Effect of Dexmedetomidine on Stress Response and Emergence Agitation During Laparoscopic Surgery
Condition: Stress Response
MeSH terms: Psychomotor Agitation; Emergence Delirium
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      Emergence agitation is a post-anesthetic phenomenon that develops in the early phase of
      general anesthesia recovery, and is characterized by agitation, confusion, disorientation,
      and possible violent behavior. The incidence of emergence agitation is less common in adults
      as compared to pediatric patients. It may lead to serious consequences for the patient such
      as bleeding, falling, removal of catheters and self extubation, which lead to further
      complications like hypoxia and aspiration.

      Despite its common occurrence, unclear etiology, and serious sequelae, emergence agitation
      has rarely been studied in adults.

      The stress response to surgery is an unconscious response to tissue injury. Activation of the
      sympathetic nervous system, increase of catabolic hormone release and pituitary gland
      suppression are considered a response to surgical stress, in clinical practice these
      activities cause changes in heart rate, blood pressure and biochemical fluctuations of
      noradrenaline, adrenaline, dopamine, and cortisol. Above all, these fluctuations prolong
      hospitalization and delay patients discharge.

      Dexmedetomidine is a highly selective alpha-2 receptor agonist having sedative, analgesic and
      sympatholytic properties. Decreased stress response to surgery ensuring a stable hemodynamic
      state is a beneficial property of the agent. Peri-operative use of dexmedetomidine also
      decreases postoperative opioid consumption, pain intensity, and antiemetic therapy. However,
      the data related to the effects of dexmedetomidine on reducing agitation from general
      anesthesia in adults are limited.
    

Detailed description: 
      With no premedication, all patients will have pre-oxygenation for 3-5 minutes and intravenous
      access will be secured. NaCl 0.9% 4 ml/kg/h will be infused intraoperatively. General
      anesthesia will be induced by fentanyl 1 ug/kg, propofol 2 mg/kg and nimbex (cisatracurium)
      0.15 mg/kg. Endotracheal intubation then will be done using oral ETT of appropriate size
      under direct laryngoscopy and secured at the angle of the mouth. Sevoflurane inhalational
      anesthetic (2-4 %) and nimbex 0.03 mg/kg will be used for maintenance of anesthesia. The
      lungs will be mechanically ventilated to keep intra-operative EtCo2 between 35-40 mmHg.

      Intraoperative monitoring:

      Routine monitors including ECG, non-invasive blood pressure, pulse oxymetry and EtCo2 will be
      recorded every 5 minutes during the intra-operative 20 minutes of the study drug
      administration. Bradycadia (heart rate ˂ 60 beat/minute) will be treated with iv atropine 0.5
      mg. Hypotension (mean arterial blood pressure ˂ 60 mmHg) will be treated with iv ephedrine 5
      mg increments. Duration of anesthesia, sevoflurane % and duration of surgery will be
      recorded.

      At the end of surgery and stoppage of sevoflurane inhalation, neostigmine 0.04 mg/kg and
      atropine 0.02 mg/kg will be used for muscle relaxant reversal (Time 0 in the emergence
      process), patients will be extubated and transferred to the PACU for recovery and monitoring.

      Assessment in PACU:

      Routine monitoring will be continued during staying in PACU. During emergence, the level of
      agitation will be evaluated using the Ricker sedation-agitation scale (RSAS). The maximum
      level of agitation will be recorded for each patient at time 0, 5, 10, 20, 30, 60 and 120
      minutes. Emergence agitation was defined as any score on the sedation-agitation scale ≥ 5.
      Dangerous agitation was defined as a sedation-agitation scale score = 7 (3). If dangerous
      agitation occurs, it will be treated with fentanyl 1 ug/kg.

      Duration of stay in PACU will be recorded. Criteria for discharge from PACU will be applied
      according to the modified Aldrete scoring system. A score ≥ 9 was required for discharge.

      Postoperative Analgesia:

      The 10 points Visual Analogue Scale (VAS) for pain measurement will be used to assess the
      severity of postoperative pain. Score 0 indicates no pain and score 10 indicates severe pain.
      If VAS ≥ 4, rescue analgesia will be indicated. Perfalgan infusion will be used as
      supplemental analgesia. The first dose and the total amount in 24 hours of perfalgan will be
      recorded. Patient's satisfaction will be recorded at the end of the first 24 hours
      postoperatively.

      Blood Sampling:

      Venous blood samples will be collected from peripheral extremities away from the intravenous
      infused limb. Samples will be withdrawn 30 minutes pre-operatively, 30 minutes after skin
      incision, 2 and 24 hours after end of surgery. The blood samples will be centrifuged at 3500
      ×g for at least 10 minutes and then serum samples will be eluted. Blood glucose level will be
      also recorded at the same times.

      Statistical Analysis:

      Statistical analysis will be conducted with SPSS version 20 (SPSS Inc., Chicago, IL, USA) for
      Windows. The results will be expressed as mean ± SD, range, percentage. P-values < 0.05 will
      be considered statistically significant.
    

Intervention name(s): Dexmedetomidine
Intervention type(s): Drug
Intervention description(s): Group I will receive 1 ug/kg, group II will receive 0.75 ug/kg and group III will receive 0.5 ug/kg) diluted to 50 ml NaCl 0.9% by syringe pump over 20 minutes before end of surgery.
Intervention MeSH terms: Dexmedetomidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary purpose: Prevention
Keywords: Dexmedetomidine; Stress response; Emergence agitation