Article Analysis 1
The interpretation of research in health care is essential to decision making. By understanding research, health care providers can identify risk factors, trends, outcomes for treatment, health care costs and best practices. To be effective in evaluating and interpreting research, the reader must first understand how to interpret the findings. You will practice article analysis in Topics 2, 3, and 5.
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Search the GCU Library and find three different health care articles that use quantitative research. Do not use articles that appear in the Topic Materials or textbook. Complete an article analysis for each using the “Article Analysis 1” template.
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Doi: 10.5152/TJAR.2020.29863
Shilpa Goyal1 , Ankur Sharma2 , Devalina Goswami3 , Nikhil Kothari1 , Amit Goyal4 , Varuna Vyas5 ,
Richard Kirubakaran6 , Ranjit Sahu7 , Surjit Singh8
1Department of Anaesthesia and Critical Care, All India Institute of Medical Sciences (AIIMS), Rajasthan, Jodhpur, India
2Department of Trauma and Emergency (Anaesthesia) All India Institute of Medical Sciences (AIIMS), Rajasthan, Jodhpur, India
3Department of Anaesthesiology and Critical Care, All India Institute of Medical Sciences (AIIMS), New Delhi, India
4Department of Otorhinolaryngology, All India Institute of Medical Sciences (AIIMS), Rajasthan, Jodhpur, India
5Department of Pediatrics, All India Institute of Medical Sciences (AIIMS), Rajasthan, Jodhpur, India
6Department of Biostatistics, (South Asian Cochrane Centre), Christian Medical College Vellore, Tamil Nadu, India
7Department of Plastic Surgery, All India Institute of Medical Sciences (AIIMS), Rajasthan, Jodhpur, India
8Department of Pharmacology, All India Institute of Medical Sciences (AIIMS), Rajasthan, Jodhpur, India
Cite this article as: Goyal S, Sharma A, Goswami D, Kothari N, Goyal A, Vyas V, et al. Clonidine and Morphine as Adjuvants for Caudal Anaesthesia in Children: A Systematic Review
and Meta-Analysis of Randomised Controlled Trials. Turk J Anaesthesiol Reanim 2020; 48(4): 265-72.
Introduction
Caudal anaesthesia is the most commonly used mode of analgesia for patients in the paediatric age group who are
undergoing upper or lower abdominal surgeries. Caudal anaesthesia is safe and effective and can be used for both
intraoperative and postoperative analgesia in this age cohort (1). Local anaesthetic agents have a short duration of
action when used as single modalities; the addition of adjuvants to local anaesthetics prolongs the duration of post-
operative analgesia (2). There are many adjuvants which can be used to prolong the duration of caudal analgesia,
however, we have limited this analysis to a comparison between the effects of clonidine vs. morphine because, at this
moment in time, these are the only two drugs currently approved by US Food and Drug Administration for epidural
injection.
Corresponding Author: Ankur Sharma E-mail: [emailprotected]
Copyright 2020 by Turkish Society of Anaesthesiology and Reanimation – Available online at www.turkjanaesthesiolreanim.org
Received: 27.06.2019 Accepted: 05.09.2019
Available Online Date: 18.01.2020
Clonidine and Morphine as Adjuvants for
Caudal Anaesthesia in Children:
A Systematic Review and Meta-Analysis of
Randomised Controlled Trials
Abstract
Objective: The aim of this systematic review and meta-analysis is to compare the outcomes of morphine vs. clonidine use as adjuvants in caudal
anaesthesia. We are specifically focused on analgesic and side effect profiles.
Methods: We searched databases and trial registration sites and include here randomised controlled trials that compare the analgesic effects
of caudal clonidine vs. morphine as adjuvants on postoperative pain. The risk ratio for evaluating pain scores, the need for rescue analgesia
and all adverse effects were assessed. The i2 statistic was used to assess heterogeneity. We also assessed risk of bias with Cochranes Collab-
oration tool. The quality of evidence was assessed with Grading of Recommendations Assessment, Development and Evaluation (GRADE)
system.
Results: Four randomised controlled trials (including 166 patients) that evaluated the use of clonidine vs. morphine as adjuvants in caudal block
were included in this systematic review and meta-analysis. The pooled estimate for postoperative analgesia revealed no statistically significant
differences between the clonidine group compared to morphine group (MD=2.90; 95% CI 4.05 to 9.85; i2 93%). Significantly less postoperative
nausea and vomiting were reported among the patients that received clonidine vs. those that were treated with morphine (RR 0.57, 95% CI
0.36 to 0.90, i2 26%). There were no statistically significant differences between the two groups in assessments that included urinary retention,
pain scores or need for rescue analgesia at 24 hours.
Conclusion: Clonidine is just as effective as morphine when used an adjuvant to local anaesthetic for caudal block, and has a more desirable
side effect profile, particularly with respect to postoperative nausea and vomiting.
Keywords: Anaesthesia, analgesia, caudal, children, clonidine, morphine
265
Systematic Review
Paediatric Anaesthesia
https://orcid.org/0000-0002-8983-0953
https://orcid.org/0000-0001-9339-6988
https://orcid.org/0000-0002-5353-3383
https://orcid.org/0000-0002-9829-905X
https://orcid.org/0000-0002-4339-7541
https://orcid.org/0000-0002-1927-0487
https://orcid.org/0000-0002-5799-0303
https://orcid.org/0000-0003-2321-6798
https://orcid.org/0000-0002-8990-3235
Introduction of opioids, such as morphine, into the caudal
space can be advantageous; in contrast to the effects of local
anaesthetics, opioid drugs do not promote motor or sympa-
thetic blockade. Opioids promote adjuvant analgesia via local
action on spinal cord with limited systemic effects (3). Patients
receiving this treatment should be monitored for at least 24
hours in a post-anaesthesia care unit (PACU) and observed on
a frequent basis for level of consciousness and with sedation
scores (4).
The analgesic effect of epidural clonidine relates to direct
stimulation of 1 and 2 adrenoreceptors on the dorsal horn
grey matter of the spinal cord, thereby inhibiting the release
of nociceptive neurotransmitters (5). The most commonly en-
countered side effects of epidural clonidine are hypotension,
bradycardia and sedation. The hypotensive effect of clonidine
relates to its capacity to stimulate the 2 inhibitory neurons in
the vasomotor centre of medulla, which are actions that lead
to inhibition of norepinephrine release and central sympa-
thetic outflow. Clonidine also decreases the electrical activity
of preganglionic sympathetic nerves, stimulates central para-
sympathetic outflow and reduces sympathetic drive, thereby
resulting in bradycardia (6). Clonidine also activates 2 recep-
tors in locus coeruleus which suppresses the spontaneous dis-
charge from the nucleus and activates inhibitory neurotrans-
mitters including gamma aminobutyric acid. Clonidine also
depresses CNS function and results in sedation (6, 7).
Although there are many published randomised controlled
trials that have compared the efficacy of clonidine and
morphine as adjuvants in caudal blockade, we were unable
to identify any systematic reviews or meta-analyses on this
subject. As such, the aims of this review and systematic me-
ta-analysis are to compare the effects of adjuvant clonidine
vs. morphine for prolongation of postoperative analgesia
in paediatric surgical patients. Furthermore, we will review
the findings that address pain scores and the need for rescue
analgesia, as well as the incidence of side effects associated
with these drugs including postoperative nausea and vomiting
(PONV) and urinary retention.
Methods
We followed the recommendations of PRISMA (Preferred
Reporting Items for Systematic Reviews and Meta-Analyses)
(8) and Cochrane database (9) in preparing this systematic re-
view and a meta-analysis. Our study protocol and methods of
analysis were pre-specified and are registered in PROSPERO,
the international prospective register of systematic reviews,
Registration no.: CRD42018104720.
Search strategy
We searched Pubmed Central, Cochrane Register of Con-
trolled Trials, the Clinical Trial Registry and Google Scholar
from the time of inception to August 2018 for Randomised
Controlled Trials (RCTs) meeting our inclusion criteria and
without any language restrictions. The reference list of re-
ceived full articles were also searched. The following keywords
were searched in the aforementioned databases: (Caudal
OR Caudal analgesia OR Caudal Block) AND (Mor-
phine[Mesh] AND (Clonidine[Mesh] OR Randomised
Control Trial OR Trial) (Figure 1). The titles and abstracts
of articles retrieved from this search strategy were examined
by two independent authors and those deemed not relevant
were excluded. In the cases of abstracts and titles that did not
clarify eligibility, we attempted to retrieve full length articles.
Full texts of articles identified as potentially relevant were re-
viewed. Articles fulfilling the inclusion criterion were assessed
independently by two authors (SG and AS). Any discrepancy
was resolved by communication with a third author (DG).
Our search focused on RCTs which included direct compari-
sons between clonidine and morphine as adjuvants in caudal
anaesthesia for prolonging postoperative pain relief in paedi-
Main Points:
In this systematic review and meta-analysis, Morphine and Cloni-
dine were compared as adjuvants in caudal anaesthesia.
Four randomised controlled trials including 166 patients were
pooled for various outcomes.
We found that Clonidine is as effective as Morphine when used an
adjuvant to local anaesthetic for caudal block.
Clonidine has a more desirable side effect profile, particularly with
respect to postoperative nausea and vomiting.
There were no statistically significant differences between these 2
groups for urinary retention, pain scores or need for rescue analge-
sia at 24 hours. Figure 1. PRISMA flow diagram
13 of records after
duplicates removed
13 of records screened
4 of studies included
in qualitative synthesis
4 of studies included
in quantitative
synthesis
(meta-analysis)
9 of records excluded
(2 Non RCT: 7 Not
eligible)
21 of records
identified
through database
searching
No additional
records identified
through other
sources
Turk J Anaesthesiol Reanim 2020; 48(4): 265-72Goyal et al. Clonidine and Morphine in Caudal Analgesia
266
atric patients. We excluded non-paediatric patients (age>18
years) and studies that did not measure duration of analgesia
as a primary outcome. We also excluded data from review
articles, case reports, letter to editors, comments on published
articles and data from animal studies (Figure 1).
Primary and secondary outcomes
The primary outcome was duration of analgesia. This out-
come was measured as the time from administration of cau-
dal block to the time at which rescue analgesia was needed.
As expected, there was substantial heterogeneity in reporting
of outcomes and in assessing of pain in paediatric patients; as
in Vetter et al. (10), the time to administration of first rescue
analgesia was accepted as a useful outcome measure. The sec-
ondary outcomes were postoperative pain scores and adverse
effects including PONV and urinary retention.
Collection of data
The data were collected from the selected studies by three
independent authors (SG, AS and NK); all findings were
cross-checked. If the data included in a publication was not
sufficiently detailed for our needs, we attempted to contact
the authors by e-mail. The data extracted from the select-
ed studies included all the basic information as well as the
pre-specified outcomes of the RCTs. In order to simplify the
meta-analysis, we approximated medians and interquartile
ranges into means and corresponding standard deviations us-
ing methods as described in Cochrane library (9).
Assessment of risk of bias in independent studies
Two authors (SG and AS) independently assessed the risk of
bias in the individual selected studies. In the case of any dis-
crepancy, a common consensus was reached with the third
author (DG).Trials with one or more domains of unclear or
high risk of bias were designated as such.
Assessment of quality of evidence
We used Grading of Recommendations Assessment, Devel-
opment and Evaluation (GRADEpro) methodology for as-
sessing the overall quality of evidence for each outcome (11).
The quality of evidence for each primary or secondary out-
come was graded as high, moderate, low or very low.
Results
A summary of the four clinical trials included in this me-
ta-analysis are listed in Table 1. The selected clinical trials
include a total of 166 patients. GRADE summary of findings
Table 1. Characteristics of studies included in this meta-analysis
Definition
Number Amount of the
of patients LA used of Scoring duration Dose of Dose of
Authors/ (clonidine/ for caudal LA used tool of Clonidine Morphine
S.No Year Age morphine) Surgery block (ml kg1) for pain analgesia (mcs kg-1) (mcs kg-1)
1 Luz (12) 6 months 18/18 Orchidopexy, 0.18% 1.5 OPS Time from 1 30
1999 to 6 years Hernia repair, bupivacaine caudal block
Circumcision to first need
of systemic
analgesia
2 Vetter (10) 6 months 20/20 Ureteric re- 0.2% 1 FLACC Time from 2 50
2007 to 6 years implantation ropivacaine PACU
admission to
first
postoperative
FLACC
pain score of
4 or more
3 Singh (3) 16 25/25 Upper 0.2% 1.25 FLACC Time from 2 30
2011 years abdominal bupivacaine caudal block
surgery to first need
for systemic
analgesia
4 Fernandez 110 20/20 Infraumbili- 0.166% 1 FLACC Time from 1 20
(5) 2011 years calurological bupivacaine caudal block
and genital with to first need
procedures epinephrine for systemic
(1:600000) analgesia
LA: local anaesthetic drug; OPS: objective pain scale; FLACC: face, legs, activity, cry, consolability scale; PACU: post-anaesthesia care unit
Turk J Anaesthesiol Reanim 2020; 48(4): 265-72 Goyal et al. Clonidine and Morphine in Caudal Analgesia
267
in which the use of clonidine versus morphine is compared
are included in Table 2.
Duration of analgesia
Two of the selected studies (3, 12) reported on the duration of
analgesia; the other two studies (5, 10) included data that were
not suitable for meta-analysis. Taken together, the two suitable
studies included a total of 66 participants, 32 in the group that
received clonidine with local anaesthetic and 34 in the group
that were treated with morphine with local anaesthetic. The
pooled estimate demonstrated no statistically significant dif-
ferences between the two groups (MD=2.90, 95% CI 4.05 to
9.85, i2 93%, very low certainty evidence; Figure 2). The true
observed heterogeneity between these studies was 94%; this
finding indicates that results are significantly different among
the studies. Variability between the studies was incorporated in
the analysis by using a random effect rather than a fixed effect
model. The data available were not sufficient for subgroup anal-
ysis. These results overall were graded as low certainty evidence.
Postoperative nausea and vomiting: All four studies
(3, 5, 10, 12) provided data addressing PONV. In the cloni-
dine group, 17/83 patients (20.5%) and the morphine group
30/83 patients (36.1%) reported this outcome. There were
significantly fewer reports of PONV among the patients
receiving clonidine group than among those receiving mor-
phine (RR-0.57, 95% CI 0.36 to 0.90, i2, 26%, low cer-
tainty evidence; Figure 3a).
Urinary retention: The incidence of urinary retention was
reported in only two (5, 12) of RCTs (total 76 patients). There
were no statistically significant differences between the two
Table 2. Summary of findings
Clonidine compared to morphine in caudal analgesia in children: a systematic review and meta-analysis of
randomised controlled trials
Patient or population: caudal analgesia in children: a systematic review and meta-analysis of randomised controlled trials
Intervention: Clonidine
Comparison: Morphine
Anticipated absolute of Certainty of
effects* (95% CI) Relative effect participants the evidence
Outcomes Risk with Morphine Risk with Clonidine (95% CI) (studies) (GRADE) Comments
Duration of The mean duration The mean duration of – 66
analgesia of analgesia was 0 analgesia in the intervention (2 RCTs) VERY LOW
group was 2.9 higher (4.05
lower to 9.85 higher)
PONV 361 per 1,000 220 per 1,000 RR 0.57 166
(112 to 427) (0.36 to 0.90) (4 RCTs) LOW
Urinary 53 per 1,000 11 per 1,000 RR 0.20 76
Retention (1 to 206) (0.01 to 3.92) (2 RCTs) LOW
Rescue 379 per 1,000 607 per 1,000 RR 1.60 116
Analgesia (288 to 1,000) (0.76 to 3.36) (3 RCTs) VERY LOW
Pain Scores – – – 116
(3 RCTs) LOW
*The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the
intervention (and its 95% CI).
CI: Confidence interval; MD: Mean difference; RR: Risk ratio; SMD: Standardised mean difference, RCT: randomised controlled trial, PONV:
Postoperative nausea vomiting
GRADE Working Group grades of evidence
High certainty: We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate certainty: We are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a
possibility that it is substantially different.
Low certainty: Our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect.
Very low certainty: We have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect.
Figure 2. Forest plot for the primary outcome of
duration of analgesia
Turk J Anaesthesiol Reanim 2020; 48(4): 265-72Goyal et al. Clonidine and Morphine in Caudal Analgesia
268
treatment groups (RR0.20, 95% CI 0.01 to 3.92, heteroge-
neity, not applicable, low certainty evidence; Figure 3b).
Need for rescue analgesia: Three studies (5, 10, 12) with
a total 116 participants contributed findings that addressed
the need for rescue analgesia. We found no statistically signif-
icant differences regarding the need for rescue analgesia at 24
hours after surgery in the group that received clonidine com-
pared to group that received morphine (RR 1.60, 95% CI
0.76 to 3.36, i2, 67%, very low certainty evidence) (Figure 4a).
Pain scores: Pain was measured using various scoring tools;
as such, we analysed the data using standardised mean differ-
ence (SMD) methods. Results from three studies (5, 10, 12)
with 116 participants were consistent with one another; no
statistically significant differences were observed between the
treatment groups (SMD 0.22, 95% CI 0.14 to 0.59, i2 0%,
low certainty evidence (Figure 4b). Of note, there were no
pain scores included in the trial reported by Singh et al. (3).
Objective Pain Scale (OPS) was used for pain assessment in
Luz et al. (12) In the other two studies (5, 10) the paediatric
Faces Legs Activity Cry Consolability (FLACC) pain scale
was used to assess the need for rescue analgesia.
Risk of Bias: A tool from the Cochrane Collaboration was
used to assess the risk of bias in each study. Risk of bias relat-
ed to randomisation, allocation concealment, attrition and se-
lective reporting, performance and detection bias was found
to be low for most of the trials (Figure 5).
Publication bias: Publication bias is low. The current re-
view includes only randomised trials and does not take into
account any pilot or cohort studies; this was as per the inclu-
sion criteria listed in the Methods.
Discussion
The mechanisms by which clonidine and morphine promote
caudal anaesthesia are unique and distinct. Several mecha-
nisms have been postulated for analgesic action of clonidine
in this setting. Clonidine crosses the blood-brain barrier and
combines with 2 adrenoceptors at spinal and supraspinal
sites, thereby producing analgesia. Clonidine also elicits di-
rect suppression of the spinal cord nociceptive neurons and
suppresses peripheral sensory A and C nerve fibre neuro-
transmission. Likewise, the pharmacokinetics of clonidine
suggests that it may also function by inducing vasoconstric-
tion through 2b adrenoceptors which are located at the pe-
ripheral vascular smooth muscles (13).
Caudal clonidine in combination with bupivacaine has been
used at different doses; increasing the dose of clonidine from
1 g kg1 to 2 g kg1 had no impact on its efficacy. Lee et al.
(14) compared 0.25% bupivacaine at 1 mL kg1 combined
with either normal saline or clonidine at 2 g kg1; mean du-
ration of caudal analgesia was 5.21.2 hours and 9.82.1
hours, respectively (p<0.0001). Similarly, Singh et al. (15)
reported that the mean duration of caudal analgesia with
Figure 4. a, b. Analysis of the pooled data for (a) numbers
of patients requiring postoperative rescue analgesia (b)
postoperative pain scores
Figure 5. Risk of bias of the included trials
Figure 3. a, b. Analysis of the pooled data for (a)
postoperative nausea and vomiting and (b) urinary
retention
Turk J Anaesthesiol Reanim 2020; 48(4): 265-72 Goyal et al. Clonidine and Morphine in Caudal Analgesia
269
0.75 mL kg1 of 0.25% bupivacaine combined with 1 g kg1
of clonidine was significantly longer (629.06286.32 min)
than observed in response to any of the other study groups.
The analgesic effect of morphine can be attributed to its local
action on opioid receptors at the spinal cord (16). Morphine
is rapidly transferred from the epidural space to peripheral
circulation and reaches a maximum concentration in plasma
within 10 min after caudal block. Once in plasma, its half-
life is approximately 2 hours, and the major pathway for its
elimination is conjugation with glucuronic acid, forming
morphine-6-glucuronide and morphine-3-glucuronide. The
former metabolite is a potent analgesic compound in animal
models (17). In humans, morphine-6-glucuronide produces
similar pain relief, dysphoria and sedation with less respiratory
depression than the parent morphine; morphine-3-glucuron-
ide lacks significant activity (18). In children, adding morphine
at 0.05 mg kg1 to 0.125% bupivacaine improves the quality
and prolongs postoperative analgesia after orchidopexy (3).
However, in a retrospective study, 138 children received 0.07
mg kg1 of morphine in a caudal block, with 11 patients (near-
ly 8%) reporting clinically significant hypoventilation (4).
Fernandes et al. (5) emphasised that the use of opioids in cau-
dal epidurals in children has been questioned due to side ef-
fects, patient discomfort, delayed patient discharge and mar-
ginal efficacy. Use of morphine in caudal anaesthesia does
not seem to be justified for minor procedures including those
that are performed as day-case surgery; pain control for these
procedures can typically be achieved with non-opioid agents.
Use of morphine as a caudal adjuvant might be reserved for
those procedures that require intensive postoperative analge-
sia with intravenous opioids.
Our meta-analysis included two randomised trials that fo-
cused on postoperative analgesia; the findings presented in
the other two studies were not fully suitable for meta-analysis.
Overall, the results revealed no statistically significant differ-
ences between the clonidine group vs. the morphine group
for postoperative analgesia (MD=2.90, 95% CI 4.05 to 9.85,
i2 93%, very low certainty evidence).The heterogeneity was
93%; the difference in the magnitude of the effects observed
may be the result of different volumes and doses of local an-
aesthetic and drugs used. We inferred from this analysis that
morphine as an adjuvant provided an equivalent duration of
analgesia when compared to clonidine.
There was also no significant difference in need for rescue
analgesia, as assessed by pain scores in three randomised trials
(5, 10, 12). The report of Singh et al. (3) made no mention of
pain scores or the need for rescue analgesia; the authors did
not reply to our e-mail queries, and as such, we excluded this
study from the assessment of these two criteria (Table 2). Luz
et al. (12) used OPS as the pain score; rescue analgesia was
administered when the value was greater than 4. The remain-
ing trials (5, 10, 11) used FLACC for pain assessment; patients
were given rescue analgesia when score was 4.
PONV was reported more frequently and with higher inci-
dence in the group receiving morphine than in the clonidine
group (p=0.02). Neuraxial opioids have been previously asso-
ciated with a higher risk of PONV (19, 20); the 5-HT3 antag-
onist, ondansetron, is effective at reducing PONV secondary
to epidural morphine (21). In the study presented by Fernan-
dez et al. (5), the incidence of PONV was higher in morphine
group (20 mcg kg1) and likewise in a comparable study by
Wolf et al. (22), in which morphine was used at a dose of
50 mcg kg1. No prophylactic antiemetic therapy was used
in these studies, which permits a better assessment of the risk
of PONV. Vetter et al. (10) reported that a significantly larger
number of children experienced PONV in response to mor-
phine than in response to clonidine (80% vs. 50%; p=0.01),
and noted the larger need for antiemetics in in the former
group.
Urinary retention was comparable in the two groups. Fer-
nandez et al. (5) reported urinary retention in two patients in
morphine group and none in clonidine group. Urinary reten-
tion was relieved by simple measures.
Fernandez et al. (5) also reported that two patients in the mor-
phine group developed pruritis but not treatment was neces-
sary. Singh et al. (3) reported pruritis in 16% of the children
in the morphine group vs. none in clonidine group, a finding
that was statistically significant (p=0.03).
Vetter et al. (10) reported a higher incidence of pruritis in
the morphine group as compared to clonidine group and was
statistically significant (p=0.007).
Fernandez et al. (5) also reported no significant changes in
hemodynamic parameters. This result was consistent with
those reported in other studies (15, 23, 24). Luz et al. (12) also
observed a slight decrease in mean arterial pressure, together
with changes in heart and respiratory rates that were similar
in both the groups. Singh et al. (3) observed no incidence of
bradycardia or hypotension in either group.
Caudal morphine has been associated with respiratory de-
pression, a finding that has been reported primarily in chil-
dren less than 3 months of age and that has been associated
with doses of caudal morphine varying from 40 to 70 g kg1.
The study of Fernandez et al. (5) included no mention of re-
spiratory depression, although the study was not sufficiently
powered to detect this as a side effect. Similarly, Luz et al.
(12) reported no evidence of respiratory depression after 30
Turk J Anaesthesiol Reanim 2020; 48(4): 265-72Goyal et al. Clonidine and Morphine in Caudal Analgesia
270
g kg1 of morphine. Although this side effect is known to be
dose dependent (4, 25), epidural morphine at doses as low as
40 g kg1 has resulted in respiratory depression (26, 27). Attia
et al. (28) recommended continuous, mandatory respiratory
monitoring for at least 22 hours in children who were treated
with 50 g kg1 morphine as this has been associated with
a decreased ventilatory response to CO2. A literature search
suggested that epidural clonidine, given in low dose (15 g
kg1) had no impact on respiratory function in children (23-
25). Singh et al. (3) reported no incidence of respiratory de-
pression in either group.
The report of Fernandez et al. (5) did not include sedation as
a side effect. The time to emergence from anaesthesia was not
prolonged in either the morphine or clonidine groups, results
that suggest that the doses used in this study had no signifi-
cant impact on sedation. Luz et al. (12) compared the analgesic
efficacy, anaesthetic requirements and operation time and all
outcomes were comparable in the two groups, although they
noted that the longer recovery time observed among those in
the clonidine group might be related to increased sedation (24,
29). Singh et al. (3) observed that the duration of sedation was
significantly higher among those in the clonidine group as com-
pared to the morphine group (p<0.01). Other studies suggest
that there are no differences in the incidence of sedation in
comparisons among agents used for caudal analgesia (15, 25).
Conclusion
Clonidine is equivalent to morphine as an analgesic when
each is used as an adjuvant to local anaesthetic for caudal
block. Clonidine has a more desirable side effect profile, par-
ticularly in terms of PONV.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept S.G., A.S.; Design S.G., A.S.;
Supervision N.K., V.V.; Resources D.G.; Materials A.G., R.S.;
Data Collection and/or Processing S.G., A.S.; Analysis and/or
Interpretation R.K., S.S.; Literature Search A.S., V.V.; Writing
Manuscript S.G., A.S., V.V.; Critical Review A.G., V.V., R.S.;
Other N.K., D.G., A.G., R.S.
Conflict of Interest: The authors have no conflicts of interest to
declare.
Financial Disclosure: The authors declared that this study has
received no financial support.
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