[Comparison of different prediction models for the occurrence of nausea and vomiting in the postoperative phase : A systematic qualitative comparison based on prospectively defined quality indicators]. / Vergleich verschiedener Vorhersagemodelle für das Auftreten von Übelkeit und Erbrechen in der postoperativen Phase : Ein systematischer qualitativer Vergleich anhand prospektiv definierter Qualitätsindikatoren.

BACKGROUND: Various prognostic prediction models exist for evaluating the risk of nausea and vomiting in the postoperative period (PONV). So far, no systematic comparison of these prognostic scores is available. METHOD: A systematic literature search was carried out in seven medical databases to find publications on prognostic PONV models. Identified scores were assessed against prospectively defined quality criteria, including generalizability, validation and clinical relevance of the models. RESULTS: The literature search revealed 62 relevant publications with a total of 81,834 patients which could be assigned to 8 prognostic models. The simplified Apfel score performed best, primarily because it was extensively validated. The Van den Bosch score and Sinclair score tied for second place. The simplified Koivuranta score was in third place. CONCLUSION: The qualitative analysis highlights the strengths and weaknesses of each prediction system based on predetermined standardized quality criteria.

Pharmacokinetic Characterisation and Comparison of Bioavailability of Intranasal Fentanyl, Transmucosal, and Intravenous Administration through a Three-Way Crossover Study in 24 Healthy Volunteers.

BACKGROUND: For more than 60 years, the synthetic opioid fentanyl has been widely used in anaesthesia and analgesia. While the intravenous formulation is primarily used for general anaesthesia and intensive care settings, the drug's high lipophilic properties also allow various noninvasive routes of administration. Published data suggest that intranasal administration is also attractive for use as intranasal patient-controlled analgesia (PCA). A newly developed intranasal fentanyl formulation containing 47 µg fentanyl, intravenous fentanyl, and oral transmucosal fentanyl citrate were characterised, and bioavailability was compared to assess the suitability of the intranasal formulation for an intranasal PCA product. METHODS: 27 healthy volunteers were enrolled in a single-centre, open-label, randomised (order of treatments), single-dose study in a three-period crossover design. The pharmacokinetics of one intranasal puff of fentanyl formulation (47 µg, 140 mL per puff), one short intravenous infusion of 50 µg fentanyl, and one lozenge with an integrated applicator (200 µg fentanyl) were studied, and bioavailability was calculated. Blood samples were collected over 12 hours, and plasma concentrations of fentanyl were determined by HPLC with MS/MS detection. RESULTS: 24 volunteers completed the study. The geometric mean of AUC0-tlast was the highest with oral transmucosal administration (1106 h ∗ pg/ml, CV% = 32.86), followed by intravenous (672 h ∗ pg/ml, CV% = 32.18) and intranasal administration (515 h ∗ pg/ml, CV% = 30.10). C max was 886 pg/ml (CV% = 59.38) for intravenous, 338 pg/ml (CV% = 45.61) for intranasal, and 310 pg/ml (CV% = 29.58) for oral transmucosal administration. t max was shortest for intravenous administration (0.06 h, SD = 0.056), followed by intranasal (0.21 h, SD = 0.078) and oral transmucosal administration (1.20 h, SD = 0.763). Dose-adjusted absolute bioavailability was determined to be 74.70% for the intranasal formulation and 41.25% for the oral transmucosal product. In total, 38 adverse events (AEs) occurred. Fourteen AEs were potentially related to the investigational items. No serious AE occurred. CONCLUSION: Pharmacokinetic parameters and bioavailability of the investigated intranasal fentanyl indicated suitability for its intended use as an intranasal PCA option.

Treatment of intraoperative hypotension with cafedrine/theodrenaline versus ephedrine : A prospective, national, multicenter, non-interventional study-the HYPOTENS trial.

BACKGROUND: Sympathomimetic drugs are a therapeutic cornerstone for the management of hypotensive states like intraoperative hypotension (IOH). While cafedrine/theodrenaline (C/T) is widely used in Germany to restore blood pressure in patients with IOH, more research is required to compare its effectiveness with alternatives such as ephedrine (E) that are more commonly available internationally. METHODS: HYPOTENS (NCT02893241, DRKS00010740) was a prospective, national, multicenter, open-label, two-armed, non-interventional study that compared C/T with E for treatment of IOH. We describe a prospectively defined cohort of patients ≥50 years old with comorbidities undergoing general anesthesia induced with propofol and fentanyl. Primary objectives were to examine treatment precision, rapidity of onset and the ability to restore blood pressure without relevant increases in heart rate. Secondary endpoints were treatment satisfaction and the number of required additional boluses or other accompanying measures. RESULTS: A total of 1496 patients were included in the per protocol analysis. Overall, effective stabilization of blood pressure was achieved with both C/T and E. Post-hoc analysis showed that blood pressure increase from baseline was more pronounced with C/T. Fewer additional boluses or other accompanying measures were required in the C/T arm. The incidence of tachycardia was comparable between groups. Post-hoc analysis showed that E produced dose-dependent elevated heart rate values. By contrast, heart rate remained stable in patients treated with C/T. Physicians reported a higher level of treatment satisfaction with C/T, with a higher proportion of anesthetists rating treatment precision and rapidity of onset as good or very good when compared with E. CONCLUSION: Neither drug was superior in restoring blood pressure levels; however, post-hoc analyses suggested that treatment is more goal-orientated and easier to control with C/T. Heart rate was shown to be more stable with C/T and fewer additional interventions were required to restore blood pressure, which could have contributed to the increased treatment satisfaction reported by anesthetists using C/T.

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta-analysis.

Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Quo Vadis PCA? A Review on Current Concepts, Economic Considerations, Patient-Related Aspects, and Future Development with respect to Patient-Controlled Analgesia.

This review assesses four interrelating aspects of patient-controlled analgesia (PCA), a long-standing and still widely used concept for postoperative pain management. Over the years, anaesthesiologists and patients have appreciated the benefits of PCA alike. The market has seen new technologies leveraging noninvasive routes of administration and, thus, further increasing patient and staff satisfaction as well as promoting safety aspects. Pharmaceutical research focuses on the reduction or avoidance of opioids, side effects, and adverse events although influence of these aspects appears to be minor. The importance of education is still eminent, and new educational formats are tested to train healthcare professionals and patients likewise. New PCA technology can support the implementation of efficient processes to reduce workload and human errors; however, these new products come with a cost, which is not necessarily reflected through beneficial budget impact or significant improvements in patient outcome. Although first steps have been taken to better recognize the importance of postoperative pain management through the introduction of value-based reimbursement, in most western countries, PCA is not specifically compensated. PCA is still an effective and valued technique for postoperative pain management. Although there is identifiable potential for future developments in various aspects, this potential has not materialized in new products.

A cross-sectional study on preoperative anxiety in adults.

OBJECTIVE: The main objective of this study was a detailed comparison of the level of anxiety about surgery and anesthesia. Other objectives included the assessment of the prevalence and intensity of preoperative anxiety. METHODS: This cross-sectional single-center survey used the validated Amsterdam anxiety and information scale (APAIS) and a modified numeric rating scale (mNRS) to assess preoperative anxiety, anxiety about surgery and anxiety about anesthesia. Prevalences and intensities of anxieties were predominantly analyzed descriptively. RESULTS: 3200 patients were enrolled and 3087 (57% females) were analyzed. 92.6% reported preoperative anxiety according to APAIS scores. The average total APAIS anxiety score (APAIS-A-T) was 9.9 (SD 3.6). 40.5% reported high anxiety (defined as APAIS-A-T > 10). Mean anxiety about surgery (APAIS-A-Su) was higher than mean anxiety about anesthesia (APAIS-A-An): 5.5 (SD 2.1) vs. 4.3 (SD 1.9), p < 0.0001. Accordingly, more patients were substantially more afraid (score difference > 2) of surgery (642, 20.8%, 95% CI 19.4-22.3) than of anesthesia (48, 1.6%, 95% CI 1.2-2.1). CONCLUSION: Preoperative anxiety is still very common among adult patients scheduled to undergo an elective procedure. Therefore, it should be evaluated routinely. Anxiety about surgery and anxiety about anesthesia differ in many patients. For this reason, anxiety about surgery and anxiety about anesthesia should be assessed separately. This would allow providing a more individualized support of patients to cope with their anxiety and could require particular attention by the surgeon or the anesthetist.

Echocardiographic imaging options in ovine research subjects.

OBJECTIVES: To determine the feasibility of acquiring quality transesophageal (TEE), epicardial (EE), and intracardiac (ICE) echocardiographic images in ovine subjects and to discuss the merits of each technique with a focus on ICE image acquisition. ANIMALS: Eleven male castrated Dorset adult sheep. METHODS: Transesophageal echocardiography was performed under general anesthesia. Epicardial echocardiography was performed as part of an open chest (thoracotomy or sternotomy) experiment. Subjects were recovered with permanent jugular vein indwelling catheter and ICE from this approach was described. Feasibility of each technique was qualitatively assessed based on subjective image quality from three images for each image plane in each sheep. RESULTS: Transesophageal echocardiography was technically challenging and did not provide adequate image quality for consistent interpretation. Epicardial echocardiography and ICE had more favorable results with ICE demonstrating unique benefits for post-operative serial monitoring. CONCLUSIONS: Epicardial echocardiography and ICE were effective imaging techniques. Epicardial echocardiography required the least specialized training but was considered to have limited feasibility due to its requirement for an open chest procedure. Even with the necessity for permanent indwelling jugular cannulation, ICE was the least invasive of the three imaging techniques and potentially the most practical approach for chronic studies by minimizing post-operative stress. Transesophageal echocardiography was not a feasible technique in this study.

Patient-controlled analgesia with remifentanil vs. alternative parenteral methods for pain management in labour: a Cochrane systematic review.

We aimed to assess the effectiveness of remifentanil used as intravenous patient-controlled analgesia for the pain of labour. We performed a systematic literature search in December 2015 (updated in December 2016). We included randomised, controlled and cluster-randomised trials of women in labour with planned vaginal delivery receiving patient-controlled remifentanil compared principally with other parenteral and patient-controlled opioids, epidural analgesia and continuous remifentanil infusion or placebo. The primary outcomes were patient satisfaction with pain relief and the occurrence of adverse events for mothers and newborns. We assessed risk of bias for each included study and applied the GRADE approach for the quality of evidence. We included total zero event trials, using a constant continuity correction of 0.01 and a random-effect meta-analysis. Twenty studies were included in the qualitative analysis; within these, 3713 participants were randomised and 3569 analysed. Most of our pre-specified outcomes were not studied in the included trials. However, we found evidence that women using patient-controlled remifentanil were more satisfied with pain relief than women receiving parenteral opioids (four trials, 216 patients, very low quality evidence) with a standardised mean difference ([SMD] 95%CI) of 2.11 (0.72-3.49), but were less satisfied than women receiving epidural analgesia (seven trials, 2135 patients, very low quality evidence), -0.22 (-0.40 to -0.04). Data on adverse events were sparse. However, the relative risk (95%CI) for maternal respiratory depression for patient-controlled remifentanil compared with epidural analgesia (three trials, 687 patients, low-quality evidence) was 0.91 (0.51-1.62). Compared with continuous intravenous infusion of remifentanil (two trials, 135 patients, low-quality evidence) no conclusion could be reached as all study arms showed zero events. The relative risk (95%CI) of Apgar scores less than 7 at 5 min after birth compared with epidural analgesia (five trials, 1322 participants, low-quality evidence) was 1.26 (0.62-2.57).

[PONV after strabismus surgery : Risk adapted prophylaxis?]. / PONV nach Strabismus-OP : Risikoadaptierte Prophylaxe?

BACKGROUND: Following strabismus surgery, patients frequently develop variable degrees of postoperative nausea and vomiting (PONV). These symptoms cause discomfort and result in serious complications such as intramuscular bleeding and subconjunctival hemorrhage. In children long lasting PONV can lead to and electrolyte imbalance and dehydration. A prolonged course of recovery is the consequence. For the hospital, PONV can also involve negative economic impacts because of a damaged public reputation of the institution. There is still an ongoing debate on wether prophylaxis of PONV is necessary and how the prophylaxis of PONV should be performed. On one hand, there are proponents of a liberal prophylaxis. These intend to treat almost all patients regardless of their individual risk for PONV. On the other hand, opponents point out that every medication has to be indicated individually. In their view, risk scores should be the base of a risk-adapted approach. OBJECTIVES: The aim of the study was to reduce the frequency of PONV by using an anesthetic technique adapted to the individual risk for PONV. Until now, all trials studying the efficiency of a score-based antiemetic prophylaxis were performed on adult patients. In this study, a risk-adapted approach was evaluated on children for the first time. PATIENTS AND METHODS: In 92 patients, the incidence of PONV was analyzed after strabismus surgery. Before surgery we evaluated the risk factors for PONV according to the POVOC score in children (n = 45, 49 %) and the Apfel's score in adults (n = 47, 51 %). Patients with 0-2 risk factors received a balanced anesthesia (n = 47, 51 %). Those with 3-4 risk factors were operated in total IV anesthesia (TIVA) with propofol (n = 45, 49 %). In addition, as an antiemetic prophylaxis, 0.15 mg/kg dexamethason and 0.1 mg/kg ondansetron were applied in the latter patients. we documented the symptoms and severity of PONV 2, 6 and 24 h after surgery by means of a standardized questionnaire for PONV (Wengritzky-Score). RESULTS: The incidence of PONV was 17 % (n = 16) in all of the patients. The incidence in low-risk patients receiving a BA without prophylaxis were 21 % in adults and 38 % in children. Of the patients at high risk for PONV receiving the multimodal antiemetic approach 8 % (adults) and 9 % (children) suffered from PONV. The combination of TIVA and antiemetics could reduce the incidence of PONV compared to the predicted values in a clinically relevant manner (OR = 0.26, KI: 0.76-0.87). CONCLUSION: The overall incidence could be reduced to a level below 20 %. Particularly in patients with a high risk of PONV, TIVA could clearly reduce the incidence. However, the incidence in patients with 2 risk factors is still high (30-39 %). Therefore, it is important to reconsider the effort involved with risk screening and individually adapting anesthesia. Risk stratification means a pre- and perioperative effort. Therefore, we advocate a more liberal approach for PONV prophylaxis.

Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis.

BACKGROUND: Improvement of postoperative pain and other perioperative outcomes remain a significant challenge and a matter of debate among perioperative clinicians. This systematic review aims to evaluate the effects of perioperative i.v. lidocaine infusion on postoperative pain and recovery in patients undergoing various surgical procedures. METHODS: CENTRAL, MEDLINE, EMBASE, and CINAHL databases and ClinicalTrials.gov, and congress proceedings were searched for randomized controlled trials until May 2014, that compared patients who did or did not receive continuous perioperative i.v. lidocaine infusion. RESULTS: Forty-five trials (2802 participants) were included. Meta-analysis suggested that lidocaine reduced postoperative pain (visual analogue scale, 0 to 10 cm) at 1-4 h (MD -0.84, 95% CI -1.10 to -0.59) and at 24 h (MD -0.34, 95% CI -0.57 to -0.11) after surgery, but not at 48 h (MD -0.22, 95% CI -0.47 to 0.03). Subgroup analysis and trial sequential analysis suggested pain reduction for patients undergoing laparoscopic abdominal surgery or open abdominal surgery, but not for patients undergoing other surgeries. There was limited evidence of positive effects of lidocaine on postoperative gastrointestinal recovery, opioid requirements, postoperative nausea and vomiting, and length of hospital stay. There were limited data available on the effect of systemic lidocaine on adverse effects or surgical complications. Quality of evidence was limited as a result of inconsistency (heterogeneity) and indirectness (small studies). CONCLUSIONS: There is limited evidence suggesting that i.v. lidocaine may be a useful adjuvant during general anaesthesia because of its beneficial impact on several outcomes after surgery.

A methodology for markerless genetic modifications in Azotobacter vinelandii.

AIMS: Efficient manipulation of multiple regions within a genome can be improved by counter-selection approaches. In this work, we sought to develop a method to manipulate Azotobacter vinelandii using a counter-selection approach based on the presence of the pyrF gene. METHODS AND RESULTS: A background uracil auxotroph of A. vinelandii was first constructed by deleting the pyrF gene coding orotidine-5'-phosphate decarboxylase. The pyrF gene and promoter were also incorporated together with an antibiotic marker to create a selection and counter-selection cassette to shuttle into various plasmids. The constructed cassette could then be removed using a plasmid lacking the pyrF gene via counter-selection resulting from the production of 5-fluorouracil. The process could be repeated multiple times using the same procedure for selection and counter-selection. Following completion, the pyrF gene may be reintroduced to the genome in its original location, leaving a completed strain devoid of any antibiotic markers. CONCLUSIONS: Utilization of the pyrF gene for counter-selection is a powerful tool that can be used effectively to make multiple gene deletions in A. vinelandii. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates the successful application of a counter-selection approach to yield markerless genetic modifications to A. vinelandii, which should be of interest for a range of applications in this important model bacterium.

Comparison of vestipitant with ondansetron for the treatment of breakthrough postoperative nausea and vomiting after failed prophylaxis with ondansetron.

BACKGROUND: Postoperative nausea and vomiting (PONV) is common; ondansetron is often used as prophylaxis or for breakthrough episodes. Vestipitant is a neurokinin 1 (NK-1) receptor antagonist that is effective for prophylaxis, but its efficacy for treating established PONV is unknown. This study was performed to evaluate the efficacy and safety of vestipitant, compared with ondansetron for the treatment of breakthrough PONV in patients who had already received prophylactic ondansetron before surgery. METHODS: A multicentre, randomized, single-blind (sponsor-open), parallel group study. Of 527 surgical patients, 130 (25%) had breakthrough PONV and were equally randomized to one of six i.v. doses of vestipitant (4-36 mg) or ondansetron 4 mg. The primary endpoint was the rate of patients exhibiting complete response, defined as no emesis and no further rescue medication from 10 min after infusion up to 24 h after surgery or hospital discharge. RESULTS: All doses of vestipitant were non-inferior to ondansetron in treating PONV after failed prophylaxis with ondansetron. However, vestipitant was superior to ondansetron in decreasing episodes of postoperative emesis and retching. The complete response rate analysis using Bayesian model averaging indicated that no vestipitant dose was superior to ondansetron. Nausea numerical rating scale scores and the times-to-PONV or discharge were similar between the vestipitant and ondansetron treatment groups. CONCLUSIONS: Although overall efficacy was non-inferior between vestipitant and ondansetron, the rate of emesis was lower with vestipitant. These data suggest that vestipitant may be a useful agent for the management of PONV, similar to other NK-1 antagonists. CLINICAL TRIAL REGISTRATION: NCT01507194.

Microcin MccPDI reduces the prevalence of susceptible Escherichia coli in neonatal calves.

AIMS: Microcin MccPDI-producing Escherichia coli have a fitness advantage in dairy calves. For this project, we determined whether MccPDI is responsible for the in vivo fitness advantage, which is a necessary condition before MccPDI strains can be considered viable candidates for inhibiting pathogenic serovars of E. coli. METHODS AND RESULTS: Neonatal calves were coinoculated with either MccPDI-producing E. coli or MccPDI-knockout mutants in conjunction with a susceptible strain. After 6 days, the MccPDI-producing E. coli-25 strain clearly dominated the E. coli-186 susceptible strain in the inoculated calves (P = 0·003). MccPDI-producing E. coli composed a higher log percentage of the total population of lactose-fermenting bacteria in the faeces (5·51 log CFU per 8·03 log CFU) compared with the knockout strain (2·6 log CFU per 8·23 log CFU) (P = 0·01), and it was more consistently recovered from the lower gastrointestinal tract at the time of necropsy (P = 0·01). CONCLUSION: Our findings support the hypothesis that MccPDI is functional in vivo and it is most likely responsible for a fitness advantage in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: MccPDI-producing E. coli strongly inhibit pathogenic E. coli strains in vitro. We show herein that MccPDI functions in vivo, and thus, these strains may be candidate probiotics against pathogenic strains of E. coli.

[Premedication visits in departments of anesthesiology in Hessen. Compilation of organizational and performance portfolios]. / Prämedikationsvisiten der anästhesiologischen Fachabteilungen in Hessen. Statuserfassung des Organisations- und Leistungsportfolios.

BACKGROUND: Many anesthesia departments operate a pre-anesthesia assessment clinic (PAAC). Data regarding organization, equipment and structure of such clinics are not yet available. Information about modern anesthesiology techniques and procedures contributes to a reduction in emotional stress of the patients but such modern techniques often require additional technical hardware and costs and are not equally available. AIM: This survey examined the current structures of PAAC in the state of Hessen, demonstrated current concepts and associated these with the performance and the portfolio of procedures in these departments. MATERIAL AND METHODS: An online survey was carried out. Data on structure, equipment, organization and available methods were compiled. In addition, anesthesia department personnel were asked to give individual subjective attitudes toward the premedication work. RESULTS: Of the anesthesia departments in Hessen 84 % participated in the survey of which 91 % operated a PAAC. A preoperative contact with the anesthesiologist who would perform anesthesia existed in only 19 % of the departments. Multimedia processing concepts for informed consent in a PAAC setting were in general rare. Many modern procedures and anesthesia techniques were broadly established independent of the hospital size. Regarding the individual and subjective attitudes of anesthetists towards the work, the psychological and medical importance of the pre-medication visit was considered to be very high. CONCLUSION: The PAACs are now well established. This may make economic sense but is accompanied by an anonymization of care in anesthesiology. The high quality, safety and availability of modern anesthesiology procedures and monitoring concepts should be communicated to patients all the more as an expression of trust and high patient safety. These factors can be facilitated in particular by multimedia tools which have as yet only been sparsely implemented in PAACs.

I.V. APD421 (amisulpride) prevents postoperative nausea and vomiting: a randomized, double-blind, placebo-controlled, multicentre trial.

BACKGROUND: Postoperative nausea and vomiting (PONV) remain significant clinical problems for patients, especially nausea. The D2-antagonist droperidol was popular for prophylaxis until safety concerns limited its use. In early testing, APD421 (amisulpride for i.v. injection), a D2/D3-antagonist, has shown promising antiemetic efficacy at very low doses. We conducted a randomized, double-blind, dose-finding study to investigate APD421 in PONV prophylaxis. METHODS: Adult surgical patients with ≥2 Apfel risk factors for PONV undergoing surgery expected to last ≥1 h and receiving standard inhalation anaesthesia were randomized to receive placebo or one of three doses of APD421 (1, 5, or 20 mg) as a single i.v. administration at anaesthesia induction. The primary endpoint was PONV (vomiting/retching or antiemetic rescue) in the 24 h period after surgery. RESULTS: Two hundred and fifteen patients received study drug, 92% female and 60% with ≥3 risk factors. Groups were well balanced for baseline characteristics and risk factors. The PONV incidence was 37/54 [69%; 90% confidence interval (CI), 57-79%] in the placebo group; 28/58 (48%; 90% CI, 37-60%) with 1 mg APD421 (P=0.048); 20/50 (40%; 90% CI, 28-53%) with 5 mg (P=0.006); and 30/53 (57%; 90% CI, 44-68%) with 20 mg (P>0.1). APD421 at 5 mg also significantly improved vomiting, rescue medication use, and nausea rates. The safety profile of APD421 was similar to that of placebo at all doses, with no significant central nervous system (CNS) or cardiac side-effects. CONCLUSIONS: APD421 given i.v. before surgery is safe and effective at reducing PONV in moderate/high-risk adult surgical patients. The optimal dose tested was 5 mg.

[On preoperative risk evaluation of adult patients before elective non-cardiac surgery: results of a survey on clinical practice in the Federal State of Hessen]. / Zur präoperativen Risikoevaluation erwachsener Patienten vor elektiven, nichtkardiochirurgischen Eingriffen: Ergebnisse einer Befragung zur klinischen Praxis im Bundesland Hessen.

BACKGROUND: The German Societies of Anesthesiology and Intensive Care Medicine, Internal Medicine and Surgery have recently published for the first time joint recommendations for the evaluation of adult patients prior to elective non-cardiac surgery. In these recommendations indications for preoperative diagnostic procedures were critically revised and updated. It was unclear to what extent these recommendations were known among German anesthesiologists, how the recommendations were perceived and to what extent they were put into practice. The indications of five common diagnostic procedures in the context of the preoperative evaluation were also unknown. METHODS: Three months after publication of the recommendations, all anesthesiologists employed at hospitals in the state of Hessen were requested to take part in an online survey (OS). In the first part of the OS participants were asked about familiarity with the recommendations, opinions concerning the utility of the recommendations and to what extent they were implemented. In the second part of the OS participants were questioned in general and in the context of two common case scenarios about indications for electrocardiograms (ECG), chest radiographs (chest x-ray), echocardiograms, spirometry and extended cardiac diagnostics, such as stress ECG. In addition, participants of the OS were requested to take part in an interview survey (IS) addressing the same topics. The purpose of the IS was to detect any bias caused by the anonymous character of the OS which could lead to an overestimated self-assessment. Answers of the IS were not compared to the results of the corresponding answers given online by the same anesthesiologist but only analyzed together with the other results of the IS for comparison with the results of the OS. RESULTS: Of the contacted anesthesiologists 396 (29 %) took part in the OS of which 100 took part in the IS. According to the OS 30 % were familiar and 34 % were partially familiar with the recommendations, 20 % just knew that recommendations had been published and 16 % did not even know about the publication. The corresponding results of the IS were 16 %, 36 %, 28 % and 20 %, respectively. Of the participants 90 % (OS) and 89 % (IS) considered the recommendations at least to be predominantly reasonable and useful and 66 % (OS) of the participants tried to implement or at least to partially implement the recommendations (IS only 33 %). Concerning the indications for the different diagnostic procedures, the results of the OS showed that hospital guidelines (44 %) and patient age (32 %) were the most frequent indications for a preoperative ECG. Hospital guidelines (40 %) and own judgement (39 %) were the most common indications for a preoperative chest x-ray and patient age still accounted for 18 % of the indications. In contrast, echocardiography (67 %), spirometry (61 %) and extended cardiac diagnostics (70 %) were primarily indicated based on own judgement. However, reasons given in this context were frequently (77 %) not in agreement with the recommendations. Comparing the results of the OS to those of the IS with respect to the indications of the different diagnostic procedures for the common case scenarios showed a varying degree of consistency with the recommendations. In both cases responses to the IS concerning the indications for the different diagnostic procedures were mostly in accordance with the recommendations compared to answers obtained in the OS. Indications for the chest x-ray showed the worst degree of consistency with the recommendations. CONCLUSIONS: Corresponding to the high significance of local standards for the decision of indicating preoperative diagnostic procedures, the development of local standards that are in agreement with the recommendations seems to be a reasonable way to facilitate the implementation of the recommendations.

[Hypoxemia after general anesthesia]. / Hypoxämie nach Allgemeinanästhesie.

BACKGROUND: Studies conducted shortly after the implementation of pulse oximetry (PO) into clinical practice 20-25 years ago revealed that many patients breathing room air during transfer from the operating room (OR) to the post-anesthesia care unit (PACU) directly after general anesthesia (GA) had a peripheral oxygen saturation (S(p)O(2)) below 90%. Moreover, it was shown that the detection of hypoxemia by clinical criteria is extremely unreliable. Meanwhile, the use of PO has become part of the obligatory standard monitoring during GA in Germany and many other countries. Likewise, the use of PO is standard care in the PACU although there are no official recommendations. However, for the time period in between, i.e. immediately after GA during transportation of patients from the OR to the PACU, monitoring of the S(p)O(2) in patients breathing room air is neither obligatory in Germany nor are there any official recommendations or guidelines in this respect. Given the introduction of shorter acting anesthetic agents within the last 25 years, the main goal of this study was to explore whether the incidence of hypoxemia in the immediate period after GA is still so high. Additional aims of this study were to examine whether the detection of hypoxemia based on clinical criteria can be confirmed to be very unreliable, what the risk factors for hypoxemia following GA are and how common it is in Germany to transport patients from the OR to the PACU without PO and supplemental oxygen. METHODS: In a prospective observational study 970 patients who underwent a broad spectrum of elective surgery under GA in a university hospital setting were included. The S(p)O(2) was measured at the end of the transfer from the OR to the PACU immediately after the anesthetist who had taken care of the patient during the operation had estimated the S(p)O(2). The association between biometric, surgical and anesthesiological variables on the one hand and hypoxemia as well as a decrease of S(p)O(2) on the other hand were studied using multivariate methods. Finally, a survey including all university hospitals was carried out to find out about the use of PO and oxygen during patient transfer from the OR to the PACU. RESULTS: Of the 959 patients who were eligible for analysis 17% had a S(p)O(2) < 90% and 6.6% a S(p)O(2) < 85%. Hypoxemia was not recognized in 82% of the patients in whom an assessment based on clinical grounds was carried out. Variables with an independent influence on hypoxemia and decrease of S(p)O(2) were as follows: saturation before induction of GA, body mass index, age, American Society of Anesthesiologists (ASA) physical status, difference between maximum and minimum inspiratory pressure, mode of ventilation, the choice of opioid and muscle relaxant as well as the use of nitrous oxide. Patient-dependent risk factors had the strongest impact on hypoxemia. In about 80% of the university hospitals neither PO nor supplemental oxygen is used during transportation of the patient from the OR to the PACU. CONCLUSIONS: The use of opioids and relaxants with short duration of action may have favorable effects on preventing hypoxemia and decreases of S(p)O(2). These measures will, however, not be sufficient to solve this problem because the highest risk factors for hypoxemia are patient-related. Despite knowing risk factors for oxygen desaturation, it is currently not possible to reliably predict which patients will become hypoxemic or have a decrease of S(p)O(2). Therefore, transportation of patients breathing room air from the OR to the PACU directly after GA without use of PO or supplemental oxygen seems to be questionable in terms of patient safety.

Ultrasound guidance for neuraxial analgesia and anesthesia in obstetrics: a quantitative systematic review.

PURPOSE: The aim of this quantitative systematic review was to assess the efficacy and safety of ultrasound-guided neuraxial blocks in obstetric analgesia and anesthesia. MATERIALS AND METHODS: A systematic search for clinical trials investigating the efficacy and safety of ultrasound-assisted neuraxial blocks in comparison to any other technique was performed in MEDLINE, EMBASE, CINAHL and CENTRAL. Relative risks (RR) were calculated for dichotomous data (e. g. number of patients with vascular punctures), and mean differences (MD) were calculated for continuous outcomes (e. g. number puncture attempts), along with the respective 95 % confidence intervals (95 % CI). RESULTS: Six clinical trials (published between 2001 and 2009) including the data of 659 patients satisfied the inclusion criteria. Ultrasound-facilitated neuraxial blocks required a lower number of puncture attempts (MD: -0.92; 95 % CI: -1.11 to -0.74; p < 0.00001) and fewer puncture levels (MD: -0.2; 95 % CI: -0.31 to -0.1; p = 0.0002) in comparison with the more conventional loss of resistance. The success rate with the first attempt under ultrasound guidance in supposedly difficult patients was 71 % in comparison to 20 % using a conventional technique. Patients receiving ultrasound-assisted neuraxial blocks had a lower rate of procedure-related complications (post-dural puncture headache, spinal or vascular puncture). CONCLUSION: There is some evidence that ultrasound guidance may improve the efficacy and safety of neuraxial blocks in obstetrics. If technical difficulties are anticipated, ultrasound may lower the rate of procedure-related adverse events.