False hyperchloremia in a bromide intoxication

A false hyperchloremia in a patient with a history of depression suspected bromide intoxication. The diagnosis was confirmed by an increased bromide concentration > 20 mmoL.L-1. Rehydration was effective and allowed to decrease bromide concentration. In conclusion, hyperchloremia associated with a negative anion gap is a clue to the diagnosis.     

False hyperchloremia in bromism

Plasma chloride concentration measured by an ion-specific electrode can be interfered by other ions. The authors experienced a case of phantom limb pain with a marked hyperchloremia (251mEq·l ^–1) which was measured by the ion-specific electrode method. The patient was diagnosed as bromide intoxication due to chronic ingestion of analgesic tablets which contain bromvalerylurea. A toxic level of plasma bromide concentration supported the diagnosis. Elevated plasma chloride and bromide concentrations were normalized in three weeks after discontinuation of the analgesic intake.Laboratory study revealed that fluoride ion did not affect chloride concentration measured by an ion-specific electrode. Bromide and iodide ions, however, interfered with the electrode and produced a large overestimation of chloride concentration.Hyperchloremia should be interpreted carefully when chloride was measured by an ion-specific electrode method.(Yamamoto K, Kobayashi H, Kobayashi T, et al.: False hyperchloremia in bromism. J Anesth 5: 88–91, 1991)     

Serum electrolyte patterns in end-stage renal disease

The charts of 70 successive patients presenting for dialysis therapy for end-stage renal disease (ESRD) were evaluated for their serum electrolyte values. The "classical" pattern of low total CO2 (tCO2), elevated anion gap ("delta"), and normal chloride was found in a minority of patients (14 of 70, or 20%). Hyperchloremia was noted in 46%; in 21 patients (30%), this was associated with a normal delta and in 11 (16%), hyperchloremia was accompanied by an elevated delta. Fourteen patients (20%), most with diabetic nephropathy, had normal serum electrolytes. Patients with chronic glomerulonephritis had a hyperchloremic pattern as often as not, and two of four patients with interstitial nephritis demonstrated hyperchloremia without an elevated delta. We conclude that the previously held thesis that hyperchloremia is a rare or absent finding by the time renal failure progresses to ESRD is no longer tenable. Furthermore, a significant minority of ESRD patients may require the initiation of dialysis at a time when their serum electrolytes are still normal.     

Elevated serum levels of bromine do not always indicate pseudohyperchloremia

Background  

We encountered a case of bromism that was found to be due to pseudohyperchloremia. Hyperchloremia is known to be able to reveal existing bromism, but the fact that bromine (Br⁻) influences chloride (Cl⁻) in assays that use ion electrode machines is not widely known.     

Can the extent of halothane debromination be predicted preoperatively?

In an attempt to predict the extent of halothane debromination, antipyrine metabolic clearance rate was measured preoperatively in 22 surgical patients, then correlated with percent hours of subsequent halothane exposure and postoperative serum bromide levels. There was a significant correlation (r = 0.78, p less than 0.001) between peak bromide level and anesthetic exposure but no correlation between peak bromide levels and antipyrine metabolic clearance rate. Thus, antipyrine is of no value for predicting the extent of halothane debromination. Mean peak bromide level 0.97 +/- 0.09 mM occurred on day 3 after anesthesia. This value is well below the psychoactive range. The data, therefore, also suggest that there is not a causal relationship between halothane biotransformation and the clinical syndrome of bromism.     

Effects of various energy substrates on the recovery of the hepatic energy level after cold storage

Effects of various energy substrates on the recovery of the hepatic energy level after 2 hour's cold storage were investigated. The following results were obtained. 1) Hepatic energy charge (EC) changed from 0.85 (normal value) to 0.42 after the end of 2 hour's cold stage. Hepatic EC recovered partially to about 0.65 due to reperfusion with the perfusate containing glucose (100 mg/dl). However, hepatic EC recovered no longer even with the perfusate containing glucose (200 mg/dl). 2) Hepatic EC recovered to almost normal value with the perfusate containing 3.3 mM alanine and glucose (100 mg/dl). In addition, the same recovery was observed with the perfusate containing 0.5mM palmitate and glucose (100 mg/dl). At the same time, increase of oxygen consumption was observed due to the addition of alanine on palmitate as compared with glucose in the perfusate. 3) No recovery was observed with the perfusate containing 1 mM palmitate and glucose. Also, more increase was observed in the oxygen consumption with the perfusate containing 1 mM palmitate than 0.5 mM palmitate. It is likely that uncoupling of mitochondria happened by high concentration of palmitate. As a result, glucose is is not sufficient for the recovery of hepatic EC after cold storage, however, physiological concentration of alanine or palmitate seemed to promote the recovery of the energy level to almost the normal level.     

Plasma hippurate in renal failure: high-performance liquid chromatography method and clinical application

We have developed a high-performance liquid chromatography (HPLC) method for assay of hippurate in plasma of patients with renal failure. Hippurate accounts, in part, for the impaired binding of drugs and metabolites to albumin and may cause other disorders in azotemic patients. The method is precise, accurate and reproducible. Among 25 patients with acute and chronic renal failure having serum creatinine in the range of 2.9-43 mg/dl (256-3,801 mumol/l), plasma hippurate ranged from 0.11 to 16.2 mg/dl (6.1-904 mumol/l). Hippurate concentration correlated moderately closely with plasma creatinine, urea and anion gap. Its curvilinear relation to the reciprocal of serum creatinine indicated a proportional decline of GFR and tubular function or the accumulation of inhibitors of the proximal tubular anion secretory pathway. The method should be useful for further studies of abnormal albumin binding as well as other disorders in azotemic patients.     

Acute salicylate intoxication after trancutaneous absorption]

Topical salicylate preparations are primarily employed as keratolytic agents in the treatment of dermatologic disorders. A case of severe salicylate intoxication in a 70-year-old man with psoriasis, treated with a topical cream containing salicylic acid, is described. After five days the patient was admitted to ICU with encephalopathy and severe acid-base disturbances (respiratory alkalosis, metabolic acidosis, increased anion gap). A plasma salicylate concentration was elevated at 695 mg/Lt. Emergent hemodialysis was accompanied by a rapid lowering of plasma salicylate concentration and resolution of metabolic acidosis. Salicylate is well absorbed by normal and diseased skin. In this patient the lack of a normal epidermal barrier greatly enhances absorption of topical salicylate. It is therefore suggested that all topical salicylate treatments should be routinely monitored with salicylate blood concentration especially during the initial few days after onset or after any changes in treatment.     

Rapid diagnosis of gram negative pneumonia by assay of endotoxin in bronchoalveolar lavage fluid.

BACKGROUND: Diagnosis of ventilator associated pneumonia can be made by quantitative cultures of bronchoalveolar lavage fluid or of protected specimen brushings, though cultures require 24-48 hours to provide results. In 80% of cases aerobic Gram negative bacteria are the cause. METHODS: A rapid diagnostic method of assessing the endotoxin content of lavage fluid by Limulus assay is described. Forty samples of lavage fluid were obtained from patients with multiple trauma requiring mechanical ventilation for a prolonged period. Pneumonia was diagnosed on the basis of clinical, radiological, and bacteriological findings, including quantitative cultures of lavage fluid. RESULTS: A relation was observed between the concentration of endotoxin in lavage fluid and the quantity of Gram negative bacteria. The median endotoxin content of lavage fluid in Gram negative bacterial pneumonia was 15 endotoxin units (EU)/ml; the range observed in individual patients was 6 to > 150 EU/ml. In patients with pneumonia due to Gram positive cocci and in non-infected patients the median endotoxin level was 0.17 (range < or = 0.06 to 2) EU/ml. An endotoxin level greater than or equal to 6 EU/ml distinguished patients with Gram negative bacterial pneumonia from colonised patients and from those with pneumonia due to Gram positive cocci. CONCLUSION: The measurement of endotoxin in lavage fluid is a rapid (less than two hours) and accurate diagnostic method. It should allow specific and early treatment of Gram negative bacterial pneumonia.     

HIGH ANION GAP METABOLIC ACIDOSIS IN SUICIDE: DON'T FORGET METFORMIN INTOXICATION—TWO PATIENTS' EXPERIENCES

Lactic acidosis is a well-recognized side effect of metformin, especially in patients with renal failure. Only a few cases of deliberate self-poisoning with metformin have been described in the literature. We report two patients who took a large dose of metformin in an attempt to harm themselves and both of them presented with severe lactic acidosis. The first patient was admitted because of taking large amounts of her father's unknown drug for suicide. Arterial blood gas showed severe metabolic acidosis with high anion gap and blood lactate level which metformin intoxication was documented. She died of multiple organ failure although we provided aggressive management including continuous renal replacement therapy. The second case, a type 2 diabetic patient, was sent to the emergency department after taking 110 tablets of metformin (500 mg). Arterial blood gas showed severe metabolic acidosis with high anion gap and blood lactate level. Hypotension and consciousness disturbance occurred later. After one session of hemodialysis, she recovered completely. In our experiences, metformin intoxication should be suspected when patients presented by wide anion gap metabolic acidosis after suicide attempt by taking drugs. Hemodialysis or continuous renal replacement should be initiated as soon as possible in addition to other supportive care.     

High anion gap metabolic acidosis in suicide: don't forget metformin intoxication--two patients' experiences

Lactic acidosis is a well-recognized side effect of metformin, especially in patients with renal failure. Only a few cases of deliberate self-poisoning with metformin have been described in the literature. We report two patients who took a large dose of metformin in an attempt to harm themselves and both of them presented with severe lactic acidosis. The first patient was admitted because of taking large amounts of her father's unknown drug for suicide. Arterial blood gas showed severe metabolic acidosis with high anion gap and blood lactate level which metformin intoxication was documented. She died of multiple organ failure although we provided aggressive management including continuous renal replacement therapy. The second case, a type 2 diabetic patient, was sent to the emergency department after taking 110 tablets of metformin (500 mg). Arterial blood gas showed severe metabolic acidosis with high anion gap and blood lactate level. Hypotension and consciousness disturbance occurred later. After one session of hemodialysis, she recovered completely. In our experiences, metformin intoxication should be suspected when patients presented by wide anion gap metabolic acidosis after suicide attempt by taking drugs. Hemodialysis or continuous renal replacement should be initiated as soon as possible in addition to other supportive care.     

Diagnosis of acid-base derangements and mortality prediction in the trauma intensive care unit: the physiochemical approach

BACKGROUND: Conventional measures such as anion gap and base deficit can be inadequate for defining and managing complex acid-base derangements. Physiochemical analysis is an alternative approach based on the principles of electroneutrality and conservation of mass, and may be more accurate for defining the presence and type of acidosis and unmeasured anions. METHODS: We retrospectively analyzed 2,152 sets of laboratory data from 427 trauma patients admitted to the intensive care unit. All data sets included simultaneous measurements of an arterial blood gas with base deficit (BD), serum electrolytes, albumin, lactate, and a calculated anion gap (AG). Physiochemical analysis was used to calculate the corrected anion gap (AGcorr), the apparent strong ion difference, the effective strong ion difference, the strong ion gap (SIG), and the base deficit corrected for unmeasured anions (BDua). Statistical analysis comparing AG and BD to the physiochemical measures was performed on all data and the subset of admission laboratory data only (n = 427). RESULTS: Unmeasured anions as defined by an elevated SIG were present in 92% of patients (mean SIG, 5.9 +/- 3.3), whereas hyperlactatemia and hyperchloremia were present in only 18% and 21%, respectively. The physiochemical approach yielded a different clinical interpretation of the acid-base status than the conventional approach in 597 (28%) of the data sets. Lactate level was more strongly correlated with the physiochemical measures of SIG (r = 0.48) and AGcorr (r = 0.47) than with the conventional measures of AG (r = 0.24) and BD (r = 0.36, p < 0.01 for all). Both admission BD and BDua were significantly elevated in nonsurvivors, and logistic regression analysis for prediction of mortality revealed an area under the curve of 0.70 for BDua (p < 0.01) versus 0.65 for BD (p < 0.01). AGcorr and SIG did not differentiate survivors from nonsurvivors in the group as a whole. However, analysis of patients with a normal admission lactate level (n = 322) demonstrated a significant difference between survivors and nonsurvivors in SIG (7 vs. 5, p = 0.009), BDua (-4.2 vs. -2.0, p = 0.004), and AGcorr (21 vs. 19, p = 0.04), whereas the conventional measures of BD and AG showed no significant discriminatory ability. CONCLUSION: Unmeasured anions are the most common component of metabolic acidosis in trauma intensive care unit patients. The physiochemical approach can significantly alter the acid-base diagnosis compared with conventional measures. The SIG, AGcorr, and BDua may be particularly helpful in predicting acid-base derangements and mortality in patients with normal serum lactate levels.     

Congenital sodium diarrhea in a neonate presenting as acute renal failure

Congenital sodium diarrhea is a rare cause of secretory diarrhea due to a defect in the sodium/proton exchanger that results in decreased sodium absorption and increased excretion in stools. We report a pre-term baby boy with a birth weight of 1.4 kg who was referred because of rapidly rising serum urea and creatinine. The initially reported high urine output was later found to be severe watery diarrhea with severe oliguria and acute renal failure. Associated findings were normal anion gap metabolic acidosis with hyponatremia that required >50 mmol/kg of sodium per day for correction and about 300 ml/kg per day of replacement fluid to correct fluid and electrolyte abnormalities. The patient continues to do well 5 months after diagnosis.     

Spurious rise in total carbon dioxide and chloride with negative anion gap after cystogram

We report a case of spurious hyperchloraemia, elevated total carbon dioxide and negative anion gap 9 days following a voiding cystourethrogram (VCU) in a patient with bladder exstrophy and obstructive uropathy. We believe that the spurious laboratory results were due to analytical interference of the absorbed iodine with the method of bicarbonate and chloride measurement. The absorbed iodine was retained in the circulation for an extended period because of associated renal impairment. Our patient was also on piperacillin which might have interfered with iodine clearance. Physicians and laboratory pathologists should be aware of this effect when interpreting laboratory results of patients who have undergone a VCU in association with obstructive uropathy and impaired renal function.     

Halothane biotransformation in anesthetists.

Serum bromide levels were measured in 115 anesthetists by use of x-ray fluorescence spectrometry. Bromide levels peaked at 184 +/- 21 micron in anesthetists regularly exposed to halothane (n = 20), at 58 +/- 4 micron in anesthetists sporadically exposed to halothane (n = 71), and at 46 +/- 3 micron in nonexposed anesthetists (n = 24). Kinetic studies were carried out in five other anesthetists after ten days of exposure to halothane. Average daily halothane concentration was 19.2 +/- 3.2 ppm; duration of exposure was 3.8 +/- 0.2 hours/day. Mean serum bromide level increased from 40 +/- 4 micron before exposure to 220 +/- 36 micron on the last day of exposure. Serum bromide half-life was 14 +/- 1.7 days. The study demonstrates that anesthetists debrominate halothane in a dose-related fashion. Serum bromide levels achieved, however, were far below those reported to result in clinical bromism.     

Acid-base and potassium disorders in liver disease

Acid-base and potassium disorders occur frequently in the setting of liver disease. As the liver's metabolic function worsens, particularly in the setting of renal dysfunction, hemodynamic compromise, and hepatic encephalopathy, acid-base disorders ensue. The most common acid-base disorder is respiratory alkalosis. Metabolic acidosis alone or in combination with respiratory alkalosis also is common. Acid-base disorders in patients with liver disease are complex. The urine anion gap may help to distinguish between chronic respiratory alkalosis and hyperchloremic metabolic acidosis when a blood gas is not available. A negative urine anion gap helps to rule out chronic respiratory alkalosis. In this disorder a positive urine anion gap is expected owing to suppressed urinary acidification. Distal renal tubular acidosis occurs in autoimmune liver disease such as primary biliary cirrhosis, but often is a functional defect from impaired distal sodium delivery. Potassium disorders are often the result of the therapies used to treat advanced liver disease.     

Absence of anion gap metabolic acidosis in severe methanol poisoning: a case report and review of the literature

Methanol poisoning in humans is characterized by a latent period with subsequent development of anion gap metabolic acidosis and blindness. We describe a patient with potentially lethal methanol ingestion as evidenced by an admission serum methanol level of 403 mg/dL and sustained serum methanol levels greater than 50 mg/dL for more than 18 hours after ingestion, despite hemodialysis therapy. That anion gap metabolic acidosis or visual impairment did not develop in this patient was attributed to documented prior ethanol ingestion (admission serum ethanol level of 158 mg/dL) and continued ethanol administration during hospitalization (sustained serum ethanol levels greater than 100 mg/dL). This case demonstrates the ability of ethanol to inhibit the metabolism of methanol to formic acid in humans. This inhibition was achieved without induction of lactic acidosis. Thus this case documents the efficacy of ethanol therapy in patients with methanol poisoning.     

Evaluation of serum anion gap in patients with HIV

BACKGROUND: The anion gap (AG) is an important tool in the evaluation of metabolic acidosis. It is affected by many variables including serum albumin and globulin concentrations. HIV patients may have lower serum albumin and higher serum globulin concentrations. We hypothesized that the AG in HIV patients may differ from that of normal controls. PATIENTS AND METHODS: We reviewed medical records of 248 stable HIV patients and compared their laboratory variables to 312 patients being evaluated for routine health maintenance in an outpatient setting. RESULTS: The average serum albumin concentration was not different in patients with HIV and normal controls (43 +/- 6 g/L vs. 45 +/- 4 g/L). The serum globulin concentration was significantly higher in the HIV patients when compared with that of normal controls (37 +/- 9 g/L vs. 28 +/- 6 g/L; p<0.05). The AG in the HIV patients was significantly lower than that of normal controls (9.4 +/- 1.9 mmol/L vs. 10.8 +/- 2.7 mmol/L; p<0.05). The slope of the regression line that describes the inverse relationship between serum globulin and AG was 0.147 mmol per g/L. Using this slope, AG could be adjusted for abnormal serum globulin levels: adjusted anion gap = anion gap + 0.147 x (globulin - 29). CONCLUSION: Our results indicate that the AG is lower in HIV patients and that this decrement may be due to the increase in serum globulin concentrations. Since a high serum AG metabolic acidosis may be masked by a deceitfully normal AG in patients with elevated serum globulin concentrations, calculation of corrected AG should be undertaken to avoid a costly delay in diagnosis and treatment.     

Metformin-associated lactic acidosis precipitated by acute renal failure

In type II diabetes treated with metformin, lactic acidosis is a rare but severe complication. Commonly patients with lactic acidosis show signs of shock, tissue hypoxia, acute hepatic or renal failure and the link between metformin therapy and lactic acidosis may be coincidental, associated or causal. Excessive plasma metformin concentrations show that lactic acidosis is due to a toxicological mechanism. The case of a 65-year-old woman with type II diabetes, in whom severe type B2 lactic acidosis secondary to metformin was precipitated by acute renal failure, is presented. The association of diuretics with non-steroidal anti-inflammatory drugs and colchicine was responsible for a volume depletion and an acute renal failure. Initial serum creatinine was 643 micromol x l(-1) and arterial blood gas analysis revealed a pH of 7.01. Aggressive volume expansion and correction of the acidosis with intravenous bicarbonate therapy failed. At the intensive care unit, calculated anion gap was 35 mmol x l(-1) (normal range 10-18) and lactate concentration was 12.4 mmol x l(-1), liver profile was normal. Prolonged haemodialysis using bicarbonate dialysate resulted in a favourable outcome. Toxicology confirmed retrospectively the presence of a plasma concentration of metformine of 20 mg x l(-1) (normal <2). One month after this episode she has made a recovery of tubular necrosis, although no longer prescribed metformin. Metformin should be temporally stopped when acute renal failure occurs or is anticipated; patient with acute renal failure and high calculated anion gap should benefit from lactate measurements. Early bicarbonate haemodialysis is an adequate treatment of lactic acidosis caused by accumulation of metformin associated with acute renal failure     

Recurrent severe anion gap metabolic acidosis secondary to episodic ethylene glycol intoxication

Acute ethylene glycol toxicity and its attendant metabolic derangement is a well described clinical entity. Recurrent severe anion gap metabolic acidosis consequent to episodic ingestion of ethylene glycol has not been previously reported. We present a patient who developed severe anion gap metabolic acidosis with no osmolar gap and hypokalemia, consequent to episodic ethylene glycol ingestion. Modest artifactual elevation of the serum lactic acid level and rapid response to intravenous bicarbonate infusion may serve as diagnostic clues. Consideration of these aberrant features should be included in the clinical assessment of severe anion gap metabolic acidosis.