When “Natural Death” May Not Tell the Whole Story
Consider the following case. A woman is hospitalized for pneumonia. Her physician tells the family that the antibiotic treatment has been successful and that she is expected to be discharged within two days.
When the family returns to the hospital, however, they learn that her condition has deteriorated significantly. That evening, she is transferred to the intensive care unit. Early the following morning, they are informed that she has died and that the treating physician cannot explain why.
The death certificate later records the manner of death as “natural.”
During her hospitalization, she had been receiving as many as 15 medications per day. Her family therefore asked SCHOLZ DataBank to examine whether adverse drug effects or drug-drug interactions may have contributed to the unexpected fatal outcome.
A plausible medication-related scenario
An analysis using the SCHOLZ DataBank Adverse Drug Risk Control Panel and the MDDI Calculator identified a plausible chain of events involving:
- Acute kidney injury (AKI)
- Potentially toxic multiple drug-drug interactions (MDDI)
- Severe bleeding resulting in hemopericardium
- Cardiac arrest as the final event
The findings suggested that the patient’s medications may have produced serious multiple drug-drug interactions, potentially increasing the plasma level of one drug to a toxic range. Acute kidney injury may have further increased the drug exposure. Together, these effects provided a plausible medication-related explanation for the fatal outcome.
As clinical decision support applications, the SCHOLZ DataBank tools help uncover clinically significant medication risks and provide medical, pharmacological, and legal experts with a foundation for further investigation.
Why polypharmacy requires closer examination
Patients with multiple medical conditions frequently receive medications from several physicians and specialists. When many drugs are taken simultaneously, reviewing each medication separately may not reveal the combined risks of the complete medication regimen.
A comprehensive analysis should consider:
- Drug-drug interactions, including multiple drug-drug interactions (MDDI)
- Overlapping and cumulative adverse effects
- Contraindications associated with diseases and individual risk factors
- Dosage and duration of treatment
- Kidney and liver function
- Age, sex, and pharmacogenomics
- The cumulative risk of the complete medication regimen
A death classified as natural does not necessarily exclude medications as contributing factors. This may be particularly relevant when a patient dies unexpectedly while receiving extensive polypharmacy and no clear clinical explanation is available.
The wider impact is substantial. A 2018 study estimated that morbidity and mortality associated with nonoptimized prescription medication therapy cost the United States approximately $528.4 billion in 2016.¹
Supporting medication-related investigations
SCHOLZ DataBank can support complex medication reviews undertaken by:
- Families seeking greater clarity about an unexpected death
- Medical malpractice and wrongful death attorneys
- Pharmacology and clinical pharmacology expert witnesses
- Physicians, forensic experts, and pathologists
- Hospitals, insurers, and patient safety organizations
- Pharmaceutical and pharmacovigilance professionals
When a serious or fatal outcome cannot be adequately explained and the patient was receiving multiple medications, a structured medication risk analysis may provide important additional insight.
If you are investigating an unexpected adverse event, suspected medication-related injury, or death involving polypharmacy, please contact SCHOLZ DataBank to discuss how our clinical decision support applications may assist your review.
¹ Watanabe JH, McInnis T, Hirsch JD. Cost of Prescription Drug-Related Morbidity and Mortality. Annals of Pharmacotherapy. 2018;52(9):829–837. View on PubMed.