Pain Medicine 2010; 11: 14191425
Wiley Periodicals, Inc.
FORENSIC PAIN MEDICINE SECTION
Case Report
Allegations of Medical Malpractice in Chronic
Opioid Analgesic Therapy Possibly Related to
Collaborative/Split Treatment and the P-450
Enzyme System: Forensic Case Report
David A. Fishbain, MD, FAPA,* John E. Lewis, discuss issues potentially related to these allega-
PhD,* and Jinrun Gao, MS, MBA
Departments of *Psychiatry,
Neurological Surgery and Anesthesiology, Miller
School of Medicine, University of Miami;
The Rosomoff Comprehensive Pain & Rehabilitation
Center, Douglas Gardens;
Department of Psychiatry, Miami Veterans
Administration Hospital, Miami;
State Farm Insurance, Bloomington Illinois, USA
Reprint requests to: David A. Fishbain, MD, FAPA,
Department of Psychiatry, University of Miami, 1695
NW 9th Avenue, Suite 3302L (D-79), Miami, FL 33136,
USA. Tel: 305-355-9021; Fax: 305-668-0578; E-mail:
d.fishbain@miami.edu.
Summary
A medicolegal forensic case report of allegations of
medical malpractice during chronic opioid analgesic
therapy is presented. Here, issues relating to split
treatment and the P450 enzyme system are
discussed.
Abstract
Objectives. The objectives of this forensic
medicolegal case report were the following: 1)
present details of a patient on chronic opioid
analgesic therapy (COAT) where a disastrous
outcome resulted in allegations of malpractice;
2) detail the plaintiffs and defendants medical
experts opinions on this allegation; and 3)
pme_928 1419..1425
tions, i.e., split treatment and the P450 enzyme
system.
Methods Case Report Results. Medicolegal issues
surrounding these malpractice allegations are
discussed.
Conclusions. Split treatment can increase the diffi-
culties in performing COAT. Clinicians should rou-
tinely consider the effects of all utilized drugs on the
ability of the P450 enzyme system to metabolize/
clear opioids.
Key Words. Chronic Pain; Medical Malpractice Alle-
gations; Intractable Pain; Opioids; Chronic Opioid
Analgesic Therapy; Standards of Medical Care;
Breaches of Standards; Aberrant Drug Related
Behaviors; Split Treatment; P-450 Enzyme System;
CYP 2D6
Introduction
Chronic opioid analgesic therapy (COAT) for chronic benign
nonmalignant pain [1,2] has generated controversy [3]. In
addition, treatment issues surrounding COAT have gener-
ated the potential for malpractice litigation [4,5]. Some of
these issues have been explored in forensic case reports of
alleged malpractice relating to COAT. These are the follow-
ing: death from opioid rotation to methadone [6]; suicide
related to opioid tapering for alleged addiction [7]; motor
vehicle accident allegedly related to opioid placement [8];
patient overdose death where the physician was noncom-
pliant with Model Guidelines [9]; alleged medical abandon-
ment during COAT [10]; and allegations of iatrogenic opioid
addiction allegedly related to COAT [11]. All of these cases
have been presented from the standpoints of the plaintiffs
and defendants medical experts. This is crucial as it is
important for the pain community to understand how
experts are viewing the current standard for COAT.
The alleged COAT malpractice case described below
relates to issues not previously identified by the medical
1419
Fish Bain et al.
experts and not presented or discussed in this literature:
split treatment and the effect of drugs on the ability of the
P450 enzyme system to metabolize opioids.
Case Report
Mr X was a 50-year-old black male who presented to a
pain physician after two failed laminectomies at L4-L5 and
L5-S1 2 years previously. He had originally injured his back
in a worker compensation accident, falling from a two-
story roof 4 years pre-presentation. The orthopedic
surgeon had deemed him not to be a candidate for further
surgery and had referred him for an epidural trial. At pre-
sentation, he was on oxycodone 5 mg/acetaminophen
325 mg eight tablets per day, but complained of 10/10
back pain. Mr X denied any previous drug/alcohol history,
but did admit to being under the care of a psychiatrist for
depression and posttraumatic stress disorder related to
the fall from the roof. He was on diazepam 5 mg t.i.d.,
trazodone 200 mg h.s., and fluoxetine 20 mg q.a.m. from
his psychiatrist. Physical examination was within normal
limits except for impaired ranges of motion of the lumbar
spine for flexion/extension/lateral flexion/ rotation. Trigger
points were present bilaterally at the paraspinal muscula-
ture. Medical records (since the accident) were made
available by the carrier and were reviewed. There
appeared to be no other pertinent information in these
records. Diagnoses were failed back syndrome and myo-
fascial pain syndrome.
Mr X was given three epidural injections and a series of
trigger point injections with little effect on his pain. He was
then deemed not to be a candidate for further interven-
tional treatments. Referral to a multidisciplinary pain treat-
ment program was refused by the carrier. As he now was
a candidate for COAT at this point, Mr X was rotated to
controlled-release oxycodone, which was slowly titrated
up to 200 mg per day (five 40 mg pills per day) with a
decrease in pain to 57/10.
Mr X was seen over a period of 1.5 years every 2 months
during which time he was maintained on the same dose of
controlled-release oxycodone. During this period, random
urine toxicologies were negative for illicit drugs, but there
were five incidents of aberrant drug-related behaviors
(ADRBs) [1,2,1216] (early refills, utilizing oxycodone not
as prescribed, obtaining opioids from additional physi-
cians). As a result, Mr X was referred for consultation with
an addictionologist familiar with chronic pain patients
(CPPs). Diagnosis here was pseudo-addiction [1,7,17]
and as a result, Mr X was maintained on COAT.
Three days after his last visit to the pain physician, at
which time no medications changes were made, Mr X was
found dead in the bathroom. The CR oxycodone had
been filled one day previously and there were eight pills
missing from the bottle.
The medical examiners autopsy results were as follows:
no major anatomical findings; status post-lumbar laminec-
tomy and diskectomy; oxycodone plasma levels (femoral)
1420
2,000 ng/mL; diazepam plus nordiazepam plasma level of
450 ng/mL (toxic level considered to be 3,000 ng/mL or
above); trazodone level 200 ng/mL (toxic levels reported
above 5001,100 ng/mL); and fluoxetine plus norfluoxet-
ine plasma levels 450 ng/mL (reference range 150
463 ng/mL, toxic levels reported above 1,000 ng/mL). All
plasma levels had been determined by gas
chromatography/mass spectometry. Medical examiners
opinion was as follows: high toxic levels of oxycodone;
therapeutic levels of diazepam, nordiazepam, trazodone,
fluoxetine, and norfluoxetine; unclear if cause of death
intentional or accidental; and cause of death oxycodone
toxicity.
One year after Mr Xs death, medical malpractice suits
were launched against the pain medicine physician and
the psychiatrist. The medical malpractice allegations
against the pain physician, according to the plaintiffs
medical expert, were the following. The defendant fell
below the standard (the provision of care in accordance
with the conduct of a prudent and diligent doctor in the
same circumstances) in the following areas: 1) the defen-
dant failed to monitor Mr X for the development of toxic/
lethal levels of oxycodone; 2) the defendant failed to warn
Mr X about potential toxic reactions between diazepam/
nordiazepam and oxycodone; and 3) the defendant failed
to monitor medications received from other physicians.
The plaintiffs malpractice allegations against the psychia-
trist are unknown, as these two malpractice cases were
defended separately.
The plaintiffs and defendants medical experts in their
review of the case had access to Mr Xs pre- and post-
worker compensation injury records and to the medical
records of both defendants. The salient aspects of these
records relevant to this case are the following. Mr X pre-
pain treatment had a long history of illicit drug abuse/
dependence, which he had withheld from both
defendants. Mr X was being treated by the psychiatric
defendant for depression and PTSD and was at times
suicidal. At the time of his last visit with the psychiatrist (2
weeks before his death), he had been on 40 mg of fluox-
etine per day, but continued to be depressed. As a result,
the fluoxetine was increased to 60 mg per day. No other
changes in medications were made that day by the psy-
chiatrist. There was no documentation in the psychiatrists
chart as to whether Mr X was taking oxycodone, although
the chart indicated that Mr X was going to a pain physician
and was on opioids for his pain. All medications pre-
scribed by the psychiatrist were documented in the psy-
chiatric chart. In the pain medicine physicians chart there
were no notes (after the evaluation note) relating to the
current psychotropic regimen being administered by the
psychiatrist.
The defendants medical expert responses to the allega-
tions of the plaintiffs medical expert were as follows. Mr X
had been on the same dose of oxycodone for 1.5 years
and was very likely tolerant to that dose. If the cause of
death was oxycodone toxicity, then this was the result of
one or a combination of the following: a) Mr X took more

oxycodone than prescribed (as evidenced from pills
missing) in order to get high (as evidenced by the previous
history of illicit drug use and ADRBs) or as a suicide
attempt (as evidenced by the previous history of being
suicidal); or b) Mr X had a toxic reaction to oxycodone as
a result of the recent increase in fluoxetine, or c) Mr X had
a toxic reaction possibly as a result of b) above and/or
being a CYP 2D6 slow metabolizer [18]. Most likely cause
of death if from oxycodone toxicity was secondary to
taking more oxycodone than prescribed in association
with the increase in the fluoxetine dose. The defendants
medical expert could not defend the pain medicine phy-
sician against the allegation of not monitoring the psy-
chotropic medications received from other physicians.
The defendants medical expert also gave the opinion that
because Mr X was tolerant to the oxycodone that the
measured post-mortem plasma oxycodone level may not
have been toxic to Mr X. The case was subsequently
settled for a nominal sum.
Discussion
A number of aspects of the opinions held by plaintiffs and
defendants medical experts in reference to Mr Xs case
require special comment as they are new and unique to
the COAT litigation literature. These are outlined below.
The P-450 Enzyme System and Oxycodone and
Fluoxetine Metabolism
The defendants expert indicated that he believed that if
Mr X died from oxycodone toxicity that this could have
been the result of the increase in fluoxetine by the psy-
chiatrist shortly before the death. What is this belief based
on?
Drug metabolism occurs through the cytochrome P-450
liver enzyme system (Phase I) and through conjugation
(Phase II). The phase I enzymes most responsible for drug
metabolism are the cytochromes CYP 3A4/3A5, CYP
2D6, CYP 2C9, and CYP2D9 [19]. By far the most preva-
lent and dangerous drug-drug interactions occur through
cytochrome metabolism [19]. This is because many drugs
inhibit the activity of some of these cytochromes thereby
decreasing the metabolism of other drugs. This can result
in an increase in the serum level of these other drugs
thereby causing drug toxicity [20].
In reference to Mr Xs case, 2D6 is a major pathway for
oxycodone where oxycodone is metabolized to oxymor-
phone, an active opioid analgesic. However, oxycodone is
not a prodrug and is a potent analgesic in its own right
[21]. Thus, interference with 2D6 metabolism will increase
levels of oxycodone, resulting in potential toxicity. Fluox-
etine and its metabolite norfluoxetine are potent inhibitors
of 2D6 [22,23]. In addition, they mildly to moderately
inhibit CYT 1A2, 2B6, 2C9, 2C19, and 3A4 [22]. There-
fore, fluoxetine has been called a P-450 pain-inhibitor.
Thus, in Mr Xs case, there may have been little 2D6
activity left for the metabolism of oxycodone. In addition,
diazepam is metabolized by CYP 1A2, 2C19, and 3A4,
Allegations of Medical Malpractice
which are also all mildly to moderately inhibited by
fluoxetine/norfluoxetine [22]. The inhibition of diazepam
metabolism could then have led to a buildup of diazepam
and an interaction with oxycodone. In addition, Mr X was
on trazodone, which is metabolized by 3A4. As noted
above, fluoxetine is an inhibitor of 3A4. Although the post-
mortem trazodone plasma levels were not elevated, the
presence of trazodone would have also added to the
burden of diazepam metabolism, thus increasing the pos-
sibility of a synergistic interaction between diazepam and
oxycodone.
Was Mr X a Poor Metabolizer of Oxycodone?
The P-450 enzyme system is subject to genetic polymor-
phism. As such, patients have been classified as poor,
intermediate, extensive, and ultra rapid metabolizers of
various drugs proportional to the number of allele copies
of the gene carried [18]. For example, for clearance of
nortriptyline, poor metabolizers have zero copies of the
gene for the P-450 enzyme CYP2D6, while intermediate
metabolizers have one, extensive metabolizers two
copies, and ultrarapid metabolizers have more than two
copies [18]. Slow metabolizers of CYP2D6 make up to 2%
of African Americans [18]. There has been concern in the
literature that as 2D6 is a major pathway for oxycodone
clearance that toxicity could occur with oxycodone in
patients with genetically poor 2D6 metabolism or in the
constant presence of a strong 2D6 inhibitor, such as flu-
oxetine [21,24]. There is some evidence for this belief. In a
post-mortem analysis of 15 deaths where suspected oxy-
codone toxicity was the cause of death, there were two
and possibly six deaths that occurred in patients geno-
typed as poor 2D6 metabolizers. Four of these cases
helped better interpret the oxycodone toxicity [25]. As
such, according to these limited studies, it is possible that
Mr X could have been a poor 2D6 metabolizer. This in
combination with the increase in fluoxetine dose escala-
tion causing increased 2D6 inhibition could have contrib-
uted to the oxycodone toxicity.
Toxic vs Lethal Plasma Levels of Oxycodone
Mr Xs post-mortem oxycodone plasma level was
2,000 ng/mL, which the medical examiner identified as a
high toxic level and as a cause of death. The forensic
literature indicates that levels of 2005,000 ng/mL are
considered toxic, while the lethal range has been reported
to be between 4,300 and 14,000 [26]. However, the lethal
range has been reported to be as low as 400700 ng/mL
when oxycodone is combined with another central
nervous system depressant [26], as was in Mr Xs case.
The defendants medical expert opinioned that Mr Xs
oxycodone level may not have been toxic or lethal, as Mr
X was tolerant to the oxycodone dose prescribed. This
was based on recent reports in the pain literature where
Tennant [27] has claimed that the oxycodone therapeutic
range in nontolerant patients is from 100 to 400 ng/mL,
while levels as high as 3,077 ng/mL have been registered
in opioid tolerant CPPs. These tolerant CPPs appear not
to demonstrate any signs of toxicity at these very high
1421
Fish Bain et al.
plasma levels [27]. These findings have recently been mir-
rored in the forensic literature. Here, Jung and Reidenberg
[28] concluded that that some CPPs on large doses of
opioids have high plasma opioid levels that overlap levels
measured in post-mortem studies [28]. Some opioid levels
considered fatal in forensic cases have come from non-
tolerant patients who had additional depressant drugs in
the system and may have died from the effects of the
combination [28]. Interpreting these levels as fatal in tol-
erant patients can be incorrect [28].
Is There Relevant Case Law to the Case of Mr X?
The authors were able to find a number of case law cases
that apply to some of the issues raised by this case. These
were the following. Negligent use of medications (exces-
sive dosing, inadequate dosing, and inappropriate medi-
cation; failure to obtain informed consent; and failure to
monitor blood levels) is a common reason for launching a
malpractice suit [29]. It has been advocated that in cases
where drug-drug interactions are known to result in inhi-
bition of a specific agents metabolism, prescribing an
agent at otherwise normal doses might be viewed as
excessive dosing by the courts [29]. This was the possible
situation with Mr X in reference to fluoxetine. A case law
case applies here. A chronic asthmatic on theophylline
was appropriately dosed with ciprofloxacin, which
resulted in seizures secondary to theophylline toxicity. The
patient was left with permanent brain damage. This
resulted in a $23 million award against a physician and a
pharmaceutical company. Ciprofloxacin potently inhibits
CYP 450 1A2, which theophylline is dependent on for
clearance [30].
As pointed out in the discussion, there are difficulties with
applying what are currently thought to be toxic and lethal
opioid (oxycodone) plasma levels to deceased patients
who had chronic pain and were possibly tolerant to
opioids. There are a couple of case law cases that apply
here. In 1999, a physician was charged with three counts
of murder allegedly as a result of lethal oxycodone doses.
In one of these cases, a woman died in a motor vehicle
accident, who at autopsy had an oxycodone plasma level
of 21,900 ng/mL. A forensic pathologist testified that by
extrapolating from published sources about oxycodone
plasma concentrations, this patient would have to have
taken 220, 80-mg CR-oxycodone tablets to achieve the
level reported. However, only two pill fragments were
found in her stomach. In the second death, a woman had
an oxycodone plasma level of 2,290 ng/mL, as well as six
other substances. The third death was of a man judged to
have died from asphyxia secondary to oxycodone intoxi-
cation with a blood level of 1,010 ng/mL. The first case
was discharged by the judge who commented that he
could only conclude that the test findings resulted from an
error in collection or testing or that the patient had com-
mitted suicide. Murder charges were also dismissed for
the other two patients [31]. In the second law case, fol-
lowing back surgery, a patient was prescribed
CR-oxycodone for pain relief. Three days later, he was
found dead by his wife. Autopsy revealed alleged toxic
1422
levels of oxycodone and the medical examiner concluded
that death was secondary to accidental acute oxycodone
toxicity. The plaintiffs medical expert testified that the
patient died from an accumulation of oxycodone. He had
reached this conclusion by utilizing a computer program
to determine the biological parameters a hypothetical
person would need to have to reach the toxic levels of
oxycodone found in the patients system, assuming he
took the medication as prescribed. The trial court found
that there was no scientific basis for the plaintiffs experts
conclusions that death was the result of accumulation vs
an overdose. As the experts testimony was unreliable, the
case was dismissed [32].
As presented in Mr Xs case report, neither the treating
pain physician, nor the treating psychiatrist had docu-
mented the medications that the other was prescribing.
The pain medicine physicians medical expert noted that
he could not defend the defendant against the lack of
documentation and its potential impact on the prescribing
of the oxycodone. Clarity of role, of function, and of clinical
decision-making is key to assessing whether a physician
has met the standard of care [33]. Clarity is assessed
through an examination of the individuals role and how it
was executed, whether there is one player or several. In
situations where there is more than one physician, the
courts focus on certain individualized questions: Did
everyone have complete information? Did everyone know
what he/she was supposed to do and how to do it? Did
each physician know what the other was doing [33]? This
is illustrated in the following case law case. Here, the
patients family physician, consulting specialist, and E.R.
internist were all held liable when all three failed to convey
to each other various observations made about the
patients condition. This resulted in a fatal aneurysm [34].
Thus, documentation of all medications the patient is on at
each visit is essential in collaborative/split treatment.
What Actions Can or Should the Pain Physician Take
to Avoid Drug-Drug Interactions (DDIs)?
The vast majority of CPPs on COAT are also on other
drugs for associated comorbidities, such as antidepres-
sants and anticonvulsants, or on these drugs for their
pain. Thus in terms of CPP treatment polypharmacy [35] is
the rule rather than the exception and, as such, the CPP
is subject to significant DDI risk. A number of approaches
to mitigating the risk for DDIs and associated malpractice
risk have been suggested in the psychiatric literature, but
have not been discussed or addressed in the pain litera-
ture. These are the following: 1) at each visit, review with
the patient each medication being taken and document
the medication and dose [36]. This should also include
over-the-counter medications, supplements, and herbal
remedies; 2) advise patient that he/she must tell you if any
physician has made any additions or any changes to
his/her medication regimen and document that the patient
has been advised to do this [36]; 3) educate the patient
about potential side effects and potentially lethal side
effects and document that patient has been advised of
this [36]; 4) educate the patient that street drugs, such as

cannabinoids, cocaine, etc., and alcohol can accentuate
DDIs by their effect on the P450 enzyme system and
document that this information has been given [36]; 5)
initiate the potential victim drug (plasma level can be
affected by the inhibitor) at low dose and increase the
dose of that drug gradually after assessing the patients
response [37]; 6) keep the dose of the inhibitor low or if
absolutely necessary to increase dose, do so very gradu-
ally [37]; 7) consider utilizing drugs that are metabolized by
multiple P-450 enzymes rather one CYP system [37]; 8)
be aware of which drugs are strong inhibitors of CYP
system, e.g., fluoxetine, as in the case of Mr X [37]; 9)
therapeutic drug monitoring is indicated where there is a
meaningful relationship between drug plasma concentra-
tion and its concentration at site of action. Failure to
appropriately monitor drug plasma levels where therapeu-
tic and toxic levels have been established could represent
negligent care if an adverse drug reaction resulted from
drug toxicity [29]. Unfortunately, as pointed out in the
discussion, there is controversy about the value of oxyc-
odone plasma levels. As such, the measurement of oxy-
codone plasma levels and some other opioids (fentanyl,
hydrocodone, hydromorphone, methadone, and mor-
phine), although available, is not currently being routinely
done in COAT. Thus, opioid therapeutic drug monitoring is
not now considered a standard in COAT care. The
current literature and Mr Xs case indicate that there could
be two potential values to opioid plasma levels: a) theo-
retically, a very high plasma level of an opioid at a low
dose could alert the clinician to the possibility that the
patient could be a poor metabolizer and CYP2D6 geno-
typing could then be requested for confirmation if available
and/or deemed to be cost effective [18]; and b) if a patient
registers a high potentially toxic opioid level and does not
display any side effects, then that patient is tolerant to the
current opioid dose [27]. Documentation of such informa-
tion could have prevented some of the confusion in Mr Xs
case as to what his post-mortem oxycodone level meant;
10) finally, at the present time there is software available for
personal digital assistants that incorporates pharmacoge-
netics and drug-drug- interactions (Gene Medical Rx). In
addition, it appears that the currently available drug-drug
interaction programs have high sensitivity and specificity
for detecting DDIs [38]. The ePocrates Rx program has
been rated as being very reliable and it is updated regularly
and is available on the Internet [38]. These programs could
potentially help in mitigating the risk for DDIs.
As noted above, the physician now has the ability to order
genotyping for his patients. At issue then is whether such
testing has analytic validity, clinical validity, and clinical
utility. In 2005, the FDA approved the Amplichip CYP450
test to detect CYP2D6 and CYP2C19 polymorphisms
based on evidence that the tests had high sensitivity and
specificity [39]. As such, this testing has analytic validity.
Clinical validity for genetic testing can be examined in
reference to two questions: does it improve drug
response; and does it decrease the frequency of side
effects. In 2007, the genomic application in practice and
prevention (EGA PP) working group attempted to answer
the first question by examining the evidence for improve-
Allegations of Medical Malpractice
ment in depression with selection of treatment with selec-
tive serotonin inhibitors (SSRI) by genetic testing. They
determined that there was no evidence available that
genetic testing improved depression outcomes. They
noted that these data could be affected by the fact that
some SSRIs are metabolized by more than one CYP450
enzymes. There are however examples of where genetic
testing can improve outcomes with other drugs. For
example, catechol-O-methyltransferase (COMT) polymor-
phism is important to propranolol metabolism. It was
recently demonstrated that propranolol significantly
decreased a composite pain index in musculoskeletal
pain. When patients were stratified by COMT high activity
haplotype (fast metabolizers), a beneficial effect of propra-
nolol on pain perception was noted in patients not carrying
this haplotype [40]. Overall however, the evidence for
improved drug response is mixed and genetic testing for
this application presently has little clinical utility [41]. In
reference to whether polymorphism testing can decrease
the frequency of side effects, the same situation persists.
Here there has only been one study [42]. In this study,
80% of patients reporting adverse drug reactions on
opioids had impaired CYP2D6 metabolism (were slow
metabolizers) [42]. Again however, overall presently 2D6 or
2C19 testing to decrease side effects has little evidence
for clinical utility. This is the reason why genetic polymor-
phism testing cannot presently be considered a stan-
dard. Thus, the plaintiffs expert did not raise failure to
do polymorphism testing as a breach. However, the
defendants expert can and did raise genetics as a poten-
tial issue as to the cause of death. The other reason why
polymorphism testing is not generally utilized is cost.
Although available commercially, these tests are not
covered by insurance and can range from $500 to $1,000.
A final issue that relates to mitigating DDIs, not noted by
either expert is that of sleep apnea-opioid association.
This association was first suspected in 2001 [43] when 6
of 10 patients in a methadone maintenance program for
heroin addiction were discovered to have central sleep
apnea. It was then demonstrated that patients with sleep
apnea were more likely to have central sleep apnea than
their counterparts not taking opioid medications [44]. This
was followed by a study [45] which demonstrated that
75% of pain patients on around-the-clock opioid therapy
for at least 6 months had some form of sleep apnea. Of
these, there was a direct relationship between the apnea-
hypopnea index and daily methadone dose, but not other
around-the-clock opioids and a direct relationship
between the central apnea index and daily methadone
dosage and benzodiazepines. It is to be noted, however,
that it is not clear at the present time if opioids actually
cause central sleep apnea in individuals not having this
problem pre-opioid use as prospective studies are lacking
[43]. However, there is one report of three cases where
central sleep apnea was actually induced by acute inges-
tion of opioids [46]. How does this association relate to the
case of Mr X? Mr X was on an opioid and a benzodiaz-
epine. The above discussion then indicates that induction
of central sleep apnea by opioids/benzodiazepines could
possibly have been a factor in the death. However, the
1423
Fish Bain et al.
plaintiffs expert did not identify failure to obtain sleep
studies pre-opioid and post-opioid placement as a
breach. This is likely to be because, as pointed out above,
the evidence for this association is in process of develop-
ment. As such, pre- and post-opioid sleep studies are
currently not yet a standard for COAT. However, it is
possible that these types of studies will be utilized to
develop a standard.
Conclusions
Split treatment can increase the difficulties in performing
COAT. In performing COAT, clinicians should consider the
effects of the drugs utilized on the ability of the P-450
enzyme system to metabolize/clear opioids and the
effects of opioids and other drugs on sleep architecture.
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