Use Of Premedication Research Articles

Contrast Medium Hypersensitivity: A Large Italian Study with Long-Term Follow-Up.

Hypersensitivity reactions (HRs) to contrast media (CM) are a major problem. We compared differences of HRs to iodinated contrast media (ICM) versus gadolinium-based contrast media (GBCM), collecting data on prevalence, type, latency and severity. Secondly, the predisposition to perform new contrast tests, use of premedication and possible appearance of new reactions were explored in a long-term follow-up of 5 years. Clinical data, comorbidities, skin test (ST) results, re-exposure to CM procedures with any new reactions, premedication and CM used were collected. In a retrospective single-center study, 350 patients with mild to moderate HRs were enrolled. Asthma, food allergy, non-allergic drug hypersensitivity and neurologic disease were significantly more frequent in patients with HRs to GBCM compared to the high evidence of cardiovascular disease and history of cancer in patients with HRs to ICM. A marked delay in performing STs was reported by patients with negative results (66 months, p < 0.01). Iomeprol, iopamidol and gadobenic acid were the culprit CM most involved in HRs in patients with positive STs. During follow-up, 7.1% of responders reported new HRs to CM despite negative STs, premedication and infusion of alternative CM in most cases.

Evaluating Iodixanol as a safe alternative in iodinated contrast hypersensitivity reactions

Prevalence of hypersensitivity reactions to iodinated contrast media is around 0.5-3%. According to European and American practice guidelines, allergy tests should include skin tests followed by drug provocation test (DPT) with a non-related radiocontrast media (RCM) with or without premedication use.

Prospective cohort study to evaluate premedication with simethicone and n-acetilcysteine for upper diagnostic gastrointestinal endoscopy.

The use of premedication for upper gastrointestinal endoscopy (UGE) is not widely established in western countries. The primary aim of the study was to compare gastric visibility according to the total visibility score (TVS). The secondary aim was to assess complications, diagnostic yield, endoscopic procedure time, sedation dose and patient satisfaction. A single center prospective cohort study was performed of consecutive adults undergoing an UGE in the afternoon working shift. After completing enrolment in the control group, patients were administered 200 mg simethicone and 500 mg N-acetylcysteine diluted in 100 ml of water >15 minutes before the procedure. All procedures were recorded and a single, blinded endoscopist evaluated the TVS after recruitment of both cohorts. Patient satisfaction was evaluated using the Spanish translation of the American Society of Gastrointestinal Endoscopy satisfaction questionnaire. 205 patients were included in the study, 103 females (50.2%) with a median age of 54.8-years (IQR: 41.2-65.2). 104 were enrolled to the control group and 101 to the intervention group. Patients receiving premedication presented a higher rate of adequate (74.3% vs 45.2; difference 95% CI: 16,3-41,9%, p<0.001) and excellent gastric visibility (23.8% vs 7.7%; difference 95% CI: 6,3-25,8%, p=0.002). Propofol dose was similar, although the median procedure time was lower in the group of no intervention [5 (IQR: 4-7) vs 6 minutes (IQR: 5-7); p=0.03]. Procedure related adverse events were similar, except that patient without premedication experienced more nausea episodes. Major and minor endoscopic findings and the satisfaction questionnaire showed no differences between both groups. Patients receiving premedication with simethicone and N-acetylcysteine had a better gastric visibility score, without any increase in adverse events or affecting the patients' satisfaction.

Incidence and risk factors of late adverse reactions to low-osmolar contrast media: A prospective observational study of 10,540 exposures

PurposeTo evaluate the incidence and risk factors of late adverse reactions (ARs) to non-ionic low-osmolar contrast media (LOCM). MethodsThe occurrence of late AR was monitored on day 1 and from day 7 to day 28 in all patients who received enhanced computed tomography using LOCM during a 5-week study period in a single tertiary hospital. Patients who experienced late AR were followed up for three years. ResultsAmong the total 10,540 LOCM exposures, 315 ARs (3.0%) were reported; acute ARs occurred in 108 LOCM exposures (1.0%) and late ARs occurred in 207 LOCM exposures (2.0%) (90.9% within one week, 9.1% developed afterwards by day 20). Previous history of drug allergy (odds ratio [OR] = 4.59; 95% confidence interval [CI] 2.17–9.71) and allergic diseases (OR = 2.54; 95% CI 1.32–4.91) were risk factors of late ARs to LOCM. Although the recurrence rate was lowered with premedication from 8.5% to 1.7% (8/94 vs. 3/178; p = 0.016), LOCM change did not make difference compared to reuse of the culprit LOCM (2/38 vs. 9/234; p = 0.655). In patients with a history of late AR to LOCM, the risk of recurrent reactions decreased with longer time intervals between exposures (OR = 0.86; 95% CI: 0.77–0.97; p = 0.025) and with the use of antihistamine premedication (OR = 0.27; 95% CI: 0.06–0.99; p = 0.049). ConclusionsLate ARs to LOCM occurred mostly within one week. The use of premedication may be helpful in reducing the recurrence of late ARs.

Monoclonal Antibody Utilization Characteritics in Patients with Multiple Myeloma

Background: Monoclonal antibodies (MoAb) including daratumumab (Dara) and elotuzumab (Elo) are important additions to multiple myeloma (MM) therapeutics and have become cornerstones of patients with relapsed and/or refractory disease (RRMM). While large clinical trial data define their efficacy and safety, real-world experience to help understand their true utilization and serve as guidelines for community practice are lacking.Methods: Data on the utilization of Dara and Elo for treatment of MM including patient and disease characteristics, infusion attributes, supportive medication use and adverse event profile were collected and analyzed using descriptive statistics. Baseline laboratory data including median absolute lymphocyte count (ALC), eosinophil count (AEC), neutrophil count (ANC) and immunoglobulin level (Ig) were documented and their correlation with infusion-related reactions (IRRs) was explored using Wilcoxon rank sum test.Results: Ninety-one consecutive patients with MM treated using Dara (n=78) or Elo (n=13) not on clinical trials between 1/1/16 and 12/31/16 at Mayo Clinic in Florida (MCF; n=30) or Arizona (MCA; n=61) were included. A total of 1036 infusions of Dara (Median: 12 per patient; Range: 1-38) and 210 of Elo (Median: 18 per patient; Range: 3-29) were administered over 12 months. Study cohort included 56 males (61.5%) with median age 63 years (range: 37-81) and majority (83.5%) of Caucasian race. Treatment regimes of MoAb alone or with immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) are shown in Figure 1. Prior lines of therapy were >3 in 52.7%, 3 in 13.2%, 2 in 19.8%,1 in 12.1% and in 1 case each Dara and Elo were given in first line of therapy. Majority of patients who received Dara (60.3%) had >3 prior lines of therapy while majority who received Elo (53.8%) had 1 prior line of therapy for MM. Pre-treatment blood sample for type/screen was sent in 67% patients. Any grade hematologic (heme) adverse events (AE) were seen in 66 (84.6%) patients with Dara and 6 (46.2%) patients with Elo, while non-heme AEs were seen in 64 (82.1%) patients with Dara and 11 (84.6%) patients with Elo. Actual MoAb administration took an average 2 hours lesser (Range: -3 to +6 hours for Dara and -1 to +5 hours for Elo) than scheduled with median 2 hours lesser for both the drugs. In 2 cases first Dara infusion was given in divided dose over 2 days. Most common premedications prior to first MoAb infusion included acetaminophen (90.1% cases), diphenhydramine (86.8% cases) and methylprednisone (78% cases) with dexamethasone, famotidine, prochlorperazine and ondansetron used less frequently. Number of patients without any premedications use changed from 9.9% before infusion 1 to 94.5% before infusion 29 of any MoAb, showing a sharp decrease in the use of premedications in subsequent dose infusions of MoAbs. IRRs were seen in 39 (42.9%) patients with first MoAb infusion with respiratory IRRs (bronchospasm, cough, dyspnea, nasal congestion, throat irritation, wheezing) seen in 35 (38.5%) and non-respiratory IRRs (chills, nausea, hypertension, tachycardia, pruritus, bradycardia, emesis) in 16 (17.6%) patients. No patients had any higher than grade 2 IRRs. Majority of the IRRs (91.3%) were observed during the first MoAb infusion, none of the patient's required discontinuation of MoAb treatment as a result of IRRs, with a significant decrease in IRR incidence during second (3.3%) and subsequent (5.4%) infusions. In 10 cases (9 for Dara and 1 for Elo) premedication regimen was modified after first infusion. MoAb AEs seen in ≥10% cases across various regimens included neutropenia (51.6%), lymphopenia (42.9%), thrombocytopenia (33%), anemia (18.7%), fatigue (40.7%), diarrhea (22%), pneumonia (22%), cough (18.7%), fever (18.7%) and nausea (12.1%). Median baseline labs included ALC 0.95 K/mm3, ANC 2.22 K/mm3 and AEC 0.07 K/mm3. There was no association seen between median baseline ALC, ANC or AEC and the risk of any IRRs, respiratory or non-respiratory.Conclusions: We present a comprehensive analysis of real-world experience regarding the utilization of novel MoAb agents for the treatment of MM. Although the role of MoAbs in MM therapeutics is evolving, these data help understand their true utilization and identify how resources may be best employed to optimize their benefit for patients. [Display omitted] DisclosuresAilawadhi:Novartis: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Pharmacyclics: Research Funding; Amgen: Consultancy, Honoraria. Sher:LAM Therapeutics, Inc: Research Funding. Fonseca:Bayer: Consultancy; Takeda: Consultancy; Jansen: Consultancy; Celgene Corporation: Consultancy, Research Funding; AMGEN: Consultancy; Bristol-Myers Squibb: Consultancy; Mayo Clinic & Dr Fonseca: Patents & Royalties: Prognostication of myeloma via FISH, ~$2000/year; Merck: Consultancy; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy; Novartis: Consultancy; Pharmacyclics: Consultancy.

Brentuximab Vedotin Plus Bendamustine Is an Effective Salvage Regimen for Pediatric Patients with Relapsed Hodgkin Lymphoma

Background :Pediatric patients with relapsed/refractory Hodgkin Lymphoma have superior outcomes when achieving a complete remission prior to autologous stem cell transplant (ASCT). Optimal salvage regimens need to be identified as current approaches result in complete responses (CR) in approximately 25-35% of patients. The combination of brentuximab vedotin and bendamustine is highly active in adult patients with relapsed/refractory Hodgkin Lymphoma, but has not been evaluated in the pediatric population. We report our preliminary experience regarding the safety and efficacy of brentuximab vedotin and bendamustine prior to stem cell transplant (SCT) in pediatric patients treated for relapsed Hodgkin lymphoma at a single center.Methods:We performed a retrospective review of pediatric patients with relapsed Hodgkin lymphoma treated with brentuximab vedotin and bendamustine between April 2016 to July 2017. Patients received an infusion of 1.8mg/kg of brentuximab vedotin on Day 1 with bendamustine 90mg/m2 on Days 1 and 2 of 3-week cycles. Response assessment was performed and repeated following 2-3 cycles of therapy. Patients went on to SCT after achieving a CR or best response at the discretion of the treating physicians. Patients resumed post-transplant treatment with brentuximab vedotin as monotherapy for up to 16 doses.Results:Five patients (1 female, 4 males) with a median age of 16.5 years at the time of relapse (range, 12.2 -17.9 years) were treated with the combination of brentuximab/bendamustine. Four patients were in first relapse and 1 was treated in second relapse nine months following a prior ASCT. Patients received a median of 5 cycles of therapy (range 2-5 cycles), with 2 patients receiving an additional cycle of brentuximab monotherapy prior to proceeding to SCT. The main toxicity observed was infusion-related reactions, with 2 patients experiencing anaphylaxis. These individuals were able to continue planned therapy following desensitization against brentuximab. All patients were in complete remission by PET prior to SCT. Four patients underwent successful stem cell mobilization and collection. The individual treated following second relapse received an allogeneic transplant from a matched unrelated donor. All patients are alive with no evidence of disease a median of 11.3 months since beginning salvage therapy (range 1.2-15 months). Four patients are a median of 6.5 months (range 4-11 months) post-SCT and continue on brentuximab monotherapy, with 1 individual currently awaiting ASCT.Conclusions :Combination therapy with brentuximab vedotin and bendamustine was highly active in pediatric patients with relapsed Hodgkin lymphoma and would compare favorably with currently accepted salvage regimens. Incidence of infusion-related reactions can be minimized through the use of adequate premedication. These results support further evaluation of this regimen in the context of a multicenter prospective clinical trial. DisclosuresCurran:Novartis: Consultancy; Juno Therapeutics: Research Funding. Kernan:Gentium: Other: NAK received grants from Gentium during the conduct of the study, and her research was supported by The National Cancer Institute of the National Institutes of Health under award number P30 CA008748; the content is solely the responsibility of the author .

Use of Premedication Prior to Asparaginase (ASNase) Administration in Pediatric Acute Lymphoblastic Leukemia (ALL): Effect on Treatment Completion Rate

BackgroundIn pediatric patients with ALL, completion of ASNase treatment has been shown to improve survival (Silverman LB et al. Blood . 2001;97(5):1211-1218). Premedication has been used to reduce infusion and hypersensitivity reactions associated with ASNase therapy; however, premedication may mask the appearance of systemic hypersensitivity reactions, which may be associated with the development of neutralizing antibodies and reduced ASNase activity (Woods D et al. J Pediatr Oncol Nurs . 2017. doi:10.1177/1043454217713455). In the US, 2 formulations of asparaginase are available, a PEGylated form (PEG) of Escherichia coli- derived ASNaseand an immunologically distinct Erwinia chrysanthemi- derived form (ERW). Reported here are results of a physicians' survey conducted via market research to assess the effects of premedication on completion of ASNase treatment.MethodsAn online market research survey of US hematology/oncology physicians collected information on their treatment of pediatric ALL patients since the beginning of 2014. A patient chart audit was also included. Recruited physicians were required to have 2-35 years in practice, ≥75% of time in direct patient care with 80% compliance with treatment using Children's Oncology Group, Dana-Farber, St. Jude, or other pediatric ALL protocols. Patients (aged 1-21 years) were required to be personally managed by a physician, currently receiving or had received treatment for ALL. Physician practice setting affiliation (academic vs community), ASNase use, premedication (premed vs no-premed) use, ASNase-therapy interruption due to complications (physician-assessed hypersensitivity reaction [HSR] or other toxicity) and subsequent treatment decisions (PEG rechallenge, switch to ERW), and rates of therapy completion were also collected. Data collected were descriptive in nature and no inferential statistical tests were performed.ResultsEighty-five hematologists/oncologists (44% academic, 56% community) provided audited charts for 323 patients (median age, 14 years; 62% classified as high or very-high risk). For the 231 patients receiving PEG as initial ASNase therapy, premedication for the first and/or subsequent doses was used in 151 patients (65%). Premedications included antihistamines (60%), acetaminophen (59%), antiemetics (48%), and steroids (39%). Among the premed patients (n=151), 15 patients had ASNase treatment interrupted, 12 (80%) due to physician-assessed HSR. Among the no-premed patients (n=80), 13 patients had treatment interrupted, 10 (77%) due to physician-assessed HSR (Figure 1). These rates were higher than those for discontinuation due to toxicities other than HSR (3/15, 20% vs 3/13, 23%). For the premed patients with HSR, 5 were switched to ERW, and 7 were rechallenged with PEG. For the no-premed group, all 10 patients were switched to ERW. In patients with HSR, overall completion rates at time of audit were lower in the premed group (58%; 7/12) than in the no-premed group (100%; 10/10; 1 patient in each group was still on therapy at time of audit; Figure 2).ConclusionsIn this chart audit, the majority of pediatric ALL patients treated with PEG as initial ASNase therapy received premedication (65%). Hypersensitivity-like reaction was the most common physician-reported reason for ASNase treatment interruption, even in premedicated patients (80% of treatment interruptions). Patients without premedication had a higher rate of ASNase treatment completion than those who were premedicated. These results should be interpreted with caution given the retrospective nature of this chart audit, the subjective nature of HSR determination, and the small patient numbers.Support: Jazz Pharmaceuticals. [Display omitted] DisclosuresBernard:Jazz Pharmaceuticals: Employment. Rustay:Jazz Pharmaceuticals: Employment, Other: stock options. Mamedov:Jazz Pharmaceuticals: Employment, Other: stock options.

Incidence of Bradycardia and the Use of Atropine in Pediatric Rapid Sequence Intubation in the Emergency Department.

Bradycardia during rapid sequence intubation (RSI) is an uncommon but serious adverse effect encountered in pediatric intubations. Atropine has historically been used in the pediatric population as RSI premedication to prevent bradycardia, especially when using succinylcholine as an induction agent. The objective of this analysis was to identify the incidence of bradycardia with or without atropine use. This single-center, retrospective, observational case series reviewed pediatric patients up to 18 years old requiring intubation from January 1, 2015, to December 31, 2018. Bradycardia was determined by analyzing heart rates associated with time during and up to 5 minutes after intubation. A total of 62 patients were included. Three (4.8%) patients experienced a bradycardic event during intubation. A total of 15 (24.2%) patients received atropine for pretreatment of RSI. Incidence of bradycardia was similar between those who received atropine and those who did not. An increasing trend in atropine use was shown throughout the assessment period, yet only 18 (29%) patients met criteria for atropine pretreatment based on the 2015 Pediatric Advanced Life Support guideline recommendations for RSI. Bradycardia incidence was low in pediatric patients undergoing RSI in our emergency department. Use of atropine or succinylcholine did not affect the incidence of bradycardia during pediatric intubation over this study period. Our results show a low incidence of bradycardia and support the 2015 Pediatric Advanced Life Support Guideline recommendation of limiting the use of atropine premedication in pediatric intubations.

Anaesthesia for radiotherapy in paediatric oncology-a retrospective observational study in an Asian population.

Immobilisation in radiotherapy treatment is especially important as many paediatric tumours are located near critical organs. Although the external beam radiotherapy treatment process itself is painless, the immobilization devices used may cause anxiety and discomfort in children who are too young to understand and co-operate. Hence, anaesthesia or sedation is unavoidable in such cases. This descriptive study aims to evaluate the demographics, methods and outcomes of paediatric radiotherapy patients in our Asian context. This is a single-institution, retrospective observational study in a tertiary hospital with more than a decade of experience in paediatric radiotherapy. Data collected include age, gender, race, ASA status, oncology diagnosis, site of radiotherapy, position of patient during procedure, need for sedation or anaesthesia, anaesthetic drugs used, airway devices, use of premedications, use of antiemetics, and incidence and type of complications. We also analysed the association between various factors (e.g., age, radiotherapy treatment site) and usage of anaesthesia. Statistical analysis was carried out using a multivariable model. Between January 2006 and December 2017, 434 paediatric patients underwent radiotherapy, with a total of 10,357 discrete radiotherapy sessions. In 1,276 radiotherapy sessions (11.8%) either general anaesthesia or sedation was required. The need for anaesthesia was highly age-dependent-all patients under 3 years of age required anaesthesia, whereas anaesthesia was rarely needed in patients above 7 years of age. Our institution had a higher prevalence of inhalational agent usage as opposed to intravenous agent usage. Complication rate was relatively low. This is the first retrospective review performed in our country on paediatric patients receiving anaesthesia during radiotherapy, evaluating patients' demographic data, and type of anaesthesia and radiotherapy techniques used. We found that patients' requirement for anaesthesia decreases in an age-dependent fashion, in line with existing literature. Our reported complication rate during anaesthesia sessions was low, testament to the high standards and safety of our techniques.

Characterization of cytokine release syndrome (CRS) following treatment with tebentafusp in patients (pts) with previously treated (2L+) metastatic uveal melanoma (mUM).

9531 Background: Cytokine-mediated adverse events (AEs) are commonly reported in pts treated with T cell engaging therapies. Tebentafusp (tebe), a bispecific consisting of an affinity-enhanced T cell receptor fused to an anti-CD3 effector that can redirect T cells to target gp100+ cells, has shown an overall survival benefit for pts with untreated mUM in a Ph3 trial (NCT03070392). Here we reviewed the incidence, kinetics, and outcome of CRS in tebe-treated pts on the IMCgp100-102 trial of 2L+ pts with mUM (NCT02570308). Methods: 127 HLA-A*02:01+ 2L+ mUM pts were treated with tebe at the RP2D of 68mcg following intra-patient dose escalation of 20 mcg dose 1 and 30 mcg dose 2. Pts were monitored overnight to allow management of hypotension and other cytokine-related AEs. Because the rate of severe CRS was low in Ph1, prophylactic corticosteroids, antihistamines or acetaminophen were not mandated. CRS was evaluated post-hoc according to ASTCT Consensus Grading criteria [1]. Circulating cytokines in serum were measured before and at 8hr and 12-24hr after dosing for the 1st, 3rd and 4th doses (n=105). This analysis was conducted on the primary analysis snapshot dated 04Jun20. Results: The most frequent treatment-related AEs that were likely cytokine-mediated included fever (80%), chills (64%), nausea (59%), hypotension (41%) and hypoxia (4%). In a post-hoc review using ASTCT criteria, 86% of pts (n=109) had any grade CRS. The majority of these 109 pts had either grade (G) 1 (n=42; 33%) or G2 (n=62; 49%), with few G3 (n=4; 3.1%), one G4 (0.8%), and no deaths. Onset of CRS began within 24 hours of administration and G≥2 hypotension or hypoxia typically resolved within 2 days of onset. Most CRS events occurred after the first 3 doses with a marked reduction in the frequency and severity of CRS thereafter; G3-4 CRS was limited to first two doses. Only 2 pts discontinued tebe due to CRS (1 G3 and 1 G4). Treatment of G≥2 CRS included iv fluids (n=45), iv steroids (n=18), oxygen (n=8), and vasopressor use (n=2). No pts received tocilizumab. Tebe induced a transient increase in peripheral cytokines, including IFNγ, IL-10, IL-6 and TNFα, within hours of tebe dosing, which were several fold higher in pts with CRS compared to pts without CRS. Higher levels of TNFα trended with severity of CRS. Conclusions: CRS, a common AE observed with all T cell engaging therapies, was frequently observed within 24 hours of initial tebe treatment. Most CRS events were mild or moderate in severity even without the use of prophylactic premedications, were reversible with standard management strategies, decreased in frequency and severity with subsequent doses, and rarely led to treatment discontinuation. Pts with CRS tended to have greater increases in serum cytokines, consistent with tebe’s proposed mechanism of action. [1] Lee, DW et al. Biol Blood Marrow Transplant 2019. Clinical trial information: NCT02570308.

Premedication prior to PEG-asparaginase is cost-effective in pediatric patients with acute lymphoblastic leukemia.

PEG-asparaginase is critical in pediatric acute lymphoblastic leukemia (ALL) therapy but is highly immunogenic. Severe allergic reactions lead to substitution of further PEG-asparaginase with Erwinia. Erwinia is associated with more frequent dosing, increased expense, and limited availability. Premedication may reduce rates of allergic reactions. This Markov model evaluated the cost-effectiveness of three strategies: premedication plus therapeutic drug monitoring (TDM), TDM alone, and no premedication or TDM. We modeled two scenarios: a standard-risk (SR) B-ALL patient receiving two asparaginase doses and a high-risk (HR) patient receiving seven asparaginase doses. The model incorporated costs of asparaginase, premedication, TDM and clinic visits, and lost parental wages associated with each additional Erwinia dose. We incorporated a five-year time horizon with a societal perspective. Outcomes were Erwinia substitutions avoided and differences in quality-adjusted life years (QALYs). Probabilistic and one-way sensitivity analyses evaluated model uncertainty. In both scenarios, premedication was the least costly strategy. In SR and HR scenarios, premedication with monitoring resulted in 8% and 7% fewer changes toErwiniacompared with monitoring alone and 3% and 2% fewer changes compared with no premedication/monitoring, respectively. Premedication resulted in the most QALYs gained in the SR patients. Individual variation of model inputs did not change premedication/monitoring favorability for either scenario. In probabilistic sensitivity analyses, premedication/monitoring was favored in >87% of iterations in both scenarios. Compared with other strategies, premedication use and asparaginase level monitoring in children with B-ALL is potentially cost-saving.

Premedication practices for neonatal tracheal intubation: Results from the EPIPPAIN 2 prospective cohort study and comparison with EPIPPAIN 1.

To describe the frequency and nature of premedication practices for neonatal tracheal intubation (TI) in 2011; to identify independent risk factors for the absence of premedication; to compare data with those from 2005 and to confront observed practices with current recommendations. Data concerning TI performed in neonates during the first 14 days of their admission to participating neonatal/pediatric intensive care units were prospectively collected at the bedside. This study was part of the Epidemiology of Procedural Pain in Neonates study (EPIPPAIN 2) conducted in 16 tertiary care units in the region of Paris, France, in 2011. Multivariate analysis was used to identify factors associated with premedication use and multilevel analysis to identify center effect. Results were compared with those of the EPIPPAIN 1 study, conducted in 2005 with a similar design, and to a current guidance for the clinician for this procedure. One hundred and twenty‐one intubations carried out in 121 patients were analyzed. The specific premedication rate was 47% and drugs used included mainly propofol (26%), sufentanil (24%), and ketamine (12%). Three factors were associated with the use of a specific premedication: nonemergent TI (Odds ratio (OR) [95% CI]: 5.3 [1.49‐20.80]), existence of a specific written protocol in the ward (OR [95% CI]:4.80 [2.12‐11.57]), and the absence of a nonspecific concurrent analgesia infusion before TI (OR [95% CI]: 3.41 [1.46‐8.45]). No center effect was observed. The specific premedication rate was lower than the 56% rate observed in 2005. The drugs used were more homogenous and consistent with the current recommendations than in 2005, especially in centers with a specific written protocol. Premedication use prior to neonatal TI was low, even for nonemergent procedures. Scientific consensus, implementation of international or national recommendations, and local written protocols are urgently needed to improve premedication practices for neonatal intubation.

Examining Variations in Surfactant Administration (ENVISION): A Neonatology Insights Pilot Project.

Variability in neonatal clinical practice is well recognized. Respiratory management involves interdisciplinary care and often is protocol driven. The most recent published guidelines for management of respiratory distress syndrome and surfactant administration were published in 2014 and may not reflect current clinical practice in the United States. The goal of this project was to better understand variability in surfactant administration through conduct of health care provider (HCP) interviews. Questions focused on known practice variations included: use of premedication, decisions to treat, technique of surfactant administration and use of guidelines. Data were analyzed for trends and results were communicated with participants. A total of 54 HCPs participated from June to September 2020. In almost all settings, neonatologists or nurse practitioners intubated the infant and respiratory therapists administered surfactant. The INSURE (INtubation-SURrfactant-Extubation) technique was practiced by 83% of participants. Premedication prior to intubation was used by 76% of HCPs. An FiO2 ≥ 30% was the most common threshold for surfactant administration (48%). In conclusion, clinical practice variations exist in respiratory management and surfactant administration and do not seem to be specific to NICU level or institution type. It is unknown what effects the variability in clinical practice might have on clinical outcomes.

A retrospective study of the safety and efficacy of low molecular weight iron dextran for children with iron deficiency anemia.

Iron deficiency anemia (IDA) affects millions of children worldwide. Oral iron replacement is effective but often poorly tolerated. Intravenous iron has been demonstrated to have utility in all ages, but pediatric use remains limited. Low molecular weight iron dextran (LMWID) has a dosing range capable of replacing iron deficits in a single infusion and has been evaluated in small pediatric cohorts, but additional safety and efficacy data are limited. Here, we evaluate the safety and efficacy of LMWID in association with an electronic medical record (EMR)-based effort to optimize dosing. A retrospective IRB-approved investigation of LMWID utilization at a tertiary pediatric hospital between January 1, 2016 and March 31, 2020 was undertaken to evaluate the therapeutic efficacy and frequency/severity of infusion-related adverse event (AE) in children and adolescents receiving LMWID. Patient demographics and LMWID dosing characteristics were collected, and primary outcome measures included laboratory response and the incidence/severity of any infusion-related events. The utilization of an EMR-based nomogram for LMWID dosing was also evaluated. A total of 254 infusions for 191 patients were included (ages 0.7-20.9years), most with IDA. LMWID replaced at least 75% of the estimated iron deficit in a single infusion for 76% of patients. The mean hemoglobin and ferritin increases were 2.1g/dl and >100ng/ml, respectively. Infusion-related AEs were rare, occurring in only 12/254 (4.7%) of infusions and 67% during the test dose; each rapidly resolved without long-term sequelae. No AEs occurred in those <10years of age. Premedication use markedly decreased with nomogram use without a change in AE rate. In a large institutional cohort, LMWID was well tolerated in children and adolescents, with most patients having their total iron deficits relieved in a single infusion. These data support expanded use of LMWID in the management of pediatric iron deficiency.

Midazolam Premedication Immediately Before Surgery Is Not Associated With Early Postoperative Delirium.

Postoperative delirium is common among older surgical patients and may be associated with anesthetic management during the perioperative period. The aim of this study is to assess whether intravenous midazolam, a short-acting benzodiazepine used frequently as premedication, increased the incidence of postoperative delirium. Analyses of existing data were conducted using a database created from 3 prospective studies in patients aged 65 years or older who underwent elective major noncardiac surgery. Postoperative delirium occurring on the first postoperative day was measured using the confusion assessment method. We assessed the association between the use or nonuse of premedication with midazolam and postoperative delirium using a χ2 test, using propensity scores to match up with 3 midazolam patients for each control patient who did not receive midazolam. A total of 1266 patients were included in this study. Intravenous midazolam was administered as premedication in 909 patients (72%), and 357 patients did not receive midazolam. Those who did and did not receive midazolam significantly differed in age, Charlson comorbidity scores, preoperative cognitive status, preoperative use of benzodiazepines, type of surgery, and year of surgery. Propensity score matching for these variables and American Society of Anesthesiology physical status scores resulted in propensity score-matched samples with 1-3 patients who used midazolam (N = 749) for each patient who did not receive midazolam (N = 357). After propensity score matching, all standardized differences in preoperative patient characteristics ranged from -0.07 to 0.06, indicating good balance on baseline variables between the 2 exposure groups. No association was found between premedication with midazolam and incident delirium on the morning of the first postoperative day in the matched dataset, with odds ratio (95% confidence interval) of 0.91 (0.65-1.29), P = .67. Premedication using midazolam was not associated with higher incidence of delirium on the first postoperative day in older patients undergoing major noncardiac surgery.

Does Premedication with Mucolytic Agents Improve Mucosal Visualization during Oesophagogastroduodenoscopy: A Systematic Review and Meta-Analysis.

Introduction Gastric Cancer (GC) is the fourth most common malignancy worldwide and the second leading cause of cancer-related mortality for both sexes. The gold standard for diagnosing GC is oesophagogastroduodenoscopy (OGD). Excess mucus on the gastric mucosa impairs the detection of early GC. Aim To synthesize available evidence of the effect of premedication with a mucolytic agent among adults undergoing elective nontherapeutic OGD, compared to placebo or other mucolytic agents, on mucosal visibility during OGD. Methods A systematic review was conducted. PubMed, EMBASE, CINAHL, Cochrane central register of controlled trials (CENTRAL), and Web of Science were searched for relevant studies. A random-effects meta-analysis was performed to determine the mean difference in total mucosal visibility score (TMVS) between the pooled mucolytic agents and control. Subgroup analyses were performed to determine the mean TMVS difference for simethicone versus control and the impact of different timings and doses of mucolytic premedication. Results 13 studies, involving 11,086 patients, including 6178 females (55.7%), with a mean age of 53.4 were identified and 6 of these were brought forward to meta-analysis. This revealed a mean difference of −2.69 (95% CI −3.5, −1.88) in total mucosal visibility scores (TMVS) between the pooled mucolytic agents and control. For simethicone, the mean difference was −2.68 (95% CI −4.94, −0.43). A simethicone dose of 133 mg was most effective with a mean difference of −4.22 (95% CI −5.11, −3.33). Assessing timing of administration across all mucolytic agents revealed a mean difference for the >20 minutes group of −3.68 (95% CI −4.77, −2.59). No adverse events were reported in any included trials. Conclusions Regular use of premedication with mucolytic agents prior to routine OGD is associated with improved TMVS with no reported adverse events.

Use of premedication with intravenous immune globulin in Kawasaki disease: A retrospective review.

Kawasaki disease (KD) is a significant febrile illness in children and is the leading cause of acquired pediatric heart disease in developed countries. Its recommended treatment is high-dose intravenous immune globulin (IVIG) plus aspirin. However, IVIG-related adverse events are seen frequently in this population. Premedication is commonly used to reduce this risk, but evidence supporting this practice is conflicting. Ultimately, practices vary among institutions and no standard guidelines regarding IVIG premedication currently exist. Electronic medical records for pediatric patients presenting to an academic, tertiary care medical center diagnosed with KD and who received at least one dose of IVIG were reviewed for: patient demographics, treatment characteristics, premedication use, adverse events, and coronary abnormalities at discharge. Descriptive statistics were used to evaluate study findings. Sixty-six patients receiving a total of 81 distinct IVIG administrations were evaluated. Most patients (64/66, 97%) were premedicated prior to infusion with 26% of patients (17/66) experiencing an IVIG-related adverse event, totaling 25 documented adverse events. The most common events included chills and vomiting. Overall, the average duration of hospitalization was 4.37days. Despite appropriate medication management, five patients (7.6%) developed coronary abnormalities. Practitioners demonstrated a widespread use of premedication for IVIG. However, 26% of patients still experienced an adverse event. While premedication was not shown to have an adverse impact on patient outcomes, it also did not demonstrate a notable reduction from a historic adverse event incidence.

Transfusion practice in Australia: an internet-based survey.

To describe small animal transfusion practices in Australia, including access to blood products and frequency of pre-transfusion compatibility testing and medication administration. An online survey was disseminated to target Australian veterinarians treating dogs and cats. Information collected included demographics, sources of blood products, blood storage, recipient compatibility testing and administration of medications pre-transfusion. Associations between the use of compatibility tests and premedications were assessed using the χ2 test. Significance was set at P < 0.05. A total of 199 Australian veterinarians were included; however, there was some attrition of respondents over the course of the survey. The majority of respondents were in general practice (n = 133/199). Access to fresh whole blood was commonly reported for dogs (n = 179/199) and cats (n = 131/198), whereas blood components were less commonly available (canine red blood cells [RBC], n = 52/199 and plasma, n = 157/199; feline RBC, n = 9/198 and plasma, n = 21/198). Most blood was sourced from the pets of owners affiliated with the veterinary clinic (n = 179/196). The respondents who did not blood type or crossmatch dogs were significantly more likely to use premedication than those who did these tests (both comparisons: P < 0.001). Likewise, the respondents who did not blood-type cats were significantly more likely to use premedication (P = 0.003); however, there was no association between crossmatching and using premedication in cats (P = 0.183). This is the first survey to describe transfusion practices across a variety of practice types throughout Australia. Future work is needed to determine how representative these results are of current transfusion practices across Australia, and if so, what can be done to optimise them.

Premedication for Nonemergent Intubation in the NICU: A Call for Standardized Practice.

This paper discusses neonatal endotracheal intubation and the need for standardization in practice regarding the use of premedication. Intubation is common in the NICU because of resuscitation, surfactant administration, congenital anomalies, apnea, and sedation for procedures or surgery. Intubation is both painful and stressful. Unmedicated intubation is associated with several adverse outcomes including repeat and prolonged attempts, airway trauma, bradycardia, severe desaturation, and need for resuscitation. Most providers believe intubation is painful and that premedication should be provided; however, there is still resistance to provide premedication and inconsistency in doing so. Reasons for not providing premedication include concerns about medication side effects such as chest wall rigidity or prolonged respiratory depression inhibiting immediate extubation after surfactant administration. Premedication should include an opioid analgesic for pain, a benzodiazepine for an adjuvant sedation, a vagolytic to decrease bradycardia, and the optional use of a muscle relaxant for paralysis.

Effect of pre-operative medication with paracetamol and ketorolac on the success of inferior alveolar nerve block in patients with symptomatic irreversible pulpitis: a double-blind randomized clinical trial.

BackgroundThe efficacy of local anesthesia decreases in patients with symptomatic irreversible pulpitis. Therefore, it was proposed that the use of premedication with an anti-inflammatory drug might increase the success rate of pulpal anesthesia in mandibular posterior teeth with vital inflamed pulp.MethodsOne hundred thirty-four patients who were actively experiencing pain willingly participated in this study. The Heft Parker (HP) visual analog scale (VAS) was used to record the initial pain intensity. Patients were randomly allocated to receive a placebo, 10 mg of ketorolac, and 650 mg of paracetamol. The standard inferior alveolar nerve block (IANB) was administered to all patients using 2% lidocaine with 1:200,000 adrenaline after one hour of medication. After 15 min, the patient was instructed to rate the discomfort during each step of the treatment procedure, such as access to remaining dentin, access to the pulp chamber, and during canal instrumentation on the HP VAS. IANB was considered successful if the patient reported no or mild pain during access preparation and instrumentation. Moderate or severe pain was classified as a failure of IANB and another method of anesthesia was used before continuing the treatment.ResultsThe rate of successful anesthesia in the placebo, paracetamol, and ketorolac groups was 29%, 33%, and 43%, respectively, and no statistically significant difference was found between the groups.ConclusionPreoperative administration of paracetamol or ketorolac did not significantly affect the success rate of IANB in patients with irreversible pulpitis. No significant difference was observed between the paracetamol and ketorolac groups.