Physostigmine for prevention of postoperative delirium and long-term cognitive dysfunction in liver surgery: A double-blinded randomised controlled trial.

BACKGROUND: Anecdotally, cholinergic stimulation has been used to treat delirium and reduce cognitive dysfunction. OBJECTIVE: The aim of this investigation was to evaluate whether physostigmine reduced the incidence of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) in patients undergoing liver resection. DESIGN: This was a double-blind, randomised, placebo-controlled trial. Between 11 August 2009 and 3 March 2016, patients were recruited at the Charité - Universitätsmedizin Berlin in Germany. Follow-ups took place at 1 week (T1), 90 days (T2) and 365 days (T3) after surgery. SETTING: This single-centre study was conducted at an academic medical centre. PARTICIPANTS: In total, 261 participants aged at least 18 years scheduled for elective liver surgery were randomised. The protocol also included 45 non-surgical matched controls to provide normative data for POCD and neurocognitive deficit (NCD). INTERVENTION: Participants were allocated to receive either intravenous physostigmine, as a bolus of 0.02 mg kg-1 body weight followed by 0.01 mg kg-1 body weight per hour (n = 130), or placebo (n = 131), for 24 h after induction of anaesthesia. MAIN OUTCOMES AND MEASURES: Primary outcomes were POD, assessed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-4-TR) twice daily up to day 7 after surgery, and POCD assessed via the CANTAB neuropsychological test battery, and two paper pencil tests on the day before surgery, and on postoperative days 7, 90 and 365. RESULTS: In total, 261 patients were randomised, 130 to the physostigmine and 131 to the placebo group. The incidence of POD did not differ significantly between the physostigmine and placebo groups (20 versus 15%; P = 0.334). Preoperative cognitive impairment and POCD frequencies did not differ significantly between the physostigmine and placebo groups at any time. Lower mortality rates were found in the physostigmine group compared with placebo at 3 months [2% (95% confidence interval (CI), 0 to 4) versus 11% (95% CI, 6 to 16), P = 0.002], and 6 months [7% (95% CI, 3 to 12) versus 16% (95% CI, 10 to 23), P = 0.012] after surgery. CONCLUSION: Physostigmine had no effect on POD and POCD when applied after induction of anaesthesia up to 24 h. TRIAL REGISTRATION: DOI 10.1186/ISRCTN18978802, EudraCT 2008-007237-47, Ethics approval ZS EK 11 618/08 (15 January 2009).

The association between intraoperative hyperglycemia and cerebrovascular markers.

BACKGROUND AND PURPOSE: Hyperglycemia can lead to an increased rate of apoptosis of microglial cells and to damaged neurons. The relation between hyperglycemia and cerebrovascular markers on MRI is unknown. Our aim was to study the association between intraoperative hyperglycemia and cerebrovascular markers. METHODS: In this further analysis of a subgroup investigation of the BIOCOG study, 65 older non-demented patients (median 72 years) were studied who underwent elective surgery of ≥ 60 minutes. Intraoperative blood glucose maximum was determined retrospectively in each patient. In these patients, preoperatively and at 3 months follow-up a MRI scan was performed and white matter hyperintensity (WMH) volume and shape, infarcts, and perfusion parameters were determined. Multivariable logistic regression analyses were performed to determine associations between preoperative cerebrovascular markers and occurrence of intraoperative hyperglycemia. Linear regression analyses were performed to assess the relation between intraoperative hyperglycemia and pre- to postoperative changes in WMH volume. Associations between intraoperative hyperglycemia and postoperative WMH volume at 3 months follow-up were also assessed by linear regression analyses. RESULTS: Eighteen patients showed intraoperative hyperglycemia (glucose maximum ≥ 150 mg/dL). A preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia [convexity: OR 33.318 (95 % CI (1.002 - 1107.950); p = 0.050]. Other preoperative cerebrovascular markers were not related to the occurrence of intraoperative hyperglycemia. Intraoperative hyperglycemia showed no relation with pre- to postoperative changes in WMH volume nor with postoperative WMH volume at 3 months follow-up. CONCLUSIONS: We found that a preoperative more smooth shape of periventricular and confluent WMH was related to the occurrence of intraoperative hyperglycemia. These findings may suggest that a similar underlying mechanism leads to a certain pattern of vascular brain abnormalities and an increased risk of hyperglycemia.

Treatment and Mortality of Hemophagocytic Lymphohistiocytosis in Adult Critically Ill Patients: A Systematic Review With Pooled Analysis.

OBJECTIVES: Hemophagocytic lymphohistiocytosis is a cytokine release syndrome caused by uncontrolled immune activation resulting in multiple organ failure and death. In this systematic review, we aimed to analyze triggers, various treatment modalities, and mortality in critically ill adult hemophagocytic lymphohistiocytosis patients. DATA SOURCES: MEDLINE database (PubMed) at October 20, 2019. STUDY SELECTION: Studies and case series of patients greater than or equal to 18 years old, of whom at least one had to be diagnosed with hemophagocytic lymphohistiocytosis and admitted to an ICU. DATA EXTRACTION: Source data of studies and case series were summarized and analyzed on an individual basis. Multivariable logistic regression analysis was performed adjusting for age, sex, and trigger groups. Each single treatment agent was entered as a dichotomous variable to determine treatments associated with survival, regardless if given alone or in combination. DATA SYNTHESIS: In total, 661 patients from 65 studies and case series were included. Overall mortality was 57.8%. Infections were the most frequent trigger (49.9%), followed by malignancies (28.0%), autoimmune diseases (12.1%), unknown triggers (9.4%), and drugs (0.6%). Treatment with IV immunoglobulins was associated with improved survival (odds ratio, 0.548; 95% CI, 0.337-0.891; p = 0.015), while treatment with cyclosporine was associated with increased risk of death (odds ratio, 7.571; 95% CI, 3.702-15.483; p < 0.001). Considering different trigger groups separately, same results occurred only for infection-triggered hemophagocytic lymphohistiocytosis. No information was available on disease severity and other confounding factors. CONCLUSIONS: Mortality of hemophagocytic lymphohistiocytosis in the ICU is high. Most common triggers were infections. Results of survival analyses may be biased by treatment indication and disease severity. Future studies prospectively investigating treatment tailored to critically ill hemophagocytic lymphohistiocytosis patients are highly warranted.

Epidural Anesthesia in Liver Surgery-A Propensity Score-Matched Analysis.

OBJECTIVE: To assess the effects of epidural anesthesia (EA) on patients who underwent liver resection. DESIGN: Secondary analysis of a prospective randomized controlled trial. SETTING: This single-center study was conducted at an academic medical center. METHODS: A subset of 110 1:1 propensity score-matched patients who underwent liver resection with and without EA were analyzed. Outcome measures were pain intensity ≥5 on a numeric rating scale (NRS) at rest and during movement on postoperative days 1-5, analyzed with logistic mixed-effects models, and postoperative complications according to the Clavien-Dindo classification, length of hospital stay (LOS), and one-year survival. One-year survival in the matched cohorts was compared using a frailty model. RESULTS: EA patients were less likely to experience NRS ≥5 at rest (odds ratio = 0.06, 95% confidence interval [CI] = 0.01 to 0.28, P < 0.001). These findings were independent of age, sex, Charlson comorbidity index, baseline NRS, and surgical approach (open vs laparoscopic). The number and severity of postoperative complications and LOS were comparable between groups (P = 0.258, P > 0.999, and P = 0.467, respectively). Reduced mortality rates were seen in the EA group one year after surgery (9.1% vs 30.9%, hazard ratio = 0.32, 95% CI = 0.11 to 0.90, P = 0.031). No EA-related adverse events occurred. Earlier recovery of bowel function was seen in EA patients. CONCLUSIONS: Patients with EA had better postoperative pain control and required fewer systemic opioids. Postoperative complications and LOS did not differ, although one-year survival was significantly improved in patients with EA. EA applied in liver surgery was effective and safe.

Hemophagocytic lymphohistiocytosis in critically ill patients: diagnostic reliability of HLH-2004 criteria and HScore.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare though often fatal hyperinflammatory syndrome mimicking sepsis in the critically ill. Diagnosis relies on the HLH-2004 criteria and HScore, both of which have been developed in pediatric or adult non-critically ill patients, respectively. Therefore, we aimed to determine the sensitivity and specificity of HLH-2004 criteria and HScore in a cohort of adult critically ill patients. METHODS: In this further analysis of a retrospective observational study, patients ≥ 18 years admitted to at least one adult ICU at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with hyperferritinemia of ≥ 500 µg/L were included. Patients' charts were reviewed for clinically diagnosed or suspected HLH. Receiver operating characteristics (ROC) analysis was performed to determine prediction accuracy. RESULTS: In total, 2623 patients with hyperferritinemia were included, of whom 40 patients had HLH. We found the best prediction accuracy of HLH diagnosis for a cutoff of 4 fulfilled HLH-2004 criteria (95.0% sensitivity and 93.6% specificity) and HScore cutoff of 168 (100% sensitivity and 94.1% specificity). By adjusting HLH-2004 criteria cutoffs of both hyperferritinemia to 3000 µg/L and fever to 38.2 °C, sensitivity and specificity increased to 97.5% and 96.1%, respectively. Both a higher number of fulfilled HLH-2004 criteria [OR 1.513 (95% CI 1.372-1.667); p <  0.001] and a higher HScore [OR 1.011 (95% CI 1.009-1.013); p <  0.001] were significantly associated with in-hospital mortality. CONCLUSIONS: An HScore cutoff of 168 revealed a sensitivity of 100% and a specificity of 94.1%, thereby providing slightly superior diagnostic accuracy compared to HLH-2004 criteria. Both HLH-2004 criteria and HScore proved to be of good diagnostic accuracy and consequently might be used for HLH diagnosis in critically ill patients. CLINICAL TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

Hyperferritinemia in Critically Ill Patients.

OBJECTIVE: Hyperferritinemia is frequently seen in critically ill patients. A rather rare though life-threatening condition related to severely elevated ferritin is hemophagocytic lymphohistiocytosis. We analyze ferritin levels to differentiate hemophagocytic lymphohistiocytosis from other causes of hyperferritinemia in a mixed cohort of critically ill patients. DESIGN: Retrospective observational study. SETTING: Adult surgical, anesthesiologic, and medical ICUs of a university hospital. PATIENTS: Critical care patients (≥ 18 yr old) admitted to any of the adult ICUs at Charité - Universitätsmedizin Berlin between January 2006 and August 2018 with at least one ferritin value and hyperferritinemia (≥ 500 µg/L). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were categorized into hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other diagnoses. These were further categorized into 17 subgroups. Hemophagocytic lymphohistiocytosis diagnosis was based on Hemophagocytic Lymphohistiocytosis-2004 criteria and the HScore. Of 2,623 patients with hyperferritinemia, 40 were considered to have hemophagocytic lymphohistiocytosis (1.52%). Maximum ferritin levels were highest in hemophagocytic lymphohistiocytosis patients compared with all other disease groups (each p < 0.001). Sepsis and septic shock patients had higher maximum ferritin levels than patients with other diagnoses (each p < 0.001). A maximum ferritin value of 9,083 µg/L was at 92.5% sensitivity and 91.9% specificity for hemophagocytic lymphohistiocytosis (area under the curve, 0.963; 95% CI, 0.949-0.978). Of all subgroups with other diagnoses, maximum ferritin levels were highest in patients with varicella-zoster virus, hepatitis, or malaria (median, 1,935, 1,928, and 1,587 µg/L, respectively). Maximum ferritin levels were associated with increased in-hospital mortality (odds ratio, 1.518 per log µg/L [95% CI, 1.384-1.665 per log µg/L]; p < 0.001). CONCLUSIONS: This is the largest study of patients with ferritin available in a mixed ICU cohort. Ferritin levels in patients with hemophagocytic lymphohistiocytosis, sepsis, septic shock, and other conditions were distinctly different, with the highest ferritin levels observed in hemophagocytic lymphohistiocytosis patients. Maximum ferritin of 9,083 µg/L showed high sensitivity and specificity and, therefore, may contribute to improved diagnosis of hemophagocytic lymphohistiocytosis in ICU. The inclusion of ferritin into the sepsis laboratory panel is warranted.

Presurgical cognitive impairment is associated with postoperative delirium and postoperative cognitive dysfunction.

BACKGROUND: Presurgical cognitive impairment (PreCI) is frequently seen in older age, but the influence on postoperative delirium (POD) and postoperative cognitive dysfunction (POCD) remains unclear. The present study sought to determine the association between PreCI, POD and POCD with special focus to different PreCI domains. METHODS: We analyzed 934 patients with complete baseline neurocognitive assessment. PreCI was determined as cognitive performance of at least two standard deviation (SD) below the mean performance of non-surgical controls. POD was assessed according to the Diagnostic and Statistical Manual of Mental Disorders 4 (DSM-4). POCD at three months follow-up was calculated by the reliable change index (RCI). Associations between PreCI and POD or POCD were assessed using multivariable logistic regression models adjusted for age, sex, randomization, ASA status, type of anesthesia, and type of surgery. RESULTS: PreCI was significantly associated with POD [OR 1.936 (95%CI 1.119 to 3.348); P=0.015] and POCD [OR 3.091 (95%CI 1.287 to 7.426); P=0.012]. Patients with coincident PreCI and POD were significantly more likely to develop POCD [OR 6.131 (95%CI 1.476 to 22.364); P=0.007]. Differentiation between no PreCI, amnestic and non-amnestic PreCI revealed a sole influence of amnestic PreCI on POD and POCD. CONCLUSIONS: Patients ≥ 60 years with PreCI were more likely to develop POD and POCD, respectively. The odds for POCD were highest in patients with PreCI whom also suffered from POD. Amnestic rather than non-amnestic PreCI might play a key role in the development of POD and POCD. These results warrant further pathophysiological investigations and demand preventive strategies.

Hemophagocytic Lymphohistiocytosis in Critically Ill Patients.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH), an uncontrolled overactivation of the immune system, is well characterized in pediatric patients, yet, much less is known about this life-threatening condition in adult patients. As HLH is often complicated by organ failure, patients will require admission to the intensive care unit for organ support therapy. However, recognition of HLH patients in the intensive care unit (ICU) is challenged by the clinical overlap with sepsis. Here, we analyze HLH patients to better understand its clinical presentation, diagnosis, and treatment. METHODS: For the purpose of this retrospective observational study, we searched for suspected and diagnosed adult HLH of all patients admitted to at least one adult surgical, anesthesiological or medical ICU between January 2006 and August 2018 at the university hospital Charité - Universitätsmedizin Berlin. All cases were reviewed by two HLH experts, who confirmed or declined the diagnosis. RESULTS: Of 6,340 ICU patients with ferritin measurement, 40 suffered from HLH (0.63%). Of these, in-hospital mortality was 60.0% over all cases, which was highest in malignancy-associated HLH (71.4%). Infections were identified as most common triggers (42.5%). A variety of 19 different treatment strategies were applied. Non-survivors showed higher ferritin at diagnosis compared with survivors (P = 0.021), which was also seen in multivariable analyses. A minimum ferritin of 4083 µg/L after diagnosis was most predictive for 30-day mortality (AUC 0.888, 95% CI 0.771-1.000; sensitivity 93.8%, specificity 78.9%). CONCLUSIONS: Mortality in adult HLH patients in the ICU is high, particularly in malignancy-associated HLH. Infections are the most frequent HLH triggers in critically ill patients. At present, there is no standardized treatment for HLH in adult patients available. Assessment of ferritin is valuable for diagnosis, prognosis, and treatment monitoring. TRIAL REGISTRATION: The study was registered with www.ClinicalTrials.gov (NCT02854943) on August 1, 2016.

[Recommendations for the Detection and Specification of Perioperative Neurocognitive Disorders]. / Empfehlungen zur Erfassung und Beschreibung perioperativer kognitiver Störungen in Wissenschaft und Praxis.

Perioperative neurocognitive disorders (pNCD) are relevant to long term treatment outcome after elective surgery. The detection of pNCD is challenging and based on extended neuropsychological testing that often is not feasible due to economy driven time constraints during preoperative risk assessment. Only recently new recommendations for the nomenclature of cognitive change associated with anaesthesia and surgery facilitated the transition of the former research diagnosis postoperative cognitive dysfunction (POCD) as a clinical diagnosis based on DSM-5 criteria. In our article we provide an overview of the new recommended diagnostic criteria for pNCD based on the publication by the Nomenclature Consensus Working Group in November 2018. We discuss ideas for the implementation of clinical routine pNCD screening in patients aged 70 years or older with elective surgery and possible options for further support of patients screened positively and their families and care givers.

[Perioperative Neurocognitive Disorders - Postoperative Prevention Strategies]. / Wie können postoperativ ein Delir und eine neurokognitive Störung verhindert werden?

Postoperative delirium (POD) is a common and serious complication after surgery. It is associated with increased morbidity and mortality as well as neurocognitive disorder and associated loss of autonomy and increased need for care. As professionals, it is our duty to treat our patients in a holistic individual concept with the aim to reintegrate our patients into their home and social environment afterwards. In addition to preoperative and intraoperative interventions, postoperative prevention is of particular importance. This article focuses on non-pharmacological prevention strategies to avoid postoperative delirium and neurocognitive disorder in postoperative inpatient care. It is based on the "Evidence-based and consensus-based guideline on postoperative delirium". Thus, risk factors are addressed and non-pharmacological strategies are presented, which include reorientation, mobilization and nutritional support. Interprofessional cooperation plays just as important a role as the implementation of the listed preventive measures. Finally, the modified Hospital Elder Life Program is presented, which presents and applies preventive measures as a system-oriented and interdisciplinary concept, which "prevents functional decline and allows older adults to return home at the maximal level of independence". From our point of view, the training of a professional delirium team is a future-oriented complementary measure in the treatment concept of Perioperative Neurocognitive Disorders (PND), which finds its justification as an interface in the treatment of high-risk patients.

Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients (HEMICU): a prospective observational study protocol.

INTRODUCTION: Haemophagocytic lymphohistiocytosis (HLH) in adults is characterised by toxic immune activation and a sepsis-like syndrome, leading to high numbers of undiagnosed cases and mortality rates of up to 68%. Early diagnosis and specific immune suppressive treatment are mandatory to avoid fatal outcome, but the diagnostic criteria (HLH-2004) are adopted from paediatric HLH and have not been validated in adults. Experimental studies suggest biomarkers to sufficiently diagnose HLH. However, biomarkers for the diagnosis of adult HLH have not yet been investigated. METHODS AND ANALYSIS: The HEMICU (Diagnostic biomarkers for adult haemophagocytic lymphohistiocytosis in critically ill patients) study aims to estimate the incidence rate of adult HLH among suspected adult patients in intensive care units (ICUs). Screening for HLH will be performed in 16 ICUs of Charité - Universitätsmedizin Berlin. The inclusion criteria are bicytopaenia, hyperferritinaemia (≥500 µg/L), fever or when HLH is suspected by the clinician. Over a period of 2 years, we expect inclusion of about 100 patients with suspected HLH. HLH will be diagnosed if at least five of the HLH-2004 criteria are fulfilled, together with an expert review; all other included patients will serve as controls. Second, a panel of potential biomarker candidates will be explored. DNA, plasma and serum will be stored in a biobank. The primary endpoint of the study is the incidence rate of adult HLH among suspected adult patients during ICU stay. Out of a variety of measured biomarkers, this study furthermore aims to find highly potential biomarkers for the diagnosis of adult HLH in ICU. The results of this study will contribute to improved recognition and patient outcome of adult HLH in clinical routine. ETHICS AND DISSEMINATION: The institutional ethics committee approved this study on 1 August 2018 (Ethics Committee of Charité - Universitätsmedizin Berlin, EA4/006/18). The results of the study will be disseminated in an international peer-reviewed journal and presented at international conferences. TRIAL REGISTRATION NUMBER: NCT03510650.

Intraoperative hyperglycemia increases the incidence of postoperative delirium.

BACKGROUND: Hyperglycemia frequently occurs during major surgery and is associated with adverse postoperative outcomes. This study aimed to investigate the influence of intraoperative hyperglycemia on incidences of postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). METHODS: Eighty-seven patients aged ≥65 years undergoing elective surgery were included in this prospective observational subproject of the BioCog study. Blood glucose (BG) levels were measured every 20 minutes intraoperatively. Hyperglycemia was defined as BG levels ≥150 mg·dL-1. Patients were assessed for POD twice daily until postoperative day 7. The occurrence of POCD was determined three months after surgery. Multivariable logistic regression was used to identify associations between hyperglycemia and POD as well as POCD. Secondary endpoints comprised duration of hyperglycemia, maximum glucose level (Glucosemax) and differences between diabetic and non-diabetic patients. RESULTS: POD occurred in 41 (47.1%), POCD in five (15.2%) patients. In two separate multivariable logistic regression models, hyperglycemia was significantly associated with POD (OR 3.86 [CI 95% 1.13, 39.49], P=0.044) but not POCD (3.59 [NaN, NaN], P=0.157). Relative duration of hyperglycemia was higher in POD patients compared to patients without POD (20 [0; 71] % versus 0 [0; 55] %, P=0.075), whereas the maximum glucose levels during surgery were similar between the two groups. Considering only non-diabetic patients, relative duration of hyperglycemia (P=0.003) and Glucosemax (P=0.015) were significantly higher in patients with POD. CONCLUSIONS: Intraoperative hyperglycemia was independently associated with POD but not POCD. Relative duration of hyperglycemia appeared thereby to also play a role. Especially hyperglycemic non-diabetic patients might be at high risk for POD.

[Hemophagocytic lymphohistiocytosis in unspecific virus infection]. / Hämophagozytische Lymphohistiozytose bei unspezifischer Virusinfektion.

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome or macrophage activation syndrome within a pre-existing rheumatological disease, remains undiagnosed in over 70% of all cases in intensive care units (ICU) due to the sepsis-like clinical presentation. This report describes the case of a 30-year-old previously healthy male patient who was admitted to the normal infectiology ward of the Charité - Universitätsmedizin Berlin with unclear fever after a 3­month journey around Asian and South America. The patient was transferred to the ICU after 3 days because of respiratory failure. Due to the immediate diagnostics of HLH and initiation of specific immunosuppressive treatment with dexamethasone, immunoglobulins and anakinra, the patient completely recovered and could finally be discharged after a 2­week stay in hospital. Furthermore, the current diagnostic and therapeutic options are discussed. Ferritin is a decisive diagnostic marker that should be determined in every patient with unclear organ failure.

C-reactive protein for risk prediction of post-operative delirium and post-operative neurocognitive disorder.

BACKGROUND: Post-operative delirium (POD) and post-operative neurocognitive disorder (NCD) are frequently seen in the elderly. Development of biomarkers for pre-operative risk prediction is of major relevance. As inflammation present before surgery might predispose to POD and post-operative NCD development, we aim to determine associations between pre-operative C-reactive protein (CRP) and the incidence of POD and post-operative NCD. METHODS: In this observational study, we analyzed 314 patients enrolled in the SuDoCo trial, who had a pre-operative CRP measurement the day before surgery. Primary outcomes were POD assessed according DSM-4 from day 1 until day 7 after surgery and post-operative NCD assessed 3 months after surgery. We conducted multivariable logistic regression analysis adjusted for age, sex, randomization, body mass index, MMSE, ASA status, infection/autoimmune disease/malignoma and types of surgery to determine associations between CRP with POD and post-operative NCD, respectively. RESULTS: Pre-operative CRP was independently associated with POD [OR 1.158 (95% CI 1.040, 1.291); P = .008]. Patients with CRP values ≥5 mg/dL had a 4.8-fold increased POD risk [OR 4.771 (95% CI 1.765, 12.899; P = .002)] compared to patients with lower CRP values. However, no association was seen between pre-operative CRP and post-operative NCD [OR 0.552 (95% CI 0.193, 1.581); P = .269]. CONCLUSIONS: Pre-operative CRP levels were independently associated with POD but not post-operative NCD after three months. Moreover, higher pre-operative CRP levels showed higher risk for POD. This strengthens the role of inflammation in the development of POD. Assessment of CRP before surgery might allow risk stratification of POD. TRIAL REGISTRATION: This study was registered with ISRCTN Register 36437985 on 02 March 2009.

Risk Factors of Intraoperative Dysglycemia in Elderly Surgical Patients.

BACKGROUNDː Dysglycemia is associated with adverse outcome including increased morbidity and mortality in surgical patients. Acute insulin resistance due to the surgical stress response is seen as a major cause of so-called stress hyperglycemia. However, understanding of factors determining blood glucose (BG) during surgery is limited. Therefore, we investigated risk factors contributing to intraoperative dysglycemia. METHODSː In this subgroup investigation of the BIOCOG study, we analyzed 87 patients of ≥ 65 years with tight intraoperative BG measurement every 20 min during elective surgery. Dysglycemia was defined as at least one intraoperative BG measurement outside the recommended target range of 80-150 mg/dL. Additionally, all postoperative BG measurements in the ICU were obtained. Multivariable logistic regression analysis adjusted for age, sex, American Society of Anesthesiologists (ASA) status, diabetes, type and duration of surgery, minimum Hemoglobin (Hb) and mean intraoperative norepinephrine use was performed to identify risk factors of intraoperative dysglycemia. RESULTSː 46 (52.9%) out of 87 patients developed intraoperative dysglycemia. 31.8% of all intraoperative BG measurements were detected outside the target range. Diabetes [OR 9.263 (95% CI 2.492, 34.433); p=0.001] and duration of surgery [OR 1.005 (1.000, 1.010); p=0.036] were independently associated with the development of intraoperative dysglycemia. Patients who experienced intraoperative dysglycemia had significantly elevated postoperative mean (p<0.001) and maximum BG levels (p=0.001). Length of ICU (p=0.007) as well as hospital stay (p=0.012) were longer in patients with dysglycemia. CONCLUSIONSː Diabetes and duration of surgery were confirmed as independent risk factors for intraoperative dysglycemia, which was associated with adverse outcome. These patients, therefore, might require intensified glycemic control. Increased awareness and management of intraoperative dysglycemia is warranted.