Peter M. Suter

Use of the Sofa score to assess the incidence of organ dysfunction/failure in intensive care units: Results of a multicenter, prospective study

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.

Candida colonization and subsequent infections in critically III surgical patients

ObjectiveThe authors determined the role of Candida colonization in the development of subsequent infection in critically ill patients.DesignA 6-month prospective cohort study was given to patients admitted to the surgical and neonatal intensive care units in a 1600-bed university medical center. MethodsPatients having predetermined criteria for significant Candida colonization revealed by routine microbiologic surveillance cultures at different body sites were eligible for the study. Risk factors for Candida infection were recorded. A Candida colonization index was determined daily as the ratio of the number of distinct body sites (dbs) colonized with identical strains over the total number of dbs tested; a mean of 5.3 dbs per patient was obtained. All isolates (n = 322) sequentially recovered were characterized by genotyping using contour-clamped homogeneous electrical field gel electrophoresis that allowed strain delineation among Candida species. ResultsTwenty-nine patients met the criteria for inclusion; all were at high risk for Candida infection; 11 patients (38%) developed severe infections (8 candidemia); the remaining 18 patients were heavily colonized, but never required intravenous antifungal therapy. Among the potential risk factors for candidal infection, three discriminated the colonized from the infected patients—i.e., length of previous antibiotic therapy (p < 0.02), severity of illness assessed by APACHE II score (p < 0.01), and the intensity of Candida spp colonization (p < 0.01). By logistic regression analysis, the latter two were the independent factors that predicted subsequent candidal infection. Candida colonization always preceded infection with genotypically identical Candida spp strain. The proposed colonization indexes reached threshold values a mean of 6 days before Candida infection and demonstrated high positive predictive values (66 to 100%). ConclusionsThe intensity of Candida colonization assessed by systematic screening helps predicting subsequent infections with identical strains in critically ill patients. Accurately identifying high-risk patients with Candida colonization offers opportunity for intervention strategies.

Acute renal failure in the ICU: risk factors and outcome evaluated by the SOFA score.

Objectives: To describe risk factors for the development of acute renal failure (ARF) in a population of intensive care unit (ICU) patients, and the association of ARF with multiple organ failure (MOF) and outcome using the sequential organ failure assessment (SOFA) score. Design: Prospective, multicenter, observational cohort analysis. Setting: Forty ICUs in 16 countries. Patients: All patients admitted to one of the participating ICUs in May 1995, except those who stayed in the ICU for less than 48 h after uncomplicated surgery, were included. After the exclusion of 38 patients with a history of chronic renal failure requiring renal replacement therapy, a total of 1411 patients were studied. Measurements and results: Of the patients, 348 (24.7 %) developed ARF, as diagnosed by a serum creatinine of 300 μmol/l (3.5 mg/dl) or more and/or a urine output of less than 500 ml/day. The most important risk factors for the development of ARF present on admission were acute circulatory or respiratory failure; age more than 65 years, presence of infection, past history of chronic heart failure (CHF), lymphoma or leukemia, or cirrhosis. ARF patients developed MOF earlier than non-ARF patients (median 24 vs 48 h after ICU admission, p < 0.05). ARF patients older than 65 years with a past history of CHF or with any organ failure on admission were most likely to develop MOF. ICU mortality was 3 times higher in ARF than in other patients (42.8 % vs 14.0 %, p < 0.01). Oliguric ARF was an independent risk factor for overall mortality as determined by a multivariate regression analysis (OR = 1.59 [CI 95 %: 1.23–2.06], p < 0.01). Infection increased the risk of death associated with all factors. Factors that increased the ICU mortality of ARF patients were a past history of hematologic malignancy, age more than 65 years, the number of failing organs on admission and the presence of acute cardiovascular failure. Conclusion: In ICU patients, the most important risk factors for ARF or mortality from ARF are often present on admission. During the ICU stay, other organ failures (especially cardiovascular) are important risk factors. Oliguric ARF was an independent risk factor for ICU mortality, and infection increased the contribution to mortality by other factors. The severity of circulatory shock was the most important factor influencing outcome in ARF patients.

Time course of platelet counts in critically ill patients.

Background Although thrombocytopenia in the intensive care unit (ICU) is associated with a poorer outcome, the precise relationship between the time course of platelet counts and the mortality rate has not been well defined. Objective To describe the time course of the platelet count in relation to the mortality rate in critically ill patients. Design Substudy of a prospective, multicenter, observational cohort analysis. Setting Forty ICUs in 16 countries from Europe, America, and Australia. Patients Data were collected from all ICU admissions in a 1-month period, excluding patients younger than 12 yrs old and those who stayed in the ICU for <48 hrs after uncomplicated surgery. A total of 1,449 critically ill patients were enrolled, including 257 who stayed in the ICU for >2 wks. Interventions None. Measurements Platelet counts were collected daily throughout the ICU stay, together with other measures of organ dysfunction. Thrombocytopenia was defined as a platelet count of <150 × 103/mm3. A relative increase in platelet count was defined as a 25% increase above the admission value, together with an absolute platelet count of ≥150 × 103/mm3. Main Results For the entire population, the platelet count was lower in the 313 nonsurvivors than in the 1,131 survivors throughout the ICU course. Of the 257 patients who stayed in the ICU for >2 wks, 187 (64%) survived. The platelet count decreased significantly in the first days after admission to reach a nadir on day 4 in both survivors and nonsurvivors. In the survivors, the platelet count returned to the admission value by the end of the first week and continued to rise to become significantly greater than the admission value by day 9. In the nonsurvivors, the platelet count also returned to the admission value after 1 wk, but there was no subsequent increase in platelet count. A total of 138 (54%) patients had thrombocytopenia on day 4, and these patients had a greater mortality rate than the other patients (33% vs. 16%;p < .05). On day 14, 51 (20%) patients had thrombocytopenia, and these patients had a greater mortality rate than the other patients (66% vs. 16%;p < .05). Thrombocytopenia was less common on day 14 than on day 4 (20% vs. 54%;p < .05), but the mortality rate was greater in the thrombocytopenic patients on day 14 than those who were thrombocytopenic on day 4 (66% vs. 33%;p < .05). The ICU mortality rate of nonthrombocytopenic patients on day 14 was also significantly lower in patients with, than without, a relative increase in platelet count on day 14 (11% vs. 30%;p < .05). Conclusion Platelet count changes in the critically ill have a biphasic pattern that is different in survivors and nonsurvivors. Late thrombocytopenia is more predictive of death than early thrombocytopenia. A relative increase in platelet count after thrombocytopenia was present in survivors but not in nonsurvivors. Although a single measured platelet count is of little value for predicting outcome, changes in platelet count over time are related to patient outcome.

Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis.

Plasma immunoreactive endothelin-1 concentrations were determined by radioimmunoassay in 11 septic patients during the first 24 hours after the development of the sepsis syndrome in 15 nonseptic postoperative patients studied 24 hours after open heart surgery and in 14 healthy volunteers. Mean endothelin-1 plasma concentrations were significantly (p less than 0.001) increased in septic patients (19.9 +/- 2.2 pg/mL, mean +/- standard error) compared to concentrations found in postoperative cardiac patients (11.9 +/- 0.7 pg/mL) or in healthy volunteers (6.1 +/- 0.3 pg/mL). In septic patients elevated plasma concentrations of endothelin-1 were inversely correlated with cardiac index (r = -0.80, p less than 0.005) and positively correlated the severity of illness as documented by APACHE II score (r = 0.74, p less than 0.01) and plasma creatinine levels (r = 0.80, p less than 0.005). No such correlations were found in postoperative cardiac patients. These results indicate that endothelin-1 concentrations are correlated with the severity of illness and depression of cardiac output in patients with sepsis.

The American-European Consensus Conference on ARDS, part 2. Ventilatory, pharmacologic, supportive therapy, study design strategies and issues related to recovery and remodeling.

The acute respiratory distress syndrome (ARDS) continues as a contributor to the morbidity and mortality of patients in intensive care units throughout the world, imparting tremendous human and financial costs. During the last ten years there has been a decline in ARDS mortality without a clear explanation. The American-European Consensus Committee on ARDS was formed to re-evaluate the standards for the ICU care of patients with acute lung injury (ALI), with regard to ventilatory strategies, the more promising pharmacologic agents, and the definition and quantification of pathological features of ALI that require resolution. It was felt that the definition of strategies for the clinical design and coordination of studies between centers and continents was becoming increasingly important to facilitate the study of various new therapies for ARDS.

Plasma concentrations of cytokines, their soluble receptors, and antioxidant vitamins can predict the development of multiple organ failure in patients at risk

OBJECTIVES The aims of this study were: a) to evaluate plasma concentrations of cytokines and their soluble receptors, as well as antioxidant substances in patients at high risk of developing multiple organ failure; b) to investigate early change: and c) to examine the possible prognostic value of these elements. DESIGN Prospective analysis. SETTING Surgical intensive care unit (ICU) of a university hospital. PATIENTS sixteen patients at risk for multiple organ failure. MEASUREMENTS AND MAIN RESULTS Ten patients developed multiple organ failure and five of them died. Whereas tumor necrosis factor-alpha (TNF-alpha) plasma concentrations were only borderline higher in patients developing multiple organ failure, TNF-soluble receptors 55 and 75 were significantly increased during all ICU days compared with patients not going into organ failure. Interleukin-6 plasma concentrations were higher in patients developing multiple organ failure during the first 2 days after ICU admission. The antioxidant vitamin C was significantly decreased in patients going into multiple organ failure during all ICU days. Other biochemical markers of antioxidant activity, such as vitamin E, copper, and zinc plasma concentrations, did not differ between the two groups. CONCLUSIONS Our data suggest that there is a marked increase in anti-TNF activity and a decrease of antioxidant defense in patients at risk of developing multiple organ failure. The predictive value of plasma concentrations of circulating TNF-soluble receptors and vitamin C in this type of patient needs further evaluation.

Respiratory Depression by Midazolam and Diazepam

The purpose of this study was to examine the respiratory depression produced by diazepam and by midazolam. Ventilatory and mouth occlusion pressure responses to CO2 were measured in eight healthy volunteers before and after the intravenous administration of 0.3 mg/kg of diazepam and 0.15 mg/kg of midazolam. The mean ventilatory response to CO2 ([OV0335] ± SEM) decreased after administration of diazepam or midazolam from 2.0 ± 0.2 to 1.3 ± 0.1 1 min−1/torr or from 2.1 ± 0.2 to 1.4 ± 0.1 1 min−1/torr, respectively. In the same volunteers, the mouth occlusion pressure responses decreased from 0.54 ± 0.05 to 0.30 ± 0.04 cm H2O/torr after midazolam and from 0.67 ± 0.12 to 0.28 ± 0.07 cm H2O/torr after diazepam. When compared with the control slopes of the ventilatory and mouth occlusion pressure responses, the drug slopes were significantly different. Respiration was similarly depressed after diazepam and after midazolam. That both the ventilatory and mouth occlusion pressure responses to CO2 are equally depressed by intravenous injections of midazolam and of diazepam at equipotent doses suggests a direct depression of the central respiratory drive by these drugs.

Review of medical prevention of vasospasm after aneurysmal subarachnoid hemorrhage: a problem of neurointensive care.

CEREBRAL VASOSPASM REMAINS a devastating medical complication of aneurysmal subarachnoid hemorrhage (SAH). It is associated with high morbidity and mortality rates, even after the aneurysm has been secured surgically or radiologically. A great deal of experimental and clinical research has been conducted in an effort to find ways to prevent this complication. The literature includes extensive coverage of in vivo animal model studies of SAH and vasospasm. These experimental studies have contributed to tremendous advances in the understanding of the mechanisms leading to cerebral vasospasm. Most of the experimental settings, however, have demonstrated varying levels of ability to predict accurately what occurs in human SAH. Therefore, although animal models have been developed to test new therapies, most of the treatment effects have been shown to be less compelling when trials have been conducted in clinical settings. The interpretation of current literature is complicated further by the imprecise estimation of the incidence of cerebral vasospasm, which is due to various degrees of clinical expression, ranging from the absence of symptoms in the presence of increased blood flow velocities at transcranial Doppler or vessel diameter reduction at angiography to neurological manifestations of severe ischemic deficits. In addition, a change over time in the incidence pattern of human SAH and vasospasm, possibly related to improved surgical techniques and overall patient management, may have occurred. This topic review collects the relevant literature on clinical trials investigating prophylactic therapies for cerebral vasospasm in patients with aneurysmal SAH and emphasizes the need for large clinical trials to confirm the results derived from clinical experience. In addition, it points out some experimental therapies that may hold promise in future clinical trials to prevent the occurrence of vasospasm.

Predicting outcome in ICU patients

ConclusionsConsiderable time and energy has been invested in the conception, modelling and evaluation of sophisticated severity scoring systems for ICU patients. These systems are created to enhance the precise estimation of hospital mortality for large ICU patient populations. Their current low sensitivity precludes their use for predicting out-come for individual ICU patients. However, severity scores can already be valuable for predicting mortality in groups of general ICU patients, and are very useful in the clinical trial setting.Outcome of ICU therapy, however, should incorporate more than mortality. Morbidity, disability and quality of life should also be taken into account; these factors were not taken into consideration in the design of the currently available severity scoring systems.At present, the severity scores have a very limited or no role in clinical decision-making for an individual patient, because they are based on a number of physiological and disease-oriented variables collected during the first 24 h after ICU admission. Future developments and subsequent validation of the dynamic process of clinical, physiological and organ-specific variables could improve the sensitivity and the value of severity scoring. Further collaborative developmental work in this field should be encouraged and supported across Europe and North America.