The most popular screening test for primary aldosteronism is the plasma aldosterone/renin ratio (ARR). Medications, dietary sodium, posture, and time of day all affect renin and aldosterone levels and can result in false-negative or false-positive ARRs if not controlled. Most antihypertensive medications affect the ARR and can interfere with interpretation of results. To our knowledge, no study has been undertaken to evaluate the effects of moxonidine on the ARR. Normotensive, nonmedicated male volunteers (n = 20) underwent measurement (seated, midmorning) of plasma aldosterone (by high-performance liquid chromatography–tandem mass spectrometry), direct renin concentration (DRC), plasma renin activity (PRA), cortisol, electrolytes and creatinine; and urinary aldosterone, cortisol, electrolytes and creatinine at baseline and after 1 week of moxonidine at 0.2 mg/d and a further 5 weeks at 0.4 mg/d. Compared with baseline, despite the expected significant falls in both systolic and diastolic blood pressure, levels of plasma aldosterone [median, 134 (range, 90 to 535) pmol/L], DRC [20 (10 to 37) mU/L], PRA [2.2 (1.0–3.8) ng/mL/h], and ARR using either DRC [8.0 (4.4 to 14.4)] or PRA [73 (36 to 218)] were not significantly changed after either 1 [135 (98–550) pmol/L, 20 (11–35) mU/L, 2.0 (1.2–4.1) ng/mL/h, 8.8 (4.2 to 15.9), and 73 (32–194), respectively] or 6 weeks [130 (90–500) pmol/L, 22 (8 to 40) mU/L, 2.1 (1.0 to 3.2) ng/mL/h, 7.7 (4.3 to 22.4), and 84 (32 to 192), respectively] of moxonidine. There were no changes in any urinary measurements. Moxonidine was associated with no significant change in the ARR and may therefore be a good option for maintaining control of hypertension when screening for primary aldosteronism.
Metyrapone is an inhibitor of endogenous adrenal corticosteroid synthesis, which has been proven to be a viable option in controlling maternal serum cortisol concentrations during pregnancy. The infant exposure to maternally ingested metyrapone through breast milk is, however, largely unknown. We report the excretion of metyrapone into breast milk and subsequent infant exposure from a lactating woman on 250 mg of metyrapone three times daily. Due to limited supply of breast milk, the infant was fed ∼50% breast milk and 50% formula. At steady state, the average concentrations in the studied breast milk and absolute and relative infant doses were 176 µg/L, 26.45 µg/kg/d, and 0.7%, respectively, for metyrapone, and 310 µg/L, 46.52 µg/kg/d, and 1.21% for its active metabolite metyrapol. The breastfed infant was found to have a plasma metyrapone concentration of 0.05 µg/L, with no evidence of disruption to his adrenocortical axis biochemically. These findings indicate that maternal metyrapone use during breastfeeding did not pose a notable risk to this breastfed infant. The infants’ exposure to metyrapone was further minimized by avoiding nursing for 2 to 3 hours after each metyrapone dose.
Broad-spectrum antibiotics such as beta-lactams and vancomycin are frequently used to treat critically ill patients, however, a significant number do not achieve target exposures. Therapeutic drug monitoring (TDM) combined with Bayesian forecasting dosing software may improve target attainment in these patients. This study aims to describe the efficiency of dosing software for achieving target exposures of selected beta-lactam antibiotics and vancomycin in critically ill patients.A prospective cohort study was undertaken in an adult intensive care unit (ICU). Patients prescribed vancomycin, piperacillin-tazobactam and meropenem were included if they exhibited a subtherapeutic or supratherapeutic exposure informed by TDM. The dosing software, ID-ODS™, was used to generate dosing recommendations which could be either accepted or rejected by the treating team. Repeat antibiotic TDM were requested to determine if target exposures were achieved.Between March 2020 and December 2021, 70 were included in the analysis. Software recommendations were accepted for 56 patients (80%) with 50 having repeated antibiotic measurements. Forty-three of the 50 patients (86%) achieved target exposures after one software recommendation, with 3 of the remaining 7 patients achieving target exposures after 2. Forty-seven patients out of the 50 patients (94%) achieved the secondary outcome of clinical cure. There were no antibiotic exposure-related adverse events reported.The use of TDM combined with Bayesian forecasting dosing software increases the efficiency for achieving target antibiotic exposures in the ICU. Clinical trials comparing this approach with other dosing strategies are required to further validate these findings.
A 35-year-old patient in intensive care with severe burn injury developed episodes of sepsis. Blood culture yielded a multidrug-resistant Pseudomonas aeruginosa and treatment was commenced with amikacin (minimum inhibitory concentration (MIC) 2–4 mg/L, dose 20 mg/kg adjusted body weight 24-hourly) and meropenem (MIC 8 mg/L, dose 2 g IV 8-hourly and later 6-hourly). Despite the use of extended infusions with β-lactam therapeutic drug monitoring and doses that were more than 2.5 times higher than standard meropenem doses, resistance emerged. This case report describes the application of therapeutic drug monitoring to optimize β-lactam therapy in a difficult-to-treat critically ill patient.
Applications of LC-MS/MS for the biochemical diagnosis of catecholamine-producing tumors have followed from parallel emergence of this technology with changes in emphasis of biochemical testing, in particular requirements that testing include measurements of plasma or urinary fractionated metanephrines. Since the turn of the century, when LC-MS/MS was first introduced into the routine laboratory, there have been numerous advances in analytical methodology that offer opportunities for breaking away from out-moded analytical procedures to methods that provide enhanced diagnostic information with dramatically improved analytical sensitivity, accuracy and precision as well as rapid sample throughput. LC-MS/MS also offers high analytical specificity, but is not infallible. Multiple reaction monitoring does not always guarantee selectivity and attention to sample purification and chromatographic separation remains important. Although other analytical methods persist, today LC-MS/MS represents the method of choice for high-throughput, low-cost, precise and accurate measurements of the catecholamine metabolites now routinely used for diagnosis of catecholamine-producing tumors.
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