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Nirmeen Fayed,1,2 Sally Waheed Elkhadry,3 Andreas Garling,1 Richard K Ellerkmann1,4 1Anethesia and Critical Care Department, Klinikum Dortmund, Dortmund, Germany; 2Anesthesia and Critical Care Department, National Liver Institute Menoufia University, Shebin-Alkoom, Egypt; 3Epidemiology and Preventive Medicine Institute, National Liver Institute, Menoufia University, Shebin-Alkoom, Egypt; 4Anesthesia and Critical Care Department, Bonn University, Bonn, GermanyCorrespondence: Nirmeen Fayed, Anesthesia Department Klinikum Dortmund, Germany, Mollwitzer Straße 4, Dortmund, 44141, Germany, Tel +49 17647154842, Email drnirmeena@yahoo.comBackground: The Revised Cardiac Risk Index (RCRI) and the Geriatric Sensitive Cardiac Risk Index (GSCRI) estimate the risk of postoperative major adverse cardiac events (MACE) regardless of the type of anesthesia and without specifying the oldest old patients. Since spinal anesthesia (SA) is a preferred technique in geriatrics, we aimed to test the external validity of these indices in patients ≥ 80 years old who underwent surgery under SA and tried to identify other potential risk factors for postoperative MACE.Methods: The performance of both indices to estimate postoperative in-hospital MACE risk was tested through discrimination, calibration, and clinical utility. We also investigated the correlation between both indices and postoperative ICU admission and length of hospital stay (LOS).Results: The MACE incidence was 7.5%. Both indices had limited discriminative (AUC for RCRI and GSCRI were 0.69 and 0.68, respectively) and predictive abilities. The regression analysis showed that patients with atrial fibrillation (AF) were 3.77 and those with trauma surgery were 2.03 times more likely to exhibit MACE, and the odds of MACE increased by 9% for each additional year above 80. Introducing these factors into both indices (multivariable models) increased the discriminative ability (AUC reached 0.798 and 0.777 for RCRI and GSCRI, respectively). Bootstrap analysis showed that the predictive ability of the multivariate GSCRI but not the multivariate RCRI improved. Decision curve analysis (DCA) showed that multivariate GSCRI had superior clinical utility when compared with multivariate RCRI. Both indices correlated poorly with postoperative ICU admission and LOS.Conclusion: Both indices had limited predictive and discriminative ability to estimate postoperative in-hospital MACE risk and correlated poorly with postoperative ICU admission and LOS, following surgery under SA in the oldest-old patients. Updated versions by introducing age, AF, and trauma surgery improved the GSCRI performance but not the RCRI.Keywords: geriatric, anesthetic techniques, subarachnoid, risk, major adverse cardiac event

This study was designed to investigate the impact of the Entropy Module and Bispectral Index (BIS) monitoring on drug consumption and recovery times compared with standard anaesthetic practice in patients undergoing orthopaedic surgery using a combination of regional and general anaesthesia as performed by an experienced anaesthesiologist. We hypothesised that electroencephalogram monitoring would lead to a lower drug consumption as well as shorter recovery times. With institutional review board approval and written informed consent, 90 adult patients undergoing surgery to the upper or lower extremity received regional anaesthesia for post- and intraoperative pain control and were randomised to receive general anaesthesia by propofol/remifentanil infusion controlled either solely by clinical parameters or by targeting Entropy or BIS values of 50. Recovery times and drug consumption were recorded. Data from 79 patients were analysed. Compared with standard practice, patients with Entropy or BIS monitoring showed a similar propofol consumption (standard practice 101 +/- 22 microg/kg/minute, Entropy 106 +/- 24 microg/kg/minute, BIS 104 +/- 20 microg/kg/minute) and showed similar Aldrete scores (10/10) one minute after extubation: 9.1 +/- 0.3, 9.2 +/- 0.6 and 9.3 +/- 0.5, respectively. Time points of extubation were 7.3 +/- 2.9 minutes, 9.2 +/- 3.9 minutes and 6.8 +/- 2.9 minutes, respectively, demonstrating a significant difference between Entropy and BIS (P = 0.023). Compared with standard practice, targeting an Entropy or BIS value of 50 did not result in a reduction of propofol consumption during general anaesthesia combined with regional anaesthesia as performed by an experienced anaesthesiologist in orthopaedic patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: The Bispectral Index (BIS) and the Patient State Index (PSI) quantify depth of anesthesia by analyzing the electroencephalogram. The authors examined the response of BIS and PSI to sevoflurane anesthesia. METHODS: In 22 patients, sevoflurane anesthesia was induced by inhalation with a tight-fitting facemask and was maintained via a laryngeal mask. Sevoflurane concentrations were increased until burst suppression occurred and subsequently decreased until BIS recovered to values above 60. This procedure was repeated twice until patients underwent intubation for subsequent surgery. End-tidal sevoflurane concentrations, BIS, and PSI were recorded simultaneously. The performance of PSI and BIS to predict the estimated sevoflurane effect site concentration, as derived from simultaneous pharmacokinetic and pharmacodynamic modeling, was compared by determination coefficients (rho(2)) and prediction probabilities (P(K)). RESULTS: A significant (P < 0.001) correlation between BIS and PSI was found (r(2) = 0.75), and a close sigmoid relation between sevoflurane effect site concentration and both BIS (rho(2) = 0.84 +/- 0.09) and PSI (rho(2) = 0.85 +/- 0.15) was observed. The maximum sevoflurane electroencephalographic effect resulted in PSI values (1.3 +/- 4.3) that were significantly (P = 0.019) lower than BIS values (7.9 +/- 12.1), and the effect site efflux constant k(e0) was significantly smaller (P = 0.001) for PSI (0.13 +/- 0.08 min(-1)) than for BIS (0.24 +/- 0.15 min(-1)). The probability of BIS (P(K) = 0.80 +/- 0.11) to predict sevoflurane effect site concentration did not differ (P = 0.76) from that of PSI (P(K) = 0.79 +/- 0.09). CONCLUSIONS: The BIS reacted faster to changes in sevoflurane concentrations, whereas the PSI made better use of the predefined index range. However, despite major differences in their algorithms and minor differences in their dose-response relations, both PSI and BIS predicted depth of sevoflurane anesthesia equally well. [ABSTRACT FROM AUTHOR]

Background: The aim of this prospective multicenter observational study was to measure the incidence of postoperative pediatric emergence delirium and to investigate the occurrence of early postoperative negative behavior within two weeks after outpatient adenoidectomy in preschool children., Methods: The study comprised 222 patients (1...7 years of age). All children received a multimodal anesthesia based on total intravenous anesthesia with propofol and remifentanil in combination with piritramid (0.1 mg.kg -1 ), ibuprofen (10 mg.kg -1 ), dexamethason (0.15 mg.kg -1 ), and ketanest S (0.1 mg.kg -1 ). We evaluated emergence delirium using the Pediatric Anesthesia Emergence Delirium Scale (PAED) at different predefined time points during the recovery period. Emergence delirium was defined as a PAED score ... 9 for the first three criteria. Additionally, we defined early postoperative negative behavior to be present when at least 5 of 27 criteria of the post hospitalization behavior questionnaire were positive., Results: The incidence of emergence delirium following our anesthetic regime was 23%. The incidence of early postoperative negative behavior was significantly higher among patients with emergence delirium (24% vs. 11%, p = 0.04). The two categories, ..úsleep disturbance..Ñ and ..úseparation anxiety..Ñ, tested within the questionnaire for early postoperative negative behavior, were identified as the most common postoperative negative behavioral changes., Conclusion: Emergence delirium not only plays a role immediately after surgery but is also linked to early postoperative negative behavior within two weeks after outpatient adenoidectomy. Parents should be informed that early postoperative negative behavior may occur in 1 out of 4 patients if emergence delirium was present postoperatively., Trial Registration: DRKS ... German Clinical Trial Register ID: DRKS00013121., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Near Infrared Spectroscopy (NIRS) has become widely accepted to evaluate regional cerebral oxygen saturation (rScO2), potentially acting as a surrogate parameter of reduced cerebral oxygen delivery or increased consumption. Low preoperative rScO2 is associated with increased postoperative complications after cardiac surgery. However, its universal potential in pre-anesthesia risk assessment remains unclear. Therefore, we investigated whether low preoperative rScO2 is indicative of postoperative complications and associated with poor outcomes in noncardiac surgical patients. We prospectively enrolled 130 patients undergoing high-risk noncardiac surgery. During pre-anesthesia evaluation, baseline rScO2 was recorded with and without oxygen supplementation. The primary endpoint was 30-day mortality, while secondary endpoints were postoperative myocardial injury, respiratory complications, and renal failure. We further evaluated the impact of body position and preoperative hemoglobin (Hb) concentration on rScO2. Of the initially enrolled 130 patients, 126 remained for final analysis. Six (4.76%) patients died within 30 postoperative days. 95 (75.4%) patients were admitted to the ICU. 32 (25.4%) patients suffered from major postoperative complications. There was no significant association between rScO2 and 30-day mortality or secondary endpoints. Oxygen supplementation induced a significant increase of rScO2. Furthermore, Hb concentration correlated with rScO2 values and body position affected rScO2. No significant association between rScO2 values and NYHA, LVEF, or MET classes were observed. Preoperative rScO2 is not associated with postoperative complications in patients undergoing high-risk noncardiac surgery. We speculate that the discriminatory power of NIRS is insufficient due to individual variability of rScO2 values and confounding factors., (© 2023. The Author(s).)

This is a case report of a 45-year-old patient, 39 weeks of gestation, who was intubated via rapid sequence induction (RSI) for an emergency cesarean. The indication for emergency cesarean was a pathological cardiotocography during the ejection phase following labor induction.Despite the primary use of a video laryngoscope, there was difficulty aligning the laryngeal axis. Therefore, an internal stylet was used to heavily angulate the endotracheal tube (ETT) to a hockey stick shape to enter the larynx.Postoperative dyspnea and extensive facial swelling were initially diagnosed as an allergic reaction. Only 22 h later the diagnosis of tracheal rupture was confirmed following computer tomography.We hypothesized that the mechanism of injury was due to excessive pressure transmitted to the tip of the ETT. This probably occurred due to a leverage effect caused by the withdrawal of the heavily bent stylet from the ETT, forcing an intratracheal cranial movement of the ETT.By conducting an experiment on a pig's trachea, we were able to visualize this mechanism of injury. In addition, we were able to demonstrate that bending the stylet to a similar angle as the laryngoscope blade led to minimal movement of the tip of the ETT.Therefore, when using a stylet during intubation, we recommend bending the ETT and stylet to the shape of the used laryngoscope blade and retracting the stylet at a similar angle to avoid complications, such as tracheal rupture., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background: Severe COVID-19 induced acute respiratory distress syndrome (ARDS) often requires extracorporeal membrane oxygenation (ECMO). Recent German health insurance data revealed low ICU survival rates. Patient characteristics and experience of the ECMO center may determine intensive care unit (ICU) survival. The current study aimed to identify factors affecting ICU survival of COVID-19 ECMO patients., Methods: 673 COVID-19 ARDS ECMO patients treated in 26 centers between January 1st 2020 and March 22nd 2021 were included. Data on clinical characteristics, adjunct therapies, complications, and outcome were documented. Block wise logistic regression analysis was applied to identify variables associated with ICU-survival., Results: Most patients were between 50 and 70 years of age. PaO 2 /FiO 2 ratio prior to ECMO was 72 mmHg (IQR: 58-99). ICU survival was 31.4%. Survival was significantly lower during the 2nd wave of the COVID-19 pandemic. A subgroup of 284 (42%) patients fulfilling modified EOLIA criteria had a higher survival (38%) (p = 0.0014, OR 0.64 (CI 0.41-0.99)). Survival differed between low, intermediate, and high-volume centers with 20%, 30%, and 38%, respectively (p = 0.0024). Treatment in high volume centers resulted in an odds ratio of 0.55 (CI 0.28-1.02) compared to low volume centers. Additional factors associated with survival were younger age, shorter time between intubation and ECMO initiation, BMI > 35 (compared to < 25), absence of renal replacement therapy or major bleeding/thromboembolic events., Conclusions: Structural and patient-related factors, including age, comorbidities and ECMO case volume, determined the survival of COVID-19 ECMO. These factors combined with a more liberal ECMO indication during the 2nd wave may explain the reasonably overall low survival rate. Careful selection of patients and treatment in high volume ECMO centers was associated with higher odds of ICU survival., Trial Registration: Registered in the German Clinical Trials Register (study ID: DRKS00022964, retrospectively registered, September 7th 2020, https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00022964 ., (© 2022. The Author(s).)

Importance: Intraoperative handovers of anesthesia care are common. Handovers might improve care by reducing physician fatigue, but there is also an inherent risk of losing critical information. Large observational analyses report associations between handover of anesthesia care and adverse events, including higher mortality., Objective: To determine the effect of handovers of anesthesia care on postoperative morbidity and mortality., Design, Setting, and Participants: This was a parallel-group, randomized clinical trial conducted in 12 German centers with patients enrolled between June 2019 and June 2021 (final follow-up, July 31, 2021). Eligible participants had an American Society of Anesthesiologists physical status 3 or 4 and were scheduled for major inpatient surgery expected to last at least 2 hours., Interventions: A total of 1817 participants were randomized to receive either a complete handover to receive anesthesia care by another clinician (n = 908) or no handover of anesthesia care (n = 909). None of the participating institutions used a standardized handover protocol., Main Outcomes and Measures: The primary outcome was a 30-day composite of all-cause mortality, hospital readmission, or serious postoperative complications. There were 19 secondary outcomes, including the components of the primary composite, along with intensive care unit and hospital lengths of stay., Results: Among 1817 randomized patients, 1772 (98%; mean age, 66 [SD, 12] years; 997 men [56%]; and 1717 [97%] with an American Society of Anesthesiologists physical status of 3) completed the trial. The median total duration of anesthesia was 267 minutes (IQR, 206-351 minutes), and the median time from start of anesthesia to first handover was 144 minutes in the handover group (IQR, 105-213 minutes). The composite primary outcome occurred in 268 of 891 patients (30%) in the handover group and in 284 of 881 (33%) in the no handover group (absolute risk difference [RD], -2.5%; 95% CI, -6.8% to 1.9%; odds ratio [OR], 0.89; 95% CI, 0.72 to 1.10; P = .27). Nineteen of 889 patients (2.1%) in the handover group and 30 of 873 (3.4%) in the no handover group experienced all-cause 30-day mortality (absolute RD, -1.3%; 95% CI, -2.8% to 0.2%; OR, 0.61; 95% CI, 0.34 to 1.10; P = .11); 115 of 888 (13%) vs 136 of 872 (16%) were readmitted to the hospital (absolute RD, -2.7%; 95% CI, -5.9% to 0.6%; OR, 0.80; 95% CI, 0.61 to 1.05; P = .12); and 195 of 890 (22%) vs 189 of 874 (22%) experienced serious postoperative complications (absolute RD, 0.3%; 95% CI, -3.6% to 4.1%; odds ratio, 1.02; 95% CI, 0.81 to 1.28; P = .91). None of the 19 prespecified secondary end points differed significantly., Conclusions and Relevance: Among adults undergoing extended surgical procedures, there was no significant difference between the patients randomized to receive handover of anesthesia care from one clinician to another, compared with the no handover group, in the composite primary outcome of mortality, readmission, or serious postoperative complications within 30 days., Trial Registration: ClinicalTrials.gov Identifier: NCT04016454.

Background: Pediatric emergence delirium is characterized by a disturbance of a child's awareness during the early postoperative period that manifests as disorientation, altered attention and perception. The incidence of emergence delirium varies between 18% and 80% depending on risk factors and how it is measured. Reports from Canada, Germany, Italy, United Kingdom, and France demonstrated a wide range of preventive measures and definitions, indicating that there is a lack of clarity regarding emergence delirium. We aimed to assess the practices and beliefs among Brazilian anesthesiologists regarding emergence delirium., Methods: A web-based survey was developed using REDCap®. A link and QR Code were sent by email to all Brazilian anesthesiologists associated with the Brazilian Society of Anesthesiology (SBA)., Results: We collected 671 completed questionnaires. The majority of respondents (97%) considered emergence delirium a relevant adverse event. Thirty-two percent of respondents reported routinely administrating medication to prevent emergence delirium, with clonidine (16%) and propofol (15%) being the most commonly prescribed medications. More than 70% of respondents reported a high level of patient and parent anxiety, a previous history of emergence delirium, and untreated pain as risk factors for emergence delirium. Regarding treatment, thirty-five percent of respondents reported using propofol, followed by midazolam (26%)., Conclusion: Although most respondents considered emergence delirium a relevant adverse event, only one-third of them routinely applied preventive measures. Clonidine and propofol were the first choices for pharmacological prevention. For treatment, propofol and midazolam were the most commonly prescribed medications., (Copyright © 2021 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.)

Vitally essential red fluids like packed cells and red wine are seriously influenced in quality when stored over prolonged periods. In the case of red cell concentrates, the resulting storage lesion has particular significance in perioperative medicine. We hypothesized that, in contrast, aging rather improves the properties of red wine in several ways. A translational approach, including (I) in vitro experiments, (II) a randomized, blinded crossover trial of acute clinical effects, and (III) a standardized red wine blind tasting was used. Three monovarietal wines (Cabernet Sauvignon, Chianti, Shiraz) in three different vintages (range 2004-2016), each 5 years different, were assessed. Assessments were performed at a German university hospital (I, II) and on a garden terrace during a mild summer evening (III). Young wines induced cell stress and damage while significantly reducing cytoprotective proteins in HepG2 hepatoma cells. Sympathetic activity and multitasking skills were altered depending on wines' ages. Hangovers tended to be aggravated by young red wine. Aged variants performed better in terms of aroma and overall quality but worse in optical appearance. We found no evidence for a red wine storage lesion . However, we plead for consensus-based guidelines for proper storage, as it is common in clinical medicine., Competing Interests: Conflict of interest: The authors state no conflict of interest., (© 2021 Sven Klaschik et al., published by De Gruyter.)

This is a case report of a 29-year-old female patient who developed unilateral mydriasis following the use of a scopolamine patch for the prevention of postoperative nausea and vomiting (PONV).Given a medical history showing multiple risk factors for PONV, a preauricular scopolamine patch was applied prior to the induction of anesthesia. General anesthesia was induced with 150 mg propofol and 25 μg sufentanil and maintained with total intravenous anesthesia, using propofol (5 mg/kg per h) and remifentanil (2-3 μg/kg per h).Following an uneventful surgery of 90min duration, the patient was extubated and transferred to the recovery room, where the patch was removed. During the orthopedic ward round the following day, the clinical examination revealed anisocoria of the left eye in the form of unilateral mydriasis. In order to determine the cause of this clinical presentation, further neurological and ophthalmological examinations and investigations were carried out. In addition, magnetic resonance imaging was conducted to rule out a central nervous cause. The results of the investigations were negative and no pathology was identified. In addition, the symptoms resolved within 24 h of onset without any therapeutic intervention. Therefore, a suspected diagnosis of a pharmacologically induced anisocoria from the scopolamine patch was made, whereby the substance accidentally reached the affected left eye.Previous studies showed that scopolamine patches may reduce early emetic symptoms. Case reports describing the occurrence of anisocoria following the application of scopolamine patches have been previously published. In all of these cases the patches were used to prevent PONV and each case was comprehensively investigated using various diagnostic and clinical tools. It should be noted, however, that a dysfunctional accommodation is listed as a common side effect of the drug, affecting more than 1 in 10 patients.Even though the efficacy of scopolamine patches for the prevention of PONV is proven, clinicians should be aware of the common ophthalmological side effect. Particularly with respect to various surgical disciplines, where anisocoria may indicate an underlying surgery-related complication, the application of scopolamine patches should be well- considered.

Introduction: Oncological head and neck operations as well as carotid endarterectomy are common surgical procedures. In some occasions, both procedures have occurred in the past, leading to possible diagnostic and therapeutic challenges when follow-up operations seem indicated., Case Report: We report of a patient presenting with carotid endarterectomy including patch operation 8 years ago and neck dissection due to a squamous cell cancer of the tongue 3 months ago, now showing up with a suspected metastatic tumor of the neck during routine follow-up. Intraoperatively, nearly fatal bleeding occurs due to a partial release of the carotid patch and needs to be managed immediately., Discussion: The primarily pre-operated neck remains challenging for the radiologist in terms of differentiating between chronic lymphadenitis and metastasis. Furthermore, it remains challenging for the oncological surgeon in case these entities are in the near proximity of the previously operated carotid artery. The operative treatment according to the guidelines can lead to major bleeding during the second surgery. During the diagnostic process, metastases and chronic lymphadenitis after alloplastic carotid operations must be differentiated remaining however difficult, due to only scarce data in the literature., Conclusion: In the case of previous neck surgery, the decision to operate must be chosen individually regarding the specific conditions and their sometimes vital risks. In case an operation is indicated, the team must be trained to treat life-threatening intraoperative bleeding. In reviewing the literature, we were unable to find published recommendations on how to tackle these challenges.

Background: Our objective was to evaluate if changes in on-pump cerebral blood flow, relative to the pre-bypass baseline, are associated with the risk for postoperative delirium (POD) following cardiac surgery., Methods: In 47 consecutive adult patients, right middle cerebral artery blood flow velocity (MCAV) was assessed using transcranial Doppler sonography. Individual values, measured during cardiopulmonary bypass (CPB), were normalized to the pre-bypass baseline value and termed MCAV rel . An MCAV rel  > 100% was defined as cerebral hyperperfusion. Prevalence of POD was assessed using the Confusion Assessment Method for the Intensive Care Unit., Results: Overall prevalence of POD was 27%. In the subgroup without POD, 32% of patients had experienced relative cerebral hyperperfusion during CPB, compared to 67% in the subgroup with POD (p < 0.05). The mean averaged MCAV rel was 90 (±21) % in the no-POD group vs. 112 (±32) % in the POD group (p < 0.05), and patients developing delirium experienced cerebral hyperperfusion during CPB for about 39 (±35) min, compared to 6 (±11) min in the group without POD (p < 0.001). In a subcohort with pre-bypass baseline MCAV (MCAV bas ) below the median MCAV bas of the whole cohort, prevalence of POD was 17% when MCAV rel during CPB was kept below 100%, but increased to 53% when these patients actually experienced relative cerebral hyperperfusion., Conclusions: Our results suggest a critical role for cerebral hyperperfusion in the pathogenesis of POD following on-pump open-heart surgery, recommending a more individualized hemodynamic management, especially in the population at risk.

Introduction: General anaesthesia (GA) during mechanical thrombectomy (MT) might lead to an inferior clinical outcome compared to conscious sedation (CS). It was hypothesised that using CS might avoid a critical drop in cerebral perfusion, shorten the time of the intervention and therefore might result in better clinical outcome. In this study, we compared the procedural and clinical results of patients who underwent MT under GA or CS at two tertiary neuro-vascular centres on the basis of a matched-pair analysis., Methods: Using a matched-pair approach, we compared the data of 56 patients that were treated under CS at centre A (n = 28) with selected patients who were treated under GA at the centre B (n = 28). Patients were matched for age, sex, site of vessel occlusion, NIHSS at admission (±3 points), time from symptom onset to initial stroke imaging, intravenous-lysis and co-morbidities. All patients had an ASPECT-score of ≥8. To exclude the effect of technical failures, only patients with successful recanalization of the occluded vessel (TICI 2b and 3) were included into the study. The primary endpoint was the proportion of patients with early good clinical outcome after MT, defined by a modified Ranking Scale (mRS)-score ≤2 at discharge. Secondary endpoints were the time from symptom onset to the start of the procedure, the duration of the procedure and the rate of procedural complications., Results: There were no differences concerning gender, age, the site of vessel occlusion and the degree of stroke severity at baseline. The proportion of patients with an early good clinical outcome (mRS ≤2 at discharge) was 60.4% (17/28) in both groups. The time from symptom onset to the start of the procedure was shorter at centre B, while the duration of the procedure was significantly faster at A, resulting in an overall time from symptom onset to complete recanalization of 152.2 ± 68.0 min for patients treated at centre A and 171.1 ± 43.5 min for patients at centre B (ns)., Conclusion: Our study revealed no differences in the investigated clinical outcome for patients undergoing endovascular stroke treatment under GA versus CS., (© 2019 S. Karger AG, Basel.)

The upcoming and ongoing debate on neurotoxicity of anesthetics at a young age put a new spotlight on the emergence delirium of children (paedED). The European Society for Anesthesiology published a consensus guideline on prevention and therapy in 2017 which can be a useful guidance in daily clinical practice. Patient data management systems with their clear documentation concerning pain/therapy of pain and paedED will be valuable tools in order to assess the real incidence of paedED. Differentiating between pain/agitation and paedED migth not always be easy. Age-adapted scores should always be applied. Main focus in the prevention of paedED is the reduction of anxiety. The way this is achieved by the dedicated pediatric anesthesia teams caring for children, e.g. by oral midazolam, clowns, music, smartphone induction, does not matter. Using α 2 -agonists in the perioperative phase and applying propofol seems to be effective. A quiet supportive environment for recovery adds to a relaxed, stress-free awakening. For the future detecting paedED on normal wards becomes an important issue. This may be achieved by structured interviews or questionnaires assessing postoperative negative behavioural changes at the same time., Competing Interests: Die Autoren geben an, dass keine Interessenkonflikte vorliegen., (Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: In clinical practice, using different opioid analgesics is common during the induction and maintenance of general anesthesia and for postoperative analgesia. However, if the opioid analgesic could be limited to a single drug, we hypothesized that the risk of adverse drug interactions could be reduced, with fewer adverse effects. We examined the use of oxycodone as a single opioid in a well-defined cohort of orthopedic patients undergoing general anesthesia., Methods: In this retrolective, monocentric investigation, we reviewed data from 83 patients who underwent general anesthesia and received intravenous oxycodone as the sole analgesic (0.075 mg/kg during induction and 0.05 mg/kg during maintenance). The use of oxycodone during general anesthesia and the postoperative pain scores were recorded. Safety was evaluated by the measurement of hemodynamic changes (blood pressure, heart rate), the detection of pathologic changes in the electrocardiogram, changes of the peripheral oxygen saturation, and by the assessment of adverse effects., Results: There was no significant change in peripheral oxygen saturation or the electrocardiogram during or while recovering from general anesthesia. Heart rate changed only slightly from reversal to recovery (73.3/min versus 78.3/min, p < 0.05) and from prior intubation to recovery (72.5/min versus 78.3/min, p < 0.05). Systolic and diastolic blood pressure did not change significantly from the time points "after intubation" to "after incision," and "during recovery." Fifty-nine percent (n = 49) of patients' records revealed pain scores with a maximum of 3 on a numeric rating scale (NRS) of 0 to10 during the postoperative period. In 45 percent of patients (n = 37), further analgesics such as acetaminophen, dipyrone, or additional doses of oxycodone were used. No severe adverse events were recorded. According to data from 93 percent of patients (n = 77), nausea scores were less than 3 on a NRS of 0 to 10., Conclusion: Oxycodone can be used as the sole opioid in orthopedic surgery with good intra- and postoperative efficacy and safety; ie, without clinically relevant changes in hemodynamic and respiratory parameters.

Background: Postoperative neurological injury still represents a major cause of morbidity after cardiac surgery. Our objective was to compare the limits as well as advantages of routine monitoring tools for the detection of cerebral function and perfusion deficits during cardiopulmonary bypass in a daily clinical setting., Methods: Adult patients undergoing elective cardiac surgery with use of cardiopulmonary bypass were included. Patients received monitoring comprising Bispectral Index (BIS), Near Infrared Spectroscopy (NIRS) and assessment of middle cerebral artery flow velocity (MCAV) using transcranial Doppler (TCD) sonography. Measurements were taken after anesthesia induction (at baseline) and every 10 minutes during aortic cross-clamping. Relative deviation from baseline values was calculated. Values were compared with predefined, generally accepted threshold values identifying patients at risk for cerebral functional and perfusion deficits., Results: 30 consecutive patients were included into data analysis. Compared to NIRS as well as BIS monitoring, there was a wide interindividual variability in relative MCAV values for the whole cohort (median 0.9, range 0.39-2.19). Out of 229 measurements in total, 82 BIS but only 30 NIRS and 12 TCD values were lying outside predefined limits. TCD monitoring identified two patients with disturbed cerebral autoregulation, while NIRS remained unremarkable. The latter was significantly associated with systemic hemoglobin levels. Finally, patients with relative MCAV values >1.0 had a higher risk of developing postoperative delirium., Conclusion: Our findings reveal inherent technical limitations of each individual monitoring component, such as high interindividual variability (TCD), low spatial resolution (NIRS), or interaction with anesthetics (BIS). We therefore argue for a multimodal neuromonitoring that combines several qualities. Such approach would help reducing these limitations while individual components complement each other, thus providing more patient safety during cardiac surgery. Furthermore, such an approach would be easily applicable in a routine clinical setting.

Background: During awake craniotomy, the patient's language centers are identified by neurological testing requiring a fully awake and cooperative patient. Hence, anesthesia aims for an unconscious patient at the beginning and end of surgery but an awake and responsive patient in between. We investigated the plasma (Cplasma) and effect-site (Ceffect-site) propofol concentration as well as the related Bispectral Index (BIS) required for intraoperative return of consciousness and begin of neurological testing., Materials and Methods: In 13 patients, arterial Cplasma were measured by high-pressure liquid chromatography and Ceffect-site was estimated based on the Marsh and Schnider pharmacokinetic/dynamic (pk/pd) models. The BIS, Cplasma and Ceffect-site were compared during the intraoperative awakening period at designated time points such as return of consciousness and start of the Boston Naming Test (neurological test)., Results: Return of consciousness occurred at a BIS of 77±7 (mean±SD) and a measured Cplasma of 1.2±0.4 μg/mL. The Marsh model predicted a significantly (P<0.001) higher Cplasma of 1.9±0.4 µg/mL as compared with the Schnider model (Cplasma=1.4±0.4 µg/mL) at return of consciousness. Neurological testing was possible as soon as the BIS had increased to 92±6 and measured Cplasma had decreased to 0.8±0.3 µg/mL. This translated into a time delay of 23±12 minutes between return of consciousness and begin of neurological testing. At begin of neurological testing, Cplasma according to Marsh (Cplasma=1.3±0.5 µg/mL) was significantly (P=0.002) higher as compared with the Schnider model (Cplasma=1.0±0.4 µg/mL)., Conclusions: To perform intraoperative neurological testing, patients are required to be fully awake with plasma propofol concentrations as low as 0.8 µg/mL. Following our clinical setup, the Schnider pk/pd model estimates propofol concentrations significantly more accurate as compared with the Marsh model at this neurologically crucial time point.

Background: Anesthesia for pediatric cardiac surgery requires a high level of expert knowledge. There are currently no recommendations and standards for anesthetic management for congenital cardiac surgery in Germany., Aim: The aim of the present study was to assess the current status of structural and personnel anesthetic standards at pediatric cardiac surgery centers in Germany., Methods: All cardiac surgical centers in Germany were reviewed for an active program for congenital heart surgery. Centers with an active program were invited to respond to an online survey. The questionnaire containing 55 items in 16 categories assessed current practice in pediatric cardiac anesthesia., Results: An active program for pediatric cardiac surgery was identified at 27 centers. The response rate to the survey was 96.3%. A specialized group of anesthesiologists for pediatric cardiac anesthesia was reported from 26 centers (92.3%). The mean size of this group was 4.8 anesthesiologists per center. However, the annual case load of centers and relative annual case load per specialized anesthesiologist varied considerably between 12.5 and 250. Nonanesthesiologists performed sedation and general anesthesia for diagnostic and therapeutic interventions outside the operating theater in children with congenital heart diseases in 24 centers (77%). Although special equipment, for example, pediatric TEE, near-infrared spectroscopy, and devices for mechanical auto transfusion were available in most centers, their routine use was not always part of standard operating procedures. The proposal for mean adequate training in pediatric cardiac anesthesia as estimated by the participating centers was 10.8 months., Conclusion: The present study represents the current structural situation for anesthesia at German pediatric cardiac surgery centers., (© 2017 John Wiley & Sons Ltd.)

Purpose of Review: The current review focuses on patients with congenital heart disease (CHD) with regard to recent trends in global demographics, healthcare provision for noncardiac surgery, as well as anesthetic and perioperative care for these patients., Recent Findings: About 40 years after milestones of surgical innovation in CHD, the number of adults with CHD (ACHD) now surpasses those of children with CHD. This development leads to the fact that even patients with complex CHD managed for noncardiac surgery are not restricted to highly specialized centers. However, preoperative risk assessment for anesthesia in these patients is complex due to underlying cardiac morbidity and substantial CHD-associated noncardiac morbidity. In addition to clinical assessment and echocardiography, biomarker measurement may be a clinically useful tool to estimate severity of heart failure in CHD patients. The high negative predictive value of NT-proBNP makes it particularly valuable as a screening tool. Further, morbidity and mortality in ACHD patients are mainly caused by arrhythmias and therefore are also relevant for perioperative management. Adverse events and perioperative death in ACHD patients in cardiac and noncardiac surgery are frequently related to intraoperative anesthetic care., Summary: Medical progress in treatment of CHD has shifted morbidity and mortality of these patients largely to adulthood. Future investigations including risk stratification of ACHD patients are necessary to further improve perioperative management, especially for low-risk and high-risk noncardiac management.

Introduction: Although pediatric emergence delirium (ED) is common, preventive and therapeutic pharmacological treatment is the matter of an international controversial discussion and evidence on different options is partially vague., Objective: We therefore examined clinical routine in prevention strategies and postoperative therapy of ED with respect to clinical experience in pediatric anesthesia., Methods: A web-based survey was developed investigating routine management (prevention and treatment) of ED, facility structure, and patient population. The link was sent to all enlisted members of the German Society of Anesthesiology., Results: We analyzed 1229 questionnaires. Overall, 88% reported ED as a relevant clinical problem; however, only 5% applied assessment scores to define ED. Oral midazolam was reported as standard premedication by 84% of respondents, the second largest group was 'no premedication' (5%). The first choice prevention strategy was to perform total intravenous (propofol) anesthesia (63%). The first choice therapeutic pharmacological treatment depended on clinical experience. Therapeutic propofol was preferentially chosen by more experienced anesthesiologists (5 to >20 patients per week, n = 538), while lesser experienced colleagues (<5 patients per week, n = 676) preferentially applied opioids. Dexmedetomidine (1%) and non-pharmacological (2%) therapy were rarely stated. The highest satisfaction levels for pharmacological therapy of ED were attributed to propofol., Conclusions: Propofol is the preferred choice for pharmacological prevention and treatment of ED among German anesthesiologists. Further therapy options as well as alternatives to a midazolam-centered premedication procedure are underrepresented.

In case of apnea, arterial partial pressure of oxygen (pO2) decreases, while partial pressure of carbon dioxide (pCO2) increases. To avoid damage to hypoxia sensitive organs such as the brain, compensatory circulatory mechanisms help to maintain an adequate oxygen supply. This is mainly achieved by increased cerebral blood flow. Intermittent hypoxia is a commonly seen phenomenon in patients with obstructive sleep apnea. Acute airway obstruction can also result in hypoxia and hypercapnia. Until now, no adequate model has been established to simulate these dynamics in humans. Previous investigations focusing on human hypoxia used inhaled hypoxic gas mixtures. However, the resulting hypoxia was combined with hyperventilation and is therefore more representative of high altitude environments than of apnea. Furthermore, the transferability of previously performed animal experiments to humans is limited and the pathophysiological background of apnea induced physiological changes is poorly understood. In this study, healthy human apneic divers were utilized to mimic clinically relevant hypoxia and hypercapnia during apnea. Additionally, pulse-oximetry and Near Infrared Spectroscopy (NIRS) were used to evaluate changes in cerebral and peripheral oxygen saturation before, during, and after apnea.

Emergence Delirium in children after general anesthesia is a common and self limitating event. Although it might be seen as being harmless it can cause other serious complications and might leave both parents and other caregivers with a negative impression behind. Although the cause may still not be clear, potential predictors can be named: preschool age, the use of fast acting volatile anesthestics, higher preoperative anxiety levels and postoperative pain.A child-focused approach to reduce preoperative anxiety focusing on distraction methods rather than pharmacological sedation may be the key as well as sufficient postoperative pain control and the use of total intravenous anesthesia. Parenteal presence during induction of anaesthesia (PPIA) may be beneficial to reduce preoperative anxiety levels, but has failed to prove a better outcome regarding ED.The use of age adopted scores/scales to diagnose ED and Pain are mandatory.In the case of an ED event it is most important to protect the child from self injury and the loss of the iv-line. Postoperative pian needs to be ruled out before treating ED. Most cases can be treated by interrupting the situation and putting the child "back to sleep". Short acting drugs as Propofol have been used successfully due to its pharmacodynamics and short acting profile. Alternatively alpha-agonists or ketamin may be preferred by other authors. If potential predictors and a positive history are present, prophylactic treatment should be considered. A TIVA or the use of alpha-2-agonists have proven to be successful in reducing the risk of an ED. Midazolam may reduce preoperative anxiety but not the incidence of ED and should therefore be used carefully and is not a good choice in PACU for the treatment of ED.Parents who witnessed ED in their children should be guided and followed up. Explaining this phenomenon to parents beforehand should be part of the pre anaesthesia clinic talk and written consent.Standard protocols should be in place for treatment in the postoperative period., (© Georg Thieme Verlag Stuttgart · New York.)

Plasmacytoid dendritic cells (pDCs) are a major source of type I interferon (IFN) and are important for host defense by sensing microbial DNA via TLR9. pDCs also play a critical role in the pathogenesis of IFN-driven autoimmune diseases. Yet, this autoimmune reaction is caused by the recognition of self-DNA and has been linked to TLR9-independent pathways. Increasing evidence suggests that the cytosolic DNA receptor cyclic GMP-AMP (cGAMP) synthase (cGAS) is a critical component in the detection of pathogens and contributes to autoimmune diseases. It has been shown that binding of DNA to cGAS results in the synthesis of cGAMP and the subsequent activation of the stimulator of interferon genes (STING) adaptor to induce IFNs. Our results show that the cGAS-STING pathway is expressed and activated in human pDCs by cytosolic DNA leading to a robust type I IFN response. Direct activation of STING by cyclic dinucleotides including cGAMP also activated pDCs and knockdown of STING abolished this IFN response. These results suggest that pDCs sense cytosolic DNA and cyclic dinucleotides via the cGAS-STING pathway and that targeting this pathway could be of therapeutic interest., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Ultrasound of the inferior vena cava provides rapid and non-invasive assessment of fluid responsiveness. We hypothesized that the extensibility of the internal jugular vein (IJV) as well reflects intravascular volume state. We assessed IJV dimensions together with pulse pressure variation (PPV) as dynamic index for fluid responsiveness in mechanically ventilated patients., Methods: Of 50 patients after cardiac surgery were assessed. Ultrasound of IJV dimensions as well as collection of hemodynamic data were performed in 30° and horizontal (0°) position, and the ventilator- and position-induced IJV extensibilities (E-IJV) were calculated., Results: Mean ventilator-induced E-IJV in 30° position was 56%, and mean PPV in 30° position was 13.7%. Changing the patient's position from 30° to 0° significantly reduced ventilator-induced E-IJV as well as PPV. Pearson's correlation test revealed significant association between ventilator-induced E-IJV and fluid responsiveness deduced from PPV in 0° position (r = 0.43, P < 0.005). An E-IJV threshold >5% identified patients with significantly elevated PPV values., Conclusion: Ultrasound of the IJV and PPV as a dynamic index for fluid responsiveness can be associated under certain defined conditions. Whether or not ultrasound of the IJV can be useful to predict patient intravascular volume state should be further studied using invasive cardiac output monitoring., (© 2016 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: In case of intravascular fluid depletion, large veins react to volume expansion with dilation. Little is known about the reaction of arterial vessels. We herein report on the effect of a standardized fluid bolus on the diameter of the common carotid artery (CCA) and its association with hemodynamic parameters, assessed in 20 mechanically ventilated patients after cardiac surgery. CCA was visualized using ultrasound, and the percentage increase in diastolic diameter was calculated by measuring before and after administration of crystalloid infusion solution. Invasive arterial blood pressure and pulse pressure variation (PPV) were assessed in parallel., Results: Median diastolic CCA diameter was 6.2 (Q1-Q3: 5.4-7.1) mm, and it significantly increased to 6.7 (5.8-7.3) mm upon fluid administration [5.0 (1.9-10.5) % increase]. Mean arterial blood (MAP) pressure likewise increased from 68 (70-73) to 85 (71-100) mmHg, whereas PPV was significantly reduced from 17.6 (16.8-23.9) to 13.2 (6.7-18.1) %. There was a significant association between the change in CCA diameter and the hemodynamic response (delta-MAP: r = 0.53, delta-PPV: r = 0.56; p < 0.05). Furthermore, carotid diameter measured before volume expansion significantly correlated with the delta-PPV upon fluid administration (r = -0.5; p = 0.02)., Conclusions: Diameter of the CCA increases in response to intravascular volume expansion. Additional studies on the interplay between carotid geometry and intravascular fluid status are necessary.

Background: Critically low or high central venous pressure (CVP) values, together with systemic hypotension, can indicate hypovolemia or acute heart failure. However, measuring CVP requires the insertion of a central venous catheter, a time-consuming procedure that can be associated with severe complications., Objective: We sought to evaluate the use of ultrasonography of the internal jugular vein (IJV) to estimate low or high CVP values in patients who were on ventilation., Methods: Ultrasonography of IJV dimensions and the collection of hemodynamic data was performed in 47 patients, and the ratio between IJV diameter in the 30° and 0° position was calculated (ratio(30/0)). The predictive value of ratio(30/0) for estimating low and high CVP levels was analyzed using receiver operating characteristic curves., Results: The median IJV diameter ratio(30/0) was 0.49. CVP ranged from 1 to 13 mm Hg (median 7 mm Hg). Seventeen patients had a CVP ≤ 5 mm Hg or lower (defined as "low"), and in 11 patients, values of ≥ 10 mm Hg were measured (defined as "high"). The corresponding IJV diameter ratios increased significantly from 0.34 (in the low CVP group) to 0.9 (in the high CVP group). Receiver operating characteristic analysis revealed a good predictive value of the ratio(30/0) for the prediction of low or high CVP values, respectively. A ratio(30/0) of < 0.45 optimally indicated a low CVP, while > 0.65 was the cutoff value to detect a CVP ≥ 10 mm Hg., Conclusion: The estimation of low or high CVP values by IJV ultrasonography in different patient positions can be a helpful instrument for the rapid hemodynamic assessment of the critically ill patient., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this study we investigated the responsiveness of near-infrared spectroscopy (NIRS) recordings measuring regional cerebral tissue oxygenation (rSO2) during hypoxia in apneic divers. The goal was to mimic dynamic hypoxia as present during cardiopulmonary resuscitation, laryngospasm, airway obstruction, or the "cannot ventilate cannot intubate" situation. Ten experienced apneic divers performed maximal breath hold maneuvers under dry conditions. SpO2 was measured by Masimo™ pulse oximetry on the forefinger of the left hand. NIRS was measured by NONIN Medical's EQUANOX™ on the forehead or above the musculus quadriceps femoris. Following apnea median cerebral rSO2 and SpO2 values decreased significantly from 71 to 54 and from 100 to 65%, respectively. As soon as cerebral rSO2 and SpO2 values decreased monotonically the correlation between normalized cerebral rSO2 and SpO2 values was highly significant (Pearson correlation coefficient = 0.893). Prior to correlation analyses, the values were normalized by dividing them by the individual means of stable pre-apneic measurements. Cerebral rSO2 measured re-saturation after termination of apnea significantly earlier (10 s, SD = 3.6 s) compared to SpO2 monitoring (21 s, SD = 4.4 s) [t(9) = 7.703, p < 0.001, r(2) = 0.868]. Our data demonstrate that NIRS monitoring reliably measures dynamic changes in cerebral tissue oxygen saturation, and identifies successful re-saturation faster than SpO2. Measuring cerebral rSO2 may prove beneficial in case of respiratory emergencies and during pulseless situations where SpO2 monitoring is impossible.

Background: Anaesthesia for awake craniotomy aims for an unconscious patient at the beginning and end of surgery but a rapidly awakening and responsive patient during the awake period. Therefore, an accurate pharmacokinetic/pharmacodynamic (PK/PD) model for propofol is required to tailor depth of anaesthesia., Objective: To compare the predictive performances of the Marsh and the Schnider PK/PD models during awake craniotomy., Design: A prospective observational study., Setting: Single university hospital from February 2009 to May 2010., Patients: Twelve patients undergoing elective awake craniotomy for resection of brain tumour or epileptogenic areas., Intervention: Arterial blood samples were drawn at intervals and the propofol plasma concentration was determined., Main Outcome Measures: The prediction error, bias [median prediction error (MDPE)] and inaccuracy [median absolute prediction error (MDAPE)] of the Marsh and the Schnider models were calculated. The secondary endpoint was the prediction probability PK, by which changes in the propofol effect-site concentration (as derived from simultaneous PK/PD modelling) predicted changes in anaesthetic depth (measured by the bispectral index)., Results: The Marsh model was associated with a significantly (P = 0.05) higher inaccuracy (MDAPE 28.9 ± 12.0%) than the Schnider model (MDAPE 21.5 ± 7.7%) and tended to reach a higher bias (MDPE Marsh -11.7 ± 14.3%, MDPE Schnider -5.4 ± 20.7%, P = 0.09). MDAPE was outside of accepted limits in six (Marsh model) and two (Schnider model) of 12 patients. The prediction probability was comparable between the Marsh (PK 0.798 ± 0.056) and the Schnider model (PK 0.787 ± 0.055), but after adjusting the models to each individual patient, the Schnider model achieved significantly higher prediction probabilities (PK 0.807 ± 0.056, P = 0.05)., Conclusion: When using the 'asleep-awake-asleep' anaesthetic technique during awake craniotomy, we advocate using the PK/PD model proposed by Schnider. Due to considerable interindividual variation, additional monitoring of anaesthetic depth is recommended., Trial Registration: ClinicalTrials.gov identifier: NCT 01128465.

Background: The origin of emergence agitation in children remains unclear; however, an association between surgical procedure, patient age and anesthetic regimen and the incidence of postoperative agitation has been described in the literature., Aim: The aim of this survey performed between February and April 2014 was to collect data from the daily clinical practice by experienced pediatric anesthesiologists regarding documentation, premedication, anesthesia regimen and postoperative treatment with respect to children with emergence agitation., Material and Methods: An online questionnaire with 33 items was developed and sent to all 525 members of the scientific committee of pediatric anesthesia (WAKKA) of the German Society of Anesthesiology and Intensive Care (DGAI). Members were asked to respond within a time period of 1 month but no reminders were sent out via email or telephone., Results: A total of 156 members participated in the survey and of these 143 questionnaires were fully completed and included in the final evaluation (27 %). Of the participants 77 % had more than 6 years professional experience in the field of pediatric anesthesia and for 87 % emergence agitation remains a relevant clinical problem. The estimated incidence of emergence agitation was given as 1-10 % and as high as 11-20 % by 56% and 20 % of the participants, respectively. The incidence of postoperative agitation is documented by only 11 % of the participants with a validated score, such as the pediatric anesthesia emergence delirium (PEAD) scale and 89 % of the participants use midazolam for premedication. As a preemptive intervention total intravenous anesthesia is performed by 56 % whereas clonidine is used as first line prevention by 30 %. Postoperative pharmacological treatment is performed by a bolus administration of propofol (56 %) and clonidine (26 %). Postoperative parental presence was considered beneficial by 82 %., Conclusion: Emergence agitation is still seen as a relevant clinical problem by experienced pediatric anesthesiologists. Propofol is first choice when it comes to pharmacological prevention and treatment of emergence agitation. Postoperative parental presence was considered beneficial by the majority of anesthesiologists.

Background: Postoperative delirium (POD) occurs frequently after cardiac surgery and is associated with increased morbidity and mortality. We analysed whether perioperative bilateral BIS monitoring may detect abnormalities before the onset of POD in cardiac surgery patients., Methods: In a prospective observational study, 81 patients undergoing cardiac surgery were included. Bilateral Bispectral Index (BIS)-monitoring was applied during the pre-, intra- and postoperative period, and BIS, EEG Asymmetry (ASYM), and Burst Suppression Ratio (BSR) were recorded. POD was diagnosed according to the Confusion Assessment Method for the Intensive Care Unit, and patients were divided into a delirium and non-delirium group., Results: POD was detected in 26 patients (32%). A trend towards a lower ASYM was observed in the delirium group as compared to the non-delirium group on the preoperative day (ASYM = 48.2 ± 3.6% versus 50.0 ± 4.7%, mean ± sd, p = 0.087) as well as before induction of anaesthesia, with oral midazolam anxiolysis (median ASYM = 49.5%, IQR [47.4;51.5] versus 50.6%, IQR [49.1;54.2], p = 0.081). Delirious patients remained significantly (p = 0.018) longer in a burst suppression state intraoperatively (107 minutes, IQR [47;170] versus 44 minutes, IQR [11;120]) than non-delirious patients. Receiver operating analysis revealed burst suppression duration (area under the curve = 0.73, p = 0.001) and BSR (AUC = 0.68, p = 0.009) as predictors of POD., Conclusions: Intraoperative assessment of BSR may identify patients at risk of POD and should be investigated in further studies. So far it remains unknown whether there is a causal relationship or rather an association between intraoperative burst suppression and the development of POD., Trial Registration: clinicaltrials.gov NCT01048775.

Background: Electroconvulsive therapy (ECT) is a highly effective and established treatment for depression. Magnetic seizure therapy (MST) has recently been developed and seems equally effective while associated with fewer side-effects. Both require general anaesthesia, which could be quantified using the bispectral index (BIS). We compared ECT and MST with respect to recovery times, left-sided BIS, and left-right differences in BIS., Methods: In this prospective, observational study, we enrolled 10 successive patients receiving ECT and 10 patients undergoing MST. Anaesthesia was performed with propofol and monitored with a bilateral BIS sensor. The seizure was elicited when the BIS was within a range from 50 to 60. The time to eye opening was measured and bilateral BIS were recorded for 10 min after seizure induction., Results: A comparable anaesthetic depth was observed in the ECT and MST groups at baseline [mean (standard deviation, sd) BIS values of 94.1 (4.1) and 95.5 (3.0), respectively] and before seizure induction [mean (sd) BIS values of 52.3 (9.6) and 55.2 (10.3), respectively]. Post-ictally, MST patients opened their eyes significantly earlier than ECT patients [3.0 (1.0) vs 6.7 (1.3) min, P<0.001]. They showed a significantly higher BIS at 2 min after seizure induction [69.2 (10.1) vs 50.9 (15.9), P=0.003], and this difference was still present at 10 min after seizure induction [BIS 81.5 (6.5) vs 68.0 (16.4), P<0.001]. Significant differences between the left and right BIS were observed in neither the ECT nor the MST group., Conclusions: At a comparable anaesthetic depth, MST is superior to ECT in terms of post-ictal recovery, which is correctly reflected by higher post-ictal BIS values. Unilateral BIS monitoring is sufficient to monitor anaesthetic depth in ECT and MST patients. TRIAL REGISTRY NUMBER: NCT 01318018.

To easily measure the depth of anaesthesia during routine surgical procedures has always been a goal in anaesthesiology. For decades, scientists have been developing indices to describe and evaluate the depth of anaesthesia. Historically, mean alveolar gas concentration (MAC) values for volatile anaesthetics have been used to target a predefined level of anaesthesia. MAC values were however not established to differentiate between the hypnotic and analgesic components of anaesthesia. Indices were therefore developed that measure the effect of hypnotics predominantly on the brain (in contrast to an effect on the spinal cord) with the vision to be able to measure the transition from consciousness to unconsciousness. Although monitors measuring the depth of anaesthesia are still not capable of measuring the transition from consciousness to unconsciousness, brain monitoring has proved to help clinicians control the depth of anaesthesia. Clinical trials have shown that the use of brain-monitoring devices can lead to a reduction of intraoperative drug consumption, reduced incidence of postoperative nausea and vomiting, facilitate recovery from anaesthesia compared to routine care and can also lead to a reduction of intraoperative awareness. However a study demonstrating both a reduced intraoperative drug consumption and at the same time a reduction of intraoperative awareness due to the use of brain-monitoring devices has not been published yet., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Background: Recently the Composite Variability Index (CVI) was developed to quantify nociception. This index is derived from the standard deviations (s) of the Bispectral Index (sBIS) and the electromyogram (sEMG). The primary aim of our study was to compare CVI before and after a noxious stimulus. As secondary end points, we investigated the influence of remifentanil on the CVI and tested the ability of the CVI to indicate patient movement after a noxious stimulus under changing remifentanil concentrations. Furthermore, we measured the increase in CVI after a noxious stimulus in comparison to other clinical variables (BIS, sBIS, sEMG, heart rate [HR], and systolic blood pressure [BP(sys)])., Methods: Twenty-four patients without a history of cardiac disease were investigated. Anesthesia was induced with propofol administered by target-controlled infusion. A standardized noxious electrical stimulus was applied (50 Hz, 70 mA, 30 seconds) to the ulnar nerve at increasing or decreasing remifentanil effect-compartment concentrations (Ce(remi)). Changes in baseline and poststimulus CVI, BIS, sBIS, sEMG, HR, and BP(sys) were investigated. Parameters' ability to indicate movement after a noxious stimulus was evaluated with the prediction probability (P(K))., Results: All investigated parameters (except BP(sys)) increased significantly after a noxious stimulus at 0, 1, 2, or 3 ng·mL(-1) Ce(remi). The association between poststimulus maximal parameters and movement were P(K) = 0.81 for HR, P(K) = 0.78 for sEMG, and P(K) = 0.72 for CVI (pairwise difference to CVI statistically nonsignificant). The association between ΔsEMG or ΔCVI (poststimulus value minus baseline value) and movement was significantly higher (P(K) = 0.76 and 0.75, respectively) compared with ΔHR (P(K) = 0.53) (P = 0.008 and P = 0.01, respectively). Receiver operating characteristic analysis revealed a threshold value for movement for ΔCVI of >0.39 (sensitivity of 0.71, specificity of 0.74) and for ΔsEMG of >0.31 (sensitivity of 0.68, specificity of 0.78)., Conclusion: In paralyzed patients, ΔsEMG and ΔCVI might help identify inadequately low levels of analgesia with an acceptable sensitivity and specificity. The impact of profound neuromuscular block on the CVI should be investigated in further studies.

Background: The patient state index (PSI) and the bispectral index (BIS) quantify anaesthetic depth based on the EEG using different algorithms. We compared both indices with regard to the prediction of the depth of propofol anaesthesia., Methods: In 17 patients, propofol was infused until burst suppression occurred and stopped thereafter until BIS recovered to values above 60. This was repeated; afterwards, patients were intubated, for subsequent surgery. Without surgical stimulus, PSI and BIS were measured simultaneously and compared with the estimated effect-site concentrations of propofol. These were derived from simultaneous pharmacokinetic and -dynamic modelling in an individual two-stage and a population-based NONMEM approach., Results: A close sigmoid relationship was observed between the propofol effect-site concentration and both PSI [coefficient of determination rho(2)=0.91 (sd 0.05)] and BIS [rho(2)=0.92 (0.03)], which was significantly steeper for PSI [gamma=2.2 (0.6)] than for BIS [gamma=1.8 (0.4)], and reached significantly lower values for PSI [E(max)=0.3 (1.1)] than for BIS [E(max)=5.3 (6.7)] at maximal propofol concentrations. A significantly smaller k(e0) was obtained for PSI [0.09 (0.03) min(-1)] compared with BIS [0.10 (0.02) min(-1)]. PSI and BIS correlated significantly with each other (rho(2)=0.866) and predicted propofol effect-site concentration with a comparable probability [P(K)=0.87 (0.05) and 0.86 (0.05), respectively]. NONMEM revealed E(0)=89.3 and 92.3, E(max)=1.9 and 8.6, C(e50)=1.38 and 1.92 microg ml(-1), gamma=1.6 and 1.48, and k(e0)=0.103 and 0.131 min(-1) as typical values for PSI and BIS, respectively., Conclusions: The PSI and the BIS monitors performed equally well in predicting depth of propofol anaesthesia. However, PSI was lower than BIS by approximately 10-15 points at high propofol concentrations.

Aim: This survey assessed procedures performed by general dentists in German university hospitals treating patients with chronic orofacial pain (COP)., Methods: A standardized questionnaire was sent to dentists at all 42 German universities. Doctors were asked to describe demographics, diagnoses, etiologies, diagnostic, and treatment procedures for their patients seen over a 3-month period., Results: A total of 34,242 patients from 19 responding university hospitals were enrolled. COP of greater than 6 months duration was identified in 1,767 patients (5.2%), of whom 64% were female, 76% were between 20 and 59 years old, 66.3% frequently changed doctors, and 29.5% demonstrated psychological comorbidities. The most common causes of COP were temporomandibular disorders, atypical odontalgia, and atypical facial pain accounting for 83.4% of the sample, with purported etiologies of surgery or trauma (52.4%), musculoskeletal disorders (24.2%), prosthetics (11.4%), or psychosomatic causes (11.7%). A secondary pain syndrome was found in 25% of patients. Before admission to the universities, 59.4% of patients reported inadequate pain control. Following admission, the number of patients receiving specialized therapies significantly increased from 40.6% to 88.2% (chi(2) test; P < 0.001), and improved pain was reported in 71.4% of patients. Multimodal therapy included treatment of malocclusion (47.1%), surgery (37.7%), analgesics (27.5%), and physiotherapy (22%). Specialized pain assessment (26.5%) or visual analog scales (16.9%) were applied irregularly and pain therapists were rarely consulted (8.9%). Despite the high psychological comorbidity (29.5%), psychological treatments were obtained for only 11%., Conclusions: The prevalence of COP is 5% in German University dental practices, where current guidelines of COP treatment are followed incompletely, and patients with psychological disorders are usually not treated. Interdisciplinary practice principles should be encouraged.

Background: The k(e)(0) value is the first order rate constant determining the equilibration of drugs between plasma or end-tidal concentration and effect-site (e.g., brain) concentration. Parametric and semiparametric approaches have been used for estimating individual k(e)(0) values and describing the drug-response curve. In this study, we introduce a new semiparametric approach calculating k(e)(0) values for isoflurane, sevoflurane, and desflurane by maximizing the prediction probability P(K)., Methods: Data from 45 patients scheduled for a radical prostatectomy were analyzed. After lumbar epidural catheterization, patients received remifentanil and propofol solely for induction of anesthesia. Thereafter, epidural analgesia was initiated, and isoflurane, sevoflurane, or desflurane (15 patients each) was added to maintain unconsciousness. At least 45 min later, end-tidal concentrations were varied between 0.5 and 2 minimum alveolar anesthetic concentration. We estimated an individual k(e)(0) value for each patient by optimizing the prediction probability P(K) (P(K)-based k(e)(0)) or by minimizing the area within the hysteresis loop (area-based k(e)(0)). Data are mean +/- sd., Results: Both semiparametric approaches led to comparable k(e)(0) values with 0.18 +/- 0.06 min(-1) (P(K) based) and 0.15 +/- 0.04 min(-1) (area based) for isoflurane and 0.17 +/- 0.08 min(-1) (P(K) based) and 0.16 +/- 0.11 min(-1) (area based) for sevoflurane. k(e)(0) values for desflurane (P(K) based: 0.30 +/- 0.17min(-1); area based: 0.32 +/- 0.25 min(-1)) were significantly higher than for isoflurane and sevoflurane., Conclusion: Maximizing the prediction probability P(K) for estimating k(e)(0) seems to be a promising method that researchers could use on an exploratory basis.

Background: Automated indices derived from mid-latency auditory evoked potentials (MLAEP) have been proposed for monitoring the state of anaesthesia. The A-Line ARX index (AAI) has been implemented in the A-Line monitor (Danmeter, V1.4). Several studies have reported variable and, in awake patients, sometimes surprisingly low AAI values. The purpose of this study was to reproduce these findings under steady-state conditions and to investigate their causes., Methods: Ten awake unmedicated volunteers were studied under steady-state conditions. For each subject, the raw EEG and the AAI were recorded with an A-Line monitor (V1.4) during three separate sessions of 45.0 (1.6) min duration each. MATLAB (Mathworks) routines were used to derive MLAEP responses from EEG data and to calculate maximal MLAEP amplitudes., Results: The AAI values ranged from 15 to 99, while 11.4% fell below levels which, according to the manufacturer, indicate an anaesthetic depth suitable for surgery. Inter-individual and intra-individual variation was observed despite stable recording conditions. The amplitudes of the MLAEP varied from 0.8 to 42.0 microV. The MLAEP amplitude exceeded 2 microV in 75.3% of readings. The Spearman's rank correlation coefficient between the MLAEP amplitude and the AAI value was r=0.89 (P<0.0001)., Conclusions: The version of the A-Line monitor used in this study does not exclude contaminated MLAEP signals. Previous publications involving this version of the A-Line monitor (as opposed to the newer A-Line/2 monitor series) should be reassessed in the light of these findings. Before exclusively MLAEP-based monitors can be evaluated as suitable monitors of depth of anaesthesia, it is essential to ensure that inbuilt validity tests eliminate contaminated MLAEP signals.

Background: Several studies have shown a reduction in anaesthetic drug consumption with Bispectral Index (BIS) titration compared with standard clinical practice. However, the amount of reduction varied widely between 1% and 40%. We investigated the correlation between reduction in anaesthetic drug consumption and mean titrated BIS values., Methods: An analysis upon randomized controlled trials cited until January 2006 in MEDLINE and other databases investigating the potential reduction in anaesthetic (hypnotic) drug consumption with BIS titration was performed. Investigations with a marked difference (> 15%) in opioid drug consumption between the BIS group and the standard practice group were excluded. Correlations between amount of reduction in hypnotic drug use and the mean titrated BIS value were analysed with linear regression., Results: Fourteen manuscripts covering 2582 patients were included into the analysis. The mean BIS value in the standard clinical practice group averaged over all studies was 43.6 +/- 3.2 and the mean BIS value in the BIS-titrated group was 49.9 +/- 5.4. The amount of reduction in hypnotic drug use correlated significantly with the mean BIS values in the BIS-titrated groups (r =0.68) and with the differences between the mean BIS value in the BIS-titrated group and the mean BIS value in the standard clinical practice group (r = 0.70). Every point of BIS difference between the two groups resulted in a reduced hypnotic drug use of approximately 2%., Conclusion: Despite differences in the study designs and in the drugs used, a linear correlation between the mean titrated BIS value and the hypnotic drug saving potential was found.

Recently, Datex-Ohmeda introduced the Entropy Moduletrade mark for measuring depth of anesthesia. Based on the Shannon entropy of the electroencephalogram, state entropy (SE) and response entropy (RE) are computed. We investigated the dose-response relationship of SE and RE during propofol anesthesia in comparison with the Bispectral Indextrade mark (BIS). Twenty patients were studied without surgical stimulus. Anesthesia was induced by a constant propofol infusion of 2000 mg/h (451 +/- 77 microg x min(-1) x kg(-1)) via a large forearm vein. Propofol was infused until substantial burst suppression occurred (more than 50%) or mean arterial blood pressure decreased to <60 mm Hg. Hereafter, infusions were stopped until recovery of BIS values up to 60 was reached. Subsequently, the constant propofol infusion of 2000 mg/h was restarted to increase depth of anesthesia and again decreased (infusion was stopped) within the BIS value range of 40-60. The coefficient of determination (R2) and the prediction probability (P(K)) were calculated to evaluate the performance of SE, RE, and BIS to predict changing propofol effect-site concentrations. R2 values for SE, RE, and BIS of 0.88 +/- 0.08, 0.89 +/- 0.07, and 0.92 +/- 0.06, respectively, were similar. The calculated P(K) values, however, revealed a significant difference between SE and RE compared with BIS, with P(K) = 0.77 +/- 0.09, 0.76 +/- 0.10, and 0.84 +/- 0.06, respectively. BIS seems to show slight advantages in predicting propofol effect-site concentrations compared with SE and RE, as measured by P(K) but not as measured by R2.

Background: Recently, entropy algorithms have been proposed as electroencephalographic measures of anesthetic drug effects. Datex-Ohmeda (Helsinki, Finland) introduced the Entropy Module, a new electroencephalographic monitor designed for measuring depth of anesthesia. The monitor calculates a state entropy (SE) computed over the frequency range of 0.8-32 Hz and a response entropy (RE) computed over the frequency range of 0.8-47 Hz. The authors investigated the dose-response relation of SE and RE during sevoflurane anesthesia in comparison with the Bispectral Index (BIS)., Methods: Sixteen patients were studied without surgical stimulus. Anesthesia was induced by sevoflurane inhalation with a tight-fitting facemask. Sevoflurane concentrations were increased and subsequently decreased and increased two to four times until the measurement was stopped and patients were intubated for surgery. The performances of SE, RE, and BIS to predict the estimated sevoflurane effect site concentration, obtained by simultaneous pharmacokinetic and pharmacodynamic modeling, were compared by calculating the correlation coefficients and the prediction probability., Results: State entropy, RE, and BIS values decreased continuously over the observed concentration range of sevoflurane. Correlation coefficients were slightly but not significantly better for entropy parameters (0.87 +/- 0.09 and 0.86 +/- 0.10 for SE and RE, respectively) than for BIS (0.85 +/- 0.12). Calculating the prediction probability confirmed these results with a prediction probability of 0.84 +/- 0.05 and 0.82 +/- 0.06 for SE and RE, respectively, and 0.80 +/- 0.06 for BIS., Conclusion: State entropy and RE seem to be useful electroencephalographic measures of sevoflurane drug effect.

Objective: Artefact detection is an essential feature of automatic EEG monitoring systems used in anaesthesia. Clinical experience indicates that Narcotrend monitoring (MonitorTechnik, Bad Bramstedt, Germany, version 4.0) excludes more EEG epochs because of artefacts than bispectral index monitoring (BIS, Aspect Medical Systems, Newton, MA, version XP). Whether this increased exclusion of epochs is justified has not been investigated yet., Methods: Eighteen adult patients undergoing radical prostatectomy were investigated. Induction of anaesthesia was performed with a fentanyl bolus and a propofol infusion. Additionally, following intubation patients received 15 ml bupivacaine 0.5% epidurally. After a waiting period of 45 min depth of anaesthesia was varied two times by increasing and decreasing propofol concentrations. Narcotrend index, BIS values and calculated propofol effect site concentrations were automatically recorded at intervals of 5 s. We tested the hypothesis whether exclusion of artefacts detected by the Narcotrend monitor would possibly improve the prediction probability of the BIS monitor, justifying the necessity of artefact suppression., Results: Simulated propofol effect site concentrations ranged from 2 microg/ml to 6 microg/ml. The Narcotrend monitor excluded a significantly higher percentage of epochs because of artefact detection (12.6 + 1.0%) than the BIS monitor (0.4 +/- 0.1%). The performance of BIS as an indicator of predicted propofol effect site concentrations did not differ when including (P(K) = 0.86 +/- 0.05) or excluding (P(K) = 0.85 +/- 0.04) the data pairs where Narcotrend monitor but not BIS monitor indicated an artefact. Artefacts were evenly distributed over the investigated range ofpropofol effect site concentrations., Conclusion: Exclusion of data pairs that were detected as artefacts by Narcotrend but not by BIS did not change the performance of bispectral index as an indicator of propofol effect site concentration.

Status epilepticus (S.E.) is known to lead to a large number of changes in the expression of voltage-dependent ion channels and neurotransmitter receptors. In the present study, we examined whether an episode of S.E. induced by pilocarpine in vivo alters functional properties and expression of voltage-gated Na(+) channels in dentate granule cells (DGCs) of the rat hippocampus. Using patch-clamp recordings in isolated DGCs, we show that the voltage-dependent inactivation curve is significantly shifted toward depolarizing potentials following S.E. (half-maximal inactivation at -43.2+/-0.6 mV) when compared with control rats (-48.2+/-0.8 mV, P<0.0001). The voltage-dependent activation curve is significantly shifted to more negative potentials following S.E., with half-maximal activation at -28.6+/-0.8 mV compared with -25.8+/-0.9 mV in control animals (P<0.05). The changes in voltage dependence resulted in an augmented window current due to increased overlap between the activation and inactivation curve. In contrast to Na(+) channel voltage-dependence, S.E. caused no changes in the kinetics of fast or slow recovery from inactivation. The functional changes were accompanied by altered expression of Na(+) channel subunits measured by real-time reverse transcription-polymerase chain reaction in dentate gyrus microslices. We investigated expression of the pore-forming alpha subunits Na(v)1.1-Na(v)1.3 and Na(v)1.5-Na(v)1.6, in addition to the accessory subunits beta(1) and beta(2). The Na(v)1.2 and Na(v)1.6 subunit as well as the beta(1) subunit were persistently down-regulated up to 30 days following S.E. The beta(2) subunit was transiently down-regulated on the first and third day following S.E. These results indicate that differential changes in Na(+) channel subunit expression occur in concert with functional changes. Because coexpression of beta subunits is known to robustly shift the voltage dependence of inactivation in a hyperpolarizing direction, we speculate that a down-regulation of beta-subunit expression may contribute to the depolarizing shift in the inactivation curve following S.E.

1. Fundamental to the understanding of CNS function is the question of how individual neurons integrate multiple synaptic inputs into an output consisting of a sequence of action potentials carrying information coded as spike frequency. The availability for activation of neuronal Na(+) channels is critical for this process and is regulated both by fast and slow inactivation processes. Here, we have investigated slow inactivation processes in detail in hippocampal neurons. 2. Slow inactivation was induced by prolonged (10-300 s) step depolarisations to -10 mV at room temperature. In isolated hippocampal dentate granule cells (DGCs), recovery from this inactivation was biexponential, with time constants for the two phases of slow inactivation tau(slow,1) and tau(slow,2) ranging from 1 to 10 s and 20 to 50 s, respectively. Both (slow,1) and tau(slow,2) were related to the duration of prior depolarisation by a power law function of the form tau(t) = a (t/a)b, where t is the duration of the depolarisation, a is a constant kinetic setpoint and b is a scaling power. This analysis yielded values of a = 0.034 s and b = 0.62 for tau(slow,1) and a = 24 s and b = 0.30 for tau(slow,2) in the rat. 3. When a train of action potential-like depolarisations of different frequencies (50, 100, 200 Hz) was used to induce inactivation, a similar relationship was found between the frequency of depolarisation and both tau(slow,1) and tau(slow,2) (a = 0.58 s, b = 0.39 for tau(slow,1) and a = 3.77 s and b = 0.42 for tau(slow,2)). 4. Using nucleated patches from rat hippocampal slices, we have addressed possible cell specific differences in slow inactivation. In fast-spiking basket cells a similar scaling relationship can be found (a = 3.54 s and b = 0.39) as in nucleated patches from DGCs (a = 2.3 s and b = 0.48) and non-fast-spiking hilar neurons (a = 2.57 s and b = 0.49). 5. Likewise, comparison of human and rat granule cells showed that properties of ultra-slow recovery from inactivation are conserved across species. In both species ultra-slow recovery was biexponential with both tau(slow,1) and tau(slow,2) being related to the duration of depolarisation t, with a = 0.63 s and b = 0.44 for tau(slow,1) and a = 25 s and b = 0.37 for tau(slow,2) for the human subject. 6. In summary, we describe in detail how the biophysical properties of Na(+) channels result in a complex interrelationship between availability of sodium channels and membrane potential or action potential frequency that may contribute to temporal integration on a time scale of seconds to minutes in different types of hippocampal neurons.