Beneficial Effects of Low-Dose Intravenous Dexmedetomidine Premedication in Patient Undergoing Laparoscopic Cholecystectomy Under General Anesthesia: A Prospective, Double-Blind, Randomized Controlled Trial.

Purpose: Dexmedetomidine (Dex) is a potent and highly selective α2-adrenergic receptor agonist. Within an appropriate dose range, Dex can effectively attenuate the surgical stress response, provide intraoperative hemodynamic stability, and improve the patient recovery quality. High-dose Dex can delay patient awakening from anesthesia and increase the incidence of bradycardia. This randomized controlled trial aimed to investigate the effects of low-dose intravenous Dex premedication in patients undergoing laparoscopic cholecystectomy (LC). Material and Methods: In total, 100 patients undergoing LC were equally randomized into Group C (premedication with saline) and Group D (premedication with 0.5 µg/kg Dex). The patients were premedicated with saline or Dex, depending on the group, before anesthesia induction. Following this, anesthesia induction and endotracheal intubation was performed, and anesthesia was maintained during surgery. Following the completion of the surgery, the patients were transferred the post-anesthesia care unit (PACU) and stayed there until they met the PACU discharge criteria. The hemodynamic parameters, consumption of anesthetics, surgical duration, postoperative awakening time, extubation time, postoperative pain, and complications were recorded. Results: No significant differences were observed in the heart rate (HR) and mean arterial pressure (MAP) between the two groups before premedication (P>0.05). The MAP and HR immediately after endotracheal intubation and immediately after extubation were significantly lower in Group D than in Group C (P<0.05 for both). The incidence of bradycardia was significantly higher in Group D than in Group C (P<0.05), while atropine was used in neither group. Propofol and remifentanil consumption was significantly lower in Group D than in Group C (P<0.05). The postoperative awakening and extubation times were significantly shorter in Group D than in Group C (P<0.05). The postoperative visual analog scale scores for pain and incidence of nausea, vomiting, and cough were significantly lower in Group D than in Group C (P<0.05 for all). Conclusion: Our data suggest that premedication with dexmedetomidine (0.5 µg/kg) before general anesthesia induction can effectively attenuate intraoperative stress response and postoperative pain, maintain perioperative hemodynamic stability, and decrease the incidence of adverse events, which might be an effective and safe anesthetic protocol during LC worthy of further clinical application.

The MAGIC trial: a pragmatic, multicentre, parallel, noninferiority, randomised trial of melatonin versus midazolam in the premedication of anxious children attending for elective surgery under general anaesthesia.

BACKGROUND: Child anxiety before general anaesthesia and surgery is common. Midazolam is a commonly used premedication to address this. Melatonin is an alternative anxiolytic, however trials evaluating its efficacy in children have delivered conflicting results. METHODS: This multicentre, double-blind randomised trial was performed in 20 UK NHS Trusts. A sample size of 624 was required to declare noninferiority of melatonin. Anxious children, awaiting day case elective surgery under general anaesthesia, were randomly assigned 1:1 to midazolam or melatonin premedication (0.5 mg kg-1, maximum 20 mg) 30 min before transfer to the operating room. The primary outcome was the modified Yale Preoperative Anxiety Scale-Short Form (mYPAS-SF). Secondary outcomes included safety. Results are presented as n (%) and adjusted mean differences with 95% confidence intervals. RESULTS: The trial was stopped prematurely (n=110; 55 per group) because of recruitment futility. Participants had a median age of 7 (6-10) yr, and 57 (52%) were female. Intention-to-treat and per-protocol modified Yale Preoperative Anxiety Scale-Short Form analyses showed adjusted mean differences of 13.1 (3.7-22.4) and 12.9 (3.1-22.6), respectively, in favour of midazolam. The upper 95% confidence interval limits exceeded the predefined margin of 4.3 in both cases, whereas the lower 95% confidence interval excluded zero, indicating that melatonin was inferior to midazolam, with a difference considered to be clinically relevant. No serious adverse events were seen in either arm. CONCLUSION: Melatonin was less effective than midazolam at reducing preoperative anxiety in children, although the early termination of the trial increases the likelihood of bias. CLINICAL TRIAL REGISTRATION: ISRCTN registry: ISRCTN18296119.

The Effect of Using Premedication of Simethicone/Pronase With or Without Postural Change on Visualization of the Mucosa Before Endoscopy: A Prospective, Double Blinded, Randomized Controlled Trial.

INTRODUCTION: To investigate the efficacy and safety of preprocedural simethicone (S) and pronase (P) for optimal mucosal visualization during esophagogastroduodenoscopy with sedation. The effect of postural change combined with premedication on mucosal visibility was also examined. METHODS: The study randomized 496 patients into 8 groups based on the type of premedication provided and whether a postural change occurred. The premedication in the control group was 100 mL of normal saline solution (NS). The remaining 3 intervention groups were administered 100 mL of simethicone alone (S), pronase solution alone (P), and simethicone plus pronase solution (S + P). Each group was classified into subgroups according to whether there was a postural change (PC). The mucosal visibility score (MVS), total mucosal visibility score (TVS), procedure time, water consumption for mucosal cleansing, and proportion of patients with diminutive lesions <5 mm were recorded. RESULTS: The P and S groups had a significantly better TVS than the NS group (11.86 ± 3.36 in group P vs 14.52 ± 2.57 in group NS, P < 0.001; 12.36 ± 2.93 in group S vs 14.52 ± 2.57 in group NS, P = 0.006). The TVS was better in the P group than in the S group (11.86 ± 3.36 vs 12.36 ± 2.93, P = 0.037). The MVS was significantly better in the esophagus and duodenum and worse in the upper and lower gastric body in the S group than in the P group. The P + S group had a significantly better TVS than the P and S groups (9.81 ± 2.90 in group P + S vs 11.86 ± 3.36 in group P and 12.36 ± 2.93 in group S, respectively, P < 0.001),\ and had a reduced amount of flushing water during the procedure (0 [interquartile range [IQR]: 0-33] mL in group P + S vs 40 [IQR: 0-70] mL in group P, P < 0.01; 0 [IQR: 0-33] mL in group P + S vs 50 [IQR: 20-98] mL in group S, P < 0.001). The TVS was significantly better in the P + S + PC group than in the P + S group (8.44 ± 2.10 vs 9.81 ± 2.90, P = 0.003). The MVS was significantly better in the gastric antrum, fundus, and upper and lower gastric body in the P + S + PC group than in the P + S group. There was no significant difference in the detection rate of diminutive lesions among the different groups during an endoscopic examination ( P > 0.05). DISCUSSION: The combination of preprocedural administration with simethicone and pronase achieved superior mucosal visualization compared with saline, simethicone, or pronase alone in patients receiving upper endoscopy. Postural change maneuvers performed before endoscopy further improved the mucosal visibility in most parts of the stomach when used with preprocedural simethicone and pronase.

The interest of intranasal clonidine in the prevention of perioperative children's anxiety: a prospective randomized trial.

Introduction: perioperative anxiety in children may lead to psychological and physiological side effects. Clonidine is in increasing use in the pediatric population as an anxiolytic, sedative, and analgesic because of its central alpha2-adrenergic agonist effect. Our study aimed to evaluate the effect of clonidine in the prevention of perioperative children´s anxiety. Methods: we conducted a prospective controlled randomized double-blinded clinical trial including children aged between 2 and 15 years undergoing tonsillectomy surgery. The patients were randomly allocated to receive either an intranasal dose of clonidine (4 µg/kg) (clonidine group) or an equal volume dose of saline solution (control group) 30 minutes before entering the operating room. The level of anxiety assessed using the m-YPAS score was recorded before premedication, at the time of parent-child separation, and at the time of installation in the operating room. Acceptance of premedication, degree of sedation on entering the operating room as well as agitation on awakening, and sedation on arrival post-anesthesia care unit were noted. Adverse effects were recorded during the surgical procedure and in the postoperative recovery room. Results: the number of patients analyzed was 78 with 39 patients in each group. There were no signification differences in demographic data and premedication acceptance between the two groups. Levels of anxiety before any premedication were similar in the two groups. However, the anxiety level 30 minutes after premedication and in the operating room was significantly lower in the clonidine group (p<0.001). Children who received clonidine showed better sedation on entering the operating room (p=0.002) as well as postoperatively on entering the post-anesthesia unit care (p=0.006). The hemodynamic and respiratory parameters recorded were statistically comparable. Conclusion: intranasal clonidine is an interesting premedication to prevent perioperative children´s anxiety with few side effects.

Pharmacologic Adjuncts for Neonatal Tracheal Intubation: The Evidence Behind Premedication.

Premedication such as analgesia, sedation, vagolytics, and paralytics may improve neonatal tracheal intubation success, reduce intubation-associated adverse events, and create optimal conditions for performing this high-risk and challenging procedure. Although rapid sequence induction including a paralytic agent has been adopted for intubations in pediatric and adult critical care, neonatal clinical practice varies. This review aims to summarize details of common classes of neonatal intubation premedication including indications for use, medication route, dosage, potential adverse effects in term and preterm infants, and reversal agents. In addition, this review shares the literature on national and international practice variations; explores evidence in support of establishing premedication guidelines; and discusses unique circumstances in which premedication use has not been established, such as during catheter-based or minimally invasive surfactant delivery. With increasing survival of extremely preterm infants, clear guidance for premedication use in this population will be necessary, particularly considering potential short- and long-term side effects of procedural sedation on the developing brain.

Prospective, randomized, double-blind, double-dummy, active-controlled, phase 3 clinical trial comparing the safety and efficacy of intranasal dexmedetomidine to oral midazolam as premedication for propofol sedation in pediatric patients undergoing magnetic resonance imaging: the MIDEX MRI trial.

BACKGROUND: Children under 6 years who need magnetic resonance imaging usually require sedation to obtain best quality images, but the optimal sedation protocol remains to be determined. In 2018, we showed a 22% interruption in image acquisition during magnetic resonance imaging when performing a propofol-based sedation using a bolus approach. As non-pharmacological premedication is often insufficient to reduce the anxiety of children related to parental separation, pharmacological premedication may be useful to facilitate the induction of anesthesia. In our institution, effective premedication is obtained oral intake of midazolam, though its administration relies on patients' compliance and could also lead to paradoxical reaction. Dexmedetomidine has a safe profile in the pediatric population and can therefore represent an interesting alternative. The primary objective of this trial is to demonstrate the superiority of intranasal dexmedetomidine compared to oral midazolam as premedication in reducing the occurrence of any event requiring temporary or definitive interruption of the examination to allow anesthesiologist intervention in children undergoing magnetic resonance imaging under propofol sedation. METHODS: In this single-center, prospective, randomized, double-blind, double-dummy, active comparator-controlled, superiority trial, we planned to include 250 patients, aged 6 months to 6 years, undergoing a scheduled magnetic resonance imaging requiring the presence of an anesthesiologist. After informed consent, the patients will be randomized to receive either oral midazolam or intranasal dexmedetomidine as premedication. The data will be analyzed in intention to treat, using Kolmogorov-Smirnov Z, chi-square, Wilcoxon, and Mann-Whitney U tests. A P-value < 0.05 will be considered statistically significant. DISCUSSION: The MIDEX MRI study will assess the efficacy of intranasal dexmedetomidine compared to oral midazolam to improve the quality of a propofol-based sedation prior to magnetic resonance imaging, without negative repercussion on the postoperative period. TRIAL REGISTRATION: ClinicalTrial.gov NCT05192629 . Registered on 14 January 2022. Protocol version 2.1.

Comparison of intranasal dexmedetomidine-midazolam, dexmedetomidine-ketamine, and midazolam-ketamine for premedication in paediatric patients: a double-blinded randomized trial.

BACKGROUND: Paediatric patients are a population with a high level of anxiety. The prevention of perioperative stress in a frightened child is important to render the child calm and cooperative for smoother induction. Intranasal premedication is easy and safe, and the drug is rapidly absorbed into the systemic circulation, ensuring early onset of sedation in children and good effectiveness. METHODS: 150 patients in the age group 2-4 years, ASA class I, undergoing elective surgical procedures were enrolled. The patients were randomly divided into 3 groups: a DM group (receiving intranasal dexmedetomidine 1 µg kg -1 and midazolam 0.12 mg kg -1 ), a DK group (receiving intranasal dexmedetomidine 1 µg kg -1 and keta-mine 2 mg kg -1 ), and an MK group (receiving intranasal midazolam 0.12 mg kg -1 and ketamine 2 mg kg -1 ). After 30 minutes of administration of the drugs, the patients were assessed for parent separation anxiety, sedation, ease of IV cannulation, and mask acceptance. RESULTS: The comparison among the 3 groups showed a statistically significant difference for ease of IV cannulation and mask acceptance at 30 minutes, with a P -value of 0.010 with CI of 0.0-0.02, and P -value 0.007 with CI 0.0-0.02, respectively. The parent separation anxiety and sedation score at 30 minutes was statistically insignificant with a P -value of 0.82 with CI of 0.03-0.14 and P -value 0.631 with CI of 0.38-0.58, respectively. CONCLUSIONS: The combination of midazolam and ketamine had a better clinical profile for premedication as compared to other combination drugs used in our study in terms of IV cannulation and acceptance of masks with a comparable decrease in separation anxiety from parents and adequate sedation.

Variability of neonatal premedication practices for endotracheal intubation and LISA in the UK (NeoPRINT survey).

OBJECTIVE: The NeoPRINT Survey was designed to assess premedication practices throughout UK NHS Trusts for both neonatal endotracheal intubation and less invasive surfactant administration (LISA). DESIGN: An online survey consisting of multiple choice and open answer questions covering preferences of premedication for endotracheal intubation and LISA was distributed over a 67-day period. Responses were then analysed using STATA IC 16.0. SETTING: Online survey distributed to all UK Neonatal Units (NNUs). PARTICIPANTS: The survey evaluated premedication practices for endotracheal intubation and LISA in neonates requiring these procedures. MAIN OUTCOME MEASURES: The use of different premedication categories as well as individual medications within each category was analysed to create a picture of typical clinical practice across the UK. RESULTS: The response rate for the survey was 40.8 % (78/191). Premedication was used in all hospitals for endotracheal intubation but overall, 50 % (39/78) of the units that have responded, use premedications for LISA. Individual clinician preference had an impact on premedication practices within each NNU. CONCLUSION: The wide variability on first-line premedication for endotracheal intubation noted in this survey could be overcome using best available evidence through consensus guidance driven by organisations such as British Association of Perinatal |Medicine (BAPM). Secondly, the divisive view around LISA premedication practices noted in this survey requires an answer through a randomised controlled trial.

Efficacy and safety of oral versus intranasal midazolam as premedication in children: a systematic review and meta-analysis.

INTRODUCTION: Midazolam hydrochloride is a widely accepted benzodiazepine for premedication in pediatric patients. However, there is no consistent conclusion regarding which route of administration is best. We performed a meta-analysis to assess the efficacy and safety of oral versus intranasal midazolam premedication in children. EVIDENCE ACQUISITION: The PubMed, Embase, Cochrane Library, and Google Scholar databases were searched from inception to June 2022, for randomized controlled trials comparing oral versus intranasal midazolam. Primary outcomes included satisfactory mask acceptance for induction and satisfactory sedation at separation from parents. Secondary outcomes included the incidence of postoperative nausea and vomiting, incidence of nasal irritation, postoperative recovery time, and hemodynamic changes. EVIDENCE SYNTHESIS: Data from 14 studies involving a total of 901 children were obtained. The results indicated that intranasal and oral midazolam premedication in children provided similar satisfactory mask acceptance for induction (RR, 1.02; 95% CI, 0.93-1.13; P=0.64; I2=0%), satisfactory sedation at separation from parents (RR, 0.99; 95% CI, 0.89-1.10; P=0.90; I2=57%), and postoperative recovery time (WMD, -8.01; 95% CI, -20.16-4.14; P=0.20; I2=85%). Additionally, intranasal midazolam premedication was associated with lower incidence of postoperative nausea and vomiting (RR, 0.70; 95% CI, 0.51-0.96; P=0.03; I2=0%) and shorter onset time. CONCLUSIONS: Differences between intranasal and oral midazolam in satisfactory mask acceptance for induction, satisfactory sedation at separation from parents, and postoperative recovery time were not significant. Intranasal midazolam premedication was associated with shorter onset time and higher incidence of nasal irritation.

Preventive effect of dexamethasone premedication on the development of infusion-related reaction in breast cancer patients receiving trastuzumab.

AIM: To clarify the incidence and risk factors of infusion-related reactions (IRRs) caused by trastuzumab in breast cancer patients and verify the preventive effects of dexamethasone. METHODS: All breast cancer patients newly treated with trastuzumab at the Osaka Medical and Pharmaceutical University Hospital from 1 January 2017 to 31 December 2020 were included. The electronic medical records were retrospectively reviewed. The outcome measure was the occurrence of IRRs of grade 1 or higher during trastuzumab infusion. Only dexamethasone and anticancer drugs administered concomitantly before trastuzumab were used as explanatory variables. RESULTS: The 176 patients included in the study received 2320 infusions. Fifty-eight patients (33.0%) experienced IRRs, and IRRs occurred in 80 (3.4%) of the total 2320 infusions. Owing to the hierarchical structure of the data, the independence of the observed values was evaluated using the intraclass correlation coefficient. Multivariate multilevel logistic regression analysis showed that premedication with dexamethasone lowered the risk of trastuzumab-induced IRRs (mg, per 1 unit, odds ratio [OR] = 0.61, 95% confidence interval [95% CI] 0.43-0.85, P = .003). In addition, preoperative status (OR = 38.9, 95% CI 5.4-278.7, P < .001) and high-dose trastuzumab (mg/kg, per 1 unit, OR = 60.6, 95% CI 20.1-182.9, P < .001) were independent risk factors for IRRs. CONCLUSION: The results of this study suggest that premedication with dexamethasone exhibits preventive effects on trastuzumab-induced IRRs in breast cancer patients. Future studies are needed to determine the optimal dose of dexamethasone to prevent IRRs and the impact of dexamethasone on the efficacy of trastuzumab in breast cancer.

Dextromethorphan premedication in the alleviation of cough during flexible bronchoscopy in adults: A randomized double-blind placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Cough is invariably encountered during flexible bronchoscopy despite sedation and topical anaesthetics. The ideal cough suppressant during flexible bronchoscopy is not known. We assessed the role of dextromethorphan premedication in relieving the cough during flexible bronchoscopy in adults. METHODS: In this single-centre study, we randomized patients aged ≥18 years to receive dextromethorphan syrup 30 ml (90 mg) or an equal volume of placebo 1 h before the procedure. Patients rated their cough severity and discomfort on a visual analogue scale at the end of the procedure. Bronchoscopists also rated cough severity at the end of the procedure. RESULTS: Out of 112 patients screened, 94 patients (median (interquartile range [IQR]) age 51 (36.25-60.75) years, male: female 2.13:1) were randomized to either the dextromethorphan (n = 47) or placebo (n = 47) groups. The patients-rated median (IQR) cough scores at the end of the procedure were 15 (10-23) mm in dextromethorphan versus 20 (12-45.5) mm in placebo groups (p = 0.03). Patients-rated median cough scores at 1 h (5 mm vs. 6 mm, p = 0.21), discomfort scores (12.5 mm vs. 12.5 mm, p = 0.49), and midazolam and lignocaine usage were similar between the two groups. The bronchoscopist-rated median cough score was non-significantly lower in the intervention compared to the placebo (26 mm vs. 35 mm, p = 0.09) groups. CONCLUSION: Dextromethorphan premedication 1 h before flexible bronchoscopy may have an additive effect on cough suppression under conscious sedation and topical lignocaine. Further trials are needed to reiterate our findings with certainty.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Systematic review and meta-analysis comparing the efficacy of dexmedetomidine to midazolam as premedication and a sedative agent in pediatric patients undergoing dental procedures.

INTRODUCTION: Pediatric dental surgeries are associated with the emotions of fear, anxiety, and other behavioral disturbances of children that need to be managed. Sedation using drugs like dexmedetomidine (DEX) and midazolam (MID) is a common pharmacological behavior managing technique. We conducted this meta-analysis to evaluate the efficacy of both these drugs in current literature. METHODOLOGY: A thorough literature search was conducted on PubMed, MEDLINE, Google Scholar, and Cochrane's database for randomized studies that compared sedative efficacy of dexmedetomidine with midazolam in children of 0-15 years of age undergoing dental surgeries. Sedation in children during dental procedure, when used as a premedication, at the time of separation from parents and at the time of mask induction, onset time, duration of anesthesia, and surgery were evaluated. The mean differences (MDs), odds ratio (OR), and their 95% confidence intervals (CIs) were calculated both for continuous and dichotomous outcome data using random-effects model. RESULTS: Seven studies met out inclusion criteria and were analyzed. Results of premedication with DEX was associated with more anxiolysis (OR=0.29, 95% CI: 0.17-0.52, p=0.0001; I2=0%) and at the time of separation from parents (OR=0.36, 95% CI: 0.19-0.69, p=0.002; I2=52%) in comparison to MID. No significant differences in results were seen at mask induction (OR=0.63, 95% CI: 0.34-1.18, p=0.15; I2=47%) and for sedation in children during dental procedures (OR=0.52, 95% CI: 0.07-3.70, p=0.51; I2=72%). Also, there were no significant differences in onset time, duration of anesthesia, and surgery between the two agents. CONCLUSION: DEX proved to be a better premedicant than MID for pediatric patients. No significant difference in efficacy of both sedative agents was observed in children undergoing dental treatment. More clinical trials need to be conducted to see its efficacy in dental surgeries in children of standardized ages and with standard doses.

Efficacy and safety of intranasal ketamine compared with intranasal dexmedetomidine as a premedication before general anesthesia in pediatric patients: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To compare the efficacy and safety of intranasal ketamine with intranasal dexmedetomidine as a premedication in pediatric patients undergoing general anesthesia for elective surgery or other procedures. SOURCE: We conducted a systematic literature search in PubMed, PubMed Central, Scopus, LILACS, Google Scholar, the Cochrane Database of Systematic Reviews, and trial registries for randomized controlled trials (RCTs) comparing intranasal ketamine with intranasal dexmedetomidine as preanesthetic medication in elective surgery or other procedures in pediatric patients. We used Review Manager software version 5.4.1 for statistical analysis and adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We assessed the methodological quality of the included studies with the RoB 2 risk of bias tool. All outcomes were pooled using the Mantle-Haenszel method and a random-effects model. The quality of evidence was assessed using the GRADE approach. PRINCIPAL FINDINGS: Out of 2,445 full texts assessed, we included ten RCTs in the analysis. The efficacy outcomes did not fulfill the comparability criteria between intranasal ketamine and intranasal dexmedetomidine for sedation at parental separation (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.04; I2 = 89%; GRADE evidence, low), mask acceptance (RR, 0.86; 95% CI, 0.66 to 1.13; I2 = 50%; GRADE evidence, low), and iv canulation (RR, 1.16; 95% CI, 0.79 to 1.69; I2 = 69%; GRADE evidence, very low). Intranasal ketamine-treated patients showed a higher incidence of nausea and vomiting (RR, 2.47; 95% CI, 1.24 to 4.91; I2 = 0; GRADE evidence, moderate). Significantly more bradycardia was observed in the intranasal dexmedetomidine group (RR, 0.16; 95% CI, 0.04 to 0.70; I2 = 40%; GRADE evidence, moderate) than in the ketamine group. CONCLUSION: The low to very low-quality evidence in this systematic review and meta-analysis of RCTs neither confirmed nor refuted comparable premedication efficacy of intranasal ketamine and dexmedetomidine in terms of parental separation, mask acceptance, and iv cannulation in a pediatric population. Clinical decision-making is likely to be influenced by differences in gastrointestinal and cardiovascular safety profiles. STUDY REGISTRATION: PROSPERO (CRD42021262516); registered 22 July 2021.

RéSUMé: OBJECTIF: Comparer l'efficacité et l'innocuité de la kétamine intranasale à la dexmédétomidine intranasale comme prémédication chez les patients pédiatriques bénéficiant d'une anesthésie générale pour une chirurgie élective ou d'autres interventions. SOURCES: Nous avons réalisé une recherche documentaire systématique dans les bases de données PubMed, PubMed Central, Scopus, LILACS, Google Scholar, ainsi que dans la base de données Cochrane des revues systématiques et dans les registres d'études pour en tirer les études randomisées contrôlées (ERC) comparant la kétamine intranasale à la dexmédétomidine intranasale comme médicament préanesthésique en chirurgie élective ou pour d'autres interventions chez les patients pédiatriques. Nous avons utilisé la version 5.4.1 du logiciel Review Manager pour l'analyse statistique et nous nous sommes conformés aux lignes directrices PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Nous avons évalué la qualité méthodologique des études incluses à l'aide de l'outil d'évaluation du risque de biais RoB 2. Tous les résultats ont été regroupés à l'aide de la méthode Mantle-Haenszel et d'un modèle à effets aléatoires. La qualité des données probantes a été évaluée à l'aide de l'approche GRADE. CONSTATATIONS PRINCIPALES: Sur les 2445 textes intégraux évalués, nous avons inclus dix ERC dans l'analyse. Les critères d'efficacité ne remplissaient pas les critères de comparabilité entre la kétamine intranasale et la dexmédétomidine intranasale pour la sédation lors de la séparation des parents (risque relatif [RR], 0,90; intervalle de confiance [IC] à 95 %, 0,79 à 1,04; I2 = 89 %; qualité des données probantes selon GRADE, faible), acceptation du masque (RR, 0,86; IC 95 %, 0,66 à 1,13; I2 = 50 %; qualité des données probantes selon GRADE, faible) et canulation IV (RR, 1,16; IC 95 %, 0,79 à 1,69; I2 = 69 %; qualité des données probantes selon GRADE, très faible). Les patients traités par kétamine intranasale ont montré une incidence plus élevée de nausées et vomissements (RR, 2,47; IC 95%, 1,24 à 4,91; I2 = 0; qualité des données probantes selon GRADE, modérée). Une proportion significativement plus élevée de cas de bradycardie a été observée dans le groupe dexmédétomidine intranasale (RR, 0,16; IC 95%, 0,04 à 0,70; I2 = 40 %; qualité des données probantes selon GRADE, modérée) comparativement au groupe kétamine. CONCLUSION: Les données probantes de qualité faible à très faible de cette revue systématique et méta-analyse des ERC n'ont ni confirmé ni infirmé l'efficacité comparable de la prémédication par kétamine ou dexmédétomidine intranasale, que ce soit en termes de séparation parentale, d'acceptation du masque ou de canulation IV dans une population pédiatrique. La prise de décision clinique est susceptible d'être influencée par les différences dans les profils d'innocuité gastro-intestinale et cardiovasculaire. ENREGISTREMENT DE L'éTUDE: PROSPERO (CRD42021262516); enregistrée le 22 juillet 2021.

Histamine-2 (H2 ) antagonists can be safely removed from standard paclitaxel premedication regimens.

AIMS: The aim of this study is to investigate the rates of hypersensitivity reactions (HSRs) in patients receiving paclitaxel chemotherapy, with and without a histamine-2 (H2 ) antagonists. METHOD: This prospective, multi-centre, cohort study compared patients receiving paclitaxel treated with premedication regimens containing chlorphenamine, dexamethasone and an H2 antagonist vs patients treated without an H2 antagonist. Rates of HSRs were described and logistic multivariable regression was used to investigate any associations with H2 antagonist treatment, adjusting for confounding variables. RESULTS: A total of 1043 individuals were included in the study; of these, 638 (61%) patients received an H2 antagonist and 405 (49%) were not given an H2 antagonist. Incidence of HSR in the cohort treated with H2 antagonists was 11.31% (n = 70) vs 9.86% (n = 41) in the cohort without. There was no statistically significant difference between the rates of HSR observed in those receiving and not receiving an H2 antagonist (odds ratio 1.04, 95% CI 0.65, 1.66, P = .9). CONCLUSIONS: Results presented within the study are consistent with other recently published evidence to suggest that H2 antagonists do not confer any advantage as part of premedication regimens in reducing the incidence of HSR in patients treated with paclitaxel.

Best Evidence-Based Dosing Recommendations for Dexmedetomidine for Premedication and Procedural Sedation in Pediatrics: Outcome of a Risk-Benefit Analysis By the Dutch Pediatric Formulary.

BACKGROUND: Dexmedetomidine is currently off-label for use in pediatric clinical care worldwide. Nevertheless, it is frequently prescribed to pediatric patients as premedication prior to induction of anesthesia or for procedural sedation. There is ample literature on the pharmacokinetics, efficacy and safety of dexmedetomidine in this vulnerable patient population, but there is a general lack of consensus on dosing. In this project, we aimed to use the standardized workflow of the Dutch Pediatric Formulary to establish best evidence-based pediatric dosing guidelines for dexmedetomidine as premedication and for procedural sedation. METHOD: The available literature on dexmedetomidine in pediatrics was reviewed in order to address the following three questions: (1) What is the right dose? (2) What is known about efficacy? (3) What is known about safety? Relevant literature was compiled into a risk-benefit analysis document. A team of clinical experts critically appraised the analysis and the proposed dosing recommendations. RESULTS: Dexmedetomidine is most commonly administered via the intravenous or intranasal route. Clearance is age dependent, warranting higher doses in infants to reach similar exposure as in adults. Dexmedetomidine use results in satisfactory sedation at parent separation, adequate sedation and a favorable recovery profile. The safety profile is good and comparable to adults, with dose-related hemodynamic effects. CONCLUSION: Following the structured approach of the Dutch Pediatric Formulary, best evidence-based dosing recommendations were proposed for dexmedetomidine, used as premedication prior to induction of anesthesia (intranasal dose) and for procedural sedation (intranasal and intravenous dose) in pediatric patients.

Premedication Protocols to Prevent Hypersensitivity Reactions to Chemotherapy: a Literature Review.

Hypersensitivity reactions (HSRs) to chemotherapy may prevent patients from receiving the most effective therapy. This review was undertaken to identify evidence-based preventive premedication strategies that reduce the likelihood of HSR in the first instance and improve the safety of subsequent infusions in patients who have demonstrated HSR to a certain class of chemotherapy. PubMed was searched until October 2021 using the key words: "hypersensitivity to chemotherapeutic drugs," "hypersensitivity to antineoplastic agents," "taxanes hypersensitivity," "platinum compound hypersensitivity," "premedication," "dexamethasone," "prednisone," "hydrocortisone," "antihistamine," "diphenhydramine," "cetirizine," "famotidine," "meperidine," "aspirin," "ibuprofen," and "montelukast." The search was restricted to articles published in English. A total of 73 abstracts were selected for inclusion in the review. Most premedication regimens have been derived empirically rather than determined through randomized trials. Based on the available evidence, we provide an update on likely HSR mechanisms and a practical guide for classifying systemic HSR. The evidence indicates that a combination of prevention strategies using newer antihistamines, H2 antagonists, leukotriene receptor antagonists, and corticosteroids and other interventions used judiciously reduces the occurrence and severity of HSR and improves safety.

Oxaliplatin immune-mediated thrombocytopenia: Is there a role for premedication or desensitization?

Oxaliplatin is a common chemotherapy agent that is used in the treatment of multiple solid malignancies. Immune-mediated thrombocytopenia is a rare and potentially life-threatening adverse effect of oxaliplatin that is characterized by severe thrombocytopenia, which may be accompanied by overt bleeding. This adverse effect is probably mediated via anti-platelet antibodies that become reactive in the presence of oxaliplatin. Due to its rarity and severity, information is scarce regarding the effect of desensitization or attempts at rechallenge after prolonged withdrawal of oxaliplatin. This short report describes 3 cases of oxaliplatin immune-mediated thrombocytopenia, including a case occurring under desensitization protocol and a case of recurrence after a prolo nged withdrawal. All 3 patients are female, have prolonged exposures to oxaliplatin and were all treated for metastatic colorectal cancer. Physicians should be aware of oxaliplatin immune-mediated thrombocytopenia as symptoms may appear rapidly. Oxaliplatin should be permanently discontinued for patients experiencing this adverse effect, as recurrence is highly likely even in the setting of desensitization.

Time to desaturation in preterm infants undergoing endotracheal intubation.

BACKGROUND: Neonatal endotracheal intubation is often associated with physiological instability. The Neonatal Resuscitation Program recommends a time-based limit (30 s) for intubation attempts in the delivery room, but there are limited physiological data to support recommendations in the neonatal intensive care unit (NICU). We aimed to determine the time to desaturation after ceasing spontaneous or assisted breathing in preterm infants undergoing elective endotracheal intubation in the NICU. METHODS: Observational study at The Royal Women's Hospital, Melbourne. A secondary analysis was performed of video recordings of neonates ≤32 weeks' postmenstrual age undergoing elective intubation. Infants received premedication including atropine, a sedative and muscle relaxant. Apnoeic oxygenation time (AOT) was defined as the time from the last positive pressure or spontaneous breath until desaturation (SpO2 <90%). RESULTS: Seventy-eight infants were included. The median (IQR) gestational age at birth was 27 (26-29) weeks and birth weight 946 (773-1216) g. All but five neonates desaturated to SpO2 <90% (73/78, 94%). The median (IQR) AOT was 22 (14-32) s. The median (IQR) time from ceasing positive pressure ventilation to desaturation <80% was 35 (24-44) s and to desaturation <60% was 56 (42-68) s. No episodes of bradycardia were seen. CONCLUSIONS: This is the first study to report AOT in preterm infants. During intubation of preterm infants in the NICU, desaturation occurs quickly after cessation of positive pressure ventilation. These data are important for the development of clinical guidelines for neonatal intubation. TRIAL REGISTRATION NUMBER: ACTRN12614000709640.

Sentinel lymph node biopsy in patients with endometrial cancer and an indocyanine green or iodinated contrast reaction - A proposed management algorithm.

OBJECTIVE: To describe the incidence of adverse reactions to indocyanine green (ICG) administered during sentinel lymph node (SLN) biopsy for endometrial cancer, and to propose an ICG management algorithm for these patients. METHODS: All patients who underwent surgery for endometrial cancer with SLN biopsy using ICG from 1/2017 to 8/2020 were identified using a single-institution prospective database. Surgical adverse events (SAEs) related to the procedure were identified. A review of the literature was performed. RESULTS: In all, 1414 patients met inclusion criteria and were evaluated. Sixty-seven (4.7%) patients had a history of either an iodine or contrast allergy. No patients had a history of documented ICG allergy. Among patients with an iodine or contrast allergy, 65 (97%) received a corticosteroid with or without diphenhydramine prior to ICG administration. One hundred five patients (7.4%) experienced 116 SAEs. Among these patients, 3 experienced potentially allergic SAEs possibly related to ICG administration. After thorough chart review, however, the likelihood these SAEs were due to ICG appeared low. No patients experienced an anaphylactic response after ICG admission. CONCLUSION: There were no anaphylactic reactions to ICG intracervical administration during 1414 consecutive SLN biopsies, including in patients with a documented iodine or contrast allergy. Intracervical injection of ICG is safe, and premedication using corticosteroids with or without diphenhydramine prior to SLN biopsy is a reasonable strategy in patients with iodinated contrast allergy.