Biomedical subjects

M Heesen

Publications and source records attributed to M Heesen.

At least 37 records · Page 2Linked to original sources

PubMed1997

Does age influence circulating adhesion molecules in the critically ill?

OBJECTIVE: Soluble adhesion molecules are regarded to be markers of inflammation, endothelial activation, or damage. The influence of age on plasma concentrations of circulating adhesion molecules should be serially studied in critically ill intensive care patients. DESIGN: Prospective and descriptive study over 5 days. SETTING: Clinical investigation in a surgical intensive care unit of a university hospital. PATIENTS: Thirty critically ill patients (Acute Physiology and Chronic Health Evaluation [APACHE] II score of > 15 points), with sepsis secondary to postoperative complications, were included in this study. Fifteen consecutive patients aged < 50 yrs and 15 consecutive patients aged > 70 yrs were prospectively studied. INTERVENTIONS: All patients were treated by the standard protocols of our intensive care unit, which did not differ between the groups. The patients received continuous analgesia-sedation and mechanical ventilation. Intensivists caring for the patients were not involved in the study and were blinded to data analysis. MEASUREMENTS AND MAIN RESULTS: Hemodynamic parameters were extensively monitored in all patients. From arterial blood samples, plasma concentrations of soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, granule membrane protein-140) were measured on the day of admission (i.e., baseline values) and during the following 5 days. Three of the younger patients and six of the elderly patients died during the study period (p < .05). Oxygen delivery and consumption, and the other hemodynamic data, were without group differences throughout the study. Plasma concentrations of all adhesion molecules were beyond normal at baseline in both groups. These concentrations increased further during the first 2 to 3 days in both groups, with a significantly higher increase in the elderly patients (endothelial leukocyte adhesion molecule-1 to 179 +/- 32 ng/mL; intercellular adhesion molecule-1 to 1695 +/- 158 ng/mL; vascular cell adhesion molecule-1 to 1395 +/- 212 ng/mL; and granule membrane protein-140 to 888 +/- 119 ng/mL). In the younger patients, concentrations of soluble adhesion molecules decreased later in the study and almost reached baseline values on day 5. In the elderly patients, these concentrations remained significantly higher until the end of the study. CONCLUSIONS: The higher plasma concentrations of the measured adhesion molecules in elderly critically ill patients indicate that elderly patients are more prone than younger patients to a more pronounced activation or even damage of the endothelium. Further work needs to be done to determine the prognostic importance and to define the role of soluble adhesion molecules, particularly in the elderly critically ill patient.

Adult↗

PubMed1996

Cloning of the mouse fusin gene, homologue to a human HIV-1 co-factor.

Previous studies have demonstrated that mouse cells do not become infected with HIV-1 despite transfection with human CD4. Recently, a human protein termed "fusin" with characteristics of a seven-transmembrane-spanning receptor was found to be a co-factor required for the entry and fusion of HIV-1 with human CD4-bearing lymphocytes. Thus, cloning of the murine homologue of the human fusin (also termed CXCR-4) gene could provide an important comparative tool for identification of the structures crucial for fusin function. Using degenerate PCR, the mouse homologue of human fusin was cloned from a peritoneal exudate cell cDNA library. The predicted amino acid sequence is 91% identical to human fusin. Twenty-eight of the 37 amino acid differences between mouse and human fusin are located in the ectodomains, suggesting that the intracytoplasmic components that mediate G protein binding and signaling are highly conserved. Northern blot analysis showed a message of 2.2 kb in thymus, spleen, neutrophils, and primary astrocyte cultures. Lymphoid and monocyte cell lines also expressed message for fusin. The coding regions of most chemokine receptors lack introns. In contrast, cloning of genomic DNA for mouse fusin revealed the presence of a 2.3-Kb intron separating the first seven amino acids from the remaining 352 residues. Therefore, the mouse fusin gene has a unique genomic organization compared with other chemokine receptors.

Amino Acid Sequence↗

PubMed1996

Mouse astrocytes respond to the chemokines MCP-1 and KC, but reverse transcriptase-polymerase chain reaction does not detect mRNA for the KC or new MCP-1 receptor.

Previous studies demonstrated the involvement of astrocytes in the development of astrogliosis, a condition in which these cells undergo proliferation and hypertrophy. To examine whether astrocytes could migrate into lesions, we tested the influence of the murine chemokines MCP-1, KC, TCA3, and MIP-1 beta on migration of cultured neonatal mouse astrocytes. Subnanomolar concentrations of MCP-1 and KC were active chemoattractants indicating that these molecules were effective at physiologic concentrations. Specificity of MCP-1 was demonstrated by antibody inhibition and by the finding that the chemokine MIP-1 beta failed to induce astrocyte migration. The migratory responses were sensitive to pertussis toxin; this finding is consistent with involvement of G protein-coupled receptors. To examine the receptors for these chemokines further, we cloned the mouse homolog of the human MCP-1 receptor from a mouse peritoneal exudate cell cDNA library. The gene had 78% nucleotide sequence homology with the human MCP-1 receptor (the nucleotide sequence of clone 1 encoding the mouse MCP-1 receptor can be obtained from the GenBank database, accession number U56819). However, reverse transcriptase-polymerase chain reaction (RT-PCR) failed to detect message for either the MCP-1 or KC receptors in astrocytes. The combined data suggest that mouse astrocytes use novel receptors to recognize these chemokines.

Animals↗

PubMed1996

Increase of interleukin-6 plasma levels after elective craniotomy: influence of interleukin-10 and catecholamines.

Accidental and operative trauma are able to induce a systemic reaction of the organism characterized by fever, leukocytosis, catabolism, and an activation of the coagulation system. Interleukin-6 (IL-6) has been found to be an important mediator of this acute-phase response. In this study the influence of elective craniotomy on IL-6 plasma levels was evaluated. Blood samples were obtained from 20 patients undergoing elective craniotomy for vascular or tumorous diseases of the brain. IL-6 increased significantly (p < 0.05) from the pre-operative (0(0-5.4) pg/ml) to the intraoperative (180 min after beginning of surgery) time-point (10.6 (0-18.5) pg/ml). The maximum was reached on the first postoperative morning (13.9(4.3-45.0) pg/ml). Interleukin-10 (IL-10) is an anti-inflammatory cytokine which suppresses IL-6 synthesis in vitro in various cell lines. IL-10 plasma concentrations showed no alterations throughout the study period. Epinephrine plasma concentrations increased significantly from pre-operative values (15 (0-74) pg/ml) to the postoperative time-point (57(9-459) pg/ml). A 4.5-fold increase (p < 0.05) of norepinephrine plasma concentrations was found when comparing the data obtained 60 min after beginning of surgery with the data of the first postoperative morning. In monocytes, which are a major source of plasma IL-6, an elevation of intracellular cAMP stimulates the IL-6 synthesis. The postoperative maximum of IL-6 in plasma could be due to a release of catecholamines. In conclusion this study demonstrated an elevation of IL-6 plasma concentrations during and after elective craniotomy. Increased plasma catecholamine concentrations as well as a damage in the blood-brain barrier due to the surgical trauma with a spill-over of IL-6 from brain tissue into plasma could have contributed to this result.

Acute-Phase Reaction↗

PubMed1996

Influence of different volume therapies on platelet function in the critically ill.

OBJECTIVE: Both albumin and synthetic colloids such as hydroxyethyl starch (HES) solution are used to optimize hemodynamics in the critically ill. The influence of different long-term infusion regimes on platelet function was studied. DESIGN: Prospective, randomized study. SETTING: Clinical investigation on a university hospital surgical intensive care unit. PATIENTS: Twenty-eight consecutive trauma patients (injury severity score > 15 points) and 28 consecutive nontraumatized surgical patients with sepsis. INTERVENTIONS: The patients received either 20% human albumin (HA trauma, n = 14; HA sepsis, n = 14) or 10% low-molecular-weight HES solution HES 200/0.5 (HES trauma, n = 14; HES sepsis; n = 14) for 5 days to maintain central venous pressure and/or pulmonary capillary wedge pressure between 12 and 16 mmHg. MEASUREMENTS AND RESULTS: Platelet function was assessed by aggregometry (= turbidimetric technique) using adenosine diphosphate 2.0 mumol/l, collagen 4 microliters/ml, and epinephrine 25 mumol/l as inductors. Arterial blood was sampled on the day of admission or the day of diagnosis of sepsis (= baseline value) and over the next 5 days. Standard coagulation parameters (antithrombin III, fibrinogen, partial thromboplastin time) were also measured. Total use of HES by the 5th day totalled 4870 +/- 990 ml in the trauma and 3260 +/- 790 ml in the sepsis patients (HA trauma: 1850 +/- 380 ml; HA sepsis: 1790 +/- 400 ml). Maximum platelet aggregation decreased significantly during the first 2-3 days after baseline in all groups. At the end of the investigation period, platelet aggregation variables had recovered and reached (or even exceeded) baseline values. Within the entire investigation period, the course of platelet aggregation variables did not differ significantly between HA and HES-treated patients irrespective of whether they were trauma or sepsis patients. CONCLUSIONS: Alterations in hemostasis may occur for several reasons in the critically ill. Human albumin is the preferred first-line volume therapy in patients at risk for coagulation disorders. With respect to platelet function, volume replacement with (lower-priced) low-molecular-weight HES solutions can be recommended in this situation without any risk.

Adult↗

PubMed1996

The effects of pentoxifylline on circulating adhesion molecules in critically ill patients with acute renal failure treated by continuous veno-venous hemofiltration.

OBJECTIVE: Circulating adhesion molecules appear to be excellent markers of endothelial activation in critically ill patients. Pentoxifylline (PTX) may limit sequelae of inflammation and subsequent endothelial activation by various mechanisms. The influence of PTX on the plasma levels of soluble adhesion molecules in critically ill patients undergoing continuous veno-venous hemofiltration (CVVH) was studied. DESIGN: Prospective, randomized, blinded study. SETTING: Clinical investigation in the surgical intensive care unit of a university hospital. PATIENTS AND PARTICIPANTS: Fourteen consecutive patients suffering from acute renal failure (ARF) with postoperative complications who received continuous pentoxifylline (CVVH-PTX) i.v. were compared with 14 patients with ARF who did not receive PTX (CVVH control group). INTERVENTIONS: Pump-driven CVVH was carried out with a blood flow ranging from 120 to 150 ml/min. All patients received fentanyl and midazolam continuously and were on mechanical ventilation. PTX (300 mg) was given as a loading dose, followed by continuous infusion of 1.2 mg/kg per h for the next 5 days. MEASUREMENTS AND RESULTS: From arterial blood samples, plasma levels of soluble adhesion molecules (endothelial leukocyte adhesion molecules [sELAM-1], and intercellular adhesion molecule-1 [sICAM-1], vascular cell adhesion molecule-1 [sVCAM-1], and P-selectin granule membrane protein [sGMP-140] were measured using enzyme-linked immuno-sorbent assays (ELISA). Measurements were carried out before the start of CVVH to establish baseline values and continued during the next 5 days. MAIN RESULTS: Eleven of the CVVH-PTX patients and 8 of the CVVH control patients survived during the investigation period. In the CVVH-PTX patients 2.4 +/- 0.3 g/day of PTX was given. At baseline, plasma levels of sELAM-1, sICAM-1, and sVCAM-1 were markedly higher than normal in both groups. In the CVVH control patients, all measured soluble adhesion molecules increased further during the study period (sELAM-1 from 90 +/- 22 to 134 +/- 30 ng/ml; sICAM-1 from 958 +/- 173 to 1460 +/- 209 ng/ml; sVCAM-1 from 1100 +/- 188 to 1804 ng/ml; sGM-140 from 499 +/- 102 to 688 +/- 121 ng/ml) (p < 0.05), whereas in the PTX-treated CVVH patients, plasma levels of all soluble adhesion molecules remained almost unchanged. The PaO2/FIO2 increased in the PTX-treated patients (from 209 +/- 67 to 282 +/- 58 mmHg) and remained almost unchanged in the CVVH control patients. CONCLUSION: Leukocyte/endothelial interactions play an important role in the inflammatory process. Circulating adhesion molecules may serve as markers of the extent of inflammation. Continuous i.v. administration of PTX was successful in blunting the increase of soluble adhesion molecules in critically ill patients undergoing CVVH. Whether these effects result from improved circulation at the microcirculatory level or from (direct or indirect) beneficial effects on endothelial cells warrants further controlled studies.

Acute Kidney Injury↗

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

[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

Volume replacement with gelatin or hydroxyethylstarch solutions does not impair somatosensory evoked potential monitoring: a haemodilution study in conscious volunteers.

The influence of haemodilution with colloids on somatosensory evoked potentials in non-premedicated volunteers is reported. In seven volunteers (randomized crossover design), blood (20 mL kg-1 within 30 min) was removed and simultaneously replaced by gelatin 3% or hydroxyethylstarch 6%. After 30 min, blood was retransfused within 30 min. Median and posterior tibial nerve somatosensory evoked potentials were recorded from the cortex, second cervical vertebra, Erb's point and 1st lumbar vertebra, respectively. One volunteer experienced a severe allergic reaction to gelatin, therefore only six gelatin trials were evaluated. Haemodilution decreased the haematocrit from 39.8 +/- 1.6% (mean +/- SD) to 31.1 +/- 2.0% (gelatin) and from 40.7 +/- 1.7% to 29.8 +/- 1.5 % (hydroxyethylstarch), respectively. Retransfusion increased haematocrit to 34.4 +/- 0.9% (gelatin) and to 34.2 +/- 1.3% (hydroxyethylstarch). Neither haemodilution with gelatin nor haemodilution with hydroxyethylstarch or retransfusion influenced evoked potentials. In conclusion, the treatment of blood loss up to 30% of estimated blood volume with gelatin or hydroxyethylstarch will not affect somatosensory evoked potential monitoring provided normovolaemic conditions are maintained.

Adult↗

PubMed1996

[Adrenergic beta receptors in anesthesia and intensive care medicine].

beta-Adrenoceptors (beta-AR) are divided into a beta 1-, a beta 1-, and a recently cloned beta 3-subtype. beta-AR belong to the group of 7-transmembrane spanners which are coupled via GS-proteins to the enzyme adenylyl cyclase. Instead of being static entities, beta-AR undergo dynamic regulation upon repeated or prolonged exposure to agonists (down-regulation) or antagonists (up-regulation). After exposure to agonists, an early desensitisation caused by phosphorylation of amino acid residues can be distinguished from receptor sequestration. Finally, the internalised receptor is digested by proteolytic enzymes. The present article describes the basic patterns of molecular biology of beta-AR, signal transduction, and receptor desensitisation. In the human heart, beta-AR are the most important receptor system to provide positive inotropic and chronotropic effects. The alterations of the beta-adrenergic system in cardiac insufficiency, after heart transplantation, and after extracorporeal circulation, as well as changes induced by surgery and single anaesthetic agents, are reviewed.

Amino Acid Sequence↗

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

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

Isovolaemic haemodilution with hydroxyethylstarch has no effect on somatosensory evoked potentials in healthy volunteers.

BACKGROUND: An animal study in anaesthetized baboons demonstrated that somatosensory evoked potentials (SSEP) can be affected by extreme haemodilution. This might lead to misinterpretation and reduce the value of intraoperative SSEP monitoring when colloids are administered. In the present study, the effect of haemodilution (HD) and subsequent retransfusion of autologous blood on SSEP was determined in healthy non-premedicated volunteers. METHOD: Acute isovolaemic HD served as a model for blood loss immediately replaced with colloids. In 12 volunteers, 20 ml/kg.bw blood was withdrawn within 30 minutes and simultaneously multaneously replaced with 6% hydroxyethylstarch (HES). 30 minutes later, the autologous blood was retransfused within 30 minutes. Recording sites and parameters were: 1. Median nerve SSEP: cortical, cervical (C2), Erb's point; 2. Posterior tibial nerve SSEP: cortical, cervical (C2), lumbar (L1). In addition to SSEP latency and amplitude, median and tibial nerve central conduction times, spinal conduction time and nerve conduction velocity were determined. Serial SSEP measurements were made before, during and after HD and retransfusion every 15 minutes. RESULTS: HD consisting of a withdrawal volume of 1550 +/- 155 ml (mean +/- SD) induced a decrease in haematocrit from 42.0 +/- 3.1% to 29.6 +/- 1.6% (P < 0.001). Following retransfusion, haematocrit increased to 35.0 +/- 2.1% (P < 0.001). Neither HD nor retransfusion influenced SSEP parameters. CONCLUSION: We conclude from our data that the therapy of blood loss up to 30% of estimated blood volume with HES does not affect SSEP monitoring as long as normovolaemia is maintained.

Adult↗

PubMed1995

[Increase in interleukin-6 plasma concentrations following hypotensive anesthesia with sodium nitroprusside].

In animal models authors have dealt with the question of whether hypotension alone can cause an acute-phase response even in the absence of marked blood loss and trauma. Sodium nitroprusside (SNP), which was employed in the animal models, is also used to induce hypotension in humans. Since no data are available on human subjects plasma concentrations of interleukin-6 (IL-6), an important mediator of the acute-phase response, were studied in patients during SNP infusion for induction of hypotension. METHODS. After approval by the local ethics committee, 20 patients scheduled for elective oto-rhino-laryngological operations participated in this randomised prospective study. Anaesthesia was induced with fentanyl, etomidate, vecuronium and succinylcholine and was maintained with isoflurane in 66% N2O and 33% O2. Ten patients received SNP to reduce mean arterial blood pressure to 50 mmHg, while another ten patients served as controls. Blood samples were taken before the induction of anaesthesia, during surgery (at the end of the SNP infusion), 60 min after surgery and on the day after surgery. IL-6 concentrations were determined by means of enzyme-linked immunosorbent assay. Epinephrine and norepinephrine in plasma were measured by high-pressure liquid chromatography with electrochemical detection. RESULTS. The IL-6 plasma concentration increased significantly from 3.2 (0-7.5) pg/ml (median and range) to 31.8 (9-42.2) pg/ml in the SNP group and from 3.5 (0-8.3) pg/ml to 15.2 (7.4-19) pg/ml in the control group on the morning after surgery. The IL-6 values at this time were significantly (P < 0.05) higher in the SNP group than in the controls. Norepinephrine increased significantly from 263 (150-920) pg/ml (median and range) preoperatively to 419 (115-897) pg/ml, and the epinephrine concentrations rose significantly from 77 (12-159) pg/ml to 115 (83-330) pg/ml at the end of SNP administration. No significant changes in the catecholamine concentrations were observed in the control group. CONCLUSIONS. The SNP infusion exerted an important additional stimulus for IL-6 release after relatively mild surgical trauma in both groups. This finding is probably due to the liberation of NO from the SNP molecule and an increase in the intracellular concentration of cGMP. The elevation of the plasma catecholamines immediately after SNP administration should also be taken into account, because an augmentation of the cAMP in various cell types has been proven to result in increased release of IL-6.

Adult↗

PubMed1995

[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↗

PubMed1995

[Does controlled hypotension with nitroprusside affect platelet function?].

Induced hypotension is an accepted technique to reduce intraoperative blood loss and thereby ensures satisfactory operating conditions, especially in microscopic interventions. Sodium nitroprusside (NP), which is often used for induced hypotension, was reported to inhibit platelet aggregation in vitro. Impairment of platelet function implies a higher bleeding risk, which would make the use of NP for induced hypotension questionable. METHODS. With the approval of the local ethics committee, 30 patients scheduled for nasal septum operations were included in this randomised study. For induction of anaesthesia 2 mg vecuronium, 0.1 mg fentanyl, 0.2 mg/kg etomidate, and 1 mg/kg succinylcholine were used. After tracheal intubation the patients inhaled 1.0-1.5 vol.% isoflurane in a gas mixture containing 66% nitrous oxide in oxygen. Fifteen patients received an i.v. infusion of NP for 60 min. The concentrations chosen produced a decrease of mean arterial blood pressure to 50 mm Hg. Blood samples were taken before induction of anaesthesia; after induction of anaesthesia but before beginning of the operation; and 60 min after the beginning of the operation. This time-point coincided with the end of NP administration in the study group. The last blood sample was drawn the morning after the operation. Platelet function was determined in platelet-rich plasma by a turbidometric method after adding 22 mumol/l epinephrine to induce aggregation. The spontaneous aggregation was measured in whole blood using impedance aggregometry. Data within one group were analysed using analysis of variance. Student's t-test for unpaired values served to compare data between the two groups. RESULTS. Biometric data in the two groups were comparable. The blood loss in the control group [265 (190-410) ml] significantly exceeded (P < 0.05) that in the hypotensive group [125 (75-210) ml]. No significant changes in platelet function were found throughout the study period in the patients treated with NP. In the control patients the epinephrine-induced aggregation increased significantly from 53.1 +/- 5.3% before anaesthesia to 72.1 +/- 3.3% the morning after the intervention. The spontaneous aggregation showed a significant increase from 0.718 +/- 0.338 Ohm/h before anaesthesia to 2.164 +/- 0.442 Ohm/h 60 min after the beginning of the operation. The value on the 1st postoperative day (2.266 +/- 0.448 Ohm/h) was also significantly higher than the basal value. CONCLUSIONS. In contradiction to in vitro studies using high concentrations of NP, we could not find a decrease in platelet aggregation due to hypotensive anaesthesia with this drug in vivo. In the control group a significant increase in platelet aggregation was observed, which was probably counteracted in the hypotensive patients by the interaction of NP with cyclic guanosine monophosphate (c-GMP). NP augments the intracellular concentration of c-GMP, which is known to decrease platelet aggregation.

Adolescent↗