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Objectives: To compare the efficacy and safety of sedation with midazolam and remimazolam for colorectal endoscopy. Methods: This single-center, two-arm, post-hoc analysis of the REM-IICTJP01 study investigated the efficacy and safety of remimazolam for gastrointestinal endoscopic sedation. We enrolled 40 and 208 patients who underwent colonoscopy under remimazolam and midazolam sedation, respectively, during the same period. The primary outcome was the time from the end of the colonoscopy until discharge. The secondary outcomes included the time from the end of the colonoscopy until awakening, dosage, and adverse events. Propensity score matching was employed to eliminate the effect of confounding factors. Results: Thirty-seven patients in each group were matched. After propensity matching, the time to awakening after colonoscopy was 28.0 (13.0-37.0) min in the midazolam group and 0 (0-0) min in the remimazolam group; moreover, the time till discharge was 40.0 (35.0-46.5) min in the midazolam group and 0 (0-5.0) min in the remimazolam group, both of which were significantly shorter in the remimazolam group (p < 0.01). The number of additional doses was 0 (0-0) and 2 (1-3) in the midazolam and remimazolam groups, respectively. The total dose was 2.0 (2.0-3.5) and 6.0 (5.0-7.0) mg in the midazolam and remimazolam groups, respectively. Conclusions: Remimazolam yielded significantly faster times to awakening and discharge safely compared to midazolam.

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Objectives: The effectiveness and safety of propofol-based sedation and midazolam sedation in pediatric bidirectional endoscopy were compared. Methods: We retrospectively analyzed the cases of pediatric patients (≤15 years old) who had undergone bidirectional endoscopy, esophagogastroduodenoscopy, and colonoscopy by pediatric gastroenterologists. Demographic data, indications, sedatives/dosages, clinical outcomes, endoscopic findings, adverse events, and total patient time requirements (total time in which patients stay in our hospital) were compared in the two sedation groups. Results: Ninety-one children (51 boys, 40 girls, mean age 13 years, range 9-15) treated at our hospital were enrolled. Propofol alone or in combination with midazolam and/or pentazocine was administered to 51 patients (propofol-based sedation group). Midazolam alone or in combination with pentazocine was administered to the other 40 patients (midazolam sedation group). In the propofol group, the following mean doses were used: propofol, 96 mg (range 40-145 mg); midazolam, 4.9 mg (range 3-5 mg); and pentazocine, 7.5 mg. In the midazolam group, the mean doses of midazolam and pentazocine were 6.2 mg (range 4-10 mg) and 15 mg, respectively. All procedures were successfully completed by pediatric gastroenterologists. The total procedure times and endoscopic findings were similar in the two groups, but the median patient time requirement in the propofol group was significantly shorter versus the midazolam group (7.3 h vs. 8.4 h, p < 0.001). No adverse events occurred in either group. Conclusions: Propofol-based sedation in pediatric bidirectional endoscopy was safely and effectively performed by pediatric gastroenterologists, and its patient time requirement was shorter than that for midazolam sedation.

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Background/Objectives: Neuromuscular blocking agents (NMBAs) are not usually necessary during the induction of general anesthesia in patients using supraglottic airway (SGA) devices. In this study, we assessed the incidences of rocuronium use in adult patients undergoing general anesthesia using SGA devices. Methods: From September 2022 to August 2023, the medical records of adult patients (≥19 years) who underwent orthopedic surgery using SGA devices were retrospectively investigated. The incidences of rocuronium use during anesthetic induction were analyzed according to the anesthetic induction drug. The association of rocuronium use during anesthesia was analyzed in terms of demographic (age, sex, height, and weight), surgical (surgical time), and anesthetic factors (premedication, anesthetic agent, anesthetic time). Results: In total, 321 patients were enrolled. The incidence rate of rocuronium use during anesthetic induction was 28.3%. In the subgroup analysis, patients receiving total intravenous anesthesia (TIVA) with propofol (PPF) and remifentanil showed a markedly lower incidence (14.4%) than the other anesthetic groups. Premedication or short anesthetic duration was associated with lower incidences of rocuronium use. Demographic and other anesthetic factors did not seem to affect the incidences of rocuronium use during anesthesia. Conclusions: The incidence of rocuronium use during anesthetic induction with SGA devices was significantly lower with the PPF-TIVA compared to that using remimazolam-TIVA or inhalational anesthesia. Premedication with midazolam and shorter operation times were associated with a significantly lower incidence of rocuronium use.

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BACKGROUND: Sedation at the end of life is used to relieve distressing symptoms including agitation and delirium. Standard care may include infused benzodiazepines or antipsychotics. These agents often result in deep sedation with loss of interaction with loved ones, which may be distressing. OBJECTIVE: The DREAMS (Dexmedetomidine for the Reduction of End-of-life Agitation and for optiMised Sedation) trial aimed to compare the sedative and antidelirium effects of the alpha-2 agonist dexmedetomidine, a novel palliative care sedative, compared with midazolam, a benzodiazepine when administered by subcutaneous infusion at the end of life, with doses of both agents targeting lighter, or potentially interactive sedation. METHODS: Participants were recruited from adult inpatients admitted for end-of-life care under a palliative care team in regional New South Wales, Australia. Inclusion criteria included patients older than 18 years, with a preference for lighter sedation at the end of life. Exclusion criteria included severe cardiac dysfunction (contraindication to dexmedetomidine). Participants consented and were placed on a treatment-pending list. Upon experiencing terminal deterioration, patients were randomized to either arm 1 (dexmedetomidine) or arm 2 (midazolam) as their treatment arm. These treatments were administered by continuous subcutaneous infusion. The level of consciousness and agitation of the patients were measured by the Richmond Agitation-Sedation Scale-Palliative version and the Memorial Delirium Assessment Score. Richmond Agitation-Sedation Scale-Palliative version assessments were performed by both nursing and medical staff, while Memorial Delirium Assessment Score assessments were carried out by medical staff only. Families and patients were asked to complete, as able, a patient comfort assessment form, to gauge perceptions of distress. Data were collected and matched with the breakthrough medication doses administered, along with qualitative comments in the medical record. In addition, the study tracked symptoms and patient functional status that were recorded as part of the Palliative Care Outcomes Collaborative, a national tracking project for monitoring symptom outcomes in palliative care. RESULTS: The DREAMS trial was funded in May 2020, approved by the ethics committee in November 2020, and started recruiting participants in May 2021. Data collection commenced in May 2021 and is anticipated to continue until December 2024. Publication of results is anticipated from 2024 to 2026. CONCLUSIONS: The evidence base for sedative dosing in palliative care for distress and agitation is not robust, with standard care based primarily on clinical experience and not robust scientific evidence. This study is important because it will compare a standard and a novel sedative used in end-of-life treatment. By assessing the potential efficacy and benefits of both, it seeks to optimize the quality of dying by providing targeted sedation that can improve the communication between dying patients and their loved ones. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Register ACTRN12621000052831; https://uat.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=380889. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55129.

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An intravenous (IV) administration of midazolam may result in seizure-like activity or movement. This report describes 5 neonates who developed seizure-like movements after IV midazolam injection. The patients presented between 2019 and 2022 and were admitted to a neonatal intensive care unit located within an academic centre in Muscat, Oman. The abnormal movements occurred shortly after IV bolus administration of midazolam. None of the patients experienced seizure-like movements after receiving midazolam infusions. The seizure-like movements were aborted either spontaneously or by antiseizure medications. In addition, seizure recurrence was not observed in any of the infants during the later stages of their treatment. Since this adverse effect might be related to the speed of the bolus administration, IV midazolam must be given as a slow bolus over 2-3 minutes followed by a slow flush of normal saline. To prevent midazolam's potential adverse effect on newborns, neonatal caregivers must be aware of it.

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Aneurysmal subarachnoid hemorrhage (aSAH) is characterized by high mortality and morbidity. This scoping review assesses the current evidence regarding the use of sedatives and analgesics in the acute intensive care unit management of aSAH. We conducted a systematic search of Ovid MEDLINE, Ovid Embase, Ovid EmCare, APA PsycInfo, CINAHL, and the Cochrane Database of Systematic Reviews from inception to June 2023. Studies were included if they enrolled intensive care unit patients aged 18 or older with a significant proportion (> 20%) who had aSAH and evaluated the impact of one or more commonly used analgosedatives on physiological parameters in the management of aSAH. The methodological quality of the studies was assessed using the Methodological Index for Nonrandomized Studies score. Of 2,583 articles, 11 met the inclusion criteria. The median sample size was 47 (interquartile range 10-127), and the median Methodological Index for Nonrandomized Studies score was 9.5 (interquartile range 8-11). The studies' publication years ranged from 1980 to 2023. Dexmedetomidine and ketamine showed potential benefits in reducing the incidence of cortical spreading depolarization and delayed cerebral ischemia. Propofol and opioids appeared safe but lacked robust evidence for efficacy. Benzodiazepines were associated with increased delayed cerebral ischemia-related cerebral infarctions and cortical spreading depolarization events. The evidence available to guide the use of analgosedative medications in aSAH is critically inadequate. Dexmedetomidine and ketamine warrant further exploration in large-scale prospective studies because of their potential benefits. Improved study designs with consistent definitions and a focus on patient-centered outcomes are necessary to inform clinical practice.

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Background Painful procedures in the pediatric emergency department often require the use of sedation and analgesia to ensure adequate pain control, a right of children and adolescents. This study aims to describe the procedural sedation and analgesia with intravenous medications performed in a pediatric emergency department. Methods This is a retrospective descriptive study of intravenous sedoanalgesia used in a pediatric emergency department of a level II district hospital in the Lisbon metropolitan area from October 2018 to December 2023. The type of intervention, drugs used, and adverse events were analyzed. Results A total of 615 patients were included in the study; 65.7% (n=404) were male with a median age of 6 years. The most frequently performed procedures were wound suturing (50.9%, n=313) and fracture reduction (36.3%, n=223). The drugs used for sedation and analgesia were ketamine (99.2%, n=610), midazolam (95.8%, n=589), propofol (1.6%, n=10), and morphine (0.5%, n=3). The majority of patients received midazolam and ketamine in association (93.8%, n=577). A total of 50 adverse events (8.1%) were recorded in 42 patients. The most frequent side effects were transient oxygen desaturation (2%, n=12), vomiting (1.5%, n=9), apnea/bradypnea (1%, n=6), and hallucinations (0.8%, n=5). The occurrence of adverse events was not dose-dependent (p >0.05). Respiratory complications resolved without requiring invasive interventions. Children were sedated by a pediatric intensivist in 68.1% (n=419), by a general pediatrician in 26.7% (n=164), and by a pediatric resident in 2% (n=12). Conclusions The results of this study demonstrate that intravenous sedoanalgesia, particularly the combination of ketamine and midazolam, is a safe method for sedation in pediatric patients, with a low rate of adverse events.

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Palliative sedation aims to relieve refractory suffering in patients with life-limiting disease. The 2009 framework on palliative sedation of the European Association for Palliative Care (EAPC) has recently been updated. Recommendations have also been formulated by the research group SedPall in Germany. This article describes the social and ethical complexity of decision-making and summarises the recommendations. Patient autonomy is emphasised. Refractoriness of the suffering should be determined jointly by physician and patient. Sedation should be proportional, that is to say, its form and duration should be adapted to the patient's individual situation. The decision on palliative sedation and that on hydration involve two separate decision-making processes. Midazolam should be used as first choice. Particular attention should be paid to the patient's relatives/significant others and the treating team.

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BACKGROUND: Fear and anxiet are significant barriers of dental care in children. Sedation emerged as a valuable behaviour guidance technique to manage uncooperative children. AIM: To evaluate the sedative and behavioral effectiveness of midazolam administered via nebulizer in comparison with intranasal atomizer in the behavior management of anxious children during dental treatment. STUDY DESIGN: Two-arm randomized clinical trial with 68 children (3-5 years) assigned to receive nebulized midazolam (NEB MDZ) and atomized intranasal midazolam (AIN MDZ) during dental treatment. The onset time, sedation levels, and behavior of children were documented. The data were analyzed using the Wilcoxon signed-rank test and Mann-Whitney U tests. RESULTS: Significant differences between the two groups in terms of onset time, sedation level, and behavior of children during the dental treatment. AIN MDZ was associated with a significantly faster onset time compared with NEB MD, (p < .001). Children who received NEB MDZ exhibited deeper levels of sedation compared with AIN MDZ group (p = .02). During the administration of local anesthesia, notable statistical differences were observed between the behavior of the two groups (p = .02). CONCLUSIONS: Midazolam administered via either nebulizer or intranasal atomizer was the effective route of administration and proved effective in the management of anxious children undergoing dental treatment. AIN MDZ, however, exhibited a faster onset time, whereas children receiving NEB MDZ demonstrated superior behavior compared with those receiving AIN MDZ.

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Background Propofol and midazolam are the most common sedative agents used in critical settings. Propofol and midazolam might have different mortality rates after sedation administration. Some studies mention that propofol is associated with a lower mortality rate than midazolam in mechanically ventilated patients, but other studies have contradicting results. This study aims to compare the 28-day mortality of propofol versus midazolam for patients undergoing mechanical ventilation in the National Guard Hospital Health Affairs (NGHA)-Western Region (WR). Methods A retrospective chart review was conducted at (NGHA-WR) from March 2016 to July 2022. The inclusion criteria were those mechanically ventilated patients aged 18 years or older who were admitted to ICU, where they were given either propofol or midazolam as the initial sedative agent. Those who signed DNR (Do Not Resuscitate) or were contraindicated to sedation, such as allergy, were excluded from the study. Data were retrospectively retrieved and obtained from the Hospital Information System (HIS-BestCare, Saudi-Korean Health Informatics Company, Riyadh, Saudi Arabia) and the Office of Data Intelligence. Results There is a significant difference between the type of sedation and the 28-day mortality rate. Midazolam was associated with higher rates of mortality - 104 (47.93%) when compared to propofol - three (14.29%). Also, patients who used midazolam had longer durations of ICU stay compared to propofol, with a mean number of 19.23 days vs 7.55 days, respectively. Conclusion There is a significant difference regarding the 28-day mortality between patients who were given propofol or midazolam as an initial sedative agent for mechanical ventilation ≥ 24 hours. Moreover, the use of propofol is associated with fewer days of being intubated or being in ICU when compared to midazolam.

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Background: This prospective, randomized, double-blind trial was done to compare intranasal dexmedetomidine and intranasal midazolam as premedication for sedation and ease of child-parent separation in pediatric patients of tetralogy of Fallot (TOF) undergoing corrective cardiac surgery. Materials and Methods: Forty children with TOF, between 1 and 10 years, undergoing corrective cardiac surgery were included in the study and, after randomization, were given intranasal midazolam (0.2 mg/kg) or intranasal dexmedetomidine (1 µg/kg), 30 min before shifting to the operation room (OR). Patients were assessed for sedation and child-parent separation, along with hemodynamic parameters, respiratory rate, and oxygen saturation (SpO2) 30 min after drug administration, at the time of shifting inside the OR, and at the time of induction of anesthesia. Results: Both groups had comparable child-parent scores, hemodynamic parameters, SpO2, and respiratory rate. However, the dexmedetomidine group had significantly better sedation levels than the midazolam group patients at the time of shifting inside the OR (dexmedetomidine group: 3.55 ± 0.82 vs. midazolam group: 2.80 ± 0.83; P = 0.007) and at the time of induction of anesthesia (dexmedetomidine group: 3.40 ± 0.75 vs. midazolam group: 2.70 ± 0.86; P = 0.009). Conclusion: Intranasal dexmedetomidine provides better sedation than midazolam, with similar child-parent separation scores and hemodynamic parameters, respiratory rate, and SpO2. No adverse events were observed in both groups. A study on a larger population will help in further establishing the safety and superiority of dexmedetomidine and will further its regular use as an intranasal premedication.

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Background and objectives Spinal anesthesia stands as a cornerstone for patients undergoing lower segment cesarean section (LSCS), offering advantages like faster onset and high block density. Levobupivacaine, known for its high potency and long-acting nature, has a slower onset. The safety of intrathecal fentanyl or midazolam is evaluated as an adjuvant to levobupivacaine in parturients. This study aims to compare the duration of postoperative analgesia provided by fentanyl or midazolam added to 0.5% hyperbaric levobupivacaine in elective cesarean sections. Secondary objectives include evaluating the onset and duration of sensory and motor blockade and the incidence of nausea and vomiting. Identifying the more effective adjuvant will help optimize spinal anesthesia protocols, improve postoperative outcomes, and enhance patient comfort and recovery. Methods This study was conducted at SRM Medical College Hospital and Research Centre, Chennai, India, over six months (May 1, 2023, to October 1, 2023). A total of 90 patients undergoing elective LSCS received spinal anesthesia in a prospective randomized double-blinded controlled trial. Patients were allocated to three groups: Group A received levobupivacaine with fentanyl, Group B received levobupivacaine with midazolam, and Group C received levobupivacaine with normal saline. Block characteristics, postoperative analgesia, hemodynamic stability, and complications were assessed. Assessments were conducted at specified time points: intraoperatively, every five minutes for the first 30 minutes, every 10 minutes for the next hour, every two hours for six hours, and every four hours up to 24 hours postoperatively. Statistical analysis utilized one-way analysis of variance (ANOVA). Results Group B (levobupivacaine with midazolam) exhibited a shorter time to sensory block onset (88 seconds) compared to Groups A and C (both 145 seconds) (p < 0.001). Group A (levobupivacaine with fentanyl) showed a shorter time to maximum motor block (p = 0.045) than Groups B and C. The sensory block duration was significantly longer in Group A (127.5 minutes) compared to Group B (60 minutes) and Group C (69 minutes) (p < 0.001). Motor block duration was also prolonged in Group A (251 minutes) compared to Group B (147 minutes) and Group C (177 minutes) (p = 0.045). The first analgesic requirement was delayed in Group A (248 minutes), whereas Groups B (115 minutes) and C (90 minutes) (p < 0.001) required more frequent analgesia. Group A experienced a higher incidence of postoperative nausea and vomiting. Conclusion Midazolam accelerated sensory block onset, while fentanyl prolonged anesthesia duration without significantly affecting motor block. Fentanyl delayed the first analgesic requirement, whereas midazolam reduced postoperative nausea, vomiting, and shivering.

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BACKGROUND: Midazolam (MZ) is commonly used in critically ill neurosurgical patients. Neuro-penetration of MZ and its metabolite, 1-hydroxy-midazolam (1-OH-MZ), is not well characterized. OBJECTIVE: This study evaluated correlations between serum and cerebrospinal fluid (CSF) concentrations of MZ and 1-OH-MZ and assessed implications on patient sedation. METHODS: Adults in the neurosurgical intensive care unit (ICU) with external ventricular drains receiving MZ via continuous infusion were prospectively studied. Serum and CSF samples were obtained 12-24 h and 72-96 h after initiation, and concentrations were determined in duplicate by high-performance liquid chromatography with tandem mass spectrometry. Bivariate correlation analyses used Pearson coefficient. RESULTS: A total of 31 serum and CSF samples were obtained from 18 subjects. At sampling, mean MZ infusion rate was 3.9 ± 4.4 mg/h, and previous 12-h cumulative dose was 51.4 ± 78.2 mg. Mean concentrations of MZ and 1-OH-MZ in serum and CSF were similar between timepoints. Similarly, ratios of 1-OH-MZ to MZ in serum and CSF remained stable over time. Serum MZ (126.2 ± 89.3 ng/mL) showed moderate correlation (r2 = 0.68, P < 0.001) with serum 1-OH-MZ (17.7 ± 17.6 ng/mL) but not CSF MZ (3.9 ± 2.5 ng/mL; r2 = 0.24, P = 0.005) or CSF 1-OH-MZ (2.5 ± 0.6 ng/mL; r2 = 0.47, P = 0.30). CSF MZ did not correlate with CSF 1-OH-MZ (r2 = 0.003, P < 0.001). Mean serum ratio of 1-OH-MZ to MZ (0.14 ± 0.2 ng/mL) did not correlate with CSF ratio (1.06 ± 0.83 ng/mL; r2 = 0.06, P = 0.19). Concentrations and ratios were unrelated to MZ infusion rate or 12-h cumulative dose. Sedation was weakly correlated with CSF 1-OH-MZ, but not with serum MZ, serum 1-OH-MZ, or CSF MZ. CONCLUSION AND RELEVANCE: Continuous infusions of MZ result in measurable concentrations of MZ and 1-OH-MZ in CSF; however, CSF concentrations of MZ and 1-OH-MZ poorly represent serum concentrations or dosages. Accumulation of MZ and 1-OH-MZ in serum or CSF over time was not evident. Concentrations of MZ and 1-OH-MZ do not predict sedation levels, reinforcing that pharmacodynamic assessments are warranted.

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The triggers of status epilepticus (SE) in non-epileptic patients can vary widely, from idiopathic causes to exposure to chemoconvulsants. Regardless of its etiology, prolonged SE can cause significant brain damage, commonly resulting in the development of epilepsy, which is often accompanied by increased anxiety. GABAA receptor (GABAAR)-mediated inhibition has a central role among the mechanisms underlying brain damage and the ensuing epilepsy and anxiety. During SE, calcium influx primarily via ionotropic glutamate receptors activates signaling cascades which trigger a rapid internalization of synaptic GABAARs; this weakens inhibition, exacerbating seizures and excitotoxicity. GABAergic interneurons are more susceptible to excitotoxic death than principal neurons. During the latent period of epileptogenesis, the aberrant reorganization in synaptic interactions that follow interneuronal loss in injured brain regions, leads to the formation of hyperexcitable, seizurogenic neuronal circuits, along with disturbances in brain oscillatory rhythms. Reduction in the spontaneous, rhythmic "bursts" of IPSCs in basolateral amygdala neurons is likely to play a central role in anxiogenesis. Protecting interneurons during SE is key to preventing both epilepsy and anxiety. Antiglutamatergic treatments, including antagonism of calcium-permeable AMPA receptors, can be expected to control seizures and reduce excitotoxicity not only by directly suppressing hyperexcitation, but also by counteracting the internalization of synaptic GABAARs. Benzodiazepines, as delayed treatment of SE, have low efficacy due to the reduction and dispersion of their targets (the synaptic GABAARs), but also because themselves contribute to further reduction of available GABAARs at the synapse; furthermore, benzodiazepines may be completely ineffective in the immature brain.

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AIM: Management of primary healthcare and routine minor procedures for children with autism spectrum disorder (ASD) can be challenging; therefore, when behavioural strategies fail, sedative medications are often employed. We evaluated the effectiveness of the current pharmacological strategies for managing children with ASD. METHODS: We performed a systematic review and meta-analysis of the current approaches for procedural sedation in children with ASD. RESULTS: Twenty studies met inclusion criteria. Dexmedetomidine, midazolam, propofol and chloral hydrate were the most efficient agents for successful procedures, while propofol had the highest number of adverse events. The most frequently used agents were dexmedetomidine and midazolam or a combination of the two, and the effectiveness of dexmedetomidine plus midazolam was superior to dexmedetomidine alone. CONCLUSION: Multiple effective drug regimens exist for procedural sedation in children with ASD. These results could support the development of specific guidelines for procedural sedation in children with ASD.

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Aims and background: In postoperative patients in the intensive care units (ICUs), not only analgesics are needed but also sedation so that the patient can remain calm during treatment, especially patients with mechanical ventilation. By using the measurement parameters of the quantum consciousness index (qCON) and quantum noxious index (qNOX) in measuring the depth of sedation and adequacy of analgesics, the use of subdose ketamine instead of fentanyl and midazolam as sedative, analgesic agents can be performed as a new alternative to nociceptive monitoring methods with more objective results. This study aims to obtain results of comparing qCON and qNOX in postoperative patients by administering subdose ketamine compared with a combination of fentanyl and midazolam in RSUP Haji Adam Malik Medan. Materials and methods: A randomized clinical trial with a double-blind approach has been used in this study. A total of 44 experimental samples were gathered and randomly split into two groups after meeting the criteria for inclusion. Group A administered a ketamine subdose, whereas Group B administered a mixture of fentanyl and midazolam. The research data obtained were tested using Statistical Product and Science Service (SPSS). Results: There were differences in the median, minimum, and maximum values of qCON and qNOX in the groups given subdose ketamine and fentanyl and midazolam, but these were not statistically significant (p > 0.05) at T0, T1, and T2. Conclusion: Administering a subdose of ketamine can provide sedation and analgesia comparable to fentanyl and midazolam. How to cite this article: Masharto AR, Lubis AP, Bangun CG, Wahyuni AS. Quantium Consciousness Index and Quantium Noxious Index in Ketamine Subdose Administration Compared with Fentanyl and Midazolam in Postoperative ICU Patients: A Prospective, Observational Study. Indian J Crit Care Med 2024;28(6):581-586.

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Objectives: Newborns and small infants are unable to cooperate actively during diagnostic procedures; therefore, sedation is often employee to maintain immobilization and obtain high-quality images. However, these procedures are often indicated in sick, vulnerable, or hemodynamically unstable neonates and young infants, which raises the associated risks of sedation. This study summarizes our 4-year of experience with safe and effective procedural sedation in this vulnerable population. Study design: This retrospective study analyzed data on neonates and young infants who underwent non-painful diagnostic procedures from December 2019 to November 2023. Patients were categorized into the neonate (aged≦ 28 days) and the young infant (29 days ≦ aged ≦ 90 days) groups. Results: Non-pharmacological strategies, including sleeping naturally, swaddling/facilitated tucking, non-nutritive sucking, and skin-to-skin care, can achieve a success rate for sedation about 98.4%. In terms of pharmacological methods, our institution primarily utilizes chloral hydrate for procedural sedation in neonates and young infants undergoing non-painful diagnostic procedures. Midazolam serves as an alternative sedative. Chloral hydrate alone demonstrated a 92.5% success rate on the first attempt, compared to midazolam alone, with an 85.11% success rate. Neonates experienced a higher incidence of adverse events during sedation compared to young infants. Conclusion: This study reviews our 4-year experience with procedural sedation in neonates and young infants. Chloral hydrate demonstrated a high degree of safety and efficacy in this population. However, supervision by skilled medical personnel and extended observation is required. In our institution, the experience with midazolam is limited in this population, and further research is warranted to establish its safety and efficacy. Non-pharmacological strategies can achieve an acceptable rate of sedation success, which can be used based on patient's tolerance.

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Purpose: Anxiety and depression can affect the physiology of the gastrointestinal tract through the brain-gut axis, causing gastrointestinal dysfunction, which is mainly manifested as indigestion, diarrhoea, constipation, or abdominal pain. Preoperative anxiety arises in children due to separation from parents, fear of unfamiliar surroundings and anaesthesia and surgical procedures.To discuss the effect of alleviating preoperative anxiety on postoperative recovery of gastrointestinal function in children with indirect inguinal hernia after laparoscopic high ligation of the hernia sac. Patients and Methods: 90 children with laparoscopic high ligation of the herniated sac in oblique inguinal hernia were randomly divided into control group (Group C) and experimental group (Group M). The Group M was given midazolam oral solution 0.5mg/kg (maximum dose 20mg), and The Group C was given 5% glucose solution with the same dose.Primary outcome was the time to first postoperative defecation and I-FEED scores.The secondary outcomes included mYPAS-SF scores; child sedation scores; child-parent separation scores; parental STAI scores;PHBQ scores;FLACC scores, operative time, and fluid input and surgeon job satisfaction. Results: Compared with Group C, there was a shorter time to first postoperative defecation (P < 0.05), and lower I-FEED scores on postoperative day 1 (P < 0.05). The mYPAS-SF scores, which were significantly different in Group M at T1, T2, and T3 (P < 0.05), parental STAI scores at S1, child sedation scores and child-parent separation scores in T1, and surgeon job satisfaction between the two groups were significantly different (P < 0.05). There were no statistically significant differences in I-FEED scores on days 2 and 3, PHBQ scores, FLACC scores, operative time, and fluid input between the two groups of children (P > 0.05). Conclusion: Preoperative application of midazolam oral solution to relieve preoperative anxiety helps to promote the recovery of postoperative gastrointestinal function in children with indirect inguinal hernia and increases the surgeon job satisfaction.

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Recent advances in genetic diagnosis identified variants in genes encoding GABAA receptors as causative for genetic epilepsy. Here, we selected eight disease-associated variants in the α1 subunit of GABAA receptors causing mild to severe clinical phenotypes and showed that they are loss of function, mainly by reducing the folding and surface trafficking of the α1 protein. Furthermore, we sought client protein-specific pharmacological chaperones to restore the function of pathogenic receptors. Applications of positive allosteric modulators, including Hispidulin and TP003, increase the functional surface expression of the α1 variants. Mechanism of action study demonstrated that they enhance the folding, assembly, and trafficking and reduce the degradation of GABAA variants without activating the unfolded protein response in HEK293T cells and human iPSC-derived neurons. Since these compounds cross the blood-brain barrier, such a pharmacological chaperoning strategy holds great promise to treat genetic epilepsy in a GABAA receptor-specific manner.