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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

In a patient with sudden death, a thorough evaluation of potential causes is essential to exclude preventable causes of recurrence.

Cardiac Arrest: Overview of Causes

Cardiac arrest is synonymous with Clinical death. All disease processes leading to death have a period of (potentially) reversible cardiac arrest: the causes of arrest are, therefore, numerous. However, many of these conditions, rather than causing an arrest themselves, promote one of the "reversible causes" (see below), which then triggers the arrest (e.g. Choking leads to Hypoxia which in turn leads to an arrest). In some cases, the underlying mechanism cannot be overcome, leading to an unsuccessful resuscitation.

Among adults, ischemic heart disease is the predominant cause of arrest. At autopsy 30% of victims show signs of recent myocardial infarction. Other cardiac conditions potentially leading to arrest include structural abnormalities, arrhythmias and cardiomyopathies. Non-cardiac causes include infections, overdoses, trauma and cancer, in addition to many others.

Cardiac Arrest: Reversible Causes

Cardiopulmonary resuscitation (CPR), including adjunctive measures such as defibrillation, intubation and drug administration, is the standard of care for initial treatment of cardiac arrest. However, most cardiac arrests occur for a reason, and unless that reason can be found and overcome, CPR is often ineffective, or if it does result in a return of spontaneous circulation, this is short lived. . As highlighted above, a variety of disease processes can lead to a cardiac arrest, however they usually boil down to one or more of the "Hs and Ts" (see below).

H's

• Hypovolemia - A lack of circulating body fluids, principally blood volume. This is usually (though not exclusively) caused by some form of bleeding, anaphylaxis, or pregnancy with gravid uterus. Peri-arrest treatment includes giving IV fluids and blood transfusions, and controlling the source of any bleeding - by direct pressure for external bleeding, or emergency surgical techniques such as esophagogastroduodenoscopy (i.e. esophageal varices) and thoracotomy for internal bleeding.
• Hypoxia - A lack of oxygen to the heart, brain and other vital organs. This can be identified through a careful assessment of breath sounds and tuble placement. Treatment may include providing oxygen, proper ventilation, and good CPR technique.
• Hydrogen ions (Acidosis) - An abnormal pH in the body as a result of shock, Diabetic ketoacidosis, renal failure, or tricyclic antidepressant overdose. This can be treated with proper ventilation, good CPR technique, and buffers like sodium bicarbonate.
• Hyperkalemia or Hypokalemia - The most life threatening electrolyte derangement is hyperkalemia (too much potassium). The classic presentation is the chronic renal failure patient who has missed a dialysis appointment and presents with weakness, nausea, and broad QRS complexes on the electrocardiogram. The most important initial therapy is the administration of calcium, either with calcium gluconate or calcium chloride. Other therapies may include nebulized albuterol, sodium bicarbonate, glucose, and insulin. The diagnosis of hypokalemia (not enough potassium) can be suspected when there is a history of diarrhoea or malnutrition. Loop diuretics may also contribute. The electrocardiogram may show depressed T waves and prominent U waves. Hypokalemia is an important cause of acquired long QT syndrome, and may predispose the patient to torsades de pointes. Digitalis use may increase the risk that hypokalemia will produce life threatening arrhythmias.
• Hypothermia - A low core body temperature, defined clinically as a temperature of less than 35 degrees Celsius. The patient is re-warmed either by using a cardiac bypass or by irrigation of the body cavities (such as thorax, peritoneum, bladder) with warm fluids; or warmed IV fluids. CPR only is given until the core body temperature reached 30 degrees Celsius, as defibrillation is ineffective at lower temperatures. Patients have been known to be successfully resuscitated after periods of hours in hypothermia and cardiac arrest, and this has given rise to the often-quoted medical truism, "You're not dead until you're warm and dead."
• Hypoglycemia or Hyperglycemia - Low blood glucose from insulin reactions, DKA, nonketotic hyperosmolar coma. This condition can be suspected when the patient is known to be a diabetic. The treatment may include fluids, potassium, glucose (for hypoglycemia), and insulin (for hyperglycemia).

T's

• Tablets or Toxins - Tricyclic antidepressants, phenothiazines, beta blockers, calcium channel blockers, cocaine, digoxin, aspirin, acetominophen. This may be evidenced by items found on or around the patient, the patient's medical history (i.e. drug abuse, medication) taken from family and friends, checking the medical records to make sure no interacting drugs were prescribed, or sending blood and urine samples to the toxicology lab for report. Treatment may include specific antidotes, fluids for volume expansion, vasopressors, sodium bicarbonate (for tricyclic antidepressants), glucagon or calcium (for calcium channel blockers), benzodiazepines (for cocaine), or cardiopulmonary bypass.
• Cardiac Tamponade - Blood or other fluids building up in the pericardium can put pressure on the heart so that it is not able to beat. This condition can be recognized by the presence of a narrowing pulse pressure, muffled heart sounds, distended neck veins, electrical alternans on the electrocardiogram, or echocardiogram. This is treated in an emergency by inserting a needle into the pericardium to drain the fluid (pericardiocentesis), or if the fluid is too thick then an emergency thoracotomy is performed to cut the pericardium and release the fluid.
• Tension pneumothorax - The build up of air into one of the pleural cavities, which causes a mediastinal shift. When this happens, the great vessels (particularly the superior vena cava) become kinked, which limits blood return to the heart. The condition can be recognized by severe air hunger, hypoxia, jugular venous distension, hyperressonance to percussion on the effected side, and a tracheal shift away from the effected side. The tracheal shift often requires a chest x-ray to appreciate. This is relieved in an emergency by a needle thoracotomy (inserting a needle catheter) into the 2nd intercostal space at the mid-clavicular line, which relieves the pressure in the pleural cavity.
• Thrombosis (Myocardial infarction) - If the patient can be successfully resuscitated, there is a chance that the myocardial infarction can be treated, either with thrombolytic therapy or percutaneous coronary intervention.
• Thromboembolism (Pulmonary embolism) - Usually diagnosed at autopsy. Patients in asystole or pulseless electrical activity have a poor prognosis. If this can be detected early, the patient may receive dopamine, heparin, and thrombolytics.
• Trauma (Hypovolemia) - Reduced blood volume from acute injury or primary damage to the heart or great vessels. Cardiac arrest secondary to trauma, particularly blunt trauma, has a very poor prognosis.

Complete Differential Diagnosis for Sudden Cardiac Death

• Acute aortic insufficiency
• Acute coronary syndrome
• Aortic dissection
• Aortic stenosis
• Arrhythmogenic right ventricular dysplasia
• Brugada syndrome
• Cardiac tamponade
• Cardiomyopathy
• Catecholaminergic polymorphic ventricular tachycardia
• Commotio cordis
• Complete heart block
• Congenital heart disease
• Congestive heart failure
• Coronary artery disease
• Dilated cardiomyopathy
• Hypertrophic cardiomyopathy
• Jervell and Lange-Nielsen syndrome
• Kugel-Stoloff syndrome
• Long QT syndrome, both congenital and acquired
• Mitral valve prolapse
• Myocarditis
• Naxos disease
• Noncompaction Cardiomyopathy
• Papillary muscle rupture
• Prolonged Q-T Interval Syndrome
• Pulmonary embolism
• Romano-Ward syndrome
• Ruptured abdominal aortic aneurysm
• Sick sinus syndrome
• ST Elevation Myocardial Infarction
• Stokes-Adams Syndrome
• Sudden Infant Death Syndrome
• Timothy syndrome
• Uhl anomaly
• Valvular Heart Disease
• Ventricular rupture
• Wolf-Parkinson-White syndrome with rapid conduction

Complete Differential Diagnosis for Sudden Non-Cardiac Death

• 3-methylglutaconic aciduria, type 1
• Alpha-ketoglutarate dehydrogenase deficiency
• Amniotic fluid syndrome
• Arterial dissections with lentiginosis
• Anaphylaxis
• Aneurysm
• Apoplexy
• Appendicitis
• Asphyxia
• Birth injury
• Bleeding excessive
• Childbirth hemorrhage
• Diabetic ketoacidosis - typically from undiagnosed diabetes
• Drug allergy
• Drug overdose
• Encephalitis
• Fetal death
• Flu mainly in the elderly, infants, infirm or chronically ill
• Food allergy
• Gastrointestinal bleeding
• Homicide
• Hyperbilirubinemia transient, familial, neonatal
• Hypercalcemia
• Hypercapnia
• Hyperkalemia
• Hypokalemia
• Hypoxia
• Injury
• Insect bite
• Intracranial hemmorhage
• Marfan syndrome
• Meningitis
• Meningococcal disease
• Motor Vehicle accident
• Myasthenia Gravis
• Neurocysticercosis
• Opioid overdose
• Oxycontin overdose
• Pain killer overdose
• Pickwickian Syndrome
• Poisoning
• Pulmonary embolism
• Retroperitoneal bleed
• Sepsis syndrome
• Shock
• Sleep apnea
• Snake bite
• Status asthmaticus
• Stillbirth
• Stroke
• Subarachnoid hemorrhage
• Sudden Infant Death Syndrome
• Suicide
• Sleeping pill overdose
• Toxic/metabolic disturbances
• Tranquilizer addiction
• Tension pneumothorax
• Toxic/metabolic disturbances
• Thyrotoxicosis
• Toxic shock syndrome
• Transfusion reaction
• Venom

Complete Differential Diagnosis of the Causes of Sudden Death Including Sudden Cardiac Death

3-methylglutaconic aciduria, type 1 Acute aortic insufficiency Acute coronary syndrome Alpha-ketoglutarate dehydrogenase deficiency Amniotic fluid syndrome Amyloid cardiopathy Anaphylaxis Aneurysm Aortic dissection Aortic stenosis Aorto-ventricular tunnel Apoplexy Appendicitis Arrhythmogenic right ventricular dysplasia Arterial dissections with lentiginosis Asphyxia Asymmetric septal hypertrophy Atrial cardiomyopathy with heart block Atrial fibrillation, familial 1 Atrial myxoma, familial Bleeding excessive Brugada syndrome Cardiac tamponade Cardiomyopathy dilated with conduction defect Catecholaminergic polymorphic ventricular tachycardia Childbirth hemorrhage Commotio cordis Complete heart block Congenital heart block Congenital heart disease Congestive heart failure Coronary arteries - congenital malformation Coronary artery disease Diabetic ketoacidosis - typically from undiagnosed diabetes Drug allergy Drug overdose Encephalitis Familial dilated cardiomyopathy Familial hypertrophic cardiomyopathy 1 Flumainly in the elderly, infants, infirm or chronically ill Food allergy Gastrointestinal bleeding Giant cell myocarditis Heart attack Heart failure Homicide Hyperbilirubinemia transient, familial, neonatal Hypercalcemia Hypercapnia Hyperkalemia Hypokalemia Hypoxia Injury Insect bite Intracranial hemmorhage Jervell and Lange-Nielsen syndrome Kugel-Stoloff syndrome

Marfan syndrome Meningitis Meningococcal disease Mitral valve prolapse Multifocal ventricular premature beats Myasthenia gravis Myocarditis Naxos disease Neurocysticercosis Noncompaction Cardiomyopathy Opioid overdose Oxycontin overdose Pain killer overdose Papillary muscle rupture Paroxysmal ventricular fibrillation Pickwickian Syndrome Poisoning Polymorphic catecholergic ventricular tachycardia Prescribed medication addiction Prinzmetal's variant angina Prolonged Q-T Interval Syndrome Pulmonary embolism Retroperitoneal bleed Motor Vehicle accident Romano-Ward syndrome Ruptured abdominal aortic aneurysm Sepsis syndrome Shock Short QT syndrome Sick sinus syndrome Sinus node disease Sleep apnea Sleeping pill overdose Snake bite ST Elevation Myocardial Infarction Status asthmaticus Stillbirth Stokes-Adams Syndrome Stroke Subaortic stenosis - short stature syndrome Subarachnoid hemorrhage Sudden Arrhythmia Death Syndrome Sudden Infant Death Syndrome Suicide Tension pneumothorax Thyrotoxicosis Timothy syndrome Toxic shock syndrome Toxic/metabolic disturbances Tranquilizer addiction Transfusion reaction Uhl anomaly Valvular Heart Disease Venom Ventricular rupture Ventricular tachycardia, catecholaminergic polymorphic, 1 Wolf-Parkinson-White syndrome

Causes of Sudden Death Including Sudden Cardiac Death by Organ System

Cardiovascular	Amyloid cardiopathy, Congestive heart failure, Ventricular rupture,
* Ischemic	Hypoxia, Coronary thrombosis, Coronary vasospasm, Coronary artery aneurysm, Prinzmetal's variant angina ,
* Pericardial	Cardiac tamponade,
* Myocardial	Asymmetric septal hypertrophy , ST Elevation Myocardial Infarction, Dilated cardiomyopathy, Giant cell myocarditis , Hypertrophic cardiomyopathy, Kugel-Stoloff syndrome , Myocardial infarction, Myocarditis, Rupture of the papillary muscles,
* Endocardial/Valvular	Mitral valve prolapse, Valvular Heart Disease,
* Conduction/Arrhythmia	Arrhythmogenic right ventricular cardiomyopathy, Arrhythmogenic right ventricular dysplasia, Brugada syndrome, Complete atrioventricular block, Jervell and Lange-Nielsen Syndrome, Prolonged Q-T Interval Syndrome, Multifocal ventricular premature beats , Naxos disease , Romano-Ward syndrome , Sick sinus syndrome, Short QT syndrome , Sinus node disease, Stokes-Adams Syndrome, Sudden Arrhythmia Death Syndrome, Wolf-Parkinson-White syndrome,
* Vascular	Acute aortic insufficiency, Acute coronary syndrome, Aortic dissection, Aortic stenosis, Aorto-ventricular tunnel, Arteritis, Coronary artery disease, Coronary arteries - congenital malformation , Ruptured abdominal aortic aneurysm,
Congenital/Developmental	Congenital heart disease, Congenital heart block , Congenital Long QT syndrome, Noncompaction Cardiomyopathy, Sudden Infant Death Syndrome, Uhl anomaly
Chemical / poisoning	Snake bite
Dermatologic	No underlying causes
Drug Side Effect	Drug allergy, Drug overdose
Ear Nose Throat	No underlying causes
Endocrine	Catecholaminergic polymorphic ventricular tachycardia, Diabetic ketoacidosis - typically from undiagnosed diabetes, Thyrotoxicosis,
Environmental	Hypothermia,
Gastroenterologic	Appendicitis, Gastrointestinal bleeding, Retroperitoneal bleed,
Genetic	Brugada syndrome, 3-methylglutaconic aciduria, type 1, Familial dilated cardiomyopathy , Familial hypertrophic cardiomyopathy 1, Hyperbilirubinemia transient, familial neonatal, Marfan syndrome , Timothy syndrome
Hematologic	No underlying causes
Iatrogenic	Transfusion reaction
Infectious Disease	Flu mainly in the elderly, infants, infirm or chronically ill, Neurocysticercosis
Musculoskeletal / Ortho	No underlying causes
Neurologic	Apoplexy, Encephalitis, Intracranial hemmorhage, Meningitis, Stroke, Subarachnoid hemorrhage,
Nutritional / Metabolic	3-methylglutaconic aciduria, type 1, Alpha-ketoglutarate dehydrogenase deficiency , Food allergy
Obstetric/Gynecologic	Amniotic fluid syndrome , Childbirth hemorrhage,
Oncologic	Atrial myxoma, familial
Opthalmologic	No underlying causes
Overdose / Toxicity	Opioid overdose , Oxycontin overdose, Pain killer overdose , Sleeping pill overdose
Psychiatric	No underlying causes
Pulmonary	Hypercapnia, Pickwickian Syndrome, Pulmonary embolism, Tension pneumothorax, Status asthmaticus
Renal / Electrolyte	Hypercalcemia, Hypokalemia, Hyperkalemia,
Rheum / Immune / Allergy	Amyloidosis, Anaphylaxis, Myasthenia gravis, Sarcoidosis,
Sexual	No underlying causes
Trauma	Commotio cordis, Homicide, Motor Vehicle accident
Urologic	No underlying causes
Miscellaneous	Shock, Asphyxia, Insect bite Sepsis syndrome, Shock