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Print version ISSN 0034-7094
Rev. Bras. Anestesiol. vol.57 no.4 Campinas July/Aug. 2007
The influence of epidural morphine in the pulmonary function of patients undergoing open cholecystectomy*
Influencia de la morfina peridural en la función pulmonar de pacientes sometidos a la colecistectomía abierta
Gilson Cassem Ramos, TSAI; Edísio Pereira, TSAII; Salustiano Gabriel NetoIII; Ênio Chaves de OliveiraIV; Roberto Helôu RassiV; Sílvio Pinheiro de Lemos NetoVI
e Doutor em Medicina pela UnB-DF; Responsável pelo Serviço de
Anestesia do Hospital Samaritano de Goiânia; Clínico do Hospital
da Unimed de Goiânia-GO
IIProfessor Doutor do Programa de Pós-graduação da Faculdade de Ciências da Saúde da UnB-DF
IIICirurgião do Aparelho Digestivo; Professor-Assistente de Técnica Operatória da Faculdade de Medicina da UFG-GO
IVProfessor Doutor da Disciplina de Coloproctologia da Faculdade de Medicina da UFG-GO
VPneumologista; Diretor-Geral da Clínica Pulmonar, Goiânia-GO
VIFarmacêutico-Bioquímico; Diretor Clínico do Laboratório Pinheiro-Oliveira, Goiânia-GO
OBJECTIVES: Upper abdominal surgeries may cause postoperative respiratory
dysfunction. The objective of this study was to evaluate the pulmonary function
after laparoscopic and open cholecystectomies, with and without epidural morphine.
METHODS: In this randomized, double-blind clinical trial, 45 patients undergoing cholecystectomies were divided in three groups: GL, GA, and GAM, composed of 15 patients each. The GL group underwent laparoscopic surgery, while GA and GAM underwent open cholecystectomy, but the former received epidural morphine. Pre- and postoperative spirometry and arterial blood gases were performed. ANOVA was used to verify the hypothesis of equality of the means among the groups. When results were statistically significant, the Tukey test was performed. Paired test t Student was used to verify the hypothesis of equality within a group. A p < 0.05 was considered significant.
RESULTS: The pre and immediately postoperative spirometry results were used to determine: a) forced vital capacity (FVC) in GL versus GA (p = 0.000) and GL versus GAM (p = 0.000); percentage of the reduction of FVC in GA versus GAM (p = 0.001); b) within each group: in GL, FVC (p = 0.020) and forced expiratory volume in 1 second (FEV1) (p = 0.022); in GA, FVC (p < 0.001) and FEV1 (p < 0.001); and in GAM, FVC (p = 0.007) and FEV1 (p = 0.001). The arterial oxygen pressure (PaO2) was reduced in all three groups.
CONCLUSIONS: One can conclude that respiratory dysfunction was less severe in patients operated by laparoscopy and that epidural morphine reversed, partially, the postoperative ventilatory disturbances of open cholecystectomy.
Key Words: ANALGESIA, Postoperative; epidural morphine; COMPLICATIONS, postoperative: atelectasis, diaphragmatic dysfunction; SURGERY, Abdominal: open cholecystectomy, laparoscopy cholecystectomy.
Y OBJETIVOS: Operaciones de abdomen superior pueden causar en el postoperatorio,
disfunciones de ventilación. El objetivo del presente estudio fue evaluar
la función pulmonar después de las colecistectomías laparoscópicas
y abiertas, con y sin morfina peridural.
MÉTODO: En estudio del tipo ensayo clínico doblemente encubierto y aleatorio, 45 pacientes fueron distribuidas en tres grupos, GL, GA y GAM, de 15 componentes, sometidas a colecistectomías. El grupo GL fue operado por vía laparoscópica, mientras que el GA y GAM, por vía abierta, siendo que este último recibió morfina peridural. Las pacientes realizaron espirometrías y gasometrías en el pre y en el postoperatorio. La hipótesis de igualdad de promedios entre los grupos fue verificada utilizando la ANOVA. Cuando los resultados presentaron diferencia estadística significativa, se realizaba el test de Tukey. La hipótesis de igualdad de promedios entre un mismo grupo fue verificada por medio del test t de Student conjugado. EL valor de p < 0,05 se consideró significativo.
RESULTADOS: Las variables espirométricas en el pre y en el postoperatorio inmediato: a) para capacidad vital forzada (CVF) GL versus GA (p = 0.000) y GL versus GAM (p = 0.000); para reducción porcentual de la CVF GA versus GAM (p = 0,001); b) mismos grupos entre sí: GL para CVF (p = 0,020) y volumen de expiración forzado en 1 segundo (VEF1) (p = 0,022); GA para CVF (p < 0,001) y VEF1 (p < 0,001); y GAM para CVF (p = 0,007) y VEF1 (p = 0,001). La presión arterial de oxígeno (PaO2) se redujo en todos lo grupos.
CONCLUSIONES: Podemos concluir diciendo que las menores disfunciones de ventilación se dieron en las pacientes operadas por vía laparoscópica y que la morfina peridural revistió parcialmente el disturbio de ventilación postoperatorio de colecistectomía abierta.
Pulmonary complications are the most frequent causes of postoperative morbidity and mortality. Its incidence ranges from 6 to 76% of all complications whose occurrence depends on the preoperative condition of the patient and the type of surgery 1. The postoperative period of upper abdominal surgeries lead to purely restrictive respiratory changes 2 that precede pulmonary complications 3. One observes reduction in vital forced capacity (VFC) and forced volume expired in 1 second (FEV1). A reduction in the arterial pressure of oxygen (PaO2) is also commonly seen in these cases 4. It is known that diaphragmatic dysfunction is the main mechanism related with the pathophysiology of these disturbances 5. The altered functioning of this muscle is secondary to the stimulus of reflex areas manipulated in surgical sites close to the diaphragm 6,7. Other factors that contribute and interrelate with one another and with the diaphragmatic dysfunction itself are postoperative pain, atelectasis, inhibition of mucociliary activity, duration of the surgery and tracheal intubation, and supine position during recovery 8. The objective of this study was to evaluate pulmonary function after cholecystectomies, as demonstrated by spirometry and PaO2. This study compared three groups of patients who underwent cholecystectomies and whose spirometries and PaO2 were monitored. Patients in the control group underwent laparoscopic cholecystectomy. Studies demonstrate that this surgical technique reduces the magnitude of spirometric changes and accelerates the postoperative normalization of pulmonary function 9. Patients in both study groups underwent open cholecystectomy, but one of the groups received epidural morphine.
This study was done with patients who sought the Digestive System Surgery Department of the Hospital Ortopédico de Goiânia. It was approved by the Ethics Committee on Research of the Hospital de Urgências de Goiânia and patients had to sign an informed consent.
Forty-five female patients, ages 21 to 65, with BMI equal or below 35, physical status ASA I or II, with normal preoperative exams, scheduled for cholecystectomy without intraoperative colangiography, were randomly chosen among a population of patients from the Sistema Único de Saúde (SUS). Exclusion criteria included patients using bronchodilators; smokers; those whose height could not be determined precisely (kyphoscoliosis, amputation of lower limbs, etc); pregnant women; patients with respiratory diseases, acute abdomen, past medical history of diverticulosis, duodenal ulcer, GI bleeding, neuromuscular diseases; psychiatric patients; those with contra-indications to epidural block; history of allergy to dypirone, diclofenac sodium, or to the anesthetics selected to be used in this study.
This was a double-blind clinical study for patients undergoing open cholecystectomy, and with random distribution of patients. The sample size was defined by a consensual system because it was difficult to gather the right study population. Even though the decision was consensual, 15 patients per group provide a margin of error of approximately 8%. Patients were randomly divided in three groups, each with 15 patients, and underwent cholecystectomy under epidural block plus general anesthesia. Patients in the GL group underwent laparoscopic surgery; patients in the GA group underwent open subcostal cholecystectomy through a mini-laparotomy; and patients in the GAM group followed the same protocol of the GA group but also received epidural morphine. Thus, the first, second and third patients selected for the surgical procedures were distributed, respectively, in the GL, GA, and GAM groups, and the same sequence was maintained for the remaining patients. Except by the use of epidural opioids, the anesthetic protocol was the same for all groups. The anesthetic-surgical duration was demarcated in order not to exceed one hour, including the tracheal extubation. If the procedure lasted longer than this, the patient was excluded from the protocol and a new patient was selected to complete the group.
Anesthesia was standardized in all three groups. In the operating room, each patient received initially 5 to 10 mg of intravenous diazepam after peripheral venipuncture and administration of a balanced electrolyte solution (8 mL.kg.h-1). Monitoring consisted of continuous ECG on the DII derivation, pulseoxymetry capnograph, heart rate, and blood pressure with a sphygmomanometer. The patient was placed in the left lateral decubitus. After local infiltration with 50 mg of 1% lidocaine in the L1-2 space, an epidural puncture was performed with a 16G Tuohy needle, with the bevel turned cephalad. Patients in all three groups received 93.75 mg (25 mL of local anesthetic) of 0.375% bupivacaine with adrenaline (1:200,000). Patients in groups GA and GAM received 2.0 mL of epidural normal saline and 0.03 mg.kg-1 of morphine, respectively. The level or height of the sensitive blockade promoted by the epidural anesthesia was evaluated during 20 minutes by the Hollmen criteria 10, compressing the dermatome with a non-cutting needle (40 × 8 mm). Anesthesia was induced with thionembutal (5 mg.kg-1), fentanyl (0.3 µg.kg-1) and atracurium (0.5 mg.kg-1). Patients were intubated with a 7.5 endotracheal tube and the balloon was inflated with 5 mL of air. Anesthesia was maintained with isoflurane (0.5 at 1%) and N2O in a mixture with 50% of O2. Intravenous dypirone (2 g) and intramuscular diclofenac sodium (75 mg) were administered every 6 and 12 hours, respectively, beginning when the patient was discharged from the recovery room, with a score of 10 in the Aldrete-Kroulic scale, up to 48 hours after the procedure.
Patients were always operated by the same surgeon using the same surgical technique, both for the open procedures and laparoscopies. Patients underwent serial spirometries and arterial blood gases. The first spirometry was performed preoperatively. The second, the day after the surgery, within the first 24 postoperative hours. From this moment on, new tests were performed every two days until a normal test was obtained. The same was done regarding the arterial blood gases; arterial blood was drawn from one of the radial arteries while the patient was breathing room air. Spirometries were performed by the same person, a respiratory function technician, using the same device: the portable Spiro Pro® version 2.0.
The preparation for each spirometry section was based on the norms of de Sociedade Brasileira de Pneumologia e Tisiologia 11, and included calibrating the spirometer with the proper 3 mL syringe, and adjusting it to the ambient temperature (25°C to 40°C) and atmospheric pressure (680 mmHg). Each patient performed three valid and reproducible tests. The Spiro Pro® version 2.0 uses the greatest value obtained of the equation FVC+FEV1 to select the best test result. The spirometry reports were done by the same pneumologist, a specialist in lung function testing, who interpreted the results without prior knowledge of the past medical history of the patient. The use of bronchodilators was included in the spirometries after the pulmonary technician was instructed on how to use it. However, the data obtained after the use of bronchodilators was not analyzed. The variables FVC and FEV1 were analyzed separately, considering the pre and postoperative values until they returned to normal levels (80% of the calculated value for FVC and FEV1, and around 70% for the FEV1/FVC ratio). Arterial blood gases were analyzed by a Drake AGS 21 gasometer, also manufactured in the United States, and interpreted according to the values of the PaO2 immediately after the blood was drawn.
The analysis of variance, ANOVA, was used to analyze the hypothesis of the equality of the means among the three groups. When F was significant, according to the ANOVA, multiple comparisons were made with the Tukey test. The paired test t Student was used to analyze the hypothesis of equality of the means within a group before and after the cholecystectomies. A p < 0.05 was considered significant to evaluate the differences between the parameters.
Table I shows the individual characteristics of the patients. There were no statistically significant differences.
Table II shows the mean values of FVC and FEV1, from preoperative values to the 3rd postoperative day, whose calculations were based on Table III. Statistically significant differences were detected. For FVC on the 1st postoperative day (p = 0.000), the difference was detected between the groups GL and GA, and GL and GAM; on the 3rd postoperative day, the differences were between GL and GAM (p = 0.007). As for FEV1, in the 1st (p = 0.000) and 3rd (p = 0.000) post-operative days, differences were detected between GL and GA, and GL and GAM.
Figure 1 refers to the most expressive mean reduction, in percentage, of the FVC that occurred immediately postoperatively, based on the individual analysis of each patient. In the GL, GA, and GAM groups, the reduction (mean ± standard deviation) was 7.90 ± 13.25; 35.34 ± 20.98; and 17.86 ± 21.84, respectively. Statistically significant differences were detected between the GA versus GL and GA versus GAM (p = 0.001). Figure 2 shows the evolution of the FVC, among the groups, from the preoperative period to the 3rd postoperative day.
Figure 3 demonstrates the mean values of PaO2, in mmHg, immediately pre and postoperatively. There were statistically significant differences (p = 0.011) in the preoperative period between groups GL and GA.
In the immediate postoperative period, one patient in the GL group presented a PaO2 of 64 mmHg; five patients in the GA group presented PaO2 between 32 and 78 mmHg in the immediate postoperative period and in the second post-operative day; and four patients in the GAM group developed PaO2 between 51 and 65 mmHg.
The analysis of pre and postoperative spirometry values and PaO2 by the paired test t Student demonstrated: in GL, FVC (p = 0.020); FEV1 (p = 0.022); and PaO2 (p = 306). In the GA group: FVC (p < 0.001). FEV1 (p < 0.001); and PaO2 (p = 0.298). In the GAM group: FVC (p < 0.007); FEV1 (p = 0.001); and PaO2 (p = 0.137).
Every spirometry in the GL group returned to normal values immediately after the surgery. In the GA group, 80% returned to normal in the immediate postoperative period and the remaining 20% up to the seventh postoperative day. In the GAM group, 80% returned to normal immediately after the surgery and the remaining by the third postoperative day.
In GL and GA groups, the epidural blocks stabilized between the T2 and T4 dermatomes, while in the GAM group, between T2 and T5.
Ventilatory disturbances are classified as obstructive, restrictive, and mixed 12. Isolatedly, a reduction in the FEV1/FVC ratio, or Tiffeneau index, diagnoses obstruction disturbances with certainty. Restrictive disturbances are characterized by a reduction in FVC and a normal Tiffeneau index. Mixed disturbances are more difficult to diagnose, because there is a superposition of spirometric results of obstruction and restriction (reduction of FVC and FEV1/FVC ratio). According to its severity (Table IV), respiratory disturbances can be classified as mild, moderate, and severe or accentuated, based on the results of FVC and FEV1.
This study confirmed the presence of mild restrictive ventilatory disturbances, which were more severe in the immediate postoperative period in all three groups (Table II). This result is similar to other studies 1. The GL group showed smaller spirometric changes, which has also been demonstrated by other studies 14; but in this study, the greater reduction in FVC and FEV1 in this group was 7.9% and 8.4%, respectively (Table II and Figure 1) when compared with baseline values. This means that preoperative spirometries were normal when compared to predicted values. We did not find similar reports in the literature regarding this group. There are reports demonstrating more severe changes, even in laparoscopic surgeries, with reductions between 20% and 30% 15 in both variables, and even more pronounced reductions, greater than 40% 16.
Diaphragmatic dysfunction is the main factor related with ventilatory disturbances after cholecystectomies 5,17,18, and is present even in laparoscopic surgeries. This dysfunction is not related with postoperative pain 23, lasts about one week, is mediated by inhibition reflex mechanisms of the phrenic nerve 18, and the contractility of the diaphragm is not altered 21. Another important factor in the genesis of ventilatory disturbances is postoperative pain, which contributes for the deterioration of the pulmonary function 22. Other factors are also relevant because they increase diaphragmatic dysfunction and postoperative pain, and weaken pulmonary function. They include: duration of tissue aggression (surgeries lasting more than one or two hours), the size of the incision, the damage to the muscle fibers, and tracheal intubation for more than two hours 23,24. Thus, in this study, reduced diaphragmatic dysfunction and postoperative pain, which is a characteristic of laparoscopic surgeries, associated with a shorter surgical duration, could probably explain the minimal changes in postoperative spirometries.
Ventilatory disturbances observed in patients in the GA group were more severe than in the GL group, with a significant reduction in FVC and FEV1 (p = 0.000), respectively, when compared with patients treated by laparoscopic surgeries (Table II) and similar to the results of other studies 25. The mean reduction in FVC and FEV1 in the immediate post-operative period was of 36% and 38%, respectively. The duration of the surgical procedures was similar among the three groups (less than one hour), and small incisions were performed in the open procedures. Thus, in the open procedures, the reduced length of the surgery and small incisions were not enough to cause spirometric changes similar to those obtained in laparoscopies.
The subcostal incision, near the diaphragm, is more important than the size of the incision and the length of the surgery together in the genesis of diaphragmatic dysfunction and, consequently, ventilatory disturbances. Ventilatory disturbances observed in the GAM group were less severe than those observed in other studies 26, and more severe than in the GL group. Although the presence of statistically significant differences in the immediate postoperative period in FVC between GA and GAM (Table II) were not demonstrated, we observed that the reduction of this variable was greater in the GA group (p = 0.001, Figure 1). Patients in the GAM group received a single dose of epidural morphine before anesthetic induction. This was the only intervention that differed between both groups. One can say that the analgesic effect of the opioid reduced the ventilatory disturbances. This result agrees with other studies that reported that the treatment of postoperative pain improved pulmonary function 27. Normal respiration depends, mostly, on the movements of the diaphragm and, during inspiration it exerts traction on the lower lung surface 28, making this muscle the main determinant of the FVC. Thus, diaphragmatic dysfunction is associated with a reduction in lung volumes and capacity.
It was suggested that the reflex inhibition of the phrenic nerve, whose afferent pathway originates in the sympathetic celiac plexus or another upper abdominal sympathetic ganglion, is the most important mechanism in the genesis of diaphragmatic dysfunction after abdominal surgeries 5. Besides, the stimulation of mesenteric nerves and afferent sympathetic fibers, as well as the distension of the small bowel, inhibit efferent nerve impulses of the phrenic nerve 6,7. This reflex mechanism causes diaphragmatic dysfunction and consequent postoperative restrictive ventilatory disturbances in laparoscopic cholecystectomies 19. This finding is related to the site of the surgery. The area of the laparoscopic cholecystectomy includes afferent visceral pathways of the mesenteric region, which are reflexive and weaken the diaphragmatic function 6,7. Since the stimulus at the site of the laparoscopic cholecystectomy is weaker than in the open procedure, the answer of the reflexive pathways will be weaker, explaining the smaller change in function and faster recovery of spirometric values in these procedures, similar to the findings of our study.
The length of time for the return of spirometric values to baseline was not an objective of this study, but their normalization according to predicted values. Other studies reported that the recovery in pulmonary function after upper abdominal surgical procedures varies from seven to 14 days 8, and during this period, the individual is more vulnerable to pulmonary complications 3. Every patient in the GL group had normal spirometries in the immediate postoperative period, but they were inferior to preoperative values. In this group, the spirometric values decreased from preoperative parameters in the immediate postoperative period, but in the following testing (3rd postoperative day) they had returned to baseline values.
Some studies reported that it takes from eight to ten days for a full recovery of the pulmonary function after laparoscopic cholecystectomy 22, which was not the case in the current study. This difference may be justified by the reduced duration of the surgery, with less tissue damage and reduced diaphragmatic dysfunction in the patients in the GL group. The spirometries of patients in GA and GAM groups normalized on the 7th and 3rd postoperative day, respectively.
One may consider that the analgesia provided by epidural morphine seem to have reduced the normalization period (Figure 2) of postoperative spirometries, which should be confirmed in a study with a larger number of patients. The postoperative evolution of FVC and FEV1 was more favorable in the patients in the GL group, followed by the GAM group and then the GA group. This result relative to the GL group, better than in similar observations, can be explained by the laparoscopic technique associated with a short surgical duration.
Likewise, regarding patients in the GAM group, although their spirometric parameters were inferior to the GL group, the effects of epidural morphine eased the reduction of FVC and FEV1 when compared with the GA group, whose patients did not receive the opioid, with consequent delay in the normalization of those parameters. FVC is the main respiratory parameter to detect restrictive ventilatory disturbances. In this study, the mean of this variable indicated mild postoperative disturbances, although some patients presented severe disturbances. For example, a patient in the GA group presented a reduction of approximately 92% in FVC in the 1st postoperative day (Table II, order 12, group GA). Two patients in the GAM group developed 51% and 65% reduction. This indicates the potential risk of postoperative complications patients are subjected to, including acute respiratory failure and death 24,29.
Postoperative gas exchange follows two temporal patterns 4. Patients develop hypoxia immediately after the procedure, which can persist for approximately two hours. During this phase, the reduction in PaO2 is related with the general anesthesia (alveolar hypoventilation, ventilation-perfusion mismatch, and reduced cardiac output) rather than with changes in lung mechanics.
On the other hand, the second pattern is more closely related with the surgical procedure itself, when the capacity of the patient to take deep breaths is reduced or the patient is restricted to bed. During this phase, the patient has hypoxemia without hypercarbia 4. There is an important association between the reduction in PaO2 and the reduction in functional residual capacity (FRC) and the relationship between this last parameter and the airways closure capacity 30. The O2 used to supply the tissues is found in the FRC. The FRC is reduced after upper abdominal surgeries, and can remain so for two weeks 31. This reduction, getting closer to the airways closing capacity, can promote closure of small airways even during normal breathing, predisposing to hypoxemia 32. This is the main cause of late hypoxemia after upper abdominal surgeries, followed by atelectasis, which are common in the postoperative period of this type of procedure, and correlate with reduction in spirometric variables 33.
In this study, there was a statistically significant difference in preoperative PaO2 between GL and GA groups (p = 0.011), but it did not have any clinical implication, i.e., it was not accompanied by hypoxemia. Every blood sample was drawn at the same time spirometries were done. Although mean blood gas values remained within normal limits, PaO2 showed a reduction in all groups (Figure 3), with the presence of hypoxemia in some patients in all three groups. This reduction, which happened at the same time as the most pronounced reduction in spirometric variables, agrees with the results of other authors 34 and can be explained by the probable fall in FRC 35. The overall absence of hypoxemia, without statistically significant differences, can be justified by the reduced duration of the procedure and of tracheal intubation, which reduces the formation of atelectasis, therefore reducing the incidence of hypoxemia.
Some authors reported that pulmonary complications, with formation of atelectasis 36, are related with a long surgical duration. Surgeries lasting less than one hour, from one to two hours, from two to four hours, and lasting more than four hours, presented 4%, 23%, 38%, and 73% of pulmonary complications, respectively. Likewise, general anesthesia with tracheal intubation for more than two hours, also had a greater incidence of postoperative complications 24,29.
Epidural block, for the peritoneal or visceral (gallbladder, for examples) region, becomes an auxiliary anesthetic technique, since a significant amount of the innervation of the gallbladder and bile ducts originates from the hepatic plexus 37, which is not reached by the epidural block. Thus, general anesthesia is indicated and the epidural block is complementary, with an important postoperative analgesic function. Therefore, it is necessary that the epidural block reach a level superior to that of the surgical region, and this objective was achieved in this study.
The subcostal incision for open cholecystectomy is made at the level of the T9 dermatome. In this study, every epidural block was above this region. This study confirmed the results of other studies 38 about the superiority of laparoscopy for cholecystectomies regarding pulmonary function. However, in Brazil, a large number of open cholecystectomies is performed. According to the DataSUS (www.datasus.gov. br), 92% of the cholecystectomies performed in patients of the SUS during 2004 used the open technique. There are several reasons to explain these results: lack of financial resources to purchase and maintain the laparoscopic equipment, the large number of older surgeons who do not have experience with most modern techniques, and the teaching of surgical residents. Besides, there are contraindications related to the patient, such as complicated cholelithiasis, severe cardiac or cardiorespiratory disease, and anatomical abnormalities of the abdominal wall or cavity caused, by example, by previous abdominal surgeries.
Morphine binds to specific opioid receptors (mu-1), promoting active spinal analgesia. The duration of action of a single dose in the epidural space may last up to 24 hours 39, the period in which the pain is more severe. Only a very small fraction of morphine reaches its site of action when administered systemically. This is secondary to its low liposolubility. For this reason, its systemic efficacy is much lower than when it is administered epidurally 40.
The clinical impression is that pain is relevant in the etiology of postoperative ventilatory changes, since upper abdominal surgeries usually evolve with severe postoperative pain 41.
Thus, this study demonstrated that a single dose of epidural morphine can be an adjuvant alternative to reduce the presence of restrictive ventilatory disturbances, which invariably occur in the postoperative period of open cholecystectomies. In this study, it decreased the magnitude of postoperative ventilatory disturbances and the epidural administration tends to shorten the duration of the postoperative respiratory disturbance, which can reduce pulmonary morbidity and mortality. It is obvious that the continuous observation of respiratory function is necessary to prevent the most important side effect, although rare in the doses preconized in clinical practice: respiratory depression.
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Dr. Gilson Cassem Ramos
Rua 8, 74/402 Setor Oeste
74115-100 Goiânia, GO
Submitted em 1
de setembro de 2006
Accepted para publicação em 26 de abril de 2007
* Received from Serviço de Anestesia do Hospital Samaritano de Goiânia, GO e do Programa de Pós-Graduação em Ciências da Saúde da UnB-DF