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Biomedical subjects

H G Kress

Publications and source records attributed to H G Kress.

At least 19 recordsLinked to original sources

[Importance of intrathecal pain therapy].

Intraspinal drug infusion using implantable pumps and catheter systems is a safe and effective therapy for selected pain patients with severe chronic pain. It improves pain relief, reduces drug-related side effects, decreases the need for oral analgesia and enhances quality of life in a segment of chronic pain patients whose pain has not been controlled with more conservative therapies. Intrathecal drug therapy has therefore established its role in the treatment of malignant pain, benign pain and severe spasticity.Careful patient selection and management as well as a multidisciplinary approach are determinants of successful treatment. Current practices for patient selection and management, screening, drug selection, dosing and implantation for intrathecal drug delivery systems are discussed.

Analgesia, Epidural↗

Long-term intrathecal S(+)-ketamine in a patient with cancer-related neuropathic pain.

Neuropathic pain sometimes needs invasive pain therapy. We present the case of a patient with cancer-related neuropathic pain untreatable with conventional pain therapy after tumour-embolization. The patient was treated successfully with intrathecal (i.t.) administration of S(+)-ketamine, in addition to morphine. Plasma concentrations of S(+)-ketamine were measured regularly throughout the treatment. Continuous i.t. administration of S(+)-ketamine over a period of 3 months demonstrated low plasma levels and no unwanted side-effects.

Analgesics↗

[Use of the World Health Organization guidelines on cancer pain relief before referral to a specialized pain service].

In 1986 the World Health Organization (WHO) released guidelines for cancer pain relief. Since then, several controlled studies on effectiveness and practicability of these guidelines have been published. Various authors described inadequate use of these guidelines. We analysed, whether the pain medication of 160 cancer patients referred to the anesthesiological pain clinic at the university hospital of Vienna corresponded to the WHO guidelines or not. Adequacy of pain treatment was assessed using the pain management index (PMI). Multiple criteria were chosen to assess the conformity of the treatment with the guidelines. Furthermore we studied the effect of a strict use of the WHO guidelines in these patients. The average pain intensity of the referred patients was 75 mm (VAS). Negative PMI scores, indicating inadequate pain therapy, were found in 39 % of cases. A violation of the rules was found in 38% of the therapy schedules. Pain medication was then modified by switching to fixed time intervals, escalation of the steps of the WHO ladder, increasing the dosage or treating neuropathic pain with adjuvant drugs. Two weeks later the average pain score of the patients was reduced to 27 mm (VAS). At that time 72% of the patients quoted an adequate reduction of pain. Inadequate knowledge or disregard of the WHO guidelines for cancer pain relief are common and result in unnecessary and prolonged suffering in these patients.

Female↗

[Cannabinoids and the immune system. Of men, mice and cells].

The medical use of cannabis or cannabinoid compounds is controversial. Cannabinoids like the Delta(9)-THC (tetrahydrocannabinol) or the synthetic derivative Nabilone are available against cancer- and HIV-associated cachexia, nausea and vomiting. Over the last 20 years, the cannabinoid receptors CB(1) and CB(2) and their endogenous ligands have been found. The involvement of this endogenous cannabinoid signalling system in feeding, appetite, pain perception and immunomodulation could be demonstrated using animal and in vitro studies. Thus, the concern about immunosuppressive effects in humans using medical cannabinoid preparations grew. However, up to now most human studies have failed to demonstrate a well-defined and reproducible immunosuppressive cannabinoid-effect. Only the smoking of marijuana showed a significant local immunosuppression of the bactericidal activity of human alveolar macrophages. In animal studies, cannabinoids were identified as potent modulators of cytokine production, causing a shift from Th1 to Th2 cytokines. In consequence, a compromised cellular immunity was observed in these animals, resulting in enhanced tumor growth and reduced immunity to viral infections. In vitro, immunosuppressive effects were shown in all immune cells, but only at high micromolar cannabinoid concentrations not reached under normal clinical conditions. In conclusion, there is no evidence that cannabinoids induce a serious, relevant immunosuppression in humans, with the exception of marijuana-smoking which may affect local broncho-alveolar immunity.

Animals↗

Target-controlled infusion of propofol for fibreoptic intubation.

BACKGROUND AND OBJECTIVE: In a retrospective study, we examined the suitability of a departmental clinical protocol for anaesthesia induction with target-controlled infusion of propofol developed for fibreoptic intubation in spontaneously breathing patients scheduled for outpatient oral surgery at the dental clinic of the Vienna University Hospital. METHODS: Propofol was administered using target-controlled infusion (Diprifusor) at increasing target plasma concentrations starting at 2.5 microg mL(-1). After 10 min, an intravenous dose of alfentanil (5-10 microg kg(-1)) was given for pain reduction. After a further 2 min, the patient was evaluated for response to auditory stimulation. If unresponsive, fibreoptic intubation was performed, otherwise the target concentration was increased by 0.2 microg mL(-1) every 2 min until non-responsiveness was attained. RESULTS: Tracheal intubation was successful in all patients without any haemodynamic instability. However, one patient required facemask ventilation for 2 min. No patient was aware of intubation. The plasma concentration required for non-responsiveness was 2.8 +/- 0.4 microg mL(-1) (mean +/- SD). CONCLUSIONS: When using a target-controlled infusion of propofol, fibreoptic intubation can be performed with complete amnesia of the procedure for the patient. However, assisted ventilation of the lungs may be necessary as spontaneous ventilation may cease.

Adult↗

Neuromuscular block and relative concentrations of mivacurium isomers under isoflurane versus propofol anaesthesia.

BACKGROUND AND OBJECTIVE: The augmentation of the effect of neuromuscular blocking drugs with volatile anaesthetics is well documented, but the mechanism remains unclear. The pharmacological interaction and relative plasma concentrations of mivacurium isomers were investigated during either propofol- or isoflurane-maintained anaesthesia. METHODS: Forty-four patients were randomly assigned to one of two groups: isoflurane or propofol. All patients received an initial dose of mivacurium 0.1 mg kg(-1). After recovery of the first twitch (T1) response measured by acceleromyography to 5%, a T1 depression of 90-99% was maintained by infusion. After a steady state was reached, blood samples were taken after 10 and 30 min for analysis of mivacurium isomers. Recovery times for T1 to 251/50/75/90% (TW25-90), train-of-four ratio 25/70% and recovery index (time TW25-75) were recorded after stop of infusion. RESULTS: In the isoflurane group, lower infusion rates were needed (3.0 +/- 1.6 versus 3.6 +/- 1.6 microg kg(-1) min(-1)) and there was a slower recovery (significant for train-of-four ratio 70%: 21.9 versus 17.9 min). The plasma concentrations of mivacurium and its trans-trans isomer (in percentage of the total) were significantly higher in the isoflurane group (10 min: 52.6 versus 25.8%; 30 min: 49.6 versus 23.2%). CONCLUSIONS: For mivacurium, the phenomenon of 'potentiation' of the effect of muscle relaxants by volatile anaesthetics could be due to an increase in the plasma concentration of the potent trans-trans isomer.

Adult↗

Comparison of different quantitative sensory testing methods during remifentanil infusion in volunteers.

BACKGROUND: The aim of this study was to compare thermal and current sensory testing stimuli with respect to opioid responsiveness. METHODS: Eighteen healthy volunteers were randomized in a placebo-controlled, double-blind crossover study to receive an infusion of remifentanil 0.08 micro g kg(-1) min(-1) or saline for 40 min. Test procedures included determination of pain perception thresholds (PPT) and pain tolerance thresholds (PTT) to heat, cold, and current at 5, 250 and 2000 Hz, at baseline and at the end of the infusion. RESULTS: Both current at 5 Hz (PPT 3.69 (SD 2.48) mA vs 2.01 (1.52) mA; PTT 6.42 (2.79) mA vs 3.63 (2.31) mA; P<0.001) and 250 Hz (PPT 4.31 (2.42) mA vs 2.89 (1.57) mA; PTT 7.08 (2.68) mA vs 4.81 (2.42) mA; P<0.001) and heat (PPT 47.4 (2.7) degrees C vs 45.2 (3) degrees C; PTT 51.1 (1.8) degrees C vs 49.7 (1.8) degrees C; P<0.05) detected a significant analgesic effect of remifentanil compared with placebo. No analgesic effect was shown on cold or current at 2000 Hz. The magnitude of responsiveness of current stimuli at 5 Hz and 250 Hz was superior to heat stimuli. CONCLUSION: Both current (5 and 250 Hz) and heat sensory testing detected a significant analgesic effect of a remifentanil infusion compared with saline. There was more response to current testing.

Adult↗

[Gabapentin in the treatment of chronic intractable pain].

INTRODUCTION: Gabapentin has been shown to reduce pain associated with diabetic neuropathia and postherpetic neuralgia. To date it is not known, whether gabapentin is generally effective in other types of pain. It was therefore the aim to study gabapentin in patients suffering from intractable pain with respect to efficacy, predictive factors and side effects. METHODS: Retrospective analysis of the data sheet of pretreated patients suffering from intractable pain and treated with gabapentin as a third line drug at a university pain clinic. Pain intensity (visual analogue scale, VAS 0 -10 cm), pain characteristics, diagnosis, pre- and co-treatment, and side effects were assessed. Response to treatment was defined as a 50% reduction in pain or a pain intensity of VAS </= 3. RESULTS: 99 patients were included. Approximately half the patients (n = 49) responded to gabapentin. Patients suffering from neuropathic pain showed a higher response rate (60%) compared to patients with muscle-sceletal pain (35%). Allodynia was twice as high in the responders (35%) compared to the non-responders (18%) before treatment. No serious side effects were reported. CONCLUSION: Gabapentin was effective in approximately 50% of pretreated patients with intractable pain. Neuropathic pain responded better than pain of other origine. Allodynia may be a predictive factor for a positive treatment effect.

Acetates↗

Does ester hydrolysis change the in vitro degradation rate of cisatracurium and atracurium?

BACKGROUND: We assessed the role of ester hydrolysis as an additional degradation mechanism to Hofmann elimination in the breakdown of cisatracurium and atracurium. METHODS: Cisatracurium and atracurium were incubated in phosphate buffer (pH 7.4, 37 degrees C) with and without the addition of carboxylesterase. Control measurements with an added esterase inhibitor were performed separately. Cisatracurium/atracurium and their degradation products, laudanosine and monoquaternary acid, were analysed using high-pressure liquid chromatography. RESULTS: Degradation of cisatracurium and atracurium proceeded exponentially, and after addition of carboxylesterase, no significant differences in the degradation rates were found. Neither an increase in carboxylesterase activity nor the addition of esterase inhibitor showed any effect. However, areas under the peaks of the chromatogram representing monoquaternary acid increased during incubation with esterase. CONCLUSION: The rate-limiting step in the degradation of cisatracurium/atracurium is Hofmann elimination. Ester hydrolysis is involved in the second degradation step that forms monoquaternary acid, but its contribution to the total elimination rate is negligible.

Atracurium↗

Evaluation of long-term efficacy and safety of transdermal fentanyl in the treatment of chronic noncancer pain.

The objective of this international, multicenter, open-label trial was to assess the efficacy and safety of up to 12 months of therapy with transdermal therapeutic system (TTS) fentanyl in patients (n = 532) with chronic noncancer pain. The trial was completed by 301 (57%) of the patients. The main outcome measures were pain control assessment, global treatment satisfaction, patient preference for TTS fentanyl, and quality of life. The mean dose of transdermal fentanyl (TDF) increased from 48 to 90 microg/h during a period of 12 months. During treatment, on average 67% of patients within the efficacy analysis group (n = 524) reported very good, good, or moderate pain control. Global satisfaction (very good or good) was also stable at 42%. The majority (86%) of patients reported a preference for TDF over their previous treatment (P < .001, binomial test). Short Form 36 quality-of-life scores improved from baseline for bodily pain. The most frequent treatment-related adverse events were nausea (31%), constipation (19%), and somnolence (18%). With regard to opioid-specific adverse events (respiratory depression [< 1%], adrenal insufficiency [< 1%], drug abuse/dependence [1%], and opioid withdrawal syndrome [3%]), these were extremely rare and, with the exception of opioid withdrawal syndrome, none was considered definitively related to the treatment. Long-term treatment with TDF provided a stable degree of pain control in the majority of patients with moderate to severe chronic noncancer pain. It was preferred by the majority of patients compared with their previous opioid medication. Overall, long-term treatment with TDF was generally well tolerated, particularly in view of the low incidence of potentially serious side effects such as drug abuse/dependence and respiratory depression. However, at present, it is important that patients receiving TDF should still be subject to careful assessment and monitoring.

Journal Article↗

The effect of remifentanil on the heat pain threshold in volunteers.

Remifentanil offers a wide range of clinical uses and has been successfully combined with general anesthetics. However, there are few human experimental studies demonstrating the analgesic property of remifentanil. It was our aim to determine the analgesic effect of remifentanil with regard to dose-dependent increments in a human model of heat pain threshold assessment. Twenty healthy volunteers were randomized in a double-blinded cross-over design to receive an infusion of remifentanil or saline. The stepped infusion was increased every 5 min by 0.01 microg. kg(-1). min(-1) up to 0.17 microg. kg(-1). min(-1)and terminated in case of defined safety limits. Thermal sensory testing of the heat pain threshold was performed every 5 min at the left forearm. The dose-response relationship and the effective dose for at least 50% of the subjects (ED(50)) were determined. Remifentanil led to a clear dose-dependent increase of the heat pain threshold differing significantly from placebo (P < 0.0007). The ED(50) of remifentanil equals 0.05 microg. kg(-1). min(-1) (first quartile 0.025 microg. kg(-1). min(-1) and third quartile 0.06 microg. kg(-1). min(-1)) in this experimental setting. In conclusion, an opioid-mediated analgesic effect of remifentanil was determined in a human heat pain threshold model. The dose of 0.05 microg. kg(-1). min(-1) is an effective and safe increment in healthy volunteers.

Adult↗

The long-term antinociceptive effect of intrathecal S(+)-ketamine in a patient with established morphine tolerance.

IMPLICATIONS: Our report describes for the first time the continuous long-term intrathecal application of S(+)-ketamine in a patient with chronic pain and morphine tolerance. Intrathecally applied S(+)-ketamine led to a significant pain reduction and consecutively reduced the doses of intrathecal morphine required for pain relief even several weeks after the cessation of the 24-day period of intrathecal S(+)-ketamine administration.

Analgesics↗

Dihydropyridine-induced Ca2+ release from ryanodine-sensitive Ca2+ pools in human skeletal muscle cells.

Dihydropyridines (DHPs) are widely used antihypertensive drugs and inhibit excitation-contraction (E-C) coupling in vascular smooth muscle and in myocardial cells by antagonizing L-type Ca2+ channels (DHP receptors). However, contradictory reports exist about the interaction of the DHP with the skeletal muscle isoform of the DHP receptor and E-C coupling in skeletal muscle cells. Using the intracellular fluorescent Ca2+ indicator fura-2, an increase in [Ca2+]i was observed after extracellular application of nifedipine to cultured human skeletal muscle cells. The rise in [Ca2+]i was dose dependent with a calculated EC50 of 614 +/- 96 nM nifedipine and a maximum increment in [Ca2+]i of 80 +/- 3.2 nM. Similar values were obtained with nitrendipine. This effect of DHPs was restricted to differentiated skeletal muscle cells and was not seen in non-differentiated cells or in PC12 cells. In spite of the observed increase in [Ca2+]i, whole-cell patch clamp experiments revealed that 10 microM nifedipine abolished inward Ba2+ currents through L-type Ca2+ channels completely. Similar to nifedipine, (+/-)Bay K 8644, an agonist of the L-type Ca2+ channel, also increased [Ca2+]i. This effect could not be enhanced by further addition of nifedipine, suggesting that both DHPs act via a common signalling pathway. Based on the specific mechanism of the skeletal muscle E-C coupling, we propose the stabilization of a conformational state of the DHP receptor by DHPs, which is sufficient to activate the ryanodine receptor.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Sister chromatid exchange in human lymphocytes exposed to isoflurane and nitrous oxide in vitro.

The question of whether or not inhalation anaesthetics are genotoxic remains controversial. Therefore, we have studied the in vitro genotoxic potential of isoflurane and nitrous oxide in human lymphocytes. Blood samples were obtained from eight healthy male, non-smoking volunteers, which were incubated and exposed to increasing concentrations of isoflurane (0.0, 0.3, 0.6 and 1.2 mmol litre-1) or 50% nitrous oxide in oxygen. Baseline sister chromatid exchange (SCE) rate per cell was mean 7.65 (SD 1.5) which increased to 9.15 (1.0), 9.55 (1.4) and 9.95 (1.8) SCE/cell during exposure to isoflurane 0.3, 0.6 and 1.2 mmol litre-1, respectively. During 50% nitrous oxide exposure, SCE rate was 9.26 (1.4). The difference between the control and exposed cells was statistically significant (P < or = 0.05). We conclude that exposure to nitrous oxide and subanaesthetic concentrations of isoflurane can produce genetic damage in peripheral lymphocytes in vitro.

Adult↗