Renal failure, acute metabolic acidosis

B. Other glycols (see Table 11-24). Diethylene glycol and glycol ethers are extremely toxic and may produce acute renal failure and metabolic acidosis. Calcium oxalate crystals may or may not be present. 

In animals that have acute renal failure and metabolic acidosis, the intracellular pH (pHi) of brain and skeletal muscle is normal (Arieff et al., 1977). In dogs with chronic renal failure, intracellular pH is normal in brain, liver and skeletal muscle (Mahoney et al., 1983). In patients with renal failure, intracellular pH has beeu reported to be normal in both skeletal muscle and leukocytes, as well as in the whole body (Levin Baron, 1977 Maschio et al., 1970 Tizianello et al., 1977). The pH of CSF has also been shown to be normal in both patients and laboratory animals with renal failure (Arieff et al., 1977 Mahoney et al., 1983). Thus, despite the presence of extracellular metabolic acidemia in patients or laboratory animals with either acute renal failure or chronic renal failure, the intracellular pH is normal in the brain, white cells, liver and skeletal muscle. 

Metformin is contraindicated in patients with heart failure, renal disease, hypersensitivity to metformin, and acute or chronic metabolic acidosis, including ketoacidosis. The drug is also contraindicated in patients older than 80 years and during pregnancy (Pregnancy Category B) and lactation. 

Potassium is contraindicated in patients who are at risk for experiencing hyperkalemia, such as those with renal failure, oliguria, or azotemia (file presence of nitrogen-containing compounds in the blood), anuria, severe hemolytic reactions, untreated Addison s disease (see Chap. 50), acute dehydration, heat cramps, and any form of hyperkalemia Potassium is used cautiously in patients with renal impairment or adrenal insufficiency, heart disease, metabolic acidosis, or prolonged or severe diarrhea. Concurrent use of potassium with... 

Clinical chemistry prior to death for both men revealed metabolic acidosis, acute renal and hepatic failure, skeletal muscle necrosis, and damage to other organ systems. Autolysis of viscera prevented complete characterization of lesions associated with mortality from these... 

Renal Effects. The patient described by Letz et al. (1984) (see Section 2.2.3.1) who lived for 64 hours after exposure to toxic levels of 1,2-dibromoethane had acute renal failure as evidenced by severe oliguria 24 hours after exposure and abnormal clinical chemistry values (blood urea nitrogen, creatinine, and serum uric acid). Severe metabolic acidosis was present despite two hemodialysis procedures. 

Two workers collapsed while inside a tank that was later found to contain a 0.1-0.3% EDB solution. Removed after 20-45 minutes in the tank, one man was intermittently comatose, and the other was delirious and combative. Both experienced vomiting, diarrhea, abdominal pain, and burning of the eyes and throat. Metabolic acidosis and acute renal and hepatic failure ensured. Death occurred 12 and 64 hours later, respectively, despite supportive measures. 

Five patients with metformin-associated severe lactic acidosis, seen between 1 September 1998 and 31 May 2001, have been reported (58). Two had attempted suicide. All had severe metabolic acidosis with a high anion gap and raised blood lactate concentrations. Four developed profound hypotension and three had acute respiratory failure. Three had normal preceding renal function. Three required conventional hemodialysis and two continuous renal replacement therapy. 

In contrast, published case reports and case series have provided more insight into the potential nephrotoxicity associated with COX-2-selective inhibitors. Taken together, these case reports suggest that COX-2 inhibitors, like non-selective NSAIDs, produce similar and consistent renal adverse effects in patients with one or more risk factors that induce prostaglandin-dependent renal function (that is patients with renal and cardiovascular disease and taking a number of culprit medications, such as diuretics and ACE inhibitors). Acute renal insufficiency, disturbances in volume status (edema, heart failure), metabolic acidosis, hyperkalemia, and hyponatremia have been commonly described. The duration of treatment with COX-2 inhibitors before the development of chnically recognized renal impairment ranged from a few days to 3-4 weeks. Withdrawal of COX-2 inhibitors and supportive therapy most often resulted in resolution of renal dysfunction, but in some patients hemodialysis was required (102,108-112). 

A 36-year-old long-distance truck driver took 200 ml of ethylene glycol in a suicide attempt (32). He vomited, lost consciousness, and had miosis and external ophthalmoplegia. There was a severe metabolic acidosis with a wide anion gap and many crystals in the urinary sediment. Acute oliguric renal failure required continuous hemodialysis for 6 days. A CT scan of the brain showed low-density areas in the bilateral basal ganglia, midbrain, and pons. A renal biopsy showed tubular oxalate deposits. He gradually recovered within 36 days. 

As discussed, increased blood or plasma lactate concentrations are usually caused by poor tissue perfusion in gastrointestinal diseases but may also result from acute renal failure, hepatic failure and anaerobic metabolism during endotoxemia. The clinical signs related to the disease causing the lactic acidosis are likely to overshadow the direct effects of the lactemia, such as decreased myocardial contractility (Yatani et al 1981). 

Nausea, vomiting, tinnitus, and hyperventilation are seen early in toxicity. As severity of toxicity increases, intractable vomiting, hyperthermia, hypotension, tachycardia, confusion, coma, seizures, pulmonary edema, acute renal failure, and death may occur. Hyperglycemia may be seen early, whereas hypoglycemia may occur later in toxicity. Acid-base disturbances such as respiratory alkalosis and/or metabolic acidosis may be noted. Signs and symptoms of salicylate toxicity may be noted as blood levels rise over 30mgdN. ... 

The majority of patients who acutely overdose on ibuprofen remain asymptomatic. In one retrospective study of ibuprofen overdoses, only 19% of patients developed symptoms. Abdominal pain, nausea, vomiting, lethargy, and drowsiness are the most frequently reported symptoms. In rare instances of massive acute overdose, apnea, seizures, hypotension, metabolic acidosis, renal failure, and coma have occurred. 

These acid metabolites are responsible for much of the toxicity of ethylene glycol, the clinical manifestations of which include neurological abnormalities (CNS depression in severe cases, coma and convulsions), severe metabolic acidosis, acute renal failure, and cardiopulmonary failure. The serum concentration of glycolic acid correlates more closely with clinical symptoms and mortality than does the concentration of ethylene glycol. Secause of the rapid elimination of ethylene glycol (ti/2 3 hours), its serum concentration may be low or undetectable at a time when that for glycolic acid remains elevated. Thus the determi-... 

Tissue ischemia may result from many causes in general, hypoperfusion leads to hypoxia of cells, which results in anaerobic metabolism with the attendant accumulation of organic (mainly lactic) acids. The kidneys (and brain) are especially sensitive to hypoperfusion, such that acute renal failure often is a contributing factor m the high anion gap metabolic acidosis associated with global tissue ischemia (as may occur in major trauma). 

Death. Cases of death in humans acutely exposed to airborne formaldehyde were not located. Death after the ingestion of fonnaldehyde (or a formalin solution) in humans has been reported in connection with attempted suicides. Metabolic acidosis has been noted prior to death, along with respiratory, cardiac, and renal failure autopsy revealed corrosive damage to gastrointestinal mucosa (Burkhart et al. 1990 Eells et al. 1981 Koppel et al. 1990). Increased rates of cancer-related mortality associated with occupational exposure to formaldehyde (predominately by inhalation) have been found in some epidemiological studies, but not in others (see Section 2.2.1.8 and Section 2.5). Animal studies indicate that subchronic inhalation exposure to concentrations below 20 ppm are not lethal (Feron et al. 1988 Maronpot et al. 1986 Martin 1990 Rusch et al. 1983 Saillenfait et al. 1989 Woutersen et al. 1987), but lifetime inhalation exposure to formaldehyde has been associated with early mortalities associated with... 

Metabolic acidosis with an increased SAG commonly results from increased endogenous organic acid production. In lactic acidosis, lactic acid accumulates as a by-product of anaerobic metabolism. Accumulation of the ketoacids /S-hydroxybutyric acid and acetoacetic acid defines the ketoacidosis of uncontrolled diabetes mellitus, alcohol intoxication, and starvation (see Table 51-5). In advanced renal failure, ac-cumulation of phosphate, sulfate, and organic anions is responsible for the increased SAG, which is usually less than 24 mEq/L." The severe metabolic acidosis seen in myoglobinuric acute renal failure caused by rhabdomyolysis may be caused by the metabolism of large amounts of sulfur-containing amino acids released from myoglobin. 

The elimination of citric acid was shown by many workers to be decreased in diabetic patients (B24, K18, 08, 012) thus, Otto (08) found that the amount of citrate excreted in urine during diabetic coma is only 2-10 % of the normal values. It is not established whether this hypocitraturia is related to a metabolic abnormaUty, due to the disease itself, or to the acidosis, or even to a renal failure during coma (08) it appears, however, that the magnitude in the decrease of urinary citrate is not related to the severity of the acidosis (08). One must add that, if the results of Rechenberger and Benndorf (R4) concerning the decrease of blood citrate levels are confirmed, diabetic patients present a simultaneous decrease in blood and urine citrate analogous to that found by Nordmann et al. (N17) during acute renal insuflBciency. 

Complications. The earliest complication of acute renal failure is hyperkalemia (see p 38) this may be more pronounced if the cause of the renal failure is rhabdomyolysis or hemolysis, both of which release large amounts of Intracellular potassium into the circulation. Later complications include metabolic acidosis, delirium, and coma. 

B. After 24-48 hours, when transaminase levels (AST and ALT) begin to rise, hepatic necrosis becomes evident. If acute fulminant hepatic failure occurs, death may ensue. Encephalopathy, metabolic acidosis, and a continuing rise in the prothrombin time (PT) indicate a poor prognosis. Acute renal failure occasionally occurs, with or without concomitant liver failure. 

A. Acute ingestion. Vomiting, abdominal pain, and diarrhea are common. Tachycardia, muscle weakness, and muscle spasms occur shortly after ingestion and may progress to profound muscle weakness and coma. Massive rhabdomyolysis, metabolic acidosis, and severe and intractable hypotension have been reported, resulting in death within 24 hours. Neurotoxic effects include ataxia, hypertonia, seizures and coma. Hepatitis and renal failure may occur. 

A. After an acute overdose, symptoms are typically delayed for 2-12 hours and include nausea, vomiting, abdominal pain, and severe bloody diarrhea. Shook results from depressed cardiac contractility and fluid loss into the gastrointestinal tract and other tissues. Delirium, seizures, or coma may occur. Lactic acidosis related to shock and inhibition of cellular metabolism is common. Other manifestations of acute colchicine poisoning include acute myocardial injury, rhabdomyolysis with myoglobinuria, disseminated intravascular coagulation, and acute renal failure. 

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