Biomedical subjects
Publications and source records attributed to D Journois.
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PURPOSE: It has been well recognized that the usefulness of the clinical examination and simple hemodynamic variables in the critically ill is limited. Modelization for hemodynamic analysis may improve the diagnostic performance by a systematic and multivariate analysis. This requires a rigorous formalization that may otherwise expand the usefulness of hemodynamic data, both as predictors and as therapeutic targets. Our study was designed to test the value of a model for assessing the pathophysiology of circulatory disorders and for establishing the diagnosis. METHODS: We tested all available variables using survival as the end point. A population of 223 patients (652 measurements) with compromised circulatory status was studied. We evaluated traditional variables: (1) morphological and physical data, (2) elementary right heart catheterization data, and (3) usually calculated variables, versus (4) new modeled variables. These new modeled variables were derived from a previously validated computer program for hemodynamic evaluation. They expressed differences between observed hemodynamic performance and estimated needs. RESULTS: Among traditional variables, major prognostic factors were: (1) in all patients, lactate level elevation, physical signs of hypoperfusion, and a decreased systemic arterial pressure; (2) in septic patients, a high PaO2/SaO2 ratio; (3) in nonseptic patients, low left ventricle work indices. In all cases, modeled hemodynamic variables assessing performance-needs adequacy enhanced the prognostic value of hemodynamic monitoring. CONCLUSIONS: Compared with traditional variables, modeled variables were found of greater interest to quantify pathophysiology of shock. These results enabled us to validate the initial step of the hemodynamic reasonning formalization and to develop "new" diagnostic criteria that more closely fit the interrelationship between pathophysiology, diagnosis, and prognosis.
Antithrombin-III (AT) is a key inhibitor of blood coagulation that neutralizes activated serine esterases by forming covalent modified complexes (ATm). A new monoclonal antibody directed against short-lived AT-activated serine protease complexes provides a means of measuring subclinical coagulation activity during cardiopulmonary bypass (CPB). Twelve patients undergoing CPB for coronary artery bypass grafting were studied and AT, ATm, D-dimers (DD), and several other coagulation and fibrinolytic markers were measured during the surgical procedure. There were decreases in AT, factors V, II, X, IX, protein S (total and free), C4b-binding protein, thrombomodulin, and platelets counts, whereas heparin, ACT, thrombospondin, plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) increased. ATm and the percentage of ATm available (ATm/AT) showed a peak during CPB. These results demonstrate that during CPB, the use of heparin produces an equilibrium involving increased coagulation activation and consumption in association with increased fibrinolysis. The equilibrated consumption of both coagulation and fibrinolytic factors leads to low levels of all factors after cardiac surgery. The ATm assay allows assessment of the differential effects of CPB and surgical trauma on coagulation activation. It is speculated that ATm levels may be useful in monitoring the consumption of coagulation factors.
BACKGROUND: This prospective study was intended to determine in a homogeneous population of children whether hemofiltration, performed during cardiopulmonary bypass rewarming, is able to improve hemodynamics and biologic hemostasis variables, to reduce postoperative blood loss, time to extubation, and plasma cytokines, and complement fragments. METHODS: Thirty-two children undergoing surgical correction of tetralogy of Fallot were randomly assigned to a hemofiltration or control group. Hemofiltration was performed with a polysulphone hemofilter during rewarming of cardiopulmonary bypass. Plasma clotting factors, D-dimers, antithrombin-III, complement fragments C3a and C5a, interleukin-1 beta, interleukin-6, interleukin-8, and tumor necrosis factor-alpha were measured before and after hemofiltration. Systemic mean arterial pressure, left atrial pressure, time to extubation, and postoperative blood loss were monitored. RESULTS: In the hemofiltration group, significant reductions in 24-h blood loss (250 (176-356) vs. 319 (182-500) ml/m2, median (minimum-maximum), time to extubation (15 (9-22) vs. 19 (11-24) h), plasma concentrations of C3a, C5a, interleukin-6, and tumor necrosis factor-alpha were observed compared to control. Arterial oxygen tension on admission to the intensive care unit was significantly greater in the hemofiltration group (136 +/- 20 vs. 103 +/- 25 mmHg, mean +/- SD). Significant increases in mean arterial pressure, clotting factors, and antithrombin-III were noted for the hemofiltration group. No intergroup difference was observed in left atrial pressure, platelets count, D-dimers, interleukin-8, and duration of stay in the intensive care unit. CONCLUSIONS: Hemofiltration during cardiopulmonary bypass in children improves hemodynamics and early postoperative oxygenation and reduces postoperative blood loss and duration of mechanical ventilation. Hemofiltration is able to remove some major mediators of the inflammatory response.
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Seventeen infants were treated with inhaled nitric oxide for critical pulmonary artery hypertension after operations for congenital heart defects. In all 17 patients conventional medical therapy consisting of hyperventilation, deep sedation/analgesia, and correction of metabolic acidosis had failed. All children were monitored with a transthoracic pulmonary artery catheter inserted at operation. Pulmonary artery hypertension was defined as an acute rise in pulmonary pressure associated with a decrease in oxygen arterial or venous saturation. After failure of conventional medical therapy, 20 ppm of inhaled nitric oxide was administered to the patient. In all patients the pulmonary pressures decreased (mean pulmonary arterial pressure decreased by -34% +/- 21%) without significant change in systemic arterial pressure, whereas the oxygen arterial saturation and oxygen venous saturation increased by 9.7% +/- 12% and 37% +/- 28%, respectively. Fifteen children were discharged from the intensive care unit at 10 +/- 6 days (range 3 to 26 days) and two died. This study demonstrates that inhaled nitric oxide exerts a selective pulmonary vasodilation without decreasing systemic arterial pressure in children with congenital heart disease. The increased values of mixed venous oxygen saturation and urinary output suggest that this selective lowering of pulmonary vascular resistance improved the overall hemodynamics. The potential toxic effects of nitric oxide and nitrogen dioxide necessitate careful consideration of the risks and benefits of inhaled nitric oxide therapy.
Mixed venous oxygen saturation (SvO2), measured on pulmonary artery blood, is a convenient indicator of matching between O2 transport (TaO2) and O2 body consumption (VO2). The measurement technique is based on the haemoglobin reflection spectrophotometry principle using two or three wave lengths. The Fick principle points out that SvO2 depends on five parameters: SvO2 = SaO2 - (VO2/CI x Hb x PO) where SaO2, CI and PO respectively represent arterial O2 saturation, cardiac index and O2 affinity. SvO2 does not always reflect tissue O2 tension: when considering a given value of SvO2, PvO2 will depend upon the position of the oxyhaemoglobin dissociation curve. It is impossible to establish in the absolute a "normal" value of SvO2. However, in most clinical circumstances, an SvO2 ranging from 60 to 80% attests that O2 tissue delivery is appropriate. Under certain conditions a continuous monitoring of SvO2 allows to assess another index such as ventilation-perfusion index or the O2 tissue extraction index. Usually SvO2 variations are more informative than the absolute SvO2 value. However, their interpretation should be cautious. First and foremost, the ability of each of the four main SvO2 determinants to influence the SvO2 is unequal as the numerical ranges of variation of these determinants are very different. Moreover, the attribution of a variation of SvO2 to one of its determinants implies that each of them is independent from the others, a feature which is very rarely seen in clinical practice. Finally as the mathematical relationship between SvO2 and its determinants is linear (SaO2 and VO2), or hyperbolic (CI and Hb), the weight of SaO2 or VO2 is independent of their absolute value, whereas CI or Hb weights will depend on their value. The limits of SvO2 monitoring are linked first to the occurrence of an anaerobic metabolism state when TaO2 becomes too low; SvO2 then just provides informations on the aerobic part of the metabolism. Moreover, SvO2 is just a global indicator for tissue O2 oxygenation status which does not give any indication about regional flow distribution. Therefore, SvO2 enables systemic imbalance supervision only. Finally, the existence of a right-to-left shunt will modify the SvO2 values through various mechanisms. However the SvO2 measured, in the pulmonary artery, remains reliable, whereas the presence of a left-to-right shunt will highly alter SvO2 basal value, only its time course remaining significant. SvO2 monitoring, element of diagnosis and monitoring, as well as a warning signal, has a priori specific indications poorly assessed, so far. (ABSTRACT TRUNCATED AT 400 WORDS)
Twenty-one patients (mean age 46 +/- 13 years) due to undergo abdominal or ENT surgery, presumed to give rise to an important blood loss were included in this study. None had any contra-indication to the use of normovolaemic haemodilution (NH). Mean initial haematocrit was 40.3 +/- 1.8%. Their estimated total blood volume was 4,867 +/- 857 ml. The patients were anaesthetized with thiopentone, fentanyl, vecuronium or atracurium. Maintenance was carried out with isoflurane (0.5% during NH). Usual haemodynamic monitoring was used throughout. The required haematocrit was decided on before starting NH. The amount of blood to be removed was calculated with usual mathematical formulae. A radial artery cannula (n = 7), or a subclavian or femoral venous cannula (n = 14) was used to remove blood, which was collected within a bag containing CPC-adenine. Six % hydroxyethyl starch (Elohes) was given through a short venous cannula some distance from the first one. An antiparallel double line set in a roller pump was used to carry out the NH. A mean 1,341 +/- 405 ml of blood were withdrawn so as to reach a mean haematocrit of 30.6 +/- 2.4%. NH was completed within 17 +/- 6 min. No major haemodynamic changes occurred during the procedure. No significant differences were observed between expected and observed final haematocrits. There was no effect of the volume of blood withdrawn on the error of haematocrit prediction (0.5 +/- 0.3%). However, a higher rate of blood removal could increase this error. This easy-to-use device seems to provide fast and identical rates of blood removal and replacement. The expected haematocrit may thus be reached reliably, even if this must be checked for the sake of safety.
OBJECTIVES: a) To evaluate the frequency, types, severity, and morbidity of iatrogenic complications; b) determine associated factors that favor iatrogenic complications; and c) suggest new or more efficient protective measures that may be taken to improve patient safety. DESIGN: Prospective, observational study. SETTING: Two ICUs in France. PATIENTS AND METHODS: The study included 382 patients (age > or = 15 yrs; 400 consecutive admissions). Patients were monitored by two physicians in each ICU to assess all iatrogenic complications occurring during their ICU stay, with the exception of adverse effects of drugs. An iatrogenic complication was defined as an adverse event that was independent of the patient's underlying disease. RESULTS: We observed 316 iatrogenic complications in 124 (31%) of the 400 admissions. Of these iatrogenic complications, 107 (in 53 [13%] of the 400 admissions) complications were major, three leading to death. Severe hypotension, respiratory distress, pneumothorax, and cardiac arrest represented 78% of the major iatrogenic complications. Fifty-nine percent of the major iatrogenic complications had clearly identified associated factors. Human errors accounted for 67% of these factors. Patients > 65 yrs (adjusted odds ratio = 2.6, 95% confidence interval: 1.4 to 4.9) and those patients admitted with two or more organ failures (adjusted odds ratio = 4.8, 95% confidence interval: 2.5 to 9.2) were more likely to develop major iatrogenic complications. High or excessive nursing workload also led to an increased risk of major iatrogenic complications. Persistent morbidity, secondary to iatrogenic complications at the time of discharge, was present in five survivors. The risk of ICU death was about two-fold higher for the patients with major iatrogenic complications than in the remaining patients after adjusting for the Organ System Failure Score and the prognosis of the disease (relative risk = 1.92, 95% confidence interval: 1.28 to 2.56). CONCLUSIONS: Major iatrogenic complications were frequent, associated with increased morbidity and mortality rates, related to high or excessive nursing workload, and were often secondary to human errors. To improve patient safety in our ICUs, preventive measures should be targeted primarily on the elderly and the most severely ill patients. Special attention should be given to improving the organization of workload and training, and promoting wider use of noninvasive monitoring.
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Continuous haemofiltration (CHF) mimics physiological glomerular filtration. Blood flows through a haemofilter, which is permeable to water and to all those substances not bound to plasma proteins, of up to about 6,000 d molecular weight. Ten to twenty liters of ultrafiltrate (UF) can be filtered daily. Solute concentration in this UF is very similar to that in plasma water. Because of the large volumes involved, the UF must be replaced continuously with an electrolyte solution. Electrolyte and acid-base disturbances can thus be easily and rapidly corrected. There are different techniques of CHF. Continuous arteriovenous haemofiltration (CAVH) avoids the use of an external blood pump, as the patient's own arterial pressure is used to drive the blood through the filter via a large-bore arterial catheter. On the other hand, continuous venovenous haemofiltration (CVVH) requires the use of a blood pump with a pressure alarm and an air bubble detector. Supplementary diffusive transport [CAVH(D),CVVH(D)] can improve the clearance of low molecular weight toxins, such as urea. In these techniques, there is a continuous flow of dialysate in the UF compartment of the haemofilter. One of the major problems with CHF is the anticoagulation of patients who are at risk of developing haemorrhagic complications. Unfractionated heparin is used most often, but other drugs have been used: low molecular weight heparin, prostacyclin, nafamostat, or sodium citrate. The neutralization of heparin has also been suggested. Because the fluid balance can be easily managed by CHF, patients in acute renal failure can be given standard intravenous feeding. Many small endogenous molecules, such as gastrin, are probably removed by CHF. However, most drugs have a molecular weight less than 6,000 d, and are not totally protein-bound. They are therefore likely to be ultrafiltered, and so, become inefficient. As a result, the drugs used should be adapted to the haemofilter, and vice versa. More than any extracorporeal circulation, CHF increases the incidence of bacterial blood contamination, because of its continuous use. Routine blood cultures should be carried out. Moreover, blood is cooled during its passage in the extracorporeal circuit, leading to hypothermia. There are some devices which prevent this. Renal function can be completely replaced with the production of 12 to 15 l UF a day. CHF must be started early on in the course of the renal failure. When the concentration of blood urea is greater than 40 mmol.l-1 diffuse transport must also be used.(ABSTRACT TRUNCATED AT 400 WORDS)
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Three modes of administration of alfentanil were assessed in order to reduce pain on injection with propofol. Forty healthy children scheduled for ENT surgery were included in this double-blind randomized study. All patients received intrarectal premedication with midazolam and atropine. Pain was scored with a behavioral scale. The children experience pain when alfentanil was administered a few seconds before or just after propofol. An bolus injection reduced significantly discomfort in patients. Dosages of alfentanil in plasma might determine the right moment of propofol injection to obtain analgesia.
The study objective was to describe the clinical, biologic, and hemodynamic features of adult overwhelming meningococcal purpura and to examine the prognostic factors by multivariate analysis at the time of admission to the intensive care unit. Thirty-five patients (greater than or equal to 13 years of age) with meningococcal infection, circulatory shock, and generalized purpuric lesions of abrupt onset were recorded in eight intensive care units from 1977 to 1989. The patients were young (mean age, 26.6 years; range, 13 to 68 years) and had been previously healthy. The female-to-male ratio was 3:1. Mortality was 54.3%, with most deaths occurring within the first 48 hours, usually secondary to irreversible shock with multiple organ failure. Ischemic complications (eight cases), prolonged heart failure (seven cases), and secondary septicemia (five cases) were the chief complications among survivors. Initial hemodynamic study after volume loading showed low stroke volume index (mean +/- SD, 29.4 +/- 13 mL/m2) and tachycardia (mean +/- SD, 138 +/- 16 beats per minute), a profile suggesting a greater myocardial depression than usually observed in gram-negative bacillary septic shock. Univariate prognostic analysis showed that four variables at the time of admission were associated with fatal outcome: a plasma fibrinogen level of 1.5 g/L or less, a factor V concentration of 0.20 or less, a platelet count lower than 80 x 10(9)/L, and a cerebrospinal fluid leukocyte count of 20 x 10(6)/L or less. Stepwise regression analysis showed that low fibrinogen level (less than or equal to 1.5 g/L) was the sole adverse prognostic variable (odds ratio = 2, 95% confidence interval, 1.5 to 2.7). Adult overwhelming meningococcal purpura is still associated with high mortality and morbidity. Low fibrinogen level at time of admission may permit early recognition of the most severely ill patients.
Continuous venovenous hemofiltration with dialysis (CVVHD) is being increasingly used to treat acute renal failure. However, because of the-lack of data on the clearance of therapeutic agents during this treatment, there is a risk of using inappropriate dosages. This in vitro study was undertaken to determine the clearance of pefloxacin (P) and its two main metabolites (active N-desmethyl P and inactive N-oxide P) during CVVHD. Acitrate-dextrose (ACD) anticoagulated fresh human blood containing P and its two metabolites in the usual therapeutic levels was circulated at a rate of 100 ml min.-1 through a closed-circuit continuous venovenous hemofiltration with dialysis unit (BSM 22-Hospal hemofilter). Temperature and ionic composition of the blood were controlled. Dialysate (L2D, Hospal) was circulated on the other side of the continuous venovenous hemofiltration with dialysis membrane at three different flow rates (Qdi) (0, 500 and 1,000 ml.h-1. The dialysate/ultrafiltrate outflow was adjusted using a withdrawal pump to obtain nul ultrafiltration. Arterial blood, venous blood and ultrafiltrate were sampled simultaneously at different time points for High Performance Liquid Chromatography (HPLC) assays and determination of the clearances (Cl) and sieving coefficients (s) of each compound. Pefloxacin had a sieving coefficient of 0.42 and a clearance of 6.8 ml min-1 when Qdi was nul. With the blood flow used, clearances were found to be correlated with the dialysate flow rate; when this rate was 500 ml h-1, a pefloxacin clearance similar to that seen in healthy subjects was obtained (15.2 ml min-1). The two bacteriologically active forms of the drug (pefloxacin and N-desmethyl P) had similar elimination parameters.(ABSTRACT TRUNCATED AT 250 WORDS)