Basis Of Ideal Body Weight Research Articles

Sugammadex and ideal body weight in bariatric surgery: the debate continues.

I read with great interest the paper by Sanfilippo et al., evaluating the safety and efficacy of sugammadex administered on the basis of ideal body weight (IBW) to reverse neuromuscular blockade (NMB) at the reappearance of second twitch during train-of-four (TOF) stimulation [1]. However, this study raises several issues that deserve comment. First, the authors chose a TOF ratio of 0.9 after sugammadex administration based on IBW as their primary endpoint [1]. A TOF ratio of 0.9 may not indicate full recovery, as this ratio can be associated with impaired neuromuscular transmission [2], inhibition of the hypoxic ventilatory response, and upper airway or pharyngeal dysfunction [3]. Based on acceleromyography studies, the current recommendation is that a TOF ratio greater than or equal to 1.0 should be used to confirm complete recovery from NMB [3]. Second, the TOF ratio observed before tracheal extubation was 0.90 ± 0.57 in the IBW group compared to 0.91 ± 0.08 observed in the real body weight (RBW) group [1]. Considering the standard deviation from the mean value, not all patients reached a TOF ratio greater than or equal to 0.9 before tracheal extubation in the IBW group [1]. In another study, a single dose of sugammadex based on IBW was associated with failure to achieve a TOF ratio greater than or equal to 0.9 in 23% and 40% of patients who had moderate and deep NMB, respectively [4]. These patients required a rescue dose of sugammadex, indicating that a high percentage of slow responders should be expected in obese patients and that there is potential risk of blockade reoccurrence [4]. Finally, the median time for recovery to a TOF ratio of 0.9 was slower in the IBW group than in the RBW group (151 ± 44 versus 121 ± 55 sec) [1]. Even if signs of residual curarization were not observed in the patients enrolled in the study [1], however, a slow recovery may be an expression of the ineffectiveness of the dose of sugammadex [5, 6] and the combination of underdosing and delayed response may be associated with recurarization [6]. So, the reversal of NMB with sugammadex dosed on the basis of IBW in obese patients requires a special observation in the postoperative period, being obese patients at risk of potential upper airway obstruction and respiratory failure [3–6]. Therefore, IBW does not appear to offer a proper dosing scalar for sugammadex administration in obese patients and requires close surveillance and neuromuscular monitoring during the postoperative period [3–6]. In contrast, with sugammadex administered on the basis of RBW, obtaining a TOF ratio greater than or equal to 1.0 with acceleromyography is a relatively easy goal to achieve [5–7]. Thus, the current evidence suggests that sugammadex administered to reverse NMB at the reappearance of second twitch during TOF stimulation on the basis of RBW has the full potential for improving care and safety of obese patients.

Rocuronium for rapid sequence induction in morbidly obese patients

Rocuronium for rapid sequence induction in morbidly obese patients

Revised Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy

The American Academy of Ophthalmology recommendations for screening of chloroquine (CQ) and hydroxychloroquine (HCQ) retinopathy were published in 2002, but improved screening tools and new knowledge about the prevalence of toxicity have appeared in the ensuing years. No treatment exists as yet for this disorder, so it is imperative that patients and their physicians be aware of the best practices for minimizing toxic damage. New data have shown that the risk of toxicity increases sharply toward 1% after 5 to 7 years of use, or a cumulative dose of 1000 g, of HCQ. The risk increases further with continued use of the drug. The prior recommendation emphasized dosing by weight. However, most patients are routinely given 400 mg of HCQ daily (or 250 mg CQ). This dose is now considered acceptable, except for individuals of short stature, for whom the dose should be determined on the basis of ideal body weight to avoid overdosage. A baseline examination is advised for patients starting these drugs to serve as a reference point and to rule out maculopathy, which might be a contraindication to their use. Annual screening should begin after 5 years (or sooner if there are unusual risk factors). Newer objective tests, such as multifocal electroretinogram (mfERG), spectral domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF), can be more sensitive than visual fields. It is now recommended that along with 10-2 automated fields, at least one of these procedures be used for routine screening where available. When fields are performed independently, even the most subtle 10-2 field changes should be taken seriously and are an indication for evaluation by objective testing. Because mfERG testing is an objective test that evaluates function, it may be used in place of visual fields. Amsler grid testing is no longer recommended. Fundus examinations are advised for documentation, but visible bull's-eye maculopathy is a late change, and the goal of screening is to recognize toxicity at an earlier stage. Patients should be aware of the risk of toxicity and the rationale for screening (to detect early changes and minimize visual loss, not necessarily to prevent it). The drugs should be stopped if possible when toxicity is recognized or strongly suspected, but this is a decision to be made in conjunction with patients and their medical physicians.

Implications of Body Weight Calculations for Autologous Peripheral Blood Stem Cell Transplantation.

Background: Obesity is a prevalent health problem and significant heterogeneity is seen in the body weight and BMI among adult patients undergoing autologous stem cell transplantation (SCT). At least two critical steps of the SCT are influenced by the body weight. Stem cell collection targets are usually determined based on the actual body weight and conditioning chemotherapy doses are usually determined based on corrected ideal body weight. One could hypothesize that since the stem cells home to bone marrow, the ideal body weight (IBW) being based on the height may be a better indicator of the stem cell numbers required rather than the actual body weight (ABW). Since chemotherapy doses are calculated based on corrected ideal body weight, and the volume of distribution is higher in obese patients, these patients may have decreased drug exposure and hence a higher risk of progression.Methods: We retrospectively evaluated the engraftment kinetics and response outcome of 306 SCTs done at our institution between March 1998 and October 2001. These included patients who had undergone SCT for multiple myeloma (46%), NHL (34%), HD (6%) and AL amyloidosis (14%). Body weight, height, stem cell dose and engraftment data was obtained from medical records. The stem cell dose received was calculated based on their ABW as well as IBW and correlated with the time to white cell and platelet engraftment. We also evaluated the effect of BMI on the progression free survival after the stem cell transplant using various cut offs.Results: The mean (range) for the ABW, IBW and BMI were 46.6 kg to 189 Kg; 45.5 kg to 94 kg; and 17.5 to 55.8 respectively. Using logistic regression, we estimated the ability of CD34 cell dose by actual and ideal body weight to predict the likelihood of platelet engraftment (50,000) by day 21 post transplant. The coefficients using both the doses were very similar (.391 for ideal and 0.361 for actual). Using Receiver operating characteristic analysis (ROC analysis); we determined the stem cell dose cutoff that best predicted for failure to engraft neutrophils by 21 days post transplantation, median CD34 dose by ABW of 3.6 million/Kg and by IBW of 4.2 million/Kg. Similarly, for failure to engraft platelets by day 30 the cutoffs were 2.89 million/Kg by actual weight and 3.77 million/kg by ideal weight. Among the individuals with actual body weight more than 25% of ideal body weight (n=122, 40%), we calculated the optimal total CD34 dose required and compared to the actual dose infused using both the cutoff sets (286 million vs. 446 million, P < 0.001 using ANC cutoff and 251 million vs. 446 million using the platelet cutoff, P < 0.001). We then examined the effect of BMI on progression free and overall survival from transplant. The progression free and overall survival post transplant was similar for patients with BMI over 30 kg/m2 compared to those below this cutoff. There was no difference when patients with myeloma or lymphoma were studied separately.Conclusion: This study, as in previous studies, confirms that stem cell dose determined on the basis of ideal body weight is comparable to that by actual body weight in terms of engraftment kinetics. In patients significantly above the ideal body weight, it is reasonable to use a target based on ideal body weight which will allow for collection of less numbers of CD34 cells, thus conserving resources. Among patient undergoing stem cell transplant, the practice of using corrected ideal body weight does not appear to compromise the outcome of stem cell transplant.

Pharmacokinetics of quinine in obesity

Obesity can modify the pharmacokinetics of lipophilic drugs. As quinine is a lipophilic drug, this study was conducted to determine whether the pharmacokinetics of quinine is altered in obese subjects. Nine obese Thai men were compared with 8 age-matched lean men. After an oral dose of quinine had been given to the men, plasma quinine concentrations were measured up to 48 h after the dosing. Mean peak plasma quinine concentration in the obese group was significantly lower than that observed in the controls (4·0 ± 0·8 vs 5·0 ± 0·3 mg/L, P < 0·01). There were no significant differences in time to reach the peak plasma concentration, half-life and total clearance of quinine between the 2 groups. The mean clearances of quinine normalized to the ideal bodyweight (IBW) in the obese and the control groups were not significantly different (0·091 ± 0·018 vs 0·091 ± 0·024 L/h/kg IBW, P > 0·05). As there are similarities in the total clearance and the clearance of quinine based on IBW, the maintenance dose of quinine should be given to obese patients on the basis of ideal bodyweight, not on total bodyweight.

Detection and Prevention of Maculopathy Associated with Antimalarial Agents

Rheumatologists use both cholorquine and hydroxychloroquine in the treatment of systemic arthritic and immune disease. Hydroxychloroquine is much more expensive but is better tolerated by patients. My experience in watching patients being switched from one drug to another suggests that chloroquine is more effective in some patients than is hydroxychloroquine. Reynes thought that a review of the literature suggests that chloroquine is more toxic at 250 mg/day as compared to 400 mg of hydroxychloroquine if dose is based on these dosages. This theory may be related, in part, to the observation by Raines and associates that chloroquine crosses the blood-retinal barrier whereas hydroxychloroquine does not. Patients should be assessed 6 months after starting antimalarials. Routine automated perimetry is not indicated. An appropriate examination would include visual acuity testing, color-vision testing, Amsler grid testing, and corneal assessment. Patients should be dosed on the basis of ideal body weight (not actual body weight) to reduce the incidence of macular toxicity. Patients with no risk factors should be examined no more than once a year.

The Pharmacokinetics of Vecuronium in Male and Female Patients

To evaluate the effect of gender on the pharmacokinetics of vecuronium, we studied 30 patients (15 male and 15 female) undergoing elective plastic surgery with anticipated surgical blood loss of <300 mL under general anesthesia.General anesthesia was induced with thiopental 4-6 mg/kg and fentanyl 2-4 [micro sign]g/kg and was maintained with 60% nitrous oxide in oxygen and an end-tidal concentration of 1.5%-2% enflurane. After a 2-min infusion of vecuronium 100 [micro sign]g/kg, a modified fluorometric assay was used to determine the plasma concentrations of vecuronium for 5 h. The results showed that, compared with women, the plasma concentrations of vecuronium in men were significantly lower during the first 20 min and that the disposition kinetics of vecuronium can be best described mathematically by a three-compartment open model in the two groups. The volume of the central compartment and the volume of distribution at steady state were 39.6 +/- 8.6 and 164.8 +/- 29.3 mL/kg, respectively, in women. These values increased significantly to 54.4 +/- 14.4 and 201.4 +/- 75.8 mL/kg in men (P < 0.05). When the data were calculated on the basis of ideal body weight, the volume of distribution of vecuronium was also different between men and women (P < 0.05. The half-lives of fast distribution and distribution, the elimination half-life, mean residual time, area under the plasma-concentration curve, and plasma clearance were not different between the two groups. We conclude that the pharmacokinetics of vecuronium are significantly different between genders and that and men have the greater volume of distribution of vecuronium. Implications: The authors found that, compared with women, men had lower plasma concentrations of vecuronium after the IV administration of vecuronium and a larger volume of distribution of vecuronium. The pharmacokinetic differences may be related to the differences in the sensitivity to vecuronium between genders. (Anesth Analg 1998;86:1322-7)

The conservative management of chronic renal failure: Results of a recent survey

Opinions differ regarding the role of protein restriction in the progression of renal disease. Unfortunately the Modification of Diet in Renal Disease Study did not settle this controversy. To assess the use of low protein diets (LPDs) in the United Kingdom, renal dietitians were surveyed about the current dietetic practices and beliefs in their Renal Units. In the survey, 81% of questionnaires were returned (59 of 73), of these 35 Renal Units were using LPDs (<1 g/kg body weight). The majority (33) used LPDs for symptomatic relief and 20 for slowing progression. The use of LPDs in diabetic patients was similar to nondiabetic patients, but LPDs were started earlier by 12 Renal Units. Most (22) of the dietitians calculate LPDs on the basis of ideal body weight. Nutritional assessment was by weight (35), body mass index (26), serum albumin (31), and upper arm anthropometry (10). The lack of agreement, both within and outside of Renal Units will ensure that the debate regarding protein restriction continues.

Pharmacokinetics and pharmacodynamics of methylprednisolone in obesity

Methylprednisolone pharmacokinetics and its directly suppressive effects on plasma cortisol, blood histamine (basophils), and circulating helper T cells were evaluated in six obese (at least 35% above ideal body weight) men and six nonobese male volunteers. Methylprednisolone doses of 0.6 mg/kg total body weight were administered as the 21-succinate sodium salt. Absolute clearance (in liters per hour) of methylprednisolone was 40% less in the obese subjects. Total volume of distribution (Vss) of methylprednisolone was unchanged (about 120 L), but when normalized for total body weight, Vss per kilogram was less in obesity. The patterns of cortisol, blood histamine, and helper T cell responses after methylprednisolone administration were similar in both groups, but more profound effects were observed in the obese subjects. Pharmacodynamic models were applied for these immediate effects of methylprednisolone based on the premise that receptor interactions of steroids are followed by rapid suppression of the circadian rhythm of cortisol and recirculation of basophils and helper T cells, which persist until inhibitory concentrations (IC50) of methylprednisolone disappear. Similar IC50 values for the three effects were obtained in both groups, indicating no intrinsic pharmacodynamic differences in sensitivity to these methylprednisolone effects in obesity. However, methylprednisolone should be administered on the basis of ideal body weight, and the dosing interval should be potentially lengthened because of decreased methylprednisolone clearance in obesity.

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 ( t 1 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 t 1 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.