Analgesic Effect of IV Acetaminophen in Tonsillectomies
Condition: Adenotonsillitis; Tonsillitis
MeSH terms: Tonsillitis
Intervention: Acetaminophen (paracetamol); Normal Saline Flush; Midazolam; Sevoflurane; Nitrous Oxide/Oxygen; Propofol; Morphine; Ondansetron; Dexamethasone
Intervention description: 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.
Intervention MeSH terms: Acetaminophen; Dexamethasone; Midazolam; Morphine; Nitrous Oxide; Ondansetron; Propofol; Sevoflurane
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 250.0
Sex: All
Minimum age: 2 Years
Maximum age: 9 Years
Healthy volunteers: No

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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female patients aged 2 years and younger than 9 years old requiring
             postoperative admission for tonsillectomy or adenotonsillectomy.

          2. Functional status as assigned by the American Society of Anesthesiology (ASA)
             classification of I (1), II (2) or III (3).

          3. Have a parent/guardian who are able to provide written informed consent in accordance
             with Human Investigations Committee/Institutional Review Board (HIC/IRB) regulations.

          4. Have parent/guardian who are compliant with routine medical care, capable of
             subjective evaluation and able to read, understand and sign the informed consent.

        Exclusion Criteria:

          1. Male or female patients age greater than 9 years.

          2. Have an American Society of Anesthesiologists Physical Status > IV (4)(severe disease
             that is life threatening).

          3. Have a known hypersensitivity or allergy to acetaminophen.

          4. Have a known allergy or intolerance to morphine or fentanyl.

          5. Have received chronic opioid analgesic therapy prior to surgery.

          6. Have renal disease.

          7. Have hepatic disease.

          8. Are morbidly obese (% BMI > 95).