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Lanthanoids


General information

The lanthanoids form a group of elements with atomic numbers from 57 to 71, from lanthanum to lutetium. Lanthanum, cerium, and gadolinium have gained attention in the use and design of pharmaceutical drugs [ ]; lanthanum has been used in the management of hyperphosphatemia and gadolinium as a contrast agent in MRI and in cancer treatment. Gadolinium salts are covered in a separate monograph. Earlier attention was given to cerium as an antiemetic and as part of the treatment of burns combined with silver sulfadiazine. The biological properties of the lanthanoids are primarily based on their similarity to calcium. Ln 3 + ions have a high affinity for Ca 2 + sites on biological molecules and can act as either Ca 2 + inhibitors or probes. One of the major actions of Ln 3 + is to block voltage-operated calcium channels.

Generally lanthanoids salts are non-toxic, primarily because they cannot cross cell membranes and are therefore not absorbed if taken orally. However, they are toxic if given intravenously, since they can gain access to cells that express calcium channels. Acute toxicity via this route can cause a fall in blood pressure followed by cardiovascular collapse and pulmonary paralysis. Chronic toxicity is generally associated with hepatotoxicity and edema . After intravenous administration of lanthanoid salts the lanthanoids are rapidly cleared from the blood and redistributed to the tissues, primarily the liver and bone. The lighter lanthanoids initially go to the liver, where they can cause fatty liver . They then rapidly redistribute to the bone with a half-life of 10–20 days. The heavier lanthanoids accumulate in bones, where they can reside for considerable periods of time, with half-lives of several years. The toxic effects of the lanthanoids depend on the chemical form and the route of exposure.

Cerium nitrate

Cerium nitrate has broad-spectrum antibacterial activity. Combination studies with Ce(NO 3 ) 3 and silver sulfadiazine, another metal-based agent with efficacy in the treatment of burns, have shown synergistic antimicrobial interaction between the two agents, although this is ambiguous [ , ]. The combination is manufactured commercially as Flammacerium in Europe and as Dermacerium in South America.

Topical cerium nitrate leads to a firm impermeable eschar, which is leather-like in appearance with a greenish discoloration and is firmly attached to the wound. This is in contrast to the eschar formed with silver sulfadiazine, which is typically soft, moist, uneven, and macerated. The eschar formed by cerium nitrate contains deposits of calcium and insoluble pyrophosphate and carbonate salts. The resulting eschar acts as a biological dressing, forming an impermeable crust over the wound. This covering prevents both ingress and egress of bacteria from the wound, thus preventing bacterial colonization. This leaves the wound in a clean healthy state, ready to accept a skin graft. Cerium nitrate has been used with good results in individual burns units across Europe, the UK, and the USA for nearly 30 years, although the rationale for its use has changed over time.

Despite extensive clinical use of cerium, there is no unequivocal evidence of improvements in mortality in patients with burns from randomized controlled trials. Similarly, adverse reactions are not frequently reported.

Hematologic

Methemoglobinemia has been attributed to cerium nitrate [ ].

  • A 16-year-old girl with 95% third-degree burns had Flammacerium® dressings applied every day. Arterial gases were normal at the start but she had multiple episodes of de-saturation on days 4 and 5 (92% SaO 2 ). On day 6, bluish skin coloring was observed in the healthy areas of the face and hands. SaO 2 was now 94%, and was not correlated with the arterial blood gases (measured SaO 2 98%, PaO 2 12.2 kPa, FiO 2 0.3). The methemoglobin concentration was 32% (reference range 0–1.5%). She was treated with oxygen and methylthioninium chloride 1.5 mg/kg (i.e. 100 mg). The Flammacerium dressing was replaced with Flammazine. The anomalies were quickly corrected and there was no recurrence. However, she died on day 33 from multiple organ failure.

Skin

Granulomatous dermatitis has been attributed to cerium [ ].

  • A 57-year-old woman developed papulonodular lesions affecting only areas that had been burned 4 years before after treatment with topical cerium nitrate + silver sulfadiazine cream (Flammacérium). Biopsies showed sarcoidal granulomata associated with exogenous particles. Electron probe X-ray microanalysis showed a high cerium content. Screening for systemic sarcoidosis was negative. She was treated with hydroxychloroquine and after 4 months there was clinical and histological evidence of reduced infiltration.

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