Drug-induced acid-base disorders
Daniel Kitterer
0
Matthias Schwab
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M. Dominik Alscher
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Niko Braun
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Joerg Latus
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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).
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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)