Severe neuropsychiatric manifestations and rhabdomyolysis in a patient with imidacloprid poisoning
Correspondence
Severe neuropsychiatric manifestations and rhabdomyolysis in a patient with imidacloprid poisoning
To the Editor,
We read with interest the article bFatal ventricular fibrillation in a patient with acute imidacloprid poisoning,Q wherein the authors report a case of acute imidacloprid intoxication with fatal ventricular fibrillation [1]. Imidaclo- prid is a chloronicotinyl nitroguanide compound developed with the aim of combining high potency against insects with low mammalian toxicity and favorable persistence. Imida- cloprid has been given bcaution-low toxicityQ label for flea eradication, in pest and seed control. However, the current report suggests that this agent may not be as innocuous as reported [1,2]. We also conducted a MEDLINE search with the terms bimidaclopridQ and bchloronicotinyl nitroguanideQ and found 2 previous reports of significant human toxicity. We also report our experience of severe accidental toxicity with imidacloprid.
A 24-year-old male farmer presented with agitation, incoherence, sweating, and breathlessness after inhalation of 17.8% imidacloprid (Crop King, Ravi Organics Limited) while spraying on his farm. He had apparently become unconscious after accidentally inhaling the insecticide spray, further accentuating the exposure. His relatives denied any smoking, alcohol, or substance abuse by the index patient. Examination revealed extreme agitation, frothy secretions, cyanosis, diaphoresis, and disorientation. He was febrile, pulse rate was 132 beats/min, blood pressure was 166/98, and respiratory rate was 36 breaths/min. Chest auscultation revealed bilateral conducted sounds. No seizures or focal neurological findings were noted. Chest radiograph was normal, and arterial blood gases were suggestive of type II respiratory failure. Serum electrolytes and complete blood count were normal. Serum acetyl cholinesterase levels were also normal. Blood, urine, and endotracheal aspirate cultures were sterile. The patient was intubated and mechanically ventilated. Supportive therapy with intravenous fluids, sedation, deep venous thrombosis, and stress ulcer prophy- laxis was also instituted. Extreme agitation despite loraze- pam 8 mg/h necessitated propofol infusion. Haloperidol was
avoided to prevent precipitation of seizures. Propofol was continued at 5 mg kg-1 h-1 to achieve a Richmond score of -1. dark urine developed on the third day of admission. Creatine phosphokinase (total) levels were elevated at 1200 U/L (14-148 U/L) with no evidence of hyperkalemia or elevated serum creatinine. He was managed for rhabdomyolysis with hydration and forced alkaline diuresis. Delirium and weakness persisted until day 6 of illness, after which he was extubated successfully. He was discharged with safety advice on pesticide spraying and is healthy at 2 months follow-up.
Imidacloprid acts as a partial agonist on nicotinyl acetyl choline receptor generating subconductance state currents [3]. Polymorphisms of the a-subunit of the nicotinyl acetyl choline receptor determine the affinity of binding. Our index patient developed severe neuropsychiatric signs with minimal cholinergic features after inhalational exposure to imidacloprid. Hence, it can be surmised therefore that inhalation, in addition to the enteral route, can also result in significant human toxicity, although this is the first report of the same. In addition, given the prominent neurological manifestations, central nicotinic stimulation seems to be the dominant pathogenetic cause. Ninety-six percent of absorbed imidacloprid is reported to be metabolized in 48 hours, mostly by the renal route [4]. The persistence of nicotinic signs beyond 5 days point to multicompartment decay in excretion, with some delay in dissipation of brain toxicity. Rhabdomyolysis might be related to direct nicotinic end-plate stimulation or fever seen in the index patient. In a previous report [1], ventricular fibrillation observed was attributed to either imidacloprid, its diluent (imidacloprid binertsQ), or coexisting coronary artery disease, hypoxia, and hypercarbia. Patients with significant imidacloprid exposure need to be evaluated with high expectation of acute cardiac arrhythmias, autonomic im- balance, rhabdomyolysis, and prolonged neurological tox- icity. During evaluation of our patient, his family members suggested that some agitation, anger, and reduced interac- tion were common in the index patient with some temporal relation to the timing of crop spraying. Clearly, there is an urgent need for higher toxicity rating and accumulation of human data for this compound, especially for subclinical neuropsychiatric effects. The large volumes of imidacloprid
0735-6757/$ - see front matter D 2007
use despite the known effects on pregnant laboratory animals and on DNA adduct formation in the absence of human data are a cause of concern. Future research into antidotes needs to tailor the requirement for high neuro- logical penetration to achieve reversal of intoxication.
Ritesh Agarwal MD, DM Rajagopala Srinivas MBBS, MD Department of Pulmonary Medicine
Postgraduate Institute of Medical Education and Research
Sector-12, Chandigarh 160012, India E-mail addresses: [email protected]
doi:10.1016/j.ajem.2006.11.044
References
- Huang NC, Lin SL, Chou CH, et al. Fatal ventricular fibrillation in a patient with acute imidacloprid poisoning. Am J Emerg Med 2006;7: 883 - 5.
- Wu IW, Lin JL, Cheng ET. Acute poisoning with the neonicotinoid insecticide imidacloprid in N-methyl pyrrolidone. J Toxicol Clin Toxicol 2001;39:617 - 21.
- Ecobichon DJ. Toxic effects of pesticides. In: Klaassen CD, editor. Casarett and Doull’s toxicology. New York7 McGraw Hill; 2001.
p. 763 - 811.
- Cox C. Insecticide factsheet/imidacloprid, Northwest Coalition for Alternatives to Pesticides (NCAP). J Pestic Reform 2001;21: 15 - 21.
PiCCO monitoring accuracy in low body temperature
To the Editor,
transpulmonary thermodilution assumes that the tem- perature within the artery is stable during the measurement period. This condition may not be achieved in clinical practice because of temperature changes that are not solely produced by the thermal indicator; such temperature changes constitute bthermal noise.Q Thermal noise, includ- ing hypothermia and short-term variations in body temper- ature, has been reported to influence the accuracy and reproducibility of thermodilution measurements.
We report the case of a 45-year-old man received from the emergency department (ED) for severe hypothermia after brain trauma, with a body temperature = 248C. The first examination revealed the following: arterial pressure, 70/50 mm Hg; heart rate = 45 beats per minute; coma (Glasgow coma scale 8). He received mechanical ventilation and progressive internal warming. The PiCCO monitoring (Pulsion Medical Systems, Munich, Germany) (triplicate measures) revealed a low cardiac index = 2. 27 L/(min m2), extravascular lung water = 6.1 mL/kg, and intrathoracic blood volume = 740 mL/m2. Afterward, we realized new triplicate measures at each 18 increase in body temperature.
Fig. 1 The COV: b10%, good; 10% V COV V 15%, acceptable. CI indicates cardiac index; ITBVI, intrathoracic blood volume; EVLW, extravascular lung water.
Internal warming increased the body temperature up to 358C in 12 hours. Reproducibility of the PiCCO parameters was assessed by the coefficient of variation (COV= 100% x SD / mean) [1]. According to usual practice, a COV of b10% was considered bgood,Q a COV of 10% to 15% was considered bacceptable,Q and a COV N15% was considered bpoorQ [2]. A total of 36 measurements (12 triplicate measurements) were realized. The COV for cardiac index, intrathoracic blood volume, and extravascular lung water varied, respec- tively, from 17% to 2.4%, 20.4% to 2%, and 15.7% to 3.4%. We noticed that the COV value decreased, whereas the body temperature increased. This may suggest the poor reproduc- ibility of PiCCO thermodilution measurements at low body temperature because of thermal noise (Fig. 1).
Thermal noise was first described with pulmonary arterial catheter [3,4]. Latson et al [5] have concluded that Respiratory variations in pulmonary artery blood tempera- ture are transiently increased in many patients after cardiopulmonary bypass and that this increased thermal noise may cause significant errors in thermodilution cardiac output measurements [5]. Subsequent model calculations demonstrated that the magnitude of potential error in thermodilution cardiac output measurements is dependent on both the amplitude of the respiratory variations in pulmonary artery blood temperature and the baseline cardiac output. On the basis of these thermal area calculations, potential errors of 15% to 50% could be caused by respiratory variations in pulmonary artery blood temperature [5].
With PiCCO monitoring, there are few data. Holm et al
[2] have demonstrated in patients with burn shock and Mild hypothermia a clinically sufficient reproducibility. Martinez- Simon et al [6] reported an erroneous measurement of hemodynamic parameters by PiCCO in a critically ill patient with renal replacement therapy. In our case, the accuracy of PiCCO parameters seems to be worse at low body temperature (b338C).Conclusion
PiCCO monitoring is a simple device for hemodynamic monitoring, but its parameters’ accuracy seems to be affected by body temperature variation (thermal noise).