An Appraisal of Pharmacotherapy-Pertinent Literature Published in 2021 and 2022 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Studies focusing on pharmacotherapy interventions to aid patients after thermal injury are a minor focus in burn injury-centered studies and published across a wide array of journals, which challenges those with limited resources to keep their knowledge current. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Twenty-three geographically dispersed, board-certified pharmacists participated in the review. A Medical Subject Heading-based, filtered search returned 2336 manuscripts over the previous 2-year period. After manual review, 98 (4%) manuscripts were determined to have a potential impact on current pharmacotherapy practice. The top 10 scored manuscripts are discussed. Only 17% of those reviewed were assessed to likely have little effect on current practice. The overall impact of the current cohort was higher than previous editions of this review, which is encouraging. There remains a need for investment in well-designed, high-impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.

Precipitation of hyponatremia and seizures by esmolol in sterile water formulation.

PURPOSE: Acute hyponatremia can lead to severe neurological symptoms such as confusion, obtundation, seizures, coma, and respiratory depression, contributing to increased morbidity and mortality. Patients with acute hyponatremia should be evaluated based on volume status and serum osmolality to determine potential causes and appropriate treatment. The aim of this case report is to illustrate the importance of using a multidisciplinary approach to evaluate medication formulation and the potential impact on a patient's clinical course. SUMMARY: A 34-year-old male was admitted for type A aortic dissection and was treated with an esmolol infusion and underwent operative repair. Two days after initiation of esmolol, the patient developed seizures and antiepileptics were initiated. The patient's serum sodium concentration was found to have decreased by a total of 14 mEq/L since admission. The patient had received more than 6 L of esmolol formulated in sterile water over the course of 2 days. The esmolol infusion was converted to another antihypertensive agent, and 0.9% sodium chloride injection was initiated, after which the serum sodium concentration began to recover. No further seizures were observed on continuous electroencephalography, and all antiepileptic drugs were discontinued with no seizure activity. CONCLUSION: The esmolol product utilized in this case was formulated in 250 mL of sterile water, which is suspected to have contributed to the patient's hyponatremia. It is important to be aware of the formulation and excipients of medications and their potential for adverse effects.

Vitamin D Deficiency Is Associated With Increased Length of Stay After Acute Burn Injury: A Multicenter Analysis.

In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis and infectious complications. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). This was a multicenter retrospective study of adult patients at 7 burn centers admitted over a 3.5-year period, who had a 25-hydroxyvitamin D concentration drawn within the first 7 days of injury. Of 1147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, P < .001), acute kidney injury (AKI) requiring renal replacement therapy (7.3 vs 1.7%, P = .009), more days requiring vasopressors (mean 1.24 vs 0.58 days, P = .008), and fewer ventilator-free days of the first 28 days (mean 22.9 vs 25.1, P < .001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, vitamin D deficiency was associated with longer LOS. In conclusion, patients with thermal injuries and vitamin D deficiency on admission have increased LOS and worsened clinical outcomes when compared with patients with nondeficient vitamin D concentrations.

Presence of variable extrathoracic airflow limitation in patients with a negative methacholine challenge test.

PURPOSE: Determine whether variable extrathoracic airflow limitation (VEAL) is observed in patients with negative methacholine challenge tests (MCT). METHODS: Electronic medical records of patients undergoing MCT at Jesse Brown VA Medical Center between January 2017 and December 2019 were reviewed. Only patients with negative MCT were selected. Pertinent demographic, clinical, and pulmonary function tests (PFT) and MCT data were abstracted from each record. Spirometric flow-volume loops recorded during each test were inspected by one co-author to determine the first inhaled methacholine concentration at which FEF50/FIF50 was either > 1 or further increased if baseline FEF50/FIF50 after nebulized saline (vehicle) already exceeded 1. Student's t-test was used for statistical analysis. P < 0.05 was considered statistically significant. RESULTS: One hundred and twenty-seven consecutive patients with normal baseline PFT and negative MCT were identified. Thirteen patients (10.2%) had negative MCT and FEF50/FIF50 > 1 after testing. They were predominately obese (BMI, 31.3 ± 6.6), non-smoking (10), White (8) males (9) aged 51.3 ± 14.1 years (mean ± SD) referred for symptoms suggestive of asthma (n = 7) or for chronic cough (n = 6). Five had obstructive sleep apnea, three gastroesophageal reflux disease, and two chronic rhinosinusitis. FEF50/FIF50 increased significantly from 0.72 ± 0.21 after nebulized saline (vehicle) to 1.21 ± 0.13 after inhaled methacholine (p < 0.001). Median inhaled methacholine concentration eliciting these responses was 1.0 mg/mL (range, 0.25-16 mg/mL). CONCLUSIONS: VEAL is observed in a subset of patients with a negative MCT. This phenomenon should be recognized and reported to the referring healthcare providers and its clinical significance addressed as indicated.

A Review of the Most Impactful Published Pharmacotherapy-Pertinent Literature of 2019 and 2020 for Clinicians Caring for Patients With Thermal or Inhalation Injury.

Keeping abreast with current literature can be challenging, especially for practitioners caring for patients sustaining thermal or inhalation injury. Practitioners caring for patients with thermal injuries publish in a wide variety of journals, which further increases the complexity for those with resource limitations. Pharmacotherapy research continues to be a minority focus in primary literature. This review is a renewal of previous years' work to facilitate extraction and review of the most recent pharmacotherapy-centric studies in patients with thermal and inhalation injury. Sixteen geographically dispersed, board-certified pharmacists participated in the review. A MeSH-based, filtered search returned 1536 manuscripts over the previous 2-year period. After manual review and exclusions, only 98 (6.4%) manuscripts were determined to have a potential impact on current pharmacotherapy practices and included in the review. A summary of the 10 articles that scored highest are included in the review. Nearly half of the reviewed manuscripts were assessed to lack a significant impact on current practice. Despite an increase in published literature over the previous 2-year review, the focus and quality remain unchanged. There remains a need for investment in well-designed, high impact, pharmacotherapy-pertinent research for patients sustaining thermal or inhalation injuries.

A multicenter study analyzing the association of vitamin D deficiency and replacement with infectious outcomes in patients with burn injuries.

Vitamin D (25OHD) deficiency is associated with poor outcomes in intensive care populations. The primary objective of this 7-center study was to determine if 25OHD deficiency is associated with infectious outcomes in adult burn patients. Generalized linear mixed modeling was used to control for center effect, percent total body surface area burn (% TBSA), age, and presence of inhalation injury. A total of 1147 patients were initially included (admitted January 2016 through August 2019). After exclusions, 234 (56.8%) in the deficient (25OHD<20 ng/mL) and 178 in the non-deficient group (25OHD ≥ 20 ng/mL) remained, surpassing a priori power requirements. The non-deficient group had their concentration drawn earlier (p < 0.001), were more likely to be male (p = 0.006), Caucasian (p < 0.001), have lower body mass index (p = 0.009), lower % TBSA (p = 0.002), and taking a 25OHD supplement prior to admission (p < 0.001). Deficient patients were more likely to have an infectious outcome (52.1% vs 36.0%, p = 0.002), acute kidney injury with renal replacement therapy (p = 0.009), less ventilator free days in the first 28 days (p < 0.001), and vasopressors (p = 0.01). After controlling for center, % TBSA, age, and inhalation injury the best model also included presence of deficiency (OR 2.425 [CI 1.206-4.876]), days until 25OHD supplement initiation (OR 1.139 [CI 1.035-1.252]), and choice of cholecalciferol over ergocalciferol (OR 2.112 [CI 1.151-3.877]). To the authors' knowledge, this is the first multicenter study to evaluate the relationship between 25OHD and infectious complications in burn patients.

Evaluation of a Simplified Risk Stratification Twice-Daily Aspirin Protocol for Venous Thromboembolism Prophylaxis After Total Joint Replacement.

OBJECTIVE: To determine using a simplified risk-stratified protocol to select candidates for aspirin therapy have similar death and postoperative complications as universal warfarin therapy in patients undergoing total joint replacement (TJR). METHODS: Retrospective cohort study comparing 30-day postoperative outcomes 6 months before and after the implementation of the aspirin protocol (January 1, 2015) in patients undergoing TJR. The control group was comprised of patients using warfarin for VTE prophylaxis. The protocol group included patients who used aspirin 325 mg twice-daily or warfarin if deemed high thrombotic risk or aspirin intolerant by the criteria set forth by the aspirin protocol. RESULTS: This study included 449 patients. No difference was found in the rates of 30-day postoperative bleeding, VTE, death, composite end point of VTE and death, and length of stay between the control and the protocol groups (all P > .05). Thirty-day postoperative surgical site infections (SSIs; 5.8% vs 1.2%; P = .02) and return to operative room (OR; 3.9% vs 0.4%; P = .03) were less frequent in the protocol group. CONCLUSION: A simplified risk-stratified protocol used to choose patients for aspirin 325 mg twice-daily therapy is safe and effective in patients undergoing TJR, and SSI and return to OR rates may be lower when compared to universal warfarin therapy.

A Review of the Most Impactful Published Pharmacotherapy-Pertinent Literature of 2017 and 2018 for Clinicians Caring for Patients with Burn or Inhalation Injuries.

Staying current and evaluating literature related to pharmacotherapy in burn or inhalation injury can be difficult as burn care teams are multidisciplinary and pertinent content can be spread across a plethora of journals. The goal of this review is to critically evaluate recently published pharmacotherapy-pertinent literature, assist practitioners staying current, and better identify potential future research targets. Twelve board-certified clinical pharmacists with experience caring for patients with burn and inhalation injuries reviewed and graded scientific literature published in 2017 and 2018. An MeSH-based search revealed 1158 articles related to burns, which were published during the 2-year period. One-hundred fifty one were determined to be potentially related to pharmacotherapy. After exclusions, only 82 (7%) remained for scoring, and the top 10 comprehensively presented. More than half of the reviewed manuscripts were assessed as lacking a significant impact on pharmacotherapy. There is a need for higher impact literature to support pharmacotherapy-pertinent treatment of such complex patients.

Risk Factors Associated with the Development of Transaminitis in Oxandrolone-Treated Adult Burn Patients.

Oxandrolone has proven benefits in thermal burn injury and has become a standard of care. Transaminitis is the most frequent side effect of oxandrolone use, although no risk factors have been identified that increase the risk of transaminitis. The objective was to evaluate the frequency of transaminitis while on oxandrolone and to identify risk factors leading to an increased risk of transaminitis in adult burn patients. This multicenter retrospective risk factor analysis compared two patient groups with and without occurrence of transaminitis, which was detected by an aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >100 mg/dL. Secondary outcomes included percentage increase from baseline for AST/ALT, length of stay, and mortality. After univariable analysis, a multivariable logistic regression analysis was performed to detect possible risk factors leading to transaminitis. A total of 309 patients were included, with transaminitis occurring in 128 patients (41.4%) after 13 (interquartile range [IQR] 8-23) days on oxandrolone. After multivariable analysis, age (odds ratio [OR] 0.91; 95% confidence interval [CI] 0.84-0.99 for a 5-year increase in age), intravenous vasopressor use (OR 1.85; 95% CI 1.05-3.27), and amiodarone use (OR 2.51; 95% CI 1.09-5.77) were independent predictors of transaminitis, controlling for TBSA%. Transaminitis was not significantly associated with length of stay or mortality after adjusting for age and TBSA%. We conclude that patients who are younger and have concurrent amiodarone or vasopressor use have the highest risk of developing oxandrolone induced transaminitis and should be monitored closely.

Vitamin D in burn-injured patients.

Recently, many studies have demonstrated pleotropic effects of vitamin D, including immune modulation and cardiovascular system activity. Sufficient vitamin D concentrations and supplementation of vitamin D may be of benefit in burn-injured patients. Low 25(OH)D has been observed in nearly all pediatric and most adult burn patients. Vitamin D has primarily been studied in pediatric burn patients, focusing on bone marker measurements and the incidence of fractures. The preferred vitamin D dose, formulation, and route of administration remain unknown, and there is limited data on the impact of vitamin D status on clinical outcomes. Further research should focus on determining optimal monitoring strategies, supplementation regimens and clinical outcomes like mortality, length of stay and incidence of sepsis.

How Does SCORTEN Score?

The Toxic Epidermal Necrolysis-specific severity of illness score (SCORTEN) was developed to predict mortality in patients with Stevens Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several studies have attempted to assess the accuracy of SCORTEN with mixed results. The objective of this study is to compare the predicted and actual mortality for patients with SJS/TEN admitted to a single high-volume burn center.This retrospective study included adult and pediatric patients admitted to our burn center with biopsy-confirmed SJS/TEN between February 2008 and February 2016. SCORTEN scores were calculated for each patient on days 1 and 3 of admission. The primary endpoint was predicted vs actual in-hospital mortality. Secondary endpoints included the association of SCORTEN, as well as individual components of SCORTEN, with hospital length of stay, length of stay in the intensive care unit, and in-hospital complications.Of 128 patients included, the mean age was 44.5 years, 40.6% (n = 52) were males, and 50.0% (n = 64) were Caucasians. The median TBSA was 12.25% on day 1 and 25% on day 3. The median SCORTEN at admission was 2 (interquartile range: 1-3.5). There were a total of 20 deaths (17.2%). SCORTEN exhibited good discrimination (c-statistic = 0.83, 95% CI: 0.75-0.91) and performed directionally as expected, but a low but nonsignificant standardized mortality ratio (75.3%, P = .164) and a Hosmer-Lemeshow test of borderline significance (P = .088) make the model's fit unclear.The accuracy of the SCORTEN model in predicting mortality for SJS/TEN patients treated in a burn center remains unclear. This study may encourage future multicenter studies to further clarify its predictive ability and may also enhance future investigation into the use of a reformulated or reweighted SCORTEN.

The Use of Thrombolytic Therapy in the Treatment of Frostbite Injury.

Frostbite can lead to severe consequences including loss of digits and limbs. One of the mechanisms of frostbite includes vascular thrombosis. The use of tissue plasminogen activator (tPA) in frostbite has been shown to be effective in case reports and small prospective studies. A retrospective chart review was performed on all patients admitted for frostbite between January 2008 and April 2015, and six patients were identified as having received treatment with intravenous tPA. Patients received an initial bolus dose followed by a 6-hour infusion of tPA. Five patients (83.3%) were treated with continuous infusion heparin following tPA administration. Three patients (50%) were discharged on aspirin 325 mg daily for 30 days and two patients (33.3%) were discharged on warfarin for 28 days. There were no serious complications noted with tPA. In this case series, there were 65 digits at risk for amputation in six patients. Only 16 digits (24.6%) were partially or completely amputated in three (50%) of the patients. After rapid rewarming, the use of tPA is safe and effective at reducing the number of digits amputated. Patients who had less of a response to tPA were those who had an unknown duration of cold exposure along with drug or alcohol intoxication at presentation. Utilizing a guideline with clear criteria will help facilitate determining appropriate patients to safely treat with tPA for frostbite injury.

Prevalence of Auditory Processing Disorder in School-Aged Children in the Mid-Atlantic Region.

BACKGROUND: Although auditory processing disorder (APD) is a widely recognized impairment, its prevalence and demographic characteristics are not precisely known in the pediatric population. PURPOSE: To examine the demographic characteristics of children diagnosed with APD at a tertiary health-care facility and the prevalence of pediatric APD. RESEARCH DESIGN: A cross-sectional study. STUDY SAMPLE: A total of 243 children (149 boys and 94 girls) who were referred to the Nemours Audiology Clinics in the Delaware Valley for an APD evaluation. The mean ages were 9.8 yr for boys and 9.7 yr for girls. Out of 243 children referred for an APD evaluation, 94 children exhibited one or more auditory processing deficits in the areas of auditory closure, auditory figure ground, binaural integration, binaural separation, and temporal processing. DATA COLLECTION AND ANALYSIS: Demographic and audiological data, clinical history (parental reports on prenatal and postnatal information, birth weight and height, medical and developmental history, otologic/audiological history, education information, behavioral characteristics), and results of the APD test battery were retrospectively obtained from the electronic medical records of each participant. The prevalence of APD was estimated using the total number of students enrolled in the same school attended by each participant in the 2011 academic year as cohort. RESULTS: The prevalence of APD was 1.94 per 1,000 children in this study. We found that prevalence of APD among the children who attended private schools was more than two times higher than the children who attended public schools. The results also revealed that the majority of children referred to the clinics were Caucasian (85.6%), whereas minority groups were underrepresented for this geographical area with only 3.7% of Hispanic or Latino children and 5.8% of Black or African American children. CONCLUSIONS: The estimated prevalence of APD in the current study was lower than the previously published estimates. The difference might be due to the diagnosis criteria of APD among studies as well as the use of school enrollment number as the referenced population to estimate prevalence in our study. We also found a significant difference in APD prevalence depending on the school types. The findings of higher prevalence rates among the children attending private schools and higher proportion of Caucasians children referred for APD evaluation suggest that more children among those in public schools and in the Hispanic and African American groups should have been referred for an APD evaluation. Hence, the current estimate is likely an underestimate of the actual APD prevalence. The low percentage of Hispanic or African American children referred to the clinic for APD evaluations may be related to the socioeconomic status and linguistic differences among the concerned families. The results of this study raise the importance of adapting the APD test battery for children with a different linguistic background as well as increasing awareness of available clinical resources to all families in our area.

Nutrition in Toxic Epidermal Necrolysis: A Multicenter Review.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe exfoliative diseases treated in burn centers due to large skin losses. Literature on SJS/TEN refers to parenteral nutrition (PN) as the preferred route of nutrition support. This study describes nutrition support interventions in SJS/TEN patients admitted to burn centers. MATERIALS AND METHODS: Seven burn centers participated in this Institutional Review Board-exempted retrospective chart review of adults with SJS/TEN admitted from 2000-2012. RESULTS: This analysis included 171 patients with SJS/TEN. Median total body surface area involvement was 35% (n = 145; interquartile range [IQR], 16%-62%). The majority required mechanical ventilation (n = 105). Based on indirect calorimetry, measured energy needs were 24.2 kcal/kg of admit weight (n = 58; IQR, 19.4-29.9). Thirty-one patients did not require enteral nutrition (EN) and started oral intake on hospital day 1 (IQR, 1-2), and 81% required EN support due to inadequate oral intake and remained on EN until day 16 (median hospital day, 16; IQR, 9-25). High-protein enteral formulas predominated. PN was rarely used (n = 12, 7%). Most patients were discharged home (57%), with 14% still requiring EN. CONCLUSIONS: Nutrition support should be considered in patients with SJS/TEN due to increased metabolic needs and an inability to meet these needs orally. Most SJS/TEN patients continued on EN and did not require escalation to PN.