Bedside surgery to treat patent ductus arteriosus in low-birth-weight premature infants.

BACKGROUND: Patent ductus arteriosus (PDA) is commonly seen in premature infants with low birth weights (LBW). It is a condition that has high mortality and morbidity rates. Early closure of the ductus arteriosus may require surgery or medical treatment. However, the decision of first medical approach for symptomatic PDA closure is still debated. In this study, we compared the surgical and medical treatments for the closure of PDA in premature LBW infants.
METHODS: This study included 27 premature infants whose birth weights were lower than 1500 g, who were born in the period between 2011 and 2013 and had symptomatic PDA. Patients were separated into two groups: groups A and B. Group A included patients whose PDAs were closed with medical treatment (n = 16), and group B included patients who had undergone surgical operations for PDA closure (n = 11).
RESULTS: There were no statistically significant differences between groups A and B when the groups were compared in terms of birth weight, gestational age, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), sepsis, intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), and pneumothorax. Although the mortality rate was determined to be lower in group B (2 out of 11, 18.1%) than in group A (7 out of 16, 43.7%), no statistically significant difference was found between the two groups. A statistically significant increase was determined in the incidence of kidney function loss in patient group that received Ibuprofen, a medical treatment, in comparison to the patients who had surgery.
CONCLUSION: In conclusion, surgery is a safe method to repair PDA in premature LBW infants. Although there is no remarkable difference between surgery and medical treatment, we suggest that a surgical approach may be used as a first choice to repair PDA considering the lower rate of mortality and morbidity and higher rate of closure compared to medical treatment.

Introduction

Patent ductus arteriosus (PDA) is a common disease that is seen in premature low-birth-weight (LBW) infants. It affects approximately 40–55% of preterm infants born at less than 29 weeks gestation and/or weighing less than 1500 g at birth. PDA may lead to a number of complications including chronic pulmonary disease (CPD), intracranial hemorrhage, necrotizing enterocolitis (NEC), renal failure, and metabolic acidosis. Surgical approaches and medical treatment may be applied for the early closure of PDA. However, there is no consensus on the first choice of treatment.1–3 Medical agents such as intravenous (i.v.) or oral ibuprofen and i.v. indomethacin may be used to treat PDA.4 In this study, we compared the reliability and results of surgical and medical treatments for the closure of PDA in premature LBW infants.

Materials and Methods

In this study, premature infants (n = 27) diagnosed with symptomatic PDA and LBW (<1500 g) and followed in an intensive between 2011 and 2013 were retrospectively analyzed. Ethics committee approval was not required because of the retrospective nature of the study. Patients were separated into two subgroups according to the type of treatment given for PDA repair: group A included patients who only had medical treatment while patients who had only undergone surgery were included in group B. Patients were not included in this study if they had surgery after unsuccessful PDA closure with medical treatments. The parameters evaluated included gestational age, birth weight, the presence of NEC, respiratory distress syndrome (RDS), intraventricular hemorrhage, and length of hospital stay.

Patients in group A were treated with i.v. ibuprofen for three days, receiving a dosage of 10 mg/kg on the first day, and 5 mg/kg on days 2 and 3. Transthoracic echocardiography (TTE) was performed in patients at the end of the third day of treatment. Patients in group B had directly undergone surgery without taking any medicine for the PDA repair. Bedside surgery was performed for all patients in the premature intensive care unit.

A “bedside surgery” team, including cardiovascular surgeons, specialists of neonatology and anesthesiology, nurses, and other assisting personnel, has performed the bedside interventions. Main reason of bedside surgery is poor thermal regulation of prematures. All surgical interventions have been performed in the incubator. Simplification of devices and lines with complete monitorization is essential. A heater is also an important part of surgical field. Safe lines for medications were created for anesthesiologist and neonatologists. The iodine solution for skin cleaning was preheated to 37°C before surgery. Placement of the electrocautery plaque is a very important issue. Avoiding of getting wet and adequate sizing is essential. A limited standard left posterolateral thoracotomy incision under general anesthesia was chosen in all cases. PDAs were doubly ligated with ligasure clips.

Results

The total number of patients included in this study was 27, of which 16 were in group A and 11 were in group B. The gender distribution in the study groups was 14 males and 13 females. The average birth weight was 916.6 ± 225 g in group A and 915.7 ± 278 g in group B. The mean date of birth (DOB) was 189.4 ± 19 days in group A and 191.5 ± 24 days in group B. The general characteristics and preoperative conditions of the patients are listed in Table 1.

Table 1

General characteristics and preoperative conditions of the patients.

	GROUP A (n = 11)	GROUP B (n = 16)	P VALUE
Sex	Male: 7 (%63)	Male: 7 (%44)
	Female: 4 (%37)	Female: 9 (%56)
Gestasyonel age (day)	191.5 ± 24	189.4 ± 19	0,132
Birth weight (gr)	915.7 ± 278 gr	916.6 ± 225 gr	0,693
RDS	10 (90%)	11 (68.7%)	0,342
NEC	1 (9%)	2 (12.5%)	0,904
SEPSIS	10 (90%)	13 (81.2%)	0,680
IVH	3 (27.2%)	5 (31%)	0,577
ROP	10 (90.9%)	12 (75%)	0,512
Pneumothorax	1 (9%)	–	0,716

Abbreviations: RDS, respiratory distress syndrome; NEC, necrotising enterocolitis; IVH, intraventricular hemorrhage; ROP, retinopathy of prematurity.

There was no statistically significant difference between the two groups when patients were compared in terms of birth weight, gestational age, presence and severity of RDS, NEC, sepsis, intraventricular hemorrhage (IVH), retinopathy of prematurity (ROP), and pneumothorax (P > 0.05) (Table 1).

Although the death rate was lower (2/11, 18.1%) in group B than in group A (7/16, 43.7%), there was no significant difference between the two groups. In group A, three patients died from sepsis, one from NEC, one from heart failure, and two from pulmonary disorders, while in group B, one patient died from sepsis and one patient died from CPD. Hospital stay was determined to be longer in group B than in group A, but this difference was not found to be statistically significant (Table 2).

Table 2

Mortality rates and length of in-hospital stay.

	GROUP A (n = 11)	GROUPB (n = 16)	P VALUE
Death	2 (18.18%)	7 (43.75%)	0,422
Length of in-hospital stay (days)	80 ± 2.3	46,5 ± 1.2	0,349

Furthermore, in group A, the levels of creatinine were increased from 0.78 ± 0.30 to 1.23 ± 0.50 in response to medical treatment. The difference was statistically significant (P < 0.01) (Table 3).

Table 3

Creatinine levels of the study groups.

	PREOPERATIVE CREATININE LEVELS	POSTOPERATIVE CREATININE LEVELS	P VALUE
Group A	0,76 + 0,2	0,84 + 0,36	0,37
	CREATININE LEVELS BEFORE MEDICAL THERAPY	CREATININE LEVELS AFTER MEDICAL THERAPY	P VALUE
Group B	0,78 + 0,3	1,23 + 0,5	<0,01

Increases in the values of creatinine were also observed in the postoperative period of the group B (Cr: 0.84 ± 0.36) as compared to the preoperative period (Cr: 0.76 ± 0.2). However, the difference was not found to be statistically significant (Table 3).

Discussion

The ductus arteriosus is a blood vessel that connects the pulmonary artery to the aorta. PDA affects approximately 31% of infants whose birth weight is between 501 and 1500 g. Functional closure occurs in the majority of term neonates by 9–12 hours after birth.5 The incidence of PDA is inversely proportional to gestational age and infants with the lowest gestational ages are the most exposed to the complications of prematurity. The major factor closing the ductus arteriosus is the tension of oxygen, which increases significantly after birth. The patency of the ductus arteriosus has ever been considered as a pathological situation in preterm infants and one likely cause of mortality and morbidity, including bronchopulmonary dysplasia, necrotizing enterocolitis, intraventricular hemorrhage, and ROP.6

Prostaglandin E2 has the opposite effect to that of oxygen; it relaxes smooth muscle and tends to inhibit the closure of the ductus arteriosus. Non-steroidal anti-inflammatory agents, such as indomethacin or ibuprofen, have been shown to be effective in closing or preventing PDA, with differences in side effects. Indomethacin has long been the drug of choice to treat PDA. However, indomethacin inhibits the synthesis of all prostaglandins, a wide variety of adverse effects can be expected, including NEC, intestinal perforation, renal failure, thrombocytopenia, and renal disfunction. More recently, ibuprofen has been proposed for the treatment of PDA as it was shown to induce less adverse effects on cerebral blood flow, intestinal, and renal hemodynamics, while retaining similar efficacy to indomethacin.7 Ibuprofen significantly impairs renal function in preterm infants with a GA ≤ 26 weeks and/or in ELBW neonates, while it may be considered safe for infants with a BW > 1000 g and/or GA > 26 weeks.8

Factors affecting the outcomes of surgical ligations, indications, and optimal time of surgery in very low-birth-weights infant (VLBWI) are unclear. It was concluded that PDA ligation can be considered at any time in VLBWI when medical therapy either failed to close or was contraindicate.9 There is a risk of complication with the surgical repair of PDA. These complications include pneumothorax, intraoperative hemorrhage, phrenic nerve paralysis, vocal cord paralysis, and wound infection. However, of the patients in the surgical group B, only one case was observed to develop the complication of pneumothorax.

A recent study revealed that there was no significant difference between patients (n = 154) who had surgical treatment and those who had medical treatment for PDA closure with respect to the presence of hospital mortality, CPD, NEC, sepsis, IVH, and levels of creatinine. Additionally, while a low rate of failure was found in surgical closures of PDA, an increase was observed in the incidence of pneumothorax and ROP. Moreover, it was emphasized that more studies should be conducted to clarify the issue of choosing the first approach of either surgical or medical treatment in symptomatic PDA in LBW infants.1

Mosalli et al suggested that the prophylactic surgical ligation of the duct does not result in any significant differences of mortality, IVH, CPD, and ROP among the two study groups. Interestingly, the study reported a significant reduction in severe NEC, in the prophylactic surgical group, as compared to infants who received selective treatment for hemodynamically significant PDA.10

We found that there were no significant differences, among the two groups, when it came to hospital mortality and RDS, NEC, sepsis, and IVH. However, a statistically significant increase was determined in the incidence of kidney function loss in patient group that received Ibuprofen, a medical treatment, in comparison to the patients who had surgery (P < 0.05). The preoperative risk scores were high for all the patients, therefore an increased mortality in hospital and a prolonged hospital stay was observed in both patient groups.

Conclusion

Bedside surgery is a safe therapeutic approach for the closure of PDA in premature LBW infants. Although it was not statistically significant, our results demonstrated that the rate of mortality and morbidity was lower in surgically treated patients than in medically treated patients. Therefore, we suggest that a surgical approach may be used as a first choice to repair PDA considering the lower rate of mortality and morbidity and higher rate of closure compared to medical treatment.