Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine

OBJECTIVE: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score in assessing the incidence and severity of organ dysfunction in critically ill patients. DESIGN: Prospective, multicenter study. SETTING: Forty intensive care units (ICUs) in 16 countries. PATIENTS: Patients admitted to the ICU in May 1995 (n = 1,449), excluding patients who underwent uncomplicated elective surgery with an ICU length of stay <48 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The main outcome measures included incidence of dysfunction/failure of different organs and the relationship of this dysfunction with outcome. In this cohort of patients, the median length of ICU stay was 5 days, and the ICU mortality rate was 22%. Multiple organ dysfunction and high SOFA scores for any individual organ were associated with increased mortality. The presence of infection on admission (28.7% of patients) was associated with higher SOFA scores for each organ. The evaluation of a subgroup of 544 patients who stayed in the ICU for at least 1 wk showed that survivors and nonsurvivors followed a different course. This subgroup had greater respiratory, cardiovascular, and neurologic scores than the other patients. In this subgroup, the total SOFA score increased in 44% of the nonsurvivors but in only 20% of the survivors (p < .001). Conversely, the total SOFA score decreased in 33% of the survivors compared with 21% of the nonsurvivors (p < .001). CONCLUSIONS: The SOFA score is a simple, but effective method to describe organ dysfunction/failure in critically ill patients. Regular, repeated scoring enables patient condition and disease development to be monitored and better understood. The SOFA score may enable comparison between patients that would benefit clinical trials.     

Increased circulating thrombomodulin in children with septic shock

OBJECTIVES: To test the hypothesis that children diagnosed with septic shock have increased plasma thrombomodulin values as a manifestation of microcirculatory dysfunction and endothelial injury; to determine whether plasma thrombomodulin concentrations are associated with the extent of multiple organ system failure and mortality. DESIGN: Prospective, cohort study. SETTING: Pediatric intensive care unit. PATIENTS: Twenty-two children with septic shock and ten, healthy, control children. INTERVENTIONS: Blood samples were obtained for plasma thrombomodulin determinations every 6 hrs for 72 hrs in septic shock patients and once in healthy control patients. MEASUREMENTS AND MAIN RESULTS: Thirty-two children (22 septic shock, and 10 healthy controls) were enrolled in the study. Thrombomodulin concentrations were determined by an enzyme-linked immunosorbent assay. Septic shock nonsurvivors had significantly greater mean thrombomodulin concentrations (10.6 +/- 2.2 ng/mL) than septic shock survivors (5.5 +/- 0.6 ng/mL) (p < .05) and healthy control patients (3.4 +/- 0.2 ng/mL) (p < .01). Mean thrombomodulin values increased as the number of organ system failures increased. CONCLUSIONS: Pediatric survivors and nonsurvivors of septic shock have circulating thrombomodulin concentrations 1.5 and 3 times greater than healthy control patients. These findings likely represent sepsis-induced endothelial injury. Patients with multiple organ system failure have circulating thrombomodulin concentrations which are associated with the extent of organ dysfunction. We speculate that measurement of plasma thrombomodulin concentrations in septic shock may be a useful indicator of the severity of endothelial damage and the development of multiple organ system failure.     

Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure

OBJECTIVE: This study investigates the course of serum cytokine levels in patients with multiple trauma, patients with a ruptured abdominal aortic aneurysm (AAA), and patients undergoing elective AAA repair and the relationship of these cytokines to the development of adult respiratory distress syndrome (ARDS) and multiple organ failure (MOF). SUMMARY BACKGROUND DATA: Severe tissue trauma, hemorrhagic shock, and ischemia-reperfusion injury are pathophysiologic mechanisms that may result in an excessive uncontrolled activation of inflammatory cells and mediators. This inflammatory response is thought to play a key role in the development of (remote) cell and organ dysfunction, which is the basis of ARDS and MOF. METHODS: The study concerns 28 patients with multiple trauma, 20 patients admitted in shock because of a ruptured AAA, and 18 patients undergoing elective AAA repair. Arterial blood was serially sampled from admission (or at the start of elective operation) to day 13 in the intensive care unit, and the serum concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, and IL-6 were determined. RESULTS: Twenty-two patients died, 15 within 48 hours and 7 after several weeks, as a result of ARDS/MOF. At hospital admission and after 6 hours, these nonsurvivors had significantly higher plasma TNF-alpha and IL-1 beta levels than did the survivors. At the same measuring points, TNF-alpha and IL-1 beta were significantly more elevated in patients with ruptured AAA than in traumatized patients. However, IL-6 was significantly higher in the traumatized patients. In 10 patients, ARDS/MOF developed, and 41 had an uncomplicated course in this respect. Those with ARDS/MOF exhibited significantly different cytokine patterns in the early postinjury phase. TNF-alpha and IL-1 beta levels were higher mainly on the first day of admission; IL-6 concentrations were significantly elevated in patients with ARDS/MOF from the second day onward. The latter cytokine showed a good correlation with the daily MOF score during the whole 2-week observation period. CONCLUSIONS: In the early postinjury phase, higher concentrations of these cytokines are associated, not only with an increased mortality rate, but also with an increased risk for subsequent ARDS and MOF. These data therefore support the concept that these syndromes are caused by an overwhelming autodestructive inflammatory response.     

Hormonal changes and pituitary histological and immunocytochemical studies of patients with multiple organ failure

OBJECTIVE: We investigated the correlation between the endogenous hormonal changes of pituitary-adrenal and pituitary-thyroid hormones and the prognosis of patients in multiple organ failure, and elucidated the mechanism of blunted thyrotropin (TSH) secretion by histological and immunocytochemical studies of anterior pituitary glands. PATIENTS: Forty-three patients were studied who had been admitted to the intensive care unit of Sapporo Medical University Hospital and had been diagnosed as having multiple organ failure. MEASUREMENTS: Pituitary adrenal hormones [corticotropin (ACTH), cortisol] and pituitary thyroid hormones [TSH, triiodothyronin (T3), free-T3, thyroxine (T4), free-T4, thyroxine-binding globulin (TBG)] were measured, and TSH and prolactin (PRL) responses thyrotropin-releasing hormone (TRH) were examined within 24 hours of admission to the ICU. Individual variables were compared between survivors (n = 19) and nonsurvivors (n = 24). Thirteen patients (five survivors, eight nonsurvivors) were investigated again before discharge from the ICU or death. Morphology was examined by hematoxilin-eosin staining, and avidin-biotin-peroxidase complex immunostaining was used to demonstrate the spectrum of TSH in 14 nonsurvivors. RESULTS: (1) ACTH levels remained within the normal range, while cortisol levels increased to above normal levels. Neither hormone showed significant differences between survivors and nonsurvivors. In nonsurvivors, cortisol levels decreased before death despite the increased ACTH levels. (2) T3 and free-T3 levels decreased markedly to below normal values, and reverse-T3 levels increased markedly to above normal values. Nonsurvivors showed significant differences in TSH, T4 and reverse-T3 levels compared with survivors. (3) TSH response to TRH was blunted in both groups but PRL response to TRH was normal. Nonsurvivors showed severely depressed TSH response. Nonsurvivors continued to show blunted TSH response to TRH, while this improved in survivors. (4) The histological study did not show very serious damages to anterior pituitary glands as TSH secretion was depressed. Many TSH immunoreactive cells were also observed by immunocytochemical study. CONCLUSION: Decreased cortisol, low T4 levels and blunted TSH response to TRH correlated with mortality in MOF patients. Histological and immunocytological studies suggest that blunted TSH secretion is not caused by pituitary damages or TSH exhaustion but by disturbances in TSH secretion. This blunted TSH secretion is reversible and its improvement is an indicator of survival.     

Outcome of blunt thoracic aortic injury in a level I trauma center: an 8-year review

BACKGROUND: The purpose of this study was to evaluate our experience with blunt thoracic aortic injury and identify factors predictive of outcome. METHODS: Hospital charts, trauma registry data, and autopsies of 64 patients with blunt thoracic aortic injury from 1988 to 1995 were reviewed. RESULTS: Patients were identified and segregated based on admission physiology. Group 1 patients (n = 19) arrived in arrest. Group 2 patients (n = 10) arrived in shock with systolic BP 90. Group 3 patients (n = 35) arrived with systolic BP>90. All patients in groups 1 and 2 expired. Injury Severity Scores for nonsurvivors in group 3 (n = 12) were significantly higher than survivors. There were no significant differences when comparing time of injury to repair or arrival between groups, or in mortality or paralysis comparing repair techniques or clamp/bypass times. Double lumen endotracheal tubes caused significant operative delays compared to single lumen tubes. CONCLUSIONS: Predictors of survivability were hemodynamic stability on arrival and lower Injury Severity Scores. In thoracic aortic injury patients arriving hemodynamically stable, Injury Severity Score correlated with mortality but not paralysis.     

Measurement of lung volume and DLCO in acute respiratory failure

We have undertaken rebreathing measurements of functional residual capacity (FRC), carbon monoxide diffusing capacity (DLCO), and diffusing coefficient (KCO) during positive pressure ventilation in 15 patients with adult respiratory distress syndrome (ARDS). Measurements of oxygenation (PaO2:FIO2 ratio) and lung injury score (LIS) were also recorded. Eight patients subsequently died (mortality of 53%). There was no significant difference in mean FRC, PaO2:FIO2, or LIS at presentation between survivors and nonsurvivors. However, both DLCO and KCO at presentation were significantly greater in survivors than nonsurvivors. In a separate study of nine patients with less severe lung injury, pulmonary capillary blood volume, derived from values of DLCO measured at two different values of FIO2, correlated with invasive pulmonary vascular resistance (PVR) measurements (r = 0.84, p < 0.01). DLCO measurements can be successfully undertaken in patients being ventilated with acute lung injury and may be a useful, noninvasive method of assessing the pulmonary circulation. The lowest values of DLCO were recorded in patients who subsequently did not survive.     

Exercise and oxygen inhalation in relation to prognosis of chronic obstructive pulmonary disease

We examined the relationship between prognosis and arterial blood gases during exercise and 100 percent oxygen inhalation in 54 patients randomly selected from 119 background patients with chronic obstructive pulmonary disease (COPD). Light exercise was performed and 100 percent oxygen was inhaled during clinically stable stages. By four years after these tests, 19/54 patients had died from respiratory failure. All subjects had similar physical and clinical features. Survivors had significantly higher PaO2 during air breathing than nonsurvivors; in nonsurvivors, FEV1 and MVV were significantly lower, and heart rate and RV/TLC were significantly higher. Exercise PaO2 of nonsurvivors decreased by 6.7 mm Hg, whereas that of survivors did not change. The P(A--a)O2 did not change in survivors and nonsurvivors during exercise, but in survivors it was significantly smaller. Mean PaO2 after 100 percent oxygen was significantly lower, and PaCO2 was significantly higher in nonsurvivors than in survivors, and in nonsurvivors the increase in PaO2 during 100 percent oxygen correlated positively with the time between first admission and death. These results indicate that patients with combination of resting arterial hypoxemia, worsened hypoxemia during stepped-up exercise, and lesser degree of arterial oxygenation and increased PaCO2 during 100 percent oxygen inhalation may have a poor prognosis.     

Iliac vessel injury: operative physiology related to outcome

BACKGROUND: Fifty-three patients treated at a level I trauma center with iliac vessel injury were studied to determine if body temperature and acid-base status in the operating room predicts outcome. METHODS: Records were reviewed for demographics, mechanism of injury, body temperature, acid-base status, operative management, and outcome. Statistical methods included Student's t test, odds ratio determination, and chi-square analysis to determine statistical significance. RESULTS: Fifty-three patients (47 male, 6 female) sustained 92 iliac vascular injuries (36 arterial, 56 venous). Mortality was 34%, with 72% of deaths due to shock within 24 hours. Physiologic parameters differed significantly between survivors and nonsurvivors. Odds ratio identified six conditions; the number present predicted outcome. CONCLUSIONS: (1) There are significant differences between initial and final operating room temperature and acid-base status in survivors versus nonsurvivors with iliac vessel injury. Conditions for odds ratio can be calculated and correlated with outcome. (2) A patient with two or more conditions should be considered for an abbreviated laparotomy to allow for reversal of "physiologic failure."     

American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definitions of the systemic inflammatory response syndrome and allied disorders in relation to critically injured patients

OBJECTIVES: To determine the frequency of the proposed definitions for the systemic inflammatory response syndrome (SIRS), sepsis and septic shock, and to further define severe SIRS and sterile shock as determined at 24 hrs of admission to an intensive care unit (ICU) in critically ill trauma patients without head injury, and their relationships to mechanism of injury, Acute Physiology and Chronic Health Evaluation (APACHE) II score, risk of death, Injury Severity Score (ISS), number of organ failures, and mortality rate. DESIGN: Prospective, inception cohort analysis. SETTING: Sixteen-bed surgical ICU in a teaching hospital. PATIENTS: Four hundred fifty critically injured patients without associated head trauma. Penetrating trauma accounted for 70% (gunshot 202; stab 113) and nonpenetrating trauma for 30% (motor vehicle collision 103; blunt 32) of admissions. Three hundred ninety-four (88%) patients underwent surgical procedures. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Infective and noninfective insults were distinguished by the need for therapeutic or prophylactic antibiotics, respectively, based on an established antibiotic policy. Three hundred ninety-five (87.8%) patients fulfilled a definition of the SIRS criteria. The frequency of the definitive categories was SIRS 21.8%, sepsis 14.4%, severe SIRS 8.4%, severe sepsis 13.6%, sterile shock 9.3%, and septic shock 20.2%. Patients with penetrating trauma had a significantly higher frequency of sepsis, severe sepsis, and septic shock (p < .01). The APACHE II score, risk of death, and number of organ failures increased significantly in both infective and noninfective groups with increasing severity of the inflammatory response. Sterile shock was associated with a significantly higher APACHE II score (p < .02), risk of death (p < .01), and number of organ failures (p = .03) compared with septic shock. Only sterile shock was associated with a significantly higher ISS (p < .01). Organ system failure was significantly (p < .001) higher in nonsurvivors compared with survivors in all categories. The only significant (p < .001) difference in mortality rate was found between patients in shock and all other categories. CONCLUSIONS: The current definitions of SIRS, sepsis, and related disorders in critically injured patients without head trauma show a significant association with physiologic deterioration and increasing organ dysfunction. The only significant association with mortality, however, is the presence of shock. The definitions require refinement, with the possible inclusion of more objective gradations of organ system failure, if they are to be used for stratifying severity of illness in seriously injured patients.     

IL-12 is an effective adjuvant for induction of mucosal immunity

OBJECTIVE: To define those physiologic and clinical variables that have a positive or negative predictive value in discriminating survivors from nonsurvivors with traumatic injuries and a Trauma Score of 5 or less. METHODS: A retrospective review of 2,622 trauma patients transported by an air medical service from the scene of injury to a Level I trauma center was performed. Demographic, physiologic, and clinical variables were evaluated. RESULTS: One hundred thirty-six patients were studied; 14 patients survived trauma resuscitation. Survivors had statistically significant improvement in the Glasgow Coma Scale from the field to arrival in the emergency room. Revised Trauma Score, probability of survival, pulse, respiratory rate, cardiac rhythm, central nervous system activity, and signs of life were statistically more favorable in survivors. CONCLUSION: In patients who survived to discharge, signs of central nervous system activity in the field was a positive predictor of survival, and severe head injury served as a negative predictor of survival.     

Meningococcal septic shock in children: clinical and laboratory features, outcome, and development of a prognostic score

The clinical characteristics of and outcome for 75 children with meningococcal septic shock were studied. In addition, a new prognostic scoring system was developed. The median age of the patients was 3.2 years (range, 3 weeks to 17.9 years). The most common phenotype of Neisseria meningitidis was B:4:P1.4 (27%). A mortality rate of 21% was observed. Ten (17%) of the 59 survivors had serious sequelae. Calcium levels were significantly lower in patients with seizures. Disseminated intravascular coagulation occurred in 58% of the patients who were tested. Logistic regression analysis identified four laboratory features independently associated with mortality: serum C-reactive protein level, base excess, serum potassium level, and platelet count. These features were used to develop a novel scoring system with a predictive value for death and survival of 71% and 90%, respectively. The outcome was predicted correctly for 86% of the patients, which is higher than rates previously reported for scoring systems.     

Clinicopathologic features of patients with hepatocellular carcinoma surviving >10 years after hepatic resection

BACKGROUND: This study was performed to clarify the clinicopathologic features of hepatocellular carcinoma (HCC) patients surviving >10 years after hepatic resection. METHODS: Between January 1971 and April 1987, 142 patients underwent hepatic resection. Thirty-nine patients who died of surgical morbidity (surgical mortality rate: 27.5%) were excluded from this study. Among the 103 patients who survived and were observed for >10 years after surgery, 12 patients (11.7%) survived >10 years after hepatectomy. The surviving patients were divided into 2 groups: 10-year survivors (n = 12) and nonsurvivors (n = 91). A comparative study between the two groups was made. RESULTS: Preoperative liver function tests such as the indocyanine green retention test at 15 minutes and albumin levels showed that 10-year survivors had better liver function than nonsurvivors. With regard to virus markers, 5 of 12 patients (41.7%) were positive for hepatitis B surface antigen (HBs-Ag) and the incidence of hepatitis B virus-related HCC was significantly higher than in nonsurvivors (P = 0.020). The results also showed that 4 of 12 long term survivors had hepatitis C virus (HCV) antibody and 1 patient did not have any HCV antibody or HBs-Ag. In two other patients, the HCV antibody was not measured and HBs-Ag was negative. Among four patients with the HCV antibody, the serum HCV RNA concentration, measured by branched DNA probe assay, was <0.5 in 3 patients and 1.72 in 1 patient. Therefore, the HCV RNA concentration tended to be lower in 10-year survivors. Tumor recurrence occurred in 8 of the 10-year survivors. Solitary recurrence was observed in five patients whereas multiple recurrence was observed in three patients. All five patients with solitary recurrence underwent a second resection. CONCLUSIONS: Based on the results of the current study, good liver function, HBs-Ag positivity, and a low concentration of serum HCV RNA in HCV-related HCC should be considered potentially good predictors of a long term survival.     

Risk factors for chronic graft-versus-host disease after bone marrow transplantation: a retrospective single centre analysis

We retrospectively compared the changes in serum albumin concentration and colloid osmotic pressure between survivors and nonsurvivors of prolonged (> or = 7 days) critical illness over a 2-year period from 1 July 1995. All patients had serum albumin measured daily, and colloid osmotic pressure measured 5 days a week, throughout their ICU admission. They received crystalloid and colloid infusions as well as parenteral or enteral feeding. Infusions of albumin were not used to treat hypoalbuminaemia. One hundred and forty-five patients were included, 66 nonsurvivors and 79 survivors. Nonsurvivors were significantly older than survivors [mean (95% CI): 58 (3.8) and 49 (4.1) years, respectively] and had a greater risk of death [mean (95% CI): 0.44 (0.06) and 0.28 (0.05); p < 0.05]. There was no significant difference in gender, APACHE II score [mean (95% CI): 22 (2.7) (nonsurvivors); 18 (2.3) (survivors)] or length of stay [median (interquartile range): 14 (9-27) days (nonsurvivors); 15 (9-26) days (survivors)]. There was no difference between the two groups in the absolute minimum serum albumin concentrations reached, the time to reach that minimum or the minimum in the first 7 days. However, nonsurvivors had a significantly lower mean serum albumin concentration: [mean (95% CI): 15.7 (5.1) g.l-1 compared with 18.3 (4.6) g.l-1 in survivors; p < 0.05]. They also had a lower recovery mean (the weighted mean after the minimum value): [mean (95% CI): 13.3 (5.1) g.l-1 (nonsurvivors) and 18.6 (5.3) g.l-1 (survivors); p < 0.01]. Analysis of colloid osmotic pressure results showed no difference between the groups in mean, minimum or recovery mean. Regression analysis of mean colloid osmotic pressure and albumin revealed that albumin only contributed 17% of the colloid osmotic pressure in these patients. The similar decrease in albumin in nonsurvivors and survivors may reflect the acute inflammatory response and/or haemodilution. However, survivors showed an ability to increase serum albumin concentrations, possibly owing to resumption of synthesis. The colloid osmotic pressure varied little between or within either group of patients, possibly because of the use of artificial colloids. There was no relationship between death and colloid osmotic pressure.     

Periodontal repair in intrabony defects treated with a calcium carbonate implant and guided tissue regeneration

OBJECTIVE: To determine mortality and factors that might predict outcome in severe community-acquired pneumococcal pneumonia treated by a standard protocol. DESIGN: Prospective, non-concurrent study. SETTING: Respiratory intensive care unit (ICU) in a teaching hospital. PATIENTS: 63 patients who were diagnosed by positive blood culture or Gram stain and culture of sputum or tracheal aspirate were included. MEASUREMENTS AND RESULTS: Clinical features, severity scores including Acute Physiology and Chronic Health Evaluation (APACHE) II, organ failure and lung injury scores, and the clinical course in the ICU were documented; 79% of patients required mechanical ventilation. Bacteraemia was present in 34 patients (54%); there were no distinguishing clinical features between bacteraemic and non-bacteraemic cases. The overall mortality was 21%, with only 5 deaths (15% mortality) in the bacteraemic group. Shock and a very low serum albumin (< 26 g/l) were the only clinical features that differentiated survivors from non-survivors; lung injury, APACHE II and multiple organ failure scores were all predictive of outcome. The positive predictive value and specificity in predicting death in individuals for the modified British Thoracic Society rule 1 were 26 and 64%; APACHE II > 2057 and 88%; > 2 organ failure 64 and 92%; and lung injury > 233 and 73%, respectively. CONCLUSIONS: These results suggest that even in bacteraemic cases mortality should be below 25% with intensive care management and that conventional scoring systems, while predictive of group mortality, are unreliable in individuals.     

Plasma levels of glutathione, alpha-tocopherol and lipid peroxides in polytraumatized patients; evidence for a stimulating effect of TNF alpha on glutathione synthesis

Prognosis and outcome of polytraumatized patients are determined by the possible development of multiple organ failure (MOF). Among the direct traumatic organ damage, it is caused by a systemic inflammatory reaction. This might be triggered by an activation of the inflammatory mediator cascade following hemorrhagic-traumatic shock as well as by oxygen-derived free radicals (ROS). The aim of our present study was to answer the following questions: 1. Is the "oxidative stress" measurable during the development of MOF after polytraumatic injury? 2. Is there a relation between the activation of the inflammatory mediator cascade and changes of the organism's antioxidative system? The study group included 26 patients (15 survivors, 11 non-survivors) suffering from severe polytraumatic injury (Hannover Polytrauma Score 12-63 points). Plasma levels of reduced (GSH) and oxidized (GSSG) glutathione alpha-tocopherol (TOC), lipid peroxides (expressed in terms of thiobarbituric acid reagible substances = TBARS), and tumor necrosis factor alpha (TNF) were measured each day from the point of admission on the ICU until the discharge or death of the patients. The following results were obtained: Independent from the outcome, we observed a continuous loss of plasma sulfhydryl groups and TOC. In the patients developing a MOF score > 5 on 10th day after injury (n = 6), a significant increase in plasma GSSG level was measurable. Additionally, a total loss of plasma GSH was seen in some of these patients indicating the collapse of the GSH-dependent antioxidative system. Similar changes were never observed in patients with MOF score < or = 5 on 10th day after injury (n = 15). In this group, a significant correlation between plasma TNF peaks and short time GSH boosts was obtained as a possible indicative for a stimulating effect of TNF on GSH synthesis. It can be concluded that processes of oxidative stress in connection with a consumption of endogenic antioxidants might be able to promote the development of MOF after polytraumatic injury.     

Infected pancreatic necrosis complicated by multiple organ failure

BACKGROUND/AIMS: Sixteen patients with bacteriologically proven severe infected pancreatic necrosis (IPN) undergoing sequential surgical treatment were studied prospectively. METHODOLOGY: The severity of IPN was documented pre-operatively using the following scores: 1) degree of necrosis by CT scan [< 30% in three patients (19%); 30-50% in nine patients (56%); > 50% in four patients (25%)]; 2) Elebute and Stoner's sepsis score (16 +/- 4 points); 3) Goris' score of multiple organ failure (MOF) (5 +/- 2 points). Sequential surgical treatment was carried out by the same surgical team, as follows: 1) abdominal re-explorations through a zipper for the first 7-10 days; 2) open abdomen and repeated peritoneal debridements for the following 7-10 days; 3) continuous closed peritoneal lavage with multiple drainage, until resolution of infection (range: 15-85 days). No patient required further re-exploration. RESULTS: Mortality occurred in 3/16 patients (19%), due to MOF in all 3 cases. The 13 survivors (81%) were discharged convalescent with closed abdominal wound, feeding orally, after 73 +/- 33 days, without fistulae. These results indicate that by treating severe IPN with the technique of sequential abdominal re-explorations, open drainage and continuous closed lavage, a low 19% mortality can be achieved. CONCLUSION: This study provides an assessment of the pre-operative severity of sepsis and of MOF in each patient with IPN: these data could facilitate future comparison of results obtained with other treatment modalities.     

Natural cytokine antagonists and endogenous antiendotoxin core antibodies in sepsis syndrome. The Sepsis Intervention Group

OBJECTIVE: To assess the value of measuring circulating concentrations of mediators (endotoxin, tumor necrosis factor-alpha [TNF-alpha], interleukin-1 beta [IL-1 beta], and interleukin-6[IL-6]) and their endogenous antagonists (antiendotoxin core antibody [EndoCAb], interleukin-1 receptor antagonist [IL-1ra], and soluble TNF receptors [sTNF-R]) in predicting mortality and organ failure in sepsis syndrome. DESIGN: Cohort study with a follow-up period of 30 days. SETTING: Intensive therapy units of five tertiary referral centers in Scotland. SUBJECTS: A total of 146 intensive therapy unit patients with sepsis syndrome underwent repeated sampling during a 10-day period following admission to an intensive therapy unit. MAIN OUTCOME MEASURES: Circulating concentrations of mediators and antagonists were compared in survivors and nonsurvivors. RESULTS: Median Acute Physiology and Chronic Health Evaluation II score was 23 (range, 8 to 40). Mortality at 30 days was 49%. On entry to the study, circulating endotoxin was detected in 66% of patients, TNF-alpha in 14%, and IL-1 beta in 29%. Levels did not predict mortality or organ failure. Patients with IL-6 concentrations in excess of 3000 pg/mL had an increased mortality rate (64% vs 40%, P = .02). The incidence of IgG EndoCAb depletion on entry to the study was 26% in nonsurvivors and 10% in survivors (P = .02). Initial concentrations of both type I and type II sTNF-R were significantly higher in nonsurvivors (P < .01). Initial circulating IL-1ra concentrations were not of value in predicting mortality. Cytokine antagonists were present in concentrations 30- to 100,000-fold greater than their corresponding cytokine. CONCLUSION: The observed high circulating levels of the cytokine antagonists IL-1ra and sTNF-R and the relatively small proportion of patients developing EndoCAb depletion may contribute to the limitations of therapies that aim to augment natural defenses against endotoxin or the proinflammatory cytokines.     

Insulin resistance and hypertension in non-obese Africans in Tanzania

OBJECTIVE: This study was done to evaluate the differences in base deficit (BD) clearance, pH normalization, and the occurrence of complications between survivors and nonsurvivors after trauma. DESIGN: Concurrent data entry with retrospective review. METHODS: Trauma patients meeting registry criteria from July 1990 through August 1995 with arterial blood gases performed within 1 hour of admission and admission BD < or = -6 were included. Data was grouped by BD category (moderate, -6 to -9; severe, < or = -10). Group means +/- SEM were compared with a two-tailed t test. MEASUREMENTS and MAIN RESULTS: Six hundred seventy-four patients met entry criteria. Survivors in both the moderate and severe BD groups had improved their BD within 4 hours and normalized their BD by 16 hours. Nonsurvivors did not improve their BD category until 8 hours (for the severe group) and 16 hours (for the moderate group) and did not normalize BD before 24 hours. The BD differences between survivors and nonsurvivors were significant at each time interval, whereas pH differences were significant at 2 hours in the moderate group and at 2, 16, and 24 hours in the severe group. Patients who failed to improve their BD > -6 had an increased frequency of adult respiratory distress syndrome, multiple organ failure, and mortality. CONCLUSION: Base deficit reveals differences in metabolic acidosis between survivors and nonsurvivors not shown by pH determinations and is clearly a better marker of acidosis clearance after shock.     

APACHE III, unlike APACHE II, predicts posthepatectomy mortality in patients with biliary tract carcinoma. Acute Physiology and Chronic Health Evaluation

OBJECTIVE: To evaluate Acute Physiology and Chronic Health Evaluation (APACHE) II and APACHE III scores after liver resection and to elucidate whether APACHE III is more accurate as a predictor of posthepatectomy mortality. DESIGN: Retrospective, cohort study. SETTING: Intensive care unit in a tertiary care university hospital. PATIENTS: Consecutive series of 101 patients admitted to the intensive care unit immediately after elective hepatectomy for biliary tract carcinoma. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: APACHE II and APACHE III scores were calculated on postoperative days 1, 2, and 3. The 101 subjects were classified into three groups: a) survivors without posthepatectomy liver failure (n = 69); b) survivors with liver failure (n = 17); and c) nonsurvivors with liver failure (n = 15). APACHE III, but not APACHE II, was significantly different between the three groups at all time points. An increased APACHE III score correlated with an increased risk of death, while death did not correlate with APACHE II score. CONCLUSION: In posthepatectomy patients with biliary tract carcinoma, APACHE III, unlike APACHE II, is sufficiently reliable for clinical use to stratify patients and predict mortality.     

Prognostic value of blood lactate, base deficit, and oxygen-derived variables in an LD50 model of penetrating trauma

OBJECTIVE: To determine whether blood lactate, base deficit, or oxygen-derived hemodynamic variables correlate with morbidity and mortality rates in a clinically-relevant LD50 model of penetrating trauma. DESIGN: Prospective, controlled study. SETTING: University research laboratory. SUBJECTS: Anesthetized, mechanically-ventilated mongrel pigs (30+/-2 kg, n = 29). INTERVENTIONS: A captive bolt gun delivered a penetrating injury to the thigh, followed immediately by a 40% to 60% hemorrhage. After 1 hr, shed blood and supplemental crystalloid were administered for resuscitation. MEASUREMENTS AND MAIN RESULTS: After penetrating injury, 50.7+/-0.3% hemorrhage (range 50% to 52.5%), and a 1-hr shock period, seven of 14 animals died, compared with six of six animals after 55% to 60% hemorrhage, and 0 of nine animals after < or =47.5% hemorrhage. Only two of 13 deaths occurred during fluid resuscitation. At the LD50 hemorrhage, peak lactate concentration and base deficit were 11.2+/-0.8 mM and 9.3+/-1.5 mmol/L, respectively, and minimum mixed venous oxygen saturation, systemic oxygen delivery, and systemic oxygen consumption were 33+/-5%, 380+/-83 mL/min/kg, and 177+/-35 mL/min/kg, respectively. For comparison, baseline preinjury values were 1.6+/-0.1 mM, -6.7+/-0.6 mmol/L, 71+/-3%, 2189+/-198 mL/min/kg, and 628+/-102 mL/min/kg, respectively. Of all the variables, only lactate was significantly related to blood loss before and after fluid resuscitation in the 16 survivors. However, r2 values were relatively low (.20 to .50), which indicates that only a small fraction of the hyperiactacidemia was directly related to tissue hypoperfusion. In the whole population of survivors and nonsurvivors, both lactate and base deficit (but none of the oxygen-derived variables) correlated with blood loss. CONCLUSIONS: Arterial lactate is a stronger index of blood loss after penetrating trauma than base deficit or oxygen-derived hemodynamic variables. The reliability of arterial lactate depends on several factors, such as the time after injury, the proportion of survivors and nonsurvivors in the study population, and on factors other than tissue hypoxia.