Fractal Analysis of the Cerebrovascular System Pathophysiology.

The cerebrovascular system is characterized by parameters such as arterial blood pressure (ABP), cerebral perfusion pressure (CPP), and cerebral blood flow velocity (CBFV). These are regulated by interconnected feedback loops resulting in a fluctuating and complex time course. They exhibit fractal characteristics such as (statistical) self-similarity and scale invariance which could be quantified by fractal measures. These include the coefficient of variation, the Hurst coefficient H, or the spectral exponent α in the time domain, as well as the spectral index ß in the frequency domain. Prior to quantification, the time series has to be classified as either stationary or nonstationary, which determines the appropriate fractal analysis and measure for a given signal class. CBFV was characterized as a nonstationary (fractal Brownian motion) signal with spectral index ß between 2.0 and 2.3. In the high-frequency range (>0.15 Hz), CBFV variability is mainly determined by the periodic ABP variability induced by heartbeat and respiration. However, most of the spectral power of CBFV is contained in the low-frequency range (<0.15 Hz), where cerebral autoregulation acts as a low-pass filter and where the fractal properties are found. Cerebral vasospasm, which is a complication of subarachnoid hemorrhage (SAH), is associated with an increase in ß denoting a less complex time course. A reduced fractal dimension of the retinal microvasculature has been observed in neurodegenerative disease and in stroke. According to the decomplexification theory of illness, such a diminished complexity could be explained by a restriction or even dropout of feedback loops caused by disease.

Post-COVID-19 pandemic organ donation activities in Germany: a multicenter retrospective analysis.

Introduction: The COVID-19 pandemic had a negative impact on the number of solid organ transplantations. After a global decline of 16% in 2020, their numbers subsequently returned to pre-pandemic levels. In contrast, numbers in Germany remained almost constant in 2020 and 2021 but fell by 6.9% in 2022. The reasons for this divergent development are unknown. Methods: The number of deceased with a severe brain damage, potential and utilized donors after braindeath and the intensive care unit treatment capacity were retrospectively compared for the years 2022 and 2021 at five university hospitals in North Rhine-Westphalia, Germany. Reasons for a donation not utilized were reviewed. To enable a comparison of the results with the whole of Germany and the pre-pandemic period, numbers of potential and utilized donors were extracted from official organ donation activity reports of all harvesting hospitals in Germany for the years 2019-2022. Results: The numbers of deceased with a severe brain damage (-10%), potential (-9%), and utilized donors after braindeath (-44%), and intensive care unit treatment capacities (-7.2%) were significantly lower in 2022 than 2021. A COVID-19 infection was a rarer (-79%), but donor instability (+44%) a more frequent reason against donation in 2022, whereas preserved brain stem reflexes remained the most frequent reason in both years (54%). Overall numbers of potential and utilized donations in Germany were lower in 2022 than in the pre-pandemic period, but this was mainly due to lower numbers in hospitals of lower care. The number of potential donors in all university hospitals were higher in 2022 but utilized donations still lower than in 2019. Conclusion: The decrease in potential and utilized donations was a result of reduced intensive care unit treatment capacities and a lower conversion rate at the five university hospitals. A COVID-19 infection did not play a role in 2022. These results indicate that ICU treatment capacities must be restored to increase donations. The lower number of potential donors and the even lower conversion rate in 2022 throughout Germany show that restructuring the organ procurement process in Germany needs to be discussed to increase the number of donations.

Effect of Extracerebral Contamination on Near-infrared Spectroscopy as Revealed during Organ Donation: A Prospective Observational Study in Brain-dead Organ Donors.

BACKGROUND: Near-infrared spectroscopy (NIRS) has been utilized widely in anesthesia and intensive care to monitor regional cerebral oxygen saturation (rScO2). A normal oxygenation of extracerebral tissues may overlay and thereby mask cerebral desaturations, a phenomenon known as extracerebral contamination. The authors investigated the effect of a cessation of extracerebral tissue perfusion on rScO2 in patients with anoxic brains. METHODS: In a single-center, prospective, observational study, brain-dead adults undergoing organ donation were investigated. rScO2 was measured bifrontally using the INVOS 5100C/7100 as well as the ForeSight Elite system. To achieve an efficient conservation of organs and to prevent a redistribution of the perfusion fluid to other tissues, the aorta was clamped before organ perfusion. rScO2 was monitored until at least 40 min after aortic clamping. The primary outcome was the amount of extracerebral contamination as quantified by the absolute decrease in rScO2 after aortic clamping. Secondary outcomes were the absolute rScO2 values obtained before and after clamping. RESULTS: Twelve organ donors were included. Aortic clamping resulted in a significantly (P < 0.001) greater absolute decrease in rScO2 when comparing the INVOS (43.0 ± 9.5%) to the ForeSight (27.8 ± 7.1%) monitor. Before aortic clamping, near-normal rScO2 values were obtained by the INVOS (63.8 ± 6.2%) and the ForeSight monitor (67.7 ± 6.5%). The rScO2 significantly (P < 0.001) dropped to 20.8 ± 7.8% (INVOS) and 39.9 ± 8.1% (ForeSight) 30 min after clamping, i.e., a condition of a desaturation of both extracerebral and cerebral tissues. CONCLUSIONS: The abrupt end of extracerebral contamination, caused by aortic clamping, affected both NIRS monitors to a considerable extent. Both the INVOS and the ForeSight monitor were unable to detect severe cerebral hypoxia or anoxia under conditions of normal extracerebral oxygenation. While both NIRS monitors may guide measures to optimize arterial oxygen supply to the head, they should not be used with the intention to detect isolated cerebral desaturations.

Preoperative Midazolam and Patient-Centered Outcomes of Older Patients: The I-PROMOTE Randomized Clinical Trial.

Importance: The effect of oral midazolam premedication on patient satisfaction in older patients undergoing surgery is unclear, despite its widespread use. Objective: To determine the differences in global perioperative satisfaction in patients with preoperative administration of oral midazolam compared with placebo. Design, Setting, and Participants: This double-blind, parallel-group, placebo-controlled randomized clinical trial was conducted in 9 German hospitals between October 2017 and May 2019 (last follow-up, June 24, 2019). Eligible patients aged 65 to 80 years who were scheduled for elective inpatient surgery for at least 30 minutes under general anesthesia and with planned extubation were enrolled. Data were analyzed from November 2019 to December 2020. Interventions: Patients were randomized to receive oral midazolam, 3.75 mg (n = 309), or placebo (n = 307) 30 to 45 minutes prior to anesthesia induction. Main Outcomes and Measures: The primary outcome was global patient satisfaction evaluated using the self-reported Evaluation du Vécu de l'Anesthésie Generale (EVAN-G) questionnaire on the first postoperative day. Key secondary outcomes included sensitivity and subgroup analyses of the primary outcome, perioperative patient vital data, adverse events, serious complications, and cognitive and functional recovery up to 30 days postoperatively. Results: Among 616 randomized patients, 607 were included in the primary analysis. Of these, 377 (62.1%) were male, and the mean (SD) age was 71.9 (4.4) years. The mean (SD) global index of patient satisfaction did not differ between the midazolam and placebo groups (69.5 [10.7] vs 69.6 [10.8], respectively; mean difference, -0.2; 95% CI, -1.9 to 1.6; P = .85). Sensitivity (per-protocol population, multiple imputation) and subgroup analyses (anxiety, frailty, sex, and previous surgical experience) did not alter the primary results. Secondary outcomes did not differ, except for a higher proportion of patients with hypertension (systolic blood pressure ≥160 mm Hg) at anesthesia induction in the placebo group. Conclusion and Relevance: A single low dose of oral midazolam premedication did not alter the global perioperative patient satisfaction of older patients undergoing surgery or that of patients with anxiety. These results may be affected by the low dose of oral midazolam. Further trials-including a wider population with commonplace low-dose intravenous midazolam and plasma level measurements-are needed. Trial Registration: ClinicalTrials.gov Identifier: NCT03052660.

Influence of Intraoperative Nociception during Hip or Knee Arthroplasty with Supplementary Regional Anaesthesia on Postoperative Pain and Opioid Consumption.

Background and Objectives: Early postoperative mobilization is central for postoperative outcomes after lower extremity joint replacement surgery. By providing adequate pain control, regional anaesthesia plays an important role for postoperative mobilization. It was the objective of this study to investigate the use of the nociception level index (NOL) to determine the effect of regional anaesthesia in hip or knee arthroplasty patients undergoing general anaesthesia with additional peripheral nerve block. Materials and Methods: Patients received general anaesthesia, and continuous NOL monitoring was established before anaesthesia induction. Depending on the type of surgery, regional anaesthesia was performed with a Fascia Iliaca Block or an Adductor Canal Block. Results: For the final analysis, 35 patients remained, 18 with hip and 17 with knee arthroplasty. We found no significant difference in postoperative pain between hip or knee arthroplasty groups. NOL increase at the time of skin incision was the only parameter associated with postoperative pain measured using a numerical rating scale (NRS > 3) after 24 h in movement (-12.3 vs. +119%, p = 0.005). There was no association with intraoperative NOL values and postoperative opioid consumption, nor was there an association between secondary parameters (bispectral index, heart rate) and postoperative pain levels. Conclusions: Intraoperative NOL changes may indicate regional anaesthesia effectiveness and could be associated with postoperative pain levels. This remains to be confirmed in a larger study.

Cerebral blood flow autoregulation assessment by correlation analysis between mean arterial blood pressure and transcranial doppler sonography or near infrared spectroscopy is different: A pilot study.

PURPOSE: Recently, cerebral autoregulation indices based on moving correlation indices between mean arterial pressure (MAP) and cerebral oximetry (NIRS, ORx) or transcranial Doppler (TCD)-derived middle cerebral artery flow velocity (Mx) have been introduced to clinical practice. In a pilot study, we aimed to evaluate the validity of these indices using incremental lower body negative pressure (LBNP) until presyncope representing beginning cerebral hypoperfusion as well as lower body positive pressure (LBPP) with added mild hypoxia to induce cerebral hyperperfusion in healthy subjects. METHODS: Five male subjects received continuous hemodynamic, TCD and NIRS monitoring. Decreasing levels of LBNP were applied in 5-minute steps until subjects reached presyncope. Increasing levels of LBPP were applied stepwise up to 20 or 25 mmHg. Normobaric hypoxia was added until an oxygen saturation of 84% was reached. This was continued for 10 minutes. ORx and Mx indices were calculated using previously described methods. RESULTS: Both Indices showed an increase > 0.3 indicating impaired cerebral autoregulation during presyncope. However, there was no significant difference in Mx at presyncope compared to baseline (p = 0.168). Mean arterial pressure and cardiac output decreased only in presyncope, while stroke volume was decreased at the last pressure level. Neither Mx nor ORx showed significant changes during LBPP or hypoxia. Agreement between Mx and ORx was poor during the LBNP and LBPP experiments (R2 = 0.001, p = 0.3339). CONCLUSION: Mx and ORx represent impaired cerebral autoregulation, but in Mx this may not be distinguished sufficiently from baseline. LBPP and hypoxia are insufficient to reach the upper limit of cerebral autoregulation as indicated by Mx and ORx.

How Large is the Potential of Brain Dead Donors and what Prevents Utilization? A Multicenter Retrospective Analysis at Seven University Hospitals in North Rhine-Westphalia.

Organ donation after brain death is constantly lower in Germany compared to other countries. Instead, representative surveys show a positive attitude towards donation. Why this does not translate into more donations remains questionable. We retrospectively analyzed all potential brain dead donors treated in the university hospitals of Aachen, Bielefeld, Bonn, Essen, Düsseldorf, Cologne and Münster between June 2020 and July 2021. 300 potential brain dead donors were identified. Donation was utilized in 69 cases (23%). Refused consent (n = 190), and failed utilization despite consent (n = 41) were reasons for a donation not realized. Consent was significantly higher in potential donors with a known attitude towards donation (n = 94) compared to a decision by family members (n = 195) (49% vs. 33%, p = 0.012). The potential donor´s age, status of interviewer, and the timing of the interview with decision-makers had no influence on consent rates, and it was comparable between hospitals. Refused consent was the predominant reason for a donation not utilized. Consent rate was lower than in surveys, only a known attitude towards donation had a significant positive influence. This indicates that survey results do not translate well into everyday clinical practice and promoting a previously documented decision on organ donation is important.

Pupillary Pain Index Predicts Postoperative Pain but Not the Effect of Peripheral Regional Anaesthesia in Patients Undergoing Total Hip or Total Knee Arthroplasty: An Observational Study.

Background and Objectives: The pupillary pain index (PPI) allows the evaluation of intraoperative nociception by measuring pupillary reaction after a localized electrical stimulus. It was the objective of this observational cohort study to investigate the pupillary pain index (PPI) as a method to evaluate the fascia iliaca block (FIB) or adductor canal block (ACB) sensory areas during general anaesthesia in orthopaedic patients with lower-extremity joint replacement surgery. Materials and Methods: Orthopaedic patients undergoing hip or knee arthroplasty were included. After anaesthesia induction, patients received an ultrasound-guided single-shot FIB or ACB with 30 mL and 20 mL of 0.375% ropivacaine, respectively. Anaesthesia was maintained with isoflurane or propofol/remifentanil. The first PPI measurements were performed after anaesthesia induction and before block insertion, the second at the end of surgery. Pupillometry scores were evaluated in the area of the femoral or saphenous nerve (target) and C3 dermatome (control). Primary outcomes were differences between PPIs before and after peripheral block insertion as well as the relationship between PPIs and postoperative pain scores; secondary outcomes were the relationship between PPIs and opioid requirements after surgery. Results: PPI decreased significantly from the first to the second measurement (4.17 ± 2.7 vs. 1.6 ± 1.2, p < 0.001 for target; 4.46 ± 2.7 vs. 2.17 ± 2.1, p < 0.001 for control). Control and target measurements did not show significant differences. A linear regression analysis showed that early postoperative pain scores could be predicted with intraoperative piritramide with improved prediction after adding PPI scores, PCA opioids and surgery type. Forty-eight-hour pain scores at rest and in movement were correlated with intraoperative piritramide and control PPI after the PNB in movement and with second-postoperative-day opioids and target PPI scores before block insertion, respectively. Conclusions: While the effect of an FIB and ACB could not be shown with PPI postoperative pain scores due to a large effect of opioids, perioperative PPI was shown to be associated with postoperative pain. These results suggest that preoperative PPI may be used to predict postoperative pain.

Risk assessment of perioperative neurocognitive disorders, where are we now?

PURPOSE OF REVIEW: Perioperative neurocognitive disorders (PNDs) are among the most frequent complications after surgery and are associated with considerable morbidity and mortality. We analysed the recent literature regarding risk assessment of PND. RECENT FINDINGS: Certain genetic variants of the cholinergic receptor muscarinic 2 and 4, as well as a marked degree of frailty but not the kind of anaesthesia (general or spinal) are associated with the risk to develop postoperative delirium (POD). Models predict POD with a discriminative power, for example, area under the receiver operating characteristics curve between 0.52 and 0.94. SUMMARY: Advanced age as well as preexisting cognitive, functional and sensory deficits remain to be the main risk factors for the development of PND. Therefore, aged patients should be routinely examined for both preexisting and new developing deficits, as recommended in international guidelines. Appropriate tests should have a high discrimination rate, be feasible to be administered by staff that do not require excessive training, and only take a short time to be practical for a busy outpatient clinic. Models to predict PND, should be validated appropriately (and externally if possible) and should not contain a too large number of predictors to prevent overfitting of models.

Controlled arterial hypotension during resection of cerebral arteriovenous malformations.

BACKGROUND: Resection of cerebral arteriovenous malformations (AVM) is technically demanding because of size, eloquent location or diffuse nidus. Controlled arterial hypotension (CAH) could facilitate haemostasis. We performed a study to characterize the duration and degree of CAH and to investigate its association with blood loss and outcome. METHODS: We retrospectively analysed intraoperative arterial blood pressure of 56 patients that underwent AVM-resection performed by the same neurosurgeon between 2003 and 2012. Degree of CAH, AVM size, grading and neurological outcome were studied. Patients were divided into two groups, depending on whether CAH was performed (hypotension group) or not (control group). RESULTS: The hypotension group consisted of 28 patients, which presented with riskier to treat AVMs and a higher Spetzler-Martin grading. CAH was achieved by application of urapidil, increasing anaesthetic depth or a combination thereof. Systolic and mean arterial blood pressure were lowered to 82 ± 7 and 57 ± 7 mmHg, respectively, for a median duration of 58 min [25% percentile: 26 min.; 75% percentile: 107 min]. In the hypotension group, duration of surgery (4.4 ± 1.3 h) was significantly (p <  0.001) longer, and median blood loss (500 ml) was significantly (p = 0.002) higher than in the control group (3.3 ± 0.9 h and 200 ml, respectively). No case fatalities occurred. CAH was associated with a higher amount of postoperative neurological deficits. CONCLUSIONS: Whether CAH caused neurological deficits or prevented worse outcomes could be clarified by a prospective randomised study, which is regarded as ethically problematic in the context of bleeding. CAH should only be used after strict indication and should be applied as mild and short as possible.

Challenges and pitfalls in anesthesia for electroconvulsive therapy.

Electroconvulsive therapy (ECT) refers to the application of electricity to the patients' scalp to treat psychiatric disorders, most notably, treatment-resistant depression. It is a safe, effective, and evidence-based therapy that is performed with general anesthesia. Muscle relaxation is used to prevent injuries related to the tonic-clonic seizure caused by ECT. Hypnotics are administered to induce amnesia and unconsciousness, so that, patients do not experience the period of muscle relaxation, while the generalized seizure is left unnoticed. For the anesthesiologist, ECT is associated with the challenges and pitfalls that are related to informed consent, social acceptance of ECT, airway management (especially in COVID-19 patients), and the interaction between ventilation and anesthetics from one viewpoint, and seizure induction and maintenance from another. The exact mode of action of the therapy is as unknown as the optimal choice or combination of anesthetics used.

Gene expression in the Angiopoietin/TIE axis is altered in peripheral tissue of ovarian cancer patients: A prospective observational study.

AIMS: Clinical studies suggest altered systemic vascular biology in cancer patients. We assessed expression patterns of endothelial activation- and vascular leakage-related genes in tumor as well as in tumor-free peripheral tissues from patients with and without ovarian cancer (OC). MAIN METHODS: Patients being scheduled for laparotomy for either gynecologic benign diagnosis (n = 10) or for advanced-stage OC (n = 22) were prospectively recruited to this observational study. Serum samples were taken preoperatively, and tissue samples were taken from peripheral abdominal wall musculature, tumor-free peritoneum and the tumor itself. KEY FINDINGS: Patients in OC group received significantly more fluid per time intraoperatively (p = 0.01). IL-8 and MCP-1/CCL2, VCAM-1 (CD 106) and ICAM-1 (CD 54) as well as Thrombomodulin were significantly increased in cancer patients' serum at baseline (p = 0.03). Expression of distinct vascular leakage-related genes (Angiopoietin-1 (ANG-1), ANG-2, TIE2, VEGFR1, VEGFR2) was significantly altered in tumor tissue of OC patients (p = 0.003), while in tumor-free peritoneal tissue, ANG-2/1 expression ratio was more than doubled in OC group (p = 0.03). In peripheral musculature, particularly genes from the ANG/TIE axis were significantly changed in OC patients (p = 0.005), suggesting a distinct vascular leakage-related genotype. Gene expression changes in OC patients were significantly associated with the postoperative fluid balance (p = 0.03). SIGNIFICANCE: Altered expression of barrier dysfunction- and angiogenesis-associated genes from the ANG/TIE axis was detected not only in tumor but also in peripheral tissues of cancer patients. This may contribute to a systemic vascular leakage-related genotype.

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

Differential modulation of endothelial cell function by fresh frozen plasma.

AIMS: In vivo studies suggest a positive influence of fresh frozen plasma (FFP) on endothelial properties and vascular barrier function, leading to improved outcomes in animal sepsis models as well as in major abdominal surgery. However, those effects are incompletely described. It was our aim to evaluate in vitro effects of FFP on endothelial key functions and to identify underlying mechanisms. MATERIALS AND METHODS: Human pulmonary microvascular endothelial cells (HPMECs) were prestimulated with LPS, followed by incubation with FFP. Permeability for FITC-dextran was assessed, and intercellular gap formation was visualized. NF-κB nuclear translocation and expression of pro-inflammatory, pro-adhesion, and leakage-related genes were evaluated, and monocyte adhesion to ECs was assessed. Intracellular cAMP levels as well as phosphorylation of functional proteins were analyzed. In patients undergoing major abdominal surgery, Syndecan-1 serum levels were assessed prior to and following FFP transfusion. KEY FINDINGS: Post-incubation of HPMVECs with FFP increased intracellular cAMP levels that had been decreased by preceding LPS stimulation. On one hand, this reduced endotoxin-mediated upregulation of IL-8, ICAM-1, VCAM-1, VEGF, and ANG-2. Impaired phosphorylation of functional proteins was restored, and intercellular cohesion and barrier function were rescued. On the other hand, NF-κB nuclear translocation as well as monocyte adhesion was markedly increased by the combination of LPS and FFP. Syndecan-1 serum levels were lower in surgery patients that were transfused with FFP compared to those that were not. SIGNIFICANCE: Our data provide evidence for a differential modulation of crucial endothelial properties by FFP, potentially mediated by elevation of intracellular cAMP levels.

Dynamic changes of angiopoietins and endothelial nitric oxide supply during fluid resuscitation for major gyn-oncological surgery: a prospective observation.

BACKGROUND: Despite goal-directed hemodynamic therapy, vascular function may deteriorate during surgery for advanced abdominal tumor masses. Fluid administration has been shown to be associated with distinct changes in serum levels of functional proteins. We sought to determine how serum total protein and angiopoietin (ANG) levels change during major abdominal tumor surgery. In addition, ex vivo endothelial nitric oxide synthase (eNOS) activation as well as NO bioavailability in vivo were assessed. METHODS: 30 patients scheduled for laparotomy for late-stage ovarian or uterine cancer were prospectively included. Advanced hemodynamic monitoring as well as protocol-driven goal-directed fluid optimization were performed. Total serum protein, ANG-1, -2, and soluble TIE2 were determined pre-, intra-, and postoperatively. Phosphorylation of eNOS was assessed in microvascular endothelial cells after incubation with patient serum, and microvascular reactivity was determined in vivo by near-infrared spectroscopy and arterial vascular occlusion. RESULTS: Cardiac output as well as preload gradually decreased during surgery and were associated with a median total fluid intake of 12.8 (9.7-15.4) mL/kg*h and a postoperative fluid balance of 6710 (4113-9271) mL. Total serum protein decreased significantly from baseline (66.5 (56.4-73.3) mg/mL) by almost half intraoperatively (42.7 (36.8-51.5) mg/mL, p < 0.0001) and remained at low level. While ANG-1 showed no significant dilutional change (baseline: 12.7 (11.9-13.9) ng/mL, postop.: 11.6 (10.8 -13.5) ng/mL, p = 0.06), serum levels of ANG-2 were even increased postoperatively (baseline: 2.2 (1.6-2.6) ng/mL vs. postop.: 3.4 (2.3-3.8) ng/mL, p < 0.0001), resulting in a significant shift in ANG-2 to ANG-1 ratio. Ex vivo phosphorylation of eNOS was decreased depending on increased ANG-2 levels and ANG-2/1 ratio (Spearman r = - 0.37, p = 0.007). In vivo, increased ANG-2 levels were associated with impaired capillary recruitment and NO bioavailability (Spearman r = - 0.83, p = 0.01). CONCLUSIONS: Fluid resuscitation-associated changes in serum vascular mediator profile during abdominal tumor surgery were accompanied by impaired eNOS activity ex vivo as well as reduced NO bioavailability in vivo. Our results may explain disturbed microvascular function in major surgery despite goal-directed hemodynamic optimization.

Accuracy of the non-invasive Tcore™ temperature monitoring system to measure body core temperature in abdominal surgery.

An accurate determination of body core temperature is crucial during surgery in order to avoid and treat hypothermia, which is associated with poor outcome. In a prospective observational study, we evaluated the suitability of the Tcore™ device (Drägerwerk AG & Co. KGaA, Lübeck, Germany)-a non-invasive thermometer-to accurately determine core body temperature. In patients undergoing surgery for ovarian cancer, core body temperature (CBT) was determined with the Tcore™ sensor attached to the forehead and compared with blood temperature (Tblood) as measured within the femoro-iliacal artery. Both temperatures were recorded every 10 s and the measurement error was calculated. 57,302 data pairs of CBT and Tblood were obtained in 22 patients. In a repeated-measurements version of the Bland and Altman test, a bias of - 0.02 °C and 95% limits of agreement of - 0.48 to 0.44 °C were calculated. In a population analysis, a median absolute error of 0 [- 0.1; + 0.1] °C, a bias of 0 [- 0.276; 0.271] % and an inaccuracy of 0.276 [0.274; 0.354] % was determined. Although the Tcore™ sensor was attached to the frontal skin, it provided an accurate measurement of core body temperature in the investigated intraoperative setting.

Supraglottic devices for airway management in awake craniotomy.

Awake craniotomy is a unique technique utilized for mapping neuro and motor function during neurosurgical procedures close to eloquent brain tissue. Since active communication is required only during surgical manipulation of eloquent brain tissue and the patient is "sedated" during other parts of the procedure, different methods for anesthesia management have been explored. Furthermore, airway management ranges from spontaneous breathing to oro or nasotracheal intubation. Case reports have described the use of laryngeal masks (LMs) previously; however, its safety compared to tracheal intubation has not been assessed.We conducted a retrospective analysis of 30 patients that underwent awake craniotomy for tumor surgery to compare the feasibility and safety of different airway management strategies. Nasal fiberoptic intubation (FOI) was performed in 21 patients while 9 patients received LM for airway management. Ventilation, critical events, and perioperative complications were evaluated.Cannot intubate situation occurred in 4 cases reinserting the tube after awake phase, while no difficulties were described reinserting the LM (P < .0001). Furthermore, duration of mechanical ventilation after tumor removal was significantly lower in the LM group compared to FOI group (62 ±â€Š24 vs. 339 ±â€Š82 [min] mean ±â€Šsem, P < .0001). Postoperatively, 2 patients in each group were diagnosed with and treated for respiratory complications including pneumonia, without statistical significance between groups.In summary, LM is a feasible airway management method for patients undergoing awake craniotomy, resulting in reduced ventilation duration compared to FOI procedure.

Network of Mediators for Vascular Inflammation and Leakage Is Dysbalanced during Cytoreductive Surgery for Late-Stage Ovarian Cancer.

BACKGROUND: Cytoreductive surgery (CS) in late-stage ovarian cancer patients is often challenging due to extensive volume shifts, and high fluid intake may provoke postoperative complications. Expression of vasoactive mediators is altered in cancer patients, which may affect systemic vascular function. We sought to assess how serum levels of vasoactive markers and mediators change during CS in ovarian cancer. METHODS: Following IRB approval and informed consent, pre- and postoperative serum samples were analyzed in 26 late-stage ovarian cancer patients using multiplex protein arrays and ELISA. RESULTS: The proinflammatory cytokines and chemokines IL-6, IL-8, and CCL2 were significantly elevated after 24 hrs compared to the baseline values, with IL-6 and IL-8 being most prominently increased. While ANGPT1 remained unchanged after surgery, its competitive antagonist ANGPT2 was significantly increased. In contrast, serum levels of the ANGPT receptor TIE2 were decreased to 0.6 of the baseline values. While VEGF-D, E-selectin, P-selectin, ICAM-1, and PECAM-1 remained unchanged, serum activity of both thrombomodulin and syndecan-1 was significantly increased following surgery. CONCLUSION: We identified a regulatory network of acute-phase reaction during CS in late-stage ovarian cancer. This suggests that IL-6 exerts positive regulation of other proinflammatory mediators and, by upregulating ANGPT2 and suppressing ANGPT1, induces a serum profile that promotes vascular leakage. This may contribute to the observed hemodynamic alterations during CS procedures.

Impact of PReOperative Midazolam on OuTcome of Elderly patients (I-PROMOTE): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Premedication of surgical patients with benzodiazepines has become questionable regarding risk-benefit ratio and lack of evidence. Though preoperative benzodiazepines might alleviate preoperative anxiety, a higher risk for adverse events is described, particularly for elderly patients (≥ 65 years). Several German hospitals already withhold benzodiazepine premedication from elderly patients, though evidence for this approach is lacking. The patient-centred outcome known as global postoperative patient satisfaction is recognised as a substantial quality indicator of anaesthesia care incorporated by the American Society of Anesthesiologists. Therefore, we aim to assess whether the postoperative patient satisfaction after premedication with placebo compared to the preoperative administration of 3.75 mg midazolam in elderly patients differs. METHODS: This study is a multicentre, randomised, placebo-controlled, double-blinded, two-arm parallel, interventional trial, conducted in nine German hospitals. In total 614 patients (≥ 65-80 years of age) undergoing elective surgery with general anaesthesia will be randomised to receive either 3.75 mg midazolam or placebo. The primary outcome (global patient satisfaction) will be assessed with the validated EVAN-G questionnaire on the first postoperative day. Secondary outcomes will be assessed until the first postoperative day and then 30 days after surgery. They comprise among other things: functional and cognitive recovery, postoperative delirium, health-related quality of life assessment, and mortality or new onset of serious cardiac or pulmonary complications, acute stroke, or acute kidney injury. Analysis will adhere to the intention-to-treat principle. The primary outcome will be analysed with the use of mixed linear models including treatment effect and study centre as factors and random effects for blocks. Exploratory adjusted and subgroup analyses of the primary and secondary outcomes with regard to gender effects, frailty, pre-operative anxiety level, patient demographics, and surgery experience will also be performed. DISCUSSION: This is, to the best of our knowledge, the first study analysing patient satisfaction after premedication with midazolam in elderly patients. In conclusion, this study will provide high-quality data for the decision-making process regarding premedication in elderly surgical patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03052660 . Registered on 14 February 2017. EudraCT 2016-004555-79 .