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Biomedical subjects

G Hempelmann

Publications and source records attributed to G Hempelmann.

At least 163 records · Page 9Linked to original sources
PubMed1998

Blockade of Na+ and K+ currents by local anesthetics in the dorsal horn neurons of the spinal cord.

BACKGROUND: The dorsal horn of the spinal cord is a pivotal point for transmission of neuronal pain. During spinal and epidural anesthesia, the neurons of the dorsal horn are exposed to local anesthetics. Unfortunately, little is known about the action of local anesthetics on the major ionic conductances in dorsal horn neurons. In this article, the authors describe the effects of bupivacaine, lidocaine, and mepivacaine on voltage-gated Na+ and K+ currents in the membranes of these neurons. METHODS: The patch-clamp technique was applied to intact dorsal horn neurons from laminae I-III identified in 200-microm slices of spinal cord from newborn rats. Under voltage-clamp conditions, the whole-cell Na+ and K+ currents activated by depolarization were recorded in the presence of different concentrations of local anesthetics. RESULTS: Externally applied bupivacaine, lidocaine, and mepivacaine produced tonic block of Na+ currents with different potencies. Half-maximum inhibiting concentrations (IC50) were 26, 112, and 324 microM, respectively. All local anesthetics investigated also showed a phasic, that is, a use-dependent, block of Na+ channels. Rapidly inactivating K+ currents (KA currents) also were sensitive to the blockers with IC50 values for tonic blocks of 109, 163, and 236 microM, respectively. The block of KA currents was not use dependent. In contrast to Na+ and KA currents, delayed-rectifier K+ currents were almost insensitive to the local anesthetics applied. CONCLUSIONS: In clinically relevant concentrations, local anesthetics block Na+ and KA currents but not delayed-rectifier K+ currents in spinal dorsal horn neurons. The molecular mechanisms of Na+ and K+ channel block by local anesthetics seem to be different. Characterization of these mechanisms could be an important step in understanding the complexity of local anesthetic action during spinal and epidural anesthesia.

Anesthetics, Local↗
PubMed1998

Influence of angiotensin-converting enzyme inhibitor enalaprilat on endothelial-derived substances in the critically ill.

OBJECTIVE: To assess the effects of the angiotensin-converting enzyme inhibitor enalaprilat on endothelial cells in septic patients. DESIGN: Prospective, randomized, placebo-controlled, blinded study. SETTING: Clinical investigation on a surgical intensive care unit of a university hospital. PATIENTS: Forty surgical septic patients (noncardiac/nonneurosurgical patients). INTERVENTIONS: After inclusion in the study and after baseline data were obtained, either 0.25 mg/hr (enalaprilat group, n = 20) or saline solution as placebo (control group, n = 20) was continuously given and continued throughout the following 5 days. MEASUREMENTS AND MAIN RESULTS: Extensive hemodynamic monitoring was carried out in all patients. Plasma concentrations of endothelin-1, angiotensin II, soluble thrombomodulin, and soluble adhesion molecules (endothelial leukocyte adhesion molecule-1, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and granule membrane protein-140) were measured from arterial blood samples. All measurements were carried out before the start of the infusion ("baseline" values) and daily during the following 5 days. All endothelial-derived substances (thrombomodulin, endothelin-1, and all soluble adhesion molecules) were similarly increased beyond normal in both group. Endothelin-1 increased only in the untreated control patients (from 6.9 +/- 0.7 to 14.3 +/- 1.4 mg/mL). Soluble thrombomodulin increased in the untreated control patients (from 58 +/- 9 to 79 +/- 14 ng/mL [p < .05]), but significantly decreased in the enalaprilat-treated patients. Soluble adhesion molecules increased in the untreated control group (endothelial leukocyte adhesion molecule from 92 +/- 14 to 192 +/- 29 ng/mL; intercellular adhesion molecule-1 from 480 +/- 110 to 850 +/- 119 ng/ mL) and returned almost to normal values in the enalaprilat patients. The survival rate did not differ significantly between the two groups. Control patients developed severe sepsis and septic shock more often than the enalaprilat-treated group. CONCLUSIONS: The complex pathogenesis of endothelial function abnormalities in sepsis may offer a large number of pharmacologic interventions. Administration of the angiotensin-converting enzyme inhibitor enalaprilat resulted in a reduced release of soluble endothelial-derived substances into the circulating blood, which may indicate an improved endothelial function. The specific actions of enalaprilat on the endothelium have to be elucidated in further studies.

Aged↗
PubMed1998

Modulation of somatosensory evoked potentials under various concentrations of desflurane with and without nitrous oxide.

Continuous measurement of somatosensory evoked potentials (SEP) by means of characteristic changes in the signal pattern makes it possible to identify cerebral or spinal cord ischemia during critical phases of the operative procedure. A correct interpretation of the measurements is only possible, however, if the influence of drugs acting on the central nervous system is known. The authors were able to show that inhaled anesthetics have an impact on latencies and response amplitudes. This study examined the influence of various concentrations of desflurane on the conduction of SEP of the Median nerve. In addition, the authors determined how the supplementation of nitrous oxide (N2O) influences the stimulus response of the medianus nerve's SEP. Desflurane has been shown to produce dose-dependent increases in SEP latency (data in part for latency N2O: 0.5 minimum alveolar concentration [MAC] = 20.8 +/- 0.9; 1.5 MAC = 22.2 +/- 1.5; 1.5 MAC/N2O= 23.8 +/- 1.5) and decreases in amplitude, whereas cervically recorded subcortical SEP components are minimally influenced by desflurane. When nitrous oxide is added, there were marked reductions in amplitude (p<0.01) of the cortical stimulus response (1.5 MAC = 2.4 +/- 0.9; 1.5 MAC/N2O = 1.1 +/- 1). It can therefore be recommended that supplementation with N2O should be avoided in the presence of low initial amplitudes. Based on the study's results, the use of desflurane (up to 1.0 MAC) seems to be compatible with intraoperative monitoring of median somatosensory evoked potentials.

Anesthesia, Inhalation↗
PubMed1998

Retracted: Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery.

BACKGROUND: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. METHODS: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 micrograms.kg-1.min-1 of dopexamine (n = 15) or placebo (n = 15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. RESULTS: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61 +/- 0.41 to 4.57 +/- 0.78 l.min-1.m-2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO2I) and oxygen consumption index (VO2I) were also significantly increased in the dopexamine group (DO2I: from 416 +/- 91 to 717 +/- 110 ml/m2.m2; VO2I: from 98 +/- 25 to 157 +/- 22 ml/m2.m2), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37 +/- 1.1 to 35.9 +/- 12.1 pg/ml; ET-1: from 2.88 +/- 0.91 to 6.91 +/- 1.20 pg/ml). CONCLUSION: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.

Adrenergic beta-Agonists↗
PubMed1998

Complex blockade of TTX-resistant Na+ currents by lidocaine and bupivacaine reduce firing frequency in DRG neurons.

Mechanisms of blockade of tetrodotoxin-resistant (TTXr) Na+ channels by local anesthetics in comparison with the sensitivity of tetrodotoxin-sensitive (TTXs) Na+ channels were studied by means of the patch-clamp technique in neurons of dorsal root ganglions (DRG) of rat. Half-maximum inhibitory concentration (IC50) for the tonic block of TTXr Na+ currents by lidocaine was 210 micromol/l, whereas TTXs Na+ currents showed five times lower IC50 of 42 micromol/l. Bupivacaine blocked TTXr and TTXs Na+ currents more potently with IC50 of 32 and 13 micromol/l, respectively. In the inactivated state, TTXr Na+ channel block by lidocaine showed higher sensitivities (IC50 = 60 micromol/l) than in the resting state underlying tonic blockade. The time constant tau1 of recovery of TTXr Na+ channels from inactivation at -80 mV was slowed from 2 to 5 ms after addition of 10 micromol/l bupivacaine, whereas the tau2 value of approximately 500 ms remained unchanged. The use-dependent block of TTXr Na+ channels led to a progressive reduction of current amplitudes with increasing frequency of stimulation, which was </=53% block at 20 Hz in 10 micromol/l bupivacaine and 81% in 100 micromol lidocaine. The functional importance of the use-dependent block was confirmed in current-clamp experiments where 30 micromol/l of lidocaine or bupivacaine did not suppress the single action potential but clearly reduced the firing frequency of action potentials again with stronger potency of bupivacaine. Because it was found that TTXr Na+ channels predominantly occur in smaller sensory neurons, their blockade might underlie the suppression of the sensation of pain. Different sensitivities and varying proportions of TTXr and TTXs Na+ channels could explain the known differential block in spinal anesthesia. We suggest that the frequency reduction at low local anesthetic concentrations may explain the phenomenon of paresthesia where sensory information are suppressed gradually during spinal anesthesia.

Action Potentials↗
PubMed1998

Acute phase and opsonin response in cardiac surgery patients: influence of underlying cardiac disease.

Cardiopulmonary bypass (CPB) leads to an activation of plasma cascade systems, complement activation, and an acute phase response. To evaluate the influence of the underlying cardiac disease on the activation pattern of these systems, we compared inflammatory changes in coronary artery bypass grafting (CABG) patients with patients undergoing aortic valve replacement. We investigated changes of the acute phase proteins alpha 1-proteinase inhibitor and fibrinogen, the unspecific opsonin fibronectin, and the complement components C3c and C4 induced by extracorporeal circulation in 12 patients undergoing aortic valve replacement and in 12 patients undergoing CABG. Concentrations of C3c and C4 decreased in both groups after the onset of CPB and C4 concentration remained below post-induction levels up to 24 h after onset of CPB (p = 0.04). Fibronectin levels dropped immediately before the onset of CPB (p = 0.01), reaching the lowest values after 20 min of extracorporeal circulation. Fibrinogen and alpha 1-proteinase inhibitor levels after induction of anaesthesia were significantly higher in the CABG group and remained higher throughout the entire study period (p < 0.001). As an indicator of a postoperative acute phase response, concentrations of both proteins rose in the postoperative period above post-induction levels (p < 0.02).

Acute-Phase Reaction↗
PubMed1997

[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↗
PubMed1997

[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↗
PubMed1997

[The effects of dopexamine. Transpulmonary shunt volume in thoracic surgical procedures with one-lung respiration].

OBJECTIVE: To study the influence of dopexamine on pulmonary shunt and hypoxic pulmonary vasoconstriction during major thoracic surgery with one-lung ventilation (OLV). DESIGN: Prospective, randomised, placebo-controlled study. SETTING: University hospital. PATIENTS: Twenty adult patients undergoing elective pulmonary resection. ANAESTHESIA: General anaesthesia was performed using propofol, fentanyl, N2O and vecuronium. Volume-controlled ventilation was performed to maintain normocapnia over the whole investigation period. During OLV, the tidal volume was reduced and the respiratory rate was increased to avoid a peak airway pressure exceeding 40 cm H2O. Furthermore the FiO2 was increased to 1.0 and the external PEEP was removed during OLV. INTERVENTIONS: The patients received either dopexamine at 2 micrograms/kg/min (group A, n = 10) or 0.9% saline as control (group B, n = 10) after assessing the baseline values. MEASUREMENT AND RESULTS: The following cardiorespiratory variables were recorded: Heart rate, mean arterial pressure and mean pulmonary arterial pressure. Cardiac output was measured by thermodilution using a continuous cardiac output thermodilution catheter. Arterial and mixed venous blood gas analysis were measured from simultaneously drawn samples. Cardiac index (CI), systemic vascular resistance index, pulmonary vascular resistance index, oxygen delivery index (DO2I), oxygen consumption index and the venous admixture were calculated using standard formula. Furthermore, pressure-flow-curves were constructed to analyse flow independent changes in the pulmonary vascular resistance. Data were recorded at the following times: After induction of anaesthesia in stable haemodynamics during two-lung ventilation (baseline values, T0), intraoperatively during one-lung ventilation (T1) and postoperatively after re-establishing two-lung ventilation (T2). Patients characteristics, data from the preoperative lung function testing and surgical procedures did not differ significantly between the groups. CI increased in the dopexamine group from 2.5 +/- 1.2 1.min-1.m-2 (T0) to 3.6 +/- 0.9 l.min-1.m-2 (T1) and 4.0 +/- 1.3 l.min-1.m-2 (T2). The course of the intrapulmonary right-to-left shunting did not differ between the groups. In the dopexamine-treated group the DO2I increased from 430 +/- 143 ml.min.m-2 (T0) to 652 +/- 255 ml.min.m-2 (T1) and 653 +/- 207 ml.min.m-2 (T2). Regarding the pressure-flow-curves there was no difference during OLV between the two groups indicating no major blocking effect of dopexamine on hypoxic pulmonary vasoconstriction. CONCLUSION: It is concluded that dopexamine can be used to improve haemodynamics and oxygen delivery during thoracic surgery without increasing venous admixture during one-lung ventilation.

Aged↗
PubMed1997

[The effect of needle type and immobilization on postspinal headache].

UNLABELLED: Post-dural puncture headache (PDPH) is a significant complication of spinal anaesthesia. Diameter and tip of the needle as well as the patient's age have been proven to be important determinants. The question of whether post-operative recumbency can reduce the risk of PDPH has not been answered uniformly. And besides, some studies referring to this subject reveal methodical failures, for example, as to clear definition and exact documentation of post-operative immobilization. Furthermore, fine-gauge needles (26G or more) have not been investigated yet. The first aim of our study was therefore to examine the role of recumbency in the prevention of PDPH under controlled conditions using thin needles. Secondly, we wanted to confirm the reported prophylactic effect of needles with a modified, atraumatic tip (Whitacre and Atraucan) by comparing them to Quincke needles of identical diameter. Most of the former investigators compared Quincke with atraumatic needles of different size regardless of the known influence of the diameter on PDPH. PATIENTS AND METHODS: In a prospective study we included 481 consecutive patients undergoing a total of 500 orthopaedic operations under spinal anaesthesia. The latter was performed in a standardized manner (patient sitting, midline approach, needle with parallel bevel direction), using four different needles allocated randomly (26-gauge and 27-gauge needles with Quincke tip, 26-gauge Atraucan and 27-gauge Whitacre cannula). Half of the patients were instructed to stay in bed for 24 h (horizontal position without raising head), the others to get up as early as possible. An anaesthesiologist visited the patients on the fourth postoperative day or later and questioned them about headache and duration of recumbency. Additionally, the patients had to fill out a questionnaire 1 week after surgery. Any postural headache was considered as PDPH. RESULTS: The four groups of different needles had homogeneous demographic characteristics (see Table 1). A total of 47 patients (9.4%) developed PDPH. The incidence was highest after puncture with a 26-gauge Quincke cannula (17.6%) with a significant difference compared to the other needles (see Table 2). PDPH incidence correlated well with increasing age and number of dural punctures, but showed no relation to sex, patient's history of headache or experience of the anaesthesiologist. Only about half of the patients (60.5%) followed the instructions regarding mobilization or recumbency. The duration of strict bed rest did not influence the development of PDPH: The overall incidence was 9.4% in the recumbency group and 8.8% in the group of early ambulation. In all, 45 patients suffered from ordinary not posture-related headache. CONCLUSIONS: The significantly higher incidence of PDPH after spinal anaesthesia with 26-gauge Quincke needles compared to the 27-gauge Quincke and the 26-gauge Atraucan group confirmed the importance of both needle diameter and design of its tip. The Atraucan cannula has not been examined in a controlled study (in comparison with Quincke needle of the same diameter) before. In accordance with other investigators we found patient's age and number of puncture attempts as additional predictors of PDPH. Consequent bed rest, however, was not able to reduce its incidence. Our studies reveal the poor compliance of patients with regard to mobilization/immobilization, a problem which possibly has not been considered enough in former studies examining the influence of bed rest on PDPH. Based on the literature and the present findings, we recommend using thin needles with atraumatic tips for spinal anaesthesia if possible. Recumbency presents an avoidable stress for patients as well as medical staff and should no longer be ordered.

Adolescent↗
PubMed1997

[Perfusion changes in hemodilution. The effect of extensive isovolemic hemodilution with gelatin and hydroxyethylstarch solutions on cerebral blood flow velocity and cutaneous microcirculation in humans].

OBJECTIVE: Quantifying the influence of extreme isovolemic hemodilution (NH) with different colloids on cerebral blood flow velocities (transcranial Doppler sonography) and cutaneous microcirculatory blood flow (laser Doppler flowmetry) in healthy, non-premedicated volunteers was the aim of this study. METHODS: In seven volunteers (randomized cross-over design) 20 ml/kg blood was withdrawn within 30 min and simultaneously replaced with 6% hydroxyethyl starch (200,000/0.5, HES) or 3% gelatin (GEL). Thirty minutes later, the autologous blood was retransfused (RT) within 30 min. Due to a severe allergic reaction to gelatin in one volunteer, only 6 GEL-NH were evaluated. Recorded parameters were: mean blood flow velocities (Vm-MCA) as well as the pulsatility index (PI) and the resistance index (RI) over the middle cerebral artery. In addition laser Doppler flux (FLUX), cell velocity (SPEED), mean arterial pressure (MAP), heart rate (HR), hemoglobin (Hb) and hematocrit (Hc) were monitored. RESULTS: NH resulted in a withdrawal volume of 1498 +/- 85 ml (HES) and 1493 +/- 95 ml (GEL), (mean +/- SD) and induced a decrease in hemoglobin from 40.9 to 29.0% (HES) and from 39.8 to 30.0% (GEL). RT increased Hc to 34.2% (HES) and 34.5% (GEL). MAP and HR showed no significant alterations in both groups. Following NH, Vm-MCA rose almost the same way in either case (26% HES), 21% (GEL), but decreased continuously again during RT. After completing RT, only in the HES group Vm-MCA still remained higher than baseline values (14% HES, only 3% GEL). Similar inverse regression lines were found for the two groups between Hc and Vm-MCA: [Vm-MCAHES (cm/s) = -1.27 x Hc + 110.9; r = 0.98, P < 0.001 and Vm-MCAGEL (cm/s) = -1.32 x Hc + 110.9; r = 0.91, P < 0.001]. Furthermore, as a result of NH, FLUX and SPEED increased about 61% and 38% in the HES group and remained on higher values in comparison with starting positions (21% FLUX, 13% SPEED). However, the results in the GEL group were of a different kind: FLUX and SPEED increased stupendously to 291% and 114% combined with NH, but both were reduced by RT on a large scale (39 and 27% below baseline values). Whereas RI showed no group differences, there was a remarkable drop in PI during RT (17% HES, 12% GEL). CONCLUSION: The two plasma expanders studied show a close inverse correlation between the alterations of blood flow velocities in the middle cerebral artery and systemic hemoglobin and hematocrit values. In both groups the change in blood flow velocities is comparable. For the first time the results of relative changes in blood flow velocities following hemodilution and retransfusion in healthy volunteers are described that correspond closely by relative cerebral blood flow alterations found in animal studies as well. Moreover, a non-linear correlation of cutaneous microcirculation was shown by means of HES, but also by GEL. Obviously, there was the GEL group to be responsible for pronounced differences in cutaneous circulation.

Adult↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

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↗
PubMed1997

[Effects of various feeding regimens in multiple trauma patients on septic complications and immune parameters].

OBJECTIVE: The aim of this study was to investigate the incidence of septic complications, the immunological changes by the course of lymphocyte subsets and metabolic parameters on polytraumatised patients when given nutritional support in form of early enteral and total parenteral nutrition. Furthermore, we looked for differences between a standard enteral diet and a diet supplemented with arginine, omega-3-fatty acids, nucleotide, and selenium. METHODS: 30 polytraumatised patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II)-Score > 10 points, who received nutritional support for a minimum of 7 days, were randomised to a "supplemented enteral group" (group 1), an "enteral standard group" (group 2), or a "parenteral group" (group 3). In the first both groups there were early enteral feeding. The patients of group 3 were fed isonitrogenous and isocaloric to group 2. Leucocytes, lymphocytes, CD3(+)-, CD4(+)-, CD3+HLA-DR(+)-, CD8(+)-, CD19(+)-subsets, natural killer-cells (CD56+) and metabolic parameters were measured on days 1, 3, 5, 7. RESULTS: Septic complications occurred in 2 patients in group 1, in 1 patient in group 2 and in 4 patients in group 3. The total number of lymphocytes had an increase on day 7 in group 1 (1420/microliter) and group 2 (1620/microliter) and were higher compared with group 3 (1044/microliter). On day 7 T-cells (CD3+) were 1107/microliter in group 1, 1014/microliter in group 2 and 770/microliter in group 3, T-helper-cells (CD4+) rose on day 7 higher in the enteral fed groups (group 1:746/microliter, group 2:719/microliter) than in group 3 (570/microliter). No significant differences between the groups were seen by CD3+HLA-DR(+)-cells, T-suppressor-cells (CD8+), B-cells (CD19+) and natural killer-cells (CD56). CONCLUSION: Early enteral nutrition seems to stabilise the immunosuppression of polytraumatised patients in an earlier phase. There is a consolidation of the lymphocyte counts, and of T(CD3+)- and T-helper-cells (CD4+). This could be the immunological correlate for the number of septic complications in the enteral fed groups. Therefore polytraumatised patients should be fed rather early enteral than parenteral when possible. In the initial phase after the trauma the way of nutritional support has more importance on the immune system as nutritional contents. So, in this form of studying, there is no advantage of immunonutrition.

APACHE↗