Abstract
A case of organophosphate (OP) poisoning was admitted to the emergency room. The patient accepted treatment with pralidoxime (PAM), atropine, and supporting therapy. It was observed that even after 22 h after treatment, 960 mg of atropine was not enough for the patient to be atropinized. However, a 160-mg follow-up treatment of anisodamine was quite enough for atropinization after 4 h. As a case report, more studies are required before any definite conclusion can be reached regarding the use of anisodamine as a potential substitute for high-dose atropine in cases of OP poisoning.
Introduction
Organophosphate (OP) poisoning is an important, life-threatening clinical emergency in rural regions of the developing world. Intentional ingestion of OPs is a common cause of poisoning and is associated with a high mortality rate. 1 Such cases are mainly treated with pralidoxime (PAM) and atropine. The key to successful treatment of OP poisoning is atropinization and the recovery of serum cholinesterase. Both atropine and anisodamine are acetylcholine receptor blockers. By blocking the muscarinic acetylcholine receptor, they can inhibit the hyperexcitability of cholinergic nerves, reduce glandular secretion, eliminate muscarinic symptoms, excite respiratory center, relax the spasm of smooth muscle and accelerate the heartbeat. The use of high doses of atropine in treating OP poisoning has been previously reported. However, there remains a general lack of evidence and consensus on the dosage and anisodamine treatment. 2
Case report
A 46-year-old female presented with OP poisoning in the emergency room of the Second Affiliated Hospital, Guangxi Liuzhou Technical College of Medicine, Liuzhou. She had consumed OP (unknown quantity) at noon, which was found 2 h later. On admission, she showed symptoms of nausea, vomiting, hypersalivation, respiratory distress, confusion, and muscle fasciculation. Her stomach was pumped, and she received 5 mg of intravenous atropine every 5 min as well as 1.0 g of intravenous pralidoxime chloride (PAM-CL). Four hours later when the patient was unconscious, orotracheal intubation was performed. Physical examination revealed a pulse rate of 64 beats/min, blood pressure (BP) of 96/62 mmHg, respiratory rate (RR) of 12 breaths/min, isocoria (diameter of each pupil was 1.5 mm) with slight reaction to light, pale and clammy skin, and pulmonary crackles. Laboratory test results revealed peripheral capillary oxygen saturation (SpO2) levels of 88–94% with a fraction of inspired oxygen (FiO2) of 0.8 in synchronized intermittent mandatory ventilation (SIMV) mode; acetylcholinesterase (AChE) activity of 59% of normal limits; and blood gas (BG) and other blood chemistry values were within normal limits. Emergency management was administered along with preventative antibiotics in cases of aspiration pneumonia and other supportive treatment. Sixteen hours later, the total dose of atropine administered was 600 mg and that of PAM-CL was 2.75 g. Over the next 6 h, 5 mg of atropine was continued to be administered intravenously every 5 min, and infusion with 0.5 g of PAM-CL was also continued. However, her symptoms (nausea, hypersalivation, clammy skin, pulmonary crackles, miosis, and low heart rate) did not improve. At this point, that is, 22 h after admission, the total dose of atropine administered was 960 mg.
It was speculated that the patient was resistant to atropine; so in the follow-up treatment, anisodamine was administered instead of atropine. Four h after the administration of anisodamine, atropinization was realized. The total dose of anisodamine received by the patient was 480 mg (20 mg/10 min, intravenous injection). This was followed by an injection of 10 mg of anisodamine every hour and infusion of 0.5 g PAM-CL. Ventilatory support was also continued (Table 1).
Clinical data on different admission times.
BE: base excess; AChE activity: acteylcholinesterase activity; AST: aspartate aminotransferase; ALT: alanine aminotransferase; GLU: glucose; BUN: blood urea nitrogen; Cr: creatinine; WBC: white blood cell; RBC: red blood cell; PLT: blood platelet; Hb: hemoglobin; PAM-CL: pralidoxime chloride; 654-2: anisodamine.
On day 3, the patient was conscious, alert, and hemodynamically stable. Seventy-two hours after acute intoxication of the patient, anisodamine was sequentially administered at a dose of 20 mg every 6 h for a total of 4 doses. Then, the frequency of anisodamine administration was reduced and finally stopped when muscarinic and nicotinic signs resolved.
On day 5, ventilatory support was discontinued and the trachea was extubated, followed by oxygen delivery via a face mask.
On day 6, the amount of anisodamine, which had been administered for 3 days, was gradually reduced over 24 h and then discontinued. After a serial monitoring of AChE activity for 72 h, the patient was discharged. The total hospital treatment time was 9 days.
Discussion
Treatment of OP poisoning focuses on the reversal of muscarinic signs through atropine administration and enzyme reactivation through pralidoxime administration. Though the effectiveness of oximes in OP poisoning is still under debate, atropine is considered to be a significant cornerstone in the treatment of OP poisoning. Atropine competitively antagonizes acetylcholine at muscarinic receptors to reverse excessive secretions, miosis, bronchospasm, vomiting, diarrhea, diaphoresis, and urinary incontinence. However, there are no data to guide the administration of atropine, so recommendations for atropine dosage vary widely. 3 Total doses of as high as 116,000 mg have previously been reported for the treatment of OP-poisoned patients. 4 Some studies have suggested that there is no therapeutic advantage in overatropinization of these patients. 2 As shown in this case, atropinization was achieved through the administration of a total atropine dose of 960 mg over 22 h with concomitant administration of 480 mg of anisodamine over 4 h. Anisodamine is a kind of acetylcholine receptor-blocking drug with the pharmacological mechanism of atropine. With peripheral anticholinergic effects, it can relax the spasm of smooth muscles and microvascular tissues and improve the rigidity and tremor symptoms. Thus, as a calcium channel blocker, it can inhibit Ca2+ influx. 5 It was unclear why anisodamine brought about atropinization more quickly than atropine. On the one hand, OPs are fat-soluble compounds that can rapidly spread in tissues and easily pass through the blood–brain barrier, allowing them to exert their effects on the central nervous system, 6 and anisodamine has the ability to preferentially interact with acidic membrane phospholipids, which would serve to protect nerve cells. 7 On the other hand, the patient was constitutionally resistant to atropine but was sensitive to anisodamine. Therefore, it is reasonable to believe that a high dose of atropine may not be what is needed when a patient is judged to be atropine resistant. More clinical data are needed to ascertain whether anisodamine can be used in place of high doses of atropine in such patients.
Footnotes
Authors’ Note
This paper has been reviewed and ethically approved by the Second Affiliated Hospital, Guangxi Liuzhou Technical College of Medicine. Written informed consent has been obtained from the patient. This manuscript has not been published elsewhere and is not under consideration for publication elsewhere.
Conflict of Interest
The authors declared no conflicts of interest.
Funding
This study was supported by the National Natural Science Foundation of China (No: 30960130); Guangxi Natural Science Foundation (No: 2012GXNSFAA276011 and No: 2013GXNSFBA019163); and Guangxi Medical University Youth Science Foundation (GXMUYSF201216).