Abstract
The primary responsibility of the forensic pathologist is to determine the cause of death. Inclusion of the mechanism of death is not required on death certificates, and therefore, forensic pathologists often (appropriately) do not include mechanisms in cause of death statements. When determining the cause of death; however, it is nonetheless important to consider the responsible physiologic mechanism. If the mechanism of death is not taken into account, an erroneous cause of death may be attributed. This review article will highlight examples of the types of cases in which this may occur.
Introduction
The most basic mandate for forensic pathologists is to determine the cause of death. Since the focus is on determining cause of death, the mechanism by which death occurs is occasionally overlooked. This is the opposite perspective of that held by clinicians, who are often more interested specifically in the mechanism of death. In hospital autopsies, the cause of death is often already known; and when clinicians ask how their patient died, they are usually thinking mechanistically. Clinicians tend to be more focused on the “ground view”, whereas forensic pathologists are more concerned with the “big picture”. Such a dichotomy can lead to dissatisfaction on the part of clinicians reviewing autopsy reports prepared by forensic pathologists.
Forensic pathologists generally do not include a mechanism of death when certifying a death, unless it is followed by a proximate cause on the death certificate. For example, it is inappropriate to certify a cause of death simply as “asphyxia”, as this is a mechanism of death and not a cause (1). Many pathologists limit what they write in the first line (a) of Part I of the death certificate; for example, “hanging”. Other pathologists might list the cause of death statement as “asphyxia” (in the first line) due to “hanging” in the second line (b) of Part I. Another variation in this example is if the person had survived for a few days in the hospital; the pathologist might certify the cause of death as “hypoxic-ischemic encephalopathy” due to “hanging”. Each of these variations is medically correct because although “asphyxia” and “hypoxic-ischemic encephalopathy” are both specific mechanisms of death, they were ultimately followed by the underlying cause of death on the death certificate.
While there is no requirement to record the mechanism of death on a death certificate, and in fact it is discouraged (1), it must be considered when determining the cause of death. On the surface, a given cause of death might seem reasonable, until one looks more closely at the necessary mechanism of that proposed cause. When the mechanism of death is considered, the cause of death determination may come into question.
In our pursuit of the ‘big picture’, forensic pathologists are often categorized (colloquially) as “lumpers”, in comparison with the “splitters” thought to populate other medical specialties. As lumpers we often try to be as inclusive as possible in contributing various factors to death. It is reasonable to include two factors (or causes) together, provided their mechanisms of action are not incompatible. For example, it is reasonable to include both lung cancer and pneumonia in a cause of death statement because the mechanisms by which they can contribute to death can coexist. It is not appropriate to include multiple causes of death, however, if their mechanisms cannot coexist.
Discussion
The following vignettes are hypothetical case examples which illustrate the importance of considering the mechanism of death when determining the cause of death. The categories to be discussed are 1) mechanism of drug action, 2) mechanism of injury, and 3) things that are not mechanisms at all, but rather, factors that contribute only to circumstances leading to death.
Mechanism of Drug Action: Example 1—Acetaminophen
A 45-year-old man with no significant medical history and no history of recent complaints was taken to the emergency department after being found unresponsive at home. He exhibited faint vital signs but was unable to be resuscitated. No antemortem laboratory analyses were performed. His wife indicated that he did not use illicit drugs and was not prescribed any medication. She further stated that he told her that he was going to take some acetaminophen. Autopsy examination was grossly and microscopically unremarkable. Toxicology testing revealed only acetaminophen. Based on the estimated time the drug was taken and the concentration identified, the Rumack-Matthew nomogram (2) indicated probable hepatotoxicity. The cause of death was certified as “toxic effects of acetaminophen”, with an accidental manner of death.
Although consideration was given to the potential toxicity of acetaminophen by consulting the Rumack-Matthew nomogram, it is not appropriate to invoke acetaminophen toxicity in a case such as this one. The mechanism of action of acetaminophen toxicity has been elucidated in great detail (reviewed in (3)). Acetaminophen is metabolized by cytochrome P-450 to N-acetyl-p-benzoquinone imine (NAPQI). NAPQI then depletes intracellular glutathione stores, the end result of which is fulminant liver necrosis with hepatic failure. In the case example presented, liver necrosis was absent on both gross and microscopic examination. As fulminant hepatic necrosis is the only known mechanism for acetaminophen-induced lethality, it is not possible that acetaminophen was responsible for the death in this case and if another explanation is not identified, the cause of death is best left undetermined. Sudden deaths with high concentrations of acetaminophen, but without liver damage have been reported, and it has been suggested that another mechanism may be at play (4). There is currently; however, no scientific evidence to support this hypothesis. Invoking acetaminophen toxicity as a cause of death in a case without liver necrosis is not appropriate because it is not mechanistically possible given the current state of the knowledge regarding the drug's mechanism of action.
One of the principles of death certification is that if there is only one potential cause of death, and there is no competing potential cause of death, then the available explanation should be considered to be the cause of death. This is more colloquially described as “going with what you have”. Since no competing cause of death could be identified in the above example, some forensic pathologists might consider acetaminophen toxicity to be an appropriate label. This approach is inappropriate, however, if the only potential cause of death is not mechanistically possible.
Mechanism of Drug Action: Example 2—Drugs and Natural Disease
A 45-year-old man was found dead at home. His medical history was significant only for hypertension; antihypertensive medications were found in his home. Autopsy revealed cardiac hypertrophy (heart weight = 560 g), with concentric left ventricular hypertrophy. Microscopic examination revealed cardiomyocyte hypertrophy, focal interstitial myocardial fibrosis, and renal hyaline arteriolosclerosis. Toxicology testing revealed the presence of cocaine and benzoylecgonine in postmortem blood. The cause of death was certified as “hypertensive cardiovascular disease” in Part I, with “toxic effects of cocaine” listed in Part II. The manner was certified as accident.
This certification is appropriate because the mechanisms of each of the listed causes are compatible. Hypertensive hearts are at an increased risk for arrhythmias, and it is well known that cocaine is arrhythmogenic as well (5, 6). Two independent causes can be contributing to death through one common mechanism.
But not all combinations of natural disease and drugs should be co-contributed to death. For example, cocaine might be detected in a decedent who is found to have fulminant bacterial meningitis. Although it is recommended that comorbidities be listed on the death certificate (1), it should be emphasized that this is not intended to create an exhaustive list of every disease and condition identified; but rather, that the death certificate be limited to those conditions that are felt to be contributory to the death. To list both the meningitis and the toxic effects of cocaine simply because both conditions were present in the same decedent is to ignore the pathophysiologic mechanisms by which these two entities could cause death. The mechanisms of death for each of these causes have nothing to do with one another and they would not be additive or synergistic. The meningitis might cause death, for example, by disseminated intravascular coagulation. For cocaine to cause the death, it would have to cause a lethal cardiac arrhythmia at a specific moment in time, and this would not be influenced by the presence of meningitis. Listing them both would suggest that the two independent mechanisms (and thus causes) were simultaneously at play (a proverbial “two-fer”) when in fact is much more likely that only one of the two potential causes actually caused death. In other deaths, particularly with chronic diseases, independent diseases with independent mechanisms could both be reasonably listed on the death certificate. For example, a patient with end-stage emphysema and end-stage ischemic heart disease could legitimately have both disease processes, with independent mechanisms, contributing to death simultaneously.
Mechanism of Injury
A vehicle was traveling at a high rate of speed. The driver lost control and overcorrected in a turn, collided with and flipped over a retaining wall, and came to rest submerged in a pond. After the vehicle was extracted from the water, the decedent was noted to be safety-belted into the driver's seat. The external examination revealed wet clothing and wrinkling of the skin of the palms and soles. There were also generalized abrasions, contusions, and lacerations. The internal examination showed several fractured ribs, lung lacerations, and an atlanto-occipital dislocation with associated high cervical cord contusion. The death was certified as “blunt trauma”, with “drowning” listed in Part II (other significant conditions contributing to death) of the death certificate.
In this case, the mechanism of the blunt force injury was not taken into account. The atlantooccipital dislocation is an immediately lethal injury. Given this scenario, it is not possible for drowning to contribute to death because the driver would have been dead immediately upon impact, perhaps even before the vehicle entered the water. The fact that the body was recovered from water is a mere coincidence in this case. It would be inappropriate to list drowning as a contributing factor; the cause of death statement should be limited to blunt trauma.
With severe but not necessarily immediately lethal injuries, it is certainly possible that if the driver were not immediately killed, that a component of drowning after becoming submerged may be a significant factor contributing to death. This combination of the two causes of death is reasonable because both could be contributing to death simultaneously and their mechanisms can coexist. In the example given, if an atlantoocciptal dislocation (or other immediatlely lethal injury) were not present, blunt trauma and drowning could reasonably contribute to death simultaneously.
Factor Contributing to Circumstance Rather than Mechanism
A 21-year-old man was on a recreational boat on a lake, consuming ethanol with his friends, who later described him as being moderately intoxicated. He was playing catch with a beach ball, lost his balance, and fell off the side of the boat and into the water. Witnesses saw him go under water without resurfacing. They searched for him in vain; his body was recovered from the water a few hours later. An autopsy revealed the absence of injury and natural disease, and showed only edematous lungs and froth within the airways. Postmortem toxicology testing showed blood and vitreous ethanol concentrations of 0.15 mg/dL and 0.12 mg/dL, respectively. The death was certified as “drowning”, with “acute ethanol intoxication” listed in Part II (other significant conditions contributing to death).
In this example the mechanism of action of ethanol was not taken into account. Ethanol kills by respiratory depression, with intoxicated individuals progressing to a coma and then death. Prior to the fall, the history was that the decedent was partying with his friends. He was conscious and engaged in physical activity. This history, coupled with the relatively low ethanol concentrations is incompatible with an ethanol-induced respiratory depression and death. While ethanol toxicity is certainly capable of being a cause of death, it was not contributing mechanistically to death in this case. The fact that the decedent was intoxicated surely contributed to the circumstance of falling into the water due to ethanol's effects on balance and coordination. Put another way, ethanol ingestion and intoxication was a risk factor for drowning. Although ethanol also likely interfered with the decedent's ability to swim to safety, it played no mechanistic role in the dying process. As such, it should not be invoked as a contributing cause of death.
This is not unlike cases encountered every day in which drivers of motor vehicles experience lethal collisions while intoxicated: the ethanol is likely a contributing factor affecting the drivers’ judgment and coordination, but does not mechanistically cause the death. Therefore, ethanol should not be included in the cause of death statement. Similarly, if a depressed person becomes intoxicated and shoots himself in the head, the ethanol can certainly be seen as a contributory factor to the circumstances leading to the death (loss of inhibitions and poor judgment), but of course is not a causative factor in the death itself. Again, in such a situation, ethanol intoxication is a risk factor for self-harm behaviors. Put another way, ethanol is no more a contributing cause of death than the underlying depression. In each of these examples, the person may have gotten into a risky situation because of the intoxicating effects of ethanol, but their deaths were not caused mechanistically by the drug.
Conclusion
Although listing a mechanism of death in a cause of death statement is not required, the mechanism associated with the proffered cause of death must be compatible with the circumstances and findings in the case. In the example involving acetaminophen, a potential cause of death existed, but the autopsy ruled out the only known (lethal) mechanism of action of the drug. Other cases involving drugs and natural disease must have mechanisms that are compatible in order to contribute both to the cause of death. Similarly, invoking multiple traumatic causes of death, such as in the example of the driver with blunt force injuries whose car entered the water, is only appropriate if the their mechanisms can coexist. Finally, certain factors may contribute to the circumstances surrounding the death, but are not themselves either mechanisms or causes of death in certain situations. These ‘risk factors’ are reasonably included in the opinion section of the autopsy report as contributory to the situation; however, unless such factors directly contribute to death mechanistically, they should not be included as part of the cause of death statement.
Footnotes
The author, reviewers, editors and publication staff do not report any relevant conflicts of interest.