RESUMEN
BACKGROUND: Sedation during flexible bronchoscopy (FB) should maintain an adequate respiratory drive, ensure maximum comfort for the patient, and warrant that the objectives of the procedure are achieved. Nevertheless, the optimal sedation method for FB has yet to be established. This study aimed to compare the standard recommended combination of midazolam-fentanyl (MF) with that of dexmedetomidine-ketamine (DK) for patient sedation during FB. METHODS: Patients subjected to FB were randomly assigned to a DK (n = 25) and an MF group (n = 25). The primary outcome was the rate of critical desaturation events (arterial oxygen saturation < 80% with nasal oxygen supply 2 L/min). Secondary outcomes included sedation depth, hemodynamic complications, adverse events, and patient and bronchoscopist satisfaction. RESULTS: The incidence rates of critical desaturation events were similar between the two groups (DK: 12% vs. MF: 28%, p = 0.289). DK achieved deeper maximum sedation levels (higher Ramsay - lower Riker scale; p < 0.001) and was associated with longer recovery times (p < 0.001). Both groups had comparable rates of hemodynamic and other complications. Patient satisfaction was similar between the two groups, but bronchoscopist satisfaction was higher with the DK combination (p = 0.033). CONCLUSION: DK demonstrated a good safety profile in patients subjected to FB and achieved more profound sedation and better bronchoscopist satisfaction than the standard MF combination without increasing the rate of adverse events.
Asunto(s)
Broncoscopía , Dexmedetomidina , Fentanilo , Hipnóticos y Sedantes , Ketamina , Midazolam , Satisfacción del Paciente , Humanos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/efectos adversos , Broncoscopía/métodos , Fentanilo/administración & dosificación , Masculino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Ketamina/administración & dosificación , Ketamina/efectos adversos , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Método Simple Ciego , Anciano , Adulto , Sedación Consciente/métodosRESUMEN
AIMS: We report on investigations exploring the P2X3-receptor antagonist filapixant's effect on taste perception and cough-reflex sensitivity and describe its pharmacokinetics, including its CYP3A4-interaction potential. METHODS: In a randomized, placebo-controlled, double-blind study, 3 × 12 healthy men (18-45 years) were assigned (3:1) to filapixant (20, 80 or 250 mg by mouth) or placebo twice daily over 2 weeks. A single dose of midazolam (1 mg), a CYP3A4 substrate, was administered with and without filapixant. Assessments included a taste-strips test, a taste questionnaire, cough challenge with adenosine triphosphate, adverse event reports and standard safety assessments. RESULTS: Taste disturbances were observed mainly in the 250-mg group: six of nine participants (67%) in this group reported hypo- or dysgeusia in the questionnaire; eight participants (89%) reported taste-related adverse events. Five participants (56%) had a decrease in overall taste-strips-test scores ≥2 points (point estimate -1.1 points, 90% confidence interval [-3.3; 1.1]). Cough counts increased with adenosine triphosphate concentration but without major differences between treatments. Filapixant exposure increased proportionally to dose. Co-administration of filapixant had no clinically relevant effect on midazolam pharmacokinetics. Area under the concentration-time curve ratios and 90% confidence intervals were within 80-125%. No serious or severe adverse events were reported. CONCLUSIONS: Overall, filapixant was safe and well tolerated, apart from mild, transient taste disturbances. Such disturbances occurred more frequently than expected based on (in vitro) receptor-selectivity data, suggesting that other factors than P2X3:P2X2/3 selectivity might also play an important role in this context. The cough-challenge test showed no clear treatment effect. Filapixant has no clinically relevant CYP3A4 interaction potential.
Asunto(s)
Citocromo P-450 CYP3A , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Midazolam , Antagonistas del Receptor Purinérgico P2X , Humanos , Masculino , Adulto , Citocromo P-450 CYP3A/metabolismo , Antagonistas del Receptor Purinérgico P2X/administración & dosificación , Antagonistas del Receptor Purinérgico P2X/farmacocinética , Antagonistas del Receptor Purinérgico P2X/efectos adversos , Antagonistas del Receptor Purinérgico P2X/farmacología , Método Doble Ciego , Adulto Joven , Midazolam/farmacocinética , Midazolam/administración & dosificación , Midazolam/efectos adversos , Adolescente , Voluntarios Sanos , Persona de Mediana Edad , Tos/inducido químicamente , Gusto/efectos de los fármacos , Receptores Purinérgicos P2X3/efectos de los fármacos , Receptores Purinérgicos P2X3/metabolismoRESUMEN
Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.
Asunto(s)
Antagonistas Adrenérgicos beta , Extinción Psicológica , Miedo , Memoria , Midazolam , Propranolol , Propranolol/farmacología , Propranolol/administración & dosificación , Animales , Miedo/efectos de los fármacos , Extinción Psicológica/efectos de los fármacos , Ratas , Humanos , Antagonistas Adrenérgicos beta/farmacología , Antagonistas Adrenérgicos beta/administración & dosificación , Masculino , Memoria/efectos de los fármacos , Midazolam/farmacología , Midazolam/administración & dosificación , Midazolam/efectos adversos , Adulto , Teorema de Bayes , Femenino , Condicionamiento Clásico/efectos de los fármacos , Adulto JovenRESUMEN
BACKGROUND: Proper sedation of patients, particularly elderly individuals, who are more susceptible to sedation-related complications, is of significant importance in endoscopic retrograde cholangiopancreatography (ERCP). This study aims to assess the safety and efficacy of a low-dose combination of midazolam, alfentanil, and propofol for deep sedation in elderly patients undergoing ERCP, compared to a group of middle-aged patients. METHODS: The medical records of 610 patients with common bile duct stones who underwent elective ERCP under deep sedation with a three-drug regimen, including midazolam, alfentanil, and propofol at Shandong Provincial Third Hospital from January 2023 to September 2023 were retrospectively reviewed in this study. Patients were categorized into three groups: middle-aged (50-64 years, n = 202), elderly (65-79 years, n = 216), and very elderly (≥ 80 years, n = 192). Intraoperative vital signs and complications were compared among these groups. RESULTS: The three groups showed no significant difference in terms of intraoperative variation of systolic blood pressure (P = 0.291), diastolic blood pressure (P = 0.737), heart rate (P = 0.107), peripheral oxygen saturation (P = 0.188), bispectral index (P = 0.158), and the occurrence of sedation-related adverse events including hypotension (P = 0.170) and hypoxemia (P = 0.423). CONCLUSION: The results suggest that a low-dose three-drug regimen consisting of midazolam, alfentanil, and propofol seems safe and effective for deep sedation of elderly and very elderly patients undergoing ERCP procedures. However, further studies are required to verify these findings and clarify the benefits and risks of this method.
Asunto(s)
Sedación Profunda , Propofol , Anciano , Persona de Mediana Edad , Humanos , Propofol/efectos adversos , Midazolam/efectos adversos , Alfentanilo/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colangiopancreatografia Retrógrada Endoscópica/métodos , Hipnóticos y Sedantes/efectos adversos , Sedación Profunda/efectos adversos , Sedación Profunda/métodos , Estudios Retrospectivos , Sedación Consciente/efectos adversos , Sedación Consciente/métodosRESUMEN
INTRODUCTION: The aims of this study were to investigate the independent risk factors associated with iatrogenic withdrawal syndrome in pediatric intensive care units (PICUs) and to establish receiver operator characteristic (ROC) curve to facilitate the diagnosis of iatrogenic withdrawal syndrome in clinical settings. METHODS: Pediatric patients who received analgesic and sedative medication at a tertiary hospital in the southern Zhejiang region of China between January 2016 and December 2022 were selected for the study. Clinical case data were retrospectively analyzed to gather information including age, gender, weight, total dose of analgesic and sedative medication, total treatment duration, average maintenance dose, and other relevant parameters. Medically induced withdrawal symptom scores were assessed using the Sophia Observation Scale for Withdrawal Symptoms (SOS). Univariate and multivariate logistic regression analyses were conducted on the above indicators to identify the risk factors for iatrogenic withdrawal, and an ROC curve was constructed. RESULTS: The study encompassed a total of 104 pediatric patients, comprising 47 patients in the SOS score ≥4 group and 57 patients in the SOS score ≤3 group. The incidence of iatrogenic withdrawal was 45.19%. Univariate analysis identified cumulative total dose of fentanyl, average daily dose of fentanyl, average daily dose of midazolam, and patient weight (p < 0.05) as factors associated with iatrogenic withdrawal syndrome. The logistic multiple regression analysis revealed that the average daily dose of fentanyl was an independent risk factor for the occurrence of iatrogenic withdrawal syndrome in critically ill children (p < 0.05). ROC curve analysis indicated an area under the curve of 0.711 (95% CI: 0.610-0.811) with sensitivity and specificity of 73.7% and 61.7%, respectively. CONCLUSION: The average daily maintenance dose of fentanyl holds significant clinical value in diagnosing and evaluating the prognosis of iatrogenic withdrawal syndrome and can provide a scientific foundation for enhancing sedative and analgesic management in clinical practice.
Asunto(s)
Fentanilo , Hipnóticos y Sedantes , Enfermedad Iatrogénica , Unidades de Cuidado Intensivo Pediátrico , Curva ROC , Síndrome de Abstinencia a Sustancias , Humanos , Estudios Retrospectivos , Masculino , Femenino , Factores de Riesgo , Síndrome de Abstinencia a Sustancias/diagnóstico , Síndrome de Abstinencia a Sustancias/epidemiología , Preescolar , Enfermedad Iatrogénica/epidemiología , Niño , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/administración & dosificación , Lactante , Fentanilo/efectos adversos , Fentanilo/administración & dosificación , Midazolam/efectos adversos , Midazolam/administración & dosificación , China/epidemiología , Adolescente , Analgésicos Opioides/efectos adversos , Analgésicos Opioides/administración & dosificaciónRESUMEN
INTRODUCTION: Periprocedural anxiety is common in pediatric patients and is characterized by tension, anxiety, irritability, and autonomic activation. Periprocedural anxiety increases during certain events including admission to the preoperative area, separation from caregivers, induction of anesthesia, and IV placement. A study of children aged 2-12 showed that perioperative anxiety in children may be influenced by high parental anxiety and low sociability of the child. While these are nonmodifiable variables in the perioperative setting, there are numerous ways to ameliorate both parental and patient anxiety including the use of certified child life specialists (CCLSs) to aid in child comfort. In this study, our objective was to evaluate the integration of CCLS in our perioperative setting on the rate of benzodiazepine use. METHODS: We used a prospectively maintained database to identify patients undergoing outpatient elective surgical and radiologic procedures from July 2022 to September 2023 and January 2023 to September 2023 respectively. CCLSs were used to work with appropriately aged children in order to decrease the use of benzodiazepines and reduce possible adverse events associated with their use. RESULTS: A total of 2175 pediatric patients were seen by CCLS in same day surgery from July 2022 to September 2023. During this period, midazolam use decreased by an average of 11.4% (range 6.2%-19.3%). An even greater effect was seen in the radiologic group with 73% reduction. No adverse events were reported during this period. CONCLUSIONS: CCLSs working with age-appropriate patients in the periprocedural setting is a useful adjunct in easing anxiety in pediatric patients, reducing the need for periprocedural benzodiazepine administration and the risk of exposure to unintended side effects.
Asunto(s)
Ansiedad , Benzodiazepinas , Humanos , Proyectos Piloto , Niño , Preescolar , Femenino , Masculino , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Ansiedad/prevención & control , Ansiedad/etiología , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Procedimientos Quirúrgicos Electivos/efectos adversos , Midazolam/administración & dosificación , Midazolam/efectos adversos , Estudios ProspectivosRESUMEN
Este metaanálisis investiga el impacto de midazolam intratecal en la anestesia espinal, el control del dolor postoperatorio y los efectos secundarios relacionados con la anestesia en la cirugía de miembros inferiores. Realizamos una búsqueda en Medline, Science Direct, Google Scholar y Cochrane Library de los estudios que reportaron el inicio y la duración de los bloqueos sensorial y motor, el tiempo transcurrido hasta la primera solicitud de analgesia, el consumo de opioides durante 24h, el control del dolor postoperatorio y los efectos secundarios tras la administración de midazolam intratecal en pacientes sometidos a cirugía de miembros inferiores. Se identificaron 10 estudios, que se incluyeron en el metaanálisis. La revisión fue realizada siguiendo las directrices PRISMA, registrándose en la base de datos PROSPERO (ID-CRD42022346361) en agosto de 2022. Nuestros resultados muestran que los pacientes que reciben 1mg de midazolam intratecal reflejaron un tiempo de inicio de bloqueo significativamente más alto (p=0,001 [IC: −0,98, −0,31]), mayor duración de los bloqueos sensorial y motor (p<0,00001 [IC: 18,08, 39,12]; p=0,002 [IC: 0,45, 2]), y mayor tiempo transcurrido hasta la primera solicitud de analgesia de rescate (p=0,0003 [IC: 1,22, 4,14]). Las puntuaciones de dolor a las 4 y 12h postoperatorias fueron significativamente inferiores en los pacientes que recibieron midazolam intratecal (p=0,00001 [: −1,20, −0,47] y p=0,05 [IC: −0,52, −0,01] respectivamente). En conclusión, la adición de midazolam intratecal al anestésico local en la cirugía de miembros inferiores acorta el tiempo de inicio de los bloqueos sensorial y motor, incrementa la duración del bloqueo y prolonga el tiempo transcurrido hasta la primera solicitud de analgesia. Las puntuaciones del dolor a las 4 y 12horas postoperatorias fueron menores, no observándose efectos secundarios adicionales.(AU)
This meta-analysis was done to investigate the role of intrathecal midazolam in lower limb surgeries regarding prolongation of spinal block, postoperative pain control and associated side effects. The included studies reported onset and duration of sensory and motor block, time to first request analgesia, 24hours opioid consumption, postoperative pain control, and associated side effects following use of intrathecal midazolam for lower limb surgeries. This review was performed following the PRISMA guidelines and using the online databases, Medline, Science Direct, Google scholar and Cochrane library. We registered this review with the PROSPERO database (ID-CRD42022346361) in August 2022. A total of 10 randomised controlled trials were included in this meta-analysis. Our results showed patients receiving 1mg intrathecal midazolam showed significantly faster onset of sensory block (P=.001 [CI: −0.98, −0.31]). Duration of sensory and motor block were also significantly prolonged in intrathecal midazolam group (P<.00001 [CI: 18.08, 39.12], P=.002 [CI: 0.45, 2]). Intrathecal midazolam also increased the time to first request analgesia (P=.0003 [CI: 1.22, 4.14]). Pain scores at 4 and 12hours postoperatively were significantly lower in patients receiving intrathecal midazolam (P=.00001[CI: −1.20, −0.47] and P=0.05 [CI: −0.52, −0.01] respectively). In conclusion, the addition of intrathecal midazolam to local anesthetics in lower limb surgeries results in early onset of sensory and motor block. It also increases the duration of sensory and motor block. The time to first request analgesia is increased. VAS pain scores at 4 and 12hours postoperatively were also lower without any increased side effects.(AU)
Asunto(s)
Humanos , Masculino , Femenino , Conducta Adictiva , Midazolam/efectos adversos , Dimensión del Dolor/métodos , Extremidad Inferior/cirugía , Dolor Postoperatorio/tratamiento farmacológico , Trastornos Relacionados con Opioides , Manejo del Dolor , Dolor/tratamiento farmacológico , Analgesia , AnestesiologíaRESUMEN
OBJECTIVE: This study aims to perform a meta-analysis to evaluate the safety and efficacy of dexmedetomidine versus midazolam for complex digestive endoscopy procedures, with the goal of offering comprehensive clinical evidence. METHODS: Following predefined inclusion criteria, five databases were systematically searched, with a focus on identifying randomized controlled trials (RCTs) that compared the administration of dexmedetomidine and midazolam during complex digestive endoscopy procedures. The statistical software Stata 15.1 was employed for meticulous data analysis. RESULTS: Sixteen RCTs were encompassed, involving a total of 1218 patients. In comparison to the midazolam group, dexmedetomidine administration was associated with a reduced risk of respiratory depression (RR=0.25, 95 %CI: 0.11-0.56) and hypoxemia (RR=0.22, 95 %CI: 0.12-0.39). Additionally, the dexmedetomidine group exhibited lower incidence rates of choking (RR=0.27, 95 %CI: 0.16-0.47), physical movement (RR=0.16, 95 %CI: 0.09-0.27), and postoperative nausea and vomiting (RR=0.56,95 %CI: 0.34-0.92). Patients and endoscopists in the dexmedetomidine group reported higher levels of satisfaction (patient satisfaction: SMD=0.73, 95 %CI: 0.26-1.21; endoscopist satisfaction: SMD=0.84, 95 %CI: 0.24-1.44). The incidence of hypotension and anesthesia recovery time did not significantly differ between the two groups (hypotension: RR=1.73,95 %CI:0.94-3.20; anesthesia recovery time: SMD=0.02, 95 %Cl: 0.44-0.49). It is noteworthy that the administration of dexmedetomidine was associated with a significant increase in the incidence of bradycardia in patients. CONCLUSION: Compared to midazolam, dexmedetomidine exhibits a favorable safety profile for use in complex gastrointestinal endoscopy by significantly reducing the risk of respiratory depression and hypoxemia. Despite this, dexmedetomidine is associated with a higher incidence of bradycardia. These findings underscore the need for further research through larger, multi-center studies to thoroughly investigate dexmedetomidine's safety and efficacy.
Asunto(s)
Dexmedetomidina , Endoscopía Gastrointestinal , Hipnóticos y Sedantes , Midazolam , Dexmedetomidina/efectos adversos , Dexmedetomidina/administración & dosificación , Dexmedetomidina/uso terapéutico , Humanos , Midazolam/administración & dosificación , Midazolam/efectos adversos , Endoscopía Gastrointestinal/efectos adversos , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/administración & dosificación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
AIM: Knowledge of risk factors may provide strategies to reduce the high burden of delirium in intensive care unit (ICU) patients. We aimed to compare the risk of delirium after deep sedation with propofol versus midazolam in ICU patients. METHODS: In this prospective cohort study, ICU patients who were in an unarousable state for ≥24 h due to continuous sedation with propofol and/or midazolam were included. Patients admitted ≤24 h, those with an acute neurological disorder and those receiving palliative sedation were excluded. ICU patients were assessed daily for delirium during the 7 days following an unarousable state due to continuous sedation. RESULTS: Among 950 included patients, 605 (64%) subjects were delirious during the 7 days after awaking. The proportion of subsequent delirium was higher after midazolam sedation (152/207 [73%] patients) and after both propofol and midazolam sedation (257/377 [68%] patients), compared to propofol sedation only (196/366 [54%] patients). Midazolam sedation (adjusted cause-specific hazard ratio [adj. cause-specific HR] 1.32, 95% confidence interval [CI] 1.05-1.66) and propofol and midazolam sedation (adj. cause-specific HR 1.29, 95% CI 1.06-1.56) were associated with a higher risk of subsequent delirium compared to propofol sedation only. CONCLUSION: This study among sedated ICU patients suggests that, compared to propofol sedation, midazolam sedation is associated with a higher risk of subsequent delirium. This risk seems more apparent in patients with high cumulative midazolam intravenous doses. Our findings underpin the recommendations of the Society of Critical Care Medicine Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) guidelines to use propofol over benzodiazepines for sedation in ICU patients.
Asunto(s)
Sedación Profunda , Delirio , Hipnóticos y Sedantes , Unidades de Cuidados Intensivos , Midazolam , Propofol , Humanos , Midazolam/efectos adversos , Midazolam/administración & dosificación , Propofol/efectos adversos , Propofol/administración & dosificación , Masculino , Femenino , Unidades de Cuidados Intensivos/estadística & datos numéricos , Persona de Mediana Edad , Hipnóticos y Sedantes/efectos adversos , Hipnóticos y Sedantes/administración & dosificación , Estudios Prospectivos , Anciano , Factores de Riesgo , Delirio/inducido químicamente , Delirio/prevención & control , Delirio/epidemiología , Sedación Profunda/efectos adversos , Sedación Profunda/métodos , AdultoRESUMEN
OBJECTIVE: To describe seizure activity in juvenile dogs successfully weaned from long-term mechanical ventilation. CASE SERIES SUMMARY: Three juvenile dogs (all approximately 3 months old) underwent long-term mechanical ventilation with IV anesthesia for suspected noncardiogenic pulmonary edema. Within 24 hours of extubation and within 10 hours of discontinuing midazolam continuous infusions, all dogs experienced seizures, which is 1 sign of iatrogenic withdrawal syndrome. Each dog was treated with an anticonvulsant protocol, and none experienced seizures after being discharged. NEW OR UNIQUE INFORMATION PROVIDED: Each dog received IV anesthesia, including fentanyl, dexmedetomidine, midazolam, and propofol, during mechanical ventilation and subsequently experienced seizures after successful weaning from mechanical ventilation. Juvenile dogs may be at risk for seizures after weaning from mechanical ventilation and IV anesthesia. Neurological monitoring and further research into an appropriate weaning protocol may prove beneficial in juvenile dogs requiring prolonged anesthesia.
Asunto(s)
Enfermedades de los Perros , Respiración Artificial , Perros , Animales , Respiración Artificial/veterinaria , Midazolam/efectos adversos , Desconexión del Ventilador/veterinaria , Desconexión del Ventilador/métodos , Anestésicos Intravenosos , Convulsiones/inducido químicamente , Convulsiones/veterinaria , Enfermedad Iatrogénica/veterinaria , Enfermedades de los Perros/inducido químicamenteRESUMEN
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.
Asunto(s)
Trastorno Depresivo Mayor , Trastorno Depresivo Resistente al Tratamiento , Ketamina , Adulto , Humanos , Ketamina/efectos adversos , Midazolam/efectos adversos , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/psicología , Método Doble Ciego , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Trastorno Depresivo Resistente al Tratamiento/psicología , Cognición , Resultado del TratamientoRESUMEN
INTRODUCTION: Pulsed field ablation (PFA) represents a novel, nonthermal energy modality that can be applied for single-shot pulmonary vein isolation (PVI) in atrial fibrillation (AF). Comparative data with regard to deep sedation to established single-shot modalities such as cryoballoon (CB) ablation are scarce. The aim of this study was to compare a deep sedation protocol in patients receiving PVI with either PFA or CB. METHODS: Prospective, consecutive AF patients undergoing PVI with a pentaspline PFA catheter were compared to a retrospective CB-PVI cohort of the same timeframe. Study endpoints were the requirements of analgesics, cardiorespiratory stability, and sedation-associated complications. RESULTS: A total of 100 PVI patients were included (PFA n = 50, CB n = 50, mean age 66 ± 10.6, 61% male patients, 65% paroxysmal AF). Requirement of propofol, midazolam, and sufentanyl was significantly higher in the PFA group compared to CB [propofol 0.14 ± 0.04 mg/kg/min in PFA vs. 0.11 ± 0.04 mg/kg/min in CB (p = .001); midazolam 0.00086 ± 0.0004 mg/kg/min in PFA vs. 0.0006295 ± 0.0003 mg/kg/min in CB (p = .002) and sufentanyl 0.0013 ± 0.0007 µg/kg/min in PFA vs. 0.0008 ± 0.0004 µg/kg/min in CB (p < .0001)]. Sedation-associated complications did not differ between both groups (PFA n = 1/50 mild aspiration pneumonia, CB n = 0/50, p > .99). Nonsedation-associated complications (PFA: n = 2/50, 4%, CB: n = 1/50, 2%, p > .99) and procedure times (PFA 75 ± 31, CB 84 ± 32 min, p = .18) did not differ between groups. CONCLUSIONS: PFA is associated with higher sedation and especially analgesia requirements. However, the safety of deep sedation does not differ to CB ablation.
Asunto(s)
Analgesia , Fibrilación Atrial , Criocirugía , Propofol , Humanos , Masculino , Persona de Mediana Edad , Anciano , Femenino , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/cirugía , Estudios Retrospectivos , Estudios Prospectivos , Midazolam/efectos adversos , Criocirugía/efectos adversos , Criocirugía/métodosRESUMEN
BACKGROUND: Dexmedetomidine sedation has advantages, such as low incidence of respiratory depression and prolonged block duration, but also significant disadvantages, such as slow onset, high rate of sedation failure, and a long context-sensitive half-life. Remimazolam provides rapid sedation and recovery, high sedation efficacy and has minimal hemodynamic effects. We hypothesized that patients who received remimazolam would require less rescue midazolam than dexmedetomidine. METHODS: Patients (n=103) scheduled for surgery under spinal anesthesia were randomized to receive dexmedetomidine (DEX group) or remimazolam (RMZ group) targeting a Modified Observer's Assessment of Alertness/Sedation score of 3 or 4. Rescue midazolam was administered if the patient failed to be sedated after the initial loading dose or despite infusion rate adjustment. RESULTS: Rescue midazolam administration was significantly higher in the DEX group (0% vs 39.2%; p<0.001). Patients in the RMZ group reached the target sedation level more rapidly. The incidences of bradycardia (0% vs 25.5%; p<0.001) and hypertension (0% vs 21.6%; p<0.001) were higher in the DEX group. Respiratory depression occurred at a higher rate in the RMZ group (21.2% vs 2.0%; p=0.002), but no patients required manual ventilation. Patients in the RMZ group recovered faster, had a shorter PACU stay and higher satisfaction scores. Hypotensive episodes in the PACU were more frequent in the DEX group (1.9% vs 29.4%; p<0.001). CONCLUSIONS: Remimazolam showed excellent sedation efficacy, minimal hemodynamic effects, and fewer adverse events in the PACU than dexmedetomidine. However, it is important to note that respiratory depression was more frequent with the use of remimazolam. TRIAL REGISTRATION NUMBER: NCT05447507.
Asunto(s)
Anestesia Raquidea , Benzodiazepinas , Dexmedetomidina , Insuficiencia Respiratoria , Humanos , Midazolam/efectos adversos , Hipnóticos y Sedantes/efectos adversos , Dexmedetomidina/efectos adversos , Anestesia Raquidea/efectos adversos , Insuficiencia Respiratoria/inducido químicamente , Insuficiencia Respiratoria/diagnóstico , Insuficiencia Respiratoria/prevención & control , Extremidad Inferior/cirugíaRESUMEN
Importance: The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use. Objective: To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020. Interventions: Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction. Main Outcomes and Measures: The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively. Results: Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group. Conclusion and Relevance: A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03052660.
Asunto(s)
Midazolam , Satisfacción del Paciente , Anciano , Humanos , Masculino , Femenino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Método Doble Ciego , Anestesia General , Satisfacción Personal , Atención Dirigida al PacienteRESUMEN
STUDY OBJECTIVE: To evaluate the association between midazolam premedication and postoperative delirium in a large retrospective cohort of patients ≥70 years. DESIGN: Retrospective cohort study. SETTING: A single tertiary academic medical center. PATIENTS: Patients ≥70 years having elective non-cardiac surgery under general anesthesia from 2020 to 2021. INTERVENTIONS: Midazolam premedication, defined as intravenous midazolam administration prior to induction of general anesthesia. MEASUREMENTS: The primary outcome, postoperative delirium, was a collapsed composite outcome including at least one of the following: a positive 4A's test during post-anesthesia care unit stay and/or the initial 2 postoperative days; physician or nursing records reporting new-onset confusion as captured by the CHART-DEL instrument; or a positive 3D-CAM test. The association between midazolam premedication and postoperative delirium was assessed using multivariable logistic regression, adjusting for potential confounding variables. As secondary analysis, we investigated the association between midazolam premedication and a composite of other postoperative complications. Several sensitivity analyses were performed using similar regression models. MAIN RESULTS: In total, 1973 patients were analyzed (median age 75 years, 47% women, 50% ASA score ≥ 3, 32% high risk surgery). The overall incidence of postoperative delirium was 15.3% (302/1973). Midazolam premedication was administered to 782 (40%) patients (median [IQR] dose 2 [1,2] mg). After adjustment for potential confounding variables, midazolam premedication was not associated with increased odds of postoperative delirium, with adjusted odds ratio of 1.09 (95% confidence interval 0.82-1.45; P = 0.538). Midazolam premedication was also not associated with the composite of other postoperative complications. Furthermore, no association was found between midazolam premedication and postoperative delirium in any of the sensitivity analyses preformed. CONCLUSIONS: Our results suggest that low doses of midazolam can be safely used to pre-medicate elective surgical patients 70 years or older before non-cardiac surgery, without significant effect on the risk of developing postoperative delirium.
Asunto(s)
Delirio del Despertar , Midazolam , Humanos , Femenino , Anciano , Masculino , Midazolam/efectos adversos , Delirio del Despertar/epidemiología , Delirio del Despertar/prevención & control , Delirio del Despertar/inducido químicamente , Estudios Retrospectivos , Premedicación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & controlRESUMEN
BACKGROUND: Prior trials suggest that intravenous racemic ketamine is a highly effective for treatment-resistant depression (TRD), but phase 3 trials of racemic ketamine are needed. AIMS: To assess the acute efficacy and safety of a 4-week course of subcutaneous racemic ketamine in participants with TRD. Trial registration: ACTRN12616001096448 at www.anzctr.org.au. METHOD: This phase 3, double-blind, randomised, active-controlled multicentre trial was conducted at seven mood disorders centres in Australia and New Zealand. Participants received twice-weekly subcutaneous racemic ketamine or midazolam for 4 weeks. Initially, the trial tested fixed-dose ketamine 0.5 mg/kg versus midazolam 0.025 mg/kg (cohort 1). Dosing was revised, after a Data Safety Monitoring Board recommendation, to flexible-dose ketamine 0.5-0.9 mg/kg or midazolam 0.025-0.045 mg/kg, with response-guided dosing increments (cohort 2). The primary outcome was remission (Montgomery-Åsberg Rating Scale for Depression score ≤10) at the end of week 4. RESULTS: The final analysis (those who received at least one treatment) comprised 68 in cohort 1 (fixed-dose), 106 in cohort 2 (flexible-dose). Ketamine was more efficacious than midazolam in cohort 2 (remission rate 19.6% v. 2.0%; OR = 12.1, 95% CI 2.1-69.2, P = 0.005), but not different in cohort 1 (remission rate 6.3% v. 8.8%; OR = 1.3, 95% CI 0.2-8.2, P = 0.76). Ketamine was well tolerated. Acute adverse effects (psychotomimetic, blood pressure increases) resolved within 2 h. CONCLUSIONS: Adequately dosed subcutaneous racemic ketamine was efficacious and safe in treating TRD over a 4-week treatment period. The subcutaneous route is practical and feasible.
Asunto(s)
Trastorno Depresivo Resistente al Tratamiento , Ketamina , Humanos , Ketamina/efectos adversos , Depresión , Midazolam/efectos adversos , Australia , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológicoRESUMEN
There is a rising number in complications associated with more cardiac electrical devices implanted (CIED). Infection and lead dysfunction are reasons to perform transvenous lead extraction. An ideal anaesthetic approach has not been described yet. Most centres use general anaesthesia, but there is a lack in studies looking into deep sedation (DS) as an anaesthetic approach. We report our retrospective experience for a large number of procedures performed with deep sedation as a primary approach. Extraction procedures performed between 2011 and 2018 in our electrophysiology laboratory have been included retrospectively. We began by applying a bolus injection of piritramide followed by midazolam as primary medication and would add etomidate if necessary. For extraction of leads a stepwise approach with careful traction, locking stylets, dilator sheaths, mechanical rotating sheaths and if needed snares and baskets has been used. A total of 780 leads in 463 patients (age 69.9 ± 12.3, 31.3% female) were extracted. Deep sedation was successful in 97.8% of patients. Piritramide was used as the main analgesic medication (98.5%) and midazolam as the main sedative (94.2%). Additional etomidate was administered in 15.1% of cases. In 2.2% of patients a conversion to general anaesthesia was required as adequate level of DS was not achieved before starting the procedure. Sedation related complications occurred in 1.1% (n = 5) of patients without sequalae. Deep sedation with piritramide, midazolam and if needed additional etomidate is a safe and feasible strategy for transvenous lead extraction.
Asunto(s)
Anestésicos , Sedación Profunda , Desfibriladores Implantables , Etomidato , Marcapaso Artificial , Humanos , Femenino , Masculino , Midazolam/efectos adversos , Estudios Retrospectivos , Pirinitramida , Sedación Profunda/efectos adversos , Sedación Profunda/métodos , Remoción de Dispositivos/efectos adversos , Remoción de Dispositivos/métodos , Resultado del Tratamiento , Marcapaso Artificial/efectos adversosRESUMEN
Purpose: To examine the influence of substituting intranasal (IN) midazolam (MID) for oral (PO) MID, within the three-drug combination of meperidine (MEP), hydroxyzine (H) and MID, on sedation treatment outcomes. Methods: A retrospective, cross-sectional analysis examined patient variables and sedation outcomes in 508 pediatric dental patients sedated by single- and multi-drug sedation regimens (MEP-H; MEP-H-(PO)-MID; MEP-H-(IN)-MID; single-agent MID). The outcome assessment examined sedation visit effectiveness, sedation treatment completion, treatment time and medication administration to discharge time. Multivariable logistic regression analyses assessed predictive variables associated with sedation visit effectiveness. Results: Both three-drug combinations (MEP-H-(PO)-MID; MEP-H-(IN)-MID) were used for behavior guidance in children of a similar age (median age=7.1 and 6.5 years, respectively, for the two drug combinations) and weight (median weight = 23.7 and 23.5 kg, respectively, for the two drug combinations). These three-drug combinations had a higher likelihood of sedation effectiveness over the reference sedation regimen of single-agent midazolam (MEP-H-(PO)-MID adjusted odds ratio [OR] = 2.65; 95 percent confidence interval [95% CI]=1.09 to 6.45; P=0.032; and MEP-H-(IN)-MID OR=2.08; 95% CI=1.03 to 4.18; P=0.039). MEP-H-(IN)MID was associated with a shorter medication administration to discharge time for patients by 23 minutes (interquartile range [IQR]=9.5 to 34 minutes) compared to MEP-H-(PO) MID (P<0.05) while providing a comparable number of teeth treated (median=five). All sedation drug regimens, including MEP-H-(IN)MID, had high levels of oxygen saturation during all sedation appointments. Conclusion: Substituting IN for PO MID in MEP-H-MID was associated with a shorter total time to discharge while demonstrating comparable efficacy during sedation.