Heat-Related Deaths in Hot Cities: Estimates of Human Tolerance to High Temperature Thresholds

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Supplementary Information Heat-Related Deaths in Hot Cities: Estimates of Human Tolerance to High Temperature Thresholds Selection of ICD-10 Codes Indicating Conditions and Diseases that Might Be Directly or Indirectly Related to Heat Diana B. Petitti, M.D., M.P.H. We selected ICD-10 codes indicating conditions that might be directly or indirectly related to exposure to high environmental temperature based on: (1) knowledge of the direct physiologic effects of exposure to high environmental temperature and the downstream consequences of these physiologic effects on the body; and (2) the results of extensive prior work of others on temperature-mortality relationships. Eight categories of conditions and diseases used in our analysis are described in more detail below. The first three categories were conditions directly due to exposure to high environmental heat; dehydration (and direct consequence of exposure to high environmental heat); and conditions that are possible consequences of heat exposure and/or dehydration. The last five categories, cardiac disease/stroke, chronic renal failure, heart failure, COPD/asthma, and other respiratory illnesses have been prominent in prior analyses of the association of high environmental heat with death and hospitalization. Supplemental Table S1 provides a complete list of codes for causes of death in each category and the terms associated with exposure to high environmental heat that are entered as free text in any of the underlying cause of death fields in the first three categories. Direct Exposure to Environmental Heat In the human, exposure to high environmental heat is often accompanied by exposure to the sun. Thus, the first set of ICD-10 codes are for conditions that include the terms sunburn, sun exposure, and/or ultraviolet light. These were located by doing a text search of the online version of the ICD-10. The second set of ICD-10 codes identified as being due to the direct effect of heat are those that include the term heat. These were also located by doing a text search of the online version of the ICD-10. Dehydration In the human, exposure to high environmental heat is accompanied by sweating and fluid loss. The consequence of fluid loss is dehydration, which is followed by volume depletion and hypovolemia. ICD-10 codes that included the term dehydration were identified by doing a text search of the online version of the ICD-10.

S2 Possible Consequences of Heat and Dehydration In the human, exposure to high environmental heat is accompanied by sweating and fluid loss. The consequence of fluid loss is dehydration, which is followed by volume depletion and hypovolemia. Supplemental Figure S1 is a graphical depiction of the model that explains our approach to selecting codes considered likely to be due to the physiologic and pathophysiologic consequences of heat and dehydration/volume depletion/hypovolemia. Volume depletion and hypovolemia can cause hypotension. Hypotension can lead to shock, coma and sudden death. Dehydration/volume depletion/hypovolemia can lead to the formation of kidney stones and thus to renal colic. Hypovolemia can lead to hemoconcentration and cause disturbances in serum electrolytes (sodium hypernatremia and potassium hyperkalemia) and osmolality (hyperosmolality). The disturbances of serum electrolytes can lead to arrythymias, coma, and sudden death. Hypovolemia can lead to acute renal failure. Thirst is a physiologic response to dehydration. When water is consumed in response to thirst without adequate electrolytes, the consequence can be disturbances in serum electrolytes (sodium hyponatremia and potassium hypokalemia) and osmolality (hypo-osmolality). Disturbances in serum electrolytes can lead to arrythymias, coma, and sudden death. One consequence of heat and dehydration is hyperthermia, which can directly cause arrhythmias, and can lead to shock, coma, and sudden death. Hyperthermia also can lead to fever and then febrile convulsions. Hyperthermia may cause disseminated intravascular coagulation (DIC). A number of the consequences of heat and dehydration (e.g., hypotension) can cause malaise and fatigue. Malaise and fatigue are also symptoms of hyperthermia and also of hypovolemia. Dizziness and giddiness is a condition with a specific ICD-10 code that has been identified in other studies as having a relationship to ED visits and hospitalization during heat waves. We selected the ICD-10 codes that corresponded to the other named conditions that are a consequence of heat and dehydration by reading the ICD-10 code book and using information in the publications of others. Cardiac Disease/Stroke Studies of excess mortality and morbidity in heat waves consistently find an association with atherosclerotic heart disease and stroke. The description of the physiologic and pathophysiologic consequences of heat and dehydration provide ample explanation for an effect of heat on mortality and morbidity due to atherosclerotic heart disease and stroke. Hypotension, hemoconcentration, and electrolyte disorders would all be expected to exacerbate the severity of underlying vascular disease and/or lead to coronary or cerebral thrombosis. We selected the set of ICD-10 codes for atherosclerotic vascular disease that have been used by other researchers noting that the link between hemorrhagic stroke (including subarachnoid hemorrhage) and heat/dehydration and its consequences seems tenuous.

S3 Chronic Renal Failure Chronic renal failure is associated with a multiplicity of underlying abnormalities of fluid and electrolyte metabolism. Many people with chronic renal failure are being dialyzed. An effect of heat and dehydration and their consequences in exacerbating the severity of chronic renal failure and even perhaps causing death in a person with chronic renal failure has high biologic plausibility. We selected all of the ICD-10 codes for chronic renal failure. Heart Failure Heart failure is associated with a multiplicity of underlying abnormalities in handling fluids. People with heart failure are at increased risk of atrial fibrillation and are vulnerable to other cardiac arrhythmias. They are also at increased risk of stroke. An effect of heat and dehydration and their consequences in exacerbating the severity of heart failure or causing death in a person with heart failure has high biologic plausibility. We selected the ICD-10 codes for heart failure for this category. We also selected the ICD-10 codes for unspecified cardiovascular disease, other and ill-defined heart disease and unspecified heart disease for this category based on the belief that many people who have these non-specific codes listed as a cause of death would have heart failure. Chronic Obstructive Pulmonary Disease (COPD)/Asthma Other Respiratory Diseases Some prior research on deaths and hospitalizations in the context of extreme heat has found strong associations with respiratory illnesses. Following Semenza et al. [1] and Schwartz [2], we examined chronic obstructive pulmonary disease (COPD) and asthma separately from infections, influenza, and other respiratory diseases. References 1. Semenza, J.C.; McCullough, J.E.; Flanders, W.D.; McGeehin, M.A.; Lumpkin, J.R. Excess hospital admissions during the July 1995 heat wave in Chicago. Am. J. Prev. Med. 1999, 16, 269 277. 2. Schwartz, J. Who is sensitive to extremes of temperature? A case-only analysis. Epidemiology 2005, 16, 67 72.

S4 Table S1. ICD-10 codes for conditions and diseases directly and indirectly related to high environmental heat. Direct Exposure to Environmental Heat L55 Sunburn L55.0 Sunburn of first degree L55.1 Sunburn of second degree L55.2 Sunburn of third degree L55.8 Other sunburn L55.9 Sunburn, unspecified L56 Other acute skin changes due to ultraviolet radiation L56.0 Drug phototoxic response L56.1 Drug photoallergic response L56.3 Solar urticaria L56.4 Polymorphous light eruption L56.8 Other specified acute skin changes due to ultraviolet radiation L56.9 Acute skin change due to ultraviolet radiation, unspecified T67 Effects of heat and light T67.0 Heatstroke and sunstroke T67.1 Heat syncope T67.2 Heat cramp T67.3 Heat exhaustion, anhydrotic T67.4 Heat exhaustion due to salt depletion T67.5 Heat exhaustion, unspecified T67.6 Heat fatigue, transient T67.7 Heat oedema T67.8 Other effects of heat and light T67.9 Effect of heat and light, unspecified X30 Exposure to excessive natural heat X32 Exposure to sunlight Keywords: b Environmental Heat, Excessive Heat, Excessive Natural Heat, Exposure to Heat, Exposure to Heated Environment, Exposure to High Environmental Temperature, Exposure to Hot Desert Environment, Exposure to Hot Environment, Heat Cramps, Heat Effect, Heat Environment, Heat Exhaustion, Heated Environment, Heat Exposure, Heat Related, Heat Stress, Heatstroke, Heat Syncope, High Environmental Temperature, Hiking in Hot Climate, Hot Outside, Sunburn, Sun Exposure, Temperature.

S5 Dehydration E86 Volume depletion P74.1 Dehydration of newborn R68.2 Dry mouth, unspecified X54 Lack of water Keyword: b Dehydration. Possible Consequences of Heat or Dehydration D65 Disseminated intravascular coagulation [defibrination syndrome] E87.0 Hyperosmolality and hypernatremia E87.1 Hypo-osmolality and hyponatremia E87.4 Mixed disorder of acid-base balance E87.5 Hyperkalemia E87.6 Hypokalemia I46 Cardiac arrest I46.0 Cardiac arrest with successful resuscitation I46.1 Sudden cardiac death, so described I46.9 Cardiac arrest, unspecified I47 Paroxysmal tachycardia I47.0 Reentry ventricular arrhythmia I47.1 Supraventricular tachycardia I47.2 Ventricular tachycardia I47.9 Paroxysmal tachycardia, unspecified I48 Atrial fibrillation and flutter I49 Other cardiac arrhythmias I49.0 Ventricular fibrillation and flutter I49.1 Atrial premature depolarization I49.2 Junctional premature depolarization I49.3 Ventricular premature depolarization I49.4 Other and unspecified premature depolarization I49.5 Sick sinus syndrome I49.8 Other specified cardiac arrhythmias I95.0 Idiopathic hypotension I95.1 Orthostatic hypotension I95.8 Other hypotension I95.9 Hypotension, unspecified N17 Acute renal failure N17.0 Acute renal failure with tubular necrosis N17.1 Acute renal failure with acute cortical necrosis N17.2 Acute renal failure with medullary necrosis N17.8 Other acute renal failure N17.9 Acute renal failure, unspecified N20 Calculus of kidney and ureter N20.0 Calculus of kidney N20.1 Calculus of ureter

S6 N20.2 Calculus of kidney with calculus of ureter N20.9 Urinary calculus, unspecified N21 Calculus of lower urinary tract N21.0 Calculus in bladder N21.1 Calculus in urethra N21.8 Other lower urinary tract calculus N21.9 Calculus of lower urinary tract, unspecified N23 Unspecified renal colic P74.2 Disturbances of sodium balance of newborn P74.3 Disturbances of potassium balance of newborn P81.0 Environmental hyperthermia of newborn R00 Abnormalities of heart beat R00.0 Tachycardia,unspecified R00.1 Bradycardia,unspecified R00.2 Palpitations R00.8 Other and unspecified abnormalities of heart beat R40.2 Coma, unspecified R42 Dizziness and giddiness R50.9 Fever, unspecified R53 Malaise and fatigue R55 Syncope and collapse R56.0 Febrile convulsions R57.1 Hypovolemic shock R57.8 Other shock R57.9 Shock, unspecified R96 Other sudden death, cause unknown R96.0 Instantaneous death R96.1 Death occurring less than 24 hours from onset of symptoms, not otherwise explained R98 Unattended death Keywords: b Exhaustion, Hyperkalemia, Hypernatremia, Hyperther, Hyperthermia, Hypokalemia, Hyponatremia, Hypovolemia. Cardiac Disease/Stroke I20 Angina pectoris I20.0 Unstable angina I20.1 Angina pectoris with documented spasm I20.8 Other forms of angina pectoris I20.9 Angina pectoris, unspecified I21 Acute myocardial infarction I21.0 Acute transmural myocardial infarction of anterior wall I21.1 Acute transmural myocardial infarction of inferior wall I21.2 Acute transmural myocardial infarction of other sites I21.3 Acute transmural myocardial infarction of unspecified site I21.4 Acute subendocardial myocardial infarction I21.9 Acute myocardial infarction, unspecified I22 Subsequent myocardial infarction I22.0 Subsequent myocardial infarction of anterior wall

S7 I22.1 Subsequent myocardial infarction of inferior wall I22.8 Subsequent myocardial infarction of other sites I22.9 Subsequent myocardial infarction of unspecified site I24 Other acute ischemic heart diseases I24.1 Dressler s syndrome I24.8 Other forms of acute ischemic heart disease I24.9 Acute ischemic heart disease, unspecified I25 Chronic ischemic heart disease I25.0 Atherosclerotic cardiovascular disease, so described I25.1 Atherosclerotic heart disease I25.2 Old myocardial infarction I25.3 Aneurysm of heart I25.4 Coronary artery aneurysm I25.5 Ischemic cardiomyopathy I25.6 Silent myocardial ischemia I25.8 Other forms of chronic ischemic heart disease I25.9 Chronic ischemic heart disease, unspecified I49.9 Cardiac arrhythmia, unspecified I60 Subarachnoid hemorrhage I60.0 Subarachnoid hemorrhage from carotid siphon and bifurcation I60.1 Subarachnoid hemorrhage from middle cerebral artery I60.2 Subarachnoid hemorrhage from anterior communicating artery I60.3 Subarachnoid hemorrhage from posterior communicating artery I60.4 Subarachnoid hemorrhage from basilar artery I60.5 Subarachnoid hemorrhage from vertebral artery I60.6 Subarachnoid hemorrhage from other intracranial arteries I60.7 Subarachnoid hemorrhage from intracranial artery, unspecified I60.8 Other subarachnoid hemorrhage I60.9 Subarachnoid hemorrhage, unspecified I61 Intracerebral hemorrhage I61.0 Intracerebral hemorrhage in hemisphere, subcortical I61.1 Intracerebral hemorrhage in hemisphere, cortical I61.2 Intracerebral hemorrhage in hemisphere, unspecified I61.3 Intracerebral hemorrhage in brain stem I61.4 Intracerebral hemorrhage in cerebellum I61.5 Intracerebral hemorrhage, intraventricular I61.6 Intracerebral hemorrhage, multiple localized I61.8 Other intracerebral hemorrhage I61.9 Intracerebral hemorrhage, unspecified I62 Other nontraumatic intracranial hemorrhage I62.0 Subdural hemorrhage (acute) (nontraumatic) I62.1 Nontraumatic extradural hemorrhage I62.9 Intracranial hemorrhage (nontraumatic), unspecified I63 Cerebral infarction I63.0 Cerebral infarction due to thrombosis of precerebral arteries I63.1 Cerebral infarction due to embolism of precerebral arteries I63.2 Cerebral infarction due to unspecified occlusion or stenosis of precerebral arteries I63.3 Cerebral infarction due to thrombosis of cerebral arteries I63.4 Cerebral infarction due to embolism of cerebral arteries

S8 I63.5 Cerebral infarction due to unspecified occlusion or stenosis of cerebral arteries I63.6 Cerebral infarction due to cerebral venous thrombosis, nonpyogenic I63.8 Other cerebral infarction I63.9 Cerebral infarction, unspecified I64 Stroke, not specified as hemorrhage or infarction I67 Other cerebrovascular diseases I67.0 Dissection of cerebral arteries, nonruptured I67.1 Cerebral aneurysm, nonruptured I67.2 Cerebral atherosclerosis I67.3 Progressive vascular leukoencephalopathy I67.4 Hypertensive encephalopathy I67.5 Moyamoya disease I67.6 Nonpyogenic thrombosis of intracranial venous system I67.7 Cerebral arteritis, not elsewhere classified I67.8 Other specified cerebrovascular diseases I67.9 Cerebrovascular disease, unspecified I69 Sequelae of cerebrovascular disease I69.0 Sequelae of subarachnoid hemorrhage I69.1 Sequelae of intracerebral hemorrhage I69.2 Sequelae of other nontraumatic intracranial hemorrhage I69.3 Sequelae of cerebral infarction I69.4 Sequelae of stroke, not specified as hemorrhage or infarction I69.8 Sequelae of other and unspecified cerebrovascular diseases I70 Atherosclerosis I70.0 Atherosclerosis of aorta I70.1 Atherosclerosis of renal artery I70.2 Atherosclerosis of arteries of the extremities I70.8 Atherosclerosis of other arteries I70.9 Generalized and unspecified atherosclerosis Chronic Renal Failure N18 Chronic renal failure N18.0 End-stage renal disease N18.8 Other chronic renal failure N18.9 Chronic renal failure, unspecified N19 Unspecified renal failure Heart Failure I50 Heart failure I50.0 Congestive heart failure I50.1 Left ventricular failure I50.9 Heart failure, unspecified I51.6 Cardiovascular disease, unspecified I51.8 Other ill-defined heart diseases I51.9 Heart disease, unspecified

S9 Chronic Obstructive Pulmonary Diseases (COPD)/Asthma J43 Emphysema J43.0 MacLeod syndrome J43.1 Panlobular emphysema J43.2 Centrilobular emphysema J43.8 Other emphysema J43.9 Emphysema, unspecified J44 Other COPD J44.0 COPD with acute lower respiratory infection J44.1 COPD with acute exacerbation, unspecified J44.8 Other specified COPD J44.9 COPD, unspecified J45 Asthma J45.0 Predominantly allergic asthma J45.1 Nonallergic asthma J45.8 Mixed asthma J45.9 Asthma, unspecified J46 Status asthmaticus Other Respiratory Diseases J00-J06 Acute upper respiratory infections J09-J18 Influenza and pneumonia J20-22 Other acute lower respiratory infections J30-39 Other diseases of the upper respiratory tract J40-J42 Bronchitis J47 Bronchiectasis J60-J70 Lung diseases due to external agents J80-J84 Other respiratory diseases principally affecting the interstitium J85-J86 Suppurative and necrotic conditions of lower respiratory tract J90-J94 Other diseases of pleura J95-J99 Other diseases of the respiratory system a International Classification of Diseases, 10th Revision. b We searched the database for selected keyword terms entered as free text in any of the four underlying cause-of-death fields in Part I of the death certificate. Cases with keywords were included in one of the first three categories of death (i.e., direct exposure to environmental heat, dehydration, or possible consequences of heat and dehydration). Cases with keywords associated with more than one of these categories were assigned to the category most directly associated with heat; i.e., a case with a keyword from direct exposure to environmental heat and a keyword from possible consequences of heat and dehydration, was assigned to the first category.

S10 Figure S1. Approach to selection of ICD-10 codes for conditions that are likely due to physiologic and pathophysiologic consequences of heat and dehydration. Kidney Stone Renal Colic Loss of Fluid (Sweating) DEHYDRATION Volume Depletion Hypotension Acute Renal Failure HEAT Hyperkalemia Hypernatremia Hyper osmolality Syncope and Collapse Malaise and Fatigue Dizziness Thirst Increased Fluid Consumption Hypokalemia Hyponatremia Hypo osmolality Arrhythmia Shock Coma Sudden Death Hyperthermia DIC Fever Convulsion