This trial is active, not recruiting.

Conditions adenotonsillitis, tonsillitis
Treatments acetaminophen (paracetamol), morphine (hydromorphone)
Phase phase 2
Sponsor Nationwide Children's Hospital
Start date October 2012
End date May 2016
Trial size 240 participants
Trial identifier NCT01691690, IRB12-00097


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 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).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose treatment
Patients will receive pre-medication with oral midazolam Participants of this experimental arm of the study will receive Acetaminophen IV to evaluate opioid-sparing effect and pain score reduction..
acetaminophen (paracetamol)
Acetaminophen IV (15 mg/kg) administered to evaluate the opioid-sparing effect and pain score reduction in pediatric patients undergoing tonsillectomy or adenotonsillectomy procedures. In addition, Morphine will be used in this arm to manage pain as in the placebo arm of the study.
(Placebo Comparator)
For this arm Morphine will be administered to manage pain.
morphine (hydromorphone)
Saline placebo will be infused intraoperatively, and morphine (0.1 mg/kg) will be added to manage pain prior to intubation.

Primary Outcomes

Analgesic efficacy of single dose intravenous acetaminophen in pediatric patients undergoing tonsillectomy to measure opioid consumption and pain scores in the first 8-12 postoperative hours.
time frame: 8-12 hours post-operatively

Secondary Outcomes

To observe recovery characteristics in the PACU and floor in patients following tonsillectomy.
time frame: 8-12 hours post-operatively

Eligibility Criteria

Male or female participants from 2 years up to 9 years old.

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 HIC 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).

Additional Information

Official title Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy
Principal investigator Arlyne Thung, MD
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 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 FLACC (Faces, Legs, Activity, Cry, Consolability Scale).The presence of emergence delirium will be assessed via PAED (Pediatric Agitation and Emergence Delirium scale). 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 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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2016.
Information provided to ClinicalTrials.gov by Nationwide Children's Hospital.