Neurol Med Chir (Tokyo) 50, 339¿342, 2010

Transient Asystole During Surgery for Posterior Fossa Caused by Activation of the Trigeminocardiac Reflex —Three Case Reports—

Kenichi USAMI,KyousukeKAMADA,NaotoKUNII, Hiroko TSUJIHARA*, Yoshitsugu YAMADA*, and Nobuhito SAITO

Departments of Neurosurgery and *Anesthesiology, The University of Tokyo Hospital, Tokyo

Abstract Three patients undergoing surgery for cerebello-pontine angle meningioma suffered transient episodes of asystole. All patients exhibited return to the previous heart rate with cessation of surgical manipula- tions and administration of anticholinergic agents. These reactions were apparently elicited by activa- tion of the trigeminocardiac reflex (TCR) by direct stimulation of the trigeminal nerve or branches in the or . Remifentanil was used in all three cases as an anesthetic agent, so may be a cause of the TCR. The possibility of activation of the TCR should be considered during sur- gical manipulation around the trigeminal nerve or the distribution of the trigeminal nerve branches. Transient bradycardia, hypotension, or asystole can occur regardless of whether there is pressure on the brainstem during posterior fossa meningioma surgery. Key words: trigeminocardiac reflex, posterior fossa meningioma, asystole, remifentanil, bradycardia

Introduction ry lesions.11) In almost all cases, cessation of surgical manipulations or administration of anticholinergic agents Cauterization of the cerebellar tentorium or dura mater of normalized the heart rate, and prevented recurrence of the skull base and detachment of tumor from the cranial TCR without postoperative complications. nerves are routine manipulations in surgery for posterior We describe three cases of transient asystole which oc- fossa meningioma. Transient bradycardia, hypotension, curred during posterior fossa tumor resection. and asystole are rare complications of these manipula- tions, probably arising from excitation of the Case Reports trigeminocardiac reflex (TCR) by direct stimulation of the trigeminal nerve or branches in the dura mater or cerebel- Case 1: A 36-year-old woman presented with sudden onset lar tentorium. of headache at 26 weeks and 2 days of pregnancy. Comput- The TCR results from stimulation of the trigeminal ed tomography (CT) and magnetic resonance (MR) imag- nerve or sensory branches distributed in the cerebellar ing revealed a 5-cm diameter mass in the left cerebello- tentorium, falx, or skull base dura mater which is conduct- pontine angle with intratumoral hemorrhage (Fig. 1A, B). ed to the vagal motor nucleus, which delivers inhibitory After admission, she gradually developed disturbance of stimulation to the heart and systemic vascular system via consciousness, and CT demonstrated slight hydrocepha- the sensory nucleus of the trigeminal nerve in the brain- lus. Her baby was delivered by cesarean section, with stem via various neural circuits.6,10) However, the detailed priority given to the baby's health rather than the mother. pathways of conduction between the trigeminal and vagal Ten days later, suboccipital decompressive craniectomy nervous systems are unclear. Numerous cases of TCR was performed to avoid cerebral herniation. After the sur- have been caused by intracranial manipulation during gery, her hydrocephalus and level of consciousness im- cerebello-pontine or falx meningioma surgery.1,5,12) In ad- proved. One month later, during recovery from the birth, dition, bradycardia, hypotension, and asystole have been endovascular embolization of the tumor feeding artery caused by TCR during craniofacial surgery,7,13) endovascu- was performed prior to tumor resection. No major lar embolization of dural arteriovenous fistulas in the cere- problems occurred during or after embolization. Tumor bellar tentorium,8) and transsphenoidal surgery for pituita- resection was performed under general anesthesia main- tained with propofol, vecuronium, and remifentanil, at 4 Received July 14, 2009; Accepted September 7, 2009 days after embolization. Surgery was begun in the right

339 340 K. Usami et al.

Fig.2 Case2. A,B:T1-weighted magnetic resonance images with gadolinium enhancement revealing a 3-cm diameter mass in the left cerebello-pontine angle. C: Intraoperative photo- Fig. 1 Case 1. A, B: Computed tomography scan (A) and T1- graph and illustration showing cauterization of the cerebellar weighted magnetic resonance image with gadolinium enhance- tentorium at asystole. BP: bipolar coagulator, CH: cerebellar ment (B) revealing a 5-cm diameter mass in the left cerebello- hemisphere, Co: surgical cotton, PB: petrous bone, PV: petrosal pontine angle with intratumoral hemorrhage. C: Intraopera- vein, Sc: suction, T: tentorium, V: trigeminal nerve, VII: facial tive photograph and illustration showing cauterization of the nerve, VIII: acoustic nerve. D: Electrocardiogram at asystole. cerebellar tentorium at asystole. BP: bipolar coagulator, Co: surgical cotton, PB: petrous bone, Sc: suction, Sp: spatula, SPS: , T: tentorium. D: Electrocardiogram at asystole. mediately discontinued, bolus infusion of atropine sulfate 0.5 mg was administered, and her heart rate then returned to that previously present. Although surgical manipula- park bench position. Temporal craniotomy was added to tions were resumed, no subsequent asystoles occurred. the previous suboccipital craniectomy, a portion of the pe- The histological diagnosis of the resected tumor was be- trous bone was excised, the dura mater and cerebellar ten- nign meningioma. No perioperative complications oc- torium were cut open, and then tumor resection was be- curred due to intraoperative asystole. No arrhythmia was gun through a presigmoid approach. noted except during surgery. A short time after initiation of tumor resection, tran- Case 2: A 52-year-old woman presented with headache, sient periods of asystole lasting 3 to 5 seconds occurred dysarthria, and wobbling. MR imaging revealed a 3-cm di- without warning signs during cauterization of the dura ameter mass in the left cerebello-pontine angle (Fig. 2A, mater around the cerebellar tentorium and petrous bone, B). Surgery was performed in the right park bench posi- to which the tumor was attached. After cessation of surgi- tion under general anesthesia maintained with propofol, cal manipulation, her heart rate returned to that present vecuronium, and remifentanil. Tumor resection was be- previously, and then surgical manipulation was resumed. gun through a retrosigmoid approach. The tumor was After most of the tumor had been resected, during cauteri- detached from its origin in the cerebellar tentorium, and zation of the cerebellar tentorium, a further period of the tentorium was cauterized. During this manipulation, asystole lasting approximately 15 seconds abruptly oc- heart rate transiently decreased from 60 beats to 40 beats curred (Fig. 1C, D). All surgical manipulations were im- per minute, but then returned to that previously present.

Neurol Med Chir (Tokyo) 50,April,2010 TCR and Remifentanil 341

tions the heart rate returned to that previously present. The histological diagnosis of the resected tumor was be- nign meningioma. No perioperative complications were caused by the intraoperative asystole. No arrhythmia was noted except during surgery.

Discussion

Our three patients presented with large compressing the brainstem, but asystole occurred during cauterization of the cerebellar tentorium in Cases 1 and 2 and during traction of the trigeminal nerve in Case 3. These reactions appeared to involve the activation of the TCR via manipulation of a dural branch of the trigeminal nerve in Cases 1 and 2, and to direct manipulation of the trigeminal nerve trunk in Case 3. In Case 1, the asystole in the early phase of surgery was almost certainly caused by compression of the brainstem, but little compression of the pons or medulla oblongata was observed. However, asystole and bradycardia also occurred after removal of most of the tumor, which was unlikely to be caused by compression of the brainstem. Moreover, these reactions all occurred during cerebellar tentorium cauterization and manipulation around the trigeminal nerve, so appeared to involve the TCR.

Fig. 3 Case 3. A, B: T1-weighted magnetic resonance images We reviewed 14 patients who underwent cerebello-pon- with gadolinium enhancement revealing a 2.7-cm diameter tine angle meningioma surgery between September 2001 mass reaching Meckel's cave and extending to the right cerebel- and December 2007, and found that intraoperative TCR lopontine angle. C: Electrocardiogram at asystole. was observed in 1 of the 14 patients. Transient bradycardia occurred during manipulation around the in- ternal auditory meatus, although the relationship between After most of the tumor had been resected, during cauteri- the manipulation and TCR was unclear. However, the zation of the cerebellar tentorium around the petrosal previous and the present three cases all involved the use of vein, an approximately 5-second period of asystole abrupt- remifentanil as an anesthetic agent. In the cases without ly occurred (Fig. 2C, D). All surgical manipulations were TCR, fentanyl or dinitrogen monoxide was used as an immediately discontinued, and heart rate then returned to anesthetic agent. that present previously without administration of atropine Use of remifentanil became widespread in Japan from sulfate. Although surgical manipulations were resumed, April 2007. The half-life of remifentanil in the blood is no asystole subsequently occurred. shorter than that of fentanyl, enabling early recovery from The histological diagnosis of the resected tumor was be- anesthesia. Remifentanil does not usually induce nign meningioma. No perioperative complications were postoperative respiratory depression after lengthy surgery caused by the intraoperative asystole. No arrhythmia was since the cumulative effect is lower, and thus can be used noted except during surgery. in high doses to obtain stronger anesthetic effects. Case 3: A 48-year-old man presented with tinnitus. MR Remifentanil caused severe bradycardia or asystole dur- imaging revealed a 2.7-cm diameter mass reaching Meck- ing the induction of anesthesia,2,4) particularly when el's cave and extending to the right cerebellopontine angle patients had taken both beta blocker and calcium an- (Fig. 3A, B). Surgery was performed in the left park bench tagonist agents together,2,9) though such drugs were not position under general anesthesia maintained with used in our 3 patients. TCR has also been reported in cases propofol, vecuronium, and remifentanil. Tumor resection that involved use of fentanyl or dinitrogen monoxide. was begun through a suboccipital retrosigmoid approach. Therefore, we suggest that remifentanil may more easily The tumor was adhered tightly to the trigeminal nerve. induce hypotension or bradycardia than fentanyl or During traction on the tumor for dissection from the dinitrogen monoxide. trigeminal nerve, a 7-second period of asystole abruptly Hypotension, bradycardia, arrhythmia, or asystole asso- occurred (Fig. 3C). All surgical manipulations were imme- ciated with manipulation around the brainstem may be diately discontinued, and the heart rate then returned to caused by compression of the brainstem or stimulation of that present previously. Atropine sulfate 0.5 mg was in- the vagal nerve nucleus, so the surgeon may consider con- fused, and surgical manipulations were continued. After tinued tissue manipulation risky and thus discontinue the most of the tumor had been resected, transient surgery. However, it is important to consider whether the bradycardia occurred during manipulation around the reaction originates from the TCR or brainstem compres- trigeminal nerve, but with cessation of surgical manipula- sion. Any reactions caused by TCR can be expected to

Neurol Med Chir (Tokyo) 50,April,2010 342 K. Usami et al. recover with cessation of all surgical manipulations or ad- 5) Koerbel A, Gharabaghi A, Samii A, Gerganov V, von Gosseln ditional administration of anticholinergic agent, and so H, Tatagiba M, Samii M: Trigeminocardiac reflex during surgical manipulations can be resumed. Bradycardia, skull base surgery: mechanism and management. Acta Neu- hypotension, and asystole induced via the vagus nerve in- rochir (Wien) 147: 727–733, 2005 volve adrenergic transmission, so administration of an- 6) Kumada M, Dampney RA, Reis DJ: The trigeminal depressor response: a novel vasodepressor response originating from ticholinergic agents cannot prevent TCR completely,6) but the trigeminal system. Brain Res 119: 305–326, 1977 cardiovascular complications tend not to linger. However, 7) Lang S, Lanigan DT, van der Wal M: Trigeminocardiac hearing preservation in patients undergoing vestibular reflexes: maxillary and mandibular variants of the schwannoma surgery was worse in the group with in- oculocardiac reflex. Can J Anaesth 38: 757–760, 1991 traoperative TCR compared to the group without TCR.3) 8) Lv X, Li Y, Lv M, Liu A, Zhang J, Wu Z: Trigeminocardiac All neurosurgeons and anesthesiologists should con- reflex in embolization of intracranial dural arteriovenous sider the possibility of induction of the TCR during fistula. AJNR Am J Neuroradiol 28: 1769–1770, 2007 manipulation of the main trunk of the trigeminal nerve, 9) Reid JE, Mirakhur RK: Bradycardia after administration of cerebellar tentorium, falx, or intracranial or extracranial remifentanil. Br J Anaesth 84: 422–423, 2000 courses of the trigeminal nerve. 10) Schaller B: Trigeminocardiac reflex. A clinical phenomenon or a new physiological entity? JNeurol251: 658–665, 2004 11) Schaller B: Trigemino-cardiac reflex during transsphenoidal References surgeryforpituitaryadenomas.Clin Neurol Neurosurg 107: 468–474, 2005 1) Bauer DF, Youkilis A, Schenck C, Turner CR, Thompson 12) Schaller B, Probst R, Strebel S, Gratzl O: Trigeminocardiac BG: The falcine trigeminocardiac reflex: case report and rev- reflex during surgery in the cerebellopontine angle. JNeu- iew of the literature. Surg Neurol 63: 143–148, 2005 rosurg 90: 215–220, 1999 2) DeSouza G, Lewis MC, TerRiet MF: Severe bradycardia af- 13) Stott DG: Reflex bradycardia in facial surgery. Br J Plast Surg ter remifentanil. Anesthesiology 87: 1019–1020, 1997 42: 595–597, 1989 3) Gharabaghi A, Koerbel A, Samii A, Kaminsky J, von Goes- seln H, Tatagiba M, Samii M: The impact of hypotension due to the trigeminocardiac reflex on auditory function in Address reprint requests to: Kenichi Usami, M.D., Department of vestibular schwannoma surgery. J Neurosurg 104: 369–375, Neurosurgery, Faculty of Medicine, The University of 2006 Tokyo, 7–3–1 Hongo, Bunkyo–ku, Tokyo 113–8655, Japan. 4) HiguchiT,MaetaM,IshioY,ShimizuT,TsubakiN,AsaoY: e-mail:usaken-tky＠umin.ac.jp [Asystole after anesthetic induction with remifentanil]. Masui 56: 1339–1342, 2007 (Jpn, with Eng abstract)

Neurol Med Chir (Tokyo) 50,April,2010