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On-line version ISSN 1806-907X
Rev. Bras. Anestesiol. vol.55 no.5 Campinas Sept./Oct. 2005
Postoperative nausea and vomiting: a review of the "minor-major" problem*
Náuseas y vómitos en el posoperatorio: una revisión del "pequeño-grande'' problema
Neusa Lages, M.D.I; Cristina Fonseca, M.D.I; Aida Neves, M.D.II; Nuno Landeiro, M.D.II; Fernando José Abelha, M.D.II
IInterno Complementar de Anestesiologia
IIAssistente Hospitalar Graduado
BACKGROUND AND OBJECTIVES: Notwithstanding
continuous investigations and the development of new drugs and techniques, postoperative
nausea and vomiting (PONV) are frequent and may contribute to the development
of complications, thus increasing hospital and human costs. This article aimed
at reviewing physiological mechanisms, risk factors and therapeutic approaches
available to manage PONV.
CONTENTS: Several strategies to manage PONV are suggested in this article, but stress is given to guidelines published by Gan in 2003. They are the most recent contribution for risk stratification, prevention and treatment of PONV patients.
CONCLUSIONS: Although the management of PONV has improved in recent years, it is still common among high-risk patients. Current strategy to prevent and treat PONV is not yet established and Gan guidelines should be adapted to each population and institution.
Key Words: ANTIEMETICS; COMPLICATIONS: postoperative nausea, vomiting
JUSTIFICATIVA Y OBJETIVOS: A pesar de
la averiguación continuada y del desarrollo de nuevos fármacos y técnicas,
las náuseas y vómitos en el posoperatorio (NVPO) son frecuentes y
pueden aportar para el desarrollo de complicaciones con consecuente aumento
de los costeos hospitalarios y de los recursos humanos. Los objetivos de este
artículo son la revisión de los mecanismos fisiológicos, de los
factores de riesgo y las medidas terapéuticas disponibles para el manoseo
CONTENIDO: Varias son las estrategias de manoseo de NVPO sugeridas en este artículo, destacándose, sin embargo, las líneas de orientación emitidas por Gan en 2003. Éstas, constituyen la contribución más reciente para la estratificación del riesgo, prevención y tratamiento de los pacientes con NVPO.
CONCLUSIONES: Aunque el manoseo del NVPO haya mejorado en los últimos años, éstos aún ocurren frecuentemente en grupos de riesgo elevado. La estrategia actual para la prevención y manoseo de NVPO permanece por establecer y las líneas de orientación de Gan deberán ser adaptadas a cada población de pacientes y a la institución hospitalaria.
Postoperative nausea and vomiting (PONV) are among most frequent complications during anesthetic recovery. Until 1960, when inhalational anesthetics such as ether or cyclopropane were widely used, the incidence of vomiting could reach 60% 1. Today, in spite of the progress of anesthetic techniques, of short-lasting drugs and of the development of new antiemetic drugs, global incidence is still approximately 20% to 30% 2. Pediatric patients are not spared and children above 3 years of age have an incidence of PONV of approximately 40% 3. In risk populations, PONV may reach 70% and approximately 0.2% of patients may suffer untreatable PONV 2, delaying hospital discharge, requiring unexpected admissions, generating a low level of patients' satisfaction and increasing hospital costs. In addition to above-mentioned complications, more severe situations may be generated, such as suture dehiscence, vomiting aspiration, aspiration pneumonia, dehydration, hydroelectrolytic changes, esophageal rupture and increased intracranial pressure.
Several studies were carried out to determine major postoperative concerns. Eberhart et al. have evaluated 220 patients and have stratified which of the 9 proposed scenarios (from 81 possible) for the recovery unit would be more desirable to be avoided. PONV was the scenario most patients would like to avoid (49%), followed by others such as pain (27%) and no sedation (13%) 5. Eberhart et al. have concluded that patients would be willing to accept other complications and even additional personal costs to minimize or prevent PONV. Macario et al. in a similar study have proposed to patients to spend a hypothetical amount of 100 dollars to prevent some anesthetic side effects 6. The conclusion was that patients would be willing to spend a higher amount to prevent vomiting (18 dollars) and nausea (12 dollars), as compared to preventing postoperative pain (17 dollars) or shivering (8 dollars). Gan et al., in a different study, has also concluded that patients were willing to spend more than 100 dollars, at their own expenses, for an effective antiemetic drug 7.
PONV DEFINITIONS AND PHYSIOLOGY
Nausea and vomiting are not synonyms, being important to separate them since some drugs are more effective against nausea and others against vomiting 8. Nausea is the uncomfortable sensation associated to the need for vomiting, while vomiting is the forced expelling of gastric content.
The act of vomiting is controlled by the vomiting center, located in the lateral reticular formation of the spinal cord. It receives afferences from the chemoreceptor zone (4th ventricle floor), vestibular tract, cerebellum, solitary tract nucleus and upper cortical centers. There are several receptors involved in transmitting impulses to the vomiting center: muscarinic, dopaminergics (D2), hystaminergics (H1), opioids, serotoninergics (5-HT3) and neurokyninics (NK-1) 9. Vomiting pathways may be triggered by several stimulations that integrate and activate the vomiting center. Other factors also contribute for PONV, such as dehydration, some odors, pain, concern and fear 9. Mechanisms of action of antiemetics and receptors blockade or stimulations already mentioned are represented in figure 1.
IDENTIFICATION OF PONV RISK FACTORS
Several studies have been carried out to identify PONV risk factors and anticipate patients with higher risk of this complication 2,10-12. These may be related to patients, surgical procedure or anesthetic technique.
Patient-related factors are gender, age, previous PONV history, motion sickness and smoking. Males seem to be more protected against PONV, with one third lower incidence as compared to females 2,12. Age above 18 years is considered by some studies as protective against PONV, while others do not confirm it 2,11,12.
Some studies attribute a protecting effect to previous smoking history 2,11-13. Some surgical procedures are traditionally associated to higher incidence of PONV (strabismus correction, ENT surgery, gynecologic surgery, shoulder surgery and laparoscopic surgery) 12. In a recent study with approximately 5200 patients, the relative risk was similar for all types of surgery, when corrected for Apfel's risk factors, except for hysterectomies and possibly laparoscopic cholecystectomy 13. So, predictive models of PONV risk including surgery type do no add to predictive value as compared to simplified models 14,15. Surgery length and surgeon's experiences (associated to the intensity of visceral manipulation) are also considered risk factors 16.
Anesthesia-related factors influence the incidence of PONV 16. Hypotension, especially during induction, postoperative opioids and ineffective analgesia contribute to a higher incidence of PONV. Three meta-analysis have shown that lack of N2O decreases PONV in adults submitted to low risk procedures 8. Proposed mechanism consists of N2O spread to middle ear with vestibular tract stimulation, and to the bowel distending it, inducing spinal cord dopaminergic system activation and increasing endogenous opioids in CSF. Other authors advocate that lack of N2O is correlated to the use of higher oxygen concentrations and that this would be the protecting mechanism 17. High doses of anticholinesterase drugs used to antagonize neuromuscular block increase gastric motility and PONV 18. Inhalational anesthesia is also of higher risk as compared to total intravenous anesthesia, especially in terms of early PONV 19.
Considering that several factors influence PONV genesis and worsening, many attempts have been made to obtain predictive factors and identify patients at high risk for PONV. Sinclair et al. have developed a mathematical model to anticipate PONV risk in ambulatory patients 12. Participated in this prospective study 17,638 ambulatory patients of whom 816 (< 5%) have developed PONV. Predictive factors identified were: age, gender, and history of smoking, history of PONV, type of anesthesia and surgery type and length. Koivuranta et al. have concluded in a prospective study with 1107 patients aged 4 to 86 years, that predictive factors for PONV would be female gender, previous PONV history, surgery length, history of smoking and history of motion sickeness 11.
There are several studies on the subject, but the most popular predictive model is the model developed by Apfel et al. 19. This model is based on 4 risk factors: female gender, history of motion sickness and/or history of PONV, no smoking and postoperative opioids. The incidence of PONV would be 10%, 21%, 61% and 79%, respectively, whether 1, 2, 3 or 4 factors are present (Table I).
Apfel's predictive scores are easy to apply, with reasonable predictability of PONV; in addition, they allow for the comparison among several groups in the domain of clinical antiemetic investigations. Some authors have criticized Apfel for the difficulty in applying some of his risk factors 20, especially how to classify occasional smokers, how to consider patients without surgical history and how to anticipate the prescription of postoperative opioids. In spite of all limitations, risk scores help clinicians define the group of patients benefiting of preventive therapy.
In the early 2003, a multidisciplinary group of experts has met to create recommendations for adults and children, based on exhaustive literature review, for the managing of PONV and the definition of risk groups 21. Chart I shows risk factors for adults and children.
PONV PREVENTION AND TREATMENT
Several questions are posed when the issue PONV prevention versus treatment is addressed. Should we prevent it, or should we wait for its development and then treat. If PONV is preventively treated which drugs or doses should be used? If deciding for a conservative approach and treating after the development of PONV, which drugs or doses should be used? If patients are preventively treated and even then develop PONV, which drugs or doses should be used?
With preventive treatment, many patients at low risk for PONV will be unnecessarily treated, in addition to being exposed to the adverse effects of drugs, while other patients will present PONV despite of the treatment. Routine antiemetics are associated to high costs, which in a time of costs and resources contention should be avoided. However, preventive antiemetics in moderate to high-risk patients have an effective cost-benefit ratio and are associated to higher level of patients' satisfaction 22.
The 2003 consensus conference has recommended preventive treatment for patients at moderate to high risk of PONV or for those with potential morbidity associated to PONV, specifically suture dehiscence, esophageal rupture, hematoma and aspiration pneumonia 21. Whenever possible, it is recommended to identify risk factors and minimize them. Visser et al. have shown that propofol for anesthetic induction and maintenance decreases the incidence of early PONV (first 6 postoperative hours) 23. The incidence of PONV decreases when inhalational anesthetics or nitrous oxide are avoided 24. Neostigmine in doses equal to or below 2.5 mg decreases PONV 18. Sinclair et al. has shown that loco-regional anesthesia decreases PONV risk 11 times as compared to general anesthesia 12. Yogendran et al. has concluded that effective fluid therapy with blood pressure maintenance during induction decreases the incidence of PONV 25.
High perioperative oxygen inspired fractions decreases in 50% the incidence of nausea and vomiting 26. Last but not least, less opioids and effective analgesia (surgical wound infiltration with local anesthetics or cycloxygenase inhibitor administration) also contribute to decrease the incidence of nausea and vomiting 26.
ANTIEMETIC DRUGS USED FOR PONV PREVENTIVE TREATMENT (Table II)
Serotonin receptor antagonists: there is no difference in efficacy and safety profile within this group of drugs - ondansetron, dolasetron, granisetron or etropisetron 21. These are more effective when administered at surgery completion and are more useful to prevent vomiting as compared to nausea 27,28.
Dexamethasone: the action mechanism of steroids as antiemetic drugs is still to be explained. They are more effective when administered before anesthetic induction. Most popular intravenous dose is 8 to 10 mg, but lower doses (2.5 to 5 mg) are also effective. Notwithstanding side effects of these drugs, such as surgical wound infection or adrenal gland suppression, no side effects were observed after bolus doses 29.
Droperidol: is one of the most widely studied antiemetics to prevent PONV and is similar in efficacy to ondansetron 30. It is better to prevent nausea than to prevent vomiting and is more effective when administered at surgery completion 31. In morphine patient-controlled analgesia this seems to be the most effective antiemetic drug. Doses between 15 and 50 µg droperidol per mg of morphine are those with best efficacy/side effects ratio 32. In 2001, the Food and Drug Administration has published a warning about the association of droperidol in patients with prolonged QT interval at ECG and/or Torsade de Pointes, which in some cases has resulted in arrhythmias and death.
This warning was based on 10 clinical cases observed along 30 years of clinical use, in which doses equal to or below 1.25 mg were used 33. As a consequence, the laboratory producing droperidol has recommended ECG monitoring during and 2 to 3 hours after its administration and has counterindicated it for male patients with QT intervals above 440 ms or for female patients with QT intervals above 450 ms. Other risk patients are those with congestive heart failure, bradycardia, ventricular hypertrophy, hypokalemia, hypomagnesemia, patients medicated with diuretics or other drugs which may originate prolonged QT interval. Some droperidol advocates argue that there are no descriptions in indexed publications of clinical cases in which prolonged QT interval, arrhythmias or death were associated to droperidol in adequate doses to prevent PONV.
Other antiemetic drugs: subcutaneous scopolamine should be administered the night before surgery or approximately 4 hours before surgery completion 34. It is not recommended for the elderly and its limitation is late onset (2 to 4 hours after administration) 35. Phenothyazides (prometazine and proclhorperazine) are effective if administered at surgery completion, but their adverse effects (sedation, dizziness and dehydration) limit its use, especially in outpatient regimen 36. Intramuscular ephedrine seems to be effective, especially if nausea and vomiting are associated to dehydration or hypotension 37.
Non-pharmacological techniques: acupuncture, compression, intradermal nervous stimulation and hypnosis were effective if used before surgery 38, but they lack further evaluation.
Insufficient Evidences: intravenous metoclopramide in doses used in the clinical practice (10 mg) is not recommended to treat PONV 39, as well as ginger root 40 or cannabinoids 41.
A multimodal antiemetic approach has been recommended in recent years, based on the multifactorial concept of PONV etiology. So, using more than one class of antiemetics it would be possible to reach more than one receptor involved in PONV.
The already mentioned consensus conference has recommended no preventive treatment for low risk patients; for moderate risk patients, prevention with single or combined therapy; for high risk patients, prevention with 3 antiemetic drugs of different classes 21. However, a recent study has stressed that the combination of different therapies is associated to higher costs, higher risk of side effects and lack of cumulative benefit of several antiemetic drugs. For these authors, combined therapy should be kept for patients at high risk for PONV or those who may be at risk due to PONV 42. This specific group has a higher number of candidates to antiemetic prevention, since the incidence of PONV is two-fold. First line drugs should be 5-HT3 receptor antagonists. Due to its extra-pyramidal effects, droperidol should be kept for admitted children when all other therapies have failed 21.
Guidelines for the treatment of PONV of patients who have not received preventive treatment or those for whom prevention has failed (Chart II) 21.
First, all drugs or mechanical factors that may originate PONV should be withdrawn and then treatment should be started.
Patients not receiving preventive PONV treatment should be given 5-HT3 antagonists. One fourth of preventive doses have shown to be effective. There are still few data on doses and efficacy of other antiemetics to treat PONV. In patients with failed preventive treatment, low 5-HT3 receptor antagonist doses are recommended.
If prevention with 5-HT3 receptor antagonists has failed, subsequent doses of the same class of drugs should not be used during the first 6 postoperative hours. If prevention with 5-HT3 receptor antagonists associated to dexamethasone was ineffective, a different class of antiemetics should be administered.
In general, patients with PONV in the first 6 postoperative hours should be treated with different classes of antiemetics than those used for prevention. If PONV is present 6 hours after surgery, drugs used for prevention may be repeated, with the exception of scopolamine or dexamethasone, because they act for more than 6 hours.
Low propofol doses may be used, provided patients are under continuous surveillance.
Although PONV management has improved in recent years, it is still frequent in high-risk groups.
The identification of risk factors for PONV, frequently done during preoperative evaluation, helps preventive therapy. The publication in 2003 of international recommendations for PONV management allowed the definition of patients benefiting from single, double or triple therapy as a function of identified risk level.
From different available drugs, droperidol, 5HT3 receptor antagonists and dexamethasone play a distinctive role in controlling PONV, and their association, based on action mechanisms and efficacy/tolerance ratio, has allowed for more effective PONV control.
Notwithstanding limited data in the literature and variations in the identification of risk factors, recommendations for adults are extrapolated to children. It should be reminded that these recommendations do not rule out the individualized analysis and its adaptation to populations, surgical and anesthetic techniques.
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Dr. Fernando José Abelha
Hospital São João
Address: Al. Professor Hernâni Monteiro
ZIP: 4100 319 City: Porto, Portugal
Submitted for publication March 15, 2005
Accepted for publication May 31, 2005
* Received from Departamento de Anestesiologia e Cuidados Intensivos, Hospital São João, Porto, Portugal