Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation

Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation

Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation Meritxell Girvent, MD, Syl...

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Euthyroid sick syndrome, associated endocrine abnormalities, and outcome in elderly patients undergoing emergency operation Meritxell Girvent, MD, Sylvia Maestro, MD, Raquel Hernández, MD, Isabel Carajol, MD, Josep Monné, MD, Joan J. Sancho, MD, J. M. Gubern, MD, and Antonio Sitges-Serra, MD, FRCSEd, Barcelona, Spain

Background. Emergency operation in the elderly carries a high risk of death. We investigated the incidence of euthyroid sick syndrome (ESS) and associated nutritional and endocrine abnormalities and their relationship to postoperative outcome in this population. Methods. Sixty-six patients older than 70 years of age requiring emergency operations were assessed before any therapeutic intervention. Values for thyroid hormones, catecholamines, cortisol, interleukin-6, interleukin-1, C-reactive protein, and the Acute Physiology and Chronic Health Evaluation II score were determined. Nutritional assessment was carried out. Mortality rates and duration of hospital stay were related to ESS and albumin concentrations. Results. ESS was diagnosed in 34 patients (51.50%) and was associated with worse Acute Physiology and Chronic Health Evaluation II scores (10.9 vs 8.6; p = 0.004), hypoalbuminemia (34.7 vs 40.8 gm/L; p = 0.0001), lower triceps skinfold (11.8 vs 14.6 mm; p = 0.03), and higher cortisol and norepinephrine levels (937 vs 741 nmol/L [p = 0.04] and 358 vs 250 pg/ml [p = 0.02], respectively), interleukin-6 plasma concentrations (347 vs 113 pg/ml; p = 0.01), death rate (20% vs 0%; p = 0.02), and length of hospital stay (17.2 vs 11.8 days; p = 0.03). A serum albumin level less than 35 gm/L was virtually always associated with ESS. Conclusions. ESS is highly prevalent in the elderly with acute surgical problems and is associated with poor nutrition, higher sympathetic response, and worse postoperative outcome. The serum albumin level at admission is a specific marker of ESS. (Surgery 1998;123:560-7.) From the Department of Surgery, Hospital Universitari del Mar, the Immunology Unit, Hospitals de la Vall d’Hebró, and Cetir Laboratories, Barcelona, Spain

AS THE ELDERLY POPULATION INCREASES in western societies, so is the number of emergency surgical procedures carried out in this high-risk group of patients. Urgent operations in older patients (70+ years) carry high mortality and morbidity rates.1,2 Factors relevant for this poor outcome are concomitant illnesses and malnutrition.2-4 These have been associated with low circulating triiodothyronine (T3) levels in the context of the so-called euthyroid sick syndrome (ESS), which may reflect Supported by grants 123/92 from the Comisión Interministerial de Ciencia y Tecnología and 95/0326 from the Fondo de Investigaciones Sanitarias, Ministry of Health, Spain. Accepted for publication Oct. 22, 1997. Reprint requests: Antonio Sitges-Serra, MD, Department of Surgery, Hospital Universitari del Mar, P. Maritim, 25-29, 08003 Barcelona, Spain. Copyright © 1998 by Mosby, Inc. 0039-6060/98/$5.00 + 0 11/56/87238

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a poor neuroendocrine adaptation to stress and has an adverse effect on clinical outcome.5,6 ESS is defined as a low circulating T3 level with a reciprocal increase in reverse T3 (rT3) level, the inactive metabolite of thyroxine, in patients with nonthyroidal illness. An impaired peripheral deiodination of thyroxine (T4) by type 1 deiodinase seems to be the main reason for the decreased plasma concentration of T3.7 The pathogenesis of ESS is unclear. Starvation, infections, and trauma have been associated with ESS, although the mechanisms whereby these clinical entities impair the peripheral deiodination of T4 are obscure.7 Recently it has been suggested that several cytokines, mainly interleukin (IL)-6, tumor necrosis factor–α, and interferon-α, may mediate the inhibition of the 5´-deiodinase in stressful conditions.8-11 Hypoalbuminemia is an excellent predictor of morbidity and death in surgical patients12,13 and

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Fig. 2. Correlation between rT3 and CRP values. Fig. 1. Correlation between T3/rT3 ratio and serum albumin levels at admission for entire series of patients.

Table I. Diagnosis at admission in a consecutive series of 66 elderly patients with acute surgical conditions Condition

No.

Long bone fractures 39 Femur 35 Humerus 3 Radius 1 Localized peritonitis 8 Diffuse peritonitis 2 Upper gastrointestinal bleeding 2 Bowel obstruction (not complicated 9 with infection) Bowel obstruction (complicated with infection) 2 Severe soft tissue infections 1 Bowel infarction 1 Acute ischemia of lower limbs 2

also in the elderly with different medical conditions.14 No data are available, however, on the usefulness of albumin levels as a risk marker in the elderly undergoing emergency operations or its value as a potential marker of ESS. This study was set up with the following aims: (1) to investigate the prevalence of ESS in an elderly population about to undergo an emergency surgical procedure; (2) to correlate ESS with the severity of the disease by objective and subjective assessment; (3) to define other nutritional, endocrine, and interleukin abnormalities associated with ESS; (4) to elucidate whether ESS is associated with hypoalbuminemia; and (5) to establish a relationship between ESS, the length of hospital stay, and the death rate. PATIENTS AND METHODS Patients older than 70 years of age, consecutively admitted for acute surgical conditions to the emergency department of the Hospital Universitari del

Fig. 3. Close correlation between serum levels of IL-6 at admission and APACHE II scores in patients with ongoing sepsis.

Mar under the care of one of us (M.G.), were prospectively investigated. Patients were included if a surgical procedure or an aggressive diagnostictherapeutic intervention was planned within 1 week after admission. Excluded were patients with a medical history of thyroid disease and those taking thyroid-replacement therapy or drugs known to influence thyroid hormone levels (steroids, amiodarone, aspirin, antidepressants, phenobarbital, β-blockers, dopamine, heparin, or estrogens). Patients were studied and blood was sampled at the time of emergency admission before any treatment was started. Before entering the study, thorough information about the nature and aims of the investigation was given and written consent was obtained from the patient or the next of kin. A venous line was inserted and anamnesis and nutritional assessment were carried out. At least 30 minutes after line insertion, with the patient lying in bed and before any other invasive technique was performed, 30 ml blood was drawn. Plasma was centrifuged, divided in aliquots, and stored at –21° C for further determination of albumin, prealbu-

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Table II. Metabolic assessment of 66 elderly patients at the time of admission with acute surgical conditions Mean (95% CI) Age (yr) Hospital stay (days)* No. of deaths Serum albumin (gm/L) Prealbumin (mg/dl) Retinol binding protein (mg/dl) Grip strength (kg) Triceps skinfold (mm) APACHE II score TSH (µU/ml) T4 (nmol/L) Free T4 (nmol/L) T3 (nmol/L) rT3 (ng/ml) T3/rT3 Norepinephrine (pg/ml) Epinephrine (pg/ml) Dopamine (pg/ml) Cortisol (nmol/L) IL-1 (pg/ml)† IL-6 (pg/ml) CRP (mg/dl)

81 (79-82) 15 (12.6-17.7) 7/66 (10.2%) 37 (36-39) 17.4 (16-19) 3.7 (3.3-4.1) 10.5 (9-12) 13.2 (11.9-14.6) 9.8 (9-10.7) 1.28 (0.99-1.57) 97.5 (90.8-104) 14.8 (13.6-16) 1.16 (1-1.27) 0.41 (0.35-0.47) 3.87 (3.2-4.5) 306 (260-352) 61 (49-74) 38 (26.6-49.3) 836 (737-934) <1.9 (in 63/66 cases) 234 (109-359) 3.07 (2.01-4.12)

Reference values

35-51 17-41 2.5-8 18 (adjusted for gender mix) 0.5-4 58-161 10-25 1.08-3.08 0.09-0.35 >3 185-275 30-85 30-85 194-745 <3-8.5 <1.1

CI, Confidence interval; TSH, thyroid-stimulating hormone. *Excluding deaths. †Levels

above the sensitivity of the assay detected in three patients only.

Table III. Biochemical and physiologic markers in 66 elderly surgical patients with (n = 34) or without (n = 32) ESS Patients with ESS Age (yr) Hemoglobin (gm/dl) Creatinine (mg/dl) Na (mEq/L) Rectal temperature (° C) Systolic BP (mm Hg) Diastolic BP (mm Hg) Heart rate (beats/min) Respiratory rate (beats/min) APACHE II ASA classification Hospital stay (days)* No. deaths

82 (77.8-88) 12.6 (11.7-13.5) 1.2 (1-1.44) 136 (134-138) 37.5 (37.2-37.7) 142 (133-152) 73 (67-79) 82 (77-86) 24 (22-26) 10.9 (9.7-12.2) II, 36%; III, 59%; IV, 17% 17.2 (12.8-21.5) 7/34 (20.6%)

Patients without ESS 80 (77-83) 13.6 (12.9-14) 0.9 (0.8-1) 139 (138-140) 37.2(37.1-37.4 153 (144-162) 86 (81-91) 82 (78-85) 20 (18-21) 8.6 (7.7-9.5) II, 63%; III, 40%; IV, 0% 11.8 (9.7-13.9 0/32 (0%)

p Value NS NS (0.08) 0.008 0.001 NS NS (0.09) 0.001 NS 0.001 0.004 0.01 0.03 0.02

Numbers in parentheses indicate 95% confidence interval. NS, Statistically not significant; BP, blood pressure. *Excluding deaths.

min, retinol-binding protein, thyroid hormones, fractionated catecholamines, cortisol, IL-6, and IL1. A basic analytic profile including blood gas analysis was also performed. The Acute Physiology and Chronic Health Evaluation (APACHE) II severity score was calculated.15 Hormones, C-reactive protein (CRP), and interleukin measurements. Thyroid-stimulating hor-

mone, total T4, free T4, total T3, and rT3 were determined by radioimmunoassay (Diagnostics Production Corp., Behring, Düsseldorf, Germany). A ratio of T3/rT3 of less than 3 was used to define the presence of ESS. Determination of fractionated plasma catecholamine levels (epinephrine, norepinephrine, and dopamine) was performed by highresolution chromatography. Plasma cortisol levels

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Table IV. Endocrine, nutritional, and inflammatory markers in 66 elderly surgical patients with (n = 34) or without (n = 32) ESS TSH (µU/ml) T3 (nmol/L) rT3 (ng/ml) T4 (nmol/L) Free T4 (nmol/L) Norepinephrine (pg/ml) Epinephrine (pg/ml) Dopamine (pg/ml) Cortisol (nmol/L) Lymphocytes (mm3) IL-6 (pg/ml) CRP (mg/dl) Grip strength (kg) Triceps skinfold (mm) Serum albumin (gm/L) Prealbumin (mg/dl) Retinol binding protein (mg/dl)

Patients with ESS

Patients without ESS

p Value

1.4 (1.01-1.7) 0.86 (0.7-1) 0.55 (0.45-0.65) 95 (84-105) 15.5 (13.5-17.4) 358 (283-433) 66 (45-86) 45 (26-64) 937 (782-1092) 979 (782-1176) 347 (106-588) 4.89 (3.2-6.5) 8.5 (6.3-10.8) 11.8 (10.1-13.5) 34.7 (32.6-36.7) 14.5 (12.6-16.3) 3.3 (2.8-3.8)

1.6 (0.7-1.6) 1.4 (1.3-1.6) 0.25 (0.23-0.28) 99 (91-108) 14 (12.7-15.3) 250 (199-302) 56 (41-72) 30 (17-43) 741 (619-864) 1109 (916-1302) 113 (93-132) 1.18 (0.23-2.31) 12.7 (10.8-14.5) 14.7 (12.6-16.7) 40.8 (39.7-41.9) 20.6 (18.8-22.4) 4.2 (3.6-4.7)

NS 0.0001 0.0001 NS NS 0.02 NS NS 0.04 NS 0.01 0.0002 0.006 0.03 0.0001 0.0001 0.01

Numbers in parentheses indicate 95% confidence interval. TSH, Thyroid-stimulating hormone; NS, not significant.

were measured by radioimmunoassay. CRP was determined by immunonephelometry (Array 360 system; Beckman). IL-l-β was measured by enzymelinked immunosorbent assay (Biotrack, RPN 2141; Amersham Corp.), which can detect plasma levels above 3.9 pg/ml. IL-6 was determined by enzymelinked immunosorbent assay (4012600 Medgénix). Nutritional assessment. The triceps skinfold was measured three times with a caliper (Holtain LTD, Crymych, U.K.), and the mean value was obtained. Hand-grip strength of the nondominant forearm was measured three times with a dynamometer after the patients were instructed appropriately. The mean value was obtained and expressed in kilograms. All anthropometric and dynamometric measurements were carried out by the same investigator (M.G.). A triceps skinfold measurement below the 50th percentile for the age-adjusted Spanish population16 was used as the cutoff for defining marasmic malnutrition. In-hospital follow-up. After initial assessment, the patients were left under the care of the attending surgeon. The American Society of Anesthesiology (ASA) score was recorded. Patients were followed up during their hospital stay until death or discharge. The final diagnosis, type of surgical procedure, presence or absence of infection at admission, and length of hospital stay for surviving patients were recorded. Statistical analysis. Sample size was calculated on the basis that about 40% to 60% of patients included would have ESS, and this would result in a mortality rate between 10% and 20%.6 Thus we aimed

at including between 60 and 70 patients to allow comparisons between groups of about 30 subjects each with a type II error below 10% when variables differing by less than 20% were compared. Comparison between means was assessed by a twotailed, unpaired Student t test or analysis of variance test. When data were not distributed normally, comparisons were made with the Mann-Whitney U test. The chi-squared test, or Fisher’s exact test when appropriate, was used to determine the significance when proportions were compared. The Spearman correlation coefficient (r) was calculated to assess the correlation between variables. All data were filed on an information data sheet (FileMaker Pro 2.0; Claris Corp.) and then exported to the statistical package Statview 2.0 (Abacus Concepts Inc., Berkeley, Calif.). Data processing was done with a Macintosh LCII (Apple Computer Inc., Cupertino, Calif.). The results are expressed as means (95% confidence intervals) or, for analysis of variance tests, means ± SD. Statistical significance was set at p < 0.05. RESULTS Sixty-six patients were included in the study. There were 16 men and 50 women with a mean age of 81 years (range, 79 to 82 years). The diagnoses at admission are shown in Table I. The initial clinical, nutritional, and endocrine assessments for the entire series are shown in Table II. ESS was diagnosed in 34 patients (51.5%), hypoalbuminemia in 15 (23%), and a low triceps skinfold in 43 (65%).

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Table V. Preoperative values of thyroid hormones according to groups of ASA and APACHE II scores in 66 elderly patients admitted on an emergency basis

TSH (µU/ml) T4 (nmol/L) T3 (nmol/L) rT3 (ng/ml) T3/rT3 ESS (%)† IL-6 (pg/ml) APACHE II No. of deaths

ASA II (n = 33)

ASA III (n = 27)

1.2 ± 1.1 99 ± 26 1.3 ± 0.4 0.33 ± 0.1 4.4 ± 1.8 36 136 ± 156 8.4 ± 2.3 1/33 (3%)

1.1 ± 0.7 99 ± 28 1.1 ± 0.5 0.4 ± 0.3 3.8 ± 3.4 57 192 ± 175 10.7 ± 3 3/27 (11%)

ASA IV (n = 6) 2.35 ± 1.9 77 ± 24 0.59 ± 0.2 0.62 ± 0.4 1.33 ± 0.9 100 311 ± 378 13.6 ± 3.5 3/6 (50%)

p Value 0.05 NS 0.0001 0.007 0.02 0.01 NS 0.0001 0.002

TSH, thyroid-stimulating hormone; NS, not significant. *Cutoffs based on the frequency distribution of the APACHE II score in the sample. †Percentage

of patients with ESS (T3/rT3 < 3).

Sixteen patients (24%) had infection at the time of admission. Seven patients (10.6%) died during hospital admission. A comparison of metabolic, nutritional, endocrine, and immunologic profiles of patients with or without ESS is presented in Tables III and IV. All markers were worse in patients with a low T3/rT3 ratio, and all seven deaths occurred in the group with ESS. For the entire series, significant correlations were obtained between the T3/rT3 ratio and preoperative serum albumin (r = 0.54; p = 0.001; Fig. 1), prealbumin (r = 0.56; p = 0.0001), and CRP values (r = 0.57; p = 0.0001). Correlation between T3/rT3 and IL-6 was poor (r = 0.37; p = 0.003). Correlations were slightly better for rT3 alone: albumin (r = –0.55; p = 0.0001), prealbumin (r = –0.66; p = 0.0001), CRP (r = 0.75; p = 0.0001; Fig. 2), and IL-6 (r = 0.57; p = 0.0001). Thyroid hormone concentrations were compared according to the ASA and APACHE II scores of disease severity (Table V). There was good agreement between low T3 and high rT3 values and assessment of disease severity by the two methods. There were no significant differences in plasma fractionated catecholamine or cortisol levels between the different subgroups of disease severity. A similar analysis was carried out to identify the metabolic and endocrine derangements present in patients with hypoalbuminemia (Table VI). Their death rate was substantially higher, but the difference was not statistically significant. There was a weak correlation between albumin and IL-6 (r = 0.31; p = 0.01 ). IL-6 did not correlate with any other plasma protein including CRP. The presence of sepsis was associated with higher severity of disease and lower values for T3, T3/rT3, and albumin (Table VII). The prevalence of ESS was higher in patients with infections (81%

vs 42%; p = 0.01). Cortisol and inflammatory markers were higher in patients with infections. However, good correlations with thyroid hormones were observed only for CRP-rT3 (r = 0.68; p = 0.009) and CRP-T3/rT3 (r = 0.63; p = 0.01). IL-6 showed an excellent correlation with the APACHE II score (r = 0.84; p = 0.001; Fig. 3) in patients with infections at admission but not in patients without infections (r = 0.06). The death rate and length of stay for surviving patients were higher in patients with both ESS and hypoalbuminemia (Tables III and VI). There was a correlation between length of stay and serum albumin values at admission (r = 0.6; p = 0.0001). DISCUSSION A high prevalence of ESS was found in these elderly surgical patients, confirming previous findings in patients with medical emergencies.6 Chronic malnutrition has been implicated in the pathogenesis of ESS in elderly patients with acute medical problems,4,6 and both metabolic derangements have been independently associated with a poor outcome. In this study, patients with ESS had significantly lower serum concentrations of all plasma proteins and lower hand-grip strength and triceps skinfold measurements than had the group without ESS, suggesting preexisting malnutrition. Mean values for triceps skinfold in patients with ESS were around 40% below the standards for the Spanish population. The association of thin triceps skinfold with poor outcome in the elderly has been reported by Christou et al.13 and Bastow et al.17 in women with fractured femur, a common condition in our study. Low hand-grip strength has also been linked to malnutrition and has been reported to affect the outcome of surgical patients independently.18

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APACHE II * <8 (n = 19)

APACHE II 8-12 (n = 27)

APACHE II >12 (n = 15)

p Value

1.3 ± 1.4 95 ± 23 1.2 ± 0.2 31 ± 0.1 4.7 ± 2.5 42 117 ± 57 6.2 ± 0.6 1/19 (5%)

0.9 ± 0.6 97 ± 30 1.2 ± 0.4 0.37 ± 0.2 4 ± 2.2 41 125 ± 73 9.9 ± 0.8 2/22 (10%)

1.5 ± 1.3 96 ± 30 0.8 ± 0.3 0.6 ± 0.3 1.8 ± 1.5 93 301 ± 285 14 ± 1 3/15 (26%)

NS NS 0.002 0.002 0.0001 0.003 0.004 0.0001 NS

There is much interest in elucidating which mediators are involved in the impairment of peripheral T3 deiodination. Cortisol and the catecholamines have been implicated in the pathogenesis of ESS.19 In this study, however, no clear correlation could be established between these hormones and the thyronines or the T3/rT3 ratio. In fact, although ESS correlated well with the severity of disease, neither plasma cortisol nor catecholamine levels were elevated significantly in the more severely ill patients. Recently, emphasis has been given to IL-6 as a potential mediator of ESS. Corssmit et al.11 induced ESS in eight healthy volunteers by intravenous administration of interferon-α. The subjects had no change in plasma T4 levels, but a lowering effect was observed on both thyroid-stimulating hormone and T3 values, with a parallel increase in rT3 concentrations. There was a modest rise of IL-6 concentrations, and no changes were noted in tumor necrosis factor or IL1. Boelen et al.8 measured IL-6 and soluble cytokine (IL-1 and tumor necrosis factor–α) receptors in patients with ESS and noted a significant negative correlation (r = –0.56) between this cytokine and circulating T3 levels. In our population this correlation was substantially lower (r = –0.32) and did not improve when corrected for the T3/rT3 ratio or adjusted for the presence or absence of infection at admission. On the other hand, we found a tighter correlation between rT3 and IL-6. Thus it is not clear whether IL-6 is a mediator of ESS and whether its influence is more marked on type 3 deiodinase, resulting in increased levels of rT3, rather than inhibiting type 1 deiodinase, resulting in decreases in T3 levels. Whatever the intimate mechanisms leading to ESS, this study suggests that there is a close relation-

ship between the magnitude of the disturbance of thyroid hormone metabolism and the severity of the underlying disease. No other endocrine marker correlated as well with both subjective and objective assessments of severity of disease as the T3/rT3 ratio. This may be explained by the fact that ESS has its origin in a peripheral disturbance rather than a central endocrine organ (e.g., changes in cortisol, insulin, or catecholamine levels); a low T3/rT3 ratio would be a marker of diffuse parenchymal injury and, secondarily, impending organ dysfunction. Thus a low T3 status may represent a “functional” peripherally originated hypothyroidism. Others regard ESS associated with acute illness as an adaptative mechanism aimed at reducing the metabolic demands, sparing nitrogen. Teleologically, this would imply that the body economy might sacrifice the cardiovascular and thermogenic actions of T3—provisionally substituted by an increased sympathetic tone—to eliminate any further catabolic drive. Boelen et al.8 have suggested that the inverse correlation between T3 and IL-6 may indicate an activation of the antiinflammatory actions of this cytokine in stress and would further support the adaptative role of the low T3 syndrome. This, however, remains controversial. Rising serum T3 concentrations in patients undergoing coronary artery bypass increases cardiac output and lowers systemic vascular resistance but does not change outcome or alter the need for standard postoperative therapy.20 Currently most authorities are cautious in interpreting the functional consequences of ESS and in recommending thyroid hormone supplementalion in ESS.7,21 Because thyroid hormone analysis cannot be performed routinely at admission to the hospital, the relationship between ESS and hypoalbuminemia was investigated. We found a substantial over-

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Table VI. Endocrine, nutritional, and inflammatory markers in 66 elderly surgical patients with (n = 15) or without (n = 51) hypoalbuminemia (serum albumin < 35 gm/L) Serum albumin < 35 gm/L Hemoglobin (gm/dl) Prothrombin time (%) Creatinine (mg/dl) Systolic BP (mm Hg) Dyastolic BP (mm Hg) Respiratory rate (beats/min) APACHE II TSH (µU/ml) T3 (nmol/L) rT3 (ng/ml) T4 (nmol/L) T3/rT3 ESS (%) Norepinephrine (pg/ml) IL-6 (pg/ml) CRP (mg/dl) Grip strength (kg) Triceps skinfold (mm) Serum albumin (gm/L) Prealbumin (mg/dl) Hospital stay (days) No. of deaths†

11.6 (10.2-13) 77 (70-85) 1.3 (0.9-1.6) 131 (118-144) 68 (60-77) 26 (22-29) 12.2 (10.3-14) 1.6 (0.8-2.4) 0.73(0.54-0.93) 0.58 (0.44-0.73) 82 (63-100) 1.5 (0.95-2) 93 395 (254-536) 509 (24-1043) 6.2 (3.4-9) 7.2 (4.3-10) 12.7 (10-15.4) 29.2 (27.2-31.1) 11.1 (9.3-13) 21.4 (12.4-30.3) 3/15 (20%)

Serum albumin > 35 gm/L 13.4 (12.9-14) 90 (86-94) 1 (0.8-1.1) 152 (145-160) 83 (78-87) 20 (19-22) 9.1 (8.3-9.9) l.l (0.87-1.4) 1.2 (1.1-1.4) 0.36 (0.29-0.42) 102 (95-108) 4.5 (3.8-5.3) 40 279 (234-324) 150 (99-201) 2.2 (1.2-3.2) 11.5 (9.7-13.2) 13.4 (11.8-15) 40.1 (39.3-41) 19.3 (17.8-20.8) 12.6 (10.6-14.6) 4/47 (8%)

p Value* 0.004 0.004 0.04 0.005 0.002 0.001 0.001 NS (0.1) 0.0001 0.002 0.01 0.0001 0.0007 0.03 0.01 0.001 0.01 NS 0.0001 0.0001 0.002 NS (0.2)

Numbers in parentheses indicate 95% confidence interval. BP, Blood pressure; TSH, thyroid-stimulating hormone; NS, not significant. *Only the more relevant differences are shown unless of interest for the study. †Albumin

levels could not be measured in four patients.

Table VII. Endocrine, nutritional, and inflammatory markers in 66 elderly surgical patients with (n = 16) or without (n = 50) established intraabdominal infection at admission Patients with infection TSH (µU/ml) T3 (nmol/L) rT3 (ng/ml) T3/rT3 T4 (nmol/L) Free T4 (nmol/L) Norepinephrine (pg/ml) Epinephrine (pg/ml) Cortisol (nmol/L) IL-6 (pg/ml) CRP (mg/dl) Grip strength (kg) Serum albumin (gm/L) Prealbumin (mg/dl) Retinol BP (mg/dl) APACHE II

Patients without infection

1.48 (0.7-2.2) 0.85 (0.6-1) 0.60 (0.44-0.76) 2.2 (1.4-3.7) 94.2 (83-105) 15.1 (13-17) 297 (198-397) 49.7 (31.7-67.6) 1126 (885-1367) 583 (88-1079) 7.58 (5.1-10) 9.8 (6.1-13.4) 35 (31.8-38.2) 14.1 (11-17) 3.1 (2.4-3.8) 11.5 (9.4-13.7)

1.22 (0.9-1.5) 1.25 (1.1-1.4) 0.35 (0.3-0.4) 4.4 (3.7-5) 98.6 (90-107) 14.7 (13.2-16.1) 308 (253-363) 65.4 (49.6-81.2) 747 (658-844) 117 (98-137) 1.5 (0.8-2.2) 10.7 (9-12.5) 38 (37-40) 18.6 (16.9-20.2) 3.9 (3.5-4.3) 9.3 (8.5-10.1)

p Value NS 0.002 0.0004 0.004 NS NS NS NS 0.0007 0.0008 0.0001 NS 0.03 0.008 NS (0.06) 0.01

Numbers in parentheses indicate 95% confidence interval. See Table IV for abbreviations.

lapping of metabolic derangements between patients with ESS and those with hypoalbuminemia, although the latter constituted a smaller group. With one exception, all the patients with

hypoalbuminemia had ESS. Extensive metabolic derangements were found in patients with hypoalbuminemia, including higher norepinephrine and IL-6 plasma concentrations. In addition, patients

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with low albumin concentrations had a lower grip strength, a finding that has been associated with increased impaired postoperative recovery.18,22 Thus beyond its controversial value as a nutritional parameter,23 hypoalbuminemia at admission appears to be a specific marker of ESS and prolonged hospital stay and should be used as guide for a more appropriate management of the elderly with acute surgical disease. We thank Dr. R. Jardí and Mrs. Núria Prim at the Hospitals de la Vall d’Hebró for their efficiency and help in carrying out the blood analysis. REFERENCES 1. Greenburg AG, Saik RP, Coyle JJ, Peskin GW. Mortality and gastrointestinal surgery in aged. Arch Surg 1981;116:788-92. 2. Rorbaek-Madsen M, Dupont G, Kristensen K, Holm T, Sorensen J, Dahger H. General surgery in patients aged 80 years and older. Br J Surg 1992;79:1216-8. 3. Mansell PI, Rawlings J, Allison SP, Bendall MJ, Pearson M, Bassey EJ, et al. Low anthropometric indices in elderly females with fractured neck of femur. Clin Nutr 1990;9:190-4. 4. Mowé M, Bohmer T, Kindt E. Reduced nutritional status in an elderly population (>70 yr) is probable before disease and possibly contributes to the development of disease. Am J Clin Nutr 1994;59:317-24. 5. Simons RJ, Simon JM, Demers LM, Santen RJ. Thyroid dysfunction in elderly hospitalized patients: effect of age and severity of illness. Arch Intern Med 1990;150:1249-53. 6. Nogués R, Sitges-Serra A, Sancho JJ, Sanz F, Monne J, Girvent M, et al. Influence of nutrition, thyroid hormones and rectal temperature on in-hospital mortality of elderly patients with acute illness. Am J Clin Nutr 1995;61:597-602. 7. De Groot LJ, Larsen PR, Henneman G. Effects of drugs, disease, and other agents on thyroid function: the nonthyroidal illness syndrome. In: The thyroid and its diseases. New York: Churchill Livingstone; 1996. p 137-87. 8. Boelen A, Platvoetter-Schiphorst MC, Wiersinga WM. Association between serum interleukin-6 and serum 3,5,3´-triiodo-thyronine in nonthyroidal illness. J Clin Endocrinol Metab 1993;77:1695-9. 9. Bartalena L, Brogioni S, Grasso L, Velluzzi F, Martino E. Relationship of the increased serum interleukin-6 concentra-

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