Oral Diphenhydramine Research Articles

Psilocybin for alcohol use disorder: Rationale and design considerations for a randomized controlled trial

Several lines of evidence suggest that classic psychedelics (5-HT2A receptor agonists or partial agonists) such as psilocybin might facilitate behavior change in individuals with substance use disorders. We conducted a multi-site, double-blind, randomized controlled trial (RCT) to assess the effects of psilocybin-assisted psychotherapy in alcohol-dependent volunteers. In addition to a structured 12-week psychotherapy platform, participants (n = 96) were randomly assigned (1:1) to receive either oral psilocybin or an active placebo (oral diphenhydramine) in each of two dosing sessions (at weeks 4 and 8). Initial doses were 25 mg/70 kg psilocybin or 50 mg diphenhydramine, which could be increased in the second session depending on initial response. The psychotherapy platform combined evidence-based, manualized therapy for alcohol dependence with a supportive context for the dosing sessions. All participants were followed in the RCT through week 36. At the end of the RCT, participants who still met safety criteria were offered an open-label psilocybin session. Data collected at screening, baseline and throughout the study included: demographics, measures of alcohol use, subjective response to psilocybin and diphenhydramine, and safety measures. The primary outcome was the proportion of heavy drinking days during the 32 weeks after the first dosing session (i.e., between week 4 and week 36). Secondary outcomes included safety, additional measures of drinking (e.g., abstinence, drinking days, etc.), craving, self-efficacy, and acute effects. We will also explore moderators and mediators of the primary outcome. The primary outcomes will be published elsewhere. In this paper, we describe the protocol and rationale for our design decisions.

S2113 Rare Case of PEG-Based Bowel Prep Severe Allergic Reaction

Introduction: Bowel preps are commonly Polyethylene Glycol (PEG)-based and allergic reactions are rare and not commonly severe. Its chemical formula allows for it to be soluble in water with minimal gastrointestinal absorption, which increases water retention in the colon. This component’s wide scale adoption is due to the ability to be manufactured with varying tonicities, typically isotonic and hypotonic. In rare cases patients may be allergic to these chemicals, and lead to severe symptoms such as dyspnea, facial flushing, urticaria, and vomiting. We present a rare case of recurrent severe allergic reaction to PEG-based bowel preparations. Case Description/Methods: An asymptomatic 60-year-old White man presented for colon cancer screening and intermittent GI bleeding. A PEG-based pill preparation was prescribed to the patient for his colonoscopy. Shortly after initiating his prep, he complained of difficulty tolerating the prep and developed generalized pruritus and urticaria. He was advised to stop the bowel prep immediately and subsequently responded with conservative treatment with oral Diphenhydramine. In light of this adverse reaction, he was prescribed an alternative PEG-based liquid prep, however, the same allergic reaction occurred shortly after initiating the preparation. A decision was thus made to use a non-PEG based bowel prep on his third attempt. The patient was able to tolerate the prescribed prep without incident and did not have any of the previous symptoms. As a result, the patient was able to complete his colonoscopy successfully. Discussion: Severe allergic reactions to Polyethylene Glycol (PEG)-based bowel preparations are quite rare and can be associated with symptoms such as dyspnea, facial flushing, urticaria, and vomiting. Due to the common use of such preps, such adverse reactions can not only be clinically concerning but also inconvenient as multiple similar preparations may be tried, as in the case of our patient. In light of this, alternative non-PEG based bowel preps should be considered if a severe reaction or anaphylaxis is seen with an initial PEG-based preparation. Non-PEG based bowel preps such as saline-based preps can provide an effective alternative for such patients. Gastroenterologists should be aware of this rare, yet potentially high risk adverse reaction to PEG-based preparations and consider an alternative non-PEG based preparation as a first-line option after initial adverse reaction to mitigate potential recurrent risk.

Pharmacokinetics of diphenhydramine following single-dose intravenous and oral administration in non-fasted adult horses.

Diphenhydramine is an H1 receptor antagonist used to control urticaria and other allergic signs caused by type I hypersensitivity reactions in horses (Equus caballus). Limited studies have been conducted on pharmacokinetics of this drug in horses, with no studies involving oral formulations. Our study investigated pharmacokinetics of an oral diphenhydramine formulation compared to intravenous administration in non-fasted adult horses. Six healthy horses underwent a single administration of three different doses of diphenhydramine (1mg/kg intravenously, 1mg/kg intragastrically, and 5mg/kg intragastrically) with a two-week washout period between doses. Bioavailability of intragastric diphenhydramine was less than one percent and six percent for 1mg/kg and 5mg/kg intragastric doses, respectively. This poor bioavailability is similar to what is reported in dogs. Two of six horses experienced transient side effects after intravenous diphenhydramine administration, emphasizing the need for determining therapeutic plasma levels in efforts to determine the lowest effective dose minimizing risk of adverse effects. The main conclusion of our study was that oral diphenhydramine at doses up to 5mg/kg are unlikely to achieve therapeutic plasma levels in adult horses.

DRESS syndrome in the setting of oxacillin therapy\u2014a call for better patient preparedness: a case report

BackgroundDrug reaction with eosinophilia and systemic symptoms syndrome is a rare but severe and potentially life-threatening hypersensitivity reaction, with significant morbidity and mortality. The clinical presentation of drug reaction with eosinophilia and systemic symptoms may include extensive skin rash, fever, lymphadenopathy, internal organ involvement, eosinophilia, and atypical lymphocytosis, most commonly due to drug-induced reaction. Our case is a rare occurrence of drug reaction with eosinophilia and systemic symptoms syndrome in the setting of oxacillin therapy.Case presentationA 55-year-old Caucasian male presented to the emergency department on account of acute onset, 2-day history of generalized pruritic rash with associated fever, occurring 3 weeks after commencing therapy with intravenous oxacillin for methicillin-sensitive Staphylococcus aureus bacteremia. He had no known drug allergies. Two days prior to hospitalization, he had a telehealth visit with the infectious diseases specialist on account of his rash, and was recommended to use oral diphenhydramine. However, with the onset of fever and persistence of his rash, he was advised to discontinue the oxacillin and present to the emergency department. On examination, he was febrile at 101.2 °F and had a generalized blanchable maculopapular and morbilliform rash involving the face, trunk, upper and lower extremities, but sparing the palms, soles, and oral mucosa. He had palpable nontender lymph nodes in the cervical and inguinal regions bilaterally. Laboratory studies revealed atypical lymphocytosis, eosinophilia, neutrophilia, and elevated serum transaminases. He was started on intravenous diphenhydramine and admitted to the in-patient medical service. On the second day of hospitalization, his fever resolved. However, his rash was persistent and generalized, as well as elevated transaminases and an abnormal cell count on the second day of hospitalization. To complete his 6-week course of antibiotics for methicillin-sensitive Staphylococcus aureus bacteremia, he was switched to an alternative therapy with cefazolin, and he was scheduled for weekly follow-up assessments following hospital discharge.ConclusionsHealthcare providers should increasingly be aware of the significant morbidity and mortality attributable to drug reaction with eosinophilia and systemic symptoms syndrome and the potential medications which may incite such life-threatening reactions. Early recognition of drug reaction with eosinophilia and systemic symptoms syndrome and prompt institution of management strategies can promote improved clinical outcomes. Enhanced patient–provider communication strategies should be implemented to better prepare patients for the likelihood of such drug reactions, with the goal of improving patient-centered care and adherence with treatment strategies.

Comparison of the effect of oral diphenhydramine and midazolam on sedation of children

Objectives: The aim of this study was to compare the effect of diphenhydramine and midazolam on sedation of children. Methods: This clinical trial was performed on children aged 1 to 7 years who referred to the emergency department for diagnostic radiology. Patients were randomly divided into two groups of midazolam and diphenhydramine. Then, 30 minutes before the start of the procedure, 0.5 mg /kg was given to the midazolam group and 0.5 cc /kg to the diphenhydramine group. If sedation occurred, the child was separated from the parents and transferred to a diagnostic procedure. After performing the intended diagnostic procedure, the information sheet was completed and the patient's vital signs were checked again. The data were then analyzed by SPSS version 19 software. Results: A total of 74 patients were included in the study. There was no significant difference between the two groups in terms of age and gender (P = 0.89; P = 0.32). The mean sedation in the midazolam and diphenhydramine groups was 1.02 and 1.59 years, respectively. A significant difference was found between the two groups in terms of sedation (P = 0.04), where a greater effect of diphenhydramine on sedation was observed. Conclusion: The findings showed that the use of diphenhydramine resulted in effective sedation for children. Due to the fact that the main problem with midazolam is its bitter taste, which makes children reluctant to eat it, the use of diphenhydramine can be recommended.

Biphasic anaphylaxis after first dose of messenger RNA coronavirus disease 2019 vaccine with positive polysorbate 80 skin testing result

Biphasic anaphylaxis after first dose of messenger RNA coronavirus disease 2019 vaccine with positive polysorbate 80 skin testing result

Assessment Of Hypersensitivity Reactions and Feasibility Of a 60 Minute Rapid Infusion Rituximab Protocol At a Comprehensive Cancer Center

IntroductionRituximab (R) is a chimeric monoclonal antibody with approved indications for non-hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Infusion reactions among patients with NHL are common during the first infusion (incidence of 77%), but decrease with subsequent infusions. Consequently, infusions have been gradually titrated, which may take more than three hours for completion depending on dose and tolerability. However, emerging data suggest that rapid infusion protocols may be safe for patients who receive the first dose with minimal infusion toxicity. MethodsThe purpose of this study was to assess the feasibility of a rapid infusion R protocol in a comprehensive cancer center's outpatient infusion center. The primary outcome measure was the incidence of grade 3 and 4 hypersensitivity reactions during a 60 minute infusion protocol of R in patients with B-cell malignancies. Secondary objective included infusion time savings of a 60 minute infusion of R versus a standard titration schedule, as well as nursing satisfaction. Patients were enrolled in this prospective, single institution, single arm study which was approved by the investigational review board. Inclusion criteria included age >18 years, diagnosis of indolent or intermediate grade B-cell malignancy, second R infusion within 3 months of first infusion, and planned outpatient treatment with a regimen including R therapy at a dose of 375mg/m2. Patients were excluded for diagnosis of an aggressive lymphoma histology, absolute lymphocyte count > 10 x 103/µL, enrollment on another clinical trial, allergy to murine-containing medications, exposure to R (<6 months from first dose) prior to enrollment in this study, or grade 3 or 4 hypersensitivity reaction during first R infusion. All patients received the first dose of R by the standard titration schedule as described in the package insert. The investigational protocol was instituted for the second R administration. The infusion began at 100mg/hr administered over 15 minutes and the remaining dose was given over 45 minutes. All patients received 50mg of oral diphenhydramine and 650mg of oral acetaminophen as premedication. To calculate time savings between rapid infusion and standard titration, each patient served as their own control. Nursing data collection included monitoring vitals every 15 minutes (blood pressure, heart rate, temperature, respiratory rate), start and stop times of R infusion, description and grade of hypersensitivity reactions, administration of rescue medications during infusion, and survey assessment of nursing satisfaction. ResultsFrom October 2010 to April 2013, 52 patients were enrolled to the study. Fifty received rapid infusion over 60 minutes during the second R administration. The 2 patients who did not continue on study were deemed ineligible. Patient 1 expired secondary to disease progression after signing consent and patient 2 experienced a grade 3 reaction following end of first infusion. The median age was 63 years (19-85) with 60% female. Chemotherapy regimens included: R-cyclophosphamide, doxorubicin, vincristine, prednisone (RCHOP, n = 19), single-agent R (n = 14), R-bendamustine (BR, n=7), R-cyclophosphamide, vincristine, prednisone (RCVP, n=4), R-gemcitabine, oxaliplatin (RGEMOX, n=3), R-fludarabine, cyclophosphamide (FCR, n=1), R-pentostatin, cyclophosphamide (PCR, n=1) and R-bortezomib (n=1). The rate of infusion related reactions (all grades) observed with the rapid infusion protocol was 0% (1-sided 97.5% CI 0-7.1%). The mean time for the rapid R infusion was 62.4 (95% CI 61.2-63.6) minutes. When compared to the standard second dose infusion recommendations, a mean time of 94.2 (95% 90-98.4) minutes was saved with rapid infusion. Post infusion nursing surveys demonstrated 100% satisfaction with administration of rapid infusion over standard titration practice. ConclusionsA 60 minute rapid rituximab infusion can be safely administered in an outpatient infusion center. The faster infusion allows for less resource utilization and increased nursing satisfaction. Disclosures:No relevant conflicts of interest to declare.

Anaphylactic Reaction to Dulaglutide: A Glucagon Like Peptide- 1 Receptor Agonist

Introduction: The development of Glucagon like peptide-1 (GLP-1) receptors agonists represents an important advancement in the management of type 2 diabetes. The long-acting GLP-1 receptor agonists improve glycemic control, promote weight loss. Anaphylaxis to GLP-1 receptor agonists and mainly Dulaglutide is a rare but serious side effect. We report a patient with Type 2 DM who was recently started on Dulaglutide and started to experience systemic hypersensitivity reactions that required discontinuing the medication and inpatient hospitalization. Case: A 53-Year-old Caucasian female with past medical history of type 2 DM on Metformin presented to the ED with sudden onset of sporadic itchy rash on the lip and chin associated with lip swelling within one hour of her first injection of Dulaglutide. She denied difficulty breathing, rash or pruritus on any other part of the body. She denied any food allergies. The patient used two tablets of Oral Diphenhydramine 25 mg with minimal improvement in her symptoms which warrant her to come to the ED. On arrival, she was Afebrile with a HR 97 beats/minute, a BP of 105/58 mm of Hg and a RR of 17 breaths/minute. The rash was blotchy, non- tender, more evident on the upper lip as compared to the lower lip. Lab results showed WBC count of 11 k/uL with basophils of 2% and HbA1c 8.6%. She was treated for her allergic reaction with Intramuscular injection of Epinephrine 0.3mg, Intravenous Dexamethasone 6mg and Intravenous Diphenhydramine 25mg. She was then transferred to the observation unit for monitoring. Her home metformin 500mg two times a day was continued. After 48 hours, the patient’s symptoms were improved and she was discharged home. She was advised to follow up with her PCP and endocrinologist and stop Dulaglutide. Discussion: GLP-1 receptor agonists are commonly used currently in the management of DM due to their beneficial effect in controlling blood glucose as compared to other diabetic medications. Rarely, a potentially life-threatening reaction, such as anaphylactic reactions have been documented with GLP-1 receptor agonist. Systemic allergic reaction to GLP-1 Agonist Exenatide has been reported in the literature. Our patient had anaphylactic reaction after using Dulaglutide. The mechanism of action of anaphylaxis in GLP-1 receptor agonists is thought to be related to IgE mediated and the immune response was demonstrated by basophil activation.

Use of a Beta-Lactam Graded Challenge Process at an Academic Medical Center

Background: A penicillin allergy guidance document containing an algorithm for challenging penicillin allergic patients with β-lactams was developed by the antimicrobial stewardship program (ASP). As part of this algorithm, a “graded challenge” order set was created containing antimicrobial orders and safety medications along with monitoring instructions. The process is designed to challenge patients at low risk of reaction with infusions of 1% of the target dose, then 10%, and finally the full dose, each 30 minutes apart. We evaluated outcomes from the order set. Methods: Orders of the graded challenge over 17 months (March 2018 through July 2019) were reviewed retrospectively. Data were collected on ordering and outcomes of the challenges and allergy documentation. Use was evaluated based on ASP-recommended indications: history of IgE-mediated or unknown reaction plus (1) no previous β-lactam tolerance and the reaction occurred &gt;10 years ago, or (2) previous β-lactam tolerance, now requiring a different β-lactam for treatment. Only administered challenges were included and descriptive statistics were utilized. Results: Of 67 orders, 57 graded challenges were administered to 56 patients. The most common allergies were penicillins (87.7%) and cephalosporins (38.6%), with the most common reactions being unknown (41.7%) or hives (22%). The most common antibiotics challenged were ceftriaxone (43.9%), cefepime (21.1%), and cefazolin (5.3%). Antibiotics given prior to challenge included vancomycin (48.2%), fluoroquinolones (35.7%), carbapenems (21.4%), aztreonam (19.6%), and clindamycin (12.5%). The median duration of challenged antibiotic was 6 days. The infectious diseases service was consulted on 59.6% of challenges and 75.4% of challenges were administered in non-ICU settings. There was 1 reaction (1.8%) involving a rash with the second infusion, which was treated with oral diphenhydramine and had no lasting effects. Based on indications, 80.7% of challenges were aligned with ASP guidance criteria. The most common use outside of these criteria was in patients without IgE-mediated reactions (10.5%). Most of these had minor rashes and could have received a full dose of a cephalosporin. Allergy information was updated in the electronic health record after 91.2% of challenges. Conclusions: We demonstrated the utility of a graded challenge process at our academic medical center. It was well tolerated, ordered frequently by noninfectious diseases clinicians, administered primarily in non-ICU settings, and regularly resulted in updated allergy information in the medical record. With many patients initially receiving broad-spectrum antibiotics with high costs or increased rates of adverse effects, graded challenges can potentially prevent the use of suboptimal therapies with minimal time and resource investment.Funding: NoneDisclosures: Scott Bergman reports a research grant from Merck.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis.

Purpose: To compare the incidence of oversedation between oral and parenteral diphenhydramine therapy for treatment of opioid-induced pruritus in patients with sickle cell disease vaso-occlusive crisis (SCD VOC). Methods: This retrospective, single-center, cohort study included patients greater than or equal to 18 years old with sickle cell disease admitted for vaso-occlusive crisis who received either intravenous or oral diphenhydramine for opioid-induced pruritus. Patients were identified through ICD-9 and ICD-10 codes from June 1, 2016 through July 1, 2017. Rates of oversedation were compared between the 2 formulations. Secondary endpoints included length of stay, amount and duration of diphenhydramine, rate of acute chest and indication for IV therapy. Results: Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups. Twenty-nine percent of patients in the IV diphenhydramine group experienced oversedation (12/42) versus 13% in the oral diphenhydramine group (2/15, P = .312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs 1.20; P = .005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs 10.67, 10.0; P = .003). Conclusion: While there was no statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine had more frequent admissions and a longer length of stay. Clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration.

Progressive Rash In A High School Basketball Athlete

HISTORY: A 16 year old female high school basketball player presented to the athletic training room with a rash on the bilateral lower extremities. It was first noticed 1 week prior to presentation and had progressed from the feet and ankles proximally to the upper thighs. She stated that she initially had right ankle pain but at presentation felt her left knee was particularly swollen and painful. She denied any significant itching related to the rash but felt her legs were swollen and heavy. She denied any specific joint trauma and had been participating in her usual physical activities. She endorsed that she was currently recovering from an upper respiratory viral illness that occurred prior to the appearance of the rash. She had tried taking oral diphenhydramine for the rash which did not help. PHYSICAL EXAMINATION: She was in no acute distress. Nasal congestion and cough were noted. The legs were diffusely swollen from the ankles to the proximal third of the thighs bilaterally with scattered, non-blanching and non-tender purpuric lesions. There was non-specific tenderness to palpation about the left knee without warmth. It was difficult to assess for a knee effusion as there was significant soft tissue swelling. Knee flexion range of motion was 0 to 150 degrees, pain-free and flexion and extension strength was 5/5. Ligamentous structures of the knees were intact. Sensation to light touch of the bilateral lower extremities was intact. She reported pain in the left knee with gait but was not observed as having a limp. Balance was intact. DIFFERENTIAL DIAGNOSIS: 1)Septic arthritis 2)Transient synovitis 3)Lyme disease 4)IgA Vasculitis (formerly known as Henoch-Schnolein Purpura) 5)Coagulopathy 6)Dermatologic hypersensitivity TESTS AND RESULTS: The patient was sent to the emergency department for further evaluation. Blood pressure was 116/69, pulse was 90, respiration rate was 19 breaths per minute with 100% oxygen saturation, and temperature was 97.5oF. A complete blood count showed normal platelets and no leukocytosis, while a basic metabolic panel showed normal renal function. A urinalysis showed trace blood and left lower extremity vascular ultrasound was negative for DVT. Musculoskeletal ultrasound did not show any intra-articular effusion in the left knee. FINAL/WORKING DIAGNOSIS: IgA Vasculitis (formerly known as Henoch-Schnolein Purpura) with polyarticular involvement. TREATMENT AND OUTCOMES: Our patient was managed conservatively with symptom management as needed. Although there was concern for septic arthropathy, she remained afebrile with no clinical signs of sepsis. The rash and arthralgias resolved within 4 weeks.

Clinical and virological responses to a broad-spectrum human monoclonal antibody in an influenza virus challenge study

Influenza A infections cause significant seasonal morbidity and mortality as well as periodic pandemic infections. Currently, no approved therapies exist for patients hospitalized with influenza. The efficacy of VIS410, a broadly neutralizing human immunoglobulin IgG1 monoclonal antibody engineered to bind to the stem region of group 1 and 2 influenza A hemagglutinins, was explored in experimental human influenza infection. Healthy volunteers were inoculated with influenza A/California/07/2009 (H1N1) and received a single dose of VIS410 or placebo 24 h later. Subjects were monitored for symptoms, viral shedding, and safety, including cytokine measurements. The primary efficacy endpoint was the area under the curve (AUC) of viral load (VL) in the VIS410 group versus placebo. VIS410 treatment was associated with a 76% reduction in median VL AUC as measured by qRT-PCR (p = 0.024). Similar VIS410 antiviral activity was observed by virus culture, with a 91% reduction in median VL AUC by TCID50 (p = 0.019) compared to placebo-treated volunteers. Influenza symptoms were generally mild or moderate, with a trend toward faster resolution in VIS410-treated subjects. Treatment with VIS410 was generally safe, with an increase in gastrointestinal events that were largely mitigated by pre-treatment with oral diphenhydramine (50 mg) in combination with 600 mg of ibuprofen. Transient elevation of specific cytokines (IL-8 and TNFα) were associated with gastrointestinal adverse events. Treatment with VIS410 did not interfere with the endogenous immune response to influenza A. These data indicate that VIS410 may provide therapeutic benefit in influenza A infection. Trial registrationClinicaTtrials.gov Identification NCT02468115; https://clinicaltrials.gov/ct2/show/NCT02468115?term=NCT02468115&rank=1).

Effect of diphenhydramine and cetirizine on immediate and late-phase cutaneous allergic reactions in healthy dogs: a randomized, double-blinded crossover study.

Currently, there is insufficient evidence to confirm oral diphenhydramine (DPH) efficacy to prevent mast cell degranulation and histamine release in dogs. To determine and compare the effects oral of DPH and cetirizine on the immediate- and late-phase cutaneous allergic reactions in healthy dogs. Twelve healthy laboratory beagle dogs. The study was designed as a randomized, double-blinded crossover study in which each dog served as its own control; twice-daily oral DPH (2.2mg/kg) or cetirizine (2mg/kg) were given for six days with a two week washout period. Intradermal injections of histamine, compound 48/80 (positive control) and saline (negative control) were performed on the right thorax 10days before drug administration (baseline), during oral antihistamine administration on Day 6 and 10days after last medication dosage. Global wheal scores (GWS) at 20min and late-phase reactions (LPR) at 6h post-injection were evaluated by an investigator blinded to the drug and the interventions. Treatment with cetirizine significantly reduced histamine and compound 48/80 GWS and LPR compared to baseline; there was no significant difference for DPH. In all dogs, oral DPH and cetirizine reached plasma concentrations considered therapeutic in people. No adverse effect or behavioural changes were observed during the study. In conclusion, oral cetirizine was effective in preventing cutaneous allergic reactions without any obvious adverse effects in dogs. Oral DPH failed to show an inhibitory effect despite attaining plasma drug concentrations that are considered effective in people.

A retrospective cost analysis of the frequency and cost of transfusion premedications.

Acetaminophen and diphenhydramine are routinely administered to prevent febrile non-hemolytic and allergic blood transfusion reactions despite multiple randomized controlled trials demonstrating that this practice lacks efficacy. As a result, patients are exposed to the adverse effects of these medications and their financial burdens with no expected benefit. The aim of this study was to quantify the frequency and cost of transfusion premedications in patients with acute myeloid leukemia (AML). This was a retrospective study of patients with AML admitted to Vanderbilt University Medical Center (VUMC) for induction chemotherapy between January 2008 and December 2016. Data were collected on the number of platelet and packed red blood cell (PRBC) transfusions each patient received during the initial inpatient encounter for AML, as well as on the administration of premedications prior to each transfusion. During the 9-year study period, 948 AML patients received a total of 19,820 transfusions. Of these, 30% were preceded by oral diphenhydramine, 8% by intravenous diphenhydramine, and 39% by oral acetaminophen. The percentage of patients that received a transfusion preceded by a premedication increased over the study period (p = 0.03), as did the percentage of transfusions preceded by a premedication (p = 0.02). The total unadjusted cost of pre-transfusion medications to the institution during the study period was $50,309.77, or $52.67 per patient with AML. The cost of premedications per patient did not increase over the study period (p = .45). Routine transfusion premedication administration is common in AML patients and not well-supported by available evidence.

Evaluation of Intravenous Diphenhydramine Use in Patients with Sickle Cell Vaso-Occlusive Crisis

Inpatient management of sickle cell disease (SCD) vaso-occlusive crisis (VOC) often involves use of high-dose opioids, which may result in opioid-induced pruritus (OIP). This OIP is typically treated with antihistamines like diphenhydramine either orally or intravenously. The oversedation adverse effects of diphenhydramine may be magnified when given in combination with high-dose opioid therapy. Current recommendations made by the National Heart, Lung, and Blood Institute endorse using oral rather than intravenous (IV) antihistamines to avoid the cumulative effect on sedation. Despite this guideline, IV diphenhydramine use is still prevalent in many hospitals that treat persons with SCD. We performed a retrospective, single-center, cohort study comparing rates of oversedation among patients who received IV and oral diphenhydramine for management of opioid-induced pruritus in a large SCD inpatient population. Patients with SCD VOC admitted to an urban hospital between June 1, 2016 to July 30, 2017 were included if they were ≥ 18 years old and received either IV or oral diphenhydramine for OIP. Exclusion criteria: Pregnancy, received <24 hours of diphenhydramine, or <50% of their “as needed” doses of diphenhydramine. Primary endpoint: comparative incidence of oversedation in SCD VOC receiving IV versus oral diphenhydramine. Oversedation was defined as meeting two or more of the following criteria: documentation of oversedation in clinician notes, medication doses held by a nurse due to sedation, a PASERO opioid-sedation score ≤3, or documented hypoxemia with O2 percent saturation ≥ 2 points below baseline. Secondary endpoints included: evaluation of hospital length of stay, amount of diphenhydramine administered per day, indication for IV therapy, and number of days receiving diphenhydramine. Individual admissions were portioned by route of diphenhydramine administration cohorts (IV versus oral). Within each cohort, study endpoints were derived at the patient level. Oversedation was determined at the patient level i.e. experiencing at least one occurrence over the course of their admissions. The number of admissions, length of stay, and days of diphenhydramine treatment were totaled across admissions for each patient. The daily dose of diphenhydramine administration (mg/day) was averaged across the admissions per patient. The proportion of subjects experiencing oversedation was summarized by cohort and compared using Fisher's exact test. Length of stay, number of days on treatment, and average daily dose of diphenhydramine were analyzed with analysis of variance (ANOVA) techniques. Length of stay and number of days on treatment were log-transformed prior to statistical analyses. The number of admissions was analyzed with Poisson regression. Fifty unique patients were included in the analysis representing 121 admissions. Seven patients received both formulations on separate admissions and were included in both groups, 15 received oral diphenhydramine, and 42 received the IV formulation. The percent of patients experiencing oversedation was higher in the IV group, however the difference was not statistically significant (p = 0.312). The average number of admissions was significantly higher in the IV versus oral group (2.45 vs. 1.20; p = 0.005) with average and median length of stay also significantly higher in the IV versus oral group (30.57, 16.0 vs. 10.67, 10.0; p = 0.003). Similarly, the average and median number of days on diphenhydramine treatment in the IV group was significantly higher than in the oral group (28.79, 14.5 vs. 9.73, 7.0; p = 0.001). The average daily dose of diphenhydramine was similar in the two cohorts with no compelling indications documented for use of IV over oral formulation. In summary, while we did not find a statistically significant difference in the rates of oversedation with use of IV versus oral diphenhydramine formulations, patients with SCD VOC who received IV diphenhydramine were more likely to have more frequent admissions, and a longer length of stay. These findings have clear impact on clinical outcomes and cost of care and clinicians may consider oral diphenhydramine preferentially in appropriate patients over IV administration. Larger, prospective studies are needed to evaluate the absolute risk to benefit ratio between the two formulations particularly among person receiving concomitant parenteral opioid therapy. DisclosuresOsunkwo:Terumo BCT: Speakers Bureau; Prolog Pharmaceuticals LLC: Consultancy; Novartis Pharmaceuticals LLC: Consultancy, Speakers Bureau. Symanowski:Immatics: Other: Data Safety Monitoring Board; Eli Lily & Co: Other: Data Safety Monitoring Board; Boston Biomedical: Other: Data Safety Monitoring Board ; Five Prime Therapeutics: Other: Data Safety Monitoring Board .

SLEEPING WITH THE DEVIL: PREVENTING DIPHENHYDRAMINE USE FOR INPATIENT INSOMNIA

SESSION TITLE: Education, Research, and Quality Improvement 2 SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/10/2018 01:00 pm - 02:00 pm PURPOSE: To design and implement an educational intervention to decrease the misuse of oral diphenhydramine for the treatment of insomnia. METHODS: A retrospective review was first conducted examining all one time and PRN orders for diphenhydramine placed during the hours of 8:00PM to 7:00AM, for any patients admitted to our general medical floor service. Data was collected for four consecutive months (March-June) in 2015. We analyzed the baseline frequency of prescription as well as the level of training of the most frequent prescribers to help determine our target group for the intervention. Concurrently, we created an educational presentation that focused on the treatment of inpatient insomnia based on the AAFP guidelines, as well as a brief explanation of contraindications and side effects for diphenhydramine use. During the same four month period of the following year (March – June of 2016), we gave our educational presentation to each of the incoming night shift post-graduate year one (PGY-1) residents. We then examined all one time and PRN diphenhydramine orders placed during the intervention period, during the hours of 8:00PM to 7:00AM. RESULTS: From March to June of 2015, there were 110 one-time or PRN orders for diphenhydramine. 22 of the orders listed insomnia as the indication, and 88 orders had no indication listed. 88 of the orders were one-time orders, and 22 of them were PRN. 87% of these orders were placed by PGY-1 residents. Prescription frequency varied between months by 7 (26 to 33). During the intervention period, there were 16 one-time or PRN orders for diphenhydramine marking an 85% reduction in comparison to the prior year. Of the 16 orders, 15 were one-time orders and 1 was PRN. 2 of had insomnia listed as the indication, while 14 of them had no indication. There was a 90% reduction regarding the former. The total prescription frequency varied by 5 between months (2 to 7). Majority of the orders during the intervention period were placed by the PGY-1 residents (82%). CONCLUSIONS: The implementation of a targeted educational intervention is successful in preventing the use of diphenhydramine to treat insomnia in the inpatient general medical floor setting. CLINICAL IMPLICATIONS: With our educational intervention, we observed a dramatic decrease of the use of diphenhydramine overnight. However, there are several limitations to the study in its ability to claim prevention of diphenhydramine misuse. The largest one is that our data did not allow us to distinguish the clinical reason for each individual diphenhydramine order. A majority of the orders did not have any indications listed, and its use may have been warranted in that particular scenario. We attempted to overcome this by comparing the total number of overnight diphenhydramine prescriptions, as well as those with insomnia listed as an indication, as a surrogate marker for the outcome. DISCLOSURES: No relevant relationships by Oki Ishikawa, source=Web Response No relevant relationships by Dmitry Kozhevnikov, source=Web Response

Intravenous Corticosteroid Premedication Administered 5 Hours before Computed Tomography Compared with a Traditional 13-Hour Oral Regimen: Mervak BM, Cohan RH, Ellis JH, et al. Radiology. 2017;285(2):425-433

In patients at risk of an adverse allergic-like reaction to intravenous (IV) contrast media The American College of Radiology recommends pretreatment with corticosteroids and antihistamines. The most common regimen is a 13-hour course consisting of oral steroids and diphenhydramine administered at set times before administration of IV contrast. There is minimal data to support the use of an accelerated protocol for pretreatment before IV contrast. The goal of this study was to show that a 5-hour accelerated pretreatment regimen was noninferior to the commonly used 13-hour regimen. The study design was based on a single center retrospective cohort analysis. The authors’ institution already had implemented a 5-hour accelerated pretreatment protocol. By electronically searching both for notes signed in the Electronic Medical Record (EMR) and orders placed in the EMR, 202 subjects were identified that had previously undergone a 5-hour pretreatment protocol for prevention of prior documented allergic-like or unknown reactions to IV contrast between June 2008 and June 2016. The 5-hour protocol consisted of 200 mg IV hydrocortisone at hours 5 and 1 prior to computed tomography (CT) and 50 mg IV diphenhydramine at 1 hour prior to CT. The other study arm consisted of 626 subjects that underwent the 13-hour pretreatment protocol. The data was derived from a previous study published by the same authors in 2015. The protocol consisted of 50 mg oral prednisone administered at hours 13, 7, and 1 prior to CT with IV contrast and 50 mg oral diphenhydramine administered at 1 hour prior to CT with IV contrast. The breakthrough reaction rate for the 5-hour cohort was 2.5% (5/202 patients; 95% confidence interval (CI) 0.8-5.7%). This was found to be noninferior to the 13-hour cohort breakthrough allergic reaction rate of 2.1% (13/626 patients; 95% CI 1.1-3.5%). The upper limit of the 95% confidence interval for the difference between the two rates was 3.7%. This fell below the 4% margin that the authors predetermined would satisfy noninferiority between the cohorts. None of the 5 subjects that experienced breakthrough reactions died and only 1 was treated with epinephrine. The two study arms shared similar demographics in regards to sex, age, and rates of prior moderate and severe allergic-like reactions to IV contrast. The main differences between the groups were that significantly more subjects in the 5-hour IV regimen had a prior mild allergic-like reaction to IV contrast (51% vs 34%, p<.0001) and significantly more subjects in the 13-hour oral regimen had a prior unknown type reaction to IV contrast (38% vs 15%, p<.0001). The authors concluded that a 5-hour accelerated pretreatment protocol using IV medications was noninferior to a 13-hour protocol using oral medications in preventing allergic reaction to IV contrast prior to CT scan. They recommend institutions adopt the 5-hour protocol in emergency departments and inpatient settings. Comment: Despite its retrospective cohort design, this study provides the best evidence to date that a 5-hour pretreatment is as good in preventing allergic-like reactions to IV contrast. If a 5-hour protocol were adopted for emergency department patients, it would likely expedite time to diagnoses, reduce length of stay and improve throughput without increasing risk to the patients.

P378 A case of the nerves tiotropium for treatment of resistant anaphylaxis with vocal cord dysfunction

A 17-year-old girl with an allergy to house dust mites presented with recurrent and frequent episodes (2-3 per week) of acute lip/tongue angioedema, diffuse rash, and respiratory distress with inspiratory stridor. Most episodes were triggered by exposures to scents from perfumes and soaps. Despite prophylactic treatment with inhaled and nasal fluticasone propionate and an oral regimen of daily diphenhydramine, cetirizine, and hydroxyzine, as well as on demand intramuscular epinephrine and multiple courses of oral steroids, she experienced over fifteen episodes requiring emergency room visits and four hospital admissions. She was diagnosed with Vocal Cord Dysfunction (VCD) as an outpatient by speech pathology using nasal laryngoscopy and was taught breathing and relaxation exercises. Her symptoms persisted and she was started on inhaled tiotropium at 5mcg daily. Since receiving tiotropium and maintenance H1 blockers, she had only one episode of anaphylaxis without respiratory symptoms, resolving with self-administration of oral diphenhydramine and intramuscular epinephrine.

Effects of oral premedication on cognitive status of elderly patients undergoing cardiac catheterization.

BackgroundSedatives and analgesics are often administered to achieve conscious sedation for diagnostic and therapeutic procedures. Appropriate concerns have been raised regarding post procedure delirium related to peri-procedural medication in the elderly. The objective of this study was to investigate the effect of premedication on new onset delirium and procedural care in elderly patients.MethodsPatients ≥ 70 years old and scheduled for elective cardiac catheterization were randomly assigned to receive either oral diphenhydramine and diazepam (25 mg/5 mg) or no premedication. All patients underwent a mini mental state exam and delirium assessment using confusion assessment method prior to the procedure and repeated at 4 h after the procedure and prior to discharge. Patients' cooperation during the procedure and ease of post-procedure were measured using Visual Analog Scale (VAS). The degree of alertness was assessed immediately on arrival to the floor, and twice hourly afterwards using Observer's Assessment of Alertness/Sedation Scale (OAA/S).ResultsA total of 93 patients were enrolled. The mean age was 77 years, and 47 patients received premedication prior to the procedure. None of the patients in either group developed delirium. Patients' cooperation and the ease of procedure was greater and pain medication requirement less both during and after the procedure in the pre-medicated group (P < 0.05 for both). Nurses reported an improvement with patient management in the pre-medicated group (P = 0.08).ConclusionsIn conclusion, premedication did not cause delirium in elderly patients undergoing cardiac catheterization. The reduced pain medication requirement, perceived procedural ease and post procedure management favors premedication in elderly patients undergoing cardiac catheterization.

Effectiveness of oral ketamine, midazolam, and atropine cocktail versus oral diphenhydramine for pediatric sedation in the emergency department.

Background:Sedation is a condition of reduced level of consciousness (LOC) for a patient that is created to decrease irritability, anxiety, and restlessness.Objectives:In this study, we compared the sedative effect of oral administration of ketamine, midazolam, and atropine cocktail with diphenhydramine in the referent children to the emergency department.Patients and Methods:Based on the double-blind randomized clinical trial in this investigation, 80 children, who needed to repair their wounds with suture were randomly divided into two groups: group 1 and group 2, who have received oral diphenhydramine and oral ketamine, midazolam, and atropine cocktail, respectively. Behavioral changes were collected and recorded before, during intervention and two weeks after intervention. Statistical data were analyzed by SPSS-16 software and chi-square and Mann-Whitney U tests were employed to study the relations among variables. P < 0.05 was considered statistically significant.Results:There was no significant difference between two groups in terms of drug acceptance and anxiety degree in children before intervention. Group 2 had achieved better and deeper sedation than group 1 during 45-minute post-medication (P < 0.05, P = 0.01). Regarding pediatric general behavior such as crying or interruptive moves, there was also a significant statistical difference between group 2 and group 1 (P = 0.009) based on Houpt Classification. The mean recovery times in groups 1 and 2 were 34.37 ± 14.23 min and 27.25 ± 5.14 min, respectively (P = 0.003). In terms of behavioral changes, the rate of cumulative frequency was computed for behavioral changes two weeks after the discharge from emergency department in which there were less behavioral changes in group 2 than in group 1 (P = 0.04).Conclusions:Oral administration of ketamine, midazolam, and atropine cocktail induces better sedation than diphenhydramine with respect to its limited mood changes in children, who need a medical procedure at emergency department.