Rebounds of sevoflurane concentration during simulated trigger-free pediatric and adult anesthesia.

BACKGROUND: In trigger-free anesthesia a volatile anesthetic concentration of 5 parts per million (ppm) should not be exceeded. According to European Malignant Hyperthermia Group (EMHG) guideline, this may be achieved by removing the vapor, changing the anesthetic breathing circuit and renewing the soda lime canister followed by flushing with O2 or air for a workstation specific time. Reduction of the fresh gas flow (FGF) or stand-by modes are known to cause rebound effects. In this study, simulated trigger-free pediatric and adult ventilation was carried out on test lungs including ventilation maneuvers commonly used in clinical practice. The goal of this study was to evaluate whether rebounds of sevoflurane develop during trigger-free anesthesia. METHODS: A Dräger® Primus® was contaminated with decreasing concentrations of sevoflurane for 120 min. Then, the machine was prepared for trigger-free anesthesia according to EMHG guideline by changing recommended parts and flushing the breathing circuits using 10 or 18 l⋅min- 1 FGF. The machine was neither switched off after preparation nor was FGF reduced. Simulated trigger-free ventilation was performed with volume-controlled ventilation (VCV) and pressure-controlled ventilation (PCV) including various ventilation maneuvers like pressure support ventilation (PSV), apnea, decreased lung compliance (DLC), recruitment maneuvers, prolonged expiration and manual ventilation (MV). A high-resolution ion mobility spectrometer with gas chromatographic pre-separation was used to measure sevoflurane in the ventilation gas mixture in a 20 s interval. RESULTS: Immediately after start of simulated anesthesia, there was an initial peak of 11-18 ppm sevoflurane in all experiments. The concentration dropped below 5 ppm after 2-3 min during adult and 4-18 min during pediatric ventilation. Other rebounds of sevoflurane > 5 ppm occurred after apnea, DLC and PSV. MV resulted in a decrease of sevoflurane < 5 ppm within 1 min. CONCLUSION: This study shows that after guideline-compliant preparation for trigger-free ventilation anesthetic machines may develop rebounds of sevoflurane > 5 ppm during typical maneuvers used in clinical practice. The changes in rate and direction of internal gas flow during different ventilation modes and maneuvers are possible explanations. Therefore, manufacturers should provide machine-specific washout protocols or emphasize the use of active charcoal filters (ACF) for trigger-free anesthesia.

Preparation of Dräger Atlan A350 and General Electric Healthcare Carestation 650 anesthesia workstations for malignant hyperthermia susceptible patients.

BACKGROUND: Patients at risk of malignant hyperthermia need trigger-free anesthesia. Therefore, anesthesia machines prepared for safe use in predisposed patients should be free of volatile anesthetics. The washout time depends on the composition of rubber and plastic in the anesthesia machine. Therefore, new anesthesia machines should be evaluated regarding the safe preparation for trigger-free anesthesia. This study investigates wash out procedures of volatile anesthetics for two new anesthetic workstations: Dräger Atlan A350 and General Electric Healthcare (GE) Carestation 650 and compare it with preparation using activated charcoal filters (ACF). METHODS: A Dräger Atlan and a Carestation 650 were contaminated with 4% sevoflurane for 90 min. The machines were decontaminated with method (M1): using ACF, method 2 (M2): a wash out method that included exchange of internal parts, breathing circuits and soda lime canister followed by ventilating a test lung using a preliminary protocol provided by Dräger or method 3 (M3): a universal wash out instruction of GE, method 4 (M4): M3 plus exchange of breathing system and bellows. Decontamination was followed by a simulated trigger-free ventilation. All experiments were repeated with 8% desflurane contaminated machines. Volatile anesthetics were detected with a closed gas loop high-resolution ion mobility spectrometer with gas chromatographic pre-separation attached to the bacterial filter of the breathing circuits. Primary outcome was time until < 5 ppm of volatile anesthetics and total preparation time. RESULTS: Time to < 5 ppm for the Atlan was 17 min (desflurane) and 50 min (sevoflurane), wash out continued for a total of 60 min according to protocol resulting in a total preparation time of 96-122 min. The Carestation needed 66 min (desflurane) and 24 min (sevoflurane) which could be abbreviated to 24 min (desflurane) if breathing system and bellows were changed. Total preparation time was 30-73 min. When using active charcoal filters time to < 5 ppm was 0 min for both machines, and total preparation time < 5 min. CONCLUSION: Both wash out protocols resulted in a significant reduction of trace gas concentrations. However, due to the complexity of the protocols and prolonged total preparation time, feasibility in clinical practice remains questionable. Especially when time is limited preparation of the anesthetic machines using ACF remain superior.

Correlation of exhaled propofol with Narcotrend index and calculated propofol plasma levels in children undergoing surgery under total intravenous anesthesia - an observational study.

BACKGROUND: Exhaled propofol concentrations correlate with propofol concentrations in adult human blood and the brain tissue of rats, as well as with electroencephalography (EEG) based indices of anesthetic depth. The pharmacokinetics of propofol are however different in children compared to adults. The value of exhaled propofol measurements in pediatric anesthesia has not yet been investigated. Breathing system filters and breathing circuits can also interfere with the measurements. In this study, we investigated correlations between exhaled propofol (exP) concentrations and the Narkotrend Index (NI) as well as calculated propofol plasma concentrations. METHODS: A multi-capillary-column (MCC) combined with ion mobility spectrometry (IMS) was used to determine exP. Optimal positioning of breathing system filters (near-patient or patient-distant) and sample line (proximal or distal to filter) were investigated. Measurements were taken during induction (I), maintenance (M) and emergence (E) of children under total intravenous anesthesia (TIVA). Correlations between ExP concentrations and NI and predicted plasma propofol concentrations (using pediatric pharmacokinetic models Kataria and Paedfusor) were assessed using Pearson correlation and regression analysis. RESULTS: Near-patient positioning of breathing system filters led to continuously rising exP values when exP was measured proximal to the filters, and lower concentrations when exP was measured distal to the filters. The breathing system filters were therefore subsequently attached between the breathing system tubes and the inspiratory and expiratory limbs of the anesthetic machine. ExP concentrations significantly correlated with NI and propofol concentrations predicted by pharmacokinetic models during induction and maintenance of anesthesia. During emergence, exP significantly correlated with predicted propofol concentrations, but not with NI. CONCLUSION: In this study, we demonstrated that exP correlates with calculated propofol concentrations and NI during induction and maintenance in pediatric patients. However, the correlations are highly variable and there are substantial obstacles: Without patient proximal placement of filters, the breathing circuit tubing must be changed after each patient, and furthermore, during ventilation, a considerable additional loss of heat and moisture can occur. Adhesion of propofol to plastic parts (endotracheal tube, breathing circle) may especially be problematic during emergence. TRIAL REGISTRATION: The study was registered in the German registry of clinical studies (DRKS-ID:  DRKS00015795 ).

Relevance of pathogenicity prediction tools in human RYR1 variants of unknown significance.

Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle metabolism characterized by generalized muscle rigidity, increased body temperature, rhabdomyolysis, hyperkalemia and severe metabolic acidosis. The underlying mechanism of MH involves excessive Ca2+ release from myotubes via the ryanodine receptor type 1 (RYR1) and the voltage-dependent L-type calcium channel (CACNA1S). As more than 300 variants of unknown significance have been detected to date, we examined whether freely available pathogenicity prediction tools are able to detect relevant MH causing variants. In this diagnostic accuracy study, blood samples from 235 individuals with a history of a clinical malignant hyperthermia or their close relatives were genetically screened for RYR1 variants of all 106 RYR1 exons and additionally for known variants of CACNA1S. In vitro contracture tests were conducted on muscle biopsies obtained from all individuals, independently of whether a pathogenic variant, a variant of unknown significance or no variant was detected. Comparisons were made to three established bioinformatic pathogenicity detection tools to identify the clinical impact of the variants of unknown significance. All detected genetic variants were tested for pathogenicity by three in silico approaches and compared to the in vitro contracture test. Sensitivity and specificity of exon screening of all individuals listed in our MH database was analyzed. Exon screening identified 97 (41%) of the 235 individuals as carriers of pathogenic variants. Variants of unknown significance were detected in 21 individuals. Variants of unknown significance were subdivided into 19 malignant-hyperthermia-susceptible individuals and 2 non-malignant-hyperthermia-susceptible individuals. All pathogenic variants as well as the malignant-hyperthermia-suspectible variants were correctly identified by the bioinformatic prediction tools. Sensitivity of in silico approaches ranged between 0.71 and 0.98 (Polyphen 0.94 [CI 95% 0.75; 0.99]; Sift 0.98 [CI 95% 0.81; 0.99]; MutationTaster 0.92 [CI 95% 0.75; 0.99]). Specificity differed depending on the used tool (Polphen 0.98 [CI 95% 0.32; 0.99]; Sift 0.98 [CI 95% 0.32; 0.99]; MutationTaster 0.00 [CI 95% 0.00; 0.60]). All pathogenic variants and variants of unknown significance were scored as probably damaging in individuals, demonstrating a high sensitivity. Specificity was very low in one of the three tested programs. However, due to potential genotype-phenotype discordance, bioinformatic prediction tools are currently of limited value in diagnosing pathogenicity of MH-susceptible variants.

Consensus guidelines on perioperative management of malignant hyperthermia suspected or susceptible patients from the European Malignant Hyperthermia Group.

Malignant hyperthermia is a potentially fatal condition, in which genetically predisposed individuals develop a hypermetabolic reaction to potent inhalation anaesthetics or succinylcholine. Because of the rarity of malignant hyperthermia and ethical limitations, there is no evidence from interventional trials to inform the optimal perioperative management of patients known or suspected with malignant hyperthermia who present for surgery. Furthermore, as the concentrations of residual volatile anaesthetics that might trigger a malignant hyperthermia crisis are unknown and manufacturers' instructions differ considerably, there are uncertainties about how individual anaesthetic machines or workstations need to be prepared to avoid inadvertent exposure of susceptible patients to trigger anaesthetic drugs. The present guidelines are intended to bundle the available knowledge about perioperative management of malignant hyperthermia-susceptible patients and the preparation of anaesthesia workstations. The latter aspect includes guidance on the use of activated charcoal filters. The guidelines were developed by members of the European Malignant Hyperthermia Group, and they are based on evaluation of the available literature and a formal consensus process. The most crucial recommendation is that malignant hyperthermia-susceptible patients should receive anaesthesia that is free of triggering agents. Providing that this can be achieved, other key recommendations include avoidance of prophylactic administration of dantrolene; that preoperative management, intraoperative monitoring, and care in the PACU are unaltered by malignant hyperthermia susceptibility; and that malignant hyperthermia patients may be anaesthetised in an outpatient setting.

Prevention of postoperative bleeding after complex pediatric cardiac surgery by early administration of fibrinogen, prothrombin complex and platelets: a prospective observational study.

BACKGROUND: Postoperative bleeding is a major problem in children undergoing complex pediatric cardiac surgery. The primary aim of this prospective observational study was to evaluate the effect of an institutional approach consisting of early preventive fibrinogen, prothrombin complex and platelets administration on coagulation parameters and postoperative bleeding in children. The secondary aim was to study the rate of re-intervention and postoperative transfusion, the occurrence of thrombosis, length of mechanical ventilation, ICU stay and mortality. METHODS: In fifty children (age 0-6 years) with one or more predefined risk factors for bleeding after cardiopulmonary bypass (CPB), thrombelastography (TEG) and standard coagulation parameters were measured at baseline (T1), after CPB and reversal of heparin (T2), at sternal closure (T3) and after 12 h in the ICU (T4). Clinical bleeding was evaluated by the surgeon at T2 and T3 using a numeric rating scale (NRS, 0-10). RESULTS: After CPB and early administration of fibrinogen, prothrombin complex and platelets, the clinical bleeding evaluation score decreased from a mean value of 6.2 ± 1.9 (NRS) at T2 to a mean value of 2.1 ± 0.8 at T3 (NRS; P <  0.001). Reaction time (R), kinetic time (K), maximum amplitude (MA) and maximum amplitude of fibrinogen (MA-fib) improved significantly (P <  0.001 for all), and MA-fib correlated significantly with the clinical bleeding evaluation (r = 0.70, P <  0.001). The administered total amount of fibrinogen (mg kg- 1) correlated significantly with weight (r = - 0.42, P = 0.002), priming volume as percentage of estimated blood volume (r = 0.30, P = 0.034), minimum CPB temperature (r = - 0.30, P = 0.033) and the change in clinical bleeding evaluation from T2 to T3 (r = 0.71, P <  0.001). The incidence of postoperative bleeding (> 10% of estimated blood volume) was 8%. No child required a surgical re-intervention, and no cases of thrombosis were observed. Hospital mortality was 0%. CONCLUSION: In this observational study of children with an increased risk of bleeding after CPB, an early preventive therapy with fibrinogen, prothrombin complex and platelets guided by clinical bleeding evaluation and TEG reduced bleeding and improved TEG and standard coagulation parameters significantly, with no occurrence of thrombosis or need for re-operation. TRIAL REGISTRATION: German Clinical Trials Register DRKS00018109 (retrospectively registered 27th August 2019).

Ultrasound assessment of gastric emptying time after intake of clear fluids in children scheduled for general anesthesia-A prospective observational study.

BACKGROUND: While many clinics have changed their local regimen toward a more liberal policy regarding clear fluid fasting for general anesthesia, there is a lack of studies evaluating gastric emptying time in a clinical setting. AIMS: Based on this and before implementation of a more liberal preoperative clear fluid fasting policy for children, we studied gastric emptying time of clear fluids in children and hypothesized that the mean gastric emptying time would be 1 hour. METHODS: Between March and December 2019, children scheduled for general anesthesia at our University Children's Hospital were enrolled in this prospective observational study. After overnight fasting, gastric emptying was examined by sonographic measurements of the gastric antral area before and 5, 15, 30, 45, and 60 minutes after intake of water or fruit juice. RESULTS: Twenty-six children were enrolled in this study, and 24 aged 11 (range 4-17) years were included for statistical analysis. The median ingested fluid volume was 4.7 (range 1.8-11.8) mL kg-1 . The gastric antral area of the children initially increased and subsequently decreased after intake of clear fluids and correlated significantly with fasting time (r = -0.55, P < .0001). After 1 hour, the gastric antral area had returned to the baseline level in 20 children but not in four children with a fluid intake >5 mL kg-1 . There was no difference in the gastric antral area between water and fruit juice. Using a linear regression model, the calculated mean gastric emptying time of clear fluids was 52 minutes. CONCLUSION: This study showed that the gastric emptying time of children after intake up to 5 mL kg-1 clear fluids was <1 hour in a clinical setting. These results support the more liberal fasting regimen favoring a 1-hour fasting time and suggest 5 mL kg-1 as an upper limit for clear fluids (eg, water, sugared water or tea or diluted fruit juice) from 2 hours to 1 hour before induction of anesthesia in children.

Stability of 0.5% Glucose-Containing Balanced Electrolyte Solutions for Patients on Ketogenic Diets: A Laboratory Study.

PURPOSE: Ketogenic diets (KDs) are used to treat epilepsies resistant to pharmacotherapy or some inborn errors of metabolism. For prolonged anesthesia, use of balanced electrolyte solutions (BESs) supplemented with 0.5% glucose has been advocated to maintain ketosis while preventing hypoglycemia. Unfortunately, there is no BES containing 0.5% glucose available from pharmacies. In a laboratory study, we investigated the physical and chemical stability of different BES mixtures containing 0.5% glucose. METHODS: In total, six approaches were chosen to create a BES with 0.5% glucose: three different glucose-free BESs were supplemented with glucose. Additionally, commercially available BES containing 1% glucose was diluted with three different glucose-free BESs to obtain a solution containing 0.5% glucose. Turbidity, pH, electrical conductivity, and macroscopic appearance of these solutions were measured immediately, at 24 hours, and after 7 days, and were compared with the original BES. RESULTS: Turbidity, pH, and electrical conductivity, as well as macroscopic appearance did not exceed the changes of the controls. CONCLUSIONS: No signs of incompatibility reactions could be observed in a 1-week time period. Our study supports the stability of the examined BES containing 0.5% glucose for prolonged anesthesia in patients on KD. Clinical studies are needed to evaluate if BES containing 0.5% glucose is superior in patients on KDs.

Effect of etomidate on systemic and regional cerebral perfusion in neonates and infants with congenital heart disease: A prospective observational study.

BACKGROUND: Neonates and infants with congenital heart disease undergoing general anesthesia have an increased risk for critical cardiovascular events. Etomidate produces very minimal changes in hemodynamic parameters in older children with congenital heart disease. There is a lack of studies evaluating the effect of etomidate on systemic and regional cerebral perfusion in neonates and infants with congenital heart disease. AIM: The aim of this prospective observational study was to evaluate the effect of etomidate on systemic and regional cerebral perfusion in neonates and infants with congenital heart disease. METHODS: In fifty infants aged 0-11 months (24% neonates n = 12) with congenital heart disease, mean arterial blood pressure, cardiac index using electrical cardiometry, and regional cerebral oxygen saturation using near-infrared spectroscopy were measured at baseline and 1, 3, 5, and 10 minutes after induction by 0.4 mg kg-1 etomidate. Hypotension was defined as a mean arterial blood pressure under 35 mm Hg and cerebral desaturation as a regional cerebral oxygen saturation of less than 80% of baseline. RESULTS: Mean arterial blood pressure, cardiac index, and regional cerebral oxygen saturation remained stable above the predefined limits. Mean arterial blood pressure decreased slightly within a physiological range after 3 minutes (P = .005, 95% CI:-5.9 to -1.0). No significant change in cardiac index could be observed. CONCLUSION: Etomidate 0.4mg kg-1 does not impair systemic or regional cerebral perfusion in neonates or infants with congenital heart disease.

Preparation of anaesthesia workstation for trigger-free anaesthesia: An observational laboratory study.

BACKGROUND: Trigger-free anaesthesia is required for patients who are susceptible to malignant hyperthermia. Therefore, all trace of volatile anaesthetics should be removed from anaesthetic machines before induction of anaesthesia. Because the washout procedure is time consuming, activated charcoal filters have been introduced, but never tested under minimal flow conditions. OBJECTIVE: To investigate performance of activated charcoal filters during long duration (24 h) simulated ventilation. DESIGN: A bench study. SETTING: A Primus anaesthesia machine (Dräger) was contaminated with either 4% sevoflurane or 8% desflurane by ventilating a test lung for 90 min. The machine was briefly flushed according to manufacturer instructions, activated charcoal filters were inserted and a test lung was ventilated in a 24 h test. Trace gas concentrations were measured using a closed gas loop high-resolution ion mobility spectrometer with gas chromatographic preseparation. During the experiment reduced fresh gas flows were tested. At the end of each experiment the activated charcoal filters were removed and the machine was set to standby for 10 min to test for residual contamination within the circuit. The activated charcoal filters were reconnected into the circuit to test their ability to continue removing volatile anaesthetics (functional test) from the gas. Control experiments were conducted without activated charcoal filters. MAIN OUTCOME MEASURES: Absolute concentrations of desflurane and sevoflurane. RESULTS: The concentration of volatile anaesthetics dropped to less than 5 ppm (parts per million) following insertion of activated charcoal filters. In the desflurane experiments at least 1 l min FGF was needed to keep the concentration below an acceptable level (<5 ppm): 0.5 l min fresh gas flow was required in sevoflurane experiments. While activated charcoal filters in the sevoflurane tests passed the functional test after 24 h, activated charcoal filters in the desflurane tests failed. CONCLUSION: Activated charcoal filters meet the requirements for trigger-free low flow (1 l min) ventilation over 24 h. Minimal flow (0.5 l min) ventilation may be possible for sevoflurane contaminated machines.

Low anaesthetic waste gas concentrations in postanaesthesia care unit: A prospective observational study.

BACKGROUND: Volatile anaesthetics are a potential hazard during occupational exposure, pregnancy or in individuals with existing disposition to malignant hyperthermia. Anaesthetic waste gas concentration in postanaesthesia care units (PACU) has rarely been investigated. OBJECTIVE(S): The current study aims to assess concentrations of volatile anaesthetics in relation to room size, number of patients and ventilator settings in different PACUs. DESIGN: A prospective observational study. SETTING: Two different PACUs of the Hannover Medical School (Hannover, Germany) were evaluated in this study. The rooms differed in dimensions, patient numbers and room ventilation settings. PATIENTS: During the observation period, sevoflurane anaesthesia was performed in 65 of 140 patients monitored in postanaesthesia unit one and in 42 of 70 patients monitored in postanaesthesia unit two. MAIN OUTCOME MEASURES: Absolute trace gas room concentrations of sevoflurane measured with a compact, closed gas loop high-resolution ion mobility spectrometer. RESULTS: Traces of sevoflurane could be detected in 805 out of 970 samples. Maximum concentrations were 0.96 ±â€Š0.20 ppm in postanaesthesia unit one, 0.82 ±â€Š0.07 ppm in postanaesthesia unit two. Median concentration was 0.12 (0.34) ppm in postanaesthesia unit one and 0.11 (0.28) ppm in postanaesthesia unit two. CONCLUSION: Low trace amounts of sevoflurane were detected in both PACUs equipped with controlled air exchange systems. Occupational exposure limits were not exceeded.

Compatibility of common IV drugs with 6% hydroxyethyl starch 130/0.42 and 4% gelatin.

BACKGROUND: Acetate-containing colloid infusion solutions are recommended to recover normovolemia during pediatric anesthesia. Until now, no studies investigating the compatibility with common anesthetic drugs were available. AIMS: This in vitro study was conducted to reveal possible incompatibilities between common anesthetic drugs and the acetate-containing colloid infusion solutions 6% hydroxyethyl starch and 4% gelatin with normal saline as control. METHODS: The colloid infusion solutions were mixed 1:1 with 29 common intravenous drugs in concentrations used in daily clinical practice. Macroscopically visible changes as well as electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured immediately after mixing and subsequently 30 and 60 minutes later. All experiments were conducted in triplicate. RESULTS: Fifty-nine of the 87 colloid infusion-drug mixtures showed no significant changes in pH, electrical conductivity, turbidimetrically detectable light diffusion, or macroscopic appearance after mixing with hydroxyethyl starch, gelatin, and NaCl 0.9%. Fifteen mixtures showed equivocal reactions, and 13 mixtures showed incompatibility reactions. CONCLUSION: Most of the tested drugs did not show observable incompatibility reactions. However, some common drugs are highly incompatible with colloid infusion solutions: gelatin (cefazolin, diazepam, midazolam, phenytoin, vancomycin), hydroxyethyl starch (diazepam, midazolam, phenytoin, thiopental), and NaCl 0.9% (diazepam, ketamine (S), phenytoin, thiopental). These combinations should be avoided in clinical practice in case there are fewer intravenous lines available than needed.

Impact of temperature on the Narcotrend Index during hypothermic cardiopulmonary bypass in children with sevoflurane anesthesia.

BACKGROUND: During cardiopulmonary bypass (CPB) in children, anesthesia maintained by sevoflurane administered via the oxygenator is increasingly common. Anesthetic uptake and requirement may be influenced by the non-physiological conditions during hypothermic CPB. Narcotrend-processed EEG monitoring may, therefore, be useful to guide the administration of sevoflurane during this phase. OBJECTIVE: The objective of this prospective, clinical, observational study was to assess the correlation between body temperature, Narcotrend Index (NI) and administered sevoflurane in children during CPB. METHODS: Forty-four children aged 0 to 10 years undergoing hypothermic cardiac surgery were studied. On bypass, anesthesia was maintained with sevoflurane administered via the oxygenator of the heart-lung machine. Nasopharyngeal temperature, NI and minimum alveolar concentration (MAC) of sevoflurane were recorded in intervals of 10 minutes. Expiratory gas was sampled from the oxygenator's sole expiratory port via a separate connecting line and the MAC was measured by the agent analyzer of the anesthesia machine. RESULTS: Raw (r = 0.74) and corrected (r = 0.73) r-values show that narcosis depth (as indicated by NI) can primarily be explained by the interaction of MAC and temperature. The analysis of variance (without the interaction term) confirms the significant and independent association of both factors, MAC (p<0.004, 95%CI: 0.19 to 0.46) and temperature (p<0.0001, 95%CI: 0.68 to 0.78), with the NI. During hypothermia, sevoflurane had been reduced significantly (r = 0.41, p<0.0001, 95%CI: 0.33 to 0.48). CONCLUSION: Perfusionists and anesthetists should be aware of the results of processed electroencephalograph (EEG) monitoring during CPB. Sevoflurane requirements differ inter-individually; they may decrease during cooling and increase during rewarming. Therefore, it seems reasonable to include the results of processed EEG monitoring when administering sevoflurane during CPB in children, but further studies are necessary to confirm this thesis.

Effect of age on Narcotrend Index monitoring during sevoflurane anesthesia in children below 2 years of age.

BACKGROUND: In older children, different electroencephalogram-based algorithms for measuring depth of anesthesia displayed a similar performance as in adults, but in infants they have not displayed the same reliability so far. According to the individual developmental state, the Narcotrend distinguishes "differentiated" electroencephalograms, which can be classified using the full Narcotrend Index scale, from "undifferentiated" electroencephalograms, which are classified using a scale with fewer stages. OBJECTIVE: The objective of this prospective clinical observational study was to assess the feasibility and performance of the Narcotrend monitor in children <2 years within a clinical setting. METHODS: Sixty-one children aged 0-24 months undergoing general anesthesia with sevoflurane and remifentanil for elective pediatric surgery were studied. We investigated the percentage of differentiated electroencephalograms and the correlation between multiples of minimal alveolar sevoflurane concentration and the Narcotrend Index according to age groups. Prediction probability was used to evaluate the performance of the Narcotrend Index for differentiation between consciousness and unconsciousness and between different sevoflurane concentrations. RESULTS: The percentage of differentiated electroencephalograms increased with increasing age (0-3 months: 23.8%, 4-5 months: 87.5%, 6-11 months: 92.3%, 12-24 months: 100%). The overall prediction probability of Narcotrend Index was 1.0 (SE 0.05) for differentiation between awake and loss of consciousness and 1.0 (SE 0.01) for differentiation between anesthetized and return of consciousness. Spearman correlation analysis revealed a significant negative correlation between sevoflurane concentration and the Narcotrend Index (r = -0.78, P < .0001, 95%CI: -0.81 to -0.74). Overall prediction probability of Narcotrend Index to sevoflurane concentration was 0.8 (95%CI: 0.78-0.82). CONCLUSION: The Narcotrend monitor indicated a Narcotrend Index in most infants and young children starting from 4 months with significant correlation to and acceptable prediction probability for minimal alveolar sevoflurane concentration.

Optimization of initial propofol bolus dose for EEG Narcotrend Index-guided transition from sevoflurane induction to intravenous anesthesia in children.

BACKGROUND: Sevoflurane induction followed by intravenous anesthesia is a widely used technique to combine the benefits of an easier and less traumatic venipuncture after sevoflurane inhalation with a recovery with less agitation, nausea, and vomiting after total intravenous anesthesia (TIVA). Combination of two different anesthetics may lead to unwanted burst suppression in the electroencephalogram (EEG) during the transition phase. OBJECTIVE: The objective of this prospective clinical observational study was to identify the optimal initial propofol bolus dose for a smooth transition from sevoflurane induction to TIVA using the EEG Narcotrend Index (NI). METHODS: Fifty children aged 1-8 years scheduled for elective pediatric surgery were studied. After sevoflurane induction and establishing of an intravenous access, a propofol bolus dose range 0-5 mg·kg-1 was administered at the attending anesthetist's discretion to maintain a NI between 20 and 64, and sevoflurane was stopped. Anesthesia was continued as TIVA with a propofol infusion dose of 15 mg·kg-1 ·h-1 for the first 15 min, followed by stepwise reduction according to McFarlan's pediatric infusion regime, and remifentanil 0.25 µg·kg-1 ·min-1 . Endtidal concentration of sevoflurane, NI, and hemodynamic data were recorded during the whole study period using a standardized case report form. Propofol plasma concentrations were calculated using the paedfusor dataset and a TIVA simulation program. RESULTS: Median endtidal concentration of sevoflurane at the time of administration of the propofol bolus was 5.1 [IQR 4.7-5.9] Vol%. The median propofol bolus dose was 1.2 [IQR 0.9-2.5] mg·kg-1 and median NI thereafter was 33 [IQR 23-40]. Nine children presented with a NI 13-20 and three children with burst suppression in the EEG (NI 0-12); all of them received an initial propofol bolus dose >2 mg·kg-1 . Regression equation demonstrated that NI 20-64 was achieved with a 95% probability when using a propofol bolus dose of 1 mg·kg-1 after sevoflurane induction. Decrease in mean arterial blood pressure correlated significantly with propofol bolus dose (P = 0.038). After 25 min of TIVA, children younger than 2 years had a higher NI (median difference 14.0, 95%CI: 6.0-20.0, P = 0.001), higher deviations from the expected Narcotend Index (median difference 4.1, 95%CI: 3.9-4.2, P < 0.001) and lower calculated propofol plasma concentrations (median difference 0.2 µg·ml-1 , 95% CI: 0.1-0.3 µg·ml-1 , P < 0.001) than older children. CONCLUSION: After sevoflurane induction, a reduced propofol bolus dose of 1 mg·kg-1 followed by TIVA according to McFarlan's regime resulted in a NI within the recommended range in children aged 1-8 years. During the course of TIVA, children younger than 2 years displayed higher NI values and more pronounced interindividual variation. Processed EEG monitoring is recommended to find adequate individual age-dependent doses.

Compatibility of common drugs with acetate-containing balanced electrolyte solutions in pediatric anesthesia.

BACKGROUND: Acetate-containing balanced electrolyte solutions are frequently used for fluid therapy in pediatric anesthesia, but no studies investigating the compatibility with common anesthetic drugs are available. AIM: To reveal possible incompatibilities between common anesthetic drugs and the acetate-containing balanced electrolyte solutions BS (Sterofundin ISO; B.Braun Melsungen AG, Melsungen, Germany) and BS-G1 (E148G1 Päd; Serumwerk Bernburg AG, Bernburg, Germany), with normal saline (NS) as control. METHODS: All tested infusion solutions were mixed 1 : 1 with 28 common anesthetic drugs in concentrations used in daily clinical practice. Electrical conductivity, pH, and turbidimetric light diffusion at 405 nm were measured. Macroscopic changes such as gross precipitation, change in color, or bubble formation were also assessed. All measurements were performed immediately after mixing as well as 30 and 60 min after. RESULTS: The vast majority of drugs showed no significant change in pH, electric conductivity, turbidimetric detectable light diffusion, or macroscopic appearance after mixing with BS, BS-G1, and NS. Phenytoin immediately precipitated in response to all tested solutions as did diazepam. Thiopental precipitated after mixing with BS only. CONCLUSIONS: Most of the tested drugs did not show any signs or evidence of incompatibility reactions. However, phenytoin and diazepam should not be in contact with the three tested solutions, including NS. Thiopental should be used with caution because it can precipitate in solutions with a low pH (e.g., BS).

Impact of high doses of 6% hydroxyethyl starch 130/0.42 and 4% gelatin on renal function in a pediatric animal model.

OBJECTIVES: Despite serious renal side effects in critically ill adult patients, artificial colloids are still fundamental components of perioperative fluid therapy in infants and children, although the impact of 6% hydroxyethyl starch (HES) and 4% gelatin (GEL) on renal function during pediatric surgery has not been identified yet. AIM: To determine the impact of high doses of artificial colloids on renal function, we conducted an experimental animal study and hypothesized that neither the infusion of HES nor of GEL would have a serious impact on renal function. METHODS: Fifteen sedated piglets were randomly assigned to receive an infusion of either 50 ml · kg(-1) HES or GEL, or a balanced electrolyte solution (crystalloid group). Before and 1 week after infusion, serum and urine renal function tests were recorded and renal biopsies were taken. RESULTS: Serum and urine renal function tests revealed no increase after administration of HES and GEL, and only a discrete increase in serum creatinine (median 9.8 µmol · l(-1), 95% CI 4.0-19.1) in the crystalloid group. Histopathological examination indicated a sparsely, multifocal infiltration of mononuclear cells in all groups and an unspecific pyelectasia of one animal in the GEL group. CONCLUSIONS: After high doses of HES or GEL in piglets, no relevant impact on renal function could be found. These results confirm that AKI after HES or GEL is very unlikely in hemodynamically stable perioperative patients with normal renal function.

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.

BACKGROUND: Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers. METHODS: In a multi-centre study including seven European MH units, patients with a history of a clinical MH episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture tests (IVCT) were investigated. A test result is considered to be MHE if the muscle specimens develop pathological contractures in response to only one of the two test substances, halothane or caffeine. Crises were evaluated using a clinical grading scale (CGS), results of IVCT and genetic screening. The effects of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR) were studied in vitro. RESULTS: A total of 200 patients met the inclusion criteria. Two MH crises (1%) were triggered by SCh (1 MHS, 1 MHE), 18% by volatile anesthetics and 81% by a combination of both. Patients were 70% male and 50% were younger than 12 years old. Overall, CGS was in accord with IVCT results. Crises triggered by enflurane had a significantly higher CGS compared to halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1 variants, of which 14 were novel. CGS varied depending on the location of the mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not evoke Ca2+ release from isolated rat SR vesicles. CONCLUSIONS: An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.