Effect of Flumazenil on Hypoactive Delirium in the ICU: A Double-Blind, Placebo-Controlled Pilot Study.

To determine whether the use of flumazenil reverses hypoactive delirium and increases delirium-free days in critically ill patients who were exposed to benzodiazepine therapy during the ICU admission. DESIGN: This was a single-center, double-blinded, randomized placebo-controlled pilot study. SETTING: Adult ICUs at a large academic medical center in the United States. PATIENTS: Adult, critically ill patients with benzodiazepine exposure and hypoactive delirium based on the Confusion Assessment Method-ICU and Richmond Agitation Sedation Scale assessments were considered for enrollment. INTERVENTIONS: Patients received a test dose of flumazenil starting at 0.1 mg intravenously and titrated up every 5 minutes by 0.1 mg increments up to a maximum total dose of 2 mg. Patients who demonstrated a Richmond Agitation Sedation Scale score increase of greater than 1 point were considered responders and randomized to flumazenil (0.05-0.3 mg/hr) or placebo infusion for up to 72 hours. Confusion Assessment Method-ICU scores were assessed twice daily for resolution of delirium. MEASUREMENTS AND MAIN RESULTS: The trial was stopped early based on the observed size effect and power analysis. Twenty-two of the 25 patients responded to the flumazenil test dose (88%). The median number of delirium-free days alive without coma within 14 days of enrollment was similar between the two infusion groups (12.7 vs 9.2; p = 0.19). There was no difference in the probability of delirium resolution within the first 14 days with 90% versus 70% in the flumazenil and placebo groups, respectively (p = 0.2). There was no statistical difference (odds ratio, 0.17; 95% CI, 0.022-1.23; p = 0.079) in delirium- and coma-free days at the end of the study drug infusion. There was no difference between groups in ICU length of stay (7.8 ± 4.8 vs 7 ± 8; p = 0.74). No serious adverse events occurred. CONCLUSIONS: This study found that flumazenil test dose and infusion present a potential option for hypoactive delirium associated with benzodiazepine exposure; however, the possible benefit is unknown. Larger studies are warranted to further evaluate these findings.

Comparison of Self-Reported and Behavioral Pain Assessment Tools in Critically Ill Patients.

BACKGROUND: Self-reported and behavioral pain assessment scales are often used interchangeably in critically ill patients due to fluctuations in mental status. The correlation between scales is not well elucidated. The purpose of this study was to describe the correlation between self-reported and behavioral pain scores in critically ill patients. METHODS: Pain was assessed using behavioral and self-reported pain assessment tools. Behavioral pain tools included Critical Care Pain Observation Tool (CPOT) and Behavioral Pain Scale (BPS). Self-reported pain tools included Numeric Rating Scale (NRS) and Wong-Baker Faces Pain Scales. Delirium was assessed using the confusion assessment method for the intensive care unit. Patient preference regarding pain assessment method was queried. Correlation between scores was evaluated. RESULTS: A total of 115 patients were included: 67 patients were nondelirious and 48 patients were delirious. The overall correlation between self-reported (NRS) and behavioral (CPOT) pain scales was poor (0.30, P = .018). In patients without delirium, a strong correlation was found between the 2 behavioral pain scales (0.94, P < .0001) and 2 self-reported pain scales (0.77, P < .0001). Self-reported pain scale (NRS) and behavioral pain scale (CPOT) were poorly correlated with each other (0.28, P = .021). In patients with delirium, there was a strong correlation between behavioral pain scales (0.86, P < .0001) and a moderate correlation between self-reported pain scales (0.69, P < .0001). There was no apparent correlation between self-reported (NRS) and behavioral pain scales (CPOT) in patients with delirium (0.23, P = .12). Most participants preferred self-reported pain assessment. CONCLUSION: Self-reported pain scales and behavioral pain scales cannot be used interchangeably. Current validated behavioral pain scales may not accurately reflect self-reported pain in critically ill patients.

Endurance capacity and high-intensity exercise performance responses to a high fat diet.

The effects of adaptation to a high-fat diet on endurance performance are equivocal, and there is little data regarding the effects on high-intensity exercise performance. This study examined the effects of a high-fat/moderate protein diet on submaximal, maximal, and supramaximal performance. Twenty non-highly trained men were assigned to either a high-fat/moderate protein (HFMP; 61% fat diet) (n = 12) or a control (C; 25% fat) group (n = 8). A maximal oxygen consumption test, two 30-s Wingate anaerobic tests, and a 45-min timed ride were performed before and after 6 weeks of diet and training. Body mass decreased significantly (-2.2 kg; p < or = .05) in HFMP subjects. Maximal oxygen consumption significantly decreased in the HFMP group (3.5 +/- 0.14 to 3.27 +/- 0.09 L x min(-1)) but was unaffected when corrected for body mass. Perceived exertion was significantly higher during this test in the HFMP group. Main time effects indicated that peak and mean power decreased significantly during bout 1 of the Wingate sprints in the HFMP (-10 and -20%, respectively) group but not the C (-8 and -16%, respectively) group. Only peak power was lower during bout 1 in the HFMP group when corrected for body mass. Despite significantly reduced RER values in the HFMP group during the 45-min cycling bout, work output was significantly decreased (-18%). Adaptation to a 6-week HFMP diet in non-highly trained men resulted in increased fat oxidation during exercise and small decrements in peak power output and endurance performance. These deleterious effects on exercise performance may be accounted for in part by a reduction in body mass and/or increased ratings of perceived exertion.

A ketogenic diet favorably affects serum biomarkers for cardiovascular disease in normal-weight men.

Very low-carbohydrate (ketogenic) diets are popular yet little is known regarding the effects on serum biomarkers for cardiovascular disease (CVD). This study examined the effects of a 6-wk ketogenic diet on fasting and postprandial serum biomarkers in 20 normal-weight, normolipidemic men. Twelve men switched from their habitual diet (17% protein, 47% carbohydrate and 32% fat) to a ketogenic diet (30% protein, 8% carbohydrate and 61% fat) and eight control subjects consumed their habitual diet for 6 wk. Fasting blood lipids, insulin, LDL particle size, oxidized LDL and postprandial triacylglycerol (TAG) and insulin responses to a fat-rich meal were determined before and after treatment. There were significant decreases in fasting serum TAG (-33%), postprandial lipemia after a fat-rich meal (-29%), and fasting serum insulin concentrations (-34%) after men consumed the ketogenic diet. Fasting serum total and LDL cholesterol and oxidized LDL were unaffected and HDL cholesterol tended to increase with the ketogenic diet (+11.5%; P = 0.066). In subjects with a predominance of small LDL particles pattern B, there were significant increases in mean and peak LDL particle diameter and the percentage of LDL-1 after the ketogenic diet. There were no significant changes in blood lipids in the control group. To our knowledge this is the first study to document the effects of a ketogenic diet on fasting and postprandial CVD biomarkers independent of weight loss. The results suggest that a short-term ketogenic diet does not have a deleterious effect on CVD risk profile and may improve the lipid disorders characteristic of atherogenic dyslipidemia.

Body composition and hormonal responses to a carbohydrate-restricted diet.

The few studies that have examined body composition after a carbohydrate-restricted diet have reported enhanced fat loss and preservation of lean body mass in obese individuals. The role of hormones in mediating this response is unclear. We examined the effects of a 6-week carbohydrate-restricted diet on total and regional body composition and the relationships with fasting hormone concentrations. Twelve healthy normal-weight men switched from their habitual diet (48% carbohydrate) to a carbohydrate-restricted diet (8% carbohydrate) for 6 weeks and 8 men served as controls, consuming their normal diet. Subjects were encouraged to consume adequate dietary energy to maintain body mass during the intervention. Total and regional body composition and fasting blood samples were assessed at weeks 0, 3, and 6 of the experimental period. Fat mass was significantly (P

Comparison of methods for assessing body composition changes during weight loss.

PURPOSE: Four cross-sectional studies have reported that percent body fat (%BF) measured by dual-energy x-ray absorptiometry (DXA) is significantly higher compared with values obtained with air displacement plethysmography (ADP) using the Bod Pod(R) in normal-weight individuals. This study was performed to confirm these findings in an overweight population and to assess whether DXA and ADP detected similar changes in body composition after moderate weight loss. METHODS: Twelve women (42 +/- 8 yr) and 10 men (40 +/- 11 yr) had their %BF, fat mass (FM), and fat-free mass (FFM) measured using DXA and ADP before and after an 8-wk weight-loss program involving moderate energy restriction and exercise. RESULTS: Body weight decreased significantly in women (-4.3 +/- 3.4 kg) and men (-4.7 +/- 3.1 kg). There were significant method (ADP vs DXA) and time (pre and post) effects but no method by time or gender interactions. Methods were significantly different in estimating %BF, FM, and FFM with ADP estimates of %BF and FM being lower and estimates of FFM higher than corresponding DXA values (P = 0.000). There were significant correlations accounting for a high degree of the shared variance between DXA and ADP (r = 0.98 to 0.99) for %BF, FM, and FFM and lower correlations for the changes in %BF (r = 0.66), FM (r = 0.86), and FFM (r = 0.34). In response to weight loss, the mean changes in %BF, FM, and FFM were not significantly different between methods (P > 0.05). CONCLUSION: Both DXA and ADP measure changes in body composition after small to moderate weight loss to the same extent and with similar sensitivity.