Study reference

Study characteristics

Patient characteristics

Intervention (I)

Comparison / control (C)

Follow-up

Outcome measures and effect size

Comments

Akbas 2005

Type of study: RCT

Setting and country: Single-centre, Turkey

Funding and conflicts of interest: Not reported.

Inclusion criteria: ASA physical status I–II, age 2–12 years scheduled for inguinal hernia repair and circumcision were randomly allocated into three study groups

Exclusion criteria: Children for whom there was contraindication to caudal block were excluded from the study.

N total at baseline:

I: 25

C: 25

Important prognostic factors²:

Mean age (years) ± SD:

I: 6.08 ± 2.87

C: 5.64 ± 3.13

Weight; mean ± SD:

I: 20.34 ± 8.27
C: 18.96 ± 8.55

Groups comparable at baseline?

There were no significant differences among the three study groups with respect to age, weight or

duration of surgery.

ropivacaine 0.2% 0.75 mlÆkg)1

plus clonidine 1 lgÆkg) (group RC)*

received ropivacaine 0.2%, 0.75 mlÆkg) (group R)*

*Drugs were diluted in 0.9% saline (0.75 mlÆkg)1)

Length of follow-up:

POD1

Loss-to-follow-up:

Not reported.

Incomplete outcome data:

Not reported, data seems complete for both groups as indicated by n in all tables.

1.Postoperative pain

Oucher Pain Scale; scores greater than 60 were assessed as pain.

This is an observational pain scoring system using five criteria: crying, agitation, movement, posture and localization of pain. Each criterion scores 0–2 to give a total score of 0–10

1.1. PACU

1.2. 6 hours

1.3. 24 hours

“There were no statistically significant differences

among the groups with respect to Oucher’s Pain Scale and modified OPS”

3. Postoperative opioid consumption

Scores greater than 60 were

assessed as pain and this time was recorded and

supplementary analgesic given in the ward or in the

house by parents (paracetamol 15 mgÆkg)1 orally).

3.3. Total

Total number of analgesic requirement

I: 4
C: 6

4. Adverse events

4.2. Respiratory depression

decrease in SpO2 <95% requiring supplementary oxygen

“No episode of SpO2 was detected.”

I: 0
C: 0

4.3. Hypotension

 An intraoperative decrease in SBP of more

than 30% from preoperative values

Under a figure it was reported there were “no significant differences” in SBP. / “There were no incidents of hypotension”.

I: 0
C: 0

4.4. Sedation

A three-point sedation scale (1, awake; 2, asleep but arousable by verbal contact; 3, asleep and not arousable by verbal contact)

“sedation scores were higher in group RC for the first 1-h period after the operation than the other groups”

Study aim: to compare the analgesic

quality and duration of ropivacaine 0.2% with the addition of

clonidine (1 lgÆkg)1

) with that of ropivacaine 0.2% and the addition of

ketamine (0.5 mgÆkg)1

) to that of ropivacaine 0.2% and also compare

the postoperative cortisol, insulin and glucose concentrations,

sampled after induction and 1 h later following caudal administration

in children

Akin, 2010

Type of study: RCT

Setting and country: single-centre, Turkey

Funding and conflicts of interest: not reported

Inclusion criteria: children aged 2–8 , ASA I–II, undergoing elective

inguinal hernia repair or orchidopexy surgery

Exclusion criteria: contraindication to caudal block or the study drugs

N total at baseline:

I1: 20

12: 20

C: 20

Important prognostic factors²:

For example

age ± SD:

I1: 4.1 ± 2

12: 4.1 ± 2

C: 4.1 ± 2

Weight:

I1: 17.0 ± 4.6

12: 17.4 ± 6.5

C: 17.7 ± 5.3

Surgical duration (min):

I1: 34.4 ± 12.5

12: 27.0 ± 9.5

C: 32.8 ± 12.6

Groups comparable at baseline? Age,

weight and the duration of surgery were similar

among the three study groups

I1: Levobupivacaine 0.25% 0.75 mlÆkg)1 and 2 lgÆkg)1 clonidine caudally and 5 ml normal saline i.v. (Group L-Ccau)

I2: Levobupivacaine 0.25%, 0.75 mlÆkg)1 and 2 lgÆkg)1 clonidine in 5 ml normal saline i.v. (Group L-Civ)

Levobupivacaine 0.25% 0.75 mlÆkg)1 and 5 ml normal saline i.v (group L)

Length of follow-up:

24 h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported, data seems complete for both groups as indicated by n in all tables.

1.Postoperative pain

Children and

Infants Postoperative Pain Scale (CHIPPS)

1.1. PACU

1.2. 6 hours

1.3. 24 hours

Results provided in a figure not readable à control group higher pain scores first hour but similar at 6 hours and 24 hours.

3. Postoperative opioid consumption

Patients with a CHIPPS score ≥4 were given

Tramadol oral drops (2 mgÆkg)1)

3.3. Total

N requiring rescue analgesia in the first 24 h postoperatively

I1: 19 of 20

12: 13 of 20

C: 17 of 20

4. Adverse events

4.2. Respiratory depression

“no episodes of SpO2 was recorded.”

I: 0
C: 0

4.3. Hypotension

Hypotension was defined as a

20% decrease in systolic blood pressure when compared with baseline.

“No incidents of hypotension were seen in any of the children studied”

I: 0
C: 0

4.4. Sedation

Ramsay Sedation

Score

“The mean

postoperative sedation score was higher in Group LCcau at 30, 60 and 240 min in postprocedure compared to Groups L and L-Civ but not at extubation, 15 and 120 min and 6, 12 and 24 h (P < 0.05, Figure 3).”

Study aim: to compare the

effects of caudal and intravenous (i.v.) clonidine on

postoperative analgesia after caudal levobupivacaine for inguinal herniorrhaphy or orchidopexy

surgery

Anouar, 2016

Type of study: RCT, double-blind

Setting and country: single-centre, Tunisia

Funding and conflicts of interest:

Inclusion criteria: ASA I (American society of anesthesiologists) unpremedicated children, aged from 1 to 5 years (µg20 kg) and undergoing day-case male circumcision

Exclusion criteria: allergy to local anesthetic, genital malformation, past history of penile surgery, preoperative incident and additional surgical procedure other than circumcision

N total at baseline:

I: 20

C: 20

Important prognostic factors²:

Age (months); mean ± SD:

I: 30 ±3.12

C: 25.2 ± 5

Weight (kg); mean ± SD:

I: 14.5 ± 1.5

C: 12.8 ± 2.1

Surgery duration (min); mean ± SD:

I: 16 ± 2.4
C: 17 ± 1.8

Groups comparable at baseline? Demographic parameters were similar in both groups

0.1 ml/Kg of bupivacaine 0.5% with 1µg/kg of clonidine in each side (group 1)

0.1 ml/kg of bupivacaine 0.5 % with placebo in each side (group 2)

Length of follow-up:

POD1

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported, data seems complete for both groups as indicated by n in all tables.

1.Postoperative pain

CHEOPS pain score

1.1.    PACU/ 0-h

I: 5.8 ± 0.9
C: 6.4 ± 0.8

1.2. 6 hours

I: 4.5 ± 0.5
C: 6.2 ± 1.1

1.3. 24 hours

I: 5.8 ± 0.9
C: 7.7 ± 0.4

3. Postoperative opioid consumption

3.1. PACU

Supplemental analgesia of intravenous nalbuphine

increments of 0.2 µg/Kg was provided if the CHEOPS pain score was >7

“no patient needed Nalbuphine in PACU.”

3.2. 24 hours/ 3.3. total

At home,

patients received oral paracetamol at the dose of 15mg/kg

systematically and Ibuprophene was given if CHEOPS (Children's

Hospital of Eastern Ontario Pain Scale) was superior to 7.

Number of patients

I: 5
C: 12

Study aim: to improve the DPNB analgesic effect by the adjunction of

clonidine as an adjuvant to bupivacaine 0.5% in this block.

Bajwa, 2010

Type of study: RCT; double-blind study

Setting and country: Single-centre, India

Funding and conflicts of interest: source of support: Nil; conflict of interest: none declared.

Inclusion criteria: ASA-I children, 1–9 years of age, scheduled for elective lower abdominal surgery (hernia surgery)

Exclusion criteria: local infection at the caudal region, bleeding diathesis, pre-existing neurologic or obvious spinal diseases, and any congenital anomaly of the lower back

N total at baseline:

I: 22

C: 22

Important prognostic factors²:

For example

Age (years); mean ± SD (range):

I: 3.4 ± 1.42 (1–9)

C: 3.1 ± 1.68 (1–9)

Sex (M/F); mean ± SD:

I: 20/2

C: 21/1

Weight (kg); mean ± SD:

I: 13.92 ± 6.16

C: 13.12 ± 7.86

Groups comparable at baseline? No difference could be detected from the data of 44 children regarding the patient demographics; The demographic profile of the patients in group I and group II was comparable with regards to age, weight and height and on statistical analysis no significant difference was found.

Group II (n = 22) received 0.25% ropivacaine, 0.5 ml/kg, with an addition of 2 µg/kg clonidine via the caudal route*

Group I (n = 22) received 0.25% ropivacaine, 0.5 ml/kg*

*with a total volume being constant at 0.5 ml/kg in both the study groups

Length of follow-up:

24 h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported, data seems complete for both groups as indicated by n in all tables.

1.Postoperative pain

A modified objective pain scale (OPS) was employed to assess the post-operative pain and duration of analgesia which was based on behavioural objectives that included crying, facial expressions, position of legs, position of torso and generalized motor restlessness. A score of 0 was considered as excellent analgesia while a score of 10 signifies completely ineffective analgesia.

Pain was recorded at a 10-min interval after extubation and thereafter at intervals of 1, 2, 4, 6, 8, 12, 18 and 24 h

1.3. 24 hours

Mean ± SD

I: 3.58 ± 0.40
C: 3.72 ± 0.42

3. Postoperative opioid consumption

3.1. PACU

3.2. 24 hours

3.3. Total

Not reported; Children who had a pain score of more than 4 were administered 15 mg/ kg of oral syrup of paracetamol.

4. Adverse events

4.2. Respiratory depression

I: 0

C: 0

4.4. Sedation

(opening of eyes: 3 = spontaneously, 2 = to verbal command, 1 = to physical shaking, 0 =not arousable)

Mean ± SD

I: 2.86 ± 0.52
C: 2.68 ± 0.56

Study aim: to determine qualitative and quantitative aspects of caudal block, haemodynamic

effects, and post-operative pain relief of ropivacaine 0.25% versus ropivacaine 0.25% with clonidine

for lower abdominal surgeries in paediatric patients

Bhati 2022

Type of study: RCT, double-blind

Setting and country: single-centre, India

Funding and conflicts of interest: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Inclusion criteria: American Society of Anaesthesiologists (ASA) physical status I, aged one to six years of both sexes, scheduled for infraumbilical elective surgery

Exclusion criteria: emergency surgery; known allergy to study drugs; known history of active renal, hepatic, respiratory, or cardiac disease; a history of seizures, neurological, or neuromuscular disorder; known or suspected coagulopathy, refusal, cutaneous local infection, or any congenital malformation.

N total at baseline:

I: 20

C: 20

Important prognostic factors²:

For example

age (years); mean ± SD:

I: 3.85 ± 1.39

C: 3.40 ± 1.31

Sex (%M):

I: 100%

C: 100%

Weight (kg):

I: 14.10 ± 2.77
C: 13.70 ± 4.03

Groups comparable at baseline? There was no statistically significant difference in the demographic profile of the patients, distribution of the type of procedure, and duration of surgery

group LC (n = 20) received caudal injection of 0.25% levobupivacaine at a dose of 1 mL/kg body weight with clonidine 0.5 µg/kg

group L (n = 20) received caudal injection of 0.25% levobupivacaine at a dose of 1 mL/kg body weight

Length of follow-up:

24h

Loss-to-follow-up:

Not after enrolment

Incomplete outcome data:

Intervention:

N (%)

Reasons (describe)

Control:

N (%)

Reasons (describe)

1.Postoperative pain

Hannallah pain scale

1.1.    PACU (arrival)

I: 0
C: 0

1.2.    6 hours

I: 0.75

C: 5

3. Postoperative opioid consumption

3.1. PACU

3.2. 24 hours

3.3. Total

Not reported; If the pain score was 4 or more, injection paracetamol 10 mg/kg was given as a rescue analgesic.

4. Adverse events

4.2. Respiratory depression

“No episodes of clinically significant postoperative complications such as nausea, vomiting, respiratory depression, urinary retention, and pruritis were observed in any of the patients.”

4.4. Sedation

Ramsay sedation scale; at PACU at arrival and then every hour

“Sedation score was 3 at 60 minutes post-block. All children were awake and alert 120 minutes post-block.”

Study aim: to compare the effect of dexmedetomidine and clonidine to accentuate the perioperative analgesia of 0.25% isobaric levobupivacaine in pediatric caudal anesthesia

De Mey, 2000

Type of study:

RCT (4 groups)

Setting and country: single centre, Belgium

Funding and conflicts of interest: not reported

Inclusion criteria: ASA class I or II boys, aged between 8 months and 13 years, admitted for hypospadias repair

Exclusion criteria:

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors²:

For example

Age (months) ± SD:

I: 39.1 ± 29.4

C: 38.3 ± 32.2

Weight:

I:  14.5 ± 5.6

C: 14.9 ± 6.9

Groups comparable at baseline? Age, weight, and duration of surgery were not significantly different in the four groups.

0.5 mL kg⁻¹ bupivacaine 0.25% caudally + 1 μg kg⁻¹ clonidine (group II)

0.5 mL kg⁻¹ bupivacaine 0.25% caudally (group I)

Length of follow-up:

24 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1.Postoperative pain

VAS (visual analog scale) in children older than 5 years and with CHEOPS (Children's Hospital of Eastern Ontario Pain Scale) in children less than 5 years of age

No absolute values reported, authors report that “The pain scores at 2, 4, 6, 8 and 12 h postoperatively were not significantly different among the four groups.”

3. Postoperative opioid consumption

Not reported, only paracetamol requirement

Study aim: to evaluate whether the addition of clonidine, or sufentanil, or both, to a bupivacaine solution for a caudal block prolonged the period of analgesia after operation in children.

De Negri, 2001

Type of study: randomized, observer-blinded study.

Setting and country: single-centre, Italy

Funding and conflicts of interest: not reported

Inclusion criteria: boys (age 1–4 yr,

ASA physical status I) scheduled to undergo inpatient

hypospadias repair

Exclusion criteria: commonly accepted contraindications to

epidural blockade and a history of allergic reactions to

local anesthetics.

N total at baseline:

Intervention: 15/15/15

Control: 15

Important prognostic factors²:

For example

Age (mo) ± SD:

I1: 31 ±10

I2: 28±14

I3: 32 ±9

C: 28 ± 12

Weight (kg) ± SD :

I1: 14 ± 5

I2: 13 ± 6

I3: 13 ± 5

C: 13 ± 7

Groups comparable at baseline? The four

groups were similar with respect to age, weight,

ASA physical status, baseline blood pressure and

heart rate, and time to eye opening after anesthesia

I1: ropivacaine 0.08% 0.16 mg · kg21 · h21 plus

clonidine 0.04mg · kg21 · h21 (Group RC1)

I2: ropivacaine

0.08% 0.16 mg · kg21 · h21 plus clonidine 0.08

mg · kg21 · h21 (Group RC2)

I3: ropivacaine 0.08%

0.16 mg · kg21 · h21 plus clonidine 0.12 mg · kg21 · h21

(Group RC3)

plain ropivacaine 0.1% 0.2 mg · kg21 · h21

(Group R)

Length of follow-up: postoperative 48-h period

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Three subjects in Group R and two subjects in

Group RC1 were excluded from the study because

of inadequate epidural block or catheter dislocation,

thus leaving 55 patients for final analysis.

1.Postoperative pain

Children’s

Hospital of Eastern Ontario Pain Score (CHEOPS)

(lowest score, 4, no pain; highest score, 13, severe pain)

CHEOPS scores

were lower in Group RC3 than RC2 than RC1 than

R;

2.Postoperative opioid consumption

Each child was prescribed

acetaminophen/codeine suppositories (200 mg/5 mg,

Lonarid; Boehringher, Ingel, Italy) (19) to be given by the

nurse if patients had CHEOPS scores .9 on two consecutive assessments 5min apart

2.3. Total number of doses of supplemental postoperative analgesics median (95% CI)

I1: 4 (2,6)

I2: 1 (2,6)

I3: 1 (0,3)

C: 4 (0,3)

4. Adverse events

4.4. Sedation

Presented in a figure not readable. Sedation scores for the first 48 postoperative hours. No statistical difference was found among the different study groups. The two

peaks in postoperative sedation coincide with the first and second postoperative night.

Study aim: to identify the dose response

relationship and possible side effects of

clonidine when added to a postoperative continuous epidural infusion of ropivacaine in children.

El-Hennway, 2009

Type of study: double-blinded RCT

Setting and country: single-centre, Egypt

Funding and conflicts of interest: not reported

Inclusion criteria: ASA status I and II patients,

aged 6 months to 6 yr undergoing lower abdominal surgeries

Exclusion criteria: a history of developmental

delay or mental retardation, which could make observational pain intensity assessment difficult; a known or suspected coagulopathy; a known allergy to any of the study drugs; and any signs of infection at the site of the proposed caudal block.

N total at baseline:

Intervention: 30

Control:30

Important prognostic factors²:

For example

age  months (range):

I: 45 (6–69)

C: 43 (7–66)

Weight (kg) (SD):

I: 16 (4.9)

C: 15 (4.4)

Groups comparable at baseline? subject characteristics and intraoperative

clinical profile were comparable among the three study groups

Group

‘B’ received: bupivacaine 0.25% (1 ml kg21) with clonidine 2 mg kg21 in normal saline 1 ml

Group ‘C’ received:

bupivacaine 0.25% (1 ml kg21) with normal saline 1 ml

Length of follow-up:

24 h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

observational FLACC pain scale

with its 0–10 score range

1.1.    PACU

I: score 0 (45%), score 1 (40%), score 2 (15%)

C: score 0 (25%), score 1 (45%), score 2 (30%)

1.2.    6 hours

Not reported

1.3. 24 hours

I: score 1 (30%), score 2 (40%), score 3 (30%)

C: score 1 (40%), score 2 (40%), score 2 (20%)

4. Adverse events

4.2. Respiratory depression

None observed

4.3. Hypotension

None observed 

Study aim: to compare the analgesic effects and

side-effects of dexmedetomidine and clonidine added to bupivacaine in pediatric patients undergoing lower abdominal surgeries.

Ivani, 2000

Type of study: prospective, observer-blinded RCT

Setting and country: single centre, Italy

Funding and conflicts of interest: not reported

Inclusion criteria: ASA 1 children, 1–7 years

of age, scheduled for elective sub-umbilical surgery

Exclusion criteria:

Not reported

N total at baseline:

Intervention: 20

Control: 20

Important prognostic factors²:

For example

Age (years) (range) [median (range)}

I: 3 (1–7)

C: 3 (1–7)

Sex (M/F):

I: 16/4

C: 18/2

Weight (kg) [median, range]:

I: 16 (10–22)
C: 16 (10–21)

Groups comparable at baseline? No difference could be detected between the two

groups regarding patient demographics (Table 1), intraoperative

HR, NIBP, RR, ETCO2 and SpO2 or in the

duration of surgery

Group R0.1C received

a caudal block with 1 ml/kg of ropivacaine

0.1% (Naropin, AstraZeneca, So¨derta¨lje, Sweden) with

the addition of clonidine 2 mg/kg (Catapress 150 mg/

ml, Boehringer-Ingelheim, Mannheim, Germany)

Group R0.2 received a caudal

block with 1 ml/kg of ropivacaine 0.2% (Naropin, AstraZeneca,

So¨derta¨lje, Sweden)

Length of follow-up:

24h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

modified

objective pain scale (OPS) score

1.1. PACU

1.2. 6 hours

1.3. 24 hours

The mean of the maximum OPS scores registered for each individual patient who did not require supplemental analgesia were similar between the R0.2 (1, range: 0–4) and the R0.1C (1, range: 0–4) groups (ns).

3. Postoperative opioid consumption

A fixed combination paracetamol

(350 mg)-codeine (15 mg) suppository (Citodon

Minor, AstraZeneca, So¨derta¨lje, Sweden), with the initial dosing based on paracetamol 40 mg/kg, was administered if the patient’s OPS score was >5.

3.1. PACU

Five patients

in the R0.2 group but no patients in the R0.1C group were given a paracetamol-codeine suppository within

3 h postoperatively.

3.2. 24 hours

3.3. Total

Significantly 2

4. Adverse events

4.4. Sedation [median, range]

four-point scale [0 (alert)–3

(not arousable)]

I: 1 (0–2)
C: 1 (0–1)

The duration of postoperative sedation was also found to be similar in the two groups (95 min; range 60–180 min and 90 min; range 60–190 min, in the R0.2 and R0.1C groups, respectively).

Study aim: to compare the analgesic efficacy

and adverse effects of clonidine and dexmedetomidine when combined with bupivacaine for caudal

analgesia in children undergoing infraumbilical surgeries

Jindal, 2011

Type of study: Prospective, randomized, double-blind study

Setting and country: single-centre, India

Funding and conflicts of interest: not reported

Inclusion criteria: American Society of

Anesthesiologists (ASA) physical status I and II children aged less than 2 years undergoing elective cleft lip repair under general anesthesia.

Exclusion criteria: Patients with local infection at the

site of injection of block, history suggestive of drug allergy, children with any systemic disease that compromises any

cardiovascular, respiratory or neurological function, any other congenital anomaly, patient with history of upper and

lower airway disease, coagulation disorders, and children with history of sleep apnea and in whom postoperative

ventilation may be required

N total at baseline:

Intervention: 25

Control: 25

Important prognostic factors²:

For example

Age (months) ± SD:

I: 8.48 ± 7.11

C: 7.92 ± 6.48

Sex (M:F):

I: 17:8

C: 19:6

Weight (kg) ± SD:

I: 6.67 ± 1.63
C: 6.69 ± 1.83

Groups comparable at baseline?

yes

clonidine from a 150

μg/ml ampoule was diluted and 1 μg/kg was drawn with a

tuberculin syringe and added to 0.5 ml of 0.5% bupivacaine;

the resulting mixture was reconstituted with saline to a

volume of 1 ml to maintain a bupivacaine concentration

of 0.25% (Group A; n = 25)

solution of 1 ml 0.25% bupivacaine solution was prepared

by adding 0.5 ml saline to 0.5 ml of 0.5% bupivacaine

(Group B; n = 25) by one of the authors, who was no

further involved in data collection and surgery

Length of follow-up:

12h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

There were no drop-outs in the study

because of the failed block.

1. Postoperative pain

Postoperative pain was assessed by a trained

postoperative nurse who was unaware of the drug given using Face, Legs, Activity, Cry, Consolability (FLACC) score

1.2. 6 hours

0-3 (no pain to mild pain) (%)

I: 24 (96)
C: 21 (84)

4-6 (moderate pain) (%)

I: 1 (4)
C: 3 (12)

7-10 (severe pain) (%)

I:: nil
C: nil

The qualitative pain relief was better with group A as at all times, and more patients in group A had lower scores.

3. Postoperative opioid consumption

Type of analgesia not reported.

Nineteen (76%) subjects did not require rescue

analgesia in group A up to 12 hours postoperatively, while

5(20%) subjects in group B did not require rescue drug

up to 12 hours.

4. Adverse events

4.4. Sedation

Sedation at extubation was assessed using University of Michigan sedation scale (UMSS)

Sedation score: 0:1:2:3

I: 6:12:6:1
C: 4:10:8:4

Study aim: To evaluate the efficacy of adding clonidine to bupivacaine in bilateral

infraorbital nerve block for hemodynamic changes, requirement of opioids, volatile agent,

and muscle relaxants intraoperatively and relief of pain postoperatively

Joshi, 2004

Type of study: RCT

Setting and country: single-centre, USA

Funding and conflicts of interest: not reported

Inclusion criteria: children

scheduled for elective surgery (unilateral hernia,

hydrocelectomy, or orchidopexy) by one of three

surgeons were enrolled in the study. Patients were eligible for participation if they were between

6 months and 6 years of age.

Exclusion criteria: known allergy or sensitivity to clonidine.

N total at baseline:

Intervention: 18

Control: 17

Important prognostic factors²:

For example

Age (months) ± SD:

I: 28 ± 22 (7–65)

C: 44 ± 31 (8–83)

Weight (kg)

I: 13 ± 4.7
C: 15 ± 6.1

Sex:

I: F 3 M 15

C: F 2 M 15

Groups comparable at baseline? The

groups did not differ significantly with respect to

sex, age, or weight (Table 1). PACU discharge time

also did not differ between the two groups (98 ± 40

in group C vs 104 ± 34 in group S).

The clonidine

group (group C) received 2 lgÆkg)1 of clonidine

(100 lgÆml)1) in addition to the bupivacaine.

The

saline group (group S) received an equal volume of

preservative-free normal saline.

Length of follow-up:

24h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

1.1.    PACU

faces scale by nurse

I: 6.7 ± 1.5
C: 6.8 ± 1.7

1.3. 24 hours - rest

The VAS was bounded with 0 representing no pain, and 10 representing worst imaginable pain, rated by parent.

I: 1.9 ± 2.7
C: 1.8 ± 1.9

24 hours – movement

I: 3.6 ± 3.3

C: 3.2 ± 2.2

3. Postoperative opioid consumption

Fentanyl was given if the child had observable

moderate or severe pain based on a faces scale.

3.1. PACU

There were significantly more patients in the group S who required fentanyl in the PACU (four patients in group C vs nine patients in group S; P < 0.05).

The amount of fentanyl did not differ between the two groups (0.6 ± 0.4 lgÆkg)1 in clonidine

vs 0.8 ± 0.5 lgÆkg)1 in the group S).

3.2. 24 hours

The number of doses of

acetaminophen/codeine

I: 2.6 ± 1.4
C: 2.8 ± 2.0

4. Adverse events

4.4. Sedation -POD 1

Sedation level

was scored with 0 corresponding to ‘asleep’ and 10 corresponding to ‘awake’

no numbers reported, author report “There was no difference between the groups with respect to sedation the night of surgery or the following morning.”

Study aim: to

determine whether caudal clonidine added to caudal bupivacaine

would decrease pain in paediatric patients undergoing surgery.

Koul, 2009

Type of study: RCT

Setting and country: single centre, India

Funding and conflicts of interest: not reported

Inclusion criteria:

40ASAI children

between 1-10 years of age weighing 5-20 kg,

who were scheduled to undergo inguinal herniotomy as daycare cases

Exclusion criteria:

Children with any contraindication to caudal block or having

congenital heart disease were excluded from the study

N total at baseline:

Intervention: 20

Control: 20

Important prognostic factors²:

For example

age (years) ± SD:

I: 3.45±2.06

C: 3.28± 1.65

Weight (kg)

I: 14.58±4.40

C: 13.45±6.04

Groups comparable at baseline?

Mean age, weight, surgical and recovery time were comparable between two groups

0.75 ml.kg-1 of

0.25% bupivacaine with 2μg.kg-1 of clonidine (Group C)

Caudal epidural injection of either 0.75ml.kg-

1 of 0.25% bupivacaine (Group B)

Length of follow-up:

24h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

OPS score (at 30

minutes, 1hour and 2hours)

1.1. PACU

1.2. 6 hours

1.3. 24 hours

(only mean reported)

Mean, SD

I: 4.55±0.25
C: 4.65± 0.25

4. Adverse events

4.2. Respiratory depression

decrease

of SpO2 less than 93% and required supplemental oxygen via mask

None of the children had SpO2value less than 95%.

4.4. Sedation

1: asleep,not arousable by verbal contact;

2: asleep, arousable by verbal contact; 3:

drowsy not sleeping;4: alert/aware (30minutes,

1hourand 4hours after the operation)

mean, SD

I: 2.83±0.47
C: 2.8± 0.45

Study aim: to examine the haemodynamic and respiratory effects of clonidine as an adjunct to bupivacaine caudal epidural analgesia and compare its analgesic efficacy with control group in which only bupivacaine was used, in paediatric day care procedures

Laha, 2012

Type of study: prospective, randomized, double‑blind

trial

Setting and country: single centre, India

Funding and conflicts of interest: Nil, none declared.

Inclusion criteria: ASA

grade I children, aged 2 to 11 years, weighing 5 to

30 kilograms, scheduled for lower abdominal, perineal, and

lower limb surgeries

Exclusion criteria: Patients

having cardiovascular, neurological diseases, coagulopathy,

infection or deformity of local site and where parents

refused to give consent were excluded from the study.

N total at baseline:

Intervention: 15

Control: 15

Important prognostic factors²:

For example

age (year) ± SD:

I: 4.8 (±2.6)

C: 4.7 (±2.6)

Weight (kg) ± SD:

I: 14.4 (±4.2)

C: 14.8 (±5.5)

Sex (M:F):

I: 11:4

C: 11:4

Groups comparable at baseline? Patients in the 2 groups were comparable regarding age,

weight, sex distribution, and duration of surgery

mixture of ropivacaine 0.2% (1 ml/kg) with clonidine 2 μg/kg (group B)

caudal injection of either plain ropivacaine 0.2% (1 ml/kg) (group A)

Length of follow-up:

24 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

Children’s Hospital Eastern Ontario Pain Scale (CHEOPS) at 0 hour , 4 hours, 8 hours, 12 hours,

16 hours, 20 hours and24 hours

1.1.    PACU

1.2. 6 hours

1.3. 24 hours

Results are presented in a graph, from which the exact scores cannot be read. At PACU, 4 hours, 8 hours and 24 hours, pain scores were (slightly) higher for C compared to I – with pain scores increasing over time.

4. Adverse events

4.1. Apnea

4.2. Respiratory depression

4.3. Hypotension

4.4. Sedation

4.5. Postoperative emergence delirium

The 2 groups

did not vary in respect to sedation or other adverse effect.

Study aim: to compare the post-operative pain relieving quality of %%i%%071ropivacaine 0.2% and clonidine mixture%% to that of plain ropivacaine 0.2% following caudal administration in children.

Mostafa, 2021

Type of study: prospective randomized controlled, double-blind

study

Setting and country: single-centre, Egypt

Funding and conflicts of interest: funding: not reported; CI: All authors reported no conflict of interest.

Inclusion criteria: children scheduled for laparoscopic orchiopexy aged between 3 and 8 years old and in American Society of

Anesthesiologists (ASA) physical status grade I–II

Exclusion criteria: Patients whose parents refused to consent for the study, had a history of developmental delay or mental retardation (making

observational pain intensity assessment difficult), with an

allergy to the study drugs, bleeding diathesis, renal, hepatic, cardiac, respiratory or neurological diseases, had signs of infection

at the site of the block or sleep apnea that may warrant

postoperative ventilation

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors²:

For example

age (year) ± SD:

I: 5.68 ± 1.7

C: 5.37 ± 1.6

Weight (kg):

I: 19.27 ± 3.7

C: 18.78 ± 4.1

Groups comparable at baseline? The initial demographic

parameters of these participants demonstrated no statistically

significant differences in terms of age, body weight,

stature (height), ASA status, duration of surgery and anesthesia time among the three groups of the study.

levobupivacaine plus clonidine (group C, n = 30)

levobupivacaine plus normal saline (group

B, n = 30)

Length of follow-up:

24hr

Loss-to-follow-up:

I: 0
C: 0

Incomplete outcome data:

I: 0
C: 0

1. Postoperative pain

Children's Hospital of Eastern Ontario Pain Scale (Mcheops)

1.1. PACU

I: 4.00 ± 0.1
C: 4.10 ± 0.3

1.2. 6 hours

Not reported

Alternative outcomes:

4 hours

I: 4.07 ± 0.3
C: 6.57 ± 2.0

8 hours

I: 7.33 ± 1.8
C: 5.03 ± 1.5

1.3. 24 hours

I: 4.13 ± 0.3
C: 4.13 ± 0.3

3. Postoperative opioid consumption

Patients scored >5 with modified CHEOPS received rescue analgesia with 15 mg/kg of intravenous paracetamol (Perfalgan, Paracetamol 1,000 mg; UPSA Laboratories).

3.1. PACU

3.2. 24 hours (within first postoperative day) – number of doses

One dose

I: 23 (76.7%)
C: 14 (46.7%)

Two doses

I: 7 (23.3%)
C: 16 (53.3%)

3.3. Total analgesic dose/24 hr (mg)

I: 361.17 ± 127.9
C: 429.00 ± 164.5

4. Adverse events

4.4. Sedation

sedation

score described by Culebras et al. (1. awake and alert, 2. sleeping but easily arouses to voice or light touch, 3. arouses

to loud voice or shaking, 4. arouses with painful stimuli and 5. cannot be aroused; Culebras et al., 2001).

I: 1.33 ± 0.1
C: 1.17 ± 0.1

Study aim: We

hypothesized that dexmedetomidine or clonidine could improve the analgesic profile

of levobupivacaine to the same extent during TAP block in children.

Narasimhamurthy, 2016

Type of study:

 prospective, double-blind, randomized, controlled study

Setting and country: single-centre, India

Funding and conflicts of interest: not reported

Inclusion criteria:

 ASA 1 children between 2-10 years of age, of either sex, scheduled to undergo infraumbilical surgeries (circumcision, herniotomy and orchidopexy)

Exclusion criteria:

Not reported

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors²:

For example

age (years) ± SD:

I: 4.8 + 1.7

C: 4.7 + 1.7

Weight (kg):

I: 13.73 + 2.8
C: 13.43 + 3.14

Sex (M/F):

I: 25/5

C: 26/4

Groups comparable at baseline? Yes; the groups were comparable with respect to age, weight, sex and duration of surgery difference was found to be insignificant

Group B: Received mixture of 0.2% Ropivacaine and preservative free Clonidine 1μg/kg.

Group A: Received mixture of 0.2% Ropivacaine and normal saline.

Length of follow-up:

24h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

FLACC; no of patients with pain score ≥ 4

1.1. PACU

Not reported

6 hours
I: 0
C: 18(60%)

1.3. 24 hours

I: 3(10%)
C: 2(6.6%)

3. Postoperative opioid consumption

Rescue medication was administered in the form of oral syrup of paracetamol 15mg/kg when the FLACC score was > 4.

3.1. PACU

3.2. 24 hours,

Number of rescue analgesic doses in 24 hours

One dose

I: 24
C: 4

Two doses

I: 6
C: 18

Three doses

I: 0
C: 8

4. Adverse events

4.2. Respiratory depression

I: 0
C: 0

4.4. Sedation in first two hours (n)

sedation score 0- awake, 1- arousable by voice, 2- arousable to pain, 3- unarousable.

Score = 0

I: 22
C: 22

Score = 1

I: 8
C: 8

Study aim:

 to show the optimum concentrations of Ropivacaine and Clonidine to maximize analgesia without side effects by evaluating its safety and efficacy.

Parameswari, 2010

Type of study: prospective,

randomised, controlled, double-blinded study

Setting and country: single-centre, India

Funding and conflicts of interest: Source of Support: Nil, Conflict of Interest: None declared

Inclusion criteria: ASA physical

status I – II, age one to three years, undergoing subumbilical

surgeries under general anesthesia (circumcision; orchidopexy; herniotomy)

Exclusion criteria: Children with sacral bone abnormalities, spina bifida,

coagulopathy and infection at the site of caudal injection

N total at baseline:

Intervention: 50

Control: 50

Important prognostic factors²:

age (months):

I: 19

C: 21

Sex (M/F):

I: 47/3

C: 47/3

Weight (kg):

I: 9
C: 10

Groups comparable at baseline? Analysis of patient results revealed no differences in

the demographic characteristics of the two groups

Bupivacaine with 1 μg/kg clonidine

Plain bupivacaine

Length of follow-up: 24 hours post-operatively

Loss-to-follow-up:

Not reported

Incomplete outcome

 Not reported

1. Postoperative pain

FLACC scale; 0 = No pain

1 - 3 = Mild pain

4 - 7 = Moderate pain

8 - 10 = Severe pain

1.2. 6 hours – pain score 0-3 (no pain or mild pain), n (%)

I: 33 (66)

C: 12 (24)

pain score 4-10 (moderate to severe pain), n (%)

I: 17 (34)

C: 38 (76)

3. Postoperative opioid consumption

Rescue medication was administered when the FLACC score was ≥ 4. Paracetamol suppository was used as rescue

medicine with a loading dose of 40 mg/kg followed by 20 mg/kg every six hours.

3.2. 24 hours

0 doses

I: 2
C: 9

One dose

I: 29
C: 34

Two does

I: 15
C: 7

Three doses

I: 4
C: 0

More patients in Group A (Plain bupivacaine) needed two or three doses of rescue medicines compared to patients in Group B (Clonidine with

bupivacaine)

4. Adverse events

4.2. Respiratory depression

oxygen saturation less than 93%, requiring oxygen by face mask

I: 0
C: 0

4.3. Hypotension

systolic blood pressure less than 70 mm Hg

I: 0
C: 0

Study aim: to evaluate the efficacy of clonidine added to bupivacaine in prolonging the

analgesia produced by caudal bupivacaine in children undergoing sub-umbilical surgery

Potti, 2017

Type of study: double-blind controlled study

Setting and country: single-centre, India

Funding and conflicts of interest: not reported

Inclusion criteria: ASA I-II; elective infraumbilical surgeries 

Exclusion criteria: any contradiction for caudal epidural and the study drugs; administration of any analgesic in the past 24h

N total at baseline:

Intervention: 25

Control: 25

Important prognostic factors²:

Age (years) ± SD:

I_B: 4.7 ± 2

I_C: 4.6 ± 1

C_A: 4.32 ± 2

Weight (kg):

I_B: 14.2 ± 4.4

I_C: 13.7 ± 3.8

C_A: 13.7 ± 4.2

Groups comparable at baseline?

Yes

Group B (n = 25) received levobupivacaine 0.25% 1 mL/kg with 1 mug/kg clonidine caudally and 5 mL of normal saline i.v

Group C (n = 25) received levobupivacaine 0.25% 1 mL/kg caudally and 1 mug/kg clonidine in 5 mL normal saline i.v

Group A (n = 25) received levobupivacaine 0.25% 1 mL/kg caudally and 5 mL of normal saline i.v

Length of follow-up:

24h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

CHIPPSS

1.1. PACU (1h)

I_B: 0=25

I_C: 0=25

C_A: 0=20; 1=3; 2=3; 3=0; ≥4=0

1.2.    6 hours

I_B: 0=6; 1=18; 2=1;

I_C: 0=1; 1=5; 2=12; 3=4; ≥4=3

C_A: 2=1; ≥4=24

1.3. 24 hours

I_B: 1=1; 2=3; 3=1; ≥4=20

I_C: 2=1; 4 ≥=24

C_A: 4 ≥=25

3. Postoperative opioid consumption

CHIPPS score ≥ 4, paracetamol 10 mg/kg i.v infusion over 10 min

3.1. PACU

3.2. 24 hours

3.3. Total

No of patients not required rescue analgesia

I_B: 5

I_C: 1

C_A: 0

4. Adverse events

4.2. Respiratory depression

I_B: 0

I_C: 0

C_A: 0

4.3. Hypotension

I_B: 0

I_C: 0

C_A: 0

4.4. Sedation

Ramsay sedation scale, mean ± SD:

1.1. PACU (1h)

I_B: 2.52 ± 0.51

I_C: 2.40 ± 0.50

C_A: 2.40 ± 0.50

1.3.    6 hours

I_B:  2.00 ± 0.00

I_C: 2.00 ± 0.00

C_A: 2.00 ± 0.00

1.3. 24 hours

I I_B: 2.00 ± 0.00

I_C: 2.00 ± 0.00

C_A: not reported

Study aim: to compare the effects of caudal an intravenous clonidine on postoperative analgesia produced by caudal levobupivacaine in children undergoing infraumbilical surgery

Priolkar, 2016

Type of study:

prospective, randomised, double-blind, controlled study

Setting and country: single-centre, India

Funding and conflicts of interest: none

Inclusion criteria:

 in 60 patients, over 18 months, from May 2010 to November 2011. They were between 1-10 years of age, of ASA Physical Status I, weighing 5-20 kg, scheduled to undergo infraumbilical operations in a tertiary hospital

Exclusion criteria:

 contraindication to caudal blockade, history of allergic reaction to Bupivacaine or Clonidine, ASA Physical Status > I and parental refusal.

N total at baseline:

Intervention: 30

Control:30

Important prognostic factors²:

For example

Age (years) ± SD:

I: 4.43+1.52

C: 4.63+1.73

Weight (kg) ± SD:

I:

13.10+3.48

C:

12.76+3.21

Groups comparable at baseline?

Yes

 Group: BC: Mixture of 1ml/kg of 0.125% Bupivacaine with preservative free Clonidine 1μ/kg.

 Group: B: 1ml/kg of 0.125% Bupivacaine solution.

Length of follow-up:

24 hours

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

3. Postoperative opioid consumption

Patients were given oral paracetamol syrup 15mg/kg body weight as rescue analgesic for a pain score of IV or V during the first 24 hours after surgery. Postoperative pain was assessed at the end of 2 hours and thereafter 2 hourly for 6 hours, then 4 hourly for 24 hours by the 5-point verbal pain score as follows [13].

I Asleep

II Awake but no pain.

III Mild pain (on touching area or movement)

IV Moderate pain (constantly cries or complains of pain)

V Severe pain (uncontrollable or excessive crying).

3.2. 24 hours

No. of patients receiving postoperative rescue analgesic during the first 24 hours after surgery, mean±SD

I: 1.9±0.48

C: 3.46±0.57

4. Adverse events

4.2. Respiratory depression

I: 0
C: 0

4.4. Sedation

Sedation score was assessed at 2 hours postoperative and then 2 hourly for 6 hours by the – 4-point patient sedation score (PPS) as follows [14]:

1) Asleep not arousable.

2) Asleep arousable by verbal contract.

3) Drowsy.

4) Alert Awake.

Number of patients

Score 4

I: 24
C:  26

Score 3

I: 5
C:  4

Score 2

I: 1
C: 0

Study aim: To evaluate the efficacy and side effects of caudal clonidine in a low dose of 1μg/kg combined with a low concentration of 0.125% solution of bupivacaine.

Rawat, 2019

Type of study: prospective, randomized, double-blind- controlled study

Setting and country: single-centre, India

Funding and conflicts of interest: not reported

Inclusion criteria: ASA I-II, +/- 20% ideal body weight and height. Planned for elective perineal surgeries

Exclusion criteria: parent’s refusal, contraindication for caudal block, and history of allergic reaction to levobupivacaine, clonidine, or tramadol

N total at baseline:

Intervention: 32

Control: 32

Important prognostic factors²:

Age (years) ± SD:

I: 4.14 ± 1.05

C:  4.16 ± 1.87

Sex (M/F):

I: 15/7

C: 14/8

Weight (kg) ± SD:

I: 11.64 ± 2.25

C: 12.37 ± 2.82

Groups comparable at baseline?

Yes

Group III – 0.25% levobupivacaine (1 mL.kg-1) with clonidine 1 mug.kg-1.

Group I - 0.25% levobupivacaine (1 mL.kg-1)

Length of follow-up:

12 h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

CHIPPS

1.1. PACU

1.2. 6 hours

1.3. 24 hours

Data presented in figure not readable. Trend is that pain scores are lower in group III compared to group I over all time points (0, 2, 4, 6, 8, 10, 12 H P.O.)

4. Adverse events

4.4. Sedation

Ramsay sedation score

Data presented in figure not readable. Trend is that sedation scores are higher in group III compared to group I over all time points (0, 2, 4, 6, 8, 10, 12 H P.O.)

Study aim: 

In this study, we compare the effects of tramadol and clonidine as an additive to levobupivacaine in caudal block in children undergoing perineal surgeries regarding hemodynamic changes, analgesic effects, and side effects.

Sanwatsarka, 2017

Type of study: prospective,

randomized, controlled, double-blinded study

Setting and country: single-center, India

Funding and conflicts of interest: Nil./ There are no conflicts of interest.

Inclusion criteria: American Society

of Anesthesiologists physical status I-II, age 1-7 years,

undergoing sub-umbilical surgeries under general anesthesia

Exclusion criteria: Children with local infection of the caudal area, history of

allergic reactions to local anesthetics, bleeding diathesis,

preexisting neurological or spinal diseases, mental retardation,

and neuromuscular disorders. Patients, in whom caudal anesthesia

failed or inadequate analgesia was present, were excluded

from study.

N total at baseline:

Intervention: 25

Control:25

Important prognostic factors²:

For example

Age (years) ± SD:

I: 6.28±1.21

C: 6.64±1.29

Weight (kg):

I: 15.48±3.34

C: 16.28±3.06

Sex (M/F):

I: 23:2

C: 22:3

Groups comparable at baseline? The study groups were comparable with respect to mean age,

weight, gender, duration, and type of surgery

Group BC received 1 ml/kg 0.25% bupivacaine + 1 μg/kg clonidine in normal saline

Group B received 1 ml/

kg 0.25% bupivacaine in normal saline

Length of follow-up:

24h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

FLACC pain score 1,2,3,4,8,12, 24 hrs

1.1. PACU

1.2. 6 hours

1.3. 24 hours

Data provided in a figure, not readable. The FLACC pain score never reached ≥4 during the first 3 h in any of the groups. However, the number of patients with FLACC pain score ≥4 were significantly more in Group B at the end of 4th (46%), 8th (56%) and 12th (72%) h compared to the other two groups. Furthermore at the end of 12th h, the number of patients with FLACC pain score ≥4 were significantly more in Group BM (40%) compared to Group BC (8%). More children in Group B had moderate to severe pain at 4 h, 8 h and 12 h postoperatively, compared to children in Group BC and Group BM.

3. Postoperative opioid consumption

In the PACU, the necessity for rescue medicine was decided by the pain score. Rescue medication was administered when

patients had score of ≥4 on at least 2 occasions or showed obvious signs of pain. Paracetamol suppository was used as

rescue medicine with a loading dose of 40 mg/kg followed by 20 mg/kg every 6 h.

3.1. PACU

3.2. 24 hours

3.3. Total

1 dose

I: 12%
C: 0%

2 doses

I: 84%
C: 40%

3 doses

I: 4%
C: 60%

4. Adverse events

4.2. Respiratory depression

A decrease in oxygen saturation <93%, requiring

oxygen by face mask

I: 1
C:0

4.3. Hypotension

Systolic blood pressure (SBP) <70 mm Hg

I: 0
C:0

4.4. Sedation

Four (4) point sedation score

1 Asleep, not arousable by verbal contact

2 Asleep, arousable by verbal contact

3 Drowsy not sleeping

4 Alert/awake

Measured 0,1,2,4,8,12h postoperatively

Mean score at 0h postoperatively

I: 1.88±0.2112
C: 2.84±0.2688

Mean score at 4h postoperatively

I: 3.08±0.2208
C: 3.8±0.32

Mean score at 12h postoperatively

I: 3.72±0.4032
C: 4±0.0

Study aim: to compare the intraoperative hemodynamics, postoperative analgesia, postoperative rescue analgesic requirement,

postoperative sedation and side-effects of clonidine and midazolam used as adjuvants to bupivacaine for caudal analgesia.

Shaikh, 2015

Type of study: prospective randomized double blind study

Setting and country: single-centre, India

Funding and conflicts of interest: funding not reported. Conflict of interest: none declared by the authors.

Inclusion criteria: age 1-12 years, ASA I/II; given IC; to undergo elective sub-umbilical, perineal and lower limb surgeries

Exclusion criteria: patients > 12 years, ASA > III, any contraindications to epidural anaesthesia

N total at baseline:

Intervention: 30

Control: 30

Important prognostic factors²:

For example

Age (months) ± SD:

I: 58.30 ± 27.92

C: 74.40 ± 37.34

Sex (M/F):

I: 27/3

C: 28/2

Weight (kg):

I: 14.67 ± 3.87

C: 14 ± 0.12

Groups comparable at baseline? yes

Group B received caudal 0.25% bupivacaine 1 ml/Kg with clonidine 1 μg/Kg as an adjuvant made to 0.5 ml with normal saline

Group A received caudal  0.25% bupivacaine plain with 0.5 ml Normal saline

Length of follow-up:

POD1

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

FLACC pain scale

1.1. PACU

1.2. 6 hours

1.3. 24 hours

Data presented in figure; values not readable. At 0 FLACC scale 0; at 4-8hr group B much lower score compared to group A; at 24 hours group B still lower, but less difference.

The score was 4 at 4 hrs in group A and at 12 hrs in group B.

3. Postoperative opioid consumption

FLACC ≥ 4; paracetamol 40 mg/kg

3.1. PACU

3.2. 24 hours

3.3. Total

One dose

I: 24
C: 2

Two doses

I: 6
C: 24

Three doses

I: 0
C: 4

4. Adverse events

4.2. Respiratory depression

I: 0
C: 0

4.3. Hypotension

I: 0
C: 1

4.4. Sedation

0-3 according to child’s alertness and arousability

Data presented in figure not readable. Sedation scores up to 8 hours postoperatively are lower in group A as compared to group B. at 8 hours, both groups score 0.

Study aim: to know the efficacy and safety of clonidine as an adjuvant to bupivacaine in single shot caudal block in children

Singh, 2012

Type of study: prospective randomized control trial

Setting and country: single-centre, Nepal

Funding and conflicts of interest: not reported

Inclusion criteria: Patients with ASA grade 1 and 2 coming for below umbilical surgeries that are under the age group age one to ten years weighing approximately between five to twenty kilograms

Exclusion criteria: Infection at the site of injection, bleeding disorders, patients who are on anticoagulant therapy, congenital anomalies of the spinal cord, congenital disorders, patients allergic to anesthetic drugs, surgeries extending more than 90 minutes, surgeries requiring anesthesia above T10 level, active CNS disorders and convulsive disorders.

N total at baseline:

Intervention: 20

Control: 20

Important prognostic factors²:

For example

Age (years) ± SD:

I: 5.45±2.5

C: 6.10±2.19

Weight (kg):

I: 14.70±3.8

C: 15.60±3.16

Groups comparable at baseline? All the four groups were comparable in relation to age and weight without any significant differences. Duration of anesthesia was also similar without any statistically significant differences.

Group BC received 0.75 ml/kg of 0.25% bupivacaine with 1 μg/ kg of clonidine in normal saline

Group B received 0.75 ml/kg of 0.25% bupivacaine in normal saline

Length of follow-up:

24 h

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Not reported

1. Postoperative pain

Pain score was evaluated using objective pain score scale by a trained nurse for 24 hours or till discharge (FLACC scale)

1.1. PACU

1.2. 6 hours

1.3. 24 hours

Data presented in figure not readable. Authors report “The pain score assessed using FLACC scale was compared between the four groups, and children in Group BC had lower pain scores, which was statistically significant(p<0.05)”.

3. Postoperative opioid consumption

If the score is more than 4 or if the patient complains of pain they were given oral paracetamol 10 mg/kg as rescue analgesia in the form of syrup/drops.

3.1. PACU

3.2. 24 hours

3.3. Total

“The requirement of rescue medicine was lesser in Group BC. Clonidine in a dose of 1 mcg/kg added to 0.25% bupivacaine for caudal analgesia, during sub-umbilical surgeries, prolongs the duration of analgesia of bupivacaine, without any side effects.”

4. Adverse events

4.2. Respiratory depression

Respiratory depression was considered if oxygen saturation less than 93% on breathing room air and if so supplemental oxygen via face mask was used at 4 liters per minute.

I: 0

C: 0

4.3. Hypotension

Intra-operative or post-operative decrease in systolic blood pressure and heart rate more than 30% of the baseline values were considered as severe hypotension and bradycardia respectively.

I: 0

C: 0

4.4. Sedation

Sedation was assessed by using sedation score. Assessment of sedation was done by sedation score at every hour for the first eight hours. Patient sedation score was defined as 1: Asleep, not arousable by verbal contact 2: Asleep, arousable by verbal contact, 3: Drowsy, not sleeping, 4: Alert/ awake.

Data presented in figure not readable and further not reported by the authors. From the figure it can be observed that the intervention group had higher sedation scores throughout all timepoints as compared to the control group.

Study aim:  To compare the efficacy of ketamine, fentanyl and clonidine in terms of quality and duration of analgesia they produce when added with caudal bupivacaine by single shot technique in children

Tripi, 2005

Type of study: RCT

Setting and country: single-centre, USA

Funding and conflicts of interest: not reported

Inclusion criteria: children 1 to

10 years old meeting American Society of Anesthesiologists

physical status classification I or II and undergoing ureteroneocystostomy.

Exclusion criteria:

not reported

N total at baseline:

Intervention: 18

Control: 17

Important prognostic factors²:

For example

age (months) ± SD:

I: 59.0 ± 30.4

C: 67.6 ± 30.5

Sex, no females (%):

I: 16 (89)

C: 12 (80)

Groups comparable at baseline? The 2 study groups were similar for mean age, weight and length of surgical procedure.

1 ml/kg

0.125% bupivacaine with 1 _g/kg clonidine

Caudal solutions also contained

1:400,000 epinephrine

preincision caudal block consisting of either 1 ml/kg 0.125% bupivacaine

Caudal solutions also contained

1:400,000 epinephrine

Length of follow-up:

24 hr

Loss-to-follow-up:

Not reported

Incomplete outcome data:

Two patients in the control group were excluded because of protocol violation.

1. Postoperative pain

Pain was measured using the Wong-Baker FACES Pain Rating Scale for children 1 to 3 years old, and the Faces, Legs, Activity, Cry and Consolability Scale for

children 4 years or older. With both scales a score of zero is considered no pain, and a score of 10 is considered worst possible pain.

1.1. PACU

I: 0.90
C: 1.18

1.2. 6 hours

1.3. 24 hours

Pain scores were measured at 15-minute intervals in the PACU and at 4-hour intervals on the postoperative ward until 24 hours postoperatively. à but data are not reported for last measures.

3. Postoperative opioid consumption

Intravenous morphine requirements for rescue therapy

3.1. PACU

I: 0.02 mg/kg

C: 0.05 mg/kg

3.2. 24 hours

I: 0.1 mg/kg

C: 0.2 mg/kg,

3.3. Total

Five of 18 patients in the clonidine-bupivacaine group received no postoperative morphine, compared to 1 of 15 in the bupivacaine group.

4. Adverse events

4.2. Respiratory depression

I: 0

C: 0

4.3. Hypotension

I: 0

C: 0

4.4. Sedation

Sedation was measured using a 5-point sedation score ranging from 1 (asleep, no response to painful stimulus) to 5 (crying, agitated or restless).

Mean initial sedation score was 3.2 for the treatment group and 3.0 for controls and mean of all PACU sedation scores was 3.4 for both groups.

Study aim: We evaluated whether clonidine, when added to bupivacaine, would significantly prolong caudal analgesia and decrease opioid requirements in children undergoing ureteroneocystostomy.

No absolute data were reported. Only in the text the mean values.

Visoiu, 2021

Type of study:

 randomized, double-blinded prospective study.

Setting and country:

 single center, USA

Funding and conflicts of interest: This work was supported by an educational seed grant from University of Pittsburgh Department of Anesthesiology and Perioperative Medicine. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Inclusion criteria: 10-17 years of age, weighed ≥34kg, and were scheduled for laparoscopic appendectomy during routine weekday hours

Exclusion criteria: Patients were excluded if they were <10 or ≥18 years of age, weighed < 34 or ≥100 kg, or had pre-existing cognitive impairment, developmental delay, chronic pain, and history of known allergies to medications used in the study or evidence of local infection at planned injection sites.

N total at baseline:

Intervention: 26, in final analysis 20

Control: 24, in final analysis 17

Important prognostic factors²:

Median age (Q1, Q3)

I: 13.0 (11.0, 15.0)

C: 13.0 (11.5, 15.5)

Sex, female %:

I: 46%

C: 54%

Median weight (kg) (Q1, Q3)

I: 53.9 (42.1, 63.0)

C: 56.3 (48.2, 66.2)

Groups comparable at baseline?

Yes

The R+C group received two 20 ml syringes with 10 ml of ropivacaine 0.5 % and 1 mcg/kg of clonidine (100 mcg =1 ml) for a total volume of 11 ml. Each patient in the R+C group received a total of 2 mcg/kg clonidine.

The RO group received two 20 ml syringes, each with 10 ml of ropivacaine 0.5% and a 1ml of normal saline (NS)

Length of follow-up:

Loss-to-follow-up:

Intervention: 0

Control: 0

Incomplete outcome data:

Intervention: 6

Missing periumilical numbness

Control: 7

Missing periumilical numbness

1. Postoperative pain

umbilical pain severity using the Numerical Pain Rating Scale (NPRS) (0 being no pain and 10 the worst imaginable pain). NPRS scores assessed every two hours from time of nerve block procedure.

1.1. PACU

I (n=25): 1.20 (2.55)
C (n=19): 1.79 (2.78)

1.2. 6 hours

I (n=18): 2.28 (2.49)
C (n=14): 2.43 (2.95)

2. Anxiety

STAIC anxiety scores

I (n=23): 29.0 (26.0, 32.0)
C (n=18): 30.0 (27.0, 30.0)

3. Postoperative opioid consumption

3.3. Total - Total Morphine Equivalents (mg/kg) perioperative

I (n=24): 0.20 (0.17, 0.24)
C (n=21): 0.22 (0.15, 0.36)

4. Adverse events

4.4. Sedation

PACU Sedation Level (0, 1, 2)

I (n=26): 18%, 77%, 5%
C (n=24): 19%, 76%, 5%

Study aim:

The primary aim of this study was to determine if the combination of ropivacaine plus clonidine in ultrasound (US)-guided rectus sheath nerve blocks was superior in prolonging periumbilical numbness compared to ropivacaine alone. Secondary aims included advancing the understanding of clonidine’s effect on perioperative analgesia, sedation, anxiolysis, and hemodynamics when used as an adjuvant in rectus sheath nerve blocks.