Adenotonsillitis, Tonsillitis
Conditions
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.
Midazolam (0.5mg/kg to maximum dose of 20mg) given 15-20 minutes before induction.
Sevoflurane for anesthesia induction.
Combination of NO2 & O2 for anesthesia induction.
Propofol 1-1.5 mg/kg to facilitate endotracheal intubation.
Morphine 0.1 mg/kg given prior to intubation.
Ondansetron (0.15 mg/kg, maximum dose of 4 mg) for postoperative nausea prophylaxis.
Dexamethasone (0.25 mg/kg, maximum dose of 20 mg) for postoperative nausea prophylaxis.
Sponsors
Study design
Eligibility
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
| Measure | Time frame | Description |
|---|---|---|
| FLACC Pain Score Greater Than or Equal to 4 | 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
| Measure | Time frame | Description |
|---|---|---|
| Time of First Opioid Analgesia in PACU | 0-90 minutes post-operatively | Mean 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 Each | 8-12 hours post-operatively | Analgesics administered after arrival to the inpatient ward included hydrocodone/acetaminophen, oxycodone, NSAIDS, acetaminophen, and morphine. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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 |
| Total | 239 |
Baseline characteristics
| Characteristic | Saline Placebo | IV Acetaminophen | Total |
|---|---|---|---|
| Age, Continuous | 4.84 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 Participants | 62 Participants | 121 Participants |
| Sex: Female, Male Male | 62 Participants | 56 Participants | 118 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 type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 11 / 118 | 16 / 121 |
| serious Total, serious adverse events | 0 / 118 | 0 / 121 |
Outcome results
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| IV Acetaminophen | FLACC Pain Score Greater Than or Equal to 4 | 58 Participants |
| Saline Placebo | FLACC Pain Score Greater Than or Equal to 4 | 69 Participants |
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.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| IV Acetaminophen | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | hydrocodone/acetaminophen | 68 Participants |
| IV Acetaminophen | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | acetaminophen | 3 Participants |
| IV Acetaminophen | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | oxycodone | 31 Participants |
| IV Acetaminophen | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | morphine | 1 Participants |
| IV Acetaminophen | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | NSAIDS | 15 Participants |
| Saline Placebo | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | morphine | 0 Participants |
| Saline Placebo | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | NSAIDS | 22 Participants |
| Saline Placebo | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | hydrocodone/acetaminophen | 57 Participants |
| Saline Placebo | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | oxycodone | 39 Participants |
| Saline Placebo | Analgesics Administered After Arrival to Inpatient Ward and Number of Participants Requiring Each | acetaminophen | 2 Participants |
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IV Acetaminophen | Time of First Opioid Analgesia in PACU | 56.80 minutes | Standard Deviation 14.15 |
| Saline Placebo | Time of First Opioid Analgesia in PACU | 60.46 minutes | Standard Deviation 20.51 |