Comparative evaluation of high-flow nasal cannula oxygenation vs nasal intermittent ventilation in postoperative paediatric patients operated for acyanotic congenital cardiac defects

Abstract

Background

This study aimed to compare high-flow nasal cannula (HFNC) oxygenation vs nasal intermittent ventilation (NIV) oxygenation for respiratory care after extubation in postoperative paediatric cardiac patients.

Methods

This study was a randomised controlled trial. One hundred twenty-one paediatric patients with acyanotic congenital heart disease undergoing corrective cardiac surgery on cardiopulmonary bypass were included in the study. Patients were randomised to receive either HFNC (AIRVO) or NIV (RAM Cannula) postextubation. Arterial blood gas was analysed at different time points perioperatively.

Results

Patients in both the groups were matched with respect to diagnosis and demographic profiles. Baseline hemodynamic and respiratory parameters were also similar in both the groups. Patients in HFNC/AIRVO group did not show improved carbon dioxide (CO₂) washout but showed improved pO₂ and pO₂/FiO₂ ratio immediate postextubation. Reintubation rate and other intensive care unit (ICU) complications were similar in both the groups.

Conclusion

Postcardiopulmonary bypass respiratory complications in paediatric patients with congenital acyanotic heart disease can be minimised with newer oxygen therapy devices such as AIRVO (HFNC) or RAM cannula (NIV). In comparison between these two, AIRVO did not show improved CO₂ washout over RAM cannula; however, it did provide better oxygenation as measured by pO₂ in arterial blood and pO₂/FiO₂ ratio immediate postextubation. Also, long-term results such as duration of mechanical ventilation and ICU stay were not affected by the choice of device.

Introduction

The children with acyanotic congenital heart diseases who need surgical repair usually have an uncomplicated postoperative period. In certain cases, postoperative pulmonary complications can lead to prolonged mechanical ventilation, prolonged length of stay in the paediatric cardiac intensive care unit (PCICU) and increased mortality.¹ Pulmonary complications due to fluid accumulation, skeletal muscular weakness, and diaphragmatic fatigue have been observed in paediatric patients after cardiac surgery.² In addition, derecruitment of lung begins immediately in the absence of positive airway pressure after extubation.³ Therefore, in the postextubation period, the use of noninvasive ventilation to provide continuous positive airway pressure (CPAP) via nasal cannula has become popular.

The common modes of noninvasive-assisted ventilation are nasal intermittent ventilation (NIV) and high-flow nasal cannula (HFNC).⁴ NIV via nasal cannula delivers heated and humidified oxygen when connected to NIV mode on a conventional mechanical ventilator with adjustable positive end-expiratory pressure (PEEP), inspiratory airway pressure (Pinsp) and fractional inspired oxygen concentration (FiO₂). NIV mode delivers the desired airway pressure and compensates for the expected leaks as well as continuous distending pressure to the lung. The flow rates being delivered to the patients varies to establish and maintain the set pressures. Thus, it increases functional residual capacity (FRC), arterial oxygenation and carbon dioxide (CO₂) elimination.^5,6 Prophylactic application of nasal NIV thus can reduce the incidence of endotracheal re-intubation and pulmonary complication.^7,8

HFNC has emerged as an alternative to conventional oxygen delivery systems in neonates, infants and paediatrics age group.⁹ HFNC delivers oxygen at the desired flow rate and FiO₂ through a humidified circuit. The airway pressure is variable and cannot be controlled. It gives positive expiratory pressure, which helps in alveolar recruitment, greater wash out of dead space favouring the elimination of CO₂ and better oxygenation. It has been shown to be better tolerated by the patients.^10,11 There is paucity of literature to compare the two modes of postoperative oxygenation, HFNC and NIV in the paediatric patients after surgeries for congenital cardiac defects, although this comparison in adults does exist.¹¹ Therefore, we conducted this prospective study to compare two established modes of noninvasive ventilation in this specific population.

The primary objective of our study was to determine whether application of HFNC in postextubation period improves CO₂ elimination as measured by arterial partial pressure of CO₂ (pCO₂) compared with NIV. The secondary objectives were to evaluate the levels of arterial partial pressure of oxygen (pO₂) and the pO₂/FiO₂ ratio, reduction in the need of reintubation, length of intensive care unit (ICU) stay and other adverse events in paediatric cardiac surgical patients with HFNC compared with NIV.

Materials and methods

The study is an institutional ethical committee approved, randomised controlled trial conducted between May 2018 and December 2019 at a tertiary care paediatric cardiac care hospital in India. The study sample was enrolled from the patients admitted to the paediatric cardiology unit for cardiac surgery. The inclusion criterion was children aged <4 years undergoing elective cardiac surgery for acyanotic congenital cardiac defects under cardiopulmonary bypass (CPB). Children with major noncardiac congenital malformations and major neuromuscular disease and those with the presence of postoperative, nondrained pneumothorax or pleural effusion were excluded. The study population was randomly divided into two groups. Group HFNC consisted of patients managed with HFNC device (AIRVO2 device with Optiflow Junior nasal prong, Fisher & Paykel Healthcare Limited, Auckland, New Zealand), and Group NIV consisted of patients managed using NIV delivered by mechanical ventilator (GE Engstrom Carestation, GE Healthcare, Finland) with Neotech RAM nasal cannula. Randomisation was simple randomisation, and allocation concealment was done using opaque envelopes. The envelope was chosen by an independent observer before the start of the surgery.

Anaesthetic technique was as per standard institutional protocol, which follows fast-tracking, that is, balanced general anaesthesia technique with epidural analgesia. All patients were taken into the operating room premedicated with intranasal ketamine 7 mg/kg and midazolam 0.5 mg/kg. Induction was done with 2 mg/kg IV ketamine supplemented with 2 μg/kg IV fentanyl, and IV Rocuronium 1 mg/kg was administered to assist oral endotracheal intubation in both the groups. After intubation epidural catheter was inserted in T4 to T8 space in lateral position. The epidural solution used was 1 ml/kg bolus of 0.25% bupivacaine, and 50 μg/kg morphine administered in two divided doses 30 min apart, followed by 0.1% bupivacaine at the rate of 0.1 ml/kg/hour, throughout the intraoperative and postoperative period in the ICU. Ventilation was maintained with 50% FiO₂ (air and oxygen mixture) and sevoflurane (1–2 MAC). Dexmedetomidine 0.25 μg/kg/hour was started intraoperatively and continued throughout the postoperative period. CPB with ultrafiltration was performed according to our standard operating procedures (see Supplementary material). After surgery, the patients were assessed for fitness to extubate with the following criteria: hemodynamic stability with minimal inotropic support, no ongoing bleeding, adequately rewarmed, and adequate reversal with standard doses of neostigmine (0.06–0.07 mg/kg) and glycopyrrolate (0.02 mg/kg). ICU sedation consisted of Inj propofol at 25 μg/kg/min for all patients till 12 h postextubation.

HFNC or NIV was applied to the patient after extubation as per the randomisation. HFNC device used in our study was capable of delivering flow rates of up to 25 L/min. The manufacturer offers disposable wide-bore snug-fitting nasal cannula of different sizes for children of various ages (Optiflow Junior Cannula). The flow rate was set at 2 L/kg. In the NIV group, a next-generation nasal cannula (RAM cannula, Neotech, Valencia, CA) was used as an interface to provide NIV.¹² RAM Cannula (Neotech) is a soft, gently curved prong designed for patient comfort, is available in seven colour-coded sizes for different nasal sizes. An airway inspiratory pressure (Pinsp) of 12 cm H₂O and PEEP of 6 cm H₂O was used in NIV group. FiO₂ in both the groups was kept at 60% for the first day and 50% for the second day to achieve target saturation >94%.

Patients on HFNC or NIV who developed cardiorespiratory instability were managed by intubation and mechanical ventilation as decided by the treating intensivist/anaesthesiologist. Arterial blood gas analysis (ABG) was done at induction, postsurgery (intubated child on ventilator after chest closure), and postextubation at 2, 12 and 24 h, respectively. The occurrence of complication because of nasal cannula was noted PCICU. Daily chest radiograph as per institutional protocol was undertaken to assess for atelectasis/pneumothorax. The demographic data of the patient were noted. Additional data noted were aortic cross-clamp time (AXC), CPB time, duration of mechanical ventilation in PCICU, length of PCICU stay in days and any adverse events in PCICU. Respiratory parameters were assessed by serial ABG as per PCICU protocol and pulse oximetry. Adverse respiratory events such as hemodynamic instability, desaturation (SpO₂ <92%) and respiratory obstruction requiring an adjustment in airway or changes in oxygen therapy in each group were recorded.

Statistical analysis

The distribution of continuous data was analysed with Kolmogorov–Smirnov one-sample test. The continuous variables with a normal distribution are expressed as mean ± standard deviation (SD), and dichotomous data are expressed as numbers and percentages. Based on the distribution of the data for continuous variable, Mann-Whitney or t-test has been used for comparing two groups. Nonparametric(k) test was used for comparing skewed data. Chi-square test is used for the categorical variables. Mixed factor repeated measures analysis of variance (ANOVA) with Tukey correction was used to find any significant difference in the respiratory rate, arterial pO₂, pCO₂, and pO₂/FiO₂ ratio between the HFNC or NIV groups. The study was powered on the primary outcome based on institutional retrospective data: considering a mean ± SD pCO₂ level, 1 h after extubation, of 45 ± 8.4 mm Hg and a 10% (4.5 mm Hg) pCO₂ difference between the two groups, to achieve a 90% statistical power with an alpha error of 0.01, the number of patients was calculated to be 52 for each group. With a 10% attrition rate, we decided to enrol a minimum 58 patients in each group. Statistical analysis was performed using SPSS software (IBM SPSS Statistics 21, Chicago, IL). A P value <0.01 was considered statistically significant.

Results

The study was conducted over 18 months. A total of 129 patients were eligible for enrolment; parents of two patients did not consent. Finally, 127 patients were included. Among the 127 patients included, 63 were randomly assigned to the NIV group and 64 were randomly assigned to the HFNC group based on the blind envelop technique. Among these, 61 and 60 patients completed study in NIV and HFNC groups, respectively (Fig. 1). The distribution of cases based on diagnosis is represented in Fig. 2. The commonest congenital heart disease was (60%) ventricular septal defect.

Fig. 1.

Consort diagram.

Fig. 2.

Diagnosis of patients in both the groups. VSD, ventricular septal defect; ASD, atrial septal defect; PS, pulmonary stenosis.

The age, height, weight, gender distribution, body surface area, CPB and AXC time, blood transfusion requirement, chest tube drainage in the first 24 h and ABG values taken preoperatively after the induction of the patients were comparable in both groups (P > 0.01; Table 1). The number of patients that were extubated in operating room was 11 in HFNC group and 13 in NIV group (total of 24). The difference between both the groups with respect to the airway manipulation, use of airway adjuncts, need to increase oxygen flow rate, desaturation event, hypotension, bradycardia, mechanical ventilation duration, length of ICU stay, the incidence of reintubation, duration of oxygen requirement postextubation, and mortality rate were not statistically significant in NIV and HFNC groups demonstrated by chi-square test/Fisher's exact test (P > 0.01; Table 1, Table 2).

Table 1.

Patient demographic characteristics, laboratory investigations, haemodynamic variables and outcome.

S No	Parameters	HFNC (n = 61)		NIV (n = 60)		T value	P value
		Mean	±SD	Mean	±SD
1	Age (months)	46.8	36.3	43.2	32.3	2.17	0.03
2	Sex (male) (a chi-square value)	32 (53.3%)		34 (56.7%)		0.13a	0.71
3	Height (cm)a	97.7	27.8	87.2	16.1	2.53	0.013
4	Weight (kg)a	14.1	7.4	12.4	5.6	1.42	0.16
5	BSA (sq m)a	0.59	0.3	0.53	0.2	1.46	0.15
6	CPB (min)	74.3	47.2	70.9	37.5	0.44	0.66
7	AXC (min)	35.2	28.1	41.3	26.8	−1.22	0.23
Preoperative arterial blood gas analysis
8	pH	7.40	0.04	7.41	0.04	−1.14	0.26
9	pO2 (mm Hg)	143.0	15.4	138.9	9.9	1.73	0.09
10	pCO2 mm Hg)	39.1	3.9	37.8	4.6	1.67	0.097
11	pO2/FiO2	365.9	75.1	347.7	48.7	1.58	0.12
Preoperative parameters
12	Respiratory rate (per minute)	23.4	3.5	23.0	6.2	0.43	0.67
13	Heart rate (bpm)	114.3	16.6	115.1	16.5	−0.27	0.79
14	Mean blood pressure (mm Hg)	67.8	5.2	71.1	8.8	−2.50	0.014
15	Pulse oximetry (spO2%)	96.1	6.1	97.6	3.3	−1.68	0.097
Outcome
16	MV duration (hrs)a	2.5	0–4.5	2.75	0–18	0.04
17	ICU stay (days)	2.8	0.75	2.9	0.95	−0.64	0.53
18	Duration of oxygen therapy post extubation (days)	1.7	0.76	1.85	0.92	−0.76	0.49
Postoperative transfusions (ml/kg)
19	PRBCa	0	0–6	3.57	0–9.1	0.36
20	FFP	13.47	6.75	14.73	8.89	−0.88	0.38
21	PC	2.58	4.12	1.06	2.39	2.48	0.015
22	Chest drain (ml/kg) after 24 h	8.93	3.80	11.62	9.23	−2.08	0.04

BSA, body surface area; CPB, cardiopulmonary bypass; AXC, aortic cross-clamp time; pO₂, partial pressure of oxygen; pCO₂, partial pressure of carbon dioxide; FiO₂, fractional inhaled oxygen concentration; MV, mechanical ventilation; ICU, intensive care unit; PRBC, packed red blood cells; FFP, fresh frozen plasma; PC, platelet concentrate.

^aMedian with interquartile range; P < 0.01 is considered significant.

Table 2.

Complication rates.

S No	Complications, n (%)	HFNC (n = 61)	NIV (n = 60)	TOTAL (n = 121)	Chi-square value	P value
1	Airway manipulation/use of airway adjuncts	4 (6.6%)	6 (10%)	10 (8.3%)	0.47	0.49
2	Need to increase oxygen flow rate	3 (4.9%)	2 (3.3%)	5 (4.1%)	0.19	0.66
3	Desaturation event	1 (1.6%)	1 (1.7%)	2 (1.65%)	0.0001	0.99
4	Hypotension	15 (24.6%)	17 (28.3%)	32 (26.4%)	0.22	0.64
5	Bradycardia	1 (1.6%)	–	1 (0.8%)	0.99	0.32
6	Abdominal distension	4 (6.6%)	7 (11.7%)	11 (9.1%)	0.90	0.34
7	Reintubation rate	1 (1.6%)	2 (3.3%)	3 (2.5%)	0.34	0.56

The results of the mixed ANOVA showed no difference in pCO₂ levels, with patients showing equivalent pCO₂ 24 h postextubation (38.9 ± 0.5) when compared with preoperative pCO₂ levels (38.6 ± 0.4; F(2.3, 264) = 2.65, P = 0.06, ηp² = 0.06). There is also no significant relationship between the use of HFNC and pCO₂ levels (F(1, 114) = 0.23, P = 0.63, ηp² = 0.002), with participants showing similar mean pCO₂ for HFNC (39.9 ± 0.45) and NIV (40.2 ± 0.4) use. At different time intervals in the postextubation period, the difference in mean pCO₂ levels between NIV group and HFNC group was not statistically significant; at 2 h (42.5 ± 7.1 vs 41 ± 8.1), 12 h (40.5 ± 6.6 vs 39.2 ± 8.5) and 24 h (38.2 ± 2.8 vs 39 ± 5.5; Fig. 3).

Fig. 3.

Box plot diagram descriptive statistics of partial pressure of carbon dioxide in blood (pCO₂) of the two groups at different periods (0, preoperative; 1, postoperative; 2, 2 h after extubation; 3, 12 h after extubation; and 4, 24 h after extubation).

The respiratory rate varied significantly with time (F(2.6, 297.8) = 13.78, P < 0.001, ηp² = 0.11) with postextubation patients showing a higher respiratory rate at 12 and 24 h when compared with preoperative rates. Descriptive statistics demonstrated that NIV use performed better for improved respiratory rate compared with HFNC use in postextubation period at 12 h (22.1 ± 4.6 vs 25.1 ± 6.6) and 24 h (23.2 ± 4.0 vs 25.8 ± 6.7) {F(2.6, 297.8) = 22.35, P < 0.001, ηp² = 0.16} (Fig. 4).

Fig. 4.

Box plot diagram descriptive statistics of respiratory rate (RR) of two groups at different time periods (0, preoperative; 1, postoperative; 2, 2 h after extubation; 3, 12 h after extubation; and 4, 24 h after extubation).

The mean pO₂ is significantly higher postextubation than preoperative pO₂ levels (F(2.4, 271.6) = 45.5, P < 0.001, ηp² = 0.29) in both the groups (Fig. 5). Moreover, there is significant effect of the use of HFNC on pO₂ (F(1, 114) = 9.16, P = 0.003, ηp² = 0.07), with participants showing higher average pO₂ for HFNC group (mean = 188.6) than NIV group (mean = 172.6). HFNC use performed better for pO₂ compared with NIV in postextubation period at 2 h (227.8 ± 6.2 vs 185.8 ± 6), 12 h (209.8 ± 7.3 vs 177.2 ± 7.1) and 24 h (191.4 ± 4.7 vs 144.3 ± 4.5; F(2.4, 271.6) = 23.89, P < 0.001, ηp² = 0.17).

Fig. 5.

Box plot diagram descriptive statistics of partial pressure of oxygen in blood (pO₂) of the two groups at different periods (0, preoperative; 1, postoperative; 2, 2 h after extubation; 3, 12 h after extubation; and 4, 24 h after extubation).

On analysing the pO₂/FiO₂ ratios, participants show higher average pO₂/FiO₂ ratio for HFNC use (395.6 ± 7.6) than NIV use (354.4 ± 7.4) (F(1, 114) = 15.1, P < 0.001, ηp² = 0.12). In addition, HFNC use performed better for pO₂/FiO₂ ratio compared with NIV use in postextubation period at 2 h (405.5 ± 87.4 vs 353.9 ± 51.7), 12 h (440.2 ± 82.3 vs 341.2 ± 129.1) and 24 h (455.3 ± 112.6 vs 309.2 ± 69.1; F(2.1, 234.8) = 33.6, P < 0.001, ηp² = 0.23; Fig. 6).

Fig. 6.

Box plot diagram descriptive statistics of pO₂ and FiO₂ ratio (pO₂/FiO₂) of the two groups at different periods (0, preoperative; 1, postoperative; 2, 2h after extubation; 3, 12 h after extubation; and 4–24 h after extubation). pO₂, partial pressure of oxygen in blood; FiO₂, fractional inhaled oxygen concentration.

Discussion

The postoperative period in paediatric patients undergoing cardiac surgery under CPB is at risk of pulmonary complications. This may be because of atelectasis and pneumonia. The contributing factors are reduced chest wall compliance, mucus plug, small airways, poor cough, lack of incentive spirometry, low birth weight, plastic bronchitis, pulmonary hypertension, genetic abnormalities and immunosuppression. The presence of surgical trauma such as vocal cord palsy, diaphragmatic palsy, and chylothorax compounds the pulmonary complications.¹³

Noninvasive ventilation helps in early extubation in such patients by its favourable effect on cardiac and respiratory physiology.^5,6 We found either methods of noninvasive ventilation to be an effective method in maintaining airway gas exchange in paediatric postcardiac surgery patients with minimal adverse effects.

Our primary outcome was to compare postoperative mean pCO₂ levels in both the groups. It has been described that the increased flow of HFNC reduces the work of breathing by flushing the nasopharyngeal space and improving CO₂ elimination.¹⁴ Testa G et al. in a randomised controlled trial in children aged <18 months undergoing cardiac surgery noted no difference in pCO₂ levels between the HFNC and free-flow oxygen therapy group.¹⁵ We found that both HFNC and NIV therapy were equally effective in preventing an increase in postextubation levels of pCO₂ in these children. When compared with NIV our study showed a beneficial effect of HFNC in improving pO₂ levels in these patients. Our study also demonstrates the efficacy of HFNC in improving the pO₂ levels postoperatively.

Interestingly, we observed 11 patients (9.1%) with abdominal distention that required adjustment of therapy. In the HFNC group, we reduced the airflow, whereas in the NIV group, we reduced the Pinsp for the management of the patients. However, there were no adverse events nor complications in either group in our study, thereby establishing the safety of the use of either HFNC or NIV. In our patients, we did not find any discomfort in either group regarding the ease of application and the ability to care for the infant, including feeding while continuing oxygen administration.

HFNC provides some level of CPAP, which depends on factors such as the infant's weight, the flow rate and the leak around the nasal cannula.¹¹ HFNC in patients who have undergone cardiac surgeries during their postoperative period has shown to decrease respiratory rate, improve end-expiratory lung volume, and reduce CPAP requirement and re-intubation rates but did not improve other parameters, such as SpO₂:FIO₂ ratios or basal atelectasis.^5,6,16,17 We did not find any difference in desaturation, intervention such as airway manipulation, use of airway adjuncts, and need to increase oxygen flow rate while comparing HFNC with NIV group. In the adult age group, both the devices have been shown to have similar reintubation rate.^18,19 Unlike Shioji et al., we did not find any difference in the reintubation rate or ICU stay among both the groups in our study.²⁰ Adverse events such as transient apnoea, hypotension, and bradycardia were also found similar in HFNC and NIV group in our study. Also, the duration of NIV support was equivalent to HFNC, and this has likely translated into a similar ICU stay. We could not justify the use of one over another for postextubation oxygen therapy, and HFNC provides respiratory support comparable to NIV. This is in agreement to the available literature.21, 22, 23, 24

We were able to assign and administer intervention in a precise, controlled way and establish the relation between the oxygen therapy and outcome in a scientific manner. The difficulty in the blinding of the treatment arm was the major cause of bias in our study. However, we could decrease selection bias and minimises confounding because of randomisation and concealment. Spirometry analysis before and after the procedure was not included as a measurement in our study. However, it could be a vital tool to provide exact differences and measurements in tidal volume and FRC levels between various oxygen delivery devices. The period of observation was relatively short and limited to 48 h; however, the fast track protocol being practised in our centre precluded us from extending this period. This study was conducted in a single centre; a large multicentric randomised controlled study will be required to compare these new methods with present practices. In addition, acyanotic defects have been chosen in this study to remove any confounding bias, which may occur because of the incorporation of children with cyanotic heart diseases, which are usually more complex.

Conclusion

HFNC is a newer method of optimising oxygen delivery to patients post extubation after paediatric cardiac surgery. Children in post CPB period develop respiratory complications, which can be minimised with newer oxygen therapy devices such as HFNC or NIV via RAM cannula. In comparison of these two methods, there is no difference in CO₂ clearance; however, HFNC does provide better oxygenation as measured by pO₂ in ABG and pO₂/FiO₂ ratio in the immediate postextubation period. The immediate postsurgical duration of mechanical ventilation and PCICU length of stay are not different. Further research is recommended to investigate the use of these devices at different flow rates in different cohorts to establish management guidelines for escalation and de-escalation of oxygen therapy.

DIsclosure of competing interest

The authors have none to declare.

Appendix ASupplementary data

The following is the Supplementary data to this article: