|Year : 2013 | Volume
| Issue : 3 | Page : 328-332
Pharmaco-economics: Minute-based cost of sevoflurane in pediatric short procedures and its relation to demographic variables
Preet Mohinder Singh, Anjan Trikha, Renu Sinha, Rashmi Ramachandran, Vimi Rewari, Anuradha Borle
Department of Anaesthesia, All India Institute of Medical Sciences, New Delhi, India
|Date of Web Publication||27-Aug-2013|
Department of Anaesthesia, All India Institute of Medical Sciences, New Delhi
Source of Support: None, Conflict of Interest: None
Background: Inhalation agents account for significant cost of short daycare procedures. The estimation of this cost to pre-calculate expected expenditure is not available in literature. As for intravenous agents, their relations to weight and other demographic parameters are also not well established. The present study aims to evaluate the above concern.
Materials and Methods: A total of 100 pediatric (ASA I, II) patients scheduled for ophthalmological examination under anesthesia (EUA) were included in the study. Following premedication, anesthesia in all children was induced using incremental concentrations of sevoflurane at a flow of 6 l with 1:1 oxygen:nitrous oxide ratio. Upon induction, the flows were reduced to 2 l, keeping sevoflurane at 1 to 2 minimum alveolar concentration (MAC). Using Dion's equation, the costs for induction and maintenance with sevoflurane were calculated for each patient.
Results: The cost per minute of sevoflurane was found to be Rs. 13.23. Unlike intravenous agents, no significant correlation was found to exist between sevoflurane consumption with age or weight. The sevoflurane consumption was also not influenced by the gender. The total cost of EUA correlated most strongly with duration of maintenance phase, followed by induction duration.
Keywords: Examination under anesthesia, pharmaco-economics in anesthesia, sevoflurane cost
|How to cite this article:|
Singh PM, Trikha A, Sinha R, Ramachandran R, Rewari V, Borle A. Pharmaco-economics: Minute-based cost of sevoflurane in pediatric short procedures and its relation to demographic variables. J Anaesthesiol Clin Pharmacol 2013;29:328-32
|How to cite this URL:|
Singh PM, Trikha A, Sinha R, Ramachandran R, Rewari V, Borle A. Pharmaco-economics: Minute-based cost of sevoflurane in pediatric short procedures and its relation to demographic variables. J Anaesthesiol Clin Pharmacol [serial online] 2013 [cited 2019 Nov 17];29:328-32. Available from: http://www.joacp.org/text.asp?2013/29/3/328/117083
| Introduction|| |
Examination under anesthesia (EUA) in children is a common procedure performed by many centers around the world. Usually these procedures are short and non-invasive. Most of these procedures are performed on a daycare basis using sevoflurane for induction and maintenance of anesthesia. It can be easily assumed that the cost of sevoflurane used during the procedure forms a major proportion of the economic variable during these procedures, as usually these procedures do not require supplementation with other anesthetic drugs like neuromuscular blockers (NMBs) and opioids. However, the cost of inhalational agents used does not feature separately while calculating the total anesthesia-related expenditure. This could mainly be because there is scanty literature regarding the actual calculation of the amount of inhalational agent used in relation to the duration of procedure, as well as the demographic profile of the patient. There are no studies validating the effect of patient demographics, i.e., age, sex, and weight while the same is well-known with intravenous anesthetic drugs. For centers with heavy loads of pediatric patients like in ophthalmological units, EUAs form a significant proportion of procedures being performed under general anesthesia. Estimation of cost of these procedures will help not only to quantify inhalation agent's requirement but also underline any possible wastage of the agent. For centers charging the patients on per case basis, such estimates can be useful for determining anesthesia-related costs. For government centers, this can help to estimate stocks and also to manage economic resources toward amount of inhalation agents required. This usage of sevoflurane is significantly higher in EUAs than other routine procedures as it needs high flows not only while induction but also during the maintenance of anesthesia due to avoidance of low flows in pediatric population with spontaneous ventilation and, thus, the above estimates assume more importance.
| Materials and Methods|| |
The present study aimed to evaluate per minute-based cost of short procedures under general anesthesia. After obtaining institutional ethical clearance, this prospective study was carried out in an ophthalmological center of a tertiary care hospital. The study included 100, ASA I and II pediatric patient aged between 1 and 8 years. Patients with the following were excluded from the study: Known seizure disorder, craniofacial abnormalities/difficult airway, cardiopulmonary or neuromuscular defects, hepatic or renal insufficiency.
All patients were scheduled for ophthalmological examination under general anesthesia. A written/informed parental consent was obtained for participating in study and all patients were premedicated with 0.5 mg/kg of oral midazolam half an hour prior to the procedure. The induction of anesthesia was carried out using incremental concentrations of sevoflurane with a fresh gas flow of 6 l with oxygen and nitrous oxide in 1:1 ratio. The induction was started from 1% sevoflurane dial concentration and sevoflurane concentration was stepped up by 1% every 4 th breath until 8% dial concentration was achieved. The dial setting was maintained at 8% until adequate depth of anesthesia was achieved (adjudged by central position of eyeball and adequate jaw relaxation), thereafter sevoflurane concentration was reduced to 4% and an intravenous line was secured, following which optimal size classic laryngeal mask airway (LMA) was inserted. For the maintenance phase, the total fresh gas flow was reduced to 2 l (oxygen:nitrous oxide = 1:1). Adequate depth of anesthesia during maintenance phase for EUA was maintained using one to two minimum alveolar concentrations (MACs) of combined sevoflurane and nitrous oxide, following high concentration of sevoflurane during induction requiring a dial setting between 1% and 2% only. The clinical predictors used for adequate depth were central eye position, stable hemodynamics on eye handling, and the absence of response to application of eye speculum. An observer noted the time duration for each concentration during induction and maintenance in seconds. The values of time, flow, and concentration were substituted in Dion's equation and the volume of liquid sevoflurane consumed was calculated as below:
Total cost = Induction cost + Maintenance cost
Dion's equation gives total amount of liquid sevoflurane consumed as, 
Liquid sevoflurane consumption = PFTM/2412d
Where, the variables represent
P Vaporizer dial concentration in percent
F Total fresh gas flow in l/min
T Time for which the concentration P was set in minutes
M Molecular mass of sevoflurane in grams
d Density of liquid sevoflurane in g/ml
The retail price of sevoflurane available in the Indian market is Rs 5,500 per 250 ml bottle. Thus, the cost per milliliter was calculated to be Rs. 22/ml. The results of consumed volumes were multiplied to get the corresponding costs.
| Results|| |
The statistical analysis was performed using SPSS version 20 (IBM Inc.) for MAC. The mean age of patients was found to be 3.295 ± 1.820 years. The mean weight of patients was found to be 11.55 ± 3.52 kg. Thirty-six percent were females and 64% patients were males. The mean total duration from induction to LMA removal at the end of procedure was 11.91 ± 6.086 min. No statistically significant correlation of cost of sevoflurane consumed with age (Spearman's correlate = −0.049, P = 0.629) [Figure 1] and with weight (Spearman's correlate = −0.019, P = 0.854) [Figure 2] could be found. The cost had direct stronger correlation to the total duration of procedure than to the total time taken for induction of anesthesia. Induction spearman's correlation coefficient was 0.466 (P < 0.001) versus total duration Spearman's correlation coefficient of 0.554 (P < 0.001).
|Figure 1: Scatter graph showing correlation between amount of sevoflurane (ml) consumed and age|
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|Figure 2: Scatter graph showing correlation between amount of sevoflurane (ml) consumed weight|
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The mean volume of liquid sevoflurane consumed was found to be 6.4040 ± 2.109 ml, the mean volume of sevoflurane consumed on per minute basis of procedure was found to be 0.6267 ± 0.2865 ml/min. The median value for the same was 0.6014 ml/min. Four patients required much higher values of sevoflurane/min [Figure 3]. Total sevoflurane consumed was comparable in males and females [Figure 4]. Mean sevoflurane consumption among males and females was 6.258 ± 2.148 and 6.663 ± 2.043 ml, respectively. The means were compared using unpaired student t test, and the difference was found to be statistically non-significant (−0.405 ± 0.439, P = 0.359). The cost of sevoflurane consumed per minute of procedure was found to be Rs. 13.23, and the average cost of each procedure was Rs. 140.80.
|Figure 3: Box and Whisker graph showing cost per minute of EUA; 4 patients (circles) showing deviation from normal 95 percentile range|
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|Figure 4: Box and Whiskers graph showing comparison between usage in males versus females|
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| Discussion|| |
Use of any drug should not only be guided by its clinical profile but also should be justified on "cost benefit ratio" basis. Introduction of newer inhalation agents in anesthesia practices have been evaluated on safety basis. The studies documenting their superiority to previous generation agents keep emerging. However, the pharmaco-economics of these agents has almost been completely neglected. The present study aimed to consider factors influencing the price paid for clinical up gradation to this safe anesthetic agent.
The aim of our present evaluation was to find the cost associated with anesthesia during short procedures (induction + maintenance) that are done routinely in most pediatric centers. The cost of induction and maintenance using sevoflurane depends on multiple factors. Use of additional intravenous drugs like opioids lowers the MAC requirements of inhalation agent, thus bringing down the amount of sevoflurane consumed. In the present study, the choice of procedures was limited to EUA, as most of these procedures are purely observational and no additional supplementation of intravenous opioids is required for them. Use of additional nitrous oxide would add to the MAC of sevoflurane and, thus, lower its requirements. The cost of nitrous oxide when compared to sevoflurane is negligible, hence procedures using nitrous oxide are bound to consume less of sevoflurane and are likely to be cheaper. The amount of sevoflurane used in induction is likely to be significantly high (as it is used in high concentration and at high flows); therefore, in the present study, we evaluated only children who underwent inhalation induction. In the maintenance phase, we used a flow of 2 l, as safety concerns due to sevoflurane interaction with soda lime below these flows have been reported. , Also, in a spontaneously breathing child, lower flows can lead to re-breathing, thus flows lower than 2 l are avoided. ,
Six patients in the analysis showed extremely high cost per minute for sevoflurane. These patients either (four of six) required LMA insertion twice or (two of six) had a difficult intravenous cannulation. During the above procedures, the total flow was 6 l, and sevoflurane dial concentration was 4%; this accounted for higher sevoflurane consumption found in these patients. We did not discard the data from these patients, as these are common situations encountered in pediatric settings. The values of mean consumption of sevoflurane would represent these common situations as well. We included the median value of sevoflurane consumption per minute in our analysis, as median would not be representative of these values and would only highlight the cost without unexpected complications.
The results of the present study will be useful in the economic planning of anesthesia-related expenditure. In hospitals charging on per patient basis for a procedure like EUA, the estimated cost would quantify patient charges more appropriately. Also, the results can be used to calculate the estimated number of cases using the sevoflurane stock. If the number of cases calculated and actually done vary significantly, excessive wastage of agent can be suspected. Moreover, cost-based estimates can help calculate the funds to be attributed toward inhalation agents.
For intravenous anesthetic drugs, the amount of drug consumed either depends upon weight or body surface area. In other words, the cost of a drug has a strong direct relation to ideal weight and body surface area. ,, However, the literature on relation of weight or age to the amount of inhalation agent consumed for similar procedures is scarce. It is logical that a heavier child will consume more intravenous drug, but this relation is not true for inhalation agents. The present study showed that there is no statistically significant relation of weight to the amount of sevoflurane used. To eliminate the bias of variable duration of procedures, we calculated sevoflurane consumption per minute; its correlate to weight was still non-significant. Theoretically, the uptake of anesthetic agent can be predicted using Lowe's formula. 
Uptake = 1.3 (MAC/100) × 2 λQ/r
Where, λ is blood gas solubility co-efficient, Q is cardiac output in liters per minute, and r is the ratio of vapor volume at 37° to liquid agent. All factors in the above equation, except cardiac output and MAC, are constant. Cardiac output is related to weight by the equation.
Q = Constant × weight−1/4 .  In other words, for cardiac output to be twice the weight, it must be at least 16 times, however, such a variation in weight is unlikely to exist between the age group in the present study. The maximum and minimum weights of patients in the present study were 5.5 kg and 23 kg, respectively, and 50 patients had a weight that was between 9 and 12 kg, with such a small variation in the weight, the variation in cardiac output would be further smaller and thus variations in requirements were very small. Also, it must be noted that the measured amount of sevoflurane is the value that was delivered to the lungs, of which the above uptake amount is an extremely small fraction.  This means that any difference of uptake, even if present, would make an extremely small difference in the requirement of the inhalation agent being delivered. This possibly explains that we were unable to find any significant correlation between weight and the amount of sevoflurane (cost of sevoflurane) in our patients.
Any significant relation of cost and age of the patient also could not be demonstrated, which holds true with the above Lowe's Equation, as the cardiac output variation among patients relating to age groups between 1 and 8 years is bound to be small.  This difference is further attenuated by the fourth power of cardiac output variable. Our study found no gender differences in consumption or costs of per minute anesthesia. The possible gender difference is attributed to different body fat content. The total body fat content influences the total amount of sevoflurane uptake. , However, the gender differences among body fat contents at pediatric age groups is negligible, these values attain significant values after puberty.  Thus, in the age group of the present study, no significant association could be found.
The duration of procedure showed a linear correlation to the cost. This is an expected result and is also supported by Dion's equation, which shows that the total sevoflurane consumed is directly proportional to time.
The limitation of the present study is that EUA is a short procedure, differences due to body fat composition may become more evident after longer duration of general anesthesia when the fat reserves start to uptake anesthetic agent after high flow organs.  On the basis of the compartment model of inhalation, anesthetic pharmacokinetics when this fat uptake would occur when the EUA would already be over. Also, the study could have been made more accurate if depth of anesthesia monitoring had been used to more accurately titrate the use of sevoflurane to a specific BIS value in each case.
| References|| |
|1.||Dion P. The cost of anaesthetic vapours. Can J Anaesth 1992;39:633. |
|2.||Goa KL, Noble S, Spencer CM. Sevoflurane in paediatric anaesthesia: A review. Paediatr Drugs 1999;1:127-53. |
|3.||Smith I, Nathanson M, White PF. Sevoflurane: A long-awaited volatile anaesthetic. Br J Anaesth 1996;76:435-45. |
|4.||Adriani J, Griggs T. Rebreathing in pediatric anesthesia: Recommendations and descriptions of improvements in apparatus. Anesthesiology 1953;14:337-47. |
|5.||Frink EJ Jr, Green WB Jr, Brown EA, Malcomson M, Hammond LC, Valencia FG, et al. Compound A concentrations during sevoflurane anesthesia in children. Anesthesiology 1996;84:566-71. |
|6.||Anderson BJ, Meakin GH. Scaling for size: Some implications for paediatric anaesthesia dosing. Paediatr Anaesth 2002;12:205-19. |
|7.||Nathan N, Odin I. Induction of anaesthesia: A guide to drug choice. Drugs 2007;67:701-23. |
|8.||Ingrande J, Lemmens HJ. Dose adjustment of anaesthetics in the morbidly obese. Br J Anaesth 2010;105(Suppl 1):16-23. |
|9.||da Silva JM, Mapleson WW, Vickers MD. Quantitative study of Lowece. DrugsesthesiologyJ Anaesthuptake would start the EUA would already b 1997;79:103-12. |
|10.||George HM. Developmental Pharmacology. In: Holzman RS, Mancuso TJ, Polaner DM, editors. A practical approach to pediatric anesthesia. 1 st ed. Philadelphia: Lippincott Williams and Wilkins; 2008. p. 17-47. |
|11.||Fiserova-Bergerova V, Holaday DA. Uptake and clearance of inhalation anesthetics in man. Drug Metab Rev 1979;9:43-60. |
|12.||Jegier W, Sekelj P, Auld PA, Simpson R, McGregor M. The relation between cardiac outputand body size. Br Heart J 1963;25:425-30. |
|13.||Behne M, Wilke HJ, Harder S. Clinical pharmacokinetics of sevoflurane. Clin Pharmacokinet 1999;36:13-26. |
|14.||Roberts F, Freshwater-Turner D. Pharmacokinetics and anaesthesia. Contin Educ Anaesth Crit Care Pain 2007;7:25-9. |
|15.||Taylor RW, Jones IE, Williams SM, Goulding A. Body fat percentages measured by dual-energy X-ray absorptiometry corresponding to recently recommended body mass index cutoffs for overweight and obesity in children and adolescents aged 3-18 y. Am J Clin Nutr 2002;76:1416-21. |
|16.||Lerou JG, Verheijen R, Booij LH. Model-based administration of inhalation anaesthesia. 4. Applying the system model. Br J Anaesth 2002;88:175-83. |
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