بسم الله الرحمن الرحيم ( هُوَ الَّذِي أَنْزَلَ السَّكِينَةَ فِي قُلُوبِ الْمُؤْمِنِينَ لِيَزْدَادُوا إِيمَانًا مَعَ إِيمَانِهِمْ )   * الفتح/4

Dextromethorphan Premedication Before Strabismus Surgery Reduces Sevoflurane-Emergence Agitation Ahmed M. Khattab (M.D.) * (Presenting Author) Zeinab A. El Seify (M.D.) ** Ayman A. Elrashidy (M.D.) *** *Associate Professor of Anesthesia, Faculty of Medicine, Ain Shams University, Cairo, Egypt & Consultant anesthesiologist, Queen Medical, Doha, Qatar. ** Consultant Anesthesiologist Al-Ahli Hospital, Doha, Qatar. *** Associate Professor of Anesthesia, Faculty of Medicine, Tanta University, Tanta, Egypt & Consultant Anesthesiologist, Al-Magrabi Hospital, Doha, Qatar.

INTRODUCTION The Quality of anesthesia Induction & Recovery is the cornerstone of ambulatory pediatric anesthesia. Choosing Sevoflurane as an induction agent for children will provide: well tolerability, rapid induction, and prompt recovery making it a preferred choice. However, Emergence Agitation (EA) is the major disadvantage of sevoflurane anesthesia (up to 80 %). Various Pharmacological & Non-pharmacological techniques → unsatisfactory outcome. No single technique proved to be completely effective; and even delayed recovery which might affect the hospital discharge was reported.

INTRODUCTION • Ideal Combination should be: • Postulated Causes of EA might include: increased pain sensation, anxiety, intrinsic characteristics of sevoflurane, and/or rapid emergence with variable neurological recovery. If →→ (Multifactorial Causes !!) ←← Think in →→ (Multimodal Management) ←← • Ideal Combination should be: *Prophylactic (rather than postoperative). *Orally administered with Favorable Pharmacokinetics. *Wide Safety Margin. *Suitable Duration of Action. • Due to their antihyperalgesic and analgesic-sparing effects when used in single small doses, N-methyl-D-aspartate (NMDA) receptor antagonists (ketamine, Magnesium, and dextromethorphan) become an essential component of multimodal and preemptive analgesia. Accordingly, recent clinical trials started to focus the light on their possible prophylactic role in the prevention of EA. • The efficacy of oral dextromethorphan as a prophylactic & supplementary measure in prevention of EA was not yet fully tested.

AIM of the STUDY The primary aim of this study was to test the efficacy of Supplementing Dextromethorphan to Midazolam premedication in reducing the incidence & severity of Emergence Agitation among children undergoing strabismus surgery under sevoflurane anesthesia. & VS. alone ??

PATIENTS & METHODS • Study Design: Prospective, Randomized, Double-blind, and Controlled clinical trial. • Sittings: Day Care Center (Operating Room and PACU) . • Patients: 72 Children (ASA I or II) aged 4 - 7 years, scheduled for Strabismus Surgery under Sevoflurane anesthesia. • Patient Allocation & Intervention: children were randomly allocated into Two Groups; 36 patients each: 1) Control Group (M) children premedicated with oral Midazolam in a dose of (0.5 mg/kg). 2) Study Group (MD) premedicated with the same dose of Midazolam in combination with Dextromethorphan syrup (Dextrokuf® 3 mg/mL) in a dose of (1 mg/kg). * The medicines were mixed with apple juice . The volume of apple juice was adjusted to reach a total syringe volume of 10ml in both groups. *Sevoflurane Inhalation Induction. *LMA. *Multimodal Analgesia. *PONV Prophylaxis.

PATIENTS & METHODS • Measurements: 1) The incidence and severity of EA were evaluated with the validated Pediatric Anesthesia Emergence-Delirium (PAED) scale. * Five items, each item scored from 1→4. The scores were summed to obtain a total “Scale Score”. * The child was considered agitated if his PAED score was 10/20 or more, severe agitation was considered with a score of 16/20 or higher . 2) Agitated children were managed by intravenous increments of fentanyl 1μg.kg-1 Total Consumption of Rescue Fentanyl was recorded. 3) Recovery and PACU Discharge-Readiness Times. 4) Possible Complications or Side Effects.

Severely Agitated (>16) RESULTS P Value GROUP MD (Study = 36 pts.) GROUP M (Control = 36 pts.) 0.016 3/36 (8.3%) 2/36 (5.5%) 11/36 (30.5%) 5/36 (13.8%) PAED score in (PACU): Total No. Agitated (%) Severely Agitated (>16) 0.012 1.52 ± 5.18 7.08 ± 11.8 Postoperative (Rescue) Fentanyl Consumption (µg): 0.029 ??? 7.6 ± 0.9 6.7±1.3 Time to Recovery from Anesthesia (min.): 0.0019 16.72 ± 4.9 20.16 ± 4.9 PACU Discharge-Readiness Time (min): 2 children = PONV Non Postoperative Complications:

RESULTS

DISCUSSION & CONCLUSION • Although dextromethorphan is structurally related to opioids and it has antitussive activity approximately equal to that of codeine, it has NO apparent activity at mu or kappa receptors and does NOT produce a typical opioid syndrome in overdose. • It is well absorbed orally, and effects are often apparent within 15–30 minutes (peak of action at 2–2.5 hours) = Favorable Pharmacokinetics to be used as a Premedication Drug. • Emergence Agitation (EA) or Emergence Delirium (ED) ????? • Preoperative Anxiety? ± Pain? ± Intrinsic Criteria of Sevoflurane? ± Differential Neurological Recovery? = Multifactorial ?? • Dextromethorphan is having neuroprotective, anticonvulsant, and antinociceptive activities with high affinity binding to several regions of the brain. = Multimodal Actions ??

DISCUSSION & CONCLUSION Adding dextromethorphan to midazolam-based oral premedication in children undergoing strabismus surgery could be an effective and safe combination in reducing the incidence of emergence agitation.