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GENERAL ARTICLES

A Unique Case of Recurrent Asystole Secondary to Paroxysmal Pain of Acute Herpetic Ophthalmicus

From the Geelong Hospital, Victoria, Australia.

Address correspondence and reprint requests to Man-Yiu Cheung, MBBS, 7 Ian St., Balwyn VIC 3103, Australia. Address e-mail to manyiucheung{at}yahoo.com.

	Abstract

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Postherpetic neuralgia is considered to be the most common and debilitating complication of acute herpes zoster and its incidence and duration of symptoms increase with age. We describe an unusual, but life-threatening complication of postherpetic neuralgia. The following case report is the first to describe a patient who developed unexpected asystolic episodes as a result of complicating pain secondary to acute herpetic ophthalmicus. The underlying pathogenesis of her cardiovascular disturbance coinciding with her painful paroxysms is unclear. This uncommon phenomenon may be explained by an exaggerated vasovagal response or even by the oculocardiac reflex rarely observed outside ocular or maxillofacial surgery. Her severe paroxysmal pain and asystole were eventually managed with oxycontin, amitriptyline, gabapentin, and intranasal fentanyl spray.

	Introduction

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Recurrent asystolic episodes have not been reported as a complication of acute herpetic ophthalmicus. Here, we describe a case of recurrent asystole secondary to the paroxysmal pain and its management.

	CASE REPORT

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A 52-yr-old woman presented with a 3-day history of lethargy, nausea and vomiting, pain over the right temporal region, and 1-day history of rash over the first division of the trigeminal nerve. She had a history of non-insulin-dependent diabetes mellitus, hyperlipidemia, and hypertension. Her medications included metformin, glibenclamide, simvastatin, and ramipril. She was evaluated by an ophthalmologist, treated with a 5-day course of IV acyclovir for herpes zoster ophthalmicus, and discharged home with acyclovir eye ointment and oxycodone tablets.

She was readmitted to hospital 9 days after discharge for management of severe paroxysmal neuropathic pain. The rash over the temporal area was largely resolved. She reported a constant burning pain behind her right eye and face associated with severe paroxysmal lancinating pain that would recur up to 10 times a day, each attack lasting several minutes. She was most distressed by the paroxysms.

The patient was given Oxycontin^TM 20 mg bid and IM prn morphine without significant relief. Sodium valproate 200 mg bid was added on Day 2. She was referred to the pain management unit on Day 3 because of lack of analgesic response. Sodium valproate was stopped, and amitriptyline 50 mg nocte and gabapentin 300 mg nocte were prescribed.

The patient’s paroxysmal symptoms failed to show significant improvement with the above regimen. Hence, a systemic infusion of lidocaine (0.5–0.75 mg · kg^–1 · h^–1) was started with monitoring in the Coronary Care Unit. Her baseline electrocardiogram (Fig. 1) was unremarkable and showed no evidence of underlying arrhythmia or conduction disturbance. Episodes of asystole varying from 3 to 22 s (Fig. 2) were captured when she developed intense pain involving her face. These episodes were associated with hypotension and brief period of unconsciousness. The lidocaine infusion was promptly ceased. However, further asystolic episodes continued for 24 h after cessation of the lidocaine infusion. These episodes were all preceded by the patient complaining of severe paroxysmal pain. On most occasions, the rhythm spontaneously reverted to a sinus tachycardia and only twice required atropine.

View larger version (24K): [in this window] [in a new window]   Figure 1. Baseline 12 lead ECG.

View larger version (42K): [in this window] [in a new window]   Figure 2. Twenty-two seconds of asystole recorded on ECG strip (lead II and V1).

The patient was transferred to the intensive care unit on Day 5 because of somnolence and type II respiratory failure secondary to narcosis from escalating doses of opioids (Oxycontin^TM 80 mg bid) and intermittent parental morphine. A precautionary transvenous cardiac pacing wire was inserted and she was paced briefly. Her neurological status improved when long-acting opioids were withheld, and 50 µg IV fentanyl bolus was prescribed to treat her paroxysmal pain. She remained in the intensive care unit for 2 days, and invasive ventilation was avoided.

Increasing gabapentin to a daily dose of 1500 mg resulted in reduction of the frequency and intensity of her paroxysmal pain. Further transient bradycardic episodes continued when she had severe painful paroxysms. Her symptoms were generally better controlled and fewer fentanyl boluses were required.

IV fentanyl bolus was replaced with an intranasal (IN) fentanyl spray (Go Medical Nasal Spray Bottle; model number NSS 000) with a plan that she could receive immediate relief for paroxysmal pain at home. Each nasal bottle contains 4 mL of fentanyl with a standard concentration of 50 µg/mL; each spray delivers 0.18 mL (9 µg) of fentanyl. She was instructed to apply two sprays per nostril (36 µg of fentanyl) when experiencing the prodrome of paroxysms. She was managing her paroxysmal pain with the IN spray while she remained as an inpatient, and no further episodes of asystole were observed. Permanent pacing was not required. She was discharged home with the fentanyl IN spray, gabapentin 1500 mg/d, amitriptyline 50 mg nocte, and Oxycontin^TM 20 mg bid. Subsequent follow-up in the Pain Clinic revealed significant improvement of her symptoms; hence, the gabapentin was decreased to 600 mg/d and the IN fentanyl was rarely required.

	DISCUSSION

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Asystole has not been reported as one of the potential complications of acute herpetic ophthalmicus. The pathogenesis of the asystolic episodes after our patient’s severe painful paroxysms is unclear. It could possibly be explained by an exaggerated vasovagal response, a form of oculocardiac reflex or drug interaction of various analgesics.

The vasovagal response can be triggered by stress, prolonged standing, emotion, or severe pain in patients who are predisposed to venous pooling. The sudden decrease in venous return results in a cardiac "hypercontractile" state, which activates mechanoreceptors that normally respond only to stretch. This mimics the condition seen in hypertension and provokes a reflex bradycardia and a further decrease in peripheral vascular resistance (1). However, our patient has no history of syncope, and most of the asystolic episodes occurred while she was staying supine.

The oculocardiac reflex is more commonly seen during surgical manipulation of ocular and periocular structures. The afferent pathway of the reflex arc consists of the trigeminal nerve, which conveys the neuronal signal via the Gasserian ganglion to the sensory nucleus of the trigeminal nerve, whereas the efferent pathway is the vagus nerve, which terminates on the myocardium (2). Stimulation of the trigeminal nerve would result in a vasodepressor effect of sudden onset of bradycardia, asystole, and hypotension. Acute inflammation and neuronal destruction secondary to the reactivation of dormant varicella zoster virus at the affected sensory ganglion and its associated sensory nerve was believed to be the underlying cause of acute herpes zoster (AHZ) pain (3). Hypothetically, noxious neuronal signals travel along the afferent pathway of the oculocardiac reflex arc and may act as potent nonmechanical stimulus, causing the reflex bradyarrhythmia and asystole.

Other factors that might have predisposed our patient to recurrent bradyarrhythmia include undiagnosed myocardial microvascular disease secondary to diabetes and the potential adverse effects from analgesic drugs. Opioids can cause bradycardia via inhibition of central sympathetic output and myocardium conduction pathway. Lidocaine and amitriptyline both cause myocardial Na⁺ channel blockade, which could also induce bradyarrhythmia. Attempts were made to clarify the cause of the asystolic episodes during her management; these included withholding the lidocaine infusion and long-acting opioids. In spite of this, the asystole continued with her paroxysms. The precise mechanism of her recurrent asystole remains unanswered.

AHZ is commonly managed with early institution of antiviral and various analgesic drugs. The primary aim of treating AHZ is to relieve acute pain and minimize the risk of serious complications, such as ocular complications in zoster ophthalmicus and the debilitating postherpetic neuralgia (4). Current effective medical treatment supported by randomized clinical trials for postherpetic neuralgia includes gabapentin, pregabalin, tricyclic antidepressants (TCAs), and opioids (5). Emerging evidence also supports their early use in treating acute herpetic neuralgia (AHN) (6).

Rational polypharmacy is required to control the painful symptoms in AHN. Concurrent use of these drugs can be challenging, especially in the elderly, as adverse drug reactions, drug interactions, and patient tolerability of side effects often limit dosing. A recurrent problem highlighted in this case was medication titration to achieve adequate analgesia and avoid excessive somnolence. Gabapentin, TCAs, and opioids all produce somnolence, which can be exacerbated by combination therapy. Gabapentin and TCAs are effective in alleviating the constant background pain and reducing the frequency of paroxysms, but often a parenterally administered opioid is required to relieve the intense paroxysmal pain and possibly prevent the onset of bradyarrythmia.

We explored the option of using the IN route of opioid delivery to substitute the parenteral (IV) opioid in the predischarge phase from hospital. The IN route avoids first-pass hepatic metabolism, which significantly limits the systemic absorption of lipid soluble opioid orally. Among the opioids, fentanyl has a relatively low molecular weight and high lipid solubility, which allows rapid absorption across nasal mucosal membrane (7). IN fentanyl has a favorable pharmacokinetic profile with a bioavailability of 71% and a rapid onset of peak plasma level of 5 min (8). Furthermore, it does not irritate the nasal mucosa and has low ciliotoxic effects (9). Several randomized control studies comparing IV versus IN fentanyl patient-controlled analgesia for postoperative pain relief demonstrated that IN fentanyl is comparable with IV fentanyl in terms of quality of pain relief, speed of onset, and adverse effects in adult (10–12) and the pediatric population (13). This suggests that fentanyl IN could be an effective alternative to IV administration.

In conclusion, we report recurrent asystole as the unusual, but potentially fatal, complication of AHN. The recurrent asystolic episodes were stopped by targeted treatment of the paroxysmal pain using TCA, gabapentin, and IV/IN fentanyl.

	Footnotes

 
Accepted for publication June 20, 2007.

	REFERENCES

Top Abstract Introduction CASE REPORT DISCUSSION REFERENCES

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Cheung, M.-Y. Articles by Viney, M. Search for Related Content PubMed PubMed Citation Articles by Cheung, M.-Y. Articles by Viney, M. Related Collections Heart Complications Preclinical Pharmacology Pain