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Analgesic Effect of IV Acetaminophen in Tonsillectomies

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Arlyne Thung, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT01691690
First received: May 30, 2012
Last updated: February 21, 2017
Last verified: February 2017
  Purpose

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).


Condition Intervention Phase
Adenotonsillitis
Tonsillitis
Drug: Acetaminophen (paracetamol)
Drug: Normal Saline Flush
Drug: Midazolam
Drug: Sevoflurane
Drug: Nitrous Oxide/Oxygen
Drug: Propofol
Drug: Morphine
Drug: Ondansetron
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
Official Title: Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy

Resource links provided by NLM:


Further study details as provided by Arlyne Thung, Nationwide Children's Hospital:

Primary Outcome Measures:
  • FLACC Pain Score Greater Than or Equal to 4 [ Time Frame: 0-60 mins post-operatively ]
    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.


Secondary Outcome Measures:
  • Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each [ Time Frame: 8-12 hours post-operatively ]
    Analgesics administered after arrival to the inpatient ward included hydrocodone/acetaminophen, oxycodone, NSAIDS, acetaminophen, and morphine.

  • Time of First Opioid Analgesia in PACU [ Time Frame: 0-90 minutes post-operatively ]
    Mean time to first drug administration among patients requiring opioid analgesia in the PACU.


Enrollment: 250
Study Start Date: October 2012
Study Completion Date: July 2016
Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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..
Drug: Acetaminophen (paracetamol)
Acetaminophen IV (15 mg/kg).
Drug: Midazolam
Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.
Other Name: Versed
Drug: Sevoflurane
Sevoflurane for anesthesia induction.
Drug: Nitrous Oxide/Oxygen
Combination of NO2 & O2 for anesthesia induction.
Drug: Propofol
Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.
Drug: Morphine
Morphine 0.1 mg/kg given prior to intubation.
Drug: Ondansetron
Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.
Other Name: Zofran
Drug: Dexamethasone
Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.
Placebo Comparator: Saline placebo infused intraoperatively
For this arm Morphine will be administered to manage pain.
Drug: Normal Saline Flush
Saline placebo will be infused intraoperatively.
Drug: Midazolam
Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.
Other Name: Versed
Drug: Sevoflurane
Sevoflurane for anesthesia induction.
Drug: Nitrous Oxide/Oxygen
Combination of NO2 & O2 for anesthesia induction.
Drug: Propofol
Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.
Drug: Morphine
Morphine 0.1 mg/kg given prior to intubation.
Drug: Ondansetron
Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.
Other Name: Zofran
Drug: Dexamethasone
Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.

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.

  Eligibility

Ages Eligible for Study:   2 Years to 9 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01691690

Locations
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Nationwide Children's Hospital
Investigators
Principal Investigator: Arlyne Thung, MD Nationwide Children's Hospital
  More Information

Publications:
Responsible Party: Arlyne Thung, Clinical Assistant Professor, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT01691690     History of Changes
Other Study ID Numbers: IRB12-00097
Study First Received: May 30, 2012
Results First Received: September 7, 2016
Last Updated: February 21, 2017

Additional relevant MeSH terms:
Tonsillitis
Pharyngitis
Pharyngeal Diseases
Stomatognathic Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Otorhinolaryngologic Diseases
Dexamethasone acetate
Dexamethasone
Ondansetron
Dexamethasone 21-phosphate
BB 1101
Morphine
Acetaminophen
Nitrous Oxide
Analgesics
Propofol
Midazolam
Sevoflurane
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on May 25, 2017