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\"Continuous sedation until death (sometimes referred to as terminal sedation or palliative sedation) is an increasingly common practice in end-of-life care. However, it raises numerous medical, ethical, emotional and legal concerns, such as the reducing or removing of consciousness (and thus potentially causing 'subjective death'), the withholding of artificial nutrition and hydration, the proportionality of the sedation to the symptoms, its adequacy in actually relieving symptoms rather than simply giving onlookers the impression that the patient is undergoing a painless 'natural' death, and the perception that it may be functionally equivalent to euthanasia. This book brings together contributions from clinicians, ethicists, lawyers and social scientists, and discusses guidelines as well as clinical, emotional and legal aspects of the practice. The chapters shine a critical spotlight on areas of concern and on the validity of the justifications given for the practice, including in particular the doctrine of double effect\"-- Provided by publisher.

BackgroundAlthough gastrointestinal endoscopy with sedation is increasingly performed in older patients, the optimal level of sedation remains open to debate. In this study, our objective was to compare the effects of moderate sedation (MS) and deep sedation (DS) on recovery following outpatient gastroscopy in elderly patients.MethodsIn this randomized, partially blinded, controlled trial, we randomly divided 270 patients older than 60 years who were scheduled for elective outpatient gastroscopy into the MS or DS group based on the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale. The primary outcome was the duration of stay in the post-anesthesia care unit (PACU). Secondary outcomes included the duration of the total hospital stay, frequency of retching, bucking, and body movements during the examination, endoscopist and patient satisfaction, and sedation-associated adverse events during the procedure.ResultsA total of 264 patients completed the study, of whom 131 received MS and 133 received DS. MS was associated with a shorter PACU stay [16.15 ± 9.01 min vs. 20.02 ± 11.13 min, P < 0.01] and total hospital stay [27.32 ± 9.86 min vs. 30.82 ± 12.37 min, P < 0.05], lesser hypoxemia [2.3% (3/131) vs. 12.8% (17/133), P < 0.01], use of fewer vasoactive drugs (P < 0.001), and more retching (P < 0.001). There was no difference in the incidence of bucking and body movements or endoscopist and patient satisfaction between the two groups.ConclusionCompared to deep sedation, moderate sedation may be a preferable choice for American Society of Anesthesiologists (ASA) Grade I–III elderly patients undergoing outpatient gastroscopies, as demonstrated by shorter PACU stays and total hospital stays, lower sedation-associated adverse events, and similar levels of endoscopist and patient satisfaction.

Sedation is required to perform endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) given the duration and complexity of these advanced procedures. Sedation options include anesthetist-directed sedation (ADS) vs. gastroenterologist-directed sedation (GDS). Although ADS has been shown to shorten induction and recovery times, it is not established whether it impacts likelihood of procedure completion. Our aim was to assess whether ADS impacts the success of advanced endoscopy procedures. We prospectively assessed the sedation strategy for patients undergoing ERCP and EUS between October 2010 and October 2013. Although assignment to ADS vs. GDS was not randomized, it was determined by day of the week. A sensitivity analysis using propensity score matching was used to model a randomized trial. The main outcome, procedure failure, was defined as an inability to satisfactorily complete the ERCP or EUS such that an additional endoscopic, radiographic, or surgical procedure was required. Failure was further categorized as failure due to inadequate sedation vs. technical problems. During the 3-year study period, 60% of the 1,171 procedures were carried out with GDS and 40% were carried out with ADS. Failed procedures occurred in 13.0% of GDS cases compared with 8.9% of ADS procedures (multivariate odds ratio (OR): 2.4 (95% confidence interval (CI): 1.5-3.6)).This was driven by a higher rate of sedation failures in the GDS group, 7.0%, than in the ADS group, 1.3% (multivariate OR: 7.8 (95% CI: 3.3-18.8)). There was no difference in technical success between the GDS and ADS groups (multivariate OR: 1.2 (95% CI: 0.7-1.9)). We were able to match 417 GDS cases to 417 ADS cases based on procedure type, indication, and propensity score. Analysis of the propensity score-matched patients confirmed our findings of increased sedation failure (multivariate OR: 8.9 (95% CI: 2.5-32.1)) but not technical failure (multivariate OR: 1.2 (0.7-2.2)) in GDS compared with ADS procedures. Adverse events of sedation were rare in both groups. Failed ERCP in the GDS group resulted in a total of 93 additional days of hospitalization. We estimate that $67,891 would have been saved if ADS had been used for all ERCP procedures. No statistically significant difference in EUS success was identified, although this sub-analysis was limited by sample size. ADS improves the success of advanced endoscopic procedures. Its routine use may increase the quality and efficiency of these services.

Procedural sedation and analgesia (PSA) are a common practice in emergency departments (EDs), aiming to alleviate pain, anxiety, and discomfort during various medical procedures. We have undertaken a systematic review and meta-analysis with the aim of assessing the incidence of adverse events associated with PSA, including those related to individual drugs and various drug combinations. The study adhered to PRISMA guidelines for a systematic review and meta-analysis of adverse events in ED sedation. A comprehensive search strategy was employed across ten databases, supplemented by searches on clinicaltrials.gov and manual reviews of reference lists. Data extraction focused on medication administration and adverse events. The study considered four types of adverse events: cardiac, respiratory, gastrointestinal, and neurological. Only randomized controlled trials (RCTs) focusing on PSA administered to adult patients within the ED setting were included. The statistical analysis employed OpenMeta Analyst to conduct a one-arm meta-analysis, with findings presented alongside their corresponding 95% Confidence Intervals. Forest plots were constructed to combine and evaluate results, and sensitivity analyses were performed to identify sources of heterogeneity. From a literature search of 4246 records, 32 RCTs were deemed suitable for this meta-analysis. The analysis included 6377 procedural sedations. The most common adverse event was hypoxia, with an incidence rate of 78.5 per 1000 sedations (95% CI = 77.5–133.5). This was followed by apnea and hypotension, with incidence rates of 31 (95% CI = 19.5–41.8) and 28.1 (95% CI = 17.4–38.9) per 1,000 sedations, respectively. Agitation and vomiting each occurred in 15.6 per 1,000 sedations (95% CI = 8.7–22.6). Severe adverse events were rare, with bradycardia observed in 16.7 per 1,000 sedations, laryngospasm in 2.9 per 1,000 sedations (95% CI =  – 0.1 to 6), intubation in 10.8 per 1,000 sedations (95% CI = 4–17), and aspiration in 2.7 per 1,000 sedations (95% CI =  – 0.3 to 5.7). Ketamine is found to be the safest option in terms of respiratory adverse events, with the lowest rates of apnea and hypoxia, making it the least respiratory depressant among the evaluated drugs. Etomidate has the least occurrence of hypotension when used alone. Propofol has the highest incidence of hypotension when used alone and ranks second in hypoxia-related adverse events after midazolam. Using combinations of sedating agents, such as propofol and ketamine, has been found to offer several advantages over single drugs, especially in reducing adverse events like vomiting, intubation difficulty, hypotension, bradycardia, and laryngospasm. The combination significantly reduces the incidence of hypotension compared to using propofol or ketamine individually. Despite the regular use of procedural sedation, it can sometimes lead to serious adverse events. Respiratory issues like apnea and hypoxia, while not common, do occur more often than cardiovascular problems such as hypotension. However, the least frequent respiratory complications, which can also pose a threat to life, include laryngospasm, aspiration, and intubation. These incidents are extremely rare.

Ciprofol, a novel intravenous anesthetic, provides rapid recovery in patients undergoing colonoscopy. We aimed to examine the efficacy and safety of ciprofol in comparison with propofol for sedation or anesthesia in non-operating room settings including endoscopic submucosal dissection, endoscopic retrograde cholangiopancreatography, and flexible bronchoscopy (FB). Prospective, randomized, double-blind, parallel-group clinical trial. University-affiliated teaching hospital. We recruited 207 patients scheduled for an endoscopic procedure from October 2021 to December 2021. Patients were randomized into three groups according to the dose during induction (n = 69 each): 1) ciprofol 6 mg/kg/h, 2) ciprofol 8 mg/kg/h, or 3) propofol 40 mg/kg/h. Ciprofol or propofol was administered throughout the procedure. The primary outcome was the success rate of sedation or anesthesia for the procedures. Secondary outcomes included induction time, endoscope insertion time, recovery time, discharge time, incidence of drug-related adverse events (AEs), neurological and inflammatory outcomes. The procedure success rates in the three groups were 100%. The induction time in the 6 (3.3 ± 1.0 min) and 8 mg/kg/h (2.9 ± 0.6 min) ciprofol groups was longer than that in the propofol group (2.5 ± 0.6 min) only in patients undergoing FB (p = 0.004). The time for patients to be fully alert and discharged from the post-anesthesia care unit was comparable across the three groups (p > 0.05). The incidence of drug-related AEs in the propofol and 6 and 8 mg/kg/h ciprofol groups was 84.1%, 76.8%, and 79.7%. No pain on injection was reported by ciprofol groups. Neurological outcomes and inflammatory responses were comparable among the three groups. Ciprofol induced a level of sedation or anesthesia equivalent to that induced by propofol in non-operating room settings except for a prolonged induction time in patients undergoing FB. Ciprofol had a safety profile similar to that of propofol. No pain on injection was reported by ciprofol. •Ciprofol, a novel intravenous anesthetic, and propofol induced equivalent sedation or anesthesia in non-operating room settings.•Ciprofol had a similar safety profile to that of propofol.•No pain on injection was reported by the ciprofol groups.•Ciprofol and propofol anesthesia had similar neurological outcomes and inflammatory parameters.

Objectives We sought to study the association between sedation status, medications (benzodiazepines, opioids, and antipsychotics), and clinical outcomes in a resource-limited setting. Design A longitudinal study of critically ill participants on mechanical ventilation. Setting Five intensive care units (ICUs) in four public hospitals in Lima, Peru. Patients One thousand six hundred fifty-seven critically ill participants were assessed daily for sedation status during 28 days and vital status by day 90. Results After excluding data of participants without a Richmond Agitation Sedation Scale score and without sedation, we followed 1338 (81%) participants longitudinally for 18,645 ICU days. Deep sedation was present in 98% of participants at some point of the study and in 12,942 ICU days. Deep sedation was associated with higher mortality (interquartile odds ratio (OR) = 5.42, 4.23–6.95; p  < 0.001) and a significant decrease in ventilator (− 7.27; p  < 0.001), ICU (− 4.38; p  < 0.001), and hospital (− 7.00; p  < 0.001) free days. Agitation was also associated with higher mortality (OR = 39.9, 6.53–243, p  < 0.001). The most commonly used sedatives were opioids and benzodiazepines (9259 and 8453 patient days respectively), and the latter were associated with a 41% higher mortality in participants with a higher cumulative dose (75th vs 25th percentile, interquartile OR = 1.41, 1.12–1.77; p  < 0.01). The overall cumulative dose of benzodiazepines and opioids was high, 774.5 mg and 16.8 g, respectively, by day 7 and by day 28; these doses approximately doubled. Haloperidol was only used in 3% of ICU days; however, the use of it was associated with a 70% lower mortality (interquartile OR = 0.3, 0.22–0.44, p  < 0.001). Conclusions Deep sedation, agitation, and cumulative dose of benzodiazepines were all independently associated with higher 90-day mortality. Additionally, deep sedation was associated with less ventilator-, ICU-, and hospital-free days. In contrast, haloperidol was associated with lower mortality in our study.

In many countries, the combination of propofol and opioid is used as the preferred sedative regime during ERCP. However, the most serious risks of propofol sedation are oxygen deficiency and hypotension. Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, and to achieve widespread acceptance for procedural sedation, remimazolam must replace propofol which is the most commonly used for procedural sedation. The objective of this study was to compare the safety and efficacy profiles of the remimazolam and propofol when combined with alfentanil for sedation during ERCP procedures. A randomized, controlled, single-center trial. The Endoscopic Centre of Tianjin Nankai Hospital, China. 518 patients undergoing elective ERCP under deep sedation. Patients scheduled for ERCP were randomly assigned to be sedated with either a combination of remimazolam-alfentanil or propofol-alfentanil. The primary outcome was the prevalence of hypoxia, which was defined as SpO2 < 90% for >10 s. Other outcomes were the need for airway maneuver, procedure, and sedation-related outcomes and side effects (e.g., nausea, vomiting, and cardiovascular adverse events). A total of 518 patients underwent randomization. Of these, 250 were assigned to the remimazolam group and 255 to the propofol group. During ERCP, 9.6% of patients in the remimazolam group showed hypoxia, while in the propofol group, 15.7% showed hypoxia (p = 0.04). The need for airway maneuvering due to hypoxia was significantly greater in the propofol group (p = 0.04). Furthermore, patients sedated with remimazolam had a lower percentage of hypotension than patients sedated with propofol (p < 0.001). Patients receiving remimazolam sedation expressed higher satisfaction scores and were recommended the same sedation for the next ERCP. The procedure time in the remimazolam group was much longer than in the propofol group due to the complexity of the patient's disease, which resulted in a longer sedation time. During elective ERCP, patients administered with remimazolam showed fewer respiratory depression events under deep sedation with hemodynamic advantages over propofol when administered in combination with alfentanil. •The combination of propofol and an opioid is the preferred sedative regime during ERCP.•The major concerns with propofol sedation include oxygen desaturation and hypotension.•Patients administered with remimazolam showed fewer respiratory depression events and hemodynamic advantages over propofol.•These results may provide more options for ERCP sedation.

Propofol is a commonly utilized anesthetic for painless colonoscopy, but its usage is occasionally limited due to its potential side effects, including cardiopulmonary suppression and injection pain. To address this limitation, the novel compound ciprofol has been proposed as a possible alternative for propofol. This study sought to determine whether there are any differences in the safety and efficacy of propofol and ciprofol for painless colonoscopy. Randomized clinical trial. Single-centre, class A tertiary hospital, November 2021 to November 2022. Adult, American Society of Anesthesiologists Physical Status I to II and body mass index of 18 to 30 kg m−2 patients scheduled to undergo colonoscopy. Consecutive patients were randomly allocated in a 1:1 ratio to receive sedation for colonoscopy with ciprofol (group C) or propofol (group P). The primary outcome was the success rate of colonoscopy. The secondary outcomes were onset time of sedation, operation time, recovery time and discharge time, patients and endoscopists satisfaction, side effects (e.g. injection pain, myoclonus, drowsiness, dizziness, procedure recall, nausea and vomiting) and incidence rate of cardiopulmonary adverse events. No significant difference was found in the success rate of colonoscopy between the two groups (ciprofol 96.3% vs. propofol 97.6%; mean difference − 1.2%, 95% CI: −6.5% to 4.0%, P = 0.650). However, group C showed prolonged sedation (63.4 vs. 54.8 s, P < 0.001) and fully alert times (9 vs 8 min, P = 0.013), as well as reduced incidences of injection pain (0 vs. 40.2%, P < 0.001), respiratory depression (2.4% vs. 13.4%, P = 0.021) and hypotension (65.9% vs. 80.5%, P = 0.034). Patients satisfaction was also higher in Group C (10 vs 9, P < 0.001). Ciprofol can be used independently for colonoscopy. When comparing the sedation efficacy of ciprofol and propofol, a 0.4 mg kg−1 dose of ciprofol proved to be equal to a 2.0 mg kg−1 dose of propofol, with fewer side effects and greater patient satisfaction during the procedure. •Compared to the combination of ciprofol and opioids, ciprofol alone can still achieve a high success rates of colonoscopy.•Both are similar in efficacy, but ciprofol has a higher safety profile that making it more suitable for colonoscopy.•Less side effects and higher patient satisfaction of ciprofol compared with propofol.

Fospropofol disodium is a propofol prodrug that is water-soluble and has a reduced risk of bacterial contamination and hypertriglyceridemia compared with propofol. Prior to implementing a large randomized trial, we investigated the feasibility, initial efficacy, and safety of fospropofol disodium compared with propofol in long-term mild-to-moderate sedation in intensive care units (ICUs). Single-centered, prospective, unblind, randomized, parallel-group clinical trial. The general ICU of university-affiliated teaching hospital. Adult patients (n = 60) expected to have mechanical ventilation for >24 h were enrolled and randomly assigned to the fospropofol or propofol group. Interventions: The fospropofol group received continuous fospropofol disodium infusions and the propofol group received continuous propofol infusions. The sedation goal was a score of −3 to 0 on the Richmond Agitation and Sedation Scale (RASS). The primary outcome was the percentage of time spent in the target sedation range without rescue sedation. Safety outcomes were based on adverse events. Blood samples were collected to measure formate concentration in plasma. The median dose was 4.33 (IQR, 3.08–4.94) mg/kg/h in the fospropofol group and 1.96 (IQR, 1.44–2.94) mg/kg/h in the propofol group. The median percentage of time spent in the target RASS range without rescue sedation was identical in both groups, with 83.33% (IQR, 74.43%–100.00%) in the fospropofol group and 83.33% (IQR, 77.45%–100.00%) in the propofol group (p = 0.887). At least one adverse event was identifed in 23 (76.7%) fospropofol patients and 27 (90.0%) propofol patients. The most common adverse events were tachycardia and hypotension. No paresthesia, catheter-related bloodstream infection or propofol infusion syndrome in both groups was reported. Three patients in the fospropofol group had mild hypertriglyceridemia, and nine patients in propofol group had hypertriglyceridemia (mild in eight patients and moderate in one patient) (10% versus 30%, p = 0.104). The formate concentration in plasma was very low, and no significant difference was identified at any time point between the two groups. Fospropofol disodium appears to be a feasible, effective and safe sedative for patients receiving invasive mechanical ventilation with long-term sedation. •Both fospropofol disodium and propofol can provide adequate sedation in ICU patients with mechanical ventilation.•Fospropofol disodium had a comparable safety profile to that of propofol.•The formate concentration in plasma was very low, and no significant difference was identified at any time point between the 2 groups.

To determine whether limiting intraoperative sedation depth during spinal anesthesia for hip fracture repair in elderly patients can decrease the prevalence of postoperative delirium. We performed a double-blind, randomized controlled trial at an academic medical center of elderly patients (≥65 years) without preoperative delirium or severe dementia who underwent hip fracture repair under spinal anesthesia with propofol sedation. Sedation depth was titrated using processed electroencephalography with the bispectral index (BIS), and patients were randomized to receive either deep (BIS, approximately 50) or light (BIS, ≥80) sedation. Postoperative delirium was assessed as defined by Diagnostic and Statistical Manual of Mental Disorders (Third Edition Revised) criteria using the Confusion Assessment Method beginning at any time from the second day after surgery. From April 2, 2005, through October 30, 2008, a total of 114 patients were randomized. The prevalence of postoperative delirium was significantly lower in the light sedation group (11/57 [19%] vs 23/57 [40%] in the deep sedation group; P=.02), indicating that 1 incident of delirium will be prevented for every 4.7 patients treated with light sedation. The mean ± SD number of days of delirium during hospitalization was lower in the light sedation group than in the deep sedation group (0.5±1.5 days vs 1.4±4.0 days; P=.01). The use of light propofol sedation decreased the prevalence of postoperative delirium by 50% compared with deep sedation. Limiting depth of sedation during spinal anesthesia is a simple, safe, and cost-effective intervention for preventing postoperative delirium in elderly patients that could be widely and readily adopted. Trial Registration: www.clinicaltrials.gov Identifier: NCT00590707