[The effect of aprotinin and tranexamic acid on fibrinolysis and thrombin generation during cardiopulmonary bypass]. / Auswirkung von Aprotinin und Tranexamsäure auf die Fibrinolyse und Thrombinbildung bei extrakorporaler Zirkulation.

OBJECTIVE: Antifibrinolytic drug therapy has proved to be effective in reducing blood loss associated with cardiac surgery and cardiopulmonary bypass (CPB). Concerns remain regarding the risk of enhancing thrombosis. In the present study we investigated the effect of aprotinin (AP) and tranexamic acid (TA) on fibrinolysis and thrombin generation during CPB. METHODS: 60 patients undergoing coronary artery bypass graft surgery were randomised in 3 groups. They received either aprotinin ("high-dose-scheme"), tranexamic acid (2 g/h) or no antifibrinolytic therapy (control group). Collection of blood was performed at 7 pre-, intra- and postoperatively predetermined intervals. Fibrinolytic activity was determined by measuring concentrations of D-dimer, thrombin generation by the measurement of thrombin-antithrombin III complex (TAT). RESULTS: There was no significant increase of D-dimers in the AP or TA group. D-dimer concentration in the control group increased significantly after starting CPB. Comparing with the control group, thrombin generation in the AP group was significant less, while TA group produced significantly higher values. CONCLUSION: After the administration of AP for cardiac surgery we observed reductions in both intraoperative fibrinolysis and thrombin generation. In case of TA suppression of fibrinolytic activity in the absence of concomitant reduction in thrombin generation occurred. These results suggest that TA could potentiate a hypercoagulable state with the risk of thrombosis in the perioperative setting.

[Effects of long-term opioid therapy on psychomotor function in patients with cancer pain or non-malignant pain]. / Aufmerksamkeitsbelastung und Reaktionszeiten unter Opioiddauertherapie. Ein Vergleich mit chronischen Schmerz- patienten und mit Nichtschmerzpatienten.

OBJECTIVES: Despite increasing use of oral opioids in cancer and non cancer pain, little is known about the effects of long-term opioid therapy on psychomotor performance. This study was designed to investigate the effects of long-term opioid analgesia on attention and reaction time in cancer pain and in non-malignant pain. METHODS: Three groups of patients (n=128) were studied: 48 patients on long-term opioid therapy (group O; including 33 patients with cancer pain and 15 patients with chronic non-malignant pain), 30 patients receiving non-opioid analgesic therapy for chronic non-malignant pain (group NO) and a control group (group K) of 50 patients without pain and analgesic therapy. Attention was determined by Brickenkamp's d2-test, continuous reaction time by Schuhfried's method (Wiener Determinationsgerät, Mödling, Austria). In addition, a modified questionnaire developed by Zerssen was used to determine the patient's current mood. Pain, fatigue and anxiety levels were estimated by visual analogue scales. RESULTS: Although no significant difference in attention/concentration could be demonstrated between the three groups, patients taking opioids performed Brickenkamp's test a little worse and also demonstrated a significant decline in this parameter with advancing age. Also, in cancer patients attention/ concentration was more impaired than in non-cancer opioid patients. Auditory and optical reaction times were significantly slower in patients on opioids than in the non-opioid analgesic group and highly significant slower than in the control group, while in the more complex combinations test no such difference could be demonstrated. In addition, a highly significant deterioration in reaction times with increasing age could be demonstrated for opioid patients compared to the other groups, while only a non significant prolongation was found between cancer and non-cancer patients on opioid therapy. CONCLUSIONS: Long-term opioid therapy produces a slight (non significant) impairment of psychomotor performance in patients with cancer pain or non-malignant chronic pain. These effects become significantly more pronounced with increasing age and in patients with cancer pain, indicating a higher susceptibility of the elderly towards opioids. These results indicate that, particularly in older patients receiving long-term opioid for cancer oder non-cancer pain, careful evaluation of their effects on psychomotor function is necessary in order to estimate patient's ability to perform his daily activities. However, since opioid effects were only minimal in the non-elderly other factors like basic disease, opioid dose, physical condition and age seem to be of greater importance than the effects of opioids per se.

[The use of remifentanil in critically ill patients. Clinical findings and early experience]. / Remifentanil zur Analgosedierung von Intensivpatienten. Klinische Anwendung und erste Erfahrungen.

OBJECTIVES: It was the aim of this investigation to report our initial clinical experience on the use of remifentanil in critically ill patients undergoing mechanical ventilation. Additionally, we hypothesized that even under intensive care conditions remifentanil might facilitate a temporally predictable and "programmed" tracheal extubation. METHODS: Remifentanil was used for analgesia and sedation of mechanically ventilated patients who were admitted to the ICU following major noncardiac surgery or who had to be ventilated due to respiratory failure. The infusion was started with 0.15 microg/kg/min and then adapted in steps of 0.05 microg/kg/min according to clinical needs. After admission to the ICU the depth of sedation was adjusted to a Ramsay score level of 4 (sleeping patient, immediately arousable) and then targeted at a level of 2-3 (patient awake, co-operative and tranquil or responding to command only). In case of sufficient pain relief but inadequate sedation patients could receive bolus doses of midazolam (1-3 mg) or an infusion of clonidine (0.5 microg/kg/h), the latter especially in case of shivering or hypertension. Prior to extubation bolus doses of piritramide (3-5 mg) and a non-opioid analgesic (metamizol or propacetamol) could be used for postoperative pain relief. Data are presented as mean+/-SD. RESULTS: A total of 46 patients were studied, aged 62.8+/-15.4 yr with a mean APACHE II score of 19.2 points. The duration of remifentanil infusion ranged up to 78 h with a mean of 9. 8 h. The mean infusion rate was 0.14+/-0.08 microg/kg/min during ongoing analgesia and sedation and 0.10+/-0.08 microg/kg/min immediately before its discontinuance. Additional sedatives were necessary in 63% of all patients. Emergence was rapid in the majority of cases: 67% of all patients could safely be extubated within 15 min after termination of remifentanil, and a total of 87% were extubated within 45 min. A development of tolerance was not observed during the study period. CONCLUSIONS: Remifentanil appeared to be suitable for analgesia and sedation of critically ill patients undergoing mechanical ventilation: Even under intensive care conditions recovery was rapid in the majority of cases, and in two thirds of all patients tracheal extubation was temporally predictable and could be timed within 15 min. These results are best explained by the metabolism and offset of action of remifentanil obviously unaffected in the ICU area. However, for fast emergence the cautious use of additional sedatives is crucial.

[Does intrathecal clonidine prolong the effect of spinal anesthesia with hyperbaric mepivacaine? A randomized double-blind study]. / Verlängert intrathekal injiziertes Clonidin die Wirkung einer Spinalanästhesie mit hyperbarem Mepivacain? Eine randomisierte Doppelblindstudie.

BACKGROUND: Clonidine, an alpha 2-receptor agonist, has been reported to prolong the blocking actions of local anaesthetics. The aim of this study was to investigate the effects of spinally injected clonidine on the duration of spinal anaesthesia by mepivacaine and on the postoperative demand for analgesics. METHODS: Forty-five patients who had transurethral urological surgery under spinal anaesthesia were randomized to 3 groups (n = 15 each) and studied in a double-blind fashion. Group I received 80 mg mepivacaine 4% only, while in group II mepivacaine was combined with 75 micrograms clonidine intraspinally and in group III with 150 micrograms clonidine. Onset time, spread of anaesthesia, duration of sensory and motor blockade, regression of anaesthesia and postoperative demand for analgesics were recorded. In addition heart rate and mean arterial pressure were measured at regular intervals. RESULTS: Clonidine had no effect on the onset time and spread or intensity of spinal anaesthesia. The higher dose of clonidine significantly prolonged the duration of sensory blockade by 50 min and the duration of motor block by 40 min, while 75 micrograms had no significant effect. Heart rate and mean arterial pressure were significantly reduced in both clonidine groups when compared to plain mepivacaine. There was no significant reduction in postoperative analgesic demand. CONCLUSION: While clonidine prolonged sensory analgesia, there was also an undesirable prolongation of motor block postoperatively. In addition, there was a significant and long lasting reduction in heart rate and mean arterial pressure in both clonidine groups. Unfavourably, postoperative demand of analgesics was not reduced by spinal injection of clonidine. Thus, the routine addition of clonidine for spinal anaesthesia with local anaesthetics is not recommended.