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Cureus Jul 2023Background Preoperative anxiety is common in children undergoing surgery. When anxiety is identified or suspected, there are several strategies typically used to manage...
Background Preoperative anxiety is common in children undergoing surgery. When anxiety is identified or suspected, there are several strategies typically used to manage it. Perhaps the most common is anxiolytic premedication or parental presence at induction. Medications such as midazolam have been associated with adverse effects, such as a slower wakeup, and require timing of administration, while parental presence can be disturbing to the parent and divert the attention of the operating room team. A more recent option is distraction via electronic tablets. The purpose of this study was to retrospectively investigate and quantify any change in the use of midazolam, the most common anxiolytic approach at our institution, and any change in the length of time in the post-anesthesia care unit (PACU) following the introduction of tablet computers to a pediatric ambulatory surgical center. Methods We conducted an IRB-approved retrospective chart review of 13,790 pediatric patients ages one to 18 undergoing outpatient elective surgeries at the University of Florida (UF) Children's Surgical Center over a five-year period. A univariate analysis was conducted using the Fisher's Exact test and interrupted time series analysis to determine differences between midazolam administration and PACU times, with interruption occurring at tablet implementation. A multivariable analysis and sensitivity analyses were performed to confirm the findings of the univariate analysis. Results On univariate analysis, tablet availability was associated with both a decreased preoperative oral midazolam administration (odds ratio (OR) 0.158, 95% confidence interval (CI): 0.140 to 0.179, P-value <0.001) and a decreased PACU length of stay (-17.4 min, 95% CI: -19.6 to -15.3 min, P-value <0.001). The association with decreased preoperative midazolam administration held after multivariable analysis (adjusted OR 0.207, 95% CI: 0.154 to 0.278, P-value <0.001), but PACU length of stay was not statistically significant (-9.1 min, 95% CI: -20.6 to 2.4, P-value = 0.12). These results were confirmed on sensitivity analysis, with tablet availability continuing to be associated with decreased preoperative oral midazolam administration but not with reduced PACU length of stay. Conclusion Our results demonstrate that computer tablets were associated with a significant decrease in the frequency of midazolam administration and consequently may reduce preoperative pediatric anxiety. We did not find an associated change in PACU length of stay following the introduction of tablets. Tablets present a unique distraction alternative to chemical anxiolysis for institutions seeking to reduce medication use in pediatric patients.
PubMed: 37637603
DOI: 10.7759/cureus.42553 -
Acta Medica Philippina 2024Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy...
Lung cancer is the leading cause of cancer death worldwide. It may present as airway obstruction in a patient with endobronchial masses. Endobronchial brachytherapy (EBBT) has been shown to provide palliative therapy. It is the insertion of a radioactive material near the mass to reduce tumor size, thereby improving airway obstruction. This is the first case of EBBT done in our institution during the COVID-19 pandemic. A 53-year-old male, 60 kg, ASA Physical Status 2 for hypertension, smoker, malignancy, and previous pulmonary tuberculosis patient, presented with a cough and dyspnea. An endobronchial mass almost obstructing the right mainstem bronchus was seen on a computed tomography (CT) scan. He was diagnosed with squamous cell carcinoma of the lung and underwent radiotherapy and erlotinib chemotherapy. On repeat CT scan, there was no noted decrease in the size of the mass. EBBT was suggested, and a multi-disciplinary team was formed for the planned procedure. Pulmonology, radiation oncology, and anesthesiology teams were identified, and thorough planning was done prior to the actual procedure. Three fractions of EBBT were done under sedation using midazolam, fentanyl, and dexmedetomidine infusion. Lidocaine spray and transtracheal block were also performed as adjuncts prior to sedation. The procedure went as planned, and points for improvement were discussed for subsequent fractions. Due to persistent cough and discomfort from the catheter, additional ipratropium nebulization for minimization of secretions, and oral dextromethorphan for cough suppression were incorporated. After each fraction, the patient was monitored post-procedure for any side effects both from the radiotherapy and anesthetic technique. Qualitative reduction in mass size was noted in subsequent fractions. The patient was able to complete 3 fractions and was advised to follow-up after a month. EBBT is an emerging palliative and treatment modality for lung cancer, especially for intraluminal masses. Anesthetic considerations will depend on each case's characteristics such as airway anatomy, patient comfort and capacity, and procedural requirements. Conscious sedation with topical anesthesia is an adequate and appropriate anesthetic option, especially in cases where severe airway obstruction may compromise ventilation if airway reflexes are blunted. A multidisciplinary approach with different services and stakeholders is important for the proper planning, execution, and management of such patients.
PubMed: 38836083
DOI: 10.47895/amp.v58i9.8839 -
Heliyon Feb 2024Bibliometric analysis methods were used to evaluate pediatric dental sedation research and to identify topical hotspots using quantitative and qualitative methodologies. (Review)
Review
STATEMENT OF PROBLEM
Bibliometric analysis methods were used to evaluate pediatric dental sedation research and to identify topical hotspots using quantitative and qualitative methodologies.
PURPOSE
To conduct bibliometric analysis on the retrieved data and to foresee the development of trends and hotspots in this research area.
MATERIAL AND METHODS
We retrieved appropriate research articles from the Web of Science Core Collection on January 1, 2023. VOSviewer, Citespace and the Bibliometrics website were used to conduct bibliometric analysis on the retrieved data. GraphPad Prism 10.0 (GraphPad, San Diego, CA, USA) was used to conduct the statistical analysis.
RESULTS
A total of 396 publications on pediatric sedation in dentistry, published between 1993 and 2022, were retrieved from online databases. The USA published most papers. Furthermore, the most frequent countries who cooperated were the USA and Canada. Six of the top ten publishing establishments were USA based. Papers on the research have appeared primarily in the journals of Dentistry and Anesthesiology. Keyword co-occurrence and co-citation cluster analysis revealed that the most common topics mainly were: dental anxiety; conscious sedation; dental caries; midazolam; propofol; hypoxemia.
CONCLUSIONS
During the three decades, the focus of pediatric sedation research has been on drugs, dental anxiety and procedural sedation. Keyword burst detection indicated that procedural sedation; adverse event; respiratory depression is an emerging research hotspot.
PubMed: 38333804
DOI: 10.1016/j.heliyon.2024.e25527 -
Heart & Lung : the Journal of Critical... 2023Post intensive care syndrome is defined as the presence of any impairment affecting the physical, psychiatric, or cognitive domains as a result of critical illnesses.
BACKGROUND
Post intensive care syndrome is defined as the presence of any impairment affecting the physical, psychiatric, or cognitive domains as a result of critical illnesses.
OBJECTIVES
To explore functional, cognitive and psychological outcomes at 30 days post hospital discharge among survivors of COVID-19-associated acute respiratory distress syndrome, who required mechanical ventilation.
METHODS
Prospective cohort study. We included adult patients with COVID-19-associated acute respiratory distress syndrome, invasively ventilated in two ICUs in Buenos Aires. We measured functional, cognitive and psychological impairments with Barthel index, Montreal Cognitive Assessment test, Patient Health Questionnaire-9 and General Anxiety Disorder-7. Primary outcome was post-intensive care syndrome. Secondary outcome was mortality at 60 days.
RESULTS
We admitted 40 patients, median age was 69 (60-75) and mostly male (75%). Mortality at 60 days was 37%. Cox regression analysis identified diabetes and Apache II as independent predictors of mortality. Out of 22 patients studied, 14 (64%) developed PICS after discharge. With a physical, cognitive and psychological impairment in 64%, 41% and 32% of patients, respectively. Obesity, days of mechanical ventilation, Apache II, vasopressors use, delirium duration and cumulative midazolam dose were associated with functional dependence.
CONCLUSIONS
We identified a high prevalence of functional, cognitive and mental impairment at 30 days after hospital discharge in COVID-19-associated acute respiratory distress syndrome survivors, invasively ventilated. The physical domain was the most frequently affected. These findings suggest the need for long-term follow-up of this population.
Topics: Adult; Humans; Male; Aged; Female; Prospective Studies; COVID-19; Critical Illness; Respiration, Artificial; Pandemics; Intensive Care Units; Critical Care; Survivors; Respiratory Distress Syndrome
PubMed: 37348211
DOI: 10.1016/j.hrtlng.2023.06.021 -
Neonatology 2024There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate...
INTRODUCTION
There is no consensus regarding the efficacy of add-on therapy with levetiracetam (LEV) in the treatment of seizures in neonates. The aim of this study was to evaluate the efficacy of add-on therapy with LEV for achieving >80% seizure reduction after phenobarbital (PB) treatment.
METHODS
Retrospective cohort study of near term neonates admitted to the neonatal intensive care unit with EEG-confirmed seizures despite treatment with PB as first-line therapy and using LEV as 2nd-, 3rd- or 4th-line treatment. Antiseizure medication was administered according to national guidelines. All neonates were monitored with 2-channel amplitude-integrated electroencephalography. The total seizure burden in minutes, 2 h before and 4 h after administration of LEV, was calculated using raw EEG. Primary outcome was the efficacy of LEV in achieving >80% seizure reduction. The efficacy of additional midazolam (MDZ) and lidocaine (LDC) was also calculated.
RESULTS
A total of 47 full-term neonates were included. The mean total loading dose of LEV was 40 mg/kg (36-44 mg/kg). Seizure etiology consisted of hypoxic-ischemic encephalopathy (n = 11), hemorrhagic or ischemic stroke (n = 16), central nervous system infection (n = 8), genetic (n = 8), metabolic disorders (n = 3), and unknown (n = 1). Following LEV administration, >80% seizure reduction was observed in 17% (8/47) of neonates, whereas it was 23% (6/26) after MDZ and 92% (23/25) after LDC administration.
DISCUSSION
Although the cumulative loading dose of LEV was low and the group of infants studied was heterogeneous, the efficacy of LEV as add-on therapy for the treatment of seizures in neonates was limited. The highest seizure reduction rate was seen after LDC administration.
Topics: Infant, Newborn; Humans; Levetiracetam; Anticonvulsants; Retrospective Studies; Seizures; Electroencephalography; Midazolam
PubMed: 38113859
DOI: 10.1159/000535499 -
The Journal of Pharmacology and... Jan 2024This article describes recent advances in the use of neurosteroids as novel anticonvulsants for refractory status epilepticus (RSE) and as medical countermeasures (MCs)... (Review)
Review
Neurosteroids as Novel Anticonvulsants for Refractory Status Epilepticus and Medical Countermeasures for Nerve Agents: A 15-Year Journey to Bring Ganaxolone from Bench to Clinic.
This article describes recent advances in the use of neurosteroids as novel anticonvulsants for refractory status epilepticus (RSE) and as medical countermeasures (MCs) for organophosphates and chemical nerve agents (OPNAs). We highlight a comprehensive 15-year journey to bring the synthetic neurosteroid ganaxolone (GX) from bench to clinic. RSE, including when caused by nerve agents, is associated with devastating morbidity and permanent long-term neurologic dysfunction. Although recent approval of benzodiazepines such as intranasal midazolam and intranasal midazolam offers improved control of acute seizures, novel anticonvulsants are needed to suppress RSE and improve neurologic function outcomes. Currently, few anticonvulsant MCs exist for victims of OPNA exposure and RSE. Standard-of-care MCs for postexposure treatment include benzodiazepines, which do not effectively prevent or mitigate seizures resulting from nerve agent intoxication, leaving an urgent unmet medical need for new anticonvulsants for RSE. Recently, we pioneered neurosteroids as next-generation anticonvulsants that are superior to benzodiazepines for treatment of OPNA intoxication and RSE. Because GX and related neurosteroids that activate extrasynaptic GABA-A receptors rapidly control seizures and offer robust neuroprotection by reducing neuronal damage and neuroinflammation, they effectively improve neurologic outcomes after acute OPNA exposure and RSE. GX has been selected for advanced, Biomedical Advanced Research and Development Authority-supported phase 3 trials of RSE and nerve agent seizures. In addition, in mechanistic studies of neurosteroids at extrasynaptic receptors, we identified novel synthetic analogs with features that are superior to GX for current medical needs. Development of new MCs for RSE is complex, tedious, and uncertain due to scientific and regulatory challenges. Thus, further research will be critical to fill key gaps in evaluating RSE and anticonvulsants in vulnerable (pediatric and geriatric) populations and military persons. SIGNIFICANCE STATEMENT: Following organophosphate and nerve agent intoxication, refractory status epilepticus (RSE) occurs despite benzodiazepine treatment. RSE occurs in 40% of status epilepticus patients, with a 35% mortality rate and significant neurological morbidity in survivors. To treat RSE, neurosteroids are better anticonvulsants than benzodiazepines. Our pioneering use of neurosteroids for RSE and nerve agents led us to develop ganaxolone as a novel anticonvulsant and neuroprotectant with significantly improved neurological outcomes. This article describes the bench-to-bedside journey of bringing neurosteroid therapy to patients, with ganaxolone leading the way.
Topics: Humans; Child; Aged; Anticonvulsants; Nerve Agents; Neurosteroids; Midazolam; Medical Countermeasures; Status Epilepticus; Seizures; Benzodiazepines; Organophosphates; Pregnanolone
PubMed: 37977814
DOI: 10.1124/jpet.123.001816 -
Cureus Jul 2023Objective To describe the development process of a patient-centered initiative focused on improving primary care health outcomes of patients with intellectual and...
Objective To describe the development process of a patient-centered initiative focused on improving primary care health outcomes of patients with intellectual and developmental disabilities (IDD) and needle-related anxiety using evidence-based practices and novel approaches that can be implemented in outpatient settings. The overall outcome of the program is to increase vaccine uptake and accessibility in the IDD population as well as improve needle-related procedures in primary care settings to be more humane and effective. Methods The development process occurred in the context of a large healthcare system serving a diverse patient population in the U.S. and was led by an expert committee made of an multidisciplinary team of physicians, psychologists, ambulatory and clinic nurses, pharmacists, and anesthesiologists committed to promoting quality healthcare for the IDD population. Committee members were recruited within the healthcare system based on their relevant expertise. The methodology included an iterative and collaborative process that took place over three development phases: ideation and design, literature review and synthesis, and expert engagement. The ideation and design phase included a series of planning meetings among the expert committee, in which committee members identified preliminary concerns based on their expertise in the field and background knowledge on the current procedures related to improving routine care for individuals with IDD and/or needle-related anxiety. The literature review and synthesis phase led to the development of an annotated bibliography of research and clinical guidelines that synthesized findings on needle anxiety in clinical care. The expert engagement phase included all Committee members meeting for a final discussion to establish a tiered approach to utilizing evidence-based strategies that could be implemented across clinics within the healthcare system. Results The multidisciplinary team of experts developed a three-tier system, deployed sequentially as needed. The first tier focuses on training nurses in evidence-based behavioral modification strategies to implement as standard of care. The second tier uses the addition of a distraction device and topical analgesic to reduce anxiety in patients with slightly elevated procedural anxiety. The third tier involves a novel minimal sedation protocol using intranasal midazolam for patients with needle phobia that can be administered in an outpatient setting. Conclusion The Needle Anxiety Program eases the administration of needle-related medical procedures in the primary care setting for patients with IDD and needle-related anxiety. The use of evidence-based practices and a novel minimal sedation protocol for individuals with needle phobia assists in the completion of routine healthcare procedures, such as vaccinations and phlebotomy, in a patient-preferred setting. The purpose of delineating needle-related processes and procedures through the Needle Anxiety Program is to reduce health disparities for patients with IDD and promote uptake of the Needle Anxiety Program in similar healthcare settings.
PubMed: 37605699
DOI: 10.7759/cureus.42253 -
Journal of Affective Disorders May 2024Due to its rapid antidepressant effect, ketamine has recently been clinically translated for people with treatment-resistant depression. However, its cognitive profile... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Due to its rapid antidepressant effect, ketamine has recently been clinically translated for people with treatment-resistant depression. However, its cognitive profile remains unclear, particularly with repeated and higher doses. In the present study, we report the cognitive results from a recent large multicentre randomised controlled trial, the Ketamine for Adult Depression Study (KADS).
METHODS
In this randomised, double-blind, active-controlled, parallel group, multicentre phase 3 trial study we investigated potential cognitive changes following repeated treatment of subcutaneous racemic ketamine compared to an active comparator, midazolam, over 4 weeks, which involved two cohorts; Cohort 1 involved a fixed dose treatment protocol (0.5 mg/kg ketamine), Cohort 2 involved a dose escalation protocol (0.5-0.9 mg/kg) based on mood outcomes. Participants with treatment-resistant Major Depressive Disorder (MDD) were recruited from 7 mood disorder centres and were randomly assigned to receive ketamine (Cohort 1 n = 33; Cohort 2 n = 53) or midazolam (Cohort 1 n = 35; Cohort 2 n = 53) in a 1:1 ratio. Cognitive measurements were assessed at baseline and at the end of randomised treatment.
RESULTS
Results showed that in Cohort 1, there were no differences between ketamine and midazolam in cognitive outcomes. For Cohort 2, there was similarly no difference between conditions for cognitive outcomes.
LIMITATIONS
The study included two Cohorts with different dosing regimes.
CONCLUSIONS
The findings support the cognitive safety of repeated fixed and escalating doses at least in the short-term in people with treatment resistant MDD.
Topics: Adult; Humans; Ketamine; Midazolam; Depression; Depressive Disorder, Major; Double-Blind Method; Depressive Disorder, Treatment-Resistant; Cognition; Treatment Outcome
PubMed: 38378088
DOI: 10.1016/j.jad.2024.02.052 -
Clinical and Translational Science Nov 2023Ziritaxestat, an autotaxin inhibitor, was under development for the treatment of idiopathic pulmonary fibrosis. It is a substrate of cytochrome P450 3A4 (CYP3A4) and...
Ziritaxestat, an autotaxin inhibitor, was under development for the treatment of idiopathic pulmonary fibrosis. It is a substrate of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein and a weak inhibitor of the CYP3A4 and OATP1B1 pathways. We developed a physiologically based pharmacokinetic (PBPK) network interaction model for ziritaxestat that incorporated its metabolic and transporter pathways, enabling prediction of its potential as a victim or perpetrator of drug-drug interactions (DDIs). Concurrently, we evaluated CYP3A4 autoinhibition, including time-dependent inhibition. In vitro information and clinical data from healthy volunteer studies were used for model building and validation. DDIs with rifampin, itraconazole, voriconazole, pravastatin, and rosuvastatin were predicted, followed by validation against a test dataset. DDIs of ziritaxestat as a victim or perpetrator were simulated using the final model. Predicted-to-observed DDI ratios for the maximum plasma concentration (C ) and the area under the plasma concentration-time curve (AUC) were within a two-fold ratio for both the metabolic and transporter-mediated simulated DDIs. The predicted impact of autoinhibition/autoinduction or time-dependent inhibition of CYP3A4 was a 12% decrease in exposure. Model-based predictions for ziritaxestat as a victim of DDIs with a moderate CYP3A4 inhibitor (fluconazole) suggested a 2.6-fold increase in the AUC of ziritaxestat, while multiple doses of a strong inhibitor (voriconazole) would increase the AUC by 15-fold. Efavirenz would yield a three-fold decrease in the AUC of ziritaxestat. As a perpetrator, ziritaxestat was predicted to increase the AUC of the CYP3A4 index substrate midazolam by 2.7-fold. An overarching PBPK model was developed that could predict DDI liability of ziritaxestat for both CYP3A4 and the transporter pathways.
Topics: Humans; Cytochrome P-450 CYP3A; Voriconazole; Models, Biological; Area Under Curve; Drug Interactions
PubMed: 37667518
DOI: 10.1111/cts.13622 -
Archives of Toxicology Apr 2024Recent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by...
Cardiovascular responses of adult male Sprague-Dawley rats following acute organophosphate intoxication and post-exposure treatment with midazolam with or without allopregnanolone.
Recent experimental evidence suggests combined treatment with midazolam and allopregnanolone is more effective than midazolam alone in terminating seizures triggered by acute organophosphate (OP) intoxication. However, there are concerns that combined midazolam and allopregnanolone increases risk of adverse cardiovascular events. To address this, we used telemetry devices to record cardiovascular responses in adult male Sprague-Dawley rats acutely intoxicated with diisopropylfluorophosphate (DFP). Animals were administered DFP (4 mg/kg, sc), followed immediately by atropine (2 mg/kg, i.m.) and 2-PAM (25 mg/kg, i.m.). At 40 min post-exposure, a subset of animals received midazolam (0.65 mg/kg, im); at 50 min, these rats received a second dose of midazolam or allopregnanolone (12 mg/kg, im). DFP significantly increased blood pressure by ~ 80 mmHg and pulse pressure by ~ 34 mmHg that peaked within 12 min. DFP also increased core temperature by ~ 3.5 °C and heart rate by ~ 250 bpm that peaked at ~ 2 h. Heart rate variability (HRV), an index of autonomic function, was reduced by ~ 80%. All acute (within 15 min of exposure) and two-thirds of delayed (hours after exposure) mortalities were associated with non-ventricular cardiac events within 10 min of cardiovascular collapse, suggesting that non-ventricular events should be closely monitored in OP-poisoned patients. Compared to rats that survived DFP intoxication without treatment, midazolam significantly improved recovery of cardiovascular parameters and HRV, an effect enhanced by allopregnanolone. These data demonstrate that midazolam improved recovery of cardiovascular and autonomic function and that the combination of midazolam and allopregnanolone may be a better therapeutic strategy than midazolam alone.
Topics: Humans; Rats; Male; Animals; Rats, Sprague-Dawley; Midazolam; Pregnanolone; Isoflurophate; Organophosphates; Brain; Organophosphate Poisoning
PubMed: 38305864
DOI: 10.1007/s00204-023-03679-x