Mass methanol poisonings present a serious problem for health systems worldwide, with poor outcome associated with delayed treatment. Positive pre-hospital serum ethanol concentration may have ...predictive value as the prognostic factor of the treatment outcome. We studied the effect of positive serum ethanol level on admission to hospital on survival in patients treated during the Czech methanol outbreak during 2012–2014. Cross-sectional cohort study was performed in 100 hospitalized patients with confirmed methanol poisoning. Pre-hospital ethanol was administered in 42 patients (by paramedic/medical staff to 30 patients and self-administered by 12 patients before admission); 58 patients did not receive pre-hospital ethanol. Forty-two patients had detectable serum ethanol concentration on admission to hospital median 18.3 (IQR 6.6–32.2) mmol dm
−3
. Pre-hospital ethanol administration by paramedic/medical staff had a significant effect on survival without visual and CNS sequelae when adjusted for arterial blood pH on admission (OR 8.73; 95 % CI 3.57–21.34;
p
< 0.001). No patients receiving pre-hospital ethanol died compared with 21 not receiving (
p
< 0.001). Positive serum ethanol concentration on admission to hospital was a predictor for survival without health sequelae when adjusted for arterial blood pH (OR 8.10; 95 % CI 2.85–23.02;
p
< 0.001). The probability of visual and CNS sequelae in survivors reduced with increasing serum ethanol concentration on admission.
Graphical abstract
Context: The influence of co-morbid conditions on the outcome of acute methanol poisoning in mass poisoning outbreaks is not known.
Objective: The objective of this is to study the impact of burden ...of co-morbidities, complications, and methanol-induced brain lesions on hospital, follow-up, and total mortality.
Methods: All patients hospitalized with methanol poisoning during a mass poisoning outbreak were followed in a prospective cohort study until death or final follow-up after 6 years. The age-adjusted Charlson co-morbidity index (ACCI) score was calculated for each patient. A multivariate Cox regression model was used to calculate the adjusted hazards ratio (HR) for death. The survival was modeled using the Kaplan-Meier method.
Results: Of 108 patients (mean age with SD 50.9 ± 2.6 years), 24 (54.4 ± 5.9 years) died during hospitalization (mean survival with SD 8 ± 4 days) and 84 (49.9 ± 3.0 years; p = .159) were discharged, including 27 with methanol-induced brain lesions. Of the discharged patients, 15 (56.3 ± 6.8 years) died during the follow-up (mean survival 37 ± 11 months) and 69 (48.5 ± 3.3 years; p = .044) survived. The hospital mortality was 22%, the follow-up mortality was 18%; the total mortality was 36%. Cardiac/respiratory arrest, acute respiratory failure, multiorgan failure syndrome, and arterial hypotension increased the HR for hospital and total (but not follow-up) mortality after adjustment for age, sex, and arterial pH (all p < .05). All patients who died in the hospital had at least one complication. A higher ACCI score was associated with greater total mortality (HR 1.22; 1.00-1.48 95% CI; p = .046). Of those who died, 35 (90%) had a moderate-to-high ACCI. The Kaplan-Meier curve demonstrated that patients with a high ACCI had greater follow-up mortality compared to ones with low (p = .027) or moderate (p = .020) scores. For the patients who died during follow-up, cancers of different localizations were responsible for 7/15 (47%) of the deaths.
Conclusions: The character and number of complications affected hospital but not follow-up mortality, while the burden of co-morbidities affected follow-up mortality. Methanol-induced brain lesions did not affect follow-up mortality. Relatively high cancer mortality rate may be associated with acute exposure to metabolic formaldehyde produced by methanol oxidation.
2,3,7,8-Tetrachlorodibenzo-
p
-dioxin (TCDD) is highly toxic and affects the cardiovascular system, brain, and skin by AhR-dependent and other mechanisms, as well as causing metabolic impairments and ...cancer. The involvement of the respiratory system has not yet been studied. TCDD in the blood was measured and biomarkers of oxidative stress and inflammation were analysed in 2016 in the exhaled breath condensate (EBC) of the last eight male survivors (mean age 72.4 ± 1.3 years) from 80 workers intoxicated with TCDD during the production of herbicides from 1965 to 1968. The results were compared with their findings in 2010 to evaluate a trend. Malondialdehyde, 4-hydroxy-
trans
-nonenale, and 8-isoprostaglandin F2α (8-isoprostane), in addition to markers of the oxidation of nucleic acids and proteins 8-hydroxy-2-deoxyguanosine, 8-hydroxyguanosine, 5-(hydroxymethyl)uracil,
o
-tyrosine, and 3-nitrotyrosine, as well as markers of inflammation leukotrienes and anti-inflammatory lipoxins, were analysed in EBC by liquid chromatography–electrospray ionisation–tandem mass spectrometry. In addition, the patients underwent chest X-ray, spirometry and fractional exhaled nitric oxide (FeNO) examinations. The control group included 7 men (66 ± 16 years) with comparable lifestyle factors. The median plasma TCDD level lowered from 155 (28–553) ng/kg fat in 2010 to 112 (46–390) ng/kg fat in 2016, i.e., 50 years after exposure. The mean TCDD body deposit was 5.0 ± 3.7 µg. Serum TCDD level in the pooled sample of the controls was 12 ng/kg fat. All markers of oxidative stress, LTB4 and LTC4, remained overexpressed in patients and anti-inflammatory lipoxins were under-expressed compared to controls (all
p
< 0.01). The mean FeNO and spirometry results were within the reference values. Borderline X-ray findings and combined lung function impairments were seen in the patients with the lower TCDD plasma levels. Differences in the expression of the biomolecular markers in EBC as compared to controls were not associated with lung impairments and the respiratory parameters measured. Therefore, these EBC markers can be used to evaluate systemic oxidative stress and inflammation in tissues and the endovascular, atherosclerotic, neurotoxic, and metabolic effects of TCDD.
Graphical abstract
Methyl alcohol intoxications are characterized by high lethality and high prevalence of serious visual and brain damage in survivors. The mechanisms of toxic brain damage are complex and the role of ...carbonyl stress has not been studied yet. We measured the acute and follow-up concentrations of reactive carbonyl compounds in patients with acute methyl alcohol intoxication. Blood samples were collected from 28 subjects hospitalized with confirmed methyl alcohol intoxication and from 36 subjects who survived poisoning 2 years after discharge. Serum concentrations of C
6–12
reactive aldehydes were measured by liquid chromatography–electrospray ionization–tandem mass spectrometry. The acute concentrations of all measured reactive aldehydes were higher than the follow-up concentrations: 36.4 ± 4.8 vs. 21.6 ± 5.2 ng cm
−3
for C
6
; 38.9 ± 5 vs. 17.0 ± 2.0 ng cm
−3
for C
7
; 18.8 ± 3.9 vs. 4 ± 0 cm
−3
for C
8
; 36.5 ± 3.9 vs. 19.0 ± 3.0 ng cm
−3
for C
9
; 6.1 ± 0.4 vs. 4.0 ± 0.5 ng cm
−3
for C
10
; 13.6 ± 3.0 vs. 3.7 ± 0.6 ng cm
−3
for C
11
; and 7.8 ± 0.4 vs. 4.7 ± 0.4 ng cm
−3
for C
12
(all
p
< 0.001). The patients who survived the intoxication had higher concentration of reactive carbonyl compounds than those who died: 38.6 ± 5.9 vs. 28.3 ± 1.7 ng cm
−3
for C
6
(
p
= 0.002); 20.7 ± 4.7 vs. 11.8 ± 1.2 ng cm
−3
for C
8
(
p
= 0.001); 37.7 ± 4.8 vs. 31.8 ± 3.8 ng cm
−3
for C
9
(
p
= 0.042); and 7.9 ± 0.6 vs. 7.3 ± 0.5 ng cm
−3
for C
12
(
p
= 0.022). A significant association was present between severity of metabolic acidosis, anion gap, and the acute concentration of measured biomarkers:
r
= − 0.39;
p
= 0.046 for C
6
;
r
= − 0.42;
p
= 0.035 for C
7
;
r
= − 0.48;
p
= 0.012 for C
8
;
r
= − 0.39;
p
= 0.046 for C
9
; and
r
= − 0.47;
p
= 0.015 for C
11
. The acute concentration of C
6
–C
12
reactive aldehydes positively correlated with the acute serum concentration of leukotrienes (all
p
< 0.05). Acute elevation of serum concentration of reactive carbonyl compounds suggests that carbonyl stress is involved in the mechanisms of leukotriene-mediated neuroinflammatory response to methyl alcohol-induced toxic brain damage.
Graphical abstract
Hydroxocobalamin is an effective first‐line antidote used mainly in monotherapy of cyanide poisonings, while the opinions are different on the effects of its combination with sodium thiosulfate. A ...58‐year‐old male committed a suicide attempt by ingesting of 1200–1500 mg of potassium cyanide; he was unconscious for 1–1.5 min. after ingestion with the episode of generalized seizures. On admission to the ICU, the patient was acidotic (pH 7.28; HCO3 14.0 mmol/L, base excess −12.7 mmol/L, saturation O2 0.999) with high serum lactate (12.5 mmol/L). Hydroxocobalamin was administered 1.5 hr after ingestion in two subsequent intravenous infusions at a total dose of 7.5 g. The infusion was followed by continuous intravenous administration of 1 mL/hr/kg of 10% sodium thiosulfate at a total dose of 12 g. No complications and adverse reactions were registered. Serum lactate decreased to 0.6 mmol/L the same day, and arterial blood gases became normal (pH 7.49; HCO3 27.2 mmol/L, base excess 2.2 mmol/L, saturation O2 0.994). The follow‐up examination 5 months later revealed no damage of basal ganglia and cerebellum on magnetic resonance imaging. The neurological examination revealed no pathological findings. On the ocular coherence tomography, the retinal nerve fibres layer was normal. In visual evoked potentials, there was a normal evoked complex on the left eye and minor decrease in amplitude on the right eye. Combination of hydroxocobalamin and sodium thiosulfate can have a positive effect on the survival without long‐term neurological and visual sequelae in the cases of massive cyanide poisonings due to the possibility of a potentiation or synergism of hydroxocobalamin effects by sodium thiosulfate. This synergism can be explained by the different time‐points of action of two antidotes: the initial and immediate effect of hydroxocobalamin, followed by the delayed, but more persistent effect of sodium thiosulfate.
Context. Visual disturbances due to the toxic effect of formic acid in acute methanol poisonings are generally transient. The subjective symptoms of visual toxicity may resolve within few weeks and ...fundoscopic signs of acute optic neuropathy subside within 1-2 months; therefore, the prevalence of long-term visual sequelae in the population of survivors of poisonings may be underestimated. Objective. To study the prevalence and character of long-term visual sequelae of acute methanol poisonings based on the data from the Czech mass methanol outbreak in 2012. Patients and methods. A total of 50 patients with confirmed methanol poisoning were included in this longitudinal cross-sectional study, median age: 48 (range, 23-73) years. The following tests were performed: optical coherence tomography or OCT with evaluation of the retinal nerve fibers layer (RNFL), visual evoked potentials (VEP), magnetic resonance imaging (MRI) of brain, complete ocular examination (visual acuity/field, color vision, contrast sensitivity, and fundus), neurological examinations, and biochemical tests. Results. Of 50 patients, 7/50 (14%) were discharged with diagnosed visual sequelae and 6/50 (12%) were discharged with both visual and central nervous system sequelae of poisoning. On the follow-up examination, 20/50 (40%) of the patients had long-term visual sequelae, with 8% of blindness. A total of 38% of the patients had abnormal (28% borderline) findings on RNFL, and 40% had abnormal (18% borderline) VEP. Among the patients discharged without detected visual sequelae, 8/37 (22%) had abnormal RNFL and VEP. Patients with visual sequelae had brain lesions more often (70% vs. 27%, p < 0.01). MRI identified optic nerve lesions in 2/20 cases with abnormal VEP only. The groups with and without visual sequelae differed in serum methanol, ethanol, HCO
3-
, formate, pH, anion gap, and base deficit (all p < 0.01). Visual disturbances on admission and coma were more prevalent in the patients with visual sequelae (p < 0.05). Patients with positive serum ethanol on admission were 93% less likely to have optical axonal damage (OR: 0.07 (95% CI: 0.01-0.8); p < 0.05). No association was found between visual sequelae and type of antidote administered, mode of hemodialysis, or folate substitution. Pre-hospital administration of ethanol seemed beneficial: these patients were 90% less likely to have abnormal RNFL findings (OR: 0.10 (95% CI: 0.02-0.52); p < 0.01). Conclusions. The long-term visual sequelae were clearly underestimated on discharge, suggesting a significantly higher amount of patients with long-term sequelae than earlier reported. Thorough examinations before discharge and during follow-up will likely uncover a higher morbidity also after methanol poisonings in general.
•Acute methyl alcohol intoxication leads to an inflammatory response in the brain.•Acute concentrations of IL-4, IL-5, IL-9, IL-10, IL-13, LxA4 and LxB4 were elevated.•The acute elevation did not ...persist suggesting against chronic neuroinflammation.•Association of the follow-up IL-5 concentration with abnormal optic nerve function.•Association of the follow-up IL-10 concentration with brain necrotic lesions.
Methyl alcohol intoxication is a global problem with high mortality and long-term visual sequelae and severe brain damage in survivors. The role of neuroinflammation in the mechanisms of methyl alcohol-induced toxic brain damage has not been well studied. We measured the acute concentrations and dynamics of lipoxins LxA4 and LxB4 and the interleukins IL-4, IL-5, IL-9, IL-10, and IL-13 in the serum of patients treated with methyl alcohol poisoning and the follow-up concentrations in survivors two years after discharge from the hospital. A series of acute measurements was performed in 28 hospitalized patients (mean age 54.2 ± 5.2 years, mean observation time 88 ± 20 h) and the follow-up measurements were performed in 36 subjects who survived poisoning (including 12/28 survivors from the acute group). Visual evoked potentials (VEP) and magnetic resonance imaging of the brain (MRI) were performed to detect long-term visual and brain sequelae of intoxication. The acute concentrations of inflammatory mediators were higher than the follow-up concentrations: LxA4, 62.0 ± 6.0 vs. 30.0 ± 5.0 pg/mL; LxB4, 64.0 ± 7.0 vs. 34.0 ± 4.0 pg/mL; IL-4, 29.0 ± 4.0 vs. 15.0 ± 1.0 pg/mL; IL-5, 30.0 ± 4.0 vs. 13.0 ± 1.0 pg/mL; IL-9, 30.0 ± 4.0 vs. 13.0 ± 1.0 pg/mL; IL-10, 38.0 ± 5.0 vs. 16.0 ± 1.0 pg/mL; IL-13, 35.0 ± 4.0 vs. 14.0 ± 1.0 pg/mL (all p < 0.001). The patients with higher follow-up IL-5 concentration had prolonged latency P1 (r = 0.413; p = 0.033) and lower amplitude N1P1 (r = −0.498; p = 0.010) of VEP. The higher follow-up IL-10 concentration was associated with MRI signs of brain necrotic damage (r = 0.533; p = 0.001) and brain hemorrhage (r = 0.396; p = 0.020). Our findings suggest that neuroinflammation plays an important role in the mechanisms of toxic brain damage in acute methyl alcohol intoxication.
In 1994, a network of small catchments (GEOMON) was established in the Czech Republic to determine input–output element fluxes in semi‐natural forest ecosystems recovering from anthropogenic ...acidification. The network consists from 16 catchments and the primary observations of elements fluxes were complemented by monitoring of biomass stock, element pools in soil and vegetation, and the main water balance components. Over last three decades, reductions of SO2, NOx and NH3 emissions were followed by sulphur (S) and nitrogen (N) deposition reductions of 75% and 30%, respectively. Steeper declines of strong acid anion concentrations compared to cations (Ca, Mg, Na, K, NH4) in precipitation resulted in precipitation pH increase from 4.5 to 5.2 in bulk precipitation and from 4.0 to 5.1 in spruce throughfall. Stream chemistry responded to changes in deposition: S leaching declined. However at majority of catchments soils acted as a net source of S to runoff, delaying recovery. Stream pH increased at acidic streams (pH < 6) and aluminium concentration decreased. Stream nitrate (NO3) concentration declined by 60%, considerably more than N deposition. Stream NO3 concentration was tightly positively related to stream total dissolved nitrogen to total phosphorus (P) ratio, suggesting the role of P availability on N retention. Trends in dissolved organic carbon fluxes responded to both acidification recovery and to runoff temporal variation. An exceptional drought occurred between 2014 and 2019. Over this recent period, streamflow decreased by ≈ 40% on average compared to 1990s, due to the increases of soil evaporation and vegetation transpiration by ≈ 30% and declines in precipitation by ≈ 15% on average across the elevational gradient. Sharp decreases of stream runoff at catchments <650 m a.s.l. corresponded to areas of recent forest decline caused by bark beetle infestation on drought stressed spruce forests. Understanding of the interactions among legacies of acidification and eutrophication, drought effects on the water cycle and forest disturbance dynamics is requisite for effective management of forested ecosystems under anthropogenic influence.
Rapid recovery of precipitation chemistry was followed by steady recovery of acid‐base status at acidic streams (pH < 6) since 1994. Nitrate losses decreased proportionally more than measured declines in N deposition. Drought episodes altered solute fluxes and dissolved organic carbon export. Increased evapotranspiration losses caused dramatic declines in stream runoff at catchments under 650 m a.s.l. Based on documented drought and bark beetle induced forest declines, further alteration of forest biogeochemistry can be expected.
A new hollow-fibre microextraction method has been developed for the determination of a clinical biomarker vanillylmandelic acid (VMA) in human urine. The extraction was used in combination with ...differential pulse voltammetry (DPV) on cathodically pre-treated boron doped diamond electrode (BDDE). Butyl benzoate was found to be the optimum solvent for creation of supported liquid membrane. Optimum donor and acceptor phases were 0.1 mol L−1 HCl and 0.1 mol L−1 NaOH, respectively, optimum extraction time was 30 min. Linear range was from 0.5 to 100 μmol L−1 (r = 0.9989), with good repeatability (RSD 7.9% for 50 μmol L−1 VMA aqueous sample (n = 7)). The limit of detection (LOD) was 0.5 μmol L−1. The method was successfully applied for the determination of VMA in real human urine sample using a standard addition method, obtained RSD being 8.1% (n = 5). The method is sufficiently selective and sensitive for its intended use as a screening tool for elevated concentration of VMA.
Display omitted
•New hollow-fibre microextraction determination of vanillylmandelic acid•Microextraction combined with differential pulse voltammetry•Cathodically pre-treated boron doped diamond working electrode•Environmentally-friendly solvent butyl benzoate as supported liquid membrane•Method verified using real human urine sample
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