Adjunctive Atropine Is Unnecessary during Ketamine Sedation in Children

Background:  The prophylactic coadministration of atropine or other anticholinergics during dissociative sedation has historically been considered mandatory to mitigate ketamine-associated hypersalivation. Emergency physicians (EPs) are known to omit this adjunct, so a prospective study to describe the safety profile of this practice was initiated.
Objectives:  To quantify the magnitude of excessive salivation, describe interventions for hypersalivation, and describe any associated airway complications.
Methods:  In this prospective observational study of emergency department (ED) pediatric patients receiving dissociative sedation, treating physicians rated excessive salivation on a 100-mm visual analog scale and recorded the frequency and nature of airway complications and interventions for hypersalivation.
Results:  Of 1,090 ketamine sedations during the 3-year study period, 947 (86.9%) were performed without adjunctive atropine. Treating physicians assigned the majority (92%) of these subjects salivation visual analog scale ratings of 0 mm, i.e., "none," and only 1.3% of ratings were ≥ 50 mm. Transient airway complications occurred in 3.2%, with just one (brief desaturation) felt related to hypersalivation (incidence 0.11%, 95% confidence interval = 0.003% to 0.59%). Interventions for hypersalivation (most commonly suctioning) occurred in 4.2%, with no occurrences of assisted ventilation or intubation.
Conclusions:  When adjunctive atropine is omitted during ketamine sedation in children, excessive salivation is uncommon, and associated airway complications are rare. Anticholinergic prophylaxis is not routinely necessary in this setting.     

Pediatric Liver Ultrasound Elastography

Ultrasound elastography is an easy, relatively affordable, noninvasive method that can be used to assess for hepatic fibrosis. The aim of this article is to present an introduction to ultrasound elastography and provide case examples to show when its use can be beneficial.     

Mild cognitive impairment: potential pharmacological treatment options

Both mild cognitive impairment and age-associated memory impairment are terms used to describe memory decline in otherwise healthy, intellectually intact individuals aged older than 50 years. It is estimated that up to 38% of the middle-aged and older population fulfill diagnostic criteria for this condition. Although the memory deficits observed in these individuals are fairly mild, they can interfere with day-to-day functioning. This article presents a review of the types of memory decline observed in older people, the diagnostic criteria used to define memory decline, the physiological and morphological brain changes that accompany aging, and the potential pharmacological treatment options, focusing on agents that have been evaluated in mildly cognitively impaired or normal older populations.     

Ticagrelor and the Prevention of Microvascular Complications in Diabetes Patients with Lower Extremity Arterial Disease; Rationale and Design of the Hema-Kinesis Trial

Background

Lower extremity arterial disease (LEAD) occurs more common in patients with diabetes than without diabetes. Microvascular complications of diabetes contribute to higher rates of adverse limb events in patients with LEAD. Blood flow in the macrocirculation and microcirculation is reduced with increasing low-shear and high-shear blood viscosity. We hypothesize that the adenosine enhancing properties of ticagrelor will reduce low-shear blood viscosity and improve microcirculatory flow in the dorsum of the feet of patients with type 2 diabetes. Ticagrelor is a P2Y12 receptor antagonist with evidence of cardiovascular event reduction in patients with acute coronary syndromes and those with a previous myocardial infarction. In a large multicenter trial of patients with symptomatic LEAD and a history of limb revascularization, ticagrelor was no more effective than clopidogrel in reducing cardiovascular disease events; however, this trial was not designed to investigate microvascular complications of diabetes.

Design

Hema-kinesis will evaluate whether ticagrelor monotherapy or ticagrelor combined with aspirin as compared with aspirin monotherapy can reduce blood viscosity-dependent blood flow in the feet of type 2 diabetes patients with LEAD. Eligible study participants will be randomized into a three-arm double-dummy crossover trial design. All subjects will have baseline blood viscosity measurements and determinations of microvascular flow using laser Doppler flowmetry.

Summary

If the results of Hema-kinesis are positive, ticagrelor should be considered as treatment to reduce microvascular complications of LEAD in patients with type 2 diabetes.

     

Continuous hypothalamic KATP activation blunts glucose counter-regulation in vivo in rats and suppresses KATP conductance in vitro

Aims/hypothesis

Acute systemic delivery of the sulfonylurea receptor (SUR)-1-specific ATP-sensitive K⁺ channel (K_ATP) opener, NN414, has been reported to amplify glucose counter-regulatory responses (CRRs) in rats exposed to hypoglycaemia. Thus, we determined whether continuous NN414 could prevent hypoglycaemia-induced defective counter-regulation.

Methods

Chronically catheterised male Sprague–Dawley rats received a continuous infusion of NN414 into the third ventricle for 8 days after implantation of osmotic minipumps. Counter-regulation was examined by hyperinsulinaemic–hypoglycaemic clamp on day 8 after three episodes of insulin-induced hypoglycaemia (recurrent hypoglycaemia [RH]) on days 5, 6 and 7. In a subset of rats exposed to RH, NN414 infusion was terminated on day 7 to wash out NN414 before examination of counter-regulation on day 8. To determine whether continuous NN414 exposure altered K_ATP function, we used the hypothalamic glucose-sensing GT1-7 cell line, which expresses the SUR-1-containing K_ATP channel.

Results

Continuous exposure to NN414 in the setting of RH increased, rather than decreased, the glucose infusion rate (GIR), as exemplified by attenuated adrenaline (epinephrine) secretion. Termination of NN414 on day 7 with subsequent washout for 24 h partially diminished the GIR. The same duration of exposure of GT1-7 cells to NN414 substantially reduced K_ATP conductance, which was also reversed on washout of the agonist. The suppression of K_ATP current was not associated with reduced channel subunit mRNA or protein levels.

Conclusions/interpretation

These data indicate that continuous K_ATP activation results in suppressed CRRs to hypoglycaemia in vivo, which in vitro is associated with the reversible conversion of K_ATP into a stable inactive state.     

Do sensor glucose levels accurately predict plasma glucose concentrations during hypoglycemia and hyperinsulinemia?

OBJECTIVE: The MiniMed Continuous Glucose Monitoring System (CGMS) measures subcutaneous interstitial glucose levels that are calibrated against three or more fingerstick glucose levels daily. The objective of the present study was to examine whether the relationship between plasma and interstitial fluid glucose is altered by changes in plasma glucose and insulin levels and how such alterations might influence CGMS performance. RESEARCH DESIGN AND METHODS: Arterialized plasma glucose, sensor glucose, and interstitial fluid glucose were measured by microdialysis in 11 healthy subjects during a 1.0 mU. kg(-1). min(-1) stepped euglycemic-hypoglycemic-hyperglycemic (plasma glucose approximately 5, 3.1, and 8.6 mmol/l, respectively) insulin clamp that raised plasma insulin to approximately 360-390 pmol/l. RESULTS: When the CGMS was calibrated versus plasma glucose levels before insulin infusion, basal sensor and plasma glucose were similar (5.0 +/- 0.3 vs. 5.2 +/- 0.3 mmol/l, respectively); dialysate glucose was 3.3 +/- 0.9 mmol/l. During the hyperinsulinemic-euglycemia study (plasma glucose 4.9 +/- 0.3 mmol/l), dialysate glucose fell by 30-35%, accompanied by a significant reduction in sensor glucose (to 3.7 +/- 0.6 mmol/l; P < 0.001 vs. plasma). Subsequently, sensor levels remained lower than plasma values during mild hypoglycemia (2.5 +/- 0.6 vs. 3.1 +/- 0.3 mmol/l; P < 0.01) and during recovery from hypoglycemia (7.3 +/- 1.2 vs. 8.6 +/- 0.6; P < 0.01). However, when the CGMS was calibrated against plasma glucose levels before and during each step of the clamp, sensor glucose levels increased throughout the study and did not differ from plasma glucose values during hypoglycemia. CONCLUSIONS: Although hyperinsulinemia may contribute to modest discrepancies between plasma and sensor glucose levels, the CGMS is able to accurately track acute changes in plasma glucose when calibrated across a range of plasma glucose and insulin levels.     

Involvement of corneal nerves in the progression of keratoconus

Keratoconus is a debilitating corneal thinning disease that principally develops in the second and third decades of life. Our group previously developed a novel approach to studying keratoconus, based on the observation that there is a gradient of damage across the keratoconic cone.We identified a number of cellular characteristics of keratoconus such as discrete incursions of fine cellular processes from the anterior keratocytes in association with localised indentation of the basal epithelium, and increased levels of the lysosomal enzymes Cathepsin B and G in aberrant keratocytes, located beneath compromised regions of Bowman's layer, but also deeper in the stroma. Enzyme activity by these cells seemed to be causing localised structural degradation of the anterior stroma, leading to near-complete destruction of both Bowman's layer and the stroma, often necessitating a full-thickness corneal graft for sight restoration.This current study extends our initial findings by investigating the role of corneal nerves passing between the stroma and epithelium at the sites of early degradative change observed previously, and may be facilitating the keratocyte-epithelial interactions in this disease.Cells in sections of normal and keratoconic human corneas were labelled with the fixable fluorescent viability dye 5-chloromethylfluorescein diacetate, antibodies to alpha-tubulin (nerves), alpha3beta1 integrin, Cathepsin B and G, and the nuclear dye DAPI, and then examined with a confocal microscope. Anterior keratocyte nuclei were seen wrapping around the nerves as they passed through the otherwise acellular Bowman's layer, and as the disease progressed and Bowman's layer degraded, these keratocytes were seen to express higher levels of Cathepsin B and G, and become displaced anteriorly into to the epithelium. Localised nerve thickenings also developed within the epithelium in association with Cathepsin B and G expression, and appeared to be very destructive to the cornea.Insight into the molecular mechanisms of keratoconic disease pathogenesis and progression can be gained from the process of extracellular matrix remodelling known from studies of connective tissues other than the cornea, and wound healing studies in the cornea. Further studies are required to determine how well this model fits the actual molecular basis of the pathogenesis of keratoconus.