Evaluation of pain and physiological stress during targeted neonatal echocardiography

Abstract

BACKGROUND:

Targeted neonatal echocardiography (Tn-Echo) is a non-invasive examination which may cause pain/discomfort and physiological instability in neonates, but there is little evidence for the same. We conducted this study to evaluate whether targeted neonatal echocardiography causes pain or physiological stress to newborn infants.

METHODS:

This cross-sectional study was conducted in a tertiary level NICU. Neonates undergoing targeted neonatal echocardiography were enrolled in this study. Pain was assessed using Premature Infant Pain Profile-Revised (PIPP-R) score before, during and after targeted neonatal echocardiography examination. Heart rate, oxygen saturation, perfusion index and blood pressure were also recorded at the same time points.

RESULTS:

A total of 88 neonates were enrolled. Mean (SD) PIPP-R score during Tn-Echo was 8.18 (2.6) versus 3.60 (1.8) and 4.24 (2.0) before and after respectively (p value < 0.001). Heart rate and respiratory rate were significantly higher during targeted neonatal echocardiography; oxygen saturation and perfusion index were significantly lower during targeted neonatal echocardiography. Preterm infants had higher PIPP-R score compared to term neonates before, during and after the Tn-Echo [8.76 (2.4) versus 6.81 (2.4); p value < 0.001].

CONCLUSION:

Targeted neonatal echocardiography causes significant pain/discomfort and physiological instability in neonates.

Keywords

Neonate pain physiological stress PIPP-R targeted neonatal echocardiography

1 Introduction

High risk neonates requiring admission to intensive care units undergo multiple procedures. Evidence suggests that most of these procedures cause pain leading to physiological stress. Even routine care practices can cause stress to neonates, especially when preterm. Chronic exposure to stress and pain may alter brain development and may contribute directly or indirectly to developmental impairments [1].

Scientific literature in recent years has affirmed that neonates, especially when premature, are more sensitive to nociceptive stimuli than older children. Neonates in the intensive care unit experience up to 16 painful procedures a day, especially in the first two weeks of admission [2]. Unmanaged pain has immediate consequences such as alterations in hemodynamic stability and altered stress hormone expression and long-term negative effects such as allodynia, heightened peripheral sensitivity, altered pain reactivity that persist even after NICU discharge [3, 4]. Sensitivity towards neonatal pain among neonatologists has increased in the last decade. Non-pharmacological and pharmacological measures of reducing or preventing pain are mainly used for acute procedural pain like heel lance, suctioning or intravenous catheter placement.

In the last decade, targeted neonatal echocardiography (Tn-Echo) is being used more frequently for bedside assessment of cardiovascular and hemodynamic status and has become the standard of care in most tertiary neonatal intensive care units. Being a non-invasive procedure, its potential to cause discomfort or stress has not received much attention. There is limited evidence in literature to quantify how much pain or discomfort Tn-Echo causes. Hence we conducted this cross-sectional study in our unit to evaluate whether Tn-Echo causes any physiological stress and/ or pain.

2 Materials and methods

This was a cross-sectional study conducted from October 2020 to February 2021 in a tertiary care NICU after obtaining approval of the institutional ethics committee (IEC/56/20). All neonates warranting a Tn-Echo during the study period were screened for eligibility for inclusion in the study. Parents were informed about the need for a Tn-Echo. They were informed about the study methodology which included recording a video of the baby’s facial expressions before, during and after the Tn-ECHO in order to look for discomfort, if any, as a part of the pain assessment score. Infants were included in the study after a written informed consent was obtained from parent/s. Neonates with APGAR score < 3 at 5 minutes, neonatal encephalopathy, major congenital malformations and neonates receiving drugs causing CNS depression were excluded from the study.

2.1 Procedure

The decision to perform Tn-Echo was taken by the clinical team for the following indications - to assess hemodynamically significant patent ductus arteriosus, to evaluate cardiac function and preload in neonates with shock, to evaluate neonates with suspected persistent pulmonary hypertension of the newborn or to screen for critical congenital cardiac anomalies. Tn-Echo examination was done by a senior neonatologist trained in basic neonatal echocardiography using Sonosite Fujifilm 2D-Echo machine and pre-warmed jelly. It was ensured that no interventions were done for 30 minutes before the examination and all noxious stimuli were minimized.

Premature Infant Pain Profile- Revised (PIPP-R) score was used for assessing pain in these neonates [5]. To assess the behavioural score component of PIPP-R, facial expressions of the neonate were recorded on a video device for 30 seconds duration 10 minutes before, throughout the Tn-Echo examination and for 30 seconds duration 10 minutes after the examination. The highest score anytime during the Tn-Echo examination was recorded in each domain. Physiological parameters - heart rate, respiratory rate, oxygen saturation (SpO₂) and perfusion index- were recorded 10 mins prior to examination, 10 minutes through the examination and 10 minutes after the Tn-Echo examination. Highest heart rate, lowest SpO₂ and perfusion index during these periods were recorded for the purpose of assessing PIPP-R. Heart rate, perfusion index and SpO₂ were recorded with Masimo Radical-7 pulse oximeter. Blood pressure was recorded with Philips GoldwayUT-6000A machine, using an appropriately sized neonatal cuff 10 minutes prior and 10 minutes after examination, but was not recorded during Tn-Echo examination.

Primary outcome was the pain/discomfort experienced by the neonates as evidenced by PIPP-R score before, during and after the Tn-Echo examination. Secondary outcomes were the changes in the physiological parameters like heart rate, respiratory rate, SpO₂ and perfusion index before, during and after the Tn-Echo examination. Other secondary outcomes studied were comparison of PIPP-R scores and physiological parameters between term and preterm neonates.

2.2 Sample size and statistical analysis

All eligible neonates satisfying the inclusion criteria were consecutively enrolled during the 5 months study period after obtaining parental consent. Statistical analysis was done using SPSS software (version 25.0). Categorical variables were expressed as frequency and proportion. Continuous variables were expressed as mean and standard deviation or median (IQR). Comparison between the groups for discrete variables was done using Chi square test/Fischer’s exact test. For continuous variables, ANOVA was used for analysing statistical significance in the three groups (before, during and after procedure groups). P value of < 0.05 was considered as statistically significant.

3 Results

A total of 97 neonates underwent Tn-Echo during the study period. Eighty-eight neonates were enrolled in this study, nine neonates were excluded because five neonates had perinatal asphyxia with hypoxic-ischemic encephalopathy, three neonates were on sedation and parents of one neonate were not available for consent (Fig. 1). The baseline characteristics of neonates undergoing the Tn-Echo are depicted in Table 1. Of these 88 neonates, 58 (65.9%) underwent Tn-Echo for patent ductus arteriosus screening. 5 (5.7%), 8 (9.1%) and 17 (19.3%) neonates underwent Tn-Echo for screening of critical congenital heart disease, persistent pulmonary hypertension (PPHN) and cardiac function and preload assessment in cases of shock respectively.

Fig. 1

Enrolment of infants undergoing Tn-Echo for assessment of PIPP-R scores.

Table 1

Baseline characteristics of neonates undergoing Tn-Echo

Characteristics	Value (N = 88)
Birth weight, g, Mean(SD)	1758 (844)
Gestational age, weeks, Mean(SD)	33.4 (4.3)
Male, n(%)	47 (53.4)
Preterm infants, n(%)	55 (62.5)
Age at procedure, h, Median(IQR)	35.5 (18,77.7)
Neonates on non invasive ventilation, n(%)	36 (40.9)
Neonates on invasive ventilation, n(%)	21 (23.8)

Mean (SD) PIPP-R score during the examination was 8.18(2.6) versus 3.60(1.8) and 4.24 (2.0) before and after the Tn-Echo examination (p < 0.001) which suggested that neonates experienced mild to moderate pain during the Tn-ECHO. All the components of PIPP-R score were higher during the procedure compared to before and after (Table 2).

Table 2

PIPP-R score with its components and the physiological parameters before, during and after the Tn-Echo

I. Components of PIPP-R score	Before Tn ECHO	During Tn ECHO	After Tn ECHO	P value
a) Sub-score of change in heart rate component of PIPP-R, mean (SD)	0.33 (0.5)	1.11 (0.6)	0.48 (0.5)	< 0.001
b) Sub-score of change in SpO2 component of PIPP-R, mean (SD)	0.15 (0.4)	0.86 (0.6)	0.26 (0.5)	< 0.001
c) Sub-score of brow bulge component of PIPP-R, mean (SD)	0.26 (0.4)	1.56 (0.7)	0.49 (0.5)	< 0.001
d) Sub-score of eye squeeze component of PIPP-R, mean (SD)	0.19 (0.4)	1.42 (0.8)	0.41 (0.5)	< 0.001
e) Sub-score of nasolabial furrow component of PIPP-R, mean (SD)	0.14 (0.3)	1.17 (0.7)	0.20 (0.4)	< 0.001
f) Sub-score of behavioural state component of PIPP-R, mean (SD)	1.44 (0.8)	0.74 (0.8)	1.33 (0.7)	< 0.001
Total Score PIPP-R, mean (SD)	3.60 (1.8)	8.18 (2.6)	4.24 (2.0)	< 0.001
II. Physiological parameters
HR (beats/min), mean (SD)	151.10 (19.4)	160.43 (20.4)	151.95 (21.4)	< 0.0001
SPO2 (%), mean (SD)	94.43 (5.2)	91.53 (4.7)	93.7 (4.0)	< 0.0001
RR (cycles/min), mean (SD)	61.02 (10.3)	65.68 (10.6)	62.07 (10.8)	< 0.001
PI, mean (SD)	0.85 (0.48)	0.80 (0.46)	0.85 (0.5)	0.001
Systolic BP (mm Hg), mean (SD)	74.47 (14.2)	-	75.08 (13.8)	0.244
Diastolic BP (mm Hg), mean (SD)	39.01 (9.9)	-	39.44 (9.7)	0.384
Mean arterial pressure (mm Hg), mean (SD)	52.53 (11.2)	-	53.41 (11.2)	0.031

All values are in Mean (SD).

Amongst the physiological parameters, heart rate and respiratory rate were significantly higher during the procedure. SpO₂ and perfusion index were significantly lower during the procedure compared to before and after. Though the mean blood pressure was significantly higher after Tn-Echo, the systolic and diastolic components were comparable (Table 2).

Total PIPP-R score was 1 to 2 points higher in preterm infants compared to term infants and this persisted before, during and after the procedure (Table 3).

Table 3

Comparison of physiological parameters and PIPP-R score between term and preterm neonates

Parameters		Preterm	Term	P value
Mean Gestational Age, mean (SD)		31.4 (3.4)	38.3 (1.0)
HR (beats/min), mean (SD)	Before	153.3 (19.8)	145.8 (17.5)	0.100
	During	163.8 (20.7)	152.2 (17.5)	0.014
	After	154.2 (22.2)	146.6 (18.0)	0.129
SPO2 (%), mean (SD)	Before	92.6 (8.0)	95.1 (3.3)	0.035
	During	89.9 (6.4)	92.2 (3.6)	0.039
	After	92.2 (5.3)	94.4 (3.1)	0.023
RR (cycles/min), mean (SD)	Before	60.0 (8.4)	63.3 (13.8)	0.167
	During	65.0 (8.7)	67.1 (14.3)	0.404
	After	61.1 (8.8)	64.3 (14.5)	0.213
Perfusion Index, mean (SD)	Before	0.80 (0.5)	0.97 (0.6)	0.154
	During	0.74 (0.4)	0.94 (0.6)	0.075
	After	0.81 (0.4)	0.95 (0.5)	0.197
Systolic BP (mm Hg)	Before	72.7 (15.1)	78.5 (11.0)	0.085
Mean (SD)	After	73.3 (13.9)	79.1 (11.8)	0.064
Diastolic BP (mm Hg)	Before	38.1 (10.5)	41.3 (8.0)	0.162
Mean (SD)	After	38.7 (10.1)	41.0 (8.6)	0.311
Mean Arterial BP (mm Hg)	Before	50.8 (11.5)	56.4 (9.7)	0.033
Mean (SD)	After	51.7 (11.1)	57.4 (10.6)	0.027
Total PIPP-R Score	Before	3.92 (1.8)	2.85 (1.7)	0.013
	During	8.76 (2.4)	6.81 (2.4)	0.001
	After	4.73 (2.0)	3.08 (1.7)	< 0.0001

4 Discussion

Limited data is available as to whether Tn-Echo causes significant discomfort or pain to neonates. Few tertiary care units use some form of non-pharmacologic means of analgesia but there is very little objective evidence to support that echocardiography causes pain or physiological instability. The most common physiological responses associated with acute pain are increase in heart rate and respiratory rate and decrease in SpO₂ [6, 7]. Aktas et al. has described significant pain and physiological stress in neonates undergoing Tn-Echo [8]. In our study too, we found a significant increase in the total PIPP-R score and significant change in physiological parameters like increase in heart rate and respiratory rate and decrease in SpO₂ and perfusion index during the Tn-Echo examination, indicating moderate pain/discomfort. This might be due to the pressure of the transducer over the chest and it might vary with different users performing Tn-Echo. Potana et al. in their randomized trial found similar PIPP-R score during neonatal echocardiography examination in the group without analgesia [9].

Preterm neonates have a lower threshold for nociceptive stimuli and even non nociceptive tactile stimuli can cause significant pain in these neonates [10]. Aktas et al. found significantly higher pain scores in the neonates < 32 weeks gestation compared to higher gestational ages [8]. In our study we found that the PIPP-R scores were significantly higher in the preterm neonates compared to term neonates and heart rate and SpO₂ were significantly higher and lower respectively during Tn-Echo. However, blood pressure measurements before and after the Tn ECHO were comparable between the groups.

The limitation of our study is that confounding factors like severity of sickness and respiratory support may have contributed to underscore or overscore the PIPP-R scoring in these subjects. Also, the time taken for these neonates to return to baseline scores was not studied. However, most neonates returned to baseline scores after 10 minutes of completion of the examination.

5 Conclusion

Neonates feel mild to moderate pain and are subject to physiological instability during targeted neonatal echocardiography. While interventions like swaddling may not be feasible, other non-pharmacological and pharmacological measures of pain relief during Tn-Echo need to be studied in randomized controlled trials.

Statement of ethics

This study has been approved by the “Institutional Ethics Committee Human research, Lokmanya Tilak Municipal Medical College and General Hospital”. Reference number is IEC/56/20 (dated 05.10.2020)

Human research statement

This study was conducted in accordance with the ethical standards of all applicable national and institutional committees and the World Medical Association’s Helsinki Declaration.

Conflict of interest statement

The authors do not have any conflict of interest.

Funding

None.

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