[Anesthesia in patients with cardiovascular diseases. 1. General and specific aspects of coronary heart disease and arterial hypertension].
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Biomedical subjects
Publications and source records attributed to R Hering.
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OBJECTIVE: To evaluate the efficacy and safety of dihydroergotamine (DHE) nasal spray in patients suffering from common or classical migraine. METHODS: In a double-blind parallel-group study, 52 outpatients with migraine were randomly allocated to DHE nasal spray or to placebo. Two puffs, one in each nostril, was taken as an initial dose (resulting in either 0.5 or 1 mg of DHE), followed by another puff (0.5 mg) after 30 and 60 minutes, if necessary, achieving a maximum dose of 2 mg for patients of the DHE 1-mg group or of 1.5 mg for patients of the 0.5-mg group. Four consecutive attacks were thus treated. The efficacy analysis was done for observed cases. The main outcome measure was reduction of the severity of the attacks. RESULTS: No differences were observed in the migraine characteristics or the number of treatments of the patients from the different groups. Dihydroergotamine 1 mg tended to provide better relief than 0.5 mg, although the effect was not statistically significant. Patients taking DHE used less rescue medications, with a dose-dependent effect. Side effects were reported by four patients receiving DHE but not placebo. The tolerability of the drug was assessed as good by 94% of the patients. CONCLUSION: These findings suggest that DHE nasal spray is well tolerated and has dose-dependent efficacy in migraine.
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Lithium is widely used in the prophylaxis of episodic cluster headache without formal evidence of efficacy. Placebo-controlled clinical trials are not easy in conditions characterized by frequent severe pain. In this study, it was assumed that lithium would work quickly if at all, and placebo response would be zero. Strict diagnostic criteria excluded uncertain or atypical cases. Patients were male in so-far untreated episodes expected to last for at least 3 weeks more. In a double-blind, placebo-controlled comparison of matched parallel groups, treatment was either slow-release lithium carbonate, 800 mg/day, or placebo. After 7 days, compliance was estimated by tablet count, blood was taken for lithium assay, efficacy was assessed (attacks stopped or substantially improved) and adverse reactions were recorded. The study was stopped after planned sequential analysis of the 27th patient (13 on lithium, 14 on placebo). Estimated compliance was usually but not always good. Plasma lithium levels were mostly in the range 0.5-0.6 mmol/l on lithium, zero on placebo. Cessation of attacks within 1 week occurred in two patients in each group, substantial improvement in 6/14 (43%) on placebo, 8/13 (62%; NS) on lithium. Only minor adverse events were reported. Lithium treatment was therefore associated with a useful subjective improvement rate but the assumptions made at outset had proved wrong. The trial was stopped because superiority over placebo could not be demonstrated. There were lessons for future trials.
UNLABELLED: The purpose of our study was to find out whether patient-controlled epidural administration (PCEA) of a mixture containing a low-dose local anaesthetic, opioid and alpha 2-agonist provides as good or better postoperative analgesia as continuous epidural administration of the same analgetic solution. METHODS: 30 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into 2 groups. 90 minutes after induction of general anaesthesia all patients received a continuous epidural infusion of 5 ml/h of the analgetic solution (50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine) until the end of surgery. Immediately postoperatively the patients of group A received a continuous infusion of the study solution (5-8 ml/h), the patients of group B received a baseline continuous epidural infusion (3 ml/h), additionally they could self-administer 5 ml boli via a PCEA device. Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side effects within the first 24 hours postoperatively. A standardised interview on analgesia and side effects was held 2 days after surgery. RESULTS: The PCEA group demanded less epidural analgesics (gr. B: 112 +/- 33 ml vs. gr. A: 135 +/- 20 ml) p < 0.01). Both continuous epidural infusion and patient-controlled administration provided very good analgesia at rest (gr. A: VAS 0.4 +/- 0.4 and gr. B: VAS 0.4 +/- 0.5) (n.s.). On exercise continuous epidural infusion of analgesics resulted in significantly lower pain scores (gr. A: 1.9 +/- 1.1) than patient-controlled application (gr. B: 3.4 +/- 1.1) (p < 0.01). We did not notice severe side effects such as respiratory depression or drop of heart rate or blood pressure. CONCLUSION: In patients at rest both continuous and patient-controlled epidural administration of analgesics provides excellent analgesia after major abdominal surgery. Contrariwise, patients on exercise who could use a PCA-device experienced more pain compared to those with a continuous epidural infusion technique. On the other hand the patients of the PCA-group consumed less epidural analgesics. We did not notice any severe side effects such as respiratory depression or cardiovascular instability during the study.
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OBJECTIVE: The purpose of this study was to investigate whether continuous epidural administration of combined low dose local anaesthetic, opioid and clonidine can provide sufficient postoperative analgesia after major abdominal surgery. METHODS: 45 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into three groups. Prior to surgery all patients received an epidural catheter before induction of general anaesthesia. After 90 minutes a 10 ml bolus of the study solution was given via the epidural catheter followed by a continuous infusion of 5 ml/h until the end of surgery and further on 5-8 ml/h for 24 hours postoperatively. The solutions consisted of 50 micrograms sufentanil in 50 ml 0.125% bupivacaine (group 1), 150 micrograms clonidine in 50 ml 0.125% bupivacaine (group 2) and 50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine (group 3). Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side-effects within the first 24 hours postoperatively. A standardised interview on analgesia and side-effects was held two days after surgery. RESULTS: At rest excellent analgesia could be provided by all of the tested drug solutions. On exercise we evaluated lower pain scores in group 3 (1.9 +/- 1.1) compared to group 1 (2.8 +/- 1.6) or group 2 (3.8 +/- 2.1) (2 vs 3 p < 0.05). Severe side effects such as respiratory depression or drop of heart rate or blood pressure did not occur. CONCLUSIONS: Epidural administration of drug solutions containing a low dose local anaesthetic, opioid and alpha 2-agonist, provides excellent analgesia after major abdominal surgery. Patients at rest can be treated very effectively with both a combination of only two or with all of the tested drugs. On exercise the mixture containing all analgesics was more efficient than the solutions with only two of the tested drugs. Severe side effects such as respiratory depression or cardiovascular instability were not seen.
The Geschwind-Behan hypothesis, that migraine is more common among left-handed patients, was tested in 320 migraine sufferers. The frequency of left-handedness was also assessed in 68 tension headache patients and compared to that in 140 healthy controls. No significant differences were observed. This study failed to support the association between migraine, tension headache and left-handedness using the IHS classification of headache.
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Data are presented on nine patients with migraine by IHS criteria, recruited from those presenting to the clinic for treatment and needing prophylaxis. Pizotifen 0.5 mg tds was prescribed for 8 weeks and dispensed in special containers with an electronic event recorded concealed in the lid. This responded to the pressure change with each opening of the container and recorded it in real time. The information was later downloaded to a PC for analysis. At trial end, two patients had been lost to follow-up, one had not started the treatment at all, two had dropped out because of alleged side effects (drowsiness), and four patients had completed the study. For these, the quantity of tablets used as a percentage of that prescribed (i.e., compliance assessed on the basis of returned-tablet count) ranged from 62.6% to 91.9%; the percentage of days in which three doses had been taken ranged from only 15.8% to 79%; the percentage of doses taken on schedule (8 h +/- 25% after the previous dose) ranged from 21.1% to 47.3%. It is possible that all evaluations of efficacy and tolerance of migraine prophylactics reported so far have been unsoundly based.
Ergotamine and analgesic misuse are now recognized as causes of chronic daily headache and the condition responds well to drug withdrawal with reduced headache frequency. In this study, we have investigated whether medication misuse is associated with an alteration in membrane transduction which is sensitive to drug withdrawal. This was carried out by assay of the thrombin-stimulated generation of inositol phosphates in platelets from 12 migraine patients with chronic daily headache and analgesic misuse, 7 migraine patients with chronic daily headache and ergotamine misuse and 7 control subjects. After drug withdrawal, a significant decrease in headache frequency was seen at one month in both patient groups. Withdrawal of analgesics produced a significant decrease in thrombin-stimulated inositol phosphate production at one month; this was further decreased a month later with a reduction in Bmax of 60% and no significant change in KD. A similar pattern was obtained in ergot misuse patients, with the KD value decreasing by 56% one month after drug withdrawal. These results provide evidence of an adaptation in transduction with misuse of analgesics and ergotamine which correlates with headache frequency.
Whole blood 5HT levels were measured in seven female migraine sufferers with chronic daily headache due to medication abuse, before and after abrupt medication withdrawal. A statistically significant increase in 5HT levels, from mean 4.89 mumol/l to mean 6.59 mumol/l (p < 0.05, Wilcoxon signed rank test), occurred after 4 weeks of withdrawal. We conclude from this pilot study that 5HT may be important in the physiopathogenesis of chronic daily headache. Alternatively, reduced 5HT may be the result of chronic daily headache or else an epiphenomenon.
We studied vestibulo-ocular reflex measurements in a group of 12 patients suffering from migraine without aura and evaluated the effect of sodium valproate given as prophylactic migraine therapy. The study was randomized, double blind and placebo controlled, with a crossover design. The horizontal vestibulo-ocular reflex was evaluated by the Sinusoidal Harmonic Acceleration test at 0.01, 0.02, 0.04, 0.08 and 0.16 Hz using a computerized rotatory chair system. No abnormalities were found for the vestibulo-ocular reflex gain, phase and asymmetry at each of the frequencies examined during the placebo treatment. These normal vestibulo-ocular reflex measurements contrasted with the repeated complaints of dizziness, vertigo and unsteadiness reported by 7 patients (58%). Sodium valproate affected neither vestibulo-ocular responses nor vestibular complaints but was effective in reducing migraine attacks in 8 of the 12 patients. These results demonstrate that the low frequency vestibulo-ocular reflex measurements are normal in patients suffering from migraine without aura.
Cyclic AMP (CAMP) accumulation induced by isoproterenol (IP) and forskolin in intact lymphocytes was determined in 12 patients with migraine and 12 healthy controls. Our data showed that IP CAMP accumulation (8.20 + 1.08 Pmol/million cells) was significantly (P = 0.033) lower than accumulation in the controls (14.39 + 2.44 Pmol/million cells). Forskolin-induced CAMP did not differ in the two groups. These findings support the association of migraine and a reduced lymphocyte beta-adrenergic receptor sensitivity. An alteration in lymphocyte beta-adrenergic receptor may reflect similar changes in central beta-adrenergic function and may be used as a probe to evaluate its activity.