Alcoholic Ketoacidosis Research Articles

Differences in metabolic and hormonal milieu in diabetic- and alcohol-induced ketoacidosis

Purpose: Diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) are two medical emergencies characterized by elevated total ketone body concentration. We aimed to determine differences in pathogenesis of ketoacidosis and its metabolic consequences by comparing both at presentation and during treatment, the different metabolic products and hormones involved in the ketoacidotic state. Materials and Methods: We studied 12 patients with DKA and 8 patients with AKA. On admission and every 4 hours for 24 hours during treatment, samples were drawn for determination of serum ketone bodies, lactate and pyruvate, insulin, and counterregulatory hormones (glucagon, cortisol, growth hormone, and catecholamines). Results: At presentation, with a similar β-hydroxybutyrate concentration, patients with DKA had a higher plasma glucose (32 mmol/L vs. 6.6 mmol/L), lower β-hydroxybutyrate/acetoacetate ratio (3:1 vs. 7:1), and a lower lactate/pyruvate ratio (11:1 vs. 19:1) than patients with AKA (all, P < .01). The mean time to resolve ketoacidosis in patients with AKA (6 ± 1 hour) was significantly shorter than in patients with DKA (16 ± 2 hours). At presentation, the mean insulin concentration in patients with DKA and AKA were similarly decreased (7.8 ± 2 and 10.3 ± 3 μU/mL, P = not significant [NS]).The mean glucagon level before therapy was 203 ± 15 pg/mL and 188 ± pg/mL for patients with DKA and AKA, respectively (P = NS). Levels of cortisol, growth hormone, and epinephrine at presentation and during the first 8 hours of treatment were higher in patients with DKA; however, the difference in these values did not reach statistical significance. During therapy, levels of counterregulatory hormones declined at similar rates and returned to normal values after resolution of ketoacidosis. Conclusions: Our results indicate that, in addition to a history of diabetes or alcoholism, patients with DKA and AKA differ in their metabolic parameters more than in their hormonal profile. The metabolic profile of DKA is characterized by a higher plasma glucose concentration, and lower β-hydroxybutyrate to acetoacetate and lactate to pyruvate ratios compared with patients with AKA. The initial hormonal profile in both ketoacidotic states is characterized by similarly decreased insulin levels and elevated levels of counterregulatory hormones. Copyright © 2000 by W.B. Saunders Company

Beta-Hydroxybutyric Acid—An Indicator for an Alcoholic Ketoacidosis as Cause of Death in Deceased Alcohol Abusers

We analyzed the postmortem blood of a total of 100 fatal cases for beta-hydroxybutyric acid (BHBA). In 25 cases of sudden and unexpected death of alcoholics we found pathologically increased levels of BHBA of 1260 to 47200 (median 8000) micromol/L. This led us to the diagnosis of an alcoholic ketoacidosis (AKA) as cause of death in these cases. The control group of 69 postmortem cases revealed that BHBA concentrations below 500 can be regarded as normal, and values up to 2500 micromol/L as elevated. Our study shows that BHBA values over 2500 micromol/L could lead to death, if no medical attention is sought. During storage we did not find any indication of postmortem formation or decomposition of BHBA in blood in vitro or in the corpses. In our opinion, BHBA should be considered the diagnostic marker of choice for the postmortem determination of alcoholic ketoacidosis (AKA) as the cause of death. The classical indications of such deaths are: unexpected death of a chronic alcoholic; none or only traces of ethanol in the blood; increased acetone blood concentration; and neither autopsy, histology, microbiology, nor toxicology reveal the cause of death. In six further cases a diabetic ketoacidosis (DKA) was diagnosed as the cause of death.

Alcoholic ketoacidiosis: a cause of sudden death of chronic alcoholics

In forensic medicine we often deal with cases of sudden death of chronic alcoholics from various aspects; above all we must establish the immediate cause of death. Most of the time the cause of death becomes clear from autopsies, histological, alcoholimetric and toxicological tests, but in a smaller number of cases it remains indeterminate even after these procedures. In our study we attempted to establish whether these cases of sudden death could be cases of alcoholic ketoacidosis. We studied 30 cases of sudden death of chronic alcoholics, for all of which autopsies, histological, alcoholimetric and toxicological tests had been performed, and for which we determined the β-hydroxybutyrate concentration in bodily fluid samples (blood, urine, cerebrospinal fluid and vitreous humour). In the group with indeterminate cause of death (seven cases) the average measured concentration of β-hydroxybutyrate in the blood, urine and vitreous humour was at least ten times higher than the concentrations in the group with clear causes of death, while the concentration of β-hydroxybutyrate in the cerebrospinal fluid did not differ significantly between the two groups.

Reversible myocardial dysfunction in a patient with alcoholic ketoacidosis: A role for hypophosphatemia

A 39-year-old-woman had alcoholic ketoacidosis complicated by reversible life-threatening myocardial dysfunction. This complication occurred a few hours after correction of acidosis in association with severe hypophosphatemia. A marked improvement in clinical, echocardiographic, and hemodynamic features was associated with the normalization of the serum phosphorus level. This case illustrates a rare complication of hypophosphatemia, emphasizing the need for emergency physicians to consider this metabolic disorder in the treatment of patients with alcoholic ketoacidosis. The pathogenesis of hypophosphatemia in alcoholic ketoacidosis, its potential role in myocardial dysfunction, and its therapeutic implications in emergencies are discussed.

Alcoholic Ketoacidosis at Autopsy

Total ketone bodies (acetone, acetoacetate, and beta-hydroxybutyrate) were measured in 105 medicolegal autopsies (71 non-alcoholics, 22 chronic alcoholics, and 12 diabetics) using a coupled enzymatic head-space gas chromatographic method. Samples included vitreous humour, pericardial fluid, and blood from the femoral vein, inferior vena cava (IVC), superior vena cava (SVC), and aorta. Vitreous ketone levels showed good correlation with blood and pericardial fluid levels, suggesting that vitreous could be used as an alternative autopsy specimen for this analysis. This opens up the possibility of using simpler clinical laboratory methodologies which cannot be applied to autopsy blood due to hemolysis. In 71 non-alcoholics (age 18 to 96, median 67) total ketones (mM/L) were: vitreous 0.19 to 3.35, median 0.49; pericardial fluid 0.02 to 1.54, median 0.35; femoral blood 0.23 to 8.08, median 1.00; aortic blood 0.25 to 9.96, median 0.90; IVC blood 0.30 to 6.49, median 1.27; SVC blood 0.32 to 6.00, median 1.07. Eleven outliers (> 2.5 mM/L in femoral blood) mostly had prolonged illness prior to death. The 22 alcoholics (age 36 to 83, median 62) included four extreme outliers with femoral blood total ketone levels of 129.9 (also diabetic), 39.4 (no anatomical cause of death), 38.5 (suicidal hanging), and 18.6 (hypothermia), suggesting that while alcoholic ketoacidosis may be a previously overlooked potential cause of death, interpretation must be guarded and made within the total case context. The other 18 alcoholics had ketone levels not statistically different from non-alcoholics, suggesting that ketoacidosis is a significant factor in at most a small minority of alcoholic deaths. Three of 12 diabetics had extreme elevations of femoral blood ketone bodies: 87.5, 20.4, and 17.4 mM/L. Measurement of ketone bodies in vitreous humour or pericardial fluid using clinical laboratory methodologies is recommended in unexplained deaths in chronic alcoholics as well as diabetics.

Changes in Insulin Secretion during the Treatment of Severe Alcoholic Ketoacidosis

Changes in Insulin Secretion during the Treatment of Severe Alcoholic Ketoacidosis

A prospective toxicology analysis in alcoholics

A prospective and comprehensive investigation was done on 73 medico–legal autopsies in alcoholics. The results of the toxicology analyses are described. Alcohol intoxication was the cause of death in 8%, combined alcohol/drug intoxication in 15% and drugs alone in 19%. Alcoholic ketoacidosis was found to be the cause of death in 7%. Altogether toxicology analyses were necessary for determining the cause of death in 51% of the cases. In four cases the cause of death would not have been found, had this investigation not been made. It is concluded that toxicology analyses should be the rule rather than the exception in deaths in alcoholics.

Alcoholic ketoacidosis presenting with extreme hypoglycemia

A 66-year-old man with a history of chronic alcoholism presented with Kussmaul respirations following several days of fasting accompanied by vomiting, in the presence of continued ethanol intake. He was subsequently found to have a serum glucose level of <20 mg/dL and an anion gap of 36. Despite his profound hypoglycemia, he was fully alert with no obvious neurological deficits. He recovered without incident with intravenous saline, dextrose, thiamine, and antibiotics for a bacteremic pneumonia. He had no evidence of hypoxemia, hypotension, or other features of sepsis. Alcoholic ketoacidosis in the setting of hypoglycemia is discussed. If the serum glucose level is less than the anion gap, the diagnosis of alcoholic ketoacidosis should be considered.

Alcoholic ketoacidosis: Emphasis on biochemical, metabolic and quantitative aspects

A case of an elderly cachectic woman is presented to illustrate some of the important biochemical and quantitative aspects of alcoholic ketoacidosis. A point to emphasize will be that an interplay of signals related to hormonal regulation and controls exerted by the rate of turnover of ATP in hepatocytes sets the stage for ketogenesis and also limits its maximum possible rate. The severity of acidosis is a function not only of the rate of production of ketoacids, but also the ability to dispose of H+ via buffering and metabolism of ketoacid anions. A more severe degree of acidosis may be observed in a cachectic person not only because of a smaller volume of distribution of these acids, but also because of a diminished intracellular buffer capacity. The rate of removal of H+ via metabolism of ketoacid anions is. determined by the rate of turnover of ATP in consuming organs, mainly the brain and the kidney. A decreased rate of turnover of ATP in these organs will lead to the accumulation of ketoacids. Further, while ketogenesis occurs without a lag period when ethanol is the substrate, this is not matched by a rapid rate of removal as there appears to be a time lag before the brain is fully adapted to the use of ketoacids.

Alcoholic ketoacidosis associated with hyperglycaemia: A diagnostic dilemma

AbstractThe acute presentation of alcoholic ketoacidosis accompanied by hyperglycaemia is rare, but it may lead to the misdiagnosis of metabolically decompensated Type 1 (insulin‐dependent) diabetes and to inadvertent treatment with insulin. A case of alcoholic ketoacidosis is described in which recent excessive alcohol consumption was concealed by the patient, which resulted in a diagnosis of diabetic ketoacidosis. The blood glucose concentration in alcoholic ketoacidosis may be determined by the extent to which endogenous insulin secretion is suppressed and the extent of the peripheral insulin resistance induced by alcohol and the concomitant secretion of counter‐regulatory hormones.

Severe metabolic acidosis in the alcoholic: differential diagnosis and management

1. A chronic alcoholic with severe metabolic acidosis presents a difficult diagnostic problem. The most common cause is alcoholic ketoacidosis, a syndrome with a typical history but often misleading laboratory findings. This paper will focus on this important and probably underdiagnosed syndrome. 2. The disorder occurs in alcoholics who have had a heavy drinking-bout culminating in severe vomiting, with resulting dehydration, starvation, and then a beta-hydroxybutyrate dominated ketoacidosis. 3. Awareness of this syndrome, thorough history-taking, physical examination and routine laboratory analyses will usually lead to a correct diagnosis. 4. The treatment is simply replacement of fluid, glucose, electrolytes and thiamine. Insulin or alkali should be avoided. 5. The most important differential diagnoses are diabetic ketoacidosis, lactic acidosis and salicylate, methanol or ethylene glycol poisoning, conditions which require quite different treatment. 6. The diagnostic management of unclear cases should always include toxicological tests, urine microscopy for calcium oxalate crystals and calculation of the serum anion and osmolal gaps. 7. It is suggested here, however, that the value of the osmolal gap should be considered against a higher reference limit than has previously been recommended. An osmolal gap above 25 mosm/kg, in a patient with an increased anion gap acidosis, is a strong indicator of methanol or ethylene glycol intoxication.

Alcoholic ketoacidosis as a cause of death in forensic cases

Forensic pathologists are familiar with alcohol abusers, who are found dead and in whom the cause of death cannot be ascertained. In order to examine the possible role of ketoacidosis for the cause of death in this group of alcohol abusers, the concentrations of ketone bodies (acetone, acetoacetate, D-β-hydroxybutyrate) were determined in post mortem blood specimens. Determination of the ketone body concentrations were made by a coupled enzymatic head-space gas chromatographic method. The material consisted of blood specimens from 131 deceased persons and was divided into three groups: Group 1: controls, 79 cases of non alcohol abusers; group 2: 35 cases of alcohol abusers with known causes of death and group 3: 17 cases of alcohol abusers without ascertainable cause of death. The geometric means for the sum of the ketone body concentrations in blood were: controls, 109 μmol/l; alcohol abusers with known causes of death, 152 μmol/l; and alcohol abusers without known cause of death, 590 μmol/l. The limit value between the controls and the group of alcoholics with unascertainable cause of death was by logistic regression found to be 531 μmol/l (343–1224 μmol/l). The term ‘ketoalcoholic death’ is, therefore, suggested, when the measured post mortem blood ketone body concentration in an alcoholic with otherwise unknown cause of death exceeds 531 μmol/l.

Does alcoholic ketoacidosis go undetected?

AbstractObjectiveTo review the condition of alcoholic ketoacidosis.Data sourcesEnglish language literature search using Medline® for the period 1973 to 1993. A total of 34 articles, abstracts and book chapters were used.Data synthesisAlcoholic ketoacidosis has been recognised for over 50 years yet there seems to be a lack of knowledge about this condition. The patient usually abuses alcohol, and presents with nausea, vomiting and abdominal pain. Laboratory tests show an increased anion gap metabolic acidosis and electrolyte changes secondary to vomiting and dehydration. Urinalysis may be negative for ketones. The differential diagnosis is that of a raised anion gap metabolic acidosis in the setting of chronic alcohol consumption. Intravenous fluids and glucose are the mainstays of treatment.ConclusionAcutely unwell patients who abuse alcohol commonly present to the emergency department. Failure to consider alcoholic ketoacidosis may lead to inappropriate discharge.

Renal tubular dysfunction in chronic alcohol abuse--effects of abstinence.

Alcohol abuse may be accompanied by a variety of disorders of electrolyte and acid-base metabolism. The role of the kidney in the pathogenesis of these disturbances is obscure. We sought to evaluate the alcohol-induced abnormalities of renal function and improvement during abstinence and to assess the relation between renal dysfunction and electrolyte and acid-base disorders. We measured biochemical constituents of blood and renal function before and after four weeks of abstinence in 61 patients with chronic alcoholism who had little or no liver disease. On admission, 18 patients (30 percent) had hypophosphatemia and hypomagnesemia, 13 patients (21 percent) had hypocalcemia, and 8 patients (13 percent) had hypokalemia. Twenty-two patients (36 percent) had a variety of simple and mixed acid-base disorders. Twenty of these patients had metabolic acidosis, and among them, 80 percent had alcoholic acidosis. A wide range of defects in renal tubular function, with normal glomerular filtration rate, were detected in these patients. The defects included decreases in the threshold and maximal reabsorptive ability for glucose (38 percent of patients) and in the renal threshold for phosphate excretion (36 percent); increases in the fractional excretion of beta 2-microglobulin (38 percent), uric acid (12 percent), calcium (23 percent), and magnesium (21 percent); and aminoaciduria (38 percent). Seventeen patients (28 percent) had a defect in tubular acidification, and five an impairment in urinary concentrating ability. Urinary excretion of N-acetyl-beta-D-glucosaminidase and alanine aminopeptidase were increased in 41 and 34 percent of patients, respectively. The abnormalities of blood chemistry and renal tubular function disappeared after four weeks of abstinence. Transient defects in renal tubular function are common in patients with chronic alcoholism and may contribute to their abnormalities of serum electrolyte and blood acid-base profiles.

The investigation of beta-hydroxybutyrate as a marker for sudden death due to hypoglycemia in alcoholics

The purpose of this study was to determine if the ketone body β-hydroxybutyrate (beta-HBA) is a useful positive marker for sudden deaths in chronic alcoholics, thought to be due to hypoglycemia. Beta-HBA can be reliably measured in postmortem samples of vitreous humour and urine. In fatalities where there is a history of chronic alcoholism and routine investigations, including autopsy and routine toxicology, yield only a fatty liver as positive findings, a raised level of beta-HBA can be used as an indicator for alcoholic ketosis. Alcoholic ketosis is often associated with antemortem hypoglycemia. Caution should be observed in attributing the significance of ketosis exclusively to alcohol in those conditions where it would otherwise be expected (i.e. diabetic ketoacidosis and chronic starvation). A measurement of this marker of alcoholic ketosis may also help in the investigation of cases where hypothermia or alcohol withdrawal fits are suspected.

Increased Osmolal Gap in Alcoholic Acidosis

We studied a patient with alcoholic acidosis and an increased osmolal gap. Ethyl alcohol and other compounds that are known to increase serum osmolality in alcoholics were not detected. However, the levels of glycerol, acetone, and the acetone metabolites acetol and 1,2-propanediol were increased in the serum of this patient. On admission and 3 and 7 hours after admission, the combined serum osmolality of glycerol, acetone, acetol, and 1,2-propanediol accounted for 48%, 92%, and 62% of the increase in the osmolal gap above the highest normal level of 10 mOsm/kg H2O. The disappearance of the osmolal gap correlated with the correction of the acidosis and the concomitant reduction in serum glycerol and acetone levels. Elevations of endogenous glycerol, acetone, and acetone metabolite levels should now be added as causes for an increased osmolal gap in the alcoholic patient. Ingestion of toxic alcohols can no longer be assumed to be the only cause for an increased osmolal gap in alcoholic patients.

Increased osmolal gap in alcoholic acidosis

Increased osmolal gap in alcoholic acidosis

The syndrome of alcoholic ketoacidosis

purpose: To further elucidate the clinical spectrum of alcoholic ketoacidosis (AKA). patients and methods: A case series of 74 patients with AKA defined as a wide anion gap metabolic acidosis unexplained by any other disorder or toxin, including any patient with a history of chronic alcohol abuse. The setting was the Medical Emergency Department at Grady Memorial Hospital in Atlanta, Georgia, a university-affiliated inner-city hospital. results: AKA is a common disorder in the emergency department, more common than previously thought. The acid-base abnormalities are more diverse than just a wide-gap metabolic acidosis and often include a concomitant metabolic alkalosis, hyperchloremic acidosis, or respiratory alkalosis. Lactic acidosis is also common. Semiquantitative serum acetoacetate levels were positive in 96% of patients. Elevated blood alcohol levels were present in two thirds of patients in whom alcohol levels were determined, and levels consistent with intoxication were seen in 40% of these patients. Electrolyte disorders including hyponatremia, hypokalemia, hypophosphatemia, hyperglycemia, hypocalcemia, and hypomagnesemia were common on presentation. The most common symptoms were nausea, vomiting, and abdominal pain. The most common physical findings were tachycardia, tachypnea, and abdominal tenderness. Altered mental status, fever, hypothermia, or other abnormal findings were uncommon and reflected other underlying processes. conclusions: AKA is a common disorder in chronic malnourished alcoholic persons. The acid-base abnormalities reflect not only the ketoacidosis, but also associated extracellular fluid volume depletion, alcohol withdrawal, pain, sepsis, or severe liver disease. Although the pathophysiology is complex, the syndrome is rapidly reversible and has a low mortality.

Acidocétose chez une alcoolique chronique

A 37-year-old chronic alcoholic female was admitted with epigastric pain, complete anorexia, vomiting and diarrhoea. She was dehydrated, and had polypnoea. Laboratory investigations revealed severe metabolic acidosis (pH 7.14) with a major anion gap (37.4 mmol · 1 −1), and ketone bodies in blood and urine. Blood glucose concentration was 6.1 mmol · 1 −1, there was no glycosuria. Rehydration (21 · day −1 of 5 % glucose) together with sodium bicarbonate (500 ml of 1.4 % sodium bicarbonate over the first four hours) normalized the pH (7.37). The ketone bodies disappeared on the following day. During the acute illness, were found high blood levels of glucagon and low levels of insulin. The diagnosis of alcoholic ketoacidosis, the pathogenesis of which remains unknown, is discussed.

Alcoholic Ketoacidosis

Alcoholic ketoacidosis is a relatively rare condition, which may have a lethal outcome if left untreated. This review covers definition, pathophysiology, clinical manifestations, diagnostic approach and treatment. Usually, patients respond well and quickly to treatment, if it is started early in the course. Thus, mortality can be significantly reduced.