Late hemotoxicity following North American rattlesnake envenomation treated with crotalidae immune F(ab')2 (equine) antivenom and crotalidae immune polyvalent Fab (ovine) antivenom reported to the North American Snakebite Sub-registry.

INTRODUCTION: Late hemotoxicity is common following rattlesnake envenomation treated with crotalidae immune polyvalent Fab (ovine) (FabAV). Initial clinical trials showed crotalidae immune F(ab')2 (equine) (Fab2AV) to be superior to FabAV in preventing late hemotoxicity, but this effect has not been demonstrated in broader populations. This study investigated late hemotoxicity in patients receiving Fab2AV or FabAV after rattlesnake envenomation. METHODS: This is a retrospective analysis of prospectively collected data from patients with snakebite reported to the ToxIC North American Snakebite Registry (NASBR) between January 1, 2019, and December 31, 2020. Inclusion criteria were rattlesnake envenomation and administration of antivenom. Patients were excluded if they received more than one type of antivenom. The primary outcome was occurrence of late hemotoxicity (platelets ≤120 k/mm3 or fibrinogen ≤170 mg/dL) in patients receiving Fab2AV and FabAV. Data collected included demographics, envenomation characteristics, laboratory values, and treatment administered. Statistics including t-test and Fisher's exact test were used. RESULTS: A total of 201 rattlesnake envenomated patients receiving antivenom were reported to the NASBR in the study period; 144 were included. 49 received Fab2AV alone, 45 received FabAV alone and 50 received both antivenoms. Baseline patient and envenomation characteristics were similar between the groups. Late hemotoxicity occurred in 2/49 patients in the Fab2AV group (4% (95% CI 0.7-12.6)) and in 19/45 patients in the FabAV group (42% (95% CI 28.4-59.0); absolute risk reduction 39.1% (95% CI 21.2-46.2) (p = 0.001). On follow up, 0 patients (0%) receiving Fab2AV were retreated with antivenom; 4 patients (9%) receiving FabAV were retreated (p = 0.049). CONCLUSIONS: In the North American Snakebite Registry, late hemotoxicity was less common in rattlesnake envenomated patients treated with Fab2AV compared to FabAV.

Pediatric Methamphetamine Toxicity: Clinical Manifestations and Therapeutic Use of Antipsychotics-One Institution's Experience.

INTRODUCTION: Methamphetamine toxicity is common in the Southwest region of the United States and presents diagnostic and treatment challenges in the pediatric population. The aim of our study was to characterize signs and symptoms of methamphetamine toxicity in pediatric patients, highlighting manifestations unique to this population. Additionally, our study sought to evaluate treatment modalities, specifically antipsychotics, in this population with the intent to characterize their adverse effects. METHODS: This is a retrospective review of pediatric patients (age > 2 months ≤ 18 years) at a tertiary care pediatric hospital with ICD-9 or ICD-10 codes suggestive of stimulant exposure between September 1, 2010, and July 31, 2017. Patients with clinical manifestations of sympathomimetic toxicity and confirmation of methamphetamine on urine drug testing via GC/MS were included. Nature, source, and route of exposure along with clinical manifestations including signs, complications, treatments utilized, and adverse events related to treatment were recorded. Specifically, adverse effects following administration of antipsychotics were studied. RESULTS: Seventy-nine patients met inclusion criteria: median age 2.0 years. Typical manifestations of sympathomimetic toxicity were common, including tachycardia (93.4%), hypertension (85.7%), agitation (79.7%), and abnormal motor activity (55.8%). The prominence of gastrointestinal signs (26.3%) and unique abnormal motor activity were notable. The most common treatments were intravenous fluids (96.1%) and benzodiazepines (77.9%). Antipsychotics were administered in 40.5% of cases, with haloperidol used in the majority. No patients developed seizures, dystonia, torsades de pointes, or hyperthermia after antipsychotic administration. CONCLUSIONS: Pediatric patients with methamphetamine toxicity commonly manifest sympathomimetic signs. Antipsychotics were often used as an adjunct treatment in this cohort of patients, and no adverse events were reported. Clinicians should be aware of prominent gastrointestinal signs and abnormal motor activity and neurologic manifestations unique to pediatric patients that will assist in making the correct diagnosis in cases of suspected methamphetamine toxicity.

Diagnosis of Hepatopulmonary Syndrome in a Large Integrated Health System.

BACKGROUND & AIMS: Data on the accuracy of the diagnosis of hepatopulmonary syndrome (HPS) in cirrhosis is limited. We evaluated the clinical characteristics of patients with International Classification of Diseases (ICD) codes for hepatopulmonary syndrome (HPS) in a large integrated health system. METHODS: A retrospective review of encounters was performed of all patients with ICD-9-CM and/or ICD-10-CM diagnosis of cirrhosis and HPS from 2014-2019 in a multi-state health system. Demographics and cardiopulmonary testing closest to the time of HPS diagnosis were recorded. HPS was defined using standard criteria. RESULTS: A total of 42,749 unique individuals with cirrhosis were identified. An ICD diagnosis of HPS was found in 194 patients (0.45%), of which 182 had clinically confirmed cirrhosis. 143 (78.5%) underwent contrast-enhanced transthoracic echocardiography, and 98 (54%) had delayed shunting. Among them, 61 patients had a documented arterial blood gas, with 53 showing abnormal oxygenation (A-a gradient of >15 mm Hg). 12 were excluded due to significant pulmonary function test abnormalities and abnormal oxygenation from other cardiopulmonary diseases. Ultimately, 41 (22.5%) fulfilled the criteria for HPS. When stratifying those with an ICD code diagnosis of HPS into HPS, no HPS and indeterminate HPS groups, based on standard diagnostic criteria for HPS, we found that the confirmed HPS patients had similar complications except for less portopulmonary hypertension, worse gas exchange, less cardiopulmonary disease and were more often diagnosed in transplant centers. CONCLUSIONS: The diagnosis of HPS by ICD code is made in an extremely small subset of a sizeable cirrhotic cohort. When made, only a minority of these patients meet diagnostic criteria. Our findings highlight the need for improved education and more effective screening algorithms.

Prospective randomized controlled trial comparing cephalad migration in robotic gynecologic surgery using egg-crate foam versus the Pink Pad®.

The objectives of the study were to compare the cephalad migration of two patient positioning pads used in robotic gynecologic surgery and to determine if any correlation exists between cephalad movement and time in Trendelenburg position or body mass index. This was a prospective randomized controlled open-label trial (Canadian Task Force classification I). Sixty women undergoing robotic-assisted laparoscopic gynecologic surgery were randomized to the Pink Pad® system or egg-crate foam pre-operatively. Patients were placed under general anesthesia and then positioned in dorsal lithotomy. The locations of the iliac crest, acromion process, and buttock were marked on the table before and after surgery to calculate cephalad migration during surgery. The primary outcome was centimeters of cephalad migration at the three anatomic landmarks. Comparing the Pink Pad® (n = 24) to the egg-crate group (n = 26) revealed similar mean cephalad migration at the iliac crest (4.8 cm vs 4.3 cm, p = 0.56) and the shoulder (4.6 cm vs 3.9 cm, p = 0.39), and less cephalad migration at the buttock (median 3.0 cm vs 2.0 cm, p = 0.041). The total time in Trendelenburg was not correlated with cephalad migration at any anatomic landmark. Body mass index was positively correlated with cephalad migration only at the iliac crest (p = 0.032) regardless of pad type. The egg-crate foam resulted in less cephalad migration at all anatomic sites and significantly less migration at the buttocks compared to the Pink Pad®. This suggests that the less-costly egg-crate foam is noninferior to the Pink Pad® system and trends at superiority.

The Effect of 4-Methylpyrazole on Oxidative Metabolism of Acetaminophen in Human Volunteers.

INTRODUCTION: Acetaminophen (APAP) is commonly ingested in both accidental and suicidal overdose. Oxidative metabolism by cytochrome P450 2E1 (CYP2E1) produces the hepatotoxic metabolite, N-acetyl-p-benzoquinone imine. CYP2E1 inhibition using 4-methylpyrazole (4-MP) has been shown to prevent APAP-induced liver injury in mice and human hepatocytes. This study was conducted to assess the effect of 4-MP on APAP metabolism in humans. METHODS: This crossover trial examined the ability of 4-MP to inhibit CYP2E1 metabolism of APAP in five human volunteers. Participants received a single oral dose of APAP 80 mg/kg, both with and without intravenous 4-MP, after which urinary and plasma oxidative APAP metabolites were measured. The primary outcome was the fraction of ingested APAP excreted as total oxidative metabolites (APAP-CYS, APAP-NAC, APAP-GSH). RESULTS: Compared with APAP alone, co-treatment with 4-MP decreased the percentage of ingested APAP recovered as oxidative metabolites in 24-hour urine from 4.48 to 0.51% (95% CI = 2.31-5.63%, p = 0.003). Plasma concentrations of these oxidative metabolites also decreased. CONCLUSIONS: These results show 4-MP effectively reduced oxidative metabolism of APAP in human volunteers ingesting a supratherapeutic APAP dose. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03878693.

Peanut ball for decreasing length of labor: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Prolonged length of labor is associated with increased maternal and neonatal complications. Therefore, great attention has been given to interventions aimed at reducing the length of labor. One such intervention is the peanut ball, a large elongated exercise ball placed between a woman's legs during labor. OBJECTIVE: The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the effect of the use of peanut ball in reducing length of labor. STUDY DESIGN: Data sources: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched from inception until January 2019. SELECTION CRITERIA: Selection criteria included RCTs of laboring women with singleton gestations in cephalic presentation at term (≥37weeks) who were randomized to either use of peanut ball or control group (no peanut ball). DATA COLLECTION AND ANALYSIS: Four trials with 648 nulliparous and multiparous women in spontaneous or induced labor were identified and included. 330 women were randomized to the intervention (peanut ball between the knees during labor) and 318 women to the control. Summary measures were reported as mean difference (MD) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. The primary outcome was total length of labor. PROSPERO Registration Number: CRD42018082438 RESULTS: Total length of labor was 79min shorter in the peanut ball group, but this was not significant (MD -79.1 min, 95% CI -204.9, 46.7). Peanut ball use showed trends toward higher incidence of spontaneous vaginal deliveries (RR 1.1, 95% CI 1.0, 1.2) and lower incidence of cesarean deliveries (RR 0.8, 95% CI 0.6, 1.0). CONCLUSIONS: Peanut ball use was not associated with a significant decrease in total length of labor. Since there were trends toward reductions in length of labor, an increased incidence in spontaneous vaginal deliveries, and lower incidence of cesarean deliveries, more research is needed.

The Relationship Between Circulating Acetaminophen-Protein Adduct Concentrations and Alanine Aminotransferase Activities in Patients With and Without Acetaminophen Overdose and Toxicity.

INTRODUCTION: Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose. METHODS: We measured serial levels of serum APAP-CYS and ALT activities in 500 overdose patients in whom APAP toxicity was suspected on inpatient admission, but who were then classified at time of discharge and before results of APAP-CYS concentrations were available into three groups: 1) definite APAP group; 2) definitely not APAP group; and 3) indeterminate group. Subjects in the definite and definitely not APAP groups were selected in whom a plasma ALT activity was measured within ± 4 h of a serum APAP-CYS concentration. Regressions with correlation coefficients between APAP-CYS and ALT were calculated for repeat measures in the 335 subjects (908 blood samples) in the definite APAP group and 79 subjects (231 samples) in the definitely not APAP group, with an emphasis on APAP-CYS concentrations and calculation of 95% prediction intervals when ALT was ≥ 1000 IU/L. RESULTS: A strong correlation was found between APAP-CYS and ALT in the definite APAP group over all ALT activities (r = 0.93, p < 0.001; N = 335), and when ALT was > 1000 IU/L (r = 0.82, p < 0.001, N = 144). In the 79 definitely not APAP subjects, no significant correlation was found when ALT exceeded 1000 IU/L (r = 0.04; p = 0.84, N = 32). All subjects in the definitely not APAP group displayed APAP-CYS concentrations < 3 µM. In definitely not APAP subjects, the great majority of APAP-CYS levels were below the 95% prediction interval for APAP-CYS concentrations in definite APAP group subjects when ALT was ≥ 1000 IU/L. However, some definitely not APAP group subjects who had ingested non-toxic doses of APAP displayed APAP-CYS concentrations as high as 2.8 µM in the face of ALT elevation from ischemic hepatitis. CONCLUSION: The interpretation of serum APAP-CYS concentrations must always be made in light of detailed clinical information and the population being tested, especially because of some overlap in APAP-CYS levels in subjects with and without APAP toxicity.

Pharmacists Providing Palliative Care Services: Demonstrating a Positive Return on Investment.

Objective: To establish a return on investment (ROI) for a pharmacist position on a hospital-based palliative care (PC) team. Background: Utilizing a pharmacist to provide PC services is often overlooked as a solution to physician shortages. Integration of a pharmacist into PC teams yields a favorable ROI. Methods: A 16-month retrospective review comparing PC patients at two hospitals with consultative PC teams. The PC teams at the two facilities had identical full-time equivalent team members, except for a PC pharmacist at Facility 1. The PC pharmacist's ROI was calculated based on cost savings created by utilizing the PC pharmacist as a physician extender and costs attributable to preventable adverse drug events (pADEs) identified by the PC pharmacist. Results: An annual ROI of 1.2 to 2.9 million dollars was calculated, $125,760 from physician time saved and $1.1-2.8 million dollars from pADEs. A statistically significant difference in rates of pADEs was realized between the PC pharmacist and non-PC pharmacists at Facility 1 as well as between pharmacists at Facility 1 (PC pharmacist and non-PC pharmacists) and pharmacists at Facility 2 (non-PC pharmacists). Conclusion: A PC pharmacist's unique qualifications and perspective contribute to the value of care provided to PC patients. A favorable ROI that exceeds a pharmacist's annual salary was demonstrated in this analysis.

Comparison of Antivenom Dosing Strategies for Rattlesnake Envenomation.

OBJECTIVES: This study compares maintenance with clinical- and laboratory-triggered (as-needed [PRN]) antivenom dosing strategies with regard to patient-centered outcomes after rattlesnake envenomation. DESIGN: This is a retrospective cohort study of adult rattlesnake envenomations treated at a regional toxicology center. Data on demographics, envenomation details, antivenom administration, length of stay, and laboratory and clinical outcomes were compared between the PRN and maintenance groups. Primary outcomes were hospital length of stay and total antivenom used, with a hypothesis of no difference between the two dosing strategies. SETTING: A single regional toxicology center PATIENTS:: Three-hundred ten adult patients envenomated by rattlesnakes between 2007 and 2014 were included. Patients were excluded if no antivenom was administered or for receiving an antivenom other than Crofab (BTG International, West Conshohocken, PA). INTERVENTIONS: This is a retrospective study of rattlesnake envenomations treated with and without maintenance antivenom dosing. MAIN RESULTS: One-hundred forty-eight in the maintenance group and 162 in the PRN group were included. There was no difference in demographics or baseline envenomation severity or hemotoxicity (32.7% vs 40.5%; respectively; p = 0.158) between the two groups. Comparing the PRN with the maintenance group, less antivenom was used (8 [interquartile range, 6-12] vs 16 [interquartile range, 12-18] vials, respectively; p < 0.001), and hospital length of stay was shorter (27 hr [interquartile range, 20-44 hr] vs 34 hr [interquartile range, 24-43 hr], respectively; p = 0.014). There were no differences in follow-up outcomes of readmission, retreatment, or bleeding and surgical complications. CONCLUSIONS: Hospital length of stay was shorter, and less antivenom was used in patients receiving a PRN antivenom dosing strategy after rattlesnake envenomation.

Human Plant Exposures Reported to a Regional (Southwestern) Poison Control Center Over 8 Years.

BACKGROUND: There is little published data about human plant exposures reported to US poison control centers (PCCs). METHODS: A retrospective chart review of all reported plant exposures to a single regional PCC between January 1, 2003 and December 31, 2010 was done to understand better the characteristics of plant exposure cases. Specific generic plant codes were used to identify cases. Recorded variables included patient demographics, plant involved, exposure variables, symptoms, management site, treatments, and outcome. Univariate and multivariate regression was used to identify outcome predictors. RESULTS: A total of 6492 charts met inclusion criteria. The average age was 16.6 years (2 months-94 years); 52.4% were male. The most common exposure reason was unintentional (98%), and the majority (92.4%) occurred at the patient's home. Ingestions (58.3%) and dermal exposures (34.3%) accounted for most cases. Cactus (27.5%), oleander (12.5%), Lantana (5.7%), and Bougainvillea (3.8%) were most commonly involved. Symptoms developed in 47.1% of patients, and were more likely to occur following Datura (66.7%), and Morning Glory or Milkweed (25% each) exposures. Almost 94% of patients were managed onsite (home) and only 5.2% involved evaluation in a health care facility (HCF). Only 37 (0.6%) patients required hospital admission, and 2.9% of cases resulted in more than minimal effects. Exposures resulting in more than minimal clinical effects were predicted by several variables: abnormal vital signs (OR = 35.62), abnormal labs (OR = 14.87), and management at a HCF (OR = 7.37). Hospital admissions were increased for patients already at a HCF (OR = 54.01), abnormal vital signs (OR = 23.28), and intentional exposures (OR = 14.7). CONCLUSION: Plant exposures reported to our poison control center were typically unintentional ingestions occurring at home. Most patients were managed onsite and few developed significant symptoms.

Clinical predictors of tissue necrosis following rattlesnake envenomation.

BACKGROUND: Rattlesnake envenomation (RSE) causes edema, hemotoxicity and tissue necrosis. Necrosis may result in permanent disability. OBJECTIVE: To study patient-related factors associated with tissue necrosis after Crotalus envenomation. METHODS: Prospective cohort study of patients admitted to the Medical Toxicology service with diagnosis of RSE between April 2011 and November 2014. Inclusion criteria were age ≥18 years and upper extremity (UE) envenomation site. Primary outcome was tissue necrosis, including dermonecrosis, manifesting as bullae. Secondary outcome was amputation. RESULTS: 77 subjects, age 18 to 88 years, met inclusion criteria. Rattlesnake species was unknown in most cases. All received Fab antivenom. 62 (82%) had a digital envenomation. 31 (40.3%) had necrosis. Necrotic area ranged from 0.1 cm2 to 14 cm2. Procedural interventions, (superficial debridement, dermotomy, surgical exploration, and operative debridement of devitalized tissue) occurred in 25 (32.5%). Five (6.5%) underwent dermotomy and 6 (7.8%) operative debridement. No amputations were performed. Patients with cyanosis on presentation had increased risk of developing necrosis (11/12; RR 2.98 95% CI 1.99-4.46). Ecchymosis on presentation was also associated with increased risk of necrosis (24/32; RR 4.04 95% CI 2.08-7.86). Patients with social or regular ethanol use were more likely to develop necrosis than those without (28/53; RR 4.23 95% CI 1.42-12.6). Regular cocaine use was associated with increased risk of operative debridement (4/6; RR 9.13 95% CI 2.33-35.8). A nonsignificant risk of operative debridement occurred with tobacco use (RR 1.14 95%CI 0.99-1.31 p = 0.09). Time to antivenom did not correlate with risk of necrosis. CONCLUSION: UE RSE patients who presented with cyanosis, ecchymosis or history of ethanol use were at increased risk of developing necrosis. Cocaine use was associated with increased risk of operative debridement.

Automatic analysis of the retinal avascular area in the rat oxygen-induced retinopathy model.

Purpose: The aim of this study was to create an algorithm to automate, accelerate, and standardize the process of avascular area segmentation in images from a rat oxygen-induced retinopathy (OIR) model. Methods: Within 6 h of birth, full-term pups born to Sprague Dawley rat dams that had undergone partial bilateral uterine artery ligation at embryonic day 19.5 were placed into a controlled oxygen environment (Oxycycler, BioSpherix, Parish, NY) at 50% oxygen for 48 h, followed by cycling between 10% and 50% oxygen every 24 h until day 15. The pups were then moved into room air until day 18.5. Ten lectin-stained retinal flat mounts were imaged in montage fashion at 10x magnification. Three masked human reviewers measured two parameters, total retinal area and peripheral avascular area, for each image using the ImageJ freehand selection tool. The outputs of each read were measured as number of pixels. The gold standard value for each image was the mean of the three human reads. Interrater agreement for the measurement of total retinal area, avascular area, and percent avascular area was calculated using type A intraclass correlation coefficients (ICCs) with a two-way random effects model. Automated avascular area identification (A3ID) is a method written in ImageJ Macro that is intended for use in the Fiji (Fiji is Just ImageJ) image processing platform. The input for A3ID is a rat retinal image, and the output is the avascular area (in pixels). A3ID utilizes a random forest classifier with a connected-components algorithm and post-processing filters for size and shape. A separate algorithm calculates the total retinal area. We compared the output of both algorithms to gold standard measurements by calculating ICCs, performing linear regression, and determining the Dice coefficients for both algorithms. We also constructed a Bland-Altman plot for A3ID output. Results: The ICC for percent peripheral avascular/total area between human readers was 0.995 (CI: 0.974-0.999), with p<0.001. The ICC between A3ID and the gold standard was calculated for three image parameters-avascular area: 0.974 (CI: 0.899-0.993), with p<0.001; total retinal area: 0.465 (CI: 0.0-0.851), with p=0.001; and the percent peripheral avascular/total area: 0.94 (CI: 0.326-0.989), with p<0.001. In the linear regression analysis, the slope for prediction of the gold standard percent peripheral avascular/total area from A3ID was 0.98, with R2=0.975. A3ID and the total retinal area algorithm achieve an average Dice coefficient of 0.891 and 0.952, respectively. The Bland-Altman analysis revealed a trend for computer underestimation of the peripheral avascular area in images with low peripheral avascular area and overestimation of peripheral avascular area in images with large peripheral avascular areas. Conclusions: A3ID reliably predicts peripheral avascular area based on rat OIR retinal images. When the peripheral avascular area is particularly high or low, hand segmentation of images may be superior.

Clinical Presentation and Outcomes Associated with Different Treatment Modalities for Pediatric Bark Scorpion Envenomation.

INTRODUCTION: Scorpion envenomation is potentially life-threatening and affects children in the Southwestern USA. An FDA-approved antivenom is available, but its high cost has led to use of off-label antivenom dosing or supportive care alone as alternatives to FDA-recommended dosing. This study sought to determine whether treatment approach influences outcomes in envenomated children. METHODS: A retrospective cohort study of children with grade III or IV scorpion envenomation evaluated in Phoenix Children's Hospital ED between September 1, 2011, and March 31, 2014. Patients were grouped based on treatment: group 1, supportive care only; group 2, FDA-recommended dosing (3-vial initial dose); group 3, "off label" dosing (1-2 vial initial dose). Primary outcomes were ED length of stay and hospital admission. Secondary outcomes were mechanical ventilation and aspiration pneumonia. RESULTS: One hundred fifty-six patients were included with 58 patients in group 1, 16 patients in group 2, and 82 patients in group 3. Group 1 was significantly older than the antivenom groups (p < 0.001), and group 2 was younger than group 3 (p = 0.024). Envenomation grade was also different, with group 1 having fewer grade IV then groups 2 and 3 (p < 0.001). Three percent of group 1, 56 % of group 2, and 28 % of group 3 had respiratory distress (p < 0.001). ED LOS was not significantly different between groups. Hospital admission occurred in 3.4 % group 1, no group 2, and 8.5 % group 3 patients. Two intubations and two aspirations occurred in group 3. CONCLUSIONS: In this study, clinical presentation appeared to influence treatment. Groups that received antivenom had a higher envenomation grade than the group that received supportive care. The FDA-recommended dosing group was younger and had more respiratory distress than those treated with initial doses of 1-2 vials. Outcomes were not significantly different between groups. Prospective studies may identify the ideal population for each treatment approach.

Impact of a Standardized Treatment Guideline for Pediatric Iatrogenic Opioid Dependence: A Quality Improvement Initiative.

OBJECTIVES: To determine whether utilization of a hospital-based clinical practice guideline for the care of pediatric iatrogenic opioid dependence (IOD) would promote a decrease in opioid exposure and improve management of opioid abstinence syndrome (AS). METHODS: This study is a retrospective chart review of critically ill patients from a tertiary care children's hospital. Inclusion criteria included mechanically ventilated patients up to 18 years of age who received continuous opioid infusions for at least 7 days and any length of methadone administration. Data on IOD patients from January 2005 to June 2010 was divided into 3 periods: baseline, phase 1, and phase 2. Primary outcome was decrease in opioid exposure, measured by methadone duration of use and any additional opioid bolus doses used in AS management. Documentation of additional opioid bolus doses was regarded as a surrogate measure of AS. Secondary outcomes included total cumulative fentanyl dose, continuous fentanyl infusion duration of use, and hospital and pediatric intensive care unit length of stay. RESULTS: There was a significant decrease in methadone duration of use in IOD patients from 15.3 ± 8.7 days at baseline to 9.5 ± 3.7 days during phase 1 (p = 0.002), to 8.1 ± 3.7 days on phase 2 (reduction not significant, p = 0.106) of this evaluation. Additional opioid bolus doses were significantly lower from baseline to phase 1 (5.5 ± 5.1 vs. 1.8 ± 2.3, p = 0.001) and from phase 1 to phase 2 (1.8 ± 2.3 vs. 0.2 ± 1.5, p = 0.003). For the remaining outcomes, differences were not observed among the evaluation periods, except for the total cumulative fentanyl dose, which was reduced from 2.8 ± 3.7 mg/kg at baseline to 1 ± 1 mg/kg only during phase 1 (p = 0.017). CONCLUSIONS: Introduction of a standardized, hospital-based clinical practice guideline for children with IOD reduced the length of exposure to opioids and improved opioid AS management.

Comparison of Prothrombin Time and Aspartate Aminotransferase in Predicting Hepatotoxicity After Acetaminophen Overdose.

Despite decades of experience with acetaminophen (APAP) overdoses, it remains unclear whether elevated hepatic transaminases or coagulopathy develop first. Furthermore, comparison of the predictive value of these two variables in determining hepatic toxicity following APAP overdoses has been poorly elucidated. The primary objective of this study is to determine the test characteristics of the aspartate aminotransferase (AST) and the prothrombin time (PT) in patients with APAP toxicity. A retrospective chart review of APAP overdoses treated with IV N-acetylcysteine at a tertiary care referral center was performed. Of the 304 subjects included in the study, 246 with an initial AST less than 1000 were analyzed to determine predictors of hepatic injury, defined as an AST exceeding 1000 IU/L. The initial AST >50 was 79.5 % sensitive and 82.6 % specific for predicting hepatic injury. The corresponding negative and positive predictive values were 95.5 and 46.3 %, respectively. In contrast, an initial abnormal PT had a sensitivity of 82.1 % and a specificity of 63.6 %. The negative and positive predictive values for initial PT were 94.9 and 30.2 %, respectively. Although the two tests performed similarly for predicting a composite endpoint of death or liver transplant, neither was a useful predictor. Initial AST performed better than the initial PT for predicting hepatic injury in this series of patients with APAP overdose.

Management of Nephrotic Syndrome in the Pregnant Patient.

Objective: To present a case series of pregnant women with nephrotic syndrome, describe maternal and fetal outcomes, and propose treatment strategies. Study Design: A retrospective cohort case review of 11 pregnant women with nephrotic syndrome was performed over 2 years. Treatment regimens and trends were recorded. Linear regression was used for continuous outcomes, and logistic regression for categorical outcomes (p<0.05). Results: On first admission, 3 of 11 patients had a serum creatinine >1.4 mg/dL; all 11 exhibited an antepartum increase in creatinine. Two required antepartum dialysis, and 3 were dialyzed postpartum. Initial mean 24-hour urine protein was 10,522 mg (2,160-36,603) and increased to 26,220 mg (4,650-49,980). Pregravid weight increased from a mean 95 kg (BMI 33.8) to 112 kg (BMI 39.9) at time of delivery. Mean antepartum and postpartum diuresis was 33.2 L (±25.8) and 5.2 L (±8.2), respectively. Mean serum albumin levels were 2 g/dL. Ten patients received intravenous diuretics and 9 received intravenous albumin. Mean gestational age at delivery was 34w 3d (30.4-38.4). Conclusion: Pregnant women with nephrotic syndrome can be managed successfully by a collaborative team of obstetricians and nephrologists with careful diuresis, repletion of albumin, and administration of anticoagulants, when necessary, to deliver a healthy, probably preterm, neonate.

Retrospective Review of Critically Ill Patients Experiencing Alcohol Withdrawal: Dexmedetomidine Versus Propofol and/or Lorazepam Continuous Infusions.

BACKGROUND: Alcohol withdrawal symptoms can be difficult to manage and may lead to an intensive care unit (ICU) admission. Patients experiencing severe alcohol withdrawal often require high doses of sedatives, which can lead to respiratory depression and the need for endotracheal intubation. Dexmedetomidine, an alpha-2 adrenoreceptor agonist, provides adequate sedation with little effect on respiratory function when compared to other sedatives. OBJECTIVE: To evaluate sedation with a continuous infusion of dexmedetomidine versus propofol and/or lorazepam in critically ill patients experiencing alcohol withdrawal. METHODS: A retrospective chart review was conducted on ICU admissions between March 2002 and April 2009 for alcohol withdrawal patients who necessitated treatment with a continuous infusion of dexmedetomidine, propofol, and/or lorazepam. Primary outcomes included the incidence of mechanical ventilation, length of mechanical ventilation (if applicable), and ICU and hospital length of stay. RESULTS: Fifteen patients were treated with a continuous infusion of dexmedetomidine, and 17 were treated with an infusion of propofol and/or lorazepam. Two patients (13.3%) required intubation and mechanical ventilation in the dexmedetomidine group versus 10 (58.8%) in the propofol and/or lorazepam group (P = .006). Length of stay in the ICU was 53 hours for patients treated with dexmedetomidine versus 114.9 hours in the propofol and/or lorazepam group (P = .016). Hospital length of stay was less for the dexmedetomidine group, 135.8 hours versus 241.1 hours in the propofol and/or lorazepam group (P = .008). CONCLUSIONS: Dexmedetomidine use was associated with a decrease in the incidence of endotracheal intubation when used to sedate patients experiencing alcohol withdrawal. Patients transferred to a lower level of care faster and were discharged from the hospital sooner when treated with dexmedetomidine.

Impact of a clinical pharmacist stress ulcer prophylaxis management program on inappropriate use in hospitalized patients.

PURPOSE: Appropriate utilization of stress ulcer prophylaxis should be limited to high-risk, intensive care unit (ICU) patients. However, inappropriate stress ulcer prophylaxis use among all hospitalized patients remains a concern. The purpose of this study was to evaluate the clinical and economic impact of a novel pharmacist-managed stress ulcer prophylaxis program in ICU and general ward patients. METHODS: This retrospective, pre- and poststudy design was conducted in adult ICU and general ward patients at a large academic medical center between January 1, 2011 and January 31, 2012 to compare the rates of inappropriate stress ulcer prophylaxis before and after the implementation of a pharmacist-led stress ulcer prophylaxis management program. RESULTS: A total of 1134 unique patients consisting of 16,415 patient days were evaluated. The relative reduction in the rate of inappropriate stress ulcer prophylaxis days after program implementation in ICU and general ward patients was 58.3% and 83.5%, respectively (P < .001). The rates of ICU patients inappropriately continued on stress ulcer prophylaxis upon hospital discharge in the pre- and postimplementation groups were 29.9% and 3.6%, respectively (P < .001), whereas general ward patients significantly decreased from 36.2% to 5.4% in the pre- and postimplementation groups, respectively (P < .001). Total inpatient costs associated with all stress ulcer prophylaxis administered was $20,052.70 in the pre- and $3280.49 in the postimplementation group (P < .001), resulting in an estimated cost savings of > $200,000 annually. No differences in clinical outcomes were observed. CONCLUSIONS: The implementation of a pharmacist-managed stress ulcer prophylaxis program was associated with a decrease in inappropriate acid suppression rates during hospitalization and upon discharge, as well as significant cost savings.

Medical Prevention of Barrett's Esophagus: Effects of Statins, Aspirin, Non-aspirin NSAIDs, Calcium, and Multivitamins.

BACKGROUND: Barrett's esophagus (BE) is a complication of gastroesophageal reflux disease (GERD) that is a precursor to esophageal adenocarcinoma. There is limited information regarding whether medications can reduce the risk of developing BE. AIM: We analyzed medical records at a large veterans hospital to determine the effects of statins, aspirin, non-aspirin NSAIDs, calcium, or multivitamins on the risk of developing BE. METHODS: In this retrospective case-control study, 250 patients with biopsy-confirmed Barrett's esophagus were compared with 250 controls with acid-peptic symptoms but no endoscopic BE. Medication histories were reviewed for the use of the above substances prior to endoscopic evaluation. Logistic and linear regression was used to determine predictors of the outcomes. RESULTS: Mean age at diagnosis was significantly older in the Barrett's population compared with controls (61.2 vs. 56.7 years, P < 0.001), with no difference in mean BMI (29.1 vs. 29.0, respectively). On multivariate analysis, independently significant factors for risk of BE were found with multivitamins (OR 0.41, P = 0.001), statins (OR 0.53, P = 0.003), age (OR 1.033/year, P = 0.001), and Hispanic ethnicity (OR 0.38, P = 0.007). Furthermore, statin use was associated with less long-segment (3 cm or longer) BE and was inversely correlated with continuous BE length. CONCLUSIONS: GERD patients with BE are less likely to use multivitamins and statins, as well as less likely to be of Hispanic ethnicity. Additionally, statins were inversely associated with BE length. Prospective studies of this topic are indicated.