Positive Treatment Expectancies Reduce Clinical Pain and Perceived Limitations in Movement Ability Despite Increased Experimental Pain: A Randomized Controlled Trial on Sham Opioid Infusion in Patients with Chronic Back Pain.

BACKGROUND: Increasing evidence for the efficacy of analgesic placebo effects in laboratory studies with healthy persons raises the question whether placebos could be used to improve the treatment of pain patients. Expectancies play a central role in shaping analgesic placebo but also nocebo effects. OBJECTIVES: We investigated to what extent a sham opioid infusion (saline solution) produces sustained clinically relevant placebo and nocebo effects in chronic back pain patients. METHODS: Fifty-nine patients received the sham opioid infusion applied via a large drain dressing and were compared to 14 control patients without intervention (natural history, NH) while experimental pain stimuli were applied. All subjects were told that the infusion would decrease pain although in rare cases pain increase would be possible (induction of expectancy). In addition, conditioning was introduced where the participants either experienced a decrease in experimental pain (n = 17; placebo conditioning), an increase (n = 21; nocebo conditioning), or no change (n = 21, no conditioning). RESULTS: Compared to the NH group, all infusion groups showed positive treatment expectancies and significantly (p < 0.001) reduced clinical back pain (primary outcome) and pain-related disability (secondary outcome, assessed by self-reported functional capacity and perceived impairment of mobility). Even the nocebo conditioned group experiencing increased experimental pain developed positive treatment expectancies followed by reduced pain experience. Positive treatment expectancies and relief in clinical back pain were significantly positively correlated (r = 0.72, p < 0.01). CONCLUSIONS: These findings suggest that it may be beneficial to explicitly shape and integrate treatment expectancies into clinical pain management.

[Cannabis in Parkinson's Disease: Hype or help?] / Cannabis bei Parkinson ­ Hype oder Heilmittel?

Cannabis buds and extracts as well as synthetic cannabinoids have been available on prescription to patients with severe diseases since March 2017, with the costs covered by health insurance companies.The prescription of medical marihuana is not restricted to specific symptoms and is therefore also valid for patients with Parkinson's disease. From a legal perspective, patients who are seriously ill even have the right to be treated with cannabis if standard treatment methods are unsuccessful or result in unbearable side effects. This also applies even if only a slight chance of noticeable improvement is predicted as a result of the cannabis treatment.Bearing this in mind and due to an intense media coverage of this topic, more and more patients with Parkinson's disease are requesting cannabis prescription, which is a challenging situation to their neurologists.This article provides an overview of the various cannabis products that can be prescribed, the different modes of administration and the available literature regarding motor- and non-motor symptoms in Parkinson's disease. Furthermore, the authors state their opinion on which indications cannabinoids could be useful in treating patients with Parkinson's disease or in which situation the patient could or even should be prescribed cannabinoids. Additionally, this article presents practical recommendations for the prescription of cannabinoids and patient counseling, e. g., on the effects of medical marijuana on driving capacity.

Single-dose Antibiotic Prophylaxis in Regional Anesthesia: A Retrospective Registry Analysis.

BACKGROUND: Catheter-related infection is a serious complication of continuous regional anesthesia. The authors tested the hypothesis that single-dose antibiotic prophylaxis is associated with a lower incidence of catheter-related infections. METHODS: Our analysis was based on cases in the 25-center German Network for Regional Anesthesia database recorded between 2007 and 2014. Forty thousand three hundred sixty-two surgical patients who had continuous regional anesthesia were grouped into no antibiotic prophylaxis (n = 15,965) and single-dose antibiotic prophylaxis (n = 24,397). Catheter-related infections in each group were compared with chi-square test after 1:1 propensity-score matching. Odds ratios (ORs [95% CI]) were calculated with logistic regression and adjusted for imbalanced variables (standardized difference more than 0.1). RESULTS: Propensity matching successfully paired 11,307 patients with single-dose antibiotic prophylaxis (46% of 24,397 patients) and with 11,307 controls (71% of 15,965 patients). For peripheral catheters, the incidence without antibiotics (2.4%) was greater than with antibiotic prophylaxis (1.1%, P < 0.001; adjusted OR, 2.02; 95% CI, 1.49 to 2.75, P < 0.001). Infections of epidural catheters were also more common without antibiotics (5.2%) than with antibiotics (3.1%, P < 0.001; adjusted OR, 1.94; 95% CI, 1.55 to 2.43, P < 0.001). CONCLUSIONS: Single-dose antibiotic prophylaxis was associated with fewer peripheral and epidural catheter infections.

Awake, sedated or anaesthetised for regional anaesthesia block placements?: A retrospective registry analysis of acute complications and patient satisfaction in adults.

BACKGROUND: Whether adults should be awake, sedated or anaesthetised during establishment of regional anaesthesia is still debated and there is little information on the relative safety of each. In paediatric practice, there is often little choice but to use sedation or anaesthesia as otherwise the procedures would be too distressing and patient movement would be hazardous. OBJECTIVE(S): The objective of this study was to evaluate complications related to central and peripheral regional block and patient satisfaction in awake, sedated and anaesthetised adult patients. DESIGN: A retrospective registry analysis. SETTING: The German Network of Regional Anaesthesia database was analysed between 2007 and 2012. PATIENTS: We included data of 42 654 patients and defined three groups: group I awake (n = 25 004), group II sedated (n = 15 121) and group III anaesthetised (n = 2529) for block placement. MAIN OUTCOME MEASURES: Odds ratios [OR; 95% confidence interval (CI)] were calculated with logistic regression analysis and adjusted for relevant confounders to determine the risk of block-related complications in sedated or anaesthetised patients compared with awake patients. RESULTS: Rates of local anaesthetic systemic toxicity were comparable between the groups [awake 0.02% (95% CI: 0.002 to 0.0375), sedated 0.02% (0.003 to 0.042) and anaesthetised 0% (0 to 0.12%)], as were the rates of pneumothorax [awake 0.035% (0 to 0.074), sedated 0% (0 to 0.002) and anaesthetised 0.2% (0 to 0.56)]. Considering peripheral nerve blocks, sedated patients had a decreased risk for multiple skin puncture [adjusted OR: 0.78 (95% CI: 0.71 to 0.85), premature termination [0.45 (0.22 to 0.91)], primary failure [0.58 (0.40 to 0.83)] and postoperative paraesthesia [0.35 (0.28 to 0.45)], but an increased risk for a bloody tap [1.82 (1.50 to 2.21)]. General anaesthesia increased the risk of a bloody tap [adjusted OR: 1.33 (95% CI: 1.01 to 1.78)] and multiple skin puncture [1.28 (1.12 to 1.46)], but decreased the risk for postoperative paraesthesia [0.16 (0.06 to 0.38)]. In neuraxial sites, sedation increased the risk for multiple skin puncture [adjusted OR: 1.18 (95% CI: 1.09 to 1.29)], whereas block placement under general anaesthesia decreased the risk for multiple skin puncture [0.53 (0.39 to 0.72)] and bloody tap but significantly increased the risk for postoperative paraesthesia related to a catheter [2.45 (1.19 to 5.02)]. Sedation was associated with a significant improvement in patient satisfaction. CONCLUSION: Sedation may improve safety and success of peripheral nerve block placement. Block placement under general anaesthesia in adults should be reserved for experienced anaesthesiologists and special situations.

Effects of thoracic epidural anesthesia on survival and microcirculation in severe acute pancreatitis: a randomized experimental trial.

INTRODUCTION: Severe acute pancreatitis is still a potentially life threatening disease with high mortality. The aim of this study was to evaluate the therapeutic effect of thoracic epidural anaesthesia (TEA) on survival, microcirculation, tissue oxygenation and histopathologic damage in an experimental animal model of severe acute pancreatitis in a prospective animal study. METHODS: In this study, 34 pigs were randomly assigned into 2 treatment groups. After severe acute pancreatitis was induced by intraductal injection of glycodesoxycholic acid in Group 1 (n = 17) bupivacaine (0.5%; bolus injection 2 ml, continuous infusion 4 ml/h) was applied via TEA. In Group 2 (n = 17) no TEA was applied. During a period of 6 hours after induction, tissue oxygen tension (tpO2) in the pancreas and pancreatic microcirculation was assessed. Thereafter animals were observed for 7 days followed by sacrification and histopathologic examination. RESULTS: Survival rate after 7 days was 82% in Group 1 (TEA) versus 29% in Group 2: (Control) (P <0.05). Group 1 (TEA) also showed a significantly superior microcirculation (1,608 ± 374 AU versus 1,121 ± 510 AU; P <0.05) and tissue oxygenation (215 ± 64 mmHg versus 138 ± 90 mmHG; P <0.05) as compared to Group 2 (Control). Consecutively, tissue damage in Group 1 was reduced in the histopathologic scoring (5.5 (3 to 8) versus 8 (5.5 to 10); P <0.05). CONCLUSIONS: TEA led to improved survival, enhanced microcirculatory perfusion and tissue oxygenation and resulted in less histopathologic tissue-damage in an experimental animal model of severe acute pancreatitis.

Observing treatment outcomes in other patients can elicit augmented placebo effects on pain treatment: a double-blinded randomized clinical trial with patients with chronic low back pain.

ABSTRACT: Clinical research on social observational learning (SoL) as an underlying mechanism for inducing expectancy and eliciting analgesic placebo effects is lacking. This double-blinded randomized controlled clinical trial investigated the influence of SoL on medication-augmenting placebo effects in 44 patients with chronic low back pain. Our hypothesis was that observing positive drug effects on pain and mobility in another patient could increase pain reduction and functional capacity. To test this, we compared the effects of observing positive treatment outcomes in a sham patient (the social learning group [SoLG]) vs hearing the same sham patient report neutral effects (the control group). In the SoLG, the sham patient told peers about pain reduction due to amitriptyline and demonstrated his improved mobility by bending forwards and sideways while he told the control group only that he was taking amitriptyline. The primary outcome was a reduction in clinical low back pain self-ratings. The secondary outcome was perceptions of pain-related disability. The exploratory outcome was mood and coping statements. Data collection occurred before and after the intervention and 2 weeks later. After the intervention, pain decreased in both groups (F [1, 41] = 7.16, P < 0.05, d = 0.83), with no difference between groups. However, the SoLG showed a significantly larger decrease in perceived disability (F [1, 41] = 5, P < 0.05, d = 0.63). The direct observation of patient with chronic low back pain of positive treatment outcomes in the sham patient seems to have enhanced the treatment effects while indirect verbal reports of reduced pain did not.

Impact of patient information leaflets on pain medication intake behavior: a pilot study.

INTRODUCTION: Patient information leaflets on pain medication primarily list side effects while positive effects and action mechanisms remain underrepresented. Nocebo research has shown that negative instructions can lower analgesic effects. OBJECTIVES: Research on information leaflets and their influence on mood, memory of side effects, and intake behavior of healthy participants is needed. METHODS: To determine the ratio of positive to negative phrases, 18 information leaflets of common, over-the-market analgesics were examined of which 1 was selected. In a randomized, controlled study design, 18 healthy participants read this leaflet while 18 control group participants read a matched, neutral leaflet of an electrical device. Collected data concerned the recall of positive and negative contents, mood, anxiety, and the willingness to buy and take the drug. RESULTS: All examined leaflets listed significantly more side effects than positive effects (t17 = 5.82, P < 0.01). After reading the analgesic leaflet, participants showed a trend towards more negative mood (F1,34 = 3.78, P = 0.06, ηp2 = 0.1), a lower intention to buy [χ2 (1, n = 36) = 12.5, P < 0.01], a higher unwillingness to take the medication [χ2 (1, n = 36) = 7.2, P < 0.01], and even a greater recall for side effects than positive effects (t17 = 7.47, P < 0.01). CONCLUSION: Reading the patient information leaflets can increase fear and lower the intention to buy and the willingness to take a pain medication.

Why Does Threshold Level Change in Transcranial Motor-evoked Potentials During Surgery for Supratentorial Lesions?

BACKGROUND: Rising threshold level during monitoring of motor-evoked potentials (MEP) using transcranial electrical stimulation (TES) has been described without damage to the motor pathway in the cranial surgery, suggesting the need for monitoring of affected and unaffected hemisphere. We aimed to determine the factors that lead to a change in threshold level and to establish reliable criteria for adjusting stimulation intensity during surgery for supratentorial lesions. MATERIALS AND METHODS: Between October 2014 and October 2015, TES-MEP were performed in 143 patients during surgery for unilateral supratentorial lesions in motor-eloquent brain areas. All procedures were performed under general anesthesia using a strict protocol to maintain stable blood pressure. MEP were evaluated bilaterally to assess the percentage increase in threshold level, which was considered significant if it exceeded 20% on the contralateral side beyond the percentage increase on the ipsilateral side. Patients who developed a postoperative motor deficit were excluded. Volume of subdural air was measured on postoperative magnetic resonance imaging. Logistic regression was performed to identify factors associated with the intraoperative recorded changes in threshold level. RESULTS: A total of 123 patients were included in the study. On the affected side, 82 patients (66.7%) showed an increase in threshold level, which ranged from 2% to 48% and 41 patients (33.3%) did not show any change. The difference to the unaffected side was under 20% in all patients. The recorded range of changes in the systolic and mean pressure did not exceed 20 mm Hg in any of the patients. Pneumocephalus was detected on postoperative magnetic resonance imaging scans in 87 patients (70.7%) and 81 of them (93.1%) had an intraoperative increase in threshold level on either sides. Pneumocephalus was the only factor associated with an increase in threshold level on the affected side (P<0.001), while each of pneumocephalus and length of the procedure correlated with a change in threshold level on the unaffected side (P<0.001 and 0.032, respectively). CONCLUSIONS: Pneumocephalus was the only factor associated with increase in threshold level during MEP monitoring without damaging motor pathway. Threshold level on the affected side can rise up to 48% without being predictive of postoperative paresis, as long as the difference between the increased threshold of the affected and unaffected side is within 20%. Changes in systolic or mean blood pressure within a range of 20 mm Hg do not seem to influence intraoperative MEP.

The impact of early goal-directed fluid management on survival in an experimental model of severe acute pancreatitis.

PURPOSE: Severe acute pancreatitis (SAP) remains a life-threatening disease with classic etiology of systemic inflammatory response and mortality between 30 and 50 %. The aim of the present study is to compare two different treatment strategies of goal-directed hemodynamic management and evaluate their impact on survival, microcirculation, tissue oxygenation, and histopathologic damage in acute pancreatitis in a prospective animal study. METHODS: Thirty-four domestic pigs were randomly assigned to two different treatment groups. After induction of acute pancreatitis, in group 1 volume administration was guided by central venous pressure (CVP >12 mmHg) and mean arterial pressure (MAP). In group 2, hemodynamic management was guided primarily by left-ventricular stroke volume variation (SVV <10 %), MAP, and cardiac output (CO). Treatment according to randomization was performed for 6 h, and tissue oxygen tension in the pancreas and pancreatic microcirculation were evaluated. Thereafter, animals were observed for 7 days and then sacrificed. Standardized tissue specimens were taken post mortem, and histopathologic scoring was performed. RESULTS: Survival after 7 days was 29.4 % in group 2 versus 11.8 % in group 1 (p < 0.05). Pancreatic oxygen tension (138.0 ± 89.5 mmHg versus 71.1 ± 35.3 mmHg; p < 0.05) and pancreatic microcirculation (1,209.9 ± 630 AU versus 732 ± 315 AU; p < 0.05) were significantly higher in group 2. Significantly less histopathologic damage within the pancreas could be analyzed post mortem in group 2. CONCLUSIONS: Goal-directed hemodynamic management guided by stroke volume variation led to improved survival, tissue oxygenation, and microcirculatory perfusion, as well as less histopathologic damage in an animal model of severe acute pancreatitis.