YAJEM-158866; No of Pages 5

American Journal of Emergency Medicine xxx (xxxx) xxx

Contents lists available at ScienceDirect

American Journal of Emergency Medicine

journal homepage: www.elsevier.com/locate/ajem

Comparing the analgesic effect of intravenous paracetamol with

morphine on patients with renal colic pain: A meta-analysis of
randomized controlled studies
Xu Zhili, Chen Linglong, Jin Shuang, Yang Baohua ⁎
Department of Emergency, Wenzhou People Hospital, Wenzhou, P.R. China, Zhejiang, 325000, China

a r t i c l e i n f o a b s t r a c t

Article history: Introduction: The choice of intravenous paracetamol or morphine for the pain control of renal colic remains con-
Received 22 October 2019 troversial. We conduct a systematic review and meta-analysis to compare the analgesic efficacy and safety of in-
Received in revised form 28 March 2020 travenous paracetamol with morphine for renal colic pain.
Accepted 30 March 2020 Methods: We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through Septem-
Available online xxxx
ber 2019 for randomized controlled trials (RCTs) assessing the analgesic efficacy and safety of intravenous para-
cetamol versus morphine for renal colic pain. This meta-analysis is performed using the random-effect model.
Keywords:
Paracetamol
Results: Five RCTs are included in the meta-analysis. Intravenous paracetamol can lead to significantly lower pain
Morphine scores at 30 min (standard mean difference (Std. MD) = −0.40; 95% confidence interval (CI) = −0.68 to −0.12;
Pain control P = 0.005) and incidence of dizziness (risk ratio (RR) = 0.06; 95% CI = 0.01 to 0.48; P = 0.007) than morphine
Renal colic for renal colic pain. There is no statistical difference of pain scores at 15 min (Std. MD = −0.80; 95% CI = −1.84
Randomized controlled trials to 0.24; P = 0.13), analgesic rescue (RR = 0.73; 95% CI = 0.45 to 1.19; P = 0.21), the incidence of adverse events
(RR = 0.60; 95% CI = 0.35 to 1.03; P = 0.06), nausea or vomiting (RR = 0.61; 95% CI = 0.20 to 1.87; P = 0.38)
between two groups.
Conclusions: Intravenous paracetamol may result in lower pain scores at 30 min than morphine for renal colic
pain, and more studies should be conducted to compare their analgesic efficacy.
© 2020 Published by Elsevier Inc.

1. Introduction [16-18]. In addition, NSAIDs and opioids are unavailable in some

Patients with renal colic pain are very common in the emergent
department and have obviously reduced quality of life [1-5]. Oral
drugs are always not effective to control the renal colic pain, and
thus it is urgent to apply some intravenous analgesics [6,7]. Opioids
such as morphine are widely used for the relief of renal colic pain
because of its good analgesic effect, but may result in serious adverse
events such as hypotension, respiratory depression, apnea and even
intolerance [8-12]. The addiction is also documented while taking
opioids [13-15].
Nonsteroidal anti-inflammatory drugs (NSAIDs) have effective
analgesic effect in acute renal colic, but may be associated with
potential adverse effects such as platelet dysfunction, nephropathy,
and increasing cardiovascular mortality in ischemic heart disease
⁎ Corresponding author at: NO.57 Canghou Street, Wenzhou, Zhejiang Province, P.R.
China 325000.
E-mail address: cjn16816899@163.com (Y. Baohua).
emergency departments, and the alternative drugs with adequate
analgesic property and few side effects are crucial for the patients
with acute renal colic. Intravenous paracetamol is broadly used as
an effective pain reliever in emergency department with few side
effects [19-21]. Several studies demonstrated that intravenous
paracetamol might be effective and safe for the relief of renal colic
[22,23]. In one RCT involving 54 patients in each group, intravenous
acetaminophen was associated with substantially reduced pain
scores at 30 min after drug administration than that in the mor-
phine group (P = 0.0001) [24]. In contrast, another study compar-
ing intravenous morphine with acetaminophen for renal colic pain
revealed that morphine led to greater pain relief than acetamino-
phen [6].
Several studies have compared intravenous paracetamol with
morphine for the pain control of renal colic, but there are some
conflicting results [6,24-26]. This systematic review and meta-
analysis of RCTs aims to compare the analgesic efficacy and safety
of intravenous paracetamol versus morphine for the relief of
renal colic pain.

https://doi.org/10.1016/j.ajem.2020.03.061
0735-6757/© 2020 Published by Elsevier Inc.

Please cite this article as: X. Zhili, C. Linglong, J. Shuang, et al., Comparing the analgesic effect of intravenous paracetamol with morphine on
patients with renal colic..., American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.03.061
2 X. Zhili et al. / American Journal of Emergency Medicine xxx (xxxx) xxx

Fig. 1. Flow diagram of study searching and selection process.

2. Materials and methods and Meta-analysis statement and Cochrane Handbook for Systematic
Reviews of Interventions [27,28]. Because only previously published
This systematic review and meta-analysis are performed based on data are used for this analysis, ethical approval and patient consent
the guidance of the Preferred Reporting Items for Systematic Reviews are not required.

Table 1
Characteristics of included studies

NO. Author Paracetamol group Morphine group Jada

scores
Number Age Female Hematuria Baseline Methods Number Age Female Hematuria Baseline Methods
(n) (n) pain (n) (n) pain
intensity intensity

1 Yazdani 50 33.51 17 26 76.1 A single dose of 50 33.51 11 32 79.9 A single dose of 4

2018 ± 10.12 ± 13.9 1 g intravenous ± 10.12 ± 15.3 10 mg
paracetamol in intravenous
100 mL normal morphine sulfate
saline during in 100 mL normal
15 min saline during
15 min
2 Masoumi 54 36.07 11 – 8.84 One gram of 54 34.96 15 – 9.14 0.1 mg/kg 4
2014 ± 9.7 ± 1.37 intravenous ± 8.94 ± 1.13 morphine in
acetaminophen 100 mL normal
in 100 mL saline
normal saline
3 Azizkhani 62 38.40 20 – – 1 g intravenous 62 39.73 20 – – 10 mg 3
2013 ± 11.60 acetaminophen ± 11.62 intravenous
morphine
4 Serinken 38 29.1 10 33 – Intravenous 35 31.3 12 32 – Intravenous 5
2012 ± 8.2 paracetamol ± 9.0 0.1 mg/kg
(1 g) morphine
5 Bektas 46 35 15 33 73 Intravenous 49 39 22 36 78 Intravenous doses 4
2009 ± 10 (55–87), doses of ± 11 (64–98) of 0.1 mg/kg
median paracetamol morphine
(IQR) (1 g)

IQR, interquartile range.

Please cite this article as: X. Zhili, C. Linglong, J. Shuang, et al., Comparing the analgesic effect of intravenous paracetamol with morphine on
patients with renal colic..., American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.03.061
 X. Zhili et al. / American Journal of Emergency Medicine xxx (xxxx) xxx 3

Fig. 2. Forest plot for the meta-analysis of pain scores at 15 min.

2.1. Literature search and selection criteria
We have systematically searched several databases including
PubMed, EMbase, Web of science, EBSCO, and the Cochrane library
from inception to September 2019 with the following keywords: “para-
cetamol” or “acetaminophen”, and “morphine”, and “renal colic”. The
reference lists of retrieved studies and relevant reviews are also hand-
searched and the process above is performed repeatedly in order to in-
clude additional eligible studies.
The inclusion criteria are presented as follows: (1) study design is
RCT, (2) patients are diagnosed with renal colic pain, and (3) interven-
tion treatments are intravenous paracetamol versus morphine.
2.2. Data extraction and outcome measures
Some baseline information is extracted from the original studies,
and they include first author, number of patients, age, female, weight,
hematuria, baseline pain intensity and detail methods in two groups.
Data are extracted independently by two investigators, and discrepan-
cies are resolved by consensus. We have contacted the corresponding
author to obtain the data when necessary.
The primary outcomes are pain scores at 15 min and 30 min. Second-
ary outcomes include analgesic rescue, adverse events, nausea,
vomiting, and dizziness.
2.3. Quality assessment in individual studies
The methodological quality of each RCT is assessed by the Jadad
Scale which consists of three evaluation elements: randomization
(0–2 points), blinding (0–2 points), dropouts and withdrawals (0–1
points) [29]. One point would be allocated to each element if they
have been conducted and mentioned appropriately in the original arti-
cle. The score of Jadad Scale varies from 0 to 5 points. An article with
Jadad score ≤ 2 is considered to have low quality. The study is thought
to have high quality if Jadad score ≥ 3 [30,31].
2.4. Statistical analysis
We assess standard mean difference (Std. MD) with 95% confidence
interval (CI) for continuous outcomes (pain scores at 15 min and
30 min) and risk ratio (RR) with 95% CIs for dichotomous outcomes
(analgesic rescue, adverse events, nausea and vomiting, dizziness).
Heterogeneity is evaluated using the I2 statistic, and I2 N 50% indicates
significant heterogeneity [31,32]. The random-effects model is used
for all meta-analysis. We search for potential sources of heterogene-
ity when encountering significant heterogeneity. Sensitivity analysis
is performed to detect the influence of a single study on the overall
estimate via omitting one study in turn or performing the subgroup
analysis. Owing to the limited number (b10) of included studies,
publication bias is not assessed. Results are considered as statisti-
cally significant for P b 0.05. All statistical analyses are performed
using Review Manager Version 5.3 (The Cochrane Collaboration,
Software Update, Oxford, UK).
3. Results
3.1. Literature search, study characteristics and quality assessment
Fig. 1 shows the detail flowchart of the search and selection results.
264 potentially relevant articles are identified initially and five RCTs are
finally included in the meta-analysis [6,22,24-26].
The baseline characteristics of five included RCTs are shown in
Table 1. These studies are published between 2009 and 2018, and the
total sample size is 500. Among the included RCTs, 1 g intravenous para-
cetamol is compared to 10 mg intravenous morphine [6,25] or
0.1 mg/kg morphine [22,24,26].
Among the five included RCTs, three studies report pain scores at
15 min [22,24,26], four studies report 30 min [22,24-26], two studies re-
port analgesic rescue [22,24], three studies report adverse events
[22,24,26], four studies report nausea and vomiting [6,22,24,26], and
two studies report dizziness [24,26]. Jadad scores of the five included
studies vary from 3 to 5, and all five studies have high-quality.
3.2. Primary outcomes: pain scores at 15 min and 30 min
The random-effect model is used for the analysis of primary out-
comes. The results find that compared to morphine group for renal
colic pain, paracetamol shows no obvious impact on pain scores at
15 min (Std. MD = −0.80; 95% CI = −1.84 to 0.24; P = 0.13). There
is significant heterogeneity among the studies (I2 = 94%, heterogeneity
P b 0.00001, Fig. 2). However, paracetamol can result in significantly
lower pain scores at 30 min than morphine (Std. MD = −0.40; 95%
CI = −0.68 to −0.12; P = 0.005) with low heterogeneity among the
studies (I2 = 46%, heterogeneity P = 0.14, Fig. 3).

Fig. 3. Forest plot for the meta-analysis of pain scores at 30 min.

Please cite this article as: X. Zhili, C. Linglong, J. Shuang, et al., Comparing the analgesic effect of intravenous paracetamol with morphine on
patients with renal colic..., American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.03.061
4 X. Zhili et al. / American Journal of Emergency Medicine xxx (xxxx) xxx

Fig. 4. Forest plot for the meta-analysis of analgesic rescue.

Fig. 5. Forest plot for the meta-analysis of analgesic rescue.

3.3. Sensitivity analysis
There is significant heterogeneity for pain scores at 15 min, while
low heterogeneity remains for pain scores at 30 min. Thus, we perform
the sensitivity analysis to detect the heterogeneity for pain scores at
15 min by omitting one study in turn, but there is still significant
heterogeneity.
3.4. Secondary outcomes
In patients with renal colic pain, intravenous paracetamol and mor-
phine show similar analgesic rescue (RR = 0.73; 95% CI = 0.45 to 1.19;
P = 0.21; Fig. 4), the incidence of adverse events (RR = 0.60; 95% CI =
0.35 to 1.03; P = 0.06; Fig. 5), nausea and vomiting (RR = 0.61; 95%
CI = 0.20 to 1.87; P = 0.38; Fig. 6). In addition, intravenous paracetamol
is associated with significantly reduced incidence of dizziness (RR =
0.06; 95% CI = 0.01 to 0.48; P = 0.007; Fig. 7).
4. Discussion
Paracetamol and morphine have been commonly used for pain relief
[33-37]. Craig et al. compared intravenous paracetamol (1 g) with mor-
phine (10 mg) during 15 min in 55 patients with isolated limb trauma.
The pain score was recorded at 0, 5, 15, 30 and 60 min, and the results
found that the analgesic efficacy of intravenous morphine was compa-
rable to intravenous paracetamol at any time interval. The number of
rescue analgesia showed no statistically significance between two
groups, but morphine had higher incidence of complications than para-
cetamol [38]. These results were consistent with those when comparing
intravenous morphine (0.1 mg/kg) with paracetamol (1 g) for renal
colic pain [26].
However, Masosumi et al. found that intravenous acetaminophen
was significantly superior to morphine in terms of analgesic efficacy
for renal colic [24]. Our meta-analysis finds that intravenous paraceta-
mol is associated with significantly reduced pain scores at 30 min than
morphine for renal colic pain, but there is no statistical difference of
pain scores at 15 min and analgesic rescue between paracetamol and
morphine.
Several studies have reported morphine has higher incidence of ad-
verse events than acetaminophen when used for pain control, and these
adverse events include dizziness, hypotension, dry mouth, nausea and
vomiting [6,22,26]. In this meta-analysis, paracetamol has lower inci-
dence of dizziness than morphine for renal colic pain, but adverse
events including nausea and vomiting between two groups are compa-
rable. Regarding the sensitivity analysis, there is significant difference
for pain scores at 15 min. One gram intravenous paracetamol is com-
pared to 10 mg intravenous morphine or 0.1 mg/kg morphine among
included RCTs. Different methods of drugs may lead to the bias for the
pooling results.
Several limitations exist in this meta-analysis. Firstly, our analysis is
based on only five RCTs, and more RCTs with large sample size should be
conducted to explore this issue. Next, there is significant heterogeneity,
which may be derived from different methods of drugs and baseline
pain intensity. Finally, it is not feasible to perform the subgroup analysis
based on pain scores at long follow-up based on current studies.
5. Conclusion
Intravenous paracetamol may be superior to morphine in the control
of pain at 30 min for renal colic pain, and more studies should be con-
ducted to compare their analgesic efficacy and safety.

Fig. 6. Forest plot for the meta-analysis of nausea and vomiting.

Please cite this article as: X. Zhili, C. Linglong, J. Shuang, et al., Comparing the analgesic effect of intravenous paracetamol with morphine on
patients with renal colic..., American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.03.061
 X. Zhili et al. / American Journal of Emergency Medicine xxx (xxxx) xxx 5

Fig. 7. Forest plot for the meta-analysis of dizziness.

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Please cite this article as: X. Zhili, C. Linglong, J. Shuang, et al., Comparing the analgesic effect of intravenous paracetamol with morphine on
patients with renal colic..., American Journal of Emergency Medicine, https://doi.org/10.1016/j.ajem.2020.03.061