Combining the strength-duration curve of the external anal sphincter with manometry for the assessment of faecal incontinence.

BACKGROUND: The strength-duration curve of a muscle is thought to be a measure of its innervation. This study was designed to evaluate the ability of the strength-duration curve of the external anal sphincter to discriminate between controls and patients with faecal incontinence. METHODS: Forty-three women with faecal incontinence due to sphincter weakness were studied together with 45 age-matched women with no disorders of defaecation. Strength-duration curves of the external anal sphincter and anorectal manometry were recorded for all subjects with the additional measurement of pudendal nerve terminal motor latency in the incontinent group. RESULTS: Logistic regression was performed using resting and voluntary squeeze pressures and current strengths at 28 different pulse durations to develop a predictive equation for incontinence. Only currents at 1 and 6 ms were significant predictors. When anorectal manometry data were included, only the current required to elicit contraction at 1 ms was necessary. The following regression equation can be applied to predict continence in this population with a sensitivity of 95 per cent and a specificity of 100 per cent: logit(P)=4.1605-(0.0559 x squeeze pressure)-(0.1755 x resting pressure)+0.8622I(1 ms). A negative value indicates continence. CONCLUSION: The strength-duration curve, when used in conjunction with anorectal manometry, may have a role in the investigation of faecal incontinence.

Effect of a chimeric antibody to tumor necrosis factor-alpha on cytokine and physiologic responses in patients with severe sepsis--a randomized, clinical trial.

OBJECTIVES: Tumor necrosis factor (TNF)-alpha appears central to the pathogenesis of severe sepsis, but aspects of the cytokine cascade and the link to physiologic responses are poorly defined. We hypothesized that a monoclonal antibody to TNF-alpha given early in the course of severe sepsis would modify the pattern of systemic cytokine release and, as a consequence, resuscitation fluid requirements, net proteolysis, and hypermetabolism would be reduced. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: Critical Care Unit and University Department of Surgery in a single tertiary care center. PATIENTS: Fifty-six patients (from 92 eligible patients) with severe sepsis. Twenty-eight patients were randomized to treatment, and were comparable with the placebo group for age, gender, race, Acute Physiology and Chronic Health Evaluation II score, and site and type of infection. INTERVENTIONS: A 300-mg single dose of cA2 (a chimeric neutralizing antibody to TNF-alpha) was given intravenously within 12 hrs of the onset of severe sepsis. Standard surgical and intensive care therapy was otherwise delivered. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of TNF-alpha, interleukin (IL)-1beta IL-6, IL-8, IL-10, soluble 75-kilodalton TNF-alpha receptor (sTNFR-75), and IL-1beta receptor antagonist (IL-1ra) were measured by sandwich enzyme-linked immunosorbent assay before cA2 infusion, 8 hrs later, and then daily for a minimum of 4 days. Sequential changes in total body protein, body water spaces, and resting energy expenditure over 21 days were measured, as soon as patients achieved hemodynamic stability, by in vivo neutron activation analysis, tritium and bromide dilution, and indirect calorimetry, respectively. Twenty-one patients died, ten having received cA2. Suppression of measurable TNF-alpha was observed at 8 hrs with subsequent rebound by 24 hrs after cA2 treatment. The concentrations of other cytokines were high, were not reduced by intervention, and decreased logarithmically over 5 days. Both groups reached hemodynamic stability at similar times (57.5 +/- 11.8 hrs in controls vs. 58.6 +/- 9.2 hrs in the cA2 group) and following similar volumes of infused fluids (29.1 +/- 3.4 L vs. 28.9 +/- 4.4 L). No differences in net proteolysis, resolution of body water expansion, or alteration in resting energy expenditure were demonstrated. CONCLUSION: A single dose of cA2 did not alter the overall pattern of cytokine activation or the profound derangements in physiologic function that accompany severe sepsis.

Evaluation of multifrequency bioimpedance spectroscopy for measurement of the extracellular water space in critically ill patients.

The purpose of this study was to compare multifrequency bioimpedance spectroscopy (BIS) estimates of extracellular water volume (ECW) in critically ill patients with measurements by bromide dilution. Stable bromide dilution and BIS were performed in 37 critically ill patients as soon as haemodynamic stability was achieved (day 0) and again 10 days later. While BIS underestimated the dilution results on each day of measurement, the 10-day changes in ECW agreed closely for the two methods (4.42 +/- 4.25 (s.d.) vs 4.43 +/- 4.84 1).

Sequential changes in the metabolic response in critically injured patients during the first 25 days after blunt trauma.

BACKGROUND: Understanding the changes in energy expenditure and body composition is essential for the optimal management of the critically injured, yet these changes have not been quantified within the current context of trauma care. METHODS: Ten critically injured patients (median Injury Severity Score = 35) had measurements of energy expenditure and body composition as soon as they were hemodynamically stable and then every 5 days for 21 days. RESULTS: Resting energy expenditure rose to 55% above predicted and remained elevated throughout the study period. Total energy expenditure was 1.32 X resting energy expenditure. Body fat was oxidized when energy intake was insufficient (r=-0.830, p<0.02). Body water changes closely paralleled body weight changes and were largely accounted for by changes in extracellular water. Over the 21-day study period, there was a loss of 1.62 kg (16%) of total body protein (p<0.0002), of which 1.09 kg (67%) came from skeletal muscle. Intracellular potassium was low (133 +/- 3 mmol/L, p<0.02) but did not deteriorate further after hemodynamic stability had been reached. CONCLUSIONS: These results show that the period of hypermetabolism lasts longer and the protein loss is greater in critically injured patients than previously thought. Most, but not all, the protein is lost from muscle. Fat loss can be prevented and cell composition preserved once hemodynamic stability is achieved.

Body composition studies in intensive care patients: comparison of methods of measuring total body water.

Changes in total body water (TBW) were monitored in 12 critically-ill intensive care patients using four independent methods. Over the 10-day study period TBW measured by tritium dilution changed from 51.3 ± 2.5 (SEM) kg to 43.6 ± 2.3 kg, an average loss of 7.7 ± 0.8 kg. A six-compartment model of the body incorporating measurements of protein by in vivo neutron activation analysis and fat and bone mineral by dual-energy X-ray absorptiometry was used to determine TBW by difference from body weight. The 10-day change in TBW measured by this approach was 8.4 ± 0.9 kg which correlated well with the tritium dilution changes (r=0.84, P<0.01, SEE=1.83 kg). The changes measured by single frequency and multi-frequency bio- electrical impedance analysis were not significantly different from the tritium results (9.7 ± 1.3 and 8.2 ± 0.8 kg. respectively) although the prediction errors were high for both methods (SEE=3.29 and 2.72 kg, respectively) with correlations that were statistically significant for the single frequency approach but not for the multi-frequency approach (r=0.71, P<0.01 and r=0.45, ns, respectively). The high prediction errors render these impedance techniques inappropriate, at the present time, for monitoring total water changes in individual intensive care patients.

A new method for the estimation of the components of energy expenditure in patients with major trauma.

The management of critically ill patients would be better understood if the total energy expenditure (TEE) and its components are known. To quantify the different components of energy expenditure in patients with major trauma, we used a technique combining measurements of body composition and oxygen consumption. We determined changes in body weight, total body water, total body protein, total body potassium, total body fat, and bone mineral content every 5 days over a 10-day period in a group of nine multiply injured patients. Resting energy expenditure was measured by indirect calorimetry (REEm), and a predicted value was obtained from total body potassium (REEp). TEE was assessed by adding the total calorie intake to the changes in body energy stores, and the activity energy expenditure (AEE) was calculated by subtracting REEm from TEE. Mean daily values for REEm, REEp, TEE, and AEE were 2,236 +/- 140, 1,683 +/- 82, 3,029 +/- 276, and 793 +/- 213 kcal/day, respectively, over the 10-day study period. Although not statistically significant, the mean AEE was four times smaller for the first 5 days of study than for the second 5 days (298 +/- 400 vs. 1,254 +/- 588 kcal/day). The technique of combining indirect calorimetry and body composition measurements offers a new approach to evaluate energy expenditure and a new way to study metabolic disorders and therapeutic strategies in critically ill patients.