Transcript No Slide Title

Chronic Pain, Functional
Status, and Quality of
Life in Sickle Cell
Disease
Wally R. Smith, MD
Professor and Chairman, Division of Quality Health Care
Principal Investigator, VCU Basic and Translational
Research Program in Sickle Cell Disease
Principal Investigator, VCU Sickle Cell Disease
Outcomes Research Center, SCD Clinical Research
Network
Learning Objectives
• Understand pain and quality of life in
patients with SCD
• Understand the results of PISCES study
• Be aware of the bias and stigma
associated with pain treatment
• Understand the problems faced by
people with chronic pain in SCD
• Be aware of the standard of care for
management of pain in SCD.
Pain in Sickle Cell Disease
• Hallmark of disease
• Ischemic
• Secondary to erythrocyte (at
minimum, rather than platelet)
vaso-occlusion
• Ubiquitous
• Present throughout life
Pain in Sickle Cell
Disease
• Poorly understood
• Variable
• Genotype and biological traits
explain only part of these
variances
• Little is known about differences
in pain responses
Pain rate above age of 20
is predictor of death
r<1
1<r<3
r>3
Survival probability
1.2
1
0.8
0.6
0.4
0.2
0
20
30
40
Age
50
• Adapted
from: Platt,
et.al. N Engl
J Med;
1991;325:11
-16.
Visits of Variable Frequency
• Unpredictable (within patient)
• 40% of patients with less than 1 ED/hospital
visit/year
• Small number of patients (5%) responsible for large
number of visits (40%)
• Hemoglobin type predicts visit frequency
– Hemoglobin SS 0.8/year
– Hemoglobin SC, S b Thal 0.4/year
– More Hemoglobin F, fewer a hemoglobin chain genes
decreases frequency
• Platt, et.al. N Engl J Med; 1991;325:11-16
Psychosocial variables
•stress
•mental health status
•coping behaviors
•social support
•personality
Demographics
Illness related variables
•genotype
•hematologic measures
•medical complications
•comorbidity
•treatment
Adapted from: Reese FL, Smith WR. Psycho-social
determinants of health care utilization in sickle cell disease
patients. Ann Behav Med 1997;19(2):171-178.
Cues to Action
•pain perceptions
•concerns of caretakers
Readiness variables
•Perceived threat
•Perceived benefits/barriers to care
Pain, Health
Care
Utilization
Specific Issues in SCD Pain
Interactions: A Vicious Cycle
• Perception of a high prevalence of addiction  inadequate
analgesia.
– 53% of ED physicians , 23% of hematologists said > 20% of adult SCD
“addicted”
– 22% of ED physicians 9% of hematologists said > 50% addicted [22].
• SCD pts may be under-medicated in the ED [25, 26]
– may report more pain and have increased rates of hospital utilization.
• Undertreatment  behaviors of pseudoaddiction
– (drug-seeking behaviors that resolve when pain is adequately treated) which are
often misunderstood and reinforce the misconceptions of addiction [27. ]
• Inadequate analgesia  communication barriers, ↓ trust in the
provider.
– Most patients have had negative experiences in the acute care setting
SCD Health Outlook: Influences on
Pain interactions (more of a Vicious
Cycle)
• Negative attitudesPatients loathe/avoid coming
to busy EDs, treat even severe pain at home.
– Negative attitudes and medical care opinions based on previous
experiences [28].
– Pts report being treated rudely, or delays, avoid the ED until
extreme need provokes utilization [27, 29].
• Documented disputes between patients and staff
about patient behaviors that raised staff concerns
about analgesic misuse. [30]
• SCD pts rate satisfaction / humaneness of care
significantly << asthma pts. [29]
Definitions
• Tolerance = Decreased analgesic
response to same dose of drug
– may be perceived as true addiction
– Earliest symptom is shortening of duration of effective
analgesia
• Physical dependence = Production of
withdrawal upon abrupt discontinuation,
antagonist
• Addiction = Psychological dependence
– manifested by dose escalation, use of opioids for
purposes other than pain relief
Pharmacokinetics vs.
Pharmacodynamics
• Pharmacokinetics: drug dose --> drug
concentration
• Pharmacodynamics: drug concentration
--> drug effects (e.g. analgesia)
–
–
–
–
Sigmoid curve
Cf50 = half-maximal concentration
SF effect = effect from half-maximal concentration
Tailor infusions by measuring and aiming for target
concentrations
Dose--> concentration-->
effect
• Pharmacodynamic studies
(relationship between dose,
concentration, effect) not well
done in sickle cell disease
• Correlation between pain relief
and sedation
– On average, but NOT ALWAYS
PiSCES: Number of
Diaries Submitted
• 29,839 submitted diaries
• 141 pts. (62%) submitted
>70% of diaries
• Pain on 16,586 diaries
(55.6%)
• Crisis on 4,429 diaries
Pain Frequency: Histogram
35
96-100
30
25
% Pts
20
15
10
76-95
26-50
11-25
51-75
≤5
6-10
5
0
Percent Days in Pain
• 30% of subjects had pain nearly every day
• Only 13% of subjects almost never had pain
The Iceberg: Proportion of
Days in Pain, Crisis,
Utilization
Intensity
Above
water
Submerged
Utilization
6.5
2.3
Crisis w/o utilization 5.5
2.1
3.5%
13.1%
39.3%
44.1%
Mean Std
Dev
Pain w/o crisis, util.
No Pain
*Percentage of days. Utilization= utilization with or without crisis or pain;
Crisis= crisis without utilization; Pain= pain without crisis or utilization
Adapted from Smith WR, et. al. Ann Intern Med 2008 Jan 15, 148(2):94-101
4.2
2
0
0
M
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ea
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ta
R
ol
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a
Bo
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en
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Ph
y
lF
R
ol
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Ph
y
Mean subscale scores SF 36
Quality of Life, Sickle vs. Chronic
Diseases
90
80
70
60
50
40
30
20
10
0
PISCES
Asthma
Cystic fibrosis
Dialysis
Depression, Alcohol,
Anxiety
• Any depression 28.3%
• Major depression 14.9%
• Other depression 13.6%
• Any anxiety disorder 8.9%
• Panic disorder 4.4%
• Other anxiety 3.5%
• 70% with anxiety also had depression
• Alcohol abuse 31.4%
Summary of Findings:
Pain, Crises, And
Utilization In Sickle Cell
Disease
• 55% of patients had pain on
more than half of their diary
days
• 30% had pain essentially daily
• 4,429 crisis days (14.8%)
• In contrast, patients reported
only 1,057 utilization days
Conclusions
• Pain in sickle cell disease is the rule
rather than the exception.
• (Severe) sickle cell pain occurs on a much
higher proportion of days than previously
reported
– Much of sickle cell pain is not called a “crisis” by
patients.
– Utilization is the exception rather than the rule for
response to pain in sickle cell disease.
Conclusions
• The largely “submerged” iceberg of pain
in SCD is not seen by most caregivers,
but is managed outside medical
facilities.
– Most sickle cell pain, though severe, is not
severe enough to be called “crisis” pain
– Most crises are not associated with
utilization
Implications of PiSCES and
other Research
• The term “crisis,” as used by patients
experiencing SCD pain, has a complex
meaning
– very different from utilization or presence of pain
– radically different from health care workers’ traditional
meaning
• Current pain terminology and measurement
in sickle cell disease management may
lead to:
– Misclassification
– Distorted Communication
The term “Crisis”
• Good because it emphasizes the
need for aggressive pain
management
• Bad because it may be misleading
– “Crisis” More prevalent than utilization
– “Crisis” Less prevalent than pain
– “Crisis” radically different from health care
workers’ traditional meaning (utilization)
The Term “Chronic Pain
Syndrome”
• May be accurate for some
– Communicates high prevalence of pain
• May be misleading
– Seems to be used to describe high utilizers
– High prevalence of pain applies to most patients!
– Patients who are not high utilizers may still need
aggressive daily pain management
– Distinguishing lower- from higher-utilizing SCD
patients may be misleading because they may
have equal pain.
A Model of Chronic Pain in
SCD
10
9
8
7
Pain Severity
6
Nociceptive Ischemia
5
Nociceptive Necrosis
Central Sensitization
4
3
2
1
0
1
6
11
16
21
26
31
Age
36
41
46
51
56
61
Trust the SCD Patients’
Report of Pain
• 3.5% utilization days vs 56%
pain days!
Pain Management of
Acute Vaso-occlusive
Episodes
ED Management
• Parenteral narcotics usually
• AVOID DEMEROL
– Seizures (nor-meperidine, toxic metabolite)
• If comfortable 3-4 hours, try oral
narcotic and observe
• If pain returns, repeat parenteral
narcotic
• Admit if pain persists after this
• When pain controlled, give adequate
Inpatient Management
• PCA or fixed schedule, not p.r.n.
– Avoid basal rate, or hold fixed dose if patient asleep
– Reevaluate dose q 24 hours
• When tapering dose, don't stretch interval
• Go oral when tolerated 50% decrease
parenteral
• Adjust oral dose to provide equivalent
analgesia
– Let patient and nurse participate in decisions
• Use potentiators in selected patients
Patient-controlled
analgesia
• ED, Inpatient tool
• Decreases total opioid requirement in
sickle cell patients
• Increases patient satisfaction
•
•
•
Holbrook C T. J Assoc Acad Minor Phys 1990; 1(3): 936.
McPherson E, Perlin E, Finke H, Castro O, Pittman J.
Am J Med Sci 1990;299: 10-2.
Gonzalez E R. Bahal N. Hansen L A. Ware D. Bull D S.
Ornato J P. Lehman M E. Arch Intern Med 1991 Jul;
151(7): 1373-8.
•
•
•
•
•
•
•
•
Acute Episode
Management
Hydrate
Oxygen unnecessary unless % sat <90
Saline, not D5W
Provide adequate analgesia
Investigate cause of pain
Titrate analgesics
Avoid transfusion
Learn patient’s usual pattern of pain
Promise and Provide
Adequate Analgesia
• Breake the vicious cycle of
pain-distress-pain
• Patients may not trust at first
Individualize Treatment
– Individualize analgesic dose and
frequency based on pharmacokinetic
and pharmacodynamic principles
Titrate the Opioid Dose
ANALGESIA
8mg 12mg 16 mg
SF effect
• Pharmacodynami
c Curve,
Tolerance Greatly
Affect opioid
Requirements
• TITRATE,
TITRATE,
TITRATE!!!
Cf50
Narcotic DOSE
Add Long-Acting Opioids to
Breakthrough Short-Acting Opioids
in Patients with Chronic (Relapsing)
Pain
• Controlled release morphine vs.
intramuscular meperidine and shortacting oral opioids
– Decreased utilization
•
•
•
•
•
Admissions
44%
(Still lower 1 year later)
Inpatient days57%
Length of stay23%
Emergency visits
67%
Similar decreases for 15 high utilizers
– Brookoff D. Polomano R. Treating sickle cell pain like cancer pain.
Ann Intern Med 1992 Mar 1; 116(5): 364-8.
Summary, Opioids and Sickle
Cell Disease in Adults
• Most do not require daily opioid maintenance
• Many may be tolerant to opioids because
they’ve been on them for years
• Some may become dependent on opioids
given daily for long periods
• Most are not addicted to opioids
• Most do not abuse drugs
• Street drug abuse is possible, should screen,
will not offend non-abusers
• Safe use of LARGE QUANTITIES of opioids
is possible with contracts and good recordkeeping
Non-opioid analgesia for
mild pain
• Acetaminophen
– Aspirin may cause hyperuricemia
– Use with caution in chronic renal
failure
– In high doses causes hepatic damage
• Non-steroidals
– Very useful for avascular necrosis
– may cause peptic ulcers