The Outcome of Operated Neonates with an Isolated Congenital Diaphragmatic Hernia in a Limited Resource Scenario: A Critical Analysis.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) is one of the most common neonatal emergencies, and the ideal current therapy requires high standards of neonatal care and advanced facilities. However, majority of neonates born with CDH are treated in public sector hospitals, with limitations in resources and workforce.
OBJECTIVES: The aim of the study was to review and analyze the outcome of operated neonates with isolated CDH in a public sector hospital and medical college where a standard protocol of management was followed, considering the need for optimization of therapy in view of the resource constraints.
MATERIALS AND METHODS: A retrospective chart review and analysis of the antenatal, preoperative, operative, and postoperative records of all neonates with operated CDH during the 3-year period from June 2015 to June 2018 at the hospital was done. The standard institutional protocol being followed included preoperative stabilization, risk stratification for patient selection, early decision regarding operative intervention, and continued postoperative ventilation.
RESULTS: During the 3-year period, 78 children were admitted with CDH, of which 40 newborns with operated CDH were studied. The mean age at surgery was 72 h. Thirty-five of these 40 cases (87.5%) made an uneventful recovery, while mortality was 5/40 (12.5%). All mortalities (5/40) occurred during the postoperative period after 3 days due to respiratory failure while being ventilated.
CONCLUSION: The strategy of a uniform protocol in the management of CDH adapted to the practical constraints of the institution yielded good results in the low-to-moderate risk group of neonatal CDH. The approach also facilitated the segregation of high-risk cases and optimal utilization of available facilities in a limited resources scenario. Copyright:

INTRODUCTION

Congenital diaphragmatic hernia (CDH) is one of the most common neonatal emergencies and the ideal current therapy requires high standards of neonatal care and advanced facilities. However, majority of CDH are treated in public sector hospitals, especially in developing countries, with limitations in resources and workforce. All possible methods should be adopted to improve results in these high-volume centers, utilizing the available resources.

Objectives

The aim of the study was to review and analyze the outcome of operated neonates with isolated CDH in a public sector hospital and medical college where a standard protocol of management was followed, considering the need for optimization of therapy in view of the resource constraints.

MATERIALS AND METHODS

A retrospective analysis of the antenatal, preoperative, operative, and postoperative records of neonates with operated CDH during the 3-year period of June 2015 to June 2018 at a public sector teaching hospital was done. A standard institutional protocol of preoperative stabilization, risk stratification for patient selection, early decision regarding operative intervention, and continued postoperative ventilation was being followed in the management of CDH during the past decade. The institutional series was reviewed, especially with regard to the outcome of operated cases of isolated CDH. The practical limitations in the treatment of CDH in a limited resources scenario were analyzed. The study involved a detailed analysis of the select group of operated cases of isolated neonatal CDH, with no major associated anomalies. Among all the cases of CDH treated during this period, the exclusion criteria were (1) nonoperated cases of CDH (where mortality occurred during medical stabilization), (2) delayed postnatal diagnosis/CDH presenting beyond the newborn period, where a uniformly good prognosis is expected, (3) CDH with multiple or major associated anomalies (cardiac anomalies (cardiac anomalies such as Tetralogy of Fallot; isolated, uncomplicated, cardiac defect such as small atrial septal defect or ventricular septal defect was not an exclusion criterion), and (4) syndromic association or genetic anomalies. This was planned as a pilot study, prior to a more extensive analysis of all cases of CDH, also involving the department of neonatology.

The salient guidelines followed in the institutional protocol for CDH are summarized here. The same consultant remained in charge of the case from prenatal consultation to postnatal care, including operative and postoperative care. The cases were managed in association with the neonatologist, who was primarily responsible with regard to medical stabilization and ventilation strategies. Endotracheal intubation and mechanical ventilation (MV) was done in all antenatally detected cases (to prevent the neonate from slipping into the vicious cycle of hypoxia, hypercarbia, and acidosis).[12] Trial of spontaneous respiration was not encouraged for the same reasons. Bag-valve-mask ventilation was strictly avoided.[345] Sildenafil was started at the earliest in the presence of clinical (requirement of high ventilator settings and FiO2) or echocardiogram evidence of pulmonary arterial hypertension (PAH). The dosage given was 1 mg/kg/dose, twice daily, administered through the enteral route, via the nasogastric tube. Sedation was used for all mechanically ventilated newborns with CDH. Deep sedation and neuromuscular blockade were provided selectively in the event of higher ventilation or oxygen requirements.[67] The aim was to achieve preductal SaO2 of 80%–95%, postductal SaO2> 70%, arterial pCO2 between 45 and 60 mm Hg, and a pH of 7.25–7.40.[78910] Oxygen supplementation was titrated to achieve a preductal saturation of 85%–95%. The preferred ventilation strategy was pressure-cycled ventilator with initial continuous mandatory ventilation, followed by intermittent mandatory ventilation, peak inspiratory pressure (PIP) <25 cm H2O, positive end-expiratory pressure (PEEP) of 3–5 cm H2O, and ventilator rate of 40–60/min.[8910]

Echocardiogram was done at 24–48 h to rule out structural cardiac defects, assess pulmonary artery size, the severity of PAH, presence and direction of ductal and intracardiac shunting, and right and left ventricular function. The severity of PAH was graded on the basis of echocardiogram findings and arterial blood gas (ABG) analysis.[8910] PAH was defined as a mean pulmonary artery pressure ≥25 mmHg on echocardiogram.[1112] Absence of evidence of PAH on echocardiogram along with a requirement of low ventilator settings (PIP <20 cm H2O, PEEP <3 cm H2O and FiO2<0.5) to maintain saturation was defined as absent PAH, while those with evidence of PAH and requiring increased ventilator support (PIP >20 cm H2O, PEEP >3 cm H2O and FiO2 >0.5) to maintain vital parameters were classified as mild-to-moderate PAH. Those neonates who had evidence of PAH with right ventricular abnormalities and inability to maintain saturation even with increased ventilator settings were classified as severe PAH.

The essential tenets of CDH management including gentle ventilation, spontaneous respiration (whenever possible), “permissive hypercapnia,” minimization of stimuli that worsen PAH, and prevention of ventilation-associated lung injury were adhered to in all cases. Surgery was considered after initial stabilization, based on the indices of ventilator support and results of ABG analysis. A clinically stable neonate without major anomalies and no significant abnormality on echocardiogram at 24 h was taken up for relatively early surgery at 24–48 h [Refer Figure 1]. This decision was based on the fact that a child who is relatively stable on ventilator is unlikely to have very severe pulmonary hypoplasia and hence better chance of survival. The surgery was not delayed beyond 72–96 h unless there was an overwhelming contraindication like the presence of a major associated anomaly, requirement of high ventilation parameters, or adverse ABG analysis. Due to the unavailability of extracorporeal membrane oxygenation (ECMO), the treatment strategy in children who were unstable even on maximal ventilator support was individualized. Prolonged preoperative ventilation (beyond 72–96 h) was not a viable option in many situations due to the constraint in the number of ventilators, which were also required for other newborns with medical problems. The decision to proceed with surgery was taken relatively early if the child did not have features of severe PAH or major associated anomalies. However, if the neonate continued to be unstable even on maximal ventilator support, the surgery was deferred, and medical management continued. Such patients who did not undergo surgery were not included in the analysis. At surgery, anatomical closure was done in all cases, and the use of prosthetic patch for repair was not preferred. A sac, if associated, was excised and not utilized for repair. The creation of ventral hernia was considered if tight abdominal wall closure was deemed to increase the risk of abdominal compartment syndrome. A minimal water-seal pressure intercostal drain was used in all cases. A contralateral intercostal chest tube insertion was done in the event of pneumothorax due to barotrauma. Echocardiogram and serial ABG were done to monitor for the postoperative resolution of PAH. Sildenafil was continued whenever it had been given preoperatively. Gradual reduction of ventilator settings and slow, progressive weaning was practised.

Figure 1

The institutional protocol followed in management of prenatally detected congenital diaphragmatic hernia described in an algorithm

RESULTS

In this study, only select cases of operated CDH with no major associated anomalies were included for analysis, with the aim of identifying the survival pattern in isolated neonatal CDH. During the 3-year period, 78 cases were admitted with CDH, of which 40 operated cases were included in the study. The reasons for the exclusion of 38 cases from the study were (a) death during medical stabilization: 23; (b) major associated anomaly/multiple anomalies/syndromic disorders/genetic anomalies: 10; and (c) delayed postnatal diagnosis (gastric volvulus/other): 5. Twenty-five of forty (62.5%) were male and 15/40 (37.5%) were female. Twenty-one of forty (52.5%) cases underwent immediate intubation and treatment as per the standard protocol. Fifteen of forty cases (37.5%) were referred from other centers and 4/40 cases (10%) were detected postnatally at the same hospital. Thirty-four of forty cases (85%) were detected on antenatal USS, while 6/40 cases (15%) were detected postnatally. Thirty-eight of forty (95%) had left-sided CDH (classical Bochdalek hernia), while 2/40 cases were right-sided CDH (both right-sided CDHs were missed on prenatal USS). Twenty-eight of forty cases (70%) with evidence of PAH received preoperative sildenafil. Preoperative and postoperative inotrope support was required in 7/40 (17.5%) patients, which also incidentally included all the mortalities. Deep sedation and neuromuscular blockade were required preoperatively in only in one case. The minimum ventilator parameters required to maintain oxygenation and avoid barotraumas in operated CDH was graded as low/moderate/high based on mode, pressures, and volume and FiO2 required to maintain oxygen saturation. The requirement was low in 25/40 (62.5%), moderate in 7/40 (17.5%), and high in 8/40 (20%) cases. The mean duration of preoperative stabilization was 3 days. The mean age at surgery was postnatal day 3. Four of forty (10%) patients with no adverse clinical features and minimal ventilation requirements underwent relatively early surgery before 48 h of life. They required postoperative ventilation for 48–96 h, but there was no significant morbidity or mortality in this group that underwent early surgery. Thirty-two of forty (80%) were CDH without sac, while 8/40 (20%) had a sac. The stomach was intrathoracic in 7/38 cases (18%) of left-sided hernia. The left lobe of the liver had herniated in 12/38 (32%) cases of left-sided hernia. The mean duration of surgery was 75 min. The average blood loss was 10 ml. Three of forty cases (0.075%), with an inability to close the abdomen without undue tension, resulted in creation of a ventral hernia. The duration of requirement of postoperative ventilation was for 24–48 h in 12/40 patients (30%), 48–72 h in 18/40 patients (45%), and more than 72 h in 10/40 patients (25%). Thirty-five of forty patients (87.5%) recovered after surgery and were discharged and reported for the first follow-up after 2 weeks. Mortality occurred in 5/40 patients (12.5%) during the postoperative period after 3–12 days of surgery. The survival was assessed based on the data regarding the discharge of the child from the hospital. Few of the cardinal results are summarized in Tables 1-4.

Table 1

Presence of associated anomalies in operated congenital diaphragmatic hernia

Associated anomalies	n (%)
Nonmajor cardiac (ASD/VSD)	8 (20)
Renal	4 (10)
Nonmajor neurological	2 (5)

The cases of CDH with multiple/major anomalies were excluded from the study. CDH: Congenital diaphragmatic hernia, ASD: Atrial septal defect, VSD: Ventricular septal defect

Table 4

Complications during postoperative mechanical ventilation and early postoperative period, in all postoperative cases, including those who did not survive (n=40)

Complications in postoperative cases	n (%)
Severe PAH and persistent fetal circulation	4 (10)
Metabolic acidosis	4 (10)
Barotrauma (contralateral)	3 (7.5)
Abdominal compartment syndrome	2 (5)
Chylothorax	1 (2.5)
Prolonged oxygen dependency	1 (2.5)

PAH: Pulmonary arterial hypertension

DISCUSSION

This study focuses on a select group of neonates with operated CDH, with no major associated anomalies. The high incidence of postnatal detection of CDH in the era of ubiquitous ultrasound screening was surprising and was observed to be due to patients being from remote locations, antenatal follow-up and delivery at other hospitals, poor awareness of parents, and the suboptimal nature of prenatal scan, sometimes performed by the obstetrician. These patients were operated relatively early (within 4–5 days of life), once deemed to be stable during MV. Neonates who underwent prolonged MV and attempt at medical stabilization (possibly having the most severe PAH and lung hypoplasia) had very high mortality. The neonates with other major anomalies require a tailored approach and survival figures are influenced by other factors. Neonates were common taken up for surgery after 48–72 h of stabilization. Thirty-two of forty patients underwent surgery between 48 and 96 h of life. The decision to proceed with early surgery in these patients is an obvious reflection of the fact that they were relatively stable on a ventilator and were deemed to have a good chance to survive after surgery.

Although they were not included in the analysis, 23/78 patients died during continued medical stabilization and ventilation, and this is the group with the most complex disease. The decision to continue on medical therapy after 4–5 days indicates that this group of patients had the most severe disease and hence the high mortality. Thirty-four of forty patients had evidence of mild-to-moderate PAH, with severe PAH in 6/40 cases. It is notable that all the mortality among the operated group (5/40) occurred in the same group. The high survival 35/40 (87.5%) seen in this study among operated cases is a reflection of stringent patient selection and exclusion of the children with major anomalies. However, it is also indicative that survival can be maximized in isolated CDH by following a standard protocol. The survival in CDH has improved from the past figures of 40% to 50% to the presently quoted data of over 70%, with current standards of care including ECMO.[111213] However, mortality and morbidity are maximum in the group of patients with pulmonary hypoplasia and severe PAH, even with the highest level of care. A precise comparison of the survival in the present series with historical controls or previous institutional series has not been attempted in this study, as the analysis done here is focused only on a select group of patients with relatively better risk. In the absence of ECMO, the management of neonates who are unstable in spite of maximal ventilator support poses a difficult challenge, and the treatment is ideally individualized in these situations.

In an antenatally detected CDH, the option of proceeding with treatment at a center with all facilities for treatment of CDH can be given to the parents. However, such centers with affordable care are scarce, especially in developing nations. Such a decision also involves conduct of the delivery at the same specialized center, which adds further to the logistical and financial constraints. Hence, many of the children with CDH continue to be treated at these centers with practical limitations. The recommended standards in monitoring and advanced therapy are difficult to follow in these instances. Facilities such as ECMO, advanced neonatal ventilation modalities, inhaled Nitric Oxide therapy, and advanced monitoring methods are usually unavailable at these centers. This is further compounded by logistical limitations such as lack of sufficient ventilators, absence of advanced neonatal transport facilities, inability to provide dedicated nursing care, and even the lack of trained neonatologist at some centers. Strategies that involve prolonged preoperative stabilization on a ventilator are generally not feasible in this situation due to the constraint in the number of neonatal ventilators which are also required for children with medical illnesses.

The survival of newborns with CDH and esophageal atresia constitute benchmarks in the standard of neonatal surgical care. It has been well established that a standard management protocol improves the prognosis of children with CDH.[91013] Although practical limitations with regard to the availability of advances neonatal ventilators, ECMO, and sophisticated monitoring may persist in high-volume public sector hospitals, the survival in CDH can be maximized and optimal utilization of resources ensured by the establishment of a standard protocol of therapy, ensuring the conduct of delivery at the same center, proper collaboration between pediatric surgeon and neonatologist, immediate intubation and MV, aggressive treatment of PAH, identification of high-risk patients, ensuring availability of neonatal transport facilities, and selecting the optimum time for surgery. The long-term goal should be development of dedicated centers with the aim of prenatal follow-up, delivery, and management at the same center. Establishment of insurance cover for antenatally detected fetal anomalies would be a major hurdle in this regard.

CONCLUSION

The strategy of a uniform protocol in the management of CDH adapted to the practical constraints of the institution yielded good results in the low-to-moderate risk group of neonatal CDH. The approach also facilitated the segregation of high-risk cases and optimal utilization of available facilities in a limited resources scenario.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Table 2

Severity of pulmonary arterial hypertension in operated congenital diaphragmatic hernia, graded on the basis of echocardiogram findings and arterial blood gas analysis (n=40)

Severity of PAH	n (%)
None	12 (30)
Mild	16 (40)
Moderate	6 (15)
Severe	6 (15)

PAH: Pulmonary arterial hypertension

Table 3

Duration after birth when the neonate was take up for surgery

Timing of repair (after birth) (h)	n (%)
24-48	4 (10)
48-72	20 (50)
72-96	12 (30)
After 96	4 (10)

It can be noted that the majority of patients underwent surgery on 3rd day and 4th day of life