In Vivo Photoadduction of Anesthetic Ligands in Mouse Brain Markedly Extends Sedation and Hypnosis.

Photoaffinity ligands are best known as tools used to identify the specific binding sites of drugs to their molecular targets. However, photoaffinity ligands have the potential to further define critical neuroanatomic targets of drug action. In the brains of WT male mice, we demonstrate the feasibility of using photoaffinity ligands in vivo to prolong anesthesia via targeted yet spatially restricted photoadduction of azi-m-propofol (aziPm), a photoreactive analog of the general anesthetic propofol. Systemic administration of aziPm with bilateral near-ultraviolet photoadduction in the rostral pons, at the border of the parabrachial nucleus and locus coeruleus, produced a 20-fold increase in the duration of sedative and hypnotic effects compared with control mice without UV illumination. Photoadduction that missed the parabrachial-coerulean complex also failed to extend the sedative or hypnotic actions of aziPm and was indistinguishable from nonadducted controls. Paralleling the prolonged behavioral and EEG consequences of on target in vivo photoadduction, we conducted electrophysiologic recordings in rostral pontine brain slices. Using neurons within the locus coeruleus to further highlight the cellular consequences of irreversible aziPm binding, we demonstrate transient slowing of spontaneous action potentials with a brief bath application of aziPm that becomes irreversible on photoadduction. Together, these findings suggest that photochemistry-based strategies are a viable new approach for probing CNS physiology and pathophysiology.SIGNIFICANCE STATEMENT Photoaffinity ligands are drugs capable of light-induced irreversible binding, which have unexploited potential to identify the neuroanatomic sites of drug action. We systemically administer a centrally acting anesthetic photoaffinity ligand in mice, conduct localized photoillumination within the brain to covalently adduct the drug at its in vivo sites of action, and successfully enrich irreversible drug binding within a restricted 250 µm radius. When photoadduction encompassed the pontine parabrachial-coerulean complex, anesthetic sedation and hypnosis was prolonged 20-fold, thus illustrating the power of in vivo photochemistry to help unravel neuronal mechanisms of drug action.

Adequacy of maternal anesthesia depth with two sodium thiopental doses in elective caesarean section: a randomized clinical trial.

BACKGROUND: Administration of an optimal dose of anesthetic agent to ensure adequate depth of hypnosis with the lowest risk of adverse effects to the fetus is highly important in cesarean section. Sodium thiopental (STP) is still the first choice for induction of anesthesia in some countries for this obstetric surgery. We aimed to compare two doses of STP with regarding the depth of anesthesia and the condition of newborn infants. METHODS: In this clinical trial, parturient undergoing elective Caesarian section were randomized into two groups receiving either low-dose (5 mg/kg) or high-dose (7 mg/kg) STP. Muscle relaxation was provided with succinylcholine 2 mg/kg and anesthesia was maintained with O2/N2O and sevoflurane. The depth of anesthesia was evaluated using isolated forearm technique (IFT) and bispectral index (BIS) in various phases. Additionally, infants were assessed using Apgar score and neurobehavioral test. RESULTS: Forty parturient were evaluated in each group. BIS was significantly lower in high-dose group at skin incision to delivery and subcutaneous and skin closure. Also, significant differences were noticed in IFT over induction to incision and incision to delivery. Apgar score was significantly lower in high-dose group at 1 min after delivery. Newborn infants in low-dose group had significantly better outcomes in all three domains of the neurobehavioral test. CONCLUSION: 7 mg/kg STP is superior to 5 mg/kg in creating deeper hypnosis for mothers. However, it negatively impacts Apgar score and neurobehavioral test of neonates. STP seems to has dropped behind as an acceptable anesthetic in Cesarean section. TRIAL REGISTRATION: IRCT No: 2016082819470 N45 , 13/03/2019.

Reduced antioxidant and anti-inflammatory effects of propofol at high-dose on morbidly obese patients.

This study was aimed to investigate differences in antioxidant and anti-inflammatory effects of propofol at two commonly used dosing schedules on morbidly obese patients. Twenty-two morbidly obese patients were randomly divided into two groups, namely, TBW (dosing based on total body weight) and LBW (dosing based on lean body weight) groups. Three biomarkers, i.e. superoxide dismutase (SOD), malondialdehyde (MDA) and nitric oxide (NO) were measured as indicators of the level of oxidation stress reaction. Pro-inflammatory cytokines including Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were used to describe the degree of inflammation. Plasma levels of SOD, MDA and NO were increased and reached a peak value 0.5h after anesthesia induction, but the increase was smaller in the LBW group compared with the TBW group. Besides, plasma concentrations of IL-6 and IL-8 were also increased and attained a peak level 0.5h after anesthesia induction, but the increase was higher in the TBW group compared with the LBW group. The LBW-based dosing of propofol had more potent antioxidant and anti-inflammatory effects than the TBW-based dosing during anesthesia induction period on morbidly obese patients. This study provided a dosing recommendation of propofol for morbidly obese patients.

Optimization, and in vitro and in vivo evaluation of etomidate intravenous lipid emulsion.

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, -36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

Modeling an auditory stimulated brain under altered states of consciousness using the generalized Ising model.

Propofol is a short-acting medication that results in decreased levels of consciousness and is used for general anesthesia. Although it is the most commonly used anesthetic in the world, much remains unknown about the mechanisms by which it induces a loss of consciousness. Characterizing anesthesia-induced alterations to brain network activity might provide a powerful framework for understanding the neural mechanisms of unconsciousness. The aim of this work was to model brain activity in healthy brains during various stages of consciousness, as induced by propofol, in the auditory paradigm. We used the generalized Ising model (GIM) to fit the empirical fMRI data of healthy subjects while they listened to an audio clip from a movie. The external stimulus (audio clip) is believed to be at least partially driving a synchronization process of the brain activity and provides a similar conscious experience in different subjects. In order to observe the common synchronization among the subjects, a novel technique called the inter subject correlation (ISC) was implemented. We showed that the GIM-modified to incorporate the naturalistic external field-was able to fit the empirical task fMRI data in the awake state, in mild sedation, in deep sedation, and in recovery, at a temperature T* which is well above the critical temperature. To our knowledge this is the first study that captures human brain activity in response to real-life external stimuli at different levels of conscious awareness using mathematical modeling. This study might be helpful in the future to assess the level of consciousness of patients with disorders of consciousness and help in regaining their consciousness.

Brainwave entrainment to minimise sedative drug doses in paediatric surgery: a randomised controlled trial.

BACKGROUND: Anaesthetic drugs may cause neuroapoptosis in children and are routinely used off-label in specific age groups. Techniques that reduce anaesthetic drug dose requirements in children may thus enhance the safety of paediatric sedation or anaesthesia. Brainwave entrainment, notably in the form of auditory binaural beats, has been shown to have sedative effects in adults. We evaluated the influence of brainwave entrainment on propofol dose requirements for sedation in children. METHODS: We randomised 49 boys scheduled for sub-umbilical surgery under caudal blockade to an entrainment or a control group. Small differences in pitch were applied to each ear to create binaural beats, supplemented by synchronous visual stimuli, within the electroencephalographic frequency bands seen during relaxation and (rapid eye movement/non-rapid eye movement) sleep. After establishment of caudal block, propofol infusion was started at 5 mg kg-1 h-1. Intraoperatively, the infusion rate was adjusted every 5 min depending on the sedation state judged by the bispectral index (BIS). The infusion rate was decreased by 1 mg kg-1 h-1 if BIS was <70, and was increased if BIS was >70, heart rate increased by 20%, or if there were other signs of inadequate sedation. RESULTS: Mean propofol infusion rates were 3.0 (95% confidence interval [CI]: 2.4-3.6) mg kg-1 h-1vs 4.2 (95% CI: 3.6-4.8) mg kg-1 h-1 in the entrainment and control groups, respectively (P<0.01). BIS values were similar in the two groups. CONCLUSIONS: Brainwave entrainment effectively reduced the propofol infusion rates required for sedation in children undergoing surgery with regional anaesthesia. Further studies are needed to investigate the possibility of phasing out propofol infusions completely during longer surgical procedures and optimising the settings of brainwave stimulation. CLINICAL TRIAL REGISTRATION: DRKS00005064.

Virtual reality as an adjunct to anesthesia in the operating room.

BACKGROUND: Advancements in virtual reality (VR) technology have resulted in its expansion into health care. Preliminary studies have found VR to be effective as an adjunct to anesthesia to reduce pain and anxiety for patients during upper gastrointestinal endoscopies, dental procedures and joint arthroplasties. Current standard care practice for upper extremity surgery includes a combination of regional anesthesia and intraoperative propofol sedation. Commonly, patients receive deep propofol sedation during these cases, leading to potentially avoidable risks of over-sedation, hypotension, upper airway obstruction, and apnea. The objective of this study is to evaluate the effectiveness of VR technology to promote relaxation for patients undergoing upper extremity surgery, thereby reducing intraoperative anesthetic requirements and improving the perioperative patient experience. METHODS: In this single-center, randomized controlled trial, 40 adult patients undergoing upper extremity orthopedic surgery will be randomly allocated to either intraoperative VR immersion or usual care. VR immersion is designed to provide patients with a relaxing virtual environment to alleviate intraoperative anxiety. All patients receive a peripheral nerve block prior to surgery. Patients in the intervention group will select videos or immersive environments which will be played in the VR headset during surgery. An anesthesia provider will perform their usual clinical responsibilities intraoperatively and can administer anesthetic medications if and when clinically necessary. Patients in the control arm will undergo perioperative anesthesia according to standard care practice. The primary outcome is the difference in intraoperative propofol dose between the groups. Secondary outcomes include postoperative analgesia requirements and pain scores, length of stay in the postanesthesia care unit, overall patient satisfaction and postoperative functional outcomes. DISCUSSION: It is unknown whether the use of VR during upper extremity surgery can reduce intraoperative anesthetic requirements, reduce perioperative complications, or improve the postoperative patient experience. A positive result from this clinical trial would add to the growing body of evidence that demonstrates the effectiveness of VR as an adjunct to anesthesia in reducing intraoperative pain and anxiety for multiple types of procedure. This could lead to a change in practice, with the introduction of a nonpharmacologic intervention potentially reducing the burden of over-sedation while still providing a satisfactory perioperative experience. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03614325. Registered on 9 July 2018.

Wide-Awake Local Anesthesia No Tourniquet (WALANT) versus Local or Intravenous Regional Anesthesia with Tourniquet in Atraumatic Hand Cases in Orthopedics: A Systematic Review and Meta-Analysis.

Background: To compare outcomes of atraumatic hand surgeries using the WALANT technique versus intravenous regional anesthesia or local anesthesia with tourniquet. Methods: We conducted a comprehensive literature search using PubMed, MEDLINE, Embase, and Cochrane Library from inception to October 2018. All randomized or quasi-randomized trials and cohort studies comparing WALANT procedure versus local anesthesia or intravenous regional anesthesia with tourniquet among atraumatic hand surgeries were included. Methodological quality and risk of bias of eligible studies were assessed by three independent reviewers. The random effects model was used due to both statistical and clinical heterogeneity among studies. Results: The search yielded 496 records, of which 9 studies were included in the systematic review. We were able to pool findings for operative time, post-operative pain scores, patient satisfaction, and complication rates. On the average, the WALANT group had longer operative times by 2.06 minutes (pooled mean difference, random effects, 95% confidence interval 0.46 to 3.67 minutes, p = 0.01, I2 0%, p = 0.66). The post-operative pain scores were lower in the WALANT group by an average of two VAS points (random effects, pooled mean difference -2.40, 95% confidence interval -3.41 to -1.38, p < 0.00001; I2 0% p = 0.99). We had insufficient evidence to demonstrate a difference in terms of patient satisfaction (random effects, pooled risk ratio 0.98, 95% confidence interval 0.93 to 1.03, p = 0.36, I2 0%, p = 0.64) and complication rates (random effects, pooled risk ratio 0.40, 95% confidence interval 0.07 to 2.18, p = 0.29, I2 60% p = 0.08) between WALANT versus conventional methods. Conclusions: The WALANT group reported lower post-operative pain scores, but had slightly longer operative times. There are no significant differences between WALANT and conventional methods in terms of patient satisfaction and complication rates.

Does smoking increase the anesthetic requirement?

Background/aim: To examine the effects of active and passive smoking on perioperative anesthetic and analgesic consumption. Materials and methods: Patients were divided into three groups: group S, smokers; group PS, passive smokers; and group NS, individuals who did not have a history of smoking and were not exposed to smoke. All patients underwent the standard total intravenous anesthesia method. The primary endpoint of this study was determination of the total amount of propofol and remifentanil consumed. Results: The amount of propofol used in induction of anesthesia was significantly higher in group S compared to groups PS and NS. Moreover, the total consumption of propofol was significantly higher in group S compared to groups PS and NS. The total propofol consumption of group PS was significantly higher than that of group NS (P = 0.00). Analysis of total remifentanil consumption showed that remifentanil use was significantly higher in group S compared to group NS (P = 0.00). Conclusion: The amount of the anesthetic required to ensure equal anesthetic depth in similar surgeries was higher in active smokers and passive smokers compared to nonsmokers.

Suppression of Urinary Voiding "on Demand" by High-Frequency Stimulation of the S1 Sacral Nerve Root in Anesthetized Rats.

OBJECTIVES: High-frequency (kHz) stimulation of preganglionic pelvic nerve afferents can inhibit voiding in both anesthetized and conscious rats. The afferents travel via the S1 sacral nerve root, which is easier to access than the distal pelvic nerve fibers within the abdominal cavity. We therefore investigated whether voiding could be inhibited by high-frequency stimulation at S1 and how this compared to distal pelvic nerve stimulation. METHODS: Urethane-anesthetized rats were instrumented to record bladder pressure and abdominal wall electromyogram and to stimulate the distal preganglionic pelvic nerve bundle and S1 sacral root. Saline was infused continuously into the bladder to evoke repeated voiding. Stimulation was initiated within 1-2 sec of the onset of the steep rise in bladder pressure signaling an imminent void. RESULTS: In six rats, stimulation of the distal pelvic nerve bundle (1-3 kHz sinusoidal waveform 1 mA, 60 sec) supressed the occurrence of an imminent void. Voiding resumed within 70 ± 13.0 sec (mean ± SEM) of stopping stimulation. Stimulation (using the same parameters) of the S1 root at the level of the sacral foramen suppressed voiding for the entire stimulation period in three rats and deferred voiding for 35-56 sec (mean 44.0 ± 3.2 sec) in the remaining three. Stimulation at either site when the bladder was approximately half full, as estimated from previous intervoid intervals, had no effect on voiding. CONCLUSIONS: This preliminary study provides proof-of-concept for the sacral root as an accessible target for high-frequency stimulation that may be developed as an "on demand" neuromodulation paradigm to suppress unwanted urinary voids. CONFLICT OF INTEREST: The authors reported no conflict of interest.

Randomised, masked study of local anaesthesia administered prior to external dacryocystorhinostomy under general anaesthesia.

OBJECTIVES: To determine whether administration of local anaesthetic at the site of skin incision during open lacrimal drainage surgery under general anaesthesia alters the total dosage of anaesthetic drugs required during total intravenous anaesthesia (TIVA), and whether it alters postoperative pain and recovery. STUDY DESIGN: Masked comparison of a randomized, two-group interventional study. PATIENTS AND METHODS: Patients undergoing unilateral external dacryocystorhinostomy under total intravenous general anaesthesia were recruited from the lacrimal service at Moorfields Eye Hospital between September 2012 and February 2014. The patients were randomised to receive, after induction and stabilisation of general anaesthesia, infiltration of the ipsilateral paranasal tissues with 2.5 ml of 0.5% bupivacaine with 1:100000 epinephrine ("treatment" group), or a sham injection ("control" group); the infiltration was performed about 7 min prior to the skin incision. The infusion rates for propofol and remifentanil were adjusted to maintain a steady intra-operative mean blood pressure of 55-70 mmHg and BIS score of 40-60%. The time taken for extubation of the patient after cessation of TIVA was recorded, and postoperative pain scores (on a Likert scale from 0-10) were taken at regular intervals after extubation. The average intra-operative mean blood pressures, total drug usage, extubation time and pain scores for each of the two groups were compared using two-tail Student's t-testing and Wilcoxon rank sum testing. RESULTS: There were 12 patients (7 female; 58%) in the treatment group and 11 (7 female; 64%) in the control group, with similar average age at surgery (59 years treatment, 53 years control; p = 0.38) The average operative time was 45 min in the treatment group (median 42, range 30-55) and 47 min (median 45; range 37-61) in the control group (p = 0.52). The mean dosage of propofol required to maintain satisfactory GA was significantly less in the "treatment" group (89.8 mcg/kg/min) as compared to the "control" group (mean 126 mcg/kg/min) (p = 0.0007). Likewise, remifentanil dosage was significantly less in the "treatment" group (100 ng/kg/min) as compared to controls (259 ng/kg/min) (p = 0.00007). The mean non-invasive blood pressure was consistently lower during surgery in the "treated" group, and showed less intra-operative variation. After surgery, the patients receiving LA had a significantly shorter extubation time (mean time 6.0 min in "treated" group, 12.1 min in "controls"; P < 0.0002) and also significantly lower pain scores at 10, 30, 60, 120 and 180 min after extubation (p < 0.01, p < 0.01, p < 0.01, p < 0.01 and p < 0.05, respectively). CONCLUSIONS: Ipsilateral infiltration of local anaesthesia containing epinephrine in the paranasal tissues just prior to open dacryocystorhinostomy under total intravenous anaesthesia is associated with a 28% reduction in mean propofol usage, and a 61% reduction in remifentanil usage. LA usage during GA also produces improved and less variable intra-operative mean blood pressures, a significantly shorter extubation time and significantly lower postoperative pain scores.

Effect of Combined Acupuncture Anesthesia on Surgical Dosage and Serum IL-4, IL-10 of Pneumonectomy Patients.

OBJECTIVE: To analyse the effects of combined acupuncture anesthesia on surgical dosage and serum interleukin-4 (IL-4), interleukin-10 (IL-10) of pneumonectomy patients. STUDY DESIGN: A randomised controlled trial (RCT). PLACE AND DURATION OF STUDY: Lanzhou University Second Hospital, Lanzhou, China, from January 2016 to November 2017. METHODOLOGY: A total of 110 patients undergoing pneumonectomy were randomly divided into group A and group B, with 55 cases in each group. Group A was treated with combined 2Hz acupuncture anesthesia, while group B was treated with combined 2Hz/100Hz acupuncture anesthesia. The additional propofol, fentanyl dosage, and changes in heart rate and systolic blood pressure 5 min before and during extubation were compared between the two groups. The serum IL-4 and IL-10 levels were measured 10 minutes after skin incision and 24 hours after surgery using ELISA. Pain was rated by visual analogue scale (VAS) at 24 hours after surgery. RESULTS: There was no statistically significant difference between group A and group B in the intraoperative additional propofol and fentanyl dosags (p=0.541 and 0.719, respectively). There is no statistical difference in heart rate and systolic blood pressure between group A and group B at 5 minutes before and during extubation (p=0.151, 0.660 and 0.734, 0.528, respectively). There is no statistical difference between group A and group B in serum IL-4 and IL-10 levels 10 minutes after surgical incision (p=0.916 and 0.841, respectively). However, serum IL-4 and IL-2 levels in group A are statistically lower than that of group B at 24 hours after surgery (all p<0.001). The VAS score at 24 hours after surgery in group A was 2.44 ±0.71 points, which was significantly lower than that of group B (3.82 ±0.77 points, p<0.001). CONCLUSION: Combined 2 Hz, 2 Hz/100 Hz acupuncture anesthesia need few anesthetic dosages of propofol and fentanyl to stabilise the patient's blood pressure and heart rate when intubated under general anesthesia; but combined 2 Hz acupuncture anesthesia can reduce IL-4 and IL-10 levels during surgery stress to a greater extent than the latter, and can effectively lower patients' serum IL-4, IL-10 expression after surgery.

Effects of transcutaneous acupoint electrical stimulation combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus: A randomized controlled trial.

BACKGROUND: Myoclonus is an undesirable phenomenon that occurs after induction of general anesthesia using etomidate. Opioids such as sufentanil are considered effective pretreatment drugs for myoclonus inhibition, although high doses are required. Transcutaneous acupoint electrical stimulation (TAES), a noninvasive technique involving electrical stimulation of the skin at the acupuncture points, exhibits analgesic effects, promotes anesthetic effects, decreases the dose of anesthetic drugs, and increases endogenous opioid peptide levels. In the present study, we investigated the effects of TAES combined with low-dose sufentanil pretreatment on the incidence and severity of etomidate-induced myoclonus in patients undergoing elective hysteroscopy. METHODS: In a double-blind manner, 172 patients (American Society of Anesthesiologists class I-II; age, 20-55 years) scheduled to undergo elective hysteroscopy were randomized into the following groups (n = 43 each): control (false TAES followed by saline injection after 30 min), TAES (TAES followed by saline injection after 30 minutes), sufentanil [false TAES followed by low-dose sufentanil (0.1 µg/kg) injection after 30 minutes], and sufentanil plus TAES (TAES followed by low-dose sufentanil injection after 30 minutes). In all groups, general anesthesia was induced by etomidate 0.3 mg/kg after sufentanil or saline injection. The incidence and severity of myoclonus were assessed for 2 minutes after etomidate administration. The visual analogue scale (VAS) scores for pain at 1 hour after surgery were recorded. The heart rate (HR), mean arterial pressure (MAP), and peripheral capillary oxygen saturation (SPO2) were recorded before premedication, after etomidate injection, after uterus expansion, and after recovery from anesthesia. RESULTS: The incidence of myoclonus was highest in the control group (88.3%), followed by TAES (74.4%), sufentanil (60.4%), and TAES plus sufentanil (48.8%) groups. Thus, the incidence was significantly higher in the control and TAES groups than in the sufentanil and TAES plus sufentanil groups. Grade 3 myoclonus occurred in 30.2%, 9.3%, 11.6%, and 9.3% patients in the control, TAES, sufentanil, and TAES plus sufentanil groups, respectively, with significant differences between the control group and the other 3 groups. Furthermore, the postoperative VAS scores for pain were significantly lower in the TAES, sufentanil, and TAES plus sufentanil groups compared with those in the control group. There were no significant differences in any other parameters among groups. CONCLUSION: Our results suggest that TAES combined with low-dose opioids such as sufentanil can decrease the incidence and severity of etomidate-induced myoclonus.

Influence of Depth of Hypnosis on Pupillary Reactivity to a Standardized Tetanic Stimulus in Patients Under Propofol-Remifentanil Target-Controlled Infusion: A Crossover Randomized Pilot Study.

BACKGROUND: Pupillometry allows the measurement of pupillary diameter variations in response to nociceptive stimuli. This technique has been used to monitor the balance between analgesia and nociception. Under general anesthesia, the amplitude of pupillary dilation is related to the amount of administered opioids. The objective of this study was to determine whether at a constant infusion rate of opioids, the pupillary response was influenced by depth of hypnosis assessed by the bispectral index (BIS). METHODS: Twelve patients (14-20 years) anesthetized for orthopedic surgery were included. Under propofol-remifentanil target-controlled infusion, remifentanil effect site target concentration was fixed at 1 ng/mL. Two measures of pupillary reflex dilation were performed on each patient in a randomized order: one at BIS 55 and one at BIS 25. These levels of BIS were obtained by adjusting propofol target concentration and maintained for 10 minutes before each measure. For each measure, we applied a standardized tetanic stimulation on the patient's forearm (60 mA, 100 Hz, 5 seconds). All measures were performed before the beginning of surgery. RESULTS: Pupillary dilation was significantly greater at BIS 55 than at BIS 25: 32.1% ± 5.3% vs 10.4% ± 2.5% (mean difference estimate [95% confidence interval]: 21.8% [12.9-30.6], P < .001), without carryover effect (P = .30) nor period effect (P = .52). Hemodynamic parameters and BIS were not modified by the stimulation. CONCLUSIONS: In patients receiving a constant infusion of remifentanil at a target concentration of 1 ng/mL, pupillary dilation after a standardized tetanic stimulation was influenced by depth of hypnosis assessed by the BIS.

Does a hypnosis session reduce the required propofol dose during closed-loop anaesthesia induction?: A randomised controlled trial.

BACKGROUND: Hypnosis has a positive effect on peri-operative anxiety and pain. OBJECTIVE: The objective of this study was to assess the impact of a formal deep hypnosis session on the consumption of propofol for anaesthetic induction using automated administration of propofol guided by the bispectral index (BIS) in a closed loop. DESIGN: A 1 : 1 randomised, usual-care-controlled, single-centre trial. SETTING: Tertiary care centre in France from April 2014 to December 2015. PATIENTS: Female adult patients scheduled for outpatient gynaecological surgery under general anaesthesia. INTERVENTION: Before surgery, patients were randomised to receive either a deep hypnosis session or routine care. Anaesthetic induction was performed automatically by propofol without opioids and was assisted by the BIS in a closed loop. MAIN OUTCOME MEASURES: The primary endpoint was the propofol dose required for anaesthesia induction, defined as a BIS less than 60 for at least 30 s. RESULTS: Data for 31 patients in the hypnosis group and 35 in the control group were analysed. There was no evidence of a difference in the mean required propofol dose for anaesthetic induction between the hypnosis and the control groups (2.06 mg kg (95% confidence interval [1.68 to 2.43]) versus 1.79 mg kg (95% CI [1.54 to 2.03]), P = 0.25, respectively). CONCLUSION: The current study, which was designed to determine the effect of a deep hypnosis session on anaesthesia induction using an automated tool for propofol administration, failed to detect a difference in the required dose of propofol. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02249364.

[Effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients after target-controlled induction].

OBJECTIVE: To observe the clinical effect of ear point embedding on plasma and effect site concentrations of propofol-remifentanil in elderly patients who underwent abdominal external hernia surgery at the time of consciousness and pain disappearing by target-controlled infusion (TCI) and bispectral index (BIS). METHODS: Fifty patients who underwent elective abdominal hernia surgery were randomly assigned into an observation group and a control group, 25 cases in each one. In the observation group, 30 minutes before anesthesia induction, Fugugou (Extra), Gan (CO12), Pizhixia (AT4), and Shenmen (TF4) were embedded by auricular needles until the end of surgery, 10 times of counter press each point. In the control group, the same amount of auricular tape was applied until the end of surgery at the same points without stimulation 30 minutes before anesthesia induction. Patients in the two groups were given total intravenous anesthesia, and BIS was monitored by BIS anesthesia depth monitor. Propofol was infused by TCI at a beginning concentration of 1.5µg/L and increased by 0.3µg/L every 30s until the patients lost their consciousness. After that, remifentanil was infused by TCI at a beginning concentration of 2.0µg/L and increased by 0.3µg/L every 30s until the patients had no body reaction to pain stimulation (orbital reflex). Indices were recorded, including mean arterial pressure (MAP), heart rate (HR) and the BIS values, at the time of T0 (entering into the operation room), T1 (losing consciousness) and T2 (pain relief), the plasma and effect site concentrations of propofol at T1, the plasma and effect site concentrations of remifentanil at T2. After surgery we recorded the total amounts of propofol and remifentanil, surgery time and anesthesia time. RESULTS: At T1 and T2, MAP and HR of the observation group were higher than those of the control group (P<0.05, P<0.01). At T1, the plasma and effect site concentrations of propofol in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). At T2, the plasma and effect site concentrations of remifentanil in the observation group were significantly lower than those in the control group (P<0.05, P<0.01). There was no significant difference in BIS values at T1 and T2 between the two groups (bothP>0.05). There was no significant difference in operation time and anesthesia time between the two groups (bothP>0.05). The total amount of remifentanil in the observation group was significantly lower than that in the control group (P<0.01). There was no significant difference in the total amount of propofol between the two groups (P>0.05). CONCLUSIONS: Ear points embedding combined with propofol-remifentanil TCI could reduce the plasma and effect site concentrations of propofol and remifentanil and the total amount of remifentanil in elderly patients with extra-abdominal hernia surgery, and had the effect of assisting sedation and analgesia.

[Clinical research of electroacupuncture on the analgesic effect of thoracic perioperative stage].

OBJECTIVE: To discuss the clinical therapeutic effects of electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) on the analgesic effect of thoracic perioperative stage and its effect mechanism. METHODS: Sixty cases of esophageal cancer with elective radical resection under general anesthesia were divided into an observation group and a control group according to the operation sequence, 30 cases in each one. In the control group, the general anesthesia was simply applied and sufentanil was administered for patient controlled intravenous analgesia (PCIA) after operation. In the observation group, on the basis of the scheme as the control group, the electroacupuncture was used at Neimadian (Extra) and Neiguan (PC 6) 30 min before anesthesia induction and after operation, with continuous wave, tolerable intensity, lasting for 30 min. Separately, before acupuncture (T1) and 2h (T2), 12h (T3), 24h (T4) and 48h (T5) after operation, the plasma ß-endorphin (ß-EP), 5-hydroxytryptamine (5-HT) and prostaglandin E2 (PGE2) were determined. During operation, under the same state (from 50 to 60) of bispectrum of EEG (BIS), the intraoperative anesthetic dose was recorded. Using visual analogue scale (VAS), the pain degree was evaluated at T2, T3, T4 and T5 separately and the grade assessment of the therapeutic effects and safety were recorded at each time point. RESULTS: ①The total dosage of sufentanil in the observation group was less than that in the control group[(1.83±0.56) mg vs (2.54±0.62) mg, P<0.05]. ②VAS scores at T2, T3 and T4 in the patients of the observation group were all lower than those in the control group (all P<0.05). ③The levels of plasma ß-EP at T3, T4 and T5 in the observation group were increased significantly as compared with those in the control group (all P<0.05) and the levels of plasma 5-HT and PGE2 at T2, T3 and T4 were reduced significantly as compared with those in the control group (all P<0.05). ④ The excellent analgesia rates 2h、12h and 24h after operation in the observation group were better than those in the control group (all P<0.05). ⑤The rate of the A grade safety in the observation group was higher than that in the control group (P<0.05). CONCLUSIONS: Electroacupuncture at Neimadian (Extra) and Neiguan (PC 6) provides the safe and effective postoperative anesthesia of thoracic surgery and reduces the dosage of analgesics during the operation, which is possibly related to the increase of endogenous ß-EP and the inhibition on the release of 5-HT and PGE2.

Analgesia multimodal y anestesia regional / Multimodal analgesia and regional anaesthesia

La analgesia multimodal permite conseguir una analgesia de calidad y con menos efectos secundarios gracias al uso de diferentes analgésicos o técnicas analgésicas. La anestesia regional juega un papel fundamental para conseguir este objetivo. Las diferentes técnicas de anestesia regional, que incluyen tanto los bloqueos periféricos como centrales, bien en dosis única, bien en perfusión continua, contribuyen a modular los estímulos nociceptivos que acceden a nivel central. La irrupción de los ultrasonidos como sistema efectivo para realizar las técnicas de anestesia regional ha permitido el desarrollo de nuevas técnicas de anestesia regional que antiguamente no podían realizarse al utilizar únicamente la neuroestimulación o las referencias cutáneas. Es fundamental tener en cuenta que aun teniendo un bloqueo efectivo es recomendable asociar otros fármacos por otras vías, de esta manera conseguiremos disminuir las dosis requeridas de forma individual e intentaremos incluso que el efecto sea sinérgico y no tan solo aditivo (AU)

Multimodal analgesia provides quality analgesia, with fewer side effects due to the use of combined analgesics or analgesic techniques. Regional anaesthesia plays a fundamental role in achieving this goal. The different techniques of regional anaesthesia that include both peripheral and central blocks in either a single dose or in continuous infusion help to modulate the nociceptive stimuli that access the central level. The emergence of the ultrasound as an effective system to perform regional anaesthesia techniques has allowed the development of new regional anaesthesia techniques that formerly could not be carried out since only neurostimulation or skin references were used (AU)

Comparative Induction of Controlled Hypotension by Electroacupuncture at DU20 Acupoint and Remifentanil in Lumbar Laminectomy.

Hypotensive anesthesia is utilized to reduce bleeding during orthopedic surgery. One of the various drugs that have been used to reduce blood pressure is remifentanil. This study was an attempt to compare the effect of remifentanil with that of electroacupuncture (EA) at DU20 on reducing blood pressure. In this randomized controlled clinical trial, 54 patients undergoing lumbar laminectomy were allocated to two groups. Hypotensive anesthesia was performed through infusion of remifentanil 100 µg/kg/min for the control group, and EA at DU20 acupoint with a frequency of 2-10 Hz and intensity of 1-5 mA for the intervention group. Blood pressure, pulse rate, volume of blood lost and the quality of surgical field were evaluated every 10 min. There were no statistically significant differences between the two groups in terms of the changes in mean arterial pressure (MAP), pulse rate, and the quality of surgical field (P > 0.05). Therefore, EA can be as effective as remifentanil to reduce blood pressure in the patients undergoing lumbar laminectomy.