Labetalol and Esmolol: Vital Signs and Post Operative Pain Management
Condition: Laparoscopic Surgery
Study type: Interventional
Phase: Phase 4

Summary: 
      This study proposes to investigate the effects of labetalol or esmolol on managing the vital
      signs (like blood pressure and heart rate) during surgery, on pain management, and on the
      later recovery after surgery.

      It will also assess the cost-effectiveness of Labetalol and esmolol for outpatient surgery.
    

Detailed description: 
      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.
    

Intervention name(s): Fentanyl; Labetalol; Esmolol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Fentanyl 50 micrograms/ml boluses will be given:
at the induction time
at the time before surgical incision, and
as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm); Labetalol 5 mg/ml boluses will be given:
at the induction time
at the time before surgical incision, and
as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm); Esmolol 10 mg/ml boluses will be given:
at the induction time
at the time before surgical incision, and
as needed to maintain hemodynamic stability during the intraoperative period (MAP within 15% of the pre-induction baseline value, and/or HR > 80 bpm)
Other intervention name(s): Brevibloc
Intervention MeSH terms: Labetalol; Fentanyl; Esmolol
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: Labetalol; Esmolol; Fentanyl; Anesthetic adjuvant; Ambulatory surgery; Outpatient surgery; Pain management; Hemodynamic stability; Perioperative outcomes