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M Tryba

Publications and source records attributed to M Tryba.

At least 55 records · Page 3Linked to original sources

Critical care pharmacotherapy. A review.

During recent years, research in critical care medicine has focused on the role of the gastrointestinal tract in the pathogenesis of multiple organ failure and nosocomial infection, and on preventive measures. Gram-negative bacterial overgrowth of the oropharynx and stomach has been proved to be a cause of nosocomial pneumonia. Topical application of antibiotics into the oropharynx and stomach, and preservation of gastric acidity have been shown to be effective prophylaxis in ventilated patients. Recent studies have demonstrated that gastric alkalinisation is no longer necessary for the prevention of stress ulcer bleeding in critically ill patients. Tissue hypoxaemia, not gastric acidity, is the underlying pathomechanism of stress ulcer bleeding. In experimental investigations, pirenzepine and sucralfate improved gastric mucosal oxygen supply. Both compounds effectively prevent bleeding without increasing gastric pH. In mechanically ventilated patients, significantly lower rates of pneumonia occur with both of these drugs compared with antacids or histamine H2-receptor antagonists. Topical antibiotics (selective digestive decontamination) are most effective in patients with alkaline gastric juice, but of only marginal clinical relevance in those with acidic gastric contents. Isoflurane, propofol and clonidine have been recently investigated for sedation of ventilated patients. Isoflurane may lead to fluoride accumulation after more than 1 day. Propofol dosage has to be increased more often after 4 to 7 days, leading to fat overload and significantly increased costs. Clonidine was highly effective in patients with 'sympathetic overshoot', e.g. those experiencing alcohol or opioid withdrawal. Wound infections are an important problem in burn patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Critical Care↗

Inotropic support of the critically ill patient. A review of the agents.

Intensive care patients often require inotropic support to stabilise circulation and to optimise oxygen supply. In this context, the catecholamines norepinephrine (noradrenaline), epinephrine (adrenaline), dopamine and dobutamine are still the mainstay of therapy. They provide, to different extents, a variety of adrenoceptor-mediated actions comprising vasoconstriction (via alpha-receptors) as well as vasodilatation (via beta 1-receptors), and an increase in cardiac output by enhancing inotropy and heart rate (again via beta 1-receptors). Because of their favourable pharmacokinetic profile (plasma half-lives of about 2 minutes) their actions can easily be controlled. Combinations of different catecholamines with each other or with other drugs such as phosphodiesterase inhibitors or nitrates lead to a broad spectrum of possible haemodynamic actions. However, the use of catecholamines is limited by side effects like tachycardia, hypertension and disturbances of organ perfusion caused by vasoconstriction. Furthermore, as a result of receptor downregulation during long term therapy, the efficacy of catecholamine treatment decreases. These shortfalls stimulated the search for alternatives to catecholamine treatment. Among these, phosphodiesterase inhibitors (e.g. enoximone and amrinone) appear to be the most promising drugs which have been introduced into acute clinical practice up to now. They act via inhibition of the phosphodiesterase isoenzyme III, leading to higher intracellular calcium levels by increasing cyclic adenosine monophosphate (cAMP) levels. These agents improve cardiac performance by enhancing contractility, reducing left ventricular afterload and improve diastolic relaxation. In cases of failing catecholamine therapy due to receptor downregulation, treatment with phosphodiesterase inhibitors may still be effective since their action is not receptor-mediated. Inhibition of the phosphodiesterase enzyme in vascular smooth muscle leads to vasodilatation. Therefore, in low cardiac output states combined with increased total peripheral or pulmonary vascular resistance, phosphodiesterase inhibitor therapy is particularly effective. Depending on the dosage and the speed of intravenous administration, the use of phosphodiesterase inhibitors sometimes results in pronounced decrease of blood pressure which may require vasopressor therapy. Other drugs including histamine H2-agonists are currently under investigation. Their value in the treatment of intensive care patients has still to be evaluated.

Cardiotonic Agents↗

[Does clonidine modify the hypnotic effect of propofol?].

The administration of alpha 2-adrenoceptor agonists before the induction of anaesthesia leads to a significant reduction in the amount of anaesthetic medication required, probably due to an attenuation of haemodynamic stress responses in centrally mediated sympathicolysis. However, it is not yet known whether alpha 2-adrenoceptor agonists influence the hypnotic action of anaesthetics. Therefore, this study was performed to evaluate the influence of the alpha 2-adrenoceptor agonist clonidine on the potency and the duration of the hypnotic action of anaesthetic agents. METHOD. The study was approved by the local ethical committee. To study the effect of clonidine on the potency of propofol we determined the ED50 of propofol with and without clonidine pretreatment. To this end, 100 unpremedicated patients (ASA I or II) were randomly assigned to receive 4 micrograms/kg body weight clonidine or placebo, each of which was dissolved in 100 ml NaCl and infused over a period of 15 min starting 30 min before the induction of anaesthesia. According to the results of a pilot study, patients who had been treated with clonidine received either 0.25, 0.5, 0.75, 1 or 1.25 mg/kg propofol for anaesthesia induction. Patients in the placebo group received 0.5, 1, 1.5, 2 or 2.5 mg/kg propofol. The success of anaesthesia induction was evaluated clinically (eye opening on command, eyelid reflex). On the basis of these data the ED50 of propofol with and without clonidine pretreatment was calculated using the modified probit analysis according to Spearman and Kärber. The effect of clonidine on the duration of anaesthesia was compared in six groups of 10 patients each, who received 1, 1.5 or 2 mg/kg propofol for anaesthesia induction with and without prior clonidine treatment. RESULTS. In the placebo group a dose of 0.5 mg propofol per kg did not produce a hypnotic effect in any patient, while 2.5 mg propofol per kilogram of body weight was effective in all patients. In the clonidine group 0.25 mg propofol per kilogram of body weight had no hypnotic effect, while 1.25 mg propofol per kilogram of body weight was effective in all patients. Increasing the dose of propofol resulted in an increasing number of successful anaesthesia inductions in the placebo as well as in the clonidine group. According to these data, the ED50 of propofol with clonidine was calculated at 0.675 +/- 0.23 mg/kg with clonidine and 1.5 +/- 0.58 mg/kg without clonidine pretreatment. Increasing the dose of propofol did not result in a significant increase in the duration of anaesthesia (1 mg/kg: 260 +/- 114 s; 1.5 mg/kg: 270 +/- 103 s; 2 mg/kg: 295 +/- 152 s). However, premedication with clonidine almost doubled the duration of the hypnotic action of propofol (1 mg/kg: 457 +/- 239 s; 1.5 mg/kg: 501 +/- 249 s; 2 mg/kg: 582 +/- 254 s) (P < 0.01). CONCLUSION. According to these findings the administration of clonidine prior to anaesthesia induction significantly increases the potency and the duration of the hypnotic action of propofol. From our data we conclude that the influence of clonidine on the hypnotic action of anaesthetics is an important factor in the reduction of anaesthetic requirements observed after clonidine pretreatment.

Adrenergic alpha-Agonists↗

[Does the mixture of bupivacaine and prilocaine as opposed to bupivacaine afford a clinical advantage in epidural anesthesia?].

Local anaesthetic mixtures are often used to shorten the onset of regional anaesthesia. However, the results of these mixtures of epidural anaesthesia (EDA) are controversial. Alkalinisation of bupivacaine shortens the onset of EDA. Since mixing prilocaine with bupivacaine results in a local anaesthetic mixture with a pH of 6.8, we investigated whether this mixture can shorten the onset of EDA compared to plain bupivacaine. METHOD. In a randomised, double-blind study, 60 patients received single-shot EDA with a standardised amount of local anaesthetic (1 ml/segment for 150 cm body height +0.1 ml/segment for each further 5 cm). Group A received plain bupivacaine 0.5%, group B bupivacaine 0.5% and prilocaine 2% in a 1:1 ratio. Sensory (loss of warm/cold and pinprick sensation) and motor blockade (modified Bromage score) were studied 5, 10, 15, 20, 30, and 40 min after injection of the local anaesthetic. RESULTS. There was no difference in the onset of sensory blockade: loss of warm/cold and pinprick sensation developed in the same manner in both groups. Ten minutes after injection all patients showed changes in the perception of warm and cold stimuli. In group A this ranged from T 8.1 +/- 2.14 to L 4.36 +/- 1.79 and in group B from T 8.8 +/- 2.0 to L 4.4 +/- 1.55. Forty minutes after injection loss of warm/cold sensation ranged from T 6.6 +/- 2.89 to L 5.4 +/- 1.42 in group B and from T 7.2 +/- 1.24 to L 5.7 +/- 0.88 in group A. Nearly the same results were obtained for the pinprick test. Motor blockade developed more rapidly and intensely in group B. At the end of the observation period there were still 5 patients without any motor blockade in group A, while all patients in group B showed signs of motor blockade. DISCUSSION. Shortening of the onset times has been observed when alkalinized local anaesthetic solutions with a pH above 7.0 are used for EDA. In the present study the mixture of prilocaine and bupivacaine did not shorten the onset of EDA, most likely because the pH of this mixture is only 6.8. In contrast to peripheral nerve blocks, mixtures of local anaesthetics for EDA do not offer a clinical advantage with respect to onset time compared to plain local anaesthetics.

Adolescent↗

[Fentanyl-TTS for postoperative pain therapy. A new alternative?].

Treatment of postoperative pain is often insufficient. It normally consists of systemic application of an analgesic drug or a regional technique of analgesia. Fentanyl-TTS may be a new approach for postoperative pain therapy. Fentanyl is incorporated into a transdermal system; after application to the skin continuous release of therapeutic doses is achieved for a period of 72 h. Serum peak levels are obtained 8-16 h after application; the serum half-life is about 16-21 h because of the dermal depot. Fentanyl-TTS was administered in several clinical studies for therapy of postoperative pain. The efficacy of this new form of application could be demonstrated. For the first 12 h the patients needed supplementary doses of analgesic drugs in the same range as the placebo groups because of the lag time of fentanyl-TTS. In the following 12 h the need for supplementary analgesics was significantly reduced. After removal of the patch, the need for analgesics was still reduced for 12 h. In 21 of 341 patients respiratory depression occurred under therapy with fentanyl-TTS; no respiratory depression was observed in the placebo groups. Thus, respiratory depression might occur in up to 9% of postoperative patients treated with fentanyl-TTS. Other adverse effects were nausea (62%), vomiting (26%), sedation (22%), urinary retention (11%), headache (5%), and dizziness (8%). Local reactions under the patch were erythema (39%) or pruritus (9%). These phenomena disappeared within a few hours. The pharmacokinetics of fentanyl-TTS have two major drawbacks: during the first 12-15 h the patients need supplementary analgesics, usually opioids.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Cutaneous↗

Long-term oral opioid therapy in patients with chronic nonmalignant pain.

In contrast to the use of opioids for the treatment of acute and chronic cancer pain, the administration of chronic opioid therapy for pain not due to malignancy remains controversial. We describe 100 patients who were chronically given opioids for treatment of nonmalignant pain. Most patients experienced neuropathic pain or back pain. We used sustained-release dihydrocodeine, buprenorphine, and sustained-release morphine. Pain reduction was measured with visual analogue scales (VAS), and the Karnofsky Performance Status Scale was used to assess the patient's function. Good pain relief was obtained in 51 patients and partial pain relief was reported by 28 patients. Only 21 patients had no beneficial effect from opioid therapy. There was a close correlation between the sum and the peak VAS values (r = 0.983; p less than 0.0001) and pain reduction was associated with an increase in performance (p less than 0.0001). The most common side effects were constipation and nausea. There were no cases of respiratory depression or addiction to opioids. Our results indicate that opioids can be effective in chronic nonmalignant pain, with side effects that are comparable to those that complicate the treatment of cancer pain.

Adult↗

Conservative treatment of stress ulcer bleeding: a new approach.

Stress ulcer prophylaxis diminishes but does not eliminate the risk of severe bleeding from this complication. In 70-80% of the cases the source of bleeding is hemorrhagic gastritis. No controlled studies exist which have in particular investigated conservative therapy in patients with stress-induced hemorrhage. Even effective measures to suppress gastric acid secretion or to reduce splanchnic blood flow are ineffective in 10-40% of intensive care unit patients with stress-induced bleeding. In these cases total gastrectomy has so far often been the only therapeutic approach. We report our experience with a new approach in treating severe stress-induced hemorrhagic gastritis after ineffective primary treatment with H2-receptor antagonists, pirenzepine and somatostatin. Continuous gastric lavage with 5-10 l ice-cold Ringer's solution was used until complete cessation of bleeding, as evident from clear lavage. Repeated administration of 12 g sucralfate (60 ml) at 2-h intervals for 24 h through a gastric tube was used to prevent recurrence of bleeding and to promote healing. Sucralfate was reduced on the 2nd and 3rd day to 20 ml 2-hourly and later to 10 ml 4-hourly. In four patients this treatment was used as an ultima ratio when the patients were already scheduled for total gastrectomy. A total of 23 patients were treated during a 7-year period; all of them responded successfully, and no patient required surgery.

Adult↗

The gastropulmonary route of infection--fact or fiction?

Published studies relating to whether medicinal stress-bleeding prophylaxis leading to an increase of gastric pH favors the development of bronchopulmonary infections are reviewed. Results from studies in healthy humans, patients with ulcer disease, and patients in the intensive care unit (ICU) clearly show that the risk of gastric bacterial colonization significantly increases relative to increasing gastric pH. Moreover, a drug-induced increase of gastric pH leads directly to gastric bacterial colonization also in patients in the ICU, above all with bacteria typical of the gastrointestinal tract. Comparing the different bacterial spectra of the oropharynx, stomach, and upper small intestine, it becomes clear that the stomach is a reservoir of bacteria independent of the oropharynx and also subject to retrograde colonization due to the duodenogastric reflux. Both by means of microbiological and in particular direct detection procedures, it can be demonstrated that in at least 30-40% of intubated patients a gastropulmonary route of colonization occurs. In patient groups without a medication-induced increase of gastric pH the number of bacteria detected in the tracheal secretion is about 33% less than in the case of conventional stress-bleeding prophylaxis. These findings make it understandable that a highly significant increase in the pneumonia rate is seen in patients receiving pH-increasing stress-bleeding prophylaxis versus control groups without therapy essentially influencing gastric pH. A risk score was developed that allows an easy description of those patients who are at an increased risk of pulmonary infections due to the gastropulmonary route of colonization.

Anti-Ulcer Agents↗

[What benefit and harm can be expected from screening and routine examinations and from their omission?].

Benefit and harm of screening and routine tests or their omission are dealt with in four parts. In the first part methods are described to evaluate the diagnostic value of medical testing. The concepts of diagnostic sensitivity, diagnostic specificity, and pre- and posttest probability of a diagnosis are defined. It is then shown how these concepts intercorrelate and how their numerical values can be calculated ("Bayes" theorem"). In consideration of the above mentioned intercorrelations, the second and third parts deal with the diagnostic value of preoperative routine tests from an anaesthesiological viewpoint, and the diagnostic value of other screening and follow-up tests is discussed from a gynaecological point of view. Pre-operative laboratory tests are necessary, and necessary only then, if careful evaluation of patient history and physical examination reveal pathological findings or risk factors. The benefits from regular lab-screening tests and follow-up tests, as recommended to the gynaecologists, are low. This is due to the large share of "healthy" women among the gynaecological patients, as well as the fact that treatment of early detected recurrences shows no demonstrable advantage over treatment of later detected recurrences. In the fourth part, we show that no adverse forensic consequences are to be expected if diagnostic tests are omitted because of demonstrably low diagnostic value. In case of legal procedures against the physician, a medical expert will have to evaluate the diagnostic value of the omitted test objectively from an "ex-ante" point of view, using the methods defined in the first part.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential↗

Sucralfate versus antacids or H2-antagonists for stress ulcer prophylaxis: a meta-analysis on efficacy and pneumonia rate.

OBJECTIVES AND METHODS: Histamine2 (H2)-receptor antagonists and antacids have been the basic drugs for the prevention of stress bleeding in ICU patients during the past decade. Recently, drugs without major influence on gastric pH have been investigated in stress bleeding prophylaxis. Therefore, a meta-analysis (Mantel-Haenszel test) was undertaken to determine the efficacy of sucralfate in the prevention of macroscopically visible stress bleeding, as well as the influence of sucralfate on the frequency of pulmonary infections. RESULTS: The efficacy of sucralfate was compared with H2-antagonists in nine studies and with antacids in eight studies. Sucralfate was significantly more effective than H2-antagonists (typical odds ratio 0.532, 95% confidence interval 0.303 to 0.933) and equally as effective as antacids (typical odds ratio 0.868, 95% confidence interval 0.452 to 1.667). The pneumonia rates of those patients who were administered sucralfate were compared with the rates of those patients who were given H2-antagonists in five studies and with those patients who were given antacids in four studies. Pneumonia was a significantly more frequent occurrence under prophylaxis with H2-antagonists (typical odds ratio 0.498, 95% confidence interval 0.316 to 0.783) as well as with antacids (typical odds ratio 0.402, 95% confidence interval 0.235 to 0.687). CONCLUSION: Sucralfate is an effective drug for the prevention of stress bleeding that minimizes the risk of nosocomial pneumonia in long-term ventilated ICU patients.

Antacids↗

[Histamine release and cardiovascular reactions to implantation of bone cement during total hip replacement].

Cardiovascular reactions to acrylic bone cement in patients with total hip replacement are a common complication. Hypotension and arrhythmias are the most frequently observed symptoms. Elderly patients with fractures of the femoral neck constitute a special risk group. In some patients these reactions can be fatal. The mechanisms suggested to explain these reactions are embolism of air, polymer or fat, reaction to the heat, and toxic or vasodilating effects of the acrylic monomer. In a pilot study and in a case report a significant rise of the plasma histamine was described following cementation of the femur. We therefore performed an investigation to find whether application of bone cement to the femur caused histamine release in elective hip surgery, and, independently of this, also investigated whether premedication with H1- + H2-antagonists had any effect on the cardiovascular reactions due to bone cement implantation into the femoral shaft in elderly patients with hip fracture. METHODS. Part I. In all, 40 patients, scheduled for elective surgical hip replacement were anesthetized by general or epidural anesthesia. Patients were continuously monitored by ECG. Blood pressure was recorded noninvasively at 2-min intervals during the study. Blood samples for the determination of the plasma histamine were taken immediately before implantation of the bone cement into the femur, and 2, 5, and 10 min after. Part II. A further group of 20 patients aged greater than or equal to 70 years with fractures of the femoral neck and in whom total hip replacement was planned were included in the study. In this group, 10 patients were randomly assigned to receive 4 mg clemastine + 400 mg cimetidine i.v. about 15 min before implantation of the bone cement. All patients were operated on under general anesthesia. ECG was monitored continuously and blood pressure was monitored at 2-min intervals during the study. Changes of the blood pressure and heart rate and therapeutic interventions following the implantation of the bone cement were documented. RESULTS. Part I. In 11 of the 40 patients (27.5%) plasma histamine increased by greater than 0.5 ng/ml (9 patients greater than 1 ng/ml). In comparable groups (patients with a control systolic blood pressure less than or equal to 130 mmHg) the histamine responders showed a significantly greater reduction in systolic blood pressure (-5.7 +/- 14.7 vs -17.7 +/- 8.6 mmHg). Part II. In the control group we observed a significantly greater fall in systolic blood pressure than in premedicated patients (41.5 +/- 25.4 vs 11.0 +/- 13.4 mmHg). In the control group 7 of the 10 patients required therapeutic interventions, while in the premedicated group only one therapeutic intervention was necessary (P less than 0.05). DISCUSSION. We have demonstrated that the implantation of acrylic bone cement into the femur may increase plasma histamine by greater than 1 ng/ml. In elderly patients with preexisting cardiac diseases or/and hypovolemia even moderate histamine release can cause serious, sometimes potentially fatal, cardiovascular complications. In this special risk group with hip fractures we found a significant reduction in the frequency of cardiovascular reactions to bone cement implantation in patients premedicated with H1 + H2 antagonists. Because we also observed significant falls in systolic blood pressure in premedicated patients, we assume that the pathogenesis of cardiovascular reactions to bone cement implantation is multifactorial. It may be that potentially lethal complications only occur if two or more of the predisposing factors (hypovolemia, myocardial insufficiency, arrhythmia, embolism, histamine release) are present simultaneously. Pre- and intraoperative measures therefore have to be instituted to eliminate all possible risk factors.

Aged↗

[Rational prevention of stress hemorrhage--effectiveness, side effects, costs].

Stress ulcer bleeding occurs in special risk groups. The main cause of this complication is the loss of protective mechanisms of the gastric mucosa. Preventive measures aim to strengthen the protective mechanisms or to lower the aggressive factors, mainly the gastric acid. Meta-analysis demonstrates that drugs that enhance the protective mechanisms are superior to a regimen that only reduces the secretion of gastric acid. The most important side effects of stress ulcer prophylaxis are related to the inhibition of gastric acid, the blockade of the cytochrome P450 system and the blockade of central and cardiac H2 receptors. Handling difficulties most often occur during treatment with antacids. The costs of prophylaxis are lowest for sucralfate. Rational decision analysis shows that pirenzepine given as parenteral medication and sucralfate as enteral medication are the most suitable drugs for stress ulcer prophylaxis.

Anti-Ulcer Agents↗