Effect of Single-Dose Dexmedetomidine on Intraoperative Hemodynamics and Postoperative Recovery during Pediatric Adenotonsillectomy.

BACKGROUND: In children undergoing adenotonsillectomy, smooth recovery from anesthesia without any respiratory compromise and excessive sedation or pain is always desirable. In this placebo-controlled study, we examined the effect of single dose of dexmedetomidine on intraoperative hemodynamics and postoperative recovery profile such as emergence agitation (EA), pain, and sedation in children undergoing adenotonsillectomy.
METHODS: Sixty American Society of Anesthesiologists I or II children in the age group of 5-10 years, undergoing adenotonsillectomy were randomly assigned to receive dexmedetomidine 1 μg/kg (Group D) or volume-matched saline (placebo) (Group C), 10 min before induction of anesthesia. Intraoperative heart rate (HR) and mean blood pressure (MBP), duration of surgery, time to extubation, EA using Paediatric Anaesthesia Emergence Delirium (PAED) scale, level of sedation in postanesthesia care unit using Ramsay sedation score (RSS), and postoperative visual analog score (VAS) for pain were recorded and compared.
RESULTS: Dexmedetomidine group had lower HR and stable MBP, compared to the control group (P < 0.05). Postoperatively, the agitation score (PAED scale score) was statistically lower in Group D compared to Group C (13.84 ± 1.39; median 14 in Group C vs. 9.37 ± 1.33; median 9.5 in Group D; P < 0.001). All patients in Group C had PAED scale score >12, while only 6.67% of patients in Group D had PAED scale score of 12. The patients in Group D had higher RSS (2.62 ± 0.49 in Group D vs. 1.60 ± 0.50, P = 0.004); none of the patients were excessively sedated or had RSS >3. No significant difference was found in VAS score of the groups at all times, except at 0 h (P = 0.002). Time to extubation was significantly longer in the dexmedetomidine group (7.70 ± 1.62 min in Group D vs. 5.23 ± 1.91 min in Group C; P = 0.001).
CONCLUSION: Premedication of dexmedetomidine at the dose of 1 μg/kg in children undergoing adenotonsillectomy resulted in favorable effect on intraoperative hemodynamics, significant decrease in postoperative EA without causing any excessive sedation, desaturation, or any other drug-related adverse events.

INTRODUCTION

Adenotonsillectomy is a common, brief, but painful surgery carried out in children. Anesthesia for adenotonsillectomy can be challenging because of its association with obstructive sleep apnea syndrome (OSAS), opioid sensitivity, increased incidence of perioperative laryngospasm and bronchospasm, postoperative emergence delirium, pain, nausea, and vomiting.[12345] The aim of the anesthesiologist is to have a pain-free, comfortable child, without any airway compromise and excessive sedation in the recovery room. A screaming child in recovery room can be distressful for parents and recovery room staffs and may have higher chances of bleeding from the tonsillar bed. Dexmedetomidine is a highly selective α2 agonist (α2/α1-activity 1620:1), which may be beneficial in these children owing to its sedative, anxiolytic, and opioid-sparing properties with minimal respiratory depression.[6] It is also known to decrease emergence agitation (EA) and has favorable effects on intraoperative cardiovascular parameters.[7]

We designed this prospective, randomized, placebo-controlled study to evaluate the effect of preoperative use of single dose of intravenous dexmedetomidine on intraoperative hemodynamics and postoperative recovery profile such as EA, pain, and sedation in pediatric patients undergoing adenotonsillectomy.

METHODS

After obtaining approval from the Institutional Ethics Committee and written informed consent from parents or legal guardians, 60 pediatric patients of the age group of 5–10 years, belonging to the American Society of Anesthesiologists (ASA) physical Classes I and II, scheduled for elective adenotonsillectomy, were included in the study. Exclusion criteria were any contraindication to dexmedetomidine use and patients with a history of acute upper respiratory tract infection or bleeding diathesis. Patients were randomly allocated to either control or Group C, which received normal saline or Group D, which received dexmedetomidine using opaque-sealed envelope method. Preoperative fasting advised on the day of surgery as per the ASA guidelines. Premedication with oral midazolam 0.5 mg/kg was given to all the patients 30 min before shifting to the preoperative room. The child was shifted to the operating room, monitors for electrocardiogram, heart rate (HR), blood pressure, and oxygen saturation were attached, and baseline values were recorded. Intravenous access was achieved with 22G cannula and intravenous (iv) glycopyrrolate 4 μg/kg was given to decrease the oral secretions. Group D received iv dexmedetomidine 1 μg/kg infusion over 10 min before induction of anesthesia. Group C received same volume of iv saline infusion over 10 min before induction of anesthesia. Fentanyl 2 μg/kg iv was given before induction of anesthesia in all the patients. After preoxygenation for 3 min using 100% oxygen, anesthesia was induced with propofol 2 mg/kg, followed by vecuronium bromide 0.1 mg/kg to facilitate laryngoscopy and tracheal intubation. Oropharyngeal pack was then inserted into all the patients after tube fixation. Anesthesia was maintained with O2 with N2O (60:40), isoflurane 1%, and vecuronium bromide. Ondansetron 0.10 mg/kg iv was given to all the patients to prevent postoperative nausea and vomiting. Isoflurane was cutoff after removal of bilateral tonsils and confirmation of adequate hemostasis. At the end of surgery, oropharyngeal pack was removed after gentle suctioning. Patients were put in the left lateral position and N2O was discontinued. Residual neuromuscular blockade was reversed with iv neostigmine 50 μg/kg and glycopyrrolate 10 μg/kg once the patients started having respiratory efforts. Patients were closely observed and no further suctioning was done. Awake extubation of trachea was done with no-touch technique. After extubation, intravenous tramadol 1 mg/kg was given for postoperative analgesia. Patients were placed in the recovery position and transferred to postanesthesia care unit (PACU). Following parameters were recorded in the intraoperative and postoperative period:

Changes in HR and mean blood pressure (MBP) during intubation and every 5 min thereafter till next 30 min

Duration of surgery

Bleeding from surgical site/time to achieve hemostasis

Time to extubation (switching off N2O to tracheal extubation)

Extubation behavior using Paediatric Anaesthesia Emergence Delirium (PAED) scale [Appendix 1][8]

Appendix 1

Paediatric Anesthesia Emergence Delirium Score

Behavior	Not at all	Just a bit	Quite a bit	Very much	Extremely
Makes eye contact with care giver	4	3	2	1	0
Purposeful actions	4	3	2	1	0
Aware of surroundings	4	3	2	1	0
Restless	0	1	2	3	4
Inconsolable	0	1	2	3	4

Level of sedation in PACU using Ramsay sedation score (RSS)[9]

Postoperative pain using visual analog score (VAS),[10] on arrival in PACU, and then hourly for the next 4 h.

Need for rescue analgesia.

Intravenous fentanyl 1 μg/kg was administered as rescue analgesia, when patients had VAS >4. Any desaturation episode (SpO2 below 95%) was also noted.

Statistical analysis

Sample size was calculated taking the incidence of emergence delirium in the pediatric population receiving general anesthesia to be 18%, confidence limit to be 95%, power of study as 80%, and contingency factor to be 10%. Data were analyzed using the Statistical Package for the Social Science software (version 15.0, Chicago, Illinois) and were expressed as number (n), percentage, mean ± standard deviation (SD), or median as appropriate. Student t-test was used to compare the mean value of quantitative data such as age, weight, time to achieve hemostasis, duration of surgery, and time to recovery between the two groups. Two-way repeated-measures analysis of variance was used for intergroup comparison of MBP and HR. Nonparametric data such as RSS, PAED scale score, and VAS score were compared between groups with Mann–Whitney U-test. Fisher's exact test was used for comparison of gender; incidence of obstructive sleep apnea in each group and number of patients requiring rescue analgesia. P < 0.05 was considered statistically significant.

RESULTS

The two groups were comparable with respect to patient's age, sex, weight, history of obstructive sleep apnea, baseline HR, and MBP. None of our patients in either group had a history of OSAS [Table 1]. Dexmedetomidine was well tolerated, and no drug-related adverse events were observed. There were no episodes of bradycardia or hypotension in both the groups. Time to achieve hemostasis was comparable in both the groups (P = 0.673), but statistically significant difference was observed between two groups with regard to duration of surgery (P = 0.005) and time to extubation (P = 0.001) [Table 2]. Significant difference between HR and MBP was also found at all the readings, namely, postintubation, preincision, and every 5 min’ readings till the end of 30-min postincision (P < 0.05). The PAED scale score (mean ± SD) in Group D was statistically lower in Group D compared to Group C (13.84 ± 1.39; median 14 in Group C vs. 9.37 ± 1.33; median 9.5 in Group D; P < 0.001). While all patients in Group C had PAED scale score >12, only 2 (6.67%) patients in Group D had PAED scale score = 12. The patients in Group D had higher RSS in PACU compared to Group C (2.62 ± 0.49 in Group D vs. 1.60 ± 0.50, P = 0.004); none of the patients were excessively sedated or had RSS >3. No significant difference was found in VAS score of the groups at all times, except at 0 h (P = 0.002). None of the patients in both the groups had VAS score >3 at any time, so none of them required rescue analgesia. No episodes of desaturation (SpO2 below 95%) could be detected in both groups.

Table 1

Demographic profile of patients

	Group C (n=30)	Group D (n=30)	P
Age (years)	7.9±1.4	7.7±1.4	0.578
Sex (male: female)	23:7	20:10	0.567
Weight (kg)	23.2±4.0	22.2±4.3	0.355
Patient with OSAS (n)	0	0	-
Baseline HR (beats/min)	115.30±4.87	110.87±6.23	0.325
Baseline MBP (mmHg)	73.93±3.12	74.53±3.05	0.454

Data are expressed as n and mean±SD. Group C=Control group, Group D=Dexmedetomidine group, OSAS=Obstructive sleep apnea syndrome, HR=Heart rate, MBP=Mean blood pressure, SD=Standard deviation

Table 2

Intraoperative and immediate postoperative parameters

	Group C (n=30)	Group D (n=30)	P
Postintubation HR	127.60±4.43	112.33±5.72	<0.001*
Preincision HR	117.83±4.15	102.50±5.46	0.037*
HR 30 min after incision	131.67±2.80	97.90±2.48	<0.001*
Postintubation MBP	86.03±2.33	76.53±2.76	<0.001*
Preincision MBP	84.03±2.41	74.53±2.76	<0.001*
MBP 30 min after incision	85.37±3.19	76.27±2.64	0.042*
Time to achieve hemostasis (min)	11.13±2.36	7.53±1.87	0.673
Duration of surgery (min)	35.90±3.58	26.33±2.64	0.005*
Time to extubation (min)	5.23±1.91	7.70±1.62	0.001*
PAED scale score (median)	13.84±1.39 (14)	9.37±1.33 (9.5)	<0.001*
Ramsay sedation score	1.60±0.50	2.62±0.49	0.004*
VAS at 0 h	1.91±0.68	1.23±0.62	0.002*

*P<0.05. Data are expressed as n and mean±SD. Group C=Control group, Group D=Dexmedetomidine group, HR=Heart rate, MBP=Mean blood pressure, PAED=Paediatric Anesthesia Emergence Delirium, VAS=Visual analog scale, SD=Standard deviation

DISCUSSION

Single preoperative dexmedetomidine infusion at the dose of 1 μg/kg resulted in predictable and stable hemodynamic response of significantly lower HR and MBP, as compared to control group, without causing bradycardia or hypotension in any of the patients in Group D and did not warrant any corrective action. None of the patients in our study had a history of OSAS though the prevalence rate of 2% is reported in this age group.[11] This can be explained by thin habitus of the patients, unawareness, and nonreliable history of the parents regarding OSAS or small population size of the patients. Single preoperative dexmedetomidine infusion at the dose of 1 μg/kg resulted in predictable and stable hemodynamic response of significantly lower HR and MBP, as compared to control group, without causing bradycardia or hypotension in any of the patients in Group D and did not warrant any corrective action. Dexmedetomidine is known to cause dose-dependent decrease in HR and MBP, by decreasing the sympathetic activity, resulting from postsynaptic activation of α-2 adrenoceptors, by decreasing the circulating catecholamine levels and also by augmenting the cardiovagal activity.[12] Avoiding an initial loading dose of dexmedetomidine or its slow infusion over 10 min attenuates the severity of the hypotension and bradycardia, while larger doses of dexmedetomidine (2–3 μg/kg/h) cause more profound hemodynamic changes.[131415] Children of younger age, infants, those taking β-blockers or any drugs, that lower HR, and those with congenital heart disease and cardiac conduction defects are particularly susceptible.[14]

Duration of surgery was significantly lower in Group D (26.33 ± 2.64 min in Group D vs. 35.90 ± 3.58 min in Group C, P = 0.005), which can be attributed to blunted physiological response and controlled hypotension caused by dexmedetomidine, leading to decrease surgical bleed.

Ideally, the anesthetic-sparing effect of dexmedetomidine should have facilitated earlier awakening and tracheal extubation, but in the present study, time to tracheal extubation was significantly longer in Group D (P = 0.001). Similar findings were reported by Guler et al., who, in their study, found that a single dose of 0.5 μg/kg dexmedetomidine, 5 min before the end of surgery significantly prolonged time to emergence and extubation (P < 0.05) in comparison with placebo in patients undergoing adenotonsillectomy.[16] This may be attributable to residual sedation in Group D patients as indicated by their higher RSS in PACU because of shorter duration of adenotonsillectomy procedure, elimination half-life of dexmedetomidine being 1.8–2 h.[13]

Presynaptic activation of α-2 adrenoceptors in the locus coeruleus by dexmedetomidine inhibits noradrenaline release and induces sedation, which closely mimics natural nonrapid eye movement sleep.[17] In this study, though RSS was significantly higher in Group D, none of the patients were excessively sedated or had RSS >3, implying single dose of 1 μg/kg dexmedetomidine can produce a desirable kind of sedation in children.

EA is a common problem seen in these groups of patients, with reported incidence ranging from 2% to 80%.[818] During motor agitation, children risk themselves by dislodging intravenous tubing, dressings or drains, bleeding from operative site, and increasing their pain, which can be terrorizing to parents. In a meta-analysis of published articles, Dahmani et al. observed that out of various pharmacological agents given to prevent EA, namely, propofol given at the end of surgery; intraoperative fentanyl; and ketamine, premedication by clonidine, dexmedetomidine, hydroxyzine, midazolam, melatonin; clonidine, dexmedetomidine, and melatonin were found to be effective.[18] In this study too, dexmedetomidine group had significantly lower PAED scale score compared to placebo group. While all patients in Group C had PAED scale score >12, only 2 (6.67%) patients in Group D had PAED scale score = 12, suggesting the role of dexmedetomidine in decreasing the incidence and severity of EA.[19] This seems to be dose dependent as dexmedetomidine dose of 1 μg/kg iv reduces the incidence of EA by 90% whereas an infusion of 0.2 μg/kg/h reduces the incidence of agitation by 60%.[2021] Intranasal and oral administration of dexmedetomidine at doses of 1–4 have also been proven to decrease the incidence of parenteral separation anxiety, analgesic requirement, and postoperative EA.[222324]

Dexmedetomidine produces analgesic- and opioid-sparing effect by stimulating α-2 receptors in locus coerulus and dorsal horn, leading to termination of nociceptive signals. In this study, postoperative VAS scores for pain, though not statistically significant (except at 0 h, P = 0.002), it was always lower in Group D, as compared to Group C. Patel et al., in their study, also found that in children with obstructive sleep apnea undergoing tonsillectomy and adenoidectomy, intraoperative dexmedetomidine decreased the postoperative pain scores, and the number of rescue doses of morphine, in comparison with fentanyl.[7] Guler et al. also found that 23% of patients who received a single dose of 0.5 μg/kg dexmedetomidine before the end of the procedure required rescue analgesia in the PACU in comparison with 53% in the placebo group.[16] In the present study, none of the patients in either group required rescue analgesia, which may be because of the use of iv tramadol in the immediate postoperative period.

None of the patients in either group encountered any episodes of desaturation (SpO2 below 95%) in the PACU. Till date, dexmedetomidine has not been reported to affect the central respiratory centers, thus eliminating any direct risk of apnea or respiratory depression, making it a safe alternative for use, for sedation, and analgesia in patients with OSAS.

CONCLUSION

A preinduction single-dose intravenous infusion of dexmedetomidine at the dose of 1 μg/kg in children undergoing adenotonsillectomy provided better intraoperative hemodynamics and postoperative pain scores, when compared to placebo. Although it leads to increase in time to extubation, dexmedetomidine use significantly decreased postoperative EA score. No episodes of excessive sedation, desaturation, or any other drug-related adverse events such as hypotension or bradycardia were observed. Hence, to conclude, dexmedetomidine is a useful anesthetic adjunct to reduce postoperative EA and analgesic requirement without causing any cardiorespiratory impairment.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.