State Of Sedation Research Articles

Benzodiazepine hypnotics as oral preanaesthetic medication: a comparative clinical study

Background:An ideal pre-medicant should allay fear and anxiety without producing its effect on vital functions of the body and body chemistry, with minimal depression of the respiratory and circulatory systems. The ideal pre-medicant with all good qualities and no side effects at all is yet to be found. The search for a drug which will be an appropriate pre-anesthetic medication is still going.Methods: Four drugs of BZD group namely diazepam, nitrazepam, lorazepam, and oxazepam were chosen as oral pre-anesthetic medication. Total number of cases were 100, of which 25 patients belonging to each group of drug respectively. Standard doses of oxazepam (30 mg), nitrazepam (5 mg), diazepam (10 mg) and lorazepam (2 mg) by oral route were administered. All study participants were examined night before operation to observe the following clinical parameters like level of apprehension, excitement, blood pressure, heart rate, respiration (rate, rhythm and minute volume).Results:Diazepam and nitrazepam produced fair degree of sedation whereas oxazepam appears to be lagging behind. So far as anxiolysis is concerned, all the drugs appear to be good anxiolytics. Nausea, vomiting and dizziness are some of the problems which may occasionally be faced by this group of drug. On reassessment of patients 60 minutes after premedication, it was revealed that the efficacy so as anxiolysis and sedative effect is concerned was in the following order, lorazepam headed the list; diazepam and nitrazepam followed closely and oxazepam was at the bottom. Toxicity in all the four drugs were minimal. The degree of sleepiness varied from drug to drug. Ninety minute after premedication patients were found to be in a better state of sedation than at 60 minute’s level in all the four groups. The degree of sedation and anxiolysis was in the same order as that of 60 minutes level.Conclusions:The overall impression was that four members of the benzodiazepines, serve as as a good premedication in the absence of pain. The sedation and anxioysis produced by them are of fair degree even when given orally. Side effects produced were minimal except in the lorazepam group when they are used as night time sedative. Given orally only lorazepam is capable of producing anterograde amnesia.

The application of conscious sedation with a small dose of dexmedetomidine and sufentanil in elderly patients undergoing multiple intestinal polyps resection

Objective: To explore the effectiveness and feasibility of conscious sedation with a low dose of dexmedetomidine and sufentanil during multiple intestinal polyps resection in elderly patients. Methods: Sixty elderly patients who underwent multiple intestinal polyps resection in Peking University Third Hospital from Janurary to May 2016 were randomly divided into dexmedetomidine group (D group, n=30) and propofol group (P group, n=30). There were 28 males and 32 females with a mean age of (70.4±4.5) years old (range: 65-80 years old). The patients in the dexmedetomidine group received a loading dose of 0.3 μg/kg followed by a continuous infusion of 0.2-0.4 μg·kg-1·min-1 of dexmedetomidine and sufentanil (0.1 μg/kg) respectively.The patients in the propofol group received sufentanil 0.1 μg/kg and propofol 1.5 mg/kg and followed by a continuous infusion of 3-6 mg·kg-1·h-1 of propofol.Blood pressure, heart rate, pulse oxygen saturation (SpO2), respiratory rate and bispectral index (BIS) were recorded at the basic status and at the beginning of operation, 10 min, 20 min, 30 min after operation, the end of operation and departure.The observer's assessment of alertness/sedation (OAA/S) scores and the clinical responses were also recorded.A statistical analysis was performed. Results: All patients in the two groups were sedated compared with baseline.The BIS values of patients in group D at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation were 89.6(87.8-91.0), 79.4(78.0-80.0), 76.9(75.0-80.0), 76.0(73.0-79.0) and 75.6(70.0-79.0) respectively, and those values were all significantly lower than baseline value[96.4(95.0-98.0)], (Z=-4.645, -4.788, -4.787, -4.789, -4.789, P<0.05). The OAA/S score at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation were 4.5(4.0-5.0), 3.4(3.0-4.0), 3.0(3.0-3.0), 3.5(3.0-4.0) and 3.3(3.0-4.0) respectively, and were significantly lower than baseline score [4.8(5.0-5.0)] (Z=-2.828, -4.862, -5.031, -4.420, -4.710, P<0.05). The BIS value of patients in group P at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation were 54.7(50.0-59.3), 54.8(50.0-59.3), 50.7(47.8-56.8), 54.4(51.5-58.0) and 53.7(50.0-57.3) respectively, and were significantly lower than baseline value[95.8(95.0-96.3)] (Z=-4.786, -4.787, -4.788, -4.786, -4.786, P<0.05). The OAA/S score at beginning of the operation , 10 min, 20 min, 30 min after operation and the end of operation were 0.4(0.0-1.0), 0.4(0.0-1.0), 0.4(0.0-1.0), 0.4(0.0-1.0) and 0.4(0.0-1.0) respectively, and were significantly lower than baseline score[4.9(5.0-5.0)] (Z=-4.927, -4.901, -4.912, -4.912, -4.901, P<0.05). The sedation state of group D were lighter than group P. The BIS value and OAA/S score at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation in group D were higher than group P (P<0.05). The breath and circulation were more stable in group D. The mean arterial pressure, breath rate and SpO2 at beginning of the operation, 10 min, 20 min, 30 min after operation and the end of operation in group D were higher than group P (P<0.05). There was no oxygen desaturation , hypotension and drowsiness in group D and the incidence in group P were 30.0%, 33.3% and 13.3% respectively.The emergency time and duration of stay in the PACU (post anesthesia care unit) were (2.0±1.2) and (22.0±7.4) min in group D, and they were (4.9±2.4) and (35.8±11.6) min in group P (t=-5.839, t=-5.472, P<0.05). There was no difference in surgery time, patient satisfaction and acceptance rate of reexamination (t=-3.031, t=-7.322, t=2.069, P>0.05). Conclusion: Conscious sedation with dexmedetomidine and sufentanil is effective and feasible in elderly patients undergoing multiple intestinal polyps resection.

Neural Correlates of Sevoflurane-induced Unconsciousness Identified by Simultaneous Functional Magnetic Resonance Imaging and Electroencephalography.

The neural correlates of anesthetic-induced unconsciousness have yet to be fully elucidated. Sedative and anesthetic states induced by propofol have been studied extensively, consistently revealing a decrease of frontoparietal and thalamocortical connectivity. There is, however, less understanding of the effects of halogenated ethers on functional brain networks. The authors recorded simultaneous resting-state functional magnetic resonance imaging and electroencephalography in 16 artificially ventilated volunteers during sevoflurane anesthesia at burst suppression and 3 and 2 vol% steady-state concentrations for 700 s each to assess functional connectivity changes compared to wakefulness. Electroencephalographic data were analyzed using symbolic transfer entropy (surrogate of information transfer) and permutation entropy (surrogate of cortical information processing). Functional magnetic resonance imaging data were analyzed by an independent component analysis and a region-of-interest-based analysis. Electroencephalographic analysis showed a significant reduction of anterior-to-posterior symbolic transfer entropy and global permutation entropy. At 2 vol% sevoflurane concentrations, frontal and thalamic networks identified by independent component analysis showed significantly reduced within-network connectivity. Primary sensory networks did not show a significant change. At burst suppression, all cortical networks showed significantly reduced functional connectivity. Region-of-interest-based thalamic connectivity at 2 vol% was significantly reduced to frontoparietal and posterior cingulate cortices but not to sensory areas. Sevoflurane decreased frontal and thalamocortical connectivity. The changes in blood oxygenation level dependent connectivity were consistent with reduced anterior-to-posterior directed connectivity and reduced cortical information processing. These data advance the understanding of sevoflurane-induced unconsciousness and contribute to a neural basis of electroencephalographic measures that hold promise for intraoperative anesthesia monitoring.

Distinct Cortical Signatures Associated with Sedation and Respiratory Rate Depression by Morphine in a Pediatric Population.

Opioid analgesia is an essential component of perioperative care, but effective analgesia can be limited by excessive sedation and respiratory depression. The cortical signatures associated with sedation by opioids and the relationship between changes in cortical activity and respiratory function are not well understood. The objectives of this study were to identify the electroencephalogram signatures of sedation and respiratory changes induced by morphine in a pediatric population after elective surgery. After otologic surgery, patients (14.8 ± 2.8 yr, n = 10) stayed overnight for pain relief with morphine (3 to 10 mg), hydration, and clinical observation. Electroencephalogram activity and polysomnography were performed before and after morphine, and electroencephalogram spectral properties and cardiorespiratory activities were analyzed. Compared to wakefulness and non-rapid eye movement sleep, morphine reduced high-frequency β1 (13.5 to 20 Hz) and β2 (20 to 30Hz) electroencephalogram powers (n = 10) and decreased coherence between frontal and occipital β2 electroencephalogram activities (n = 9), therefore indicating that morphine induced a deep sedative state. Morphine also reduced respiratory rate by 8.3% (n = 10). Interestingly, there was a significant correlation between the reduction in β1 electroencephalogram activity and the depression in respiratory rate induced by morphine (R = 0.715, n = 10). With significant reduction in β1 power, respiratory rate was decreased by more than 25%, suggesting that reduction in cortical arousal is associated with the severity of respiratory rate depression. Analgesic doses of morphine are associated with reduction in respiratory rate when accompanied by reduction in β1 electroencephalogram power, indicating a powerful effect of cortical arousal state per se in respiratory rate depression by morphine.

Automatic Classification of Sedation Levels in ICU Patients Using Heart Rate Variability.

To explore the potential value of heart rate variability features for automated monitoring of sedation levels in mechanically ventilated ICU patients. Multicenter, pilot study. Several ICUs at Massachusetts General Hospital, Boston, MA. Electrocardiogram recordings from 40 mechanically ventilated adult patients receiving sedatives in an ICU setting were used to develop and test the proposed automated system. Richmond Agitation-Sedation Scale scores were acquired prospectively to assess patient sedation levels and were used as ground truth. Richmond Agitation-Sedation Scale scores were grouped into four levels, denoted "unarousable" (Richmond Agitation- Sedation Scale = -5, -4), "sedated" (-3, -2, -1), "awake" (0), "agitated" (+1, +2, +3, +4). A multiclass support vector machine algorithm was used for classification. Classifier training and performance evaluations were carried out using leave-oneout cross validation. An overall accuracy of 69% was achieved for discriminating between the four levels of sedation. The proposed system was able to reliably discriminate (accuracy = 79%) between sedated (Richmond Agitation-Sedation Scale < 0) and nonsedated states (Richmond Agitation-Sedation Scale > 0). With further refinement, the methodology reported herein could lead to a fully automated system for depth of sedation monitoring. By enabling monitoring to be continuous, such technology may help clinical staff to monitor sedation levels more effectively and to reduce complications related to over- and undersedation.

Suicide kit purchased on the Internet: A case report of self-poisoning with pentobarbital

Popularization of assisted-suicide and increase of online drug sellers could lead to resurgence of self-poisoning by a forgotten drug: pentobarbital. We report a case of self-poisoning with pentobarbital purchased on a Chinese website. A 43-year old woman with a background history of borderline personality disorder ingested at home a “suicide kit” (pentobarbital sodium) purchased beforehand on the Internet, a few minutes before calling the French national emergency telephone number. Upon admission, she was comatose, Glasgow Coma Score (GCS) 3/15, symmetrical slight myosis, generalized hypotonia and hyporeflexia. Blood pressure was 96/66 mmHg, heart rate was 93/min, and body temperature was 33.3 °C. Blood gas analysis showed a metabolic acidosis and severe hypoxemia, related to an aspiration pneumonia (arterial pH 7.30, pCO 2 40.7 mmHg, pO 2 63.3 mmHg with F i O 2 = 1). Hemodynamic instability rapidly appeared and norepinephrine infusion was started (up to 0.32 μg/kg/min). At day 2, clinical examination revealed signs consistent with brain death, i.e. bilateral mydriasis with absence of pupillary and oculo-cardiac reflexes. Electroencephalographic study found a severe diffuse slowing compatible with a sedative state. Plasma pentobarbital concentration was 19.9 μg/mL. At day 3, brain-stem reflexes reappeared, although pentobarbital concentration was still beyond lethal range, at 18.1 μg/mL. Neurological evolution was then progressively favourable. GCS was 5/15 at day 5, corresponding to a concentration of 9.4 μg/mL, and 15/15 at day 6 allowing extubation of the patient. She was finally discharged to the psychiatry department at day 10. Pentobarbital is a short-acting barbiturate, now rarely used in suicide attempt because it is no longer prescribed for medical purposes in most countries. Only a few cases have been published in the last decade, mostly among veterinarians because this drug is used as euthanasia agent. Pentobarbital is indeed the drug of choice for assisted-suicide. Pentobarbital is a weak acid with high lipid-solubility. After oral absorption, it is readily absorbed with an onset of action of 10 to 60 minutes. The degree of protein binding is about 45 to 70% and the volume of distribution is 0.5 to 1L/Kg. The plasma half-life for pentobarbital is 15 to 50 hours and appears to be dose-dependent. Renal excretion is negligible (< 1%). Pentobarbital is metabolized by the liver and excreted in the urine as inactive metabolites. Consciousness impairment, respiratory and circulatory depression are the main effects of acute poisoning. At worst, severe poisoning can mimic clinical and EEG features of brain death. Therapeutic blood levels are 1–3 μg/mL; levels are considered toxic at 5 μg/mL or more and reported lethal blood concentrations range from 10 to 169 μg/mL. Management of pentobarbital poisoning is mainly based on supportive care. Invasive mechanical ventilation, fluid loading and vasopressors are required in most severe cases. Several procedures to enhance elimination have been reported. Forced diuresis with urinary alkalinisation is not effective for short-acting barbiturates. Hemodialysis, hemoperfusion or continuous venovenous hemodiafiltration have been proposed as therapeutic options but improvement in supportive therapies make these techniques obsolete. Pentobarbital is readily available without prescription on the Internet. Although there is little public awareness about this drug, current mediatisation of assisted-suicide could lead to an increased interest from suicide attempters. Supportive care is the cornerstone of medical management.

Alfaxalone Anaesthesia Facilitates Electrophysiological Recordings of Nociceptive Withdrawal Reflexes in Dogs (Canis familiaris).

Naturally occurring canine osteoarthritis represents a welfare issue for affected dogs (Canis familiaris), but is also considered very similar to human osteoarthritis and has therefore been proposed as a model of disease in humans. Central sensitisation is recognized in human osteoarthritis sufferers but identification in dogs is challenging. Electromyographic measurement of responses to nociceptive stimulation represents a potential means of investigating alterations in central nociceptive processing, and has been evaluated in conscious experimental dogs, but is likely to be aversive. Development of a suitable anaesthetic protocol in experimental dogs, which facilitated electrophysiological nociceptive withdrawal reflex assessment, may increase the acceptability of using the technique in owned dogs with naturally occurring osteoarthritis. Seven purpose bred male hound dogs underwent electromyographic recording sessions in each of three states: acepromazine sedation, alfaxalone sedation, and alfaxalone anaesthesia. Electromyographic responses to escalating mechanical and electrical, and repeated electrical, stimuli were recorded. Subsequently the integral of both early and late rectified responses was calculated. Natural logarithms of the integral values were analysed within and between the three states using multi level modeling. Alfaxalone increased nociceptive thresholds and decreased the magnitude of recorded responses, but characteristics of increasing responses with increasing stimulus magnitude were preserved. Behavioural signs of anxiety were noted in two out of seven dogs during recordings in the acepromazine sedated state. There were few significant differences in response magnitude or nociceptive threshold between the two alfaxalone states. Following acepromazine premedication, induction of anaesthesia with 1–2 mg kg-1 alfaxalone, followed by a continuous rate infusion in the range 0.075–0.1 mg kg-1 min-1 produced suitable conditions to enable assessment of spinal nociceptive processing in dogs, without subjecting them to potentially aversive experiences. This methodology may be appropriate for obtaining electrophysiological nociceptive withdrawal reflex data in client-owned dogs with naturally occurring osteoarthritis.

Optimum anesthesia for reliable urethral pressure profilometry in female dogs and goats.

To investigate the effects of propofol and isoflurane on urethral pressure profilometry of female dogs and goats, and to identify the method of anesthesia that least influences urethral pressure profilometry and to assess its reproducibility. The effects of premedication with midazolam, propofol sedation and isoflurane anesthesia were assessed in five female dogs. The effects of propofol and isoflurane were compared in seven goats, whereas in another group of 19 goats, the state of deep propofol sedation was compared with the state of recovery from propofol sedation. The coefficient of reproducibility and within-subject coefficient of variation were calculated to evaluate test-retest reproducibility. In conscious female dogs, maximal urethral closure pressure and functional area were significantly higher than under propofol or isoflurane (P = 0.04), but not different from the recovery state. In six of seven goats, maximal urethral closure pressure and functional area were higher when measured under propofol sedation than under isoflurane (median maximal urethral closure pressure, 69 vs 47 cmH2 O; P = 0.03). Maximal urethral closure pressure was lower under propofol than during recovery from propofol in 17 of 19 goats (median maximal urethral closure pressure, 54 vs 66 cmH2 O; P < 0.001). The test-retest coefficient of reproducibility for goats was 28 cmH2 O, and the within-subject coefficient of variation was 16%. In dogs, urethral pressure profilometry should be measured in conscious animals whenever possible. In goats, urethral pressure profilometry is least affected during recovery from propofol sedation, and it shows acceptable reproducibility under this condition.

Changes in First Postoperative Night Bispectral Index After Daytime Sedation Induced by Dexmedetomidine or Midazolam Under Regional Anesthesia: A Randomized Controlled Trial

Background and ObjectivesSupplementation of spinal anesthesia with various sedatives is a standard protocol to alleviate patient anxiety associated with the surgical procedure. We hypothesized that, compared with dexmedetomidine, midazolam might...

In response to the editorial "Sedation in endoscopy in 2016: Is it safe sedation with propofol led by the endoscopist in complex situations?"

It is universally accepted that deep sedation involves more risks than light-to-moderate sedation. Deep sedation for endoscopic explorations is normally provided by anesthesiologists in Spain and in most countries of the European Unión. The present debate about deep sedation-anesthesia states goes beyond the topic of cardiovascular and respiratory adverse events, and targets the cognitive consequences and global increased mortality of uncontrolled sedation states, especially in specific fragile populations. We consider that strong recomendations for sedative techniques in endoscopic procedures should be made in Spain taking in consideration to two basic principles: 1) according to published evidence concerning patient safety, deep sedation must be an unequivocal responsibility of the anesthesiologist, and 2) we must define which patients are candidates for deep sedation during endoscopic procedures, as this will help to regulate patient flow in clinics and to reduce adverse effects associated with overtreatment of patients.

The Algoplus Score to Assess Acute Postoperative pain in Elderly patients–A Pilot Observational Study

Standard verbal or analogue scales may not be accurate to assess acute postoperative pain in elderly patients. This study was designed to field test the Algoplus tool, developed specifically for this population and based on observation of patient behavior. Prospective, observational cohort. Single center, French University hospital. Forty-eight patients, aged over 65, scheduled for surgery under general anesthesia, and observed on admission to the postanesthesia care unit, immediately after extubation, during the different steps of analgesic intervention (demand, relief with intravenous opioid titration, plus intermediate measures when relevant), and either at discharge or 3 hours after admission. A numerical rating scale (NRS) was used to guide analgesia. The Algoplus score and the state of alertness or sedation were noted. NRS scores and Algoplus scores were significantly related, and both scores significantly decreased under the effect of analgesia, but the correlation was low. In early observations, the Algoplus score was higher than that predicted by the NRS score, in relation to residual sedation. Female gender tended to lower the Algoplus score compared to the NRS score. When the NRS score exceeded 3/10, indicating the need for analgesic intervention, the Algoplus score was generally lower than the recommended trigger for analgesia (2/5). These results are promising, but further evidence of a clinical benefit to the use of Algoplus for acute postoperative pain is needed. In future studies, scoring should be adjusted to take into account the time from extubation, the state of sedation, and the patient's gender in order to interpret results.

Variation of the default mode network with altered alertness levels induced by propofol.

BackgroundThe default mode network (DMN) is closely associated with the maintenance of alertness and cognitive functions. This study aimed to observe the changes in DMN induced by increasing doses of propofol and progressively deepening sedation.MethodsTwelve healthy subjects were selected; they received target-controlled infusion of propofol (1.0 and 3.0 μg/mL of plasma) and underwent functional magnetic resonance imaging before sedation and when they achieved light and deep sedation states. The average degree, average shortest path length, global efficiency, local efficiency, and clustering coefficient of DMN were assessed to study the overall and internal changes of DMN with gradual changes in alertness level, as well as the relationship between thalamus and DMN. Meanwhile, basic vital signs and respiratory inhibition were recorded.ResultsDMN parameters were gradually inhibited with decreasing level of alertness, the differences were significant between light sedation and awake states (all P<0.01), but not between deep and light sedation states. However, the shortest path lengths of the posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortexes in the DMN were significantly increased under deep sedation.ConclusionOverall, DMN is propofol-sensitive. A small dose of propofol can significantly inhibit the DMN, affecting the level of alertness. The posterior cingulate cortex, medial prefrontal cortex, and lateral parietal cortexes in the DMN are less sensitive to propofol, and could be significantly inhibited by a higher concentration of propofol, further reducing the level of alertness.

Enhancing a sedation score to include truly noxious stimulation: the Extended Observer's Assessment of Alertness and Sedation (EOAA/S)

Although the Modified Observer's Assessment of Alertness and Sedation (MOAA/S) is frequently used in sedation-related drug and device studies, a major shortcoming is that it does not differentiate between lighter and deeper levels of general anaesthesia because the only noxious stimulus of the MOAA/S is a trapezius squeeze. The primary aim of this investigation was to expand the MOAA/S score to include truly noxious stimulation, thereby extending the dynamic range of the assessment to include sedation states consistent with deeper levels of general anaesthesia. Twenty healthy volunteers received target controlled infusions of fentanyl (target=0.8 ng ml(-1)) and propofol (starting at 0.5 µg ml(-1) and gradually increasing to 5 µg ml(-1)). At each propofol concentration, a MOAA/S score was obtained before and after tetanic electrical stimulation. The tetanic electrical stimulation current was gradually increased until the subject responded or until 50 mA was delivered without a response. A pharmacodynamic model was constructed to characterize the concentration-effect relationship between propofol and the MOAA/S scores. All subjects required a significantly higher propofol concentration to produce unresponsiveness to tetanic electrical stimulation at 50 mA compared with a standardized trapezius squeeze. The pharmacodynamic model adequately characterized the concentration-effect relationship. The Extended Observer's Assessment of Alertness and Sedation (or EOAA/S) extends the range of the widely used MOAA/S score to include truly noxious stimulation, thereby enabling the identification of drug-induced central nervous system depression representative of surgical anaesthesia.

Sedation and analgesia with fentanyl and etomidate for intrathecal injection in childhood leukemia patients.

In this study, we tried to find a safe as well as fast effective treatment for sedation and analgesia for intrathecal injection in childhood leukemia patients, relieving treatment difficulties and pain, increasing the success rate of single intrathecal injection.The patients were divided into the experimental group (fentanyl combined with etomidate) and the control group (lidocaine only) randomly. The experimental group was given fentanyl 1 to 2 μg/kg intravenously first, then etomidate 0.1 to 0.3 mg/kg intravenously after the pipe washed. The patients younger than 1.5 years or who did not achieve satisfied sedative and analgesic situation received an additional time of etomidate (0.1-0.3 mg/kg). The patients were given oxygen at the rate of 4-5 L/min during the whole operation, and the finger pulse oximeter was used simultaneously to detect the changes in heart rate (HR) and blood oxygen saturation (SpO2). The doctors who performed the procedures assessed the quality of sedation and analgesia.In the experimental group, the patients' HR increased slightly after given fentanyl combined with etomidate. The patients' SpO2 was stable. Most patients achieved a good sedative and analgesic state within 1 to 2 minutes, and no case of respiration depression or cardiac arrhythmias occurred during the whole operation. The wake-up time was 55.42 ± 20.62 min. In the control group, the patients were not very cooperative during the intrathecal injection, which made the procedures very difficult.During intrathecal injection, pain obviously reduced and the success rate of single lumbar puncture increased. It is safe and effective to apply fentanyl combined with etomidate for sedation and analgesia.

Quality indicators common to all GI endoscopic procedures.

Quality of care is the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge (1). The American Society for Gastrointestinal Endoscopy (ASGE), the American College of Gastroenterology (ACG), and the American Gastroenterological Association (AGA) have continually promoted the ideal that all patients have access to high-quality GI endoscopy services. A high-quality endoscopy is an examination in which patients receive an indicated procedure, correct and relevant diagnoses are recognized or excluded, any therapy provided is appropriate, and all steps that minimize risk have been taken.

The G protein-biased κ-opioid receptor agonist RB-64 is analgesic with a unique spectrum of activities in vivo.

The hypothesis that functionally selective G protein-coupled receptor (GPCR) agonists may have enhanced therapeutic benefits has revitalized interest for many GPCR targets. In particular, although κ-opioid receptor (KOR) agonists are analgesic with a low risk of dependence and abuse, their use is limited by a propensity to induce sedation, motor incoordination, hallucinations, and dysphoria-like states. Several laboratories have produced a body of work suggesting that G protein-biased KOR agonists might be analgesic with fewer side effects. Although that has been an intriguing hypothesis, suitable KOR-selective and G protein-biased agonists have not been available to test this idea. Here we provide data using a G protein-biased agonist, RB-64 (22-thiocyanatosalvinorin A), which suggests that KOR-mediated G protein signaling induces analgesia and aversion, whereas β-arrestin-2 signaling may be associated with motor incoordination. Additionally, unlike unbiased KOR agonists, the G protein-biased ligand RB-64 does not induce sedation and does not have anhedonia-like actions, suggesting that a mechanism other than G protein signaling mediates these effects. Our findings provide the first evidence for a highly selective and G protein-biased tool compound for which many, but not all, of the negative side effects of KOR agonists can be minimized by creating G protein-biased KOR agonists.

P065: Correlation between anticholinergic and sedative drug burden and Mini-Mental State Examination

P065: Correlation between anticholinergic and sedative drug burden and Mini-Mental State Examination

Algorithm for Quantifying Frontal EMG Responsiveness for Sedation Monitoring.

To study stimulation-related facial electromyographic (FEMG) activity in intensive care unit (ICU) patients, develop an algorithm for quantifying the FEMG activity, and to optimize the algorithm for monitoring the sedation state of ICU patients. First, the characteristics of FEMG response patterns related to vocal stimulation of 17 ICU patients were studied. Second, we collected continuous FEMG data from 30 ICU patients. Based on these data, we developed the Responsiveness Index (RI) algorithm that quantifies FEMG responses. Third, we compared the RI values with clinical sedation level assessments and adjusted algorithm parameters for best performance. In patients who produced a clinically observed response to the vocal stimulus, the poststimulus FEMG power was 0.33 µV higher than the prestimulus power. In nonresponding patients, there was no difference. The sensitivity and specificity of the developed RI for detecting deep sedation in the subgroup with low probability of encephalopathy were 0.90 and 0.79, respectively. Consistent FEMG patterns were found related to standard stimulation of ICU patients. A simple and robust algorithm was developed and good correlation with clinical sedation scores achieved in the development data.

Capnography monitoring in procedural sedation for bronchoscopy.

Capnography monitoring in procedural sedation for bronchoscopy.

Hemodynamic response to fluid management in children undergoing dexmedetomidine sedation for MRI.

Dexmedetomidine is administered for pediatric sedation for MRI studies. It has the advantage of preserving respiratory function and producing a sedation state identical to that of natural sleep. It can, however, cause a dose-dependent decrease in systemic blood pressure in children. The purpose of this study was to investigate whether i.v. fluid loading with normal saline solution before the initiation of dexmedetomidine administration would affect the frequency of hypotension. Quality assurance data on consecutively registered children who were sedated with dexmedetomidine for MRI were reviewed. All children received a bolus of 3 μg/kg dexmedetomidine followed by a continuous infusion of 2 mg/ kg/h. A normal saline fluid bolus consisting of 0, 10, or 20 mL/kg was administered to each child within 1 hour before initiation of dexmedetomidine administration. Hypotension was defined as a greater than 20% decrease in mean arterial blood pressure from baseline. Sedation was administered to 1692 children. Data on fluid administration were missing in three cases. In the other cases, 252 (14.9%) children received 0 mL/kg of normal saline solution, 598 (35.3%) received 10 mL/kg, and 839 (49.6%) received 20 mL/kg. In a multiple logistic regression model controlled for confounding variables, the odds of development of hypotension with 10 mL/kg of fluid decreased 53% (odds ratio, 0.47; 95% CI, 0.28-0.79; p = 0.004) compared with 0 mL/kg. Administration of 10 mL/kg of normal saline solution before the initiation of dexmedetomidine administration for pediatric MRI sedation is effective in decreasing the incidence of observed hypotension.