Use of Regional Anesthesia With Liposomal Bupivacaine For Palliation of Pain at the End of Life

Introduction

The administration of regional anesthesia for the purpose of palliative care is a field that remains mostly uninvestigated. The sparse data collected in this area have primarily focused on specific administration techniques, without much emphasis on subjective pain relief or comfort levels during end-of-life palliation. Although the technical aspects and correlated benefits of perioperative placement of regional nerve blocks have been well validated, it may be argued that improving the comfort levels in patients’ final hours of life is still an underappreciated utility of regional anesthesia. Defining an accurate, consistent and objective method to measure tremendously subjective variables such as comfort and pain could prove challenging, which could explain the aforementioned nescience on the topic.

Clinical Course

This case study documents the care of an 81-year-old woman with a history of tobacco dependency and medical noncompliance. She presented to the emergency department of a community hospital with complaints of abdominal pain, nausea and emesis.

Initial vital signs showed tachycardia, tachypnea and hypertension, along with moderate hypoxia. Her physical exam demonstrated a distended abdomen that was tender to palpation diffusely with associated diffuse guarding. Laboratory studies were positive for a mild leukocytosis of 12,700/uL with a left shift including bandemia. The patient had anion gap acidosis due to a mildly elevated lactate level of 2.1 mmol/L. Her procalcitonin level was very elevated, at greater than 200 ng/mL. She had acute kidney injury with a creatinine level of 2.76 mg/dL and an estimated glomerular filtration rate of 16 mL/min/1.73 m2. A CT scan of the abdomen and pelvis demonstrated free air in the left upper quadrant, as well as mesenteric inflammation, which was concerning for peritonitis. The patient was admitted for the surgical management of acute peritonitis due to a perforated viscus, sepsis and acute renal failure.

In the emergency department, she was treated with aggressive fluid resuscitation and IV antibiotics. The patient was promptly transferred to the OR for an emergency exploratory laparotomy. A central venous line and arterial line were placed during induction of anesthesia. The patient then underwent an uncomplicated left hemicolectomy with transverse colostomy. For postoperative pain control, she was given an intrathecal injection of fentanyl and preservative-free morphine. In addition, bilateral transversus abdominis plane (TAP) blocks with bupivacaine plus liposomal bupivacaine (Exparel, Pacira) were placed under ultrasound guidance.

At the conclusion of the operation, the patient was transported to the ICU sedated on dexmedetomidine, mechanically ventilated, and with norepinephrine titration. Antibiotics were continued. A bedside point-of-care echocardiogram performed by the anesthesiologist revealed good contraction, no wall motion or valvular abnormalities, a plump inferior vena cava, and no major chest effusions.

Postoperative Day 1

The patient remained hemodynamically stable on norepinephrine, aside from one episode of nonsustained ventricular tachycardia. She remained chemically sedated on mechanical ventilation. She underwent a formal echocardiogram, which revealed mild global hypokinesis with an estimated ejection fraction of 50% to 55%. Unfortunately, the patient had a worsening of her metabolic acidosis, and she maintained an oliguric state despite aggressive volume resuscitation and titration of blood pressures to maintain mean arterial pressure greater than 65 mm Hg.

Family discussions were held with her adult children (her health care powers of attorney), who held a realistic perspective of her grave condition and very guarded prognosis. They elected to pursue no further advanced procedures but desired to continue with all supportive measures, hoping for improvement in their mother’s condition.

Postoperative Day 2

The patient developed an acutely ischemic right lower extremity, which was immediately concerning, given her history of peripheral vascular disease. Further workup with a Doppler study revealed no flow distal to the iliac artery. A vascular surgeon was consulted and, given her worsening renal failure, shock state and overall frail physiologic condition, believed that revascularization attempts in the OR/interventional radiology suite would be immediately life-threatening. After a multidisciplinary family discussion, family members opted to transition her care to comfort measures as a sole focus.

After the decision was made to pivot her care toward palliation, dexmedetomidine was weaned with plans to extubate and allow her to spend time conversing with family. After family had arrived from out of town, the patient was extubated to a heated high-flow oxygen system. The dexmedetomidine was weaned, and the patient became increasingly lucid.

The patient verbalized intense pain in her right leg, but no abdominal pain (presumably residual analgesia from the intrathecal and TAP blocks). At this point in time, the patient was prepared for peripheral nerve block placement with verbal consent from the patient, as well as written consent from her son, her health care power of attorney.

A combination of two regional nerve blocks under ultrasound guidance was placed: femoral and sciatic nerve blocks. These blocks were placed using the standard ultrasound-guided, nerve-stimulated techniques as if being performed for a perioperative regional anesthetic. A combination of bupivacaine 0.25% with epinephrine 1:200,000 plus liposomal bupivacaine was administered for these two blocks. Intralipid (IV fat emulsion, Baxter Healthcare) was kept at bedside in the event any signs of local anesthetic toxicity developed. Of note, the patient was not ambulatory, so there was no concern with fall risk associated with a prolonged motor blockade. There were no signs of local anesthetic toxicity, and within a matter of minutes after placement of these peripheral nerve blocks, the patient verbalized that her leg pain was resolved and that she was quite comfortable.

As her death was imminent and expected within the following 24 to 48 hours, the patient was transferred from the critical care unit to a palliative care suite, which offered the patient and her family a much more private and spacious room for visiting during her final hours of life.

Postoperative Day 3

The patient began to develop some abdominal pain and dyspnea in the final few hours of life that necessitated a morphine titration. She stated that her ischemic leg was not causing her any pain. She survived approximately 30 hours after placement of the regional nerve blocks and did not have any recurrence of ischemic pain in this extremity for the rest of her hospital course. During the 30-hour interval between the placement of regional anesthesia and her death, she was able to visit coherently with her family members in relative comfort for most of this period, until the abdominal pain and dyspnea worsened. This would likely not have been possible without the novel use of a regional anesthetic technique.

Controversial Issues to Address

There has not been a great deal of conversation about peripheral nerve blocks used for palliative measures. Some may consider this application controversial, as it is not the “traditional” application toward acute surgical pain management. However, this case demonstrates at least one instance in which it was beneficial for the patient in the final hours of life.

The use of liposomal bupivacaine for a regional block involving motor nerve distribution is also a controversial topic, due to its extended action reducing motor strength. However, this patient was clearly nonambulatory, so the risk for falls from a prolonged motor block of a lower extremity was unwarranted. The end point of these blocks was simply to provide her with adequate nonopioid analgesia for the duration of her remaining life; this end point was achieved.

Liposomal bupivacaine in the femoral and sciatic regional blocks was administered at around the 48-hour interval from when it was first administered for TAP blocks, despite the manufacturer’s general guidance to wait 96 hours to administer any further local anesthetics after liposomal bupivacaine. This limb ischemia was obviously unforeseen when the TAP blocks with liposomal bupivacaine were performed at the time of laparotomy, and this morbid situation necessitated pragmatic thinking beyond usual dosing guidelines in order to accomplish a desired outcome. The patient and her family were informed before the procedure that there was a small risk for seizure or cardiac arrest, yet the risk was believed to be outweighed by the palliative benefit, given her terminal condition. This decision was not made lightly or without informing the patient and her family of the risk. The patient very clearly stated that she preferred to proceed with this method to pursue any reasonable chance at pain relief without being overly sedated with opioids. At 48 hours status post TAP block administration, a significant portion of the liposomal bupivacaine, and all of the bupivacaine with epinephrine, would have been metabolized, so the risk for an adverse event was believed to be acceptably low. As it turned out, this concern was indeed unfounded in this particular instance. Throughout and following the block placements, the patient was monitored vigilantly for signs of local anesthetic toxicity; although IV fat emulsion was kept available, it was not needed.

Had this not been a palliative procedure for the very short period of expected life remaining for this patient, local anesthetics would have been avoided for the full 96-hour abstinence recommendation that currently is in place. However, this case demonstrates at least one instance in which an accelerated administration of a second dose of a local anesthetic following liposomal bupivacaine was safely performed. This may merit further investigation into whether this 96-hour window is overly conservative and may be safely shortened in other instances.

Conclusion

Although the field of regional anesthesia has seen many changes over the years and its benefits have been extensively validated, an underexplored application remains in palliation of pain at the end of life. This case demonstrates an innovative use of two regional techniques, for which the extended pain relief provided by liposomal bupivacaine was of adequate duration to help the patient stay comfortable during 30 hours with an ischemic limb. Moreover, these regional blocks allowed for the patient to remain awake and coherent, allowing her to have a very meaningful visit with her family members before she drew her last breath. She was able to die with dignity and comfort, partially because of regional anesthetic techniques.