What are the recommended doses for dexmedetomidine and dexamethasone for adjuvant as caudal anesthesia in pediatric patients?

Comment by InpharmD Researcher

The commonly recommended dose for dexmedetomidine as a caudal adjuvant in pediatric patients is 1 to 2 mcg/kg, while dexamethasone is typically administered at 0.1 mg/kg. Both adjuvants have shown efficacy in extending the duration of analgesia for caudal blocks in pediatric patients without significant postoperative complications. However, given the off-label status of caudal dexmedetomidine and dexamethasone, additional high-quality randomized controlled trials are needed to further assess safety and potential delayed neurological complications. Only one randomized study evaluated dexmedetomidine 1 mcg/kg plus dexamethasone 0.1 mg/kg plus bupivacaine for caudal blocks in pediatrics; the combination was found to as effective as dexamethasone plus bupivacaine and dexmedetomidine plus bupivacaine with no significant differences in adverse effects.

Background

The 2018 European Society of Regional Anaesthesia and Pain Therapy (ESRA) and the American Society of Regional Anesthesia and Pain Medicine (ASRA) developed a joint committee practice advisory on local anesthetics (LAs) and adjuvants dosage in pediatric regional anesthesia. While the panel did not provide a recommendation for a specific dose, it was stated that dexmedetomidine has been employed to extend postoperative analgesia when utilized alongside neuraxial blocks (i.e., caudal block). However, due to the scarcity of toxicity data in children, it is advisable to administer the minimum effective dose to attain the desired benefits while mitigating potential adverse effects (Evidence A2). Corticosteroids, such as dexamethasone, have been examined in limited studies as a neuraxial adjuvant in pediatric patients. According to the available clinical evidence at the time of the publication of this guideline, the advisory committee does not endorse the utilization of corticosteroids as a neuraxial adjuvant in children (Evidence B2). [1]

A 2022 network meta-analysis (NMA) compared the safety and efficacy of caudal adjuvants in pediatric lower abdominal and urological surgeries. The final analysis included 112 randomized controlled trials (RCTs) involving 6,800 pediatric patients. Ten adjuvants were evaluated: clonidine, dexamethasone, dexmedetomidine, fentanyl, ketamine, magnesium, midazolam, morphine, neostigmine, and tramadol. Neostigmine, dexmedetomidine, and dexamethasone were the three most effective adjuvants for prolonging the duration of analgesia for caudal block, extending the duration by 8.9 hours (95% confidence interval [CI] 7.1 to 10.7 hours), 7.3 hours (95% CI 6.0 to 8.6 hours), and 5.9 hours (95% CI 4.0 to 7.7 hours), respectively. Dexmedetomidine dosage ranged from 0.5 mcg/kg to 2 mcg/kg with 1 to 2 mcg/kg as the most reported dose. The dosing of 1 to 2 mcg/kg have been indicated as effective in multiple review articles. The hemodynamic effects, particularly bradycardia, were infrequent and primarily associated with the 2 mcg/kg. [2], [3]

All included studies reported a dexamethasone dosage of 0.1 mg/kg. Dexmedetomidine and dexamethasone showed no postoperative complications such as nausea and vomiting. These findings suggest that dexmedetomidine and dexamethasone may be the most beneficial adjuvants to add to LAs for caudal block in children. However, further high-quality RCTs are warranted, especially to determine whether delayed neurological complications will occur, given the off-label status of caudal dexmedetomidine and dexamethasone. [2]

Another 2022 NMA, aimed to assess the comparative analgesic effectiveness and ranking of caudal adjuvants when added to LAs in pediatric infraumbilical surgery. The analysis included a total of 5,285 participants across 87 RCTs. Nine caudal adjuvants, namely clonidine, dexmedetomidine, ketamine, magnesium, morphine, fentanyl, tramadol, dexamethasone, and neostigmine, were compared among themselves or to a control group with no adjuvant. According to the treatment rankings and the surface under the cumulative ranking curve (SUCRA), neostigmine emerged as the most effective adjuvant, followed by tramadol and dexmedetomidine. In comparison to the control group, dexmedetomidine demonstrated a significant reduction in the frequency of analgesic dose administration within 24 hours (29 RCTs, 1,765 patients; weighted mean difference [WMD] -1.2 dose, 95% CI -1.6 to -0.9) and the total dose of acetaminophen within the same time frame (18 RCTs, 1,156 patients; WMD -350 mg, 95% CI -467 to -232). Dexmedetomidine was administered at doses ranging from 1 mcg/kg to 2 mcg/kg, while dexamethasone dosing was set at 0.1 mg/kg. Among the caudal adjuvants, neostigmine (with moderate certainty), tramadol (with low certainty), and dexmedetomidine (with low certainty) exhibited the most prolonged duration of analgesia. Dexmedetomidine, with moderate certainty, also outperformed other caudal adjuvants in reducing analgesic frequency and consumption. Caution is warranted in interpreting these findings due to variations in demographics, differences in local anesthetics and adjuvant doses, potential biases in the source trials, and the limitations of small study sizes. [4]

In a meta-analysis conducted in 2018, the investigation focused on the use of dexamethasone as an adjuvant in caudal blockade for pediatric patients. The analysis included 14 RCTs with a total of 1,315 pediatric patients, primarily undergoing lower abdominal operations such as orchidopexy, inguinal hernia repair, and hypospadias repair. The caudal dose of dexamethasone ranged from 0.1 to 0.2 mg/kg, while intravenous (IV) administration varied from 0.5 to 1.5 mg/kg, typically up to 10 mg. Dexamethasone demonstrated a significant extension in the duration of analgesia for both caudal (5.43 hours, 95% CI 3.52 to 7.35; p <0.001; I2 = 99.3%) and intravenous routes (5.51 hours; 95% CI 3.56 to 7.46; p <0.001; I2 = 98.9%) compared to the control group. Moreover, it led to a reduction in the need for narcotic rescue analgesia in the postanesthetic care unit (relative risk [RR] 0.30; 95% CI 0.18 to 0.51; p <0.001; I2 = 0.0%), diminished subsequent postoperative rescue analgesia requirement (RR 0.46; 95% CI 0.23 to 0.92; p = 0.03; I2 = 96.0%), and lower incidence of postoperative nausea and vomiting (RR 0.47; 95% CI 0.30 to 0.73; p = 0.001; I2 = 0.0%). Rare adverse events were associated with dexamethasone. The findings suggest that both caudal and intravenous administration of dexamethasone are comparably effective in extending the duration of analgesia in caudal blockade, resulting in a doubled to tripled duration. Considering the off-label status of caudal dexamethasone, intravenous administration is recommended, although the studies have primarily investigated higher intravenous doses (0.5 mg/kg up to 10 mg). [5]

References:

[1] Suresh S, Ecoffey C, Bosenberg A, et al. The European Society of Regional Anaesthesia and Pain Therapy/American Society of Regional Anesthesia and Pain Medicine Recommendations on Local Anesthetics and Adjuvants Dosage in Pediatric Regional Anesthesia. Reg Anesth Pain Med. 2018;43(2):211-216. doi:10.1097/AAP.0000000000000702
[2] Xiong C, Han C, Lv H, et al. Comparison of adjuvant pharmaceuticals for caudal block in pediatric lower abdominal and urological surgeries: A network meta-analysis. J Clin Anesth. 2022;81:110907. doi:10.1016/j.jclinane.2022.110907
[3] Wiegele M, Marhofer P, Lönnqvist PA. Caudal epidural blocks in pediatric patients: a review and practical considerations. Br J Anaesth. 2019;122(4):509-517. doi:10.1016/j.bja.2018.11.030
[4] Shah UJ, Karuppiah N, Karapetyan H, Martin J, Sehmbi H. Analgesic Efficacy of Adjuvant Medications in the Pediatric Caudal Block for Infraumbilical Surgery: A Network Meta-Analysis of Randomized Controlled Trials. Cureus. 2022;14(8):e28582. Published 2022 Aug 30. doi:10.7759/cureus.28582
[5] Chong MA, Szoke DJ, Berbenetz NM, Lin C. Dexamethasone as an Adjuvant for Caudal Blockade in Pediatric Surgical Patients: A Systematic Review and Meta-analysis. Anesth Analg. 2018;127(2):520-528. doi:10.1213/ANE.0000000000003346

Literature Review

A search of the published medical literature revealed 2 studies investigating the researchable question:

What are the recommended doses for dexmedetomidine and dexamethasone for adjuvant as caudal anesthesia in pediatric patients?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→



Please see Tables 1-2 for your response.


 

Caudal Analgesia for Hypospadias in Pediatrics: Comparative Evaluation of Adjuvants Dexamethasone and Dexmedetomidine Combination versus Dexamethasone or Dexmedetomidine to Bupivacaine: A Prospective, Double-Blinded, Randomized Comparative Study

Design

Randomized, double-blind, single-center, controlled trial

N= 63

Objective

To compare the combination of dexamethasone and dexmedetomidine as adjuvants to bupivacaine versus using each agent solely with bupivacaine in pediatric caudal block as regards their efficiency in pain relief

Study Groups

Dexamethasone (n= 21)

Dexmedetomidine (n= 21)

Dexamethasone + dexmedetomidine (n= 21)

Inclusion Criteria

Children aged 1-6 years scheduled for hypospadias surgery; Anesthesiologists Physical Status Classes I or II

Exclusion Criteria

Contraindication to caudal anesthesia (e.g., coagulopathy, spinal deformation); cardiovascular disease; type I diabetes mellitus; allergy to any study medication

Methods

Children scheduled to undergo hypospadias surgery at an Egyptian hospital were randomized to one of three groups for caudal anesthesia: dexamethasone 0.1 mg/kg + 0.5 mg/kg bupivacaine 0.25%; dexmedetomidine 0.01 μg/kg + 0.5 mg/kg bupivacaine 0.25%; or dexamethasone 0.1 mg/kg + dexmedetomidine 0.01 μg/kg + 0.5 mg/kg bupivacaine 0.25%.

All patients received general anesthesia via inhaled sevoflurane 6% with 100% oxygen followed by orotracheal intubation and maintenance by spontaneous ventilation with 100% O2 at 2% sevoflurane. The patients were then tilted on their lateral side and caudal anesthesia was administered using a 5-cm short-beveled 22-gauge needle with the loss of resistance technique; the injection was done after aspiration to exclude intravascular injection.

Fifteen minutes after the caudal block, the procedure started. Bradycardia was treated with atropine 0.02 mg/kg and hypotension was treated with IV fluids plus ephedrine 5 mg/kg. After surgery completion, the volatile anesthesia was stopped and the patients were extubated when adequate spontaneous ventilation was established. Patients were then transferred to the recovery room and the postoperative anesthesia care unit (PACU) for discharge.

Pain scores were assessed in the PACU at 30 min, 1, 2, 3, 6, and 12 h. Post-operative analgesia involved IV acetaminophen 15 mg/kg if the pain scores were >4.

Duration

December 2015 to February 2017

Outcome Measures

Primary: time to first request of analgesia; pain scores

Secondary: hemodynamic variables, sedation scores, adverse effects

Baseline Characteristics

  Dexamethasone (n= 21) Dexmedetomidine (n= 21) Dexamethasone + dexmedetomidine (n= 21) p-value
Age, years  4.4 ± 2.5 4.1 ± 2.3 4.3 ± 2.3

0.946

Weight, kg

17.9 ± 5.4 21 ± 7.7 17.8 ± 5.5 0.31

Surgery duration, h

2 ± 0.4 2 ± 0.6 2 ± 0.5 0.705

Results

  Dexamethasone (n= 21) Dexmedetomidine (n= 21) Dexamethasone + dexmedetomidine (n= 21) p-value

Time to first analgesia, h

4.5 ± 2.8 7.4 ± 1.5 11.3 ± 3.5 0.001

Heart rate, beats/min

Baseline

At induction

After 30 minutes

After surgery

 

139.2 ± 17.5

127.3 ± 20

110.9 ± 23

112.8 ± 20

 

138.2 ± 19

132.4 ± 21

119.7 ± 16

116.5 ± 14

 

138.2 ± 15

125 ± 13

104.8 ± 14

116.5 ± 14

 

1

0.93

0.098

1

Mean arterial pressure, mmHg

Baseline

At induction

After 30 minutes

After surgery

 

66.6 ± 9

58.9 ± 8

59.1 ± 10

64.3 ± 7.3

 

62.4 ± 10.6

54.2 ± 8.9

51.9 ± 6.5

53.2 ± 6.2

 

62.5 ± 9.2

58.2 ± 5.6

50.1 ± 8.2

54 ± 8.3

 

0.76

0.416

0.017

0.000

There was a significant reduction in pain score in the combination group compared to the other two groups at 30 min, 1, 2, and 6 h postoperatively (p< 0.01 for each time point). The pain scores increased in the combination group more than the other two at 12 h postoperatively with the start of the first request of analgesics; however, there was no statistically significant difference (p= 0.2).

Adverse Events

Postoperative bradycardia was seen in 1 patient who received dexamethasone/dexmedetomidine combination compared to 2 patients in each of the other groups (p= 0.79).

Hypotension was seen in 2 patients in the dexmedetomidine group, 1 patient in the dexamethasone/dexmedetomidine combination group, and none in the dexamethasone group (p= 0.34)

Nausea/vomiting was only experienced by 2 patients who received dexamethasone. No patients experienced respiratory depression.

Study Author Conclusions

The addition of combined dexmedetomidine at a dose of 1 μg/kg and dexamethasone 0.1 mg/kg to caudal bupivacaine seemed to be an attractive alternative to each drug if used alone with more prolonged analgesia and almost no adverse effects.

InpharmD Researcher Critique

This study is limited by the single-center (in Egypt) setting and small sample size of young, healthy children undergoing lower abdominal surgery. Another limitation is the short follow-up of 12 hours. The co-primary endpoint of pain score was confounded by postoperative analgesia use. 



References:

Hassan PF, Hassan AS, Elmetwally SA. Caudal Analgesia for Hypospadias in Pediatrics: Comparative Evaluation of Adjuvants Dexamethasone and Dexmedetomidine Combination versus Dexamethasone or Dexmedetomidine to Bupivacaine: A Prospective, Double-Blinded, Randomized Comparative Study. Anesth Essays Res. 2018;12(3):644-650. doi:10.4103/aer.AER_77_18

 

Nonopioid (Dexmedetomidine, Dexamethasone, Magnesium) Adjuvant to Ropivacaine Caudal Anesthesia in Pediatric Patients Undergoing Infraumbilical Surgeries: A Comparative Study

Design

Randomized, prospective, comparative cohort study

N= 128

Objective

To analyze the efficacy of adjuvants dexmedetomidine, dexamethasone, and magnesium as an adjuvant to ropivacaine in caudal analgesia in pediatric infraumbilical surgeries in terms of duration of postoperative analgesia, postoperative sedation, intraoperative hemodynamics, and postoperative side effects

Study Groups

Control (0.5 mL/kg of injection ropivacaine 0.2% + 0.9% normal saline) (n= 32)

0.5 mL/kg of injection ropivacaine 0.2% + dexmedetomidine 1 mcg/kg (n = 32)

0.5 mL/kg of injection ropivacaine 0.2% + dexamethasone 0.1 mg/kg (n = 32)

0.5 mL/kg of injection ropivacaine 0.2% + magnesium sulfate 50 mg (n = 32)

Inclusion Criteria

Patients with physical status American Society of Anesthesiologists (ASA) Classes I and II, aged 3–12 years, scheduled for infraumbilical surgeries

Exclusion Criteria

Patients with contraindications to caudal anesthesia, cardiovascular diseases, drug allergy, and coagulation disorders, or those whose families did not approve inclusion in the study

Methods

Eligible patients were randomly assigned to receive normal saline, dexmedetomidine 1 mcg/kg, dexamethasone 0.1 mg/kg, or magnesium sulfate 50 mg with injection ropivacaine 0.2% in the dose 0.5 mL/kg causally. The surgical procedure commenced at least 10 minutes after the caudal block. The block was deemed unsuccessful if there was a 15% change in heart rate (HR) or mean arterial blood pressure (MAP) from the baseline, resulting in the exclusion of the patient from the study. In such cases, intravenous (IV) fentanyl (1 mcg/kg) was administered to ensure analgesia.


In the postoperative anesthesia care unit (PACU), evaluations of the Modified Objective Pain Score (MOPS) and Ramsay Sedation Score (RSS) were conducted at 30 minutes, 1, 2, 3, 6, and 12 hours. When the MOPS exceeds 4, the patient is administered additional analgesia in the form of IV paracetamol injection at a dosage of 15 mg/kg as rescue analgesia.

Duration

December 2015 to August 2016

Outcome Measures

MOPS, RSS, duration of analgesia, hemodynamic changes, and side effects

Baseline Characteristics

  Control

Dexmedetomidine

Dexamethasone

Magnesium   

Age, years

5.44 ± 2.54  6.09 ± 3.90  6.16 ± 3.00 6.28 ± 3.67  

Weight, kg

17.38 ± 6.29 18.16 ± 8.63  19.09 ± 8.18 19.28 ± 8.97  

Female

34.4% 12.5% 15.6% 12.5%  

Duration of surgery, min

105.1 ± 11.6  101.4 ± 9.8  103.3 ± 9.7 111.2 ± 10.1  

Results

Endpoint

Control

Dexmedetomidine

Dexamethasone 

Magnesium

p-value

Median MOPS

30 min

1 h

2 h

3 h

6 h

12 h

 

2.0 (0.0-3.0)

2.0 (1-3)

2.0 (1.25-3.0)

2.0 (2.0-3.0)

4.0 (2-4.0)

4.0 (2.0-4.75) 

 

2.0 (1.0-2.0)

2.0 (1.0-2.0)

1.5 (1.0-2.0)

2.0 (1.0-2.0)

1.50 (1.0-20)

1.0 (1.0-2.0) 

 

1.0 (0-2)

1.0 (0.2-2)

1.0 (1-2)

1.0 (1-2)

1.0 (1-2)

1.0 (1-2) 

 

2.0 (2-3)

2.0 (2-3)

2.0 (2-3)

2.0 (2-3)

2.0 (2-3)

2.0 (1.0-3.8) 

 

0.312

0.359

0.954

0.102

≤0.01

≤0.05

Median RSS

30 min

1 h

2 h

3 h

6 h

12 h

 

2.0 (2-2)

2.0 (2-2)

2.0 (1-2)

1.5 (1-2)

1.0 (1-2)

2.0 (1-2) 

 

3.5 (3-4)

3.0 (3-4)

3.0 (3-3.75)

2.5 (2-3)

2.0 (2-2)

2.0 (2-2) 

 

2.0 (2-2)

2.0 (2-2)

2.0 (1-2)

2.0 (1-2)

2.0 (1-2)

2.0 (1-2) 

 

2.0 (1.0-2.75) 

2.0 (1.0-2.0)

2.0 (1-2)

2.0 (1-2)

2.0 (1-2)

1.5 (1.0-2.0

 

0.306

0.118

0.621

0.319

0.111

0.971 

Rescue time, min 285.94 ± 52.78 406.25 ± 45.49 450.00 ± 72.60 325.00 ± 45.79 <0.001

The following were presented as figures from which precise data was unretrievable:

  • The means of HR changes among the studied groups were comparable at all times monitored.
  • The means of MAP changes among the studied groups were comparable at all times. 

Adverse Events

No adverse effect was noted in any of the groups.

Study Author Conclusions

The caudal adjuvants used in the current study, dexmedetomidine 1 mcg/kg, dexamethasone 0.1 mg/kg, and magnesium 50 mg added to 0.2% ropivacaine, provide and prolong the postoperative analgesia in pediatric infraumbilical surgeries without undue sedation and adverse effects.

InpharmD Researcher Critique

The study on caudal analgesia and adjuvants, though insightful, has limitations. Concerns include potential systemic effects, especially with neuraxial administration of dexmedetomidine and dexamethasone, contrasting with higher intravenous doses in other studies. Lack of monitoring for dexamethasone-related adverse effects and dosages based on previous studies are noted limitations. The absence of immediate adverse events is reported, but a more detailed assessment is needed. Extending the observation period could reveal late-onset effects or prolonged differences in analgesic duration. 



References:

Sridhar RB, Kalappa S, Nagappa S. Nonopioid (Dexmedetomidine, Dexamethasone, Magnesium) Adjuvant to Ropivacaine Caudal Anesthesia in Pediatric Patients Undergoing Infraumbilical Surgeries: A Comparative Study. Anesth Essays Res. 2017;11(3):636-641. doi:10.4103/0259-1162.206853