Monitoring Depth of Hypnosis: Mid-Latency Auditory Evoked Potentials Derived aepEX in Children Receiving Desflurane-Remifentanil Anesthesia.

BACKGROUND: The aepEXplus monitoring system, which uses mid-latency auditory evoked potentials to measure depth of hypnosis, was evaluated in pediatric patients receiving desflurane-remifentanil anesthesia. METHODS: Seventy-five patients, 1-18 years of age (stratified for age; 1-3, 3-6, 6-18 years, for subgroup analyses), were included in this prospective observational study. The aepEX and the bispectral index (BIS) were recorded simultaneously, the latter serving as a reference. The ability of the aepEX to detect different levels of consciousness, defined according to the University of Michigan Sedation Scale, investigated using prediction probability (Pk), and receiver operating characteristic (ROC) analysis, served as the primary outcome parameter. As a secondary outcome parameter, the relationship between end-tidal desflurane and the aepEX and BIS values were calculated by fitting in a nonlinear regression model. RESULTS: The Pk values for the aepEX and the BIS were, respectively, .68 (95% CI, 0.53-0.82) and .85 (95% CI, 0.73-0.96; P = .02). The aepEX and the BIS had an area under the ROC curve of, respectively, 0.89 (95% CI, 0.80-0.95) and 0.76 (95% CI, 0.68-0.84; P = .04). The maximized sensitivity and specificity were, respectively, 81% (95% CI, 61%-93%) and 86% (95% CI, 74%-94%) for the aepEX at a cutoff value of >52, and 69% (95% CI, 56%-81%) and 70% (95% CI, 57%-81%) for the BIS at a cutoff value of >65. The age-corrected end-tidal desflurane concentration associated with an index value of 50 (EC50) was 0.59 minimum alveolar concentration (interquartile range: 0.38-0.85) and 0.58 minimum alveolar concentration (interquartile range: 0.41-0.70) for, respectively, the aepEX and BIS (P = .69). Age-group analysis showed no evidence of a difference regarding the area under the ROC curve or EC50. CONCLUSIONS: The aepEX can reliably differentiate between a conscious and an unconscious state in pediatric patients receiving desflurane-remifentanil anesthesia.

A practical approach to cerebral near-infrared spectroscopy (NIRS) directed hemodynamic management in noncardiac pediatric anesthesia.

Safeguarding cerebral function is of major importance during pediatric anesthesia. Premature, ex-premature, and full-term neonates can be vulnerable to physiological changes that occur during anesthesia and surgery. Data from studies performed during pediatric cardiac surgery and in neonatal/pediatric intensive care units have shown the benefits of near-infrared spectroscopy (NIRS) monitoring of regional cerebral oxygenation (c-rSO2 ). However, NIRS monitoring is seldom used during noncardiac pediatric anesthesia. Despite compelling evidence that blood pressure does not reflect end-organ perfusion, it is still regarded as the most important determinant of cerebral perfusion and the most relevant hemodynamic management target parameter by most (pediatric) anesthetists. The principle of NIRS monitoring is not self-explanatory and sometimes seems even counterintuitive, which may explain why many anesthesiologists are reserved regarding its use. The first part of this paper is dedicated to a clinical introduction to NIRS monitoring. Despite scientific efforts, it has not yet been possible to define individual lower limit c-rSO2 values and it is unlikely this will succeed in the near future. Nonetheless, published treatment algorithms usually specify c-rSO2 values which may be associated with cerebral hypoxia. Our treatment guideline for maintaining sufficient cerebral oxygenation differs fundamentally from all previously published approaches. We define a baseline c-rSO2 value, registered in the awake child prior to anesthesia induction, as the lowest acceptable limit during anesthesia and surgery. The cerebral rSO2 is the single target parameter, while blood pressure, heart rate, Pa CO2 , and SaO2 are major parameters that determine the c-rSO2. Cerebral NIRS monitoring, interpreted together with its continuously available contributing parameters, may help avoid potentially harmful episodes of cerebral desaturation in anesthetized pediatric patients.

Use, applicability and reliability of depth of hypnosis monitors in children - a survey among members of the European Society for Paediatric Anaesthesiology.

BACKGROUND: To assess the thoughts of practicing anaesthesiologists about the use of depth of hypnosis monitors in children. METHODS: Members of the European Society for Paediatric Anaesthesiology were invited to participate in an online survey about their thoughts regarding the use, applicability and reliability of hypnosis monitoring in children. RESULTS: The survey achieved a response rate of 30% (N = 168). A total of 138 completed surveys were included for further analysis. Sixty-eight respondents used hypnosis monitoring in children (Users) and 70 did not (Non-users). Sixty-five percent of the Users reported prevention of intra-operative awareness as their main reason to apply hypnosis monitoring. Among the Non-users, the most frequently given reason (43%) not to use hypnosis monitoring in children was the perceived lack or reliability of the devices in children. Hypnosis monitoring is used with a higher frequency during propofol anaesthesia than during inhalation anaesthesia. Hypnosis monitoring is furthermore used more frequently in children > 4 years than in younger children. An ideal hypnosis monitor should be reliable for all age groups and any (combination of) anaesthetic drug. We found no agreement in the interpretation of monitor index values and subsequent anaesthetic interventions following from it. CONCLUSIONS: Prevention of intraoperative awareness appears to be the most important reason to use hypnosis monitoring in children. The perceived lack of reliability of hypnosis monitoring in children is the most important reasons not to use it. No consensus currently exists on how to adjust anaesthesia according to hypnosis monitor index values in children.

The use of dipyrone (metamizol) as an analgesic in children: What is the evidence? A review.

Dipyrone has analgesic, spasmolytic, and antipyretic effects and is used to treat pain. Due to a possible risk of agranulocytosis with the use of dipyrone, it has been banned in a number of countries. The most commonly used data for the use of dipyrone are related to adults. Information relating to the use of dipyrone in children is scarce. Given the potential added value of dipyrone in the treatment of pain, a review of the literature was conducted to obtain more insight into the analgesic efficacy of dipyrone in children as well as the safety of dipyrone in terms of adverse events. A literature search was done for original articles (in English, German, or Spanish language) which met the following criteria: the use of dipyrone for pain and children up to the age of 17 years old. All titles and abstracts retrieved were reviewed, independently, by two of the authors, for their suitability for inclusion. The references of the selected articles were also checked for additional relevant papers. The publications were categorized into case reports, observational studies, or randomized controlled trials. To assess the methodological quality of the studies, the Jadad score was used. In the limited available data, the analgesic efficacy of intravenous dipyrone appears similar to that of intravenous paracetamol. Evidence is lacking to support the claim that dipyrone is equivalent or even superior to Non-Steroid-Anti-Inflammatory-Drugs in pediatric pain. While the absolute risk of agranulocytosis with dipyrone in children, based on available literature, cannot be determined, case reports suggest that this risk is not negligible.

Defining hypotension in anesthetized infants by individual awake blood pressure values: a prospective observational study.

BACKGROUND: Blood pressure (BP) is the most commonly applied clinical surrogate parameter for tissue perfusion and cerebral autoregulation. Hypotension during anesthesia may contribute to unfavorable outcome in young children. Hypotension in anesthetized infants can be defined using BP values relative to individual awake baseline or absolute BP values. AIM: The aim of this study was to investigate the applicability of the two definitions and to compare the incidences of hypotension. METHOD: This was a prospective observational study in 151 infants <12 months of age. The percentage of successful awake BP measurements was calculated and related to the infant's behavioral state. Hypotension under sevoflurane anesthesia was defined by a decrease of mean arterial pressure (MAP) relative to awake baseline (>20% in infants <6 months, >40% in infants >6 months) or absolute MAP values (<35 mmHg in infants <6 months, <43 mmHg in infants >6 months). The incidences of hypotension using the two definitions were compared. RESULTS: Awake BP values were obtained in 85% of the patients. Calm patients were more likely to allow their BP to be measured than anxious patients. Anxious patients had higher preinduction MAP values than calm patients. The relative BP approach resulted in a higher incidence of postinduction hypotension than using absolute BP values. CONCLUSIONS: Awake BP values were unobtainable in 15% of our patients, resulting in the necessity to define hypotension under anesthesia using absolute BP values. Definitions of hypotension using either absolute MAP or values relative to awake baseline are not interchangeable.

Arterial blood pressure in anesthetized neonates and infants: a retrospective analysis of 1091 cases.

BACKGROUND: Hypotension during general anesthesia in neonates and infants is considered to contribute to poor neurological outcome. AIM: The aim of this retrospective analysis was to determine the incidence of hypotension after induction of anesthesia and sustained hypotension (>10 min) during the anesthesia, and to determine factors contributing to the development of (sustained) hypotension. METHOD: We performed a retrospective analysis of 1091 electronic anesthesia records from children <1 year. Patients were stratified for age (group 1: <1 month, group 2: 1-3 months, group 3: 4-6 months, group 4: >6 months). Hypotension was defined as a mean arterial pressure (MAP) <35 mmHg in patients ≤6 months and <43 mmHg in patients >6 months. RESULTS: The incidence of hypotension after induction was highest in group 1 (25.5%) [P = 0.009 vs group 2 (13.3%), P < 0.0001 vs groups 3 (3.4%) and 4 (1.0%)], in group 2, it was higher than in groups 3 and 4 (P < 0.0001), and in group 3, it was higher than in group 4 (P = 0.033). The incidence of sustained hypotension was highest in group 1 (43.6%) (P < 0.0001 vs groups 2-4), followed by group 2 (15.7%) [P < 0.0001 vs group 3 (3.4%) and P = 0.006 vs group 4 (8.8%)] and group 4 (P = 0.004 vs group 3). Hypotension after induction occurred more often in emergency procedures than in elective procedures in groups 1 (P = 0.002), 2 (P = 0.029), and 3 (P = 0.037). CONCLUSION: Hypotension, both postinduction and sustained during surgery, is a common phenomenon in anesthetized children under 1 year, peaking in neonates. Generally accepted lower limits of MAP in anesthetized infants urgently need to be defined, enabling us to develop anesthesia strategies avoiding cerebral hypoperfusion.

Potential neurotoxicity of anesthetic drugs in young children: who cares? A survey among European anesthetists.

BACKGROUND: Potential neurotoxicity of anesthetic drugs is currently one of the most intensely discussed issues in pediatric anesthesia. Prospective human data are sorely lacking and there is an on-going debate among experts in the field whether one should (or can) extrapolate animal data to humans. Data regarding the thoughts of practicing anesthetists regarding this topic have not been published. METHODS: A web-based survey to assess the thoughts of practicing (European) anesthetists regarding neurotoxicity and how it may have influenced their daily practice of pediatric anesthesia. RESULTS: The majority (68.7%) of respondents regard neurotoxicity as an important topic, which they need to further explore. Two thirds have already changed their clinical practice and 44.3% were concerned about potential neurotoxicity. Anesthetists from children's hospitals were less likely to routinely inform parents about neurotoxicity (P=0.005) and more often applied an opioid-only anesthesia technique in selected premature neonates than general hospital based anesthetists (P<0.0001). Prospective human longitudinal studies focusing on neurodevelopment were given the highest priority for future research, whereas animal studies scored lowest. CONCLUSIONS: Practicing anesthetists care about potential neurotoxicity of anesthetic drugs in young children. Colleagues working in children's hospital have slightly different attitudes to deal with the topic, compared to those working in general hospitals. The vast majority of our colleagues are waiting for prospective human research data that may help to unravel the current controversy surrounding potential anesthetic drug neurotoxicity and help to improve the safety of pediatric anesthesia.

Evaluation of the auditory evoked potentials derived aepEX(™) as a measure of hypnotic depth in pediatric patients receiving sevoflurane-remifentanil anesthesia.

BACKGROUND: The aepEX is a measure of depth of hypnosis (DoH), derived from processed mid-latency auditory evoked potentials. OBJECTIVES: To evaluate the aepEX as a measure of DoH in children receiving sevoflurane-remifentanil anesthesia. METHODS: aepEX and bispectral index (BIS) were recorded simultaneously in 75 children, (1-3, 3-6, and 6-18 years), receiving sevoflurane at endtidal concentrations (ETsevo ) between 1.5 and 0.5 MAC. The ETsevo at which the aepEX and BIS had a value of 50 (EC50aep EX and EC50BIS ) was calculated by nonlinear regression analysis. The accuracy of aepEX and BIS to predict the DoH was assessed by prediction probability (Pk ) and receiver operating characteristics (ROC) analysis. RESULTS: Seventy-four children were included for analysis. The EC50aep EX (2.68%) and EC50BIS (2.10%) were comparable; the same accounts for the EC50aep EX of the different age groups and the EC50aep EX and EC50BIS of corresponding age groups. The EC50BIS in children aged 1-3 years was lower than in the older age groups (P < 0.05). Pk values of the aepEX (0.32, CI 95% 0.08-0.56) and BIS (0.47, CI 95% 0.19-0.75) were comparable. The area under the ROC curve was 0.72 (CI 95%: 0.62-0.82) and 0.67 (CI95%: 0.56-0.77) for the aepEX and BIS, respectively (P = 0.54). Optimal cutoff values were >60 (aepEX) and >68 (BIS), with corresponding specificities 91%, CI 95%: 80-97% (aepEX) and 66%, CI 95%: 52-77% (BIS). CONCLUSIONS: In this study with children receiving sevoflurane anesthesia, the aepEX outperformed the BIS in distinguishing unconsciousness from consciousness. Both indices performed equally bad in differentiating different levels of DoH.

Evaluation of the aepEX™ monitor of hypnotic depth in pediatric patients receiving propofol-remifentanil anesthesia.

BACKGROUND: The aepEX Plus monitor (aepEX) utilizes a mid-latency auditory evoked potential-derived index of depth of hypnosis (DoH). OBJECTIVE: This observational study evaluates the performance of the aepEX as a DoH monitor for pediatric patients receiving propofol-remifentanil anesthesia. METHODS: aepEX and BIS values were recorded simultaneously during surgery in three groups of 25 children (aged 1-3, 3-6 and 6-16 years). Propofol was administered by target-controlled infusion. The University of Michigan Sedation Scale (UMSS) was used to clinically assess the DoH during emergence. Prediction probability (P(k)) and receiver operating characteristics (ROC) analyses were performed to assess the accuracy of both DoH monitors. Nonlinear regression analysis was used to describe the dose-response relationships for the aepEX, the BIS, and propofol plasma concentrations (Cp). RESULTS: The P(k) for the aepEX and BIS was 0.36 and 0.21, respectively (P = 0.010). ROC analysis showed an area under the curve of 0.77 and 0.88 for the aepEX and BIS, respectively (P = 0.644). At half-maximal effect (EC(50)), C(p) of 3.13 µg·ml(-1) and 3.06 µg·ml(-1) were observed for the aepEX and BIS, respectively. The r(2) for the aepEX and BIS was 0.53 and 0.82, respectively. CONCLUSION: The aepEX performs comparable to the BIS in differentiating between consciousness and unconsciousness, while performing inferior to the BIS in terms of distinguishing different levels of sedation and does not correlate well with the C(p) in children receiving propofol-remifentanil anesthesia.