Salicylate respiratory alkalosis with

This patient had ingested a large quantity of aspirin resulting in the classic findings of a salicylate overdose a centrally mediated respiratory alkalosis with a concurrent anion gap metabolic acidosis. 

Mixed metabolic acidosis and respiratory alkalosis occur in patients with advanced liver disease, salicylate intoxication, and pulmonary-renal syndromes. 

On the other hand, primary respiratory alkalosis occurs as a result of alveolar hyperventilation. This condition is associated with a number of pulmonary diseases, bui also may appear during pregnancy, liver disease, and salicylate intoxication, among others. The sequence of events proceeds along these lines (I) Ventilation removes CO faster than the gas is produced by metabolism, causing a decrease tn pCO in the blood and body fluids, including a reduction of venous pCO . This reduces the gradient... 

Acetazolamide can cause a metabolic acidosis in 50% of elderly patients (SEDA-11,199) occasionally (particularly if salicylates are being given or renal function is poor) the acidosis can be severe. It does this by inhibiting renal bicarbonate reabsorption. This effect is of particular use in treating patients with chronic respiratory acidosis with superimposed metabolic alkalosis. Life-threatening metabolic acidosis is rarely observed in the absence of renal insufficiency and/or diabetes mellitus. In three patients with central nervous system pathology alone conventional doses of acetazolamide resulted in severe metabolic acidosis (34). After withdrawal it took up to 48 hours for the metabolic acidosis and accompanying hyperventilation to resolve. 

Animals may manifest toxicity to salicylates with signs and symptoms similar to those seen in humans. These may include fever, hyperpnea, seizures, respiratory alkalosis, metabolic acidosis, gastric hemorrhage, and kidney damage. Methemoglobinemia has also been seen in animals following salicylate toxicity. Activated charcoal has been used in animals. Methylene blue or ascorbic acid may be utilized for the treatment of methemoglobinemia. 

Adults and older children tend to correct the disturbance at this point. Young children, however, quickly develop a fall in the blood pH (metabolic acidosis), due to salicylate stimulation of metabolism. The toxic effects of salicylate and the loss of buffer base interfere with metabolic processes, and ketosis develops. Because the respiratory alkalosis and metabolic acidosis occur simultaneously, a child may present with a mixed disturbance and a relatively normal pH, or with frank acidosis. The PC02 will be lower than expected. Children < 4 yr develop metabolic acidosis more rapidly, without concurrent respiratory alkalosis. Dehydrationj is a serious problem because of insensible water loss and increased renal water loss (from an increased urine solute load). Severe losses of sodium and potassium are not uncommon (15). 

The primary acid-base disturbance observed with salicylate overdosage depends on age and severity of intoxication. Respiratory alkalosis predominates in children over age 4 and in adults, except in very severe cases that may progress through a mixed respiratory alkalosis-metabolic acidosis to metabolic acidosis. In 97 adult patients who had plasma salicylate concentrations greater than 700mg/L, 19% were found to have respiratory alkalosis, 61% had combined res-... 

This generally occurs with blood salicylate concentrations above 30 mg/dL. Salicylate, itself an unmeasured anion, alters peripheral metabolism, leading to the production of various organic acids without dominance of any specific acid. The processes eventually result in a metabohc acidosis with a high anion gap. Saficylate also stimulates the respiratory center to increase the rate and depth of respiration, resulting in a low PCO2, low HCOj, and respiratory alkalosis (see the section entitled Respiratory Alkalosis). In adults, mijced respiratory aUcalosis and metabolic acidosis are more common, whereas in children, metabolic acidosis predominates. 

This mixed disorder is often seen in patients with advanced liver disease, salicylate intoxication, and pulmonary-renal syndromes. The respiratory alkalosis decreases the PaC02 beyond the appropriate range of the respiratory compensation for metabolic acidosis. The plasma bicarbonate concentration also falls below the level expected in compensation for a simple respiratory alkalosis. In a sense, the defense of pH for either disorder alone is enhanced thus the pH may be normal or close to normal, with a low PaC02 and a low [HCOj]. Treatment of this disorder should be directed at the underlying cause. Because of the enhanced compensation, the pH is usually closer to normal than in either of the two simple disorders. 

Salicylate poisoning is associated with a metabolic acidosis and a respiratory alkalosis due to the direct effect of salicylate on the respiratory centre. The [H ] and PCO indicate that the respiratory alkalosis is dominant at this stage in the patient. 

Where the two acid-base conditions arc antagonistic in the way they affect the [H. one of the disorders may mimic the compensatory response. A patient may present with a metabolic acidosis and a co-existent respiratory alkalosis, as occurs commonly in salicylate overdose. The respiratory disorder may appear, at first sight, to be simply the compensatory response. 

Overdosage of salicylate causes metabolic acidosis with respiratory alkalosis hyperpnea and tachypnea are caused by increased CO2 production and direct stimulation of the respiratory center. 

As described above, high therapeutic doses of salicylate are associated with a primary respiratory alkalosis and compensatory renal acidosis. Subsequent changes in acid—base status generally occur only when toxic doses of salicylates are ingested by infants and children or occasioncdly after large doses in adults. 

The phase of primary respiratory alkalosis rarely is recognized in children with salicylate toxicity. They usually present in a state of mixed respiratory and renal acidosis, characterized by a decrease in blood pH, a low plasma bicarbonate concentration, and normal or nearly normal plasma PCO2. Direct salicylate-induced depression of respiration prevents adequate respiratory hyperventilation to match the increased peripheral production of CO2- Consequently, plasma PCO2 increases and blood pH decreases. Because the concentration of bicarbonate in plasma already is low due to increased renal bicarbonate excretion, the acid-base status at this stage essentially is an uncompensated respiratory acidosis. Superimposed, however, is a true metabolic acidosis caused by accumulation of acids as a result of three processes. First, toxic concentrations of salicylates displace 2-3 mEq/L of plasma bicarbonate. Second, vasomotor depression caused by toxic doses of salicylates impairs renal function, with consequent accumulation of sulfuric and phosphoric acids. Third, salicylates in toxic doses may decrease aerobic metabolism as a result of inhibition of various enzymes. This derangement of carbohydrate metabolism leads to the accumulation of organic acids, especially pyruvic, lactic, and acetoacetic acids. 

Respiratory alkalosis is associated with many illnesses. Hyperventilation has several causes. The CNS respiratory centre is stimulated by many factors including anxiety, psychosis, pain and fever. Overdosage of salicylates can initially stimulate ventilation causing respiratory alkalosis which may be followed by metabolic acidosis. Stimulation of the chest receptors by conditions such as pneumothorax, pulmonary embolism and pulmonary oedema can cause hyperventilation and hypocapnia. Other causes include mechanical ventilation, hepatic failure and sepsis... 

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