Neonatal pneumothoraces with atypical location: the role of lung ultrasound

Neonatal pneumothorax (NP) is a potentially life-threatening condition. Lung ultrasound (LUS) has shown higher sensitivity and specificity in diagnosis compared to x-rays, but evidence regarding its usefulness in complex NP is lacking. We report four neonates suffering from cardiac or esophageal malformations who developed lateral and/or posterior pneumothoraces, in which LUS helped, making NP diagnosis and management easier and faster. Conclusion: LUS is an easy-to-use, fast, simple, and accurate tool when evaluating newborns with NP, also in atypical positions such as in surgical patients. What is Known: • Lung ultrasound (LUS) has higher sensitivity and specificity than x-rays in the diagnosis of pneumothorax in neonatal patients. What is New: • This is the first report about neonatal pneumothorax in non-conventional areas (lateral/posterior) diagnosed by lung ultrasound and how obtaining this information is critical in order to optimize management. What is Known: • Lung ultrasound (LUS) has higher sensitivity and specificity than x-rays in the diagnosis of pneumothorax in neonatal patients. What is New: • This is the first report about neonatal pneumothorax in non-conventional areas (lateral/posterior) diagnosed by lung ultrasound and how obtaining this information is critical in order to optimize management.


Introduction
Pneumothorax is a life-threatening condition, defined by the presence of air between the two pleural layers. Its prevalence in the neonatal population has been described as 1-6%, increasing with decreasing gestational age [1]. Lung ultrasound (LUS) has demonstrated higher sensitivity and specificity than conventional x-rays for the diagnosis of pneumothorax in children and neonates [1][2][3][4], with GRADE B evidence, according to the latest European Society of Pediatric and Neonatal Intensive Care guidelines regarding point-of-care ultrasound use [5].
In the critically ill, pneumothoraces are usually located in the anterior area of the thorax. However, in cardiac and thoracic surgery patients or when several drainage procedures are needed, they can be located in non-conventional areas, making assessment and drainage difficult, when based solely on x-rays, even when using lateral views.
We aim to describe several neonatal pneumothoraces (NP) with atypical locations, assessed using LUS, in four patients.

Material and methods
Retrospective review of the LUS and x-ray images of four patients with NP with atypical locations (in the lateral or posterior area of the chest, not involving the anterior area) and their management in two tertiary neonatal intensive care units (NICUs) in Spain (Gregorio Marañón University Hospital and Puerta del Mar University Hospital). In both centers, LUS has been used for more than 5 years to study the respiratory condition of admitted sick neonates. The study period was from January to March 2021 and it was approved by the Gregorio Marañón Hospital Research and Ethics Committee with a waiver of informed consent, and was performed in accordance with the Declaration of Helsinki and its later amendments.
LUS was performed by experienced neonatologists as part of the daily care of the patients requiring respiratory support in the NICU, using a Sonosite iViz or a General Electric Vivid IQ ultrasound device, both with linear probe, using lung presets. The focus was positioned at the pleural line, depth was set at 4 cm, and no harmonics were used. In every case, 6 areas were evaluated: midclavicular line, anterior, and posterior axillary lines in each hemithorax, with the patient in supine position. X-ray images were provided by a pediatric radiologist, who was unaware of the results of the LUS. The images (clips and pictures) were stored in the ultrasound machine as they were obtained. CARE guidelines (for CAse REports) have been followed to organize this manuscript [6].

Results
A summary of the clinical condition and epidemiologic data of the infants included in this manuscript is provided in Table 1.

Patient 1
Late preterm male newborn with type I esophageal atresia requiring multiple thoracoscopic surgical interventions due to a long-gap atresia. Eight days after the last intervention, he suffered a right tension pneumothorax and required a chest drain in the second intercostal space at the midclavicular line. Two days later, he developed acute respiratory distress despite endotracheal intubation and mechanical ventilation. In LUS, a hydropneumothorax was observed in the lateral area of right lung despite the previous drainage. The two were related to anastomotic dehiscence. Posteroanterior (PA) x-ray confirmed NP but no evidence of pleural effusion. A new ultrasound-guided chest tube was inserted via the seventh intercostal space, obtaining 20 ml of pleural effusion and air, which resolved the respiratory distress. See Fig. 1 and supplementary material 1 (SM 1).  line. However, no air was obtained. LUS identified normal pattern in the anterior area and located the pneumothorax between anterior and posterior axillary lines, so respiratory support could be optimized (repositioning, volume guarantee increased) and close clinical and ultrasound follow-up was carried out. NP spontaneously resolved without drainage and respiratory situation improved progressively. See Fig. 1 and SM 2.

Patient 3
Late male preterm infant on mechanical ventilation since birth because of severe pulmonary hypoplasia and congenital hypotonia due to myotonic dystrophy type 1. He needed several drainage procedures because of repeated pneumothoraces in his right lung. At 11 DOL, a pneumothorax between anterior and posterior axillary lines was detected during a control LUS, but anterior air and clinical worsening were not observed. Serial LU showed progressive worsening of air leak (lung point moved towards anterior area) along with respiratory deterioration, so finally the thoracic drain was reinserted 15 h after the first LUS, with subsequent resolution of the pneumothorax, according to LUS and x-ray images. See Fig. 2 and SM 3.

Patient 4
Late male preterm infant with type III esophageal atresia corrected on the second DOL. On the eighth DOL, he developed sudden respiratory and hemodynamic deterioration due to a NP in the right hemithorax, despite the previously inserted surgical drainage. It was successfully drained using a new chest tube via the fourth intercostal space. Two days later, the NP could still be seen on x-ray images, so an anterior thoracocentesis was performed with the aim of achieving successful extubation, but the NP was not resolved. LUS showed a NP in the posterior and lateral areas of the left thorax, with lateral subcutaneous emphysema and lateral x-rays confirmed this location ( Fig. 2 and SM 4). This finding avoided a new pleural drain, and the NP resolved

PATIENT 3 Xrays
Lung ultrasound Anterior Lateral P osterior

PATIENT 4 Xrays
Lung ultrasound Anterior Lateral P osterior spontaneously, without specific treatment. The chest drain was finally removed after 12 days, because the infant also suffered secondary chylothorax.

Discussion
These cases highlight the importance of evaluating NP using LUS in the critically ill neonate in order to better assess its volume and plan management, particularly with surgical patients or those with several drainage interventions.
We have reported 4 neonates with complex diagnoses. All had in common prior manipulation of the chest (cardiac/ esophageal surgery or previously inserted pleural drainage). LUS optimized management in all of them: In patient 1, detailing the amount of pleural effusion and air (even better than x-rays), and permitting an ultrasound-guided technique. In patients 2 and 4, demonstrating that anterior thoracocentesis is not always the best solution. In patients 2 to 4, it permitted dynamic, close control of evolution in order to decide on the best therapeutic approach.
LUS is an easy-to-use examination, which is quick, cheap, free of ionizing radiation, and can be performed by the same clinician attending the patient [7]. Several studies have demonstrated a steep learning curve; shorter than for other uses of point-of-care ultrasound [8].
Classically, chest x-ray has been the gold standard for diagnosis in the sick newborn with respiratory diseases. However, LUS has demonstrated a higher sensitivity and specificity in several diseases, and the typical patterns of almost all neonatal lung diseases have already been described [5,9].
Typical findings of pneumothorax in LUS are A-lines pattern, absence of lung sliding B-lines, and lung pulse (SM 4), together with lung point identification (SM 2, SM 3). The latter has a 100% specificity, and it should be systematically identified in order to confirm the diagnosis [4]. Stratosphere sign on M-mode ( Figs. 1 and 2), as a surrogate sign of the absence of pleural sliding, can be identified [10,11]. Experience is needed in order to rule out some ultrasonographic findings which could be misinterpreted [12].
In the critically ill patient, in supine position, the air is usually located in the anterior part of the chest and, as the amount of air increases, the lung point moves towards the patient's back, until its disappearance in massive pneumothoraces [13]. However, in our cases, no air was identified in the anterior area, and instead, two lung points were seen, limiting the pneumothorax to the lateral/posterior area. We hypothesized that, in the event of worsening, each lung point would move towards anterior and posterior areas, respectively, although this assumption has not been analyzed previously, to the best of our knowledge. This double lung point has been previously reported in 3 adults and one child with bubble pneumothorax [14,15]. Outcomes are diverse, but two of them absorbed spontaneously and one was not resolved with anterior thoracocentesis, as we reported. There are no similar data on critically ill neonates as ours.
This kind of NP with atypical location in the lateral or posterior area of the chest can occur when interventions have been previously performed on the thorax (cardiac surgery, pleural drainage, etc.), leading to pleural adherences that limit the free movement of the air between the two layers. In x-rays, this fact can be difficult to assess, due to the "2-dimensional image" obtained, unless performing an x-ray with lateral views (exposing the child to extra radiation and often risky manipulation). However, this task is very easy to achieve using LUS, defining the precise location of the lung point, reducing radiation, and increasing the safety of the procedures performed in newborns, such as emergent thoracocentesis and drainage insertion [7,[16][17][18]. In cases 2 and 4, anterior thoracocentesis was performed before LUS, not resolving the NP and exposing the child to extra risk. LUS allowed monitoring the air leak and its evolution along time.
In addition to studying its location, LUS is useful for checking pneumothorax resolution following pleural drainage insertion, and to serially confirm evolution before removal [4]: its use has also been related to shortened hospital stays in newborns [18]. In our experience, it is a useful instrument for monitoring the patient and anticipating any clinical deterioration.
In conclusion, this study stresses the importance of LUS in the management of a neonate with suspected pneumothorax, particularly in complex patients with previous thoracic manipulation, as previously described in some clinicalultrasound protocols such as SAFE (Sonographic Assessment of liFe-threatening Events) algorithm [7].
Long experience of researchers in the use of LUS and retrospective analysis are potential limitations of this study; however, we consider that the results are relevant and objective, and create an interesting area for further research.
More studies are needed in order to confirm our findings and hypothesis, so a better understanding of pneumothorax physiopathology in this critical population can be described.

Authors' contributions
All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Rebeca Gregorio-Hernández, Alba Pérez-Pérez, and Almudena Alonso-Ojembarrena. The first draft of the manuscript was written by Rebeca Gregorio-Hernández and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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