Analgesic Effect of IV Acetaminophen in Tonsillectomies
Condition: Adenotonsillitis; Tonsillitis
MeSH terms: Tonsillitis
Study type: Interventional
Phase: Phase 2

Summary: 
      Acetaminophen (paracetamol) is a first-line antipyretic and analgesic for mild and moderate
      pain for pediatric patients. Its common use (particularly in oral form) is underscored by its
      wide therapeutic window, safety profile, over the counter accessibility, lack of adverse
      systemic effects (as compared with NSAIDS and opioids) when given in appropriate doses.

      Although the exact anti-nociceptive mechanisms of acetaminophen continue to be elucidated,
      these mechanisms appear to be multi-factorial and include central inhibition of the
      cyclo-oxygenase (COX) enzyme leading to decreased production of prostaglandins from
      arachidonic acid, interference with serotonergic descending pain pathways, indirect
      activation of cannabinoid 1 (CB1) receptors and inhibition of nitric oxide pathways through
      N-methyl-D-aspartate (NMDA) or substance P. Of the above mechanisms, the most commonly known
      is that of central inhibition of COX enzymes by which the decreased production of
      prostaglandins diminish the release of excitatory transmitters of substance P and glutamate
      which are both involved in nociceptive transmission (Anderson, 2008; Smith, 2011).

      To date, several studies have shown acetaminophen's opioid sparing effect in the pediatric
      population when given by the rectal or intravenous routes (Korpela et al, 1999; Dashti et al,
      2009; Hong et al, 2010).
    

Detailed description: 
      Once enrolled, subjects will have a standardized anesthetic on the day of surgery:

        1. Pre-medication with oral midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20
           minutes before induction

        2. Inhalation induction with sevoflurane and a mixture of N20/02

        3. Propofol 1-1.5 mg/kg to facilitate endotracheal intubation

        4. Morphine 0.1 mg/kg given prior to intubation

        5. Maintenance anesthesia with isoflurane, titrated to 0.8-1 Minimal Anesthetic
           Concentration (MAC) with a mixture of Air/02

        6. Acetaminophen IV (15 mg/kg) vs. saline placebo infused intraoperatively (randomized by
           pharmacy)

        7. Ondansetron (0.15 mg/kg, maximum dose of 4 mg) and dexamethasone (0.25 mg/kg, maximum
           dose of 20 mg) for postoperative nausea prophylaxis.

      Following surgery and extubation, baseline vitals will be obtained and pain scores will be
      assessed in the post anesthesia care unit (PACU) via Faces, Legs, Activity, Cry,
      Consolability Scale (FLACC).The presence of emergence delirium will be assessed via Pediatric
      Agitation and Emergence Delirium scale (PAED). Those subjects whose pain score is assessed at
      < 4 will receive standard postoperative care and no analgesics. Assessed pain scores > 4 will
      receive 0.5mcg/kg fentanyl q10 minutes as needed. Variables such as time to extubation in the
      PACU, time to first analgesic delivery, pain scores, # times/total dose of opioids given,
      presence of sedation, nausea/vomiting, duration of oxygen requirement in PACU, whether or not
      patient was discharged to floor on oxygen and total PACU time will be recorded during the
      duration of the patient's PACU stay. Subjects will be discharged to the inpatient floor from
      the PACU once standard discharge criteria have been met.

      Following discharge from the PACU, standardized analgesics will be given for breakthrough
      pain (oral oxycodone 0.1mg/kg q4hrs pro re nata (PRN) pain). Enrolled patients will be
      followed during the duration of their inpatient stay. Duration of oxygen requirement on the
      floor, pain scores and number of administered oxycodone doses on the floor will be monitored
      and recorded.
    

Intervention name(s): Acetaminophen (paracetamol); Normal Saline Flush; Midazolam; Sevoflurane; Nitrous Oxide/Oxygen; Propofol; Morphine; Ondansetron; Dexamethasone
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Acetaminophen IV (15 mg/kg).; Saline placebo will be infused intraoperatively.; Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.; Sevoflurane for anesthesia induction.; Combination of NO2 & O2 for anesthesia induction.; Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.; Morphine 0.1 mg/kg given prior to intubation.; Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.; Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.
Other intervention name(s): Versed; Zofran
Intervention MeSH terms: Acetaminophen; Dexamethasone; Midazolam; Morphine; Nitrous Oxide; Ondansetron; Propofol; Sevoflurane
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment