Anesth Pain Med 2014; 9: 222-227 ￭Clinical Research￭
Palonosetron for postoperative nausea and vomiting after gynecological laparoscopic surgery: Comparison of its effect on sevoflurane vs desflurane vs total intravenous anesthesia
† Department of Anesthesiology and Pain Medicine, *Chosun University School of Medicine, Chosun University Hospital, Gwangju, Korea
Ki-tae Jung*,†, Kyung-Joon Lim*,†, Hyo-sung Bae†, Dong-won Jo†, and Hyun-Young Lee*,†
Background: Postoperative nausea and vomiting (PONV) is one of the most common complications after gynecological laparoscopic surgery and it appears more frequently after use of inhalation INTRODUCTION anesthetics than total intravenous anesthesia (TIVA). Palonosetron was introduced as a new-generation potent antiemetic agent, which Postoperative nausea and vomiting (PONV) is one of the may reduce PONV more effectively than previous drugs. The aim most common complications following surgery [1]. PONV of this study was to evaluate whether palonosetron could prevent occurs on an average, in 20 to 30% of patients who have PONV after gynecological laparoscopic surgery, regardless of the anesthetic technique employed. undergone surgery with general anesthesia, and the incidence Methods: Seventy-three patients scheduled for gynecological increases up to 70% in high risk patients within 24 hr after laparoscopic surgery were randomly assigned into 3 groups emergence [1,2]. PONV increases patient morbidity by according to the anesthetic agent employed (group 1: inhalation increasing the frequency of adverse post-operative events such anesthesia with desflurane, group 2: inhalation anesthesia with sevoflurane, group 3: total intravenous anesthesia with propofol and as bleeding, pulmonary aspiration, wound dehiscence, or remifentanil). Palonosetron 0.075 mg was administered intrave- delayed discharge [2]. According to previous reports, risk nously before the induction. Opioids were not used for postoperative factors such as gender, personal history of PONV, smoking, pain control. The incidences of nausea, vomiting and side effects use of opioids, characteristics of surgery, laparoscopic surgery, were recorded from 2 hr upto 48 hr, postoperatively. Results: There were no significant differences in the incidence of and anesthetic agent are closely related to the incidence of PONV, severity of nausea, and the use of rescue antiemetics among PONV [1-5]. The incidence of PONV has been reported as the groups, throughout the observation. No differences were high as 75%, without prophylactic antiemetic drugs [5] and up observed in the adverse side effects among the groups. to 70% with prophylactic antiemetic drugs after laparoscopic Conclusions: Palonosetron decreased the incidence of PONV after gynecological laparoscopic surgery to a similar level, gynecological surgery [6]. regardless of the anesthetic technique. (Anesth Pain Med 2014; Recent studies have shown that the prevalence of PONV, 9: 222-227) differs depending on the anesthetic methods or agents [2,4,5,7]. Key Words: Gynecological surgery, Inhalation anesthesia, In general, total intravenous anesthesia (TIVA) is known to Intravenous anesthesia, Laparoscopy, Palonosetron, reduce the PONV due to the antiemetic effect of propofol, as Postoperative nausea and vomiting. compared to inhalation anesthesia [8].
Palonosetron, a selective 5-HT3 receptor antagonist, is a potent antiemetic with a high receptor affinity and a long duration of action [9,10]. It was reported that palonosetron was more effective in preventing PONV after gynecological Received: February 25, 2014. laparoscopic surgery than ondansetron [11], and was also more Revised: March 10, 2014. Accepted: March 28, 2014. effective in reducing the incidence of vomiting during the first Corresponding author: Kyung-Joon Lim, M.D., Department of Anesthe- 6 hr post-surgery [6]. Thus, we hypothesized that the strong siology and Pain Medicine, Chosun University School of Medicine, 365, antiemetic effect of palonosetron could reduce the difference of Pilmun-daero, Dong-gu, Gwangju 501-717, Korea. Tel: 82-62-220-3223, Fax: 82-62-223-2333, E-mail: [email protected] PONV after inhalation anesthesia vs. TIVA in the patients who
222 Ki-tae Jung, et al：Effect of palonosetron and anesthetics 223 have undergone gynecological laparoscopic surgery. Moreover, intravenously for the induction of anesthesia in the patients from there are no reports on the comparative antiemetic effects of groups 1 and 2. After endotracheal intubation, anesthesia was palonosetron according to the anesthetic agents and methods. maintained with inhalation anesthetic agents and 50% oxygen-air In this study, we compared the antiemetic effects of mixture; desflurane 6 vol% in the group 1 and sevoflurane 2 palonosetron in patients who were subjected to general vol% in the group 2. TIVA, with propofol and remifentanil was anesthesia with sevoflurane vs. desflurane vs. TIVA with used for both, the induction and maintenance of anesthesia in the propofol and remifentanil, for gynecological laparoscopic group 3. Minto and Marsh pharmacokinetic models were applied Ⓡ surgery. by a TCI device (Orchestra Base Primea, Fresenius-Vial, France). Targeted effect-site concentrations of propofol and MATERIALS AND METHODS remifentanil for induction were 3 g/ml and 2.5 ng/ml for the induction, respectively. The minimum alveolar concentration and This study was approved by the Hospital’s Institutional the targeted effect-site concentrations were adjusted to maintain Review Board. Female patients who were scheduled to undergo anesthetic depth within the range of 40–60 of BIS score and vital gynecological laparoscopic surgery such as hysterectomy or signs within a 20% range of the baseline. At the end of surgery, oophorectomy were included in this study. The subjects of this reversal agents (pyridostigmine 0.15 mg/kg with glycopyrrolate study were aged between 18 years and 64 years, had 0.006 mg/kg) were administered. Patients were transferred to the American Society of Anesthesiologists physical status I or II, recovery room after confirmation of adequate respiratory effort. and were non-smokers with no history of PONV or motion Patient-controlled analgesia (PCA) and opioids were not used for sickness. Patients with the following conditions were excluded: the postoperative pain control, according to the policy of the pregnancy; previous nausea or vomiting attributed to gynecologic department, instead only nonsteroidal anti-inflam- gastrointestinal disease, chemotherapy, or radiation therapy; matory drugs (NSAIDs) were used. Metoclopramide 10 mg was treatment with antiemetics within 3 days before surgery; QTc administered intravenously as a rescue antiemetic drug, when prolongation in electrocardiogram; inability to answer the moderate to severe PONV (more than the visual analogue scale question correctly because of dementia or cerebrovascular [VAS] score 5) had occurred, or on patient request. disorder; or allergic reaction to the drugs of the study. The age, height, weight, BMI, duration of anesthesia, and The purpose and the method of this study were explained duration and type of surgery were recorded. Parameters of and written consent was obtained from each patient. Patients PONV were assessed and recorded at each time interval i.e. 0– were randomly divided into three groups according to the 2 hr, 2–24 hr, and 24–48 hr from the time moved to the anesthetic agents, by computerized random number generation. recovery room, until complete wakefulness. by doctors who In the group 1 (desflurane group), inhalation anesthesia was had not participated in the anesthesia. The frequencies of maintained with desflurane and 50% oxygen-air mixture, nausea, vomiting, and the use of antiemetic drug were likewise when sevoflurane was used in the group 2 measured. The severity of PONV was measured by the VAS (sevoflurane group). In the group 3 (TIVA group), propofol score (0–10 scale; 0, no nausea; 10, worst nausea). Adverse and remifentanil were used for TIVA. All patients were effects such as headache, dizziness and abdominal discomfort premedicated with midazolam 0.05 mg/kg about 30 minutes were recorded during study. After 48 hrs from the end of before anesthesia. anesthesia, overall patient satisfaction was assessed on a When patients arrived at the operation room, basic three-point scale (satisfied, neutral, and dissatisfied). monitoring devices (Anesthetic Monitoring System S/5TM, Data were expressed as mean ± standard deviation or number Datex-Ohmeda Inc., Helsinki, Finland.) were attached to the (%) of patients. Windows version 12.0, SPSS Inc., (Chicago, IL, patients. Electrocardiogram, pulse oximetry, end tidal carbon USA) software was used for the data analysis. Chi-square or dioxide monitor, non-invasive arterial pressure, the bispectral Fisher’s exact tests were performed for the comparison of index (BIS) (BIS monitor A-2000; Aspect Medical Systems, categorical variables. ANOVA and Kruskal-Wallis test were Norwood, MA, USA) were monitored during anesthesia. performed to evaluate the statistical significance between the Palonosetron 0.075 mg was administered intravenously before groups. Post hoc analysis was done with Bonferroni’s correction the induction. After preoxygenation with 100% O2 for 3 minutes, and values with P ＜ 0.05 were considered statistically signi- propofol 2 mg/kg and rocuronium 1.0 mg/kg were administered ficant. 224 Anesth Pain Med Vol. 9, No. 3, 2014
Table 1. Demographic Data
Group 1 (Desflurane) Group 2 (Sevoflurane) Group 3 (TIVA) (n = 24) (n = 24) (n = 25)
Age (yr) 43.2 ± 9.8 43.8 ± 6.5 40.7 ± 8.5 ASA class 1 18 (75.0) 20 (83.3) 20 (80.0) 2 6 (25.0) 4 (16.7) 5 (20.0) Height (cm) 157.75 ± 6.0 158.4 ± 4.8 158.2 ± 3.5 Weight (kg) 60.6 ± 9.5 57.6 ± 6.0 55.0 ± 5.4 BMI 24.4 ± 4.1 23.0 ± 2.4 22.0 ± 2.1 Duration of surgery (min) 62.3 ± 27.4 63.3 ± 29.0 61.2 ± 275.4 Duration of anesthesia (min) 75.0 ± 24.7 78.1 ± 26.6 76.2 ± 24.0 Type of surgery Hysterectomy 12 (50.0) 13 (54.2) 13 (52.0) Oophorectomy 12 (50.0) 11 (45.8) 12 (48.0)
Data presented as mean ± SD or n (%) of patients. ASA: American Society of Anesthesiologists.
Table 2. Incidence of Postoperative Nausea and Vomiting, Severity of Nausea, and Need for Rescue Antiemetics
Group 1 (Desflurane) Group 2 (Sevoflurane) Group 3 (TIVA) (n = 24) (n = 24) (n = 25)
0–2 hr Nausea 10 (41.7) 11 (45.8) 8 (32.0) Vomiting 4 (16.7) 4 (16.7) 2 (8.0) Severity of nausea 3.4 ± 1.5 3.5 ± 1.9 2.7 ± 1.5 Rescue antiemetics 10 11 8 2–24 hr Nausea 6 (25.0) 6 (25.0) 2 (8.0) Vomiting 1 (4.2) 1 (4.2) 0 (0.0) Severity of nausea 4.3 ± 3.0 3.2 ± 1.9 1.5 ± 0.7 Rescue antiemetics 5 6 1 24–48 hr Nausea 3 (12.5) 3 (12.5) 2 (8.0) Vomiting 0 0 0 Severity of nausea 1.7 ± 1.2 1.7 ± 0.6 2.0 ± 1.4 Rescue antiemetics 1 2 1
Data presented as mean ± SD or n (%) of patients. Severity of nausea was assessed with visual analogue scale from 0 to 10. 0: no nausea, 10: worst nausea.
RESULTS Table 3. Incidence of Complications and Patient Satisfaction Group 1 Group 2 Group 3 A total of 75 patients were recruited and 73 patients were (Desflurane) (Sevoflurane) (TIVA) enrolled. One patient was excluded because of secondary (n = 24) (n = 24) (n = 25) operation due to postoperative bleeding in group 1. The other Headache 4 (17) 3 (13) 5 (20) patient was excluded because the surgeon had changed the Dizziness 0 (0) 1 (4) 0 (0) operative plan to laparotomy during laparoscopic surgery. Abdominal discomfort 8 (23) 7 (29) 5 (20) There were no significant differences in demographic data, Patient satisfaction Satisfied 19 (79) 18 (75) 18 (72) duration and type of surgery, and duration of anesthesia, Neutral 2 (8) 4 (17) 7 (28) between the groups (Table 1). There were no statistical Dissatisfied 3 (13) 2 (8) 0 differences in the incidence of PONV, severity of nausea, and Data presented as n (%) of patients. the intravenous use of rescue antiemetics among the three groups during the 2 hr time interval, 2–24 hour time interval, Ki-tae Jung, et al：Effect of palonosetron and anesthetics 225 and 24–48 hour time interval post-surgery. (Table 2). There group administered TIVA, compared to a group administered were also no significant differences in the incidence of adverse sevoflurane. TIVA prevented early PONV in patients effects and the overall patients’ satisfaction score among the undergoing gynecological laparoscopic surgery [5]. Contrarily, three groups (Table 3). inhalation anesthetics are known to act as pro-emetic agents and thus caused the early vomiting [15]. Sevoflurane and DISCUSSION desflurane have similar potencies in producing PONV [16]. However, inhalation anesthetics are not the most important In this study, we evaluated the effects of palonosetron risk factor of PONV, and antiemetics are effective in according to the anesthetic agents and methods employed. prophylaxis of PONV independent of risk factors, including After use of palonosetron, there were no statistical differences volatile anesthetics [17]. The effectiveness of palonosetron in in the incidence of PONV, severity of nausea, and the use of preventing PONV was not previously evaluated. Thus, we rescue antiemetics between the groups 1 (desflurane group), 2 conducted the current study to evaluate the comparative (sevoflurane group) and 3 (TIVA group). combinatorial effectiveness of palonosetron according to the PONV is still a major complaint after surgery and the mode of anesthesia i.e. desflurane, sevoflurane or TIVA. incidence is as high as 40–75% after laparoscopy [5,12]. Besides, Palonosetron, a ‘second- generation’ of 5-HT3 receptor PONV is extremely unpleasant with a subjective feeling of poor antagonists has unique properties including a higher affinity to patient satisfaction and high disagreeability after emergence. the receptor and a much longer half-life that allows for a Thus, management of PONV is as important as that of pain. As prolonged duration of action [18]. Prophylactic palonosetron mentioned earlier, the incidence of PONV is closely related to 0.075 mg, was more effective than other 5-HT3 receptor risk factors [1-3,13], with a high risk associated with the female antagonists in preventing PONV [11,18,19]. It was also sex, a history of PONV or motion sickness, non-smoker, opioids, significantly effective in decreasing the incidence and severity volatile agents, nitrous oxide, long surgical procedures, and major of nausea in the early recovery period [18]. Early PONV is gynecological surgery, or laparoscopic surgery [1,3,13]. It is still generally regarded as a result of residual volatile anesthetics not fully understood why gynecological laparoscopic surgery [5]. Thus, we hypothesized that the palonosetron, a potent increases the risk of PONV. Residual pneumoperitoneum after antiemetic with a high receptor affinity and effectiveness in artificial insufflation with CO2 and positional changes, and phase prevention of early PONV, can reduce the difference of of menstrual cycle are suspected to be attributing factors [12]. incidence of PONV after anesthesia with inhalation anesthetics The patients in this study had two risk factors of Apfel score vs. TIVA with propofol and remifentanil. (female and non-smoker) [1,3] and underwent gynecological In this study, there was no significant difference in the laparoscopic surgery [1,13]; therefore, a high incidence of PONV incidence and severity of PONV between the group using was expected after surgery. TIVA and the groups using inhalation anesthetics, throughout The incidence of PONV after anesthesia depends on the the observation period. Importantly, palonosetron effectively anesthetic agents and methods. Tramer et al. [14] had decreased the incidence and severity of nausea during the conducted a meta-analysis of prophylactic antiemetic effects of initial 2 hr after emergence. In the previous report, the anesthetic regimens. They reported that the use of propofol incidence of PONV 24 hr after gynecological laparoscopic decreased the incidence of early nausea and vomiting and surgery with no antiemetic prophylaxis were 75 and 15.8% maintenance of anesthesia with propofol showed favorable when sevoflurane and TIVA were used for anesthesia, effects by decreasing late PONV, compared to inhalation respectively [5]. However, in this study the incidence of anesthesia. Another study similarly reported the antiemetic nausea according to anesthetic technique i.e. inhalation vs. effect of propofol and TIVA. TIVA with propofol had a TIVA had decreased during 2 hr post-surgery. The incidences clinically relevant reduction of PONV compared with were 41.7%, 45.8%, and 32.0% in the desflurane, sevoflurane, isoflurane-nitrous oxide anesthesia [8]. These results indicate and TIVA groups, respectively. Our findings were similar to a that propofol has a strong antiemetic effect and maintenance of previous report that, palonosetron is significantly effective in anesthesia with propofol has the added advantage of preventing decreasing the incidence and severity of nausea in the early PONV consistently [1,8,13,14]. Recently, a study showed that period [18]. It appears to be effective in decreasing the PONV the incidence of PONV was significantly lower in a patient associated with residual volatile anesthetics in groups 1 and 2. 226 Anesth Pain Med Vol. 9, No. 3, 2014
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