Renal failure metabolic acidosis with

Magnesium- and phosphate-containing preparations are tolerated reasonably well by most patients. However, they must be used with caution or avoided in patients with renal insufficiency, cardiac disease, or preexisting electrolyte abnormalities, and in patients on diuretic therapy. Patients taking >45 mL of oral sodium phosphate as a prescribed bowel preparation may experience electrolyte shifts that pose a risk for the development of symptomatic dehydration, renal failure, metabolic acidosis, hypocalcemic tetany, and even death in medically vulnerable populations. 

Diethylene glycol Highly nephrotoxic similar to ethylene glycol. Renal failure, coma, acidosis, and death have been reported In 5 patients with extensive burn Injuries after repeated dermal application. Vomiting, diarrhea, renal failure, metabolic acidosis, hepatitis, pancreatitis, coma, and death reported after Ingestion. Calcium oxalate crystals have been seen In animal studies. Molecular weight Is 106. Ethanol and fomepizole may be effective. 

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. 

A 34-year-old woman with a history of renal insufficiency induced by long-term use of cocaine developed respiratory failure and was intubated and sedated with intravenous lorazepam (65 mg, 313 mg, and 305 mg on 3 consecutive days). After 2 days she had a metabolic acidosis, with hyperlactatemia and hyperosmolality. Propylene glycol, a component of the lorazepam intravenous formulation, was considered as a potential source of the acidosis, as she had received more than 40 times the recommended amount over 72 hours. Withdrawal of lorazepam produced major improvements in lactic acid and serum osmolality. 

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. 

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. 

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. 

Cimetidine 800 mg daily was found to reduce the renal clearance of metformin in 7 healthy subjects by 27% and increase the AUC by 50%. A 59-year-old woman with type 2 diabetes taking long-term metformin 500 mg three times daily developed severe metabolic acidosis with cardiovascular collapse and acute renal failure. Three months previously she had started orlistat 120 mg three times daily, which caused chronic diarrhoea. During the 4 days before hospital admission, she was prescribed cimetidine 400 mg twice daily for her abdominal pain. The metformin-assoeiated lactic acidosis was considered to have been precipitated by the orlistat , (p.498) and cimetidine. ... 

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... 

Inpatients with high ethyleneglycol levels (>50 mg/dl), significant metabolic acidosis or renal failure, consider hemodialysis to remove ethylene glycol and its toxic metabolites... 

Normally, the sum of the cations exceeds the sum of the anions by no more than 12-16 mEq/L (or 8-12 mEq/L if the formula used for estimating the anion gap omits the potassium level). A larger-than expected anion gap is caused by the presence of unmeasured anions (lactate, etc) accompanying metabolic acidosis. This may occur with numerous conditions, such as diabetic ketoacidosis, renal failure, or shock-induced lactic acidosis. Drugs that may induce an elevated anion gap metabolic acidosis (Table 58-1) include aspirin, metformin, methanol, ethylene glycol, isoniazid, and iron. 

DKA is a positive anion gap metabolic acidosis associated with the accumulation of P-hydroxy-butyrate and acetoacetate. Lactic acidosis secondary to cardiac or renal failure, hypoxia, poor tissue perfusion, shock, or sepsis may also contribute to the anion gap in DKA. A normal anion gap (AG) is 12 2 mEq/L.The anion gap (AG) is calculated using the following formula AG = ([Na+ + K+] - [Cl- + HCO,]). In our illustrative case, the anion gap was 28, indicating severe metabolic acidosis. 

Metabolic acidosis involves a build-up of hydrogen ions in the blood, thus lowering blood pH. Under normal physiological conditions, the kidneys excrete excess hydrogen ions, and release more bicarbonate ions into the bloodstream to buffer the excess acid. However, in renal failure, or in diabetic ketoacidosis, this mechanism either fails, or is unable to compensate to an adequate extent. Hence, metabolic acidosis is usually treated with sodium bicarbonate, either intravenously (1.26% or 8.4% i.v. solution) or orally (typically 1 g three times a day). Sodium bicarbonate 1.26% intravenous solution is isotonic with plasma (and with sodium chloride 0.9%), so may be given in large volumes (1-2 L) by peripheral venous catheter to correct metabolic acidosis and provide fluid replacement at the same time. Sodium bicarbonate 8.4% may only be given by central venous catheter. 

The most serious adverse effects associated with polyethylene glycols are hyperosmolarity, metabolic acidosis, and renal failure following the topical use of polyethylene glycols in burn patients.Topical preparations containing polyethylene glycols should therefore be used cautiously in patients with renal failure, extensive burns, or open wounds. 

---