Impaired gastrointestinal transit and its associated morbidity in the intensive care unit.

PURPOSE: To determine the proportion of critically ill adults developing impaired gastrointestinal transit (IGT) using a clinically pragmatic definition, its associated morbidity and risk factors. MATERIALS AND METHODS: Critically ill adult patients receiving enteral nutrition for ≥ 72 hours and mechanically ventilated for ≥ 48 hours were prospectively identified. IGT was defined as absence of a bowel movement for ≥ 3 days, treatment for constipation, and one of the following: (1) radiologic confirmed ileus, (2) feed intolerance, (3) abdominal distention, or (4) gastric decompression. RESULTS: One thousand patients were screened, and 248 were included for analysis. Fifty patients (20.1%; 95% confidence interval, 15.1-25.6%) developed IGT persisting for 6.5 ± 2.5 days. Patients with IGT had longer lengths of intensive care unit stay and were less likely to reach nutrition targets compared to patients without IGT or traditional definitions of constipation. Daily opioid use and pharmacological constipation prophylaxis were identified risk factors for IGT. CONCLUSION: Traditional definitions of constipation or ileus in intensive care unit patients are simplistic and lack clinical relevance. Pragmatically defined IGT is a common complication of critical illness and is associated with significant morbidity. Future interventional studies for IGT in critically ill adults should use a more clinically relevant definition and evaluate energy deficits and lengths of stay as clinically relevant outcomes.

Cardiac glycoside toxicity: more than 200 years and counting.

Digitalis toxicity produces a toxidrome characterized by gastrointestinal, neurologic, electrolyte, and nonspecific cardiac manifestations. Chronic toxicity remains much more difficult to recognize compared with an acute presentation because of the nonspecific manifestations; therefore, serum glycoside levels are essential for diagnosis in this population. The mainstay of management continues to be rapid toxidrome identification followed by digoxin-specific antibody fragment therapy with supportive care. Several controversies still remain, including therapy for patients dependent on hemodialysis, appropriateness of calcium therapy for hyperkalemia, ideal agents for arrhythmia therapy, and the potential utility of plasmapheresis for removal of bound digoxin-antibody fragment complexes.

Stability of levothyroxine injection in glass, polyvinyl chloride, and polyolefin containers.

PURPOSE: The 24-hour stability of a levothyroxine solution admixed and stored in three common infusion containers and infused through polyvinyl chloride (PVC) tubing was evaluated. METHODS: Levothyroxine sodium 1-µg/mL injection prepared in glass bottles and PVC and polyolefin bags were assayed using high-performance liquid chromatography at 0, 1, 3, 6, 12, and 24 hours; samples drawn directly from the containers, as well as from the distal end of attached PVC tubing, were assayed. The area under the time-versus-concentration curve (AUC) for predicted and delivered doses was calculated; analysis of variance was used for comparison of the percentages of predicted and actual AUC values. RESULTS: The levothyroxine concentration was stable in glass bottles and polyolefin bags through 24 hours (mean ± S.D. percentage of initial concentration remaining, 103.5% ± 2.5% and 100.0% ± 2.9%, respectively). In the PVC infusion bags, the amount of drug decreased to 90% of the initial concentration within 1 hour and then rose and remained within acceptability limits. The levothyroxine concentration of the samples infused through PVC line from glass and polyolefin containers decreased after 1 hour by about 13%; the loss of the drug from the samples infused from PVC bags was higher (18%), presumably due to additive adsorptive effects. In all samples tested, the drug concentration rebounded and remained above 90% to the end of the study. CONCLUSION: Levothyroxine sodium 1-µg/mL solution was stable for 24 hours in glass bottles and polyolefin bags but when stored in PVC bags, the concentration decreased by 10% after 1 hour.

Impact of accessory gene regulator (agr) dysfunction on vancomycin pharmacodynamics among Canadian community and health-care associated methicillin-resistant Staphylococcus aureus.

BACKGROUND: The accessory gene regulator (agr) is a quorum sensing cluster of genes which control colonization and virulence in Staphylococcus aureus. We evaluated agr function in community- (CA) and healthcare-associated (HA) MRSA, to compare the pharmacodynamics and bactericidal activity of vancomycin against agr functional and dysfunctional HA-MRSA and CA-MRSA. METHODS: 40 clinical isolates of MRSA from the Canadian Nosocomial Infection Surveillance Program were evaluated for delta-haemolysin production, as a surrogate marker of agr function. Time kill experiments were performed for vancomycin at 0 to 64 times the MIC against an initial inoculum of 10(6) and 10(8) cfu/ml of agr functional and dysfunctional CA-MRSA and HA-MRSA and these data were fit to a hill-type pharmacodynamic model. RESULTS: 15% isolates were agr dysfunctional, which was higher among HA-MRSA (26.3%) versus CA-MRSA (4.76%). Against a low initial inoculum of 10(6) cfu/ml of CA-MRSA, vancomycin pharmacodynamics were similar among agr functional and dysfunctional strains. However, against a high initial inoculum of 10(8) cfu/ml, killing activity was notably attenuated against agr dysfunctional CA-MRSA (USA400) and HA-MRSA (USA100). CA-MRSA displayed a 20.0 fold decrease in the maximal reduction in bacterial counts (Emax) which was 3.71 log(10) CFU/ml for agr functional vs. 2.41 log(10) CFU/ml for agr dysfunctional MRSA (p = 0.0007). CONCLUSIONS: Dysfunction in agr was less common among CA-MRSA vs. HA-MRSA. agr dysfunction demonstrated an impact on vancomycin bactericidal activity and pharmacodynamics against a high initial inoculum of CA-MRSA and HA-MRSA, which may have implications for optimal antimicrobial therapy against persistent, difficult to treat MRSA infections.