Comparison of Dexmedetomidine as bolus or low – dose infusion to prevent postoperative agitation.

Completed

• Conditions: Other specified disorders of urinary system,

• Registration Number: CTRI/2018/10/016088

Brief Summary

**Introduction**

Sevoflurane is a preferred inhalational anesthetic for both induction and maintenance of general anaesthesia in children because it is characterized with rapid onset and offset of anesthesia and causes less irritation to the airway[[1](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR5)]. However, sevoflurane is associated with a high incidence of emergence agitation which may delay patient discharge from PACU and there from the hospital [[2](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR5)–[5](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR8)]. Emergence agitation has the risks of self-injury, extra nursing care, family dissatisfaction and increased cost [[6](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR9)].

Dexmedetomidine, a highly selective α-2 receptor agonist and is commonly used in adult anesthesia and intensive care [[7](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR10)–[9](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR12)]. Dexmedetomidine is also beneficial in the perioperative period of pediatric patients. It’s anxiolytic, sedative, and analgesic properties are beneficial for emergence agitation control [[6](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR9), [1](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR13)0].

This study is being designed to evaluate the efficacy of dexmedetomidine bolus or infusion for controlling emergence agitation with sevoflurane anesthesia in pediatric patients.

**REVIEW OF LITERATURE:**

**Kim et al (2014)** tested whether the addition of an intra-operative low-dose infusion of dexmedetomidine to fentanyl treatment reduced the inci­dence of emergence delirium following desflurane anesthesia in children undergo­ing strabismus surgery. They concluded that intra-operative low-dose infusion of dexmedetomidine in addition to fentanyl reduces EA following desflurane anaesthesia in children undergoing stra­bismus surgeries.

**Hauber et al (2015)** examined the effect of rapid IV bolus injection of DEX on emergence agitation and the hemodynamic response in a large sample of children undergoing tonsillectomy with or without adenoidectomy, with or without myringotomy, and/or tympanostomy tube insertion. They concluded that rapid IV bolus administration of DEX in children improved their recovery profile by reducing the incidence of EA. A statistically significant change in hemodynamics was observed, but no patients required any intervention for hemodynamic changes. Furthermore, DEX reduced the incidence of postoperative opioid administration, and a trend of fewer adverse events was observed in group DEX.

**Bedirli et al (2017)** compared the efficacy of an intraoperative single dose administration of tramadol and dexmedetomidine on hemodynamics and postoperative recovery profile including pain, sedation, emerge reactions in pediatric patients undergoing adenotonsillectomy with sevoflurane anesthesia. They concluded that both tramadol and dexmedetomidine were effective for controlling pain and emergence agitation. When compared with tramadol intraoperative hypotension, bradycardia and prolonged sedation were problems related with dexmedetomidine administration.

 **AIMS AND OBJECTIVES**

1.         To compare the efficacy of dexmedetomidine bolus and infusion on emergence agitation in pediatric patients after sevoflurane anaesthesia.

2.         Side effects or complications, if any.

**MATERIAL AND METHODS**

**Study Design**: Randomised, double-blind, comparative study.

MethodsAfter obtaining approval from the ethics committee of the university, a written informed consent from the parents/guardians would be obtained. Patients of ASA physical status I–II, aged 2–10 years of either sex with + 20% of ideal body weight, would be enrolled in this prospective, randomized, double blind study. Patients with history of developmental delay, cardiac disorders, psychological disorders, epilepsy and allergy to study medications would be excluded from the study.

Standard monitoring including electrocardiogram, noninvasive blood pressure, pulse oximetry and inspiratory and expiratory gas concentrations would be done. Anesthesia would be induced with 8% inspired sevoflurane and 60% nitrous oxide in oxygen by facemask. After induction an intravenous catheter would be inserted and 1 Î¼g/kg intravenous (iv) fentanyl would be given as bolus and rocuronium 0.6 mg/kg would be administered to facilitate endotracheal intubation.

Patients would be assigned to one of two groups according to a computer generated random number table. After intubation patients in Group-I would receive bolus dexmedetomidine over 10 min and the patients in Group-II would receive continuous infusion of dexmedetomidine throughout the procedure. Heart rate (HR), mean arterial pressure (MAP) and peripheral oxygen saturation (SpO2) would be recorded before induction (baseline), at induction and every 5 min after induction during the procedure.

For maintenance of anesthesia, patients would receive 2% sevoflurane in 60% N2O and 40% oxygen with controlled ventilation to maintain normocapnia. In both groups 25% increase in HR and MAP with respect to the baseline value before anesthesia induction and sustained for 5 minutes would be considered as tachycardia and hypertension and would be treated with 0.5 mg/kg fentanyl. Likewise, 25% decrease in HR and MAP is defined as bradycardia and hypotension, respectively. Atropine 0.01 mg/kg intravenously for bradycardia and 10 ml/kg Ringer’s lactate solution for hypotension would be administered to the patients. Intraoperative dexamethasone 0.5 mg/kg (maximum 10 mg), ondansetron 0.1 mg/kg and antibiotics would be administered to all patients according to institutional practice. Ringer’s lactate solution would be administered for fluid management to all the patients.

After completion of surgery, when hemostasis would be achieved, anesthetic gases would be discontinued and neuromuscular blockade would be reversed with neostigmine 0.05 mg/kg and atropine 0.02 mg/kg iv. The trachea would be extubated when patients would have eye opening, purposeful movement, or response to command and thereafter patients would be transferred to post anesthesia care unit (PACU). The duration between the termination of anesthetic gases and the extubation would be defined as ‘extubation time’.

In PACU the intensity of pain would be assessed by using a modified Hannallah pain score[[11](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR21)] – an observational pain score (OPS). Moreover, pediatric anesthesia emergence delirium (PAED) scale[[12](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR22)], Ramsay sedation score (RSS)[[13](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5346230/#CR23)], HR, MAP and SpO2 would be measured and recorded on arrival to PACU and 5, 10, 15, 30, 45, 60 min thereafter. Besides these any adverse effects such as vomiting, airway obstruction, laryngospasm or bronchospasm, bradycardia, hypotension, sedation would be recorded. All these measurements and recordings would be done by the anaesthetist or nurse who would be blind to the group of the patient.

The number of patients who presented with OPS ≥ 4 or PAED scale items 4 *‘the child is restless’* or 5 *‘the child is inconsolable’* with an intensity of 3 (very much) or 4 (extremely) would be recorded and 15 mg/kg paracetamol as rescue analgesic would be administered to these patients. Patients who had an Alderete score > 9 would be discharged from PACU to surgical ward. The duration between admission to PACU and discharge from PACU to surgical ward would be defined as ‘time to reach Alderete score > 9’.

Duration of surgery and anesthesia, extubation time, need for supplemented analgesic, the incidence of vomiting during the 60 min period, and time to reach Alderete score > 9 would be recorded.

Statistical analysisSample of 24 patients in each group is calculated to detect 25% difference in the incidence of emergence agitation with dexmetomediine bolus and low dose infusion with 0.05 of a and 0.8 of b using power analysis sample size software. To increase the power of study and assuming some of the drop outs, we will include 30 patients in each group.

 **REFERENCES:**

1.         Lerman J. Inhalation agents in pediatric anaesthesia-an update. Curr Opin Anaesthesiol. 2007;20:221–6.

2.         Cole JW, Murray DJ, McAllister JD, Hirshberg GE. Emergence behaviour in children: defining the incidence of excitement and agitation following anaesthesia. Paediatr Anaesth. 2002;12:442–7.

3.         Kuratani N, Oi Y. Greater incidence of emergence agitation in children after sevoflurane anesthesia as compared with halothane: a meta-analysis of randomized controlled trials. Anesthesiology. 2008;109:225–32.

4.         Voepel-Lewis T, Malviya S, Tait AR. A prospective cohort study of emergence agitation in the pediatric postanesthesia care unit. Anesth Analg. 2003;96:1625–30.

5.         Sun L, Guo R, Sun L. Dexmedetomidine for preventing sevoflurane-related emergence agitation in children: a meta-analysis of randomized controlled trials. Acta Anaesthesiol Scand. 2014;58:642–50.

6.         Barr J, Fraser GL, Puntillo K, Ely EW, Gélinas C, Dasta JF, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41:263–306.

7.         Mantz J, Josserand J, Hamada S. Dexmedetomidine: new insights. Eur J Anaesthesiol. 2011;28:3–6.

8.         Arain SR, Ruehlow RM, Uhrich TD, Ebert TJ. The efficacy of dexmedetomidine versus morphine for postoperative analgesia after major inpatient surgery. Anesth Analg. 2004;98:153–8.

9.         Mahmoud M, Mason KP. Dexmedetomidine: review, update, and future considerations of paediatric perioperative and periprocedural applications and limitations. Br J Anaesth. 2015;11:171–82.

10.       Hannallah RS, Broadman LM, Belman AB, Abramowitz MD, Epstein BS. Comparison of caudal and illeoinguinal/iliohypogastric nerve blocks for control of post-orchiopexy pain in pediatric ambulatory surgery. Anesthesiology. 1987;66:832–4.

11.       Sikich N, Lerman J. Development and psychometric evaluation of the pediatric anesthesia emergence delirium scale.  Anesthesiology.  2004;100:1138–45.

12.       Ramsay MA, Savage TM, Simson BR. Controlled sedation with alphaxalone-alphadolone. Br Med J. 1974;2:656–9.

13.   [Bedirli N](https://www.ncbi.nlm.nih.gov/pubmed/?term=Bedirli%20N%5BAuthor%5D&cauthor=true&cauthor_uid=28283018), [Akçabay M](https://www.ncbi.nlm.nih.gov/pubmed/?term=Ak%C3%A7abay%20M%5BAuthor%5D&cauthor=true&cauthor_uid=28283018), [Emik U](https://www.ncbi.nlm.nih.gov/pubmed/?term=Emik%20U%5BAuthor%5D&cauthor=true&cauthor_uid=28283018). Tramadol vs dexmedetomidine for emergence agitation control in pediatric patients undergoing adenotonsillectomy with sevoflurane anesthesia: prospective randomized controlled clinical study. [BMC Anesthesiol.](https://www.ncbi.nlm.nih.gov/pubmed/28283018 "BMC anesthesiology.") 2017;17:41-8.

14.  [Hauber JA](https://www.ncbi.nlm.nih.gov/pubmed/?term=Hauber%20JA%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Davis PJ](https://www.ncbi.nlm.nih.gov/pubmed/?term=Davis%20PJ%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Bendel LP](https://www.ncbi.nlm.nih.gov/pubmed/?term=Bendel%20LP%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Martyn SV](https://www.ncbi.nlm.nih.gov/pubmed/?term=Martyn%20SV%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [McCarthy DL](https://www.ncbi.nlm.nih.gov/pubmed/?term=McCarthy%20DL%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Evans MC](https://www.ncbi.nlm.nih.gov/pubmed/?term=Evans%20MC%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Cladis FP](https://www.ncbi.nlm.nih.gov/pubmed/?term=Cladis%20FP%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Cunningham S](https://www.ncbi.nlm.nih.gov/pubmed/?term=Cunningham%20S%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Lang RS](https://www.ncbi.nlm.nih.gov/pubmed/?term=Lang%20RS%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Campbell NF](https://www.ncbi.nlm.nih.gov/pubmed/?term=Campbell%20NF%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Tuchman JB](https://www.ncbi.nlm.nih.gov/pubmed/?term=Tuchman%20JB%5BAuthor%5D&cauthor=true&cauthor_uid=26332857), [Young MC](https://www.ncbi.nlm.nih.gov/pubmed/?term=Young%20MC%5BAuthor%5D&cauthor=true&cauthor_uid=26332857). Dexmedetomidine as a rapid bolus for treatment and prophylactic prevention of emergence agitation in anesthetized children. [Anesth Analg.](https://www.ncbi.nlm.nih.gov/pubmed/26332857 "Anesthesia and analgesia.") 2015;121:1308-15.

15.     Jeongmin Kim, So Yeon Kim, Jae Hoon Lee, Young Ran Kang, and Bon-Nyeo Koo. Low-Dose Dexmedetomidine reduces emergence agitation after desflurane anaesthesia in children undergoing strabismus surgery.  Yonsei Med J 2014;55:508-16.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-01-03
• Study Completion: 2018-01-08
• Last Update Posted: 2018-10-17

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

Patients of ASA physical status I–II, aged 2–10 years of either sex with + 20% of ideal body weight, would be enrolled in this prospective, randomized, double blind study.

Exclusion Criteria

Patients with history of developmental delay, cardiac disorders, psychological disorders, epilepsy and allergy to study medications would be excluded from the study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To see emergence agitation by using PAEDS scale,pain by using OPS score and sedation by using RSS score.	Postoperatively for one hour

Secondary Outcome Measures

Name	Time	Method
DRUG MORE EFFECTIVE FOR PREVENTION OF EMERGENCE AGITATION WITH BOLUS OR LOW DOSE INFUSION OF DEXMEDETOMIDINE	ONE YEAR

Trial Locations

Locations (1)

KING GEORGES MEDICAL UNIVERSITY; 🇮🇳 Lucknow, UTTAR PRADESH, India

KING GEORGES MEDICAL UNIVERSITY

🇮🇳Lucknow, UTTAR PRADESH, India

UZMA BEGUM

Principal investigator

8176861027

uzmabegum09@gmail.com