Effect of Premedication With Pronase Before Upper Gastrointestinal Endoscopy: A Multicenter Prospective Randomized Controlled Study.

OBJECTIVES: This study aimed to confirm whether premedication with pronase before endoscopy improves mucosal visualization and increases precancerous lesion and cancer lesion detection rates. MATERIALS AND METHODS: From June 2018 to April 2019, out-patients scheduled for endoscopy from 13 hospitals were screened to be randomly allocated in a 2:1 ratio to premedication with pronase (group A) and water (group B). The primary endpoint was mucosal visibility scores, and the secondary endpoint was precancerous and cancer lesion detection rates. This trial was registered at Chinese Clinical Trial Registry, and the registration number was ChiCTR1800016853. RESULTS: Group A showed significantly lower mucosal visibility scores (better mucosal visibility) of esophagus, stomach, and duodenum than group B, with all P -values <0.001. The overall cancer detection rates between group A and group B were 0.83 and 1.08%, and overall detection rates of precancerous and cancer lesion were 4.4 and 4.9%, both without significant difference ( P =1.000 and 0.824). In addition, the flushing volume (milliliter) of group A (10.52±23.41) was less than group B (36.30±52.11) ( P <0.001), and the flushing frequency of group A (0.46±1.01) was fewer than group B (1.62±2.12) ( P <0.001). CONCLUSIONS: Premedication with pronase could achieve better mucosal visibility and decrease flushing frequency and volume, but may not increase lesion detection rates.

A quality improvement initiative standardizing premedication for blood product transfusions.

For children with cancer, blood product transfusions are crucial, but can be complicated by transfusion reactions. To prevent these complications, premedication is often given, although not always evidence-based. Herein, we describe a significant decrease in the use of premedication (72%-28%) at our institution after the implementation of standardized guidelines, without an increase in transfusion reactions (3.2% prior vs. 1.5% after standardization). Importantly, there were no severe transfusion reactions leading to hospitalization or death. Our results provide evidence in favor of more judicious use of premedication prior to transfusions in patients 21 years and younger being treated for cancer.

Steroid Premedication and Monoclonal Antibody Therapy: Should We Reconsider?

OPINION STATEMENT: Monoclonal antibody (mAb) therapy is now considered a main component of cancer therapy in Australia. Although traditionally thought of as pure signalling inhibitors, a large proponent of these medications function through antibody-dependent cell-mediated cytotoxicity (ADCC). Currently, most protocols and institutional guidelines for ADCC-mediated mAbs promote the use of corticosteroids as premedication: this is implemented to reduce infusion-related reactions (IRRs) and antiemesis prophylaxis and combat concurrently administered chemotherapy-related syndromes. Concerningly, the inhibitory effects of ADCC by corticosteroids are well documented; henceforth, it is possible the current standard of care is misaligned to the literature surrounding ADCC. Subsequently, clinicians' decisions to act in contrast to this literature may be reducing the efficacy of mAbs. The literature suggests that the redundant use of corticosteroids should be cautioned against when used in conjunction with ADCC-mediated mAbs-this is due to the consequent reduction in anti-tumour activity. Owing to the fact IRRs typically occur upon initial infusion, the authors advocate for individual clinicians and institutional protocols to considering augmenting their practice to corticosteroid premedication at the first dose only, unless clinically indicated. Additionally, product information (PI) and consumer medicine information (CMI) documents distributed by Australian and international regulatory agencies should consider disclosing the risk of concurrent steroids with these medications. Moreover, the authors suggest considering alternative medications for the management of side effects.

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.

Overview of premedication prescription and intake in an oncology day hospital: What do we need to change to improve patient management?

BACKGROUND: Premedication of cancer therapy against nausea and vomiting (NV) and hypersensitivity reaction (HS) is essential for good patient management. However, this prescription is not always optimal. Today, as a large part of cancer therapies are administered in day hospitals (DH), premedication taken on the day of the cancer treatment is injected as a 30-min infusion. OBJECTIVE: To assess compliance with recommendations for premedication prescription and intake; to analyse patient attitude about switching to exclusively oral forms taken at home. METHOD: The study is conducted in the medical oncology DH of a French Hospital from 17 January to 25 February 2022. The data collection is carried out as an individual interview, associated with the distribution of two questionnaires. Data are coupled with the premedication set up on our software and the last medical report. Intakes are considered optimal when recommendations, tolerance, background, and adherence of the patient are taken into account. RESULTS: Seventy patients were included for interviews. Regarding software prescriptions, our configuration was consistent with recommendations in 100% of cases for HS and 37% for NV. Intakes were compliant in 51.4% of cases, non-compliant in 17.1% and debatable in 31.5%. Disparities between the practices of different physicians were identified. Regarding the feasibility of oral substitution, it could concern 63.5% of patients. CONCLUSION: This work makes it possible to improve the management of all patients and to make the operation of the care unit more fluid.

Impact of institutional interventions on the rate of paclitaxel hypersensitivity reactions.

PURPOSE: Paclitaxel is associated with hypersensitivity reactions (HSRs). Intravenous premedication regimens have been devised to decrease the incidence and severity of HSRs. At our institution oral histamine 1 receptor antagonists (H1RA) and histamine 2 receptor antagonists (H2RA) were adopted as standard. Standardizations were implemented for consistent premedication use in all disease states. The purpose of this retrospective study was to compare the incidence and severity of HSRs before and after standardization. METHODS: Patients who received paclitaxel from 20 April 2018 to 8 December 2020 having an HSR were included in analysis. An infusion was flagged for review if a rescue medication was administered after the start of the paclitaxel infusion. The incidences of all HSR prior to and post-standardization were compared. A subgroup analysis of patients receiving paclitaxel for the first and second time was performed. RESULTS: There were 3499infusions in the pre-standardization group and 1159infusions in the post-standardization group. After review, 100 HSRs pre-standardization and 38 HSRs post-standardization were confirmed reactions. The rate of overall HSRs was 2.9% in the pre-standardization group and 3.3% in the post-standardization group (p = 0.48). HSRs, during the first and second doses of paclitaxel, occurred in 10.2% of the pre-standardization and 8.5% of the post-standardization group (p = 0.55). CONCLUSIONS: This retrospective interventional study demonstrated that same-day intravenous dexamethasone, oral H1RA, and oral H2RA are safe premedication regimens for paclitaxel. No change in the severity of reactions was seen. Overall, better adherence to premedication administration was seen post-standardization.

Premedication strategy in cetuximab rechallenge after Grade 2 hypersensitivity reactions.

INTRODUCTION: Cetuximab, an IgG1 monoclonal antibody, is utilized in the treatment of metastatic colorectal cancer and squamous cell head and neck cancers. Due to the risk of hypersensitivity reactions, standard premedication with a histamine-1 (H-1) antagonist is recommended prior to administration, however, there is less guidance for premedication strategies to assist with rechallenge after infusion reactions. Here, we describe two cases of successful cetuximab treatment after Grade 2 reactions, in addition to risk factors and proposed premedication strategies for successful rechallenge. CASE REPORT: Two patients who experienced Grade 2 hypersensitivity reactions were both successfully rechallenged with increased premedications 1-2 weeks after initial infusions. The first patient was a 56-year-old male diagnosed with metastatic colorectal cancer receiving cetuximab as part of a clinical trial. The second patient was a 73-year-old male diagnosed with head and neck cancer receiving cetuximab as part of standard of care concurrent with radiation. MANAGEMENT AND OUTCOME: Each patient was rechallenged with an increased premedication strategy including dexamethasone, famotidine, diphenhydramine, and acetaminophen in addition to reducing the infusion rate. Both patients either continued treatment or successfully completed therapy, without any additional infusion-related reactions. DISCUSSION: We aimed to review risk factors related to cetuximab infusion reactions and propose a premedication strategy for rechallenge postreaction. Known risk factors include male sex and the accumulation of cetuximab-specific IgE. These may be mitigated by the addition of increased premedication with dexamethasone and famotidine with concurrent reduced infusion rate.

Comparison of the efficacy of intranasal atomised dexmedetomidine versus intranasal atomised ketamine as a premedication for sedation and anxiolysis in children undergoing spinal dysraphism surgery: A randomized controlled trial.

BACKGROUND: Preoperative anxiety leads to adverse clinical outcomes and long-term maladaptive behavioural changes. The role of intranasal atomised dexmedetomidine and atomised ketamine as premedication to produce sedation and anxiolysis in paediatric neurosurgical patients has not been extensively studied. OBJECTIVE: To study the efficacy of intranasal atomised dexmedetomidine and intranasal atomised ketamine as premedication in producing sedation and facilitating smooth induction in children undergoing spinal dysraphism surgery. DESIGN: A prospective randomised double-blind trial. SETTING: A tertiary teaching hospital. PATIENTS: Sixty-four children aged 1 to 10 years undergoing spinal dysraphism surgery. METHODS: Children were randomised to receive intranasal atomised dexmedetomidine 2.5 µg kg -1 (Group D, n  = 32) and intranasal atomised ketamine 5 mg kg -1 (Group K, n  = 32) 30 min before surgery. OUTCOMES MEASURED: The primary outcome was to compare the level of sedation in both groups using the University of Michigan Sedation Score (UMSS). The secondary outcomes included an assessment of the ease of parental separation, intravenous cannulation and satisfactory mask acceptance along with perioperative vitals (heart rate, blood pressure and oxygen saturation). The incidence of emergence agitation and time to discharge were also noted. RESULTS: The degree of sedation was significantly better in Group D as compared to Group K at 20 min (UMSS, 1.55 ±â€Š0.51 versus 1.13 ±â€Š0.34, difference, -0.406; 95% CI, -0.621 to -0.191; P  = 0.0001) and 30 min (2.32 ±â€Š0.6 versus 1.94 ±â€Š0.50, difference, -0.374; 95% CI, -0.650 to -0.100; P  = 0.007). The ease of parental separation, venous cannulation and mask acceptance ( P  = 0.83, 0.418 and 0.100 respectively) were comparable in both groups. The heart rate was lower in group D at 10, 20 and 30 min post-drug administration but was clinically insignificant. The incidence of emergence agitation and time to discharge was also similar with no adverse events reported. CONCLUSION: Intranasal atomised dexmedetomidine produces greater sedation as compared to intranasal atomised ketamine with comparable ease of parental separation, venous cannulation and mask acceptance with no adverse effects.

Effects of tasipimidine premedication with and without methadone and dexmedetomidine on cardiovascular variables during propofol-isoflurane anaesthesia in Beagle dogs.

OBJECTIVE: To evaluate cardiovascular effects of oral tasipimidine on propofol-isoflurane anaesthesia with or without methadone and dexmedetomidine at equianaesthetic levels. STUDY DESIGN: Prospective, placebo-controlled, blinded, experimental trial. ANIMALS: A group of seven adult Beagle dogs weighing (mean ± standard deviation) 12.4 ± 2.6 kg and a mean age of 20.6 ± 1 months. METHODS: The dogs underwent four treatments 60 minutes before induction of anaesthesia with propofol. PP: placebo orally and placebo (NaCl 0.9%) intravenously (IV); TP: tasipimidine 30 µg kg-1 orally and placebo IV; TMP: tasipimidine 30 µg kg-1 orally and methadone 0.2 mg kg-1 IV; and TMPD: tasipimidine 30 µg kg-1 orally with methadone 0.2 mg kg-1 and dexmedetomidine 1 µg kg-1 IV followed by 1 µg kg-1 hour-1. Isoflurane in oxygen was maintained for 120 minutes at 1.2 individual minimum alveolar concentration preventing motor movement. Cardiac output (CO), tissue blood flow (tbf), tissue oxygen saturation (stO2) and relative haemoglobin content were determined. Arterial and mixed venous blood gases, arterial and pulmonary artery pressures and heart rate (HR) were measured at baseline; 60 minutes after oral premedication; 5 minutes after IV premedication; 15, 30, 60, 90 and 120 minutes after propofol injection; and 30 minutes after switching the vaporiser off. Data were analysed by two-way anova for repeated measures; p < 0.05. RESULTS: Tasipimidine induced a significant 20-30% reduction in HR and CO with decreases in MAP (10-15%), tbf (40%) and stO2 (43%). Blood pressure and oxygenation variables were mainly influenced by propofol-isoflurane-oxygen anaesthesia, preceded by short-lived alterations related to IV methadone and dexmedetomidine. CONCLUSIONS AND CLINICAL RELEVANCE: Tasipimidine induced mild to moderate cardiovascular depression. It can be incorporated into a common anaesthetic protocol without detrimental effects in healthy dogs, when anaesthetics are administered to effect and cardiorespiratory function is monitored.

Optimising the oral midazolam dose for premedication in people with intellectual disabilities and/or autism spectrum disorder.

BACKGROUND: In people with intellectual disabilities and/or autism spectrum disorder, oral midazolam (OM) is very effective as premedication for facilitating medical treatment. In this retrospective study, we investigated the optimal dosage of OM for premedication. METHODS: Patients with intellectual disability and/or autism spectrum disorder who were given OM as a premedication were selected from anaesthesia records. The primary outcome variable was the dose of OM (mg/kg) required to produce an adequate sedation. RESULTS: The mean OM dose required was 0.32 ± 0.10 mg/kg. The required OM dose decreased significantly as age and weight increased, and age and weight were also shown to be significantly associated with the dose of OM in the multivariate linear regression analysis. CONCLUSION: The dosage of OM to achieve adequate sedation should decrease as the patient ages. Furthermore, adequate sedation can be achieved with even lower doses of OM in obese people.

The Effect of Clonidine Premedication on Hemodynamic Changes Following Tracheal Intubation and Co2 Gas Insufflation and Postoperative Shivering In Patients Undergoing Laparoscopic Cholecystectomy; a Randomized Clinical Trial.

BACKGROUND: Laparoscopic cholecystectomy is a proper treatment for cholecystitis but the Carbon dioxide gas which is used in surgery stimulates the sympathetic system and causes hemodynamic changes and postoperative shivering in patients undergoing operations. This study was conducted to evaluate the effects of clonidine on reducing hemodynamic changes during tracheal intubation and Carbon dioxide gas insufflation and postoperative shivering in patients undergoing laparoscopic cholecystectomy. MATERIAL AND METHODS: This prospective, randomized, triple-blind clinical trial was conducted on 60 patients between the 18-70 years-old age group, who were candidates of laparoscopic cholecystectomy surgery. The patients randomized into two groups (30 patients received 150 µg oral clonidine) and 30 patients received 100 mg oral Vitamin C). Heart rate and mean arterial pressure of patients were recorded before anesthesia, before and after laryngoscopy, before and after Carbon dioxide gas insufflation. Data were analyzed using Chi-2, student t-test, and analysis of variance by repeated measure considering at a significant level less than 0.05. RESULTS: The findings of this study showed that both heart rate and mean arterial pressure in clonidine group after tracheal intubation and Carbon dioxide gas insufflation were lower than patients in the placebo group, but there was not any statistically significant difference between the two groups (p>0.05) and also postoperative shivering was not different in groups. There was no significant statistical difference in postoperative shivering between the two groups (p>0.05). CONCLUSION: Using 150 µg oral clonidine as a cheap and affordable premedication in patients undergoing laparoscopic cholecystectomy improves hemodynamic stability during operation.

The utility of H2 receptor antagonists in preventing infusion-related reactions to paclitaxel chemotherapy.

BACKGROUND: Paclitaxel has a risk of infusion-related reactions (IRRs) and despite no prospective evidence, is often given with premedication including a corticosteroid, H1 antagonist, and H2 antagonist (H2RA). Backorders impacted the supply of intravenous H2RAs at our center, and it was removed as routine premedication. The authors compared the incidence of IRR in patients treated without H2RA to patients receiving standard H2RA premedication. METHODS: The authors reviewed outpatients starting paclitaxel at the Ottawa Hospital from December 2019 to October 2021. Two cohorts were created: patients treated without H2RA premedication (intervention), and those receiving standard H2RA (control). Demographics, treatment, and IRR information were collected retrospectively. Primary end point was rate of grade ≥2 IRRs during first two doses of paclitaxel. RESULTS: A total of 182 patients were treated without H2RA premedication, compared to 184 control patients treated during non-backorder periods. Baseline characteristics included: median age, 63 years; 86% female; and primary tumor 52% breast/24% gynecologic/10% gastric/esophageal/8% lung/6% other. There were no significant differences between cohorts in baseline characteristics. There was no difference in the rate of grade ≥2 IRR between cohorts; 12.1% (22 of 182; 95% confidence interval [CI], 7.7%-17.7%) for patients treated without H2RA, and 15.1% (28 of 185; 95% CI, 10.3%-21.1%) for control patients. The rate of grade ≥3 IRRs were also similar, 4.4% in intervention cohort versus 3.8% in control cohort. CONCLUSIONS: The removal of H2RAs from premedication for paclitaxel did not result in an increased incidence of IRRs. The use of H2RAs in preventing IRRs to paclitaxel should be re-evaluated.

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.

Impact of histamine-2 antagonist shortage on the incidence of hypersensitivity reactions to paclitaxel: a reconsideration of premedication protocols in France (PACLIREACT Study).

PURPOSE: An international shortage of ranitidine led to adjustments in premedication regimens for paclitaxel-based chemotherapy in early October 2019. In this study, we implemented and evaluated an anti-allergic protocol without histamine-2 antagonists (H2As) and aimed to assess the risk of hypersensitivity reactions (HSRs) to the different premedication regimens used. METHODS: We conducted a single-center observational retrospective study of paclitaxel administrations (7173 administrations in 831 patients). Between January 2019 and December 2020, all allergies reported were recorded. A mixed logistic regression model was implemented to predict the risk of allergy at each injection and to account for repeated administration per patient. RESULTS: A total of 27 HSRs occurred in 24 patients. No protective effect was observed for H2A when comparing paclitaxel injections with H2A premedication versus without H2A (OR = 1.12, p = 0.84). There was also no significant difference in risk of HSR for famotidine versus ranitidine (OR = 0.79, p = 0.78). However, the risk of HSRs was significantly lower for paclitaxel injections with corticosteroids than for those without (OR = 0.08, p = 0.03). In addition, the risk of HSR was significantly higher for the first, second, or third paclitaxel injections than for the subsequent injections (OR = 10.1, p < 0.001). CONCLUSION: We did not find substantial evidence of an increased risk of HSR due to the absence of H2A in the premedication protocols for paclitaxel. Thus, in contrary to the existing literature on paclitaxel, our findings support the use of a premedication protocol without H2A.

Do Children With an Allergic Transfusion Reaction Require Premedication For All Blood Products?

BACKGROUND: Children with a history of allergic transfusion reactions (ATRs) receive antihistamine premedication with or without hydrocortisone to prevent subsequent reactions. We aim to examine the frequency of developing ATRs to subsequent different blood product type transfusions. METHODS: A retrospective chart review of children who received blood product transfusions (packed red blood cells, platelets, frozen plasma, intravenous immunoglobin, albumin, and cryoprecipitate) and developed ATRs. Cases were identified through Transfusion Transmitted Injuries Surveillance System- Ontario database with a complementary chart review. Demographics and subsequent transfusions records were described. RESULTS: During this period, 35,925 blood products were transfused to 4153 patients. Thirty-eight ATRs were reported in 30 patients. All ATRs were minor except 1 anaphylaxis to albumin transfusion. Seven patients (23%) developed multiple ATRs, and all of them were of the same blood product type. A total of 60 subsequent different blood product types were transfused to the 7 patients who had multiple ATRs; none of those transfusions caused ATR. CONCLUSION: In children with a history of ATR, developing a reaction to a different blood product type is rare. Hence, premedicating those transfusions is not warranted.

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.

Effect of midazolam in autism spectrum disorder: A retrospective observational analysis.

BACKGROUND: While midazolam is commonly used as premedication for uncooperative patients, its effects are difficult to predict in patients with autism spectrum disorder for whom abnormalities in gamma-aminobutyric acid have been reported. This study aimed to investigate the influence of autism spectrum disorder on the effect of midazolam when used as premedication. METHODS: This retrospective observational study was performed between April 2017 and August 2018. Before inducing general anesthesia with sevoflurane for dental treatment, 390 uncooperative patients received premedication with midazolam. Ordinal logistic regression analysis was performed with the Observer's Assessment of Alertness/Sedation score 30 min after premedication as the objective variable. Age, sex, American Society of Anesthesiologists physical status class, premedication route, dose per body weight, presence of specific disorders (autism spectrum disorder, intellectual disability, epilepsy, cerebral palsy, and other psychiatric disorders), and regular benzodiazepine or non-benzodiazepine psychotropic administration were included as explanatory variables. Kendall's rank correlation coefficient was used to assess the correlation between the Observer's Assessment of Alertness/Sedation score and cooperation level (1, obvious negative response; 2, negative response; 3, positive reaction; 4, obvious positive reaction) during admission and inhalation induction. All data were extracted from anesthesia and medical records. RESULTS: Age (odds ratio 1.437 [95% confidence interval (CI) 1.213-1.708], P < .001), autism spectrum disorder (1.318 [1.079-1.612], P = .007), benzodiazepine medication (0.574 [0.396-0.827], P = .002), and intramuscular route (1.478 [1.137-1.924], P = .004) were significantly associated with the Observer's Assessment of Alertness/Sedation score, while the score was negatively associated with cooperation levels during admission (τ = -0.714, P < .001) and inhalation induction (τ = -0.606, P < .001). CONCLUSIONS: Patients with autism spectrum disorder may be susceptible to premedication with midazolam; however, regular benzodiazepine administration may reduce the effect.

Median effective dose of esketamine for intranasal premedication in children with congenital heart disease.

BACKGROUND: Esketamine is commonly used as a premedication for its sedation effect. However, the proper dosage for intranasal use in children with congenital heart disease (CHD) has not been determined. This study aimed to estimate the median effective dose (ED50) of esketamine for intranasal premedication in children with CHD. METHODS: Thirty-four children with CHD who needed premedication in March 2021 were enrolled. Intranasal esketamine was initiated at a dose of 1 mg/kg. Based on the outcome of sedation in the previous patient, the dose for the subsequent patient was either increased or reduced by 0.1 mg/kg, which was adjusted between each child. Successful sedation was defined as a Ramsay Sedation Scale score ≥ 3 and Parental Separation Anxiety Scale score ≤ 2. The required ED50 of esketamine was calculated using the modified sequential method. Non-invasive blood pressure, heart rate, saturation of peripheral oxygen, sedation onset time, and adverse reactions were recorded at 5 min intervals after drug administration. RESULTS: The 34 children enrolled had a mean age of 22.5 ± 16.4 (4-54) months and a mean weight of 11.2 ± 3.6 (5.5-20.5) kg; American Society of Anesthesiologists classification I-III. The ED50 of intranasal S(+)-ketamine (esketamine) required for preoperative sedation in pediatric patients with CHD was 0.7 (95% confidence interval: 0.54-0.86) mg/kg, and the mean sedation onset time was 16.39 ± 7.24 min. No serious adverse events, such as respiratory distress, nausea, and vomiting were observed. CONCLUSIONS: The ED50 of intranasal esketamine was 0.7 mg/kg, which was safe and effective for preoperative sedation in pediatric patients with CHD. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry Network (ChiCTR2100044551) on 24/03/2021.

Melatonin or its analogs as premedication to prevent emergence agitation in children: a systematic review and meta-analysis.

BACKGROUND: Emergence agitation (EA) is a prevalent complication in children following general anesthesia. Several studies have assessed the relationship between melatonin or its analogs and the incidence of pediatric EA, yielding conflicting results. This meta-analysis aims to assess the effects of premedication with melatonin or its analogs on preventing EA in children after general anesthesia. METHODS: PubMed, EMBASE, the Cochrane Library, ProQuest Dissertations & Theses Global, Web of Science, CNKI, Wanfang Data, clinicaltrials.gov, and WHO International Clinical Trials Registry Platform were searched until 25 November 2022. We included randomized controlled trials that assessed EA in patients less than 18 years old who underwent general anesthesia. We excluded studies that did not use a specific evaluation to assess EA. RESULTS: Nine studies (951 participants) were included in this systematic review. Melatonin significantly reduced the incidence of EA compared with placebos (risk ratio 0.40, 95% CI 0.26 to 0.61, P < 0.01) and midazolam (risk ratio 0.48, 95% CI 0.32 to 0.73, P < 0.01). Dexmedetomidine remarkably decreased the incidence of EA compared with melatonin (risk ratio 2.04, 95% CI 1.11 to 3.73, P = 0.02). CONCLUSIONS: Melatonin premedication significantly decreases the incidence of EA compared with placebos and midazolam. Dexmedetomidine premedication has a stronger effect than melatonin in preventing EA. Nevertheless, further studies are warranted to reinforce and validate the conclusion on the efficacy of melatonin premedication in mitigating EA in pediatric patients.

Postoperative recovery in preschool-aged children: A secondary analysis of a randomized controlled trial comparing premedication with midazolam, clonidine, and dexmedetomidine.

BACKGROUND: Preoperative anxiety in pediatric patients can worsen postoperative outcomes and delay discharge. Drugs aimed at reducing preoperative anxiety and facilitating postoperative recovery are available; however, their effects on postoperative recovery from propofol-remifentanil anesthesia have not been studied in preschool-aged children. Thus, we aimed to investigate the effects of three sedative premedications on postoperative recovery from total intravenous anesthesia in children aged 2-6 years. METHODS: In this prespecified secondary analysis of a double-blinded randomized trial, 90 children scheduled for ear, nose, and throat surgery were randomized (1:1:1) to receive sedative premedication: oral midazolam 0.5 mg/kg, oral clonidine 4 µg/kg, or intranasal dexmedetomidine 2 µg/kg. Using validated instruments, outcome measures including time for readiness to discharge from the postoperative care unit, postoperative sedation, emergence delirium, anxiety, pain, and nausea/vomiting were measured. RESULTS: After excluding eight children due to drug refusal or deviation from the protocol, 82 children were included in this study. No differences were found between the groups in terms of median time [interquartile range] to readiness for discharge (midazolam, 90 min [48]; clonidine, 80 min [46]; dexmedetomidine 100.5 min [42]). Compared to the midazolam group, logistic regression with a mixed model and repeated measures approach found no differences in sedation, less emergence delirium, and less pain in the dexmedetomidine group, and less anxiety in both clonidine and dexmedetomidine groups. CONCLUSIONS: No statistical difference was observed in the postoperative recovery times between the premedication regimens. Compared with midazolam, dexmedetomidine was favorable in reducing both emergence delirium and pain in the postoperative care unit, and both clonidine and dexmedetomidine reduced anxiety in the postoperative care unit. Our results indicated that premedication with α2 -agonists had a better recovery profile than short-acting benzodiazepines; although the overall recovery time in the postoperative care unit was not affected.