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PloS One 2023Therapeutic hypothermia (TH) is a widely practiced neuroprotective strategy for neonates with hypoxic-ischemic encephalopathy. Induced hypothermia is associated with... (Review)
Review
BACKGROUND
Therapeutic hypothermia (TH) is a widely practiced neuroprotective strategy for neonates with hypoxic-ischemic encephalopathy. Induced hypothermia is associated with shivering, cold pain, agitation, and distress.
OBJECTIVE
This scoping review determines the breadth of research undertaken for pain and stress management in neonates undergoing hypothermia therapy, the pharmacokinetics of analgesic and sedative medications during hypothermia and the effect of such medication on short- and long-term neurological outcomes.
METHODS
We searched the following online databases namely, (i) MEDLINE, (ii) Web of Science, (iii) Cochrane Library, (iv) Scopus, (v) CINAHL, and (vi) EMBASE to identify published original articles between January 2005 and December 2022. We included only English full-text articles on neonates treated with TH and reported the sedation/analgesia strategy used. We excluded articles that reported TH on transport or extracorporeal membrane oxygenation, did not report the intervention strategies for sedation/analgesia, and reported hypoxic-ischemic encephalopathy in which hypothermia was not applied.
RESULTS
The eligible publications (n = 97) included cohort studies (n = 72), non-randomized experimental studies (n = 2), pharmacokinetic studies (n = 4), dose escalation feasibility trial (n = 1), cross-sectional surveys (n = 5), and randomized control trials (n = 13). Neonatal Pain, Agitation, and Sedation Scale (NPASS) is the most frequently used pain assessment tool in this cohort. The most frequently used pharmacological agents are opioids (Morphine, Fentanyl), benzodiazepine (Midazolam) and Alpha2 agonists (Dexmedetomidine). The proportion of neonates receiving routine sedation-analgesia during TH is center-specific and varies from 40-100% worldwide. TH alters most drugs' metabolic rate and clearance, except for Midazolam. Dexmedetomidine has additional benefits of thermal tolerance, neuroprotection, faster recovery, and less likelihood of seizures. There is a wide inter-individual variability in serum drug levels due to the impact of temperature, end-organ dysfunction, postnatal age, and body weight on drug metabolism.
CONCLUSIONS
No multidimensional pain scale has been tested for reliability and construct validity in hypothermic encephalopathic neonates. There is an increasing trend towards using routine sedation/analgesia during TH worldwide. Wide variability in the type of medication used, administration (bolus versus infusion), and dose ranges used emphasizes the urgent need for standardized practice recommendations and guidelines. There is insufficient data on the long-term neurological outcomes of exposure to these medications, adjusted for underlying brain injury and severity of encephalopathy. Future studies will need to develop framework tools to enable precise control of sedation/analgesia drug exposure customized to individual patient needs.
Topics: Infant, Newborn; Humans; Midazolam; Dexmedetomidine; Cross-Sectional Studies; Hypoxia-Ischemia, Brain; Hypothermia; Reproducibility of Results; Pain; Analgesia; Hypothermia, Induced
PubMed: 38060481
DOI: 10.1371/journal.pone.0291170 -
Journal of the American Medical... Aug 2023To describe acute seizure treatment for the long-term care setting, emphasizing rescue (acute abortive) medications for on-site management of acute unexpected seizures... (Review)
Review
OBJECTIVES
To describe acute seizure treatment for the long-term care setting, emphasizing rescue (acute abortive) medications for on-site management of acute unexpected seizures and seizure clusters.
DESIGN
Narrative review.
SETTING AND PARTICIPANTS
People with seizures in long-term care, including group residences.
METHODS
PubMed was searched using keywords that pertained to rescue medications, seizure emergencies/epilepsy, seizure action plans, and long-term care.
RESULTS
Seizure disorder, including epilepsy, is prevalent in long-term care residences, and rescue medications can be used for on-site treatment. Diazepam rectal gel, intranasal midazolam, and diazepam nasal spray are US Food and Drug Administration (FDA)-approved seizure-cluster rescue medications, and intravenous diazepam and lorazepam are approved for status epilepticus. Benzodiazepines differ by formulation, route of administration, absorption, and metabolism. Intranasal formulations are easy and ideal for public use and when rectal treatment is challenging (eg, wheelchair). Intranasal, intrabuccal, and rectal formulations do not require specialized training to administer and are easier for staff at all levels of training compared with intravenous treatment. Off-label rescue medications may have anecdotal support; however, potential disadvantages include variable absorption and onset of action as well as potential risks to patients and caregivers or care partners. Delivery of intravenous-administered rescue medications is delayed by the time needed to set up and deliver the medication and is subject to dosing errors. Seizure action plans that include management of acute seizures can optimize the quality and timing of treatment, which may reduce emergency service needs and prevent progression to status epilepticus.
CONCLUSIONS AND IMPLICATIONS
Seizure disorder is prevalent across all ages but is increased in older adults and in those with intellectual and developmental disabilities. Prompt intervention may reduce negative outcomes associated with acute unexpected seizures and seizure clusters. Seizure action plans that include acute seizures can improve the treatment response by detailing the necessary information for staff to provide immediate treatment.
Topics: United States; Humans; Aged; Anticonvulsants; Long-Term Care; Diazepam; Status Epilepticus; Epilepsy
PubMed: 37253432
DOI: 10.1016/j.jamda.2023.04.015 -
Neuropsychopharmacology : Official... Oct 2023NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a... (Randomized Controlled Trial)
Randomized Controlled Trial
NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be reconsolidated in an altered form. This concept might have significant clinical implications in treating PTSD. In this pilot study we tested the potential of a single infusion of ketamine, followed by brief exposure therapy, to enhance post-retrieval extinction of PTSD trauma memories. 27 individuals diagnosed with PTSD were randomly assigned to receive either ketamine (0.5 mg/kg 40 min; N = 14) or midazolam (0.045 mg/kg; N = 13) after retrieval of the traumatic memory. 24 h following infusion, participants received a four-day trauma-focused psychotherapy. Symptoms and brain activity were assessed before treatment, at the end of treatment, and at 30-day follow-up. Amygdala activation to trauma scripts (a major biomarker of fear response) served as the main study outcome. Although PTSD symptoms improved equally in both groups, post-treatment, ketamine recipients showed a lower amygdala (-0.33, sd = 0.13, 95%HDI [-0.56,-0.04]) and hippocampus (-0.3 (sd = 0.19), 95%HDI [-0.65, 0.04]; marginal effect) reactivation to trauma memories, compared to midazolam recipients. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus (-0.28, sd = 0.11, 95%HDI [-0.46, -0.11]), with no change in amygdala-vmPFC connectivity. Moreover, reduction in fractional anisotropy in bi-lateral uncinate fasciculus was seen in the Ketamine recipients compared with the midazolam recipients (right: post-treatment: -0.01108, 95% HDI [-0.0184,-0.003]; follow-up: -0.0183, 95% HDI [-0.02719,-0.0107]; left: post-treatment: -0.019, 95% HDI [-0.028,-0.011]; follow-up: -0.017, 95% HDI [-0.026,-0.007]). Taken together it is possible that ketamine may enhance post-retrieval extinction of the original trauma memories in humans. These preliminary findings show promising direction toward the capacity to rewrite human traumatic memories and modulate the fear response for at least 30 days post-extinction. When combined with psychotherapy for PTSD, further investigation of ketamine dose, timing of administration, and frequency of administration, is warranted.
Topics: Humans; Extinction, Psychological; Ketamine; Midazolam; Pilot Projects; Psychotherapy; Stress Disorders, Post-Traumatic
PubMed: 37270621
DOI: 10.1038/s41386-023-01606-3 -
Frontiers in Pediatrics 2023To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis. (Review)
Review
OBJECTIVE
To compare the effects of intranasal dexmedetomidine (Dex) and oral midazolam in the preoperative medication of children by using a method of meta-analysis.
METHODS
Cochrane Library, Pubmed, Embase, and Web of Science were searched from inception to July 2023. Randomized controlled trials (RCTs) of intranasal Dex vs. oral midazolam in pediatric premedication were collected. Stata 15.0 statistical software was used to analyze the collected data. Relative risk (RR) and 95% confidence interval (CI) were used as effect sizes.
RESULTS
A total of 11 studies with 824 children were included, containing 415 patients in the Dex group and 409 patients in the midazolam group. Compared with the oral midazolam group, the intranasal Dex group had a better preoperative sedation effect at parent-child separation (RR = 1.37, 95% CI: 1.14-1.64) and anesthesia induction (RR = 2.08, 95% CI: 1.03-4.22). In addition, there was no significant difference in the incidence of analgesia remedy (RR = 0.60, 95% CI: 0.36-1.00) the acceptance of anesthesia masks (RR = 0.97, 95% CI: 0.83-1.12), and incidence of adverse events between (RR = 0.25, 95% CI: 0.06-1.13, = 0.072) between the intranasal Dex and oral midazolam groups.
CONCLUSION
Compared with oral midazolam, intranasal Dex has better sedative effects of parent-child separation and anesthesia induction in pediatric premedication, but there was no difference in the incidence of anesthesia remedy, anesthesia mask acceptance, and incidence of adverse events. Therefore, compared with oral midazolam, intranasal Dex is a better choice for premedication in children.
PubMed: 38027288
DOI: 10.3389/fped.2023.1264081 -
Wideochirurgia I Inne Techniki... Sep 2023Sedation is common during digestive endoscopy to provide comfort and pain relief for patients. However, the use of sedation in endoscopy also poses potential risks, and... (Review)
Review
Sedation is common during digestive endoscopy to provide comfort and pain relief for patients. However, the use of sedation in endoscopy also poses potential risks, and recent issues have been raised regarding its safety and administration. This literature review paper will discuss the most recent developments in the field of sedation in digestive endoscopy, including the adverse events that might be associated with sedation and how to manage it, the legal issues associated with administration, the impact of COVID-19 on sedation practices, and sedation in special situations. It will also touch upon the current guidelines and recommendations for sedation, including the importance of patient selection and monitoring and the need for training and certification for endoscopists administering sedation. The review will also analyse studies evaluating the safety and efficacy of various sedation techniques, including propofol, midazolam, and others. It will examine the benefits and drawbacks of these agents.
PubMed: 37868289
DOI: 10.5114/wiitm.2023.127854 -
JAMA Network Open Aug 2023Loss of a previously effective response while still using adequate antidepressant treatment occurs in a relatively high proportion of patients with major depressive... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Loss of a previously effective response while still using adequate antidepressant treatment occurs in a relatively high proportion of patients with major depressive disorder (MDD); therefore, there is a need to develop novel effective treatment strategies.
OBJECTIVE
To assess the efficacy and safety of a single subanesthetic dose of esketamine in boosting the efficacy of oral antidepressants for treating fluctuating antidepressant response in MDD.
DESIGN, SETTING, AND PARTICIPANTS
This single-center, double-blind, midazolam-controlled pilot randomized clinical trial was conducted at Beijing Anding Hospital, Capital Medical University in China. The study enrolled participants aged 18 years and older with fluctuating antidepressant response, defined as patients with MDD experiencing fluctuating symptoms after symptom relief and stabilization. Patient recruitment was conducted from August 2021 to January 2022, and participants were followed-up for 6 weeks. Data were analyzed as intention-to-treat from July to September 2022.
INTERVENTIONS
All participants in the esketamine-treated group received intravenous esketamine at 0.2 mg/kg in 40 minutes. Participants in the midazolam control group received intravenous midazolam at 0.045 mg/kg in 40 minutes.
MAIN OUTCOMES AND MEASURES
The primary outcome was the response rate at 2 weeks, defined as a 50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS). Secondary outcomes included response rate at 6 weeks, remission rates at 2 and 6 weeks, and change in MADRS and Clinical Global Impression-Severity score from baseline to 6 weeks; remission was defined by a MADRS score of 10 or lower.
RESULTS
A total of 30 patients (median [IQR] age, 28.0 [24.0-40.0] years; 17 [56.7%] female) were randomized, including 15 patients randomized to midazolam and 15 patients randomized to esketamine; 29 patients completed the study. Response rates at 2 weeks were significantly higher in the esketamine-treated group than in the midazolam control group (10 patients [66.7%] vs 1 patient [6.7%]; P < .001). Participants treated with esketamine experienced significantly greater reduction in MADRS score from baseline to 2 weeks compared with those treated with midazolam (mean [SD] reduction, 15.7 [1.5] vs 3.1 [1.3]; P < .001). No serious adverse events were observed in this trial, and no psychotogenic effects and clinically significant manic symptoms were reported.
CONCLUSIONS AND RELEVANCE
This pilot randomized clinical trial found that a single subanesthetic dose of esketamine could boost the efficacy of oral antidepressants in treating fluctuating antidepressant response, with a good safety profile.
TRIAL REGISTRATION
Chinese Clinical Trial Registry Identifier: ChiCTR2100050335.
Topics: Humans; Female; Adult; Male; Depressive Disorder, Major; Midazolam; Pilot Projects; Antidepressive Agents
PubMed: 37578792
DOI: 10.1001/jamanetworkopen.2023.28817 -
Scientific Reports Nov 2023Although remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety... (Randomized Controlled Trial)
Randomized Controlled Trial
Although remimazolam is an ultra-short-acting benzodiazepine with a shorter elimination half-life and faster recovery time than midazolam, studies evaluating its safety and efficacy during bronchoscopy are limited. This study aimed to compare the safety and efficacy of remimazolam with those of midazolam for bronchoscopy. This prospective randomized parallel-group study was conducted at a single institution. The primary outcome was the time from the end of the procedure to full alertness. Other procedural time parameters, satisfaction profiles, and adverse effects were thoroughly evaluated. The time taken to reach peak sedation and the time from the end of the procedure to full alertness was significantly shorter in the remimazolam group than in the midazolam group (median [interquartile range], 2 min [1-4] vs. 3 min [2-5], P = 0.006; and median, 2 min [1-5] vs. 5 min [1-12], P = 0.035, respectively). In patients with non-biopsy procedures (n = 79), participant satisfaction was significantly higher in the remimazolam group than in the midazolam group (median rated scale, 10 vs. 7, P = 0.042). Physician satisfaction and willingness to repeat the procedure were similar between groups. Although the incidence of adverse effects was similar between the groups and there was no significant difference, the midazolam group had a higher antidote administration rate than the remimazolam group (15.7% vs. 4.1%, P = 0.092). Remimazolam is effective and safe for achieving adequate sedation, with a shorter onset time and faster neuropsychiatric recovery than midazolam. It may be a new option for sedation during bronchoscopy.Trial registration: The trial registration number is NCT05994547, and the date of first registration is 16/08/2023.
Topics: Humans; Midazolam; Hypnotics and Sedatives; Bronchoscopy; Prospective Studies; Double-Blind Method; Benzodiazepines; Drug-Related Side Effects and Adverse Reactions
PubMed: 37993525
DOI: 10.1038/s41598-023-47271-w -
Cureus Dec 2023Premedication in anesthesia has long been used to reduce patient anxiety, increase patient compliance, and supplement the overall anesthetic. In pediatric populations,... (Review)
Review
Premedication in anesthesia has long been used to reduce patient anxiety, increase patient compliance, and supplement the overall anesthetic. In pediatric populations, premedication also has the indirect benefits of reducing parental anxiety as well as both the incidence and severity of emergence delirium. Oral midazolam, selected for its ease of administration, short duration of action, and reliable anxiolytic and amnestic effects, has been a favorite choice in this role for decades. The side effect profile of midazolam is also relatively benign, heavily dose-dependent, and easily managed in the perioperative setting. While midazolam appears to be an ideal adjunct in the anesthetic care of pediatric patients, there is a growing body of evidence suggesting prolonged benzodiazepine exposure causes neurodevelopmental changes in infants. This evidence, along with the 2017 Food and Drug Administration (FDA) warning labels for the use of select anesthetic medications, including midazolam in children under the age of three, has led to some debate in the anesthetic community over the continued use of this anesthetic for premedication in pediatric populations. This article aims to educate the reader on the history of midazolam as a premedication agent in pediatric populations and examine the evidence supporting and against its continued use in this role.
PubMed: 38089942
DOI: 10.7759/cureus.50309 -
Journal of Neurosurgery. Case Lessons Jul 2023Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to...
BACKGROUND
Tuberculosis is an airborne disease caused by Mycobacterium tuberculosis. Intracranial tuberculoma is a rare complication of extrapulmonary tuberculosis due to hematogenous spread to subpial and subependymal regions. Intracranial tuberculoma can occur with or without meningitis.
OBSERVATIONS
A 3-year-old male who had recently emigrated from Sudan presented to the emergency department with right-sided seizures lasting 30 minutes, which were aborted with levetiracetam and midazolam. Head computed tomography revealed a multilobulated left supratentorial mass with solid and cystic components and measuring 8.0 × 4.8 × 6.5 cm. The patient had successful resection of the mass, which was positive for M. tuberculosis. He was started on rifampin, isoniazid, pyrazinamide, ethambutol, and fluoroquinolone and was discharged home in stable condition.
LESSONS
A literature review on pediatric intracranial tuberculoma was performed, which included 48 studies (n = 49). The mean age was 8.8 ± 5.4 years with a slight female predilection (59%). Predominant solitary tuberculomas (63%) were preferentially managed with both resection and antituberculosis therapy (ATT), whereas multifocal tuberculomas were preferentially managed with ATT. Intracranial tuberculoma is a rare but treatable cause of space-occupying lesions in children. Clinicians should maintain a high level of suspicion in patients from endemic regions and involve the infectious disease service early.
PubMed: 37539871
DOI: 10.3171/CASE23236 -
Journal of Pain Research 2023Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to...
BACKGROUND
Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to discuss the developmental trends and evaluate the research hotspots using bibliometric methods for GI endoscopy anesthesia/sedation in the past two decades.
METHODS
The original and review articles published from 2001 to December 2022 related to GI endoscopy anesthesia/sedation were extracted from the Web of Science database. Four different softwares (CiteSpace, VOSviewer, and Bibliometrix, Online Analysis Platform of Literature Metrology (Bibliometric)) were used for this comprehensive analysis.
RESULTS
According to our retrieval strategy, we found a total of 3154 related literatures. Original research articles were 2855, and reviews were 299. There has been a substantial increase in the research on GI endoscopy anesthesia/sedation in recent 22 years. These publications have been cited 66,418 times, with a mean of 21.04 citations per publication. The US maintained a leading position in global research, with the largest number of publications (29.94%), and China ranked second (19.92%). Keyword burst and concurrence showed that conscious sedation, colonoscopy and midazolam were the most frequently occurring keywords.
CONCLUSION
Our research found that GI endoscopy anesthesia/sedation was in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that had significantly contributed to the field of GI endoscopy anesthesia/sedation. The US dominates this field, and the selection and dosage of sedative regimens have always been the foci of disease research to improve comfort and safety, while adverse events and risks arouse attention gradually. In the past 20 years, hotspots mainly focus on upper gastrointestinal endoscopy, gastroscopy, and esophagogastroduodenoscopy. These data would provide future directions for clinicians and researchers regarding GI endoscopy anesthesia/sedation.
PubMed: 37483407
DOI: 10.2147/JPR.S408811