ERIC G. COMSTOCK, M.D., P.A.
Medical toxicology consultation on the above-captioned matter is requested by the parties defendant.
This litigation arises as a result of the death of (Female) on February 27th, at a hospital. The parties plaintiff allege that her death occurred as a consequence of breach of standard of care by the defendants who provided treatment to (Female) for drug addiction.
Records reflect that the patient was admitted to Methadone maintenance treatment on February 24th, after determination of her history of opiate dependence as documented in the medical records. She was qualified under Federal and State regulations to receive Methadone maintenance treatment. Thirty milligrams (30 mg) of Methadone was administered on February 24th , and after appropriate observation by the clinical staff, an additional 10 milligrams of Methadone was administered because of persistence of signs and symptoms of withdrawal distress, providing a total of 40 milligrams of Methadone on the first day of treatment.
On February 25th, 26th, and 27th, the patient was observed by the clinical staff and reported inadequate control of her withdrawal discomfort so on each day, an additional
10 milligrams were administered. The pattern of Methadone administration was consistent with the universally recognized procedure known as titration, whereby the dose is gradually increased until the withdrawal discomfort sustained by the patient is controlled. This titration procedure is required to determine appropriate dose for Methadone maintenance treatment.
On February 27th, the patient reported that the medication was not holding her for a full day so she had supplemented with Xanax on February 26th. On February 27th, the patient was administered 70 milligrams, taken under the direct observation of the clinic staff.
At 3:07 p.m. on February 27th, the patient was pronounced dead at the hospital.
A postmortem examination was performed on February 28th, starting at 7:00 a.m., at the County Morgue. There was evidence of medical intervention prior to declaration of death. No anatomical cause of death was identified. Toxicology analyses were performed by a toxicology Laboratory in Texas. Urine screen revealed the presence of benzodiazepines, tricyclic antidepressants and Methadone. The analyses on blood revealed the presence of Methadone quantitated by gas chromatography/mass spectrometry (GC/MS) as 1.5 milligrams per liter of blood (mg/L). The serum equivalent was 2.0 mg/L. The blood specimen was also positive for Methadone metabolite.
As a consequence of postmortem laboratory evaluation, the Medical Examiner determined the cause of death to be Methadone overdose, with the manner of death noted as an accident. The postmortem examination failed to reveal any abnormality of the liver on gross examination.
The plaintiffs allege that death occurred as a consequence of the Methadone administered to the patient in the course of her treatment provided at the methadone maintenance treatment program (MMTP).
In developing an opinion concerning the death of this patient, I have reviewed several thousand pages of medical records, documenting treatment received by the patient prior to her admission to the MMTP. I have reviewed the records documenting the treatment provided to the patient by the MMTP. I have reviewed the depositions of (Physician), and ex-husband of the patient. I have reviewed the medical records concerning the emergency medical care provided at the hospital in the course of a resuscitation attempt on this patient. I have reviewed the reports of (Plaintiff expert, Ph.D.) and (Plaintiff expert, M.D.)
It is my opinion in reasonable medical probability that the patient died as a result of an overdose of Methadone as a consequence of the patient supplementing the Methadone provided by the MMTP by self-administration of additional Methadone obtained in the community. The patient exceeded her tolerance for opiate drugs either accidentally or as a result of a self-destructive behavior.
In reasonable medical probability, the pharmacology and pharmacokinetics of Methadone eliminate any possibility that the concentrations of Methadone present in the blood of this patient at the time of the postmortem examination could be achieved as a result of the Methadone administered at the Methadone maintenance treatment program.
Review of the medical records generated by the MMTP fails to reveal any breach of standard of care provided this patient either by Methadone maintenance treatment or by the prescribing physician.
The general qualifications upon which I base my opinion are set forth in my Curriculum vitae, attached. My qualifications relevant to my opinion in this specific case consist of treatment of more than 1,000 patients in emergency departments and intensive care units for acute poisoning, more than 80% of which were the result of drug overdose; provision of inpatient drug treatment and withdrawal as Medical Director of the inpatient detoxification program in Harris County, Texas, under Judge Elliott, in which capacity the concept of titration to determine tolerance to opiate drugs was developed and published in Texas Medicine (see reference); the concept of titration to determine tolerance and consequently addiction or dependence on prescription drugs was further applied under a grant from the National Institute on Drug Abuse (NIDA) polydrug abuse research and treatment program. A research and treatment program was established that provided research and treatment of 212 polydrug-using patients; consultation on 1200
consecutive admission to Ben Taub Hospital in Houston, Texas, under grant supported by NIDA, the Texas Program on Drug Abuse, and Texas Council on Alcoholism; the development and testing of a national program using emergency department records for early detection of drug abuse trends in the United States sponsored by the Bureau of Narcotics and Dangerous Drugs; research on the relationship between drugs and death presented as a guest of the National Center for Studies on Suicide Prevention symposium; provision of Methadone maintenance treatment 1976 to 1980, under contract with the Texas Program on Drug Abuse; and continued in 1980 after funding by the State program was discontinued. Subsequently, I have supervised the provision of Methadone maintenance treatment over a period of 30 years, providing such services for in excess of
10,000 patients. My experience has assisted in establishing the standard of care for Methadone maintenance treatment in the United States. Currently, as Medical Director of Toxicology Associates, I supervise a population on an average of 600 to 650 patients in treatment. Prior to medical school, I had four years of graduate work at the University of California Berkeley with course and laboratory experience in biological research, analytical chemistry, experimental pathology, and public health leading to a Master’s degree in microbiology.
In his preliminary report of November 25th, (Plaintiff expert, Ph.D.), paragraph 2 on page 3, noted that “Her death was caused by Methadone toxicity. This ruling from the postmortem does not imply Methadone overdose.” This statement is correct insofar as the concentration of Methadone present in the circulating blood at time of death does not
establish the mechanism by which the elevated concentrations occurred. One possible mechanism is the accumulation of Methadone, when given in ordinary doses, which
increase gradually as a result of the inability of the liver to function properly in the metabolism of Methadone to its less active or inactive derivative. It is noted that amphetamine taken on a chronic basis leads to liver damage and the presence of the liver damage is sufficiently severe to impair the dispositional metabolism of Methadone.
It is noted that “special laboratory test panels must be ordered to assess liver function.” Reference to the admission laboratory work performed on this patient on February 24th, and reported on February 25th, included the two most commonly used parameters for detection of liver malfunction based on blood tests. These included ALT, reported as 41 (with a reference range of 0-54), which is a normal value; and AST which was reported as 35 (with normal range of 10-40), which is also a normal value. At the same time, a test for Hepatitis B was performed and was negative. Consequently, the appropriate procedures were performed on the admission of this patient to assess the presence of liver damage and none was demonstrated.
Additionally, on review of the extensive medical records, none of the clinical conditions or laboratory tests reported support the presence of either acute or chronic liver injury of a type that would change the pharmacokinetics of Methadone.
The discussion of acetaminophen by Baselt, 2004, the reference relied upon by (Plaintiff expert, M.D.), does not even discuss the problem of chronic acetaminophen toxicity but rather limits the discussion to the acute phase.
Goldfrank, 6th Edition, discusses risk after repeated or chronic acetaminophen overdose from the position that the occurrence of such is extremely rare and is subject to uncertainty as to whether it exists. Further, the general overview is one that supports that chronic hepatic compromise, when it does occur, almost always is preceded by episodes of acute hepatic compromise. None of these occurrences have been noted in the extensive premortem medical records of the current patient.
If impaired dispositional metabolism were the consequence of acute liver impairment at the time of the patient’s admission to the Methadone maintenance program, the liver enzymes would have been in the order of several hundred to even thousand units over the
expected normal range. In reasonable medical probability, pharmacokinetic dysfunction to account for the concentration of Methadone in this patient’s blood at the time of death is so remote as to be extremely improbable and has no support in the factual records.
It is further stated “This toxic component potentiates opiate effect.” There is no evidence whatsoever that the unidentified toxic component present as a consequence of impaired dispositional metabolism of acetaminophen has any effect on the pharmacologic activity of Methadone.
Continuing in (Plaintiff expert, Ph.D.’s) report, third paragraph on page 3, “Blood specimen tests monitoring Methadone levels must be conducted.” The clinical signs and symptoms of opiate overdose are readily determined by direct observation and questioning of the patient. Performance of blood levels is rarely, if ever, required for this purpose. This is part of the titration and observation protocol utilized by the MMTP as the daily Methadone dose is increased, with its pharmacologic effects being monitored. Because of the enormous variation in tolerance, the clinical manifestations are more reliable than blood levels for this purpose. The titration procedures enforced and used in this patient as part of the treatment protocol provide for appropriate consideration of unusual tolerance in a patient being admitted to Methadone maintenance treatment.
In summary, (Plaintiff expert, Ph.D.’s) opinions are without scientific basis and fail to reach a level of reasonable medical probability.
(Plaintiff expert, M.D.), the other plaintiff expert, has been tendered as plaintiff expert in this case. He submits his opinions in a consultation of April 28th. On page 2, paragraph 2, he notes that the records “on page 5 of …..client with the name (Female) noted that she had no Methadone prior to February 24th.” I have been unable to locate that statement in the medical records. However, prior use of Methadone has been established in pre-existing medical records, particularly the records of primary care clinic, Bates stamped 000069, which notes that in October of 2002, the patient reports having used street Methadone three times in the previous 30 days, with a life time use of two years, having first used it at age 25. That this patient had experience with Methadone is supported by
the history given in 2002 and by the history of multiple relatives who have been on Methadone programs, stating that she was in fact referred to a Methadone program by her uncle who is on a Methadone program. That she was currently on opiates was established by the pre-admission urine reported as positive for opiates.
The statement by (Plaintiff expert, M.D.) that the usual starting dose for Methadone maintenance treatment is in the range of 20 milligrams is not the current State of the Art of induction into Methadone maintenance treatment except for circumstances where patients are well documented to have been opiate free for weeks to months prior to
admission and being re-admitted to Methadone maintenance, which is permissible in situations such as within six months of release from a penal institution and admitted to treatment while not currently physiologically addicted but at risk of resuming illicit opiate use.
(Plaintiff expert, M.D.) misstates the medical records in paragraph 3 on page 2, where he notes that the patient was on a dose of 70 milligrams of Methadone per day for a four-day period. Someone who is “extremely tolerant” to Methadone would have shown evidence opiate excess by the time they had received medication provided on the first day when the patient failed to respond within an hour to the oral dose of 30 milligrams, resulting in administration of an additional dose of 10 milligrams as permitted by the Federal and State regulations for induction into Methadone maintenance treatment.
Later in the third paragraph on page 2, (Plaintiff expert, M.D.) states “The average person would have had a similar fatal outcome if a similar dosage regimen was prescribed by (Physician).” (Plaintiff expert, M.D.) is correct in this statement concerning an average person but titration of her symptoms and time of onset of the symptoms monitored on a daily basis establishes that this patient was not “the average person” and was outside of the normal population by virtue of her tolerance to the increasing doses of Methadone.
(Plaintiff expert, M.D.) states “There is no question that this patient died of Methadone toxicity.” This is correct. There is no doubt, in my opinion, that the patient died of Methadone toxicity. However, there is no evidence that she died of Methadone toxicity as a consequence of the Methadone administered during the titration procedure for induction into Methadone maintenance as provided by the MMTP.
In the last paragraph on page 2 of (Plaintiff expert, M.D.)’s report, he states that the toxicology laboratory report without question shows a fatal blood level of Methadone of 1.5 milligrams per liter. He then proceeds to cite page 525 of Baselt’s “Disposition of Toxic Drugs and Chemicals,” where the average range of Methadone concentration in fatalities is stated to be 1 milligram per liter with a range of 0.4 to 1.8 mg/L. However, (Plaintiff expert, M.D.) chooses to omit mention of the statement on page 524 that states “With chronic administration of 100 to 200 mg daily oral doses of the drug to tolerant subjects, the plasma concentration again peaked at four hours with an average of 0.8, with a range of 0.57 to 1.6, and declined to 0.4 mg/L after 24 hours.”
Since the patient obviously was not unconscious at the time she departed from the treatment facility and was found dead at 3:07 p.m., she was beyond the four-hour peak as a result of the administration of an amount of Methadone well below the range discussed in Baselt, and had achieved a concentration well above that expected if she had been taking 50% to 250% higher doses per day of Methadone.
The sequence of events strongly supports that Methadone taken on the morning of her death was far in excess of the dose administered by the MMTP and obtained from sources other than the Methadone maintenance program. Again, as stated above in my discussion, the titration protocol where daily monitoring of withdrawal symptoms clearly demonstrates the patient to have not been pharmacologically naïve and to have had substantial tolerance for Methadone as a consequence of her ongoing opiate use. Tolerance to Methadone is not acquired exclusively from use of Methadone but there is cross-tolerance developed among the various opiates, and Methadone is the established standard for treatment and is useful to determine the existence of tolerance to the family of opiate drugs by the titration procedure as used by the MMTP.
Ultimately (Plaintiff expert, M.D.) opines that Methadone toxicity was the cause of death “with a degree of medical certainty” or as high as 95% probability, which is correct. However, nothing in (Plaintiff expert, M.D.)’s report, medical records or patient history establishes that the Methadone in the patient’s body at the time of death is the consequence of Methadone administered under careful control and observation by
the MMTP.
A number of publications are present in the medical literature of death occurring on days four to 10 of admission to Methadone maintenance programs where a daily increase in dose is ordered without daily observation of the health consequences of the previous day’s dose. Without exception, such experiences recorded in the medical literature occur when patients are admitted to Methadone maintenance treatment without appropriate medical supervision and surveillance.
(Plaintiff expert, M.D.) alleges that (Physician) is not familiar with the adverse reactions in drug-drug interactions that occurred in this patient. This is interesting because in the prior paragraph, he notes that death occurred without the significant presence of other drugs. Consequently, he does not believe that death was the result of a drug-drug interaction.
(Plaintiff expert, M.D.) opines that (Physician) administered “progressively increasing and fatal overdose to this patient.” There is no evidence that the Methadone administered by (Physician) accounted for the patient’s death. There is considerable evidence that the dose administered by (Physician) would be incapable of resulting in the high concentrations of Methadone present at the time of the patient’s death, as indicated by Baselt as cited by (Plaintiff expert, M.D.).
Eric G. Comstock, M.D.