Benzodiazepines are commonly used sedatives in the ICU and high-dose lorazepam (LOR) has been associated with complications related to propylene glycol (PG). PG levels > 18 mg/dl are potentially toxic. Case series reports suggest that the osmolar gap (OG) is associated with PG levels. This study was undertaken to compare the OG and PG levels.
Adult ICU patients receiving ≥ 1mg/kg/24 hr of LOR were enrolled. Serum osmolality was determined by freezing point depression and OG calculated (measured serum osmolality – calculated osmolality) at enrollment and every other day while receiving LOR. A PG level was obtained when the OG was first ≥ 12 and at discontinuation of LOR. Correlations between drug dose, PG, and OG were determined using the nonparametric spearman test. Data are reported as median (IQR).
14 patients were enrolled. Age was 49 (40–63), 36% were female, APACHE II at start of drug was 16 (14–24), and mortality was 57%. Patients received a total of 631 (437–972) mg LOR for 5.5 (4–8.75) days. 47 OG values were obtained, measuring 8.0 (4.6–11) on day one and 10 (7.8–12) at completion of LOR with maximum OG per patient of 11 (10.25–12). The correlation between OG and PG was 0.66 (p=0.0055), OG and total LOR; 0.65 (p<0.0001), OG and daily LOR; 0.6 (p<0.0001), OG and LOR/KG; 0.61 (p<0.0001), and OG and LOR/KG/DAY; 0.58 (p<0.0001). Of 12 OG values ≥ 10, 11(92%) had PG >18. Of 4 OG < 10 all (100%) had PG <18.CONCLUSIONS: OG correlates with PG levels in adult patients receiving high-dose LOR. OG values ≥ 10 are associated with toxic PG levels.CLINICAL APPLICATIONS: Every other day OG monitoring can predict PG toxicity in patients receiving high dose LOR.
J.A. Yahwak, None.