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全麻术后恶心呕吐怎么办?---最新德国处置指南

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全麻术后恶心呕吐怎么办?---最新德国处置指南 M E D I C I N E REVIEW ARTICLE Nausea and Vomiting After Surgery Under General Anesthesia An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment Dirk Rüsch, Leopold H. J. Eberhart, Jan Wallenborn, Peter Kranke SUMMARY Background: The Ge...
全麻术后恶心呕吐怎么办?---最新德国处置指南
M E D I C I N E REVIEW ARTICLE Nausea and Vomiting After Surgery Under General Anesthesia An Evidence-Based Review Concerning Risk Assessment, Prevention, and Treatment Dirk Rüsch, Leopold H. J. Eberhart, Jan Wallenborn, Peter Kranke SUMMARY Background: The German-language recommendations for the management of postoperative nausea and vomiting (PONV) have been revised by an expert committee. Major aspects of this revision are presented here in the form of an evidence-based review article. Methods: The literature was systematically reviewed with the goal of revising the existing recommendations. New evidence-based recommendations for the management of PONV were developed, approved by consensus, and graded according to the scheme of the Scottish Intercol- legiate Guidelines Network (SIGN). Results: The relevant risk factors for PONV include female sex, nonsmoker status, prior history of PONV, motion sick- ness, use of opioids during and after surgery, use of inha- lational anesthetics and nitrous oxide, and the duration of anesthesia. PONV scoring systems provide a rough as- sessment of risk that can serve as the basis for a risk- adapted approach. Risk-adapted prophylaxis, however, has not been shown to provide any greater benefit than fixed (combination) prophylaxis, and PONV risk scores have inherent limitations; thus, fixed prophylaxis may be advantageous. Whichever of these two approaches to manage PONV is chosen, high-risk patients must be given multimodal prophylaxis, involving both the avoidance of known risk factors and the application of multiple vali- dated and effective antiemetic interventions. PONV should be treated as soon as it arises, to minimize patient dis- comfort, the risk of medical complications, and the costs involved. Conclusion: PONV lowers patient satisfaction but is treat- able. The effective, evidence-based measures of prevent- ing and treating it should be implemented in routine prac- tice. ►Cite this as Rüsch D, Eberhart LHJ, Wallenborn J, Kranke P: Nausea and vomiting after surgery under general anesthesia —an evidence-based review concerning risk assessment, prevention, and treatment. Dtsch Arztebl Int 2010; 107(42): 733–41. DOI: 10.3238/arztebl.2010.0733 T he incidence of postoperative nausea and vomit-ing (PONV) after general anesthesia is up to 30% when inhalational anesthetics are used with no prophy- laxis. This makes PONV one of the most common complaints following surgery under general anesthesia, together with postoperative pain (1). As anesthesia is administered approximately 8 mil- lion times per year in Germany for surgery, this means that up to 2.4 million patients suffer from PONV every year (e1) if no prophylaxis is provided. While anesthesia-related mortality and morbidity have fallen dramatically in recent decades, the outcome parameters wellbeing and patient satisfaction are be- coming increasingly important (e2). These are considerably affected by PONV (2–4, e3). Financial issues are also significant, as PONV can lead to a sub- stantial prolongation of time in the recovery room with increased costs of personal care (e4) and in pediatric patients PONV is the most common cause of the approximately 1% to 2% of unplanned hospitalizations following outpatient surgery (e5, e6). Despite their rarity, serious complications caused by PONV which are described in case reports, such as aspiration pneu- monia, Boerhaave’s syndrome, severe subcutaneous emphysema, pneumothorax, rupture of the trachea and loss of vision, provide a warning that this problem is not to be underestimated (e7–e14). In the German-speaking world, recommendations for preventing and treating PONV were first published in 2007. They were based on searches of the literature up to 2005 and therefore require revision due to new findings (5). Although the recommendations of the Society for Ambulatory Anesthesia (SAMBA), also published in 2007, were based on searches of the literature up to 2006, they require a high level of abstraction because of their claim to international validity. For the German- speaking world, this level of abstraction is difficult to translate directly into treatment recommendations (6). This review of PONV prevention and treatment is based on a systematic review of the literature with sub- sequent assessment according to the levels of evidence and grades of recommendations within the framework of expert consensus dating from 2009 (March 30, 2009, Frankfurt am Main, Germany). It can be taken as a Klinik für Anästhesie und Intensivtherapie Universitätsklinikum Gießen und Marburg GmbH: Priv.-Doz. Dr. med. Rüsch, Prof. Dr. med. Eberhart, MA Klinik für Anästhesiolo- gie und Intensivther- apie Universitätsklini- kum Leipzig: Priv.-Doz. Dr. med. Wallenborn Klinik und Poliklinik für Anästhesiologie Uni- versitätsklinikum Würzburg: Univ.-Prof. Dr. med. Kranke, MBA Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41 733 M E D I C I N E basis for incorporation into Standard Operating Pro- cedures (SOPs) in the German-speaking world. Methods The recommendations were developed by an expert committee. All participants had many years’ clinically- oriented scientific experience in the subject. Before beginning the work, relevant key subjects were presented to the participants for their expert opinions. The subjects were researched using Medline, entering search terms related to each subject in combination with established search algorithms for PONV (including “PONV”; “postoperative” AND [“nausea” OR “vomiting” OR “retching”]). They were then presented and discussed at the plenum, taking the available evidence (published up to and including February 2009) into account. State- ments on which agreement had been reached were given a grade of recommendation according to the stipulations of the Scottish Intercollegiate Guidelines Network (SIGN) (Table 1; e15). Where there was disagreement, repeat discussions were held using iterative round emails to the participants (modified Delphi technique). In the event of any further disagreement, the disputes were recorded in the manuscript. PONV risk factors and PONV prognosis systems The pathogenesis of PONV is still largely unclear. However, in recent years it has been possible to identify a number of risk factors for the occurrence of PONV in adults using multivariate methods (1, 7–11, e16–e22). An overview of the risk factors confirmed by several independent studies is provided in Table 2. Results re- garding the effect of the type of operation on the risk of PONV are varied, and discussion of them both at the plenum and in the literature therefore includes conflict- ing opinions (5, 6). As none of the risk factors listed in Table 2 alone is sufficiently able to predict PONV, various prognosis systems have been developed. These have a prediction accuracy rate of approximately 70% (1, 7, 12, e18, e23). Due to the heterogeneous nature of the values of the available scores, and given that the predictive value depends on the decision-making criterion in question (number of risk factors) and the prevalence of the dis- order (PONV), we refer to further reading in the litera- ture for more detailed description (8, 9). Simplified PONV prognosis systems (Table 3) have been shown to have the same prediction ability as more complex PONV prognosis systems (grade B). They are therefore TABLE 1 Levels of evidence and grades of recommendations according to the Scottish Intercollegiate Guidelines Network (SIGN) (e15) Level of evidence 1++ 1 + 1 – 2++ 2 + 2 – 3 4 Requirements High quality meta-analyses, systematic reviews of RCTs, or RCTs with a very low risk of bias Well-conducted meta-analyses, systematic reviews, or RCTs with a low risk of bias Meta-analyses, systematic reviews, or RCTs with a high risk of bias High quality systematic reviews of case control or cohort or studies High quality case control or cohort studies with a very low risk of confounding or bias and a high probability that the relationship is causal Well-conducted case control or cohort studies with a low risk of confounding or bias and a moderate prob- ability that the relationship is causal Case control or cohort studies with a high risk of con- founding or bias and a significant risk that the relation- ship is not causal Non-analytic studies, e.g. case reports, case series Expert opinion Grade of recommendation A B C D Requirements At least one meta-analysis, systematic review, or RCT rated as 1++, and directly applicable to the target population; or A body of evidence consisting principally of studies rated as 1+, directly applicable to the target popu- lation, and demonstrating overall consistency of results A body of evidence including studies rated as 2++, directly applicable to the target population, and demonstrating overall consistency of results; or Extrapolated evidence from studies rated as 1++ or 1+ A body of evidence including studies rated as 2+, directly applicable to the target population and demon- strating overall consistency of results; or Extrapolated evidence from studies rated as 2++ Evidence level 3 or 4; or Extrapolated evidence from studies rated as 2+ 734 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41 M E D I C I N E to be used in preference to more complex systems to as- sess the risk of PONV, as they are more practicable (grade D; e20, e24). PONV prevention An essential part of PONV prevention is the avoidance of confirmed emetogenic factors. Where possible, re- gional anesthesia should be used, as it is associated with a significantly lower risk of PONV in adults than general anesthesia (grade B; [10, e25]). If general anes- thesia is administered, using propofol rather than volatile anesthetics to maintain anesthesia is an effec- tive way of reducing the incidence of PONV (relative risk reduction [RRR] of approximately 19%; grade A; [13, 14]). Not using nitrous oxide is another option for risk reduction (RRR = approximately 12%; grade A; [14, e26]). Avoidance or reduced doses of opioids dur- ing (grade B) and after surgery (grade B) also leads to a lower incidence of PONV (1, 13, e27, e28). To this end, non-opioids and/or regional anesthesia, among other options, can be used. Drug-based PONV prevention Many different substances belonging to different drug groups are available for drug-based PONV prevention. Today most substances are understood to act as antag- onists on specific receptors in the area postrema and on free nerve endings of the vagus nerve. A summary of the most widely-used drugs available in Germany today is provided in Table 4. Adjuvants and non-drug-based PONV prevention According to the results of a recent meta-analysis, in- creased inhaled oxygen concentration has no signifi- cant effect in preventing PONV (grade A; [e46]). This is also true of ginger and ginger extracts (grade A; [e47]). The panel considered the data on the effect of aromatherapy involving isopropyl alcohol in prevent- ing PONV to be insufficient for providing recommen- dations (grade D; [e48]). Studies that have investigated the effect of perioper- ative fluid replacement on the incidence of PONV are too heterogeneous in terms of both different fluid re- placement regimens and results to serve as a valid basis for PONV-prevention recommendations at present (grade D; [e49–e52]). According to the results of a Cochrane Review, stimulation of acupuncture point P6 on the wrist has been shown to be superior to a placebo (e.g. sham acu- puncture) in preventing both nausea (relative risk [RR] 0.72; 95% confidence interval [95% CI] 0.58–0.89) and vomiting (RR 0.71; 95% CI 0.56–0.91) (e53). How- ever, due to study design and its weaknesses regarding treatment blinding, and considerable heterogeneity (e.g. regarding the time of treatment), these conclusions must be interpreted with care (e54). An update of the Cochrane Review on P6 stimulation which included better-designed studies shows again that these treat- ments achieve a significant reduction in nausea (RR 0.71; 95% CI 0.61–0.83) and vomiting (RR 0.7; 95% CI 0.59–0.83) as compared to a placebo, with minimum side effects in adults and children (grade B; [16]), which ultimately led to a positive overall assessment of this method for PONV prevention in adults and children. Nevertheless, P6 stimulation was awarded a SIGN grade B recommendation in the face of continu- ing uncertainty regarding its mechanism of action and data which remain very heterogeneous. Combination prophylaxis and multimodal antiemetic treatment When deciding on PONV prophylaxis, the following key aspects must be considered: ● For dexamethasone, droperidol and ondansetron, a comparable antiemetic efficacy with a relative risk reduction (RRR) for PONV of approximately 26% has been demonstrated (grade A; [14]). ● Total intravenous anesthesia (TIVA) with propo- fol instead of volatile anesthetics and air instead of nitrous oxide has been shown to be comparably effective (RRR 31%) (grade A; [14]). ● The effects of a combination of these antiemetic measures (dexamethasone, droperidol, ondanse- tron and TIVA) are cumulative (grade A; [14]). ● It can be assumed that the results showing a com- parable risk reduction for antiemetic measures and the cumulative nature of the efficacy of anti- emetic treatment (combinations of antiemetics from different classes) are also valid for the other drug-based measures described in Table 4 (grade B). ● There is no evidence to date that a specific anti- emetic is especially effective for a particular pa- tient profile or a particular operation (grade B; [13]). TABLE 2 Risk factors for PONV *1The risk factors listed in each group are ordered according to severity (from most to least severe) Group Patient-dependent Anesthesia-dependent Surgery-dependent General Risk factor*1 Female sex History of PONV Motion sickness Nonsmoker status Volatile anesthetics Duration of anesthesia (risk increases relatively by approx. 60% every 30 min) Nitrous oxide Type of operation Postoperative opioid administration Intraoperative opioid administration Recommendation grade B B B B A B A D A A Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41 735 M E D I C I N E The higher the underlying risk of PONV, the more components from the available antiemetic portfolio are needed to achieve a PONV risk of less than 20% (grade A; [14]). By using a multimodal approach (grade A), it has been possible to achieve a dramatic re- duction in the incidence of PONV (less than 10%) and an increase in patient satisfaction, even for high-risk patients with an underlying PONV risk of more than 80% (2, e55). PONV treatment When PONV occurs, prompt treatment is indicated, as the likelihood of PONV to persist or to recur is at least 65% (grade A; [11, 17]). Only 5HT3 receptor antagonists have been fully re- searched for PONV treatment and confirmed as being effective (grade A; [18]). They are, therefore, first-line drugs for treatment of PONV, especially when no prophylaxis has been administered beforehand (grade D). The data available on all the other drug- based and non-drug-based methods described above is less extensive, although dexamethasone (grade A), ha- loperidol (grade A), dimenhydrinate (grade B) and promethazine (grade C) have been shown to be effec- tive in treating PONV (19, e56, e57). As those interventions that have proven to be effec- tive (grade A) for treatment of PONV have also been shown to be similarly effective (grade A) for prophy- laxis of PONV, there is consensus that the reverse is also true: All interventions for which it has been pos - sible to demonstrate the highest level (grade A) of vali- dated efficacy in preventing PONV, efficacy in treating PONV can also be assumed, and these measures can therefore also be recommended as treatment (grade B). Drug-based measures associated with slow onset of effect (e.g. dexamethasone, scopolamine) should not be used as monotherapy, but only in combination with a fast-acting substance as part of treatment (grade D). For reasons of practicability, the same doses as those used for prevention are also recommended for treat- ment (grade D), even though for some substances (e.g. ondansetron) it has been shown that lower doses are also effective for treatment (18). If PONV occurs despite prophylaxis, the primary recommendation (particularly in the immediate post - operative phase) is to administer a substance from another drug group (grade A; [20, e56, e57]). In PONV treatment, combination therapy should be considered, as despite treatment the recurrence rate of PONV over the subsequent 24 hours is 35% to 50%, and the combination of dexamethasone plus dolasetron or haloperidol has already been shown to be superior to monotherapy (grade A; [17–19]). A comparable effec- tiveness as part of combination therapy can also be assumed for other combinations of established anti - emetics (grade D). PONV in children The incidence of PONV is strongly age-dependent. While children under 3 years of age are rarely affected, TABLE 3 Validated, simplified PONV prognosis systems for adults and children, stating the risk factors involved and calculated incidences of PONV Prognosis system Patient population Risk factors Calculated incidence of PONV with n risk factors present (sum of the risk factors listed above) n 0 1 2 3 4 5 Koivuranta et al. (7) Adults Female sex Prior history of PONV Prior history of motion sickness Nonsmoker status Length of operation >60 min % 17 18 42 54 74 87 Apfel et al. (1) Adults Female sex History of PONV History of motion sickness Nonsmoker status Expected postoperative administration of opioids % 10 21 39 61 79 Not stated Eberhart et al. (12) Children Age >3 years History of PONV or motion sickness in the child or a first- degree relative Strabismus surgery Length of operation >30 min % 9 10 30 55 70 Not stated 736 Deutsches Ärzteblatt International | Dtsch Arztebl Int 2010; 107(42): 733–41 M E D I C I N E TABLE 4 Overview of available antiemetics with well-researched efficacy in preventing PONV The receptors stated in brackets in the second column are the receptors on which the drug groups indicated in the first line have antiemetic effects. Doses stated are for intravenous administration (except for aprepitant). Side effects listed are the symptoms frequently reported in PONV studies. Level and grade of recommendations according to SIGN criteria; AE: adverse effect; CI: contraindication; BG: blood glucose; ECG: electrocardiogram; IV: intravenous. Active substance Dexametha- sone Granisetron Ondansetron Palonosetron Tropisetron Droperidol Haloperidol Metoclopramide Dimenhydrinate Scopolamine Aprepitant Substance g roup Corticosteroids Serotonin antag- onists (5-HT3 re- ceptors) Dopamine antag- onists: butyrophe- none (D2 recep- tors) Dopamine antag- onists: benzamide (D2 receptors) Histamine antag- onists (H1 recep- tors) Anticholinergics (muscarinergic acetylcholine receptors) Neurokinin antag- onists (NK1 recep- tors) Dose for adults 4–8 mg 1 mg 4 mg 0.075 mg 2 mg 0.625–1.25 mg 1–2 mg 25–50 mg 62 mg 1 mg/24 hrs 40 mg (avail- able only as 80 and 125 mg capsules in Germany) Dose for children 0.1–0.15 mg 0.02 mg/kg 0.1 mg/kg No data 0.1 mg/kg 0.01–0.015 mg/kg No data 0.15 mg/kg 0.5 mg/kg No data No data Recommen- dation grade (literature) A (14, 15, e29 –e31) A (14, 15, e33 –e36) A (14, 15, e33, e38) A (e39, e40) A (11, 15) A (13, e42) A (e43) A
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