Methadone Deaths
Deaths related to Methadone have been reported to be on the rise. Reasons include:
… Increased prescribing of the substance by physicians not properly trained in its use.
… Irresponsible and careless use of the substance by patients, despite appropriate prescribing indications, and instructions, by well trained pain management specialists.
… Crack down on the availability of illegal substances, with the unforeseen and subsequent deviation of drug addicts to deceitful procurement of pain medications from well intentioned physicians.
… Drug abuse
… Accidental deaths due to unforeseen emerging circumstances, such as cardiac arrhythmias.
This rise has led to a wave of litigation and professional liability cases. Although it is true that medical malpractice occurs, true malpractice is not as common as the legal system would like you to believe. It is the responsibility of a medical expert witness to carefully evaluate all of the evidence, not just selected pieces of evidence, before rendering an opinion as to whether or not malpractice has occurred. In and by itself, not requesting and carefully evaluating all of the evidence, is reprehensible, irresponsible, unethical, and truly represents professional malpractice, on the part of the expert witness. However, since essentially the legal system protects these individuals, they continue to exploit the system, for monetary gains. Litigation has increased for the following reasons:
… Willingness of unethical ìExpert Witnessesî to provide personal opinions, not based on scientific evidence.
… Willingness of unethical lawyers to exploit a broken system for personal financial gains.
… Misrepresentation of the truth by the media, for the purpose of sensationalism.
… Ignorance and misjudgment on the part of forensic pathologists.
The current
controversy illustrates some universally held, but mistaken, notions about the
process of death investigation in the United States and the United Kingdom.
Many assume that forensic pathology is as evidence based as other branches of
medicine. This assumption is not accurate.
In the course of
caring for living patients, doctors who interpret hospital laboratory tests
know, or can quickly find out, the ìnormalî value for any particular drug. But
most doctors (as well as the general public) would be surprised to learn that
there are few if any ìnormalsî in postmortem
toxicology. Non-circulating blood after death is not the same thing as
circulating blood before death, and evidence that the concepts of normal or
therapeutic drug concentrations can be applied to blood from dead bodies is
severely lacking.
Even in living
bodies, interpretation of a single blood concentration measurement is
impossible without considering route of administration, number of doses taken,
and the amount of drug actually in the body. Such information is almost never
available to investigators, making it impossible to determine the cause of
death solely by comparing a single postmortem drug concentration measurement
with a range of published values, originally derived from measurements made in
living people. With chronic use, tolerance occurs, and tolerance cannot be
measured or estimated after death. Healthy patients enrolled in methadone
maintenance programs, for example, may have blood methadone concentrations in
excess of other, non-tolerant methadone users examined on the autopsy table.2
Similarly, we have long known that blood sampled from the heart of a dead
person who had been on long term digoxin treatment may contain a seemingly
toxic concentration of digoxin when, in fact, the actual blood concentration
immediately before death was the appropriate non-toxic therapeutic
concentration.3
Even if it could be
shown that blood concentrations after death were the same as concentrations at
the time of death, which blood sample should be used?
Drug concentrations are likely to have changed after death.4 For
many drugs, including methadone, concentrations may increase by as much as
10-fold.5 Furthermore, drug concentrations in blood samples from
cadavers are site dependent, higher in some locations and lower in others.6
Should the site yielding the lowest or highest result be used? Or should an
average value for three sites be used? Nobody knows because the process has
never been studied systematically.
If the blood
concentration at the time of death cannot be known with certainty, then how is
it possible to extrapolate the time and amount of drug ingested before death?
The simple answer is that such extrapolations are prone to considerable error
and generally should be viewed as unreliable and not evidence based.7
Despite these limitations, such calculations are frequently and wrongly
produced during court proceedings, even though the problems we outline have
been widely known for many years.
Postmortem
measurements of drug concentration in blood have scant meaning except in the
context of medical history, the sequence and circumstances surrounding death,
and necropsy findings. The paucity of evidence based science, coupled with the
pretence that such science exists in regard to postmortem toxicology, leads to
the abuse of process, almost certainly to the miscarriage of justice, and
possibly even to false perceptions of conspiracy and cover up.
Death investigation
and forensic pathology are also not immune to misinterpretation. Poor or
inadequate death investigation and incomplete or misinterpreted forensic
pathology studies may also result in wrong conclusions. All aspects of the medicolegal
death investigation triadóinvestigation (history), pathology, and laboratory
resultsóare essential and must be evaluated in context with one
another.
Methadone can cause death in one of two ways:
… Overdose
… Toxicity
When a death occurs, on a patient using methadone, it is irresponsible on the part of the forensic pathologist and/or forensic examiner, to give a determination on the cause of death, until the medicolegal death investigation triadóinvestigation (history), pathology, and laboratory results has been fully evaluated. This is especially true when methadone is suspected to be involved. A thorough investigation into the practices of procurement and use/abuse of methadone is essential to arrive at the proper designation of the cause of death. The following checklists should be used to investigate the case prior to determining if such death was as a consequence of the use of this substance.
History Checklist:
1. Immediately obtain the following information:
__ a. Patientís prior medical history from the primary care physician.
__ i. History of alcoholism, alcohol abuse or misuse.
__ ii. History of substance abuse or misuse.
__ iii. History of non-compliance with medical orders.
__ iv. List of other physicians involved in the patientís care.
__ b. Patientís medication history from all prescribing physicians.
__ i. Investigate for patterns of ìDoctor Shoppingî. (More than one physician prescribing controlled substances).
__ c. Pharmacy printouts from all pharmacies used in the past 24 months.
__ i. Investigate use of multiple pharmacies. Use medical records to find pharmacies where prescriptions may have been called into. Also call pharmacies around the patientís residence, and inquire about prescriptions filled at their location by the patient in question.
__ ii. Investigate possible red flag patterns, such as using medical insurance to pay in some pharmacies, and cash in others. This is sometimes done by patients in an effort to hide control substance acquisition from insurance company monitoring.
__ iii. Use pharmacy records to uncover a complete list of prescribing physicians. Substance abusers will hide from their physicians that they are seeing other prescribers, in order to obtain multiple prescriptions of controlled substances.
__ d. Request from the pharmacy, the time and date of the last methadone refill.
__ e. All medications and medication bottles available to the patient. This includes medications and medication bottles from family members or friends sharing the same household. Request this from the police. Use bottles to get information about the pharmacies frequented by the patient and the family, as well as all prescribing physicians.
__ f. Do and document a complete pill count.
2. Notify the following practitioners:
__ a. Primary care physician
__ b. All prescribing physicians
3. Request from the above physicians the following information:
__ a. All medication records.
__ b. Medical History
__ i. History of alcohol use or abuse
__ ii. History of substance abuse
__ iii. Last drug testing
__ iv. History of cirrhosis of the liver
__ v. Last liver function tests
__ vi. History of hypothyroidism
__ vii. History of hypokalemia or hypomagnesemia
__ viii. Family history of sudden death
__ ix. History of cardiac arrhythmias or emergency room visits for chest pains or palpitations
__ x. History of cardiac catheterizations (negative results may rule out atherosclerotic coronary artery disease, but may suggest dysrhythmias)
__ xi. History of psychiatric disorders
__ xii. History of Gout or kidney stones
__ xiii. History of heartburn or GERD
__ c. Medication History
__ i. MAO inhibitors
__ ii. narcotic analgesics
__ iii. general anesthetics
__ iv. Phenothiazines
__ v. Tranquilizers
__ vi. sedative-hypnotics
__ vii. tricyclic antidepressants
__ viii. Alcohol, ethanol (wine, beer, whiskey, etc.)
__ ix. Barbiturates: Butabarbital sodium, mephobarbital, phenobarbital, pentobarbital, secobarbital
__ x. Carbamazepine
__ xi. Phenytoin
__ xii. Rifampin
__ xiii. urinary acidifiers, ascorbic acid
__ xiv. treatment of depression and anxiety
__ xv. H2 receptor antagonist for the treatment of gastric and duodenal ulcers, and gastric reflux disease
__ xvi. Diazepam
__ xvii. serotonin reuptake inhibitor for treatment of depression and compulsive disorders
__ xviii. Ketoconazole
__ xix. urinary alkalinizers (treatment of kidney stones, gout therapy)( Bicitra, Polycitra)
Pathology Checklist:
1. Look for signs of chronic alcohol intake:
__ a. Cirrhosis of the liver
__ b. Fatty liver
__ c. Aseptic necrosis of the hips
__ d. Little or no atherosclerosis
2. If patient was taking medication due to pain, investigate area of complaints to confirm true history of disease.
3. Examine gastric content
Laboratory Checklist:
1. Perform the following laboratory test:
__ a. Send a sample of the methadone pills for quantitative and qualitative analysis.
__ b. Obtain a clean catch urine sample and send quantitative and qualitative drug screening. Request testing for:
__ i. Tramadol
__ ii. Opioids (methadone, morphine, Fentanil, Oxycodone, Oxymorphone, Hydrocodone, and metabolites)
__ iii. Benzodiazepines
__ iv. Cocaine
__ v. Cannabinoids
__ vi. Amphetamines
__ vii. Antipsychotics
__ viii. Antidepressants
__ ix. Ethanol/alcohol
__ x. Also test for ph and specific gravity
__ b. Test all blood and fluid samples for:
__ i. Tramadol
__ ii. Opioids (methadone, morphine, Fentanil, Oxycodone, Oxymorphone, Hydrocodone, and metabolites)
__ iii. Benzodiazepines
__ iv. Cocaine
__ v. Cannabinoids
__ vi. Amphetamines
__ vii. Antipsychotics
__ viii. Antidepressants
__ ix. Ethanol/alcohol
__ c. Obtain blood samples from the heart and analyze for quantitative methadone levels.
__ d. Obtain and analyze vitreous humor for quantitative methadone levels.
__ e. Obtain cerebral blood sample and analyze for quantitative methadone levels.
__ f. Liver sampling is not an appropriate sample for methadone testing since the drug is normally stored in the liver, therefore the concentration will normally be significantly higher than plasma. Liver sampling should never be used to suggest overmedication. Fatty livers will actually store even more concentrations, due to the lipophilic nature of methadone.
References
1. Olaf Drummer, adjunct professor, Victorian Institute of Forensic
Medicine, 57-83 Kavanagh Street, Southbank, Victoria
3006, Australia.Ý A. Robert W. Forrest, professor
of forensic toxicology, University of Sheffield, Sheffield S3 7ES. Bruce
Goldberger, associate professor, Department of Pathology, Immunology and
Laboratory Medicine, University of Florida College of Medicine, PO Box 100275,
Gainesville, FL 32610-0275, USA. Steven B Karch, assistant
medical examiner, PO Box 5139, Berkeley, California 94705-0139, USA.
International Toxicology Advisory Group. Forensic science in the dock. -
Postmortem measurements of drug concentration in blood have little meaning. ÝBMJ.
2004 September 18; 329(7467): 636ñ637.Ý doi: 10.1136/bmj.329.7467.636.
2. Karch SB, Stephens BG. Toxicology and pathology of deaths related to methadone: retrospective review. West J Med 2000;172: 11-4. [PubMed