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J L Vincent

Publications and source records attributed to J L Vincent.

At least 109 records · Page 6Linked to original sources
PubMed1999

Heparin-coated circuits reduce myocardial injury in heart or heart-lung transplantation: a prospective, randomized study.

BACKGROUND: The effects of heparin-coated (HC) circuits have been primarily investigated in routine cardiac operations with limited duration of cardiopulmonary bypass (CPB) and ischemia. Their benefits have not been conclusively proven but could be more significant when CPB and ischemic times are longer, such as during heart transplantation (HTx) or heart-lung transplantation (HLTx). METHODS: In a 22-month period, 29 patients undergoing HTx and HLTx were randomly divided into two groups using HC (Duraflo II, n = 14, 10 HTx and 4 HLTx) or uncoated but identical circuits (NHC group, n = 15, 10 HTx and 5 HLTx). All patients received full systemic heparinization (3 mg/kg) during CPB. Plasma endotoxin, interleukin (IL)-6, IL-8, IL-10, IL-12, and cardiac troponin-I were measured before heparin administration, immediately after aortic cross-clamping, 5, 30, 60, 90, 120 minutes, and 12 and 24 hours after aortic declamping. The intensive care unit (ICU) staff and the laboratory technologists were blinded as to the use of HC circuits. RESULTS: No statistically significant differences between groups were found with respect to all baseline values, duration of CPB and aortic cross-clamping, graft ischemic time, doses of heparin, postoperative blood loss and transfusion, peak lactate and creatine kinase-MB isoenzyme values, duration of mechanical ventilation, or length of ICU stay. One patient in each group died during the hospital stay. Patients in the HC group needed more protamine sulfate after CPB. Although endotoxin levels were similar in the two groups, significantly lower IL-6, IL-8, and IL-10 levels were observed 1 hour after aortic declamping in the HC group. The release of cardiac troponin-I was also significantly reduced in the HC group 12 and 24 hours after reperfusion. CONCLUSIONS: The use of HC circuit limits both pro- and anti-inflammatory responses to CPB. It may also reduce myocardial injury after prolonged duration of CPB and ischemia.

Adolescent↗
PubMed1999

Pharmacokinetics of the nitric oxide synthase inhibitor L-NG-methylarginine hydrochloride in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVES: To characterize the pharmacokinetics of L-NG-methylarginine in patients with septic shock. METHODS: This was an international, uncontrolled, open-label study of L-NG-methylarginine (546C88) therapy given to 32 patients with septic shock. It was conducted in hospital-based intensive care units that admit general surgical and medical patients. Patient cohorts received an infusion of L-NG-methylarginine at fixed dose rates of 1, 2.5, 5, 10, and 20 mg/kg/h for up to 8 hours. The 5 dosing regimens were administered sequentially to separate groups of patients. RESULTS: Of the 32 patients studied, 23 received complete 8-hour infusions. In the other 9 patients, the infusion was terminated prematurely within the first 1/2 to 4 hours. Median clearance of L-NG-methylarginine averaged 485 mL/h/kg for the 1 and 2.5 mg/kg/h dosing cohorts combined but decreased to 283, 181, and 98 mL/h/kg for the 5, 10, and 20 mg/kg/h dosing cohorts, respectively. Median renal clearance was similar at 9 to 26 mL/h for the 1, 2.5, and 5 mg/kg/h dosing cohorts but increased to 156 and 284 mL/h for the 10 and 20 mg/kg/h dosing cohorts, respectively. Median steady-state volume of distribution was similar in all 5 dosing cohorts, averaging 0.66 to 0.82 L/kg. CONCLUSIONS: The 80% decrease in clearance from 485 to 98 mL/h/kg with the increase in dose suggests that a predominant metabolic pathway(s) of L-NG-methylarginine, accounting for at least 80% of clearance, is becoming progressively saturable in association with L-NG-methylarginine infusion rates > or = 5 mg/kg/h. Therefore the use of L-NG-methylarginine infusion rates > or = 5 mg/kg/h are typically expected to result in progressive inhibition of nitric oxide synthase activity. Consequently, patient hemodynamics should be monitored closely to avoid an excessive increase in vasomotor tone, which would be manifest by either an increase in mean arterial pressure or a decrease in cardiac output. The infusion rates of conventional vasopressor(s) (eg, norepinephrine [BAN, noradrenaline]) or L-NG-methylarginine or both may need to be reduced accordingly.

Adult↗
PubMed1999

Does steroid pretreatment increase endotoxin release during clinical cardiopulmonary bypass?

OBJECTIVE: The mechanism involved in the endotoxemia frequently recognized during cardiopulmonary bypass remains unclear. It has also been suggested that endotoxin levels were higher in steroid-pretreated patients undergoing cardiopulmonary bypass. METHODS: Twenty patients undergoing cardiopulmonary bypass were randomly pretreated with steroids (methylprednisolone, 30 mg/kg) or placebo. Blood samples for endotoxin measurement were drawn simultaneously from the superior and inferior venae cavae before heparin administration, 5 and 50 minutes after the onset of bypass, 5 minutes after aortic declamping, at the end of bypass, and 1, 2, and 20 hours after the end of cardiopulmonary bypass. RESULTS: The perioperative variables in the two groups were similar. Blood endotoxin levels were higher in the inferior vena cava than in the superior vena cava immediately after the onset of bypass. Endotoxin levels in inferior vena cava blood were significantly lower in steroid-pretreated patients than those in patients not receiving steroids. CONCLUSIONS: Endotoxin is released during cardiopulmonary bypass from the region drained by the inferior vena cava. Steroid pretreatment may actually reduce endotoxin release during bypass.

Aged↗
PubMed1999

Leukocyte glycolysis and lactate output in animal sepsis and ex vivo human blood.

Lactate is released in large quantity from sites of sepsis and inflammation. We asked whether the increased lactate production found in sepsis can be explained by the augmented glycolysis of inflammatory cells. The glycolytic metabolism of rat peritoneal leukocytes was measured following cecal ligation and perforation (CLP) or sham laparotomy. CLP augmented glucose uptake, the pentose phosphate pathway, and glucose oxidation. Lactate output increased from 1.03 +/- 0.05 to 1.20 +/- 0.05 fmol x cell(-1) x min(-1) (P < .001). Total lactate output of peritoneal lavage fluid increased from 7.94 +/- 2.59 to 28.12 +/- 5.60 nmol L x min(-1) (P < .005). The effect of lipopolysaccharide (LPS) on the lactate output of whole blood from 31 critically ill patients was measured. Leukocyte lactate production was calculated by multiple linear regression analysis. Following exposure to LPS, human leukocyte lactate output increased from 0.20 +/- 0.09 to 1.22 +/- 0.14 fmol x cell(-1) x min(-1) (P < .001). This rate of production is so high that it suggests that the lactate output of different tissue beds in sepsis may be affected by their different cell populations and state of activation. This study supports the hypothesis that lactate may be more a product of inflammation than a marker of tissue hypoxia in sepsis.

Animals↗
PubMed1999

IL-1ra administration does not improve cardiac function in patients with severe sepsis.

PURPOSE: The purpose of this study was to investigate the effects of interleukin-1 receptor antagonist (IL-1ra) on myocardial function in septic patients. MATERIALS AND METHODS: A subgroup of patients from a prospective, randomized, double-blind, placebo-controlled, multicenter trial was studied from 63 academic medical centers in the United States, Canada, and Europe. A subgroup of 71 patients with severe sepsis in whom vasoactive support was little altered during the study was included. The patients were randomized to receive either placebo (n = 29) or IL-1ra at a dose of 1 mg/kg/h (n = 20) or 2 mg/kg/h (n = 22). RESULTS: Hemodynamic measurements were taken at baseline, and 1, 2, 3, 4, 8, and 12 hours after placebo or IL-1ra administration. No significant differences in hemodynamic parameters were observed between the groups or over time during the study period. CONCLUSIONS: IL-1ra administration has no effect on cardiac function in septic patients.

Blood Gas Analysis↗
PubMed1999

Relationship between plasma levels of lipopolysaccharide (LPS) and LPS-binding protein in patients with severe sepsis and septic shock.

Plasma endotoxin and lipopolysaccharide-binding protein (LBP) levels were measured in a group of 253 patients at the onset of severe sepsis and/or septic shock. Endotoxin levels were significantly greater than control levels (n=33; mean +/- SD, 5.1+/-7.3 pg/mL) in 78.3% of patients. Median endotoxin levels in patients with sepsis were 300 pg/mL (25%-75% interquartile range, 110-726 pg/mL). LBP levels were elevated in 97% of patients compared with normal control values of 4.1+/-1.65 microgram/mL. Median LBP levels in patients with sepsis were 31.2 microgram/mL (interquartile range, 22.5-47.7 microgram/mL). Median endotoxin levels at study entry were more highly elevated (515 vs. 230 pg/mL; P<.01), and LBP levels were less highly elevated (28.0 vs. 33.2 microgram/mL; P<.05) in nonsurvivors than survivors over the 28-day study period. No correlation was found between endotoxin and LBP levels. The quantitative level of both endotoxin and LBP may have prognostic significance in patients with severe sepsis.

Acute-Phase Proteins↗
PubMed1999

The Brussels sedation scale: use of a simple clinical sedation scale can avoid excessive sedation in patients undergoing mechanical ventilation in the intensive care unit.

Sedation is an important component of patient comfort in the intensive care unit (ICU), especially in those undergoing mechanical ventilation. Sedation that is too light or too deep can have important consequences, and therefore assessment of the degree of sedation should be an important part of patient management. Although there are many methods available to assess the degree of sedation, none is ideal. Therefore, we developed a new sedation scale and analysed its clinical impact in the management of patients undergoing mechanical ventilation. The study comprised two consecutive phases. In the first phase, the medical team did not use a sedation scale. In the second phase, the medical staff used the new sedation scale, comprising five levels, depending on the perceived degree of sedation: levels 1 and 2 = oversedation; levels 3 and 4 = correct sedation; and level 5 = undersedation. There were no significant differences in mean or highest levels between patients in the two phases (mean 2.89 (SD 0.11) vs 2.67 (0.13), P = 0.22; highest 3.16 (0.11) vs 3.10 (0.14), P = 0.78). However, the lowest level was significantly greater in patients in the second phase than in those in the first phase (2.61 (0.11) vs 2.16 (0.13); P = 0.011), indicating that the number of patients with excessive sedation was significantly reduced with the introduction of this scale. Thus the use of this scale can have a real clinical impact for patients undergoing mechanical ventilation, principally by avoiding excessive sedation.

Procedural Sedation↗
PubMed1999

Procalcitonin used as a marker of infection in the intensive care unit.

OBJECTIVE: To determine the value of procalcitonin (ProCT) as a marker of infection in critically ill patients. DESIGN: Prospective, observational study. SETTING: Medicosurgical department of intensive care (31 beds). PATIENTS: One hundred eleven infected and 79 noninfected patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ProCT and C-reactive protein (CRP) concentrations were monitored daily. The best cutoff values for ProCT and CRP were 0.6 ng/mL and 7.9 mg/dL, respectively. Compared with CRP, ProCT had a lower sensitivity (67.6 vs. 71.8), specificity (61.3 vs. 66.6), and area under the receiver operating characteristic curve (0.66 vs. 0.78, p < .05). The combination of ProCT and CRP increased the specificity for infection to 82.3%. In the infected patients, plasma ProCT, but not CRP, values were higher in nonsurvivors than in survivors. Infected patients with bacteremia had higher ProCT concentrations than those without bacteremia, but similar CRP concentrations. ProCT levels were particularly high in septic shock patients. CONCLUSIONS: ProCT is not a better marker of infection than CRP in critically ill patients, but it can represent a useful adjunctive parameter to identify infection and is a useful marker of the severity of infection.

Adolescent↗
PubMed1999

An open-label dose escalation study of the nitric oxide synthase inhibitor, N(G)-methyl-L-arginine hydrochloride (546C88), in patients with septic shock. Glaxo Wellcome International Septic Shock Study Group.

OBJECTIVE: To assess the effects of the nitric oxide synthase inhibitor, 546C88, in patients with septic shock and to evaluate the range of dose rates that sustain mean arterial pressure (MAP) of > or =70 mmHg. DESIGN: Multicenter, open-label, uncontrolled, dose range finding study. SETTING: Ten intensive care units in Europe and the United States. PATIENTS: Thirty-two patients with septic shock diagnosed within <24 hrs. INTERVENTIONS: Patients received a fixed dose rate of 546C88 at either 1(n = 6), 2.5 (n = 6), 5 (n = 4), 10 (n = 5), or 20 mg/kg/hr (n = 11) by intravenous infusion for up to 8 hrs. Conventional vasoactive therapy was restricted to norepinephrine and/or dobutamine. During 546C88 therapy, MAP was to be maintained between 70 and 90 mm Hg, while attempting to withdraw any concurrent norepinephrine. MEASUREMENTS AND MAIN RESULTS: Systemic and pulmonary hemodynamics, blood gases, and plasma nitrate were assessed. Infusion of 546C88 (1-20 mg/kg/hr) for up to 8 hrs enabled a 60 to 80% reduction of the norepinephrine dose rate in all cohorts, while MAP was sustained at >70 mm Hg. There was an increase in vascular tone and a decrease in cardiac index within the 1st hr of therapy. Systemic vascular resistance returned toward baseline with reduction of concomitant administration of norepinephrine. The decline in oxygen delivery was associated with an increase in extraction and, therefore, the maintenance of oxygen consumption. There was a sustained reduction of venous admixture within the 1st hr of therapy. 546C88 was not associated with any major or dose-dependent adverse effect on pulmonary, hepatic, or renal function. CONCLUSIONS: Treatment with the nitric oxide synthase inhibitor, 546C88, can restore the balance of vasomotor tone, thereby, maintaining blood pressure and reducing or eliminating the requirement for norepinephrine therapy in patients with septic shock. Infusion of 546C88 (1-20 mg/kg/hr) appears to have a satisfactory overall safety profile.

Adult↗
PubMed1999

Forgoing life support in western European intensive care units: the results of an ethical questionnaire.

OBJECTIVE: To determine current views of European intensive care physicians regarding end-of-life decisions. DESIGN: A questionnaire was sent to all physician members of the European Society of Intensive Care Medicine. All questionnaires were anonymous. RESULTS: A total of 504 completed questionnaires from 16 western European countries were analyzed. Eighty-seven percent of the respondents were male. Forty-six percent of respondents said that intensive care unit admissions were generally or commonly affected by bed shortages, particularly in the south. Nevertheless, 73% of units frequently admit patients with no hope of survival, although only 33% of respondents felt that such patients should be admitted. Eighty percent of respondents felt that written do-not-resuscitate orders should be applied, but only 58% did so, with a wide variation according to country (from 8% in Italy to 91% in The Netherlands). Ninety-three percent of physicians sometimes withhold treatment from patients with no hope of a meaningful life, but withdrawal of treatment is less common. Forty percent of respondents said that they would deliberately administer large doses of drugs to such patients until death ensued. Forty-nine percent of respondents involved staff, patients, and family in end-of-life decisions. Forty-five percent of respondents felt that an ethics consultation was useful in such situations. Physicians in the countries of southern Europe were less likely than those in the north to apply do-not-resuscitate orders, withhold treatment, and discuss such issues with the patients. However, they were more likely to value the opinion of an ethics consultant. CONCLUSIONS: Intensive care unit admissions are frequently limited by the availability of beds across Europe, particularly in the south and in the United Kingdom, yet 73% of intensivists still admit patients with no hope of survival. When treating patients with no hope of survival, 40% of intensivists will deliberately administer large doses of drugs until death ensues. There are interesting differences between what a physician actually does and what he or she believes should be done with regard to various ethical questions. Important differences in attitudes also exist between European countries.

Adult↗
PubMed1999

Continuous venovenous hemofiltration improves cardiac performance by mechanisms other than tumor necrosis factor-alpha attenuation during endotoxic shock.

OBJECTIVE: To assess the effects of continuous venovenous hemofiltration (CWH) on global and regional hemodynamics, plasma lactate, and tumor necrosis factor-oa (TNF-a) levels during endotoxic shock in dogs. METHODS: Thirty pentobarbital-anesthetized and mechanically ventilated dogs were divided into six groups of five dogs each. Group 1 served as a control, undergoing CWH at 3 Uhr without endotoxin. Group 2 served as the endotoxin-alone time-matching group. Group 3 received CWH 1 hr after endotoxin at 3 Uhr for 270 mins. Group 4 received CWH 1 hr after endotoxin at 3 Uhr for 150 mins and at 6 Uhr for an additional 120 mins. Group 5 and group 6 received the ultrafiltrate from group 1 and group 3, respectively. MEASUREMENTS AND MAIN RESULTS: Three hours after endotoxin challenge, dogs treated with CWH at 3 Uhr had a higher cardiac output (4.9 + 0.6 vs. 2.9 + 0.6 Umin; p < .05) and stroke volume (35 + 7 vs. 20 + 4 mL; p < .05) and a lower pulmonary vascular resistance (116 26 vs. 331 + 126 dyne-sec/cm5; p < .05) than the endotoxin-alone group. Five hours after endotoxin, dogs treated with CWH at 6 Uhr also had higher hepatic (464 + 164 vs. 126 + 75 mUmin; p < .05) and femoral (95 + 46 vs. 30 + 34 mL/min; p < .05) blood flow. Moreover, dogs treated with CWH at 6 Uhr had higher mean arterial blood pressure (84 + 24 vs. 40 + 15 mm Hg; p < .05) and left ventricular stroke work index (1.1 + 0.6 vs. 0.2 + 0.2 g/kg; p < .05) than the endotoxin-alone group. Plasma lactate levels were lower in the CWH group at 6 Uhr (2.7 + 1.1 mmol/L) than in the endotoxin-alone group (4.4 + 0.6 mmol/L; p < .05). Plasma TNF-ao levels were unaffected, and only minor amounts of TNF-o were found in the ultrafiltrate. CONCLUSION: In this acute endotoxic shock model, CWH at 3 Uhr improved cardiac performance and decreased pulmonary vasoconstriction. Moreover, CWH at 6 LUhr also increased arterial blood pressure and left ventricular stroke work, increased hepatic and femoral arterial blood flow, and decreased blood lactate levels. These effects were not attributable to TNF-alpha removal.

Analysis of Variance↗
PubMed1999

Does gastric tonometry monitor splanchnic perfusion?

OBJECTIVE: To define whether the gastric mucosal-arterial PCO2 gradient (PCO2 gap) reliably reflects hepatosplanchnic oxygenation in septic patients. DESIGN: Prospective observational clinical study. SETTING: An adult, 31-bed medical/surgical department of intensive care of a university hospital. PATIENTS: A total of 36 hemodynamically stable, invasively monitored, mechanically ventilated, sedated, paralyzed patients with severe sepsis. INTERVENTIONS: In each patient, hepatosplanchnic blood flow was determined by the continuous indocyanine green infusion technique and gastric mucosal PCO2 by the saline tonometry technique. Suprahepatic venous blood oxygen saturation and PCO2 also were measured. The mesenteric veno-arterial PCO2 gradient was determined as the difference between the suprahepatic venous blood PCO2 and the arterial blood PCO2. MEASUREMENTS AND MAIN RESULTS: There were significant correlations between the hepatosplanchnic blood flow and the suprahepatic venous blood oxygen saturation (r2 = .56; p<.01), between the hepatosplanchnic blood flow and the mesenteric veno-arterial PCO2 gradient (r2 = .55; p<.01), and also between the suprahepatic venous blood oxygen saturation and the mesenteric veno-arterial PCO2 gradient (r2 = .64; p<.01). There was no statistically significant correlation between the PCO2 gap and the hepatosplanchnic blood flow, the suprahepatic venous blood oxygen saturation or the mesenteric veno-arterial PCO2 gradient. CONCLUSIONS: In stable septic patients, the PCO2 gap is not correlated with global indexes of gut oxygenation. The interpretation of PCO2 gap is more complex than previously thought.

Blood Flow Velocity↗
PubMed1999

Arterial baroreflex control of the sinus node during dobutamine exercise stress testing.

The contributions of increases in circulating catecholamines, changes in central command, and muscle afferents on baroreflex control of the sinus node during exercise are unclear. We used a dobutamine infusion to induce hemodynamic changes comparable to those of moderate physical exercise in the absence of changes in central command and muscle afferents in 13 healthy subjects. Dobutamine (up to 9 microg/kg body weight per minute) increased systolic blood pressure, shortened the RR interval, increased systolic blood pressure variability, but blunted RR interval variability (P<0.05 versus placebo). Consequently, dobutamine decreased the coherence between variations in systolic blood pressure and RR interval and decreased arterial baroreflex sensitivity from 12+/-2 to 3+/-1 ms/mm Hg (P<0.01). The largest increases in systolic blood pressure with dobutamine were paralleled by the greatest impairments in arterial baroreflex sensitivity (0. 50<r<0.56, P<0.01). The chronotropic effects of dobutamine prevented a reflex bradycardia in response to the blood pressure increase. However, less predominant low-frequency oscillations in systolic blood pressure (P<0.0001) suggested preserved sympathetic withdrawal in response to the blood pressure increase induced by dobutamine. In conclusion, this study revealed that a shift in the operating point of the arterial baroreceptors and the chronotropic effects of adrenergic stimulation impair baroreflex control of the sinus node during dobutamine exercise stress testing. Baroreflex control of the sinus node is not reset when hemodynamic characteristics of exercise are reproduced in the absence of modifications in central command and muscles afferents.

Adult↗
PubMed1999

A dobutamine test can disclose hepatosplanchnic hypoperfusion in septic patients.

In 36 hemodynamically stable septic patients, we explored whether changes in gastric mucosal-arterial PCO(2) gradient (PCO(2)gap) induced by a short-term dobutamine infusion may reveal hepatosplanchnic hypoperfusion. Hepatosplanchnic blood flow (HSBF) was determined by the continuous indocyanine green infusion technique and gastric mucosal PCO(2) (Pg(CO(2))) by saline tonometry. In each patient, hemodynamic measurements, blood samples, and Pg(CO(2)) determinations were performed three times: first at baseline (DOB 0), second during a dobutamine infusion at a dose of 5 microgram/kg/min (DOB 5), and third at a dose of 10 microgram/kg/min (DOB 10). The results were analyzed by Wilcoxon's matched-pairs signed rank test and are presented as medians with ranges. The PCO(2)gap decreased preferentially in groups of patients with inadequate hepatosplanchnic perfusion, i.e., with a low fractional HSBF (HSBF/CI), defined as the ratio of the HSBF to the simultaneous cardiac index, or a high gradient between the mixed venous blood and the suprahepatic blood O(2) saturations (DSvh(O(2))). In the 11 patients with a DSvh(O(2)) above 20% at baseline, PCO(2)gap decreased from 12.1 (6.3 to 19.5) mm Hg at DOB 0 to 6.2 (2.5 to 19. 3) mm Hg at DOB 5 (p < 0.001 versus DOB 0), and to 4.2 (0.1 to 35.9) mm Hg at DOB 10 (p < 0.05 versus DOB 5), whereas in the 25 patients with a DSvh(O(2)) below 20% at baseline, PCO(2)gap did not change significantly. At no time was the PCO(2)gap correlated with HSBF/CI or DSvh(O(2)). We conclude that although the PCO(2)gap does not correlate well with global indexes of gut oxygenation, such a simple dobutamine infusion test could identify patients with inadequate hepatosplanchnic perfusion.

Carbon Dioxide↗
PubMed1999

Management of the critically ill patient with severe sepsis.

Sepsis is a common cause of morbidity and mortality among the critically ill patient population. However, no anti-sepsis therapy has yet been found to be effective and treatment is thus largely supportive. Adequate fluid resuscitation must be accompanied by effective ventilation, and adrenergic agents may be needed to restore perfusion pressure and improve myocardial function. Enteral nutritional support with specialized nutrients has beneficial effects on morbidity, and should be started early. Further research will allow better definition of the septic patient according to immune status and enable more effective targeting of future anti-sepsis treatments.

Anti-Bacterial Agents↗