Wash-in Period Research Articles

The Physiological and Clinical Effects of Interrupting a Treatment Regimen of Hydroxyurea in Young Children with Sickle Cell Anemia (SCA)

Abstract▪2134▪This icon denotes a clinically relevant abstractBABY HUG randomly assigned children with sickle cell anemia ages 9 to 18 months at entry to a two-year double-masked treatment course of 20 mg/kg/d of hydroxyurea (HU) or placebo (PBO). The primary goal of this clinical trial was to determine if treatment with HU could reduce organ damage or dysfunction (spleen function assessed by 99mTc-sulfur colloid and renal function by 99mTc-DTPA clearance) by 50%. Children were seen at least monthly for blood and clinical evaluations. [Lancet 2011; 377(9778):1663–1672.]Between March 23, 2006 and June 1, 2006, the BABY HUG study was placed on “clinical hold” due to the omission of an expiration date on the treatment label for one lot of the study treatments. During the clinical hold, there were 94 children on active study treatment (47 HU, 47 PBO); four and six children, respectively, had finished their two-year follow up. Subjects continued regular visits and clinical event monitoring but received no study medication. To examine the impact of the clinical hold on toxicity and clinical events, the BABY HUG study period was divided into three intervals: Before, During, and After the clinical hold. Each period was offset by a one-month delay from the actual onset and end date to allow for wash-out and wash-in periods surrounding the clinical hold. The clinical hold produced both hold effects (effects produced by the hold that were consistent in the two treatment groups) and treatment-hold interaction effects (hold effects that were different by treatment). The interaction effects are presented below.The table presents the rate or prevalence of selected clinical events during each interval. The rate of pain, one of the clinical events shown to benefit from treatment with HU, was comparable to the PBO rate during the clinical hold but was significantly lower in the pre- and post-hold intervals. The prevalence of splenomegaly (defined by palpation ≥2 cm below the costal margin), which was slightly greater in the HU group than in the PBO group during the pre- and post-hold intervals, increased to a four-fold difference during the clinical hold. There was no difference between the groups in the rate of splenic sequestration in any interval.Clinical Events Before, During and After Clinical Hold+Before HoldDuring HoldAfter HoldHU 55.1*PBO 50.3*HU 8.3*PBO 7.8*HU 125.1*PBO 126.8*AENo.RateNo.RateNo.RateNo.RateNo.RateNo.RateDactylitis59.13467.6112.0338.51814.48667.8Pain3461.772143.114168.715192.3129103.1288227.1Splenomegaly^3054.42039.814168.7338.58366.36551.6Lab ResultsMeanMeanMeanMeanMeanMeanRetic Ct (k/mm3)191.5329.4300.5327.3237.0335.4Hgb (gm/dL)10.078.699.098.739.288.69MCV (fL)86.8481.9082.8279.8585.0080.00+Rates in bold are significantly different at p < 0.05 within each time period*Person Years of Exposure^PrevalenceHematologic changes showing a treatment-period interaction included a significantly larger difference in absolute reticulocyte count between the HU and placebo group During the Hold as compared to Before and After. The HU-induced increase in Hb and MCV was significantly diminished During the Hold. All measurements moved back towards their pre-hold differences after the hold was lifted.The clinical hold in BABY HUG provided an unforeseen opportunity to study the clinical and laboratory impact of cessation of HU therapy for a brief time period. No serious clinical effects or toxicities occurred during the clinical hold, perhaps due to its limited time span. Parents and physicians should be aware that stopping HU therapy may result in increased episodes of pain or splenic enlargement. Disclosures:Off Label Use: Hydroxyurea which is not approved for use in children with sickle cell disease. Casella:Adventrix: Honoraria.

Mathematical method to build an empirical model for inhaled anesthetic agent wash-in

BackgroundThe wide range of fresh gas flow - vaporizer setting (FGF - FD) combinations used by different anesthesiologists during the wash-in period of inhaled anesthetics indicates that the selection of FGF and FD is based on habit and personal experience. An empirical model could rationalize FGF - FD selection during wash-in.MethodsDuring model derivation, 50 ASA PS I-II patients received desflurane in O2 with an ADU® anesthesia machine with a random combination of a fixed FGF - FD setting. The resulting course of the end-expired desflurane concentration (FA) was modeled with Excel Solver, with patient age, height, and weight as covariates; NONMEM was used to check for parsimony. The resulting equation was solved for FD, and prospectively tested by having the formula calculate FD to be used by the anesthesiologist after randomly selecting a FGF, a target FA (FAt), and a specified time interval (1 - 5 min) after turning on the vaporizer after which FAt had to be reached. The following targets were tested: desflurane FAt 3.5% after 3.5 min (n = 40), 5% after 5 min (n = 37), and 6% after 4.5 min (n = 37).ResultsSolving the equation derived during model development for FD yields FD=-(e(-FGF*-0.23+FGF*0.24)*(e(FGF*-0.23)*FAt*Ht*0.1-e(FGF*-0.23)*FGF*2.55+40.46-e(FGF*-0.23)*40.46+e(FGF*-0.23+Time/-4.08)*40.46-e(Time/-4.08)*40.46))/((-1+e(FGF*0.24))*(-1+e(Time/-4.08))*39.29). Only height (Ht) could be withheld as a significant covariate. Median performance error and median absolute performance error were -2.9 and 7.0% in the 3.5% after 3.5 min group, -3.4 and 11.4% in the 5% after 5 min group, and -16.2 and 16.2% in the 6% after 4.5 min groups, respectively.ConclusionsAn empirical model can be used to predict the FGF - FD combinations that attain a target end-expired anesthetic agent concentration with clinically acceptable accuracy within the first 5 min of the start of administration. The sequences are easily calculated in an Excel file and simple to use (one fixed FGF - FD setting), and will minimize agent consumption and reduce pollution by allowing to determine the lowest possible FGF that can be used. Different anesthesia machines will likely have different equations for different agents.

Pinto beans as part of a normal diet do not improve glycemic control in adults with type 2 diabetes

This study examined the impact of daily consumption of ½ c pinto beans, compared to a control (½ c green beans), on changes in fasting glucose, postprandial glucose and HbA1c concentrations in men and women with type 2 diabetes (controlled by diet or metformin). Although some health professionals are promoting the benefits of dry beans for glucose control, confusion exists regarding the glycemic properties of dry beans in the context of a normal diet. After a baseline wash‐in period, 16 subjects were randomly assigned to 2 treatment periods [control period and pinto beans], each 12‐weeks in duration with a 4‐week wash‐out period. Eight subjects completed both treatment periods. During the wash‐in period and interventions, on days a diet record was kept (28 total days), subjects measured a postprandial capillary glucose concentration using a glucometer (provided by study) 1 hour after the meal during which the pinto beans or control were consumed. Before and after each intervention, subjects provided a fasted venous blood sample for glucose and HbA1c analyses. There were no statistically significant changes (p&lt;0.05) in fasting glucose, HbA1c or average postprandial glucose values between the 2 interventions. The results of this study did not demonstrate improved glycemic control when pinto beans were incorporated into the normal diet of men and women with type 2 diabetes.Research was supported by the US Dry Bean Council.

Chronic Obstructive Pulmonary Disease: Quantitative and Visual Ventilation Pattern Analysis at Xenon Ventilation CT Performed by Using a Dual-Energy Technique

To evaluate the potential of xenon ventilation computed tomography (CT) in the quantitative and visual analysis of chronic obstructive pulmonary disease (COPD). This study was approved by the institutional review board. After informed consent was obtained, 32 patients with COPD underwent CT performed before the administration of xenon, two-phase xenon ventilation CT with wash-in (WI) and wash-out (WO) periods, and pulmonary function testing (PFT). For quantitative analysis, results of PFT were compared with attenuation parameters from prexenon images and xenon parameters from xenon-enhanced images in the following three areas at each phase: whole lung, lung with normal attenuation, and low-attenuating lung (LAL). For visual analysis, ventilation patterns were categorized according to the pattern of xenon attenuation in the area of structural abnormalities compared with that in the normal-looking background on a per-lobe basis: pattern A consisted of isoattenuation or high attenuation in the WI period and isoattenuation in the WO period; pattern B, isoattenuation or high attenuation in the WI period and high attenuation in the WO period; pattern C, low attenuation in both the WI and WO periods; and pattern D, low attenuation in the WI period and isoattenuation or high attenuation in the WO period. Among various attenuation and xenon parameters, xenon parameters of the LAL in the WO period showed the best inverse correlation with results of PFT (P < .0001). At visual analysis, while emphysema (which affected 99 lobes) commonly showed pattern A or B, airway diseases such as obstructive bronchiolitis (n = 5) and bronchiectasis (n = 2) and areas with a mucus plug (n = 1) or centrilobular nodules (n = 5) showed pattern D or C. WI and WO xenon ventilation CT is feasible for the simultaneous regional evaluation of structural and ventilation abnormalities both quantitatively and qualitatively in patients with COPD.

Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs

The present study focused on the hypothesis that dietary supplementation with medium-chain TAG (MCT) will improve cognitive function in aged dogs by providing the brain with energy in the form of ketones. Aged Beagle dogs were subjected to a baseline battery of cognitive tests, which were used to establish cognitively equivalent control or treatment groups. The dogs in the treatment group were maintained on a diet supplemented with 5.5 % MCT. After an initial wash-in period, all the dogs were tested with a battery of cognitive test protocols, which assessed sequentially landmark discrimination learning ability, egocentric visuospatial function and attention. The groups were maintained on the diets for 8 months. The MCT-supplemented group showed significantly better performance in most of the test protocols than the control group. The group differences also varied as a function of task difficulty, with the more difficult task showing greater supplementation effects than the easier tasks. The group given the MCT supplement showed significantly elevated levels of beta-hydroxybutyrate, a ketone body. These results indicate, first, that long-term supplementation with MCT can have cognition-improving effects, and second, that MCT supplementation increases circulating levels of ketones. The results support the hypothesis that brain function of aged dogs can be improved by MCT supplementation, which provides the brain with an alternative energy source.

Risedronate clinical efficacy and bisphosphonate new effectiveness data from real world clinical practice

Introduction Women with accelerated bone loss are at an increased risk of fracture at any time, at any site across the skeleton. Once the first fracture occurs, the risk for further fractures increases dramatically, with one in four women at risk for another vertebral fracture within one year following their first vertebral fracture. Consequently, these high-risk patients require prompt treatment. Efficacy onset is an important marker in treatment efficacy; risedronate was shown to significantly reduce clinical vertebral fracture and osteoporosis-related non-vertebral fractures incidence within six months of treatment initiation. Forms of secondary osteoporosis include glucocorticoid-induced osteoporosis (GIO) which may be considered the most predictable and debilitating complication of glucocorticoid therapy and can cause fractures after minimal trauma. Glucocorticosteroids (GC) primarily affect trabecular bone and ultimately lead to fractures in 30–50% of patients. In addition, this increase in the risk of fracture occurs shortly after treatment initiation. Among bisphosphonates effective in this secondary osteoporosis, risedronate was shown in a combined post-hoc analysis of 2 one-year clinical studies in 518 patients (men and women) either initiating or continuing long term GC therapy, to significantly reduce the risk of fracture (RRR 70%). Method In post-menopausal women, the efficacy of risedronate, as demonstrated in Randomized Clinical Trials, is confirmed by new findings in real life clinical practice. The REAL study is a retrospective cohort study that investigated the incidence of hip and nonvertebral fractures in patients, one year after initiation of once-weekly risedronate or alendronate. 9% of the population was under GC. Significant differences in fracture incidence were seen at both 6 and 12 months following treatment initiation with a more rapid decrease in hip and nonvertebral fracture incidence with risedronate compared to alendronate. Due to the commercialization of new molecules, increasing differences of patients profile were observed depending of their respective osteoporosis treatment. Therefore, to evaluate treatment effects on fracture risk reduction in real life, a new study methodology was developed by comparing, within each treatment group, the fracture incidence in the first three months with that in the subsequent year. This new methodology aims to assess the effectiveness of therapies within their actual population, although limiting prescription bias. Results The results showed that, relative to the 3-month wash-in period, the following 12-month treatment period reduced the occurrence of clinical fractures, especially vertebral, nonvertebral and hip fractures, by 57%, 28% and 18% for alendronate, and 54%, 22% and 28% for risedronate, respectively, whereas with ibandronate, a decrease was observed only for clinical vertebral fractures, but not for nonvertebral or hip fractures. Conclusions These results are consistent with the efficacy data from the randomised, placebo-controlled clinical trials of these drugs.

Altered NDRG1 expression in breast cell lines influences apoptosis

Our objective was to detect variations of ovarian vascularization that occur in the estrus cycle of the ewe using an IV contrast agent. Five ewes were investigated using contrast-enhanced power Doppler after Sonovue® injection at day 0, 3, 5, 10 and 13 of the cycle in two successive estrus cycles. Transvaginal ultrasound monitoring of each ewe was performed after a dose of Sonovue®. Parameters derived from the time-intensity curves were compared. Quantification of the enhancement and wash-in period parameters changed significantly between ovaries and between the follicular and luteal periods of the cycle. Uptake time, wash-out time, total time of enhancement and area under the curve were the parameters with the smallest variation between ovaries. Wash-out time and area under the curve are two contrast parameters that did not change with cyclic changes. Thus, using these parameters in premenopausal women will allow more accurate detection of vascular modifications that may be associated with ovarian cancer. (E-mail: [email protected])

Double-Blind, Randomized Trial of Dexmethylphenidate Hydrochloride for the Treatment of Sarcoidosis-Associated Fatigue

Fatigue is a common complaint in patients with sarcoidosis. We studied the effectiveness of dexmethylphenidate hydrochloride (d-MPH) in treating sarcoidosis-associated fatigue. This was a double-blind, randomized, placebo-controlled, crossover trial of d-MPH. Patients were seen weekly and completed Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Fatigue Assessment Score (FAS) instruments. After a 1-week wash-in period, patients received either d-MPH or placebo. After 8 weeks, the medications were stopped. Following a 2-week wash-out period, patients were crossed over to 8 weeks of the other treatment. FVC and 6-min walk distance (6MWD) were determined initially and after each treatment arm. Ten patients with sarcoidosis were enrolled: 8 women and 5 African Americans. All were receiving systemic sarcoidosis therapy. Significant improvement in fatigue was reported by patients when receiving d-MPH (FACIT-F, p < 0.001; FAS, p < 0.02). FVC was higher at the end of 8 weeks of d-MPH compared to the baseline values (baseline median, 2.38 L; range, 1.17 to 4.53 L; placebo median, 2.41 L; range, 1.50 to 4.65 L; d-MPH median, 2.56 L; range, 1.50 to 4.96 L; p < 0.01). There was no significant difference in the 6MWD (baseline median, 330 m; range, 60 to 460 m; placebo median, 350 m; range, 180 to 460 m; d-MPH median, 390 m; range, 200 to 460 m). d-MPH was well tolerated. Treatment with d-MPH was associated with a significant improvement in sarcoidosis-associated fatigue. Clinicaltrials.gov Identifier: NCT00361387.

Magnetic Resonance Imaging and Late-Life Depression: Potential Biomarkers in the Era of Personalized Medicine

Magnetic Resonance Imaging and Late-Life Depression: Potential Biomarkers in the Era of Personalized Medicine

Can Emergency Medical Dispatch Systems Safely Reduce First-Responder Call Volume?

Objectives. Emergency medical dispatch (EMD) protocols are intended to match response resources with patient needs. In a small city that previously sent a first-responder basic life support (BLS) engine company lights-and-siren response to every emergency medical services (EMS) call, regardless of nature or severity, an EMD system was implemented in order to reduce the number of such responses. The study objectives were to determine the effects of the EMD system on first-responder call volume andto assess the safety of the system. Methods. This was a prospective, before–after trial. Using computer-assisted dispatch (CAD) records, all EMS calls in the 120 days before implementation of the EMD protocol andthe 120 days after implementation were identified (excluding a one-month wash-in period). In the “after” phase, patient care reports of a random sample of cases in which an ambulance was dispatched with no first responders was manually reviewed to assess whether there might have been any benefit to first-responder dispatch. Given the lack of accepted clinical criteria for need for first responders, the investigators' clinical judgment was used. Paired t-tests were used to compare groups. Results. There were 9,820 EMS calls in the “before” phase, with 8,278 first-responder engine runs (84.3%), and9,943 EMS calls in the “after” phase, with 3,804 first-responder engine runs (39.1%). The first-responder companies were dispatched to a median of 5.65 runs/day (range 1.1–12.7) in the “before” phase, and3.17 runs/day (range 0.6–5.0) in the “after” phase (p = 0.0008 by paired t-test). Review of 1,816 “after” phase ambulance-only patient care reports (PCRs) found ten (0.55%) in which first-responder dispatch might have been beneficial, but review of EMS andemergency department (ED) records found no adverse outcomes in these ten patients. Conclusions. This study suggests that a formal EMD system can reduce first-responder call volume by roughly one-half. The system appears to be safe for patients, with an undertriage rate of about one-half of one percent.

Dose Reponse Effects Of Caffeine During Exercise In Young Children

Only three studies have systematically investigated the effects of caffeine in children during exercise (Barta, Acta Paediatr.,1982; Turley, Med. Sci. Sports Exerc., 2005; Turley, Ped. Exerc. Sci., 2006) and all used relatively high doses of caffeine (4-5mg/ kg). No study has investigated the physiological dose response effects of caffeine in children during submaximal exercise. PURPOSE: Determine the influence of low (1mg/kg), moderate (3mg/kg), and high (5mg/kg) doses of caffeine on physiological responses to exercise in young children. METHODS: Forty children (20 boys and 20 girls) ages 7–9 years participated in a randomized, double-blind, counter-balanced, cross-over study. Over four separate visits each child consumed a placebo (PL-cherry flavored drink), 1.0 mg/kg (CAF-1), 3.0 mg/kg (CAF-3), and 5 mg/kg (CAF-5) of anhydrous caffeine mixed with PL, and then rested. After an hour wash-in period, resting measurements were taken (heart rate (HR) and blood pressure (BP)) and the children then rode at 25 W and 60% VO2max for eight minutes each. During exercise HR, VO2, and respiratory exchange ratio (RER) were measured continuously and BP was measured every two minutes. RESULTS: Resting HR was significantly (p<0.05) lower at 3 and 5 mg/kg vs PL (79.9±9.1 and79.0±6.8vs 84.8±10.4, respectively). HR was significantly lower in CAF-3 and CAF-5 vs PL at 25W (122.8±12.2 and 122.0±10.9 vs 128.4±12. respectively) and 60% VO2max (153.5±13.4 and 154.0±15.0 vs 158.9±13.9, respectively). Resting diastolic BP (DBP) was significantly higher in CAF-1, CAF-3, and CAF-5 vs PL (65.2±6.6, 66. 0±5.9, 66.6±7.8 vs 61.3±7.0, respectively). Resting systolic BP (SBP) was significantly higher at CAF-5 vs and PL (109.7±8.7 vs 104.9±9.0 respectively). RER, at 60% VO2max was significantly higher in CAF-5 vs andPL(1.02±0.04vs 1.00±0.04, respectively) CONCLUSIONS: In this study low, moderate, and high doses of caffeine were found to significantly increase DBP at rest. During rest and exercise, moderate and high doses of caffeine significantly lowered HR. Although there was a trend for CAF-5 to elevate BP during exercise, it was not significant.

Do distribution volumes and clearances relate to tissue volumes and blood flows? A computer simulation

BackgroundKinetics of inhaled agents are often described by physiological models. However, many pharmacokinetic concepts, such as context-sensitive half-times, have been developed for drugs described by classical compartmental models. We derived classical compartmental models that describe the course of the alveolar concentrations (FA) generated by the physiological uptake and distribution models used by the Gas Man® program, and describe how distribution volumes and clearances relate to tissue volumes and blood flows.MethodsGas Man® was used to generate FA vs. time curves during the wash-in and wash-out period of 115 min each with a high fresh gas flow (8 L.min-1), a constant alveolar minute ventilation (4 L.min-1), and a constant inspired concentration (FI) of halothane (0.75%), isoflurane (1.15%), sevoflurane (2%), or desflurane (6%). With each of these FI, simulations were ran for a 70 kg patient with 5 different cardiac outputs (CO) (2, 3, 5, 8 and 10 L.min-1) and for 5 patients with different weights (40, 55, 70, 85, and 100 kg) but the same CO (5 L.min-1). Two and three compartmental models were fitted to FA of the individual 9 runs using NONMEM. After testing for parsimony, goodness of fit was evaluated using median prediction error (MDPE) and median absolute prediction error (MDAPE). The model was tested prospectively for a virtual 62 kg patient with a cardiac output of 4.5 L.min-1 for three different durations (wash-in and wash-out period of 10, 60, and 180 min each) with an FI of 1.5% halothane, 1.5% isoflurane, sevoflurane 4%, or desflurane 12%.ResultsA three-compartment model fitted the data best (MDPE = 0% and MDAPE ≤ 0.074%) and performed equally well when tested prospectively (MDPE ≤ 0.51% and MDAPE ≤ 1.51%). The relationship between CO and body weight and the distribution volumes and clearances is complex.ConclusionThe kinetics of anesthetic gases can be adequately described e by a mammilary compartmental model. Therefore, concepts that are traditionally thought of as being applicable to the kinetics of intravenous agents can be equally well applied to anesthetic gases. Distribution volumes and clearances cannot be equated to tissue volumes and blood flows respectively.

Effects of Caffeine on Physiological Responses to Exercise in Young Boys and Girls

To describe the influence of caffeine on physiological responses to exercise in young children and determine whether sex differences in these responses exist. Twenty-six healthy 7- to 9-yr-old boys and 26 healthy 7- to 9-yr-old girls volunteered to participate in a double-blind, randomized, double crossover study design. Each child randomly received both the placebo (PL) and caffeinated (5 mg x kg(-1)) drink (CAF) twice each on four separate days. Following a 1-h wash-in period and resting measures, each child rode a cycle ergometer at 25 and then 50 W for 8 min each, while HR, blood pressure (BP), and oxygen consumption (VO2) were measured. HR (bpm) was significantly (P < 0.05) lower at rest and at 25 and 50 W in CAF versus PL in both boys and girls. Diastolic BP (mm Hg) was significantly (P </= 0.05) higher at rest, 25 W in both boys and girls, and at 50 W in boys, in CAF versus PL. Systolic BP (mm Hg) was significantly (P </= 0.05) higher at rest in both boys and girls, at 25 W in boys, and at 50 W in girls. During exercise, VO2 (L x min(-1) or mL x kg(-1) x min(-1)) and RER were not different in CAF versus PL in either boys or girls. A moderate dose of caffeine (5 mg.kg) does not affect metabolism (VO2 or RER) in young children at low-moderate intensities of exercise. However, CAF causes a significantly lower HR (bpm) and higher BP (mm Hg) in both young boys and girls.

Assessment of cyclic changes of microvessels in ovine ovaries using sonovue® contrast-enhanced ultrasound

Our objective was to detect variations of ovarian vascularization that occur in the estrus cycle of the ewe using an IV contrast agent. Five ewes were investigated using contrast-enhanced power Doppler after Sonovue® injection at day 0, 3, 5, 10 and 13 of the cycle in two successive estrus cycles. Transvaginal ultrasound monitoring of each ewe was performed after a dose of Sonovue®. Parameters derived from the time-intensity curves were compared. Quantification of the enhancement and wash-in period parameters changed significantly between ovaries and between the follicular and luteal periods of the cycle. Uptake time, wash-out time, total time of enhancement and area under the curve were the parameters with the smallest variation between ovaries. Wash-out time and area under the curve are two contrast parameters that did not change with cyclic changes. Thus, using these parameters in premenopausal women will allow more accurate detection of vascular modifications that may be associated with ovarian cancer. (E-mail: marret@med.univ-tours.fr)

Combined general‐epidural anesthesia decreases the desflurane requirement for equivalent A‐line ARX index in colorectal surgery

The present study used the A-line ARX index, derived from auditory evoked potential measurements, to examine the effect of epidural lidocaine on the end-tidal concentration of desflurane during general anesthesia. Thirty ASA I-II patients scheduled for elective colorectal surgery were included and randomized, in a double-blinded fashion, to receive general anesthesia, and 15 ml of either 2% lidocaine (group GE, n=15) or normal saline (group GS, n=15) was administered epidurally with a maintenance infusion rate of 6 ml h-1. After a 10-min high-flow oxygen wash-in period, desflurane was titrated to a target A-line ARX index (AAI) of 20+/-5. Epidural lidocaine reduced the end-tidal concentration of desflurane required to maintain an adequate clinical effect by 42% compared to general anesthesia alone (2.6% vs. 4.5%, respectively; P<0.001). The initial mean value of AAI was 87.8 (range 78-99) in group GE and 88.13 (79-99) in group GS before general anesthesia induction, the AAI values were approximately 19.7 (15-25) in group GE and 20.2 (16-25) in group GS during anesthesia maintenance, and returned to 84.53 (77-98) in group GE and 86.87 (79-98) in group GS when the patients regained consciousness in the recovery room. No statistical difference in the AAI values was observed either before, during, or after emergence of anesthesia. No patient reported intraoperative awareness. Lower-than-expected concentrations of volatile anesthetics are sufficient to maintain appropriate a clinical anesthesia effect during combined general-epidural anesthesia under auditory-evoked potential monitoring.

Effects of obesity on wash-in and wash-out kinetics of sevoflurane

Effects of obesity on wash-in and wash-out kinetics of sevoflurane

Effects of obesity on wash-in and wash-out kinetics of sevoflurane

Effects of obesity on wash-in and wash-out kinetics of sevoflurane

Pharmacokinetics of Isoflurane: Uptake in the Brain

We studied the effect of the inspired isoflurane concentration (C_Iiso) on the pharmacokinetics of isoflurane uptake in the brain by comparing the isoflurane concentration in internal jugular-bulb blood (Jiso) with that in arterial blood (Aiso), and analyzed this by gas chromatography. Sixteen patients (aged 43–76 years) undergoing colorectal surgery were enrolled, and anesthesia was maintained with a constant C_Iiso of either 1% (group 1, n = 8) or 2% (group 2, n = 8) during the 1st hour of isoflurane anesthesia. Under constant volume-controlled ventilation, we measured the C_Iiso and the end-tidal isoflurane concentration (C_Eiso) at the mouthpiece by infrared analysis. Our results demonstrate that it takes 40 min for the brain tissue concentration to equal Aiso for 1% C_Iiso, and 50 min for 2% C_Iiso. The Aiso (and/or Jiso) for 2% C_Iiso was approximately double when compared to that for 1% C_Iiso. Except during the initial wash-in period of the functional residual capacity in the first 3 min, the differences between C_Iiso and C_Eiso revealed that the body uptake of isoflurane for 2% C_Iiso was twice that for 1% C_Iiso. These results demonstrate that the pharmacokinetics of isoflurane uptake in the brain is time-dependent for Jiso to equal Aiso, and the midpoint between Aiso and Jiso (likely representing the isoflurane concentration in brain tissue) was dependent on C_Iiso.

THE EFFECT OF FRESH GAS FLOW ON THE DELIVERED TO END-EXPIRED GRADIENT FOR ISOFLURANE AND SEVOFLURANE

S343 INTRODUCTION: The general anesthetic equation (GAEq) predicts the delivered concentration of a volatile agent into a circle system required to provide a desired constant end-expired concentration [Et] for any fresh gas flow (FGF). [1] When FGF is lowered, the discrepancy between vaporizer settings [Vap] and [Et] increases because of rebreathing. This gradient ([Vap]-[Et]) should be lower for agents with lower blood/gas solubilities. We studied the delivered concentration of isoflurane [Vapiso] and sevoflurane [Vapsevo] into a circle system required to provide a constant [Et] of iso [Etiso] and sevo [Etsevo] for 6 different FGF. METHODS: With IRB approval and informed consent, 103 ASA I-III patients undergoing surgery received either iso or sevo in O2 in a circle system. Patients were assigned to 1 of 6 groups of 8-10 patients each depending on the FGF: 0.2 (sevo only) or 0.3 (iso only) with an initial (30 s) wash-in period (FGF 4 L/min), 0.5, 1, 2, 4, or 8 L/min. After IV induction, [Etiso] and [Etsevo] of 0.65 MAC (0.75 and 1.3%) were reached as quickly as possible (by using the maximum vaporizer setting) and were maintained at 0.65 MAC by adjusting the vaporizers. [Vapiso], [Vapsevo], [Etiso], and [Etsevo] were recorded every min, and [Vap (iso)]/[Etiso] and [Vapsevo]/[Etsevo] were calculated. RESULTS: The time to reach 0.65 MAC is shown in Table 1. After 15 min the number of vaporizer adjustments needed to maintain a constant [Et] is minimal in both groups at any FGF in the ensuing 45 min. After 15 min, [Vapiso]/[Et (iso)] is almost constant (1.4-1.5) for FGF > or = 2 L/min, while [Vapsevo]/[Et (sevo)] is almost constant (1.3-1.4) for a FGF > or = 1 L/min (Fig. 1).Table 1: Time to reach 0.65 MACDISCUSSION: We documented two pharmacokinetic properties that theoretically may facilitate the use of sevo during lower FGF. At any selected FGF, [Vapsevo]/[Et (sevo)] is lower than [Vapiso]/[Etiso]. In addition, when FGF is lowered 15 min after induction with a high FGF (4-8 L/min), changing Vapsevo will not be necessary for FGF as low as 1 L/min, while Vapiso has to be increased when FGF is <or=to2 L/min. Combined with the use of anesthetic agent monitoring, a better understanding of these pharmacokinetic principles may facilitate and encourage the use of lower FGF, which reduces anesthetic waste and consequently cost.

Association of leptin and hunger-satiety ratings in obese women.

To measure leptin, insulin and cholecystokinin (CCK) concentrations in obese women on calorie restriction and to determine their correlation with hunger-satiety ratings. Although it has been proposed to play a role in appetite regulation, the effects of physiological concentrations of these hormones on hunger-satiety in humans have not yet been well established. Prospective metabolic study. A two week 'wash-in period' followed by a three-week observation period, during which each subject underwent six measurements of satiety, blood parameters and body weight. Energy Metabolism Research Unit, Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA. 22 moderately to severely overweight women (mean age: 45 +/- 8 y; body mass index (BMI): 33 +/- 6 kg/m2). Energy restriction, in the form of a 3.3 MJ (800 kcal) diet during five weeks. Fasting blood levels of leptin, insulin, glucose and CCK, fasting hunger-satiety scores and body weight. The mean (+/- s.d.) fasting serum leptin concentration at the beginning of the observation period was 26.1 +/- 15.9 ng/ml (range: 6.7-59.8 ng/ml). Leptin concentrations correlated positively with body weight (P < 0.0001). Furthermore, reductions in body weight were associated with decreases in fasting leptin levels (P = 0.002). Leptin concentrations correlated with serum levels of insulin (P = 0.0001) and CCK (P = 0.06), but in multivariate analysis including insulin, CCK and glucose, only leptin had a significant relationship with satiety (P = 0.04). This relationship was linear. These results confirm the association between leptin levels, body weight and serum insulin. We also showed that higher serum leptin levels correlated with greater feelings of fullness, a relationship which was not blunted in the more obese subjects. These findings suggest that leptin is a satiety hormone that reduces appetite, even in obese individuals, and that weight gain must be due to other factors, overriding this feed-back regulation.