Epidural anesthesia in liver surgery - a propensity-score matched analysis

Einleitung: Leberteilresektionen gehen mit starken postoperativen Schmerzen einher. Als Analgesieverfahren stehen grundsätzlich eine systemische Schmerztherapie sowie lokalregionale Verfahren zur Verfügung. Ein Periduralkatheter (PDK) bietet als rückenmarksnahes Verfahren eine suffiziente postoperative Analgesie. In der Leberchirurgie wird der PDK jedoch aufgrund der Gefahr von Gerinnungsstörungen zurückhaltend eingesetzt, sodass die verfügbaren Daten für dieses Patientenkollektiv begrenzt sind. Gegenstand der vorliegenden Dissertation war der Einfluss des PDK auf den postoperativen Verlauf nach einer Leberteilresektion. Methodik: Eine Subgruppe von N = 254 Patienten der PHYDELIO-Studie (Perioperative Gabe von Physostigmin bei Leberteilresektion zur Prophylaxe von Delir und postoperativem kognitiven Defizit) bildete die Grundlage der Analysen. Primärer Endpunkt war die Inzidenz interventions-würdiger Schmerzen am ersten postoperativen Tag. Sekundäre Endpunkte waren postoperative Komplikationen, die Krankenhausverweildauer sowie das 1-Jahresüberleben. Postoperative Schmerzen wurden durch die Numerische Rating Skala (NRS) erfasst. Die postoperativen Kom-plikationen wurden nach Clavien-Dindo klassifiziert. Aufgrund von Gruppenunterschieden bei den Basischarakteristika erfolgte ein 1:1 Propensity-Score Matching. Im Anschluss daran bezogen sich weitere Untersuchungen auf N = 55 Patienten mit und N = 55 Patienten ohne PDK. Unterschiede in den Gruppen in Bezug auf die Zielgrößen wurden durch Tests für verbundene Stichproben ermittelt. Ergebnisse: Die Inzidenz des interventionswürdigen postoperativen Schmerzes betrug am ersten postoperativen Tag 25 % in der PDK-Gruppe und 60 % in der Nicht-PDK-Gruppe. Unabhängig von Alter, Geschlecht, Charlson‘s Komorbiditätsindex, präoperativen Schmerzen und chirurgischem Zugang (offen versus laparoskopisch) hatten die Patienten mit PDK ein signifikant geringeres Risiko, Schmerzen NRS 5 zu erfahren [Odds ratio (95 % Konfidenzintervall (KI)): 0,06 (0,01–0,28); p 0,999 be-ziehungsweise p = 0,467). Patienten mit PDK hatten einen signifikanten Überlebensvorteil bis zu einem Jahr nach der OP [Hazard ratio (95 % KI): 0,32 (0,11–0,90); p = 0,031]. Zusammenfassung: Durch den Einsatz des PDK konnte eine überlegene Analgesie nach Leberteilresektion erzielt werden. Ferner zeigte sich eine Reduktion der 1-Jahresletalität. Dennoch ist der nachgewiesene Nutzen gegen das Risiko eines Epiduralhämatoms sorgfältig abzuwägen, sodass die Entscheidung für das Verfahren bei Patienten in der Leberchirurgie letztlich einer Individualentscheidung bedarf.  Der nachfolgende Text entspricht dem Abstrakt der Arbeit „Epidural Anesthesia in Liver Surgery – A Propensity-Score Matched Analysis“ https://doi.org/10.1093/pm/pnaa130 Objective: To assess the effects of EA on patients who underwent liver resection. Design: Secondary analysis of a prospective randomized-controlled trial. Setting: This single centre study was conducted at an academic medical centre. 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 at movement, on postoperative days (POD) 1–5, analyzed with logistic mixed effects models; and postoperative complications according to the Clavien-Dindo classification, length of hospital stay (LOS), and 1-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 [95 % confidence interval, CI]: 0.06 [0.01–0.28]; p 0.999, and p = 0.467, respectively). Reduced mortality rates were seen in the EA group one year after surgery (9.1 % versus 30.9 %; hazard ratio [95 % CI]: 0.32 [0.11–0.90]; p = 0.031). No EA-related adverse events occurred. Earlier recovery of bowel function was seen in EA patients. Conclusion: Patients with EA had better postoperative pain control and required less systemic opioids. Postoperative complications and LOS did not differ, although 1-year survival was significantly improved in patients with EA. EA applied in liver surgery was effective and safe

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

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

Circadian rhythms in septic shock patients

Background: Despite the intensive efforts to improve the diagnosis and therapy of sepsis over the last decade, the mortality of septic shock remains high and causes substantial socioeconomical burden of disease. The function of immune cells is time-of-day-dependent and is regulated by several circadian clock genes. This study aims to investigate whether the rhythmicity of clock gene expression is altered in patients with septic shock. Methods: This prospective pilot study was performed at the university hospital Charite-Universitatsmedizin Berlin, Department of Anesthesiology and Operative Intensive Care Medicine (CCM, CVK). We included 20 patients with septic shock between May 2014 and January 2018, from whom blood was drawn every 4 h over a 24-h period to isolate CD14-positive monocytes and to measure the expression of 17 clock and clock-associated genes. Of these patients, 3 whose samples expressed fewer than 8 clock genes were excluded from the final analysis. A rhythmicity score S-P was calculated, which comprises values between -1 (arrhythmic) and 1 (rhythmic), and expression data were compared to data of a healthy study population additionally. Results: 77% of the measured clock genes showed inconclusive rhythms, i.e., neither rhythmic nor arrhythmic. The clock genes NR1D1, NR1D2 and CRY2 were the most rhythmic, while CLOCK and ARNTL were the least rhythmic. Overall, the rhythmicity scores for septic shock patients were significantly (p < 0.0001) lower (0.23 +/- 0.26) compared to the control group (12 healthy young men, 0.70 +/- 0.18). In addition, the expression of clock genes CRY1, NR1D1, NR1D2, DBP, and PER2 was suppressed in septic shock patients and CRY2 was significantly upregulated compared to controls. Conclusion: Molecular rhythms in immune cells of septic shock patients were substantially altered and decreased compared to healthy young men. The decrease in rhythmicity was clock gene-dependent. The loss of rhythmicity and down-regulation of clock gene expression might be caused by sepsis and might further deteriorate immune responses and organ injury, but further studies are necessary to understand underlying pathophysiological mechanisms

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

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