Development and simultaneous application of multiple care protocols in critical care: a multicenter feasibility study

OBJECTIVE: To test the feasibility of and interactions among three software-driven critical care protocols. DESIGN: Prospective cohort study. SETTING: Intensive care units in six European and American university hospitals. PATIENTS: 174 cardiac surgery and 41 septic patients. INTERVENTIONS: Application of software-driven protocols for cardiovascular management, sedation, and weaning during the first 7 days of intensive care. MEASUREMENTS AND RESULTS: All protocols were used simultaneously in 85% of the cardiac surgery and 44% of the septic patients, and any one of the protocols was used for 73 and 44% of study duration, respectively. Protocol use was discontinued in 12% of patients by the treating clinician and in 6% for technical/administrative reasons. The number of protocol steps per unit of time was similar in the two diagnostic groups (n.s. for all protocols). Initial hemodynamic stability (a protocol target) was achieved in 26+/-18 min (mean+/-SD) in cardiac surgery and in 24+/-18 min in septic patients. Sedation targets were reached in 2.4+/-0.2h in cardiac surgery and in 3.6 +/-0.2h in septic patients. Weaning protocol was started in 164 (94%; 154 extubated) cardiac surgery and in 25 (60%; 9 extubated) septic patients. The median (interquartile range) time from starting weaning to extubation (a protocol target) was 89 min (range 44-154 min) for the cardiac surgery patients and 96 min (range 56-205 min) for the septic patients. CONCLUSIONS: Multiple software-driven treatment protocols can be simultaneously applied with high acceptance and rapid achievement of primary treatment goals. Time to reach these primary goals may provide a performance indicator

Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action

Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or “golden rules,” for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice

Characterization of Dibenzo[a,l ]pyrene-trans-11,12-diol (Dibenzo[def,p]chrysene) Glucuronidation by UDP-glucuronosyltransferases

Dibenzo[ a,l ]pyrene (DB[ a,l ]P) (dibenzo[ def,p ]chrysene) is a highly carcinogenic polycyclic aromatic hydrocarbon (PAH) that has been identified in tobacco smoke and is found in our environment due to incomplete combustion of organic matter. Its metabolites are known to form stable DNA adducts in bacteria and mammalian cells, and can lead to tumors in animal models. Glucuronidation of major metabolites of DB[ a,l ]P by the uridine-5’-diphosphate glucuronosyltransferase (UGT) family of enzymes is an important route of detoxification of this pro-carcinogen. The focus of the current study was to characterize the glucuronidation of the pro-carcinogenic enantiomers DB[ a,l ]P-(+)- trans -11 S ,12 S –diol and DB[ a,l ]P-(−)- trans -11 R ,12 R –diol. Glucuronidation assays with HEK293 cell lines over-expressing individual human UGT enzymes demonstrated that UGTs 1A1, 1A4, 1A7, 1A8, 1A9, 1A10, and 2B7 glucuronidated one or both DB[ a,l ]P- trans -11,12-diol enantiomers. Three glucuronide conjugates were observed in activity assays with UGTs 1A1 and 1A10, while two glucuronides were formed by UGTs 1A7, 1A8, and 1A9, and one glucuronide was made by UGT1A4 and UGT2B7. Enzyme kinetic analysis indicated that UGT1A9 was the most efficient UGT at forming both the (+)-DB[ a,l ]P-11-Gluc and (−)-DB[ a,l ]P-11-Gluc products while UGTs 1A1 and 1A10 were the most efficient at forming the (+)-DB[ a,l ]P-12-Gluc product (as determined by the k cat / K M ). Incubations with human liver microsomes showed formation of three diastereomeric glucuronide products: (+)-DB[ a,l ]P-11-Gluc, (+)-DB[ a,l ]P-12-Gluc, and (−)-DB[ a,l ]P-11-Gluc, with an average overall ratio of 31 : 32 : 37 in four liver specimens. Human bronchus and trachea tissue homogenates demonstrated glucuronidation activity against both DB[ a,l ]P- trans -11,12-diol enantiomers, with both tissues producing the (+)-DB[ a,l ]P-11-Gluc and (+)-DB[ a,l ]P-12-Gluc with little or no formation of (−)-DB[ a,l ]P-11-Gluc. These results indicate that multiple UGTs are involved in the stereospecific glucuronidation of DB[ a,l ]P- trans -11,12-diol in a pattern consistent with their expression in respiratory tract tissues, and that glucuronidation may be an important first-line detoxification mechanism of DB[ a,l ]P metabolites