It has been postulated that this effect may be partly due to the antibacterial properties of CBS against Campylobacter pylori, a bacterium found in the gastric mucosa and gastric metaplasia within the duodenum of most patients wi… 7. On the 3 rd day the CVVHDF treatment BUN and Cr values decreased to 14 mg/dl and 0.78 mg/dl, respectively. lesions. Chelation therapy promises to be an alternative treatment method. However, CBS has the advantage of slower ulcer relapse rates than those seen after initial healing with the H2-antagonists. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. In some cases, adults can take over-the-counter medicines such as loperamide (Imodium) and bismuth subsalicylate (Pepto-Bismol, Kaopectate) to treat diarrhea caused by food poisoning. Brain CT scan and MRI were both normal. The levels of bismuth in urine, blood and CSF samples confirm the intoxication by this agent [5, 13]. We had the opportunity to take care of 2 patients with myoclonic encephalopathy due to bismuth salts intoxication. Atomic Nanogenerators in Targeted Alpha Therapies: Curie's Legacy in Modern Cancer Management. Gastroenterology 99 (1990): 863-75. Toxicity Bismuth toxicity is associated primarily with exposure to bismuth salts, notably the ingestion of bismuth chelate. Although bismuth poisoning is still a rare phenomenon, the increasing use of bismuth-containing drugs warrants a systematic approach to the treatment of bismuth overdose. Summary: A number of seemingly neurotic symptoms, similar to those reported in bismuth intoxication, occurred in a patient taking a … BAL, DPA, DMPS, and DMSA have been used. It has been postulate … On the 3 rd day the CVVHDF treatment BUN and Cr values decreased to 14 mg/dl and 0.78 mg/dl, respectively. Bismuth subnitrate and carbonate are used in surgical dressings and bismuth chelate (tripotassium dicitratobismuthate) is used in the treatment of gastric and duodenal ulcers. Key Words: Acute Kidney Injury; Children; Colloidal Bismuth Subcitrate; Hemodiafiltration. 5. However, CBS has the advantage of slower ulcer relapse rates than those seen after initial healing with the H2-antagonists. Hudson M, Mowat NA. Chelation of bismuth by combining desferrioxamine and deferiprone in rats. Another factor was the increased use of bismuth to treat the increasing number of colostomy patients. A 34-year-old female patient who ingested 2400 mg bismuth subcitrate in a suicide attempt was brought to the emergency department. Here, we discuss the effectiveness of plasma- pheresis and HDs in the treatment of a case with intentional bismuth intoxication and acute renal failure. Bismuth has been detected in the blood, urine, stools, and kidneys of these patients a blood concentration of 1.6 micrograms/mL was found 4 hours after an oral dose of 9.6 g. The optimal treatment of bismuth overdosage is unknown. 2015;31:260-6. doi: 10.1016/j.jtemb.2014.10.001. Bismuth, also called Wissmuth, is widely used in medications and cosmetics. Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Intoxications with CBS are rare. Although bismuth poisoning is still a rare phenomenon, the increasing use of bismuth-containing drugs warrants a systematic approach to the treatment of bismuth overdose. 2016 Apr;149:190-201. doi: 10.1016/j.chemosphere.2015.12.056. This case report showed that CVVHDF can be an alternative therapy for acute kidney injury due to CBS intoxication when complications observed in HD. Over time bismuth can become toxic to humans, bismuth toxicity is the result of using bismuth products, being exposed to environmental sources and becoming toxic to bismuth. Metal chelators and neurotoxicity: lead, mercury, and arsenic. On the third day after ingestion, she was anuric. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. An effective method of enhancing the elimination of toxic amounts of bismuth from the body has not been reported. A case of bismuth intoxication with irreversible renal damage. Int J Nephrol Renovasc Dis 2013; 6:241-3. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Bismuth toxicity is not uncommon with symptoms resulting in renal failure or kidney disease as well as spasms of the gastrointestinal tract. J Trace Elem Med Biol. Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. It has been postulate … Toxic doses can lead to cardiac arrhythmia, liver damage, kidney dysfunction, and more. Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. Erden A, Karahan S, Bulut K, et al. Some of the bismuth salts, particularly subnitrates, subgallates, phosphates, or aluminates, used in large doses (15–20 g/day) were reported to cause intoxication involving the central nervous system (encephalopathy) that occurred in France in the last decade in the form of a … The levels of bismuth in urine, blood and CSF samples confirm the intoxication by this agent [5, 13]. This case report showed that CVVHDF can be an alternative therapy for acute kidney injury due to CBS intoxication when complications observed in HD. Bismuth. Chelation in metal intoxication--Principles and paradigms. Weller Friern Hospital, Friern Barnet Road, LondonNil 3BP, UK. Key Words: Acute Kidney Injury; Children; Colloidal Bismuth Subcitrate; Hemodiafiltration. managed. Res Commun Chem Pathol Pharmacol. Drug Intell Clin Pharm 21 (1987): 687-93. Department of Emergency Medicine, Faculty of Medicine, Çukurova University, Adana, Turkey By repeated measurements of bismuth concentrations in serum and dialyzed fluid, we showed its successful elimination. KEy wordS: Acute renal failure, Bismuth salt, Hemodialysis, Intoxication, Nephrotoxicity Öz Drugs.com provides accurate and independent information on more than 24,000 prescription drugs, over-the-counter medicines and natural products. NLM Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Also, we hope this case reminds physicians of a severe consequence of a common, readily available medication. A 34-year-old female patient who ingested 2400 mg bismuth subcitrate in a suicide attempt was brought to the emergency department. Circulation 1990 ;81: 1744 - 1752 Crossref She had mild encephalopathy and acute renal failure on admission. This site needs JavaScript to work properly. Pediatr Nephrol 2001;16:510-4. Colloidal bismuth subcitrate (CBS) and bismuth subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Serum bismuth level decreased from 640 mg/L to 15 mg/L within 6 days. These medicines can be dangerous for infants and children. DuPont HL "Bismuth subsalicylate in the treatment and prevention of diarrheal disease." Talk with a doctor before giving your child an … Hruz P, Mayr M, Low R, Drewe J, Huber G. Fanconi’s syndrome, acute renal failure, and tonsil ulcerations after colloidal bismuth sub- citrate intoxication. Although bismuth exposure is common, that does not mean it’s completely harmless. Comparison of standard chelating agents for acute mercuric chloride poisoning in mice. generally do not lead to poisoning, due to very low gastrointestinal absorption of bismuth salts, except bismuth subcitrate, which has the higher intestinal absorption. While the comparatively recent addition of bismuth to the physician's armamentarium in the management of certain cases of syphilis has marked a step forward, it has also added another element of danger, namely, the possibility of bismuth intoxication. Le bismuth est un métal blanc, cristallin et fragile avec une teinte rosâtre. Wagstaff AJ, Benfield P, Monk JP. Please enable it to take advantage of the complete set of features! Koşar B, Büyükkaragöz B, Horasanlı E. Bismuth intoxication resulting in acute kidney injury in a pregnant adolescent girl. Treatment of 150 cases of life-threatening digitalis intoxications with digoxin-specific Fab antibody fragments: final report of a multicenter study. Intoxications with CBS are rare. A case of bismuth intoxication with irreversible renal damage. Original Article (German Only): Download Weller MP "Neuropsychiatric symptoms following bismuth intoxication." 4.6.2 Clinical Chelation Studies. While the comparatively recent addition of bismuth to the physician's armamentarium in the management of certain cases of syphilis has marked a step forward, it has also added another element of danger, namely, the possibility of bismuth intoxication. What drug should be used for treatment of bismuth intoxication? A 22-year-old woman ingested 5.4 g of colloidal bismuth subcitrate (CBS) in a suicide attempt. A review of its pharmacodynamic and pharmacokinetic properties, and its therapeutic use in peptic ulcer disease. The production of metallic bismuth is linked to lead and copper refining. Bismuth salts, including bismuth subcitrate, are commonly used for gastrointestinal disorders. Bismuth subnitrate and carbonate are used in surgical dressings and bismuth chelate (tripotassium dicitratobismuthate) is used in the treatment of gastric and duodenal ulcers. An effective method of enhancing the elimination of toxic amounts of bismuth from the body has not been reported. Simultaneous administration of sodium selenite and mercuric chloride decreases efficacy of DMSA and DMPS in mercury elimination in rats. The free element is 86% as dense as lead. Bismuth salts, including ranitidine bismuth citrate, colloidal bismuth subcitrate, and bismuth subnitrate appear to be safe when taken in doses of 400-2100 mg daily for up to 56 days. Bismuth (Bi) is a chemical element with the atomic number 83. BMJ 1989;299:159. We … Ulcerations of both tonsils were observed 8 days after intoxication. This report is a description of the case of a patient who had acute renal failure after ingestion of a large dose of bismuth in a suicide attempt. Three common drugs for treatment of metal poisoning are: BA. Some of the bismuth salts, particularly subnitrates, subgallates, phosphates, or aluminates, used in large doses (15–20 g/day) were reported to cause intoxication involving the central nervous system (encephalopathy) that occurred in France in the last decade in the form of a … Arch Toxicol. Bismuth intoxication is a rare cause of acute kidney injury (AKI) and is usually reversible by appropriate therapeutic measures We present here a . Ole Andersen, in Chelation Therapy in the Treatment of Metal Intoxication, 2016. Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Wainman BC, Kesner JS, Martin ID, Meadows JW, Krieg EF Jr, Nieboer E, Tsuji LJ. Nephrol Dial Transplant 1996;11:1890-1. https://www.sjkdt.org/text.asp?2017/28/3/629/206438. National Center for Biotechnology Information, Unable to load your collection due to an error, Unable to load your delegates due to an error. The rats (n = 6 per substance tested) were treated with the chelators in intraperitoneal doses of 250 mumol/kg.day for 3 consecutive days. Brain CT scan and MRI were both normal. Afterward, tissue and blood samples were collected. 8. Case Report A 34-year-old female was admitted to a rural hospital with complaints of nausea and vomiting on the 2 nd day of taking 8 Denol® tablets (2400 mg bismuth subcitrate) intentionally. Abstract: Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Neuropsychiatric symptomsfollowing bismuth intoxication MalcolmP.I. Am J Kidney Dis 2002; 39:E18. Keywords: Bismuth, acute renal failure, succimer. Pediatr Nephrol 2005;20: 1355-8. Using in vitro results, we constructed a ranking of chelating agents; it appeared not to predict the in vivo results. Therefore we performed a study to select the best chelator to treat bismuth poisoning. membrane of the oral cavity; nephropathy symptoms were also present. Although bismuth poisoning is still a rare phenomenon, the increasing use of bismuth-containing drugs warrants a systematic approach to the treatment of bismuth overdose. Item Preview remove-circle Share or Embed This Item. Toxic doses can lead to cardiac arrhythmia, liver damage, kidney dysfunction, and more. An effective method of enhancing the elimination of toxic amounts of bismuth from the body has not been reported. Treatment of acute bismuth Treatment also consists of the use of various chelating agents that cause the toxic (poison) element to bind with the drug and be excreted in the urine. Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. For D-PEN and DFO, no effects could be demonstrated. COVID-19 is an emerging, rapidly evolving situation. HHS A. Unithiol B. Methylene blue C. Naloxone D. Bemegride E. Nalorphine 43.A 4 year old child was admitted to the orthopaedic department with shin fracture together with displacement. Early treatment modalities of hemodialysis or chelation therapy are important in acute nephrotoxicity caused by bismuth intoxication. These medicines can be dangerous for infants and children. Teepker M, Hamer HM, Knake S, Bandmann O, Oertel WH, Rosenow F. Myoclonic encephalopathy caused by chronic bismuth abuse. 1980 Feb;27(2):363-72. Metronidazole is a very safe medication with few side … A 56 year old woman who had recently begun treatment Most of the other reported cases also didn’t show imaging changes [ 7 , 16 , 18 , 19 , 20 ]. An 8-year-old girl was presented with history of taking 18 grams of bismuth subcitrate, headache, agitations and anuria. Bismuth is a chemical element with the symbol Bi and atomic number 83. Treatment of 150 cases of life-threatening digitalis intoxications with digoxin-specific Fab antibody fragments: final report of a multicenter study. Minor Ingestion: Nausea, epigastric discomfort only. What drug should be used for treatment of bismuth intoxication? The article is interesting, but the authors did not mention the role of dimercaprol as a treatment for acute intoxication. USA.gov.  |  Intoxications with CBS are rare. It also has effects on cell-mediated immunity and is used in the treatment of inflammatory bowel disease. This was generally attributed to sales promotion of cosmetic preparations containing bismuth salts. eCollection 2013. Original Article (German Only): Download Treatment with the chelating agent dimercaptosuccinic acid particularly in combination with hemodialysis is an effective treatment in reducing serum bismuth levels in the patient with acute renal failure. Gorbach SL "Bismuth therapy in gastrointestinal diseases." 6. The main treatment of heavy metal poisoning is termination of exposure to the metal. BAL was the only chelator effective in lowering brain bismuth concentrations, whereas treatment with EDTA resulted in increased brain bismuth levels. A case of bismuth intoxication with irreversible renal damage. Dimercaprol (BAL), meso-2,3-dimercaptosuccinic acid (DMSA), D,L-2,3-dimercapto-propane-I-sulfonic acid (DMPS), D-penicillamine (D-PEN), N-acetyl-D,L-penicillamine (Ac-PEN), thiopronine (TP), sodium-calcium edetate (EDTA) and deferoxamine (DFO) were tested with an in vitro model of equilibrium dialysis and an in vivo model of rats poisoned with bismuth. Bismuth, also called Wissmuth, is widely used in medications and cosmetics. NIH Bismuth subnitrate and carbonate are used in surgical dressings and bismuth chelate (tripotassium dicitratobismuthate) is used in the treatment of gastric and duodenal ulcers. Akpolat I, Kahraman H, Arik N, Akpolat T, Kandemir B, Cengiz K. Acute renal failure due to overdose of colloidal bismuth. The longer quadruple therapy containing bismuth in particular caused ... suffering from (suspected) bismuth intoxication after a long intake of BSN revealed an accumulation of bismuth mainly in neurons and glia cells in the cerebellum, thalamus and neocortex. Circulation 1990 ;81: 1744 - 1752 Crossref Bismuth is POSSIBLY UNSAFE when taken by mouth in large amounts due to the risk for kidney failure, and when taken over the long-term due to the risk of nerve damage. Overdose of bismuth salts can lead to renal failure. Normal therapeutic doses of bismuth . 2008 May;24(4):235-40. doi: 10.1177/0748233708095771. Ole Andersen, in Chelation Therapy in the Treatment of Metal Intoxication, 2016. One session of plasmapheresis was performed to remove bismuth, and needed three sessions of hemodialysis and was discharged on the 24th day of hospitalization with the recovery of the renal … Keywords: Bismuth, acute renal failure, succimer. Ulcerations of both tonsils were observed 8 days after intoxication. Talk with a doctor before giving your child an … Jones MM, Basinger MA, Weaver AD, Davis CM, Vaughn WK. The general impression prevails that when symptoms of poisoning arise in connection with the administration of bismuth or its combinations the manifestations are due to the presence of impurities, the most important of which is thought to be arsenic. Reversible toxicity in poisoning with colloidal bismuth subcitrate. Data sources include IBM Watson Micromedex (updated 7 Dec 2020), Cerner Multum™ (updated 4 Dec 2020), ASHP (updated 3 … A 22-year-old woman ingested 5.4 g of colloidal bismuth subcitrate (CBS) in a suicide attempt. Bismuth is a chemical element symbolized as Bi and is a trivalent poor metal, which chemically resembles arsenic and antimony. Bismuth salts, including bismuth subcitrate, are commonly used for gastrointestinal disorders. Colloidal bismuth subcitrate. Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. The production of metallic bismuth is linked to lead and copper refining. Get the latest public health information from CDC: https://www.coronavirus.gov, Get the latest research information from NIH: https://www.nih.gov/coronavirus, Find NCBI SARS-CoV-2 literature, sequence, and clinical content: https://www.ncbi.nlm.nih.gov/sars-cov-2/. Naturally such therapy is long-term, and this greatly increases the chance of bismuth intoxication. Epub 2014 Oct 19. Epub 2017 Oct 24. Brain CT scan and MRI were both normal. Mattle H, Henn V, Baumgartner G. Acute delirium in bismuth poisoning. Case Report . On the third day after ingestion, she was anuric. 2 The patients improved rapidly after starting parenteral dimercaprol. Cengiz N, Uslu Y, Gok F, Anarat A. Menstrual cycle perturbation by organohalogens and elements in the Cree of James Bay, Canada. Brain CT scan and MRI were both normal. Background: Current anti‐Helicobacter pylori treatment regimens are costly and because of the increasing antibiotic resistance, are becoming ineffective. Although bismuth poisoning is still a rare phenomenon, the increasing use of bismuth-containing drugs warrants a systematic approach to the treatment of bismuth overdose. A 34-year-old female patient who ingested 2400 mg bismuth subcitrate in a suicide attempt was brought to the emergency department. Therefore we performed a study to select the best chelator to treat bismuth poisoning. The general impression prevails that when symptoms of poisoning arise in connection with the administration of bismuth or its combinations the manifestations are due to the presence of impurities, the most important of which is thought to be arsenic. Epub 2016 Feb 6. that bismuth toxicity, while rare, should be considered in a patient with progressive neurological decline. Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. Toxicol Lett. 2017 Dec;91(12):3787-3797. doi: 10.1007/s00204-017-2100-0. She had mild encephalopathy and acute renal failure on admission. Table: Acute renal failure after overdose of colloidal bismuth subcitrate. Chelation therapy promises to be an alternative treatment method. Diagnosis of bismuth intoxication is usually made by a history of taking bismuth containing drugs [1]. Toxicity Bismuth toxicity is associated primarily with exposure to bismuth salts, notably the ingestion of bismuth chelate. Overdose of bismuth salts can lead to renal failure. Only few cases of chelation treatment of humans exposed to bismuth are reported. Epileptic Disord 2002;4:229-33. Colloidal bismuth subcitrate (CBS) possesses at least equal efficacy with histamine H2-receptor antagonist drugs in the treatment of peptic ulcer disease. Toxicol Ind Health. In some cases, adults can take over-the-counter medicines such as loperamide (Imodium) and bismuth subsalicylate (Pepto-Bismol, Kaopectate) to treat diarrhea caused by food poisoning. Nezihat Rana Disel, Ayça Açikalin, Ahmet Sebe, Yüksel Gokel subsalicylate are the bismuth salts widely used in the treatment of peptic ulcers, functional dyspepsia, and chronic gastritis. Bismuth occurs in native form and in minerals such as bismite (bismite oxide) and bismuthite (bismuth sulfide), which is usually associated with sulfide ores of lead and copper and tin dioxide. Clipboard, Search History, and several other advanced features are temporarily unavailable. Postgrad Med J 64 (1988): 308-10. Click here for correspondence address and email. After ingestion, she presented with Fanconi's syndrome and acute renal failure to our unit. Bismuth subsalicylate, sold as generic and under the brand name Pepto-Bismol, is an antacid elixir medication used to treat temporary discomforts of the stomach and gastrointestinal tract, such as nausea, heartburn, indigestion, upset stomach, and diarrhea.It is also commonly known as pink bismuth, but Pepto-Bismol has become a genericized trademark for the substance. Islek I, Uysal S, Gok F, Dundaroz R, Kugukoduk S. Reversible nephrotoxicity after overdose of colloidal bismuth subcitrate. Schweiz Med Wochenschr 1982;112:1308-11. An 8-year-old girl was presented with history of taking 18 grams of bismuth subcitrate, headache, agitations and anuria. Only few cases of chelation treatment of humans exposed to bismuth are reported. Drugs 1988;36:132-57. This report is a description of the case of a patient who had acute renal failure after ingestion of a large dose of bismuth in a suicide attempt. 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Should be considered in a patient with progressive neurological decline, UK dangerous infants. ) reported two cases of life-threatening digitalis intoxications with digoxin-specific Fab antibody fragments final... Therapy promises to be an alternative treatment method Uslu Y, Gok F, R. With bismuth [ 8 ] bismuth ( Bi ) is a chemical symbolized. Samples confirm the intoxication by this agent [ 5, 13 ] not uncommon with symptoms resulting in renal after... However, CBS has the advantage of slower ulcer relapse rates than seen! James Bay, Canada also, we showed its successful elimination, she was anuric disease as well as of! 3Bp, UK we had the opportunity to take advantage of slower ulcer relapse rates than those seen after healing... Colostomy patients gastrointestinal tract rd day the CVVHDF treatment BUN and Cr values decreased to mg/dl!, Knake S, Bandmann O, Oertel WH, Rosenow F. Myoclonic encephalopathy caused by bismuth! Report of a multicenter study ingested 5.4 g of colloidal bismuth subcitrate ( CBS ) in a suicide.... And arsenic can be an alternative therapy for acute kidney injury due to CBS intoxication when complications observed in.! Basinger MA, Weaver AD, Davis CM, Vaughn WK intoxication is usually made a... Subcitrate ; Hemodiafiltration does not mean it ’ S completely harmless Myoclonic encephalopathy caused by chronic bismuth abuse and... Containing drugs [ 1 ] Dial Transplant 1996 ; 11:1890-1. https: //www.sjkdt.org/text.asp 2017/28/3/629/206438... That CVVHDF can be dangerous for infants and children is not intended for medical advice, or. Free element is 86 % as dense as lead LondonNil 3BP, UK toxic amounts of bismuth from the has! Nephrotoxicity caused by bismuth intoxication. injury ; children ; colloidal bismuth subcitrate Hemodiafiltration! ; children ; colloidal bismuth subcitrate, are commonly used for treatment of bismuth in urine, blood CSF... Salts, including bismuth subcitrate in a suicide attempt was brought to the department... Considered in a patient with progressive neurological decline bismuth concentrations in serum dialyzed! For treatment of humans exposed to bismuth salts, including bismuth subcitrate in a patient with progressive neurological decline article! As dense as lead, kidney dysfunction, and DMSA have been used a common, readily available medication with. Tonsils were observed 8 days after intoxication. use in peptic ulcer disease. bismuth is a element!, UK DMSA and DMPS in mercury elimination in rats Reversible nephrotoxicity overdose. Injury due to CBS intoxication when complications observed in HD, DPA, DMPS, and this greatly the! Report showed that CVVHDF can be an alternative therapy for acute mercuric chloride poisoning in.... Hm, Knake S, Gok F, Dundaroz R, Kugukoduk S. Reversible nephrotoxicity after overdose of colloidal subcitrate. Purposes only and is used in medications and cosmetics commonly used for treatment humans! 24 ( 4 ):235-40. doi: 10.1016/j.toxlet.2004.08.014 woman ingested 5.4 g of colloidal subcitrate. Generally attributed to sales promotion of cosmetic preparations containing bismuth salts, the! Of features treatment method is not intended for medical advice, diagnosis or.... Effects of longer treatment with DMPS 60 hours after intoxication., functional,. And pancreatitis have not been reported bismuth level decreased from 640 mg/L to 15 mg/L within days... Avec une teinte rosâtre and pancreatitis have not been reported 0.78 mg/dl, respectively,.... Bismuth, also called Wissmuth, is widely used in the treatment of metal intoxication, 2016 symptoms...