Effect of oral taurine on morbidity and mortality in elderly hip fracture patients: a randomized trial.

Hip fracture patients represent a large part of the elderly surgical population and face severe postoperative morbidity and excessive mortality compared to adult surgical hip fracture patients. Low antioxidant status and taurine deficiency is common in the elderly, and may negatively affect postoperative outcome. We hypothesized that taurine, an antioxidant, could improve clinical outcome in the elderly hip fracture patient. A double blind randomized, placebo controlled, clinical trial was conducted on elderly hip fracture patients. Supplementation started after admission and before surgery up to the sixth postoperative day. Markers of oxidative status were measured during hospitalization, and postoperative outcome was monitored for one year after surgery. Taurine supplementation did not improve in-hospital morbidity, medical comorbidities during the first year, or mortality during the first year. Taurine supplementation lowered postoperative oxidative stress, as shown by lower urinary 8-hydroxy-2-deoxyguanosine levels (Generalized estimating equations (GEE) analysis average difference over time; regression coefficient (Beta): -0.54; 95% CI: -1.08--0.01; p = 0.04), blunted plasma malondialdehyde response (Beta: 1.58; 95% CI: 0.00-3.15; p = 0.05) and a trend towards lower lactate to pyruvate ratio (Beta: -1.10; 95% CI: -2.33-0.12; p = 0.08). We concluded that peri-operative taurine supplementation attenuated postoperative oxidative stress in elderly hip fracture patients, but did not improve postoperative morbidity and mortality.

Preoperative cerebrospinal fluid cytokine levels and the risk of postoperative delirium in elderly hip fracture patients.

BACKGROUND: Aging and neurodegenerative disease predispose to delirium and are both associated with increased activity of the innate immune system resulting in an imbalance between pro- and anti-inflammatory mediators in the brain. We examined whether hip fracture patients who develop postoperative delirium have altered levels of inflammatory mediators in cerebrospinal fluid (CSF) prior to surgery. METHODS: Patients were 75 years and older and admitted for surgical repair of an acute hip fracture. CSF samples were collected preoperatively. In an exploratory study, we measured 42 cytokines and chemokines by multiplex analysis. We compared CSF levels between patients with and without postoperative delirium and examined the association between CSF cytokine levels and delirium severity. Delirium was diagnosed with the Confusion Assessment Method; severity of delirium was measured with the Delirium Rating Scale Revised-98. Mann-Whitney U tests or Student t-tests were used for between-group comparisons and the Spearman correlation coefficient was used for correlation analyses. RESULTS: Sixty-one patients were included, of whom 23 patients (37.7%) developed postsurgical delirium. Concentrations of Fms-like tyrosine kinase-3 (P=0.021), Interleukin-1 receptor antagonist (P=0.032) and Interleukin-6 (P=0.005) were significantly lower in patients who developed delirium postoperatively. CONCLUSIONS: Our findings fit the hypothesis that delirium after surgery results from a dysfunctional neuroinflammatory response: stressing the role of reduced levels of anti-inflammatory mediators in this process. TRIAL REGISTRATION: The Effect of Taurine on Morbidity and Mortality in the Elderly Hip Fracture Patient. REGISTRATION NUMBER: NCT00497978. Local ethical protocol number: NL16222.094.07.

The neuropsychological sequelae of delirium in elderly patients with hip fracture three months after hospital discharge.

BACKGROUND: Delirium is a risk factor for long-term cognitive impairment and dementia. Yet, the nature of these cognitive deficits is unknown as is the extent to which the persistence of delirium symptoms and presence of depression at follow-up may account for the association between delirium and cognitive impairment at follow-up. We hypothesized that inattention, as an important sign of persistent delirium and/or depression, is an important feature of the cognitive profile three months after hospital discharge of patients who experienced in-hospital delirium. METHODS: This was a prospective cohort study. Fifty-three patients aged 75 years and older were admitted for surgical repair of acute hip fracture. Before the surgery, baseline characteristics, depressive symptomatology, and global cognitive performance were documented. The presence of delirium was assessed daily during hospital admission and three months after hospital discharge when patients underwent neuropsychological assessment. RESULTS: Of 27 patients with in-hospital delirium, 5 were still delirious after three months. Patients with in-hospital delirium (but free of delirium at follow-up) showed poorer performance than patients without in-hospital delirium on tests of global cognition and episodic memory, even after adjustment for age, gender, and baseline cognitive impairment. In contrast, no differences were found on tests of attention. Patients with in-hospital delirium showed an increase of depressive symptoms after three months. However, delirium remained associated with poor performance on a range of neuropsychological tests among patients with few or no signs of depression at follow-up. CONCLUSION: Elderly hip fracture patients with in-hospital delirium experience impairments in global cognition and episodic memory three months after hospital discharge. Our results suggest that inattention, as a cardinal sign of persistent delirium or depressive symptomatology at follow-up, cannot fully account for the poor cognitive outcome associated with delirium.

Reducing postoperative fasting times by implementing a food service in the Post Anaesthesia Care Unit (PACU).

BACKGROUND & AIMS: Early oral postoperative nutrition is a proven beneficial element of postoperative care, resulting in improvement in quality of life and a shorter hospital stay. Guidelines state that postoperative oral nutrition can safely be started within the first hours after surgery. However, oral nutrition is mainly investigated starting from postoperative day one (POD1). This pragmatic study assessed whether a food service in the Post Anaesthesia Care Unit (PACU) may reduce postoperative fasting times on postoperative day zero (POD0) early after surgery on this high care unit. The primary outcome was postoperative fasting time in the PACU. Secondary outcomes were postoperative patient experiences and nutritional tolerance. METHODS: This pragmatic prospective before-after study, included adult patients with a planned overnight stay in the PACU, and without anticipated postoperative dietary restrictions. A food service was developed, allowing re-uptake of oral nutrition early after surgery, already at POD0. Postoperative fasting time in the PACU was defined as the duration of time between the moment of arrival at the PACU, until first postoperative intake or until 9 a.m. on POD1, when most patients were discharged to the surgical ward. Secondary outcomes such as postoperative patient experiences and nutritional tolerance were scored on POD0 at 8 p.m. and on POD1 at 8 a.m. RESULTS: A total of 235 patients were included, 119 in the pre-implementation (control) and 116 in the post-implementation (intervention) group. Mean postoperative fasting time was reduced by a mean of 6.0 h (95% CI 4.8-7.4, p-value ≤ .001), from 17.5 h in controls to 11.5 h in the intervention group. In the intervention group, 45% of patients had nutritional intake on POD0 (8 p.m.), increasing to 80% of patients on POD1 (8 a.m.), compared to no intake at both time-points in the control group. In the intervention group, average patient satisfaction increased over time. Flatus frequency was higher in the intervention group on POD1 (45% vs. 22%, p-value ≤ .001), while postoperative nausea and/or vomiting, and usage of anti-emetic medication were not different between groups. CONCLUSIONS: In a heterogeneous group of adult post-surgical patients with a planned overnight stay in the PACU, implementation of a food service resulted in a significant and clinically relevant reduction of postoperative fasting time, and increased patient satisfaction without compromising nutritional tolerance. Registered at www.isrctn.org with study ID ISRCTN17976930.

Antioxidant-enriched enteral nutrition and immuno-inflammatory response after major gastrointestinal tract surgery.

Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery. The objective of the study was to investigate the effect of an enteral supplement, containing glutamine and antioxidants, on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery. Patients (n 21) undergoing major gastrointestinal tract surgery were randomised in a single-centre, open-label study. The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1, 3, 5 and 7 after surgery. Major gastrointestinal surgery increased IL-6, TNF receptor 55/60 (TNF-R55) and C-reactive protein (CRP). Surgery reduced human leucocyte antigen-DR (HLA-DR) expression on monocytes. CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group. In the treatment group, from the moment Module AOX was administered on day 1 after surgery, TNF receptor 75/80 (TNF-R75) level decreased until the third post-operative day and then stabilised, whereas in the control group the TNF-R75 level continued to increase. The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response (CRP, TNF-R75) after surgery.

Antioxidant enriched enteral nutrition and oxidative stress after major gastrointestinal tract surgery.

AIM: To investigate the effects of an enteral supplement containing antioxidants on circulating levels of antioxidants and indicators of oxidative stress after major gastrointestinal surgery. METHODS: Twenty-one patients undergoing major upper gastrointestinal tract surgery were randomised in a single centre, open label study on the effect of postoperative enteral nutrition supplemented with antioxidants. The effect on circulating levels of antioxidants and indicators of oxidative stress, such as F2-isoprostane, was studied. RESULTS: The antioxidant enteral supplement showed no adverse effects and was well tolerated. After surgery a decrease in the circulating levels of antioxidant parameters was observed. Only selenium and glutamine levels were restored to pre-operative values one week after surgery. F2-isoprostane increased in the first three postoperative days only in the antioxidant supplemented group. Lipopolysaccharide binding protein (LBP) levels decreased faster in the antioxidant group after surgery. CONCLUSION: Despite lower antioxidant levels there was no increase in the circulating markers of oxidative stress on the first day after major abdominal surgery. The rise in F2-isoprostane in patients receiving the antioxidant supplement may be related to the conversion of antioxidants to oxidants which raises questions on antioxidant supplementation. Module AOX restored the postoperative decrease in selenium levels. The rapid decrease in LBP levels in the antioxidant group suggests a possible protective effect on gut wall integrity. Further studies are needed on the role of oxidative stress on outcome and the use of antioxidants in patients undergoing major abdominal surgery.

Effects of a Carbohydrate-, Glutamine-, and Antioxidant-Enriched Oral Nutrition Supplement on Major Surgery-Induced Insulin Resistance: A Randomized Pilot Study.

BACKGROUND: Insulin resistance after surgery hampers recovery. Oxidative stress is shown to be involved in the occurrence of postoperative insulin resistance. Preoperative carbohydrate-rich oral nutrition supplements reduce but do not prevent insulin resistance. The aim of the present study was to investigate the effect of a carbohydrate-, glutamine-, and antioxidant-enriched preoperative oral nutrition supplement on postoperative insulin resistance. METHODS: A double-blind randomized controlled pilot study in 18 patients with rectal cancer, who received either the supplement (S) or the placebo (P) 15, 11, and 4 hours preoperatively, was conducted. Insulin sensitivity was studied prior to surgery and on the first postoperative day using a hyperinsulinemic euglycemic 2-step clamp. RESULTS: Hepatic insulin sensitivity (insulin-mediated suppression of glucose production) decreased significantly after surgery in both groups, with no differences between the groups. Peripheral insulin sensitivity (glucose rate of disappearance, Rd) was significantly decreased after surgery in both groups (S: 37.2 [19.1-50.9] vs 20.6 [13.9-27.9]; P: 23.8 [15.7-35.5] vs 15.3 [12.6-19.1] µmol/kg·min) but less pronounced in the supplemented group (P = .04). The percentage decrease in glucose Rd did not differ between the groups. Adipose tissue insulin sensitivity (insulin-mediated suppression of plasma free fatty acids) decreased to the same extent after surgery in both groups. CONCLUSION: Rectal cancer surgery induced profound insulin resistance, affecting glucose and fatty acid metabolism. The preoperative nutrition supplement somewhat attenuated but did not prevent postoperative peripheral insulin resistance.

Taurine Concentrations Decrease in Critically Ill Patients With Shock Given Enteral Nutrition.

BACKGROUND: Nutrition studies in the intensive care unit (ICU) have shown that adequate enteral nutrition (EN) support has clinical benefits. However, the course of amino acid concentrations in plasma has never been investigated in patients admitted with shock receiving EN. We hypothesized that plasma concentrations, when deficit, increase during EN and that persistent deficiency is associated with poor outcome. METHODS: In 33 septic or cardiogenic shock patients receiving EN, plasma amino acid concentrations were measured during 5 days. Changes in amino acid concentrations, correlations with clinical outcome variables, and regression analyses were studied. RESULTS: On ICU admission, several plasma concentrations were deficient. Plasma concentrations of almost all amino acids increased. In contrast, taurine decreased by >50%, from 47.6 µmol/L on admission to 20.0 µmol/L at day 1, and remained low at day 5. Taurine (admission) correlated with time on mechanical ventilation (R = -0.42, P = .015). Taurine decrease within 24 hours correlated with Acute Physiology and Chronic Health Evaluation II predicted mortality (R = 0.43, P = .017) and Sequential Organ Failure Assessment score (R = 0.36, P = .05). Regression analyses confirmed correlations. CONCLUSIONS: Several amino acids were deficient in plasma on ICU admission but increased during EN. Taurine concentrations declined and were associated with longer periods of mechanical ventilation and ICU support. Fast taurine decline correlated with severity of organ failure. These findings support the role of taurine during ischemia, reperfusion, and inflammation. Taurine may be an essential candidate to enrich nutrition support for critically ill patients, although more research is required.

Preoperative nutrition status and postoperative outcome in elderly general surgery patients: a systematic review.

BACKGROUND: Poor nutrition status is considered a risk factor for postoperative complications in the adult population. In elderly patients, who often have a poor nutrition status, this relationship has not been substantiated. Thus, the aim of this systematic review was to assess the merit of preoperative nutrition parameters used to predict postoperative outcome in elderly patients undergoing general surgery. METHODS: A systematic literature search of 10 consecutive years, 1998-2008, in PubMed, EMBASE, and Cochrane databases was performed. Search terms used were nutrition status, preoperative assessment, postoperative outcome, and surgery (hip or general), including their synonyms and MeSH terms. Limits used in the search were human studies, published in English, and age (65 years or older). Articles were screened using inclusion and exclusion criteria. All selected articles were checked on methodology and graded. RESULTS: Of 463 articles found, 15 were included. They showed profound heterogeneity in the parameters used for preoperative nutrition status and postoperative outcome. The only significant preoperative predictors of postoperative outcome in elderly general surgery patients were serum albumin and ≥ 10% weight loss in the previous 6 months. CONCLUSIONS: This systematic review revealed only 2 preoperative parameters to predict postoperative outcome in elderly general surgery patients: weight loss and serum albumin. Both are open to discussion in their use as a preoperative nutrition parameter. Nonetheless, serum albumin seems a reliable preoperative parameter to identify a patient at risk for nutrition deterioration and related complicated postoperative course.

Predicting delirium duration in elderly hip-surgery patients: does early symptom profile matter?

Background. Features that may allow early identification of patients at risk of prolonged delirium, and therefore of poorer outcomes, are not well understood. The aim of this study was to determine if preoperative delirium risk factors and delirium symptoms (at onset and clinical symptomatology during the course of delirium) are associated with delirium duration. Methods. This study was conducted in prospectively identified cases of incident delirium. We compared patients experiencing delirium of short duration (1 or 2 days) with patients who had more prolonged delirium (≥3 days) with regard to DRS-R-98 (Delirium Rating Scale Revised-98) symptoms on the first delirious day. Delirium symptom profile was evaluated daily during the delirium course. Results. In a homogenous population of 51 elderly hip-surgery patients, we found that the severity of individual delirium symptoms on the first day of delirium was not associated with duration of delirium. Preexisting cognitive decline was associated with prolonged delirium. Longitudinal analysis using the generalised estimating equations method (GEE) identified that more severe impairment of long-term memory across the whole delirium episode was associated with longer duration of delirium. Conclusion. Preexisting cognitive decline rather than severity of individual delirium symptoms at onset is strongly associated with delirium duration.

Human taurine metabolism: fluxes and fractional extraction rates of the gut, liver, and kidneys.

Taurine is involved in numerous biological processes. However, taurine plasma level decreases in response to pathological conditions, suggesting an increased need. Knowledge on human taurine metabolism is scarce and only described by arterial-venous differences across a single organ. Here we present taurine organ fluxes using arterial-venous concentration differences combined with blood flow measurements across the 3 major organ systems involved in human taurine metabolism in patients undergoing hepatic surgery. In these patients, we collected blood from an arterial line, portal vein, hepatic vein, and renal vein, and determined blood flow of the hepatic artery, portal vein, and renal vein using Doppler ultrasound. Plasma taurine was determined by high-performance liquid chromatography, and net organ fluxes and fractional extraction rates were calculated. Seventeen patients were studied. No differences were found between taurine concentrations in arterial, portal venous, hepatic venous, and renal venous plasma. The only significant finding was a release of taurine by the portally drained viscera (P = .04). Our data show a net release of taurine by the gut. This probably is explained by the enterohepatic cycle of taurine. Future studies on human taurine metabolism are required to determine whether taurine is an essential aminosulfonic acid during pathological conditions and whether it should therefore be supplemented.

Cerebrospinal fluid ß-amyloid and tau are not associated with risk of delirium: a prospective cohort study in older adults with hip fracture.

OBJECTIVES: To examine the association between cerebrospinal fluid (CSF) ß-amyloid (Aß1-42), tau, and hyperphosphorylated tau (Ptau) and risk of delirium in older adults with hip fracture. DESIGN: Prospective cohort study. SETTING: University-affiliated general hospital in Alkmaar, the Netherlands. PARTICIPANTS: Seventy-six participants aged 75 and older admitted for surgical repair of acute hip fracture. MEASUREMENTS: Presurgical baseline screening and assessment included the Informant Questionnaire on Cognitive Decline-short form (IQCODE-N), Mini-Mental State Examination, standardized Snellen test for visual impairment, Geriatric Depression Scale, Barthel Index (BI), and Lawton Instrumental Activity of Daily Living (IADL) scale. The number of medical comorbidities and medications at home, American Society of Anesthesiologists score, and Acute Physiology and Chronic Health Evaluation II score were determined according to chart review. Delirium was diagnosed using the Confusion Assessment Method. CSF was collected at the onset of spinal anesthesia. RESULTS: Postoperative delirium occurred in 30 (39.5%) participants. Participants with delirium were older, showed more signs of cognitive decline, were more dependent at home in activity of daily living and IADL functioning, and used more medications before admission. Preoperative CSF Aß1-42, tau, and Ptau levels were not significantly different in participants who did and did not develop delirium during subsequent hospitalization. In contrast, prefracture cognitive decline (IQCODE-N) was significantly related to delirium (odds ratio=9.43, 95% confidence interval=2.45-36.31). CONCLUSION: Cognitive impairment predisposes to delirium, but in this study, postoperative delirium was not associated with baseline CSF Aß1-42, tau, and Ptau levels. These findings suggest that CSF markers for plaque and tangle formation are not strongly associated with delirium risk in older adults with hip fracture.