Preemptive Chlorepheniramine Maleate Reducing Postoperative Agitation
Condition: Agitated; State, Acute Reaction to Stress
MeSH terms: Psychomotor Agitation; Stress Disorders, Traumatic, Acute
Study type: Interventional

Summary: 
      The aim of the study is to identify the role of preoperative chlorepheniramine maleate on
      alleviating or reducing the severity of postoperative agitation following FESS procedures.
    

Detailed description: 
      A total of 90 adult patients undergoing FESS procedure for sinusitis with postoperative nasal
      packing. Written informed consent will be obtained from all patients before randomization.
      Patients will be divided equally into two groups the first 45 patients will be assigned to
      chlorepheniramine maleate group (A) and the other group to placebo group (B). Group
      assignment, preparation and administration of drugs will be performed by a junior anesthetist
      who is neither involved nor interested by any means in the study. Blind grouping will be kept
      to all including the patients themselves, until the completion of study.

      Inclusion and Exclusion Criteria The inclusion criteria of these patients include adult
      patients (age 18- 60 years), class I-II according to American society of anaesthesiologists
      (ASA) physical status subjected to FESS without septoplasty. Exclusion criteria include;
      patients below 18 years old or over 60 years old, patients with ASA physical status class
      III-IV, morbid obesity with BMI > 30 kgm-2 at initial hospital visit, history of
      neuro-psychatric ailment or chronic use of antipsychotic drugs, severe cardiovascular
      disease, any coagulopathies, pregnancy, history of relevant drug allergy, any possibility of
      anticipated difficult intubation.

      Preoperative Anesthetic Assessment All patients will be subjected to a thorough medical
      history, physical examination, laboratory investigations (fasting blood sugar, kidney, liver
      function tests, serum electrolytes, coagulation profile, and electrocardiogram)
      preoperatively. They will be also counseled about the anesthetic management and potential
      complications of both surgery and anesthesia, and the explanations of numerical pain analogue
      scale (NAS) from 0-10. All these data will be documented. A thorough airway assessment by
      Mallampati classification, mouth opening, neck movement, thyromental distance will be done to
      find out any possibility of difficult intubation. If there is a chance of significant
      difficult intubation, the patient will be excluded from the study.

      Anesthetic Protocol All patients admitted to OR induction area where patient identification
      is confirmed and an 18-gauge intravenous cannula will be inserted to all Participants.
      Participants of group A will receive only one ampoule of 45.5 mg/ 2mL chlorepheniramine
      maleate diluted in 8 ml isotonic saline intravenous (I.V) prior to induction of general
      anesthesia by 30 minutes while participants in group (B) will receive 10 ml isotonic saline
      (placebo) by the same route as control.

      General anesthesia will be started for all patients with intravenous lignocaine 1.0 mg/kg,
      propofol 2.0 mg/kg, then atracurium 0.5 mg/kg, fentanyl 1 µg/kg then they will be intubated
      orally which is fixed after confirmation of its place by auscultation then oral packing with
      wet gauze under vision using laryngoscope. Anesthesia will be maintained by mixture of O2 and
      air along with 2% sevoflurane then atracurium 0.1 mg/kg will be given for maintenance of
      muscle relaxation.. All patients will be monitored by standard monitors including, the pulse
      oximeter, non-invasive blood pressure, end-tidal C02, and electrocardiogram. Moreover,
      bispectral index monitor is used to assess depth of general anesthesia.

      Deliberate hypotension will be done using intravenous infusion of nitroglycerine at a rate of
      5 to 20 µg/ kg /minute titrated to target mean arterial blood pressure (Mbp) of 55±5 mmHg.
      Hypotensive anesthesia will be maintained throughout the surgical procedure. At the end of
      surgery, mean arterial blood pressure (Mbp) will be elevated by stoppage of nitroglycerine
      infusion and infusing crystalloids (500-1000ml) together with administration of ephedrine
      hydrochloride 10 mg IV to restore the mean arterial blood pressure back to the preoperative
      value. Upon attaining spontaneous breathing muscle relaxant will be antagonized by 50 µg/kg
      neostigmine and 10 µg/kg glycopyrolate, then oral pack will be removed under vision with
      thorough oral suctioning then awake extubation will be done and the patients will be
      transferred to the recovery unit.

      Postoperative Analgesic Regimen It will start immediately on arrival to the recovery unit
      where patients received 16 mg lornoxicam slowly IV over 5 minutes. After that all patients
      will receive acetaminophen 1 gm/6 h IV and 5 mg Nalbuphine IV if breakthrough pain develops
      for the first day postoperative.

      Patients Assessment Patients will be transferred to Post-anesthesia care unit PACU for
      observation and assessment for agitation and pain. Upon arrival to PACU, a pulse oximeter and
      Non invasive blood pressure (NIBP) monitors will be attached to the patient. Discharge
      criteria from PACU will be stable vital signs, pain score less than or equal to 2, no nausea
      or vomiting, calm and alert patient.

      Assessment of agitation Postoperative agitation will be assessed in the PACU by a blinded
      observer using the Richmond Agitation Sedation Scale (RASS) as follows: 0= Alert and calm +1=
      Restless; Anxious and /or apprehensive but movements not aggressive. +2= agitated; Frequent
      non-purposeful movement. +3= very agitated; Pulls on or removes the tubes or catheters or has
      aggressive behavior toward staff. +4= combative; overly combative or violent. Total agitation
      will be defined as the algebraic sum of agitation values will be observed at the measured
      time points (0, 5, 10, 15, 30 minutes after recovery), and this will be used to correlate
      agitation with other variables. The agitations score range will be from 0= no agitation to
      20= severe persistent agitation.

      In case of severe persistent agitation with RASS > 12 in the first 15 minutes postoperatively
      patients will be reassured and midazolam 2 mg IV will be given to reduce agitation with
      thorough follow up of patient's breathing.

      Assessment of pain Pain intensity will be assessed as a secondary outcome to the
      investigator's study using visual analogue scale where 0= no pain and 10 is the worst
      imaginable pain as rated by the patient. A blinded team member assessed pain after evaluation
      of last agitation point (30 minutes of recovery). Patient that exhibited no agitation will be
      also evaluated for pain after 30 minutes of recovery. Nalbuphine will be used as rescue
      analgesic to ameliorate pain. The use of nalbuphine after evaluation of agitation and
      assessment of pain to avoid perplex to the outcome measurement. If pain is more than +6 on
      VAS Nalbuphine will be given in 5 mg until pain score < 4. Pain assessment is done after 2, 6
      , 12 and 24 hours postoperatively with calculating the frequency of rescue analgesia given
      and the total dose of nalbuphine consumed during that time taking care not to exceed 5 Mg at
      a time with drug lag of at least 2 hours between 2 successive doses of rescue agent.

      The primary end point to this study is the occurance of severe agitation endangering the
      patient, or the occurance hypoxemia, bleeding nasal or oral, or the occurance of
      postoperative atypical hypotension.
    

Intervention name(s): Preemptive chlorepheniramine maleate intravenous injection; normal saline
Intervention type(s): Drug; Drug
Intervention description(s): Participants of group A will receive only one ampoule of 45.5 mg/ 2mL chlorepheniramine maleate diluted in 8 ml isotonic saline intravenous (I.V) prior to induction of general anesthesia by 30 minutes; participants in group (B) will receive 10 ml isotonic saline (placebo) by the same route as control.
Other intervention name(s): normal isotonic saline
Intervention MeSH terms: Maleic acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: chlorpheniramine maleate, Agitation, FESS