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222 C. Hasken et al.
intrapleural anesthesia, and systemic pain medications for post-thoracotomy anal-
gesia [55]. They found continuous PVB to be as effective as TEA for analgesic
control but with a decreased risk of significant hypotension. Both TEA and PVB
were superior to intrathecal and intercostal blocks. Systemic pain medications alone
and intrapleural anesthesia were the least effective options for pain control [55].
Aside from postoperative chest wall pain, patients with traumatic rib fractures
may also benefit from regional anesthesia. One small randomized controlled trial
compared the use of continuous PVB and TEA for patients with three or more
unilateral rib fractures [56]. Both options demonstrated similar analgesic effects,
pulmonary complication incidence, opioid requirements, and ICU and hospital
lengths of stay. More hypotension was noted in the TEA group, suggesting PVB
may be a superior option for patients with hemodynamic instability [56]. In another
randomized study, Elawamy et al. compared intermittent PVB and intermittent
erector spinae plane (ESP) blocks for patients with multiple unilateral rib fractures
and found no difference in pain reduction or time to opioid rescue request [57].
The investigators did not place continuous catheters but instead repeated single shot
blocks as needed, so these results may not be generalizable to patients receiving
continuous blocks. Alternatively, for interventions such as chest tube insertion,
administering local anesthetic at the site or performing a single shot intercostal
nerve block may provide analgesic benefit [43]. For any chest wall nerve block,
there is a small risk of pneumothorax or rapid uptake of local anesthetic by intercostal
vasculature [58].
For major abdominal surgery, alternatives to epidural anesthesia include
transversus abdominus plane (TAP) blocks and rectus sheath blocks. TAP blocks can
be helpful for analgesia at the level of T10 or below, but subcostal placement may
provide higher coverage [43]. Patients undergoing surgeries including open chole-
cystectomy, hepatic resection, and cesarean section may benefit from TAP blocks.
Rectus sheath blocks theoretically provide s uperior analgesia for vertical midline
incisions of the upper and lower abdomen such as for an exploratory laparotomy
[43]. Despite promising evidence that perioperative TAP and rectus sheath blocks
can improve pain control, little is known regarding their use in critically ill patients.
For open nephrectomy patients, Capdevila et al. found that continuous surgical site
analgesia with catheters placed by the surgeons at the end of the case were equivalent
to TEA for improved pain control and reduction in opioid consumption compared to
patients randomized to systemic opioid analgesia [47]. Surgical site catheters were
also associated with reduced pain at one month postoperatively, whereas TEA did
not show this benefit [47].
For peripheral nerve blocks, a meta-analysis of 603 patients reported improved
pain control at 24 hours, 48 hours, and 72 hours for all locations with continuous
catheter infusions compared to those receiving only systemic opioids [59]. This anal-
ysis included both upper extremity and lower extremity nerve blocks [59]. Patients
were more satisfied with analgesia in the nerve block group compared to the opioid
group, and patients with blocks required less opioid for adequate analgesia [59].
Blocks can be performed for postoperative pain, traumatic injuries, and burn injuries
with the same precautions as for perioperative block placement. For example, in
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Pain Management Considerations in Critical Care 223
patients with a tenuous respiratory status, an interscalene nerve block should be
avoided due to ipsilateral phrenic nerve paralysis [43]. The use of peripheral nerve
blocks in the ICU may in turn reduce ICU length of stay and hospital length of stay
by improving patient mobility and participation in physical therapy [58]. However,
peripheral nerve block administration specifically for critically ill patients requires
additional consideration to determine patient selection, medication dosing, efficacy,
and safety.
16 Non-pharmacological Options
From music therapy to virtual reality, non-pharmacological interventions for anal-
gesia in the ICU vary widely depending on hospital resources and availability.
Hypnosis, distraction, and virtual reality may provide some analgesic benefit
[60]. Other options such as music therapy, listening to natural sounds, and
emotional support can help improve critically ill patients’ comfort. At advanced
centers acupuncture, massage, or passive exercise are available for patients. In a
scoping review by Sandvik et al., evidence suggests that the most promising non-
pharmacological interventions for analgesia in the ICU are acupuncture, hypnosis,
and listening to natural sounds [60]. In a randomized trial specifically assessing
the use of virtual reality and hypnosis for postoperative cardiac surgery patients in
the ICU, Rousseaux et al. evaluated four modalities for their impact on recovery
and analgesia—virtual reality, hypnosis, virtual reality plus hypnosis, and no inter-
vention. All interventions showed a reduction in anxiety but no improvement in
pain postoperatively [61]. There was no significant difference in opioid consumption
between intervention groups [61]. Due to the limited evidence supporting the use
of non-pharmacological interventions for analgesia, none of these interventions are
currently recommended for routine use, and more data is needed to better under-
stand the effects of each intervention. Availability of these modalities are limited by
expense and local resources. However, these modalities may be useful in critically
ill patients with limited analgesic options and may provide an additional method to
alleviate anxiety and improve coping skills for pain [12].
17 The Multidisciplinary Approach to Pain Management
in the ICU
The healthcare team in the ICU must balance the important need for pain manage-
ment while simultaneously stabilizing and treating the critically ill patient, which
requires forethought to counteract or limit the potential adverse effects associated
with the administration of analgesic therapies. For this reason, pain management in
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224 C. Hasken et al.
the intensive care unit is a multidisciplinary challenge involving the multidisciplinary
ICU team, the surgical team, and occasionally an expert acute pain team.
As one notable example, intensivists and surgeons often grapple with whether to
place an epidural for patients with refractory pain who would otherwise benefit from
aggressive anticoagulation. For critically ill patients with traumatic rib fractures,
placement of an epidural is demonstrated in multiple studies to decrease pulmonary
complications in specific patient populations [62, 63]. At the same time, patients with
traumatic injuries develop hypercoagulability, with a conservative risk for develop-
ment of deep venous thrombosis (DVT) of 7–12% [64]. The optimal prophylaxis
for DVT in trauma patients is twice daily low molecular weight heparin. However,
this thromboprophylaxis dose has been demonstrated to increase the risk of epidural
hematoma and is not recommended with an indwelling epidural catheter according
to the American Society of Regional Anesthesia and Pain Medicine guidelines [65].
Accordingly,an individualized and multidisciplinary decision must be made whether
to prioritize optimal analgesia at the expense of less effective thromboprophylaxis. A
similar multidisciplinary approach is required when considering neuraxial analgesia
for patients with severe surgical pain after cardiac surgery, as this patient population
commonly has postoperative coagulation deficits from cardiopulmonary bypass or
may require anticoagulation for a mechanical valve replacement.
A similar collaborative approach is required to manage the hemodynamic effects
of epidural analgesia in the immediate post-operative state. For large abdominal
surgeries with fragile anastomoses such as a Whipple or esophagectomy, increased
tissue edema and vasopressor use can threaten anastomosis viability [66–68]. Local
anesthetic infused through thoracic epidurals causes an obligate sympathectomy,
which can lead to increased fluid administration or vasopressor use to maintain
adequate blood pressure. A balanced decision must thus be made between the surgical
team, who have intricate knowledge of the patient’s operative anatomy, and the
multidisciplinary intensive care team, regarding the optimal dose and rate of the
thoracic epidural.
Even the use of standard intravenous opioid analgesia requires careful consider-
ation in certain critically ill patient populations, as is the case for liver transplant
recipients hospitalized in the intensive care unit. Liver transplant recipients experi-
ence significant pain following surgery due to a large subcostal abdominal incision
and prolonged surgical retraction [69]. Adequately treating this pain is important to
allow for early liberation from the ventilator and sedation. However, nearly 25% of
liver transplant patients experience early autograft dysfunction [70]. Since all opioids
are hepatically metabolized, a liver transplant patient’s circulating opioid level is
intricately tied to graft function. Because neuraxial analgesia is rarely an option due
to coagulopathy, the surgeons and ICU team must use their combined knowledge of
the patient’s pain level and predicted liver recovery in order to carefully dose opioids.
At many institutions, a dedicated acute pain service (APS) is available for consul-
tation to assist with the management of challenging or refractory pain in the inten-
sive care unit. This expert service is typically lead by an anesthesiologist who
has undergone additional fellowship training in acute pain management, including
regional procedures and novel pharmacologic approaches. Services offered by an
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Pain Management Considerations in Critical Care 225
APS typically include neuraxial and regional interventions, guidance on adjunc-
tive medical therapies such as intravenous ketamine and lidocaine infusions, and
assistance managing patients with preexisting chronic pain. Multiple studies have
corroborated the benefits of an APS for the management of post-operative patients,
noting lower pain scores, improved patient satisfaction, and reduced post-operative
opioid use [71, 72]. Since the APS has the ability to follow patients throughout their
hospital stay, involving this expert team early in the intensive care hospitalization
allows for continuity in pain management once the patient is stabilized.
18 Future Directions in Critical Care Pain Management
The large cohort of survivors of critical illness from the 2019 coronavirus pandemic
has highlighted the need to address the significant psychological morbidity that is
associated with surviving critical illness, for which the experience of pain plays
a major role. One third of critical illness survivors experience chronic pain after
discharge [73]. Additionally, one quarter of critical illness survivors experience post-
traumatic stress disorder, with the memory of severe pain during an intensive care
hospitalization significantly increasing this risk [74]. The physiologic mechanism
for post-ICU chronic pain has not been fully elucidated, but is s uspected to involve
central sensitization from repeated noxious stimuli, similar to post-surgical chronic
pain, as well as the impact of chronic inflammation on nociceptors [73]. Retrospective
studies have identified risk factors for developing chronic pain following critical
illness, including severe sepsis, high medical morbidity, and prolonged ICU length
of stay [75–77]. Understanding that these risk factors generally align with the most
critical subset of intensive care patients, exploring methods to mitigate the long-
term risk of developing chronic pain in this population represents the next important
frontier of analgesic therapy in the intensive care unit.
Two promising areas of research for the prevention of chronic pain following
critical illness are “transitional pain clinics” and early mobilization. Transitional pain
clinics are a multidisciplinary service provided to patients for three to six months
following ICU discharge focused on preventing chronic pain [78]. The clinics provide
psychological support and therapeutic education using a multi-disciplinary staff.
They are modeled from similar clinics that have been established to successfully
manage post-surgical pain [ 78]. Additionally, early physical therapy in the intensive
care unit improves short-term quality of life and peripheral muscle strength [79, 80].
Given the interplay of mental health, chronic pain, and mobility, investigators are
actively studying the benefits of early physical therapy to prevent chronic pain in
critically ill patients.
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226 C. Hasken et al.
19 Key Takeaways
•
Pain is ubiquitous in critically ill patients and often multi-factorial. Pain in criti-
cally ill patients results from injuries, such as recent surgery or trauma, as well as
routine intensive care procedures, such as repositioning and tracheal suctioning.
•
Effective pain management in critically ill patients has been demonstrated to
decrease the duration of mechanical ventilation and improve in-hospital mortality.
Conversely, inadequate analgesia can have significant adverse consequences
including increased myocardial demand and worsened delirium.
•
Often critically ill patients cannot adequately communicate their pain due to phar-
macologic sedation, delirium, or encephalopathy. For patients unable to commu-
nicate, clinical guidelines recommend using one of two validated tools—the
Behavioral Pain Score (BPS) or the Critical Care Pain Observation Tool (CPOT).
•
Unfortunately, neither the BPS nor the CPOT has been validated in critically ill
patients with delirium, who comprise 26–78% of patients in intensive care units.
For this patient population, clinical guidelines recommend using an “analgoseda-
tion” approach that prioritizes treatment of pain with an analgesic agent before
employing sedative agents.
•
Acetaminophen is a proven analgesic adjunct in critically ill patients with multiple
modes of administration (oral, intravenous, per rectum). Its administration
requires attention to enteric absorption and liver function.
•
NSAIDs are not recommended for routine use in critically ill patients due to
mixed evidence of efficacy and potential for adverse effects, including platelet
dysfunction, kidney injury, and gastrointestinal irritation. However, they remain
a helpful pain adjunct for the appropriate patient.
•
Gabapentin, pregabalin, and carbamazepine are neuropathic pain medicines with
a demonstrated opioid sparing effect in patients with Guillan-Barre syndrome and
post-cardiothoracic surgery. These neuropathic pain medicines are recommended
for use in critically ill patients, but notably require enteral administration.
•
Opioids remain the mainstay of analgesia in critically ill patients, despite multiple
adverse effects. Notably, patients on chronic opioid therapy require a dosing
schedule that considers their baseline opioid regimen plus their requirement for
acute pain. Methadone, sufentanil, and nalbuphine are emerging opioid therapies
actively under study in critically ill patients.
•
Ketamine is an NMDA antagonist that is rapidly growing as an analgesic agent for
critically ill patients due to its opioid-sparing effect and lack of respiratory depres-
sion. Concerns remain about its potential to cause hallucinations and delirium,
and the evidence on this topic is mixed.
•
There is limited evidence to support the use of systemic lidocaine for analgesia in
critically ill patients outside of the colorectal surgery population. Topical lidocaine
patches have little downside and some evidence for reducing opioid requirements.
•
Epidurals provide excellent analgesia in critically ill patients, with certain studies
also demonstrating improved clinical outcomes in post-surgical patients and
pancreatitis patients. The risk of epidural hematoma can be increased in patients
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Pain Management Considerations in Critical Care 227
undergoing liver surgery due to complex coagulopathy and cardiac surgery
patients receiving large heparin boluses for cardiopulmonary bypass. Viable alter-
natives to epidural analgesia include paravertebral blocks, erector spinae blocks,
TAP blocks, and peripheral nerve blocks.
•
Due to the adverse effects of epidurals and many analgesic medications, pain
management in the intensive care unit is necessarily a multidisciplinary issue.
Many institutions offer a dedicated acute pain service that provides assistance
with regional procedures and medication management for refractory pain.
•
Up to one third of patients discharged from the intensive care unit experience long-
term chronic pain. In addition to effective analgesia, transitional pain clinics and
early mobilization offer two promising strategies currently under investigation to
mitigate the development of chronic pain in ICU survivors.
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