New Interventional Neuroradiological Procedures in Serbia – The Direct Costs of Classical Neurosurgical Intervention in Relation to the Endovascular Treatment of Intracranial Aneurysms A

Introduction: Intracranial aneurysms are one of the major causes of the neurosurgical morbidity and mortality. Each new therapeutic method, in relation to the standard one, generates high medical costs, as a rule. There have not been estimate of costs of treatment of intracranial aneurysms in Serbia. Objective: The aim of this study was to compare direct medical costs of clipping the neck of the aneurysm in relation to the new neuroradiological technique based on fi lling the aneurysmal sack with platinum coils and/or stenting the neck of the aneurysm. Methods: In a study approved by the Ethics committee of the Belgrade School of Medicine, we retrospectively measured the direct costs of treatment of bleeding and nonbleeding aneurysms at the Clinic of Neurosurgery, Clinical Centre of Serbia (CCS) in 2010. The study included a total of 300 patients divided in two groups: 1) study group included 99 patients with embolized aneurysms and 2) control group included 201 patients who were operated on by classical neurosurgical technique. Direct medical costs were calculated by the methodology of the State Health Care Insurance Fund. Analysis of results was performed using a software package SPSS. Results: Endovascular treatment was associated with 3% of adverse eff ects, lower mortality (2% vs. 2.9%), signifi cantly shorter length of hospital stay (Z = 8.566; p < 0.01), longer duration of anesthesia (226.7 to 195.2 minutes) and signifi cantly higher costs (Z = 12.475; p < 0.01) compared to neurosurgical treatment. A signifi cant diff erence in costs was determined mainly by the price of embolization material, 328,169 RSD per patient (3,111€), and the number of resolved aneurysms (more than one, when the multiple aneurysms were treated).


INTRODUCTION
Th e development of neurosurgery, neurology, and neuroradiology techniques has contributed to the quality of interventional neuroradiological procedures (INRP).Neuroradiological techniques include: computerized tomography (CT), CT angiography (CTA), magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA).
INRP includes: preoperative intravascular embolization of hypervascular tumors of skull base, head and neck (angiomas, glomus, and meningeomas), spinal and paraspinal tumors and treatment of aneurysms, arteriovenous malformations (AVM), arteriovenous dural fi stulas (dAVF) -cranial and spinal.In the multidisciplinary treatment of diseases, anesthesia -as a key factor of clinical support -enabled the performance of diagnostic and therapeutic INRP [1,2].
Clinical Centre of Serbia (CCS) is the largest health facility of tertiary level of care in Serbia.At the Clinic of Neurosurgery, the Section for interventional and invasive neuroradiology has been conducted more than 500 INRP during past decade [3].Th e method has been also applied in Military Medical Academy and Clinical Centers of Kragujevac, Nis and Novi Sad.Amongst all INRPs, since 2007, aneurysm embolization is oft en the most accomplished [3].
According to the statistical data, cerebral aneurysms may be expected in 5% of the population, and 1 -2 % among them will have their aneurysm ruptured with a dramatic clinical picture and consequences [4, 5, and 6].
Today it has been assumed that endovascular treatment, compared to neurosurgical treatment, is better, more modern and less aggressive therapy, associated with low rate of complications, lower mortality, shorter length of hospitalization and lower costs of treatment.From the point of lower costs neurosurgical therapy is preferred over the neuroradiological procedures, and as a rule, newer, more sophisticated methods are more expensive than the standard ones, but the quality of life of patients with aneurysmal SAH is better aft er embolization [7, 8, 9, and 10].
Th e incidence of subarachnoid hemorrhage (SAH) aft er rupture of cerebral aneurysm is 10 -14 per 100,000 inhabitants -for one-year period.It is estimated that during the life span, 15 -20 % of all aneurysms will be ruptured.Th e results show that SAH is the cause of death in 30 % of younger patients (mean age 52), in the fi rst 24 hours.Aneurysmal re-bleeding, in the next 4 weeks, without treatment, may be expected in 25 -30 % of all patients [4].Th e mortality rate is 3% for aneurysms embolized aft er acute bleeding.It is lower than in untreated acute bleeding aneurysms [11].
Under the conditions of market economy, each new treatment method has been verifi ed in relation to the previous standard one, testing its utility for the society and availability for patients.Will the new method replace the previous one depends on the health policy makers, their determination, readiness and the limits of resources?Th ere are published economic studies dealing with direct medical costs of the INRP, but in Serbia there were not done before.Economic evaluations of the total cost of illness include direct medical costs: preclinical, diagnostic, therapeutic (embolization or neurosurgical costs) and of rehabilitation, but ignore personnel costs (salaries of doctors and nurses), the costs of treating complications, re-interventions, control examinations (CT, DSA, MRA) and consumption of medications.Indirect costs to society, resulting from the loss of working contribution, during and aft er treatment (disability, retirement, or a lethal outcome), rarely or never have been calculated.Th e eff ectiveness of therapy and effectiveness of procedures (utility) is measured by extending the life span.Adjusted years of life, in relation to quality (quality-adjusted lifeyears -QALY), has been the most commonly used measure of the useful eff ect of therapy (cost utility analysis -CUA).Contemporary endovascular treatment of aneurysms was introduced in 1991 (platinum coil) and, since 1995, has increasingly been applied in Euro-pean Union countries [12].
At the Clinic of Neurosurgery clipping of the aneurysmal neck was the single therapeutical method available until 1985, but since 2006 increasingly more patients have been treated with endovascular treatment of aneurysms -particularly the complex inoperable aneurysms.Today, there have been two trained teams who exert embolization in the neuroradiological section of the Clinic of neurosurgery.Analysis of results was performed using a commercial soft ware package SPSS.

RESULTS
Th ere have been more female patients, mean age 54.02 ± 10.74 y/o, than male ones, mean age 49.02 ± 12.34, and it has been proven statistically signifi cant (p < 0.01) by T-test.
Clinical variables of patients in the study are shown in Table 1.
From the point of diagnosis, therapy Th e complications during the endovascular procedure were presented in 14% of patients (spasm, ischemia, aneurysmal rupture), and amongst them 3% were more severe (thrombosis, dissection of aneurysm) and produced remaining neurological defi cit.We have no relevant information about complications left behind the clipping of the neck of aneurysms.
In the postoperative time, at the Intensive Care Unit, the mortality was 2 % (n = 2) for the investigated group, and 2.9 % (n = 6) for control group.Forasmuch as there is a diff erence in the length of procedure between anesthetic and surgical protocols.In Table 2, the data were presented.and calculated from the anesthetic protocols and the number of patient days in the disease history.
Th ere has been diff erence in the duration of INRP in relation to the neurosurgical intervention, and it has been proven statistically signifi cant (p < 0.0001) by T-test.
Mann-Whitney test demonstrated that there was a statistically signifi cant diff erence in the number of patient days in favor of the control group, where hospitalization was longer by almost 9 days (Z = -8.566,p < 0.01).
Single price of neurosurgical service was 20,810.82RSD, and the price of clip 14,800 RSD [12].Average cost of standard therapy (Table 3.) was: 298,521.00RSD Mediana (range: 140,062.00 to 1,032,234 RSD), but the cost of general anesthesia was not counted.Th e average cost of general anesthesia was 20,123.29 RSD.
Mann-Whitney test demonstrated that there was a statistically signifi cant diff erence in the cost of the intervention, in RSD, between two groups of patients.Z = -12,348; p < 0.01.
Mann-Whitney test demonstrated that there was a statistically signifi cant diff erence in costs between the two groups of patients, in €: Z = -12.475,p < 0.01.

DISCUSSION
Anthropological variables of the patients agree with other studies where the conclusion postulated that females get aneurysmal SAH more oft en than male, middle-aged patients [5. 14].Patients in both groups were 2 -5 years older than patients in these studies, in our opinion according to the better standard of life which postpone the onset of fi rst SAH.
When an aneurysm is diagnosed, by digital subtraction angiography (DSA), the anatomical characteristics of it have to be assessed and a decision is made of the modality of treatment.In the case of acute aneurysm, urgent therapeutic decision has to be made, because the time is an important factor, given the tendency of cerebral arteries vasospasm, increased blood coagulation and further complications.In our study, acute aneurysms were resolved more oft en by neurosurgical treatment (14 % vs. 11 %), in relation to embolization, which has been explained by the defi ciency of embolization material (stent, coil), regarding the restricted and small health budget.
Endovascular treatment was associated with nearly 3% of adverse complications, lower mortality (2 % vs. 2.9 %), shorter length of hospital stay, for more than 8 days (10.84 vs. 19.41)and longer duration of anesthesia (226.72 vs. 195.22 minutes).Th e data on mortality and diff erence in length of hospital stay (8.5 days) are consistent with other studies from European Union countries, in spite of the fact that the average number of hospital days is smaller (4.5 vs. 7.4 days; and 3.4 vs. 10.5 days) [12,16,17].
Costs of single service associated with the INRP are higher for the socially insured patient, more than 2.5 times in relation to the neurosurgical treatment (20,810.82 RSD vs. 56,088.40 RSD).Th e cost is even less favorable for foreign citizens with health insurance.Embolization material participated 88% in total costs.Average, direct costs of aneurysm embolization were 1,245,331 RSD (12,002 €) vs. 351,177 RSD (3,329 €) for neurosurgical treatment.A statistically signifi cant diff erence was determined mainly by the price of embolization material, approximately 328,169 RSD (3,111 €) per patient, and the number of resolved aneurysms (more than one, when the multiple aneurysms were treated).Costs of neurosurgical treatment generally were increased by the cost of treatment in ICU and the number of hospital days.Other studies approximately indicate the same expenditure of funds [17,18].
If the cost of general endotracheal anesthesia (GETA) would have been calculated, the total cost of endovascular treatment would be increased by further 3%, and neurosurgical treatment by 20%, in accordance to a greater number of GETA (99 vs. 201).According to a study in CCS and our previous studies, the cost of GETA increase costs by 10 -20 % [19,20,21].
Multicenter study comparing coiling and clipping of aneurysmal neck, on 2,143 patients, demonstrated that endovascular procedure was better in terms of preventing re-bleeding aft er aneurysmal rupture, with signifi cantly lower morbidity and mortality in relation to the surgical approach [22].Feasibility study of preventive embolization of unruptured aneurysms made the conclusion that for the 50 y/o patients, treatment of aneurysms was cost eff ective regarding both modalities, for all simulations of rupture ranging from 0.3 -5 % per year [6].Regarding the 70 y/o patients, the embolization was not cost-eff ective if the simulated frequency of aneurysmal rupture was less than 1% for male patients, and ≤ 0.5 % for females, per year.Th e risk of formation of new aneurysms had no corresponding eff ect on the study.
Our current analysis demonstrated that the direct costs of the treatment of bleed-ing and non-bleeding aneurysms, resolved by endovascular procedure, were larger in relation to the standard neurosurgical procedure -for the period of hospitalization.
In the economic assessment, the question whether the embolization is more useful, in relation to neurosurgical treatment, if the same amount of resources would be spent?Th e eff ectiveness of both modalities of treatment has to be demonstrated by the saved years of life, and that would help us in assessing the cost-eff ectiveness, which we intend to do in our next study.Endovascular treatment is being developing faster than neurosurgical treatment of cerebral aneurysms.Assessment of endovascular treatment effi ciency is based on the relative utility and cost-eff ectiveness.

CONCLUSION
Endovascular therapy, compared to neurosurgical treatment, has been associated with lower morbidity, mortality and higher price of embolization material, for all ruptured and unruptured aneurysms.High procedural costs stand opposite to fewer hospital days.Endovascular treatment, as an alternative to neurosurgical treatment, should be off ered to all patients as a viable therapeutic option, given specially the treatment of unruptured aneurysms of posterior cerebral circulation.Which strategy would be selected depends on aneurysmal location, its size, relationship of fundus and neck, as well as by the age of patients, their comorbidity, and the technical characteristics of available embolization material.Th e readiness of State Health Care Insurance Fund to bear the costs of new INRP should be confi rmed by the new feasibility study (CUA) of both modalities, for the multi-year period.

Volume 2 •
Number 2 • May 2015 • HOPH and non-bleeding aneurysms at the Clinic of Neurosurgery in the CCS.Th e study included a total of 300 patients divided in two groups: 1) study group included 99 patients with embolized aneurysms, and 2) control group included 201 patients who were operated on by classical neurosurgical technique.Direct medical costs were calculated by the methodology of the State Health Care Insurance Fund.Both procedures were performed under general endotracheal anesthesia (GETA).Th e time of anesthesia registered in anesthesia protocols represents the period of time during that the anesthesiologist is responsible for the patient's vital functions in the angiography theatre.Anesthesia during the intervention includes: introduction, maintaining of anesthesia and emergence from anesthesia.Neuroradiological and surgical time mean the time from the puncture of an artery (mostly right femoral artery), or surgical incision, until defi nite hemostasis of the puncture place or the last stitch of the scalp.Radiological protocols, among other data, record the amount of exposition to radiation, during INRP, what is signifi cant in terms of radiation exposure of patient and the team performing the intervention.

Table 2 .
The

Table 3 .
The average values of direct costs in RSD and € and prognosis, patients of both groups were comparable for anesthetic risk (ASA) and the clinical grading of subarachnoid hemorrhage (Hunt-Hess modifi ed scale).Th e localization of aneurysms, 48 % ACI in the study group, and 42% ACM in the control group, showed a signifi cant diff erence, in accordance with generally accepted areas of indication.Th ere were 14% of acute bleeding aneurysms, resolved by neurosurgical treatment, and 11% were resolved by endovascular interventions.