Effects of metformin hydrochloride on blood glucose and insulin responses to oral dextrose in horses.

REASONS FOR PERFORMING STUDY: Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. OBJECTIVES: To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. STUDY DESIGN: Therapeutic cross-over study. METHODS: Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and without metformin, before and after induction of IR with dexamethasone. Metformin was administered by nasogastric tube at 30 mg/kg bwt 1 h before administration of dextrose. Glucose and insulin concentrations in plasma/serum were measured at regular intervals during each test. Linear mixed models were specified for each predetermined outcome variable, and for each model the 'treatment' was included as a fixed effect with 4 categorical levels (none, metformin, dexamethasone and dexamethasone with metformin) and horse accounted for as a random effect. RESULTS: In healthy horses, the administration of metformin resulted in a statistically significant reduction in peak glucose concentration (P = 0.002), area under the glucose curve (P<0.001) and insulin concentration 120 min after dextrose administration (P = 0.011). Following the induction of IR, administration of metformin was associated with significant differences in peak glucose concentration (P<0.001), the percentage increase in glucose concentration (P = 0.010), the area under the glucose curve (P<0.001) and insulin concentration at 120 min (P = 0.034) and 150 min after dextrose administration (P = 0.014). CONCLUSIONS: Metformin resulted in reduced glycaemic and insulinaemic responses both in healthy horses and in horses with experimentally induced IR. POTENTIAL RELEVANCE: Metformin may benefit horses with naturally acquired IR by reducing glycaemic and insulinaemic responses to dietary nonstructural carbohydrates. Further investigations into the mechanisms of action of metformin in horses and controlled clinical trials are warranted.

Pressure ulcer prevention: a randomized controlled trial of 2 risk-directed strategies for patient surface assignment.

OBJECTIVE: To compare the clinical utility, in terms of incidence of pressure ulcer (PU) development, and economic impact of 2 programs of patient surface assignment for PU prevention. DESIGN: Randomized controlled clinical trial with economic evaluation. SETTING: 30-bed multidisciplinary intensive care unit (ICU), serving as the regional trauma center. PATIENTS: 144 consecutive eligible patients at risk for the development of PUs. INTERVENTION: PU risk was assessed on admission using the Skin Ulcer Risk Evaluation (SURE) Score, and patients were randomized to either the experimental (purchase) or control group (purchase/rent). Based on their SURE Score, patients were assigned a specialty surface if needed. Patients received head-to-toe skin assessments twice weekly, new PUs were documented, a new SURE Score was calculated, and specialty surfaces were upgraded or downgraded as necessary. OUTCOMES: The incidence of PUs by site and severity, and cost. ANALYSES: Multivariate logistic regression and decision modeling. RESULTS: No significant differences were detected between groups with respect to baseline population characteristics, nor in the development of PUs. Predictors of PU development were ICU length of stay and SURE Score. The experimental (purchase) group was the less costly strategy. Under baseline assumptions, surface costs per at-risk patient were $76 CDN and $171 CDN in the experimental and control groups, respectively. The savings of $95 CDN per at-risk patient translates into conservative annual savings of $47,500 CDN. CONCLUSIONS: Using an objective, risk-based method of patient surface assignment, the authors compared the clinical and economic outcomes of 2 programs of PU prevention. In a direct comparison of alternatives, the strategy that emphasized purchased rather than rented products proved to be the more economical. Finally, this approach illustrates how by prospectively capturing data on both the costs and consequences of competing alternatives, a more objective and informed decision-making process can result.

A comparison of sucralfate and ranitidine for the prevention of upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group.

BACKGROUND: Critically ill patients who require mechanical ventilation are at increased risk for gastrointestinal bleeding from stress ulcers. There are conflicting data on the effect of histamine H2-receptor antagonists and the cytoprotective agent sucralfate on rates of gastrointestinal bleeding, ventilator-associated pneumonia, and mortality. METHODS: In a multicenter, randomized, blinded, placebo-controlled trial, we compared sucralfate with the H2-receptor antagonist ranitidine for the prevention of upper gastrointestinal bleeding in 1200 patients who required mechanical ventilation. Patients received either nasogastric sucralfate suspension (1 g every six hours) and an intravenous placebo or intravenous ranitidine (50 mg every eight hours) and a nasogastric placebo. RESULTS: The patients in the two groups had similar base-line characteristics. Clinically important gastrointestinal bleeding developed in 10 of 596 (1.7 percent) of the patients receiving ranitidine, as compared with 23 of 604 (3.8 percent) of those receiving sucralfate (relative risk, 0.44; 95 percent confidence interval, 0.21 to 0.92; P=0.02). In the ranitidine group, 114 of 596 patients (19.1 percent) had ventilator-associated pneumonia, as compared with 98 of 604 (16.2 percent) in the sucralfate group (relative risk, 1.18; 95 percent confidence interval, 0.92 to 1.51; P=0.19). There was no significant difference between the groups in mortality in the intensive care unit (ICU) (23.5 percent in the ranitidine group and 22.9 percent in the sucralfate group) or the duration of the stay in the ICU (median, nine days in both groups). CONCLUSIONS: Among critically ill patients requiring mechanical ventilation, those receiving ranitidine had a significantly lower rate of clinically important gastrointestinal bleeding than those treated with sucralfate. There were no significant differences in the rates of ventilator-associated pneumonia, the duration of the stay in the ICU, or mortality.

How to use an article on therapy or prevention: pneumonia prevention using subglottic secretion drainage.

Evidence based critical care medicine involves integrating clinical experience, expertise, and patient preferences with explicit, systematic, and judicious use of current best evidence in making medical decisions. Published evidence has many sources: research from the basic sciences of medicine, and from patient-centered clinical research on the accuracy of diagnostic tests, the power of prognostic markers, and the effectiveness and safety of preventive, therapeutic, rehabilitative, and palliative interventions. When critically appraising a clinical article for potential use in intensive care unit (ICU) practice, the first question we ask ourselves is: Is this study valid? If examination of the study methods reveals that the design is rigorous, we can turn to the two other key questions: What are the results? and, Will the results help me care for my patients? This approach may aid in the interpretation of an article on therapy or prevention; in it we discuss a strategy designed to prevent ventilator associated pneumonia in critically ill patients.

Polymerase chain reaction-and RNA hybridization-based method for the investigation of deep-seated candidiasis.

OBJECTIVE: To determine the usefulness of a polymerase chain reaction (PCR) and RNA hybridization method for the diagnosis of invasive candidiasis and to compare its sensitivity with blood cultures. DESIGN: Blood cultures and a blood sample for PCR were taken from patients with suspected invasive candidiasis. A 105 base pair conserved segment within the rDNA of Candida species was amplified. The amplicon was detected by hybridization and gel electrophoresis. SETTING: Intensive care units of two tertiary care hospitals. PATIENTS: One hundred and eighteen patients 16 years of age or older with four more risk factors for invasive candidiasis were enrolled. Present or recent past treatment with broad spectrum antibiotics, cancer chemotherapy, immunosuppressive drugs, granulocytopenia or granulocytosis, intravascular catheterization, tracheal intubation, recent abdominal surgery and parenteral nutrition were considered risk factors. RESULTS: Forty-three patients had invasive candidiasis. PCR detected infections in 28 and 26 patients (sensitivity 65.1% and 60.4%) by hybridization and gel electrophoresis, respectively. The sensitivity of blood cultures was 58.1%. Of 25 patients with positive blood cultures, 17 were positive by PCR with the hybridization method. Eleven patients with invasive candidiasis had negative blood cultures but were positive by PCR. CONCLUSION: PCR, especially with a hybridization detection method, is more sensitive than blood culture for invasive candidiasis and may facilitate the diagnosis of nonfungemic disease.

Circulatory sequelae of administering CPAP in hyperdynamic sepsis are time dependent.

Evidence questions the circulation's ability to acutely compensate for abrupt changes in O2 delivery (Qo2). Because both sepsis and continuous positive airway pressure (CPAP) may alter the metabolic regulation of tissue oxygenation, we designed an experiment to determine the interaction, if any, between sepsis and time on circulatory homeostasis after the application of CPAP. Twenty-four sheep were randomized to cecal ligation and perforation (CLP) or sham procedure (Sham) and then rerandomized to receive either CPAP (10 mmHg) or no CPAP (No CPAP; CLP/CPAP, n = 8; CLP/No CPAP, n = 8; Sham/CPAP, n = 4; Sham/No CPAP, n = 4). Forty-eight hours later, CLP animals demonstrated an elevated cardiac index (+63%), systemic Qo2 (+49%), and systemic O2 uptake (+28%). Organ blood flow, measured with radiolabeled microspheres, was augmented to the heart and depressed in organs comprising the splanchnic circulation. Compared with the CLP/No CPAP group and both Sham groups, myocardial Qo2 in the CLP/ CPAP group was significantly elevated when measured both 2 and 8 h after CPAP. These changes were unrelated to differences in mean heart work between the study groups. Simultaneously, QO2 to all of the small gut, large gut, pancreas, and kidney in the CLP/CPAP group was elevated during the 2-h study yet reverted to levels not different from baseline by the 8-h study. These data demonstrate 1) a unique sepsis x time interaction with the use of 10 mmHg of CPAP, particularly in the "nonvital" circulations, and 2) CPAP effects on the septic coronary circulation, which were unexplained by changes in external determinants of myocardial O2 need.

Neuromuscular disorders associated with failure to wean from the ventilator.

OBJECTIVE: To determine, by retrospective chart analysis, the frequency, type and significance of neuromuscular disorders in patients whose clinical features suggested a neuromuscular cause of failure to wean. BACKGROUND: Failure to wean is a common and difficult problem in critical care units. While a neuromuscular cause may be suspected in some patients, the frequency and type has not been determined utilizing comprehensive electrophysiological studies of limbs and the respiratory system. Such knowledge may aid in patient management and prognosis. METHODS: The clinical setting was a critical care/trauma centre that admits 1500 patients per year, approximately 500 being on ventilators for longer than five days. We analyzed the hospital charts of 40 patients admitted to the unit during three years, whose respiratory assessment suggested a neuromuscular cause for failure to wean from the ventilator. To investigate this possibility, we performed electrophysiological studies of the limbs and also of the respiratory system by phrenic nerve conduction and needle electromyography of the chest wall and diaphragm. The results were compared to 25 healthy controls. RESULTS: 38 of 40 patients (95%) had a neuromuscular disorder: 25--critical illness polyneuropathy, 2--Guillain-Barré syndrome, 4--diabetic and critical illness polyneuropathy, 2--uremic and critical illness polyneuropathy, 10--an abnormality of central drive, 5--unilateral phrenic nerve palsy, 3--a neuromuscular transmission defect, and 5--a primary myopathy. Fifteen (38%) had a combination of disorders. Patients with more severe polyneuropathy took longer to wean, a mean of 136 versus 52 days (p = 0.007). The severity of the polyneuropathy had no effect on mortality. CONCLUSIONS: Electrophysiological studies of limbs and the respiratory system are together valuable in confirming the presence, and identifying the specific type of neuromuscular cause for difficulty in weaning from the ventilator. This information is important in patient management and prognosis.

Radical hysterectomy for recurrent carcinoma of the uterine cervix after radiotherapy.

Patients with small recurrent cervical carcinomas following radiation therapy may be salvaged with radical hysterectomy rather than exenteration. Between 1953 and 1993, 50 patients underwent radical hysterectomy for persistent (n = 18) or recurrent (n = 32) cervical cancer after primary radiotherapy. The mean age of the cohort was 44 years (range, 23-70). Histologic types were squamous in 46, adenocarcinoma in 3, and adenosquamous in 1. Of 37 patients with staged disease, 24 had stage IB/IIA, 7 had stage IIB, 2 had stage IIIA, and 2 had stage IIIB. Combination radiotherapy, consisting of 40-45 Gy external-beam radiation plus brachytherapy (mean 6980 mg/hr), was performed in 32 patients (64%). In the 32 patients with recurrent lesions, the median interval from definitive radiotherapy to radical hysterectomy was 16 months (4-301), with 19 of these patients (60%) presenting within the first 24 months. Patients with persistent carcinomas underwent radical hysterectomy after a median observation interval of 2 months (1-4). A class II or III radical hysterectomy was performed in 39 (78%) cases. Pelvic and para-aortic lymph node samplings were performed in 39 patients (78%), including 33 (66%) who underwent complete pelvic lymphadenectomy. Among those sampled, 5 (13%) had metastatic nodal disease. All 5 patients died of disease at a median 13 months after surgery. Severe postoperative complications occurred in 21 patients (42%). The most common site of injury was the urinary tract, with 14 patients (28%) developing vesicovaginal or rectovaginal fistulae, 11 (22%) developing ureteral injuries, and 10 (20%) developing severe long-term bladder dysfunction. There was one postoperative death from sepsis among the entire population. Patients with abnormal preoperative intravenous pyelograms (P < 0.05), patients with recurrent presurgical lesions (P < 0.05), and patients with postoperative pelvic cellulitis (P < 0.01) were more likely to develop fistulae. The 5- and 10-year actuarial survival rates for all cases was 72 and 60%, respectively. Tumor size at radical hysterectomy was significantly associated with survival. Five-year actuarial survival in 12 of 44 patients (27%) with identifiable lesion diameters less than 2 cm was 90% compared with 64% in patients with larger lesions (P < 0.01). Prolonged disease-free survival occurred in 26 of 50 patients (52%) who had known disease status at follow-up, whereas recurrence after radical hysterectomy was seen in 24 patients (48%).(ABSTRACT TRUNCATED AT 400 WORDS)

Hematocrit modifies the circulatory control of systemic and myocardial oxygen utilization in septic sheep.

OBJECTIVE: To describe the relationship between hematocrit and oxygen utilization before and after the onset of a hyperdynamic septic state. DESIGN: Prospective, observational study. SETTING: Laboratory of a large university-affiliated medical school. SUBJECTS: Thirty mature sheep, each weighing 30 to 40 kg (0.9 to 1.1 m2 body surface area). INTERVENTIONS: After baseline measurements, cecal ligation and perforation were used to establish an intra-abdominal source of infection. The abdominal wound was closed and animals were studied on the second postoperative day. An increase in cardiac output of > or = 30% was used to arbitrarily define the onset of sepsis. Repeat measurements were performed and the animal was killed. RESULTS: The circulatory response to this septic insult included an increase in both cardiac index (change, baseline to sepsis, delta +2.24 +/- 0.75 L/min/m2; p < .01) and myocardial blood flows (delta +76.4 +/- 56 mL/100 g/min; p < .01). We found a negative correlation between the hematocrit and cardiac index (r2 = .21; p < .01) during the septic study, and noted that the amount (p < .01) of this correlation was significantly greater in the septic than the nonseptic study. Concurrently, the negative correlation observed between hematocrit and whole-body oxygen extraction (r2 = .21; p < .01) was significantly lower (p < .01) across the range of hematocrit values examined during the septic study vs. the similar relationship in the nonseptic study (r2 = .27; p < .01). The increase in myocardial oxygen consumption paralleled the relationship between cardiac work and hematocrit in the septic study, and was accompanied by increases in both myocardial blood flows (r2 = .25; p < .01) and myocardial oxygen extraction (r2 = .35; p < .01). CONCLUSIONS: The normal circulatory compensation to anemia in hyperdynamic sepsis includes increases in cardiac index and whole-body oxygen extraction, although greater reliance is likely placed on the use of systemic flow reserve to maintain tissue oxygen uptake in septic vs. healthy study conditions. Furthermore, increased reliance on myocardial oxygen extraction in sepsis suggests that the normal flow-reserve supporting myocardial oxygen availability may be limited in this syndrome.

Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group.

BACKGROUND: The efficacy of prophylaxis against stress ulcers in preventing gastrointestinal bleeding in critically ill patients has led to its widespread use. The side effects and cost of prophylaxis, however, necessitate targeting preventive therapy to those patients most likely to benefit. METHODS: We conducted a prospective multicenter cohort study in which we evaluated potential risk factors for stress ulceration in patients admitted to intensive care units and documented the occurrence of clinically important gastrointestinal bleeding (defined as overt bleeding in association with hemodynamic compromise or the need for blood transfusion). RESULTS: Of 2252 patients, 33 (1.5 percent; 95 percent confidence interval, 1.0 to 2.1 percent) had clinically important bleeding. Two strong independent risk factors for bleeding were identified: respiratory failure (odds ratio, 15.6) and coagulopathy (odds ratio, 4.3). Of 847 patients who had one or both of these risk factors, 31 (3.7 percent; 95 percent confidence interval, 2.5 to 5.2 percent) had clinically important bleeding. Of 1405 patients without these risk factors, 2 (0.1 percent; 95 percent confidence interval, 0.02 to 0.5 percent) had clinically important bleeding. The mortality rate was 48.5 percent in the group with bleeding and 9.1 percent in the group without bleeding (P < 0.001). CONCLUSIONS: Few critically ill patients have clinically important gastrointestinal bleeding, and therefore prophylaxis against stress ulcers can be safely withheld from critically ill patients unless they have coagulopathy or require mechanical ventilation.

Does implementing pulse oximetry in a critical care unit result in substantial arterial blood gas savings?

OBJECTIVES: To examine the impact of pulse oximetry on the use of arterial blood gas and other laboratory determinations and to examine predictors of the use of arterial blood gas measurements. DESIGN: Before (preoximetry)/after (postoximetry) study. SETTING: Thirty-bed multidisciplinary critical care unit. PATIENTS: Consecutive admissions of 300 patients (150 before and 150 after oximetry). MEASUREMENTS: For each patient examined, the number of arterial blood gas determinations, serum electrolyte levels, complete blood chemistries, arterial lactate levels, and creatinine samples were recorded for the initial 9 days of the stay in the critical care unit. These data were stratified by nursing shift (day vs night) and by the source of the admission (medical vs surgical). Other information collected included demographic variables, the severity of illness, the length of stay in the critical care unit, and various ventilatory parameters. RESULTS: Introducing pulse oximetry was associated with a marginal (10.3 percent; p < 0.025) reduction in the use of arterial blood gas determinations. This decrease was accounted for by changes occurring on the night shift and in the surgical patient. These findings were also observed for serum electrolyte determinations. No significant differences in the use of arterial blood gas measurements were found for medical patients. No significant differences were found in the use of arterial lactate levels, complete blood chemistries, or creatinine determinations. Significant predictors of arterial blood gas determinations included the number of days intubated, the number of ventilator orders, the number of days on an inspired oxygen content (FIO2) greater than 50 percent, and the acute physiology and chronic health evaluation II (APACHE II) score. CONCLUSIONS: The implementation of pulse oximetry in this manner gives an idea how effective the technology will be in reducing the use of arterial blood gas determinations without guidelines for the use of pulse oximetry. As only a marginal decrease was observed in the total population of medical and surgical patients, and only on the night shift, formal and standardized guidelines for the most efficient use of pulse oximetry should be considered. If these were considered, pulse oximetry may indeed make a significant contribution to improving the efficiency of care services.

Aborted exenterative procedures in recurrent cervical cancer.

Preparation for pelvic exenteration is a traumatic experience for every patient, especially so when the procedure has to be aborted because of advanced disease. This occurred in 111 of 394 patients who underwent exploration for possible pelvic exenteration for recurrent cervical cancer at the University of Texas M. D. Anderson Cancer Center between 1970 and 1990. We reviewed these cases to better delineate preoperative factors predictive of unresectability. Distributions of initial stages and pathological diagnoses were similar to those for all cases of primary cervical cancer. The median time from primary therapy to recurrence was 12 months. The reasons for aborting the procedure included the presence of peritoneal disease in 49 patients (44%), for which the only preoperative finding with significant correlation was the presence of a pelvic mass (P = 0.03). Other reasons for aborting the procedure included nodal disease in 45 patients (40%), related to a short interval from primary therapy (P = 0.008) and the notation of fibrosis on preoperative exam (P = 0.01), parametrial fixation in 15 patients (13%), and hepatic lesions or bowel involvement in 5 patients (4.5%). Peritoneal cytology was negative in 61 of 79 patients (77.2%) and was of predictive value only in patients with adenocarcinoma. In conclusion, disseminated disease can seldom be detected during preoperative work-up. Evaluation of nodal status with computed tomography, lymphangiogram and directed fine-needle aspiration, and examination of peritoneal cytology in cases with adenocarcinoma, are the best available means of reducing the number of aborted procedures.

Clinical utility and cost-effectiveness of an air suspension bed in the prevention of pressure ulcers.

OBJECTIVE: To determine, in critically ill patients at risk, both the clinical utility and cost-effectiveness of using an air suspension bed in the prevention of pressure ulcers. DESIGN: Randomized, parallel group, controlled clinical trial with accompanying cost-effectiveness analysis. SETTING: 30-bed multidisciplinary intensive care unit. PATIENTS: 100 consecutive patients at risk for the development of pressure ulcers randomly assigned to receive treatment on either an air suspension bed or a standard intensive care unit bed. Patients considered at risk were those at least 17 years of age with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 15 who had an expected intensive care unit stay of at least 3 days. MAIN OUTCOME MEASURES: The development of pressure ulcers by site and severity and the costs associated with each of the two programs. RESULTS: The air suspension bed was associated with fewer patients developing single, multiple, or severe pressure ulcers. In patients at risk, the use of an air suspension bed in the prevention of pressure ulcers was a cost-effective therapy. CONCLUSIONS: Despite intense nursing care, pressure ulcers are more prevalent in the critically ill patient population than in the general hospital population. Air suspension therapy provides a clinically effective means of preventing pressure ulcers in these patients. In patients at risk, air suspension therapy was a cost-effective means of managing pressure ulcers compared with the standard hospital bed.

Second genital primary squamous neoplasms in vulvar carcinoma: viral and histopathologic correlates.

OBJECTIVE: To determine whether vulvar squamous cell carcinomas associated with certain morphologic features and/or human papillomavirus (HPV) nucleic acids were more likely to be associated with other genital primary squamous neoplasms. METHODS: We surveyed 169 invasive squamous cell carcinomas of the vulva and correlated associated vulvar intraepithelial neoplasia (VIN), invasive growth patterns resembling VIN (intraepithelial-like or basaloid), and the presence of HPV nucleic acids by in situ hybridization with a history of a second primary squamous neoplasm of the genital tract. RESULTS: Twenty-two patients (13%) had a history of a second primary. An intraepithelial growth pattern or an associated VIN correlated significantly with HPV, at P = .0005 and P = .007, respectively, and with a second primary, at P = .077 and P = .009, respectively. When HPV-positive, the same histologic variables correlated with a second primary at P = .099 and P = .25, respectively. Compared with cases lacking both these histologic features and HPV, they correlated with multifocal disease at P = .01 and P = .003. CONCLUSIONS: The findings of HPV nucleic acids, tumor growth patterns, and associated VIN are interrelated and confer risk of other genital primary neoplasms in women with vulvar carcinoma. This supports the concept that subsets of vulvar carcinoma may be distinguished not only by morphology and HPV DNA, but also by a distinctly different risk of a second genital primary neoplasm.

The effect of various sympathomimetics on the regional circulations in hyperdynamic sepsis.

Because sepsis is characterized by a depression in vascular reactivity, we hypothesized that changes in organ blood flows (Q) would differ between the nonseptic and septic state during the infusion of sympathomimetics. Therefore we examined the (sepsis x organ Q) interaction during the infusion of five sympathomimetics in 36 mature, awake sheep before and after cecal ligation and perforation produced hyperdynamic sepsis. A 3-hour infusion of dobutamine, norepinephrine, dopamine, dopexamine, or salbutamol was compared with that of placebo during both nonseptic and septic studies; drug infusion was titrated to an increase in cardiac index of greater than 20%. Increased plateau infusion doses of norepinephrine (+305%), salbutamol (+275%), dopamine (+70%), and dobutamine (+49%) were required to achieve predefined treatment guidelines during the septic versus nonseptic study. Few differences in the regional effects of individual sympathomimetics were found in the nonseptic study, although infusion of sympathomimetics was accompanied by a redistribution of systemic Q toward the heart and away from the brain, kidney, small intestine, liver, and pancreas. In the septic study, however, the sympathomimetic infusions were not accompanied by the redistribution of Q away from small intestine and liver that was demonstrated in the nonseptic study. Therefore (1) the depressed vascular reactivity in hyperdynamic sepsis altered the dose profile of exogenous sympathomimetics required to augment systemic Q, and (2) the (sepsis x sympathomimetic) interaction was characterized by a depression in the anticipated redistribution of organ Q from "nonvital" to "vital" circulations.

Pelvic exenteration in the elderly patient.

Advanced age is frequently considered a contraindication to radical exenterative surgery. We reviewed the outcomes of 63 patients age 65 years or older who underwent pelvic exenteration between 1960-1991 at The University of Texas M. D. Anderson Cancer Center. Sixty-three percent had preexisting medical illnesses. Major or potentially life-threatening complications were noted in 38% of the patients. An additional 38% experienced minor complications. Sixty percent experienced one or more infectious complications, including pyelonephritis, wound infection, sepsis, and flap necrosis. When both major and minor complications were considered, infectious morbidity was the single largest category. Although they are not life-threatening, nonspecific infectious morbidity and transient confusion were the most frequent individual complications, occurring in 26 and 24% of patients, respectively. Twenty-four percent of the patients experienced no complications. Thirty-four percent of the postoperative survivors suffered late major morbidity. Operative mortality was 11%; multisystem failure was the most frequent cause of death. After a mean follow-up of 4 years, 22 patients were alive with no clinical evidence of disease. Twenty-one patients died of recurrent disease, with a median time to recurrence of 9.6 months. The 5-year survival rate for the group was 46%. In comparison, 363 patients younger than age 65 who underwent exenteration during the same period experienced an operative mortality rate of 8.5% and a 5-year survival rate of 45%, neither of which were significantly different from the rates found for the older group (P = .51 and .52, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of sepsis and sepsis plus sympathomimetics on myocardial oxygen availability.

The ability to regulate myocardial blood flows (Q) in accord with changing myocardial O2 needs may be depressed in sepsis. This could be an important concern when sympathomimetics are used to augment systemic oxygen delivery (QO2) in this syndrome as increased myocardial O2 needs may accompany an infusion of this class of drugs. Therefore after measuring the effect of sepsis on myocardial O2 metabolism, we then infused various sympathomimetics to evaluate the sepsis+sympathomimetic interaction on myocardial QO2. We measured Q to the left (LV) and right (RV) ventricles by the radioactive microsphere technique in 36 unanesthetized mature sheep, before and during the infusion of dopamine, dobutamine, dopexamine, norepinephrine, salbutamol, or placebo. Randomly selected for infusion, these drugs were titrated to augment the thermodilution-derived cardiac index (CI) by greater than 20%. This study was repeated 24-48 h after cecal ligation and perforation had resulted in a hyperdynamic septic state [change (delta) in CI = sepsis - baseline = +54%; P less than 0.01]. During the septic study, both Q-LV (delta = +80%; P less than 0.01) and Q-RV (delta = +84%; P less than 0.01) were increased above baseline values; the augmented Q to both LV and RV was directly correlated with the arterial perfusion pressure (PA) x CI product and the mean pulmonary artery pressure (PPA) x CI product, respectively. Only 23% of study animals demonstrated net transmyocardial lactate production during the septic study. When the infusion of sympathomimetics was accompanied by an increase in the PPA x CI and PA x CI products, a further increase in both Q-RV and Q-LV, respectively, occurred. Also, neither the ventricular endocardial-to-epicardial flow ratios nor transmyocardial lactate extraction were modified by the sympathomimetics infusion. We conclude that the septic response to infection in this animal model was not accompanied by significant abnormalities in the metabolic regulation of myocardial QO2 (R. E. Cunnion, G. L. Scher, and M. M. Parker, Circulation 73: 637-644, 1986).

Youth as a prognostic factor in carcinoma of the cervix: a matched analysis.

A matched analysis comparing 250 patients less than 35 years old with squamous cell cancer of the cervix treated between 1971 and 1981 to a randomly selected group matched on treatment who were greater than 35 years old was performed. A chart review that focused on important prognosticators for survival and progression-free interval was performed. The groups were found to be similar for the important prognosticators. Overall survival and progression-free intervals were plotted using Kaplan-Meier curves and demonstrated that for advanced stages, younger patients were less likely to survive and more likely to recur. Cox proportional-hazard analyses were performed, looking at important prognosticators of survival and progression-free interval. Age, stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of survival, while stage, positive lymph nodes, and cervical diameter emerged as statistically significant predictors of progression-free interval. The plot of relative hazard by stage of younger versus older patients showed an interaction between age and stage that merits further exploration.

Effect of PGE1 on altered distribution of regional blood flows in hyperdynamic sepsis.

Since the sepsis syndrome is associated with depressed vascular reactivity, it may be incorrect to assume that pharmacologically mediated changes in cardiac output will be proportionately distributed at the regional level of the circulation. We examined the effect of hyperdynamic sepsis and the concurrent administration of the vasodilatory prostaglandin (PGE1) on the regional distribution of blood flows (Q) in unanesthetized sheep rendered septic by cecal ligation and perforation. Systemic Q progressively increased throughout a 48-h study period after cecal ligation and perforation. Simultaneously, organ Q, measured by the radioactive microsphere technique, was depressed to the pancreas, but increased to the heart, gallbladder, brain, and colon; the increased Q to both heart and gallbladder was greater than the simultaneous increase in systemic Q in this septic study. With the infusion of PGE1 (1 microgram/kg/min), mean arterial perfusing pressures fell, while the cardiac index increased further over that recorded during the 48-h septic study. Despite this depression in arterial pressures, the only significant effect of PGE1 on the interorgan distribution of Q was in the renal circulation, where it was demonstrated that kidney Q fell. We conclude that (1) hyperdynamic and normotensive sepsis exerted nonhomogeneous effects on the distribution of organ Q, and (2) an increased systemic Q during PGE1 infusion was proportionately distributed to all organs, except the kidneys, where Q paradoxically fell. The latter finding suggests that the regulation of kidney Q may be depressed across the normal range of arterial perfusing pressures in the sepsis syndrome. Further investigation is essential to understand the effect of clinical interventions on the control of tissue O2 flux at both the regional and microregional levels of the circulation.

Splenectomy in gynecologic oncology: indications, complications, and technique.

Although uncommonly performed in this setting, splenectomy is sometimes indicated in patients with gynecologic malignancies. From January 1970 through March 1989, 45 patients at The University of Texas M.D. Anderson Cancer Center underwent splenectomy during the course of gynecologic laparotomies. All procedures were performed by the gynecology staff and trainees. Twenty-seven patients (60%) had ovarian cancer; endometrial and cervical cancers were present in three patients each. The remaining 11 patients had other diseases. Splenectomy was planned preoperatively in only 9 patients (20%). Thirteen patients (29%) underwent splenectomy because of injury to the spleen. Injury was most commonly due to traction during omentectomy, resulting in capsular laceration. The injury was immediately recognized in 12 patients; 1 patient required reexploration for hemoperitoneum. In 24 patients (53%), splenectomy was performed for tumor reduction. Pathologic examination showed that 11 of 24 patients had capsular involvement by tumor, 7 had parenchymal metastases, and 6 had no direct splenic involvement. Residual tumor following cytoreduction was smaller than 2 cm in 62.5% of patients. Splenectomy is a well-tolerated procedure and the operative approach can be tailored to the clinical situation and distribution of tumor. An attempt should be made to repair splenic injury when tumor involvement is not present.