Differential expression of microRNAs following cardiopulmonary bypass in children with congenital heart diseases.

BACKGROUND: Children with congenital heart defects (CHDs) are at high risk for myocardial failure after operative procedures with cardiopulmonary bypass (CPB). Recent studies suggest that microRNAs (miRNA) are involved in the development of CHDs and myocardial failure. Therefore, the aim of this study was to determine alterations in the miRNA profile in heart tissue after cardiac surgery using CPB. METHODS: In total, 14 tissue samples from right atrium were collected from patients before and after connection of the CPB. SurePrint™ 8 × 60K Human v21 miRNA array and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were employed to determine the miRNA expression profile from three patients before and after connection of the CPB. Enrichment analyses of altered miRNA expression were predicted using bioinformatic tools. RESULTS: According to miRNA array, a total of 90 miRNAs were significantly altered including 29 miRNAs with increased and 61 miRNAs with decreased expression after de-connection of CPB (n = 3) compared to before CPB (n = 3). Seven miRNAs had been validated using RT-qPCR in an independent cohort of 11 patients. Enrichment analyses applying the KEGG database displayed the highest correlation for signaling pathways, cellular community, cardiovascular disease and circulatory system. CONCLUSION: Our result identified the overall changes of the miRNome in right atrium tissue of patients with CHDs after CPB. The differentially altered miRNAs lay a good foundation for further understanding of the molecular function of changed miRNAs in regulating CHDs and after CPB in particular.

Impact of intraoperatively salvaged and washed blood on stimulated cytokine release in vitro.

BACKGROUND: Intraoperative blood salvage and processing it with commercially available devices is a widespread standard procedure to reduce allogeneic blood transfusion in patients undergoing major orthopedic surgery. The aim of this study was to investigate the impact of such processed blood on the immune system by measuring pro- and anti-inflammatory cytokines. STUDY DESIGN AND METHODS: Salvaged blood from 20 patients undergoing hip arthroplasty was processed with a continuous autotransfusion system. One part of the processed blood was left without further treatment, one part was additionally leukoreduced, one part was irradiated, and one part was separated into its cellular and soluble fraction by centrifugation. Specimens from each part were mixed in vitro with venous blood from the patient in ratios of 3:1, 1:1, and 1:3 and incubated with endotoxin for 24 hours. Tumor necrosis factor (TNF)-α and interleukin (IL)-10 were measured in cell culture supernatants by enzyme-linked immunosorbent assay. RESULTS: All parts of the salvaged blood were without a significant influence on TNF-α release. In contrast, IL-10 was significantly increased, independently of the admixtured salvaged blood being plain, additionally irradiated, or additionally leukoreduced. This IL-10 increase was also found with the cellular fraction of the plain salvaged blood, whereas the soluble fraction had no influence on IL-10 release. CONCLUSION: Intraoperative salvaged blood is not immunologically inert. We observed a significant increase in the anti-inflammatory IL-10 response without affecting the proinflammatory TNF-α release. Neither leukofiltration nor gamma irradiation eliminated this effect that was limited only to the cellular fraction of the salvaged blood, suggesting red blood cells to be responsible for the observed immunomodulation.

Randomized evaluation of the size 2 laryngeal tube and classical laryngeal mask airway in different head and neck positions in children under positive pressure ventilation.

PURPOSE: The aim of this study was to evaluate the applicability of the laryngeal tube (LT) size 2 and the classical laryngeal mask airway (LMA) size 2 in different head-neck positions under positive pressure ventilation in children by measuring leak pressures, peak pressures and the achievable tidal volumes under positive pressure ventilation. METHODS: Forty children were randomized to receive airway management by either the LT or LMA as the primary device. Leak pressures, peak pressures and tidal volumes under positive pressure ventilation were measured in the neutral, anteflection, retroversion, left-rotation and right-rotation head-neck positions. RESULTS: In all head-neck positions, the leak pressures were significantly higher for the LT than for the LMA (neutral 25.9 ± 7.0 vs. 19.1 ± 5.7 cmH2O; anteflection 29.7 ± 7.1 vs. 24.2 ± 8.9 cmH2O; retroversion 24.1 ± 7.6 vs. 17.2 ± 6.9 cmH2O). In both devices, the peak ventilation pressures were higher in the anteflection position (LT 27.1 ± 6.3 cmH2O; LMA 17.8 ± 6.7 cmH2O) than in the retroversion position (LT 13.7 ± 3.9 cmH2O; LMA 12.7 ± 3.6 cmH2O). Compared to the respirator settings, lower tidal volumes were achieved in the anteflection position (LT 65 ± 48 vs. 129 ± 38 ml, LMA 100 ± 21 vs. 125 ± 29 ml) as compared to the other positions. CONCLUSION: Based on our results, we suggest that in anaesthetized children, the size 2 LT, compared to the size 2 LMA, may be more suitable for positive pressure ventilation due to favorable leak and peak pressures. Both devices can be safely used in head-neck positions other than neutral. Most disadvantageous with regards to the measured parameters was the anteflection position, especially for the LT.

Corrigendum: Assessment of Inadequate Use of Pediatric Emergency Medical Transport Services: The Pediatric Emergency and Ambulance Critical Evaluation (PEACE) Study.

[This corrects the article DOI: 10.3389/fped.2019.00442.].

Thoracic but not lumbar epidural anaesthesia increases liver blood flow after major abdominal surgery.

BACKGROUND AND OBJECTIVE: Epidural blockade in major abdominal surgery bears the potential to increase gastrointestinal perfusion and thus to improve patient outcome. The aim of this study was to assess the differential influence of thoracic and lumbar epidural anaesthesia and analgesia (EAA) on blood lactate levels and central venous oxygen saturation (ScvO2) as parameters of global oxygen supply/demand ratio, as well as on the plasma disappearance rate of indocyanine green (PDR(ICG)), a noninvasive method to evaluate liver perfusion. METHODS: We enrolled 17 patients receiving thoracic and 17 patients receiving lumbar EAA in addition to general anaesthesia for major abdominal surgery. Lactate, ScvO2 and PDR(ICG) were measured postoperatively on the ICU. Subsequently, epidural application of local anaesthetics was started with a bolus of bupivacaine 0.25% (thoracic 10 ml, lumbar 12 ml) followed by continuous infusion of bupivacaine (thoracic 8 ml h(-1) 0.175%, lumbar 10 ml h(-1) 0.125%) and fentanyl (2 microg ml(-1)). Central venous pressure was maintained by titrated volume replacement. Lactate, ScvO2 and PDR(ICG) were measured again after 2 h. RESULTS: In both the groups, the mean arterial pressure and heart rate as well as lactate levels and ScvO2 did not change significantly. Although there was a slight but not significant decrease of PDR(ICG) in patients with lumbar EAA (from 25.9 +/- 7.68 to 23.2 +/- 5.90; NS), thoracic EAA resulted in a significant increase of PDR(ICG) (from 21.3 +/- 5.13 to 24.0 +/- 6.66; P < 0.05) for the group mean, but with substantial variability in individual patients in the lumbar EAA group. CONCLUSION: Liver perfusion was increased with thoracic but not lumbar EAA after major abdominal surgery in most patients. PDR(ICG) allows assessment of individual changes of liver blood flow due to therapeutic intervention, for example, EAA.

Comparative pharmacodynamic modeling of desflurane, sevoflurane and isoflurane.

BACKGROUND: We compared dose-response curves of the hypnotic effects of desflurane, sevoflurane and isoflurane. In addition, we analyzed the k(e0) values of the different anesthetics. The EEG parameters Bispectral index (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend index (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as measures of the pharmacodynamic effect. METHODS: With IRB approval and informed consent we analyzed the data of three studies including 61 adult patients scheduled for radical prostatectomies. At least 45 min after induction of general anesthesia, end-tidal concentrations of desflurane, sevoflurane or isoflurane were varied between 0.5 and 2 MAC. We transferred the end-tidal concentrations into age-related MAC values. The relationship between MAC effect compartment concentrations and EEG was modeled with a variation of the classical fractional sigmoid E(max) model with two linked sigmoidal curves. All parameters were calculated as a population fit by NONMEM V (GloboMax, Hanover, USA) by minimizing log likelihood. RESULTS: The k(e0) values of the population fit derived from BIS data were 0.54 min(-1) for desflurane, 0.24 min(-1) for sevoflurane and 0.16 min(-1) for isoflurane, from the Narcotrend index 0.43 min(-1) for desflurane, 0.26 min(-1) for sevoflurane and 0.18 min(-1) for isoflurane. The change between the first and the second sigmoidal curve was positioned at nearly the same Narcotrend- and BIS index values between 41 and 44. CONCLUSIONS: The first order rate constant (k(e0) value) determining the equilibration between age-related MAC values and MAC effect site concentration is substantially higher for desflurane than for sevoflurane or isoflurane.

Assessment of Inadequate Use of Pediatric Emergency Medical Transport Services: The Pediatric Emergency and Ambulance Critical Evaluation (PEACE) Study.

Aim: To provide data on the inadequate use of emergency medical transports services (EMTS) in children and underlying contributing factors. Methods: This was a prospective single-center cohort study (01/2017-12/2017) performed at the Saarland University Children's Hospital, Homburg, Germany. Patients ≤20 years of age transported by EMTS for suspected acute illness/trauma were included and proportion of inadequate/adequate EMTS use, underlying contributing factors, and additional costs were analyzed. Results: Three hundred seventy-nine patients (mean age: 9.0 ± 6.3 years; 55.7% male, 44.3% female) were included in this study. The three most common reasons for EMTS use were: central nervous system (30.6%), respiratory system affection (14.0%), and traumas (13.2%). ETMS use was categorized as inadequate depending on physician's experience: senior physician (58.8%), pediatrician (54.9%), resident (52.7%). All three physicians considered 127 (33.5%) cases to be medically indicated for transportation by EMTS, and 177 (46.7%) to be medically not indicated. The following parameters were significantly associated with inadequate EMTS use: non-acute onset of symptoms (OR 2.5), parental perception as non-life-threatening (OR 1.7), and subsequent out-patient treatment (OR 4.0). Conversely, transport by an emergency physician (OR 3.5) and first time parental EMTS call (OR 1.7) were associated with adequate use of EMTS. Moreover, a significant relation existed between maternal, respectively, paternal educational status and inadequate EMTS use (each p = 0.01). Using multiple logistic regression analysis, non-acute onset of symptoms (OR 2.2) was associated with inadequate use of EMTS while first time parental EMTS call (OR 1.8), transport by an emergency physician (OR 3.3), and need for in-patient treatment (OR 4.0) were associated with adequate use of EMTS. Conclusion: A substantial number of pediatric EMTS is medically not indicated. Possibly, specific measures including multifaceted educational efforts may be helpful in reducing unnecessary EMTS use.

The performance of six pulse oximeters in the environment of neuronavigation.

BACKGROUND: Although the use of pulse oximeters may be regarded a standard of care for monitoring anesthesia procedures, these monitors may be susceptible to various kinds of disturbances. Recently, it was suggested that neuronavigation equipment may interfere with pulse oximeter accuracy. In this study, we evaluated the effect of a neurosurgical image guidance system on the performance of six different pulse oximeters. Two simple shielding methods were evaluated. METHODS: Twenty healthy, adult, nonsmoking volunteers were equipped with six different pulse oximeters on both hands. Baseline values for heart rate, arterial oxygen saturation, and signal quality were assessed. After activation of the Brain Lab VectorVision Neuronavigation System, the effects on signal quality and saturation recognition were evaluated. Measurements were repeated using two different shielding techniques, a cotton blanket and aluminum sheets. RESULTS: Activation of the image guidance system resulted in a significant disturbance of signal quality and saturation detection, which was partially reversible by both shielding techniques. Significant differences were noted among the six brands of pulse oximeters for signal quality (P < 0.001) and saturation recognition (P < 0.001), and for the response to shielding methods (P < 0.001). Coverage of the probes with aluminum foil resulted an in undisturbed saturation recognition in all subjects with almost all monitors. CONCLUSIONS: Infrared pulse waves from neurosurgical navigation equipment may interfere with pulse oximeter measurements. Shielding the probe with aluminum foil sufficiently eliminated the infrared interference.

Comparative pharmacodynamic modeling using bispectral and narcotrend-index with and without a pharmacodynamic plateau during sevoflurane anesthesia.

BACKGROUND: We compared two pharmacodynamic models, one with and one without a plateau effect. Bispectral indices (BIS, Aspect Medical Systems, Natick, MA, version XP) and Narcotrend (NCT, MonitorTechnik, Bad Bramstedt, Germany, version 4.0) were used as an electroencephalographic measure of sevoflurane drug effect. In addition, we tried to analyze the origin of the plateau. METHODS: We investigated 26 adult patients scheduled for radical prostatectomy. At least 45 min after induction of general anesthesia, end-tidal sevoflurane concentrations were varied between 1 vol% and 4 vol%. To evaluate the relationship between concentrations and electroencephalographic indices, two different pharmacodynamic models were applied: a conventional model based on a single sigmoidal curve, and a novel model based on two sigmoidal curves for BIS and NCT values with and without burst suppression. The parameters of the models were estimated by NONMEM V (GloboMax, Hanover) by minimizing log likelihood. Statistical significance between the two models was calculated by the likelihood ratio test. RESULTS: The end-tidal sevoflurane concentration ranged from 1.04 +/- 0.17 vol% to 4.43 +/- 0.43 vol%. The difference between the log likelihood values of the new pharmacokinetic/pharmacodynamic model with two connected sigmoidal curves and the classical E(max) model with one sigmoidal curve is 396 (P < 0.001) for the BIS monitor and 1121 (P < 0.001) for the NCT. The plateau is positioned at the change between the maximum delta power and the increase of burst suppression ratio. CONCLUSION: A pharmacokinetic/pharmacodynamic model consisting of two sigmoid curves with an intervening plateau describes the effect of sevoflurane on BIS and NCT indices better than a model with a single sigmoid curve.

The efficacy of the non-opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy.

In this prospective, double-blind, randomized, placebo-controlled study we compared the efficacy of three IV non-opioid analgesics for postoperative pain relief after lumbar microdiscectomy. Eighty healthy patients were randomly divided into 4 treatment groups (n = 20 each) to receive either parecoxib 40 mg, paracetamol 1 g, metamizol 1 g, or placebo IV 45 min before the end of surgery. In the postanesthesia care unit (PACU) patients were treated using patient-controlled analgesia (PCA) with piritramide. In the metamizol group the pain score at arrival in the PACU was significantly lower compared with the paracetamol, parecoxib, and placebo groups. In addition, in the metamizol group significantly fewer patients required additional PCA compared with the other groups studied. However, in those patients who required additional pain therapy in the four treatment groups, there was no significant difference in time to first request for piritramide and cumulative consumption of piritramide as assessed by the PCA data in the PACU. The incidence of adverse side effects was infrequent in all groups. These results suggest that in patients undergoing lumbar microdiscectomy, metamizol is superior to parecoxib, paracetamol, and placebo for immediate postoperative pain relief with minimal side effects.

Monocyte deactivation in severe human sepsis or following cardiopulmonary bypass.

We investigated the specificity for gram-negative stimuli as well as the contribution of signal transduction pathways for leukocyte hyporesponsiveness in sepsis or following cardiopulmonary bypass (CPB). Whole blood of nine patients undergoing CPB and 25 patients with severe sepsis was stimulated ex vivo with LPS (E. coli O111:B4) or with Staphylococcus aureus Cowan strain I (SAC-I) lysate in the absence or presence of inhibitors of protein kinase C (PKC), protein-tyrosine kinase (PTK), or protein-tyrosine phosphatase (PTP). Both toxins stimulated a TNF-alpha response through PTK signaling. Although suppression of the cytokine response was similar for LPS and SAC-I after CPB, it was significantly more pronounced for SAC-I in sepsis. Inhibition of PTP failed to increase TNF-alpha upon LPS, whereas a moderate increase was observed with SAC-I. Impaired TNF-alpha responses occur in sepsis and after CPB. Although this has primarily been reported for gram-negative stimuli, our data suggest that this is even more pronounced for gram-positive stimuli in severe sepsis. Although PTK was the predominant signaling pathway, inhibition of PTP only partially restored the TNF-alpha response to SAC-I. Our results suggest that cellular mechanisms underlying monocyte deactivation are different in sepsis or following CPB and are discriminate for gram-positive and gram-negative toxins.

Parker Flex-It intubation stylet versus a 90-degree curved stylet during intubation with the McGrath videolaryngoscope performed by novices: a manikin study with 5 airway scenarios.

STUDY OBJECTIVE: To compare the Parker Flex-It intubation stylet with a 90-degree curved stylet using the McGrath videolaryngoscope in 5 airway scenarios (from easy to difficult) in a manikin. DESIGN: Prospective, randomized study. SETTING: Academic hospital. SUBJECTS: 20 staff anesthesiologists with no previous experience in videolaryngoscopy. MEASUREMENTS: Subjects performed a total of 200 intubations with the McGrath Series 5 videolaryngoscope and completed a questionnaire afterwards. RESULTS: Overall success rate was significantly higher with the Parker Flex-It intubation stylet (96 successful intubations with the Parker Flex-It vs 79 intubations in the 90° curved stylet group; P < 0.05). Intubation time was not significantly different. Subjects rated the Parker Flex-It intubation stylet as the better device for intubation with the McGrath videolaryngoscope in routine or emergency situations. CONCLUSION: Intubation of the manikin with the McGrath videolaryngoscope had more success with the Parker Flex-It intubation stylet than a 90° curved stylet.

Delayed-type heparin allergy: diagnostic procedures and treatment alternatives-a case series including 15 patients.

Delayed-type hypersensitivity reactions (DTHRs) after subcutaneous application of unfractionated heparins or low-molecular-weight heparins are not uncommon. Standard allergological testing usually includes intracutaneous skin tests and patch testing of different heparins, heparinoids, and thrombin inhibitors followed by subcutaneous and/or intravenous challenge with skin test-negative drugs. We present data from a single-center case series of 15 patients with DTHR after low-molecular-weight heparin administration. Intracutaneous testing that can be considered as gold standard identified the suspicious elicitor in 11 (73.4%) of 15 of the patients. Patch testing was positive in 5 (33.4%) of 15 of the patients and was only positive in patients who were also reacting in the intradermal testing. Intravenous challenge with heparin sodium was performed in 10 of 15 patients and was well tolerated in all cases, despite prior positive intracutaneous tests with the same substance. Intracutaneous documentation of DTHR was not an adequate predictor of intravenous challenge.

Sedation and analgesia for brief diagnostic and therapeutic procedures in children.

The number of diagnostic and therapeutic procedures done outside of the operating room and the intensive care unit has increased substantially in recent years. In parallel, the management of acute pain and anxiety in children undergoing therapeutic and diagnostic procedures has developed considerably in the past two decades. The primary goal of procedural sedation and analgesia is the safe and efficacious control of emotional distress and pain. The availability of non-invasive monitoring, short-acting opioids and sedatives has broadened the possibilities of sedation and analgesia in children in diverse settings. While most of these procedures themselves pose little risk to the child, the administration of sedation or analgesia may add substantial risk to the patient. This article reviews the current status of sedation and analgesia for invasive and non-invasive procedures in children providing an evidence-based approach to several topics of importance, including patient assessment, personnel requirements, equipment, monitoring, and drugs.

Hemodynamic response to exercise as measured by the solar IKG impedance cardiography module and correlation with metabolic variables.

OBJECTIVE: Impedance Cardiography (ICG) has been shown to be a feasible and accurate method for non-invasive measurement of cardiac index (CI). Aim of this investigation was the correlation of hemodynamic variables under exercise as measured by a specific ICG-monitor (Solar IKG-Modul, Version 3.0, GE-Healthcare, Freiburg, Germany) with metabolic variables. METHODS: Ten healthy volunteers were included in the investigation doing ergometer exercise (5 min equilibration followed by 5 min each at 50, 75, 100 and 125 W). Hemodynamic parameters were obtained by ICG. Metabolic variables were assessed by indirect calorimetry with the Deltatrac II Metabolic monitor using a helmet system for spontaneous respiration. RESULTS: CI increased throughout exercise (baseline: 3.0 +/- 0.4 l/min/m(2); 125 W: 4.8 +/- 0.5 l/min/m(2)). Heart rate (baseline: 87.2 +/- 13.4 bpm; 125 W: 152.7 +/- 22.4 bpm) and contractility (velocity index) (baseline: 48.9 +/- 9.3/1000 s; 125 W: 70.5 +/- 10.0/1000 s) showed a continuous rise while the stroke index decreased after an initial rise (baseline: 35.0 +/- 4.6 ml/m(2); 50 W: 37.6 +/- 4.9 ml/m(2); 75 W: 41.2 +/- 5.9 ml/m(2); 125 W: 32.3 +/- 6.1 ml/m(2)). VO(2) (baseline: 335.2 +/- 84.1 ml/min; 125 W: 1298.9 +/- 282.3 ml/min) and VCO(2)(baseline: 255.4 +/- 74.5 ml/min; 125 W: 1342.5 +/- 282.5 ml/min) increased throughout exercise. There was a good correlation in the individual fits between hemodynamic and metabolic variables. CONCLUSION: CI in healthy volunteers, as measured by the Solar IKG-Modul, correlates well with O(2)-consumption and CO(2)-production in individual subjects, thus indicating the metabolic needs under exercise conditions in healthy individuals.

Narcotrend index versus bispectral index as electroencephalogram measures of anesthetic drug effect during propofol anesthesia.

UNLABELLED: The Narcotrend monitor (MonitorTechnik, Bad Bramstedt, Germany) performs an automatic analysis of the electroencephalogram (EEG) during anesthesia based on a visual assessment of the raw EEG. Its newest software version 4.0 includes a dimensionless index that, similar to the bispectral index (BIS), ranges from 100 (awake) to 0. We compared the performance of Narcotrend index and BIS as EEG measures of anesthetic drug effect during propofol anesthesia. Eighteen adult patients scheduled for radical prostatectomy were investigated. An epidural catheter was placed in the lumbar space and electrodes for BIS (version XP; Aspect Medical Systems, Natick, MA) and Narcotrend were positioned as recommended by the manufacturers. Narcotrend index, BIS values, and propofol plasma and effect site concentrations as parallelly simulated by Rugloop software (Department of Anesthesia, Ghent University, Belgium) were automatically recorded in intervals of 5 s. Induction of anesthesia consisted of a fentanyl bolus and a propofol infusion. After endotracheal intubation, patients received 15 mL bupivacaine 0.5% epidurally, and 45 min later propofol dosages were subsequently increased and decreased twice. Simulated propofol effect site concentrations ranged from 2.0 +/- 0.4 microg/mL (smallest) to 6.3 +/- 1.3 microg/mL (largest) during these subsequent increases and decreases of propofol. In terms of prediction probability (P(K)) the performance of the Narcotrend index (P(K) = 0.88 +/- 0.03) to predict propofol effect site concentrations was comparable to the BIS (P(K) = 0.85 +/- 0.04). Using the respective EEG index as a measure of drug effect the mean k(e0) was calculated as 0.20 +/- 0.05 min(-1) for Narcotrend index and 0.16 +/- 0.07 min(-1) for BIS. In the observed propofol concentration range Narcotrend index detected differences in EEG dynamics as well as BIS. IMPLICATIONS: This study in 18 adult patients undergoing radical prostatectomy describes the relationship between Narcotrend index and bispectral index versus predicted propofol effect compartment concentrations. In terms of prediction probability, the performance of the Narcotrend index and the bispectral index to predict propofol effect site concentrations was comparable.