Hydroxychloroquine overdose: A prospective case series

• CORRESPONDENCE

377

FIGURE 2. Serial follow-up brain CT scans. CT scans 2 hours after admission showing redistribution of the ASDH along the cerebellar tentorium (A, arrow), and attenuated brain shift (B). A C T scan 2 days after admission, showing the further attenuation of the brain shift (C).

3. Rockswold GL, Pheley PJ: Patients who talk and deteriorate. Ann Emerg Med 1993;22:1004-1007 4. Kuroiwa T, Tanabe H, Takatsuka H, et al: Rapid spontaneous resolution of acute extradural and subdural hematomas. J Neurosurg 1993;78:126-128 5. Matsuyama T, Shimomura T, Okumura Y, et al: Rapid resolution of symptomatic acute subdural hematoma: case report. Surg Neurol 1997;48:193-196 6. Nagao T, Aoki N, Mizutani H, et al: Acute subdural hematoma with rapid resolution in infancy: case report. Neurosurgery 1986;19: 465-467 7. Polman CH, Gijsbers CJ, Heimans J J, et al: Rapid spontaneous resolution of an acute subdural hematoma. Neurosurgery 1986; 19:446-448 8. Kato N, Tsunoda T, Matsumura A, et al: Rapid spontaneous resolution of acute subdural hematoma occurs by redistribution. Neurol Med Chir (Tokyo) 2001 ;41:140-143

HYDROXYCHLOROQUINE OVERDOSE: A PROSPECTIVE CASE SERIES To the E d i t o r : - - W e read the case report and review of hydroxychloroquine overdose by Marquardt and Albertson 1 with interest. Hydroxychloroquine overdose is rare, but important, particularly with its increasing use for many autoimmune and rheumatological disorders. We would like to describe our unit's experience over the last 13 years. There were 7,245 cases of deliberate self-poisoning that presented to the Hunter Area Toxicology Service (HATS) for the period January 13, 1987 to June 30, 2001. All cases of overdose or poisoning are entered prospectively into a database 2 using a preformatted admission form. 3 There were 6 cases of hydroxychloroquine overdose. The details of these cases are summarized in Table 1.

Copyright 2002, Elsevier Science (USA). All rights reserved. 0735-6757/02/2004-0028535.00/0 doi:l 0.1053/ajem.2002.33775

There were 2 severe cases in the 6. In case 5 the patient presented about 1 hour after taking 14g of hydroxychloroquine. She called the ambulance and opened the door, but became deeply unconscious and developed cardiac arrest within minutes. She was initially treated with bicarbonate, cardioversion, adrenaline (8 nag), magnesium and high dose diazepam (180 mg), and was intubated and ventilated. Her rhythm returned to sinus with a narrowing of the complex from >200 msec to 90 msec, and blood pressure (BP) of 115/85. Despite the use of further inotropes, a total of 1,050 mEq bicarbonate, magnesium, and amiodarone administered while in intensive care, she had progressive widening of the QRS, broad complex arrhythmia, and progressive hypotension. She died 22 hours after admission. Case 4 was the other severe poisoning, with a widened QRS on admission, hypotension and coma (Glasgow Coma Scale [GCS] 5). She survived, but required ventilation in intensive care for 160 hours, and was treated with atropine, intravenous fluids, inotropes, and clonazepam. Although case 1 had a significant poisoning, most of the effects could be explained by the coingestants, in particular the coma was more likely a result of the benzodiazepine taken. She had a normal QRS and was not hypotensive, consistent with a mild hydroxychloroquine overdose. The other 3 cases of hydroxychloroquine poisoning were minor, with no complications. Importantly, all these patients had a normal blood pressure on admission (all between 4 and 5 hours), normal level of consciousness and a normal QRS. This would suggest that after a hydroxychloroquine overdose, all patients with a normal level of consciousness, a normal blood pressure, and a normal QRS are unlikely to have any complications. A larger prospective series is required to confirm this. This series also suggests that 4 g is a potentially life-threatening overdose as shown in case 4. Although both cases 2 and 3 took similar amounts, both had spontaneous emesis before arrival in hospital. This suggests that hydroxychloroquine is of a similar toxicity to chloroquine, where the toxic dose is 20 mg/kg. ~ The onset of action is also as rapid as chloroquine, with both the severe patients presenting within 2 hours with coma and hypotension.

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AMERICAN JOURNAL OF EMERGENCY MEDICINE • Volume 20, Number 4 • July 2002

TABLE 1.

Features of 6 Cases of Hydroxychloroquine Overdose

Case

Age/ Sex

1

16 F

2 3 4

26 M 41 F 47 F

5

29 F

6

16 F

Blood Pressure Dose Medication 1-2 hrs* (g) Coingestants Source 4-5 hrsl ?

Temazepam Paracetamol Codeine 4 Ethanol 3.9 nil 4 nil

14

3.6

Parent

115/451-

Unknown 120/901Other 104/901Own (SLE) 60/-* 110/751-

Ethanol

Own (RA)

88/37* 110/751-

Prednisone Ranitidine

Parent

110/661-

QRS 85

GCS K + 3

90 15 90 15 160 5

>200

3

100 15

-

Complications Nil

ICU

Treatment

36 hrs SDAC V Naloxone NAC 3.4 Nil No SDAC, MDAC Nil 23 hr SDAC, MDAC 2.9 Aspiration pneumonia 160 hr SDAC, Atropine Coma V Clonazepam Hyptension IVF Inotropes 2.0 VF/Broad complex 36 hr SDAC, lavage tachycardia V Cardioversion Hypotension Inotropes Coma Bicarbonate Diazepam (large) IVF Magnesium 3.9 Nil No SDAC

Severity Moderate

Mild Mild Severe

Died

Mild

Abbreviations: SLE, systemic lupus erythematosis; RA, rheumatoid arthritis; V, ventilated; IVF, intravenous fluids; SDAC, single dose activated charcoal; MDAC, multiple dose activated charcoal. NOTE. BP, QRS, and GCS are on admission to hospital *BP at 1-2 hrs; 1-BP at 4-5 hours.

Although only a small case series, the consecutive and prospective nature of the data collection to a single institution, better describes the spectrum of toxicity. The small numbers of cases in the literature and in this 13 year series, means that large, multicenter studies will be required to more comprehensively describe the clinical effects and severity of hydroxychloroquine poisoning, clarify the prognostic features of coma, hypotension and QRS width on presentation and identify the role of different interventions, particularly diazepam. Gastrointestinal decontamination remains a contentious issue, particularly in regards to the timing of activated charcoal. The large trials either excluded severe poisoning or had insufficient numbers of unconscious patients. 4 Thus, there is no evidence to support the suggestion that gastrointestinal tract decontamination should only be used in hydroxychloroquine overdose in the first hour. In paracetamol poisoning it has been shown that activated charcoal given within 2 hours decreases the use of N-acetylcysteine. For agents that have a very low toxicity index, such as hydroxychloroquine, a relatively small decrease in absorption may effect the outcome GEOFFREYK. ISB[STER,BSc, MB BS Department of Clinical Toxicology and Pharmacology Newcastle Mater Hospital Newcastle, Australia Emergency Department Royal Prince Alfred Hospital Sydney, Australia A~aEW DAWSON,MB BS

IAN M. WHYTE,MB BS Department of Clinical Toxicology and Pharmacology Newcastle Mater Hospital Newcastle, Australia University of Newcastle Newcastle, Australia

References 1. Marquardt K, Albertson TE: Treatment of hydroxychloroquine overdose. Am J Emerg Med 2001; 19:420-422 2. Buckley NA, Whyte IM, Dawson AH, et al: Self-poisoning in Newcastle, 1987-1992. Med J Aust 1995; 162:190-193 3. Buckley NA, Whyte IM, Dawson AH, et al: Preformatted admission charts for poisoning admissions facilitate clinical assessment and research. Ann Emerg Med 1999; 34:476-482 4. Whyte IM, Buckley NA: Progress in clinical toxicology: From case reports to toxicoepidemiology. Med J Aust 1995; 163:340-341

GRADUATED COMPRESSIONSTOCKING MANAGESTO PREVENT ECONOMY CLASS SYNDROME To the Editor:--Pathogenesis of economy class syndrome has been denied to be attributed to the occurrence of deep vein thrombosis, ~ but it would be still possible for venous blood to become coagulahle, because a recent study reported that quiet sitting for 2 hours increases blood viscosity and hematocrit (Ht) level locally in the leg not systemically. 2 A standard type of graduated compression stocking has a pressure around 20 mm Hg on the ankle gradually decreasing further up the leg, which compresses the cutaneous veins, shifts some blood to central sites, and increases the deep vein blood flow. 3 These effects prevent venous blood stasis and thrombosis formation, so that compressive therapeutics using the stocking or intermittent pneumatic compression have been achieved widely in the hospitals. 4-7 In this report, the effect of the stocking on prevention for economy class syndrome using a model of 2 hours sitting was examined. After approval of the Institutional Committee, 8 male and 2 female adult healthy volunteers having no history or medications

Copyright 2002, Elsevier Science (USA). All rights reserved. 0735-6757/02/2004-0029535.00/0 doi:l 0.1053/ajem.2002.33772