Oxidative stress in critical care and vitamins supplement therapy: "a beneficial care enhancing".

OBJECTIVE: Critical illnesses are a significant public health issue because of their high rate of mortality, the increasing use of the Intensive Care Units and the resulting healthcare cost that is about 80 billion of dollars per year. Their mortality is about 12% whereas sepsis mortality reaches 30-40%. The only instruments currently used against sepsis are early diagnosis and antibiotic therapies, but the mortality rate can also be decreased through an improvement of the patient's nutrition. The aim of this paper is to summarize the effects of vitamins A, B, C and E on the balance between pro-oxidants and anti-oxidants in the critical care setting to confirm "a beneficial care enhancing". MATERIALS AND METHODS: The peer-reviewed articles analyzed were selected from PubMed databases using the keywords "critical care", "intensive care", "critical illness", "sepsis", "nutritional deficiency", "vitamins", "oxidative stress", "infection", and "surgery". Among the 654 papers identified, 160 articles were selected after title and abstract examination, removal of duplicates and of the studies on pediatric population. Finally, only the 92 articles relating to vitamins A, C, E and the B complex were analyzed. RESULTS: The use of vitamins decreased morbidity and mortality in perioperative period and critically ill patients, especially in ICU. Among the most encouraging results, we found that the use of vitamins, both as monotherapy and in vitamins combinations, play a crucial role in the redox balance. Vitamins, especially vitamins A, C, E and the B complex, could help prevent oxidative damage through the breakdown of the oxidizing chemical chain reaction. CONCLUSIONS: Even if the results of the studies are sometimes discordant or inconclusive, the current opinion is that the supplementation of one or more of these vitamins in critically ill patients may improve their clinical outcome, positively affecting the morbidity and the mortality. Further, randomized studies are required to deeply understand the potentiality of a vitamin supplementation therapy and develop homogeneous and standardized protocols to be adopted in every critical care scenario.

Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients.

PURPOSE: To evaluate our long-term experience with patients treated uniformly with radical cystectomy and pelvic lymph node dissection for invasive bladder cancer and to describe the association of the primary bladder tumor stage and regional lymph node status with clinical outcomes. PATIENTS AND METHODS: All patients undergoing radical cystectomy with bilateral pelvic iliac lymphadenectomy, with the intent to cure, for transitional-cell carcinoma of the bladder between July 1971 and December 1997, with or without adjuvant radiation or chemotherapy, were evaluated. The clinical course, pathologic characteristics, and long-term clinical outcomes were evaluated in this group of patients. RESULTS: A total of 1,054 patients (843 men [80%] and 211 women) with a median age of 66 years (range, 22 to 93 years) were uniformly treated. Median follow-up was 10.2 years (range, 0 to 28 years). There were 27 (2.5%) perioperative deaths, with a total of 292 (28%) early complications. Overall recurrence-free survival at 5 and 10 years for the entire cohort was 68% and 66%, respectively. The 5- and 10-year recurrence-free survival for patients with organ-confined, lymph node-negative tumors was 92% and 86% for P0 disease, 91% and 89% for Pis, 79% and 74% for Pa, and 83% and 78% for P1 tumors, respectively. Patients with muscle invasive (P2 and P3a), lymph node-negative tumors had 89% and 87% and 78% and 76% 5- and 10-year recurrence-free survival, respectively. Patients with nonorgan-confined (P3b, P4), lymph node-negative tumors demonstrated a significantly higher probability of recurrence compared with those with organ-confined bladder cancers (P <.001). The 5- and 10-year recurrence-free survival for P3b tumors was 62% and 61%, and for P4 tumors was 50% and 45%, respectively. A total of 246 patients (24%) had lymph node tumor involvement. The 5- and 10-year recurrence-free survival for these patients was 35%, and 34%, respectively, which was significantly lower than for patients without lymph node involvement (P <.001). Patients could also be stratified by the number of lymph nodes involved and by the extent of the primary bladder tumor (p stage). Patients with fewer than five positive lymph nodes, and whose p stage was organ-confined had significantly improved survival rates. Bladder cancer recurred in 311 patients (30%). The median time to recurrence among those patients in whom the cancer recurred was 12 months (range, 0.04 to 11.1 years). In 234 patients (22%) there was a distant recurrence, and in 77 patients (7%) there was a local (pelvic) recurrence. CONCLUSION: These data from a large group of patients support the aggressive surgical management of invasive bladder cancer. Excellent long-term survival can be achieved with a low incidence of pelvic recurrence.

Echocardiographic assessment of coronary blood flow velocity during controlled hypotensive anesthesia with nitroglycerin.

OBJECTIVE: To determine the effect of nitroglycerin on coronary blood flow velocity during controlled hypotensive anesthesia in humans. DESIGN: Internally controlled prospective study. SETTING: Single university hospital. PARTICIPANTS: Twenty American Society of Anesthesiologists class I and II patients undergoing general anesthesia for surgical resection of a malignancy. INTERVENTIONS: General anesthesia was induced with thiopental, fentanyl, and succinylcholine and maintained with isoflurane and vecuronium. Transesophageal echocardiography was used to evaluate left ventricular wall motion and blood flow velocity in the left anterior descending coronary artery. Intravenous nitroglycerin was used to reduce systolic arterial pressure to 60 to 70 mmHg. Intravenous albumin 5% was administered to maintain pulmonary capillary wedge pressure >5 mmHg. MEASUREMENTS AND MAIN RESULTS: The left anterior descending coronary artery was visualized clearly in 16 of 20 patients. At a mean nitroglycerin dose of 16+/-14 microg/kg/min, peak diastolic left anterior descending flow velocity increased significantly from 32.5+/-10.3 cm/sec to 44.7+/-14.6 cm/sec (p = 0.0103). None of the patients developed any ST-segment changes. CONCLUSIONS: During nitroglycerin-induced hypotensive anesthesia, coronary blood flow as assessed by peak diastolic left anterior descending flow velocity is preserved or increased in most patients. Increases in left anterior descending flow velocity are predictably achieved only at nitroglycerin doses >5 microg/kg/min. Intraoperative transesophageal echocardiography is useful in monitoring coronary flow velocity responses to controlled hypotensive anesthesia.

Invasive and noninvasive haemodynamic monitoring of acutely ill sepsis and septic shock patients in the emergency department.

The objective of this study was to describe early circulatory events of patients presenting to the emergency department (ED) with severe sepsis or septic shock. Invasive and noninvasive monitoring were used to evaluate sequential patterns of both central haemodynamics and peripheral tissue perfusion/oxygenation and to test the hypothesis that increased cardiac output is an early compensation to increased body metabolism. This is a prospective observational study of 45 patients who entered the ED with severe sepsis or septic shock in an urban academic ED. Invasive clinical monitoring was performed using a radial artery catheter and a thermodilution pulmonary artery catheter. Noninvasive monitoring consisted of an improved thoracic electrical bioimpedance device to estimate cardiac output; pulse oximetry for arterial saturation to reflect changes in pulmonary function, and transcutaneous oxygen (PtcO2) and carbon dioxide tensions (PtcCO2) as a reflection of tissue perfusion. Survivors had higher cardiac index, mean arterial pressure (MAP), and better tissue perfusion as measured by PtcO2, oxygen delivery, and oxygen consumption. Oxygen extraction ratio was higher in the nonsurvivors (p < 0.05) and there were episodes of high PtcCO2 values in the nonsurvivors. No significant differences were found in the heart rate, PAOP (wedge pressure) and SaO2 by pulse oximetry between the two groups. It is concluded that ED monitoring septic patients provides a unique opportunity to document early physiologic interactions between cardiac, pulmonary, and tissue perfusion functions in surviving and nonsurviving patients with septic shock. The data is consistent with the concept that increased cardiac output is an early compensatory response to increased body metabolism. Real time haemodynamic monitoring of patients in the ED provides early warning of outcome and may be used to guide therapy.

Intraoperative evaluation of tissue perfusion in high-risk patients by invasive and noninvasive hemodynamic monitoring.

OBJECTIVE: Although invasive monitoring has not been effective in late stages after organ failure has occurred, early postoperative monitoring revealed differences in survivor and nonsurvivor patterns and provided goals for improving outcome. We searched for the earliest divergence of survivor and nonsurvivor circulatory changes as an approach to earlier preventive therapy. The aim was to describe the intraoperative time course of circulatory dysfunction in survivors and nonsurvivors among high-risk elective surgery patients using both the thermodilution pulmonary artery catheter (PAC) and multicomponent noninvasive monitoring. DESIGN: Prospective intraoperative description of circulatory dysfunction. SETTING: University-run county hospital. PATIENTS: Two hundred nine consecutively monitored high-risk elective surgery patients. MEASUREMENTS AND MAIN RESULTS: We evaluated the data of high-risk elective surgery patients using both PAC and multicomponent noninvasive monitoring. The latter consisted of the following: a) an improved bioimpedance method for estimating cardiac output; b) the standard pulse oximetry to screen for pulmonary problems; c) transcutaneous oxygen and carbon dioxide tension sensors to evaluate tissue perfusion; and d) routine noninvasive blood pressure and heart rate. The current noninvasive impedance cardiac output estimations closely approximated those of the thermodilution method; r2 = .74, p < .001; the precision and bias was -0.124 +/- 0.75 L/min/m2. Outcome measures included intraoperative description of circulatory patterns of high-risk surgical patients who survived compared with nonsurvivors. Hypotension, low cardiac index, arterial hemoglobin desaturation, low transcutaneous oxygen, high transcutaneous carbon dioxide tensions, low oxygen delivery, and low oxygen consumption developed intraoperatively gradually over time; the abnormalities were more pronounced in the nonsurvivors than in the survivors. CONCLUSIONS: The survivors had slightly higher mean arterial pressure, cardiac index, and mixed venous oxygen saturation, as well as significantly higher oxygen delivery, oxygen consumption, transcutaneous oxygen tension, and transcutaneous oxygen tension/FIO2 ratios, than did the nonsurvivors. The data suggest that blood flow, oxygen delivery, and tissue oxygenation of the nonsurvivors became inadequate toward the end of the operation. Noninvasive monitoring provides similar information to that of the PAC; both approaches revealed low-flow and poor tissue perfusion that were worse in the nonsurvivors. The continuous on-line real-time displays of hemodynamic trends facilitate early recognition of acute circulatory dysfunction.

Hemodynamic patterns of survivors and nonsurvivors during high risk elective surgical operations.

Postoperative survivors' and nonsurvivors' hemodynamic and oxygen transport patterns have been extensively studied, and the early postoperative circulatory events leading to organ failures and death have been documented. Outcome was improved when potentially lethal circulatory patterns were treated during the early (the first 8-12 hours) postoperative period; but after the appearance of organ failure, reversal of nonsurvival patterns did not improve the outcome. The purpose of this study was to describe prospectively intraoperative circulatory deficiencies that precede shock, organ failures, and death. The ultimate aim was to elucidate nonsurvivor patterns at the earliest possible time to develop more effective preventive strategies for lethal organ failures. This approach is based on the assumption that it is easier and more effective to prevent the initiators of shock, such as hypovolemia, hypoxemia, poor tissue perfusion, and tissue hypoxia, than to treat the mediators of organ failure, such as cytokines, antigens, eicosinoids, and heat shock proteins. We monitored 356 high risk elective surgical patients with preoperative and intraoperative hemodynamic monitoring by the pulmonary artery (PA) thermodilution catheter. The conventionally monitored mean arterial pressure and heart rate remained in the normal range in both groups; the nonsurvivor pattern included decreased cardiac index, stroke index, stroke work, oxygen delivery, and oxygen consumption. Low oxygen consumption was partly compensated by increased oxygen extraction rates, and arterial pressures were maintained by increasing systemic vascular resistance. The early temporal pattern of nonsurvivors' changes were similar to those described during the postoperative period that preceded development of organ failure and death. This suggests that lethal circulatory dysfunctions may begin during the intraoperative period but become more apparent before and after organs fail during later postoperative stages.