Analgesic Effect of IV Acetaminophen in Tonsillectomies

NCT01691690 | Completed Phase 2 Results

• 1 other identifier: IRB12-00097
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

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).

Conditions

Adenotonsillitis; Tonsillitis

Outcome Measures

Primary Outcomes (1)

• FLACC Pain Score Greater Than or Equal to 4

  The Face, Legs, Activity, Cry, Consolability scale or FLACC scale is a measurement used to assess pain for children between the ages of 2 months and 7 years or individuals that are unable to communicate their pain. The scale is scored in a range of 0-10 with 0 representing no pain. 5 pain measurements were performed at 0, 5, 15, 30, and 60 minutes after PACU arrival. This is the number of participants who reached a FLACC score \>/= 4 at one or more time points.

  0-60 mins post-operatively

Secondary Outcomes (2)

• Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each

  8-12 hours post-operatively

• Time of First Opioid Analgesia in PACU

  0-90 minutes post-operatively

Study Arms (2)

IV Acetaminophen

EXPERIMENTAL

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..

Drug: Acetaminophen (paracetamol); Drug: Midazolam; Drug: Sevoflurane; Drug: Nitrous Oxide/Oxygen; Drug: Propofol; Drug: Morphine; Drug: Ondansetron; Drug: Dexamethasone

Saline placebo infused intraoperatively

PLACEBO COMPARATOR

For this arm Morphine will be administered to manage pain.

Drug: Normal Saline Flush; Drug: Midazolam; Drug: Sevoflurane; Drug: Nitrous Oxide/Oxygen; Drug: Propofol; Drug: Morphine; Drug: Ondansetron; Drug: Dexamethasone

Interventions

Acetaminophen (paracetamol) DRUG

Acetaminophen IV (15 mg/kg).

IV Acetaminophen

Normal Saline Flush DRUG

Saline placebo will be infused intraoperatively.

Saline placebo infused intraoperatively

Midazolam DRUG

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

Also known as: Versed

IV Acetaminophen; Saline placebo infused intraoperatively

Sevoflurane DRUG

Sevoflurane for anesthesia induction.

IV Acetaminophen; Saline placebo infused intraoperatively

Nitrous Oxide/Oxygen DRUG

Combination of NO2 \& O2 for anesthesia induction.

IV Acetaminophen; Saline placebo infused intraoperatively

Propofol DRUG

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

IV Acetaminophen; Saline placebo infused intraoperatively

Morphine DRUG

Morphine 0.1 mg/kg given prior to intubation.

IV Acetaminophen; Saline placebo infused intraoperatively

Ondansetron DRUG

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

Also known as: Zofran

IV Acetaminophen; Saline placebo infused intraoperatively

Dexamethasone DRUG

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

IV Acetaminophen; Saline placebo infused intraoperatively

Eligibility Criteria

• Age: 2 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Male or female patients aged 2 years and younger than 9 years old requiring postoperative admission for tonsillectomy or adenotonsillectomy.
• Functional status as assigned by the American Society of Anesthesiology (ASA) classification of I (1), II (2) or III (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.
• Have parent/guardian who are compliant with routine medical care, capable of subjective evaluation and able to read, understand and sign the informed consent.

You may not qualify if:

• Male or female patients age greater than 9 years.
• Have an American Society of Anesthesiologists Physical Status \> IV (4)(severe disease that is life threatening).
• Have a known hypersensitivity or allergy to acetaminophen.
• Have a known allergy or intolerance to morphine or fentanyl.
• Have received chronic opioid analgesic therapy prior to surgery.
• Have renal disease.
• Have hepatic disease.
• Are morbidly obese (% BMI \> 95).

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related 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.

  PMID: 18811827 BACKGROUND

• 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.

  PMID: 21627768 BACKGROUND

• 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.

  PMID: 10443608 BACKGROUND

• 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.

  PMID: 19583073 BACKGROUND

• 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.

  PMID: 20693884 BACKGROUND

MeSH Terms

Conditions

Tonsillitis

Interventions

Acetaminophen; Midazolam; Sevoflurane; Nitrous Oxide; Oxygen; Propofol; Morphine; Ondansetron; Dexamethasone

Condition Hierarchy (Ancestors)

Pharyngitis; Respiratory Tract Infections; Infections; Pharyngeal Diseases; Stomatognathic Diseases; Respiratory Tract Diseases; Otorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Methyl Ethers; Ethers; Hydrocarbons, Fluorinated; Hydrocarbons, Halogenated; Hydrocarbons; Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds; Chalcogens; Elements; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Carbazoles; Indoles; Heterocyclic Compounds, 3-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Dr. Arlyne Thung
• Organization: Nationwide Children's Hospital

Arlyne.Thung@NationwideChildrens.org

(614) 722-4200

Study Officials

• Arlyne Thung, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: May 30, 2012
• First Posted: September 25, 2012
• Study Start: October 1, 2012
• Primary Completion: November 1, 2015
• Study Completion: July 1, 2016
• Last Updated: April 6, 2017
• Results First Posted: April 6, 2017

Record last verified: 2017-02

Locations

US (1)