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Perioperative Pain Management
of Patients Presenting for Cardiac
Surgery
Eric R. Simon, Michelle Kuei, and Patrick Meyer
Abstract Pain following cardiac surgery is often severe and the consequences of
undertreatment may result in significant complications in both the immediate and
extended postoperative period. Improved postoperative pain control may substan-
tially shorten hospital length of stay, decrease postoperative ventilation requirements,
reduce postoperative complications, and improve patient satisfaction. In patients
presenting for cardiac surgery, multidisciplinary and multimodal approaches that
include oral and intravenous analgesics and regional anesthetic techniques represent
techniques worthy of substantial consideration.
Keywords Cardiac surgery
· Postoperative pain · Chronic pain · Regional
anesthesia
· Analgesics
1 Introduction
Death from cardiovascular disease remains the most common cause of worldwide
mortality and many cardiovascular diseases require surgical intervention to provide
definitive treatment. Pain after cardiac surgery is common, and despite multiple
analgesic strategies that might provide substantial relief, is frequently moderate or
severe in intensity. Uncontrolled pain following cardiac surgery may lead to signif-
icant complications for the patient in the immediate and extended postoperative
period. Efforts to provide adequate pain control in patients requiring cardiac surgery
should be a high priority for the entire perioperative care team and multidisciplinary
E. R. Simon (
B
) · P. Meyer
School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
e-mail: esimon2@wisc.edu
P. Meyer
e-mail: psmeyer@wisc.edu
M. Kuei
Boulder Valley Anesthesiology, Boulder, CO, USA
e-mail: mkuei@bvapllc.com
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A. Abd-Elsayed and K. Schroeder (eds.), Perioperative Pain Management,
https://doi.org/10.1007/978-3-031-67648-2_22
339
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340 E. R. Simon et al.
and multimodal approaches are more likely to provide meaningful perioperative
analgesia.
2 Most Common Conditions in Adults Requiring Cardiac
Surgery
Coronary artery bypass grafting (CABG) and heart valve surgeries are the most
commonly performed procedures in cardiac surgical patients across the world [1].
Dramatic advancements in surgical skills and anesthetic techniques have allowed for
increasingly complex surgeries in older patients with a multitude of comorbidities
[2]. Historically, these procedures have always been performed through a midline
sternotomy or a thoracotomy incision. However, efforts to minimize the postoperative
pain experienced by cardiac surgical patients have resulted in the development of
minimally invasive techniques including mini-sternotomy, mini-thoracotomy, and
fully endoscopic surgery via port sites.
3 Acute Postoperative Pain
Pain after cardiac surgery is multifactorial and may be of musculoskeletal, visceral, or
neuropathic origin. Most commonly, postoperative pain originates from myofascial
structures such as muscle, bone, tendon, and ligament that are disrupted during
sternotomy and surgical dissection. Additionally, sternal retraction may result in
fractured ribs, dislocation of the costochondral junction, or costochondritis [3]. Other
causes of musculoskeletal postoperative pain in the cardiac surgical patient include
surgical positioning injuries or ancillary procedures requiring additional incisions,
such as saphenous vein harvest or axillary artery cutdown [4].
Visceral cardiac pain is transmitted to the central nervous system via the vagus
nerve, cervical sympathetic chain, and upper-thoracic sympathetic ganglia. Neuro-
pathic pain after cardiac surgery is attributed to traumatization of the intercostal
nerves that occurs when the intercostal space is opened. Postoperative pleural drains
can intensify visceral pain originating from the parietal pleura through intercostal and
phrenic nerve innervation [5]. Dissection of the internal mammary artery can induce
an irritative state and neuritis that can cause significant pain following coronary artery
bypass surgery [6].
The severity of pain after cardiac surgery is significant, with 30–75% of patients
reporting at least moderate acute pain following these surgical procedures [4]. Post-
operative pain is most severe during the first 24–48 h and generally decreases by
postoperative day three [1]. A detailed analysis of pain evolution following cardiac
surgery demonstrates that pain perception transitions from incisional, thoracic pain
immediately after surgery to musculoskeletal pain elsewhere. Common sources of
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Perioperative Pain Management of Patients Presenting for Cardiac Surgery 341
delayed pain complaints are numerous but include lower extremity pain after saphe-
nous vein harvest or back pain related to positioning and prolonged procedures [4].
The median duration of pain following coronary artery bypass surgery is five days
and is extended to six days for patients who underwent valve surgery [7]. Optimal
pain management should consider the specific cause, location, and timing of pain
foci to maximize successful outcomes in the cardiac surgical patient.
Risk factors for acute pain after cardiac surgery vary depending on the specific
study, but generally include location and extent of the incision (thoracotomy),
younger age (< 60 years), and prolonged surgery (> 2 h) [8]. Other studies have
associated the use of cardiopulmonary bypass with slightly higher pain levels, poten-
tially attributed to the induction of the systemic inflammatory response syndrome
[9]. Additionally, some studies suggest that women report higher pain intensities and
a significantly higher number of painful areas compared to men after cardiac surgery
[10, 11]. Elevated preoperative anxiety has been shown to increase the sensation of
pain in the postoperative period [12, 13], more so in men than women [14]. The
effects of ethnic, cultural, and socioeconomic factors on the perception of postoper-
ative pain have been demonstrated in some preliminary studies but warrant further
investigation [15].
Patients undergoing cardiac surgery pose specific pain management challenges
during the postoperative period due to a variety of both patient and procedural factors.
Pain assessment is the first important step in effective treatment. However, it may be
difficult for providers to assess pain following cardiac surgery secondary to ongoing
intubation and sedation [16]. Postoperative delirium is common and may compound
difficulties associated with pain assessment and treatment. Fortunately, a variety
of patient assessment tools have been recently developed that serve to aid in the
evaluation of postoperative pain, agitation, and delirium in intensive care unit (ICU)
patients, and many of these have been specifically validated in the cardiac surgery
population [17].
Additionally, patient beliefs about expected pain intensity and pain management
may impact the efficacy of management by the postoperative care team. In a study of
564 patients scheduled for cardiac surgery, Cogan et al. showed that a considerable
number of patients had negative misconceptions related to the treatment of pain after
surgery that likely led to suboptimal treatment and possibly worse outcomes [18].
The authors concluded that there is an absolute necessity to provide pain education
to patients undergoing cardiac surgery as this may improve patient expectations,
satisfaction, and postoperative outcomes.
Physiological pain is one of the main defense mechanisms of the human body.
Postoperative pain, however, is a consequence of a planned traumatic injury and
therefore does not play a role in warning and defense. Instead, it leads to the devel-
opment of a number of adverse pathophysiological processes instigated by nociceptor
stimulation [19]. Of particular concern is the effect of pain on the respiratory system.
Pain leads to reflex muscular tension and splinting, impairing the patient’s ability to
breathe leading to shortness of breath and a reduction in tidal volume, vital capacity,
functional residual capacity, and pulmonary compliance [20]. Pain also impairs the
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342 E. R. Simon et al.
ability to expectorate secretions that accumulate in the bronchial tree resulting in
atelectasis, hypoxemia, and pneumonia [21].
Uncontrolled pain after cardiac surgery also results in activation of the sympa-
thetic nervous system leading to increased heart rate, heart contractility, and blood
pressure, all of which increase the risk of myocardial ischemia. Elevated circulating
catecholamines increase the risk of arrhythmias such as atrial fibrillation. Poorly
controlled pain results in reductions in peripheral blood flow and venous stasis,
which predisposes the patient to the development of deep vein thrombosis particu-
larly in the setting of postoperative immobilization. Activation of the sympathetic
nervous system also impairs the mobility of the gastrointestinal tract and bladder,
potentially leading to urinary r etention, constipation, and ileus [22].
Detrimental changes in the endocrine system also occur [23]. There are increased
circulating levels of cortisol, antidiuretic hormone, corticotropic hormone, renin,
angiotensin, and aldosterone. Conversely, there are decreased circulating levels of
insulin which leads to a catabolic state. Prolonged nociceptive stimulation can lead
to suppression of the patient’s immune system, increasing the risk of infections and
impairing wound healing. Finally, severe uncontrolled pain has detrimental psycho-
logical effects for the patient, leading to anxiety, depression, and sleep disorders
[24].
4 Chronic Pain After Cardiac Surgery
Pain after cardiac surgery may persist long enough that it loses its warning func-
tion and transitions into a pathologic state of chronic postoperative pain. Chronic
pain most often arises following traumatic or inflammatory nerve injury which then
establishes a neuropathic pain phenotype [25]. Diagnostic criteria for chronic pain
typically include at least 3–6 months of consistent pain symptomology and pain
of adequate severity to significantly impact a patient’s quality of life [26]. Chronic
pain after cardiac surgery is often underappreciated, as 21–55% of patients develop
chronic pain syndromes following cardiac surgery [3, 27]. Higher levels of acute
pain following cardiac surgery are associated with a 3.5-fold increased likelihood of
chronic postoperative pain development [3]. Other risk factors for chronic postoper-
ative pain development include depression, psychological vulnerability, high levels
of stress, more extensive surgery, and prolonged surgery [28].
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Perioperative Pain Management of Patients Presenting for Cardiac Surgery 343
5 Pharmacologic Methods of Pain Control After Cardiac
Surgery
Over the past decade, the emergence of enhanced recovery after surgery (ERAS) for
cardiac surgery programs has prompted care teams to explore unique options for the
management of postoperative pain in place of high-dose opioid administration. This
section will explore pharmacological modalities that may be utilized to assist with
pain control in the cardiac surgery patient.
Opioids
High dose opioids have historically been utilized in cardiac surgery patients to provide
perioperative analgesia and intraoperative anesthesia. Although opioids have no anal-
gesic ceiling effect, their use is mainly limited by the accumulation of side effects
that are encountered with dose escalations. These side effects include somnolence,
respiratory depression, hypotension, urinary retention, nausea and slowed gastroin-
testinal transport which can result in constipation and postoperative ileus. In cardiac
surgery patients, the judicious use of opioids is necessary to avoid excess sedation and
prolonged intubation [29]. Nonopioid analgesic adjuncts are important to minimize
opioid use and enhance recovery following cardiac surgery and their use represents
the focus of the remainder of this section.
Acetaminophen
Acetaminophen produces its analgesic effect by inhibiting central prostaglandin
synthesis [30]. Although this medication has some similarities to a non-steroidal anti-
inflammatory agent, acetaminophen is not felt to have an adverse effect on platelets
or gastric mucosa [31, 32]. The perioperative analgesic effect of acetaminophen
has been demonstrated in numerous randomized controlled trials and meta-analyses.
In cardiac surgery, acetaminophen has been shown to reduce perioperative opioid
use and improve overall pain scores [33]. When utilized in combination with other
sedatives in older adults following cardiac surgery, a randomized controlled trial
demonstrated a decreased postoperative opioid requirement and a lower incidence
of in-hospital delirium in those patients who received scheduled acetaminophen
along with their sedative regimen [34]. Acetaminophen can be administered orally,
rectally, or intravenously. The daily dose of acetaminophen is generally limited to
3000–4000 mg per day to decrease hepatotoxicity risk.
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344 E. R. Simon et al.
Non-steroidal Anti-inflammatory Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medication used
widely for their analgesic, antipyretic and anti-inflammatory effects. The mechanism
of action of NSAIDs is via inhibition of the enzyme cyclooxygenase. This inhibition
can impair production of thromboxanes, prostaglandins and prostacyclins, which
together account for their analgesic efficacy as well as their side effects. Well known
side effects i nclude an increased risk of gastric mucosal damage, renal dysfunc-
tion, adverse cardiovascular events and hematologic effects secondary to antiplatelet
activity [35]. NSAIDs are generally avoided following cardiac surgery in the United
States due to the Food and Drug Administration (FDA) black box warning describing
the potential for NSAIDs to induce adverse cardiovascular events, including myocar-
dial infarction, cardiac arrest, stroke and pulmonary embolism [36–38]. NSAID use
following cardiac surgery has also been associated with postoperative renal dysfunc-
tion [39]. Despite these concerns, the use of NSAIDs following cardiac surgery
may represent an appropriate analgesic adjunct in select patients [40]. Patients with
normal renal function and at low risk of perioperative kidney injury and those in
whom there is a low bleeding risk may represent reasonable candidates for judicious
NSAID therapy.
Gabapentinoids
The gabapentinoid drugs gabapentin and pregabalin are believed to exert their modu-
lation of pain via blockade of a subunit of voltage-gated calcium channels. Gabapenti-
noids depress excitatory input onto dorsal horn neurons, stimulate descending inhi-
bition, and have anti-inflammatory actions via incompletely understood mechanisms
[41, 42]. Known side effects of these medications include sedation, respiratory
depression, dizziness, and visual disturbances which can be more pronounced in
the setting of renal dysfunction. Multiple studies evaluating the analgesic impact of
perioperative administration of gabapentinoid drugs have shown conflicting results.
A large meta-analysis of 281 randomized controlled trials comparing gabapentinoids
with controls demonstrated no clinically meaningful difference in acute, subacute
or chronic pain [43]. In coronary artery bypass grafting surgery, Menda et al. found
significantly lower pain scores, opioid requirements and postoperative nausea and
vomiting in patients who received gabapentin 600 mg preoperatively compared to
placebo. However, the gabapentin group required longer postoperative ventilation
and more patients were found to be overly sedated [44]. In another randomized
controlled trial evaluating gabapentinoid administration in CABG patients, prega-
balin administration failed to reduce opioid requirements despite reducing postop-
erative pain scores [45]. Interestingly, there may be a role for the use of pregabalin
to reduce the prevalence of persistent postsurgical pain after cardiac surgery [46].
Gabapentinoids appear to have potential as a non-opioid adjunct, but optimal dosing
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Perioperative Pain Management of Patients Presenting for Cardiac Surgery 345
regimens must be evaluated further to maximize analgesia and minimize side effects.
The FDA has issued a warning for respiratory depression when these medications are
utilized along with other central nervous system depressants s uch as opioids. There
is currently insufficient evidence to recommend widespread utilization in cardiac
surgery patients for postoperative pain control [47].
Ketamine
Ketamine is a noncompetitive N-methyl-D-aspartate (NMDA) and glutamate
receptor antagonist that can be utilized as a dissociative anesthetic. When used in
subanesthetic doses, it can serve as an analgesic adjunct that reduces opiate-induced
hyperalgesia and improves pain control [48]. The most common side-effects include
dizziness, drowsiness, confusion, and hallucinations that become more common at
higher doses. In cardiac surgery patients, a ketamine infusion has been shown to
result in a diminished opioid requirement and improved patient satisfaction despite
not altering pain scores [49]. Nesher et al. similarly demonstrated that postoperative
ketamine infusions were associated with a reduction in postoperative opioid require-
ments i n patients who underwent thoracotomy, including minimally invasive CABG
[50]. There is evidence that an intraoperative infusion of ketamine during cardiac
surgery may attenuate the surgical stress response following cardiopulmonary bypass
with several clinical trials showing decreased inflammatory biomarkers in patients
receiving ketamine [51]. There is some evidence that intraoperative ketamine admin-
istration may be associated with a lower incidence of postoperative delirium [52],
but this effect has not been consistently demonstrated in other major surgeries [53].
The potential benefits, relative absence of frequent serious side effects, and hemody-
namic stability associated with ketamine administration has resulted in a significant
increase in the use of this analgesic adjunct in cardiac surgery patients.
Dexmedetomidine
Dexmedetomidine is a highly selective alpha-2 adrenergic receptor agonist that is
associated with sedative and analgesic effects. Clinical attributes associated with
dexmedetomidine infusions include sedation, sympatholysis, analgesia, anxiolysis
and maintenance of respiratory function. The widespread effects of dexmedetomi-
dine can be attributed to the diverse and well-distributed sites of action in the body.
Most of the analgesic effects relevant to dexmedetomidine administration occur via
its agonist activity on alpha-2 adrenergic receptors in the spinal cord, which reduces
transmission of nociceptive signals [54]. A systematic review of twelve clinical
trials evaluating the clinical effect of dexmedetomidine on pain following cardio-
thoracic surgery supports routine administration secondary t o observed reductions
in postoperative pain and analgesic requirements for up to 24 h following surgery
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346 E. R. Simon et al.
[55]. Several other studies have shown a wide spectrum of beneficial effects associ-
ated with dexmedetomidine administration in cardiac surgery patients, including a
decrease in postoperative mortality and delirium [56], as well as a reduction in ICU
length of stay [57]. Other studies have found no difference in the rate of delirium or
ICU length of stay when dexmedetomidine or propofol were used for postoperative
sedation but did demonstrate decreased opioid requirements in patients receiving
dexmedetomidine [34]. Given its ability to act as a sedative and potent analgesic,
dexmedetomidine certainly has a role in the perioperative care of cardiac surgery
patients.
Steroids
Surgery causes tissue injury and induces both a local and systemic inflammatory
response. Corticosteroids have been found to possess analgesic benefits following
surgery, likely due to their potent anti-inflammatory and immunosuppressive effects.
Steroid use in noncardiac surgery has been extensively studied, with a large meta-
analysis of randomized controlled trials demonstrating dexamethasone doses more
than 0.1 mg/kg to be an effective adjunct to reduce postoperative pain and opioid
consumptions following surgery [58]. The degree of analgesic benefit associated with
perioperative steroid administration appears to vary by surgery type and appears to
be most effective in orthopedic, oral and ear, nose and throat (ENT) surgery [59].
Randomized controlled trial data has previously demonstrated that two intraoper-
ative doses of 250 mg of methylprednisolone did not improve postoperative anal-
gesia after cardiac surgery [60]. Common concerns regarding steroid administration
include a theoretical increased infection risk profile, impaired wound healing or an
increased risk of gastrointestinal bleeding secondary to immune and inflammatory
modulating properties. Currently, the best evidence supporting the safety of prophy-
lactic corticosteroid administration on adult cardiac surgery outcomes is provided
by two large randomized-controlled trials which found no difference in mortality
or major morbidity [61]. Further investigation into the analgesic impact of different
doses and types of steroids in cardiac surgery patients is warranted to guide future
use as an analgesic adjunct.
Magnesium
Magnesium has been found to have antinociceptive properties, largely through
its antagonist action at the N-methyl-d-aspartate (NMDA) receptor [62]. Given
the significant role of NMDA receptors in pain transduction, many studies have
evaluated this agent for a potential role in providing perioperative analgesia. In
cardiac surgery, a randomized study found a bolus dose and subsequent contin-
uous infusion of magnesium gluconate decreased remifentanil consumption without
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