Dexmedetomidine as a Pediatric Anesthetic Premedication to Reduce Anxiety and to Deter Emergence Delirium Renee Vicari RN, BSN, CCRN, SRNA Oakland University/Beaumont Hospital Graduate Program of Nurse Anesthesia

Mountain, BW. , Smithson, L. , Cramolini, M. , Wyatt, TH. , Newman, M Mountain, BW., Smithson, L., Cramolini, M., Wyatt, TH., Newman, M. (2011). Dexmedetomidine as a pediatric anesthetic premedication to reduce anxiety and to deter emergence delirium. AANA Journal, 79(3), 219-224.

Introduction Published in the June 2011 issue of American Association of Nurse Anesthetists (AANA) Journal. Study was approved by both an affiliated university and the hospital institutional review board.

Key Terms! Emergence Delirium (ED)- is a mental disturbance common in children during recovery from general anesthesia. Symptoms: Combative movements Thrashing, excitability Disorientation Inconsolable crying Studies also report that the incidence of ED in children ranges from 20-30%. Why is this important to us as anesthesia providers? During ED, children risk injuring themselves by dislodging IV tubes or drains, bleeding from OR site, hurting themselves or others and increasing their pain level.

Purpose of Study To compare the effects of oral dexmedetomidine and midazolam in reducing anxiety and ED in children aged 1 to 6 years receiving dental restoration.

Review of Literature Kain and colleagues reported that pre-operative anxiety may be linked to emergence delirium. 54% of their subjects had negative behavior patterns at 2 weeks and 20% of these continued for up to 6 months. Follow-up study found that children with pre-operative anxiety had a higher excitement score in PACU and negative behaviors at home. Bad dreams Waking up crying Separation anxiety Temper tantrums

Review of Literature Sevoflurane, perioperative medications and pain increase ED. Midazolam most common medication used pre-op to reduce anxiety. Dexmedetomidine IV shown to reduce ED when given intraoperative. Limited studies on dexmedetomidine use in children Restricted to IV use Dexmedeteomidine shows promise as a medication to reduce anxiety and potentially reduce the occurrence or severity of ED.

Hypothesis 2 Part Hypothesis: Oral dexmedetomidine is as effective as midazolam in reducing anxiety, as measured by tool assessing separation from parent and acceptance of mask, prior to surgery. Oral dexmedetomidine reduces the incidence and severity of ED in pediatric population.

Study Randomized Prospective Double-blinded design Children were recruited to participate in this study by receiving a packet of information once their dental restoration surgical procedures were scheduled. Families who received the information were contact by phone to determine their interest in the study and to help answer any questions regarding the study.

Inclusion Criteria Included 41 children Aged 1 to 6 years old Undergoing dental restorations and possible tooth extraction.

Exclusion Criteria Known allergies to midazolam and or dexmedetomidine Developmental delay or mental retardation-as reported by the parents History of ED ASA classification greater than II Any previous reactions to anesthesia

Methods Obtained informed consent Subjects were randomly assigned to 1 of 2 groups Control group: Received 0.5mg/kg of oral midazolam Experimental group: Received 4mcg/kg of oral dexmedetomidine Staff and members of research team blinded to assignments and medication administered.

Methods Both medications were prepared in similar syringes Prepared with cherry-flavored syrup

Dexmedetomidine (Precedex) Non-selective alpha-2 adrenergic agonist Sedative and opioid sparing effects Expensive-$495.79 IV infusion-0.2-0.7mcg/kg/hr Minimal respiratory depression Adverse effects: N/V Bradycardia Hypotension Fever In the heart, alpha agonists decrease tachycardia through the block of the cardioaccelerator nerve and produce bradycardia through the vagomimetic action. In the peripheral vasculature, there are both vasoldilatory action through sympatholysis and vasoconstriction by direct action on the alpha adrenceptors on smooth muscle cells.

Midazolam (Versed) Benzodiazepine Amnestic and anxiolytic properties 0.5mg-1.0mg/kg PO in children Adverse effects: Headache Drowsiness Confusion N/V Blood pressure changes

Instruments 3 instruments used Parental Separation Anxiety Scale (PSAS) -4 point scale 1=easy separation 2=whimpers, but is easily reassured, not clinging 3=cries and cannot be easily reassured, but not clinging to parents 4=crying and clinging to parents PSAS of 1-2 acceptable PSAS of 3-4 were difficult separations

Instruments Mask Acceptance Scale (MAS)-ability to accept the anesthesia mask MAS scale is a 4-point Likert scale 1=excellent (unafraid, cooperative, accepts mask readily) 2=good (slight fear of mask, easily reassured) 3=fair (moderate fear of mask, not calmed with reassurance) 4=poor (terrified, crying, or combative) Score of 1-2 was satisfactory Score of 3-4 was unsatisfactory

Instruments Pediatric Anesthesia Emergence Delirium Scale (PAEDS) Based on 5 criteria: Makes eye contact with caregiver Actions are purposeful Aware of his or her surroundings Restless Inconsolable Out of 20 points, a score greater than 10 indicates ED. All research members were trained on data collection and how to score each tool to ensure interrater reliability of rating scales.

Data Analysis Pearson X2 analysis was performed to determine differences between both groups for anxiety Independent sample t test was used to determine differences between occurrence and severity of ED in both groups. Level of significance was set at P=0.05

Procedures Study medication administered 30 minutes prior to OR Pulse oximetry and blood pressure monitored every 15 minutes Research team member accompanied child to surgery and the PSAS was scored at this time-30 minutes after child received medication In OR with nurse anesthetist, team member calculated the MAS score

Procedures Study anesthesia protocol: Mask induction with sevoflurane and nitrous oxide Isoflurane used for maintenance Spontaneous ventilation was maintained if possible Muscle relaxants were avoided, if possible, if ventilatory support needed. Anticholinergic drugs were avoided Odansetron (0.2mg/kg) and dexamethsone (0.25mg/kg) were administered Fentanyl for analgesia (1 to 2 mcg/kg) Local anesthestic per surgeon

Procedures Taken to PACU after surgery Observed for 1 hour PAEDS score was determined once child aroused or peak of ED

Results 41 subjects recruited between May 2006 and June 2007 21 (51%) males 20 (49%) females Mean age 4 years old 27 (65%) white 9 (22%) African American 5 (12%) Hispanic

Results No difference in mean blood pressure values in the 2 groups (t=0.852, P=0.399) No difference in the pulse oximetry values in the 2 groups (t=0.459, P=0.649) No difference in separation from parents between the 2 groups (X2=0.478, P=0.489) No statistically significant differences between the 2 group with acceptance of the anesthesia mask (X2=0.602, P=0.438)

Results

Results Out of 41 subjects 8 children (20%) experienced ED 3 of the 8 were in the experiemental (dexmedetomidine) group 5 were in the control (Midazolam) group No significant difference between the 2 groups (t=1.023, P=0.313)

Discussion Study was able to demonstrate that 4mcg/kg PO of dexmedetomidine resulted in no adverse effects No difference between the midazolam and dexmedetomidine groups in blood pressure or oxygenation stability

Strengths Double-blinded study All subjects remained in study Equal number of males and females Detailed and precise anesthesia protocol while child is anesthetized Specific surgery-all subjects underwent same surgery

Limitations Limited sample size Absence of fluctuations in blood pressure and heart rate (common side effect) with dexmedetomidine may indicate that 4 mcg/kg was too low to be clinically effective. Used oral dexmedetomidine instead of buccal Bioavailability is 16% (oral) compared to 82% (buccal)

Conclusion Not FDA approved for children….yet More studies needed to examine child-friendly dexmedetomidine preparations and its effect on ED