Comparative evaluation of cost effectiveness and recovery profile between propofol and sevoflurane in laparoscopic cholecystectomy.

BACKGROUND: Anesthetic agents should be chosen not only on the basis of safety-efficacy profile, but also on the economic aspect. Propofol and sevoflurane are commonly utilized anesthetic agent for general anesthesia. AIM: The present study was designated to compare cost-effectiveness and recovery profile between propofol and sevoflurane for induction, maintenance or both. SETTINGS AND
DESIGN: Randomized controlled, participant and data operator blinded trial.
MATERIALS AND METHODS: Ninety patients undergoing laparoscopic cholecystectomy were randomized into three equal groups to receive: Group P to receive injection propofol for both induction and maintenance; Group PS to receive injection propofol for induction and sevoflurane for maintenance; and Group S to receive sevoflurane for both induction and maintenance of general anesthesia, respectively. Cost analysis, hemodynamic parameter, and recovery profile were compared between these groups. STATISTICAL ANALYSIS: One-way analysis of variance test or Fisher's exact test/Chi-square test whichever appropriate.
RESULTS: Total cost of anesthesia was highest in Group P and lowest in Group S. Mean time to extubation and time to follow verbal commands was lowest in Group S than Group P or Group P/S. Hemodynamic parameter was more stable in Group S.
CONCLUSION: We conclude that sevoflurane appears to be better anesthetic agents in terms of cost-effectiveness and recovery profile.

RCT Entities:   Population Interventions Outcomes

INTRODUCTION

Clinical efficacy, pharmacokinetic profile, and economic feasibility plays a critical role while selecting an anesthetic agent for a particular surgical procedure.[12] In routine practice, anesthesiologist prefers an anesthetic agent with which they are familiar with or tailor an anesthetic technique considering its safety-efficacy profile, without giving much consideration to the associated economic burden with the armamentarium. Various factors which may effectively decrease the anesthetic cost include favorable operative conditions, use of the standardized protocol, aseptic conditions, and prohibition of money-making culture in the interest of patient care.

Review of previous literature on the economic feasibility of a drug reveals a comparison between total intravenous (IV) anesthesia and inhalational anesthesia prominently by direct cost measurements, which may lead to a faulty interpretation.[34] Utilized methodology includes calculation of drug costs on the basis of average infusion dose/flow rates, without considering the issues like drug wastage and the effects of changing fresh gas flow rates or vapor settings of inhalational agent, cost of consumables, and the duration of anesthesia.[56] Overall cost-effectiveness should also balance the cost of an anesthetic agent with its pharmacodynamics effects such as efficacy, dose requirement, and recovery profile. Thus, the present study was designated to compare cost-effectiveness and recovery profile between propofol and sevoflurane for patients undergoing laparoscopic cholecystectomy.

MATERIALS AND METHODS

After Institutional Ethical approval and written informed consent, 90 patients aged 18–65 years, of either sex, of American Society of Anesthesiologists (ASA) grade I or II scheduled for laparoscopic cholecystectomy in between February and December 2014 were included in this randomized controlled, participant and data operator blinded trial. Patients with a history of end-organ dysfunction, allergy to anesthetic drugs, morbid obesity, or pregnancy were excluded.

All patients were randomized (computer generated randomization and concealment via sealed opaque envelope technique) into three equal groups: Group P to receive injection propofol for both induction (dose: 1–2.5 mg/kg, IV) and maintenance (dose: 50–150 μg/kg/min, IV) of general anesthesia (GA); Group PS to receive injection propofol (dose: 1–2.5 mg/kg, IV) for induction and sevoflurane (1–3%) for maintenance of GA; and Group S to receive sevoflurane for both induction (8%) and maintenance (1–3%) of GA. Randomization was performed by an investigation involved in drug administration and data collection. Data analysis was carried out another investigator blinded to group allocation.

Premedication included tablet alprazolam (0.50 mg), tablet ranitidine (150 mg), and tablet metoclopramide (10 mg) administered orally on the evening before surgery and 2 h before the scheduled procedure. On arrival to the operative room, monitors were placed and baseline parameters recorded. Each patient received injection fentanyl (2 μg/kg, IV) during induction and repeated at every 30 min (dose: 1 μg/kg, IV) during intraoperative period. As per group allocation, anesthesia was induced with either injection propofol IV until disappearance of verbal response or sevoflurane until loss of consciousness and endotracheal intubation was facilitated with injection vecuronium (0.1 mg/kg, IV). GA was maintained with nitrous oxide: oxygen combination (1:1) and continuous infusion of injection propofol or sevoflurane inhalation as per group allocation, to maintain the bispectral index level in between 50 and 60 during intraoperative period. Fresh gas flow was maintained at 2 l/min throughout this period. Neuromuscular blockade was maintained by injection vecuronium (0.02 mg/kg, IV) as required throughout surgery. At the end of surgery, muscle relaxation was reversed with injection neostigmine (0.05 mg/kg, IV) and injection glycopyrrolate (0.01 mg/kg, IV). Patients were extubated and transferred to postoperative unit.

All patients were observed for the cost of studied drugs, duration of anesthesia, and time from termination of anesthetic agent to return of response to verbal commands, hemodynamic stability (mean blood pressure [MBP], heart rate [HR]), mean extubation time, and any associated intraoperative side effects. Primary outcome included the cost analysis defined as the costs of studied drugs (including both consumed and wasted) for induction and maintenance of anesthesia, and the disposable items required for its administration (Appendix). Other intraoperative drugs and consumables common among the compared groups were excluded from cost comparison. The cost for the period of the different sevoflurane settings were calculated according to the formula (cost (Indian national rupees [INR]) = P*F*T*M*C/2.412*d), where P was vaporizer setting (%), F was fresh gas flow (2 l/min), T was the duration of sevoflurane administration (min), M is the molecular weight of sevoflurane (200), C is the cost (rupees per ml) of sevoflurane, and d is the density of sevoflurane (1.52 g/ml).[67] The cost of each period were added up to obtain the total costs of sevoflurane. Mean extubation time was defined as the time point from the termination of studied drug infusion/inhalation to endotracheal extubation at the end of surgery. Hemodynamic parameters will be assessed immediately after induction, at intubation and after extubation at 5, 30, and 60 min, respectively.

To detect a 20% difference in the primary outcome between the compared groups with a standard deviation of 25% (estimated from initial pilot observations), with 80% power and 5% alpha error (two-sided); a sample size of 26 per group was required. The sample size was calculated by power and sample size calculator of Department of Biostatics, Vanderbilt University, USA. To take care of any dropouts, we selected 90 patients (30 in each group) for our study.

The statistical analysis was performed with IBM SPSS Statistics for Windows, Version 16.0, (Armonk, NY: IBM Corp). The continuous variables were compared by one-way analysis of variance test. Discrete variables were compared by Fisher's exact test/Chi-square test, whichever appropriate. A P < 0.05 was considered significant.

RESULTS

All the 90 selected patients completed the study successfully [Figure 1]. The study groups were comparable in terms of demographic profile, Baseline hemodynamic variables, ASA status, IV fluid infused, estimated blood loss, intraoperative fentanyl requirement, and the duration of surgery [Table 1].

Figure 1

Flowchart of patient studied

Table 1

Comparison between demographic profile and intraoperative parameters (n=30)

Measured total anesthetic cost was maximal for Group P, while minimal in Group S (P < 0.001) [Table 2]. The anesthetic cost excluding the wasted drugs was highest in Group P, while lowest in Group PS. Similarly, the maintenance cost of anesthesia and the costs of disposable items were highest in Group P and lowest in Group S. However, the isolated cost of induction was significantly highest in Group S and lowest in Group P [Table 2].

Table 2

Comparison of cost analysis (n=30)

There was significant fall in HR and MBP from baseline values after induction of anesthesia in all three groups, but lesser in Group S [Figures 2 and 3]. After intubation, there was a transient increase in above parameters from baseline value in all the groups [Figures 2 and 3]. Hemodynamic variables remained stable for the remaining period of observation in all the groups.

Figure 2

Intragroup comparison of mean heart rate (beats per minute) from baseline parameters at different time intervals. Data presented as mean ± standard deviation. P <0.05 considered as significant (*P < 0.01, **P < 0.001)

Figure 3

Intragroup comparison of mean blood pressure (mmHg) from baseline parameters at different time intervals. Data presented as mean ± standard deviation. P <0.05 considered as significant (#P < 0.05, *P < 0.01, **P < 0.001)

Mean extubation time and time to follow verbal commands was significantly longer in Group P, while the above parameters were comparable between the Groups PS and S. Side effects did not vary significantly among the groups [Table 3].

Table 3

Comparison of postoperative parameters and incidence of side effects between the groups (n=30)

DISCUSSION

A quick look at the unit price of individual studied drugs gives an impression of expensive anesthetic cost by the use of sevoflurane in comparison to propofol. However taking into account, amount of drug utilized during surgery, cost of disposable items, and unutilized drug wasted after surgery, our observation indicates that sevoflurane is most cost-effective for longer duration surgeries considering the lowest cost of maintenance, favorable recovery profile, no drug wastage or need of disposable items for its administration.

Higher total anesthetic cost in propofol group could be attributed to wastage of unused drugs, greater maintenance cost and need for disposable items like pressure monitoring line and syringes for intraoperative infusion. Higher induction cost in sevoflurane group could be an effect of drug consumption in priming the anesthesia circuit and higher fresh gas flow requirement for anesthetic induction. For shorter duration surgeries, the anesthetic cost may be minimized by induction with propofol, and utilizing sevoflurane for maintenance, taking into account lowest cost of induction with propofol and minimal maintenance cost of anesthesia with sevoflurane. These findings are line with similar observations by Smith et al. comparing sevoflurane and propofol for day care surgeries.[7] In contrary, Thwaites et al. observed a lower induction cost with sevoflurane in comparison of propofol for patients undergoing day care cystoscopy.[8] These results could be attributed to the calculation of drug cost on the basis of actual consumption of IV propofol without considering the cost of disposable items.

After anesthetic induction, a significant fall in HR and MBP in the groups could be a result of sympathetic cut-down or direct cardiac depression both by propofol and sevoflurane. Ogawa et al. also observed a similar decline in HR during induction of anesthesia with both sevoflurane and propofol.[9] Shorter mean time to extubation and response to verbal commands with sevoflurane is an expected phenomenon and results from the rapid drug elimination after tapering off sevoflurane. Peduto et al. showed that sevoflurane is a better anesthetic agent in terms of recovery profile for day case surgeries.[10] Similarly, Robinson et al. found that the patients maintained on sevoflurane anesthesia responded to commands 3–4 min earlier in comparison to propofol.[11] Höcker et al. however observed a shorter extubation time with propofol infusion in comparison to maintenance with sevoflurane.[12] These observations could be attributed to differences in duration of surgical procedure and comparison on patients of different ethnic group and population. Another study by Arar et al. found no difference between sevoflurane and propofol as regards to extubation time and other emergence characteristics.[13] The selection of geriatric patients as an inclusion characteristic could have blunted any difference between the two groups in this study.

We observed no significant complications except for nausea/vomiting, shivering, and emergent agitation in few patients, with nonsignificant intergroup differences. Cohen et al. observed similar results with no difference in vomiting episodes in their study groups.[14] Caverni et al. compared sevoflurane and propofol in patients undergoing long-term craniofacial surgeries, and found no differences in postoperative complication in between the groups.[15]

Our study has two main limitations. First, the anesthetist involved in drug administration also performed the data measurements. Thus the outcome monitoring was not blinded. However, the cost measurements were performed by data operator blinded to study methodology; thus, this may add veracity to our findings. Second, these results may vary from studies performed on other ethnic groups considering the disparity in drug cost among different countries and also variations in subjective anesthetic sensitivity may contribute to differences in drug requirement.

To conclude, sevoflurane appears to a cost efficient anesthetic agent in terms of lower maintenance cost of anesthesia and better recovery profile. Additional advantages include no drug wastage or need of disposables for its administration.