Weight-based Protocol Research Articles

Exploring Emergency Department Provider Experiences With and Perceptions of Weight-Based Versus Individualized Vaso-Occlusive Treatment Protocols in Sickle Cell Disease.

Treatment of vaso-occlusive episodes (VOEs) is the most common reason for emergency department (ED) treatment of sickle cell disease (SCD). We (1) compared perceptions of the usability and ability to manage VOE pain between ED nurses and other ED provider types, ED sites, and VOE protocols (individualized vs. weight-based), and (2) identified ED nurse and other provider protocol suggestions. A secondary analysis of provider survey data collected immediately after caring for a patient enrolled in a randomized controlled trial comparing weight-based versus individualized opioid dosing for VOE. Research staff asked the ED nurses and other ED providers (nurse practitioners [NPs], physician assistants [PAs], residents, and attending physicians) 5 questions related to the protocol's ease of use and ability to manage pain. There were 236 surveys completed. Attending physicians (n = 15), residents (n = 88), PAs (n = 21), and NPs (n = l) were more satisfied than nurses (n = 111) with the clarity of the analgesic ordering (97.6% vs. 0%, p = 0.0001) and ability to manage the patient's VOE pain (91% vs. 0%, p = 0.0001). When comparing both protocols with the usual ED strategy in their ED to manage VOE, more nurses than other ED providers perceived the study patients' pain management protocol as better (100% vs. 35.2%, p = 0.0001). Other ED providers perceived the individualized versus weight-based protocol as better at managing pain than their usual ED strategy (70.3% vs. 59.5%, p = 0.04). The individualized protocol was perceived as better in managing VOE than the weight-based ED strategy. While physicians were satisfied with the clarity of the protocols, nurses were not. Improved protocol usability is required for widespread ED implementation.

Body Weight-Based Protocols During Whole Body FDG PET/CT Significantly Reduces Radiation Dose without Compromising Image Quality:Findings in a Large Cohort Study

To investigate radiation dose reduction during whole body fluorodeoxyglucose (18F-FDG) positron emission tomographic (PET)/computed tomography (CT) by employing weight-based protocols. One thousand and twenty-eight patients were referred for 18F-FDG PET/CT study with one of two protocols: conventional protocol I; 120 kVp, 120 mAs, 0.5 second rotation time, pitch 0.8 mm/rot across all body weights; four-tier body weight protocol II all used 140 kVp, 0.75 seconds rotation time and pitch 0.8 mm/rot: Protocol A (≤60 kg): 35 mAs, Protocol B (61-80 kg): 50 mAs, Protocol C (81-100 kg): 65 mAs, and Protocol D: (>101 kg): 100 mAs. All protocols employed tube current modulation. Quantitative and qualitative image visual grading characteristics assessed image quality. Patient demographics demonstrated no significant difference between each protocol except for patient weight in weight protocol IIB (p < 0.009). Mean effective dose in all protocols were significantly lower in Protocol B compared to A (p < 0.009). Contrast-to-noise ratio demonstrated no differences between each protocol (p < 0.21) except for weight protocol in protocol IIA (<60 kg, p = 0.035) with the visual grading characteristics demonstrating preference over protocol II compared to I. Significant reduction in radiation dose can be achieved using patient-specific body weight-based protocols during whole-body 18F-FDG PET/CT without compromising image quality when employing weight-based protocols.

Reduction of Blood Loss by Tranexamic Acid Following Total Hip and Knee Arthroplasty: A Meta-Analysis.

This study involved a meta-analysis of 36 published studies to examine the efficacy of intravenous (IV) and intra-articular (IA) tranexamic acid (TXA) in reducing blood loss, drain output, thromboembolic complications, and hospital stay following total hip and total knee arthroplasty. This study also evaluated whether treatment with a combination of both IA and IV TXA has an effect on these outcomes. Lastly, this study attempted to analyze the method and technique of TXA administration in order to establish a best practice for its use in reducing overall blood loss in arthroplasty procedures. MEDLINE, Embase, and the Cochrane Library database were screened. Studies comparing IV TXA with IA TXA or with combined IV and IA TXA were included. Data including total blood loss, drain output, thromboembolic complications, and hospital stay, where available, were analyzed using meta-analysis with fixed effects. Results are presented as the standardized mean difference (SMD), and meta-regression was employed to explore plausible demographic contributions to heterogeneity. Twenty-eight randomized controlled trials, 3 prospective cohort studies, and 5 retrospective cohort studies with 5,499 patients were included in this review. IA administration during total knee arthroplasty showed a significant advantage in terms of total blood loss (SMD = -0.14, 95% confidence interval [CI] = -0.027 to -0.02, I = 78.2%) and drain output (SMD = -0.30, 95% CI = -0.43 to -0.18). There was no significant difference between IV and IA administration in total hip arthroplasty. Combined IA plus IV TXA was associated with a significant reduction in blood loss versus IV TXA alone in both total knee arthroplasty and total hip arthroplasty. IV TXA dosing varied, as 14 (39%) of the studies used a weight-based approach while 22 (61%) used a standard dose. Twenty-seven (96%) of 28 studies of IA administration used standard dosing while 1 study followed a weight-based protocol. There was no difference in symptomatic thromboembolic complications, with overall rates in total knee arthroplasty and total hip arthroplasty of 1.0% and 1.0% for IV administration and 1.1% and 0.3% for IA administration, respectively. There was no difference in length of hospital stay for IV versus IA TXA administration. IA TXA, either alone or in conjunction with IV TXA, reduces total blood loss and/or drain output in total knee arthroplasty and total hip arthroplasty. Optimal methodology remains to be clarified; however, there are substantial economic benefits of utilizing either IV or IA TXA, with greater cost benefits when using IA TXA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Assessing the Effect of Weight-Based Protocol Modifications to Lower Dose for CT-Guided Hepatic and Renal Tumor Radiofrequency Ablations.

This study assessed radiation dose after CT-guided percutaneous radiofrequency ablations (RFAs) of hepatic and renal tumors and the effect of weight-based CT protocol modification for lowering overall dose in these procedures. CT-guided RFA for renal and hepatic ablations performed from January 1, 2009, through December 31, 2009, were retrospectively reviewed (90 men and 48 women; age, 42-81 years). The radiation dose was recorded during each of the following steps: planning, performing, and postprocedure. Weight-based protocol modification changes in tube voltage and tube current were then applied to renal and hepatic ablations performed subsequently (18 men and 11 women; age, 48-82 years). Image quality, needle localization, lesion detection, ability to detect complications, and overall operator satisfaction were noted for each case (score, 1-5). Dose reduction after modification was then calculated. Retrospective analysis found a mean (± SD) overall CT dose index (CTDI) for CT-guided RFA to be 16.5 ± 2.3 mGy. After protocol modification, the mean CTDI decreased to 6.63 ± 0.67 mGy, a 59.6% reduction overall; for hepatic ablations, the reduction was 65.96% (p < 0.0001) and the reduction for renal ablations was 38.97% (p = 0.0153). Image quality analysis showed high operator satisfaction (3-5), including adequate needle localization (4-5), lesion visibility (3-5), and high performer confidence (4-5). Higher dose reduction was noted for patients weighing more than 180 lb (82 kg) (p < 0.0001). Simple weight-based CT protocol modifications can significantly reduce radiation dose during CT-guided percutaneous ablations in the liver and kidneys without significantly sacrificing image quality.

Severely prolonged vancomycin half-life in a patient with normal serum creatinine and creatinine clearance

Vancomycin remains the antibiotic of choice to treat resistant Gram-positive infections and is dosed utilizing weight-based protocols or pharmacokinetic calculations. Pharmacokinetic calculations are a more proactive approach to vancomycin dosing but are occasionally limited as certain patient-specific variables such as volume of distribution, renal function, and severity of illness do not allow all patients to follow population estimates. In these situations, if the above-mentioned variables are adjusted for an individual patient rather than the population estimates, the kinetic models reflect accurate vancomycin dosing. We present a patient with apparently normal renal function (Cockcroft–Gault) following a significant renal injury who had sustained supratherapeutic vancomycin serum concentrations and a calculated peak elimination half-life of 346 h. Importantly, this patient had adequate clearance of other highly renally eliminated medications (digoxin and meropenem), which suggests limited long-term deficit due to the previous sustained renal injury. In this patient case, vancomycin's chemical properties and pharmacokinetics are explored to best explain the patient's highly unusual response. In addition, an analysis of vancomycin's less well-described pharmacokinetics such as active secretion, tubular reabsorption, and nonrenal elimination pathways is explored. Ultimately, this patient represents a perplexing case which highlights the continued need for therapeutic drug monitoring with vancomycin.

The management of peri- and postprocedural pain in interventional radiology: a narrative review.

Interventional radiology encompasses a wide range of procedures and the degree of associated pain depends predominantly on the procedure being undertaken. Procedures may be painful during but not after the procedure, relatively painless during but painful after the procedure, or relatively painless during and after the procedure. However, there is a lack of good quality publications in interventional radiology that specifically address the subject of peri- and postprocedural pain management. Nevertheless, a variety of more or less complex protocols exist for intraprocedural sedation and for peri- and postprocedural analgesia. While weight-based protocols for procedural sedation have demonstrable benefit, protocols for postprocedural pain relief after major procedures have not been sufficiently rigorously evaluated.

Valganciclovir Dosing for Cytomegalovirus Prophylaxis in Pediatric Solid-organ Transplant Recipients

Valganciclovir is extensively used for prophylaxis and treatment of cytomegalovirus (CMV) infection in solid-organ transplant recipients. However, pharmacokinetic data in children are scarce, and the pediatric dosing regimen is uncertain. This study sought to prospectively evaluate the pharmacokinetic profile, the clinical efficacy and safety of oral valganciclovir in pediatric transplant recipients and compare different dosing regimens. The cohort included solid-organ transplant recipients treated with valganciclovir for CMV prophylaxis in 2014-2015 at a tertiary pediatric medical center. All received a weight-based once-daily oral dose of 17 mg/kg. Ganciclovir concentrations were measured and the area under the curve (AUC0-24) was calculated. Thirteen children of median age 7.3 years (interquartile range, 2.2-11.6) were included. Median ganciclovir AUC0-24 was 21.0 mcg·h/mL (interquartile range, 17.1-39.8); 10 patients (77%) attained AUC0-24 <40 mcg·h/mL. Exposure to ganciclovir was about 2-fold lower in young children (<9 years old; P = 0.01) and children with low body surface area (BSA; <0.7 m; P = 0.006) than in their counterparts. Significantly lower doses were recommended with our weight-based protocol than with the manufacturer-recommended BSA- and glomerular filtration rate-based protocol (P = 0.002), reaching a 3-fold difference in infants. No evidence of CMV viremia or disease was observed while prophylaxis was given. The weight-based regimen of 17 mg/kg/dose oral valganciclovir results in relatively low ganciclovir exposure, especially in young children with low BSA, yet showed satisfactory clinical efficacy for CMV prophylaxis. The manufacturer's dosing recommendation appears to result in supratherapeutic ganciclovir concentrations. Further studies are needed to establish target AUCs and valganciclovir dosing for CMV prophylaxis in pediatric transplant recipients.

Bone penetrance of locally administered vancomycin powder in a rat femur fracture model

IntroductionLocally delivered, crystalline vancomycin has been suggested as a potential prophylactic measure against the development of deep and superficial surgical site infection. Clinical expectations regarding the duration and peak of drug concentration in local tissues following administration are unknown. Our goal was to develop concentration vs time curves for locally administered vancomycin powder in a high-energy, open femur fracture rat model in local tissues and to compare that data to two well performed similar, systemic administration studies. MethodsAfter approval for animal research, 24 adult Sprague-Dawley rats sustained closed, midshaft femoral fracture under anesthesia. Fractures were caused via blunt guillotine with 750g metal rod dropped 50cm. Injured hindlimbs were surgically opened at fracture to simulate open injury and stabilized using 0.054 Kirschner wires. Vancomycin powder was administered using weight-based protocol (goal: 25mg/kg). Rats were sacrificed in groups of 4 at 4, 8, 24, 48, 72, 96h. Samples harvested included rat-tail venous blood prior to sacrifice, and femoral bone and anterior thigh soft-tissue were harvested post-mortem. High Performance Liquid Chromatography (HPLC) was performed on all samples. ResultsConcentration vs. time curves demonstrated that the surrounding soft-tissues demonstrated highest maximum concentration (1.5mg vancomycin/g muscle). Bone reached maximum average of 199μg vancomycin/g femur: approximately 13% of maximal soft-tissue absorption. Plasma reached maximum concentration of 1.8μg/mL plasma. All peaks at t=4h. Within 48h, average muscle vancomycin concentration dropped to 3μg/g muscle (0.2% maximum muscle concentration) and the average bone concentration dropped to 1.9μg/g femur (0.9% maximum bone concentration). Vancomycin was undetectable on all samples at 96h. Comparison to classical animal studies suggest local delivery to bone exceeds that of IV dosing for approximately 48h and may peak near concentrations of 102 multiples. ConclusionsLocally administered vancomycin provides drug delivery in excess of IV dosing for approximately 48h after intervention. Exponential decay demonstrates rapid removal of drug to near undetectable levels in bone, plasma, and local soft tissue thereafter in a rat model. Local delivery may generate concentrations exceeding that achievable by steady state systemic dosing for 48h.

Vancomycin Prophylaxis for Total Joint Arthroplasty: Incorrectly Dosed and Has a Higher Rate of Periprosthetic Infection Than Cefazolin.

In total joint arthroplasty (TJA), vancomycin is used as perioperative antibiotic prophylaxis in patients with penicillin allergy or in patients colonized with methicillin-resistant Staphylococcus aureus (MRSA). Although vancomycin dosing should be weight-based (15mg/kg), not all surgeons are aware of this; a fixed 1-g dose is instead frequently administered. (1) Is there a difference in the risk of periprosthetic joint infection (PJI) in patients receiving vancomycin or cefazolin prophylaxis after primary TJA? (2) What proportion of patients is adequately dosed with vancomycin? (3) Compared with actual fixed dosing, does weight-based dosing result in a greater proportion of patients staying above the recommended 15-mg/L level at the beginning and end of surgery? (4) Are patients overdosed with vancomycin at greater risk of developing nephrotoxicity and acute kidney injury? A single-institution, retrospective study was performed on 1828 patients undergoing primary TJAs who received vancomycin prophylaxis between 2008 and 2014. During the same period, 5810 patients underwent primary TJA and received cefazolin monotherapy. A chart review was performed to obtain patient characteristics, antibiotic dose and timing of administration, and microbiology data. Adequate vancomycin dosing was defined as 15mg/kg and within the 125-mg range. Vancomycin levels were calculated at the beginning and end of surgery using pharmacokinetic equations. Levels of 15mg/L were considered adequate. Logistic regression, chi square tests, and analysis of variance were performed. Among primary TJAs, patients receiving vancomycin had a higher rate of PJI (32 of 1828 [2%]) compared with patients receiving cefazolin prophylaxis (62 of 5810 [1%]; adjusted odds ratio, 1.587 [1.004-2.508]; p=0.048). Ten percent of PJIs in the vancomycin underdosed group (two of 20) was caused by MRSA, and no patients with adequate dosing or overdosing of vancomycin developed PJI with MRSA. Of all procedures in which vancomycin monotherapy was used, 28% (518 of 1828) was adequately dosed according to weight-based dosage recommendations. Furthermore, 94% (1726 of 1828) of patients received a fixed 1-g dose of vancomycin, of whom 64% (1105 of 1726) were underdosed. All patients had vancomycin infusion initiated within 2 hours before incision. A weight-based protocol would have resulted in fewer patients having unacceptably low vancomycin levels (<15mg/L) compared with those with actual fixed dosing, both for the beginning of surgery at the time of incision (zero of 1828 [0%] versus 471 of 1828 [26%]; odds ratio, 0.001 [0.000-0.013]; p<0.001) and at the end of surgery (33 of 1828 [2%] versus 746 of 1828 [41%]; odds ratio, 0.027 [0.019-0.038]; p<0.001). Between the vancomycin dosage groups, there were no differences in the rate of nephrotoxicity (underdosed: 12 of 1130 [1%], adequately dosed: five of 518 [1%], overdosed: four of 180 [2%], p=0.363) and acute kidney injury (underdosed: 28 of 1130 [2%], adequately dosed: 10 of 518 [2%], overdosed: six of 180 [3%], p=0.561). The majority of patients given vancomycin prophylaxis are underdosed according to the weight-based dosage recommendations, and MRSA did not occur in patients who were adequately dosed with vancomycin. Surgeons should thus ensure that their patients are adequately dosed with vancomycin using the recommendation of 15mg/kg and that the dose of vancomycin is administered in a timely fashion. Furthermore, and based on the findings of this study, we have moved toward limiting the utilization of vancomycin prophylaxis for patients undergoing elective arthroplasty at our institution. Level III, therapeutic study.

Reducing Iodine Contrast Volume in CT Angiography of the Abdominal Aorta Using Integrated Tube Potential Selection and Weight-Based Method Without Compromising Image Quality.

The purpose of this study is to determine whether image quality was maintained when a weight-based protocol incorporating tube potential selection was used to select lower iodine contrast volumes for aortic CT angiography (CTA). Patients with potentially decreased renal function underwent CTA performed with the iodinated contrast volume determined using a table incorporating different tube potentials and patient weights. The image quality of CTA examinations performed with a reduced iodine volume (hereafter known as "low-iodine CTA examinations"), internal control CTA examinations (i.e., prior examinations), and size-matched control CTA examinations was evaluated in separate reading sessions conducted by three vascular radiologists who were blinded as to the contrast volume and tube potential used. Side-by-side unblinded comparison of the examinations was also performed. Aortic attenuation and the contrast-to-noise ratio were measured. Comparisons were performed using the Wilcoxon signed rank test. Fifty low-iodine CTA examinations, 36 internal control CTA examinations, and 50 size-matched control CTA examinations were performed. Contrast volumes were 63% lower when the protocol based on tube potential and patient weight was used (mean contrast volume, 49 mL for low-iodine CTA vs 133 mL for internal control CTA and 138 mL for size-matched control CTA). The mean volume CT dose index was 15.1 mGy for low-iodine CTA versus 18.8 mGy for internal control CTA (p < 0.001), and 15.3 mGy for low-iodine CTA versus 17.1 mGy for size-matched control CTA (p = 0.11). Of the image quality and diagnostic confidence evaluations for low-iodine CTA examinations, over 97% had acceptable image quality and diagnostic confidence for blinded (50/50) and unblinded (35/36) comparisons. Aortic attenuation was similar between groups (p = 0.13-0.71). A weight-based protocol that incorporates tube potential selection allows the use of substantially lower volumes of iodinated contrast material in aortic CTA while maintaining acceptable image quality.

A Comparison of an Individualized and Weight-Based Opioid Protocols for the Treatment of Vaso-Occlusive Episodes in the Emergency Department

▪Introduction: Vaso-occlusive episodes are the most common complication experienced by individuals with sickle cell disease (SCD). Treatment in an emergency department (ED) is often required and significant variability in care exists. In 2014, NHLBI published evidence based recommendations suggesting treatment with either an individualized opioid dosing or standard weight-based protocol; however the supporting evidence grade was Consensus - Panel Expertise. As outlined in the results section, the aim of this project was to compare change in pain scores, patient safety and system utilization variables between patients randomized to an individualized or weight based (standard) dosing protocol for treatment of VOC from arrival to discharge in an ED setting.Methods: A randomized controlled trial was conducted in two EDs (OH and NY). Adults with SCD were eligible for inclusion and recruited during a hospitalization, clinic visit or at the end of an ED visit. Patients were randomized to treatment with an individualized opioid dosing protocol (developed by the SCD physician based on patients' prior opioid use) or standard weight based protocol. Both protocols were supported by the NHLBI recommendations for treatment of VOE (2014) to include repeat dosing. Protocols were made available on the electronic medical record for future ED visits (up to five visits/patient), should they occur. ED physicians were informed of the protocol and ordered analgesics. Research staff was notified when ED visits occurred for enrolled patients and obtained assessments of pain (0-100 cm VAS) every 30 minutes from placement in the ED to one of 3 study endpoints: 1) 6 hours; 2) decision to admit to the hospital; 3) discharge home. The unit of analysis was the ED visit rather than patient. The primary outcome was change in pain score from arrival to study endpoint. Research staff reviewed the medical record 30 days after the ED visit to determine secondary outcomes of hospital admission, re-admission and new ED visits within 72 hours, 7 and 30 days post the index ED visit. The medical record was reviewed for administration of narcan, intubation, or assisted ventilation. A hierarchical linear mixed effects model adjusting for nested patient and site effects were used to test for a difference in the mean pain change scores in the treatment arms. Generalized Linear Models adjusting for nested patient and site effects were performed to evaluate differences in the dichotomized secondary outcomes.Results: 106 patients enrolled in the study with 52 patients (sites: 25 OH, 27 NY) contributing a total of 126 ED visits over 12 months. Among the 52 patients with visits, the median number of ED visits/patient was 2.0, 58% were male, and the median age was 27 years (range: 21 to 60). No patients in either treatment arm required narcan, intubation, or assisted ventilation.Pain change: Mixed effect model adjusted mean ± standard deviation, higher positive score = greater pain reduction; *Fisher’s Exact Test result due to low cell frequency.Conclusions: An individualized opioid dosing protocol resulted in a larger reduction in pain scores and lower hospital admission rate among patients with SCD treated for VOE in two EDs when compared to treatment with a weight-based opioid protocol. However, there was a tendency for more frequent ED re-visits within 72 hours, 7 and 30 days among patients in the individualized opioid dosing protocol. A pragmatic RCT with a larger and more heterogeneous sample of patients and ED settings is required to provide definitive evidence to guide treatment of VOE. [Display omitted] DisclosuresTanabe:NHLBI: Research Funding. Bosworth:WestMeadVaco: Research Funding; CVS carematix: Consultancy; Improved Patient Outcomes: Research Funding; Johnson & Johnson: Consultancy, Research Funding; Genentech: Consultancy; sanofi: Honoraria, Research Funding; Pharma Foundation: Research Funding.

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.

Rituximab Desensitization in Pediatric Patients: Results of a Case Series.

Rituximab is a monoclonal antibody (mAb) primarily used to treat oncologic and autoinflammatory conditions. Although hypersensitivity reactions (HSRs) and desensitization protocols to mAbs have been well described in adults, the experience in the pediatric population is very limited. We sought to determine the safety and efficacy of desensitization to rituximab in the pediatric population at our institution. We retrospectively reviewed the experience with HSRs and desensitization to rituximab during a 5-year period in our tertiary care pediatric center, including reaction evaluation, premedication regimens, and desensitization procedures and protocols. A total of 17 desensitizations to rituximab were performed in three patients. A 14-year-old patient underwent successful desensitization to rituximab using a published adult protocol without incident. Two younger patients (ages 7 years and 23 months) experienced significant reactions during initial desensitization attempts. Therefore, we designed a modified desensitization protocol to rituximab, with particular attention to the rate of infusion as mg/kg/h. This new patient weight-based protocol was successfully used in a total of 13 desensitizations in these two patients. Desensitization to rituximab was a safe and effective procedure in our pediatric population. We present a new patient weight-based desensitization protocol for pediatric patients who develop HSRs to rituximab, with particular usefulness for younger pediatric patients and potential utility in pediatric patients with HSRs to other mAbs.

A Comparison of Morphine Delivery in Neonatal Opioid Withdrawal.

Current estimates of the prevalence of opioid withdrawal in newborns from the 2012 Better Outcomes Registry and Network Ontario reveal that more than 4 births per 1000 display recognizable symptoms of neonatal abstinence syndrome (NAS). With a growing consensus surrounding aspects of newborn opioid withdrawal care, clinicians might agree that all infants exposed to maternal opioids require supportive observation and care to ensure appropriate adaptation and growth in the newborn period and, likewise, that there exists a smaller percentage of newborns who require additional pharmacotherapy. However, due to the dearth of comparative studies of NAS tools, there remains a lack of evidence to support the use of a specific NAS method of scoring or treatment. Two types of NAS treatment protocols currently in use include a symptom-only versus weight-based protocols. Our Neonatal Intensive Care Unit (NICU) has used both models. A formal structured NAS tool and weight-based morphine delivery system began in our NICU in 1999. We audited all newborns with known exposure to maternal opioids in our NICU from the years 2000 to 2014. The Finnegan scoring tool was used throughout all years of the chart audit. Modifications made to the Finnegan scoring tool from the MOTHER study were adapted for use in our NICU at the same time as adopting the Johns Hopkins model of symptom-only based morphine delivery in 2006. The objective of this comparative study using a retrospective chart audit is to compare length of stay (LOS) and total accumulative morphine dose across these two morphine delivery protocols. Our audit revealed that there were a significantly higher proportion of newborns in the symptom-only model that received morphine and, perhaps accordingly, also had a significantly higher LOS compared to those in the weight-based model. Comparing only those infants who did receive morphine, the comparative total accumulative dose of morphine and LOS were not significantly different between the weight-based and symptom-only morphine delivery models.

Ultrasound-Guided Botulinum Toxin Type A Salivary Gland Injection in Children for Refractory Sialorrhea: 10-Year Experience at a Large Tertiary Children's Hospital

BackgroundSialorrhea is problematic for neurologically impaired children, and botulinum toxin A salivary gland injection has been reported as effective in reducing sialorrhea. This article assesses the success and safety of ultrasound-guided weight-based botulinum toxin A injection for the management of sialorrhea in children. MethodsA total of 111 patients (63 males; 48 females; average age 7 years) with refractory sialorrhea were treated with ultrasound-guided botulinum toxin type A salivary gland injections (144 procedures) from July 1, 2004, to July 1, 2014, using a single weight-based protocol. Patient history, procedural records, and clinical follow-up documents were retrospectively reviewed. Clinical data were compared with reported effectiveness and complications using odds ratios. ResultsA total of 144 procedures were performed in 111 patients with refractory sialorrhea. Cerebral palsy was the most common underlying etiology for sialorrhea (29%), whereas others included encephalopathy (5%), anoxic brain injury (4%), and a variety of chromosomal anomalies (5%). There was a 100% technical success rate. Overall treatment effectiveness was 68%. Repeat injections were not associated with increased clinical success. No procedure-related deaths or major complications were identified; the minor complication rate was less than 2%. ConclusionsThe protocol used for ultrasound-guided injection of botulinum toxin A proved to be safe and effective in children suffering from sialorrhea. Image guidance technique may lead to a reduction in rates of adverse events reported in other series. Subsequent procedures do not improve upon initial efficacy.

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.

Optimal Manual Exchange Transfusion Protocol for Sickle Cell Disease: A Retrospective Comparison of Two Comprehensive Care Centers in the United Kingdom and Canada

Chronic red blood cell (RBC) transfusion is employed for a wide range of sickle cell disease complications, ranging from primary and secondary stroke prophylaxis to prevention of painful vaso-occlusive episodes. Currently different methods are employed by centers for chronic transfusion that include simple, automated and partial manual RBC exchange transfusion. A retrospective cohort study of two different manual RBC exchange transfusion methods was conducted between two comprehensive care centers in Toronto, ON, Canada and London, United Kingdom in 19 and 21 sickle cell disease adults, respectively. London used a weight-based protocol, while Toronto used a unit-based method. Our results indicated that sickle cell disease patients utilizing a weight-based method are more often unable to achieve the prescribed Hb S (HBB: c.20A > T) target compared to the unit-based method (90.0 vs. 53.0% in the weight-based and unit-based methods, respectively, p = 0.0123). On multivariable logistic regression, none of the covariates examined was found to influence the ability to achieve the prescribed Hb S target after accounting for the exchange transfusion method. Mean interval of exchange sessions, session duration, total units of packed RBC, volume of blood used by body weight each year, the mean post exchange hematocrit [or packed cell volume (PCV)] and ferritin change were similar in both cohorts. In conclusion, the unit-based method was more effective at maintaining the prescribed Hb S target.

Weight-based hypoglycaemia treatment protocol for adults with Type 1 diabetes: a randomized crossover clinical trial.

To determine whether a weight-based hypoglycaemia treatment using 0.3g/kg (or 0.2g/kg) glucose effectively treats adults with Type 1 diabetes mellitus compared with an internationally recommended 15-g treatment. Patients with frequent hypoglycaemia were recruited from hospital-based diabetes clinics. The treatment for each hypoglycaemic episode, defined as capillary glucose <4.0mmol/l, was randomly assigned to one of three protocols: 0.2g/kg, 0.3g/kg, or 15g, using Dextro(TM) glucose tablets (Dextro Energy, Krefeld, Germany). Each participant received each treatment in random order for up to 15 hypoglycaemic episodes. Capillary glucose was re-tested 10min after treatment, with a repeat dose if still < 4mmol/l. The study recruited 34 participants aged 22-71years, whose mean (sd) BMI was 25.2 (3.1) kg/m(2) and HbA1c 63 (10.4) mmol/mol [7.9 (0.9)%]. Two people withdrew because they did not like the taste of the Dextro tablets and one was excluded because they used their own glucose preparation. Unadjusted for clustering within participants, the mean (sd) capillary glucose after 10min was 4.67 (1.25) mmol/l for 0.3g/kg (141 episodes), 4.29 (0.94) mmol/l for 0.2g/kg (132 episodes), and 4.37(0.99) mmol/l for 15g (136 episodes). Capillary glucose, adjusted for clusters and baseline, was higher after 10min for 0.3g/kg glucose compared with 15g glucose; a difference of 0.26 (95% CI 0.04-0.48) mmol/l (P=0.02), but not for 0.2g/kg; -0.07 (95% CI -0.29-0.16) mmol/l (P=0.56). Capillary glucose for only three hypoglycaemic episodes rose above 8mmol/l. A weight-based protocol of 0.3g/kg glucose appears more effective for treating symptomatic hypoglycaemia in adults with Type 1 diabetes than either the most common current recommendation of 15g glucose or a 0.2g/kg glucose dose.

Obesity increases risk of anticoagulation reversal failure with prothrombin complex concentrate in those with intracranial hemorrhage

Background: Not all patients with warfarin-related acute intracranial hemorrhage (ICH) achieve full reversal of international normalized ratio (INR) after the first dose of weight-based prothrombin complex concentrate (PCC). We sought to identify factors associated with anticoagulation reversal failure after the first dose of PCC. Methods: Consecutive patients who were hospitalized with warfarin-related acute ICH at a tertiary center between 1 January 2010 and 31 December 2012 were studied. Anticoagulation reversal failure was defined as INR ≥ 1.5 after the first dose of PCC. Logistic regression was performed to determine the predictors of anticoagulation reversal failure. Results: Fifty-one patients with acute ICH received PCC for warfarin reversal using a weight-based protocol. Overall, 23 (45%) patients did not achieve full reversal of INR after the first dose. Those with anticoagulation reversal failure were obese (body mass index > 30 kg/m2) (41% vs. 14%, p = 0.03), had a higher initial INR (3.0 ± 1.4 vs. 2.0 ± 0.7, p = 0.001), and had a higher prevalence of initial INR >2.0 (22% vs. 67%, p = 0.001), compared with those who were successfully reversed. Multivariable logistic regression identified obesity (odds ratio 7.88, 95% CI 1.12 to 55.68) and initial INR >2.0 (odds ratio 12.49, 95% CI 2.27 to 68.87) as independent predictors of anticoagulation reversal failure. Conclusions: Obesity and elevated initial INR are independently associated with anticoagulation reversal failure using the weight-based PCC protocol in patients with warfarin-related acute ICH. Further studies are needed to determine more effective dosing protocols and individualized strategies for anticoagulation reversal after acute ICH, especially among obese patients.

Case Report: Efficacy and Tolerability of Ketamine in Opioid-Refractory Cancer Pain

ABSTRACTA 36-year-old female with metastatic breast cancer involving bones, liver, lung, and pleura/chest wall with worsening back pain received weight-based intravenous (IV) ketamine and was transitioned to oral ketamine for cancer-related neuropathic pain. She had responded poorly to outpatient pain regimen of oxycodone sustained and immediate release, hydromorphone, gabapentin, and duloxetine (approximate 480 mg total oral morphine equivalents [OME]), reporting an initial pain score of 10/10. She was started on hydromorphone parenteral patient-controlled analgesia (PCA) bolus dose in addition to her outpatient regimen. Despite escalating doses of opioids and the addition of a lidocaine 5% patch, the patient's pain remained uncontrolled 6 days after admission. On hospital day 7, utilizing a hospital weight-based ketamine protocol, the patient was started on subanesthetic doses of ketamine at 0.2 mg/kg/h (288 mg/24 h) and titrated over 2 days to 0.4 mg/kg/h (576 mg/24 h). Then, a 3-day rotation from intravenous to oral ketamine was initiated, and the patient was discharged on ketamine oral solution, 75 mg every 8 hours. When the patient's dose was increased to 0.4 mg/kg/h, adequate pain relief was charted by the nurse within 120 minutes, “patient pain free and resting comfortably.” Her pain continued to be well managed, with an average pain score of 5/10 with the ketamine continuous infusion and sustained with conversion to oral ketamine without any report of side effects. This was a 37% reduction in pain scores. With the patient's stabilized dose of ketamine, opioid requirements decreased by 61.4% (1017.5 mg reduction in total OME). The use of weight-based dosing of IV continuous infusion and transition to oral ketamine was effective and tolerable in the management of opioid-refractory, neuropathic cancer pain. It is hoped that this case report promotes a discussion regarding ketamine dosing in refractory neuropathic cancer pain.