The impact of environmental temperature on lithium serum levels

Abstract

Objectives: Three studies have reported a seasonal variation in lithium serum levels, with higher levels during summer. Our objective was to investigate the impact of actual environmental temperature on lithium serum levels. Methods: A retrospective study was conducted using available records of lithium serum levels for the period between January 1995 and July 2004, obtained from three large teaching hospitals in The Netherlands. Lithium serum levels were linked to season and average daily temperature data obtained from the Royal Netherlands Meteorological Institute. An analysis was performed on all lithium serum levels not accounting for the intra‐individual dependency of lithium serum levels. The association between season, temperature and both absolute lithium serum level and the frequency of potentially toxic serum levels was investigated. A mixed model analysis, accounting for intra‐individual dependency of lithium serum levels, was performed. Results: A total of 41,102 lithium serum levels (3,054 patients) were included. A significant difference in mean lithium serum levels across seasons (p < 0.001) and temperature categories (p = 0.001) was found, peaking in summer [0.761 mmol/L, ± standard error of the mean (SEM) 0.002] and at temperatures of 15–20°C [0.762 mmol/L (± SEM 0.005)], and at a minimum in winter [0.748 mmol/L (± SEM 0.002)] and at <0°C [0.741 mmol/L (± SEM 0.005)]. The relative frequency of potentially toxic serum levels significantly differed between seasons (p = 0.023, highest in winter), but not between temperature categories (p = 0.481). A significant positive association for intra‐individual lithium serum level and season (p < 0.001) and temperature (p < 0.001) was established. Conclusions: Season and environmental temperature have a statistically significant but therapeutically irrelevant effect on lithium serum levels.

Winter Sale on Lithium Levels: The Impact of Seasonality

“…Perspiration leading to loss of sodium and water from the skin, resulting in a compensatory increased reabsorption of monovalent cations like lithium from the nephrons, is suggested to cause this increased level (21). It has been previously reported that lithium levels can be affected by seasons and temperature (25). In line with this literature, in our study lithium levels were found to be higher in summer without a correlation with sodium levels.…”

Is environmental temperature related to renal symptoms, serum lithium levels, and other laboratory test results in current lithium users?

“…However, we did not observe this association when using our main temperature outcome measure ( T > 20°C) or when performing geriatric/adult subgroup analyses. A large study in the Netherlands also found a statistically significant but clinically unimportant association between temperature and lithium levels (Wilting et al ., ). Still, in countries that often had temperatures >30°C, intra‐individual lithium level variability between the coldest and warmest months approached 25% (Medhi et al ., ).…”

“…Geriatric and adult patients were compared for clinical and demographic variables using chi‐squared, Fisher's exact, Student's t , and Mann–Whitney U tests, as appropriate. Mann–Whitney U , chi‐squared tests, and Spearman bivariate correlations were performed between environmental temperature (temperature >20°C and continuous temperature variable) and potential correlates: self‐reported symptoms of diabetes insipidus (liquid intake, thirst severity, urinary symptom severity, daytime and night‐time urinary frequency, painful urination, hypernatremia symptoms, and functional impairment due to thirst/urination), eGFR (Lee et al ., ), urine osmolality (Rej et al ., ), serum sodium (Adrogue and Madias, ), lithium level (D'Mello et al ., ; Beersma et al ., ; Cusin et al ., ; Wilting et al ., ; Medhi et al ., ), or lithium dose–level ratio (Sproule et al ., ). The Spearman correlation between lithium dose–level ratio and temperature was also tested in adults and geriatric patients separately, because older adults have been postulated to have a higher risk of lithium toxicity at elevated temperatures (Weinstein and Anderson, ).…”

“…Our exposure of interest was mean environmental temperature (or “temperature”), using (1) a dichotomous temperature threshold of 20°C used in previous studies (Wilting et al ., ) and (2) temperature as a continuous variable. We defined temperature as the average of the highest and lowest daily recorded temperatures in Montreal or Toronto on the questionnaire or laboratory testing date, as applicable.…”

“…However, whether serum lithium levels are affected by patients' environmental temperature remains unclear. Although four moderately sized studies ( n = 68–337) have found that lithium levels vary by 5–25% between the coldest and hottest seasons of the year (D'Mello et al ., ; Beersma et al ., ; Cusin et al ., ; Medhi et al ., ), a large population‐based study found no relationship between lithium levels and temperature (Wilting et al ., ). To date, however, no study has assessed the association between environmental temperature and the ratio between lithium dose and serum level.…”