Effect of body weight on the volume of distribution of theophylline

The volume of distribution (Vd) of theophylline and the relevant aminophylline loading dose (LD) are usually calculated on the basis of total body weight (TBW). In obese subjects it has been suggested that lean or ideal body weight (IBW) is the best predictor. In a sample of 40 acutely ill asthmatic patients (aged 22 to 78 yr, weighing 45 to 176 kg) we measured Vd and found that (1) it increases with TBW, (2) it cannot be accurately predicted from either TBW or IBW alone by a simple regression analysis. Power functions have been usefully applied in comparing the pharmacokinetics of animal species, including humans, with different body mass. In our sample, data were best fitted by the equation Vd = 1.29 TBW 0.74, which seems to take care of lean as well as obese patients. Results were confirmed (r = 0.89 between predicted and measured values) in a second independent sample of patients (aged 26 to 77 yr, weighing 38 to 167 kg). This helps to minimize the error in obtaining the target serum concentration of theophylline when giving a LD calculated from a predicted Vd value.     

Volume of distribution of theophylline in acute exacerbations of reversible airway disease. Effect of body weight

The literature is unclear as to whether theophylline loading doses should be based on total body weight (TBW) or ideal body weight (IBW). The objective of this study was to determine the most appropriate body weight for estimation of volume of distribution (Vd) in calculating theophylline loading dose in patients with acute bronchospasm. Fifty-four adult patients with acute bronchospasm requiring intravenous (IV) theophylline therapy were entered into the study. Patients were randomized into three theophylline loading dose groups based on (1) TBW, (2) IBW, and (3) adjusted body weight (ABW). Initial serum theophylline concentrations were used to determine an IV loading dose to reach a plasma concentration of 12 to 15 micrograms/ml. Percent prediction error was used to determine the appropriateness of each dosing group. Volumes of distribution were also determined for each group. There was a statistically significant difference at p less than 0.01 in the percent prediction error when patients in the TBW group were compared to the IBW and ABW groups. A statistically significant difference in the Vd was observed between the TBW and IBW group (p less than 0.01). We conclude that IBW is more appropriate than TBW or ABW for determining theophylline loading dose in patients with acute bronchospasm.     

Dosage of antituberculous drugs in obese patients

There are no published data defining efficacious drug therapy for obese patients with active tuberculosis. Current dosage recommendations are based on total body weight (TBW); drug toxicity might result in obese patients receiving TBW doses. Peak and trough serum levels were measured for rifampin, streptomycin, ethambutol, and pyrazinamide in an obese patient (166 kg TBW, 87 kg ideal body weight (IBW] with miliary and meningeal tuberculosis. The observed drug levels and the calculated serum half-lives of these drugs were compared with the expected serum levels and serum half-lives in lean patients treated with literature-recommended doses. The observed serum levels in our obese patients were within the expected range for lean patients when dosage was based on IBW rather than on TBW. The observed cerebrospinal fluid penetrations of the drugs studied in our obese patient were similar to those reported in lean patients.     

Digoxin disposition in obesity: Clinical pharmacokinetic investigation

Olgoxin pharmacokinetics were studied in 16 obese (mean ± SD weight, 100.2 ± 36.8 kg) and 13 control (64.6 ± 10.5 kg) subjects. all subjects had normal renal function and no other coexisting disease. After administration of 0.75 mg digoxin by intravenous intusion, multiple plasma samples obtained over the 96 hours following infusion were analyzed for digoxin concentration by radloimmunoassay. Pharmacokinetic parameters were determined by weighted iterative nonlinear least squares regression analysis. Elimination half-life ($\text{t}\text{1}\text{2}$) was not different between obese and control groups (35.6 ± 10.5 vs 41.2 ± 16.7 hours). Absolute volume of distribution (Vd) also was not different (981 ± 301 vs 937 ± 397 liters), nor was total clearance of digoxin (328 ± 82 vs 278 ± 87 ml/min). Elimination $\text{t}\text{1}\text{2}$ was significantly negatively correlated with clearance among all subjects (r = ?0.46; p < 0.01). Using percent ideal body weight (IBW) as a measure of obesity, no correlation was found between percent IBW and Vd (r = 0.03). Thus digoxin is simllarly distributed into IBW in obese and normal weight subjects, and there is no significant distribution of digoxin into excese body weight over IBW. In addition, there is no difference in total metabolic clearance or elimination half-life between obese and control subjects. Digoxin loading and maintenance dosage should be calculated on the basis of IBW, which reflects lean body mass, rather than TBW, which reflects adipose tissue weight in addition to lean body mass.     

Aminophylline loading in asthmatic patients: a protocol trial

We tested an aminophylline loading-dose protocol in which asthmatic patients presenting to an emergency department were given a half (3 mg/kg) IV loading dose based on total body weight (TBW) if they had taken a short-acting or sustained-release theophylline preparation within 12 or 24 hours, respectively, prior to arrival: otherwise, a full (6 mg/kg) loading dose was administered. Of the 28 patients given a full loading dose, 20 (71.4%) achieved a postload therapeutic level (10 to 20 micrograms/mL), and none developed a toxic level (greater than 20 micrograms/mL). Although 34 (60.7%) of 56 patients given a half loading dose attained a postload therapeutic level, 13 patients (23.2%) entered the toxic range. We were able to predict that loading doses of 7.6 mg/kg and 3.8 mg/kg based on ideal body weight (IBW) would have yielded very similar results. The mean change in theophylline level per mg/kg TBW of administered aminophylline was 2.01 micrograms/mL. When calculated on the basis of IBW, the mean change in theophylline level was 1.58 micrograms/mL. Evaluation of the change in theophylline level resulting from aminophylline loading doses based on either TBW or IBW revealed that each dosing method produced changes in blood level with similar variability that were not independent of obesity, indicating that neither dosing method is superior to the other. Thus, patients who report not having taken a theophylline preparation within the above time limits can be given a full aminophylline loading dose of either 6 mg/kg based on TBW or 7.6 mg/kg based on IBW. Other patients, however, require a preload blood level determination to optimize therapy and avoid toxic levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cimetidine Disposition in Obesity

Cimetidine pharmacokinetics were studied in 13 otherwise healthy but obese volunteers, having a mean body weight of 113 kg and a mean percentage ideal body weight (IBW) of 179%. Sixteen healthy volunteers of normal body habitus (64 kg, 99% IBW) served as controls. All subjects had normal renal function and no laboratory or clinical evidence of hepatic or cardiac dysfunction. After administration of 200-300 mg of cimetidine by rapid intravenous injection, multiple plasma samples obtained over the next 24 h were analyzed for cimetidine concentration by high pressure liquid chromatography. Elimination half-life was not different between obese and control subjects (2.23 versus 2.08 h). Apparent volume of distribution was also similar between subject groups (120 versus 106), as was total metabolic clearance (616 versus 579 ml/min). Using percentage IBW as a measure of obesity, no relationship was found between percentage IBW and apparent volume of distribution (r = 0.29). Cimetidine similarly distributes into IBW in both obese and normal weight subjects, and there is minimal distribution of cimetidine into excess body weight over IBW. Furthermore, there is no difference in total metabolic clearance or half-life of cimetidine between obese and control subjects. Cimetidine dosage in clinical practice should therefore be calculated on the basis of IBW, which better reflects lean body mass, instead of total body weight, which reflects adipose tissue weight in addition to lean body mass.     

Identifying optimal heparin management during cardiopulmonary bypass in Chinese people: a retrospective observational comparative study

Traditionally heparin is adapted according to total body weight (TBW) to providing anticoagulation during cardiopulmonary bypass (CPB), but it may be inaccurate in some patients. The medical records of 100 adult patients who received CPB in Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology over a 10-month period in 2017 were included in the retrospective study. An unfractionated heparin (UFH) bolus of 300 IU/kg TBW was injected before initiation of CPB followed by additional doses (50 to 100 IU/kg) to maintain a target activated coagulation time (ACT) of at least 480 s. We used TBW, ideal body weight (IBW), lean body weight (LBW), or body mass index (BMI) to establish and evaluate a linear model of ACT and the amount of heparin respectively. The linear fit effect of the model based on BMI on the original data is better than the others. As the instruments to measure heparin concentration is unavailable in most medical institutions in China. The new linear model based on BMI is helpful to estimate a more individualized heparin dosage in the heparinized phase and to provide useful reference to the amount of remaining heparin in the neutralization phase.

     

Adjustments in daily energy expenditure to caloric restriction and weight loss by adult obese and lean Zucker rats

The 24 h resting (postabsorptive) energy expenditure of adult female lean and obese Zucker rats was examined both at the body weights each genotype spontaneously maintained and at body weights that were reduced 6-10 percent by restricting food intake for 2 weeks to 70 or 55 percent of normal. At their normally-maintained body weight, lean rats expended energy at a daily rate appropriate to their body mass according to the Kleiber equation (predicted kcal/day = 70.0 x BW-0.75kg observed kcal/day = 70.66 x BW-0.75kg). However, expenditure rates declined significantly in the weight-reduced lean rats restricted to 70 or 55 percent of normal intake (to 64.1 and 61.3 kcal/kg0.75). The obese rats expended energy at a rate lower than predicted by the Kleiber equation prior to weight loss (49.5 x BW-0.75kg). But, rates of daily expenditure in the obese rats was further reduced by 70 or 55 percent restriction (to 43.7 and 42.4 x BW-0.75kg), a decline proportionately as large or larger than that displayed by restricted lean rats. With this reduced metabolic rate, the total daily caloric expenditure of obese rats restricted to 55 percent of normal intake approximated that of unrestricted lean rats weighing only half as much (27.8 vs 27.5 kcal/day; 569 vs 285 g). Evidently, Zucker obese rats display the same adaptive reductions in resting metabolism as do leans in response to energy deficit and weight loss. In both, these adjustments in expenditure act to stabilize body weight at the levels that typify each genotype.     

Lidocaine disposition in obesity

Fourteen obese men (mean weight 124 ± 8 kg (± standard error of the mean), percent ideal body weight (IBW) 169 ± 10%), 11 obese women (96 ± 6 kg; 174 ± 11% IBW), 19 control men (69 ± 1 kg; 93 ± 2% IBW), and 12 control women (59 ± 2 kg; 102 ± 3% IBW), all of similar age and without clinical or laboratory evidence of cardiac or renal dysfunction, received a single 25-mg intravenous dose of lidocaine. Elimination half-life was markedly prolonged in obese compared with control men (2.69 ± 0.2 vs 1.62 ± 0.06 hour, p < 0.001) and in obese compared with control women (2.95 ± 0.1 vs 2.08 ± 0.06 hour, p <0.01). This was not the result of a change in clearance (men, obese vs control: 1,427 ± 117 vs 1,346 ± 86 ml/min, difference not significant, [NS]; women: 1,089 ± 83 vs 1,162 ± 84 ml/min, NS), but rather of an increased absolute volume of distribution (Vd) in obese men (325 ± 29 vs 186 ± 12 liters, p <0.001) and obese women (264 ± 20 vs 209 ± 15 liters, p <0.025). Vd corrected for total body weight was unchanged in obesity for both men (2.67 ± 0.22 vs 2.71 ± 0.18 1/kg, NS) and women (2.88 ± 0.31 vs 3.57 ± 0.25, NS), suggesting that lidocaine Vd increases in parallel with body weight in both sexes. Because lidocaine clearance is determined mainly by hepatic blood flow, these findings suggest that extremes of body weight do not change hepatic blood flow. However, lidocaine distribution is markedly increased in obese subjects of either sex, and is distributed to the same extent into excess body weight as into IBW. Lidocaine loading doses in obese persons should be calculated based on total body weight, but infusion rate should not be changed.     

Assessment of methods for assigning treadmill exercise workloads for lean and obese women

The use of relative oxygen consumption (% VO2 max) to equate workloads between trained and untrained subjects is considered appropriate. Whether this method (% VO2 max) is correct when testing lean versus obese subjects has not been studied. Using three experimental sessions separated by at least one week we studied seven obese, nondiabetic women weighting 140 +/- 21 kg (mean +/- s.d.) and 10 lean women of similar age weighing 51 +/- 5 kg during treadmill walking. Body fat determined by hydrostatic weighing was 50 +/- 7 and 23 +/- 7 percent in obese and lean groups, respectively (P less than 0.05). Absolute maximal VO2 (VO2 max) in obese women (3.18 +/- 0.28 l/min) significantly exceeded VO2 max for lean women (2.45 +/- 0.31 l/min, P less than 0.05). However, in obese women VO2 max relative to total body weight (TBW) was lower (P less than 0.05) while VO2 max relative to fat-free weight (FFW) was similar to corresponding values for lean women. Submaximal treadmill exercise at 75m/min with 0, 5 and 10 percent inclines resulted in higher VO2 (l/min) and heart rate (HR) in the obese group (P less than 0.05). At each incline VO2 relative to BW was significantly lower in the obese (P less than 0.05) yet significantly higher when expressed relative to FFW (P less than 0.05). The relationship between HR and %VO2 max was similar for lean and obese. Ten minutes of walking at 70% VO2 max resulted in no significant differences between the groups in the 10 min values for HR, total work done, rise in rectal temperature, plasma lactic acid, perceived exertion and oxygen consumption relative to FFW. We conclude that either fixed absolute workloads or fixed oxygen consumption (absolute or relative to BW or FFW) are inappropriate methods for equating workloads when lean and obese subjects are compared. Relative VO2 accurately defines physiologically comparable exercise intensities for these groups and this should be the method of preference when studies are designed to investigate metabolic, endocrine or cardiovascular similarities and/or differences between these groups.     

Prevalence and consequences of nutritional depletion in lung transplant candidates.

Nutritional status was studied in lung transplant (LT) candidates. The hypotheses were that nutritional depletion was highly prevalent and lean body mass depletion was a risk factor for a higher mortality both before and after LT. Of 78 consecutive patients listed for LT, 16 (21%) died while on the waiting list, eight (10%) were alive awaiting LT, and 54 (69%) received a graft. Mean age was 42.3+/-4.4 (mean+/-SD). Thirty-eight per cent had a diagnosis of bronchiectasis or cystic fibrosis (BRO/CF), 33% of emphysema, 20% of idiopathic pulmonary fibrosis (IPF) and 8% of primary pulmonary hypertension. Body mass index (BMI) was 20.4+/-4.3 kg.m2, weight was 87.9+/-16.6% of ideal body weight (IBW). Patients were classed into four nutritional groups according to IBW and creatinine height index (CHI): 1: weight <90% IBW and CHI <60% of predicted (28% of cases); II: weight <90% IBW and CHI > or =60% (27%); III: weight > or =90% IBW and CHI <60% (17%); IV: weight > or =90% IBW and CHI > or =60% (28%). Overall, 72% were depleted corresponding to groups 1, II and III. Lean body mass depletion occurred despite normal weight in 17% of the cases (group III). Subjects with BRO/CF were mostly in groups 1, II, III whereas IPF were concentrated in group II. Lean body mass depletion was associated with more severe hypoxaemia, reduced 6-minute walking distance and a higher mortality while awaiting. After LT, duration of mechanical ventilation, time spent in intensive care unit (ICU) was related to initial body composition. Survival after LT was lowest in group III. To conclude, nutritional depletion in lung transplant candidates is highly prevalent and should be more precisely assessed with a special reference to lean body mass since it has specific consequences both while awaiting and after lung transplant. Attempts should be made to increase lean body mass before lung transplant.     

Decreased serum osteoprotegerin levels in patients with cardiac syndrome X

Receptor activator of nuclear factor KB (RANK) and osteoprotegerin (OPG) represent the ligand and decoy receptor, respectively, of a pleiotropic cytokine system that regulates bone metabolism and vascular biology. Several studies supported systemic microvascular abnormalities in patients with cardiac syndrome X (CSX). This study investigates serum OPG levels in healthy obese subjects and healthy lean controls affected by cardiac syndrome X. METHODS: We compared the OPG levels in 8 patients with cardiac syndrome X [2 males, 6 females; age: 46+/-6 yr; body mass index (BMI): 30+/-5 kg/m2] with 24 obese subjects (8 males, 16 females; age: 38+/-5 yr; BMI: 35+/-5 kg/m2) and 15 healthy lean controls (6 males, 9 females; age: 36+/-5 yr; BMI: 23+/-2 kg/m2; BMI<25kg/m2). RESULTS: Serum OPG levels in patients with cardiac syndrome X were lower than those in obese subjects and lean controls (11.45+/-8.36 pg/ml, 14.78+/-8.22 pg/ml, 19.24+/-6.96 pg/ml, respectively, cardiac syndrome X vs lean controls, p=0.039). CONCLUSIONS: Serum OPG levels are lower in patients with CSX. Further studies on the mechanisms of OPG in microangiopathy may help to evaluate the OPG system role as a marker for disease activity, prognosis and response to therapy in cardiovascular diseases.     

Leptin and bone mineral density: a cross-sectional study in obese and nonobese men

Leptin has been suggested to decrease bone mineral density (BMD). This observational analysis explored the relationship between serum leptin and BMD in 327 nonobese men (controls) (body mass index 26.1 +/- 3.7 kg/m(2), age 49.9 +/- 6.0 yr) and 285 juvenile obese men (body mass index 35.9 +/- 5.9 kg/m(2), age 47.5 +/- 5.1 yr). Whole-body dual-energy x-ray absorptiometry scan measured BMD, fat mass, and lean mass. Fasting serum leptin (nanograms per milliliter) was strongly associated with fat mass (kilograms) in both controls (r = 0.876; P < 0.01) and juvenile obese (r = 0.838; P < 0.001). An inverse relation between BMD adjusted for body weight and serum leptin emerged in both the control group (r = -0.186; P < 0.01) and the juvenile obese group (r = -0.135; P < 0.05). In a multiple linear regression, fat mass, lean body mass, and occupational physical activity were positively associated with BMD in the control group, whereas in the juvenile obese, only lean body mass was positively associated with BMD and smoking negatively associated with BMD. Our study supports that leptin is inversely associated with BMD and may play a direct role in the bone metabolism in nonobese and obese Danish males, but it also stresses the fact that the strong covariation between the examined variables is a shortcoming of the cross-sectional design.     

Basal metabolism of obese adolescents: age, gender and body composition effects

Body composition (percent fat and lean body mass) and basal metabolic rates were determined in 67 obese adolescents ranging in age from 10 to 16 years (30 male, 37 female). Basal oxygen uptake was determined on rising in the morning using open-circuit spirometry with a 10-min collection period. Body composition was determined from body density measurements using the underwater weighing procedure. There were no male-female differences (except for basal VCO2 production, P less than 0.05) for any body composition or metabolic variable. The subjects' (male and female) average weight was 73 kg, height--157 cm, percent fat--40 percent, fat weight--30 kg, lean body mass--92 kg, and kcal/24 h--1535. Correlations between age, body composition and basal energy expenditure were all moderate to low (r less than or equal to 0.78). In contrast to adult data, lean body mass was not highly correlated to basal energy expenditure suggesting that perhaps there is a 'metabolic condition' of the obese adolescent modulated by excess fatness or the instability of the body cell mass. Stepwise multiple linear regression revealed that for the obese male adolescent, body surface area and percent fat, and for the obese female adolescent body surface area and body weight resulted in the best prediction of basal kcal/24 h. The standard errors of prediction were +/- 17.9 percent for the males, and +/- 14.4 percent for the females.     

Growth hormone secretion and leptin in morbid obesity before and after biliopancreatic diversion: relationships with insulin and body composition

Obesity is characterized by increased leptin levels and insulin resistance, whereas blunted GH secretion is paired with normal, low, or high plasma IGF-I levels. To investigate body composition in human obesity and the interactions among the GH-IGF-I axis, leptin, and insulin resistance [measured with the homeostasis model assessment (HOMA) score], we studied 15 obese females, aged 23-54 yr (mean age, 42.7 +/- 2.6), with a body mass index (BMI) of 44.02 +/- 1.45 kg/m(2), who underwent treatment by biliopancreatic diversion (BPD), before and after surgery (16-24 months; BMI, 28.29 +/- 0.89 kg/m(2)). Our controls were 15 normal females, aged 28-54 yr (mean age, 40.8 +/- 2.3 yr), with a BMI of 27.52 +/- 0.53 kg/m(2). Insulin and leptin levels and HOMA scores were higher pre-BPD than in the controls. The GH response to GHRH was blunted, with a GH peak and GH area under the curve (AUC) significantly lower than those in controls. IGF-I and IGF-binding protein-3 (IGFBP-3) were also lower than control values. After surgery, BMI, fat mass, lean body mass, HOMA, insulin, and leptin significantly decreased. Furthermore, the GH response to GHRH severely increased; IGF-I and IGFBP-3 levels did not significantly vary. Considering all subjects, correlation analysis showed a strong positive correlation between insulin and leptin, and a negative correlation between insulin and GH peak and between insulin and GH AUC. Regression analysis performed grouping pre- and post-BPD indicated that leptin and GH peak or AUC could best be predicted from insulin levels. The surgical treatment of severe obesity after stabilization of body weight decreases BMI and fat mass while preserving normal lean body mass as well as positively influencing insulin sensitivity and thus aiding the normalization of leptin levels. The insulin reduction may be mainly involved in the increase in the GH response to GHRH through various possible central and peripheral mechanisms while decreasing the peripheral sensitivity to GH itself, as shown by the stable nature of the IGF-I and IGFBP-3 values. Our findings suggest that the changes in insulin levels are the starting point for changes in both leptin levels and the somatotrope axis after BPD.     

Creatine kinase and creatine kinase-MB isoenzyme during and after exercise testing in normal and obese young people.

We report creatine kinase (CK) and CK-MB values during a cycloergometric test up to maximal work capacity in 10 normal subjects aged 20 to 39 years (mean body mass index, 22 kg/m2) and 11 obese patients aged 17 to 42 years (mean body mass index, 41 kg/m2), all without any cardiorespiratory diseases. Total CK was significantly higher in obese patients. The CK-MB was not significantly different between the two groups, except at the first recovery when it was increased in obese patients and decreased in normal subjects. These results could be due to more important total stress of the total musculature, especially cardiac, and especially cardiac musculature in obese patients during a physical effort. Considering the mean values of total CK of our obese patients, it may be possible that they have myocardial damage at percentages of CK-MB less than those of lean subjects generally accepted at more than 4 percent. Moreover, in obese heart patients myocardial distress during exercise testing may be present despite heart rate at peak exercise beneath the theoretic maximal.     

Relationship of plasma sex hormones to different parameters of obesity in male subjects

Relationships between plasma sex hormones and different parameters of obesity (weight, ideal body weight [IBW], overweight, fat mass, and body surface) were investigated in 70 healthy nonobese and obese males, 20–40 yr of age and with a body weight of 85%–245% of IBW. Plasma sex hormones remained unaffected by weight up to approximately 160% of the IBW. Only in the massively obese subjects was plasma testosterone decreased to 40% of controls (from 6.2 to 2.5 ng/ml), whereas free testosterone remained almost constant. On the other hand, plasma estrone and estradiol exhibited significant increases in obese subjects, ranging from 31.5 ± 5.3 to 52.3 ± 5.8 pg/ml for estrone, and 25.4 ± 5.4 increasing to 44.7 ± 5.0 pg/ml for estradiol. Similarly, free estradiol was shown to significantly increase with obesity in men from 505 ± 118 to 991 ± 123 fg/ml (p < 0.001). The ratios of testosterone/androstenedione, as well as of estradiol/estrone, were not affected by obesity, suggesting that reduction of the 17-oxo-group of the steroids is not influenced by the amount of fat tissue. A significant (p < 0.001) correlation was found between IBW and estrone (r = 0.80) and estradiol (r = 0.75), as well as the ratios of estrone/androstenedione (r = 0.62) and estradiol/testosterone (r = 0.86). This is consistent in its evidence indicating that fat tissue may be able to aromatize androgens. In the obese subjects, there were significant correlations between plasma sex hormones (testosterone, estrone, estradiol, and free estradiol) and the parameters of obesity used. Among these, correlations were best with IBW, overweight, and fat mass (r = 0.74–0.89; p < 0.001); body weight and body surface were less favorable.     

Intravenous unfractionated heparin dosing in obese patients using anti-Xa levels

There is limited guidance on intravenous dosing of unfractionated heparin in obese patients. The purpose of this study was to determine the efficacy and safety of a standard unfractionated heparin (UFH) protocol in obese patients based on total body weight (TBW) or adjusted body weight (ABW) to reach two consecutive therapeutic anti-Xa levels. This was a retrospective observational cohort study conducted in a large academic medical center. Adults received a standard UFH protocol between January 1, 2013 to December 31, 2015. Inclusion criteria included age ≥ 18 years of age, weight ≥ 100 kg with a BMI ≥ 30 kg/m², and received intravenous UFH. Patients were excluded if they received an alternative UFH protocol, received?<?24 h of the standard UFH protocol, or had inadequate compliance to protocol. Out of the 131 patients included, 109 patients reached two consecutive therapeutic UFH levels within 96 h. The average time to two consecutive therapeutic UFH levels was 29.4 h and 27.6 h in patients dosed by TBW and ABW, respectively (95% CI ??4.63 to 8.11; P?=?0.93). Safety outcomes included major bleeding, overt bleeding, or death events between patients dosed by TBW compared to ABW, (p?=?0.61, p?=?1.0, p?=?1.0, respectively). Dosing intravenous UFH based on TBW or ABW resulted in similar times to therapeutic anti-Xa levels and safety outcomes. The data provided suggests using either TBW or ABW in obese patients is as effective and safe to use.

     

Distribution of muscle mass and maximal exercise performance in patients with COPD

STUDY OBJECTIVE: To investigate the distribution of reduction in lean body mass (LBM) and whether LBM in legs (LBMlegs) can be a determinant of maximal exercise performance in COPD patients. METHODS: Thirty-eight male outpatients with COPD (mean +/- SD FEV1, 47.4 +/- 24.0% of predicted) who underwent complete pulmonary function testing were classified into two groups according to FEV1 expressed as a percentage of predicted value. Group A comprised 21 patients with mild-to-moderate airflow limitation (FEV(1) > or =35% predicted), and group B comprised 17 patients with severe airflow limitation (FEV1 < 35% predicted). LBM, which represents skeletal muscle mass, was measured by dual energy x-ray absorptiometry (DXA) and was assessed separately in arms, legs, and trunk. Maximal oxygen uptake VO2max was measured during maximal exercise on a cycle ergometer. RESULTS: LBM in each region was expressed as a percentage of ideal body weight (IBW). LBM in arms (LBMarms)/IBW, LBMlegs/IBW, and LBM in trunk (LBMtrunk)/IBW were significantly depleted in group B compared with group A (p < 0.01). LBMlegs expressed as a percentage of total LBM (LBMlegs/total LBM) was significantly lower in group B (p < 0.05), although there was no significant difference in LBMarms/total LBM and LBMtrunk/total LBM between the two groups. VO2max correlated significantly with LBMlegs/IBW in group A, but not in group B. By stepwise regression analysis, LBMlegs/IBW appeared to be a significant predictor of VO2max in group A, while not in group B. CONCLUSION: LBMlegs was a significant predictor of maximal exercise performance in patients with mild-to-moderate airflow limitation, but not in patients with severe airflow limitation who had disproportional reduction in LBMlegs.     

Ethambutol-induced optical neuropathy: risk of overdosing in obese subjects

BACKGROUND: Ethambutol (EMB) is one of the first-line drugs in the treatment against tuberculosis (TB). Side-effects are infrequent, but its main adverse effect, optical neuropathy, has long been recognised. The mechanisms of action and predisposing factors have not yet been fully understood. METHOD: We conducted a retrospective study (1992--2007) in an attempt to find predisposing factors for optical neuropathy. RESULTS: Visual disturbance was reported in 1.3% of the 760 patients treated with EMB; of these, 0.8% were EMB-related. We present the six cases; four were clearly overdosed, but in two obese patients dosage was correctly calculated for total body weight (TBW). CONCLUSION: Analysis of the case histories and previous reports suggest that optical neuropathy may at least partly be caused by EMB overdosing due to daily dosing based on TBW instead of dosing on lean body mass.