Investigating Analgesic Efficacy of Intravenous Acetaminophen in Pediatric Tonsillectomy

Randomized Prospective Study Randomized Prospective Study Investigating the Analgesic Efficacy of Investigating the Analgesic Efficacy of Intravenous Acetaminophen Intravenous Acetaminophen in Reducing Post in Reducing Post- -Tonsillectomy Pain Tonsillectomy Pain in Pediatric Patients in Pediatric Patients Principal Investigator: Judy Audas CRNA, DNAP, MSN 1

To investigate the analgesic efficacy of intravenous acetaminophen for pediatric patients undergoing tonsillectomy on an outpatient basis. Purpose of Study 2

Cost-effectiveness of intravenous acetaminophen for pediatric tonsillectomySubramanyam R1, Varughese A, Kurth CD, Eckman MH. OBJECTIVE: The primary outcome of this study was to examine the cost-effectiveness of the intraoperative combination of intravenous (IV) acetaminophen and IV opioids, versus IV opioids alone, as a part of an inhalational anesthetic technique for tonsillectomy in children. METHODS: We studied the use of rescue analgesics in the postanesthesia care unit (PACU), adverse effects of acetaminophen and opioids, and costs associated with adverse effects. RESULTS: In the base case, IV acetaminophen in combination with opioids was both less costly ($17.12) and more effective (3.3% fewer rescue events) CONCLUSIONS: The routine use of IV acetaminophen as an adjuvant to IV opioids for tonsillectomy with or without adenoidectomy in children aged <17 years should be considered as a means to reduce the need for rescue analgesia and in turn reduce costs. Paediatr Anaesth. 2014 May;24(5):467-75. doi: 10.1111/pan.12359. Epub 2014 Mar 5. Literature Review 3

Arlyne Thung MD, Nationwide Childrens Hospital Started 10/2012; expected completion 12/2014 240 subjects needed; ages 2-8 ASA I-III scheduled for overnight admission Protocol: 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 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. FLACC scores, PAED scores, time to 1st analgesic given, & total doses of analgesic given are recorded Concurrent Pediatric IV Acetaminophen Study 4

Tylenol-po 5mL cup - $1 (160 mg) 1 tab (325mg) - $0.06 (that's right- 6 cents) Tylenol-IV 1 bottle - $211.42 (That s right, IV Tylenol is 3523.666667 x more costly than a tablet of Tylenol). Cost to Patients at CCHMC (per Brenda Parsons Pharmacy) 5

Randomized, prospective, double blind, placebo study Computer generated randomization scheme controlled by pharmacy Specific anesthetic management is at the discretion of the anesthesia team (except related to opioid dosing) Study Design 6

CCHMC Main and Liberty campuses Daily OR schedule Review of medical record for inclusion or exclusion criteria Invitation in with phone call the week before surgery with explanation of study purpose Detailed explanation of study & consent completed by parent on day of surgery (assent by patient if applicable) Methods/Recruitment 7

Age 3 to 10 years Weighs more than 10.0 kg Scheduled for the following: Elective tonsillectomy or tonsillectomy with adenoidectomy, PETs and/or EUA of ear scheduled on an out-patient basis American Society of Anesthesiologists (ASA) patient classification I-II Inclusion Criteria 8

Pre-existing allergy or known hypersensitivity to acetaminophen Midazolam as a premedication Hepatic impairment or severe active liver disease History of chronic malnutrition Severe renal impairment Severe hypovolemia ASA physical status III or greater Exclusion Criteria 9

Subject is assigned to one of 2 groups: IV Acetaminophen (15mg/kg) or Placebo Study group assignment sealed in an envelope with identifier for disclosure before discharge Volume of NS equal to the volume that would be administered from IV acetaminophen group given in the same manner and at the same time as the acetaminophen group Randomization provided in groups of 3 by statistician to pharmacy Separate randomization for ages 3-5 and 6-10 Study Protocol 10

Clinical Research Coordinator (CRC) will prescreen tonsillectomy patients the week prior to their surgery and will call for preliminary consent Once patient is in the pre-op area, the CRC will explain the study purpose and protocol and will obtain signed parental consent Then attending anesthesiologist will order study agent in Epic (double blinded to CRC and all direct care givers) CRC will notify the Investigational Pharmacy who will prepare the study agent and sealed envelope with treatment assignment Post-op orders will be written to follow opioid dosing (fentanyl 0.5 mcg/kg for moderate or severe pain) according to guidelines Preperative Procedures 11

After induction 0.1 mg/kg morphine will be given prior to intubation Study agent will be given after patient is intubated and ready for start of surgery Fentanyl up to 1 mcg/kg may be given intraop No other specifications for anesthetic technique Zofran & Decadron per usual (recorded) Patient may be taken to PACU with or without ETT (extubated deep or awake) Operating Room Procedures 12

Data collection begins when the patient is deemed awake Fentanyl 0.5 mcg/kg every 5 minutes for 30 minutes will be ordered (can be extended) for moderate or severe pain PACU RN and CRC will confer on FLACC and PAED scores every 5 minutes All medications, adverse events and vital signs recorded by CRC At discharge readiness, the PACU Nurse will open sealed envelope to reveal study treatment assignment. At that point, teaching for next dose of Tylenol product may occur. PACU Procedures 13

Primary Outcome: FLACC pain scores in PACU http://pain.about.com/od/testingdiagnosis/ig/pain-scales/Flacc-Scale.htm Outcomes 14

Secondary Outcomes: Number of rescue doses of fentanyl in PACU Incidence of respiratory depression (O2 sat<94%) Presence of nausea and/or vomiting Excessive sedation (prolonged PACU stay) Quality of emergence as measured by the PAED scale focusing on agitation Outcomes 15

PAED Scale Pediatric Anesthesia Emergence Delirium Scale Outcomes 16

Primary outcomes: Wilcoxon Mann Whitney test Secondary outcomes: Non-parametric analysis of longitudinal data Chi-squared and Fisher s exact for categorical variables Two-sided with significance level of alpha = to or < 0.05 R Studio Version 3.3.2 Bonferroni correction of alpha for multiple comparisons Statistical Methods 17

Goal is to gain definitive information on the analgesic efficacy of IV acetaminophen and the opioid-sparing potential of the drug in healthy pediatric tonsillectomy patients Future benefit of using this drug for less healthy patients who cannot tolerate morphine especially those with sleep disordered breathing Diminish or prevent other adverse outcomes associated with opioids in pediatric tonsillectomy patients Potentially provide overall cost-effectiveness with IV acetaminophen use by decreasing post-op complications and extended stays without adding unnecessary cost to the anesthetic/patient Conclusions 18

Preliminary Results: Age Distribution 19

Preliminary Results: BMI Distribution 20

Preliminary Results: ASA Distribution 21

Preliminary Results: FLACC Scores in PACU 22

Preliminary Results: # of Fentanyl Doses in PACU 23

Preliminary Results: Total Narcotic Given 24

Preliminary Results: PAED Scores 25

Preliminary Results: PACU Length of Stay Differences 26

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