Administration Of Diphenhydramine Research Articles

Intraoperative Administration of Diphenhydramine Attenuates Postoperative Catheter Related Bladder Discomfort in Patient Following Percutaneous Nephrolithotomy

Background: We intend to evaluate the effect of intraoperative diphenhydramine administration on incidence and severity of catheter related bladder discomfort (CRBD) and pain after percutaneous nephrolithotomy. Methods: In a double blind randomized clinical trial, adult male patients undergoing percutaneous nephrolithotomy were enrolled. They were randomized into two groups by a computerized digital random allocation method. Before anesthesia induction, group D (Diphenhydramine group) (n = 48) received 5 ml normal saline containing 0.5 mg/kg of diphenhydramine intravenously. In group C (Control group) (n = 48), 5 ml of normal saline was injected in the same manner. Induction and maintenance of anesthesia were identical in both groups. The incidence and severity of CRBD and postoperative pain were assessed at recovery room. Results: The incidence of CRBD was significantly lower in group D than in group C (14% vs. 63%, P=0.001). The severity of CRBD was milder in group D in comparison to group C (P<0.05). Postoperative pain score was significantly lower in group D (P<0.05). Conclusion: Intraoperative administration of diphenhydramine is an effective practice for the prevention of CRBD after percutaneous nephrolithotomy in male patients and can reduce postoperative pain as well.

Evaluation of outpatient prescription patterns of COVID-19 drugs in Iran: comparison of real practice with local therapeutic recommendations

BackgroundA comprehensive guideline named “Diagnostic Therapeutic Flow Chart for Covid-19″ (DTFC) was released by the Scientific Committee of Covid-19 of Iran’s Ministry of Health and Medical Education and regularly was updated. The aim of this study was to compare the prescription pattern of drug treatment in outpatient Covid-19 patients with the DTFC.MethodsA cross-sectional study was conducted on the prescription pattern of drugs given to outpatients with a diagnosis of Covid-19, in Isfahan City from June to September 2021 (concurrent with the fifth peak of Covid-19 in Iran) taking into account the recommendations of the 9th version of DTFC (December 2020). A total of 8250 prescriptions were retrieved from the Public Health Department of Isfahan City.ResultsFamotidine 20, 40 mg tablets (N = 936 patients) was the most prescribed drug followed by dexamethasone ampule (N = 588), prednisolone 5, 50 mg tablets (N = 478), azithromycin 250, 500 mg capsules (N = 452), diphenhydramine syrup (N = 362), vitamin D3 soft gel 50,000 Iu (N = 526), naproxen 250, 500 mg tablets (N = 266) and favipiravir 200 mg tablet (N = 191). The following drugs were administered against the recommendation of the DTFC-9: azithromycin, favipiravir, remdesivir, cetirizine, corticosteroids, vitamin C, vitamin B12, multivitamins, proton pump inhibitors (e.g., omperazole, anticoagulants (rivaroxaban,….), aspirin and ivermectin. Administration of analgesics, famotidine, hydroxychloroquine, vitamin D3, diphenhydramine and statins were in concordance with the DTFC-9.ConclusionIn this study, we showed frequent use of drugs with unproven efficacy in outpatient cases of Covid-19 mostly attributed to corticosteroids and antibiotics use. Our research highlights the discrepancy between recommendations for care and clinical practice and the need for strategy to bridge gaps in evidence-based informed decision-making.

Retrospective Review of Patients Treated with Intrathecal Rituximab for Primary and Secondary CNS Lymphoma and Leukemia

Background: Rituximab has been studied and incorporated into the treatment of primary and secondary CNS lymphoma (Grommes 2017; Bobillo 2023). Systemic rituximab, a CD20-targeting monoclonal antibody, is widely used in the treatment of various B-cell malignancies (Klein 2021); however penetration into the central nervous system (CNS) is limited (Petereit 2009; Harjunpää 2001). Although there are conflicting data regarding the efficacy of IV rituximab in primary CNS lymphoma (Schmitt 2019; Ferrari 2022; Bromberg 2019), its role in other B-cell malignancies with CNS involvement has not been adequately described. In particular, its role in treating the cerebrospinal fluid (CSF) space is unclear. The rationale for direct administration of rituximab into the CSF via lumbar puncture or Ommaya reservoir is to allow for consistent treatment of this compartment in order to effectively clear the CSF of lymphoma cells (Kadoch 2014). Limited data exist regarding the efficacy and safety of intrathecal rituximab (Bonney 2011 Aslan 2022; van de Fling 2008; Santiago 2021; Soares 2019). Current intrathecal armamentarium for leptomeningeal lymphoma is very limited and more data on the efficacy and safety of intrathecal rituximab is needed in these patients. Methods: This is a retrospective, single center study of adult patients with a diagnosis of leukemia or lymphoma who received intrathecal (IT) rituximab between 1/1/2016 and 12/31/2022 at Hackensack Meridian Health. Rituximab 25 mg IT was administered weekly either via lumbar puncture or into an Ommaya reservoir. The primary objective of this study was to evaluate the efficacy and safety of IT rituximab. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan Meier method. Descriptive statistics were used to summarize data for categorical and continuous variables. Results: Twelve patients were identified to have received IT rituximab at our institution between 1/1/2016 and 12/31/2022. Median age was 60 years (range 45-81), 54% were male, and 69% white. Disease types included primary CNS lymphoma (67%), diffuse large B-cell lymphoma (17%), PTLD of the CNS (8%), and chronic lymphocytic leukemia (8%). In regards to CNS disease involvement, 58% of patients presented with parenchymal and leptomeningeal disease, 33% with leptomeningeal disease only, and 8% with parenchymal disease only. There were 12 patients who received IT rituximab for the treatment of malignant CNS disease with characteristics and outcomes as shown in Table 1. The median number of IT rituximab treatments administered were 8 (range 2-9). Of the 10 patients evaluable for response, 92% of patients achieved complete response in the CSF following treatment with IT rituximab as evaluated by flow cytometry, cytology, cell count and protein levels in CSF. One patient that did not achieve CSF remission has an unusual case of relapsing/remitting CLL and leukemic meningitis. There were 2 patients unevaluable for response to IT rituximab: one patient received only 2 treatments prior to switching to hospice care; and the other patient had a severe adverse reaction (tightening of throat, flushing, toe numbness) after IT rituximab and was not continued on treatment. At a median follow-up of 19.7 months, median PFS was not reached (NR) (95% CI, 0.5-NR) ( Figure 1). Median OS was 70.1 months (95% CI, 1.2-NR). Six (50%) patients experienced adverse reactions from IT rituximab treatment, including perioral numbness, headache, nausea, and flushing ( Table 1). No treatment-related deaths occurred. One (8%) patient experienced a severe adverse reaction following administration of IT rituximab. This patient developed tightening of the throat, flushing, and toe numbness after the first IT rituximab and symptoms resolved with administration of hydrocortisone and diphenhydramine. No further IT rituximab doses were administered. Another patient experienced a mild reaction consisting of headache, fatigue, nausea, diaphoresis, hypotension, and bradycardia following the fourth dose of IT rituximab in combination with IV rituximab, but was able to complete his treatment course. Conclusions: The use of IT rituximab appears safe and showed promising activity in B cell malignancies, specifically as part of induction in patients with leptomeningeal disease and PCNSL as those patients achieved cytologic response.

B-337 Case Report: Fatal Opioid Overdose Induced by Over-the-Counter Cold Medication Diphenhydramine

Abstract Background Accidental drug-related deaths frequently arise following ingestion of multiple co-intoxicants, including opioid analgesics. Hydrocodone, the most prescribed opioid for pain management, is metabolized by hepatic enzymes CYP2D6 and CYP3A4 to the pharmacologically active metabolite hydromorphone and the inactive metabolite norhydrocodone, respectively. As a result, inhibition of CYP2D6 by other pharmacologic agents can impair the analgesic properties of hydrocodone and prolong its half-life in circulation. One such example is diphenhydramine, which is a potent inhibitor of CYP2D6 activity. This case highlights a drug-drug interaction likely resulting in an accidental fatal opioid overdose. Case Presentation A 58-year-old female had longstanding prescriptions for hydrocodone/acetaminophen (Norco® 10/325), alprazolam, carisoprodol, and diltiazem. The decedent had recently taken an over-the-counter cold medication, diphenhydramine (Benadryl), shortly preceding death. A toxicology report (NMS labs, Horsham, PA) from a post-mortem femoral blood sample detected the presence of the following therapeutic compounds by High Performance Liquid Chromatography/Time of Flight-Mass Spectrometry (LC/TOF-MS) analysis: acetaminophen (14 μg/mL), hydrocodone (410 ng/mL), dihydrocodeine (hydrocodol, 24 ng/mL), alprazolam (42 ng/mL), carisoprodol (88 ng/mL), diltiazem (110 ng/mL), and diphenhydramine (150 ng/mL). Hydromorphone, the active metabolite of hydrocodone, was not detected (<2 ng/mL). With the exception of hydrocodone, which was present at fatal concentrations, all other compounds were within therapeutic range. Together, these observations are strongly suggestive of a drug-drug interaction leading to impaired hydrocodone metabolism. Conclusions This case report highlights a fatal opioid overdose as a result of CYP2D6 inhibition by diphenhydramine, a readily available over-the-counter medication. Post-mortem toxicological analysis revealed hydrocodone was present in lethal concentrations, whereas its pharmacologically active metabolite, hydromorphone, was undetectable at time of autopsy. Further, the patient was prescribed a formulation of hydrocodone in combination with acetaminophen, which was present at therapeutic concentrations despite the two drugs having similar elimination half-lives. These toxicological findings suggest administration of diphenhydramine precipitated a deadly accumulation of hydrocodone in the deceased. Overall, this case report underscores the importance of understanding and preventing harmful drug-drug interactions in patients taking opioid medications for pain management.

Comparative Analysis of Rapid vs Standard Premedication Protocols for Contrast Allergy

Contrast reaction rates have been poorly studied with nonionic low osmolar agents. Premedication protocols to prevent contrast reactions to ionic high osmolar contrast have been studied in the past; however, protocol outcomes for the currently used nonionic low osmolar contrast is less clear. The purpose of this study was to evaluate the rate of contrast reactions with nonionic low osmolar using the standard premedication protocol as well as the effect of using a rapid premedication protocol. Retrospective single institution review of computed tomography (CT) scans from May 2011 through January 2022 was performed by searching the Cerner Soarian medical records system for patients with documented contrast allergies who received contrasted CT scans. The patients were then divided into groups depending on whether they received the 13-hour premedication protocol vs the 4-hour rapid protocol. Contrast reaction was extrapolated from administration of prednisone, hydrocortisone, diphenhydramine, or epinephrine outside of protocol within one hour with corresponding indication in the ordering system. Basic statistical analysis including χ2 testing was performed on acquired data. We performed 2588 premedicated contrasted CT cans during the study period, 2102 (81.2%) of which underwent the 13-hour premedication protocol and 486 (18.7%) underwent 4-hour premedication protocol. The average age of the 13-hour group was 62 years (range, 11-92) years and 1345 (64%) were female and the 4-hour protocol had an average age of 61 years (range, 5-92 years) and 277 (57%) were female. In the 13-hour group, there was an overall contrast reaction rate of 29% (613): 124 patients received prednisone, 107 hydrocortisone, 388 diphenhydramine, and 3 epinephrine. In the 4-hour group, 44% (214) patients had a contrast reaction: 78 received prednisone, 89 hydrocortisone, 41 diphenhydramine, and 6 epinephrine. There was significantly more treatment for contrast reaction in the 4-hour protocol group (P < .01). Protocols for premedication to prevent contrast allergy reactions have been based on ionic high osmolar contrast usage and have not been separately validated for use with nonionic low osmolar contrast agents. This study demonstrates that the preexisting protocols appear only partially effective in preventing contrast reactions and the outcomes for the rapid 4-hour protocol performed significantly worse than the standard protocol. These outcomes show the need for further study and protocol refinement as well as continued vigilance for contrast reactions while using the current protocols.

Reducing paclitaxel hypersensitivity reactions in gynecologic oncology patients (521)

Reducing paclitaxel hypersensitivity reactions in gynecologic oncology patients (521)

Analysis of Adverse Events and Intravenous Iron Infusion Formulations in Adults With and Without Prior Infusion Reactions

Although iron deficiency is common, it remains unclear which iron repletion strategy is associated with the lowest rate of infusion-related adverse events, and how patients with history of infusion reaction should be managed. To evaluate rates of infusion reactions among 4 commonly used intravenous iron repletion strategies and determine how readministration was managed in patients with history of reaction. This cohort study included all patients receiving intravenous iron infusion from January 1, 2015, to September 7, 2021, at 6 centers in Portland, Oregon. Participants included a total of 12 237 patients with iron deficiency, not restricted by etiology. Statistical analysis was performed from September to October 2021. Type of intravenous iron formulation and concurrent administration of diphenhydramine, epinephrine, famotidine, and/or hydrocortisone, used as surrogate maker of infusion reaction. Incidence of adverse events, including severe events requiring epinephrine, stratified by type of iron formulation, and in patients who received premedication or with history of infusion-related reaction receiving subsequent doses. Among 35 737 unique iron infusions (12 237 patients [9480 (77.5%) women; 717 (5.9%) Black; 10 250 (83.7%) White; mean (SD) age of 51 (20) years]), comprising 22 309 iron sucrose doses, 9067 iron dextran total doses (1771 preceded by test dose, 56 test doses alone), 3147 ferumoxytol doses, and 1214 ferric carboxymaltose doses, incidence of adverse events was 3.9% (n = 1389; 95% CI, 3.7%-4.1%). Rate of infusion events differed among iron formulations: 4.3% (n = 970; 95% CI, 4.1%-4.6%) iron sucrose, 3.8% (n = 345, 95% CI: 3.4%-4.2%) iron dextran (test and full doses or test dose alone), 1.8% (n = 57; 95% CI, 1.4%-2.3%) ferumoxytol, and 1.4% (n = 17, 95% CI, 0.8%-2.3%) ferric carboxymaltose (P < .001). Severe adverse events were exceedingly rare with only 2 documented epinephrine administrations, both associated with iron dextran. Incidence of adverse events among those who received premedication was 23-fold higher compared with those who did not (38.6% vs 1.7%, χ21 = 7324.8; P < .001). Among 873 patients with history of infusion reaction who underwent readministration, the majority received the same formulation, which was associated with significantly higher reaction rate particularly if premedication was administered (68% [95% CI, 64%-72%] vs 32% [95% CI, 26%-41%], respectively), compared with those who received an alternate formulation (21% [95% CI, 11%-35%] vs 5% [95% CI, 2%-12%], respectively) (P < .001). These data, and the preponderance of published evidence, suggest that intravenous iron is generally well tolerated with exceedingly low risk of severe reaction, use of premedication and test doses are unnecessary, and that optimal prevention and management of infusion-related reactions warrant further study.

28137 Pediatric pemphigus foliaceus and rituximab treatment

Pemphigus foliaceus (PF) is a rare blistering disease characterized by fragile vesicles and bullae in a seborrheic distribution that progress to well demarcated, scaly crusted erosions in the absence of mucosal involvement. In the pediatric population, the morphology of PF may appear polycyclic or arcuate. In cases of PF refractory to multiple therapies, rituximab infusion has been reported as inducing remission. Rituximab infusion is known to cause an infusion reaction in some first time recipients of the medication, related to rapid cytokine release. We report a case of a 7-year-old female (Fitzpatrick skin type VI) with a 19-month history of biopsy-proven PF involving her scalp, face, chest, back, arms, and legs. Her disease was refractory to prednisone, mycophenolate mofetil, and topical therapy. Infusion of rituximab 500 mg (375 mg/m2 * 1.45 m2) was administered, with acetaminophen and diphenhydramine for premedication. The patient did not receive the full intended dose, secondary to an infusion reaction marked by chest pain, fever, tachypnea, and tachycardia. This reaction resolved with discontinuation of rituximab infusion and administration of diphenhydramine. Despite this adverse event, rituximab resulted in near complete resolution of disease on previously affected areas. At nearly 1 year follow-up, the patient has only mild scalp involvement without other bodily involvement, while on daily mycophenolate mofetil and topical therapy. To our knowledge, this case is one of few in the literature detailing an adverse event related to rituximab infusion for PF that necessitated discontinuation of infusion but led to significant improvement in disease.

Prophylactic administration of diphenhydramine/paracetamol reduced emergence agitation and postoperative pain following maxillofacial surgeries: a randomized controlled trial.

Emergence agitation after maxillofacial surgeries is an anxious and problematic complication for the surgeon and anesthesiologist that may lead to self-extubation, haemorrhage, and surgical destruction. In this study, we investigated the effects of preemptive administration of diphenhydramine on emergence agitation and quality of recovery after maxillofacial surgery in adult patients. Eighty-five patients undergoing maxillofacial surgery were randomized into two groups. The diphenhydramine group (Group D, n = 40) received diphenhydramine premedication 0.5mg/kg before anesthesia induction, while the control group (Group C, n = 40) received volume-matched normal saline as a placebo. Before incision, all patients receive 0.1mg/kg morphine sulfate slowly intravenously within 5min. Continuous infusion of remifentanil 0.2μg/kg/h and inhalation of isoflurane was maintained during the anesthesia period. Paracetamol 1g was infused 15min before extubation. We evaluated the incidence of agitation during the extubation period after general anesthesia, hemodynamic parameters, and recovery characteristics during the postoperative period. During extubation time, the incidence of emergence agitation was lower in Group D than in Group C (16% vs. 49%, P = 0.041). The time from isoflurane discontinuation to extubation (7.7min in Group D vs. 6.8min in Group C, P = 0.082) was not different. Grade of cough during emergence, the severity of pain, analgesic requirements, and hemodynamic changes were lower in group D compared with Group C. Preemptive administration of diphenhydramine provided smooth emergence from anesthesia. It also improved the quality of recovery after maxillofacial surgery. This study was registered at http://irct.ir (registration number IRCT20130304012695N3).

Effect of the Dexamethasone and the Difenihidramiana on the Degranulation of the Eosinophilic Granular Cell of Tilapia

The aim of this study was to determine the relationship between EGC degranulation in fish injected with formalin-killed Escherichia coli and the effect of dexamethasone, diphenhydramine supplied separately and before formalin-killed E. coli. We performed a quantitative analysis of the number of cell granules and demonstrated that: compared to the EGCs of animals, the injection of dead E. coli with formalin generated degranulation of the EGC, while the administration of dexamethasone alone did not show significant differences with control group animals. The administration of diphenhydramine alone did not show significant differences neither with the animals of the dexamethasone treated group nor with those of the control group. When dexamethasone was administered one hour before the E. coli injection, degranulation was apparently inhibited and the number of granules did not show significant differences either with the animals in the control group or with those treated with dexamethasone. Finally, when this group was compared with the group of animals that were only injected with E. coli, the differences were statistically significant. However, when diphenhydramine was administered one hour before E. coli injection, a critical inhibition of EGC degranulation was evidenced, with a marked increase in the number of granules. All this seems to show that dexamethasone can partially inhibit the release of substances that participate in the inflammatory process. Diphenhydramine, a recognized antihistamine, inhibited degranulation of EGCs. These results suggest that EGC can release histamine like mammalian mast cells.

Prophylactic Administration of Diphenhydramine to Reduce Neuroleptic Side Effects in the Acute Care Setting: A Systematic Review and Meta-Analysis.

Neuroleptics are commonly prescribed drugs to treat acute conditions (e.g., migraines) in the emergency department, but can cause serious adverse effects. Using diphenhydramine to prevent these adverse effects is very common but remains controversial. We performed a systematic review to determine whether prophylactic administration of diphenhydramine reduces the incidence of neuroleptic adverse effects in patients with acute conditions. Medline, Embase, Cochrane, PsycInfo, and Web of Science were searched for randomized controlled trials evaluating any neuroleptic with diphenhydramine vs. the same neuroleptic with any inactive agent. Primary outcome was incidence of any extrapyramidal adverse effect. Secondary outcomes were akathisia, rescue medication, subjective restlessness, neuroleptic malignant syndrome, and sedation. Independent reviewers scanned identified citations, extracted data, and assessed risk of bias. Meta-analysis was performed using random effect models. Of 1566 identified citations, nine studies (n=1648 patients) met eligibility criteria. Four studies were specifically designed to compare the incidence of neuroleptic adverse effects with and without co-administration of diphenhydramine. Four studies were at high risk of bias. In primary analysis, diphenhydramine had no effect on the incidence of extrapyramidal symptoms (7 studies, n=1393, risk ratio [RR] 0.75; 95% confidence interval [CI] 0.44-1.31) or akathisia (5 studies, n=1094; RR 0.78; 95% CI 0.33-1.82) or any of the secondary outcomes. In subgroup analysis, diphenhydramine was associated with a significant decrease in extrapyramidal adverse effects compared with placebo (4 studies, n=705; RR 0.61; 95% CI 0.41-0.90). Dosage analysis yielded no further information. When compared with placebo, diphenhydramine was associated with a significant reduction of extrapyramidal adverse effects. Overall quality of evidence is low. Further studies are warranted.

Replace Red Man Syndrome With Vancomycin Flushing Reaction.

Imagine this scenario: a 14-year-old Native American boy is being treated with vancomycin for osteomyelitis caused by methicillin-resistant Staphylococcus aureus . During the first infusion, he develops diffuse flushing, which resolves with a slower infusion rate and administration of diphenhydramine. During bedside rounds the next morning, the medical student managing the patient reports that overnight the patient developed red man syndrome. An uncomfortable pause follows as the medical team recognizes the awkwardness of the phrase and as the patient and his family try to understand what message is being conveyed by “red man syndrome”: a term that would seem, erroneously, to invoke race as a key component to its pathophysiology. Providing some historical context is important. In 1959, an article entitled “An anaphylactoid reaction to vancomycin” was published in the Journal of the American Medical Association .1 The pathophysiology of this reaction was hypothesized to involve vancomycin-induced release of histamine from mast cells. Because of this and other untoward effects (eg, oto- and renal toxicity), vancomycin (a name derived from the word vanquish), was not extensively used until the proliferation of methicillin-resistant S aureus occurred in the 1970s and 80s.2 Sometime during this …

Clinical profile of acute drug-induced dystonia in children

Background: Acute dystonic reactions are the most common type of extrapyramidal reactions associated with the use of certain drugs. Drug-induced dystonic reactions (DIDRs) are diagnosed based on the detailed history and physical examination. Objective: The objective of the study was to describe the clinical profile, identify the drugs causing dystonic reactions and outcomes in a cohort of children with DIDRs. Materials and Methods: This study is a prospective observational study conducted in patients with DIDRs between February 2019 and January 2020 aged &lt;15 years. DIDRs were diagnosed on the basis of history and physical examination. Results: During the proposed study period, 12 children with DIDRs were identified with a mean age of 50.8 months and eight patients (67%) were boys. The most common cause of DIDRs was with antipsychotics in eight patients (67%) and with antiemetics in four patients (33%). All patients with DIDRs due to antiemetics were infants and received the drug with overdose. These infants needed more diagnostic investigations. Most of the children responded with stoppage of causative drug and administration of benzodiazepine and diphenhydramine. On follow-up, there was no recurrence. Conclusion: DIDRs were common with antiemetics and antipsychotics either with therapeutic dose or overdose. Benzodiazepines and diphenhydramine were more effective drugs in the treatment of DIDRs.

Cyclosomatostatin-induced catalepsy in aged rats: Specific change of brain c-Fos protein expression in the lateral entorhinal cortex

Aging represents the largest risk factor for developing Parkinson’s disease (PD); another salient feature of this disorder is a decreased brain levels of somatostatin. Recently, in aged Wistar rats, we simulated the central somatostatinergic deficiency by intracerebroventricular injections of a somatostatin antagonist, cyclosomatostatin (cSST). The treated animals displayed catalepsy, a state that resembles the extrapyramidal signs of Parkinson's disease; young animals were insensitive to cSST. The neuroanatomical substrates responsible for the increased cataleptogenic activity of cSST in aged animals, are currently unknown. To study this issue, we assessed the cSST effect on brain c-Fos-protein expression in aged and young rats; thirty three brain regions were examined. cSST was employed at the dose cataleptogenic for aged animals and non-cataleptogenic for young ones. c-Fos expression patterns in the ‘cataleptic’ and ‘non-cataleptic’ animals were very similar, with the only distinction being a decrease in the c-Fos expression in the aged lateral entorhinal cortex (LEntCx). This decrease was not observed when the cSST-induced cataleptic response was inhibited by administration of diphenhydramine and nicotine. Thus, the development of catalepsy in the aged Wistar rats appeared to be associated with a hypoactivation of the LEntCx; possibly, there exists a mechanistic link between the LEntCx hypoactivation and increased susceptibility of aged rats to catalepsy. Apparently, these findings may provide novel insight into the link between mechanisms of parkinsonian motor disorders and aging.

Use of trigger tool to identify Adverse Drugs Events in dogs.

The highlight of the shortcomings in the regulation and surveillance of veterinary drugs in Brazil is the absence of a system to report adverse drug events (ADEs). The aim of this study was evaluate the use of triggers in dogs to detect ADEs by estimating the prevalence of ADE and identifying the possible triggers. We screened medical records for ADEs and degree of harm caused by an ADE, using known triggers, with the Global Trigger Tool: translated, adapted and validated for use in animal health. The triggers comprised two-fold increase in blood urea nitrogen or serum creatinine levels compared to baseline, administration of vitamin K, administration of diphenhydramine or promethazine, excessive sedation or hypotension, administration of an antiemetic, abrupt cessation of medication, or others. The association between the occurrence of ADEs and variables, such as age, race, duration of hospitalization, polypharmacy, and clinical outcome was evaluated. A total of 148 medical records were analyzed. The trigger tools identified the known triggers 109 times in 68 medical records. Additionally, 14 ADEs were identified; the prevalence of ADEs was 9.5%. Positive predictive values of the triggers were 12.8%, and “vitamin K administration” had the best performance. The duration of hospitalization (p-value = 0.030) and polypharmacy (p-value < 0.001) were associated with the occurrence of ADEs. Approximately 46% of the hospitalized dogs presented with at least one trigger. One out of five hospitalized dogs suffered from temporary harm due to an ADE. The duration of hospitalization and polypharmacy were found to be risk factors for ADEs in dogs.

A retrospective analysis of the use of intravenous dexamethasone for postoperative nausea and vomiting in total joint replacement

BackgroundMultimodal perioperative pain-management protocols have contributed to the success of elective total joint replacement in orthopedic surgery. General or neuraxial anesthesia for arthroplasty is accompanied by complications such as pruritis, nausea, and vomiting. Dexamethasone has been demonstrated to be a safe perioperative antiemetic. This study evaluates the benefit of low-dose intravenous dexamethasone used in the perioperative period to prevent postoperative nausea and vomiting.MethodsTwo scheduled doses of 8 mg of dexamethasone 12 hours apart after total hip arthroplasty or total knee arthroplasty were given to a dexamethasone group (n = 492) and were retrospectively compared with a no-dexamethasone group (n = 364) based on the use of antiemetics in the postoperative period. Frequency of antiemetic use in both groups was compared using a zero-inflated fixed-model Poisson distribution. Additional analysis included need for opioid analgesic, administration of diphenhydramine, and postoperative infection rates at 30 and 90 days.ResultsThe dexamethasone group was found to have a significant reduction in need for the rescue antiemetic ondansetron (P = .00194). There was an associated reduction in length of stay for the treatment group (mean 1.83 days) relative to the control group (mean 2.17 days) (P < .001). There was no significant difference in postoperative infection rates at 30 or 90 days after arthroplasty.ConclusionsDexamethasone is a safe adjunct to perioperative protocol that may reduce nausea, thus improving patient satisfaction. There is an associated reduction in length of stay that may reduce cost of hospitalization.

ALEMTUZUMAB SKIN TESTING: TO DILUTE OR NOT TO DILUTE; IRRITANT OR NON-IRRITANT

Introduction Perioperative anaphylaxis is infrequent with an incidence of 1 in 2,000 – 20,000 procedures. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) used as an off-label anti-rejection therapy in renal transplantation. Case description A 60-year-old non-atopic African American male with end-stage renal disease (ESRD) secondary to nephrosclerosis developed profound hypotension (35/20 mmHg), bradycardia (35 beats per minute), ST depression on EKG, oxygen desaturation (81%), and generalized urticaria 37 minutes after induction of general anesthesia. Resuscitation was successful after administration of methylprednisolone, epinephrine, atropine, vasopressin, famotidine, and diphenhydramine. Tryptase was elevated (134.0 ng/mL; ref Discussion Perioperative hypersensitivity should include a comprehensive allergy evaluation to all agents used peri-operatively. A previous report recommended intradermal mAbs testing at dilutions of 1:100 and 1:10. Intradermal alemtuzumab has the potential to produce an irritant reaction at a 1:1000 concentration. Further studies are needed to determine nonirritant concentrations for alemtuzumab AST during allergy evaluation. Perioperative anaphylaxis is infrequent with an incidence of 1 in 2,000 – 20,000 procedures. Alemtuzumab is a humanized anti-CD52 monoclonal antibody (mAb) used as an off-label anti-rejection therapy in renal transplantation. A 60-year-old non-atopic African American male with end-stage renal disease (ESRD) secondary to nephrosclerosis developed profound hypotension (35/20 mmHg), bradycardia (35 beats per minute), ST depression on EKG, oxygen desaturation (81%), and generalized urticaria 37 minutes after induction of general anesthesia. Resuscitation was successful after administration of methylprednisolone, epinephrine, atropine, vasopressin, famotidine, and diphenhydramine. Tryptase was elevated (134.0 ng/mL; ref Perioperative hypersensitivity should include a comprehensive allergy evaluation to all agents used peri-operatively. A previous report recommended intradermal mAbs testing at dilutions of 1:100 and 1:10. Intradermal alemtuzumab has the potential to produce an irritant reaction at a 1:1000 concentration. Further studies are needed to determine nonirritant concentrations for alemtuzumab AST during allergy evaluation.

HYPERSENSITIVITY REACTION TO AMOXICILLIN-CLAVULANATE: EENY, MEENY, MINY, MOE, CATCH A REACTION BY THE SS-LACTAMASE INHIBIT…OH!

Introduction β -lactams remain the most frequently reported cause of adverse drug reactions. Isolated adverse drug reactions to Clavulanate, a β -lactamase inhibitor added to Amoxicillin to form amoxicillin-clavulanate, remain rarer. Case Description A 62-year-old male heart transplant candidate due to complicated coronary artery disease presented with a previous anaphylactic reaction secondary to amoxicillin-clavulanate for a sinus infection. Skin testing to penicillin G, penicilloate, benzylpenicilloyl polylysine and amoxicillin was negative, followed by a negative oral provocation test to amoxicillin. At a subsequent visit, the patient had negative skin testing to non-irritant concentrations of amoxicillin-clavulanate (20 mg/ml) and ampicillin-sulbactam (20 mg/ml). Clavulanate without amoxicillin was not available for testing. However, upon oral challenge with full-dose amoxicillin-clavulanate, he developed urticaria on his upper back, left upper extremity (Figure 1) and chest and experienced bilateral hand flushing that resolved over the course of two hours with the administration of IM diphenhydramine, fexofenadine and montelukast. The patient was counseled to avoid all forms of β -lactamase inhibitors and use equally efficacious alternatives. Discussion While IgE-mediated hypersensitivity reactions to penicillin are more common, IgE-mediated hypersensitivity reactions to β-lactamase inhibitors, including clavulanate, sulbactam, and tazobactam in isolation, have been reported. This case depicts an isolated β-lactamase inhibitor IgE-mediated reaction in the setting of previously negative skin testing. β -lactams remain the most frequently reported cause of adverse drug reactions. Isolated adverse drug reactions to Clavulanate, a β -lactamase inhibitor added to Amoxicillin to form amoxicillin-clavulanate, remain rarer. A 62-year-old male heart transplant candidate due to complicated coronary artery disease presented with a previous anaphylactic reaction secondary to amoxicillin-clavulanate for a sinus infection. Skin testing to penicillin G, penicilloate, benzylpenicilloyl polylysine and amoxicillin was negative, followed by a negative oral provocation test to amoxicillin. At a subsequent visit, the patient had negative skin testing to non-irritant concentrations of amoxicillin-clavulanate (20 mg/ml) and ampicillin-sulbactam (20 mg/ml). Clavulanate without amoxicillin was not available for testing. However, upon oral challenge with full-dose amoxicillin-clavulanate, he developed urticaria on his upper back, left upper extremity (Figure 1) and chest and experienced bilateral hand flushing that resolved over the course of two hours with the administration of IM diphenhydramine, fexofenadine and montelukast. The patient was counseled to avoid all forms of β -lactamase inhibitors and use equally efficacious alternatives. While IgE-mediated hypersensitivity reactions to penicillin are more common, IgE-mediated hypersensitivity reactions to β-lactamase inhibitors, including clavulanate, sulbactam, and tazobactam in isolation, have been reported. This case depicts an isolated β-lactamase inhibitor IgE-mediated reaction in the setting of previously negative skin testing.

PL03: Prophylactic administration of diphenhydramine to reduce neuroleptic side-effects in the acute care setting: a systematic review and meta-analysis

Introduction: Neuroleptics are commonly used drugs to treat different conditions (e.g. psychosis, migraines) in the acute care setting and the emergency department. Their side effects can be disabling or, worse, fatal. The use of diphenhydramine to prevent those side-effects is widespread, but remains controversial. We performed a systematic review to determine if prophylactic administration of diphenhydramine (PAD) reduces the incidence of neuroleptic side-effects. Methods: Data sources: Medline, Embase, Cochrane Library, PsycInfo and Web of Science were searched. References from reviews that were identified in the search and from included studied were also reviewed for inclusion. Study selection: Randomized controlled trials evaluating any neuroleptic with PAD versus the same neuroleptic alone or with any inactive agent. Primary outcome was incidence of any extra-pyramidal side-effect. Secondary outcomes were akathisia, usage of rescue medication, subjective restlessness, neuroleptic malignant syndrome, sedation and sedation intensity. Data extraction: Independent reviewers scanned identified citations, extracted data and assessed for risk of bias. Data analysis: Meta-analysis was performed using random effect models. Heterogeneity and quality of evidence were assessed using, respectively, I2 and the GRADE approach. Results: Results: Of 1566 identified citations, nine studies (n=1436) met all eligibility criteria. Four studies were specifically designed to assess for neuroleptic side-effects. Four studies were at high risk of bias. In primary analysis, PAD had no effect on the incidence of extra-pyramidal symptoms (7 studies, n=1393 patients, RR 0.70 [0.40-1.22]), akathisia (5 studies, n=1094 patients, RR 0.81 [0.36-1.82]) and sedation (5 studies; n=1079, RR 1,48 [0.90-2.42]). Higher dosage of diphenhydramine was not associated with a greater reduction of extra-pyramidal side-effects. In a sensitivity analysis excluding an outlier study (n=120, RR 6.63 [1.55-28,35]), PAD was associated with a significant decrease in extra-pyramidal side-effects (6 studies, n=1273, RR 0.56 [0,38-0.82]), but not with any of the secondary outcome measures. Conclusion: Conclusion: When excluding an outlier study, PAD was associated with a significant reduction of extra-pyramidal side-effects. However, PAD did not significantly influence the incidence of akathisia. Overall quality of evidence is low. Further studies are warranted. PAD represents an interesting treatment option against neuroleptic side-effects, but its widespread usage whitout strong evidence to support it raises concerns.

Use of diphenhydramine as an adjunctive sedative for colonoscopy in patients on chronic opioid therapy: a randomized controlled trial

Chronic opioid use increases tolerance to sedatives. Diphenhydramine is recommended for difficult-to-sedate patients during endoscopic procedures. We hypothesized that the addition of diphenhydramine to midazolam and fentanyl would improve objective and subjective measures of procedural sedation. This randomized, double-blind, placebo-controlled trial included patients on chronic opioids undergoing colonoscopy. Patients were randomized to receive 50 mg of diphenhydramine intravenously (n= 61) or placebo (n= 58), in addition to fentanyl and midazolam. Baseline characteristics, amount of fentanyl and midazolam, procedure times, and adverse events were recorded. Quality of sedation was assessed by the physician and nurse. Patients rated pain and amnesia on a 10-point scale. There was no difference in amounts of fentanyl (125.4 ± 56.2 μg vs 126.9 ± 53.5 μg, P= .88) and midazolam (4.9 ± 2.1 mg vs 5 ± 1.9 mg, P= .79) used. The mean sedation scores from the physician (6.2±1.1 vs 5.3 ± 1.2, P=.0002) and nurses (5.6 ± 1.5 vs 5.1 ± 1.4, P=.04) were statistically significant in favorof the diphenhydramine arm. Patient scores for pain (2.05 ± 2.17 vs 3.09 ± 3.95, P=.047) and amnesia (7.8±3.4 vs 6.5 ± 3.8, P=.047) favored the group that received diphenhydramine. Qualitative assessment showed no significant difference between the groups. There was no difference in induction time (P= .86), procedure duration (P= .98), or recovery time (P= .16). Hypotensive episodes were more common in the placebo group (P=.027). In patients on chronic opioid therapy, administration of diphenhydramine does not allow for lower doses of procedural sedatives but improves quality of sedation without increasing the number of adverse events. (Clinical trial registration number: NCT T01967433.).