Francis Cantraine

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.

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.

The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study

Objective: To evaluate the performance of total maximum sequential organ failure assessment (SOFA) score and a derived measure, delta SOFA (total maximum SOFA score minus admission total SOFA) as a descriptor of multiple organ dysfunction/failure in intensive care. Design: Prospective, multicentre and multinational study. Setting: Forty intensive care units (ICUs) from Australia, Europe, North and South America. Patients: Data on 1,449 patients, evaluated at admission and then consecutively every 24 h until ICU discharge (11,417 records) during May 1995. Excluded from data collection were all patients with a length of stay in the ICU less than 2 days following uncomplicated scheduled surgery. Main outcome measure: Survival status at ICU discharge. Interventions: The collection of raw data necessary for the computation of a SOFA score on admission and then every 24 h, and basic demographic and clinical statistics. Measurements and main results: Mean total maximum SOFA score presented a very good correlation to ICU outcome, with mortality rates ranging from 3.2 % in patients without organ failure to 91.3 % in patients with failure of all the six organs analysed. A maximum score was reached 1.1 ± 0.2 days after admission for all the organ systems analysed. The total maximum SOFA score presented an area under the ROC curve of 0.847 (SE 0.012), which was significantly higher than any of its individual components. The cardiovascular score (odds ratio 1.68) was associated with the highest relative contribution to outcome. No independent contribution could be demonstrated for the hepatic score. No significant interactions were found. Principal components analysis demonstrated the existence of a two-factor structure that became clearer when analysis was limited to the presence or absence of organ failure (SOFA score ≥ 3 points) during the ICU stay. The first factor comprises respiratory, cardiovascular and neurological systems and the second coagulation, hepatic and renal systems. Delta SOFA also presented a good correlation to outcome. The area under the receiver operating characteristic (ROC) curve was 0.742 (SE 0.017) for delta SOFA, lower than the total maximum SOFA score or admission total SOFA score. The impact of delta SOFA on prognosis remained significant after correction for admission total SOFA. Conclusions: The results show that total maximum SOFA score and delta SOFA can be used to quantify the degree of dysfunction/failure already present on ICU admission, the degree of dysfunction/failure that appears during the ICU stay and the cumulative insult suffered by the patient. These properties make it a good instrument to be used in the evaluation of organ dysfunction/failure.

Six-year results of a multimodality treatment strategy for locally advanced breast cancer

Between 1976 and 1982, 59 patients with locally advanced breast cancer were treated with preoperative supervoltage radiotherapy, adjuvant preoperative and postoperative hormonochemotherapy, and modified radical mastectomy. Systemic treatment, which was started simultaneously with radiotherapy, consisted of a combination of daily oral tamoxifen and a monthly alternation of Doxorubicin + vincristine and cyclophosphamide + methotrexate + 5‐fluorouracil (CMF). One of each cycle was given preoperatively at half dosage and five of each were repeated postoperatively at full dosage. All patients became operable. Results of pathologic examination of the operative specimen, available in 51 patients, showed complete disappearance of tumor tissue in breast areas in eight patients, of which three still had positive axillary nodes. After a median follow‐up time of 6 years locoregional failure was observed in 12 patients (20%) but in only three (5%) did it occur before distant failure. The actuarial median survival of the entire patient population is close to 4 years. Seven patients are alive without recurrence at >9 years. This aggressive multidisciplinary treatment approach is associated with a projected 30% long‐term survival (10 years), excellent local control, but substantial toxicity.

The diagnosis of fetal microcephaly

Of 16 fetuses in whom microcephaly was suspected, nine (56.2%) were affected with microcephaly, and seven (43.8%) were unaffected. Subsequently, nomograms with mean and SDs for biparietal diameter, occipitofrontal diameter, head perimeter: bdominal perimeter, biparietal diameter:femur length, and femur length:head perimeter we derived. With the use of the data from 27 sonograms of the 16 fetuses, different thresholds of abnormality were tested. Three standard deviations from the mean for biparietal diameter, occipitofrontal diameter, head perimeter, and femur length:head perimeter were sensitive thresholds for the diagnosis of fetal microcephaly with no false negative diagnoses. Four standard deviations from the mean for occipitofrontal diameter, head perimeter:abdominal perimeter, and femur length:head perimeter were specific tests with no false positive diagnoses. The use of multiple diagnostic tests was necessary to improve accuracy in the diagnosis of fetal microcephaly. Further clinical studies are needed to delineate more clearly optimal tests and thresholds of abnormality.

The First Object Oriented Monitor for Intravenous Anesthesia

Objective.To describe the design and implementation of“INFUSION TOOLBOX,” a software tool to control and monitormultiple intravenous drug infusions simultaneously using pharmacokinetic andpharmacodynamic principles. Methods.INFUSION TOOLBOX has been designedto present a graphical interface. Object Oriented design was used and thesoftware was implemented using Smalltalk, to run on a PC. Basic tools areavailable to manage patient, drugs, pumps and reports. These tools are thePatientPanel, the DrugPanel, the PumpPaneland theHistoryPanel. The screen is built dynamically. The panels may becollapsed or closed to avoid a crowded display. We also built control panelssuch as the Target ControlPanelwhich calculates the best infusionsequence to bring the drug concentration in the plasma compartment to a presetvalue. Before drug delivery, the user enters the patient’s data, selectsa drug, enters its dilution factor and chooses a pharmacokinetic model. Thecalculated plasma concentration is continually displayed and updated. Theanesthetist may ask for the history of the delivery to obtain a graphic reportor to add events to the logbook. A panel targeting the effect is used when apharmacodynamic model is known. Data files for drugs, pumps and surgery areupgradable. Discussion.By creating a resizeable ControlPanelwe enable the anesthetist to display the information he wishes, when hewishes it. The available panels are diverse enough to meet the anesthetistneeds; they may be adapted to the drug used, pumps used and surgery. It is theanesthetist who builds dynamically its different control screens.Conclusion.By adopting an evolutionary solution model we have achievedconsiderable success in building our drug delivery monitor. In addition wehave gained valuable insight into the anesthesia information domain that willallow us to further enhance and expand the system.

Administration of propofol by target-controlled infusion in patients undergoing coronary artery surgery

OBJECTIVES To study the predictive performance of a target-controlled infusion (TCI) system of propofol in patients undergoing coronary bypass graft (CABG) surgery, using a referenced pharmacokinetic set derived from healthy patients. Also, to determine the propofol concentrations required for clinically acceptable induction and maintenance of anesthesia when combined with midazolam as premedication and a continuous alfentanil infusion and to study the hemodynamic stability of this technique. DESIGN Prospective noncomparative study analysis. SETTING Operating room at a university hospital. PARTICIPANTS Twenty-on patients with good left ventricular function undergoing coronary artery surgery. INTERVENTIONS Patients were anesthetized using a continuous infusion of alfentanil (mean infusion rate: 1 microgram/kg/min) and propofol administered by TCI. MEASUREMENTS AND MAIN RESULTS The predictive performance of the TCI system (212 arterial samples) was measured at specified time points before, during, and after bypass. The TCI system underestimated the measured blood propofol concentrations with a bias of +21.2% and +9.6% during the prebypass and the bypass periods, respectively. The predictive inaccuracy, expressed by the median absolute prediction error, was 23% and 18.5%, respectively. Mean target propofol concentrations required to induce and maintain anesthesia before bypass were 0.92 microgram/mL and 3.64 micrograms/mL, respectively. In the period during and after bypass, the mean target concentrations required to maintain anesthesia was 2.22 micrograms/mL. The administration of propofol by TCI was still associated with some short episodes of hemodynamic instability that were easily controlled by adjusting the target concentration in the majority of the patients. Therefore, the overall quality and ease of control of anesthesia were considered as being good or adequate. CONCLUSIONS In this group of patients undergoing CABG surgery, the TCI system used underestimated the measured propofol concentrations. However, the predictive performance of the selected mean pharmacokinetic parameters derived from healthy patients was acceptable during the whole surgical procedure.

Translational control of protein synthesis: a simulation study.

Abstract A model for the translation phenomenon is developed which allows computer simulations of control of protein synthesis at the translational level. The main parameters governing the model are: the rate of initiation, the rate of progression of the ribosomes along the mRNA, the rate of release of ribosomes from the mRNA, the amount of ribosomal subunits and the amount of mRNA in the system. Simulations are performed which evidence the influence of these parameters on experimentally available data such as: polyribosome profiles, rate of protein synthesis, mean transit time of ribosomes and distribution of ribosomes along the mRNA. The aim of this work is to lead to easier interpretation of experimental works dealing with translational control of protein synthesis.

Placebo controlled pneumococcal immunization in patients with bronchogenic carcinoma

Pneumococcal vaccine [heptadecavalent types 1, 2, 3, 4, 6A, 7F, 8, 9N, 11A, 12F, 14, 15F, 17F, 18C, 19F, 23F and 25 pneumococcal capsular polysaccharide vaccine (Moniarix)] or placebo were evaluated in 26 and 21 patients with bronchogenic carcinoma, most of whom did not receive prior radiotherapy or chemotherapy. No difference was detected as far as clinical outcome is concerned: 3 vaccinated patients out of 26 (11.5%) developed pneumococcal infections (1 fatal bacteremia) and 4/21 (19%) of those who received a placebo presented such an infection (1 fatal bacteremia). The antibody response was significantly increased in the vaccines for types 1, 2, 7F, 8, 9N, 12F, 14, 17F, 18C, 23F and 25.

Administration of enoximone in cardiogenic shock

Thirteen patients in severe cardiogenic shock, persisting despite the use of adrenergic agents, were treated with enoximone, a recently available phosphodiesterase inhibitor. Cardiogenic shock was characterized by low cardiac output (less than 2.5 liter.min-1.m-2), elevated pulmonary artery balloon-occluded pressure (greater than or equal to 15 mm Hg), decreased urine output (less than 20 ml.hour-1) and increased blood lactate (greater than or equal to 2.0 mEq.liter-1). Ten patients were mechanically ventilated. A short-term intravenous infusion of 0.5 mg.kg-1 in 20 minutes of enoximone resulted in significant increases in cardiac index (from 1.8 +/- 0.3 to 2.9 +/- 0.3 liter.min-1.m-2, p less than 0.001) and stroke index (from 17.8 +/- 3.3 to 21.9 +/- 5.1 ml.m-2, p less than 0.001) and significant decrease in pulmonary artery balloon-occluded pressure (from 21.7 +/- 5.8 to 19.8 +/- 6.0 mm Hg, p less than 0.01) without a consistent change in mean arterial pressure (from 79 +/- 8 to 76 +/- 9 mm Hg, difference not significant). Enoximone administration decreased arterial oxygen tension (from 108 +/- 42 to 94 +/- 36 mm Hg, p less than 0.01) and increased venous admixture (from 12.8 +/- 6.5 to 16.0 +/- 8.0%, p less than 0.01). In 8 patients, a second infusion of 0.5 mg.kg-1 immediately thereafter amplified these changes. All patients but one survived the episode of cardiogenic shock and 5 patients left the hospital alive. These results indicate that the addition of enoximone to adrenergic agents in the treatment of cardiogenic shock can markedly increase cardiac output and stroke volume without substantial effects on arterial pressure.