Predictors for postoperative nausea and vomiting after xenon-based anaesthesia.

BACKGROUND: In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia. METHODS: With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication. RESULTS: Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P<0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59). CONCLUSIONS: The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia. CLINICAL TRIAL REGISTRATION: German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

Hypercapnia and surgical site infection: a randomized trial.

BACKGROUND: Tissue oxygenation is a strong predictor of surgical site infection (SSI). Mild intraoperative hypercapnia increases peripheral, gastrointestinal, and splanchnic tissue oxygenation and perfusion. Hypercapnia also has anti-inflammatory effects. However, it is unknown whether hypercapnia reduces SSI risk. We tested the hypothesis that mild intraoperative hypercapnia reduces the risk of SSI in patients having colon resection surgery. METHODS: With institutional review board approval and subject consent, patients having elective colon resection (e.g. hemicolectomy and low-anterior resection) expected to last >2 h were randomly assigned to intraoperative normocapnia (PE'CO2 ≈ 35 mm Hg; n=623) or hypercapnia ( PE'CO2 ≈ 50 mm Hg; n=592). Investigators blinded to group assignment evaluated perioperative SSI (Center for Disease Control criteria) for 30 postoperative days. SSI rates were compared. RESULTS: Patient and surgical characteristics were comparable among the groups. The SSI rate for normocapnia was 13.3%, and for hypercapnia, it was 11.2% (P=0.29). The Executive Committee stopped the trial after the first a priori determined statistical assessment point because of much smaller actual effect compared with the projected. However, because the actual difference found in the SSI rates (15-16%) were within the 95% confidence intervals (CIs) of the projected relative difference of 33% (95% CI -43 to +24%), our results cannot be considered as 'no difference', and cannot exclude a Type II error. Time to first bowel movement was half-a-day shorter in the hypercapnia group. CONCLUSIONS: Mild hypercapnia appears to have little or-possibly-no ability to prevent SSI after colon resection. Other strategies for reducing SSI risk should thus take priority.

Evidence-based analysis of risk factors for postoperative nausea and vomiting.

BACKGROUND: /st> In assessing a patient's risk for postoperative nausea and vomiting (PONV), it is important to know which risk factors are independent predictors, and which factors are not relevant for predicting PONV. METHODS: /st> We conducted a systematic review of prospective studies (n>500 patients) that applied multivariate logistic regression analyses to identify independent predictors of PONV. Odds ratios (ORs) of individual studies were pooled to calculate a more accurate overall point estimate for each predictor. RESULTS: /st> We identified 22 studies (n=95 154). Female gender was the strongest patient-specific predictor (OR 2.57, 95% confidence interval 2.32-2.84), followed by the history of PONV/motion sickness (2.09, 1.90-2.29), non-smoking status (1.82, 1.68-1.98), history of motion sickness (1.77, 1.55-2.04), and age (0.88 per decade, 0.84-0.92). The use of volatile anaesthetics was the strongest anaesthesia-related predictor (1.82, 1.56-2.13), followed by the duration of anaesthesia (1.46 h(-1), 1.30-1.63), postoperative opioid use (1.39, 1.20-1.60), and nitrous oxide (1.45, 1.06-1.98). Evidence for the effect of type of surgery is conflicting as reference groups differed widely and funnel plots suggested significant publication bias. Evidence for other potential risk factors was insufficient (e.g. preoperative fasting) or negative (e.g. menstrual cycle). CONCLUSIONS: /st> The most reliable independent predictors of PONV were female gender, history of PONV or motion sickness, non-smoker, younger age, duration of anaesthesia with volatile anaesthetics, and postoperative opioids. There is no or insufficient evidence for a number of commonly held factors, such as preoperative fasting, menstrual cycle, and surgery type, and using these factors may be counterproductive in assessing a patient's risk for PONV.

Supplemental intravenous crystalloids for the prevention of postoperative nausea and vomiting: quantitative review.

Hypovolaemia after overnight fasting is believed to exacerbate postoperative nausea and vomiting (PONV). However, data on the efficacy of supplemental i.v. crystalloids for PONV prophylaxis are conflicting. We performed a literature search using CENTRAL, MEDLINE, EMBASE, CINAHL, and Web of Science. We included prospective randomized controlled trials that reported PONV event rates in patients receiving supplemental i.v. crystalloids or a conservative fluid regimen after elective surgery under general anaesthesia. Studies were evaluated with regard to random sequence generation, allocation concealment, blinding of participants, personnel, and outcome assessment, incomplete outcome data, and selective reporting. We identified 15 trials (n=787 crystalloids; n=783 conservative fluids). Compared with conservative fluids, i.v. crystalloids reduced the risk of early postoperative nausea (PON) (relative risk 0.73, 95% confidence interval 0.59-0.89; P=0.003), late PON (0.41, 0.22-0.76; P=0.004), and overall PON (0.66, 0.46-0.95; P=0.02). I.V. crystalloids did not reduce the risk of early postoperative vomiting (POV) (0.66, 0.37-1.16; P=0.16) or late POV (0.52, 0.25-1.11; P=0.09), but did reduce overall POV (0.48, 0.29-0.79; P=0.004). I.V. crystalloids did not reduce the risk of early PONV (0.74, 0.49-1.12; P=0.16), but did reduce the risk of late PONV (0.27, 0.13-0.54; P<0.001) and overall PONV (0.59, 0.42-0.84; P=0.003). I.V. crystalloids reduced the need for antiemetic rescue treatment (0.56, 0.45-0.68; P<0.001). In summary, supplemental i.v. crystalloids were associated with a lower incidence of several PONV outcomes. However, a number of PONV outcomes failed to reach statistical significance, perhaps due to the lack of power. Thus, studies sufficiently powered for the less frequent outcomes (e.g. POV) are required.

Cisplatin-induced emesis: systematic review and meta-analysis of the ferret model and the effects of 5-HT3 receptor antagonists.

PURPOSE: The ferret cisplatin emesis model has been used for ~30 years and enabled identification of clinically used anti-emetics. We provide an objective assessment of this model including efficacy of 5-HT3 receptor antagonists to assess its translational validity. METHODS: A systematic review identified available evidence and was used to perform meta-analyses. RESULTS: Of 182 potentially relevant publications, 115 reported cisplatin-induced emesis in ferrets and 68 were included in the analysis. The majority (n = 53) used a 10 mg kg⁻¹ dose to induce acute emesis, which peaked after 2 h. More recent studies (n = 11) also used 5 mg kg⁻¹, which induced a biphasic response peaking at 12 h and 48 h. Overall, 5-HT3 receptor antagonists reduced cisplatin (5 mg kg⁻¹) emesis by 68% (45-91%) during the acute phase (day 1) and by 67% (48-86%) and 53% (38-68%, all P < 0.001), during the delayed phase (days 2, 3). In an analysis focused on the acute phase, the efficacy of ondansetron was dependent on the dosage and observation period but not on the dose of cisplatin. CONCLUSION: Our analysis enabled novel findings to be extracted from the literature including factors which may impact on the applicability of preclinical results to humans. It reveals that the efficacy of ondansetron is similar against low and high doses of cisplatin. Additionally, we showed that 5-HT3 receptor antagonists have a similar efficacy during acute and delayed emesis, which provides a novel insight into the pharmacology of delayed emesis in the ferret.

Documentation of post-operative nausea and vomiting in routine clinical practice.

This study investigated the quality of documentation of post-operative nausea and vomiting (PONV) by comparing incidences collected by a research team with those reported routinely by nursing personnel. A total of 560 patients passing through an interdisciplinary recovery room were included in the study. The overall recorded incidence of PONV over 24 h was 30.7%, which was in agreement with the predicted value of 32% calculated using incidences from published randomized controlled trials. Out of the total number of 86 cases of PONV in the recovery room only 36 (42%) were detected by nursing staff. Similarly, out of the total number of 129 cases of PONV on the ward over 24 h, only 37 (29%) were recognized by nursing staff during routine care. In conclusion, PONV in routine clinical care is likely to be under-reported. To use PONV as a valid quality measure, patients need to be actively asked about nausea and vomiting at frequent intervals in a standardized fashion. A considerable proportion of patients experience PONV after discharge from the recovery room, so the assessment of PONV should cover at least 24 h post-operatively.

Prevention of postdural puncture headache after accidental dural puncture: a quantitative systematic review.

No clear consensus exists on how to best prevent severe headache from occurring after accidental dural puncture. We conducted a quantitative systematic review to identify all available evidence for the prevention of postdural puncture headache (PDPH) and included 17 studies with 1264 patients investigating prophylactic epidural blood patch (PEBP), epidural morphine, intrathecal catheters, and epidural or intrathecal saline. The relative risk (RR) for headache after PEBP was 0.48 [95% confidence interval (CI): 0.23-0.99] in five non-randomized controlled trials (non-RCTs) and 0.32 (0.10-1.03) in four randomized controlled trials (RCTs). The RR for epidural morphine (based on a single RCT) was 0.25 (0.08-0.78). All other interventions were based on non-RCTs and failed statistical significance, including long-term intrathecal catheters with an RR of 0.21 (0.02-2.65). There are a number of promising options to prevent PDPH, yet heterogeneity between the studies and publication bias towards small non-RCTs with positive results limits the available evidence. Thus, a large multicentre RCT is needed to determine the best preventative practices.

Evaluation of bispectral index and auditory evoked potentials for hypnotic depth monitoring during balanced xenon anaesthesia compared with sevoflurane.

BACKGROUND: None of the currently available hypnosis monitoring systems have evaluated balanced xenon anaesthesia. We investigated the performance of the bispectral index (BIS) and the composite A-line autoregressive index (cAAI) while comparing balanced xenon with sevoflurane anaesthesia. METHODS: Sixty patients undergoing elective abdominal surgery participated in this registered double-blinded, controlled trial and-after written informed consent-were randomly assigned to one of the study groups (xenon, n=30; sevoflurane, n=30). After induction, general anaesthesia was maintained with xenon 60% or sevoflurane 2.0% in 30% O2. Remifentanil was titrated to clinical needs. BIS and cAAI values were recorded electronically and blinded to the performing physician. Emergence from anaesthesia was evaluated and during 12 h follow-up, patients were questioned twice for signs of recalls. RESULTS: During induction and maintenance of anaesthesia, BIS values in the xenon group were comparable with sevoflurane anaesthesia and within the recommended range. Although the cAAI remained stable in the sevoflurane group, values increased during balanced xenon anaesthesia and exceeded the recommended upper limit after 65 min. Emergence from xenon anaesthesia was significantly faster than from sevoflurane (eye opening at 3.8 vs 10.3 min, P<0.001), and BIS values were concordant with the washout of both anaesthetics. No incident of recall was reported. CONCLUSIONS: During surgery, xenon/remifentanil anaesthesia can be monitored using BIS and cAAI. However, cAAI values changed after about 1 h of anaesthesia. Further studies will be needed to address the question whether auditory signal processing is altered during extended xenon exposure.

The unrecognised difficult extubation: a call for vigilance.

Tracheal extubation remains a critical and often overlooked period of difficult airway management. A 66-year-old man, scheduled for C5-C7 anterior fusion, with an easy view of the vocal cords, presented with a sublaryngeal obstruction that required a reduced tracheal tube size. Despite correct tube placement, intra-operative ventilation remained difficult. At the end of surgery a pulsatile tracheal compression was fibreopticially observed above the carina. After discussion with the attending otolaryngologist, neuromuscular blockade was antagonised and the patient was able to maintain normal minute volumes while spontaneously ventilating. With the otolaryngologist present, and with the patient conscious, the trachea was successfully extubated over an airway exchange catheter. A subsequent CT scan revealed an impingement of the trachea by the innominate artery and a mildly ectatic ascending and descending aorta that, in conjunction with tracheomalacia and neuromuscular blockade, could explain the observed signs and symptoms.

Effect of increased body mass index and anaesthetic duration on recovery of protective airway reflexes after sevoflurane vs desflurane.

BACKGROUND: Increased BMI may increase the body's capacity to store potent inhaled anaesthetics, more so with more soluble agents. Accordingly, we asked whether increased BMI and longer anaesthesia prolonged airway reflex recovery. METHODS: We measured time from anaesthetic discontinuation until first response to command (T1); from response to command until ability to swallow (T2); and from anaesthetic discontinuation to recovery of ability to swallow (T3) in 120 patients within three BMI ranges (18-24, 25-29, and >or=30 kg m(-2)). All received sevoflurane or desflurane, delivered via an LMA. RESULTS: T1 and T3 after sevoflurane exceeded T1 and T3 after desflurane: 6.6 (sd 4.2) vs 4.0 (1.9) min (P<0.001), and 14.1 (sd 8.3) vs 6.1 (2.0) min (P<0.0001). T3 correlated more strongly with BMI after sevoflurane (28 s per kg m(-2), P=0.02) than desflurane (7 s per kg m(-2), P=0.03). Regarding T2, patients receiving sevoflurane with BMI >or=30 kg m(-2) were less often able to swallow 2 min after response to command than were those with BMI 18-24 or 25-29 kg m(-2) (3/20 vs 10/20 or 9/20, P<0.05). Each sevoflurane MAC-hour delayed T3 by 4.5 min (268 s) (R=0.46, P<0.001) whereas each desflurane MAC-hour delayed T3 by 0.2 min (16 s) (R=0.10, P=0.44). CONCLUSIONS: Prolonged sevoflurane administration and greater BMI delay airway reflex recovery. The contribution of BMI to this delay is more pronounced after sevoflurane than desflurane.

Droperidol has comparable clinical efficacy against both nausea and vomiting.

BACKGROUND: Droperidol is commonly noted to be more effective at preventing postoperative nausea (PON) than vomiting (POV) and it is assumed to have a short duration of action. This may be relevant for clinical decisions, especially for designing multiple-drug antiemetic regimens. METHODS: We conducted a post hoc analysis of a large multicentre trial. Within this trial, 1734 patients underwent inhalation anaesthesia and were randomly stratified to receive several antiemetic interventions according to a factorial design, one of which was droperidol 1.25 mg vs placebo. We considered differences to be significant when: (i) point estimates of one outcome are not within the limits of the confidence interval (CI) of the other outcome; and (ii) differences in risk ratio (also known as relative risks, RR) are at least 20%. RESULTS: Over 24 h, nausea was reduced from 42.9% in the control to 32.0% in the droperidol group, corresponding to a relative risk (RR) of 0.75 (95% CI from 0.66 to 0.84). Vomiting was reduced from 15.6% to 11.8%, and therefore associated with a similar RR of 0.76 (0.59-0.96). In the early postoperative period (0-2 h), droperidol prevented nausea and vomiting similarly, with an RR of 0.57 (0.46-0.69) for nausea and 0.56 (0.37-0.85) for vomiting. In the late postoperative period (2-24 h), the RR was again similar with 0.83 (0.72-0.96) for nausea compared with 0.89 (0.66-1.18) for vomiting but significantly less compared with the early postoperative period. CONCLUSIONS: We conclude that droperidol prevents PON and POV equally well, yet its duration of action is short-lived.

Ondansetron has similar clinical efficacy against both nausea and vomiting.

Ondansetron is widely believed to prevent postoperative vomiting more effectively than nausea. We analysed data from 5161 patients undergoing general anaesthesia who were randomly stratified to receive a combination of six interventions, one of which was 4 mg ondansetron vs placebo. For the purpose of this study a 20% difference in the relative risks for the two outcomes was considered clinically relevant. Nausea was reduced from 38% (969/2585) in the control to 28% (715/2576) in the ondansetron group, corresponding to a relative risk of 0.74, or a relative risk reduction of 26%. Vomiting was reduced from 17% (441/2585) to 11% (293/2576), corresponding to a relative risk of 0.67, or a relative risk reduction of 33%. The relative risks of 0.67 and 0.74 were clinically similar and the difference between them did not reach statistical significance. We thus conclude that ondansetron prevents postoperative nausea and postoperative vomiting equally well.

Incidence of postoperative nausea and emetic episodes after xenon anaesthesia compared with propofol-based anaesthesia.

BACKGROUND: Xenon has been proved to be safe and efficacious for general anaesthesia in numerous trials. In addition, experimental studies demonstrate that xenon inhibits the 5-hydroxytryptamine type 3 (5-HT(3)) receptor. As 5-HT(3) receptor antagonists are known to decrease postoperative nausea and vomiting (PONV) to an extent comparable with a propofol-based total i.v. technique, we tested the hypothesis that general anaesthesia with xenon would result in a reduced incidence of PONV similar to that observed with propofol-based anaesthesia. METHODS: After obtaining approval from the local ethics committee and written informed consent, 142 patients were randomized to receive xenon anaesthesia or propofol-based total i.v. anaesthesia (TIVA), both supplemented with remifentanil. The incidence of postoperative nausea and emetic episodes was recorded in the post-anaesthesia care unit and on the ward more than 24 h after anaesthesia. RESULTS: A total of 142 patients were equally distributed between the xenon and TIVA groups. Anaesthesia was maintained with mean (sd) concentrations of either xenon 61 (2)% or propofol 100 (20) microg kg(-1) min(-1). Incidences of nausea and emetic episodes over the whole 24-h period were 66.2% and 35.2% in the xenon group and 26.8% and 16.9% in the TIVA group (P<0.001 and P<0.021). CONCLUSION: Despite knowing the 5-HT(3) antagonistic properties of xenon, its use is associated with a higher incidence of nausea and emetic episodes compared with TIVA with propofol.

Remifentanil for general anaesthesia: a systematic review.

We performed a quantitative systematic review of randomised, controlled trials that compared remifentanil to short-acting opioids (fentanyl, alfentanil, or sufentanil) for general anaesthesia. Eighty-five trials were identified and these included a total of 13 057 patients. Intra-operatively, remifentanil was associated with clinical signs of deeper analgesia and anaesthesia, such as fewer responses to noxious stimuli (relative risk 0.65, 95% CI 0.48-0.87), more frequent episodes of bradycardia (1.46, 1.04-2.05), more hypotension (1.68, 1.36-2.07) and less hypertension (0.60, 0.46-0.78). Postoperatively, remifentanil was associated with faster recovery (difference in extubation time of -2.03, 9.5% CI, -2.92 to -1.14 min), more frequent postoperative analgesic requirements (1.36, 1.21-1.53) and fewer respiratory events requiring naloxone (0.25, 0.14-0.47). Remifentanil had no overall impact on postoperative nausea (1.03, 0.97-1.09) or vomiting (1.06, 0.96-1.17), but was associated with twice as much shivering (2.15, 1.73-2.69). Remifentanil does not seem to offer any advantage for lengthy, major interventions, but may be useful for selected patients, e.g. when postoperative respiratory depression is a concern.

[Nausea and vomiting in the postoperative phase. Expert- and evidence-based recommendations for prophylaxis and therapy]. / Ubelkeit und Erbrechen in der postoperativen Phase. Experten- und evidenzbasierte Empfehlungen zu Prophylaxe und Therapie.

There are no consensus guidelines for the management of postoperative nausea and vomiting (PONV) in German speaking countries. This meeting was intended to develop such guidelines on which individual health care facilities can derive their specific standard operating procedures (SOPs). Anesthesiologists reviewed published literature on key topics which were subsequently discussed during two meetings. It was emphasized that recommendations were based on the best available evidence. The clinical relevance of individual risk factors should be viewed with caution since even well proven risk factors, such as the history of PONV, do not allow the identification of patients at risk for PONV with a satisfactory sensitivity or specificity. A more useful approach is the use of simplified risk scores which consider the presence of several risk factors simultaneously. Most individual antiemetic interventions for the prevention of PONV have comparable efficacy with a relative risk reduction of about 30%. This appears to be true for total intravenous anesthesia (TIVA) as well as for dexamethasone and other antiemetics; assuming a sufficiently high, adequate and equipotent dosage which should be weight-adjusted in children. As the relative risk reduction is context independent and similar between the interventions, the absolute risk reduction of prophylactic interventions is mainly dependent on the patient's individual baseline risk. Prophylaxis is thus rarely warranted in patients at low risk, generally needed in patients with a moderate risk and should include a multimodal approach in patients at high risk for PONV. Therapeutic interventions of PONV should be administered promptly using an antiemetic which has not been used before. The group suggests algorithms where prophylactic interventions are mainly dependent on the patient's risk for PONV. These algorithms should provide evidence-based guidelines allowing the development of SOPs/policies which take local circumstances into account.

Patients' willingness to pay for anti-emetic treatment.

BACKGROUND: Post-operative nausea and vomiting (PONV) is a common complication of anaesthesia. This study was conducted in 100 German and 100 Turkish patients scheduled for elective surgery under general anaesthesia to assess the amount patients were willing to pay for an anti-emetic that completely prevented PONV. METHODS: Post-operatively, using Dixon's up and down method, patients completed an interactive computer questionnaire with a random starting point to determine how much of their own money they were willing to pay for a totally effective anti-emetic treatment. RESULTS: On average, participants were willing to pay 65 euro in Germany and 68 euro in Turkey to avoid PONV. However, patients who actually experienced PONV were willing to pay larger amounts: 96 euro in Germany and 99 euro in Turkey. The amount patients were willing to pay was related to female sex, history of motion sickness, non-smoking status and better education. CONCLUSIONS: Despite differences in political and cultural origin, health care system and financial background, the amount patients were willing to pay for an effective anti-emetic was similar in both Germany and Turkey to that reported previously for the USA.