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Biomedical subjects

J L Vincent

Publications and source records attributed to J L Vincent.

At least 91 records · Page 5Linked to original sources

Effects of nitric oxide in septic shock.

Nitric oxide (NO) is believed to play a key role in the pathogenesis of septic shock, although many aspects of NO's involvement remain poorly defined. Recent years have seen advances in our understanding of the production and effects of NO, but much of the work has been done in animal models and may not be directly relevant to the clinical situation. Differences between species and models can account for many of the apparently conflicting results obtained. Nevertheless, NO-directed strategies have been developed and tested clinically. However, NO can have both beneficial and detrimental effects on many organ systems in sepsis and attempts to nonselectively block all its actions may therefore not yield positive results on outcome. Further exploration and precision of the role of NO and development of techniques to assess the NO balance in individual patients is necessary before further progress can be made in this field.

Animals↗

Assessment of cardiac index in anemic patients.

STUDY OBJECTIVES: During isovolemic hemodilution, healthy individuals maintain oxygen consumption VO2 by identical increases in cardiac index (CI) and oxygen extraction ratio (O(2)ER). In critically ill patients, the relationship between CI and O(2)ER may be different. Patients with an altered cardiac function may have a decreased CI/O(2)ER ratio, whereas patients with sepsis may have an increased CI/O(2)ER ratio. We hypothesized that the analysis of the CI-O(2)ER relationship could help us to assess the adequacy of cardiac function in critically ill patients with anemia. DESIGN: Prospective, observational study. SETTING: Thirty-one-bed medicosurgical ICU of a university hospital. PATIENTS: Sixty patients equipped with arterial and Swan-Ganz catheters presenting with anemia, which was defined as a hemoglobin level < or = 10 g/dL in the absence of active bleeding. Patients were classified into those with compromised cardiac function (group 1; n = 40), and those with normal cardiac function (group 2; n = 20). MEASUREMENTS AND RESULTS: In addition to the pertinent clinical data, initial hemodynamic measurements, including pulmonary artery occlusion pressure (PAOP), CI, and O(2)ER, were collected in all patients at the onset of anemia. As anticipated, group 1 patients (n = 40) had lower CIs, higher O(2)ER levels, and lower CI/O(2)ER ratios than group 2 patients. However, there was no significant difference in PAOP values between the groups. The CI/O(2)ER ratio was < 10 in 27 of 40 group 1 patients but only in 4 of 20 group 2 patients. Of these latter four patients, three were found to be hypovolemic, and one patient with sepsis had severe myocardial depression. There was no statistically significant difference in PAOP in group 2 patients with or without hypovolemia ([mean +/- SD] 12.3+/-2.1 mm Hg) vs 13.7+/-4.3 mm Hg; p = 0.21). In group 1, survivors had a higher CI and CI/O(2)ER ratio than nonsurvivors. In group 2, however, such a relationship did not reach statistical significance. CONCLUSIONS: The relationship between CI and O(2)ER level can help interpret the CI in anemic patients. In anemic patients with no cardiac history, a low CI/O(2)ER ratio (< 10) suggests hypovolemia even when CI is not depressed.

Anemia, Hypochromic↗

Effects of a hydroxyethylstarch solution on plasma colloid osmotic pressure in acutely ill patients.

Hydroxyethyl starch (HES) solutions can represent an alternative to human albumin solutions in intensive care unit (ICU) patients, but their effects on the plasma colloid osmotic pressure (COP) have not been well defined. We studied the changes in COP in 61 critically ill patients; 39 patients received 500 ml HES 6% (Elo-Haes Fresenius solution) and 22 received 400 ml of a human albumin solution (4% albumin Belgian Red Cross) over 60 to 90 min. COP was determined with an oncometer, using a semi-permeable membrane at 30 Kd, before the infusion, at the end of the infusion, and one hour and four hours after the end of the infusion. COP increased in the HES group from 20.7 +/- 3.1 to 22.5 +/- 3.1 mmHg (p < 0.05), and this increase in COP was sustained throughout the 4 hours of the study. COP did not increase in the human albumin group (from 19.5 +/- 2.4 to 19.9 +/- 2.0 mmHg, NS). Hence, this standard HES solution has greater effects on COP than natural colloids. In view of their lower costs, HES solutions can represent a valuable alternative to human albumin. However, it is necessary to consider the secondary effects of HES and the physiologic functions of albumin.

Adult↗

Afelimomab.

Tumour necrosis factor-alpha (TNF-alpha) is well established as a key mediator in the inflammatory response seen in various disease processes including sepsis. TNF-alpha is involved in virtually all features of septic shock and multiple organ failure. Anti-TNF-alpha strategies are thus appealing and have been effective at reducing inflammation and morbidity in certain conditions including rheumatoid arthritis and Crohn's disease. Afelimomab is the F(ab')2 fragment of a murine anti-TNF-alpha antibody, and has been evaluated in clinical trials in septic patients. The results suggest that the drug is well tolerated, and may be of benefit in certain groups of patients with sepsis. A large, randomised, clinical trial of afelimomab in patients with severe sepsis has recently been completed and the results are eagerly awaited. More work is necessary to identify a means of selecting which patients are most likely to benefit from this type of therapy in sepsis.

Clinical Trials as Topic↗

[Ludwig's angina].

Ludwig's angina is a rare infectious condition originating in the oropharyngeal region, most commonly from the teeth. The principal symptoms consist of cervical pain, dyspnea, dysphagia, symmetrical neck swelling and fever. Serious complications include respiratory collapses, mediastinitis, pleural empyema, pericarditis and pericardial tamponade, and may result in the death of the patient. The most useful investigations in patients with suspected Ludwig's angina are clinical assessment, a cervico-thoracic CT-scan to determine the extent of the lesions, microbiological examination and panoramic radiography to detect possible dental focuses of infection. Treatment consists of ensuring adequate ventilation by securing the upper airways, broad spectrum antibiotic therapy, eradication of the source of infection, and often early surgical decompression may be necessary. Rapid diagnosis and appropriate treatment can reduce the mortality rate to 10%.

Adult↗

Clinically-oriented therapies in sepsis: a review.

Our insight of the sepsis response has evolved to encompass not only the pro-inflammatory but also an anti-inflammatory reaction following infection. Clinical trials have been designed to target either bacterial products, endotoxin in particular, or mediators involved in the sepsis response, but until recently the majority of them have given unfavorable results. In this article, we provide a scope of clinical trials that have been done in immunomodulation during sepsis whether or not they provide positive results. We will also discuss some of the reasons why those studies have been disappointing. Current and future trials with a better assessment of inflammatory status of patients and better-defined outcomes such as organ dysfunction are now underway.

Adjuvants, Immunologic↗

Hepato-splanchnic blood flow and oxygen extraction capabilities during experimental tamponade: effects of endotoxin.

We studied the hepato-splanchnic vascular response and changes in O2 extraction capabilities to a reduction in blood flow following endotoxemia. Fourteen anesthetized and mechanically ventilated dogs were divided into two groups of seven each. Group 1 received 2 mg/kg of E. coli endotoxin, and group 2 served as a control. After initial fluid resuscitation following endotoxic shock, regional blood flow estimated by an ultrasonic technique increased similarly in the hepatic artery, portal vein, and mesenteric artery, but microvascular blood flow estimated by a laser Doppler technique was lower in the liver than in the intestinal mucosa. When blood flow was reduced by cardiac tamponade, endotoxin-treated animals had greater whole body and regional critical O2 delivery (DO2crit) and lower whole body, liver, and intestinal critical O2 extraction ratios (O2ERcrit). DO2crit was higher in the liver than in intestine but O2ERcrit was similar in the two organs. Whole body DO2crit at the onset of organ O2 supply dependency was similar under control (9.4 +/- 1.9 mL/kg. min for whole body, 10.3 +/- 4.7 mL/kg. min for liver, and 10.0 +/- 2.6 mL/kg. min for intestine) and endotoxic conditions (13.6 +/- 3.2 mL/kg. min for whole body, 15.6 +/- 2.7 mL/kg. min for liver, and 15.4 +/- 8.7 mL/kg. min for intestine). We conclude that fluid-resuscitated endotoxic shock in dogs is characterized by blood flow redistribution within the liver and intestine. Microvascular depression may be more severe in the liver than in the intestinal mucosa, although the whole body, the liver, and the intestine became O2 supply-dependent simultaneously.

Animals↗

The 21-aminosteroid U74389G enhances hepatic blood flow and preserves sinusoidal endothelial cell function and structure in endotoxin-shocked dogs.

BACKGROUND: 21-Aminosteroids are potent anti-inflammatory and antioxidant drugs that provide remarkable endothelial protection in different models of tissue ischemia-reperfusion and inflammation. The effects of 21-aminosteroids in sepsis, a highly inflammatory condition leading to panendothelial activation and injury, are largely uninvestigated. We therefore explored the effects of the 21-aminosteroid U74386G on hepatic blood flow, endothelial cell function, and sinusoidal structure in a canine model of fluid-resuscitated, hyperdynamic endotoxic shock. MATERIALS AND METHODS: Following invasive hemodynamic monitoring and placement of ultrasonic flow probes around the common hepatic artery and the portal vein, 12 anesthetized dogs received 2 mg/kg iv of Escherichia coli endotoxin, followed by generous saline infusion, before randomization into two groups. One group (N = 6) received U74389G as an iv bolus of 80 microg/kg, followed by a continuous infusion of 10 microg/kg. min. The other group (N = 6) received an equivalent volume of vehicle. Hyaluronic acid was measured in plasma for in vivo evaluation of endothelial cell function. Liver biopsies were taken after 4 h of endotoxic shock and prepared for light and electron microscopic examination. RESULTS: Compared with the vehicle-treated controls, U74389G maintained a higher blood flow in the hepatic artery and in the portal vein, without markedly influencing the systemic hemodynamic response. The endotoxin-induced increase in plasma hyaluronic acid levels was significantly attenuated following U74389G treatment (70 +/- 14 vs 188 +/- 24 ng/mL after 3 h of endotoxic shock; P < 0.05). Morphological studies showed that the U74389G-treated group had less sinusoidal endothelial cell damage together with a dramatic reduction of neutrophil infiltration into the liver tissue. CONCLUSION: U74389G can preserve the functional and structural integrity of endothelial cells in the hepatic sinusoid during hyperdynamic endotoxic shock. This endothelial-protective effect was associated with a better maintained hepatic blood flow and a significant attenuation of inflammatory liver injury.

Animals↗

Nitric oxide production is enhanced in patients with heat stroke.

OBJECTIVE: To determine whether nitric oxide (NO) production is increased in heat stroke (HS) patients. DESIGN: A prospective analysis of nitrite and nitrate (NO2*/NO3) levels in ten HS patients was performed at the HS center in Makkah, Saudi Arabia. METHODS: Plasma (NO2*/NO3) levels were determined spectrophotometrically before cooling (0 time), and at 6, 12, and 24 h post-cooling. RESULTS: The mean level of NO in the ten HS victims before cooling was significantly higher than in eight control patients (35.6+/-37.0 vs. 3.0+/-4.2 micromol/l; p<0.01). The levels were higher in non-survivors than in survivors. NO also correlated positively with the Acute Physiology and Chronic Health Evaluation II score (r = 0.72, p<0.018). There was no correlation between the NO level before cooling and blood pressure, rectal temperature, or cooling time. CONCLUSION: HS is associated with excessive NO production, the magnitude of which is proportional to the severity of illness. NO may be an important mediator and integral part of the pathophysiological processes resulting in HS and may be a central factor linking the neurological and cardiovascular abnormalities observed in HS.

APACHE↗

Management of nutrition in European intensive care units: results of a questionnaire. Working Group on Metabolism and Nutrition of the European Society of Intensive Care Medicine.

OBJECTIVE: To describe the practical aspects of nutritional management in intensive care units (ICUs). DESIGN: A 49-item questionnaire was sent to the physician members of the European Society for Intensive Care Medicine. The issues addressed included: medical environment, assessment of nutritional status and current practice for enteral and parenteral nutrition. SETTING: 1608 questionnaires were sent in 35 European countries. ANALYSIS: The answers were pooled and stratified by country. RESULTS: 271 questionnaires were answered (response rate 17%). Assessment of nutritional status was generally based on clinical (99%) and biochemical (82%) parameters rather than on functional (24%), anthropometric (23%), immunological (18%) or questionnaire-based (11%) data. Two thirds of 2774 patients hospitalised in the corresponding ICUs at the time the questionnaire was answered were receiving nutritional support; 58% of those were fed by the enteral route, 23% by the parenteral route and 19% by combined enteral and parenteral. The preferred modality was enteral nutrition, instituted before the 48th h after admission, at a rate based on estimated caloric requirements. Specific and modified solutions were rarely used. Parenteral nutrition was less commonly used than enteral, although the practices differed between countries. It was mainly administered as hospital-made all-in-one solutions, at a rate based on calculated caloric requirements. CONCLUSIONS: European intensivists are concerned by the nutritional management of their patients. The use of nutritional support is common, essentially as early enteral feeding.

Critical Care↗

Application of SOFA score to trauma patients. Sequential Organ Failure Assessment.

OBJECTIVE: To assess the ability of the SOFA score (Sequential Organ Failure Assessment) to describe the evolution of organ dysfunction/failure in trauma patients over time in intensive care units (ICU). DESIGN: Retrospective analysis of a prospectively collected database. SETTING: 40 ICUs in 16 countries. PATIENTS: All trauma patients admitted to the ICU in May 1995. MAIN OUTCOME MEASURES AND RESULTS: Incidence of dysfunction/failure of different organs during the first 10 days of stay and the relation between the dysfunction, outcome, and length of stay. Included in the SOFA study were 181 trauma patients (140 males and 41 females). The non-survivors were significantly older than the survivors (51 years+/-20 vs 38+/-16 years, p < 0.05) and had a higher global SOFA score on admission (8+/-4 vs 4+/-3, p < 0.05) and throughout the 10-day stay. On admission, the non-survivors had higher scores for respiratory ( > 3 in 47% of non-survivors vs 17% of survivors), cardiovascular ( > 3 in 24% of non-survivors vs 5.7% of survivors), and neurological systems ( > 4 in 41% of non-survivors vs 16% of survivors); although the trend was maintained over the whole study period, the differences were greater during the first 4-5 days. After the first 4 days, only respiratory dysfunction was significantly related to outcome. A higher SOFA score, admission to the ICU from the same hospital, and the presence of infection on admission were the three major variables associated with a longer length of stay in the ICU (additive regression coefficients: 0.85 days for each SOFA point, 4.4 for admission from the same hospital, 7.26 for infection on admission). CONCLUSIONS: The SOFA score can reliably describe organ dysfunction/ failure in trauma patients. Regular and repeated scoring may be helpful for identifying categories of patients at major risk of prolonged ICU stay or death.

APACHE↗

Evaluation of a new, rapid lactate analyzer in critical care.

OBJECTIVE: To determine the reliability, precision and clinical usefulness of a newly developed substrate-specific lactate/blood gas analyzer (Chiron M865). SETTING: A university hospital 31-bed mixed medical/surgical intensive care unit (ICU). PATIENTS: Seventeen critically ill patients with sepsis (n = 4), post-cardiac surgery (n = 8), hepatic failure (n = 2) or acute respiratory failure (n = 3). MEASUREMENTS AND RESULTS: Lactate levels were measured in 17 critically ill patients on whole blood using the new Chiron M865, and on plasma by a stat lactate/glucose analyzer (Yellow Spring Instrument, YSI mode 2300) and a reference lactate/glucose/electrolyte/enzyme analyzer (Hitachi 911). The influences of temperature and storage on blood lactate levels were then evaluated. Mean lactate values obtained were 3.73+/-2.84 mmol/l with the Chiron, 3.03+/-2.60 mmol/l with the YSI, and 3.59+/-2.92 mmol/l with the Hitachi. There was a strong correlation between the three analyzers (Chiron vs YSI r = 0.99; Chiron vs Hitachi 911 r = 0.98), and good agreement between the Chiron and the two other methods (Chiron/YSI bias was -0.65, SD 0.50 mmol/l; Chiron/Hitachi bias was 0.12, SD 0.55 mmol/l). The variability coefficients were 3.7% for the Chiron and 3.0% for the YSI. During short term storage, a continuous increase in lactate levels was observed at room temperature (2.36+/-1.68 mmol/l to 2.53+/-1.74 mmol/l, p < 0.05), but when the samples were kept on ice there was just a small statistically significant, but not clinically significant, increase after 8 min (2.37+/-1.62 mmol/l to 2.39+/-1.63 mmol/l, p < 0.05). For longer storage times, samples on ice showed a small increase in lactate levels after 15 min (3.73+/-2.90 mmol/l to 4.01+/-3.00 mmol/l, p < 0.05) but no further increase during the subsequent 45 min. CONCLUSIONS: The new Chiron lactate analyzer is reliable for serial whole blood lactate measurements in an intensive care stat laboratory. Samples should be kept on ice immediately after sampling to minimize in vitro erythrocyte production of lactate.

Acidosis, Lactic↗

The use of maximum SOFA score to quantify organ dysfunction/failure in intensive care. Results of a prospective, multicentre study. Working Group on Sepsis related Problems of the ESICM.

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 > or = 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.

Adolescent↗

Induced hypertension after head injury.

The use of induced hypertension in head injury patients is controversial. We present the case of a 19-year-old man admitted with severe head trauma after a road accident and describe the beneficial effects that increasing arterial blood pressure had on the cerebral perfusion pressure, cerebral blood flow and jugular bulb oxygen saturation in this patient.

Adult↗

Septic shock without documented infection: an uncommon entity with a high mortality.

OBJECTIVES: To determine whether patients with clinically identified infection have the same outcome as patients with apparent sepsis but no identified infectious source. DESIGN: Retrospective analysis of patient data. PATIENTS: All patients treated with septic shock in a 31-bed intensive care unit (ICU) over a 3-year period. RESULTS: Data from 227 patients were analysed. Eighty-seven percent had a clinically identified source of infection. ICU mortality was higher in septic shock patients without a clinically identified source of infection than in those with an identified source of infection (86% versus 66%, p < 0.05). CONCLUSIONS: A small number of patients presenting with septic shock have no clinically identified infection. These patients have a higher mortality rate than patients in whom an infection is identified.

Bacteremia↗