Available online at www.sciencedirect.

com

Journal of Acute Medicine 3 (2013) 6e10

www.e-jacme.com

Original Research

Prediction of early mortality in patients with paraquat intoxication

Hsin-Liang Liu a, Wen-Liang Chen b, Mei-Chueh Yang c, Hsiu-Min Lin c,d, Chu-Chung Chou c,e,
Chin-Fu Chang c, Tzeng-Jih Lin a, Kuan-Ting Liu a, Yan-Ren Lin b,c,e,*
a
Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
b
Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan
c
Department of Emergency Medicine, Changhua Christian Hospital, Changhua, Taiwan
d
Department of Nursing, Changhua Christian Hospital, Changhua, Taiwan
e
School of Medicine, Chung Shan Medical University, Taichung, Taiwan
Received 6 October 2012; accepted 9 January 2013
Available online 28 February 2013

Abstract

Objective: Paraquat intoxication has a high mortality rate. The purpose of this study is to identify the clinical features and predictors of early
mortality within 72 hours among individuals with paraquat intoxication in central Taiwan.
Methods: This retrospective study included 92 patients who presented with paraquat intoxication at the emergency department (ED) of a medical
center between January 2004 and December 2009. The patient characteristics, clinical features and outcomes of these patients are presented.
Early mortality was defined as survival of less than 72 hours. The variables and predictors leading to early mortality were also analyzed.
Results: Patients who survived over 72 hours were significantly younger and had ingested less paraquat than those who survived less than 72
hours. Elevated blood creatinine and decreased blood potassium levels in the ED were strong predictors of survival for less than 72 hours. In the
first 12 hours after arriving at the ED, patients with early mortality had higher initial heart rates and mean arterial blood pressures than those who
survived for more than 72 hours. The presence of systemic inflammatory response syndrome, and decreased heart and kidney function were
significantly associated with early mortality (all were p < 0.05).
Conclusion: The presence of systemic inflammatory response syndrome, early tachycardia and renal failure predicted early mortality.
Copyright 2013, Taiwan Society of Emergency Medicine. Published by Elsevier Taiwan LLC. All rights reserved.

Keywords: Early mortality; Paraquat intoxication; Prediction

1. Introduction pulmonary fibrosis with hypoxemia.7e11 However, the clinical

The herbicide paraquat (1,10 -dimethyl-4,40 -bipyridinium
dichloride) has been widely used in many countries since the
mid-1960s, despite the fact that it can be fatal to humans.1e5 The
exact mechanism of toxicity is not completely known, however,
paraquat releases free oxygen radicals (superoxide and hydrogen
peroxide) resulting in damage to different organs.6 High mor-
tality rates, ranging from 33% to 90%, have been reported.3e5
Previous studies have reported that early mortality can occur
within 1e4 days due to multiple organ failure, while delayed
mortality can occur after as long as 3 weeks as a result of
features of patients with severe intoxication followed by early
mortality have not been well addressed. Some studies have
reported that most patients with severe intoxication do not survive
for more than 72 hours.7e11 In this study, we therefore defined
early mortality as death within 72 hours of presentation and aimed
to present the patient characteristics and clinical features asso-
ciated with early mortality in patients with paraquat intoxication.
2. Materials and methods
2.1. Study population and design

* Corresponding author. Department of Emergency Medicine, Changhua We retrospectively reviewed the medical records of patients
Christian Hospital, 135 Nanshsiao Street, Changhua 500, Taiwan. with acute paraquat poisoning who presented to the emergency
E-mail address: h6213.lac@gmail.com (Y.-R. Lin). department (ED) of a 2500-bed medical center in central Taiwan

2211-5587/$ - see front matter Copyright 2013, Taiwan Society of Emergency Medicine. Published by Elsevier Taiwan LLC. All rights reserved.
http://dx.doi.org/10.1016/j.jacme.2013.01.001
 H.-L. Liu et al. / Journal of Acute Medicine 3 (2013) 6e10
from January 2004 to December 2009. The study protocol was
approved by the institutional review board of this hospital. The
information on pesticide intoxication in this patient population
was obtained from the computerized medical record database at
the poison center. Patients with at least one positive finding of
paraquat on tests of urine, gastric juice, and blood were identified
as having paraquat intoxication and were included in our study.
The levels of paraquat were identified by ion exchange chro-
matography and spectrophotometry (Shimadzu UV-160, Shi-
madzu, Milton Keynes, UK). A methyl viologen kit (Sigma
M2254, Kyoto, Japan) was used to detect paraquat.
Patient characteristics and factors possibly associated with the
outcome of paraquat intoxication were recorded and analyzed.
Treatments included the use of activated charcoal, N-acetylcys-
teine, antioxidants, gastric lavage, hemoperfusion, and immu-
nosuppressive agents.12e15 The treatment strategies differed
according to the clinical situation. Patients were classified into
Group 1 if they survived for more than 72 hours or Group 2 if they
for survived less than 72 hours. Clinical features in the two
groups including vital signs, laboratory investigations and radi-
ological examinations of the chest were analyzed. The detailed
hospital records included not only the clinical findings recorded
by the ED doctors and nurses but also histories from family
members. The clinical parameters that fit the criteria of systemic
inflammatory response syndrome (SIRS) were analyzed. The
trends and outcomes of the heart rate and mean arterial pressure
after ED admission were also analyzed between groups.
2.2. Data collection and definitions
Information relating to paraquat exposure was obtained
from medical records and witness statements. All data were
identified and abstracted by ED physicians. Patient data and
predictive factors of survival over 72 hours gathered from the
medical records included:
 gender;
 age at onset;
 occupation (farmer, worker, housekeeper, businessman
and unemployed);
 reason for exposure to poison (accidental or intentional);
 history of suicide attempts;
 whether it was co-ingested with other drugs;
 the amount of poison ingested;
 the period from poison exposure to arrival at the hospital,
paraquat level in the blood;
 vital signs in the ED;
 ED laboratory investigations;
 Apache II score;
 period from poison exposure to oxygen desaturation (pulse
oximeter reading less than 90%);
 radiological evidence of lung injury (radiologist report of
chest radiograph); and
 outcome.
The reason for exposure to the poison was reported by family
members, patients and witnesses. Finally, factors that might be
7
associated with outcome were compared between the two
groups. Initial trends in the heart rate and mean arterial pressure
after arriving in the ED were also compared between groups.
2.3. Statistical analysis
First, descriptive analysis of the data collected that might
change the outcome of the study was performed. Independent
variables (sex, age, occupation, reason for exposure to poison,
history of suicide attempts, co-ingestion with other drugs,
amount of paraquat ingested, period from poison exposure to
arrival at the hospital, vital signs in the ED, clinical ED labora-
tory data, blood paraquat level, urine output in the first 24 hours,
the Apache II score, time from poison exposure to oxygen
desaturation, lung injury status, and duration of survival) are
reported as numbers, percentages, or means  standard de-
viations (SD). Second, head-to-head comparison of these char-
acteristics in Groups 1 and 2 was carried out. Factors possibly
associated with survival over 72 hours were analyzed using the
t test (continuous variables), Fishers exact test, or Chi-square
test. Finally, we used these characteristics (significant variables
predicting survival for over 72 hours) as independent variables to
run the multivariate logistic regression to find risk factors of early
mortality. The variables with univariate comparisons of p < 0.1
were subsequently included in the multivariate logistic regres-
sion analysis (forward selection). A p value <0.05 was consid-
ered statistically significant. All analyses were performed using
SPSS software version 15.0 (SPSS Inc., Chicago, IL, USA).
3. Results
3.1. Patient characteristics
This study identified and enrolled a total of 92 patients with
paraquat intoxication who presented to the ED over 6 years.
Clinical data, initial vital signs, and laboratory data from the
ED are shown in Table 1. Only three (3.3%) patients had been
unintentionally exposed to paraquat (ingestion of a paraquat
solution in an unlabeled bottle). The amount of paraquat
ingested was 100.4  73.7 ml. Fifty-eight (63.0%) patients
survived for more than 72 hours. In all, 62 (67.4%) patients
died during their hospital stay.
3.2. Predictors of survival over 72 hours
Table 2 shows the predictors of survival for over 72 hours in
patients with paraquat intoxication. Patients in group 1 were
significantly younger than those in Group 2 (41.8  16.3 vs.
58.1  15.5 years old, p < 0.001). Group 1 also had a much
lower blood paraquat level than group 2 (1.5  3.4 mg/mL vs.
54.0  97.4 mg/mL, p < 0.001). The SIRS was more promi-
nent in patients who did not survive over 72 hours.
3.3. Logistic regression analysis
After adjusting for factors possibly associated with survival
for over 72 hours, we found that age, a higher creatinine level
8 H.-L. Liu et al. / Journal of Acute Medicine 3 (2013) 6e10

Table 1 4. Discussion
Characteristics and outcomes of patients with paraquat intoxication.
Patients with paraquat In this study, we noted that SIRS was a key factor asso-
intoxication (n 92) ciated with early mortality. The symptoms of SIRS can present
No. % during early ED assessment. The mechanism of paraquat
Patient characteristics toxicity has been investigated and is attributed to redox
Sex cycling that generates superoxide anions leading to the for-
Male 68 73.9 mation of more toxic reactive oxygen and nitrite species.6 The
Female 24 26.1
Age (y) 47.8  17.8
secondary effects of oxidative stress include lipid peroxida-
Occupation tion, mitochondrial toxicity, oxidation of nicotinamide adenine
Farmer 19 20.7 dinucleotide phosphate, apoptosis and activation of nuclear
Manual laborer 15 16.3 factor kappa B. The effects induce the formation of inflam-
Housekeeper 8 8.7 matory enzymes, cytokines, and chemokines.16 One previous
Businessman 4 4.3
Unemployed 46 50
study reported that multiple organ dysfunction is the main
Reason for exposure to poison etiology of death from paraquat intoxication.8 Therefore,
Accidental 3 3.3 paraquat intoxication can reasonably induce SIRS. In our
Intentional 89 96.7 study, we found that body temperature, respiratory rate, white
History of suicide attempts 42 45.7 blood cell count, and heart rate in the ED met the criteria for
Co-ingestion with other drugs 9 9.8
Amount of paraquat ingested (mL) 100.4  73.7
SIRS. The body temperature, respiratory rate and white blood
Period from poison exposure to arrival 4.8  8.7 cell count differed significantly between Group 1 and 2 pa-
at hospital (h) tients (SIRS being more prominent in group 2). Patients with
Clinical features on arrival in the emergency prominent SIRS in the ED were therefore at a higher risk of
department early mortality.
Body temperaturea ( C) 36.1  1.0
Heart ratea (bpm) 92.8  21.5
Initial heart function was another key factor associated with
Respiratory ratea (per min) 22.8  8.6 early mortality. Few previous studies have analyzed the rela-
Mean arterial pressurea (mmHg) 103.7  18.4 tionship between initial heart function and outcomes in patients
White blood cell count (103/mL) 13.1  6.4 with paraquat intoxication. Chang et al reported no significant
Glasgow Coma Scorea 13.8  2.5 association between mean arterial pressure on arrival in the ER
Blood pH 7.4  0.1
Blood PO2 (mmHg) 82.6  20.8
and mortality.9 However; in our study we found that Group 2
Blood PCO2 (mmHg) 31.6  7.4 patients had higher heart rates and mean arterial pressures
Blood HCO3 (mmol/L) 21.0  6.2 during the initial ED stay. We suspect that the heart rate and
Blood creatinine (mg/dL) 1.7  1.3 stroke volume increased to compensate for decreased systemic
Blood Na (meq/dL) 140.0  4.2 vascular resistance due to vessel dilatation secondary to oxi-
Blood K (meq/dL) 3.3  0.6
Apache II score 13.1  9.4
dative stress from the inflammatory enzymes, cytokines and
Blood paraquat level (mg/mL) 19.6  61.9 chemokines.16 After several hours, damaged myocardial cells
Patient data during hospitalization can no longer compensate for the lower vascular resistance,
Urine output in the first 24 h (mL) 2510.3  2120.6 even with an increased heart rate and output meaning that
Period from poison exposure to O2 41.3  43.7 cardiovascular collapse might be unavoidable. Two previous
desaturation (h)
Acute lung injury
studies mentioned that early mortality from paraquat intox-
Yes 35 40.7 ication might be due to cardiogenic shock, but provided no
No 51 59.3 evidence to support this theory.2,4 Higher initial heart rates
Survival time over 72 h 58 63.0 indicated a high risk of poor outcome in this study.
Hospital mortality 62 67.4 Initial kidney function was another key factor associated
bpm beats per minute. with outcome. Lee et al reported that a lower degree of renal
a
Measured by emergency department triage. failure on admission is a good prognostic factor of survival.17
and a lower potassium level were the most important factors Moreover, one previous study reported that hypokalemia in
predicting longer survival (Table 3). Patients with a history of patients with paraquat intoxication, possibly caused by a direct
suicide attempts and higher blood paraquat level were not oxidative injury to mechanisms of potassium reabsorption in
significantly associated with survival over 72 hours. the renal tubules, was also a prognosticator of poor outcome.9
In our study, we found the levels of creatinine and potassium,
3.4. Initial heart rates of patients who survived for which are associated with renal function, were the most
longer than 72 hours important factors predicting survival over 72 hours. A high
level of creatinine and low level of potassium indicated early
Hyper-hemodynamics in the acute stage was associated mortality. Significantly lower urine output in the first 24 hours
with a poor outcome. The heart rates during the first 12 hours was also noted in patients with early mortality. Acute kidney
after arriving in the ED were significantly higher in Group 2 injury occurred in more than half of patients with paraquat
than Group 1 (2e12 hours, all p < 0.05; Fig. 1). intoxication in one previous study.18 The extent of renal
 H.-L. Liu et al. / Journal of Acute Medicine 3 (2013) 6e10 9

Table 2
Factors associated with survival for longer than 72 hours among patients with paraquat intoxication.
Survival over 72 h p
Yes (n 58) No (n 34)
No. % No. %
Sex
Male 39 67.2 29 85.3 0.084
Female 19 32.8 5 14.7
Age (mean  SD, y) 41.8  16.3 58.1  15.5 <0.001
Occupation
Farmer 8 13.8 11 32.4 0.131
Worker 11 19.0 4 11.8
Housekeeper 6 10.3 2 5.9
Businessman 4 6.9 0 0.0
Unemployed 29 50.0 17 50.0
Reason for exposure to poison
Accidental 3 5.2 0 0.0 0.293
Intentional 55 94.8 34 100.0
History of suicide attempts
Yes 21 36.2 21 61.8 0.029
No 37 63.8 13 38.2
Co-ingestion with other drugs
Yes 6 10.3 3 8.8 1.000
No 52 89.7 31 91.2
Period from poison exposure to arrival at hospital (h) 5.5  10.7 3.5  3.3 0.236
Laboratory data from the emergency department
Blood paraquat level (mg/mL) 1.5  3.4 54.0  97.4 <0.001
White blood cell counta (103/mL) 11.5  5.1 15.8  7.4 <0.001
Blood pH 7.441  0.1 7.379  0.1 0.002
Blood PO2 (mmHg) 80.6  19.8 85.6  22.3 0.264
Blood PCO2 (mmHg) 33.6  5.7 28.6  8.6 <0.001
Blood HCO3 (mmol/L) 23.2  4.5 17.7  7.0 <0.001
Blood creatinine (mg/dL) 1.4  1.4 2.2  1.0 <0.001
Blood Na (meq/dL) 139.9  3.7 140.1  4.9 <0.001
Blood K (meq/dL) 3.4  0.5 3.0  0.7 <0.001
Period from poison exposure to O2-desaturation (h) 67.5  46.9 13.4  10.1 <0.001
Apache II score 13.0  8.6 13.2  10.8 0.769
Body temperature ( C)a,b 36.4  0.9 35.7  1.0 <0.001
Respiratory rate (per min)a,b 20.7  4.4 26.3  12.2 0.003
Heart rate (bpm)a,b 89.9  18.4 97.8  25.6 0.228
Volume of urine in first 24 h (mL) 2942.2  1996.6 1661.4  2133.6 <0.001
Glasgow Coma Scoreb 14.3  2.2 12.9  2.9 0.002
Mean arterial pressure (mmHg) 100.3  16.1 109.5  20.8 0.022
Acute lung injury
Yes 22 40.0 13 41.9 1.000
No 33 60.0 18 58.1
bpm beats per minute.
a
These variables are included in systemic inflammatory response syndrome criteria.
b
Measured by emergency department triage.

function impairment and hypokalemia in paraquat intoxication
are strongly associated with early mortality. Therefore, for
emergency physicians, we recommend that aggressive treat-
ments might be helpful for salvageable patients (who initially
present with the signs of survival for longer than 72 hours).
However, for patients with a very low chance of survival,
palliative and supportive care might protect their dignity
without increasing unnecessary suffering.
4.1. Limitations
There were some limitations in this study. First, its retro-
spective nature is a limitation. There are two common
commercial preparations of parquet in Taiwan, 24% and 42%
solutions. For a better estimate of ingested dose, using the
weight (g; g/kg of body weight is best) rather than volume of
consumption. In this study, however, we cannot confirm the
actual concentration or weight for the quantity ingested (too
much missing data). Second, self-reporting of the time and
amount of paraquat ingested may have been affected by
underreporting and may not be accurate. Third, lack of uni-
formity in treatment because of changes in understanding
about paraquat intoxication over the years of this study may
have influenced the outcome for individual patients. Unfor-
tunately, the overall survival rate was still low. All patients
received aggressive treatment in the ED, but most of them died
10 H.-L. Liu et al. / Journal of Acute Medicine 3 (2013) 6e10

Table 3 study. The presence of SIRS, early tachycardia and renal

Logistic regression analysis. failure predicted early mortality.
Odds ratio p
(95% confidence interval)
Agea 0.92 (0.88e0.96) 0.001 Conflicts of interest
Sex
Male 1 0.864
Female 1.25 (0.08e17.33)
There were no conflicts of interest related to this study.
History of suicide attempts
Yes 2.13 (0.12e65.44) 0.752
No 1 Acknowledgments
Blood paraquat level 1.57 (0.95e2.88) 0.115
White blood cell count 1.25 (0.72e1.23) 0.643
We thank Changhua Christian Hospital for financially
Blood pH 2.74 (0.13e2.42) 0.521
Blood PCO2 1.51 (0.75e3.15) 0.353 supporting this research.
Blood HCO3 0.69 (0.12e1.42) 0.136
Blood creatininea 0.62 (0.37e0.90) 0.004
Blood Na 1.02 (0.68e1.78) 0.821 References
Blood Ka 10.53 (2.25e44.32) 0.001
Period from poison exposure to 1.25 (0.67e2.62) 0.431
1. Sagar GR. Use and usefulness of paraquat. Hum Toxicol. 1987;6:7e11.
O2-desaturation
2. Lock EA, Wilks MF. Paraquat. Handbook of Pesticide Toxicology. 2nd ed.
Body temperature 0.88 (0.15e4.96) 0.453
San Diego: Academic press; 2001.
Respiratory rate 1.13 (0.98e1.56) 0.257
3. Proudfoot AT, Swewart MS, Levitt T, Widdop B. Paraquat poisoning:
Volume of urine in first 24 h 1.21 (0.98e1.24) 0.251
significance of plasma-paraquat concentrations. Lancet. 1979;2:
Glasgow Coma Score 1.54 (0.97e2.23) 0.077
330e332.
Mean arterial pressure 2.35 (0.88e2.27) 0.063
4. Vale JA, Meredith TJ, Buckley BM. Paraquat poisoning: clinical features
a
Significant factors. and immediate general management. Hum Toxicol. 1987;6:41e47.
5. Bismuth C, Garnier R, Dally S, Fournier PE, Scherrmann JM. Prognosis
during their hospital stay. However, patients who survived for and treatment of paraquat poisoning: a review of 28 cases. J Toxicol Clin
longer than 72 hours after primary ED care have a better Toxicol. 1982;19:461e474.
6. Suntres Zacharias E. Role of antioxidants in paraquat toxicity. Toxicology.
chance of receiving further treatment or critical care treatment
2002;180:65e77.
in the intensive care unit. Identifying the factors associated 7. Mascie-Taylor BH, Thompson J, Davidson AM. Haemoperfusion inef-
with early mortality may offer primary clinicians information fective for paraquat removal in life threatening poisoning. Lancet.
on which to make correct evaluations and decisions and 1983;2:1376e1377.
increase the chances of survival. We hope that this topic will 8. Afzali S, Gholyaf M. The effectiveness of combined treatment with
methylprednisolone and cyclophosphamide in oral paraquat poisoning.
be analyzed in a prospective study in the future.
Arch Iranian Med. 2008;11:387e391.
9. Chang MW, Chang SS, Lee CC, Sheu BF, Young YR. Hypokalemia and
5. Conclusions hypothermia are associated with 30-day mortality in patients with acute
paraquat poisoning. Am J Med Sci. 2008;335:451e456.
The patient characteristics and predictors of early mortality 10. Senarathna L, Eddleston M, Wilks MF, et al. Prediction of outcome after
paraquat poisoning by measurement of the plasma paraquat concentration.
in patients with paraquat intoxication were presented in this QJM. 2009;102:251e259.
11. Eddleston M, Wilks M, Buckley N. Prospects for treatment of
paraquat-induced lung fibrosis with immunosuppressive drugs and the
need for better prediction of outcome: a systemic review. QJM. 2003;96:
809e824.
12. Agarwal R, Srinivas R, Aggarwal AN, Gupta D. Immunosuppressive
therapy in lung injury due to paraquat poisoning: a meta-analysis. Sin-
gapore Med J. 2007;48:1000e1005.
13. Savy FP, Duval G, Her B, Canu P, Fintelz P. Failure of chemotherapy and
radiotherapy in pulmonary fibrosis caused by paraquat. Ann Fr Anesth
Reanim. 1988;7:159e161 [in French].
14. Bateman DN. Pharmacological treatments of paraquat poisoning. Hum
Toxicol. 1987;6:57e62.
15. Hampson EC, Pond SM. Failure of haemoperfusion and haemo-
dialysis to prevent death in paraquat poisoning. A retrospective re-
view of 42 patients. Med Toxicol Adverse Drug Exp. 1988;3:
64e71.
16. Gawarammana IB, Buckley NA. Medical management of paraquat
ingestion. Br J Clin Pharmacol. 2011;72:745e757.
17. Lee EY, Hwang KY, Yang JO, Hong SY. Predictors of survival after acute
paraquat poisoning. Toxicol Ind Health. 2002;18:201e206.
Fig. 1. The heart rates during the first 12 hours after arriving in the emergency 18. Kim SJ, Gil HW, Yang JO, Lee EY, Hong SY. The clinical features of
department (ED) were significantly higher in patients who did not survive over acute kidney injury in patients with acute paraquat intoxication. Nephrol
72 hours (2e12 hours, all p < 0.05). Dial Transplant. 2009;24:1232e1237.