Hypotension during propofol sedation for colonoscopy:an exploratory analysis

BACKGROUND: Intraoperative and postoperative hypotension occur commonly and are associated with organ injury and poor outcomes. Changes in arterial blood pressure (BP) during procedural sedation are not well described. METHODS: Individual patient data from five trials of propofol sedation for colonoscopy and a clinical database were pooled and explored with logistic and linear regression. A literature search and focused meta-analysis compared the incidence of hypotension with propofol and alternative forms of procedural sedation. Hypotensive episodes were characterised by the original authors' definitions (typically systolic BP 5 min, and in 89 (23%) the episodes exceeded 10 min. Meta-analysis of 18 RCTs identified an increased risk ratio for the development of hypotension in procedures where propofol was used compared with the use of etomidate (two studies; n=260; risk ratio [RR] 2.0 [95% confidence interval: 1.37–2.92]; P=0.0003), remimazolam (one study; n=384; RR 2.15 [1.61–2.87]; P=0.0001), midazolam (14 studies; n=2218; RR 1.46 [1.18–1.79]; P=0.0004), or all benzodiazepines (15 studies; n=2602; 1.67 [1.41–1.98]; P<0.00001). Hypotension was less likely with propofol than with dexmedetomidine (one study; n=60; RR 0.24 [0.09–0.62]; P=0.003). CONCLUSIONS: Hypotension is common during propofol sedation for colonoscopy and of a magnitude and duration associated with harm in surgical patients

What's New in Intravenous Anaesthesia?:New Hypnotics, New Models and New Applications

New anaesthetic drugs and new methods to administer anaesthetic drugs are continually becoming available, and the development of new PK-PD models furthers the possibilities of using arget controlled infusion (TCI) for anaesthesia. Additionally, new applications of existing anaesthetic drugs are being investigated. This review describes the current situation of anaesthetic drug development and methods of administration, and what can be expected in the near future

Intranasal dexmedetomidine in elderly subjects with or without beta blockade:a randomised double-blind single-ascending-dose cohort study

BACKGROUND: The aim of this double-blind, placebo-controlled, single-ascending-dose study was to determine the safety and tolerability of intranasal dexmedetomidine in the elderly.; METHODS: We randomly assigned 48 surgical patients ≥ ¥65 yr of age to receive single intranasal doses of dexmedetomidine or placebo (5:1 ratio) in four sequential dose cohorts: 0.5, 1.0, 1.5, and 2.0 mug kg-1. Each dose cohort comprised two groups of six subjects: a group of subjects using beta-blockers and a group not taking beta-blockers. Vital signs and sedation depth (Modified Observer's Assessment of Alertness and Sedation [MOAA/S] and bispectral index) were measured for 2 h after administration. Blood samples were taken to determine dexmedetomidine plasma concentrations.; RESULTS: One subject (1.0 mug kg-1) had acute hypotension requiring ephedrine. Systolic arterial BP decreased >30% in 15 of 40 subjects (37.5%) receiving dexmedetomidine, lasting longer than 5 min in 11 subjects (27.5%). The MAP decreased >30% (>5 min) in 10%, 20%, 50%, and 30% of subjects receiving dexmedetomidine 0.5, 1.0, 1.5, and 2.0 mug kg-1, respectively, irrespective of beta-blocker use. HR decreased 10-26%. MOAA/S score ≤ 3 occurred in 18 (45%) subjects; eight (20%) subjects receiving dexmedetomidine showed no signs of sedation. Tmax was 70 min. Cmax was between 0.15 ng ml-1 (0.5 mug kg-1) and 0.46 ng ml-1 (2.0 mug kg-1).; CONCLUSIONS: Intranasal dexmedetomidine in elderly subjects had a sedative effect, but caused a high incidence of profound and sustained hypotension irrespective of beta-blocker use. The technique is unsuitable for routine clinical use.; CLINICAL TRIAL REGISTRATION: NTR5513 (The Netherlands Trial Registry 5513)

Clinical Pharmacokinetics and Pharmacodynamics of Dexmedetomidine

Dexmedetomidine is an alpha(2)-adrenoceptor agonist with sedative, anxiolytic, sympatholytic, and analgesic-sparing effects, and minimal depression of respiratory function. It is potent and highly selective for alpha(2)-receptors with an alpha(2):alpha(1) ratio of 1620:1. Hemodynamic effects, which include transient hypertension, bradycardia, and hypotension, result from the drug's peripheral vasoconstrictive and sympatholytic properties. Dexmedetomidine exerts its hypnotic action through activation of central pre- and postsynaptic alpha(2)-receptors in the locus coeruleus, thereby inducting a state of unconsciousness similar to natural sleep, with the unique aspect that patients remain easily rousable and cooperative. Dexmedetomidine is rapidly distributed and is mainly hepatically metabolized into inactive metabolites by glucuronidation and hydroxylation. A high inter-individual variability in dexmedetomidine pharmacokinetics has been described, especially in the intensive care unit population. In recent years, multiple pharmacokinetic non-compartmental analyses as well as population pharmacokinetic studies have been performed. Body size, hepatic impairment, and presumably plasma albumin and cardiac output have a significant impact on dexmedetomidine pharmacokinetics. Results regarding other covariates remain inconclusive and warrant further research. Although initially approved for intravenous use for up to 24 h in the adult intensive care unit population only, applications of dexmedetomidine in clinical practice have been widened over the past few years. Procedural sedation with dexmedetomidine was additionally approved by the US Food and Drug Administration in 2003 and dexmedetomidine has appeared useful in multiple off-label applications such as pediatric sedation, intranasal or buccal administration, and use as an adjuvant to local analgesia techniques

Intranasal midazolam for the sedation of geriatric patients with care-resistant behaviour during essential dental treatment: An observational study

Objectives To describe the efficacy and safety of intranasal midazolam for sedation during essential dental treatment of geriatric patients with major neurocognitive disorder (MND) and care-resistant behaviour (CRB). Background Dental treatment is often impossible in geriatric MND patients with CRB. Intranasal midazolam may provide a non-invasive sedation method, but there is currently no information on its use in geriatric patients. Methods In this observational study, we included geriatric patients with severe MND and CRB needing urgent dental treatment. Each patient received 5 mg midazolam intranasally. Agitation/sedation levels, heart rate, respiration rate and oxygen saturation were recorded at 5-minute intervals. Results Thirty two patients were included. Mean age was 84 (+/- 7) years. Mean (SD) time to treatment start was 13 (+/- 5) minutes, and mean time to maximum sedation 17 (+/- 11) minutes. Sedation was sufficient to enable dental treatment to be completed in 31 (97%) patients. Anxiolysis/light sedation occurred in 16 (50%) patients, and moderate to deep sedation occurred in 16 (50%) patients. No patients suffered from apnoea, although 3 patients required a chin-lift manoeuvre. Hypoxaemia occurred in 1 of these patients and in 2 other patients without airway obstruction. All patients recovered uneventfully. In a regression model, age, weight and other sedative medication use were found not to be associated with maximum sedation depth. Conclusions Of 5 mg intranasal midazolam facilitates treatment of geriatric patients with MND in the comfort of their own environment. More information is needed to guide titration to balance the desired sedation level and patient safety

Dexmedetomidine versus Midazolam in Procedural Sedation: A Systematic Review of Efficacy and Safety

Objectives To systematically review the literature comparing the efficacy and safety of dexmedetomidine and midazolam when used for procedural sedation. Materials and Methods We searched MEDLINE, EMBASE and COCHRANE for clinical trials comparing dexmedetomidine and midazolam for procedural sedation up to June 20, 2016. Inclusion criteria: clinical trial, human subjects, adult subjects (>= 18 years), article written in English, German, French or Dutch, use of study medication for conscious sedation and at least one group receiving dexmedetomidine and one group receiving midazolam. Exclusion criteria: patients in intensive care, pediatric subjects and per protocol use of additional sedative medication other than rescue medication. Outcome measures for efficacy comparison were patient and clinician satisfaction scores and pain scores; outcome measures for safety comparison were hypotension, hypoxia, and circulatory and respiratory complications. Results We identified 89 papers, of which 12 satisfied the inclusion and exclusion criteria; 883 patients were included in these studies. Dexmedetomidine was associated with higher patient and operator satisfaction than midazolam. Patients receiving dexmedetomidine experienced less pain and had lower analgesic requirements. Respiratory and hemodynamic safety were similar. Conclusions Dexmedetomidine is a promising alternative to midazolam for use in procedural sedation. Dexmedetomidine provides more comfort during the procedure for the patient and clinician. If carefully titrated, the safety profiles are similar