Effect of Lidocaine and Esmolol to Improve the Quality of Recovery

Finding the optimal combination of anesthetic adjuvant drugs for maintaining hemodynamic
stability during surgery is a challenge (1-3). Traditionally, potent opioid analgesics like
fentanyl and its newer analogs have been used for this purpose. However, use of opioid
compounds is associated with well-known side effects (e.g., ventilatory depression,
postoperative nausea and vomiting, constipation, ileus, bladder dysfunction, urinary
retention, pruritus, drowsiness and sedation). All of these common side effects interfere
with the early recovery process and contribute to a delayed resumption of normal activities
(4, 5). Increasingly, non-opioid analgesics (e.g. β-blockers and local anesthetics) are
being utilized as adjuvant drugs during surgery for treatment of acute hyperdynamic
responses (increased catecholamine release) during surgery, as well as, facilitation of the
recovery process after surgery because of their anesthetic and analgesic-sparing effects.
The β-blocking drugs, esmolol and labetalol have been used as an alternative to short-acting
opioid analgesics for controlling the transient, acute autonomic responses during surgery
(5-8), They have been shown to reduce the anesthetic requirement during intravenous
(propofol) or volatile-based anesthesia (6,7,10-13) and to decrease opioid consumption
intraoperatively and in the PACU (8). They may also improve hemodynamic stability during
induction and emergence from anesthesia in the perioperative and early postoperative period
and facilitate the resumption of normal activities after major surgical procedures. The
anesthetic and analgesic-sparing effects of β -blockers also lead to a faster emergence from
anesthesia and reduce postoperative opioid side effects (e.g., PONV) (14-18). Perioperative
intravenous esmolol has shown improvement in perioperative outcomes, decreases acute
hemodynamic responses, reduces anesthetics and opioids use during anesthesia, facilitates a
faster emergence from anesthesia, reduces intraoperative and postoperative opioid
requirements, reduces side effects as such as pruritus, constipation, ileus, nausea and
vomiting (PONV) and thereby shortens the hospital stay. (3, 7, 13, 18)

Local anesthetics like lidocaine possess analgesic, antihyperalgesic and anti-inflammatory
properties. Perioperative intravenous lidocaine has shown improvement in perioperative
outcomes in patients undergoing abdominal surgery to decrease intraoperative requirement of
Inhalants/Intravenous agents, opioid consumption, postoperative pain, fatigue, nausea and
vomiting scores, maintain hemodynamic stability, facilitate a more rapid recovery of
gastrointestinal function, improve postoperative recovery, fast resumption of normal
activities of daily living and shorten length of hospital stay, when administered as an
adjuvant during surgery.(19,23-29,33)

Theoretically, it would be extremely beneficial to administer an adjuvant (to patients
undergoing abdominal surgery) that is capable of effectively controlling autonomic responses
during surgery, while providing a faster recovery with fewer side effects. Preliminary data
suggests that the perioperative effects of systemic administration of lidocaine and esmolol
is most effective in facilitating bowel recovery, decreasing opioid consumption in the
intra/postoperative period, and shorten length of hospital stay with early recovery.
Therefore, we designed this prospective, randomized, double-blinded, active-controlled study
to test the hypothesis that systemic administration of lidocaine and esmolol in combination
(vs. either drug alone) for maintenance of hemodynamic stability during surgery will result
in improved postoperative outcomes for patients undergoing abdominal surgery (e.g., less
pain and postoperative nausea and vomiting, and faster return of bowel function and
resumption of normal activities of daily living); leading to a shorten length of hospital
stay.

Inclusion Criteria:

- Patients scheduled to undergo abdominal surgical procedures

- Willingness and ability to sign an informed consent document

- No allergies to anesthetic or analgesic medications

- 18 - 80 years of age

- American Society of Anesthesiologists (ASA) physical status classification: Class I -
III adults of either sex

- Women of childbearing potential must be currently practicing an acceptable form of
birth control, and have a negative urine or blood pregnancy test

- Patients with systolic blood pressure greater than 80 and less than 150 at baseline,
diastolic blood pressure less than 100 at baseline.

Exclusion Criteria:

- Inability to comprehend the pain assessment tools.

- Patients with known allergy, hypersensitivity or contraindications to anesthetic or
analgesic medications

- Patients with clinically-significant medical conditions, such as brain, heart,
kidney, endocrine, or liver diseases,

- Peptic ulcer disease or bleeding disorders

- Patients with history of hepatic, renal, cardiac failure, organ transplant, or
diabetes

- Patients with reactive airway disease (asthma)

- Patients with seizures

- Chronic use of ß-blocker or calcium channel blocker

- Morbid obesity (body mass index >40)

- Pregnant or lactating women

- Subjects with a history of alcohol or drug abuse within the past 3 months

- Any other conditions or use of any medication which may interfere with the conduct of
the study