pralidoxime and Paralysis

A 33-year-old female ingested an unknown quantity of malathion in a suicide attempt. Cholinergic signs consistent with severe organ, phosphate intoxication developed and were treated within 6 hours of ingestion. Intravenous atropine and a continuous infusion of pralidoxime (400 mg/h) were administered. Prolonged depression of plasma and red blood cell cholinesterases were documented. Despite an initial clinical improvement and the presence of plasma pralidoxime concentrations exceeding 4 microg/mL, the patient developed profound motor paralysis consistent with the diagnosis of Intermediate Syndrome. In addition to the dose and frequency of pralidoxime administration, other factors including persistence of organophosphate in the body, the chemical structure of the ingested organophosphate, and the time elapsed between ingestion and treatment may limit the effectiveness of pralidoxime as an antidote in organophosphate ingestions. This case study suggests that these factors should be taken into account in assessing the risk of Intermediate Syndrome after intentional organophosphate ingestions.

Topics: Adult; Antidotes; Cholinesterase Inhibitors; Cholinesterase Reactivators; Female; Humans; Infusions, Intravenous; Insecticides; Malathion; Paralysis; Pralidoxime Compounds; Syndrome

Seventy two patients admitted to the Intensive Care Unit following ingestion of organophosphorus compounds were studied prospectively with two different doses of pralidoxime (PAM). One group received 1 gm immediately after admission and no further PAM and the other group received infusion of PAM, 1 gm 8 hourly for four days (total 12 gms). The incidence of type II paralysis or intermediate syndrome was 47%. We observed a higher incidence in the 4 days of infusion of PAM group (61%) (20 patients) as compared to the single Bolus dose group (39%) (13 patients). Relative risk 1.48 (confidence interval = 0.9-2.4).

Topics: Adult; Cholinesterase Reactivators; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Drug Overdose; Female; Humans; Infusions, Intravenous; Male; Organophosphate Poisoning; Paralysis; Pralidoxime Compounds; Prospective Studies; Respiratory Paralysis; Syndrome

The ability of galantamine hydrobromide (GAL HBr) treatment to antagonize O-ethyl-S-(2-diisopropylaminoethyl) methylphosphonothiolate (VX)-induced lethality, impairment of muscle tension, and electroencephalographic (EEG) changes was assessed in guinea pigs. Guinea pigs were challenged with 16.8 microg/kg VX (2LD50). One min after challenge, animals were administered 0.5 mg/kg atropine sulfate (ATR) and 25 mg/kg pyridine-2-aldoxime methochloride (2-PAM). In addition, guinea pigs were given 0, 1, 2, 4, 8 or 10 mg/kg GAL as a post-exposure treatment immediately prior to ATR and 2-PAM. Animals were either monitored for 24-h survival, scheduled for electroencephalography (EEG) recording, or euthanized 60 min later for measurement of indirectly-elicited muscle tension in the hemidiaphragm. Post-exposure GAL therapy produced a dose-dependent increase in survival from lethal VX challenge. Optimal clinical benefits were observed in the presence of 10 mg/kg GAL, which led to 100% survival of VX-challenged guinea pigs. Based on muscle physiology studies, GAL post-exposure treatment protected the guinea pig diaphragm, the major effector muscle of respiration, from fatigue, tetanic fade, and muscular paralysis. Protection against the paralyzing effects of VX was dose-dependent. In EEG studies, GAL did not alter seizure onset for all doses tested. At the highest dose tested (10 mg/kg), GAL decreased seizure duration when administered as a post-exposure treatment 1 min after VX. GAL also reduced the high correlation associated between seizure activity and lethality after 2LD50 VX challenge. GAL may have additional benefits both centrally and peripherally that are unrelated to its established mechanism as a reversible acetylcholinesterase inhibitor (AChEI).

Topics: Acetylcholinesterase; Animals; Antidotes; Atropine; Cholinesterase Inhibitors; Cholinesterase Reactivators; Diaphragm; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Electroencephalography; Erythrocytes; Galantamine; Guinea Pigs; Male; Muscle Fatigue; Muscle Tonus; Neurotoxicity Syndromes; Organothiophosphorus Compounds; Paralysis; Phrenic Nerve; Pralidoxime Compounds; Seizures; Time Factors

The authors report 2 cases of organophosphate poisoning which developed intermediate syndrome. The first case was a man who took an organophosphate insecticide, monocrotophos, and developed severe organophosphate poisoning. Respiratory support was needed. He was treated with atropine and 2-PAM. Weakness of neck muscles, proximal limb and respiratory muscle developed in the 3rd day after ingestion. By supportive treatment and careful monitoring, however, he recovered after 11 days of the poisoning. The second case was a lady who took dicrotophos. She developed severe organophosphate poisoning for which respiratory support was also needed High dose of atropine, but without 2-PAM, was administered. She developed bulbar palsy, proximal muscle and respiratory weakness 3 day after the ingestion. Ventilation support was needed for 13 days before weaning was successful. This report did not support an efficacy of pralidoxime (2-PAM) in alleviation of the intermediate syndrome, but aims to alert physicians to recognize the intermediate syndrome for which adequate respiratory care is the crucial key for its management.

Topics: Adult; Atropine; Female; Humans; Insecticides; Male; Muscle Weakness; Organophosphate Poisoning; Paralysis; Pralidoxime Compounds; Respiratory Insufficiency; Syndrome; Thailand; Time Factors

We describe a case of intermediate syndrome after chlorpyrifos ingestion in a toddler, despite a continuous pralidoxime infusion. A 16-month-old girl ingested a pesticide containing chlorpyrifos. She was brought to an Emergency Department where she became lethargic and tachycardic, and subsequently developed pulmonary edema requiring mechanical ventilation. Pralidoxime 150 mg i.v. was administered twice, and an infusion begun at 15 mg/kg/h. At 24.5 h post-ingestion the child had a normal neurologic examination, showed no signs of cholinergic excess, and was extubated successfully. At 27.5 h post-ingestion the child became flaccid, bradycardic and apneic. She was emergently re-intubated. The child's delayed onset of respiratory arrest and flaccid paralysis after an asymptomatic period is consistent with Intermediate Syndrome. This is an unusual case in that it occurred in a young child, was related to chlorpyrifos, and occurred despite continuous and adequate oxime therapy.

Topics: Chlorpyrifos; Cholinesterase Inhibitors; Cholinesterase Reactivators; Female; Humans; Infant; Insecticides; Paralysis; Poisoning; Pralidoxime Compounds; Respiration, Artificial; Respiratory Insufficiency

Poisoning with organophosphate pesticides can cause sensory and motor neuropathy with permanent paralysis. Paralysis at the site of dermal exposure has not been reported.. A 61-year-old carpenter sprayed a nest of termites with an insecticide containing chlorpyrifos without protective equipment and with direct contact of pesticide solution to hands, lower arms, feet, and lower legs, as well as inhalation of vapors from spraying. After 30 min he became ill with nausea, abdominal cramping, arm and leg weakness, bilateral shoulder pain, chest pain, and numbness in the left hand and arm. At a hospital, he was treated with atropine 1 mg IV and pralidoxime Cl 2 g IV There was 0/5 strength in the hands and wrists and 3/5 elsewhere, a left peritoneal palsy, and urinary retention. He was transferred to a tertiary care hospital where paralysis persisted. Electromyogram studies documented widespread peripheral neuropathy. With continued progression of neuropathy, pralidoxime was repeated on the third day. By day 12, motor strength improved except for the hands and left lower leg. Right interosseous muscle strength was 1/5 and left was 0/5. Right-hand grip was 2/5, and left-hand grip was 0/5. He was transferred to a rehabilitation center. He never regained use of his hands and was disabled from employment as a carpenter. There was a disturbed gait, with inability to clear his left foot with walking. Urinary retention persisted and required self-catherization.. Dermal exposure of the hands and feet to chlorpyrifos was associated with atrophy and permanent paralysis of exposed areas. The importance of protective equipment is emphasized.

Topics: Atropine; Chlorpyrifos; Cholinesterase Reactivators; Humans; Insecticides; Male; Middle Aged; Muscarinic Antagonists; Muscle Weakness; Paralysis; Peripheral Nervous System Diseases; Pralidoxime Compounds

Electrophoretic mobility of various analytes can be modeled and thus also predicted using artificial neural networks (ANNs) evaluating experiments done according to a suitable experimental design. In contrast to response surfaces modeling which can be used to predict optimal separation conditions, ANNs combined with experimental design were shown to be efficient for modeling and prediction of optimal separation conditions, while no explicit model and any knowledge of the physicochemical constants is needed. Methodology has been developed and demonstrated on separation of inorganic cations and organic oximes while various additives (methanol, complexation agent), pH or buffer concentration were followed. In our approach proposed the number of experiments necessary to find optimal separation conditions can be reduced significantly.

Topics: Antidotes; Cations; Chemical Warfare Agents; Computer Simulation; Electrophoresis, Capillary; Models, Molecular; Neural Networks, Computer; Oximes; Paralysis; Pralidoxime Compounds

A feral Griffon vulture (Gyps fulvus) was found with tremors, weakness, digit and wing flexion, and an inability to fly. A zero blood cholinesterase activity and a favorable response to treatment with pralidoxime hydrochloride indicated exposure to an anticholinergic pesticide. The bird died after 7 d, and traces of the organophosphate insecticide ethyl parathion were found in the liver and from a blue discolored skin area of the neck. Continuous exposure to ethyl parathion through dermal absorption was presumed the cause of death of the vulture.

Topics: Administration, Cutaneous; Animals; Atropine; Bird Diseases; Birds; Fatal Outcome; Paralysis; Parathion; Pralidoxime Compounds

A case of prolonged succinylcholine-induced paralysis in a child with organophosphate insecticide poisoning is presented. Three hours and 15 minutes of apnea after the administration of succinylcholine was attributed to a decreased rate of succinylcholine metabolism from inhibition of pseudocholinesterase by the insecticide. Only one similar case has been reported previously in the English medical literature. If succinylcholine is to be used in patients with organophosphate poisoning, a prolonged paralysis should be anticipated.

Topics: Apnea; Child, Preschool; Chlorpyrifos; Cholinesterases; Female; Humans; Paralysis; Pralidoxime Compounds; Succinylcholine