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

First administration to man of Org 25435, an intravenous anaesthetic: A Phase 1 Clinical Trial

BACKGROUND: Org 25435 is a new water-soluble alpha-amino acid ester intravenous anaesthetic which proved satisfactory in animal studies. This study aimed to assess the safety, tolerability and efficacy of Org 25435 and to obtain preliminary pharmacodynamic and pharmacokinetic data. METHODS: In the Short Infusion study 8 healthy male volunteers received a 1 minute infusion of 0.25, 0.5, 1.0, or 2.0 mg/kg (n = 2 per group); a further 10 received 3.0 mg/kg (n = 5) or 4.0 mg/kg (n = 5). Following preliminary pharmacokinetic modelling 7 subjects received a titrated 30 minute Target Controlled Infusion (TCI), total dose 5.8-20 mg/kg. RESULTS: Within the Short Infusion study, all subjects were successfully anaesthetised at 3 and 4 mg/kg. Within the TCI study 5 subjects were anaesthetised and 2 showed signs of sedation. Org 25435 caused hypotension and tachycardia at doses over 2 mg/kg. Recovery from anaesthesia after a 30 min administration of Org 25435 was slow (13.7 min). Pharmacokinetic modelling suggests that the context sensitive half-time of Org 25435 is slightly shorter than that of propofol in infusions up to 20 minutes but progressively longer thereafter. CONCLUSIONS: Org 25435 is an effective intravenous anaesthetic in man at doses of 3 and 4 mg/kg given over 1 minute. Longer infusions can maintain anaesthesia but recovery is slow. Hypotension and tachycardia during anaesthesia and slow recovery of consciousness after cessation of drug administration suggest this compound has no advantages over currently available intravenous anaesthetics

Earliest rock fabric formed in the Solar System preserved in a chondrule rim

Rock fabrics – the preferred orientation of grains – provide a window into the history of rock formation, deformation and compaction. Chondritic meteorites are among the oldest materials in the Solar System1 and their fabrics should record a range of processes occurring in the nebula and in asteroids, but due to abundant fine-grained material these samples have largely resisted traditional in situ fabric analysis. Here we use high resolution electron backscatter diffraction to map the orientation of sub-micrometre grains in the Allende CV carbonaceous chondrite: the matrix material that is interstitial to the mm-sized spherical chondrules that give chondrites their name, and fine-grained rims which surround those chondrules. Although Allende matrix exhibits a bulk uniaxial fabric relating to a significant compressive event in the parent asteroid, we find that fine-grained rims preserve a spherically symmetric fabric centred on the chondrule. We define a method that quantitatively relates fabric intensity to net compression, and reconstruct an initial porosity for the rims of 70-80% - a value very close to model estimates for the earliest uncompacted aggregates2,3. We conclude that the chondrule rim textures formed in a nebula setting and may therefore be the first rock fabric to have formed in the Solar System