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1.
Minerva Anestesiol ; 90(10): 901-911, 2024 10.
Artículo en Inglés | MEDLINE | ID: mdl-39101304

RESUMEN

INTRODUCTION: The need for safe anesthetic agents with minimal side effects has led to the development of remimazolam, a new benzodiazepine designed to be an alternative to the commonly used drug propofol, which has significant hemodynamic effects. This study aims to compare the hemodynamic effects of remimazolam with propofol during general anesthesia. EVIDENCE ACQUISITION: A systematic search was conducted in Embase, Web of Science, Cochrane Library, Scopus, and PubMed databases on 13/02/2023, following the recommendations of Cochrane Handbook and the PRISMA statement. The measure of association used was Risk Ratio (RR) or standardized mean difference, with 95% confidence intervals (CI) and 95% Prediction intervals (PI). An additional search was conducted on 04/09/2023. A Trial Sequential Analysis and a GRADE (Grading of Recommendations Assessment, Development and Evaluation) evidence table were conducted based on the editor's recommendation. EVIDENCE SYNTHESIS: After applying eligibility criteria and removing duplicates, 16 randomized clinical trials comprising 1951 patients were included in the meta-analysis. Significant associations favoring remimazolam over propofol were observed in the following aspects: intraoperative hypotension events (RR=0.47; 95% CI=0.41 to 0.54; 95% PI=0.40 to 0.55); frequency of vasoactive drug administration (RR=0.54; 95% CI=0.46 to 0.64; 95% PI=0.41 to 0.74); intraoperative bradycardia (RR=0.39; 95% CI=0.27 to 0.57; 95% PI=0.26 to 0.66); mean arterial pressure at induction (MD=7.77; 95% CI=6.00 to 9.55; 95% PI=4.39 to 11.15); heart rate at induction (MD=6.40; 95% CI=4.07 to 8.73; 95% PI=0.33 to 12.48); and heart rate at intubation (MD=6.06; 95% CI=2.33 to 9.78; 95% PI=-5.59 to 17.71). CONCLUSIONS: This study provides evidence that remimazolam induces fewer cardiorespiratory depressant effects and has a more favorable side effect profile compared to propofol during general anaesthesia.


Asunto(s)
Anestesia General , Benzodiazepinas , Hemodinámica , Propofol , Humanos , Anestesia General/efectos adversos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Hemodinámica/efectos de los fármacos , Propofol/administración & dosificación , Propofol/efectos adversos
2.
Minerva Anestesiol ; 90(9): 775-784, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38775443

RESUMEN

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.


Asunto(s)
Benzodiazepinas , Endoscopía Gastrointestinal , Hipnóticos y Sedantes , Propofol , Anciano , Humanos , Benzodiazepinas/administración & dosificación , Benzodiazepinas/efectos adversos , Sedación Consciente/métodos , Sedación Consciente/efectos adversos , Endoscopía Gastrointestinal/efectos adversos , Endoscopía Gastrointestinal/métodos , Endoscopía Gastrointestinal/psicología , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Propofol/administración & dosificación , Propofol/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto
3.
Braz J Anesthesiol ; 74(4): 844503, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38641324

RESUMEN

BACKGROUND: The incidence of arterial hypotension during induction of general anesthesia is influenced by the method of propofol administration, but there is a dearth of randomized clinical trials comparing bolus injection and target-controlled infusion in relation to arterial hypotension. This study seeks to compare the incidence of arterial hypotension between these two methods of propofol administration. METHODS: This prospective, randomized, single-center, non-blinded study included 60 patients (aged 35 to 55 years), classified as ASA physical status I or II, who were undergoing non-cardiac surgeries. They were randomly allocated using a computer to two groups based on the method of propofol administration during the induction of general anesthesia: the Target Group, receiving target-controlled infusion at 4 µg.mL-1, and the Bolus Group, receiving a bolus infusion of 2 mg.kg-1. Both groups also received midazolam 2 mg, fentanyl 3 µg.kg-1, and rocuronium 0.6 mg.kg-1. Over the first 10 minutes of anesthesia induction, Mean Arterial Pressure (MAP), Heart Rate (HR), level of Consciousness (qCON), and Suppression Rate (SR) were recorded every 2 minutes. RESULTS: Twenty-seven patients remained in the TCI group, while 28 were in the Bolus group. Repeated measure analysis using mixed-effects models could not reject the null hypothesis for the effect of group-time interactions in MAP (p = 0.85), HR (p = 0.49), SR (p = 0.44), or qCON (p = 0.72). The difference in means for qCON (60.2 for TCI, 50.5 for bolus, p < 0.001), MAP (90.3 for TCI, 86.2 for bolus, p < 0.006), HR (76.2 for TCI, 76.9 for bolus, p = 0.93), and SR (0.01 for TCI, 5.5 for bolus, p < 0.001), irrespective of time (whole period means), revealed some significant differences. CONCLUSION: Patients who received propofol bolus injection exhibited a lower mean arterial pressure, a greater variation in the level of consciousness, and a higher suppression rate compared to those who received it as a target-controlled infusion. However, the interaction effect between groups and time remains inconclusive.


Asunto(s)
Anestesia General , Anestésicos Intravenosos , Hipotensión , Propofol , Humanos , Propofol/administración & dosificación , Propofol/efectos adversos , Adulto , Persona de Mediana Edad , Anestesia General/métodos , Femenino , Masculino , Hipotensión/epidemiología , Hipotensión/inducido químicamente , Estudios Prospectivos , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Infusiones Intravenosas , Incidencia , Inyecciones Intravenosas , Presión Arterial/efectos de los fármacos
4.
J Pediatr Gastroenterol Nutr ; 76(5): 667-671, 2023 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-36821854

RESUMEN

OBJECTIVES: Pediatric patients undergoing esophagogastroduodenoscopy (EGD) commonly receive procedural sedation for comfort and to facilitate the procedure. EGD with procedural sedation carries the risk of several airway incidents and/or adverse events (AIAE). Topical pharyngeal anesthetics (TPAs) can blunt the airway reflexes and decrease the incidence of laryngospasm but has not been well studied with EGD under procedural sedation. We aimed to study the effect of adding a TPA to propofol-based sedation on the rate of AIAE. METHODS: This is a single-center, retrospective, observational cohort study. We compare AIAE rates (coughing, gagging, apnea, airway obstruction, and laryngospasm) in children who received TPA as part of their propofol-based procedural sedation for EGD with those who did not receive TPA. RESULTS: In 2021, 73 patients received TPA as part of the procedural sedation for EGD and 123 did not. The overall rate of AIAE was high with 75 (38%) patients experiencing 1 or more AIAE. Patients who received benzocaine spray experienced more AIAE than the control group [adjusted odds ratio (aOR) = 1.16; 95% confidence interval (CI): 1.01-1.34; P = 0.037]. Coughing, gagging, apnea with desaturation rates, and laryngospasm were similar in both groups (coughing aOR = 1.01; 95% CI: 0.91-1.13; P = 0.814; gagging aOR = 1.01; 95% CI: 0.91-1.13; P = 0.814; apnea aOR = 0.99; 95% CI: 0.95-1.04; P = 0.688; laryngospasm OR = 1.01; 95% CI: 0.95-1.07; P = 0.71). The rate of airway obstruction requiring jaw thrust was higher in the benzocaine group but did not reach statistical significance (aOR = 1.11; 95% CI: 0.97-1.26; P = 0.133). CONCLUSION: The use of topical pharyngeal benzocaine in children undergoing EGD with propofol-based sedation is associated with a higher overall AIAE rate. Most of the AIAE were mild incidents and only 7 patients experienced true adverse events.


Asunto(s)
Obstrucción de las Vías Aéreas , Anestesia , Laringismo , Propofol , Humanos , Niño , Propofol/efectos adversos , Benzocaína , Laringismo/prevención & control , Laringismo/inducido químicamente , Estudios Retrospectivos , Atragantamiento , Apnea/inducido químicamente , Endoscopía del Sistema Digestivo/métodos , Anestesia/métodos , Obstrucción de las Vías Aéreas/inducido químicamente , Sedación Consciente , Hipnóticos y Sedantes
7.
Basic Clin Pharmacol Toxicol ; 130(2): 277-287, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34825477

RESUMEN

Anaesthesia with propofol is frequently associated with hypotension, which is at least partially attributable to increased nitric oxide (NO) formation derived from the activation of protein kinase C (PKC)/endothelial NO synthase (NOS3) axis. In this cross-sectional study, we tested whether PRKCA (which encodes PKCα) polymorphisms, or haplotypes, and interactions among PRKCA and NOS3 polymorphisms affect the hypotensive responses to propofol. We collected venous blood samples from 164 patients before and 10 min after propofol administration. Genotypes were determined by PCR and haplotype frequencies were estimated. Nitrite and NOx (nitrites+nitrates) levels were measured by using an ozone-based chemiluminescence assay and the Griess reaction, respectively. We used multifactor dimensionality reduction to test interactions among PRKCA and NOS3 polymorphisms. Propofol promoted enhanced blood pressure-lowering effects and increased nitrite levels in subjects carrying GA + AA genotypes for the rs16960228 and TC + CC genotypes for the rs1010544 PRKCA polymorphisms, and the CCG haplotype. Moreover, genotypes for the rs1010544 PRKCA polymorphism were associated with higher or lower blood pressure decreases in response to propofol depending on the genotypes for the rs2070744 NOS3 polymorphism. Our findings suggest that PRKCA genotypes and haplotypes impact the hypotensive responses to propofol, possibly by modifying NO bioavailability, and that PRKCA-NOS3 interactions modify the blood pressure-lowering effects of propofol.


Asunto(s)
Hipotensión/inducido químicamente , Óxido Nítrico Sintasa de Tipo III/genética , Propofol/efectos adversos , Proteína Quinasa C-alfa/genética , Adulto , Anciano , Anestésicos Intravenosos/administración & dosificación , Anestésicos Intravenosos/efectos adversos , Estudios Transversales , Femenino , Genotipo , Haplotipos , Humanos , Hipotensión/genética , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Propofol/administración & dosificación
8.
Sci Rep ; 11(1): 23133, 2021 11 30.
Artículo en Inglés | MEDLINE | ID: mdl-34848804

RESUMEN

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.


Asunto(s)
Encéfalo/efectos de los fármacos , Dexmedetomidina/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Pulmón/efectos de los fármacos , Propofol/administración & dosificación , Animales , Isquemia Encefálica/prevención & control , Dexmedetomidina/efectos adversos , Modelos Animales de Enfermedad , Células Endoteliales/efectos de los fármacos , Hipnóticos y Sedantes/efectos adversos , Interleucina-1beta/biosíntesis , Interleucina-6/biosíntesis , Macrófagos Alveolares/efectos de los fármacos , Masculino , Propofol/efectos adversos , Ratas , Ratas Wistar , Tiopental , Factor de Necrosis Tumoral alfa/biosíntesis , Molécula 1 de Adhesión Celular Vascular/biosíntesis
9.
Eur J Clin Pharmacol ; 77(6): 869-877, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33410970

RESUMEN

PURPOSE: Propofol anesthesia is usually accompanied by hypotensive responses, which are at least in part mediated by nitric oxide (NO). Arginase I (ARG1) and arginase II (ARG2) compete with NO synthases for their common substrate L-arginine, therefore influencing the NO formation. We examined here whether ARG1 and ARG2 genotypes and haplotypes affect the changes in blood pressure and NO bioavailability in response to propofol. METHODS: Venous blood samples were collected from 167 patients at baseline and after 10 min of anesthesia with propofol. Genotypes were determined by polymerase chain reaction. Nitrite concentrations were measured by using an ozone-based chemiluminescence assay, while NOx (nitrites + nitrates) levels were determined by using the Griess reaction. RESULTS: We found that patients carrying the AG + GG genotypes for the rs3742879 polymorphism in ARG2 gene and the ARG2 GC haplotype show lower increases in nitrite levels and lower decreases in blood pressure after propofol anesthesia. On the other hand, subjects carrying the variant genotypes for the rs10483801 polymorphism in ARG2 gene show more intense decreases in blood pressure (CA genotype) and/or higher increases in nitrite levels (CA and AA genotypes) in response to propofol. CONCLUSION: Our results suggest that ARG2 variants affect the hypotensive responses to propofol, possibly by modifying NO bioavailability. TRIAL REGISTRATION: NCT02442232.


Asunto(s)
Anestésicos Intravenosos/efectos adversos , Arginasa/genética , Hipotensión/inducido químicamente , Óxido Nítrico/metabolismo , Propofol/efectos adversos , Adulto , Anciano , Anestésicos Intravenosos/farmacocinética , Femenino , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Nitratos/sangre , Nitritos/sangre , Reacción en Cadena de la Polimerasa , Polimorfismo de Nucleótido Simple , Propofol/farmacocinética
10.
J Vasc Surg Venous Lymphat Disord ; 9(3): 621-626, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-32858244

RESUMEN

OBJECTIVE: Catheter-directed interventions (CDIs) have been increasingly used for selected patients with acute intermediate-risk (submassive) pulmonary embolism (sPE) to prevent decompensation, mortality, and potentially long-term sequelae. The purpose of the present study was to determine whether the choice of anesthetic during these interventions has an effect on the postprocedural outcomes. METHODS: Patients who had undergone CDI for acute sPE from 2009 to 2019 were identified and grouped according to the intraprocedural use of propofol. The primary outcome was in-hospital intra- or postprocedural major adverse events, defined as the need for intubation, progression to massive pulmonary embolism, and in-hospital death. Major bleeding events (ie, intracerebral hemorrhage, transfusion of ≥2 U, the need for reintervention) were also assessed. Multivariate logistic regression analysis was used to evaluate the predictors of the studied outcomes. RESULTS: During the study period, 340 patients (age, 58.74 ± 15.22 years; 51.2% men) had undergone CDI for sPE (85 standard thrombolysis, 229 ultrasound-assisted thrombolysis, 26 suction thrombectomy). Propofol had been used for 36 patients (10.6%); the remaining 304 patients (89.4%) had received midazolam plus fentanyl, morphine, or hydromorphone for anesthesia. The baseline characteristics of both groups were similar, except for age, hypertension, American Society of Anesthesiologists class, and procedure type, with ultrasound-assisted thrombolysis the predominant procedure for the no-propofol group (74%). Overall, 18 patients had experienced ≥1 events of the composite outcome (ie, 10 intubations, 11 decompensations, 2 surgical conversions, 3 deaths). The propofol group had a significantly greater adverse event rate (13.8%; n = 5) compared with the no-propofol group (4.2%; n = 13; P = .015). On multivariate analysis, propofol was still a predictive factor for adverse events (odds ratio, 3.79; 95% confidence interval, 1.11-12.93; P = .03). A total of 16 patients had experienced major bleeding or other procedure-related events, including stroke in 4 (1.17%), coronary sinus perforation in 1, tricuspid valve rupture in 1, and the need for transfusion in 10 patients. The type of intervention (ie, standard thrombolysis, ultrasound-assisted thrombolysis, suction thrombectomy) was not a predictive factor for any studied outcome. CONCLUSIONS: CDIs are low-risk procedures with minimal postoperative morbidity and mortality in the setting of acute sPE. However, the use of propofol for intraprocedural sedation should be avoided because it can have detrimental effects.


Asunto(s)
Anestésicos Intravenosos/efectos adversos , Propofol/efectos adversos , Embolia Pulmonar/terapia , Trombectomía/efectos adversos , Terapia Trombolítica/efectos adversos , Adulto , Anciano , Anestésicos Intravenosos/administración & dosificación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propofol/administración & dosificación , Embolia Pulmonar/diagnóstico por imagen , Embolia Pulmonar/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Trombectomía/mortalidad , Terapia Trombolítica/mortalidad , Factores de Tiempo , Resultado del Tratamiento
11.
BMC Anesthesiol ; 20(1): 195, 2020 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-32778055

RESUMEN

BACKGROUND: Propofol sedation is effective for gastrointestinal endoscopic procedures, but its narrow therapeutic window highlights the importance of identifying an optimal administration technique regarding effectiveness and safety. This study aimed to determine the incidence of significant adverse events in adult patients scheduled for gastrointestinal endoscopy under anaesthetist-performed sedation using propofol target-controlled infusion and determine the existence of associations between these events and potentially related variables. METHODS: This single-centre, retrospective cohort study took place in a tertiary referral university hospital. Medical records of 823 patients (age > 18 years, American Society of Anesthesiologists physical status classification scores I-III) who had undergone elective gastrointestinal endoscopy under propofol target-controlled infusion sedation during September 2018 were reviewed. Outcomes included hypoxia, hypotension, and bradycardia events, requirement of vasoactive drugs, unplanned tracheal intubation or supraglottic device insertion, and need for advanced cardiac life support. RESULTS: The most frequently encountered adverse event was oxygen desaturation < 95% with an incidence of 22.35%. Vasoactive drug administration, hypotension, and oxygen desaturation < 90% followed, with incidences of 19.2, 12.64, and 9.92%, respectively. Only 0.5% of patients required advanced airway management. Multivariate analysis revealed an association between hypotension events, colonoscopic procedures, and propofol doses (odds ratio: 3.08, 95% confidence interval: 1.43 to 6.61; P = 0.004 and odds ratio: 1.14, 95% confidence interval: 1.00 to 1.29; P = 0.046). A strong dose-effect relationship was found between hypoxia and obesity; patients with body mass index ≥40 were nine times (odds ratio: 10.22, 95% confidence interval: 2.83 to 36.99) more likely to experience oxygen desaturation < 90% events. CONCLUSIONS: Propofol sedation using target-controlled infusion appears to be a safe and effective anaesthetic technique for gastrointestinal endoscopic procedures with acceptable rates of adverse events and could be more widely adopted in clinical practice.


Asunto(s)
Anestésicos Intravenosos/administración & dosificación , Sedación Profunda/métodos , Sistemas de Liberación de Medicamentos/métodos , Endoscopía Gastrointestinal/métodos , Propofol/administración & dosificación , Anciano , Anestésicos Intravenosos/efectos adversos , Estudios de Cohortes , Endoscopía Gastrointestinal/efectos adversos , Femenino , Humanos , Hipotensión/inducido químicamente , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/prevención & control , Propofol/efectos adversos , Estudios Retrospectivos
12.
Rev Gaucha Enferm ; 41: e20190068, 2020.
Artículo en Portugués, Inglés | MEDLINE | ID: mdl-32348421

RESUMEN

OBJECTIVE: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. METHOD: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. RESULTS: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. CONCLUSION: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.


Asunto(s)
Analgésicos/efectos adversos , Cuidados Críticos/estadística & datos numéricos , Delirio/epidemiología , Hipnóticos y Sedantes/efectos adversos , Analgésicos/administración & dosificación , Distribución de Chi-Cuadrado , Clonidina/administración & dosificación , Clonidina/efectos adversos , Estudios Transversales , Delirio/inducido químicamente , Femenino , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Humanos , Hipnóticos y Sedantes/administración & dosificación , Unidades de Cuidados Intensivos , Masculino , Midazolam/administración & dosificación , Midazolam/efectos adversos , Midazolam/uso terapéutico , Persona de Mediana Edad , Prevalencia , Propofol/administración & dosificación , Propofol/efectos adversos
13.
J Crit Care ; 56: 281-287, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32001426

RESUMEN

Oxidative stress exacerbates brain damage following ischemia-reperfusion and traumatic brain injury (TBI). Management of TBI and critically ill patients commonly involves use of propofol, a sedation medication that acts as a general anesthetic with inherent antioxidant properties. Here we review available evidence from animal model systems and clinical studies that propofol protects against ischemia-reperfusion injury. However, evidence of propofol toxicity in humans exists and manifests as a rare complication, "propofol infusion syndrome" (PRIS). Evidence in animal models suggests that brain injury induces expression of the p75 neurotrophin receptor (p75NTR), which is associated with proapoptotic signaling. p75NTR-mediated apoptosis of neurons is further exacerbated by propofol's superinduction of p75NTR and concomitant inhibition of neurotrophin processing. Propofol is toxic to neurons but not astrocytes, a type of glial cell. Evidence suggests that propofol protects astrocytes from oxidative stress and stimulates astroglial-mediated protection of neurons. One may speculate that in brain injury patients under sedation/anesthesia, propofol provides brain tissue protection or aids in recovery by enhancing astrocyte function. Nevertheless, our understanding of neurologic recovery versus long-term neurological sequelae leading to neurodegeneration is poor, and it is also conceivable that propofol plays a partial as yet unrecognized role in long-term impairment of the injured brain.


Asunto(s)
Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Estrés Oxidativo , Propofol/efectos adversos , Propofol/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Anestesia , Anestésicos , Animales , Apoptosis , Astrocitos/efectos de los fármacos , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Humanos
14.
J Clin Sleep Med ; 16(5): 725-732, 2020 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-32029070

RESUMEN

STUDY OBJECTIVES: Drug-induced sleep endoscopy (DISE) using propofol is commonly used to identify the pharyngeal structure involved in collapse among patients with obstructive sleep apnea. DISE has never been compared with zolpidem-induced sleep endoscopy. We hypothesized that propofol at recommended sedation levels does not influence upper airway collapsibility nor the frequency of multilevel pharyngeal collapse as compared with zolpidem-induced sleep. METHODS: Twenty-one patients with obstructive sleep apnea underwent polysomnography and sleep endoscopy during zolpidem-induced sleep and during DISE with propofol. A propofol target-controlled infusion was titrated to achieve a bispectral index between 50 and 70. Airway collapsibility was estimated and compared in both conditions by peak inspiratory flow and the magnitude of negative effort dependence. Respiratory drive was estimated by the difference between end-expiratory and peak-negative inspiratory pharyngeal pressure (driving pressure). Site and configuration of pharyngeal collapse during zolpidem-induced sleep and DISE with propofol were compared. RESULTS: The frequency of multilevel collapse during zolpidem-induced sleep was similar to that observed during DISE with propofol (72% vs 86%, respectively; difference: 14%; 95% confidence interval: -12% to 40%; P = .453). The endoscopic classification of pharyngeal collapse during both conditions were similar. Peak inspiratory flow, respiratory drive (effect size: 0.05 and 0.03, respectively), and negative effort dependence (difference: -6%; 95% confidence interval: -16% to 4%) were also similar in both procedures. CONCLUSIONS: In this pilot study, recommended propofol doses did not significantly increase multilevel pharyngeal collapse or affect upper airway collapsibility and respiratory drive as compared with zolpidem-induced sleep. CLINICAL TRIAL REGISTRATION: Registry: clinicaltrials.gov; Name: Natural and Drug Sleep Endoscopy; URL: https://clinicaltrials.gov/ct2/show/study/NCT03004014; Identifier: NCT03004014.


Asunto(s)
Obstrucción de las Vías Aéreas , Propofol , Apnea Obstructiva del Sueño , Obstrucción de las Vías Aéreas/inducido químicamente , Endoscopía , Humanos , Proyectos Piloto , Propofol/efectos adversos , Sueño , Apnea Obstructiva del Sueño/inducido químicamente , Zolpidem
15.
Rev. gaúch. enferm ; Rev. gaúch. enferm;41: e20190068, 2020. tab
Artículo en Inglés | LILACS, BDENF - Enfermería | ID: biblio-1139159

RESUMEN

ABSTRACT Objective: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Method: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. Results: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. Conclusion: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.


RESUMEN Objetivo: Establecer la prevalencia del delirio y su subsíndrome en pacientes de cuidados intensivos y asociarlos con el uso de la sedoanalgesia, con la gravedad y con la mortalidad. Método: Realizado en dos unidades de cuidados intensivos de pacientes adultos, se trata de un estudio cuantitativo y transversal, con 157 pacientes, utilizando las escalas Richmond Agitation-Sedation Scale (Escala de agitación-sedación de Richmond) para evaluar el nivel de sedación y la de la Intensive Care Delirium Screening Checklist (Lista de verificación para la detección del delirio en cuidados intensivos) para el delirio. Se aplicaron las pruebas de T y Chi-cuadrado para el análisis estadístico. Resultados: La prevalencia del delirio fue del 22,3%, y la del subsíndrome fue del 49,7%. Se han encontrado asociaciones del uso de midazolan con la presencia de delirio (p = 0,05) y del deilirio subsindromático (p < 0,01), del uso de clonidina con la aparición de delirio (p < 0,01) y de fentanil con el delirio subsindromático (p = 0,09). No se registraron diferencias significativas entre la mortalidad de los pacientes con delirio (p = 0,40) y el delirio. Conclusión: El uso de sedoanalgesia se asocia con la presencia de delirio y delirio subsindromático. No se encontraron asociaciones estadísticas significativas entre la gravedad y las puntuaciones de mortalidad.


RESUMO Objetivo: Estabelecer a prevalência do delirium e sua subsíndrome em pacientes de terapia intensiva e associar com uso de sedoanalgesia, gravidade e mortalidade. Método: Realizado em duas Unidades de Terapia Intensiva de pacientes adultos, trata-se de estudo quantitativo e transversal, com 157 pacientes, utilizando as escalas Richmond Agitation-Sedation Scale para avaliação do nível de sedação e Intensive Care Delirium Screening Checklist para delirium. Foi aplicado o teste t e qui-quadrado para análise estatística. Resultados: A prevalência de delirium foi 22,3% e da subsíndrome 49,7%. Foram encontradas associações do uso de midazolan com a presença de delirium (p=0,05) e delirium subsindromático (p<0,01), uso de clonidina com o aparecimento de delirium (p<0,01) e de fentanil com o delirium subsindromático (p=0,09). Não houve diferenças significativas entre mortalidade de paciente com delirium (p=0,40) e delirium subsindromático (p= 0,86), bem como associação com o escore de mortalidade. Conclusão: O uso de sedoanalgesia está associado à presenta de delirium e delirium subsindromático. Não foram encontradas associações estatísticas significativas entre os escores de gravidade e mortalidade.


Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Críticos/estadística & datos numéricos , Delirio/epidemiología , Analgésicos/efectos adversos , Hipnóticos y Sedantes/efectos adversos , Midazolam/administración & dosificación , Midazolam/efectos adversos , Midazolam/uso terapéutico , Distribución de Chi-Cuadrado , Propofol/administración & dosificación , Propofol/efectos adversos , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Prevalencia , Estudios Transversales , Clonidina/administración & dosificación , Clonidina/efectos adversos , Delirio/inducido químicamente , Analgésicos/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Unidades de Cuidados Intensivos
16.
Rev. gaúch. enferm ; Rev. gaúch. enferm;41: e20190068, 2020. tab
Artículo en Inglés | LILACS, BDENF - Enfermería | ID: biblio-1101683

RESUMEN

ABSTRACT Objective: To establish the prevalence of delirium and its subsyndrome in intensive care and to associate it with the use of sedative and analgesia, severity and mortality. Method: Carried out in two intensive care units of adult patients, this is a quantitative and transversal study, with 157 patients, using the Richmond Agitation-Sedation Scale to assess the level of sedation and the Intensive Care Delirium Screening Checklist for delirium. The T test and Chi-square test were applied for statistical analysis. Results: The prevalence of delirium was 22.3%, and 49.7% of the subsyndrome. Associations of the use of midazolam with the presence of delirium (p=0.05) and subsyndromal delirium (p<0.01), use of clonidine with the appearance of delirium (p<0.01) and of fentanyl with subsyndromal delirium (p=0.09). There were no significant differences between the mortality of patients with delirium (p=0.40) and subsyndromal delirium (p=0.86), as well as association with the mortality score. Conclusion: The use of sedoanalgesia is associated with the presence of delirium and subsyndromal delirium. No significant statistical associations were found between the severity and mortality scores.


RESUMEN Objetivo: Establecer la prevalencia del delirio y su subsíndrome en pacientes de cuidados intensivos y asociarlos con el uso de la sedoanalgesia, con la gravedad y con la mortalidad. Método: Realizado en dos unidades de cuidados intensivos de pacientes adultos, se trata de un estudio cuantitativo y transversal, con 157 pacientes, utilizando las escalas Richmond Agitation-Sedation Scale (Escala de agitación-sedación de Richmond) para evaluar el nivel de sedación y la de la Intensive Care Delirium Screening Checklist (Lista de verificación para la detección del delirio en cuidados intensivos) para el delirio. Se aplicaron las pruebas de T y Chi-cuadrado para el análisis estadístico. Resultados: La prevalencia del delirio fue del 22,3%, y la del subsíndrome fue del 49,7%. Se han encontrado asociaciones del uso de midazolan con la presencia de delirio (p = 0,05) y del deilirio subsindromático (p < 0,01), del uso de clonidina con la aparición de delirio (p < 0,01) y de fentanil con el delirio subsindromático (p = 0,09). No se registraron diferencias significativas entre la mortalidad de los pacientes con delirio (p = 0,40) y el delirio. Conclusión: El uso de sedoanalgesia se asocia con la presencia de delirio y delirio subsindromático. No se encontraron asociaciones estadísticas significativas entre la gravedad y las puntuaciones de mortalidad.


RESUMO Objetivo: Estabelecer a prevalência do delirium e sua subsíndrome em pacientes de terapia intensiva e associar com uso de sedoanalgesia, gravidade e mortalidade. Método: Realizado em duas Unidades de Terapia Intensiva de pacientes adultos, trata-se de estudo quantitativo e transversal, com 157 pacientes, utilizando as escalas Richmond Agitation-Sedation Scale para avaliação do nível de sedação e Intensive Care Delirium Screening Checklist para delirium. Foi aplicado o teste t e qui-quadrado para análise estatística. Resultados: A prevalência de delirium foi 22,3% e da subsíndrome 49,7%. Foram encontradas associações do uso de midazolan com a presença de delirium (p=0,05) e delirium subsindromático (p<0,01), uso de clonidina com o aparecimento de delirium (p<0,01) e de fentanil com o delirium subsindromático (p=0,09). Não houve diferenças significativas entre mortalidade de paciente com delirium (p=0,40) e delirium subsindromático (p= 0,86), bem como associação com o escore de mortalidade. Conclusão: O uso de sedoanalgesia está associado à presenta de delirium e delirium subsindromático. Não foram encontradas associações estatísticas significativas entre os escores de gravidade e mortalidade.


Asunto(s)
Femenino , Humanos , Masculino , Persona de Mediana Edad , Cuidados Críticos/estadística & datos numéricos , Delirio/epidemiología , Analgésicos/efectos adversos , Hipnóticos y Sedantes/efectos adversos , Midazolam/administración & dosificación , Midazolam/efectos adversos , Midazolam/uso terapéutico , Distribución de Chi-Cuadrado , Propofol/administración & dosificación , Propofol/efectos adversos , Fentanilo/administración & dosificación , Fentanilo/efectos adversos , Prevalencia , Estudios Transversales , Clonidina/administración & dosificación , Clonidina/efectos adversos , Delirio/inducido químicamente , Analgésicos/administración & dosificación , Hipnóticos y Sedantes/administración & dosificación , Unidades de Cuidados Intensivos
17.
Rev. chil. anest ; 49(6): 874-881, 2020. tab, graf
Artículo en Español | LILACS | ID: biblio-1512274

RESUMEN

INTRODUCTION: Tonsillectomy with or without adenoidectomy is one of the most frequent surgeries in the pediatric population. It has become predomi- nantly an outpatient procedure. Therefore, it is of utmost importance identi- fying the factors that influence the intraoperative bleeding to prevent posto- perative complications and rehospitalization. MATERIAL AND METHODS: An observational cross-sectional study was carried out. Patients between 1 and 14 years old that underwent to tonsillectomy with or without adenoidectomy since November 2015 to May 2017 were included. 709 cases were evaluated. Intraoperative bleeding was assessed by the volumetric method. A multivariate analysis was performed using a generalized linear regression model. RESULTS: The average intraoperative bleeding was estimated in 1.9 ml/kg (95% CI: 1.7 -2.05). The use of propofol (30% increase in bleeding) and surgical time (2% increase for every minute) were risk factors. The use of electrocautery was as- sociated with a 50% decrease in bleeding in comparison with conventional dis- section (p = 0.001). CONCLUSION: The use of propofol and a prolonged surgical time were risk factors for intraoperative bleeding. The use of electrosurgery was a protective factor.


INTRODUCCIÓN: La amigdalectomía con o sin adenoidectomía, es una de las cirugías más frecuente en población pediátrica. Desde hace varios años se ha vuelto una intervención predominantemente ambulatoria, por lo que lograr identificar los factores que influyen en el sangrado intraoperatorio es de suma importancia para prevenir complicaciones postoperatorias y reshospitalización. MATERIAL Y MÉTODO: Se realizó un estudio observacional de corte-transversal. Se incluyó a pacientes entre 1 y 14 años sometidos a amigdalectomía con o sin adenoidectomía entre noviembre de 2015 y mayo de 2017, obteniendo un total de 709 casos evaluados. Se determinó el sangrado intraoperatorio de forma volumétrica. Posteriormente, se realizó un análisis multivariado con un modelo de regresión lineal generalizado. RESULTADOS: Se cuantificó el sangrado intraoperatorio promedio en 1,9 ml/kg (IC 95%; 1,7-2,05). El uso de propofol (aumento del 30% del sangrado) y tiempo quirúrgico (2% por cada incremento de un minuto) fueron factores de riesgo. Mientras que el uso de electro bisturí se asoció con una disminución del 50% en relación al no uso (p = 0,001). CONCLUSIONES: Fueron factores de riesgo para sangrado intraoperatorio el uso de propofol y un tiempo quirúrgico prolongado. El uso de electrobisturí constituyó un factor protector.


Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Tonsilectomía/efectos adversos , Propofol/efectos adversos , Pérdida de Sangre Quirúrgica , Modelos Logísticos , Estudios Transversales , Análisis Multivariante , Factores de Riesgo , Anestésicos Intravenosos/efectos adversos , Complicaciones Intraoperatorias
18.
Rev Chil Pediatr ; 89(3): 384-390, 2018 Jun.
Artículo en Español | MEDLINE | ID: mdl-29999146

RESUMEN

INTRODUCTION: Propofol Infusion Syndrome (PRIS) is a rare but potentially lethal adverse reaction secondary to the continuous intravenous infusion of this drug. The diagnosis is based on the com bination of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperli pidemia, arrhythmias, and rapidly progressive heart failure. OBJECTIVE: To report a case of PRIS and literature review. CLINICAL CASE: A 6-year-old female patient with history of epilepsy secondary to large malformation of cortical development of the right hemisphere. The patient presented a refractory status epilepticus that required admission to the Intensive Care Unit for life support and treatment, which included continuous intravenous infusion of propofol at 10 mg/kg/h. She developed hemo dynamic instability, and after 24 h of treatment an increase of creatine phosphokinase (CPK) levels, metabolic acidosis and elevated lactacidemia were observed. After ruling out other causes, PRIS was diagnosed; therefore, the drug was suspended, achieving hemodynamic stabilization after 24 hours. DISCUSSION: The diagnosis of PRIS is complex and should be considered in patients who are receiving this drug and present metabolic acidosis or heart failure. The factors that most influence mortality are the cumulative dose of the drug, the presence of fever, and cranial brain injury. In the case described, the patient received a dose higher than 4 mg/kg/h, which is the maximum recommended dose, and responded favorably 12 hours after stopping the drug.


Asunto(s)
Anticonvulsivantes/efectos adversos , Síndrome de Infusión de Propofol/diagnóstico , Propofol/efectos adversos , Estado Epiléptico/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Niño , Femenino , Humanos , Inyecciones Intravenosas , Propofol/uso terapéutico , Síndrome de Infusión de Propofol/etiología , Estado Epiléptico/complicaciones
19.
Rev. chil. pediatr ; 89(3): 384-390, jun. 2018. tab
Artículo en Español | LILACS | ID: biblio-959538

RESUMEN

INTRODUCCIÓN: El síndrome por infusión de propofol (SIP) es una reacción adversa poco frecuente, pero potencialmente letal descrita por la utilización de dicho fármaco en infusión intravenosa (IV) continua. El diagnóstico se basa en la combinación de acidosis metabólica, rabdomiolisis, hiperkalemia, hepatomegalia, insuficiencia renal, hiperlipidemia, arritmias e insuficiencia cardiaca rápida mente progresiva. OBJETIVO: Presentación de un caso clínico de SIP y revisión de literatura. CASO CLÍNICO: Paciente femenino de 6 años de edad con antecedentes de epilepsia secundaria a extensa alteración del desarrollo cortical hemisférico derecho. Presentó estatus epiléptico refractario que requirió ingreso a Unidad de Cuidados Intensivos para soporte vital y tratamiento, el que incluyó como terapia de tercera línea infusión intravenosa continua de propofol en dosis progresivas hasta alcanzar una tasa 10 mg/kg/h. Cursó con compromiso hemodinámico y a las 24 h de iniciado el tratamiento se observó alza de la creatinifosfokinasa (CK), acidosis metabólica y lactacidemia elevada, y luego de descartar otras causas se planteó el diagnóstico de SIP por lo que se suspendió la droga, logrando estabilización hemodinámica a las 24 h. DISCUSIÓN: El diagnóstico de SIP es complejo, se debe considerar en pacientes que estén recibiendo el fármaco y presenten acidosis metabólica o insuficiencia cardiaca. Los factores que más influyen en la mortalidad son la dosis acumulativa de la droga, la presencia de fiebre y lesión encéfalo craneana. En el caso descrito la paciente recibió una dosis mayor a 4 mg/ kg/h que es la dosis máxima recomendada y respondió favorablemente luego de 12 h después de la suspensión del fármaco.


INTRODUCTION: Propofol Infusion Syndrome (PRIS) is a rare but potentially lethal adverse reaction secondary to the continuous intravenous infusion of this drug. The diagnosis is based on the com bination of metabolic acidosis, rhabdomyolysis, hyperkalemia, hepatomegaly, renal failure, hyperli pidemia, arrhythmias, and rapidly progressive heart failure. OBJECTIVE: To report a case of PRIS and literature review. CLINICAL CASE: A 6-year-old female patient with history of epilepsy secondary to large malformation of cortical development of the right hemisphere. The patient presented a refractory status epilepticus that required admission to the Intensive Care Unit for life support and treatment, which included continuous intravenous infusion of propofol at 10 mg/kg/h. She developed hemo dynamic instability, and after 24 h of treatment an increase of creatine phosphokinase (CPK) levels, metabolic acidosis and elevated lactacidemia were observed. After ruling out other causes, PRIS was diagnosed; therefore, the drug was suspended, achieving hemodynamic stabilization after 24 hours. DISCUSSION: The diagnosis of PRIS is complex and should be considered in patients who are receiving this drug and present metabolic acidosis or heart failure. The factors that most influence mortality are the cumulative dose of the drug, the presence of fever, and cranial brain injury. In the case described, the patient received a dose higher than 4 mg/kg/h, which is the maximum recommended dose, and responded favorably 12 hours after stopping the drug.


Asunto(s)
Humanos , Femenino , Niño , Estado Epiléptico/tratamiento farmacológico , Propofol/efectos adversos , Síndrome de Infusión de Propofol/diagnóstico , Anticonvulsivantes/efectos adversos , Estado Epiléptico/complicaciones , Propofol/uso terapéutico , Síndrome de Infusión de Propofol/etiología , Inyecciones Intravenosas , Anticonvulsivantes/uso terapéutico
20.
Mutagenesis ; 33(2): 147-152, 2018 04 13.
Artículo en Inglés | MEDLINE | ID: mdl-29669111

RESUMEN

Despite the widespread use of the anaesthetics propofol (PROP) and isoflurane (ISO), data about their toxicogenomic potential and interference in epigenetic events are unknown. This study evaluated the expression and methylation profile of two important DNA-repair genes (XRCC1 and hOGG1) in 40 patients undergoing elective and minimally invasive surgery (tympanoplasty and septoplasty) under ISO or PROP anaesthesia. The endpoints were examined at three sampling times: before anaesthesia (T0), 2 h after the beginning of anaesthesia (T2) and 24 h after the beginning of surgery (T24). Both gene expressions were assessed by quantitative real-time polymerase chain reaction (qRT-PCR), whereas methylation specific-PCR (MS-PCR) evaluated the DNA methylation patterns. Increased expression of XRCC1 was observed at T2 only in the PROP group. On the other hand, hOGG1 and XRCC1 expressions were decreased at T24 in both groups. There were no statistical significant differences between the two anaesthetics at the respective sampling times. The methylation status of XRCC1 (methylated at T0) and hOGG1 (unmethylated at T0) remained unchanged in the three sampling times. In conclusion, this study showed modulations of hOGG1 and XRCC1 expression especially 1 day after elective surgery in patients undergoing PROP and ISO anaesthesia. However, the data indicated that methylation was not the mechanism by which the genes were regulated. More studies are warranted to further investigate the possible epigenetic mechanisms involved after exposure to anaesthetics.


Asunto(s)
ADN Glicosilasas/genética , Isoflurano/efectos adversos , Propofol/efectos adversos , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Adulto , Anestesia/efectos adversos , Metilación de ADN/efectos de los fármacos , Metilación de ADN/genética , Reparación del ADN/efectos de los fármacos , Reparación del ADN/genética , Femenino , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Isoflurano/administración & dosificación , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Regiones Promotoras Genéticas/efectos de los fármacos , Propofol/administración & dosificación
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