Geert Meyfroidt

Early versus Late Parenteral Nutrition in Critically Ill Adults

BACKGROUND Controversy exists about the timing of the initiation of parenteral nutrition in critically ill adults in whom caloric targets cannot be met by enteral nutrition alone. METHODS In this randomized, multicenter trial, we compared early initiation of parenteral nutrition (European guidelines) with late initiation (American and Canadian guidelines) in adults in the intensive care unit (ICU) to supplement insufficient enteral nutrition. In 2312 patients, parenteral nutrition was initiated within 48 hours after ICU admission (early-initiation group), whereas in 2328 patients, parenteral nutrition was not initiated before day 8 (late-initiation group). A protocol for the early initiation of enteral nutrition was applied to both groups, and insulin was infused to achieve normoglycemia. RESULTS Patients in the late-initiation group had a relative increase of 6.3% in the likelihood of being discharged alive earlier from the ICU (hazard ratio, 1.06; 95% confidence interval [CI], 1.00 to 1.13; P=0.04) and from the hospital (hazard ratio, 1.06; 95% CI, 1.00 to 1.13; P=0.04), without evidence of decreased functional status at hospital discharge. Rates of death in the ICU and in the hospital and rates of survival at 90 days were similar in the two groups. Patients in the late-initiation group, as compared with the early-initiation group, had fewer ICU infections (22.8% vs. 26.2%, P=0.008) and a lower incidence of cholestasis (P<0.001). The late-initiation group had a relative reduction of 9.7% in the proportion of patients requiring more than 2 days of mechanical ventilation (P=0.006), a median reduction of 3 days in the duration of renal-replacement therapy (P=0.008), and a mean reduction in health care costs of €1,110 (about

Dynamic characteristics of blood glucose time series during the course of critical illness: Effects of intensive insulin therapy and relative association with mortality

1,600) (P=0.04). CONCLUSIONS Late initiation of parenteral nutrition was associated with faster recovery and fewer complications, as compared with early initiation. (Funded by the Methusalem program of the Flemish government and others; EPaNIC ClinicalTrials.gov number, NCT00512122.).

Mining data from intensive care patients

Objectives:To assess the effect of intensive insulin therapy on blood glucose amplitude variation and pattern irregularity in critically ill patients. To assess the association of these blood glucose signal characteristics with hospital mortality, independent of blood glucose level. Design:Retrospective analysis of the databases of two previously published randomized controlled trials. Setting:University hospital, 56-bed adult surgical intensive care unit and 17-bed medical intensive care unit. Patients:One thousand five-hundred forty-eight surgical intensive care unit patients, admitted between February 2000 and January 2001, and 1200 medical intensive care unit patients, admitted between March 2002 and May 2005. Interventions:In the two randomized controlled trials, patients were randomized to receive either intensive insulin therapy (targeting normoglycemia, between 4.4 and 6.1mmol/L) or conventional insulin therapy (infusing insulin when blood glucose levels were >12 mmol/L and stopping at 10 mmol/L). Measurements and Main Results:Intensive insulin therapy significantly lowered mean blood glucose (5.8 vs. 8.4 mmol/L), hyperglycemic index (0.8 vs. 3.2 mmol/L), and glycemic penalty index (26 vs. 53), but it increased the mean daily difference between minimum and maximum blood glucose (mean daily &dgr; blood glucose; 4.0 vs. 3.3 mmol/L). There was no significant effect on the standard deviation of the blood glucose measurements or on jack-knifed approximate entropy. In multivariable logistic regression analysis, corrected for baseline risk factors, blood glucose levels outside the normoglycemic range, higher mean daily &dgr; blood glucose, higher standard deviation blood glucose, and higher jack-knifed approximate entropy were independently associated with hospital mortality. Conclusions:The Leuven intensive insulin therapy strategy increased mean daily &dgr; blood glucose while not affecting standard deviation blood glucose and jack-knifed approximate entropy. Increased blood glucose amplitude variation and pattern irregularity were associated with mortality, irrespective of blood glucose level. The reduced mortality observed with intensive insulin therapy in the Leuven trials cannot be attributed to an effect on blood glucose amplitude variation or entropy. Reducing amplitude variation and entropy of the blood glucose signal, irrespective of blood glucose concentration, may produce clinical benefits.

Is Preoperative Anxiety and Depression Associated with Onset of Delirium After Cardiac Surgery in Older Patients? A Prospective Cohort Study

In this paper we describe the application of data mining methods for predicting the evolution of patients in an intensive care unit. We discuss the importance of such methods for health care and other application domains of engineering. We argue that this problem is an important but challenging one for the current state of the art data mining methods and explain what improvements on current methods would be useful. We present a promising study on a preliminary data set that demonstrates some of the possibilities in this area.

Neuroprotection in acute brain injury: An up-to-date review

OBJECTIVES: To investigate the prevalence of preoperative anxiety and depressive symptoms and their relationship with the occurrence of postcardiac delirium and to describe the evolution of these symptoms from preoperative admission until discharge.

The impact of premorbid diabetic status on the relationship between the three domains of glycemic control and mortality in critically ill patients

Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research.

Novel methods to predict increased intracranial pressure during intensive care and long-term neurologic outcome after traumatic brain injury: development and validation in a multicenter dataset.

Purpose of reviewHyperglycemia, hypoglycemia and increased glycemic variability are independently associated with increased risk of mortality in critically ill patients. The purpose of this review is to evaluate the evidence from interventional trials of intensive insulin therapy, as well as observational cohort studies, relating premorbid diabetic status and these three domains of glycemic control to mortality. Recent findingsHyperglycemia has a stronger association with mortality in critically ill patients without diabetes than in those with diabetes. Hypoglycemia is independently associated with increased risk of mortality in both populations. Limited data suggest that increased glycemic variability may have a stronger association with mortality in patients without diabetes than in those with diabetes. SummaryPremorbid diabetic status impacts the relationship of the three domains of glycemic control to risk of mortality in critically ill patients. The data presented in this review are hypothesis generating; future trials of IIT in the critically ill should stratify management and outcomes by premorbid diabetic status.

Augmented Renal Clearance in the Critically Ill: How to Assess Kidney Function

Objective:Intracranial pressure monitoring is standard of care after severe traumatic brain injury. Episodes of increased intracranial pressure are secondary injuries associated with poor outcome. We developed a model to predict increased intracranial pressure episodes 30 mins in advance, by using the dynamic characteristics of continuous intracranial pressure and mean arterial pressure monitoring. In addition, we hypothesized that performance of current models to predict long-term neurologic outcome could be substantially improved by adding dynamic characteristics of continuous intracranial pressure and mean arterial pressure monitoring during the first 24 hrs in the ICU. Design:Prognostic modeling. Noninterventional, observational, retrospective study. Setting and Patients:The Brain Monitoring with Information Technology dataset consisted of 264 traumatic brain injury patients admitted to 22 neuro-ICUs from 11 European countries. Interventions:None. Measurements:Predictive models were built with multivariate logistic regression and Gaussian processes, a machine learning technique. Predictive attributes were Corticosteroid Randomisation After Significant Head Injury-basic and International Mission for Prognosis and Clinical Trial design in TBI-core predictors, together with time-series summary statistics of minute-by-minute mean arterial pressure and intracranial pressure. Main Results:Increased intracranial pressure episodes could be predicted 30 mins ahead with good calibration (Hosmer-Lemeshow p value 0.12, calibration slope 1.02, calibration-in-the-large −0.02) and discrimination (area under the receiver operating curve = 0.87) on an external validation dataset. Models for prediction of poor neurologic outcome at six months (Glasgow Outcome Score 1–2) based only on static admission data had 0.72 area under the receiver operating curve; adding dynamic information of intracranial pressure and mean arterial pressure during the first 24 hrs increased performance to 0.90. Similarly, prediction of Glasgow Outcome Score 1–3 was improved from 0.68 to 0.87 when including dynamic information. Conclusion:The dynamic information in continuous mean arterial pressure and intracranial pressure monitoring allows to accurately predict increased intracranial pressure in the neuro-ICU. Adding information of the first 24 hrs of intracranial pressure and mean arterial pressure monitoring to known baseline risk factors allows very accurate prediction of long-term neurologic outcome at 6 months.

Reduced nocturnal ACTH-driven cortisol secretion during critical illness

BACKGROUND: Augmented renal clearance in critically ill patients can result in underdosing of life-saving drugs, potentially leading to therapeutic failure. To detect this phenomenon, correct assessment of the kidney function is essential. Currently, little is known about the validity of mathematical formulas to estimate renal function in this subset of patients. OBJECTIVE: To evaluate the validity of different methods to estimate kidney function in critically ill patients with augmented renal clearance by comparing measured renal clearance with estimated clearance using different formulas. METHODS: An observational, retrospective, single-center study was conducted in a 34-bed surgical intensive care unit (SICU) of the University Hospitals Leuven, Leuven, Belgium. Adults admitted to the SICU in 2010 with a measured creatinine clearance (CrCl) of 120 mL/min or more (based on 24-hour urinary collection) were included. The measured clearance values were compared with estimated clearance values as calculated by the Cockcroft-Gault (CrClCG) method and the re-expressed 4-variable Modification of Diet in Renal Disease estimated glomerular filtration rate (eGFR) formula. Spearman rank order correlation was performed to determine the relationship between measured and estimated clearances. Bland-Altman plots were evaluated to assess bias and limits of agreement between the 2 methods. RESULTS: Records on 1317 patients were screened. Augmented renal clearance was present in 390 patients. Spearman correlation showed fair correlation between measured and estimated clearances (rs = 0.343; p < 0.001 [CrClCG] and rs = 0.290; p < 0.001 [eGFR]). Bias was −11.2 mL/min with limits of agreement (–131.7; 109.3 mL/min [CrClCG]) and −19.9 mL/min with limits of agreement (–170.4; 130.7 mL/min [eGFR]). CONCLUSIONS: Estimated renal clearances, such as the eGFR estimated by the MDRD formula or CrCl estimated by CG, showed poor agreement with measured CrCl values in our critically ill population displaying augmented renal clearance. Clinicians should be cautious when interpreting kidney function based on estimating equations in this subset of patients. Instead, measured CrCl using urinary collection is recommended in patients suspected of displaying augmented renal clearance.

Glucose Variability and Mortality in Patients Hospitalized With Acute Myocardial Infarction

Recently, during critical illness, cortisol metabolism was found to be reduced. We hypothesize that such reduced cortisol breakdown may suppress pulsatile ACTH and cortisol secretion via feedback inhibition. To test this hypothesis, nocturnal ACTH and cortisol secretory profiles were constructed by deconvolution analysis from plasma concentration time series in 40 matched critically ill patients and eight healthy controls, excluding diseases or drugs that affect the hypothalamic-pituitary-adrenal axis. Blood was sampled every 10 min between 2100 and 0600 to quantify plasma concentrations of ACTH and (free) cortisol. Approximate entropy, an estimation of process irregularity, cross-approximate entropy, a measure of ACTH-cortisol asynchrony, and ACTH-cortisol dose-response relationships were calculated. Total and free plasma cortisol concentrations were higher at all times in patients than in controls (all P < 0.04). Pulsatile cortisol secretion was 54% lower in patients than in controls (P = 0.005), explained by reduced cortisol burst mass (P = 0.03), whereas cortisol pulse frequency (P = 0.35) and nonpulsatile cortisol secretion (P = 0.80) were unaltered. Pulsatile ACTH secretion was 31% lower in patients than in controls (P = 0.03), again explained by a lower ACTH burst mass (P = 0.02), whereas ACTH pulse frequency (P = 0.50) and nonpulsatile ACTH secretion (P = 0.80) were unchanged. ACTH-cortisol dose response estimates were similar in patients and controls. ACTH and cortisol approximate entropy were higher in patients (P ≤ 0.03), as was ACTH-cortisol cross-approximate entropy (P ≤ 0.001). We conclude that hypercortisolism during critical illness coincided with suppressed pulsatile ACTH and cortisol secretion and a normal ACTH-cortisol dose response. Increased irregularity and asynchrony of the ACTH and cortisol time series supported non-ACTH-dependent mechanisms driving hypercortisolism during critical illness.