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.

Eosinophilia as a marker of adrenal insufficiency in the surgical intensive care unit.

BACKGROUND: Because hemodynamic instability may have several causes in critically ill patients, adrenal insufficiency may not be readily diagnosed. Eosinophilia has been described in patients with chronic adrenal insufficiency but not in critically ill patients. The goal of this study was to determine whether eosinophilia could serve as a marker of adrenal insufficiency in critically ill patients. STUDY DESIGN: During a 1-year period, all surgical patients admitted to the surgical intensive care unit with an eosinophil count greater than 3 percent were prospectively studied. To diagnose adrenal insufficiency, the synthetic corticotropin (cosyntropin) stimulation test was used. RESULTS: Eosinophilia was diagnosed in 31 patients, 7 (23 percent) of whom had adrenal insufficiency. The mean time interval to diagnosis was 13.7 days (range, 4 to 39 days). In 82 percent of the patients treated with hydrocortisone, a response was evidenced within 24 hours of treatment by a decrease in the required inotropic support by more than 50 percent, an increase in the mean arterial blood pressure of more than 25 percent, or both. CONCLUSIONS: New-onset eosinophilia may be a useful marker for adrenal insufficiency. Prompt testing and diagnosis may avoid the occurrence of a treatable, life-threatening condition.

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.

Frequency of mortality and myocardial infarction during maximizing oxygen delivery: a prospective, randomized trial.

OBJECTIVES: To determine the frequency of myocardial infarction and mortality during treatment that increased oxygen delivery (DO2) to > or = 600 mL/min/m2. To define the characteristics of patients achieving a high DO2 without inotropes in order to guide future studies. DESIGN: A prospective, randomized, controlled trial. SETTING: Two surgical intensive care units at The Queen's Medical Center in the University of Hawaii Surgical Residency Program. PATIENTS: Eighty-nine surgical patients (> or = 18 yrs of age), who were admitted to a surgical intensive care unit and who required pulmonary artery catheter monitoring, were selected for the study. Diagnoses included sepsis, septic shock, adult respiratory distress syndrome, or hypovolemic shock. Patients facing imminent death were excluded from the study. INTERVENTIONS: The treatment group received fluid boluses, blood products, and inotropes, as needed, to achieve a DO2 of > or = 600 mL/min/m2 in the first 24 hrs. Using the same interventions, we treated the control group to reach a DO2 of 450 to 550 mL/min/m2. MEASUREMENTS AND MAIN RESULTS: Hemodynamic measurements were obtained every 4 hrs until the pulmonary artery catheter was removed. DO2 and oxygen consumption were calculated by standard formulas. Serial creatine kinase myocardial fraction and electrocardiograms were documented for the first 48 hrs after study entry and for any new onset of arrhythmia or increasing hemodynamic instability. The patients who generated a high DO2 (> or = 600 mL/min/m2) with only preload treatment were reflective of patients with better cardiac reserve and low mortality rates. These patients, from both treatment and control groups, were excluded in the final analysis. The treatment group who received inotropes to achieve the high DO2 had a 14% mortality rate. Those patients who failed to achieve the high DO2 had a 67% mortality rate, and the control group who achieved a normal DO2 had a 62% mortality rate (p = .005). The frequency of myocardial infarction after study entry was 5.6% (five of 89 patients). This rate was not higher among the groups who received inotropes. Logistic regression analysis showed that age of > or = 50 yrs could be used to classify patients as not self-generating, with an 83% chance of being correct. CONCLUSIONS: The group that required catecholamines to achieve a DO2 of > or = 600 mL/min/m2 had a lower mortality rate, with no increase in the frequency of myocardial infarction. Future prospective, controlled trials examining select groups of patients (age > or = 50 yrs) may demonstrate a difference between control and treatment groups by eliminating the majority of patients who generate the high DO2 with only preload augmentation.

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.

Evaluation of the clinical usefulness of thermodilution volumetric catheters.

OBJECTIVE: To determine if treatment modalities (fluid, inotropes, and blood) would be altered based on preload measurements of right ventricular end-diastolic volume index measured by fast response thermodilution catheter, as compared with pulmonary artery occlusion pressure (PAOP). DESIGN: A prospective clinical trial. SETTING: An 11-bed surgical intensive care unit (ICU) at The Queen's Medical Center, an affiliate of the University of Hawaii Surgical Residency program. PATIENTS: Surgical ICU patients who required pulmonary artery catheters, except those patients with arrhythmias or history of tricuspid valve disease. INTERVENTIONS: During the first 48 hrs after catheter insertion, hemodynamic data were obtained at least every 4 hrs. Treatment of low preload was initiated only if clinical indications were present. These indications included a mean arterial pressure of < 70 mm Hg, heart rate of > 120 beats/min, urine output of < 40 mL/hr, stroke volume of < 40 mL/m2 with oxygen delivery of < 450 mL/min/m2, and lactic acidosis. Volume infusion was considered if PAOP was < 18 mm Hg and right ventricular end-diastolic volume index was < 140 mL/m2. Treatment was given tohigh preload, defined as a PAOP of > 18 mm Hg to prevent pulmonary edema. When PAOP and right ventricular end-diastolic volume index gave conflicting information, other clinical parameters were assessed to determine treatment. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients requiring 70 catheters were evaluated for the study. Thirteen patients with 46 pairs of data points completed the study. Fourteen patients were excluded from analysis due to irregular heart rate, poor quality of cardiac output at the time of volume infusion, or lack of major volume manipulation. PAOP and right ventricular end-diastolic volume index measurements agreed in 42 of 46 instances (PAOP of < 18 mm Hg, right ventricular end-diastolic volume index of < 140 mL/m2), leading to fluid treatment. In one instance, PAOP was > 18 mm Hg, right ventricular end-diastolic volume index was < 140 mL/m2, and the patient had normal blood pressure and good urine output. PAOP was used in this instance as a guide to diurese the patient, which led to improvement of heart rate and stroke volume index. Three measurements in two patients with high intra-abdominal pressure indicated a PAOP of > 18 mm Hg with right ventricular end-diastolic volume index of < 140 mL/m2. A rigid abdomen accompanied hypotension, tachycardia and low urine output. Thus, a fluid bolus was administered, resulting in improved blood pressure, stroke volume, and heart rate. PAOP were obtained at end-expiration. Positive end-expiratory pressure (PEEP) was removed for < 1 sec, if patients were on PEEP > or = 10 cm H2O, to avoid the effects of high intrapleural pressure on PAOP readings. Cardiac output was measured at end-expiration, and stroke volume index and right ventricular end diastolic volume index were derived. CONCLUSIONS: In this small sample of surgical patients with sepsis, adult respiratory distress syndrome, and hemorrhagic shock (n = 13), the additional information derived from right ventricular end-diastolic volume index did not change treatment in 43 of 46 instances. However, patients with increased intra-abdominal pressures may show misleadingly high PAOP despite low preload. These patients clearly benefitted from the additional information derived from ventricular volume measurements. Additionally, clinicians who are reluctant to take off-PEEP PAOP may also find this catheter useful.

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.