Multiple organ failure--the discrepancy between our scientific knowledge and understanding and the management of our patients.

The excitement of molecular biology and of genetic knowledge and their possibilities must be balanced against our limitations in using this information for the care of our patients. There is a great discrepancy between what we know and what we can do. There are many reasons for this. A major one is that science must simplify/reduce the variables in experimentation and then generalize in terms of a specific factor or effect, whereas patients are complex with variables that we do not yet understand completely. This powerful science is now teaching us about the genetic diversity in both susceptibility and outcome of disease, and the diversity in life experiences and antigen exposures. Clinicians have tried to lump together and treat in a similar way many diverse human diseases. This has not worked well. Pancreatitis and perforated diverticulitis both produce inflammation and sepsis, but they are different processes and may both lead to multiple organ failure. This lumping together has contributed to the failure of so-called magic bullets. There are new contributors to organ damage. Gender, lifestyle and prior disease differences also complicate the care of patients. Despite this, we are slowly and gradually improving the care of our surgical patients by careful pre-, intra- and postoperative support and better, simpler and safer operations.

A debate on the subject "Are SIRS and MODS important entities in the clinical evaluation of patients?" The con position.

SIRS, MODS, and MOF are not diseases or even syndromes. They are simply clinical descriptors of people that are sick. They are symptoms and signs of various stages of illness progressing to death in the modern organ supporting ICU. They are catchy, popular acronyms but they cannot be treated specifically, and then only by support of organ functions. To help our patients and improve morbidity and mortality we must focus on specific diseases. Although ventilator associated pneumonia and pancreatitis may both produce an inflammatory response, cytokine-mediator activation and SIRS, they must each be treated in a different way. I believe that SIRS has led us astray.

A 32-year experience in 100 patients with giant paraesophageal hernia: the case for abdominal approach and selective antireflux repair.

BACKGROUND: Giant paraesophageal hiatal hernia (GPEH) presents a risk of catastrophic complications that include massive bleeding, strangulation, and perforation and should be repaired. Controversy persists as to the surgical approach and whether an antireflux repair is required. METHODS: This study reviews the experience with 100 patients with GPEH who underwent surgical repair between 1967 and 1999. Eighty patients underwent an elective operation, and 20 patients underwent an emergency procedure for complications of GPEH. The gastroesophageal junction was above the hiatus ("combined" hernia with sliding component) in 23 patients and in the abdomen in 77 patients, including 3 patients with a true parahiatal hernia. RESULTS: A thoracic approach was used in 18 patients, mostly early in our experience; postoperative gastric volvulus requiring transabdominal repair developed in 2 patients. The remaining 82 patients underwent an abdominal repair, with temporary gastrostomy to prevent gastric displacement in 75 patients; the hernial sac was resected, and the hiatus was reconstructed in all of the patients. Thirty-five patients with reflux on preoperative work up underwent a fundoplication, with gastroplasty in 2 patients because of a short esophagus. No patient has experienced hernia recurrence. Whereas symptomatic relief was excellent in all patients with elective repair, mild reflux was present in 2 patients after emergency operation. There were no deaths among the patients who underwent elective operation; there were 2 hospital deaths among those patients who underwent emergency operation (10%). CONCLUSIONS: GPEH should be repaired soon after recognition. Reflux should be evaluated before the operation, and if present, fundoplication should be part of the repair along with the reduction of the hernia, excision of the sac, gastropexy, and crural closure. These are best achieved with an abdominal approach.

T-cell reactivity and its predictive role in immunosuppression after burns.

OBJECTIVE: To obtain further insight into the constitutional, phenotype-dependent changes of T-helper-1 and T-helper-2 signature lymphokine synthesis after trauma. DESIGN: Prospective, descriptive study. SETTING: Intensive care unit of a burn center in a community hospital. PATIENTS: Ten patients 1, 3, 5, and 7 days after major burn injury and 15 healthy individuals. INTERVENTIONS: Peripheral blood mononuclear cells were separated and incubated (5 hrs) for cytokine production induced by the accessory cell-independent stimulus of ionomycin and phorbol 12-myristate 13-acetate. After fixation and permeabilization, cell samples were immunofluorescently stained for cell surface antigens (CD4 and CD8), intracellular interferon (IFN)-gamma, and interleukin (IL)-4 synthesis. Results were correlated with corresponding enzyme-linked immunosorbent assay measurements of the culture supernatants. MEASUREMENTS AND MAIN RESULTS: The phenotypic analysis of the composition of the helper (CD4) and suppressor/cytotoxic (CD8) T-cell subset demonstrated that patients suffering from major burns and healthy controls express these antigens in similar percentages. The ratio of CD4 positive to CD8 positive/CD16 negative T-cell subsets showed no significant changes after trauma compared with controls. The production of IL-4 was excessively up-regulated while the release of IFN-gamma was only slightly increased. The predominant cell source of IL-4 after burn trauma was the CD8+ cell with nearly five-fold increased production on day 5 (7.2+/-2.6%) vs. 1.5+/-0.4% in controls. While CD8+ cells are also capable of enhancing their IFN-gamma synthesis under stress by about 60% due to the significant participation of the naive CD45RA+ subset, the CD4+ IFN-gamma release remained largely unchanged. With this study, we demonstrated that in nonsurvivors the number of CD8+ IL-4-producing cells was significantly higher compared with controls; also, the number of IFN-gamma-releasing memory/effector CD45RO+ cells was lower compared with survivors. CONCLUSIONS: In previous experiments, we show that a shift to T(H)2 dominated phenotypes increases the risk for postburn infection. The current study confirms that major burns induce a significant shift of cytokine response in the T(H)2 direction and demonstrates that the CD8+, rather than the CD4+ phenotype, is present. Increased IL-4 production is associated with the T(H)2 lymphocyte. These diagnostic tests may help to differentiate patients with compensatory anti-inflammatory response syndrome and immunosuppression from those patients in the proinflammatory state associated with the systemic inflammatory response syndrome. The profile described in this article is associated with immunosuppression and may contraindicate attempts at anti-inflammatory therapy for sepsis.

Systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), multiple organ failure (MOF): are we winning the battle?

The problems of inflammation and infection leading to organ dysfunction and failure continue to be the major problems after injury and operations and with intensive care for many diseases and problems. When SIRS goes to MODS and MOF, the mortality becomes high, ranging from 30-80% depending on the number of failed organs. In spite of this, there have been recent exciting discoveries and contributions to patient care. A reasonable question then is, are we making progress and if so, can we document it? Are the incidence and mortality of MOF decreasing? The literature comparing care over some years suggests a decrease in ICU mortality in patients with severe organ failure, a decrease in elective surgical mortality, and improvement in the results of care and outcome for trauma patients. Review of problems occurring in sick and injured patients indicates that certain problems are decreasing in frequency, such as renal failure and ARDS after trauma, stress gastrointestinal bleeding, and abdominal abscesses, and these should improve outcome. There are a number of exciting therapies that help certain patients but not everyone. These controversies challenge us to focus on where and when there are positive benefits. Risk factors for MOF are addressed to focus on early intervention. The possibilities of multiple therapeutic agents are described. Finally, we describe and emphasize our recommendation to strive to prevent MODS and SIRS.

Multiple organ failure, multiple organ dysfunction syndrome, and systemic inflammatory response syndrome. Why no magic bullets?

The concept of multiple organ failure and related abnormalities was first developed in the 1970s. Multiple organ failure became evident when the support systems in intensive care units were able to keep patients alive long enough for multiple organ problems to develop in them. The high mortality of patients with multiple organ failure provided a focus for the problems that ultimately led to death for many patients in the intensive care unit. The frequency of infection, sepsis, or inflammation in producing multiple organ failure led to clinical trials of so-called magic bullets for the treatment of patients with sepsis. These trials have had either limited success or negative results, despite considerable evidence for efficacy or protection by such agents in experimental animals and in studies of normal human volunteers. I believe a major reason for these negative results has been the use of general entry criteria for the trials rather than the treatment of specific diseases or injuries.

The use of oxygen consumption and delivery as endpoints for resuscitation in critically ill patients.

OBJECTIVE: Oxygen consumption (VO2I) and delivery (DO2I) indices have been stated to be superior to conventional parameters as endpoints for resuscitation. However, another interpretation of published data is that inability to increase VO2I/DO2I given adequate volume resuscitation reflects inadequate physiologic reserve and poor outcome. DESIGN: Fifty-eight critically ill patients were randomized to two groups. In group 1 (27 patients) attempts were made to maintain VO2I > or = 150 or DO2I > or = 600 mL/min/m2. If DO2I was > 600, no attempt was made to increase VO2I even if it was < 150. Group 2 (31 patients) was resuscitated based on conventional parameters. Volume resuscitation protocols and goals for pulmonary capillary wedge pressure were the same in both groups. VO2I/DO2I were recorded in group 2, but physicians were blinded to this data. Age, Injury Severity Score, and Acute Physiology and Chronic Health Evaluation (APACHE II) score were not different between groups. MAIN RESULTS: Three patients in group 1 and two patients in group 2 died of organ failure (OF). One additional patient in group 2 died of refractory shock within 24 hours. Two of the patients in group 1 who died failed to meet VO2I/DO2I goals within 24 hours despite maximal resuscitation. Mortality was not different between the groups even with exclusion of the group 1 patients who failed to meet VO2I/DO2I goals (p = 0.66). After exclusion of the patient in group 2 who died of refractory shock, OF occurred in 18 of 27 (67%) in group 1 and in 22 of 30 (73%) in group 2 (p = 0.58). Length of ventilator support, intensive care unit stay, and hospital stay were not different between groups. When all patients were assessed, no difference was found in the incidence of OF between patients who attained the VO2I goal and those who did not. OF occurred in 20 of 34 (59%) patients who maintained a mean DO2I > or = 600 during the first 24 hours of the study and in 21 of 24 (88%) of those who did not (p < 0.02). CONCLUSIONS: No difference was found in the incidence of OF or death in patients resuscitated based on oxygen transport parameters compared to conventional parameters. These data suggest that given adequate volume resuscitation, oxygen-based parameters are more useful as predictors of outcome than as endpoints for resuscitation.

Clinical trials of new and novel therapeutic agents.

Throughout this issue of World Journal of Surgery are recommendations and descriptions of therapy to prevent the development of multiple organ failure (MOF). The subjects include advances in monitoring; circulatory, pulmonary, and gut support; blood treatment; immune modulation; and control of the inflammatory process. Additional methods of organ support include recommendations for resuscitation and initial care and for early definitive operations. New therapeutic agents such as growth factors, glucan, ketaconazole, and antithrombin III are described. Finally, methods to support organ function before it fails (circulation, lungs, and kidneys) are described.

Trauma management in the 21st century.

Predicting the future can be interesting but difficult, particularly because of the exciting developments in the science of injury, inflammation, sepsis, and shock. Considering what has happened between 1895-1995, it is difficult to contemplate what will happen in the next 100 years. Will change accelerate in the 21st century? So far, our scientific knowledge and capability have exceeded the ability to care for injured and operated patients. Much of the future will depend upon society's ability to control violence and prevent injury. Most of the factors resulting in death after injury are beyond the control of those caring for patients or those studying patient problems. Thus the major risk factors for death after trauma are injury severity, the age of the patient, the problems of shock, and end-stage organ injury. If we are to decrease mortality from injury, we must work to prevent injury and decrease the severity of injury while improving our capabilities to care for the injured. New rapid diagnostic procedures, immediate therapy at the scene of the injury, portable or flying resuscitative and therapeutic units, and better understanding of the need for the inflammatory response in contrast to the disaster produced by an overwhelming inflammatory response will help. The major hazard for predicting the future in the management of injured patients could be predicting that something cannot be done. We recognize now that almost anything can be done if we learn enough and understand the problems sufficiently well. The Shock Society is dedicated to that purpose.

Multimodality therapy for adenocarcinoma of the esophagus.

Few reports exist detailing results of multimodality treatment for adenocarcinoma of the esophagus. We have treated 28 such patients using a preoperative regimen consisting of two courses of cisplatin and 5-fluorouracil with radiation (either 3,000 or 3,600 cGy). There were 25 men and 3 women (mean age, 62.9 years; range, 35 to 86 years), and 16 patients were known to have Barrett's esophagus. Dysphagia was present for a mean of 2.7 months, and the average weight loss was 6.5 kg. Tumors ranged from 2 to 10 cm in length (mean, 5.2 +/- 1.8 cm) with American Joint Committee on Cancer clinical stage I in 2 patients, stage II in 19 patients, and stage III in 7. Dysphagia improved in 23 patients (82%), and in 8 (29%) no tumor was detected during radiologic and endoscopic staging after neoadjuvant therapy. Four patients refused operation. Esophagectomy via standard Ivor Lewis approach was accomplished in 20 of 24 patients (87%) undergoing operation. There were no operative deaths, and mean hospital stay was 15.5 +/- 11.6 days. Four patients (17%) were complete responders with no tumor in the resected specimen. Actuarial survival in the 28 patients at 1, 2, and 3 years is 71%, 28%, and 20% respectively. Of the 20 esophagectomy patients, 6 are alive with no evidence of disease at 10, 50, 54, 70, 77, and 84 months. Three of these were complete responders. Only 1 of the 8 patients no undergoing resection is alive at 16 months with no evidence of disease after further radiotherapy and chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)