Anesthesia and analgesia最新文献

Background: Ketamine administration during stable propofol anesthesia is known to be associated with an increase in bispectral index (BIS) but a "deepening" in the level of hypnosis. This study aimed to evaluate the association between the effect-site concentration of ketamine (CeK) and 2 electroencephalogram (EEG)-derived parameters, the BIS and spectral edge frequency (SEF95), after the administration of a ketamine bolus. Secondary aims included investigating the BIS and SEF95 variations with time and changes in the surgical pleth index (SPI).

Methods: We conducted an observational, prospective, single-center study analyzing intraoperative data from 14 adult female patients undergoing breast oncologic surgery. During stable propofol-remifentanil target-controlled infusion (TCI) anesthesia, a ketamine analgesic bolus was delivered with the target CeK set to 1 μg.mL-1 (Domino model) corresponding to a dose of 0.57 mg.kg-1 (interquartile range [IQR] 0.56-0.57 mg.kg-1). Once the CeK reached a value of 1 μg.mL-1, the target CeK was set to 0 μg.mL-1. We determined the median BIS, SEF95, and SPI trends with time and as a function of the modeled CeK.

Results: BIS and SEF95 showed no significant change from when ketamine was administered to when CeK=1 μg.mL-1, but a significant increase was observed at lower CeKs. The maximum BIS was reached at 16.0 minutes [10.2-22.7 minutes] after CeK=1 μg.mL-1, at CeK=0.22 μg.mL-1 [0.12-0.41 μg.mL-1]. The peak SEF95 value was observed at 10.0 minutes [8.62-14.1 minutes] after CeK=1 μg.mL-1, at CeK=0.43 μg.mL-1 [0.25-0.50 μg.mL-1]. No significant association was found between CeK and the registered SPI values.

Conclusions: Our results show that BIS and SEF95, but not SPI, follow a CeK-dependent trend after administering a ketamine bolus. Interestingly, their peak values were not reached at CeK=1 μg.mL-1, but after several minutes after the drug infusion at CeKs in the 0.2 to 0.5 μg.mL-1 range. This may be explained by the specific pharmacodynamics of ketamine and its varying effects at different concentrations, as well as by the time delay associated with the calculation of the BIS.

Traditional pediatric anesthetic dosing using pharmacokinetic estimates based on age and weight is often imprecise, frequently leading to oversedation. Intraoperative electroencephalography (EEG) allows visualization of the brain's response to anesthetic agents in real time, facilitating precise titration of anesthetic drug doses optimized for the individual child. The goal of EEG-guided anesthesia management is to maintain an optimal state of hypnosis during various stages of the procedure while minimizing hemodynamic instability and other adverse effects of anesthesia. This is especially important in children with less predictable anesthetic requirements, such as children with atypical neurodevelopment, altered levels of consciousness before anesthesia, or those receiving total intravenous anesthesia, neuromuscular blockers, or a combination of anesthetic agents with different mechanisms of actions. Children with limited cardiorespiratory reserves and those undergoing high-risk procedures such as cardiopulmonary bypass also benefit from EEG guidance as they have a narrower therapeutic window for optimal anesthetic dosing. Various processed EEG (pEEG) monitors are available for intraoperative monitoring in children. These monitors display a pEEG index based on the manufacturer's algorithm, purportedly indicating the patient's hypnotic state. Due to differences in developmental neurophysiology and EEG dynamics in children, pEEG indices may not always reliably indicate the hypnotic state, especially in neonates and infants. Learning to interpret nonproprietary EEG parameters including the raw EEG, spectral-edge frequency 95% (SEF95), and density spectral array can prevent overreliance on pEEG indices. This review provides an overview of the advantages of EEG guidance during clinical anesthesia, including potential reduction in anesthetic dosage, prevention of EEG suppression, and reduction in peri-operative adverse events. We describe the use of nonproprietary EEG parameters in guiding anesthesia in children for various clinical end points including laryngoscopy, surgical incision, and maintenance of anesthesia, as well as sedation. We illustrate these principles with various case examples commonly encountered during pediatric anesthesia. Lastly, we discuss strategies to expand intraoperative EEG monitoring in children through education and training programs, as well as advocate for further research to assess clinical outcomes associated with EEG guidance to support its routine use in clinical care.

Background: Chronic pain is a debilitating medical condition that lacks effective treatments. Increasing evidence suggests that microglia and neuroinflammation underlie pain pathophysiology, which therefore supports a potential strategy for developing pain therapeutics. Here, our study is testing the hypothesis that the promise of pain amelioration can be achieved using the small-molecule pexidartinib (PLX-3397), a previously food and drug administration (FDA)-approved cancer medicine and a colony-stimulating factor-1 receptor (CSF-1R) inhibitor that display microglia-depleting properties.

Method: We used the previously reported chronic constriction injury (CCI) mouse model, in which PLX-3397 or vehicle was orally administrated to mice daily for 21 days, then applied to the CCI model, followed by PLX-3397 or vehicle administration for an additional 28 days. Additionally, we examined microglia-related neuroinflammation markers using positron emission tomography (PET) neuroimaging and immunofluorescence (IF).

Results: We showed that PLX-3397 significantly ameliorated pain-related behavioral changes throughout the entire experimental period after CCI (vehicle versus PLX-3397 at day 14, effect size: 2.57, P = .002). Microglia changes were first analyzed by live-animal PET neuroimaging, revealing PLX-3397-associated reduction of microglia by probing receptor-interacting serine/threonine-protein kinase 1 (RIPK1), a protein primarily expressed in microglia, which were further corroborated by postmortem immunohistochemistry (IHC) analysis using antibodies for microglia, including ionized Ca2+ binding adaptor molecule 1 (Iba-1) (somatosensory cortex, hindlimb area; vehicle versus PLX-3397, effect size 3.6, P = .011) and RIPK1 (somatosensory cortex, hindlimb area; vehicle versus PLX-3397, effect size 2.9, P = .023. The expression of both markers decreased in the PLX-3397 group. Furthermore, we found that PLX-3397 led to significant reductions in various proteins, including inducible nitric oxide synthase (iNOS) (somatosensory cortex, hindlimb area; vehicle versus PLX-3397, effect size: 2.3, P = .048), involved in neuroinflammation through IHC.

Conclusions: Collectively, our study showed PLX-3397-related efficacy in ameliorating pain linked to the reduction of microglia and neuroinflammation in mice. Furthermore, our research provided new proof-of-concept data supporting the promise of testing PLX-3397 as an analgesic.

Background: Critical incidents and mortality related to anesthesia are more frequently observed in low- and middle-income countries in comparison to high-income countries. The difficulties linked to anesthesia in rural areas of the Democratic Republic of the Congo (DRC) and Tanzania have limited documentation. The aim of this study was to comprehensively document anesthesia-related critical events that occurred during surgical missions organized by the nongovernmental organization 2nd Chance in hospitals in DRC and Tanzania.

Methods: Data were collected during 6 surgical missions in 3 hospitals in the DRC and 1 in Tanzania. All scheduled surgery patients were included. Anesthesia was administered by a local Non-Physician Anesthesia Provider (NPAP), using local resources, under the supervision of an anesthesiologist from the association. The anesthesiologist reported critical events and collected data. Local teams managed critical events initially, with intervention by the anesthesiologist from 2nd Chance on the local team's request, according to preestablished protocol or if the situation was considered dangerous. Critical incidents associated with anesthesia, including bradycardia, hypoxemia, airway management failure, and equipment problems, were documented from induction of anesthesia until discharge from the recovery room.

Results: We recruited 201 patients, of whom 192 were evaluated, with 9 patients dropping out due to protocol noncompliance. All patients were American Society of Anesthesiologists (ASA) I (62%; n = 120) or ASA II (38%; n = 72). Among them, 104 individuals (54%) experienced at least 1 critical event, totaling 202 critical events. Hypoxemia emerged as the most common event, affecting 29% of the patients (n = 55) with at least 1 episode. Equipment problems (oxygen supply and/or anesthesia machine failure) occurred in 24% of cases (n = 46), airway management issues in 23% (n = 44), and bradycardia in 6% (n = 12). Hypotension and hypertension were not documented due to the lack of monitoring. The majority of these events (over 60%) required intervention by the anesthesiologist.

Conclusions: The occurrence of critical events related to anesthesia appears to be high in this study. Due to numerous limitations, these results cannot be generalized to all hospitals in Tanzania and the DRC. However, this study underscores the challenges faced by anesthesia teams, encompassing inadequate resources, equipment deficiencies, and varying levels of expertise among anesthesia personnel. The research further stresses the significance of addressing these challenges to enhance patient safety.