Arch. Toxicol. 33, 141--149 (t975) 9 by Springer-Verlag 1975
A Comparison of Two Types of Acute Carbon Monoxide Poisoning Maciej Bogusz, L e o n Cholewa, J a n u s z P a c h a n d K s e n i a Mtodkowska Institute of Forensic Research, Krak6w, Poland, and the Toxicological Clinic, Academy of 1Vfedicinein Krak6w, Poland Received July 5, 1974
Abstract. I n 47 patients treated at the Toxicological Clinic in KrakSw for coalstove-gas poisoning, the aspartate aminotransferase, lactate dehydrogenase, LDH 1 isoenzyme activities, and the lactate level were studied. Findings were compared with those of earlier investigations carried ou~ on a group of patients poisoned by lighting gas; qualitatively changes in both groups were similar. The biochemical parameters studied aided in quantitative evaluation of the patients' condition: a threefold increase in lactate Ievel on admission to the hospital and a likewise threefold increase in aspartate aminotransferase activity after 24 hrs of treatment are indications of severe poisoning. Key words: Coal-Steve Gas Poisoning -- Lighting-Gas Poisoning -- Biochemical Changes.
Zusammen/assung. Zum Vergleich yon 2 Formen der almten KoMenmonoxydvergiftung bei 47 Patienten, die in der Toxikologischen Klinik in Krak6w wegen einer Rauchgasvergiftung behandelt warden, wurde die Aktivit~t der AspartatAminotransferase, der Laetat-Dehydrogenase, des LDHl-Isoenzyms und der Lactatkonzentration untersucht. Die Ergebnisse wurden mit Befunden yon frfiheren Untersuchungen an Kranken mit akuten Leuchtgasvergiftungen verglichen, wobei sich eine qualitative ~bereinstimmung der Ergebnisse ergab. Die Fermentaktivit~ten k6nnen bei der Einsch~tzung der Schwere niitzlich sein. Eine 3fache Steigerung der Lactatkonzentration im Blur bei der Aufnahme ist ebenso wie eine 3fache ErhShung der Aktivit~t der Aspartat-Aminotransferase nach 24 Std als Hinweis fiir eine schwere Intoxikation zu verwerten. Schli~selw~rter: Rauehgasvergiftung -- Leuehtgasvorgiftung -- Bioehemische Ver~nderungen. Some i 2 0 cases of c a r b o n m o n o x i d e poisoning are hospitalized a n n u a l l y a t t h e Toxicological Clinic i n K r a k 6 w , out of which a b o u t 75% are caused b y lighting gas, a b o u t 20% are poisonings b y coal-stove gas, i.e. gas from b a d l y f u n c t i o n i n g coal stoves a n d k i t c h e n coal ranges, a n d t h e r e m a i n i n g 5 % c o n s t i t u t e those caused b y c o m b u s t i o n a n d i n d u s t r i a l gases.
142
M. Bogusz et al.
Accidental poisonings b y lighting gas usually occur in the bath or during housework; in suicidal poisonings gas is inspired within closed rooms. Both in accidental and suicidal poisonings patients are exposed to a high concentration of carbon monoxide; they rapidly lose consciousness and die shortly thereafter; some are hospitalized after a comparatively brief exposure (the mean time of exposure in our study was i hr and 20 min, average COHb saturation on admission to the Clinic reached 35%). On the other hand, coal-stove gas poisonings nearly always occur at night, during sleep. These poisonings, always accidental, are characterized by a long exposure time to comparatively low CO concentrations (the mean time of exposure was 5 hrs and 30 rain, and the average COHb saturation was t7%). On admission to the Clinic the poisoned patients are often conscious. This fact, in addition to a low COHb value, m a y lead to erroneous evaluation of the patient's condition. The studies carried out by one of our co-authors (Path, 1974) have also shown a more frequent occurrence of complications following coal-stove-gas poisonings. As is known, COHb value on admission to the hospital does not constitute an indicator for the assessment of severity of poisoning (Bogusz et al., 1972; Burmeister and Neuhaus, t970). The German authors, Burmeister and Neuhaus (1970), based the evaluation of the severity of poisoning on the state of acid-base balance and on the activities of the circulatory and respiratory systems, whereas our studies were aimed at observing some biochemical changes occurring during hypoxia of the tissues. I t was shown that the levels of lactate (LA) and pyruvate (PA) increased in poisoning by lighting gas, becoming most distinct at the time of admission, and the activities of aspartate aminotransferase (AspAt) and lactate dehydrogenase (LDH) were increased, reaching their maximum after 24 hrs of treatment (Bogusz et al., t972). I n considering the conflicts between studies on lighting-gas poisoning and coal-stove-gas poisoning, dealt with at the beginning of this paper, we are led to confirm the conclusions resulting from the previous studies on patients poisoned by coal-stove gas.
Material and Methods We studied a group of 47 patients (28 females and 19 males) between the ages of 14 and 88 who were treated at the Toxicological Clinic from 1971 to 1972 for coalstove gas poisoning. The time of exposure to gas varied between I and 16 hrs, and the time elapsing from the cessation of exposure until admission to the Clinic ranged from 1 to 5 hrs. LA concentration in the blood of poisoned patients and the activities of AspAt, LDH, and LDH1 in serum were determined. These tests were performed on admission to the hospital and again after 24 hrs of treatment. LA determination reagent
Two Types of Carbon Monoxide Poisoning
143
Table 1. Objective evaluation of patient condition on the base of neurological syndromes Degree
Specification of Syndromes
I Good
No disturbances of consciousness; possible of muscular twitchings;
II Medium
and tonic or clonic convulsions. Disturbances of consciousness; and possible simultaneous excessively intensified tendon reflexes, Babiuski reflex, tonic or elonic convulsions, and intensified muscular tonus.
III G~ave
Total loss of consciousness without other neurological symptoms.
IV Very grave
Complete loss of consciousness with simultaneous excessively intensified tendon reflexes, Babinski reflex, tonic convulsions, clonic conVulsions, intensified muscular tonus, partial or total elimination of tendon reflexes, pupillary, corneal, and swallowing reflexes with a diffusely diminished muscular tonus.
kits were supplied by Boehringer, and AspAt and L D H determination kits were supplied by Fermognost. LDH 1 activity was determined according to Wroblewski et al. (1961). This method is simple and the results are just as reliable as those obtained by eleetrophoretic methods (Auvinen and Konttinen, 197~). As in the preceding paper, the control group consisted of 50 healthy adults (Table 2). The patients were divided into sub-groups with regard to sex, age, time of exposure to coal-stove gas, clinical symptoms, and changes in ECG curve. For evaluation of the patients' condition at the initial stage, the classification used at the Clinic was based on the appearance of definite neurological syndromes (Path, 1974) (Table 1). Changes in the range of ECG curve (in the range of ST section, in that ofT, P deflection, and of the QRS complex as welt as disturbances in the conductivity and rhythm) were regarded as pathological characteristics which were not revealed initially but appeared during hospitalization at the Clinic, or when the changes with previous documentary evidence were exacerbated. Coal-stove gas poisonings often concern more than one person. In our patients 8 pairs had been poisoned simultaneously. I t provided the opportunity to observe some biochemical disturbances which arose in very similar conditions. Results and Discussion N o differences in t h e s t u d i e d p a r a m e t e r s was f o u n d b e t w e e n t h e p a t i e n t s d i v i d e d i n t o g r o u p s according t o t h e i r sex (Table 2). W h e n t h e p o i s o n e d p a t i e n t s were d i v i d e d into t w o age g r o u p s (up t o 40 a n d a b o v e 40 y e a r s of age) significantly h i g h e r A s p A t - 2 4 v a l u e s were o b s e r v e d in e l d e r l y p a t i e n t s (Table 3). W h e n e x p o s u r e t i m e was l e n g t h e n e d , a d i s t i n c t increase in e n z y m a t i c changes was n o t e d (Table 4). B y d i v i d i n g t h e g r o u p of p a t i e n t s w i t h r e s p e c t t o clinical picture, a g r a d u a l increase in L A level a n d e n z y m e a c t i v i t y was o b s e r v e d (Table 5). T h e a c t i v i t y of A s p A t deserves special a t t e n t i o n : I n t h e g r o u p of p a t i e n t s w i t h o u t
144
M. Bognsz eta/.
Table 2. The results of investigations in the subgroups divided according to the sex Sex
female (28)
LA 0 ~ s
male (19) controls (50)
.~ s ~ s
24.0 12.6 24.7 tl.9 10.0 2.1
24 16.9 12.7 19.3 tt.4
AspAT 0 24
LDH 0
21.5 7.8 22.5 12.7 6.1 2.7
118 54 126 46 77 29
30.6 17.9 30.9 24.8
24 133 62 149 62
LDH~ 0 24 55 20 67 20 23 10
65 36 69 30
Table 3. The results of investigations in the subgroups divided according to the age of patients Age
up to 40 years (25) ~ s over 40 years ~ (22) s
LA 0
24
AspAT 0 24
LDH 0
24
2i.1 10.4 27.9 i5.1
16.9 7.5 i9.0 8.4
19.4 il.7 24.8 8.0
118 52 125 37
t29 63 152 41
26.4 16.7 35.7 i0.5
LDH 1 0 24 55 16 66 3i
62 29 72 32
P < 0.05
clinical s y m p t o m s or E C G changes, t h e m e a n a c t i v i t y of t h i s e n z y m e a t t h e 2 4 t h h r of o b s e r v a t i o n was twice as high as t h e u p p e r l i m i t of t h e n o r m a l range. The a c t i v i t y of this e n z y m e in t h e group w i t h 2 n d a n d 3rd degree poisoning was higher t h a n in t h e p a t i e n t s in t h e g r a v e s t condition. This is p r o b a b l y caused b y g r e a t e r m o t o r a c t i v i t y in t h e p a t i e n t s w i t h less severe poisoning a n d b y a s u b s e q u e n t release of t h e e n z y m e of m u s c u l a r origin i n t o t h e serum. I n p a t i e n t s w i t h p a t h o l o g i c a l E C G tracings, biochemical changes showed significantly higher values (Table 6). T h e activities of t h e e n z y m e s u n d e r e x a m i n a t i o n d i d n o t d e p e n d on C O H b c o n c e n t r a t i o n , whereas t h e L A level was significantly h i g h e r in t h e p a t i e n t s w i t h higher C O H b s a t u r a t i o n (Table 7). As is k n o w n , t h e C O H b s a t u r a t i o n s t u d i e d on a d m i s s i o n to h o s p i t a l d e p e n d s on t h e t i m e e l a p s e d from t h e cessation of exposure to t h e t i m e blood is collected for t e s t i n g (Bogusz et al., i972). I n our p a t i e n t s t h e t i m e r a n g e d f r o m t t o 5 hrs. T h e L A level, j u s t as t h e C O H b s a t u r a t i o n , reaches its h i g h e s t v a l u e d u r i n g e x p o s u r e to c a r b o n monoxide, a n d after its cessation e x p o n e n t i a l l y drops. A m o r e precise analysis showed t h a t t h e p a t i e n t s w i t h high C O H b a n d L A values h a d been b r o u g h t (within i to 2 hrs) t o t h e Clinic c o m p a r a t i v e l y quickly. This i n t e r d e p e n d e n c e b e t w e e n
~ s
over 8 hrs (12)
~ s
~ s
~ s
~ s
symptoms ~ ECG--(17)
s y m p t o m s z E C G + (12)
s y m p t o m s I I - - I I I ~ (8)
s y m p t o m s I V ~ (10)
Clinical a p p e a r a n c e
~ s
6 to 8 hrs (18)
27.9 14.1
27.5 17.5 19.1 12.0
14.5 13.2
15.0 11.1
40.7 23.3 P < 0.001
P < 0.001
25.6 9.2
17.5 13.8
24
27.9 t3.9
26.3 11.4
10.8 4.9
0
21.2 16.3
AspAT
0
24
LA
84 47
P < 0.001
160 51
126 43
0
LDH
P < 0.001
184 54
134 40
87 50
24
P < 0.01
32.8 13.9
27.7 t0.2
24.7 6.6
20.9 12.4
21.4 10.5
14.4 8.3
13.2 7.6
P < 0.001
30.0 12.9
32.9 14.5
19.6 11.2
14.3 6.6
0
17.4 6.2
AspAT
LA
0
24
-P < 0.05
33.6 14.4
50.6 19.2
27.1 13.4
22.3 12.9
24
t33 59
138 61
120 41
108 32
0
LDH
P < 0.01
163 63
i65 68
142 36
112 30
24
T a b l e 5. R e s u l t s of i n v e s t i g a t i o n s in t h e s u b g r o u p s divided a c c o r d i n g to clinical p i c t u r e
~ s
u p to 6 hrs (17)
T i m e o f exposition
79 26
80 31
45 26
24
52 30
42 19
53 24
112 30
84 31
41 22
49 31
24
P < 0.001 P < 0.001
101 41
0
LDH 1
P < 0.05 P < 0.01
70 31
69 30
45 26
0
LDH~
Table 4. T h e r e s u l t s of i n v e s t i g a t i o n s in t h e s u b g r o u p s divided according to t h e l e n g t h of e x p o s u r e
oq
~.
o
P < 0.01
P < 0.01
P < 0.01
26.2 t2.8
20.6 9.6
12.3
7.6
6.2
28.2
14.3
13.2
s
6.6
s
AspAT 0
24
~
17.4
~
No c h a n g e s (17)
C h a n g e s p r e s e n t (30)
LA 0
C h a n g e s in E C G curve
P < 0.01
35.5 17.0
12.9
22.3
24
129 58
3t
108
LDH 0
P < 0.01
155 57
29
t12
24
Table 6. T h e relationship b e t w e e n biochemical a n d electrocardiographical c h a n g e s
64 32
24
53
LDH1 0
P < 0.02
76 38
31
49
24
7~
Two Types of Carbon Monoxide Poisoning
t47
Table 7. The relationship between biochemical changes and COHb saturation COHb saturation up to t5% (30) above 15% (t7)
LA ~ s :~ s
AspAT
LDH
0
24
0
24
0
20.8 I0.8 30.5 13.3
t6.6 8.4 20.1 7.2
22.1 14.6 21.6 8.8
29.6 t3.0 32.7 15.7
120 48 t25 30
LDH1 24"
139 48 139 43
b
24
59 24 61 40
64 39 71 37
P < 0.01
the time of patient transport and LA level had not been revealed until the present studies, in which the time of patient transport was sometimes as long as 5 hrs. The biochemical findings in 8 pairs of patients poisoned in shared rooms are presented in the Table 8. This data revealed that even under like exposure to carbon monoxide biochemical changes may differ. Some dependence on age of patient is observed. A comparison of degree of change in our patients and those previously studied who were poisoned by lighting gas shows that the changes produced by coalstove gas are more intense, probably due to a greater length of exposure (Table 9). I n an attempt to evaluate the condition of patients and the clinical course of poisoning, based on the biochemical parameters studied, t i cases were selected from the material under investigation in whom at least two of four criteria were fulfilled: i. LA-O concentration exceeding three times the upper limit of the normal values, 2. AspAt-24 activity exceeding three times the upper limit, 3. LDIt-24 activity exceeding twice the upper limit, 4. LDHx-24 activity exceeding twice the upper limit. Of these I i patients, 9 were in very critical condition on admission (4th degree), and 2 patients were in critical condition (3rd degree). There patients died while treated, and in 4 patients some complications developed during treatment (broncho-pneumonia, psychoorganic syndrome). The time of treatment in this group (excluding cases that ended in death) was t0 to 41 days - - an average of 32 days. Of the remaining 36 patients who did not fulfiill the established criteria, 17 patients did not show any poisoning changes or changes in ECG; in 12 of them only changes in ECG were found; 6 patients were in moderately critical condition (2rid degree); and i patient was in very critical condition (4th degree). This patient (80 years old) developed a complication in the form of pneumonia. I n the remaining patients the treatment ran its course without complicatic as. The period of treatment
M. Bogusz et ul.
148
Table 8. Biochemical changes in 8 pairs of patients, poisoned in shared rooms Sex
Age
Symptoms
ECG
LA-O
AspAT-24LDH-24
LDH1-24
F M F M F M F IV[ F M F M F M F M
77 82 24 29 74 70 22 24 33 32 52 20 48 21 50 18
~ ~ III~ III~ II ~ I~ IV ~ IV ~ ~ ~ II ~ ~ ~ ~ III~ II ~
+ + + + + + + + + + + + --+ +
16.9 16.7 23.2 23.0 27.5 36.6 36.2 31.8 19.9 21.1 36.2 30.7 26.4 18.8 24.8 20.2
12.1 12.0 115.0 82.0 27.2 24.0 79.0 48.6 17.3 21.8 25.6 19.6 24.0 18.0 38.8 26.0
88 48 96 99 49 50 138 103 48 47 47 29 49 37 t31 73
148 106 190 279 100 1t4 288 267 72 133 113 85 77 78 173 151
Table 9. Enzyme activities and lactate level in lighting gas and coal-stove-gas poisoning. The results are expressed in relative values: upper limit of normal values = I LA-O
AspAT-24 LDI-L24
LDH1-24
lighting gas (47) ~ s
t.2 0,8
2.0 1.6
0.8 0,3
0.9 0.5
coal-stove gas (47)
1.7 0.8
2.6 1.7
1,0 0.5
1.3 0.4
~ s
ranged from 4 to 40 days and averaged t0 days. It was significantly s h o r t e r t h a n t h e t i m e of t r e a t m e n t i n t h e p r e c e d i n g g r o u p ( P < 0,001). Summing up the present studies, it can be stated that their results d i d n o t d i f f e r q u a l i t a t i v e l y f r o m t h o s e o b t a i n e d i n t h e g r o u p of p a t i e n t s with lighting-gas poisoning. Regarding enzymatic and ECG changes, similar data for lighting gas were presented by :French authors (Bour et al., 1 9 6 2 ; D u p l a y et al., 1 9 6 7 ; B o u l e t r e a u , 1 9 7 0 ; T h i e l s et al., 1972), a n d A y r e s et al. ( t 9 7 0 ) s h o w e d s i m i l a r c h a n g e s i n l a c t a t e l e v e l i n t h e i r i n v e s t i g a t i o n s . I t s h o u l d b e a d d e d t h a t t h e a l k a l i z a t i o n t r e a t m e n t of t h e p a t i e n t , r e c o m m e n d e d b y B u r m e i s t e r a n d N e u h a u s (1970) w a s also a p p l i e d . I t c o n t r i b u t e d t o a r a p i d c o n t r o l of d i s t u r b a n c e s i n a c i d - b a s e b a l a n c e , w h i c h w e r e r e f l e c t e d i n o u r s t u d i e s b y a h i g h l a c t a t e level.
Two Types of Carbon Monoxide Poisoning
~49
Conclusions 1. B o t h i n lighting-gas poisoning a n d in poisoning b y coal-stove gas, t h e lactate level a n d AspAt, L D H , a n d L D H 1 activities reach the highest values on the 2 n d d a y of t r e a t m e n t . 2. E n z y m a t i c changes increase as time of exposure to coal-stove gas is l e n g t h e n e d ; in addition, these changes are more intense in elderly patients. 3. E n z y m a t i c changes a n d those i n lactate level occur parallel to clinical a n d ECG changes. The A s p A t a c t i v i t y is increased e v e n i n cases in which there are no clinical s y m p t o m s or changes in ECG. 4. A t r i p l e - t h e - n o r m a l lactate level on admission is absolute i n d i c a t i o n for hospitalization. A threefold increase i n A s p A t a c t i v i t y on t h e second d a y of t r e a t m e n t is connected with severe poisoning a n d s t r o n g l y indicates complications.
References Auvinen, S., Konttinen, A. : The diagnostic value of serum LDtt isoenzymes and heat-stable and urea-stable LDH measurements. Acta med. scand. 189, 191 --198 (t971) Ayres, S., Gianelli, S., Mueller, H. : Myocardial and systemic responses to carboxyhemoglobin. Ann. N.Y. Acad. Sci. 174, 268--293 (1970) Bogusz, M., Cholewa, L., Mlodkowska, K., Pach, J. : Biochemical criteria of hypoxia in acute carbon monoxide poisoning. J. Eur. Toxicol. 5, 306--309 (1972) Bouletreau, P. : L'intoxication aigue par l'oxyde de carbone. Paris: Masson 1970 Bour, H., Doroux, P., Glimet, T., Cluvel, H.: Les enzymes du muscle an du coma oxycarbon~e. Sem. HSp. Paris 88, 3152--3156 (1962) Burmeister, H., Neuhaus, G. : Die Behandlung der schweren subakuten Leuchtgasvergiftung beim Menschen. Arch. Toxicol. 26, 277--292 (1970) Duplay, H., Ziegler, G., Gard, A., Pinto, J. : Valeur prognostique des transaminases dans les intoxications par l'oxyde de carbone. Presse m6d. 75, 469--473 (1967) Pach, J. : The prognosis and outline of treatment in acute carbon monoxide poisoning. Folia reed. craeov. (1974) (in press) Thiels, H., Van Dorme, J., Vermeire, P.: Modifications electro-cardiographiques immediates et tardives au cours de l'intoxication oxycarbonne aigue. Lille m4d. 17, t91--198 (1972) Wroblewski, F., Gregory, K. : Lactic dehydrogenase isozymes and their distribution in normal tissues and plasma and in disease states. Ann. N.Y. Acad. Sci. 94, 912--937 (1961) Prof. Dr. Leon Cholewa Dr. med. Maciej Bogusz Dr. med. Janusz Pach Institute of Forensic Research 31033 KrakSw, Westerplatte 9, Poland Toxicological Clinic Institute of Internal Medicine Academy of Medicine, Krak6w, Poland Mgr Ksenia Mtodkowska Department of Clinical Chemistry Institute of Internal Medicine Academy of Medicine, KrakSw, Poland
A Comparison of Two Types of Acute Carbon Monoxide Poisoning Maciej Bogusz, L e o n Cholewa, J a n u s z P a c h a n d K s e n i a Mtodkowska Institute of Forensic Research, Krak6w, Poland, and the Toxicological Clinic, Academy of 1Vfedicinein Krak6w, Poland Received July 5, 1974
Abstract. I n 47 patients treated at the Toxicological Clinic in KrakSw for coalstove-gas poisoning, the aspartate aminotransferase, lactate dehydrogenase, LDH 1 isoenzyme activities, and the lactate level were studied. Findings were compared with those of earlier investigations carried ou~ on a group of patients poisoned by lighting gas; qualitatively changes in both groups were similar. The biochemical parameters studied aided in quantitative evaluation of the patients' condition: a threefold increase in lactate Ievel on admission to the hospital and a likewise threefold increase in aspartate aminotransferase activity after 24 hrs of treatment are indications of severe poisoning. Key words: Coal-Steve Gas Poisoning -- Lighting-Gas Poisoning -- Biochemical Changes.
Zusammen/assung. Zum Vergleich yon 2 Formen der almten KoMenmonoxydvergiftung bei 47 Patienten, die in der Toxikologischen Klinik in Krak6w wegen einer Rauchgasvergiftung behandelt warden, wurde die Aktivit~t der AspartatAminotransferase, der Laetat-Dehydrogenase, des LDHl-Isoenzyms und der Lactatkonzentration untersucht. Die Ergebnisse wurden mit Befunden yon frfiheren Untersuchungen an Kranken mit akuten Leuchtgasvergiftungen verglichen, wobei sich eine qualitative ~bereinstimmung der Ergebnisse ergab. Die Fermentaktivit~ten k6nnen bei der Einsch~tzung der Schwere niitzlich sein. Eine 3fache Steigerung der Lactatkonzentration im Blur bei der Aufnahme ist ebenso wie eine 3fache ErhShung der Aktivit~t der Aspartat-Aminotransferase nach 24 Std als Hinweis fiir eine schwere Intoxikation zu verwerten. Schli~selw~rter: Rauehgasvergiftung -- Leuehtgasvorgiftung -- Bioehemische Ver~nderungen. Some i 2 0 cases of c a r b o n m o n o x i d e poisoning are hospitalized a n n u a l l y a t t h e Toxicological Clinic i n K r a k 6 w , out of which a b o u t 75% are caused b y lighting gas, a b o u t 20% are poisonings b y coal-stove gas, i.e. gas from b a d l y f u n c t i o n i n g coal stoves a n d k i t c h e n coal ranges, a n d t h e r e m a i n i n g 5 % c o n s t i t u t e those caused b y c o m b u s t i o n a n d i n d u s t r i a l gases.
142
M. Bogusz et al.
Accidental poisonings b y lighting gas usually occur in the bath or during housework; in suicidal poisonings gas is inspired within closed rooms. Both in accidental and suicidal poisonings patients are exposed to a high concentration of carbon monoxide; they rapidly lose consciousness and die shortly thereafter; some are hospitalized after a comparatively brief exposure (the mean time of exposure in our study was i hr and 20 min, average COHb saturation on admission to the Clinic reached 35%). On the other hand, coal-stove gas poisonings nearly always occur at night, during sleep. These poisonings, always accidental, are characterized by a long exposure time to comparatively low CO concentrations (the mean time of exposure was 5 hrs and 30 rain, and the average COHb saturation was t7%). On admission to the Clinic the poisoned patients are often conscious. This fact, in addition to a low COHb value, m a y lead to erroneous evaluation of the patient's condition. The studies carried out by one of our co-authors (Path, 1974) have also shown a more frequent occurrence of complications following coal-stove-gas poisonings. As is known, COHb value on admission to the hospital does not constitute an indicator for the assessment of severity of poisoning (Bogusz et al., 1972; Burmeister and Neuhaus, t970). The German authors, Burmeister and Neuhaus (1970), based the evaluation of the severity of poisoning on the state of acid-base balance and on the activities of the circulatory and respiratory systems, whereas our studies were aimed at observing some biochemical changes occurring during hypoxia of the tissues. I t was shown that the levels of lactate (LA) and pyruvate (PA) increased in poisoning by lighting gas, becoming most distinct at the time of admission, and the activities of aspartate aminotransferase (AspAt) and lactate dehydrogenase (LDH) were increased, reaching their maximum after 24 hrs of treatment (Bogusz et al., t972). I n considering the conflicts between studies on lighting-gas poisoning and coal-stove-gas poisoning, dealt with at the beginning of this paper, we are led to confirm the conclusions resulting from the previous studies on patients poisoned by coal-stove gas.
Material and Methods We studied a group of 47 patients (28 females and 19 males) between the ages of 14 and 88 who were treated at the Toxicological Clinic from 1971 to 1972 for coalstove gas poisoning. The time of exposure to gas varied between I and 16 hrs, and the time elapsing from the cessation of exposure until admission to the Clinic ranged from 1 to 5 hrs. LA concentration in the blood of poisoned patients and the activities of AspAt, LDH, and LDH1 in serum were determined. These tests were performed on admission to the hospital and again after 24 hrs of treatment. LA determination reagent
Two Types of Carbon Monoxide Poisoning
143
Table 1. Objective evaluation of patient condition on the base of neurological syndromes Degree
Specification of Syndromes
I Good
No disturbances of consciousness; possible of muscular twitchings;
II Medium
and tonic or clonic convulsions. Disturbances of consciousness; and possible simultaneous excessively intensified tendon reflexes, Babiuski reflex, tonic or elonic convulsions, and intensified muscular tonus.
III G~ave
Total loss of consciousness without other neurological symptoms.
IV Very grave
Complete loss of consciousness with simultaneous excessively intensified tendon reflexes, Babinski reflex, tonic convulsions, clonic conVulsions, intensified muscular tonus, partial or total elimination of tendon reflexes, pupillary, corneal, and swallowing reflexes with a diffusely diminished muscular tonus.
kits were supplied by Boehringer, and AspAt and L D H determination kits were supplied by Fermognost. LDH 1 activity was determined according to Wroblewski et al. (1961). This method is simple and the results are just as reliable as those obtained by eleetrophoretic methods (Auvinen and Konttinen, 197~). As in the preceding paper, the control group consisted of 50 healthy adults (Table 2). The patients were divided into sub-groups with regard to sex, age, time of exposure to coal-stove gas, clinical symptoms, and changes in ECG curve. For evaluation of the patients' condition at the initial stage, the classification used at the Clinic was based on the appearance of definite neurological syndromes (Path, 1974) (Table 1). Changes in the range of ECG curve (in the range of ST section, in that ofT, P deflection, and of the QRS complex as welt as disturbances in the conductivity and rhythm) were regarded as pathological characteristics which were not revealed initially but appeared during hospitalization at the Clinic, or when the changes with previous documentary evidence were exacerbated. Coal-stove gas poisonings often concern more than one person. In our patients 8 pairs had been poisoned simultaneously. I t provided the opportunity to observe some biochemical disturbances which arose in very similar conditions. Results and Discussion N o differences in t h e s t u d i e d p a r a m e t e r s was f o u n d b e t w e e n t h e p a t i e n t s d i v i d e d i n t o g r o u p s according t o t h e i r sex (Table 2). W h e n t h e p o i s o n e d p a t i e n t s were d i v i d e d into t w o age g r o u p s (up t o 40 a n d a b o v e 40 y e a r s of age) significantly h i g h e r A s p A t - 2 4 v a l u e s were o b s e r v e d in e l d e r l y p a t i e n t s (Table 3). W h e n e x p o s u r e t i m e was l e n g t h e n e d , a d i s t i n c t increase in e n z y m a t i c changes was n o t e d (Table 4). B y d i v i d i n g t h e g r o u p of p a t i e n t s w i t h r e s p e c t t o clinical picture, a g r a d u a l increase in L A level a n d e n z y m e a c t i v i t y was o b s e r v e d (Table 5). T h e a c t i v i t y of A s p A t deserves special a t t e n t i o n : I n t h e g r o u p of p a t i e n t s w i t h o u t
144
M. Bognsz eta/.
Table 2. The results of investigations in the subgroups divided according to the sex Sex
female (28)
LA 0 ~ s
male (19) controls (50)
.~ s ~ s
24.0 12.6 24.7 tl.9 10.0 2.1
24 16.9 12.7 19.3 tt.4
AspAT 0 24
LDH 0
21.5 7.8 22.5 12.7 6.1 2.7
118 54 126 46 77 29
30.6 17.9 30.9 24.8
24 133 62 149 62
LDH~ 0 24 55 20 67 20 23 10
65 36 69 30
Table 3. The results of investigations in the subgroups divided according to the age of patients Age
up to 40 years (25) ~ s over 40 years ~ (22) s
LA 0
24
AspAT 0 24
LDH 0
24
2i.1 10.4 27.9 i5.1
16.9 7.5 i9.0 8.4
19.4 il.7 24.8 8.0
118 52 125 37
t29 63 152 41
26.4 16.7 35.7 i0.5
LDH 1 0 24 55 16 66 3i
62 29 72 32
P < 0.05
clinical s y m p t o m s or E C G changes, t h e m e a n a c t i v i t y of t h i s e n z y m e a t t h e 2 4 t h h r of o b s e r v a t i o n was twice as high as t h e u p p e r l i m i t of t h e n o r m a l range. The a c t i v i t y of this e n z y m e in t h e group w i t h 2 n d a n d 3rd degree poisoning was higher t h a n in t h e p a t i e n t s in t h e g r a v e s t condition. This is p r o b a b l y caused b y g r e a t e r m o t o r a c t i v i t y in t h e p a t i e n t s w i t h less severe poisoning a n d b y a s u b s e q u e n t release of t h e e n z y m e of m u s c u l a r origin i n t o t h e serum. I n p a t i e n t s w i t h p a t h o l o g i c a l E C G tracings, biochemical changes showed significantly higher values (Table 6). T h e activities of t h e e n z y m e s u n d e r e x a m i n a t i o n d i d n o t d e p e n d on C O H b c o n c e n t r a t i o n , whereas t h e L A level was significantly h i g h e r in t h e p a t i e n t s w i t h higher C O H b s a t u r a t i o n (Table 7). As is k n o w n , t h e C O H b s a t u r a t i o n s t u d i e d on a d m i s s i o n to h o s p i t a l d e p e n d s on t h e t i m e e l a p s e d from t h e cessation of exposure to t h e t i m e blood is collected for t e s t i n g (Bogusz et al., i972). I n our p a t i e n t s t h e t i m e r a n g e d f r o m t t o 5 hrs. T h e L A level, j u s t as t h e C O H b s a t u r a t i o n , reaches its h i g h e s t v a l u e d u r i n g e x p o s u r e to c a r b o n monoxide, a n d after its cessation e x p o n e n t i a l l y drops. A m o r e precise analysis showed t h a t t h e p a t i e n t s w i t h high C O H b a n d L A values h a d been b r o u g h t (within i to 2 hrs) t o t h e Clinic c o m p a r a t i v e l y quickly. This i n t e r d e p e n d e n c e b e t w e e n
~ s
over 8 hrs (12)
~ s
~ s
~ s
~ s
symptoms ~ ECG--(17)
s y m p t o m s z E C G + (12)
s y m p t o m s I I - - I I I ~ (8)
s y m p t o m s I V ~ (10)
Clinical a p p e a r a n c e
~ s
6 to 8 hrs (18)
27.9 14.1
27.5 17.5 19.1 12.0
14.5 13.2
15.0 11.1
40.7 23.3 P < 0.001
P < 0.001
25.6 9.2
17.5 13.8
24
27.9 t3.9
26.3 11.4
10.8 4.9
0
21.2 16.3
AspAT
0
24
LA
84 47
P < 0.001
160 51
126 43
0
LDH
P < 0.001
184 54
134 40
87 50
24
P < 0.01
32.8 13.9
27.7 t0.2
24.7 6.6
20.9 12.4
21.4 10.5
14.4 8.3
13.2 7.6
P < 0.001
30.0 12.9
32.9 14.5
19.6 11.2
14.3 6.6
0
17.4 6.2
AspAT
LA
0
24
-P < 0.05
33.6 14.4
50.6 19.2
27.1 13.4
22.3 12.9
24
t33 59
138 61
120 41
108 32
0
LDH
P < 0.01
163 63
i65 68
142 36
112 30
24
T a b l e 5. R e s u l t s of i n v e s t i g a t i o n s in t h e s u b g r o u p s divided a c c o r d i n g to clinical p i c t u r e
~ s
u p to 6 hrs (17)
T i m e o f exposition
79 26
80 31
45 26
24
52 30
42 19
53 24
112 30
84 31
41 22
49 31
24
P < 0.001 P < 0.001
101 41
0
LDH 1
P < 0.05 P < 0.01
70 31
69 30
45 26
0
LDH~
Table 4. T h e r e s u l t s of i n v e s t i g a t i o n s in t h e s u b g r o u p s divided according to t h e l e n g t h of e x p o s u r e
oq
~.
o
P < 0.01
P < 0.01
P < 0.01
26.2 t2.8
20.6 9.6
12.3
7.6
6.2
28.2
14.3
13.2
s
6.6
s
AspAT 0
24
~
17.4
~
No c h a n g e s (17)
C h a n g e s p r e s e n t (30)
LA 0
C h a n g e s in E C G curve
P < 0.01
35.5 17.0
12.9
22.3
24
129 58
3t
108
LDH 0
P < 0.01
155 57
29
t12
24
Table 6. T h e relationship b e t w e e n biochemical a n d electrocardiographical c h a n g e s
64 32
24
53
LDH1 0
P < 0.02
76 38
31
49
24
7~
Two Types of Carbon Monoxide Poisoning
t47
Table 7. The relationship between biochemical changes and COHb saturation COHb saturation up to t5% (30) above 15% (t7)
LA ~ s :~ s
AspAT
LDH
0
24
0
24
0
20.8 I0.8 30.5 13.3
t6.6 8.4 20.1 7.2
22.1 14.6 21.6 8.8
29.6 t3.0 32.7 15.7
120 48 t25 30
LDH1 24"
139 48 139 43
b
24
59 24 61 40
64 39 71 37
P < 0.01
the time of patient transport and LA level had not been revealed until the present studies, in which the time of patient transport was sometimes as long as 5 hrs. The biochemical findings in 8 pairs of patients poisoned in shared rooms are presented in the Table 8. This data revealed that even under like exposure to carbon monoxide biochemical changes may differ. Some dependence on age of patient is observed. A comparison of degree of change in our patients and those previously studied who were poisoned by lighting gas shows that the changes produced by coalstove gas are more intense, probably due to a greater length of exposure (Table 9). I n an attempt to evaluate the condition of patients and the clinical course of poisoning, based on the biochemical parameters studied, t i cases were selected from the material under investigation in whom at least two of four criteria were fulfilled: i. LA-O concentration exceeding three times the upper limit of the normal values, 2. AspAt-24 activity exceeding three times the upper limit, 3. LDIt-24 activity exceeding twice the upper limit, 4. LDHx-24 activity exceeding twice the upper limit. Of these I i patients, 9 were in very critical condition on admission (4th degree), and 2 patients were in critical condition (3rd degree). There patients died while treated, and in 4 patients some complications developed during treatment (broncho-pneumonia, psychoorganic syndrome). The time of treatment in this group (excluding cases that ended in death) was t0 to 41 days - - an average of 32 days. Of the remaining 36 patients who did not fulfiill the established criteria, 17 patients did not show any poisoning changes or changes in ECG; in 12 of them only changes in ECG were found; 6 patients were in moderately critical condition (2rid degree); and i patient was in very critical condition (4th degree). This patient (80 years old) developed a complication in the form of pneumonia. I n the remaining patients the treatment ran its course without complicatic as. The period of treatment
M. Bogusz et ul.
148
Table 8. Biochemical changes in 8 pairs of patients, poisoned in shared rooms Sex
Age
Symptoms
ECG
LA-O
AspAT-24LDH-24
LDH1-24
F M F M F M F IV[ F M F M F M F M
77 82 24 29 74 70 22 24 33 32 52 20 48 21 50 18
~ ~ III~ III~ II ~ I~ IV ~ IV ~ ~ ~ II ~ ~ ~ ~ III~ II ~
+ + + + + + + + + + + + --+ +
16.9 16.7 23.2 23.0 27.5 36.6 36.2 31.8 19.9 21.1 36.2 30.7 26.4 18.8 24.8 20.2
12.1 12.0 115.0 82.0 27.2 24.0 79.0 48.6 17.3 21.8 25.6 19.6 24.0 18.0 38.8 26.0
88 48 96 99 49 50 138 103 48 47 47 29 49 37 t31 73
148 106 190 279 100 1t4 288 267 72 133 113 85 77 78 173 151
Table 9. Enzyme activities and lactate level in lighting gas and coal-stove-gas poisoning. The results are expressed in relative values: upper limit of normal values = I LA-O
AspAT-24 LDI-L24
LDH1-24
lighting gas (47) ~ s
t.2 0,8
2.0 1.6
0.8 0,3
0.9 0.5
coal-stove gas (47)
1.7 0.8
2.6 1.7
1,0 0.5
1.3 0.4
~ s
ranged from 4 to 40 days and averaged t0 days. It was significantly s h o r t e r t h a n t h e t i m e of t r e a t m e n t i n t h e p r e c e d i n g g r o u p ( P < 0,001). Summing up the present studies, it can be stated that their results d i d n o t d i f f e r q u a l i t a t i v e l y f r o m t h o s e o b t a i n e d i n t h e g r o u p of p a t i e n t s with lighting-gas poisoning. Regarding enzymatic and ECG changes, similar data for lighting gas were presented by :French authors (Bour et al., 1 9 6 2 ; D u p l a y et al., 1 9 6 7 ; B o u l e t r e a u , 1 9 7 0 ; T h i e l s et al., 1972), a n d A y r e s et al. ( t 9 7 0 ) s h o w e d s i m i l a r c h a n g e s i n l a c t a t e l e v e l i n t h e i r i n v e s t i g a t i o n s . I t s h o u l d b e a d d e d t h a t t h e a l k a l i z a t i o n t r e a t m e n t of t h e p a t i e n t , r e c o m m e n d e d b y B u r m e i s t e r a n d N e u h a u s (1970) w a s also a p p l i e d . I t c o n t r i b u t e d t o a r a p i d c o n t r o l of d i s t u r b a n c e s i n a c i d - b a s e b a l a n c e , w h i c h w e r e r e f l e c t e d i n o u r s t u d i e s b y a h i g h l a c t a t e level.
Two Types of Carbon Monoxide Poisoning
~49
Conclusions 1. B o t h i n lighting-gas poisoning a n d in poisoning b y coal-stove gas, t h e lactate level a n d AspAt, L D H , a n d L D H 1 activities reach the highest values on the 2 n d d a y of t r e a t m e n t . 2. E n z y m a t i c changes increase as time of exposure to coal-stove gas is l e n g t h e n e d ; in addition, these changes are more intense in elderly patients. 3. E n z y m a t i c changes a n d those i n lactate level occur parallel to clinical a n d ECG changes. The A s p A t a c t i v i t y is increased e v e n i n cases in which there are no clinical s y m p t o m s or changes in ECG. 4. A t r i p l e - t h e - n o r m a l lactate level on admission is absolute i n d i c a t i o n for hospitalization. A threefold increase i n A s p A t a c t i v i t y on t h e second d a y of t r e a t m e n t is connected with severe poisoning a n d s t r o n g l y indicates complications.
References Auvinen, S., Konttinen, A. : The diagnostic value of serum LDtt isoenzymes and heat-stable and urea-stable LDH measurements. Acta med. scand. 189, 191 --198 (t971) Ayres, S., Gianelli, S., Mueller, H. : Myocardial and systemic responses to carboxyhemoglobin. Ann. N.Y. Acad. Sci. 174, 268--293 (1970) Bogusz, M., Cholewa, L., Mlodkowska, K., Pach, J. : Biochemical criteria of hypoxia in acute carbon monoxide poisoning. J. Eur. Toxicol. 5, 306--309 (1972) Bouletreau, P. : L'intoxication aigue par l'oxyde de carbone. Paris: Masson 1970 Bour, H., Doroux, P., Glimet, T., Cluvel, H.: Les enzymes du muscle an du coma oxycarbon~e. Sem. HSp. Paris 88, 3152--3156 (1962) Burmeister, H., Neuhaus, G. : Die Behandlung der schweren subakuten Leuchtgasvergiftung beim Menschen. Arch. Toxicol. 26, 277--292 (1970) Duplay, H., Ziegler, G., Gard, A., Pinto, J. : Valeur prognostique des transaminases dans les intoxications par l'oxyde de carbone. Presse m6d. 75, 469--473 (1967) Pach, J. : The prognosis and outline of treatment in acute carbon monoxide poisoning. Folia reed. craeov. (1974) (in press) Thiels, H., Van Dorme, J., Vermeire, P.: Modifications electro-cardiographiques immediates et tardives au cours de l'intoxication oxycarbonne aigue. Lille m4d. 17, t91--198 (1972) Wroblewski, F., Gregory, K. : Lactic dehydrogenase isozymes and their distribution in normal tissues and plasma and in disease states. Ann. N.Y. Acad. Sci. 94, 912--937 (1961) Prof. Dr. Leon Cholewa Dr. med. Maciej Bogusz Dr. med. Janusz Pach Institute of Forensic Research 31033 KrakSw, Westerplatte 9, Poland Toxicological Clinic Institute of Internal Medicine Academy of Medicine, Krak6w, Poland Mgr Ksenia Mtodkowska Department of Clinical Chemistry Institute of Internal Medicine Academy of Medicine, KrakSw, Poland
