Hypokalaemia, Metabolic Alkalosis, and Hypernatraemia due to "Massive" Sodium Penicillin Therapy

Brunner, F; Pg, Frick

doi:10.1136/bmj.4.5630.550

Cited by 78 publications

(21 citation statements)

References 13 publications

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“…This is noteworthy given that hypokalemia was the most common adverse event identified in our study. Drug-induced hypokalemia is related to nonabsorbable ion effects in the distal tubule and/or intracellular redistribution due to volume depletion (22)(23)(24)(25). The available literature suggests that this occurs rarely after instituting therapy with penicillin-type antimicrobials (22,25).…”

Section: Discussionmentioning

confidence: 99%

Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin

Viehman

Oleksiuk

Sheridan

et al. 2016

Antimicrob Agents Chemother

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b Nafcillin and oxacillin are used interchangeably in clinical practice, yet few studies have evaluated the safety of these two agents. Our objective was to compare the differential tolerabilities of nafcillin and oxacillin among hospitalized patients. We conducted a retrospective cohort study of all patients who received 12 g/day of nafcillin or oxacillin for at least 24 h. Two hundred twentyfour patients were included. Baseline characteristics and comorbidities were similar among patients receiving nafcillin (n ‫؍‬ 160) and those receiving oxacillin (n ‫؍‬ 64). Hypokalemia, defined as a potassium level of <3.3 mmol/liter or <2.9 mmol/liter or as a >0.5-mmol/liter decrease from the baseline level, occurred more frequently among patients who received nafcillin (51%, 20%, and 56%, respectively) than among those who received oxacillin (17%, 3%, and 34%, respectively; P < 0.0001, P ‫؍‬ 0.0008, and P ‫؍‬ 0.005, respectively). By multivariate logistic regression analysis, receipt of nafcillin was an independent predictor of severe hypokalemia (odds ratio [OR] ‫؍‬ 6.74; 95% confidence interval [CI], 1.46 to 31.2; P ‫؍‬ 0.02). Rates of hepatotoxicity did not differ between groups; however, acute kidney injury occurred more commonly with nafcillin than with oxacillin (18% versus 6%; P ‫؍‬ 0.03). Overall, 18% of patients who received nafcillin discontinued therapy prematurely due to adverse events, compared to 2% of patients who received oxacillin (P ‫؍‬ 0.0004). Nafcillin treatment is associated with higher rates of adverse events and treatment discontinuation than oxacillin among hospitalized adult patients. These findings have important implications for patients in both inpatient and outpatient settings, particularly patients who require long-term therapy and cannot be monitored routinely. Future randomized controlled studies evaluating the efficacy, costs, and tolerability of nafcillin versus oxacillin are warranted.

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Section: Discussionmentioning

confidence: 99%

Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin

Viehman

Oleksiuk

Sheridan

et al. 2016

Antimicrob Agents Chemother

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“…Hypokalemia has been reported in patients receiving penicillin derivatives [165]. It has been suspected that penicillins act as nonreabsorbable anions, which maintain a transmembrane potential gradient that is negative on the lumen side in the cortical collecting duct, while the delivery of Cl − ions in the distal collecting duct is reduced (Fig.…”

Section: Penicillinsmentioning

confidence: 99%

Drug-induced acid-base disorders

et al. 2014

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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

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“…In earlier studies in two patients with Lowe's syndrome, a relative volume contraction was found to influence acid-base equilibrium [14]; in man, plasma volume was shown to be inversely related to renal bicarbonate threshold. In patients with hypokalemic alkalosis, ECF volume may play a major role in the genesis of the disorder, as it probably did in the patients treated with massive doses of sodium penicillin by Brunner and Frick [3]. The observation by Houston et al [9], in a patient with the Fanconi syndrome, that metabolic alkalosis was not completely correctable by sodium supplements (correction of volume) alone points to the role of potassium as a factor influencing renal handling of hydrogen ion.…”

Section: Introductionmentioning

confidence: 92%

Hypokalemia, a Factor Influencing Renal Bicarbonate Reabsorption: Continued Studies on the Regulatory Mechanisms Governing Renal Handling of Acid-Base in Children

et al. 1971

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ExtractIn a program concerned with regulatory mechanisms influencing the renal contribution to acid-base balance in pediatric-aged subjects, two patients with hypokalemic alkalosis were studied. The relation of scrum potassium level to proximal tubular bicarbonate reabsorption was assessed at different potassium levels during states of equal plasma volumes or equal extracellular fluid (ECF) volumes. Renal bicarbonate threshold was cither determined by means of bicarbonate titration studies or estimated from urinary pH and simultaneous plasma bicarbonate concentration. Estimation of threshold was judged to be acceptable if pH values in urine were close to 6.2, thereby indicating little or no spilling of bicarbonate into the urine. Simultaneous plasma bicarbonate concentrations indicated renal bicarbonate threshold.Patient NAI exhibited a renal bicarbonate threshold of 25 mmoles/liter at a serum potassium level of 1.7 mval/liter and 20.5 mmoles/liter at a potassium level of 2.7 mval/liter. Plasma volume was 54.7 and 52.9 ml/kg body weight, respectively.Patient BE showed a renal bicarbonate threshold of 24.3 mmoles/liter with an ECF volume of 474 ml/kg body weight and a serum potassium level of 1.7 mval/ liter; however, this patient exhibited a renal bicarbonate threshold of less than 21 mmoles/liter with an ECF volume of 454 ml/kg body weight and a potassium level of 3.2 mval/liter.In both patients, renal bicarbonate threshold decreased when serum potassium levels increased. Moreover, plasma volume in one patient and ECF volume in the other either had decreased slightly or had remained essentially unchanged. Hence, an indirect relation was found between serum potassium level and renal bicarbonate threshold. Plasma volume, known to influence renal bicarbonate threshold, was without effect on this relation. SpeculationIn hypokalemic alkalosis the level of serum potassium itself or the levels of serum potassium as indicators of whole body potassium might be among the factors influencing renal bicarbonate reabsorption. 618Hypokalemia and renal bicarbonate reabsorption 619

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Hypokalaemia, Metabolic Alkalosis, and Hypernatraemia due to "Massive" Sodium Penicillin Therapy

Cited by 78 publications

References 13 publications

Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin

Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin

Drug-induced acid-base disorders

Hypokalemia, a Factor Influencing Renal Bicarbonate Reabsorption: Continued Studies on the Regulatory Mechanisms Governing Renal Handling of Acid-Base in Children

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