Mineral, Vitamin, and Herbal Supplements

Calcium

It may be reasonable for patients to supplement their diet with calcium, because calcium supplementation has been shown to promote bone health and may be lacking in certain diets. Many women supplement with calcium to improve symptoms associated with premenstrual syndrome and premature bone breakdown.

However, calcium may interfere with a host of common drugs. The anesthesiologist must be aware of patients with cardiac problems who may be taking calcium channel blockers or beta-adrenergic blockers. The effects of calcium channel blockers may be affected by calcium supplementation; calcium has been shown to antagonize the effects of verapamil. In fact, calcium has recently been used in the successful management of calcium channel blocker overdose. Calcium supplementation may also decrease levels of β-blockers, leading to a greater chronotropic and inotropic presentation than would be expected.

Thiazide diuretics increase serum calcium concentrations, possibly leading to hypercalcemia as a result of increased reabsorption of calcium in the kidneys. Dysrhythmias may occur in patients taking digitalis and calcium together. The antibiotic effect of tetracyclines and quinolone and pharmacologic blood levels of bisphosphonates and levothyroxine may be decreased with calcium supplementation; these medications should not be taken within 2 hours of calcium intake.

Calcium supplementation may also affect the choice of anesthesia used in surgical procedures. Recent data suggest that propofol may have a protective effect on erythrocytes in patients with elevated calcium levels. Documenting the use of calcium by patients preoperatively may prevent many of these drug interactions.

Chromium

Chromium is an essential nutrient involved in metabolism of carbohydrates and lipids. Recently, chromium has received attention from consumers in the belief that it may improve glucose tolerance in diabetics, reduce body fat, and reduce atherosclerotic formation. These purported effects stem from chromium's effect on insulin resistance. However, the evidence regarding use of chromium for insulin resistance and mildly impaired glucose tolerance is inconclusive.

A double-blind trial with 180 patients concluded that high doses of chromium supplementation (1000 mg) may have beneficial effects on hemoglobin A _1c , insulin, cholesterol, and overall glucose control in type 2 diabetic patients. The practitioner should consider asking all diabetic patients if they supplement with chromium. Because of chromium's effects on insulin resistance and impaired glucose control, some patients will supplement with this mineral to reduce risk of cardiovascular disease. Human studies have shown decreased total cholesterol and triglyceride levels in elderly patients taking 200 μg of chromium twice daily.

Chromium is generally well tolerated; however, some patients may experience central nervous system (CNS) symptoms (e.g., perceptual, cognitive, and motor dysfunction) with doses as low as 200 to 400 μg. In addition, toxicity has been reported with chromium consumption. In one case, a woman developed anemia, thrombocytopenia, hemolysis, weight loss, and liver and renal toxicity when attempting weight loss with 1200 to 2400 μg of chromium picolinate. These problems resolved after discontinuation of chromium ingestion. A lower dose of only 600 μg was demonstrated to have resulted in interstitial nephritis in another female patient (see Table 16-1 ).

Magnesium

Magnesium plays many important roles in structure, function, and metabolism and is involved in numerous essential physiologic reactions in the human body. Supplemental magnesium has been used extensively by patients for cardiovascular disease, diabetes, osteoporosis, asthma, and migraines, although most individuals consume adequate levels in their diet. Patients with a history of these illnesses may be supplementing with magnesium and therefore should be questioned.

The most obvious anesthesia-related consideration in treating a patient taking magnesium involves its effect on muscle relaxants in the operating room (OR). The mineral can potentiate the effects of both depolarizing and nondepolarizing skeletal muscle relaxants. Therefore, it may be advisable to ask patients about their magnesium use preoperatively to avoid potential complications in the OR.

When caring for obstetric patients, the clinician must be aware of the effects of magnesium sulfate in the patient undergoing cesarean section. Duration of action of relaxant anesthetics may be affected even by subtherapeutic serum magnesium levels. Rapid inadvertent infusion of magnesium can lead to hypermagnesemia, especially during an urgent cesarean section, resulting in respiratory muscle weakness and inability to extubate safely. For this patient, an intensive care unit (ICU) stay and time will restore strength as the magnesium is cleared from the patient and will ensure a good outcome.

Magnesium may also interfere with the absorption of antibiotics such as tetracyclines, fluoroquinolones, nitrofurantoins, penicillamine, angiotensin-converting enzyme (ACE) inhibitors, phenytoin, and histamine-2 (H ₂ ) blockers. Absorption problems can be ameliorated by not taking doses of magnesium within 2 hours of these other medications. Current studies also support that intake of oral magnesium favorably affects both exercise tolerance and left ventricular (LV) function in stable patients with coronary artery disease and may be useful for high-risk surgeries in this subpopulation. Magnesium may also make oral hypoglycemics, specifically sulfonylureas, more effective when used concomitantly, thus increasing the risk of hypoglycemic episodes. Recent studies suggest magnesium supplementation for patients taking long-term proton pump inhibitors (PPIs), with the potential for hypermagnesemic or hypomagnesemic states for these patients.

Iron

In both developed and underdeveloped countries, iron deficiency is the most common nutrient deficiency. Worldwide, at least 700 million individuals have iron deficiency anemia. More than just a constituent of hemoglobin and myoglobin, iron is a key component in almost every living organism and in humans is associated with hundreds of enzymes and other protein structures. People have supplemented with iron for many reasons, including treating iron deficiency anemia, alleviating poor cognitive function in children, increasing athletic performance, and suppressing restless legs syndrome (RLS).

High concentrations of iron in the blood may worsen neuronal injury secondary to cerebral ischemia. Increased iron levels during pregnancy may lead to preterm delivery and neonatal asphyxia. These complications may occur even with normal iron intake if the patient also takes vitamin C, because high doses of vitamin C can increase iron absorption.

Iron may inhibit absorption of many drugs, including levodopa, methyldopa, carbidopa, penicillamine, thyroid hormone, captopril, and antibiotics in the quinolone and tetracycline family. Moreover, iron deficiency anemia may lead to increased risk of blood transfusion; studies have demonstrated the benefits of intravenous (IV) iron preoperatively to help decrease the risk. Some medications may decrease iron absorption and lead to decreased therapeutic levels. This includes antacids, H ₂ receptor antagonists, PPIs, and cholestyramine resin. Oral iron should not be given within 2 hours of other pharmaceuticals, to avoid alterations in drug or mineral absorption (see Table 16-1 ).

Selenium

Selenium, an essential trace element, functions in a variety of enzyme-dependent pathways, especially those using selenoproteins. Much of its supplemental efficacy results from its antioxidant properties. Glutathione peroxidase incorporates selenium at its active site, and as dietary selenium intake decreases, glutathione levels drop. Patients supplement with selenium for a variety of reasons, most notably for improvement in immune status; elderly patients may be inclined to supplement with selenium for this reason. Toxicity with selenium supplementation begins at intake greater than 750 μg/day and may manifest as garliclike breath, loss of hair and fingernails, gastrointestinal (GI) distress, or CNS changes. Few interactions with other pharmacologic agents have been found.

Zinc

Zinc deficiency was first described in 1961, associated with “adolescent nutritional dwarfism” in the Middle East. Zinc deficiency is thought to be quite common in infants, adolescents, women, and elderly populations. The most well-known use for zinc supplementation is in treatment of the common cold, caused principally by the rhinovirus. Patients self-medicating with zinc supplements may inadvertently overmedicate with zinc. Signs of zinc toxicity include anemia, neutropenia, cardiac abnormalities, unfavorable lipid profiles, impaired immune function, acute pancreatitis, and copper deficiency. Zinc supplements may interfere with the absorption of antibiotics such as tetracyclines, fluoroquinolones, and penicillamines. Zinc should not be ingested within 2 hours of antibiotics (see Table 16-1 ).

Vitamin A

The term “vitamin A” refers to a large number of related compounds, including preformed retinol (an alcohol) and retinal (an aldehyde). Vitamin A deficiency is common in teenagers, lower socioeconomic groups, and in developing countries. Furthermore, some studies indicate that diabetic patients are at an increased risk for deficiency. Vitamin A deficiency may manifest as night blindness, immune deterioration, birth defects, or decreased red blood cell (RBC) production. Purported therapeutic uses for vitamin A include diseases of the skin, acute promyelotic leukemia, and viral infections.

Retinoids are used as pharmacologic agents to treat skin disorders; psoriasis, acne, and rosacea have been treated with natural or synthetic retinoids. Moreover, retinoids are effective in treating symptoms associated with congenital keratinization-disorder syndromes. Therapeutic effects stem from their antineoplastic activity. Patients with these illnesses may be supplementing with vitamin A, and their dosages should be explored. Vitamin A may increase anticoagulant effects of warfarin, which could increase the risk of bleeding in these patients. Bleeding complications may therefore be avoided by informing the patient about this effect preoperatively.

Excess vitamin A intake during pregnancy, as well as deficiency, may lead to birth defects. Pregnant woman who are not vitamin A deficient should not consume more than 2600 IU/day of supplemental retinol. Patients using isotretinoin and pregnant women taking valproic acid are likewise at increased risk for vitamin A toxicity. Also, alcohol consumption decreases the liver toxicity threshold for vitamin A, narrowing its therapeutic window in alcoholic patients.

Vitamin B ₁₂

Vitamin B ₁₂ , the largest and most complex of all vitamins, is unique in that it contains cobalt, a metal ion. Vitamin B ₁₂ deficiency may affect almost 5% of the general adult population. B ₁₂ deficiency manifests as pernicious anemia. This syndrome includes a megaloblastic anemia as well as neurologic symptoms. The neurologic manifestations result from degeneration of the lateral and posterior spinal columns and include symmetric paresthesias with loss of proprioception and vibratory sensation, especially involving the lower extremities. The most documented use of vitamin B ₁₂ is in the treatment of pernicious anemia. Many of the neurologic, cutaneous, and thrombotic clinical manifestations have been successfully treated with oral or intramuscular (IM) cyanocobalamin.

The common anesthetic nitrous oxide (N ₂ O) inhibits vitamin B ₁₂ –dependent enzymes and may produce clinical features of deficiency, such as megaloblastic anemia and neuropathy. Some experts believe that vitamin B ₁₂ deficiency should be ruled out before N ₂ O use because many elderly patients will present to the OR with this deficiency. The colchicines as well as metformin, phenformin, and zidovudine (AZT) may decrease the levels of vitamin B ₁₂ . H ₂ receptor blockers and PPIs may decrease absorption of vitamin B ₁₂ from food, but not absorption from dietary supplements (see Table 16-2 ).