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Biomedical subjects

S Grond

Publications and source records attributed to S Grond.

At least 37 records · Page 2Linked to original sources
PubMed2000

Clinical pharmacokinetics of transdermal opioids: focus on transdermal fentanyl.

Transdermal delivery allows continuous systemic application of opioids through the intact skin. This review analyses the pharmacokinetic properties of transdermal opioid administration in the context of clinical experience, with a focus on fentanyl. A transdermal therapeutic system (TTS) for fentanyl has been developed. The amount of fentanyl released is proportional to the surface area of the TTS, which is available in different sizes. After the first application of a TTS, a fentanyl depot concentrates in the upper skin layers and it takes several hours until clinical effects are observed. The time from application to minimal effective and maximum serum concentrations is 1.2 to 40 hours and 12 to 48 hours, respectively. Steady state is reached on the third day, and can be maintained as long as patches are renewed. Within each 72-hour period, serum concentrations decrease gradually over the second and third days. When a TTS is removed, fentanyl continues to be absorbed into the systemic circulation from the cutaneous depot. The terminal half-life for TTS fentanyl is approximately 13 to 25 hours. The interindividual variability of serum concentrations, partly caused by different clearance rates, is markedly larger than the intraindividual variability. The effectiveness of TTS fentanyl was first demonstrated in acute postoperative pain. However, the slow pharmacokinetics and large variability of TTS fentanyl, together with the relatively short duration of postoperative pain, precluded adequate dose finding and led to inadequate pain relief or, especially, a high incidence of respiratory depression; such use is now contraindicated. Conversely, in cancer pain, TTS fentanyl offers an interesting alternative to oral morphine, and its effectiveness and tolerability in this indication has been demonstrated by a number of trials. Its usefulness in chronic pain of nonmalignant origin remains to be confirmed in controlled trials. In general, TTS fentanyl produces the same adverse effects as other opioids, mainly sedation, nausea, vomiting and constipation. In comparison with oral morphine, TTS fentanyl causes fewer gastrointestinal adverse events. The risk of hypoventilation is comparatively low in cancer patients. Sufentanil and buprenorphine may also be suitable for transdermal delivery, but clinical results are not yet available. Transdermal morphine is only useful if applied to de-epithelialised skin. However, iontophoresis may allow transdermal administration of opioids, including morphine, with a rapid achievement of steady state concentrations and the ability to adjust delivery rates. This would be beneficial for acute and/or breakthrough pain, and initial clinical trials are in progress.

Administration, Cutaneous↗
PubMed2000

New 1-O-acyl alpha-L-rhamnopyranosides and rhamnosylated lactones from Streptomyces sp., inhibitors of 3 alpha-hydroxysteroid-dehydrogenase (3alpha-HSD).

Chemical screening with extracts of Streptomyces sp. (strain GT 61150) resulted in the detection, isolation, and structure elucidation of two new acyl alpha-L-rhamnopyranosides (1 and 2) and three new rhamnosyllactones A, B1 and B2 (3 approximately 5). Rhamnosyllactones B1 and B2 were obtained as a 5:1 mixture. The structures were confirmed by spectroscopic analysis, especially 2D-NMR techniques. The rhamnosyltransferase of our strain is able to connect the sugar moiety to heteroaromatic carboxylic acids and enols. The metabolites 1 and 4/5 as well as previously reported acylrhamnosides 6 approximately 11 inhibit the enzyme 3alpha-hydroxysteroid-dehydrogenase (3alpha-HSD).

Enzyme Inhibitors↗
PubMed1999

[Switching opioids to transdermal fentanyl in a clinical setting].

INTRODUCTION: The use of transdermal fentanyl is gaining in importance in the management of cancer pain. We describe the reasons for switching opioid medication to transdermal fentanyl in a pain management unit. METHODS: Case records of patients treated with transdermal fentanyl in our pain clinic were evaluated retrospectively. Conversion ratios were calculated from the opioid dosage before and after conversion. Pain intensities were assessed on a numeric rating scale (NRS 0: no pain, 10: worst pain imaginable). RESULTS: From October 1995 to December 1997 101 patients received transdermal fentanyl. Thirty-six patients had been treated with transdermal fentanyl before admission to our pain clinic, and relevant information was missing for one patient, so 64 patients were evaluated. Opioid therapy was switched to transdermal fentanyl during in-patient treatment for 53 patients and during out-patient treatment for 11 patients. Before conversion patients were treated with slow-release morphine (48%), immediate-release morphine (17%), buprenorphine (11%), tramadol (11%), levomethadone (5%), tilidine/naloxone (5%) and piritramid (3%). Reasons for opioid rotation were inadequate pain relief ( 33%), the patients' wish to reduce oral medication (20%), gastrointestinal side effects such as nausea (31%), vomiting (13%) and constipation (19%), dysphagia (27%) or others. Reduction of side effects was reported by 10 of 19 patients. In 12 of 21 patients, in whom the medication was switched because of inadequate pain relief, a reduction in pain intensity was reported. DISCUSSION: Conversion to transdermal therapy may readjust the balance between opioid analgesia and side effects. The opioid switch resulted in more pain relief or fewer side effects in half of the patients. A proposed equianalgesic conversion ratio between 70:1 and 100:1 from oral slow-release morphine to transdermal fentanyl can be confirmed by our data. Conversion rates from other opioids to transdermal fentanyl are suggested.

English Abstract↗
PubMed1999

Temporal presentation of chronic cancer pain: transitory pains on admission to a multidisciplinary pain clinic.

Transitory flares of pain are well-recognized events in both untreated and treated patients suffering from chronic cancer pain. For the purpose of this survey, we refer to transitory pain (TP) as any event subjectively characterized by transience and pain intensity over a baseline pain. In Part I, TP was reported by 243 (39%) of 613 consecutive cancer pain patients. Gender, age, tumor site, stage, and therapy were not related to the presence of TP. Neuropathic baseline pain was associated with a higher prevalence of TP (P < 0.0001). TP was somatic in 39%, visceral in 22%, and neuropathic in 36% of patients. TP intensity was severe or worse in 92% of patients. Neuropathic TP was briefer and occurred more frequently than nociceptive TP. In Part II, further features of TP were surveyed in 55 patients. Patients reported spontaneous occurrence of TP (40%), a relationship to movement (36%), to the analgesic regimen (35%), to coughing (11%), and to various other factors (18%). Only half of the movement-related TP were predictable. Rescue medication was at least partially effective in 75% of patients. Change in position, rest, diversion, and physiotherapy were commonly employed to alleviate TP. This survey outlined a framework to characterize TP that may prove useful to clarify the definition, pathophysiology, and prevalence of these pains.

Adolescent↗
PubMed1999

High-dose tramadol in comparison to low-dose morphine for cancer pain relief.

Cancer pain treatment following the World Health Organization guidelines is effective and feasible. However, the evidence supporting the use of opioids for mild to moderate pain on the second step of the analgesic ladder is widely discussed. The present evaluation compares the efficacy and safety of high doses of oral tramadol (> or = 300 mg/d) with low doses of oral morphine (< or = 60 mg/d). Patients were included in this nonblinded and nonrandomized study if the combination of a nonopioid analgesic and up to 250 mg/d of oral tramadol was inadequate. 810 patients received oral tramadol for a total of 23,497 days, and 848 patients received oral morphine for a total of 24,695 days. The average dose of tramadol was 428 +/- 101 mg/d (range 300-600 mg/d); the average dose of morphine was 42 +/- 13 mg/d (range 10-60 mg/d). Additional nonopioid analgesics were given on more than 95% of days. Antiemetics, laxatives, neuroleptics, and steroids were prescribed significantly more frequently in the morphine group; the use of other adjuvants was similar in both groups. The mean pain intensity on a 0-100 numerical rating scale (NRS) was 27 +/- 21 (95% CI 26-29) in the tramadol and 26 +/- 20 (95% CI 24-27) in the morphine group (NS). The analgesic efficacy was good in 74% and 78%, satisfactory in 10% and 7%, and inadequate in 16% and 15% of patients receiving tramadol and morphine, respectively (NS). Constipation, neuropsychological symptoms, and pruritus were observed significantly more frequently with low-dose morphine; other symptoms had similar frequencies in both groups. These data suggest that tramadol can be used for the treatment of cancer pain, when nonopioids alone are not effective. High doses of tramadol are effective and safe.

Aged↗
PubMed1999

Validation of the German version of the Brief Pain Inventory.

The Brief Pain Inventory is a comprehensive instrument for pain assessment and has been validated in several languages. A validated German version was not available until now. From March to May 1995 all outpatients of the pain clinic of the Department of Anesthesiology completed a questionnaire with the German versions of the Brief Pain Inventory (BPI) and the SF-36 quality-of-life questionnaire. The BPI was repeated after the consultation. The physician assessed the performance status score of the Eastern Cooperative Oncology Group (ECOG). The questionnaire was completed by 151 patients. Forty-two patients were excluded from evaluation for methodological reasons, so 109 patients were evaluated. As in the original version of the BPI, factor analysis showed a common factor for pain intensity and a second factor for pain-related interference with function. The comparative fit index of 0.86 confirmed this model. Responses before and after consultation correlated closely for the sum scores of the pain intensity items (Perarson correlation r = 0.976) as well as for the interference with function items (r = 0.974). Pain intensity in the BPI correlated with bodily pain in the SF-36 (r = 0.585). Sum scores of the pain interference items were higher in patients with deteriorated ECOG performance status, whereas sum scores of the intensity items were not changed. Validity and reliability of the German BPI were comparable to the original version. The BPI may be advantageous for palliative care patients, as it places only a small burden on the patient and offers easy criteria for evaluation. However, further research is needed to differentiate the impact of pain-related and disease-related interference with function on the BPI, and to find an algorithm for the evaluation of the BPI when values are missing.

Adult↗
PubMed1999

Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery.

The authors' recent experimental work has demonstrated that myocardial protection using continuous coronary perfusion with warm beta-blocker-enriched blood avoids myocardial ischaemia and minimizes myocardial oedema formation, thus completely preserving left ventricle function. The purpose of this clinical study was to compare this alternative technique in terms of structural and functional myocardial protection with the routinely used crystalloid Bretschneider cardioplegia. Sixty coronary artery surgery patients were randomized to receive either crystalloid cardioplegia or continuous coronary perfusion with warm blood enriched with the ultra-short acting beta-blocker esmolol. Cardiac function was evaluated using transoesophageal echocardiography (fractional area of contraction) and cardiac metabolism using arterial-coronary sinus lactate concentration difference (a - csD(LAC)). From left ventricular biopsies, the authors determined myocardial oedema, heat-shock-protein-70, intercellular-adhesion-molecule and actin pattern. Patients with crystalloid cardioplegia received 3.6 +/- 0.8 grafts during 64 +/- 20 min cross-clamp time (beta-blocker: 3.5 +/- 0.9 grafts during 68 +/- 22 min; NS). Following cross-clamp removal crystalloid cardioplegia hearts released significant lactate amounts (a- csD(LAC)) - 1.0 +/- 0.6 versus - 0.1 +/- 0.2 mmol/litre in beta-blocker hearts; P < 0.05). In crystalloid cardioplegia hearts, myocardial water content increased from 82.1 +/- 2.1% pre-cardiopulmonary bypass to 83.2 +/- 1.7% at the end of cardiopulmonary bypass (P < 0.05); in beta-blocker hearts myocardial water content remained unchanged (pre-cardiopulmonary bypass: 82.3 +/- 1.9%; end of cardiopulmonary bypass: 82.4 +/- 1.7%; NS). At the end of cardiopulmonary bypass, left ventricular biopsies of beta-blocker hearts showed less structural damage as determined by heat shock protein-70, intercellular adhesion molecule-I and deranged actin cross-striation pattern as compared with crystalloid cardioplegia hearts (P < 0.05). The post-cardiopulmonary bypass fractional area of contraction was similar in both groups (beta-blocker: 65 +/- 14%; crystalloid cardioplegia: 62 +/- 16%); however, beta-blocker patients required less inotropic stimulation (dopamine: beta-blocker: 2.9 +/- 2.5 versus crystalloid cardioplegia: 5.0 +/- 2.3 microg/kg per min; P < 0.05). The data suggest that continuous coronary perfusion with warm esmolol-enriched blood results in better myocardial protection compared with crystalloid cardioplegia. It is concluded that the concept of beta-blocker-induced cardiac surgical conditions may be a useful alternative for myocardial protection during coronary artery surgery.

Adrenergic beta-Antagonists↗
PubMed1999

Serum concentrations of tramadol enantiomers during patient-controlled analgesia.

AIMS: Tramadol, a centrally acting analgesic, is used as a racemate containing 50% of a (+)- and 50% of a (-)-enantiomer. This paper presents the pharmacokinetic results of postoperative patient-controlled analgesia using (+)-tramadol, (-)-tramadol or the racemate. METHODS: Ninety-eight patients recovering from major gynaecological surgery were treated in a randomised, double-blind study with (+)-tramadol, (-)-tramadol or the racemate. Following an i.v. bolus up to a maximum of 200 mg, patient-controlled analgesia with demand doses of 20 mg was made available for 24 h. Prior to each demand, the serum concentrations of the enantiomers of tramadol and its metabolite M1 were measured in 92 patients. RESULTS: The mean concentrations of tramadol during the postsurgery phase were 470+/-323 ng ml-1, 590+/-410 ng ml-1 and 771+/-451 ng ml-1 in the (+)-, racemate- and (-)-group, respectively ((+) vs (-), P<0.05); the mean concentrations of the metabolite M1 were 57+/-18 ng ml-1, 84+/-34 ng ml-1 and 96+/-41 ng ml-1 in the (+)-, racemate- and (-)-group, respectively ((+) vs (-) and (+) vs racemate, P<0.05). The mean concentrations of (+)-tramadol and (+)-M1 were lower in the racemate- than in the (+)-group (P<0.05), those of (-)-tramadol and (-)-M1 were lower in the racemate than in the (-)-group (P<0.05). In the racemate group, the mean serum concentrations of (+)-tramadol were higher than those of (-)-tramadol (P<0.05), whereas the mean serum concentrations of (-)-M1 were higher than those of (+)-M1 (P<0. 05). CONCLUSIONS: The therapeutic serum concentration of tramadol and M1 showed a great variability. The lowest mean concentrations were measured in the (+)-group and the highest in (-)-group. This is in agreement with the clinical finding that (+)-tramadol is a more potent analgesic than (-)-tramadol.

Adult↗
PubMed1999

Responders and non-responders to post-operative pain treatment: the loading dose predicts analgesic needs.

The study compares responders and non-responders to post-operative patient-controlled analgesia (PCA) and evaluates factors that might differ between these two groups in order to identify non-responders during the early post-operative period. A prospective, randomized, double-blinded study design was used. Patients recovering from abdominal surgery were assigned to one of three treatment groups for a study period of 48 h. After titration of an individual loading dose, patients could self-administer 1 mL bolus doses (2 mg of morphine, 20 mg of tramadol or placebo) using a PCA device. Patients responding or not responding to the treatment were identified. In non-responders the escape medication was morphine. There were 96 responders and 65 non-responders. All responders showed similar pain scores, irrespective of the drug they received. Drug consumption of placebo responders was twice as high as that of opioid responders. Pain scores and analgesic consumption of non-responders were significantly higher compared with responders, although those patients received morphine. The loading dose correlated with subsequent analgesic consumption. Altogether, 89.2% of the non-responders were identified after the loading dose. Size of loading dose and pain scores during the first 30 min are useful for assessing the overall response to post-operative pain management. These factors may be valuable for predicting individual pain management.

Abdomen↗
PubMed1999

Surveys on the use of regional anaesthesia in obstetrics.

Regional anaesthetic techniques in obstetrics have gained more and more importance during the last few years. Several surveys published recently show a remarkable increase in caesarean sections performed under regional anaesthesia, in many countries. Furthermore, epidural analgesia has proved to be one of the most effective methods of pain relief during vaginal delivery. Especially in patients at risk of an abdominal delivery, an epidural catheter already in place during labour can be used for consecutive caesarean section without delay and is used as a strong argument in favour of epidural anaesthesia. This article gives an overview of recent surveys of regional anaesthesia in obstetrics.

Journal Article↗
PubMed1998

[Ketorolac and butylscopolamine in combination with alfentanil for renal lithotripsy].

BACKGROUND: Patient-controlled analgesia (PCA) using intravenous alfentanil provides adequate pain relief during extracorporal shock wave lithotripsy (ESWL) of renal stones. Occasional disadvantages of opioid analgesia include nausea, sedation and respiratory depression. This double-blind, placebo-controlled study examined whether the alfentanil requirements and thereby the frequency of side effects could be reduced by preemptive analgesia with the non-opioid analgesic ketorolac or the spasmolytic butylscopolamine. METHODS: 90 patients scheduled for ESWL of renal stones received 1 hour prior to ESWL ketorolac 30 mg, butylscopolamine 20 mg or placebo intramusculary. 10 mg of metoclopramide and 6.6 microg/kg of alfentanil were given intravenously at the beginning of ESWL (Philips/Dornier MFL 5000). Intravenous PCA was started (demand dose: 0.25 mg of alfentanil, lockout time: 1 minute). Pain intensity (NRS 0-100), sedation score (VRS 0-4), respiratory rate (min(-1)) and partial oxygen saturation (SO(2)) were measured every 5 minutes. Statistical analysis included ANOVA and Chi-square-test (p<0,05). RESULTS: Demographic and ESWL data were comparable between the study groups. However, patients of the ketorolac group were statistically significantly younger than those in the other groups. Alfentanil doses, pain scores and frequency of respiratory depression, sedation and nausea were lower subsequent to ketorolac than subsequent to butylscopolamine or placebo (not statistically significant). Signs of respiratory depression were only seen during ESWL. CONCLUSIONS: The present study confirms that PCA using alfentanil is effective during ESWL of renal stones. However, because of the possibility of respiratory depression, adequate monitoring is mandatory. Preemptive analgesia with 30 mg of ketorolac or 20 mg of butylscopolamine cannot reduce alfentanil requirements or improve efficacy and safety.

Clinical Trial↗
PubMed1998

[Weak opioids. Meta-analysis for the therapy of chronic pain].

Weak opioids have a maximal dose (ceiling effect), and their distribution and prescription is not controlled by German narcotic laws. In a literature search (Medline 1963-1995) and our own literature database on pain treatment, 58 publications were identified. These reported about 130 comparisons of weak opioids with different analgesics. The statistical parameters of a meta-analysis were not calculated, due to great differences of the study design and the examined drugs. The results of this literature analysis demonstrate the analgesic efficacy of weak opioids in chronic pain. Non-opioid analgesics and strong opioids, however, have greater potency. These results are based mainly on single-dose studies; controlled long-term studies are required. Especially the risk of serious complications involving the gastrointestinal tract, kidney and blood cells during long-term treatment with non-opioid analgesics or weak opioids needs to be evaluated. In addition, the combination of non-opioid analgesics and weak opioids versus the combination of nonopioid analgesics and placebo or low-dose strong opioids has to be investigated. The results of this literature analysis support the use of weak opioids in the symptomatic treatment of chronic pain, though the evidence of the available literature is limited. It can be recommended to prescribe weak opioids according to the WHO ladder in combination with non-opioid analgesics. If this combination provides no adequate analgesic efficacy, however, the use of strong opioids must not be delayed.

English Abstract↗
PubMed1998

[Anesthesia for cesarean section in Germany. A survey].

AIM OF STUDY: Goal of this survey is to give an overview of anaesthesia for caesarean section in Germany. METHOD: In 1994 and 1995, we sent a questionnaire to the chief-anaesthetists of all German hospitals with departments of gynaecology/obstetrics to find out the routine anaesthetic procedures for caesarean section. RESULTS: We obtained data from 409 hospitals (response rate 46.4%) with 321,816 births--50,123 of which were sections (mean caesarean section rate 16.6%). The mean general anaesthesia rate for elective caesarean sections was 66.5%, for non-elective sections 90.8%. The mean epidural anaesthesia rate for caesarean section was 22.6% and the mean spinal anaesthesia rate was 9.8%. For general anaesthesia most hospitals used antacids and/or histamine2-receptor antagonists (64.6% of responding hospitals). Anaesthesia was induced with intravenous barbiturates (82%), succinylcholine for intubation (98.2%) and no opioids before clamping of the cord (94.8%). For regional anaesthesia bupivacaine was the most common local anaesthetic (spinal 84.0%, epidural 96.8%). Opioids were added to local anaesthetics for epidural anaesthesia at 21.4% of the hospitals. CONCLUSIONS: General anaesthesia is the commonest practice for caesarean sections at German hospitals. Nowadays regional anaesthesia gains more importance compared to previous German surveys and in agreement with foreign data.

Anesthesia, Epidural↗
PubMed1998

Weak opioids--an educational substitute for morphine?

The World Health Organization guidelines suggest the use of weak opioids on the second step of the analgesic ladder for cancer pain relief. Weak opioids are important substitutes for low doses of morphine, although their analgesic efficacy is lower than that of non-opioid or strong opioid analgesics. The use of weak opioids has great educational impact and has helped spread the use of the guidelines. Furthermore, weak opioids are more freely available and are expected to have a better side-effect profile. Controlled long-term studies are required for confirmation.

Journal Article↗
PubMed1998

A retrospective study of the effects of small-dose aprotinin on blood loss and transfusion needs during total hip arthroplasty.

Aprotinin is a proteinase inhibitor that reduces blood loss in total hip arthroplasty when administered in large doses. Little is known about the capability of smaller doses of aprotinin in reducing blood loss and transfusion needs in this surgical setting. We reviewed the medical records of 372 patients who had undergone unilateral primary total hip arthroplasty under general anaesthesia during a 6-year period (1989 to 1994) at our institution. Successively, 193 patients had and 179 patients had not received aprotinin in a dose of 20,000 kallikrein inhibitor units per kilogram body weight intravenously before surgery. Neither the volume of red blood cells lost nor that of red blood cells transfused during hospitalization differed significantly between the patients who had and those who had not received aprotinin (520 +/- 406 vs. 549 +/- 394 mL and 463 +/- 379 vs. 475 +/- 367 mL; P = 0.49 and P = 0.76 respectively). These results suggest that small-dose aprotinin was not effective in reducing blood loss and transfusion needs in patients undergoing unilateral primary total hip replacement.

Aged↗
PubMed1998

[Out-patient hospice services--their importance for palliative care in Germany].

Hospice services can be divided into three groups. Few institutions deliver the full scope of palliative home care, most of the others can provide considerably less. The third group of services are those that do not support patients but aim to establish a home care service or a hospice. In February, 1997 396 home care services were working in Germany. 48 of these services provided palliative home care, 69 services were hospice initiatives. The scope of services rendered is very broad and reaches from psychosocial support to complex medical tasks. In the last year, 13,700 patients have been supported at home by hospice services in Germany. Palliative care services usually have professional staff, but they would not be able to work without honorary help. Beside of support for patients and relatives tasks of the home care service are the coordination and exchange between in-patient units, general physicians and social care ward. By cooperation with all institutions for out-patient and home care as well as with general physicians, they contribute to avoid in-patient treatment for their patients. Another important function is to spread the hospice idea and work as multipliers for knowledges and attitudes in palliative care. The number of home care services available in Germany is not sufficient. Only 48 institutions can be ranked as palliative care services. The distribution of the hospice services in Germany is very irregular, and providers of home care services are even more scarce in the eastern part of Germany.

Germany↗