RESUMO
BACKGROUND: Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24 hours) in the pediatric intensive care unit (PICU). OBJECTIVE: We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24 hours in mechanically ventilated children. METHODS: We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. RESULTS: A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4 mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p = 0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n = 4), hypersecretion (n = 14), tachycardia (n = 6), and nystagmus (n = 2). There were no significant changes in hemodynamic variables 24 h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24 hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p < 0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. CONCLUSION: The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.
Assuntos
Estado Terminal , Unidades de Terapia Intensiva Pediátrica , Ketamina , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Humanos , Estudos Prospectivos , Masculino , Feminino , Infusões Intravenosas , Pré-Escolar , Criança , Lactente , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Delírio , Respiração Artificial , Estudos de CoortesRESUMO
INTRODUCTION: Procedural sedation is crucial in gastrointestinal endoscopy, where propofol is commonly used but may lead to cardiovascular and respiratory side effects. Remimazolam, a new drug, offers advantages such as rapid onset and recovery. The sedation protocols for this population vary, requiring tailored titration of sedatives. The comparative safety of these drugs in elderly patients undergoing procedural sedation remains unclear, as previous studies primarily focus on the general population. We aimed to compare the safety profiles of remimazolam and propofol in this context. in elderly patients undergoing procedural sedation for gastrointestinal endoscopy. EVIDENCE ACQUISITION: We searched MEDLINE, EMBASE and Cochrane Library for randomized controlled trials (RCTs) comparing propofol with remimazolam in elderly patients undergoing procedural sedation. Our outcomes were the incidence of adverse effects. A trial sequential analysis (TSA) was conducted on all outcomes to assess the adequacy of the sample size in supporting our findings. EVIDENCE SYNTHESIS: We selected seven RCTs including 1499 patients, of whom 764 (50.96%) were randomized to receive remimazolam. Remimazolam exhibited a significantly lower risk of adverse events, including hypoxemia, respiratory depression, hypotension, bradycardia, and injection pain, compared to propofol. Incidences of PONV, dizziness and headache, did not significantly differ between the groups. The findings of the TSA indicated that our sample size was sufficiently large to render further studies inconsequential for most outcomes. CONCLUSIONS: Our findings suggest that in elderly patients having gastrointestinal endoscopy, remimazolam could be safer than propofol. This population may benefit from remimazolam's lower risk of adverse events, notably hypoxemia and respiratory depression.
Assuntos
Benzodiazepinas , Endoscopia Gastrointestinal , Hipnóticos e Sedativos , Propofol , Humanos , Propofol/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Idoso , Endoscopia Gastrointestinal/métodos , Benzodiazepinas/efeitos adversos , Benzodiazepinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sedação Consciente/métodos , Sedação Consciente/efeitos adversosRESUMO
OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.
Assuntos
Analgesia , Síndrome de Abstinência a Substâncias , Criança , Humanos , Adulto , Analgésicos Opioides/efeitos adversos , Estado Terminal/terapia , Desmame , Unidades de Terapia Intensiva Pediátrica , Hipnóticos e Sedativos/efeitos adversos , Síndrome de Abstinência a Substâncias/epidemiologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Doença Iatrogênica/epidemiologia , Doença Iatrogênica/prevenção & controleRESUMO
PURPOSE: The involvement of the orexin system in the physiopathology of insomnia has been rapidly increasing in understanding. In this sense, daridorexant was the third orexin receptor antagonist approved by the FDA in January 2022. This review aims to summarize the chemistry, pharmacodynamics, pharmacokinetics, efficacy, safety, and tolerability profile of daridorexant for the treatment of insomnia disorder. METHODS: We performed a review of daridorexant for the treatment of insomnia disorder. The search was carried out in Medline via PubMed, Embase, and clinical trials, up to March 2022. RESULTS: Daridorexant 25 and 50 mg had more significant improvement for the wake after sleep onset (WASO), latency to persistent sleep (LPS), and subjective total sleep time (sTST) than placebo. In addition, daridorexant 50 mg was better for Insomnia Daytime Symptoms and Impacts Questionnaire (IDSIQ) than placebo. The most common adverse events were nasopharyngitis and headache. CONCLUSION: Daridorexant was efficacious and safe. Studies that evaluate the long-term safety and compare daridorexant with benzodiazepines, benzodiazepine receptor agonists, sedative antidepressants, and other orexin receptor antagonists are required.
Assuntos
Distúrbios do Início e da Manutenção do Sono , Antidepressivos/uso terapêutico , Benzodiazepinas , Método Duplo-Cego , Humanos , Hipnóticos e Sedativos/efeitos adversos , Imidazóis , Lipopolissacarídeos , Antagonistas dos Receptores de Orexina/efeitos adversos , Orexinas , Pirrolidinas , Receptores de GABA-A , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológicoRESUMO
Abstract Objectives: Dexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery. Sources: Databases such as PubMed, Cochrane, Web of Science, WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb. 2021. Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation (SMD), odds ratio (OR) and 95% confidence interval (CI). Summary of the findings: Fifteen articles were included for this meta-analysis, and 9 articles for qualitative analysis. The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and reducing heart rate (HR) (SBP: SMD = -0.35,95% CI: -0.72, 0.01; MAP: SMD = -0.83, 95% CI: -1.87,0.21; DBP: SMD = -0.79,95% CI: -1.66,0.08; HR: SMD = -1.71,95% CI: -2.29, -1.13). In addition, the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group. Conclusions: The application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability, and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences.
Assuntos
Humanos , Criança , Dexmedetomidina/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Pressão Sanguínea , Hemodinâmica , Hipnóticos e Sedativos/efeitos adversosRESUMO
No prior studies have evaluated the efficacy and safety of zolpidem and zopiclone to treat insomnia of demented patients. This randomized, triple-blind, placebo-controlled clinical trial used these drugs to treat patients with probable, late onset Alzheimer's dementia (AD) (DSM V and NINCDS-ADRDA criteria) exhibiting insomnia (DSM V criteria and nocturnal NPI scores ≥ 2). Actigraphic records were performed for 7 days at baseline and for 14 days during the treatment period in 62 patients aged 80.5 years in average and randomized at a 1:1:1 ratio for administration of zolpidem 10 mg/day, zopiclone 7.5 mg/day or placebo. Primary endpoint was the main nocturnal sleep duration (MNSD), whereas secondary outcomes were the proportion of the night time slept, awake time after sleep onset (WASO), nocturnal awakenings, total daytime sleep time and daytime naps. Cognitive and functional domains were tested before and after drug/placebo use. Three participants under zopiclone use had intervention interrupted due to intense daytime sedation and worsened agitation with wandering. Zopiclone produced an 81 min increase in MNSD (95% confidence interval (CI): -0.8, 163.2), a 26 min reduction in WASO (95% CI: -56.2, 4.8) and a 2-episode decrease in awakening per night (95% CI: -4.0, 0.4) in average compared to placebo. Zolpidem yielded no significant difference in MNSD despite a significant 22 min reduction in WASO (95% CI: -52.5, 8.3) and a reduction of 1 awakening each night (95% CI: -3.4, 1.2) in relation to placebo. There was a 1-point reduction in mean performance in the symbols search test among zolpidem users (95% CI: -4.1, 1.5) and an almost eight-point reduction in average scores in the digit-symbol coding test among zopiclone users (95% CI: -21.7, 6.2). In summary, short-term use of zolpidem or zopiclone by older insomniacs with AD appears to be clinically helpful, even though safety and tolerance remain issues to be personalized in healthcare settings and further investigated in subsequent trials. This trial was registered in ClinicalTrials.gov Identifier: NCT03075241.
Assuntos
Doença de Alzheimer , Distúrbios do Início e da Manutenção do Sono , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/tratamento farmacológico , Compostos Azabicíclicos , Método Duplo-Cego , Humanos , Hipnóticos e Sedativos/efeitos adversos , Piperazinas , Distúrbios do Início e da Manutenção do Sono/complicações , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Zolpidem/efeitos adversosRESUMO
OBJECTIVE: To evaluate dependence among chronic benzodiazepine and Z-drug users in Brazil. METHODS: Chronic users of benzodiazepines (n=94), Z-drugs (n=74), or both (n=11) were recruited from the community, underwent a psychiatric evaluation and completed self-report instruments on hypnotic dependence, insomnia, anxiety, and depression. Users of benzodiazepines and Z-drugs were compared using t-tests, and logistic regression models were employed to explore significant predictors of a dependence diagnosis. RESULTS: There was no difference in the prevalence of dependence among benzodiazepine (77.2%) and Z-drug (69.4%) users. Benzodiazepine users reported increased psychosocial aspects of dependence, anxiety, and depression. Preoccupation with the availability of medication (prevalence ratio [PR] = 2.39 [1.15-5.20]) and insomnia (PR = 1.10 [1.02-1.19]) were associated with a diagnosis of dependence (n=175). CONCLUSION: The prevalence of dependence was similar among both drug classes. The increased self-reported dependence, anxiety, and depression among benzodiazepine users may be due to behavioral rather than pharmacological aspects of medication use. Behaviors related to hypnotic use were important predictors of dependence.
Assuntos
Distúrbios do Início e da Manutenção do Sono , Transtornos Relacionados ao Uso de Substâncias , Ansiedade/epidemiologia , Benzodiazepinas/efeitos adversos , Humanos , Hipnóticos e Sedativos/efeitos adversos , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Distúrbios do Início e da Manutenção do Sono/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
OBJECTIVES: Dexmedetomidine (DEX) is a highly selective alpha-2 adrenergic receptor agonist, which is the main sedative in the intensive care unit. This study aims to investigate the effectiveness and adverse events of DEX in maintaining hemodynamic stability in pediatric cardiac surgery. SOURCES: Databases such as PubMed, Cochrane, Web of Science, WANFANG STATA and China National Knowledge Infrastructure were searched for articles about the application of DEX in maintaining hemodynamic stability during and after pediatric cardiac surgery up to 18th Feb. 2021. Only randomized controlled trials were included and random-effects model meta-analysis was applied to calculate the standardized mean deviation (SMD), odds ratio (OR) and 95% confidence interval (CI). SUMMARY OF THE FINDINGS: Fifteen articles were included for this meta-analysis, and 9 articles for qualitative analysis. The results showed that preoperative prophylaxis and postoperative recovery of DEX in pediatric patients undergoing cardiac surgery were effective in maintaining systolic blood pressure (SBP), mean arterial pressure (MAP), diastolic blood pressure (DBP) and reducing heart rate (HR) (SBP: SMD = -0.35,95% CI: -0.72, 0.01; MAP: SMD = -0.83, 95% CI: -1.87,0.21; DBP: SMD = -0.79,95% CI: -1.66,0.08; HR: SMD = -1.71,95% CI: -2.29, -1.13). In addition, the frequency of Junctional Ectopic Tachycardia in the DEX treatment group was lower than that in the placebo group. CONCLUSIONS: The application of DEX for preoperative prophylaxis and postoperative recovery in pediatric cardiac surgery patients are effective in maintaining hemodynamic stability, and the clinical dose of DEX is not significantly related to the occurrence of pediatric adverse events which may be related to individual differences.
Assuntos
Procedimentos Cirúrgicos Cardíacos , Dexmedetomidina , Pressão Sanguínea , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Criança , Dexmedetomidina/efeitos adversos , Hemodinâmica , Humanos , Hipnóticos e Sedativos/efeitos adversosRESUMO
Acute ischemic stroke is associated with pulmonary complications, and often dexmedetomidine and propofol are used to decrease cerebral metabolic rate. However, it is unknown the immunomodulatory actions of dexmedetomidine and propofol on brain and lungs during acute ischemic stroke. The effects of dexmedetomidine and propofol were compared on perilesional brain tissue and lung damage after acute ischemic stroke in rats. Further, the mean amount of both sedatives was directly evaluated on alveolar macrophages and lung endothelial cells primarily extracted 24-h after acute ischemic stroke. In twenty-five Wistar rats, ischemic stroke was induced and after 24-h treated with sodium thiopental (STROKE), dexmedetomidine and propofol. Dexmedetomidine, compared to STROKE, reduced diffuse alveolar damage score [median(interquartile range); 12(7.8-15.3) vs. 19.5(18-24), p = 0.007)], bronchoconstriction index [2.28(2.08-2.36) vs. 2.64(2.53-2.77), p = 0.006], and TNF-α expression (p = 0.0003), while propofol increased VCAM-1 expression compared to STROKE (p = 0.0004). In perilesional brain tissue, dexmedetomidine, compared to STROKE, decreased TNF-α (p = 0.010), while propofol increased VCAM-1 compared to STROKE (p = 0.024). In alveolar macrophages and endothelial cells, dexmedetomidine decreased IL-6 and IL-1ß compared to STROKE (p = 0.002, and p = 0.040, respectively), and reduced IL-1ß compared to propofol (p = 0.014). Dexmedetomidine, but not propofol, induced brain and lung protection in experimental acute ischemic stroke.
Assuntos
Encéfalo/efeitos dos fármacos , Dexmedetomidina/administração & dosagem , Hipnóticos e Sedativos/administração & dosagem , AVC Isquêmico/tratamento farmacológico , Pulmão/efeitos dos fármacos , Propofol/administração & dosagem , Animais , Isquemia Encefálica/prevenção & controle , Dexmedetomidina/efeitos adversos , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Hipnóticos e Sedativos/efeitos adversos , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Macrófagos Alveolares/efeitos dos fármacos , Masculino , Propofol/efeitos adversos , Ratos , Ratos Wistar , Tiopental , Fator de Necrose Tumoral alfa/biossíntese , Molécula 1 de Adesão de Célula Vascular/biossínteseRESUMO
BACKGROUND: Benzodiazepines are used for perioperative conscious sedation. However, its use may be associated with paradoxical reactions. The known risk factors for these reactions are age, alcohol and drug abuse and psychiatric disorders. AIM: To assess the incidence and impact of risk factors of paradoxical reactions to midazolam. MATERIAL AND METHODS: Cross sectional study of 218 patients aged 50 ± 16 years (51% women) scheduled for elective surgical procedures under regional anesthesia and midazolam sedation. The paradoxical reactions were classified according to their severity in three categories. RESULTS: The incidence of paradoxical reactions to midazolam was 8.3% (95% confidence interval (CI) 5.0-12.7). All were mild and only 28% of the affected patients required pharmacological treatment, none of them flumazenil. A multivariable logistic regression model showed that the variables independently associated with a paradoxical reaction to midazolam were the use of psychoactive medications (Odds Ratio (OR) = 3.4 [1.1-11], p = 0.04, and the dose of midazolam (OR 1.35 [1.03-1.78], p = 0.03. CONCLUSIONS: The incidence of paradoxical reactions to midazolam was 8,3% and all were mild. Their risk factors are the use of psychoactive medications and the use of higher doses of midazolam.