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J Boldt

Publications and source records attributed to J Boldt.

At least 145 records · Page 8Linked to original sources
PubMed1996

Does long-term continuous administration of pentoxifylline affect platelet function in the critically ill patient?

OBJECTIVE: The methylxanthine derivative pentoxifylline (PTX) is one of those promising substances which are under current investigation to modify or limit inflammatory response. Anti-aggregation activity has also been described that may contribute to the beneficial effects of this substance. Long-term effects on platelet function have not been elucidated yet. DESIGN: Prospective, randomized study. SETTING: Clinical investigation on a surgical intensive care unit of a university hospital. PATIENTS: 26 trauma patients and 26 patients suffering from sepsis secondary to major operations were consecutively studied. INTERVENTIONS: The patients prospectively received either 1.5 mg/kg per h pentoxifylline continuously for 5 days (after a loading dose of 600 mg) (trauma-PTX, n = 13; sepsis-PTX, n = 13) or saline solution as placebo (trauma-control; n = 13; sepsis-control, n = 13). MEASUREMENTS: On the day of admission (trauma patients) or day of the diagnosis of sepsis and at 12:00 p.m. during the next 5 days, platelet aggregation induced by adenosine diphosphate (ADP 2.0 mumol/l), collagen (4 microliters/ml), and epinephrine (25 mumol/l) was determined by a turbidimetric method from arterial blood samples. Standard coagulation screen was also monitored. MAIN RESULTS: In untreated trauma and sepsis patients, maximum platelet aggregation induced by all three agonists decreased during the first few days after inclusion in the study [trauma: ADP - 17.1 +/- 8.0 rel% (% change from baseline); sepsis: ADP -26.1 +/- 5.6 rel%]. In due course, maximum platelet aggregation recovered, reaching the baseline value or even exceeding it (trauma patients). In the PTX-treated patients, platelet aggregation was significantly less impaired (sepsis group: ADP -4.4 +/- 3.3 rel%) or even increased beyond baseline values in the first few days of the study (trauma group: ADP 16.1 +/- 8.0 rel%). Fibrinogen plasma levels were lower in the non-treated control groups (p < 0.05) than in the PTX groups. CONCLUSIONS: Continuous infusion of PTX for 5 days did not impair platelet function in critically ill patients. In both trauma and sepsis patients, the usual deterioration in platelet function was even attenuated, which may be due to the effects of PTX on cytokine release (e.g., reduction in tumor necrosis factor and interleukin-1), improvement in microcirculation, or additional fibrinolytic effects.

Adult↗
PubMed1996

Circulating adhesion molecules in the critically ill: a comparison between trauma and sepsis patients.

OBJECTIVE: The time course of circulating adhesion molecules was monitored in traumatized and sepsis patients. DESIGN: Prospective, descriptive. SETTING: A surgical intensive care unit of a university hospital. PATIENTS: A total of 30 consecutive critically ill patients suffering either from trauma (n = 15) or postoperative sepsis (n = 15). INTERVENTIONS: All patients were on continuous analgo-sedation and mechanical ventilation. MEASUREMENTS AND RESULTS: From arterial blood samples, plasma levels of soluble adhesion molecules [endothelial leukocyte adhesion molecules (sELAM-1), intercellular adhesion molecule-1 (sICAM-1)], and vascular cell adhesion molecule-1 (sVCAM-1) were measured on the day of admission (trauma patients) or on the day of diagnosis of sepsis (= baseline values), and during the following 5 days. In the trauma group, sELAM-1 (57.9 +/- 11.0 ng/ml) and sVCAM-1 (698 +/- 93 ng/ml) were within normal ranges at baseline, whereas they were markedly elevated in the sepsis group (sELAM-1: 340 +/- 95 ng/ml; sVCAM-1; 1,042 +/- 449 ng/ml). In the sepsis patients, sELAM-1 significantly decreased and sVCAM-1 increased, but remained almost unchanged in the trauma patients. Non-survivors showed markedly elevated plasma levels of sELAM-1 and sVCAM-1. sICAM-1 was elevated in both groups at baseline and was higher in the sepsis group (1,266 +/- 261 ng/ml) than in the trauma group. In the septic patients, sICAM-1 increased further (2,022 +/- 609 ng/ml) and remained unchanged in the trauma group. All non-survivors showed sICAM-1 plasma levels of > 800 ng/ml. CONCLUSIONS: Endothelial damage may result in multiple-organ dysfunction syndrome. Adhesion molecules are considered to be a cornerstone in this process. Trauma patients showed lower plasma levels of circulating adhesion molecules than did sepsis patients indicating more pronounced (inflammatory related) endothelial activation or damage in sepsis. Therapeutic modulation of circulating adhesion molecules may be of benefit to the patients outcome and therefore warrants further study.

Adult↗
PubMed1996

Success rates following intracytoplasmic sperm injection are improved by using ZIFT vs IVF for embryo transfer.

PURPOSE: The purpose of this study was to analyze whether the mode of embryo transfer (ZIFT vs IVF) affected the outcome in intracytoplasmic sperm injection (ICSI) cycles. METHODS AND RESULTS: Eighty-two ICSI cycles (42 ZIFT and 40 IVF) were analyzed. Several variables, including patient age and weight, numbers of mature eggs collected, injected, and fertilized, fertilization rate, number of fertilized eggs obtained per cycle, numbers of zygotes/embryos transferred, clinical pregnancy rate, and implantation rate, were compared. Mean patient age and weight were identical. The mean number of mature eggs collected and injected and fertilization rate were significantly higher in the ZIFT group, however, the mean numbers of zygotes/embryos transferred were identical. The clinical pregnancy and implantation rates in ZIFT cycles (52.3 and 23.2% respectively) were significantly higher than in IVF cycles (17.5 and 9.7%). CONCLUSIONS: These data suggest that ZIFT is the more appropriate method for transfer of ICSI-derived embryos.

Adult↗
PubMed1996

[The in vitro effect of alpha-2 agonists on thrombocyte function and density of thrombocyte alpha-2 receptors].

UNLABELLED: alpha 2-Agonists are being used increasingly in anaesthesia and intensive care medicine because of their antihypertensive, analgesic and sedative properties. Platelets bear alpha 2-receptors on the cell surface. Stimulation of these receptors by agonists induces platelet aggregation. The present study examined whether in vitro incubation of blood with the alpha 2-agonists clonidine and dexmedetomidine decreases alpha 2-receptor density and hereby influences platelet aggregation. METHODS: Whole blood of 20 healthy volunteers was incubated over 24 h at 37 degrees C with 1 ng/ml clonidine or 1 or 10 ng/ml dexmedetomidine. Induced platelet aggregation was determined by means of turbidometry. Epinephrine (22 mumol/l) or collagen (20 mg/l) served as inductors. The density of alpha 2-receptors was measured in radioligand assays with 3H-Yohimbine. Phentolamine was used to assess unspecific binding. The data were analyzed with an analysis of variance. RESULTS: Neither 1 ng/ml clonidine nor 1 ng/ml dexmedetomidine altered platelet aggregation or alpha 2-receptor density in comparison with the control sample. As a major result we found that 10 ng/ml dexmedetomidine caused a significant (P < 0.05) reduction in epinephrine-induced platelet aggregation (16.0 +/- 5.4%, n = 20, mean +/- SEM) compared with the control (46.0 +/- 1.3%, n = 20). alpha 2-Receptor density was not any different from the control. CONCLUSIONS: This in vitro study showed that clinically relevant concentrations of 1 ng/ml clonidine or dexmedetomidine did not alter platelet aggregation or alpha 2-receptor density, even after 24 h exposure. However, 10 ng/ml dexmedetomidine was found to diminish significantly epinephrine-induced platelet aggregation, but did not change alpha 2-receptor density. This result showed that desensitization of platelet aggregation can occur without quantitative changes in alpha 2-receptors.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1996

[Cost aspects in anesthesia. Propofol versus isoflurane anesthesia].

UNLABELLED: Cost control is no longer an option, but a necessity. Propofol anaesthesia is expensive, however, the true differences in comparison to volatile anaesthetics (isoflurane) are not known. METHODS: Sixty patients undergoing either thyroidectomy (n = 30) or laparoscopic cholecystectomy (n = 30) were randomly divided into 3 groups of 20 patients. In group I propofol and fentanyl were used for anaesthesia, in group II isoflurane ('standard' isoflurane anaesthesia), and in group III isoflurane using a low-flow system (fresh gas flow 2 l/min) was given. All patients were ventilated using 70% N2O in oxygen. Vecuronium was used in all cases for muscle relaxation. Isoflurane consumption was measured by weighing the isoflurane vaporizer. RESULTS: Biometric data and time of administration of the anaesthetic were similar in the three groups. Propofol patients stayed significantly shorter than isoflurane patients in the postanaesthesia care unit (PACU). Costs of additional drugs (antiemetics, analgesics) in the PACU were least in the propofol patients. Costs were without differences between the propofol (78.30 DM/patient) and 'standard' isoflurane groups (81.69 DM/patient). Patients in group III showed the lowest overall costs (57.46 DM/patient) (P < 0.05). CONCLUSION: A climate of cost-consciousness and cost-containment prevails at the present time. The costs of propofol and 'standard' isoflurane anaesthesia were without differences; however, isoflurane used in a low-flow system had the lowest cost in this study. Doubts are justified, however, as to whether the choice of anaesthetic agents may considerably lower the costs of an anaesthesia department.

Adult↗
PubMed1996

Normothermic versus hypothermic cardiopulmonary bypass: do changes in coagulation differ?

BACKGROUND: The differences between hypothermic and normothermic cardiopulmonary bypass (CPB) on platelet function and endothelial-related coagulation (eg, the thrombomodulin/protein C/protein S system) should be investigated. METHODS: According to a randomized sequence, 30 patients undergoing aortocoronary bypass grafting underwent either hypothermic (rectal temperature, 27 degrees C to 28 degrees C, n = 15) or normothermic CPB (rectal temperature, more than 35 degrees C, n = 15). Arterial blood samples were taken after induction of anesthesia (baseline values), before, during, and immediately after CPB, 5 hours after CPB, and on the morning of the first postoperative day. Circulating thrombomodulin, (free) protein S, protein C, and thrombin/antithrombin III complex were measured from these samples. Platelet function was assessed by aggregometry (turbidometric technique) induced by adenosine diphosphate (2 mumol/L), collagen (4 micrograms/L), and epinephrine (25 mumol/L). RESULTS: Hypothermic patients showed a significantly higher blood loss and need for homologous blood than the normothermic patients. Thrombomodulin plasma level increased more in the hypothermic (from 28 +/- 5 ng/mL to 60 +/- 10 ng/mL) than in the normothermic group (from 28 +/- 7 ng/mL to 41 ng/mL); p < 0.05). Both protein C and (free) protein S were reduced significantly in the hypothermic (protein C, from 88% +/- 25% to 60% +/- 11%; protein S, from 71% +/- 10% to 40% +/- 8%) than in the normothermic patients. Platelet aggregation was significantly more decreased in the hypothermic (adenosine diphosphate, maximum decrease by -43% relative to baseline) than in the normothermic patients (adenosine diphosphate, maximum decrease by -22% relative to baseline). In the hypothermic CPB group, platelet aggregation had recovered incompletely, whereas in the normothermic patients platelet aggregation even slightly exceeded baseline values. CONCLUSIONS: Hypothermic CPB resulted in more pronounced alterations of platelet aggregation and endothelial-related coagulation than normothermic CPB. Plasma levels of soluble thrombomodulin were more increased in hypothermic than in normothermic CPB indicating more extensive endothelial damage or activation associated with hypothermic CPB.

Aged↗
PubMed1996

Endothelin plasma levels during heart surgery: influence on pulmonary artery pressure?

OBJECTIVE: Some studies found endothelin-1 to be a trigger for pulmonary hypertension. Endothelin-1 is an endothelial derived substance with generally vasoconstrictive properties, but probably vasodilatory effects on pulmonary arteries. The aim of the present study was to look for influences of endothelin-1 plasma values on pulmonary artery pressure. METHODS: Endothelin-1 levels during and after cardiac surgery and correlations to pulmonary artery pressure were tested in 10 control patients and 21 patients with pulmonary hypertension (mean pulmonary arterial pressure > 20 mmHg, systolic pulmonary arterial pressure > 30 mmHg). RESULTS: According to endothelin-1 values before anaesthesia (normal value below 4 pg/ml) patients with pulmonary hypertension could be divided into a "high endothelin-1" (10 patients, mean 8.25 +/- 2.06 pg/ml) and a "normal endothelin-1" (11 patients, mean 2.13 +/- 0.86 pg/ml) subgroup (p < 0.01). Values of the "high endothelin-1" group decreased until end of operation (from 7.58 +/- 2.35 to 2.95 +/- 1.44 pg/ml, n = 6) when pulmonary artery pressure returned to normal. Otherwise they slightly increased (from 9.43 +/- 2.24 to 11.07 +/- 1.96 pg/ml, n = 4). Levels of the "normal endothelin-1" group increased (to 2.55 pg/ml). Endothelin-1 values peaked on the intensive care unit (ICU) in all patients. Baseline endothelin-1 and systolic pulmonary artery pressure values correlated well with each other (r = 0.73, p < 0.001). Endothelin-1 decreased after extracorporeal circulation in all patients in whom pulmonary artery pressure tended to normalise, whereas no rise in pulmonary artery pressure paralleled the marked increase in endothelin-1 on the ICU. Vasodilatory effects of endothelin on pulmonary arteries can attribute to this course. CONCLUSIONS: Endothelin-1 seems not to trigger pulmonary hypertension but rather to vasodilate pulmonary vasculature.

Aged↗
PubMed1996

RETRACTED: Cardiorespiratory changes in patients undergoing pulmonary resection using different anesthetic management techniques.

OBJECTIVE: Pulmonary resection may be associated with considerable alterations of the cardiorespiratory system. The ideal anesthetic regimen for these patients is not yet definitely determined. DESIGN: Prospective, randomized study. SETTING: Single-institutional, clinical investigation in a thoracic anesthesia department of a university hospital. PARTICIPANTS: Fifty consecutive patients scheduled for elective thoracic surgery for lung cancer. INTERVENTIONS: In 20 patients undergoing lobectomy, fentanyl/propofol/nitrous oxide/vecuronium anesthesia was used, and extubation was planned immediately after surgery (group 1A, early extubation). Another 20 patients with lobectomy were anesthetized during fentanyl/midazolam/vecuronium, and they were extubated in the intensive care unit (ICU) (group 1B, late extubation). Ten patients underwent pneumonectomy (extubation planned in the ICU) (group 2, pneumonectomy). Patients of groups 1A and 1B were selected according to a randomized sequence. MEASUREMENTS AND MAIN RESULTS: Extensive hemodynamic monitoring was performed using a pulmonary artery catheter by which right ventricular hemodynamics (right ventricular ejection fraction [RVEF], right ventricular end-systolic, and end-diastolic volumes) were additionally measured. Measurements were performed after induction of anesthesia (supine position, baseline values), before surgery (lateral position), 30 minutes after one-lung ventilation (OLV) was induced, at the end of surgery (supine position), 2 hours after surgery (in ICU), and on the morning of the first postoperative day. Pneumonectomy resulted in an increase in the pulmonary wedge pressure (from 12.2 +/- 2.9 to 18.3 +/- 3.8 mmHg) and a deterioration in right ventricular hemodynamics with a decrease in RVEF from 40.6 +/- 3.4% to 28.8 +/- 4.3% at the end of surgery. These changes were also seen on the morning of the first postoperative day. PaO2/FI02, Qs/Qt, VO2I, and DO2I were also significantly different between pneumonectomy and lobectomy patients. Intraoperatively, patients of group 1A and 1B showed almost similar cardiorespiratory data. During OLV, PaO2/FIO2 was significantly less reduced in group 1A (to 292 +/- 98 mmHg) than in group 1B (to 200 +/- 120 mmHg). Postoperatively, patients of group 1A were orientated, and physiotherapy could be started early. No relevant differences with regard to cardiorespiratory parameters were observed between group 1A and group 1B in the postoperative period until the first postoperative day. CONCLUSIONS: In comparison with lobectomy patients, pneumonectomy resulted in more pronounced and sustained deterioration in right ventricular hemodynamics. The kind of anesthesia regimen did not influence most of the cardiorespiratory parameters intraoperatively, except for Qs/Qt, which was least compromised in the propofol patients during OLV. Early extubation could safely be performed in the lobectomy patients anesthetized with propofol without showing any negative cardiorespiratory effects.

Adult↗
PubMed1996

RETRACTED: Hypothermic versus normothermic cardiopulmonary bypass: influence on circulating adhesion molecules.

OBJECTIVE: Cardiopulmonary bypass (CPB) may result in a whole-body inflammatory response with the risk of subsequent development of organ failure. Leukocyte-endothelial binding followed by neutrophil migration appear to play a central role. This process is markedly influenced by adhesion molecules. Whether plasma levels of circulating adhesion molecules are beneficially influenced by hypothermic CPB was studied in patients undergoing either hypothermic or normothermic CPB. DESIGN: Prospective, randomized study. SETTING: Single-Institutional, clinical investigation in a cardiac anesthesia department of a university hospital. PARTICIPANTS: 30 patients scheduled for elective aortocoronary artery bypass grafting. INTERVENTIONS: The patients were prospectively and randomly divided into two groups: group 1 underwent hypothermic CPB (rectal temperature 27 to 28 degrees C; n = 15) and group 2 normothermic CPB (rectal temperature > 36 degrees C; n = 15). MEASUREMENTS AND MAIN RESULTS: Plasma levels of circulating (soluble) adhesion molecules (endothelial leukocyte adhesion molecules [sELAM-1], vascular cell adhesion molecule-1 [sVCAM-1], intercellular adhesion molecule-1 [sICAM-1], and granule membrane protein 140 [sGMP-140]) were measured from arterial blood samples using enzyme-linked immunosorbent assays (ELISA) after induction of anesthesia (= baseline values), after weaning from bypass, at the end of surgery, 5 hours after the end of CPB, and on the morning of the first postoperative day. Mean rectal temperature of group 1 was 27.2 +/- 0.4 degrees C and 36.7 +/- 0.4 degrees C in group 2. In both groups, plasma levels of sELAM-1 were significantly higher than baseline only 5 hours after CPB. sICAM-1 increased until the first postoperative day (group 1: +35%; group 2: +37%) without, however, exceeding the normal range. sVCAM-1 plasma levels increased after CPB (group 1: +56%; group 2: +40%). At the end of surgery and 5 hours after CPB, sGMP-140 plasma levels were significantly higher in the hypothermic (increase from 301 +/- 34 to 582 +/- 57 ng/mL) than in the normothermic patients (increase from 310 +/- 45 to 480 +/- 32 ng/mL). On the first postoperative day, both groups showed similar, significantly elevated plasma levels of sGMP-140. CONCLUSIONS: Plasma levels of circulating adhesion molecules sELAM-1, sICAM-1, and sVCAM-1 did not differ between hypothermic and normothermic CPB, indicating no differences in endothelial activation between the two groups. Only sGMP-140 plasma levels were increased more after hypothermic CPB. Additional influences of hypothermia on the coagulation system might have contributed to the higher sGMP-140 plasma levels of these patients. The definite role of circulating adhesion molecules in cardiac surgery patients remains to be elucidated.

Aged↗
PubMed1996

Influence of different volume therapy regimens on regulators of the circulation in the critically ill.

Various vasoactive substances are involved in the regulation of the macro- and microcirculation. We have investigated if these regulators change during long-term volume therapy with human albumin (HA) or hydroxyethylstarch solution (HES) in trauma and sepsis patients. To maintain pulmonary capillary wedge pressure (PCWP) at 10-15 mm Hg, either 20% HA (HA-trauma, n = 14; HA-sepsis, n = 14) or 10% low-molecular weight HES solution (HES-trauma, n = 14; HES-sepsis, n = 14) were infused for 5 days, otherwise patient management did not differ between the two groups (trauma/sepsis). Mean arterial pressure (MAP), heart rate (HR), PCWP and cardiac index (CI) were monitored in all patients. Liver function was assessed using the monoethylglycinexylidide (MEGX) test, and gastric intramucosal pH (pHi) was monitored by tonometry to assess splanchnic perfusion. Plasma concentrations of vasopressin, endothelin-1, adrenaline, noradrenaline, atrial natriuretic peptide and 6-keto-prostaglandin F1 alpha were measured from arterial blood samples. All measurements were carried out on the day of admission to the intensive care unit (trauma patients) or on diagnosis of sepsis, and daily over the next 5 days at 12:00. MAP, HR and PCWP did not differ between the corresponding subgroups (trauma/sepsis). Cl increased significantly more in the HES than in the HA groups. pHi and MEGX plasma concentrations did not differ in the trauma patients throughout the study. Both were lower than normal in the sepsis groups and increased more markedly in the HES than in the albumin-treated patients (P < 0.05). In the trauma patients, concentrations of all vasoactive regulators were very similar in both groups. In both sepsis groups, vasopressors (vasopressin, endothelin-1, noradrenaline and adrenaline) were significantly increased above normal at baseline and decreased more markedly in HES than in HA patients. Concentrations of atrial natriuretic peptide increased only in the HA patients (from 159 (SD 31) to 215 (38) pg ml-1 on day 2). Plasma concentrations of 6-keto-prostaglandin F1 alpha decreased significantly only in the HES sepsis patients (from 112 (25) to 47 (15) pg ml-1).

Adult↗
PubMed1996

The effects of albumin versus hydroxyethyl starch solution on cardiorespiratory and circulatory variables in critically ill patients.

Sufficient intravascular fluid therapy is of major importance in the treatment of the critically ill patient. The present study assessed whether the cardiorespiratory response of long-term volume replacement with low-molecular weight (LMW) hydroxyethyl starch solution (HES) differs from that of human albumin (HA). According to a randomized sequence, 30 trauma patients (injury severity score [ISS] between 15 and 30) and 30 sepsis patients (secondary to major general surgery) received either 10% HES (mean molecular weight 200,000 daltons; HES trauma [n = 15], HES sepsis [n = 15]) or human albumin 20% (HA trauma [n = 15], HA sepsis [n = 15]) over 5 days to keep pulmonary capillary wedge pressure (PCWP) between 12 and 18 mm Hg. Cardiorespiratory variables were measured by a pulmonary artery catheter on the day of inclusion into the study and daily during the next 5 days. Gastric intramucosal pH (pHi) was measured by tonometry. Central venous pressure and PCWP were comparable within the subgroups (trauma/sepsis) throughout the entire study period. In the trauma patients, cardiac index (CI), oxygen consumption index (VO2I), and oxygen delivery index (DO2I), significantly increased only in the HES-treated patients. In the sepsis patients, CI, VO2I, and DO2I increased and remained higher than baseline only in the HES group (P < 0.01). Right ventricular ejection fraction (RVEF) was reduced (< 40%) in the HA patients and increased only in the HES patients (from 34% +/- 4% to 42% +/- 3%; P < 0.05). pHi remained normal (> 7.35) in both trauma groups and in the HES-treated sepsis patients. In the HA sepsis group, pH, decreased (> 7.20) within the study period (7.15 +/- 0.12 on Day 4), indicating deteriorated splanchnic perfusion. We conclude that long-term intravascular fluid therapy with HA in traumatized and sepsis patients has no advantages in comparison to LMW-HES. In both groups, volume replacement with HES even resulted in improved systemic hemodynamics. Decrease in pHi in the sepsis patients was blunted by HES infusion indicating improved splanchnic perfusion by this regimen of volume therapy.

Adult↗
PubMed1996

Platelet function and adrenoceptors during and after induced hypotension using nitroprusside.

BACKGROUND: Hypotension induced by sodium nitroprusside can minimize intraoperative blood loss. The release of endogenous catecholamines can influence adrenoceptors of platelets and thus might change the ability of platelets to aggregate. METHODS: Forty patients undergoing nasal septum, tympanoplastic, or sphenoid sinus surgery were randomly divided into two groups, those having controlled hypotension (A) and those serving as controls (B). Blood samples were drawn before the operation, after induction of anesthesia, 1 h after the start of the operation, and on the day after surgery. RESULTS: Epinephrine-induced platelet aggregation only increased in the controls on the day after surgery (A: from 49 +/- 25% to 47 +/- 29%; B: from 53 +/- 24% to 72 +/- 14%; mean +/- SD; P < 0.01). Spontaneous platelet aggregation increased in the controls from a median of 1.2 omega/h to 2.4 during the operation and 2.9 on the day after surgery but not after hypotension. On the day after surgery, alpha 2 receptors reached their maximum (A: 238 +/- 164; B: 234 +/- 80 per platelet). During the operation, the norepinephrine concentrations were significantly greater in group A (median, 419 pg/ml) than in group B (median, 217 pg/ml; P < 0.05). Blood loss was greater in the controls (A: 180 +/- 75; B: 379 +/- 120 ml; P < 0.05). CONCLUSIONS: Controlled hypotension using sodium nitroprusside reduces epinephrine-induced and spontaneous platelet aggregation. Even on the day after hypotension, the usual postoperative reactive increase in platelet aggregation did not occur. These results may be explained by the direct effect of nitroprusside on platelets, the augmented stress response, lower shear stress on platelets due to the lower blood pressure, or the decreased blood loss compared with the controls.

Adult↗
PubMed1996

Influence of different volume therapies and pentoxifylline infusion on circulating soluble adhesion molecules in critically ill patients.

OBJECTIVE: To study the influence of long-term volume therapy with different solutions and continuous administration of pentoxifylline on plasma concentrations of circulating adhesion molecules. DESIGN: Prospective, randomized study. SETTING: A surgical intensive care unit (ICU) of a university hospital. PATIENTS: Forty-two patients with sepsis secondary to major surgery were included. INTERVENTIONS: The patients were randomly separated into three groups. In group 1 (n=14), volume therapy was exclusively carried out with 10% low-molecular-weight hydroxyethyl starch solution. In group 2 (n=14), patients exclusively received 20% human albumin for volume therapy. In group 3 (n=14), volume therapy was not defined and pentoxifylline was continuously given (1.4 mg/kg/hr iv). MEASUREMENTS AND MAIN RESULTS: From arterial blood samples, plasma concentrations of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1 [soluble ELAM-1], intercellular adhesion molecule-1 [soluble ICAM-1], vascular cell adhesion molecule-1 [soluble VCAM-1], and soluble granule membrane protein-140) were serially measured on the day of admission to the ICU ("baseline" value) and during the next 5 days at noon. No significant differences between the three groups were found for macrohemodynamics. Soluble ELAM-1, soluble ICAM-1 and soluble VCAM-1 plasma concentrations were markedly higher than normal values at baseline in all groups. In the hydroxyethyl starch group, soluble ELAM-1 plasma concentration decreased to the normal range, whereas it further increased in the human albumin group and was almost unchanged in the pentoxifylline group. During the study period, soluble ICAM-1 and soluble VCAM-1 plasma concentrations remained unchanged in the hydroxyethyl starch group. However, these concentrations increased in the other groups. Soluble granule membrane protein-140 increased significantly only in the human albumin group (483 +/- 103 to 683 +/- 94 ng/mL). In the hydroxyethal starch-treated patients, Acute Physiology and Chronic Health Evaluation II score decreased significantly (from 24.3 +/- 3.4 at baseline to 17.0 +/- 3.3 at the end the study period). Only PaO2/FIO2 was correlated to plasma concentrations of adhesion molecules. CONCLUSIONS: Sepsis is associated with markedly increased plasma concentrations of adhesion molecules, indicating endothelial activation or damage. By long-term volume therapy with hydroxyethal starch solution, these concentrations remained unchanged or even decreased, whereas in patients in whom human albumin was infused or pentoxifylline was given continuously, plasma concentration of soluble adhesion molecules further increased.

Aged↗
PubMed1996

Influence of long-term continuous intravenous administration of pentoxifylline on endothelial-related coagulation in critically ill patients.

OBJECTIVE: To determine the influence of pentoxifylline on endothelial-associated coagulation. DESIGN: Prospective, randomized, placebo-controlled study. SETTING: A surgical intensive care unit of a university hospital. PATIENTS: Consecutive patients (n = 60) with trauma or sepsis secondary to major (nontrauma) surgery. All patients received controlled mechanical ventilation. INTERVENTIONS: According to a randomized sequence, the patients either received pentoxifylline continuously over 5 days (1.5 mg/kg/hr iv) (trauma-pentoxifylline group [n = 15], sepsis-pentoxifylline group [n=15] or saline solution as placebo (trauma-control group [n = 15], sepsis-control group [n = 15]. MEASUREMENTS AND MAIN RESULTS: In addition to the standard coagulation screen, thrombomodulin, protein C, (free) protein S, and thrombin-antithrombin plasma concentrations were measured by enzyme-linked immunosorbent assays. Intensive care therapy, hemodynamics, and changes of Acute Physiology and Chronic Health Evaluation II score were comparable for pentoxifylline-treated and nontreated patients. An average dose of 2.5 g/day of pentoxifylline (range 2.2 to 2.9) was infused into the pentoxifylline-treated patients. At baseline, plasma thrombomodulin concentrations were higher in the septic patients than in the trauma patients. Thrombomodulin plasma concentrations increased significantly more in the control patients (trauma: from 38.9 +/- 10.5 to 59.9 +/- 10.1 ng/mL; sepsis: from 49.7 +/- 12.1 to 72.3 +/- 11.2 ng/mL) than in the pentoxifylline-treated patients (trauma: from 37.9 +/- 11.9 to 50.2 +/- 9.2 ng/mL; sepsis from 51.9 +/- 10.1 to 63.3 +/- 10.2). Starting from similar baseline values, protein C concentration increased significantly more in the sepsis-pentoxifylline patients (from 52.0 +/- 11.1% to 69.1 +/- 11.1%) than in the untreated septic patients (from 50.1 +/- 10.0% to 52.5 +/- 9.5%). There were no significant differences between the pentoxifylline-treated and nontreated groups for protein S and thrombin-antithrombin concentrations. Standard coagulation parameters (fibrinogen, activated partial thromboplastin time, antithrombin III) did not differ between these groups either. CONCLUSIONS: Continuous intravenous administration of pentoxifylline for 5 days beneficially influenced the thrombomodulin/protein C/protein S system in both the trauma and septic patients.

APACHE↗
PubMed1996

The influence of volume therapy and pentoxifylline infusion on circulating adhesion molecules in trauma patients.

Adhesion molecules appear to play a pivotal role in tissue damage secondary to the inflammatory process. Besides neutrophil- and endothelial-bound adhesion molecules, soluble forms have been detected in the circulating blood. They seem to be good markers of endothelial damage, but they may also have other biological functions. Plasma concentrations of soluble adhesion molecules (endothelial leucocyte adhesion molecules (sELAM-1), intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and granule membrane protein 140 (sGMP-140) were serially measured over 5 days by enzyme-linked immunosorbent assays (ELISA) in 45 consecutive trauma patients. These received, by random allocation, only either hydroxyethylstarch solution 10% (mean molecular weight 200,000 daltons) (n = 15) or human albumin 20% (n = 15) for volume therapy. Another 15 patients without defined volume therapy received pentoxifylline continuously (1.2 mg.kg-1.h-1). Measurements were carried out on the day of admission to the intensive care unit (baseline) and during the next 5 days. At baseline, plasma concentrations of all adhesion molecules were similar in all groups. In the hydroxyethyl starch group, sELAM-1 and sICAM-1 concentrations decreased significantly (p < 0.05) reaching normal values during the study period whereas the mean (SD) values increased in the pentoxifylline group (sELAM-1: 71.1 (16.7) to 91.6 (17.8) ng.ml-1) and the albumin group (sICAM-1: 400 (81) to 749 (101) ng.ml-1) (p < 0.05). sVCAM-1 increased outside the normal range only in the human albumin group (to 760 +/- 69 ng.ml-1) (p < 0.05). sGMP-140 plasma concentration increased only in those receiving albumin (432 (85) to 550 (93) ng.ml-1) and this was significantly different to the other groups (p < 0.05). None of the other haemodynamic or laboratory factors could be correlated with plasma concentrations of the adhesion molecules. We conclude that volume therapy with hydroxyethyl starch resulted in a decrease in circulating adhesion molecules in our trauma patients. In contrast, volume therapy with albumin did not exert this effect. Continuous infusion of pentoxifylline did not have a beneficial modulating action on circulating adhesion molecules.

Adult↗
PubMed1996

Can clonidine, enoximone, and enalaprilat help to protect the myocardium against ischaemia in cardiac surgery?

OBJECTIVE: To evaluate whether clonidine, enoximone, and enalaprilat reduce ischaemia-related myocardial cell damage in cardiac surgery. DESIGN: Prospective randomised controlled trial. SETTING: Clinical investigation in a cardiac anaesthesia department of a university hospital. PATIENTS: 88 consecutive patients undergoing coronary artery bypass surgery. INTERVENTIONS: After induction of anaesthesia patients continuously received the alpha 2 agonist clonidine (group 1, n = 22), the phosphodiesterase (PDE) III inhibitor enoximone (group 2, n = 22), the angiotensin converting enzyme (ACE) inhibitor enalaprilat (group 3, n = 22), or saline solution as placebo (control group, n = 22). The infusion was stopped immediately before the start of cardiopulmonary bypass. MAIN OUTCOME MEASURES: The ST segment was analysed and the activity of creatine kinase isoenzyme MB (CKMB), cardiac troponin T (TnT), and the BB isoenzyme of glycogen phosphorylase (GPBB) were measured before the start of infusion (baseline), after weaning from cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB, and on the morning of the first and third postoperative days. RESULTS: Biometric data and time of cross-clamping were not significantly different in the four groups. Changes in the ST segment indicating ischaemia were least common in the enalaprilat group (P < 0.05). Postoperatively, CKMB activity was significantly higher in the clonidine and the control groups. Both new markers of myocardial cell damage increased more after CPB and postoperatively in the control patients (TnT peak: (mean (SD)) 3.99 (0.35) microgram/1; GPBB peak: 82 (15) ng/ml) and the clonidine-treated group (TnT peak: 3.80 (0.3) microgram/1; GPBB peak: 85 (14) ng/ml). Enalaprilat-treated patients showed the smallest overall changes in standard (CKMB) and new serological markers of myocardial ischaemia (TnT peak: 0.71 (0.1) microgram/1; GPBB peak: 44 (14) ng/ml). CONCLUSIONS: In patients treated with enalaprilat before CPB, both new, more sensitive markers of ischaemic myocardial tissue damage increased significantly less than in an untreated control group. Those treated with enoximone also had lower plasma concentration of TnT and GPBB than the control group, whereas clonidine did not reduce the concentration of these markers of myocardial ischaemia. Pharmacological interventions, such as the continuous infusion of the ACE inhibitor enalaprilat, before start of CPB may help to protect the heart against ischaemia/reperfusion injury.

Adrenergic alpha-Agonists↗
PubMed1996

Comparison of different prophylactic myocardium saving measures during heart surgery. Effects on perioperative troponin-T levels.

OBJECTIVE: Different prophylactic myocardium saving strategies are often routine in open heart surgery. Even if theoretically well established, they must be critically reviewed in times of limited financial resources. EXPERIMENTAL DESIGN: Troponin-T (TnT) is a valuable tool to detect even minor myocardial damages independently from concomitant muscle injuries. We measured intra- and postoperative TnT-values and ST-wave deviations on the ECG in a control group and in patients receiving one of the following prophylactic MEASURES: hypothermia during cardiopulmonary bypass (CPB), nitroglycerine ([0.5 microgram/kg/min]) or nifedipine [0.1 microgram/kg/min] after aortic cross-clamping until end of operation, or perioperative Mg2+ per os. PATIENTS AND SETTING: The study included 65 patients of a university hospital with preoperative good heart function scheduled for elective aorto-coronary bypass operation. RESULTS: TnT values increased in all groups after CPB and peaked between end of operation and first post-operative day. TnT values above the critical border of 1.0 microgram/l in the early period after CPB were less often seen in the nitroglycerine and nifedipine group. No pronounced differences could be observed after the first postoperative day. Patients of the hypothermia group had most often TnT values above 1.0 microgram/l. Maximum TnT values of the control, the hypothermia and the Mg(2+)-group correlated with the duration of aortic-crossclamping. No correlation existed between ST-deviations and TnT-values. CONCLUSIONS: The prophylactic measures failed to reduce myocardial damage as evidenced by the course of TnT values. They can therefore not be recommended as routine strategies in patients with good left heart function. Especially hypothermia should be considered carefully.

Aged↗