Comparison of the effectiveness of fentanyl versus morphine for severe postoperative pain management. A randomized, double blind, clinical trial

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r e v c o l o m b a n e s t e s i o l . 2 0 1 7;45(2):100–107
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Adriana Cadavid-Puentesa b, ,∗,Francisco José Bermúdez-Guerrero b,
Olga Giraldo-Salazar a b,, Fabio Mu ˜noz-Zapataa,Juan Otálvaro-Henaoa,
Juliana Ruíz-Sierra a,Julián Alvarado-Ramírez a,Gilma Hernández-Herrera a,
Daniel Camilo Aguirre-Acevedoa
aUniversidad de Antioquia. Medellín, Colombia
bUnidad de Dolor, Hospital San Vicente Fundación. Medellín, Colombia
a r t i c l e i n f o
Article history:
Received 11 February 2016
Accepted 8 November 2016
Available online 28 February 2017
Keywords:
Analgesics, opioid
Pain, postoperative
Fentanyl
Morphine
Randomized controlled trial
a b s t r a c t
Introduction: Intravenous rescue analgesia in the postoperative anesthesia care unit (PACU)
is the most effective method for reducing postoperative pain (POP) when perioperative mul-
timodal analgesia fails to control it. Appropriate analgesia during these first postoperative
hours may prevent morbidity associated with pain.
Objective: To compare the effectiveness of intravenous morphine versus fentanyl in the PACU
for reducing severe POP.
Methods: Randomized, prospective, double blind trial that included patients with severe POP
using VAS in the PACU. Rescue was performed on one group with 01 mg/kg morphine and
with another with 1mcg/kg of fentanyl every 5 min intravenously until pain was reduced
from severe to mild (VAS< 4). 30 patients were included in both groups.
Results: There were no significant differences in the percentage of patients with reduction
of severe POP to mild 5 min after the injection of morphine or fentanyl, or in the subsequent
rescue analgesia intervals (p> 0.05). Similarly, there were no significant differences in mean
VAS (95% CI) inmorphine or fentanyl groups beginning 5 min after the first analgesic dose
(p> 0.05) between the groups.
夽Please cite this article as: Cadavid-Puentes A, Bermúdez-Guerrero FJ, Giraldo-Salazar O, Mu ˜noz-Zapata F, Otálvaro-Henao J, Ruíz-Sierra
J, et al. Comparación de la efectividad del fentanilo versus morfina, en dolor severo postoperatorio. Ensayo clínico aleatorizado, doble
ciego. Rev Colomb Anestesiol. 2017;45:100–107.
∗Corresponding authorat: Calle 64 No. 51D–154, Unidad de Dolor, Hospital Universitario San Vicente Fundación, Universidad de Antioquia,
Medellín, Colombia.
E-mail address: adriana.cadavid@udea.edu.co (A. Cadavid-Puentes).
2256-2087/© 2016 Published by Elsevier Espa ˜na, S.L.U. on behalf of Sociedad Colombiana de Anestesiolog ´ıa y Reanimaci ´on. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

r e v c o l o m b a n e s t e s i o l . 2 01 7;45(2): 100–107 101
There were no significant differences in side effects such as respiratory depression, nausea,
vomiting or pruritus (p= 1.0). There was a high satisfaction in both groups (p>0.05).
Conclusions: Morphine and fentanyl were equally effective in treating severe POP after 5 min
and following intervals after rescue analgesia was initiated, during 25 min at PACU, with no
differences in efficacy or adverse effects between groups Register # NCT02145975 clinical-
trials.gov, prospective.
© 2016 Published by Elsevier Espa ˜na, S.L.U. on behalf of Sociedad Colombiana de
Anestesiolog´ıa y Reanimaci ´on. This is an open access article under the CC BY-NC-ND
license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Comparación de la efectividad del fentanilo versus morfina, en dolor
severo postoperatorio. Ensayo clínico aleatorizado, doble ciego
Palabras clave:
Analgésicos, opióides
Dolor posoperatorio
Fentanilo
Morfina
Ensayo clínico controlado
aleatorio
r e s u m e n
Introducción: La analgesia intravenosa de rescate en la unidad de cuidados postanestesicos
(UCPA), es la forma más efectiva de reducir el dolor POP, cuando la analgesia mutimodal
perioperatoria falla en controlarlo. Una adecuada analgesia en las primeras horas previene
la morbilidad asociada al dolor.
Objetivo: Comparar la efectividad para reducir eldolor POP severo de fentanilo versus morfina
en recuperación postanestésica.
Metodología: Estudio aleatorizado, prospectivo, doble ciego, en pacientes con dolor severo
POP medido con la escala EVA. El rescate se hizo con un grupo morfina a 0,1 mg/kg versus
fentanilo a 1 mcg/kg, cada 5 minutos, vía intravenosa, hasta reducir el dolor de severo a leve
(EVA <4). Se incluyeron 30 pacientes en el grupo morfina y 30 en el grupo fentanilo.
Resultados: No se observaron diferencias en porcentaje de pacientes con reducción del dolor
severo a leve desde los 5 minutos luego del rescate entre morfina o fentanilo, ó en los inter-
valos restantes (p > 0,05). Similarmente, no se encontraron diferencias significativas en la
media de EVA (IC 95%) desde los 5 minutos luego del rescate (p > 0.05) entre los grupos.
No hubo diferencias en efectos adversos como depresión respiratoria, náuseas, vómitos o
prurito entre grupos (p = 1,0). La satisfacción fue comparable en ambos grupos (p >0,05).
Conclusiones: La morfina y el fentanilo fueron igualmente efectivos para el rescate en dolor
severo desde los primeros 5 minutos, sin diferencias en los efectos adversos en ambos
grupos. Registro # NCT02145975 (clinicaltrials.gov,prospectivo).
© 2016 Publicado por Elsevier Espa˜na, S.L.U. en nombre de Sociedad Colombiana de
Anestesiolog´
ıa y Reanimaci ´
on. Este es un art´
ıculo Open Access bajo la licencia CC
BY-NC-ND (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction
Sever postoperative pain (POP) is a problem with high inci-
dence worldwide. Per a systematic literature review performed
by Dollin and collaborators, an incidence ofmoderate to severe
pain was found in 41% of patients in the postoperative period.
Of these, only 23% experience relief. 1In Latin America, severe
POP has been reported in 48% of surgical patients, and 51–60%
reported some level of pain these units.2,3In our Colombian
context, the situation is similar, with a prevalence of 22.3% of
severe static pain and 48.2% of dynamic pain.4These numbers
reflect insufficient management in postanesthetic care units
(PACU), also called postoperative care units.
The incidence, intensity and duration of postoperative
pain varies considerably among patients, types of surgical
intervention, hospitals, and even countries.5Pain related to
the postoperative period is not only important because it
for multiple organs.6In this way, stress because of pain
together with surgical trauma and previous morbidity of
the patient causes cardiovascular, 7,8gastrointestinal 6,9–11 and
respiratory12,13 dysfunction, among others. This increases the
incidence of myocardial ischemia, atelectasis (25–75% after
abdominal surgery), respiratory infection (pneumonia in 1–3%
of patients after heart surgery), ileus, deep vein thrombo-
sis, and cognitive dysfunction. In the same way, it has been
observed that pain increases PACU stay times and the number
of re-admittances through emergency for pain management.
In this way, patient recuperation is delayed and morbimortal-
ity increases along with the costs of patient care.7
It is important to note that in the PACUs, when we face
a patient with severe or unbearable pain, 14,15 the titration of
opioid analgesics is the most effective strategy for controlling
postoperative pain.16,17
The most studied and used opioid currently in PACUs for
analgesic rescue is morphine, which offers a good balance

causes suffering or unpleasant experiences to the patient
but also because of the damaging effects that it implies between the speed of the onset of action and the maintenance
of the analgesia due to its pharmacokinetic properties.18
102 r e v c o l o m b a n e s t e s i o l . 2 0 1 7;45(2):100–107
However, there are alternatives for analgesic titration, such as
fentanyl, which hasfavorable pharmacokinetics since theoret-
ically it has a faster analgesic response than morphine since it
is lipo-soluable, facilitating its passage across the blood–brain
barrier.19 Because ofthis, the relief of sever postoperative pain
in theory may be more rapid with options like fentanyl when
compared to morphine.15,16 The current study compares the
effectiveness of these two opioid analgesics against severe
postoperative pain at equipotent doses in 5 min intervals, the
time considered clinically relevant for the reduction of severe
pain in postoperative analgesia.
Materials and methods
With previous approval by the institutional Ethics Commit-
tee, an experimental, randomized, prospective, double blind
study was performed in which two potent analgesic opioids
were compared for severe postoperative pain, in the Hospital
Universitario San Vicente Fundación.
Patients with severe postoperative pain (VAS ≥7) in the
PACU were selected. Tw o groups were formed in the follow-
ing way: Group 1 was given intravenous morphine at a dose
of 0.1 mg/kg; Group 2 was given intravenous fentanyl at a
dose of 1 mcg/kg. As many doses as necessary were adminis-
tered every 5 min until pain was reduced from severe to mild
(VAS < 4).
The titration intervals were determined based on the work
of Grass and collaborators yielding an onset of action of fen-
tanyl of 4 min and 8 min for morphine with a variation of
onset of 3 min for the first drug and 5 min for the second.20
After the intravenous administration of morphine to anes-
thetized dogs, it was detected in the cerebrospinal fluid after
2–5 min and maximum concentrations were observed within
15–30 min.21 The primary outcome was to determine if the
analgesic rescue with fentanyl is more effective in reducing
severe POP (according to the VAS) in comparison with the
use of morphine in the PACU. Assuming a difference of 1.3
points in the averages of the VAS between the two groups
as clinically significant, with a standard deviation of 3 on the
VAS, a level of significance of 0.05 and a potency of 90%, the
required sample size is 22 participants per group. This was
increased by 20% for the possibility of losses, which would
be equivalent to a sample of 53 participants. We rounded
this up to 60 (30 per group). The calculation was performed
using the program STATA 10, and the patients were ran-
domly assigned into one of the two groups. Each group had
30 participants. All patients that complied with the inclusion
criteria were selected, these criteria being: age between 18
and 65 years, admitted for urgent or elective non-ambulatory
surgery under anesthesia and presenting severe postoper-
ative pain in the PACU, having undergone a preanesthetic
assessment, not being pregnant, not having a background
of hypersensitivity or allergic reactions to opioids, having
mental retardation, congenital, metabolic, hypoxic-ischemic
neurodegenerative states, or disorders related to aging that
would not allow for a proper evaluation on the visual analog
scale for pain assessment or a background of tolerance to opi-
oids due to chronic consumption (defined as the use of opioids
for a period longer than two weeks).
Procedure
Before recruitment of patients began, ameeting was held with
the nursing personnel and other auxiliary staff for surgical
services for their training in the purposes, reach, and forms
of implementation of the study so that it could be executed
properly. In this meeting, all of the ethical considerations and
the documentation corresponding to the clinical trial were
presented.
An implementation pilot test was performed before initi-
ating recruitment with 5% of the calculated sample to detect
faults in the different phases of the study and to correct them.
An analgesic dose was applied to eachpatient randomly. 60
numbers were randomized with a randomized number gener-
ator, with a minimum value of 1 and maximum value of 2.
30 envelopes were marked with the number 1 and 30 with
the number 2. A research assistant, who was not part of the
research group, put one of the analgesic guidelines into the
envelopes marked with the number 1 and put the other guide-
lines into the envelopes marked with the number 2. In this
way, the information about the medication to use, along with
the instructions for its preparation, were hidden. Next, the
envelopes were marked with the number from 1 to 60 in accor-
dance with the table of randomized numbers. As a patient
was selected, the guidelines that corresponded to him or her
by sequential order were applied by a nursing assistant of the
PACU who was not part of the study. In this way, the researcher
and the patient were unaware of the content of the medication
when it was applied. At the end of the study, the substances
used were revealed.
When the patient arrived to the recovery room, they were
evaluated with the visual analog scale for pain. If pain was
above 7, the envelope from the sequence was taken and
opened to assign the intervention. The opaque, sealed and
sequentially numbered envelopes were opened by a nurs-
ing assistant who was not part of the study. The envelopes
contained information about the medication that would be
applied to the corresponding patient with preparation instruc-
tions (morphine 10 mg in up to 10 ml of 0.9% saline, held in a
10 ml syringe, or 100 mcg fentanyl in up to 10 ml of 0.9% saline,
held in a 10 ml syringe). This paper with instructions was dis-
carded. The envelopes also contained a number (1 or 2) that
corresponded to one of the two interventions and that the
researcher recorded in the survey. In this way, the researcher
did not know which intervention had been applied. The nurs-
ing assistant applied the medication at a dose of 0.1ml/kg of
weight, following the researcher’s instructions. The medica-

signed the informed consent form for voluntary participation
in the study, and not having a risk of ASA >III, hypoxemia
(oxyhemoglobin saturation <90%), hemodynamic instabil-
ity, unexplained alteration of alertness due to anesthetic
effects, or basic neurological alterations due to psychiatric
disorders. These disorders could include anxiety disorders,
tion was prepared in identical syringes and at equi-analgesic
concentrations in accordance with protocol. After the admin-
istration of the medication, pain measurement was begun in
5min intervals inaccordance with the VAS. This was recorded
in a table and another dose of medication was administered
if pain was >3 until the patient manifested having a pain level
r e v c o l o m b a n e s t e s i o l . 2 01 7;45(2): 100–107 103
below 4 (mild pain, per the VAS). The total quantity of medi-
cation used in the intervention in ml was then recorded.
The sociodemographic data, type of surgery, and the dura-
tion of surgery were recorded. Also recorded was the time
spent in the recovery room in minutes.
Also, the presence of secondary effects from the opioids
was evaluated (hypotension, bradycardia, respiratory depres-
sion, nausea, vomiting, pruritus).
Furthermore, a Likert-Style Satisfaction Scale was used to
subjectively evaluate how satisfied each patient was with the
control of their postoperative pain as soon as the intervention
was started by giving a score of 1 to refer to complete satisfac-
tion, of 2 if they were simply satisfied, a score of 3 if they were
neither satisfied nor dissatisfied, and 4 if they were completely
dissatisfied.
Data analysis
The count of the categorical variables was reported in abso-
lute numbers and in percentages. The differences in the base
characteristics and post intervention variables were calcu-
lated with hypothesis testing. For qualitative variables, the
chi-squared test and Fisher’s exact test were used as appropri-
ate. The assumption of normality for the analysis ofoutcomes
was not fulfilled, so the Mann–Whitney test was used. The
base characteristics of both groups will be presented in a table
through measures of frequency and proportions forqualitative
variables and measures of central tendency and dispersion
for quantitative variables. In quantitative variables, normality
was evaluated with the Shapiro–Wilk test and group com-
parison with ANOVA. This analysis was supported with SPSS
software version 2.0.
Ethical aspects
The study complies with the Helsinki Declaration and the
norms in force in Colombia (Resolution No. 008430 of 1993 of
the Ministry of Health and Resolution No. 2378 of 2008 about
good clinical practice). No actions were taken that would not
comply with the ethical proposals recorded therein. An eval-
uation by the Ethics Committee of the University Hospital
where the study took place was required. The committee gave
their approval to proceed with the development of the study
and patients were asked individually to provide informed con-
sent.
Results
A total of 94 patients complied with the
selection
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of presenting severe pain in the PACU. Of
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Fig. 1 – Patient flow-diagram.
Source: authors.
(3 patients), vascular surgery (2 patients), and maxillofacial
surgery (2 patients). The majority were elective procedures,
with no statistically significant difference between the two
groups (p= 0.165).
30 patients were included in the morphine group and 30
patients in the fentanyl group. 26% (n= 8) versus 30% (n= 9) of
the patients in the morphine and fentanyl groups respectively
felt mild pain within 5 min of the first dose (p> 0.05). Similarly,
63% (n=19) versus 43% (n= 13) of the patients in the morphine
and fentanyl groups respectively felt mild pain after 10 min
(p> 0.05). In the following intervals, up to 25 min after the first
titration, no significant differences between the groups were
observed (Fig. 2).
The mean (95% CI) value for initial pain on the VASwas
7.8±1.1 and 8.1±1 in the morphine and fentanyl groups
respectively and5.4 ±2and 5.6 ±2.2 after 5 min in both groups.
After 10min, a mean VAS of 3.3±2.6 for the morphine group
and 3.7 ±2.7 in the fentanyl group was obtained (p>0.05). In
the following intervals, up to 25 min after the initial titration,
Table 1 – Sociodemographic characteristics of the
population.
Sociodemographic
characteristics
Group 1
Morphine
Group 2
Fentanyl
p-Value
Sex
Male 20 (66.6%) 18(60%) >0.05
Female 10 (33.3%) 12(40%)
Age (years) 39.7 ±
17.0 39.2 ±12.5 0.842
Weight (kg) 65.5 ±8.8 66.4±10.4 0.720

complied with the inclusion criteria and di
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(15 patients). There were also procedures o
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Weight (kg) 65.5 ±8.8 66.4±10.4 0.720
ASA classa0.573
I 14 (46.7%) 10(33.3%)
II 12 (40%) 15(50%)
III 4 (13.3%) 5(16.7%)
aClassificationsystem used by the American Society of Anesthesi-
ologists to estimate the risk for anesthesia based on the patients’
physical states.
Source: authors.
104 r e v c o l o m b a n e s t e s i o l . 2 0 1 7;45(2):100–107
Fig. 2 – Percentage of patients with mild pain (vas of 3 or less) in the morphine and fentanyl groups ( > 0.05).
Source: authors.
no significant differences in the mean VAS between the groups
was observed (Fig. 3).
Of the 60 patients analyzed, 59 reached the target pain level
(VAS < 4) with the analgesic titration. One patient of the mor-
phine group did not reach the target level, since he always
described the pain as severe (VAS > 7) after 9 doses (once every
5 min) of the medication.
With respect to the VAS after 5 and 10 min, the assump-
tions of normality and variance homogeneity were evaluated,
giving the result that the data in the two groups were
homogeneous. These results contrasted with an ANOVA of
repeated measures in which it was corroborated that no dif-
ferences existed between the study groups. Nevertheless, the
reduction of the average observed in the VAS scale after 5 min
and the VAS after 10 min in the two groups is due solely to
time and is independent of the type of opioid used (Fig. 3).
No significant difference was found in terms of the mean of
the accumulated dose of opioids to bring the pain from severe
to mild-moderate in the two groups (p= 0.701) or in the dura-
tion in minutes of the patients’ stay in the PACU (p= 0.260)
(Table 2).
No complications like hypotension, bradycardia, respira-
tory depression, or chest-wall rigidity. The incidence of nausea
and vomiting was 3.3% (1 patient) in the fentanyl group and
pruritus was experienced by 3.3% (1 patient) in the morphine
group, with no statistically significant differences between
them (p= 1).
Satisfaction with the analgesia treatments used in the
PACU was high, with no differences between the two groups
(Table 3).
Discussion
In this study, we found that fentanyl is comparable with mor-
phine in equipotent doses for the reduction of POPfrom severe
to mild-moderate levels as soon as 5min after titration. These

Fig. 3 – Comparison of the vas in response to morphine and
fentanyl ( = 0.531).
Source: authors.
results reiterate the utility of morphine, which continues to
be recommended for the treatment of severe POP due to its
high clinical evidence, greater experience of use,and pharma-
ceutical forms that allows for the establishment of a correct
titration. It also has a low economic cost, as described in other
studies. 21,22
In the literature, other comparisons of morphine and fen-
tanyl have been described previously for rescue analgesia.
However, in these cases the titration was not completed by
adjusting it to patient weight, 23,24 which can affect the anal-
gesic result if genetically determined variability of the opioid
requirements among patients is considered.25
r e v c o l o m b a n e s t e s i o l . 2 01 7;45(2): 100–107 105
Table 2 – Volume of analgesic mix applied and time of stay in PACU.
Study variable Group 1
Morphine
Group 2
Fentanyl
p-Value
Quantity of mix to bring pain from severe to mild (ml) 14.91 ±10.38 15.86 ±8.62 0.701
Stay in PACU (in
min) 97.87 ±21.65 117.11 ±29.19 0.260
Source: authors.
Table 3 – Degree of satisfaction with the analgesic agent used in the PACU.
Study variable Group 1
Morphine
Group 2
Fentanyl
p-Value
Completely satisfied 26(89.7%) 20(66.7%) a0.00001
Satisfied 2(6.9%) 7 (23.3%)
Neither satisfied nor unsatisfied 0 (0%) 3(10%)
Completely unsatisfied 1(3.4%) 0 (0%)
aWhen comparing theproportion of completely satisfied with completely unsatisfied.
Source: authors.
In our study, we observed that it was necessary to apply
more than one bolus injection of analgesia after 5min in most
of the patients to achieve a mild pain level in both groups of the
study. It was only possible to lower pain levels to mild with the
first dose of analgesia in 26% of the patients of the morphine
group and 30% of the patients of the fentanyl group. These
results are like the study of analgesic titration of Aubrun and
cols,21 where, at similar doses of morphine, patients required
3 applications in 5 min intervals to bring pain to mild levels
in 98% of patients. It is possible that the residual anesthesia
in recovery limits the response to a single analgesic doses,
since there is a greater risk of sedation with increased doses.
If this is the case, the process described by Aubrun—namely
comparing different titrations intervals—in his study of 1600
patients may be necessary. While a better response rate would
be expected after the first dose of analgesic, other titration
studies have not shown benefits of increasing the morphine
dose from 0.1 mg/kg to 0.15 mg/kg per bolus.26
Claxton and cols24 in a study performed at a hospital in
Toronto, Canada, compared the management of severe POP
with the use of morphine and fentanyl at fixed doses, with-
out calculating the doses per the physical characteristics of
the individuals. In our study, however, we performed the
comparison of equipotent doses adjusted for patient weight,
comparable to those used in the other studies. 27,28 This pro-
and its potential of more rapidly crossing the blood–brain bar-
rier, does not offer any advantage in POP analgesia measured
after5 min in comparison with equipotent doses of morphine.
After reviewing the potential danger of adverse effects,
some studies argue that nausea and vomiting appear to be less
frequent with the use of fentanyl.30–34 However, in other ones
these differences have not been evidenced,35 in our study, no
statistically significant differences were observed in the opi-
oids in terms of nausea and vomiting. That said, the only case
that presented this complication received fentanyl. A case of
pruritus was suffered by a patient from the morphine group.
Other adverse events associated with the use of opioids in
PACU were not reported.
Gender differences in the pain perception and in response
to treatment are well described in different studies.36,37 By
contrast, in our study, no important differences in the VAS
results were observed between the two intervention groups.
Our study does have limitations. One of them was that the
measurement of pain relief was not done continuously but in
5min intervals. While the pain relief after the application of
the rescue dosage is continuous, and it is possible that dif-
ferences could be seen before the 5-min mark in the opioids
subject to study, this measurement may also be affected by
the sedation that is frequent in patients in the PACU and is
even a result of the analgesia from the opioid administered. It

vides for a more adequate comparison of the two medications
and, as a result, a more clinically reproducible result.
One explanation of the comparable response in the per-
centage of patients with pain relief from morphine or fentanyl
that we observe in our study is to be found in previous
studies of the pharmacokinetic properties of morphine. In
experiments, when morphine was injected intravenously into
dogs, certain levels were detected in the cerebrospinal fluid
after 2–3min, and concentrations were also detected in the
cerebral tissue after 5 min.29 In clinical practice, Aubrun and
collaborators22 compared the best interval for the titration
of morphine between 5 min or 10 min in the PACU, report-
ing a higher percentage of pain relief, with no corresponding
increase in adverse effects, when morphine is applied in 4 min
intervals. It is believed that the greater lipophilicity of fentanyl
is estimated that 5 min after the application of the first dose
of analgesic, it is clinically significant to assess the analgesic
effectivity of an opioid and its potential advantage compared
toother options. In this trial, only two of themedications used
commonly against pain were study, but it would be possible
to choose other potent opioids.
Conclusions
Postoperative analgesic rescue with fentanyl or morphine in
equipotent doses is effective for reducing the time to reduce
pain from severe to mild, without important adverse effects
in either of the medications. In accordance with the findings
of this study, morphine—because of its safety profile—should
106 r e v c o l o m b a n e s t e s i o l . 2 0 1 7;45(2):100–107
continue to be the drug of choice in PACUs for the treatment
of severe postoperative pain.
Ethical disclosure
Protection of human and animal subjects. The authors
declare that the procedures followed were in accordance with
the regulations of the relevant clinical research ethics commit-
tee and with those of the Code of Ethics of the World Medical
Association (Declaration of Helsinki)
Confidentiality of data. The authors declare that they have fol-
lowed the protocols of their work center on the publication of
patient data.
Right to privacy and informed consent. The authors have
obtained the written informed consent of the patients or sub-
jects mentioned in the article. The corresponding author is in
possession of this document.
Funding
Universidad de Antioquia and Hospital Universitario San
Vicente Fundación.
Conflicts of interest
The authors have no conflicts of interest to declare.
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