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Extremes of Temperature: Hypothermia
Extremes of Temperature: Hypothermia FM Bright and RW Byard, The University of Adelaide, Adelaide, SA, Australia r 2016 Elsevier Ltd. All rights reserved.
Abstract The most common cause of lethal hypothermia is accidental exposure to low environmental temperatures, contributed to by inadequate or wet clothing, and damp or windy conditions. Other exacerbating factors include low muscle mass, alcohol and drug ingestion, trauma, open injuries, immobility, and certain underlying illnesses. Those at the extremes of age are at highest risk. Typical findings at autopsy include superficial gastric lesions, so-called Wischnewski spots, pink discoloration of the skin over the large joints, acute pancreatic inflammation with fat necrosis, fatty change in cells of the heart, liver and kidneys, skeletal muscle hemorrhage, and vacuolization of renal tubular cells.
Introduction Hypothermia occurs when the core temperature of the body falls below 35 1C. It is characterized by subtle morphological findings with complex underlying pathology and is a recognized, although probably underestimated, cause of death in man (Turk, 2010; Mallet, 2002; Dettmeyer, 2011). As humans are homeothermic organisms there is a need to constantly maintain a stable core body temperature despite changes in the surrounding environment (Reuler, 1978; Madea et al., 2008). Deviation in core body temperature below normal levels will have significant effects on thermoregulatory control and metabolic processes (Reuler, 1978; Bristow, 1984), with a greater than 70% mortality when the core temperature drops to 30 1C, and 90% at 26 1C (Zhou and Byard, 2011). Hypothermia can be graded as mild (o35 1C), moderate (35–32 1C), or severe (o32 1C). The most common cause of lethal hypothermia is accidental exposure to low environmental temperatures exacerbated by a number factors such as inadequate or wet clothing, damp conditions, wind, low muscle mass, alcohol ingestion and alcoholism, certain drugs, trauma, open injuries, immobility, cardiovascular, neurological, and endocrine disorders, and psychiatric illness. Individuals at the extremes of age are at highest risk (Matz, 1972; Zhou and Byard, 2011).
Problems in Diagnosis In forensic pathology, the diagnosis of fatal hypothermia may be problematic due to the subtlety of morphological features, nonspecific findings at autopsy, variability and difference in the frequency of diagnostic findings, and the possibility of suspicious circumstances due to aberrant behavior prior to death (Wedin et al., 1979; Rothschild and Schneider, 1995; Figure 1). As it is not usual to have the core temperature of a decedent at the time of death the diagnosis of lethal hypothermia, therefore, relies upon assessing the circumstances of the death (including the ambient temperature) and the exclusion of other factors (Preuß et al., 2004; Madea et al., 2008).
Subtle morphological features
Nonspecific findings at autopsy
Pathophysiology When the human body is exposed to decreased environmental temperatures the hypothalamus activates and initiates several counter-regulatory mechanisms such as vasoconstriction and chemical thermogenesis. (Caroselli et al., 2009; Nirula and Gentilello, 2005; Lonning et al., 1986). However, as the temperature declines further, heat loss exceeds heat production and thermoregulatory mechanisms begin to fail (Turk, 2010;
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Emslie-Smith, 1958). Lethal mechanisms include ventricular fibrillation or asystole, contributed to by myocardial ischemia, hypoxia, electrolyte abnormalities, and elevated catecholamine levels (Zhou and Byard, 2011).
Hypothermia
Possible high variability/ frequency of diagnostic findings
Suspected suspicious circumstances
Figure 1 Problems that occur with the diagnosis of hypothermia.
Encyclopedia of Forensic and Legal Medicine, Volume 2
doi:10.1016/B978-0-12-800034-2.00174-9
Extremes of Temperature: Hypothermia
Difficulties may arise from unusual behavior associated with falling core temperatures, such as paradoxical undressing due to thermoregulatory failure where a person may be found semi-naked lying in snow with a trail of clothing left behind them. Similarly the ‘hide and die’ syndrome may occur in confused elderly recluses who are found hidden, for example, in a laundry under a pile of newspapers (Prahlow and Byard, 2012). Problems in assessment in the latter situation may be further compounded if the decedent suffered from Diogenes, or so-called senile squalor, syndrome where elderly socially isolated individuals live in domestic squalor with self neglect and hoarding (Bright et al., 2013a; Byard and Tsokos, 2007; Byard, 2014).
Morphological Features of Fatal Hypothermia Unfortunately the morphological features of hypothermia are neither specific nor diagnostic (Tables 1 and 2) and variability in the frequency of these changes further complicates the assessment of deaths (Wolf et al., 1999; Turk, 2010). Typical findings include pink discoloration of the skin over the extensor surfaces of large joints, such as the elbows, knees, and hips (Figure 2), acute pancreatic inflammation with fat necrosis, fatty change in cells of the heart, liver and kidneys, skeletal muscle hemorrhage, vacuolization of renal tubular cells, and probably the most significant finding, that of superficial gastric lesions, that have been called Wischnewski spots (Bright et al., 2013a). Frost bite may be observed in individuals who have survived for some time at temperatures below 0 1C due to tissue damage from freezing with peripheral circulatory failure.
Wischnewski Spots In 1895, Wischnewski observed multiple dark to black superficial hemorrhagic lesions of the gastric mucosa in deaths due to hypothermia (Figure 3). A contemporary translation of his original paper states: Table 1
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On the mucous membrane of the stomach in humans who have died exclusively from the effects of low temperatures, 5 to 100 hemorrhages are invariably present. Their size ranges from 0.5 to 1.0 cm. They have a round to oval form. Sometimes they are punctiform and lie about 1 to 2 in. apart. These hemorrhages are raised slightly above the surface of the mucous membrane, can be very easily scrapped (sic) away and leave behind nothing conspicuous on the gastric mucosa. (Wischnewski, 1895; Ehlrich, 2004)
Although not considered pathognomonic of hypothermia, Wischnewski spots have been accepted as the most reliable indicator of significantly reduced core temperature (Birchmeyer and Mitchell, 1989; Sperhake et al., 2004; Turk, 2010; Madea et al., 2008; Dettmeyer, 2011). Wischnewski spots vary in frequency, being found in 40–91% of cases in different series (Table 3; Dettmeyer, 2011; Madea et al., 2008). While Wischnewski reported a high incidence of 91% (Wischnewski, 1895), Hirvonen (1976) observed them in only half of the studied cases, describing them as scarce and irregular. Variation in frequency of Wischnewski spots may depend on circumstances of death, duration of exposure to cold stimulus, an individual’s reaction to cold stress and the resistance of the gastric mucosa to significantly decreased temperatures (Hirvonen, 1976; Madea et al., 2008; Wolf et al., 1999). Although Wilschnewski described raised hemorrhagic areas that could be easily removed from the mucosa, they were later considered to be ulcers or erosions. In an immunohistochemical study by Tsokos et al. (2006), however, it was proposed that the lesions resulted from the action of gastric acid on hemoglobin in areas of interstitial mucosal hemorrhage, and not from ulceration. Conversely, Hirvonen and Elfving (1974) reported that the erosions extended ‘halfway through the mucosa’ and that hemorrhage was ‘not always present.’ It appears most likely to the authors that lesions of different ages and/or severity may have different appearances and that erosions or ulcers may result from loss of friable and necrotic material arising from hemorrhage within the superficial layers of the gastric mucosa Figure 4.
Summary of the main external morphological features of hypothermia
External feature
Description
Pathophysiology
Frequency
Specificity
Blistering of skin Frost erythema
Local blistering Pinkish, purple discoloration of skin over large extensor joints (elbow, knee, and hip), sometimes projecting areas (ears, nose, and male genitalia)
Unknown Variable: 54–75%
Nonspecific Nonspecific
Hematomas/abrasions
Cutaneous lesions, reddening abrasions on elbows, and knees
Exposure to cold damages tissue Unclear; – Pronounced vascular hyperemia in subepidermal soft tissue – Capillary damage – Damaged erythrocytes – Plasma/ hemoglobin leakage into tissues Terminal burrowing behavior prior to death
Variable: depends on circumstances of death
Nonspecific
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Table 2
Extremes of Temperature: Hypothermia
Summary of the main internal morphological features of hypothermia
Internal feature
Description
Pathophysiology
Frequency
Specificity
Bright red blood and lividity
Blood appears bright red
Left shifting of oxygen-hemoglobindissociatian curve
Nonspecific
Hemorrhaging into core muscles
Specifically the illiopsoas muscle
Case dependent decreased diagnostic value as these changes can occur postmortem Rare finding
Wischnewski ulcers
– Superficial hemorrhagic dark blackish brown ‘leopard skin’ lesions of gastric mucosa – Necrosis with hematin formation – Characteristic linear pattern
Pancreatic changes
Fatty changes
Vacuolisation cells
Acute/hemorrhagic pancreatitis. Patches of fat necrosis on organ surface, raised serum amylase levels, focal/ diffuse infiltration of leukocytes, inflammation, vacuolisation of adenoid cells Heart liver and kidneys
Liver, pancreas, renal, and adrenal cells
Unclear;
– Hypoxic damage – Diapedesis – Insufficient circulation due to hypothermia-induced vasoconstriction – Misbalance of decreased perfusion and oxygen requirement Unclear; – Autolysis – Erythrocytes destroyed – Hemoglobin release – Disturbances of microcirculation – Involvement of tissue amines – Ischemic reperfusion – Increased capillary permeability and mucosal congestion Unclear; – Thrombosis in microcirculation that results in ischemia and perilobular necrosis – Vacuolisation due to impaired exocytosis and permeability
Unclear; possibly a result of energy depletion due to post shockinduced hypoxia – Tubular reabsorption following increased mobilization of triglycerides Loss of glycogen
Figure 2 Pink discoloration over both knees in a case of lethal hypothermia.
Nonspecific
40–100% cases dependent on exposure, resistance to cold and the individual
Nonspecific, however, most reliable feature of significantly reduced temperatures
Variable 20–30%
Nonspecific
Variable; case dependent
Nonspecific
Rare-variable
Nonspecific
Figure 3 Wischnewski spots in the gastric mucosa in a case of fatal hypothermia producing a typical ‘leopard skin’ effect.
Extremes of Temperature: Hypothermia
The exact etiology of these lesions remains unclear, however, their pathogenesis has been attributed to disturbances in microcirculation, involvement of tissue amines, breakdown of hemoglobin and ischemic-reperfusion injury (Madea et al., 2008; Tsokos et al., 2006; Wolf et al., 1999; Hirvonen and Elfving, 1974; Sperhake Table 3 Frequency of Wischnewski spots in cases of fatal hypothermia Frequency (%)
Sample
References
91.3 91 88 86 79 64 60 B50 44 40
23 44 25 43 24 67 15 22 23 30
Thrun (1992) Wischnewski (1895) Gillner and Waltz (1971) Mant (1969) Lim and Duflou (2008) Nikolic et al. (2010) Birchmeyer and Mitchell (1989) Hirvonen (1976) Mizukami et al. (1999) Kinzinger et al. (1995)
Age-related vulnerability Elderly, infants and young children Environment Temperature
Drugs and alcohol Hypothermic death
Underlying medical conditions
Social factors Diogenes syndrome Place of discovery Indoors vs outdoors
Figure 4 Various demographic and epidemiologic parameters associated with death due to hypothermia.
Table 4
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et al., 2004; Table 3). While stress may also be involved in the pathogenesis of Wischnewski spots, it is unclear if the gastric lesions develop due to stress caused by hypothermia or as a direct result of significantly reduced core body temperature (Takada et al., 1991; Birchmeyer et al., 1989; Wolf et al., 1999). A number of rodent models have been developed to test this possible association, with reports that stress, in conjunction with the integrity of higher order processing systems plays an important role in their development (Table 4). For example, Vincent et al. (1984) reported that aggressive behavior and an ability to decrease stress with access to a biting mechanism during cold exposure, had a protective effect by counteracting the effects of hypothermia, as rats showed fewer and smaller gastric lesions. The authors have recently developed an animal model which failed to generate Wischnewski spots in rats that were taken from a relatively low stress environment and exposed to decreased temperatures for a number of hours (Bright et al., 2013b). The absence of Wischnewski spots in animals that had died of hypothermia provides further support for stress being an important cofactor in the development of these lesions. The absence of renal vacuoles could also be explained by a similar mechanism (Zhou et al., 2014).
Pancreatic Changes A wide range of pancreatic changes in deaths due to hypothermia have been described that vary in both frequency and type (Table 5). While acute pancreatitis has been identified in hypothermic adults (Foulis, 1982; Mant, 1969; Symbas et al., 1961; Read et al., 1961), there are many contradictory findings between studies, with reports that hemorrhage and inflammatory changes of the pancreas are not reliable indicators of these deaths (Stiff et al., 2003; Preuß et al., 2006). The possibility of other causal factors in the pathogenesis of acute pancreatitis such as alcohol abuse, gall stones, trauma, and shock also means that it is unclear whether pancreatic changes are a primary or a secondary event (Foulis, 1982; Preuß et al., 2007).
Animal models of hypothermia involving stress
Animal (rat) models of hypothermia
References
Histamine and serotonin in the gastric erosions of rats dead from exposure to cold: a histochemical and quantitative study Role of hypothermia in the production of gastric ulcers in a rat spinal cord transection model Aggression, body temperature and stress ulcer Age-related differences in response to acute cold challenge ( 10 1C) in male F344 rats
Hirvonen and Elfving (1974)
Analysis of the cold water restraint procedure in gastric ulceration and body temperature Hydrogen sulphide-induced hypothermic attenuates stress-related ulceration in rats
Sigman and Gillich (1981) Vincent et al. (1984) Kiang-Ulrich and Hovarth (1985) Landeira-Fernandez (2004) Lou et al. (2008)
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Table 5
Extremes of Temperature: Hypothermia
Frequency and type of pancreatic changes in cases of fatal hypothermia
Frequency (%)
Type of change
Sample
References
73 67 63 38 25 18
Raised serum amylase levels Focal necrosis of adipose tissue and hemorrhagic pancreatitis Necrosis of the pancreas Hemorrhagic pancreatitis, focal pancreatitis with necrosis of adipose tissue Marked congestion and interstitial hemorrhage Macroscopically visible pancreatic hemorrhages, nonhemorrhagic, and hemorrhagic pancreatitis Focal and diffuse pancreatitis (post therapeutic hypothermia)
15 43 8 13 8 22
Duguid et al. (1961) Mant (1969) Foulis (1982) Duguid et al. (1961) Foulis (1982) Hirvonen (1976)
50
Sano and Smith (1940)
10
While Mant described hemorrhagic pancreatitis in 67% of fatal hypothermic cases (Mant, 1969), Preuß et al. (2007) showed macroscopic hemorrhage of the pancreas without acute inflammation in only 4% of cases. The difference in frequency and type of pancreatic changes between investigations may, however, be due to variations in sample size and methodology. For example, while Preuß et al. had a large sample of 143 cases, retrospective review may have resulted in underreporting. The review of Mant’s 49 cases may have also been skewed by an overrepresentation of the elderly with the possibility of preexisting pancreatic diseases (Mant, 1969; Preuß et al., 2007). Three possible mechanisms were proposed by Foulis in 1982 for the relationship between acute pancreatitis and hypothermia that involved:
• • •
Ischemic pancreatitis, from the microcirculatory shock of hypothermia Hypothermia and acute pancreatitis, secondary to alcohol abuse Severe pancreatitis as primary disease with hypothermia resulting from social circumstances (Foulis, 1982).
Epidemiology Numerous epidemiological studies of the morbidity and mortality of hypothermia have retrospectively reviewed data on hypothermic cases from hospital admissions, autopsy records, coronial reports and national mortality statistics (Table 6). These have recognized that exposure to significantly decreased temperatures is not the only factor in these deaths (Thomas, 1988; Herity et al., 1991; Lim and Duflou, 2008; Danzl et al., 1987; McKee, 1989, 1990).
Age-Related Vulnerability The extremes of age are associated with increased morbidity and mortality associated with hypothermia (Taylor et al., 2001; Glickman et al., 2002; Megarbane
et al., 2000; Herity et al., 1991; Reuler, 1978; Wagner and Horvath, 1985; Altus et al., 1980; Collins et al., 1977; Thomas, 1988; Elbaz et al., 2008; Sloan and Keatinge, 1973). Infants and young children have an increased risk due to their lack of muscle mass and adiposity and their increased surface area to body mass ratio (Sloan and Keatinge, 1973; Turk, 2010). There are, however, relatively few studies into hypothermic deaths in children. The elderly also are more susceptible to the effects of hypothermia due to failing biological mechanisms of temperature regulation, such as vasoconstriction and shivering, not being sufficient to maintain the balanced relationship between heat loss and heat production. The elderly are also less able to discern cold temperatures due to possible autonomic nervous system dysfunction and may not dress appropriately, thus increasing body heat loss. Elderly recluses often do not use heating in an attempt to be ‘thrifty,’ particularly in the face of rising electricity and oil prices (Bright et al., 2013a; Thomas, 1988; Herity et al., 1991; Megarbane et al., 2000; Taylor et al., 2001; Elbaz et al., 2008; Dharmarajan and Widjaja, 2007; Krag and Kountz, 1950; Watts, 1971). Kiang-Ulrich and Hovarth (1985) using an animal model also showed that responses to acute cold exposure deteriorate with age (Table 4). Thomas et al. in a 10-year review of hospital discharge codings and mortality rates showed that elderly individuals were disproportionately represented, accounting for 65% of hypothermic deaths. The higher incidence of deaths in the elderly was attributed to abnormal temperature perception and regulation, intercurrent illnesses, social isolation, and inadequate housing or poverty (Thomas, 1988). Collins et al. concluded that both physiologic and behavioral factors involved in poor temperature discrimination, age-related decline in efficiency of cold-defence mechanisms and a lack of adjustment of the thermal environment all contribute to the increased vulnerability and susceptibility of the elderly cohort (Collins et al., 1981, 1977; Collins, 1986). A caveat in the assessment of age-related variables associated with hypothermia relates to differences in sample sizes and methods of evaluation (Table 6); for example, studies of healthy retired individuals with no
Table 6
Retrospective reviews of the morbidity and mortality of hypothermia in varying populations
Author/Year
Period
Location
Method
Sample
Key findings
Altus et al. (1980)
5 years
Tampa, FL, USA
Case reports from hospital admissions
4 case reports
– Predicted that hypothermia will become
Discharge codings of preceding 10 years at University of Mississippi Medical Center Reviewed for hypothermia, abnormal temperature, or environment related illness
35 patients with hypothermia diagnosis
more prevalent in warmer climates in the future – Inadequacy of insulation of homes for cold temperatures Extreme environmental conditions not only factor required to produce hypothermia; other factors involved Indoors 71% cases Outdoors 29% cases Male 75%
Thomas (1988)
10 years (1968–1980)
Jackson, MI, USA
34 patients able to be reviewed 24 primary hypothermia 10 secondary hypothermia
5 years (1933–1988)
Onondaga County, NY, USA
County Medical Examiner's office
16 deaths 15 autopsies
Tanaka and Tokudome (1990)
1974–1933
Tokyo, Japan
Autopsy records/reports from Medical Examiner's office
157 deaths
Herity et al. (1991)
1979–1985
Republic of Ireland
Survey of deaths and hospital admissions due to hypothermia identified from death certificates and Hospital in patient data
453 deaths recorded
Megarbane et al. (2000)
17 years (1931–1998)
Paris, France
Retrospective clinical investigation in a medical ICU
81 patients
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Death 37% 65% Elderly Single most precipitating factor; ingestion of alcohol 33% cases – 9 cases definitive petechial/ulcerative changes in gastric mucosa – Pattern of ulceration is as important as the presence of Wischnewski ulcers – Suggested protective effects of alochol – Male predominance (143 M, 14 F) – 77% Outdoor cases, 23% Indoors – Majority attributed to alcoholism (few cases showed no evidence of alcoholism) – Age: 40–50 years 60% cases – Incidence in Male vs. Female was similar – Males had a 30% increased fatality – Hypothermia statistics must be interpreted cautiously – Incidence and Mortality increased with age – Outdoors 21% cases – Indoors 79% cases – 36% died – Patients found indoors more severely affected and greater mortality rate – Age predictive factor of death (Continued )
Extremes of Temperature: Hypothermia
Birchmeyer and Mitchell (1989)
Black 71%
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Table 6
Continued
Author/Year
Period
Location
Method
Sample
Key findings
underlying cause of hypothermia Roeggla et al. (2001)
1991–1998
Vienna, Italy
Retrospective cohort study of patients admitted to ED
80 patients
Taylor et al. (2001)
1983–1999
Jefferson County, AL, USA
Autopsy reports coronial investigations
63 cases
Elbaz et al. (2008)
6 years (1999–2005)
Beer Sheva, Southern Israel
Retrospective study: Soroka University Medical Center
169 patients
Admissions to hospital with diagnosis of hypothermia
Lim and Duflou (2008)
5 years (2001–2005)
Sydney, Australia
Electronic Autopsy records
95 cases 24 fatal hypothermia
– 34% mortality rate – Hypothesized that predisposing conditions in urban settings may aggravate hypothermia and the damage it induces – Psychological problems are major contributing factor – Majority of patients had complex medical history – Indoor hypothermia is a special type of hypothermia – Increased rate among blacks and males 80 years þ – Two main groups affected elderly and middle-aged males – Chronic mental conditions 90% cases – Criteria for assigning hypothermia as cause of death may not be uniform among jurisdictions; comparison is, therefore, difficult – Hospital mortality rate 47.3% – Indoor hypothermia associated with a worse outcome – Risk of hypothermia present in warmer months also, not limited to cold climates – Majority of patients had major medical conditions contributing to presence and severity of hypothermia – Greater incidence in individuals 75 years þ – Female predominance 63% – Deaths occurred in all seasons – Gastric Wischnewski erosions 79% cases – Paradoxical undressing 29% cases – All cases had significant preexisting natural disease process – Elderly most affected average age: 76 years
Extremes of Temperature: Hypothermia
– Suggested that associated illness is primary
Extremes of Temperature: Hypothermia
medical conditions may not be representative of the general population (Schellan et al., 2010).
Underlying Disorders Associated with Hypothermia A wide range of natural diseases have been identified as predisposing factors to death from hypothermia (Turk, 2010; Megarbane et al., 2000; McKee, 1990; Taylor et al., 2001; Table 6). These diseases are mostly agerelated (Elbaz et al., 2008; Lim and Duflou, 2008; Megarbane et al., 2000; Roeggla et al., 2001; Thomas, 1988). Conditions contributing to hypothermia include hypothyroidism; diabetes mellitus; trauma; sepsis; stroke; and renal, heart, and liver failure (Maclean et al., 1973; Elbaz et al., 2008; Megarbane et al., 2000; Roeggla et al., 2001). It is felt that these conditions interfere with thermoregulation, predispose to abnormal temperature control and regulation and have the potential to aggravate and enhance tissue damage induced by hypothermia (Roeggla et al., 2001). An additional problem in the forensic evaluation of cases is that these conditions may mask the mechanism of death (Lim and Duflou, 2008; Elbaz et al., 2008). Mental illnesses such as schizophrenia, bipolar disorder, Alzheimer’s disease, and dementia have also been identified as potential risk factors for hypothermic deaths (Taylor et al., 2001; Lim and Duflou, 2008). Alcohol intoxication is a well known factor in certain hypothermic fatalities for a variety of reasons, occurring in up to 64% of cases in some series (Tanaka and Tokudome, 1990). Alcohol promotes heat loss via the dilation of superficial blood vessels and may render individuals incapable of removing themselves from a cold environment (Taylor et al., 2001; Kalant and Le, 1984). Interestingly, it has been suggested that alcohol may reduce the incidence of Wilschnewski spots by reducing physiologic stress (Birchmeyer and Mitchell, 1989). The most frequent location of hypothermic deaths associated with alcohol has been outdoors with 40- to 50-year-old males being most susceptible (Tanaka and Tokudome, 1990; Taylor et al., 2001).
Sex and Racial Differences Differences in percentages of males and females in various studies may be attributed to a variety of causes. For example, a male predominance occurring in outdoor deaths may be related to specific activities such as skiing and to intoxication. Tanaka and Tokudome (1990) reported a 91% incidence of hypothermic deaths in males, compared to Lim and Duflou who reported a female predominance of 63% (Lim and Duflou, 2008). Sex differences in incidence may relate to variations in adiposity, muscle mass and metabolic responses between
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males and females (Anderson et al., 1995; Keatinge, 1960; Budd and Warhaft, 1966; Wagner and Horvath, 1985). The frailty syndrome occurs in the elderly who have reduced ambulation and significant loss of skeletal muscle bulk with lowering of the body mass index. Given that lighter bodies lose heat more rapidly than heavier bodies this may also be a predisposing factor to lethal hypothermia that would contribute to the higher numbers of female deaths indoors. Although black individuals have been identified in some studies as being more susceptible to hypothermia and its effects, other studies have found no significant influence of race on thermosensitivity (Turk et al., 2005, 2006; Thomas, 1988; Taylor et al., 2001; Farnell et al., 2008).
Location of Deaths Deaths from hypothermia indoors are well documented (Roeggla et al., 2001; Megarbane et al., 2000; Tanaka and Tokudome, 1990; Elbaz et al., 2008). It has been suggested that victims found indoors may experience longer exposure to the cold and have a lowered cooling rate, whereas outdoor victims, although exposed to lower temperatures, may experience a shorter cooling time (Roeggla et al., 2001). Megarbane et al. reported 79% of hypothermic deaths occurring indoors, describing victims as generally older with underlying disorders that led to a higher risk of mortality compared to subjects found outdoors (Megarbane et al., 2000; Elbaz et al., 2008). This was the finding in studies in South Australia that found inadequate heating and insulation, individual vulnerability, lack of awareness of hazards associated with hypothermia, and a lack of preparation for cold weather, all contributed to fatal outcomes (Bright et al., 2012, 2013a). The colder months of the year are known to be associated with an increase in death rates usually associated with cardiovascular and respiratory illnesses in the elderly. This has ranged from 5% to 30% and has been termed the excess winter mortality. Although hypothermic deaths contribute to this they are not limited to colder climates, with a recent study showing slightly higher death rates from hypothermia in South Australia (3.9/ 100 000) and Sweden (3.3/100 000), despite the obvious differences in external temperatures (average temperature in South Australia¼20 1C, and in Sweden¼10 1C) (Bright et al., 2014). A previous review in Sydney, Australia, also highlighted the significance of fatal hypothermia as a public health problem in warmer climates (Lim and Duflou, 2008). Similarly Elbaz et al. (2008) investigated the severity and mortality of hypothermia in the desert climate of Southern Israel, concluding that hypothermia should not be overlooked in regions with temperate climates, as the risk of hypothermia was present even during the warmest months of the year.
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Extremes of Temperature: Hypothermia
Conclusions It is clear that hypothermia has a complex pathophysiology with numerous parameters that contribute to the associated morbidity and mortality. The diagnosis at postmortem may be very difficult and may be missed unless adequate death scene information is available. The sensitivity, specificity and etiology of the typical morphologic changes are, however, incompletely understood.
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Foulis, A.K., 1982. Morphological study of the relationship between accidental hypothermia and acute pancreatitis. Journal of Clinical Pathology 35, 1244–1248. Gillner, E., Waltz, H., 1971. Zur Symptomatik des Erfrierens. Kriminal Forens Wiss 5, 179–185. Glickman, E.L., Caine-Bish, N., Cheatham, C.C., Blegen, M., Ptkanowicz, E.S., 2002. The influence of age on thermosensitivity during cold water immersion. Wilderness and Environmental Medicine 13, 194–202. Herity, B., Daly, L., Bourke, G.J., Horgan, J.M., 1991. Hypothermia and mortality and morbidity. An epideiological analysis. Journal of Epidemiology and Community Health 45, 19–23. Hirvonen, J., 1976. Necropsy findings in fatal hypothermia cases. Forensic Science 8, 155–164. Hirvonen, J., Elfving, R., 1974. "Histamine and Serotonin in the gastric erosions of rats dead from exposure to cold: A histochemical and quantitative study" Zeitschrift für Rechtsmedizin. Journal of Legal Medicine 74, 273–281. Kalant, H., Le, A.D., 1984. Effects of ethanol on thermoregulation. Pharmacology & Therapeutics 23, 313–364. Keatinge, W.R., 1960. The effects of subcutaneous fat and of previous exposure to cold on the body temperature, peripheral blood flow and metabolic rate of men in cold water. Journal of Physiology 153, 166–178. Kiang-Ulrich, M, Horvath, S., 1985. Age-related differences in response to acute cold challenge ( 10 1C) in male F344 rats. Experimental Gerontology 20, 201–209. Kinzinger, R., Rissie, M., Puschel, K., 1995. ‘‘Kä lteidiotie’’: Paradoxes Entkleiden bei Unterkü hlung. Archiv für Kriminologie 187, 47–56. Krag, C.L., Kountz, W.B., 1950. Stability of body function in the aged I. Effect of exposure to cold. Journal of Gerontology 5, 227–235. Landeira-Fernandez, J., 2004. Analysis of the cold-water restraint procedure in gastric ulceration and ody temperature. Physiology and Behavior 82, 827–833. Lim, C., Duflou, J., 2008. Hypothermia fatalaties in a temperate climate: Sydney, Australia. Pathology 41 (1), 46–51. Lonning, P.E., Skullberg, A., Abyholm, F., 1986. Accidental hypothermia: Review of the literature. Acta Anaesthesiologica Scandinavica 30, 601–613. Lou, L.X., Geng, B., Du, J.B., Tang, C.S., 2008. Hydrogen sulphide-induced hypothermia attenuates stress-related ulceration in rats. Clinical and Experimental Pharmacology and Physiology 35, 223–228. Maclean, D., Murison, J., Griffiths, P.D., 1973. Acute pancreatitis and diabetic ketoacidosis in accidental hypothermia and hypothermic myxoedema. British Medical Journal 4, 757–761. Madea, B., Tsokos, M., Preuß, J., 2008. Morphological findings, their pathogenesis and diagnostic value. Forensic Pathology Reviews 5, 3–21. Mallet, M.L., 2002. Pathophysiology of accidental hypothermia. Oxford Journal of Medicine 95, 775–785. Mant, A.K., 1969. Autopsy diagnosis of accidental hypothermia. Journal of Forensic Science 16, 126–129. Matz, R., 1972. Hypothermia in diabetic acidosis. Hormones 3, 36–41. McKee, C.M., 1989. Deaths in winter: Can Britain learn from Europe? European Journal of Epidemiology 5 (2), 178–182. McKee, C.M., 1990. Deaths in winter in Northrn Ireland: The role of low temperature. Ulster Medical Journal 59 (1), 17–22. Megarbane, B., Axler, O., Chary, I., Pompier, R., Brivet, F.G., 2000. Hypothermia with indoor occurrence is associated with a worse outcome. Journal of Intensive Care Medicine 26, 1843–1849. Mizukami, H., Shimizu, K., Shiono, H., Uezono, T., Sasaki, M., 1999. Forensic diagnosis of death from cold. Legal Medicine 1, 204–209. Nikolic, S., Zivkovic, M., Zivkovic, V., Jukovic, F., 2010. Hypothermia as the cause of death in forensic pathology: Autopsy study. Srpski arhiv za celokupno lekarstvo 138 (7−8), 467–472. Nirula, R., Gentilello, L., 2005. Detrimental effects of hypothermia. In: Tisherman, S. A., Sterz, F. (Eds), Therapeutic Hypothermia. New York, NY: Springer. Molecular and Cellular Biology of Critical Care Medicine 4, 235−249. Prahlow, J.A., Byard, R.W., 2012. Hypothermia. Atlas of Forensic Pathology. New York, NY: Springer, pp. 743−752 (Chapter 18). Preuß, J., Lignitz, E., Dettmeyer, R., Madea, B., 2004. Fatty degeneration in renal tubule epithelium in accidental hypothermia victims. Forensic Science International 141, 131–135. Preuß, J., Lignitz, E., Dettmeyer, R., Madea, B., 2006. Pancreatic changes in cases of death due to hypothermia. Forensic Science International 159, 194–198. Preuß, J., Thierauf, A., Dettmeyer, R., Madea, B., 2007. Wischnewsky's spots in an ectopic stomach. Forensic Science International 169, 220–222.
Extremes of Temperature: Hypothermia
Read, A.E., Emslie-Smith, D., Gough, K.R., Holmes, R., 1961. Pancreatitis and accidental hypothermia. Lancet 2 (7214), 1219–1221. Reuler, J.B., 1978. Hypothermia: Pathophysiology, clinical settings and management. Annals of Internal Medicine 89, 519–527. Roeggla, M., Holzer, M., Roeggla, G., et al., 2001. Prognosis of accidental hypothermia in the urban setting. Journal of Intensive Care Medicine 16, 142–149. Rothschild, M.A., Schneider, V., 1995. “Terminal burrowing behavior” − A phenomenon of lethal hypothermia. International Journal of Legal Medicine 107, 250–256. Sano, M.E., Smith, C., 1940. Fifty post-mortem patients with cancer subjected to local or generalized refrigeration. Journal of Laboratory and Clinical Medicine 26, 443. Schellan, L., van Marken Lichtenbelt, W.D., Loomans, M.G.L.C., Toftum, J., de Wit, M.H., 2010. Differences between young adults and elderly in thermal comfort, productivity and thermal physiology in response to a moderate temperature drift and a steady-state condition. Indoor Air 20, 273–283. Sigman, H.H., Gillich, A., 1981. Role of hypothermia in the production of gastric ulcers in a rat spinal cord transection model. Digestive Diseases and Sciences 26 (1), 60–64. Sloan, R.E.G., Keatinge, W., 1973. Cooling rates of young people swimming in cold water. Journal of Applied Physiology 35, 371–375. Sperhake, H.P., Rothschild, M., Risse, M., Tsokos, M., 2004. Histomorphology of Wischnewsky spots: Contribution to the forensic histopatology of fatal hypothermia. In: Oehmichen, M. (Ed.), Hypothermia. Clinical, Pathomorphological and Forensic Features. Lubek: Schmidt-Romhild, pp. 211–220. Stiff, R.E., Morris Stiff, G., Torkington, J., 2003. Hypothermia and acute pancreatitis: Myth or reality? Journal of the Royal Society of Medicine 96, 228–229. Symbas, P.N., Byrd, B.F., Johnson, J.S., Younger, R., Foster, J.H., 1961. Influence of hypothermia on pancreatic function. Annals of Surgery 154 (4), 509–515. Takada, M., Kusano, I., Yamamoto, H., et al., 1991. Wischnewsky's gastric lesions in accidental hypothermia. American Journal of Forensic Medicine and Pathology 12, 300–305. Tanaka, M., Tokudome, S., 1990. Accidental hypothermia and death from cold in urban areas. International Journal of Biometereology 34, 242–246.
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Taylor, A.J., McGwin, G., Davis, G.G., et al., 2001. Hypothermia deaths in Jefferson County, Alabama. Injury Prevention 7, 141–145. Thomas, D.R., 1988. Accidental hypothermia in the sunbelt. Journal of General Medicine 3, 552–554. Thrun, C., 1992. Verfettung der Tubulusepithelien der Niere − ein Hinweis für Hypothermie? Rechtsmedizin 2, 55–58. Tsokos, M., Rothschild, M., Madea, B., Risse, M., Sperhake, J.P., 2006. Histological and immunohostochemical study of Wischnewsky spots in fatal hypothermia. American Journal of Forensic Medicine and Pathology 27, 70–74. Turk, E.E., 2010. Hypothermia. Forensic Science, Medicine and Pathology 6, 106–115. Turk, E.E., Sperhake, J.P., Madea, B., Preub, J., Tsokos, M., 2006. Immunohistochemical detection of hemoglobin in frost erythema. Forensic Science International 158, 131–134. Turk, E.E., Sperhake, J.P., Pueshel, K., Tsokos, M., 2005. An approach to the evaluation of fatal hypothermia. Forensic Science 1, 31–36. Vincent, G.P., Pare, W.P., Prenatt, J.E.D., 1984. Aggression, body temperature ans stress ulcer. Physiology and Behavior 32, 265–268. Wagner, J.A., Horvath, S., 1985. Influence of age and gender on human thermoregulatory responses to cold exposures. Journal of the American Physiological Society 85, 180–186. Watts, A.J., 1971. Hypothermia in the aged: A study of the role of cold-sensitivity. Environmental Research 5, 119–126. Wedin, B., Vanggaard, L., Hirvonen, J., 1979. Paradoxial undressing in fatal hypothermia. Journal of Forensic Science 24, 543–553. Wischnewski, S.M., 1895. Ein neues Kennzeichen des Todes durch Erfrieren. Bote f gerichtl Med 3, 11–20. Wolf, D.A., Aronson, J., Rajaraman, S., Veasey, S.P., 1999. Wischnewski ulcers and acute pancreatitis in two hospitalized patients with cirrhosis, portal vein thrombosis and hypothermia. Journal of Forensic Science 44 (5), 1082–1085. Zhou, C., Bright, F., Winskog, C., Yool, A., Byard, R.W., 2014. Lethal hypothermia in an animal model not associated with basal renal epithelial vacuolization. Journal of Forensic and Legal Medicine 21, 14–16. Zhou, C., Byard, R.W., 2011. Armanni-Ebstein phenomenon and hypothermia. Forensic Science International 206, e82–e84.
Abstract The most common cause of lethal hypothermia is accidental exposure to low environmental temperatures, contributed to by inadequate or wet clothing, and damp or windy conditions. Other exacerbating factors include low muscle mass, alcohol and drug ingestion, trauma, open injuries, immobility, and certain underlying illnesses. Those at the extremes of age are at highest risk. Typical findings at autopsy include superficial gastric lesions, so-called Wischnewski spots, pink discoloration of the skin over the large joints, acute pancreatic inflammation with fat necrosis, fatty change in cells of the heart, liver and kidneys, skeletal muscle hemorrhage, and vacuolization of renal tubular cells.
Introduction Hypothermia occurs when the core temperature of the body falls below 35 1C. It is characterized by subtle morphological findings with complex underlying pathology and is a recognized, although probably underestimated, cause of death in man (Turk, 2010; Mallet, 2002; Dettmeyer, 2011). As humans are homeothermic organisms there is a need to constantly maintain a stable core body temperature despite changes in the surrounding environment (Reuler, 1978; Madea et al., 2008). Deviation in core body temperature below normal levels will have significant effects on thermoregulatory control and metabolic processes (Reuler, 1978; Bristow, 1984), with a greater than 70% mortality when the core temperature drops to 30 1C, and 90% at 26 1C (Zhou and Byard, 2011). Hypothermia can be graded as mild (o35 1C), moderate (35–32 1C), or severe (o32 1C). The most common cause of lethal hypothermia is accidental exposure to low environmental temperatures exacerbated by a number factors such as inadequate or wet clothing, damp conditions, wind, low muscle mass, alcohol ingestion and alcoholism, certain drugs, trauma, open injuries, immobility, cardiovascular, neurological, and endocrine disorders, and psychiatric illness. Individuals at the extremes of age are at highest risk (Matz, 1972; Zhou and Byard, 2011).
Problems in Diagnosis In forensic pathology, the diagnosis of fatal hypothermia may be problematic due to the subtlety of morphological features, nonspecific findings at autopsy, variability and difference in the frequency of diagnostic findings, and the possibility of suspicious circumstances due to aberrant behavior prior to death (Wedin et al., 1979; Rothschild and Schneider, 1995; Figure 1). As it is not usual to have the core temperature of a decedent at the time of death the diagnosis of lethal hypothermia, therefore, relies upon assessing the circumstances of the death (including the ambient temperature) and the exclusion of other factors (Preuß et al., 2004; Madea et al., 2008).
Subtle morphological features
Nonspecific findings at autopsy
Pathophysiology When the human body is exposed to decreased environmental temperatures the hypothalamus activates and initiates several counter-regulatory mechanisms such as vasoconstriction and chemical thermogenesis. (Caroselli et al., 2009; Nirula and Gentilello, 2005; Lonning et al., 1986). However, as the temperature declines further, heat loss exceeds heat production and thermoregulatory mechanisms begin to fail (Turk, 2010;
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Emslie-Smith, 1958). Lethal mechanisms include ventricular fibrillation or asystole, contributed to by myocardial ischemia, hypoxia, electrolyte abnormalities, and elevated catecholamine levels (Zhou and Byard, 2011).
Hypothermia
Possible high variability/ frequency of diagnostic findings
Suspected suspicious circumstances
Figure 1 Problems that occur with the diagnosis of hypothermia.
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Extremes of Temperature: Hypothermia
Difficulties may arise from unusual behavior associated with falling core temperatures, such as paradoxical undressing due to thermoregulatory failure where a person may be found semi-naked lying in snow with a trail of clothing left behind them. Similarly the ‘hide and die’ syndrome may occur in confused elderly recluses who are found hidden, for example, in a laundry under a pile of newspapers (Prahlow and Byard, 2012). Problems in assessment in the latter situation may be further compounded if the decedent suffered from Diogenes, or so-called senile squalor, syndrome where elderly socially isolated individuals live in domestic squalor with self neglect and hoarding (Bright et al., 2013a; Byard and Tsokos, 2007; Byard, 2014).
Morphological Features of Fatal Hypothermia Unfortunately the morphological features of hypothermia are neither specific nor diagnostic (Tables 1 and 2) and variability in the frequency of these changes further complicates the assessment of deaths (Wolf et al., 1999; Turk, 2010). Typical findings include pink discoloration of the skin over the extensor surfaces of large joints, such as the elbows, knees, and hips (Figure 2), acute pancreatic inflammation with fat necrosis, fatty change in cells of the heart, liver and kidneys, skeletal muscle hemorrhage, vacuolization of renal tubular cells, and probably the most significant finding, that of superficial gastric lesions, that have been called Wischnewski spots (Bright et al., 2013a). Frost bite may be observed in individuals who have survived for some time at temperatures below 0 1C due to tissue damage from freezing with peripheral circulatory failure.
Wischnewski Spots In 1895, Wischnewski observed multiple dark to black superficial hemorrhagic lesions of the gastric mucosa in deaths due to hypothermia (Figure 3). A contemporary translation of his original paper states: Table 1
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On the mucous membrane of the stomach in humans who have died exclusively from the effects of low temperatures, 5 to 100 hemorrhages are invariably present. Their size ranges from 0.5 to 1.0 cm. They have a round to oval form. Sometimes they are punctiform and lie about 1 to 2 in. apart. These hemorrhages are raised slightly above the surface of the mucous membrane, can be very easily scrapped (sic) away and leave behind nothing conspicuous on the gastric mucosa. (Wischnewski, 1895; Ehlrich, 2004)
Although not considered pathognomonic of hypothermia, Wischnewski spots have been accepted as the most reliable indicator of significantly reduced core temperature (Birchmeyer and Mitchell, 1989; Sperhake et al., 2004; Turk, 2010; Madea et al., 2008; Dettmeyer, 2011). Wischnewski spots vary in frequency, being found in 40–91% of cases in different series (Table 3; Dettmeyer, 2011; Madea et al., 2008). While Wischnewski reported a high incidence of 91% (Wischnewski, 1895), Hirvonen (1976) observed them in only half of the studied cases, describing them as scarce and irregular. Variation in frequency of Wischnewski spots may depend on circumstances of death, duration of exposure to cold stimulus, an individual’s reaction to cold stress and the resistance of the gastric mucosa to significantly decreased temperatures (Hirvonen, 1976; Madea et al., 2008; Wolf et al., 1999). Although Wilschnewski described raised hemorrhagic areas that could be easily removed from the mucosa, they were later considered to be ulcers or erosions. In an immunohistochemical study by Tsokos et al. (2006), however, it was proposed that the lesions resulted from the action of gastric acid on hemoglobin in areas of interstitial mucosal hemorrhage, and not from ulceration. Conversely, Hirvonen and Elfving (1974) reported that the erosions extended ‘halfway through the mucosa’ and that hemorrhage was ‘not always present.’ It appears most likely to the authors that lesions of different ages and/or severity may have different appearances and that erosions or ulcers may result from loss of friable and necrotic material arising from hemorrhage within the superficial layers of the gastric mucosa Figure 4.
Summary of the main external morphological features of hypothermia
External feature
Description
Pathophysiology
Frequency
Specificity
Blistering of skin Frost erythema
Local blistering Pinkish, purple discoloration of skin over large extensor joints (elbow, knee, and hip), sometimes projecting areas (ears, nose, and male genitalia)
Unknown Variable: 54–75%
Nonspecific Nonspecific
Hematomas/abrasions
Cutaneous lesions, reddening abrasions on elbows, and knees
Exposure to cold damages tissue Unclear; – Pronounced vascular hyperemia in subepidermal soft tissue – Capillary damage – Damaged erythrocytes – Plasma/ hemoglobin leakage into tissues Terminal burrowing behavior prior to death
Variable: depends on circumstances of death
Nonspecific
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Table 2
Extremes of Temperature: Hypothermia
Summary of the main internal morphological features of hypothermia
Internal feature
Description
Pathophysiology
Frequency
Specificity
Bright red blood and lividity
Blood appears bright red
Left shifting of oxygen-hemoglobindissociatian curve
Nonspecific
Hemorrhaging into core muscles
Specifically the illiopsoas muscle
Case dependent decreased diagnostic value as these changes can occur postmortem Rare finding
Wischnewski ulcers
– Superficial hemorrhagic dark blackish brown ‘leopard skin’ lesions of gastric mucosa – Necrosis with hematin formation – Characteristic linear pattern
Pancreatic changes
Fatty changes
Vacuolisation cells
Acute/hemorrhagic pancreatitis. Patches of fat necrosis on organ surface, raised serum amylase levels, focal/ diffuse infiltration of leukocytes, inflammation, vacuolisation of adenoid cells Heart liver and kidneys
Liver, pancreas, renal, and adrenal cells
Unclear;
– Hypoxic damage – Diapedesis – Insufficient circulation due to hypothermia-induced vasoconstriction – Misbalance of decreased perfusion and oxygen requirement Unclear; – Autolysis – Erythrocytes destroyed – Hemoglobin release – Disturbances of microcirculation – Involvement of tissue amines – Ischemic reperfusion – Increased capillary permeability and mucosal congestion Unclear; – Thrombosis in microcirculation that results in ischemia and perilobular necrosis – Vacuolisation due to impaired exocytosis and permeability
Unclear; possibly a result of energy depletion due to post shockinduced hypoxia – Tubular reabsorption following increased mobilization of triglycerides Loss of glycogen
Figure 2 Pink discoloration over both knees in a case of lethal hypothermia.
Nonspecific
40–100% cases dependent on exposure, resistance to cold and the individual
Nonspecific, however, most reliable feature of significantly reduced temperatures
Variable 20–30%
Nonspecific
Variable; case dependent
Nonspecific
Rare-variable
Nonspecific
Figure 3 Wischnewski spots in the gastric mucosa in a case of fatal hypothermia producing a typical ‘leopard skin’ effect.
Extremes of Temperature: Hypothermia
The exact etiology of these lesions remains unclear, however, their pathogenesis has been attributed to disturbances in microcirculation, involvement of tissue amines, breakdown of hemoglobin and ischemic-reperfusion injury (Madea et al., 2008; Tsokos et al., 2006; Wolf et al., 1999; Hirvonen and Elfving, 1974; Sperhake Table 3 Frequency of Wischnewski spots in cases of fatal hypothermia Frequency (%)
Sample
References
91.3 91 88 86 79 64 60 B50 44 40
23 44 25 43 24 67 15 22 23 30
Thrun (1992) Wischnewski (1895) Gillner and Waltz (1971) Mant (1969) Lim and Duflou (2008) Nikolic et al. (2010) Birchmeyer and Mitchell (1989) Hirvonen (1976) Mizukami et al. (1999) Kinzinger et al. (1995)
Age-related vulnerability Elderly, infants and young children Environment Temperature
Drugs and alcohol Hypothermic death
Underlying medical conditions
Social factors Diogenes syndrome Place of discovery Indoors vs outdoors
Figure 4 Various demographic and epidemiologic parameters associated with death due to hypothermia.
Table 4
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et al., 2004; Table 3). While stress may also be involved in the pathogenesis of Wischnewski spots, it is unclear if the gastric lesions develop due to stress caused by hypothermia or as a direct result of significantly reduced core body temperature (Takada et al., 1991; Birchmeyer et al., 1989; Wolf et al., 1999). A number of rodent models have been developed to test this possible association, with reports that stress, in conjunction with the integrity of higher order processing systems plays an important role in their development (Table 4). For example, Vincent et al. (1984) reported that aggressive behavior and an ability to decrease stress with access to a biting mechanism during cold exposure, had a protective effect by counteracting the effects of hypothermia, as rats showed fewer and smaller gastric lesions. The authors have recently developed an animal model which failed to generate Wischnewski spots in rats that were taken from a relatively low stress environment and exposed to decreased temperatures for a number of hours (Bright et al., 2013b). The absence of Wischnewski spots in animals that had died of hypothermia provides further support for stress being an important cofactor in the development of these lesions. The absence of renal vacuoles could also be explained by a similar mechanism (Zhou et al., 2014).
Pancreatic Changes A wide range of pancreatic changes in deaths due to hypothermia have been described that vary in both frequency and type (Table 5). While acute pancreatitis has been identified in hypothermic adults (Foulis, 1982; Mant, 1969; Symbas et al., 1961; Read et al., 1961), there are many contradictory findings between studies, with reports that hemorrhage and inflammatory changes of the pancreas are not reliable indicators of these deaths (Stiff et al., 2003; Preuß et al., 2006). The possibility of other causal factors in the pathogenesis of acute pancreatitis such as alcohol abuse, gall stones, trauma, and shock also means that it is unclear whether pancreatic changes are a primary or a secondary event (Foulis, 1982; Preuß et al., 2007).
Animal models of hypothermia involving stress
Animal (rat) models of hypothermia
References
Histamine and serotonin in the gastric erosions of rats dead from exposure to cold: a histochemical and quantitative study Role of hypothermia in the production of gastric ulcers in a rat spinal cord transection model Aggression, body temperature and stress ulcer Age-related differences in response to acute cold challenge ( 10 1C) in male F344 rats
Hirvonen and Elfving (1974)
Analysis of the cold water restraint procedure in gastric ulceration and body temperature Hydrogen sulphide-induced hypothermic attenuates stress-related ulceration in rats
Sigman and Gillich (1981) Vincent et al. (1984) Kiang-Ulrich and Hovarth (1985) Landeira-Fernandez (2004) Lou et al. (2008)
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Table 5
Extremes of Temperature: Hypothermia
Frequency and type of pancreatic changes in cases of fatal hypothermia
Frequency (%)
Type of change
Sample
References
73 67 63 38 25 18
Raised serum amylase levels Focal necrosis of adipose tissue and hemorrhagic pancreatitis Necrosis of the pancreas Hemorrhagic pancreatitis, focal pancreatitis with necrosis of adipose tissue Marked congestion and interstitial hemorrhage Macroscopically visible pancreatic hemorrhages, nonhemorrhagic, and hemorrhagic pancreatitis Focal and diffuse pancreatitis (post therapeutic hypothermia)
15 43 8 13 8 22
Duguid et al. (1961) Mant (1969) Foulis (1982) Duguid et al. (1961) Foulis (1982) Hirvonen (1976)
50
Sano and Smith (1940)
10
While Mant described hemorrhagic pancreatitis in 67% of fatal hypothermic cases (Mant, 1969), Preuß et al. (2007) showed macroscopic hemorrhage of the pancreas without acute inflammation in only 4% of cases. The difference in frequency and type of pancreatic changes between investigations may, however, be due to variations in sample size and methodology. For example, while Preuß et al. had a large sample of 143 cases, retrospective review may have resulted in underreporting. The review of Mant’s 49 cases may have also been skewed by an overrepresentation of the elderly with the possibility of preexisting pancreatic diseases (Mant, 1969; Preuß et al., 2007). Three possible mechanisms were proposed by Foulis in 1982 for the relationship between acute pancreatitis and hypothermia that involved:
• • •
Ischemic pancreatitis, from the microcirculatory shock of hypothermia Hypothermia and acute pancreatitis, secondary to alcohol abuse Severe pancreatitis as primary disease with hypothermia resulting from social circumstances (Foulis, 1982).
Epidemiology Numerous epidemiological studies of the morbidity and mortality of hypothermia have retrospectively reviewed data on hypothermic cases from hospital admissions, autopsy records, coronial reports and national mortality statistics (Table 6). These have recognized that exposure to significantly decreased temperatures is not the only factor in these deaths (Thomas, 1988; Herity et al., 1991; Lim and Duflou, 2008; Danzl et al., 1987; McKee, 1989, 1990).
Age-Related Vulnerability The extremes of age are associated with increased morbidity and mortality associated with hypothermia (Taylor et al., 2001; Glickman et al., 2002; Megarbane
et al., 2000; Herity et al., 1991; Reuler, 1978; Wagner and Horvath, 1985; Altus et al., 1980; Collins et al., 1977; Thomas, 1988; Elbaz et al., 2008; Sloan and Keatinge, 1973). Infants and young children have an increased risk due to their lack of muscle mass and adiposity and their increased surface area to body mass ratio (Sloan and Keatinge, 1973; Turk, 2010). There are, however, relatively few studies into hypothermic deaths in children. The elderly also are more susceptible to the effects of hypothermia due to failing biological mechanisms of temperature regulation, such as vasoconstriction and shivering, not being sufficient to maintain the balanced relationship between heat loss and heat production. The elderly are also less able to discern cold temperatures due to possible autonomic nervous system dysfunction and may not dress appropriately, thus increasing body heat loss. Elderly recluses often do not use heating in an attempt to be ‘thrifty,’ particularly in the face of rising electricity and oil prices (Bright et al., 2013a; Thomas, 1988; Herity et al., 1991; Megarbane et al., 2000; Taylor et al., 2001; Elbaz et al., 2008; Dharmarajan and Widjaja, 2007; Krag and Kountz, 1950; Watts, 1971). Kiang-Ulrich and Hovarth (1985) using an animal model also showed that responses to acute cold exposure deteriorate with age (Table 4). Thomas et al. in a 10-year review of hospital discharge codings and mortality rates showed that elderly individuals were disproportionately represented, accounting for 65% of hypothermic deaths. The higher incidence of deaths in the elderly was attributed to abnormal temperature perception and regulation, intercurrent illnesses, social isolation, and inadequate housing or poverty (Thomas, 1988). Collins et al. concluded that both physiologic and behavioral factors involved in poor temperature discrimination, age-related decline in efficiency of cold-defence mechanisms and a lack of adjustment of the thermal environment all contribute to the increased vulnerability and susceptibility of the elderly cohort (Collins et al., 1981, 1977; Collins, 1986). A caveat in the assessment of age-related variables associated with hypothermia relates to differences in sample sizes and methods of evaluation (Table 6); for example, studies of healthy retired individuals with no
Table 6
Retrospective reviews of the morbidity and mortality of hypothermia in varying populations
Author/Year
Period
Location
Method
Sample
Key findings
Altus et al. (1980)
5 years
Tampa, FL, USA
Case reports from hospital admissions
4 case reports
– Predicted that hypothermia will become
Discharge codings of preceding 10 years at University of Mississippi Medical Center Reviewed for hypothermia, abnormal temperature, or environment related illness
35 patients with hypothermia diagnosis
more prevalent in warmer climates in the future – Inadequacy of insulation of homes for cold temperatures Extreme environmental conditions not only factor required to produce hypothermia; other factors involved Indoors 71% cases Outdoors 29% cases Male 75%
Thomas (1988)
10 years (1968–1980)
Jackson, MI, USA
34 patients able to be reviewed 24 primary hypothermia 10 secondary hypothermia
5 years (1933–1988)
Onondaga County, NY, USA
County Medical Examiner's office
16 deaths 15 autopsies
Tanaka and Tokudome (1990)
1974–1933
Tokyo, Japan
Autopsy records/reports from Medical Examiner's office
157 deaths
Herity et al. (1991)
1979–1985
Republic of Ireland
Survey of deaths and hospital admissions due to hypothermia identified from death certificates and Hospital in patient data
453 deaths recorded
Megarbane et al. (2000)
17 years (1931–1998)
Paris, France
Retrospective clinical investigation in a medical ICU
81 patients
491
Death 37% 65% Elderly Single most precipitating factor; ingestion of alcohol 33% cases – 9 cases definitive petechial/ulcerative changes in gastric mucosa – Pattern of ulceration is as important as the presence of Wischnewski ulcers – Suggested protective effects of alochol – Male predominance (143 M, 14 F) – 77% Outdoor cases, 23% Indoors – Majority attributed to alcoholism (few cases showed no evidence of alcoholism) – Age: 40–50 years 60% cases – Incidence in Male vs. Female was similar – Males had a 30% increased fatality – Hypothermia statistics must be interpreted cautiously – Incidence and Mortality increased with age – Outdoors 21% cases – Indoors 79% cases – 36% died – Patients found indoors more severely affected and greater mortality rate – Age predictive factor of death (Continued )
Extremes of Temperature: Hypothermia
Birchmeyer and Mitchell (1989)
Black 71%
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Table 6
Continued
Author/Year
Period
Location
Method
Sample
Key findings
underlying cause of hypothermia Roeggla et al. (2001)
1991–1998
Vienna, Italy
Retrospective cohort study of patients admitted to ED
80 patients
Taylor et al. (2001)
1983–1999
Jefferson County, AL, USA
Autopsy reports coronial investigations
63 cases
Elbaz et al. (2008)
6 years (1999–2005)
Beer Sheva, Southern Israel
Retrospective study: Soroka University Medical Center
169 patients
Admissions to hospital with diagnosis of hypothermia
Lim and Duflou (2008)
5 years (2001–2005)
Sydney, Australia
Electronic Autopsy records
95 cases 24 fatal hypothermia
– 34% mortality rate – Hypothesized that predisposing conditions in urban settings may aggravate hypothermia and the damage it induces – Psychological problems are major contributing factor – Majority of patients had complex medical history – Indoor hypothermia is a special type of hypothermia – Increased rate among blacks and males 80 years þ – Two main groups affected elderly and middle-aged males – Chronic mental conditions 90% cases – Criteria for assigning hypothermia as cause of death may not be uniform among jurisdictions; comparison is, therefore, difficult – Hospital mortality rate 47.3% – Indoor hypothermia associated with a worse outcome – Risk of hypothermia present in warmer months also, not limited to cold climates – Majority of patients had major medical conditions contributing to presence and severity of hypothermia – Greater incidence in individuals 75 years þ – Female predominance 63% – Deaths occurred in all seasons – Gastric Wischnewski erosions 79% cases – Paradoxical undressing 29% cases – All cases had significant preexisting natural disease process – Elderly most affected average age: 76 years
Extremes of Temperature: Hypothermia
– Suggested that associated illness is primary
Extremes of Temperature: Hypothermia
medical conditions may not be representative of the general population (Schellan et al., 2010).
Underlying Disorders Associated with Hypothermia A wide range of natural diseases have been identified as predisposing factors to death from hypothermia (Turk, 2010; Megarbane et al., 2000; McKee, 1990; Taylor et al., 2001; Table 6). These diseases are mostly agerelated (Elbaz et al., 2008; Lim and Duflou, 2008; Megarbane et al., 2000; Roeggla et al., 2001; Thomas, 1988). Conditions contributing to hypothermia include hypothyroidism; diabetes mellitus; trauma; sepsis; stroke; and renal, heart, and liver failure (Maclean et al., 1973; Elbaz et al., 2008; Megarbane et al., 2000; Roeggla et al., 2001). It is felt that these conditions interfere with thermoregulation, predispose to abnormal temperature control and regulation and have the potential to aggravate and enhance tissue damage induced by hypothermia (Roeggla et al., 2001). An additional problem in the forensic evaluation of cases is that these conditions may mask the mechanism of death (Lim and Duflou, 2008; Elbaz et al., 2008). Mental illnesses such as schizophrenia, bipolar disorder, Alzheimer’s disease, and dementia have also been identified as potential risk factors for hypothermic deaths (Taylor et al., 2001; Lim and Duflou, 2008). Alcohol intoxication is a well known factor in certain hypothermic fatalities for a variety of reasons, occurring in up to 64% of cases in some series (Tanaka and Tokudome, 1990). Alcohol promotes heat loss via the dilation of superficial blood vessels and may render individuals incapable of removing themselves from a cold environment (Taylor et al., 2001; Kalant and Le, 1984). Interestingly, it has been suggested that alcohol may reduce the incidence of Wilschnewski spots by reducing physiologic stress (Birchmeyer and Mitchell, 1989). The most frequent location of hypothermic deaths associated with alcohol has been outdoors with 40- to 50-year-old males being most susceptible (Tanaka and Tokudome, 1990; Taylor et al., 2001).
Sex and Racial Differences Differences in percentages of males and females in various studies may be attributed to a variety of causes. For example, a male predominance occurring in outdoor deaths may be related to specific activities such as skiing and to intoxication. Tanaka and Tokudome (1990) reported a 91% incidence of hypothermic deaths in males, compared to Lim and Duflou who reported a female predominance of 63% (Lim and Duflou, 2008). Sex differences in incidence may relate to variations in adiposity, muscle mass and metabolic responses between
493
males and females (Anderson et al., 1995; Keatinge, 1960; Budd and Warhaft, 1966; Wagner and Horvath, 1985). The frailty syndrome occurs in the elderly who have reduced ambulation and significant loss of skeletal muscle bulk with lowering of the body mass index. Given that lighter bodies lose heat more rapidly than heavier bodies this may also be a predisposing factor to lethal hypothermia that would contribute to the higher numbers of female deaths indoors. Although black individuals have been identified in some studies as being more susceptible to hypothermia and its effects, other studies have found no significant influence of race on thermosensitivity (Turk et al., 2005, 2006; Thomas, 1988; Taylor et al., 2001; Farnell et al., 2008).
Location of Deaths Deaths from hypothermia indoors are well documented (Roeggla et al., 2001; Megarbane et al., 2000; Tanaka and Tokudome, 1990; Elbaz et al., 2008). It has been suggested that victims found indoors may experience longer exposure to the cold and have a lowered cooling rate, whereas outdoor victims, although exposed to lower temperatures, may experience a shorter cooling time (Roeggla et al., 2001). Megarbane et al. reported 79% of hypothermic deaths occurring indoors, describing victims as generally older with underlying disorders that led to a higher risk of mortality compared to subjects found outdoors (Megarbane et al., 2000; Elbaz et al., 2008). This was the finding in studies in South Australia that found inadequate heating and insulation, individual vulnerability, lack of awareness of hazards associated with hypothermia, and a lack of preparation for cold weather, all contributed to fatal outcomes (Bright et al., 2012, 2013a). The colder months of the year are known to be associated with an increase in death rates usually associated with cardiovascular and respiratory illnesses in the elderly. This has ranged from 5% to 30% and has been termed the excess winter mortality. Although hypothermic deaths contribute to this they are not limited to colder climates, with a recent study showing slightly higher death rates from hypothermia in South Australia (3.9/ 100 000) and Sweden (3.3/100 000), despite the obvious differences in external temperatures (average temperature in South Australia¼20 1C, and in Sweden¼10 1C) (Bright et al., 2014). A previous review in Sydney, Australia, also highlighted the significance of fatal hypothermia as a public health problem in warmer climates (Lim and Duflou, 2008). Similarly Elbaz et al. (2008) investigated the severity and mortality of hypothermia in the desert climate of Southern Israel, concluding that hypothermia should not be overlooked in regions with temperate climates, as the risk of hypothermia was present even during the warmest months of the year.
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Extremes of Temperature: Hypothermia
Conclusions It is clear that hypothermia has a complex pathophysiology with numerous parameters that contribute to the associated morbidity and mortality. The diagnosis at postmortem may be very difficult and may be missed unless adequate death scene information is available. The sensitivity, specificity and etiology of the typical morphologic changes are, however, incompletely understood.
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