Pain Medicine 2016; 17: 1793–1798
doi: 10.1093/pm/pnw074
The Opioid Drug Epidemic and Sickle Cell
Disease: Guilt by Association
In 2008, for the first time in Centers for Disease Control
and Prevention (CDC) history, death due to motor
vehicle accident was no longer the leading cause of
injury mortality non-medical death [1]. Drug overdose
was the number one cause of non-medical death in the
United States [1].
Since 2008, the number of deaths due to drug overdose has been increasing steadily [2–9]. The total number of deaths due to drug overdose was 36,450 in
2008 [10]. In 2013, the total amount of deaths due to
drug overdose was 43,982 [10]. Given the alarming
nature of these statistics, patients who requested an
opioid prescription became targets of suspicion and
possible accusation of being drug addicts and/or
drug seekers and possibly potential victims of overdose [8,9,11–15]. The advent of precision medicine
[16], however, seems to justify such behavior. Since
the pharmacodynamics and pharmacokinetics of an
opioid vary among patients considerably depending
on their individual specific genetic and epigenetic factors, it is conceivable that a certain opioid or a certain
dose of an opioid do not apply to all patients all the
time. Patients with sickle cell disease (SCD) whose
pain was treated with opioids chronically learned
which opioid and which dose of an opioid is best to
relieve or minimize their sickle pain. Nevertheless,
management of sickle cell pain with opioids must follow two tiers as is the case in the management of
other types of pain with opioids. The first tier is to
optimize analgesia by prescribing adequate dose to
minimize pain severity, and the second tier is to minimize risk by frequent monitoring and assessment of
opioid related adverse effects and outcomes related
to substance use disorders [17].
Although sickle cell pain is not a major feature within
the pain community and its many societies and publications, paradoxically, SCD patients are often
assumed to be associated with opioid abuse and
addiction [2–9,11–15,18–46]. The recently published
NIH guidelines for the treatment of the complications
of SCD [47,48] reviewed the literature that pertains to
all these issues. The expert panel of the guidelines
determined it was important to include current practices that have not yet been validated by evidence, but
are based on the consensus and panel expertise.
Recommendations were included to improve the care
of patients in the emergency department (ED) and hospital and to guide providers in managing persons who
take both long- and short-acting opioids to manage
pain at home. Most important among these was to
determine the characteristics, associated symptoms,
location, and intensity of pain based on patient selfreport and observation.
Due to this frequent perception of patients with SCD
and opioid pain reliever (OPR) use, we researched the
CDC database [10] to determine how many patients
with SCD died from OPR overdose [10].
The CDC Multiple Cause of Death database covers the
number of deaths from 1999 until 2013 [10]. We conducted searches using the same ICD-10 codes that the
CDC used to determine the number of deaths due to
OPRs in general and to SCD in particular. This is the
same database used by journalists and scientists to verify how death due to OPR has become a national epidemic. Moreover, it is well established now that the
mortality of patients with SCD has decreased significantly over the last 20 years, although the use of
opioids by patients with SCD remained the same [49].
In 2008, 14,795 people (not including patients with
SCD) died due to OPR overdose [2,10]. That same
year, only five patients with SCD died due to OPR overdose as shown in Table 1 [10]. In 2013, 16,225 people
died due to OPR overdose while only 10 patients with
SCD died due to OPR overdose (Table 1). The same
trend was seen every single year from 1999 until 2013
(Table 1). The highest number of deaths due to SCD
and OPR overdose was 10, which occurred in 2010,
2011, and 2013 (Table 1). From 1999 until 2013,
174,959 people died due to OPR overdose while in the
same time period only 95 patients with SCD died due to
OPR overdose (Table 1).
Moreover, with the exception of heart disease, the number
of deaths due to OPR in patients with SCD was less than
other non-cancer pain conditions including fibromyalgia,
low back pain, and migraine (Table 2). Furthermore, the
number of patients with SCD who died due to OPR was
C 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: [email protected]
V
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Ruta and Ballas
Table 1 Comparing number of deaths due to
opioid pain relievers of non–sickle cell disease
patients with the number of deaths due to opioid
pain relievers of sickle cell disease patients from
1999 to 2013 in the United States
Year
Non-SCD Patients
Who Died Due to OPR
SCD Patients Who
Died Due to OPR
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
2011
2012
2013
Totals
4,022
4,393
5,521
7,450
8,513
9,856
10,922
13,717
14,401
14,795
15,594
16,641
16,907
16,002
16,225
174,959
8
7
7
6
4
1
6
6
7
5
3
10
10
5
10
95
OPR ¼ Opioid Pain Reliever; SCD ¼ Sickle Cell Disease.
Reference: Multiple Cause of Death Data, 1999-2013. CDC
WONDER Online Database. 2015. Available at http://wonder.
cdc.gov/mcd.html.
significantly less than the total number of all patients with
other diagnoses who died due to OPR (Table 3). Death
certificates and autopsies done on patients with SCD
always indicated the presence of SCD [50].
Zempsky noted that there exists “a negative attitude
towards patients with SCD and a profound fear of catering to opioid addiction” and that clinicians assume that
opioid addiction is more likely in patients with SCD than
other chronic pain syndromes [23]. Tanabe et al. found
that patients who are suffering from a vaso-occlusive
crisis “experienced significant delays to administration of
an initial analgesic” [51]. According to Chestnut, parents
or guardians of children with SCD believed that
Caucasians received better treatment than African
Americans [52].
Dorsey et al. found that patients with SCD reported that
nurses were not that caring with them compared to
how the same nurses treated others with different medical conditions [53]. Labbé et al. found that physicians
who treated patients with SCD were inclined to have
the belief that patients with SCD were addicts and
therefore results in patient pain being undertreated [19].
Many other studies have found that racial and ethnic
minorities tend to be undertreated for pain compared to
non-Hispanic whites [32,54,55].
1794
Sixty-three percent of nurses believed that patients with
SCD were OPR abusers and that 30% were concerned
about giving patients with SCD high doses of OPR [20].
Shapiro et al. found that 53% of emergency room (ER)
physicians and 23% of the hematologists surveyed
thought that more than 20% of patients with SCD were
drug addicts [21]. Waldrop and Mandry reported that all
the health professionals they surveyed were wrong in
their estimates about the prevalence of drug addiction
in patients with SCD [22].
Although the medical literature indicates that death due
to OPR is on the rise, as is addiction [1–3,6–
9,12,27,28,33,34,40], this does not automatically mean
that patients with SCD who take high amounts of
OPRs are drug addicts. Sickle cell pain is unique and
different than other types of pain. Patients with low
back pain or with fibromyalgia develop these as adults
and do not usually utilize the ED and hospital for pain
management; their treatment is mostly on an outpatient
basis. Sickle cell pain, by comparison, is due to an
inherited disorder and manifests itself at the age of 6
months and continues through the life span of the
affected patient. Accordingly, it is by common sense
that patients with SCD do consume larger amounts of
opioids on a chronic basis and require frequent admissions to the ED and/or the hospital. A prospective longitudinal and observation cohort study of adult patients
with sickle cell anemia admitted to one institution
between January 1998 and December 2002 showed
that, on average, an adult patient with SCD was admitted to the hospital four times per year and the average
length of hospital stay was 7.6 days [56]. Moreover,
about 16% of all admissions were within 1 week after
discharge.
It must be noted that we do not advocate the use of
high doses of opioids to treat pain in patients with
SCD. We advocate the adequate treatment of sickle
cell pain that offers pain relief and better quality of life.
This can be achieved by listening to the patients and
respecting their self-report about the severity of pain
as recommended in the National Institutes of Health
(NIH) guidelines. These NIH guidelines also specifically
state that the provider should “base analgesic selection
on pain assessment, associated symptoms, outpatient
analgesic use, patient knowledge of effective agents
and doses, and past experience with side effects” [48].
This almost always includes the use of an opioid. In
addition, on January 11, 2016 the American Society of
Hematology (ASH) sent a letter to the CDC commenting on the Proposed 2016 Guidelines for Prescribing
Opioids for Chronic Proposed 2016 Guidelines for
Prescribing Opioids for Chronic Pain (Docket No.
CDC-2015-0112) [57]. In this letter, ASH specifically
requested that the scope of these Guidelines be clarified to exclude patients with Sickle Cell Disease and
patients undergoing active treatment for cancer because
pain in these patients is complex and better addressed
by the recently published NIH guidelines mentioned
above [48,57].
Opioid Epidemic and Sickle Cell Disease
Table 2 Total number of deaths due to opioid pain relievers in different non-cancer disorders from
1999 – 2013 in the United States
Cause of Death
Total Number of Deaths Due to All Causes
Death Due to OPR
Percentage
Heart Disease
Fibromyalgia
Low Back Pain
Migraine
Sickle Cell Disease
20,595,492
3,282
3,758
2,286
12,261
21,656
144
80
103
95
0.11
4.4
2.1
4.5
0.77
OPR ¼ Opioid Pain Relievers.
Reference: Multiple Cause of Death Data, 1999-2013. CDC WONDER Online Database. 2015. Available at http://wonder.cdc.
gov/mcd.html.
Table 3 Statistical data of deaths due to opioid
pain relievers of total number non–sickle cell
disease patients and patients with sickle cell
disease from 1999 – 2013 in the United States
Total Number of
Patients with
Non-Sickle Cell
Sickle Cell Disease
Disease Patients
Who Died Due to OPR Who Died Due to OPR
Mean*
(15) 11,664 6 4701
P Value P < .001
(15) 6.3 6 2.58
*(number of years 1999-2013 from the CDC WONDER Online
Database) mean 6 Standard Deviation; OPR ¼ Opioid Pain
Relievers.
It is well known that the common causes of death for
patients with SCD are sepsis, acute chest syndrome,
sudden death, and organ failure. References about mortality in patients with SCD list infection, stroke, acute
chest syndrome, sudden death, and organ failure.
Opioids are not mentioned in these studies as a cause
of death [58–60].
Treatment of patients with sickle cell anemia with
hydroxyurea decreased the frequency of VOCs and of
acute chest syndrome, improved their quality of life, and
decreased morbidity and mortality. Moreover, patients
who responded to hydroxyurea consumed less opioids
during crises and their length of hospital stay decreased
by an average of 2 days [61]. This study also determined the consumption of opioids at home, during
acute care, and in the hospital [61]. The study found
that the opioids most commonly used at home were
Oxycodone and Codeine followed by Meperidine and
others. The mean oral daily dose for at home use was
15.5 mg (31 mg Morphine mEq) for Oxycodone, 79.8 mg
(12 mg Morphine mEq) for Codeine, and 186.7 mg
(18.7 mg Morpphine mEq) for Meperidine. The opioid
most commonly used during hospitalization was
Meperidine in 75.3% of the patients (in the 1980s and
1990s Meperidine was the most commonly used opioid
to treat SCD pain) followed by Morphine in 19% of the
patients and Hydromorphone in 15.6% of the patients.
The numbers do not add up to 100% since patients
often use more than one opioid to achieve adequate
pain relief. The mean parenteral daily dose during hospitalization was 523.4 mg (69.8 mg Morphine mEq) for
Meperidine, 53.3 mg for Morphine, and 30.2 mg
(201.3 mg Morphine mEq) for Hydromorphone.
Although not all physicians view patients with SCD negatively, the literature is full of evidence that shows that
the majority do due to the high dosage use of OPR [19–
23]. Admittedly, there are some patients with SCD who
abuse OPRs and the system. Actually these patients are
the exception and not the rule and are often used as
anecdotal evidence that all patients with SCD are drug
abusers [18]. However, to label an entire group based
on the actions of the few does not constitute proper
medical care.
It is well known that the solution to any type of relationship issue is communication. Both patient and provider have to realize that instead of having an
adversarial relationship they should aim at creating a
collaborative relationship [25,62–65]. Both patient and
provider are a team with the sole purpose of making
sure that the patient’s pain is under control and that
the patient remains as healthy as possible given the
circumstances of the disease [65,66]. This was
achieved by the creation of individualized pain plans
that resulted to less frequent admissions, less waiting
time in the ER, and shorter length of hospital stays
[66,67].
Another key tool is the use of empathy [62,64,68]. This
does not mean that the provider ignores potential warning signs and risks that something is amiss that requires
further counseling. The use of prescription drug monitoring programs (PDMP) can easily assist the physician in
discovering their patients’ prescription history [43,65]
without having to immediately assume that drug abuse
is taking place.
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Ruta and Ballas
Bediako and Moffitt suggest that providers should be
educated about SCD in order to help diminish false
racial perceptions [69]. Another potential solution is for
the medical community to accept the current reality that
one of the major methods to treat pain in patients with
SCD is the use of OPR. Often there is a perception that
vaso-occlusive pain can be treated without the use of
OPR because OPRs are “bad” [44,70]. The pain of a
patient with SCD is not the same type of pain as in
other pain conditions.
In conclusion, in order to help patients with SCD, they
should be respected, listened to, believed, and treated
with the best means available. Currently, the use of
OPRs is one of the most commonly used methods.
Until we find a so-called “holy grail” for the non-opioid
management of pain [71], providers and patients with
SCD have to foster a sense of teamwork. Suspicion and
guilt, although rooted in concern and respect for the
law, do not constitute a solution to a serious problem.
An adversarial relationship never leads to or creates a
permanent solution. The current national opioid phobia
may, unwittingly, deny opioids to patients who really
need them, especially those patients who experience
recurrent episodes of acute pain such as patients with
SCD.
NADIA S. RUTA, JD and SAMIR K. BALLAS, MD, FACP
Department of Medicine, Thomas Jefferson University,
Philadelphia, Pennsylvania, USA
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