Cerebral Glucose Metabolism following TBI: Changes in Plasma Glucose, Glucose Transport and Alternative Pathways of Glycolysis-A Translational Narrative Review.

Traumatic brain injury (TBI) is a major public health concern with significant consequences across various domains. Following the primary event, secondary injuries compound the outcome after TBI, with disrupted glucose metabolism emerging as a relevant factor. This narrative review summarises the existing literature on post-TBI alterations in glucose metabolism. After TBI, the brain undergoes dynamic changes in brain glucose transport, including alterations in glucose transporters and kinetics, and disruptions in the blood-brain barrier (BBB). In addition, cerebral glucose metabolism transitions from a phase of hyperglycolysis to hypometabolism, with upregulation of alternative pathways of glycolysis. Future research should further explore optimal, and possibly personalised, glycaemic control targets in TBI patients, with GLP-1 analogues as promising therapeutic candidates. Furthermore, a more fundamental understanding of alterations in the activation of various pathways, such as the polyol and lactate pathway, could hold the key to improving outcomes following TBI.

Preoperative Glycosylated Haemoglobin Screening to Identify Older Adult Patients with Undiagnosed Diabetes Mellitus-A Retrospective Cohort Study.

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.

Perioperative management of long-acting glucagon-like peptide-1 (GLP-1) receptor agonists: concerns for delayed gastric emptying and pulmonary aspiration.

Prescriptions and use of glucagon-like peptide-1 (GLP-1) receptor agonists are increasing dramatically, as indications are expanding from the treatment of diabetes mellitus to weight loss for people with obesity. As GLP-1 receptor agonists delay gastric emptying, perioperative healthcare practitioners could be concerned about an increased risk for pulmonary aspiration during general anaesthesia. We summarise relevant medical literature and provide evidence-based recommendations for perioperative care for people taking GLP-1 receptor agonists. GLP-1 receptor agonists delay gastric emptying; however, ongoing treatment attenuates this effect. The risk of aspiration during general anaesthesia is unknown. However, we advise caution in patients who recently commenced on GLP-1 receptor agonists. After over 12 weeks of treatment, standard fasting times likely suffice to manage the risk of pulmonary aspiration for most otherwise low-risk patients.

The Effect of Preoperative Disability, Cognitive Impairment, Frailty and Opioid Use on Acute Postoperative Pain in Older Patients Undergoing Surgery A Prospective Cohort Study.

Globally, life expectancy is increasing, leading to more surgeries being performed in older patients. Postoperative pain is associated with complications after surgery. The aim of this study is to explore potential age-related risk factors for acute postoperative pain in older patients undergoing surgery. This was a prospective, single-center study. Patients ≥65 years, with and without disability, as defined by the WHO Disability Assessment Schedule 2.0, undergoing elective surgery, were compared. Primary outcome was the postoperative pain (ie, numeric rating scale (NRS) score) on the first postoperative day. Secondary outcomes were postoperative pain and pain trajectories in patients with and without mild cognitive impairment (MCI), frailty, preoperative opioid use, and new-onset disability after surgery. Between February 2019 and July 2020, 155 patients were enrolled. On the first day after surgery, postoperative pain did not differ between patients with and without disability. NRS scores differed between patients with-, and without MCI on the first (P = .01), and second postoperative day (P < .01). Patients who used opioids before surgery reported higher median NRS score on the first (P < .001) and second (P < .01) postoperative day. Out of a total of 1816 NRS scores, 2 pain clusters were identified. Acute postoperative pain did not differ between patients with or without preoperative disability and frailty in older patients undergoing surgery. Reduced postoperative pain in older patients with MCI warrants further investigation. The PIANO study (Comparison of Postoperative NeurocognitiveFunction in Older Adult Patients with and without Diabetes Mellitus) was registered with www.clinicaltrialregister.nl (search term: Which can predict memory problems after surgery better; blood sugar levels or memory before surgery?). PERSPECTIVE: This study explored risk factors for acute postoperative pain in older patients. No differences in postoperative pain were observed in patients with or without preexistent disability or frailty, however, patients with mild cognitive impairment experienced reduced pain. We suggest to simplify pain assessment in this group and take functional recovery into account.

Moral distress and positive experiences of ICU staff during the COVID-19 pandemic: lessons learned.

BACKGROUND: The COVID-19 pandemic causes moral challenges and moral distress for healthcare professionals and, due to an increased work load, reduces time and opportunities for clinical ethics support services. Nevertheless, healthcare professionals could also identify essential elements to maintain or change in the future, as moral distress and moral challenges can indicate opportunities to strengthen moral resilience of healthcare professionals and organisations. This study describes 1) the experienced moral distress, challenges and ethical climate concerning end-of-life care of Intensive Care Unit staff during the first wave of the COVID-19 pandemic and 2) their positive experiences and lessons learned, which function as directions for future forms of ethics support. METHODS: A cross-sectional survey combining quantitative and qualitative elements was sent to all healthcare professionals who worked at the Intensive Care Unit of the Amsterdam UMC - Location AMC during the first wave of the COVID-19 pandemic. The survey consisted of 36 items about moral distress (concerning quality of care and emotional stress), team cooperation, ethical climate and (ways of dealing with) end-of-life decisions, and two open questions about positive experiences and suggestions for work improvement. RESULTS: All 178 respondents (response rate: 25-32%) showed signs of moral distress, and experienced moral dilemmas in end-of-life decisions, whereas they experienced a relatively positive ethical climate. Nurses scored significantly higher than physicians on most items. Positive experiences were mostly related to 'team cooperation', 'team solidarity' and 'work ethic'. Lessons learned were mostly related to 'quality of care' and 'professional qualities'. CONCLUSIONS: Despite the crisis, positive experiences related to ethical climate, team members and overall work ethic were reported by Intensive Care Unit staff and quality and organisation of care lessons were learned. Ethics support services can be tailored to reflect on morally challenging situations, restore moral resilience, create space for self-care and strengthen team spirit. This can improve healthcare professionals' dealing of inherent moral challenges and moral distress in order to strengthen both individual and organisational moral resilience. TRIAL REGISTRATION: The trial was registered on The Netherlands Trial Register, number NL9177.

Comparison of Postoperative Neurocognitive Function in Older Adult Patients with and without Diabetes Mellitus.

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.

The Options for Neuraxial Drug Administration.

Neuraxial drug administration, i.e., the injection of drugs into the epidural or intrathecal space to produce anesthesia or analgesia, is a technique developed more than 120 years ago. Today, it still is widely used in daily practice in anesthesiology and in acute and chronic pain therapy. A multitude of different drugs have been introduced for neuraxial injection, only a part of which have obtained official approval for that indication. A broad understanding of the pharmacology of those agents is essential to the clinician to utilize them in a safe and efficient manner. In the present narrative review, we summarize current knowledge on neuraxial anatomy relevant to clinical practice, including pediatric anatomy. Then, we delineate the general pharmacology of neuraxial drug administration, with particular attention to specific aspects of epidural and intrathecal pharmacokinetics and pharmacodynamics. Furthermore, we describe the most common clinical indications for neuraxial drug administration, including the perioperative setting, obstetrics, and chronic pain. Then, we discuss possible neurotoxic effects of neuraxial drugs, and moreover, we detail the specific properties of the most commonly used neuraxial drugs that are relevant to clinicians who employ epidural or intrathecal drug administration, in order to ensure adequate treatment and patient safety in these techniques. Finally, we give a brief overview on new developments in neuraxial drug therapy.

Elevated cerebrospinal fluid glucose levels and diabetes mellitus are associated with activation of the neurotoxic polyol pathway.

AIMS/HYPOTHESIS: During hyperglycaemia, some glucose bypasses glycolysis and is metabolised via the potentially neurotoxic polyol pathway, in which glucose is metabolised to sorbitol and fructose. Increased polyol concentrations have been demonstrated in the cerebrospinal fluid (CSF) of neurological patients with and without diabetes mellitus. However, polyol levels in patients without evident neurological abnormalities have not been investigated so far. The aim of this study was to determine CSF polyol concentrations in patients without major neurological disease with normal or elevated CSF glucose concentrations. METHODS: This observational cohort study used CSF and plasma analyses, as well as clinical data, from 30 participants of the Anaesthetic Biobank of Cerebrospinal Fluid study. Biomaterial was collected from adult patients scheduled for elective surgery under spinal anaesthesia. CSF polyol concentrations were measured by GC/flame ionisation detector in ten patients with normal CSF glucose levels (group 1), ten patients with elevated CSF glucose levels (group 2) and ten patients with elevated CSF glucose levels and type 2 diabetes (group 3). We compared the concentrations of plasma glucose, CSF glucose, sorbitol and fructose, and CSF polyol/glucose ratios between the three groups, and determined the correlation between plasma glucose levels and CSF glucose, sorbitol and fructose levels. RESULTS: Groups 2 and 3 had significantly higher CSF fructose levels compared with group 1 (p=0.036 and p<0.001, respectively). Group 3 showed significant differences compared with groups 1 and 2 for CSF sorbitol (p<0.001 and 0.036, respectively). Moreover, patients with diabetes had a significantly higher CSF sorbitol/glucose ratio compared with patients without diabetes. There was a strong positive correlation between plasma glucose and CSF glucose, sorbitol and fructose. Finally, age, sex, CSF/plasma albumin ratio and preoperative cognitive function scores were significantly correlated with plasma glucose and CSF glucose, sorbitol and fructose levels. CONCLUSIONS/INTERPRETATION: Hyperglycaemia causes a proportional increase in polyol concentrations in CSF of patients without major neurological disease. Furthermore, this study provides the first indication of upregulation of the cerebral polyol pathway in patients with diabetes without evident neurological abnormalities.

The role of intraoperative hypotension on the development of postoperative cognitive dysfunction: a systematic review.

STUDY OBJECTIVE: To clarify whether intraoperative hypotension contributes to the development of postoperative cognitive dysfunction. DESIGN: A systematic review of prospective studies reporting on intraoperative hypotension and postoperative cognitive dysfunction in elective, non-cognitive impaired, adult surgical patients. PubMed, EMBASE and the Cochrane Library were searched up to the 1st of January 2021. SETTING: Studies had to use a clear definition of hypotension, although differing definitions were accepted. Neurocognitive tests to determine postoperative cognitive dysfunction had to be done pre- and postoperatively, with a minimum follow-up of seven days postoperatively. MEASUREMENTS: Risk of bias was assessed using the Cochrane Risk of Bias Tool 2.0 for randomized controlled trials and the Newcastle-Ottawa Scale for cohort studies. MAIN RESULTS: Out of 941 studies screened, five randomized controlled trials and four cohort studies were included for qualitative analysis. Extensive methodological differences between studies were present hindering proper quantitive analysis. No studies reported statistically significant differences in incidence of postoperative cognitive dysfunction in hypo- compared to normotensive patients. Five studies reported exact incidences of postoperative cognitive dysfunction. CONCLUSIONS: This systematic review showed no conclusive association between intraoperative hypotension and the development of postoperative cognitive dysfunction. Given the vast methodological differences of the included studies, the role of intraoperative hypotension in the development of postoperative cognitive dysfunction remains uncertain. Future research into the association between intraoperative hypotension and postoperative cognitive dysfunction should be conducted in a standardized manner.

Registration of attentional function as a predictor of incident delirium (the RAPID study).

INTRODUCTION: Older adults undergoing elective surgery have a high risk of developing postoperative delirium (POD). Validated models predicting POD are scarce. This study investigated whether preoperative impairment of attentional function predicts POD in older adults without previously diagnosed cognitive impairment. METHODS: In this prospective cohort study we recruited patients aged ≥70 years preceding major elective surgery. Preoperatively a visual vigilance test was administered to determine intra-individual reaction-time variability. Postoperatively, presence of delirium was screened daily. RESULTS: We recruited 152 patients, 25 (16.4%) developed POD. Intra-individual reaction-time variability was not significantly different between patients with or without POD (0.18 ± 0.08 ms vs 0.22 ± 0.11 ms; P = 0.087). Receiver operating characteristic analyses indicated a poor accuracy for POD (area under the curve 0.609 ± 0.63). Except for surgery duration, no clinically significant between-group differences were found for secondary outcome parameters. DISCUSSION: Preoperative intra-individual reaction time variability does not predict the incidence of POD in older patients undergoing major elective surgery.