The impact of targeted oxygen reduction test in preterm infants on reducing the oxygen exposure

Abstract

BACKGROUND:

Caring for infants on respiratory support is a challenge in the middle-income countries, applying a protocol of targeted oxygen reduction test (tORT) guided by daily assessment of oxygen histograms is novel and practical approach.

OBJECTIVE:

To study the impact of tORT guided by daily assessment of oxygen histograms as a quality improvement project aiming to decrease days on oxygen support, and duration of hospital admission in preterm infants.

STUDY DESIGN:

A quality project conducted in neonatal intensive care units (NICU) of two hospitals, from 2017- 2018 (Epochs II). After a period of observation of a cohort of preterm Infants, 2016-2017 (Epoch I). The main aims were to reduce days on oxygen and hospital admission days. All infants in Epoch II underwent daily assessment of oxygen histograms and a trial of oxygen reduction if applicable as per a predefined protocol. Comparison was made between these two Epochs, and the primary outcome was the time to successful discontinuation of oxygen support.

RESULTS:

Fifty-nine infants were included; 30 underwent the protocolized tORT (Epoch II) with a median (IQR) of 4 (2–6) tORC per infant. Postanal age at presentation (time of initial tORT assessment was performed at the postnatal age of 8 (5, 13) days. Days on oxygen and total numbers of hospital days were significantly less in Epoch II. Oxygen histograms significantly improved after tORT.

CONCLUSIONS:

Applying tORT guided by oxygen histograms may have a significant impact on oxygen exposure and hospitalization days of patients admitted to the NICU.

Keywords

Oxygen reduction test oxygen exposure preterm infants

1 Introduction

Oxygen is the most frequently used drug in premature infants [1]. Premature infants are at risk of adverse outcomes from both hyperoxia and hypoxemia [2]. Hyperoxia increases the risk of death and adverse neurologic outcomes, bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP) [3, 4]. The nurses are the key health providers responsible for adjusting oxygen in NICU, and it is a challenge to keep the oxygen requirement within the target limit if the ratio of nurses to sick infants is low, which is a common situation in middle income countries is. The health care providers tend to be more tolerant to higher oxygen saturations and less tolerant to lower oxygen saturation, adding to that the limitation of pulse oximetry in assessment of hyperoxia [5]. This is a quality project that was conducted to decrease days on oxygen for preterm infants on respiratory support which may also decrease admission days. The intervention test is by applying oxygen reduction guided by daily assessment of oxygen histograms, this will define the acceptable FiO₂ that could maintain oxygen saturation within the target saturation for longer period of time.

2 Methods

The ethical board considered the protocol as a quality improvement project so no consent was required before recruitment. We included preterm infants required oxygen with FiO₂ > 0.3 for more than 24 hours either on invasive or non-invasive ventilation using the following protocol in steps: 1) targeted neonatal echocardiography (TNE) to check hemodynamically significant patent ductus arteriosus (HSPDA) and treat with non-steroidal anti-inflammatory drug (NSAID) as per the local guidelines; 2) daily evaluation of oxygen histograms which is measurement of the cumulative time of oxygen saturations <80% (risk of hypoxemia), 81–85% (low oxygen saturation). 86–94% (the acceptable target saturation) and >95% (risk of hyperoxia) by pulse oximetry in 30 Preterm infants on oxygen support to help in continuously weaning to the lowest FiO₂ required to maintain target saturation between 86% to 94% [6]. If indicated additional routine check of optimized lung inflation and ventilation by chest x-ray (CXR) and blood gases adjustment of lung inflation according to CXR and correction of hypoventilation defined as PaCO₂ > 60 mmHg in the blood gases

2.1 Monitoring of oxygenation and intervention

Arterial oxygen saturation (SpO₂) was monitored using the Masimo Rad 7 Massimo® (Massimo Corporation, Irvine, California) pulse oximeter.

2.2 Targeted oxygen reduction test (tORT)

The test was done every 24 to 72 hours as long as the infant was still on oxygen supplementation. The tORT was not considered if oxygen histogram was >5% for SpO2 < 80% (risk of hypoxemia), and it was considered daily if the oxygen histogram >10% for SpO2 > 95% (risk of oxygen toxicity). Infants receiving supplemental oxygen of 0.3 or less were eligible for weaning trial to room air; if supplemental oxygen is more than 0.3 tORT was aiming to decrease oxygen as tolerated. Infants on volume or pressure support either mechanical ventilation or continuous positive airway pressure were kept on same pressures and ventilator sittings during the tORT. The test was described by Walsh et al. as oxygen reduction test to define bronchopulmonary dysplasia at the postmenstrual age of 36 week [7 –9]. In the oxygen reduction phase, if there was apnea (cessation of breathing for 20 seconds), or bradycardia (heart rate <80 beat/minute for more than 10 seconds), the oxygen reduction stopped.

2.3 Interpretation with tORT

Successful tORT was considered if SpO₂ was maintained after reduction phase for 60 minutes. Failed tORT was defined as oxygen saturation 80 to 85% for >5 minutes, or <80% for >1 minute, then FiO₂ was increased back to the base line. Repeated failures was considered as an early predictor of evolving bronchopulmonary dysplasia [8, 9]. If the infant with successful tORT with a new baseline FiO₂ was identified as the new acceptable FiO₂ that the bedside nurse should be aiming to lower FiO₂ back to it if the infant temporary required higher oxygen due agitation, handling, or procedures (Fig. 1).

Fig. 1

The flow diagram protocol of targeted oxygen reduction test.

2.4 Statistical analysis

Patients’ data were analyzed using SPSS 23.0 for windows 7. The infants were divided into two groups based on the presence of the outcomes of interest. Quantitative variables were expressed by mean and SD (Standard deviation), compared using Wilcoxon signed-rank test. Correlation coefficient was used for correlating quantitative variables. Qualitative variables were expressed by numbers (frequency) and percent compared between groups using Chi-square. Logistic regression analysis was performed. The optimal cut-off was determined for the variables required. P value was considered to be significant if <0.05.

3 Results

Fifty-nine infants included, 30 infants in epoch two with tORT was applied as a quality project to reduce days on oxygen and hospitalization and 29 in epoch one before implementing the protocol. Gestation age was 31.6 (30, 32) weeks, 32 (31, 33) weeks, and birth weight 1600 (1450, 1740) g, 1645(1465, 1740) g, for Epoch I and Epoch II respectively. Postnatal age at presentation (time of initial tORT assessment was performed at the postnatal age of 8 (5, 13) days. Each infant underwent 4 (IQR 2–6) tORT. Days on oxygen and total numbers of hospital days were significantly less in Epoch two. Five infants diagnosed and treated for PDA before applying tORT (Table 1). Table 2 and also Fig. 2 show the five ranges of oxygen histograms before tORT and 24 hours after the test for those who passed and FiO₂ maintained at the new defined oxygen requirement as per tORT.

Table 1
The clinical characteristics of Epoch I and II

Clinical characteristics Epoch I Epoch II P value

Number of cases 29 30 –

Birth weight (g) 1600 (1450, 1740) 1645 (1465, 1740) >0.05

Gestational age (weeks) 31.6 (30 : 33) 32 (31, 33) >0.05

Male sex (%) 60% 55% –

Confirmed systemic infection 4 cases 5 cases –

Days on mechanical ventilation 5 (I2–5) 4 (3–6) >0.05

Days on oxygen 1 (3–16) 5 (2–8) <0.05

FiO₂ 0.38 (0.31–0.43) 0.26 (0.24–0.28) <0.05

Hospital days 25 (14–37) 9 (6–12) <0.05

Chronic lung disease 2 cases One case –

Infants with treated PDA 3 cases 5 cases –

Clinical characteristics	Epoch I	Epoch II	P value
Number of cases	29	30	–
Birth weight (g)	1600 (1450, 1740)	1645 (1465, 1740)	>0.05
Gestational age (weeks)	31.6 (30 : 33)	32 (31, 33)	>0.05
Male sex (%)	60%	55%	–
Confirmed systemic infection	4 cases	5 cases	–
Days on mechanical ventilation	5 (I2–5)	4 (3–6)	>0.05
Days on oxygen	1 (3–16)	5 (2–8)	<0.05
FiO₂	0.38 (0.31–0.43)	0.26 (0.24–0.28)	<0.05
Hospital days	25 (14–37)	9 (6–12)	<0.05
Chronic lung disease	2 cases	One case	–
Infants with treated PDA	3 cases	5 cases	–

Data are presented as median± (IQR).

Table 2

Oxygen histograms before tORT and 24 hours after passing the test with maintained lower FiO₂

	Oxygen histograms Before tORT (FiO2 > 0.3)	Oxygen histograms After tORT (if passed)
SpO2 > 95	50 (44–62)	12 (8–17)	<0.05
SpO2 95–91	38 (19–45)	43 (38–49)	>0.05
SpO2 85–90	8 (5–12)	39 (33–46)	<0.05
SpO2 84–80	2 (1–3)	3 (1–5)	>0.05
SpO2 < 80%	1	3 (2–5)	>0.05

Data are presented as median± (IQR).

Fig. 2

The oxygen histograms before and after tORT.

4 Discussion

One of the main challenges in the NICU is maintaining oxygen with a physiologic acceptable target [10] and minimizing both hypoxemia and hyperoxia for preterm infants on respiratory support and at risk of hypoxemic respiratory failure [11, 12]. Oxygen therapy is one of the difficult therapies in adjustment, and the main responsibility of adjusting the level is oxygen is carried out by the bedside nurse. In the low to middle income countries the nurse to patient ratio can be >1 : 6 which usually end with delayed weaning or difficulty in determining the baseline oxygen requirement. We designed targeted oxygen reduction protocol guided by oxygen histograms as a quality program aiming to minimize both hypoxemia and hyperoxia, and identifying the most physiologic FiO₂ just enough to maintain oxygen exchange and compensate for underlying ventilation perfusion mismatch [13 –15]. The main outcome was to reduce days on oxygen and hence hospital admission days. The recruited infant all were of the middle premature age group in both Epochs and both days on oxygen and days of hospital stay were significantly lower in the Epoch II after applying rORT protocol. Daily reporting of oxygen histogram which has been used to guide tORT has been shown significant clinical benefit for daily assessment of infants on respiratory support for early detection of both worsening hypoxemia and hyperoxia [6, 16]. There was no reported cases of ROP and that could be related to most recruited infants from the middle gestational age. Our results are in agreement with a comparable study conducted by Giovanni Vento et al., where six of 23 tested babies (26%) passed the oxygen reduction test at 28 days of life, four of 10 tested babies (40%) passed at 36 weeks. Median values of SpO₂ were significantly higher in the neonates passing the test, respect to the failing patients, although our study considered the tORT on daily bases and based on daily oxygen histogram not just SpO₂ which is a novel idea and never been conducted in a similar design [10]. The impact of shorter hospital stay has significant reduction of the cost which is relatively high in middle income countries, and it has also ethical impact as early discharge would provide proper maternal baby bonding and more success of continued breast feeding.

This protocol is reproducible in neonatal units in both units with low and reasonable nursing staff to beds ratio. The main limitations of this report are small number of the assessed cases, and all recruited cases from the middle gestational age group with mild to moderate respiratory diseases, large studies including less mature infants with severe hypoxemic respiratory failure should be considered first before generalize this protocol to all neonatal population.

5 Conclusions

Applying tORT guided by oxygen histograms may have a significant impact on reducing oxygen exposure in preterm infants and total days of hospitalization of patients admitted to the NICU. More studies should be considered before applying this protocol on very premature infants.

Funding source

No Funding was secured for this study.

Disclosure

The authors have no financial relationships to disclose and no conflict of interest.

The material is original research, has not been previously published and has not been submitted for publication elsewhere while under consideration.

This project was conducted as a PhD project for fulfillment of Doctorate degree which was passed the defense and the first author was the candidate.

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