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BACKGROUND Spironolactone (SPL) is a reversible mineralocorticoid receptor (MR) and androgen receptor (AR) antagonist which attracts pharmacotherapeutic interest not only because of its beneficial effects in heart failure but also because of the pathogenetic roles of MR and AR activities in neuropsychiatric diseases. Recently, beneficial and rapid-onset effects of SPL have been documented in a case series of women with fibromyalgia syndrome (FMS). To reaffirm this observation, we performed a double-blind placebo-controlled randomized clinical trial (RCT). METHODS A total of 69 patients were screened, 56 patients were eligible and randomized to SPL or placebo (each n = 28). Forty-three patients completed the clinical trial to the last visit (n = 21 and n = 22). After a run-in phase of 50 and 100 mg/day, 200 mg/day SPL or placebo were applied between days 7 and 28. Primary outcome was the change in the FIQ-G score (Fibromyalgia Impact Questionnaire, German version). Secondary outcome parameters were the changes in pain (numeric rating scale, NRS), mood (ADS), quality of life (SF-36) and change in FIQ scores 14 days after the end of the medication. RESULTS SPL of 200 mg/day did not change significantly either the primary or the secondary end points. SPL evoked a transient rise in serum potassium and a transient fall in GFR maximal after 2 weeks, but without clinical relevance. CONCLUSIONS SPL at 200 mg/day does not improve symptoms in women with FMS, but was considered not to cause harm. SIGNIFICANCE The mineralocorticoid receptor and androgen receptor antagonist spironolactone is repeatedly tested for its therapeutic effectivity against neuropsychiatric disorders. The present RCT demonstrated that 200 mg spironolactone does not change the symptoms of the fibromyalgia syndrome (FMS) in adult women. Between 2 and 4 weeks, spironolactone evokes a transient decrease in GFR and increase in serum potassium. Spironolactone cannot be recommended for the treatment of FMS.

The efficiency and quality of postoperative pain management may be considered unsatisfactory in Europe, as well as in the United States. Notwithstanding our better understanding of the physiology of pain and the development of new analgesia procedures, the improvement in satisfaction of patients has not be enhanced to the same degree. Obstetrics and gynecology are no exception to this statement. In fact, obstetrics and gynecology are surgical departments in which patients experience the greatest severity of postoperative pain. Current concepts of postoperative pain management are largely based on the administration of systemic non-opioid and opioid analgesics, supplemented with regional analgesia procedures and/or peripheral nerve blockades and, in some cases, the administration of other pain-relieving pharmaceutical agents. Based on the existing body of evidence, it would be appropriate to develop procedure-related concepts of analgesia. The concepts are based on the special circumstances of the respective department, and the scheme of analgesia is aligned to the respective interventions. Generally, however, a surgeon’s individual experience in dealing with the procedures and substances could be more significant than the theoretical advantages demonstrated in preceding investigations.

Das perioperative Management, beginnend bei der praoperativen Nutzen/Risiko-Bewertung uber die intraoperative Betreuung bis hin zur postoperativen Behandlung lebt von der Zusammenarbeit der beteiligten Disziplinen. Als Grundlage fur eine erfolgreiche interdisziplinare Kooperation gilt ein gegenseitiges Grundverstandnis der verschiedenen Fachbereiche. Das breite operative Spektrum der Gynakologie zwischen kleinen transvaginalen Eingriffen uber die Chirurgie der weiblichen Brust und laparoskopische Operationen bis hin zur Multiviszeralchirurgie bei Ovarialkarzinom hat prozedurenspezifische Auswirkungen auf das anasthesiologische Management. Diese beeinflussen nicht nur die Anasthesiefuhrung, sondern auch die Patientenauswahl und -vorbereitung durch den Operateur.

Das Achondroplasie-Syndrom ist die haufigste Form des genetisch bedingen Minderwuchses. Aufgrund der anatomischen Verhaltnisse ist das peripartale Management von Muttern mit Achondroplasie-Syndrom eine besondere Herausforderung und erfordert eine gute Zusammenarbeit zwischen den beteiligten Disziplinen. Als Geburtsmodus der Wahl gilt die Sectio caesarea, die sowohl in Allgemeinasthesie als auch in ruckenmarknaher Regionalanasthesie durchgefuhrt werden kann. In diesem Patientengut bieten beide Verfahren spezifische Vor- und Nachteile, die eine optimale Vorbereitung erforderlich machen. Insbesondere in geburtshilflichen Notfallsituationen ist daher eine enge Absprache zwischen beteiligten Geburtshelfern und Anasthesisten notwendig, um eine optimale Versorgung der Patientinnen sicherzustellen.

Propofol is widely used in routine clinical practice for the induction and maintenance of anaesthesia. Although propofol is regarded as a well tolerated anaesthetic, its effect on intact or damaged endothelial cells has not yet been elucidated.The aim of this study was to investigate the effects of different concentrations of propofol on cell damage, metabolic activity, barrier function and wound healing capacity of human endothelial cells.An in vitro investigation.Research Laboratory of the Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Kiel, Germany.In vitro cultures of primary human umbilical vein endothelial cells (HUVECs).Intact HUVEC or wounded HUVEC monolayers were incubated with or without different concentrations of propofol (10, 30 and 100 μmol l).Cell damage, metabolic activity, monolayer permeability, wound healing capacity, protein phosphorylation.Propofol did not alter the morphology, induce cell damage or influence metabolic activity of intact HUVEC cells. Permeability of a HUVEC monolayer was increased by propofol 100 μmol l (P 0.05). Wound closure was inhibited by the addition of propofol 30 and 100 μmol l (P 0.05 and P 0.01). This effect was associated with increased phosphorylation of extracellular signal regulated kinases (Erk) 1/2 (30 and 100 μmol l; both P 0.05) and decreased phosphorylation of Rho kinase (Rock) (100 μmol l; P 0.05).Propofol does not damage intact endothelial cells, but increases permeability of an endothelial cell monolayer at high concentrations and inhibits wound closure in vitro. Further experimental and clinical in vivo research should be performed to clarify the influence of propofol on endothelial wound healing.

Using animal models, volatile anesthetics have been recognized for their neuroprotective effects. Nevertheless, there is still disagreement about the optimal duration and timing of conditioning with the volatile anesthetic sevoflurane in the human system. In the study presented, we employed a human neuronal cell culture model to investigate the effects of hypoxia and to evaluate potential cytoprotective properties of different sevoflurane conditioning strategies. Sevoflurane was applied to human IMR-32 cells in which hypoxic conditions were induced for 2h using our recently described two-enzyme model (Zitta et al., Eur. J. Pharmacol., 2010). Cellular effects of hypoxia and sevoflurane conditioning were evaluated by lactate dehydrogenase (LDH) measurements, brightfield microscopy, ELISAs, cytometric bead arrays, Westernblotting and RT-PCR. Hypoxia increased the release of LDH into the culture medium after 24h (normoxia: 0.15+/-0.02 a.u; hypoxia: 0.69+/-0.08 a.u, P0.001) and expression of hypoxia associated genes HIF-1alpha, VEGF, catalase. Cytoprotective effects were observed in cultures that received sevoflurane for 30 min before hypoxia (preconditioning: 0.41+/-0.07 a.u., P0.01) and for 30 min during the hypoxic period (intraconditioning: 0.20+/-0.01 a.u., P0.001). Application of sevoflurane after the hypoxic insult did not lead to cytoprotection (postconditioning: 0.73+/-0.12a.u., P0.05). Conditioning with sevoflurane for a total of 3h before, during and after hypoxia, however, resulted in an enhanced release of LDH (periconditioning: 0.97+/-0.10a.u., P0.01) and additional cell damage. Hypoxia and sevoflurane intraconditioning were associated with changes in erk1/2 phosphorylation (T202/Y204) and HIF-1alpha protein levels, whereas phosphorylation of akt (S473) was not significantly altered. Our results suggest short pre- and intraconditioning with sevoflurane as most potent strategies to reduce hypoxia induced neuronal cell damage.

Objectives α2-Adrenergic and μ-opioid receptors belong to the rhodopsin family of G-protein coupled receptors and mediate antinociceptive effects via similar signal transduction pathways. Previous studies have revealed direct functional interactions between both receptor systems including synergistic and additive effects. To evaluate underlying mechanisms, we have studied whether morphine and fentanyl interacted with α2-adrenoceptor-subtypes in mice lacking one individual α2-adrenoceptor-subtype (α2-adrenoceptor knockout). Methods Opioid interaction with α2-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of α2A-, α2B- or α2C-adrenoceptor deficient mice. Displacement of the radiolabelled α2-adrenoceptor agonist [125I]paraiodoclonidine from α2-adrenoceptors in different brain regions by increasing concentrations of morphine, fentanyl and naloxone was analysed. The binding affinity of both opioids to α2-adrenoceptor subtypes in different brain regions was quantified. Key findings Morphine but not fentanyl or naloxone provoked dose-dependent displacement of [125I]paraiodoclonidine from all α2-adrenoceptor subtypes in the brain regions analysed. Binding affinity was highest in cortex, medulla oblongata and pons of α2A-adrenoceptor knockout mice. Conclusions Our results indicated that morphine interacted with α2-adrenoceptors showing higher affinity for the α2B and α2C than for the α2A subtype. In contrast, fentanyl and naloxone did not show any relevant affinity to α2-adrenoceptors. This effect may have an impact on the pharmacological actions of morphine.

BACKGROUND Delta9-tetrahydrocannabinol (Delta9-THC) induces analgesic effects and alterations of alertness. It has been reported that propofol increases endocannabinoid levels in the brain, but the effects of Delta9-THC on propofol sedation remain unclear. Our aim was to characterize the interaction between Delta9-THC and propofol in terms of sedation and analgesia. METHODS Sedation was monitored by a rota-rod and analgesia by tail-flick latencies. Twenty mice received intraperitoneal injections of 50 mg/kg Delta9-THC with 50, 75 and 100 mg/kg propofol after baseline values were established for each drug. Control experiments were performed with Delta9-THC and thiopental or Intralipid. RESULTS Injection of 50 mg/kg propofol caused a rapid onset of sedation with a minimum of 24 s on the rota-rod. Fifty mg/kg Delta9-THC alone had no sedative effects. Administration of Delta9-THC significantly reduced the sedative effect of propofol to at least 60 s on the rota-rod (P < 0.001). After increasing the propofol dose to 100 mg/kg in the presence of Delta9-THC, sedation was re-established with 27 s on the rota-rod. Thiopental sedation was significantly reduced (P < 0.01) in the presence of Delta9-THC. CONCLUSION The results indicate a dose-dependent antagonistic interaction between Delta9-THC and propofol, and also between Delta9-THC and thiopental.

alpha(2)-adrenoceptor agonists like clonidine or dexmedetomidine increase the sedative and analgesic actions of opioids. Furthermore opioids like meperidine show potent anti-shivering effects like alpha(2)-adrenoceptor agonists. The underlying molecular mechanisms of these effects are still poorly defined. The authors therefore studied the ability of four different opioids (meperidine, remifentanil, sufentanil and tramadol) to interact with different alpha(2)-adrenoceptor subtypes in mice lacking individual alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptors (alpha(2)-adrenoceptor knock out (alpha(2)-AR KO) mice)). The interaction of opioids with alpha(2)-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]-paraiodoclonidine ([(125)I]-PIC) from alpha(2)-adrenoceptors in different brain regions by increasing opioid concentrations was measured, and binding affinity of the analysed opioids to alpha(2)-adrenoceptor subtypes in different brain regions was quantified. Meperidine, remifentanil and tramadol but not sufentanil provoked dose dependent displacement of specifically bound [(125)I]-PIC from all alpha(2)-adrenoceptor subtypes in cortex, cerebellum, medulla oblongata, thalamus, hippocampus and pons. Required concentrations of meperidine and remifentanil for [(125)I]-PIC displacement from alpha(2B)- and alpha(2C)-adrenoceptors were lower than from alpha(2A)-adrenoceptors, indicating higher binding affinity for alpha(2B)- and alpha(2C)-adrenoceptors. In contrast, [(125)I]-PIC displacement by tramadol indicated higher binding affinity to alpha(2A)-adrenoceptors than to alpha(2B)- and alpha(2C)-adrenoceptors. Our results indicate that meperidine, remifentanil and tramadol interact with alpha(2)-adrenoceptors in mouse brain showing different affinity for alpha(2A)-, alpha(2B)- and alpha(2C)-adrenoceptors. In contrast, the micro-agonist sufentanil did not show any alpha(2)-adrenoceptor interaction. These effects may have an impact on the pharmacologic actions of these opioids.

To investigate if changes in low-to-high frequency ratio (LF/HF), low frequency (LF) and high frequency (HF) heart rate variability reflect autonomic regulation during spinal anaesthesia (SA) in pregnant women scheduled for elective Caesarean section.Prospective clinical trial. Systolic blood pressure (SBP) and heart rate variability were analysed at baseline, 5 min after SA and 15 min after SA. Patients were assigned by baseline LF/HF. Group LF/HF2.5 (n= 52) was compared to group LF/HF2.5 (n= 48). Non-parametric tests for statistical analysis.Group LF/HF2.5 showed a significant decrease in LF/HF and LF as well as an increase in HF during SA (median, range): baseline LF/HF [4.0 (3.2/4.8)] decreased to 2.3 (1.3/3.4) at event 15 min after SA (P0.001). Baseline LF = 59(43/71)% decreased to 40 (27/55)% at event 15 min after SA (P0.05). Baseline HF = 15(13/22)% increased to 26(15/41)% at event 15 min after SA (P0.05). In contrast, group LF/HF2.5 demonstrated only moderate changes in LF/HF, LF and HF during SA. SBP decreased significantly in group LF/HF2.5 (median and range) lowest SBP group LF/HF2.5: 80 (50/127 mmHg vs. group LF/HF2.5: 109 (104/142) mmHg, P0.001. Decrease of SBP before and after SA was correlated with a decrease in LF/HF, LF, and HF, respectively: LF/HF - SBP: r= 0.30, r(2)= 0.09, P0.001; LF - SBP: r= 0.25, r(2)= 0.06, P0.05, HF, NS.Changes in heart rate variability parameters in the course of SA may reflect a decrease in sympathetic activity and relative increase in parasympathetic activity as a result of the block. In the course of SA, the more pronounced the changes in heart rate variability were the more distinct the hypotension.

Background Hypotension due to vasodilation during subarachnoid block (SAB) for elective cesarean delivery may be harmful. Heart rate variability (HRV), reflecting autonomic control, may identify patients at risk of hypotension. Methods Retrospectively, HRV was analyzed in 41 patients who were classified into one of three groups depending on the decrease in systolic blood pressure (SBP): mild (SBP > 100 mmHg), moderate (100 > SBP > 80 mmHg), or severe (SBP < 80 mmHg). Prospectively, HRV and hemodynamic data of 19 patients were studied. Relative low frequency (LF), relative high frequency (HF), and LF/HF ratio were analyzed. Results Retrospective analysis of HRV showed a significantly higher sympathetic and lower parasympathetic drive in the groups with moderate and severe compared with mild hypotension before SAB (median, 25th/75th percentiles): LF/HF: mild: 1.2 (0.9/1.8), moderate: 2.8 (1.8/4.6), P < 0.05 versus mild; severe: 2.7 (2.0/3.5), P < 0.05 versus mild. Results were confirmed by findings of LF and HF. Prospectively, patients were grouped according to LF/HF before SAB: low-LF/HF: 1.5 (1.1/2.0) versus high-LF/HF: 4.0 (2.8/4.7), P < 0.05; low-LF: 58 +/- 9% versus high-LF: 75 +/- 10%, P < 0.05; low-HF: 41 +/- 10% versus high-HF: 25 +/- 10%, P < 0.05. High-risk patients had a significantly lower SBP after SAB (76 +/- 21 vs. 111 +/- 12 mmHg; P < 0.05). Conclusions Retrospectively analyzed HRV of patients scheduled to undergo elective cesarean delivery during SAB showed significant differences depending on the severity of hypotension after SAB. Preliminary findings were prospectively confirmed. High LF/HF before SAB predicted severe hypotension. Preoperative HRV analysis may detect patients at risk of hypotension after SAB.

Sepsis or systemic inflammatory response syndrome (SIRS) is often associated with encephalopathy (70%), which has been described as an early symptom resulting in several diseases. The present study investigated somatosensory evoked potentials (SEP) as an indicator or even a predictor of cerebral dysfunction evaluated in an experimental model of SIRS in pigs. Eight Gottinger minipigs were included in the study. SIRS was mediated by induction of pancreatitis due to injection (ductus pancreaticus) of 500 mg/kg sodium taurocholate and 2.5 IU/kg enterokinase. Monitored parameters were: arterial blood—central venous—pulmonary arterial pressure, and cardiac output, systemic vascular resistance, and body temperature. SEP were recorded from centroparietal vs. frontal areas after electrical stimulation of the right forepaw. At least 33% loss of vascular resistance from baseline (SIRS criteria) occurred in all animals within 4–18 h. Baseline recordings in all anesthetized animals indicated primary cortical responses to electrical stimuli identified by peak latencies between 15–20 ms (SEPP15–20). Attenuations in the amplitudes with significant median decreases of 46% were observed at least 4 h before the defined hemodynamic SIRS criteria. The present data show a trend for the attenuation in SEP amplitudes as an indicator of systemic inflammatory response. SEP monitoring may be a sensitive marker of developing early changes in cerebral function due to SIRS-related encephalopathy.

Der Einsatz von Weidenrinde, der bereits im Corpus Hippocraticum Erwahnung findet, wurde in der Neuzeit erstmals von Reverend Stone aus Oxfordshire vor mehr als 250 Jahren dokumentiert und stellt den Beginn der Verwendung von Nicht-Opioid-Analgetika dar. Im folgenden Jahrhundert wurde das Salicin als wirksames Agens der Weidenrinde identifiziert und durch die Synthese von Salicylsaure auch ein gezielter klinischer Einsatz moglich. Ein Meilenstein war die Synthese von Acetylsalicylsaure, die weitgehend unbeachtet erstmals wohl schon 1853 durch Gerhardt erfolgte, 1896 allerdings dem Bayer-Chemiker Felix Hoffman zugeschrieben wurde. Kurz danach wurde Acetylsalicylsaure von Heinrich Dresser auch als antipyretisches Analgetikum unter dem Handelsnamen Aspirin in die Klinik eingefuhrt. Danach verstrich nahezu ein 3/4 Jahrhundert, bis der Wirkungsmechanismus von Acetylsalicylsaure und seiner zahlreichen Nachfolgeprodukte - die Hemmung der Prostaglandinsynthese - in einer Bahn brechenden Arbeit von Sir John Vane aus dem Jahr 1971 identifiziert wurde.

alpha(2)-Adrenergic and mu-opioid receptors belong to the rhodopsin family of G-protein coupled receptors and mediate antinociceptive effects via similar signal transduction pathways. Previous studies have revealed direct functional interactions between both receptor systems including synergistic and additive effects. To evaluate underlying mechanisms, we have studied whether morphine and fentanyl interacted with alpha(2)-adrenoceptor-subtypes in mice lacking one individual alpha(2)-adrenoceptor-subtype (alpha(2)-adrenoceptor knockout).Opioid interaction with alpha(2)-adrenoceptors was investigated by quantitative receptor autoradiography in brain slices of alpha(2A)-, alpha(2B)- or alpha(2C)-adrenoceptor deficient mice. Displacement of the radiolabelled alpha(2)-adrenoceptor agonist [(125)I]paraiodoclonidine from alpha(2)-adrenoceptors in different brain regions by increasing concentrations of morphine, fentanyl and naloxone was analysed. The binding affinity of both opioids to alpha(2)-adrenoceptor subtypes in different brain regions was quantified.Morphine but not fentanyl or naloxone provoked dose-dependent displacement of [(125)I]paraiodoclonidine from all alpha(2)-adrenoceptor subtypes in the brain regions analysed. Binding affinity was highest in cortex, medulla oblongata and pons of alpha(2A)-adrenoceptor knockout mice.Our results indicated that morphine interacted with alpha(2)-adrenoceptors showing higher affinity for the alpha(2B) and alpha(2C) than for the alpha(2A) subtype. In contrast, fentanyl and naloxone did not show any relevant affinity to alpha(2)-adrenoceptors. This effect may have an impact on the pharmacological actions of morphine.

BACKGROUND AND OBJECTIVE Intravenously administered paracetamol is an effective analgesic in postoperative pain management. However, there is a lack of data on the effect of intravenous (i.v.) paracetamol on pain following soft tissue surgery. METHODS Eighty-seven patients undergoing elective breast surgery with total i.v. anaesthesia (propofol/remifentanil) were randomized to three groups. Group para received 1 g i.v. paracetamol 20 min before and 4, 10 and 16 h after the end of the operation. Group meta and plac received 1 g i.v. metamizol or placebo, respectively, scheduled at the same time points. All patients had access to i.v. morphine on demand to achieve adequate pain relief. RESULTS No significant difference in total morphine consumption between groups was detectable. The proportion of patients who did not receive any morphine in the postoperative period was significantly higher in group para (42%) than in group plac (4%). Ambulation was significantly (P < 0.05) earlier in group para (4.0 +/- 0.2 h) than in groups meta (4.6 +/- 0.2 h) and plac (5.5 +/- 1.0 h). No differences were observed between groups meta and plac. There were no differences between groups with regard to incidence of postoperative nausea and vomiting or changes in vigilance. CONCLUSION Neither i.v. paracetamol nor i.v. metamizol provided a significant reduction in total postoperative morphine consumption compared with placebo in the management of postoperative pain after elective breast surgery. Administration of paracetamol resulted in a significant reduction in the number of patients needing opioid analgesics to achieve adequate postoperative pain relief.

Introduction: We studied how effectively a mixed group of helpers could ventilate a manikin with a new rescue breathing device after a short period of instruction. The device consists of a mouthcap, a “glossopalatinal tube” (GPT) reaching between tongue and palate and a connector for a bag, ventilator or the rescuers mouth. Rather than reaching behind the tongue like an oropharyngeal airway (OP), it is able to scoop the tongue off the posterior pharyngeal wall when tilted by the rescuer. It was compared with a conventional face mask with an OP. Methods: The study made use of an anaesthesia simulator (MedSim Ltd., Israel) and a manikin. 46 subjects with different professional backgrounds (anaesthesia nurses, medical students, emergency medical technicians (EMTs), physicians training for anaesthesiology) underwent a standard introduction to the GPT and OP (lecture with demonstration on an intubation trainer, illustrated brochure). They ventilated the manikin for 5 min each using the bag plus GPT and the OP plus face mask, respectively, in random order after the simulator had been made apnoeic and the simulated arterial oxygen saturation (S aO 2 ) had dropped to 80%. The actions and the results (tidal volumes (V t ), S aO 2 ) were recorded on video. The subjects graded difficulty of operation and fatigue on a visual analogue scale (VAS). Results and conclusions: Mean V t with the OP plus mask amounted to 463 (230–688 ml), with GPT to 426 (243–610 ml) (median [10–90% percentiles]) ( P =0.047). No differences were observed with respect to the time a S aO 2 ≥90% was maintained (OP plus mask: 255 (139–266 s), GPT: 255 (90–269 s)) or the grades for fatigue (OP plus mask: 58% of VAS, GPT: 48% of VAS, median) and difficulty (OP plus mask: 16% of VAS, GPT: 21% of VAS). Performance and grades were scattered over a wide range. Success with the two devices was correlated, but the subjects judgement tended to diverge. The GPT is an easy to learn alternative to conventional devices and might be helpful in clinical emergencies, including situations of unexpectedly difficult ventilation.

To compare the quality of pain relief and incidence of side effects between 24-hr postoperative continuous epidural infusion (CEI) and subsequent patient-controlled epidural analgesia (PCEA) with different analgesics after major abdominal surgery.Twenty-eight women undergoing extended gynecological tumour surgery received postoperative CEI with 0.15 mL x kg(-1) x hr(-1) 0.2% ropivacaine (R: n = 14) or 0.125% bupivacaine plus 0.5 micro g x mL(-1) sufentanil (BS: n = 14) during 24 postoperative hours. Twenty-four hours later, postoperative pain management was switched to PCEA without background infusion and 5 mL single bolus application of R or BS every 20 min at most. Visual analogue scales (VAS; 1-100 mm) were assessed by patients at rest and on coughing after 24 hr of CEI and PCEA. Side effects, doses of local anesthetics and opioids were recorded and plasma concentrations of total and unbound ropivacaine and bupivacaine were measured.Patients required lower doses of each respective analgesic medication with PCEA (R: 108 +/- 30 mL; BS: 110 +/- 28 mL) than with CEI (R: 234 +/- 40; BS: 260 +/- 45; P0.01). Ropivacaine plasma concentrations were lower 24 hr after PCEA when compared with CEI (P0.01). No patient after PCEA but two after CEI (n = 4; NS) presented motor block. PCEA with R provided better postoperative pain relief than CEI (37 +/- 32 vs 59+/-27, P0.05). No difference in parenteral opioid rescue medication between CEI and PCEA was seen.PCEA in comparison to preceding CEI provides equivalent analgesia with lower local anesthetic doses and plasma levels, and without motor blocking side effects, irrespective of the applied drug regimen.

In light of evidence suggesting that hemofiltration favorably influences septic diseases by removing sepsis mediators, the impact of different modalities of continuous veno-venous hemofiltration (CVVH) on outcome and immunologic derangements in porcine pancreatogenic sepsis was evaluated.Randomized, controlled intervention trial.Forty-eight minipigs of either sex.Pancreatitis was induced by intraductal injection of sodium taurocholate (4%, 1 mL/kg body weight [BW]) and enterokinase (2 U/kg BW). Animals were allocated either to untreated controls-group 1-or to one of three treatment groups-group 2: low-volume CVVH (20 mL/kg BW), no change of hemofilters; group 3: low-volume CVVH, filters changed every 12 hrs; and group 4: high-volume CVVH (100 mL/kg BW), filters changed every 12 hrs. Survival represented the major parameter of the study. Serum cytokine levels, sepsis-related down-regulation of major histocompatibility complex II and CD14 expression on leukocytes, bacterial translocation, and endotoxemia were further parameters evaluated in the study.High-volume CVVH combined with periodic filter change was significantly superior compared with less intensive treatment modalities (low-volume CVVH, no filter change) in sepsis protection. Long-term survival (60 hrs) was found in 67% of group 4 and 33% of group 3 animals (p.05), whereas in controls and group 2 no animal survived. CVVH ameliorated the initial serum tumor necrosis factor-alpha response and prevented sepsis-induced in vitro endotoxin hyporesponsiveness. Down-regulation of major histocompatibility complex II and CD14 expression on monocytes was significantly improved by CVVH. Improved oxidative burst and phagocytosis capacity in polymorphonuclear leukocytes suggested that leukocyte function was stabilized by CVVH. Also, CVVH significantly reduced bacterial translocation and endotoxemia.Hemofiltration reversed sepsis-induced immunoparalysis in a porcine model of bile acid-induced pancreatitis. Implications for human pancreatitis must be validated in prospective, clinical protocols.

Background We investigated the influence of morphine and ketamine or clonidine in mice on the expression of genes that may mediate pronociceptive opioid effects. Material and Methods C57BL/6 mice received morphine injections thrice daily using increasing doses (5-20mg∙kg-1) for 3 days (sub-acute, n=6) or 14 days (chronic, n=6) and additionally either s-ketamine (5mg∙kg-1, n=6) or clonidine (0.1mg∙kg-1, n=6). Tail flick test and the assessment of the mechanical withdrawal threshold of the hindpaw was performed during and 4 days after cessation of opioid treatment. Upon completion of the behavioural testing the mRNA-concentration of the NMDA receptor (NMDAR1) and β-arrestin 2 (Arrb2) were measured by PCR. Results Chronic opioid treatment resulted in a delay of the tail flick latency with a rapid on- and offset. Simultaneously the mice developed a static mechanical hyperalgesia with a delayed onset that that outlasted the morphine treatment. Sub-acute morphine administration resulted in a decrease of NMDAR1 and Arrb2 whereas during longer opioid treatment the expression NMDAR1 and Arrb2 mRNA increased again to baseline values. Coadministration of s-ketamine or clonidine resulted in a reversal of the mechanical hyperalgesia and inhibited the normalization of NMDAR1 mRNA expression but had no effect on the expression of Arrb2 mRNA. Conclusion In the model of chronic morphine therapy the antinociceptive effects of morphine are represented by the thermal analgesia while the proniceptive effects are represented by the mechanical hyperalgesia. The results indicate that the regulation of the expression of NMDAR1 and Arrb2 may be associated to the development of OIH in mice. Perspective The results indicate that co-administration of clonidine or ketamine may influence the underlying mechanisms of OIH.