Case reports

Gianfranco Perotti

Neonatal Diseases and Intensive Care Unit, IRCCS San Matteo Polyclinic, Pavia

INTRODUCTION

Pulmonary hemorrhage in VLBW (very low birth weight) neonates is frequently a catastrophic and preterminal event. It generally strikes preterm neonates affected by RDS who have received substitution therapy with surfactant with an incidence of 2 to 6%, generating with a mortality rate of approx 33%.

We shall describe the clinical case of a neonate with a gestational age of 26 weeks, inborn, delivered by urgent Cesarean section due to absence of the umbilical flows following a pregnancy complicated by oligohydramnios and intrauterine growth delay. Weight at birth: 630 gr; Apgar 1’= 4 ;5’= 5 ;10’= 7.a

CASE STUDY

The neonate was intubated and administered the first dose of surfactant (Curosurf) one hour after birth, due to an increased O2 requirement (FIO2>0.4 to maintain arterial saturation >90%). The chest X-ray performed after intubation and surfactant administration is shown in (figure 1A).

The neonate was then placed under Synchronized Intermittent Mandatory Ventilation (SIMV) with the following parameters: RR = 40 breaths/minute; FiO2 0, 40; PIP 18 cm H2O; PEEP 3, 9 cm H2O; MAP 6, 5TI = 0.38 sec and, approx. 20 hours after birth she was extubated due to the improvement of her respiratory insufficiency and hypocapnia (pCO2=25 mmHg ).

A few hours later, while under N-CPAP treatment (+ 4 cm H2O and FiO2 = 0.24), blood began to flow out of the patient’s mouth and, six hours later, there was an unexpected clinical deterioration in her conditions, with desaturation requiring intubation and aggressive mechanical ventilation. Blood flowed copiously out of the endotracheal tube and the radiological picture revealed total opacification of both lung fields compatible with pulmonary hemorrhage (figure 1B).

The coagulation study and the ultrasonographic investigation for a hemodynamically significant Botallo’s duct excluded both diseases as contributory causes to the pulmonary hemorrhage.

The administration by endotracheal route of adrenaline (1:10.000) (0, 1-0, 3 ml/Kg) and surfactant (Curosurf 200mg/Kg x 2) associated with an infusion of fresh frozen plasma (FFP) and concentrated red cells (CRC), followed by conventional and oscillatory (HFO) mechanical ventilation, led to both clinical and radiographical improvements. (figure 1C) shows the chest X-ray immediately after treatment. (figure 2) shows the variations in the oxygenation indices before, during and after treatment.

The neonate was discharged after 95 days without permanent impairment. (figure 1D) shows the chest radiogram performed on the day she was discharged. The follow up 9 months later produced favourable results, with regard to both the respiratory and the neurological outcome.

DISCUSSION

Pulmonary hemorrhage (PH) is a serious complication occurring in VLBW neonates presenting with respiratory distress syndrome (RDS). Before substitution therapy with surfactant was introduced in treatment of severe RDS, PH was a terminal event in neonates who were undersized due to their low gestational age and in asphyctic neonates. After 1990. following the extensive use of exogenous surfactant supplement therapy, an increase in the incidence of this complication was observed. In a meta-analysis study, Raju [1] points out that the risk of PH is approx. 5% in neonates born with RDS and that this risk actually increased, on average, by 47% with the use of any type of surfactant. This increased risk is, however, minimal when compared with the benefits derived from the treatment. The meta-analysis also revealed that low birth weight, the therapeutic strategy and the type of surfactant used could influence the risk of PH unfavourably, while no significant correlation emerged regarding the persistence of Botallo's duct (PDA).

In a retrospective study, M. Tomaszeewska [2] discovered an overall incidence of PH in VLBW neonates of 5.7%; this incidence increased considerably in neonates treated with surfactant compared to controls (91% vs 69%, P=. 005), the gravity of the lung disease being equal. The follow up examination carried out on the PH survivors did not reveal significant differences compared to controls as regards oxygen dependency at 36 weeks, the 3/4 grade of periventricular hemorrhage, the incidence of necrotizing enterocolitis (NEC), periventricular leukomalacia (PVL), PDA and neurological outcome at 20 months.

From the pathophysiological standpoint, the PH was considered as a “hemorrhagic edema" resulting from the fragility of, and stress suffered by, the pulmonary capillaries due to lung overextension, especially during mechanical ventilation. It has been conjectured that after surfactant administration, the vascular resistances, dropping rapidly, permit a rapid left-right shunt through Botallo’s duct, leading to an increased risk of bleeding. Some Authors [3] maintain that predisposing factors such as hypoxia, hypervolemia, congestive cardiac insufficiency, and other lesser known ones, can increase pulmonary capillary pressure and/or interfere with coagulation mechanisms.

In a restrospective study, Pandit [4] demonstrated the efficacy of surfactant therapy in 15 neonates with PH (mean weight: 960 gr, range 595-4045), eight of whom were diagnosed as having RDS and had already been treated with surfactant, three of whom were diagnosed as having meconium aspiration syndrome and four of whom had an isolated PH. The neonates treated showed a marked improvement in oxygenation indices (OI and a/A ratio) with no complications. In a more recent trial, Baier [5] studied the role of inflammation mediators in PH, analysing the serial tracheal aspirate samples of 65 neonates with body weights inferior to 1250 gr, mechanically ventilated due to RDS during the first 21 days of life. Fifteen of these newborn infants developed clinically evident PH. Concentrations of interleukin-8 (IL-8) and cytokine MCP-1 were found to be significantly increased in PH patients and in those with a negative outcome (BPD or death). These data suggest a pathogenic role of IL-8 and MCP- 1 in the unfavourable evolution of the lung disease.

Finally, Amizuka [6] studied the clinical and biochemical factors involved in the onset of PH and in the response to surfactant therapy, in 27 neonates. 33% of the neonates with PH had VLBW, 96% were preterm, 70% had been delivered by Cesarean section and 44% had been intubated in the delivery room. The onset of the PH generally took place one and a half hours after birth. Twenty-six of the neonates were subjected to surfactant therapy within 3 hours of the onset of the PH. The tracheal aspirate samples of these patients were studied in order to determine the concentrations of surfactant protein A (SPA), disaturated phosphatidylcholine (DSPC), albumin and, in vitro, the inhibitory activities of the surfactant. The latter correlates with the low birth weight, the low gestational age, intubation in the delivery room, the early onset of the PH and low levels of SPA and DSPC. The response to surfactant administration was found to be excellent in 82% of the cases (ventilatory index <0, 047) within one hour of treatment.

The case study we have described contains a number of interesting aspects for discussion:

• The onset of PH was unexpected, especially considering the initial clinical and radiological picture of the RDS. The mechanical ventilation was not aggressive, either in terms of duration (20 hours) or in terms of volu/barotrauma (MAP max 6, 5 cm H2O) and it took place when the neonate was under NCPAP treatment. The hypocapnia (25 mmHg PCO2), although short-lived, could suggest overdistension of the lung.
• The response to surfactant administration was sensational, both in terms of improvement in the oxygenation indices (see figure 2) and of improvement in the radiological images.
• The PH is, in any case, still a rare occurrence in VLBW neonates affected by RDS and treated with surfactant. In our case too, we excluded other possible causes of the PH and so it seemed justifiable to correlate this complication with the initial use of the surfactant, as suggested by the other epidemiological data available in literature.

CONCLUSION

We felt it important to report our experience in order to confirm the benefits gained from the use of exogenous surfactant associated with other therapies (encotracheal adrenaline, conventional mechanical ventilation and HFO, FFP, CRC) in order to combat surfactant inhibition and restore normal pulmonary function in neonates affected by PH.

REFERENCES

1. Raju TN, Langenberg P. Pulmonary hemorrhage and exogenous surfactant therapy: a metaanalysis. J Pediatr. 1993 Oct;123(4):603-10
2. Tomaszewska M, Stork E, Minich NM, Friedman H, Berlin S, Hack M. Pulmonary hemorrhage: clinical course and outcomes among very lowbirth- weight infants. Arch Pediatr Adolesc Med. 1999 Jul;153(7):715-21
3. De Carolis MP, Romagnoli C, Cafforio C, Piersigilli F, Papacci P, Vento G, Tortorolo G. Pulmonary haemorrhage in infants with gestational age of less than 30 weeks. Eur J Pediatr. 1998 Dec;157(12):1037-8
4. Pandit PB, Dunn MS, Colucci EA. Surfactant therapy in neonates with respiratory deterioration due to pulmonary hemorrhage. Pediatrics. 1995 Jan;95(1):32-6
5. Baier RJ, Loggins J, Kruger TE. Increased interleukin-8 and monocyte chemoattractant protein-1 concentrations in mechanically ventilated preterm infants with pulmonary hemorrhage. Pediatr Pulmonol. 2002 Aug;34(2):131-7.
6. Amizuka T, Shimizu H, Niida Y, Ogawa Y. Surfactant therapy in neonates with respiratory failure due to haemorrhagic pulmonary oedema. Eur J Pediatr. 2003 Oct;162(10):697-702.
7. Il Surfattante nella Patologia Respiratoria Acuta" Editor Nicola Dirozzi, Daniela Perrotta. Edizione fuori commercio Riservata ai Sigg.Medici SEEd srl in collaborazione con Chiesi Farmaceutici.

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