Emergence agitation (EA) is a common problem in pediatrics patient undergoing general anesthesia with sevoflurane, which can manifest as confusion, crying, excitation, thrashing, pain and continues to be in early recovery period. Emergence agitation can not only distress the child and their families in early recovery period but can become neurological complication and manifest as delirium with post operative behavioral changes in long term.

Sevoflurane is choice of inhalational agent uses for induction and maintenance of anaesthesia in paediatrics. Sevoflurane is used for its efficacy, smooth induction, maintenance with little hemodynamic changes, low solubility and rapid emergence. However it is noted with sevoflurane, the incidence is seen in up to 80% of patients[3], who experiences agitation in early emergence period.

Emergence agitation with restlessness, inconsolable cry, thrashing can lead to self extubation, disconnection with vitals monitors, self-removal of indwelling catheters, bleeding, ripping of sutures, physical fall, and can land into major hemo-dynamical changes that may risk life of the patient.

 Thus, Emergence from anaesthesia must be smooth and less stressful to patient and their families, to health care professional in peri-operative and post operative care unit. It is essential to prevent EA, and diagnose so as to reduce the early complications as well as in long term which can lead to delirium with post operative behavioural changes.

Emergence delirium (ED) was first described by Eckenhoff and colleagues in the1960s. The incidence is two to three times more common in children. It varies from 20-80% of all the patient emergence from general anaesthesia.

The mechanism behind the agitation is still poorly understood, however the common factors related to it in paediatrics is listed as pain, alien environment, unknown faces, physical restraints, parental separation, presence of indwelling catheters. EA is self-limited and occurs more in early 30 minutes of emergence in post anaesthetic care unit (PACU) in most of the patients, but use of pharmacological interventions remains to be a better method to prevent or treat it. Different studies showed use of Ketamine, Dexmedetomidine, TIVA, fentanyl, ketofol, midazolam as pre-medication or intraoperative intra-venous administration has effectively reduced the incidence of EA.

Dexmedetomidine is new drug, highly selective alpha2 adrenergic receptor agonist, has sedative and analgesics effect, used clinically in reducing peri-operative anxiolysis, sedation, analgesia sparing, in critical area setting for awake sedation.

Dexmedetomidine is a highly lipophilic drug with a high volume of distribution (V_D) in both children and adult. It is predominantly bound to plasma proteins (>90%), primarily albumin and glycoprotein alpha1. It crosses the blood brain barrier and has a V_D in children older than 1year similar to adult values.

It is thought to fit a two-compartment model with first order elimination, showed a rapid and wide distribution throughout the body, and has a short elimination half-life of 2hours.

It produces sedative effect via alpha2 adrenoreceptors in the locus coeruleus in the central nervous system, by blocking the sympathetic outflow, thereby inhibiting the release of nor-epinephrine.

It is eliminated mainly through biotransformation by the liver-by the enzymes uridine5’-diphospo-glucuronosyl-transferase and cytochrome P450 to inactive metabolites and direct glucuronidation, which are excreted in bile and through renal pathways.

The side effects are limited to hemodynamical alterations, includes hypertension, hypotension, bradycardia owing to pre- and post synapticalpha2-receptors activation, which causes vasoconstriction, vasodilation and reflex bradycardia.

The use of dexmedetomidine has increased for paediatric anaesthesia in these years, as it provides satisfactory effect in attenuating the hemodynamic responses to intubation and extubation, addition to regional anaesthesia gives prolonged and analgesia sparing effect, reduces EA, and gives a similar sedative effect with little or no respiratory effect. However, in children IV administration reported episodes of bradycardia, hypotension requires close and prolonged monitoring.

So, nebulised dexmedetomidine may be a better alternative route, as nasal mucosa accounts for 65% and buccal mucosa accounts for 82% bio-availability of drug, with less adverse effects.

This study aims to use the Dexmedetomidine in form of nebulisation for the prevention of sevoflurane induced EA in children aged 2-8years.

MATERIALS AND METHOD:

Ø Inclusion criteria:

-Patients whose parent/guardian had given written informed consent.

 -Patients belonging to ASA grade I and II.

- Both genders.

- Patients in the age group of 2-8 years.

- Patients undergoing elective surgery under GA with sevoflurane for maintenance of anesthesia.

Ø Exclusion criteria:

-Patient’s parent/guardian refusal.

-Patient with development delay.

- Anticipated difficult intubation.

0 Emergency surgeries. 

-Patient having h/o asthma, known allergy to the drug, or any cardiac disease.

-Usage of Inhalational induction. 

-Infusion propofol and/or dexmedetomidine is used for maintenance of anesthesia.

-Patients required post operative ventilatory support.

Ø Study setting: SGPGIMS, Lucknow.

Ø Sample size: 120 patients will be taken, 40 patients in each group A, group B and group C (including ± 10% drop out) 

Ø Study design: Double blinded Randomized controlled study.

Hence, we plan to include 120 patients which are randomly distributed among the group in 1:1:1, predefined using MS excel, and kept sealed. The patient and observer will be unaware of the group being allocated.

Methodology:

After obtaining approval from the institutional ethics committee of SGPGIMS and written informed consent from the parent of patients, the study will be conducted with the study population being the patients aged 2-8years of both gender, ASA I and II, undergoing elective surgery in GA with sevoflurane.

 Patients will be randomly allocated in 3 groups- A, B and C, which will be predefined as serial number, will be kept in a sealed envelope and allocation concealment will be maintained. The patient and observer will be unaware of the drug. Primary observer who will know the serial number and allocated group will prepare drug and handed over to resident in OT, who will give drug to the patient, later will observe and record the findings.

According to allocated group, Group A will be receiving 0.5µg/kg Dexmedetomidine in 3ml volume through nebulization.

Group B will be receiving 1µg/kg Dexmedetomidine in 3ml volume through nebulization.

Group C will be receiving normal saline-3ml in volume through nebulization. Group C will be considered as control group.

All children allocated in both groups must fast 8hrs for solid, 6hrs for semi-solid and 1hr for clear fluid. Patients will be taken to operating theatre. All ASA standards monitor will be attached. IV Fluids will be connected and maintenance fluid will be started as per standard. All patient will receive Ketamine 1mg/kg iv and Glycopyrrolate 0.01mg/kg in pre-operative area. With the onset of sedation, pt will be taken to operation theatre, and will be preoxygenated with 100% oxygen via mask for 3 minutes. All patient will be induced with IV Propofol 2mg/kg, fentanyl2mcg/kg and neuro-muscular blockade (Vecuronium 0.1mg/kg IV or Atracurium 0.5mg/kg /IV or cis-atracurium 0.1mg/kg IV). The airway will be secured as per standard size. The plane of anesthesia will be maintained with sevoflurane and O₂: air-1:1 in both the groups and with neuro-muscular blockade (Vecuronium 0.1mg/kg IV or Atracurium 0.5mg/kg /IV or cis-atracurium 0.1mg/kg IV). All patients will be ventilated to keep end tidal volume between 30-35.

Patients will be nebulized with 3ml volume containing 0.5µg/kg dexmedetomidine in Group A, 1µg/kg dexmedetomidine in B group, and 3ml of normal saline in group C -30 minutes before the end of surgery (at the start of suturing) till the entire volume of drug dispersed. At the end of surgery, when extubation criteria is met, sevoflurane will be turned to zero at the MAC of 1. Patient will be receiving neuro muscular blockade reversal containing Neostigmine bromide 20mcg/kg and glycopyrrolate 10mcg/kg, and endotracheal tube will be removed. O₂ 6l/min will be administered via face mask.

The time after extubation, first response to verbal command or eye opening is emergence time, will be recorded.

All patients will be shifted to post anesthesia care unit (PACU), and following parameters will be recorded:

·      Emergence agitation (EA) will be measured using CRAVERO Scale at 30 min, at 45 min and at 60 minutes of nebulization.

·      Hemodynamic parameters: Heart rate (HR), SPO2, Non-invasive Blood Pressure (NIBP), Respiratory rate (RR) at 45 min, and 60 minutes of nebulization.

·      Any adverse event at any point of time peri-operatively after nebulization will be recorded in form of type, duration and management.

·      In case of prolonged extubation (beyond 45 min after nebulization), EA and Hemodynamic parameters will be recorded at the time of extubation.

In case of any adverse effect, patient will be treated accordingly. In case of known adverse effect- bradycardia- patient will be given atropine 0.1mg/kg (as per standard guidelines), hypotension- patient will be given bolus of maintenance fluid and close monitoring.