[Support of opioid rotation using online apps : Evaluation of applicability and comparison to the LONTS guidelines]. / Unterstützung der Opioidrotation mithilfe von Online-Apps : Evaluation der Anwendbarkeit und Vergleich mit der LONTS-Leitlinie.

BACKGROUND: Opioid rotation can be indicated due to drug side effects, drug interactions or inadequate effect of treatment with opioids. For the determination of the oral morphine equivalence, a practice tool has been published with the long-term use of opioids in chronic nontumor-related pain (LONTS) guidelines. In contrast, several apps are available that have not yet been evaluated. MATERIAL AND METHODS: Apps and web applications for opioid conversion were searched using Google Play Store®, iOS App Store® and the Google® search engine. German and English language apps with calculator functions were included. Using the apps, 16 test cases from clinical practice were calculated and the deviation from the recommendation of the LONTS guidelines was calculated. RESULTS: A total of 17 apps were identified, 11 named the origin of the algorithm and 3 of them defined the literature sources. None of the apps and web applications had a quality seal, and none could solve all cases. Deviations of the resulting oral morphine equivalents of up to 179% from the guideline-compliant conversion were identified and 4 apps warned for overdosing. CONCLUSION: Although the apps and web applications simplify conversion between opioids, there is high variance in conversion factors and sometimes a relevant deviation from evidence-based tables. Overall, there is a high risk of false opioid dosing.

Local infiltration analgesia versus peripheral nerve block anaesthesia in total knee arthroplasty: a pharmaco-economic comparison.

BACKGROUND: A superior analgesic method in perioperative pain-management of patients receiving total knee arthroplasty is the subject of controversial debate. Although higher cost-efficiency is claimed for the local infiltration analgesia (LIA), there is a lack of data on its costs compared to peripheral nerve block anaesthesia (PNBA). The goal of this study was to investigate the differences in immediate perioperative costs between the LIA and PNBA in treatment of patients receiving total knee arthroplasty. METHODS: The comparison was conducted based on a randomized controlled clinical trial examining 40 patients with elective, primary total knee arthroplasty (TKA, 20 patients with LIA and 20 patients with PNBA). The analysis included surgical case costs, anaesthesiological case costs, material, costs of postoperative opioid requirements and catheter review visits for patients receiving PNBA. RESULTS: The overall mean costs for the LIA-group were 4328.72€ and 4368.12€ for the PNBA (p = 0.851). While there was no statistically significant difference in surgical case costs, the anaesthesiological costs were lower with the LIA procedure (1370.26€ vs. 1542.45€, p = 0.048). Material costs in the LIA group were 4.18€/patient and 94.64€/patient with the PNBA. Costs for postoperative opioid requirements showed no statistically significant difference between the two procedures. CONCLUSIONS: There is no relevant difference in immediate perioperative costs between LIA and PNBA. Shorter induction times lead to lower anaesthesiological case costs with the LIA. Overall economic aspects seem to play a less important role for determining an adequate procedure for perioperative pain management. TRIAL REGISTRATION: The study was approved by the ethics-review-board of Charité Hospital Berlin (Ethikausschuss 4, Charité - Universitätsmedizin Berlin, on 16th February 2017) and registered with data safety authorities. Study patients provided written informed consent to participate in the trial. Study registry: ClinicalTrials.gov, NCT03114306 .

Female Patients with Pneumonia on Intensive Care Unit Are under Risk of Fatal Outcome.

Background and Objectives: The impact of sex on mortality in patients with pneumonia requiring intensive care unit (ICU) treatment is still a controversial discussion, with studies providing heterogeneous results. The reasons for sex differences are widespread, including hormonal, immunologic and therapeutic approaches. This study's aim was to evaluate sex-related differences in the mortality of ICU patients with pneumonia. Material and Methods: A prospective observational clinical trial was performed at Charité University Hospital in Berlin. Inclusion criteria were a diagnosis of pneumonia and a treatment period of over 24 h on ICU. A total of 436 mainly postoperative patients were included. Results: Out of 436 patients, 166 (38.1%) were female and 270 (61.9%) were male. Significant differences in their SOFA scores on admission, presence of immunosuppression and diagnosed cardiovascular disease were observed. Male patients were administered more types of antibiotics per day (p = 0.028) at significantly higher daily costs (in Euros) per applied anti-infective drug (p = 0.003). Mortalities on ICU were 34 (20.5%) in females and 39 (14.4%) in males (p = 0.113), before correcting for differences in patient characteristics using logistic regression analysis, and afterwards, the female sex showed an increased risk of ICU mortality with an OR of 1.775 (1.029-3.062, p = 0.039). Conclusions: ICU mortality was significantly higher in female patients with pneumonia. The identification of sex-specific differences is important to increase awareness among clinicians and allow resource allocation. The impact of sex on illness severity, sex differences in infectious diseases and the consequences on treatment need to be elucidated in the future.

Motor and functional outcome of selective dorsal rhizotomy in children with spastic diplegia at 12 and 24 months of follow-up.

BACKGROUND: Selective dorsal rhizotomy (SDR) in ambulatory children affected by cerebral palsy (CP) is a surgical treatment option to lower spasticity and thereby improve gait and ambulation. The aim of the current study is to investigate the outcome of children with respect to spasticity, muscle strength, and overall function after SDR. METHODS: All children who underwent SDR via a single-level laminotomy in the time period from January 2007 to April 2015 at our center were enrolled in this study. Within a standardized evaluation process, the following was assessed routinely pre-operatively and 12 and 24 months following surgery: extent of spasticity at hip adductors and hamstrings as characterized by the Modified Ashworth Scale (MAS), maximal muscle strength as characterized by the Medical Council Research Scale (MRC), overall function regarding ambulation as characterized by the Gross Motors Function Classification System (GFMCS), and overall function as characterized by the Gross Motor Function Measure (GMFM-88). RESULTS: Matching sets of pre- and post-operative assessments of the chosen outcome parameters were available for 109 of the 150 children who underwent SDR within the observation period. After 24 months, the MAS scores of hip adductors (n = 59) improved in 71% and 76% of children on the right and left side, respectively. In 20% and 19%, it remained unchanged and worsened in 9% and 5% of children on the right and left side, respectively (p < 0.00625). For hamstrings, the rates for the right and left sides were 81% and 79% improvement, 16% and 16% unchanged, and 4% and 5% worsened, respectively (p < 0.00625). Muscle strength of ankle dorsiflexion and knee extension significantly improved after 24 months. Overall function assessed by GMFM-88 improved significantly by 4% after 12 months (n = 77) and by 7% after 24 months (n = 56, p < 0.0001). CONCLUSIONS: The presented data underlines the benefit of SDR in a pediatric patient collective with bilateral spastic CP. The procedure resulted in an effective and permanent reduction of spasticity and improved overall function without causing relevant weakness of the lower extremities.

[Cannabis and cannabinoids for the treatment of acute and chronic pain]. / Cannabis und Cannabinoide zur Therapie akuter und chronischer Schmerzen.

Since the Act on the medical use of cannabis, at which cannabis-based medicines and cannabinoids became law, there has been an exponential increase in prescriptions for the acquisition of cannabis for medical purposes. The aim of this leading article is to compile and assess the currently available relevant clinical evidence for the use of cannabis and cannabinoids for treatment of acute and chronic pain. Based on the systematic literature review "Cannabis-Potential and risks (CAPRIS)" commissioned by the German Federal Ministry of Health and the recently published recommendations of the European Pain Federation EFIC, this article aims to give an orientation aid for the decision-making process in the clinical routine.

Frequency distribution in intraoperative stimulation-evoked EMG responses during selective dorsal rhizotomy in children with cerebral palsy-part 2: gender differences and left-biased asymmetry.

INTRODUCTION: Spinal reflexes reorganize in cerebral palsy (CP), producing hyperreflexia and spasticity. CP is more common among male infants, and gender might also influence brain and spinal-cord reorganization. This retrospective study investigated the frequency of higher-graded EMG responses elicited by electrical nerve-root stimulation during selective dorsal rhizotomy (SDR), prior to partial nerve- root deafferentation, considering not only segmental level and body side, but also gender. METHODS: Intraoperative neuromonitoring (IOM) was used in SDR to pinpoint the rootlets most responsible for exacerbated stimulation-evoked EMG patterns recorded from lower-limb muscle groups. Responses were graded according to an objective response-classification system, ranging from no abnormalities (grade 0) to highly abnormal (grade 4+), based on ipsilateral spread and contralateral involvement. Non-parametric analysis of data with repeated measures was primarily used in investigating the frequency distribution of these various EMG response grades. Over 7000 rootlets were stimulated, and the results for 65 girls and 81 boys were evaluated, taking changes in the composition of patient groups into account when considering GMFCS levels. RESULTS: The distribution of graded EMG responses varied according to gender, laterality, and level. Higher-graded EMG responses were markedly more frequent in the boys and at lower segmental levels (L5, S1). Left-biased asymmetry in higher-graded rootlets was also more noticeable in the boys and in patients with GMFCS level I. A close link was observed between higher-grade assessments and left-biased asymmetry. CONCLUSIONS: Detailed insight into the patient's initial spinal-neurofunctional state prior to deafferentation suggests that differences in asymmetrical spinal reorganization might be attributable to a hemispheric imbalance.

Local infiltration anaesthesia versus sciatic nerve and adductor canal block for fast-track knee arthroplasty: A randomised controlled clinical trial.

BACKGROUND: Local infiltration anaesthesia (LIA) was introduced as an innovative analgesic procedure for enhanced recovery after primary total knee arthroplasty (TKA). However, LIA has never been compared with analgesia based on an adductor canal catheter and a single-shot sciatic nerve block. OBJECTIVE: To evaluate two analgesic regimens for TKA comparing mobility, postoperative pain and patient satisfaction. DESIGN: Two-group randomised, controlled clinical trial. SETTING: Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Germany between April and August 2017. PATIENTS: Adults undergoing primary TKA under general anaesthesia were eligible for study participation. Exclusion criteria were heart insufficiency (New York Heart Association class >2), liver insufficiency (Child Pugh Score >B), evidence of diabetic polyneuropathy, severe obesity (BMI > 40 kg m), chronic opioid therapy for more than 3 months before scheduled surgery and allergy to local anaesthetics. INTERVENTIONS: Nerve block patients group (n=20) underwent surgery with two ultrasound-guided regional anaesthesia blocks: a single-shot sciatic nerve block with 20 ml of ropivacaine 0.75% combined with an adductor canal block with a catheter placed for less than 4 days with an infusion of ropivacaine 0.2% at a rate of 6 ml h. LIA patients (LIA group, n=20) received LIA of the knee capsule at the end of surgery with 150 ml of ropivacaine 0.2%. MAIN OUTCOME MEASURES: The primary endpoint was postoperative time to patient mobilisation (ability to walk) on the ward. RESULTS: Baseline characteristics were similar in each study group. Patients in both groups were mobilised to walk after TKA in similar time frames (LIA 24.0 h versus nerve block 27.1 h, 95% CI of difference -9.6 to 3.3 h). Maximum postoperative pain scores on exertion were higher in LIA patients with a mean 1.3 of 10 numerical rating scale points (95% CI 0.3 to 2.3, P = 0.010) as were intra-operative opioid requirements (LIA median 107 [IQR 100 to 268] mg versus nerve block median 78 [60 to 98] mg, P < 0.001). Patient satisfaction, postoperative oral morphine-equivalents and resting pain levels were comparable between groups. Anaesthesia induction time was reduced in LIA patients (LIA 10 min versus nerve block 35 min, 95% CI of difference 13 to 38 min, P < 0.001). CONCLUSION: Both analgesic regimens allow early mobilisation after TKA with high patient satisfaction. LIA shortened peri-operative time. Further research is required to optimise especially pain control during the later postoperative period with LIA. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03114306.

Observational clinical study on organ dysfunction associated with dosing of antibiotics in a Pediatric Intensive Care Unit.

BACKGROUND: Medication errors are of concern especially in pediatric patients. This study investigates impact of dosing errors of antibiotics on outcome in critically ill pediatric patients. METHODS: Retrospective study including all consecutive patients admitted to one university pediatric intensive care unit (PICU) in 2010 with length of PICU stay >24 hrs, age <18 years and antibiotic therapy. Antibiotic dosages were evaluated for compliance with recommended dosing individually adapted for bodyweight, age and organ function. Primary endpoint was organ dysfunction defined as occurrence of liver injury (LI) or acute kidney injury (AKI) after initiation of antibiotic therapy. AKI was defined as reduced estimated glomerular filtration below 50 mL/min or renal replacement therapy. LI was defined as more than two-fold elevation of liver enzymes. Additionally, duration of PICU stay, ventilation and all-cause PICU mortality were investigated. RESULTS: Altogether 305 patients were evaluated with 2577 patient PICU days and 4021 antibiotic dosages. Overall 38.6% of dosages were incorrect according to recommendations and were applied in 130 patients (low-adherence-group). 175 children received antibiotic dosing according to recommendations (high-adherence-group). Patients in the low-adherence-group showed a 7-fold increase in adjusted risk to develop new-onset organ dysfunction (95% CI: 2.1-26.4), needed longer median PICU treatment (7 versus 3 days, P<0.001) and prolonged duration of mechanical ventilation (8 versus 2 days, P<0.001). In subgroup analyses, organ dysfunction and PICU mortality were associated with non-adherence to recommendations. CONCLUSIONS: Adherence to a bodyweight- and age-adapted dosage-protocol is associated with less organ dysfunction and a more favorable clinical outcome in pediatric patients.

Effects of an Innovative Psychotherapy Program for Surgical Patients: Bridging Intervention in Anesthesiology--A Randomized Controlled Trial.

BACKGROUND: The stepped care program Bridging Intervention in Anesthesiology (BRIA) aims at motivating and supporting surgical patients with comorbid mental disorders to engage in psychosocial mental healthcare options. This study examined the efficacy of BRIA. METHODS: This randomized, parallel-group, open-label, controlled trial was conducted in the preoperative anesthesiological assessment clinics and surgical wards of a large university hospital in Germany. A total of 220 surgical patients with comorbid mental disorders were randomized by using the computer-generated lists to one of two intervention groups: BRIA psychotherapy sessions up to 3 months postoperatively (BRIA) versus no psychotherapy/computerized brief written advice (BWA) only. Primary outcome was participation in psychosocial mental healthcare options at month 6. Secondary outcome was change of self-reported general psychological distress (Global Severity Index of the Brief Symptom Inventory) between baseline and month 6. RESULTS: At 6-month follow-up, the rate of patients who engaged in psychosocial mental healthcare options was 30% (33 of 110) in BRIA compared with 11.8% (13 of 110) in BWA (P = 0.001). Number needed to treat and relative risk reduction were 6 (95% CI, 4 to 13) and 0.21 (0.09 to 0.31), respectively. In BRIA, Global Severity Index decreased between baseline and month 6 (P < 0.001), whereas it did not change significantly in BWA (P = 0.197). CONCLUSIONS: Among surgical patients with comorbid mental disorders, BRIA results in an increased engagement in subsequent therapy options and a decrease of general psychological distress. These data suggest that it is reasonable to integrate innovative psychotherapy programs into the context of interdisciplinary surgical care.

Impact of multiplex PCR on antimicrobial treatment in febrile neutropenia: a randomized controlled study.

Multiplex PCR (mPCR) directly from blood has been suggested as a promising method for rapid identification of pathogens causing sepsis. This study aimed to investigate whether mPCR has any impact on antimicrobial treatment. Hematological patients with febrile neutropenia were randomized into two groups. In the study group, mPCR was performed as an addition to standard diagnostics, and PCR finding was immediately communicated to the clinicians, thus being available for decision making. In the control group, clinicians were not aware of PCR result. PCR samples were collected simultaneously with clinically indicated blood culture specimens from peripheral vein and/or central venous catheter at fever onset and once again if fever persisted up to 72 h. Overall, 74 patients of the study group and 76 patients of the control group were enrolled and 253 samples collected. Therapy was changed to targeted antimicrobial therapy (AMT) in 12 patients (16.2%) in the study group and in 12 patients (15.8%) in the control group. For patients with changes, the median time to change to the targeted AMT was 21.4 h in the study group and 47.5 h in the control group (p = 0.018). In the study group, 57.1% (8/14) of changes to targeted AMT was due to PCR finding. PCR led to AMT change in 9.5% (7/74) of study group patients, i.e., in 33.3% (7/21) of patients who had positive PCR finding. There were no significant differences in patient outcomes (secondary endpoints). In conclusion, PCR method accelerates change to the targeted AMT in febrile neutropenic patients.

Standard operating procedures for antibiotic therapy and the occurrence of acute kidney injury: a prospective, clinical, non-interventional, observational study.

INTRODUCTION: Acute kidney injury (AKI) occurs in 7% of hospitalized and 66% of Intensive Care Unit (ICU) patients. It increases mortality, hospital length of stay, and costs. The aim of this study was to investigate, whether there is an association between adherence to guidelines (standard operating procedures (SOP)) for potentially nephrotoxic antibiotics and the occurrence of AKI. METHODS: This study was carried out as a prospective, clinical, non-interventional, observational study. Data collection was performed over a total of 170 days in three ICUs at Charité - Universitaetsmedizin Berlin. A total of 675 patients were included; 163 of these had therapy with vancomycin, gentamicin, or tobramycin; were >18 years; and treated in the ICU for >24 hours. Patients with an adherence to SOP >70% were classified into the high adherence group (HAG) and patients with an adherence of <70% into the low adherence group (LAG). AKI was defined according to RIFLE criteria. Adherence to SOPs was evaluated by retrospective expert audit. Development of AKI was compared between groups with exact Chi2-test and multivariate logistic regression analysis (two-sided P <0.05). RESULTS: LAG consisted of 75 patients (46%) versus 88 HAG patients (54%). AKI occurred significantly more often in LAG with 36% versus 21% in HAG (P = 0.035). Basic characteristics were comparable, except an increased rate of soft tissue infections in LAG. Multivariate analysis revealed an odds ratio of 2.5-fold for LAG to develop AKI compared with HAG (95% confidence interval 1.195 to 5.124, P = 0.039). CONCLUSION: Low adherence to SOPs for potentially nephrotoxic antibiotics was associated with a higher occurrence of AKI. TRIAL REGISTRATION: Current Controlled Trials ISRCTN54598675. Registered 17 August 2007.

[Frequency and barriers to the patient advanced directive and lasting power of attorney: findings from a prospective observation study in palliative care services]. / Häufigkeit und Barrieren bei Patientenverfügung und Vorsorgevollmacht: Erkenntnisse aus einer prospektiven Observationsstudie im palliativmedizinischen Dienst.

BACKGROUND: The advance directive and lasting power of attorney are instruments to strengthen patients' autonomy. A hospital-based palliative care consultation service can advise patients and family members about these instruments. This study investigates the need for such consultation among patients with life-limiting illness. METHODS: This prospective observational study on intensive and non-intensive care units includes patients with a request for palliative care consultation. Patient-related factors were evaluated for their possible association with the presence or absence of advance directives or power of attorney. In addition, focus group interviews with members of the palliative care consultation team were carried out to identify barriers which prevent patients from drawing up such documents. RESULTS: A total of 241 oncological and 53 non-oncological patients were included with a median age of 67 years; 69 (23%) patients were treated in the intensive care unit (ICU). Overall, 98 (33%) patients had advance directives, and 133 (45%) had determined a legal health care proxy in advance. A total of 52 patients died in hospital (17.7%). Only age and relationship status were associated with directives. In interviews, the following barriers were identified: information deficit, concern regarding discontinuation of treatment, loss of autonomy and wish to avoid a burden for the family. CONCLUSION: The majority in this severely ill patient population lack advance directives. In order to remove barriers, more effective information and counseling is required about such directives. In particular, guidance should include potential clinical situations in which such directives are potentially beneficial.

Factors Influencing Antibody Response to SARS-CoV-2 Vaccination.

Vaccination plays a key role in tackling the ongoing SARS-CoV-2 pandemic but data regarding the individual's protective antibody level are still pending. Our aim is to identify factors that influence antibody response following vaccination in healthcare workers. This single-center study was conducted at Evangelische Kliniken Gelsenkirchen, Germany. Healthcare workers were invited to answer a questionnaire about their vaccinations and adverse reactions. Subsequently, the level of anti-receptor binding domain (RBD) IgG antibody against SARS-CoV-2's spike protein through blood samples was measured. For statistics, we used a defined correlation of protection (CoP) and examined risk factors associated with being below the given CoP. A total of 645 employees were included and most were female (n = 481, 77.2%). A total of 94.2% participants had received two doses of vaccines (n = 587) and 12.4% (n = 720) had been infected at least once. Most common prime-boost regimen was BNT162b2 + BNT162b2 (57.9%, n = 361). Age (p < 0.001), days since vaccination (p = 0.007), and the homologous vaccination regimen with ChAdOx + ChAdOx (p = 0.004) were risk factors for the antibody level being below the CoP, whereas any previous COVID-19 infection (p < 0.001), the number of vaccines (p = 0.016), and physical complaints after vaccination (p = 0.01) were associated with an antibody level above the CoP. Thus, age, vaccination regimen, days since vaccination, and previous infection influence the antibody level. These risk factors should be considered for booster and vaccinations guidelines.

Behaviour-based pain scales: Validity and interrater reliability of BPS-NI and PAINAD-G on general wards.

BACKGROUND: Measuring pain intensity in patients unable to communicate is a challenge on general wards. Observation-based pain scoring tools have been used for patients with dementia or in critically ill intensive care unit (ICU) patients. However, there is no established or validated assessment tool for non-ICU patients without dementia related cognitive deficiencies who cannot communicate. The "Behavioural Pain Scale Non-Intubated" (BPS-NI) and the "Pain Assessment In Advanced Dementia-German" (PAINAD-G) are potential tools to fill this gap. METHODS: This study was performed with verbal non-ICU patients on general wards at Charité Berlin. Two assessors independently rated pain intensity using the BPS-NI and the PAINAD-G along with patients' self-ratings on the Numeric Rating Scale (NRS). The interrater-reliability of BPS-NI and PAINAD-G was calculated and ROC-analyses were performed to identify cut-off values for medium and intense pain for each score. Effectiveness was calculated using percentage agreement. In total, 126 patients were included into analysis. RESULTS: The BPS-NI showed substantial congruence in interrater-reliability (Cohens-Kappa 0.71), whereas the PAINAD-G showed moderate congruence (Kappa 0.48). Based on ROC-analyses, for medium pain levels a cut-off 4 (BPS-NI) or 2 (PAINAD-G) and for severe pain levels cut-off 5 (BPS-NI) and 3 (PAINAD-G) would result in good accordance with self-reported NRS for pain. CONCLUSION: The BPS-NI shows a good validity in measuring pain intensity in patients on general wards and may possibly be used for patients unable to communicate. Using defined cut-off values for BPS-NI and PAINAD-G, clinically relevant pain intensities in patients can reliably be detected. SIGNIFICANCE: Measuring the pain intensity in patients unable to communicate is a common challenge on general wards. This study assessed reliability and applicability BPS-NI and the PAINAD-G in a general ward setting. Furthermore, it provides cut-off values in order to estimate pain intensity and support analgesic response.

Influence of Cannabinoid Treatment on Trajectories of Patient-Related Outcomes in Chronic Pain: Pain Intensity, Emotional Distress, Tolerability and Physical Disability.

The treatment of chronic pain with cannabinoids is becoming more widespread and popular among patients. However, studies show that only a few patients experience any benefit from this treatment. It also remains unclear which domains are affected by cannabinoid treatment. Therefore, the present study is novel in that it explores the effects of cannabinoid treatment on four patient-related outcome measures (PROMs), and includes patients with chronic refractory pain conditions who have been given the option of cannabinoid treatment. A retrospective design was used to evaluate the impact of cannabinoid treatment on patients with refractory pain in two German outpatient pain clinics. The present study shows that pain intensity (mean relative reduction (-14.9 ± 22.6%), emotional distress (-9.2 ± 43.5%), pain-associated disability (-7.0 ± 46.5%) and tolerability of pain (-11 ± 23.4%)) improved with cannabinoid treatment. Interestingly, the trajectories of the PROMs seemed to differ between patients, with only 30% of patients responding with respect to pain intensity, but showing improvements in other PROMs. Although the mean treatment effects remained limited, the cumulative magnitude of change in all dimensions may affect patients' quality of life. In summary, a singular evaluation with pain intensity as the sole outcome does not cover the multidimensional effects of cannabinoids. Therefore, the treatment effects of cannabinoids should be evaluated with different PROMs.

Supplementing transcranial direct current stimulation to local infiltration series for refractory neuropathic craniocephalic pain: A randomized controlled pilot trial.

Background: Some patients with neuralgia of cranial nerves with otherwise therapy-refractory pain respond to invasive therapy with local anesthetics. Unfortunately, pain regularly relapses despite multimodal pain management. Transcranial direct current stimulation (tDCS) may prolong pain response due to neuro-modulatory effects. Methods: This controlled clinical pilot trial randomized patients to receive anodal, cathodal or sham-tDCS stimulation prior to local anesthetic infiltration. Pain attenuation, quality-of-life and side effects were assessed and compared with historic controls to estimate effects of tDCS stimulation setting. Results: Altogether, 17 patients were randomized into three groups with different stimulation protocols. Relative reduction of pain intensity in per protocol treated patients were median 73%, 50% and 69% in anodal, cathodal and sham group, respectively (p = 0.726). Compared with a historic control group, a lower rate of responders with 50% reduction of pain intensity indicates probable placebo effects (OR 3.41 stimulation vs. non-stimulation setting, NNT 3.63). 76.9% (n = 10) of tDCS patients reported mild side-effects. Of all initially included 17 patients, 23.5% (n = 4) withdrew their study participation with highest proportion in the cathodal group (n = 3). A sample size calculation for a confirmatory trial revealed 120 patients using conservative estimations. Discussion: This pilot trial does not support series of anodal tDCS as neuro-modulatory treatment to enhance pain alleviation of local anesthetic infiltration series. Notably, results may indicate placebo effects of tDCS settings. Feasibility of studies in this population was limited due to relevant drop-out rates. Anodal tDCS warrants further confirmation as neuro-modulatory pain treatment option.

Translation of Experimental Findings from Animal to Human Biology: Identification of Neuronal Mineralocorticoid and Glucocorticoid Receptors in a Sectioned Main Nerve Trunk of the Leg.

The activation of the mineralocorticoid (MR) and glucocorticoid (GR) receptors on peripheral sensory neurons seems to modify pain perception through both direct non-genomic and indirect genomic pathways. These distinct subpopulations of sensory neurons are not known for peripheral human nerves. Therefore, we examined MR and GR on subpopulations of sensory neurons in sectioned human and rat peripheral nerves. Real-time PCR (RT-PCR) and double immunofluorescence confocal analysis of MR and GR with the neuronal markers PGP9.5, neurofilament 200 (NF200), and the potential pain signaling molecules CGRP, Nav1.8, and TRPV1 were performed in human and rat nerve tissue. We evaluated mechanical hyperalgesia after intrathecal administration of GR and MR agonists. We isolated MR- and GR-specific mRNA from human peripheral nerves using RT-PCR. Our double immunofluorescence analysis showed that the majority of GR colocalized with NF200 positive, myelinated, mechanoreceptive A-fibers and, to a lesser extent, with peripheral peptidergic CGRP-immunoreactive sensory nerve fibers in humans and rats. However, the majority of MR colocalized with CGRP in rat as well as human nerve tissue. Importantly, there was an abundant colocalization of MR with the pain signaling molecules TRPV1, CGRP, and Nav1.8 in human as well as rat nerve tissue. The intrathecal application of the GR agonist reduced, and intrathecal administration of an MR agonist increased, mechanical hyperalgesia in rats. Altogether, these findings support a translational approach in mammals that aims to explain the modulation of sensory information through MR and GR activation. Our findings show a significant overlap between humans and rats in MR and GR expression in peripheral sensory neurons.

[Practice of perioperative phantom limb pain prevention in Germany: a nationwide survey]. / Praxis der perioperativen Prävention von Phantomschmerz: eine deutschlandweite Umfrage.

BACKGROUND: The prevalence of phantom limb pain after major amputation remains high and affected patients suffer from relevant impairments in the quality of life. Perioperative treatment strategies may prevent phantom limb pain. This study aims to assess the state of the perioperative anesthesiological pain management for major amputations. Furthermore, it analyzes potentials for optimization and barriers towards a better treatment of patients with amputations. MATERIAL AND METHODS: This online survey was distributed by the German Society of Anesthesiology and Intensive Care Medicine (DGAI) mailing list of anesthesiological consultants. It was approved by the Charité ethics board. RESULTS: Overall, 402 persons participated in this survey. Mostly, general anesthesia (85%), regional anesthesia (63%) and neuraxial anesthesia (49%) were performed in different combinations. Furthermore, 72% of participants reported using i.v. opioids postoperatively, mostly applied via patient-controlled analgesia (PCA). In contrast, preoperative regional anesthesia (74%) and gabapentinoids (67%) were seen as potential methods to improve treatment; however, barrier analysis revealed that treatment options are limited especially by organizational aspects and intrinsic patient factors. CONCLUSION: This survey describes the current practice of phantom limb pain prevention in Germany. It shows an unmet need for specialized perioperative pain treatment. As the evidence regarding treatment recommendations is limited, further research questions can be deduced from this study.