High target attainment for ß-lactam antibiotics in intensive care unit patients when actual minimum inhibitory concentrations are applied.

Patients in the intensive care unit (ICU) are at risk for suboptimal levels of ß-lactam antibiotics, possibly leading to poor efficacy. Our aim was to investigate whether the actual minimum inhibitory concentration (MIC) compared to the more commonly used arbitrary epidemiological cut-off values (ECOFFs) would affect target attainment in ICU patients on empirical treatment with broad-spectrum ß-lactam antibiotics and to identify risk factors for not reaching target. In a prospective, multicenter study, ICU patients ≥18 years old and treated with piperacillin/tazobactam, meropenem, or cefotaxime were included. Clinical and laboratory data were recorded. Serum trough antibiotic levels from three consecutive days were analyzed by liquid chromatography-mass spectrometry (LC-MS). The target was defined as the free trough concentration above the MIC (100% fT>MIC). MICECOFF was used as the target and, when available, the actual MIC (MICACTUAL) was applied. The median age of the patients was 70 years old, 52% (58/111) were males, and the median estimated glomerular filtration rate (eGFR) was 48.0 mL/min/1.73 m2. The rate of patients reaching 100% fT > MICACTUAL was higher (89%, 31/35) compared to the same patients using MICECOFF (60%, p = 0.002). In total, 55% (61/111) reached 100% fT > MICECOFF. Increased renal clearance was independently associated to not reaching 100% fT > MICECOFF. On repeated sampling, >77% of patients had stable serum drug levels around the MICECOFF. Serum concentrations of ß-lactam antibiotics vary extensively between ICU patients. The rate of patients not reaching target was markedly lower for the actual MIC than when the arbitrary MIC based on the ECOFF was used, which is important to consider in future studies.

Bispectral index monitoring: appreciated but does not affect drug dosing and hypnotic levels.

BACKGROUND: Bispectral index (BIS) has been associated with benefits from less-deep anesthesia as well as preventing awareness, albeit not at the same time. We investigated how increasing experience from BIS in clinical practice affect the hypnotic level, drug consumption, as well as subjective opinions on this monitoring. METHODS: Eight certified registered nurse anesthetists (CRNAs) with previous experience from 88 (46-121) BIS monitored cases anesthetized 80 cases with concealed BIS, followed by 80 cases with available BIS. Additional education and training was followed by yet another 160 patients randomized to open or blindly recorded BIS. BIS levels, anesthetic gas consumption, fentanyl use, and subjective opinions on utility and reliability were investigated. RESULTS: After gaining initial experience from BIS monitoring, the fraction of time with BIS levels of 40-60 did not deteriorate in cases with concealed monitoring and no further improvement was found in subsequent cases with available data from the BIS monitoring, not even after additional training and encouragement to adhere to the 40-60 interval. Compared with the first experience from BIS monitoring the subjective opinions on utility had increased from 33 to 78 mm (100 mm visual analog scales) (P<0.0001). CONCLUSION: Although BIS became considerably appreciated, growing experience and repeated education had no impact on drug dosing and BIS levels.

Reduction in the incidence of awareness using BIS monitoring.

BACKGROUND: Explicit recall (ER) is evident in approximately 0.2% of patients given general anaesthesia including muscle relaxants. This prospective study was performed to evaluate if cerebral monitoring using BIS to guide the conduction of anaesthesia could reduce this incidence significantly. PATIENTS AND METHODS: A prospective cohort of 4945 consecutive surgical patients requiring muscle relaxants and/or intubation were monitored with BIS and subsequently interviewed for ER on three occasions. BIS values between 40 and 60 were recommended. The results from the BIS-monitored group of patients was compared with a historical group of 7826 similar cases in a previous study when no cerebral monitoring was used. RESULTS: Two patients in the BIS-monitored group, 0.04%, had ER as compared with 0.18% in the control group (P < 0.038). Both BIS-monitored patients with ER were aware during intubation when they had high BIS values (> 60) for 4 min and more than 10 min, respectively. However, periods with high BIS = 4 min were also evident in other patients with no ER. Episodes with high BIS, 4 min or more, were found in 19% of the monitored patients during induction, and in 8% of cases during maintenance. CONCLUSIONS: The use of BIS monitoring during general anaesthesia requiring endotracheal intubation and/or muscle relaxants was associated with a significantly reduced incidence of awareness as compared with a historical control population.

Expression of the human transferrin receptor in subrenal capsule assay in the mouse.

The expression of a cell proliferation marker, the human transferrin receptor, was studied in ten human gastrointestinal tumors prior to and after implantation under the renal capsule in the mouse (1-6 days). These data were compared to the increase in tumor size in situ, and to the infiltration of inflammatory cells. All tumors studied expressed the transferrin receptor prior to implantation. Forty of 47 implants expressed the receptor, the strongest expression occurring on day 4, accompanied by a reorganization of tumor tissue to a morphology similar to that before implantation. On days 5 and 6 the expression of the transferrin receptor declined. Implants showed maximal increase in size on days 1 and 2, decreased in size on days 3 and 4, and increased again on days 5 and 6. The increase in the size of the implants on days 5 and 6 was accompanied by considerable infiltration of inflammatory cells, and was probably mostly a result of invading host cells and inflammation. If size alone is used as a criterion for tumor proliferation in this subrenal capsule assay, day 4 seems to be the most appropriate for evaluation. This is supported by a strong expression of a proliferation marker, the human transferrin receptor, during this time.