Occurrence of hemodynamic changes following administration of rocuronium in a dog presenting for an ophthalmic procedure.

A 10-year-old, neutered male, Golden Retriever dog presented for surgical correction of a descemetocele. Acepromazine (0.02 mg/kg) and methadone (0.5 mg/kg) were administered intramuscularly for sedation, propofol (2 mg/kg) and midazolam (0.2 mg/kg) were administered intravenously for anaesthetic induction and isoflurane in oxygen was utilised for anaesthetic maintenance. Rocuronium (0.5 mg/kg), a neuromuscular blocking agent, was administered intravenously to facilitate central positioning of the eye for surgery. Within 10 min of rocuronium administration, the dog became tachycardic and hypotensive. Hemodynamic aberrations did not resolve with initial interventions but were successfully mitigated with the administration of diphenhydramine (0.8 mg/kg) intravenously. The dog remained stable throughout the remainder of the procedure and experienced a smooth and uneventful recovery. While it is difficult to confirm that the hemodynamic changes observed in this clinical case resulted solely from administration of rocuronium, the observance of the cardiovascular changes, timing of events and response to therapy suggest that rocuronium elicited a histamine response that was successfully treated with diphenhydramine.

Localized muscle spasm as a manifestation of pembrolizumab-induced infusion reaction.

INTRODUCTION: As immune checkpoint inhibitors increasingly gain oncological utility, the incidence of unique adverse events may rise as well. The description and management of localized, recurrent muscle spasms secondary to pembrolizumab infusions has not previously been reported. CASE REPORT: A 64-year-old male receiving pembrolizumab infusions experienced acute-onset, isolated spasms and pain occurring in cycles 2 through 5.Management and outcome: Pretreatment with intravenous lorazepam, diphenhydramine, famotidine, ondansetron, and fluids have led to spasm-free pembrolizumab infusions. DISCUSSION: The purpose of this report is to provide the first known incidence and successful corrective measures taken for localized muscle spasms secondary to pembrolizumab infusion.

Premedication with montelukast and rupatadine decreased rituximab infusion time, rate, severity of reactions and use of rescue medications.

Rituximab-associated infusion reactions (IRs) are significant burdens on oncology patients, caregivers and healthcare providers. We evaluated whether montelukast and rupatadine improve rituximab delivery, decrease frequency/severity of IRs and the number of medications used to control IRs. Using a nonrandomized clinical study design, we assessed adult rituximab naïve patients with B-cell lymphoid malignancies from January 2017 to July 2019. Prior to the first rituximab infusion patients received one of the premedication regimens: (i) standard premedications, diphenhydramine hydrochloride and acetaminophen ("SP" group); (ii) SP + montelukast ("M" group); (iii) SP + rupatadine ("R" group); (iv) SP + rupatadine + montelukast Schedule 1 ("M + R Schedule 1" group); (v) SP + rupatadine + montelukast Schedule 2 ("M + R Schedule 2" group). A total of 223 patients with a median age of 69 years were assessed. Demographics and treatment groups were comparable among all five groups. Mean rituximab infusion time was 290 min in the SP group versus 273, 261, 243 and 236 min in the M, R, M + R Schedule 1 and M + R Schedule 2 groups, respectively. The incidence of rituximab IRs was 75% in the SP group versus 44, 41, 22 and 22% in the M, R, M + R Schedule 1 and M + R Schedule 2 groups, respectively. The median reaction grade was 2 in the SP group and 0 in all other groups. The median number of rescue medications was 3 in the SP group and 0 in all other groups. In conclusion, montelukast and rupatadine significantly improved rituximab delivery, decreased the rate and severity of IRs and reduced the need for rescue medications.

The Influence of Adding Diphenhydramine Before Initiation of Moderate Sedation with Midazolam and Pethidine for Improving Quality of Colonoscopy.

BACKGROUND: Combination of Intravenous benzodiazepines with opiates appears to be essential in order to guarantee high quality of moderate sedation during colonoscopy. Diphenhydramine is recommended for endoscopic procedures in difficult-to-sedate patients However, the studies supporting its use have yielded conflicting results. OBJECTIVE: To assess the value of adding diphenhydramine hydrochloride before initiation of moderate sedation with midazolam and pethidine for Improving Quality of Sedation during colonoscopy. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled study of 150 Patients undergoing diagnostic colonoscopy. Of 150 patients, data were analyzed for 100 patients randomized into two groups: Diphenhydramine group (n = 53) received 50 mg of diphenhydramine intravenously before initiation of moderate sedation with pethidine and midazolam while in placebo group (n = 47) received placebo in addition to pethidine and midazolam. Amount of pethidine and midazolam used and Quality of sedation were assessed. RESULTS: The mean doses of pethidine was significantly higher in placebo group as compared to diphenhydramine group (69.9 ± 35.4 mg vs 61.2 ± 21.0 mg, p < 0.01) However, no significant difference between the two groups regarding midazolam mean dose (4.9.±2.1 mg vs 4.8 ± 2.0 mg,p = 0.786). More patients in diphenhydramine group were being very satisfied with the procedure as compared to those in placebo group (88.67% vs 59.57%,p < 0.001).Furthermore more endoscopist in diphenhydramine group were being very satisfied with the procedure as compared to those in placebo group (77.35% vs 51.06%,p < 0.001). CONCLUSIONS: Intravenous diphenhydramine hydrochloride given before initiation of midazolam and pethidine offers a significant Improvement of Quality of moderate Sedation during colonoscopy without increasing the number of sedation related complications.

Successful mast-cell-targeted treatment of chronic dyspareunia, vaginitis, and dysfunctional uterine bleeding.

Dyspareunia, vaginitis and dysfunctional uterine bleeding (DUB) are common problems which, despite their polygenicity, commonly appear idiopathic and treatment-refractory. Mast cell (MC) activation syndrome (MCAS) is a newly-recognised, prevalent, chronic multisystem polymorbidity of general themes of inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues. MCs produce significant quantities of heparin, too. As such, MCAS may underlie some cases of chronic dyspareunia, vaginitis or DUB. We report five such patients; all who responded well to MC-targeted treatment. We review aspects of MC biology and pathobiology of potential relevance to otherwise idiopathic persistent inflammatory or coagulopathic genital tract problems. Diagnostic testing for MCAS may be warranted in some patients with chronic dyspareunia, vaginitis or DUB (especially patients whose histories well fit the general profile of MCAS), and prospective therapeutic trials of MC-directed topical and/or systemic therapies may be warranted in such populations. Impact statement What is already known on this subject? Chronic, idiopathic, treatment-refractory female genital tract inflammation or bleeding are common problems for which mast cell (MC) disease, previously generally thought to consist of just rare cases of mastocytosis, and is seldom considered in the differential diagnosis. What do the results of this study add? The substantial prevalence of the newly recognised 'mast cell activation syndrome' (MCAS), featuring chronic inappropriate MC activation with little-to-no MC neoplasia, and its clinical presentation with chronic multisystem inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues, raises the possibility that MCAS might underlie the aforementioned genital tract problems, especially in patients whose larger clinical presentations fit the MCAS profile. We report five example patients (among many more we have similarly treated) who enjoyed excellent responses to safe, inexpensive MC-targeted treatments, often given just intravaginally. What are the implications of these findings for clinical practice and/or further research? Our report identifies a potentially significant new MC-focused direction, of relevance to millions of affected women worldwide, for clinical treatment as well as for basic and clinical research, which historically has yielded major advancements disappointingly disproportionate to the scope of the affected population.

The feasibility of dexamethasone omission in weekly paclitaxel treatment for breast cancer patients.

OBJECTIVES: Patients with breast cancer who receive weekly paclitaxel therapy may experience deleterious effects associated with prophylactic dexamethasone use for 12 consecutive weeks. Approximately 90% of paclitaxel hypersensitivity reactions (HSRs) occur within the first 10 to 15 min of the first two infusions. We investigated the feasibility of dexamethasone withdrawal between weeks 3 and 12 (W3 and W12) in early stage breast cancer patients treated with weekly paclitaxel at the standard dose (80 mg/m2). METHODS: All patients received intravenous prophylaxis of dexamethasone 20 mg, ranitidine 50 mg, and diphenhydramine 50 mg in the first 2 weeks (W1 and W2) of treatment. Provided that no serious (G3/G4) HSRs events occurred, dexamethasone was omitted between W3 and W12, while ranitidine and diphenhydramine were continued. The primary end point was the incidence of any grade HSRs during the treatment period, and the secondary end points were quality of life and weight changes. RESULTS: Twenty-five patients were included in the study, and 300 infusion cycles of paclitaxel were evaluated for HSRs. The overall incidence of HSRs was 0.6% (2 events), and both of these events occurred in the first week. There were no incidents of serious HSRs or anaphylaxis and no G3 or G4 toxicities. Scores from the EORTC QLQ-C30 questionnaire did not change significantly for the global health status/quality of life scale or for the symptoms scales, although changes in scores differed significantly for the functional scales. There were no clinically relevant weight changes during the treatment period. CONCLUSIONS: Dexamethasone withdrawal from W3 to W12 in early stage breast cancer patients treated with weekly paclitaxel is feasible. The incidence of all grades of HSRs was comparable to that reported in trials with dexamethasone for 12 consecutive weeks, and no serious events (G3/G4) occurred. Studies with larger sample sizes are needed to confirm our results which are important, especially for patients for whom corticosteroids are contraindicated.

Reduction in ocrelizumab-induced infusion reactions by a modified premedication protocol.

BACKGROUND: Ocrelizumab is a monoclonal antibody directed against CD20+ B cells that is approved for MS. The most common side effect is infusion-associated reactions (IARs). This study examines whether a modified premedication protocol reduces incidence of IARs and further examines predictors of IARs. METHODS: Patients took cetirizine 10 mg, ranitidine 75 mg, and increased hydration the night before the ocrelizumab infusion. This regimen was repeated the next day prior to arrival. Just prior to the infusion, patients were pretreated with IV diphenhydramine 50 mg, IV methylprednisolone 125 mg, and oral acetaminophen 650 mg. Rates of IARs with this modified protocol were compared to patients who had received only pretreatment medications. RESULTS: 207 patients received ocrelizumab. With the modified premedication protocol, we found significant decreased odds of IARs (OR 0.40, p = 0.024, 95% CI (0.18, 0.88). Among the baseline characteristics, there was a significant reduction of IARs with increasing age (OR 0.94, p = 0.001) and male sex (OR 0.34, p = 0.034). Body mass index (BMI) increased the odds of IARs (OR 1.07, p = 0.029). Race and smoking status did not affect IARs. CONCLUSION: The modified premedication protocol described herein significantly decreases rates of IARs by 60% and suggests that the additional premedication regimen is beneficial. Age and male sex are protective for IARs while BMI is a risk factor for IARs.

Impact of fellowship training level on colonoscopy quality and efficiency metrics.

BACKGROUND AND AIMS: Previous studies have described variable effects of fellow involvement on the adenoma detection rate (ADR), but few have stratified this effect by level of training. We aimed to evaluate the "fellow effect" on multiple procedural metrics including a newly defined adenoma management efficiency index, which may have a role in documenting colonoscopy proficiency for trainees. We also describe the impact of level of training on moderate sedation use. METHODS: We performed a retrospective review of 2024 patients (mean age, 60.9 ± 10 years; 94% men) who underwent outpatient colonoscopy between June 2012 and December 2014 at our Veterans Affairs Medical Center. Colonoscopies were divided into 5 groups. The first 2 groups were first-year fellows in the first 6 months and last 6 months of the training year. Second- and third-year fellows and attending-only procedures accounted for 1 group each. We collected data on doses of sedatives used, frequency of adjunctive agent use, procedural times, and location, size, and histology of polyps. We defined the adenoma management efficiency index as average time required per adenoma resected during withdrawal. RESULTS: Of the colonoscopies performed, 1675 involved a fellow and 349 were performed by the attending alone. There was no difference in ADR between fellows according to level of training (P = .8) or between fellows compared with attending-only procedures (P = .67). Procedural times decreased consistently during training and declined further for attending-only procedures. This translated into improvement in the adenoma management efficiency index (fellow groups by ascending level of training: 23.5 minutes vs 18.3 minutes vs 13.7 minutes vs 13.4 minutes vs attending group 11.7 minutes; P < .001). There was no difference in the average doses of midazolam and fentanyl used among fellow groups (P = .16 and P = .1, respectively). Compared with attending-only procedures, fellow involvement was associated with higher doses of fentanyl and midazolam and more frequent use of diphenhydramine and glucagon (P < .0001, P = .0002, P < .0001, and P = .01, respectively). CONCLUSIONS: ADR was similar at different stages of fellowship training and comparable with the attending group. Efficiency of detecting and resecting polyps improved throughout training without reaching the attending level. Fellow involvement led to a greater use of moderate sedation, which may relate to a longer procedure duration and an evolving experience in endoscopic technique.

Beyond-use dating of lidocaine alone and in two "magic mouthwash" preparations.

PURPOSE: Beyond-use dating (BUD) of lidocaine alone and in two "magic mouthwash" preparations stored in amber oral syringes at room temperature was determined. METHODS: Two formulations of mouthwash containing oral topical lidocaine 2% (viscous), diphenhydramine 2.5 mg/mL, and aluminum hydroxide-magnesium hydroxide-simethicone were prepared in 1:1:1 and 1:2.5:2.5 ratios, divided into 3-mL samples, and stored in unit-dose oral amber syringes. Unit-dose single-product lidocaine samples were also prepared to serve as controls and stored in oral amber syringes. The lidocaine concentrations in these samples were measured periodically for 90 days. A stability-indicating high-performance liquid chromatographic method was developed and validated for system suitability, accuracy, repeatability, intermediate precision, specificity, linearity, and robustness. RESULTS: Based on the calculated percentages versus the initial concentration and the results from an analysis of variance comparing the two formulations, a BUD of 21 days is deemed appropriate for both magic mouthwash formulations. Based on the stability data, published safety concerns, and lack of efficacy in combination, packaging and dispensing lidocaine separately from other ingredients are recommended when administering magic mouthwash mixtures. Utilizing a 90-day BUD, lidocaine can be packaged separately from other magic mouthwash ingredients in individual dosage units and applied to the oral cavity using the swish-and-spit method. The delivery of the diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone could be separated, allowing for a swish-and-swallow method of administration. CONCLUSION: A BUD of 21 days is recommended for lidocaine prepared with diphenhydramine and aluminum hydroxide-magnesium hydroxide-simethicone in ratios of 1:1:1 and 1:2.5:2.5 and stored at room temperature in amber oral plastic syringes.

Continuous diphenhydramine infusion and imatinib for KIT-D816V-negative mast cell activation syndrome: a case report.

BACKGROUND: We present the first full case report of the treatment of mast cell activation syndrome with continuous diphenhydramine infusion, which resulted in the improvement of anaphylactic reactions and a decrease in hospital readmission. Furthermore, the patient received imatinib in the absence of the KIT-D816V mutation, which led to further improvement of quality of life. Currently, we are trying to wean this patient off diphenhydramine; if successful, this attempt will represent the first reported case. CASE PRESENTATION: An 18-year-old white girl presented with a flare of mast cell activation syndrome and received epinephrine and steroids. She had failed multiple previous therapies, and her quality of life was affected due to two to three flares/week. She was started on continuous diphenhydramine infusion and imatinib, which led to a decrease in hospital admissions and marked improvement in her quality of life. CONCLUSIONS: Continuous diphenhydramine infusion can provide promising outcomes following the failure of intermittent antihistamine dosing in patients with severe mast cell activation syndrome. Initiating continuous diphenhydramine infusion may be helpful in an intensive care setting when the patient is particularly prone to anaphylaxis and/or the resources needed to manage anaphylaxis are not available outside the intensive care unit. Furthermore, imatinib provides benefits in KIT-D816V-negative mast cell disorders due to other unknown mutations.

Injectable Diphenhydramine Used as Anaesthetic for Wide Local Excision With Flap Closure.

BACKGROUND: Lidocaine-allergic patients pose a challenge for cutaneous surgical procedures. We present a case of a successful wide local excision with flap closures on the face using topical tetracaine followed by infiltration with 1% diphenhydramine. CASE SUMMARY: An 84-year-old woman, with a lidocaine intolerance, presented to the Mohs surgery clinic for wide local excision of a nodular basal cell carcinoma on her right medial cheek. Successful anaesthesia was achieved using topical 4% tetracaine followed by intradermal and subcutaneous injection of 1% diphenhydramine. Haemostasis was achieved with both electrocautery and suture ligation. Sliding rotation flaps were closed using both deep and superficial sutures. Other than some mild discomfort and temporary hyperemia on injection, the patient tolerated the procedure well with no long-term complications. CONCLUSION: Diphenhydramine is a very useful alternative in lidocaine-intolerant patients for cutaneous procedures including punch and shave biopsies, cyst removals, small elliptical excisions, and wide local excisions.

Dose-ranging effect of systemic diphenhydramine on postoperative quality of recovery after ambulatory laparoscopic surgery: a randomized, placebo-controlled, double-blinded, clinical trial.

STUDY OBJECTIVE: Diphenhydramine is an antihistamine with previously demonstrated analgesic and antiemetic properties. However, it is unknown if the beneficial perioperative properties of diphenhydramine can translate to a better quality of postsurgical recovery. The main objective of the current investigation was to investigate dose-ranging effects of diphenhydramine on quality of recovery after surgery. SETTING: Tertiary hospital in the United States. DESIGN: A prospective, randomized, double-blind trial. INTERVENTION: Saline, diphenhydramine 25 >mg, or diphenhydramine 50 mg given intravenously before induction. MEASUREMENTS: The primary outcome was global Quality of Recovery-40 at 24hours. Postoperative pain, nausea, opioid consumption, and discharge time were also evaluated. MAIN RESULTS: Ninety subjects were randomized, and 75 completed the study. The median (interquartile range) Quality of Recovery-40 scores were not different among study groups: 164 (151-189), 169 (159-181), and 172 (157-185) for the saline, 25-mg diphenhydramine, and 50-mg diphenhydramine groups, respectively (P=.74). Postoperative nausea was decreased in the 50-mg group, 3 of 24 (12.5%), compared with the saline group, 12 of 27 (44%), P=.01. There was an inverse linear association between postoperative opioid consumption and quality of recovery (R(2)=0.37, P<.001). CONCLUSIONS: Diphenhydramine does not provide dose-ranging improvements on postoperative quality of recovery after ambulatory laparoscopic gynecologic surgery. Our results support a recent concept that not all postoperative nausea and vomiting symptoms are clinically important. Future studies evaluating postoperative nausea and vomiting should include patient-centered outcomes to validate the clinical importance of the examined interventions.

The pharmacokinetics of DPH after the administration of a single intravenous or intramuscular dose in healthy dogs.

The objective of this study was to determine the pharmacokinetics of diphenhydramine (DPH) in healthy dogs following a single i.v. or i.m. dose. Dogs were randomly allocated in two treatment groups and received DPH at 1 mg/kg, i.v., or 2 mg/kg, i.m. Blood samples were collected serially over 24 h. Plasma concentrations of DPH were determined by high-performance liquid chromatography, and noncompartmental pharmacokinetic analysis was performed with the commercially available software. Cardio-respiratory parameters, rectal temperature and effects on behaviour, such as sedation or excitement, were recorded. Diphenhydramine Clarea , Vdarea and T1/2 were 20.7 ± 2.9 mL/kg/min, 7.6 ± 0.7 L/kg and 4.2 ± 0.5 h for the i.v. route, respectively, and Clarea /F, Vdarea /F and T1/2 20.8 ± 2.7 mL/kg/min, 12.3 ± 1.2 L/kg and 6.8 ± 0.7 h for the i.m. route, respectively. Bioavailability was 88% after i.m. administration. No significant differences were found in physiological parameters between groups or within dogs of the same group, and values remained within normal limits. No adverse effects or changes in mental status were observed after the administration of DPH. Both routes of administration resulted in DPH plasma concentrations which exceeded levels considered therapeutic in humans.

Medication-induced acute dystonic reaction: the challenge of diagnosing movement disorders in the intensive care unit.

A 62-year-old man presented with left middle cerebral artery stroke. 1 h postadministration of tissue plasminogen activator, he received a total of 4 mg of haloperidol for combativeness. He developed partial complex status epilepticus, requiring benzodiazepines, phenytoin, propofol and intubation. 5 h later, he developed recurrent stereotyped tonic movements involving arching of the back, extension of the arms and contraction of opposing muscle groups. Repeat CT scan of the head showed evolving insular infarct. Differential diagnoses for these movements included tonic/clonic seizures, extensor (decerebrate) posturing from haemorrhagic conversion, neuroleptic malignant syndrome, or dystonic reaction. Given the lack of response to antiseizure medications, the recent administration of haloperidol, and the prompt resolution of movements following diphenhydramine administration, an acute dystonic reaction was considered. This atypical case of a critically ill patient with stroke highlights the fact that these patients may have multiple abnormal movements requiring careful analysis to guide diagnosis-specific management.

Urticaria pigmentosa-like disease in a dog.

Urticaria pigmentosa is a rare dermatologic syndrome in humans, cats, and dogs. This report documents a case of canine urticaria pigmentosa-like disease with unusual features and no C-kit mutation.

Maladie s'apparentant à l'urticaire pigmentaire chez un chien. L'urticaire pigmentaire est un syndrome dermatologique rare chez les humains, les chats et les chiens. Ce rapport documente un cas canin s'apparentant à l'urticaire pigmentaire comportant des caractéristiques inhabituelles et l'absence de mutation C-kit.(Traduit par Isabelle Vallières).

Stopping paclitaxel premedication after two doses in patients not experiencing a previous infusion hypersensitivity reaction.

PURPOSE: Paclitaxel-based chemotherapy continues to be an integral component of breast cancer treatment. Prolonged use of paclitaxel may result in repeated doses of premedications that can have unwanted side effects. Infusion hypersensitivity reactions occurring beyond the second dose of paclitaxel are infrequent and not well characterized. We previously published the results of a small, prospective pilot trial demonstrating the safety and feasibility of discontinuing premedications in patients who received the first two doses of paclitaxel-based chemotherapy without experiencing an infusion hypersensitivity reaction. In this study, we aimed to retrospectively characterize the incidence of rescue medication using this abbreviated premedication regimen in our institution following the publication of the pilot study. METHODS: Patients with stages I-IV breast cancer who received paclitaxel from January 2011 through June 2013 were screened for eligibility. Patients who did not experience an infusion hypersensitivity reaction with their first or second dose of paclitaxel and discontinued paclitaxel premedication for subsequent doses were included in this analysis. The primary endpoint was to estimate the incidence of rescue medication use for the treatment of paclitaxel infusion hypersensitivity during doses three to six of paclitaxel in the study population. RESULTS: In total, 449 patients received paclitaxel-based chemotherapy for the treatment of breast cancer during the interval time period. After receiving the first two doses of paclitaxel-based chemotherapy without experiencing an infusion hypersensitivity reaction, 234 breast cancer patients had their premedications discontinued for all remaining paclitaxel doses. These patients tolerated future paclitaxel doses without severe or life-threatening complications related to infusion hypersensitivity. The majority of patients did not have any symptoms of an infusion reaction, with only two of these patients requiring rescue medication to treat an infusion hypersensitivity reaction with subsequent paclitaxel doses (0.85; 95 % confidence interval (CI), 0.10-3.05 %). CONCLUSIONS: Discontinuation of paclitaxel premedications in breast cancer patients who have not experienced an infusion hypersensitivity reaction with the first two doses of paclitaxel is not associated with increased rate of rescue medication use for infusion hypersensitivity.