J Korean Med Sci.  2016 Jul;31(7):1150-1159. 10.3346/jkms.2016.31.7.1150.

The Anion Gap is a Predictive Clinical Marker for Death in Patients with Acute Pesticide Intoxication

• Lee SH
• Park S
• Lee JW
• Hwang IW
• Moon HJ
• Kim KH
• Park SY
• Gil HW
• Hong SY

• KMID: 2373737
• DOI: http://doi.org/10.3346/jkms.2016.31.7.1150

Abstract

Pesticide formulation includes solvents (methanol and xylene) and antifreeze (ethylene glycol) whose metabolites are anions such as formic acid, hippuric acid, and oxalate. However, the effect of the anion gap on clinical outcome in acute pesticide intoxication requires clarification. In this prospective study, we compared the anion gap and other parameters between surviving versus deceased patients with acute pesticide intoxication. The following parameters were assessed in 1,058 patients with acute pesticide intoxication: blood chemistry (blood urea nitrogen, creatinine, glucose, lactic acid, liver enzymes, albumin, globulin, and urate), urinalysis (ketone bodies), arterial blood gas analysis, electrolytes (Na+, K+, Cl- HCO3 -, Ca++), pesticide field of use, class, and ingestion amount, clinical outcome (death rate, length of hospital stay, length of intensive care unit stay, and seriousness of toxic symptoms), and the calculated anion gap. Among the 481 patients with a high anion gap, 52.2% had a blood pH in the physiologic range, 35.8% had metabolic acidosis, and 12.1% had acidemia. Age, anion gap, pesticide field of use, pesticide class, seriousness of symptoms (all P < 0.001), and time lag after ingestion (P = 0.048) were significant risk factors for death in univariate analyses. Among these, age, anion gap, and pesticide class were significant risk factors for death in a multiple logistic regression analysis (P < 0.001). In conclusions, high anion gap is a significant risk factor for death, regardless of the accompanying acid-base balance status in patients with acute pesticide intoxication.

Keyword

Acidosis; Pesticides; Biomarkers; Acid-base Equilibrium

MeSH Terms

Acid-Base Equilibrium
Acidosis/etiology
Adolescent
Adult
Aged
Aged, 80 and over
Anions/*chemistry/metabolism
Biomarkers/*chemistry/metabolism
Blood Gas Analysis
Chemically-Induced Disorders/mortality/pathology
Electrolytes/analysis
Female
Humans
Intensive Care Units
Logistic Models
Male
Middle Aged
Odds Ratio
Pesticides/*poisoning
Prospective Studies
Risk Factors
Survival Analysis
Urinalysis
Young Adult
Anions
Biomarkers
Electrolytes
Pesticides

Figure

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  Fig. 1 Total number and death rate of the overall patient sample, by acid-base balance status. Note that the death rate is significantly greater in the metabolic acidosis group compared to the other acid-base balance status groups (P < 0.001).

• 

  Fig. 2 Total number and death rate of patients with a high anion gap, by acid-base balance status. Note that the death rate is significantly greater when the high anion gap is accompanied by metabolic acidosis (P < 0.001).

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  Fig. 3 Odds ratios (ORs) of the significant clinical variables from the multivariable logistic regression analysis. The clinical outcome refers to the death rate. Note that the anion gap is an independent risk factor that predicts death. The ORs, 95% confidence intervals (CIs), and P values for each variable are presented in Table 4. ICU, intensive care unit; WMSCN, Workload Management System for Critical Care Nurses.

• 

  Fig. 4 Relationship of the anion gap with parameters, including blood chemistry and complete blood cell count. Note that there was a significant relationship (P < 0.001) with all of the parameters: plasma levels of protein and albumin, albumin/globulin ratio, serum creatinine levels, hematocrit, hemoglobin, RBC and WBC counts, lactate, uric acid, glucose, and triglycerides.

• 

  Fig. 5 Correlation between serum creatinine and creatine kinase levels. The boxes near the X and Y axes represent the interquartile range (25%–75%). The bar in the boxplot represents the median value. The mean, median, 25%, 75%, minimum, and maximum values are presented in the right table. There was a significant positive correlation (r = 0.324, P < 0.001), between serum creatinine and creatine kinase levels.

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  Fig. 6 Simplified overview of anion production and proposed mechanism of death in acute pesticide intoxication. Arrows indicate the proposed sequence of events. *Not all of the pesticide formulations include all of the additives presented in this figure; †Psychiatric stress is included because all of the subjects committed suicide in a state of agitation.

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