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Analgesic Effect of IV Acetaminophen in Tonsillectomies

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT01691690
Enrollment
250
Registered
2012-09-25
Start date
2012-10-31
Completion date
2016-07-31
Last updated
2017-04-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Adenotonsillitis, Tonsillitis

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.

Interventions

Acetaminophen IV (15 mg/kg).

Saline placebo will be infused intraoperatively.

DRUGMidazolam

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

DRUGSevoflurane

Sevoflurane for anesthesia induction.

DRUGNitrous Oxide/Oxygen

Combination of NO2 & O2 for anesthesia induction.

DRUGPropofol

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

DRUGMorphine

Morphine 0.1 mg/kg given prior to intubation.

DRUGOndansetron

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

DRUGDexamethasone

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

Sponsors

Nationwide Children's Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender
ALL
Age
2 Years to 9 Years
Healthy volunteers
No

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).

Design outcomes

Primary

MeasureTime frameDescription
FLACC Pain Score Greater Than or Equal to 40-60 mins post-operativelyThe 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

MeasureTime frameDescription
Time of First Opioid Analgesia in PACU0-90 minutes post-operativelyMean time to first drug administration among patients requiring opioid analgesia in the PACU.
Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each8-12 hours post-operativelyAnalgesics administered after arrival to the inpatient ward included hydrocodone/acetaminophen, oxycodone, NSAIDS, acetaminophen, and morphine.

Countries

United States

Participant flow

Participants by arm

ArmCount
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. Acetaminophen (paracetamol): Acetaminophen IV (15 mg/kg) will be infused intraoperatively over 15 minutes to evaluate the opioid-sparing effect and pain score reduction in pediatric patients undergoing tonsillectomy or adenotonsillectomy procedures. Morphine (hydromorphone): Morphine (0.1 mg/kg) will be added to manage pain prior to intubation.
118
Saline Placebo
Patients will receive pre-medication with oral midazolam. Participants of this control arm will receive saline to establish a control model for evaluating opioid-sparing effect and pain score reduction compared to the intervention arm. Sodium Chloride (saline): 0.9% Sodium Chloride Placebo will be infused intraoperatively over 15 minutes to establish a control model while evaluating the pain score differences in pediatric patients undergoing tonsillectomy or adenotonsillectomy procedures. Morphine (hydromorphone): Morphine (0.1 mg/kg) will be added to manage pain prior to intubation.
121
Total239

Baseline characteristics

CharacteristicSaline PlaceboIV AcetaminophenTotal
Age, Continuous4.84 years
STANDARD_DEVIATION 1.42
4.87 years
STANDARD_DEVIATION 1.53
4.855 years
STANDARD_DEVIATION 1.476
Body Mass Index (kg/m2)15.29 Kg/m2
STANDARD_DEVIATION 1.36
15.56 Kg/m2
STANDARD_DEVIATION 1.58
15.42 Kg/m2
STANDARD_DEVIATION 1.47
Extubation time (min)15.38 minutes
STANDARD_DEVIATION 8.52
16.65 minutes
STANDARD_DEVIATION 7.68
16.01 minutes
STANDARD_DEVIATION 8.12
Height (cm)108.78 centimeters
STANDARD_DEVIATION 10.37
109.31 centimeters
STANDARD_DEVIATION 10.82
109.04 centimeters
STANDARD_DEVIATION 10.58
Post-Anesthetic Care Unit time (min)65.07 minutes
STANDARD_DEVIATION 19.4
64.57 minutes
STANDARD_DEVIATION 23.41
64.82 minutes
STANDARD_DEVIATION 21.44
Procedure time (min)16.65 minutes
STANDARD_DEVIATION 5.9
15.85 minutes
STANDARD_DEVIATION 5.78
16.26 minutes
STANDARD_DEVIATION 5.85
Sex: Female, Male
Female
59 Participants62 Participants121 Participants
Sex: Female, Male
Male
62 Participants56 Participants118 Participants
Time to first analgesic on unit (min)297.09 minutes
STANDARD_DEVIATION 106.91
298.36 minutes
STANDARD_DEVIATION 97.52
297.74 minutes
STANDARD_DEVIATION 101.97
Weight (kg)18.27 kilograms
STANDARD_DEVIATION 4.02
18.85 kilograms
STANDARD_DEVIATION 4.74
18.56 kilograms
STANDARD_DEVIATION 4.39

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
11 / 11816 / 121
serious
Total, serious adverse events
0 / 1180 / 121

Outcome results

Primary

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.

Time frame: 0-60 mins post-operatively

ArmMeasureValue (COUNT_OF_PARTICIPANTS)
IV AcetaminophenFLACC Pain Score Greater Than or Equal to 458 Participants
Saline PlaceboFLACC Pain Score Greater Than or Equal to 469 Participants
Secondary

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

Analgesics administered after arrival to the inpatient ward included hydrocodone/acetaminophen, oxycodone, NSAIDS, acetaminophen, and morphine.

Time frame: 8-12 hours post-operatively

Population: Comparing both groups for the time study subjects required breakthrough pain medication on the ward.

ArmMeasureGroupValue (COUNT_OF_PARTICIPANTS)
IV AcetaminophenAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachhydrocodone/acetaminophen68 Participants
IV AcetaminophenAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachacetaminophen3 Participants
IV AcetaminophenAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachoxycodone31 Participants
IV AcetaminophenAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachmorphine1 Participants
IV AcetaminophenAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring EachNSAIDS15 Participants
Saline PlaceboAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachmorphine0 Participants
Saline PlaceboAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring EachNSAIDS22 Participants
Saline PlaceboAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachhydrocodone/acetaminophen57 Participants
Saline PlaceboAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachoxycodone39 Participants
Saline PlaceboAnalgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Eachacetaminophen2 Participants
Secondary

Time of First Opioid Analgesia in PACU

Mean time to first drug administration among patients requiring opioid analgesia in the PACU.

Time frame: 0-90 minutes post-operatively

ArmMeasureValue (MEAN)Dispersion
IV AcetaminophenTime of First Opioid Analgesia in PACU56.80 minutesStandard Deviation 14.15
Saline PlaceboTime of First Opioid Analgesia in PACU60.46 minutesStandard Deviation 20.51

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026