Adiposity associated DNA methylation signatures in adolescents are related to leptin and perinatal factors.

Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated with concurrent adiposity measures and examined whether these were associated with hsCRP, adipokines, and early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants at 17 years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) associated with body mass index (BMI), 10 with waist circumference (WC) and 9 with subcutaneous fat thickness. DmCpGs within Ras Association (RalGDS/AF-6), Pleckstrin Homology Domains 1 (RAPH1), Musashi RNA-Binding Protein 2 (MSI2), and solute carrier family 25 member 10 (SLC25A10) are associated with both BMI and WC. Validation by pyrosequencing confirmed these associations and showed that MSI2 , SLC25A10 , and RAPH1 methylation was positively associated with serum leptin. These were  also associated with the early environment; MSI2 methylation (ß = 0.81, p = 0.0004) was associated with pregnancy maternal smoking, SLC25A10 (CpG2 ß = 0.12, p = 0.002) with pre- and early pregnancy BMI, and RAPH1 (ß = -1.49, p = 0.036) with gestational weight gain. Adjusting for perinatal factors, methylation of the dmCpGs within MSI2, RAPH1, and SLC25A10 independently predicted BMI, accounting for 24% of variance. MSI2 methylation was additionally associated with BMI over time (17 years old ß = 0.026, p = 0.0025; 20 years old ß = 0.027, p = 0.0029) and between generations (mother ß = 0.044, p = 7.5e-04). Overall findings suggest that DNA methylation in MSI2, RAPH1, and SLC25A10 in blood may be robust markers, mediating through early life factors.

Blood and nasal epigenetics correlate with allergic rhinitis symptom development in the environmental exposure unit.

BACKGROUND: Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis (AR). Our aim was to examine genome-wide epigenetic changes induced by controlled pollen exposure in the environmental exposure unit (EEU). METHODS: 38 AR sufferers and eight nonallergic controls were exposed to grass pollen for 3 hours on two consecutive days. We interrogated DNA methylation at baseline and 3 hours in peripheral blood mononuclear cells (PBMCs) using the Infinium Methylation 450K array. We corrected for demographics, cell composition, and multiple testing (Benjamini-Hochberg) and verified hits using bisulfite PCR pyrosequencing and qPCR. To extend these findings to a clinically relevant tissue, we investigated DNA methylation and gene expression of mucin 4 (MUC4), in nasal brushings from a separate validation cohort exposed to birch pollen. RESULTS: In PBMCs of allergic rhinitis participants, 42 sites showed significant DNA methylation changes of 2% or greater. DNA methylation changes in tryptase gamma 1 (TPSG1), schlafen 12 (SLFN12), and MUC4 in response to exposure were validated by pyrosequencing. SLFN12 DNA methylation significantly correlated with symptoms (P < 0.05), and baseline DNA methylation pattern was found to be predictive of symptom severity upon grass allergen exposure (P = 0.029). Changes in MUC4 DNA methylation in nasal brushings in the validation cohort correlated with drop in peak nasal inspiratory flow (Spearman's r = 0.314, P = 0.034), and MUC4 gene expression was significantly increased (P < 0.0001). CONCLUSION: This study revealed novel and rapid epigenetic changes upon exposure in a controlled allergen challenge facility, and identified baseline epigenetic status as a predictor of symptom severity.

[Undesired side effects of tapentadol in comparison to oxycodone. A meta-analysis of randomized controlled comparative studies]. / Unerwünschte Nebenwirkungen von Tapentadol im Vergleich zu Oxycodon. Eine Metaanalyse randomisierter, kontrollierter Vergleichsstudien.

OBJECTIVE: Tapentadol is a new centrally acting analgesic with a dual mode of action as an agonist of the µ-opioid receptor and as a norepinephrine reuptake inhibitor. The aim of the present study was to evaluate the results from randomized controlled trials investigating the relative amount of adverse effects using tapentadol or oxycodone for the treatment of pain. METHODS: A quantitative systematic review was carried out according to the PRISMA recommendations on randomized controlled trials comparing tapentadol and oxycodone in pain treatment. The incidences of typical adverse side effects of opioid-based analgesic therapy (e.g. nausea, vomiting, obstipation or pruritus) were extracted and the pooled relative risks (RR) with corresponding 95% confidence intervals (CI) were calculated. RESULTS: A total of 9 trials involving 7,948 patients were included and of these 2,810 patients were treated with oxycodone and 5,138 were treated with tapentadol in equivalent analgesic dosages as documented by an equivalent analgesic effect. The risk of typical opioid-based adverse effects, such as nausea (RR 0.61; 95% CI 0.57-0.66), vomiting (RR 0.50, 95% CI: 0.41-0.60), obstipation (RR 0.47, 95%-CI 0.40-0.56), dizziness (RR 0.86, 95% CI 0.78-0.95), somnolence (RR 0.76, 95% CI 0.67-0.86) and pruritus (RR 0.46, 95% CI 0.37-0.58) was reduced when tapentadol was used for analgesic treatment. These adverse effects were investigated in all nine trials. The risk for dryness of the mouth (6 trials, 6,218 patients, RR 1.79, 95% CI 1.40-2.29) and dyspepsia (1 trial, 646 patients, RR 2.75, 95% CI 1.09-6.94) was increased when tapentadol was used instead of oxycodone. There were no significant differences in the relative risk for any other investigated adverse effect such as dysentery, headache or fatigue. CONCLUSION: The results show that using tapentadol significantly reduces the risk of the typical opioid-based adverse effects compared with oxycodone while providing equivalent analgesic treatment.

[Implementation of new standards in anaesthesia. Exemplified by the ad hoc introduction of desflurane in 10 German hospitals]. / Implementierung neuer Standards in der Anästhesie. Beispiel der Ad-hoc-Einführung von Desfluran an 10 deutschen Krankenhäusern.

BACKGROUND: According to numerous pharmacoeconomic studies new anaesthesia techniques can improve recovery times and thus can have a positive economic impact on patient turnover. However, artificial study protocols do not always match real world situations and thus the practical impact of such studies remains unclear. MATERIAL AND METHODS: At 10 hospitals exclusively using sevoflurane as a volatile anaesthetic, the ad hoc implementation of desflurane was studied with respect to post-anaesthetic recovery times (primary endpoint) and postoperative outcome measured by the Quality of Recovery Score- (QoR-)40, on the first postoperative day was investigated. Randomization of patients undergoing elective surgical procedures under general anaesthesia with sevoflurane (n=186) or desflurane (n=176) was started immediately after a period of a few days after introducing the new drug to all participants. Except for the volatile anaesthetic the anaesthetic procedure was performed according to local standing operating procedures. RESULTS: All parameters indicating the immediate postanaesthetic recovery were superior in the patients receiving desflurane (mean±SD). Time to extubation was accelerated from 8.7±9.7 to 6.2±6.8 min. Times to recalling name and date of birth were accelerated by 2.6 and 3.8 min, respectively. Transferring the patients from the operating theatre to the post-anaesthetic recovery unit was 17.3±11.5 min after sevoflurane and 13.7±7.8 min after anaesthesia with desflurane. Eligibility for discharge according to a modified Aldrete score (White and Song 1999) was reached after 103±98 and 79±76 min, respectively. The postoperative recovery (QoR 40 questionnaire) did not differ 24 h later. DISCUSSION: The implementation of a new drug (here: desflurane to substitute sevoflurane) can improve speed of recovery immediately after termination of anaesthesia even after a very short period of introducing the new technique but has no positive long term effects. Thus, the results of this trial performed under a real world scenario (health service research) without tight standardization by an artificial study protocol supports the results originating from randomized controlled clinical trials.

[Prophylaxis of nausea and vomiting in the postoperative phase: relative effectiveness of droperidol and metoclopramide]. / Prophylaxe von Übelkeit und Erbrechen in der postoperativen Phase : Relative Effektivität von Droperidol und Metoclopramid.

OBJECTIVE: The aim of the present study was to conduct a meta-analysis of the results from randomized controlled trials investigating the relative efficacy of droperidol versus metoclopramide for the prevention of postoperative nausea and vomiting (PONV). METHODS: A systematic literature search for randomized controlled trials comparing droperidol and metoclopramide for the prevention of PONV was performed according to the PRISMA recommendations. The incidence of PONV within the early (0-6 h) and cumulative postoperative periods (0-48 h) was collated and the pooled relative risk (RR) with the corresponding 95% confidence interval (CI) was calculated. Results from a subgroup analysis are presented excluding the data of a Japanese group (Fujii et al.) which are given in parentheses. RESULTS: A total of 41 (30) trials with a total number of 3,491 (2,721) patients were included and of these 12 (8) trials with 1,403 (1,083) patients reported data of the early period and 32 (21) studies with 2,656 (1,836) patients comprised data of the cumulative period. A total of 1,797 (1,309) patients were treated with droperidol (0.25-5 mg) and 1,694 (1,412) with metoclopramide (5-50 mg). In the early period the risk for PONV after metoclopramide was 35% (95%-CI: 17-57%) higher than after prophylaxis with droperidol (without Fujii data: 46%; 23-73%). During the cumulative period the risk for PONV after metoclopramide was increased by 20% (95%-CI: 7-37%) compared to droperidol (without Fujii data: 25%; 4-50%). Due to heterogenous dosing of both drugs subgroup analyses with distinct dose intervals were performed with increments of 0.75 mg for droperidol and 7 mg for metoclopramide. Droperidol was superior in 17 (12) out of 19 (14) subgroup analyses. Comparing recommended doses of droperidol (0.75-1.5 mg) with low doses of metoclopramide (7-14 mg) and medium metoclopramide doses (14-21 mg) PONV was increased by 12% (95%-CI: -11% to 42%) and 32% (95%-CI: 4%-66%), respectively when metoclopramide instead of droperidol was used. When higher doses of metoclopramide (>20 mg) were used the superiority of droperidol was less pronounced and did not reach statistical significance due to the limited numbers of trials included in this analysis (3 studies, 662 patients). The risk for PONV after high-dose metoclopramide was increased by 13% (95%-CI: -21% to +61%) for the early period and by 19% (95%-CI: -11% to +57%) for the cumulative observation period. CONCLUSION: For the prevention of postoperative nausea and vomiting droperidol is significantly superior to metoclopramide doses below 20 mg. There was no obvious positive dose response with respect to increasing doses of metoclopramide. There was also a trend towards higher efficacy of droperidol compared to higher doses of metoclopramide (≥20 mg). However, there were not enough comparative studies to show a statistically significant result in this subgroup analysis. These data support the notion that droperidol in low doses may represent the more effective D(2)-antagonist for a pharmacological armamentarium to cope with PONV.

Prevention and control of postoperative nausea and vomiting in post-craniotomy patients.

Postoperative nausea and vomiting (PONV) are the most frequent side-effects in the postoperative period, impairing subjective well-being and having economic impact due to delayed discharge. However, emetic symptoms can also cause major medical complications, and post-craniotomy patients may be at an increased risk. A review and critical appraisal of the existing literature on PONV in post-craniotomy patients, and a comparison of these findings with the current knowledge on PONV in the general surgical population, leads to the following conclusions: (1) Despite the lack of a documented case of harm caused by retching or vomiting in a post-craniotomy patient, the potential risk caused by arterial hypertension and high intra-abdominal/intra-thoracic pressure leading to high intracranial pressure, forces to avoid PONV in these patients. (2) There is unclarity about a specifically increased (or decreased) risk for PONV in post-craniotomy patients compared with other surgical procedures. (3) The decision whether or not to administer an antiemetic should not be based primarily on risk scores for PONV but on the likelihood for potential catastrophic consequences of PONV. If such a risk cannot be ruled out, a multimodal antiemetic approach should be considered regardless of the individual risk. (4) Randomized controlled trials with antiemetics in post-craniotomy patients are limited with respect to sample size and methodological quality. This also impacts upon the meaning of meta-analyses performed with trials that showed marked heterogeneity and inconclusive results. (5) No studies on the treatment of established PONV are available. This highlights the need to transfer knowledge about PONV treatment from other surgical procedures. (6) Despite the possibility that PONV in post-craniotomy patients can be triggered by specific conditions (e.g. surgery near the area postrema at the floor of the fourth ventricle with the vomiting centre located nearby), recommendations based on trials in post-craniotomy patients may be flawed. Thus, general knowledge on prevention and treatment of PONV must adopted for craniotomy settings.

Risk factors for prilocaine-induced methaemoglobinaemia following peripheral regional anaesthesia.

BACKGROUND: The local anaesthetic prilocaine has a low systemic toxicity mainly because of a high absorption in the lung and a large volume of distribution and thus is associated with a lower risk of neurological or cardiac side-effects. However, the major disadvantage is the formation of methaemoglobin by its metabolite o-toluidine. This prospective observational study was performed to identify factors that are associated with increased prilocaine-induced methaemoglobinaemia. PATIENTS AND METHODS: One Hundred and sixty two patients undergoing major knee surgery under general anaesthesia combined with peripheral nerve blocks (femoral nerve block, combined femoral/sciatic nerve block or lumbar plexus block) received a single bolus injection of 300 or 400 mg prilocaine about 30 min before surgery via a catheter. The proper placement was verified using nerve stimulation via a stimulating catheter. Three hours after prilocaine injection, venous blood samples were drawn and methaemoglobin levels were measured by standard photometric technique. Data was subjected to a stepwise multiple regression analysis. RESULTS: The mean methaemoglobin for all patients was 2.7% (range: 0.9-15.4%). A higher dose of prilocaine and younger age were the most important predictive factors for higher methaemoglobin formation. Female sex and to a lesser extent the use of high-concentration/low-volume prilocaine also increased methaemoglobin levels. These four factors of the model explain 36% of the total variance. Other investigated factors, including the patient's height, weight, body mass index, the site of catheter insertion, the anaesthetist's judgement concerning the difficulty of catheter placement, duration of catheter placement or an inadvertent puncture of a venous or arterial vessel, had no significant impact on the concentration of methaemoglobin. CONCLUSION: The use of prilocaine for regional block is safe, since the older patients who might be more susceptible to suffer from clinical symptoms of methaemoglobinaemia usually form less methaemoglobin. However, since prediction of high methaemoglobin levels is difficult, anaesthesiologists performing regional blocks in patients who might be jeopardized by a decreased oxygen transport capacity should avoid high doses of prilocaine.

[Is a blockade of the lateral cutaneous nerve of the thigh an alternative to the classical femoral nerve blockade for knee joint arthroscopy? A randomised controlled study]. / Ist die Blockade des N. cutaneus femoris lateralis eine Alternative zu einer klassischen Femoralisblockade bei Kniegelenkarthroskopien? Eine randomisierte, kontrollierte Untersuchung.

BACKGROUND: Gaps in the distribution area of the lateral femoral cutaneous nerve (LFCN) are assumed to be the reason for pain caused by a thigh tourniquet when performing a femoral nerve (FN) block according to Winnie. The aim of the study was to evaluate if a direct single blockade of the LFCN in patients undergoing knee surgery resulted in a better tolerance to the tourniquet with equally good analgesic quality during surgery. METHODS: A total of 40 patients undergoing knee arthroscopy received a proximal blockade of the sciatic nerve and randomly either an FN or an LFCN block. Practicability, onset time, quality of sensory and motor block, and clinical effectiveness during tourniquet and surgery were assessed. RESULTS: Stimulation time was significantly longer in the LFCN than in the FN group. Quality of sensory and motor block was worse in the LFCN than the NF group. Of the LFCN patients 65% indicated troublesome paraesthesia or pain when a tourniquet was placed, compared to 35% of the FN patients. Of the LFCN patients 50% had pain during cutaneous incision, compared to none of the FN group. During the course of surgery, 70% of the LFCN patients needed supplemental systemic analgesia, but this was required by only 30% of the FN group. CONCLUSION: An LFCN block is not a suitable alternative to an FN block for regional anaesthesia. For patients with contraindications for an FN block according to Winnie (e.g. vessel surgery in the groin) other more effective methods are available.

The development and validation of a risk score to predict the probability of postoperative vomiting in pediatric patients.

Risk scores to predict the occurrence of postoperative vomiting (PV) or nausea and vomiting that were developed for adult patients do not fit for children, because several risk factors are difficult to assess or are usually not applicable in pediatric patients (e.g., smoking status). Thus, in the present study, we sought to develop and to validate a simple score to predict PV in children (POVOC-score). Development and validation of the new score was based on data from 4 independent institutions of 1257 children (aged 0-14 yr) undergoing various types of surgery under general anesthesia without antiemetic prophylaxis. Preoperatively, several potential risk factors were recorded. Postoperatively, the occurrence of PV was observed for up to 24 h. The dataset was randomly split into an evaluation set (n = 657) that was analyzed using a forward logistic regression technique and a validation set (n = 600) that was used to confirm the accuracy of prediction by means of the area under a receiver operating characteristic curve. Four independent risk factors for PV were identified in the final analysis: duration of surgery >/=30 min, age >/=3 yr, strabismus surgery, and a positive history of PV in the children or PV/postoperative nausea and vomiting in relatives (mother, father, or siblings). The incidence of PV was 9%, 10%, 30%, 55%, and 70% for 0, 1, 2, 3, and 4 risk factors observed. Using these incidences as cut-off values in the validation dataset, the area under the receiver operating characteristic curve was 0.72 (95% confidence interval: 0.68-0.77). Our data suggest that PV can be predicted with an acceptable accuracy using a four-item simplified risk score.

[Does fentanyl or midazolam improve patient's comfort and cooperation when given for regional catheter placement? A randomized, controlled and double-blind trial]. / Verbessern intravenöses Fentanyl oder Midazolam vor Durchführung einer peripheren Regionalanästhesie Patientenakzeptanz und Kooperativität bei der Katheteranlage? Eine randomisierte, placebokontrollierte und doppelblinde Untersuchung.

BACKGROUND: The procedure of placing a catheter for continuous regional anaesthesia is often associated with fear and pain in the patient. Thus, we evaluated the use of midazolam and fentanyl to improve patient's comfort and cooperation. METHODS: After an oral dose of 20 mg clorazepate, 174 patients receiving peripheral nerve catheters for regional anaesthesia where randomized into 3 groups to receive either intravenous placebo, 3 mg midazolam or 0.1 mg fentanyl immediately before catheter placement in a double-blind manner. Stepwise regression analysis was used to identify factors associated with patient's assessment of subjective discomfort (measured using a VAS 0-10) during the procedure. Amnesia was evaluated 24 h later. The anaesthetist rated patient's cooperation during catheter placement. RESULTS: Female sex and longer duration of catheter placement had significant negative impact on patient's comfort, whereas fentanyl showed an improvement. Age, body mass index, midazolam and the type of catheter had no influence. The following day 27% of the midazolam group, 6% of the placebo group and 9% of the fentanyl patients did not remember catheter placement. Patient's cooperation was poor in 26% of the midazolam patients but only in 9% of the placebo and 3% of the patients receiving fentanyl. Of the placebo patients 18.4% had to be supplemented with fentanyl because they found the procedure of catheter placement unbearable. No side effects occurred in either group. CONCLUSION: As patient's comfort and cooperation were significantly improved by fentanyl, we recommend fentanyl to facilitate catheter placement for regional anaesthesia.

Applicability of risk scores for postoperative nausea and vomiting in adults to paediatric patients.

BACKGROUND: Scores to predict the occurrence of postoperative vomiting (PV) or nausea and vomiting (PONV) are well established in adult patients. The aim of this survey was to evaluate the applicability of risk scores developed and tested in adult patients in 983 paediatric patients (0-12 yr) undergoing various surgical procedures. METHOD: The predictive properties of five models were compared with respect to discriminating power (measured by the area under a receiver operating characteristic curve) and calibration (comparison of the predicted and the actual incidences of the disease by weighed linear regression analysis). RESULTS: The cumulative incidence of PV was 33.2% within 24 h. The discriminating power was low and insufficient in all models tested (0.56-0.65). Furthermore, the predicted incidences of the scores correlated only vaguely with the actual incidences observed. CONCLUSION: Specialized scores for children are required. These might use the history of PV, strabismus surgery, duration of anaesthesia > or =45 min, age > or =5 yr and administration of postoperative opioids as independent risk factors.

[Is ginger a relevant antiemetic for postoperative nausea and vomiting?]. / Ist Ingwer ein sinnvolles Antiemetikum für die postoperative Phase? Eine Metaanalyse randomisierter kontrollierter Studien.-

OBJECTIVE: Ginger (Zingiber officinale) has traditionally been used in China for gastrointestinal symptoms, including nausea and vomiting. A recent systematic review on the possible antiemetic effect of ginger for various indications, including PONV, morning sickness, and motion sickness, concluded that ginger was a promising antiemetic herbal remedy, but the clinical data were insufficient to draw firm conclusions. Since that publication, additional data has accumulated and thus an updated meta-analysis was performed. METHODS: A systematic search of the literature was performed using different search strategies in MEDLINE, EMBASE, and the Cochrane Library. Six randomized controlled trials including 538 patients were identified investigating ginger to prevent postoperative nausea and vomiting (PONV). Data on the incidences of PONV, nausea, vomiting, and the need for rescue antiemetics within the first 24 postoperative hours were extracted and the pooled relative risk and the numbers needed to treat (NNT) were calculated using a random effects model. RESULTS: The pooled relative risk to suffer from PONV after pre-treatment with ginger was 0.84 (95 %-confidence interval 0.69 - 1.03). About 11 patients must be treated with ginger for one additional patient remaining free from PONV (NNT: 11; 95 %-CI: 6 - 250). Results for nausea, vomiting, and need for antiemetic rescue treatment are similar. CONCLUSION: Ginger is not a clinically relevant antiemetic in the PONV setting.

[Prediction of postoperative nausea and vomiting using an artificial neural network]. / Vorhersage von Ubelkeit und Erbrechen in der postoperativen Phase durch ein künstliches neuronales Netz.

OBJECTIVE: Postoperative nausea and vomiting (PONV) are still frequent side-effects after general anaesthesia. These unpleasant symptoms for the patients can be sufficiently reduced using a multimodal antiemetic approach. However, these efforts should be restricted to risk patients for PONV. Thus, predictive models are required to identify these patients before surgery. So far all risk scores to predict PONV are based on results of logistic regression analysis. Artificial neural networks (ANN) can also be used for prediction since they can take into account complex and non-linear relationships between predictive variables and the dependent item. This study presents the development of an ANN to predict PONV and compares its performance with two established simplified risk scores (Apfel's and Koivuranta's scores). METHODS: The development of the ANN was based on data from 1,764 patients undergoing elective surgical procedures under balanced anaesthesia. The ANN was trained with 1,364 datasets and a further 400 were used for supervising the learning process. One of the 49 ANNs showing the best predictive performance was compared with the established risk scores with respect to practicability, discrimination (by means of the area under a receiver operating characteristics curve) and calibration properties (by means of a weighted linear regression between the predicted and the actual incidences of PONV). RESULTS: The ANN tested showed a statistically significant ( p<0.0001) and clinically relevant higher discriminating power (0.74; 95% confidence interval: 0.70-0.78) than the Apfel score (0.66; 95% CI: 0.61-0.71) or Koivuranta's score (0.69; 95% CI: 0.65-0.74). Furthermore, the agreement between the actual incidences of PONV and those predicted by the ANN was also better and near to an ideal fit, represented by the equation y=1.0x+0. The equations for the calibration curves were: KNN y=1.11x+0, Apfel y=0.71x+1, Koivuranta 0.86x-5. CONCLUSION: The improved predictive accuracy achieved by the ANN is clinically relevant. However, the disadvantages of this system prevail because a computer is required for risk calculation. Thus, we still recommend the use of one of the simplified risk scores for clinical practice.

Treatment of hiccup during general anaesthesia or sedation: a qualitative systematic review.

BACKGROUND AND OBJECTIVE: Acute hiccup is a minor complication that can occur during sedation or general anaesthesia. The disorder can disturb the surgical field, might interfere with lung ventilation or could hamper diagnostic procedures. The objective was to perform a systematic search for interventions aimed at treating hiccup occurring during anaesthesia or sedation. METHODS: A systematic search for reports describing interventions to treat hiccup in conjunction with anaesthesia was carried out (MEDLINE, EMBASE, Cochrane-Library, manual screening of reference lists and review articles, up to December 2001). Search terms were 'hiccup', 'singultus' or 'hiccough'. RESULTS: Twenty-six reports involving approximately 581 patients focused on hiccup remedies in the anaesthesia setting. Only one report was substantiated by a randomized controlled trial. This investigated methylphenidate 10 mg intravenously in 51 patients, which did not show a beneficial effect compared with placebo. Hiccup was a self-limiting phenomenon. Case series and case reports focused on various systemically applied drugs in 12 reports, stimulating techniques (e.g. pharyngeal stimulation) in seven, topical applied remedies (e.g. intranasal ice-cold water) in four, and ventilation techniques (e.g. continuous positive pressure ventilation) in two. CONCLUSIONS: A large variety of interventions have been proposed for the treatment of hiccup during anaesthesia and sedation. However, perioperative treatment is still based on empirical findings and no treatment is 'evidence-based'. Thus, no valid recommendations for the treatment of hiccup can be derived. Uncontrolled observations are inadequate to establish treatment efficacy.

[Artificial neural networks. Theory and applications in anesthesia, intensive care and emergency medicine]. / Künstliche neuronale Netze. Theorie und Anwendungen in der Anästhesie, Intensiv- und Notfallmedizin.

Artificial neural networks (ANN) are constructed to simulate processes of the central nervous system of higher creatures. An ANN consists of a set of processing units (nodes) which simulate neurons and are interconnected via a set of "weights" (analogous to synaptic connections in the nervous system) in a way which allows signals to travel through the network in parallel. The nodes (neurons) are simple computing elements. They accumulate input from other neurons by means of a weighted sum. If a certain threshold is reached the neuron sends information to all other connected neurons otherwise it remains quiescent. One major difference compared with traditional statistical or rule-based systems is the learning aptitude of an ANN. At the very beginning of a training process an ANN contains no explicit information. Then a large number of cases with a known outcome are presented to the system and the weights of the inter-neuronal connections are changed by a training algorithm designed to minimise the total error of the system. A trained network has extracted rules that are represented by the matrix of the weights between the neurons. This feature is called generalisation and allows the ANN to predict cases that have never been presented to the system before. Artificial neural networks have shown to be useful predicting various events. Especially complex, non-linear, and time depending relationships can be modelled and forecasted. Furthermore an ANN can be used when the influencing variables on a certain event are not exactly known as it is the case in financial or weather forecasts. This article aims to give a short overview on the function of ANN and their previous use and possible future applications in anaesthesia, intensive care, and emergency medicine.

Patient preferences for immediate postoperative recovery.

BACKGROUND: Several attempts have been made to evaluate patients' concerns with respect to postoperative recovery. To identify aspects of postoperative recovery relevant to patients, several methodological and statistical approaches have been used. One of the first to provide useful information was Fredrick Orkin who used conjoint analysis. This methodology is usually performed by market researchers to learn about the relative importance of product attributes. We used conjoint analysis in the present study. METHODS: A total of 220 patients undergoing preoperative anaesthetic examination before impending surgery under general anaesthesia were asked to rate nine scenarios during immediate postoperative recovery based on four factors (alertness, pain, postoperative nausea and vomiting (PONV), and extra costs) each with three levels. Using conjoint analysis the relative impact of each factor on ranking the scenarios was assessed. RESULTS: The relative importance of the four factors (as a percentage of the preference decision) was PONV (49%), pain (27%), alertness (13%), and additional costs (11%). CONCLUSION: Avoidance of PONV is a major concern for patients before surgery.

Impact of a multimodal anti-emetic prophylaxis on patient satisfaction in high-risk patients for postoperative nausea and vomiting.

Postoperative nausea and vomiting (PONV) are frequent and unpleasant symptoms. This prospective study aimed to assess the efficacy of a multimodal approach to prevent PONV, and patient satisfaction using the willingness-to-pay method. Two validated risk scores were applied to forecast the individual risk for PONV in 900 consecutive patients of whom 108 were identified as high-risk patients (predicted risk: 79-87%). High-risk patients received multimodal anti-emetic prophylaxis: total intravenous anaesthesia with propofol, high fractional inspired oxygen (80%), omission of nitrous oxide, dexamethasone 8 mg, haloperidol 10 microg.kg(-1), and tropisetron 2 mg. Of the remaining patients with low or moderate risk for PONV, a random sample of 71 females received balanced propofol-desflurane anaesthesia without prophylactic anti-emetics. All patients were interviewed 2 and 24 h after surgery for occurrence of nausea and vomiting. Patient satisfaction was measured using the willingness-to-pay method. The incidence of PONV (95%-confidence interval) in the control-group was 41% (29-51%), slightly lower than predicted by the risk scores (53-57%). The multimodal anti-emetic approach reduced the predicted risk (79-87%) in the high risk-group to 7% (3-14%). This was associated with a high willingness-to-pay median (25th/75th percentile) of 84 UK pounds (33-184 UK pounds) in the multimodal anti-emetic group compared to 14 UK pounds (4-30 UK pounds) in the control group. A multimodal anti-emetic approach can considerably reduce the incidence of PONV in high-risk patients and is associated with a high patient satisfaction as measured by the willingness-to-pay method.

[Transient neurologic symptoms after spinal anesthesia. A quantitative systematic overview (meta-analysis) of randomized controlled studies]. / Transiente neurologische Symptome nach Spinalanästhesie. Eine quantitative systematische Ubersicht (Metaanalyse) randomisierter kontrollierter Studien.

BACKGROUND: Transient neurologic symptoms (TNS) after spinal anesthesia (SPA) is defined as back pain with radiation or dysesthesia in the buttocks, thighs, hips and calves, occurring within 24 h after recovery from otherwise uneventful SPA. The symptoms last for about 1-3 days but neurophysiologic evaluation does not show pathologic findings. The type and the preparation of the local anesthetic drug (baricity, concentration, additives or preservatives) are most often discussed as the underlying cause of TNS. METHODS: Randomized controlled comparative studies reporting the incidence of TNS were systematically searched. Descriptive statistics are presented summarizing the identified trials and the pooled relative risk (RR), the number-needed-to-harm (NNH) with their 95% confidence intervals (95%-CI) were calculated using a random effects model. RESULTS: A total of 29 studies with a 2,813 patients fulfilled the inclusion criteria. Summarizing all patients in these trials without further adjustment, the incidence of TNS was 16.9% after lidocaine, 19.1% after mepivacaine, but only 1.1% after bupivacaine and 1.7% after prilocaine. For tetracaine, procaine, and ropivacaine there were too few studies to draw meaningful conclusions. Using meta-analysis techniques these data were confirmed: the pooled relative risk (RR) for suffering from TNS was 6.7-fold higher after lidocaine (95%-CI: 2.5-18) than after SPA with bupivacaine and 5.5-fold higher (95%-CI: 2-15) than after prilocaine. Furthermore, data show that baricity, concentration of the local anesthetic, and addition of vasoconstrictors have no significant influence on the occurrence of TNS. CONCLUSION: Prilocaine and bupivacaine for SPA are associated with less TNS than lidocaine and mepivacaine. For the other local anesthetics there were not enough comparative trials to give conclusive recommendations.

Dimenhydrinate for prophylaxis of postoperative nausea and vomiting: a meta-analysis of randomized controlled trials.

BACKGROUND: Diphenhydramine and its theoclate salt dimenhydrinate are traditional antiemetics still in use. However, so far the quantitative effect of dimenhydrinate in the prophylaxis of postoperative nausea and vomiting (PONV) has not been evaluated systematically. METHODS: Results from randomized controlled trials investigating the efficacy of dimenhydrinate vs. a control to prevent PONV were included in a meta-analysis. Studies were systematically searched through MEDLINE, EMBASE, the Cochrane-Library, manually screening of reference lists of matching review articles and current issues of locally available peer-reviewed anesthesia journals, up to June 2001. The numbers of patients with complete absence of PONV within 6 h and within 48 h after surgery were extracted as the main end point. Pooled relative benefits (RB) and numbers-needed-to-treat (NNT) with their corresponding 95% confidence intervals (CI) were calculated using a random effects model. This quantitative systematic review was performed following the recommendations of the QUORUM statement. In all, 18 trials with 3045 patients were included in the analysis: 1658 patients received a placebo (control) and 1387 patients received dimenhydrinate. RESULTS: The RB to stay completely free of PONV was 1.2 (95% CI: 1.1-1.4) for the early period (NNT = 8; 95% CI: 5-25) and 1.5 (1.3-1.8) for the overall investigated period (NNT = 5; 95% CI: 3-9). CONCLUSION: Dimenhydrinate is a traditional and inexpensive antiemetic with an efficacy that might be considered as clinically relevant. Although in use for a long time, the dose-response, precise estimation of side-effects, optimal time of administration and the benefit of repetitive doses still remain unclear.

[Droperidol and dimenhydrinate alone or in combination for prevention of postoperative nausea and vomiting]. / Droperidol und Dimenhydrinat alleine und in Kombination zur Prophylaxe von Ubelkeit und Erbrechen in der postoperativen Phase.

BACKGROUND: Droperidol and dimenhydrinate are inexpensive antiemetic drugs. Droperidol, especially, has been studied extensively in the past, but there are no studies that used the combination of both drugs for prevention of postoperative nausea and vomiting (PONV). Thus, the aim of this randomised controlled and double-blinded study was to evaluate the antiemetic efficacy and the side effects of such a combination therapy. METHODS: 240 inpatients undergoing ENT surgery under general anaesthesia were randomised to receive one of four antiemetic regimes: placebo, dimenhydrinate (1 mg x kg-1), droperidol (15 micrograms x kg-1), or the combination of both drugs (droperidol 15 micrograms x kg-1 + dimenhydrinate 1 mg x kg-1) was administered after induction of anaesthesia and repeated 6 hours after the first administration. For general anaesthesia a standardised technique including benzodiazepine premedication, propofol, desflurane in N2O/O2, vecuronium, and a continuous infusion of remifentanil was used. Postoperative analgesia and antiemetic rescue medication were standardised. Episodes of vomiting, retching, nausea, and the need for additional antiemetics were recorded for 24 hours. The main goal of the study was to increase the number of patients who were completely free from PONV (chi 2-test with Fisher-Yates' correction). Furthermore, the severity of PONV was analysed using a standardised scoring algorithm. RESULTS: Data of 227 patients could be analysed. The incidence of patients who suffered from PONV was 41.3% (95%-confidence interval: 29-55%) in the placebo-group. Dimenhydrinate alone reduced PONV to 34.5% (95%-CI: 22-48%). This marginal effect and the effect of droperidol (PONV: 26.4% (95%-CI: 15-40%)) could not be proven statistically, since the power of the study was too small. The combination of both drugs decreased PONV to 19.6% (95%-CI: 10-32%) and also reduced the severity of the symptoms to a clinically acceptable level. CONCLUSION: Dimenhydrinate failed to reduce the incidence and severity of PONV. The efficiency of droperidol given alone was within the ranges previously known from metaanalytic data. The combination of both drugs showed a moderate synergistic effect.