Comparison of Propofol-Dexmedetomidine-Based Intravenous and Sevoflurane-Based Inhalational Anesthesia in Patients Undergoing Modified Radical Mastectomy.

BACKGROUND AND AIM: Total intravenous anesthesia (TIVA) has proven advantage over inhalational anesthesia in terms of stable hemodynamic, eco-friendly, and good recovery profile, but apprehension regarding adequate depth of anesthesia and intraoperative recall is still pertaining. This study aims to compare propofol-dexmedetomidine-based TIVA with sevoflurane-based inhalational anesthesia in modified radical mastectomy in terms of depth of anesthesia, intraoperative recall, recovery profile, and hemodynamic status. SETTINGS AND
DESIGN: This prospective randomized controlled study was conducted at a tertiary care center over a time frame of 1 year.
METHODOLOGY: In this randomized controlled study, 100 patients were randomly distributed into two groups: TIVA (Group T) and inhalational anesthesia (Group I). Group T patients received injection dexmedetomidine: 1 μg.kg-1 over 10 min followed by 0.7 μg.kg-1.h-1 and injection propofol: 25-100 μg.kg-1.min-1. Ventilation was maintained with oxygen-air gas flow. In Group I, patients were ventilated with nitrous oxide-oxygen (50:50) and sevoflurane. Rest of anesthesia for both the groups was same. Primary objective was to achieve adequate depth of anesthesia as monitored by intraoperative bispectral index value (BIS, 40-60). Hemodynamic variables, recovery profile, and amount of individual anesthetic agent consumed were recorded for comparison between two groups. For comparison of scale variables between two groups, independent sample t-test for significant difference between two sample means has been followed.
RESULTS: Intraoperative BIS and hemodynamic variables were comparable (P > 0.05). Emergence time was 5.10 min in the TIVA group versus 8.38 min in the inhalational group (P = 0.00). Modified Aldrete score was comparable in two groups (P > 0.05). Cost of TIVA agents consumed per patient was 40% lesser than inhalational agents.
CONCLUSION: TIVA maintains adequate depth of anesthesia along with stable hemodynamic and good recovery profile, at low cost in an eco-friendly manner. Copyright:

INTRODUCTION

Inhalational anesthesia is the most common mode of anesthetizing patients worldwide, but anesthetic gases are identified as potent greenhouse gases[1] which when excreted unmetabolized, contaminate air, and potentiate greenhouse effect. The average composition of the waste gases is estimated to be:[2] oxygen 25%–30%, nitrogen 60%–65%, nitrous oxide 5%–10%, and volatile halogenated anesthetic gases 0.1%–0.5%. Scavenging, low-flow, and minimal-flow anesthesia and blue–zone technologies[2] are the latest modalities to decrease the amount of gas excreted into the environment, but total intravenous anesthesia (TIVA) is the only known modality to completely avoid the use of anesthetic gases and thus air contamination. TIVA is a technique of general anesthesia which uses a combination of agents given exclusively by intravenous route. In recent years, TIVA has become more popular, practical, and possible due to the pharmacokinetic and pharmacodynamic properties of drugs such as propofol and short-acting opioids such as remifentanil along with the introduction of target-controlled infusion (TCI[3]) pumps. Further, as compared to conventional inhalational anesthesia, TIVA offers good postoperative recovery and stable hemodynamic, reduced incidence of postoperative nausea-vomiting, and lower recurrence rate in breast cancer.[4]

Despite the availability of detailed literature and known advantages, there is still apprehension regarding the adequacy of depth of anesthesia and intraoperative recall with TIVA. Wong et al.[5] did a survey to highlight the factors influencing use of TIVA such as unavailability of TCI pumps (cost may be the reason), additional expenses increasing the cost, difficult to predict wake-up, and increased incidence of awareness. Considering these issues, the present study was designed to compare TIVA with conventional inhalational mode in patients undergoing modified radical mastectomy (MRM) in terms of maintaining adequate depth of anesthesia as quantified by bispectral index (BIS), recovery profile, and cost analysis. Injection propofol and dexmedetomidine were used for TIVA via classic syringe infusion pumps against nitrous oxide and sevoflurane for inhalational mode of anesthesia in this study.

METHODOLOGY

The study was approved by the institutional ethical committee on November 19, 2018, and registered with ClinicalTrials.gov (NCT03807297). It was conducted at a tertiary care cancer center, New Delhi, from January 2019 to November 2019. Sample size was calculated using nonparametric binomial reliability demonstration test method.[6] A total of 46 patients were required in the experimental arm with one allowable failure to demonstrate minimum 90% reliability for TIVA at 95% confidence level. Assuming 20% dropout rate and rounding off to nearest tenth, 110 patients divided equally in both treatment arms were planned to be enrolled. After preanesthetic examination and written informed consent, American Society of Anesthesiologists (ASA) Grade I–III patients of age 18–65 years with body mass index (BMI) <30 undergoing MRM were included in the study [Figure 1] as per the consort flowchart and randomly divided into two groups - Group T (TIVA group) and Group I (inhalational anesthesia group) using chit in box method. Any patients with chronic kidney disease, chronic liver disease, cardiac dysfunction, and psychotic neurotic disorders were excluded from the study.

Figure 1

CONSORT flow diagram

After giving antiaspiration prophylaxis 2 h before surgery, standard ASA and BIS monitoring were applied to all patients in the operation theater. All the patients were premedicated with injection midazolam 1 mg intravenous followed by induction with injection propofol (1–2.5 mg.kg−1) and injection atracurium (0.08 mg.kg−1) for muscle relaxation. Then, as per the group allocated to the patients, anesthetic drugs were started. Group T: Injection dexmedetomidine: 1 μg.kg−1 over 10 min followed by 0.7 μg.kg−1.h−1 and injection propofol: 25–100 μg.kg−1.min−1 (dose titrated to achieve BIS between 40 and 60). Ventilation was maintained with oxygen–air gas flow. In Group I, ventilation was maintained with nitrous oxide–oxygen (50:50) along with sevoflurane (concentration adjusted to maintain BIS between 40 and 60). Once adequate muscle relaxation achieved as guided by a neuromuscular monitor, patients were intubated with an appropriate-sized endotracheal tube. Analgesia was maintained with injection fentanyl 2 μg.kg−1 and injection paracetamol 1 g intravenously. Injection morphine 1.5 mg was given as rescue analgesia (intraoperatively when there is rise in systolic blood pressure of more than 10% of baseline value along with BIS <60). All patients were ventilated with fresh gas flow at 1 L.min−1 using closed circuit in both the groups. Anesthetic agents were stopped at the last suture of skin closure in both the groups. Extubation was done once BIS value reaches >90 along with spontaneous respiration after reversing with injection neostigmine 2.5 mg and injection glycopyrrolate 0.4 mg at a train of four ratio of 0.5%.

Intraoperatively, mean blood pressure, heart rate (HR), and BIS values were recorded at different time intervals: T1 - preinduction/baseline; T2 - postintubation; T3 - postincision; T4–T9 - at regular 30 min interval post incision (30 min post-T3 value); T10 - last skin suture; T11 - postreversal; T12 - emergence time (time for BIS to attain value of 80); and T13 - postextubation.

Duration of surgery (time interval from skin incision to completion of surgery), emergence time (time to reach BIS value of 80 after stoppage of anesthetic agents in respective groups), and extubation time (end of surgery to removal of endotracheal tube) were noted.

Patient's satisfaction about the quality of anesthesia (intraoperative awareness using Brice interview) and modified Aldrete score (MAS, which consists of 8 points i.e., activity, respiration, circulation, consciousness, oxygen saturation, pain, surgical bleeding, and nausea-vomiting) were recorded postextubation. At the end of each case, the amount of each anesthetic agent consumed was also recorded, i.e., nitrous oxide, sevoflurane, propofol, and dexmedetomidine, for cost analysis. Primary outcome of the study was to achieve adequate depth of anesthesia (measured as BIS value 40–60). Secondary outcomes of the study were recovery profile, hemodynamic parameters, and cost of anesthetic agents consumed in individual groups. Carbon dioxide equivalents (CO2e) produced by inhalational agents were also calculated for academic interest.

For comparison of scale variables between TIVA and inhalational groups, independent sample “t” test for significance difference between two sample means has been followed. Mean and standard deviation have been computed using descriptive statistic procedure. For two-sided test of significance, the cutoff P < 0.05 has been taken. Data analysis has been done using IBM SPSS Statistics 24, SPSS software, South Asia Pvt. Ltd.

RESULTS

There was even distribution of age (P = 0.190), weight (P = 0.225), height (P = 0.175), and BMI (P = 0.460) in both the groups (P > 0.05) as shown in Table 1. All patients in Group T and I were able to achieve BIS value between 40 and 60 proving that adequate depth of anesthesia was achieved. It was comparable in both the groups at all the time points (P > 0.05) [Figure 2].

Table 1

Demographic and recovery (emergence time and extubation time) profile along with total duration of surgery for both the groups

Parameter	Mean±SD		P
	TIVA (n=50)	Inhalational (n=50)
Age (years)	51.38±7.89	49.24±8.31	0.190
Weight (kg)	63.02±9.02	65.14±8.35	0.225
Height (m)	1.56±0.06	1.57±0.05	0.175
BMI (kg/m2)	25.83±2.82	26.25±2.84	0.460
Total duration of surgery (min)	135.88±41.67	140.62±41.00	0.568
Emergence time (min)	5.10±1.5	8.38±3.8	0.000
Extubation time (min)	5.12±1.4	7.92±3.6	0.000
Morphine (mg)	3.69±0.76	4.14±0.71	0.003
MAS	15.08±3.35	15.24±0.96	0.746

MAS has no unit with maximum score of 16. Values are mean±SD with P values. SD=Standard deviation, TIVA=Total intravenous anesthesia, BMI=Body mass index, MAS=Modified Aldrete score

Figure 2

Bispectral index values at different time intervals between two groups

Rise in HR was significantly lower in Group T patients as compared to Group I at postintubation (T2) (P = 0.003) and postextubation (T13) (P = 0.000), whereas it was comparable at all other time points [Figure 3]. Similarly, the rise in mean arterial pressure at T2 (postintubation), P = 0.003 and T13 (postextubation), P = 0.000 was significantly lower [Figure 4], as compared to other time points.

Figure 3

Heart rate (beats/min) at different time intervals between two groups

Figure 4

Mean arterial pressure (mm of Hg) at different time intervals between two groups

Group T had a lesser requirement of morphine, shorter emergence time, and shorter extubation time compared to Group I with a statistically significant P value, whereas MAS was comparable in both the groups as shown in Table 1. None of the patients reported any recall of events (as analyzed by Brice interview) and were satisfied with the quality of anesthesia. The average duration of surgery was comparable [P = 0.568, Table 1] in two groups: 135 and 140 min in Group T and I, respectively.

One cylinder of nitrous oxide consisting of almost 15.7 l of gas which costs to hospital at Rs. 194 (rupees 12.33/l), sevoflurane charged to patient at Rs. 35/ml, one vial (100 mg) of propofol at Rs. 170, and one ampoule (200 μg) of dexmedetomidine at Rs. 230. Using these costs and the average amount of individual anesthetic agents consumed per patients, the mean cost of anesthesia per patient for TIVA was Rs. 781.00 ± 126, which was found to be nearly half (48.4%) of the mean cost of the inhalational group, i.e., Rs. 1613.00 ± 413.00 (P = 0.000) [Table 2]. The median cost of anesthesia in the TIVA group was Rs. 740.00 with interquartile range (IQR) of 740–910, while the median cost and IQR in the inhalational group were Rs. 1524.00 and Rs. 1295.00–1868, respectively.

Table 2

Average cost per patient in two groups

Statistics	Group
	TIVA	Inhalational
Number of observations	50	50
Mean±SD (Rs.)	781±126	1613±419
Minimum (Rs.)	570	1020
Maximum (Rs.)	1080	2682
Percentiles (Rs.)
Q1 (1st quartile)	740	1295
Q2 (median)	740	1524
Q3 (3rd quartile)	910	1868

Values in mean±SD, minimum and maximum, percentiles in INR. P value of independent sample t-test=0.000. SD=Standard deviation, TIVA=Total intravenous anesthesia, INR=International normalized ratio

Two-hundred and fifty milliliters of sevoflurane produces 49 kg[7] of CO2e with a global warming potential (GWP100) of 130. In our study, total sevoflurane consumption by 50 patients was 788 ml which thus produces 154.448 kg of CO2e. Nitrous oxide has a GWP100 of 310.[7] 4305 l of nitrous oxide was consumed by 50 patients in this study which in turns produce 2641.2 kg of CO2e [Table 3]. Thus, 2795.648 kg of CO2e was produced by the consumption of inhalational agents in this study.

Table 3

Total amount of carbon dioxide equivalents produced by 50 patients operated under inhalational anesthesia (kg)

Anesthetic gases	Total consumption (Group I)=50 patients	Density of agents (kg)/1000 L	Weight (kg)=Density×volume (L)	GWP100	CO2e (kg)=Weight (kg) × GWP
Nitrous oxide	4305 L	1.97	8.52 kg	310	2641.2
Sevoflurane	788 ml			130	154.448
Total					2795.648

GWP=Global warming potential, CO2e=Carbon dioxide equivalents

DISCUSSION

Dexmedetomidine, an α-2a agonist, is a novel sedative with analgesic properties that controls stress, anxiety, and pain. The hypnotic and sedative effects of α2-adrenoceptor activation have been attributed to locus coeruleus in the central nervous system which is an important modulator of vigilance. This property of dexmedetomidine in cumulation with sedative properties of propofol resulted in successfully achieving adequate depth of anesthesia during surgery as proved by intraoperative BIS value between 40 and 60 in this study. BIS is a continuous noninvasive electroencephalographic method that has been proposed to monitor the hypnotic state during sedation and anesthesia.[89] BIS-monitored anesthesia is an indicator of decrease risk of intraoperative awareness under general anesthesia.[10]

As Mishra et al.[11] commented, both the groups in our study had comparable hemodynamic during intraoperative period. However, P value was 0.000 postextubation, which indicates better hemodynamic stability in the TIVA group. This was a positive result toward the use of TIVA and could be attributed to dexmedetomidine which causes activation of the postsynaptic alpha-2 adrenoceptors, inhibiting the sympathetic activity, leading to decreased blood pressure and HR. Further, all the patients in the TIVA group had comparable MAS, i.e., 15.08/15.24, which is a very good postoperative recovery score. Mishra et al. also revealed that TIVA group patients had clear headed awakening and better orientation to place than the inhalational group. Buchh et al.[12] had also produced similar results in their study on day-care gynecological surgeries, where TIVA group patients had Aldrete score ≥9. Contrary to the belief, the emergence time, extubation time, and recovery time were more rapid in the TIVA group compared to inhalational group, with a statistically significant P = 0.000. Moreover, attenuation of the neuroendocrine and hemodynamic responses to anesthesia and surgery by dexmedetomidine reduces anesthetic and opioid requirements and causes sedation and analgesia. This can explain the statistically significant lower consumption of morphine in the TIVA group (P = 0.003) of patients. This decreased morphine consumption due to the use of dexmedetomidine can be an integral part of opioid-free anesthesia and thus can be incorporated into ERAS protocol.

Every year, globally, approximately 200 million anesthetic procedures release inhaled anesthetics into the atmosphere causing a climate impact that is equivalent to 0.01% of that of the carbon dioxide (CO2) released from global fossil fuel combustion.[113] An equivalent of 6% of global CO2 emissions results from nitrous oxide, and 1% of these is medicinal[14] per year. Together desflurane, sevoflurane, and isoflurane contribute around 0.08 MtCO2 to the carbon footprint.[15] CO2e[7] is a quantity that describes, for a given mixture and amount of greenhouse gas, the amount of CO2 that would have the same GWP when measured over a specified timescale (generally, 100 years). This study has also stated that the use of inhalational agents causes addition of CO2e to the environment (2463 kg in this study) as opposed to TIVA where CO2e is zero.

Most of the anesthetists use TCI pumps for TIVA. As these are costlier pumps and not available at all the centers, especially in low-cost healthcare facility, we have successfully used classic syringe infusion pumps for intravenous infusions in our study. The standard infusion doses of both the drugs were used to maintain a BIS of 40–60 (25–100 μg.kg−1.min−1 for propofol and 0.7 μg.kg−1.h−1 for dexmedetomidine). Moreover, studies suggest that, compared to syringe infusion pumps, consumption of propofol is more with TCI pump with the same recovery profile,[16] thus increasing the total dose of anesthetic agents consumed and thus cost. This study has also analyzed the cost-effectiveness in terms of anesthetic agents. The cost of anesthetic agents consumed per patient in TIVA was 40% of cost per patient in the inhalational group. This is a significant result as it implies that TIVA, apart being eco-friendly, is also cheaper for the patient. Some anesthesiologists may argue that using low-flow absorption breathing systems can also be economic and they are also been recommended to reduce atmospheric pollution.[1718] However, the economies and reduced emission inherent in the circle breathing system cannot be exploited for short surgical procedures because of the initial high fresh gas flows required to achieve denitrogenation and uptake of anesthetic agents.[1719]

Limitations of the study

We have considered only the amount of anesthetic drugs consumed for cost analysis. As, due to routine surgical protocol, all patients were kept in postanesthesia care unit for at least 6 h and were discharged after minimum of 48 h, we were not able to analyze the total cost-effectiveness as most of other costs remained same.

CONCLUSION

Propofol–dexmedetomidine-based TIVA using standard infusion pumps is a cheaper and eco-friendly mode which provides adequate depth of anesthesia without any intraoperative recall.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.