Hypoglycaemia incidence with a simple, low-dose insulin protocol for adult diabetic ketoacidosis.

OBJECTIVE: The objective of this study is to validate the glycaemic safety of a simple insulin protocol using weight-based insulin rates adapted from American guidance for the management of adult diabetic ketoacidosis. METHODS: Measures of hypoglycaemia were retrospectively assessed in a single cohort of inpatient adults. The primary outcome was incidence of hypoglycaemia during insulin infusion. KEY FINDINGS: Hypoglycaemia during infusion occurred in 6/81 patients (7% [95% CI 3-16%]). Five of these occurrences were associated with protocol nonadherence. CONCLUSIONS: The glycaemic safety of a novel, variable-rate insulin protocol directly incorporating weight-based infusion rates is supported by this single-centre study.

Communication Training, Adverse Events, and Quality Measures: 2 Retrospective Database Analyses in Washington State Hospitals.

OBJECTIVE: Washington State's HealthPact program was launched in 2011 as part of AHRQ's Patient Safety and Medical Liability Reform initiative. HealthPact delivered interdisciplinary communication training to health-care professionals with the goal of enhancing safety. We conducted 2 exploratory, retrospective database analyses to investigate training impact on the frequency of adverse events (AEs) and select quality measures across 3 time frames: pretraining (2009-2011), transition (2012), and posttraining (2013). METHODS: Using administrative data from Washington State's Comprehensive Hospital Abstract Reporting System (CHARS) and clinical registry data from the Surgical Care and Outcomes Assessment Program (SCOAP), we compared proportions of AEs and quality measures between HealthPact (n = 4) and non-HealthPact (n = 93-CHARS; n = 48-SCOAP) participating hospitals. Risk ratios enabled comparisons between the 2 groups. Multivariable logistic regression enabled investigation of the association between training and the frequency of AEs. RESULTS: Approximately 9.4% (CHARS) and 7.7% (SCOAP) of unique patients experienced 1 AE or greater. In CHARS, the odds of a patient experiencing an AE in a HealthPact hospital were initially (pretraining) higher than in a non-HealthPact hospital (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.10-1.17), lower in transition (OR, 0.80; 95% CI, 0.76-0.83) and posttraining (OR, 0.72; 95% CI, 0.69-0.75) periods. In SCOAP, ORs were consistently lower in HealthPact hospitals: pretraining (OR, 0.87; 95% CI, 0.80-0.95), transition (OR, 0.75; 95% CI, 0.70-0.81), and posttraining (OR, 0.63; 95% CI, 0.58-0.68). The proportion of at-risk patients that experienced each individual AE was low (<1%) throughout. Adherence to quality measures was high. CONCLUSIONS: Interprofessional communication training is an area of intense activity nationwide. A broad-based training initiative may play a role in mitigating AEs.

Effect of N-Acetyltransferase 2 Genotype on the Pharmacokinetics of Hydralazine During Pregnancy.

Hydralazine, an antihypertensive agent used during pregnancy, undergoes N-acetylation primarily via N-acetyltransferase 2 (NAT2) to form 3-methyl-1,2,4-triazolo[3,4-a]phthalazine (MTP). To characterize the steady-state pharmacokinetics (PK) of hydralazine during pregnancy and evaluate the effects of NAT2 genotype on hydralazine and MTP PK during pregnancy, 12 pregnant subjects received oral hydralazine (5-25 mg every 6 hours) in mid- (n = 5) and/or late pregnancy (n = 8). Serial blood samples were collected over 1 dosing interval, and steady-state noncompartmental PK parameters were estimated. Subjects were classified as either (rapid acetylators, n = 6) or slow acetylators (SAs, n = 6) based on NAT2 genotype. During pregnancy, when compared with the SA group, the RA group had faster weight-adjusted hydralazine apparent oral clearance (70.0 ± 13.6 vs 20.1 ± 6.9 L/h, P < .05), lower dose-normalized area under the concentration-time curve (AUC; 1.5 ± 0.8 vs 5.9 ± 3.7 ng·h/mL, P < .05), lower dose-normalized peak concentrations (0.77 ± 0.51 vs 4.04 ± 3.18 ng/mL, P < .05), and larger weight-adjusted apparent oral volume of distribution (302 ± 112 vs 116 ± 45 L/kg, P < .05). Furthermore, the MTP/hydralazine AUC ratio was ∼10-fold higher in the RA group (78 ± 30 vs 8 ± 3, P < .05) than in the SA group. No gestational age or dose-dependent effects were observed, possibly because of the small sample size. This study describes for the first time, the PK of oral hydralazine and its metabolite, MTP, during pregnancy, and confirmed that the PK of oral hydralazine is NAT2 genotype dependent during pregnancy.

Fixed-rate insulin for adult diabetic ketoacidosis is associated with more frequent hypoglycaemia than rate-reduction method: a retrospective cohort study.

OBJECTIVE: To assess whether hypoglycaemia incidence during management of adult diabetic ketoacidosis (DKA) differed following transition from a fixed-rate insulin protocol to a protocol using an empiric insulin rate reduction after normoglycaemia. METHODS: We retrospectively reviewed charts from adult patients managed with a DKA order set before and after order set revision. In cohort 1 (n = 77), insulin rate was 0.1 unit/kg/h with no adjustments and dextrose was infused at 12.5 g/h after glucose reached 250 mg/dl. In cohort 2 (n = 78), insulin was reduced to 0.05 unit/kg/h concurrent with dextrose initiation at 12.5 g/h after glucose reached 200 mg/dl. The primary outcome was hypoglycaemia (glucose < 70 mg/dl) within 24 h of the first order for insulin. KEY FINDINGS: The 24-h incidence of hypoglycaemia was 19.2% in cohort 2 versus 32.5% in cohort 1; the adjusted odds ratio was 0.46 (95% confidence interval (CI) [0.21, 0.98]; P = 0.047). The 24-h use of dextrose 50% in water (D50W) was also reduced in cohort 2. No differences were seen in anion gap or bicarbonate normalization, rebound hyperglycaemia or ICU length of stay. In most patients who became hypoglycaemic, the preceding glucose value was below 100 mg/dl. CONCLUSIONS: The insulin rate-reduction protocol was associated with less hypoglycaemia and no obvious disadvantage. Robust intervention for low-normal glucose values could plausibly achieve low hypoglycaemia rates with either approach.