and amylase were in normal ranges. In peripheral blood smears, we observed normocytic, normochromic erythrocytes with normal numbers of thrombocytes and no atypical blood cells. Abdominal ultrasonography was performed, and there was no pathologic finding. A posterior–anterior X-ray of the chest was normal. The patient was admitted to the Internal Medicine Department for further evaluations. On the second day of admission, the patient developed anxiety and complained about dysuria. Medazepam and hyoscine butylbromide combined tablet was administered to the patient once a day for her anxiety. The day after medazepam and hyoscine butylbromide administration, the patient’s creatinine level increased to 2.3 mg/dL (0.57– 1.11 mg/dL), blood urea value was 90 mg/dL (10–50 mg/ dL), and uric acid level was 7 mg/dL (2–6 mg/dL). No additional drugs were administered except medazepam, hyoscine butylbromide, and omeprazole. Abdominal and renal ultrasonography results were normal. Upper endoscopy revealed esophagitis. Urine culture showed extended-spectrum beta lactamase-positive Escherichia coli growth. Meropenem was administered to the patient with corrected renal dose. In the follow-up, the patient’s creatinine elevation persisted for 10 days. Medazepam and hyoscine butylbromide were stopped on the fourth day of treatment. The patient was treated with merope-
292 Acute kidney injury with medazepam–hyoscine buthylbromide
nem, omeprazole, and hydration. After 2 weeks, her kidney function tests were normalized, and in control urine culture, there was no infection sign.
Discussion We herein describe an elderly patient with acute renal failure after using medazepam and hyoscine butylbromide for her anxiety. Pharmacologic effects include reduction of anxiety, suppression of seizure activity, and Central nervous system (CNS) depression. It may cause respiratory arrest and precipitate or worsen hepatic encephalopathy cardiotoxicity. Patients receiving highdose Lorazepam are at risk for toxicity from propylene glycol [5]. Patients receiving greater than the recommended daily dose of this drug should be monitored for toxicity with daily osmolar gap measurements. However, this recommendation is only for propylene glycol, including benzodiazepines [6], as known benzodiazepines are metabolized extensively by hepatic Cytochrome c peroxidase (CYPs) [2]. Acute kidney injury is a common clinical problem [7]. Our patient’s radiologic examination did not reveal any signs of postrenal causes. Also, our patient had no volume depletion, hypotension, and sepsis signs. A number of drugs can cause Acute tubuler necrosis (ATN) such as aminoglycosides, cisplatin, acetaminophen, ibuprofen, Nonsteroidal anti inflammatory drugs (NSAIDs), Angiotension converting enzyme (ACE) inhibitors, and Angiotension reseptor blockers (ARBs) [8, 9]. So far, there have been no certain data about whether benzodiazepines cause renal toxicity. Even there have been some data showing that benzodiazepines can be used safely for regular sleep pattern in patients with chronic kidney failure [10, 11]. However, some available data show that benzodiazepines may cause renal tubular acidosis [4, 12]. Aging results in changes in organ function, especially of the organs involved in drug disposition. Initial doses should be less than the usual adult dosage and should be increased slowly. The number of medications, and doses per day, should be kept as low as possible. Elderly patients are at greater risk for adverse drug events due to metabolic changes and decreased drug clearance [13]. To our knowledge, this is the first reported case of acute kidney injury associated with medazepam. We recommend elderly patients taking medazepam to be monitored with regular complete blood test check for clinically significant acute kidney injury. More importantly in elderly patients, initial doses should be less than the usual adult doses, and these patients should reconsider before starting a new drug. Conflict of interest To the best of our knowledge, none of the authors has any direct or indirect conflicts of interest, financial or otherwise, relating to the subject of our report.
13
case report References 1. Buffett-Jerrott SE, Stewart SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des. 2002;8(1):45–58. 2. Charney DS, Mihic SJ, Harris RA. Chap. 17: Hypnotics and sedatives. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed, Section II, Neuropharmacology. New York: McGraw-Hill; 2011. 3. Tytgat GN. Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs. 2007 June;67(9):1343–57. 4. Zar T, et al. Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam. Nat Clin Pract Nephrol. 2007;3:517–20. 5. Chap. 31: Benzodiazepines. In: Olson KR, editor. Poisoning & drug overdose. 6th ed. New York: McGraw-Hill; 2012. 6. Margolias G, Harris RS. Chap. 135: Analgesia paralytics and sedation. In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS, editors. Principles and practice of hospital medicine. McGraw-Hill; 2012. pp. 1070–81. 7. Liangos O, Wald R, O’Bell JW, Price L, Pereira BJ, Jaber BL. Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol. 2006;1(1):43.
13
8. Rosner MH, Okusa MD. Drug-associated acute renal failure in the intensive care unit. In: De Broe ME, Porter GA, Bennett WM, Deray G, editors. Clinical nephrotoxins: renal injury from drugs and chemicals. 3rd ed. Boston: Kluwer Academic Press; 2008. 9. Chap. 57: Assessment and evaluation of the renal patient, acute kidney injury specific syndromes. In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS, editors. Principles and practice of hospital medicine. McGraw-Hill; 2012. pp. 378–90. 10. Wyne A, Rai R, Cuerden M, Clark WF, Suri RS. Opioid and benzodiazepine use in end-stage renal disease: a systematic review. Clin J Am Soc Nephrol. 2011 Feb;6(2):326–33. 11. Unruh ML, Buysse DJ, Dew MA, Evans IV, Wu AW, Fink NE. Sleep quality and its correlates in the first year of dialysis. Clin J Am Soc Nephrol. 2006;1:802–10. 12. Hayman M, Seidl EC, Ali M, Malik K. Acute tubular necrosis associated with propylene glycol from concomitant administration of intravenous lorazepam and trimethoprim-sulfamethoxazole. Pharmacotherapy. 2003 Sept;23(9):1190–4. 13. Steinman MA, Hanlon JT. Managing medications in clinically complex elders: there’s got to be a happy medium. JAMA. 2010;304(14):1592.
Acute kidney injury with medazepam–hyoscine buthylbromide
293
Acute kidney injury with medazepam-hyoscine buthylbromide Zeynel Abidin Sayiner · Zeynel Abidin Ozturk
Received: 28 July 2013 / Accepted: 5 February 2014 / Published online: 25 March 2014 © Springer-Verlag Wien 2014
Summary An 84-year-old female patient was admitted to our internal medicine outpatient clinic complaining of stomach ache, nausea, and vomiting. She had hepatitis C infection for 10 years that was managed with antiviral treatment. On the second day of admission, she developed anxiety and complained about dysuria. Medazepam and hyoscine butylbromide combined tablet was administered. The day after medazepam and hyoscine butylbromide administration, patient’s creatinine level increased to 2.3 mg/dL (0.57–1.11 mg/dL). Medazepam and hyoscine butylbromide administration was stopped on the fourth day. After 10 days of follow-up, her creatinine levels were normalized. In this article, we present an elderly patient with acute kidney injury induced by medazepam and hyoscine butylbromide that was managed with best supportive care. Keywords Medazepam and hyoscine butylbromide · Acute renal failure · Elderly patients
Akutes Nierenversagen durch MedazepamHyoscin Butylbromid Zusammenfassung Eine 84-jährige Patientin präsentierte sich in unserer Ambulanz für Innere Medizin mit Magenschmerzen, Übelkeit und Erbrechen. Sie hatte seit 10 Jahren eine Infektion mit Hepatitis C, die unter anti-
Z. A. Sayiner, MD () Department of Internal Medicine, Gaziantep University Faculty of Medicine, 27100 Sahinbey, Gaziantep, Turkey e-mail: [email protected] Z. A. Ozturk Division of Geriatric Medicine, Department of Internal Medicine, Gaziantep University Faculty of Medicine, Gaziantep, Turkey
13
viraler Therapie stand. Am 2. Tag nach der stationären Aufnahme klagte sie über Beklemmungen und Dysurie. Sie erhielt Medazepam und Hyoscin Butylbromid in einer Kombinationstablette. Am Tag nach der Verabreichung stieg das Kreatinin auf 2,3 mg/dL (0,57–1,11 mg/ dL). Die kombinierte Gabe von Medazepam und Hyoscin Butylbromid wurde am Tag 4 beendet. Bei der Kontrolle 10 Tage später waren die Kreatinin Spiegel wieder im Normbereich. Im vorliegenden Artikel berichten wir über eine ältere Patientin mit einem durch Medazepam kombiniert mit Hyoscin Butylbromid induziertem akuten Nierenversagen, das sich nach Absetzen ohne weitere spezifische Maßnahmen wieder besserte. Schlüsselwörter Medazepam und Hyoscin Butylbromid · Akutes Nierenversagen · Ältere Patienten
Introduction Benzodiazepines are a class of drugs with anxiolytic, sedative, muscle-relaxant, and hypnotic effects commonly used in the treatment of insomnia and anxiety disorders [1]. The most prominent of these effects are sedation, decreased anxiety, muscle relaxation, and anticonvulsant activity. Only two effects of these drugs result from peripheral actions, coronary vasodilation, and neuromuscular blockade, seen only with very high doses [2]. All anxiolytic benzodiazepines have almost the same side effect profile. Hyoscine butylbromide is an antispasmodic drug indicated for the treatment of abdominal pain associated with cramps induced by gastrointestinal spasms [3]. We herein describe an elderly patient having used a combination of medazepam and hyoscine-Nbutylbromide for anxiety and who developed acute renal failure.
Acute kidney injury with medazepam–hyoscine buthylbromide
291
case report Case An 84-year-old female patient was admitted to our internal medicine outpatient clinic complaining of fatigue, stomach ache, nausea, and vomiting. She had a 10-year history of hepatitis C infection. Her last hepatitis C virus RNA evaluation was negative. Onset of symptoms was 2 days prior. On physical examination, it was found that she had tenderness in the lower mid-zone of the abdomen. No peripheral cirrhotic signs were found during the physical examination. She had no fever. Laboratory analyses of the hematological parameters revealed the following: hemoglobin: 10.8 g/dL (13–16 g/dL), white blood cells: 5 × 103 lL (4 × 103−10 × 103/lL), thrombocytes: 453 × 103/mm3 (150 × 103/mm3−400 × 103/mm3), erythrocyte sedimentation rate: 24 mm/h (1–15 mm/h), C reactive protein (CRP): 23.7 mg/L (0–9 mg/L), and ferritin: 9,146 ng/mL (14–150 ng/mL). Biochemical analysis of blood revealed the following: urea: 20 mg/dL (10–50 mg/ dL), creatinine: 0.7 mg/dL (0.57–1.11 mg/dL), glomerular filtration rate Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI): 80 mL/min/1.73 m2 [4], total bilirubin: 0.8 mg/dL (0.2–1.2 mg/dL), indirect bilirubin: 0.5 mg/dL (0.2–0.7 mg/dL), glucose: 100 mg/ dL (70–109 mg/dL), aspartate aminotransferase (AST): 25 U/L (5–34 U/L), alanine aminotransferase (ALT): 25 U/L (5–34 U/L), gama glutamine tranferase (GGT): 9 U/L (10–71 U/L), Alkaline phosphatase (ALP): 68 U/L (40–129 U/L), and lactic dehydrogenase: 219 U/L (125– 243 U/L). Analysis of urine parameters revealed the following: density: 1,018 mg/dl (1,005–1,020 mg/dl), protein (−), urobilinogen (−), bilirubin (−), ketone (−), and leukocyte esterase (++), but no leukocyturia. The levels of blood electrolytes and amylase were in normal ranges. In peripheral blood smears, we observed normocytic, normochromic erythrocytes with normal numbers of thrombocytes and no atypical blood cells. Abdominal ultrasonography was performed, and there was no pathologic finding. A posterior–anterior X-ray of the chest was normal. The patient was admitted to the Internal Medicine Department for further evaluations. On the second day of admission, the patient developed anxiety and complained about dysuria. Medazepam and hyoscine butylbromide combined tablet was administered to the patient once a day for her anxiety. The day after medazepam and hyoscine butylbromide administration, the patient’s creatinine level increased to 2.3 mg/dL (0.57– 1.11 mg/dL), blood urea value was 90 mg/dL (10–50 mg/ dL), and uric acid level was 7 mg/dL (2–6 mg/dL). No additional drugs were administered except medazepam, hyoscine butylbromide, and omeprazole. Abdominal and renal ultrasonography results were normal. Upper endoscopy revealed esophagitis. Urine culture showed extended-spectrum beta lactamase-positive Escherichia coli growth. Meropenem was administered to the patient with corrected renal dose. In the follow-up, the patient’s creatinine elevation persisted for 10 days. Medazepam and hyoscine butylbromide were stopped on the fourth day of treatment. The patient was treated with merope-
292 Acute kidney injury with medazepam–hyoscine buthylbromide
nem, omeprazole, and hydration. After 2 weeks, her kidney function tests were normalized, and in control urine culture, there was no infection sign.
Discussion We herein describe an elderly patient with acute renal failure after using medazepam and hyoscine butylbromide for her anxiety. Pharmacologic effects include reduction of anxiety, suppression of seizure activity, and Central nervous system (CNS) depression. It may cause respiratory arrest and precipitate or worsen hepatic encephalopathy cardiotoxicity. Patients receiving highdose Lorazepam are at risk for toxicity from propylene glycol [5]. Patients receiving greater than the recommended daily dose of this drug should be monitored for toxicity with daily osmolar gap measurements. However, this recommendation is only for propylene glycol, including benzodiazepines [6], as known benzodiazepines are metabolized extensively by hepatic Cytochrome c peroxidase (CYPs) [2]. Acute kidney injury is a common clinical problem [7]. Our patient’s radiologic examination did not reveal any signs of postrenal causes. Also, our patient had no volume depletion, hypotension, and sepsis signs. A number of drugs can cause Acute tubuler necrosis (ATN) such as aminoglycosides, cisplatin, acetaminophen, ibuprofen, Nonsteroidal anti inflammatory drugs (NSAIDs), Angiotension converting enzyme (ACE) inhibitors, and Angiotension reseptor blockers (ARBs) [8, 9]. So far, there have been no certain data about whether benzodiazepines cause renal toxicity. Even there have been some data showing that benzodiazepines can be used safely for regular sleep pattern in patients with chronic kidney failure [10, 11]. However, some available data show that benzodiazepines may cause renal tubular acidosis [4, 12]. Aging results in changes in organ function, especially of the organs involved in drug disposition. Initial doses should be less than the usual adult dosage and should be increased slowly. The number of medications, and doses per day, should be kept as low as possible. Elderly patients are at greater risk for adverse drug events due to metabolic changes and decreased drug clearance [13]. To our knowledge, this is the first reported case of acute kidney injury associated with medazepam. We recommend elderly patients taking medazepam to be monitored with regular complete blood test check for clinically significant acute kidney injury. More importantly in elderly patients, initial doses should be less than the usual adult doses, and these patients should reconsider before starting a new drug. Conflict of interest To the best of our knowledge, none of the authors has any direct or indirect conflicts of interest, financial or otherwise, relating to the subject of our report.
13
case report References 1. Buffett-Jerrott SE, Stewart SH. Cognitive and sedative effects of benzodiazepine use. Curr Pharm Des. 2002;8(1):45–58. 2. Charney DS, Mihic SJ, Harris RA. Chap. 17: Hypnotics and sedatives. In: Brunton LL, Chabner BA, Knollmann BC, editors. Goodman & Gilman’s the pharmacological basis of therapeutics. 12th ed, Section II, Neuropharmacology. New York: McGraw-Hill; 2011. 3. Tytgat GN. Hyoscine butylbromide: a review of its use in the treatment of abdominal cramping and pain. Drugs. 2007 June;67(9):1343–57. 4. Zar T, et al. Acute kidney injury, hyperosmolality and metabolic acidosis associated with lorazepam. Nat Clin Pract Nephrol. 2007;3:517–20. 5. Chap. 31: Benzodiazepines. In: Olson KR, editor. Poisoning & drug overdose. 6th ed. New York: McGraw-Hill; 2012. 6. Margolias G, Harris RS. Chap. 135: Analgesia paralytics and sedation. In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS, editors. Principles and practice of hospital medicine. McGraw-Hill; 2012. pp. 1070–81. 7. Liangos O, Wald R, O’Bell JW, Price L, Pereira BJ, Jaber BL. Epidemiology and outcomes of acute renal failure in hospitalized patients: a national survey. Clin J Am Soc Nephrol. 2006;1(1):43.
13
8. Rosner MH, Okusa MD. Drug-associated acute renal failure in the intensive care unit. In: De Broe ME, Porter GA, Bennett WM, Deray G, editors. Clinical nephrotoxins: renal injury from drugs and chemicals. 3rd ed. Boston: Kluwer Academic Press; 2008. 9. Chap. 57: Assessment and evaluation of the renal patient, acute kidney injury specific syndromes. In: McKean SC, Ross JJ, Dressler DD, Brotman DJ, Ginsberg JS, editors. Principles and practice of hospital medicine. McGraw-Hill; 2012. pp. 378–90. 10. Wyne A, Rai R, Cuerden M, Clark WF, Suri RS. Opioid and benzodiazepine use in end-stage renal disease: a systematic review. Clin J Am Soc Nephrol. 2011 Feb;6(2):326–33. 11. Unruh ML, Buysse DJ, Dew MA, Evans IV, Wu AW, Fink NE. Sleep quality and its correlates in the first year of dialysis. Clin J Am Soc Nephrol. 2006;1:802–10. 12. Hayman M, Seidl EC, Ali M, Malik K. Acute tubular necrosis associated with propylene glycol from concomitant administration of intravenous lorazepam and trimethoprim-sulfamethoxazole. Pharmacotherapy. 2003 Sept;23(9):1190–4. 13. Steinman MA, Hanlon JT. Managing medications in clinically complex elders: there’s got to be a happy medium. JAMA. 2010;304(14):1592.
Acute kidney injury with medazepam–hyoscine buthylbromide
293
