Pre-existing cardiac disease, troponin I elevation and mortality in patients with severe sepsis and septic shock.

A prospective, observational study was undertaken to determine the frequency of troponin I elevation and the incidence of pre-existing cardiac disease in patients with severe sepsis and septic shock, and to determine their relationship to mortality. The setting was the surgical intensive care unit of a tertiary care medical centre. Sixty-six consecutive patients admitted with severe sepsis or septic shock requiring pulmonary artery catheterisation for haemodynamic monitoring were studied. Measurement of troponin I was done at the time of pulmonary artery catheterisation and every six to eight hours if there was ongoing tachycardia, hypotension or arrhythmias requiring treatment. Preexisting cardiac disease was determined from the patient and/or family members as well as from the medical record. Significant cardiac history was defined as prior myocardial infarction; abnormal treadmill report, nuclear medicine study or coronary angiogram; history of congestive heart failure or arrhythmia requiring treatment. Forty-two patients (64%) had elevated troponin I at study entrance and 23 patients (35%) had pre-existing cardiac disease. History of cardiac disease was associated with reduced cardiac index and oxygen delivery, and a nearly three-fold increase in mortality (44% vs. 16%, P = 0.03), irrespective of elevated troponin I levels. Troponin I elevation alone was not associated with increased mortality. We conclude that pre-existing cardiac disease and elevated troponin I are commonly found in surgical patients with severe sepsis and septic shock. In our study, pre-existing cardiac disease, and not troponin I elevation, was associated with increased mortality.

Relationship of mortality to increasing oxygen delivery in patients > or = 50 years of age: a prospective, randomized trial.

OBJECTIVE: To investigate the relationship of mortality to early resuscitation using two levels of oxygen delivery (DO2) in critically ill surgical patients > or =50 yrs of age who were stratified into groups: age < or =75 yrs (age 50 to 75 yrs group); and age >75 yrs (age >75 yrs group). DESIGN: A prospective, randomized trial, continued from a previous project. SETTING: Surgical intensive care unit, university affiliated. PATIENTS: Consecutive patients, >50 yrs of age, unable to generate a DO2 of > or =600 mL/min/m2 with fluid resuscitation alone, with a diagnosis of systemic inflammatory response syndrome, sepsis, severe sepsis, septic shock, and/or acute respiratory distress syndrome. INTERVENTIONS: During the first 24 hrs of resuscitation, patients were randomized to receive fluids, blood transfusions, and vasoactive agents in order to achieve DO2 treatment goals of > or =600 mL/ min/m2 in the protocol group and 450 to 550 mL/min/m2 in the control group. MEASUREMENTS AND MAIN RESULTS: One hundred five patients completed the study. In patients aged 50 to 75 yrs, the mortality rate was 21% (9/43) in the protocol group and 52% (12/23) in the control group (p=.01, 95% confidence interval of -58% to -4%). In patients >75 yrs of age, the mortality rate was 57% (12/21) in the protocol group and 61% (11/18) in the control group. Oxygen extraction ratios (O2ER) and oxygen consumption values were significantly (p=.02) lower in the age >75 yrs group compared with the age 50 to 75 yrs group. CONCLUSIONS: Patients 50 to 75 yrs of age receiving a DO2 of > or =600 mL/min/m2 demonstrated a statistically significant (p=.01) improved survival rate over patients in the control group. Patients >75 yrs of age demonstrated no benefit from attempts to increase DO2 to >600 mL/min/m2, and they may have been overtreated as reflected by the lower O2ER values in this age group. Treating to an O2ER that reflects a balance between oxygen consumption and DO2 may be an alternative goal that allows individual titration.

High-volume vs standard fluid therapy in a septic pig model. Impact on pulmonary function.

OBJECTIVE: To compare pulmonary function and peripheral organ blood flow in septic pigs receiving high-volume fluid resuscitation or standard-volume fluid resuscitation with similar goals in oxygen delivery. DESIGN: A prospective study comparing 2 groups of septic pigs. SETTING: A university animal research laboratory. SUBJECTS: Eleven septic pigs. INTERVENTIONS: Basal oxygen delivery was increased from 450 to 550 mL/min to at least 600 mL/min by the sixth hour and maintained for 24 hours. From a baseline pulmonary artery occlusion pressure (PAOP) measurement of approximately 6 mm Hg, the high-volume group (n = 5) was treated until a PAOP measurement of 12 mm Hg was reached and the standard-volume group (n = 6) was treated until a PAOP measurement of 8 mm Hg was reached. Blood transfusions and inotropic agents were added as necessary to reach the oxygen delivery goal. RESULTS: The high-volume group had a significantly greater positive fluid balance, greater weight gain, and a higher PAOP but similar intrapulmonary shunt and extravascular lung water as compared with the standard-volume group. CONCLUSION: Resuscitation with large volumes of fluid in early sepsis with a physiological goal of a higher PAOP to augment oxygen delivery did not cause increased pulmonary edema and oxygenation deficit compared with maintenance of lower cardiac filling pressures.

Ploidy as a prognostic feature in colonic adenocarcinoma.

OBJECTIVE: To determine whether DNA content and cell-cycle kinetic characteristics in Dukes stage B colonic adenocarcinomas provide additional prognostic information in the context of clinicopathologic variables of known significance. DESIGN: Archival, paraffin-embedded tissue blocks from 210 Dukes B colonic adenocarcinomas were retrieved. After confirming stage, tumor cell nuclei were extracted, suspended, and stained. Cell nuclei from adjacent normal colon mucosa were used as controls. SETTING: University-based, tertiary cancer referral center. INTERVENTIONS: Samples obtained from tumors resected at our institution between 1965 and 1984 were analyzed by flow cytometry for DNA index (DI) and percentages of cells in synthesis (S) phase (%S) and in G2 and mitosis (M) phases (%G2M). The data were correlated with 5-year survival. Follow-up was complete in all patients to at least 5 years. RESULTS: Univariate analysis showed that the highest survival rates were associated with DI values near 1 and 2 (diploid and tetraploid tumors, P = .02) and the lowest %G2M values (tumors with fewer mitoses; P = .01). Five-year survival rates also differed significantly between patients with diploid (DI < 1.1) and those with aneuploid (1.1 < DI < 2) tumors (80% vs 64%, respectively; P = .02). Multivariate analysis revealed that race (P < .01), lymphatic or capillary microinvasion (P < .03), and ploidy (P < .05) were significantly associated with outcome. The influence of ploidy, race, and microinvasion on 5-year survival was estimated with logistic regression, and 8 subgroups of patients emerged with 5-year survival probabilities ranging from 39% for black patients with aneuploid tumors and microinvasion to 88% for white patients with diploid tumors and no microinvasion. CONCLUSIONS: Tumor DNA content provides additional independent information that allows further refinement of our prognostic ability in patients with Dukes B colonic adenocarcinoma. This may aid in the identification of a cohort of patients who may potentially benefit from aggressive adjuvant therapy.

Chromosome 17p allelic loss in colorectal carcinoma. Clinical significance.

OBJECTIVE: To correlate allelic losses on chromosomes 5q, 8p, 17p, and 18q in colorectal adenocarcinomas with histopathologic features of known prognostic significance. DESIGN: DNA was extracted from paired samples of 56 fresh-frozen colorectal adenocarcinomas (one classified as Dukes' stage A, 22 as Dukes' stage B, 27 as Dukes' stage C, and six as Dukes'stage D) and adjacent normal mucosa. SETTING: Specimens were resected at the University of Chicago (Ill) and the University of Padova (Italy) in 1991. PATIENTS: Samples were obtained from consecutive patients. INTERVENTIONS: Chromosomes 5q, 8p, 17p, and 18q were studied for loss of heterozygosity by means of Southern hybridization blot analysis of restriction fragment length polymorphisms, and the results were correlated with pathologic tumor stage, degree of differentiation, and lymphatic and/or vascular microinvasion. RESULTS: Chromosomes 17p and 18q exhibited the highest frequency of loss of heterozygosity (40.6% and 48.8%, respectively). Most of the allelic losses were found in advanced tumors (60% in Dukes' stages C and D combined). A statistically significant correlation was found between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion (P < .01, Fisher's Exact Test). CONCLUSIONS: There was a significant correlation between loss of heterozygosity on chromosome 17p and the presence of lymphatic and/or vascular microinvasion in colorectal adenocarcinoma, a known stage-independent negative prognostic risk factor. Detection of loss of heterozygosity on chromosome 17p may identify a group of patients who may benefit from more aggressive surgical and/or early adjuvant therapy.

Analysis of clinicopathologic prognostic features in patients with gastric adenocarcinoma.

BACKGROUND: We evaluated the influence of several clinicopathologic variables on 5-year actuarial survival rate after curative resection of gastric adenocarcinoma. METHODS: Clinical characteristics were retrieved from the records of all patients who underwent gastric resection for curative intent between 1965 and 1986 at The University of Chicago Medical Center, and follow-up was obtained from our tumor registry. Pathologic characteristics were determined from a detailed review of all available histopathologic slides. RESULTS: One hundred seventy-eight patients underwent a curative resection during the study period at our institution. Overall 5-year actuarial survival rate was 29%. The relationship between clinicopathologic variables and 5-year survival rate was evaluated by Kaplan-Meier survival curve construction and chi-squared analysis. Lymphatic and/or capillary microinvasion (absent vs present, p < 0.001), tumor location (antrum and body vs gastroesophageal junction, p = 0.05), local extent of disease (limited to the gastric wall versus involving adjacent organs, p = 0.003), stage (absence versus presence of lymph node metastases, p < 0.001), Lauren type (intestinal versus diffuse, p < 0.01), and Ming type (expanding versus infiltrative, p < 0.02) significantly influenced survival. When a multivariate analysis with logistic regression of 5-year survival was performed, lymphatic and/or capillary microinvasion emerged as the only statistically significant, independent prognostic factor associated with long-term survival (p = 0.039). If microinvasion was omitted from the analysis, lymph node metastases (p < 0.05) and the extension to adjacent organs (p < 0.04) became the only statistically significant variables. Multiple correlation analyses suggested that microinvasion is an early histopathologic finding that correlates with a more aggressive natural history. CONCLUSIONS: Lymphatic and/or capillary microinvasion is a more powerful predictor of 5-year survival than lymph node metastases or tumor extension to adjacent organs. Correlation among clinicopathologic variables suggests that microinvasion may represent an early finding, serving as a potential marker for a biologically more aggressive tumor.