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Adverse effects of topical papaverine on auditory nerve function

  • Clinical Article
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Abstract

Background

Papaverine hydrochloride is a direct-acting vasodilator used to manage vasospasm during various neurosurgical operations. Transient cranial nerve dysfunction has been described in a few cases with topical papaverine. This study supports previous reports and provides neurophysiological evidence of an adverse effect on the auditory nerve.

Methods

We conducted a retrospective review of 70 consecutive microvascular decompression operations and studied those patients who received topical papaverine for vasospasm. Topical papaverine was used as a direct therapeutic action to manage vasospasm in a total of 11 patients. The timing of papaverine application and ongoing operative events was reviewed relative to changes in neurophysiological recordings. Brainstem auditory evoked potentials (BAEPs) were routinely used to monitor cochlear nerve function during these operations.

Findings

A temporal relationship was found between topical papaverine and BAEP changes leading to complete waveform loss. The average temporal delay between papaverine and the onset of an adverse BAEP change was 5 min. In 10 of 11 patients, BAEP waves II/III–V completely disappeared within 2 to 25 min after papaverine. Eight of these 10 patients had complete loss of BAEP waveforms within 10 min. One patient showed no recovery of later waves and a delayed profound sensorineural hearing loss. The average recovery time of BAEP waveforms to pre-papaverine baseline values was 39 min.

Conclusions

Topical papaverine for the treatment of vasospasm was associated with the onset of a transient disturbance in neurophysiological function of the ascending auditory brainstem pathway. The complete disappearance of BAEP waveforms with a consistent temporal delay suggests a possible adverse effect on the proximal eighth nerve. Recommendations to avoid potential cranial nerve deficits from papaverine are provided.

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Acknowledgement

Disclosure statement

The authors received no financial interest or support in conjunction with this submission.

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Authors and Affiliations

  1. Neuroscience and Spine Institute, Carolinas Medical Center, Charlotte, NC, USA

    Geraldine M. Chadwick, Anthony L. Asher, Craig A. Van Der Veer & Richard J. Pollard

Authors
  1. Geraldine M. Chadwick
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  2. Anthony L. Asher
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  3. Craig A. Van Der Veer
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  4. Richard J. Pollard
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Corresponding author

Correspondence to Geraldine M. Chadwick.

Additional information

Comment

The authors of this retrospective study should be acknowledged for bringing attention of the neurosurgical community to the potential dangers of cisternal and/or topical application of Papaverine.

We share with Geraldine M Chadwick and coworkers the same practical experience. Since our training with Prof Gazi Yasargil in Zurich in the seventies, we have been using local application of Papaverine along and at the end of our surgeries, especially the ones dealing with aneurysms, skull base tumours and microvascular decompression. At the beginning of our experience we tended to widely irrigate the cisterns with Papaverine (at a dilution of 1ml in 10ml of Ringer's solution). We rapidly noticed (not rare) occurrence of side-effects as those mentioned in this well documented article, with the addition of - otherwise unexplained - epileptic focal seizures as soon as the patient awoke. In order to try to explain these harmful effects, as well as the rapid vasodilatation action of the Papaverine, we asked the chemical laboratory to measure the PH of the solution; it was found at 2.8. So, we found logical to hypothesize that a strong and acute acidose effect on vessels and neural tissue are the main agent of vasodilation and of neural (hopefully transient) toxicity. Because of its beneficial effects to prevent ischemia related to vasospastic "reflexes" after manipulating arteries, we did not abandon Papaverine along surgeries, but only used it in limited topical application with some droplets directly and selective put on the targeted vessels under the microscope (ref 2). While performing microvascular decompression at the VIIth - VIIIth cranial nerves, we could observe soon after application of Papaverine same wave depressions as the ones described in this article when Papaverine was used "in excess", but also - conversely- reversal of decrease in amplitude of peak I linked to vasospasm of AICA or labyrinthine artery when applied topically, and saving the patient from hearing loss (ref1).

Marc Sindou

University of Lyon, France

References

1. Polo G, Fisher C, Sindou M, Marneffe V (2004) Brainstem auditory evoked potential monitoring during microvascular decompression for hemifacial spasm: intraoperative brainstem auditory evoked potential changes and warning values to prevent hearing loss. Prospective study in a consecutive series of 84 patients. Neurosurgery 54:97-106

2. Sindou M, Acevedo G(2001) Microvascular decompression of the trigeminal nerve. Operative Tech. Neurosurg. 4: 110-126, 2001

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Chadwick, G.M., Asher, A.L., Van Der Veer, C.A. et al. Adverse effects of topical papaverine on auditory nerve function. Acta Neurochir (Wien) 150, 901–909 (2008). https://doi.org/10.1007/s00701-008-0004-8

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  • DOI: https://doi.org/10.1007/s00701-008-0004-8

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