Weight-based Dosing Protocol Research Articles

Real-world overall survival after alternative dosing for pembrolizumab in the treatment of non-small cell lung cancer: A nationwide retrospective cohort study with a non-inferiority primary objective

BackgroundHigh and increasing expenses on pembrolizumab ask for more cost-effective and sustainable treatment strategies to improve affordability of healthcare. Therefore, a part of the Dutch hospitals implemented an alternative, partially lower, weight-based dosing protocol for pembrolizumab. This provided the unique opportunity to compare the overall survival (OS) of the alternative pembrolizumab dosing protocol to standard dosing using a nationwide registry in non-small cell lung cancer (NSCLC) patients. MethodsThis is a retrospective cohort study with a non-inferiority primary objective. Forty hospitals in the Dutch Medication Audit and Dutch Lung Cancer Audit treated 1966 patients with NSCLC with first line pembrolizumab (mono- or combination therapy) between Jan 1st 2021, and Mar 31st, 2023. Alternative weight-based pembrolizumab dosing (100/150/200 mg Q3W or 200/300/400 mg Q6W) was administered to 604 patients, and 1362 patients received standard pembrolizumab dosing (200 mg Q3W or 400 mg Q6W). A Cox proportional hazard model with selected covariates was used to compare the OS between alternative and standard dosing protocols. The non-inferiority margin was set at a hazard ratio (HR) of 1.2 for OS. Non-inferiority is established by showing that the upper limit of the 95 % confidence interval (CI) of the HR of OS is smaller or equal to 1.2. ResultsDistribution of age (66.7 years +/-9.4), sex (45 % female) and treatment combinations were similar for both groups, comorbidity score was higher in the standard group. Median daily dose in the alternative dosing group was 22 % lower compared to the standard dosing group, 7.14 mg/day (interquartile range (IQR):5.48–8.04 mg/day) vs. 9.15 mg/day (IQR:8.33–9.52 mg/day), respectively. Alternative dosing was non-inferior to standard dosing regarding overall survival (adjusted HR 0.83, 95 %CI:0.69–1.003). ConclusionThis large, retrospective real-world analysis supports the hypothesis that the alternative, partially lower pembrolizumab dosing protocol in NSCLC maintains treatment effectiveness while reducing treatment costs.

A simple, high-throughput and validated LC-MS/MS method for the determination of azithromycin in human plasma and its application to a clinical pharmacokinetic study.

A sensitive, specific and rapid liquid chromatographic–tandem mass spectrometric (LC–MS/MS) method was developed and validated to quantify azithromycin concentrations in human plasma. Azithromycin (AZI) is the most common outpatient prescribed antibiotic in the US and clinical studies have demonstrated the efficacy and safety of AZI in many bacterial infections. To support a clinical study, we developed a high‐throughput LC–MS/MS method to process up to 250 samples per day to quantify AZI in human plasma. Samples were prepared by solid‐phase extraction. Separation was achieved with an ACE C18 column (2.1 × 100 mm, 1.7 μm) equipped with a C18 guard column. The mobile phase consisted of 0.1% formic acid and methanol–acetonitrile (1:1, v/v) at a flow rate of 0.25 ml/min. The ionization was optimized with positive electrospray source using multiple reaction monitoring transition, m/z 749.50 > 591.45 for AZI and m/z 754.50 > 596.45 for AZI‐d5. Extraction recoveries were approximately 90% for AZI. The assay was linear from 0.5 to 2,000 ng/ml and required only 100 μl of plasma with a total analysis time of 4.5 min. The method was successfully applied to pharmacokinetic studies of a weight‐based dosing protocol for AZI.

Correction of Anticoagulant Therapy in Patients with Severe COVID-19 Virus Infection Using a Thrombodynamics Coagulation Assay.

The average frequency of thrombosis in patients with COVID-19 is still high despite low molecular weight heparin (LMWH) prophylactic. Global hemostasis assays, particularly thrombodynamics (TD), known to be sensitive to both hypercoagulation and heparin effects, could potentially be useful for individual management of anticoagulant therapy. A total of 74 patients with lung involvement >50% were randomized into two groups: Group A (44 patients) received weight-based dosing of LMWH, and Group B (30 patients) received the first LMWH dose by a weight-based dosing protocol and then received an adjusted dose based on TD daily results. The endpoints of the study were thrombosis and bleeding as well as discharge or death of the patient. The incidence of thrombosis was 3 times lower in Group B under TD control compared to Group A without TD control: 7% versus 23 respectively (p = .05). The relative risk of thrombosis if the average clot growth rate V in TD exceeded the threshold value of 25 μm/min was 14.3 (p = .0005, 95% confidence interval 3.2-63.7). There were no clinically significant bleeding episodes in Group B while there were 7% in unregulated Group A. Mortality in Group B under TD control was lower than that in Group A without control: 27% versus 36%, respectively (p = .13). The dosing LMWH under thrombodynamics control in severe patients with COVID-19 allows for a significant reduction in thrombotic complications. Long-term hypercoagulation revealed by thrombodynamics (3 and more days) is a strong predictor of thrombosis (AUC = 0.83).

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

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. 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. 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. 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.

A Retrospective Comparison of 3-Factor Prothrombin Complex Concentrate Products for Warfarin Reversal.

Current guidelines suggest that 3-factor prothrombin complex concentrate is a possible alternative to 4-factor products for the emergent reversal of bleeding secondary to warfarin. While multiple observational studies have evaluated various forms of 3-factor prothrombin complex concentrate individually, no study has compared the efficacy of the 2 products. The purpose of this study is to compare the efficacy and safety of Bebulin™ and Profilnine™ for the emergent reversal of warfarin-associated major bleeding. We conducted a retrospective cohort study of patients receiving both Bebulin™ and Profilnine™ at an urban, academic medical center with comprehensive stroke center designation and a neurosurgical center of excellence. All patients were treated at a single center that utilized a fixed, weight-based dosing protocol. The primary outcome was the percentage of patients in each group achieving a goal international normalization ratio of 1.4 or less. There was a significant difference in goal international normalization ratio achieved favoring Bebulin™ (85.5% vs 27.3%; P < .001) over Profilnine™. Median dose per kilogram of actual body weight was the same between the groups. When we assessed results by baseline™ international normalization ratio subgroup, more patients in the Bebulin™ group achieved goal when baseline values were 6 or less. No thrombotic events were documented in either group. We found that patients treated with Bebulin™ experienced significantly higher rates of successful international normalization ratio reversal when compared to those who received Profilnine™. Further research is needed to determine the comparative efficacy between the 2 agents.

Adjusted vs Total Body Weight-Based Dosing of Sedation and Analgesia Used in the Intensive Care Unit.

Background: The purpose of this study was to evaluate if dosing fentanyl, dexmedetomidine, and propofol based on ideal or adjusted vs actual weight in patients would decrease overall opioid and sedative use. Methods: This was a retrospective chart review comparing adjusted vs actual weight-based dosing protocol of mechanically ventilated (MV) intensive care unit (ICU) adult patients who required fentanyl and either propofol or dexmedetomidine. Results: A total of 261 patients were included in which 101 patients were in the actual weight group and 160 patients were in the adjusted weight group. Total doses per MV day of fentanyl was 1042 ± 1060 µg in the actual weight group vs 901 ± 1025 µg in the adjusted weight group (P = .13). Total doses per MV day of midazolam was 20 ± 19 mg in the actual group vs 15 ± 19 mg adjusted group (P = .02). Average MV days was 8.2 vs 7.1 days, ICU length of stay was 10.6 vs 9.4 days, and self-extubation rates were 17.8% vs 4.4% in the actual group and adjusted group, respectively. Conclusion: Total midazolam doses per MV day were lower in the adjusted group. No significant change was seen in MV days, ICU length of stay, or self-extubation rates.

Cefazolin Prophylaxis for Total Joint Arthroplasty: Obese Patients Are Frequently Underdosed and at Increased Risk of Periprosthetic Joint Infection

BackgroundOne of the most effective prophylactic strategies against periprosthetic joint infection (PJI) is administration of perioperative antibiotics. Many orthopedic surgeons are unaware of the weight-based dosing protocol for cefazolin. This study aimed at elucidating what proportion of patients receiving cefazolin prophylaxis are underdosed and whether this increases the risk of PJI. MethodsA retrospective study of 17,393 primary total joint arthroplasties receiving cefazolin as perioperative prophylaxis from 2005 to 2017 was performed. Patients were stratified into 2 groups (underdosed and adequately dosed) based on patient weight and antibiotic dosage. Patients who developed PJI within 1 year following index procedure were identified. A bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify risk factors for PJI. ResultsThe majority of patients weighing greater than 120 kg (95.9%, 944/984) were underdosed. Underdosed patients had a higher rate of PJI at 1 year compared with adequately dosed patients (1.51% vs 0.86%, P = .002). Patients weighing greater than 120 kg had higher 1-year PJI rate than patients weighing less than 120 kg (3.25% vs 0.83%, P < .001). Patients who were underdosed (odds ratio, 1.665; P = .006) with greater comorbidities (odds ratio, 1.259; P < .001) were more likely to develop PJI at 1 year. ConclusionCefazolin underdosing is common, especially for patients weighing more than 120 kg. Our study reports that underdosed patients were more likely to develop PJI. Orthopedic surgeons should pay attention to the weight-based dosing of antibiotics in the perioperative period to avoid increasing risk of PJI.

Comparison between a fixed-dose contrast protocol and a weight-based contrast dosing protocol in abdominal CT

To compare a fixed-dose intravenous iodinated contrast medium protocol with weight-based dosing protocols for abdominal computed tomography (CT). Fifty patients were scanned using a fixed-dose protocol, 50 patients were scanned using a full-dose weight-based contrast dosing protocol, and 13 patients were scanned using a reduced dose weight-based protocol. Radiodensity was measured at the portal vein, aorta, spleen, and liver. These values were plotted against contrast medium dose per unit weight. Images from all patients were anonymised and presented to two independent consultants who subjectively assessed contrast enhancement using a five-point Likert scale. Using a fixed-dose protocol, there was a statistically significant negative correlation and trend between patient weight and radiodensity at the portal vein, aorta, spleen, and liver. Using a full-dose weight-based contrast dosing protocol, there was no longer a statistically significant correlation or trend implying a more consistent degree of enhancement over a spectrum of patient weights. In addition, when the full-dose weight-based contrast dosing protocol was used, there was a statistically significant increase in the number of scans subjectively assessed as having ideal enhancement and a statistically significant decrease in the number of scans felt to have excessive enhancement when compared to a fixed-dose protocol. The weight-based dosing protocol used less contrast medium than the fixed-dose protocol and there was no evidence of contrast-induced acute kidney injury (CIAKI) in any of the patients that received a greater dose than that which they would have received using a fixed-dose protocol. The reduced-dose weight-based protocol showed less objective enhancement of the portal vein, abdominal aorta, spleen, and liver compared to the full-dose protocol and a reduction in the number of scans perceived as showing ideal enhancement. There was, however, no increase in the number of scans with poor or non-diagnostic enhancement. Weight-based contrast medium dosing has been shown to objectively provide more consistent vessel and solid-organ enhancement and subjectively improve image quality across a spectrum of weights. Depending on mean patient mass, it has also been shown to reduce overall contrast medium dose, and there is no evidence of CIAKI in patients that receive larger doses. This study also postulates that a standardised approach to contrast medium dose reduction in patients with renal impairment may be a viable strategy.

Peak cortisol response to corticotropin-releasing hormone is associated with age and body size in children referred for clinical testing: a retrospective review.

BackgroundCorticotropin-Releasing Hormone (CRH) testing is used to evaluate suspected adrenocorticotropic hormone (ACTH) deficiency, but the clinical characteristics that affect response in young children are incompletely understood. Our objective was to determine the effect of age and body size on cortisol response to CRH in children at risk for ACTH deficiency referred for clinical testing.MethodsRetrospective, observational study of 297 children, ages 30 days – 18 years, undergoing initial, clinically indicated outpatient CRH stimulation testing at a tertiary referral center. All subjects received 1mcg/kg corticorelin per institutional protocol. Serial, timed ACTH and cortisol measurements were obtained. Patient demographic and clinical factors were abstracted from the medical record. Patients without full recorded anthropometric data, pubertal assessment, ACTH measurements, or clear indication for testing were excluded (number remaining = 222). Outcomes of interest were maximum cortisol after stimulation (peak) and cortisol rise from baseline (delta). Bivariable and multivariable linear regression analyses were used to assess the effects of age and size (weight, height, body mass index (BMI), body surface area (BSA), BMI z-score, and height z-score) on cortisol response while accounting for clinical covariates including sex, race/ethnicity, pubertal status, indication for testing, and time of testing.ResultsSubjects were 27 % female, with mean age of 8.9 years (SD 4.5); 75 % were pre-pubertal. Mean peak cortisol was 609.2 nmol/L (SD 213.0); mean delta cortisol was 404.2 nmol/L (SD 200.2). In separate multivariable models, weight, height, BSA and height z-score each remained independently negatively associated (p < 0.05) with peak and delta cortisol, controlling for indication of testing, baseline cortisol, and peak or delta ACTH, respectively. Age was negatively associated with peak but not delta cortisol in multivariable analysis.ConclusionsDespite the use of a weight-based dosing protocol, both peak and delta cortisol response to CRH are negatively associated with several measures of body size in children referred for clinical testing, raising the question of whether alternate CRH dosing strategies or age- or size-based thresholds for adequate cortisol response should be considered in pediatric patients, or, alternatively, whether this finding reflects practice patterns followed when referring children for clinical testing.Electronic supplementary materialThe online version of this article (doi:10.1186/s13633-015-0018-y) contains supplementary material, which is available to authorized users.

Effect of Body Weight on Cefazolin and Vancomycin Trabecular Bone Concentrations in Patients Undergoing Total Joint Arthroplasty

Effective use of prophylactic antibiotics decreases the incidence of surgical site infections (SSIs) after total joint arthroplasty (TJA). The purpose of this prospective study was to determine the viability of weight-based dosing protocols for cefazolin and vancomycin to determine if appropriate minimum inhibitory concentrations (MIC) are met. Trabecular bone was harvested from discarded bone samples from 34 patients undergoing total knee arthroplasty (TKA) and total hip arthroplasty (THA). The cefazolin and vancomycin concentrations were determined in the trabecular bone using high-performance liquid chromatography. No difference was noted in bone concentration with respect to patient weight for cefazolin. Regarding vancomycin, a substantial difference was noted in trabecular bone concentrations with respect to patient weight with lower body mass index (BMI) achieving greater concentrations. Using the current weight-based protocol of antibiotic prophylaxis, 84% and 87% of patients receiving vancomycin and cefazolin, respectively, achieved bone concentrations above the MIC. Our assessment of trabecular concentration of cefazolin during TJA did not show any differences with respect to patient weight. However, vancomycin concentrations did show a difference with respect to BMI but this may be the result of the specific weight-based dosing protocol of vancomycin. Whereas the majority of cases were able to achieve adequate antibiotic concentrations in bone, further studies may be required to determine if increasing the pre-operative dosage of antibiotics is mandated given the findings of this pilot study.

Efficacy and safety of Prothrombin Complex Concentrates Weight-Based Dosing for Reversal of Warfarin Anticoagulation

▪Background: Prothrombin complex concentrates (PCCs) are widely used for correcting elevated international normalized ratio (INR) levels in patients anticoagulated with warfarin requiring an urgent reversal. However, the optimal dosing regimen has yet to be defined. In 2008, the Canadian National Advisory Committee (NAC) on blood product utilization recommended a single dose of 1000 IU for all adults over 18 years of age, irrespective of INR levels, and suggested further consultation with a Hematologist if extremes in weight or INR were observed. A revision in 2011, suggested dosing based on the INR elevation as an option and in 2014 the recommendation was updated to include a possible algorithm including both INR and weight. Currently there is insufficient evidence to suggest that one approach is more efficacious than another. Our institution has been using a novel weight-based dosing protocol for PCCs since 2009, which dispenses to a maximum of 3000 IU for adults weighing over 100kg. Herein, we sought to determine the efficacy of our weight-based dosing nomogram.Methods: We conducted a retrospective cohort study of all consecutive adult patients (age > 18 years) who received PCCs using our weight based dosing regimen between April 30, 2009 and December 31, 2010. All patients were anticoagulated with warfarin. Clinical and laboratory information was obtained through chart review. The weight based regimen consisted of 1000 IU for weight less than 40kg, 1500IU for 41 to 60kg, 2000 IU for 61 to 80kg, 2500 IU for 81 to 100kg, and 3000 IU for > 100kg. Doses of PCCs were based on the concentration of factor IX. PCCs utilized at this centre were Octaplex and Beriplex. The primary outcome was reversal of warfarin anticoagulation, as defined by an INR of 1.5 or less to achieve a clinical response within 6 hours. Statistical analysis was done using descriptive statistics and chi squared analysis.Results: A total of 227 charts were included in the study from April 30, 2009 to December 31, 2010. The median age was 74 years old (range 40-95), the median weight was 76kg (range 44-200), and 56% of patients were male. Medical indications for warfarin anticoagulation included atrial fibrillation (68%), DVT (32%) and stroke (21%). The most common indication for PCCs was active bleeding (44%: 13% intracranial, 12% gastrointestinal, 4% trauma, 15% other), reversal for a procedure (22%) and reversal for surgery (30%). Prior to receiving PCCs, 29% of patients were taking Aspirin and 4% were taking Clopidogrel. The percentages of patients treated with each dose were: 1000IU (1.3%), 1500IU (17.6%), 2000IU (41.0%), 2500IU (24.2%), 3000IU (15.9%). A second dose of PCC was given to 0.4% of patients. FFP was given to 7% of patients prior to PCCs administration and 14% of patients post PCCs administration. 63% of patients received vitamin K. Seventy-nine percent of patients achieved an INR of 1.5 or less within 6 hours of PCC administration. There was a statistically significant difference in response based on pre-PCC INRs (see table 1). The median baseline INR was 2.9 (range 1.5- >10) and decreased to a median of 1.3 (range 1.0-3.7) post-PCCs administration. Planned procedures were completed in 93% of 60 patients, and planned surgeries were completed in 94% of 70 patients within 24 hours of receiving PCCs. Four patients (2%) developed a deep vein thrombosis within 30 days of receiving PCCs.Conclusion: Our study demonstrates that weight based dosing is effective in reversal of anticoagulation in patients on warfarin. Laboratory response rates are similar to other studies (Wozniak et al). Although the majority of patients in our study (99%) received doses over 1000IU; rates of thrombosis are low. Future studies comparing different strategies are needed.Table 1INR rangePre-PCCProportion with Post-PCC INR of 1.5 or less (%)P-value1.5-3110/122 (90%)3.1-4.533/43 (77%)0.037*>4.535/62 (56%)<0.001***1.5-3 vs 3.1-4.5**1.5-3 vs >4.5 DisclosuresLazo-Langner:Pfizer Bayer LEO Pharma: Honoraria. Chin-Yee:Alexion Pharmaceuticals: Research Funding.

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Introduction: Anticoagulation with warfarin is associated with numerous adverse events and complications, the most significant being intracranial hemorrhage (ICH). Prothrombin complex concentrate (PCC) is recommended for international normalization ratio (INR) reversal, however data regarding its use following ICH is variable with regards to dosing, infusion rate, and product choice. Available evidence supports efficacy of 4-factor PCC when compared to fresh frozen plasma (FFP), yet there are no direct comparisons with 3-factor products. Methods: We conducted a retrospective chart review of all patients receiving 3-factor PCC for reversal of INR following ICH between the dates of January 1, 2012 and August 1, 2013. Patients were excluded if they received PCC for an alternate indication or did not have an available baseline and/or repeat INR following PCC administration. Results: A total of 36 patients were included, one half of which were female. On presentation, the median age was 69 years and the mean INR was 4.1 ± 1.0. Thirty-three of 36 patients (91.7%) achieved an initial goal INR (≤ 1.4) following a single PCC dose, with the mean INR after PCC infusion being 1.2 ± 0.2. The average dose of PCC given after rounding to the nearest vial size was 31 IU/kg. Median time from PCC infusion to INR was 49 minutes. Vitamin K was utilized in 34 (94.4%) patients while FFP was given to only 5 (13.9%). In those with a baseline INR greater than 4.5, there was no difference in the probability of INR reversal, with 8 of 9 patients reaching goal INR after a single dose per our protocol (p<0.99). No patient experienced a documented thrombotic event within 7 days of PCC administration. PCC was infused over a median duration of 14 minutes (198 IU/minute) without any documented infusion reactions. Conclusions: Implementation of a fixed weight-based dosing protocol for 3-factor PCC was effective at providing rapid and complete INR reversal without any adverse events. With the new FDA approval of 4-factor PCC, 3-factor PCC may offer significant cost savings with similar efficacy however direct comparisons are needed.

Implementation of an Enoxaparin Protocol for Venous Thromboembolism Prophylaxis in Obese Surgical Intensive Care Unit Patients

Venous thromboembolism (VTE) is a serious health care issue that affects a large number of people. Few standards exist for delineating the optimal dosing strategy for VTE prevention in obese patients, especially in the setting of major surgery or trauma. To document the efficacy of a surgical intensive care unit (SICU)-specific, weight-based dosing protocol of enoxaparin 0.5 mg/kg given subcutaneously every 12 hours for VTE prophylaxis in morbidly obese (defined as body mass index [BMI] ≥35 kg/m(2) or weight ≥150 kg) SICU patients, using peak anti-factor Xa levels to determine therapeutic endpoints. Data were collected retrospectively in an academic, university-based SICU on 23 morbidly obese patients who received weight-based enoxaparin for VTE prophylaxis from December 1, 2008, through June 30, 2010. A weight-based dosage range of enoxaparin 50-120 mg twice daily (median 60) was given to 23 patients. The mean BMI was 46.4 kg/m(2). The initial mean anti-factor Xa level (measured after the third dose) was 0.34 IU/mL (range 0.20-0.59). Patients received an average of 18 doses. Two cases required an increase or decrease in dosage based on anti-factor Xa levels. Morbidity related to this dosing included a single event of minor endotracheal bleeding and a single deep vein thrombosis that was likely present prior to treatment. Weight-based dosing with enoxaparin in morbidly obese SICU patients was effective in achieving anti-factor Xa levels within the appropriate prophylactic range. This regimen reduced the rate of VTE below expected levels and no additional adverse effects were reported.

Weight-based heparin protocol using antifactor Xa monitoring

The performance of a weight-based dosing protocol for unfractionated heparin (UFH) infusions using antifactor Xa monitoring was evaluated. The first 50 patients to receive a UFH infusion per the new protocol for over 24 hours, regardless of indication, were included in the analysis. All patients received a bolus dose of 26 units/kg, followed by an i.v. infusion of 15 units/kg/ hr based on actual body weight, with no maximum dosage. Antifactor Xa levels were measured every 6 hours after infusion initiation and after every rate change until stable, defined as two consecutive results within the target range of 0.3-0.7 unit/mL, and every 24 hours thereafter. If a level was outside of the target range, the infusion rate was adjusted. Primary outcomes measured included the percentage of patients with a target level at the first test (obtained 6 hours after the start of therapy) and within the first 24 hours. The success of the protocol in obese patients versus nonobese patients was also analyzed. Of the 50 patients enrolled, 26 (52%) achieved a target antifactor Xa concentration 6 hours after infusion initiation. Only 4 patients did not have an antifactor Xa concentration in the target range within 24 hours. Of the 17 patients weighing more than 100 kg, 16 (94%) had a value within the target range within 24 hours. A weight-based UFH dosing nomogram using antifactor Xa monitoring resulted in a high percentage of patients achieving target antifactor Xa values within the first 24 hours of therapy.

A Study of a Weight-Adjusted Aprotinin Dosing Schedule During Cardiac Surgery

Aprotinin is effective during cardiac surgery for reducing blood loss and transfusion requirements, but it is expensive. Aprotinin is usually administered to adults according to a fixed protocol regardless of the patient’s weight. We previously developed a weight-based dosing protocol for aprotinin. The purpose of this prospective observational study was to determine aprotinin levels in four patient groups (n = 10 each) using the new weight-based aprotinin dosing schedule that should achieve concentrations over 100, 150, 200, and 250 kallikrein inhibitory units/mL compared with full-dose aprotinin regimen (n = 10) by a simple functional aprotinin assay. There was no difference in patient demographic or surgical variables among groups. There was less within patient variation in plasma aprotinin concentrations over time in the new weight-based aprotinin dosing schedule groups compared with the full-dose aprotinin regimen group (P < 0.02 for all comparisons). The mean plasma aprotinin concentration achieved with the new weight-based aprotinin dosing schedule was similar to the desired concentrations, but we were unable to reduce between-patient variability in aprotinin concentrations.

Increased extra-cardiac background uptake on immediate and delayed post-stress images with 99Tcm sestamibi: determinants, independence, and significance of counts in lung, abdomen and myocardium.

Extra-cardiac activity on stress scans with 99Tcm sestamibi (MIBI) may influence scan interpretation. Lung uptake represents a potential sign of severe disease, whereas abdominal uptake may interfere with visualization of myocardial defects. We assessed myocardial, lung and infradiaphragmatic abdominal activity on images at 4 min (IMM) and 1 h (DEL) post-stress in 1800 consecutive studies. Potential variation among patients in organ activity was reduced with a weight-based dosing protocol. Multifactorial analysis was used to compare organ activity, and background ratios, i.e lung/heart or abdomen/heart, on stress images to (1) result of tomography, (2) peak workload, and (3) protocol (same-day versus separate-day rest/stress). Lung/heart ratios were primarily related to tomographic abnormalities, and abdomen/heart ratios to low stress workload; neither was related to protocol, and the two measurements appeared independent. Elevated lung/heart ratios (compared to angiographic normals), present on 16% and 10% of IMM and DEL images respectively, were determined primarily by increases in regional lung activity. Lung activity (normalized for dose) was higher in cases with disease than in normals (P<0.0001 as assessed by tomography, P<0.05 in the subset with correlating angiography). Increased abdominal/heart ratios derived primarily from increased abdominal activity, but were partially dependent on reciprocal decreases in myocardial activity. Elevated MIBI lung uptake ratios on abnormal scans can be attributed primarily to increased lung persistence of the radiotracer, and would thus be consistent with their use as a sign of left ventricular failure. Elevated abdominal background is associated with both higher splanchnic activity and lower myocardial activity, and is a non-specific finding related to suboptimal exercise intensity.