Heparin-induced hyperkalemia.

Heparin sodium is routinely used in the prophylaxis against deep venous thrombosis in medical and surgical patients. While most physicians are aware of heparin-induced thrombocytopenia and skin necrosis, the association of heparin and hyperkalemia is less well recognized. We present four cases in which the use of heparin was associated with hyperkalemia and discuss the pathophysiology. Our findings suggest that hyperkalemia can develop with the use of low-dose heparin, within seven days of initiating heparin therapy, and that patients with diabetes mellitus or chronic renal insufficiency are especially predisposed to this complication.

Essential fatty acid sufficiency does not preclude fat-soluble-vitamin deficiency in short-bowel syndrome.

Patients with extensive small-bowel resection may experience malabsorption and nutrient deficiencies. We evaluated the ability to absorb fat and fat-soluble vitamins in a short-gut patient. For 18 wk after stopping intravenous lipid, while consuming a low-lactose, low-fat diet, he exhibited no clinical manifestations of essential fatty acid deficiency (EFAD). Serum 20:4n-6 (20:4 omega-6) and 18:2n-6 fatty acid concentrations were normal, whereas the concentration of 20:3n-9 remained less than or equal to 0.1% of total serum fatty acids. Although serum vitamin A was normal, beta-carotene was undetectable despite oral supplementation. Prothrombin time was elevated until parenteral vitamin K was given. This patient has fat absorption adequate to prevent EFAD but inadequate absorption of fat-soluble vitamins. In patients with short bowel, the requirements for parenteral lipids and fat-soluble vitamins should be determined independently.

Predicting energy needs in ventilator-dependent critically ill patients: effect of adjusting weight for edema or adiposity.

Predicting energy needs in critical illness can be difficult because of uncertainties about the influence of multiple factors on energy expenditure. Understanding these components is important to avoid limiting optimal outcome by underfeeding and to avoid complications of overfeeding. Prediction strategies often use a patient's weight to estimate needs. For overweight patients, there is controversy as to whether actual or modified weight should be used in predictions. This study was designed to evaluate a proposed technique to improve the accuracy of predicting energy needs in critically ill, overweight subjects. Subjects' energy needs were predicted [with Harris-Benedict equation (HBE) and kilojoules per kilogram (KPK) strategies] by using both actual weight and an adjusted weight developed to attempt to more accurately reflect lean mass. Results were compared with measured energy expenditure determined by indirect calorimetry. Results indicated that use of actual weights in predictions for overweight subjects may lead to overfeeding. Use of adjusted weights led to more accurate energy predictions with the KPK than with the HBE strategy. Adjusted-weight strategies could explain > 45% of the variability of resting energy expenditure in subjects 130-159% of ideal body weight. Results of this study suggest that using adjusted weights with the KPK prediction strategy may be preferable for this population, particularly for patients > or = 130% of ideal body weight. This study also indicated that multiple diagnoses may not lead to increased energy requirements.

Diarrhea in tube-fed patients: feeding formula not necessarily the cause.

PURPOSE: This study of diarrhea in tube-fed patients was undertaken to determine the proportion of cases in which feeding formula is not responsible for the diarrhea, the causes other than the feeding formula, and the diagnostic approach to diarrhea in tube-fed patients. PATIENTS AND METHODS: Inpatients at the Truman Memorial Veterans Hospital who received nasoenteric feeding during the time period from October 1986 through May 1988 were eligible for this study. Of 123 patients who received nasoenteric feeding, 32 patients had documented diarrhea (greater than 500 mL per day for at least two consecutive days) and were enrolled. Three of these patients received hypertonic feeding formula, whereas the remaining 29 received isotonic feeding formula. Prospective determinations of the causes of diarrhea were performed. Laboratory tests included fecal leukocytes, stool osmolality, stool electrolytes, and Clostridium difficile toxin assay. Diarrhea was considered osmotic if the stool osmotic gap was greater than 100 mmol/L. Clinical management involved reducing or stopping the feeding formula, stopping suspected medications, or administering appropriate antibiotics. RESULTS: There were 32 episodes of diarrhea in tube-fed patients during the study period. A single cause could be specified in 29 cases. The tube feeding formula was responsible for diarrhea in only 21% of these cases. Medications were directly responsible in 61% and C. difficile in 17% of cases. Stool osmotic gap correctly distinguished osmotic from non-osmotic diarrhea in all cases. CONCLUSION: When diarrhea develops in properly tube-fed patients, the feeding formula is usually not responsible for the diarrhea. Patients receiving nasoenteric tube feeding are frequently placed on liquid forms of medications. Many medicinal elixirs contain sorbitol, which is often the cause of diarrhea in tube-fed patients. Review of the medications and determination of the stool osmotic gap are the initial diagnostic steps of highest yield.

Serum leukotriene B4 levels in patients with obstructive pulmonary disease.

Leukotriene B4 has been found to be increased in the serum of cigarette smokers and some patients with bronchial asthma, as well as in the sputum of patients with cystic fibrosis and COPD. Corticosteroids supposedly may block the formation of LTB4. To determine if the effect of CS on airway disease is by reduction in LTB4, we studied serum LTB4 levels in clinically stable patients with asthma or COPD who were treated with or without CS. The LTB4 was extracted from serum and assayed by radioimmunoassay. Serum LTB4 concentrations, expressed as the mean +/- SD, were 0.36 +/- 0.15 ng/ml in ten normal controls, 0.56 +/- 0.18 ng/ml in nine asthmatic subjects, 0.67 +/- 0.2 ng/ml in eight asthmatic subjects receiving CS, 0.81 +/- 0.19 ng/ml in seven patients with COPD, and 0.97 +/- 0.29 ng/ml in eight patients with COPD receiving CS. Serum LTB4 levels in normal controls differed significantly from all groups with COPD or asthma (p less than 0.01). Levels of LTB4 in asthmatic subjects differed from levels in patients with COPD (p less than 0.03), and levels in asthmatic subjects receiving CS differed from subjects with COPD receiving CS (p less than 0.03). Concentrations of LTB4 within either the COPD or the asthmatic groups were not lower in the patients treated with CS. We conclude that serum LTB4 concentrations are higher in COPD than in asthma or normal controls and that administration of CS is not associated with low LTB4 levels. The beneficial effects of CS in obstructive airway disease appear to be mediated by mechanisms other than reduction of LTB4.

Carcinogen-induced tissue vitamin A depletion. Potential protective advantages of beta-carotene.

Exposure to benzopyrene, an enzyme-inducing PAH carcinogen, promotes vitamin A depletion in exposed tissues. This effect is evident while on a vitamin A sufficient diet and without a decline in serum retinol. The finding of local tissue vitamin depletion without systemic depletion may have considerable implications in maintaining tissue health. While the described studies involved dietary exposure to benzopyrene, it is reasonable to extrapolate that inhalation exposure via cigarette smoke would have a similar effect in the lungs and perhaps stomach and bladder. Higher MFO enzyme activity in the lungs may have detrimental effects. Kellermann's early work identifying a higher incidence of lung cancer in those with genetically greater aryl hydrocarbon hydroxylase activity was interpreted as due to the greater formation of a reactive intermediate in the process of carcinogen metabolism. As an alternative hypothesis I suggest that those with higher enzyme inducibility may have greater carcinogen-induced vitamin A depletion. If poor tissue vitamin A nutriture potentiates the carcinogenicity of compounds such as benzopyrene, dietary or pharmacologic interventions which improve tissue nutriture could be important. The demonstrated effect of dietary beta-carotene on preventing carcinogen-induced tissue vitamin A depletion suggests one mechanism by which beta-carotene may be cancer protective. Further investigations are warranted, particularly with inhalation exposure to carcinogens and the effect of dietary beta-carotene on lung tissue nutriture.

Clinical management of short-bowel syndrome. Enhancing the patient's quality of life.

Management of patients following extensive small-bowel resection is complex. Parenteral nutrition is necessary initially because of a greatly reduced absorptive capacity. Intestinal adaptation occurs gradually and is stimulated by enteral feeding. Evaluation of specific nutrient status is essential, and supplementation may be required. The degree and consequences of malabsorption are more dependent on the anatomic location of resection than on the extent, but the outcome and eventual capacity for absorption in any given patient cannot be absolutely predicted. Even patients who do not achieve independence from parenteral nutrition receive many psychological and physiologic advantages by attaining the ability to consume some foods. Certain patients may subsist well on parenteral nutrition every other day without intravenous lipid. Such a regimen considerably reduces expense and simplifies clinical management, improving the quality of life.

Heparin-induced hyperkalemia.

Heparin sodium is an extremely useful medication with demonstrated benefit in a number of clinical settings. Physicians need to be aware of the potential complication of hyperkalemia, especially in patients with renal insufficiency or diabetes mellitus. Discontinuation of heparin therapy is necessary to reverse the suppression of aldosterone. If heparin is the cause, the hyperkalemia will resolve within 5 days.

Nutrition support of critically ill patients. Guidelines for optimal management.

Nutrition support is an important component of the management of critically ill patients. Before support is initiated, realistic goals should be established and risks and benefits considered. Initially, hemodynamic status should take precedence over nutritional status. Enteral feeding is the preferred route when the gastrointestinal tract is functioning. In most cases calorie requirements can be estimated adequately with use of the Harris-Benedict equation. Indirect calorimetry provides valuable information in patients with impending respiratory failure; withdrawing excess calories and substituting lipid calories for carbohydrate calories, if necessary, may be beneficial. Clinical response can be assessed by nitrogen balance studies and weekly measurement of weight and serum transferrin levels.

Muscarinic poisoning from medications and mushrooms. A puzzling symptom complex.

A mixture of signs and symptoms can occur with muscarinic poisoning from medications or mushrooms. Manifestations may vary even among persons who ingested mushrooms grown in the same patch and gathered at the same time. Confusion can occur if mushroom poisoning is attributed to a suspected species rather than to the toxin suggested by signs and symptoms. Accurate diagnosis depends on clinical suspicion and recognition of muscarinic manifestations, notably diaphoresis, salivation, bladder cramping, diarrhea, and difficulty with visual accommodation. Muscarinic toxicity due to medications necessitates an adjustment in drug dosage. In mushroom poisoning that produces primarily muscarinic effects, atropine is the treatment of choice.

Retinol and retinol-binding protein in lung cancer screening.

Human epidemiology studies demonstrate an inverse correlation between serum levels of vitamin A and the incidence of lung cancer. While such studies suggest that vitamin A may have a role in cancer prevention, the intent of this study was to investigate the use of vitamin A status parameters as markers for detection of occult lung cancer. In the first of two phases of this study, we established criteria for a prospective screening study. Serum levels of retinol-binding protein (RBP), zinc, retinol, and beta-carotene in lung cancer patients were compared to levels in controls. For the second phase, a prospective screening study, 100 ambulatory male cigarette smokers over the age of 45 were enrolled. Subjects were excluded if they had a known diagnosis of cancer, recent weight loss, or serum albumin less than 3.5 g/dl. Subjects with RBP less than 4.2 mg/dl and retinol less than 42 micrograms/dl were classified as high-risk; those remaining were classified as controls. A chest X-ray (CXR) was obtained on all 17 high-risk subjects and on 26 of the 83 controls. CXR was read and follow-up was performed by physicians without knowledge of this study. Lung cancer was detected in 24% (4/17) of the high-risk subset, and 4% (1/26) of the controls. These data suggest that retinol and RBP may be useful in lung cancer screening for selecting a high-risk population that warrants further examination.

Nosocomial diarrhea: beware the medicinal elixir.

An unusual case of osmotic diarrhea that persisted despite fasting led to the discovery of an unexpected source of hospital-acquired diarrhea. Numerous patients were subsequently found to have onset of diarrhea shortly after the initiation of treatment with theophylline elixir. Although theophylline can promote gastrointestinal secretion and motility, this effect should be independent of the route of theophylline administration and the stool should be characteristic of secretory rather than osmotic diarrhea. Patients taking no food orally while taking theophylline elixir continued to have osmotic diarrhea in excess of 1,000 ml/24 hr. Patients whose therapy was switched to intravenous or solid oral theophylline had resolution of diarrhea within 24 hours. The brand of theophylline elixir used was formulated with 30 gm of sorbitol per 240 mg of theophylline; thus a standard regimen of theophylline elixir was delivering four laxative doses of sorbitol daily. A cursory review revealed that many medicinal elixirs are formulated with sorbitol, despite being designated "sugar-free." When patients have osmotic diarrhea in the hospital, beware the medicinal elixir.

Glycemic index and insulin response to a liquid nutritional formula compared with a standard meal.

OBJECTIVE: To determine the glycemic index and metabolic responses to a nutritional formula, and to compare these responses to those following an oral glucose meal and a standard test meal. METHODS: Six male and six female healthy non-diabetic volunteers aged 18 to 48 years met screening examination and laboratory assessment criteria. Three test meals were administered, each containing 50 g of carbohydrate: nutritional formula (NF), standard test meal (ST) and a glucose test meal (GT). Each subject underwent the three test meals on separate days in randomized sequence. Blood samples were taken at intervals over 5 hours for determination of glucose, insulin and triglycerides. RESULTS: The glycemic index was similar for the NF (60.8 +/- 13.1) and for the ST (57.8 +/- 12.9) meals. The incremental area under the curve for glucose was similar for NF and ST, but each was significantly lower than for the GT meal. The total area under the curve for insulin was significantly greater for the NF meal than for the ST meal. The serum triglyceride responses were similar for NF and ST meals. CONCLUSION: In healthy non-diabetic subjects, the blood glucose and triglyceride responses are similar for a nutritional formula compared to an isoenergetic standard test meal. However, the insulin response differs. This information is important in managing tube-fed patients.

Spontaneous decline in exercise-induced proteinuria during a 100-mile triathlon.

To study the effect of prolonged exercise on glomerular permeability and proteinuria, we collected serial urine samples from six athletes during a 100-mile triathlon. Urine collected just before, at the midpoint of, and immediately after the race was analyzed for creatinine by an automated chemistry analyzer, pack method, and for microalbumin by radioimmunoassay. By midrace, the urinary albumin-creatinine ratio increased from the prerace mean +/- SEM of 3.5 +/- 0.5 to 38.3 +/- 11.7 mg/g. The ratio then declined to 12.5 +/- 2.7 mg/g by the end of the race (P less than .04). Similarly, the urinary albumin level increased significantly from 5.9 +/- 0.7 to 80.5 +/- 26.8 micrograms/mL by midrace, followed by a decline to 39.2 +/- 12.9 micrograms/mL. The initial increase in albuminuria was expected and reflects the increase in exercise-induced cardiac output and glomerular permeability. The subsequent decline in albuminuria and albumin-creatinine ratio, despite continued exercise, was unexpected and indicates a decrease in glomerular permeability. Further study is warranted to determine the mechanism of this apparently protective renal response to prolonged exercise.

Beta-carotene and aryl hydrocarbon hydroxylase in the rat: an effect of beta-carotene independent of vitamin A activity.

Animal models demonstrate a cancer-protective effect of vitamin A. However, human epidemiologic studies correlate the intake of the precursor, beta-carotene, rather than active vitamin A, to a reduced risk for certain cancers. This suggests that beta-carotene may have cancer-protective properties independent of its vitamin A activity. In the present rat study, effects of beta-carotene or active vitamin A on carcinogen metabolizing enzyme activity were evaluated. The activity of intestinal aryl hydrocarbon hydroxylase (AHH, EC 1.14.14.1) was higher in rats fed a purified diet supplemented with beta-carotene than in rats fed the control diet containing adequate vitamin A as retinyl palmitate (165 +/- 30 vs. 90 +/- 18 pmol/min x mg), P less than (0.05). Supplementing the control diet with retinyl acetate had no effect. This AHH-enhancing effect of beta-carotene on the activity of the intestinal mucosal enzyme was not seen on the hepatic enzyme, which is consistent with the nearly complete conversion of beta-carotene to vitamin A prior to reaching the liver. These results demonstrate an effect of beta-carotene on carcinogen metabolism which is independent of its vitamin A activity. This may help explain human epidemiologic data, and may lead to further work which would allow for prudent dietary recommendations toward a reduction in cancer risk.

Leukotriene B4 is measurable in serum of smokers and nonsmokers.

Leukotriene B4 (LTB4), an arachidonic acid metabolite released by neutrophils and macrophages, helps regulate host immune response to antigenic stimulation. LTB4 affects the chemokinesis, aggregation, and enzyme release of neutrophils and stimulates activity of cytotoxic T cells, natural killer cells, and suppressor T cells. LTB4 also has a positive affect on the margination of monocytes and macrophages in the lung in response to inflammatory stimuli. Cigarette smoking represents an inflammatory stimulus in the lung and affects (decreases) the in vitro release of LTB4 by alveolar, macrophages in comparison with that by alveolar macrophages of nonsmokers. By utilizing a sensitive and specific radioimmunoassay we have detected LTB4 concentrations in serum from smokers and nonsmokers. Furthermore, our preliminary data show mean LTB4 concentrations in the serum of smokers to be nearly 60-fold greater than those in nonsmokers, 211 (SEM 35) vs 3.6 (SEM 1.5). Because systemic quantities of LTB4 are now measurable, quantification of this immune system regulatory may be useful in evaluating inflammatory disease states.

Tissue vitamin A repletion is impaired by exposure to carcinogen.

Vitamin A appears to exert a protective effect against certain cancers. Epithelial cancers, such as those of the skin, bladder, oropharynx and respiratory tract, have the strongest association with vitamin A. These same cancers are causally associated with exposure to carcinogens such as benzo(alpha)pyrene (BP), a product of combustion found in cigarette smoke and charbroiled meat. This study was designed to determine whether BP exposure affects tissue vitamin A nutriture. Female Sprague-Dawley rats were randomized to purified diets, sufficient or deficient in vitamin A, and with or without 200 mg BP/kg feed. Rats were killed after 4 or 6 weeks. Serum, liver and lungs were assessed for vitamin A levels; trachea, stomach, small intestine and bladder were examined for histologic change. Lack of dietary vitamin A resulted in a profound decrease in vitamin A in the serum, liver and lungs (p less than .005). No histologic changes were evident in any tissues examined. Serum vitamin A was not affected by dietary BP. In vitamin-A-sufficient rats, dietary BP caused a significant decline in hepatic and lung vitamin A. In rats fed vitamin-A-deficient diets, dietary BP had no effect on tissue vitamin A. We conclude that chronic exposure to the carcinogen BP leads to tissue depletion of vitamin A, despite a vitamin-A-sufficient diet. We postulate that BP impairs tissue repletion by metabolizing incoming vitamin A rather than in situ vitamin A, since BP had no effect on tissue vitamin A levels in rats fed a diet devoid of vitamin A. This BP-induced vitamin depletion may eventually have a deleterious effect on epithelial tissue health, and may help to explain the association between vitamin A and cigarette-smoke-related cancers.

Exposure to the carcinogen benzopyrene depletes tissue vitamin A: beta-carotene prevents depletion.

Evidence in humans and laboratory animals supports a cancer-protective effect of vitamin A, but the mechanism remains unclear. While vitamin A deficiency causes squamous metaplasia, and lung cancer patients have lower vitamin A status, their serum vitamin A levels are not indicative of deficiency. We hypothesize that local enzymatic degradation of vitamin A can be induced by exposure to carcinogens such as benzopyrene found in cigarette smoke. This study was designed to determine if benzopyrene exposure depletes tissue vitamin A and whether beta-carotene might prevent the depletion. Weanling male Fischer rats were fed a nutritionally complete purified diet, supplemented with or without benzopyrene at 400 mg/kg feed or beta-carotene at 2 g/kg feed. Vitamin A content of the liver, small intestine, and serum was determined by high-performance liquid chromatography. There was no effect of benzopyrene feeding on serum retinol levels through four weeks. However, there was a decline in tissue retinol in the liver and small intestine by two weeks, with a 30% decline by four weeks (p less than 0.05). In rats fed beta-carotene, there was no effect of benzopyrene on tissue vitamin A level. These results indicate that exposure to benzopyrene induces a local tissue vitamin A depletion despite a vitamin A-sufficient diet and maintenance of serum vitamin A levels. A high intake of beta-carotene prevented the vitamin A depletion effect of benzopyrene exposure. Further studies appear warranted to determine whether some of the adverse effects of environmental carcinogens, as found in cigarette smoke, charcoal-broiled meats, and industrial wastes, might be alleviated by dietary intervention.

Comparison of serum and plasma leukotriene B4 levels in normal and asthmatic subjects.

BACKGROUND: Leukotriene B4 (LTB4) serum and plasma concentrations were reported to be higher in some asthmatic patients than in normal subjects; however, reported LTB4 concentrations in normal subjects vary widely. One study suggested that blood clotting causes the increased LTB4 concentration. OBJECTIVE: To determine whether LTB4 concentration is increased in asthmatic patients, and whether it is affected by clotting. METHODS: We studied seven normal subjects and nine clinically stable asthmatic patients. Venous blood was drawn into test tubes without additives; containing heparin; or containing heparin and cyclo- and lipoxygenase inhibitors. Cells were separated after 30 minutes. Leukotriene B4 was measured by radioimmunoassay following its extraction from serum or plasma. In three subjects, plasma was separated also at times 0 through 30 minutes. RESULTS: Serum and plasma concentrations of LTB4 in normal volunteers and asthmatic patients were similar, but the variance of LTB4 concentrations among the asthmatic patients was significantly higher than in the normal subjects. Leukotriene B4 concentrations, measured in plasma only, were significantly reduced in both asthmatic and nonasthmatic subjects in the presence of inhibitors. There was no significant difference in LTB4 concentrations between time 0 and 30 minutes, but there was considerable variability. CONCLUSIONS: We conclude that clotting is unlikely to affect serum LTB4 concentrations. Leukotriene B4 serum and plasma concentrations are not consistently increased in asthmatic patients; however, LTB4 is synthesized during and possibly after blood has been drawn. Proper handling of the specimens and probably the addition of cyclo-oxygenase and lipoxygenase inhibitors is of the utmost importance for accurate LTB4 determination.