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.

Marijuana and endoscopy: the effects of marijuana on sedation.

BACKGROUND AND AIMS: Marijuana usage has increased significantly as it has become more readily available and legal, either recreationally or medicinally, in many states. It has been postulated that marijuana usage increases the amount of sedation required for procedures. However, there are minimal data defining this relationship. We aimed to establish the relationship between marijuana usage and the amount of sedation used during endoscopy. METHODS: This was a single-institution prospective study of patients undergoing outpatient endoscopy (both monitored anesthesia care [MAC] and moderate sedation) at the Oklahoma City Veterans Affairs Medical Center. Marijuana usage was assessed by a voluntary de-identified pre-endoscopy survey. Information regarding sedation used, endoscopy outcomes, demographics, comorbidities, medical history, and medications used was extracted from the medical record. A univariate and stratified analysis of alcohol usage was performed. A P value of <.05 was considered to be significant. RESULTS: A total of 976 patients were analyzed; 21.5% of them endorsed marijuana usage (210/976). Marijuana users were found to be younger (P = .0002), leaner (P < .0001), and less likely to have diabetes (P = .002), obstructive sleep apnea (P = .0002), and hypertension (P = .04). They were also more likely to smoke (P < .0001) and vape (P < .0001). Marijuana usage was associated with a higher requirement of sedation (fentanyl [P = .003], midazolam [P = .05], propofol [P = .02]) and higher use of adjunct sedation (diphenhydramine in moderate sedation [P = .0003]). Further multivariate analyses were performed to control for possible confounders. Marijuana usage was still deemed to be an independent predictor for high propofol use among MAC cases (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.00-3.12). Likewise, marijuana usage was found to be an independent predictor for high midazolam use (OR, 1.57; 95% CI, 1.02-2.42) and high fentanyl use (OR, 1.54; 95% CI, 0.98-2.38), but failed to reach statistical significance in the fentanyl group. CONCLUSIONS: Marijuana use is associated with a significantly higher amount of sedation along with a significantly higher usage of other adjunct sedatives. A patient's marijuana history should be considered when determining the methods of sedation to be used for endoscopy.

Operational outcomes of propofol sedation versus fentanyl, midazolam and diphenhydramine sedation for endoscopies and colonoscopies at an academic medical center.

BACKGROUND: On July 1st, 2021, the University of Colorado Hospital (UCH) implemented new sedation protocols in the luminal gastrointestinal (GI) suite. GI proceduralist supervised, Nurse Administered Sedation with fentanyl, midazolam, and diphenhydramine (NAS) sedation was transitioned to Monitored Anesthesia Care with propofol under physician anesthesiologist supervision (MAC). OBJECTIVE: To determine if there are statistically significant reductions in Sedation-Start to Scope-In time (SSSI) when using Monitored Anesthesia Care with propofol (MAC) versus Nurse Administered Sedation with fentanyl, midazolam, and diphenhydramine (NAS). Secondary objectives were to determine if statistically significant improvements to other operational times, quality measures, and satisfaction metrics were present. METHOD: This study was a retrospective analysis of a natural experiment resultant of a change from NAS to MAC sedation protocols. Outcomes for NAS protocols from 1/1/21-6/30/21 were compared to outcomes of MAC protocols from the dates 8/1/21-10/31/21. Results were analyzed using Quasi-Poisson regression analysis and stratified based on upper GI, lower GI, and combined procedures. Patient demographic data including age, biological sex, comorbidities, and BMI, were adjusted for in the analysis. ASA matching was not performed as nursing sedation does not use ASA classifications. Pre-anesthesia co-morbidities were assessed via evaluation of a strict set of comorbidities abstracted from the electronic medical record. Perioperative operational outcomes include Sedation Start to Scope-In (SSSI), In-Room to Scope-In Time (IRSI), Scope Out to Out of Room (SOOR), Total Case Length (TCL), and Post Anesthesia Care Unit Length of Stay (PACU LOS). Quality outcomes include PACU Administered Medications (PAM), and Clinician Satisfaction Scores (CSS). RESULTS: A total of 5,582 gastrointestinal (GI) endoscopic cases (upper, lower, and combined endoscopies) were observed. Statistically significant decreases in SSSI of 2.5, 2.1, and 2.2 minutes for upper, lower, and dual GI procedures were observed when using MAC protocols. A statistically significant increase in satisfaction scores of 47.0 and 19.6 points were observed for nurses and proceduralists, respectively, when using MAC. CONCLUSION: MAC protocols for endoscopic GI procedures at UCH led to statistically significant decreases in the time required to complete procedures thus increasing operational efficiency.

Retrospective review of diphenhydramine vs diphenhydramine plus glucocorticoid for the treatment of allergic reaction in cats.

OBJECTIVES: The aims of the present study were to report the outcomes of treating allergic reactions in cats with diphenhydramine vs diphenhydramine plus glucocorticoid and to determine whether signs recurred or additional veterinary intervention was needed in the days after initial treatment. METHODS: This retrospective study evaluated 73 cats treated for allergic reaction with diphenhydramine alone or in combination with a glucocorticoid at a 24 h emergency and specialty referral veterinary hospital between 1 January 2012 and 31 March 2021. RESULTS: In total, 44 cats were treated with diphenhydramine alone, and 29 were treated with diphenhydramine plus dexamethasone sodium phosphate. The inciting cause was known or highly suspected in 50 patients. Vaccines were the most common (31 patients), followed by insect envenomation (17 cases). No cat in either group progressed to anaphylaxis. There was no difference in resolution of clinical signs between the groups. Follow-up contact was successfully made with 40/73 cat owners. All 40 cats were alive. Eight had persistent signs. There was no difference in the number of cats with persistent signs between groups. Five cats required additional treatment after the initial emergency visit. There was no difference between the two groups for persistent signs at follow-up. CONCLUSIONS AND RELEVANCE: There was no difference in measured outcomes between cats treated with diphenhydramine alone vs those treated with a glucocorticoid in addition to diphenhydramine in this population. The ideal treatment for allergic reactions is unknown. Based on currently available data in human and veterinary literature, glucocorticoids are not indicated to treat acute allergic reactions. The role of antihistamines as part of a symptomatic supportive treatment plan to shorten the duration of signs is unclear at this time and may be considered.

Comparison of the preventive effect of colchicine versus diphenhydramine, prednisolone, and a combination therapy on intraperitoneal adhesion bands: an experimental study in rats.

BACKGROUND: Peritoneal adhesion formation is an inevitable consequence of abnormal repair of the peritoneum following different peritoneal injuries of intra-abdominal operations with the subsequent morbidity that they represent. Vast efforts have been made to elucidate the cause and prevent the development of abdominal adhesions. The aim of our study is to compare the capability of colchicine versus diphenhydramine (DPH) and methylprednisolone (MP), and also prednisolone in adhesion prevention. METHODS: Sixty-one male Wistar stock rats were divided into four groups. The first group attended as the control group. Groups 2, 3, and 4 received oral combination of MP + DPH solution (20 mg/kg), colchicine (0.02 mg/kg), and prednisolone (1 mg/ kg), respectively. Adhesion bands were induced by standardized abrasion of the peritoneum through a midline laparotomy. All rats were sacrificed on the 15th-day post medication administration and the subjects underwent an exploratory laparotomy. The presence of adhesions was evaluated with the modified using Nair's classification. RESULTS: The proportion of the control group with substantial adhesion bands (73.3%) was significantly higher than that of the MP + DPH (13.3%), colchicine (33.3%), and prednisolone (31.3%) groups. There were significant differences between the scores of the control and the MP + DPH, colchicine, and prednisolone groups (P = 0.001, 0.028, and 0.019, respectively). There was no statistically significant difference to favor colchicine against MP + DPH (P = 0.390) or MP + DPH against prednisolone (P = 0.394). CONCLUSIONS: Both colchicine and combination of DPH + MP prevented postoperative abdominal adhesions separately in our study. However, the lowest adhesion formation rate was observed in the DPH + MP group, even lower than the prednisolone group.

Safety and technical success of diphenhydramine as an alternative local anaesthetic agent for radiology procedures.

AIM: To evaluate retrospectively the safety and technical success of subcutaneous diphenhydramine as an alternative local anaesthetic for radiology procedures. MATERIALS AND METHODS: Between January 2000 and April 2021, 84 image-guided procedures were performed in 81 adult patients (mean age 61 years, 86% female) using 1% injectable diphenhydramine as a local anaesthetic. Indications were history of severe allergy to "-caine" local anaesthetics in 76 (90%) patients and recent administration of bupivacaine liposomal injectable suspension in eight (10%) patients. Twelve of the 84 (14%) procedures were performed with concomitant moderate sedation. Patient characteristics, procedural techniques, and clinical outcomes were reviewed. Early and delayed (30-day) complications were classified as either related to local diphenhydramine injection or to the procedure itself. Procedure-related complications were gradated using the Clavien-Dindo system. RESULTS: Percutaneous biopsy was the most frequently performed procedure (57/84, 67%). Fifty-nine (70%) of the 84 procedures were ultrasound guided. The most common procedural site was the breast (34/84, 40%). All procedures were technically successful. There were two minor injection-related complications related to post-procedural pain. A single minor procedure-related complication involved a patient requiring hospital admission for post-renal biopsy related haematuria. CONCLUSION: Injectable diphenhydramine appears to be a safe and effective local anaesthetic alternative in patients with "-caine" class contraindications undergoing radiology procedures. A future prospective trial would be useful to assess the safety profile in an large cohort of patients.

Classification of acute poisoning exposures with machine learning models derived from the National Poison Data System.

The primary aim of this pilot study was to develop a machine learning algorithm to predict and distinguish eight poisoning agents based on clinical symptoms. Data were used from the National Poison Data System from 2014 to 2018, for patients 0-89 years old with single-agent exposure to eight drugs or drug classes (acetaminophen, aspirin, benzodiazepines, bupropion, calcium channel blockers, diphenhydramine, lithium and sulfonylureas). Four classifier prediction models were applied to the data: logistic regression, LightGBM, XGBoost, and CatBoost. There were 201 031 cases used to develop and test the algorithms. Among the four models, accuracy ranged 77%-80%, with precision and F1 scores of 76%-80% and recall of 77%-78%. Overall specificity was 92% for all models. Accuracy was highest for identifying sulfonylureas, acetaminophen, benzodiazepines and diphenhydramine poisoning. F1 scores were highest for correctly classifying sulfonylureas, acetaminophen and benzodiazepine poisonings. Recall was highest for sulfonylureas, acetaminophen, and benzodiazepines, and lowest for bupropion. Specificity was >99% for models of sulfonylureas, calcium channel blockers, lithium and aspirin. For single-agent poisoning cases among the eight possible exposures, machine learning models based on clinical signs and symptoms moderately predicted the causal agent. CatBoost and LightGBM classifier models had the highest performance of those tested.

Use of tracking drugs for the search of intra-hospital adverse reactions: a pharmacovigilance study.

OBJECTIVE: To estimate the incidence of potential in-hospital adverse reactions  with the use of alert drugs in a general hospital in southern Brazil. Method: Cross-sectional study, carried out in a hospital in southern Brazil. The  electronic medical records (TASY®) of patients hospitalized between January  and August 2020, who were prescribed one of the drugs earmarked for  tracking adverse drug reactions, were evaluated: the drugs included  flumazenil, fexofenadine hydrochloride, naloxone, promethazine, diphenhydramine and loperamide. RESULTS: A total of 13,476 medical records were reviewed and 204 (1.5%)  were included in the study in which tracker use was indicated in the management of adverse drug reactions. In this study a total of 18 different signs or symptoms were found in medical records, with  pruritus/hyperemia/urticaria being the most reported symptoms (n = 76).  Among the drug classes that caused most adverse drug reactions, opioids were  the most mentioned (n = 44). It should be noted that in 49 medical  records the information on which drug caused the adverse events was not  reported. Regarding the cause of hospitalization of patients who used  creening drugs, cancer was the most frequent (n = 37). CONCLUSIONS: This study indicates that the use of trackers can be a tool to  estimate the occurrence of adverse drug reactions and to establish adverse  events related to the use of medications, which should be reported to the  pharmacovigilance service, with a view to patient safety.

OBJETIVO: Estimar la incidencia de potenciales reacciones adversas intrahospitalarias con el uso de prescripciones alertantes en un  hospital general del sur de Brasil.Método: Estudio transversal, realizado en un hospital del sur de Brasil. Se  evaluaron las historias clínicas electrónicas (TASY®) de los pacientes hospitalizados entre enero y agosto de 2020, a los que se les  prescribió uno de los medicamentos destinados al seguimiento de reacciones  adversas a medicamentos: los medicamentos incluían flumazenil, clorhidrato de fexofenadina, naloxona, prometazina, difenhidramina y  loperamida. RESULTADOS: Se revisaron 13.476 historias clínicas y se incluyeron 204 (1,5%) en el estudio en el que se indicó el uso de prescripciones alertantes en  el manejo de reacciones adversas a medicamentos. En este estudio se  encontró un total de 18 signos o síntomas diferentes en las historias clínicas,  siendo el prurito, la hiperemia y la urticaria los síntomas más reportados (n =  76). Entre las clases de fármacos que causaron la mayoría de las reacciones  adversas a medicamentos, los opioides fueron los más mencionados (n = 44).  Cabe señalar que en 49 historias clínicas no se reportó la información sobre  qué fármaco causó los eventos adversos. En cuanto a la causa de  hospitalización de los pacientes que utilizaron prescripciones alertantes, el  cáncer fue la más frecuente (n = 37). Conclusiones: Este estudio indica que el uso de alertadores puede ser una  herramienta para estimar la incidencia de reacciones adversas a medicamentos y establecer eventos adversos relacionados con el uso de medicamentos, los cuales deben ser reportados al servicio de  armacovigilancia, con miras a la seguridad del paciente.

Anaphylaxis due to First-Time Intravenous Infusion of N-Acetylcysteine in a Dog.

A 4-year-old female spayed Pomeranian was referred to the emergency service for intermittent trouble breathing and an enlarged liver found on ultrasound. A severe mixed hepatopathy was found on bloodwork, and ultrasound-guided liver aspirates showed marked hepatocellular vacuolar changes and rare neutrophils. An intravenous (IV) loading dose of n-acetylcysteine (NAC) was given for the first time in this patient, and immediately after the infusion the patient collapsed, became hypotensive, hypothermic, tachycardic, and developed gallbladder wall edema. Treatment for anaphylaxis was immediately initiated with IV fluids, an epinephrine bolus and then continuous rate infusion, diphenhydramine, and famotidine. Clinical signs resolved within an hour of treatment with no recurrence. The hepatic enzymopathy improved, and the patient was ultimately diagnosed with a steroid hepatopathy based on laparoscopic liver biopsies. Anaphylaxis caused by first-time administration of IV NAC in a dog has not previously been reported, though it is known to occur in humans. Based on this report, it would be clinically wise to give careful consideration before prescribing NAC in cases where it is not a specific antidote or if other options are available, and to closely monitor the patient during and immediately after administration.

Rates and types of urine drug screen false negative results compared with confirmatory toxicology testing in major trauma patients.

BACKGROUND: Trauma centers are required to screen patients for alcohol use, and if necessary, intervene and refer to treatment (SBIRT). Similar screening for illicit drug use is recommended but not required. Urine drug screening (UDS) underestimates problematic substance use. This study aimed to estimate the types and rates of UDS false negatives (FN) compared to comprehensive testing by liquid chromatography-mass spectrometry (LC-MS) in trauma patients. METHODS: We performed a prospective cohort study of deidentified urine samples from adult trauma and burn activation patients. Both UDS and LC-MS comprehensive testing of >200 analytes were performed by a reference laboratory on all samples. Iatrogenic medications were excluded from the FN count. Crosstab analyses were conducted for UDS versus LC-MS outcomes to establish FN types and rates. We dichotomized the results by creating an "intentionality" variable (intentional injuries by self/others versus accidental injuries). A series of crosstabs with odds ratios considered intentionality by substance class and demographics. Statistically significant variables by Chi-Square were assessed by logistic regression. RESULTS: Psychoactive FN were detected in 56/100 urine samples analyzed; the most frequent included anticonvulsants (primarily gabapentin, N = 13), opioid agonists (N = 12), antihistamines (primarily diphenhydramine, N = 10), and phenethylamines (primarily bupropion, N = 5). Nonpsychoactive FN were detected in 70/100 samples; the most common were nicotine (N = 33), caffeine (N = 23), acetaminophen (N = 22), and antidepressants (N = 12). Of substance classes included in the UDS and also tested by LC-MS, FN occurred for opiates (3%), amphetamines (5%) and opioids (25%). Polypharmacy was associated with fall injuries in elderly patients. Cocaine (p = 0.015) and cannabinoids (p = 0.002) were significantly associated with intentionality. CONCLUSIONS: Our results indicate that FN for potentially important psychoactive and nonpsychoactive substances are common when toxicologic testing is limited to routine UDS in trauma patients. We recommend expanding SBIRT in this patient population to include misuse of tobacco products, prescription analgesics, and over-the-counter antihistamines.

Integrated biomarker response in signal crayfish Pacifastacus leniusculus exposed to diphenhydramine.

Diphenhydramine (DPH) is a pharmaceutical with multiple modes of action, primarily designed as an antihistamine therapeutic drug. Among antihistamines, DPH is a significant contaminant in the environment, frequently detected in surface waters, sediments, and tissues of aquatic biota. In the present study, signal crayfish Pacifastacus leniusculus was used as a model organism because of their prominent ecological roles in freshwater ecosystems. The biochemical effects were investigated in crayfish exposed to the environmental (low: 2 µg L-1), ten times elevated (medium: 20 µg L-1), and the sublethal (high: 200 µg L-1) nominal concentrations of DPH in water for 96 h. Lipid peroxidation, antioxidant enzyme activities, and acetylcholinesterase activity were assessed as toxicological biomarkers in crayfish hepatopancreas, gills, and muscles. Low and medium DPH exposure caused imbalances only in glutathione-like enzyme activities. Integrated biomarker response showed the absolute DPH toxicity effects on all tested tissues under high exposure. This study identified that high, short-term DPH exposure induced oxidative stress in crayfish on multiple tissue levels, with the most considerable extent in muscles.

Uso de emulsiones lipídicas en el tratamiento exitoso de un caso de intoxicación por difenhidramina / Use of lipid emulsions in the successful treatment of a case of diphenhydramine poisoning / Uso de emulsões lipídicas no sucesso do tratamento de um caso de intoxicação por difenidramina

La difenhidramina tiene efectos antihistamínico anti-H1 específico y antimuscarínico que pueden ocasionar un desenlace fatal según la dosis total ingerida. Se reporta un caso de intoxicación por difenhidramina tratado de forma exitosa con emulsiones lipídicas a pesar de ingesta de dosis letal. Se presenta el caso de un paciente de 19 años que ingresó por intoxicación por difenhidramina a dosis de 25 mg/kg (1.5 g) después del tiempo de descontaminación, con toxidrome anticolinérgico, con neurotoxicidad, cardiotoxicidad (QRS y QT prolongados) y sin respuesta al enfoque inicial, se iniciaron emulsiones lipídicas y, a su vez, se logró alta temprana por evolución clínica favorable y resolución de la prolongación del intervalo QTc y del cuadro anticolinérgico. La emulsión lipídica es una opción terapéutica para disminuir la morbimortalidad y la estancia hospitalaria por contrarrestar la cardiotoxicidad y neurotoxicidad producidas por moléculas lipofílicas como la difenhidramina.

Diphenhydramine has specific anti-H1 antihistamine and antimuscarinic effects that can be fatal depending on the total dose ingested. A case of diphenhydramine poisoning successfully treated with lipid emulsions despite ingesting a lethal dose is presented. We present the case of a 19-year-old patient who was admitted for diphenhydramine intoxication at a dose of 25 mg/kg (1.5 g) after the decontamination time, with anticholinergic toxidrome, with neurotoxicity, cardiotoxicity (prolonged QRS and QT) and without response to initial approach. Lipid emulsions were started and, in turn, early discharge was achieved due to favorable clinical evolution and resolution of the prolongation of the QTc interval and the anticholinergic symptoms. Lipid emulsion is a therapeutic option to reduce morbidity and mortality and hospital stay by counteracting cardiotoxicity and neurotoxicity produced by lipophilic molecules such as diphenhydramine.

A difenidramina tem efeitos anti-histamínicos e antimuscarínicos anti-H1 específicos que podem ser fatais dependendo da dose total ingerida. Relata-se um caso de intoxicação por difenidramina tratada com sucesso com emulsões lipídicas apesar da ingestão de uma dose letal. Apresentamos o caso de uma paciente de 19 anos que foi internada por intoxicação por difenidramina na dose de 25 mg/kg (1,5 g) após o tempo de des-contaminação, com toxina anticolinérgica, neurotoxicidade, cardiotoxicidade (QS e QT prolongados) e sem resposta na abordagem inicial, iniciaram-se emulsões lipídicas e, por sua vez, obteve-se alta precoce devido à evolução clínica favorável e resolução do prolongamento do intervalo QTc e dos sintomas anticolinérgicos. A emulsão lipídica é uma opção terapêutica para reduzir a morbimortalidade e o tempo de internação por neutralizar a cardiotoxicidade e a neurotoxicidade produzidas por moléculas lipofílicas como a difenidramina.

Nedocromil sodium and diphenhydramine HCl ameliorate exercise-induced arterial hypoxemia in highly trained athletes.

INTRODUCTION: Exercise-induced arterial hypoxemia (EIAH) has been observed in highly trained endurance athletes during near maximal exercise, which may be influenced by a histamine-mediated inflammatory response at the pulmonary capillary-alveolar membrane. In order to test this hypothesis, we examined whether the mast cell stabilizer nedocromil sodium (NS) and H1 -receptor antagonist diphenhydramine HCL (DH) would ameliorate EIAH and mitigate the drop in arterial oxyhemoglobin saturation (Sa O2 ) during intensive exercise. METHODS: Seven highly trained male cross country runners (age, 21 ± 2 years; V̇O2max , 74.7 ± 3.5 ml·kg-1 ·min-1 ) participated in the study. All subjects completed a maximal exercise treadmill test to exhaustion, followed by three 5-min constant-load exercise bouts at 70%, 80%, and 90% V̇O2max . Prior to testing, subjects received either placebo (PL), NS, or DH. RESULTS: Compared to PL, there was a significant treatment effect on Sa O2 (p < 0.001) for both NS and DH during both constant-load exercise and at V̇O2max . Post hoc tests revealed Sa O2  values, compared to PL, were significantly higher at V̇O2max and during DH trials and higher with NS at constant-load intensities except at 70% (p = 0.13). CONCLUSION: The findings provide further evidence that histamine contributes directly or indirectly to the development of EIAH during intense exercise in highly trained athletes.

A randomized double-blind feasibility study comparing cetirizine and diphenhydramine in the prevention of paclitaxel-associated infusion-related reactions: the PREMED-F1 study.

PURPOSE: Cetirizine is a less sedative alternative to diphenhydramine for the prevention of infusion-related reactions (IRR) to paclitaxel. However, its use remains controversial. In this study, we assessed feasibility for a future definitive non-inferiority trial comparing cetirizine to diphenhydramine as premedication to prevent paclitaxel-related IRR. METHODS: This was a single-center randomized prospective feasibility study. Participants were paclitaxel-naive cancer patients scheduled to start paclitaxel chemotherapy. They were randomly assigned to receive either intravenous diphenhydramine 50 mg + oral placebo (control) or intravenous placebo + oral cetirizine 10 mg (intervention) for their first two paclitaxel treatments. The percentage of eligible patients completing a first paclitaxel treatment and the recruitment rate were assessed (feasibility outcomes). Drowsiness was measured at baseline and at selected time points using the Stanford Sleepiness Scale (SSS) (safety outcome). IRR events were also documented (efficacy outcome). RESULTS: Among 37 eligible patients, 27 were recruited and randomized (control 13; intervention 14) and 25 completed the study. The recruitment rate was 4.8 participants/month, meeting the primary feasibility target. Drowsiness was the main adverse effect associated with the premedication. The increase in drowsiness compared to baseline (ΔSSS) was greater in the diphenhydramine group compared to the cetirizine group (median ΔSSS 2 (IQR 3.25) vs median ΔSSS 0 (IQR 1), p < 0.01) when measured one hour after the premedication administration. One participant had an IRR and no unexpected serious adverse event occurred. CONCLUSION: The trial methods were feasible in terms of recruitment, retention, and safety. Cetirizine was significantly less sedating than diphenhydramine. IRR were infrequent and a larger trial is warranted to confirm non-inferiority for IRR prevention. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04237090 (22.01.2020).

The Role of Cetirizine in the Changing Landscape of IV Antihistamines: A Narrative Review.

Since 1955, the only available H1 antihistamines for intravenous administration have been first-generation formulations and, of those, only intravenously administered (IV) diphenhydramine is still approved in the USA. Orally administered cetirizine hydrochloride, a second-generation H1 antihistamine, has been safely used over-the-counter for many years. In 2019, IV cetirizine was approved for the treatment of acute urticaria. In light of this approval, this narrative review discusses the changing landscape of IV antihistamines for the treatment of histamine-mediated conditions. Specifically, IV antihistamines will be discussed as a treatment option for acute urticaria and angioedema, as premedication to prevent infusion reactions related to anticancer agents and other biologics, and as an adjunct treatment for anaphylaxis and other allergic reactions. Before the development of IV cetirizine, randomized controlled trials of IV antihistamines for these indications were lacking. Three randomized controlled trials have been conducted with IV cetirizine versus IV diphenhydramine in the ambulatory care setting. A phase 3 trial of IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 262 adults who presented to the urgent care/emergency department with acute urticaria requiring antihistamines. For the primary efficacy endpoint, defined as change from baseline in a 2-h patient-rated pruritus score, non-inferiority of IV cetirizine to IV diphenhydramine was demonstrated (score - 1.6 vs - 1.5, respectively; 95% CI - 0.1, 0.3). Compared with IV diphenhydramine, IV cetirizine demonstrated fewer adverse effects including less sedation, a significantly shorter length of stay in the treatment center, and fewer returns to the treatment center at 24 and 48 h. Similar findings were demonstrated in another phase 2 acute urticaria trial and in a phase 2 trial assessing IV cetirizine for pretreatment for infusion reactions in the oncology/immunology setting. IV cetirizine is associated with similar patient outcomes, fewer adverse effects, and increased treatment center efficiency than IV diphenhydramine.

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

BACKGROUND: 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. METHODS: Eighty-five patients undergoing maxillofacial surgery were randomized into two groups. The diphenhydramine group (Group D, n = 40) received diphenhydramine premedication 0.5 mg/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 0.1 mg/kg morphine sulfate slowly intravenously within 5 min. Continuous infusion of remifentanil 0.2 µg/kg/h and inhalation of isoflurane was maintained during the anesthesia period. Paracetamol 1 g was infused 15 min before extubation. We evaluated the incidence of agitation during the extubation period after general anesthesia, hemodynamic parameters, and recovery characteristics during the postoperative period. RESULTS: 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 (7.7 min in Group D vs. 6.8 min 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. CONCLUSIONS: Preemptive administration of diphenhydramine provided smooth emergence from anesthesia. It also improved the quality of recovery after maxillofacial surgery. TRIAL REGISTRATION NUMBER: This study was registered at http://irct.ir (registration number IRCT20130304012695N3).

UHPLC-MS/MS Method for Quantifying Fangchinoline, Tetrandrine and Calycosin-7-O-ß-D-Glucoside of Fangji Huangqi Decoction in Rat Plasma and Its Application to a Pharmacokinetic Study.

Fangji Huangqi Decoction is composed of Stephaniae Tetrandrae Radix, Astragli Radix, Atractylodis Macrocephalae Rhizoma and Glycyrrhizae Radix Et Rhizoma. It is a classic traditional Chinese medicine formula for the treatment of chronic glomerulonephritis in China. However, its pharmacokinetic characteristics in vivo are still unclear. In this study, a method for quantifying fangchinoline, tetrandrine and calycosin-7-O-ß-D-glucoside, the main active constituents of Fangji Huangqi Decoction, in rat plasma by using ultrahigh-performance liquid chromatography-tandem mass spectrometry technique was developed. Plasma samples were processed with a deproteinization procedure using acetonitrile, followed by chromatographic separation on a Shim-pack XR-ODS C18 column using gradient elution of 0.1% aqueous formic acid and acetonitrile at 0.4 mL/min. The analytes and internal standard, diphenhydramine hydrochloride, were detected using positive electrospray ionization in multiple reactions monitoring mode. The optimized mass transition ion-pairs (m/z) were 609.3/367.3 for fangchinoline, 623.3/174.3 for tetrandrine, 447.2/285.1 for calycosin-7-O-ß-D-glucoside and 256.2/167.1 for diphenhydramine hydrochloride, respectively. The developed method was validated for intraday and interday precision and accuracy whose values fell in the acceptable limits. Recovery efficiency of all the analytes was found to be >90.5%. Matrix effect was found to be negligible. Stability results showed that the analytes were stable under all conditions. The validated method was successfully used for studying the pharmacokinetics of the three compounds in rat plasma after oral administration of Fangji Huangqi Decoction.

Prophylactic Administration of Diphenhydramine/Acetaminophen and Ondansetron Reduced Postoperative Nausea and Vomiting and Pain Following Laparoscopic Sleeve Gastrectomy: a Randomized Controlled Trial.

PURPOSE: Postoperative nausea and vomiting (PONV) and pain following bariatric surgery are problematic and affect the outcome of patients. Intraoperative multimodal antiemetic prophylaxis is essential to improve postoperative outcomes. This study investigated the effect of adding diphenhydramine to acetaminophen and ondansetron in reducing postoperative nausea and vomiting and pain following laparoscopic sleeve gastrectomy (LSG). MATERIALS AND METHODS: Eighty-two patients scheduled for LSG were assigned to receive a single preinduction dose of diphenhydramine 0.4 mg/kg VI (D group) in addition to acetaminophen 1g and ondansetron 4 mg IV at the end of surgery and just acetaminophen 1 g and ondansetron 4 mg IV (C group) in a randomized, double-blind trial. PONV was assessed in recovery and 24 hours after surgery in the ward. Postoperative pain, analgesic requirements, and patients' level of sedation were also assessed. RESULTS: The PONV rates in the recovery of the D group and the C group were 30% and 56% (P = .001). It also had a more significant reduction in the D group than in the C group in the first 24 h after surgery (40% vs. 66%). The severity of pain score and level of sedation and analgesic requirements was significantly reduced in this period in the D group. CONCLUSION: Prophylactic diphenhydramine 0.4 mg/kg at the induction of general anesthesia in combination with acetaminophen 1 g and ondansetron 4 mg at the end of surgery reduced the incidence of PONV and postoperative severity of pain in laparoscopic sleeve gastrectomy.

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.

Diphenhydramine may be a preventive medicine against cisplatin-induced kidney toxicity.

Cisplatin is widely used as an anti-tumor drug for the treatment of solid tumors. Unfortunately, it causes kidney toxicity as a critical side effect, limiting its use, given that no preventive drug against cisplatin-induced kidney toxicity is currently available. Here, based on a repositioning analysis of the Food and Drug Administration Adverse Events Reporting System, we found that a previously developed drug, diphenhydramine, may provide a novel treatment for cisplatin-induced kidney toxicity. To confirm this, the actual efficacy of diphenhydramine was evaluated in in vitro and in vivo experiments. Diphenhydramine inhibited cisplatin-induced cell death in kidney proximal tubular cells. Mice administered cisplatin developed kidney injury with significant dysfunction (mean plasma creatinine: 0.43 vs 0.15 mg/dl) and showed augmented oxidative stress, increased apoptosis, elevated inflammatory cytokines, and MAPKs activation. However, most of these symptoms were suppressed by treatment with diphenhydramine. Furthermore, the concentration of cisplatin in the kidney was significantly attenuated in diphenhydramine-treated mice (mean platinum content: 70.0 vs 53.4 µg/g dry kidney weight). Importantly, diphenhydramine did not influence or interfere with the anti-tumor effect of cisplatin in any of the in vitro or in vivo experiments. In a selected cohort of 98 1:1 matched patients from a retrospective database of 1467 patients showed that patients with malignant cancer who had used diphenhydramine before cisplatin treatment exhibited significantly less acute kidney injury compared to ones who did not (6.1 % vs 22.4 %, respectively). Thus, diphenhydramine demonstrated efficacy as a novel preventive medicine against cisplatin-induced kidney toxicity.