Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 3  |  Page : 343-348

The effects of coinduction with sevoflurane–propofol and sevoflurane–ketofol in patients undergoing radiofrequency ablation of hepatocellular carcinoma


Department of Anesthesiology and Intensive Care, Ain-Shams University, Cairo, Egypt

Date of Submission01-Jul-2015
Date of Acceptance14-Jul-2015
Date of Web Publication31-Aug-2016

Correspondence Address:
Rania M Ali
Department of Anesthesiology and Intensive Care, Ain-Shams University, Cairo
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.189095

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  Abstract 

Background
Radiofrequency ablation (RFA) is a minimally invasive and effective method for local tumor destruction in nonsurgical patients with early-stage hepatocellular carcinoma (HCC). General anesthesia (GA) has been used for RFA. GA can decrease the hepatic blood flow and cause more hepatic dysfunction. This study aimed to compare the hemodynamic response, recovery characteristics, and postprocedural analgesia after induction of GA with either sevoflurane–propofol or sevoflurane–ketofol in liver patients undergoing RFA of HCC.
Patients and methods
Eighty patients with hepatic cirrhosis scheduled for RFA of HCC were randomly allocated into two groups. In group PS, induction of anesthesia was achieved using sevoflurane with propofol (1%). In group KPS, induction of anesthesia was achieved using sevoflurane with ketofol (prepared at a ratio of 1: 2).
Results
Regarding the induction time, the laryngeal mask airway (LMA) insertion time, the percentage of LMA insertions from the first attempt, time to removal of LMA, and time to emergence were comparable between the two groups. However, the rescue analgesia time was longer in group KPS compared with group PS (P < 0.001). The number of episodes during which blood pressure was below 20% of baseline blood pressure, as well as the highest and the lowest mean arterial pressure, was comparable between the two groups. Postoperative levels of liver enzymes were comparable between the two groups. In the recovery unit, only one patient (2.5%) in group KPS suffered from postoperative emergence agitation, and three patients (7.5%) suffered from nausea.
Conclusion
Either sevoflurane–propofol or sevoflurane–ketofol may be used as alternatives in liver patients undergoing RFA of HCC as both techniques have favorable anesthetic profiles and provide hemodynamic stability. However, when choosing sevoflurane–ketofol, the advantage of its enhanced analgesic effect must be weighed against the increased risk for postoperative nausea and vomiting.

Keywords: hepatocellular carcinoma, ketofol, propofol, radiofrequency ablation, sevoflurane


How to cite this article:
Ali RM, Khairy MA. The effects of coinduction with sevoflurane–propofol and sevoflurane–ketofol in patients undergoing radiofrequency ablation of hepatocellular carcinoma. Ain-Shams J Anaesthesiol 2016;9:343-8

How to cite this URL:
Ali RM, Khairy MA. The effects of coinduction with sevoflurane–propofol and sevoflurane–ketofol in patients undergoing radiofrequency ablation of hepatocellular carcinoma. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Apr 11];9:343-8. Available from: http://www.asja.eg.net/text.asp?2016/9/3/343/189095


  Introduction Top


Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Egypt has the highest prevalence of hepatitis C virus in the world and the prevalence of HCC has been increasing over the last few years [1]. Ultrasound-guided radiofrequency ablation (RFA) is a minimally invasive and effective method for local tumor destruction in nonsurgical patients with early-stage HCC [2].

RFA is a long and painful procedure for the patient, especially when there is more than one nodule and when the nodule's location is subcapsular [2]. General anesthesia (GA) has been used for RFA as it achieves better pain control compared with conscious sedation with local anesthetic techniques [3]. However, HCC is usually associated with liver cirrhosis or chronic hepatitis; thus, most patients with HCC are complex and there is little evidence to favor any particular choice of anesthetic agent [4].

GA can decrease the hepatic blood flow by 40% in the first 30 min of anesthesia induction, especially when blood pressure is not maintained at baseline levels [5]. In patients with hepatic dysfunction, especially cirrhosis cases, compensation for reduced portal blood flow does not occur under anesthesia [6]. This may cause more hepatic dysfunction, difficulty in anesthesia management, and postoperative loss of consciousness [7].

Volatile induction and maintenance of anesthesia with sevoflurane provides greater cardiovascular stability than target-controlled infusion of propofol [8],[9],[10] and less reduction in left ventricular mechanical performance [11]. However, for day-case surgery, sevoflurane is associated with significantly more postoperative nausea and vomiting (PONV) [12],[13],[14]. It was also found that, although less costly than total intravenous anesthesia (TIVA), the total cost per episode for volatile induction and maintenance of anesthesia was greater than that of propofol induction with volatile maintenance.

Coinduction with sevoflurane–propofol has been shown to optimize the insertion conditions of the laryngeal mask airway (LMA) and decrease the side effects that may follow either sevoflurane or propofol alone [15],[16]. Our hypothesis is that coinduction of anesthesia with sevoflurane–ketofol would have the same advantages as it has not been investigated yet.

To the best of our knowledge very little is known in the scientific literature about anesthetic techniques for RFA of HCC. The aim of the current study was to compare the hemodynamic response, recovery characteristics, and postprocedural analgesia after induction of GA with either sevoflurane–propofol or sevoflurane–ketofol in liver patients undergoing RFA of HCC.


  Patients and methods Top


After approval of the research ethical committee of the Faculty of Medicine, Ain Shams University, and provision of written informed patient consent, 80 patients with hepatic cirrhosis (Child scores A and B) of both sexes aged 20–60 years who were scheduled for RFA of HCC in Ain Shams University Hospitals were included in the study conducted from January 2014 to November 2014.

Exclusion criteria included presence of ascites, history of hepatic encephalopathy, altered mental status, hepatic lesions greater than 5 cm, or more than three lesions, known allergy to drugs used in the study, increased risk for aspiration, or uncontrolled cardiovascular, pulmonary, or renal dysfunction.

Patients were divided into two groups using a computer-generated random numbers table:

Group PS (n = 40): Induction of anesthesia was achieved using sevoflurane with propofol (20-ml syringe containing propofol 1% at 10 mg/ml).

Group KPS (n = 40): Induction of anesthesia was achieved using sevoflurane with ketofol [prepared at a ratio of 1: 2 as follows: 20-ml syringe containing ketamine 1 ml (50 mg), propofol 1% 10 ml (100 mg), and normal saline 9 ml]. The concentrations of these drugs were thus 2.5 mg/ml ketamine and 5 mg/ml propofol.

Preoperatively, we evaluated the serum levels of liver enzymes [aspartate aminotransferase, alanine aminotransferase, serum albumin (Alb), total bilirubin, serum creatinine, and serum sodium (Na)], in addition to complete blood count, international normalized ratio, and hepatitis screening. If the platelets were below 50 000 cells/mm3, 6 U of platelets were infused before the procedure, and fresh frozen plasma was infused as indicated.

On arrival at the operating room in the interventional radiology unit, a peripheral intravenous cannula was inserted and Ringer's lactated solution was infused. Patients were monitored using ECG, noninvasive automated arterial blood pressure monitor, pulse oximetry, and capnography.

After preoxygenation, fentanyl 1 mg/kg was administered slowly intravenously. Anesthesia was induced with a single vital capacity breath of sevoflurane 8% [17] along with 0.1 ml/kg intravenous of the study solution. Once the eyelash reflex was lost, the patients received 0.1 mg/kg atracurium. Sixty seconds later an LMA of appropriate size was inserted following the standard technique by an anesthesiologist who was blinded to the study. Effective ventilation was confirmed by capnograph trace. After successful LMA insertion, anesthesia was maintained with sevoflurane 2% and O2: air 40: 60. Patients were ventilated with the synchronized intermittent mandatory ventilation mode to maintain ETCO2 within 35–40 mmHg. At the completion of surgery sevoflurane was discontinued. The LMA was removed when the patients displayed a regular respiratory pattern but were still nonresponsive to stimulation. After achieving adequate spontaneous breathing, purposeful movement of all extremities, and eye opening, the patients were transferred to the recovery unit. After fulfilling an Aldrete score of at least 9 [18], patients were discharged from the postanesthesia care unit to an intermediate care unit for 24 h.

In the operating room (OR), the following time intervals and variables were evaluated and recorded for all patients:

  1. Time of the procedure.
  2. Time of anesthesia (from the start of induction to end of surgery, which coincides with discontinuation of sevoflurane).
  3. Induction time (from the start of induction to loss of eyelash reflex).
  4. LMA insertion time (from loss of eyelash reflex to LMA insertion).
  5. LMA insertion from the first attempt.
  6. Time to removal of LMA (from the end of anesthesia to removal of LMA).
  7. Time of emergence (time to first response to a simple verbal command following discontinuation of sevoflurane).
  8. Mean arterial pressure (MAP) and heart rate, measured before anesthesia induction and considered as baseline value and then every minute for 30 min after insertion of LMA followed by every 5 min until discharge from the OR to the recovery unit. The number of episodes during which blood pressure was below 20% of baseline blood pressure was recorded. The lowest MAP was also recorded. Hypotension was treated by the administration of intravenous fluids and ephedrine increments (5–10 mg bolus of intravenous ephedrine, according to the degree of hypotension, was administered. The second dose was repeated after 5 min if the blood pressure was not normalized).


In the recovery unit and the intermediate care, the following time intervals and variables were evaluated and recorded for all patients:

  1. Incidence of hallucinations and PONV were recorded.
  2. Rescue analgesia time [time from LMA removal to the first complaint of pain visual analogue scale (VAS)³4 necessitating the need for rescue analgesia]. Pain (VAS³4) was treated with intravenous acetaminophen 10 mg/ml.
  3. Liver enzyme levels and functions were measured 24 h postoperatively.


Statistical analysis

PASS 11 was used for sample size calculation

Power calculations were based on former studies. Group sample sizes of 35 patients per group achieve 80% power to detect a difference of 10.0 mmHg in blood pressure assuming that the group means are 90.0 and 80.0 with estimated group SDs of 20.0 and with a significance level (α) of 0.05000 using a two-sided two-sample t-test. To compensate for dropouts and missing data the sample size was increased to 40 patients per group.

Statistical analysis was performed using a standard SPSS software package, version 17 (SPSS Inc., Chicago, Illinois, USA). Data were presented as mean ± SD values, n (%), or median (interquartile range). Student's t-test was used to analyze the parametric data, and categorical variables were analyzed using the χ2-test. Nonparametric data were compared using the Mann–Whitney test. P values less than 0.05 were considered statistically significant.


  Results Top


There was no significant difference between the two groups as regards age, sex, weight, and mean duration of procedure or anesthetic time [Table 1].
Table 1 Demographic data, duration of the procedure, and duration of anesthesia

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Regarding induction time, patients in group KPS lost verbal contact later compared with patients in group PS, but there was no statistically significant difference between the two groups. Similarly, the LMA insertion time and the percentage of LMA insertions from the first attempt were comparable between the two groups. There was no significance difference between the two groups as regards time to removal of LMA or time of emergence. Regarding the rescue analgesia time, there was a statistically significant difference between the two groups as patients requested analgesia earlier in the PS group [Table 2].
Table 2 Anesthetic and analgesic outcome

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The number of episodes during which blood pressure was below 20% of baseline blood pressure, as well as the highest and the lowest MAP, was comparable between the two groups [Table 3].
Table 3 Changes in the mean arterial pressure throughout the procedure

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Preoperative liver enzyme, alanine aminotransferase, and aspartate aminotransferase levels were comparable in the two groups. Although postoperative liver enzyme levels showed a statistically significant increase compared with baseline values in both groups, they were comparable between the two groups. Serum albumin, total bilirubin, platelet count, and international normalized ratio were comparable between the two groups [Table 4].
Table 4 Preoperative and postoperative laboratory findings

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In the recovery unit, only one patient (2.5%) in group KPS suffered from postoperative emergence agitation, and three patients (7.5%) suffered from nausea.


  Discussion Top


The current study demonstrated that both sevoflurane–propofol and sevoflurane–ketofol when used for induction of GA in patients undergoing RFA of HCC provided stable hemodynamic parameters as well as good induction and recovery characteristics. Further, although sevoflurane–ketofol had an enhanced analgesic effect, it was associated with increased risk for PONV.

RFA is a novel minimally invasive technique of tumor destruction by heat in hepatic malignancies. In the RFA procedure, puncture and passing of the electrical current are painful. It was found that, even with appropriate conscious sedation with local anesthesia techniques, patients experience pain during ablation procedures [19],[20]. GA has been used for RFA as it achieves better pain control compared with local anesthesia [3]. It was demonstrated that performing RFA with GA can decrease the number of sessions required to achieve complete tumor ablation in HCC patients and shorten the hospitalization duration [21]. Simultaneously, treatment of HCC by RFA under GA is associated with reduced risk for cancer recurrence. This is in contrast to studies on other types of cancer, which have found lower recurrence rates when cancer surgery is performed using regional anesthesia. One theory is that GA affects the immune system, allowing otherwise dormant cancer cells to progress into clinical disease. Further, the minimally invasive RFA procedure has less effect on the immune system compared with surgery, and the effect of anesthesia on HCC recurrence differs from that for other cancers [22]. Accordingly, in the current study, GA was chosen as the modality of anesthesia for patients undergoing RFA of HCC.

Anesthesia in patients with cirrhosis and liver disorders is a challenging issue doubled by the presence of HCC. Patients with liver disease are more likely to have hepatic decompensation with the use of anesthesia. GA reduces total hepatic blood flow, especially the contribution of the hepatic artery. Patients with liver disease tend to have several baseline cardiovascular abnormalities, including decreased systemic vascular resistance and increased cardiac index, which may further affect the hepatic blood flow. In addition, catecholamine and other neurohormonal responses are impaired in patients with liver disease; therefore, intraoperative hypotension may not trigger adequate compensatory mechanisms [23].

There is little evidence to favor any particular choice of anesthetic agent. All volatile anesthetics decrease the MAP and portal blood flow. Sevoflurane has been consistently shown to better preserve hepatic blood flow and function [24]. Intravenous anesthetics have a modest impact on hepatic blood flow, and no meaningful adverse impact on postoperative liver function if the MAP is adequately maintained throughout the duration of anesthesia. Induction agents such as ketamine have little impact on the hepatic blood flow. It also increases heart rate and blood pressure by activating the sympathetic nervous system [25]. Despite its obvious advantages, ketamine alone can cause emesis, and recovery agitation, and has a prolonged recovery time [26]. Propofol increases the total hepatic blood flow in both hepatic arterial and portal venous circulation, suggesting a significant vasodilator effect [27],[28]. The elimination kinetic profile of propofol is similar in cirrhotic patients as well as in normal patients, but the mean clinical recovery times may be longer after prolonged infusions [29]. Accordingly, propofol has been recommended for anesthesia in patients with cirrhosis [24]. However, sensitivity to the sedative and cardiorespiratory depressant effects of propofol are increased in liver patients; hence, it should be used cautiously [24].

The combination of ketamine and propofol ‘ketofol’ has been studied as an agent for procedural sedation and analgesia in the emergency department [30],[31],[32], for endobronchial ultrasound-guided needle aspiration [33], colonoscopy [34], minor orthopedic surgeries [35], for transrectal ultrasound-guided prostate biopsy [36], for electroconvulsive therapy [37], and in pediatric patients under lumbar puncture or bone marrow aspiration [38]. The anesthesia profiles of ketofol have been evaluated for GA in pediatric patients [39],[40] and in adult elective operations under GA as well [41],[42],[43]. Administering ketofol has been shown to be efficacious, with a low incidence of postoperative emergence phenomenon and postoperative vomiting and less hemodynamic instability. However, there are no data on the anesthetic profile of ‘ketofol’ in hepatic RFA settings.

Inhalational induction remained largely confined to pediatrics and to the management of difficult airways [44]. When propofol or ketofol is used alone for induction, a high dose is needed to improve the LMA insertion conditions. Coinduction with sevoflurane–propofol has the advantage of rapid induction and hemodynamic stability [15],[16],[17]. Further, coinduction with sevoflurane–ketofol has not been investigated yet.

The result of the current study showed that both the induction and recovery characteristics and also the hemodynamic parameters were comparable between the two groups. These finding could be explained by the supplementation of sevoflurane with a small dose of either propofol or ketamine.

Another finding in the current study regarding the rescue analgesia time is that patients requested analgesia earlier in the sevoflurane–propofol group. This was mostly because of the additional use of ketamine in the sevoflurane–ketofol group, which provides an analgesic component that is absent when propofol is used alone.

The result of the current study also showed no significant difference between the two groups in terms of liver enzyme levels and functions. These parameters may have to be measured together with the coagulation profile at longer intervals postoperatively to obtain a significant result. As patients with pre-existing cirrhosis who develop postoperative liver failure usually start to show symptoms and signs around 72 h after surgery, developing jaundice, encephalopathy, and coagulopathy [45], the current study showed that only one patient (2.5%) in group KPS suffered from postoperative emergence agitation, and three patients (7.5%) suffered from nausea. These adverse effects might be reduced in the PS group because of the presence of propofol as it has intrinsic antiemetic properties that may persist into the postprocedural period [33]. Another explanation may be that both sevoflurane and ketamine cause frequent PONV.

As RFA of HCC is usually performed on an outpatient basis, the type of anesthesia must be chosen carefully to avoid delayed discharge.


  Conclusion Top


Either sevoflurane–propofol or sevoflurane–ketofol might be used as alternatives in liver patients undergoing RFA of HCC, as both techniques have favorable anesthetic profiles and provide hemodynamic stability. However, when choosing sevoflurane–ketofol, the advantage of its enhanced analgesic effect must be weighed against the increased risk for PONV.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4]


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