Analgesic Effect of IV Acetaminophen in Tonsillectomies

Tonsillitis Clinical Trial

Official title:

Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01691690
• Other study ID #: IRB12-00097
• Status: Active, not recruiting
• Phase: Phase 2
• First received: May 30, 2012
• Last updated: May 10, 2016
• Start date: October 2012
• Est. completion date: May 2016

Study information

• Verified date: May 2016
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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 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).

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 240
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 9 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adenotonsillitis
• Tonsillitis

Intervention

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.
• Morphine (hydromorphone)
Saline placebo will be infused intraoperatively, and morphine (0.1 mg/kg) will be added to manage pain prior to intubation.

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Nationwide Children's Hospital

Country where clinical trial is conducted

United States, 

References & Publications (5)

Anderson BJ. Paracetamol (Acetaminophen): mechanisms of action. Paediatr Anaesth. 2008 Oct;18(10):915-21. doi: 10.1111/j.1460-9592.2008.02764.x. Review. — View Citation

Dashti GA, Amini S, Zanguee E. The prophylactic effect of rectal acetaminophen on postoperative pain and opioid requirements after adenotonsillectomy in children. Middle East J Anaesthesiol. 2009 Jun;20(2):245-9. — View Citation

Hong JY, Kim WO, Koo BN, Cho JS, Suk EH, Kil HK. Fentanyl-sparing effect of acetaminophen as a mixture of fentanyl in intravenous parent-/nurse-controlled analgesia after pediatric ureteroneocystostomy. Anesthesiology. 2010 Sep;113(3):672-7. doi: 10.1097/ALN.0b013e3181e2c34b. — View Citation

Korpela R, Korvenoja P, Meretoja OA. Morphine-sparing effect of acetaminophen in pediatric day-case surgery. Anesthesiology. 1999 Aug;91(2):442-7. — View Citation

Smith HS. Perioperative intravenous acetaminophen and NSAIDs. Pain Med. 2011 Jun;12(6):961-81. doi: 10.1111/j.1526-4637.2011.01141.x. Epub 2011 May 31. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		8-12 hours post-operatively	No
Secondary	To observe recovery characteristics in the PACU and floor in patients following tonsillectomy.		8-12 hours post-operatively	No