Improved oxygen delivery by positive pressure ventilation with continuous negative external chest pressure.
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Functional Residual Capacity↗
Biomedical subjects
G Hempelmann
Publications and source records attributed to G Hempelmann.
[Clinical significance of S-(+)-ketamine].
Among anaesthetic drugs, ketamine occupies a special position. biochemically, ketamine is a racemate consisting of equal shares of two optical enantiomers. Pharmacological investigations show differences between those enantiomers in both qualitative and quantitative properties. Furthermore, clinical superiority of S-(+)-ketamine has been described in different therapeutic studies with regard to anaesthetic potency, the extent of analgesia, effects and side effects during and after the operation, and undiserable psychological dysfunction. On a neuropharmacological basis, the clinical superiority of S-(+)-ketamine is due to its effect on NMDA receptors in central nervous tissue, opioid receptors on both central and peripheral levels, and noradrenergic, dopaminergic, and serotoninergic mechanisms. The main problems associated with the ketamine racemate in clinical use are desirable psychological dysfunction and a prolonged period of arousal. There are grounds for the assumption that the use of S-(+)-ketamine will minimise those problems without reducing anaesthetic potency or restricting the advantages of ketamine anaesthesia.
Anesthetics, General↗
[Transcranial doppler sonography. Effect of sevoflurane in comparison to isoflurane].
METHODS: Using transcranial Doppler sonography (TCD), we studied the effects of sevoflurane compared to equipotent doses of isoflurane on blood-flow velocity in the middle cerebral artery (MCA) before, during, and after general anaesthesia. In random order, 30 patients received sevoflurane (n = 15) or isoflurane (n = 15) given in stepwise-increasing doses of 0.5, 1.0, and 1.5 MAC in oxygen/air (FiO2 = 0.5). Oxygen/air was then replaced by oxygen/nitrous oxide 33%/65% with decreasing doses (1.5, 1.0, 0.5 MAC) of sevoflurane or isoflurane. During each step, ventilation was controlled to provide first normocapnia (end-tidal pCO2 = 38 mmHg) and then hypocapnia (end-tidal pCO2 = 27 mmHg). MCA blood-flow velocity and pulsatility, arterial blood pressure, heart rate, and body temperature were recorded simultaneously at the end of each period. For statistical analysis, within-group comparison was made by one-way ANOVA. Differences between groups were determined by two-way analysis of variance. Age, weight, and height of the patients were compared using Student's t-test; P < 0.05 was considered significant. RESULTS: Groups were comparable regarding age, weight, and height. TCD parameters were not significantly changed by increasing doses of sevoflurane or isoflurane given in oxygen/air when compared to the awake data. However, increasing MCA blood-flow velocity was found with decreasing doses of sevoflurane or isoflurane given in oxygen/nitrous oxide (P < 0.05 for 0.5 MAC, normoventilation) without intergroup, differences. In both groups, hyperventilation always decreased MCA blood-flow velocity. CONCLUSIONS: We conclude from our TCD data that equipotent doses of sevoflurane and isoflurane comparably affect cerebral perfusion, especially when nitrous oxide is given simultaneously.
Adolescent↗
Does continuous heparinization influence platelet function in the intensive care patient?
OBJECTIVE: To study the influence of continuous administration of heparin on platelet function in intensive care patients. DESIGN: Prospective, serial investigation. SETTING: Clinical investigation on a surgical and neurosurgical intensive care unit in a university hospital. PATIENTS: The study included 45 patients: 15 postoperative with patients sepsis (Acute Physiology and Chronic Health Evaluation II score between 15 and 25), 15 trauma patients (Injury Severity Score 15 to 25), and 15 neurosurgical patients. INTERVENTIONS: Management of the patients was carried out according to the guidelines for modern intensive care therapy. Sepsis and trauma patients received standard (unfractionated) heparin continuously [aim: an activated partial thromboplastin time (aPTT) approximately 2.0 times normal value; sepsis-heparin and trauma-heparin patients], whereas neurosurgical patients received no heparin (neurosurgical patients). MEASUREMENTS AND RESULTS: From arterial blood samples, platelet aggregation was measured by the turbidimetric method. Platelet aggregation was induced by adenosine diphosphate (ADP; 2.0 mumol/l), collagen (10 micrograms/ml), and epinephrine (25 mumol/l). Measurements were carried out on the day of diagnosis of sepsis or 12 h after hemodynamic stabilization (trauma and neurosurgery patients) (baseline) and during the next 5 days at 12.00 noon. Standard coagulation parameters [platelet count and fibrinogen and antithrombin III (AT III) plasma concentrations] were also monitored. Heparin 4-10 U/kg per h (mean dose: approximately 500 U/h) was necessary to reach an aPTT of about 2.0 times normal. Platelet count was highest in the neurosurgical patients, but it did not decrease after heparin administration to the trauma and sepsis patients. AT III and fibrinogen plasma levels were similar in the three groups of patients. In the sepsis group, platelet aggregation variables decreased significantly (e.g., epinephrine-induced maximum platelet aggregation:-45 relative % from baseline value). Platelet function recovered during the study and even exceeded baseline values (e.g., ADP-induced maximum platelet aggregation: +42.5 relative % from baseline value). Continuous heparinization did not blunt this increase of platelet aggregation variables. In the heparinized trauma patients, platelet aggregation variables remained almost stable and were no different to platelet aggregation data in the untreated neurosurgical patients. CONCLUSIONS: Continuous administration of heparin with an average dose of approximately 500 U/h did not negatively influence platelet function in the trauma patients. Recovery from reduced platelet function in the sepsis group was not affected by continuous heparinization. Thus, continuous heparinization with this dose appears to be safe with regard to platelet function in the intensive care patient.
APACHE↗
What the neurosurgeon needs to know about the coagulation system.
Intracranial surgery is often complicated by thromboembolic events including the life-threatening pulmonary embolism. After head trauma and in patients with brain tumors disseminated intravascular coagulation (DIC) can occur, characterized by the triggering of the coagulation cascade and the depletion of coagulation factors which ultimately leads to bleeding. The identification of patients at high risk as well as the early diagnosis of hemostatic problems uses routine laboratory parameters such as partial thromboplastin time and prothrombin time reflecting the intrinsic and the extrinsic pathway of the coagulation respectively. Thrombin antithrombin III complexes (TAT) and prothrombin fragment 1 + 2 (F1 + 2) are further indicators of an activation of the coagulation whereas fibrinogen degradation products (FDP) refer to the fibrinolytic system. The basic principles of coagulation and fibrinolysis are summarized as well as the changes of laboratory parameters accompanying DIC, hypercoagulability and hyperfibrinolysis.
Blood Coagulation↗
The influence of acute preoperative plasmapheresis on coagulation tests, fibrinolysis, blood loss and transfusion requirements in cardiac surgery.
OBJECTIVE: Withdrawal of autologous plasma and reinfusion after cardiopulmonary bypass (CPB) offers the opportunity of improving patients' haemostasis and reducing homologous blood consumption in cardiac surgery. The influence of acute, preoperative plasmapheresis (APP) on coagulation tests, fibrinolysis, blood loss and transfusion requirements was investigated in elective aortocoronary bypass patients. METHODS: Forty patients were randomized to a control or pheresis group. The pheresis group had platelet-rich plasmapheresis (PRP-group, n = 20) performed before incision and the platelet-rich plasma (PRP) was returned after CPB. The control group (n = 20) was managed without pheresis. All patients had serial coagulation studies, including prothrombin split products (F1/F2), fibrinopeptide A (FPA), protein C (PC), thrombomodulin (TM), tissue-plasminogen-activator (t-PA), plasminogen-activator-inhibitor (PAI 1), fibrinopeptide B beta 15-42 (FPB beta 15-42), haemoglobin and platelet counts determined intra- and postoperatively. Chest tube drainage and transfusion requirements were recorded. RESULTS: APP had no negative effects on the quality of PRP. The platelet count of the withdrawn autologous plasma was 239 +/- 33 x 10(9)/l. From the end of the operation (after retransfusion of autologous plasma) until the first postoperative day platelet counts were significant higher in the PRP-group (P > 0.05). Plasma concentrations of modified antithrombin III (ATM), F1/F2 and FPA increased (166-290% from baseline) and PC- and TM-antigen decreased (11-49% from baseline) to a different extent for both groups throughout CPB. t-PA-activity increased intraoperatively peaking at the end of CPB (PRP-group: 4.8 +/- 0.8 IU/ml, control-group: 8.1 +/- 2.3 IU/ml)(P > 0.05). With onset of CPB PAI-1 levels decreased and were further reduced after CPB in control patients in comparison to PRP-patients (P < 0.05). FPB beta 15-42 occurred in peak concentrations after neutralisation of heparin by protamine. Only PRP-patients showed baseline values of coagulation and fibrinolytic parameters on the next morning (P < 0.05). Total postoperative blood loss during the first 24 h was 503 +/- 251 ml (PRP-group) and 937 +/- 349 ml in the control-group (P < 0.05). None of the PRP-patients received allogeneic blood, whereas five control-patients received 11 units of packed red cells (P < 0.05). CONCLUSIONS: The findings suggest that in elective cardiac surgery heparin cannot prevent generation of both thrombin and fibrin, born throughout CPB and postoperatively. The use of PRP withdrawn immediately preoperatively is an attractive technique to reduce allogeneic blood usage and preoperative blood loss, especially in patients in whom withdrawal of autologous whole blood cannot be performed.
Aged↗
Plasma levels of immunoinhibitory cytokines interleukin-10 and transforming growth factor-beta in patients undergoing coronary artery bypass grafting.
OBJECTIVE: Cardiovascular surgery with extracorporeal circulation causes a systemic inflammatory response, which can lead to organ failure and increased postoperative morbidity. Advances in knowledge about the interactions between markers of cellular and humoral immunity involved in the inflammatory response to cardiopulmonary bypass (CPB) may reduce the deleterious effects and improve the outcome for patients undergoing cardiac surgery. METHODS: To determine the release of immunoinhibiting cytokines during CPB, we measured plasma levels of interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) in 30 patients undergoing elective coronary artery bypass grafting. Arterial blood samples were collected at eight time points before, during and after CPB, using a standardized ELISA-technique. RESULTS: Plasma IL-10 and TGF-beta increased significantly after weaning off CPB (P < 0.05) and peaked respectively at time of skin closure (IL-10, 308 +/- 180 pg/ml; TGF-beta, 1860 +/- 906 pg/ml; mean peak +/-S.D.). Postoperatively, 6 h, IL-10 decreased to 19.8 +/- 9.8 pg/ml (P < 0.05) and TGF-beta decreased to 1133 +/- 547 pg/ml (P < 0.05). CONCLUSIONS: Both cytokines are major immunoregulatory factors with negative influence on T cell-mediated immunologic response. The significantly elevated levels at the end of CPB indicate that IL-10 and TGF-beta may be important factors of immunologic dysregulation following CPB.
Adult↗
Concentration of cefamandole in plasma and tissues of patients undergoing cardiac surgery: the influence of different cefamandole dosage.
OBJECTIVE: To develop an improved regimen of antibiotic prophylaxis in cardiac surgery, three antibiotic prophylactic regimens for patients scheduled to have elective cardiothoracic surgery involving a median sternotomy were evaluated. DESIGN: A prospective, randomized, unblinded study. SETTING: A university teaching hospital. PARTICIPANTS: Sixty-nine men scheduled for elective coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) were included in the study. INTERVENTIONS: The patients were selected at random to receive 2 g of cefamandole (CM) at induction of anesthesia (group 1, n = 24), or 2 g of CM at the beginning of anesthesia followed by an additional dose (2 g) immediately after onset of cardiopulmonary bypass (CPB) (group 2, n = 22), or 4 g of CM just at the initiation of anesthesia (group 3, n = 23). Samples from the mammary artery, sternum, and plasma were obtained at various intervals after injection of the antibiotic (10 minutes intravenously) to compare antibiotic levels, assayed for CM concentrations, with high-pressure liquid chromatography (HPLC) and plasma bactericidal activity as well as infectious complications in these sites as a function of time for the three groups. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in biometric data, duration of hospitalization, or management of cardiopulmonary bypass, including urinary tract drainage and infusion volume. The mean plasma t1/2 (distributive or alpha-phase) before bypass was 51.7 +/- 16.7 minutes for group 1 and 2 patients and 54.9 +/- 15.9 minutes for group 3 patients. CM plasma values were significantly higher in group 2 (170.3 +/- 105.8 micrograms/mL) than in groups 1 and 3 (111.8 +/- 42.2 micrograms/mL, 101.2 +/- 57.2 micrograms/mL) at the end of bypass periods (p < 0.05). The antibiotic contents of mammary artery and sternum samples of group 2 (15.6 +/- 4.7 micrograms/mL, 9.5 +/- 4.7 micrograms/mL) were significantly higher after completion of CPB compared with group 1 (5.7 +/- 1.9 micrograms/mL, 3.8 +/- 2.9 micrograms/mL) and group 3 (6.3 +/- 3.5 micrograms/mL, 3.6 +/- 1.8 micrograms/mL) (p < 0.05). There were no significant differences in distribution of micro-organisms among the three groups, but two patients of groups 1 and 3 with plasma and tissue CM levels below minimal inhibitor concentration (MIC90) for Hemophilus influencea, E coli, Proteus ssp and Klebsiella ssp after completion of CPB, respectively, developed a pneumonia postoperatively caused by Hemophilus influencea (1), E coli (1) and Klebsiella ssp (2) (p < 0.05). CONCLUSIONS: It would be preferable to infuse the antibiotic shortly before the operative procedure. However, to keep tissue and plasma CM values more than MIC90 for common pathogens during the time period studied, a second infusion of 2 g of CM administered after onset of CPB suggests better protection against the risk of microbial infections. Therefore, the findings might be important for the choice of antibiotic prophylaxis, particularly for high-risk patients.
Adult↗
[Discussion of the pulmonary artery catheter].
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Catheterization, Swan-Ganz↗
Blocking mechanisms of ketamine and its enantiomers in enzymatically demyelinated peripheral nerve as revealed by single-channel experiments.
BACKGROUND: Ketamine shows, besides its general anesthetic effect, a local anesthetic-like action that is due to blocking of peripheral nerve sodium currents. In this study, the stereoselectivity of the blocking effects of the ketamine enantiomers S(+) and R(-) was investigated in sodium and potassium channels in peripheral nerve membranes. METHODS: Ion channel blockade of ketamine was investigated in enzymatically dissociated Xenopus sciatic nerves in multiple-channel and in single-channel outside-out patches. RESULTS: Concentration-effect curves for the Na+ peak current revealed half-maximal inhibiting concentrations (IC50) of 347 microM and 291 microM for S(+) and R(-) ketamine, respectively. The potential-dependent K+ current was less sensitive than the Na+ current with IC50 values of 982 microM and 942 microM. The most sensitive ion channel was the flickering background K+ channel, with IC50 values of 168 microM and 146 microM for S(+) and R(-) ketamine. Competition experiments suggest one binding site at the flicker K+ channel, with specific binding affinities for each of the enantiomers. For the Na+ channel, the block was weaker in acidic (pH = 6.6) than in neutral (pH = 7.4) and basic (pH = 8.2) solutions; for the flicker K+ channel, the block was weaker in acidic and stronger in basic solutions. CONCLUSIONS: Ketamine blockade of sodium and potassium channels in peripheral nerve membranes shows no stereoselectivity except for the flicker K+ channel, which showed a very weak stereoselectivity in favor of the R(-) form. This potential-insensitive flicker K+ channel may contribute to the resting potential. Block of this channel and subsequent depolarization of the resting membrane potential leads, besides to direct Na+ channel block, to inexcitability via Na+ channel inactivation.
Anesthetics, Dissociative↗
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↗
ATP-dependent potassium channel in rat cardiomyocytes is blocked by lidocaine. Possible impact on the antiarrhythmic action of lidocaine.
BACKGROUND: During myocardial ischemia, lidocaine has favorable antiarrhythmic properties. Malignant arrhythmias result from heterogeneity between ischemic and nonischemic regions in extracellular potassium concentration and action potential duration. These effects have been attributed to the activation of ATP-dependent potassium (KATP) channels. In this study, we investigated the action of lidocaine on the KATP channels to test the possible link between the antiarrhythmic properties of lidocaine and its action on the KATP channel. METHODS AND RESULTS: The patch-clamp technique was employed on enzymatic dissociated cardiomyocytes of adult rats. Lidocaine was applied to the outer side of excised membrane patches by means of a multibarrel perfusion system. Lidocaine reversibly blocked the mean current of the KATP channels in a concentration-dependent manner (IC50 = 43 +/- 4.7 mumol/L, E = 0 mV, n = 6), while the amplitude of the single-channel current remained unchanged. The half-maximum blocking concentration corresponds to the therapeutic range for the antiarrhythmic application of a lidocaine bolus in humans. CONCLUSIONS: The open probability but not the conductance of the KATP channel in the membrane of rat cardiomyocytes is blocked by lidocaine. This action may explain, in part, the favorable antiarrhythmic properties of lidocaine during acute myocardial ischemia.
Adenosine Triphosphate↗
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↗
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↗
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↗
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↗
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↗
[NO inhalation in heart surgery procedures: relevance for right heart function?].
UNLABELLED: The right ventricle is more jeopardized by a cardiopulmonary bypass than the left one. Impaired right ventricular performance may profit from an afterload reduction. A selective reduction in pulmonary artery pressure (PAP) or pulmonary vascular resistance (PVR) without impairment of the systemic circulation seems to be possible by inhalation of nitric oxide (NO). Therefore in the present study we looked for influences of NO inhalation on PAP, PVR and right heart parameters immediately after weaning from the bypass. The dependence of endothelial function on age, preoperative heart function and extracorporeal circulation is well established. The relevance of such parameters on NO inhalation was also investigated. METHODS: After ethical approval and informed consent were obtained, 20 patients with moderately increased PAP were included in the study. Ten patients inhaled NO at a concentration of 30 ppm; the other group served as a control group. Measurement points were 10 min after the end of extracorporeal circulation (baseline), 3, 10, and 20 min after the start, as well as 10 min after the end of NO inhalation. NO was injected near the tube into the tubing system during inspiration; dosage and monitoring of the concentration were achieved by means of a chemiluminometer. Measured parameters consisted of PAP, PVR, right ventricular ejection fraction and volumes, systemic blood pressure and resistance, central venous pressure, pulmonary capillary wedge pressure, and oxygenation parameters (paO2, pvO2, paCO2). RESULTS: The decrease in PAP (from 29.7 +/- 3.9 to a minimal 25.4 +/- 4.3 mm Hg, P < 0.005) and in PVR (from 169.4 +/- 51.9 to a minimal 116.3 +/- 60.9 dyn.s.cm-5, P.0.05) did not improve right heart function. A similar significant increase in SVR was observed in the NO group and in the control group. Age, haemodynamic parameters or duration of the ischaemic phase of the cardiopulmonary bypass did not influence the course of PAP or PVR. Changes in PAP (from 30.0 +/- 4.0 to a minimal 26.7 +/- 3.6 mm Hg, P < 0.05) and PVR (from 149.0 +/- 41.5 to a minimal 125.2 +/- 51.5 dyn.s.cm-5, in the control group were not statistically different from those in the NO group. Indicators of intoxication like an increase in NO2 or methaemoglobin concentrations or changes in compliance or resistance were not observed. CONCLUSIONS: Patients with moderate pulmonary hypertension did not profit from NO inhalation immediately after weaning from the cardiopulmonary bypass. The decreases in PAP and PVR found in the NO or control group did not improve right-heart function. When the NO and control group were compared, specific effects of NO inhalation on PAP and PVR must be questioned. This could perhaps be explained by data from animal experiments, which found high endogenous NO levels in situations with elevated cytokine levels. Cytokines are increased after extracorporeal circulation. Oxygenation was not impaired by inhalation of relatively high concentrations of NO. For all investigations with NO inhalation not preceded by steady-state conditions, a control group is recommended.
Aged↗