Mercury Vapour Long-Lasting Exposure: Lymphocyte Muscarinic Receptors as Neurochemical Markers of Accidental Intoxication.

Introduction. Chronic poisoning may result in home setting after mercury (Hg) vapours inhalation from damaged devices. We report a chronic, nonoccupational Hg poisoning due to 10-year indoor exposure to mercury spillage. Case Report. A 72-year-old man with polyneuropathy of suspected toxic origin. At hospitalization, toxicological clinical evaluations confirmed the altered neurological picture documented across the last decade. Periodic blood and urine Hg levels (BHg, UHg) monitoring were performed from admission (t0), until 1 year later (t2), paralleled by blood neurochemical markers assessment, that is, lymphocytes muscarinic receptors (l-MRs). At t0: BHg and UHg were 27 and 1.4 microg/L, respectively (normal values: BHg 1-4.5; UHg 0.1-4.5), associated with l-MRs increase, 185.82 femtomoL/million lymphocytes (normal range: 8.0-16.0). At t1 (two days after DMSA-mobilization test), BHg weak reduction, paralleled by UHg 3.7-fold increase, was measured together with further l-MRs enhancement (205.43 femtomoL/million lymphocytes). At t2 (eight months after two cycles of DMSA chelating therapy ending), gradual improving of clinical manifestations was accompanied by progressive decrease of BHg and UHg (4.0 and 2.8 microg/L, resp.) and peripheral l-MRs neurochemical marker (24.89 femtomoL/million lymphocytes). Conclusion. l-MRs modulatory effect supports their use as peripheral neurochemical marker in Hg poisoning diagnosis and chelation therapy monitoring.

Neurotoxicity of European viperids in Italy: Pavia Poison Control Centre case series 2001-2011.

CONTEXT: Some clinical aspects about neurotoxicity after snakebites by European viper species remain to be elucidated. OBJECTIVE: This observational case series aims to analyze neurological manifestations due to viper envenomation in Italy in order to describe the characteristic of neurotoxicity and to evaluate the clinical response to the antidotic treatment, the outcome, and the influence of individual variability in determining the appearance of neurotoxic effects. MATERIALS AND METHODS: All cases of snakebite referred to Pavia Poison Centre (PPC) presenting peripheral neurotoxic effects from 2001 to 2011 were included. Cases were assessed for time from bite to PPC evaluation, Grade Severity Score (GSS), onset/duration of clinical manifestations, severity/time course of local, non-neurological and neurological effects, and antidotic treatment. RESULTS: Twenty-four were included (age, 3-75 years) and represented on average of 2.2 cases/year (about 5% of total envenomed patients). The mean interval time of PPC evaluation from snakebite was 10.80 ± 19.93 hours. GSS at ED-admission was 0 (1 case), 1 (10 cases), and 2 (13 cases). All patients showed local signs: 41.6%, minor; 58.4%, extensive swelling and necrosis. The main systemic non-neurological effects were as follows: vomiting (86.7%), diarrhea (66.7%), abdominal discomfort (53.3%), and hypotension (20%). Neurotoxic effects were accommodation troubles and diplopia (100%), ptosis (91.7%), ophtalmoplegia (58.3%), dysphagia (20.8%), drowsiness (16.6%), cranial muscle weakness (12.5%), and dyspnea (4.2%). Neurotoxicity was the unique systemic manifestation in 9 cases; in 4 cases, they were associated with only mild local swelling. In 10 patients the onset of neurotoxic effects followed the resolution of systemic non-neurological effects. Antidote was intravenously administered in 19 (79.2%) patients. The mean duration of manifestations in untreated versus treated groups was 53.5 ± 62.91 versus 41.75 ± 21.18 hours (p = 0.68, local effects) and 9.77 ± 3.29 versus 8.25 ± 12.23 hours (p = 0.1, systemic non-neurological effects) and 43.4 ± 14.69 versus 26.58 ± 20.62 hours (p = 0.03, neurotoxic effects). CONCLUSIONS: Neurotoxicity may appear late (11 hours after the bite in 58.3% of cases), in contrast with the data reported in medical literature. Neurotoxic effects have been reversible in all cases and may be the unique systemic manifestation of envenomation. Neurotoxic effects are shorter in treated group. The antidotic treatment of patients considered as GSS 2 only for neurotoxic effects (with mild local effects) may not be necessary. Variable factors such as different amount of venom injected, concentration of PLA2 component, and individual susceptibility may explain the less percentage of patients presenting neurotoxic effects.

Metformin accumulation: lactic acidosis and high plasmatic metformin levels in a retrospective case series of 66 patients on chronic therapy.

OBJECTIVE. The relationship between metformin accumulation and lactate increase is still debated. This observational case series aims to evaluate the correlation of metformin plasma levels with the pH, lactate and creatinine levels, and with the mortality rate in selected patients with metformin accumulation confirmed through metformin plasma concentration detection at hospital admission. MATERIAL AND METHODS. All cases of lactic acidosis (pH, ≤ 7.35; arterial lactate, ≥ 5 mmol/L) related to metformin accumulation (plasma level ≥ 4 mcg/mL) from 2007 to 2011 were retrospectively reviewed. Erroneous ingestion and voluntary overdoses were excluded. Epidemiological, medical history, clinical and laboratory data were evaluated in all cases. RESULTS. Sixty-six patients were included. Thirty-one patients (47%) had contraindication to therapy with metformin. All patients showed severe lactic acidosis (pH, 6.91 ± 0.18; lactate, 14.36 ± 4.90 mmol/L) and acute renal failure (creatinine, 7.24 ± 3.29 mg/dL). The mean metformin plasma concentration was 40.68 ± 27.70 mcg/mL. Metformin plasma concentrations showed a correlation, statistically significant even if not strong, with creatinine (p = 0.002, R = 0.37), pH (p < 0.0001, R = - 0.43) and plasma lactate levels (p = 0.001, R = 0.41). Sixty-two (94%) underwent dialysis. Early mortality (before discharge from ICU) was 26% (17 cases). Lactate and metformin concentrations had mean levels not statistically different in surviving and deceased patients. CONCLUSIONS. Patients on chronic therapy with metformin may develop a mitochondrial-related toxicity that should be considered when patients present with lactic acidosis, renal failure, and frequently, a medical history of gastrointestinal manifestations during the days preceding the hospital admission. The correlation between metformin plasma concentrations and creatinine, pH, and lactate levels seems to be related to the mechanism of action (inhibition of complex I of the mitochondrial respiratory chain) and to the kinetic properties (high distribution volume and low protein binding) of the drug. The relevant early mortality seems not correlated with the levels of metformin or lactates: this could be due to the possible role of concurrent illness even if, such as for the relationships with lactate and creatinine, a more proper toxicological evaluation could be obtained by assessing metformin erythrocyte concentrations instead of the plasmatic ones.

Recurrent tonic-clonic seizures and coma due to ingestion of Type I pyrethroids in a 19-month-old patient.

CONTEXT: Pyrethroids are synthetic pyrethrin analogues that induce sodium-channel depolarization and hyperexcitation. Severe pyrethroid poisoning is manifested by a "Tremor Syndrome" (Type I cyano-agents) or a "Choreoathetosis/Salivation Syndrome" (Type II non cyano-agents). Very few reports of neurotoxic effects caused by Type I pyrethroids ingestion are available, and no human data concerning Type I pyrethroid blood levels in pediatric poisoning are reported in the medical literature. CASE DETAILS: A 19-month-old female patient presented with irritability and inconsolable crying that rapidly worsened to tonic-clonic seizures and coma (GCS 6). On admission vital signs including BP 110/70 mmHg, HR 110 beats/min, and SpO2 98% on room air were normal. Orotracheal intubation, oxygen administration, and midazolam infusion (4 µg/kg/min) were performed. Intravenous thiopental sodium, up to 18 mg/kg/hour, was administered to control convulsions. An inquiry revealed that 9 h before presentation the patient had ingested an unknown amount of an insecticide containing 7% piperonyl-butoxide and a mixture of the Type I pyrethroids bifenthrin (5%) and esbiothrin (3%). Consequently, gastric lavage was performed, followed by administration of activated charcoal and cathartics. On the subsequent 48 h, the patient returned progressively alert; she was extubated on day 4 and discharged asymptomatically 12 days after hospitalization. After 9, 48, and 72 h of ingestion, the plasma levels were 500, 95, and 40 ng/mL for bifenthrin and 1,640, 640, and 165 ng/mL for piperonyl-butoxide respectively. DISCUSSION: This pediatric case showed severe pyrethroid neurotoxicity associated with measurable plasma levels of bifenthrin and piperonyl-butoxide. In pediatric pyrethroid poisoning, coma and seizures may represent the main life-threatening features. First-aid therapy including airway maintenance and control of muscle fasciculation and seizures is of major importance. Benzodiazepines and high-dose thiopental sodium were effective treatments for convulsion.