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Adv Biomed Res 2013,  2:45

The effect of irrigation of intracisternal papaverine on cerebral blood flow in subarachnoid hemorrhage

Department of Neurosurgery, Al Zahra Hospital, Isfahan University Of Medical Science, Isfahan, Iran

Date of Submission24-Jun-2012
Date of Acceptance02-Aug-2012
Date of Web Publication29-Jun-2013

Correspondence Address:
Peiman Rahmani
Department of Neurosurgery, Al Zahra Hospital, Isfahan University Of Medical Science, Isfahan
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Source of Support: This article is obtained from a thesis which was conducted in Isfahan University of Medical Sciences., Conflict of Interest: The authors declare that they have no competing interests.

DOI: 10.4103/2277-9175.114184

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Background: Despite different treatments, cerebral vasospasm is still the most important cause of death in patients after subarachnoid hemorrhage. This study was conducted to explore the effect of intracisternal washing with papaverine on cerebral blood flow.
Materials and Methods: This study was performed on 40 patients and totally 120 arteries in 2010. Then, variations in cerebral blood flow before and after washing with papaverine were measured and analyzed.
Results: Twenty (20) patients with aneurysm of the anterior communicating artery (ACOM) and 20 patients with aneurysm of the middle cerebral artery (MCA) were assessed. Mean blood flow before aneurysm and before washing in ACOM and MCA was 70.68 ± 14.8 cm/s and 65.66 ± 9.3 cm/s, respectively, which reached 23.25 ± 5.17 cm/s and 34.1 ± 4.7 cm/s, respectively after washing (P value = 0.016 and 0.024). Mean blood flow after aneurysm and before washing in ACOM and MCA was 95.12 ± 13.9 cm/s and 67.44 ± 15.16 cm/s, respectively, which reached 35.69 ± 6.2 cm/s and 38.01 ± 8.28 cm/s, respectively after washing (P value = 0.001 and 0.01).
Conclusion: Washing with papaverine significantly reduces cerebral blood flow and relieves vasospasm.

Keywords: Intracisternal washing, papaverine, subarachnoid hemorrhage, vasospasm

How to cite this article:
Sabouri M, Rahmani P, Rezvani M, Nikbakht H, Rafiee A, Torkashvand M, Eshraghi N, Nourian N, Moradi M. The effect of irrigation of intracisternal papaverine on cerebral blood flow in subarachnoid hemorrhage. Adv Biomed Res 2013;2:45

How to cite this URL:
Sabouri M, Rahmani P, Rezvani M, Nikbakht H, Rafiee A, Torkashvand M, Eshraghi N, Nourian N, Moradi M. The effect of irrigation of intracisternal papaverine on cerebral blood flow in subarachnoid hemorrhage. Adv Biomed Res [serial online] 2013 [cited 2020 Apr 4];2:45. Available from:

  Introduction Top

The incidence of subarachnoid hemorrhage (SAH) is estimated to be 6 to 8 people in 100,000 people. One fourth of these patients die within the first 24 h. Mortality rate has been estimated 45% during the first 30 days. [1] Cerebral vasospasm and delayed cerebral ischemia are still among the major causes of mortality and morbidity in patients after SAH. [1],[2],[3],[4] Angiographic vasospasm is detected in 30 to 70% of patients during the first 5 to 14 days after hemorrhage. [5],[6] Among these patients, 50% with detected vasospasm in angiography suffer from delayed cerebral ischemia, of whom 15 to 20% suffer from stroke or die. [7],[8] The pathogenesis of vasospasm involves endogenous spasmogens including oxyhemoglobin and endothelin. These are believed to inhibit nitric oxide (NO) synthetase and subsequently reduce the level of endogenous vasodilators, thereby producing vasospasm. [9],[10] Prophylaxis with nimodipine, hypertension, hypervolemia, and hemodilution (triple-H) have been improved the outcome of the patients, however, they could not completely remove the effects of vasospasm. [11],[12],[13] The use of intravascular papaverine as an alternative treatment for reversible vasospasm is associated with various side effects including hemodynamic instability like bradycardia and hypotension. Some recent studies have pointed that washing aneurysmal arteries and subarachnoid space with papaverine may not have many complications and hemodynamic disorders besides preventing aneurysmal vasospasm. [4] Because of the lack of prospective studies, the present study was conducted with a suitable sample size to examine the effect of washing subarachnoid space on the amount of cerebral blood flow.

  Materials and Methods Top

This study was a clinical trial carried out in Isfahan's Alzahra Hospital in 2010.

The inclusion criterion of the study was as follow:

The patients with cerebral aneurysm

The exclusion criteria of the study were as follows:

The patients whose cerebral aneurism was not confirmed during the operation.

The patients who could not undergo the treatment due to anesthetic issues.

The patients who did not consent to participate in the study.

Sample size: 20 people were enrolled in the study according to compare mean between 2 groups.

Method of sampling: The participants were selected through simple random sampling.

At first, the method and objective of the study were explained to the patients, then, a written consent was taken from the patients in case of their agreement to participate in the study. During the operation and before aneurysmal arteries clamping, 40 mg of papaverine, which was mixed with 20 cc of saline at 35-37°C was infused to the aneurysmal arteries in subarachnoid space of the patients. Prior to washing with papaverine, blood flow velocity was measured by help of arterial ultrasound (DWL2000 Doppler Ultrasound machine) and a (2 mm, 16 MHz) probe was applied with measurement scale of cm/s. The blood flow velocity was also measured 20 min after washing with papaverine using the arterial ultrasound.

Before administration of drug and 20 min after that, blood pressure and pulse of the patients were assessed and the results were recorded.

The statistical paired-test and SPSS18 software were used to compare the blood flow velocity before and after washing.

  Results Top

Mean age (± SD) of the studied patients was 48.02 ± 9.56 years. Among the patients, 14 (35%) people were men and the rest were women. In anterior communicating group (ACOM), 6 (30%) patients were men and in middle cerebral artery (MCA), 8 (40%) patients were men (P0 value = 0.5). Moreover, mean age of the patients in ACOM group and MCA group was 45.50 ± 2.62 years and 50.55 ± 1.56 years, respectively (P value = 0.1), thus, the two groups were identical in terms of age and sex.

In all cases, blood flow velocity was significantly reduced after washing with papaverine. The comparison of blood flow velocity before and after papaverine infusion is shown in [Table 1] for two groups.
Table 1: Comparison of blood flow velocity before and after papaverine infusion

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There was no significant difference in the reduction of blood flow velocity before and after washing with papaverine in two arteries of ACOM and MCA [Table 2].
Table 2: Comparison of blood flow velocity reduction in the studied branches for the two arteries of ACOM and MCA

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Among the 40 studied patients, 3 (7.5%) of them suffered from bradycardia and 5 (12.5%) of them suffered from hypotension after papaverine infusion. There was no significant difference between the side effects and the aneurysmal artery [Table 3].
Table 3: Comparison of the side effects arising from papaverine for the two groups

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  Discussions Top

Cerebral vasospasm is defined as cerebrovascular angiographic attenuation, which can be symptomatic and asymptomatic. [1] There are different drugs to treat cerebral perfusion pressure which are administrated orally or intra-arterially. While orally administrated, these drugs often do not reach their therapeutic concentration or they need a longer time to act. By intracisternal administration of these drugs, less time is needed to reach the appropriate therapeutic concentration. Papaverine is an alkaloid, which causes vasodilatory induction of cerebral and cardiac vessels through direct effect on the cells of smooth muscles. Mechanism of papaverine effect is the inhibition of cyclic adenosine monophosphate and cyclic guanosine 3 and 5 monophosphate intra-arterially [3] which increase NO and consequently cause the vasodilatory induction. [1] The effect of intra-arterial application of this drug has been sufficiently evaluated, although fewer prospective and controlled trial studies with adequate sample size have been conducted on the effect of intracisternal use of this drug on the vascular tone. Furthermore, intra-arterial injection of papaverine requires neuroradiological intervention and may involve complications. [14]

In this study, papaverine was found to reduce the blood flow velocity significantly in the studied vessels. In a study by Segawa et al., 15 patients with ruptured aneurysm were assessed during operation by washing vessels. Intraoperative serial angiography of 7 patients showed a dilatation in anterior and middle cerebral arteries 30 min after injection of initial dose which lasted 60 min. Neurological symptoms were recovered in 7 patients, however, 6 patients did not show any responses, and the 2 other patients encountered a hematoma. [15] A study published by Kosty (2005) mentioned the vasospasm problem during surgical operations of aneurysms in subarachnoid hemorrhage. The above study explained that despite many studies in this regard, still the actual cause of this phenomenon has not been identified. These researchers pointed to the old therapies for the problem (calcium blockers) and also considered new therapy of papaverine intravascular injection as an effective treatment. They hoped that papaverine intracisternal injection may be effective too, however, it requires further research. [16] In this respect, the present study proved the effect of washing the intracisternal space with papaverine in vasodilatation of vessels with a suitable sample size and examining 120 arteries of 40 patients. Nevertheless, this study did not examine the patients post-operatively and the prevalence of vasospasm in patients and comparing them to the control group. Therefore, this study cannot suggest anything about prophylactic effect of this method for preventing vasospasm, which requires a further study with an adequate sample size and a control group.

The complications of intra-arterial injection of papaverine include mydriasis, confusion, convulsion, reversible depression of brainstem, increase in ICP, hypotension, bradycardia, and thrombocytopenia, [14] and the complications of intracisternal injection of papaverine include mydriasis, seventh nerve palsy, and malignant hyperthermia. [16]

In the study, 7.5% of the patients suffered from temporary bradycardia and 12.5% of them suffered from hypotension, of whom the latter's blood pressure reached a stable condition only by liquid therapy.

  Conclusion Top

It was found that washing intracisternal space with papaverine reduced blood flow velocity in the studied arteries significantly and did not cause serious complication to the patients.

  References Top

1.Ramdurg SR, Suri A, Gupta D, Mewar S, Sharma U, Jagannathan NR, et al. Magnetic resonance imaging evaluation of subarachnoid hemorrhage in rats and the effects of intracisternal injection of papaverine and nitroglycerine in the management of cerebral vasospasm. Neurol India 2010;58:377-83.  Back to cited text no. 1
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2.Firilik KS, Kaufmann AM, Firlik AD, Jungreis CA, Yonas H. Intra-arterial Papaverine for the Treatment of Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage. Surg Neurol 1999;51:66-74.  Back to cited text no. 2
3.Kimball MM, Velat GJ, Hoh BL. Critical Care Guidelines on the Endovascular Management of Cerebral Vasospasm. Neurocrit Care 2011;15:336-41.  Back to cited text no. 3
4.Rath GP, Mukta H, Prabhakar H, Dash HH, Suri A. Haemodynamic changes after intracisternal papaverine instillation during intracranial aneurysmal surgery. Br J Anaesth 2006;97:848-50.  Back to cited text no. 4
5.Fisher CM, Roberson GH, Ojemann RG. Cerebral vasospasm with ruptured saccular aneurysm: The clinical manifestations. Neurosurgery 1977;1:245-8.  Back to cited text no. 5
6.Heros RC, Zervas NT, Varsos V. Cerebral vasospasm after subarachnoid hemorrhage: An update. Ann Neurol 1983;14:599-608.  Back to cited text no. 6
7.Haley EC Jr, Kassell NF, Torner JC. The international cooperative study on the timing of aneurysm surgery. The North American experience. Stroke 1992;23:205-14.  Back to cited text no. 7
8.Longstreth WT Jr, Nelson LM, Koepsell TD, van Belle G. Clinical course of spontaneous subarachnoid hemorrhage: A population-based study in King County, Washington. Neurology 1993;43:712-8.  Back to cited text no. 8
9.Thomas JE, Rosenwasser RH, Armonda RA, Harrop J, Mitchell W, Galaria I. Safety of intrathecal sodium nitroprusside for the treatment and prevention of refractory cerebral vasospasm and ischemia in humans. Stroke 1999;30:1409-16.  Back to cited text no. 9
10.Bagley C. Blood in the cerebrospinal fluid: Resultant functional and organic alterations in the central nervous system. Arch Surg. 1928;17:39-81.  Back to cited text no. 10
11.Kassell NF, Sasaki T, Colohan AR, Nazar G. Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 1985;16:562-72.  Back to cited text no. 11
12.Petruk KC, West M, Mohr G, Weir BK, Benoit BG, Gentili F, et al. Nimodipine treatment in poor grade aneurysm patients. Results of multicenter doubleblind placebo-controlled trial. J Neurosurg 1988;68:505-17.  Back to cited text no. 12
13.Awad IA, Carter LP, Spetzler RF, Medina M, Williams FC Jr. Clinical vasospasm after subarachnoid hemorrhage: Response to hypervolemic hemodilution and arterial hypertension. Stroke 1987;18:365-72.  Back to cited text no. 13
14.Flemming KD, Brown RD Jr, Wiebers DO. Subarachnoid Hemorrhage. Curr Treat option Neurol 1999;1:97-112.  Back to cited text no. 14
15.Segawa H, Saito I, Okada T, Nagayama I, Kitamura K, Takakura K, et al. Efficacy of intracisternal papaverine on symptomatic vasospasm. No Shinkei Geka 1986;14:847-54.  Back to cited text no. 15
16.Kosty T. Cerebral vasospasm after subarachnoid hemorrhage: An update. Crit Care Nurs Q 2005;28:122.  Back to cited text no. 16


  [Table 1], [Table 2], [Table 3]

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