Systematic review and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: patient comfort.

BACKGROUND: Maximising patient comfort during and after surgery is a primary concern of anaesthetists and other perioperative clinicians, but objective measures of what constitutes patient comfort in the perioperative period remain poorly defined. The Standardised Endpoints in Perioperative Medicine initiative was established to derive a set of standardised endpoints for use in perioperative clinical trials. METHODS: We undertook a systematic review to identify measures of patient comfort used in the anaesthetic, surgical, and other perioperative literature. A multi-round Delphi consensus process that included up to 89 clinician researchers was then used to refine a recommended list of outcome measures. RESULTS: We identified 122 studies in a literature search, which were the basis for a preliminary list of 24 outcome measures and their definitions. The response rates for Delphi Rounds 1, 2, and 3 were 100% (n=22), 90% (n=79), and 100% (n=13), respectively. A final list of six defined endpoints was identified: pain intensity (at rest and during movement) at 24 h postoperatively, nausea and vomiting (0-6 h, 6-24 h, and overall), one of two quality-of-recovery (QoR) scales (QoR score or QoR-15), time to gastrointestinal recovery, time to mobilisation, and sleep quality. CONCLUSIONS: As standardised outcomes will support benchmarking and pooling (meta-analysis) of trials, one or more of these recommended endpoints should be considered for inclusion in clinical trials assessing patient comfort and pain after surgery.

Effect of sufentanil on bispectral index in the elderly.

We examined the impact of adding sufentanil during anaesthesia induction with propofol on bispectral index values in elderly patients (≥ 65 years). Patients were randomly assigned to receive a target-controlled sufentanil infusion (effect-site concentration of 0.3 ng.ml-1 ) or matching placebo, followed by a target-controlled propofol induction (initial effect-site concentration of 0.5 µg.ml-1 ; step-wise increase of 0.5 µg.ml-1 ) until loss of consciousness defined as an Observer's Assessment of Alertness/Sedation score < 2. Seventy-one patients (sufentanil 35, placebo 36) completed the study. Mean (SD) age was 72.3 (5.8) years; 41% were women. At loss of consciousness, mean (SD) bispectral index value was 75.0 (8.6) with sufentanil and 70.0 (8.0) with placebo; mean difference -5.0 (95% confidence interval -8.9 to -1.1), p = 0.013. Post-hoc analyses suggest that the difference was significant in men only (mean difference -7.3 (-11.8 to -2.6), p = 0.003). Sufentanil co-induction with propofol results in higher bispectral index values at loss of consciousness in elderly patients.

Alternative intubation techniques vs Macintosh laryngoscopy in patients with cervical spine immobilization: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Immobilization of the cervical spine worsens tracheal intubation conditions. Various intubation devices have been tested in this setting. Their relative usefulness remains unclear. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for randomized controlled trials comparing any intubation device with the Macintosh laryngoscope in human subjects with cervical spine immobilization. The primary outcome was the risk of tracheal intubation failure at the first attempt. Secondary outcomes were quality of glottis visualization, time until successful intubation, and risk of oropharyngeal complications. RESULTS: Twenty-four trials (1866 patients) met inclusion criteria. With alternative intubation devices, the risk of intubation failure was lower compared with Macintosh laryngoscopy [risk ratio (RR) 0.53; 95% confidence interval (CI) 0.35-0.80]. Meta-analyses could be performed for five intubation devices (Airtraq, Airwayscope, C-Mac, Glidescope, and McGrath). The Airtraq was associated with a statistically significant reduction of the risk of intubation failure at the first attempt (RR 0.14; 95% CI 0.06-0.33), a higher rate of Cormack-Lehane grade 1 (RR 2.98; 95% CI 1.94-4.56), a reduction of time until successful intubation (weighted mean difference -10.1 s; 95% CI -3.2 to -17.0), and a reduction of oropharyngeal complications (RR 0.24; 95% CI 0.06-0.93). Other devices were associated with improved glottis visualization but no statistically significant differences in intubation failure or time to intubation compared with conventional laryngoscopy. CONCLUSIONS: In situations where the spine is immobilized, the Airtraq device reduces the risk of intubation failure. There is a lack of evidence for the usefulness of other intubation devices.

Ventilation strategies in obese patients undergoing surgery: a quantitative systematic review and meta-analysis.

BACKGROUND: Pathophysiological changes due to obesity may complicate mechanical ventilation during general anaesthesia. The ideal ventilation strategy is expected to optimize gas exchange and pulmonary mechanics and to reduce the risk of respiratory complications. METHODS: Systematic search (databases, bibliographies, to March 2012, all languages) was performed for randomized trials testing intraoperative ventilation strategies in obese patients (BMI ≥ 30 kg m(-2)), and reporting on gas exchange, pulmonary mechanics, or pulmonary complications. Meta-analyses were performed when data from at least three studies or 100 patients could be combined. RESULTS: Thirteen studies (505 obese surgical patients) reported on a variety of ventilation strategies: pressure- or volume-controlled ventilation (PCV, VCV), various tidal volumes, and different PEEP or recruitment manoeuvres (RM), and combinations thereof. Definitions and reporting of endpoints were inconsistent. In five trials (182 patients), RM added to PEEP compared with PEEP alone improved intraoperative PaO2/FIO2 ratio [weighted mean difference (WMD), 16.2 kPa; 95% confidence interval (CI), 8.0-24.4] and increased respiratory system compliance (WMD, 14 ml cm H(2)O(-1); 95% CI, 8-20). Arterial pressure remained unchanged. In four trials (100 patients) comparing PCV with VCV, there was no difference in PaO2/FIO2 ratio, tidal volume, or arterial pressure. Comparison of further ventilation strategies or combination of other outcomes was not feasible. Data on postoperative complications were seldom reported. CONCLUSIONS: The ideal intraoperative ventilation strategy in obese patients remains obscure. There is some evidence that RM added to PEEP compared with PEEP alone improves intraoperative oxygenation and compliance without adverse effects. There is no evidence of any difference between PCV and VCV.

Intravenous lidocaine has no impact on rocuronium-induced neuromuscular block. Randomised study.

BACKGROUND: Intravenous lidocaine is increasingly used in surgical patients. As it has neuromuscular blocking effects, we tested the impact of an intravenous lidocaine infusion on the time course of a rocuronium-induced neuromuscular block. METHODS: Fifty-two adults undergoing surgery were randomly allocated to intravenous lidocaine 1.5 mg/kg followed by a continuous infusion of 2 mg/kg/h or physiological saline (control) throughout surgery. Anaesthesia was induced and maintained with a target-controlled propofol infusion and sufentanil. After loss of consciousness, rocuronium 0.6 mg/kg was given. Neuromuscular transmission was measured using train-of-four (TOF)-watch SX (Organon, Swords Co., Dublin, Ireland) acceleromyography. RESULTS: Onset time (to 95% depression of first twitch) was on average 113.9 s (standard deviation 35.3) with lidocaine and 119.5 s (44.9) with saline (P = 0.618). Total recovery time (TOF ratio 0.9) was on average 58.1 min (15.1) with lidocaine and 54.3 min (16.9) with saline (P = 0.394). Clinical duration (until first twitch has recovered to 25%) was on average 33.3 min (7.2) with lidocaine and 30.6 min (8.1) with saline (P = 0.21). Recovery index (time between 25% and 75% recovery of the first twitch) was on average 11.5 min (5.0) with lidocaine and 10.6 min (4.1) with saline (P = 0.458). Recovery time (between 25% recovery of the first twitch and TOF ratio 0.9) was on average 24.8 min (9.3) with lidocaine and 23.2 min (9.2) with saline (P = 0.541). CONCLUSION: A continuous intravenous infusion of lidocaine has no impact on the time course of the neuromuscular blockade induced by a standard intubation dose of rocuronium.

[Evidence-based anesthesiology: knowledge transfer from research into clinical practice]. / Evidenzbasierte Anästhesiologie : Wissenstransfer aus der Forschung in die klinische Praxis.

In the interest of patients evidence-based healthcare should be provided and is increasingly being demanded worldwide. In the daily medical practice however, healthcare based on proven scientific findings has not yet become firmly established. There are several causes for this. Problems occur at the level of knowledge generation, knowledge transfer from research into practice and also at the individual level of the treating healthcare professional. Nowadays, with a rapidly growing amount of knowledge it is almost impossible for the individual to quickly filter out the relevant facts. This article aims to shed light on the various aspects of the process of knowledge transfer from a clinical trial to evidence-based guidelines. It will make the reader aware of potential problems during this process and show some feasible approaches to solving them. Wherever possible, the field of anesthesiology will be used as the reference point. Evidence-based information sources will be presented and advice on how to use them will be given.

Time course of rocuronium-induced neuromuscular block after pre-treatment with magnesium sulphate: a randomised study.

BACKGROUND: A previously published study suggested that pre-treatment with magnesium sulphate (MgSO(4)) had no impact on the speed of onset of rocuronium-induced neuromuscular block. We set out to verify this assumption. METHODS: Eighty patients (18-60 years) were randomly allocated to MgSO(4) 60 mg/kg or placebo (saline). Study drugs were given intravenously for 15 min before induction of anaesthesia with propofol, sufentanil and rocuronium 0.6 mg/kg. Anaesthesia was maintained with a target-controlled propofol infusion. Neuromuscular transmission was measured using train-of-four (TOF)-Watch SX acceleromyography. RESULTS: Onset was analysed in 37 MgSO(4) and 38 saline patients, and recovery in 35 MgSO(4) and 37 saline patients. Onset time (to 95% depression of T1) was on average 77 [SD=18] s with MgSO(4) and 120 [48] s with saline (P<0.001). The total recovery time (DurTOF0.9) was on average 73.2 [22] min with MgSO(4) and 57.8 [14.2] min with saline (P<0.003). The clinical duration (Dur25%) was on average 44.7 [14] min with MgSO(4) and 33.2 [8.1] min with saline (P<0.0002). The recovery index (Dur25-75%) was on average 14.0 [6] min with MgSO(4) and 11.2 [5.2] min with saline (P<0.02). The recovery time (Dur25%TOF0.9) was on average 28.5 [11.7] min with MgSO(4) and 24.7 [8.4] min with saline (P=0.28). CONCLUSION: Magnesium sulphate given 15 min before propofol anaesthesia reduces the onset time of rocuronium by about 35% and prolongs the total recovery time by about 25%.

Bispectral and spectral entropy indices at propofol-induced loss of consciousness in young and elderly patients.

BACKGROUND: Bispectral (BIS) and state/response entropy (SE/RE) indices have been widely used to estimate depth of anaesthesia and sedation. In adults, independent of age, adequate and safe depth of anaesthesia for surgery is usually assumed when these indices are between 40 and 60. Since the EEG is changing with increasing age, we investigated the impact of advanced age on BIS, SE, and RE indices during induction. METHODS: BIS and SE/RE indices were recorded continuously in elderly (> or =65 yr) and young (< or =40 yr) surgical patients who received propofol until loss of consciousness (LOC) using stepwise increasing effect-site concentrations. LOC was defined as an observer assessment of alertness/sedation score <2, corresponding to the absence of response to mild prodding or shaking. RESULTS: We analysed 35 elderly [average age, 78 yr (range, 67-96)] and 34 young [35 (19-40)] patients. At LOC, all indices were significantly higher in elderly compared with young patients: BIS(LOC), median 70 (range, 58-91) vs 58 (40-70); SE(LOC), 71 (31-88) vs 55.5 (23-79); and RE(LOC), 79 (35-96) vs 59 (25-80) (P<0.001 for all comparisons). With all three monitors, only a minority of elderly patients lost consciousness within a 40-60 index range: two (5.7%) with BIS and RE each, and seven (20%) with SE. In young patients, the respective numbers were 20 (58.8%) for BIS, 13 (38.2%) for SE, and nine (26.5%) for RE. CONCLUSIONS: In adults undergoing propofol induction, BIS, SE, and RE indices at LOC are significantly affected by age.

Benefit and risk of intrathecal morphine without local anaesthetic in patients undergoing major surgery: meta-analysis of randomized trials.

Intrathecal morphine without local anaesthetic is often added to a general anaesthetic to prevent pain after major surgery. Quantification of benefit and harm and assessment of dose-response are needed. We performed a meta-analysis of randomized trials testing intrathecal morphine alone (without local anaesthetic) in adults undergoing major surgery under general anaesthesia. Twenty-seven studies (15 cardiac-thoracic, nine abdominal, and three spine surgery) were included; 645 patients received intrathecal morphine (dose-range, 100-4000 microg). Pain intensity at rest was decreased by 2 cm on the 10 cm visual analogue scale up to 4 h after operation and by about 1 cm at 12 and 24 h. Pain intensity on movement was decreased by 2 cm at 12 and 24 h. Opioid requirement was decreased intraoperatively, and up to 48 h after operation. Morphine-sparing at 24 h was significantly greater after abdominal surgery {weighted mean difference, -24.2 mg [95% confidence interval (CI) -29.5 to -19.0]}, compared with cardiac-thoracic surgery [-9.7 mg (95% CI -17.6 to -1.80)]. The incidence of respiratory depression was increased with intrathecal morphine [odds ratio (OR) 7.86 (95% CI 1.54-40.3)], as was the incidence of pruritus [OR 3.85 (95% CI 2.40-6.15)]. There was no evidence of linear dose-responsiveness for any of the beneficial or harmful outcomes. In conclusion, intrathecal morphine decreases pain intensity at rest and on movement up to 24 h after major surgery. Morphine-sparing is more pronounced after abdominal than after cardiac-thoracic surgery. Respiratory depression remains a major safety concern.

Nefopam for the prevention of postoperative pain: quantitative systematic review.

Nefopam, a centrally acting analgesic, has been used in the surgical setting in many countries since the mid-1970s. However, clinical trials provide contflicting results for its analgesic potency. We performed a systematic search (multiple databases, bibliographies, any language, to January 2008) for randomized, placebo-controlled trials of nefopam for the prevention of postoperative pain. Data were combined using classic methods of meta-analyses and were expressed as weighted mean difference (WMD), relative risk (RR), and number needed to treat/harm (NNT/H) with 95% confidence interval (CI). Nine trials (847 adult patients, 359 received nefopam) were included. Nefopam (cumulative doses, 20-160 mg) was given orally or i.v., as single or multiple doses, or as a continuous infusion. Compared with placebo, cumulative 24 h morphine consumption was decreased with nefopam: WMD -13 mg (95% CI -17.9 to -8.15). Pain intensity at 24 h was also decreased: on a 100 mm visual analogue scale, WMD -11.5 mm (95% CI -15.1 to -7.85). The incidence of tachycardia was increased with nefopam (RR 3.12, 95% CI 1.11-8.79; NNH 7), as was the incidence of sweating (RR 4.92, 95% CI 2.0-12.1; NNH 13). There is limited evidence from the published literature that nefopam may be a useful non-opioid analgesic in surgical patients. The analgesic potency seems to be similar to non-steroidal anti-inflammatory drugs. However, dose responsiveness and adverse effect profile remain unclear, and the role of nefopam as part of multimodal analgesia needs to be established. Data in children are lacking.

Algorithms for the prevention of postoperative nausea and vomiting: an efficacy and efficiency simulation.

BACKGROUND AND OBJECTIVE: A number of algorithms for the prevention of postoperative nausea and vomiting have been proposed. Their efficacy and efficiency remains unclear. METHODS: We assumed that four antiemetic interventions were similarly effective and achieved additive effects when combined. We applied published and hypothetical algorithms for the prevention of postoperative nausea and vomiting to patient populations with different baseline risks. As indicators of efficacy and efficiency we computed for each baseline risk and each algorithm the total number of patients receiving prophylaxis, the total number of administered interventions, the cumulative 24 h incidence of postoperative nausea and vomiting, and an Efficiency Index (i.e. the number of administered interventions divided by the achieved absolute risk reduction). This was done for cohorts of 100 patients. RESULTS: Ten algorithms were tested in seven populations with different baseline risks. Algorithms were fixed (> or = 1 intervention given to all patients, independent of baseline risk) or risk-adapted (> or = 1 intervention administered depending on the presumed baseline risk). Risk-adapted algorithms were escalating (the greater the baseline risk, the more interventions are given) or dichotomous (a fixed number of interventions is given to high-risk patients only). With some algorithms, when applied to selected patient populations, the average postoperative nausea and vomiting incidence could be decreased below 15%; however, none produced consistent postoperative nausea and vomiting incidences below 20% across all populations. With all, the number of administered antiemetic interventions was the major factor for improved efficacy. Depending on the baseline risk, some algorithms offered potential towards improved efficiency. CONCLUSIONS: Despite improved knowledge on risk factors and antiemetic strategies, none of the tested algorithms completely prevents postoperative nausea and vomiting and none is universally applicable. Anesthesiologists should try to identify the most useful antiemetic strategy for a specific setting. That strategy may be prophylactic or therapeutic or a combination of both, and it should consider institutional policies and individual baseline risks.

Impact of the intubation model on the efficacy of rocuronium during rapid sequence intubation: systematic review of randomized trials.

BACKGROUND: Propofol-rocuronium is thought to be superior to thiopental-rocuronium for rapid sequence intubation (RSI). The role of the intubation model per se has never been investigated. METHODS: Randomized comparisons of rocuronium with succinylcholine for true RSI (administration of muscle relaxant immediately after the hypnotic, intubation within 60 s) or modified RSI (delay between administration of the hypnotic and the muscle relaxant, intubation within 60 s) were sought. Good or excellent intubation conditions were expressed as relative risks (RR) with 95% confidence intervals (CI). RESULTS: Twelve trials (1,471 patients) used a true RSI. With propofol for induction, RR for good or excellent intubation conditions with conventional rocuronium doses (0.6-0.7 mg/kg) was 0.95 (95%CI, 0.90-1.00), with high doses (0.9-1.2 mg/kg) was 0.96 (0.92-1.01) compared with succinylcholine. With thiopental for induction, RR with conventional rocuronium doses was 0.69 (0.61-0.78) and with high doses was 0.99 (0.95-1.03). Nine trials (340 patients) used a modified RSI. With propofol for induction, RR with conventional rocuronium doses was 0.98 (0.91-1.06); data on high rocuronium doses were lacking. With thiopental for induction, RR with conventional rocuronium doses was 0.97 (0.92-1.02) and with high doses was 1.0. There was no evidence that concomitantly used opioids or the dose of the induction agent had an impact on intubation conditions, independent of the intubation model. CONCLUSION: The efficacy of rocuronium for RSI is influenced by both, the induction agent and the intubation model. To test the clinical usefulness of alternatives to succinylcholine for RSI, a true RSI model should be used.

[Prevention and treatment of postoperative nausea and vomiting in children. An evidence-based approach]. / Prévention et traitement des nausées et vomissements postopératoires chez l'enfant: une approche basée sur les preuves.

Significant improvement towards an efficacious control of postoperative nausea and vomiting (PONV) has taken place recently. These improvements may be summarised using the "rule of three". That rule describes a pragmatic and rational approach of PONV control. First, identify the patient at risk using predictive factors. Second, modify the anaesthesia technique to keep the baseline risk as low as possible. Third, administer antiemetics rationally, considering their degree of efficacy, their risk, and their potential additive effects. Despite considerable research efforts, identifying the patient at high risk of PONV remains a difficult task. However, today, we understand the degree of efficacy, dose-responsiveness, and adverse effects of most antiemetics. None of those molecules should be regarded as being universally efficacious, there is no gold standard, and, when used alone, their degree of efficacy is limited. Thus, they should be combined for improved efficacy. Among the most promising molecules are butyrophenones (droperidol, haloperidol), 5-HT(3) receptor antagonists (ondansetron, dolasetron, tropisetron, granisetron), and steroids (for instance, dexamethasone). The lack of relevant paediatric PONV data remains a major drawback and is highly unsatisfactory. Hopefully, future research will further improve the control of PONV not only in adults but also in children.

[Postoperative nausea and vomiting]. / Postoperative Ubelkeit und Erbrechen.

The rule of three describes three steps which are needed for an optimal control of postoperative nausea and vomiting (PONV). Firstly, patients at high risk of PONV need to be identified. Knowledge about predictive factors may help to identify patients who may best profit from prophylaxis and those where prophylaxis is not worthwhile since the baseline risk is too low. Secondly, for high-risk patients a low emetogenic anaesthesia technique should be chosen, and thirdly, these patients should additionally receive a prophylactic antiemetic cocktail. At present, butyrophenones (e.g. droperidol), 5-HT(3) receptor antagonists ("setrons") and steroids (e.g. dexamethasone) are the most rational choices for the antiemetic cocktail. Although there is strong evidence that there is an additive effect when these antiemetics are combined, economic constraints may influence the number of antiemetics that are eventually chosen. Identification of high-risk patients remains the most difficult part of the rule of three. Risk scores have been proposed and have been widely implemented in clinical practice. The sensitivity and specificity of such scores, however, remain particularly unsatisfactory. Unless more reliable risk scores are developed, aggressive treatment of established PONV symptoms may be more useful and more cost-effective than prophylaxis for many patients.

The effect of cigarette smoking on the hypnotic efficacy of propofol.

The bispectral index (BIS) was used to examine the hypnotic efficacy of propofol in 25 smokers (20 cigarettes/day for 2 years) and 24 matched non-smokers (same gender, age, height, weight). BIS was recorded at baseline, at four incremental effect-site concentrations of propofol and at loss of consciousness. Compared with non-smokers, smokers were found to have higher BIS values at baseline (mean (SD)) (97 (1) vs 98 (1)), at 0.7 microg x ml(-1) (95 (3) vs 97 (1)) and at 1.1 microg x ml(-1) (89 (6) vs 94 (4)), p = 0.0099, and they lost consciousness at higher propofol concentrations (2.0 (0.4) vs 2.4 (0.8) microg x ml(-1)), p = 0.03, and at lower BIS values (66 (10) vs 60 (10)), p = 0.04. The hypnotic efficacy of propofol is reduced when used at low effect-site concentrations in smokers. This phenomenon may have some impact on the management of smokers undergoing sedation using target controlled infusion systems.

[Cochrane Anaesthesia Review Group and the Cochrane Library. Useful resources for anaesthetists]. / Cochrane-Anästhesie-Gruppe und Cochrane-Bibliothek. Nützliche Ressourcen für den Anästhesisten.

The Cochrane Collaboration is an international non-profit organisation that aims to help clinicians in making well-informed decisions about health care issues. This is done through preparing, maintaining and disseminating systematic reviews on the effects of health care interventions. To facilitate this task, review groups have been established. These groups cover specific health care areas and form the organisational basis of the collaboration. They provide methodological and logistic help to the authors of the systematic reviews. The Cochrane Anaesthesia Review Group (CARG) covers anaesthesia, perioperative medicine, intensive care,pre-hospital medicine, resuscitation, and emergency medicine. Protocols and completed Cochrane reviews are published in a structured format in the electronic Cochrane Library. Beside this Cochrane database of systematic reviews, the Cochrane library contains a database with summaries of non-Cochrane systematic reviews (database of abstracts of reviews of effectiveness), and a comprehensive database with controlled clinical trials (Cochrane central register of controlled trials). Thus the Cochrane library is a useful source of information on health care interventions for anaesthetists.

[Evidence-based medicine and the systematic review in perioperative medicine]. / Evidence-based Medicine und systematische Reviews in der perioperativen Medizin. Modeerscheinung oder Notwendigkeit?

The aim of Evidence-based medicine (EBM) is the unbiased and systematic identification and synthesis of valid scientific data. These best-evidence data may then be used for clinical decision-making. The systematic review is the most important tool of EBM and gives a specific answer to a specific question. More than 200 systematic reviews have been published in perioperative medicine. They treat complications and risks related to anaesthesia, postoperative and labour analgesia, nausea and vomiting, regional anaesthesia, blood transfusion and fluids replacement, and resuscitation. The majority of these systematic reviews are of good quality. In the specific settings of perioperative medicine the number of systematic reviews has become so important that recommendations for evidenced-based strategies of prevention and therapy can be formulated.