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101

The Open Anesthesia Journal

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RESEARCH ARTICLE

Pulse-oximetry Derived Perfusion Index as a Predictor of the Efficacy of Rescue

Analgesia After Major Abdominal Surgeries
Ashraf Nabil Saleh1 , Raham Hasan Mostafa1,* , Ahmad Nabil Hamdy1,2 and Amr Fouad Hafez1
1
Department of Anaesthesia, Intensive Care and Pain Management, Ain Shams University, Cairo, Egypt
2
Department of Anaesthesia, Dubai Hospital, Dubai Health Authority, Dubai, United Arab Emirates

Abstract:
Study Objective:
The use of an easy to apply reliable tool is essential to assess pain in patients in intensive care units. This study aimed primarily to evaluate
perfusion index usefulness as an objective indicator of pain.

Methods and Measurements:

Data were collected from 40 non-intubated adult patients admitted to the surgical intensive care unit postoperatively. The Masimo pulse co-
oximetry perfusion index (PI) probe was attached to the patient. At the time of the first request for analgesia (T1), the Behavioural pain scale non-
intubated scoring system (BPS-NI) was recorded with the PI and patients' haemodynamics following which rescue analgesia was given. Thirty
minutes thereafter (T2), second measurements for the mentioned parameters were taken.

Main Results:
There was a statistically significant reduction in the BPS-NI score, blood pressure and heart rate after analgesic administration (P-values, <0.001,
0.039 and 0.001, respectively), together with a significant increase in the PI (P-value, 0.004). This means that the PI increases with adequate relief
from pain, as indicated by a decrease in BPS-NI score and haemodynamics, but the correlation was not statistically significant between their
changes.

Conclusion:
There was no statistically significant correlation between the PI and the pain score or other clinical indicators of pain either before or after the
administration of analgesic.

Keywords: Behavioural pain scale non-intubated, Major abdominal surgery, Masimo, Perfusion index, Postoperative pain, Pulse oximetry.

Article History Received: July 15, 2020 Revised: September 29, 2020 Accepted: October 07, 2020

1. INTRODUCTION and numeric rating scale (NRS) are used to assess pain
intensity postoperatively. In order to use these scales, patients
In the Intensive care unit (ICU), pain is usually
need to be able to understand what is said to them and express
underestimated due to the difficulty of its assessment in themselves. But this cannot be carried out for individuals with
critically ill patients. It can evolve from many sources, for e.g., communication problems [2]. Also, the use of haemodynamic
postoperative surgical incisions, penetrating chest tubes, and changes has been demonstrated to be neither valid nor reliable
even ICU procedures as bedside debridement. It was shown as it is affected by many other aetiologies, and guidelines
that alleviating pain effectively in both intubated and non- recommend that vital signs should not be used to evaluate pain
intubated ICU patients has been associated with improved in ICU patients [3]. This phenomenon has led to the
outcomes [1]. Scales such as the Visual analogue scale (VAS) construction of categorical and numerical methods of pain
*
assessment in critically ill patients. The behavioural pain scale
Address correspondence to this author at the Department of Anaesthesia,
(BPS) -whether intubated or non-intubated forms- has been
Intensive Care and Pain Management, Ain Shams University, El-hay El-Sabee,
Nasr City, Cairo, Egypt; Tel: 002/01222530020; reported as a valid and reliable tool for pain assessment in ICU
E-mail: [email protected] patients with recommendations of its use to assess the presence

DOI: 10.2174/2589645802014010101, 2020, 14, 101-107

102 The Open Anesthesia Journal, 2020, Volume 14 Saleh et al.

of pain in adult ICU patients when self-reporting is not possible status and unconscious patients were also excluded. Patients
[4]. But unfortunately, the use of Behavioural pain scale non- who had combined general epidural anaesthesia or Transversus
intubated scoring system (BPS-NI) scale requires sustained abdominis plane block were also excluded.
efforts to educate and train the ICU team regarding the scale
because of its subjective nature [5]. Also, BPS-NI is time- 2.1. Patients’ Postoperative Interventions and Management
consuming with multiple points of assessment, making it non- After extubation and full recovery, patients were admitted
practical [6]. The need for simple, non-invasive, rapid, and to ICU. Standard monitors were applied: an Electrocardiogram,
objective tools for pain evaluation represents a present gap in pulse oximeter, and non-invasive arterial blood pressure
the literature. The Masimo device could be a promising indirect monitor, and all baseline readings were recorded. All patients
tool for pain assessment. The Masimo set pulse oximetry received nasal oxygen (4 L/min). The oximeter probe
system can measure the perfusion index (PI) at the monitored (Radical-7®, Masimo Corporation, Irvine, CA, USA) used to
site by calculating the relation between pulsatile and static monitor the PI was attached to the middle fingertip of the hand
blood in peripheral tissues. In contrast to the conventional and was wrapped in a towel to decrease heat loss. The patients
pulse oximeter which measures O2 saturation, Masimo Signal were kept warm with wool blankets, warm i.v. fluids, and a
Extraction Technology depends upon the amount of blood at warm air-forced device. All patients were observed until they
the monitoring site, not upon blood oxygenation. Therefore, PI asked for rescue analgesia. Sedation was assessed by
is considered as an indirect, non-invasive, and continuous Richmond agitation-sedation scale score (RASS) that was
measure of peripheral perfusion. It ranges from 0.02% (very recorded at specific timings: on arrival to ICU, and after 1 and
weak pulse strength) to 20% (very strong pulse strength) [7]. 2 hours from arrival to ICU [9]. The RASS is a 10- point
Pain induces vasoconstriction due to sympathetic nervous validated sedation scale with 4 levels for agitation, 5 levels for
system stimulation with a subsequent decrease in PI [8]. This sedation, and 1 level for calm, awake patients. The scale’s
direct relation between pain and sympathetic stimulation raises anchor is centered at 0 (alert and calm) [9]. Our intensive care
the hypothesis that the PI can be used as an indirect objective unit analgesia protocol in general is 1 g i.v. paracetamol
tool for pain assessment. The current study aimed primarily to repeated every 6 h and 5 mg Nalbuphine increments upon
evaluate the correlation between perfusion index and other patients’ request or if Behavioural pain scale non-intubated
clinical indicators of pain after rescue analgesia administration
scoring system (BPS-NI) ≥ to 5, to whatever 1st occurred. Pain
and so detecting its usefulness as an objective indicator of pain
assessment in this study was achieved by Behavioural pain
assessment in ICU.
scale non-intubated scoring system [6]. The BPS-NI evaluates
three behavioural domains (i.e., facial expression, movements
2. METHODS AND MEASUREMENTS
of upper limbs and vocalization). Each domain contains four
All procedures performed in studies involving human descriptors that are rated on a 1–4 scale, and the total BPS
participants were in accordance with the ethical standards of value can range from 3 (no pain) to 12 (most pain). The
the institutional research committee and with the 1964 Helsinki procedure for using the BPS is estimated to take minimal time
Declaration and its later amendments or comparable ethical (2–5 minutes). Because each domain of the BPS-NI contains
standards. The work was approved by the Ethics committee of four descriptors, it has the advantage of avoiding a possible
Ain Shams University hospital (FMASU R 05/ 2019) on observer bias that is described as when an observer rates
23/1/2019. The study was prospectively registered with Pan preferentially the middle item of a three-point scale [6]. At the
African Clinical Trial Registry (PACTR) with Registration time of the first request for analgesia (T1), Behavioural pain
Number PACTR201901839969911 in accordance with WHO scale non-intubated scoring system (BPS-NI) was recorded
and ICMJE standards. Written informed consent was obtained together with the PI, heart rate (HR), mean arterial blood
from all subjects or their legal surrogate. pressure (MAP), peripheral oxygen saturation, and axillary
This is a prospective observational study that was temperature, following which 5 mg Nalbuphine and 1 gram
conducted in Ain Shams university hospital intensive care unit paracetamol were given. Thirty minutes after postoperative
through the period from January 2019 to October 2019. The analgesia (T2), second measurements for the mentioned
study comprised 40 patients. Eligibility criteria for this study parameters were taken. We considered the following criteria as
included patients with American Society of Anaesthesiologists indicators of pain relief: a 100% increase of PI value from
(ASA) physical status I to III, of either sex, 18-80 years of age, baseline.
non-sedated non-intubated patients that were admitted
2.2. Data Collection
postoperatively to ICU after major abdominal surgery. We
categorized the participants into two “age groups” according to The required sample size was calculated using the
age: an elderly group (> 60 years) and a young group (< 60 G*Power software v. 3.1.9.4 [10]. The primary outcome
years). Then we further classified each “age group” into a male measure was the correlation between the change in PI and the
group and a female group. Now we had a total of 4 groups: an change in pain score as assessed using the BPS-NI. We
elderly male group (> 60 years) = OM group, an elderly female considered that a correlation coefficient of 0.45 would be of
group (> 60 years) = OF group, a young male group (< 60 clinical value. So, assuming an alpha error of 0.05, we
years) = YM group and a young female group (< 60 years) = calculated that a sample size of 40 patients would be required
YF group. Exclusion criteria involved patients with fever, to achieve a power of 85% to detect statistical significance for
hypothermia, history of a neurological, psychiatric, dementia or a correlation coefficient of 0.45 between the change in PI and
chronic pain disorder. Patients with unstable haemodynamic change in pain score. Data were analysed using IBM© SPSS©
Perfusion Index: A Predictor of Rescue Analgesia Efficacy The Open Anesthesia Journal, 2020, Volume 14 103

Statistics version 23 (IBM© Corp., Armonk, NY). Categorical indicators of pain before and after analgesic administration.
variables were presented as number and percentage. Normally There was a statistically significant reduction in the BPS-NI
distributed numerical variables were presented as mean and score, MAP and heart rate after analgesic administration (P-
standard deviation and intergroup differences were compared values, <0.001, 0.039 and 0.001, respectively). On the other
using the unpaired t-test. The paired t-test was used to compare hand, there was a statistically significant increase in the PI after
normally distributed paired data. Non-normally distributed analgesic administration (P-value, 0.004). Regarding the
numerical variables were presented as median and interquartile difference in axillary temperature, there was no statistically
range and intergroup differences were compared using the significant difference between the measured axillary
Mann-Whitney U-test. The Wilcoxon signed ranks test was temperature at T1 and that at T2 (P-value, 0.442). There was no
used to compare non-normally distributed paired data. statistically significant correlation between the PI and the pain
Correlations were tested using the Spearman rank correlation. score or other clinical indicators of pain either before or after
Multivariable linear regression was used to examine the effect administration of analgesic. There was no statistically
of age or sex on the change in PI after analgesic administration. significant correlation between the change in PI and the change
The PI was subjected to logarithmic transformation prior to in pain score or other clinical indicators of pain (Table 3).
entry into regression because of marked skewness of its Studying the correlation of PI with other clinical variables
frequency distribution. Two-sided P-values <0.05 were before and after administration of analgesic showed a weak
considered statistically significant. inverse correlation between the PI after administration of
analgesic and the RASS score at 1 h (rho, -0.378; P-value,
3. RESULTS 0.016) and moderate inverse correlation between the change in
PI and the RASS score at 1 h (rho, -0.409; P-value, 0.009).
We studied 40 age-matched patients, 20 males and 20
There was no statistically significant relationship between the
females, with a mean ± SD age of 48 ± 19 years. The
age or sex and the PI either before or after the administration of
characteristics of the study population and operative details are
analgesic. Neither there was a statistically significant
shown in Table 1.
relationship between the change in PI and the age or sex (Table
Table 2 shows a comparison of pain score, PI and other 4).

Table 1. Characteristics of the study population.

Variable Value
Sex
F 20 (50.0%)
M 20 (50.0%)
Age (years) 48 ± 19
Age category
≤60 yr. 20 (50.0%)
>60 yr. 20 (50.0%)
Weight (kg) 73 ± 15
ASA-PS
ASA-PS I 6 (15.0%)
ASA-PS II 18 (45.0%)
ASA-PS III 16 (40.0%)
Surgical procedure
Abdominal wall debridement 2 (5.0%)
Aortobifemoral bypass 1 (2.5%)
Appendectomy 6 (15.0%)
Bariatric surgery 1 (2.5%)
Colon resection 2 (5.0%)
Drainage of renal abscess 1 (2.5%
Exploration laparotomy 16 (40.0%)
Intestinal resection and anastomosis 2 (5.0%)
Pancreatic resection with triple bypass 1 (2.5%)
Perforated DU repair 1 (2.5%)
Radical cystectomy 1 (2.5%)
Rectovesical fistula repair 1 (2.5%)
Splenectomy 2 (5.0%)
Strangulated hernia repair 2 (5.0%)
Open prostatectomy 1 2.5%
104 The Open Anesthesia Journal, 2020, Volume 14 Saleh et al.

7DEOH 1FRQWG

Operative time (hr) 2.5 ± 1.1

Volume of transfused blood (ml) 0 (0 to 350)
Intraoperative opioid dosage (mg of morphine equivalent) 15 (15 to 20)
TFA request (min) 35 (10 to 60)
Data are number (%), mean ± SD or median (interquartile range).
ASA-PS; American Society of Anaesthesiologists - physical status, DU; Duodenal ulcer, F; female, M; Male, TFA; Time of the first request of analgesia.

Table 2. Comparison of pain score, PI and other indicators of pain before and after analgesic administration.

Variable Before analgesia After analgesia P-value*

BPS-NI score 6 (4 - 7) 4 (3 - 5) <0.001
PI 1.15 (0.64 - 2.05) 1.45 (0.99 - 3.45) 0.004
MAP (mmHg) 86 (62 - 99) 79 (61 - 95) 0.039
HR (bpm) 100 (84 - 116) 96 (75 - 116) 0.001
Axillary temperature (°C) 37.1 ± 0.5 37.1 ± 0.5 0.442§
SpO2 (%) 98 ± 2 98 ± 3 0.107§
Data are median (interquartile range) or mean ± SD.
*Wilcoxon signed ranks test unless otherwise indicated.
§Paired-samples t-test.
BPS-NI; Behavioral pain scale non-intubated scoring system, HR; Heart rate, MAP; Mean arterial blood pressure, PI; Perfusion index, SpO2; Oxygen saturation.

Table 3. Correlation of PI with pain score and other clinical indicators of pain before and after administration of analgesic.

Before analgesic PI
Variable rho P-value
BPS-NI 0.177 0.276
MAP 0.198 0.221
HR 0.261 0.104
Axillary temperature 0.101 0.536
SpO2 -0.088 0.596
After analgesic PI
Variable rho P-value
BPS-NI -0.002 0.989
MAP 0.049 0.763
HR 0.291 0.069
Axillary temperature -0.215 0.188
SpO2 -0.061 0.713
Change Δ PI
Variable rho P-value
Δ BPS-NI -0.130 0.425
Δ MAP -0.116 0.474
Δ HR 0.285 0.075
Δ Axillary temperature -0.248 0.128
Δ SpO2 -0.103 0.534
Rho = Spearman rank correlation coefficient.
BPS-NI; Behavioral pain scale non-intubated scoring system, HR; Heart rate, MAP; Mean arterial blood pressure, SpO2; Oxygen saturation, Δ means change in parameter

Table 4. Relationship between PI and age category or sex.

PI
Before analgesic Variable Median Interquartile range P-value*
Age category ≤60 yr. 1.30 0.70 to 3.45 0.323
>60 yr. 0.93 0.64 to 1.35
Sex M 1.10 0.79 to 1.65 0.924
F 1.25 0.58 to 3.10
Perfusion Index: A Predictor of Rescue Analgesia Efficacy The Open Anesthesia Journal, 2020, Volume 14 105

7DEOH 4FRQWG

PI
After analgesic Variable Median Interquartile range P-value*
Age category ≤60 yr. 1.75 0.85 to 4.50 0.675
>60 yr. 1.30 1.05 to 2.60
Sex M 1.60 1.10 to 2.30 0.925
F 1.40 0.85 to 4.20

Δ PI
Change Variable Median Interquartile range P-value*
Age category ≤60 yr. 0.30 -0.25 to 1.30 0.695
>60 yr. 0.38 0.05 to 0.89
Sex F 0.38 -0.01 to 1.30 0.797
M 0.35 -0.05 to 0.74
*Mann-Whitney test.
F; female, M; Male

Table 5. Multivariable regression analysis for the effect of age or sex on the change in PI (Δ PI) with adjustment for other
confounding factors.

95% CI for B
variable B SE Beta t P-value Lower Bound Upper Bound
(Constant) -0.750 0.567 -1.322 0.200 -1.927 0.427
Male sex (=1) † 0.176 0.246 0.169 0.716 0.482 -0.334 0.685
Age >60 yr.‡ -0.337 0.297 -0.322 -1.135 0.269 -0.953 0.279
ASA-PS II (=1) § 0.037 0.333 0.035 0.110 0.913 -0.654 0.727
ASA-PS III (=1) § 0.034 0.445 0.030 0.077 0.939 -0.888 0.956
Operative time (h) -0.006 0.120 -0.012 -0.048 0.962 -0.255 0.244
Intraoperative opioid dosage (mg morphine equivalent) 0.039 0.034 0.311 1.134 0.269 -0.032 0.110
B = unstandardized regression coefficient, SE = standard error, Beta = standardized regression coefficient, 95% CI = 95% confidence interval.
† Referenced to female sex (=0).
‡ Referenced to age ≤60 yr. (=0).
§ Referenced to ASA-PS I (=0).
ASA-PS American Society of Anaesthesiologists physical status

Table 5 shows the results of multivariable regression behaviour scales are very difficult, require training of the ICU
analysis for the effect of age or sex on the change in PI (Δ PI) staff and are time-consuming [11]. There are multiple studies
with adjustment for other confounding factors. After exploring the relationship between PI and pain, whether in
adjustment for the effect of American Society of awake patients [12, 13] or those under general anaesthesia [8].
Anaesthesiologists - Physical Status, operative time and And they all proved that PI decreased due to painful stimulus.
intraoperative opioid consumption, there was no statistically On the other hand, other studies explored the relationship
significant relationship between the change in PI and the between PI and analgesia whether under general anaesthesia [2,
patient’s age (P-value, 0.269) and sex (P-value, 0.482). 11, 14] or epidural analgesia [15] or transforaminal block [16].
And they all proved that PI increased after analgesic
4. DISCUSSION
administration. All of these studies explored different types of
In our study, there was a statistically significant increase in pain as postoperative surgical pain [2, 11, 14, 15], intensive
the PI after analgesic administration. Also, there was a care procedural pain [13], electric stimulation pain [8, 12] and
statistically significant reduction in the BPS-NI score, MAP finally, chronic radicular pain [16].
and heart rate after analgesic administration. But, we did not
find any statistically significant correlation between the In agreement with the current study, Tapar and colleagues
absolute value of “PI and other examined clinical pain [2] showed that there was a statistically significant difference
indicators (the BPS-NI, MAP, and HR)” before or after rescue between pre-analgesic and post-analgesic PI, VAS scores and
analgesia administration as well as with their changes. The haemodynamics with no correlation between PI absolute values
relationship between analgesia and PI is the basis of our & VAS scores absolute values at pre- and post-analgesic
hypothesis in this study. The PI is a non-invasive and easy measurements. Also, there was a detected weak negative
method that can be used for evaluating pain and monitoring the correlation between the change in PI and the change of pain
effectiveness of analgesia. It can also eliminate psychological score (VAS score). It was a prospective observational study
factors such as fear, anxiety, depression, and anger [11]. This that was done on 89 patients that had undergone minor to
benefit can be more valid in patients suffering from cognitive moderate surgical procedures and were observed in Post
impairment and dementia especially because common pain Anesthesia Care Unit (PACU) postoperatively. They used
106 The Open Anesthesia Journal, 2020, Volume 14 Saleh et al.

morphine increments for post-operative analgesia and the upon activation of the epidural blockade with 10 mL 0.25%
subjective pain score used was VAS score. Another study bupivacaine, the PI increased. Also, they noticed a gradual
confirming our findings was carried out by Mohammed and decrease in PI with a fade of epidural analgesia (manifested by
colleagues [11], in which a Masimo pulse co-oximetry a gradual increase in labor pain). They concluded that PI could
perfusion index was attached to 70 American Society of offer a non-invasive option to objectively assess pain
Anaesthesiologists-Physical Status I adult patients at PACU, perception and this is in accordance with our study findings.
who underwent lumbar spine discectomy. The PI was But in opposition, there was a significant negative association
significantly higher at post-analgesic timing than at pre- between PI and VAS absolute values at the 10th, 30th, 60th
analgesic timing. This increase was associated with a minutes and 2nd hour after epidural blockade activation. Also,
statistically significant decrease in other measured parameters. there was a significant negative association between PI and HR
This means that the PI increases with adequate relief from pain, absolute values before the procedure and at the time of
as indicated by a decrease in VAS, HR, and MAP. A decrease administration of epidural analgesia and 5 minutes later. They
in VAS was associated with an increase in PI, but the noted that perfusion index had no significant correlation with
correlation was not statistically significant. Also, the both systolic and diastolic blood pressures.
correlation between change in PI and change in VAS score &
Few studies had explored the effect of age or sex on the
change in MAP was not statistically significant and this is
change in PI after analgesic administration or painful
consistent with our study. It is to be noted that there was a
stimulation. In the current study, there was no statistically
statistically significant negative correlation between change in
significant relationship between the age or sex and the PI either
HR and change in PI. For all patients, analgesia was achieved
before or after the administration of analgesic. Neither was
with i.v. morphine and i.v. 1 g paracetamol and subjective pain
there a statistically significant relationship between the change
scale used was the VAS score. In correspondence to the current
in PI and the age or sex. Supporting our findings, Chu and
study, Nishimura and colleagues [12] studied the changes in
colleagues [14] stated the same findings in their study. On the
perfusion index in response to noxious electrical stimulation in
other hand, Nishimura and colleagues [12] observed that the
awake healthy subjects. They measured the PI and pulse rate in
old women group did not show any changes in PI before or
70 healthy volunteers exposed to increasing electrical
after electrical stimulation when compared to other age and sex
stimulation until they reached their pain tolerance threshold.
groups that showed a decrease in PI.
They observed a significantly decreased PI in response to
electrical stimulation but with no increase in the pulse rate due
5. LIMITATION
to its very small intensity. They concluded that the PI may be
an independent parameter reflecting the perception of noxious PI measurements are very sensitive to patients’
stimuli and offers a non-invasive option for objectively movements. The rapid fluctuation and sensitivity of PI are its
evaluating pain perception. Finally, in a study done by Hasanin weakness as well as strength in the clinical field. To
and colleagues [13], they reported a difference between PI compensate for this limitation, PI monitoring should be done
values, Systolic blood pressure, Diastolic blood pressure, HR, after ensuring position stability.
and pain intensity before and after the pain created by
positioning in ICU patients. BPS-NI has been used for CONCLUSION
subjective pain assessment especially as all patients were Perfusion index can be added to other indicators of pain
sedated (but not-intubated), which might affect their assessment in ICU. It is easy, non-invasive, free of subjective
communication with the medical staff. There was a significant interpretation, less time-consuming and finally, not affected by
increase in the Systolic blood pressure, Diastolic blood age or sex related factors.
pressure, heart rate and BPS-NI post-positioning values
compared with pre-positioning values. Also, a significant ETHICS APPROVAL AND CONSENT TO
decrease in PI was also observed at post-positioning values PARTICIPATE
compared with pre-positioning values. Also, no correlation was
found between the PI values and any other variable (Systolic All procedures performed in studies involving human
blood pressure, Diastolic blood pressure, HR, and BPS-NI) participants were in accordance with the ethical standards of
before or after the patient positioning. Hasanin’s study differs the institutional research committee and with the 1964 Helsinki
from the current study in that the change in BPS-NI showed a Declaration and its later amendments or comparable ethical
good correlation with the change in PI. On the other hand, standards. The work was approved by the Ethics committee of
there are two studies which showed a weak correlation between Ain Shams University hospital (FMASU R 05/ 2019) on
different parameters. In a retrospective observational study 23/1/2019. The study was prospectively registered with Pan
done by Chu and colleagues [14], the correlation between the African Clinical Trial Registry (PACTR) with Registration
PI and VAS score together with their delta change and their Number PACTR201901839969911 in accordance with WHO
percentage change showed weak correlations. They enrolled 80 and ICMJE standards.
female patients postoperatively, with a different age range, who
HUMAN AND ANIMAL RIGHTS
were observed in PACU before and after intravenous morphine
analgesic administration. The second study was done by Kupeli No Animals were used in this research. All human research
& Kulhan [15]. They investigated the relationship between procedures followed were in accordance with the ethical
labour pain level and PI in 30 women undergoing spontaneous standards of the committee responsible for human
vaginal delivery under epidural analgesia. They noticed that experimentation (institutional and national), and with the
Perfusion Index: A Predictor of Rescue Analgesia Efficacy The Open Anesthesia Journal, 2020, Volume 14 107

Helsinki Declaration of 1975, as revised in 2013. [http://dx.doi.org/10.1097/j.pain.0000000000000834] [PMID:

28362678]
[5] Chanques G, Tarri T, Ride A, et al. Analgesia nociception index for
CONSENT FOR PUBLICATION the assessment of pain in critically ill patients: a diagnostic accuracy
study. Br J Anaesth 2017; 119(4): 812-20.
Written informed consent was obtained from all subjects or
[http://dx.doi.org/10.1093/bja/aex210] [PMID: 29121287]
their legal surrogate. [6] Chanques G, Payen JF, Mercier G, et al. Assessing pain in non-
intubated critically ill patients unable to self report: an adaptation of
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[http://dx.doi.org/10.1007/s00134-009-1590-5] [PMID: 19697008]
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funding agencies in the public, commercial, or not-for-profit Sedation Scale: validity and reliability in adult intensive care unit
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We have no affiliations with or involvement in any [http://dx.doi.org/10.4103/2356-9115.172783]
organization or entity that we may have any financial interests [12] Nishimura T, Nakae A, Shibata M, Mashimo T, Fujino Y. Age-related
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