[Unexpected cerebral side effects of ranitidine].
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Biomedical subjects
Publications and source records attributed to M Tryba.
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In a prospective, controlled, randomized study of a prophylaxis for stress bleeding, 100 high-risk patients in an intensive care unit received, on a daily basis, 1 g of sucralfate every four hours, an antacid every two hours, or 2 g of cimetidine intravenously. All patients also received 50 mg of pirenzepine by intravenous infusion each day. Gastric pH was determined every eight hours. Bleeding was defined as macroscopically visible bleeding. The intragastric pH was less than 4 significantly more often in patients treated with sucralfate than in patients treated with the other agents, but stress bleeding occurred only in patients treated with cimetidine (n = 2) or antacids (n = 2). In the latter two treatment groups, the probability of bleeding correlated with the incidence of pH values below 4. No side effects of sucralfate therapy were observed. The results indicate that prophylactic treatment of stress bleeding with pirenzepine and sucralfate is at least as effective as combined treatment with pirenzepine and cimetidine or antacids.
Sublingual tablets of buprenorphine (Temgesic sublingual) were given in a controlled trial of 41 patients for 2804 patient-days. With a mean starting dose of 1.09 mg and a final dose of 1.53 mg buprenorphine daily there was a good pain-relieving effect. The interval between doses was six to eight hours. The trial did not reveal any direct pointers as to tolerance or addictiveness after long-term intake of the drug. Because of its effectiveness and good duration of action, as well as the absence of negative long-term effects, the drug can be recommended in the long-term management of cancer pain.
Epidural opiates were administered to 139 patients with pain due to malignant diseases via a chronic indwelling catheter inserted percutaneously. So far, 9,716 days of treatment can be evaluated. In 87% of the patients whose pain previously could not be controlled with conventional analgesic approaches, epidural opiates resulted in remarkable pain relief. With a mean daily dose of 15.6 mg morphine (range 2-290 mg) or 0.86 mg buprenorphine (range 0.15-7.2 mg) half of the patients could be treated as outpatients. The mean duration of therapy was 72 days (range 1-700 days), 26 catheters being in place for more than 100 days and one catheter being in place for 510 days. Two severe side-effects (meningitis) were observed, both patients being free of symptoms after catheter removal and antibiotic therapy. Epidural opiates proved to be a valuable method of pain control in terminal illness. The method should be reserved for those patients, for whom oral opiates fail to produce effective pain relief.
In a prospective controlled clinical study interactions between nondepolarizing muscle relaxants and acylaminopenicillins were investigated electromyographically. Six patients in each group received either apalcillin, azlocillin, mezlocillin or piperacillin during the operation. Muscle relaxation was maintained using the short acting nondepolarizing relaxant vecuronium, which shows no cumulative effect within clinical dosages. The intra-individual comparison with the control period (100%) showed a significant prolongation of the duration of action after a fixed dose of vecuronium. The mean increase was +26% following apalcillin, +46% after piperacillin, +38% following mezlocillin and +55% following azlocillin. The shortest time of the control periods was 8.6 min and the maximum time was 32.6 min. We also found a significant depression of the EMG-response. No significant differences could be detected between the four antibiotics. The method described here has proven to be sensitive enough to detect clinically relevant interactions with muscle relaxants. As a result of our study, caution seems to be necessary if acylaminopenicillins are administered in the early postoperative period.
We present a female patient in whom numerous lumbar punctures for epidural anaesthesia were followed by a delayed development of a large subcutaneous haematoma in the lumbar region. The outcome was fatal. The patient's basic disease was found to be chronic myeloic leukaemia that had caused an excessive elevation of platelet count. We, therefore, suggest that lumbar punctures for epidural anaesthesia should be approached with extreme care in cases of thrombocytaemia. If possible, repeated punctures for the placement of epidural catheters should be avoided.
The authors report a modified positioning of patients for long-term handsurgical operations under regional anaesthesia. After equalizing the level of hand- and operating table, the operating table is tilted 10-15 degrees towards the hand-table. The upper limb is abducted only 30-40 degrees and then rotated outwards. This guarantees a comfortable positioning of the patients for a longer period of time.
The site of action of intravenous regional analgesia is controversial. We developed a new method to investigate if the local anaesthetic primarily blocks the peripheral nerve endings or the main nerve trunks. Intravenous regional analgesia was carried out in six volunteers who received 4 mg/kg prilocaine 1.5%. An additional finger tourniquet was placed at the third finger. While in the other four fingers complete analgesia was observed after five minutes, no adequate analgesia could be detected in the third finger distal of the finger tourniquet. This observation proves that the principal site of action of intravenous regional analgesia is at the peripheral nerve endings. Two further studies, with contrast media and radio isotopes, were carried out to investigate the spread of the injected volume. Both investigations show that the injected volume spreads distally into the fingers.
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Cimetidine 10 mg/kg orally was given at varying times from 60 to 240 minutes pre-operatively to 100 healthy children between the ages of 6 months and 14 years. Cimetidine proved to be most effective when given between 120 and 180 minutes before the induction of anaesthesia. All patients in this group had a gastric pH of more than 2.5 and the mean volume aspirated was also significantly lower than that in the control group. The average peak blood concentration after 10 mg/kg oral cimetidine in four healthy children was 3.25 micrograms/ml (range 1.20-4.80) and occurred 75 minutes after administration (range 60-120 minutes). In these patients the mean (SD) half-life of cimetidine was 138 (18) minutes. The reduction of gastric juice volume and acidity produced by 10 mg/kg oral cimetidine given 120-180 minutes prior to induction of anaesthesia has important clinical implications.
H2-antagonists, antacids and pirenzepine are effective drugs for prophylaxis of stress ulcer bleeding. Combined medication seems to be superior to single medication, but investigations of the effectiveness of a pirenzepine-antacid prophylaxis have not been carried out. We therefore evaluated the effect of this combination on gastric pH and on prevention of stress bleeding in ICU patients. In a prospective controlled randomized study 33 patients in each group received 50 mg. pirenzepine intravenously as a basic medication and alternatively 2000 mg. cimetidine i.v. or 2-hourly 10 ml. antacid. Gastric pH was determined three times per day. Stress bleeding was defined as bloody gastric juice, haematemesis or melaena. Two stress bleedings could be detected in each group. The pirenzepine-antacid combination proved to be superior to ensure a gastric pH of more than 3.5 than the pirenzepine-cimetidine group. After removal of the nasogastric tube the 2-hourly application of antacids proved to be impracticable.
The effect of combined intramuscular premedication with H1 + H2-receptor-antagonists on histamine-induced cardiovascular and cutaneous reactions was studied in 8 volunteers in a randomized placebo-controlled double-blind crossover trial and compared with premedication with H1-receptor antagonist alone and with the histamine-induced effects without premedication. As H1-receptor antagonist the volunteers received 0.5 mg/kg promethazine i.m. 45 min before the start of histamine infusion; as H2-receptor antagonist we used 400 mg cimetidine i.m. 120 min before application of histamine. While the premedication with promethazine alone could prevent histamine-induced tachycardia, fall of blood pressure and cutaneous reactions only partially, these reactions were almost completely prevented by combined premedication. Like intravenous application of H1 + H2-receptor antagonists shortly injected before induction of anesthesia, intramuscular premedication with promethazine and cimetidine can prevent anaphylactoid reactions. In contrast to intravenous application, the latter application is also effective in reducing the risk of acid aspiration syndrome and as a sedative.
In a prospective controlled study 30 parturients provided for elective cesarean section were premedicated either with no specific medication for prophylaxis of aspiration pneumonia or 400 mg cimetidine orally at the evening and 400 mg intramuscularly two hours prior to induction of anesthesia. In the cimetidine treated group only one patient had a gastric pH below 2.5, while in the control group 11 patients had a pH below this limit. The gastric volume in the cimetidine treated group also was significantly reduced. No side effects could be observed in mothers and children. Application of intramuscularly cimetidine seems to be an effective method for prophylaxis of aspiration pneumonia in obstetric anesthesia.
Buprenorphine sublingual tablets (0.2 mg) were investigated in therapy of cancer pain. In 67 patients there was a good analgetic effect in 60%, even in those cases treated with other opiates before. The induction time was quite long (60 min.) but is no problem in chronic administration. Effective pain relief was obtained even in final stages of cancer. The mean daily dose of buprenorphine had been 1.2-1.7 mg, the mean duration of analgesia being 6-8 hours with a single dose of 0.2-1.0 mg buprenorphine. Typical opiate-side-effects were registered and well tolerated after some days' treatment. There was no respiratory depression. Buprenorphine sublingual tablets are certainly a good alternative in orally available opioids.
In a prospective randomized study, 60 outpatients received 0.8%, 1.5% or 2% prilocaine (4 mg/kg body weight) as i.v. regional anaesthesia for operations in the carpal region. The latent period, quality and duration of analgesia after release of the tourniquet were analysed. The latent period was shortest with 2% prilocaine. The duration of analgesia after tourniquet release increased from 5.7 min with 0.8% to 15.6 min with 2% prilocaine. The plasma concentrations after 1.5% prilocaine were significantly less than with 0.8% prilocaine.
In a prospective randomized study, 60 children between 1 and 8 years of age in three groups received no premedication, 10 mg kg-1 cimetidine orally or 40 mg kg-1 cimetidine rectally for prophylaxis of acid aspiration syndrome 120-180 min before induction of anaesthesia. The pH of the stomach contents was above 2.5 in both cimetidine groups. The aspirated gastric volume was significantly reduced with rectal cimetidine compared to the other groups. Rectal cimetidine proved to be the more effective drug for prophylaxis of acid aspiration syndrome in paediatric anaesthesia.
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For an analysis of the risk factors for stress bleeding, 24 risk factors selected from 202 clinical parameters were analysed, and their values determined in 586 medical and surgical intensive-care patients treated for at least six days between 1975 and 1980, who received no prophylactic medication. In 420 patients who received a prophylactic treatment with 800 mg or 1200 mg cimetidine, 2-hourly 30 ml antacids or 30 mg pirenzepine individually or in combination, the total risk scores were determined as the sum of the risk factors. This risk score served as the unit for comparison of the prophylaxis groups. Combined medication with two or three drugs proved to be significantly superior to treatment with either of the medicaments given alone.