Postoperative pain management after ambulatory surgery. A survey of anaesthesiologists

Data on practice and quality of postoperative pain treatment by anaesthesiologists after ambulatory surgery are sparse. The current survey enrolled anaesthesiologists in private practice who were responsible for pain therapy after ambulatory surgery. The aim of this investigation was to evaluate the implementation of the German S3 guidelines for acute and postoperative pain therapy in the outpatient setting.

Schmerzmanagement bei Kindern in der Schweiz

Hintergrund Schmerzen bei stationär aufgenommenen Kindern werden häufig unzureichend behandelt. Bisher gab es keine Informationen zum Schmerzmanagement von Kinderkrankenhäusern in der Schweiz. Ziel der vorliegenden Studie war, den aktuellen Stand der Schmerzerfassung, -interpretation und -behandlung zu bestimmen. Studiendesign Ein Fragebogen wurde an alle pädiatrischen Krankenhäuser in der Schweiz gesendet. Ergebnisse Insgesamt antworteten 27 von 45 Einheiten (Antwortrate: 60%). Die meisten Abteilungen verwenden Schmerzerfassungstools (96%) und führten diesbezügliche Leitlinien ein (78%). Die Behandlung von Schmerzen erfolgt ebenfalls meist nach hausinterner Leitlinie (78%). Prozedurale und postoperative Schmerzen werden stets (100%) analgetisch behandelt. Bei Frühgeborenen und Kindern auf Intensivpflegestationen werden bei invasiven Eingriffen häufig Analgetika (> 87%) verwendet. Auf Intensivstationen liegen in 44% diesbezügliche Leitlinien vor. Resümee Der Nutzen eines effektiven Schmerzmanagements bei Kindern ist eindeutig belegt. Viele Ansätze zur Verbesserung werden in der Schweiz gut umgesetzt. Vor allem im internationalen Vergleich verbesserte sich das Schmerzmanagement. Es gibt aber noch Optimierungsmöglichkeiten. Beispielsweise besitzen weniger als die Hälfte aller schweizerischen Intensivstationen eine Leitlinie für die Behandlung von Schmerzen bei invasiven Eingriffen.

Evaluation of smell and taste in patients with Wegener's granulomatosis

Although a reduced olfactory/gustatory function affects patients in all parts of life, this problem has not received much attention in Wegener's granulomatosis (WG). The aim of this study was to assess the smell/taste function of WG patients. Demographic data of 16 WG patients (9 males, 7 females) were obtained. They all subjectively assessed their taste/smell function on visual analogue scale. Olfactory/gustatory functions of the patients were tested with 'Sniffin' Sticks and 'Taste' strips, respectively. The results were then compared with those from sex and age-matched control group (n = 16) and normative data. WG patients subjectively assessed their olfactory (p = 0.03) and gustatory (p = 0.02) function to be lower than control group. All the olfactory scores (odour identification, odour discrimination and threshold) in both genders were significantly below the scores in the control group. WG patients were hyposmic. For taste (total taste score, as well as scores for the qualities sweet, sour, salty and bitter), WG patients did not significantly differ from controls and were normogeusic. However, the gustatory scores showed the tendency of reduction as compared to the control group. In conclusion, WG patients truly suffer from olfactory/taste dysfunction, but this is worse with olfaction. It is, therefore, imperative that physicians should make their patients to be aware of these sensory dysfunctions and educate them on methods to cope with it for better quality of life.

Autofluorescence endoscopy in surveillance of Barrett's esophagus: a multicenter randomized trial on diagnostic efficacy

BACKGROUND AND STUDY AIMS: The reference surveillance method in patients with Barrett's esophagus is careful endoscopic observation, with targeted as well as random four-quadrant biopsies. Autofluorescence endoscopy (AFE) may make it easier to locate neoplasia. The aim of this study was to elucidate the diagnostic accuracy of surveillance with AFE-guided plus four-quadrant biopsies in comparison with the conventional approach. PATIENTS AND METHODS: A total of 187 of 200 consecutive Barrett's esophagus patients who were initially enrolled (73 % male, mean age 67 years, mean Barrett's segment length 4.6 cm), who underwent endoscopy for Barrett's esophagus in four study centers, were randomly assigned to undergo either AFE-targeted biopsy followed by four-quadrant biopsies or conventional endoscopic surveillance, also including four-quadrant biopsies (study phase 1). After exclusion of patients with early cancer or high-grade dysplasia, who underwent endoscopic or surgical treatment, as well as those who declined to participate in phase 2 of the study, 130 patients remained. These patients were examined again with the alternative method after a mean of 10 weeks, using the same methods described. The main study parameter was the detection of early cancer/adenocarcinoma or high-grade dysplasia (HGD), comparing both approaches in study phase 1; the secondary study aim in phase 2 was to assess the additional value of the AFE-guided approach after conventional surveillance, and vice versa. Test accuracy measures were derived from study phase 1. RESULTS: In study phase 1, the AFE and conventional approaches yielded adenocarcinoma/HGD rates of 12 % and 5.3 %, respectively, on a per-patient basis. With AFE, four previously unrecognized adenocarcinoma/HGD lesions were identified (4.3 % of the patients); with the conventional approach, one new lesion (1.1 %) was identified. Of the 19 adenocarcinoma/HGD lesions detected during AFE endoscopy in study phase 1, eight were visualized, while 11 were only detected using untargeted four-quadrant biopsies (sensitivity 42 %). Of the 766 biopsies classified at histology as being nonneoplastic, 58 appeared suspicious (specificity 92 %, positive predictive value 12 %, negative predictive value 98.5 %). In study phase 2, AFE detected two further lesions in addition to the initial alternative approach in 3.2 % of cases, in comparison with one lesion with conventional endoscopy (1.7 %). CONCLUSIONS: In this referral Barrett's esophagus population with a higher prevalence of neoplastic lesions, the AFE-guided approach improved the diagnostic yield for neoplasia in comparison with the conventional approach using four-quadrant biopsies. However, AFE alone was not suitable for replacing the standard four-quadrant biopsy protocol.

Neural correlates of antinociception in borderline personality disorder

CONTEXT: A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain. OBJECTIVE: To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD. DESIGN: Case-control study. SETTING: A university hospital. PARTICIPANTS: Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects. INTERVENTIONS: Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants. MAIN OUTCOME MEASURE: Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation. RESULTS: Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD. CONCLUSION: The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

Geriatric Pain Measure short form: development and initial evaluation

OBJECTIVES: To develop and evaluate a short form of the 24-item Geriatric Pain Measure (GPM) for use in community-dwelling older adults. DESIGN: Derivation and validation of a 12-item version of the GPM in a European and an independent U.S. sample of community-dwelling older adults. SETTING: Three community-dwelling sites in London, United Kingdom; Hamburg, Germany; Solothurn, Switzerland; and two ambulatory geriatrics clinics in Los Angeles, California. PARTICIPANTS: European sample: 1,059 community-dwelling older persons from three sites (London, UK; Hamburg, Germany; Solothurn, Switzerland); validation sample: 50 persons from Los Angeles, California, ambulatory geriatric clinics. MEASUREMENTS: Multidimensional questionnaire including self-reported demographic and clinical information. RESULTS: Based on item-to-total scale correlations in the European sample, 11 of 24 GPM items were selected for inclusion in the short form. One additional item (pain-related sleep problems) was included based on clinical relevance. In the validation sample, the Cronbach alpha of GPM-12 was 0.92 (individual subscale range 0.77-0.92), and the Pearson correlation coefficient (r) between GPM-12 and the original GPM was 0.98. The correlation between the GPM-12 and the McGill Pain Questionnaire was 0.63 (P<.001), similar to the correlation between the original GPM and the McGill Pain Questionnaire (Pearson r=0.63; P<.001). Exploratory factor analysis indicated that the GPM-12 covers three subfactors (pain intensity, pain with ambulation, disengagement because of pain). CONCLUSION: The GPM-12 demonstrated good validity and reliability in these European and U.S. populations of older adults. Despite its brevity, the GPM-12 captures the multidimensional nature of pain in three subscales. The self-administered GPM-12 may be useful in the clinical assessment process and management of pain and in pain-related research in older persons.

Corticosteroid-binding globulin: a possible early predictor of infection in acute necrotizing pancreatitis

OBJECTIVE: Infected pancreatic necrosis is the main cause of death in patients with acute pancreatitis, and therefore its early prediction is of utmost importance. Endogenous cortisol metabolism plays a basic role both in the course of acute pancreatitis and in the process of infection. The purpose of this study was to analyze corticosteroid-binding globulin (CBG), total cortisol, calculated free cortisol and adrenocorticotropic hormone as potential early predictors in order to differentiate between infected pancreatic necrosis and sterile pancreatic necrosis in patients with acute pancreatitis. MATERIAL AND METHODS: Serum levels of CBG, total cortisol, calculated free cortisol, and plasma levels of adrenocorticotropic hormone were determined in 109 consecutive patients with acute pancreatitis. C-reactive protein was measured as the control parameter. Thirty-five patients developed necrotizing pancreatitis and 10 developed infection of the necrosis. Blood was monitored for 6 days after the onset of pain; 30 healthy individuals served as controls. RESULTS: Of all parameters only CBG showed a significant difference (p = 0.0318) in its peak levels measured in the first 48 h in patients with sterile (26.5 microg/ml, range 21.3-34.7) and infected (16.0 microg/ml, range 15.2-25.0) necrosis at a cut-off level of 16.8 microg/ml. That difference was further preserved for the first 6 days after onset of pain. CONCLUSIONS: In our group of patients, a decreased CBG level below 16.8 g/ml within the initial 48 h of acute pancreatitis was an early predictor of later infected pancreatic necrosis, with a positive predictive value of 100% and a negative predictive value of 87.5%.

Managing chronic whiplash associated pain with a combination of low-dose opioid (remifentanil) and NMDA-antagonist (ketamine)

The aim was to investigate the efficacy of a combination of low-dose remifentanil (REMI) and ketamine (KET) compared to the single drugs and placebo (P) on whiplash associated pain (WAD) in a double-blind, randomized, placebo-controlled, cross-over study. Twenty patients with chronic (>1 year) WAD were included. Four different drug combinations were tested in four sessions: placebo/placebo (P/P), placebo/remifentanil (P/REMI), ketamine/placebo (KET/P) and ketamine/remifentanil (KET/REMI). Target concentrations were 1 and 2ng/ml (stepwise) for remifentanil and 100ng/ml for ketamine. Habitual pain intensity was assessed on a visual analogue scale (VAS). Experimental pain was assessed with electrical stimulation (single and repeated) of tibialis anterior (TA) muscle, pressure pain algometry applied over infraspinatus (IS) and TA muscles and VAS scores after intramuscular hypertonic saline infusion in TA. KET/REMI significantly reduced habitual pain. KET/REMI infused at low REMI target concentration (1ng/ml) significantly elevated electrical intramuscular pain thresholds (single and repeated). Pain thresholds to electrical stimulation were similarly increased by both P/REMI and KET/REMI at 2ng/ml target concentration. Pressure pain thresholds were increased by both KET/REMI and P/REMI. VAS-scores after intramuscular saline were also similarly decreased by both REMI combinations. Seven out of 20 subjects were non-responders (<50% pain relief). No correlation was found between effects on spontaneous pain and experimental pain. KET/REMI showed an analgesic effect on habitual pain. Experimental pain was attenuated by both combinations containing the opioid, however, KET seemed to enhance the effect of REMI on electrical pain thresholds when a low REMI target concentration was used.

Ultrasound-guided blocks for the treatment of chronic pain

Ultrasound (US) is an emerging imaging technique in interventional pain management. The main advantages are the identification of soft tissues, vessels, and nerves, without exposing patients and personnel to radiation, the possibility to perform continuous imaging, and the visualization of the fluid injected in a real-time fashion. Possible applications are nerve blocks of the cervical and lumbar zygapophysial joints, stellate ganglion block, intercostal nerve blocks, occipital nerve blocks, blocks of the inguinal nerves, peripheral nerve blocks of the extremities, blocks of painful stump neuromas, caudal epidural injections, and injections of tender points. US may also be used for destructive procedures, such as cryoanalgesia, radiofrequency lesions, or chemical neurolysis. The increasing published data available suggest that US has a potential usefulness in interventional pain management, but also limitations. There is still a need for clinical trials investigating efficacy and safety of US-guided pain procedures. Until these studies are made, fluoroscopy or computed tomography remain the gold standard for most interventional pain procedures.

Effect of therapeutic exercise for hip osteoarthritis pain: results of a meta-analysis

OBJECTIVE: Recommendations for lower extremity osteoarthritis (OA) and exercise have been primarily based on knee studies. To provide more targeted recommendations for the hip, we gathered evidence for the efficacy of exercise for hip OA from randomized controlled trials. METHODS: A bibliographic search identified trials that were randomized, controlled, completed by >or=60% of subjects, and involved an exercise group (strengthening and/or aerobic) versus a non exercise control group for pain relief in hip OA. Two reviewers independently performed the data extraction and contacted the authors when necessary. Effect sizes (ES) of treatment versus control and the I(2) statistic to assess heterogeneity across trials were calculated. Trial data were combined using a random-effects meta-analysis. RESULTS: Nine trials met the inclusion criteria (1,234 subjects), 7 of which combined hip and knee OA; therefore, we contacted the authors who provided the data on hip OA patients. In comparing exercise treatment versus control, we found a beneficial effect of exercise with an ES of -0.38 (95% confidence interval [95% CI] -0.68, -0.08; P = 0.01), but with high heterogeneity (I(2) = 75%) among trials. Heterogeneity was caused by 1 trial consisting of an exercise intervention that was not administered in person. Removing this study left 8 trials (n = 493) with similar exercise strategy (specialized hands-on exercise training, all of which included at least some element of muscle strengthening), and demonstrated exercise benefit with an ES of -0.46 (95% CI -0.64, -0.28; P < 0.0001). CONCLUSION: Therapeutic exercise, especially with an element of strengthening, is an efficacious treatment for hip OA.

SFRP-4 abrogates Wnt-3a-induced beta-catenin and Akt/PKB signalling and reverses a Wnt-3a-imposed inhibition of in vitro mammary differentiation

ABSTRACT: BACKGROUND: Conserved Wnt ligands are critical for signalling during development; however, various factors modulate their activity. Among these factors are the Secreted Frizzled-Related Proteins (SFRP). We previously isolated the SFRP-4 gene from an involuting rat mammary gland and later showed that transgenic mice inappropriately expressing SFRP-4 during lactation exhibited a high level of apoptosis with reduced survival of progeny. RESULTS: In order to address the questions related to the mechanism of Wnt signalling and its inhibition by SFRP-4 which we report here, we employed partially-purified Wnt-3a in a co-culture model system. Ectopic expression of SFRP-4 was accomplished by infection with a pBabepuro construct. The co-cultures comprised Line 31E mouse mammary secretory epithelial cells and Line 30F, undifferentiated, fibroblast-like mouse mammary cells. In vitro differentiation of such co-cultures can be demonstrated by induction of the beta-casein gene in response to lactogenic hormones.We show here that treatment of cells with partially-purified Wnt-3a initiates Dvl-3, Akt/PKB and GSK-3beta hyperphosphorylation and beta-catenin activation. Furthermore, while up-regulating the cyclin D1 and connexin-43 genes and elevating transepithelial resistance of Line 31E cell monolayers, Wnt-3a treatment abrogates differentiation of co-cultures in response to the lactogenic hormones prolactin, insulin and glucocorticoid. Cells which express SFRP-4, however, are largely unaffected by Wnt-3a stimulation. Since a physical association between Wnt-3a and SFRP-4 could be demonstrated with immunoprecipitation/Western blotting experiments, this interaction, presumably owing to the Frizzled homology region typical of all SFRPs, explains the refractory response to Wnt-3a which was observed. CONCLUSION: This study demonstrates that Wnt-3a treatment activates the Wnt signalling pathway and interferes with in vitro differentiation of mammary co-cultures to beta-casein production in response to lactogenic hormones. Similarly, in another measure of differentiation, following Wnt-3a treatment mammary epithelial cells could be shown to up-regulate the cyclin D1 and connexin-43 genes while phenotypically they show increased transepithelial resistance across the cell monolayer. All these behavioural changes can be blocked in mammary epithelial cells expressing SFRP-4. Thus, our data illustrate in an in vitro model a mechanism by which SFRP-4 can modulate a differentiation response to Wnt-3a.

Natalizumab: targeting alpha4-integrins in multiple sclerosis

In 1992, it was shown that monoclonal antibodies blocking alpha(4)-integrins prevent the development of experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis (MS). As alpha(4)beta(1)-integrin was demonstrated to mediate the attachment of immune-competent cells to inflamed brain endothelium in experimental autoimmune encephalomyelitis, the therapeutic effect was attributed to the inhibition of immune cell extravasation and inflammation in the central nervous system. This novel therapeutic approach was rapidly and successfully translated into the clinic. The humanized anti-alpha(4)-integrin antibody natalizumab demonstrated an unequivocal therapeutic effect in preventing relapses and slowing down the pace of neurological deterioration in patients with relapsing-remitting MS in phase II and phase III clinical trials. The occurrence of 3 cases of progressive multifocal leukoencephalopathy in patients treated with natalizumab led to the voluntary withdrawal of the drug from the market. After a thorough safety evaluation of all patients receiving this drug in past and ongoing studies for MS and Crohn's disease, natalizumab again obtained approval in the US and the European Community. A treatment targeting leukocyte trafficking in MS has now re-entered the clinic. Further thorough evaluation is necessary for a better understanding of the risk-benefit balance of this new treatment option for relapsing MS. In this review, we discuss the basic mechanism of action, key clinical results of clinical trials and the emerging indication of natalizumab in MS.

Different patterns of Siglec-9-mediated neutrophil death responses in septic shock

Sialic-acid-binding immunoglobulin-like lectin (Siglec) 9 mediates death signals in neutrophils. The objective of this study was to determine the heterogeneity of neutrophil death responses in septic shock patients and to analyze whether these ex vivo data are related to the severity and outcome of septic shock. In this prospective cohort study, blood samples of patients with septic shock (n = 26) in a medical-surgical intensive care unit (ICU) were taken within 24 h of starting the treatment of septic shock (phase A), after circulatory stabilization (phase B), and 10 days after admission or at ICU discharge if earlier (phase C). Neutrophil death was quantified in the presence and absence of an agonistic anti-Siglec-9 antibody after 24 h ex vivo. In phase A, two distinct patterns of Siglec-9-mediated neutrophil death were observed: resistance to neutrophil death (n = 14; Siglec-9 nonresponders) and increased neutrophil death (n = 12; Siglec-9 responders) after Siglec-9 ligation compared with neutrophils from normal donors. Experiments using a pharmacological pan-caspase-inhibitor provided evidence for caspase-independent neutrophil death in Siglec-9 responders upon Siglec-9 ligation. There were no differences between Siglec-9 responders and nonresponders in length of ICU or hospital stay of survivors or severity of organ dysfunction. Taken together, septic shock patients exhibit different ex vivo death responses of blood neutrophils after Siglec-9 ligation early in shock. Both the resistance and the increased susceptibility to Siglec-9-mediated neutrophil death tend to normalize within 72 h after shock. Further studies are required to understand the role of Siglec-9-mediated neutrophil death in septic shock.