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The anesthetist's choice of inhalational vs. intravenous anesthetics has no impact on survival of glioblastoma patients.

ABSTRACT: Recent data suggest that the type of anesthesia used during the resection of solid tumors impacts the long-term survival of patients favoring total-intravenous-anesthesia (TIVA) over inhalative-anesthesia (INHA). Here we sought to query this impact on survival in patients undergoing resection of glioblastoma (GBM). All patients receiving elective resection of a newly diagnosed, isocitrate-dehydrogenase-1-(IDH1)-wildtype GBM under general anesthesia between January 2010 and June 2017 in the Department of Neurosurgery, Heidelberg University Hospital, were included. Patients were grouped according to the applied anesthetic technique. To adjust for potential prognostic confounders, patients were matched in a 1:2 ratio (TIVA vs. INHA), taking into account the known prognostic factors: age, extent of resection, O-6-methylguanine-DNA-methyltransferase-(MGMT)-promoter-methylation-status, pre-operative Karnofsky-performance-index and adjuvant radio- and chemotherapy. The primary endpoint was progression-free-survival (PFS) and the secondary endpoint was overall-survival (OS). In the study period, 576 patients underwent resection of a newly diagnosed, IDH-wildtype GBM. Patients with incomplete follow-up-data, on palliative treatment, having emergency or awake surgery; 54 patients remained in the TIVA-group and 417 in the INHA-group. After matching, 52 patients remained in the TIVA-group and 92 in the INHA-group. Median PFS was 6 months in both groups. The median OS was 13.5 months in the TIVA-group and 13.0 months in the INHA-group. No significant survival differences associated with the type of anesthesia were found either before or after adjustment for known prognostic factors. This retrospective study supports the notion that the current anesthetic approaches employed during the resection of IDH-wildtype GBM do not impact patient survival.

SUBMITTER: Schmoch T

PROVIDER: S-EPMC8490243 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundStudies indicate that patients can be "seeded" with their own cancer cells during oncologic surgery and that the immune response to these circulating cancer cells might influence the risk of cancer recurrence. Preliminary data from animal studies and some retrospective analyses suggest that anesthetic technique might affect the immune response during surgery and hence the risk of cancer recurrence. In 2015, experts called for prospective scientific inquiry into whether anesthetic technique used in cancer resection surgeries affects cancer-related outcomes such as recurrence and mortality. Therefore, we designed a pragmatic phase 3 multicenter randomized controlled trial (RCT) called General Anesthetics in Cancer Resection (GA-CARES).MethodsAfter clinical trial registration and institutional review board approval, patients providing written informed consent were enrolled at five sites in New York (NY) State. Eligible patients were adults with known or suspected cancer undergoing one of eight oncologic surgeries having a high risk of cancer recurrence. Exclusion criteria included known or suspected history of malignant hyperthermia or hypersensitivity to either propofol or volatile anesthetic agents. Patients were randomized (1:1) stratified by center and surgery type using REDCap to receive either propofol or volatile agent for maintenance of general anesthesia (GA). This pragmatic trial, which seeks to assess the potential impact of anesthetic type in "real world practice", did not standardize any aspect of patient care. However, potential confounders, e.g., use of neuroaxial anesthesia, were recorded to confirm the balance between study arms. Assuming a 5% absolute difference in 2-year overall survival rates (85% vs 90%) between study arms (primary endpoint, minimum 2-year follow-up), power using a two-sided log-rank test with type I error of 0.05 (no planned interim analyses) was calculated to be 97.4% based on a target enrollment of 1800 subjects. Data sources include the National Death Index (gold standard for vital status in the USA), NY Cancer Registry, and electronic harvesting of data from electronic medical records (EMR), with minimal manual data abstraction/data entry.DiscussionEnrollment has been completed (n = 1804) and the study is in the follow-up phase. This unfunded, pragmatic trial, uses a novel approach for data collection focusing on electronic sources.Trial registrationRegistered (NCT03034096) on January 27, 2017, prior to consent of the first patient on January 31, 2017.

Project description:Elderly patients who have solid organ cancer often receive surgery. Some of them may develop delirium after surgery and delirium development is associated with worse outcomes. Furthermore, despite all of the advances in medical care, the long-term survival in cancer patients is far from optimal. Evidences suggest that choice of anaesthetics during surgery, that is, either inhalational or intravenous anaesthetics, may influence outcomes. However, the impact of general anaesthesia type on the occurrence of postoperative delirium is inconclusive. Although retrospective studies suggest that propofol-based intravenous anaesthesia was associated with longer survival after cancer surgery when compared with inhalational anaesthesia, prospective studies as such are still lacking. The purposes of this randomised controlled trial are to test the hypotheses that when compared with sevoflurane-based inhalational anaesthesia, propofol-based intravenous anaesthesia may reduce the incidence of early delirium and prolong long-term survival in elderly patients after major cancer surgery.This is a multicentre, open-label, randomised controlled trial with two parallel arms. 1200 elderly patients (?65 years but <90 years) who are scheduled to undergo major cancer surgery (with predicted duration ?2?hours) are randomised to receive either sevoflurane-based inhalational anaesthesia or propofol-based intravenous anaesthesia. Other anaesthetics and supplemental drugs including sedatives, opioids and muscle relaxants are administered in both arms according to routine practice. The primary early outcome is the incidence of 7-day delirium after surgery and the primary long-term outcome is the duration of 3-year survival after surgery.The study protocol has been approved by the Clinical Research Ethics Committees of Peking University First Hospital (2015[869]) and all participating centres. The results of early and long-term outcomes will be analysed and reported separately.ChiCTR-IPR-15006209; NCT02662257; NCT02660411.

Project description:BackgroundIschemic preconditioning is an important intrinsic mechanism for neuroprotection. Preconditioning can also be achieved by exposure of neurons to K+ channel-opening drugs that act on adenosine triphosphate-sensitive K+ (K(ATP)) channels. However, these agents do not readily cross the blood-brain barrier. Inhalational anesthetics which easily partition into brain have been shown to precondition various tissues. Here, the authors explore the neuronal preconditioning effect of modern inhalational anesthetics and investigate their effects on K(ATP) channels.MethodsNeuronal-glial cocultures were exposed to inhalational anesthetics in a preconditioning paradigm, followed by oxygen-glucose deprivation. Increased cell survival due to preconditioning was quantified with the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction test. Recombinant plasmalemmal K(ATP) channels of the main neuronal type (Kir6.2/SUR1) were expressed in HEK293 cells, and the effects of anesthetics were evaluated in whole cell patch clamp recordings.ResultsBoth sevoflurane and the noble gas xenon preconditioned neurons at clinically used concentrations. The effect of sevoflurane was independent of K(ATP) channel activation, whereas the effect of xenon required the opening of plasmalemmal K(ATP) channels. Recombinant K(ATP) channels were activated by xenon but inhibited by halogenated volatiles. Modulation of mitochondrial K-ATP channels did not affect the activity of K(ATP) channels, thus ruling out an indirect effect of volatiles via mitochondrial channels.ConclusionsThe preconditioning properties of halogenated volatiles cannot be explained by their effect on K(ATP) channels, whereas xenon preconditioning clearly involves the activation of these channels. Therefore, xenon might mimic the intrinsic mechanism of ischemic preconditioning most closely. This, together with its good safety profile, might suggest xenon as a viable neuroprotective agent in the clinical setting.

Project description:Background and aimTotal intravenous anesthesia (TIVA) has proven advantage over inhalational anesthesia in terms of stable hemodynamic, eco-friendly, and good recovery profile, but apprehension regarding adequate depth of anesthesia and intraoperative recall is still pertaining. This study aims to compare propofol-dexmedetomidine-based TIVA with sevoflurane-based inhalational anesthesia in modified radical mastectomy in terms of depth of anesthesia, intraoperative recall, recovery profile, and hemodynamic status.Settings and designThis prospective randomized controlled study was conducted at a tertiary care center over a time frame of 1 year.MethodologyIn this randomized controlled study, 100 patients were randomly distributed into two groups: TIVA (Group T) and inhalational anesthesia (Group I). Group T patients received injection dexmedetomidine: 1 μg.kg-1 over 10 min followed by 0.7 μg.kg-1.h-1 and injection propofol: 25-100 μg.kg-1.min-1. Ventilation was maintained with oxygen-air gas flow. In Group I, patients were ventilated with nitrous oxide-oxygen (50:50) and sevoflurane. Rest of anesthesia for both the groups was same. Primary objective was to achieve adequate depth of anesthesia as monitored by intraoperative bispectral index value (BIS, 40-60). Hemodynamic variables, recovery profile, and amount of individual anesthetic agent consumed were recorded for comparison between two groups. For comparison of scale variables between two groups, independent sample t-test for significant difference between two sample means has been followed.ResultsIntraoperative BIS and hemodynamic variables were comparable (P > 0.05). Emergence time was 5.10 min in the TIVA group versus 8.38 min in the inhalational group (P = 0.00). Modified Aldrete score was comparable in two groups (P > 0.05). Cost of TIVA agents consumed per patient was 40% lesser than inhalational agents.ConclusionTIVA maintains adequate depth of anesthesia along with stable hemodynamic and good recovery profile, at low cost in an eco-friendly manner.

Project description:BackgroundLocal and volatile anesthetics are widely used for surgery. It is not known whether anesthetics impinge on the orchestrated events in spontaneous resolution of acute inflammation. Here we investigated whether a commonly used local anesthetic (lidocaine) and a widely used inhaled anesthetic (isoflurane) impact the active process of resolution of inflammation.Methods and findingsUsing murine peritonitis induced by zymosan and a systems approach, we report that lidocaine delayed and blocked key events in resolution of inflammation. Lidocaine inhibited both PMN apoptosis and macrophage uptake of apoptotic PMN, events that contributed to impaired PMN removal from exudates and thereby delayed the onset of resolution of acute inflammation and return to homeostasis. Lidocaine did not alter the levels of specific lipid mediators, including pro-inflammatory leukotriene B(4), prostaglandin E(2) and anti-inflammatory lipoxin A(4), in the cell-free peritoneal lavages. Addition of a lipoxin A(4) stable analog, partially rescued lidocaine-delayed resolution of inflammation. To identify protein components underlying lidocaine's actions in resolution, systematic proteomics was carried out using nanospray-liquid chromatography-tandem mass spectrometry. Lidocaine selectively up-regulated pro-inflammatory proteins including S100A8/9 and CRAMP/LL-37, and down-regulated anti-inflammatory and some pro-resolution peptides and proteins including IL-4, IL-13, TGF-â and Galectin-1. In contrast, the volatile anesthetic isoflurane promoted resolution in this system, diminishing the amplitude of PMN infiltration and shortening the resolution interval (Ri) approximately 50%. In addition, isoflurane down-regulated a panel of pro-inflammatory chemokines and cytokines, as well as proteins known to be active in cell migration and chemotaxis (i.e., CRAMP and cofilin-1). The distinct impact of lidocaine and isoflurane on selective molecules may underlie their opposite actions in resolution of inflammation, namely lidocaine delayed the onset of resolution (T(max)), while isoflurane shortened resolution interval (Ri).ConclusionsTaken together, both local and volatile anesthetics impact endogenous resolution program(s), altering specific resolution indices and selective cellular/molecular components in inflammation-resolution. Isoflurane enhances whereas lidocaine impairs timely resolution of acute inflammation.

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The anesthetist's choice of inhalational vs. intravenous anesthetics has no impact on survival of glioblastoma patients.

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