Comparative evaluation of intranasal dexmedetomidine, intranasal midazolam, and nitrous oxide for conscious sedation of anxious children undergoing dental treatment: A randomized cross-over trial.

BACKGROUND: Pharmacological methods, specifically sedatives, have gained popularity in managing the behavior of children during dental appointments. AIM: The aim of this study was to compare 1 m/kg intranasal dexmedetomidine, 0.3 mg/kg intranasal midazolam, and nitrous oxide in evaluating the level of sedation, behavior of the child, onset of sedation, physiologic signs, and adverse effects. MATERIALS AND METHODS: In this cross-over trial, 15 children aged 6-8 years were randomized to receive intranasal atomized dexmedetomidine, intranasal atomized midazolam, and inhalation nitrous oxide at three separate visits. After administering the sedative agent, a single pulpectomy was performed during each appointment, and the outcomes were recorded. The washout period between each visit was 1 week. RESULTS: All three sedative agents were equally effective in controlling overall behavior. Dexmedetomidine showed lower sedation level scores (agitated; score 9) than the other groups. There was a statistically significant difference in the onset of sedation, with dexmedetomidine having the longest onset of 36.2 ± 9.47 min. Coughing and sneezing were predominantly observed after administration of intranasal midazolam. Oxygen saturation levels were statistically lower in the intranasal midazolam group during local anesthesia administration and post-treatment. CONCLUSION: 0.3 mg/kg intranasal midazolam is as effective as nitrous oxide sedation for controlling behavior and providing adequate sedation in pediatric dental patients. However, 1 m/kg dexmedetomidine did not provide the same level of sedation and had a significantly longer onset. 0.3 mg/kg intranasal midazolam is an effective alternative to nitrous oxide sedation in anxious children.

Zona incerta mediates early life isoflurane-induced fear memory deficits.

The potential long-term effects of anesthesia on cognitive development, especially in neonates and infants, have raised concerns. However, our understanding of its underlying mechanisms and effective treatments is still limited. In this study, we found that early exposure to isoflurane (ISO) impaired fear memory retrieval, which was reversed by dexmedetomidine (DEX) pre-treatment. Measurement of c-fos expression revealed that ISO exposure significantly increased neuronal activation in the zona incerta (ZI). Fiber photometry recording showed that ZI neurons from ISO mice displayed enhanced calcium activity during retrieval of fear memory compared to the control group, while DEX treatment reduced this enhanced calcium activity. Chemogenetic inhibition of ZI neurons effectively rescued the impairments caused by ISO exposure. These findings suggest that the ZI may play a pivotal role in mediating the cognitive effects of anesthetics, offering a potential therapeutic target for preventing anesthesia-related cognitive impairments.

Comparison of the effects of axillary brachial plexus block, inhalation anesthesia, and total intravenous anesthesia on tourniquet-induced ischemia-reperfusion injury in upper extremity surgery.

BACKGROUND: Post-ischemia reperfusion can lead to oxidative stress and an increase in oxidative markers. Employing preventive strategies and antioxidant agents may help mitigate ischemia-reperfusion injury (IRI). The use of a tourniquet in extremity surgery has been associated with IRI. This study aims to investigate the impact of three different approaches- brachial plexus block, total intravenous anesthesia (TIVA), and inhalation anesthesia-on IRI during upper extremity surgery using a tourniquet. METHODS: Patients aged 18 to 45 with American Society of Anesthesiologists (ASA) I-II scores were randomly assigned to one of three groups: Group A received an axillary block with bupivacaine; Group I underwent inhalation anesthesia with sevoflurane; and Group T received TIVA with propofol and remifentanil infusion. Blood samples were collected to measure glucose, lactate, total anti-oxidant status (TAS), total oxidant status (TOS), and ischemia-modified albumin (IMA) levels at various time points: before anesthesia (t1), 1 minute before tourniquet release (t2), 20 minutes after tourniquet release (t3), and 4 hours after tourniquet release (t4). RESULTS: In Group I, lactate levels at t3, and glucose levels at t2 and t3, were higher compared to the other groups. Group A exhibited lower IMA levels at t2, t3, and t4 than the other groups. Additionally, Group I had lower IMA levels at t2, t3, and t4 compared to Group T. TAS levels were higher in Group I at t2, t3, and t4 compared to the other groups. TOS levels at t2 and t3 were lower in Group A than in Group I. CONCLUSION: Axillary anesthesia results in a sympathetic block, promoting better perfusion of the upper extremity. This study demonstrated lower levels of oxidative stress markers with axillary plexus block. Therefore, these results suggest that the axillary block has the potential to mitigate IRI.

Short-term inhalation of xenon during anesthesia for prevention of postoperative delirium in elderly patients undergoing laparoscopic radical colectomy: study protocol for a randomized controlled clinical trial.

BACKGROUND: Postoperative delirium (POD) is a common complication that is characterized by acute onset of impaired cognitive function and is associated with an increased mortality, a prolonged duration of hospital stay, and additional healthcare expenditures. The incidence of POD in elderly patients undergoing laparoscopic radical colectomy ranges from 8 to 54%. Xenon has been shown to provide neuroprotection in various neural injury models, but the clinical researches assessing the preventive effect of xenon inhalation on the occurrence of POD obtained controversial findings. This study aims to investigate the effects of a short xenon inhalation on the occurrence of POD in elderly patients undergoing laparoscopic radical colectomy. METHODS/DESIGN: This is a prospective, randomized, controlled trial and 132 patients aged 65-80 years and scheduled for laparoscopic radical colectomy will be enrolled. The participants will be randomly assigned to either the control group or the xenon group (n = 66 in each group). The primary outcome will be the incidence of POD in the first 5 days after surgery. Secondary outcomes will include the subtype, severity, and duration of POD, postoperative pain score, Pittsburgh Sleep Quality Index (PQSI), perioperative non-delirium complications, and economic parameters. Additionally, the study will investigate the activation of microglial cells, expression of inflammatory factors in colon tissues, plasma inflammatory factors, and neurochemical markers. DISCUSSION: Elderly patients undergoing laparoscopic radical colectomy are at a high risk of POD, with delayed postoperative recovery and increased healthcare costs. The primary objective of this study is to determine the preventive effect of a short xenon inhalation on the occurrence of POD in these patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300076666. Registered on October 16, 2023, http://www.chictr.org.cn .

Effects of different anesthetic regimens on postoperative cognitive function of elderly patients undergoing thoracic surgery: a double-blinded randomized controlled trial.

OBJECTIVE: Postoperative cognitive dysfunction (POCD) is a serious surgical complication. We assessed the different POCD incidences between anesthesia using sevoflurane and sevoflurane combined with dexmedetomidine, with propofol-based sedation in elderly patients who underwent a thoracic surgical procedure. METHODS: A total of 90 patients aged 65 to 80 years old who underwent a thoracic surgical procedure at our hospital and 15 nonsurgical participants as controls, were enrolled in this study. Patients were divided in a randomized 1:1:1 ratio into 3 groups. All participants were randomized into a trial with three anesthesia groups (P, PS, PSD) or a control group (C) of healthy matches. All trial groups received distinct anesthetic combinations during surgery, while controls mirrored patient criteria.Group P (propofol and remifentanil were maintained during the surgery), Group PS (propofol, remifentanil, and sevoflurane were maintained during the surgery), and Group PSD (propofol, remifentanil, sevoflurane, and dexmedetomidine were maintained during the surgery).All participants were rated using a series of cognitive assessment scales before and three days after surgery. All participants were interviewed over the telephone, 7 days, 30 days, and 90 days postoperatively. RESULTS: POCD incidences in the PSD (combined anesthetization with propofol, sevoflurane, and dexmedetomidine) group was significantly lower than that in the PS (combined anesthetization with propofol and sevoflurane) group, 1 day post-surgery (10.0% vs. 40.0%, P = 0.008), and the results were consistent at 3 days post-surgery. When the patients were assessed 7 days, 30 days, and 90 days postoperatively, there was no significant difference in POCD incidence among the three groups. Multivariate logistic regression analysis of POCD one day after surgery showed that education level was negatively correlated with incidence of POCD (P = 0.018) and single lung ventilation time was positively correlated with incidence of POCD (P = 0.001). CONCLUSION: For elderly patients who underwent a thoracic surgical procedure, dexmedetomidine sedation shows an obvious advantage on improving short-term POCD incidence, which is caused by sevoflurane.

The Impact of the Combined Effect of Inhalation Anesthetics and Iron Dextran on Rats' Systemic Toxicity.

Disruption of any stage of iron homeostasis, including uptake, utilization, efflux, and storage, can cause progressive damage to peripheral organs. The health hazards associated with occupational exposure to inhalation anesthetics (IA) in combination with chronic iron overload are not well documented. This study aimed to investigate changes in the concentration of essential metals in the peripheral organs of rats after iron overload in combination with IA. The aim was also to determine how iron overload in combination with IA affects tissue metal homeostasis, hepcidin-ferritin levels, and MMP levels according to physiological, functional, and tissue features. According to the obtained results, iron accumulation was most pronounced in the liver (19×), spleen (6.7×), lungs (3.1×), and kidneys (2.5×) compared to control. Iron accumulation is associated with elevated heavy metal levels and impaired essential metal concentrations due to oxidative stress (OS). Notably, the use of IA increases the iron overload toxicity, especially after Isoflurane exposure. The results show that the regulation of iron homeostasis is based on the interaction of hepcidin, ferritin, and other proteins regulated by inflammation, OS, free iron levels, erythropoiesis, and hypoxia. Long-term exposure to IA and iron leads to the development of numerous adaptation mechanisms in response to toxicity, OS, and inflammation. These adaptive mechanisms of iron regulation lead to the inhibition of MMP activity and reduction of oxidative stress, protecting the organism from possible damage.

Environmental impact of anesthetic drugs.

PURPOSE OF REVIEW: The environmental impact of anesthesia far exceeds that of other medical specialties due to our use of inhaled anesthetic agents (which are potent greenhouse gases) and many intravenous medications. RECENT FINDINGS: Calls for reducing the carbon footprint of anesthesia are ubiquitous in the anesthesia societies of developed nations and are appearing in proposed changes for hospital accreditation and funding in the United States. The body of research on atmospheric, land and water impacts of anesthetic pharmaceuticals is growing and generally reinforces existing recommendations to reduce the greenhouse gas emissions of anesthesia care. SUMMARY: The environmental impact of anesthesia care should factor into our clinical decisions. The onus is on clinicians to safely care for our patients in ways that contribute the least harm to the environment. Intravenous anesthesia and regional techniques have less environmental impact than the use of inhaled agents; efforts to reduce and properly dispose of pharmaceutical waste are central to reducing environmental burden; desflurane should not be used; nitrous oxide should be avoided except where clinically necessary; central nitrous pipelines should be abandoned; low fresh gas flows should be utilized whenever inhaled agents are used.

[Nitrous oxide as a party drug]. / Partydroge Lachgas.

In recent years, reports of health problems associated with nitrous oxide consumption have significantly increased. In Germany, nitrous oxide (N2O) is easily available in cartridges without legal restrictions. The main reason for its popularity in the party scene are the euphoric, psychedelic effects of the gas. In addition to severe and sometimes irreversible health problems associated with long-term use of nitrous oxide, e.g., anemia and nerve damage, life-threatening or fatal consequences of acute nitrous oxide consumption can also occur: accidents under the influence of nitrous oxide, pneumothorax, pneumopericardium and shock due to an explosive increase in airway pressure when inhaled directly from the cartridge. But the most common cause of severe complications is asphyxia as the gas is usually inhaled pure from large balloons and without oxygen. The resulting hypoxia during use may be perpetuated by the diffusion hypoxia that occurs during the reoxygenation period. Nitrous oxide as a cause in accidental or intoxication events is usually not detectable but can only be identified as a trigger based on the patient's history or the circumstances. Acute medical treatment is symptomatic.

EVALUATION OF IMMERSION IN EMULSIFIED ISOFLURANE OR PROPOFOL AS PART OF A TWO-STEP EUTHANASIA PROTOCOL IN MARBLED CRAYFISH (PROCAMBARUS VIRGINALIS).

The marbled crayfish (Procambarus virginalis) is a parthenogenetic invasive species across much of the world, and when found, euthanasia is often recommended to reduce spread to naïve ecosystems. Euthanasia recommendations in crustaceans includes a two-step method: first to produce nonresponsiveness and then to destroy central nervous tissue. Minimal data exist on adequate anesthetic or immobilization methods for crayfish. A population of 90 marbled crayfish was scheduled for euthanasia due to invasive species concerns. The population was divided into six treatment groups to evaluate whether immersion in emulsified isoflurane or propofol solutions could produce nonresponsiveness. Each group was exposed to one of six treatments for 1 h: isoflurane emulsified at 0.1%, 0.5%, 2%, 5%, and 15% or propofol at 10 mg/L and then increased to 100 mg/L. Crayfish from all treatment groups were moved to nonmedicated water after completion of 1 h and observed for an additional 4 h. All crayfish treated with isoflurane showed lack of a righting reflex at 5 min and loss of movement after 30 min. By 240 min (4 h), none of the crayfish from the isoflurane treatment groups regained movement. None of the crayfish in the propofol treatment achieved loss of reflexes or responsiveness, and all remained normal upon return to nonmedicated water. Isoflurane emulsified in water produces nonresponsiveness that is appropriate for the first step of euthanasia, while propofol was insufficient at these treatment doses.

Dorsal raphe nucleus to basolateral amygdala 5-HTergic neural circuit modulates restoration of consciousness during sevoflurane anesthesia.

The advent of general anesthesia (GA) has significant implications for clinical practice. However, the exact mechanisms underlying GA-induced transitions in consciousness remain elusive. Given some similarities between GA and sleep, the sleep-arousal neural nuclei and circuits involved in sleep-arousal, including the 5-HTergic system, could be implicated in GA. Herein, we utilized pharmacology, optogenetics, chemogenetics, fiber photometry, and retrograde tracing to demonstrate that both endogenous and exogenous activation of the 5-HTergic neural circuit between the dorsal raphe nucleus (DR) and basolateral amygdala (BLA) promotes arousal and facilitates recovery of consciousness from sevoflurane anesthesia. Notably, the 5-HT1A receptor within this pathway holds a pivotal role. Our findings will be conducive to substantially expanding our comprehension of the neural circuit mechanisms underlying sevoflurane anesthesia and provide a potential target for modulating consciousness, ultimately leading to a reduction in anesthetic dose requirements and side effects.

Volatile Anesthetic Use Versus Total Intravenous Anesthesia for Patients Undergoing Heart Valve Surgery: A Nationwide Population-Based Study.

BACKGROUND: Many studies have suggested that volatile anesthetic use may improve postoperative outcomes after cardiac surgery compared to total intravenous anesthesia (TIVA) owing to its potential cardioprotective effect. However, the results were inconclusive, and few studies have included patients undergoing heart valve surgery. METHODS: This nationwide population-based study included all adult patients who underwent heart valve surgery between 2010 and 2019 in Korea based on data from a health insurance claim database. Patients were divided based on the use of volatile anesthetics: the volatile anesthetics or TIVA groups. After stabilized inverse probability of treatment weighting (IPTW), the association between the use of volatile anesthetics and the risk of cumulative 1-year all-cause mortality (the primary outcome) and cumulative long-term (beyond 1 year) mortality were assessed using Cox regression analysis. RESULTS: Of the 30,755 patients included in this study, the overall incidence of 1-year mortality was 8.5%. After stabilized IPTW, the risk of cumulative 1-year mortality did not differ in the volatile anesthetics group compared to the TIVA group (hazard ratio, 0.98; 95% confidence interval, 0.90-1.07; P = .602), nor did the risk of cumulative long-term mortality (hazard ratio, 0.98; 95% confidence interval, 0.93-1.04; P = .579) at a median (interquartile range) follow-up duration of 4.8 (2.6-7.6) years. CONCLUSIONS: Compared with TIVA, volatile anesthetic use was not associated with reduced postoperative mortality risk in patients undergoing heart valve surgery. Our findings indicate that the use of volatile anesthetics does not have a significant impact on mortality after heart valve surgery. Therefore, the choice of anesthesia type can be based on the anesthesiologists' or institutional preference and experience.

Different narcotic gases and concentrations for immobilization of ostrich embryos for in-ovo imaging.

In-ovo imaging using avian eggs has been described as a potential alternative to animal testing using rodents. However, imaging studies are hampered by embryonal motion producing artifacts. This study aims at systematically comparing isoflurane, desflurane and sevoflurane in three different concentrations in ostrich embryos. Biomagnetic signals of ostrich embryos were recorded analyzing cardiac action and motion. Ten groups comprising eight ostrich embryos each were investigated: Control, isoflurane (2%, 4%, and 6%), desflurane (6%, 12%, and 18%) and sevoflurane (3%, 5%, and 8%). Each ostrich egg was exposed to the same narcotic gas and concentration on development day (DD) 31 and 34. Narcotic gas exposure was upheld for 90 min and embryos were monitored for additional 75 min. Toxicity was evaluated by verifying embryo viability 24 h after the experiments. Initial heart rate of mean 148 beats/min (DD 31) and 136 beats/min (DD 34) decreased over time by 44-48 beats/minute. No significant differences were observed between groups. All narcotic gases led to distinct movement reduction after mean 8 min. Embryos exposed to desflurane 6% showed residual movements. Isoflurane 6% and sevoflurane 8% produced motion-free time intervals of mean 70 min after discontinuation of narcotic gas exposure. Only one embryo death occurred after narcotic gas exposure with desflurane 6%. This study shows that isoflurane, desflurane and sevoflurane are suitable for ostrich embryo immobilization, which is a prerequisite for motion-artifact free imaging. Application of isoflurane 6% and sevoflurane 8% is a) safe as no embryonal deaths occurred after exposure and b) effective as immobilization was observed for approx. 70 min after the end of narcotic gas exposure. These results should be interpreted with caution regarding transferability to other avian species as differences in embryo size and incubation duration exist.

Effect of desflurane anesthesia on flash visual evoked potential monitoring in patients undergoing spine surgery: study protocol for a randomized controlled trial.

BACKGROUND: Flash visual evoked potentials (FVEPs) are a reliable method for protecting visual function during spine surgery in prone position. However, the popularization and application of FVEPs remain limited due to the unclear influence of various anesthetics on FVEPs. Exploring the effects of anesthetic drugs on FVEP and establishing appropriate anesthesia maintenance methods are particularly important for promoting and applying FVEP. According to the conventional concept, inhaled narcotic drugs significantly affect the success of FVEP monitoring, FVEP extraction, and interpretation. Nonetheless, our previous study demonstrated that sevoflurane-propofol balanced anesthesia was a practicable regimen for FVEPs. Desflurane is widely used in general anesthesia for its rapid recovery properties. As the effect of desflurane on FVEP remains unclear, this trial will investigate the effect of different inhaled concentrations of desflurane anesthesia on amplitude of FVEPs during spine surgery, aiming to identify more feasible anesthesia schemes for the clinical application of FVEP. METHODS/ DESIGN: A total of 70 patients undergoing elective spinal surgery will be enrolled in this prospective, randomized controlled, open-label, patient-assessor-blinded, superiority trial and randomly assigned to the low inhaled concentration of desflurane group (LD group) maintained with desflurane-propofolremifentanil-balanced anesthesia or high inhaled concentration of desflurane group (HD group) maintained with desflurane-remifentanil anesthesia maintenance group at a ratio of 1:1. All patients will be monitored for intraoperative FVEPs, and the baseline will be measured half an hour after induction under total intravenous anesthesia (TIVA). After that, patients will receive 0.5 minimum alveolar concentration (MAC) of desflurane combined with propofol and remifentanil for anesthesia maintenance in the LD group, while 0.7-1.0 MAC of desflurane and remifentanil will be maintained in the HD group. The primary outcome is the N75-P100 amplitude 1 h after the induction of anesthesia. We intend to use the dual measure evaluation, dual data entry, and statistical analysis by double trained assessors to ensure the reliability and accuracy of the results. DISCUSSION: This randomized controlled trial aims to explore the superiority effect of low inhaled concentration of desflurane combined with propofolremifentanil-balanced anesthesia versus high inhaled concentration of desflurane combined with remifentanil anesthesia on amplitude of FVEPs. The study is meant to be published in a peer-reviewed journal and might guide the anesthetic regimen for FVEPs. The conclusion is expected to provide high-quality evidence for the effect of desflurane on FVEPs and aim to explore more feasible anesthesia schemes for the clinical application of FVEPs and visual function protection. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov on July 15, 2022. CLINICALTRIALS: gov Identifier: NCT05465330.

GABAergic neurons of anterior thalamic reticular nucleus regulate states of consciousness in propofol- and isoflurane-mediated general anesthesia.

BACKGROUND: The thalamus system plays critical roles in the regulation of reversible unconsciousness induced by general anesthetics, especially the arousal stage of general anesthesia (GA). But the function of thalamus in GA-induced loss of consciousness (LOC) is little known. The thalamic reticular nucleus (TRN) is the only GABAergic neurons-composed nucleus in the thalamus, which is composed of parvalbumin (PV) and somatostatin (SST)-expressing GABAergic neurons. The anterior sector of TRN (aTRN) is indicated to participate in the induction of anesthesia, but the roles remain unclear. This study aimed to reveal the role of the aTRN in propofol and isoflurane anesthesia. METHODS: We first set up c-Fos straining to monitor the activity variation of aTRNPV and aTRNSST neurons during propofol and isoflurane anesthesia. Subsequently, optogenetic tools were utilized to activate aTRNPV and aTRNSST neurons to elucidate the roles of aTRNPV and aTRNSST neurons in propofol and isoflurane anesthesia. Electroencephalogram (EEG) recordings and behavioral tests were recorded and analyzed. Lastly, chemogenetic activation of the aTRNPV neurons was applied to confirm the function of the aTRN neurons in propofol and isoflurane anesthesia. RESULTS: c-Fos straining showed that both aTRNPV and aTRNSST neurons are activated during the LOC period of propofol and isoflurane anesthesia. Optogenetic activation of aTRNPV and aTRNSST neurons promoted isoflurane induction and delayed the recovery of consciousness (ROC) after propofol and isoflurane anesthesia, meanwhile chemogenetic activation of the aTRNPV neurons displayed the similar effects. Moreover, optogenetic and chemogenetic activation of the aTRN neurons resulted in the accumulated burst suppression ratio (BSR) during propofol and isoflurane GA, although they represented different effects on the power distribution of EEG frequency. CONCLUSION: Our findings reveal that the aTRN GABAergic neurons play a critical role in promoting the induction of propofol- and isoflurane-mediated GA.

Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine.

Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.

Isoflurane-induced neuroinflammation and NKCC1/KCC2 dysregulation result in long-term cognitive disorder in neonatal mice.

BACKGROUND: The inhalational anesthetic isoflurane is commonly utilized in clinical practice, particularly in the field of pediatric anesthesia. Research has demonstrated its capacity to induce neuroinflammation and long-term behavioral disorders; however, the underlying mechanism remains unclear [1]. The cation-chloride cotransporters Na+-K+-2Cl--1 (NKCC1) and K+-2Cl--2 (KCC2) play a pivotal role in regulating neuronal responses to gamma-aminobutyric acid (GABA) [2]. Imbalances in NKCC1/KCC2 can disrupt GABA neurotransmission, potentially leading to neural circuit hyperexcitability and reduced inhibition following neonatal exposure to anesthesia [3]. Therefore, this study postulates that anesthetics have the potential to dysregulate NKCC1 and/or KCC2 during brain development. METHODS: We administered 1.5% isoflurane anesthesia to neonatal rats for a duration of 4 h at postnatal day 7 (PND7). Anxiety levels were assessed using the open field test at PND28, while cognitive function was evaluated using the Morris water maze test between PND31 and PND34. Protein levels of NKCC1, KCC2, BDNF, and phosphorylated ERK (P-ERK) in the hippocampus were measured through Western blotting analysis. Pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α were quantified using ELISA. RESULTS: We observed a decrease in locomotion trajectories within the central region and a significantly shorter total distance in the ISO group compared to CON pups, indicating that isoflurane induces anxiety-like behavior. In the Morris water maze (MWM) test, rats exposed to isoflurane exhibited prolonged escape latency onto the platform. Additionally, isoflurane administration resulted in reduced time spent crossing in the MWM experiment at PND34, suggesting long-term impairment of memory function. Furthermore, we found that isoflurane triggered activation of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α; downregulated KCC2/BDNF/P-ERK expression; and increased the NKCC1/KCC2 ratio in the hippocampus of PND7 rats. Bumetadine (NKCC1 specific inhibitors) reversed cognitive damage and effective disorder induced by isoflurane in neonatal rats by inhibiting TNF-α activation, normalizing IL-6 and IL-1ß levels, restoring KCC2 expression levels as well as BDNF and ERK signaling pathways. Based on these findings, it can be speculated that BDNF, P-ERK, IL-1ß, IL-6 and TNF - α may act downstream of the NKCC1/KCC2 pathway. CONCLUSIONS: Our findings provide evidence that isoflurane administration in neonatal rats leads to persistent cognitive deficits through dysregulation of the Cation-Chloride Cotransporters NKCC1 and KCC2, BDNF, p-ERK proteins, as well as neuroinflammatory processes.

Comparison of anaesthesia strategies on postoperative nausea and vomiting in laparoscopic sleeve gastrectomy: a randomised controlled trial.

BACKGROUND: Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy. METHODS: A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h. RESULTS: Postoperative nausea and vomiting assessment at 0-3 h post-surgery revealed no significant differences between groups. However, at 3-24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group. CONCLUSIONS: The incidence and severity of postoperative nausea and vomiting 3-24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021).

Analysis of cardiohemodynamic and electrophysiological effects of morphine along with its toxicokinetic profile using the halothane-anesthetized dogs.

Although morphine has been used for treatment-resistant dyspnea in end-stage heart failure patients, information on its cardiovascular safety profile remains limited. Morphine was intravenously administered to halothane-anesthetized dogs (n=4) in doses of 0.1, 1 and 10 mg/kg/10 min with 20 min of observation period. The low and middle doses attained therapeutic (0.13 µg/mL) and supratherapeutic (0.97 µg/mL) plasma concentrations, respectively. The low dose hardly altered any of the cardiovascular variables except that the QT interval was prolonged for 10-15 min after its start of infusion. The middle dose reduced the preload and afterload to the left ventricle for 5-15 min, then decreased the left ventricular contractility and mean blood pressure for 10-30 min, and finally suppressed the heart rate for 15-30 min. Moreover, the middle dose gradually but progressively prolonged the atrioventricular conduction time, QT interval/QTcV, ventricular late repolarization period and ventricular effective refractory period without altering the intraventricular conduction time, ventricular early repolarization period or terminal repolarization period. A reverse-frequency-dependent delay of ventricular repolarization was confirmed. The high dose induced cardiohemodynamic collapse mainly due to vasodilation in the initial 2 animals by 1.9 and 3.3 min after its start of infusion, respectively, which needed circulatory support to treat. The high dose was not tested further in the remaining 2 animals. Thus, intravenously administered morphine exerts a rapidly appearing vasodilator action followed by slowly developing cardiosuppressive effects. Morphine can delay the ventricular repolarization possibly through IKr inhibition in vivo, but its potential to develop torsade de pointes will be small.

Isoflurane anesthesia and sleep deprivation trigger delayed and selective sleep alterations.

Isoflurane anesthesia (IA) partially compensates NREM sleep (NREMS) and not REM sleep (REMS) requirement, eliciting post-anesthetic REMS rebound. Sleep deprivation triggers compensatory NREMS rebounds and REMS rebounds during recovery sleep as a result of the body's homeostatic mechanisms. A combination of sleep deprivation and isoflurane anesthesia is common in clinical settings, especially prior to surgeries. This study investigates the effects of pre-anesthetic sleep deprivation on post-anesthetic sleep-wake architecture. The effects of isoflurane exposure (90 min) alone were compared with the effects of isoflurane exposure preceded by experimental sleep deprivation (6 h, gentle handling) on recovery sleep in adult mice by studying the architecture of post-anesthetic sleep for 3 consecutive post-anesthetic days. Effects of isoflurane anesthesia on recovery sleep developed only during the first dark period after anesthesia, the active phase in mice. During this time, mice irrespective of preceding sleep pressure, showed NREMS and REMS rebound and decreased wakefulness during recovery sleep. Additionally, sleep deprivation prior to isoflurane treatment caused a persistent reduction of theta power during post-anesthetic REMS at least for 3 post-anesthetic days. We showed that isoflurane causes NREMS rebound during recovery sleep which suggests that isoflurane may not fully compensate for natural NREMS. The study also reveals that isoflurane exposure preceded by sleep deprivation caused a persistent disruption of REMS quality. We suggest that preoperative sleep deprivation may impair postoperative recovery through lasting disruption in sleep quality.