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Cost Minimization Analysis of Hypnotic Drug: Target Controlled Inhalation

Anesthesia (TCIA) Sevoflurane and Target Controlled Infusion (TCI) Propofol

Article · September 2016

DOI: 10.15562/bmj.v5i3.300

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 Bali Medical Journal (Bali Med J) 2016, Volume 5, Number 3: 51-56
P-ISSN.2089-1180, E-ISSN.2302-2914

Cost Minimization Analysis of Hypnotic Drug: Target Controlled Inhalation Anesthesia (TCIA)
Sevoflurane and Target Controlled Infusion (TCI) Propofol

Made Wiryana1, I Gusti Ngurah Mahaalit Aribawa2*, Tjokorda Gde Agung Senapathi3, I Made
Gede Widnyana4, I Gusti Agung Gede Utara Hartawan5, Made Agus Kresna Sucandra6,
Pontisomaya Parami7, Kadek Agus Heryana Putra8, IB Krisna Jaya Sutawan9, IGNA Putra
Arimbawa10, Ketut Semara Jaya11, Gede Semarawima12

1
Professor, 2-10Lecturer, 11Head of Medical Service Division, 12Resident
Anesthesiology and Intensive Care Department, Udayana University,
Sanglah General Hospital, Denpasar, Bali, Indonesia
*Corresponding: Email: mahaalit@unud.ac.id

Background: Cost minimization analysis is a pharmaco-economic study used to compare two or more
health interventions that have been shown to have the same effect, similar or equivalent. With limited
health insurance budget from the Indonesian National Social Security System implementation in 2015,
the quality control and the drug cost are two important things that need to be focused. The application
of pharmaco-economic study results in the selection and use of drugs more effectively and efficiently.
Objective: To determine cost minimization analysis of hypnotic drug between a target controlled
inhalation anesthesia (TCIA) sevoflurane and a target controlled infusion (TCI) propofol in patients
underwent a major oncologic surgery in Sanglah General Hospital. Methods: Sixty ASA physical status
I-II patients underwent major oncologic surgery were divided into two groups. Group A was using
TCIA sevoflurane and group B using TCI propofol. Bispectral index monitor (BIS index) was used to
evaluate the depth of anesthesia. The statistical tests used are the Shapiro-Wilk test, Lavene test, Mann-
Whitney U test and unpaired t-test (α = 0.05). The data analysis used the Statistical Package for Social
Sciences (SPSS) for Windows. Results: In this study, the rate of drug used per unit time in group A
was 0.12 ml sevoflurane per minute (± 0.03) and the group B was 7.25 mg propofol per minute (±0.98).
Total cost of hypnotic drug in group A was IDR598.43 (IQR 112.47) per minute, in group B was
IDR703.27 (IQR 156.73) per minute (p>0.05). Conclusions: There was no statistically significant
difference from the analysis of the drug cost minimization hypnotic drug in a major oncologic surgery
using TCIA sevoflurane and TCI propofol.

Keywords: Hypnotic drug, cost minimization analysis, TCIA sevoflurane, TCI propofol

http://dx.doi.org/10.15562/bmj.v5i3.300

Cite This Article: Wiryana, M., Aribawa, I., Senapathi, T., Widnyana, I., Hartawan, I., Sucandra, M.,
Parami, P., Heryana Putra, K., Sutawan, I., Arimbawa, I., Semara Jaya, K., Semarawima, G. 2016. Cost
Minimization Analysis of Hypnotic Drug: Target Controlled Inhalation Anesthesia (TCIA) Sevoflurane
and Target Controlled Infusion (TCI) Propofol. Bali Medical Journal 5(3): 51-56.
DOI:10.15562/bmj.v5i3.300

Corresponding author: INTRODUCTION

I Gusti Ngurah Mahaalit Aribawa, MD, In the healthcare reformation era, it is
Address: Anesthesiology and Intensive Care important to be able to demonstrate some
Department, Udayana University, Sanglah economical values of a new technology. Healthcare
General Hospital, Denpasar, Bali reformation also put more pressure for
Email: mahaalit@unud.ac.id

Open access: www.balimedicaljournal.org and www.ojs.unud.ac.id 51

anesthesiologist to determine the cost impact of bleeding during the surgery >30% Estimated Blood
anesthesia strategies, drugs and technologies.1-7 Volume, (3) duration of surgery <1 hour, (4) allergic
High cost of anesthesia has always been a to propofol, (5) allergic to sevoflurane, (6) patients
problem in the hospital management. As with hypovolemic shock, (7) has a psychiatric
pharmacology and technology advance, there are disorder, (8) presents neurological deficits (9) has a
various anesthesia techniques and the development heart and blood vessels disease and have
of anesthesia depth monitoring tools which could experienced a cerebrovascular event.
assist anesthesiologist in determining the drug using The sample was taken using a consecutive
and appropriate dosages. The development of sampling technique. They were divided into two
computerized systems and availability of short groups by randomized blocks: 30 people in one
acting drugs such as propofol and sufentanyl, made group received a general anesthesia TCIA
the target controlled infusion (TCI) increasingly sevoflurane, and 30 others in another group received
used for total intravenous anesthesia.8 Anesthesia a general anesthesia TCI propofol. The participants
inhalation technique has been making progress as flow details are available in Chart 1 and Chart 2. An
well, with a low fresh gas flow 2 liter per minute analysis of cost comparison was also conducted
(lpm) and target controlled inhalational anesthesia between TCIA sevoflurane and TCI propofol. The
(TCIA) with end tidal (ET) control which is a data analysis used the Statistical Package for Social
conductive anesthesia system available in newer Sciences for Windows (SPSS Inc., Chicago, version
anesthesia machine. It is a kind of anesthetic gas 20.0).
conductor system, in which the machine would
automatically adjusts the concentration of anesthetic RESULTS
agents to achieve the desired target level set by the The age in both groups are normally
user.9-11 distributed. The age in the TCIA sevoflurane group
We were determined to do a research on cost ranged from 22-63 years, with an average of 47.7
minimization analysis of hypnotic drug used for years (SD 9.9). The age in the TCI propofol group
general anesthesia with manually controlled TCIA ranged from 31-63 years, with an average of 51.6
sevoflurane and TCI propofol in Sanglah General years (SD 7.8). Based on the gender, the TCIA
Hospital 2016. sevoflurane group consists of 8 men and 22 women
(26.7% and 73.3% respectively). The TCI propofol
METHODS group consists of 5 men and 25 women (16.7% and
This study is an experimental design with non- 78.3% respectively). Based on the ASA physical
blind randomized controlled trial. The clinical trials status, the TCIA sevoflurane group consists of 11
were conducted on 60 patients who met the ASA I (36.7%) and 19 ASA II (63.3%), while the
eligibility criteria who underwent mastectomy TCI propofol group consists of 8 ASA I (26.7%) and
surgery and thyroidectomy in Sanglah General 22 ASA II (73.3%). Based on the Body Mass Index
Hospital from January to March 2016. (BMI), the TCIA sevoflurane group ranged from
The inclusion criteria are: (1) admitted in our 19.1 to 24.8 kg/m2, with an average of 22.2 kg/m2
hospital from January to March 2016, (2) ASA (SD 1.8). The BMI in the TCI propofol group ranged
physical status I-II, (3) 16-64 years old by the time from 17.9 to 24.5 kg/m2, with an average of 21.7
of the admission, (4) the body height is more or kg/m2 (SD 1.9). Based on the type of the surgery,
equal to 130 cm, (5) the body mass index is 18.5 the TCIA sevoflurane group consists of 17 people
kg/m2 - 24.5 kg/m2, (6) willing to undergo surgery underwent mastectomy (56.7%) and 13 people
with general anesthesia technique TCIA sevoflurane underwent thyroidectomy (43.3%). While in the TCI
or total intravenous use of TCI propofol by signing propofol group, 18 people underwent a mastectomy
the informed consent, (7) the patient uses one of the (60%) and 12 thyroidectomies (40%).
following insurance as a mean of payment: National An adverse event recorded in both groups was
Health Insurance (JKN), Bali Mandara Health post-induction hypotension. The incidence of other
Insurance, Health Insurance for the Poor side effects such as agitation, nausea, vomiting,
(JAMKESMAS), Indonesian National Social bronchospasm, cough, bradycardia and tachycardia
Security System (BPJS). did not occur. In the TCIA group the incidence of
The exclusion criteria are: (1) the patient hypotension occurred was 20.0% (n=6), whereas in
refused to participate as a research subject, (2) the the TCI propofol group was 16.75% (n=5). Table 2

Open access: www.balimedicaljournal.org and www.ojs.unud.ac.id 52

shows there is no significant difference between the General Hospital pharmacy in December 2015 was
two groups (p=0.739), based on the Pearson chi- IDR (Indonesian Rupiah) 1,465,000 per 250 ml
square test. bottle, while the propofol price was IDR20,782 per
200 mg ampoule. This means, the sevoflurane price
Table 1 Comparison of The Duration of Surgery, was IDR5,860/ml and the propofol IDR103.91/mg.
The Duration of Anesthesia and The Total Drug
Used
Group
TCIA TCI
Sevoflurane Propofol
n=30 n=30
Duration of surgery
202.00 (73) 195.50 (61)
(minutes, IQR)
Duration of
anesthesia 233.50 (81) 230.00 (71)
(minutes, IQR)
Total Drug Used
Sevoflurane Figure 1
29.06 ± 8.30
(ml ± SD) Comparison of Recovery Time between The Two
Propofol 1723.50 ± Groups (axis: time of recovery in minutes)
(mg ± SD) 474.93
Propofol as an intravenous drug could not
Ratio of drug used per unit of time
simply be calculated per ml usage, but it is counted
Sevoflurane by the number of the opened ampoules. However,
0.12 ± 0.03
(ml/minute ± SD) the cost minimization analysis between the two
Propofol groups has no significant difference. The price of the
7.25 ± 0.98
(mg/minute ± SD) hypnotic drug cost for induction and maintenance in
TCIA sevoflurane group was IDR152,360 (IQR
Table 2 Comparison of Hypotensive Incidents Post- 70,320), while in the TCI propofol the price was
induction Between The Two Groups IDR187,038 (IQR 41,564). Based on the Mann-
Group Whitney U test, the cost minimization analysis from
Side Effects TCIA TCI p the two groups has no significant difference
Sevoflurane Propofol (p=0.146). Table 3 shows the hypnotic drug cost per
n=30 n=30 minute was IDR598.43 (IQR 112.47) in the TCIA
f(%) f(%) sevoflurane group, while the TCI propofol group
Hypotensive 6 (20%) 5 (16.7%) 0.739 was IDR703.27 (IQR 156.73). However, the
Incident statistical analysis shows no significant difference
between the two groups (p=0,138). In emodynamic
parameters, based on the mean arterial pressure
Figure 1 shows the median recovery time in
which was depicted on TAR1 (baseline mean
the TCIA sevoflurane group was 8 minutes, faster
arterial pressure), the obtained mean difference is
than the median recovery time in the TCI propofol.
2.7 (1.4-6.8, 95%CI). The mean difference of the
It also shows a wider distribution of recovery time
post induction mean arterial pressure (TAR2) is 2.6
in the TCIA sevoflurane group than the TCI
(-3.0-8.2, 95%CI). The mean difference of the post
propofol group. It can be concluded that there was a
intubation mean arterial pressure is 2.9 (-6.0-5.2,
statistically significant difference in recovery time
95%CI). The result indicates that in the population,
between the two groups (p<0.05).
the TAR clinical value did not differ between those
The total average use of TCIA sevoflurane per
two groups at a 95% confidence interval. The heart
anesthetic duration was as much as 0.12 ml/min (7.2
rate variable consists of N1 as the baseline heart rate,
ml/hour). While the TCI propofol average use per
and N2 as the post induction heart rate, and N3 as
anesthetic duration was 7.25 mg/min (435.0
the post intubation heart rate. The mean difference
mg/hour). The sevoflurane unit price in Sanglah
of the N1 is 2.3 (-3.1-7.7, 95%CI).

Open access: www.balimedicaljournal.org and www.ojs.unud.ac.id 53

 Bali Medical Journal (Bali Med J) 2016, Volume 5, Number 3: 51-56
P-ISSN.2089-1180, E-ISSN.2302-2914

Inhalational Anesthesia (TCIA)

TCI Group
Group

Prepare and record all anesthetic drugs, evaluate hemodynamic status

Prepare and record all anesthetic drugs, evaluate hemodynamic status (T1); (T1); systolic and diastolic blood pressure, heart rate, and mean arterial
systolic and diastolic blood pressure, heart rate, and mean arterial pressure pressure before the patient got anesthetized
before the patient got anesthetized

Co-induction Fentanyl 2 µg /kgbw, Ketorolac 0,5-0,75 mg/kgbw (5 min pre-induction),

Co-induction Fentanyl 2 µg /kgbw, Ketorolac 0,5-0,75 mg/kgbw (5 min pre- Induction with TCI Propofol Schnider mode with target effect concentration 4 mcg/ml
induction), Induction with Sevoflurane 8%, and oxygen 6-8 Lpm
record all anesthetic drugs,
BIS 40-60 evaluate hemodynamic status
mcgµg/ml
BIS 40-60 record all anesthetic drugs, (T2); systolic and diastolic
evaluate hemodynamic status blood pressure, heart rate, and
(T2); systolic and diastolic blood mean arterial pressure after
pressure, heart rate, and mean Intubating facility the patient got induced
Intubating facility arterial pressure after the Atracurium 0,5 mg/ kgbw
Atracurium 0,5 mg/ kgbw patient got induced

Laryngoscopy
evaluate hemodynamic status evaluate hemodynamic status
and Intubation
Laryngoscopy (T3); systolic and diastolic blood (T3); systolic and diastolic blood
and Intubation pressure, heart rate, and mean  Maintenance dose pressure, heart rate, and mean
 Maintenance dose sevofluran arterial pressure 1 min after
arterial pressure 1 min after Propofol 3 mcg/ml
end tidal 1-1,5%, Compressed Incision and
laryngoscopy and intubation  Fentanyl 0,5mcg/kgbw bolus laryngoscopy and intubation
Air 0,5 Lpm and oxygen 0,5 Incision and Surgery
every 30 minutes
Lpm Surgery  Compressed Air 2 L/menit
 Fentanyl 0,5 µg/kgbw bolus
every 30 minutes
dan O2 2 L/menit
 Atracurium intermittent  Atracurium intermittent
dose dose
BIS 40-60,
ET CO2 35-40
Maintenance ET sevoflurane 1- 1,5%, Titrate dose to 0,5 mcg/ml
BIS 40-60, ET CO2 35-40
Maintenance propofol concentration TCI
1-3 mcg/ml
Stop Sevoflurane Propofol Stop
Recovery time Recovery time (W)
(W)
Eye opening on command Eye opening on command

Recovery Room (RR) Recovery Room

(RR)
Statistical Analysis Statistical Analysis

Chart 1 Chart 2
The TCIA Participants Flow The TCI Participants Flow

Table 3 Comparison of The TCIA Sevoflurane and The TCI Propofol Costs
Group
TCIA Sevoflurane TCI Propofol
n=30 n=30 P
in IDR (IQR) in IDR (IQR)
Cost 152,360 (70,320) 187,038 (41,564) 0.146
Cost per minute of hypnotic drug 598,43 (112.47) 703,27 (156.73) 0.138

The mean difference of the N2 is -1.1 (-6-3.9, DISCUSSION

95%CI). The mean difference of the N3is -1.9 (-7.4 The total amount of sevoflurane and propofol
-3.6, 95%CI). They indicate that in the population, per duration of surgery was found different in both
the heart rate clinical value did not differ between groups, due to the different main drug in anesthetic
the two treatment groups at 95% confidence management. A previous research by Iswahyudi, et
interval. al. found that in a group treated with sevoflurane, the
In the other hand, the mean difference of the surgery lasted for 161.33 minutes (± 28.99), and the
recovery time is 3.5 (1.9-5.1, 95%CI). This result ratio of sevoflurane per time unit was 0.49 ml/min
suggests that in the population, the TCIA (± 0.077).12 In this study, a BIS monitor was used to
sevoflurane patient recovers faster rather than the facilitate the depth of anesthesia continuously,
TCI propofol patients at 95% confidence interval. In whereas Iswahyudi et al used the index of
the cost comparison of the hypnotic drug between consciousness (IOC).12-14 An end tidal was used in
the two groups, the mean difference is IDR17,399.9 our study, with a low flow control inhaled agent and
(IDR8,457-IDR43,257, 95%CI). The result technique in applied anesthesia machine. It would
indicates that TCIA sevoflurane is cheaper than the vary the amount of the volatile anesthetic agents
TCI propofol. given and inspired, depends on the fresh gas flow.
Our study shows the ratio of drug needed is 75.51%
per unit time. However, literatures stated that a

Open access: www.balimedicaljournal.org and www.ojs.unud.ac.id liv

bispectral index monitor (BIS index) could reduce (p=0.739). The incidence of hypotension is
the dose of anesthetic drug usage by up to 30%.13-14 influenced by the patient's general condition and the
In this study, the recovery time in the TCIA effect of the anesthetics during the induction phase.
sevoflurane group was 8 minutes (IQR 3), whereas The general state of the patient is a state of
in the TCI propofol group was 11.5 minutes (IQR hypovolemia before induction and the presence of
3). Despite the difference in the median recovery other comorbidities.8 In this study, the factors
time, this distinction might not have a clinical effect beyond anesthesia techniques that influence the
in ASA physical status I and II patients. But, in incidence of hypotension have been eliminated by
patients with a higher physical status ASA, it would patient exclusion. Therefore, the anesthetic
shorten the recovery time, shorten the evaluation of technique is the only factor affecting the incidence
patients, and reduce the morbidity and the cost of of hypotension.
care reduction.1-7
The cost minimization analysis between two CONCLUSION
groups shows no significant difference. The There was no significant statistical difference
hypnotic drug cost in the TCIA sevoflurane group between the cost of the target controlled inhalational
was IDR152,360 (IQR 70,320) and in the TCI anesthesia using sevoflurane with a low fresh gas
propofol was IDR187,038 (IQR 41,564). The Mann- flow 2 liter per minute compared to the target
Whitney U test shows no significant difference controlled infusion using propofol in physical status
between the two anesthetic cost (p=0.146). The cost ASA I-II patients who underwent a major oncologic
per minute of the hypnotic drug in the TCIA surgery in Sanglah General Hospital, Denpasar,
sevoflurane group was IDR598.43 (IQR 112.47), Bali, Indonesia. In contrast, based on the clinical
whereas in the TCI propofol group was IDR703.27 values, the TCIA sevoflurane group recovers faster
(IQR 156.73). The Mann-Whitney U test also shows than the TCI propofol group at 95% CI. In addition,
no significant difference (p=0.138). the cost comparison of the hypnotic drug at 95%CI
Furthermore, at 95%CI, the clinical values of shows that the TCIA sevoflurane is cheaper than the
other variables such as TAR (mean arterial pressure) TCI propofol for a major oncologic surgery with a
and N (heart rate) show no difference. But, the TCIA long duration.
sevoflurane group recovers faster than the TCI
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