Article

Acute episode of reversible blindness after an overdose of beta blockers and calcium channel antagonist

Case Report

Acute episode of reversible blindness after an overdose of Beta blockers and calcium channel antagonist

Abstract

Beta-blockers or Calcium channel blockers are major cardiovascular drugs. Both have similar physiologic and toxic effects, and act synergistically. These include refractory bradycardia, heart block, and hypotension. A compromised perfusion of the optic nerve head leads to ischemic optic neuropathy. Two cases of combined beta- blocker and calcium channel blocker overdose causing a previously unknown complication of posterior ischemic optic neuropathy are presented to create awareness so as to make an early recognition of the toxic etiologies, and to introduce appropriate therapy and minimize morbidity.

Beta-blockers (BBs) or calcium channel blockers (CCBs) are prescribed for a variety of medical conditions [1]. Calcium channel blockers directly block entry of calcium through L-type Calcium channels, resulting in arterial smooth Muscle relaxation in vessels. While in the heart, CCBs inhibit depolarization of cells in the sinoatrial and atrioventricular nodes and depress contractility. On the other hand, BBs decrease cyclic AMP cyclic adenosine mono phosphate and decrease flow of calcium through the L-type calcium channels [1]. Thus, Physiologic effects and toxicities of both drugs are similar, and combination of CCBs and BBs has synergistic effects [1].

Ischemic optic neuropathy (ION), a multifactorial disease, is the result of a compromised vascular supply to the intraorbital portion of optic nerve. Nonarteritic anterior or posterior ION (PION) presents with acute painless loss of vision usually in the morning on waking up [2]. Anterior ION is due to involvement of the anterior region of the optic nerve, which is supplied by the posterior ciliary artery [2], whereas PION–a diagnosis of exclusion–is rare and affects the retro laminar optic nerve [2]. In anterior ION, ischemia of the optic nerve produces optic disc edema, whereas with PION, the optic disc is normal and produces no abnormalities on fundoscopy acutely [2]. The absence of optic disc edema is critical in differentiating between these 2 disease processes.

Two cases of PION resulting from an overdose of BB and CCBs taken as a suicidal attempt are presented.

A 55-year-old normotensive and euglycemic female was brought to the emergency department (ED) with a history of ingestion of 30 tablets of verapamil (40 mg) and

35 tablets of metoprolol (50 mg), her husband’s Antihypertensive medications, as a suicidal attempt 4 hours before admission. On examination, she was found to be lethargic and disoriented; her Glasgow coma scale was 8/15. She had no palpable peripheral pulse, and her extremities were cold and clammy. She had bradycardia with an irregular heart rate of 40 to 45 beats/min. Her systolic Blood pressure was 60 mm Hg, whereas the diastolic was not recordable. Because of hemodynamic instability, the patient was electively intubated and mechanically ventilated. Her chest was clear, and the rest of the clinical examination was unremarkable. She was started on 60 g of activated charcoal. Subsequently, 30 g of activated charcoal was continued for the next 36 hours. She was given 2 bolus of normal saline as fluid resuscitation, and it was followed by Calcium gluconate, dopamine, glucagon, insulin, and nor adrenaline infusion to treat the hypotension and bradycardia. With support, the subsequent BP improved to 100/70 mm Hg. A 12-lead electrocardiogram taken in the ED revealed bradycardia with a second-degree Mobitiz type 1 AV block. A 2-dimen- sional echocardiography did not demonstrate any motion abnormalities. Her biochemical and hematological values were within normal limits except low bicarbonate level. ABG Arterial blood gas revealed a wide Anion gap metabolic acidosis with a lactate level of 45. Random Blood sugar was 175 mg/dL. A Transcutaneous pacemaker was used to treat her bradycardia. There was a good capture with a rate of 80 beats/min.

As the patient’s sensorium and hemodynamics improved, she was weaned from the ventilator and off from the pacemaker on day 3 of admission. She was seen using tactile sensation to locate objects on her bedside on day 3. She complained that she could not see anything. Urgent opinion was sought from the ophthalmologist.

The initial ophthalmic examination revealed a visual acuity of perception of light (without projection) in both the eyes. Both her pupils were dilated (6 mm) and nonreacting to light. Fundal examination showed normal optic discs, and there was no evidence of pallor or disc swelling. Visual field analysis and color vision examination could not be

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474.e6 Case Report

conducted due to profound Vision loss. A computed tomography scan of the brain and orbit was unremarkable.

A presumptive diagnosis of PION secondary to an acute episode of hypoperfusion was made based on the history and Ocular examination. medical evaluation revealed no evi- dence of carotid stenosis, thromboembolism, or vasculitis as the cause of ocular ischemia. Supportive measures were carried out with high dose of steroid, but over the subsequent days, her visual acuity improved to counting fingers in both eyes, and she had visual field constriction. Her pupillary reactions recovered slowly. Visual acuity was 6/5 in the right eye and 6/9 in the left eye on discharge, day 10 after her admission. The repeated fundal examination revealed pale discs with sharp margins, and there was no swelling or atrophy but the blood vessels. An ophthalmologic examina- tion six months after the incident revealed that the patient was able to perform her work normally, although patient had bilateral loss of half of the visual field (nasal) with retention of acuity in the other half.

A 25-year-old woman with a history of depression was brought to the ED with a history of ingestion of 25 tablets of verapamil (40 mg) and 20 tablets of metoprolol (50 mg) 1 hour before presentation to the ED. Patient was not a hypertensive, and she had consumed her mother in law’s antihypertensive medications for committing suicide. Patient was on clonozepam (1 mg) and sertalin (50 mg) since the past 6 months for her depression.

On examination, she was distressed and irritable with a pale face; her Glasgow coma scale was 13/15 with an irregular heart rate of 45 to 50 beats/min. Her BP was 90/60 mm Hg. She was started on multidose activated charcoal. A 12-lead electrocardiogram taken at the ED revealed bradycardia with a first-degree AV atrioventricular block. Her biochemical and hematological values were within normal limits. Her ABG, blood glucose, and 2-dimensional echocardiography reports were within normal limits. She was managed conservatively. She improved gradually over 48 hours of admission to the intensive care unit. On the third day, during night, she experienced that the lights became dim and disappeared. When she woke in the morning, she was not able to see.

On examination, both pupils were fixed and dilated, and there was no light perception in either eye. The anterior segments, ocular motility, Intraocular pressures, and fundo- scopy were normal. A working diagnosis of ION was made based on previous experience. Forty-eight hours post- admission, the patient regained light perception in both eyes, and her visual acuity gradually improved with supportive care. At the time of discharge on the eighth postadmission day, her vision recorded at the right eye was 6/12 and left 6/9. The fundal appearance of the blood vessels remained unchanged with diffusely pale optic discs. At follow-up, 6 months after the episode, the patient also had bilateral loss of nasal half of the visual field with retention of acuity in the other half.

An overdose from BB and CCB drugs is a challenging medical emergency with steadily increasing incidence. Beta-

blocker and CCBs affect the L-type calcium channels, thereby causing systemic effects. Metoprolol is a selective beta 1 receptor antagonist without any intrinsic sympatho- mimetic activity. Metoprolol has a higher Lipid solubility and theoretically affects the central nervous system more often than atenolol [1]. Beta-blockers frequently cause first-degree AV block [3] and bradycardia. Verapamil significantly reduces AV nodal conduction more than relaxation. The vascular smooth muscle cells thus has a higher mortality rate than other CCBs [1]. Verapamil overdose usually presents with bradycardia, and AV blocks more often than hypoten- sion [1]. Besides, verapamil reduces pancreatic insulin secretion, thereby causing significant hyperglycemia [1,4]. A combination of verapamil and metoprolol even in the therapeutic range is known to cause Severe bradycardia [5]. Although in toxic range it causes bradycardia, AV block and hypotension [6] were observed in both cases.

Normally, the blood flow to the optic nerve head is maintained at normal levels in spite of variation in perfusion pressures due to autoregulation [2]. However, this auto- regulation works only at certain ranges of perfusion pressures below/above which it breaks down. This auto- regulation is influenced by age, systemic hypertension, arteriosclerosis, ischemic heart disease, diabetes mellitus, and hypercholesterolemia [2]. Moreover, both local and systemic factors influence the ischemia of optic nerve, and different sets of factors influence it in different patients [2]. Transient non/hypoperfusion of the posterior ciliary artery may occur due to shock, surgery, malignant hyper- tension, internal carotid/ophthalmic artery stenosis, glauco- ma, or as a normal phenomenon during sleep–nocturnal arterial hypotension [2,7]. Besides causing systemic hypo- tension, topical BBs and systemic verapamil in normal doses produce marked nocturnal hypotension particularly when taken at bedtime [7]. This fall in blood flow below the level of autoregulation in the patients caused ischemia of the optic nerve head and ION. Interestingly both sys- temic verapamil [8] and topical BBs [9] have been shown to reduce ischemia in the setting of glaucoma, vasospasm,

and embolic episodes.

Because PION should be a diagnosis of exclusion, other causes such as toxicity and drugs were ruled out. In addition, a Visual loss secondary to cortical ischemia would have demonstrated changes on computed tomography and pupil- lary reflex would have been spared. Drugs like ethambutol [10], amiodarone [11], sildenafil, and other phosphodiester- ase inhibitors [12] are known to cause ION. Methanol [13] is the well-known toxic cause of ION like features.

Both drugs are known to cause rhabdomyolysis, renal failure, stroke, myocardial infarction, seizures, and bowel infarction due to hypoperfusion and end organ ischemia [1]. Visual loss after initiation of high-dose Antihypertensive therapy [14] and total blindness due to nifidipine overdose

[15] have been reported earlier.

In the acute overdose setting, CCBs and BBs cause severe hypotension, bradycardia, and conduction blocks. Ischemia

Case Report 474.e7

of end organs results as a squealae, and acute visual disturbance due to ION may result. Although methanol, amiodarone, and ethambutol are widely recognized, BB and CCB overdose appear to be less familiar causes of acute Visual disturbances. Early recognition of the toxic etiologies allows early institution of appropriate therapy aimed at minimizing morbidity and mortality due to these agents.

Subramanian Senthilkumaran MD Namasivayam Balamurgan DM

Sri Gokulam Hospitals and Research Institute

Salem, Tamil Nadu, India E-mail address: [email protected]

Shah Sweni MD

University of Debrecen Medical and Health Science Center

Debrecen, Hungary

Ponniah Thirumalaikolundusubramanian MD

Chennai Medical College and Research Center

Irungalur, Trichy, India

doi:10.1016/j.ajem.2010.04.020

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