Coagulation abnormalities in the OR and on the ICU.
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Blood Coagulation Disorders↗
Biomedical subjects
J Boldt
Publications and source records attributed to J Boldt.
Cardiac risk patient--intraoperative contribution: anaesthetic management.
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Anesthesia, Conduction↗
Alterations in circulating vasoactive substances in the critically ill--a comparison between survivors and non-survivors.
OBJECTIVE: Regulation of circulatory homeostasis is based on several factors including various circulating vasoactive substances. Whether these regulators differ between survivors and non-survivors was investigated in critically ill patients. DESIGN: Prospective study. SETTING: Clinical investigation on a surgical intensive care unit of an university hospital. PATIENTS: 60 consecutive patients suffering from trauma (n = 21) or postoperative complications (n = 39) were studied prospectively. The patients were divided into survivors (n = 27) and non-survivors (n = 33). Therapy was adjusted to the standards of modern intensive care management by physicians who were not involved in the study. MEASUREMENTS AND RESULTS: Endothelin-1, atrial natriuretic peptide (ANP), vasopressin, renin, and catecholamine (epinephrine, norepinephrine) plasma levels were measured from arterial blood samples using radioimmunoassay (RIA) or high-pressure liquid chromatography (HPLC) technique on the day of admission to ICU and during the following 5 days. Various hemodynamic parameters were also monitored during that period. The non-survivors showed elevated pulmonary artery pressure (PAP: 34.1 +/- 5.4 mmHg) and pulmonary capillary wedge pressure (PCWP: 20.3 +/- 7.3 mmHg) already at the beginning of the study. Cardiac index (CI) did not differ among the groups, whereas right ventricular ejection fraction (RVEF) decreased in the non-survivors. PaO2/FIO2 decreased only in the non-survivors, whereas VO2 increased in the survivors (from 246 +/- 48 to 331 +/- 43 ml/min). Plasma levels of renin (from 206 +/- 40 to 595 +/- 81 pg/ml) and vasopressin (from 5.78 +/- 0.82 to 7.97 +/- 0.69 pg/ml) increased significantly in the non-survivors. Epinephrine and norepinephrine plasma concentrations were elevated in the non-survivors already at baseline and tremendously increased in these patients during the following days. ANP plasma levels significantly increased also only in the non-survivors (from 188 +/- 63 to 339 +/- 55 pg/ml) (p < 0.05). Endothelin-1 decreased in the survivors, whereas it significantly increased in the non-survivors (from 3.62 +/- 0.68 to 9.37 +/- 0.94 pg/ml) during the study period (p < 0.05). Analyses of co-variance revealed overall no significant correlation between circulating vasoactive substances and hemodynamics. CONCLUSIONS: Systemic and regional regulators of the circulation were markedly changed by critical illness. In survivors, these regulators almost normalized within the study period of 5 days, whereas in non-survivors these alterations were even aggravated. It can only be speculated whether these regulator systems were influenced by activation of various mediator systems or whether they themselves influenced the negative outcome in the non-survivors.
APACHE↗
Thrombomodulin in intensive care patients.
OBJECTIVE: Changes of endothelial-related coagulation was studied in intensive care patients. DESIGN: Descriptive, prospective. SETTING: Clinical investigation, intensive care unit of an university hospital. PATIENTS: 40 consecutive critically ill patients with severe trauma (n = 20) or postoperative complications (n = 20) were studied. 14 patients suffered from sepsis, 12 patients suffered from acute renal failure. INTERVENTIONS: 12 patients with acute renal failure were continuously hemofiltrated. All patients were on continuous sedation (fentanyl and midazolam) and mechanical ventilation. MEASUREMENTS: In addition to standard coagulation variables, thrombomodulin (TM), protein C and protein S as well as thrombin/antithrombin III (TAT) plasma concentrations were measured from arterial blood samples using enzyme-linked immuno-sorbent assays (ELISA). Measurements were carried out on the day of admission (trauma patients) or on the day of diagnosis of sepsis and during the next 4 days. MAIN RESULTS: Throughout the entire investigation period, TM plasma concentrations in patients with sepsis (baseline: 90 +/- 25 micrograms/l, 4th day: 152 +/- 28 micrograms/l) were significantly higher than in non-septic patients (baseline: 60 +/- 29 micrograms/l, 4th day: 42 +/- 15 micrograms/l). 15 of the 40 patients died within or after the end of the investigation period. TM plasma concentrations of survivors were lower (maximum: 63 +/- 18 micrograms/l) than in the non-survivors (maximum: 159 +/- 22 micrograms/l) (p < 0.05). Hemofiltered patients showed higher TM plasma levels, which further increased during the hemofiltration procedure. Protein C and (free) protein S were without significant group differences. TAT plasma levels were elevated above normal in all patients (no group differences). CONCLUSIONS: Besides plasmatic and platelet-related coagulation, endothelium-associated coagulation appears to be also important for maintenance of hemostasis. TM plasma concentrations were elevated in all our critically ill patients, particularly when sepsis was evident. This appears to be most likely due to endothelial membrane damage with increased release of membrane-bound TM into the circulating blood in these patients. The importance of the elevated plasma levels of circulating soluble TM on hemostasis in these patients is an ongoing debate and warrants further studies.
Adult↗
[Anesthesia for heart transplantation in newborn and suckling infants. Special aspects of the hypoplastic left heart syndrome].
Paediatric cardiac transplantation (pHTX) has gained widespread acceptance as a therapy in end-stage myocardial failure and some forms of congenital heart disease, particularly hypoplastic left heart syndrome (HLHS). The major problems to the anaesthesiologist in these patients are induction of anaesthesia in infants with HLHS and treatment of pulmonary hypertension in the early post-bypass period. PATIENTS AND METHODS. Anaesthesia for pHTX was performed in 15 children < 1 year of age (4-237 days); 12 suffered from HLHS, 2 from endocardial fibroelastosis, and 1 from dilatative cardiomyopathy. Induction of anaesthesia in patients with HLHS IS a challenge to the anaesthesiologist, as he has to maintain the delicate balance between pulmonary and systemic blood flow. Anaesthesia was induced with fentanyl (10-15 micrograms/kg) and pancuronium (0.2-0.4 mg/kg) and maintained with fentanyl (total dosage 70-100 micrograms/kg). Modification of ventilatory parameters such as FiO2, PaCO2, and airway pressure (PEEP, I:E ratio) was used to influence systemic and pulmonary blood distribution in the pre-bypass period according to changes in haemodynamics (target: O2 saturation approximately 75%-80%, PaCO2 45-50 mmHg). Treatment of pulmonary hypertension in the weaning and early post-bypass period consisted of respiratory (PaCO2 < 30 mmHg) and metabolic alkalinisation (pH 7.45-7.55, BE > +3 mmol/l), the use of prostaglandin E1 (3-6-12 micrograms/kg.h), and the phosphodiesterase inhibitor enoximone (10-15 micrograms/kg.min). Additional positive inotropic support was achieved with dobutamine (5-10 micrograms/kg.min), adrenaline (0.1-0.5 micrograms/kg.min), and/or orciprenaline (0.1-0.2 micrograms/kg.min) and calcium chloride (25-100 mg/kg). RESULTS. Two children died intraoperatively and 1 on the 1st postoperative day from overwhelming pulmonary vascular resistance and right ventricular failure. Three children died between 3 and 4 weeks postoperatively, 1 from cytomegalovirus infection, 1 from sepsis, and 1 from acute rejection. Nine patients survived and are well up to 5.5 years after transplantation. CONCLUSION. Pulmonary hypertension in the weaning and early post-bypass period is the main anaesthesiological problem of pHTX, particularly in children with HLHS. A polypragmatic approach to this problem consisting of alkalinisation, pulmonary vasodilatation, and inotropic support is presented and seems to be effective. Further improvements in concepts of pHTX are limited by the lack of donor organs. Though the experience with pHTX in neonates and infants is growing slowly, it might be a routine procedure from the anaesthesiological point of view within a few years in some selected centres.
Anesthesia↗
[Continuous monitoring of critical patients with a newly developed pulmonary arterial catheter. A cost analysis].
The introduction of flow-directed pulmonary artery (PA) catheters has helped to improve our knowledge of cardiovascular physiology. There have been several developments of this equipment in recent years, including continuous monitoring of mixed-venous O2 saturation (SvO2) and cardiac output (CO). The high purchase price, however, is an obstacle to its use in the critically ill. The aim of the present study was to analyse the actual costs of these devices in comparison to standardly used intermittent monitoring of SvO2 and CO. METHODS. Thirty critically ill patients in a surgical intensive care unit (ICU) were prospectively studied. PA catheter monitoring was indicated by physicians who were not involved in the study. The patients were randomly allocated to one of the following groups: 1. a standard PA catheter was used, and SvO2 and CO were intermittently measured 6 times a day on a routine basis and additionally when necessary from the clinical point of view; 2. SvO2 was continuously measured using a fiberoptic PA catheter; and 3. CO was continuously monitored using a newly developed PA catheter. Costs for the catheter equipment and laboratory analyses (SvO2) were calculated and the durations of intermittent monitoring techniques were measured. Costs for the 'hardware' (monitor, blood gas analyser) were not taken into account. SvO2 was measured by the ICU staff using an ICU-owned blood gas analyser (4.78 DM/analysis) and by a central laboratory unit, which had to be paid for its analyses (30.50 DM/analysis), respectively. RESULTS. The groups were comparable with regard to their demographic data. A total of 378 intermittent measurements of SvO2 and 449 mean CO measurements (1611 single bolus CO measurements) were carried out in the patients in whom a standard PA catheter was inserted. For daily calibration, a total of 50 single SvO2 measurements were done in the group in which SvO2 was continuously monitored. A total of 27.7 h were spent for intermittent SvO2 measurements (time range of one analysis using the ICU-based blood gas analyser: 4.0 to 7.9 min); intermittent CO monitoring took a total of 14.2 h (time range of one mean CO measurement: 1.6 to 3.0 min). When blood gases were analysed by a central laboratory unit, costs for intermittent SvO2 were tremendously higher than when monitored continuously. CONCLUSION. Monitoring devices that provide us with continuous information on the patient's state may have advantages in the management of the critically ill. Whether the patient's 'outcome' can be improved by monitoring SvO2 and CO continuously was not addressed by the present study. Instead, this study focused on the question of whether these devices are more cost-intensive than standard PA catheter monitoring systems. Costs for laboratory analyses can blunt the advantage of lower costs for the standard PA catheter. Intermittent (standard) monitoring of SvO2 and CO was significantly more time-consuming than the continuous methods. It can be summarised that although purchase costs for the more advanced PA catheters are higher than for standard PA catheters, the use of these continuous monitoring devices in the critically ill can be justified from a financial point of view.
Cardiac Output↗
[Tamm-Horsfall protein, alpha-1- and beta-2-microglobulin as kidney function markers in heart surgery].
After cardiac surgery, transient renal dysfunction often occurs. Regional differentiation of these processes is possible only using invasive techniques, including renal biopsy. Approximately 30 different plasma protein components have been identified in the urine of healthy individuals by means of qualitative and quantitative immunochemical methods. The detection of microalbuminuria has high diagnostic relevance for the early diagnosis of renal damage at a reversible stage. One typical urinary protein is Tamm-Horsfall protein (THp). After histochemical staining of human kidney sections, activity is seen in the loop of Henle and initial distal tubule. The assay of alpha-1 microglobulin (MG) in urine is considered one of the most efficient laboratory parameters for the diagnosis of tubular lesions. Serum concentrations of alpha-1 MG are less dependent on extrarenal changes than are those of other low-molecular-weight proteins. beta-2 MG is also one of the standards used in recent years for diagnostic relevance. Urinary albumin excretion, normally less than 30 mg per day, sometimes increases after glomerular damage. Some renal function tests are used daily in many intensive care units, e.g. creatinine clearance (CCr) or urea and sodium excretion. Renal dysfunction should, however, be further examined to localise regional damage and to seek new clinical standards in addition to the conventional tests. METHODS. After obtaining the agreement of the local ethics committee, 30 patients were divided into two groups of 15 each: group I without renal dysfunction and CCr more than 60 ml/min; and group II with CCr below 60 ml/min. THp and alpha-1 MG were measured pre- and postoperatively after open heart surgery with the ELISA and beta-2 MG with the nephelometric technique. These parameters were compared with clinical standards such as albumin excretion, blood urea nitrogen (BUN), urea clearance, and fractional sodium excretion. RESULTS. The CCr did not change in group I from the pre- to postoperative period (81.5 to 85.1 and 91.4 ml/min), nor did excretion of THp (20.1 to 25.0 and 24.8 mg/day), correlation r = 0.7; P < 0.001). The elimination of alpha-1 and beta-2 MG was significantly higher in the postoperative period in this group (alpha-1: 7.2 to 44.1 and 100.6 mg/day; beta-2: 0.3 to 2.1 and 3.2 mg/day). In group II CCr showed pathological values (36.8 to 31.1 and 36.3 ml/min), as did simultaneous THp (13.5 to 9.7 and 12.7 mg/day). alpha-1 and beta-2 MG values became more pathological in the postoperative period than in group I (alpha-1: 32.8 to 113.9 and 198.5 mg/day; beta-2: 0.7 to 5.8 and 16.9 mg/day). DISCUSSION. Measurement of the excretion of THp and alpha-1 and beta-2 MG is a useful addition to present clinical standards for recognising early changes in renal function. The increases in the postoperative period after cardiac surgery showed tubular damage even in patients without predictive risk factors or clinical signs. In patients with renal dysfunction open heart surgery and extracorporeal circulation led to significant tubular damage.
Aged↗
Circulating adhesion molecules in cardiac operations: influence of high-dose aprotinin.
Cardiac operations using cardiopulmonary bypass (CPB) are associated with a systemic inflammatory response most likely attributable to the release of various inflammatory mediators and activation of complement or coagulation cascade. In addition, (circulating) adhesion molecules, such as endothelial leukocyte adhesion molecule (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1), appear to be of central importance in the CPB-related inflammatory process. In this situation, antiproteases, such as aprotinin, may help to prevent damage of endothelial integrity. In a prospective study, 40 consecutive patients undergoing elective cardiac operation were randomly divided into two groups (with 20 patients in each group): in group 1 "high-dose" aprotinin was used (2 million IU of aprotinin before CPB, 500,000 IU/h until end of operation, 2 million IU added to the prime) (with aprotinin), and in group 2 no aprotinin was given (without aprotinin). Circulating adhesion molecules (cICAM-1, cELAM-1, and cVCAM-1) were measured from arterial blood samples using ELISA after induction of anesthesia (baseline), during CPB, at the end of the operation, 5 hours after CPB, and on the first postoperative day. The two groups were comparable concerning their biometric profile and CPB data. Baseline values of circulating adhesion molecules were within normal range and similar in both groups. During CPB, hemodilution resulted in a decrease in all circulating adhesion molecules. On the first postoperative day, cICAM-1 (with aprotinin, 215 +/- 32 ng/mL; without aprotinin, 230 +/- 40 ng/mL) and cELAM-1 (with aprotinin, 28 +/- 6 ng/mL; without aprotinin, 31 +/- 6 ng/mL) returned to baseline values.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Analysis of TEST (TES and Tris) yolk buffer effects on human sperm.
OBJECTIVE: To assess different parameters of TEST (TES and Tris) yolk buffer (TYB) treatment of human sperm that may contribute to the biologic effects of TYB on sperm function. DESIGN: The influence of TYB treatment on occurrence of acrosome reactions was studied, as was the influence of the concentration of acrosome-reacted sperm reacted by TYB or Biggers-Whitten-Whittingham medium (BWW) incubation on penetration levels in the sperm penetration assay (SPA). The necessity for the TYB to achieve enhanced SPA performance as well as the effect of heat shock on sperm also were studied. SETTING: Andrology laboratory of a university hospital. PATIENTS: Sperm donors. MAIN OUTCOME MEASURES: Sperm penetration levels in the SPA and acrosomal loss as evaluated by a fluorescent lectin staining technique. RESULTS: Sperm incubated in TYB for 42 to 46 hours at 4 degrees C demonstrated a higher rate of acrosomal loss than did sperm capacitated in BWW media for 20 to 22 hours. The difference was not significant. When insemination concentrations were normalized to identical concentrations of acrosome-reacted sperm, TYB treated specimens demonstrated much higher penetration levels compared with BWW specimens. Samples incubated in BWW versus TYB for 42 to 46 hours at 4 degrees C before heat shock had identical penetration levels. Samples washed with 37 degrees C BWW (positive heat shock) had significantly higher penetration levels than did samples washed with 4 degrees C BWW (negative heat shock). CONCLUSION: Although TYB treatment does increase the occurrence of acrosome reactions, this alone does not account for the dramatic increase in penetration levels in SPA seen with these samples. TEST yolk buffer is not required for enhancement of penetration, and the heat shock step of the procedure seems to be most important for enhancement of sperm fusion ability in the SPA.
Acrosome↗
RETRACTED: Cardiorespiratory response of intravenous angiotensin-converting enzyme inhibitor enalaprilat in hypertensive cardiac surgery patients.
Twenty-four patients undergoing elective coronary artery bypass surgery were studied. Either the angiotensin-converting enzyme (ACE) inhibitor enalaprilat, 0.06 mg/kg, (n = 12), or saline solution (= control group; n = 12), was randomly and blindly administered intravenously when the mean arterial blood pressure (MAP) increased to 90 mmHg after induction of anesthesia. Cardiorespiratory parameters were studied before injection, during the subsequent 30 minutes, precardiopulmonary bypass (CPB), post-CPB, and at the end of surgery. MAP was significantly reduced 5 minutes after administration of enalaprilat. The peak reduction of blood pressure was observed after 30 minutes (from 98 +/- 4 to 68 +/- 8 mmHg). Even immediately before CPB (112 +/- 12 minutes after injection of enalaprilat), MAP and systemic vascular resistance were significantly lower than baseline values. Heart rate remained almost unchanged in both groups. Cardiac index increased slightly in the enalaprilat patients (maximum: +0.75 L/min/m2 20 minutes after injection). Filling pressures (central venous pressure, pulmonary capillary wedge pressure) were also significantly reduced by enalaprilat. There were no differences from the control patients with regard to changes in right ventricular hemodynamics (right ventricular ejection fraction, right ventricular end-diastolic volume, right ventricular end-systolic volume), pulmonary gas exchange (PaO2), or intrapulmonary right-to-left shunting (Qs/Qt). VO2 increased only in the enalaprilat patients (from 179 +/- 28 to 230 +/- 30 mL/min) (p < 0.05). Cardiorespiratory parameters did not differ between the two groups post-CPB.(ABSTRACT TRUNCATED AT 250 WORDS)
Blood Pressure↗
Endothelial-related coagulation in cardiac surgery.
The endothelium appears to play an important role in the regulation of intravascular coagulation. Thrombomodulin is one of the anticoagulant substances that is expressed by endothelial cells. The influence of age and illness on the thrombomodulin-protein C system was studied prospectively in 80 cardiac surgery patients. Patients > 70 yr old (n = 20) were compared with patients < 50 yr (n = 20) (group I), and patients undergoing a simple cardiac procedure (n = 20) were compared with patients scheduled for complex surgery (n = 20) (group II). Thrombomodulin (normal < 40 ng ml-1), protein C and (free) protein S plasma concentrations were measured by enzyme-linked immunosorbent assays (ELISA) after induction of anaesthesia (baseline values), during and after cardiopulmonary bypass (CPB), at the end of surgery, 5 h after CPB and on the first day after operation. Blood loss and use of homologous blood and blood products were significantly greater in patients > 70 yr and in those undergoing complex surgery. At baseline, thrombomodulin concentration was increased in patients undergoing complex surgery (mean 52 (sd 9) ng ml-1). After bypass and after operation, thrombomodulin increased most in patients > 70 yr (from 40 (8) to 78 (10) ng ml-1) and in those patients who underwent complex cardiac operations (from 52 (8) to 79 (10 ng ml-1) (P < 0.05). Changes in protein C and protein S concentrations were similar in all groups. On the first day after operation only, protein C concentrations were reduced in patients > 70 yr and in patients who underwent complex cardiac surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Does the type of volume therapy influence endothelial-related coagulation in the critically ill?
The endothelium plays an important role in the regulation of haemostasis by producing substances such as thrombomodulin (TM). The influence of long-term volume replacement with different types of fluid on the TM-protein C-protein S system was investigated in a prospective, randomized study. Thirty trauma patients and 30 patients suffering from sepsis after major surgery received either 10% low-molecular weight (LMW) hydroxyethylstarch solution (HES-trauma, n = 15; HES-sepsis, n = 15) or 20% human albumin (HA-trauma, n = 15; HA-sepsis, n = 15) for 5 days to maintain central venous pressure (CVP) between 12 and 16 mm Hg. Plasma concentrations of TM, protein C, (free) protein S and thrombin-antithrombin (TAT) were measured in arterial blood samples obtained on the day of admission to the intensive care unit or on the day of diagnosis of sepsis and over the next 5 days. There were no differences between HA- and HES-treated trauma patients. Protein C and protein S also did not differ between HA- and HES-treatments. At baseline, TM plasma concentrations were increased to > 40 micrograms litre-1 in both sepsis groups only. In the HA-sepsis group, TM increased significantly (from 48.1 (SD 13.9) to 68.4 (13.0) micrograms litre-1), whereas it remained almost unchanged in the HES-sepsis group. In HES-sepsis patients, protein C (from 51.0 (10.1) to 71.9 (8.9)%) and protein S (from 19.0 (6.0) to 40.8 (11.4)%) increased significantly during the study, whereas both remained reduced in HA-patients. TAT (indicating intravascular coagulation) did not differ between the two fluid groups. We conclude that in trauma patients, the type of volume therapy had no influence on the TM-protein C-protein S system. In sepsis patients, volume therapy with HES was beneficial, whereas infusion of HA had no substantial positive effect on endothelial-associated coagulation.
Adult↗
Influence of intravenous administration of angiotensin-converting enzyme inhibitor enalaprilat on cardiovascular mediators in cardiac surgery patients.
The renin-angiotensin system (RAS) is important in controlling and maintaining cardiovascular homeostasis. In a randomized, prospective study, the response to intravenous (i.v.) administration of the angiotensin-converting enzyme (ACE) inhibitor enalaprilat (0.06 mg/kg) on important controllers of the circulation was investigated in 14 patients undergoing aortocoronary bypass grafting with a mean arterial blood pressure (MAP) > 85 mm Hg after induction of anesthesia. Fourteen patients received saline solution as placebo (control group). Endothelin (ET), atrial natriuretic peptide (ANP), catecholamine (epinephrine, norepinephrine) plasma levels, and ACE activity were measured from arterial blood sampled before injection of enalaprilat or NaCl solution (baseline values), 10 min and 30 min thereafter, immediately before the start of cardiopulmonary bypass (CPB), immediately after CPB, and at the end of surgery. MAP, heart rate (HR), cardiac index (CI), and systemic vascular resistance (SVR) were also monitored. ACE activity was similar at baseline in both groups; after i.v. injection of enalaprilat, it significantly decreased (from 35.1 +/- 11 to 4.4 +/- 1.0 U.min-1.L-1 30 min after injection) and remained reduced until the end of the operation (295 +/- 31 min after injection). ANP plasma levels were increased beyond normal (> 100 pg/mL) at baseline in both groups. They increased significantly in the control patients, but remained almost unchanged in the enalaprilat-treated patients within the entire study period. Plasma concentration of ET also increased only in the control group and was increased after CPB (8.6 +/- 1.2 pg/mL at the end of the operation).(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Circulating adhesion molecules in pediatric cardiac surgery.
Cardiopulmonary bypass (CPB) may be associated with the risk of a "whole body inflammation." Adhesion molecules, such as endothelial leukocyte adhesion molecule (ELAM-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), seem to play a pivotal role in the inflammatory response. Soluble forms of these adhesion molecules may serve as markers of endothelial activation or damage. To elucidate whether plasma levels of soluble adhesion molecules differ between pediatric and adult cardiac surgery patients, 15 consecutive children younger than 5 yr undergoing CPB were prospectively studied and compared with adults scheduled for elective coronary artery bypass grafting and valve replacement. Plasma levels of circulating (soluble) adhesion molecules (sELAM-1, sICAM-1, sVCAM-1) were measured from arterial blood samples using enzyme-linked immunosorbent assays after induction of anesthesia (= "baseline"), during CPB, at the end of surgery, and on postoperative days 1 and 2. At baseline, plasma levels of all three soluble adhesion molecules were significantly higher in children than in adults. sELAM-1 and sICAM-1 plasma concentrations were even beyond normal in the children (sELAM-1: 88.8 +/- 13.8 ng/mL; sICAM-1: 349 +/- 27 ng/mL). During CPB and until the end of surgery, plasma levels of all adhesion molecules decreased in the children and remained almost unchanged in the adults. In the children, sELAM-1 remained lower than baseline values until the second postoperative day (45.2 +/- 12.2 ng/mL), whereas sICAM-1 increased in the postbypass period without, however, reaching baseline values (254 +/- 40 ng/mL).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Beta 2-adrenoceptor density of human lymphocytes after nitroprusside-induced hypotension.
The present study was undertaken to assess the influence of nitroprusside-induced hypotension on beta 2-adrenoceptor density. Twenty-four patients undergoing nose-septum corrections under general anesthesia were allocated randomly to a nitroprusside or control group. beta 2-Receptor density on lymphocytes was measured by binding studies using (-)125-iodocyanopindolol. Lymphocyte subpopulations B, T, Thelper, Tsuppressor, and natural killer cells were determined simultaneously by flow cytometry. Five of 12 nitroprusside-treated patients developed significant intraoperative increases of epinephrine levels (+69% versus preoperatively) which were not seen in the remaining seven patients. In these five patients, beta 2-receptor density of unfractionated lymphocytes was 26% lower (P < 0.05) on the first day after surgery compared with preoperative values. Since no changes in proportions of lymphocyte subpopulations were observed, these results are not caused by redistribution phenomena inducing a decrease of subsets with a high number of beta receptors. These findings suggest that beta 2-adrenergic responsiveness might be diminished after nitroprusside treatment in some patients.
Adrenergic beta-Antagonists↗
Continuous i.v. administration of the angiotensin-converting enzyme inhibitor enalaprilat in the critically ill: effects on regulators of circulatory homeostasis.
Several components are responsible for circulatory control at the central, regional, and microcirculatory level. Angiotensin-converting enzyme (ACE) inhibitors are known to act beneficially on circulation by various mechanisms. The influence of continuous i.v. administration of the ACE inhibitor enalaprilat on regulators of circulation was studied in 45 critically ill patients. According to a prospective randomized sequence, either 0.25 mg/h (group 1, n = 15) or 0.5 mg/h (group 2, n = 15) of enalaprilat or saline solution as placebo (control group, n = 15) were continuously given. Infusion was started on the day of admission to the intensive care unit (ICU) and continued for the next 5 days. From arterial blood samples, plasma levels of endothelin-1 (ET), atrial natriuretic peptide (ANP), renin, vasopressin, angiotensin-II, and catecholamines (epinephrine, norepinephrine) were measured. All measurements were carried out before infusion (= baseline values) and during the next 5 days. In both enalaprilat groups, mean arterial blood pressure (MAP) decreased similarly; heart rate (HR) and central venous pressure (CVP) did not change, and were without differences in comparison to the untreated control. Except for ET, plasma levels of all vasoactive substances exceeded normal range at baseline. Angiotensin-II plasma concentrations significantly decreased during enalaprilat infusion (0.25 mg/h: from 53.1 +/- 11.3 to 22.1 +/- 9.3 pg/ml; 0.50 mg/h: 62.1 +/- 14.4 to 17.9 +/- 7.9 pg/ml), but they remained significantly elevated in the untreated control patients. Vasopressin plasma level increased only in the control group (p < 0.01) and decreased in the patients in whom 0.50 mg/h of enalaprilat was infused.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The effect of the anticoagulation regimen on endothelial-related coagulation in cardiac surgery patients.
Heparin is still the most commonly used anticoagulant in cardiac surgery necessitating cardiopulmonary bypass. In recent years, endothelial-related coagulation (e.g. thrombomodulin/protein C-system) has enlarged our knowledge of the regulation of haemostasis. In a controlled randomised study, the influence of different regimens of anticoagulation on the thrombomodulin/protein C-system was studied. Sixty patients undergoing elective coronary artery bypass grafting were randomly allocated into four groups (n = 15) to receive: 300 IU.kg-1 of heparin before bypass; 600 IU.kg-1 of heparin; 300 IU.kg-1 of heparin as bolus followed by a continuous infusion of 10 000 IU.h-1 until the end of bypass; or 600 IU.kg-1 of heparin plus 'high dose' aprotinin (2 million IU of aprotinin before bypass, 500 000 IU.h-1 until the end of the operation and 2 million IU added to the bypass pump prime). Grouping was blinded for the surgeon and the anaesthetist. Plasma concentrations of thrombomodulin, protein C and (free) protein S as well as thrombin/antithrombin III were measured by enzyme-linked-immunosorbent assays after induction of anaesthesia, during and after bypass, at the end of surgery, 5 h after bypass, and on the first postoperative day. Activated clotting time was significantly longer during bypass in group 2 (566 (60)s) and group 4 (655 (59)s), whereas standard coagulation parameters showed no differences between the four groups. Blood loss and use of homologous blood and blood products were highest in groups 2 and 3. Thrombomodulin plasma levels were similar (and normal) at baseline (< 40 ng.l-1), decreased during bypass and reached baseline values postoperatively without showing significant group differences. Protein C did not show any differences among the groups within the investigation period. 'Free' protein S plasma levels were most reduced in group 1 (from 68 (8)% to 48 (9)% after bypass). Thrombin/antithrombin III plasma concentrations increased most in groups 1 (to 69 (14) micrograms.l-1 after bypass) and 2 (to 48 (7) micrograms.l-1 after bypass), whereas they remained significantly lower in groups 3 and 4. The thrombomodulin/protein C-system was not significantly influenced by the regimen of anticoagulation. Administration of 'high-dose' heparin was associated with the highest blood loss, which could not be related to endothelial-associated coagulation.
Aged↗
Cardiorespiratory effects of continuous i.v. administration of the ACE inhibitor enalaprilat in the critically ill.
1. Cardiorespiratory effects of long-term, continuous i.v. administration of the ACE inhibitor enalaprilat were studied. 2. Forty-five consecutive critically patients suffering from trauma or postoperative complications were randomly separated into three groups (15 patients in each group) receiving either 0.25 mg h-1 or 0.50 mg h-1 enalaprilat, respectively, or saline solution as placebo (= control group). The infusion was continued for 5 days. 3. Haemodynamic and respiratory parameters were intensively monitored on admission to the intensive care unit (= 'baseline' values) and daily during the next 5 days. 4. Mean arterial blood pressure (MAP) decreased significantly only in the enalaprilat-treated patients, whereas heart rate (HR) remained unchanged in these patients. 5. Pulmonary capillary wedge pressure (PCWP) and pulmonary artery pressure (PAP) were decreased by enalaprilat (0.50 mg h-1: PAP (mean +/- s.d.) decreased from 28.0 +/- 4.1 to 24.0 +/- 3.0 mm Hg) and remained significantly lower than in the control group. In the untreated control group, cardiac index (CI), oxygen consumption (VO2I) and oxygen delivery (DO2I) significantly decreased, which was blunted by enalaprilat infusion. Oxygen extraction (O2-extr) increased in both enalaprilat groups (0.25 mg h-1: from 26.1 +/- 5.5 to 30.4 +/- 4.0%; 0.50 mg h-1: 25.2 +/- 5.6 to 30.9 +/- 4.4%) and decreased in the control patients. 6. Right ventricular haemodynamics improved by enalaprilat infusion (0.50 mg h-1: RVEF increased from 40.0 +/- 3.5 to 45.5 +/- 4.0%). Lactate plasma concentrations decreased in the group with 0.50 mg h-1 enalaprilat (from 1.9 +/- 1.0 to 1.3 +/- 0.3 mg dl-1) and increased in the control patients. 7. Continuous infusion of the ACE inhibitor enalaprilat exerted beneficial cardiorespiratory effects in the critically ill. The widespread common risk of altered perfusion with decreased CI, DO2, VO2, O2-extr and increased lactate concentration was blunted by enalaprilat infusion. 8. Although 0.5 mg h-1 enalaprilat was most effective, a dose of 0.25 mg h-1 also showed beneficial haemodynamic effects in the critically ill.
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