Population kinetic/pharmacodynamic modelling of the haemodynamic effects of cafedrine/theodrenaline (Akrinor) under general anaesthesia.

AIMS: The 20:1 combination of cafedrine and theodrenaline (C/T) is widely used in Germany for the treatment of arterial hypotension. Since there is little knowledge about the impact of covariates on the effect, the aim was to develop a kinetic/pharmacodynamic covariate model describing mean arterial pressure (MAP), systolic (SBP) and diastolic blood pressure (DBP), and heart rate (HR) for 30 min after the administration of C/T. METHODS: Data of patients receiving C/T from the HYPOTENS study (NCT02893241, DRKS00010740) were analysed using nonlinear mixed-effects modelling techniques. RESULTS: Overall, 16 579 measurements from 315 patients were analysed. The combination of two kinetic compartments and a delayed effect model, coupled with distinct Emax models for HR, SBP and DBP, described the data best. The model included age, sex, body mass index (BMI), antihypertensive medication, American Society of Anaesthesiologists (ASA) physical status classification grade, baseline SBP at the time of hypotension and pre-surgery HR as covariates (all P < .001). A higher baseline SBP led to a lower absolute increase in MAP. Patients with higher age, higher BMI and lower ASA grade showed smaller increases in MAP. The initial increase was similar for male and female patients. The long-term effect was higher in women. Concomitant antihypertensive medication caused a delayed effect and a lower maximum MAP. The HR increased only slightly (median increase 2.6 bpm, P < .001). CONCLUSIONS: Seven covariates with an impact on the effect of C/T could be identified. The results will enable physicians to optimize the dose with respect to individual patients.

Treatment of spinal anaesthesia-induced hypotension with cafedrine/theodrenaline versus ephedrine during caesarean section: Results from HYPOTENS, a national, multicentre, prospective, noninterventional study.

BACKGROUND: In Germany, hypotension induced by spinal anaesthesia is commonly treated with a combination of cafedrine hydrochloride (C, 200 mg) and theodrenaline hydrochloride (T, 10 mg) in 2 ml. We compared the effectiveness of C/T with ephedrine. OBJECTIVES: The primary objectives were to assess the speed of onset and the ability to restore blood pressure without an increase in heart rate. Secondary objectives were to evaluate maternal/foetal outcomes and the number of required additional boluses or other additional measures. DESIGN: HYPOTENS was a national, multicentre, prospective, open-label, two-armed, noninterventional study comparing C/T with ephedrine in two prospectively defined cohorts. This study relates to the cohort of patients receiving spinal anaesthesia for caesarean section. SETTING: German hospitals using either C/T or ephedrine in their routine clinical practice. PATIENTS: Women aged at least 18 years receiving spinal anaesthesia for caesarean section. INTERVENTIONS: Bolus administration of C/T or ephedrine at the discretion of the attending anaesthesiologist. MAIN OUTCOME MEASURES: Endpoints within 15 min after initial administration of C/T or ephedrine were area under the curve between the observed SBP and the minimum target SBP; and incidence of newly occurring heart rate of at least 100 beats min-1. RESULTS: Although effective blood pressure stabilisation was achieved with both treatments, this effect was faster and more pronounced with C/T (P < 0.0001). The incidence of tachycardia and changes in heart rate were higher with ephedrine (P < 0.01). Fewer additional boluses (P < 0.01) were required with C/T. Although favourable neonatal outcomes were reported in both groups, base deficit and lactate values were greater with ephedrine (P < 0.01). Physician satisfaction was higher with C/T. CONCLUSIONS: After C/T, tachycardia was not a problem, providing an advantage over ephedrine. Fewer additional boluses were required with C/T, suggesting greater effectiveness. An increased base deficit with ephedrine suggests reduced oxygen supply or increased demands in foetal circulation. TRIALS REGISTRATION: Clinicaltrials.gov: NCT02893241, German Clinical Trials Register: DRKS00010740.

Context-sensitive decrement times for inhaled anesthetics in obese patients explored with Gas Man®.

Anesthesia care providers and anesthesia decision support tools use mathematical pharmacokinetic models to control delivery and especially removal of anesthetics from the patient's body. However, these models are not able to reflect alterations in pharmacokinetics of volatile anesthetics caused by obesity. The primary aim of this study was to refine those models for obese patients. To investigate the effects of obesity on the elimination of desflurane, isoflurane and sevoflurane for various anesthesia durations, the Gas Man® computer simulation software was used. Four different models simulating patients with weights of 70 kg, 100 kg, 125 kg and 150 kg were constructed by increasing fat weight to the standard 70 kg model. For each modelled patient condition, the vaporizer was set to reach quickly and then maintain an alveolar concentration of 1.0 minimum alveolar concentration (MAC). Subsequently, the circuit was switched to an open (non-rebreathing) circuit model, the inspiratory anesthetic concentration was set to 0 and the time to the anesthetic decrements by 67% (awakening times), 90% (recovery times) and 95% (resolution times) in the vessel-rich tissue compartment including highly perfused tissue of the central nervous system were determined. Awakening times did not differ greatly between the simulation models. After volatile anesthesia with sevoflurane and isoflurane, awakening times were lower in the more obese simulation models. With increasing obesity, recovery and resolution times were higher. The additional adipose tissue in obese simulation models did not prolong awakening times and thus may act more like a sink for volatile anesthetics. The results of these simulations should be validated by comparing the elimination of volatile anesthetics in obese patients with data from our simulation models.

[Patient-controlled Analgesia (PCA): an Overview About Methods, Handling and New Modalities]. / Patientenkontrollierte Analgesie: Methoden, Handhabung und Ausbaufähigkeit.

Patient-controlled analgesia (PCA) is one of the well established methods for the treatment of postoperative pain. A cochrane-review concluded that PCA is associated with better postoperative pain ratings and improved patient-satifaction compared to traditional way of administering opioids. Some prerequisites concerning patient selection, education of the patient and the medical staff, and supervision during PCA therapy are mandatory for a safe use of PCA. Current PCA modalities (intravenous and epidural routes of application) are expanded by newer, less invasive routes of drug administration, e.g. by the iontophoretic transdermal and the sublingual route. Their role in improving safety and the quality of pain therapy on the one hand side, and costs on the other hand side are discussion.

Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery.

BACKGROUND: The management of postoperative pain and recovery is still unsatisfactory in clinical practice. Opioids used for postoperative analgesia are frequently associated with adverse effects including nausea and constipation. These adverse effects prevent smooth postoperative recovery. On the other hand not all patients may be suited to, and take benefit from, epidural analgesia used to enhance postoperative recovery. The non-opioid lidocaine was investigated in several studies for its use in multi-modal management strategies to reduce postoperative pain and enhance recovery. OBJECTIVES: The aim of this review was to assess the effects (benefits and risks) of perioperative intravenous lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5 2014), MEDLINE (January 1966 to May 2014), EMBASE (1980 to May 2014), CINAHL (1982 to May 2014), and reference lists of articles. We searched the trial registry database ClinicalTrials.gov, contacted researchers in the field, and handsearched journals and congress proceedings. We did not apply any language restrictions. SELECTION CRITERIA: We included randomized controlled trials comparing the effect of continuous perioperative intravenous lidocaine infusion either with placebo, or no treatment, or with epidural analgesia in adults undergoing elective or urgent surgery under general anaesthesia. The intravenous lidocaine infusion must have been started intraoperatively prior to incision and continued at least until the end of surgery. DATA COLLECTION AND ANALYSIS: Trial quality was independently assessed by two authors according to the methodological procedures specified by the Cochrane Collaboration. Data were extracted by two independent authors. We collected trial data on postoperative pain, recovery of gastrointestinal function, length of hospital stay, postoperative nausea and vomiting (PONV), opioid consumption, patient satisfaction, surgical complication rates, and adverse effects of the intervention. MAIN RESULTS: We included 45 trials involving 2802 participants. Two trials compared intravenous lidocaine versus epidural analgesia. In all the remaining trials placebo or no treatment was used as a comparator. Trials involved participants undergoing open abdominal (12), laparoscopic abdominal (13), or various other surgical procedures (20).The risk of bias was low with respect to selection bias (random sequence generation), performance bias, attrition bias, and detection bias in more than 50% of the included studies. For allocation concealment and selective reporting the quality assessment yielded low risk of bias for only approximately 20% of the included studies.We found evidence of effect for intravenous lidocaine on the reduction of postoperative pain (visual analogue scale, 0 to 10 cm) compared to placebo or no treatment at 'early time points (one to four hours)' (mean difference (MD) -0.84 cm, 95% confidence interval (CI) -1.10 to -0.59; low-quality evidence) and at 'intermediate time points (24 hours)' (MD -0.34 cm, 95% CI -0.57 to -0.11; low-quality evidence) after surgery. However, no evidence of effect was found for lidocaine to reduce pain at 'late time points (48 hours)' (MD -0.22 cm, 95% CI -0.47 to 0.03; low-quality evidence). Pain reduction was most obvious at 'early time points' in participants undergoing laparoscopic abdominal surgery (MD -1.14, 95% CI -1.51 to -0.78; low-quality evidence) and open abdominal surgery (MD -0.72, 95% CI -0.96 to -0.47; moderate-quality evidence). No evidence of effect was found for lidocaine to reduce pain in participants undergoing all other surgeries (MD -0.30, 95% CI -0.89 to 0.28; low-quality evidence). Quality of evidence is limited due to inconsistency and indirectness (small trial sizes).Evidence of effect was found for lidocaine on gastrointestinal recovery regarding the reduction of the time to first flatus (MD -5.49 hours, 95% CI -7.97 to -3.00; low-quality evidence), time to first bowel movement (MD -6.12 hours, 95% CI -7.36 to -4.89; low-quality evidence), and the risk of paralytic ileus (risk ratio (RR) 0.38, 95% CI 0.15 to 0.99; low-quality evidence). However, no evidence of effect was found for lidocaine on shortening the time to first defaecation (MD -9.52 hours, 95% CI -23.24 to 4.19; very low-quality evidence).Furthermore, we found evidence of positive effects for lidocaine administration on secondary outcomes such as reduction of length of hospital stay, postoperative nausea, intraoperative and postoperative opioid requirements. There was limited data on the effect of IV lidocaine on adverse effects (e.g. death, arrhythmias, other heart rate disorders or signs of lidocaine toxicity) compared to placebo treatment as only a limited number of studies systematically analysed the occurrence of adverse effects of the lidocaine intervention.The comparison of intravenous lidocaine versus epidural analgesia revealed no evidence of effect for lidocaine on relevant outcomes. However, the results have to be considered with caution due to imprecision of the effect estimates. AUTHORS' CONCLUSIONS: There is low to moderate evidence that this intervention, when compared to placebo, has an impact on pain scores, especially in the early postoperative phase, and on postoperative nausea. There is limited evidence that this has further impact on other relevant clinical outcomes, such as gastrointestinal recovery, length of hospital stay, and opioid requirements. So far there is a scarcity of studies that have systematically assessed the incidence of adverse effects; the optimal dose; timing (including the duration of the administration); and the effects when compared with epidural anaesthesia.

Impact of medical training and clinical experience on the assessment of oxygenation and hypoxaemia after general anaesthesia: an observational study.

In Germany it is common practice to use pulse oximetry and supplementary oxygen only on request in patients breathing spontaneously transferred to the post-anaesthesia care unit (PACU) following surgery under general anaesthesia. The main aim was to study the influence of medical training and clinical experience on assessing SpO(2) and detecting hypoxaemia in these patients. The second aim was to do a preliminary assessment whether this practice can be found in countries other than Germany. Anaesthetists, nurses and medical students estimated SpO(2) in patients breathing room air at the end of transfer to the PACU following surgery (including all major surgical fields) under general anaesthesia. Estimated SpO(2) was compared to SpO(2) measured by pulse oximetry. A survey was carried out among European anaesthesists concerning the use of pulse oximetry and supplementary oxygen during patient transfer to the PACU. Hypoxaemia (SpO(2) < 90 %) occurred in 154 (13.5 %) out of 1,138 patients. Anaesthetists, nurses, and medical students identified only 25, 23, and 21 patients of those as being hypoxaemic, respectively. Clinical experience did not improve detection of hypoxaemia both in anaesthetists (p = 0.63) and nurses (p = 0.18). Use of pulse oximetry and supplemental oxygen during patient transfer to the PACU in European countries differs to a large extent. It seems to be applied only on request in many hospitals. Considering the uncertainty about deleterious effects of transient, short lasting hypoxaemia routine use of pulse oximetry is advocated for patient transfer to the PACU.

Feasibility and precision of subcutaneous continuous glucose monitoring in patients undergoing CABG surgery.

OBJECTIVES: To evaluate if subcutaneous continuous glucose monitoring (sCGM) is feasible in cardiac surgery and if reliable glucose values are reported under hypothermic extracorporeal circulation. DESIGN: Feasibility trial. SETTING: University hospital. PARTICIPANTS: Ten consecutive patients undergoing coronary artery bypass grafting. INTERVENTIONS: Prior to surgery, during hypothermic extracorporeal bypass, and 48 hours postoperatively, arterial blood glucose samples were compared with sCGM every 30 minutes. Statistical analysis utilized Clarke's error grid and Bland-Altman plot. MEASUREMENTS AND MAIN RESULTS: Three hundred fifty-one pairs of glucose measurements were recorded including 59 during hypothermic extracorporeal circulation. Agreement between these measurements was acceptable, with a regression line slope of 0.88 and an offset of 17.4 (p = 0.87). Error grid analysis indicated a safe margin of 99.1% within zone A (no clinical action needed) or zone B (values would not lead to inappropriate treatment). Only 0.9% were plotted in zone D (potentially dangerous failure). Measurements during hypothermic extracorporeal circulation were comparable. Correlation coefficient was 0.760. The offset regression line was more pronounced (50.9) with a flatter slope (0.640). Within the error grid all plot values were in zone A or B. CONCLUSIONS: sCGM compared with arterial blood gas glucose monitoring under hypothermic extracorporeal circulation appears to be feasible and reliable.

Quantifying prognosis with risk predictions.

Prognosis is a forecast, based on present observations in a patient, of their probable outcome from disease, surgery and so on. Research methods for the development of risk probabilities may not be familiar to some anaesthesiologists. We briefly describe methods for identifying risk factors and risk scores. A probability prediction rule assigns a risk probability to a patient for the occurrence of a specific event. Probability reflects the continuum between absolute certainty (Pi = 1) and certified impossibility (Pi = 0). Biomarkers and clinical covariates that modify risk are known as risk factors. The Pi as modified by risk factors can be estimated by identifying the risk factors and their weighting; these are usually obtained by stepwise logistic regression. The accuracy of probabilistic predictors can be separated into the concepts of 'overall performance', 'discrimination' and 'calibration'. Overall performance is the mathematical distance between predictions and outcomes. Discrimination is the ability of the predictor to rank order observations with different outcomes. Calibration is the correctness of prediction probabilities on an absolute scale. Statistical methods include the Brier score, coefficient of determination (Nagelkerke R2), C-statistic and regression calibration. External validation is the comparison of the actual outcomes to the predicted outcomes in a new and independent patient sample. External validation uses the statistical methods of overall performance, discrimination and calibration and is uniformly recommended before acceptance of the prediction model. Evidence from randomised controlled clinical trials should be obtained to show the effectiveness of risk scores for altering patient management and patient outcomes.

Impact of a single perioperative dose of dexamethasone on the incidence of surgical site infections: a case-control study.

AIMS: Dexamethasone is recommended in several international guidelines to prevent postoperative nausea and vomiting, a problem especially frequent in gynecological patients. Despite the increasing use of dexamethasone for this indication there are limited data concerning potential harmful effects of corticosteroids in surgical patients, especially the potential negative impact on wound healing and surgical site infection (SSI). This case-control study was conducted to look for potentially harmful effects of a single perioperative dose of dexamethasone with respect to the occurrence of SSI in gynecological and obstetric surgery patients. MATERIALS AND METHODS: We retrospectively analyzed 3449 patients undergoing inpatient gynecological or obstetric surgical procedures for the occurrence of deep SSI requiring surgical intervention or prolonged antibiotic treatment. These case patients were matched to control patients according to the surgeon performing the procedure, the type of surgery, biometric data, and known risk factors for SSI. Furthermore, timely linearity of dexamethasone use and SSI rate was exploratorily analyzed using several auto-regressive, integrated, moving-average models. RESULTS: Forty patients with deep SSI were matched to 158 controls. The risk profile for wound infections of both groups was comparable. Forty-five percent (95% confidence interval: 29-62%) of the case patients were treated with dexamethasone and 49% (95% confidence interval: 41-57%) of the control group received the drug. An increasing use of dexamethasone over time was not followed by an increased SSI rate. There were no timely correlations between dexamethasone usage and the occurrence of SSI. CONCLUSION: In this case-control study we could not detect any evidence for an increased risk for SSI after a single-dose of dexamethasone (4-8 mg) in gynecological patients.

Possibilities and limitations in the pharmacological management of postoperative nausea and vomiting.

The incidence of postoperative nausea and vomiting (PONV) after a standard anaesthetic technique consisting of inhalational anaesthetics and opioids and no PONV prophylaxis is up to 30%. Being one of the most common complaints following surgery under general anaesthesia, it is not surprising that PONV is a considerable cause of dissatisfaction with recovery from anaesthesia and remains one of the most commonly used items in surveys assessing patient satisfaction with the perioperative period and in scoring systems for the quality of recovery following anaesthesia. The weakest link in the chain from research to patient benefit is the implementation of well proven strategies. Rather than simply following existing consensus guidelines, anaesthesiologists should critically assess whether the algorithms introduced produce the desired effect. Risk-adapted strategies may work, but recent implementation studies suggest that compliance with these algorithms may be poor and that high-risk patients often do not receive appropriate antiemetic prophylaxis. Multimodal prevention may represent a more simple approach and, thus, a more reliable strategy to reduce the incidence of PONV. Such an approach would circumvent the inherent weaknesses of the need to undertake a risk assessment for each individual patient. Anaesthesiologists need to know about the new agents available to manage PONV, such as the NK1-antagonists or the newer 5-HT3 antagonists, but should not forget the traditional and well established antiemetics that are valuable components in the current portfolio. The low cost of most of the currently available antiemetics and the low incidence of side-effects suggests that a liberal antiemetic prophylaxis regimen is a meaningful option in order to eliminate or substantially reduce the 'big little problem'.

Randomised controlled trial of the effect of oral premedication with dexamethasone on hyperglycaemic response to abdominal hysterectomy.

BACKGROUND: This study was performed to evaluate the metabolic effects of a single oral dose of 8 mg dexamethasone in women undergoing hysterectomy. METHODS: Ninety non-diabetic women undergoing abdominal hysterectomy were randomised to receive 8 mg dexamethasone or placebo 2 h before surgery. Patients' perioperative care was standardised (fasting from midnight before surgery, balanced anaesthesia using propofol, fentanyl, remifentanil, cisatracurium, desflurane in oxygen/air). At five defined time points after drug administration (approximately 2, 4, 6, 10 and 14 h), blood samples were drawn under fasting conditions to measure blood glucose and free (non-esterified) fatty acids (NEFA). Data were analysed using analysis of variance for repeated measures. RESULTS: Data of 82 patients (dexamethasone: 44 and placebo: 38) were eligible for analysis. There was a statistically significant increase in blood glucose in both groups (P = 0.008). This increase was more pronounced in patients receiving dexamethasone (interaction term: P = 0.02) with maximum values at 6 h after surgery (or approximately 10 h after dexamethasone administration). There were 36 patients (placebo: 9 = 24% and dexamethasone: 27 = 61%) presenting with elevated glucose concentrations (>7 mmol l⁻¹) and 11 patients (placebo: 2 = 5% and dexamethasone: 9 = 20%) with hyperglycaemia (>8.5 mmol l⁻¹). There were no statistically significant changes in the plasma concentrations of NEFA during the perioperative period. CONCLUSION: Amounts of dexamethasone frequently used for prophylaxis of post-operative nausea and vomiting can cause short-lasting hyperglycaemia in the post-operative period, but no relevant alterations in fat metabolism. Thus, the benefits of administering corticosteroids should be weighed against the potential side-effects of short-lasting hyperglycaemia.

[Postoperative nausea and vomiting (PONV) - recommendations for risk assessment, prophylaxis and therapy - results of an expert panel meeting]. / Übelkeit und Erbrechen nach Operationen in Allgemeinanästhesie - Empfehlungen zur Risikoeinschätzung, Prophylaxe und Therapie.

BACKGROUND: The aim was to update recommendations concerning the management of postoperative nausea and vomiting (PONV) for German speaking countries. METHODS: An expert panel produced evidence-based, consented statements graded according to the Scottish Intercollegiate Guidelines Network (SIGN). RESULTS: Relevant risk factors for PONV include female gender, non-smoking status, history of PONV, history of motion sickness, use of intra- and postoperative opioids, volatile anesthetics and nitrous oxide. PONV scoring systems allow for an approximative risk assessment as a basis for a risk adapted approach. Since a risk-adapted prophylaxis vs. a risk-independent, fixed (combined) prophylaxis has not yet proven superior and because of inherent limitations of PONV scoring systems a fixed prophylaxis may be favourable. Regardless of the strategy for prophylaxis of PONV, high risk patients must be given a multimodal prophylaxis by avoiding known risk factors and applying multiple validated and effective antiemetic interventions. In the case of PONV immediate treatment is indicated due to its relevance for patients as well as the economic and medicolegal implications PONV may have. CONCLUSIONS: Given the impact of PONV on patient satisfaction and the availability of effective and safe measures to prevent and treat PONV, further efforts should be taken to actually implement present evidence in order to improve patient?s outcome following surgical procedures.

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

OBJECTIVE: In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form. METHODS: We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT3-, D2-, NK1-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia. RESULTS: 585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK1 receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing. CONCLUSIONS: There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

A simplified risk score to predict difficult intubation: development and prospective evaluation in 3763 patients.

BACKGROUND AND OBJECTIVE: Despite the presence of numerous preoperative tests to predict a difficult airway, there is no reliable bedside method. The aim of this study was to create and verify a simplified risk model with an acceptable discriminating power. METHODS: A total of 3763 patients from two university hospitals were screened for potential risk factors for difficult intubation, defined as needing additional technical or human resources, more than three attempts or duration more than 10 min. A random sample (n = 2509) was subjected to multivariate stepwise logistic regression analysis, and the most powerful independent risk factors were used to build a simplified model that was applied to a validation dataset (n = 1254). RESULTS: The following factors (odds ratio) were associated with a difficult intubation: presence of upper front teeth (3.61), history of difficult intubation (2.88), any Mallampati status different from '1' (2.55) or equal to '4' (1.91) and mouth opening less than 4 cm (1.80). The discriminating power of the score was 0.72 (95% confidence interval 0.63-0.81). The likelihood for a difficult intubation increases continuously from 0 (when no risk factor is present) to 2, 4, 8 and 17%, when one, two, three and more than three factors are present. CONCLUSION: The new simplified multivariate risk score for difficult intubation may prove to be useful in clinical practice for predicting a difficult airway. Presence of upper front teeth, a history of difficult intubation, any Mallampati status different from '1' and equal to '4' and mouth opening less than 4 cm are independent risk factors for difficult endotracheal intubation. With each of these risk factors, the likelihood increases from 0 (when no risk factor is present) to 17% (when four or five factors are present).

Risk-adapted strategy or universal multimodal approach for PONV prophylaxis?

The issue of postoperative nausea and vomiting (PONV) remains important in surgical practice, contributing to patient distress, slower recovery, and increased use of healthcare resources. Many surgical patients report it to be a worse problem than pain. Numerous findings of research indicate that PONV significantly affects patients' well-being and is among the important determinants of patient satisfaction with perioperative care. Numerous investigations have confirmed the efficacy of combining pharmacological interventions indicating that PONV is a clinical complication that is in principle avoidable. Nonetheless, PONV continues to be bothersome for too many patients. Thus, perhaps the biggest challenge across the field is to achieve a uniformly high standard of PONV management using the currently available resources. Although a risk-adapted approach has been advocated in the past, the current trend incorporated in clinical guidelines support a more liberal approach of multimodal antiemetic prevention. The current article emphasizes pros and cons of the various approaches to PONV prophylaxis and depicts most promising strategies to achieve a "PONV-free hospital."

[Postoperative nausea and vomiting. Identification of patients with risk factors for PONV]. / Für wen ist PU & E relevant--und wer ist ein Risikopatient?

This review discusses the clinical relevance of risk stratification to determine measures to prevent postoperative nausea and vomiting. The key question is whether PU&E is a problem related only to a small group of risk patients and whether risk stratification is a reasonable approach to deal with this problem. The application of risk scores to predict PU&E has been strongly advocated in the past years. These tools suggest that PU&E is mainly a problem of a small and well defined group of patients that can be identified and clearly separated from patients with no risk for PU&E. The need for applying these risk scores was based on the assumption that efficiency of antiemetic intervention mainly depends on the baseline risk for PU&E and that these are only justified at an increased risk (e.g. PU&E-risk > 60 %) where the number needed to treat is about 5 or lower. PU&E, on the other hand, are distressing and annoying symptoms for the patient. PU&E is a limiting factor for any approach to speed postoperative recovery and thus incompatible with so called fast-track rehabilitation programs. Thus, PU&E is relevant not only for high-risk patients but also for the great majority of patients with an intermediate risk for PU&E. The latter group, e.g. patients with a predicted risk to suffer from PU&E between 20 and 60 %, account for more than 80 % of all patients undergoing risk evaluation. Considering the high impact of PU&E for the individual patient, the small incidence of patients where the occurrence of PU&E can be ruled out with appropriate high probability, and finally the availability of several effective antiemetic measures all with a marked low incidence of side-effects, the authors of this review advocate a liberal policy for prophylactic administration of antiemetics. Prophylaxis against PU&E should be as self-evident as measures to limit postoperative pain. Omitting antiemetic prevention should only be considered if the estimated risk for PU&E is extremely low. All other patients in whom PU&E cannot be ruled out with high confidence should receive routine antiemetic prophylaxis.

Cafedrine/Theodrenaline (20:1) Is an Established Alternative for the Management of Arterial Hypotension in Germany-a Review Based on a Systematic Literature Search.

A 20:1 combination of cafedrine:theodrenaline (Akrinor®) is widely used in Germany for the treatment of hypotensive states during anesthesia and in emergency medicine. Although this drug formulation has been available since 1963, there are few studies relating to its use and many of the data are only available in German. In this article, we summarize the available data and propose mechanisms for the effects of cafedrine/theodrenaline on cardiac muscle cells and vascular smooth muscle cells. Cafedrine/theodrenaline leads to a rapid increase in mean arterial pressure that is characterized by increased cardiac preload, stroke volume, and cardiac output. Systemic vascular resistance and heart rate remain mostly unchanged. Factors which impact the effects of cafedrine/theodrenaline are gender, high arterial pressure at baseline, use of ß-blockers, and heart failure. Importantly, the drug is frequently used in obstetric anesthesia without detrimental effects on umbilical cord pH or APGAR score.

Systematic review on the recurrence of postoperative nausea and vomiting after a first episode in the recovery room - implications for the treatment of PONV and related clinical trials.

BACKGROUND: Despite the presence of a plethora of publications on the prevention of postoperative nausea and vomiting (PONV) only little is known how to treat established symptoms. Besides the high effort of performing these efficacy trials (much more patients must give their consent than are actually included in a study) and ethical concerns, little is known about the rate of re-occurring PONV/vomiting after placebo. As a consequence investigators will have difficulties defining a clinically relevant effect for the new treatment which is crucial for any planning. A quantitative systematic review was performed in order to provide more reliable estimates of the incidence of re-occurring PONV/vomiting after placebo and to help investigators defining a clinically relevant treatment effect. METHODS: A systematic search of the literature was performed using an extended search strategy of a previous review. Data on the recurrence of PONV (any nausea or emetic symptom) and vomiting (retching or vomiting) was extracted from published reports treating PONV with placebo and unpublished results from two observational trials where no treatment was given. A nonlinear random effects model was used to calculate estimates of the recurrence of symptoms and their 95%-confidence intervals (95%-CI). RESULTS: A total of 29 trials (including the unpublished data) were eligible for the calculations. Depending on the length of observation after administering placebo or no treatment the recurrence rate of PONV was between 65% (95%-CI: 53%...75%) and 84% (95%-CI: 73%...91%) and that of vomiting was between 65% (95%-CI: 44%...81%) and 78% (95%-CI: 59%...90%). CONCLUSION: Almost all trials showed a considerable and consistently high rate of recurrence of emetic symptoms after placebo highlighting the need for a consequent antiemetic treatment. Future (placebo) controlled efficacy trials may use the presented empirical estimates for defining clinically relevant effects and for statistical power considerations.