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Acute heat stroke deaths
Pathology ( 1 9 X 1 ) . 13, pp. 14.5 56
ACUTEHEATSTROKE DEATHS TZEEC. CHAO,*R. SINNIAH?AND J . E. P A K I A M ~ * Department of Pathology, Ministry of Health, Sirigaporc. and DcJprirtn?icvitcof
i- Pathology and $Geography, Univcvsiti, of Singaporr
Summary Ten cases of death due to heat stroke are described. They were all young men who collapsed during running exercise or route march and died in hospital later. Postmortem examination was carried out in all cases. Death was due to disseminated intravascular coagulation with widespread microthrombus formation and coagulative necrosis involving many organs. Meteorological studies showed that at the time of the collapse the environmental temperature was higher than average although it may have been in the morning or evening.
Key Wordx; heat stroke, DIC, ambient temperatures, Singapore
INTRODUCTION Acute heat stroke in causing thermal injury a t cellular level can result in widespread damage to the heart, liver, kidney and blood coagulation system.' Damage to the vascular endothelium may initiate platelet aggregation leading to disseniinated intravascular coagulation (DIC).' I t is a n acute medical emergency. Without prompt recognition and immediate treatment by cooling and other supportive measures, the mortality rate is likely to be high. Though many of the victims in reported series were over 50 yr old and were killed in heat waves affecting cities in the temperate zone, a significant proportion of cases were young healthy adults such as military personnel, miners, labourers o r athletes, doing hard physical work in a hot moist atmosphere.3Known risk factors that predispose to heat stroke include ( 1 ) fatigue, (2) lack of physical conditioning, (3) failure of acclimatization, (4) previous illness. ( 5 ) obesity, (6) increased Wet Bulb Globe Temperature (WBGT) Index derived by addition of 70'%,of the naturally convected wet bulb temperature to 20';:, of the black-globe (radiant) temperature and 10% of the dry-bulb temperature as a means of assessing the probable effect of environment.3.4
MATERIALS AND METHODS In Singapore, no record ol'death due to heat stroke was recorded prior to 1974. perhaps because o f failure to report these cases to the coroner. From 1974 to 1979, 10 such deaths were reported to the coroner and investigated hy post-
146
CHAO
TAHLt
I
et ul.
Pathology (1981), 13, January
Circuni\tdnces of death Time and date of collapse
Time interval from collapse to death 21
7
niin
1645 hrs 29,'3174
20
66 h 10 min
1125 Iirj 7'5'75
18
1 h 35 min
1820 hrs 2814 76
18
99 h 5 min
1745 hrs l3/8,76
11 20
~~
5
1
______ 590:77
well built
19
29
166
73.2
57 h 10 min
1210 hrs 5/4:77
Collapsed at road rally
67 h 35 min
0930 hrs 2616 77
_____~_______
=I: 10
.______~
Collapsed after 5 mile run
-~
I9
165
64.8
Collapsed at running exercise
24
1 15
51.3
Collapsed during 8 km run
18
160
53.3
Collapsed during 5 km run
10 h 20 min .____.
45 mm
I700 hrs 2/5/77
_____ 0820 hrs 7/3/78
~~
44 h 25 min
1900 hrs
37 h 40 min
22 I0 hrs I 1 16'79
_.
997 79
19
180
56.2
Collapsed during 10 km run
7\5/79
mortem examination. Nine of these cases were in National Service men with ages ranging from 18 to 24 yr. The tenth victim was a 29-yr-old man who collapsed during a road rally (Table 1). In all cases the organs were examined by light microscopy and in 2 by immunofluorescence microscopy.
RESULTS Clinical findings
All the victims collapsed during or after physical exercise like running or a route march and were hospitalized. The interval from time of collapse to time of death varied from 45 min to 99 h 10 niin. In 5 cases, clinical notes were available for further analysis. At time of admission, the rectal temperature ranged from 40°C to 42°C. All patients were sweating profusely and had diarrhoea. Four were in a state of coma while the fifth was delirious and in convulsions. The pulse rate was rapid, with blood pressure ranging from normal to hypotension. The serum electrolytes were within the normal range but all of them exhibited evidence of disseminated intravascular coagulation (DIC) with low platelet counts, prolonged partial thromboplastin time (PTT) and prothrombin time (PT) (Table 2). All 10 patients died from the bleeding diathesis of DIC.
ACUTE HEAT STROKE DEATHS
147
T A R L2 ~ Clinical findings in 5 cases
Rectal temperature Level of consciousness Diarrhoea Sweating Pulse ratc Blood pressure (mm Hg) Serum K' nimol/l N a + mmol I C1 mmol,l Urca tnmol:l Platelets (per mm') PTT sec PT sec DIC
550!74
1281 176
Autopsy no 590177
1438177
760179
42 C Coma
40 C Coma Ill
40 C Drowsy Fits
40 C Com'i Ill
40.5 c Coma Ill
111
+ +
IOOirnin 110170 36 I20 I08 76 65.000 3.300 3.300
+
+ +
I56/min I 0Oi30-l00,70 46 I35 95
91 3 1.000 3. 100 48 1
+
+ +
lOO/min 90160- 1 I0!80 50 145 99 15 i 65,000 70 4 -41 1
+
+ +
120 min 90 50 120180 45 140 99 70 ~
~
~
+
f f
2001inin 90/50- 100;70 3.0 I45 105 5.3 90,000 > 120 25
+
Gross post - m oY tern findings
At post-mortem, it was found that except for one underweight youth, all bodies were well nourished with 4 clearly overweight. The most striking finding in all cases was the presence of pulmonary haemorrhages. These were large areas of diffuse haemorrhage into the parenchyma with blood stained fluid in the trachea and bronchi. Nearly all had had frank haemoptysis clinically. There was no-evidence of pulmonary embolism. The brains were generally congested and oedematous with petechial haemorrhages into the white matter in focal areas. In the most severe case there was diffuse haemorrhage into the basal ganglia on both sides with secondary pontine haemorrhage. Obvious areas of infarction were observed in one case. Diffuse mucosal haemorrhages in the stomach, duodenum and small intestines were found in 7 cases (Fig. 1). Clinically there had been haematemesis and inelaena prior to death in these cases, and at post-mortem the stomach and small intestines were filled with blood clots. Haemorrhages in the myocardium, either diffuse and petechial or more severe and localized in the A-V node region, and haemorrhages into the renal pelvis provided further evidence of a generalized bleeding diathesis. In 2 cases there were adrenal haemorrhages and in 2 others cutaneous manifestations of bleeding with ecchymoses. Another striking change was fatty change in the liver. This varied from congestion and mild fatty change to severe fatty change with a soft yellowish liver parenchyma. Histopathologj Light microscopic examination showed haemorrhages in many organs, most marked in the lungs and gastrointestinal tract. There were also prominent focal haemorrhages in the brain and adrenal glands. Widespread microthrombi were found in the capillaries and smaller arterioles in the lungs, kidneys, adrenals, brain (Fig. 2), and other organs. Sludging of red blood cells was observed in the capillaries and arterioles of many organs. Sections of the heart showed focal areas of coagulative necrosis of the myocardial fibres (Fig. 3) in all 10 cases. Associated with the areas of coagulative necrosis were focal areas of haemorrhage within the myocardium and in the subendocardium. The kidneys showed focal
148
CHAO
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Pathology (1981). 13, January
FIG I Specimen of stomach, duodenum and jejunum showing massive mucosal haeiiiorrhages
FIG 2 Section o f brain showing microlhrombi (arrows) and sludging of red blood cells in the small blood vessels. Martius Scarlet blue stain x 400
ACUTE HEAT STROKE DEATHS
149
FIG. 3 Scction of heart showing Focal area of coagulative necrosis 01' the myocardium, with loss of nuclei and clumping of cytoplasmic protein. Mauson trichrome x 640
areas of haemorrhage, with microthrombi in the glomerular capillaries and arterioles i n 5 o f the 10 cases. The proximal tubules showed focal areas of coagulative necrosis, with clumping of the proteins in the tubular epithelial cells (Fig. 4). The liver showed varied pathological changes including centrizonal necrosis, haemorrhage, cholestasis and mild to severe f a t t y change. The Fatty change in the liver was graded 1 + to 3 +, according to the degree of severity (Fig. 5). Steatosis o r fatty change in the liver was observed mainly around the centrilobular areas, and was found in 5 of the 10 cases. Congestion and focal haemorrhagic areas were seen in the splenic pulp. Focal infarction o f t h e pituitary gland was round in one case. Details of the histopathological changes in the various organs are shown in Table 3. The skin biopsies showed the presence of normal sweat glands and skin appendages in all the patients. lrnniunt~fluorc~scrnce microscopy studies were performed in 2 cases. Sections of brain, liver, lungs, kidneys. adrenals, skin and heart were tested against anti-human IgG, IgA, IgD, IgE, IgM, C,, C,,, C, and fibrin-fibrinogen by standard procedures described previously.5 There were n o deposits of immunoglobulins and complement of any significance in these organs. Fibrin thrombi were found in the glomerular capillaries and the arterioles of the kidneys, brain and adrenals, and in the alveolar capillaries of the lungs (Fig. 6).
Metrovologicul fuctors ,
An attempt was made to find out the meteorological condition a t the time ofcollapse ofthese 10 men. The ambient air temperature, relative humidity and mean wind velocity a t the time
150
CHAO et
GI.
Pathology [ 1981). 13. January
Flc;. 4 Section of kidney showing coagulative necrosis of' the proximal tubules. with clumping of proteins in the tubular epithelial cells (arrows). Masson trichromc x 400
FIG. 5 Liver section showing varying degrees of fatty change. This section shows severe grade 3 fatty change and mild periportal fibrosis. No history o f alcoholism. and no alcoholic hyaline in the liver tissue. H & E x 100
+,
~
550 74
847 75
634 76
1281 76
590 17
1098 7 1
1438 7 1
355 7x
760 79
997 79
1
2
3
4
5
6
7
8
9
10
Case no
4utops\ no -___ Lungs
Coagulatike necrow
Coagulative necrosis
Moderate fatty change grade 2 + Centrizonal necrosi\ Centrizonal necrosi\
Haemorrhages
Coagulative necrosis with haemorrhages Coagulative necrosis. Haemorrhage\ Coagulative necrosis
Thrombi. Sinusoidal congestion Haemorrhages Mild fatty change Thrombi grade 1 + Spotty liver cell necrosis Thrombi. Mild fatti change Haemnrrh;igcs. grade I +. Bronchopneumonia Centrizonal necrosic
Severe haemorrhages
Haernorrhage5. Thrombi
Centrizonal necrosis with haemorrhages
Haemorrhages. Thrombi
Moderate fatty change grade 2 + . Centrizonal necrosis Cholestasis
Mild fatty change grade 1 + Centrizonal necrosis Severe fatty change grade 3 t
Centrizonal necrosis
Liver
Coagulative necrosis
Coagulative Haemorrhages necrosis. Subendocardial haemorrhageh Coagulative Severe necrosis. haemorrhages Foci of haemorrhages
Coagulative Haemorrhages necrosis. Su bendocardial haeinorrhages Coagulative Severe haemorrhages necrosis
Heart
T , ~ B L3F Histopathological changes
-
Haemorrhage'
Thrombi Haemorrhagca
Spleen
Tubular necrosis. Thrombi
Tubular necrosis. Thrombi. Focal haemorrhages Tubular necrosis. Thrombi. Haemorrhageb Tubular necrosis. Thrombi Tubular necrosis. Haemorrhage\ Tubular necrosis. Thrombi Tubular necrosis. Haeniorrhage\ :'on gest ion
Fongestion
Congestion
Congest ion
Congestion
Haemorrhager
Congestioii
Tubular Congestion necrosis. Haemorrhagei
Tubular necrosis. Foci o f . haemorrhage\ Tubular necrosis
Kidnej
Thrombi. Focal haeinorrhages
Thrombi Congestion
Congestioii
Normal
Thrombi. Haemorrhage\
Congestion
Thrombi. Congestion
Focal haemorrhage\
Foci of haeinorrhages. Thrombi
Brain
Pituitary infarct
Others
-hrombi 'ongestion
'ongestion
haemorrhage in gut
Submucosal
Mucosal haemorrhages in gut 4 aemo rrhage\ Mucosal haemorrhage5 in gut
qecrosis
Toiigest ion
:'ongestion
Adrenal5
v1
-
-
5
z
4 >
ci
iP%
5rc
>
152
CHAO
('t
(11.
FIG. 6
Pathology (1981). 13, January
Iinintinofluoresccnce microscopy of the lung showing fibrin thrombi in
t h e nlveolar capillaries. x 350
of collapse were obtained. The maximum temperature recorded during the day and minimum relative humidity were also noted. The time of day when collapse occurred ranged froin 8.20 a.m. to 10.10 p.m. The average values of monthly rainfall, sunshine, amount of cloud, scalar wind, relative humidity and temperature are plotted in Fig. 7. The climate of Singapore is controlled by 2 monsoons. The S-W monsoon from May to August is accompanied by slightly warmer temperature, lower wind speeds, more sunshine and less rainfall. The N-E monsoon from November to February is cooler, with higher wind speeds, less sunshine and high rainfalls. The inter-monsoon periods of March to April and September to October are transition months, with weather which may vary from year to year depending on the strength of the monsoon. On the average. their weather is more closely associated with that of the S-W monsoon. The temperature at the time of collapse and the maximum recorded during the same day were plotted on the background of the mean temperature data for the respective months (Fig. 8). I t should be noted that the maximum temperatures of all the days o n which heat stroke occurred were above the average mean, and in 7 they were above the mean maximum. The temperatures at the time of collapse were above the mean average in 7 cases. All 10 deaths occurred during the hotter months of March to September, that is, the S-W monsoon and the inter-monsoon periods.
ACUTE HEAT STROKE DEATHS tat. 1 ' 2 2 ' ~ 105' M . S . L . L0ng.103~55'E
SINGAPORE A I R P O R T
300
Mean Rainfall
J
F
M
A
M
J
J
A
S
d
.. 300
D
N
250
.. 250
200
.. 200
150
.-1 5 0
(m)
7
Mean Sunshine (hours)
7
6
6
5 4
hunt Of
cloud
4
90
.-90
80
.-80
10
.. 70
2
M a n wind speed
2
(m/s)
1
Mean Relative Humidity
(%I
Air Temp (OC)
1
-- 90
90
32
-- 80 -- 32
30
-- 30
28.
--
26.
-- 26
80
--
24 22
J
F
M
A
M
j
j
A
M O N T H
FIG. 7
Meteorological data of Singapore
f
d
i
d
'
28
24
22
153
154
CHAO
et a1
Pathology (1981), 13, January A I R TEMPERATURE N
N P
C N n
(OC)
s
N
m
W
N
x
0
I
X
z
FIG. 8 Temperatures at time and day of collapse compared with mean m o n t h l y temperatures
P W
4
ACUTE HEAT STROKE DEATHS
155
DISCUSSION Classically, the diagnosis of heat stroke rested upon (1) proven exposure to high environmental temperature, and the presence of (2) hyperpyrexia of over 41.1 "C, (3) hot, dry skin and (4) central nervous system signs.' However, subsequent investigations showed that these diagnostic yardsticks were inadequate. Heat stroke cases were found to occur under comparatively mild environmental conditions and in the early morning of relatively cool days. The duration of the physical exertion could be brief. Profuse sweating might occur and the recorded body temperature need not be above 41.1 "C.7These observations have been borne out by the present series. Eight of our cases occurred either in the morning or evening. The physical exertion was not exceptionally hard. The rectal temperature recorded was between 40°C to 42°C and all victims sweated profusely and had diarrhoea. Death in heat stroke cases has been reported as due to renal failure, hepatic failure, hyperkalaemia, cardiovascular collapse, haemorrhagic diathesis or a combination of these features. Damage to the kidney manifested itself as proteinuria, raised blood urea and acute renal failure. The renal lesions were thought to be at least partly due to direct thermal injury with coagulative necrosis of the tubular epithelium as the majority of the patients were not hypotensive or obviously dehydrated, and the raised blood urea level persisted in spite of intravenous therapy.8, The liver damage showed centrilobular degeneration and necrosis with dilatation of centrilobular sinusoids and central veins and cholestasis. Ultrastructural changes included degenerative changes or desquamation of sinusoidal cells, ballooning or flattening of microvilli, break in hepatocyte outer membranes and electron-lucent vacuoles along the sinusoidal border.". ' I In our cases, besides the centrizonal necrosis and cholestasis, there was fatty change ranging from mild to severe. This fatty change has not often been mentioned in other series. This could be due to (a) increased adipose fat breakdown by hyperpyrexia and (b) thermal damage to liver mitochondria resulting in inability t o mobilize Fat. Widespread coagulative necrosis was observed by us in the heart, liver, kidney and other organs. This manifested itself as clumping of the cytoplasmic protein as a result of hyperpyrexia. The cytoplasmic protein was simply cooked and coagulated. This phenomenon had been observed earlier in animal experiments.'* All the patients in this series died from disseminated intravascular coagulation, a s demonstrated by the clinical manifestation of bleeding diathesis and pathological changes of widespread microthrombus formation in various organs like brain, lungs, kidney, adrenals and pituitary gland. There were massive haemorrhages into the lungs, gastrointestinal tract, kidney, brain and other organs. The haemorrhages in heat stroke had been variously attributed to increased capillary permeability," hypoprothrombinaemia and thrombocytopenia,' increased fibrinolysis,' hypofibrinogenesis and excessive fibrinoly~is'~ and consumptive coagulopathy." The observation of widespread microthrombus formation supported the theory of DIC being due to endothelial damage which caused platelets to aggregate and triggered the clotting mechanism. Obstruction of small vessels led to infarcts and necrosis of the various organs. The damaged tissues released plasminogen activator and the resulting fibrinolysis reduced fibrinogen levels. The incoagulability of the blood contributed to further bleeding from the previously damaged tissues.* Analysis of the meteorological conditions at the time of collapse showed that in 7 of 10 cases the temperature exceeded the mean temperature for the month in which death occurred and similarly in 7 of 10 cases the maximum temperature during the day of collapse exceeded the average maximum temperature for the month. The time of collapse was recorded as
'
156
rt d.
CHAO
Pathology ( I Y X I ) , 13, January
between 4.00 p.m. and 7.00 p.m. in 5 cases. Of these, 3 occurred when both the temperature at time ofcollapse and maximum temperature during the day exceeded the average mean and maximum respectively. In the remaining 2 cases the temperature at time ofcollapse exceeded the average mean temperature. One victim was a new recruit drafted 6 d earlier. One case occurred between 10.00 p.m. a n d 1 1.OO p.m. Though the day had been hot, the temperature a t the time ofcollapse was below the mean. This patient had a history of another collapse due to heat stroke one mth previously. Three cases occurred in the morning, in 2 instances the morning was hot. The remaining case occurred between 12 noon and 1.00 p.m. on a comparatively cool day; however the patient had been ill for the past 3 days. These observations support the fact that uncomfortable environmental conditions, previous illness, failure of acclimatization in the presence of physical exercise can lead to heat stroke. Attention to these factors in the training of new recruits could reduce its incidence. I t appears that the major factors leading to death are massive bleeding due to DIC and coagulative necrosis involving many major organs. Death is caused by multifactorial mechanisms.
ACKNOWLEDGEMENTS We thank the technicians of the Government and University Departments of Pathology for technical assistance, M r T. C. Tan for the photography, and Mrs T. H. K o h for typing the script. Addrc.s.s f h r c.orrc,sijond~,nc.r..T.C.C.. Department of Pathology, Ministry of Health, Singapore
References 1 . MAIAML!~. N.,H A Y M A K EW. R , & CUSIER, R. P. (1946): Heat stroke: a clinicopathological study o f 125 fatal cases. Milit. Surg. 99, 397-449.
2. SOHN R. S., SIJN,S. C., COIC‘OL.OUGH, H. L. u l . ( 196X): Heat stroke: an electron microscopic study
of endothelial ccll damage and disseminated intravasculnr coagulation. A r c h . Intern. Med. 122,
43 47.
3. G ~ o w h s ,G . H. A. J R & O’DONNLLL, T. F. J R (1974): Heat stroke-current concepts. N . EngI. J . Mid. 291, 564 566. T. F. J K (1975): Acute heat stroke4. O’DONNF.LI., epidcmiologic. biochemical, rcniil and coagulative 5ludies. J A M A 234, 824 828. 5. S I N N I A HR., , PWEL,H. S. & LIM, C. H. (1976): Glomerular lesions in asymptomatic microscopic haematuria discovered on routine medical examination. C’lin. N q h r o l . 5, 216-228. J . W. (1956): Observation 6. AIJSTIN, M. G. & BERRY, on onc hundred cases of hcat stroke. J A M A 161, 1525 1529.
7. ~~llI3OLF:T,S., COLL, R., GIL.AT, T. & SOHAR,E. (1967): Heat stroke: its clinical picture and mechanism in 36 cases. Q. J . Mcd.36, 525-548. 8. Ktw. M C., ARRAHAMS, C., LFVIN,M. W. ef a/. (1967): The effects of heat stroke on the function and structure of the kidney. Q. .I. Med. 36, 277 -300.
9. KNOCIIFL. .I.P., B H S ~ LW. , R.. HERNIXIN. E. G. iv d. (1961): The renal, cardiovascular, haemato-
logic and serum electrolyte abnormalities of hcat stroke. Am. .J. Mrd. 30, 299-309. , KENT.G. 10. KEW, M. C., BERSOIIN, I . , S E ~ T ~H.L & (1970): Liver damage in heat stroke. An?. J . M d 49, 192-202. 11. KEW, M. C., MINICK,0. T.. BAHU, R. M. c / ul. (1978): Ultrastructural changes in the liver in heat stroke. A m . J . Puthol. 90, 609-618. L. V. (1954): Heat death. S I .An?. 12. HEILBRUNN, 190, 4-70. 13. WRIGHT,D. O., REPPERT,L. B. 8r CUTTINO, J. (1946): Purpuric manifestation of heat stroke: studies of prothrombin and platelets in twelve cases. Arch. Intern. Med. 77, 27-36. J. R. (1967): 14. MEIKLE,A. W. & GKAYHILL, Fibrinolysis and hemorrhage in a fatal case of heat stroke. N . Engl. J . Med. 276, 911-913. 15. WERER,M. B. & BLAKELY, J. A . (1969): The haemorrhagic diathesis of heat stroke: a consumptive coagulopathy successfully treated with Heparin. Luncer i, I 1 90-1 192.
ACUTEHEATSTROKE DEATHS TZEEC. CHAO,*R. SINNIAH?AND J . E. P A K I A M ~ * Department of Pathology, Ministry of Health, Sirigaporc. and DcJprirtn?icvitcof
i- Pathology and $Geography, Univcvsiti, of Singaporr
Summary Ten cases of death due to heat stroke are described. They were all young men who collapsed during running exercise or route march and died in hospital later. Postmortem examination was carried out in all cases. Death was due to disseminated intravascular coagulation with widespread microthrombus formation and coagulative necrosis involving many organs. Meteorological studies showed that at the time of the collapse the environmental temperature was higher than average although it may have been in the morning or evening.
Key Wordx; heat stroke, DIC, ambient temperatures, Singapore
INTRODUCTION Acute heat stroke in causing thermal injury a t cellular level can result in widespread damage to the heart, liver, kidney and blood coagulation system.' Damage to the vascular endothelium may initiate platelet aggregation leading to disseniinated intravascular coagulation (DIC).' I t is a n acute medical emergency. Without prompt recognition and immediate treatment by cooling and other supportive measures, the mortality rate is likely to be high. Though many of the victims in reported series were over 50 yr old and were killed in heat waves affecting cities in the temperate zone, a significant proportion of cases were young healthy adults such as military personnel, miners, labourers o r athletes, doing hard physical work in a hot moist atmosphere.3Known risk factors that predispose to heat stroke include ( 1 ) fatigue, (2) lack of physical conditioning, (3) failure of acclimatization, (4) previous illness. ( 5 ) obesity, (6) increased Wet Bulb Globe Temperature (WBGT) Index derived by addition of 70'%,of the naturally convected wet bulb temperature to 20';:, of the black-globe (radiant) temperature and 10% of the dry-bulb temperature as a means of assessing the probable effect of environment.3.4
MATERIALS AND METHODS In Singapore, no record ol'death due to heat stroke was recorded prior to 1974. perhaps because o f failure to report these cases to the coroner. From 1974 to 1979, 10 such deaths were reported to the coroner and investigated hy post-
146
CHAO
TAHLt
I
et ul.
Pathology (1981), 13, January
Circuni\tdnces of death Time and date of collapse
Time interval from collapse to death 21
7
niin
1645 hrs 29,'3174
20
66 h 10 min
1125 Iirj 7'5'75
18
1 h 35 min
1820 hrs 2814 76
18
99 h 5 min
1745 hrs l3/8,76
11 20
~~
5
1
______ 590:77
well built
19
29
166
73.2
57 h 10 min
1210 hrs 5/4:77
Collapsed at road rally
67 h 35 min
0930 hrs 2616 77
_____~_______
=I: 10
.______~
Collapsed after 5 mile run
-~
I9
165
64.8
Collapsed at running exercise
24
1 15
51.3
Collapsed during 8 km run
18
160
53.3
Collapsed during 5 km run
10 h 20 min .____.
45 mm
I700 hrs 2/5/77
_____ 0820 hrs 7/3/78
~~
44 h 25 min
1900 hrs
37 h 40 min
22 I0 hrs I 1 16'79
_.
997 79
19
180
56.2
Collapsed during 10 km run
7\5/79
mortem examination. Nine of these cases were in National Service men with ages ranging from 18 to 24 yr. The tenth victim was a 29-yr-old man who collapsed during a road rally (Table 1). In all cases the organs were examined by light microscopy and in 2 by immunofluorescence microscopy.
RESULTS Clinical findings
All the victims collapsed during or after physical exercise like running or a route march and were hospitalized. The interval from time of collapse to time of death varied from 45 min to 99 h 10 niin. In 5 cases, clinical notes were available for further analysis. At time of admission, the rectal temperature ranged from 40°C to 42°C. All patients were sweating profusely and had diarrhoea. Four were in a state of coma while the fifth was delirious and in convulsions. The pulse rate was rapid, with blood pressure ranging from normal to hypotension. The serum electrolytes were within the normal range but all of them exhibited evidence of disseminated intravascular coagulation (DIC) with low platelet counts, prolonged partial thromboplastin time (PTT) and prothrombin time (PT) (Table 2). All 10 patients died from the bleeding diathesis of DIC.
ACUTE HEAT STROKE DEATHS
147
T A R L2 ~ Clinical findings in 5 cases
Rectal temperature Level of consciousness Diarrhoea Sweating Pulse ratc Blood pressure (mm Hg) Serum K' nimol/l N a + mmol I C1 mmol,l Urca tnmol:l Platelets (per mm') PTT sec PT sec DIC
550!74
1281 176
Autopsy no 590177
1438177
760179
42 C Coma
40 C Coma Ill
40 C Drowsy Fits
40 C Com'i Ill
40.5 c Coma Ill
111
+ +
IOOirnin 110170 36 I20 I08 76 65.000 3.300 3.300
+
+ +
I56/min I 0Oi30-l00,70 46 I35 95
91 3 1.000 3. 100 48 1
+
+ +
lOO/min 90160- 1 I0!80 50 145 99 15 i 65,000 70 4 -41 1
+
+ +
120 min 90 50 120180 45 140 99 70 ~
~
~
+
f f
2001inin 90/50- 100;70 3.0 I45 105 5.3 90,000 > 120 25
+
Gross post - m oY tern findings
At post-mortem, it was found that except for one underweight youth, all bodies were well nourished with 4 clearly overweight. The most striking finding in all cases was the presence of pulmonary haemorrhages. These were large areas of diffuse haemorrhage into the parenchyma with blood stained fluid in the trachea and bronchi. Nearly all had had frank haemoptysis clinically. There was no-evidence of pulmonary embolism. The brains were generally congested and oedematous with petechial haemorrhages into the white matter in focal areas. In the most severe case there was diffuse haemorrhage into the basal ganglia on both sides with secondary pontine haemorrhage. Obvious areas of infarction were observed in one case. Diffuse mucosal haemorrhages in the stomach, duodenum and small intestines were found in 7 cases (Fig. 1). Clinically there had been haematemesis and inelaena prior to death in these cases, and at post-mortem the stomach and small intestines were filled with blood clots. Haemorrhages in the myocardium, either diffuse and petechial or more severe and localized in the A-V node region, and haemorrhages into the renal pelvis provided further evidence of a generalized bleeding diathesis. In 2 cases there were adrenal haemorrhages and in 2 others cutaneous manifestations of bleeding with ecchymoses. Another striking change was fatty change in the liver. This varied from congestion and mild fatty change to severe fatty change with a soft yellowish liver parenchyma. Histopathologj Light microscopic examination showed haemorrhages in many organs, most marked in the lungs and gastrointestinal tract. There were also prominent focal haemorrhages in the brain and adrenal glands. Widespread microthrombi were found in the capillaries and smaller arterioles in the lungs, kidneys, adrenals, brain (Fig. 2), and other organs. Sludging of red blood cells was observed in the capillaries and arterioles of many organs. Sections of the heart showed focal areas of coagulative necrosis of the myocardial fibres (Fig. 3) in all 10 cases. Associated with the areas of coagulative necrosis were focal areas of haemorrhage within the myocardium and in the subendocardium. The kidneys showed focal
148
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Pathology (1981). 13, January
FIG I Specimen of stomach, duodenum and jejunum showing massive mucosal haeiiiorrhages
FIG 2 Section o f brain showing microlhrombi (arrows) and sludging of red blood cells in the small blood vessels. Martius Scarlet blue stain x 400
ACUTE HEAT STROKE DEATHS
149
FIG. 3 Scction of heart showing Focal area of coagulative necrosis 01' the myocardium, with loss of nuclei and clumping of cytoplasmic protein. Mauson trichrome x 640
areas of haemorrhage, with microthrombi in the glomerular capillaries and arterioles i n 5 o f the 10 cases. The proximal tubules showed focal areas of coagulative necrosis, with clumping of the proteins in the tubular epithelial cells (Fig. 4). The liver showed varied pathological changes including centrizonal necrosis, haemorrhage, cholestasis and mild to severe f a t t y change. The Fatty change in the liver was graded 1 + to 3 +, according to the degree of severity (Fig. 5). Steatosis o r fatty change in the liver was observed mainly around the centrilobular areas, and was found in 5 of the 10 cases. Congestion and focal haemorrhagic areas were seen in the splenic pulp. Focal infarction o f t h e pituitary gland was round in one case. Details of the histopathological changes in the various organs are shown in Table 3. The skin biopsies showed the presence of normal sweat glands and skin appendages in all the patients. lrnniunt~fluorc~scrnce microscopy studies were performed in 2 cases. Sections of brain, liver, lungs, kidneys. adrenals, skin and heart were tested against anti-human IgG, IgA, IgD, IgE, IgM, C,, C,,, C, and fibrin-fibrinogen by standard procedures described previously.5 There were n o deposits of immunoglobulins and complement of any significance in these organs. Fibrin thrombi were found in the glomerular capillaries and the arterioles of the kidneys, brain and adrenals, and in the alveolar capillaries of the lungs (Fig. 6).
Metrovologicul fuctors ,
An attempt was made to find out the meteorological condition a t the time ofcollapse ofthese 10 men. The ambient air temperature, relative humidity and mean wind velocity a t the time
150
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Pathology [ 1981). 13. January
Flc;. 4 Section of kidney showing coagulative necrosis of' the proximal tubules. with clumping of proteins in the tubular epithelial cells (arrows). Masson trichromc x 400
FIG. 5 Liver section showing varying degrees of fatty change. This section shows severe grade 3 fatty change and mild periportal fibrosis. No history o f alcoholism. and no alcoholic hyaline in the liver tissue. H & E x 100
+,
~
550 74
847 75
634 76
1281 76
590 17
1098 7 1
1438 7 1
355 7x
760 79
997 79
1
2
3
4
5
6
7
8
9
10
Case no
4utops\ no -___ Lungs
Coagulatike necrow
Coagulative necrosis
Moderate fatty change grade 2 + Centrizonal necrosi\ Centrizonal necrosi\
Haemorrhages
Coagulative necrosis with haemorrhages Coagulative necrosis. Haemorrhage\ Coagulative necrosis
Thrombi. Sinusoidal congestion Haemorrhages Mild fatty change Thrombi grade 1 + Spotty liver cell necrosis Thrombi. Mild fatti change Haemnrrh;igcs. grade I +. Bronchopneumonia Centrizonal necrosic
Severe haemorrhages
Haernorrhage5. Thrombi
Centrizonal necrosis with haemorrhages
Haemorrhages. Thrombi
Moderate fatty change grade 2 + . Centrizonal necrosis Cholestasis
Mild fatty change grade 1 + Centrizonal necrosis Severe fatty change grade 3 t
Centrizonal necrosis
Liver
Coagulative necrosis
Coagulative Haemorrhages necrosis. Subendocardial haemorrhageh Coagulative Severe necrosis. haemorrhages Foci of haemorrhages
Coagulative Haemorrhages necrosis. Su bendocardial haeinorrhages Coagulative Severe haemorrhages necrosis
Heart
T , ~ B L3F Histopathological changes
-
Haemorrhage'
Thrombi Haemorrhagca
Spleen
Tubular necrosis. Thrombi
Tubular necrosis. Thrombi. Focal haemorrhages Tubular necrosis. Thrombi. Haemorrhageb Tubular necrosis. Thrombi Tubular necrosis. Haemorrhage\ Tubular necrosis. Thrombi Tubular necrosis. Haeniorrhage\ :'on gest ion
Fongestion
Congestion
Congest ion
Congestion
Haemorrhager
Congestioii
Tubular Congestion necrosis. Haemorrhagei
Tubular necrosis. Foci o f . haemorrhage\ Tubular necrosis
Kidnej
Thrombi. Focal haeinorrhages
Thrombi Congestion
Congestioii
Normal
Thrombi. Haemorrhage\
Congestion
Thrombi. Congestion
Focal haemorrhage\
Foci of haeinorrhages. Thrombi
Brain
Pituitary infarct
Others
-hrombi 'ongestion
'ongestion
haemorrhage in gut
Submucosal
Mucosal haemorrhages in gut 4 aemo rrhage\ Mucosal haemorrhage5 in gut
qecrosis
Toiigest ion
:'ongestion
Adrenal5
v1
-
-
5
z
4 >
ci
iP%
5rc
>
152
CHAO
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FIG. 6
Pathology (1981). 13, January
Iinintinofluoresccnce microscopy of the lung showing fibrin thrombi in
t h e nlveolar capillaries. x 350
of collapse were obtained. The maximum temperature recorded during the day and minimum relative humidity were also noted. The time of day when collapse occurred ranged froin 8.20 a.m. to 10.10 p.m. The average values of monthly rainfall, sunshine, amount of cloud, scalar wind, relative humidity and temperature are plotted in Fig. 7. The climate of Singapore is controlled by 2 monsoons. The S-W monsoon from May to August is accompanied by slightly warmer temperature, lower wind speeds, more sunshine and less rainfall. The N-E monsoon from November to February is cooler, with higher wind speeds, less sunshine and high rainfalls. The inter-monsoon periods of March to April and September to October are transition months, with weather which may vary from year to year depending on the strength of the monsoon. On the average. their weather is more closely associated with that of the S-W monsoon. The temperature at the time of collapse and the maximum recorded during the same day were plotted on the background of the mean temperature data for the respective months (Fig. 8). I t should be noted that the maximum temperatures of all the days o n which heat stroke occurred were above the average mean, and in 7 they were above the mean maximum. The temperatures at the time of collapse were above the mean average in 7 cases. All 10 deaths occurred during the hotter months of March to September, that is, the S-W monsoon and the inter-monsoon periods.
ACUTE HEAT STROKE DEATHS tat. 1 ' 2 2 ' ~ 105' M . S . L . L0ng.103~55'E
SINGAPORE A I R P O R T
300
Mean Rainfall
J
F
M
A
M
J
J
A
S
d
.. 300
D
N
250
.. 250
200
.. 200
150
.-1 5 0
(m)
7
Mean Sunshine (hours)
7
6
6
5 4
hunt Of
cloud
4
90
.-90
80
.-80
10
.. 70
2
M a n wind speed
2
(m/s)
1
Mean Relative Humidity
(%I
Air Temp (OC)
1
-- 90
90
32
-- 80 -- 32
30
-- 30
28.
--
26.
-- 26
80
--
24 22
J
F
M
A
M
j
j
A
M O N T H
FIG. 7
Meteorological data of Singapore
f
d
i
d
'
28
24
22
153
154
CHAO
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Pathology (1981), 13, January A I R TEMPERATURE N
N P
C N n
(OC)
s
N
m
W
N
x
0
I
X
z
FIG. 8 Temperatures at time and day of collapse compared with mean m o n t h l y temperatures
P W
4
ACUTE HEAT STROKE DEATHS
155
DISCUSSION Classically, the diagnosis of heat stroke rested upon (1) proven exposure to high environmental temperature, and the presence of (2) hyperpyrexia of over 41.1 "C, (3) hot, dry skin and (4) central nervous system signs.' However, subsequent investigations showed that these diagnostic yardsticks were inadequate. Heat stroke cases were found to occur under comparatively mild environmental conditions and in the early morning of relatively cool days. The duration of the physical exertion could be brief. Profuse sweating might occur and the recorded body temperature need not be above 41.1 "C.7These observations have been borne out by the present series. Eight of our cases occurred either in the morning or evening. The physical exertion was not exceptionally hard. The rectal temperature recorded was between 40°C to 42°C and all victims sweated profusely and had diarrhoea. Death in heat stroke cases has been reported as due to renal failure, hepatic failure, hyperkalaemia, cardiovascular collapse, haemorrhagic diathesis or a combination of these features. Damage to the kidney manifested itself as proteinuria, raised blood urea and acute renal failure. The renal lesions were thought to be at least partly due to direct thermal injury with coagulative necrosis of the tubular epithelium as the majority of the patients were not hypotensive or obviously dehydrated, and the raised blood urea level persisted in spite of intravenous therapy.8, The liver damage showed centrilobular degeneration and necrosis with dilatation of centrilobular sinusoids and central veins and cholestasis. Ultrastructural changes included degenerative changes or desquamation of sinusoidal cells, ballooning or flattening of microvilli, break in hepatocyte outer membranes and electron-lucent vacuoles along the sinusoidal border.". ' I In our cases, besides the centrizonal necrosis and cholestasis, there was fatty change ranging from mild to severe. This fatty change has not often been mentioned in other series. This could be due to (a) increased adipose fat breakdown by hyperpyrexia and (b) thermal damage to liver mitochondria resulting in inability t o mobilize Fat. Widespread coagulative necrosis was observed by us in the heart, liver, kidney and other organs. This manifested itself as clumping of the cytoplasmic protein as a result of hyperpyrexia. The cytoplasmic protein was simply cooked and coagulated. This phenomenon had been observed earlier in animal experiments.'* All the patients in this series died from disseminated intravascular coagulation, a s demonstrated by the clinical manifestation of bleeding diathesis and pathological changes of widespread microthrombus formation in various organs like brain, lungs, kidney, adrenals and pituitary gland. There were massive haemorrhages into the lungs, gastrointestinal tract, kidney, brain and other organs. The haemorrhages in heat stroke had been variously attributed to increased capillary permeability," hypoprothrombinaemia and thrombocytopenia,' increased fibrinolysis,' hypofibrinogenesis and excessive fibrinoly~is'~ and consumptive coagulopathy." The observation of widespread microthrombus formation supported the theory of DIC being due to endothelial damage which caused platelets to aggregate and triggered the clotting mechanism. Obstruction of small vessels led to infarcts and necrosis of the various organs. The damaged tissues released plasminogen activator and the resulting fibrinolysis reduced fibrinogen levels. The incoagulability of the blood contributed to further bleeding from the previously damaged tissues.* Analysis of the meteorological conditions at the time of collapse showed that in 7 of 10 cases the temperature exceeded the mean temperature for the month in which death occurred and similarly in 7 of 10 cases the maximum temperature during the day of collapse exceeded the average maximum temperature for the month. The time of collapse was recorded as
'
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Pathology ( I Y X I ) , 13, January
between 4.00 p.m. and 7.00 p.m. in 5 cases. Of these, 3 occurred when both the temperature at time ofcollapse and maximum temperature during the day exceeded the average mean and maximum respectively. In the remaining 2 cases the temperature at time ofcollapse exceeded the average mean temperature. One victim was a new recruit drafted 6 d earlier. One case occurred between 10.00 p.m. a n d 1 1.OO p.m. Though the day had been hot, the temperature a t the time ofcollapse was below the mean. This patient had a history of another collapse due to heat stroke one mth previously. Three cases occurred in the morning, in 2 instances the morning was hot. The remaining case occurred between 12 noon and 1.00 p.m. on a comparatively cool day; however the patient had been ill for the past 3 days. These observations support the fact that uncomfortable environmental conditions, previous illness, failure of acclimatization in the presence of physical exercise can lead to heat stroke. Attention to these factors in the training of new recruits could reduce its incidence. I t appears that the major factors leading to death are massive bleeding due to DIC and coagulative necrosis involving many major organs. Death is caused by multifactorial mechanisms.
ACKNOWLEDGEMENTS We thank the technicians of the Government and University Departments of Pathology for technical assistance, M r T. C. Tan for the photography, and Mrs T. H. K o h for typing the script. Addrc.s.s f h r c.orrc,sijond~,nc.r..T.C.C.. Department of Pathology, Ministry of Health, Singapore
References 1 . MAIAML!~. N.,H A Y M A K EW. R , & CUSIER, R. P. (1946): Heat stroke: a clinicopathological study o f 125 fatal cases. Milit. Surg. 99, 397-449.
2. SOHN R. S., SIJN,S. C., COIC‘OL.OUGH, H. L. u l . ( 196X): Heat stroke: an electron microscopic study
of endothelial ccll damage and disseminated intravasculnr coagulation. A r c h . Intern. Med. 122,
43 47.
3. G ~ o w h s ,G . H. A. J R & O’DONNLLL, T. F. J R (1974): Heat stroke-current concepts. N . EngI. J . Mid. 291, 564 566. T. F. J K (1975): Acute heat stroke4. O’DONNF.LI., epidcmiologic. biochemical, rcniil and coagulative 5ludies. J A M A 234, 824 828. 5. S I N N I A HR., , PWEL,H. S. & LIM, C. H. (1976): Glomerular lesions in asymptomatic microscopic haematuria discovered on routine medical examination. C’lin. N q h r o l . 5, 216-228. J . W. (1956): Observation 6. AIJSTIN, M. G. & BERRY, on onc hundred cases of hcat stroke. J A M A 161, 1525 1529.
7. ~~llI3OLF:T,S., COLL, R., GIL.AT, T. & SOHAR,E. (1967): Heat stroke: its clinical picture and mechanism in 36 cases. Q. J . Mcd.36, 525-548. 8. Ktw. M C., ARRAHAMS, C., LFVIN,M. W. ef a/. (1967): The effects of heat stroke on the function and structure of the kidney. Q. .I. Med. 36, 277 -300.
9. KNOCIIFL. .I.P., B H S ~ LW. , R.. HERNIXIN. E. G. iv d. (1961): The renal, cardiovascular, haemato-
logic and serum electrolyte abnormalities of hcat stroke. Am. .J. Mrd. 30, 299-309. , KENT.G. 10. KEW, M. C., BERSOIIN, I . , S E ~ T ~H.L & (1970): Liver damage in heat stroke. An?. J . M d 49, 192-202. 11. KEW, M. C., MINICK,0. T.. BAHU, R. M. c / ul. (1978): Ultrastructural changes in the liver in heat stroke. A m . J . Puthol. 90, 609-618. L. V. (1954): Heat death. S I .An?. 12. HEILBRUNN, 190, 4-70. 13. WRIGHT,D. O., REPPERT,L. B. 8r CUTTINO, J. (1946): Purpuric manifestation of heat stroke: studies of prothrombin and platelets in twelve cases. Arch. Intern. Med. 77, 27-36. J. R. (1967): 14. MEIKLE,A. W. & GKAYHILL, Fibrinolysis and hemorrhage in a fatal case of heat stroke. N . Engl. J . Med. 276, 911-913. 15. WERER,M. B. & BLAKELY, J. A . (1969): The haemorrhagic diathesis of heat stroke: a consumptive coagulopathy successfully treated with Heparin. Luncer i, I 1 90-1 192.