Analgesic Effect of IV Acetaminophen in Tonsillectomies

NCT ID: NCT01691690

Last Updated: 2017-04-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2016-07-31

Brief 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.

Conditions

Adenotonsillitis; Tonsillitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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..

Group Type: EXPERIMENTAL

Acetaminophen (paracetamol)

Intervention Type: DRUG

Acetaminophen IV (15 mg/kg).

Midazolam

Intervention Type: DRUG

Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.

Sevoflurane

Intervention Type: DRUG

Sevoflurane for anesthesia induction.

Nitrous Oxide/Oxygen

Intervention Type: DRUG

Combination of NO2 \& O2 for anesthesia induction.

Propofol

Intervention Type: DRUG

Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.

Morphine

Intervention Type: DRUG

Morphine 0.1 mg/kg given prior to intubation.

Ondansetron

Intervention Type: DRUG

Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.

Dexamethasone

Intervention Type: DRUG

Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.

Saline placebo infused intraoperatively

For this arm Morphine will be administered to manage pain.

Group Type: PLACEBO_COMPARATOR

Normal Saline Flush

Intervention Type: DRUG

Saline placebo will be infused intraoperatively.

Midazolam

Intervention Type: DRUG

Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.

Sevoflurane

Intervention Type: DRUG

Sevoflurane for anesthesia induction.

Nitrous Oxide/Oxygen

Intervention Type: DRUG

Combination of NO2 \& O2 for anesthesia induction.

Propofol

Intervention Type: DRUG

Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.

Morphine

Intervention Type: DRUG

Morphine 0.1 mg/kg given prior to intubation.

Ondansetron

Intervention Type: DRUG

Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.

Dexamethasone

Intervention Type: DRUG

Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.

Interventions

Acetaminophen (paracetamol)

Acetaminophen IV (15 mg/kg).

Intervention Type: DRUG

Normal Saline Flush

Saline placebo will be infused intraoperatively.

Intervention Type: DRUG

Midazolam

Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.

Intervention Type: DRUG

Sevoflurane

Sevoflurane for anesthesia induction.

Intervention Type: DRUG

Nitrous Oxide/Oxygen

Combination of NO2 \& O2 for anesthesia induction.

Intervention Type: DRUG

Propofol

Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.

Intervention Type: DRUG

Morphine

Morphine 0.1 mg/kg given prior to intubation.

Intervention Type: DRUG

Ondansetron

Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.

Intervention Type: DRUG

Dexamethasone

Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.

Intervention Type: DRUG

Other Intervention Names

Versed; Zofran

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).

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 9 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nationwide Children's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Arlyne Thung

Clinical Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Arlyne Thung, MD

Role: PRINCIPAL_INVESTIGATOR

Nationwide Children's Hospital

Locations

Nationwide Children's Hospital

Columbus, Ohio, United States

Countries

United States

References

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

Reference Type: BACKGROUND

PMID: 18811827 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21627768 (View on PubMed)

Korpela R, Korvenoja P, Meretoja OA. Morphine-sparing effect of acetaminophen in pediatric day-case surgery. Anesthesiology. 1999 Aug;91(2):442-7. doi: 10.1097/00000542-199908000-00019.

Reference Type: BACKGROUND

PMID: 10443608 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19583073 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20693884 (View on PubMed)

Other Identifiers

IRB12-00097

Identifier Type: -

Identifier Source: org_study_id