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Innovative Options for
Managing Postsurgical Pain
(An Online Continuing Education Activity)
An Online Continuing Education Activity
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Grant Funds Provided By
Welcome to
Innovative Options for
Managing Postsurgical Pain
(An Online Continuing Education Activity)
CONTINUING EDUCATION INSTRUCTIONS
This educational activity is being offered online and may be completed at any time.
Steps for Successful Course Completion
To earn continuing education credit, the participant must complete the following steps:
1. Read the overview and objectives to ensure consistency with your own learning
needs and objectives. At the end of the activity, you will be assessed on the
attainment of each objective.
2. Review the content of the activity, paying particular attention to those areas that
reflect the objectives.
3. Complete the Test Questions. Missed questions will offer the opportunity to reread the question and answer choices. You may also revisit relevant content.
4. For additional information on an issue or topic, consult the references.
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Pfiedler Enterprises will maintain a record of your continuing education credits
and provide verification, if necessary, for 7 years. Requests for certificates must
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If you have any questions, please call: 720-748-6144.
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Pfiedler Enterprises, 2101 S. Blackhawk Street, Suite 220, Aurora, Colorado 80014
www.pfiedlerenterprises.com Phone: 720-748-6144 Fax: 720-748-6196
OVERVIEW
Effective postsurgical pain management for all patients is a key component of
perioperative nursing care. This is especially important with today’s challenges of
providing high quality, patient-centered care in the face of declining reimbursement and
other economic initiatives. Because the pain management paradigm has shifted to an
increasing use of multimodal analgesia, the role of local anesthetics has taken on greater
significance. Infiltration of a local anesthetic into the surgical site at the time of wound
closure is one aspect of a multimodal approach in managing postsurgical pain. Recent
advancements have led to the development of a local anesthetic with an extended
duration of action and novel delivery platform, thereby broadening its potential role as a
component of some postsurgical pain management regimens. Therefore, perioperative
nurses should be aware of the innovative options in local anesthetics and delivery systems
that are now available to manage postsurgical pain more effectively. This continuing
nursing education activity will provide a discussion of the significant clinical and economic
considerations of ineffective pain management in the current health care climate. It will
review the problems and limitations of opioid therapy and the pathophysiology of acute
pain. Multimodal analgesia as a key strategy for effective postsurgical pain management
will be discussed. The pharmacodynamics of various agents used in a multimodal pain
management regimen will be reviewed. Finally, a new option for managing postsurgical
pain via infiltration of the surgical site with an innovative local anesthetic and delivery
system, including its benefits as documented in the literature, will be discussed.
LEARNER OBJECTIVES
After completing this continuing nursing education activity, the participant should be able
to:
1. Identify the clinical and economic considerations of ineffective pain management
in today’s health care environment.
2. Explain the pathophysiology of acute pain as it relates to the surgical patient.
3. Describe the pharmacodynamics of local anesthetics.
4. Recognize multimodal analgesia as an effective pain management regimen.
5. Describe innovative options in local anesthetic infiltration for managing
postsurgical pain.
6. Discuss literature findings related to the clinical benefits of liposomal
bupivacaine for surgical wound infiltration.
INTENDED AUDIENCE
This continuing education activity is intended for perioperative registered nurses want
to learn more about a novel local anesthetic and delivery system as a component of a
multimodal analgesia regimen for effective management of postsurgical pain.
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Credit/Credit Information
State Board Approval for Nurses
Pfiedler Enterprises is a provider approved by the California Board of Registered Nursing,
Provider Number CEP14944, for 2.0 contact hours.
Obtaining full credit for this offering depends upon attendance, regardless of circumstances,
from beginning to end. Licensees must provide their license numbers for record keeping
purposes.
The certificate of course completion issued at the conclusion of this course must be retained
in the participant’s records for at least four (4) years as proof of attendance.
IACET
Pfiedler Enterprises has been accredited as an Authorized Provider by the International
Association for Continuing Education and Training (IACET).
CEU Statements
• As an IACET Authorized Provider, Pfiedler Enterprises offers CEUs for its programs
that qualify under the ANSI/IACET Standard.
• Pfiedler Enterprises is authorized by IACET to offer 0.2 CEUs for this program.
Release and Expiration Date:
This continuing education activity was planned and provided in accordance with accreditation
criteria. This material was originally produced in April 2015 and can no longer be used after
April 2017 without being updated; therefore, this continuing education activity expires April
2017.
Disclaimer
Pfiedler Enterprises does not endorse or promote any commercial product that may be
discussed in this activity
Support
Funds to support this activity have been provided by Pacira Pharmaceuticals, Inc.
Authors/Planning Committee/Reviewer
Rose Moss, MN, RN, CNOR
Nurse Consultant/Author
C & R Moss Enterprises
Casa Grande, AZ
Judith I. Pfister, RN, BSN, MBA
Program Manager/Planning Committee
Pfiedler Enterprises
Aurora, CO
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Expert Reviewer:
Julia A. Kneedler, RN, MS, EdD
Program Manager/Reviewer
Pfiedler Enterprises
Aurora, CO
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for Those in a Position to Control Content for this
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external interests or influences pose potential bias in content, recommendations or
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pfiedlerenterprises.com/disclosure
Disclosure includes relevant financial relationships with commercial interests related to
the subject matter that may be presented in this continuing education activity. “Relevant
financial relationships” are those in any amount, occurring within the past 12 months
that create a conflict of interest. A commercial interest is any entity producing, marketing,
reselling, or distributing health care goods or services consumed by, or used on, patients.
Activity Authors/ Planning Committee/Reviewer
Rose Moss, RN, MN, CNOR
No conflict of interest
Judith I. Pfister, MBA, RN
Co-owner of company that receives grant funds from commercial entities
Julia A. Kneedler, EdD, RN
Co-owner of company that receives grant funds from commercial entities
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INTRODUCTION
Pain is a predictable consequence of surgery; left untreated, it is associated with
significant physiological, emotional, mental, and economic consequences.1 Over 90 million
surgical procedures are performed annually in the United States; of these, approximately
35 million are ambulatory procedures and 56 million are inpatient procedures.2 Patients
report that some of the most painful surgical procedures are intrathoracic, gastric,
and abdominal surgeries, with pain that lasts from two to eight days.3 A national
study assessing patients’ postoperative pain experience and the status of acute pain
management found that approximately 80% of the patients surveyed experienced acute
postsurgical pain, with most patients reporting moderate, severe, or extreme pain.4
One of the expected outcomes for all surgical patients is that they demonstrate and/or
report adequate pain control, since comfort and pain relief are critical factors in a patient’s
recovery from anesthesia and surgery.5 Therefore, effective postsurgical pain management
is an essential component of perioperative nursing care.
While opioid therapy has been the cornerstone of most postsurgical analgesic regimens,
recent evidence has supported the use of multimodal therapy as a way to decrease
opioid usage, minimize its concomitant opioid-related adverse events, and also improve
economic outcomes.6 One component of a multimodal approach to effective postsurgical
pain management is the use of an extended-release formulation of liposomal bupivacaine
infiltrated into the surgical site at the end of a surgical procedure.
CLINICAL AND ECONOMIC CONSIDERATIONS OF INEFFECTIVE PAIN
MANAGEMENT
Patients report high levels of dissatisfaction when they experience moderate to severe
postsurgical pain.7 It is important to remember that patients’ experiences with pain in
the immediate postoperative period and through recovery can influence their overall
satisfaction with the surgical experience and hospitalization as a whole.8 This takes on
even greater significance in today’s dynamic health care environment. The clinical and
economic considerations related to ineffective pain management are discussed below.
Clinical Consequences of Ineffective Pain Management
The course of postsurgical pain can be prolonged.9 Lynch, et al, examined the extent and
evolution of pain after common major elective noncardiac surgical procedures.10 Patients
were interviewed on Postoperative Days 1, 2, and 3 to assess their pain on a scale of 0
(none) to 10 (worst imaginable). The mean pain score at rest was 2.6 on Postoperative
Day 1 and decreased to 2.3 on Postoperative Day 3. The mean pain score with movement
was 4.5 on Postoperative Day 1, which decreased to 4.2 on Postoperative Day 3. The
mean maximum pain score over the previous 24 hours was 6.3, which decreased to
5.6. Preoperative narcotic use and high baseline preoperative pain, defined as a score
≥4, were significantly associated with increased pain at rest, pain with movement, and
maximum pain. The authors concluded that these relatively high pain scores and minimum
reductions in pain from Postoperative Days 1 to 3 emphasize the need for more effective
pain management continuing into the postoperative period to facilitate mobilization and
recovery.
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Beauregard, et al, assessed the intensity, duration, and impact of pain after daysurgery procedures.11 In this study, 89 consecutive day-surgery patients completed
self-administered questionnaires before leaving the facility and at 24 hours, 48 hours,
and seven days after discharge. The results demonstrated that 40% of the patients
reported moderate to severe pain during the first 24 hours after discharge. While the pain
decreased over time, it was severe enough to interfere with daily activities in many of the
patients. Furthermore, the best predictor of severe pain at home was inadequate pain
control during the first few hours following the surgery.
In a study of 411 patients following hip fracture, Morrison, et al, reported that
postoperative pain is associated with increased hospital length of stay (LOS), delayed
ambulation, and long-term functional impairment.12 Although appropriate caution is
necessary when administering opioid analgesics to older adults, the data from this study
suggest that improved pain control may decrease LOS, enhance functional recovery, and
improve long-term functional outcomes.
Another consequence of ineffective pain management is the development of chronic
pain. A study conducted by Perkins and Kehlet suggested that the intensity of acute
postsurgical pain is a predictor of ongoing chronic postsurgical pain, which occurs in 15%
to 45% of patients after several commonly performed surgeries (eg, limb amputations,
breast surgery, gallbladder surgery, lung surgery, and inguinal hernia surgery).13
Moreover, once pain is established, it is difficult to control and can cause unnecessary
suffering.14
New Opportunities to Improve Economic Efficiency and Patient Outcomes
Related to Pain Management15
In addition to the clinical consequences of ineffective pain management, the economic
implications are also significant, particularly in regards to the additional costs associated
with prolonged lengths of stay in the postanesthesia care unit (PACU) and hospital as
well as patient readmissions. Patient satisfaction reports are also taking on greater
significance in the face of new federal regulations impacting how hospitals are
reimbursed moving forward and initiatives intended to improve the quality of patient care
(eg, the American College of Surgeons National Surgical Quality Improvement Program
[ACS NSQIP®], which focuses on reducing complications, improving outcomes, reducing
the length of hospital stay, and increasing satisfaction16).
Today, public reporting of patients’ perceptions of the care they receive creates new
incentives for hospitals to improve the quality of care they provide. The national standard
scoring system used by the Centers for Medicare and Medicaid Services (CMS) is
the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS)
survey.17 HCAHPS is the first national, standardized, publicly reported survey to measure
patients’ perspectives of their hospital experience and care. Most hospitals have
collected information regarding patient satisfaction for their own internal use; however,
until HCAHPS there were no common metrics and no national standards for collecting
and publicly reporting information about patients’ experiences of care. Since 2008,
HCAHPS has allowed valid comparisons to be made across hospitals on all levels, ie,
locally, regionally, and nationally.
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Discharged patients are asked to answer 32 questions about their recent hospital stay
that they are uniquely suited to address.18 The core of the survey consists of 17 questions
that ask “how often” or whether patients experienced a critical aspect of hospital care,
rather than if they were “satisfied” with the care. The survey encompasses eight key
topics: communication with doctors, communication with nurses, responsiveness of
hospital staff, pain management, communication about medicines, discharge information,
cleanliness of the hospital environment, and quietness of the hospital environment.19
A recent study found that the nurse work environment was significantly related to all
HCAHPS patient satisfaction measures; patients’ reports of satisfaction were higher
in hospitals where nurses practice in better work environments or with more favorable
patient-to-nurse ratios.20 As patient satisfaction becomes integrated into more pay for
performance programs and public reporting plans, hospitals will be further incentivized to
improve patient satisfaction.
In addition to public reporting, many hospitals are also using private patient surveys after
discharge to evaluate performance with the goal of process improvement. Hospitals are
also voluntarily becoming more transparent by making their ratings public on clinical
care, patient safety, and clinical experience. These rating systems are tied to the desire
for delivering quality care; they also have the capacity to influence patient choice in the
selection of health care practitioners. As a result of these developments, hospitals will
have to provide outstanding patient satisfaction to be financially sound.
A recent survey of medical-surgical nurses showed that 92% of hospitals had
implemented programs specifically to improve patient satisfaction; 84% said patient
satisfaction was very important to the financial health of the facility. Pain management
was noted to be a critical aspect of patient satisfaction; 98% of the respondents said that
pain relief was very important in predicting a patient’s satisfaction with his or her overall
experience at the hospital. In this regard, 78% of those surveyed said their hospital had
new guidelines and policies in place to improve postsurgical pain management; 28% of
the respondents also stated that inadequate postsurgical pain relief had a significant or
severe negative financial impact on their hospital.
Readmission of the surgical patient due to complications, including inadequate pain
relief and urinary retention, is an expense that soon will not be fully reimbursed by
Medicare, Medicaid, and other private payers.21 New health care reform legislations (ie,
the Affordable Care Act) indicate that as of 2012, Medicare and Medicaid programs may
reduce payments to hospitals for excessive unplanned patient readmissions within 30
days of discharge. A survey of nurse managers/directors showed that, on average, 14%
of colorectal surgery patients; 8% of obstetrics/gynecology patients; and 6% of plastic
surgery patients are readmitted for postsurgical pain problems. CMS recognizes that
premature discharge and poor transitions of care are indicators of poor quality and that
both of these situations are costly: the costs of a hospital admission are approximately
$10,000; therefore, reducing readmissions by 20% would reduce Medicare spending by
$500 million.22
9
Pain was found to be the single most common reason for re-admissions after same-day
surgery, and the mean cost of follow-up care was $13,900 per re-admitted patient.23
These readmissions will soon be a major financial burden on hospitals. Poorly controlled
postsurgical pain may also predispose patients to chronic pain and long-term disability,
each of which represents a potential expense for the payer. Another financial factor
that hospitals should take into consideration is the cost of litigating lawsuits filed over
complications arising from pain management. Finally, as noted, pain management is an
important element of patient satisfaction; inadequate pain relief will be reflected in patient
satisfaction scores.
Surgeons are also looking for high-quality support from the anesthesia, operating room,
PACU, and medical-surgical staff. Hospitals need to have consistently high-performing
specialists in these areas to attract the best surgeons; hospitals should also offer up-todate and advanced technologies in order to recruit and retain the best physicians. Among
these factors are the hospital’s formulary and its expertise in using new medications. The
field of postsurgical pain management is evolving, as evidenced by the new medications
coming to market, including new protocols for intraoperative administration of pain
medications. Hospitals, surgeons, and pain management teams that stay at the forefront
of postsurgical pain management will be better positioned to attract the top physicians
and gain patient referrals, resulting in better financial performance.
Today, there is also an increasing interest in evidence-based practice as a way to
reduce costs and also improve care. While there is considerable variability in how a
given medical condition is treated at the individual patient level (due to the unique
aspects of a patient’s case; clinician preferences; and differences among hospital
equipment, formularies, and established processes), this variability is seen as a potential
source of inefficiency by the government and other payers. Therefore, these entities
are driving efforts to establish standard treatment protocols, or clinical pathways, that
optimize outcomes, reduce complications, and reduce costs for treating a condition
across a large patient population. This approach is likely to become more accepted
by hospitals as reimbursement shifts toward the DRG model and away from fee-forservice. Treatment protocols must be examined for safety, efficacy, and the cost of
care under these protocols; therefore, providers need to adopt protocols that optimize
patient outcome while also containing costs. The evolution of evidence-based medicine
has identified pain management as one area in which economic efficiencies could be
improved. The institution of early multimodal pain management protocols may provide
not only significant clinical advantages but economic benefits as well. In the survey of
medical-surgical nurse managers and directors, 46% said that at least 20% of cases
had excessive costs for postsurgical pain management; 60% reported that at least
20% of cases had excessive costs for managing complications due to postsurgical pain
management. These high direct and indirect costs associated with the management
of postsurgical pain could be reduced by adoption of appropriate protocols and
therapeutics. There is emerging evidence that standard regimens specifically geared
toward the management of postsurgical pain can reduce overall direct medical costs.24
10
It is clear that hospitals constantly face pressures to contain costs, while improving
the quality of patient care they deliver. The old paradigm of “more care” is now being
replaced with “better care” in an effort to improve economic efficiencies and also slow
the inflation of health care costs. Today, replacing the historical fee-for-service payment
structure with a prospective payment system based on bundling a patient’s treatment,
such as according to a diagnosis-related group (DRG) is one of the key factors driving
improvements in overall efficiencies. This type of payment structure is designed to
encourage facilities and health care providers to find the most economically efficient
treatment for a patient and reduce unnecessary services. As a result, hospitals are
carefully examining the effectiveness of treatments by evaluating both their costs and
outcomes. Within a bundled-services model of reimbursement, there are various ways
to improve economic efficiency while simultaneously improving patient outcomes. One
way is to eliminate waste, eg, unneeded care and an unnecessarily prolonged length of
hospital stay. Another way is to minimize avoidable side effects and complications such
as hospital-acquired infections, pressure ulcers, and embolism due to lack of movement,
as well as high-profile avoidable problems, such as medical errors and “never” events,
including wrong-site surgery, incorrect drug administration, or falls. CMS and many
private insurers will no longer reimburse hospitals for the additional costs of care
resulting from these complications and events, thereby shifting the cost of these mistakes
to the hospital and thus reinforcing their prevention. A third way to improve efficiencies
is innovation, ie, the development of new treatments that are more effective, have a
greater positive impact on patient outcomes, and are ultimately less expensive than
current standards of care. In this regard, payers are closely evaluating new drugs and
devices not only in terms of their safety and efficacy, but also for the potential to reduce
overall costs of care. This type of economic evaluation will be the crucial means by which
hospitals will measure economic efficiency in the future.
Economic Considerations of Opioid Therapy25
Along with the clinical considerations, other economic and operational aspects of pain
management should also be high priorities for care providers. Hospitals consume
substantial resources in direct care, equipment, supplies, and pharmaceuticals in
managing pain. Because opioids are often the mainstay of pain management and are
generally inexpensive, providers may not consider treatment of pain as a priority in
cost reduction efforts; but these treatments have inherent risks that can lead to patient
complications that further increase the cost of care. Relatively small amounts of opioids
can increase the risk of opioid-related adverse events (ORAEs), length of stay, and
associated costs, as documented:
• One study found that ORAEs following surgery increased the median
hospitalization costs by 7.4% and the median length of stay by 10.3%.26
• A retrospective study of patients undergoing elective colorectal surgery found that
intravenous opioid therapy was significantly associated with postoperative ileus
and prolonged length of stay, particularly when the maximum hydromorphone
dose per day exceeded 2 mg.27
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The risk of ORAEs increases in patient populations where opioid use is often
problematic, such as sleep apneic and obese patients, the elderly and opioid-tolerant
patients (eg, patients with rheumatoid arthritis, osteoarthritis, or back pain). Increasingly,
providers are looking for new methods to manage pain that are more effective and
minimize costly ORAE complications; therefore, alternative, non-opioid-based pain
management options should be considered. A variety of non-opioid pain therapies, such
as non-steroidal anti-inflammatory drugs (NSAIDs) and local analgesics, are also used to
treat postsurgical pain, but these therapeutics also bear risks, as do the infusion methods
often used for administration of opioids and non-opioids alike (see Table 1). Increasingly,
providers are looking for new methods of managing pain that are more effective and that
also minimize costly complications.
Table 1 – Clinical Risks in Postsurgical Pain Management Associated with NonOpioid and Continuous Infusion Therapies
Therapy
Clinical Risks
Non-Opioids
Inadequate pain relief
Renal toxicity
Gastrointestinal ulceration
Bleeding
Cardiotoxicity
Continuous Infusion (Local or
Systemic)
Catheter displacement
Infection
Poor control of dosage
Delayed ambulation
Costs of Patient-Controlled Analgesia28
Routine therapy for pain involves several expenses in addition to the medications
themselves. Some modalities, such as patient-controlled analgesia (PCA) and
elastomeric pain pumps entail the cost of equipment and supplies as well as pharmacy
expenses to fill the order. Table 2 outlines the average costs of PCA and elastomer
pain pumps. The average cost per patient stay for intravenous (IV) opioids by PCA is
$616: $235 for the PCA pump, $179 for tubing and fittings, and $202 to fill the opioid
order in the pharmacy. Additionally, opioids incur extra expenses for the hospital in
terms of secure storage and tracking within the hospital. The average cost per patient
stay for local anesthetic for continuous nerve blocks is $646: $284 for the elastomeric
pump, $166 for the tubing and fittings, and $196 to fill the order in the pharmacy.
These substantial expenses are direct costs, but there are many indirect costs as well.
Monitoring patients, particularly those on opioids, nerve blocks, and analgesic wound
infiltration, requires the use of monitoring equipment and nursing time for periodic
evaluation of vital signs. The average time needed for nurses to initiate, maintain,
document, and monitor PCA was 3.9 hours and 3.4 hours for nerve block. Hospitals
might consider whether the time required for these tasks could be devoted to other tasks
that accelerate recovery and increase patient throughput. Table 2 outlines the average
costs associated with these modalities.
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Table 2 – Average Costs per Patient Stay Associated with Supplies and Services
for PCA and Elastomeric Pumps
Modality
PCA
Elastomer Pump
Delivery Pump
$ 235
$ 284
Fittings and Tubing
$ 179
$ 166
Pharmacy
$ 202
$ 196
3.9 hours
3.4 hours
Staff Time to Maintain,
Document, and Monitor
Beyond the resources needed for postsurgical pain management, there are significant
and potentially much higher expenses arising from potential complications; one of the
most costly of these is prolonged length of stay, which is a common result of opioid side
effects such as nausea, ileus, and urinary retention (see Table 3).
Table 3 – Additional Length of Hospital Stay (Days) due to Side Effects from Pain
Management (U.S.), 2011 (N=50)
Average Mean Number of
Additional Days
Side Effect
Respiratory Depression
3.3
Nausea and/or Vomiting
2.5
Ileus and/or Constipation
3.4
Urinary Retention
2.8
Somnolence
2.0
Delirium
3.1
Pruritus
1.8
Delayed Ambulation
3.0
In the past, hospitals could bill for the additional costs of care associated with increased
lengths of stay; however, in today’s reimbursement system of bundled payment, these
additional costs are a major economic concern for hospitals. An additional length of
stay of one day costs a hospital $2,095 on average for a general/colorectal surgery
patient; $1,990 for an obstetrics/gynecology patient, and $1,868 for a plastic surgery
patient. Hospitals are now incentivized to discharge patients sooner. Other side effects
may require additional costs of medication and care, such as antihistamine for pruritus
($100 per patient stay and 1.6 hours of nurse time). While rare, respiratory depression
13
due to opioid incurs high costs in terms of extra monitoring and treatment ($200 and 3.8
hours of nursing time). In addition, treating the delirium that results from postsurgical pain
management costs $152 on average, and 3.4 hours of nurse time.
Clearly there are many direct and indirect costs associated with postsurgical pain
management. Hospitals will need to establish priorities and protocols that allow them to
continue to improve postsurgical pain management while reducing overall and avoidable
costs.
OPIOID THERAPY: PROBLEMS AND LIMITATIONS29
Historically, monotherapy with opioids has been the mainstay of postsurgical pain
management regimens and they remain a foundation of many current treatment modalities.
While opioids are often effective, they have several idiosyncratic or dose-limiting side
effects that limit their practical efficacy and also subject patients to adverse drug events.
The most serious adverse events include respiratory depression and sedation, which
increase the risk for aspiration, respiratory failure, impaired mobility, and falls. Moreover,
more common reactions, eg, nausea, vomiting, constipation, and ileus, may occur even
with low dosages of opioids, which can result in significant discomfort and increased
lengths of stay. For these reasons, increasing the dose of opioids alone is neither an
adequate nor appropriate strategy for effective pain management in postsurgical patients.
The consequences of unrelieved postoperative pain and opioid-related adverse events are
outlined in Table 4.
Table 4 – Consequences of Unrelieved Postoperative Pain and Opioid-Related
Adverse Events30,31
System/Parameter
Cardiovascular System
Coagulation
Adverse Effects
Decreased arterial blood pressure, increased heart
rate, infarction, myocardial ischemia
Increased platelet aggregation, thromboembolism,
venous stasis
Gastrointestinal System
Decreased intestinal motility, ileus, increased
secretions, nausea, vomiting
Immunologic System
Increased risk for infection, impaired immune function
Musculoskeletal System
Neurologic System
Fatigue, muscle atrophy and weakness, limitations in
movement
Increased risk for developing chronic pain syndromes
Psychological
Anger, anxiety, depression, fear
Pulmonary System
Atelectasis, diaphragmatic dysfunction,
hypoventilation, hypoxemia, impaired ventilation and
coughing, reduced vital capacity, respiratory and
abdominal muscle spasm (splinting)
Increased urinary sphincter tone, urinary retention
Renal System
Overall Recovery
Delayed recovery and discharge, increased expenses,
increased use of health care resources
14
Joint Commission Sentinel Event Alert: Safe Use of Opioids in Hospitals32
On August 8, 2012, The Joint Commission issued a sentinel alert on the safe use of
opioids in hospitals. This report indicated that, of the opioid-related adverse drug events,
including deaths that occurred in hospitals and were reported to The Joint Commission’s
Sentinel Event database (from 2004-2011):
• 47% were wrong dose medication errors;
• 29% were related to improper monitoring of the patient; and
• 11% were related to other factors, including excessive dosing, medication
interactions, and adverse drug reactions.
These reports emphasize the need for the judicious and safe prescribing and
administration of opioids, as well as the need for appropriate monitoring of patients.
When opioids are administered, the potential for opioid-induced respiratory depression
should always be considered because:
•
•
•
•
The risk may be greater with higher opioid doses;
The occurrence may actually be higher than reported;
There is a higher incidence observed in clinical trials;
Various patients are at higher risk including postoperative patients, particularly
those undergoing upper abdominal or thoracic surgical procedures;
• Patients with sleep apnea; and
• Patients who are morbidly obese, who are very young, who are elderly, who are
very ill, and who concurrently receive other drugs that are central nervous system
(CNS) and respiratory depressants (eg, anxiolytics, sedatives).
Therefore, the safe use of opioids in hospital settings relies on an accurate pain
assessment and the application of appropriate pain management techniques. In addition,
one activity to help avoid accidental opioid overuse is an individualized, multimodal
treatment plan to manage pain. A multimodal approach combines strategies such
as psychosocial support, coordination of care, the promotion of healthful behaviors,
nonpharmacologic approaches, and non-opioid pain medications. Upon assessment, the
best approach may be to start with a non-narcotic. The Joint Commission recognizes that
not all pain can be eliminated; therefore, their standards provide for goal-related therapy.
The Joint Commission Pain Management Standards33
The Joint Commission Pain Management Standards have been in effect since January 1,
2001 for accredited hospitals, critical access hospitals, ambulatory care facilities, officebased surgery practices, and other practice settings; they have increased awareness of
the importance of safe and effective pain management. These standards address the
assessment and management of pain, specifically requiring organizations to:
• Recognize the right of patients to appropriate assessment and management of
pain;
• Screen patients for pain during their initial assessment and, when clinically
required, during ongoing, periodic re-assessments; and
• Educate patients suffering from pain and their families about pain management.
15
The pain management standards require that patients be asked about pain, depending
on the service the organization is providing. While there are some services that do not
require a pain assessment (eg, if a patient is having an x-ray); however, if a patient
is experiencing pain, appropriate care should be made available. The organization’s
response to a patient’s pain is based on the services it provides. If screening indicates
that pain exists, the organization may assess and treat the pain; assess the pain and
refer the patient for treatment; or refer the patient for further assessment. Patients are
also encouraged to report pain and cooperate with the prescribed treatment regimen.
It is important to note that the lack of adequate postoperative pain treatment may lead
to persistent pain after surgery, which is often overlooked; overall, inadequate pain
management increases the use of health care resources and health care costs.34 As
noted above, the experience of pain influences a patient’s satisfaction with both their
surgical and overall hospitalization experience. These are key factors in the face of
today’s federal regulations and initiatives that focus on improving the quality of care and
impact the facilities reimbursement.
PATHOPHYSIOLOGY OF SURGICAL PAIN
In order to understand the role of local anesthetics in effective management of
postsurgical pain, the perioperative nurse should have a working knowledge of analgesia
and the inflammatory responses to surgery; this includes knowledge of the various types
and manifestations of pain and the requirements for pain production.35
Types of Pain36
There are three commonly reported types of pain: visceral, neuropathic, and nociceptive
or somatic. Visceral pain is produced by activation of nociceptors in any of the visceral
tissues. This type of pain is often referred to as distant pain, as it is poorly localized.
An example of visceral pain is the right upper quadrant abdominal and shoulder
pain associated with cholecystitis. Neuropathic pain is typically intermittent and often
experienced as an area of sensory loss or numbness. An example of neuropathic pain
is carpal tunnel syndrome. Nociceptive or somatic pain is well localized, described as
familiar in quality, and often associated with inflammation. Somatic pain is produced by
activation of nociceptors in the somatic tissues (eg, muscles, skeleton, and skin); surgical
pain is an example of somatic pain.
Requirements for Pain Production37,38
All three types of pain have one thing in common: the four basic requirements for the
production of pain, as outlined below.
• Transduction.Transduction is the process by which afferent nerve endings
participate in translating a painful stimulus into nociceptive impulses. Transduction
occurs when mediators, eg, substance P, serotonin, histamine, and bradykinin
are released at the tissue injury site. These mediators then stimulate peripheral
sensory afferent nerves that extend to the dorsal horn of the spinal cord. A painful
or noxious stimulus is first carried by the faster A-delta fibers, and then by the
slower C fibers; silent nociceptors, afferent nerves that do not respond to external
16
stimulation unless inflammatory mediators are present, are also involved in
transduction.
• Transmission. Transmission is the process by which impulses are sent to the
dorsal horn of the spinal cord, and then along the sensory tracts to the brain.
Transmission occurs when ascending nerves extending from the dorsal horn of
the spinal cord to the brain are stimulated by the peripheral sensory afferents.
• Modulation. Modulation is the process of dampening or amplifying these
pain-related neural signals. Modulation occurs when descending pathways
to the dorsal horn modulate the activity of the peripheral nerves by releasing
enkephalins and endorphins.
• Perception. Perception of pain occurs at the level of the brain; it refers to the
subjective experience of pain resulting from the interaction of transduction,
transmission, modulation, and also the psychological aspects of the individual.
Pain and the Inflammatory Response: The “Wind-Up” Phenomenon39,40
In surgical wounds, tissue damage stimulates an inflammatory response. After the
incision is made, a cascade of hyperexcitable events occurs in the nervous system. This
physiologic “wind-up” phenomenon begins at the skin, is potentiated along the peripheral
nerves, and ends in a hypersensitivity response from the dorsal horn of the spinal cord
and the brain. Inflammatory cells that surround the areas of tissue damage produce
cytokines and chemokines, substances that are meant to mediate the process of healing
and tissue regeneration. However, these substances are also irritants and change the
properties of the primary sensory neurons surrounding the area of trauma. Therefore,
the primary features that trigger inflammatory pain include damage to the high-threshold
nociceptors (ie, peripheral sensitization), modifications and modulation of the neurons in
the nervous system, and amplification of the excitability of neurons within the CNS. This
represents central sensitization and is responsible for hypersensitivity, in which areas
adjacent to the area of the actual injury hurt as if they are injured. These tissues also
can respond to stimuli that ordinarily do not produce pain, such as a touch, clothing, light
pressure, or a hairbrush, as if they are painful.
The “wind-up” phenomenon causes untreated pain to get worse, since the nerve fibers
transmitting the painful impulses to the brain essentially become “trained” to deliver pain
signals better and with an intensity that is over and above what is needed to get the
affected person’s attention. To further complicate this situation, the brain also becomes
more sensitive to the pain and as a result, the pain feels much worse even though the
injury is not worsening.
Preemptive Analgesia41,42
The concept of preemptive analgesia was first formulated about 100 years ago. It is an
antinociceptive treatment which proposes that the perception of pain can be reduced with
the use of analgesics capable of inhibiting CNS sensitization before the painful stimulus
occurs, ie, counteracting the “wind-up” phenomenon. Preemptive analgesia is initiated
before the surgical procedure in order to reduce the peripheral and central sensitization
that occurs from tissue damage after surgery. Because of this “protective” effect on the
17
nociceptive system, preemptive analgesia has the potential to be more effective than
similar analgesic treatment initiated after surgery.
Pain Assessment43,44
Because effective pain management is one of the highest priorities in the PACU,
assessment of pain and pain control in all postsurgical patients is critical. Patients should
be assessed for pain on admission to the PACU and at frequent intervals. It is important
to remember that pain is a subjective experience, ie, it is whatever the patient says it
is and that, despite similar surgical procedures, not all patients respond to pain in the
same manner. Because patients may not verbalize their pain, perioperative nurses often
require objective signs of discomfort as well as subjective reports of pain from the patient.
Pain and pain control should be assessed using a validated pain scale (eg, Numeric
Pain Intensity Scale, Visual Analogue Scale, the Wong-Baker FACES Pain Rating
Scale); these assessments should be correlated with the patient’s self-report as the most
important measure of pain intensity. In patients who cannot self-report, other assessment
measures include behavioral signs, eg, restlessness or crying as well as physiologic
indicators such as elevated vital signs.
MULTIMODAL ANALGESIA
Overview45
The use of multimodal analgesia involves the administration of two or more analgesic
agents that act through different mechanisms with the goal of improving postsurgical pain
management, decreasing the use of opioids, and consequently reducing their associated
adverse drug events in postsurgical patients. Even though pain results from complex
physiologic mechanisms that involve multiple receptors in both the central and peripheral
nervous systems, as outlined above, single or monotherapy with opioids has been a
foundation of postsurgical pain management. However, no single analgesic targets
all types of pain receptors or signaling pathways; furthermore, the amount of opioids
that can be administered is limited due the risk for adverse drug events that lead to
patient discomfort, delayed recovery, prolonged LOS, and increase costs, as previously
discussed.
Non-opioid alternatives, eg, NSAIDs, acetaminophen, and local anesthetics are
recognized as effective components of a multimodal pain regimen postoperatively. A
multimodal approach can reduce opioid use and opioid-related adverse drug events and
also result in earlier patient ambulation as well as discharge.
Professional Guidelines for Multimodal Postsurgical Pain Management
Two key organizations recommend a multimodal approach for effective postsurgical pain
management.
• Veterans Administration/Department of Defense (VA/DoD) Clinical Practice
Guideline for the Management of Postoperative Pain.46 A summary of the key
points of this guideline state that:
o Postoperative pain management should be multimodal and individualized
for the particular patient, operation, and circumstances. Understanding of
18
o
o
o
o
both the range of available interventions and considering the type of surgical
procedure are essential to safe and effective pain management.
Selection of a pain management option should be determined by balancing
the advantages, disadvantages, contraindications, as well as patient
preference. For most patients, more than one modality will be needed for
successful pain management.
Interventions for postoperative pain management include both pharmacologic
(ie, using the primary classes of medication: opioids, NSAIDs, and local
anesthetics) and non-pharmacologic (ie, cognitive and physical modalities).
Evaluation of the balance between pain control and side effects should be
routine, timely, and specific. If indicated, the management plan should be
modified.
Incisional local anesthetic infiltration is included for specific surgical
procedures, eg, thoracic (non-cardiac), upper abdominal. This guideline
notes that infiltration of the incision/wound with local anesthesia improved
postoperative analgesia provided by epidural bupivacaine/morphine during
mobilization and also reduced the need for supplemental intramuscular
morphine.
• American Society of Anesthesiologists (ASA) Guidelines Practice Guidelines for
Acute Pain Management in the Perioperative Setting.47 These guidelines also
state that whenever possible, multimodal pain management therapy should
be used. Dosing regimens should be administered to optimize efficacy while
minimizing the risk of adverse events. The selection of medication, dose, route,
and duration of therapy should be individualized.
Multimodal Pain Management Profiles
Based on the understanding of the peripheral and central mechanisms involved in
pain, it is beneficial to use a multimodal approach with combinations of analgesics from
various classes as well as different sites of analgesic administration to achieve effective
postsurgical pain management.48 An example of a multimodal pain management order
set, with a brief review of each drug classification, is outlined below.
• Preoperative:
1. Celebrex® (celecoxib) 400 mg PO, continue 200 mg PO BID for 3 weeks
following surgery. (Cox-2 Inhibitor). COX-2 inhibitors are a subclass of
NSAIDs.49 NSAIDs work by reducing the production of prostaglandins, which
are chemicals that promote inflammation, pain, and fever. The enzymes
that produce prostaglandins are called cyclooxygenase (COX). There are
two types of COX enzymes, COX-1 and COX-2; both of these enzymes
produce prostaglandins that promote inflammation, pain, and fever. NSAIDs
block the COX enzymes and reduce production of prostaglandins; therefore,
inflammation, pain, and fever are reduced by all COX inhibitors.
2. Versed (midazolam) 1-2 mg IV once pre-op (Benzodiazepine).
Benzodiazepines are a class of agents that work on the CNS, acting
selectively on gamma-aminobutyric acid-A (GABA-A) receptors in the
19
brain.50 These agents enhance response to the inhibitory neurotransmitter
GABA, by opening GABA-activated chloride channels and allowing chloride
ions to enter the neuron, making the neuron negatively charged and
therefore, resistant to excitation.
3. Oxycodone SR 10/20 mg orally (Opiate). Opiates are narcotic analgesics
that directly depress the CNS.51 Opioids attach to specific proteins, ie, opioid
receptors, which are found in the brain, spinal cord, and gastrointestinal
tract and block the transmission of pain signals to the brain. Opioids also
tend to cause drowsiness, bradycardia, vasodilatation, and depression of
coughing and breathing reflexes.
• Intraoperative:
1. Lidocaine 1% or 2% infiltrated pre-incision at intended surgical site (Local
Anesthetic for pre-emptive anesthesia, as described above).
2. Fentanyl IV (Opiate, as described above).
3.EXPAREL® (liposomal bupivacaine injectable suspension) 1.3% 20cc / 266
mg (lipsomal bupivacaine injectable suspension for postoperative
analgesia, as described below).
4.Tylenol® (acetaminophen) 1000 mg IV q 6 hours x 24 hours then PO
(Start at end of surgery in OR) (Non-narcotic analgesic/antipyretic).
Non-narcotic analgesics have principally analgesic, antipyretic, and antiinflammatory actions; they act primarily in peripheral tissues to inhibit the
formation of prostaglandins; they do not bind to opioid receptors.52
• Postoperative:
1. Ketorolac 30 mg IV q 6 hours x 24 hours then prn (NSAID). As noted
above, NSAIDs work on a chemical level by blocking the COX-1 and COX-2
enzymes to reduce the production of prostaglandins, thereby reducing
inflammation and pain.53
2. Dilaudid IV PRN for severe breakthrough pain 0.5-2 mg IV q 3 hours PRN
(Opiate, as described above).
3. Oxycodone 5-15 mg q 3 hours PRN moderate pain (Opiate, as described
above).
4. Methylprednisolone acetate 40 mg IV (Corticosteroid). Corticosteroids
reduce pain by also inhibiting prostaglandin synthesis, which leads to
inflammation, and reducing vascular permeability that results in tissue
edema.54
5. Neurotonin® (gabapentin) 300 mg q hs for 3 weeks after surgery (Anticonvulsant for neuropathic pain). While the mechanism of action of
agents such as gabapentin is not fully understood, it is thought to work by
binding to the calcium channels in nerve cells in the brain and spinal cord,
which affects the release of various neurotransmitters from these nerve
cells.55 Gabapentin is believed to reduce the release of the neurotransmitter
20
glutamate, which acts as a natural ‘nerve-exciting’ agent. Glutamate is
released when electrical signals build up in nerve cells and subsequently
excites more nerve cells. Reducing the release of glutamate from the nerve
cells in the brain is thought to help stabilize the electrical activity in the brain.
6. Enteric coated aspirin 325 mg bid for deep vein thrombosis (DVT) prophylaxis
(Salicylates). Salicylates are also NSAIDs and inhibit the synthesis of
prostaglandin and other mediators in the process of inflammation; they have antiinflammatory, antipyretic, and analgesic properties.56
7. Tylenol 1000 mg IV q 6 hours x 24 hours then PO (Non-narcotic analgesic/
antipyretic, as described above).
8. Intermittent cryotherapy (Application of cold source). Reduces edema at the
site of inflammation as a result of vasoconstriction.
PHARMACODYNAMICS OF LOCAL ANESTHETICS57,58
In order to understand the impact of infiltration of the surgical wound with local
anesthetics on postsurgical pain control, it is helpful to review their definition and
mechanisms of action. Local anesthetics are defined as pharmacologic agents capable
of producing a loss of sensation in an area of the body; when they are used on specific
nerve pathways, analgesia can be achieved.
Nerves conduct impulses that provide information to the CNS regarding the type,
degree, and magnitude of pain. Cytoplasm inside the nerve cell (including the axon)
contains positively charged potassium ions and negatively charged proteins. The
potassium ions can freely move in and out of the cytoplasm, whereas the proteins are
not freely diffusible. The fluid outside the nerve cell and axon contains positively charged
sodium ions and negatively charged chloride ions; these ions are freely diffusible in the
cytoplasm. However, sodium is quickly pushed out of the nerve cell via a sodium pump.
Outside the cell, the concentration of the positively charged potassium is low. Inside the
cell, the concentration of potassium is high and the concentration of negatively charged
chloride ions is low. The freely diffusible potassium ions are held inside the nerve cell
by an excess of negatively charged ions. When a nerve impulse is conducted down
the nerve fiber, the nerve membranes become permeable (due to depolarization) to
the positively charged sodium ions. These sodium ions are conducted through sodium
channels, or pores, in which a “gate” controls their passage to the inside of the nerve
cell. Once the sodium has reached a certain ionic concentration, the gate closes in the
sodium channels. The membrane permeability to potassium increases, which allows
potassium back into the cytoplasm; sodium is pumped out of the nerve cell.
Because local anesthetics are quite lipid soluble, they can diffuse through the cell
membrane. Therefore, most local anesthetic agents exert their analgesic effects by
inhibiting depolarization of the nerve membrane and also by interfering with sodium and
potassium currents. While most nerve fibers are sensitive to local anesthetics, nerves
with small diameters tend to be more sensitive than those larger in diameter. There are
three types of nerve fibers (types A, B, and C): type A fibers are the largest in diameter
and type C are the smallest. Type A fibers transmit pressure sensation and motor
21
commands; type C fibers transmit pain and temperature sensation. Therefore, patients
who have blocked type C fibers experience analgesia and reduced pain sensation
but can still feel pressure and the ability to move because the type A fibers are fully
functioning. In addition to analgesic effects, most local anesthetics also have vasodilatory
effects, which increase the risk of local bleeding and the rate of systemic drug absorption;
these effects may also decrease the duration of analgesia. This is why epinephrine, a
potent vasoconstrictor, is often combined with local anesthetic agents to prolong the
duration of action and reduce bleeding at the site.
Local anesthetic agents can be divided into three groups, according to potency:
• Low potency – procaine and chloroprocaine.
• Intermediate potency (ie, twice the potency of procaine) – lidocaine, cocaine,
mepivacaine, and prilocaine.
• High potency (ie, approximately six to eight times more active than procaine) –
tetracaine, bupivacaine (and its isomers ropivacaine and chirocaine).
Local anesthetics are also grouped pharmacologically into two categories:
• Amides (eg, lidocaine, mepivacaine, prilocaine, etidocaine, and bupivacaine) –
these agents are metabolized in the liver, have no real history of documented
allergic reactions, have good penetrance, and are stable.
• Esters – except for cocaine, esters are hydrolyzed primarily in the plasma and
are metabolized more rapidly than amides. Because esters are metabolized to
paraaminobenzoic acid (PABA), they are associated with an increased incidence
rate of allergic reactions. In general, esters have poor penetrance and fair to poor
stability.
Local anesthetics are also categorized according to their duration of action:
• Short-duration: procaine, chloroprocaine.
• Intermediate-duration: cocaine, lidocaine, mepivacaine, prilocaine.
• Long-duration: bupivacaine, etidocaine, levobupivacaine, ropivacaine, tetracaine.
Complications associated with the use of local anesthetics include:
• Allergic reactions. Allergic reactions can be divided into four types: contact
dermatitis; serum sickness, including fever, lymphadenopathy, and urticarial
2 to 12 days after injection; anaphylactic reaction, characterized by dyspnea,
cyanosis, and death; and atopic response, including bronchospasm, urticaria, and
angioneurotic edema.
• Toxicity. Local anesthetic toxicity can occur as a result of inappropiate dosing,
inadvertent intravascular injection of the agent, variation in the patient’s response,
or injection of the agent into a highly vascular area. Local anesthetic toxicity can
cause adverse effects on skeletal muscle, cardiac tissue, and the neurologic
system. Symptoms associated with local anesthetic toxicity are muscular
twitching, cardiac electrophysiologic events (ie, Qtc prolongation, heart block,
and possible cardiac collapse), hypotension, and/or seizures.
22
Infiltration of Local Anesthetics at the Surgical Site: The Importance of
Technique
Intraoperative management of pain is critical to the patient’s overall perception of
pain.59 Local anesthetics are often used intraoperatively to reduce the transduction
of nociceptive signals that are produced at the surgical incision site, or in minimally
invasive procedure, at the trocar insertion sites. The use of local anesthetics as part of
a multimodal approach to pain management can contribute to a considerable reduction
in opioid dosage with minimal side effects.60 Most local anesthetics can be used for
infiltration of the surgical wound as part of a multimodal approach; however, agents with
a longer duration of action are preferred.61
Infiltration of local anesthetics into the surgical wound is one administration route that
allows for minimally invasive exposure, results in immediate pain relief, and may improve
patient satisfaction.62 With infiltration, the local anesthetic agent can be injected directly
into the area of tissue or a surgical site, where it blocks the activity of the nerve endings
that transmit pain signals directly from the surgical site. Infiltration is generally performed
by the surgeon, either at the beginning or end of a surgical procedure. Although
infiltration techniques vary by surgeon, in order to achieve optimal analgesic effect,
the infiltrated drugs should reach both superficial and deep tissues at the surgical site,
including the subcutaneous tissue, the fascia, and the muscle layer.
It should be noted that proper infiltration technique is a key factor in ensuring optimal
efficacy, as well as safe administration, of any local anesthetic agent.63 The potential
for inadvertent intravascular injection is of particular concern. When injected into the
bloodstream, local anesthetics can produce systemic reactions involving the CNS and
cardiovascular systems. Techniques to avoid inadvertent intravascular injection include
moving the needle during infiltration, plunger withdrawal, and syringe withdrawal.
Moving the needle during infiltration also permits even distribution of the local anesthetic
throughout the tissue and causes less tissue distention, since no single area is
excessively infiltrated.
NOVEL LOCAL ANESTHETIC AND DELIVERY PLATFORM FOR
LOCAL INFILTRATION OF THE SURGICAL WOUND
Because the pain management paradigm has shifted to an increased use of multimodal
analgesia, the role of local anesthetics has come to the forefront.64 Recent advances in
several therapeutic approaches have substantially improved postsurgical pain control
over the past several years, including the development of new local analgesic agents and
novel delivery platforms with an extended duration of action, thereby broadening their
potential in acute postsurgical pain management.
Liposomal Bupivacaine
Today, a long-acting local anesthetic that may provide effective postsurgical pain control
and reduce the need for opioids can be a valuable component of a multimodal pain
management regimen.65 As noted above, long-duration local anesthetic agents are
preferred for wound infiltration; bupivacaine provides a rapid onset of action and is one of
23
the longest-acting local anesthetics because of its high lipid soluble and protein-binding
properties.66 However, the use of bupivacaine for postoperative pain control is limited
by its short duration of analgesic efficacy (in general, about six to eight hours), which is
inadequate to effectively manage postsurgical pain, which lasts for 24 to 48 hours.67
The development of a novel long-acting liposomal bupivacaine injectable suspension
may provide analgesia and reduce the need for opioids in the acute postoperative period;
it was approved by the U.S. Food and Drug Administration (FDA) in October 2011.68
This product combines bupivacaine and a novel drug delivery system that is composed
of mutivesicular liposomes that consist of microscopic, spherical, lipid-based particles
composed of a honeycomb of numerous nonconcentric, internal aqueous chambers
that contain the encapsulated drug. The nonconcentric characteristic of the liposomes
allows for progressive breakdown and reorganization of the lipid bilayer; thus, this
preparation extends the duration of the local anesthetic action by slow release from the
liposome over an extended time period, which delays the peak plasma concentration in
comparison to plain bupivacaine administration.69,70
Indications and Injection Techniques71
Liposomal bupivacaine is indicated for single-dose infiltration into the surgical site to
produce postsurgical analgesia. It should be injected slowly into soft tissues of the
surgical site (see Figure 1), using a 25 gauge or larger bore needle, with frequent
aspiration to check for blood and minimize the risk of intravascular injection. The
maximum dosage should not exceed 266 mg (20 mL, 1.3% of undiluted drug). It can be
administered undiluted or diluted to up to 0.89 mg/mL (ie, 1:14 dilution by volume) with
normal (0.9%) sterile saline for injection or lactated Ringer’s solution. The vials should be
inverted to re-suspend the particles immediately prior to withdrawal from the vial; multiple
inversions may be necessary to re-suspend the particles if the contents of the vial have
settled. The medication should be used within four hours of opening.
Figure 1 – Infiltration of Liposomal Bupivacaine
24
Contraindications and Safety Considerations72
Liposomal bupivacaine is contraindicated in obstetrical paracervical block anesthesia.
The patient’s cardiovascular and neurological status, as well as vital signs should
be monitored during and after injection of liposomal bupivacaine, as with other local
anesthetics. Because bupivacaine is metabolized by the liver, this agent should be
used cautiously in patients with hepatic disease. Patients with severe hepatic disease,
because of their inability to metabolize local anesthetics normally, are at a greater risk of
developing toxic plasma concentrations. Other formulations of bupivacaine should not be
administered within 96 hours after administration of liposomal bupivacaine. This agent
should not be admixed with lidocaine or other non-bupivacaine-based local anesthetics;
it may be administered after at least 20 or more minutes following local administration of
lidocaine. Adverse reactions following administration of liposomal bupivacaine include
nausea, constipation, and vomiting. Its safety and effectiveness in pediatric patients
under the age of 18 have not been established.
Literature Review
Studies have demonstrated liposomal bupivacaine to be an effective tool for postsurgical
pain relief with the possibility to reduce the need for opioids; it has also been found
to have an acceptable adverse effect profile.73 Several key studies demonstrating the
clinical and economic benefits of this agent are discussed below and summarized in
Table 5.
• Cohen conducted a study of 39 patients undergoing open colectomy to assess
the opioid burden and health economic outcomes in adult patients who received a
liposomal bupivacaine-based multimodal analgesic regimen in comparison with a
standard opioid-based regimen for postsurgical pain.74 The results demonstrated
that the:
o Mean total amount of postsurgical opioids consumed was significantly less in
the multimodal analgesia group compared with the opioid analgesia group;
o Average total cost of hospitalization in the multimodal group was $8,766
versus $11,850 in the opioid group; and
o Median length of hospital stay was 2.0 days versus 4.9 days, respectively.
• Dasta, et al, assessed the comparative efficacy of liposomal bupivacaine
administered at doses ≤266 mg and bupivacaine HCl administered at doses
≤200 mg for postsurgical analgesia.75 The authors analyzed the pooled efficacy
and safety data from nine controlled multimodal analgesia studies using a single
dose of liposomal bupivacaine or a placebo, administered into the surgical site
before the end of surgery (in patients undergoing inguinal hernia repair, total
knee arthroplasty, hemorrhoidectomy, breast augmentation, or bunionectomy).
The results demonstrated that liposomal bupivacaine administered at doses
≤266 mg in a multimodal setting was associated with statistically significant and
clinically meaningful lower cumulative pain score at 72 hours, delayed and less
consumption of opioids, and fewer ORAEs than bupivacaine HCl.
• Golf, et al, compared wound infiltration with an extended-release liposomal
bupivacaine-based analgesic with placebo for the prevention of pain in 193
25
•
•
•
•
patients after bunionectomy.76 Pain intensity was assessed using a Numeric
Rating Scale (NRS) from time 0 through to 72 hours postoperatively; the primary
efficacy measure was the NRS scores through 24 hours. The patients treated
with liposomal bupivacaine had significantly lower NRS scores, avoided the use
of opioid rescue medication during the first 24 hours, and were pain-free at 2, 4,
8, and 48 hours. The investigators concluded that liposomal bupivacaine provided
extended pain relief and decreased opioid use after bunionectomy in comparison
to a placebo.
Bergese, et al, examined the pooled efficacy data as reflected in cumulative pain
scores from 10 studies in which liposomal bupivacaine was administered via local
wound infiltration.77 A total of 823 patients received liposomal bupivacaine in 10
local wound infiltration studies at doses ranging from 66 mg to 532 mg in five
surgical settings; 446 patients received bupivacaine HCl (at doses from 75 mg to
200 mg); and 190 received placebo. Based on this integrated analysis of multiple
efficacy measures, liposomal bupivacaine appears to be a potentially useful
therapeutic option for prolonged reduction of postsurgical pain in soft tissue and
orthopedic surgeries.
Haas, et al, conducted a study to evaluate the extent and duration of analgesia
after administration of liposomal bupivacaine (LB), a novel formulation of
bupivacaine, compared with bupivacaine HCl given via local infiltration in 100
patients undergoing excisional hemorrhoidectomy.78 The data showed that, for
the LB group, the mean total postoperative opioid consumption was statistically
significantly lower, the median time to first opioid use was longer, and the
incidence of opioid-related adverse events was lower. The authors concluded
that local infiltration with LB resulted in significantly reduced postsurgical pain
compared with bupivacaine HCl in patients after hemorrhoidectomy surgery.
Gorfine, et al, conducted a multicenter study to compare the magnitude and
duration of postoperative analgesia from a single dose of liposomal bupivacaine
extended-release injection with a placebo administered intraoperatively in patients
undergoing hemorrhoidectomy.79 The results demonstrated that in the group
receiving liposomal bupivacaine extended-release:
o Pain intensity scores were significantly lower;
o More patients remained opioid-free from 12 hours to 72 hours after surgery;
o The mean total amount of opioids used through 72 hours was lower;
o The median time to first opioid use was longer; and
o A greater proportion of patients were satisfied with their postsurgical
analgesia.
Naseem, et al, conducted a study to characterize the effect on the corrected
QT interval (QTc) of single subcutaneous (SC) administration of liposomal
bupivacaine in various doses compared with a placebo.80 The results of this
study demonstrated that various doses of liposomal bupivacaine did not show
any clinically significant effect on QTc; a slight shortening of the QTc interval
was observed (more than in the placebo group), which appeared to be dose
dependent; the clinical significance of shortening the QTc interval is not known
26
but is not considered a clinical concern, as QTc shortening has also been
described in published data for other medicines. The authors concluded that this
study shows that bupivacaine given subcutaneously as a new extended-release
formulation in doses of up to 750 mg does not prolong the QT interval and raises
no cardiac concerns.
Table 5 – Results of Studies Pertaining to the Efficacy and Safety of Liposomal
Bupivacaine
Study Author(s)
Cohen
Study Description
39 open colectomy patients:
• 18 patients received PCA with opioids
• 21 patients received multimodal
analgesia therapy, including a
single administration of liposomal
bupivacaine
Results/Conclusions
Multimodal analgesia with
liposomal bupivacaine
resulted in:
• Less opioid consumption
• Lower hospital costs
• Shorter LOS
Dasta, et al
Analysis of the pooled efficacy and safety
data comparing the liposomal bupivacaine
and bupivacaine HCl administered into the
surgical site before the end of surgery in
patients undergoing inguinal hernia repair,
total knee arthroplasty, hemorrhoidectomy,
breast augmentation, or bunionectomy
Liposomal bupivacaine (≤266
mg doses) in a multimodal
setting was associated with:
• Statistically significant
and clinically meaningful
lower pain score at 72
hours
• Delayed and less
consumption of opioids
• Fewer ORAEs
Golf, et al
193 bunionectomy patients:
• 97 patients received liposomal
bupivacaine via wound infiltration
prior to closure
• 96 patients received placebo
More patients treated with
liposomal bupivacaine:
• Had significantly lower
NRS scores
• Avoided use of opioids
during the first 24 hours
• Were pain-free at 2, 4, 8,
48 hours
Bergese, et al
Analysis of pooled efficacy data
across multiple surgical procedures
(hemorrhoidectomy, inguinal hernia
repair, total knee arthroplasty, breast
augmentation, bunionectomy):
• 823 patients received liposomal
bupivacaine in 10 local wound
infiltration studies in five surgical
settings
• 446 patients received bupivacaine
HCl
• 190 patients received placebo
Liposomal bupivacaine
appears to be a potentially
useful therapeutic option
for prolonged reduction of
postsurgical pain in soft tissue
and orthopedic surgeries
27
Haas, et al
100 excisional hemorrhoidectomy patients
randomly assigned to receive (at the end of
the procedure):
• A single dose of bupivacaine HCl with
epinephrine; or
• Liposomal bupivacaine
Liposomal bupivacaine
resulted in:
• Lower postoperative
opioid consumption
• Longer time to first
opioid use
• Lower incidence of
ORAEs
Gorfine, et al
186 hemorrhoidectomy patients receiving
(via wound infiltration intraoperatively)
either:
• A single dose of liposomal
bupivacaine; or
• Placebo
Wound infiltration with
extended-release liposomal
bupivacaine resulted in:
• Significantly lower pain
intensity scores
• More patients remained
opioid-free from 12-72
hours after surgery
• A lower total amount of
opioids used through 72
hours
• A longer time to first
opioid use
• Greater patient
satisfaction with
postsurgical analgesia
Nasseem, et al
Characterize the effect of a single SC
administration of liposomal bupivacaine
compared with placebo on QTc in 49
healthy, nonsmoking, male and female
patients
Various doses of SC
administration of liposomal
bupivacaine did not show any
clinically significant effect on
QTc
Liposomal bupivacaine given
SC in doses of up to 750 mg:
• Does not prolong the QT
interval
• Raises no cardiac
concerns
28
SUMMARY
Pain is a predictable consequence of surgery. If pain is left untreated, it is associated
with significant undesirable physiological, psychological, and economic consequences,
including increased postoperative morbidity, delayed recovery, a delayed return to normal
daily living, the development of chronic pain, reduced patient satisfaction, and increased
lengths of stay and costs of care. National survey data show that approximately 80%
of patients undergoing surgery experience pain that is moderate, severe, or extreme in
intensity for several days or even weeks after the procedure. Effective postsurgical pain
management has taken on greater significance in today’s health care economic climate,
in which hospital reimbursement is tied to the patients’ perceptions of and satisfaction
with the care they receive; pain management is one of the key dimensions of care that
is evaluated by patients. One of the expected outcomes for all surgical patients is they
demonstrate and/or report adequate pain control; therefore, effective postsurgical pain
management with a multimodal approach is essential. Administration of a local anesthetic
via infiltration of the surgical wound is one component of a multimodal approach that
allows for minimally invasive exposure and also results in immediate pain relief, which
has been proven to increase patient satisfaction. Recent advancements have led to
the development of a long-acting formulation of liposomal bupivacaine that is designed
to allow drug diffusion to occur over time following a single administration at the end
of surgery, thereby broadening its potential role as a component of some multimodal
postsurgical pain management regimens. Perioperative nurses should be aware of
these innovative options in local anesthetics and delivery systems in order to manage
postsurgical pain more effectively. Embracing innovative options for postsurgical pain
management can enhance patient safety, recovery, and satisfaction and also results in
measurable economic benefits in today’s challenging health care environment.
29
GLOSSARY
Bupivacaine
A high-potency, long-duration, amide local
anesthetic agent.
Corrected QT Interval (QTc)
The measured QT interval that is transformed
by various heart rate correction formulas; it is
independent of heart rate.
Liposome
A microscopic spherical vesicle consisting
of an aqueous core enclosed in one or more
phospholipid layers; it is used to transport drugs,
enzymes, or other substances to targeted cells or
organs.
Modulation
The process of dampening or amplifying painrelated neural signals; it occurs when descending
pathways to the dorsal horn modulate the activity
of the peripheral nerves by releasing enkephalins
and endorphins.
Multimodal Analgesia
The administration of two or more analgesic
agents that act via different mechanisms
with the goal of improving postsurgical pain
management and reducing the use of opioids and
consequently the associated adverse drug events
in postsurgical patients.
Nociceptors
A group of cells that acts as a sensory receptor
for painful stimuli.
Perception
The subjective experience of pain resulting from
the interaction of transduction, transmission,
modulation, and the psychological aspects of the
individual; it occurs at the level of the brain.
Preemptive Analgesia
An antinociceptive treatment intended to prevent
CNS sensitization to counteract the “wind-up”
phenomenon and alter the overall pain response.
Somatic Pain
Pain that originate in muscles, skeleton, skin; pain
in the parts of the body other than the viscera.
Surgical pain is an example of somatic pain.
30
Transduction
The process by which afferent nerve endings
participate in translating a painful stimulus into
nociceptive impulses; it occurs when mediators,
eg, substance P, serotonin, histamine, and
bradykinin are released at the tissue injury site.
Transmission
The process by which impulses are sent to the
dorsal horn of the spinal cord, and then along
the sensory tracts to the brain; it occurs when
ascending nerves extending from the dorsal horn
of the spinal cord to the brain are stimulated by
the peripheral sensory afferents.
31
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