Maren Schmidt

Insulin-related decrease in cerebral glucose despite normoglycemia in aneurysmal subarachnoid hemorrhage

IntroductionHyperglycaemia following aneurysmal subarachnoid hemorrhage (SAH) is associated with complications and impaired neurological recovery. The aim of this study was to determine the effect of insulin treatment for glucose control on cerebral metabolism in SAH patients.MethodsThis prospective, nonrandomized study was conducted in 31 SAH patients in an intensive care unit (age 52 ± 10 years, World Federation of Neurological Surgeons grade 2.9 ± 1.6). A microdialysis catheter was inserted into the vascular territory of the aneurysm after clipping. Blood glucose levels above 140 mg/dl were treated with intravenous insulin and the microdialysates were analyzed hourly for the first 12 hours of infusion.ResultsNo hypoglycaemia occurred. Twenty-four patients were treated with insulin for glucose control. Higher age and World Federation of Neurological Surgeons score were risk factors for need for insulin treatment (P < 0.05). Although blood glucose remained stable after initiation of insulin infusion, insulin induced a significant decrease in cerebral glucose at 3 hours after onset of the infusion until the end of the observation period (P < 0.05), reflecting high glucose utilization. The lactate:pyruvate ratio and glutamate did not increase, excluding ischaemia as possible cause of the decrease in glucose. Glycerol tended toward higher values at the end of the observation period (9 to 12 hours), reflecting either tissue damage after SAH or the beginning of cellular distress after insulin infusion.ConclusionHigher SAH grade was among the risk factors for need for insulin. Intensive glycaemic control using insulin induced a decrease of cerebral glucose and a slight increase in glycerol, though blood glucose remained normal. Future studies might detect relevant metabolic derangements when insulin treatment starts at low cerebral glucose levels, and may allow us to design a strategy for avoidance of insulin-induced metabolic crisis in SAH patients.

Dose-dependent effects of erythropoietin in propofol anesthetized neonatal rats

Exposure to Gamma-aminobutyric-acid (GABA)(A)-receptor agonists and N-Methyl-D-Aspartate (NMDA)-antagonists has been demonstrated to induce neurodegeneration in newborn rats. Exogenous erythropoietin (EPO) protects against NMDA antagonist-mediated neuronal death. In this study we evaluated whether EPO is also effective in limiting neurodegeneration of the GABA(A)-mimetic agent propofol in newborn rats. 6 day old rats were randomized to one of four groups and treated with intraperitoneal applications of 3 x 30 mg/kg propofol at 0, 90 and 180 min, propofol in combination with 5000 IU/kg rEPO, propofol in combination with 20,000 IU/kg rEPO or sham injections of PAD II solution as controls. After 24h, brains of the animals were histopathologically examined and a summation score of degenerated cells was calculated for every brain. Propofol increased neuronal degeneration scores from 16,090+/-4336 to 28,860+/-6569 (p<0.01). This effect was completely abolished by low-dose rEPO (14,270+/-4542, p<0.001 versus propofol only; p>0.05 versus controls). In contrast, high-dose rEPO was not protective (23 930+/-8896, p>0.05 versus propofol only). Propofol may cause neuronal death in newborn rat brains, which is prevented by low-dose rEPO but not high-dose rEPO.

Patient Empowerment Improved Perioperative Quality of Care in Cancer Patients Aged ≥ 65 Years – A Randomized Controlled Trial

Purpose This randomized controlled, clinical prospective interventional trial was aimed at exploring the effect of patient empowerment on short- and long-term outcomes after major oncologic surgery in elderly cancer patients. Methods This trial was performed from February 2011 to January 2014 at two tertiary medical centers in Germany. The study included patients aged 65 years and older undergoing elective surgery for gastro-intestinal, genitourinary, and thoracic cancer. The patients were randomly assigned to the intervention group, i.e. patient empowerment through information booklet and diary keeping, or to the control group, which received standard care. Randomization was done by block randomization in blocks of four in order of enrollment. The primary outcome were 1,postoperative length of hospital stay (LOS) and 2. long-term global health-related quality of life (HRQoL) one year postoperatively. HRQoL was assessed using the EORTC QLQ C30 questionnaire. Secondary outcomes encompassed postoperative stress and complications. Further objectives were the identification of predictors of LOS, and HRQoL at 12 months. Results Overall 652 patients were included. The mean age was 72 ± 4.9 years, and the majority of patients were male (68.6%, n = 447). The ^median of postoperative length of stay was 9 days (IQR 7–14 day). There were no significant differences between the intervention and the control groups in postoperative LOS (p = 0.99) or global HRQoL after one year (women: p = 0.54, men: p = 0.94). While overall complications and major complications occurred in 74% and 24% of the cases, respectively, frequency and severity of complications did not differ significantly between the groups. Patients in the intervention group reported significantly less postoperative pain (p = 0.03) than the control group. Independent predictors for LOS were identified as severity of surgery, length of anesthesia, major postoperative complications, nutritional state, and pre-operative physical functional capacity measured by the Timed Up and Go-test by multiple robust regressions. Conclusion Patient empowerment through information booklet and diary keeping did not shorten the postoperative LOS in elderly onco-surgical patients, but improved quality of care regarding postoperative pain. Postoperative length of stay is influenced by pre-operative nutritional state, pre-operative functional impairment, severity of surgery, and length of anesthesia. Trial Registration Clinicaltrials.gov. Identifier NCT01278537

Prediction of Long-Term Mortality by Preoperative Health-Related Quality-of-Life in Elderly Onco-Surgical Patients

Objective Aim of this study was to evaluate the association between preoperative health-related quality of life (HRQoL) and mortality in a cohort of elderly patients (>65 years) with gastrointestinal, gynecological and genitourinary carcinomas. Design Prospective cohort pilot study. Setting Tertiary university hospital in Germany. Patients Between June 2008 and July 2010 and after ethical committee approval and written informed consent, 126 patients scheduled for onco-surgery were included. Prior to surgery as well as 3 and 12 months postoperatively all participants completed the EORTC-QLQ-C30 questionnaire (measuring self-reported health-related quality of life). Additionally, demographic and clinical data including the Mini Mental State Examination (MMSE) were collected. Surgery and anesthesia were conducted according to the standard operating procedures. Primary endpoint was the cumulative mortality rate over 12 months after one year. Changes in Quality of life were considered as secondary outcome. Results Mortality after one year was 28%. In univariable and multivariable logistic regression analysis baseline HRQoL self-reported cognitive function (OR per point: 0.98; CI 95% 0.96–0.99; p = 0.024) and higher symptom burden for appetite loss (per point: OR 1.02; CI 95% 1.00–1.03; p = 0.014) were predictive for long-term mortality. Additionally the MMSE as an objective measure of cognitive impairment (per point: OR 0.69; CI 95% 0.51–0.96; p = 0.026) as well as severity of surgery (OR 0.31; CI 95% 0.11–0.93; p = 0.036) were predictive for long-term mortality. Global health status 12 months after surgery was comparable to the baseline levels in survivors despite moderate impairments in other domains. Conclusion This study showed that objective and self-reported cognitive functioning together with appetite loss were prognostic for mortality in elderly cancer patients. In addition, impaired cognitive dysfunction and severity of surgery were predictive for one-year mortality whereas in this selected population scheduled for surgery age, gender, cancer site and metastases were not.

High-dose Propofol Triggers Short-term Neuroprotection and Long-term Neurodegeneration in Primary Neuronal Cultures from Rat Embryos

This study investigated the effects of propofol on primary neuronal cultures from rat embryos. Primary cortical neuronal cultures were prepared from Wistar rat embryos (E18). The viability of cells exposed to 0.01, 0.1 or 1 mg/ml propofol for up to 48 h was assessed using a methyltetrazolium assay. In order to evaluate the role of γ-aminobutyric acid-A (GABAA) receptors, cells were also pre-incubated with the GABAA-receptor antagonists, gabazine and picrotoxin. Propofol at a concentration of 1 mg/ml significantly reduced cell viability after 12 h. In contrast, this concentration led to a significant increase in cell viability at 3 and 6 h. The GABAA-receptor antagonists did not influence the neurodegenerative effect of propofol but abolished its neuroprotective effect. DNA fragmentation as a marker of apoptosis was elevated after 24 h propofol treatment. These results confirm that high doses of propofol can cause GABAA-receptor triggered neuroprotection and a subsequent time-dependent, but GABAA-independent, neurodegeneration in primary cortical neurons.

Predictors of survival in critically ill patients with acute respiratory distress syndrome (ARDS): an observational study.

BackgroundCurrently there is no ARDS definition or classification system that allows optimal prediction of mortality in ARDS patients. This study aimed to examine the predictive values of the AECC and Berlin definitions, as well as clinical and respiratory parameters obtained at onset of ARDS and in the course of the first seven consecutive days.MethodsThe observational study was conducted at a 14-bed intensive care unit specialized on treatment of ARDS. Predictive validity of the AECC and Berlin definitions as well as PaO2/FiO2 and FiO2/PaO2*Pmean (oxygenation index) on mortality of ARDS patients was assessed and statistically compared.ResultsFour hundred forty two critically-ill patients admitted for ARDS were analysed. Multivariate Cox regression indicated that the oxygenation index was the most accurate parameter for mortality prediction. The third day after ARDS criteria were met at our hospital was found to represent the best compromise between earliness and accuracy of prognosis of mortality regarding the time of assessment. An oxygenation index of 15 or greater was associated with higher mortality, longer length of stay in ICU and hospital and longer duration of mechanical ventilation. In addition, non-survivors had a significantly longer length of stay and duration of mechanical ventilation in referring hospitals before admitted to the national reference centre than survivors.ConclusionsThe oxygenation index is suggested to be the most suitable parameter to predict mortality in ARDS, preferably assessed on day 3 after admission to a specialized centre. Patients might benefit when transferred to specialized ICU centres as soon as possible for further treatment.

Functional impairment prior to major non-cardiac surgery is associated with mortality within one year in elderly patients with gastrointestinal, gynaecological and urogenital cancer: A prospective observational cohort study

OBJECTIVE To investigate the prognostic value of elements of the Geriatric Assessment, in particular the Timed Up and Go (TUG) Test and the Barthel Index of Activities of Daily Living (ADL) for one-year post-operative mortality in elderly patients with cancer. MATERIALS AND METHODS This prospective cohort study included patients 65years of age or older undergoing elective major surgery for cancer between June 2008 and June 2010. Preoperative functional status was measured by the TUG Test and the Barthel Index of ADL Cognitive state was assessed by the Mini Mental State Examination (MMSE). Complications were recorded prospectively. The degree of resection was noted. RESULTS Data from 131 patients (56% women; median age, 71years) were analysed at 1year of follow-up. Mortality after 1year was 28.2%. Twenty-nine patients (22.3%) were dependent in ADLs, and 43 (35.2%) impaired in TUG. Thirteen patients (10.7%) were both, dependent in ADLs and impaired in TUG. Short-term complications after surgery occurred in 66% of patients, and major complications occurred in 29%. Patients who were dependent in ADLs and impaired in TUG had significantly higher 1-year mortality (OR, 4.5; 95% CI, 1.21-18.25; p=0.034). Lower scores on the MMSE (OR, 0.64; 95% CI, 0.43-0.95; p=0.048) and incomplete surgical resection (OR, 3.25; 95% CI, 1.15-9.20; p=0.026) were independently associated with higher 1-year mortality. CONCLUSION Functional assessments, such as ADL and TUG scores, as well as mild cognitive impairment, are predictors of long-term outcome in elderly cancer patients. TRIAL REGISTRATION German Clinical Trials Register (DRKS 00005150).

Patient Empowerment Reduces Pain in Geriatric Patients After Gynecologic Onco-Surgery: Subgroup Analysis of a Prospective Randomized Controlled Clinical Trial

Purpose: This study aimed to determine the effect of patient empowerment on acute postoperative pain. This research was part of the Patient Empowerment and Risk‐Assessed Treatment to Improve Outcome in the Elderly After Onco‐Surgery Trial. Design: This research was a prospective randomized controlled interventional study. Methods: Patients who underwent gynecologic onco‐surgery were included in this analysis of demographic data, basic characteristics, pain intensity by numeric rating scale, and mode of pain therapy. The intervention included provision of detailed information booklet and patient diary. Findings: Ninety‐one patients were enrolled (treatment group, n = 51; control group, n = 40). With the same medications, pain on the first postoperative day was significantly less severe in the treatment group than in the control group (P = .03). On multivariate logistic regression, patient empowerment had a significant effect on pain intensity (odds ratio, 3.46; 95% confidence interval, 1.35 to 8.86; P = .01). The number needed to treat to decrease pain from severe to mild (numeric rating scale, 5 to 10 to 0 to 4) was 4.35. Conclusions: Patient empowerment significantly reduces postoperative pain in elderly patients undergoing gynecologic cancer surgery.