Circulation

ORIGINAL RESEARCH ARTICLE

Persistent Opioid Use After Cardiac Implantable

Electronic Device Procedures
Timothy M. Markman , MD; Chase R. Brown, MD; Lin Yang , MS; Gustavo S. Guandalini , MD;
Matthew C. Hyman , MD, PhD; Jeffrey S. Arkles , MD; Pasquale Santangeli, MD; Robert D. Schaller, DO;
Gregory E. Supple, MD; Rajat Deo, MD; Saman Nazarian , MD, PhD; Sanjay Dixit , MD; David J. Callans, MD;
Andrew E. Epstein , MD; Francis E. Marchlinski, MD; Peter W. Groeneveld , MD; David S. Frankel , MD

BACKGROUND: Prescription opioids are a major contributor to the ongoing epidemic of persistent opioid use (POU). The
incidence of POU among opioid-naïve patients after cardiac implantable electronic device (CIED) procedures is unknown.

METHODS: This retrospective cohort study used data from a national administrative claims database from 2004 to 2018 of
patients undergoing CIED procedures. Adult patients were included if they were opioid-naïve during the 180-day period
before the procedure and did not undergo another procedure with anesthesia in the next 180 days. POU was defined by
filling an additional opioid prescription >30 days after the CIED procedure.

RESULTS: Of the 143 400 patients who met the inclusion criteria, 15 316 (11%) filled an opioid prescription within 14 days
of surgery. Among these patients, POU occurred in 1901 (12.4%) patients 30 to 180 days after surgery. The likelihood
of developing POU was increased for patients who had a history of drug abuse (odds ratio, 1.52; P=0.005), preoperative
muscle relaxant (odds ratio, 1.52; P<0.001) or benzodiazepine (odds ratio, 1.23; P=0.001) use, or opioid use in the previous
5 years (OR, 1.76; P<0.0001). POU did not differ after subcutaneous implantable cardioverter defibrillator or other CIED
procedures (11.1 versus 12.4%; P=0.5). In a sensitivity analysis excluding high-risk patients who were discharged to a facility
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or who had a history of drug abuse or previous opioid, benzodiazepine, or muscle relaxant use, 8.9% of the remaining cohort
had POU. Patients prescribed >135 mg of oral morphine equivalents had a significantly increased risk of POU.

CONCLUSIONS: POU is common after CIED procedures, and 12% of patients continued to use opioids >30 days after surgery.
Higher initially prescribed oral morphine equivalent doses were associated with developing POU.

Key Words: analgesics, opioid ◼ defibrillators, implantable ◼ pacemakers

Editorial, see p 1598

T
he ongoing epidemic of prescription opioid abuse
in the United States is attributable in part to exces-
sive prescription of opioid pain medication. The over-
prescription of opioids is multifactorial, related to patient
expectations regarding pain control, provider attitudes, and
external factors including the evaluation of pain as a vital
sign.1,2 This has contributed to a steadily increasing number
of drug overdoses in the United States, reaching an all-time
high of 90 000 in 2020.3–5 In addition, morbidity associ-
ated with addiction to and overdose of opioids has caused
a substantial economic burden.6–8 Rates of opioid-related
death in the United States are 7-fold greater than in West-
ern Europe, where the incidence of chronic pain is similar.9,10
Six times as many opioid prescriptions are filled per person
in the United States than in France.11
In October 2017, the US Department of Health and
Human Services declared a Public Health Emergency to
address the national opioid crisis. That year, 191 909 384
opioid prescriptions were dispensed in the United States,
a rate of 59 prescriptions per 100 persons.5 Because of

Correspondence to: David S. Frankel, MD, Hospital of the University of Pennsylvania, 3400 Spruce Street, 9 Founders Pavilion, Philadelphia, PA 19104. Email david.
frankel@pennmedicine.upenn.edu
Continuing medical education (CME) credit is available for this article. Go to http://cme.ahajournals.org to take the quiz.
For Sources of Funding and Disclosures, see page 1597.
© 2021 American Heart Association, Inc.
Circulation is available at www.ahajournals.org/journal/circ

1590 November 16, 2021 Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524

 Markman et al
Clinical Perspective
What Is New?
• Persistent opioid use is common after cardiac
implantable electronic device procedures, occur-
ring in ≈12% of patients who fill an opioid prescrip-
tion after their surgery.
• Higher prescribed doses of opioids after the device
procedure are strongly associated with subsequent
persistent opioid use.
What Are the Clinical Implications?
• All physicians who perform cardiac implantable elec-
tronic device procedures and care for these patients
should be aware of the risk of persistent opioid use.
• Postoperative opioid use should be limited using
a multimodality approach including patient educa-
tion, procedural strategies such as peripheral nerve
blocks, and use of nonopioid analgesics.
Nonstandard Abbreviations and Acronyms
CIED cardiac implantable electronic device
CPT current procedural terminology
OME oral morphine equivalent
POU persistent opioid use
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the increased recognition that opioid prescriptions have
the potential for harm, there has been enhanced scru-
tiny into the use of opioids after major and minor surgi-
cal procedures. Persistent opioid use (POU) has been
reported in up to 10% of patients after general surgery
procedures, and a recent study identified a similar rate of
POU in a large population after cardiac surgery.12,13 This
consistent risk of POU has led to advocacy for the limited
use of postsurgical opioids and consideration for nonopi-
oid analgesic strategies.14–16 The role of opioid prescrip-
tions after cardiac implantable electronic device (CIED)
procedures has been examined in a retrospective series
from a single heath system that suggested that nearly
10% of opioid-naïve patients subsequently refilled opioid
prescriptions.17 No large national population studies have
characterized the use of opioids after CIED procedures
or have evaluated the risk of POU in this population.
To determine the incidence of and risk factors for
POU, this study aimed to evaluate patients undergoing
CIED procedures in a large, national administrative data-
base who were prescribed opioids on discharge.
METHODS
Data Source
Data were obtained from the Optum deidentified Clinformatics
Data Mart, a database of administrative health claims for
Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524
Opioid Use After CIED Procedures
members’ commercial and Medicare Advantage health plans.
Administrative claims submitted for payment are verified, adju-
ORIGINAL RESEARCH
dicated, and deidentified before inclusion in the Clinformatics
Data Mart. The database consists of comprehensive medical
ARTICLE
claims for ≈15 million annual covered lives spanning throughout
the United States and includes member eligibility, demograph-
ics, and socioeconomic data available through zip code linking
from the US Census Bureau. The Optum database comprises
a geographically, racially, and ethnically diverse population. The
data used for this study are the property of Optum and were
used by the investigators through a contractual agreement.
Inquiries about obtaining similar data can be directed to Optum
at https://www.optum.com/solutions/life-sciences/life-sci-
ences-contact.html. The University of Pennsylvania Institutional
Review Board determined that this research was exempt from
the regulatory requirements of the federal Common Rule.
Study Cohort
We identified adult patients who underwent a CIED procedure
from January 1, 2004, to December 31, 2018. Cardiac device
procedures were identified using Current Procedural Terminology
(CPT) codes and included implantation, revision, extraction, or
generator change for all pacemakers or implantable cardioverter
defibrillators, excluding leadless pacemakers. If patients had mul-
tiple procedures while in the Optum database, only the first proce-
dure was analyzed. The cohort consisted of opioid-naïve patients,
as defined by lack of prescribed opioids within 180 days before
their CIED procedure, but who filled an opioid prescription within
14 days after their procedure. Remote opioid prescriptions filled
between 5 years and 180 days before the procedure were evalu-
ated as a risk factor for developing POU after the CIED proce-
dure. Patients were excluded if they had a preoperative diagnosis
of metastatic cancer or if they underwent any repeat device or
anesthesia procedure during the subsequent 180 days, given that
these procedures could result in additional opioid prescriptions.
Prescriber specialty was identified on the basis of the National
Provider Identifier number associated with the prescription.
Opioids included any drug containing oral hydrocodone,
oxycodone, tramadol, codeine, hydromorphone, morphine,
tapentadol, oxymorphone, or transdermal fentanyl. The initial
postprocedural opioid prescription (prescribed dose multiplied
by total number of pills) was converted to oral morphine equiva-
lents (OMEs), which standardizes each opioid drug to an equiv-
alent dosage.13,18 POU was defined by a patient filling an opioid
prescription within the first 14 days after the index procedure
and then filling another opioid prescription within 30 to 180
days after the procedure. This definition was chosen based on
a previous publication on POU after cardiac surgery, which was
defined by filling a second opioid prescription within 90 to 180
days.13 Compared with cardiac surgery, acute procedural pain
would be expected to resolve more quickly after CIED proce-
dures. Opioid prescriptions filled beyond 30 days are unlikely to
have been prescribed for treatment of procedural pain alone.
Procedural complications including pneumothorax, hematoma,
cardiac perforation, or pericarditis were identified on the basis
of International Classification of Diseases codes.
Statistical Analysis
The primary outcome of this study was the percentage
of patients who had POU 30 to 180 days after the index
November 16, 2021 1591
 Markman et al
procedure. The secondary outcome was the percentage of
patients who had POU 180 to 270 days after the index pro-
ORIGINAL RESEARCH
cedure. For these outcomes, patients who underwent any
repeat device or anesthesia procedure were excluded. Baseline
ARTICLE
demographic characteristics, medical comorbidities, medica-
tions, procedural characteristics, and discharge OMEs were
tested for association with subsequent development of POU.
Differences in characteristics and outcomes between groups
were compared using χ2 tests for categorical variables and
analysis of variance for continuous variables. We performed
adjusted logistic regression to determine patient factors that
were associated with POU, excluding collinear variables with
ρ>0.3. We used cubic splines to determine the nonlinear asso-
ciation of OMEs prescribed at discharge with the odds of POU.
Knots were determined using the quartiles of OMEs prescribed
(90 mg, 135 mg, 180 mg). All statistical tests were 2-sided,
with P<0.05 indicating significance.
RESULTS
Of the 242 360 patients who underwent a CIED proce-
dure during the study period, 143 400 were eligible for
inclusion (Figure 1). Of these 143 400 patients, 30 660
(21%) had filled an opioid prescription in the preced-
ing 5 years and 15 316 (11%) patients filled an opioid
prescription within 14 days after their procedure. The
percentage of patients filling opioid prescriptions rose
steadily over the study period (P<0.0001; Figure 2). Af-
ter October 2017, when a public health emergency was
declared in the United States, 16 494 procedures were
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Figure 1. Patient inclusion and flow.
Persistent opioid use is identified on the basis of filled opioid prescriptions 30 to 180 days after cardiac implantable electronic device procedures.
POU indicates persistent opioid use.
1592 November 16, 2021
Opioid Use After CIED Procedures
performed; among these, 2350 (14%) patients filled an
opioid prescription in the subsequent 14 days, a rate sim-
ilar to that observed in the immediately preceding years.
Among those patients who filled prescriptions, the me-
dian OME dose decreased from 150 mg in 2004 to 100
mg in 2018 (P<0.0001).
Among the 15 316 patients who filled an index opi-
oid prescription within 14 days of their surgery, 4800
(31%) patients had filled a previous opioid prescription.
A total of 367 (2%) underwent subcutaneous implant-
able cardioverter defibrillator procedures. Complications
were noted in 1% of patients, including pneumothorax
(0.1%), hematoma (0.4%), cardiac perforation (0.7%),
and pericarditis (0.3%). Table 1 presents the patient
characteristics and demographic data stratified by
development of POU.
We determined the portion of patients who had POU
during the period 30 to 180 days and 180 to 270 days
after the index procedure. Overall, 1901 (12.4%) patients
had POU within 30 to 180 days. From 180 to 270 days
postoperatively, 14 470 patients were eligible for analy-
sis after excluding patients who underwent another pro-
cedure during this time period. Of these patients, 1075
(7.4%) had POU. Among the 128 084 patients who did
not fill an initial opioid prescription within 14 days after
their CIED procedure, 6928 (5.4%) filled an opioid pre-
scription within 30 to 180 days after their procedure.
Patients with POU after the index opioid prescription
were older (69 versus 67 years; P<0.0001), more likely
Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524
 Markman et al
Figure 2. Rate of opioid prescriptions filled within 14 days of index cardiac implantable electronic device procedures and
median OME prescribed from 2004 to 2018.
OME indicates oral morphine equivalent.
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to be female (47% versus 39%; P<0.0001), and more
likely to have a history of depression (21% versus 16%;
P<0.0001), alcoholism (5% versus 4%; P=0.03), drug
abuse (4% versus 2%; P<0.0001), or psychosis (9% ver-
sus 6%; P<0.0001). There was no significant difference
in the rate of POU between patients who underwent a
subcutaneous implantable cardioverter defibrillator ver-
sus other CIED procedure during either 30 to 180 days
(11.2% versus 12.4%; P=0.5) or 181 to 270 days (7.0%
versus 7.4%; P=0.8) after their procedure. Cardiologists
or cardiothoracic surgeons wrote 45% of initial opioid
prescriptions but only 4% of opioid prescriptions that
were filled during the 30- to 180-day period.
There was a direct, nonlinear association between the
OMEs initially prescribed and the likelihood of developing
POU (Figure 3). The median OME at discharge of 135
mg (interquartile range, 90–180 mg), or 18 tablets of
oxycodone 5 mg, was defined as the reference. Patients
who were prescribed >135 mg of OME after their proce-
dure had significantly increased risk for developing POU
compared with patients prescribed <135 mg of OME
(odds ratio [OR], 1.96; P<0.0001). Using adjusted logistic
regression, we found that male patients (OR, 0.77 [0.69–
0.85]; P<0.001) and patients discharged to home (OR,
0.76 [0.59–0.97]; P=0.03) were less likely to develop POU
(Table 2). We found that patients with comorbidities includ-
ing chronic pulmonary disease (OR, 1.22 [1.140–1.36];
Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524
Opioid Use After CIED Procedures
ORIGINAL RESEARCH
ARTICLE
P=0.0002), diabetes (OR, 1.15 [1.04–1.29]; P=0.008),
rheumatic disorders (OR, 1.33 [1.11–1.58]; P=0.001), and
history of drug abuse (OR, 1.52 [1.13–2.01]; P=0.005)
were more likely to develop POU. Preoperative use of
muscle relaxants (OR, 1.52 [1.18–1.95]; P=0.001) and
benzodiazepines (OR, 1.28 [1.09–1.49]; P=0.002) were
also associated with increased risk of POU. Opioid use
in the 5-year period before the index procedure was also
associated with POU (OR, 1.76 [1.58–1.97]; P<0.0001).
Procedural complications, including pneumothorax, hema-
toma, cardiac perforation, or pericarditis, were not associ-
ated with development of POU.
To determine whether the results of this study would
apply to low-risk patients after CIED procedures, we cal-
culated the incidence of POU after surgery after exclud-
ing patients at highest risk on the basis of preoperative
use of benzodiazepines (9%) or muscle relaxants (3%),
history of drug abuse (2%) or opioid use in the preced-
ing 5-year period, and those discharged to a facility after
surgery (2%). Among the remaining cohort of 9039
patients presumed to be at low risk, POU developed in
8.9% within 30 to 180 days after the procedure.
DISCUSSION
In this cohort of privately managed health insurance pa-
tients, we found that opioid use after CIED procedures
November 16, 2021 1593
 Markman et al Opioid Use After CIED Procedures

Table 1. Patient Demographics, Comorbidities, Medications, Table 1. Continued

and Procedural Characteristics, by Persistent Opioid Use
ORIGINAL RESEARCH

Persistent opioid use

Persistent opioid use
All No Yes
ARTICLE

All No Yes Characteristics (n=15 316) (n=13 415) (n=1901)

Characteristics (n=15 316) (n=13 415) (n=1901)
Complications
Age, y 67.4 (13.8) 67.2 (14.0) 68.9 (12.7) Pneumothorax 12 (0.1) 11 (0.1) 1 (0.1)
Men 9237 (60) 8235 (61) 1002 (52.7) Hematoma 54 (0.4) 43 (0.4) 11 (0.8)
White 10 160 (66) 8924 (67) 1236 (65) Cardiac perforation 122 (0.7) 109 (0.7) 13 (0.7)
Bachelor degree or higher 1746 (11) 1562 (12) 184 (10) Pericarditis 37 (0.3) 32 (0.3) 5 (0.3)
Income >$100 000 2537 (17) 2274 (17) 163 (14) Hospital course
Year Discharge to home 14 821 (97) 13 011 (97) 1810 (95)
2004 to 2008 2182 (14) 1950 (15) 232 (12) Length of stay, d 2.0 (4.9) 1.9 (4.9) 2.6 (4.7)
2009 to 2013 4936 (32) 4342 (32) 594 (31)
All variables signify percentages, except age and length of stay, which
2014 to 2018 8198 (54) 7123 (53) 1075 (57) signify standard deviations.
Region
Midwest 3515 (23) 3112 (21) 403 (21)
more than doubled between 2004 and 2018. Among
patients with initial opioid use, POU frequently results
Northeast 1116 (7) 996 (7) 120 (6)
(12.4% versus only 5.4% of patients without an initial
South 7904 (52) 6875 (51) 1029 (54)
opioid prescription). The higher the dose of initially pre-
West 2732 (18) 2391 (18) 341 (18) scribed opioids, the more likely POU is to occur.
Comorbidities Recently, Lee et al17 performed an analysis of POU
Hypertension 12 358 (81) 10 739 (80) 1619 (85) after CIED procedures from a single health care sys-
Congestive heart failure 8016 (52) 6955 (52) 1061 (59) tem and found that ≈10% of patients prescribed opioids
 Pulmonary circulation 1516 (10) 1299 (10) 217 (11)
went to on develop persistent use. Our study confirms
disorders these findings using a database that includes >10-fold
 Chronic pulmonary dis- 5288 (35) 4463 (33) 825 (43) as many patients, is geographically diverse, and excludes
ease patients who underwent another anesthesia procedure
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Diabetes 5810 (38) 4968 (37) 842 (44) during the follow-up period. This is the most definitive
 Peripheral vascular dis- 4263 (28) 3615 (27) 648 (34) evidence to date that opioid prescriptions after CIED
ease procedures commonly lead to POU.
Kidney disease 3216 (21) 2729 (20) 487 (26) The observed rate of POU is also consistent with stud-
Liver disease 893 (6) 748 (6) 145 (8) ies in a variety of surgical procedures ranging from minor,
Obesity 3426 (22) 2942 (22) 484 (26)
minimally invasive procedures to major abdominal or thoracic
surgery.7,13 Reinforcing the concept that the scale of the sur-
Weight loss 1119 (7) 921 (7) 198 (10)
gical procedure and associated pain is not the main factor
 Chronic blood loss 455 (3) 379 (3) 76 (4)
that determines POU, we observed no significant difference
anemia
in the rate of POU among patients who underwent subcu-
Deficiency anemias 4104 (27) 3464 (26) 640 (34)
taneous implantable cardioverter defibrillator procedures
Paralysis 480 (3) 392 (3) 88 (5)
(11.2% versus 12.4% for all patients), which is often a pain-
Neurologic disorders 2311 (15) 1960 (15) 351 (19) ful procedure involving extensive tissue dissection.
Rheumatic disorders 996 (7) 798 (6) 198 (10) We found that the initially prescribed opioid dose
 Fluid and electrolyte 4298 (28) 3613 (27) 685 (36) strongly predicted subsequent development of POU.
disorders Prescriptions of >135 mg OME were significantly asso-
Depression 2508 (16) 2108 (16) 400 (21) ciated with an increased risk. This dose is substantially
Alcoholism 590 (4) 500 (4) 90 (5) lower than the OME prescription associated with POU
Drug abuse 318 (2) 245 (2) 73 (4) after cardiac surgery.13 This suggests that after minor
Psychoses 977 (6) 807 (6) 170 (9)
procedures patients may be particularly susceptible to
developing POU even when lower initial opioid doses
Preoperative medication use
are prescribed. It is therefore critical for physicians to
Muscle relaxant 411 (3) 322 (2) 89 (5)
understand that the risk of opioid dependence exists
Benzodiazepine 1403 (9) 1167 (9) 236 (12) even with minor procedures and that excessive opioid
Antipsychotic 222 (1) 175 (1) 27 (3) doses increase the risk of subsequent dependence.
 Opioid in preceding 4800 (31) 3923 (29) 877 (46) These results support the use of lower opioid doses at
5-year period discharge as well as increasing use of alternative pain
(Continued ) management strategies.

1594 November 16, 2021 Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524

 Markman et al
We identified several additional factors associated
with opioid dependence. Patients who were female, had
increased preoperative comorbidities (eg, chronic pulmo-
nary disease, diabetes, rheumatic disorders), had preop-
erative drug abuse, or were taking muscle relaxants or
benzodiazepines preoperatively were all at increased risk
for POU. This was also the case for patients filling opi-
oid prescriptions in the preceding 5 years or those who
were discharged to a facility and those with increased
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length of stay in the hospital during their index proce-
dure. Although it is important to recognize that certain
patients may be at particularly high risk, even when the
highest risk patients were excluded from the analysis, the
incidence of POU remained 8.9% in the 30 to 180 days
after the procedure. Therefore, prescribers should con-
sider all patients to be at risk for development of POU
and should take steps to decrease the use of opioids
postprocedurally.
The rate of opioid prescriptions written by prescribers
in specialties that perform CIED procedures decreased
from 45% for the initial prescription to 4% during the
30- to 180-day period. Although the characterization of
prescriber specialty associated with National Provider
Identifier codes is incomplete, this marked reduction
strongly suggests that a substantial proportion of POU
may not be coming to the attention of the physicians who
performed the procedure. Therefore, it is critical that all
physicians, including those implanting CIEDs and those
providing other longitudinal care to these patients, be
aware of this risk and minimize the use of opioids.
Despite the declaration of a public health emergency
by the Department of Health and Human Services in
2017, our data do not suggest that practice patterns suf-
ficiently changed during the period of follow-up included
in this study. Our data include only a limited time period
after this declaration and it remains possible that prac-
tice patterns have evolved since that time. Although the
Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524
Opioid Use After CIED Procedures
ORIGINAL RESEARCH
Figure 3. Association of the OMEs of
first prescription filled postprocedure
ARTICLE
with the likelihood of developing
persistent opioid use.
An oral morphine equivalent (OME) of
135 mg (the median OME prescribed)
was used as the reference point. Patients
who were prescribed >135 mg OME
(≈18 tablets of oxycodone 5 mg) had
an increased likelihood of developing
persistent opioid use. OMEs are defined
as the total number of opioid tablets
dispensed multiplied by the dosage and
the morphine conversion factor. Persistent
opioid use is defined by filling an opioid
prescription within 30 to 180 days after
surgery. The shaded area of the figure
represents the 95% CI of the odds ratio.
median OME prescribed has been declining since 2013,
the rate of opioid prescriptions filled after CIED implanta-
tions has remained stable in recent years. This highlights
the critical importance of continued emphasis on reduc-
tion in opioid prescriptions as well as OME prescribed
among the patients who require opioids in the immediate
postprocedure period.
Multiple strategies have been demonstrated to
decrease the need for postoperative opioids, includ-
ing preoperative and postoperative use of nonopioid
analgesics such as acetaminophen, nonsteroidal anti-
inflammatory drugs, and gabapentin (Table 3). Combining
these agents often results in synergistic analgesia.19,20
Intraprocedural use of long-acting local anesthetics and
peripheral regional nerve blockade can greatly improve
postoperative pain.21–23 Alternative strategies, such as
tumescent local anesthesia, are also promising and
should be considered especially in high-risk patients.24
Patient education is critical so that patients anticipate
a brief period of pain after their procedure and follow
appropriate arm restrictions in the immediate postopera-
tive period to reduce the risk of lead dislodgement but
avoid prolonged, excessive immobilization, which can
lead to adhesive capsulitis.
Limitations
This is an observational study that used an adminis-
trative database and is subject to errors in coding and
misclassification. We were unable to identify opioid
prescriptions written but not filled by patients, filled by
patients using a different pharmacy benefit, or paid for
out of pocket, potentially underestimating total pre-
scription rates. In addition, this database consists of
adults with private insurance or Medicare-managed
coverage and may not be generalizable to other popu-
lations. Complications were identified on the basis of
November 16, 2021 1595
 Markman et al Opioid Use After CIED Procedures

Table 2. Risk Factors for Developing Persistent Opioid Use Table 3. Strategies to Reduce the Need for Opioids After
30 to 180 Days After Device Procedures Among Patients Cardiac Implantable Electronic Device Procedures
ORIGINAL RESEARCH

Filling an Index Opioid Prescription Within 14 Days

Patient education,
strategies, and
ARTICLE

Adjusted odds ratio

Characteristics (95% CI) P value approaches Details

Age (per 5-year increase) 1.02 (1.00–1.04) 0.04 Patient education

Male 0.77 (0.69–0.85) <0.001 Expectations of pain Patients should be counseled to expect pain at
the surgical sites. They should be reassured that
White 0.99 (0.88–1.11) 0.9
pain will typically resolve within 5 to 7 days after
Bachelor degree or higher 1.06 (0.55–2.07) 0.9 the procedure.
Income >$100 000 0.92 (0.77–1.11) 0.4  Postprocedural arm It is important to restrict extreme arm movements
restrictions for 4 to 6 weeks to decrease the risk of lead dis-
Region
lodgement, but normal range of arm movements
South Reference should be encouraged the day after the proce-
Midwest 0.96 (0.85–1.09) 0.6 dure to decrease the risk of adhesive capsulitis.

Northeast 0.89 (0.72–1.09) 0.3 Procedural strategies

West 0.94 (0.82–1.08) 0.4 Local anesthesia Adequate infiltration of local anesthetic agents is
critical to improve immediate postoperative pain.
Year of cardiac implantable electronic device procedure Use of long-acting agents, such as liposomal bu-
2004 to 2008 Reference pivacaine, can be considered to extend anesthetic
effect for up to 72 hours.
2009 to 2013 1.09 (0.79–1.50) 0.6
 Regional nerve Truncal plane blocks for subcutaneous implant-
2014 to 2018 1.14 (0.83–1.56) 0.4 block able cardioverter defibrillators and pectoral nerve
Comorbidities blocks for other cardiac implantable electronic
device procedures can minimize the need for in-
Congestive heart failure 0.98 (0.88–1.09) 0.7 traprocedural anesthesia and improve immediate
Pulmonary circulation disorders 0.95 (0.81–1.12) 0.6 postoperative pain.

Chronic pulmonary disease 1.22 (1.10–1.36) 0.0002  Tumescent local Infiltration of a solution containing lidocaine,
anesthesia epinephrine, sodium bicarbonate, and sodium
Diabetes 1.15 (1.04–1.29) 0.008
chloride can reduce the need for intraprocedural
Peripheral vascular disease 1.08 (0.96–1.21) 0.2 anesthesia and reduce postoperative pain.

Kidney disease 1.02 (0.89–1.15) 0.8  Implantation tech- Meticulous procedural technique to avoid compli-
nique cations including hematoma and infection is criti-
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Liver disease 1.08 (0.89–1.32) 0.4

cal. Careful device positioning, to avoid migration
Obesity 1.00 (0.89–1.12) 0.9 into the axilla, will reduce chronic discomfort.
Weight loss 1.13 (0.95–1.35) 0.2 Pharmacologic approaches
Chronic blood loss anemia 0.99 (0.76–1.29) 0.9  Preprocedural an- Preemptive analgesia before the incision can
algesia reduce the sensation of pain after the procedure.
Paralysis 1.24 (0.96–1.59) 0.1
This can include nonopioid agents, which may be
Neurologic disorders 0.97 (0.84–1.10) 0.6 administered 1 to 2 hours before the procedure.
Rheumatic disorders 1.33 (1.11–1.58) 0.001 Nonopioid agents Acetaminophen and nonsteroidal anti-inflam-
Fluid and electrolyte disorders 1.13 (1.01–1.27) 0.05 matory drugs are highly effective at preventing
and treating postoperative pain. Gabapentin
Depression 1.01 (0.89–1.16) 0.8 or pregabalin can be used as well to spare the
Alcoholism 1.18 (0.92–1.50) 0.2 need for opioid analgesics. Multiple classes of
analgesics can be combined, with synergistic
Drug abuse 1.51 (1.13–2.01) 0.005 effects.
Psychoses 1.09 (0.90–1.33) 0.4
Preoperative medication use
International Classification of Diseases codes during
Muscle relaxant 1.52 (1.18–1.95) 0.001
the index admission. Some patients may have devel-
Benzodiazepine 1.28 (1.09–1.49) 0.002
oped complications after hospital discharge, potentially
Antipsychotic 1.45 (1.02–2.06) 0.04
leading to an underestimate of the association between
Opioid in preceding 5-year period 1.76 (1.58–1.97) <0.0001 complications and POU. Prescriber specialty was cat-
Complications (any) 1.01 (0.86–1.19) 0.8 egorized on the basis of self-reported National Provider
Pneumothorax 2.09 (0.73–6.02) 0.2 Identifier taxonomy; this information was unavailable or
Hematoma 1.50 (0.79–2.86) 0.2 incomplete for ≈25% of prescriptions and many pre-
Cardiac perforation 0.98 (0.82–1.17) 0.9 scriptions are likely written by team members such as
Pericarditis 0.71 (0.29–1.72) 0.5
nurse practitioners or physician assistants who may not
have a matching National Provider Identifier taxonomy.
Hospital course
This study may underestimate the risk of POU because
Discharge to home 0.76 (0.59–0.97) 0.03
patients may acquire opioids by alternative sources not
Length of stay, d 1.01 (1.00–1.02) 0.01 captured by this database.

1596 November 16, 2021 Circulation. 2021;144:1590–1597. DOI: 10.1161/CIRCULATIONAHA.121.055524

 Markman et al
CONCLUSIONS
We demonstrated that ≈12% of opioid-naïve patients
who fill a prescription for opioids after a CIED procedure
will develop POU 30 to 180 days afterward. An initial
dose of postoperative opioids >135 OMEs, or 18 tablets
of oxycodone 5 mg, was associated with increased risk
for POU. All physicians who perform and care for patients
after CIED procedures, including primary care provid-
ers, should be aware of the risk of POU. It is critical that
postoperative opioid prescription dose be minimized and
alternative analgesic regimens such as nonopioid pain
medications and peripheral nerve blocks be considered.
ARTICLE INFORMATION
Received May 1, 2021; accepted August 26, 2021.
Affiliations
Cardiovascular Division (T.M.M., G.S.G., M.C.H., J.S.A., P.S., R.D.S., G.E.S., R.D., S.N.,
S.D., D.J.C., A.E.E., F.E.M., D.S.F.), Division of Cardiovascular Surgery (C.R.B.), and
Division of General Internal Medicine (P.W.G.), Perelman School of Medicine at
the University of Pennsylvania, Philadelphia. Center for Cardiovascular Outcomes,
Quality, and Evaluative Research, University of Pennsylvania, Philadelphia (L.Y.,
P.W.G., D.S.F.). Corporal Michael J. Crescenz VA Medical Center, Philadelphia
(R.D., S.D., A.E.E., P.W.G.).
Sources of Funding
This work was supported by the Mark Marchlinski EP Research and Education
Fund.
Disclosures
None.
Downloaded from http://ahajournals.org by on March 1, 2024
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