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Treatment of a 7-week-old black male who had proximal tubular acidosis with large doses of bicarbonate did not achieve correction of the acidosis and was accompanied by diarrhea. Addition of indomethacin therapy (2 mg/kg/day) was followed by correction of the acidosis and allowed a decrease in the dosage of alkali.
Hypokalemia and lactic acidosis developed following correction of respiratory acidosis in a 5-year-old child who presented with respiratory failure secondary to severe asthma and treated with theophylline, inhaled albuterol, and parenteral methylprednisolone. Calculation of the "anion gap" that provided the clue to presence of lactic acidosis was confirmed by the measurement of serum lactate level.
D-Lactic acid can accumulate in blood in some patients with intestinal failure, leading to a clinical syndrome of severe acidosis and encephalopathy. The possible impact of parenteral nutrition on its clinical course has not been established. One patient with a severe short-bowel syndrome supported by long-term parenteral nutrition who suffered repeated episodes of ataxia and disorientation associated with elevated serum levels of D-lactate was studied. Results demonstrated no impact of glucose- vs lipid-based parenteral nutrition formulations on total acid production or serum D-lactic acid levels, increased serum D-lactate levels during administration of neomycin, but prompt resolution of both acidosis and clinical symptoms with discontinuation of oral intake. This study confirms the findings of other investigators that D-lactic acidosis may be a significant, heretofore unappreciated complication in patients with severe short-bowel syndrome, and that prompt resolution may be effected with abrupt discontinuation of oral intake. Furthermore, the present study suggests neither a detrimental nor a beneficial effect of parenteral nutrition on this syndrome.
The authors report a case of severe lactic acidosis in a 3-year-old boy, after 20 days of total parenteral nutrition without vitamin supplementation. This child with acute lymphoblastic leukemia underwent a period of severe refractory lactic acidosis (pH between 6.81 and 7.00 and a serum lactate level up to 38 mmol/liter) leading to cardiac arrest. After the initial resuscitation and the subsequent treatment of shock and vitamin K deficiency, acute peritoneal dialysis was instituted to correct the severe lactic acidosis. Initial low plasma thiamine levels confirmed the diagnosis of thiamine deficiency. An associated transient pancreatic dysfunction was also noted. The patient's overall course with thiamine replacement therapy led to a complete recovery within 5 days and no sequelae were noted after 12 months.
We report a case of hypokalaemic quadriplegia with acute respiratory failure and life-threatening cardiac arrhythmias in a 26-year-old woman who was diagnosed to have distal renal tubular acidosis. She had persistent metabolic acidosis with severe hypokalaemia and required mechanical ventilation and potassium replacement. The anaesthetic implications of renal tubular acidosis are also discussed.
We report the seventh case of autosomal recessive inherited mitochondrial myopathy, lactic acidosis, and sideroblastic anemia The patient, a product of consanguineous Persian Jews, had the association of mental retardation, dysmorphic features, lactic acidosis, myopathy, and sideroblastic anemia. Muscle biopsy demonstrated low activity of complexes 1 and 4 of the respiratory chain. Electron microscopy revealed paracrystalline inclusions in most mitochondria. Southern blot of the mitochondrial DNA did not show any large-scale rearrangements. The patient was found to be homozygous for the 656C-->T mutation in the pseudouridine synthase 1 gene (PUS1). Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia is an oxidative phosphorylation disorder causing sideroblastic anemia, myopathy, and, in some cases, mental retardation that is due to mutations in the nuclear-encoded PUS1 gene. This finding provides additional evidence that mitochondrial ribonucleic acid modification impacts the phenotypic expression of oxidative phosphorylation disorders.
Coma and profound metabolic acidosis early in acute paracetamol poisoning have been described in three patients. Of five further patients (four female, one male, aged 17-80 years) with severe poisoning (plasma paracetamol concentration greater than 800 mg/l, 4-12 h postingestion), four were deeply unconscious on admission and two had a severe metabolic acidosis. Signs of hepatorenal damage were minimal and no additional poisons were detected except salicylates (plasma concentration 290 mg/l) in one instance. Plasma paracetamol half-lives were prolonged (median 9.4 h, range 4.8-39 h) and one patient sustained massive hepatic damage and a further patient died despite treatment with intravenous acetylcysteine. Paracetamol poisoning, when associated with exceptionally high plasma concentrations, can give rise to coma and metabolic acidosis in the absence of hepatic failure or other drugs. Although unusual, other such presentations may not have been recognized because a toxicology screen was not performed.
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.
OBJECTIVE: To report a child who developed shock, loss of consciousness, and metabolic acidosis following an ibuprofen overdose. CASE SUMMARY: A 6-year-old boy with no prior medical problems ingested approximately thirty 200-mg tablets of ibuprofen. The patient developed shock, coma, and metabolic acidosis. He was treated successfully with intubation and mechanical ventilation, fluid resuscitation, and decontamination with activated charcoal. The patient was discharged without any clinical sequelae. DISCUSSION: Serious adverse complications following ibuprofen overdose have been reported rarely in children. We reviewed literature pertaining to the etiology, pharmacology, pathophysiology, and management of complications following ibuprofen overdoses, as well as other case reports. CONCLUSIONS: Coma, metabolic acidosis, and shock were noted in a child who ingested a large quantity of ibuprofen. These complications have been described rarely in children. We attribute his favorable clinical outcome to early and aggressive intervention consisting of tracheal intubation, fluid resuscitation, and decontamination with activated charcoal. Although ibuprofen overdoses are usually benign, healthcare professionals should be aware of the various potentially serious complications that may occur.
OBJECTIVE: To describe a patient with neutropenic fever complicated by hyperglycemia, lactic acidosis, and fatal myocardial failure associated with clozapine therapy. CASE SUMMARY: A 37-year-old Ashkenazic Jewish man was admitted for agranulocytosis and fever, which developed after 11 weeks of clozapine monotherapy for drug-resistant schizophrenia. Complete blood counts and a routine serum chemical analysis had been normal before the treatment was initiated, and remained within normal limits during the first 10 weeks of the treatment. On the day of admission, the patient deteriorated rapidly and developed extreme hyperglycemia, severe lactic acidosis, recurrent cardiac arrest, cardiogenic shock, and coma. He died 36 hours later despite intensive treatment. DISCUSSIONS: Clozapine intake reduced fatal aganulocytosis, associated with hyperglycemia, lactic acidosis, and heart failure. White blood cell count monitoring was insufficient to predict these adverse effects. CONCLUSIONS: Clozapine should be avoided in high-risk patients (e.g., the elderly, women, Ashkenazic Jews).
BACKGROUND: Myocardial infarction causes the acidification of the cellular environment and the resultant acidosis maybe arrhythmogenic. The effect of acidosis on the action of antiarrhythmic drugs, an important issue in the antiarrhythmic drug therapy after myocardial infarction, remains to be studied. METHODS: To evaluate the effect of acidosis on rectifier potassium current (Ikr) blockers, the human ether-a-go-go-related gene (HERG), which encodes IKr, was expressed in Xenopus laevis oocytes. The two electrodes voltage clamp technique was used and the experiments were performed at room temperature. RESULTS: Quinidine (10 microM) inhibited HERG tail current by 37% +/- 5% at pH7.4. The block decreased to 5% +/- 2% with extracellular pH at 6.2. Dofetilide (0.3 microM) inhibited HERG tail current by 34% +/- 3% and 1% +/- 2% at extracellular pH 7.4 and 6.2, respectively. Azimilide (10 microM) inhibited HERG tail current by 59% +/- 3% and 17% +/- 3% at extracellular pH 7.4 and 6.2. There were significant differences in the HERG inhibition by quinidine, dofetilide, and azimilide between pH 7.4 and pH 6.2 (P < .01). The drug concentration blocking 50% of current (IC50) was 5.8 +/- 0.3 microM for azimilide, 9.9 +/- 1.0 microM for quinidine, and 0.5 +/- 0.02 microM for dofetilide at pH 7.4. When extracellular pH was decreased from 7.4 to 6.2, the IC50 increased to 95.5 +/- 11.3 microM for azimilide, 203.2 +/- 15.7 microM for quinidine, and 12.6 +/- 1.2 microM for dofetilide. Unlike quinidine, dofetilide, and azimilide, there was no significant difference in the percentage of current block by amiodarone between pH 6.2 and 7.4. For amiodarone, the IC50 was 38.3 +/- 8.5 microM at pH 7.4 and 27.3 +/- 1.6 microM at pH 6.2. CONCLUSION: Our data show that the Ikr blocking effect of azimilide, dofetilide, and quinidine was attenuated at acid pH, whereas this was not the case for amiodarone. These observations may explain the efficacy of amiodarone in reducing arrhythmic death in patients after a myocardial infarction compared with other IKr blockers.
In the critically ill, metabolic acidosis is a common observation and, in clinical practice, the cause of this derangement is often multi-factorial. Various measures are often employed to try and characterise the aetiology of metabolic acidosis, the most popular of which is the anion gap. The purpose of the anion gap can be perceived as a means by which the physician is alerted to the presence of unmeasured anions in plasma that contribute to the observed acidosis. In many cases, the causative ion may be easily identified, such as lactate, but often the causative ion(s) remain unidentified, even after exclusion of the 'classic' causes. We describe here the various attempts in the literature that have been made to address this observation and highlight recent studies that reveal potential sources of such hitherto unmeasured anions.
Red blood cell carbonic anhydrase activity was studied in three children with distal renal tubular acidosis, the parents of one of the patients, and in control subjects. Although each patient had distal renal tubular acidosis as defined by an inappropriately high urine pH in the face of a systemic metabolic acidosis, hyperchloremia and a low (U-B)pCO2, they differed in that two had deafness. The deafness was inherited as an autosomal recessive mode in one and by an autosomal dominant gene in the other. Red blood cell carbonic anhydrase activity was determined in hemoglobin-free hemolysate by the esterolytic action of the enzyme on the substrate p-nitrophenyl acetate. The two isoenzymes, B and C, of carbonic anhydrase were identified using polyacrylamide disc gel electrophoresis. The red blood cell carbonic anhydrase activity of nine control children aged 2-10 years was 3.8 (3.2-5.0) units/g Hb. The values obtained from the three patients were 3.0, 3.7, and 4.36 units/g Hb. These did not differ from those of the control subjects. No abnormalities were found in the ratios of the B and C peaks or in their electrophoretic mobility.
To investigate the effects of metabolic acidosis on jejunal phosphate and glucose absorption, in vivo and in vitro transport studies were performed on weanling rats fed 1.5% NH4Cl for three days and on group pair-fed controls. Both in vivo and in vitro, acidosis significantly depressed phosphate transport without effecting glucose transport. In vitro, the decrease of phosphate transport was due to a depression of sodium-phosphate cotransport, but not of sodium independent phosphate transport. This corresponded to a significant increase of the Km of sodium-phosphate cotransport with no change of the Vmax. Treatment of the acidotic animals with intraperitoneal 1,25 dihydroxycholecalciferol did not restore phosphate transport to control levels. These studies indicate that in weanling rats, metabolic acidosis selectively suppresses jejunal phosphate transport independent of circulating levels of 1,25 dihydroxycholecalciferol.
The development of metabolic acidosis during neonatal sepsis with group B streptococci (GBS) has been attributed to progressive tissue ischemia resulting from reduced oxygen delivery (QO2). Using an animal model of GBS disease, we attempted to test this hypothesis by comparing the development of metabolic acidosis in two groups of piglets with comparably diminished systemic QO2, one septic and one not. Eighteen anaesthetized piglets were instrumented to observe aortic pressure, cardiac output, arterial and mixed venous blood gases, oxygen content, and hemoglobin concentration. QO2, oxygen consumption, and oxygen extraction ratio were calculated. Six piglets (group 1) received continuous infusion of live GBS organisms; six piglets (group 2) received continuous infusion of phenylephrine (PE), beginning with 10-micrograms/kg/min and increasing as required to match the PE-induced reduction in QO2 to the fall observed in the group 1 (GBS) piglets at each 30-min interval. Group 3 piglets (n = 6) received 0.9% saline and served as controls. No differences in either cardiac output or QO2 were noted comparing GBS and PE piglets at any time interval from 0-180 minutes. At 120, 150, and 180 minutes, both QO2 and cardiac output were lower in GBS and PE piglets compared to controls. Despite equivalent reductions in cardiac output and QO2, only GBS piglets developed significant metabolic acidosis, while pH and base deficit for PE piglets did not differ from controls. Oxygen consumption did not differ significantly among the three experimental groups at any observation time. Oxygen extraction ratio did not differ comparing PE and GBS piglets at any observation time.(ABSTRACT TRUNCATED AT 250 WORDS)
Acidic media have been reported to inhibit the hydro-osmotic effect of vasopressin in toad bladders, probably through inhibition of the cyclic AMP system. However, the mechanism of inhibition of the cyclic AMP system is controversial. Therefore, that inhibitory mechanism was further investigated in rat kidneys. The antidiuretic response to vasopression was significantly inhibited in animals with metabolic acidosis. The inhibition of the antidiuretic response was associated with a smaller than normal increase of urinary excretion of cyclic AMP after the iv injection of vasopressin. In in vitro experiments, both the increase of cyclic AMP concentration in renal medullary slices and the activation of adenylate cyclase in medulla by vasopressin were significantly less in acidic than in control media. These findings suggest that medabolic acidosis inhibits the antidiuretic effect of vasopressin by inhibiting the vasopressin-dependent cyclic AMP system in the kidney. Acidic media also inhibited cyclic AMP-phosphodiesterase. These dual effects of acidosis on adenylate cyclase and cyclic AMP-phosphodiesterase may explain the conflicting findings observed in the experiments on toad bladders.
OBJECTIVE: To evaluate the role of chronic cerebral lactic acidosis in mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). METHODS: The authors studied 91 individuals from 34 families with MELAS and the A3243G point mutation and 15 individuals from two families with myoclonus epilepsy and ragged red fibers (MERRF) and the A8344G mutation. Subjects were divided into four groups. Paternal relatives were studied as controls (Group 1). The maternally related subjects were divided clinically into three groups: asymptomatic (no clinical evidence of neurologic disease) (Group 2), oligosymptomatic (neurologic symptoms but without the full clinical picture of MELAS or MERRF) (Group 3), and symptomatic (fulfilling MELAS or MERRF criteria) (Group 4). The authors performed a standardized neurologic examination, neuropsychological testing, MRS, and leukocyte DNA analysis in all subjects. RESULTS: The symptomatic and oligosymptomatic MELAS subjects had significantly higher ventricular lactate than the other groups. There was a significant correlation between degree of neuropsychological and neurologic impairment and cerebral lactic acidosis as estimated by ventricular MRS lactate levels. CONCLUSIONS: High levels of ventricular lactate, the brain spectroscopic signature of MELAS, are associated with more severe neurologic impairment.
UNLABELLED: In this study, we evaluated the action of two buffer solutions on acid-base equilibrium in cases of hyperchloremic acidosis. Twenty-four patients undergoing major gynecological intraabdominal surgery received 40 mL. kg(-1). h(-1) of 0.9% saline per protocol. During surgery, in every patient, hyperchloremic acidosis occurred. At a standard base excess of -7 mmol/L, the patients were randomly assigned to receive within 20 min either a mean of 130 +/- 26 mmol of sodium bicarbonate (BIC, 1 M; n = 12) or a mean of 128 +/- 18 mmol of tris-hydroxymethyl aminomethane (THAM, 3 M; n = 12). PaCO(2), pH, serum bicarbonate concentration, standard base excess, and serum concentrations of sodium, potassium, chloride, lactate, phosphate, total protein, and albumin were determined before and 0, 10, and 20 min after buffering. The apparent strong ion difference was calculated as: serum sodium plus serum potassium minus serum chloride minus serum lactate. The effective strong ion difference and the amount of weak plasma acid were calculated by using a computer program. Immediately after buffering, standard base excess increased by 9.8 mmol/L in the BIC group and by 7.2 mmol/L in the THAM group. In both groups, PaCO(2) and the amount of weak plasma acid remained constant. Mainly because of hypernatremia, the apparent and effective strong ion difference increased in the BIC group by 8.5 and 7.9 mEq/L, respectively. In the THAM group, the apparent strong ion difference remained constant; however, the effective strong ion difference increased by 6.4 mEq/L and the anion gap decreased by 5.8 mmol/L because of the occurrence of an unmeasured cation. In conclusion, in case of buffering with BIC or THAM, the changes in pH were accompanied by, and probably caused by, an increase in strong ion difference. IMPLICATIONS: By comparing two groups of patients with intraoperative hyperchloremic acidosis receiving equal doses of either sodium bicarbonate or tris-hydroxymethyl aminomethane, we assessed the action of both drugs on acid-base equilibrium. In case of "buffering," the changes in pH were accompanied by, and probably caused by, an increase in strong ion difference.