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H Spapen

Publications and source records attributed to H Spapen.

36 records · Page 2Linked to original sources

Effects of N-acetyl-L-cysteine on regional blood flow during endotoxic shock.

We previously reported that N-acetyl-L-cysteine (NAC), an oxygen free-radical scavenger, can increase the oxygen extraction capabilities during endotoxic shock when blood flow is progressively reduced. In the present study, we investigated whether the protective effects of NAC are related to an improvement in regional blood flow following endotoxemia. Fourteen anesthetized, saline-infused and ventilated dogs were divided into two groups: 7 dogs received NAC (150 mg/kg, followed by a 20 mg/kg.h infusion), and the other 7 dogs served as a control time-matching group. Thirty minutes later all the dogs received Escherichia coli endotoxin (2 mg/kg) i.v. A saline infusion was started 30 min after endotoxin challenge to restore pulmonary artery occlusion pressure to baseline and maintain it constant. Regional blood flow was measured by ultrasonic volume flowmeter. In the control group, arterial pressure, left ventricular stroke work index and systemic vascular resistance remained lower than baseline. Mesenteric, renal and femoral arterial blood flow increased but only femoral blood flow returned to baseline levels. In the NAC group, cardiac index and left ventricular stroke work index remained higher and systemic and pulmonary vascular resistance were lower than in the control group. Blood flow in mesenteric, renal and especially femoral arteries was higher than in the control group. Fractional blood flow increased only in the femoral artery. PaO2 and PvO2 had similar courses in the two groups. A higher venous admixture was associated with a higher cardiac index and a lower pulmonary vascular resistance in the NAC group. Oxygen delivery and oxygen-uptake were higher in the NAC-treated than in the control animals throughout the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Nosocomial pansinusitis in orotracheally intubated critically ill patients.

Nosocomial pansinusitis (N P) is most often described in nasotracheally intubated patients with craniocerebral or facial trauma. We retrospectively reviewed its occurrence and complications in the course of prolonged mechanical ventilation in orotracheally intubated patients without maxillofacial or cranial injuries. N P was deemed to be present when (1) CT scan showed opacification and/or air-fluid levels in the maxillary, ethmoid and sphenoid sinuses and (2) aspiration of both maxillary sinuses yielded pus, cultures of which revealed a high concentration of micro organisms. Nosocomial pneumonia and bacteremia were considered related to the N P if the organisms found in the sinus were identical to those recovered from the blood and/or the bronchi. During an 18-month study period, 38 cases of sinusitis were diagnosed. N P was present in 13 patients: 18 organisms (12 Gram-negative, 5 Gram-positive and 1 Candida albicans) were isolated. Pneumonia occurred in 8 patients, 6 with multi-resistant Pseudominas aeruginosa and 2 with methicillin resistant Staphylococcus aureus. Pseudomonas aeruginosa was isolated from the blood, lung and sinus in two patients. This study demonstrates that N P is relatively frequent in patients requiring long-term mechanical ventilation, even in the absence of predisposing factors. N P in these patients is mostly monomicrobial with multi-resistant Pseudomonas aeruginosa and Staphylococcus aureus as the main causative agents.

Adult↗

Sodium nitroprusside does not influence tissue oxygen extraction capabilities during a critical reduction in oxygen delivery.

By its regulating effects on blood vessel tone, nitric oxide (NO) may play an important role in the coupling of oxygen delivery (DO2) to metabolic rate. We reasoned that if endogenous NO synthesis is an important modulator of oxygen extraction ratio (O2ER), then administration of a NO donor will alter oxygen extraction capabilities during a fall in blood flow. We studied the effects of the NO donor, nitroprusside, on the relationship between DO2 and oxygen uptake (VO2) during an acute reduction in DO2 induced by cardiac tamponade. Twenty-one healthy, anaesthetised, mechanically ventilated dogs were randomly divided into 3 groups. Group 1 (n = 7) served as control; Groups 2 and 3 were given sodium nitroprusside at 1.0 microgram/kg.min (n = 7), and 2.5 micrograms/kg.min intravenously (n = 7), respectively. All animals were given normal saline i.v. at a rate of 20 ml/kg.h throughout the study. Cardiac tamponade was induced by bolus injections of normal saline into the pericardial space. In the control animals the critical DO2 (DO2crit) was found at 10.1 +/- 1.5 ml/kg.min and critical O2ER (O2ERcrit) at 63.3 +/- 10.9%. Nitroprusside at the lower dose decreased systemic vascular resistance but did not significantly influence arterial pressure, cardiac output, DO2 or VO2; neither DO2crit nor O2ERcrit was altered (9.3 +/- 2.9 ml/kg.min and 70.4 +/- 20.9%). Nitroprusside at the higher dose induced significant decreases in mean arterial pressure and systemic vascular resistance, but had no significant effect on cardiac output. DO2crit (9.2 +/- 2.0 ml/kg.min) and O2ERcrit (59.8 +/- 13.2%) were similar to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

One week treatment with cimetidine does not attenuate the cortisol response to a short corticotropin test in stable intensive care patients: a prospective, randomized, and controlled study.

Cimetidine is commonly used for stress ulcer prophylaxis in intensive care patients. Cimetidine contains an imidazole structure. Similar drugs have been shown to inhibit steroid synthesis by blocking cytochrome P450-dependent reactions in the adrenal cortex. It is suggested that bolus injections of cimetidine suppress the normal corticosteroid production. This might be deleterious since a decreased cortisol response seems to be associated with increased mortality during chronic severe stress. We therefore performed a prospective, randomized, and controlled study to assess the effect of a short-term continuous infusion of either cimetidine or ranitidine, a non-imidazole H2-pantagonist, upon cortisol secretion in a cohort of hemodynamically stable intensive care patients. Twenty patients were consecutively enrolled following determined inclusion criteria and divided in three treatment groups: 6 controls, 7 cimetidine- and 7 ranitidinetreated subjects. Both cimetidine (1200 mg) and ranitidine (200 mg) were administered by infusion pump over 24 hrs. A short corticotropin test was done within 24 hrs after admission (d0) and repeated 7 days thereafter (d7). On both occasions, plasma cortisol was measured immediately before the test and 30 min afterwards. The three treatment groups presented a normal cortisol response at d0 and d7. Peak cortisol levels after stimulation did not show any significant difference for both the cimetidine and the ranitidine group, either at d0 or at d7. Moreover, this response at d0 and d7 was also not significantly different from the one observed in the controls. From this study we can conclude that one week treatment with conventional intravenous doses of cimetidine does not induce significant alterations of the cortisol response in hemodynamically stable ICU patients.

Adrenocorticotropic Hormone↗

Prostaglandin E1 increases oxygen extraction capabilities in experimental sepsis.

By its microvascular and anti-inflammatory actions, prostaglandin E1 (PGE1) has been suggested both in animal models and in humans to have a therapeutic value in sepsis. To investigate whether PGE1 could improve the oxygen extraction capabilities in severe sepsis, our study focused on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow induced by cardiac tamponade in endotoxic dogs. Thirty anesthetized, ventilated dogs were divided into three groups. A first group (N = 10) served as a control receiving 20 ml/kg/hr of saline intravenously. A second group (N = 10) received PGE1 at 100 ng/kg/min along with the same saline infusion. A third group (N = 10) received the same dose of PGE1 with only 1 ml/kg/hr of saline. Thirty minutes after the initiation of this therapy, Escherichia coli endotoxin (2 mg/kg) was injected in each dog. In each group, the administration of PGE1, fluids, or both was continued throughout the study. Tamponade was then induced by repeated bolus injections of warm saline into the pericardial space. Steady-state measurements of VO2 (derived from the expired gases) and DO2 (the product of cardiac index and oxygen content) were obtained sequentially after each saline injection. The administration of PGE1 + fluids resulted in significant increases in stroke volume, cardiac index, and DO2 and reductions in systemic and pulmonary vascular resistance. Stroke volume and cardiac index were lower in the PGE1 alone than in the PGE1 + fluids group. The VO2 levels at critical DO2 (DO2crit) were identical. However, DO2crit, which was 12.2 +/- 2.8 ml/kg/min in the control group, was significantly decreased to 9.8 +/- 2.0 ml/kg/min in the PGE1 + fluids and to 9.3 +/- 2.7 ml/kg/min in the PGE1 alone group (both P < 0.05). Critical oxygen extraction ratio (O2ERcrit) which was 47 +/- 14% in the control group, was increased to 63 +/- 16% in the PGE1 + fluids group and to 61 +/- 17% in the PGE1 alone group (both P < 0.05). To investigate whether PGE1 also improves oxygen extraction capabilities in the absence of endotoxin, a second series of experiments was performed in 14 dogs, receiving saline alone (Control, N = 7) or plus PGE1 at 100 ng/kg/min (PGE1, N = 7). DO2crit was 10.7 +/- 2.9 ml/kg/min in the PGE1 group vs 10.1 +/- 1.8 ml/kg/min in the control group (NS). O2ERcrit tended to be higher in the PGE1 group than that in the control group (68 +/- 13% vs 60 +/- 15%, P = 0.054).(ABSTRACT TRUNCATED AT 400 WORDS)

Alprostadil↗

Effects of dobutamine and norepinephrine on oxygen availability in tamponade-induced stagnant hypoxia: a prospective, randomized, controlled study.

OBJECTIVES: To explore the effects of dobutamine and norepinephrine on the global cardiovascular response and on the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during an acute reduction in blood flow associated with tamponade. DESIGN: Prospective, randomized, controlled acute intervention study. SETTING: University intensive care unit (ICU) laboratory. SUBJECTS: Twenty healthy, anesthetized mongrel dogs, weighing 19 to 28 kg. INTERVENTIONS: Six dogs served as control, seven dogs were given 10 micrograms/kg/min of dobutamine and another seven dogs were given 1 microgram/kg/min of norepinephrine. Data were collected at graded incremental levels of intrapericardial pressure. MEASUREMENTS AND MAIN RESULTS: VO2 was derived from expired gas analysis and DO2 was calculated from the product of thermodilution cardiac index and arterial oxygen content. In each animal, two catheters were inserted into the pericardium to induce tamponade by saline infusion and to measure the intrapericardial pressure. The critical Do2 value, below which VO2 decreased, was found at 9.4 +/- 1.3 mL/kg/min in the control animals. When DO2 decreased to below this critical value, lactic acidosis developed. Dobutamine and norepinephrine, at the dose that was administered, significantly increased cardiac index and DO2. Critical DO2 was slightly higher in the treated than in the control animals (12.1 +/- 1.6 mL/kg/min in dobutamine and 13.2 +/- 0.9 mL/kg/min in norepinephrine, NS). VO2 at critical DO2 was significantly higher in the treated groups than in the control group (7.7 +/- 1.1 mL/kg/min in the dobutamine group and 7.9 +/- 0.9 mL/kg/min in the norepinephrine group vs. 5.4 +/- 0.4 mL/kg/min in control, both p < .01). There was no significant difference in the critical oxygen extraction ratio and the slope of the supply-dependent line between the three groups. In dobutamine-treated animals, cardiac index, DO2, and VO2 were better maintained for any intrapericardial pressure than in the other groups. Critical intrapericardial pressure, at which VO2 started to decrease, was significantly higher in the dobutamine-treated group than in the control group (13.8 +/- 2.3 vs. 9.3 +/- 1.2 mm Hg, p < .05). At critical DO2, the mean blood lactate concentration was also lower in the dobutamine-treated animals than in the other animals (2.1 +/- 0.3 vs. 4.1 +/- 0.7 mmol/L in control and 3.8 +/- 0.4 mmol/L in the norepinephrine group, both p < .05). CONCLUSIONS: During low-flow states associated with tamponade, both dobutamine and norepinephrine at the dose used increased cardiac index, DO2, and VO2, but dobutamine delayed the onset of tissue hypoxia by further increasing blood flow and oxygen availability. In the conditions of the present study, neither agent significantly influenced the oxygen extraction capabilities of the body.

Animals↗

Pentoxifylline improves the tissue oxygen extraction capabilities during endotoxic shock.

Pentoxifylline (PTX), a xanthine derivative used in the treatment of circulatory insufficiency, has been found to have protective effects in different models of sepsis. We hypothesized that this drug might improve the cellular oxygen availability following endotoxin challenge by increasing oxygen delivery (DO2) and/or tissue oxygen extraction. The oxygen extraction capabilities were studied during a reduction in blood flow induced by cardiac tamponade. Fourteen anesthetized, ventilated, and paralyzed dogs, received intravenous 2 mg/kg of Escherichia coli endotoxin followed by a continuous infusion of 20 ml/kg.h of saline. 30 min later tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Seven dogs were pretreated with PTX as an intravenous bolus of 20 mg/kg, followed by a continuous infusion at 20 mg/kg.h, and the other seven dogs served as a control group. PTX largely attenuated the systemic and pulmonary vasoconstriction observed in the control group and resulted in significant increases in cardiac index, DO2 and oxygen consumption (VO2). PTX also improved ventilation/perfusion matching in the lungs as indicated by a higher PaO2 and PvO2 and a lower venous admixture than in the untreated group during cardiac tamponade (both p < .05). In addition, the critical DO2 (DO2 crit) was lower and the critical oxygen extraction ratio was higher in the PTX treated than in the control group (9.1 +/- 1.8 vs. 11.6 +/- 2.4 ml/kg.min, and 70.6 +/- 14.0 vs. 49.3 +/- 14.6%, both p < .05). The VO2/DO2 dependency slope was also steeper in the PTX-treated than in the control group (.80 +/- .28 vs. .43 +/- .19, p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Protective effects of N-acetyl-L-cysteine in endotoxemia.

Because oxygen free radicals have been implicated in the endothelial cell damage and in the myocardial depression occurring during severe sepsis, we investigated whether N-acetyl-L-cysteine (NAC) could influence the oxygen extraction capabilities during an acute reduction in blood flow induced by cardiac tamponade after endotoxin challenge. Sixteen anesthetized, saline-infused, and ventilated dogs received Escherichia coli endotoxin (2 mg/kg) 30 min before tamponade was induced by repeated bolus injections of warm saline into the pericardial space. Thirty minutes before endotoxin administration, nine dogs received NAC (150 mg/kg, followed by a 20 mg.kg-1.h-1 infusion); the other seven dogs served as a control group. The NAC group maintained higher cardiac index, oxygen delivery (DO2), and left ventricular stroke work index, but lower systemic and pulmonary vascular resistance, than the control group. The oxygen uptake (VO2) levels at critical DO2 (DO2crit) were identical in the two groups. However, DO2crit was significantly lower in the NAC than in the control group (8.1 +/- 1.7 vs. 10.8 +/- 1.8 ml.kg-1.min-1, P < 0.01). Critical oxygen extraction ratio and the slope of the VO2-to-DO2-dependent line were higher in the NAC than in the control group (72 +/- 14 vs. 53 +/- 15% and 0.80 vs. 0.56, respectively; both P < 0.05). The peak lactate and the maximal tumor necrosis factor (TNF) levels were lower in the NAC than in the control group (5.2 +/- 0.4 vs. 7.6 +/- 0.4 mM, and 0.14 +/- 0.03 vs. 1.21 +/- 0.58 ng/ml, respectively; both P < 0.01). NAC significantly increased glutathione peroxidase activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcysteine↗

Systemic oxygen extraction can be improved during repeated episodes of cardiac tamponade.

We used a tamponade model to study the relationship between oxygen uptake (VO2) and oxygen delivery (DO2) during successive, reversible decreases in blood flow. In 7 pentobarbital-anesthetized and mechanically ventilated dogs, a catheter was introduced via a left thoracotomy into the pericardium to inject and to withdraw saline. Each experiment consisted of three steps. First, cardiac output was reduced by successive pericardial fluid injections until 4 to 6 data points were obtained in the dependent region of the VO2/DO2 plot (step 1). Second, cardiac output was restored by progressive withdrawal of pericardial fluid (step 2). Third, cardiac output was lowered again by reinjection of fluid into the pericardium until death (step 3). Expired gases were collected for determination of VO2. In each animal, critical DO2 (DO2crit), below which VO2 became DO2 dependent, was determined from a plot of VO2 versus DO2. When releasing tamponade, VO2 was restored to baseline. For the 3 steps, DO2crit were 10.5 +/- 2.2 mL/kg/min in step 1, 9.8 +/- 1.8 mL/kg/min in step 2, and 8.3 +/- 1.9 mL/kg/min in step 3 (P < .01 v step 1; P < .05 v step 2, respectively). There was no significant difference in VO2 at DO2crit for the three steps. Hence, critical oxygen extraction ratio (ERO2crit) increased from 60% +/- 12% in step 1 to 64% +/- 11% in step 2 (not significant) and to 73% +/- 12% in step 3 (P < .01). The VO2/DO2 dependency slope was also steeper in step 3 than in step 1 (0.77 +/- 0.31 v 0.54 +/- 0.20, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Acidosis, Lactic↗

Pulmonary arterial hypertension in sepsis and the adult respiratory distress syndrome.

Pulmonary arterial hypertension, defined as a mean pulmonary artery pressure exceeding 20 mmHg has been observed both in experimental animal and human sepsis, even before development of the adult respiratory distress syndrome. In this article we review several mechanisms that have been invoked for the pulmonary arterial hypertension associated with sepsis (and the adult respiratory distress syndrome): obstruction of the pulmonary microcirculation with microthrombi composed of platelets and leukocytes, and active pulmonary vasoconstriction induced by the autonomous nervous system, hypoxia or vasoactive humoral factors ("mediators"). Some of these mediators, in particular serotonin and arachidonic acid metabolites have been the subject of substantial research and therapeutic manipulation. Since pulmonary arterial hypertension imposes an increased afterload to the right ventricle and because right ventricular dysfunction appears to be a major determinant of the outcome of sepsis, the study of the mechanisms involved in pulmonary arterial hypertension may lead to improved management of sepsis and septic shock.

Humans↗

A case of concomitant ethanol and strychnine intoxication.

The authors describe a patient presenting with both ethanol intoxication and important strychnine poisoning. The diagnosis and treatment of strychnine poisoning are discussed. The authors emphasize the need of careful urine screening for drugs and toxic products in all ethanol-intoxicated patients.

Aged↗

Pre- and peroperative diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia type 2a.

A 37-year-old woman with a multiple endocrine neoplasia type 2a underwent bilateral adrenalectomy and total thyroidectomy with parathyroidectomy in 1977. The left-sided pheochromocytoma was considered to be malignant. Seven yr after the initial operation, an enhanced urinary excretion-ratio of N-methyladrenaline/adrenalin suggested the possible presence of either persistent or metastatic pheochromocytoma Iodine-123-labeled metaiodobenzylguanidine scintigraphy (I-123 MIBG) showed a hot spot in the right lung. However, repeated chest-X-rays and computed tomographic scanning of the thorax remained negative. Anatomical localization of the lesion was finally obtained with magnetic resonance imaging. The surgical removal of the small pheochromocytoma was guided by the gamma-ray emission of I-123 MIBG administered iv before the operation. This case report illustrates the usefulness of new analytical methods and of new imaging techniques in the diagnosis and management of metastatic pheochromocytoma.

Adult↗

Treatment of malignant pericardial tamponade with sclerosis induced by instillation of bleomycin.

Five patients with pericardial tamponade of neoplastic origin were treated by pericardiocentesis, drainage and local instillation of bleomycin. The pericardial effusion was adequately controlled in all patients. Survival was influenced not by the pericardial involvement, but by the natural evolution of the tumour. Side effects were minimal. The technique of drainage and bleomycin sclerosis is simple, safe, effective and inexpensive for the management of a malignant pericardial tamponade, providing all precautions necessary for diagnosis and pericardiocentesis are adequately taken.

Aged↗