The Identification of Malnutrition in Heart Failure Patients

2002 ◽  
Vol 1 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Sandra M. Nicol ◽  
Diane L. Carroll ◽  
Carol M. Homeyer ◽  
Colleen M. Zamagni
Keyword(s):  
Heart Failure ◽  
Gastrointestinal Symptoms ◽  
Ideal Body Weight ◽  
Clinical Parameters ◽  
Convenience Sample ◽  
Electrical Bioimpedance ◽  
Skinfold Measurement ◽  
Ideal Body ◽  
The Mean ◽  
Mean Heart Rate

Heart failure (HF) is the only cardiovascular disease that is increasing in incidence, prevalence, and mortality. One of the major complications associated with HF is malnutrition. Fluctuations due to fluid make weight measurement an inaccurate parameter to identify malnutrition. Therefore, the purpose of this study is to assess clinical parameters that could assist in the recognition of malnutrition in HF patients. A convenience sample of 50 HF patients had anthropometric measurements, a review of their serum chemistry levels, a collection of standard hemodynamic measures plus electrical bioimpedance, and, each subject completed a gastrointestinal symptoms assessment with two meals. Eighteen (36%) subjects were classified as malnourished based on the selected criteria of a serum albumin <3.0 g/dl and/or being less than 90% of ideal body weight. Within this sample of malnourished subjects, 44% of the subjects were found to be obese based on skinfold measurement. A comparison between malnourished/not malnourished groups found that the mean heart rate was higher in the malnourished group (85 vs. 73 beats/min; P<0.017). There were no other parameters that differentiated between these groups. These results demonstrate the need for further research to identify predictive clinical parameters for malnutrition in this vulnerable population.

Therapeutic Drug Monitoring (TDM) of IV Busulfan in Patients with Severe Obesity.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1990-1990
Author(s):  
Donald A. Hutcherson ◽  
Jolynn K. Sessions ◽  
Ronald A. Mihelic ◽  
Katherine Sanvidge ◽  
Stephen R. Stricker ◽  
...  
Keyword(s):  
Body Weight ◽  
Severe Obesity ◽  
Package Insert ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Actual Weight ◽  
Severely Obese ◽  
Ideal Body ◽  
The Mean ◽  
Dosing Strategy

Abstract It has been previously reported that increases in relapse and graft rejection can be associated with a low busulfan area under the curve (AUC) and hepatic toxicities are associated with a high AUC. This has lead to strategies to adjust busulfan dosing to achieve a target AUC. A retrospective analysis was performed in patients with severe obesity, defined as a Body Mass Index (BMI) greater than 40, to evaluate the reliability of IV busulfan dosed using the package insert dosing strategy to reach a targeted AUC. The study included 11 females and 8 males who received IV busulfan as part of their hematopoietic progenitor cell transplant preparative regimen. There were 11 autologous and 8 allogeneic transplants for lymphoma (10) and leukemia (9). The mean and median ages were 38 and 41 years (range 19–51). The mean and median BMIs for this population were 47.8 and 46.2 (range 40.4–62.7). The mean and median weights were 139.5 kg and 142.5 kg (range 107–192.3). TDM was performed with the first dose of busulfan along with subsequent dosage adjustments to achieve a target AUC of 1150–1350 micromol X min/L. Busulfex package insert dosing recommendations are for 16 doses of 0.8 mg/kg (12.8 mg/kg) using an adjusted ideal body weight (AIBW) for obese patients. AIBW = 0.25 × (actual weight − ideal body weight) + ideal body weight. Using the AIBW dosing, the mean starting dose to actual body weight ratio was 0.48 mg/kg (range 0.40–0.55 mg/kg). Based on the AUC analysis, the predicted mean AUC using the AIBW dosing was 972 (range 702–1356). Six AUCs were below 900, 10 AUCs were above 900 but below 1150, 2 AUCs were within the target range and 1 AUC was greater than 1350. Thirteen of the patients had repeat AUC analyses following a subsequent dose to confirm that the dose adjustments achieved the targeted AUCs. Seven of these patients had further dose adjustments following the repeat AUC analysis. Five patients with a busulfan mean half-life of 235 minutes (range 218–247 minutes) had higher AUCs than the rest of the group. The mean and median AUCs for these 5 patients were 1177 and 1223 (range 997–1357). The remaining 14 patients with a mean busulfan half-life of 177 minutes (range 151–201) had mean and median AUCs of 899 and 903 (range 702–1105). The total therapy delivered ranged from 12.7 to 21.4 mg/kg based on the AIBW. When calculated on actual weight, the range was 6.9 to 11.24 mg/kg. Conclusion: The AIBW dosing strategy of IV busulfan is inadequate to achieve the targeted AUC of 1150–1350 in severely obese patients. Severely obese patients require dose increases in the majority of cases, while those with delayed clearance could be overdosed if higher doses are administered without TDM. Severely obese patients require TDM and the majority will require dosage adjustments to administer IV busulfan in the targeted therapeutic range.

scholarly journals Comparisons among old and new provocative tests of GH secretion in 178 normal adults

2000 ◽  
pp. 347-352 ◽  
Author(s):  
G Aimaretti ◽  
C Baffoni ◽  
L DiVito ◽  
S Bellone ◽  
S Grottoli ◽  
...  
Keyword(s):  
Low Dose ◽  
Adult Population ◽  
Ideal Body Weight ◽  
Normative Values ◽  
Gh Secretion ◽  
The Third ◽  
Ideal Body ◽  
The Mean ◽  
Age Range ◽  
Normal Adults

Classical provocative stimuli of GH secretion such as insulin-induced hypoglycaemia, arginine, clonidine, glucagon and levodopa have been widely used in clinical practice for approximately 30 years. On the other hand, in the last 10 years new potent stimuli of GH secretion have been proposed, but an extensive comparison with the classical ones has rarely been performed, at least in adults. In order to compare the GH-releasing activity of old and new provocative stimuli of GH secretion, and to define the normative values of the GH response, in 178 normal adults (95 males, 83 females; age range: 20-50 years, all within +/-15% of their ideal body weight), we studied the GH response to: insulin-induced hypoglycaemia (ITT, 0.1IU/kg i.v.), arginine (ARG, 0.5g/kg i.v.), clonidine (CLO, 300 microg/kg p.o.), glucagon (GLU, 1mg i.m.), pyridostigmine (PD, 120mg p.o.), galanin (GAL, 80pmol/kg per min), GH-releasing hormone (GHRH, 1 microg/kg i.v.), GHRH+ARG, GHRH+PD, hexarelin, a GH-releasing protein (HEX, 2 microg/kg i.v.) and GHRH+HEX (0.25 microg/kg i.v.). The mean (+/-s.e.m.) peak GH response to ITT (21.8+/-2.8, range: 3.0-84.0 microg/l) was similar to those to ARG (18.0+/-1.6, range: 2.9-39.5 microg/l) or GLU (20. 5+/-2.2, range: 10.6-36.9 microg/l) which, in turn, were higher (P<0. 001) than those to CLO (8.2+/-1.6, range: 0.3-21.5 microg/l), PD (9. 6+/-1.1, range: 2.2-33.0 microg/l) and GAL (9.3+/-1.1, range: 3.9-18. 3 microg/l). The GH response to GHRH (19.1+/-1.5, range: 2.7-55.0 microg/l) was similar to those after ITT, ARG or GLU but clearly lower than those after GHRH+ARG (65.9+/-5.5, range: 13.8-171.0 microg/l) and GHRH+PD (50.2+/-4.6, range: 17.7-134.5 microg/l) which, in turn, were similar. The GH response to HEX (55.3+/-5.5, range: 13.9-163.5 microg/l) was similar to those after GHRH+ARG and GHRH+PD but lower (P<0.001) than that after GHRH+HEX (86.0+/-4.3, range: 49. 0-125.0 microg/l) which was the most potent stimulus of GH secretion. In this adult population the third centile limits of peak GH response to various stimuli were the following: ITT: 5.3; ARG: 2.9; CLO: 1.5; GLU: 7.6; PD: 2.2; GAL: 4.0; GHRH: 5.0; GHRH+ARG: 17.8; GHRH+PD: 17.9; HEX: 21.6; GHRH+HEX: 57.1. These results confirm that, among classical provocative tests of GH secretion, ITT followed by ARG and GLU are the most potent ones and possess clear limits of normality. GHRH+ARG or PD and HEX are strong stimuli of GH secretion which, however, is maximally stimulated by a combination of GHRH and a low dose of HEX. It is recommended that each test is used with appropriate cut-off limits.

Abstract P210: Weight and Body Image Perceptions in Young, Low Income Adult Latinas with Imprecise Body Mass Index Classification

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Jen Rinaldo ◽  
Erika Froelicher ◽  
Catherine Waters ◽  
Kirsten Bibbins-Domingo ◽  
Nancy Stotts
Keyword(s):  
Body Mass Index ◽  
Body Image ◽  
Body Weight ◽  
Body Dissatisfaction ◽  
Low Income ◽  
Body Satisfaction ◽  
Ideal Body Weight ◽  
Excess Weight ◽  
Ideal Body ◽  
The Mean

Introduction: Mexican American women in the US have the second highest prevalence of overweight or obesity (78.2%), 44.8% are obese, yet little research has examined the relationship between body mass index (BMI) and body satisfaction among young, low-income Latina adults. Objective: To examine the relationships between knowledge, attitudes, beliefs, and behaviors about weight, body image and excess weight. Hypothesis: We hypothesized that (1) the women would incorrectly classify BMI; (2) the majority would be obese and (3) there is no difference in body satisfaction among those with and without excess weight. Methods: A cross-sectional study with a convenience sample of 131 self-identified Latina women, ages 18 to 45 years was used from two Northern California clinics. An interview administered questionnaire assessed demographics, weight and body image. Statistical analysis included descriptive statistics, chi-square statistics, and logistic regression analysis. Results: While 31% (n=41) classified themselves as having a healthy BMI, 21% (n= 27) met the criteria. Although 58% (n=77) classified themselves as overweight, 46% (n=60) met the criteria. Although 2% (n=3) classified themselves as obese, 34% (n=44) were obese. The majority of women (67%; n=88) reported that they were not at their ideal body weight. Of those who wanted to lose weight, the mean number of pounds they would have to lose to be at their ideal body weight was 15.5 (± 16). The mean body dissatisfaction score of those with excess weight was 2.2 (± 1.1) and 0.74 (± 1.4) for those with healthy BMI. Conclusions: Most women underestimated their BMI category. Less than 6% (n=3) of obese women correctly classified themselves as obese. The misclassification and underreporting of excess weight was statistically significant (p≤ 0.05), pointing to a need for education about weight. Body dissatisfaction scores were higher in women with excess weight. Actual/current body silhouette sizes were statistically significantly associated with excess weight: (OR=2.78, 95% CI: 1.28, 6.04, p= 0.02).

scholarly journals Intraoperative physiological ranges associated with improved outcomes after major spine surgery: an observational study

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e025337
Author(s):  
Gang Li ◽  
Liang Lin ◽  
Jifang Xiao ◽  
Stanley Rosenbaum ◽  
Philip Bickler ◽  
...  
Keyword(s):  
Heart Rate ◽  
Body Weight ◽  
Observational Study ◽  
Tidal Volume ◽  
Spine Surgery ◽  
Ideal Body Weight ◽  
Convenience Sample ◽  
Physiological Variables ◽  
Improved Outcomes ◽  
Ideal Body

ObjectiveThere is inadequate information about the values of many intraoperative physiological measurements that are associated with improved outcomes after surgery. The purpose of this observational study is to investigate the optimal physiological ranges during major spine surgery.SettingA teaching hospital in the USA.ParticipantsA convenience sample of 102 patients receiving major posterior spine surgery with multilevel spinal fusion in a prone position.MethodsPhysiological variables, including but not limited to mean arterial pressure (MAP) and cerebral and somatic tissue oxygen saturation (SctO2/SstO2), were recorded. The results of these measurements were associated with length of hospital stay and composite complication data and were analysed based on thresholds (ie, a cut-off value for optimal and suboptimal physiology) and the area under the curve (AUC) values. The AUC values were measured as the area enclosed by the actual tracing and the threshold. The outcomes were dichotomised into above-average and below-average (ie, improved) categories.ResultsAnalyses based on thresholds identified the following variables associated with above-average outcomes: MAP <60 mm Hg, temperature <35°C, heart rate >90 beats per minute (bpm), SctO2 <60% and SstO2 >80%. Analyses based on AUC values identified the following as associated with above-average outcomes: MAP <70 and >100 mm Hg, temperature <36°C, heart rate >90 bpm, tidal volume (based on ideal body weight)<6 mL/kg, tidal volume (based on actual body weight) >10 mL/kg and peak airway pressure <15 cmH2O.ConclusionThe following physiological ranges are associated with improved outcomes (ie, shorter hospitalisation and fewer complications) during major spine surgery: MAP of 70–100 mm Hg, temperature ≥36°C, heart rate <90 bpm, tidal volume based on ideal body weight >6 mL/kg, SctO2 >60% and SstO2 <80%.

Theophylline Clearance in Obese Patients in Relation to Smoking and Congestive Heart Failure

1983 ◽  
Vol 17 (4) ◽  
pp. 274-276 ◽  
Author(s):  
Richard L. Slaughter ◽  
Robert A. Lanc
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Body Weight ◽  
Ideal Body Weight ◽  
Total Body Weight ◽  
Obese Patients ◽  
Ideal Body ◽  
Total Body ◽  
Nonobese Patients ◽  
Body Clearance

The effect of obesity on the total body clearance (Cltot) of theophylline was evaluated in nonsmokers and smokers with and without congestive heart failure (CHF). The obese patients were compared with similar nonobese subjects with regard to age, sex, and disease state. The total patient population numbered 150 adults. Cltot of theophylline, based on total body weight (TBW), averaged 0.60 ± 0.20 ml/min/kg in obese nonsmokers and did not differ from the nonobese, nonsmoking group. In obese nonsmoking patients with CHF, Cltot based on TBW was 0.40 ± 0.14 ml/min/kg, which was similar to Cltot values in nonsmoking CHF patients who were not obese. A trend toward a reduction in Cltot, based on TBW, as TBW increased, in nonsmoking patients with and without CHF, was observed. In contrast to the Cltot in nonsmokers, the Cltot of theophylline in obese smokers with and without CHF was similar to the Cltot values in nonobese populations only when based on ideal body weight. However, when compared with nonsmoking, nonobese patients, no differences were observed when Cltot was corrected for TBW. These findings suggest that theophylline maintenance dose can be based on TBW in obese patients who are smokers and nonsmokers (with and without CHF), using the average Cltot obtained for the nonsmoking patients with and without CHF.

scholarly journals Medical Nutrition Therapy in Ischemic Hepatitis and Acute Kidney Injury Due to Congestive Heart Failure NYHA III

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 865-865
Author(s):  
Naldi Yanwar ◽  
Agussalim Bukhari
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Total Bilirubin ◽  
Kidney Injury ◽  
Ideal Body Weight ◽  
Nutritional Therapy ◽  
Shortness Of Breath ◽  
Ischemic Hepatitis ◽  
History Of ◽  
Ideal Body

Abstract Objectives Congestive Heart Failure is a major public health problem with an estimated prevalence of 1–2% of the adult population in developed countries, rising to ≥ 10% among persons &gt; 70 years of age. The incidence of impaired liver function in the form of congestive hepatopathy and ischemic hepatitis ranges from 15% to 65% of patients with significant heart failure. Methods Mr.T, Male, 63 years old was suffered from ischemic hepatitis due to congestive heart failure NYHA III. He had history of hipertension since 2011 and a history of heart disease since 2011. The patient has reduced oral intake since 2 weeks ago and worsening 5 days ago due to decreased appetite and shortness of breath. Anthropometric examination found body length was 166 cm, ideal body weight was 59.4 Kg, Mid Upper Arm Circumference (MUAC) was 19 cm and Handgrips strength 8,6 kg. Laboratory assessments found leukocytosis (13,100 103 /ml), impaired kidney function (Ureum was 206 mg/dL and Creatinine was 3.51 mg/dl), increased transminase enzymes (SGOT 4113 U/L and SGPT 4721 U/L) and increased levels of bilirubin (Total Bilirubin 9.79 mg/dL and Bilirubin Direk 7.79 mg/dL). Results Medical Nutritional Therapy was determined with a calorie target of 1700 kcal; protein 1,4 gr/Kg ideal body weight/day; 50% carbohydrates and 30% fat, respectively. We provided oral suplementation in the form of zinc, vitamin B Complex and curcuma. The Patient was discharged after being treated for 11 days and recovered from shortness of breath and jaundice, with adequate nutritional intake (according to calorie targets), increased anthropometric parameters (MUAC was little increased 19,3 cm but handgrips strength was significantly increased to 28,3 kg), improved laboratory result including leukocytes decreased to normal (9.940 103/ml), ureum and creatinine were also turned to normal (47 mg/dL and 1,1 mg/dL, respectively), liver function was markedly decreased (SGOT 71 U/L, SGPT 468 U/L) as well as total bilirubin (2,90 mg/dL) and direct bilirubin (1,20 mg/dL). Conclusions Optimal treatment of the underlying disease (CHF) and adequate nutritional therapy could improve nutritional status and quality of life patients with CHF NYHA III with complications of ischemic hepatitis and acute kidney injury. Funding Sources The author(s) received no financial support for research, authorship, and/or publication of this article.

scholarly journals Nutritional Management Enhances the Recovery of Swallowing Ability in Older Patients with Sarcopenic Dysphagia

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 596
Author(s):  
Akio Shimizu ◽  
Ichiro Fujishima ◽  
Keisuke Maeda ◽  
Hidetaka Wakabayashi ◽  
Shinta Nishioka ◽  
...  
Keyword(s):  
Primary Outcome ◽  
Probability Model ◽  
Functional Independence Measure ◽  
Ideal Body Weight ◽  
Functional Independence ◽  
Secondary Outcome ◽  
Ideal Body ◽  
The Mean ◽  
Level Scale ◽  
Sarcopenic Dysphagia

This study assessed whether a high provided energy of ≥30 kcal/ideal body weight (IBW)/day (kg) for patients with sarcopenic dysphagia effectively improved swallowing ability and the activities of daily living (ADLs). Among 110 patients with sarcopenic dysphagia (mean age, 84.9 ± 7.4 years) who were admitted to a post-acute hospital, swallowing ability and the ADLs were assessed using the Food Intake LEVEL Scale (FILS) and the Functional Independence Measure (FIM), respectively. The primary outcome was the FILS at discharge, while the secondary outcome was the achievement of the FIM with a minimal clinically important difference (MCID) at discharge. We created a homogeneous probability model without statistically significant differences using the inverse probability of treatment weighting (IPTW) method with and without a mean provided energy of ≥30 kcal/IBW/day (kg) for a period of 1 week of hospitalization and compared the outcomes between groups. A mean provided energy of ≥30 kcal/IBW/day (kg) was achieved in 62.7% of patients. In the IPTW model, the FILS and the rates of achieved MCID of the FIM at discharge were significantly higher in the mean provided energy of ≥30 kcal/IBW/day (kg) group (p = 0.004 and p < 0.001, respectively). A high provided energy for patients with sarcopenic dysphagia may improve swallowing ability and produce clinically meaningful functional outcomes.

Ideal Body Weight-Based Dosing of Rabbit Antithymocyte Globulin for Cost Minimization in Kidney Transplantation

2021 ◽  
pp. 152692482110032
Author(s):  
Rachel J. Bubik ◽  
Kristen T. Peterson ◽  
Laura J. Myhre ◽  
Stacy A. Bernard ◽  
Patrick Dean ◽  
...  
Keyword(s):  
Body Weight ◽  
Actual Body ◽  
Cost Savings ◽  
Ideal Body Weight ◽  
Actual Body Weight ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
Protocol Group ◽  
Ideal Body ◽  
The Mean

Introduction: Contemporary dosing strategies for rabbit anti-thymocyte globulin (rATG) in kidney transplantation aim to reduce cumulative exposure, minimizing long-term adverse events. The use of ideal body weight-based dosing has been trialed, however concern for increased rejection post-transplant exists due to lower doses of rATG. Research Questions: The primary aim of this study was to compare rejection rates between rATG dosing protocols using actual body weight and ideal body weight and secondarily to evaluate cost savings following protocol implementation. Design: This was a retrospective study surrounding implementation of an ideal body weight-based dosing protocol for rATG. We compared 75 kidney transplant recipients in whom rATG was dosed based on actual body weight (pre-protocol group) to 64 in whom dosing was based on ideal body weight (post-protocol group), following a nine-month washout. Results: The mean cumulative rATG dose in the pre-protocol group was 6.3 mg/kg of actual body weight. When ideal body weight was used in the post-protocol group, the mean dose was 4.5 mg/kg of actual body weight. The rejection rate was 18.7% pre-protocol and 23.4% postprotocol, which did not represent a statistically significant difference (p = 0.491). The actual annual cost savings after protocol implementation exceeded $162,000, approximately $2,500 per patient. Conclusion: Results suggest ideal body weight-based dosing of rATG may reduce exposure and cost, without significantly impacting the risk of rejection in kidney transplant recipients. More studies are needed to confirm these findings.

scholarly journals A Multicentre Study Investigating the Pharmacokinetics and Pharmacodynamics of Busulphan When Combined with Melphalan As Conditioning in Adult Autologous Transplant Recipients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2190-2190
Author(s):  
Abbey Willcox ◽  
Eric Wong ◽  
Ashish R Bajel ◽  
Simon J. Harrison ◽  
Rosemary Thurston Hoyt ◽  
...  
Keyword(s):  
Body Weight ◽  
Multivariate Analysis ◽  
Research Funding ◽  
Drug Exposure ◽  
Univariate Analysis ◽  
Ideal Body Weight ◽  
Time Curve ◽  
Ideal Body ◽  
The Mean ◽  
The Relationship

Abstract Busulfan (Bu) is an alkylating agent commonly used in conditioning regimens prior to allogeneic stem cell transplantation (SCT). Whilst systemic drug exposure is thought to be critical for efficacy and safety of this agent (Kletzel et al. 2006; Bartelink et al. 2009; Andersson et al. 2002), there is a paucity of pharmacokinetic (PK) and pharmacodynamic (PD) evidence-based guidelines outlining how best to balance these potentially competing outcomes. In this study Bu PK was investigated in the setting of IV Bu-melphalan (mel) autologous SCT, with the primary intention of establishing factors influencing Bu exposure and how effectively PK assessment can be used to achieve desirable drug exposure. PD analysis was also performed to establish the effect of drug exposure on transplant-related toxicity. Sixty-four adult patients with haematological malignancies were prospectively enrolled prior to IV Bu-mel autologous SCT. PK analysis was performed in all patients on a "test" dose of Bu (1.6mg/kg, ie. 50% of a therapeutic dose) on day-7 based on actual body weight (ABW) (n=38) or adjusted ideal body weight (AIBW; n=24) where AIBW (kg) = Ideal body weight + [0.25 x (ABW- IBW)]). All patients subsequently received a second 1.6mg/kg dose on day-6. Thereafter, 27 patients received a further three 'therapeutic' daily doses of 3.2mg/kg on days -5 to -3 irrespective of PK results whist the remaining 37 patients received a modified dose, guided by the results of the initial PK results, targeting a subsequent Bu exposure, expressed as the area-under-the-concentration-versus- time curve (AUC), between 4000-5000umol.min/day (4000 in 2, 4500 in 14, 4800 in 4 and 5000 umol.min/day in 17) the lower ranges targeted in older patients with less aggressive disease. All patients had repeat PK analysis on day-5. Pre−transplant factors including age, weight, body mass index (BMI) and renal function were evaluated for their effect on the relationship between Bu dose and AUC; a multivariate analysis was performed on all covariates that were significant (p<0.05) in a univariate analysis. The mean Bu dose for patients receiving PK-guided dosing was 3.4mg/kg (range 2.6-4.8 mg/kg) with the mean AUCs in the target groups of 4000-4500 and 4800-5000 umol.min/day being 4821 (3639-5457) and 5142 (4138-6157) umol.min/day respectively; the mean AUC for the non-adjusted-dose cohort was 4785umol.min/day (3251-6305umol.min/day); (p=0.16). All but one patient in the PK-guided group (36/37) vs 22/27 (81%) in the non-adjusted group (p=0.03) achieved AUCs within the 3500-6000umol.min/day range, which has been found to be safe and effective in previous studies (Clemmons et al. 2015). Of the five patients who did not achieve this target, 3 achieved AUCs below 3500umol.min/day and 2 greater than 6000umol.min/day. Day -5 dose adjustments (from 3.2mg/kg) were suggested for 92% (34/37) of eligible patients and implemented in 87% (32/37) patients. These consisted of a Bu dose less than 3.2mg/kg (2.6-3.1mg/kg) in 8 patients which resulted in a mean AUC 5182umol.min/day (3904-6157umol.min/day); 38% of these patients achieved their target AUC (+/-10%). Five patients received an unchanged Bu dose of 3.2mg/kg achieving a mean AUC of 4906umol.min/day (4302- 5717umol.min/day) of which two were within 10% of their target AUC. Twenty-four patients received an increase dose (3.3-4.8mg/kg) and achieved a mean 4954umol.min/day (3639-5890umol.min/day) 45% achieved their target AUC (+/-10%). The mean variance from the target was 11% (0-30%). Using ABW or AIBW did not impact on this variance (mean 10% vs 12% respectively). Doses were frequently reduced (51% in the dose-adjusted cohort, mean of 15%) from the suggested dose based on day-7 AUC as it was observed early that the mean day-5 AUCs, in both cohorts, were higher than anticipated for the dose prescribed (mean 11%, -22 - 31%). Multivariate analysis demonstrated actual weight as the only independent variable impacting the relationship between Bu dose and AUC; higher body weight was associated with lower AUCs (p=0.02) relative to Bu dose. No correlation between AUC and the occurrence of grade 3 or greater transplant related toxicities such as mucositis (based on number of days requiring total parental nutrition) or hepatotoxicity was observed. PK-directed Bu dosing may be of benefit in achieving a target level of drug exposure, but larger studies are needed to determine the clinical significance of this strategy. Disclosures Harrison: AbbVie: Research Funding; Janssen Cilag: Research Funding, Speakers Bureau.

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