Midazolam as a sole sedative for computed tomography imaging in pediatric patients

Objective: To evaluate the efficacy and adverse effects of i.v. midazolam as a sole agent for sedation in children for computed tomography (CT) imaging. Materials and Methods: Prospective clinical trial in which 516 children under ASA classification II–IV (273 boys and 243 girls) in the age group of 6 months to 6 years for elective CT scan were enrolled over a 17‐month period. Patients were administered i.v. midazolam 0.2 mg·kg^?1 and further boluses of 0.1 mg·kg^?1 (total 0.5 mg·kg^?1) if required. Measurements included induction time, efficacy, side effects, complications, and degree of sedation. Sedation was graded on the basis of Ramsay sedation score (RSS) as over sedated (RSS 5–6), adequately sedated (AS, RSS 3–4), under sedated (RSS 1–2), or failed if the procedure could not be completed or another agent had to be administered. Results: Of the 516 procedures, 483 brains, 16 chests, and 17 abdomens were scanned with a mean duration of 4.75 ± 1.75 min with a mean dose of 0.212 mg·kg^?1 of i.v. midazolam. Four hundred and sixty‐five (90.12%) patients were AS in 5.9 ± 0.7 min while 40 (7.75%) patients required additional boluses. Of these 40 patients, 24 (4.65%) required a single bolus, 12 (2.32%) required two boluses, whereas the remaining four (0.78%) required three boluses. In 11 (2.13%; P < 0.0001) patients, the scan could not be completed satisfactorily. Side effects were seen in 46 (9.11%) patients in the form of desaturation, hiccups (seven patients, 1.38%), and agitation (four patients, 0.79%). Desaturation (SpO₂ 90–95%) was seen in 35 (6.93%) patients, which was corrected by topical application of oxygen. None of the patients exhibited any complications such as pulmonary aspiration or need to maintain airway. The patients were kept under observation for 1 h after the procedure. Conclusion: The level of sedation achieved in children with midazolam 0.2 mg·kg^?1 is adequate for imaging with minimal side effects, no airway complications, and fast recovery. It can be recommended as the sole agent for sedation in pediatric patients for CT imaging.     

Calculating the insulin to carbohydrate ratio using the hyperinsulinaemic-euglycaemic clamp-a novel use for a proven technique

BACKGROUND: In patients with type 1 diabetes, three main variables need to be assessed to optimize meal-related insulin boluses: pre-meal blood glucose (BG), insulin to carbohydrate ratio (I : C), and basal insulin. We are presenting data for a novel use of the hyperinsulinaemic-euglycaemic clamp (HEC) in patients with type 1 diabetes that minimizes the impact of these variables and can be used to determine the I : C. METHODS: Ten subjects (six men and four women) using continuous subcutaneous insulin infusion (CSII) pumps were recruited for this study [24-65 years; BMI 27.1 +/- 4.9 kg/m(2); A1C 7.2 +/- 1.4% (mean +/- SD)]. The HEC used a primed continuous intravenous insulin infusion of 40 mU/m(2)/min and a variable infusion of 20% glucose to maintain BG at 90 mg/dL. After subjects were in steady state (SS) for 50 min, a standardized meal (40% of total calories/day - 30% carbohydrate, 30% protein, 40% fat) was consumed. Subjects gave the insulin bolus with their CSII pump. No changes were made in the glucose infusion rate. RESULTS: Mean BG at SS was 85.7 +/- 10.4 mg/dL. Peak BG was 115.0 +/- 12.7 mg/dL at 68.5 +/- 8.8 min after the meal. Mean I : C was 1 : 9.3 +/- 1.7 (range 1 : 7-1 : 12). Insulin sensitivity varied from 1.9 to 9.1 mg/kg/min. CONCLUSIONS: The HEC can be used to reduce confounding factors and to determine the I : C. As a first estimate of the I : C in patients with type 1 diabetes, it is recommended to start with a ratio of 1 : 9.3 and to measure post-prandial BG at 70 min.     

Evaluation of a Solid Bolus Suitable for Esophageal Scintigraphy

This study was designed to select a suitable solid bolus for esophageal scintigraphy. Optimally, a bolus should leave minimal residual buccal and pharyngeal activity after being swallowed. We compared the oropharyngeal behavior of three boluses, i.e., omelette, egg white, and paté of 1- and 3-ml volume. Thirty patients without dysfunction of the upper esophageal sphincter were recruited for the study. Scintigraphy interpretation was based on the results of condensed images and time activity curves. A total of 108 oropharyngeal transits were analyzed. First we determined the most appropriate volume (1 or 3 ml) of paté, omelette, and egg white (i.e., the volume with the least residual oropharyngeal activity). Buccal or pharyngeal bolus retention occurred significantly less frequently with 1 ml paté than 3 ml (p = 0.03) and also less frequently with 3 ml egg white than with 1 ml egg white (p = 0.03), and the mean buccal bolus retention index was lower using 3 ml omelette than 1 ml omelette (p = 0.03). Then we identified the most suitable of the three selected boluses. Both oral and pharyngeal residues were higher for paté (1 ml) than for omelette (p = 0.02 and 0.05), and pharyngeal residue was significantly lower for omelette (3 ml) than for egg white (3 ml) (p = 0.02). In conclusion, a 3-ml bolus of radiolabeled omelette seems to be the most suitable bolus for exploration of esophageal transit, and its use could enhance the potential of scintigraphy in the assessment of esophageal disorders.     

Effect of bolus length of intraarterial injections on contrast-enhanced MR-angiography in patients

PURPOSE: To perform MR-guided interventions, repetitive injections of contrast agent in the arterial system are necessary. By reducing the intraarterial bolus length during image acquisition and consecutively reducing the gadolinium-chelate-based contrast agent dose, we focus on a comparable vascular depiction. The tradeoff in reducing bolus length is vascular depiction. MATERIALS AND METHODS: Intraarterial gadolinium-chelate injection was performed to depict the femoropopliteal artery and infrapopliteal arteries in six patients. Six measurements with a bolus length of 20% to 100% of the total acquisition time were performed (three-dimensional [3D] Turbo-fast low-angle shot (FLASH) sequence, 1.5 T). Contrast-to-noise ratio (CNR) was determined and a consensus reading of vascular depiction was performed. RESULTS: CNR values comparable 100% of bolus length were obtained for the femoropopliteal artery at >or=40% and for the infrapopliteal arteries at >or=60%. Qualitative analysis demonstrated that a bolus length of >or=60% is necessary to reveal a good diagnostic vascular depiction. CONCLUSION: Quantitatively, a reduction of intraarterial gadolinium-chelate dosage in patients is possible down to 40% in the femoropopliteal artery and to 60% in the infrapopliteal arteries to acquire a CNR comparable to 100% of bolus length. Qualitatively, however, the bolus length can only be reduced down to 60% for both level to produce a good diagnostic vascular depiction and is, for diagnostic purposes, the limiting factor.     

Dynamic MR imaging of the gastroesophageal junction in healthy volunteers during bolus passage

PURPOSE: To evaluate the feasibility of noninvasive dynamic fast magnetic resonance imaging (MRI) during swallowing in healthy volunteers, and to determine esophageal function at the gastroesophageal junction during swallowing. MATERIALS AND METHODS: A total of 20 healthy volunteers underwent MRI while swallowing in the supine position. Dynamic gradient-echo (GRE) sequences (balanced fast field echo [B-FFE]) were employed in three planes on a 1.5T unit using a phased-array body coil. Buttermilk spiked with gadolinium (Gd) chelate (40:1) for bolus passage was used as an oral contrast agent. We evaluated visualization of esophageal bolus transit, bolus transit time (BTT), peristalsis, identification of the gastroesophageal junction, and reflux during the Valsalva maneuver. RESULTS: The mean visible length of the esophagus was 16.2+/-5.3 cm in the sagittal view, and 13.8+/-4.9 cm in the coronal view. In the sagittal view the BTT was defined in 15 of 20 volunteers and was 7.6+/-1.4 seconds. The BTT in the coronal view was measured in seven of 20 volunteers and was 8+/-1.3 seconds on average. The axial view yielded higher scores (2.25) than the coronal (1.98) and sagittal (1.78) views for identification of the cardia and during the Valsalva maneuver. Bolus contrast was better displayed in the sagittal (2.2) view than in the coronal (2.08) or axial (1.73) planes. In six volunteers, gastroesophageal abnormalities, such as axial hernia, reflux, and nonperistaltic contractions, were identified. For statistical analysis we used the Friedman test and a one-way analysis of variance (ANOVA). CONCLUSION: The results indicate that dynamic MR swallowing is a feasible and reproducible technique that warrants further studies in patients.     

Insulin pump therapy in youth with type 1 diabetes: toward closed-loop systems

Introduction: Insulin pump technology has advanced considerably over the past three decades, leading to more favorable metabolic control and less hypoglycemic events when compared with multiple daily injection therapy. The use of insulin pumps is increasing, particularly in children and adolescents with type 1 diabetes.

Areas covered: This review outlines recent developments in insulin pump therapy from a pediatric perspective. ‘Smart’ pumps, sensor-augmented pump therapy and threshold-suspend feature of insulin pumps are reviewed in terms of efficacy, safety and psychosocial impact. The current status of closed-loop systems focusing on clinical outcomes is highlighted.

Expert opinion: Closed-loop insulin delivery is gradually progressing from bench to the clinical practice. Longer and larger studies in home settings are needed to expand on short- to medium-term outpatient evaluations. Predictive low glucose management and overnight closed-loop delivery may be the next applications to be implemented in daily routine. Further challenges include improvements of control algorithms, sensor accuracy, duration of insulin action, integration and size of devices and connectivity and usability. Gradual improvements and increasing sophistication of closed-loop components lie on the path toward unsupervised hands-off fully closed-loop system.     

Neurophysiological correlates of mental arithmetic

Thirteen subjects were extensively trained on nine multiplication problems varying in difficulty. Practice was associated with a reaction time speed up and an attenuation of the problem size effect. The introduction of previously unpracticed problems led to a performance rebound to pretraining levels, indicating practice specificity. The event-related potentials were characterized by a late positive complex, followed by a positive slow wave. Offset latency of positive slow wave and preresponse amplitude at parietal electrodes showed practice specificity effects that systematically changed with practice and problem size, indicating an association with the load imposed on working memory. The peak of the late positive complex probably reflects task learning or adaptation effects because it was attenuated by practice predominantly at frontal electrodes, showed no practice specificity, and was not affected by problem size.     

Partial volume effect (PVE) on the arterial input function (AIF) in T1‐weighted perfusion imaging and limitations of the multiplicative rescaling approach

The partial volume effect (PVE) on the arterial input function (AIF) remains a major obstacle to absolute quantification of cerebral blood flow (CBF) using MRI. This study evaluates the validity and performance of a commonly used multiplicative rescaling of the AIF to correct for the PVE. In a group of six patients, perfusion imaging was performed using a T₁‐weighted approach that minimizes confounding susceptibility artifacts. Various degrees of PVE were induced on the AIF and subsequently corrected using four different schemes of multiplicative AIF rescaling. Our results show that a multiplicative rescaling is not always applicable and can introduce a CBF bias. An easily measurable quantity denoted the tissue signal fraction (TSF) is proposed as a measure of the applicability of a multiplicative rescaling. For the present CBF quantification method, a TSF of <0.4 results in a CBF bias <15% after AIF rescaling. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Pharmacokinetics of apomorphine in parkinsonian patients

Summary— Apomorphine, a dopamine agonist, has been used efficiently in parkinsonian patients to treat severe levodopa-induced on-off phenomenon. Motor improvement has been obtained both with continuous subcutaneous (SC) infusions, and multiple SC injections. So as to assist in the understanding of the clinical results, we studied the peripheral pharmacokinetics of apomorphine in 20 patients after intravenous (IV) or SC injections in the anterior abdominal wall and in the thigh at various doses, or SC infusion. Plasma apomorphine levels were measured by high-performance liquid chromatography with electrochemical detection. After an SC injection in the abdominal wall, the T_max was brief (16 ± 11 min) the drug was rapidly cleared from the plasma and had a short plasma half-life (69.7 ± 25.8 min). The AUC was similar following SC and IV injections, suggesting that apomorphine was completely absorbed from subcutaneous tissue. Inter-subject variability in drug absorption was large. We noticed a trend towards a more complete absorption following injection in the abdominal wall rather than in the thigh. In patients chronically treated by continuous SC infusion, the apparent plasma half-life was five times longer than that following SC or IV injections. These pharmacokinetic data may explain the rapid onset and brief duration of clinical effects, and the usefulness of individual titration for intermittent SC apomorphine injections, and the smoother motor response obtained with continuous SC infusions.     

Influence of everyday bolus consistencies in different body positions on high‐resolution esophageal pressure topography (HREPT) parameters

The standard protocol for esophageal manometry involves placing the patient in the supine position with head turned to left (supine head left [SHL]) while evaluating liquid bolus swallows. Routinely, semisolid or solid boluses are not evaluated. Currently, the daily American diet includes up to 40% solid or semisolid texture. Thus far, the data on the effect of different bolus on high‐resolution esophageal pressure topography (HREPT) parameters are scarce. This study aims to evaluate the effect of every day bolus consistencies in different body positions on HREPT variables. HREPT was performed on healthy volunteers with a modified protocol including liquid swallows in the SHL position followed by applesauce (semisolid), cracker (solid), and marshmallow (soft solid) in three different positions (SHL, sitting, and standing). A total of 38 healthy adult subjects (22 males and 16 females, median age = 27, and mean body mass index = 25) were evaluated. The resting upper esophageal sphincter pressure was significantly different while subjects swallowed crackers, applesauce, and marshmallows in most positions compared with liquid SHL (P < 0.05). The lower esophageal sphincter, contractile front velocity, and distal contractile integral pressures did not differ in all different consistencies compared with SHL. The integrated relaxation period was significantly higher with solid bolus compared with liquid bolus only in SHL position. The intrabolus pressure was significantly different with solid and soft solid boluses in all postures compared to liquid SHL. The American diet consistency affects upper esophageal sphincter pressure and partially integrated relaxation period and intrabolus pressure in various positions. Semisolid bolus swallows do not cause substantial pressure changes and are safe for evaluation and maintaining adequate caloric intake in patients with dysphagia who cannot tolerate solids.