salicylates and Acidosis

Altered level of consciousness describes the reason for 3% of critical emergency department (ED) visits. Approximately 85% will be found to have a metabolic or systemic cause. Early laboratory studies such as a bedside glucose test, serum electrolytes, or a urine dipstick test often direct the ED provider toward endocrine or metabolic causes. This article examines common endocrine and metabolic causes of altered mentation in the ED via sections dedicated to endocrine-, electrolyte-, metabolic acidosis-, and metabolism-related causes.

Topics: Acidosis; Aged; Child; Consciousness Disorders; Cushing Syndrome; Diabetic Ketoacidosis; Ethylene Glycol; Female; Glucose Metabolism Disorders; Humans; Hyperammonemia; Inappropriate ADH Syndrome; Metabolic Diseases; Methanol; Pregnancy; Salicylates; Thyroid Diseases; Water-Electrolyte Imbalance

Intoxications present in many forms including: known drug overdose or toxic exposure, illicit drug use, suicide attempt, accidental exposure, and chemical or biological terrorism. A high index of suspicion and familiarity with toxidromes can lead to early diagnosis and intervention in critically ill, poisoned patients. Despite a paucity of evidence-based information on the management of intoxicated patients, a rational and systematic approach can be life saving.

Topics: Acidosis; Amphetamines; Carbon Monoxide Poisoning; Critical Illness; Hospitalization; Humans; Insecticides; Methemoglobinemia; Organophosphorus Compounds; Osmolar Concentration; Poisoning; Salicylates

Although topical salicylates are widely used, toxicity from this route is rare.. We present an unusual case of salicylism from a topical salicylate preparation in an 80-year-old woman. The patient was admitted to the dermatology service with a diagnosis of erythroderma and was treated with salicylate containing ointments. After six days of treatment the patient became confused and paranoid. A serum salicylate was 3.36 mmol/L (46 mg/dL). The patient was admitted to the intensive care unit were she was rehydrated and treated with bicarbonate and activated charcoal.. Her serum salicylate fell to 1.90 mmol/L (26 mg/dL) over a two day period and she regained a normal mental status.

Topics: Acidosis; Administration, Topical; Aged; Aged, 80 and over; Cognition Disorders; Confusion; Dermatitis, Exfoliative; Drug Monitoring; Female; Humans; Keratolytic Agents; Paranoid Disorders; Risk Factors; Salicylates; Salicylic Acid; Sleep Stages

Topics: Acidosis; Bicarbonates; Biguanides; Diabetes Mellitus; Epilepsy; Ethanol; Fructose; Heart Failure; Humans; Hypoglycemic Agents; Lactates; Leukocytosis; Methanol; Neoplasms; Physical Exertion; Salicylates; Shock

Metabolic acidosis produced by drugs and/or chemicals can be conveniently divided into those with an increase in the anion gap (anion gap = Na- (Cl + HCO3)) and those with a normal anion gap. The increase in the anion gap is due to the accumulation of unmeasured organic anions, such as lactate or acetoacetate and beta-hydroxybutyrate, as occurs in ketoacidosis and lactic acidosis, or the accumulation of toxic anions such as formate or glycolate, as occurs with the ingestion of methanol or ethylene glycol. Increased concentrations of lactic acid may also be present in the toxic forms of metabolic acidosis. The most common drugs and chemicals that induce the anion gap type of acidosis are biguanides, alcohols, polyhydric sugars, salicylates, cyanide and carbon monoxide. In normal anion gap acidosis the reduction in bicarbonate is balanced by a reciprocal increase in the chloride concentration so that the sum of the two remains unchanged. Normal anion gap acidosis is caused by carbonic anhydrase inhibitors, hydrochloride salts of amino acids, toluene, amphotericin, spironolactone and non-steroidal anti-inflammatory drugs. The mechanism by which these substances produce metabolic acidosis and the therapy are discussed.

Topics: Acidosis; Adenosine Triphosphate; Age Factors; Animals; Biguanides; Carbon Monoxide; Catecholamines; Cyanides; Ethylene Glycols; Fructose; Humans; Isoniazid; Methanol; NAD; Salicylates

The roles of changes in cellular redox, interorgan lactate flux and balance, and quantitative aspects of lactate metabolism in the pathogenesis of lactic acidosis are discussed. Altered metabolism of pyruvate is central to the development of lactic acidosis and hyperlactatemia. Lactic acidosis occurs as a result of a relative or absolute imbalance in lactate production and utilization. Lactate utilization for oxidative purposes and for the resynthesis of glucose is essential for the maintenance of acid-base balance. Because of its role in lactate homeostasis the liver may play a central role in acid-base balance. Impairment of hepatic utilization of lactate may produce lactic acidosis.

Topics: Acidosis; Animals; Diabetic Ketoacidosis; Dichloroacetic Acid; Ethanol; Homeostasis; Humans; Hypoglycemia; Kidney; Lactates; Liver; Liver Diseases; Neoplasms; Phenformin; Renal Dialysis; Salicylates; Seizures; Vasodilator Agents

Topics: Acidosis; Animals; Bicarbonates; Biotransformation; Blood; Brain Chemistry; Carbon Dioxide; Carbon Isotopes; Dogs; Emetics; Extracorporeal Circulation; Gastric Lavage; Humans; Hydrogen-Ion Concentration; Liver; Mice; Muscles; Poisoning; Rats; Renal Dialysis; Salicylates

Topics: Acidosis; Anti-Bacterial Agents; Bilirubin; Blood Transfusion; Erythroblastosis, Fetal; Female; Gestational Age; Humans; Hyperbilirubinemia; Hypoproteinemia; Hypoxia; Infant, Newborn; Infant, Premature, Diseases; Infections; Infusions, Parenteral; Jaundice, Neonatal; Kernicterus; Liver; Phototherapy; Pre-Eclampsia; Pregnancy; Salicylates; Serum Albumin; Steroids; Sulfisoxazole

Topics: Acetaminophen; Acid-Base Equilibrium; Acidosis; Acute Kidney Injury; Alkalosis, Respiratory; Aspirin; Calcium; Coma; Dehydration; Fever; Gastric Lavage; Hemorrhage; Humans; Hydrogen-Ion Concentration; Infusions, Parenteral; Poisoning; Salicylamides; Salicylates; Seizures; Tetany; Vomiting

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic antinociception.

Topics: Acidosis; Administration, Topical; Adult; Aspirin; Cross-Over Studies; Double-Blind Method; Female; Humans; Indomethacin; Injections, Intradermal; Isotonic Solutions; Male; Middle Aged; Palliative Care; Pressure; Salicylates; Salicylic Acid; Skin Diseases

Severe salicylate intoxication usually presents with a high anion gap metabolic acidosis. We describe a patient with severe salicylate intoxication who presented with a surprisingly normal anion gap metabolic acidosis. Initial salicylate level was 594 mg/L (therapeutic range 50-300 mg/L). In this case, the anion gap was normal due to a falsely elevated chloride concentration measured using a direct ion-selective electrode (ISE; ABL90-flex). Since earlier case reports have shown that salicylate ions can interfere with chloride measurement using different ISEs, available samples were reanalysed using an indirect ISE (Roche Cobas 8000), in which salicylate levels up to 1000 mg/L were found to cause no significant interference. With this method, chloride concentration was found to be 115 instead of 122 mmol/L, leading to the expected elevated anion gap. We performed a spike experiment to investigate the impact of different salicylate levels and bicarbonate concentrations on the measured chloride concentration for both methods. This experiment showed that the difference between chloride concentrations was mainly explained by interference with bicarbonate. It is important for clinicians to be aware of this possible interference, since a high anion gap metabolic acidosis can be a clue to suspect salicylate poisoning and early recognition and appropriate treatment is important. The patient was successfully treated with haemodialysis and no rebound toxicity was observed.

Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Chlorides; Humans; Salicylates

Pseudohyperchloremia results in a very low or negative anion gap. Historically, the most common cause of this artifact was bromide poisoning. Bromide salts have been removed from most medications and bromism has become very uncommon. More recently, the introduction of chloride ion selective sensing electrodes (Cl-ISE) has generated a new cause of pseudohyperchloremia-salicylate poisoning. We describe 5 such patients and quantitate the error generated by this measurement artifact.. The magnitude of artifactual hyperchloremia generated by high salicylate levels was quantified in 5 patients by measuring chloride concentration with several Cl-ISEs from different manufacturers and with Cl-ISEs of different "ages," and comparing these results to measurements with a chloridometer (coulometric titration), which is free of the salicylate artifact.. Cl-ISEs from different manufacturers generated a wide range of artifactual chloride concentration elevation. Furthermore, the same Cl-ISE generated increasingly severe pseudohyperchloremia as it was repeatedly reused over time and "aged.". Salicylate interferes with measurement of the blood chloride concentration when a Cl-ISE is used. The severity of this artifact is related to the salicylate level, the specific Cl-ISE, and the "age" of the electrode. Toxic blood salicylate levels can generate marked pseudohyperchloremia, and consequently, an artifactual very small or negative anion gap. The large anion gap metabolic acidosis typical of salicylate poisoning is masked by this artifact. Salicylate has become the most common cause of pseudohyperchloremia, and physicians should immediately consider salicylate poisoning whenever the combination of hyperchloremia and a very small or negative anion gap is reported by the laboratory.

Topics: Acid-Base Equilibrium; Acid-Base Imbalance; Acidosis; Artifacts; Aspirin; Chlorides; Equipment Failure Analysis; Female; Humans; Ion-Selective Electrodes; Male; Middle Aged; Patient Care; Salicylates; Suicide, Attempted

Acute metabolic acidosis is rarely associated with a reduced or negative anion gap (AG), but several case reports have described such an abnormality occurring in the setting of acute salicylate intoxication. The underlying cause of this phenomenon is unclear.. In this retrospective cohort study, we reviewed our institutional database to identify all patients admitted for salicylate intoxication at Mayo Clinic (Rochester, MN, USA) from January 2010 through December 2012. Serum chloride was measured with the Cobas INTEGRA 400 plus electrode (expedited laboratory test) or Cobas 6000 (routine laboratory test). We compared blood chloride levels measured by the 2 devices in the presence of positive blood salicylate level.. Twelve adult patients with salicylate levels >20 mg/dL had markedly elevated chloride concentrations. The median (interquartile range) chloride level at admission was 120 (107-145) mmol/L on their initial laboratory studies, resulting in reduced or even negative AGs. None of the patients had bromide toxicity, nor did they have any other identifiable cause of hyperchloremia or decreased AG. Further testing of the same blood samples with an alternative measurement system (Roche Cobas 6000) yielded normal chloride values, indicating that falsely elevated chloride values with the initial testing led to the diminished or negative AG values.. Circulating levels of salicylate can interfere with chloride measured by using routine techniques, resulting in spurious hyperchloremia outcomes and erroneous AG values. In patients with acute metabolic acidosis and abnormally reduced or negative AG, salicylate interference with chloride measurement should be suspected.

Topics: Acidosis; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Bromides; Chlorides; Cohort Studies; Databases, Factual; False Positive Reactions; Female; Humans; Male; Middle Aged; Retrospective Studies; Salicylates; Water-Electrolyte Imbalance; Young Adult

For patients who have had a recent neurosurgical procedure, a visit to the emergency department for encephalopathy may automatically prompt a neurosurgical consult. We present a case of a patient with a history of Chiari malformation decompressed 6 months prior who presented with a 2-week history of slowly progressive altered mental status, headache and imbalance-symptoms consistent with her initial Chiari symptoms, so neurosurgery was consulted. Imaging showed no acute abnormality, but laboratory results revealed metabolic acidosis with high salicylate levels. When reporting medication use, this patient initially left out that she had been taking Goody's powder (845 mg aspirin) for headaches, and long-term use led to metabolic encephalopathy. Despite a recent history of surgery, it is important to keep the differential diagnosis broad especially when there are signs of metabolic derangement.

Topics: Acidosis; Aftercare; Arnold-Chiari Malformation; Brain; Brain Diseases; Diagnosis, Differential; Female; Headache; Humans; Infusions, Intravenous; Mental Disorders; Middle Aged; Neurosurgical Procedures; Salicylates; Sodium Bicarbonate; Tomography, X-Ray Computed; Treatment Outcome

Salicylate poisoning remains a significant public health threat with more than 20,000 exposures reported annually in the United States.. We aimed to establish early predictors of severe in-hospital outcomes in Emergency Department patients presenting with acute salicylate poisoning.. This was a secondary data analysis of adult salicylate overdoses from a prospective cohort study of acute drug overdoses at two urban university teaching hospitals from 2009 to 2013. Patients were included based on confirmed salicylate ingestion and enrolled consecutively. Demographics, clinical parameters, treatment and disposition were collected from the medical record. Severe outcome was defined as a composite occurrence of acidemia (pH <7.3 or bicarbonate <16 mEq/L), hemodialysis, and/or death.. Out of 1997 overdoses screened, 48 patients met inclusion/exclusion criteria. Patient characteristics were 43.8% male, median age 32 (range 18-87), mean initial salicylate concentration 28.1 mg/dL (SD 26.6), and 20.8% classified as severe outcome. Univariate analysis indicated that age, respiratory rate, lactate, coma, and the presence of co-ingestions were significantly associated with severe outcome, while initial salicylate concentration alone had no association. However, when adjusted for salicylate concentration, only age (OR 1.13; 95% CI 1.02-1.26) and respiratory rate (OR 1.29; 95% CI 1.02-1.63) were independent predictors. Additionally, lactate showed excellent test characteristics to predict severe outcome, with an optimal cutpoint of 2.25 mmol/L (78% sensitivity, 67% specificity).. In adult Emergency Department patients with acute salicylate poisoning, independent predictors of severe outcome were older age and increased respiratory rate, as well as initial serum lactate, while initial salicylate concentration alone was not predictive.

Topics: Acidosis; Acute Disease; Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Cohort Studies; Drug Overdose; Emergency Service, Hospital; Female; Hospitals, University; Humans; Male; Middle Aged; Prospective Studies; Renal Dialysis; Risk Factors; Salicylates; Sensitivity and Specificity; Severity of Illness Index; Young Adult

Topics: Acid-Base Equilibrium; Acidosis; Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Biomarkers; Female; Humans; Middle Aged; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Acute Kidney Injury; Humans; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Adolescent; Drug Overdose; Female; Humans; Salicylates

Topics: Abdomen; Acidosis; Diagnosis, Differential; Humans; Infant; Lethargy; Male; Poisoning; Renal Dialysis; Respiratory Insufficiency; Salicylates; Tachypnea

Salicylate poisoning classically results in an increased anion gap metabolic acidosis. We discuss a case of normal anion gap metabolic acidosis despite elevated serum salicylate concentration. This diagnostic dilemma stemmed from aberrant reading of salicylate ions by analyzer electrodes as chloride ions leading to falsely negative anion gap. On review, this phenomenon is found to be possible with a number of commonly used analyzers. In emergency department settings, high level of clinical suspicion for salicylate poisoning should be maintained, and metabolic acidosis with normal anion gap should not be used to rule out salicylate overdose. This can prevent significant avoidable morbidity and mortality.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Chlorides; Drug Overdose; Emergency Service, Hospital; Humans; Male; Salicylates

Aspirin and its main metabolite salicylate are widely used to relieve pain, treat inflammatory diseases, and prevent ischemic stroke. Multiple pathways are responsible for the therapeutic actions exerted by these drugs. One of the pathways is targeting neuronal receptors/ion channels in the central nervous system. Correspondingly, increasing evidence has implicated acid-sensing ion channels (ASICs) in the processes of the diseases that are medicated by aspirin and salicylate. We therefore employed whole-cell patch-clamp recordings to examine the effects of salicylate as well as aspirin on ASICs in cultured cortical neurons of the rat. We recorded rapid and reversible inhibition of ASIC current by millimolar concentrations of aspirin and salicylate and found that salicylate reduced acidosis-induced membrane depolarization. These data suggest that ASICs in the cortex are molecular targets of high doses of aspirin and salicylate. In addition, the results from lactate dehydrogenase release measurement showed that high doses of aspirin and salicylate protected the cortical neuron from acidosis-induced neuronal injury. These findings may contribute to a better understanding of the therapeutic mechanisms of aspirin and salicylate actions in the brain and provide new evidence on aspirin and salicylate used as neuroprotective agents in the treatment of ischemic stroke.

Topics: Acid Sensing Ion Channels; Acidosis; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Cell Death; Cells, Cultured; Cerebral Cortex; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Embryo, Mammalian; Nerve Tissue Proteins; Neural Inhibition; Neurons; Patch-Clamp Techniques; Propidium; Rats; Rats, Sprague-Dawley; Salicylates; Sodium Channel Blockers; Sodium Channels; Tetrodotoxin

Topics: Acidosis; Aged; Confusion; Consciousness Disorders; Critical Care; Diagnostic Errors; Drug Overdose; Fatal Outcome; France; Humans; Salicylates; Schizophrenia

Mitochondrial acetoacetyl-CoA thiolase deficiency (or beta-ketothiolase deficiency) is a rare metabolic disorder characterized by acute episodes of severe acidosis and ketosis. A case is presented of an 18-month-old boy who presented with vomiting and diarrhoea and was found to be markedly acidotic. When the acidosis persisted despite saline fluid boluses and bicarbonate correction, further investigations were undertaken. Routine biochemical investigation revealed detectable salicylate concentrations despite the parents denying its administration, which initially caused some diagnostic confusion. The results of urine organic acid analysis, however, confirmed that the diagnosis of mitochondrial acetoacetyl-CoA thiolase deficiency. The high concentrations of acetoacetate present in the patient's sample resulted in a false-positive reaction in the Trinder assay for salicylate.

Topics: Acetoacetates; Acetyl-CoA C-Acetyltransferase; Acidosis; Acids; Amino Acid Metabolism, Inborn Errors; Chemistry, Clinical; False Positive Reactions; Humans; Infant; Ketosis; Male; Mitochondria; Salicylates; Time Factors

Despite little empiric evidence, mechanical ventilation (MV) in the setting of salicylate poisoning is considered by many to be harmful. When salicylate-poisoned patients are ventilated at conventional settings, the respiratory alkalosis is abolished, more salicylate is able to pass into the central nervous system (CNS), and neurotoxicity worsens. The objective of this study was to identify a relationship between MV, acidosis, and outcome in salicylate-poisoned patients.. The authors electronically searched a poison control center (PCC) database (2001-2007) for patients with salicylate poisoning, defined as a serum concentration > 50 mg/dL, who had MV listed as a therapy. For the 7-year study period, a total of 3,144 salicylate-poisoning cases were identified. Eleven patients met the inclusion criteria of having both salicylate concentrations > 50 mg/dL and required MV; only 7 of them had post-MV data available.. In all seven patients with post-MV blood gas data, the post-MV pH was < 7.4. In five of six patients with recorded PCO2, the post-MV PCO2 was > 50 mm Hg. Two of the seven patients in the study group died following intubation (two patients died within 3 hours [serum salicylate concentrations, 85 and 79 mg/dL, respectively]). Another patient sustained severe neurologic injury (serum salicylate concentration, 84 mg/dL). The other four patients were ultimately discharged home. In the three patients with the worst clinical outcome, deterioration was reported within hours of intubation.. Inadequate MV of patients with salicylate poisoning is associated with respiratory acidosis, acidemia, and clinical deterioration in this series of cases. This supports warnings about the danger of improper MV in patients with salicylate poisoning. A prospective study should be performed.

Topics: Acidosis; Humans; New York; Poisoning; Respiration, Artificial; Retrospective Studies; Salicylates; Treatment Outcome

Metabolic acidosis is associated with most severe malaria deaths in African children, and most deaths occur before maximum antimalarial action is achieved. Thus, specific acidosis treatment may reduce mortality. However, the underlying mechanisms remain poorly understood and no specific interventions have been developed. A detailed characterisation of this acidosis is critical in treatment development. We used the traditional and Stewart's approach to characterise acidosis in consecutive paediatric admissions for malaria and other acute non-surgical conditions to Kilifi District Hospital in Kenya. The overall acidosis prevalence was 21%. Gastroenteritis had the highest prevalence (61%). Both the mean albumin-corrected anion gap and the strong ion gap were high (>13 mmol/l and >0 mmol/l, respectively) in malaria, gastroenteritis, lower respiratory tract infection and malnutrition. Presence of salicylate in plasma was not associated with acidosis but was associated with signs of severe illness (odds ratio 2.11, 95% CI 1.1-4.2). In malaria, mean (95% CI) strong ion gap was 15 (14-7) mmol/l, and lactate, creatinine and inorganic phosphorous explained only approximately 40% of the variability in base excess (adjusted R2 = 0.397). Acidosis may be more common than previously recognised amongst paediatric admissions in Africa and is characterised by the presence of currently unidentified strong anions. In malaria, lactate and ketones, but not salicylate, are associated with acidosis. However, unidentified anions may be more important.

Topics: 3-Hydroxybutyric Acid; Acidosis; Acute Disease; Biomarkers; Child, Preschool; Creatinine; Female; Gastroenteritis; Hospitalization; Humans; Infant; Kenya; Ketones; Lactates; Lung Diseases; Malaria; Male; Malnutrition; Regression Analysis; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Adenosine Triphosphatases; Analgesics; Cytochromes; Ethylene Glycol; Humans; Male; Poisoning; Propylene Glycol; Salicylates

Topics: Acidosis; Adult; Alkalosis, Respiratory; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Charcoal; Child; Drug Overdose; Humans; Salicylates; Sorption Detoxification

BACKGROUND Salicylates continue to be marketed and to be used in developing countries as over-the-counter (OTC) antipyretics in children, whereas in developed countries they are no longer used in children because of safety concerns. The presenting signs of salicylate poisoning, especially chronic (repeated administration of therapeutic or excessive doses for longer than 12 h), can include metabolic acidosis, hypoglycaemia, lethargy, and coma and fits. These signs are also common in severe malaria in African children. Admission of two probable cases of chronic salicylate poisoning prompted us to look for other cases among children presenting to our hospital in Kenya, apparently with severe malaria. METHODS All children admitted to Kilifi District Hospital between July and September, 1994, who had a positive blood film for Plasmodium falciparum, and one or more of coma, prostration, or respiratory distress were eligible. As well as routine tests for malaria and routine biochemistry, salicylate concentrations were measured. Management of children (aged 6 months to 10 years) in the community was assessed by a cross-sectional survey of 463 households and by interviews with mothers 2 days after they had bought OTC drugs for a child with fever. FINDINGS Data were available for 143 of 154 children with initial primary diagnoses of severe malaria. 129 (90 percent) had detectable (>l mg/dL) salicylate. Six of these had salicylate concentrations of 20 mg/dL or higher. All six had neurological impairment and metabolic acidosis and four were, or became, hypoglycaemic. OTC drugs were the first-line treatment in 188 (74 percent) of 254 fever episodes during the 2 weeks before the cross-sectional survey. Of 250 mothers who bought drugs for a febrile child, 236 (94 percent) bought a preparation containing salicylates and 50 (21 percent) gave a dose higher than the manufacturer's recommended maximum. INTERPRETATION These cases suggest that in some children salicylate poisoning may cause or contribute to the development of metabolic acidosis and hypoglycaemia, complications of severe malaria associated with high mortality.

Topics: Acidosis; Child; Child, Preschool; Cross-Sectional Studies; Female; Humans; Infant; Kenya; Malaria, Falciparum; Male; Salicylates

Topics: Acidosis; Adult; Alkalosis, Respiratory; Bicarbonates; Charcoal; Female; Humans; Poisoning; Salicylates; Sodium; Sodium Bicarbonate; Suicide, Attempted

1. The basis for the existence of a lower concentration of salicylate in the foetal than in the maternal blood was investigated in rats on day 20 of gestation. 2. Bolus injections of sodium salicylate were made into the mother and of [14C]-salicylic acid into its foetuses and serial maternal and foetal blood samples were collected. When derived on the basis of serum salicylic acid uncorrected for differences in ionization in the maternal and foetal blood, the placental clearance was 2.2 fold greater from the foetal to maternal side than that from the maternal to foetal side. 3. The greater foetal placental clearance relative to the maternal placental clearance was not due to any active placental transfer, since there was no evidence of saturation of this process and it was not affected by pretreatment with probenecid. Moreover, salicylic acid was not concentrated by placental slices in vitro and its placental uptake was not affected by dinitrophenol or by cooling. 4. Maternal blood pH was 0.19 units higher than the foetal blood pH. Administration of ammonium chloride or of sodium bicarbonate into the mother increased the foetal to maternal ratio of salicylic acid from 0.6 to approximately 1. 5. It is concluded that a foetal to maternal serum salicylate concentration-ratio of less than 1 simply reflects lower ionization in the foetus than in the mother, because foetal blood pH is lower than the maternal blood pH.

Topics: Acidosis; Alkalosis; Ammonium Chloride; Animals; Bicarbonates; Blood Gas Analysis; Female; Hydrogen-Ion Concentration; In Vitro Techniques; Maternal-Fetal Exchange; Placenta; Pregnancy; Probenecid; Rats; Rats, Inbred Strains; Salicylates; Sodium; Sodium Bicarbonate

Understanding of the pharmacologic principles and the pathogenesis of salicylate toxicity provides a basis for the optimization of clinical management. The role of salicylate as a scientifically proven cause of Reye's syndrome remains controversial despite epidemiologic data. The management guidelines discussed illustrate treatment details based on the pathophysiology of salicylate toxicity.

Topics: Absorption; Acidosis; Blood-Brain Barrier; Brain; Charcoal; Child, Preschool; Fluid Therapy; Gastric Lavage; Glucose; Humans; Hydrogen-Ion Concentration; Hypoglycemia; Infant; Kinetics; Nausea; Respiratory Center; Reye Syndrome; Salicylates

Two young patients with unimpaired renal and hepatic function were found to have developed metabolic acidosis after treatment for glaucoma and joint pain with a combination of salicylates and carbonic anhydrase inhibitors in normal doses. Carbonic anhydrase inhibitors appear to interact with salicylates to produce serious metabolic acidosis in patients without the predisposing factors generally considered to constitute risks. It is recommended that treatment combining salicylates and carbonic anhydrase inhibitors is either kept to a minimum or avoided.

Topics: Acetazolamide; Acidosis; Adult; Arthritis; Aspirin; Carbonic Anhydrase Inhibitors; Child; Dichlorphenamide; Drug Interactions; Drug Therapy, Combination; Female; Glaucoma; Humans; Male; Salicylates

Mucormycosis is an often-fatal opportunistic fungal infection caused by members of the class Zygomycetes (Phycomycetes), order Mucorales. Most cases are diagnosed by histologic examination, through the identification of mucormycotic hyphae in infected tissues. Chronic debilitating conditions accompanied by acidosis such as diabetes mellitus, as well as leukemia, lymphoma, and immunodeficient states, predispose to the development of this type of opportunistic infection. This report describes a hitherto undescribed finding, the presence of structures consistent with sporangia in tissue sections, in a case of pulmonary mucormycosis occurring in a nondiabetic patient with metabolic acidosis secondary to chronic salicylate poisoning.

Topics: Acidosis; Aged; Humans; Lung Diseases, Fungal; Male; Mucormycosis; Rhizopus; Salicylates; Spores, Fungal

Topics: Acidosis; Adult; Central Nervous System; Child; Dialysis; Gastric Lavage; Humans; Potassium; Salicylates

Noncardiogenic pulmonary edema occurs in 35% of salicylate-intoxicated patients who are over 30 years old. Cigarette smoking, chronic salicylate ingestion, a component of metabolic acidosis, and the presence of neurological symptoms on admission are strong risk factors for the subsequent development of pulmonary edema in the appropriate age group. In the absence of these risk factors, salicylate-induced pulmonary edema is rare. The etiology is multifactorial, but it centers around altered vascular permeability in the lungs.

Topics: Acidosis; Acidosis, Respiratory; Adolescent; Adult; Aged; Capillary Permeability; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Lung; Male; Middle Aged; Pulmonary Edema; Radiography; Risk; Salicylates; Smoking

Improvements in nuclear magnetic resonance (NMR) technology are generating an expanding variety of medical applications. In this investigation I have used high-field proton NMR to identify and quantity endogenous and ingested substances in human serum. After addition of a small amount of 2H2O and a reference compound to a 0.4-mL specimen, spectra were recorded for 3 min in Fourier-transform mode, with use of presaturation to suppress the extremely intense H2O peak. Compounds detected at clinically significant concentrations include glucose, alcohols, acetone, organic acids, and salicylate. Less than 1 mmol/L of some of these substances could be detected. For serum containing 20--500 mg of added methanol per liter, peak area was a linear function of concentration (r = 0.998). High-field proton NMR, despite the drawback of expensive, sophisticated instrumentation, offers some unique advantages for clinical chemistry: it permits rapid, specific, nondestructive measurement of several compounds simultaneously, including some that may be inconvenient to measure by conventional means.

Topics: Acidosis; Adult; Aged; Blood Chemical Analysis; Blood Glucose; Diabetic Ketoacidosis; Ethanol; Humans; Lactates; Magnetic Resonance Spectroscopy; Male; Methanol; Phenobarbital; Salicylates

To evaluate the relative severity of acute vs chronic salicylate poisoning in children, 112 cases (65 acute and 47 chronic) of salicylate poisoning (salicylate concentration greater than or equal to 20 mg/100 ml) admitted to The Children's Hospital Medical Center in Boston and Primary Children's Medical Center in Salt Lake City between the years 1967 and 1978 were analyzed. Hyperventilation (P less than .01), dehydration (P less than .001), and severe central nervous system manifestations (P less than .001) occurred more frequently in the chronic group and remained more frequent (P less than .01) when patients having disease states capable of producing these signs and symptoms were removed from statistical analysis. At three separate salicylate concentration ranges (20 to 39, 40 to 59, and greater than or equal to 60 mg/100 ml) hyperventilation, dehydration, and severe CNS manifestations tended to occur with greater frequency in the chronic group. When severity of salicylate poisoning was categorized based on a combination of signs and symptoms, mild cases occurred more frequently in the chronic group. Finally, systemic acidosis (pH less than 7.32) was found more frequently in the chronic group (P less than .01), more frequently in patients with severe manifestations than in those with mild manifestations, and in patients with dehydration (P less than .01) and severe CNS manifestations (P less than .05). Based on the variables evaluated, chronic salicylism produces a greater morbidity than does acute salicylate poisoning in the pediatric patient.

Topics: Acidosis; Acute Disease; Adolescent; Central Nervous System Diseases; Child; Child, Preschool; Chronic Disease; Dehydration; Female; Humans; Hyperventilation; Infant; Male; Nausea; Salicylates; Vomiting

Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Carbon Dioxide; Humans; Hypokalemia; Potassium; Salicylates

All patients in stupor or coma should undergo blood chemistry studies, including blood gases. The anion gap and serum osmolality must be calculated in all patients. An indwelling catheter to monitor urine content and volume is essential. Electrocardiogram monitoring is indicated in all significant metabolic acidosis, especially for evaluation of intracellular potassium effect and arrhythmias. Repeated arterial monitoring of blood gases and electrolytes is essential with the use of flow sheets. Sodium lactate and Ringer's solution should never be given in an emergency care area. Large doses of insulin (100+ units intravenously) are not necessary or indicated in diabetic ketoacidosis and may be contraindicated and dangerous especially in HHNKC. Intravenous or intramuscular regular insulin after urine tests for glucose and ketones alone should not be given. Urine dilution of serum ketones is useless, and serum dilution may be grossly misleading and contraindicated: arterial studies are much more reliable.

Topics: Acidosis; Blood Glucose; Diabetic Ketoacidosis; Diagnosis, Differential; Electrolytes; Emergencies; Ethylene Glycols; Humans; Hypoglycemia; Lactates; Metabolic Diseases; Methanol; Salicylates; Uremia

This is a report of a 16-day-old, breast-fed infant who presented with metabolic acidosis and no history of drug ingestion. Salicylate intoxication was demonstrated as the probable cause of the acidosis.

Topics: Acidosis; Breast Feeding; Female; Humans; Infant, Newborn; Infant, Newborn, Diseases; Milk, Human; Salicylates

Topics: Acidosis; Aged; Humans; Male; Ointments; Salicylates; Skin Absorption

A female child presented at one year of age with a febrile illness and loose stools, then developed severe ketoacidosis with vomiting; an apparent salicylate level of 11 mg/dl was measured. A sibling had died in similar circumstances nine years earlier. Investigation revealed that the child did not have salicylate intoxication, and that high levels of acetoacetate in blood and urine were giving readings indicative of the presence of salicylate on routine testing. Gas-liquid chromatographic analysis combined with mass spectrometry on urine samples revealed the presence of 2-methyl-acetoacetate, 2-methyl-3-hydroxybutyrate, and tiglyl glycine in appreciable amounts, indicating a defect in isoleucine catabolism located at the beta-ketothiolase step. The oxidation of 14C-isoleucine to CO2 in cultured fibroblasts confirmed that this pathway was defective. We present evidence that beta-ketothiolase deficiency is not simply a defect of isoleucine degradation; the deficient enzyme is the K+ dependent short-chain mitochondrial thiolase, which also plays a major catalytic role in ketone body and fatty acid oxidation.

Topics: Acetoacetates; Acetyl-CoA C-Acetyltransferase; Acetyltransferases; Acidosis; Adolescent; Carbon Dioxide; Child, Preschool; Chromatography, Gas; Deficiency Diseases; Diagnosis, Differential; Fatty Acids; Female; Humans; Isoleucine; Ketone Bodies; Ketosis; Mass Spectrometry; Oxidation-Reduction; Salicylates

A 78-year-old nondiabetic woman was admitted to the hospital with salicylate-induced hypoglycemia. Ketosis was present with a moderate metabolic acidosis and primary respiratory alkalosis. The patient's mental status improved immediately following intravenous administration of glucose. The case illustrates salicylate's hypoglycemic activity, and that the metabolic acidosis may have exacerbated symptoms of cerebral glucopenia.

Topics: Acidosis; Aged; Alkalosis, Respiratory; Aspirin; Female; Glucose; Humans; Hypoglycemia; Infusions, Parenteral; Ketosis; Salicylates

Topics: Acidosis; Age Factors; Alkalosis, Respiratory; Blood-Brain Barrier; Capillary Permeability; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Meninges; Metabolic Clearance Rate; Prognosis; Salicylates; Severity of Illness Index; Tissue Distribution

Out of 14 cases of poisoning assumed to be due to dextropropoxyphene-containing drugs, propoxyphene and its main metabolite norpropoxyphene could be demonstrated in 11. The concentrations of the drugs were determined shortly after admission and then after 2, 4, 6 and 10 hours (in four cases also after 16 hours). The highest plasma concentration of propoxyphene, 0.74 mug/ml, was found in one case of fatal poisoning. Another patient with a plasma concentration of 0.51 mug/ml showed signs of severe respiratory depression but survived after respirator therapy. In the patients with lower plasma concentrations the poisoning had a benign course. In most cases the plasma concentration of norpropoxyphene exceeded that of propoxyphene even in the first blood sample.

Topics: Acidosis; Acute Disease; Adolescent; Adult; Arrhythmia, Sinus; Aspirin; Barbiturates; Dextropropoxyphene; Drug Combinations; Ethanol; Female; Humans; Male; Middle Aged; Respiration Disorders; Salicylates; Time Factors; Ventricular Fibrillation

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Alkalosis; Alkalosis, Respiratory; Animals; Bicarbonates; Brain; Calcium; Cerebrospinal Fluid; Humans; Hydrocephalus; Hydrogen-Ion Concentration; Hyperventilation; Intracranial Pressure; Magnesium; Potassium; Radioisotopes; Salicylates

Topics: Acidosis; Alkalosis; Alkalosis, Respiratory; Animals; Aspirin; Child; Child, Preschool; Dehydration; Fever; Humans; Hyperglycemia; Infant; Papio; Poisoning; Salicylates

Topics: Acidosis; Aged; Blood Urea Nitrogen; Bradycardia; Catheterization; Female; Heart Failure; Hepatic Encephalopathy; Humans; Hyperglycemia; Kidney Failure, Chronic; Male; Methanol; Middle Aged; Peritoneal Dialysis; Pyelonephritis; Salicylates

Topics: Acidosis; Animals; Blood; Child; Dogs; Humans; Hydrogen-Ion Concentration; Kinetics; Pediatrics; Peritoneal Dialysis; Salicylates

Topics: Acidosis; Adult; Female; Humans; Malignant Hyperthermia; Phenelzine; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Alkalosis, Respiratory; Biotransformation; Blood Gas Analysis; Humans; Infant; Infant, Newborn; Poisoning; Protein Binding; Salicylates; Serum Albumin

Topics: Acidosis; Animals; Bilirubin; Binding Sites; Cattle; Chemical Phenomena; Chemistry; Heme; Humans; Hydrogen-Ion Concentration; Kernicterus; Protein Binding; Salicylates; Serum Albumin; Serum Albumin, Bovine; Solubility; Sulfisoxazole; Sulfonamides

Topics: Acid-Base Equilibrium; Acidosis; Cardiovascular Diseases; Coma; Fever; Gastric Lavage; Gastrointestinal Diseases; Humans; Hydrogen-Ion Concentration; Hyperventilation; Neurologic Manifestations; Oxygen Consumption; Peritoneal Dialysis; Renal Dialysis; Salicylates; Water-Electrolyte Balance

Topics: Acidosis; Adult; Alkalosis, Respiratory; Anuria; Bicarbonates; Child; Gastric Lavage; Humans; Infusions, Parenteral; Poisoning; Potassium; Salicylates; Water-Electrolyte Balance

Topics: Acidosis; Aged; Alcoholic Intoxication; Alkalosis; Alkalosis, Respiratory; Arrhythmias, Cardiac; Coma; Diabetic Ketoacidosis; Diagnosis, Differential; Encephalitis, Arbovirus; Humans; Male; Myocardial Infarction; Poisoning; Salicylates; Stomach Neoplasms; Sweating

Topics: Acidosis; Acute Kidney Injury; Adrenal Insufficiency; Alkalosis; Alkalosis, Respiratory; Carbohydrates; Dehydration; Diabetic Ketoacidosis; Electrolytes; Heat Exhaustion; Humans; Hyperkalemia; Hypernatremia; Hypokalemia; Hyponatremia; Nutritional Requirements; Parenteral Nutrition; Potassium Deficiency; Proteins; Pyloric Stenosis; Salicylates; Shock; Sodium; Vitamins; Water Intoxication

Topics: Acidosis; Adult; Child; Diuresis; Gastric Lavage; Humans; Renal Dialysis; Salicylates

Topics: Acetazolamide; Acidosis; Adult; Bicarbonates; Child; Humans; Poisoning; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Acidosis, Respiratory; Alkalosis; Alkalosis, Respiratory; Arteries; Asthma; Carbon Dioxide; Education, Medical; Female; Heart Arrest; Humans; Hydrogen-Ion Concentration; Infant; Keto Acids; Kidney Failure, Chronic; Male; Mathematics; Middle Aged; Pulmonary Edema; Respiratory Insufficiency; Salicylates; Teaching

Topics: Acidosis; Acute Disease; Aspirin; Humans; Poisoning; Prognosis; Salicylates

Topics: Acidosis; Animals; Cardiac Output; Cardiomyopathies; Dogs; Heart; Hyperkalemia; Myocardium; Salicylates

Topics: Acid-Base Equilibrium; Acidosis; Bicarbonates; Dermatitis, Contact; Erythema; Humans; Infant; Male; Ointments; Salicylates; Scalp Dermatoses; Skin Absorption; Water-Electrolyte Balance

Topics: Acid-Base Equilibrium; Acidosis; Adult; Alkalies; Animals; Bicarbonates; Child; Diuresis; Dogs; Humans; Renal Dialysis; Salicylates

Topics: Acidosis; Aged; Female; Humans; Salicylates

A review of the arterial acid-base status on admission to hospital of 62 adults with severe salicylate poisoning showed that arterial pH was normal or high in most patients, but low in 8. The mean plasma salicylate concentrations of the acidaemic and nonacidaemic patients were similar and the difference in arterial pH was associated with a marked fall in standard bicarbonate in the former group. No significant difference of Pco(2) between the two groups was found, and hence no simple relationship exists between hypocapnia and the development of acidaemia in salicylate poisoning. Acidaemia is shown to be associated with impaired consciousness and to carry a grave prognosis.

Topics: Acidosis; Adolescent; Adult; Aged; Bicarbonates; Carbon Dioxide; Child; Female; Humans; Hydrogen-Ion Concentration; Male; Middle Aged; Prognosis; Salicylates; Unconsciousness

Topics: Acidosis; Alkalosis; Aniline Compounds; Animals; Blood Proteins; Cattle; Chemical Phenomena; Chemistry; Chlorpromazine; Hexobarbital; Hydrogen-Ion Concentration; Methohexital; Nitrofurantoin; Pentobarbital; Phenylbutazone; Protein Binding; Quinine; Salicylamides; Salicylates; Thiopental

Four patients who had ingested large amounts of phenacetin-salicylate medications were studied during a 12-month period. Renal failure had progressed slowly over a number of years. All patients took the drug because of psychogenic headache. Considerable skill was required to elicit the history of drug habituation. The major features of the nephropathy were multiple episodes of metabolic acidosis, minimal proteinuria, pyuria but no bacteriuria, and polyuria and polydipsia early in the course of drug ingestion. Papillary necrosis was not a prominent clinical feature of this series. Discontinuation of drug ingestion by one patient was associated with recovery of a considerable degree of renal function. Preliminary experimental evidence obtained in the dog suggests that salicylate impaired the efficiency of the counter-current multiplier by decreasing sodium transport in the ascending limb of Henle, and decreased the permeability to water of the distal convoluted and collecting tubule; phenacetin had no such effect.

Topics: Acidosis; Animals; Aspirin; Bacteriuria; Biological Transport; Caffeine; Codeine; Dogs; Drug Therapy; Headache; Humans; Kidney Diseases; Kidney Papillary Necrosis; Kidney Tubules; Metabolism; Neoplasm Recurrence, Local; Neoplasms; Phenacetin; Polyuria; Proteinuria; Pyuria; Salicylates; Sodium; Toxicology

Topics: Acetates; Acid-Base Equilibrium; Acidosis; Amino Acid Metabolism, Inborn Errors; Amino Acids; Blood Chemical Analysis; Butyrates; Child; Citrates; Fumarates; Humans; Infant; Malates; Poisoning; Pyruvates; Renal Aminoacidurias; Salicylates; Succinates; Toxicology; Urine

Topics: Acidosis; Acute Kidney Injury; Alcoholism; Anuria; Child; Diabetes Mellitus; Dialysis; Humans; Hypertension; Hypertension, Malignant; Hyponatremia; Malaria; Peritoneal Dialysis; Poisoning; Renal Dialysis; Renal Insufficiency; Salicylates; Uremia

Topics: Acidosis; Alkalosis; Aspirin; Bicarbonates; Blood Chemical Analysis; Diuretics; Gastric Lavage; Humans; Infusions, Parenteral; Kidney Function Tests; Kidneys, Artificial; Mannitol; Poisoning; Potassium; Renal Dialysis; Salicylates; Sodium; Stomach; Toxicology; Urea; Urinary Catheterization; Urine

Topics: Acidosis; Alkalosis; Electrolytes; Humans; Salicylates

Topics: Acidosis; Animals; Blood; Dogs; Humans; Salicylates; Salicylic Acid

Topics: Acidosis; Benzoates; Edema; Gentisates; Rheumatic Fever; Rheumatic Heart Disease; Salicylates

Topics: Acidosis; Humans; Ketosis; Salicylates