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Analgesic Effect of IV Acetaminophen in Tonsillectomies

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Nationwide Children's Hospital
Sponsor:
Information provided by (Responsible Party):
Arlyne Thung, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT01691690
First received: May 30, 2012
Last updated: July 17, 2014
Last verified: July 2014

May 30, 2012
July 17, 2014
October 2012
October 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Analgesic efficacy of single dose intravenous acetaminophen in pediatric patients undergoing tonsillectomy by means of opioid consumption and pain scores in the first 8-12 postoperative hours. [ Time Frame: 8-12 hours post-operatively ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01691690 on ClinicalTrials.gov Archive Site
To observe recovery characteristics in the PACU and floor in patients following tonsillectomy. [ Time Frame: 8-12 hours post-operatively ] [ Designated as safety issue: No ]
Recovery characteristics in the PACU and floor in patients following tonsillectomy. [ Time Frame: 8-12 hours post-operatively ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Analgesic Effect of IV Acetaminophen in Tonsillectomies
Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy

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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
  • Adenotonsillitis
  • Tonsillitis
  • Drug: 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.
  • Drug: Morphine (hydromorphone)
    Saline placebo will be infused intraoperatively, and morphine (0.1 mg/kg) will be added to manage pain prior to intubation.
  • Experimental: IV Acetaminophen
    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..
    Intervention: Drug: Acetaminophen (paracetamol)
  • Placebo Comparator: Saline placebo infused intraoperatively
    For this arm Morphine will be administered to manage pain.
    Intervention: Drug: Morphine (hydromorphone)

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
240
December 2014
October 2014   (final data collection date for primary outcome measure)

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).
Both
2 Years to 9 Years
No
United States
 
NCT01691690
IRB12-00097
No
Arlyne Thung, Nationwide Children's Hospital
Nationwide Children's Hospital
Not Provided
Principal Investigator: Arlyne Thung, MD Nationwide Children's Hospital
Nationwide Children's Hospital
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP