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BACKGROUND: Propofol is a sedative-hypnotic with a rapid onset of action. There are only limited data evaluating propofol for flexible bronchoscopy. We analysed the feasibility and safety of propofol for bronchoscopy in a high output tertiary care centre. METHODS: Prospective data on patients undergoing flexible bronchoscopy at the University Hospital Basel, Switzerland, were analysed. Patient demographics, ASA class, Mallampati class, indication for bronchoscopy, bronchoscopic procedures, duration of examination, medication requirements, minor and major adverse events, haemodynamic parameters, as well as cough scores during the procedure were documented. Patients were followed up to discharge from the bronchoscopy suite. RESULTS: Data from 440 patients with a mean age 60 years (±15.5, 260 male) were analysed. The main indication for bronchoscopy was a suspicion of malignancy. The most common diagnostic procedures were bronchoalveolar lavage in 253 cases (31.5%) and bronchial washing in 174 cases (21.7%). The mean duration of the procedure was 19.6 min (±12.08). The mean propofol dose was 200 mg (±107.5) corresponding to 2.89 mg/kg (±1.70). Minor adverse events included oxygen desaturation in 72 (16.4%), hypotension in 68 (15.4%) and minor bleeding in 11 (2.5%) patients. No major adverse events were recorded. The median decline in systolic blood pressure after initiation of sedation was 14 mm Hg (3–28). A drop in systolic blood pressure greater than 20 mm Hg was observed in 166 of the 440 patients (37%). CONCLUSION: Propofol sedation for flexible bronchoscopy is feasible and safe.

A morpholine-based nucleotide analog was developed as a building block for hepatic siRNA targeting and stabilization. Attachment of an asialoglycoprotein-binding GalNAc ligand at the morpholine nitrogen was realized with different linkers. The obtained morpholino GalNAc scaffolds were coupled to the sense strand of a transthyretin-targeting siRNA and tested for their knockdown potency in vitro and in vivo . A clear structure-activity relationship was developed with regard to the linker type and length as well as the attachment site of the morpholino GalNAc moieties at the siRNA sense strand. Further, simple alkylation of the morpholine nitrogen led to a nucleotide analog, which increased siRNA stability, when used as a double 3'-overhang at the sense strand sequence. Combination of the best morpholino GalNAc building blocks as targeting nucleotides with an optimized stabilizing alkyl-substituted morpholine as 3'-overhangs resulted in siRNAs without any phosphorothioate stabilization in the sense strand and clearly improved the duration of action in vivo .

Background: Obstructive sleep apnea (OSA) is characterized by repetitive episodes of complete or partial obstruction of the upper airways during sleep. Conscious sedation for flexible bronchoscopy (FB) places patients in a sleep-like condition. We hypothesize that oxygen desaturation during flexible bronchoscopy may help to detect undiagnosed sleep apnea., Methods: Single-centre, investigator-initiated and driven study including consecutive patients undergoing FB for clinical indication. Patients completed the Epworth Sleepiness Scale (ESS), Lausanne NoSAS score, STOP-BANG questionnaire and the Berlin questionnaire and underwent polygraphy within 7 days of FB. FB was performed under conscious sedation with propofol. Oxygen desaturation during bronchoscopy was measured with continuous monitoring of peripheral oxygen saturation with ixTrend (ixellence GmbH, Germany)., Results: 145 patients were included in the study, 62% were male, and the average age was 65.8 ± 1.1 years. The vast majority of patients (n = 131, 90%) proved to fulfill OSA criteria based on polygraphy results: 52/131 patients (40%) had mild sleep apnea, 49/131 patients (37%) moderate sleep apnea and 30/131 patients (23%) severe sleep apnea. Patients with no oxygen desaturation had a significantly lower apnea-hypopnea index than patients with oxygen desaturation during bronchoscopy (AHI 11.94/h vs 21.02/h, p = 0.011). This association remained significant when adjusting for the duration of bronchoscopy and propofol dose (p = 0.023; 95% CI 1.382; 18.243) but did not hold when also adjusting for age and BMI., Conclusion: The severity of sleep apnea was associated to oxygen desaturation during flexible bronchoscopy under conscious sedation. Patients with oxygen desaturation during bronchoscopy might be considered for sleep apnea screening., Trial Registration: The Study was approved by the Ethics Committee northwest/central Switzerland, EKNZ (EK 16/13) and was carried out according to the Declaration of Helsinki and Good Clinical Practice guidelines. Due to its observational character, the study did not require registration at a clinical trial registry.

Bariatric surgery results in increased intestinal secretion of hormones GLP-1 and anorexigenic PYY, which is believed to contribute to the clinical efficacy associated with the procedure. This observation raises the question whether combination treatment with gut hormone analogs might recapitulate the efficacy and mitigate the significant risks associated with surgery. Despite PYY demonstrating excellent efficacy and safety profiles with regard to food intake reduction, weight loss, and glucose control in preclinical animal models, PYY-based therapeutic development remains challenging given a low serum stability and half-life for the native peptide. Here, combined peptide stapling and PEG-fatty acid conjugation affords potent PYY analogs with >14 h rat half-lives, which are expected to translate into a human half-life suitable for once-weekly dosing. Excellent efficacy in glucose control, food intake reduction, and weight loss for lead candidate 22 in combination with our previously reported long-acting GLP-1 analog is demonstrated in a diet-induced obesity mouse model.

The effects of oxytocin on food intake and body weight reduction have been demonstrated in both animal models and human clinical studies. Despite being efficacious, oxytocin is enzymatically unstable and thus considered to be unsuitable for long-term use in patients with obesity. Herein, a series of oxytocin derivatives were engineered through conjugation with fatty acid moieties that are known to exhibit high binding affinities to serum albumin. One analog ( OT-12 ) in particular was shown to be a potent full agonist at the oxytocin receptor (OTR) in vitro with good selectivity and long half-life (24 h) in mice. Furthermore, OT-12 is peripherally restricted, with very limited brain exposure (1/190 of the plasma level). In a diet-induced obesity mouse model, daily subcutaneous administration of OT-12 exhibited more potent anorexigenic and body weight reducing effects than carbetocin. Thus, our results suggest that the long-acting, peripherally restricted OTR agonist may offer potential therapeutic benefits for obesity.

Skeletal muscle myosin has potent procoagulant activity that is based on its ability to enhance thrombin generation due to binding coagulation factors Xa and Va and accelerating prothrombin activation. A well-studied myosin inhibitor that binds to myosin's neck region inhibits myosin-dependent prothrombin activation. Hence, to identify a potential binding site(s) on skeletal muscle myosin for factor Xa, 19 peptides (25-40 residues) representing the neck region, which consists of a regulatory light chain, an essential light chain, and a heavy chain (HC), were screened for inhibition of myosin-supported prothrombin activation. Peptide HC796-835 comprising residues 796-835 of the heavy chain strongly inhibited myosin-enhanced prothrombin activation by factors Xa and Va (50% inhibition at 1.2 μm), but it did not inhibit phospholipid vesicle-enhanced prothrombin activation. Peptide inhibition studies also implicated several myosin light chain sequences located near HC796-835 as potential procoagulant sites. A peptide comprising HC796-835's C-terminal half, but not a peptide comprising its N-terminal half, inhibited myosin-enhanced prothrombin activation (50% inhibition at 1.2 μm). This inhibitory peptide (HC816-837) did not inhibit phospholipid-enhanced prothrombin activation, indicating its specificity for inhibition of myosin-dependent procoagulant mechanisms. Binding studies showed that purified factor Xa was bound to immobilized peptides HC796-835 and HC816-837 with apparent K d values of 0.78 and 1.3 μm, respectively. In summary, these studies imply that HC residues 816-835 in the neck region of the skeletal muscle myosin directly bind factor Xa and, with contributions from light chain residues in this neck region, contribute to provision of myosin's procoagulant surface., (© 2019 Deguchi et al.)

Anorexigenic peptides offer promise as potential therapies targeting the escalating global obesity epidemic. Prolactin-releasing peptide (PrRP), a novel member of the RFamide family secreted by the hypothalamus, shows therapeutic potential by decreasing food intake and body weight in rodent models via GPR10 activation. Here we describe the design of a long-acting PrRP using our recently developed novel multiple ethylene glycol-fatty acid (MEG-FA) stapling platform. By incorporating serum albumin binding fatty acids onto a covalent side chain staple, we have generated a series of MEG-FA stapled PrRP analogs with enhanced serum stability and in vivo half-life. Our lead compound 18-S4 exhibits good in vitro potency and selectivity against GPR10, improved serum stability, and extended in vivo half-life (7.8 h) in mouse. Furthermore, 18-S4 demonstrates a potent body weight reduction effect in a diet-induced obesity (DIO) mouse model, representing a promising long-acting PrRP analog for further evaluation in the chronic obesity setting., Competing Interests: The authors declare no competing financial interest.

Peptide hormone relaxin-2, a member of the insulin family of peptides, plays a key role in hemodynamics and renal function and has shown preclinical efficacy in multiple disease models, including acute heart failure, fibrosis, preeclampsia, and corneal wound healing. Recently, serelaxin, a recombinant version of relaxin-2, has been studied in a large phase 3 clinical trial (RELAX-AHF-2) for acute decompensated heart failure patients with disappointing outcome. The poor in vivo half-life of relaxin-2 may have limited its therapeutic efficacy and long-term cardiovascular benefit. Herein, we have developed a semisynthetic methodology and generated potent, fatty acid-conjugated relaxin analogs with long-acting pharmacokinetic (PK) profile in rodents. The enhanced PK properties translated into improved and long-lasting pharmacodynamic effect in pubic ligament elongation (PLE) studies. The resultant novel relaxin analog, R9-13, represents the first long-acting relaxin-2 analog and could potentially improve the clinical efficacy and outcome for this important peptide hormone. This semisynthetic methodology could also be applied to other cysteine-rich peptides and proteins for half-life extension.

Oxytocin (OT) and its receptor (OT-R) are implicated in the etiology of autism spectrum disorders (ASD), and OT-R is a potential target for therapeutic intervention. Very few nonpeptide oxytocin agonists have currently been reported. Their molecular and in vivo pharmacology remain to be clarified, and none of them has been shown to be efficient in improving social interaction in animal models relevant to ASD. In an attempt to rationalize the design of centrally active nonpeptide full agonists, we studied in a systematic way the structural determinants of the affinity and efficacy of representative ligands of the V 1a and V 2 vasopressin receptor subtypes (V 1a -R and V 2 -R) and of the oxytocin receptor. Our results confirm the subtlety of the structure-affinity and structure-efficacy relationships around vasopressin/oxytocin receptor ligands and lead however to the first nonpeptide OT receptor agonist active in a mouse model of ASD after peripheral ip administration.

Fatty acid esters of hydroxylated fatty acids (FAHFAs) were discovered as a novel class of endogenous mammalian lipids whose profound effects on metabolism have been shown. In the current study, in vitro and in vivo the metabolic effects of two of these FAHFAs, namely palmitic acid-5- (or -9) -hydroxy-stearic acid (5- or 9-PAHSA, respectively) were profiled. In DIO mice fed with differentially composed low- or high-fat diets, acute and subchronic treatment with 5-PAHSA and 9-PAHSA alone, or in combination, did not significantly improve the deranged metabolic status. Neither racemic 5- or 9-PAHSA, nor the enantiomers were able to: (1) increase basal or insulin-stimulated glucose uptake in vitro, (2) stimulate GLP-1 release from GLUTag cells, or (3) induce GSIS in rat, mouse, or human islets or in a human pancreatic β cell line. Therefore, our data do not support the further development of PAHSAs or their derivatives for the control of insulin resistance and hyperglycemia., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Flexible bronchoscopy is increasingly used for diagnostic and therapeutic purposes. We aimed to examine the safety of flexible bronchoscopy with moderate sedation in patients with COPD., Methods: This study is a prospective, longitudinal, case-control, single-center study including 1,400 consecutive patients. After clinical and lung function assessments, patients were dichotomized in COPD or non-COPD groups. The primary end point was the combined incidence of complications., Results: The incidence of complications was similar in patients with and without COPD and independent of forced expiratory volume in the first second % predicted. Patients with COPD more frequently required insertion of a naso- or oropharyngeal airway; however, this difference was no longer significant after adjustment for age, gender, and duration of the procedure. Hypotension was significantly more common among patients with COPD. The number of episodes of hypoxemia ≤90% did not differ between the groups. However, patients with COPD had a lower mean and nadir transcutaneous oxygen saturation. Transcutaneous carbon dioxide tension (PtcCO 2 ) change over the time course was similar in both groups, but both peak PtcCO 2 and time on PtcCO 2 >45 mmHg were higher in the COPD group. There were no differences in patient-reported outcomes., Conclusion: The safety of flexible bronchoscopy is similar in patients with and without COPD. This finding confirms the suitability of the procedure for both clinical and research indications., Competing Interests: The authors report no conflicts of interest in this work.

The design and the synthesis of the first high-affinity fluorescent ligands for oxytocin receptor (OTR) are described. These compounds enabled the development of a TR-FRET based assay for OTR, readily amenable to high throughput screening. The validation of the assay was achieved by competition experiments with both peptide and nonpeptide OTR ligands as competitors. These probes represent the first selective fluorescent ligands for the oxytocin G protein-coupled receptor.

Propofol has been established as a reliable method for sedation in flexible bronchoscopy. There are no data comparing propofol administered as intravenous boluses versus continuous infusion. 702 consecutive patients undergoing flexible bronchoscopy were randomly allocated to receive intravenous propofol using either an intermittent bolus technique or a continuous infusion. The primary end-point was the number of adverse events assessed at the end of flexible bronchoscopy and at 24 h. The number of any adverse event was similar in both randomised groups (219 versus 211, p=0.810). There were complications in eight cases (seven major bleedings, one respiratory failure). As compared with the bolus group, the amount of propofol required was significantly higher in the infusion group (226 ± 147 mg versus 308 ± 204.8 mg, p<0.0001). In a multivariate regression model, this difference remained significant independent of the duration and the interventions performed during the procedure. The duration of bronchoscopy was significantly longer in the infusion group (median 14 (interquartile range 9-24) versus 17 (12-27) min, p<0.0001). Propofol continuous infusion is as safe as bolus administration; however, it is associated with higher propofol requirements and a longer duration of the bronchoscopy.

Background: Hypoxemia is a surrogate marker for periprocedural endoscopic complications. There are no data comparing the safety of propofol sedation with another sedative regimen in medical thoracoscopy., Objective: To evaluate whether sedation with propofol is as safe and effective as sedation with midazolam., Methods: Ninety consecutive patients undergoing medical thoracoscopy were randomly allocated to receive either intravenous propofol or midazolam. Predefined periprocedural complications included hypoxemia, hypotension, bleeding, need for airway insertion, mechanical ventilation, intensive care unit transfer and death. The primary endpoint was the mean lowest oxygen saturation during the procedure., Results: Randomized groups had similar demographics (64 ± 16 years, 57% male, 91% American Society of Anesthesiologists class III-IV) and a balanced distribution of procedures. The mean lowest oxygen saturation during the procedure was significantly lower in the propofol group as compared to the midazolam group (93 ± 6 vs. 96 ± 3%, p = 0.007). Patients randomized to propofol showed more episodes of hypoxemia (27 vs. 4%, p = 0.007) and hypotension (82 vs. 40%, p < 0.0001). No procedure had to be aborted. None of the patients required an artificial airway, mechanical ventilation or intensive care unit care, and none died., Conclusions: As assessed by the surrogate marker hypoxemia, propofol should not be considered the first choice for sedation in medical thoracoscopy.

An efficient solution-phase synthesis of aza-diketopiperazines (aza-DKP, triazinediones) is reported. A structurally diverse collection of c-[aza-alkylGly-Pro] derivatives and yet unreported 2,4,5-trisubstituted-1,2,4-triazine-3,6-diones has been synthesized starting from Fmoc-l-Pro-OH and various Fmoc-l-amino acids. To extend the practical value of this class of dipeptidomimetics, a general solid-phase synthesis approach amenable to library production was developed on both Wang-PS and HMBA-PS resins. The final acidic treatment of the resins in TFA/water mixture at room temperature enabled the rapid and quantitative cyclization/release highly pure triazinediones. The conformational preferences and the spatial organization of the three substituents of a representative 2,4,5-trisubstituted-1,2,4-triazine-3,6-dione were investigated by X-ray diffraction and (1)H NMR spectroscopy.

We have explored two divinylbenzene cross-linked polystyrene supports for use in a solid-supported N-terminal peptide tagging strategy. Resin-bound tags designed to be cleaved in a single step at the N-terminus of peptides have been devised and explored as peptide N-terminal tagging reagents (constructs) for subsequent mass spectrometric analysis. While the brominated tagging approach shows promise, the use of these specific solid supports has drawbacks, in terms of tagging reaction scale, for real applications in proteomics.

Objective: In November 2009, routine sampling of endoscopes performed to monitor the effectiveness of the endoscope-cleaning procedure at our hospital detected Pseudomonas aeruginosa. Herein we report the results of the subsequent investigation., Design and Methods: The investigation included environmental cultures for source investigation, molecular analysis by pulsed-field gel electrophoresis (PFGE) to reveal the identity of the strains, and determination of the bactericidal activity of the glutaraldehyde-based disinfectant used for automated endoscope reprocessing. In addition, patient outcome was analyzed by medical chart review, and incidence rates of clinical samples with P. aeruginosa were compared., Setting: The University Hospital of Basel is an 855-bed tertiary care center in Basel, Switzerland. Approximately 1,700 flexible bronchoscopic, 2,500 gastroscopic, 1,400 colonoscopic, 140 endoscopic retrograde cholangiopancreatographic, and 140 endosonographic procedures are performed annually., Results: P. aeruginosa was detected in samples obtained from endoscopes in November 2009 for the first time since the initiation of surveillance in 2006. It was found in the rinsing water and in the drain of 1 of the 2 automated endoscope reprocessors. PFGE revealed 2 distinct P. aeruginosa strains, one in each reprocessor. The glutaraldehyde-based disinfectant showed no activity against the 2 pseudo-outbreak strains when used in the recommended concentration under standard conditions. After medical chart review, 6 patients with lower respiratory tract and bloodstream infections were identified as having a possible epidemiological link to the pseudo-outbreak strain., Conclusions: This is the first description of a pseudo-outbreak caused by P. aeruginosa with reduced susceptibility to an aldehyde-based disinfectant routinely used in the automated processing of endoscopes.

Propofol and the combination of a benzodiazepine and an opiate have been established for sedation in flexible bronchoscopy. It is as yet unknown whether propofol in combination with an opiate is superior to propofol alone to suppress cough during the procedure. 300 consecutive patients undergoing flexible bronchoscopy at a tertiary care university hospital were randomly allocated to receive either the combination propofol and hydrocodone or propofol alone in a double-blind fashion. The primary end-point was the cough score during the procedure as estimated by the physician using a visual analogue scale. Demographics were similar in both groups. Compared with propofol alone, median (interquartile range) cough scores assessed by physicians, nurses and patients were significantly lower in the group randomised to the combination propofol and hydrocodone (2.5 (1.5-4.0) versus 2.0 (1.0-3.0), respectively, p=0.011). Additionally, patients receiving the combination required significantly lower doses of propofol than those receiving propofol alone (200 mg (140-280) versus 260 mg (180-350), p<0.0001). Complex examinations, including bronchoalveolar lavage or transbronchial biopsy, benefited more from additional opiate. The duration of the procedure, time to discharge and complication rate were similar in both groups. The combination of propofol and hydrocodone is safe and superior to propofol alone for cough suppression in flexible bronchoscopy.

Background: In contrast to asthma, the indication for bronchodilators prior to bronchoscopy in patients with COPD has not been properly investigated. We therefore performed a randomized, double-blind, placebo-controlled trial to determine whether use of a short-acting bronchodilator provides a protective effect in patients with COPD undergoing bronchoscopy., Methods: One hundred twenty patients undergoing bronchoscopy were included. Patients with COPD were randomized to receive either 200 mug of salbutamol (n = 40) or placebo (n = 40) before bronchoscopy. Control patients (n = 40) did not receive any inhaled medication. Spirometry was performed before and 2 h after bronchoscopy in all patients. Sedative drug requirements and hemodynamic parameters were recorded., Results: Hemodynamic findings before, during, and after bronchoscopy were similar in patients with COPD randomized to either salbutamol or placebo (p = not significant for all). Compared to prebronchoscopy values, postbronchoscopy percentage of predicted FEV(1) decreased significantly in all three groups: salbutamol (median, - 4.7%; interquartile range [IQR], - 13.3 to 6.6); placebo (median, - 4.8%; IQR, - 19.9 to 8.4); and control subjects (median, - 10.0%; IQR, - 20.2 to - 3.3) [p = 0.023]. The decrease in FEV(1) was similar in all three patient groups (p = 0.432). The relative change in FEV(1) was inversely correlated to the increasing severity of COPD as expressed by Global Initiative for Chronic Obstructive Lung Disease stages (p = 0.01)., Conclusions: Premedication with an inhaled short-acting beta-agonist cannot be recommended in patients with COPD undergoing bronchoscopy.

The aim of the present study was to assess the feasibility of measuring combined arterial oxygen saturation measured by pulse oximetry (Sp,O2) and cutaneous carbon dioxide tension (Pc,CO2) to monitor ventilation and quantify change in Pc,CO2 during bronchoscopy. Combined Sp,O2 and Pc,CO2 were measured at the ear lobe in 114 patients. In four patients, the ear-clip slipped and they were excluded. In total, 11 patients had artefacts with Sp,O2 recordings, thus, Sp,O2 was analysed in 99 patients. Spirometry data were available in 77 patients. Multivariate analysis of covariance and logistic regression were used for statistical analyses. Mean baseline Pc,CO2 was 4.78+/-1.06 kPa (36+/-8 mmHg) and mean rise in the Pc,CO2 during bronchoscopy was 1.26+/-0.70 kPa (9.5+/-5.3 mmHg), while mean Pc,CO2 at the end of bronchoscopy was 5.85+/-1.19 kPa (44+/-9 mmHg) . Baseline Pc,CO2 and the lowest Sp,O2 were significantly associated with peak Pc,CO2 and the change in Pc,CO2 during bronchoscopy. Risk of significant hypoxaemia (Sp,O2

Objective: Topical anesthesia for flexible bronchoscopy can be administered via transcricoid injection, nebulizer, or directly through the bronchoscope in a "spray as you go" fashion. We performed a prospective, randomized, double-blind, placebo-controlled trial to evaluate whether nebulized lidocaine provides additional benefit and reduces the total anesthetic dose required during bronchoscopy., Setting: Tertiary care university hospital., Methods: One hundred fifty patients (93 men; age, 20 to 89 years) undergoing diagnostic flexible bronchoscopy were randomized to receive either 4 mL of 4% lidocaine (160 mg) or 4 mL of saline solution as placebo via nebulization. Combined sedation was achieved using 5 mg of IV hydrocodone and midazolam boluses. Supplemental lidocaine doses and total midazolam required as judged by the bronchoscopist were recorded for each patient. After the procedure, both bronchoscopists and patients charted their perception of cough on a 10-cm visual analog scale (VAS). Similarly, patients recorded their discomfort related to the procedure on a 10-cm VAS., Results: The most common procedures were BAL in 77 cases (51%), transbronchial biopsy in 40 cases (27%), and transbronchial needle aspiration in 34 cases (23%). Outcome parameters, including hemodynamic findings, duration of the procedure, cough scores for physicians and patients, discomfort score for patients, midazolam doses, and supplemental lidocaine doses, were similar in both groups. Mean total lidocaine dose required in the lidocaine group was 318 +/- 41 mg and was significantly higher than the total dose required in the placebo group (157 +/- 44 mg [+/- SD]) [p < 0.001]., Conclusion: Additional nebulized lidocaine cannot be recommended for flexible bronchoscopy performed under combined sedation.

Objectives: Patient-controlled sedation (PCS) with propofol, is well tolerated and reduces recovery time and staff required during endoscopic interventions. "Who" administers the drug proves economically crucial. With the aim of maintaining safety, medical quality, and patient satisfaction, this study investigates PCS versus nurse-administered propofol sedation (NAPS) in a cohort of consecutive patients., Methods: One hundred and fourteen patients, aged 22-90 yr, undergoing only colonoscopy participated in this prospective randomized trial. Patients were randomly assigned to either PCS or NAPS. If patients declined randomization for different reasons of reluctance to PCS they were assigned to a standard nurse-sedated control group. All patients received pethidine presedation for analgesia. Visual analogue scales followed patient anxiety level, tolerability, pain, and satisfaction, and endoscopist's assessment of the procedure., Results: Given the choice, 35% of the patients who were rather younger and more anxious declined randomization to PCS. The mean total dose of propofol needed in this group was higher, but the patients had a tendency to rate the global tolerance and the pain of the examination as less comfortable compared to the two randomized groups. Self-administration of propofol created a significantly different drug profile and higher medication costs. With regard to the safety parameters there was no difference between PCS and NAPS. In their global assessments, the patients and endoscopists tended to prefer NAPS., Conclusions: Individual patient characteristics and attitudes toward self-control are crucial for PCS. While being a viable option for patients who are able and willing to handle, this technique is not applicable in a considerable portion of everyday patients.

Objectives: Propofol, a rapidly-acting hypnotic agent, is increasingly being used for endoscopic sedation. Serious adverse effects, including respiratory and cardiovascular depression, make many endoscopists reluctant to use propofol in critically ill patients. This study characterizes propofol's safety profile in consecutive high-risk patients (American Society of Anesthesiologists [ASA] classes III and IV) compared with matched subjects (ASA classes I and II)., Methods: During a 19-month period, 1370 at risk-patients were sedated with propofol, of whom 47% (614 ASA III, 28 ASA IV) were age matched with 642 consecutive patients of the same gender and age assigned to ASA classes I and II and undergoing the same endoscopic procedures (395 gastroscopies, 201 colonoscopies, 14 combined). Registered nurses performed all sedations by propofol dose titration while carefully monitoring arterial oxygen saturation, heart rate, and blood pressure., Results: No major complications occurred among the critically ill patients. There was, however, an increased risk for a short relevant oxygen desaturation (<90%) of 3.6% for ASA III and IV versus 1.7% for ASA I and II (p = 0.036). In four versus one case, short mask ventilation was necessary. Also, a greater proportion of patients showed a > or =5% oxygen saturation decrease. There was no pronounced influence on arterial pressure or heart rate and no perforations in 336 colonoscopies., Conclusions: With careful monitoring, propofol sedation during GI endoscopies is safe, even for high-risk patients. Considering their higher comorbidity and tendency toward oxygen desaturation, they need particularly careful monitoring, and the required dose is, on mean, 10-20% lower than in ASA classes I and II.

Aim: To characterize the safety of endoscopic procedures and propofol use as administered by nurses in a cohort of elderly patients., Methods: During 19 months all endoscopy patients > 70 years were eligible for this prospective observational study. Patients were assigned to group A (70-85 years) or group B (> 85 years). Records from all patients < 70 years treated during the same period served as controls. Specially trained nurses administered the propofol and monitored for complications (decrease in the peripheral oxygen saturation, mean arterial pressure or heart rate)., Results: There were 1435 endoscopic procedures in group A and 351 in group B. There was no procedure or sedation-related mortality, nor a significantly greater need for emergency intervention than in the control group. Two patients required short mask ventilation but recovered without sequelae. Compared with younger patients, there was a significant increase in risk for a short oxygen desaturation < 90% and a decrease in oxygen saturation > 5%. Arterial hypotension occurred significantly more often in the control group than among the aged patients., Conclusions: This present study documents that gastrointestinal endoscopic procedures are safe and well tolerated even in the very elderly. Nurse-administered propofol is a safe and reasonable sedation method in these patients.

Background: Conscious sedation is standard for GI endoscopy. Propofol increasingly is used as an alternative drug to avoid unwanted effects of the commonly used benzodiazepines. Although propofol in the hands of nonanesthesiologists is still controversial, this study characterized the safety profile of propofol administered by nurses under supervision of the gastroenterologist., Methods: All patients undergoing any endoscopic procedure between September 2000 and December 2001 in the gastroenterology department of an academic tertiary medical center were eligible for inclusion in this prospective observational study. Sedation was voluntary. Demographic data, type of endoscopic procedure, and clinical features were recorded. A structured personal history led to a 5-class risk stratification based on the criteria of the American Society of Anesthesiologists. A total of 3475 procedures were performed in 2574 patients using propofol administered by registered nurses., Results: No major complications occurred because of the use of propofol, but overall decreases in the mean values for oxygen saturation (-2%), arterial pressure (-18%), and pulse rate (-10%) were observed. Severe respiratory depression requiring intervention occurred in less than 0.3% of all patients given propofol., Conclusion: The administration of propofol by registered nurses, with careful monitoring under the supervision of the gastroenterologist, is safe for conscious sedation during GI endoscopic procedures.