Forensic Science International, 49 (1991) 215-224 Elsevier Scientific Publishers Ireland Ltd.

A FATAL CASE OF PARENTERAL

P. FERNANDEZa, A. OTEROC

215

PARAQUAT POISONING

A.M. BERMEJOa, M. LOPEZ-RIVADULLAa,

A. CRUZa, E. RODRIGUEZb and

uDepartnwnt of Legal Medicine, Service of Forensic Toxicology, Faculty of Medicine, University of Santiago de Compostela, and bIntensive Care Unit and “NephrologyService, Hospital Ntra. Sra. de1 Cristal, Ore-me (Spain) (Received February 2&t, 1990) (Revision received August 2nd, 1990) (Accepted January 3Oth, 1991)

Summary The chief clinical and analytical aspects of the suicide of a 21-year-old male with psychiatric problems by parenteral administration of a 200 g/l aqueous solution of paraquat are described. Paraquat levels were determined in plasma, urine, kidney, liver and lung after autopsy. Tissue damage was studied by electron microscopy. The death ensued from pulmonary dysfunction 15 days after hospital admission. Key words: Poisoning;

Paraquat;

Parenteral

administration;

Suicide

Introduction Paraquat, 1,l ‘-dimethyl-4,4’-bipyridylium cation, is an effective contact herbicide that is highly toxic to man and animals. In recent years, there have been many cases of poisoning by ingestion [l-4] and parenteral injection [5-71 of paraquat. In patients who survive 5 days or longer but eventually die from paraquat poisoning, the most characteristic features are damage to the lung and kidney [ES],with the cause of death usually attributed to anoxia as a consequence of extensive lung damage. In this paper, a fatal case of paraquat intoxication, including clinical, analytical and morphopathological features is described. Case

report

The patient, a 21-year-old male with a history of psychiatric problems, was admitted to the intensive care unit with nausea, vomiting and abdominal pain 12 h after parenteral self-administration of about 4 ml of Gramoxone, which is 20% paraquat. Though administration was basically intravenous, the presence of necrotic tissue in the proximity of the injection site suggests that a portion of the injected solution may have escaped from the vein. 0379-0733i91/$03.50 0 1991 Elsevier Scientific Publishers Printed and Published in Ireland

Ireland Ltd.

216

The man was treated, including haemoperfusion and administration of propranolol, but death occurred 15 days after hospital admission, as the result of pulmonary failure. Clinical analyses and radiography

Biochemical parameters Table 1 lists the values of biochemical parameters determined between the patient’s admission and death. The most striking feature is the rise in blood creatinine and urea levels reflecting kidney damage. Bilirubin and transaminase concentrations also rose considerably as the result of liver damage, as did glucose and alkaline phosphatase levels. Platelet levels fell as a result of the haemoperfusion treatment, only to rise again later. The leucocytosis observed during the last few days was due to pneumonia (probably of bacterial origin).

Gasometric parameters The most critical of the patient’s gasometric parameters (Table 2) was PO,, which was initially lower than in oral paraquat poisoning cases and fell progressively until day 11. Though oxygen enhances the toxicity of paraquat [9], this made it necessary to administer oxygen, first at a rate of 3 ml/min and later, on day

TABLE

1

EVOLUTION

OF BIOCHEMICAL

PARAMETERS

Day

1

2

3

5

7

Glucose (mmohl)

7.7

6.3

8.7

7.6

Urea (mmolll) Creatinine

6.9

18.6

25.3

28.9

667

683

532

106184

103177

(PmoW Total/direct bilirubin (pmol/l) CPK (U/l) GOT (U/l) GPT (U/l) LDH (U/l) Platelets

(low

Prothrombin Leucocytes

(109)

(%)

14

15

5.9

9.9

16.7

17.2

33.6

41.2

34.3

28.1

627

780

92177

489 43

80

116

29

152

259 544

336

107

70 12

11

129

259

53

61

Hct (o/o)

40

42

Hb (mmolfl) Alkaline phosphatase

8.06

8.68

(ufl)

11

160/96

8

58

44 9.30

544 61

41 8.68

61 39

48 29

37 7.44

35 6.82

129

23 30 5.99

217

TABLE

2

EVOLUTION

Day

Pco, (mmHg) PH BE (mmolll) HCO, (mmol/l) so, (%) FIO, (I/min) PEEP

OF GASOMETRIC

PARAMETERS

1

3

4

5

6

7

9

11

18

15

69

50

40

39

41

46

42

38

45

37

32

26

25

30

24

28

29

24

38

41

7.46 1.2

7.44 -3.6

7.51 -0.3

7.43 -1.7

7.48 -2.5

7.45 -2.6

7.47 -2.2

7.43 -5.1

7.31 -5.8

7.25 -8.1

23.3

18.0

19.8

20.3

18.1

18.9

20.7

16.1

19.4

18.6

95

88

a2

79

85

90

83

74

78

64

air

air

air

air

air

air

(llmin)

Fig. 1. X-ray of thorax on the day of hospital admission.

3.0

0.6

0.4

5

5

218

13, by mechanical ventilation using PEEP to reduce oxygen pressure in exhaled breath. In spite of these measures, irreversible lung lesions led to the patient’s death. Radiography Figures 1 and 2 show thoracic X-rays taken on days 1 and 10. Whereas the first reflects no significant alterations of the lungs, the terminal stage shown in the second involves the presence of large areas of fibrosis and pulmonary oedema [lO,ll] in the lung parenchyma. Paraquat levels Paraquat was separated from biological media by elution from Dowex AW50 ion exchange resin using a strongly acid eluent. To a 3 ml sample of the eluate was added 0.4 ml of a 2% solution of sodium dithionite in 1N NaOH, and after gentle stirring the absorbance of the blue reaction product at 396 nm was measured in a Perkin-Elmer Model 552 double-beam spectrophotometer [12]. Table 3 lists the concentrations of paraquat in plasma before and after haemoperfusion treatment. Table 4 lists the post-mortem levels of paraquat in plasma, urine, liver, kidney and lung.

Fig. 2. X-ray of thorax on day 10 after hospital admission, showing areas of fibrosis and pulmonary

219 TABLE

3

HAEMOPERFUSION

IN PARENTERAL

Time

PARAQUAT

POISONING (12 mg/kg)

Plasma paraquat concentrations (wglml)

(hour no.)

Pre-HP

Post-HP

H 12 H 16

0.62 0.83

0.19 0.17

H 20

0.28

0.15

Morphopathology Macroscopic appearance Figure 3 shows the patient’s lungs, which are greatly enlarged and totally hepatized, with subpleural haemorrhages. As is usual in paraquat poisoning cases, the lungs were of a “meaty” consistency. The kidneys (Fig. 4) exhibited oedematosis and large necrotic areas. The liver (Fig. 5) was of average consistency and its smooth surface exhibited alternate areas of necrosis and haemorrhage. Electron microscopy Electron microscopy of lung tissue reflected progressive deterioration of the lung parenchyma leading to a diffuse alveolar lesion whose chief characteristics are illustrated in Figs. 6-8. Figure 6 shows intravascular coagulation by deposition of fibrin between the endothelium and an erythrocyte; such coagulation would impede the diffusion of oxygen and hence give rise to the hypoxaemia observed. Fig. ‘7shows evident division of the basal membrane. Fig. 8 shows the final state of the lung parenchyma, with total structural disorganization, large deposits of collagen mingling with cellular remains (lymphocytes and macrophages), and large amounts of plasma proteins.

TABLE

4

POST-MORTEM

PARAQUAT

CONCENTRATIONS

IN BODY FLUIDS AND ORGANS

Samples

Paraqat concentration (PgJml or pgfg)

Plasma Urine

0.10 16.50 4.36 8.61 6.24

Liver Kidney Lung

220

Fig. 3. Enlarged,

totally hepatized lungs with subpleural haemorrhage.

Fig. 4. Oedematose

kidneys with large necrotic areas.

221

Fig. 5. Smooth-skinned

liver with alternating

areas of necrosis and haemc

Fig. 6. Electron micrograph of lung tissue, showing intravascular between the endothelium and an erythrocyte ( x 60,000).

coagulation by deposition of fibrin

Fig. ‘7. Electron

micrograph

of lung tissue, showing division of the has;al membrane (x 10,O100).

Fig. 8. Electron micrograph of lung tissue, showing total disorganization of lung parenchyma, large deposits of collagen mingling with cell debris and plasma proteins (x 4000).

with

223

Discussion Pulmonary degeneration was faster in the case described here than in oral paraquat poisoning, though the medium-term clinical evolution was totally similar to that of oral cases. The salient analytical feature is the progressive fall in arterial oxygen pressure (Table 2), that is, hypoxaemia brought about by the paraquatinduced respiratory distress [13]. It is possible that the patient survived longer than in other cases, primarily because a smaller dosage of paraquat had been taken (about 12 mg/kg), though the late administration of oxygen may also have played some role. The first plasma paraquat level determined, 0.62 fig/ml, was nevertheless within the lethal range indicated by Proudfoot’s curve [14]. The rise in the concentration of paraquat in plasma (sample 2 of Table 3) may perhaps be due either to release from tissue following elimination in urine, or to its being displaced from its cell-binding sites as the result of propanolol treatment. The paraquat concentrations observed in liver, kidney and lung agree with the results obtained by other authors [15,16] with the accumulation in kidney that led to renal failure being greater than the level reached in lung, the most affected organ. It may be noted that the haemoperfusion treatment was quite ineffective [17], all that it achieved being a reduction in plasma paraquat levels that, due to its large volume of distribution, had just a minor impact on the total quantity of paraquat present in the body. In conclusion, the above findings illustrate the fact that the penetration of even small quantities of paraquat in the human body rapidly causes irreversible damage (lung damage especially) regardless of its route of entry. Acknowledgments The authors wish to thank Rosario Parga-Castro tance in the analytical determinations.

for her dedicated technical assis-

References 1 2 3

4 5 6

M.D. Osselton, M.D. Hammond and A.C. Moffat, Statistics for deaths from poisoning 1973 to 1975 for England and Wales. J. Forensic Sci. Sot., 20 (1980) 125-134. J.M. Scherrman, M. Galliot, R. Garnier and C. Bismuth, Intoxication a&u& par Ie Paraquat: inter& pronostique et therapeutique du dosage sanguin. Toxicol. Eur. Res., 5 (1983) 141-145. J.H. Frelon, P. Merigot, R. Garnier, C. Bismuth and M.L. Efthymiou, Prognostic factors of acute Paraquat poisoning. Retrospective study of the cases collected in 1981 at the Poison Control Center of Paris. Toxicol. Eur. Res., 5 (1983) 163-169. R. Azebedo-Bernarda and D.N. Vieira, Intoxicacao mortal por Paraquat. J. Sot. Cienc. Med. Lisboa, 72 (1988) 41-46. C.H. Almog and E. Tal, Death from Paraquat after subcutaneous injection. Br. Med. J., 3 (1967) 721. J.B. Harley, S. Grinspain and R.K. Root, Paraquat suicide in a young woman: results of therapy directed against the super-oxide radical. Yak J. Biol. Med., 50 (1977) 481-488.

224 ‘7 M.S. Hendy, P.S. Williams and P. A&ill, Recovery from severe pulmonary damage due to Paraquat administered intravenously and orally. Thorax, 39 (1984) 874-875. 8 R.D. Fairshter, S.M. Rosen, W.R. Smith, F.L. Glauser, D.M. Mcrae and A.F. Wilson, Paraquat poisoning: new aspects of therapy. Q. J. Med., 45 (1976) 551-565. 9 M.L. Rhodes, D.C. ZabaIa and D. Brown, Hypoxic protection in Paraquat poisoning. Lab. Znvest., 5 (1976) 496-500. 10 G.M. Copland, A. Kolin and H.S. Shulman, Fatal pulmonary intra-alveolar fibrosis after Paraquat ingestion. New Engl. J. Med., 291 (1974) 290-292. 11 A.J.S. Gardiner, Pulmonary oedema in Paraquat poisoning. Thorox, 27 (1972) 132. 12 J. Knepil, A short, simple method for the determination of Paraquat in plasma. Clin. Chim. Acta, 79 (1977) 387-390. 13 J.A. Vale, T.J. Meredith and B.M. Buckley, Paraquat poisoning: clinical features and immediate general management. Hum. Toticol., 6 (1987) 41-47. 14 A.T. Proudfoot, M.S. Stewart, J. Lewitt and B. Widdop, Paraquat poisoning: significance of plasma-Paraquat concentrations. Lancet, 2 (1979) 330-332. 15 MS. Rose, E.A. Lock, L.L. Smith and I. Wyatt, Paraquat accumulation: tissue and species specificity. Biochem. Pharmacol., 25 (1976) 419-423. 16 L.A. Russell, Paraquat poisoning: toxicologic and pathologic findings in three fatal cases. Clin. Toxicol., 18 (1981) 915-928. 17 F.L. Van de Vyver, J. Van de Sande, G.A. Verpooten, M.E. de Broe, M. Van den Heede and A. Heyndrickx, Haemoperfusion ineffective for Paraquat removal in life-threatening poisoning. Lancet, 2 (1983) 173.

A fatal case of parenteral paraquat poisoning.

The chief clinical and analytical aspects of the suicide of a 21-year-old male with psychiatric problems by parenteral administration of a 200 g/l aqu...
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