[Perioperative measures for prevention of phantom pain: an evidence-based approach to risk reduction]. / Perioperative Maßnahmen zur Prävention von Phantomschmerz: ein evidenzbasierter Ansatz zur Risikoreduktion.

Prevention of phantom limb pain is one of the biggest and still largely unsolved challenges in perioperative medicine. Despite many study efforts and optimization of postoperative pain treatment over the last 30 years, a significant reduction in the incidence of phantom limb pain has not been achieved. Current studies have also shown that at least 50% of patients develop phantom pain after 6 months. A possible approach could be to combine multiple synergistic interventions and implement them as a perioperative phantom pain management strategy bundle. In addition to regional anesthesia, NMDA antagonists, gabapentinoids, antidepressants and systemic lidocaine could play a relevant role. The aim of this pharmacological intervention was the modification of the pathophysiological changes in peripheral nerves and in the central nervous system after amputation.

[Background and current use of adjuvants for regional anesthesia : From research to evidence-based patient treatment]. / Hintergrund und aktueller Einsatz von Adjuvanzien für die Regionalanästhesie : Aus der Forschung in die evidenzbasierte Patientenversorgung.

The discovery of the local anaesthetic effect by blocking sodium ion channels was a milestone in anaesthesia but was soon limited by sometimes life-threatening toxic effects of the local anaesthetics. By developing novel local anaesthetics and also by adding so-called adjuvants, attempts have been made to limit these life-threatening events. This article focuses on the historic background and the current state of the use of these adjuvants for regional anaesthesia. Adding epinephrine, clonidine or dexmedetomidine, but only as a single dose, results in a faster onset, longer duration of action and increased intensity of neuronal blockade of regional anaesthesia. The benefits of adding sodium bicarbonate, on the other hand, are relatively minor and, therefore, clinically negligible. Although increasing evidence in the literature suggests an improvement and prolongation of the analgesic effect after axonal administration of opioids, which can also be given continuously, systemic effects are not fully ruled out due to the increased incidence of central side effects. The partial local anaesthetic effects of opioids cannot always be distinguished from opioid receptor-specific effects. Mechanistic studies postulate a functional coupling of opioid receptors in injured rather than in intact peripheral nerves. Recent studies have identified glucocorticoid and mineralocorticoid receptors predominantly on peripheral nociceptive nerve fibers. This is consistent with numerous clinical reports of a marked prolongation of the local anaesthetic effect. In addition to the known genomic effects of steroids that occur via a change in gene expression of pain-sustaining protein structures, faster non-genomic effects are also discussed, which occur via a change in intracellular signaling pathways. In summary, new insights into mechanisms and novel results from clinical trials will help the anaesthesiologist in the decision to use adjuvants for regional anaesthesia which, however, requires to weigh the individual patient's benefits against the risks.

[Antibiotic stewardship in a basic care hospital : A retrospective observational study]. / Antibiotic stewardship an einem Krankenhaus der Grund- und Regelversorgung : Eine retrospektive Observationsstudie.

BACKGROUND: In response to the global increase in antibiotic resistance, the concept of antibiotic stewardship (ABS) has become increasingly important in recent years. Several publications have demonstrated the effectiveness of ABS, mainly in university facilities. This retrospective observational study describes the implementation of ABS in a basic care hospital. MATERIAL AND METHODS: Following existing national guidelines, an ABS team was set up and measures were launched. These included: hospital guidelines, teaching, weekly antibiotic ward rounds and the restriction of definite substances. The preinterventional/postinterventional data analysis compared the use of antibiotics and blood culture sets as well as the development of resistance, infection with Clostridium difficile (CDI), costs, mortality and length of hospital stay. RESULTS: The measures introduced led to a significant and continuous decline in total antibiotic use of initially 43 recommended daily doses (RDD)/100 patient days (PD) to 31 RDD/100 PD (p < 0.001). The largest decrease was observed in second generation (2G) cephalosporins (-67.5%), followed by 3G cephalosporins (-52.7%), carbapenems (-42.0%) and quinolones (-38.5%). The resistance rate of E. coli to 3G cephalosporins in blood cultures decreased from 26% to 9% (p = 0.021). The rate of blood cultures taken increased from 1.8 sets/100 PD to 3.2 sets/100 PD (+77%, p < 0.001). The pathogen detection rate, defined as one count when a minimum of one sample taken in a day is positive, also increased significantly from 4.0/1000 PD to 6.8/1000 PD (p < 0.001). The ABS had no effect on the overall mortality, the mean dwell time, and the preintervention low CDI incidence. CONCLUSION: The preinterventional/postinterventional comparison showed a significant reduction in the overall consumption of antibiotics with a redistribution in favor of antibiotics with a lower resistance selection. At the same time, the resistance rate of E. coli decreased. The increase of the blood culture rate indicates the optimization of diagnostic procedures. This ABS program had to be established with reduced resources but this seems to have been compensated by the more personal contact addressing the care takers and short chain of commands, as is possible in smaller hospitals. Presumably, the structure of basic care hospitals is particularly suitable for concepts covering entire hospitals. Further clusters of randomized studies are necessary to confirm this.

[Treatment of fibromyalgia syndrome with gamma-hydroxybutyrate : A randomized controlled study]. / Die Behandlung des Fibromyalgiesyndroms mit Gamma-Hydroxybuttersäure : Eine randomisierte, kontrollierte Studie.

BACKGROUND: The etiology of fibromyalgia syndrome is not yet fully understood. Current hypotheses suggest a potential role of gamma-hydroxybutyrate (GHB) in influencing endocrinological abnormalities in patients with fibromyalgia. OBJECTIVE: The aim of the study was to investigate whether low dose GHB as a growth-hormone releasing substance reduces pain intensity and improves depressive mood, physical impairment and sleep quality in outpatients with fibromyalgia. Additionally, adverse events were recorded. MATERIAL AND METHODS: The pilot study was conducted in the outpatient clinic for pain at the clinic for anesthesiology and surgical intensive care of the Charité Universitätsmedizin Berlin. In the study 25 female patients with fibromyalgia according to the criteria of the American College of Rheumatology were randomized into 2 groups. Over 15 weeks patients of the intervention group received 25 mg/kg body weight oral GHB before going to bed and were compared with a placebo control group. In addition, all patients participated in operant behavioral pain treatment in a group setting. Dependent variables were pain intensity, depressive mood, physical impairment and quality of sleep. RESULTS: There were no group differences in the course of pain intensity (p = 0.61), depressive mood (p = 0.16), physical impairment (p = 0.25) and quality of sleep (p = 0.44); however, all symptoms improved across the groups from pretherapy to posttherapy. Low dose GHB did not increase growth hormone blood concentrations. The number of adverse events that were reported more than two times was similar in both groups. DISCUSSION: Administration of low dose GHB did not yield clinical improvements in female outpatients with fibromyalgia. General improvement in the course of treatment may have resulted from operant behavioral pain therapy. Future studies on GHB should control hypothetical risk factors for identification of non-responders.

Efficacy, tolerability, and safety of cannabinoids for chemotherapy-induced nausea and vomiting--a systematic review of systematic reviews.

BACKGROUND: There is growing public and legislative body support for the medical use of cannabis products, for example, for chemotherapy-induced nausea and vomiting (CINV), in Germany. METHODS: A comprehensive literature search until November 2015 was conducted in MEDLINE, DARE and Cochrane libraries for systematic reviews of randomized controlled trials (RCTs) comparing herbal or pharmaceutical cannabinoids (CB) versus placebo or conventional antiemetics for CINV. Outcomes were reduction of CINV for efficacy, drop-out rates due to adverse events for tolerability, and serious adverse events for safety. The methodology quality of the systematic reviews was evaluated by the tool assessment of multiple systematic reviews (AMSTAR). RESULTS: Six systematic reviews of RCTs included the pharmaceutical CBs dronabinol, levonantradol, and nabilone or whole plant extract (e.g., nabiximol) compared with placebo or conventional antiemetics. There was moderate quality evidence on the efficacy of CBs compared to placebo and conventional antiemetics for CINV. There was moderate quality evidence that pharmaceutical CBs were less tolerated and less safe than placebo and conventional antiemetics in CINV. One RCT examining whole plant extract was included into the systematic reviews. No RCT was found comparing CBs with neurokinine-1 receptor antagonists. CONCLUSIONS: With safe and effective antiemetics available, CBs cannot be recommended as first- or second-line therapy for CINV. Some guidelines recommend pharmaceutical CBs as third-line treatment in the management of breakthrough nausea and vomiting. Due to the lack of RCT data and safety concerns, herbal cannabis cannot be recommended for CINV.

[Incidence of constipation in patients with outpatient opioid therapy]. / Auftreten von Obstipation bei Patienten mit ambulanter Opioidtherapie.

BACKGROUND: Constipation is a common complication in patients with opioid therapy. Additionally, patient-related risk factors also contribute to the development of constipation and these factors have to be integrated into an individualized treatment plan. OBJECTIVE: The aim of this study was to assess the incidence of constipation in patients with opioid therapy in an outpatient setting and to analyze the risk factors that contribute to the development of constipation. MATERIAL AND METHODS: This retrospective cohort study was conducted in two university affiliated outpatient departments at the Charité hospital in Berlin. The trial included all consecutively treated patients with opioid therapy of at least 4 weeks duration. The study was conducted from January 2013 to August 2013. Constipation was defined according to the Rome III criteria. RESULTS: Out of 1166 screened patients, altogether 171 patients were included with a median duration of opioid therapy of 5 years. The most common diagnoses were back pain, musculoskeletal pain and neuropathic pain. In 14% of the treated patients symptoms of constipation were detected and another 35% needed laxatives for symptom control resulting in an overall incidence of constipation of 49%. The remaining 51% of the patients did not use any laxatives and did not experience symptoms of constipation. Age and dosing of opioid therapy significantly increased the risk of consipation but duration of opioid therapy was not related to the incidence of constipation. DISCUSSION: The incidence of constipation in this population remains high although a relevant number of patients were intermittently free of symptoms without using laxatives. An individualized therapy plan and patient education seem to be important elements to control opioid-associated constipation.

[Practice of regional anesthesia for chronic pain patients in specialized pain services : A nationwide survey in Germany]. / Praxis der regionalanästhesiologischen Behandlung chronischer Schmerzpatienten in der stationären und ambulanten Versorgung : Eine deutschlandweite Umfrage.

BACKGROUND: The prevalence of chronic pain has been estimated to be 19% in the European population and criteria for disabling chronic pain were found in approximately 7% of the German population. Clinical care for these patients is provided in ambulant and hospital-associated facilities. In this context, invasive interventions are part of the diagnosis and treatment of several specific diseases. Current data on the structure of clinical care based regional anesthesia for chronic pain patients in Germany are not available. OBJECTIVE: This study focused on the application and practice of interventional procedures in the context of pain management. MATERIAL AND METHODS: An internet-based survey addressing pain facilities and pain specialists in Germany was carried out. The response rate achieved 54%. RESULTS: Overall 79% of the pain therapists who responded included regional anesthesia techniques in the therapeutic spectrum in up to 25% of patients. The leading indications for invasive procedures were back pain and neuropathic pain. Two thirds of the therapists reported performing a series of blocks. A reduction of pain intensity of 30-50% was often reported as a sufficient criterion for the success of regional anesthesia interventions. Typically, approximately 40% of the chronic pain patients undergoing a series of blocks achieved sufficient pain relief which lasted most commonly for 12 weeks up to 6 months. CONCLUSION: This survey describes the current structures of specialized pain facilities for regional anesthesia in Germany including responses from predominantly anesthesiologists in a hospital-associated setting. In light of the limited evidence in the literature there is no consensus on the interventional therapeutic management of chronic pain. Especially the application of a series of blocks and the frequency as well as criteria to support continuing or terminating a series of regional anesthesia interventions are not sufficiently evaluated. This survey also gives an incentive for a possible revision of the existing practice in regional anesthesia in the context of multimodal therapy and currently existing guidelines in future clinical studies.

Computer-assisted decision support for changing practice in severe sepsis and septic shock.

Computer-assisted decision support systems (CDSS) are designed to improve infection management. The aim of this prospective, clinical pre- and post-intervention study was to investigate the influence of CDSS on infection management of severe sepsis and septic shock in intensive care units (ICUs). Data were collected for a total of 180 days during two study periods in 2006 and 2007. Of the 186 patients with severe sepsis or septic shock, 62 were stratified into a low adherence to infection management standards group (LAG) and 124 were stratified into a high adherence group (HAG). ICU mortality was significantly increased in LAG versus HAG patients (Kaplan-Meier analysis). Following CDSS implementation, adherence to standards increased significantly by 35%, paralleled with improved diagnostics, more antibiotic-free days and a shortened time until antibiotics were administered. In conclusion, adherence to infection standards is beneficial for patients with severe sepsis or septic shock and CDSS is a useful tool to aid adherence.

Retrospective Study on Ganglionic and Nerve Block Series as Therapeutic Option for Chronic Pain Patients with Refractory Neuropathic Pain.

Objective: Current recommendations controversially discuss local infiltration techniques as specific treatment for refractory pain syndromes. Evidence of effectiveness remains inconclusive and local infiltration series are discussed as a therapeutic option in patients not responding to standard therapy. The aim of this study was to investigate the effectiveness of infiltration series with techniques such as sphenopalatine ganglion (SPG) block and ganglionic local opioid analgesia (GLOA) for the treatment of neuropathic pain in the head and neck area in a selected patient group. Methods: In a retrospective clinical study, 4960 cases presenting to our university hospital outpatient pain clinic between 2009 and 2016 were screened. Altogether, 83 patients with neuropathic pain syndromes receiving local infiltration series were included. Numeric rating scale (NRS) scores before, during, and after infiltration series, comorbidity, and psychological assessment were evaluated. Results: Maximum NRS before infiltration series was median 9 (IQR 8-10). During infiltration series, maximum NRS was reduced by mean 3.2 points (SD 3.3, p < 0.001) equaling a pain reduction of 41.0% (SD 40.4%). With infiltration series, mean pain reduction of at least 30% or 50% NRS was achieved in 54.2% or 44.6% of cases, respectively. In six percent of patients, increased pain intensity was noted. Initial improvement after the first infiltration was strongly associated with overall improvement throughout the series. Conclusion: This study suggests a beneficial effect of local infiltration series as a treatment option for refractory neuropathic pain syndromes in the context of a multimodal approach. This effect is both significant and clinically relevant and therefore highlights the need for further randomized controlled trials.

Adherence to standard operating procedures is crucial for intensive care unit survival of elderly patients.

Elderly patients account for 42-52% of intensive care unit (ICU) admissions and for almost 60% of all ICU days in the USA and up to 50% receive inappropriate antibiotic treatment. The aim of this study was to evaluate whether adherence to Standard Operating Procedures (SOPs) reduced ICU mortality in an elderly population. The study included consecutive patients (n = 228) aged > or = 60 years with an ICU stay of > 72 h. SOPs were based on evidence-based medicine guidelines for diagnosis and treatment of infections, and on local resistance rates. According to preset indicators of quality management standards and assessment of different degrees of adherence, an implementation rate > 70% was considered adherent (high adherence group [HAG]) and < or = 70% was considered non-adherent (low adherence group [LAG]). Patients in the HAG (n = 137) had significantly reduced mortality compared with LAG patients (n = 91): 5.8% versus 19.8%, respectively. It was concluded that adherence to SOPs based on evidence-based medicine that consider local resistance rates for antibiotic treatment in elderly ICU patients is associated with a lower mortality rate.

Comparison of three models for sepsis patient discrimination according to PIRO: predisposition, infection, response and organ dysfunction.

BACKGROUND: Sepsis remains one of the most challenging burdens of critically ill patients. But for interventional studies significant heterogeneity remains in classifying patients. PIRO (Predisposition, Response, Infection and Organ dysfunction) has been introduced as innovative option for improved patient characterization. Aim of this study was to evaluate precision to predict hospital mortality of three different proposed PIRO classification systems. METHODS: Data were prospectively obtained data in five ICUs in a university hospital in Berlin, Germany including adult patients with sepsis. Three different scoring systems were compared using patient characteristics to classify the population according to all cause hospital mortality risk (Moreno- PIRO, Rubulotta- PIRO and Howell-PIRO). RESULTS: Two-hundred-seventy-eight sepsis patients were included and reclassified using different PIRO models. All cause hospital mortality was 16.2%. Hospital mortality increased with higher PIRO scores with odds ratios of 1.070 (95% CI 1.041-1.100) for Moreno-PIRO, 1.282 (95% CI 1.079-1.524) for Rubulotta-PIRO and 1.256 (95% CI 1.146-1.367) for Howell-PIRO. Area under the curves for Moreno-PIRO was 0.743 (95% CI: 0.687-0.793), for Rubulotta-PIRO 0.646 (95% CI: 0.587-0.702) and for Howell-PIRO 0.751 (95% CI: 0.696-0.801). Moreno-PIRO and Howell-PIRO were statistically different compared with Rubulotta-PIRO (P=0.046 and P=0.035). CONCLUSION: Proposed PIRO classifications demonstrated slight differences between models without prioritization of one approach and all seemed feasible for patient classification. Future PIRO-development is needed to straighten predisposition, infection, and especially the response category.

Observational clinical study on the effects of different dosing regimens on vancomycin target levels in critically ill patients: Continuous versus intermittent application.

Different dosing regimens for vancomycin are in clinical use: intermittent infusion and continuous administration. The intention of using these different dosing regimens is to reduce toxicity, to achieve target levels faster and to avoid treatment failure. The aim of this phase IV study was to compare safety and effectiveness in both administration regimens. The study was conducted in 2010 and 2011 in three postoperative intensive care units (ICUs) in a tertiary care university hospital in Berlin, Germany. Adult patients with vancomycin therapy and therapeutic drug monitoring were included. Out of 675 patients screened, 125 received vancomycin therapy, 39% with intermittent and 61% with continuous administration. Patients with continuous administration achieved target serum levels significantly earlier (median day 3 versus 4, p=0.022) and showed fewer sub-therapeutic serum levels (41% versus 11%, p<0.001). ICU mortality rate, duration of ICU stay and duration of ventilation did not differ between groups. Acute renal failure during the ICU stay occurred in 35% of patients with intermittent infusion versus 26% of patients with continuous application (p=0.324). In conclusion, continuous administration of vancomycin allowed more rapid achievement of targeted drug levels with fewer sub-therapeutic vancomycin levels observed. This might indicate that patients with more severe infections or higher variability in renal function could benefit from this form of administration.

Preoperative depression and hospital length of stay in surgical patients.

BACKGROUND: The association of depression and hospital length of stay (LOS) has rarely been examined in surgical patients outside of cardiovascular surgery. This study investigates whether clinically significant preoperative depression shows an independent association with LOS in patients from various surgical fields after adjusting for age, gender and important somatic factors. METHODS: A total of 2624 surgical patients were included in this prospective observational study. Data were collected before the preoperative anesthesiological examination within a computer-assisted psychosocial self-assessment including screening for depression (Center for Epidemiologic Studies Depression Scale, CES-D). Data on peri- and postoperative somatic parameters were obtained from the electronic patient management system of the hospital six months after the preoperative assessment. RESULTS: LOS of patients with clinically significant depression (N.=296; median: 5 days, interquartile range: 3-8 days) was longer than LOS of patients without depression (N.=2328; median: 4 days, interquartile range: 2-6 days) (P<0.001). A multivariate logistic regression model with the binary dependent variable 'above versus below or equal to the median LOS' revealed that the significant association between depression and LOS persisted (OR: 1.822 [95% CI 1.360-2.441], P<0.001) when simultaneously including the covariates age, gender, ASA classification, Charlson Comorbidity Index, surgical field and POSSUM operative severity rating. CONCLUSION: Data suggest that the association of depression and LOS is independent of the impact of age, gender, surgical field, preoperative physical health, severity of medical comorbidity and extent of surgical procedure. Integration of depression therapy into routine care of surgical patients might be an option to improve outcomes.

Long-term effect of computer-assisted decision support for antibiotic treatment in critically ill patients: a prospective 'before/after' cohort study.

OBJECTIVES: Antibiotic resistance has risen dramatically over the past years. For individual patients, adequate initial antibiotic therapy is essential for clinical outcome. Computer-assisted decision support systems (CDSSs) are advocated to support implementation of rational anti-infective treatment strategies based on guidelines. The aim of this study was to evaluate long-term effects after implementation of a CDSS. DESIGN: This prospective 'before/after' cohort study was conducted over four observation periods within 5 years. One preinterventional period (pre) was compared with three postinterventional periods: directly after intensive implementation efforts (post1), 2 years (post2) and 3 years (post3) after implementation. SETTING: Five anaesthesiological-managed intensive care units (ICU) (one cardiosurgical, one neurosurgical, two interdisciplinary and one intermediate care) at a university hospital. PARTICIPANTS: Adult patients with an ICU stay of >48 h were included in the analysis. 1316 patients were included in the analysis for a total of 12,965 ICU days. INTERVENTION: Implementation of a CDSS. OUTCOME MEASURES: The primary end point was percentage of days with guideline adherence during ICU treatment. Secondary end points were antibiotic-free days and all-cause mortality compared for patients with low versus high guideline adherence. MAIN RESULTS: Adherence to guidelines increased from 61% prior to implementation to 92% in post1, decreased in post2 to 76% and remained significantly higher compared with baseline in post3, with 71% (p=0.178). Additionally, antibiotic-free days increased over study periods. At all time periods, mortality for patients with low guideline adherence was higher with 12.3% versus 8% (p=0.014) and an adjusted OR of 1.56 (95% CI 1.05 to 2.31). CONCLUSIONS: Implementation of computerised regional adapted guidelines for antibiotic therapy is paralleled with improved adherence. Even without further measures, adherence stayed high for a longer period and was paralleled by reduced antibiotic exposure. Improved guideline adherence was associated with reduced ICU mortality. TRIAL REGISTRATION NUMBER: ISRCTN54598675.