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.

Activation of Orexinergic Neurons Inhibits the Anesthetic Effect of Desflurane on Consciousness State via Paraventricular Thalamic Nucleus in Rats.

BACKGROUND: Orexin, a neuropeptide derived from the perifornical area of the hypothalamus (PeFLH), promotes the recovery of propofol, isoflurane, and sevoflurane anesthesias, without influencing the induction time. However, whether the orexinergic system also plays a similar role in desflurane anesthesia, which is widely applied in clinical practice owing to its most rapid onset and offset time among all volatile anesthetics, has not yet been studied. In the present study, we explored the effect of the orexinergic system on the consciousness state induced by desflurane anesthesia. METHODS: The c-Fos staining was used to observe the activity changes of orexinergic neurons in the PeFLH and their efferent projection regions under desflurane anesthesia. Chemogenetic and optogenetic techniques were applied to compare the effect of PeFLH orexinergic neurons on the induction, emergence, and maintenance states between desflurane and isoflurane anesthesias. Orexinergic terminals in the paraventricular thalamic nucleus (PVT) were manipulated with pharmacologic, chemogenetic, and optogenetic techniques to assess the effect of orexinergic circuitry on desflurane anesthesia. RESULTS: Desflurane anesthesia inhibited the activity of orexinergic neurons in the PeFLH, as well as the neuronal activity in PVT, basal forebrain, dorsal raphe nucleus, and ventral tegmental area, as demonstrated by c-Fos staining. Activation of PeFLH orexinergic neurons prolonged the induction time and accelerated emergence from desflurane anesthesia but only influenced the emergence in isoflurane anesthesia, as demonstrated by chemogenetic and pharmacologic techniques. Meanwhile, optical activation of orexinergic neurons exhibited a long-lasting inhibitory effect on burst-suppression ratio (BSR) under desflurane anesthesia, and the effect may be contributed by the orexinergic PeFLH-PVT circuitry. The orexin-2 receptor (OX2R), but not orexin-1 receptor (OX1R), in the PVT, which had been inhibited most significantly by desflurane, mediated the proemergence effect of desflurane anesthesia. CONCLUSIONS: We discovered, for the first time, that orexinergic neurons in the PeFLH could not only influence the maintenance and emergence from isoflurane and desflurane anesthesias but also affect the induction under desflurane anesthesia. Furthermore, this specific effect is probably mediated by orexinergic PeFLH-PVT circuitry, especially OX2Rs in the PVT.

Increasing hemoglobin concentration with an artificial oxygen carrier improves severe anemia-induced degraded cognitive function.

ABSTRACT: Before death, patients commonly experience impaired consciousness for a significant period, frequently preventing family and others from final interactions with the patient. Some of these episodes of cognitive impairment may be treatable, with treatment not offered owing to the perception of ultimate futility or expense, or both. One of the causes of terminal loss of consciousness or decreased lucidity can be inadequate cerebral oxygen delivery. We report five cases from four institutions where an infusion of a hemoglobin-based oxygen carrier to patients who were unconscious or not lucid owing to acute severe anemia (hemoglobin range, 2.1-5.2 g/dL) resulted in awakening or lucidity. We review briefly human cognitive function and anemia and remark about the use of a hemoglobin-based oxygen carrier for acute severe anemia when red cell transfusion is not an option.

The why behind the high: determinants of neurocognition during acute cannabis exposure.

Acute cannabis intoxication may induce neurocognitive impairment and is a possible cause of human error, injury and psychological distress. One of the major concerns raised about increasing cannabis legalization and the therapeutic use of cannabis is that it will increase cannabis-related harm. However, the impairing effect of cannabis during intoxication varies among individuals and may not occur in all users. There is evidence that the neurocognitive response to acute cannabis exposure is driven by changes in the activity of the mesocorticolimbic and salience networks, can be exacerbated or mitigated by biological and pharmacological factors, varies with product formulations and frequency of use and can differ between recreational and therapeutic use. It is argued that these determinants of the cannabis-induced neurocognitive state should be taken into account when defining and evaluating levels of cannabis impairment in the legal arena, when prescribing cannabis in therapeutic settings and when informing society about the safe and responsible use of cannabis.

Changes in electroencephalographic power and bicoherence spectra according to depth of dexmedetomidine sedation in patients undergoing spinal anesthesia.

Background: Assessment the depth of dexmedetomidine sedation using electroencephalographic (EEG) features can improve the quality of procedural sedation. Previous volunteer studies of dexmedetomidine-induced EEG changes need to be validated, and changes in bicoherence spectra during dexmedetomidine sedation has not been revealed yet. We aimed to investigate the dexmedetomidine-induced EEG change using power spectral and bicoherence analyses in the clinical setting. Patients and Methods: Thirty-six patients undergoing orthopedic surgery under spinal anesthesia were enrolled in this study. Dexmedetomidine sedation was conducted by the stepwise increase in target effect site concentration (Ce) while assessing sedation levels. Bispectral index (BIS) and frontal electroencephalography were recorded continuously, and the performance of BIS and changes in power and bicoherence spectra were analyzed with the data from the F3 electrode. Results: The prediction probability values for detecting different sedation levels were 0.847, 0.841, and 0.844 in BIS, 95% spectral edge frequency, and dexmedetomidine Ce, respectively. As the depth of sedation increased, δ power increased, but high ß and γ power decreased significantly (P <0.001). α and spindle power increased significantly under light and moderate sedation (P <0.001 in light vs baseline and deep sedation; P = 0.002 and P <0.001 in moderate sedation vs baseline and deep sedation, respectively). The bicoherence peaks of the δ and α-spindle regions along the diagonal line of the bicoherence matrix emerged during moderate and deep sedation. Peak bicoherence in the δ area showed sedation-dependent increases (29.93%±7.38%, 36.72%±9.70%, 44.88%±12.90%; light, moderate, and deep sedation; P = 0.008 and P <0.001 in light sedation vs moderate and deep sedation, respectively; P = 0.007 in moderate sedation vs deep sedation), whereas peak bicoherence in the α-spindle area did not change (22.92%±4.90%, 24.72%±4.96%, and 26.96%±8.42%, respectively; P=0.053). Conclusions: The increase of δ power and the decrease of high-frequency power were associated with the gradual deepening of dexmedetomidine sedation. The δ bicoherence peak increased with increasing sedation level and can serve as an indicator reflecting dexmedetomidine sedation levels.

Can changes in skin impedance be used to monitor sedation after midazolam and during recovery from anesthesia?

It has been suggested that sympathetic activity, measured as changes in electrical skin impedance (SI), can be used to assess the adequacy of general anesthesia. Our prospective study investigated if measurements of skin impedance can determine levels of sedation induced by midazolam. Twenty-seven patients scheduled for arthroscopy requiring general anesthesia were served as their own control. These were blinded to the order of injections by telling them that they will be randomly administered a placebo (saline) orsedative agent. A DM 3900 multimeter was used for SI measurements. The degree of sedation was measured using the modified Observer's Assessment of Alertness and Sedation (mOAAS) scale. Resting SI values were noted, and all participants were then administered the placebo followed 5 min later by midazolam 2 mg i.v. Five min after that, patients were administered standard general anesthesia with propofol, oxygen, nitrous oxide 60 %, and isoflurane 1 MAC via a laryngeal mask, and sufentanil 5 - 10 µg. SI significantly increased after administration of midazolam and induction of anesthesia. There were no significant differences between pre-administration (baseline) and placebo and end of surgery and end of anesthesia with closed eyes. There were highly significant differences (p<0.001) between pre-administration vs. midazolam, placebo vs. midazolam, pre-administration vs. induction of anesthesia. We found slight correlation between mOAAS and SI. There were no significant changes between the end of surgery and the end of anesthesia with closed eyes, but SI significantly decreased (p<0.01) after eyes opened.

Repetitive Anodal Transcranial Direct Current Stimulation Hastens Isoflurane-Induced Emergence and Recovery and Enhances Memory in Healthy Rats.

BACKGROUND: Attaining a rapid and smooth return to consciousness after general anesthesia is a goal for clinical anesthesiologists. This study aimed to investigate the effects of repeated anodal transcranial direct current stimulation (atDCS) on emergence and recovery from isoflurane anesthesia in rats. METHODS: Four days after surgery for atDCS socket implantation, rats received either sham stimulation or repetitive anodal direct electrical current of 0.2 mA intensity applied to the right motor cortex for 20 minutes/d for 10 consecutive days. Isoflurane potency and emergence and recovery from a 2-hour isoflurane challenge were evaluated 24 hours after the last atDCS session. Cognitive performance on novel object recognition and spontaneous alternation Y-maze tests were measured 48 hours after the last atDCS session. Locomotor activity was assessed via automated counting of electric infrared beam crossings. RESULTS: Data are expressed as mean ± standard error of mean (SEM). Isoflurane potency was not affected by atDCS (sham: 1.69% ± 0.06%, transcranial direct current stimulation [tDCS]: 1.73% ± 0.11%, mean difference [MD]: 0.045, 95% confidence interval [CI]: -0.22 to 0.30; P = .72). However, the time to appearance of emergence behavioral marker (eg, return of righting reflex) was hastened in rats receiving atDCS (sham: 486 ± 31 seconds, tDCS: 330 ± 45 seconds, MD: 157, 95% CI: 30-284; P = .008). Similarly, time to acknowledgment of adhesive tape ("sticky dot" applied while anesthetized) was also decreased in atDCS-treated rats as compared to sham (sham: 1374 ± 179 seconds, tDCS: 908 ± 151 seconds, MD: 466, 95% CI: 73-858; P = .015), indicating a faster recovery of isoflurane anesthesia. Rats treated with atDCS spent more time exploring the novel object and environment when compared to sham without affecting activity cycles, indicating visual and working memory can be enhanced by atDCS. CONCLUSIONS: Taken together, our findings suggest that atDCS over cortical areas might hasten recovery from isoflurane anesthesia and could potentially be used as a preventative strategy for disruptions in higher order functions related to sedation/anesthesia.

Stunning of pigs with different gas mixtures: Behavioural and physiological reactions.

The present study used thirty-one pigs to investigate induction of unconsciousness and behavioural reactions in different gas mixtures: 80% CO2/air, 90 s; 40% CO2/30% O2/air, 180 s; 70% N2O/30% CO2, 90 s. All pigs lost consciousness. All presented respiratory difficulties and most pigs involuntary muscle contractions, often before loss of standing posture. Between mixtures, average latencies of certain behaviours and delays between behaviours differed. Following immersion, blood pH was lower than normal. The low pH induced by the CO2/O2/air mixture was physiologically associated with hyperoxemia. Relationships between blood gases, different behavioural and heart rate responses are discussed. In conclusion, all mixtures caused discomfort due to respiratory difficulties and the addition of O2 or N2O to the CO2 mixture did not present an advantage.

Anesthetic Potency of Intravenous Infusion of 20% Emulsified Sevoflurane and Effect on the Blood-Gas Partition Coefficient in Dogs.

BACKGROUND: Intravenous (IV) infusions of volatile anesthetics in lipid emulsion may increase blood lipid concentration, potentially altering the anesthetic agent's blood solubility and blood-gas partition coefficient (BGPC). We examined the influence of a low-lipid concentration 20% sevoflurane emulsion on BGPC, and the anesthetic potency of this emulsion using dogs. METHODS: We compared BGPC and anesthetic characteristics in 6 dogs between the IV anesthesia of emulsion and the sevoflurane inhalation anesthesia in a randomized crossover substudy. Minimum alveolar concentrations (MACs) were determined by tail-clamp stimulation by using the up-and-down method. Blood sevoflurane concentration and partial pressure were measured by gas chromatography; end-tidal sevoflurane concentration was measured using a gas monitor. The primary outcome was BGPC at the end of IV anesthesia and inhalation anesthesia. Secondary outcomes were time to loss/recovery of palpebral reflex, finish intubation and awakening, MAC, blood concentration/partial pressure at MAC and awakening, correlation between blood partial pressure and gas monitor, and the safety of emulsions. RESULTS: BGPC showed no difference between IV and inhaled anesthesia (0.859 [0.850-0.887] vs 0.813 [0.791-0.901]; P = .313). Induction and emergence from anesthesia were more rapid in IV anesthesia of emulsion than inhalation anesthesia. MAC of emulsion (1.33% [1.11-1.45]) was lower than that of inhalation (2.40% [2.33-2.48]; P = .031), although there was no significant difference in blood concentration. End-tidal sevoflurane concentration could be estimated using gas monitor during IV anesthesia of emulsion. No major complications were observed. CONCLUSIONS: IV anesthesia with emulsion did not increase the BGCP significantly compared to inhalation anesthesia. It was suggested that the anesthetic potency of this emulsion may be equal to or more than that of inhalation.

Neuroprotective Role of Oral Vitamin D Supplementation on Consciousness and Inflammatory Biomarkers in Determining Severity Outcome in Acute Traumatic Brain Injury Patients: A Double-Blind Randomized Clinical Trial.

BACKGROUND AND OBJECTIVE: Early management of traumatic brain injury (TBI) is essential. We aimed to evaluate the efficacy of vitamin D over early clinical outcome and serum cytokine levels in patients with moderate to severe brain injury. METHODS: Thirty-five patients with moderate to severe traumatic brain injury who were admitted to the ICU unit were recruited into the study. Subjects were randomly allocated to a treatment regimen comprising either a one-time oral dose of 120,000 IU (two tablets of 60,000 IU each) of vitamin D (n = 20) or 8 mg of saccharide (two tablets of 4 g each) as placebo (n = 15). The main parameters evaluated included duration of mechanical ventilation and ICU stay, Glasgow Coma Scale (GCS) and cytokine levels (interleukin (IL)-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ, IL-2). RESULTS: The results indicated an improvement in the level of consciousness after 7 days in the vitamin D-treated group compared with placebo. An elevation in GCS score by 3.86 units in the vitamin D-treated group with a 0.19-unit descent in the control group was recorded. Duration of mechanical ventilation was reduced in the vitamin D-treated group compared with the control group (4.7 days vs. 8.2 days, p value 0.0001). A noticeable reduction was recorded in inflammatory biomarkers (cytokines) in the vitamin D-treated group (IL-6 p = 0.08, TNF-α p = 0.02, IL-2 p = 0.36) with notable elevation in IFN-γ (p = 0.65) compared to the control group. CONCLUSION: In the acute phase of moderate to severe traumatic brain injury, vitamin D supplementation plays a vital role and has a favourable effect on the consciousness level of patients. Clinical trial Registry (CTRI) No. CTRI/2019/05/019259.

The effect of hypothermia during cardiopulmonary bypass on three electro-encephalographic indices assessing analgesia and hypnosis during anesthesia: consciousness index, nociception index, and bispectral index.

The depth of anesthesia is commonly assessed in clinical practice by the patient's clinical signs. However, during cardiopulmonary bypass and hypothermia, common symptoms of nociception such as tachycardia, hypertension, sweating, or movement have low sensitivity and specificity in the description of the patient nociception and hypnosis, in particular, detecting nociceptive stimuli. Better monitoring of the depth of analgesia during hypothermia under cardiopulmonary bypass will avoid underdosage or overdosage of analgesia, especially opioids. Induced hypothermia has a multifactorial effect on the level of analgesia and hypnosis. Thermoregulatory processes appear essential for the activation of analgesic mechanisms, ranging from a physiological strong negative affiliation between nerve conduction velocity and temperature, until significant repercussions on the pharmacological dynamics of the analgesic drugs, the latter decreasing the clearance rate with a subsequent increase in the effect-site concentrations. Under the hypothesis that deep hypothermia induces massive effects on the analgesia and hypnosis levels of the patient, we studied whether hypothermia effects were mirrored by several neuromonitoring indices: two hypnosis indices, consciousness index and bispectral index, and a novel nociception index designed to evaluate the analgesic depth. In this clinical trial, 39 patients were monitored during general anesthesia with coronary atherosclerosis cardiopathy who were elective for on-pump coronary artery bypass graft surgery under hypothermia. The changes and correlation between the consciousness index, bispectral index, and nociception index with respect to the temperature were compared in different timepoints at basic state, during cardiopulmonary bypass and after cardiopulmonary bypass. While the three neuromonitoring indices showed significant correlations with respect to the temperature, the nociception index and consciousness index showed the strongest sensitivities, indicating that these two indices could be an important means of intraoperative neuromonitoring during induced hypothermia under cardiopulmonary bypass.

Dexmedetomidine Pharmacokinetics and a New Dosing Paradigm in Infants Supported With Cardiopulmonary Bypass.

BACKGROUND: Dexmedetomidine is increasingly used off-label in infants and children with cardiac disease during cardiopulmonary bypass (CPB) and in the postoperative period. Despite its frequent use, optimal dosing of dexmedetomidine in the setting of CPB has not been identified but is expected to differ from dosing in those not supported with CPB. This study had the following aims: (1) characterize the effect of CPB on dexmedetomidine clearance (CL) and volume of distribution (V) in infants and young children; (2) characterize tolerance and sedation in patients receiving dexmedetomidine; and (3) identify preliminary dosing recommendations for infants and children undergoing CPB. We hypothesized that CL would decrease, and V would increase during CPB compared to pre- or post-CPB states. METHODS: Open-label, single-center, opportunistic pharmacokinetics (PK) and safety study of dexmedetomidine in patients ≤36 months of age administered dexmedetomidine per standard of care via continuous infusion. We analyzed dexmedetomidine PK data using standard nonlinear mixed effects modeling with NONMEM software. We compared model-estimated PK parameters to those from historical patients receiving dexmedetomidine before anesthesia for urologic, lower abdominal, or plastic surgery; after low-risk cardiac or craniofacial surgery; or during bronchoscopy or nuclear magnetic resonance imaging. We investigated the influence of CPB-related factors on PK estimates and used the final model to simulate dosing recommendations, targeting a plasma concentration previously associated with safety and efficacy (0.6 ng/mL). We used the Wilcoxon rank sum test to evaluate differences in dexmedetomidine exposure between infants with hypotension or bradycardia and those who did not develop these adverse events. RESULTS: We collected 213 dexmedetomidine plasma samples from 18 patients. Patients had a median (range) age of 3.3 months (0.1-34.0 months) and underwent CPB for 161 minutes (63-394 minutes). We estimated a CL of 13.4 L/h/70 kg (95% confidence interval, 2.6-24.2 L/h/70 kg) during CPB, compared to 42.1 L/h/70 kg (95% confidence interval, 38.7-45.8 L/h/70 kg) in the historical patients. No specific CPB-related factor had a statistically significant effect on PK. A loading dose of 0.7 µg/kg over 10 minutes before CPB, followed by maintenance infusions through CPB of 0.2 or 0.25 µg/kg/h in infants with postmenstrual ages of 42 or 92 weeks, respectively, maintained targeted concentrations. We identified no association between dexmedetomidine exposure and selected adverse events (P = .13). CONCLUSIONS: CPB is associated with lower CL during CPB in infants and young children compared to those not undergoing CPB. Further study should more closely investigate CPB-related factors that may influence CL.

δ-Oscillation Correlates of Anesthesia-induced Unconsciousness in Large-scale Brain Networks of Human Infants.

BACKGROUND: Functional brain connectivity studies can provide important information about changes in brain-state dynamics during general anesthesia. In adults, γ-aminobutyric acid-mediated agents disrupt integration of information from local to the whole-brain scale. Beginning around 3 to 4 months postnatal age, γ-aminobutyric acid-mediated anesthetics such as sevoflurane generate α-electroencephalography oscillations. In previous studies of sevoflurane-anesthetized infants 0 to 3.9 months of age, α-oscillations were absent, and power spectra did not distinguish between anesthetized and emergence from anesthesia conditions. Few studies detailing functional connectivity during general anesthesia in infants exist. This study's aim was to identify changes in functional connectivity of the infant brain during anesthesia. METHODS: A retrospective cohort study was performed using multichannel electroencephalograph recordings of 20 infants aged 0 to 3.9 months old who underwent sevoflurane anesthesia for elective surgery. Whole-brain functional connectivity was evaluated during maintenance of a surgical state of anesthesia and during emergence from anesthesia. Functional connectivity was represented as networks, and network efficiency indices (including complexity and modularity) were computed at the sensor and source levels. RESULTS: Sevoflurane decreased functional connectivity at the δ-frequency (1 to 4 Hz) in infants 0 to 3.9 months old when comparing anesthesia with emergence. At the sensor level, complexity decreased during anesthesia, showing less whole-brain integration with prominent alterations in the connectivity of frontal and parietal sensors (median difference, 0.0293; 95% CI, -0.0016 to 0.0397). At the source level, similar results were observed (median difference, 0.0201; 95% CI, -0.0025 to 0.0482) with prominent alterations in the connectivity between default-mode and frontoparietal regions. Anesthesia resulted in fragmented modules as modularity increased at the sensor (median difference, 0.0562; 95% CI, 0.0048 to 0.1298) and source (median difference, 0.0548; 95% CI, -0.0040 to 0.1074) levels. CONCLUSIONS: Sevoflurane is associated with decreased capacity for efficient information transfer in the infant brain. Such findings strengthen the hypothesis that conscious processing relies on an efficient system of integrated information transfer across the whole brain.

A comparison of intravenous sugammadex and neostigmine + atropine reversal on time to consciousness during wake-up tests in spinal surgery.

OBJECTIVE: The effect of sugammadex on consciousness is not yet fully understood. This prospective, randomized, double-blind, multicenter study was performed to compare the effects of intravenous (IV) sugammadex and neostigmine + atropine reversals on time-to-consciousness during intraoperative wake-up tests in patients undergoing spinal surgery. SUBJECTS AND METHODS: A total of 66 American Society of Anesthesiologists I-II patients aged 10-25 years undergoing spinal surgery were recruited. In all patients, bispectral index (BIS), motor-evoked potential (MEP), somatosensory-evoked potentials (SSEP), and train-of-four (TOF) scores were monitored. Patients received the same total IV anesthesia protocol with a propofol-remifentanil mixture. Patients were randomly allocated into two groups. During wake-up test, when the TOF count reached 2 (T2), either sugammadex 2 mg.kg-1 in group S or neostigmine 0.04 mg.kg-1 + atropine 0.01 mg.kg-1 in group N were administered. BIS90, SSEP90, MEP90 was recorded when TOF ratio reached 90, whereas time-to-consciousness (Timecons) was recorded when the patient responded to verbal commands. RESULTS: BIS90 (77.4 ± 4.7, 74.8 ± 3.7), SSEP90(36 ± 9.9, 29.7 ± 8.5), and MEP90 (465.3 ± 34.8, 431.3 ± 28.2) values were significantly greater in group S than in group N (P < 0.05 for each variables). Timecons was significantly shorter with sugammadex than with the neostigmine + atropine combination (P < 0.05). CONCLUSION: Using IV sugammadex 2 mg.kg-1 reversal provides faster responses to verbal commands than neostigmine-atropine combination during the intraoperative wake-up test in patients undergoing spinal surgery because the time to consciousness was significantly shorter. This difference was thought to be related with faster return of neuromuscular transmission because the TOF ratio was >0.9 well before return of consciousness in both groups.

The influence of various methods of anesthesia on time of postoperative recovery of patients' conciousness after curettage of uterine cavity.

OBJECTIVE: Introduction: Scientific information sources point to the significant effectiveness of curettage of uterine cavity (CUC) as a diagnostic and treatment mode of gynecologic oncology. Today the anesthesia service is able to satisfy virtually all the requirements of a surgeon and a female patient, however, some institutional factors, as for example postoperative recovery of consciousness, and factors influencing it, remain unaddressed. The aim: to explore the possibilities of influence of different combinations and dosages of medical preparations used to provide monitored anesthesia care of CUC, to change the time of postoperative recovery of patient's consciousness. PATIENTS AND METHODS: Materials and methods: an interview of 96 patients by VAS, studies of cortisol, insulin and glucose levels in blood serum, measurements of time from the end of surgery to the awakening and complete recovery of consciousness and statistical processing of the results have been conducted. RESULTS: Results: A combination of 50 mg of dexketoprofen and half-dose drugs for narcosis can hasten the postoperative wake-up time by 38%, while maintaining dosages can prolong by 37% on the contrary. There is a dose-dependent effect of drugs for narcosis on the time of full post-operative recovery of consciousness. The reduction of their dosages by half can reduce this time by almost 40%. CONCLUSION: Conclusions: the dosage modification of anesthetic drugs and their combinations may have a significant effect on the time of postoperative awaking and complete recovery of consciousness in female patients after CUC. As a result, it has a positive physiological, psychological and social effect.

Modulation of frontal EEG alpha oscillations during maintenance and emergence phases of general anaesthesia to improve early neurocognitive recovery in older patients: protocol for a randomised controlled trial.

BACKGROUND: Postoperative delirium may manifest in the immediate post-anaesthesia care period. Such episodes appear to be predictive of further episodes of inpatient delirium and associated adverse outcomes. Frontal electroencephalogram (EEG) findings of suppression patterns and low proprietary index values have been associated with postoperative delirium and poor outcomes. However, the efficacy of titrating anaesthesia to proprietary index targets for preventing delirium remains contentious. We aim to assess the efficacy of two strategies which we hypothesise could prevent post-anaesthesia care unit (PACU) delirium by maximising the alpha oscillation observed in frontal EEG channels during the maintenance and emergence phases of anaesthesia. METHODS: This is a 2 × 2 factorial, double-blind, stratified, randomised control trial of 600 patients. Eligible patients are those aged 60 years or over who are undergoing non-cardiac, non-intracranial, volatile-based anaesthesia of expected duration of more than 2 h. Patients will be stratified by pre-operative cognitive status, surgery type and site. For the maintenance phase of anaesthesia, patients will be randomised (1:1) to an alpha power-maximisation anaesthesia titration strategy versus standard care avoiding suppression patterns in the EEG. For the emergence phase of anaesthesia, patients will be randomised (1:1) to early cessation of volatile anaesthesia and emergence from an intravenous infusion of propofol versus standard emergence from volatile anaesthesia only. The primary study outcomes are the power of the frontal alpha oscillation during the maintenance and emergence phases of anaesthesia. Our main clinical outcome of interest is PACU delirium. DISCUSSION: This is a largely exploratory study; the extent to which EEG signatures can be modified by titration of pharmacological agents is not known. The underlying concept is maximisation of anaesthetic efficacy by individualised drug titration to a clearly defined EEG feature. The interventions are already clinically used strategies in anaesthetic practice, but have not been formally evaluated. The addition of propofol during the emergence phase of volatile-based general anaesthesia is known to reduce emergence delirium in children; however, the efficacy of this strategy in older patients is not known. TRIAL REGISTRATION: Australian and New Zealand Clinical Trial Registry, ID: 12617001354370 . Registered on 27/09/2017.

Handgrip dynamometry for continuous assessment of volitional control during induction of anesthesia: a prospective observational study.

PURPOSE: Response to commands is the gold standard to assess the level of consciousness during anesthesia induction but it only provides an intermittent, binary measure with low temporal resolution. To overcome these limitations, we combined the object hold method with handgrip dynamometry to continuously record the force applied to hold a dynamometer as a surrogate measure of the level of consciousness during induction of anesthesia. METHODS: Fourteen patients scheduled for elective lumbar surgery and 14 age-matched non-anesthetized controls were enrolled. The subjects held the dynamometer with their dominant hand for as long as possible (patients) or until told to stop (controls). After a one-minute baseline, propofol was infused (1.0 mg·kg-1·min-1) to the patient group until the subject dropped the dynamometer, which defined the object hold time. Three additional patients were also asked intermittently to squeeze the dynamometer during the propofol infusion to determine any retained ability to exert a strong grip despite any grip changes during induction. RESULTS: The mean (standard deviation) object hold time was 115 (22) seconds after the start of the propofol infusion. There was a progressive significant linear decrease (R2 = 0.98; P < 0.001) in dynamometry-determined handgrip force starting approximately 74 seconds before object drop. Age was inversely related to the object hold time (R2 = 0.47, P < 0.01). The three additional propofol induction patients had strong intermittent grip strength despite progressive decreases in the hold force. Of the 17 patients who completed the object hold task (14 with the standard protocol and three with intermittent squeeze requests), 16 (94%; 95% confidence interval, 76 to 99%) did not respond to verbal commands after dropping the dynamometer. CONCLUSION: Handgrip dynamometry can be used to continuously track volitional control during induction of anesthesia while also reliably showing a gradual loss of consciousness. This method could be useful for studies investigating mechanisms of anesthesia.

Etomidate Sedation for Advanced Endoscopic Procedures.

BACKGROUND AND STUDY AIM: Although propofol is widely used for sedation for endoscopic procedures, concerns remain regarding cardiopulmonary adverse events. Etomidate has little effect on the cardiovascular and respiratory systems, but patient satisfaction analysis is lacking. We compared the efficacy and safety of balanced propofol and etomidate sedation during advanced endoscopic procedures. METHODS: As a randomized noninferiority trial, balanced endoscopic sedation was achieved using midazolam and fentanyl, and patients were randomly assigned to receive propofol (BPS) or etomidate (BES) as add-on drug. The main outcomes were sedation efficacy measured on a 10-point visual analog scale (VAS) and safety. RESULTS: In total, 186 patients (94 in the BPS group and 92 in the BES group) were evaluated. BES did not show noninferiority in terms of overall patient satisfaction, with a difference in VAS score of -0.35 (97.5 % confidence interval -1.03 to ∞, p = 0.03). Among endoscopists and nurses, BES showed noninferiority to BPS, with differences in VAS scores of 0.06 and 0.08, respectively. Incidence of cardiopulmonary adverse events was lower in the BES group (27.7 versus 14.1 %, p = 0.023). Hypoxia occurred in 5.3 and 1.1 % of patients in the BPS and BES group (p = 0.211). Myoclonus occurred in 12.1 % (11/92) in the BES group. BES had lower risk of overall cardiopulmonary adverse events (odds ratio 0.401, p = 0.018). CONCLUSIONS: BES was not noninferior to BPS in terms of patient satisfaction. However, BES showed better safety outcomes in terms of cardiopulmonary adverse events.

Multimodal General Anesthesia: Theory and Practice.

Balanced general anesthesia, the most common management strategy used in anesthesia care, entails the administration of different drugs together to create the anesthetic state. Anesthesiologists developed this approach to avoid sole reliance on ether for general anesthesia maintenance. Balanced general anesthesia uses less of each drug than if the drug were administered alone, thereby increasing the likelihood of its desired effects and reducing the likelihood of its side effects. To manage nociception intraoperatively and pain postoperatively, the current practice of balanced general anesthesia relies almost exclusively on opioids. While opioids are the most effective antinociceptive agents, they have undesirable side effects. Moreover, overreliance on opioids has contributed to the opioid epidemic in the United States. Spurred by concern of opioid overuse, balanced general anesthesia strategies are now using more agents to create the anesthetic state. Under these approaches, called "multimodal general anesthesia," the additional drugs may include agents with specific central nervous system targets such as dexmedetomidine and ones with less specific targets, such as magnesium. It is postulated that use of more agents at smaller doses further maximizes desired effects while minimizing side effects. Although this approach appears to maximize the benefit-to-side effect ratio, no rational strategy has been provided for choosing the drug combinations. Nociception induced by surgery is the primary reason for placing a patient in a state of general anesthesia. Hence, any rational strategy should focus on nociception control intraoperatively and pain control postoperatively. In this Special Article, we review the anatomy and physiology of the nociceptive and arousal circuits, and the mechanisms through which commonly used anesthetics and anesthetic adjuncts act in these systems. We propose a rational strategy for multimodal general anesthesia predicated on choosing a combination of agents that act at different targets in the nociceptive system to control nociception intraoperatively and pain postoperatively. Because these agents also decrease arousal, the doses of hypnotics and/or inhaled ethers needed to control unconsciousness are reduced. Effective use of this strategy requires simultaneous monitoring of antinociception and level of unconsciousness. We illustrate the application of this strategy by summarizing anesthetic management for 4 representative surgeries.

The last low whispers of our dead: when is it ethically justifiable to render a patient unconscious until death?

A number of practices at the end of life can causally contribute to diminished consciousness in dying patients. Despite overlapping meanings and a confusing plethora of names in the published literature, this article distinguishes three types of clinically and ethically distinct practices: (1) double-effect sedation, (2) parsimonious direct sedation, and (3) sedation to unconsciousness and death. After exploring the concept of suffering, the value of consciousness, the philosophy of therapy, the ethical importance of intention, and the rule of double effect, these three practices are defined clearly and evaluated ethically. It is concluded that, if one is opposed to euthanasia and assisted suicide, double-effect sedation can frequently be ethically justified, that parsimonious direct sedation can be ethically justified only in extremely rare circumstances in which symptoms have already completely consumed the patient's consciousness, and that sedation to unconsciousness and death is never justifiable. The special case of sedation for existential suffering is also considered and rejected.