Postoperative nausea and vomiting: Physiopathology, risk factors, prophylaxis and treatment | Revista Española de Anestesiología y Reanimación (English Edition)

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Sousa, C. Pinho, A. Santos, F.J. Abelha" "autores" => array:4 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Sousa" ] 1 => array:2 [ "nombre" => "C." "apellidos" => "Pinho" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "Santos" ] 3 => array:2 [ "nombre" => "F.J." 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Veiga-Gil, J. Pueyo, L. López-Olaondo" "autores" => array:3 [ 0 => array:4 [ "nombre" => "L." "apellidos" => "Veiga-Gil" "email" => array:1 [ 0 => "noraveigagil@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "J." "apellidos" => "Pueyo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "L." "apellidos" => "López-Olaondo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Anestesiología, Reanimación y Terapia del Dolor, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Anestesiología y Cuidados Intensivos, Clínica Universidad de Navarra, Pamplona, Navarra, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Náuseas y vómitos postoperatorios: fisiopatología, factores de riesgo, profilaxis y tratamiento" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2269 "Ancho" => 3067 "Tamanyo" => 438904 ] ] "descripcion" => array:1 [ "en" => "Pathophysiology retching/vomiting. AP: area postrema; CPG: central pattern generator; CVM: caudal ventrolateral medulla; RVM: rostral ventrolateral medulla; NTS: nucleus tractus solitarius; DNV: dorsal nucleus of the vagus; Vest N.: vestibular nuclei." ] ] ] "textoCompleto" => "IntroductionSince the 1990s, many scientific articles dealing with postoperative nausea and vomiting (PONV) have been published, yet many authors remark on the scant progress made in this field in the past 20 years. Nevertheless, the research carried out has raised awareness of the problem and led to the development of prognostic scales, protocols, and even automatic systems for flagging high-risk patients based on their medical history. Now, for the first time in Spain, a group of experts from the Spanish Society of Anaesthesiology published a suite of “recommendations for the prevention and treatment of PONV”.<a class="elsevierStyleCrossRef" href="#bib0255">1</a> It is important to bear in mind that new antiemetic drugs with better safety profiles are emerging, and studies in the near future may determine their usefulness in controlling PONV. Interestingly, when talking to our patients we often find that many report severe PONV after their first anaesthetic experience, but not in recent surgeries.This shows that progress is being made in preventing PONV. So, what is the problem today? Firstly, in the control of high-risk patients and highly emetogenic surgeries or procedures in which retching or vomiting may cause serious complications; we simply cannot allow certain patients to experience PONV. Incidence of PONV in the general surgical population is around 25%–30%, and can increase to as much as 80% in high-risk populations if they do not receive prophylaxis.<a class="elsevierStyleCrossRef" href="#bib0260">2</a> The incidence in high-risk patients remains considerable (60%), and affects their recovery insofar as it interferes with sleep and the start of the intake.<a class="elsevierStyleCrossRef" href="#bib0265">3</a> “Clinically relevant” PONV (3 or more emetic episodes, or severe or long-term nausea) is associated with more complications and poorer postoperative recovery.<a class="elsevierStyleCrossRef" href="#bib0270">4</a> Secondly, there is the problem of late-onset PONV or post-discharge nausea and vomiting (PDNV) after outpatient surgery, which has an incidence of about 45% on the first day and up 6% on day 7<a class="elsevierStyleCrossRefs" href="#bib0275">5,6</a> and is particularly hard to manage. Risk factors and existing prognostic scales are not applicable to PDNV/late-onset PONV, and in these cases many antiemetics seem ineffective in the long term.<a class="elsevierStyleCrossRef" href="#bib0280">6</a> Thirdly, our specialty is particularly affected by decisions made by pharmaceutical companies and drug agencies, as in the case of droperidol. In addition, some drugs used as antiemetics (neuroleptics, antihistamines, corticosteroids, etc.) were initially developed for other purposes but later found to be effective in this indication. As such, their antiemetic action is rarely included in the technical specifications of the product, and this greatly complicates clinical research. However, the most important problem today is how to translate the enormous amount of scientific evidence into practical benefit for outpatients. Clinical guidelines are notoriously hard to implement. This and other situations have led to the current dilemma: general multimodal vs scheduled risk-adopted prophylaxis based on prognostic scales.<a class="elsevierStyleCrossRef" href="#bib0285">7</a> Our aim has been to summarise and organise the scientific evidence for PONV in order to contribute to our understanding of this problem in our setting, and to bring us closer to the goal of “PONV-free” hospitals.Pathophysiology of PONVThe pathophysiology of nausea and vomiting is complex and not fully understood. The first difficulty lies in the different pathophysiology of nausea with respect to vomiting. In the case of nausea, our knowledge is very limited. We know that nausea is a conscious sensation involving cortical structures, while vomiting is a complex reflex controlled by the medulla oblongata. The act of vomiting involves a combination of emetic afferents and the coordinated action of respiratory, gastrointestinal and abdominal muscles involved in the act of vomiting/retching. This entire process is controlled by what was formerly known as the vomiting centre. The current hypothesis points to the existence of an organised group of neurons located in the medulla oblongata that are activated sequentially by the central pattern generator, which coordinates the sequence of behaviours during emesis. For vomiting to occur, these neurons must be activated in the proper sequence, which is why the notion of a “central pattern generator” is more acceptable than a “vomiting centre”.<a class="elsevierStyleCrossRef" href="#bib0290">8</a> Although the main neuronal groups that stimulate the central pattern generator are not well defined, the nucleus tractus solitarius (NTS) and other specific nuclei of the reticular formation (including respiratory nuclei) are believed to be important sites for generating emesis.<a class="elsevierStyleCrossRef" href="#bib0295">9</a> The NTS activates the central pattern generator and the surrounding neuronal groups that trigger the autonomic and motor response of vomiting (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Four pathways activate vomiting by direct projections to the NTS: (1) gastrointestinal tract (GIT) vagal afferent fibres, (2) the vestibular system, (3) the cerebral cortex, thalamus and hypothalamus, and (4) the area postrema (AP). Vagal afferent fibres of the GIT are excited by serotonin (5-HT) released from enteroendocrine cells when they detect circulating drugs or local toxins in the GI tract. Vestibular nuclei receive motion-related sensory input. Activation of the cerebral cortex and areas of the thalamus and hypothalamus trigger psychogenic-related vomiting and vomiting secondary to visual or olfactory stimuli.Research has gradually confirmed the importance of the AP and its chemoreceptor trigger zone. The AP is a richly vascularised medullary structure located at the base of the fourth ventricle, which lacks a specific blood–brain barrier. Because of these characteristics, its chemoreceptors are sensitive to emetogenic agents in the blood and the cerebrospinal fluid, and it therefore plays a key role in drug-induced emesis. Information from emetic afferents is transmitted to the AP via various pathways: (1) direct visceral afferents via the vagus nerve, (2) blood flow, and (3) autonomic stimuli from descending pathways from the hypothalamus.Ultimately, afferents activate the vagus nerve and neuronal groups associated with nausea and vomiting through various neurotransmitters. Five such neurotransmitters have been identified so far: 5-HT, dopamine (D), histamine (H), substance P, acetylcholine and opioids. Their corresponding receptors are located in vagal afferents (5-HT3 receptors), the vestibular nucleus (M3/M5 muscarinic acetylcholine receptors and H1 receptors), the AP (μ-, 5-HT3- and D2-opioid receptors) and the NTS (μ receptors, 5-HT3, neurokinin-1 [NK-1], and the substance P receptor).Risk factors, prognostic scales and pattern of occurrenceDue to the multifactorial origin of PONV, any potential risk factor must be weighed up against other possible co-existing risk factors in order to avoid analytical errors. The first articles studying multiple risk factors using logistic regression models date from the 1990s. Until then, researchers had focused on the study of risk factors in isolation, without the influence of other variables. This meant that the real effect of the factor was uncertain, and led to flawed beliefs.The most important limitation in the study of risk factors is the difficulty in differentiating between PONV risk factors and confounders. A limited understanding of the pathophysiology can easily lead to confusion between cause and association: is gynaecological surgery an independent risk factor for PONV? Or is it a confounding factor, and the real risk factor is female sex? Is the use of opioids an independent risk factor? Or is it the pain associated with certain types of surgeries that causes PONV and higher opioid requirements? In 2012, using all the scientific evidence available at that time, Apfel et al.<a class="elsevierStyleCrossRef" href="#bib0300">10</a> published a meta-analysis of PONV risk factors to show which are independent predictors and which are not. Among all the risk factors put forward at that time, sufficient evidence was only available to confirm the following as independent predictors of PONV:For postoperative nausea/PONV:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">•Patient-specific predictors: Female gender (odds ratio [OR] 2.57), history of PONV/motion sickness (OR 2.09), non-smoking status (OR 1.82), history of motion sickness (OR 1.77) and age (OR 0.88 per decade).</li><li class="elsevierStyleListItem" id="lsti0010">•Anaesthesia-related predictors: use of volatile anaesthetics (OR 1.82), duration of anaesthesia (OR 1.46 per hour), use of nitrous oxide (OR 1.45) and postoperative use of opioids (OR 1.39).</li><li class="elsevierStyleListItem" id="lsti0015">•Surgery-related predictors: cholecystectomy (OR 1.90), laparoscopic procedures (OR 1.37) and gynaecological surgery (OR 1.24).</li></ul>For postoperative vomiting: predictors were similar to those of postoperative nausea/PONV, particularly: female gender (OR 2.73), history of PONV/motion sickness (OR 2.32), non-smoking status (OR 1.78). In the case of postoperative vomiting, neither age nor any of the types of surgery analysed were significant enough to warrant consideration as a predictor.Clinical guidelines published in 2014 confirmed the risk factors discussed so far, and added age <50 and general anaesthesia (incidence of PONV 9 times greater than in regional anaesthesia<a class="elsevierStyleCrossRef" href="#bib0260">2</a>). The latest evidence shows that nitrous oxide has a time-dependent emetic effect, with the risk of PONV increasing by 20% per hour from the first 45min of exposure.<a class="elsevierStyleCrossRef" href="#bib0305">11</a>Much progress has been made recently in the study of genetic predisposition and PONV. A familial pattern of PONV and antiemetic resistance has been observed that seems to be due to polymorphisms in the genes encoding some receptors, such as A and B subunits of the 5-HT receptor (5-HT3A and 5-HT3B), M3 muscarinic receptors and the NK-1 receptor. Other recently confirmed risk factors are chemotherapy-induced nausea and vomiting (CINV). A history of CINV is a predictor of PONV, and a 2015 study showed that cancer patients with a history of CINV were more likely to present PONV when undergoing surgery.<a class="elsevierStyleCrossRef" href="#bib0310">12</a>Risk factors for PONV, PDNV, and late-onset PONV are not exactly the same. Studies published by Apfel et al.<a class="elsevierStyleCrossRef" href="#bib0280">6</a> and Odom-Forren et al.<a class="elsevierStyleCrossRef" href="#bib0275">5</a> have contributed to our understanding of the risk factors of PONV (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>). We also know that the causes of PONV in the first 48 postoperative hours and PONV at 3 days are different. To date, the following risk factors have been shown to be independent predictors for NVPA<a class="elsevierStyleCrossRef" href="#bib0280">6</a>: female gender, age under 50 years, history of PONV, use of opioids in the postanaesthesia care unit (PACU), and nausea in the PACU. Pain is the most important risk factor associated with late-onset PONV, occurring between days 3 and 7 after major outpatient surgery (MOS). It is important to note that neither the type of surgery nor non-smoking status are independent predictors of PONV. Patients presenting nausea in the PACU have a three-fold risk of PONV. It should also be noted that the use of intraoperative ondansetron decreases the incidence of PONV in the PACU but not after discharge, and the opposite occurs with corticosteroids, which do not seem to have a protective effect in the PACU, but do protect against PDNV. Total intravenous anaesthesia has an antiemetic effect only during the first postoperative hours, and therefore should not replace the administration of antiemetics in MOS patients.<a class="elsevierStyleCrossRefs" href="#bib0280">6,13</a><elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Menstrual cycle, mask ventilation and the expertise of the anaesthetist, use of neostigmine, BMI, anxiety, fraction of inspired oxygen, use of a nasogastric tube, American Society of Anesthesiologists (ASA) physical status score, preoperative fasting and migraines have all been ruled out as risk factors.<a class="elsevierStyleCrossRefs" href="#bib0260">2,10</a>Risk factors are used to create prognostic scales, which allow clinicians to classify patients according to their risk of PONV and to decide whether to prevent or treat the condition, and how. One such scale, the simplified Apfel scale (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>) was developed in the 1990s. This scale proved to be as effective as its predecessors, but because it is simplified and weighs each risk factor equally, it is easily applied and is currently the most widely used tool.<a class="elsevierStyleCrossRef" href="#bib0320">14</a> It is important to bear in mind that these prognostic scales were designed and validated in adults undergoing surgery under balanced general anaesthesia, and are therefore only valid in similar situations.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The Eberhart scale is used in paediatric patients, with the recent addition of the Bourdaud scale, which has a high predictive value but is awaiting external validation.<a class="elsevierStyleCrossRef" href="#bib0325">15</a>As discussed, neither risk factors nor conventional prognostic scales have been shown to be predictive of PDNV. In 2012, Apfel et al.<a class="elsevierStyleCrossRef" href="#bib0280">6</a> published a prognostic scale for PDNV based on the following factors: female gender, age <50 years, history of PONV, use of opioids in the PACU and nausea in the PACU (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).It is not only important to predict the risk of PONV, but also to predict when it will occur. The widespread notion that PONV is a complication in the immediate postoperative period is unfounded. PONV can onset at any time during the first 72 postoperative hours. In hospitalised patients, incidence peaks at between 2 and 12h after surgery, and it is therefore a complication that occurs most often in the hospital ward and not in the PACU, as previously believed.<a class="elsevierStyleCrossRef" href="#bib0330">16</a> PDNV has been described in MOS patients up to 7 days post surgery, and a key factor seems to be the ride home from the hospital, with incidence peaking during this trip and on arrival home on the day of surgery.<a class="elsevierStyleCrossRef" href="#bib0275">5</a>Prevention and treatmentThere are currently various schools of thought in respect of PONV prophylaxis: general multimodal vs scheduled risk-adopted prophylaxis.<a class="elsevierStyleCrossRef" href="#bib0335">17</a> According to clinical guidelines, the safest and most cost-effective approach is scheduled risk-adapted prophylaxis based on prognostic scales,<a class="elsevierStyleCrossRef" href="#bib0255">1</a> but this seems to have done little to reduce the current incidence of PONV (20%–30%), especially in high-risk patients. Matters are further aggravated by poor adherence to the recommendations of clinical guidelines in daily practice, and the modest predictive power of prognostic scales.<a class="elsevierStyleCrossRef" href="#bib0285">7</a> To overcome this, some authors, citing the low cost of current antiemetic agents and their excellent safety profile, defend the general multimodal prophylaxis approach.<a class="elsevierStyleCrossRef" href="#bib0340">18</a> Others propose an intermediate, and probably more sensible, solution: apply predictive models along with a therapeutic recommendation for the type of prophylaxis to be administered. This would increase the number of antiemetics administered and decrease the incidence of PONV, especially in high-risk patients. This, together with lowering the risk threshold for prophylaxis administration, would reduce the current incidence of PONV.<a class="elsevierStyleCrossRef" href="#bib0345">19</a>The following is a summary of the recommendations of the ASA<a class="elsevierStyleCrossRef" href="#bib0260">2</a> and the Spanish Society of Anesthesiology,<a class="elsevierStyleCrossRef" href="#bib0255">1</a> slightly adapted to make them applicable to cases of MOS patients and procedures in which vomiting or retching increases the risk of complications.Step 1: Identify the patient's risk for PONV by applying the Apfel prognostic scale. Prophylaxis should be administered in sufficiently high-risk patients. A more liberal use of prophylaxis is warranted in outpatient surgery and in patients in whom vomiting or retching would lead to considerable clinical risk (mandibular sutures following maxillofacial surgery, risk of bleeding due to retching-induced increase in intracranial pressure following neurosurgery, or eosophagogastric surgery).Step 2: reduce the baseline risk by applying general strategies. The following are the recommendations given in the latest clinical guidelines with their level of evidence (evidence grading system used by the ASA in previous clinical guidelines for perioperative pain and PONV)<a class="elsevierStyleCrossRef" href="#bib0260">2</a>:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020">•Choose regional anaesthesia over general anaesthesia (A1).</li><li class="elsevierStyleListItem" id="lsti0025">•Use propofol for TIVA induction and maintenance (A1). Propofol is associated with a lower incidence of PONV in the first 6 postoperative hours.</li><li class="elsevierStyleListItem" id="lsti0030">•Avoid the use of nitrous oxide (A1) and volatile anaesthetics (A2).</li><li class="elsevierStyleListItem" id="lsti0035">•Minimise the use of intraoperative opioids (A2) and postoperative opioids (A1).</li><li class="elsevierStyleListItem" id="lsti0040">•Adequate hydration (A1). Administration of IV fluids at 30mL/kg in surgeries associated with blood loss reduces the overall incidence of PONV, irrespective of the type of fluid used.</li></ul>Step 3: administer prophylaxis in proportion to the calculated risk, as shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Step 4: treat PONV if it appears, and assess the need for antiemetic prophylaxis or treatment at discharge in MOS patients. Although several studies have been published with different combinations of antiemetics for PDNV prophylaxis, these are not evidence-based, and some of the antiemetics studied are not available in Spain. It is important to note that PONV and/or requirement of opioids in the PACU are risk factors for PDNV, and one of the antiemetics studied that may be used in Spain is 8mg oral ondansetron immediately before discharge and in the morning of the first and second postoperative day, in addition to daily telephone follow-up.<a class="elsevierStyleCrossRefs" href="#bib0260">2,20</a>Pharmacological strategiesSeveral studies have shown the efficacy of antiemetic combinations vs monotherapy. The combination of antiemetics with different mechanism of action has a cumulative effect in reducing the appearance of PONV, and each administration reduces incidence by 25%–30%.<a class="elsevierStyleCrossRef" href="#bib0355">21</a>Serotonin receptor antagonists (5-HT3) or setronsThese block the action of 5-HT receptors in the AP, NTS and GIT vagal afferents. Drugs in this group includes: ondansetron, granisetron, dolasetron, tropisetron, ramosetron and palonosetron. Ondansetron is the most widely studied and the “gold standard” compared with other antiemetics, as it has proven to be the most cost-effective of all (evidence level A1). It is recommended at an IV dose of 4mg at the end of surgery, and has a half-life of 4h. It is usually considered more effective against vomiting than nausea, although the evidence is inconsistent. It has a number needed to treat (NNT) of approximately 6 for prevention of vomiting and 7 for prevention of nausea.<a class="elsevierStyleCrossRef" href="#bib0360">22</a> The most common adverse reactions are headache (number needed to harm [NNH] 36), subclinical elevation of hepatic enzymes (NNH 31) and constipation (NNH 23). Setrons (except palonosetron) have been shown in vitro to block sodium channels and can prolong the QT interval. In clinical practice, ondansetron, tropisetron and granisetron can have the dose-dependent effect of prolonging the QT interval and decreasing heart rate, although there is a growing body of evidence to show that QT prolongation is minor and of little clinical consequence.<a class="elsevierStyleCrossRef" href="#bib0365">23</a> The use of 5-HT antagonists in combination with dexamethasone or droperidol has also been shown to be as safe as monotherapy.<a class="elsevierStyleCrossRef" href="#bib0370">24</a>Palonosetron at an IV dose of 0.075mg is effective, well tolerated, and approved by the Food and Drug Administration (FDA). Compared with ondansetron 8mg, it proved more effective in the prophylaxis of PONV at 24 and 72h, with a lower incidence of headache and less need for rescue antiemetics.<a class="elsevierStyleCrossRef" href="#bib0375">25</a> In Spain, it is only approved for PONV. Recent interest in palonosetron stems from the fact that it does not prolong the QT interval, has a longer half-life (40h), and binds to the 5-HT receptor in such a way as to cause conformational changes.<a class="elsevierStyleCrossRef" href="#bib0380">26</a> Because of this, some authors recommend it as one of the options for PONV prophylaxis.<a class="elsevierStyleCrossRef" href="#bib0385">27</a>CorticoidsDexamethasone has proven effective as an antiemetic in multiple clinical trials.<a class="elsevierStyleCrossRef" href="#bib0390">28</a> It is usually administered at an IV dose of 8mg (NNT=4), but following the multicentre IMPACT study and systematic reviews,<a class="elsevierStyleCrossRef" href="#bib0355">21</a> some guidelines recommend 4–5mg (evidence level A1). A recent meta-analysis has shown that in terms of antiemetic efficacy, 4–5mg is as effective as 8–10mg, although dexamethasone 8mg improves the quality of postoperative recovery.<a class="elsevierStyleCrossRef" href="#bib0395">29</a> The dose in children is 0.15mg/kg (up to 5mg). Its antiemetic mechanism of action is not entirely understood, but several theories have been put forward, including: inhibition of arachidonic acid and prostaglandins, inhibition of 5-HT release in the GIT, reduction of 5-HT precursor expression in the central nervous system, changes in blood–brain barrier permeability to serum proteins, release of endorphins, or boosting the effect of other antiemetics by enhancing the sensitivity of 5-HT receptors and acting directly on the NTS by activating glucocorticoid receptors. Despite these differences, there is widespread consensus that it must be administered during anaesthesia induction, due to its slow onset of action (2h). It has a prolonged effect (72h), and no adverse effects have been reported. The only relative contraindication for dexamethasone is administration in diabetic or obese patients.<a class="elsevierStyleCrossRef" href="#bib0260">2</a> In terms of secondary hyperglycaemia, evidence suggests that blood glucose increase is similar in type 2 diabetics and nondiabetics, and is mainly due to surgical stress.<a class="elsevierStyleCrossRef" href="#bib0400">30</a> Neither has dexamethasone use been associated with increased surgical wound infection or major bleeding. IV administration cause perineal pruritus. Because of its duration of action and safety profile, it is highly recommended in MOS patients. Methylprednisolone has also been shown to be an effective anti-emetic in IV doses of 40mg.<a class="elsevierStyleCrossRef" href="#bib0405">31</a>Dopamine antagonistsDroperidol blocks the action of D2 receptors in the AP. The recommended IV dose is 0.625–1.25mg, and it has an NNT of 5 (evidence level A1), although a recent meta-analysis shows that low doses (≤1mg) are effective.<a class="elsevierStyleCrossRef" href="#bib0410">32</a> It should be administered at the end of surgery. Droperidol has a half-life of 2–3h. Following an FDA warning in 2001 on the risk of arrhythmias, droperidol was withdrawn from hospitals in Spain. In 2009, it was re-introduced for the prevention and treatment of PONV and morphine-related nausea and vomiting (NNT=3). According to the FDA, electrocardiographic monitoring is required for 2–3h after administration. The effect of droperidol on the QT does not increase when administered in combination with ondansetron.<a class="elsevierStyleCrossRef" href="#bib0415">33</a> If it were not for the FDA alert, ASA clinical guidelines would recommend droperidol as a first line antiemetic in PONV prophylaxis. The Spanish Society of Anaesthesiology guidelines, however, do recommend it as a first-line drug, with ondansetron as a rescue remedy. Evidence has shown that current prophylactic doses are not associated with severe cardiac events.<a class="elsevierStyleCrossRef" href="#bib0420">34</a>Droperidol is the most widely recommended drug for opioid-induced PONV, and it is the only drug with this indication in Spain. Guidelines recommend adding droperidol to intravenous patient-controlled analgesia, at a dose of 0.1mg per milligram morphine, with a maximum of 4mg of droperidol daily, although the minimum effective dose has yet to be confirmed. These doses reduce both incidence of PONV and morphine requirements.<a class="elsevierStyleCrossRef" href="#bib0425">35</a>Low-dose (0.5–2mg IV or IM) haloperidol is recommended as an antiemetic, with an NNT of 4 and 6 for nausea and vomiting, respectively. Its effectiveness is comparable to that of ondansetron or droperidol.<a class="elsevierStyleCrossRef" href="#bib0430">36</a> It has a longer half-life than droperidol (16h), but is less specific for the D2 receptor and there is no evidence for the best timing of administration and the lowest effective dose, as some studies have shown limited effectiveness for low-dose haloperidol.<a class="elsevierStyleCrossRef" href="#bib0330">16</a> It is also associated with QT prolongation, although evidence shows that it is safe at low doses.<a class="elsevierStyleCrossRef" href="#bib0435">37</a> The incidence of adverse reactions to neuroleptics is dose-proportional. Droperidol is as well tolerated as setrons, but provides more sedation (in a dose dependent manner). Administration of neuroleptics at higher than recommended doses can cause anxiety, restlessness, extrapyramidal symptoms and even neuroleptic malignant syndrome.Muscarinic cholinergic antagonistsInterest in the transdermal scopolamine patch, originally designed to treat motion sickness, has recently been rekindled. Because of its low onset of action (2–4h), the patch (1.5mg) is applied 4h before surgery, providing sustained release for 72h. Theoretically, it causes a high incidence of cholinergic adverse events (dry mouth, blurred vision, agitation, dysphoria, dizziness, confusion, etc.), although the latest studies suggest a far lower incidence.<a class="elsevierStyleCrossRef" href="#bib0440">38</a> Adverse reactions may be more common in children and the elderly.H1 antihistimines: dexclorfeniramina, dimenhydrinate, diphenhydramine, cyclizine, meclizineThese drugs are less common due to their sedative effect. They have shown efficacy in some studies, but have not been widely studied as other antiemetics.<a class="elsevierStyleCrossRef" href="#bib0445">39</a> According to the latest guidelines, they are not considered first-line drugs in the prophylaxis of PONV.<a class="elsevierStyleCrossRef" href="#bib0260">2</a> The most common adverse reactions are dry mouth, blurred vision, sedation, and urinary retention.Neurokinin receptor antagonists: aprepitant, casopitant, rolapitant, fosaprepitant and vestipitantSubstance P is a neuropeptide involved in the pathophysiology of nausea and vomiting because it binds to NK-1 receptors in the central and peripheral nervous system. These drugs competitively inhibit the action of substance P and act both centrally (by blocking neurotransmission in the NTS) and peripherally (by blocking NK1 receptors located on vagal terminals in the gut) to decrease the intensity of the emetic afferent message and prevent nausea and vomiting.<a class="elsevierStyleCrossRef" href="#bib0450">40</a> The only FDA-approved drug in this group for PONV is aprepitant. Aprepitant has a half-life of 40h, and the recommended prophylaxis dose is 40mg po 1–3h before surgery. These drugs are well tolerated and do not cause sedation or QT prolongation. Aprepitant is comparable to ondansetron in efficacy, and is more effective in reducing nausea severity in the first 48h, and in preventing vomiting at 24 and 48h postoperatively.<a class="elsevierStyleCrossRef" href="#bib0450">40</a> NK1 inhibitors may be an attractive option for controlling late-onset PONV/PDNV, and in patients that have not responded to other antiemetics.<a class="elsevierStyleCrossRef" href="#bib0385">27</a> The only NK1 inhibitor available in Spain is aprepitant, at a recommended dose of 80 and 125mg for CINV.Non-pharmacological strategiesNon-pharmacological PONV management strategies include acupuncture, electroacupuncture, acupressure, transcutaneous electrical stimulation, and hypnosis.<a class="elsevierStyleCrossRef" href="#bib0455">41</a> Several studies have evaluated the efficacy of P6 point stimulation in preventing PONV, but results are inconclusive. Some authors report a reduction in incidence and intensity of PONV during the first 6 postoperative hours compared with placebo, and it has been shown to be as effective as any of the most widely used antiemetics.<a class="elsevierStyleCrossRef" href="#bib0460">42</a> Although easy to implement, the reason these measures are not used in clinical practice could be that we are unfamiliar with such techniques, the recommendations for their use are unclear, there is insufficient evidence, and because drugs are so much easier to administer. However, since they have proved effective in some cases, they should be included in the multimodal approach to PONV.<a class="elsevierStyleCrossRef" href="#bib0465">43</a>Strategies proven to be ineffective, without sufficient evidence or that need further investigationThere are basically 3 drugs that should be discussed in this context: metoclopramide, midazolam and gabapentin. Although commonly used as an antiemetic, evidence shows that IV metoclopramide 10mg is not effective for prophylaxis of PONV because the dose used is too low, and higher doses increase the risk of side effects, particularly extrapyramidal symptoms.<a class="elsevierStyleCrossRef" href="#bib0470">44</a> Midazolam and gabapentin warrant special mention, as they have hitherto been included in the “insufficient evidence” group. However, recent meta-analyses and clinical trials have shown that preoperative oral gabapentin 600mg and preoperative IV midazolam 2–5mg are effective in the prophylaxis of PONV.<a class="elsevierStyleCrossRefs" href="#bib0475">45,46</a>Treatment of PONVRecurrence after a first, untreated, episode of PONV can be as high as 84%.<a class="elsevierStyleCrossRef" href="#bib0485">47</a> Therefore, aggressive measures must be taken if prophylaxis fails and the patient presents PONV. Generally speaking, the same drugs as used for PONV prophylaxis can be used in treatment; combinations can also be used. It is important to choose the antiemetic rescue remedy in accordance with the prophylaxis administered, in other words, the drug used as first-line rescue must belong to a different class of medicines as that used for prophylaxis if it is administered less than 6h after the prophylaxis. The only exceptions to this rule are dexamethasone, scopolamine patches, aprepitant and palonosetron, which, because of their long half-life, should not be repeated. If antiemetic prophylaxis was not administered, PONV should be treated with low-dose 5-HT3 antagonists, the most widely studied of these being IV ondansetron at a therapeutic dose of 1mg.<a class="elsevierStyleCrossRef" href="#bib0490">48</a> IV droperidol at doses ranging from 0.625 to 1.25mg is also effective. There are insufficient data on dexamethasone. Its efficacy as first-line treatment of PONV is questionable because of its slow onset of action, but it could be useful in combination with other antiemitics.<a class="elsevierStyleCrossRef" href="#bib0390">28</a> Low-dose IV propofol (10mg) seems to be effective, although it has a shorter duration of action than the more widely used antiemetics.<a class="elsevierStyleCrossRef" href="#bib0260">2</a> A less common approach, but one that could be considered in some cases, is to change to another 5-HT3 antagonist. Because setrons are metabolised by different isoenzymes, some patients that do not respond to ondansetron may respond to granisetron.<a class="elsevierStyleCrossRef" href="#bib0495">49</a>Although IV midazolam (2–5mg) does not seem to have taken its place in the PONV toolbox, there is both evidence and clinical experience to support its efficacy,<a class="elsevierStyleCrossRef" href="#bib0500">50</a> above all in patients with intense nausea that does not respond to conventional antiemetics. Neither should we forget the antiemetic properties of antihistamines, such as dexclorfeniramina, despite a high incidence of adverse effects, such as somnolence.Conclusions and recommendationsPONV is not life-threatening, but it is nevertheless common and difficult to control, especially in high-risk and MOS patients. New generation, long-acting antiemetics (aprepitant, palonosetron or scopolamine patches) recommended for the management of late-onset PONV/PDNV, particularly the latest additions, are not available in Spain. The future availability of these drugs will be decided by the pharmaceutical industry. Meanwhile, it is important to know to what extent clinicians are aware of and follow clinical guidelines, and to determine the incidence of PONV, late-onset PONV and PDNV in our hospitals. This will enable us to maximise implementation of these recommendations according to the characteristics of each centre. At the individual level, we should ascertain the preferences of the patient and their baseline risk of PONV. We can then reduce this risk with anaesthesia and administer antiemetic prophylaxis proportional to the risk, bearing in mind that prevention is always better and more cost-effective than cure. Each patient is unique and different. Understanding their risk of PONV and the recommendations of clinical guidelines will allow us to choose between administering general multimodal prophylaxis or taking a more aggressive approach in certain circumstances (very high-risk patients or surgeries in which vomiting and retching will lead to complications), particularly considering the low cost of most currently used antiemetic, and their excellent safety profile.Ethical responsibilitiesProtection of human and animal rightsThe authors declare that no experiments were performed on humans or animals for this study.Data confidentialityThe authors declare that no patient data appears in this article.Right to privacy and informed consentThe authors declare that no patient data appears in this article.Conflict of interestsThe authors have no conflict of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres821538" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec818543" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres821537" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec818542" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Pathophysiology of PONV" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Risk factors, prognostic scales and pattern of occurrence" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Prevention and treatment" "secciones" => array:4 [ 0 => array:3 [ "identificador" => "sec0025" "titulo" => "Pharmacological strategies" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0030" "titulo" => "Serotonin receptor antagonists (5-HT) or setrons" ] 1 => array:2 [ "identificador" => "sec0035" "titulo" => "Corticoids" ] 2 => array:2 [ "identificador" => "sec0040" "titulo" => "Dopamine antagonists" ] 3 => array:2 [ "identificador" => "sec0045" "titulo" => "Muscarinic cholinergic antagonists" ] 4 => array:2 [ "identificador" => "sec0050" "titulo" => "H antihistimines: dexclorfeniramina, dimenhydrinate, diphenhydramine, cyclizine, meclizine" ] 5 => array:2 [ "identificador" => "sec0055" "titulo" => "Neurokinin receptor antagonists: aprepitant, casopitant, rolapitant, fosaprepitant and vestipitant" ] ] ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Non-pharmacological strategies" ] 2 => array:2 [ "identificador" => "sec0065" "titulo" => "Strategies proven to be ineffective, without sufficient evidence or that need further investigation" ] 3 => array:2 [ "identificador" => "sec0070" "titulo" => "Treatment of PONV" ] ] ] 8 => array:2 [ "identificador" => "sec0075" "titulo" => "Conclusions and recommendations" ] 9 => array:3 [ "identificador" => "sec0080" "titulo" => "Ethical responsibilities" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0085" "titulo" => "Protection of human and animal rights" ] 1 => array:2 [ "identificador" => "sec0090" "titulo" => "Data confidentiality" ] 2 => array:2 [ "identificador" => "sec0095" "titulo" => "Right to privacy and informed consent" ] ] ] 10 => array:2 [ "identificador" => "sec0100" "titulo" => "Conflict of interests" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec818543" "palabras" => array:5 [ 0 => "Postoperative nausea and vomiting" 1 => "Risk factors" 2 => "Antiemetics" 3 => "Risk score" 4 => "Emesis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec818542" "palabras" => array:5 [ 0 => "Náuseas y vómitos postoperatorios" 1 => "Factores de riesgo" 2 => "Antieméticos" 3 => "Escala de riesgo" 4 => "Emesis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Recognising the importance of the prevention and early treatment of postoperative nausea and vomiting (PONV) is essential to avoid postoperative complications, improve patient satisfaction and enable the development of major outpatient surgery and fast-track surgery. The topic of PONV might seem to have become stagnant, but we are moving forward. New concepts and problems like post-discharge nausea and vomiting, new risk factors and new drugs are appearing. However, there continue to be mistaken notions about PONV, such as the association between PONV and post-anaesthesia care unit stays, or assuming that it is a risk factor characteristic of the patient, anaesthesia or surgery when it is not. Perhaps, now is the moment to tackle PONV in a different manner, implementing guidelines and going for more aggressive prophylaxis in some groups of patients. We present an extensive review of this topic." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "Reconocer la importancia de prevenir y tratar precozmente las náuseas y los vómitos postoperatorios (NVPO) es fundamental para evitar complicaciones postoperatorias, mejorar la satisfacción del paciente y permitir el desarrollo de la cirugía mayor ambulatoria y de la cirugía fast-track. El tema de las NVPO podría parecer estancado, pero seguimos avanzando. Aparecen nuevos conceptos y problemas como las náuseas y vómitos postalta, nuevos factores de riesgo y nuevos fármacos. Por otro lado, siguen existiendo ideas erróneas, como asociar las NVPO con la estancia en la unidad de recuperación postanestésica o asumir como factores de riesgo características del paciente, de la anestesia o de la cirugía que realmente no lo son. Debemos enfrentarnos a las NVPO de otro modo, implementando el uso de las guías clínicas en nuestros centros y apostando por una profilaxis más agresiva en determinados grupos de pacientes. Presentamos a continuación una amplia revisión del tema." ] ] "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Veiga-Gil L, Pueyo J, López-Olaondo L. Náuseas y vómitos postoperatorios: fisiopatología, factores de riesgo, profilaxis y tratamiento. Rev Esp Anestesiol Reanim. 2017;64:223–232." ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program. An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page: www.elsevier.es/redar" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 2269 "Ancho" => 3067 "Tamanyo" => 438904 ] ] "descripcion" => array:1 [ "en" => "Pathophysiology retching/vomiting. AP: area postrema; CPG: central pattern generator; CVM: caudal ventrolateral medulla; RVM: rostral ventrolateral medulla; NTS: nucleus tractus solitarius; DNV: dorsal nucleus of the vagus; Vest N.: vestibular nuclei." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "PDNV: post-discharge nausea and vomiting; PONV: postoperative nausea and vomiting; PACU: post-anaesthesia care unit." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PONV risk factors \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PDNV risk factors (48h) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PDNV risk factors (days 3–7) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Women \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Women \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Duration of surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of PONV/motion sickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">History of PONV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">History of PONV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-smoker \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><50 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Use of ondansetron in PACU<a class="elsevierStyleCrossRef" href="#tblfn0005">a</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Postoperative opioids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Opioids in PACU Nausea in PACU \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Pain at 3–7 days \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1381298.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "Presence of postoperative nausea and vomiting in the post-anaesthesia care unit." ] ] ] "descripcion" => array:1 [ "en" => "Risk factors for postoperative and post-discharge nausea and vomiting from 48h until the seventh postoperative day." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "PDNV: post-discharge nausea and vomiting; PONV: postoperative nausea and vomiting; PACU: post-anaesthesia care unit." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apfel scale Risk factors \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total score \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PONV risk, % \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-smoking status \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of PONV/motion sickness \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Use of postoperative opioids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1381300.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apfel PDNV scale Risk factors \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Score \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total score \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PONV risk, % \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female gender \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age <50 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of PONV \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Use of opioids in PACU \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">60 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nausea in PACU \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">80 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1381301.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of the traditional Apfel postoperative nausea and vomiting risk scale for adult and the new Apfel post-discharge nausea and vomiting risk scale for patients undergoing outpatient surgery." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "MOS: major outpatient surgery; PONV: postoperative nausea and vomiting; TIVA: total intravenous anaesthesia." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Risk level \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Reduce baseline risk \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pharmacological prophylaxis</th></tr><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery without risk of complication if PONV \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery with risk of complications if PONV/MOS \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Very low or low 0–1 points ≤20% incidence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Only in surgery with risk of complications if PONV/MOS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monotherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate 2 points ≤40% incidence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes: general measures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Monotherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bitherapy \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">High or very high 3–4 points >40% incidence \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes: general measures. Consider TIVA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bitherapy \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Triple therapy \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1381299.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of recommended prophylaxis according to patient risk and type of surgery." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:50 [ 0 => array:3 [ "identificador" => "bib0255" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recomendaciones de prevención y tratamiento de las náuseas y vómitos postoperatorios y/o asociados a las infusiones de opioides" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.I. 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Postoperative nausea and vomiting: Physiopathology, risk factors, prophylaxis and treatment

Náuseas y vómitos postoperatorios: fisiopatología, factores de riesgo, profilaxis y tratamiento

L. Veiga-Gila,

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noraveigagil@gmail.com

Corresponding author.

, J. Pueyob, L. López-Olaondob

a Servicio de Anestesiología, Reanimación y Terapia del Dolor, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

b Departamento de Anestesiología y Cuidados Intensivos, Clínica Universidad de Navarra, Pamplona, Navarra, Spain

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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Pathophysiology retching&#47;vomiting&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">AP&#58; area postrema&#59; CPG&#58; central pattern generator&#59; CVM&#58; caudal ventrolateral medulla&#59; RVM&#58; rostral ventrolateral medulla&#59; NTS&#58; nucleus tractus solitarius&#59; DNV&#58; dorsal nucleus of the vagus&#59; Vest N&#46;&#58; vestibular nuclei&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Since the 1990s&#44; many scientific articles dealing with postoperative nausea and vomiting &#40;PONV&#41; have been published&#44; yet many authors remark on the scant progress made in this field in the past 20 years&#46; Nevertheless&#44; the research carried out has raised awareness of the problem and led to the development of prognostic scales&#44; protocols&#44; and even automatic systems for flagging high-risk patients based on their medical history&#46; Now&#44; for the first time in Spain&#44; a group of experts from the Spanish Society of Anaesthesiology published a suite of &#8220;recommendations for the prevention and treatment of PONV&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">1</span></a> It is important to bear in mind that new antiemetic drugs with better safety profiles are emerging&#44; and studies in the near future may determine their usefulness in controlling PONV&#46; Interestingly&#44; when talking to our patients we often find that many report severe PONV after their first anaesthetic experience&#44; but not in recent surgeries&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">This shows that progress is being made in preventing PONV&#46; So&#44; what is the problem today&#63; Firstly&#44; in the control of high-risk patients and highly emetogenic surgeries or procedures in which retching or vomiting may cause serious complications&#59; we simply cannot allow certain patients to experience PONV&#46; Incidence of PONV in the general surgical population is around 25&#37;&#8211;30&#37;&#44; and can increase to as much as 80&#37; in high-risk populations if they do not receive prophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a> The incidence in high-risk patients remains considerable &#40;60&#37;&#41;&#44; and affects their recovery insofar as it interferes with sleep and the start of the intake&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">3</span></a> &#8220;Clinically relevant&#8221; PONV &#40;3 or more emetic episodes&#44; or severe or long-term nausea&#41; is associated with more complications and poorer postoperative recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">4</span></a> Secondly&#44; there is the problem of late-onset PONV or post-discharge nausea and vomiting &#40;PDNV&#41; after outpatient surgery&#44; which has an incidence of about 45&#37; on the first day and up 6&#37; on day 7<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">5&#44;6</span></a> and is particularly hard to manage&#46; Risk factors and existing prognostic scales are not applicable to PDNV&#47;late-onset PONV&#44; and in these cases many antiemetics seem ineffective in the long term&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">6</span></a> Thirdly&#44; our specialty is particularly affected by decisions made by pharmaceutical companies and drug agencies&#44; as in the case of droperidol&#46; In addition&#44; some drugs used as antiemetics &#40;neuroleptics&#44; antihistamines&#44; corticosteroids&#44; etc&#46;&#41; were initially developed for other purposes but later found to be effective in this indication&#46; As such&#44; their antiemetic action is rarely included in the technical specifications of the product&#44; and this greatly complicates clinical research&#46; However&#44; the most important problem today is how to translate the enormous amount of scientific evidence into practical benefit for outpatients&#46; Clinical guidelines are notoriously hard to implement&#46; This and other situations have led to the current dilemma&#58; general multimodal vs scheduled risk-adopted prophylaxis based on prognostic scales&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">7</span></a> Our aim has been to summarise and organise the scientific evidence for PONV in order to contribute to our understanding of this problem in our setting&#44; and to bring us closer to the goal of &#8220;PONV-free&#8221; hospitals&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Pathophysiology of PONV</span><p id="par0015" class="elsevierStylePara elsevierViewall">The pathophysiology of nausea and vomiting is complex and not fully understood&#46; The first difficulty lies in the different pathophysiology of nausea with respect to vomiting&#46; In the case of nausea&#44; our knowledge is very limited&#46; We know that nausea is a conscious sensation involving cortical structures&#44; while vomiting is a complex reflex controlled by the medulla oblongata&#46; The act of vomiting involves a combination of emetic afferents and the coordinated action of respiratory&#44; gastrointestinal and abdominal muscles involved in the act of vomiting&#47;retching&#46; This entire process is controlled by what was formerly known as the vomiting centre&#46; The current hypothesis points to the existence of an organised group of neurons located in the medulla oblongata that are activated sequentially by the central pattern generator&#44; which coordinates the sequence of behaviours during emesis&#46; For vomiting to occur&#44; these neurons must be activated in the proper sequence&#44; which is why the notion of a &#8220;central pattern generator&#8221; is more acceptable than a &#8220;vomiting centre&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">8</span></a> Although the main neuronal groups that stimulate the central pattern generator are not well defined&#44; the nucleus tractus solitarius &#40;NTS&#41; and other specific nuclei of the reticular formation &#40;including respiratory nuclei&#41; are believed to be important sites for generating emesis&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">9</span></a> The NTS activates the central pattern generator and the surrounding neuronal groups that trigger the autonomic and motor response of vomiting &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">Four pathways activate vomiting by direct projections to the NTS&#58; &#40;1&#41; gastrointestinal tract &#40;GIT&#41; vagal afferent fibres&#44; &#40;2&#41; the vestibular system&#44; &#40;3&#41; the cerebral cortex&#44; thalamus and hypothalamus&#44; and &#40;4&#41; the area postrema &#40;AP&#41;&#46; Vagal afferent fibres of the GIT are excited by serotonin &#40;5-HT&#41; released from enteroendocrine cells when they detect circulating drugs or local toxins in the GI tract&#46; Vestibular nuclei receive motion-related sensory input&#46; Activation of the cerebral cortex and areas of the thalamus and hypothalamus trigger psychogenic-related vomiting and vomiting secondary to visual or olfactory stimuli&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">Research has gradually confirmed the importance of the AP and its chemoreceptor trigger zone&#46; The AP is a richly vascularised medullary structure located at the base of the fourth ventricle&#44; which lacks a specific blood&#8211;brain barrier&#46; Because of these characteristics&#44; its chemoreceptors are sensitive to emetogenic agents in the blood and the cerebrospinal fluid&#44; and it therefore plays a key role in drug-induced emesis&#46; Information from emetic afferents is transmitted to the AP via various pathways&#58; &#40;1&#41; direct visceral afferents via the vagus nerve&#44; &#40;2&#41; blood flow&#44; and &#40;3&#41; autonomic stimuli from descending pathways from the hypothalamus&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Ultimately&#44; afferents activate the vagus nerve and neuronal groups associated with nausea and vomiting through various neurotransmitters&#46; Five such neurotransmitters have been identified so far&#58; 5-HT&#44; dopamine &#40;D&#41;&#44; histamine &#40;H&#41;&#44; substance P&#44; acetylcholine and opioids&#46; Their corresponding receptors are located in vagal afferents &#40;5-HT<span class="elsevierStyleInf">3</span> receptors&#41;&#44; the vestibular nucleus &#40;M<span class="elsevierStyleInf">3</span>&#47;M<span class="elsevierStyleInf">5</span> muscarinic acetylcholine receptors and H<span class="elsevierStyleInf">1</span> receptors&#41;&#44; the AP &#40;&#956;-&#44; 5-HT<span class="elsevierStyleInf">3</span>- and D<span class="elsevierStyleInf">2</span>-opioid receptors&#41; and the NTS &#40;&#956; receptors&#44; 5-HT<span class="elsevierStyleInf">3</span>&#44; neurokinin-1 &#91;NK-1&#93;&#44; and the substance P receptor&#41;&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Risk factors&#44; prognostic scales and pattern of occurrence</span><p id="par0035" class="elsevierStylePara elsevierViewall">Due to the multifactorial origin of PONV&#44; any potential risk factor must be weighed up against other possible co-existing risk factors in order to avoid analytical errors&#46; The first articles studying multiple risk factors using logistic regression models date from the 1990s&#46; Until then&#44; researchers had focused on the study of risk factors in isolation&#44; without the influence of other variables&#46; This meant that the real effect of the factor was uncertain&#44; and led to flawed beliefs&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The most important limitation in the study of risk factors is the difficulty in differentiating between PONV risk factors and confounders&#46; A limited understanding of the pathophysiology can easily lead to confusion between cause and association&#58; is gynaecological surgery an independent risk factor for PONV&#63; Or is it a confounding factor&#44; and the real risk factor is female sex&#63; Is the use of opioids an independent risk factor&#63; Or is it the pain associated with certain types of surgeries that causes PONV and higher opioid requirements&#63; In 2012&#44; using all the scientific evidence available at that time&#44; Apfel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">10</span></a> published a meta-analysis of PONV risk factors to show which are independent predictors and which are not&#46; Among all the risk factors put forward at that time&#44; sufficient evidence was only available to confirm the following as independent predictors of PONV&#58;</p><p id="par0045" class="elsevierStylePara elsevierViewall">For postoperative nausea&#47;PONV&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patient-specific predictors&#58; <span class="elsevierStyleItalic">Female gender</span> &#40;<span class="elsevierStyleItalic">odds ratio</span> &#91;OR&#93; 2&#46;57&#41;&#44; <span class="elsevierStyleItalic">history of PONV&#47;motion sickness</span> &#40;OR 2&#46;09&#41;&#44; <span class="elsevierStyleItalic">non-smoking status</span> &#40;OR 1&#46;82&#41;&#44; <span class="elsevierStyleItalic">history of motion sickness</span> &#40;OR 1&#46;77&#41; and <span class="elsevierStyleItalic">age</span> &#40;OR 0&#46;88 per decade&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0055" class="elsevierStylePara elsevierViewall">Anaesthesia-related predictors&#58; use of <span class="elsevierStyleItalic">volatile anaesthetics</span> &#40;OR 1&#46;82&#41;&#44; <span class="elsevierStyleItalic">duration of anaesthesia</span> &#40;OR 1&#46;46 per hour&#41;&#44; use of <span class="elsevierStyleItalic">nitrous oxide</span> &#40;OR 1&#46;45&#41; and <span class="elsevierStyleItalic">postoperative use of opioids</span> &#40;OR 1&#46;39&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#8226;</span><p id="par0060" class="elsevierStylePara elsevierViewall">Surgery-related predictors&#58; <span class="elsevierStyleItalic">cholecystectomy</span> &#40;OR 1&#46;90&#41;&#44; <span class="elsevierStyleItalic">laparoscopic procedures</span> &#40;OR 1&#46;37&#41; and <span class="elsevierStyleItalic">gynaecological surgery</span> &#40;OR 1&#46;24&#41;&#46;</p></li></ul></p><p id="par0065" class="elsevierStylePara elsevierViewall">For postoperative vomiting&#58; predictors were similar to those of postoperative nausea&#47;PONV&#44; particularly&#58; <span class="elsevierStyleItalic">female gender</span> &#40;OR 2&#46;73&#41;&#44; <span class="elsevierStyleItalic">history of PONV&#47;motion sickness</span> &#40;OR 2&#46;32&#41;&#44; <span class="elsevierStyleItalic">non-smoking</span> status &#40;OR 1&#46;78&#41;&#46; In the case of postoperative vomiting&#44; neither age nor any of the types of surgery analysed were significant enough to warrant consideration as a predictor&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Clinical guidelines published in 2014 confirmed the risk factors discussed so far&#44; and added <span class="elsevierStyleItalic">age &#60;50</span> and <span class="elsevierStyleItalic">general anaesthesia</span> &#40;incidence of PONV 9 times greater than in regional anaesthesia<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a>&#41;&#46; The latest evidence shows that <span class="elsevierStyleItalic">nitrous oxide has a time-dependent</span> emetic effect&#44; with the risk of PONV increasing by 20&#37; per hour from the first 45<span class="elsevierStyleHsp" style=""></span>min of exposure&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">11</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Much progress has been made recently in the study of <span class="elsevierStyleItalic">genetic predisposition</span> and PONV&#46; A familial pattern of PONV and antiemetic resistance has been observed that seems to be due to polymorphisms in the genes encoding some receptors&#44; such as A and B subunits of the 5-HT receptor &#40;5-HT<span class="elsevierStyleInf">3A</span> and 5-HT<span class="elsevierStyleInf">3B</span>&#41;&#44; M<span class="elsevierStyleInf">3</span> muscarinic receptors and the NK-1 receptor&#46; Other recently confirmed risk factors are <span class="elsevierStyleItalic">chemotherapy-induced nausea and vomiting &#40;CINV&#41;</span>&#46; A history of CINV is a predictor of PONV&#44; and a 2015 study showed that cancer patients with a history of CINV were more likely to present PONV when undergoing surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">12</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Risk factors for PONV&#44; PDNV&#44; and late-onset PONV are not exactly the same&#46; Studies published by Apfel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">6</span></a> and Odom-Forren et al&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">5</span></a> have contributed to our understanding of the risk factors of PONV &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46; We also know that the causes of PONV in the first 48 postoperative hours and PONV at 3 days are different&#46; To date&#44; the following risk factors have been shown to be independent predictors for NVPA<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">6</span></a>&#58; <span class="elsevierStyleItalic">female gender&#44; age under 50 years&#44; history of PONV&#44; use of opioids in the postanaesthesia care unit &#40;PACU&#41;&#44; and nausea in the PACU</span>&#46; <span class="elsevierStyleItalic">Pain</span> is the most important risk factor associated with late-onset PONV&#44; occurring between days 3 and 7 after major outpatient surgery &#40;MOS&#41;&#46; It is important to note that neither the <span class="elsevierStyleItalic">type of surgery</span> nor <span class="elsevierStyleItalic">non-smoking status</span> are independent predictors of PONV&#46; Patients presenting nausea in the PACU have a three-fold risk of PONV&#46; It should also be noted that the use of intraoperative ondansetron decreases the incidence of PONV in the PACU but not after discharge&#44; and the opposite occurs with corticosteroids&#44; which do not seem to have a protective effect in the PACU&#44; but do protect against PDNV&#46; Total intravenous anaesthesia has an antiemetic effect only during the first postoperative hours&#44; and therefore should not replace the administration of antiemetics in MOS patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">6&#44;13</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">Menstrual cycle&#44; mask ventilation and the expertise of the anaesthetist&#44; use of neostigmine&#44; BMI&#44; anxiety&#44; fraction of inspired oxygen&#44; use of a nasogastric tube&#44; <span class="elsevierStyleItalic">American Society of Anesthesiologists</span> &#40;ASA&#41; physical status score&#44; preoperative fasting and migraines have all been ruled out as risk factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">2&#44;10</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Risk factors are used to create prognostic scales&#44; which allow clinicians to classify patients according to their risk of PONV and to decide whether to prevent or treat the condition&#44; and how&#46; One such scale&#44; the simplified Apfel scale &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41; was developed in the 1990s&#46; This scale proved to be as effective as its predecessors&#44; but because it is simplified and weighs each risk factor equally&#44; it is easily applied and is currently the most widely used tool&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">14</span></a> It is important to bear in mind that these prognostic scales were designed and validated in adults undergoing surgery under balanced general anaesthesia&#44; and are therefore only valid in similar situations&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The Eberhart scale is used in paediatric patients&#44; with the recent addition of the Bourdaud scale&#44; which has a high predictive value but is awaiting external validation&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">15</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">As discussed&#44; neither risk factors nor conventional prognostic scales have been shown to be predictive of PDNV&#46; In 2012&#44; Apfel et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">6</span></a> published a prognostic scale for PDNV based on the following factors&#58; <span class="elsevierStyleItalic">female gender&#44; age &#60;50 years&#44; history of PONV&#44; use of opioids in the PACU and nausea in the PACU</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">It is not only important to predict the risk of PONV&#44; but also to predict when it will occur&#46; The widespread notion that PONV is a complication in the immediate postoperative period is unfounded&#46; PONV can onset at any time during the first 72 postoperative hours&#46; In hospitalised patients&#44; incidence peaks at between 2 and 12<span class="elsevierStyleHsp" style=""></span>h after surgery&#44; and it is therefore a complication that occurs most often in the hospital ward and not in the PACU&#44; as previously believed&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">16</span></a> PDNV has been described in MOS patients up to 7 days post surgery&#44; and a key factor seems to be the ride home from the hospital&#44; with incidence peaking during this trip and on arrival home on the day of surgery&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">5</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Prevention and treatment</span><p id="par0110" class="elsevierStylePara elsevierViewall">There are currently various schools of thought in respect of PONV prophylaxis&#58; <span class="elsevierStyleItalic">general multimodal vs scheduled risk-adopted prophylaxis&#46;</span><a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">17</span></a> According to clinical guidelines&#44; the safest and most cost-effective approach is scheduled risk-adapted prophylaxis based on prognostic scales&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">1</span></a> but this seems to have done little to reduce the current incidence of PONV &#40;20&#37;&#8211;30&#37;&#41;&#44; especially in high-risk patients&#46; Matters are further aggravated by poor adherence to the recommendations of clinical guidelines in daily practice&#44; and the modest predictive power of prognostic scales&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">7</span></a> To overcome this&#44; some authors&#44; citing the low cost of current antiemetic agents and their excellent safety profile&#44; defend the general multimodal prophylaxis approach&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">18</span></a> Others propose an intermediate&#44; and probably more sensible&#44; solution&#58; apply predictive models along with a therapeutic recommendation for the type of prophylaxis to be administered&#46; This would increase the number of antiemetics administered and decrease the incidence of PONV&#44; especially in high-risk patients&#46; This&#44; together with lowering the risk threshold for prophylaxis administration&#44; would reduce the current incidence of PONV&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">19</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">The following is a summary of the recommendations of the ASA<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a> and the Spanish Society of Anesthesiology&#44;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">1</span></a> slightly adapted to make them applicable to cases of MOS patients and procedures in which vomiting or retching increases the risk of complications&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Step 1&#58; <span class="elsevierStyleItalic">Identify the patient&#39;s risk</span> for PONV by applying the Apfel prognostic scale&#46; Prophylaxis should be administered in sufficiently high-risk patients&#46; A more liberal use of prophylaxis is warranted in outpatient surgery and in patients in whom vomiting or retching would lead to considerable clinical risk &#40;mandibular sutures following maxillofacial surgery&#44; risk of bleeding due to retching-induced increase in intracranial pressure following neurosurgery&#44; or eosophagogastric surgery&#41;&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Step 2&#58; <span class="elsevierStyleItalic">reduce the baseline risk</span> by applying general strategies&#46; The following are the recommendations given in the latest clinical guidelines with their level of evidence &#40;evidence grading system used by the ASA in previous clinical guidelines for perioperative pain and PONV&#41;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a>&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Choose regional anaesthesia over general anaesthesia &#40;A1&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Use propofol for TIVA induction and maintenance &#40;A1&#41;&#46; Propofol is associated with a lower incidence of PONV in the first 6 postoperative hours&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Avoid the use of nitrous oxide &#40;A1&#41; and volatile anaesthetics &#40;A2&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0145" class="elsevierStylePara elsevierViewall">Minimise the use of intraoperative opioids &#40;A2&#41; and postoperative opioids &#40;A1&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0150" class="elsevierStylePara elsevierViewall">Adequate hydration &#40;A1&#41;&#46; Administration of IV fluids at 30<span class="elsevierStyleHsp" style=""></span>mL&#47;kg in surgeries associated with blood loss reduces the overall incidence of PONV&#44; irrespective of the type of fluid used&#46;</p></li></ul></p><p id="par0155" class="elsevierStylePara elsevierViewall">Step 3&#58; administer prophylaxis in proportion to the calculated risk&#44; as shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0160" class="elsevierStylePara elsevierViewall">Step 4&#58; <span class="elsevierStyleItalic">treat PONV if it appears&#44; and assess the need for antiemetic prophylaxis or treatment at discharge in MOS patients</span>&#46; Although several studies have been published with different combinations of antiemetics for PDNV prophylaxis&#44; these are not evidence-based&#44; and some of the antiemetics studied are not available in Spain&#46; It is important to note that <span class="elsevierStyleItalic">PONV and&#47;or requirement of opioids in the PACU</span> are risk factors for PDNV&#44; and one of the antiemetics studied that may be used in Spain is 8<span class="elsevierStyleHsp" style=""></span>mg oral ondansetron immediately before discharge and in the morning of the first and second postoperative day&#44; in addition to daily telephone follow-up&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">2&#44;20</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Pharmacological strategies</span><p id="par0165" class="elsevierStylePara elsevierViewall">Several studies have shown the efficacy of antiemetic combinations vs monotherapy&#46; The combination of antiemetics with different mechanism of action has a cumulative effect in reducing the appearance of PONV&#44; and each administration reduces incidence by 25&#37;&#8211;30&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">21</span></a></p><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Serotonin receptor antagonists &#40;5-HT<span class="elsevierStyleInf">3</span>&#41; or <span class="elsevierStyleItalic">setrons</span></span><p id="par0170" class="elsevierStylePara elsevierViewall">These block the action of 5-HT receptors in the AP&#44; NTS and GIT vagal afferents&#46; Drugs in this group includes&#58; <span class="elsevierStyleItalic">ondansetron</span>&#44; <span class="elsevierStyleItalic">granisetron</span>&#44; <span class="elsevierStyleItalic">dolasetron</span>&#44; <span class="elsevierStyleItalic">tropisetron</span>&#44; <span class="elsevierStyleItalic">ramosetron</span> and <span class="elsevierStyleItalic">palonosetron</span>&#46; Ondansetron is the most widely studied and the &#8220;gold standard&#8221; compared with other antiemetics&#44; as it has proven to be the most cost-effective of all &#40;evidence level A1&#41;&#46; It is recommended at an IV dose of 4<span class="elsevierStyleHsp" style=""></span>mg at the end of surgery&#44; and has a half-life of 4<span class="elsevierStyleHsp" style=""></span>h&#46; It is usually considered more effective against vomiting than nausea&#44; although the evidence is inconsistent&#46; It has a number needed to treat &#40;NNT&#41; of approximately 6 for prevention of vomiting and 7 for prevention of nausea&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">22</span></a> The most common adverse reactions are headache &#40;number needed to harm &#91;NNH&#93; 36&#41;&#44; subclinical elevation of hepatic enzymes &#40;NNH 31&#41; and constipation &#40;NNH 23&#41;&#46; Setrons &#40;except palonosetron&#41; have been shown <span class="elsevierStyleItalic">in vitro</span> to block sodium channels and can prolong the QT interval&#46; In clinical practice&#44; ondansetron&#44; tropisetron and granisetron can have the dose-dependent effect of prolonging the QT interval and decreasing heart rate&#44; although there is a growing body of evidence to show that QT prolongation is minor and of little clinical consequence&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">23</span></a> The use of 5-HT antagonists in combination with dexamethasone or droperidol has also been shown to be as safe as monotherapy&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">24</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Palonosetron at an IV dose of 0&#46;075<span class="elsevierStyleHsp" style=""></span>mg is effective&#44; well tolerated&#44; and approved by the Food and Drug Administration &#40;FDA&#41;&#46; Compared with ondansetron 8<span class="elsevierStyleHsp" style=""></span>mg&#44; it proved more effective in the prophylaxis of PONV at 24 and 72<span class="elsevierStyleHsp" style=""></span>h<span class="elsevierStyleMonospace">&#44;</span> with a lower incidence of headache and less need for rescue antiemetics&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">25</span></a> In Spain&#44; it is only approved for PONV&#46; Recent interest in palonosetron stems from the fact that it does not prolong the QT interval&#44; has a longer half-life &#40;40<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; and binds to the 5-HT receptor in such a way as to cause conformational changes&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">26</span></a> Because of this&#44; some authors recommend it as one of the options for PONV prophylaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Corticoids</span><p id="par0180" class="elsevierStylePara elsevierViewall">Dexamethasone has proven effective as an antiemetic in multiple clinical trials&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a> It is usually administered at an IV dose of 8<span class="elsevierStyleHsp" style=""></span>mg &#40;NNT<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>4&#41;&#44; but following the multicentre IMPACT study and systematic reviews&#44;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">21</span></a> some guidelines recommend 4&#8211;5<span class="elsevierStyleHsp" style=""></span>mg &#40;evidence level A1&#41;&#46; A recent meta-analysis has shown that in terms of antiemetic efficacy&#44; 4&#8211;5<span class="elsevierStyleHsp" style=""></span>mg is as effective as 8&#8211;10<span class="elsevierStyleHsp" style=""></span>mg&#44; although dexamethasone 8<span class="elsevierStyleHsp" style=""></span>mg improves the quality of postoperative recovery&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">29</span></a> The dose in children is 0&#46;15<span class="elsevierStyleHsp" style=""></span>mg&#47;kg &#40;up to 5<span class="elsevierStyleHsp" style=""></span>mg&#41;&#46; Its antiemetic mechanism of action is not entirely understood&#44; but several theories have been put forward&#44; including&#58; inhibition of arachidonic acid and prostaglandins&#44; inhibition of 5-HT release in the GIT&#44; reduction of 5-HT precursor expression in the central nervous system&#44; changes in blood&#8211;brain barrier permeability to serum proteins&#44; release of endorphins&#44; or boosting the effect of other antiemetics by enhancing the sensitivity of 5-HT receptors and acting directly on the NTS by activating glucocorticoid receptors&#46; Despite these differences&#44; there is widespread consensus that it must be administered during anaesthesia induction&#44; due to its slow onset of action &#40;2<span class="elsevierStyleHsp" style=""></span>h&#41;&#46; It has a prolonged effect &#40;72<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; and no adverse effects have been reported&#46; The only relative contraindication for dexamethasone is administration in diabetic or obese patients&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a> In terms of secondary hyperglycaemia&#44; evidence suggests that blood glucose increase is similar in type 2 diabetics and nondiabetics&#44; and is mainly due to surgical stress&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">30</span></a> Neither has dexamethasone use been associated with increased surgical wound infection or major bleeding&#46; IV administration cause perineal pruritus&#46; Because of its duration of action and safety profile&#44; it is highly recommended in MOS patients&#46; Methylprednisolone has also been shown to be an effective anti-emetic in IV doses of 40<span class="elsevierStyleHsp" style=""></span>mg&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Dopamine antagonists</span><p id="par0185" class="elsevierStylePara elsevierViewall">Droperidol blocks the action of D<span class="elsevierStyleInf">2</span> receptors in the AP&#46; The recommended IV dose is 0&#46;625&#8211;1&#46;25<span class="elsevierStyleHsp" style=""></span>mg&#44; and it has an NNT of 5 &#40;evidence level A1&#41;&#44; although a recent meta-analysis shows that low doses &#40;&#8804;1<span class="elsevierStyleHsp" style=""></span>mg&#41; are effective&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">32</span></a> It should be administered at the end of surgery&#46; Droperidol has a half-life of 2&#8211;3<span class="elsevierStyleHsp" style=""></span>h&#46; Following an FDA warning in 2001 on the risk of arrhythmias&#44; droperidol was withdrawn from hospitals in Spain&#46; In 2009&#44; it was re-introduced for the prevention and treatment of PONV and morphine-related nausea and vomiting &#40;NNT<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3&#41;&#46; According to the FDA&#44; electrocardiographic monitoring is required for 2&#8211;3<span class="elsevierStyleHsp" style=""></span>h after administration&#46; The effect of droperidol on the QT does not increase when administered in combination with ondansetron&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">33</span></a> If it were not for the FDA alert&#44; ASA clinical guidelines would recommend droperidol as a first line antiemetic in PONV prophylaxis&#46; The Spanish Society of Anaesthesiology guidelines&#44; however&#44; do recommend it as a first-line drug&#44; with ondansetron as a rescue remedy&#46; Evidence has shown that current prophylactic doses are not associated with severe cardiac events&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">34</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">Droperidol is the most widely recommended drug for opioid-induced PONV&#44; and it is the only drug with this indication in Spain&#46; Guidelines recommend adding droperidol to intravenous patient-controlled analgesia&#44; at a dose of 0&#46;1<span class="elsevierStyleHsp" style=""></span>mg per milligram morphine&#44; with a maximum of 4<span class="elsevierStyleHsp" style=""></span>mg of droperidol daily&#44; although the minimum effective dose has yet to be confirmed&#46; These doses reduce both incidence of PONV and morphine requirements&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">35</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">Low-dose &#40;0&#46;5&#8211;2<span class="elsevierStyleHsp" style=""></span>mg IV or IM&#41; haloperidol is recommended as an antiemetic&#44; with an NNT of 4 and 6 for nausea and vomiting&#44; respectively&#46; Its effectiveness is comparable to that of ondansetron or droperidol&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">36</span></a> It has a longer half-life than droperidol &#40;16<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; but is less specific for the D<span class="elsevierStyleInf">2</span> receptor and there is no evidence for the best timing of administration and the lowest effective dose&#44; as some studies have shown limited effectiveness for low-dose haloperidol&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">16</span></a> It is also associated with QT prolongation&#44; although evidence shows that it is safe at low doses&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a> The incidence of adverse reactions to neuroleptics is dose-proportional&#46; Droperidol is as well tolerated as setrons&#44; but provides more sedation &#40;in a dose dependent manner&#41;&#46; Administration of neuroleptics at higher than recommended doses can cause anxiety&#44; restlessness&#44; extrapyramidal symptoms and even neuroleptic malignant syndrome&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Muscarinic cholinergic antagonists</span><p id="par0200" class="elsevierStylePara elsevierViewall">Interest in the transdermal scopolamine patch&#44; originally designed to treat motion sickness&#44; has recently been rekindled&#46; Because of its low onset of action &#40;2&#8211;4<span class="elsevierStyleHsp" style=""></span>h&#41;&#44; the patch &#40;1&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#41; is applied 4<span class="elsevierStyleHsp" style=""></span>h before surgery&#44; providing sustained release for 72<span class="elsevierStyleHsp" style=""></span>h&#46; Theoretically&#44; it causes a high incidence of cholinergic adverse events &#40;dry mouth&#44; blurred vision&#44; agitation&#44; dysphoria&#44; dizziness&#44; confusion&#44; etc&#46;&#41;&#44; although the latest studies suggest a far lower incidence&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">38</span></a> Adverse reactions may be more common in children and the elderly&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">H<span class="elsevierStyleInf">1</span> antihistimines&#58; dexclorfeniramina&#44; dimenhydrinate&#44; diphenhydramine&#44; cyclizine&#44; meclizine</span><p id="par0205" class="elsevierStylePara elsevierViewall">These drugs are less common due to their sedative effect&#46; They have shown efficacy in some studies&#44; but have not been widely studied as other antiemetics&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">39</span></a> According to the latest guidelines&#44; they are not considered first-line drugs in the prophylaxis of PONV&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a> The most common adverse reactions are dry mouth&#44; blurred vision&#44; sedation&#44; and urinary retention&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Neurokinin receptor antagonists&#58; aprepitant&#44; casopitant&#44; rolapitant&#44; fosaprepitant and vestipitant</span><p id="par0210" class="elsevierStylePara elsevierViewall">Substance P is a neuropeptide involved in the pathophysiology of nausea and vomiting because it binds to NK-1 receptors in the central and peripheral nervous system&#46; These drugs competitively inhibit the action of substance P and act both centrally &#40;by blocking neurotransmission in the NTS&#41; and peripherally &#40;by blocking NK1 receptors located on vagal terminals in the gut&#41; to decrease the intensity of the emetic afferent message and prevent nausea and vomiting&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">40</span></a> The only FDA-approved drug in this group for PONV is aprepitant&#46; Aprepitant has a half-life of 40<span class="elsevierStyleHsp" style=""></span>h&#44; and the recommended prophylaxis dose is 40<span class="elsevierStyleHsp" style=""></span>mg po 1&#8211;3<span class="elsevierStyleHsp" style=""></span>h before surgery&#46; These drugs are well tolerated and do not cause sedation or QT prolongation&#46; Aprepitant is comparable to ondansetron in efficacy&#44; and is more effective in reducing nausea severity in the first 48<span class="elsevierStyleHsp" style=""></span>h&#44; and in preventing vomiting at 24 and 48<span class="elsevierStyleHsp" style=""></span>h postoperatively&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">40</span></a> NK1 inhibitors may be an attractive option for controlling late-onset PONV&#47;PDNV&#44; and in patients that have not responded to other antiemetics&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">27</span></a> The only NK1 inhibitor available in Spain is aprepitant&#44; at a recommended dose of 80 and 125<span class="elsevierStyleHsp" style=""></span>mg for CINV&#46;</p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Non-pharmacological strategies</span><p id="par0215" class="elsevierStylePara elsevierViewall">Non-pharmacological PONV management strategies include acupuncture&#44; electroacupuncture&#44; acupressure&#44; transcutaneous electrical stimulation&#44; and hypnosis&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">41</span></a> Several studies have evaluated the efficacy of P6 point stimulation in preventing PONV&#44; but results are inconclusive&#46; Some authors report a reduction in incidence and intensity of PONV during the first 6 postoperative hours compared with placebo&#44; and it has been shown to be as effective as any of the most widely used antiemetics&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">42</span></a> Although easy to implement&#44; the reason these measures are not used in clinical practice could be that we are unfamiliar with such techniques&#44; the recommendations for their use are unclear&#44; there is insufficient evidence&#44; and because drugs are so much easier to administer&#46; However&#44; since they have proved effective in some cases&#44; they should be included in the multimodal approach to PONV&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">43</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Strategies proven to be ineffective&#44; without sufficient evidence or that need further investigation</span><p id="par0220" class="elsevierStylePara elsevierViewall">There are basically 3 drugs that should be discussed in this context&#58; metoclopramide&#44; midazolam and gabapentin&#46; Although commonly used as an antiemetic&#44; evidence shows that IV metoclopramide 10<span class="elsevierStyleHsp" style=""></span>mg is not effective for prophylaxis of PONV because the dose used is too low&#44; and higher doses increase the risk of side effects&#44; particularly extrapyramidal symptoms&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">44</span></a> Midazolam and gabapentin warrant special mention&#44; as they have hitherto been included in the &#8220;insufficient evidence&#8221; group&#46; However&#44; recent meta-analyses and clinical trials have shown that preoperative oral gabapentin 600<span class="elsevierStyleHsp" style=""></span>mg and preoperative IV midazolam 2&#8211;5<span class="elsevierStyleHsp" style=""></span>mg are effective in the prophylaxis of PONV&#46;<a class="elsevierStyleCrossRefs" href="#bib0475"><span class="elsevierStyleSup">45&#44;46</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Treatment of PONV</span><p id="par0225" class="elsevierStylePara elsevierViewall">Recurrence after a first&#44; untreated&#44; episode of PONV can be as high as 84&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">47</span></a> Therefore&#44; aggressive measures must be taken if prophylaxis fails and the patient presents PONV&#46; Generally speaking&#44; the same drugs as used for PONV prophylaxis can be used in treatment&#59; combinations can also be used&#46; It is important to choose the antiemetic rescue remedy in accordance with the prophylaxis administered&#44; in other words&#44; the drug used as first-line rescue must belong to a different class of medicines as that used for prophylaxis if it is administered less than 6<span class="elsevierStyleHsp" style=""></span>h after the prophylaxis&#46; The only exceptions to this rule are <span class="elsevierStyleItalic">dexamethasone&#44; scopolamine patches&#44; aprepitant and palonosetron</span>&#44; which&#44; because of their long half-life&#44; should not be repeated&#46; If antiemetic prophylaxis was not administered&#44; PONV should be treated with low-dose 5-HT<span class="elsevierStyleInf">3</span> antagonists&#44; the most widely studied of these being IV ondansetron at a therapeutic dose of 1<span class="elsevierStyleHsp" style=""></span>mg&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">48</span></a> IV droperidol at doses ranging from 0&#46;625 to 1&#46;25<span class="elsevierStyleHsp" style=""></span>mg is also effective&#46; There are insufficient data on dexamethasone&#46; Its efficacy as first-line treatment of PONV is questionable because of its slow onset of action&#44; but it could be useful in combination with other antiemitics&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a> Low-dose IV propofol &#40;10<span class="elsevierStyleHsp" style=""></span>mg&#41; seems to be effective&#44; although it has a shorter duration of action than the more widely used antiemetics&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a> A less common approach&#44; but one that could be considered in some cases&#44; is to change to another 5-HT<span class="elsevierStyleInf">3</span> antagonist&#46; Because setrons are metabolised by different isoenzymes&#44; some patients that do not respond to ondansetron may respond to granisetron&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">49</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Although IV midazolam &#40;2&#8211;5<span class="elsevierStyleHsp" style=""></span>mg&#41; does not seem to have taken its place in the PONV toolbox&#44; there is both evidence and clinical experience to support its efficacy&#44;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">50</span></a> above all in patients with intense nausea that does not respond to conventional antiemetics&#46; Neither should we forget the antiemetic properties of antihistamines&#44; such as dexclorfeniramina&#44; despite a high incidence of adverse effects&#44; such as somnolence&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions and recommendations</span><p id="par0235" class="elsevierStylePara elsevierViewall">PONV is not life-threatening&#44; but it is nevertheless common and difficult to control&#44; especially in high-risk and MOS patients&#46; New generation&#44; long-acting antiemetics &#40;aprepitant&#44; palonosetron or scopolamine patches&#41; recommended for the management of late-onset PONV&#47;PDNV&#44; particularly the latest additions&#44; are not available in Spain&#46; The future availability of these drugs will be decided by the pharmaceutical industry&#46; Meanwhile&#44; it is important to know to what extent clinicians are aware of and follow clinical guidelines&#44; and to determine the incidence of PONV&#44; late-onset PONV and PDNV in our hospitals&#46; This will enable us to maximise implementation of these recommendations according to the characteristics of each centre&#46; At the individual level&#44; we should ascertain the preferences of the patient and their baseline risk of PONV&#46; We can then reduce this risk with anaesthesia and administer antiemetic prophylaxis proportional to the risk&#44; bearing in mind that prevention is always better and more cost-effective than cure&#46; Each patient is unique and different&#46; Understanding their risk of PONV and the recommendations of clinical guidelines will allow us to choose between administering general multimodal prophylaxis or taking a more aggressive approach in certain circumstances &#40;<span class="elsevierStyleItalic">very high</span>-risk patients or surgeries in which vomiting and retching will lead to complications&#41;&#44; particularly considering the low cost of most currently used antiemetic&#44; and their excellent safety profile&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Ethical responsibilities</span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Protection of human and animal rights</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Data confidentiality</span><p id="par0245" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Right to privacy and informed consent</span><p id="par0250" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appears in this article&#46;</p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conflict of interests</span><p id="par0255" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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          "titulo" => "Introduction"
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          "titulo" => "Pathophysiology of PONV"
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          "titulo" => "Risk factors&#44; prognostic scales and pattern of occurrence"
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          "titulo" => "Prevention and treatment"
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                  "titulo" => "Serotonin receptor antagonists &#40;5-HT&#41; or setrons"
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            0 => "Postoperative nausea and vomiting"
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            0 => "N&#225;useas y v&#243;mitos postoperatorios"
            1 => "Factores de riesgo"
            2 => "Antiem&#233;ticos"
            3 => "Escala de riesgo"
            4 => "Emesis"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Recognising the importance of the prevention and early treatment of postoperative nausea and vomiting &#40;PONV&#41; is essential to avoid postoperative complications&#44; improve patient satisfaction and enable the development of major outpatient surgery and fast-track surgery&#46; The topic of PONV might seem to have become stagnant&#44; but we are moving forward&#46; New concepts and problems like post-discharge nausea and vomiting&#44; new risk factors and new drugs are appearing&#46; However&#44; there continue to be mistaken notions about PONV&#44; such as the association between PONV and post-anaesthesia care unit stays&#44; or assuming that it is a risk factor characteristic of the patient&#44; anaesthesia or surgery when it is not&#46; Perhaps&#44; now is the moment to tackle PONV in a different manner&#44; implementing guidelines and going for more aggressive prophylaxis in some groups of patients&#46; We present an extensive review of this topic&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Reconocer la importancia de prevenir y tratar precozmente las n&#225;useas y los v&#243;mitos postoperatorios &#40;NVPO&#41; es fundamental para evitar complicaciones postoperatorias&#44; mejorar la satisfacci&#243;n del paciente y permitir el desarrollo de la cirug&#237;a mayor ambulatoria y de la cirug&#237;a <span class="elsevierStyleItalic">fast-track</span>&#46; El tema de las NVPO podr&#237;a parecer estancado&#44; pero seguimos avanzando&#46; Aparecen nuevos conceptos y problemas como las n&#225;useas y v&#243;mitos postalta&#44; nuevos factores de riesgo y nuevos f&#225;rmacos&#46; Por otro lado&#44; siguen existiendo ideas err&#243;neas&#44; como asociar las NVPO con la estancia en la unidad de recuperaci&#243;n postanest&#233;sica o asumir como factores de riesgo caracter&#237;sticas del paciente&#44; de la anestesia o de la cirug&#237;a que realmente no lo son&#46; Debemos enfrentarnos a las NVPO de otro modo&#44; implementando el uso de las gu&#237;as cl&#237;nicas en nuestros centros y apostando por una profilaxis m&#225;s agresiva en determinados grupos de pacientes&#46; Presentamos a continuaci&#243;n una amplia revisi&#243;n del tema&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Veiga-Gil L&#44; Pueyo J&#44; L&#243;pez-Olaondo L&#46; N&#225;useas y v&#243;mitos postoperatorios&#58; fisiopatolog&#237;a&#44; factores de riesgo&#44; profilaxis y tratamiento&#46; Rev Esp Anestesiol Reanim&#46; 2017&#59;64&#58;223&#8211;232&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar9010">This article is part of the Anaesthesiology and Resuscitation Continuing Medical Education Program&#46; An evaluation of the questions on this article can be made through the Internet by accessing the Education Section of the following web page&#58; <span class="elsevierStyleInterRef" id="intr9065" href="http://www.elsevier.es/redar">www&#46;elsevier&#46;es&#47;redar</span></p>"
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          "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Pathophysiology retching&#47;vomiting&#46;</p> <p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">AP&#58; area postrema&#59; CPG&#58; central pattern generator&#59; CVM&#58; caudal ventrolateral medulla&#59; RVM&#58; rostral ventrolateral medulla&#59; NTS&#58; nucleus tractus solitarius&#59; DNV&#58; dorsal nucleus of the vagus&#59; Vest N&#46;&#58; vestibular nuclei&#46;</p>"
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">PDNV&#58; post-discharge nausea and vomiting&#59; PONV&#58; postoperative nausea and vomiting&#59; PACU&#58; post-anaesthesia care unit&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PONV risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PDNV risk factors &#40;48<span class="elsevierStyleHsp" style=""></span>h&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Women&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Duration of surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of PONV&#47;motion sickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">History of PONV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">History of PONV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-smoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;50 years&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Pain at 3&#8211;7 days&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Risk factors for postoperative and post-discharge nausea and vomiting from 48<span class="elsevierStyleHsp" style=""></span>h until the seventh postoperative day&#46;</p>"
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">PDNV&#58; post-discharge nausea and vomiting&#59; PONV&#58; postoperative nausea and vomiting&#59; PACU&#58; post-anaesthesia care unit&#46;</p>"
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apfel scale<br>Risk factors&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PONV risk&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Non-smoking status&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of PONV&#47;motion sickness&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Use of postoperative opioids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1381300.png"
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            1 => array:2 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Apfel PDNV scale<br>Risk factors&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Total score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PONV risk&#44; &#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Female gender&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#60;50 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">History of PONV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Use of opioids in PACU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nausea in PACU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Comparison of the traditional Apfel postoperative nausea and vomiting risk scale for adult and the new Apfel post-discharge nausea and vomiting risk scale for patients undergoing outpatient surgery&#46;</p>"
        ]
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">MOS&#58; major outpatient surgery&#59; PONV&#58; postoperative nausea and vomiting&#59; TIVA&#58; total intravenous anaesthesia&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="table-head ; entry_with_role_rowhead " align="left" valign="top" scope="col">Risk level&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col">Reduce baseline risk&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Pharmacological prophylaxis</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery without risk of complication if PONV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Surgery with risk of complications if PONV&#47;MOS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Very low or low</span><br>0&#8211;1 points<br>&#8804;20&#37; incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Only in surgery with risk of complications if PONV&#47;MOS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Moderate</span><br>2 points<br>&#8804;40&#37; incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#58; general measures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Monotherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bitherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">High or very high</span><br>3&#8211;4 points<br>&#62;40&#37; incidence&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&#58; general measures&#46; Consider TIVA&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bitherapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Triple therapy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Summary of recommended prophylaxis according to patient risk and type of surgery&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:50 [
            0 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recomendaciones de prevenci&#243;n y tratamiento de las n&#225;useas y v&#243;mitos postoperatorios y&#47;o asociados a las infusiones de opioides"
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                          "etal" => true
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                            0 => "J&#46;I&#46; G&#243;mez-Arnau"
                            1 => "J&#46;L&#46; Aguilar"
                            2 => "P&#46; Bovaira"
                            3 => "F&#46; Bustos"
                            4 => "J&#46; de Andr&#233;s"
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                  "host" => array:1 [
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                      "Revista" => array:6 [
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                        "fecha" => "2010"
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                            "web" => "Medline"
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              "referencia" => array:1 [
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                      "titulo" => "Consensus guidelines for the management of postoperative nausea and vomiting"
                      "autores" => array:1 [
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                          "etal" => true
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                            0 => "T&#46;J&#46; Gan"
                            1 => "P&#46; Diemunsch"
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                  "host" => array:1 [
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                      "doi" => "10.1213/ANE.0000000000000002"
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            2 => array:3 [
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              "referencia" => array:1 [
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                            2 => "C&#46;R&#46; Roberson"
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                      "doi" => "10.1213/ane.0b013e31817b842c"
                      "Revista" => array:6 [
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            3 => array:3 [
              "identificador" => "bib0270"
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46; Wengritzky"
                            1 => "T&#46; Mettho"
                            2 => "P&#46;S&#46; Myles"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20037151"
                            "web" => "Medline"
                          ]
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            4 => array:3 [
              "identificador" => "bib0275"
              "etiqueta" => "5"
              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Odom-Forren"
                            1 => "L&#46; Jalota"
                            2 => "D&#46;K&#46; Moser"
                            3 => "T&#46;A&#46; Lennie"
                            4 => "L&#46;A&#46; Hall"
                            5 => "J&#46; Holtman"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jclinane.2013.05.008"
                      "Revista" => array:6 [
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                          0 => array:2 [
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                            "web" => "Medline"
                          ]
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                      ]
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            ]
            5 => array:3 [
              "identificador" => "bib0280"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Who is at risk for postdischarge nausea and vomiting after ambulatory surgery&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46;C&#46; Apfel"
                            1 => "B&#46;K&#46; Philip"
                            2 => "O&#46;S&#46; Cakmakkaya"
                            3 => "A&#46; Shilling"
                            4 => "Y&#46;Y&#46; Shi"
                            5 => "J&#46;B&#46; Leslie"
                          ]
                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/ALN.0b013e318267ef31"
                      "Revista" => array:6 [
                        "tituloSerie" => "Anesthesiology"
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                        "volumen" => "117"
                        "paginaInicial" => "475"
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                            "web" => "Medline"
                          ]
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              ]
            ]
            6 => array:3 [
              "identificador" => "bib0285"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk scores for predicting postoperative nausea and vomiting are clinically useful tools and should be used in every patient&#58; con &#8211; &#8216;life is really simple&#44; but we insist on making it complicated&#8217;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46;H&#46; Eberhart"
                            1 => "A&#46;M&#46; Morin"
                          ]
                        ]
                      ]
                    ]
                  ]
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Article information

ISSN: 23411929
Original language: English

DOI:10.1016/j.redare.2017.02.005

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