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2.
J Pers Med ; 14(2)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38392652

ABSTRACT

More than 25% of older adults in Europe have diabetes mellitus. It is estimated that 45% of patients with diabetes are currently undiagnosed, which is a known risk factor for perioperative morbidity. We investigated whether routine HbA1c screening in older adult patients undergoing surgery would identify patients with undiagnosed diabetes. We included patients aged ≥65 years without a diagnosis of diabetes who visited the preoperative assessment clinic at the Amsterdam University Medical Center and underwent HbA1c screening within three months before surgery. Patients undergoing cardiac surgery were excluded. We assessed the prevalence of undiagnosed diabetes (defined as HbA1c ≥ 48 mmol·mol-1) and prediabetes (HbA1c 39-47 mmol·mol-1). Using a multivariate regression model, we analysed the ability of HbA1c to predict days alive and at home within 30 days after surgery. From January to December 2019, we screened 2015 patients ≥65 years at our clinic. Of these, 697 patients without a diagnosis of diabetes underwent HbA1c screening. The prevalence of undiagnosed diabetes and prediabetes was 3.7% (95%CI 2.5-5.4%) and 42.9% (95%CI 39.2-46.7%), respectively. Preoperative HbA1c was not associated with days alive and at home within 30 days after surgery. In conclusion, we identified a small number of patients with undiagnosed diabetes and a high prevalence of prediabetes based on preoperative HbA1c screening in a cohort of older adults undergoing non-cardiac surgery. The relevance of prediabetes in the perioperative setting is unclear. Screening for HbA1c in older adult patients undergoing non-cardiac surgery does not appear to help predict postoperative outcome.

3.
J Clin Med ; 13(2)2024 Jan 17.
Article in English | MEDLINE | ID: mdl-38256668

ABSTRACT

BACKGROUND: A post-anaesthesia care unit (PACU) may improve postoperative care compared with intermediate care units (IMCU) due to its dedication to operative care and an individualized duration of postoperative stay. The effects of transition from IMCU to PACU for postoperative care following intermediate to high-risk noncardiac surgery on length of hospital stay, intensive care unit (ICU) utilization, and postoperative complications were investigated. METHODS: This single-centre interrupted time series analysis included patients undergoing eleven different noncardiac surgical procedures associated with frequent postoperative admissions to an IMCU or PACU between January 2018 and March 2019 (IMCU episode) and between October 2019 and December 2020 (PACU episode). Primary outcome was hospital length of stay, secondary outcomes included postoperative complications and ICU admissions. RESULTS: In total, 3300 patients were included. The hospital length of stay was lower following PACU admission compared to IMCU admission (IMCU 7.2 days [4.2-12.0] vs. PACU 6.0 days [3.6-9.1]; p < 0.001). Segmented regression analysis demonstrated that the introduction of the PACU was associated with a decrease in hospital length of stay (GMR 0.77 [95% CI 0.66-0.91]; p = 0.002). No differences between episodes were detected in the number of postoperative complications or postoperative ICU admissions. CONCLUSIONS: The introduction of a PACU for postoperative care of patients undergoing intermediate to high-risk noncardiac surgery was associated with a reduction in the length of stay at the hospital, without increasing postoperative complications.

4.
Redox Biol ; 69: 102979, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38061206

ABSTRACT

BACKGROUND: Empagliflozin (EMPA) ameliorates reactive oxygen species (ROS) generation in human endothelial cells (ECs) exposed to 10 % stretch, but the underlying mechanisms are still unclear. Pathological stretch is supposed to stimulate protein kinase C (PKC) by increasing intracellular calcium (Ca2+), therefore activating nicotinamide adenine dinucleotide phosphate oxidase (NOX) and promoting ROS production in human ECs. We hypothesized that EMPA inhibits stretch-induced NOX activation and ROS generation through preventing PKC activation. METHODS: Human coronary artery endothelial cells (HCAECs) were pre-incubated for 2 h before exposure to cyclic stretch (5 % or 10 %) with either vehicle, EMPA or the PKC inhibitor LY-333531 or PKC siRNA. PKC activity, NOX activity and ROS production were detected after 24 h. Furthermore, the Ca2+ chelator BAPTA-AM, NCX inhibitor ORM-10962 or NCX siRNA, sodium/potassium pump inhibitor ouabain and sodium hydrogen exchanger (NHE) inhibitor cariporide were applied to explore the involvement of the NHE/Na+/NCX/Ca2+ in the ROS inhibitory capacity of EMPA. RESULTS: Compared to 5 % stretch, 10 % significantly increased PKC activity, which was reduced by EMPA and PKC inhibitor LY-333531. EMPA and LY-333531 showed a similar inhibitory capacity on NOX activity and ROS generation induced by 10 % stretch, which was not augmented by combined treatment with both drugs. PKC-ß knockdown inhibits the NOX activation induced by Ca2+ and 10 % stretch. BAPTA, pharmacologic or genetic NCX inhibition and cariporide reduced Ca2+ in static HCAECs and prevented the activation of PKC and NOX in 10%-stretched cells. Ouabain increased ROS generation in cells exposed to 5 % stretch. CONCLUSION: EMPA reduced NOX activity via attenuation of the NHE/Na+/NCX/Ca2+/PKC axis, leading to less ROS generation in HCAECs exposed to 10 % stretch.


Subject(s)
Benzhydryl Compounds , Coronary Vessels , Endothelial Cells , Glucosides , Guanidines , Indoles , Maleimides , Sulfones , Humans , Endothelial Cells/metabolism , Reactive Oxygen Species/metabolism , Coronary Vessels/metabolism , Protein Kinase C/metabolism , Ouabain/metabolism , Oxidative Stress , Sodium-Hydrogen Exchangers/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/metabolism
5.
Eur J Radiol ; 170: 111242, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38043382

ABSTRACT

PURPOSE: Cerebral arterial gas embolism (CAGE) occurs when air or medical gas enters the systemic circulation during invasive procedures and lodges in the cerebral vasculature. Non-contrast computer tomography (CT) may not always show intracerebral gas. CT perfusion (CTP) might be a useful adjunct for diagnosing CAGE in these patients. METHODS: This is a retrospective single-center cohort study. We included patients who were diagnosed with iatrogenic CAGE and underwent CTP within 24 h after onset of symptoms between January 2016 and October 2022. All imaging studies were evaluated by two independent radiologists. CTP studies were scored semi-quantitatively for perfusion abnormalities (normal, minimal, moderate, severe) in the following parameters: cerebral blood flow, cerebral blood volume, time-to-drain and time-to-maximum. RESULTS: Among 27 patient admitted with iatrogenic CAGE, 15 patients underwent CTP within the designated timeframe and were included for imaging analysis. CTP showed perfusion deficits in all patients except one. The affected areas on CTP scans were in general located bilaterally and frontoparietally. The typical pattern of CTP abnormalities in these areas was hypoperfusion with an increased time-to-drain and time-to-maximum, and a corresponding minimal decrease in cerebral blood flow. Cerebral blood volume was mostly unaffected. CONCLUSION: CTP may show specific perfusion defects in patients with a clinical diagnosis of CAGE. This suggests that CTP may be supportive in diagnosing CAGE in cases where no intracerebral gas is seen on non-contrast CT.


Subject(s)
Brain Ischemia , Embolism, Air , Stroke , Humans , Retrospective Studies , Tomography, X-Ray Computed/methods , Embolism, Air/diagnostic imaging , Cohort Studies , Perfusion , Iatrogenic Disease , Perfusion Imaging/methods , Cerebrovascular Circulation/physiology
6.
Trials ; 24(1): 660, 2023 Oct 11.
Article in English | MEDLINE | ID: mdl-37821994

ABSTRACT

BACKGROUND: As a result of increased life expectancy and improved care for patients suffering from chronic disease, the number of patients with multimorbidity requiring surgical intervention is increasing. For complex surgical patients, it is essential to balance the potential benefits of surgical treatment against the risk of permanent loss of functional capacity and quality of life due to complications. European and US guidelines on perioperative care recommend preoperative multidisciplinary team (MDT) discussions for high-risk noncardiac surgical patients. However, the evidence underlying benefits from preoperative MDT meetings with all relevant perioperative specialties present is limited. The current study aims to investigate the effect of implementation of preoperative MDT discussions for high-risk patients undergoing noncardiac surgery on serious adverse events. METHODS/DESIGN: PREPARATION is a stepped-wedge cluster randomized trial in 14 Dutch hospitals without currently established preoperative MDT meeting. The intervention, preoperative MDT meetings, will be implemented sequentially with seven blocks of 2 hospitals switching from control (preoperative screening as usual) to the intervention every 3 months. Each hospital will be randomized to one of seven blocks. We aim to include 1200 patients. The primary outcome is the incidence of serious adverse events at 6 months. Secondary outcomes include (cost)effectiveness, functional outcome, and quality of life for up to 12 months. DISCUSSION: PREPARATION is the first study to assess the effectiveness of a preoperative MDT meeting for high-risk noncardiac surgical patients in the presence of an anesthesiologist. If the results suggest that preoperative MDT discussions for high-risk patients are (cost)-effective, the current study facilitates implementation of preoperative MDT meetings in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT05703230. Registered on 11/09/2022.


Subject(s)
Medicine , Quality of Life , Humans , Adult , Perioperative Care , Hospitals , Patient Care Team
7.
J Clin Med ; 12(17)2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37685829

ABSTRACT

Infective endocarditis is a challenging condition to manage, requiring collaboration among various medical professionals. Interdisciplinary teamwork within endocarditis teams is essential. About half of the patients diagnosed with the disease will ultimately have to undergo cardiac surgery. As a result, it is vital for all healthcare providers involved in the perioperative period to have a comprehensive understanding of the unique features of infective endocarditis, including clinical presentation, echocardiographic signs, coagulopathy, bleeding control, and treatment of possible organ dysfunction. This narrative review provides a summary of the current knowledge on the incidence of complications and their management in the perioperative period in patients with infective endocarditis.

8.
Curr Opin Anaesthesiol ; 36(6): 676-682, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-37767926

ABSTRACT

PURPOSE OF REVIEW: This study indicates that there are differences between hospitals in detection, as well as in adequate management of postsurgical complications, a phenomenon that is described as 'failure-to-rescue'.In this review, recent initiatives to reduce failure-to-rescue in the perioperative period are described. RECENT FINDINGS: Use of cognitive aids, emergency manuals, family participation as well as remote monitoring systems are measures to reduce failure-to-rescue situations. Postoperative visit of an anaesthesiologist on the ward was not shown to improve outcome, but there is still room for improvement of postoperative care. SUMMARY: Improving the complete emergency chain, including monitoring, recognition and response in the afferent limb, as well as diagnostic and treatment in the efferent limb, should lead to reduced failure-to-rescue situations in the perioperative period.


Subject(s)
Hospitals , Postoperative Complications , Humans , Postoperative Complications/diagnosis , Postoperative Complications/prevention & control , Postoperative Care , Perioperative Period , Monitoring, Physiologic
9.
J Clin Med ; 12(16)2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37629237

ABSTRACT

BACKGROUND: The appropriate management of a "difficult airway" remains a challenge for novices and experienced anaesthetists. With the current available airway technologies, e.g., video laryngoscopy, flexible bronchoscopy (fibreoptic intubation (FOI)) for endotracheal intubation is decreasing, likely diminishing caregiver skills. We investigated whether bronchoscopy simulator training improved FOI skills. METHODS: 72 volunteers, consisting of anaesthetists, anaesthesia residents, and nurses, performed six exercises on a bronchoscopy simulator. At baseline and after 12 months, the six exercises included one serious game (to train agility), two basic airways, and three difficult airways. After a baseline assessment, subjects were randomly allocated to the intervention group (with) or control group without bronchoscopy simulator training every six weeks for 10 min using a preloaded serious game. The primary outcome was the difference in the time to reach the carina after 12 months, as measured objectively by the simulator. The level of stress and FOI confidence after 12 months were secondary outcomes. RESULTS: The control and intervention groups had a similar time to reach the carina in difficult airway cases and the reported stress levels, at baseline and 12 months, showed no difference. In contrast, the intervention group's self-reported confidence in FOI skills improved more. CONCLUSIONS: Although participants rated higher in confidence, practicing FOI skills on an airway simulator with an agility game did not increase their performance in simulated challenging airway instances.

10.
Cells ; 12(10)2023 05 20.
Article in English | MEDLINE | ID: mdl-37408266

ABSTRACT

Pharmacological conditioning aims to protect the heart from myocardial ischemia-reperfusion injury (IRI). Despite extensive research in this area, today, a significant gap remains between experimental findings and clinical practice. This review provides an update on recent developments in pharmacological conditioning in the experimental setting and summarizes the clinical evidence of these cardioprotective strategies in the perioperative setting. We start describing the crucial cellular processes during ischemia and reperfusion that drive acute IRI through changes in critical compounds (∆GATP, Na+, Ca2+, pH, glycogen, succinate, glucose-6-phosphate, mitoHKII, acylcarnitines, BH4, and NAD+). These compounds all precipitate common end-effector mechanisms of IRI, such as reactive oxygen species (ROS) generation, Ca2+ overload, and mitochondrial permeability transition pore opening (mPTP). We further discuss novel promising interventions targeting these processes, with emphasis on cardiomyocytes and the endothelium. The limited translatability from basic research to clinical practice is likely due to the lack of comorbidities, comedications, and peri-operative treatments in preclinical animal models, employing only monotherapy/monointervention, and the use of no-flow (always in preclinical models) versus low-flow ischemia (often in humans). Future research should focus on improved matching between preclinical models and clinical reality, and on aligning multitarget therapy with optimized dosing and timing towards the human condition.


Subject(s)
Mitochondrial Membrane Transport Proteins , Myocardial Reperfusion Injury , Animals , Humans , Mitochondrial Permeability Transition Pore , Myocytes, Cardiac , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/prevention & control , Ischemia
11.
Crit Care ; 27(1): 282, 2023 07 12.
Article in English | MEDLINE | ID: mdl-37434172

ABSTRACT

BACKGROUND: Iatrogenic cerebral arterial gas embolism (CAGE) caused by invasive medical procedures may be treated with hyperbaric oxygen therapy (HBOT). Previous studies suggested that initiation of HBOT within 6-8 h is associated with higher probability of favorable outcome, when compared to time-to-HBOT beyond 8 h. We performed a group level and individual patient level meta-analysis of observational studies, to evaluate the relationship between time-to-HBOT and outcome after iatrogenic CAGE. METHODS: We systematically searched for studies reporting on time-to-HBOT and outcome in patients with iatrogenic CAGE. On group level, we meta-analyzed the differences between median time-to-HBOT in patients with favorable versus unfavorable outcome. On individual patient level, we analyzed the relationship between time-to-HBOT and probability of favorable outcome in a generalized linear mixed effects model. RESULTS: Group level meta-analysis (ten studies, 263 patients) shows that patients with favorable outcome were treated with HBOT 2.4 h (95% CI 0.6-9.7) earlier than patients with unfavorable outcome. The generalized linear mixed effects model (eight studies, 126 patients) shows a significant relationship between time-to-HBOT and probability of favorable outcome (p = 0.013) that remains significant after correcting for severity of manifestations (p = 0.041). Probability of favorable outcome decreases from approximately 65% when HBOT is started immediately, to 30% when HBOT is delayed for 15 h. CONCLUSIONS: Increased time-to-HBOT is associated with decreased probability of favorable outcome in iatrogenic CAGE. This suggests that early initiation of HBOT in iatrogenic CAGE is of vital importance.


Subject(s)
Embolism, Air , Hyperbaric Oxygenation , Humans , Cognition , Embolism, Air/etiology , Embolism, Air/therapy , Hyperbaric Oxygenation/adverse effects , Iatrogenic Disease , Linear Models , Observational Studies as Topic
12.
J Cardiothorac Vasc Anesth ; 37(10): 1951-1958, 2023 10.
Article in English | MEDLINE | ID: mdl-37438180

ABSTRACT

OBJECTIVES: To estimate the current practice in the perioperative management of patients undergoing cardiac surgery due to infective endocarditis. DESIGN: A prospective, open, 24-item, web-based cross-sectional survey. SETTING: Online survey endorsed by the European Association of Cardiothoracic Anesthesiology and Intensive Care (EACTAIC). PARTICIPANTS: Members of the EACTAIC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 156 responses from 44 countries were received, with a completion rate of 99%. The response rate was 16.6%. Most respondents (76%) practiced cardiac anesthesia in European hospitals, and most respondents stated that a multidisciplinary endocarditis team was not established at their center, that cardiac anesthesiologists appeared to be involved infrequently in those teams (36%), and that they were not involved in decision-making on indication and timing of surgery (88%). In contrast, the cardiac anesthesiologist performed intraoperative antibiotic therapy (62%) and intraoperative transesophageal echocardiography (90%). Furthermore, there was a relative heterogeneity concerning perioperative monitoring, as well as for coagulation and transfusion management. CONCLUSIONS: This international survey evaluated current practice among cardiac anesthesiologists in the perioperative management of patients with infective endocarditis and the anesthesiologist's role in multidisciplinary decision-making. Heterogeneity in treatment approaches was identified, indicating relevant knowledge gaps that should encourage further clinical research to optimize treatment and postoperative outcomes in this specific population.


Subject(s)
Cardiac Surgical Procedures , Endocarditis , Humans , Cross-Sectional Studies , Prospective Studies , Surveys and Questionnaires , Endocarditis/surgery
13.
J Clin Med ; 12(9)2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37176605

ABSTRACT

BACKGROUND: The advantages of PCEA over CEA have been demonstrated in obstetric patients. Whether a similar benefit applies to surgical patients is unclear. METHODS: Embase, PubMed, and Cochrane Library were searched, enabling a systematic review of studies comparing PCEA and CEA in adult surgical patients (PROSPERO: CRD42018106644). The study quality was assessed using the Cochrane risk-of-bias tool (RoB2). The primary outcome was pain scores on postoperative day one (POD1). Secondary outcomes were 24 or 48 h epidural or intravenous total analgesic dose, systemic analgesics, manual top-ups, side effects, and patient satisfaction. RESULTS: Six randomized controlled trials with high heterogeneity of study characteristics were identified with a moderate risk of bias. Two studies showed significantly reduced resting pain scores on POD1 in PCEA compared with CEA patients (36-44%, p < 0.05). Four studies found comparable pain scores between these groups. PCEA use reduced epidural medication (28% to 40% reduction, p < 0.01) in four studies. One study found a 23% reduction (p < 0.001) of top-ups in PCEA; intravenous morphine use by PCEA patients was reduced (0.16 vs. 3.45 mg per patient, p < 0.05) in one study. PCEA patients were more satisfied with analgesia (p < 0.001) in two studies. Nausea and vomiting were reduced in PCEA (p = 0.01). CONCLUSIONS: Regarding the reduction in pain scores, the effects of PCEA were not significant or clinically not relevant. However, regarding the amount of epidural drug use, the amount of required rescue systemic analgesics, patient satisfaction, and the number of required top-ups, PCEA had advantages over CEA in surgical patients.

14.
PLoS One ; 18(4): e0284329, 2023.
Article in English | MEDLINE | ID: mdl-37053130

ABSTRACT

BACKGROUND: The coagulation system is crucial in the pathogenesis of infective endocarditis and undergoes significant changes during course of the disease. However, little is known about the implications of those changes in the perioperative period. Aim of the present study was to delineate the specific coagulation patterns and their clinical consequence in patients undergoing cardiac surgery due to infective endocarditis. METHODS: In this single-centre, exploratory, prospective observational study, we investigated the incidence and degree of coagulopathy in patients with (n = 31) and without infective endocarditis (n = 39) undergoing cardiac valve surgery. The primary outcome was the differences between these two groups in rotational thromboelastometry (ROTEM) results before, during and after surgery. The secondary outcomes were the differences between the groups in heparin sensitivity, bleeding complications, and transfusion requirements. RESULTS: Most ROTEM parameters in EXTEM, INTEM and FIBTEM assays were significantly altered in patients with infective endocarditis. Clotting time in the EXTEM assay was significantly prolonged in the endocarditis group at all time-points, while all clot firmness parameters (A5, A10 and MCF) were significantly increased. The heparin sensitivity index was significantly lower in the endocarditis group (median index 0.99 vs 1.17s. IU-1.kg-1, p = .008), indicating increased heparin resistance. Patients with infective endocarditis had more bleeding complications as assessed by the universal definition of perioperative bleeding score (OR 3.0, p = .018), and more patients with endocarditis underwent early re-exploration (p = .018). CONCLUSIONS: The findings of this exploratory investigation show significantly altered coagulation profiles in patients with infective endocarditis, with concomitant hyper- and hypocoagulability. Furthermore, the incidence of bleeding complications and transfusion requirements were increased in patients with endocarditis. These results show the potential of ROTEM to detect coagulation abnormalities in patients with infective endocarditis. Existing point-of-care coagulation testing guided algorithms for optimizing perioperative coagulation management possibly need to be adjusted for these high-risk patients undergoing cardiac surgery.


Subject(s)
Blood Coagulation Disorders , Cardiac Surgical Procedures , Endocarditis, Bacterial , Endocarditis , Humans , Thrombelastography/methods , Blood Coagulation Tests , Hemorrhage/complications , Cardiac Surgical Procedures/adverse effects , Heparin , Endocarditis/complications , Endocarditis/surgery
15.
Simul Healthc ; 18(6): 367-374, 2023 Dec 01.
Article in English | MEDLINE | ID: mdl-36877689

ABSTRACT

BACKGROUND: Nontechnical skills in cardiac surgery are vital in ensuring patient safety in the operating room (OR). To train these skills in a simulation-based scenario, a collection of commonly accepted crisis scenarios is needed to serve as a framework for a simulation-based training program. OBJECTIVE: The objective of this study was to identify and reach consensus on a collection of relevant crisis scenarios in cardiac surgery suitable for simulation-based team training focusing on nontechnical skills. METHODS: Using the Delphi method, a national assessment was performed among cardiac surgeons, cardiac anesthesiologists, clinical perfusionists, and cardiac OR nurses in the Netherlands. In the first Delphi round, potential crisis scenarios for simulation-based team training in cardiac surgery were identified. In the second round, the identified scenarios were rated using a 5-point Likert scale. Finally, based on consensus (two-thirds majority), scenarios were prioritized and explored for feasibility. RESULTS: One hundred fourteen experts participated in the study (26 cardiac anesthesiologists, 24 cardiac surgeons, 25 clinical perfusionists, and 39 OR nurses), representing all 16 cardiac surgical centers in the Netherlands. In the first round, 237 scenarios were identified. After eliminating duplicates and grouping similar scenarios, 44 scenarios were scored in round 2, which finally resulted in 13 relevant crisis scenarios with an expert consensus higher than 67%. CONCLUSIONS: Thirteen crisis scenarios relevant to simulation-based team training were identified by an expert panel consisting of all members of the cardiac surgical team. Further research is needed to evaluate the educational value of the respective scenarios.


Subject(s)
Simulation Training , Surgeons , Humans , Anesthesiologists , Operating Rooms , Clinical Competence , Patient Care Team
17.
Biomed Pharmacother ; 159: 114228, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36623448

ABSTRACT

BACKGROUND: Canagliflozin (CANA) shows anti-inflammatory and anti-oxidative effects on endothelial cells (ECs). In diabetes mellitus (DM), excessive reactive oxygen species (ROS) generation, increased intracellular calcium (Ca2+) and enhanced extracellular signal regulated kinase (ERK) 1/2 phosphorylation are crucial precursors for inflammasome activation. We hypothesized that: (1) CANA prevents the TNF-α triggered ROS generation in ECs from diabetic donors and in turn suppresses the inflammasome activation; and (2) the anti-inflammatory effect of CANA is mediated via intracellular Ca2+ and ERK1/2. METHODS: Human coronary artery endothelial cells from donors with DM (D-HCAECs) were pre-incubated with either CANA or vehicle for 2 h before exposure to 50 ng/ml TNF-α for 2-48 h. NAC was applied to scavenge ROS, BAPTA-AM to chelate intracellular Ca2+, and PD 98059 to inhibit the activation of ERK1/2. Live cell imaging was performed at 6 h to measure ROS and intracellular Ca2+. At 48 h, ELISA and infra-red western blot were applied to detect IL-1ß, NLRP3, pro-caspase-1 and ASC. RESULTS: 10 µM CANA significantly reduced TNF-α related ROS generation, IL-1ß production and NLRP3 expression (P all <0.05), but NAC did not alter the inflammasome activation (P > 0.05). CANA and BAPTA both prevented intracellular Ca2+ increase in cells exposed to TNF-α (P both <0.05). Moreover, BAPTA and PD 98059 significantly reduced the TNF-α triggered IL-1ß production as well as NLRP3 and pro-caspase-1 expression (P all <0.05). CONCLUSION: CANA suppresses inflammasome activation by inhibition of (1) intracellular Ca2+ and (2) ERK1/2 phosphorylation, but not by ROS reduction.


Subject(s)
Diabetes Mellitus , Inflammasomes , Humans , Inflammasomes/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Canagliflozin/pharmacology , Calcium , Endothelial Cells/metabolism , Caspase 1/metabolism , Reactive Oxygen Species/metabolism , Tumor Necrosis Factor-alpha , Signal Transduction , Interleukin-1beta/metabolism
18.
J Clin Anesth ; 84: 111012, 2023 02.
Article in English | MEDLINE | ID: mdl-36427486

ABSTRACT

Diabetes mellitus is often treated as a uniform disease in the perioperative period. Type 2 diabetes is most commonly encountered, and only a minority of surgical patients have been diagnosed with another type of diabetes. Patients with a specific type of diabetes can be particularly prone to perioperative glycaemic dysregulation. In addition, certain type-related features and pitfalls should be taken into account in the operating theatre. In this narrative review, we discuss characteristics of types of diabetes other than type 2 diabetes relevant to the anaesthetist, based on available literature and data from our clinic.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Diabetes Mellitus, Type 2/complications , Anesthetists , Anesthesiologists , Perioperative Period , Blood Glucose
19.
Gerontology ; 69(2): 189-200, 2023.
Article in English | MEDLINE | ID: mdl-35660665

ABSTRACT

INTRODUCTION: Delayed neurocognitive recovery (DNR; neurocognitive disorder up to 30 days postoperative) and postoperative neurocognitive disorders (POCD; neurocognitive disorder 1-12 months postoperative) occur frequently after surgery, with diabetes mellitus (DM) suggested to contribute to this. This was a single-center prospective cohort study. The main aim of this study was to investigate the role of DM and preoperative hemoglobin A1c (HbA1c) in the development of POCDs after noncardiac surgery. METHODS: Older adult patients ≥65 years of age scheduled for elective surgery were recruited. The Modified Telephone Interview for Cognitive Status questionnaire (TICS-M), a test of global cognitive functioning, was administered to determine cognition. Preoperative, 30-day postoperative, and 6-month postoperative cognition were compared for patients with and without DM. Cognitive decline was subdivided into mild (1 to 2 standard deviations below controls) and major (≥2 standard deviations below controls) DNR or POCD. Preoperative HbA1c levels were correlated with TICS-M scores. RESULTS: We analyzed 102 patients [median (IQR [range]) age 72.0 (5 [68-74])]), who were divided into patients with DM (80 patients [78%]) and patients without DM (22 patients [22%]). Baseline cognitive function was similar for both groups. Repeated measures ANOVA showed that mean DM patient TICS-M scores decreased 30 days postoperative (F(2, 200) = 4.0, p = 0.02), with subsequent recovery 6-month postoperative, compared to stable TICS-M scores in non-DM patients. There were significantly more DM patients with DNR than non-DM patients (n = 11 [50%] vs. n = 14 [17.5%]; p = 0.031). There were no between-group differences in mild or major POCD. Higher preoperative HbA1c levels were significantly correlated with decreased 30-day Δcognition scores (F(1, 54) = 9.4, p = 0.003) with an R2 of 0.149 (ß -0.45, 95% confidence interval: -0.735 to -0.154). CONCLUSIONS: Older adult patients with DM undergoing surgery have an increased risk of DNR compared to older adult non-DM patients, but no increased risk of POCD. In DM patients, higher preoperative HbA1c levels were associated with an increased risk of DNR.


Subject(s)
Cognitive Dysfunction , Diabetes Mellitus , Humans , Aged , Prospective Studies , Glycated Hemoglobin , Neuropsychological Tests , Cognitive Dysfunction/etiology , Postoperative Complications/etiology
20.
J Neurosurg Anesthesiol ; 35(1): 65-73, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-34387283

ABSTRACT

BACKGROUND: Cerebral autoregulation (CA) continuously adjusts cerebrovascular resistance to maintain cerebral blood flow (CBF) constant despite changes in blood pressure. Also, CBF is proportional to changes in arterial carbon dioxide (CO 2 ) (cerebrovascular CO 2 reactivity). Hypercapnia elicits cerebral vasodilation that attenuates CA efficacy, while hypocapnia produces cerebral vasoconstriction that enhances CA efficacy. In this study, we quantified the influence of sevoflurane anesthesia on CO 2 reactivity and the CA-CO 2 relationship. METHODS: We studied patients with type 2 diabetes mellitus (DM), prone to cerebrovascular disease, and compared them to control subjects. In 33 patients (19 DM, 14 control), end-tidal CO 2 , blood pressure, and CBF velocity were monitored awake and during sevoflurane-based anesthesia. CA, calculated with transfer function analysis assessing phase lead (degrees) between low-frequency oscillations in CBF velocity and mean arterial blood pressure, was quantified during hypocapnia, normocapnia, and hypercapnia. RESULTS: In both control and DM patients, awake CO 2 reactivity was smaller (2.8%/mm Hg CO 2 ) than during sevoflurane anesthesia (3.9%/mm Hg; P <0.005). Hyperventilation increased CA efficacy more (3 deg./mm Hg CO 2 ) in controls than in DM patients (1.8 deg./mm Hg CO 2 ; P <0.001) in both awake and sevoflurane-anesthetized states. CONCLUSIONS: The CA-CO 2 relationship is impaired in awake patients with type 2 DM. Sevoflurane-based anesthesia does not further impair this relationship. In patients with DM, hypocapnia induces cerebral vasoconstriction, but CA efficacy does not improve as observed in healthy subjects.


Subject(s)
Anesthesia , Anesthetics, Inhalation , Diabetes Mellitus, Type 2 , Humans , Sevoflurane/pharmacology , Carbon Dioxide , Hypercapnia , Hypocapnia , Anesthetics, Inhalation/pharmacology , Homeostasis/physiology
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