Drug overdose deaths and toxicology tests: Let’s talk

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Case No. 1: Opioid-related death occurring outside hospital setting. A 57-year-old male with a known history of substance abuse was found dead in his bed. A medical examiner autopsy was performed. Internal examination revealed pulmonary emphysema and mild atherosclerosis. The combined lung weight was 2,040 grams. A postmortem urine drug screen was positive for methamphetamine, alprazolam, fentanyl, norfentanyl, morphine, 6-monoacetylmorphine (6-MAM), codeine, and hydromorphone. Toxicology tests performed on postmortem femoral blood revealed the following: alprazolam: 13.7 ng/mL; fentanyl: 22.4 ng/mL; morphine: 15.1 ng/mL; acetylfentanyl: 136 pg/mL. The cause of death was ruled “combined toxic effects of fentanyl, acetylfentanyl, heroin, and alprazolam.”

The markedly heavy lung weights in this case represent a classic finding in opiate-related deaths. The urine toxicology results provide insight into why it is important to use blood levels (rather than urine levels) when attempting to determine which drugs are involved in a death. For instance, had urine results alone been used, methamphetamine would likely have been considered a contributing factor in the death.

Case No. 2: Opioid-related death occurring acutely within hospital setting. A 26-year-old female with a history of polysubstance abuse was found unresponsive and emergently transported to the emergency department. She had a history of multiple intentional and unintentional drug overdoses, suicidal ideation, depression, and anxiety. A urine drug screen in the ED was positive for opiates, cocaine, and amphetamines. She was admitted to the intensive care unit, diagnosed with anoxic brain injury, and pronounced brain dead two days later. Following organ and tissue donation, her body was transported to the medical examiner for autopsy. Autopsy disclosed no significant findings other than changes consistent with anoxic encephalopathy. Autopsy samples were not tested. Admission hospital blood samples were positive for acetylfentanyl, at a level of 1,121 pg/mL. The cause of death was ruled as “complications of acetylfentanyl toxicity.”

This case highlights the fact that admission hospital blood samples can be essential in identifying the drug(s) responsible for death. In addition, the case is a good example of situations in which designer opioids can be considered the sole cause of death.

Case No. 3: Opioid-related death following prolonged hospital admission (blood sample available but quantity insufficient for complete testing). A 29-year-old male with a history of heroin abuse was found unresponsive and transported to the ED via ambulance. A urine drug screen performed on admission was positive for opioids and marijuana. He was admitted to the ICU but subsequently diagnosed with anoxic encephalopathy and died three days later. His body was sent for medical examiner autopsy, which revealed slight cardiomegaly and mild coronary artery atherosclerosis. Admission and subsequent hospital blood samples were retained and tested, but the quantity of samples was insufficient to perform complete toxicologic testing. Autopsy blood samples were not tested due to the several day hospital stay. The cause of death was ruled “toxic effects of opioids” with a contributing cause of “cardiomegaly.”

This case represents an example of a situation in which hospital blood samples were still available for testing, but insufficient sample quantities resulted in the inability to determine a definitive cause of death. Had a higher volume of blood been available, testing could have provided definitive results. Additionally, if blood had been collected in a gray-top tube, the testing would have been even more suitable for toxicology testing.

Case No. 4: Opioid-related death following prolonged hospital admission (no blood sample available). A 30-year-old woman with a known history of drug abuse and depression was found with altered mental status and an empty Norco pill bottle on her lap. Emergency medical services administered Narcan, after which there was noted respiratory improvement but the patient remained obtunded. She was transported to the emergency department, where a urine drug screen was positive for opiates, amphetamines, cocaine, and THC. She was admitted to the ICU with a diagnosis of suspected drug overdose. After a 20-day stay in the ICU, which was complicated by aspiration pneumonia and acute respiratory distress syndrome (ARDS), the patient died. The case was referred to the medical examiner. No hospital admission blood was available for testing. Autopsy disclosed diffuse alveolar damage, consistent with the clinical impression of ARDS. The cause of death was certified as “complications related to a drug overdose.”

This is an example of a classic case where a final, definitive answer regarding which drug(s) was/were responsible for death could not be determined. Without knowledge of the specific drugs present within the patient’s blood on admission, there is no possible way to provide such valuable information on the death certificate. Although several drugs were evident in the urine on admission, relying on urine test results is not acceptable and allowed the certifier only to provide very general terms about the cause of death.

Case No. 5: Opioid-related death following prolonged hospital admission (blood sample collected in gray-top tube available for testing). A 52-year-old woman was at home with her family when she began to have difficulty breathing and became unresponsive. Paramedics intubated her and transported her to the local hospital where resuscitative efforts continued. An admission urine drug screen was negative. An admission tube of blood was collected in a gray-top tube and stored in the blood bank, as per established hospital protocol. Ultimately the patient remained on a ventilator for seven days before being pronounced dead. Further questioning revealed that she had purchased “Percocet” from an unknown individual the same day she was admitted to the hospital. Due to this history, and a known cluster of overdoses within a similar geographic area and time frame, the body was transported to the medical examiner for autopsy. The hospital admission blood sample was requisitioned and submitted by the ME for toxicologic analysis. Autopsy revealed acute (presumed ventilator-associated) bronchopneumonia. Testing performed on postmortem blood revealed only hospital-administered therapeutic drugs. The admission blood, however, was positive for cyclopropyl fentanyl and U-47700. The cause of death was certified as “acute intoxication of cyclopropyl fentanyl and U-47700.”

This last case is an example of a situation in which the hospital, laboratory, and ME/C had previously established a mutually agreed upon protocol, such that all hospital admissions for suspected overdose included collection of an admission blood sample, retained in a sodium-fluoride (gray-top) tube, with the specimen stored for the patient’s entire hospital stay. The benefits of such a protocol are twofold: Admission blood remains available for ME/C use should the patient die, even if the survival time exceeds the usual length of time that lab blood samples are retained, and the blood sample for subsequent ME/C testing is collected in a gray-top tube, which is the preferred sample for toxicology testing.

Conclusions. Although practices and protocols are likely to vary from hospital to hospital and from jurisdiction to jurisdiction, the following general recommendations may be applied to any hospital laboratory regarding the collection of blood samples for potential forensic testing in suspected drug overdose cases. It is unlikely that every jurisdiction and hospital will be able to employ the same protocols to assist ME/C offices in providing the most useful and correct information for death certification purposes in opiate and other drug-related deaths. However, several options exist. When considering how hospital laboratories can assist in these cases, the following options should be considered, either separately or in combination:

• Lengthen the amount of time all blood samples are retained in the laboratory prior to disposal.
• Selectively save blood samples from patients admitted for suspected drug overdoses, and do not dispose until patients are discharged (or die, at which time samples are to be sent to the ME/C).
• Implement a policy wherein a gray-top tube of blood is collected in all suspected drug overdose admissions, with samples retained as indicated in the preceding second option.
• Notify law enforcement of admissions for drug overdose, with subsequent court-ordered blood draws for drug quantification (similar to cases of alleged drunk driving, where law enforcement obtains court order to obtain blood samples).

Identification of the appropriate tests to be ordered, proper specimen collection, accurate laboratory testing, timely reporting of test results, and the interpretation of test results are each essential parameters in diagnosis, prognosis, and providing guidance in health care decisions. However, communication regarding these parameters within the various health care groups and across multiple disciplines is lacking, thus stifling access to a collection of the best available information that might be resourced to develop effective health care strategies. In our quest to provide comprehensive patient-centric health care services, a collaboration among forensic and hospital pathologists, hospital clinicians, and laboratorians can improve death certification accuracy, ensure more focused monitoring and publication of drug overdose death trends, and ultimately better prevent future overdose deaths.

This article was written on behalf of the CAP Forensic Pathology Committee, of which Dr. Prahlow is vice chair and Dr. Brooks is a member. Dr. Brooks, a forensic pathologist, is associate professor of pathology and residency program director, Department of Pathology and Laboratory Medicine, University of Wisconsin Hospital and Clinics, Madison. Dr. Prahlow, a forensic pathologist, is deputy medical examiner, professor of pathology, and vice chair of the Department of Pathology, and Dr. Jones, a forensic toxicologist, is associate professor, Department of Biomedical Sciences—both at Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.