Dexmedetomidine is a selective alpha-2 adrenergic agonist that is used as a sedative in the ICU. Emerging postoperative studies indicate that the parenteral agent may be renoprotective. While the exact mechanism by which dexmedetomidine exerts its renal-protective effect is not known, it is thought to be related to the drug's sympatholytic, anti-inflammatory, and cytoprotective properties.
Researchers conducted a systematic review and meta-analysis to characterize the use of dexmedetomidine and to evaluate its impact on renal markers and outcomes in postsurgical patients.
English-language placebo-controlled studies in which dexmedetomidine was administered following surgery were identified in PubMed, Embase, and Cochrane databases.
Study endpoints, which were collected 24 hours after dexmedetomidine administration, included markers of renal function (i.e., serum blood urea nitrogen, serum creatinine, creatinine clearance, neutrophil gelatinase-associated lipoprotein [NGAL], cystatin C, urine output, acute kidney injury, need for dialysis), duration of mechanical ventilation, ICU length of stay, and inpatient mortality. NGAL, also known as lipocalin-2, is a secreted glycoprotein that acts as a transporter for small lipophilic molecules and serves as a marker of acute kidney injury. Cystatin C, a protein that is filtered by the glomerulus, reabsorbed, and broken down by the renal tubules for recycling, correlates closely with the glomerular filtration rate.
Nineteen studies involving 3,395 patients (of whom 1,683 patients received dexmedetomidine) were included in the final pooled analyses. Sixteen of these trials were prospective, randomized, placebo-controlled studies. The average age of study participants ranged from 56.2 years in the dexmedetomidine group to 59.8 years in the control group. Three of the included studies involved pediatric patients. Almost 80% of the studies involved the use of dexmedetomidine during surgery, whereas the rest involved the use of the alpha agonist either following surgery or in critically ill patients. The mean bolus dose of dexmedetomidine utilized was 0.82 mcg/kg, and the mean infusion dose was 0.54 mcg/kg/hour.
The investigators found that there were statistically significant differences in ICU length of stay (reduced by 0.45 days), creatinine clearance (4.22 mL/min/1.73m2 higher), NGAL (reduced by 25.18 ng/mL), inpatient mortality (risk reduced by 52%; relative risk of 0.48), and acute kidney injury (risk reduced by 57%; relative risk of 0.43) between the intervention and control groups. The number-needed-to-treat was 30.3 for inpatient mortality and 17.6 for acute kidney injury. However, there were no differences between the intervention and control groups in duration of mechanical ventilation, urine output, serum creatinine, blood urea nitrogen, cystatin C concentrations, or need for dialysis after dexmedetomidine.
The authors also indicated that the use of dexmedetomidine is cost-effective compared with the expense incurred to treat acute kidney injury or to prevent a single inpatient death.
For pharmacists managing ICU patients, this study provides encouraging results that dexmedetomidine may be helpful in maintaining renal function during periods of hemodynamic instability.
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