154 Abstracts

10, 15, and 18 h from the start of midazolam infusion.Urine was also collected and pooled at 6-h intervals duringthe study. All drug and metabolite levels were measuredwith high-performance liquid chromatography (HPLC)-tandemmass spec methods via previously validated methods. Com-pared with controls, the RYGB group had a significantly shortertime to maximum serum concentration (tmax) of all orallyadministered agents except dextromethorphan (as it could notbe measured due to low doses in both groups). The maximumserum concentration (Cmax) of orally administered caffeinewas significantly higher in the RYGB group as well, althoughit was similar for all other oral agents. CYP1A2, CYP2C9,and CYP2C19 activities were not different between the studyand control groups as assessed by drug and metabolite areaunder the curve (AUC) molar ratios. Systemic clearance andoral bioavailability of these agents also did not differ betweenthe two groups. For intravenously administered midazolam,the AUC molar ratio of midazolam metabolites to midazolamtrended toward lower than the control group, approachingstatistical significance. For the PD study, 13 RYGB subjectsand 14 age-, sex-, race-, and BMI-matched control volunteerswithout comorbidities that could affect furosemide metabolismor clearance were asked to consume a metabolic diet for 5 daysas an outpatient prior to the study until they had equilibrated inurine sodium output and daily weight for 2 days. After anovernight fast, the patients were administered 40 mg of oralfurosemide with 10 mL/kg of oral distilled water, and bloodand urine samples were collected at 0.5-, 1-, 1.5-, 2-, 2.5-, 3-,4-, 6-, 8-, and 12-h time points. Serum furosemide levels weremeasured with HPLC, and urine sodium and total urine outputswere measured to determine diuretic response with a primaryend point of total urine sodium excretion over the first 6 h, timedurine sodium excretion, and urine volume at the 0–1, 1–2, 2–4,and 4–6-h intervals. The PD study revealed that RYGBrecipients had significantly higher sodium excretion over the1–2-h time frame than controls corresponding to a significantlyshorter tmax for furosemide and higher serum drugs levelsat the 1- and 2-h time points, but without any significantdifference in urine output or oral clearance. The authorsconcluded that there was more rapid absorption of thestudied mini-cocktail agents, possibly accounted for by rapidemptying of their smaller gastric pouches into jejunum,leading to more rapid absorption. Despite this, there were nosignificant differences in bioavailability and clearance of theprobe drugs.

[Alex Badulak, MD

Denver Health Medical Center, Denver, CO]

Comments: Although there may be implications for theadministration of oral medications to RYGB patients over thelong term, this study suggests there is little difference in overallbioavailability or primary PK and PD end points for commonmedications and metabolic pathways in this patient population.As we often administer medications intravenously in theemergency department for acute problems, this study has littlebearing on how to approach the critically ill RYGB patientexcept in the case of intravenous midazolam, which may requireinitial higher doses for adequate duration of sedation in these

patients given the more rapid hepatic metabolism observed inthis study.

, CAUSE OF DEATH WITHIN 30 DAYS OF PERCU-TANEOUS CORONARY INTERVENTION IN AN ERAOFMANDATORYOUTCOMEREPORTING.Bhuvnesh A,Ellis SG, Lincoff AM, et al. JAm Coll Cardiol 2013;62:409–15.

In anticipation of public reporting of outcomes afterpercutaneous coronary intervention (PCI) becoming standardpractice, this study from a single tertiary care center sought toinvestigate the incidence and causes of death in patients whohad undergone PCI. Death within 30 days post interventionwas studied through a retrospective chart review of a PCIregistry examining cardiac, noncardiac, PCI- and non-PCI-related causes of death from January 2009 to April 2011.Cardiac death was defined as myocardial infarction, low outputfailure, fatal dysrhythmia, unwitnessed death, death fromunknown cause, procedure-related deaths, and all deaththat could not show clear noncardiac cause. Noncardiaccauses were divided into respiratory, infectious, neurological,gastrointestinal, renal, and hemato-oncological categories.PCI-related death was defined as death from complication ofprocedure such as vascular dissection, aneurysm, perforation,bleeding, renal failure, and definite or probable stent throm-bosis. From a total of 4078 PCIs performed, all-cause mortalitywas 2% (n = 81). Of those, 58% (n = 47) died from cardiac and42% (n = 34) died from noncardiac causes. Of the cardiacdeaths, 72% (n = 34) of patients died from PCI-relatedcomplications. Predictors for non-PCI-related death werepatients who presented with cardiogenic shock (p < 0.01) orcardiac arrest (p < 0.01) prior to hospitalization. Whencompared to chart review, analysis of death certificates showedonly a 58% accuracy (95% confidence interval 45–72%) forclassifying patients as cardiac vs. noncardiac death.

[Java Tunson, MD

Denver Health Medical Center, Denver, CO]

Comments: The main limitation of this study is its retrospec-tive design that the authors readily concede led to questionableresults. Because the authors themselves noted that only 58% ofdeath certificates accurately record the true cause of death, thenthe results of this study are impossible to interpret. Still, thequestion being asked is important given the mandatory reportingrequirement for this procedure. Clearly, to better define thecurrent state, a prospective study needs to be done.

, OUTCOMES OF MORBIDLY OBESE PATIENTSRECEIVING INVASIVEMECHANICALVENTILATION:A NATIONWIDE ANALYSIS. Kumar G, Majumdar T,Jacobs E, et al. Chest 2013;144:48–54.

Previous studies have shown contradictory results regardingthe effects of obesity in the critically ill. Limited data havesuggested that obesity increases the risk of prolongedmechanical ventilation and acute respiratory distress syndrome,but may also have protective effects. This retrospective cohortstudy aimed to determine if outcomes varied in morbidly obesepatients compared to nonobese patients receiving invasivemechanical ventilation (IMV). The population included patients