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Table of Contents
Year : 2021  |  Volume : 5  |  Issue : 2  |  Page : 61-65

Comparison between target-controlled infusion propofol and target-controlled inhalational anesthesia sevoflurane in mastectomy surgery in Indonesia

Department of Anesthesiology and Intensive Care, Faculty of Medicine, Udayana University, Bali, Indonesia

Date of Submission06-Aug-2020
Date of Decision02-Jan-2021
Date of Acceptance13-Jan-2021
Date of Web Publication16-Apr-2021

Correspondence Address:
Dr. I Gusti Ngurah Mahaalit Aribawa
Department of Anesthesiology and Intensive Care, Faculty of Medicine, Udayana University, Jl. PB Sudirman, Denpasar 80232, Bali
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/BJOA.BJOA_178_20

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Background: Health-care system reform in Indonesia is challenging for anesthesiologists in determining the minimum cost of anesthesia and maintaining inflammation and pain to a minimum. This study is aimed to analyze the effectiveness of general anesthesia techniques between target-controlled inhalational anesthesia (TCIA) sevoflurane and target-controlled infusion (TCI) propofol in mastectomy surgery from the perspective of cost, C-reactive protein (CRP) levels, postoperative pain level, postoperative opioid consumption, and side effects. Patients and Methods: This was a randomized controlled trial with permuted block randomization of 60 subjects allocated into TCIA sevoflurane (Group S) and TCI propofol (Group P). In Group S, we used sevoflurane 8 vol% for induction and maintained with sevoflurane 1–1.5 vol%, compressed air, and oxygen. In Group P, we used TCI propofol with target effect 4 mcg/mL and maintained with TCI propofol (target effect of 1–3 mcg/ml), compressed air, and oxygen. Results: The cost in Group S was US$ 36.33 compared to US$ 29.69 in Group P (P = 0.002). The CRP level was comparable between the two groups (38.39 [42.13] vs. 23.88 [45.26]. P = 0.487). There is neither difference in pain score, total morphine consumption, and side effects between both groups in the first 24-h postoperative period, nor morphine consumption in 24 h postoperative. Conclusion: The cost of anesthesia-related expense in TCI propofol is lower than TCIA sevoflurane in mastectomy surgery underwent general anesthesia. There is no significant difference in terms of CRP levels, postoperative pain, postoperative morphine consumption, and incidence of side effects.

Keywords: C-reactive protein, inflammation, morphine consumption, pain, side effect

How to cite this article:
Mahaalit Aribawa I G, Agung Senapathi TG, Gede Widnyana I M, Utara Hartawan I G, Pradana AP, Ryalino C. Comparison between target-controlled infusion propofol and target-controlled inhalational anesthesia sevoflurane in mastectomy surgery in Indonesia. Bali J Anaesthesiol 2021;5:61-5

How to cite this URL:
Mahaalit Aribawa I G, Agung Senapathi TG, Gede Widnyana I M, Utara Hartawan I G, Pradana AP, Ryalino C. Comparison between target-controlled infusion propofol and target-controlled inhalational anesthesia sevoflurane in mastectomy surgery in Indonesia. Bali J Anaesthesiol [serial online] 2021 [cited 2022 Aug 18];5:61-5. Available from: https://www.bjoaonline.com/text.asp?2021/5/2/61/313876

  Introduction Top

Sevoflurane is a fluorinated, methyl isopropyl ether with a blood-gas partition coefficient of 0.69, which theoretically possible to provide induction of anesthesia shortly and gain consciousness rapidly after it was stopped.[1],[2],[3] Target-controlled inhalational anesthesia (TCIA) is a technique in which anesthesiologists will adjust the volatile agent's concentration to achieve the desired target level, based on the end-tidal (ET) of the anesthetic agent concentration and the level of consciousness according to the bispectral index (BIS). Newer machines are created with automatic semi-closed or closed breathing circuit technology to control the ET levels of volatile anesthetic agents, oxygen, and nitrous oxide (N2O).[4],[5],[6]

On the other hand, target-controlled infusion (TCI) propofol system maintains the desired target concentration and could be tailored to the patient clinical requirements. TCI would be set into specific concentration to be achieved and maintained by plasma concentration (Cp) and effect-site concentration (Ce) based on the level of consciousness, according to BIS.[7]

Healthcare reform in Indonesia, marked by the implementation of the state-run health insurance, is increasingly challenging for anesthesiologists to reduce the cost of general anesthesia, especially to determine the cost-effectiveness of the latest anesthesia techniques, drugs and technologies without affecting inflammation, pain level, opioid consumption, and side effect. The total expense of general anesthesia has become a problem in the hospital's management.[8],[9],[10]

This study was performed to analyze the effectiveness of general anesthesia techniques between TCIA sevoflurane and TCI propofol in mastectomy surgery in the perspective of the cost of anesthesia, 24-h postoperative C-reactive protein (CRP) levels, postoperative pain scores, postoperative opioid consumption, and side effects.

  Patients and Methods Top

This study was a randomized controlled trial. Subjects were patients who underwent mastectomy surgery in Sanglah General Hospital, who met the eligibility criteria. All subjects provided written informed consent to participate in this study. The study was approved by the institutional ethics committee (registry number 1408/UN.14.2/KEP/2016) registered on 05/06/2016.

The inclusion criteria include patients with the American Society of Anesthesiologists Physical Status I or II. Aged 16–64 years, height ≥130 cm, body mass index of 18.5–24.5 kg/m2, and agreed to participate in this study by signing the informed consent form. Exclusion criteria include intraoperative bleeding of >30% of the estimated blood volume, allergic to propofol or sevoflurane, psychiatric disorders, neurologic deficits, and those with a history of cardiac or cerebrovascular events.

This study employed permuted block randomization, where 60 subjects were allocated into TCIA sevoflurane (Group S) and TCI propofol groups (Group P), each consisted of 30 subjects [Figure 1]. Before starting anesthesia in all patients in both groups, 3 mL of the venous blood sample was withdrawn for CRP examination. All patients received intravenous (IV) midazolam 0.05 mg/kg at 15 min before induction as premedication and fentanyl 2 mcg/kg. In Group S. We administered sevoflurane 8% in N2O and oxygen mixture (at 2:1 comparison) until BIS value reached 40–60. In Group P, we used TCI propofol (Schneider mode) with target-effect concentration (Ce) of 4 mcg/mL until the BIS value indicates 40–60. We used atracurium 0.5 mg/kg as a muscle relaxant in both groups. After endotracheal intubation, the fresh gas flow (FGF) was set with compressed air 0.5 L/min and oxygen 0.5 L/min. Volume-controlled ventilation mode was set to maintain end-tidal CO2 at 35–40 mmHg. Sevoflurane in Group S was set to maintain ET sevoflurane concentration to 1%-1.5% and BIS index 40–60. The target Ce of propofol in Group P was set to 1–3 mcg/ml. During surgery, BIS value was maintained at 40–60 by adjusting the target Ce of propofol by 0.5 mcg/ml incremental titration.
Figure 1: The CONSORT flow diagram

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Postoperative analgesics were administered with IV morphine patient-controlled analgesia (PCA). The total cost for general anesthesia for both groups was calculated after surgery and converted to US$ from local currency (US$ 1 = Rp. 15.000). CRP level 24 h postoperatively was checked. We used VAS to assess pain level at 1 h, 3 h, 6 h, and 24 h postsurgery and monitor the side effects that may occur. The PCA unit records demand, delivery, and total morphine consumption.

We used the Statistical Package for Social Sciences (SPSS) software (IBM Corp. Released 2017. IBM SPSS Statistics for Windows. Version 25.0. Armonk. NY: IBM Corp.) as a data analysis tool. Data were presented accordingly as mean and standard deviation, median and interquartile range, or proportion. We used the unpaired t-test to see if the groups were comparable. We then employed the Mann–Whitney U-test and Chi-square test to test our hypotheses. A P < 0.05 was considered significant.

  Results Top

There were 60 subjects enrolled in this study and they were divided equally into both groups. Both groups were normally distributed, as shown in [Table 1]. We also found no significant difference between the two groups in surgery duration (P = 0.607), duration of anesthesia (P = 0.718), and the total intraoperative dose of fentanyl (P = 0.653).
Table 1: Characteristics of the study groups

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The cost analysis comparison between the two groups [Table 2] obtained a significant difference (US$ 36.33 vs. US$ 29.69, P = 0.002). The difference of CRP levels [Table 3] in both groups was insignificant at an hour before the surgery (P = 0.773) and 24-h postoperatively (P = 0.492). We assessed the postoperative pain level using VAS. We found that the VAS level between the two groups were insignificant at 1-h postoperative (P = 0.887), 3 h (P = 0.908), 6 h (P = 0.686), and 24-h (P = 0.674). The 24-h total morphine consumption was 6.90 ± 4.83 mg in Group S compared to Group P's 4.96 ± 4.02 mg (P = 0.113).
Table 2: Anaesthesia-related cost comparison between the two groups

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Table 3: Comparison of C-reactive protein, postoperative pain level, and total postoperative morphine consumption

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We observed the incidence of several side effects, including agitation, vomiting, nausea, coughing, bronchospasms, and tachycardia. Nausea and vomiting occurred in eight patients in Group S and four patients in Group P. No other side effects were reported in this study [Table 4].
Table 4: Incidence of side effects

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  Discussion Top

This study used an advanced anesthesia station which implements the target system controlled inhalational anesthesia. The station adjusts the levels of anesthetic agents to achieve the target level desired by the anesthetist. It automatically controls the ET level of volatile anesthetics, oxygen, and N2O. This would create a revamp in the consumption of volatile anesthetics and FGF. It also allows for less usage of inhaled agents per unit time.

We also used a BIS monitor to assess the depth of anesthesia. It captures the frontal section of the EEG brain wave. When patients begin to lose consciousness, the BIS index value begins to decrease <70. BIS monitor reduces the dose of anesthetic drug usage by up to 30%.

In this study, we used low FGF (1 L/min) for sevoflurane as many studies revealed that it is safe to use low flow FGF with sevoflurane, despite the concern of the compound-A that is not proven to harm the human kidney.[11],[12] The fentanyl requirements did not differ significantly between the two groups due to its synergistic effect with sevoflurane and propofol.

We compared the costs of general anesthesia using TCIA sevoflurane to TCI propofol. The cost includes medications administrated as premedication, hypnotic, muscle relaxant, analgesics, maintenance during surgery, and treatment of side effects. Many studies showed that TCI propofol is significantly more expensive than inhalational anesthesia.[12],[13],[14],[15],[16],[17] However, some of those studies only compared the cost of sevoflurane and propofol used for induction and maintenance of anesthesia,[15.16] while this study calculated all drugs for perioperative anesthesia.

Our study found that TCI propofol is cheaper than TCIA sevoflurane, with a significant difference. Differences with previous research are likely due to differences in how costs were calculated, as well as the price difference of the sevoflurane and propofol. A similar study reported in 2016 at the same hospital obtained different results.[18] Nowadays, the price of propofol in Indonesia is currently about 20%–25% compared to 2016, which is before the era of obligatory governmental insurance.

The tools used to measure the hypnotic effect was the BIS index monitor, which has been approved by the Food and Drugs Administration, to monitor the depth of anesthesia. The cost analysis does not include costs of N2O, O2, and disposable material (i.e., nasal cannula, infusion sets, IV catheter, and gloves). Salaries for anesthesia staffs (anesthetist, nurses, and other assistants) are also not included in this study. The main reason for excluding those components was to be able to identify the cost of the anesthesia drugs used in TCIA sevoflurane and TCI propofol.

In previous studies, propofol showed an anti-inflammatory property by reducing the increase of postoperative CRP level.[19],[20] Another study reported a significant increase in CRP level in propofol compared to sevoflurane.[9] We found no significant differences in postoperative CRP level between the two groups. The discrepancy may occur due to different details and protocols used in general anesthesia. One study was carried out in continuous propofol for sedation after surgery in the intensive care unit where sevoflurane was only given intraoperatively.[19] Another study used TIVA propofol rather than TCI propofol, and the depth of anesthesia was not monitored by BIS.[9]

Our study found no significant difference between the postoperative pain level and total postoperative morphine consumption between the two groups. These results are in line with previous studies.[21],[22] However, other studies reported propofol better reduced postoperative pain and consumption of postoperative opioids.[23],[24]

In clinical practice, the severity of acute postoperative pain depends on many factors. In animal studies, it was reported that propofol exerts analgesia and anti-hyperalgesia effects (by the activation of GABA receptors) and reduces response from dorsal horn to nociception stimuli, blocked the phosphorylation of subunit receptor N-methyl-D-aspartate receptors (NR1), and the CB1–CB2 cannabinoids.[25],[26] Nevertheless, this effect will be diminished in humans soon after propofol administration is stopped.

Total morphine consumption between the two groups in our study did not differ significantly, which is similar to previous publications,[21],[22] although several studies reported lower opioid consumption in the propofol group compared to inhalational anesthesia.[23],[24],[27] The discrepancy may result due to the use of combined multimodal analgesics, such as dexmedetomidine, dexamethasone, and remifentanil. Those agents strengthen the analgesic property of propofol.[24],[27]

The side effects that occurred most in this study were postoperative nausea and vomiting (PONV). PONV mostly occurs in general anesthesia, especially in cases where an inhalational agent was administrated. The TCIA technique composed a controlled dose of sevoflurane, therefore minimizing the risk of PONV.

  Conclusion Top

The cost of anesthesia-related expense in TCI propofol is lower than TCIA sevoflurane in mastectomy surgery underwent general anesthesia. There is no significant difference in terms of CRP levels, postoperative pain, postoperative morphine consumption, and incidence of side effects.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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  [Figure 1]

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

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