Effect of high-dose sulfamethoxazole/trimethoprim and glucocorticoid use on hyperkalemic event: A retrospective observational study

Hirai, Toshinori; Yamaga, Ryosuke; Ishikawa, Yutori; Hanada, Kazuhiko; Iwamoto, Takuya; Itoh, Toshimasa

doi:10.1016/j.jiac.2021.07.011

Cited by 7 publications

(9 citation statements)

References 29 publications

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“…31,32 Hirai et al reported that low-dose TMP treatment (< 320 mg) with glucocorticoids significantly reduces the risk of hyperkalemia compared with that in untreated individuals. 33 Our results also support their findings. Renin-angiotensin system inhibitors, calcineurin inhibitors, and potassium-sparing diuretics are known to increase K + concentrations, whereas amphotericin B and loop diuretics are known to decrease K + concentrations.…”

Section: Resultssupporting

confidence: 90%

“…However, glucocorticoid administration has been reported to cause an acute transient kaliuresis, which may be a direct result of increased GFR, and thereby lead to increased sodium delivery to the distal nephron 31,32 . Hirai et al reported that low‐dose TMP treatment (< 320 mg) with glucocorticoids significantly reduces the risk of hyperkalemia compared with that in untreated individuals 33 . Our results also support their findings.…”

Section: Discussionsupporting

confidence: 88%

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Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Yokoyama

Nakagawa

Aiuchi

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective: Trimethoprim (TMP) inhibits the Na + /K + -ATPase present in the basement membrane of distal tubular epithelial cells. However, hyponatremia and hyperkalemia may develop in patients taking TMP-sulfamethoxazole (SMX). In addition, because TMP inhibits drug transporters, such as organic cation transporter 2 and multidrug and toxin extrusion protein 2-K in proximal tubules, reversible increases in the concentration of serum creatinine (SCr), the substrate of these transporters, may occur. Here, we investigated variability in SCr, serum sodium (Na + ), and serum potassium (K + ) concentrations after initiation of TMP-SMX treatment and evaluated the risk of hyponatremia and hyperkalemia in patients with increased SCr concentrations without changes in the glomerular filtration rate (GFR).Methods: In this retrospective study, all patients aged 20 years or older who received oral TMP-SMX during hospitalization were enrolled. The patients with estimated creatinine (Cr) clearance (eCCr) lower than 30 mL/min were excluded, as were patients taking drugs that were likely to induce renal dysfunction, drugs other than glucocorticoids that were likely to induce electrolyte imbalances, or drugs other than TMP that inhibit tubular Cr secretion. Additionally, those with SCr concentrations elevated more than 30% from baseline or serum blood urea nitrogen concentration levels above 20 mg/dL during follow-up were also excluded.Results and Discussion: In total, 111 patients were enrolled in the study. The common independent variable affecting the change rate in SCr, Na + , and K + concentrations (ΔSCr, ΔNa + , and ΔK + ) from baseline to the highest value during the follow-up period (14 days after initiation of TMP-SMX treatment) was the daily dose of TMP.There were significant correlations between ΔSCr and ΔNa + or ΔK + (ρ = À0.199, p = 0.036 and ρ = 0.244, p = 0.010, respectively). Kaplan-Meier curves for hyponatremia and hyperkalemia with greater than or equal to grade 1 severity showed different profiles when the TMP dose varied (≤ 160 vs. > 160 mg/day; p = 0.005 and 0.008). The cumulative incidences of both adverse effects were 64.7% (median: 7 days) and 29.4% in patients taking more than 160 mg/day TMP and 35.2% and 6.7% in patients taking 160 mg/day TMP or less. Thus, TMP may affect the kinetics of Cr, Na + , and K + in the proximal and distal tubules in a dose-dependent without changing the GFR.

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Section: Resultssupporting

confidence: 90%

Section: Discussionsupporting

confidence: 88%

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Yokoyama

Nakagawa

Aiuchi

et al. 2022

Clinical Pharmacy Therapeu

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“…Thus, the elevation of C u in renal impairment was largely offset by the decline of renal function. The relationship between renal function and hyperkalaemia risk remains controversial, as reported in many studies 6,9,30 . Our potassium model was based on renal function.…”

Section: Discussionmentioning

confidence: 99%

Population kinetic–pharmacodynamic analysis of serum potassium in patients receiving sulfamethoxazole/trimethoprim

Hirai

Shiraishi

Nakai

et al. 2022

Basic Clin Pharma Tox

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Since trimethoprim (TMP) dose-dependently inhibits the excretion of potassium, a population kinetic-pharmacodynamic analysis was performed to establish an adequate dosing schedule and characterize factors of hyperkalaemia. Dataset was constructed using a retrospective observational cohort of hospitalized patients (>18 years) with oral sulfamethoxazole/trimethoprim formulation. The model integrated a kinetic model for TMP, a urinary TMP concentrationresponse curve and a kinetic model for serum potassium using an indirect response model. The model was a function of body weight, renal function, serum potassium levels and TMP dosing schedule. We evaluated covariates by the stepwise forward and backward selection methods. The Monte Carlo simulation determined the probability of hyperkalaemia (>5.5 or >6.0 meq/L) according to the dosing schedule, renal function and covariates. This study included 317 patients [age 62 (42-72) years] with 4359 serum potassium levels.The significant covariate was non-steroidal anti-inflammatory drugs (NSAIDs), with a 72.3% reduction in 50% inhibitory concentration. Monte Carlo simulation revealed that high-dose TMP (400 mg thrice daily) co-administered with NSAIDs led to mild hyperkalaemia (>10%) and severe hyperkalaemia (approximately 5%), regardless of renal function. In conclusion, clinicians should pay attention to hyperkalaemia with TMP high-dose and co-administered NSAIDs.

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“…This is likely to indicate that preoperative potassium disturbances in elderly hospitalized patients with normal renal function are more manifested as hypokalemia. Other drugs such as Yokukansan [ 37 ], sulfamethoxazole/trimethoprim [ 25 ], and licorice [ 39 ] also cause blood potassium disorder by affecting excretion. However, due to the low proportion of patients taking these drugs, it was difficult to compare their effects on preoperative hypokalemia.…”

Section: Discussionmentioning

confidence: 99%

“…Hyperkalemia refers to a serum potassium concentration > 5.5 mmol/L. [25] mortality were not increased, which may be related to monitoring blood gas analysis and prompt correction of potassium levels during surgery.…”

Section: Criteria Of Hypokalemiamentioning

confidence: 99%

Association between preoperative hypokalemia and postoperative complications in elderly patients: a retrospective study

Chu

2022

BMC Geriatr

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Background Hypokalemia is a common form of electrolyte disorder, which has a higher incidence in hospitalized patients and is closely related to perioperative complications and prognosis. Due to decreased skeletal muscle mass which causes total body potassium reduction, and increased comorbidities, the elderly are more susceptible to hypokalemia. Objective To investigate preoperative hypokalemia in elderly patients and its effect on postoperative complications. Methods Data were retrospectively collected from the elderly patients who underwent elective surgery from April 2018 to March 2019 and had preoperative blood gas data available. Patients, with age 60 to 100 years, were divided into hypokalemia group (potassium level < 3.5 mmol/L) and normokalemia group (potassium level between 3.5 and 5.5 mmol/L) according to preoperative blood gas analysis. Hypokalemia can be divided into mild (potassium level 3.0 to 3.5 mmol/L), moderate (potassium level 2.5 to 3.0 mmol/L) and severe (potassium level < 2.5 mmol/L), respectively. The risk factors of preoperative hypokalemia and its impact on postoperative complications and prognosis were primary outcomes. Secondary outcomes included postanesthesia care unit (PACU) stay time and hospital length of stay (LOS). Results Of 987 participants, 436 (44.17%) developed preoperative hypokalemia, among them 357 (81.88%) mild, 87 (16.74%) moderate and 6 (1.38%) severe. Multivariate logistic regression showed that female gender (OR, 1.851; 95% CI, 1.415–2.421), pre-existing hypokalemia at admission (OR, 4.498; 95% CI, 2.506–8.071), and oral laxative twice or more (OR, 1.823; 95% CI, 1.266–2.624) are risk factors of preoperative hypokalemia. Gynecological and biliopancreatic surgery were more common in hypokalemia group than normokalemia group (P < 0.001, P < 0.05). There was no significant difference in postoperative complications, PACU stay time, LOS, and 30-day mortality between the two groups (all P > 0.05). Conclusions Female gender, pre-existing hypokalemia at admission, and oral laxative twice or more are independent risk factors for preoperative hypokalemia in elderly patients. However, postoperative complications and 30-day mortality were not increased, which may be related to monitoring blood gas analysis and prompt correction of potassium levels during surgery.

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Effect of high-dose sulfamethoxazole/trimethoprim and glucocorticoid use on hyperkalemic event: A retrospective observational study

Cited by 7 publications

References 29 publications

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Impact of trimethoprim on serum creatinine, sodium, and potassium concentrations in patients taking trimethoprim‐sulfamethoxazole without changes in glomerular filtration rate

Population kinetic–pharmacodynamic analysis of serum potassium in patients receiving sulfamethoxazole/trimethoprim

Association between preoperative hypokalemia and postoperative complications in elderly patients: a retrospective study

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