Abstract
Introduction
Pain management is a critical aspect of burn patient care, yet the optimal dosing strategy for narcotics is unclear. Cytochrome P450 enzymes (CYP), responsible for metabolism of ...many opioids used in burns, have multiple polymorphisms. Mutant CYPs exhibit fast, intermediate, or slow/null characteristics altering drug pharmacokinetics (PK) and pharmacodynamics(PD), resulting in therapeutic failure or life-threatening toxicity. Unfortunately, CYP genotyping has not been applied to opioid dosing. Fentanyl and other opioids, drugs used ubiquitously in critically ill patients, are metabolized by CYP, particularly the CYP3A4 and 2D6 subtypes. Many co-administered drugs also compete for the same CYP2D6/3A4 pathways or act as CYP inducers or inhibitors to further alter enzyme activity, affecting PK/PD and treatment outcomes. The objectives of the current study were to determine the effects of CYP2D6 and 3A4 polymorphisms on fentanyl PK in adult burn patients.
Methods
Blood samples from 13 adult burn patients with 22–74% total body surface area burns where used for this study. Each patient was administered a 70 µg continuous rate infusion of fentanyl and blood samples were collected at 0, 15, 30 and 60 minutes following initial start of infusion. Blood samples where used for CYP genotyping by PCR and fentanyl blood concentrations where determined using high performance liquid chromatography - tandem mass spectrometry. A two-compartment population PK model was developed using Monolix software.
Results
Three polymorphisms resulting in decreased fentanyl metabolism where identified which included CYP2D6*9, 2D6*29 and 3A4*1B. All three patients had increased serum fentanyl concentrations compared to wildtype. Fentanyl blood clearance was significantly reduced in 2D6*9, 2D6*29 and 3A4*1B patients compared to wildtype, 9.13, 4.13, 5.7 and 1142.2 mL/min respectively.
Conclusions
The CYP2D6*9, 2D6*29 and 3A4*1B polymorphisms do significantly alter the clearance and volume of distribution in adult burn patients, thus resulting in increased circulating fentanyl blood concentrations.
Applicability of Research to Practice
This study supports CYP genotyping of individual patients prior to opioid administration to inform precision-guided decisions, improve therapeutic efficacy, and, most importantly, increase patient well-being and safety. Therefore, combining CYP screening with identifying CYP inducing/inhibiting drugs may improve precision of opioid therapy.
Abstract
Introduction
Dermal substitutes can be an essential treatment option for patients with very large burn injuries. We reviewed and compared our experience with a fetal bovine dermis dermal ...substitute versus allograft for adult burn patients with large burn injuries.
Methods
After obtaining regulatory approval from our local institutional review board, we performed a 1 year retrospective review of adult burn patients with a TBSA of 50% or greater who underwent grafting with either fetal bovine dermis or allograft. We collected data that included age, TBSA, length of stay, number of operations, % area grafted with either allograft or fetal bovine dermis, and time between allograft or fetal bovine dermis grafting to autografting. All mean values are mean ± standard deviation, and all median values are median (interquartile range)
Results
Overall for this review 15 patients met entry criteria. The mean age was 36 ± 9 years and mean TBSA was 71 ± 15%. Mean area grafted with either allograft (A) or fetal bovine dermis (FB) was 20 ± 8%. Mean time from grafting with A or FB was 30 ± 12 days. There was no difference in median age between the A group (30 (26–31)) and FB group (35 (32–46) and there was no difference in median TBSA between the A group (68(60–75)%) and FB group (69(59–88)%). The median area grafted with allograft was 20(20–30)% which was not significantly different than the median area grafted with FB (16.5(11–26)%). Additionally, there was no difference between the time from grafting with A to autografting (26(22–36) days) and the time from grafting with FG to autografting (25.5(21–32) days).
Conclusions
Fetal bovine dermis may be an acceptable alternative to allograft in patients with a large TBSA burn-injury. In areas of the world without a tissue bank, fetal bovine dermis may provide a durable option for treating large burn injuries. Further studies are needed to determine if infectious and functional outcomes are improved with fetal bovine dermis.
Applicability of Research to Practice
Use of dermal substitute for large burn injuries.
Abstract
Introduction
Children with major burn injury frequently require prolonged central venous access to assure appropriate fluid management and pain control. Central venous catheters in children ...frequently develop clots that prevent drug administration. Tissue plasminogen activator (TPA) is one of the methods employed to relieve the catheter obstruction, yet the frequency and efficacy of TPA use in central line infections in burned children is not well defined. The purpose of this study was to identify the frequency and efficacy of TPA use in burned children with central lines.
Methods
This retrospective chart review evaluated all children admitted to our tertiary pediatric burn center in 2016 who required central venous catheters. Data collected included patient factors (age, burn size, hospital length of stay), catheter-related data (number of central lines, lines replaced due to clotting prior to scheduled changes), TPA administration (number of times administered, how many administrations successful, how many times repeated), and line clotting data (time from insertion to clot, interval between TPA order and administration).
Results
A total of 156 lines were place in 48 children with mean age of 7 years and mean burn size of 33% TBSA, LOS was 31 days in the PICU. TPA was used in 12.8% of lines to relieve obstruction. TPA use was successful in relieving the clot 20% of the time (4/20). The interval between identification of the obstructed line to TPA order was 96 minutes, with the administration of TPA 181 minutes after the order was placed. The average time from identification of obstruction to TPA administration was 227 minutes.
Conclusions
The incidence of obstruction in pediatric central venous catheters in our unit was approximately 12%, and 20% of those obstructions were cleared with TPA. Based on our results we have targeted areas for improvement including: charting documentation, frequency of flushing unused central venous catheter lumens, reeducating the staff on TPA usage and decreasing our average times to identify, order, and administer TPA.
Applicability of Research to Practice
Optimizing and maintaining central line patency.
Abstract
Introduction
In children with burn injuries, nutritional needs are significantly increased to promote healing and help keep them on their predicted growth curve. This is especially apparent ...in the 0–5 year pediatric population, as this is period of rapid growth. To help our patients meet the increased nutrient needs, we insert post-pyloric feeding tubes in our patients with >20% TBSA and begin enteral feedings on admission. Most patients with <20% TBSA will consume a regular oral diet. The goal of this study is to determine if our 0–5 year pediatric patients with >10% TBSA stay on their projected growth curve upon discharge.
Methods
After obtaining regulatory approval from our local institutional review board, we performed a retrospective review of pediatric burn injured patients admitted to our center from January of 2010 to August of 2017. The inclusion criteria for the study included the following: 0–5 year old with greater than 10% TBSA burns who were hospitalized for more than 10 days. The following data was collected and analyzed: demographics, nature and extent of burn injury, length of hospital stay, admission weight with growth scale percentile and discharge weight with growth scale percentile.
Results
A total of 170 pediatric patients met the criteria for our study. Of these patients the median age was 2.6(sd=1.6) years, 99 patients were male and 71 were female. The average TBSA percentage was 25% (sd=13.5%), median length of stay 27 days (range of 17–42). Of the 170 patients 90 received tube feedings. The average admission weight was 14.5kg (sd=4.8), average discharge weight 13.9 (sd=4.4) there was a median weight loss of only 0.5kg. Using the World Health Organization’s pediatric growth scale our patients averaged on the 70th percentile on admission with a median decrease of 8.15 percentiles upon discharge. All patients with 40% TBSA or greater received tube feeds. Tube fed patients overall gained more weight, however they did not have a significantly different change in growth scale percentile. There was no difference in weight gain or growth scale change in patients with a TBSA of 10–19% between tube fed and non-tube fed patients. There was a significant increase in both weight and growth scale in patients who were tube fed with a TBSA of 20–39% compared to non-tube fed patients.
Conclusions
In patients with moderate to severe burn wounds, tube feedings may improve or maintain both weight and growth velocities. Further study is needed on the long term effects of moderate to severe burns on growth velocity.
Applicability of Research to Practice
Pediatric burn patients have increased nutritional needs to promote healing and to maintain their natural growth velocity. This study further indicates the need to provide optimal nutrition via enteral nutrition for large burns in order to promote healing and maintain a normal growth curve.
Inflammation is postulated to play an important role in ovarian carcinogenesis. Prostaglandin endoperoxide synthase 2 (PTGS2) is responsible for the conversion of arachidonic acid to prostaglandins ...in response to inflammation. In a pooled analysis of two population-based studies, the Hawaii Ovarian Cancer Case-Control Study and the New England Case-Control Study, including 1,025 women with invasive ovarian carcinoma and 1,687 cancer-free controls, the association of ovarian cancer risk with the PTGS2 rs5275 polymorphism and the use of nonsteroidal antiinflammatory drugs (NSAIDs) were examined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. In the pooled analysis, the CC genotype was associated with a reduced risk of nonserous ovarian carcinoma (OR = 0.66; CI: 0.44-0.98). In addition, the lowest risk was observed among carriers of the CC genotype who were users of only nonaspirin NSAIDs (OR = 0.43; CI:0.20-0.93) in all women combined. The association of PTGS2 rs5275 with nonserous ovarian carcinoma and possible effect modification by NSAID use needs further validation, preferably in prospective studies.
Over 22,000 cases of ovarian cancer were diagnosed in 2007 in the United States, but only a fraction of them can be attributed to mutations in highly penetrant genes such as BRCA1. To determine ...whether low-penetrance genetic variants contribute to ovarian cancer risk, we genotyped 1,536 single nucleotide polymorphisms (SNP) in several candidate gene pathways in 848 epithelial ovarian cancer cases and 798 controls in the North Carolina Ovarian Cancer Study (NCO) using a customized Illumina array. The inflammation gene interleukin-18 (IL18) showed the strongest evidence for association with epithelial ovarian cancer in a gene-by-gene analysis (P = 0.002) with a <25% chance of being a false-positive finding (q value = 0.240). Using a multivariate model search algorithm over 11 IL18 tagging SNPs, we found that the association was best modeled by rs1834481. Further, this SNP uniquely tagged a significantly associated IL18 haplotype and there was an increased risk of epithelial ovarian cancer per rs1834481 allele (odds ratio, 1.24; 95% confidence interval, 1.06-1.45). In a replication stage, 12 independent studies from the Ovarian Cancer Association Consortium (OCAC) genotyped rs1834481 in an additional 5,877 cases and 7,791 controls. The fixed effects estimate per rs1834481 allele was null (odds ratio, 0.99; 95% confidence interval, 0.94-1.05) when data from the 12 OCAC studies were combined. The effect estimate remained unchanged with the addition of the initial North Carolina Ovarian Cancer Study data. This analysis shows the importance of consortia, like the OCAC, in either confirming or refuting the validity of putative findings in studies with smaller sample sizes. (Cancer Epidemiol Biomarkers Prev 2008;17(12):3567-72).
•From 560 screened references, we included 4 studies. Out of 5978 patients, 2893 (48%) reported a cooling duration of ≥20 min•IWe found no association between duration of cooling and size/depth of ...burn, days to re-epithelialization or skin grafting.•Confidence in the estimate of effect, for the outcomes evaluated, was very low due to very serious risk of bias
Cooling thermal burns with running water is a recommended first aid intervention. However, guidance on the ideal duration of cooling remains controversial and inconsistent across organisations.
To perform a systematic review of the evidence for the question; Among adults and children with thermal burn, does active cooling using running water as an immediate first aid intervention for 20 min or more, compared with active cooling using running water for any other duration, change the outcomes of burn size, burn depth, pain, adverse outcome (hypothermia) or complications?
We searched Medline, Embase, Cochrane Database of Systematic Reviews and used ROBINS-I to assess for risk of bias. We used Grading of Recommendations, Assessment, Development and Evaluation methodology for determining the certainty of evidence. We included all studies that compared the selected outcomes of the duration of cooling of thermal burns with water in all patient ages. (PROSPERO registration number: CRD42021180665). From 560 screened references, we included four observational studies. In these studies, 48% of burns were cooled for 20 min or more. We found no benefit for a duration of 20 min or more of cooling when compared with less than 20 min of cooling for the outcomes of size and depth of burn, re-epithelialization, or skin grafting. The evidence is of very low certainty owing to limitations in study design, risk of bias and indirectness.
The optimal duration of cooling for thermal burns remains unknown and future prospective research is indicated to better define this treatment recommendation.
We performed case-control analyses using data from the North Carolina Ovarian Cancer Study to determine risk factors that distinguish primary peritoneal cancer (PPC) from epithelial ovarian cancer ...(EOC). Our risk factor analyses were restricted to invasive serous cancers including 495 EOC cases, 62 PPC cases and 1,086 control women. Logistic regression analyses were used to calculate adjusted odds ratios and 95% confidence intervals for risk factor associations. Although many case-control associations for the invasive serous PPC cases were similar to those of the invasive serous EOC cases, some differences were observed including a twofold increase in risk of invasive serous PPC in women who were ≥35 years at last pregnancy, whereas a decreased risk was observed for invasive serous EOC risk. We could not confirm a previous report of an association between tubal ligation and PPC, a factor consistently associated with a decreased risk of EOC. The difference in the risk factor associations between invasive serous PPC and EOC cancers suggests divergent molecular development of peritoneal and ovarian cancers. A larger study to determine risk factors for invasive serous PPC is warranted.
Abstract
Introduction
Methamphetamine (MA) is one of the most abused stimulants in the United States. In the burn injured population, it has been linked to more frequent inhalation injuries, larger ...resuscitation volumes, and higher complication rates. MA use is also associated with anxiety and pain experienced during treatment and recovery. There is a paucity of literature examining the impact of MA abuse on pain control and opioid requirements in the burn injured population. The aim of this work was to examine the impact of MA abuse on discharge pain scores and opioid requirements.
Methods
A retrospective review was performed on burn injured patients admitted to a burn center from 2016 to 2017. Patients whose injury were non-acute burn related, had a hospital stay <24 hours, or died were excluded. Data on demographics, burn size (TBSA), social history (SH), admission toxicity screening, discharge pain scores, length of stay (LOS), and opioid equivalents (OE) in their last 24 hours of admission were collected. OEs were determined by converting all narcotics to oral morphine equivalents.
Results
During the study period, 285 patients met inclusion criteria. Only 199 (69.8%) patients received a toxicity screen on admission. Among those screened, 81 (40.7%) patients were positive for MA use. In patients who received a toxicity screen, there were no differences in LOS (11.9 v 16.5 days, p=0.059), OEs (77.8 vs. 90.5, p=0.22), or OE/TBSA (16.6 vs. 18.2, p=0.65) in patients who screened positive for MA vs those screened negative. MA positive patients had higher discharge pain scores (4.37 v 3.48, p=0.03) than patients who screened negative. Given that over 30% of patients did not have a toxicity screen, we examined patients with a SH of illicit drug use. SH data was available for 275 patients (96.8%) with 150 negative SH (54.5%), and 121 positive SH (44%). There was no difference between those who had negative SHs and those with positive SHs with regards to LOS (16.1 vs. 15.8, p=0.98), or OE/TBSA (18.5 vs. 19.6, p=0.79). Patients with a positive SH used more OEs in the last 24 hours of hospitalization (92.2 vs. 72.9) but this did not reach significance (p=0.057). Patients with a positive SH of illicit drug use had higher pain scores at discharge (4.10 vs. 3.21, p=0.01).
Conclusions
We strive to obtain drug screens on all patients admitted with a burn injury, but fall short of this goal in practice. Patients who screened positive for MA use and those with a social history of illicit drug use had higher pain scores at discharge. Additional work will be necessary to fully elucidate these results and determine techniques to improve pain control.
Applicability of Research to Practice
We need to make improvements in our screening of patients for illicit substances and in controlling the pain at discharge in patients with a history of illicit drug use.
Abstract
Introduction
Hip extension limitations are a common issue in our pediatric burn unit although their occurrence is not well documented in the literature. If untreated, these limitations can ...lead to chronic hip flexion contractures that result in abnormal gait patterns and inability to stand with erect posture. In children, these contractures could also lead to alteration of bony development. A review of published hip splinting techniques includes the thermoplastic anterior hip splint and the bivalve thermoplastic trunk/hip splint. Bivalve spica casts for post-op and nighttime splinting represent a cost-effective and valuable tool to provide a sustained stretch to the anterior hips. This report aims to share preliminary results from a quality assurance project looking at a series of patients who utilized this cast and to explain how the bivalve spica cast is made.
Methods
The bivalved spica cast was used on 10 patients. The average patient age was 6y4m (range 1y11m to 11y). Patients were primarily selected for casting if they had not responded to less restrictive splinting (thermoplastic anterior hip splint, abduction wedge) or positioning. Nine of these patients were inpatient at the time of casting. Six patients were casted in the OR under sedation and 4 patients were casted while awake. Fiberglass casting was performed by a orthopedic technician with a physical therapist assisting with positioning. A child life specialist was present when the patients were awake to provide comfort and distraction. All casts were bivalved, lined with waterproof tape along the edges, and had straps and buckles attached. All patients were discharged home with the cast to be used while sleeping at night in prone or supine.
Results
Patients who used the bivalve spica casts showed improvement in hip range of motion as measured either goniometrically (average increase in hip extension was 10° with a range of 0°to 25°) or functionally (i.e. improved gait mechanics, ability to lie prone). One cast was broken (due to moisture) and had to be remade. There were no complications reported.
Conclusions
The bivalve spica cast is a valuable splinting tool for the management of post-burn pediatric hip flexion contractures. The cast is easily fabricated and does not require expensive materials. Casting is most successful with a team approach. Drawbacks include the time involved to coordinate team members as well as the cast not being waterproof.
Applicability of Research to Practice
A cost-effective means of managing hip flexion contractures in pediatric patients.
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