Osmol gap can be used as a surrogate marker for serum propylene glycol concentration. In critically ill patients receiving lorazepam for sedation, an osmol gap above 10 was associated with concentrations previously reported to cause toxicity.

Starnes JW, Barnes BD, Olsen ME. Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca 2ϩ -induced dysfunction. J Appl Physiol 102: 1793-1798, 2007. First published February 15, 2007 doi:10.1152/japplphysiol.00849.2006.-Exercise provides cardioprotection against ischemia-reperfusion injury, a process involving mitochondrial reactive oxygen species (ROS) generation and calcium overload. This study tested the hypotheses that isolated mitochondria from hearts of endurance-trained rats have decreased ROS production and improved tolerance against Ca 2ϩ -induced dysfunction. Male Fischer 344 rats were either sedentary (Sed, n ϭ 8) or endurance exercise trained (ET, n ϭ 11) by running on a treadmill for 16 wk (5 days/wk, 60 min/day, 25 m/min, 6°grade). Mitochondrial oxidative phosphorylation measures were determined with glutamate-malate or succinate as substrates, and H2O2 production and permeability transition pore (PTP) opening were determined with succinate. All assays were carried out in the absence and presence of calcium. In response to 25 and 50 M CaCl2, Sed and ET displayed similar decreases in state 3 respiration, respiratory control ratio, and ADP:O ratio. Ca 2ϩ -induced PTP opening was also similar. However, H2O2 production by ET was lower than Sed (P Ͻ 0.05) in the absence of calcium (323 Ϯ 12 vs. 362 Ϯ 11 pmol ⅐ min Ϫ1 ⅐ mg protein Ϫ1 ) and the presence of 50 M CaCl2 (154 Ϯ 3 vs. 197 Ϯ 7 pmol ⅐ min Ϫ1 ⅐ mg protein Ϫ1 ). Rotenone, which blocks electron flow from succinate to complex 1, reduced H2O2 production and eliminated differences between ET and Sed. Mitochondrial superoxide dismutase and glutathione peroxidase were not affected by exercise. Catalase activity was extremely low but increased 49% in ET (P Ͻ 0.05). In conclusion, exercise reduces ROS production in myocardial mitochondria through adaptations specific to complex 1 but does not improve mitochondrial tolerance to calcium overload. oxidative phosphorylation; antioxidant enzymes; hydrogen peroxide; cardioprotection; ischemia-reperfusion injury REACTIVE OXYGEN SPECIES (ROS) generated by mitochondria are believed to play key roles in myocardial ischemia-reperfusion (I/R) injury (11, 27 for reviews) and myocardial dysfunction accompanying normal aging (17, 33 for reviews). During I/R, mitochondrial ROS generation can lead to general oxidative stress and calcium overload (8, 27 for reviews). The mitochondria then take up the calcium, which results in decreased ATP production and may cause the mitochondrial permeability transition pore (PTP) to open, further decreasing ATP production and releasing cytochrome c (8, 27). Age-related increases in mitochondrial oxidant production are generally accepted as a cause of myocardial cell loss via apoptosis and necrosis (28,31). It is now well accepted that exercise participation provides intrinsic protection to the heart against I/R injury (2,6,7,9,10,15,25,34,37,42) and delays age-related dysfunction and myocyte loss (31, 46). Although it has been reported that e...

Lack of standardization in antibiogram (ABGM) preparation (the overall profile of antimicrobial susceptibility results of a microbial species to a battery of antimicrobial agents) has not been addressed until recently. The objective of this study was to analyze current antibiograms using the recently published NCCLS M39-A guidelines for preparation of antibiograms to identify areas for improvement in the reporting of antibiogram susceptibility data. Antibiograms from across the United States were obtained by various methods, including direct mailings, Internet searches, and professional contacts. Each ABGM collected was analyzed using prospectively defined elements from the M39-A guidelines. Additionally, seven quality indicators were also evaluated to look for the reporting of any atypical or inappropriate susceptibility data. The 209 antibiograms collected from 149 institutions showed at least 85% compliance to 5 of the 10 M39-A elements analyzed. Clinically relevant elements not met included annual analysis, duplicate isolate notation, and the exclusion of organisms with fewer than 10 isolates. As for the quality indicators evaluated, unexpected results included the 7% of antibiograms that reported <100% vancomycin susceptibility for Staphylococcus aureus, 24% that had inconsistent betalactam susceptibility for Staphylococcus aureus, 20% that reported <100% imipenem susceptibility for Escherichia coli, and 37% that reported >0% ampicillin susceptibility for Klebsiella pneumoniae. These findings suggest that antibiograms should be reviewed thoroughly by infectious disease specialists (physicians and pharmacists), clinical microbiologists, and infection control personnel for identification of abnormal findings prior to distribution.

The objective of this review is to characterize the mechanisms, risk factors, and offending pharmacotherapeutic agents that may cause drug-induced arrhythmias in critically ill patients. PubMed, other databases, and citation review were used to identify relevant published literature. The authors independently selected studies based on relevance to the topic. Numerous drugs have the potential to cause drug-induced arrhythmias. Drugs commonly administered to critically ill patients are capable of precipitating arrhythmias and include antiarrhythmics, antianginals, antiemetics, gastrointestinal stimulants, antibacterials, narcotics, antipsychotics, inotropes, digoxin, anesthetic agents, bronchodilators, and drugs that cause electrolyte imbalances and bradyarrhythmias. Drug-induced arrhythmias are insidious but prevalent. Critically ill patients frequently experience drug-induced arrhythmias; however, enhanced appreciation for this adverse event has the potential to improve prevention, treatment, patient safety, and outcomes in this patient population.