Anna Spacek

Genetic damage in operating room personnel exposed to isoflurane and nitrous oxide

OBJECTIVES: To evaluate genetic damage as the frequency of sister chromatid exchanges and micronuclei in lymphocytes of peripheral blood of operating room personnel exposed to waste anaesthetic gases. METHODS: Occupational exposure was measured with a direct reading instrument. Venous blood samples were drawn from 10 non-smokers working in the operating room and 10 non-smoking controls (matched by age, sex, and smoking habits). Lymphocytes were cultured separately over 72 hours for each assay with standard protocols. At the end of the culture time, the cells were harvested, stained, and coded for blind scoring. The exchanges of DNA material were evaluated by counting the number of sister chromatid exchanges in 30 metaphases per probe or by counting the frequency of micronuclei in 2000 binucleated cells. Also, the mitotic and proliferative indices were measured. RESULTS: The operating room personnel at the hospital were exposed to an 8 hour time weighted average of 12.8 ppm nitrous oxide and 5.3 ppm isoflurane. The mean (SD) frequency of sister chromatid exchanges was significantly higher (10.2 (1.9) v 7.4 (2.4)) in exposed workers than controls (p = 0.036) the proportion of micronuclei (micronuclei/500 binucleated cells) was also higher (8.7 (2.9) v 6.8 (2.5)), but was not significant (p = 0.10). CONCLUSION: Exposure even to trace concentrations of waste anaesthetic gases may cause dose-dependent genetic damage. Concerning the micronuclei test, no clastogenic potential could be detected after average chronic exposure to waste anaesthetic gas. However, an increased frequency of sister chromatid exchanges in human lymphocytes could be detected. Although the measured differences were low, they were comparable with smoking 11-20 cigarettes a day. Due to these findings, the increased proportion of micronuclei and rates of sister chromatid exchanges may be relevant long term and need further investigation.

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 &mgr;g · kg−1 · min−1 up to 0.17 &mgr;g · kg−1 · min−1and 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 (ED50) were determined. Remifentanil led to a clear dose-dependent increase of the heat pain threshold differing significantly from placebo (P < 0.0007). The ED50 of remifentanil equals 0.05 &mgr;g · kg−1 · min−1 (first quartile 0.025 &mgr;g · kg−1 · min−1 and third quartile 0.06 &mgr;g · 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 &mgr;g · kg−1 · min−1 is an effective and safe increment in healthy volunteers. Implications This study investigated remifentanil as a single infused drug to determine its analgetic property. A dose-dependent effect was found in a human heat pain threshold assessment.

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.

Rocuronium-induced Neuromuscular Block Is Affected by Chronic Carbamazepine Therapy

BACKGROUND Patients on chronic anticonvulsant drugs are relatively resistant to certain nondepolarizing neuromuscular blockers such as pancuronium, vecuronium, pipecuronium, doxacurium, or metocurine, but not resistant to mivacurium and atracurium. This study investigated the influence of chronic carbamazepine therapy on the neuromuscular block induced by the new muscle relaxant rocuronium. METHODS Twenty-two otherwise healthy individuals scheduled for neurosurgical operations were studied: 11 of them were on chronic treatment with carbamazepine; the others served as control subjects. The median duration of carbamazepine therapy was 9 weeks (range, 4-312 weeks). After premedication with oral diazepam, anesthesia was induced with fentanyl and thiopental and maintained with nitrous oxide/oxygen and 0.5% inspired isoflurane. Rocuronium, 0.6 mg/kg (2 x ED95), was given for intubation. The ulnar nerve was stimulated, and the evoked electromyogram recorded using a Datex NMT monitor. RESULTS Based on the response to the first of four stimuli, neither the lag time nor the onset-time differed between the two groups. However, the intervals of recovery to 10%, 25%, 50%, and 75% of the baseline response and the recovery index (RI, 25%-75%) were significantly shorter in patients on chronic carbamazepine therapy. CONCLUSIONS The authors conclude that the duration of the rocuronium-induced neuromuscular block is significantly shortened by preceding chronic carbamazepine therapy.

Augmentation of the rocuronium-induced neuromuscular block by the acutely administered phenytoin.

BACKGROUND The effects of an acute administration of phenytoin on the magnitude of the rocuronium-induced neuromuscular block were evaluated. METHODS Twenty patients (classified as American Society of Anesthesiologists physical status I or II) scheduled for craniotomy were studied: 15 received phenytoin during operation (10 mg/kg), and the others served as controls. Anesthesia was induced with thiopental and fentanyl and maintained with nitrous oxide (65%) in oxygen and end-tidal isoflurane (1%). The ulnar nerve was stimulated supramaximally and the evoked electromyography was recorded using a neuromuscular transmission monitor. Continuous infusion of rocuronium maintained the neuromuscular block with first twitch (T1) between 10 and 15% for 45 min before the start of an infusion of either phenytoin or NaCl 0.9%. Twitch recordings continued for 60 min thereafter. Arterial blood samples were collected at the predefined time points (four measurements before and four after the start of the infusion) to determine the concentrations of phenytoin and rocuronium and the percentage of rocuronium bound to plasma proteins. RESULTS The first twitch produced by an infusion of rocuronium remained constant during the 15 min before and the 60 min after the start of the saline infusion. After the phenytoin infusion, the twitch decreased progressively, but the plasma concentrations and the protein-bound fraction of rocuronium did not change. CONCLUSION Phenytoin acutely augments the neuromuscular block produced by rocuronium without altering its plasma concentration or its binding to plasma proteins.

Gabapentin in der Therapie chronischer therapieresistenter Schmerzen

ZusammenfassungFragestellung. Untersuchung der Wirksamkeit und Verträglichkeit von Gabapentin bei der Behandlung von Patienten mit therapieresistenten Schmerzen. Methodik. Retrospektive Datenerhebung von Patienten mit chronischen therapieresistenten Schmerzen nach medikamentöser Vorbehandlung, die mit Gabapentin behandelt wurden. Ein Therapieerfolg wurde definiert als 50% Schmerzreduktion oder eine Schmerzintensität VAS ≤3. Ergebnisse. Annähernd die Hälfte der 99 Patienten (n = 49) wies einen Therapieerfolg auf. Patienten mit neuropathischen Schmerzen sprachen besser an (60% Responserate) als Patienten mit Schmerzen des Bewegungsapparates (35%). Allodynie trat vor der Therapie in der Gruppe der Therapieresponder doppelt so häufig auf (35 vs. 18%). Schwere Nebenwirkungen traten nicht auf. Schlussfolgerung. Gabapentin erwies sich als wirksames und verträgliches Medikament zur Behandlung neuropathischer Schmerzen.AbstractIntroduction. 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.

Ganglionic local opioid analgesia in refractory trigeminal neuralgia: Just a placebo? A randomized, controlled, double-blind, cross-over study

Abstract Introduction: The application of opioid drugs close to sympathetic ganglia (ganglionic local opioid analgesia, GLOA) has been reported to provide good pain relief in certain chronic pain syndromes. In the present prospective, randomized, double-blind, placebo-controlled, crossover study, the analgesic efficacy of GLOA versus saline injections was compared in patients suffering from refractory trigeminal neuralgia. Methods: A total of 19 patients were treated once a day for two 5-day periods with a series of either GLOA or saline injections, respectively, using a cross-over design. All applications were exclusively performed at the ganglion cervicale superius (GCS) of the affected side. The verum-GLOA consisted of 0.045 mg buprenorphine in 1.5 ml 0.9% NaCl, the placebo-GLOA of 1.5 ml 0.9% NaCl only. Pain reduction was measured with a visual analogue scale (VAS) before and after each injection. Data were analysed using analysis of variance. Results: Surprisingly, an almost identical, significant pa...

Aktuelle Schmerztherapie onkologischer Patienten

ZusammenfassungGrundlagen: Wenngleich Schmerz eines der häufigsten Symptome bei Patienten mit fortgeschrittener Tumorekrankung ist, gibt es den „Krebsschmerz” als solchen nicht. Schmerzen bei Krebspatienten können verschiedene Ursachen und pathogenetische Mechanismen zugrunde liegen und sowohl akuter als auch chronischer Natur sein.Methodik: In einer Übersicht werden die aktuellen Schmerztherapiekonzepte bei onkologischen Patienten zusammengestellt.Ergebnisse: Vor dem Beginn jeder Schmerzbehandlung muß eine genaue Schmerzanalyse erfolgen und eine Schmerzdiagnose gestellt werden, bevor ein Behandlungskonzept entwikkelt werden kann. Wegen der besonderen Situation des Krebskranken sollte die Schmerztherapie nach Möglichkeit von psychosozialen Maßnahmen begleitet sein. Das multimodale und interdisziplinäre Therapiekonzept beinhaltet daher meist eine Kombination mehrerer Verfahren, sowohl palliative Maßnahmen am erkrankten Organ (Operation, Chemo-, Radio- und Hormontherapie) als auch die symptomatische Schmerzbekämpfung. Wichtig ist ein rechtzeitiger Behandlungsbeginn nach WHO-Stufenschema mit oraler Analgetikagabe. Gegebenenfalls können Opioide auch parenteral bzw. rückenmarksnah mittels Katheders (epidural, intrathekal oder intraventrikulär) appliziert werden. Wenn der Schmerz segmental begrenzt auftritt, sollten bereits frühzeitig entsprechende temporäre oder definitive (neurolytische) regionale Blockaden eingesetzt werden.Schlußfolgerungen: Nur noch in äußerst seltenen Fällen müssen dekomprimierende und destruierende neurochirurgische Eingriffe als letzter Ausweg zur Schmerztherapie durchgeführt werden. Nichtinvasive Verfahren wie TENS (transkutane elektrische Nervenstimulation), physikalische Therapie, Akupunktur und psychologische Verfahren können mit gutem Erfolg begleitend zur Symptomlinderung beitragen.SummaryBackground: Pain often occurs in cancer patients and its treatment has to be according to the general guidelines for pain relief. As so-called cancer pain maybe caused by various mechanisms and can have both acute and chronic components, a detailed pain assessment followed by an at least preliminary pain diagnosis is necessary prior to symptomatic treatment. Many options for the therapy of cancer pain exist, and in most cases a proper combination of invasive and non-invasive approaches has to be chosen.Methods: The current concepts of pain management in cancer patients are reviewed.Results: Pain relief in cancer patients is commonly achieved by a multimodal, multidisciplinary concept, which includes palliative therapy of the malign process (surgery, radiation, etc.) and palliative symptomatic pain management. If the pain is well localized and restricted to certain peripheral parts of the body, spinal, peripheral or symphatic nerve blocking (temporary using local anesthetics) or permanent (using neurodestructive methods) may results in very good therapeutic effects. Analgesic pharmacotherapy should be carried out orally according to WHO guidelines for the treatment of cancer pain (so-called WHO analgesic ladder). In case of side effects, opioids may be alternatively applied via epidural or spinal catheters.Conclusions: In any case additional options such as TENS, SCS, physiotherapy, acupuncture or psychological approaches may be beneficial. Only if all these options fail, also neurosurgical destructive procedures are to be considered a last resort.

Akupunktur bei sympathischer Reflexdystrophie

Der Begriff sympathische Reflexdystrophie (SRD) faßt zahlreiche Krankheitsbilder, wie posttraumatisches Ödem, Schulter-Arm-Syndrom, Algodystrophie, Morbus Sudeck und Kausalgie, zusammen. Nach einem schädigenden Ereignis, jedoch unabhängig von dessen Art und Lokalisation, entwickelt sich typischerweise im distalen Bereich (Hand/Fuß) einer betroffenen Extremität eine Trias von autonomen, motorischen und sensiblen Störungen.Ziel der Therapie einer SRD ist in 1. Linie die Beseitigung von Schmerz und Schwellung. Vor allem physikalische Therapie ist wesentlich bei der Behandlung. Außerdem sollte möglichst früh invasiv sympathikolytisch behandelt werden. Auch Akupunktur kann die sympathische Aktivität reduzieren und analgetisch wirken, somit also dem Behandlungskonzept der SRD zumindest prinzipiell entsprechen. Während sich Hinweise auf eine sympathikolytische Wirkung der Akupunktur an distalen Extremitäten finden lassen, ist ihr möglicher therapeutischer Nutzen bei der SRD bisher nicht eindeutig nachgewiesen, jedoch zumindest diskussionswürdig.The term ”reflex sympathetic dystrophy” (RSD) is used for various syndromes, e.g. posttraumatic edema, shoulder-hand syndrome, algodystrophy and causalgia. The clinical symptoms of RSD are characterized by a triad of autonomic, sensory and motor disturbances, which usually develop in the distal region of an affected extremity. The main symptoms are swelling, a side difference in skin temperature (autonomic symptoms), reduced active movements and muscular strength (motor symptoms) and spontaneous, deep, diffuse pain with an orthostatic component (sensory system). As soon as possible the treatment of RSD should include sympatholytic strategies and obligatory physical therapy. Acupuncture has also been reported to reduce sympathetic activity. The analgestic effect of acupuncture is well known, and therefore from an at least theoretical point of view, it should make sense to use acupuncture in the treatment of RSD. To date, however, no prospective, randomized, controlled, clinical long-term studies have been done. One short-term study showed promising results, but did not reach statistical significance. In that study acupuncture treatment seemed to alleviate the major symptoms of RSD. Since acupuncture rarely has side effects, its role as an additional option in the treatment of RSD should be further investigated.

Does Chronic Anticonvulsant Therapy with Carbamazepine Affect the Atracurium Induced Neuromuscular Blockade

Whereas the actions of vecuronium (1), pancuronium (2) and doxacurium (3) are influenced by chronic anticonvulsant treatment with carbamazepine, neuromuscular blockade (NB) by atracurium seems to be unaffected.(4). Because of the existing controversy (5) on the influence of chronic anticonvulsant therapy on atracurium-induced NB, the present study was designed to examine the influence of carbamazepine on NB in neurosurgical patients.