Bismuth

Uses

Tripotassium dicitratobismuthate and bicitropeptide (a bismuth–peptide complex) are used in the eradication of Helicobacter pylori in combination with antibiotics [ ], and ranitidine bismuth citrate is used to treat peptic ulcer [ , ]. Bismuth subsalicylate is used in the treatment of mild dyspepsia, diarrhea, and peptic ulcer disease.

Bismuth salicylates are used in other intestinal diseases, such as microscopic colitis [ , ] and collagenous colitis [ ].

Bismuth oxide and bismuth subgallate are found in some topical formulations that are used for treating hemorrhoids [ ].

Bismuth subgallate is used topically as an astringent/hemostatic [ ], for example in tonsillectomy [ ]. A uniform technique of tonsillectomy, including the use of bismuth subgallate and re-assessment of the tonsillar fossae after a 3-minute observation period, reduced the incidence of primary tonsillar hemorrhage in a retrospective study of 705 children [ ]. However, in a randomized study of 204 patients the evidence for the use of bismuth subgallate as a hemostatic agent in tonsillectomy was weak [ ].

Bismuth subnitrate plus iodoform (bismuth iodoform paraffin paste) is commonly used in ear, nose, and throat surgery and in oral and maxillofacial surgery [ ].

Bismuth compounds have also been used as anticancer agents [ ].

Placebo-controlled studies

Data from 20 clinical studies in 5000 patients who had taken ranitidine bismuth citrate (200, 400, or 800 mg bd) have been reported [ ]. The incidence of adverse events was not different from that associated with placebo and was independent of dose. The most common events (> 1% of patients) were upper respiratory tract infections, constipation, diarrhea, nausea, vomiting, dizziness, and headache, the last being the only event reported by over 2% of the patients. Adverse events considered by the clinical investigator to be adverse reactions occurred with a similar frequency amongst patients given ranitidine bismuth citrate (8%), ranitidine hydrochloride (6%), and placebo (6%). The incidence of adverse reactions was greater when amoxicillin (11%) or clarithromycin (20%) were co-prescribed.

Systematic reviews

The safety of bismuth salts (ranitidine bismuth citrate, colloidal bismuth subcitrate, tripotassium dicitratobismuthate, bismuth subsalicylate, and bismuth subnitrate) used in Helicobacter pylori eradication regimens has been investigated in a systematic review of 35 randomized controlled trials in 4763 patients [ ]. Abdominal pain, diarrhea, dizziness, headache, metallic taste, nausea and/or vomiting, and dark stools were included as adverse events. There were no serious adverse events in patients taking bismuth. There was no statistically significant difference in total adverse events (RR = 1.01; 95%CI = 0.87, 1.16), adverse events that led to withdrawal of therapy (RR = 0.86; CI = 0.54, 1.37), or specific individual adverse events, with the exception of dark stools (RR = 5.06; CI = 1.59, 16).

Respiratory

There has been a single report of a lung disorder with cough, which was traced to intravenous injection of a so-called “health tonic” containing bismuth, which had resulted in bismuth-containing subpleural opacities in the lungs [ ].

Two cases of respiratory complications following the use of bismuth gallate have been reported [ ].

• A 19-month-old boy with reactive airways disease had a tonsillectomy and adenoidectomy and bismuth-coated sponges were used for hemostasis. Excessive bleeding was not reported. In the recovery room he developed difficulty in breathing, and required oxygen followed by bronchodilators and deep suctioning. A chest X-ray showed speckled opacities throughout the lung fields and in the oropharynx and nasopharynx, probably due to aspiration of bismuth particles. He went on to develop a pneumonitis.

• An 8-year-old girl with asthma underwent tonsillectomy and adenoidectomy; hemostasis was performed with bismuth-adrenaline paste. A small amount of bismuth was noted in the endotracheal tube before extubation, and in the recovery room she developed respiratory difficulty associated with nasal flaring and sternal retraction. A chest X-ray showed aspirated radio-opaque material outlining the tracheobronchial tree and early pulmonary infiltrates.

Both patients had a history of refractory airway disease that put them at risk of respiratory complications after bismuth aspiration. Fortunately neither developed any serious respiratory compromise immediately after aspiration or required intubation.