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To evaluate cardiopulmonary, arterial blood gas and propofol-sparing effects of magnesium sulfate (MgSO 4) constant rate infusion (CRI) in mechanically ventilated dogs maintained under total intravenous anesthesia with propofol. Blinded, randomized, clinical trial. A total of 24 healthy adult dogs. Dogs were premedicated with intramuscular acepromazine (0.05 mg kg–1) and morphine (0.5 mg kg–1), followed by an intravenous (IV) bolus of saline or MgSO 4 (50 mg kg–1 over 15 minutes) and propofol (given to effect to induce anesthesia). Anesthesia was maintained with an IV propofol infusion (beginning at 0.3 mg kg–1 minute–1, adjusted as necessary). Concurrently, one of three IV infusions were administered: GS (0.9% NaCl), GM30 (MgSO 4 , 30 mg kg–1 hour–1) or GM80 (MgSO 4 , 80 mg kg–1 hour–1). Propofol induction and maintenance doses were recorded. The following variables were recorded at baseline (T0), after bolus treatment (T1), after beginning mechanical ventilation (T5) and every 15 minutes until the end of the procedure (T15–T120): mean arterial pressure, heart rate, peripheral oxygen saturation, end-tidal partial pressure of CO 2 , temperature, blood gas variables, indirect calorimetry and extubation time. Values of p < 0.05 were considered significant. Propofol induction bolus dose was lower in GM30 (31.2%, p = 0.04) and GM80 (38.9%, p = 0.003) than in GS. The maintenance propofol infusion rate in GM80 was 16.9% lower (p = 0.03), resulting in fewer propofol CRI rescues during the perioperative period. GM30 and GM80 exhibited faster extubation times than GS (46.2%, p = 0.002 and 48.9%, p = 0.001, respectively). Infusion of a 50 mg kg–1 bolus, followed by CRI of MgSO 4 (30 and 80 mg kg–1 hour–1), reduces the propofol induction and maintenance (CRI) requirement, maintaining cardiorespiratory stability and reducing the time required to extubation. [ABSTRACT FROM AUTHOR]

Airway management including endotracheal intubation (ETI) is a key skill for emergency clinicians. Therefore, it is important for emergency clinicians to be aware of the current evidence regarding the identification and management of patients requiring ETI. This paper evaluates key evidence-based updates concerning ETI for the emergency clinician. ETI is commonly performed in the emergency department (ED) setting but has many nuanced components. There are several tools that have been used to predict a difficult airway which incorporate anatomic and physiologic features. While helpful, these tools should not be used in isolation. Preoxygenation and apneic oxygenation are recommended to reduce the risk of desaturation and patient decompensation, particularly with noninvasive ventilation in critically ill patients. Induction and neuromuscular blocking medications should be tailored to the clinical scenario. Video laryngoscopy is superior to direct laryngoscopy among novice users, while both techniques are reasonable among more experienced clinicians. Recent literature suggests using a bougie during the first attempt. Point-of-care ultrasound is helpful for confirming correct placement and depth of the endotracheal tube. An understanding of literature updates can improve the ED care of patients requiring emergent intubation. [ABSTRACT FROM AUTHOR]

Mechanical ventilation is a common invasive intervention in intensive care units. While respiratory failure remains the most common indication for mechanical ventilation, the application and indications of this intervention are far more variable. Ventilation causes marked alteration to human physiology and is associated with complications and iatrogenic injuries. This article highlights practical aspects of patient management during invasive ventilation. [ABSTRACT FROM AUTHOR]

Sedation is used widely on critical care and is necessary to facilitate and alleviate the stress of invasive and potentially painful organ supportive therapies. Its use, however, is associated with morbidity and mortality. Treatments therefore need to be minimized and optimized wherever possible with overtreatment being avoided. It should be patient centred, with a focus of treating pain and agitation and delirium, common symptoms in critical care. Delirium itself is associated with morbidity and mortality and as such, all healthcare professionals involved with the care of the critically ill have a duty to identify, manage and minimize this distressing complication. [ABSTRACT FROM AUTHOR]

To compare the effects of intranasal (IN) and intramuscular (IM) midazolam–butorphanol–ketamine on intraocular pressure (IOP), tear production (TP) and sedation in rabbits. Prospective, randomized, crossover experimental study. Fourteen male New Zealand White rabbits, aged 1–2 years, body mass 3.1 ± 0.8 kg (mean ± standard deviation). Rabbits were administered midazolam (1 mg kg–1), butorphanol (1.5 mg kg–1) and ketamine (5 mg kg–1) via IN and IM routes. IOP, TP and sedation scores were assessed at 0 (before drug administration), 5, 15, 30, 45 and 60 minutes after drug administration. Heart rate (HR), respiratory rate (f R), rectal temperature (RT), noninvasive mean arterial blood pressure (MAP) and peripheral hemoglobin oxygen saturation (SpO 2) were simultaneously recorded until 45 minutes after drug administration. The onset and duration of sedation and sedation scores were recorded. Drug delivery route had no significant impact on mean IOP (p = 0.271) or TP (p = 0.062), and there were no significant changes over time for IOP (p = 0.711) or TP (p = 0.372). Similarly, delivery route had no significant impact on HR (p = 0.747), f R (p = 0.872), RT (p = 0.379), MAP (p = 0.217) and SpO 2 (p = 0.254). Sedation onset was faster with IN (3.0 ± 1.0 minutes) than with IM administration (4.9 ± 0.7 minutes) (p = 0.011), but sedation duration was significantly longer with IM (52.6 ± 7.2 minutes) than with IN delivery (30.7 ± 6.8 minutes) (p = 0.004). There was no significant difference in sedation scores between the two delivery routes at any of the recorded time points. The combination of midazolam–butorphanol–ketamine had minimal impact on physiological and ocular variables regardless of the route of administration, whereas IN drug administration led to a shorter onset and duration of action than IM administration. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the clinical application of delayed repeated air enema (DRE) with sedation in pediatric intussusception. We retrospectively assessed cases of idiopathic intussusception treated with air enema reduction at the emergency department of Beijing Children's Hospital affiliated to Capital Medical University from January 2016 to August 2019. The included cases were assigned to the success or failure groups based on the outcomes of DRE with sedation. General patient information, clinical manifestations, test results, and surgical conditions were collected for comparative analysis. A total of 3052 cases were initially diagnosed with intussusception and underwent air enema reduction. Ultimately, 211 cases were included, with 162 in the success group and 49 in the failure group. The success rate of DRE with sedation was 76.8% (162/211), with an overall reduction success rate of 97.8% (2984/3052). Univariate logistic regression analysis showed that patients in the failure group had a significantly higher proportion of patients with age ≤1 year, bloody stools, and left-sided intussusception before DRE compared to the success group (OR = 2.3, 95%CI: 1.1∼4.6, P = 0.023; OR = 3.4, 95%CI: 1.6∼7.2, P = 0.002 and OR = 12.6, 95%CI: 4.6∼34.6, P < 0.001). Multiple logistic regression analysis based on these three factors revealed that the risk of DRE failure was 10.1 times higher in cases with the left-sided intussusception before DRE. DRE with sedation can improve the overall enema reduction success rate for intussusception and has good feasibility and safety profiles. Left-sided intussusception before DRE is an independent risk factor for enema failure. [ABSTRACT FROM AUTHOR]

• 14.5 % of the moderate-to-severe traumatic brain injury patients were exposed to early dexmedetomidine. • There was no significant association between early dexmedetomidine exposure and day 3 biomarkers. • Dexmedetomidine might be a safe choice for ICU sedation. Traumatic brain injury (TBI) triggers autonomic dysfunction and inflammatory response that can result in secondary brain injuries. Dexmedetomidine is an alpha-2 agonist that may modulate autonomic function and inflammation and has been increasingly used as a sedative agent for critically ill TBI patients. We aimed to investigate the association between early dexmedetomidine exposure and blood-based biomarker levels in moderate-to-severe TBI (msTBI). We conducted a retrospective cohort study using data from the Transforming Clinical Research and Knowledge in Traumatic Brain Injury Study (TRACK-TBI), which enrolled acute TBI patients prospectively across 18 United States Level 1 trauma centers between 2014–2018. Our study population focused on adults with msTBI defined by Glasgow Coma Scale score 3–12 after resuscitation, who required mechanical ventilation and sedation within the first 48 h of ICU admission. The study's exposure was early dexmedetomidine utilization (within the first 48 h of admission). Primary outcome included brain injury biomarker levels measured from circulating blood on day 3 following injury, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), neuron-specific enolase (NSE), S100 calcium-binding protein B (S100B) and the inflammatory biomarker C-reactive protein (CRP). Secondary outcomes assessed biomarker levels on days 5 and 14. Linear mixed-effects regression modelling of the log-transformed response variable was used to analyze the association of early dexmedetomidine exposure with brain injury biomarker levels. Among the 352 TRACK-TBI subjects that met inclusion criteria, 50 (14.2 %) were exposed to early dexmedetomidine, predominantly male (78 %), white (81 %), and non-Hispanic (81 %), with mean age of 39.8 years. Motor vehicle collisions (27 %) and falls (22 %) were common causes of injury. No significant associations were found between early dexmedetomidine exposure with day 3 brain injury biomarker levels (GFAP, ratio = 1.46, 95 % confidence interval [0.90, 2.34], P = 0.12; UCH-L1; ratio = 1.17 [0.89, 1.53], P = 0.26; NSE, ratio = 1.19 [0.92, 1.53], P = 0.19; S100B, ratio = 1.01 [0.95, 1.06], P = 0.82; hs-CRP, ratio = 1.29 [0.91, 1.83], P = 0.15). The hs-CRP level at day 14 in the dexmedetomidine group was higher than that of the non-exposure group (ratio = 1.62 [1.12, 2.35], P = 0.012). There were no significant associations between early dexmedetomidine exposure and day 3 brain injury biomarkers in msTBI. Our findings suggest that early dexmedetomidine use is not correlated with either decrease or increase in brain injury biomarkers following msTBI. Further research is necessary to confirm these findings. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the echocardiographic effects of intravenous medetomidine and vatinoxan in dogs with stage B1 mitral valve disease. We hypothesised medetomidine-vatinoxan would reduce the need for manual restraint during echocardiography without producing detrimental cardiovascular effects or echocardiographic changes. Twelve client-owned dogs with stage B1 mitral valve disease. A transthoracic echocardiographic examination was performed before and after sedation with intravenous medetomidine (10 μg/kg) and vatinoxan (200 μg/kg). Vital parameters were also recorded, and the level of sedation was assessed subjectively. The data were analysed with Student's t -tests with an alpha level of <0.05. End-systolic volume and left ventricular systolic diameter increased (from 0.89 ± 0.19 mL/kg to 1.13 ± 0.29 mL/kg and 0.96 ± 0.12 cm to 1.10 ± 0.10 cm, respectively) and ejection fraction (from 66.33 ± 4.0% to 56.23 ± 9.54%) and fractional shortening (from 36.13 ± 5.42% to 27.24 ± 5.6%) decreased significantly after sedation. End diastolic volume, left ventricular diastolic diameter, and left atrial size remained statistically unchanged, while aortic (from 1.34 ± 0.2 m/s to 0.99 ± 0.14 m/s) and pulmonic (from 0.94 ± 0.16 m/s to 0.66 ± 0.15 m/s) velocities decreased significantly. No dogs had a mean arterial pressure below 65 mmHg. Sedation enabled echocardiographic examination without manual restraint. No adverse effects were observed with the dose studied. Echocardiographic parameters were not completely comparable with the baseline values, which should be taken into consideration when evaluating dogs sedated with intravenous medetomidine-vatinoxan. [ABSTRACT FROM AUTHOR]

Patients exhibiting signs of hyperactive delirium with severe agitation (HDSA) may require sedating medications for stabilization and safe transport to the hospital. Determining the patient's weight and calculating the correct weight-based dose may be challenging in an emergency. A fixed dose ketamine protocol is an alternative to the traditional weight-based administration, which may also reduce dosing errors. The objective of this study was to evaluate the frequency and characteristics of adverse events following pre-hospital ketamine administration for HDSA. Emergency Medical Services (EMS) records from four agencies were searched for prehospital ketamine administration. Cases were included if a 250 mg dose of ketamine was administered on standing order to an adult patient for clinical signs consistent with HDSA. Protocols allowed for a second 250 mg dose of ketamine if the first dose was not effective. Both the 250 mg initial dose and the total prehospital dose were analyzed for weight based dosing and adverse events. Review of 132 cases revealed 60 cases that met inclusion criteria. Patients' median weight was 80 kg (range: 50-176 kg). No patients were intubated by EMS, one only requiring suction, three required respiratory support via bag valve mask (BVM). Six (10%) patients were intubated in the emergency department (ED) including the three (5%) supported by EMS via BVM, three (5%) others who were sedated further in the ED prior to requiring intubation. All six patients who were intubated were discharged from the hospital with a Cerebral Performance Category (CPC) 1 score. The weight-based dosing equivalent for the 250 mg initial dose (OR: 2.62, CI: 0.67–10.22) and the total prehospital dose, inclusive of the 12 patients that were administered a second dose, (OR: 0.74, CI: 0.27, 2.03), were not associated with the need for intubation. The 250 mg fixed dose of ketamine was not >5 mg/kg weight-based dose equivalent for all patients in this study. Although a second 250 mg dose of ketamine was permitted under standing orders, only 12 (20%) of the patients were administered a second dose, none experienced an adverse event. This indicates that the 250 mg initial dose was effective for 80% of the patients. Four patients with prehospital adverse events likely related to the administration of ketamine were found. One required suction, three (5%) requiring BVM respiratory support by EMS were subsequently intubated upon arrival in the ED. All 60 patients were discharged from the hospital alive. Further research is needed to determine an optimal single administration dose for ketamine in patients exhibiting signs of HDSA, if employing a standardized fixed dose medication protocol streamlines administration, and if the fixed dose medication reduces the occurrence of dosage errors. [ABSTRACT FROM AUTHOR]

Sleep disruption is a common occurrence during medical care and is detrimental to patient recovery. Long-term sedation in the critical care setting is a modifiable factor that affects sleep, but the impact of different sedative–hypnotics on sleep homeostasis is not clear. We conducted a systematic comparison of the effects of prolonged sedation (8 h) with i.v. and inhalational agents on sleep homeostasis. Adult Sprague–Dawley rats (n =10) received dexmedetomidine or midazolam on separate days. Another group (n =9) received propofol or sevoflurane on separate days. A third group (n =12) received coadministration of dexmedetomidine and sevoflurane. Wakefulness (wake), slow-wave sleep (SWS), and rapid eye movement (REM) sleep were quantified during the 48-h post-sedation period, during which we also assessed wake-associated neural dynamics using two electroencephalographic measures: theta-high gamma phase-amplitude coupling and high gamma weighted phase-lag index. Dexmedetomidine-, midazolam-, or propofol-induced sedation increased wake and decreased SWS and REM sleep (P <0.0001) during the 48-h post-sedation period. Sevoflurane produced no change in SWS, decreased wake for 3 h, and increased REM sleep for 6 h (P <0.02) post-sedation. Coadministration of dexmedetomidine and sevoflurane induced no change in wake (P >0.05), increased SWS for 3 h, and decreased REM sleep for 9 h (P <0.02) post-sedation. Dexmedetomidine, midazolam, and coadministration of dexmedetomidine with sevoflurane reduced wake-associated phase-amplitude coupling (P ≤0.01). All sedatives except sevoflurane decreased wake-associated high gamma weighted phase-lag index (P <0.01). In contrast to i.v. drugs, prolonged sevoflurane sedation produced minimal changes in sleep homeostasis and neural dynamics. Further studies are warranted to assess inhalational agents for long-term sedation and sleep homeostasis. [ABSTRACT FROM AUTHOR]

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Quantitative measurement of pupil change has not been assessed against the Richmond Agitation and Sedation Scale (RASS) and spectral edge frequency (SEF) during sedation. The aim of this study was to evaluate pupillometry against these measures in sedated critically ill adult patients. In ventilated and sedated patients, pupillary variables were measured by automated pupillometry at each RASS level from −5 to 0 after discontinuation of hypnotics, while processed electroencephalogram variables were displayed continuously and SEF was recorded at each RASS level. Correlations were made between percentage pupillary light reflex (%PLR) and RASS, and between %PLR and SEF. The ability of %PLR to differentiate light sedation (RASS ≥−2), moderate (RASS =−3), and deep sedation (RASS ≤−4) was assessed by areas under receiver operating characteristic (ROC) curves. A total of 163 paired measurements were recorded in 38 patients. With decreasing sedation depth, median %PLR increased progressively from 20% (interquartile range 17–25%) to 36% (interquartile range 33–40%) (P <0.001). Strong correlations were found between %PLR and RASS (Rho=0.635) and between %PLR and SEF (R=0.641). Area under the curve (AUC) of 0.87 with a %PLR threshold of 28% differentiated moderate/light sedation from deep sedation with sensitivity of 83% and specificity of 83%. An AUC of 0.82 with a threshold of 31% distinguished light sedation from moderate/deep sedation with a sensitivity of 81% and a specificity of 75%. Quantitative assessment of %PLR correlates with other indicators of sedation depth in critically ill patients. [ABSTRACT FROM AUTHOR]

The article focuses on the use of volatile anaesthetics for sedation in intensive care units, with a particular emphasis on their efficacy and safety. Topics discussed include the comparison of volatile anaesthetics with other sedation methods, their impact on patient outcomes, and the current understanding of their mechanisms of action and pharmacokinetics.

Delayed emergence from general anaesthesia, opioid-induced sedation, and opioid-induced respiratory depression is associated with perioperative complications. We characterised the preclinical effects of the orexin receptor 2 (OX2R)-selective agonist danavorexton (TAK-925) on emergence from anaesthesia and reversal of fentanyl-induced sedation, respiratory depression, and analgesia. Emergence from isoflurane- or propofol-induced anaesthesia and fentanyl-induced sedation were investigated by righting reflex, rotarod, and electroencephalography in rats or monkeys. Fentanyl-induced respiratory depression was assessed by arterial blood gas analysis and whole-body plethysmography in rats and monkeys. Analgesia was evaluated using formalin- and skin incision-induced pain models in rats. Danavorexton shortened emergence from isoflurane- or propofol-induced anaesthesia and from fentanyl-induced sedation at 1 (P =0.005), 3 (P =0.006), and 3 mg kg−1 s.c. (P =0.022), respectively, by righting reflex in rats. Danavorexton (10 mg kg−1 s.c.) accelerated recovery from isoflurane-, propofol- and fentanyl-induced motor impairment in separate rotarod tests in rats (P =0.008, P =0.007, P =0.017, respectively), and reversed anaesthesia and fentanyl-induced delta-power increases. Danavorexton shortened emergence (return of righting reflex) from isoflurane- or propofol-induced anaesthesia at 1 (P =0.002) and 3 mg kg−1 (P =0.004), respectively, in cynomolgus monkeys. Danavorexton (10 mg kg−1 s.c.) reversed fentanyl-induced increase in P co 2 (P =0.006), and decrease in P o 2 (P =0.015) and pH (P <0.001) in rats, and at 3 mg kg−1 s.c. reversed fentanyl-induced increase in P co 2 (P =0.007), and decrease in P o 2 (P =0.013) and S O 2 (P =0.036) in monkeys. Danavorexton increased minute volume and tidal volume in fentanyl-treated animals. Danavorexton at ≤10 mg kg−1 s.c. did not compromise fentanyl analgesia in rat formalin- and skin incision-induced pain models. Danavorexton promoted recovery from anaesthesia and fentanyl-induced sedation, and antagonised fentanyl-induced respiratory depression without compromising fentanyl analgesia. [ABSTRACT FROM AUTHOR]

Anaesthetists play a key role in the management of patients in the cardiac catheterization laboratory (cath lab), both for elective and emergency procedures. Safe and effective provision of anaesthesia relies on a thorough appreciation of the setup of the cath lab and an understanding of the ever-increasing range of procedures carried out in the angiography suite. This article provides an overview of general considerations for working in this challenging environment within the hospital, as well as outlining key cardiology subspecialties and their requisites for the anaesthetist: electrophysiology, structural, interventional, devices and mechanical circulatory support. [ABSTRACT FROM AUTHOR]

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Propofol is commonly used in ICUs, but its long-term effects have not been thoroughly studied. In vitro studies suggest it may harm mitochondrial function, potentially affecting clinical outcomes. This study aimed to investigate the association between substantial propofol sedation and clinical outcomes in critically ill patients. We conducted a single-centre cohort study of critically ill, mechanically ventilated (≥7 days) adults to compare patients who received a substantial dose of propofol (cumulative >500 mg) during the first week of ICU admission with those who did not. The primary outcome was the association between substantial propofol administration and 6-month mortality, adjusted for relevant covariates. Subanalyses were performed for administration in the early (day 1–3) and late (day 4–7) acute phases of critical illness due to the metabolic changes in this period. Secondary outcomes included tracheostomy need and duration, length of ICU and hospital stay (LOS), discharge destinations, ICU, hospital, and 3-month mortality. A total of 839 patients were enrolled, with 73.7 % receiving substantial propofol administration (substantial propofol dose group). Six-month all-cause mortality was 32.4 %. After adjusting for relevant variables, we found no statistically significant difference in 6-month mortality between both groups. There were also no significant differences in secondary outcomes. Our study suggests that substantial propofol administration during the first week of ICU stay in the least sick critically ill, mechanically ventilated adult patients is safe, with no significant associations found with 6-month mortality, ICU or hospital LOS, differences in discharge destinations or need for tracheostomy. [ABSTRACT FROM AUTHOR]

Alfaxalone is used in laboratory and companion rodents for sedation and anesthesia. The purpose of this study was to determine if 5 mg/kg alfaxalone administered intramuscularly provides safe and effective sedation for radiography in client-owned rats. Eleven rats were recruited. Heart rate, respiratory rate, and rectal temperature were measured prior to and during sedation. Reflexes (forelimb withdrawal, hind limb withdrawal, tail pinch, ear flick) were evaluated. Induction, sedation, and recovery quality were scored. Sedation depth was scored by 3 different observers based on video recordings. Ten minutes post-injection, thoracic radiographs were obtained. Nine rats were healthy, while two had mild respiratory signs. The mean (95% confidence interval [CI]) time to first effect was 3 (95%CI 1.3–4.7) minutes. Duration of sedation was 21.6 (95%CI 17.3–25.8) minutes. Vitals remained within clinically acceptable limits. Mild, self-limiting tremoring was noted in 3/11 rats. Reflexes tended to be preserved but were occasionally decreased or absent in some rats. Induction and recovery quality were very smooth in most rats. Radiographs were able to be performed in all rats. The time from radiographs to recovery was 4.7 (95%CI 1.4–8.1) minutes. Alfaxalone had rapid onset and recovery. It was effective for radiographic positioning, but an additional sedative could be considered in healthy rats to provide greater sedation depth and duration. The protocol appeared safe in a very small sample size of clinically ill rats, but further research is needed to confirm safety. [ABSTRACT FROM AUTHOR]

To observe the efficacy and safety of intranasal dexmedetomidine combined with midazolam in cranial magnetic resonance imaging of children. A prospective, observational, single-arm, one-center study. A total of 474 children were scheduled for cranial 3.0 T MRI at the first time. All patients were initially given 3 mcg/kg dexmedetomidine combined with 0.15 mg/kg midazolam. The one-time success rate, vital signs before and after treatment, onset time, recovery time, and incidence of adverse reactions were recorded. The one-time success rate was 78.1%. There were significant differences in respiration, heart rate, and blood oxygen saturation before and after treatment (P <.001). The onset time was 10 (8-15) minutes. The average recovery time was 2.58 ± 1.10 hours. Only 1.27% (6 cases) of adverse reactions were observed, including bradycardia (3 cases, 0.6%), tachycardia (1 case, 0.2%), and startle (2 cases, 0.4%). No special treatment was needed. The success of the examination was significantly correlated with age (OR 1.320, 95% CI 1.019-1.710, P =.035) and onset time (OR 0.959, 95% CI 0.921-0.998, P =.038). Dexmedetomidine 3 mcg/kg combined with midazolam 0.15 mg/kg intranasally has a good sedative effect in pediatric cranial magnetic resonance examinations, little impact on breathing and circulation, and few adverse reactions. Age and onset time are related factors affecting the one-time success rate. [ABSTRACT FROM AUTHOR]

The purpose of this American Gastroenterological Association (AGA) Institute Rapid Clinical Practice Update (CPU) Communication is to review the available evidence and provide expert advice regarding the evolving management of patients taking GLP-1 receptor agonists prior to endoscopy. This CPU was commissioned and approved by the AGA Institute Clinical Practice Updates Committee (CPUC) and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPUC and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in this field, and it reflects the experiences of the authors who are experts in bariatric medicine and/or endoscopy. [ABSTRACT FROM AUTHOR]

A preclinical study in animals has further characterised a new 'arousal' agent. Danavorexton (TAK-925) is an agonist for orexin receptor 2 where it promotes recovery from inhalational and i.v. anaesthesia and opioid sedation. Although danavorexton reverses opioid sedation, it does not compromise analgesia. This could be a useful addition to the postoperative drug cupboard. [ABSTRACT FROM AUTHOR]

The use of induction agents for rapid sequence intubation (RSI) has been associated with hypotension in critically ill patients. Choice of induction agent may be important and the most commonly used agents are etomidate and ketamine. This study aimed to compare the effects of a single dose of ketamine vs. etomidate for RSI on maximum Sequential Organ Failure Assessment (SOFA) score and incidence of hypotension. This single-center, randomized, parallel-group trial compared the use of ketamine and etomidate for RSI in critically ill adult patients in the emergency department. The study was performed under Exception from Informed Consent. The primary outcome was the maximum SOFA score within 3 days of hospitalization. A total of 143 patients were enrolled in the trial, 70 in the ketamine group and 73 in the etomidate group. Maximum median SOFA score for the ketamine group was 6.5 (interquartile range [IQR] 5–9) vs. 7 (IQR 5–9) for etomidate with no significant difference (–0.2; 95% CI –1.4 to 1.1; p = 0.79). The incidence of post-intubation hypotension was 28% in the ketamine group vs. 26% in the etomidate group (difference 2%; 95% CI –13% to 17%). There were no significant differences in intensive care unit outcomes. Thirty-day mortality rate for the ketamine group was 11% (8 deaths) and for the etomidate group was 21% (15 deaths), which was not statistically different. There were no significant differences in maximum SOFA score or post-intubation hypotension between critically ill adults receiving ketamine vs. etomidate for RSI. [ABSTRACT FROM AUTHOR]

Shoulder dislocations are among the most common orthopedic emergencies encountered in the emergency department (ED). Ultrasound-guided peripheral nerve blocks (USG-PNBs) are increasingly being used for acute pain management in the ED, but clinical evidence supporting their utility for shoulder dislocation is limited and often conflicting. The aim of this review was to summarize and evaluate the utility of USG-PNB for analgesia during closed reduction of dislocated shoulders in the ED. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic literature search of the PubMed, Scopus, and Cochrane databases was performed from database inception to September 2022. We included clinical studies examining USG-PNB for pain management of dislocated shoulders in the ED. Information collected from eligible studies included patient demographic characteristics, USG-PNB approach, alternate analgesia techniques, anesthetic regimens, clinical outcomes, and adverse events. Five studies met inclusion criteria, all of which were randomized controlled trials comparing USG-PNB with procedural sedation and analgesia. Pooled patient satisfaction scores were similar for both analgesia methods (3.5 ± 0.6 vs. 3.9 ± 0.6 out of 5; p = 0.76). Patients managed with procedural sedation and analgesia achieved higher rates of overall shoulder reduction (100% vs. 67%; p < 0.001) and successful reduction on the first attempt (86% vs. 48%; p < 0.001). The USG-PNB groups in all but one study had shorter lengths of ED stay. Overall, USG-PNB was associated with a lower risk of adverse events and complications (3.9% vs. 24.9%; p < 0.001), especially adverse respiratory events (0% vs. 14.7%; p < 0.001). USG-PNBs performed by adequately trained emergency physicians should be considered a safe and effective alternative for analgesia during closed reduction of dislocated shoulders in the ED, particularly in patients with cardiorespiratory comorbidities. [ABSTRACT FROM AUTHOR]

Pain management and sedation are necessary in severely burned persons. Balancing pain control, obtundation, and hemodynamic suppression can be challenging. We hypothesized that increased sedation during burn resuscitation is associated with increased intravenous fluid administration and hemodynamic instability. A retrospective review of a single burn center was performed from 2014 to 2019 for all admissions to the burn unit with > 20% total body surface area (TBSA) burns. Within 48 h of admission, we compared total amounts of sedation/pain medications (morphine milligram equivalents (MME), propofol, dexmedetomidine, benzodiazepines) with total resuscitation volumes and frequency of hypotensive episodes. Resuscitation volumes and frequency of hypotension were modeled with multivariable linear regression adjusting for burn severity and weight. 208 patients were included with median age of 43 years (IQR 29–55) and median %TBSA of 31 (IQR 25–44). Median 48-hour resuscitation milliliters per weight per %TBSA were 3.3 (IQR 2.28–4.92). Pain/sedative medications included a combination of opioids in 99%, benzodiazepines in 73%, propofol in 31%, and dexmedetomidine in 11% of patients. MMEs were associated with greater resuscitation volumes (95% CI: 0.15–0.54, p = 0.01) as well as number of hypotensive events (95% CI: 1.57–2.7, p < 0.001). No associations were noted with other sedative medications when comparing the number of hypotensive events and resuscitation volumes. Increased opioid administration has physiological consequences and should be carefully monitored during resuscitation as higher volume administrations lead to worse outcomes. Opioids and sedating medications should be titrated to the least amount needed to achieve reasonable comfort and sedation. • Increased opioids are significantly associated with increased hypotensive events. • Increased opioids are significantly associated with increased resuscitation volumes. • This association was not found with any other sedatives/pain medications. [ABSTRACT FROM AUTHOR]

To compare the effects of intramuscular premedication with a novel nonanalgesic [alfaxalone–midazolam–acepromazine (AMA)] and an analgesic [ketamine–midazolam–detomidine (KMD)] protocol on sedation end points and propofol requirements for induction of anesthesia in swine. Prospective experimental study. A total of 27 Yorkshire cross gilts weighing approximately 30 kg. Two sedation protocols, AMA and KMD, were compared. Time from intramuscular injection to ataxia, recumbency and nonresponsiveness to tactile stimulation was recorded. The propofol dose requirement for induction of general anesthesia and tracheal intubation, and any adverse events (paddling, twitching), were recorded. Data were tested for normality using a Shapiro–Wilk test. Propofol requirements were compared using a Student's t test. Times from injection to sedation end points were compared using a Mood's test, and significance was confirmed using a Kaplan–Meier curve with Wilcoxon test survival analysis. Sedation end points were reached significantly faster with KMD than with AMA. Nonresponsiveness occurred in 5 (0–16) and 9.5 (5–36) minutes for KMD and AMA, respectively (p = 0.011). No significant difference (p = 0.437) was found between propofol doses used in either group (KMD; 64.38 ± 5.98 mg, AMA; 72.00 ± 7.57 mg). More adverse events were noted with AMA (11/16 pigs) than with KMD (1/11 pigs). In pigs, AMA can be used as a reliable sedation protocol. Frequency of adverse events and time to reach sedation end points between AMA and KMD differed, but the dose of propofol needed to induce general anesthesia was not significantly different. [ABSTRACT FROM AUTHOR]

Cortical excitability is higher in unconsciousness than in wakefulness, but it is unclear how this relates to anaesthesia. We investigated cortical excitability in response to dexmedetomidine, the effects of which are not fully known. We recorded transcranial magnetic stimulation (TMS) and EEG in frontal and parietal cortex of 20 healthy subjects undergoing dexmedetomidine sedation in four conditions (baseline, light sedation, deep sedation, recovery). We used the first component (0–30 ms) of the TMS-evoked potential (TEP) to measure cortical excitability (amplitude), slope, and positive and negative peak latencies (collectively, TEP indices). We used generalised linear mixed models to test the effect of condition, brain region, and responsiveness on TEP indices. Compared with baseline, amplitude in the frontal cortex increased by 6.52 μV (P <0.001) in light sedation, 4.55 μV (P =0.003) in deep sedation, and 5.03 μV (P <0.001) in recovery. Amplitude did not change in the parietal cortex. Compared with baseline, slope increased in all conditions (P <0.02) in the frontal but not parietal cortex. The frontal cortex showed 5.73 μV higher amplitude (P <0.001), 0.63 μV ms−1 higher slope (P <0.001), and 2.2 ms shorter negative peak latency (P =0.001) than parietal areas. Interactions between dexmedetomidine and region had effects over amplitude (P =0.004) and slope (P =0.009), with both being higher in light sedation, deep sedation, and recovery compared with baseline. Transcranial magnetic stimulation-evoked potential amplitude changes non-linearly as a function of depth of sedation by dexmedetomidine, with a region-specific paradoxical increase. Future research should investigate other anaesthetics to elucidate the link between cortical excitability and depth of sedation. [ABSTRACT FROM AUTHOR]

• Emergency conversion from CS to GA during the procedure can occur, but its predictors and impact on clinical outcomes are not fully understood. • Atrial fibrillation and prolonged duration of procedure were identified as the independent predictors of emergency conversion to GA. • Emergency conversion to GA did not have any impact on the good functional outcome compared to CS at discharge or the rate of successful recanalization. Endovascular mechanical thrombectomy (EMT) for acute ischemic stroke can be conducted under conscious sedation (CS) or general anesthesia (GA). Emergency conversion from CS to GA during the procedure can occur, but its predictors and impact on clinical outcomes are not fully understood. A single centre retrospective analysis was conducted on 226 patients who underwent EMT for anterior circulation stroke. Two groups were identified: patients who completed the procedure under CS and those requiring emergency conversion to GA. The predictors of emergency conversion to GA and its impact on clinical outcomes were analyzed. Forty-five patients (19.9%) required conversion to GA. Atrial fibrillation (OR 2.38; CI 1.09–5.22; p = 0.03) and prolonged duration of procedure (OR 1.02; CI 1.01–1.04; p < 0.001) were identified as the independent predictors of emergency conversion to GA. Patients with atrial fibrillation and prolonged duration of procedure especially when utilizing combined aspiration-stent retriever or angioplasty/stenting techniques, had a higher likelihood of requiring emergency conversion to general anesthesia (GA). [ABSTRACT FROM AUTHOR]

In pediatric imaging, sedation is often necessary to obtain diagnostic quality imaging. We aim to quantify patient and imaging-specific factors associated with successful pediatric scans without anesthesia and to evaluate labor cost savings associated with our institutional Scan Without Anesthesia Program (SWAP). Patients who participated in SWAP between 2019-2022 were identified. Chart review was conducted to obtain sociodemographic and clinical information. Radiology database was used to obtain scan duration, modality/body part of examination, and administration of contrast. Mann-Whitney U and Chi-Square tests were used for univariate analysis of factors associated with success. Multivariate logistic regression was used to evaluate independent contributions to success. Associated hospital labor cost savings were estimated using salary information obtained through publicly available resources. Of 731 patients, 698 had successful and 33 had unsuccessful scans (95% success rate). In univariate analysis, older age, female sex, absence of developmental delay, and administration of contrast were significantly associated with successful scans. Multivariate analyses revealed that older age, female sex, and absence of developmental delay were significant independent factors lending toward success. Imaging-related factors were not associated with outcome in multivariate analysis. Estimated labor cost savings were $139,367.80 per year for the medical center. SWAP had an overall success rate of 95%. Older age, absence of developmental delay, and female sex were independently significantly associated with successful outcome. Cost analysis reveals substantial labor cost savings to the institution compared with imaging under anesthesia. [ABSTRACT FROM AUTHOR]

Succinylcholine and rocuronium are the most commonly utilized neuromuscular blocker agents (NMBAs) for rapid sequence intubation (RSI) in the emergency department (ED). The duration of action of rocuronium is significantly longer (∼30 min) compared to succinylcholine (∼10 min) and previous studies have shown that patients receiving rocuronium are more likely to have longer time to sedation initiation following RSI. Furthermore, patients receiving rocuronium may be more likely to experience awareness with paralysis than those receiving succinylcholine. The primary goal for this study was to evaluate the association between NMBA use during RSI and post-intubation sedation and analgesia practices in the ED. This was a retrospective, multicenter cohort study including patients 18 years and older that received succinylcholine or rocuronium during RSI in the ED between September 1, 2020 and August 31, 2021. Patients were excluded if they were intubated prior to ED arrival, experienced an out-of-hospital or in ED cardiac arrest, or received sugammadex within 60 min of rocuronium administration. Patients were screened in reverse chronological order until the targeted sample size was achieved and all data was abstracted from the electronic health record. The primary outcome was the time to initiation of analgesia or sedation. Secondary outcomes included dose of sedatives or analgesia administered at 30- and 60 min, and medications administered for post-intubation sedation or analgesia. A total of 200 ED patients were included of which 100 received succinylcholine and 100 received rocuronium. There was no difference in the median time to initiation of analgesia or sedation between the succinylcholine and rocuronium groups (10 vs 8.5 min, p = 0.82) or in Kaplan-Meier cumulative probabilities (p = 0.17). At 60 min post-RSI, those receiving succinylcholine received significantly higher median doses of propofol (20 μg/kg/min vs. 10 μg/kg/min; p = 0.02) and fentanyl [100 μg vs. 84.2 μg; p = 0.02]. While no differences were observed in the time to initiation of post-intubation sedation or analgesia in ED patients receiving succinylcholine compared to rocuronium, differences in the intensity of post-intubation regimens was observed. Further investigation is needed to evaluate the adequacy of sedation following RSI in the ED. [ABSTRACT FROM AUTHOR]

Dexmedetomidine (DEX) provides a unique conscious sedation without respiratory depression. We examined the usefulness of intravenous (IV) DEX sedation combined with brachial plexus block for long-duration upper extremity surgery without an anesthesiologist. We retrospectively reviewed 90 limbs of 86 patients and measured the actual operative time course in detail. The adverse events and the patient-reported outcomes regarding intraoperative pain and depth of sedation were evaluated. The mean total time of the operation, tourniquet use, and the IV DEX sedation were 150 min, 132 min, and 117 min, respectively. The mean time between discontinuation of IV DEX sedation and completion of the operation was 51 min. The intraoperative adverse events involved bradycardia (21%), hypotension (18%), and oxygen desaturation (3%). The mean visual analog scale scores of pain during brachial plexus block, surgical site pain, tourniquet pain, and depth of the sedation were 23.4 mm, 0.14 mm, 4.2 mm, and 6.6 mm, respectively. Furthermore, 96% patients expressed a preference for receiving anesthesia as brachial plexus block with IV DEX sedation. Long-duration upper extremity surgery, even longer than 2 h, was feasible under brachial plexus block combined with IV DEX sedation without an anesthesiologist. For patients with low blood pressure and/or low heart rate, it is recommended to adjust the continuous infusion of IV DEX to less than 0.4 µg/kg/h. To ensure that the patients are able to promptly leave the operating room fully awake, IV DEX infusion should be stopped at least 30 min before finishing the operation. [ABSTRACT FROM AUTHOR]

Sedation of critically ill patients with inhaled anaesthetics may reduce lung inflammation, time to extubation, and ICU length of stay compared with intravenous (i.v.) sedatives. However, the impact of inhaled anaesthetics on cognitive and psychiatric outcomes in this population is unclear. In this systematic review, we aimed to summarise the effect of inhaled anaesthetics on cognitive and psychiatric outcomes in critically ill adults. We searched MEDLINE, EMBASE, and PsycINFO for case series, retrospective, and prospective studies in critically ill adults sedated with inhaled anaesthetics. Outcomes included delirium, psychomotor and neurological recovery, long-term cognitive dysfunction, ICU memories, anxiety, depression, post-traumatic stress disorder (PTSD), and instruments used for assessment. Thirteen studies were included in distinct populations of post-cardiac arrest survivors (n =4), postoperative noncardiac patients (n =3), postoperative cardiac patients (n =2), and mixed medical–surgical patients (n =4). Eight studies reported delirium incidence, two neurological recovery, and two ICU memories. One study reported on psychomotor recovery, long-term cognitive dysfunction, anxiety, depression, and PTSD. A meta-analysis of five trials found no difference in delirium incidence between inhaled and i.v. sedatives (relative risk 0.95 [95% confidence interval: 0.59–1.54]). Compared with i.v. sedatives, inhaled anaesthetics were associated with fewer hallucinations and faster psychomotor recovery but no differences in other outcomes. There was heterogeneity in the instruments used and timing of these assessments. Based on the limited evidence available, there is no difference in cognitive and psychiatric outcomes between adults exposed to volatile sedation or intravenous sedation in the ICU. Future studies should incorporate outcome assessment with validated tools during and after hospital stay. PROSPERO CRD42021236455. [ABSTRACT FROM AUTHOR]

Sedation is a technique that can be employed to assist selected patients to undergo dental procedures that may otherwise be difficult for them to tolerate in a fully conscious state. Safe sedation requires attention to patient selection, the clinical environment, level of physiological monitoring, sedation technique, and postoperative management. Various sedative pharmacological agents are available, and can be used alone or in combination. General anaesthetic agents used in lower doses for this purpose should be short-acting and carefully titrated, to allow fine control of sedation and a greater chance of success. Inadvertent overdosage is a potential risk, therefore, these particular agents must be administered by an anaesthetist. Alternatively, Entonox and oral or intravenous benzodiazepines can be safely administered by other appropriately trained practitioners. [ABSTRACT FROM AUTHOR]

• Magnetic resonance imaging (MRI) procedure require patients to remain still in a confined space for long periods. This can be extremely difficult for pediatric patients. • The music or the mother's voice would reduce the need for sedatives during MRI. • To listen to the mother's voice during MRI in pediatric patients reduced the total sedative requirement consumed without increasing the depth of sedation. • The mother's voice is non-pharmacological, easily accessible. The mother's voice does not have any side effects. Magnetic resonance imaging examinations frequently cause anxiety and fear in children. The objective of this study was to investigate the effects of listening to music sound, the mother's voice, and sound isolation on the depth of sedation and need for sedatives in pediatric patients who would undergo MRI. Ninety pediatric patients aged 3 to 12 years who were planned for imaging in the MRI unit were randomly assigned to isolation group (Group I), musical sound group (Group II), and mother's voice group (Group III). We evaluated patients' anxiety and sedation levels via the Observer's Assessment of Alertness/Sedation (OAA/S) Heart rate, oxygen saturation, OAA/S, and Ramsey scores during the procedure were not significantly different among the groups (p >0.05). The mean amount of propofol and total propofol consumption was statistically lower in the mother's voice group than in the isolation and music sound groups (p <0.001). Mean propofol amount and total propofol consumption were not significantly different in isolation and music sound groups (p >0.05). No difference was found between the groups regarding the time it took for the patients' Modified Aldrete score to reach 9 (p >0.05). In pediatric patients, listening to the mother's voice during MRI decreased the total sedative requirement consumed without increasing the depth of sedation. [ABSTRACT FROM AUTHOR]

Sedative premedication in children may negatively impact their cardiorespiratory status during the perioperative course, and no clear consensus exists on the optimal premedication treatment for pediatric patients. The objective was to compare the perioperative cardiorespiratory responses to sedation using three different sedative premedication regimens in preschool children scheduled for surgery with total intravenous anesthesia. A single-center randomized controlled trial. This is a planned secondary analysis of a study conducted at a 200-bed tertiary referral hospital. Ninety children participated in the study. They were aged 2–6 years and scheduled for ear, nose, and throat surgery with propofol/remifentanil anesthesia. Participants were randomly assigned to receive oral midazolam 0.5 mg/kg-1 (MID), oral clonidine 4 mcg/kg–1 (CLO), or intranasal dexmedetomidine 2 mcg/kg-1 (DEX). The main outcome measures were the sedation level, based on the Ramsay Sedation Scale (RSS), and cardiorespiratory status, monitored during the perioperative period. The final cohort had 83 children (MID, n =27; CLO, n =26; DEX, n =30), with similar intergroup patient characteristics. RSS scores were lower in the MID group than in the CLO and DEX groups before induction and within 30 min postsurgery (P <0.001 and P =0.006, respectively). A negative correlation existed between the RSS and heart rate (HR) (r =-0.570, P <0.001). Before anesthesia induction, the respiratory rate was lowest in the DEX group (MID 21.5±1.7 min–1, CLO 20.6±2.6 min–1, DEX 20.2±1.7 min–1; P =0.042). The HR was lower in the CLO and DEX groups than in the MID group (MID, 102.8±10.0 min–1; CLO, 87.4±9.6 min–1; DEX, 87.6±7.9 min–1; P <0.001). The HR was lower immediately after induction (P =0.009) and intraoperatively (P =0.025) in the CLO and DEX groups than in the MID group. When used as premedication before propofol/remifentanil anesthesia, clonidine and dexmedetomidine provided deeper preoperative sedation compared to midazolam. From a clinical perspective, all three study drugs provided essentially stable cardiovascular and respiratory conditions during the entire perioperative period. [ABSTRACT FROM AUTHOR]

Veterinary care of the domestic ferret often utilizes chemical restraint for venipuncture, radiographs, and ultrasonography. Common forms of chemical restraint for ferrets include inhalant anesthetics and parenteral sedatives. Disadvantages of these forms of chemical restraint include adverse patient reaction and environmental contamination for inhalant anesthetics while small muscle mass and patient reactivity are challenging for intramuscular injections. Alfaxalone is a unique neurosteroid anesthetic that can be used as an induction agent intravenously and a sedative agent intramuscularly and subcutaneously. Subcutaneous injection appears to be well tolerated in small exotic species due to the increased volume the subcutaneous space can accommodate as well as the ease of administration. A randomized, blinded, complete crossover study evaluating two doses (10 mg/kg and 12.5 mg/kg) of subcutaneous (SC) alfaxalone alone was performed in 10 clinically healthy ferrets (5 neutered males and 5 spayed females). Once alfaxalone was administered sedation scores (body posture, righting reflex, jaw tone, front limb withdrawal, and toe pinch) and vital parameters (heart rate, respiratory rate, rectal temperature, SpO 2 and blood pressure) were evaluated at regular intervals. Sedation characterized by the loss of righting reflex for more than ten minutes was observed in 90% of ferrets in both groups. The higher dose of alfaxalone (12.5 mg/kg) produced a statistically significant increase in the duration of sedation, as well as in the values of all sedation scores. Temperature significantly decreased over time for both groups, while SpO 2 and respiratory rate did not display any significant changes. At both doses, no cardiovascular depression was noted but there were significant increases in heart rate and blood pressure parameters. Subcutaneous alfaxalone in ferrets produces adequate sedation characterized by the loss of righting reflex and easy limb manipulation with no significant adverse effects. This type of sedation is appropriate for noninvasive procedures such as a physical exam, ultrasonography, and radiographic positioning without manual restraint. The limitations for SC alfaxalone, as a sole sedative agent, include the variable range in times to onset and variable durations of sedation. [ABSTRACT FROM AUTHOR]

Caffeine is the most consumed psychoactive substance worldwide. Previous studies suggested higher caffeine consumption in subjects with schizophrenia spectrum disorders (SSD) as well as associations with symptoms, medication and medication side-effects. In a large and well-characterized sample of SSD subjects we explored the association between caffeine consumption and clinical (psychosis related, severity, general health) as well as pharmacological (antipsychotic treatment, sedation potential) variables. Eight hundred four subjects with data on their caffeine (coffee and tea) consumption successively recruited were included in this study. After controlling for potential confounders (demographic variables, smoking) only the negative dimension of psychosis was associated with the amount of caffeine ingested. Less severe negative symptoms were associated with higher caffeine consumption. The effect size of this association was small (partial correlation coefficient = −0.12) but significant. • Higher caffeine consumption was associated with lower negative symptoms. • This association was still significant after adjustment for multiple confounders. • A more sedative treatment was associated with higher caffeine consumption. • Taking into account smoking the association with treatment was no more significant. • Caffeine consumption was not associated with anxiety or quality of sleep. [ABSTRACT FROM AUTHOR]

To evaluate the pharmacodynamic effects and pharmacokinetics of a single intramuscular (IM) injection of alfaxalone in central bearded dragons (Pogona vitticeps) when injected at a cranial versus a caudal site. Prospective, masked, randomized crossover study. A total of 13 healthy bearded dragons weighing 0.48 ± 0.1 kg. Alfaxalone (10 mg kg–1) was administered IM to 13 bearded dragons in the triceps muscle (cranial treatment) or the quadriceps muscle (caudal treatment) separated by 4 weeks. Pharmacodynamic variables included movement score, muscle tone score and righting reflex. Blood was obtained from the caudal tail vein using a sparse sampling methodology. Plasma alfaxalone concentrations were determined using liquid chromatography–mass spectrometry, and pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. Differences in variables between injection sites were analyzed using a nonparametric Wilcoxon signed-rank test for paired data with significance set at p ≤ 0.05. Time to loss of righting reflex score was not different, median (interquartile range), between cranial and caudal treatments [8 (5–11) and 8 (4–12) minutes, respectively, p = 0.72]. Time to recovery of righting reflex was also not different between cranial and caudal treatments [80 (44–112) and 64 (56–104) minutes, respectively, p = 0.75]. Plasma alfaxalone concentrations were not significantly different between treatments. The population estimate (95% confidence intervals) for volume of distribution per fraction absorbed was 1.0 (0.79–1.20) L kg–1, clearance per fraction absorbed was 9.6 (7.6–11.6) mL minute–1 kg–1, absorption rate constant was 2.3 (1.9–2.8) minute–1 and elimination half-life was 71.9 (52.7–91.1) minutes. Regardless of the injection site, IM alfaxalone (10 mg kg–1) produced reliable chemical restraint in central bearded dragons, appropriate for nonpainful diagnostic procedures or anesthetic premedication. [ABSTRACT FROM AUTHOR]

To investigate the relationship between urine specific gravity (USG) and the risk of arterial hypotension during general anaesthesia (GA) in healthy dogs premedicated with dexmedetomidine and methadone. Prospective clinical cohort study. A total of 75 healthy client-owned dogs undergoing GA for elective tibial plateau levelling osteotomy. After placing an intravenous catheter, dogs were premedicated with dexmedetomidine (5 μg kg–1) and methadone (0.3 mg kg–1) intravenously. After induction of GA with alfaxalone to effect, the bladder was expressed and USG measured. An arterial catheter was placed, and residual blood was used to measure packed cell volume (PCV) and total protein (TP). GA was maintained with isoflurane vaporised in oxygen and a femoral and sciatic nerve block were performed. Arterial blood pressure < 60 mmHg was defined as hypotension and recorded by the anaesthetist. Treatment for hypotension was performed in a stepwise manner following a flow chart. Frequency of hypotension, treatment and response to treatment were recorded. Logistic regression modelling was used to assess the association between USG, TP and PCV and incidence of perioperative hypotension; p < 0.05. Data from 14 dogs were excluded. Of the 61 dogs, 16 (26%) were hypotensive during GA, 15 dogs needed treatment of which 12 were responsive to a decrease in inhalant vaporiser setting. The logistic regression model was not statistically significant (p = 0.8). There was no significant association between USG (p = 0.6), TP (p = 0.4), PCV (p = 0.8) and arterial hypotension during GA. In healthy dogs premedicated with dexmedetomidine and methadone and maintained under GA with isoflurane and a femoral and sciatic nerve block, there was no relationship between the specific gravity of urine collected after premedication and intraoperative arterial hypotension. [ABSTRACT FROM AUTHOR]

Conscious states are typically inferred through responses to auditory tasks and noxious stimulation. We report the use of a stimulus-free behavioural paradigm to track state transitions in responsiveness during dexmedetomidine sedation. We hypothesised that estimated dexmedetomidine effect-site (Ce) concentrations would be higher at loss of responsiveness (LOR) compared with return of responsiveness (ROR), and both would be lower than comparable studies that used stimulus-based assessments. Closed-Loop Acoustic Stimulation during Sedation with Dexmedetomidine data were analysed for secondary analysis. Fourteen healthy volunteers were asked to perform the breathe–squeeze task of gripping a dynamometer when inspiring and releasing it when expiring. LOR was defined as five inspirations without accompanied squeezes; ROR was defined as the return of five inspirations accompanied by squeezes. Brain states were monitored using 64-channel EEG. Dexmedetomidine was administered as a target-controlled infusion, with Ce estimated from a pharmacokinetic model. Counter to our hypothesis, mean estimated dexmedetomidine Ce was lower at LOR (0.92 ng ml−1; 95% confidence interval: 0.69–1.15) than at ROR (1.43 ng ml−1; 95% confidence interval: 1.27–1.58) (paired t -test; P =0.002). LOR was characterised by progressively increasing fronto-occipital EEG power in the 0.5–8 Hz band and loss of occipital alpha (8–12 Hz) and global beta (16–30 Hz) power. These EEG changes reverted at ROR. The breathe–squeeze task can effectively track changes in responsiveness during sedation without external stimuli and might be more sensitive to state changes than stimulus-based tasks. It should be considered when perturbation of brain states is undesirable. NCT04206059. [ABSTRACT FROM AUTHOR]

• The AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy;. • Adenomas in the splenic flexure and descending colon were more frequently missed;. • There was no such difference in the high-level endoscopists. Deep-sedated colonoscopy with propofol is widely used in China. However, its impact on quality metrics remains controversial. We aimed to investigate the effects of deep-sedated colonoscopy on missed adenomas, specifically in each colorectal segment. Data of 3710 individuals from seven hospitals in China who underwent an initial colonoscopy with or without propofol sedation and a second colonoscopy without sedation within six months for surveillance or polypectomy by endoscopist of the same level between October 2020 and September 2021 were retrospectively analyzed. A total of 1113 missed adenomas in 3710 patients were evaluated. The adenoma miss rate (AMR) was significantly higher in deep-sedated colonoscopy than in unsedated colonoscop [19.14% (578/3020) vs. 16.15% (535/3313), P < 0.05]. The risk of missing adenomas in deep-sedated colonoscopy was 1.229 times higher than in unsedated colonoscopy (OR, 1.229; 95% CI: 1.080–1.399). AMRs of the splenic flexure (26.02% [96/369] vs. 16.04% [47/293], P < 0.05) and descending colon (20.86% [102/489] vs. 13.37% [54/404], P < 0.05) were significantly higher in deep-sedated colonoscopy than in unsedated colonoscopy when performed by middle-level endoscopists rather than high-level endoscopists (P < 0.05). AMR was higher in deep-sedated colonoscopy than in unsedated colonoscopy. Furthermore, adenomas in the splenic flexure and descending colon were more frequently missed in deep-sedated colonoscopy than in unsedated colonoscopy, particularly when performed by less experienced endoscopists. [ABSTRACT FROM AUTHOR]

Examine the efficacy and safety of perioperative gabapentin in bariatric surgical patients. Systematic Review and Meta-analysis. An exhaustive search was conducted using PubMed, Cochrane Library, MEDLINE, CINAHL, Google Scholar, and other gray literature. Only randomized controlled trials evaluating the use of gabapentin in bariatric surgery were included. Risk ratio (RR) and mean difference (MD) were used to estimate outcomes with suitable effect models. Quality of evidence was assessed using the Risk of Bias and GRADE system. Four trials consisting of 283 patients were analyzed. The use of gabapentin significantly lowered the cumulative pain score in the first 24 hours after surgery by an average of 1.04 (MD, –1.04; 95% CI, –1.45 to –0.63; P <.00001). Gabapentin also reduced the overall morphine equivalent consumption by 7.89 mg (MD, –7.89; 95% CI, –13.56 to –2.2; P =.006). However, gabapentin did not affect the incidence of PONV (RR, 0.61; 95% CI, 0.38-1.00; P =.05), somnolence (RR, 1.25; 95% CI, 0.57-2.73; P =.57), dizziness (RR, 1.01; 95% CI, 0.40-2.54; P =.99), and headache (RR, 0.76; 95% CI, 0.25-2.30; P =.62). Substantial heterogeneity, imprecision of the effect size, and potential publication bias were limitations of this review. The use of gabapentin is effective in the management of postoperative pain in bariatric surgery. However, there is limited data regarding the opioid-sparing effect and adverse effect profiles of gabapentin in the bariatric surgical population. [ABSTRACT FROM AUTHOR]

Gabapentin is used to treat seizures, neuropathic pain, and anxiety. Currently, dosage recommendations for rabbits are extrapolated from other species. The objective of this study was to determine the pharmacokinetics of gabapentin after single, oral administration in domestic rabbits. A randomized, crossover study was performed in male (n = 3) and female (n = 3) rabbits after administration of either 25 or 50 mg/kg gabapentin orally. Plasma concentrations of gabapentin were measured at 0, 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24, and 48 hours post-administration via liquid chromatography. Mean maximum plasma concentrations were 17.70 and 16.83 µg/mL for the 25 and 50 mg/kg doses, respectively. Mean times to maximum plasma concentration were 1.75 and 1.5 hours, and mean terminal half-lives were 10.2 and 9.44 hours for the 25 and 50 mg/kg doses, respectively. No adverse effects observed at either dose. A single oral dose of gabapentin at 50 mg/kg did not result in higher plasma concentrations compared to the 25 mg/kg dose and no differences were observed between males and females for either dosing group (P > 0.9). [ABSTRACT FROM AUTHOR]

An increasing number of patients are receiving sedation or anaesthesia in locations outside of the operating room. Compared with the operating room, anaesthesia providers working in a non-operating room anaesthesia (NORA) location report significantly lower perceived levels of safety, and higher levels of anxiety, stress, and workload. These results are likely to affect the well-being of staff in NORA locations and are clinically relevant in terms of patient safety. [ABSTRACT FROM AUTHOR]

• The use of a checklist improved protocol adherence for diagnosis of death by neurologic criteria/brain death and did not increase time to declaration of death. • Metabolic and toxic confounders are common to encounter in patients who progress to death by neurologic criteria/brain death. • The clinical diagnosis of death by neurologic criteria/brain death is commonly limited by the inability to complete apnea testing, and these cases require appropriate ancillary testing. To determine the effect on adherence to an institutional death by neurological criteria/brain death (DNC/BD) policy of implementation of a standardized DNC/BD checklist in the electronic medical record (EMR). The retrospective study cohort included all patients admitted to our institution who were declared dead by neurologic criteria determined by ICD code (G93.82) between June 2015 and October 2019. Two investigators independently reviewed each case for adherence with institutional policy, and agreement was assessed using unweighted kappa statistics. Patient data and adherence to institutional policy before and after implementation of a standardized DNC/BD checklist were compared. There were 66 patients identified by the initial search and 38 were included in the final analysis, with 19 cases in both the pre- and post- checklist periods. There were no significant differences in age, cause of DNC/BD, time to DNC/BD determination, potential toxic, metabolic, physiologic confounders, or use of ancillary testing. The pre-checklist period adherence was 47.4% (n = 9/19) versus 94.6% (n = 18/19; p = 0.001) in the post-checklist EMR DNC/BD period. Implementation of a standardized EMR checklist substantially improved DNC/BD policy adherence in our institution. This study provides Class IV evidence on the use of standardized EMR checklist to improve death by neurologic criteria/brain death policy adherence. [ABSTRACT FROM AUTHOR]

Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0–8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques. Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0–8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events. Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91–0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92–0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14–0.65); for oral pentobarbital 99% (95% CI: 0.90–1.00); for rectal thiopental 92% (95% CI: 0.85–0.96); for oral melatonin 75% (95% CI: 0.54–0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38–0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78–0.99); and for inhaled sevoflurane 98% (95% CI: 0.97–0.99). We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%. [ABSTRACT FROM AUTHOR]