Drug-induced acid-base disorders

Pediatric Nephrology, Sep 2015

The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal anti-inflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk–alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g., anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine, nicotine).

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Drug-induced acid-base disorders

Daniel Kitterer 0 Matthias Schwab 0 M. Dominik Alscher 0 Niko Braun 0 Joerg Latus 0 0 M. Schwab Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology , Stuttgart, Germany , and Department of Clinical Pharmacology, University Hospital , Tuebingen , Germany The incidence of acid-base disorders (ABDs) is high, especially in hospitalized patients. ABDs are often indicators for severe systemic disorders. In everyday clinical practice, analysis of ABDs must be performed in a standardized manner. Highly sensitive diagnostic tools to distinguish the various ABDs include the anion gap and the serum osmolar gap. Drug-induced ABDs can be classified into five different categories in terms of their pathophysiology: (1) metabolic acidosis caused by acid overload, which may occur through accumulation of acids by endogenous (e.g., lactic acidosis by biguanides, propofol-related syndrome) or exogenous (e.g., glycol-dependant drugs, such as diazepam or salicylates) mechanisms or by decreased renal acid excretion (e.g., distal renal tubular acidosis by amphotericin B, nonsteroidal antiinflammatory drugs, vitamin D); (2) base loss: proximal renal tubular acidosis by drugs (e.g., ifosfamide, aminoglycosides, carbonic anhydrase inhibitors, antiretrovirals, oxaliplatin or cisplatin) in the context of Fanconi syndrome; (3) alkalosis resulting from acid and/or chloride loss by renal (e.g., diuretics, penicillins, aminoglycosides) or extrarenal (e.g., laxative drugs) mechanisms; (4) exogenous bicarbonate loads: milk-alkali syndrome, overshoot alkalosis after bicarbonate therapy or citrate administration; and (5) respiratory acidosis or alkalosis resulting from drug-induced depression of the respiratory center or neuromuscular impairment (e.g., anesthetics, sedatives) or hyperventilation (e.g., salicylates, epinephrine, nicotine). - Acid-base disorders (ABDs) are frequently present in hospitalized patients and are often a manifestation of systemic disorders. Analysis of ABDs must be performed in a standardized manner. Calculating the serum anion gap (AG) is the first step to differentiate between ABDs [15]. The AG must be corrected for serum albumin levels, and it must be considered that several factors (e.g., paraproteinemia, lithium, and bromide intoxication; hypercalcemia; hypermagnesemia; syndrome of inappropriate antidiuretic hormone secretion (SIADH); severe hyperphosphatemia), as well as the laboratory measurement method used [1], could interfere with the calculation. Clinical information, including medical history and laboratory data, must be obtained from the patient, especially in differentiating possible mixed acid-base disturbances. The urine AG (UAG) is a useful tool for differentiating ABDs, especially in patients with metabolic acidosis with normal serum AG. UAG can be used as a parameter for acid excretion by the kidney: ([urine sodium ions (Na+)]+[urine potassium ions (K+)]) [urine chloride (Cl)]), normal range 10 to + 10 mmol/L). A negative UAG (average 15 mmol/l) indicates an increased ammonium (NH4+) excretion (e.g., diarrhea) in metabolic acidosis with normal serum AG. In such cases, positive UAG (>20 mmol/l) indicates a low urinary NH4+ excretion [altered distal urinary acidification, e.g., altered renal tubular acidosis (RTA)]. It should be noted that UAG is influenced by exogenous anions (ketonuria, penicillins, and high doses of acetylsalicylic acid). In patients with positive UAG, determining urine pH could help distinguish between the different types of RTA: type 1 is characterized by a fixed urine pH of >5.5 and decreased or normal serum K+ levels; type 2 by urine pH levels <5.5; and type 4 commonly by hyperkalemia and urine pH levels <5.5 (Fig. 1). The AG can be calculated using the simplified formula [Na+] ([Cl] + [bicarbonate (HCO3)]) (normal range, 3 11 mEq/L), measured with ion-selective electrodes, up to 18 mEq/L in newborns; if serum K+ is included in AG measurement, normal range is ~4 mEq/L higher [1, 69]. It is noteworthy that the AG depends on plasma albumin levels, and hypoalbuminemia is a common finding in hospitalized patients. A decrease of 1.0 g/dl (from 4.5 g/dl) of albumin concentration decreases the AG by roughly 2.5 mEq/L [1012]. Increased AG indicates acid overload caused by ketoacidosis, lactic acidosis, uremia, salicylates, methanol, or ethylene glycol intoxication. If there is an increased AG, the osmolar gap (OG), defined as the difference between measured and calculated serum osmolality, should be calculated to detect methanol or ethylene glycol intoxication, which will result in an increased OG ([2 Na+glucose]/18)+(blood urea nitrogen [BUN/2.81]); correction factors for calculating the OG are only required in if nonstandard units (i.e., mg/dl) are used. However, simple alcohol (ethanol) intoxication with lactate acidosis can resemble changes [13]. The normal OG range is wide in children (from+8.9 to 13.5 mOsm/L), but intoxication must be considered when the OG is (...truncated)


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Daniel Kitterer, Matthias Schwab, M. Dominik Alscher, Niko Braun. Drug-induced acid-base disorders, Pediatric Nephrology, 2015, pp. 1407-1423, Volume 30, Issue 9, DOI: 10.1007/s00467-014-2958-5