Our search of the literature reveals 1 previous case report of polyuric syndrome in a patient receiving dexmedetomidine.3 In that case, the patient received dexmedetomidine as part of an intraoperative anesthesia regimen at a dose of 0.5 μg/kg/h without a bolus. Elevated serum osmolality and sodium levels resolved within 24 hours of stopping the infusion. In contrast, our patient did not exhibit signs of polyuria until the dose was increased above an infusion rate of 1 μg/kg/h. It is surprising that our patient did not develop hypernatremia despite a urine output in excess of 8 L over 18 hours. Particularly, (as outlined subsequently), dexmedetomidine has been documented to attenuate antidiuretic hormone (ADH) secretion and essentially cause a drug-induced central diabetes insipidus. However, our patient’s urine was not dilute as one would expect if ADH secretion had been suppressed or significantly reduced. In addition, his urine sodium was elevated (Table 1). We feel that the expected reduction in urine osmolality that would be seen with attenuation in ADH secretion was offset by the concomitant infusion of half-normal saline with 5% dextrose that was given during this period, preventing an increase in serum sodium, serum osmolality, or decrease in urine-specific gravity. Other etiologies of polyuria, such as central and nephrogenic diabetes insipidus, primary polydipsia, diuretic administration, and postobstructive diuresis were all unlikely in our case. Our patient had no evidence of intracranial injury affecting the pituitary gland, was not consuming oral fluids, received no diuretics, and had a foley catheter in place. None of the other prescribed medications have been implicated in polyuria (Table 2). Ethanol does have effects on renal function, principally by causing a diuresis of dilute urine via suppression of ADH secretion. However, our patient developed polyuria at a minimum of 72 hours after admission, at which time one would anticipate the ethanol to have been metabolized and the diuretic effect to be negligible. Fortunately, our patient did not develop further renal complications related to alcohol withdrawal such as hypokalemia from renal potassium wasting or acute kidney injury. While we cannot exclude that another undetected phenomenon was responsible for the polyuria, the temporal relationship between the infusion of dexmedetomidine and the dramatic changes in urine output suggests a strong causality.
Dexmedetomidine is an α-2 receptor agonist with 8 times greater affinity for the α-2 adrenoreceptor than clonidine.4 Dexmedetomidine mediates its sedative effects via α-2 receptors in the locus coeruleus.5 Side effects are mediated by central and peripheral actions, and some mechanisms have not been described.6 Multiple animal studies have demonstrated that dexmedetomidine induces polyuria by suppressing vasopressin secretion and increasing permeability of the collecting ducts in a dose-dependent fashion.7–9 Yet, evidence of a similar clinical effect in humans has been rarely reported. Among healthy volunteers, single, high doses of dexmedetomidine decreased norepinephrine and renin levels, but there was no significant change in plasma vasopressin levels.10 We feel that in our case, suppression of vasopressin secretion is the most reasonable explanation for the observed polyuria.
Effects on renal function have not been reported in most studies of dexmedetomidine.11–14 However, in a study of patients undergoing coronary artery bypass grafting, Kulka et al.15 reported preservation of creatinine clearance in patients given clonidine versus placebo. Patients receiving dexmedetomidine as compared with propofol sedation after coronary artery bypass grafting had lower urea and creatinine levels and required less diuretic.16 In another study by Frumento et al.17, thoracic surgery patients receiving adjunctive dexmedetomidine had greater urine output, less diuretic use, and preserved renal function. In contrast, a study of 20 mechanically ventilated ICU patients found no difference in blood urea nitrogen or creatinine levels, or urine output in patients receiving dexmedetomidine compared with propofol.18 In aggregate, these studies suggest no renal harm, and potentially some benefit, with dexmedetomidine.
The dose of dexmedetomidine used was higher than recommended by the United States Food and Drug Administration. Dexmedetomidine has been used with success in patients with alcohol withdrawal,2 and this dose was chosen because our patient had uncontrolled hyperactive alcohol-related delirium on conventional medical therapy. Because there were no adverse hemodynamic or respiratory effects at the time, the dose was titrated in attempts to control his symptoms. Although he developed polyuria, no untoward renal injury occurred, seemingly consistent with the renal outcomes in the study by Frumento et al.17 outlined earlier. It is interesting to note that no adverse hemodynamic effects occurred at this high dose.
In summary, clinicians should be aware that dexmedetomidine has been associated with severe polyuria. The exact mechanism remains to be elucidated, but dexmedetomidine may attenuate the actions of vasopressin. Careful monitoring of urine output and serum sodium levels should be considered in patients receiving dexmedetomidine.
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