Analgesic Effect of IV Acetaminophen in Tonsillectomies
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| ClinicalTrials.gov Identifier: NCT01691690 |
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Recruitment Status :
Completed
First Posted : September 25, 2012
Results First Posted : April 6, 2017
Last Update Posted : April 6, 2017
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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 or disease | Intervention/treatment | 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 |
Once enrolled, subjects will have a standardized anesthetic on the day of surgery:
- Pre-medication with oral midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction
- Inhalation induction with sevoflurane and a mixture of N20/02
- Propofol 1-1.5 mg/kg to facilitate endotracheal intubation
- Morphine 0.1 mg/kg given prior to intubation
- Maintenance anesthesia with isoflurane, titrated to 0.8-1 Minimal Anesthetic Concentration (MAC) with a mixture of Air/02
- Acetaminophen IV (15 mg/kg) vs. saline placebo infused intraoperatively (randomized by pharmacy)
- 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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 250 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Analgesic Effect of Single Dose Intravenous Acetaminophen in Pediatric Patients Undergoing Tonsillectomy |
| Study Start Date : | October 2012 |
| Actual Primary Completion Date : | November 2015 |
| Actual Study Completion Date : | July 2016 |
| Arm | Intervention/treatment |
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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..
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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. |
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Placebo Comparator: Saline placebo infused intraoperatively
For this arm Morphine will be administered to manage pain.
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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. |
- 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.
- 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.
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| Ages Eligible for Study: | 2 Years to 9 Years (Child) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01691690
| United States, Ohio | |
| Nationwide Children's Hospital | |
| Columbus, Ohio, United States, 43205 | |
| Principal Investigator: | Arlyne Thung, MD | Nationwide Children's Hospital |
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 |
| First Posted: | September 25, 2012 Key Record Dates |
| Results First Posted: | April 6, 2017 |
| Last Update Posted: | April 6, 2017 |
| Last Verified: | February 2017 |
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Tonsillitis Pharyngitis Pharyngeal Diseases Stomatognathic Diseases Respiratory Tract Infections Respiratory Tract Diseases Otorhinolaryngologic Diseases Acetaminophen Dexamethasone Midazolam Morphine Nitrous Oxide Ondansetron Propofol Sevoflurane |
Analgesics 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 Molecular Mechanisms of Pharmacological Action Hypnotics and Sedatives Central Nervous System Depressants |