Interstitial Syndrome And Alveolar Consolidation: Sonographic Markers of Hemodynamic Pulmonary Edema In Infants

Full Text

Background

The last decade was marked by progress in the field of diagnostics of lung diseases, particularly with the use of ultrasound imaging. The accumulation of experience in the use of transthoracic ultrasonography in the diagnostics of a sufficiently wide range of pathology attributed to the competence of internists, surgeons [10], and pediatricians [5, 19]. Moreover, special attention is paid to investigate the possibilities of employing sonography in intensive care units and newborn departments, that is, where diagnostics is required right at the patient’s bed; however, until now, these studies remain at the level of pilot projects [18, 23, 24].

Transthoracic ultrasonography of the lungs is possible because of the presence of extracellular fluid in the lung tissue. Extracellular fluid first makes the alveolar walls thicker (first phase) and then fills the alveoli (second phase) because of inflammatory or hemodynamic edema. In the first phase, the disturbance of the normal air-liquid ratio is visualized as an artifact (reverberation) that represents as linear hyperechogenic signals that can be counted and called comets [3, 4, 6, 9, 14, 15, 17] or B-lines [13, 21]. The emergence of such lines is usually considered as evidence of the so-called interstitial syndrome [12, 16, 22, 23]. During the second phase, the alveoli are filled with liquid, the pulmonary consolidation areas are visualized and counted and are called “alveolar consolidation” [11, 23].

Ultrasonography was repeatedly utilized to determine the state of the lungs in cardiac pathology in adults [7, 8, 20] than in children. This is largely because of the complex features of heart failure formation in early childhood, which in most cases makes it impossible to classify confidently.

The aim of the study is to evaluate the possibilities of using two ultrasonographic phenomena, namely, “al veolar consolidation” and “interstitial syndrome,” in detecting hemodynamic pulmonary edema in congenital heart diseases in young children.

Materials and methods

The study was conducted in the neonatal resuscitation and neonatal departments of Pediatric Department No. 3 of St. Petersburg State Pediatric Medical University.

A formalized card included 179 signs recorded during the course of physical, instrumental, and laboratory studies performed in accordance with current clinical guidelines [1, 2].

Ultrasound examination of the heart and lungs was performed using GE LOGIQ E and Philips HD11 ultrasound scanners with linear, convex, and sector probes at 7-12, 3-5, and 1.7-4.0 MHz, respectively. During the examination, the patient lay in supine position, then in prone position, and, insome cases, in the edgewise position. Diagnostic programs were expanded as part of an in-depth description of lung conditions through ultrasonography. The following sonographic characteristics of the lungs were recorded [10, 19, 24]:

• The area of the consolidated lung sites in mm2 (AirLessTotal), total for all segments.
• The number of B-lines in units (SDtot), total for all lung segments.
• The amplitude of diaphragm excursion, mm (DiafMove)
• The amplitude of lung movement, mm (LungMove)
• The ratio of the amplitudes of the diaphragm excursion and lung movement in units, calculated value (DiafLung)

Overall, 131 pediatric patients of both genders (53% were boys) aged 1-246 days were examined. Because the present study considered the presence of any anatomical possibility of blood exchange between the small and large circulatory systems, the functioning open oval window (OOW) and open arterial duct (OAD) were considered a defect at any age. Table 1 presents the distribution of the pediatric patients examined into groups.

 

Table 1. Total number of pediatric patients examined and their distribution into the diagnosis groups

Таблица 1. Общее количество обследованных детей и их распределение по группам диагнозов

Primary diagnosis	Number of pediatric patients	Age (days)	Number of studies
Total number of the patients examined	131	1-246	240
Number of pediatric patients with congenital heart disease	47	2-246	74
Number of pediatric patients with other pathologies, including: • other pathology + open oval window	84 51	1-130 5-97	91 76

 

The duration of observation and the number of sessions of ultrasound scanning were determined by the severity and dynamics of the child’s condition. Table 2 presents the most common characteristics of the examined patients.

 

Table 2. Brief general description of the patients examined

Таблица 2. Краткая общая характеристика обследованных

Characteristic	Mean value (M)	Average error from М	Range of values
Gestational age at birth (weeks)	33.4	0.3	24-42
Body length at birth (cm)	43.6	0.5	28-59
Body weight at birth (g)	2054	64	640-4650
Apgar 1 (points)	7 (median)	–	1-9
Apgar 5 (points)	7 (median)	–	1-9
Body weight as of the day of examination	2656	76	650-5790

 

In general, the proportion of the pediatric patients with severe condition at the start of the study was approximately 30%.

Table 3 shows the distribution of pediatric patients with cardiac pathologies according to the main diagnoses. The exclusion criteria for pediatric patients in this group are as follows: the presence of pneumonia, meconium aspiration, bronchopulmonary dysplasia, and respiratory distress syndrome.

 

Table 3. Distribution of pediatric patients with cardiac pathology according to the main diagnoses

Таблица 3. Распределение детей с патологией сердца по основным диагнозам

Defect	Age (days) at the time of examination	Number of pediatric patients	Number of studies	Dimensions (mm)
				Max	Min
Only OOW	1-166	57	79	3.7	1.0
OOW in the complex	5-246	30	49	4.2	1.0
Only OAD	8-39	5	8	3.0	1.0
OAD in the complex, including: Closed during the follow-up	2-104 25-97	20 2	36 7	4.5	1.0
				2.0 =>	0.0
Only IASD	9-73	7	8	8.0	2.0
IASD in the complex	9-159	9	14	8.0	3.0
Only IVSD	20-124	8	9	10.0	2.0
IVSD in the complex	2-246	25	38	10.0	1.0
Pulmonary artery stenosis in the complex	10-86	3	7	–	–
Anomalous pulmonary veins drainage in the complex	2-125	2	3	–	–
Примечание: ООО — открытое овальное окно; ОАП — открытый артериальный проток; ДМПП — дефект межпредсердной перегородки; ДМЖП — дефект межжелудочковой перегородки. Note: OOW, open oval window; OAD, open arterial duct; IASD, interatrial septal defect; IVSD, interventricular septal defect

 

In most pediatric patients, the functioning OOW, which in some cases reaches a diameter of 4.2 mm, was determined steadily with discharge of blood from left to right. However, when blood dynamics was observed, only two cases had cessation of blood flow through it.

The presented data reveals that of all the examined pediatric patients, only three had a pulmonary circuit disorder.

OAD was recorded in 53% of the pediatric patients in the cardiological group in a period of 2-104 days, and its closure was recorded in only two patients in the late period. This was because OAD was part of a combination of defects and not a single defect in most cases (see Table 4).

 

Table 4. Variants of the combinations of various defects

Таблица 4. Варианты комбинаций пороков и открытого овального окна

Defect	Age (days)	Number of pediatric patients	Number of studies	Dimensions (mm)
				Max	Min
OOW + OAD	5-104	13	26	4.2 4.0	1.0 1.0
OOW + IVSD	2-246	11	15	4.0 10.0	1.0 1.0
IASD + IVSD	9-159	6	10	8.0 10.0	3.5 3.0
OOW + IVSD + OAD	17-61	3	7	4.0 8.0 4.5	1.0 3.0 1.5
IASD + OAD	77-97	1	2	8 2 => 0.0
IVSD + OAD	46-73	1	3	3.2 3.0
OOW + IVSD + OAD + anomalous pulmonary vein drainage	2	1	1	2.5 2.5 3.0
IASD + IVSD + anomalous pulmonary vein drainage	118-125	1	2	3 7 => 4
OOW + OAD + PAS	10-67	1	4	1.0 2.0 –
IASD + IVSD + PAS	45	1	1	5.0 3.0 –
OOW + IVSD + PAS	58-86	1	2	3.0 8.0 –
Примечание: ООО — открытое овальное окно; ОАП — открытый артериальный проток; ДМПП — дефект межпредсердной перегородки; ДМЖП — дефект межжелудочковой перегородки; СЛА — стеноз легочной артерии. Note: OOW, open oval window; OAD, open arterial duct; IASD, interatrial septal defect; IVSD, interventricular septal defect; PAS, pulmonary artery stenosis

 

Table 5 presents the distribution of pediatric patients without heart and lung disorders. The inclusion criterion of the patients in the comparison group was the absence of history of pathology of the heart and lungs according to clinical, instrumental, and laboratory signs and absence of such pathology at the time of the study.

 

Table 5. Distribution of pediatric patients without heart and lung diseases by diagnoses

Таблица 5. Распределение детей без поражения сердца и легких по диагнозам

Diagnosis	Number of the patients examined	Age (days) at the time of examination	Number of studies
Intra-amniotic infection of the fetus	31	2-97	40
Hypoxic injury of the CNS	32	1-130	51
Diseases of the GIT, moderate hypotrophy	21	1-166	23
Примечание: ЦНС — центральная нервная система; ЖКТ — желудочно-кишечный тракт Note: CNS, central nervous system; GIT, gastrointestinal tract

 

Due to the multifactor data of the phenomena under study, multiple regression analysis and routine parametric estimation methods (Student–Fischer t-test) were used to analyze obtained results. The data was statistically analyzed by the standard tools of Statistica for Windows ver. 6 (StatSoft Inc., No. AX204B521115F60).

Results

An attempt to describe the hemodynamics of the pulmonary circuit with defects are priori known to affect (incomplete drainage of the pulmonary veins) and do not affect (OOW) the filling of the pulmonary circuit through ultrasonography appeared to be successful (see Table 6). Furthermore, no differences were observed between groups of pediatric patients with and without a functioning oval window on the basis of the registered characteristics, despite the fact that the size of the window in a significant proportion of the children was quite large (see Table 3). In incomplete drainage of the pulmonary veins, there was a significant 3.8 times increase in the area of alveolar consolidation (AirLessTotal) (p = 0.045), with no differences in the size of the left atrium, right ventricle, pulmonary artery diameter, blood peak flow, and mean pulmonary artery pressure due to the presence of compensating defects.

 

Table 6. Significance of the characteristics describing interstitial syndrome and alveolar consolidation and pulmonary heart in pediatric patients with an OOW and incomplete drainage of pulmonary veins through ultrasonography

Таблица 6. Значение характеристик, описывающих интерстициальный синдром и альвеолярную консолидацию, а также характеристик правых отделов сердца в терминах ультразвуковой сонографии у детей с открытым овальным окном и неполным дренажом легочных вен

Defect type	Characteristic	Mean value		T	p
		0*	1*
OOW without other defects	AirlessTotal	96.88000	64.97468	1.15164	0.250829
	SDtot	10.70400	9.94937	0.77272	0.440593
	LA	10.53660	10.57568	–0.10054	0.920032
	RV	9.71099	10.10000	–0.64921	0.517238
	PA	7.90408	8.55541	–1.02932	0.304793
	PAVmax	1.30029	1.13615	1.06965	0.286201
	PAP	25.77027	23.11087	1.18104	0.239960
Incomplete drainage of pulmonary veins combined with other defects	AirlessTotal	78.44000	299.0000	–2.02040	0.044669
	SDtot	10.40000	13.0000	–0.65700	0.511934
	LA	10.53472	12.1500	–0.88738	0.376072
	RV	9.84056	10.6667	–0.40327	0.687348
	PA	8.18343	8.2333	–0.02079	0.983440
	PAVmax	1.22556	1.5167	–0.48593	0.627602
	PAP	24.90254	15.8000	1.06322	0.289851
Примечание: 0* — нет дефекта, 1* — есть дефект, выделено существенное различие; LA — диаметр левого предсердия (мм); RV — диаметр правого желудочка (мм); PA — диаметр легочной артерии (мм); PAVmax — максимальная скорость кровотока в легочной артерии (м/с); PAP — среднее давление в легочной артерии (мм Hg). Note: 0*, no defect; 1*, presence of a defect, an essential difference is allocated; LA, diameter of the left atrium (mm); RV, diameter of the right ventricle (mm); PA, diameter of the pulmonary artery (mm); PAV, blood peak flow in the pulmonary artery (m/s); PAP, average pressure in the pulmonary artery (mm Hg); OOW, open oval window

 

Considering that the sample had a large number of complex defects, multiple linear regression modeling (stepwise inclusion) was performed, with a preliminary choice of factors at the level of interconnection not exceeding 0.4. A total of 19 models were created with explained dispersion level of 35%-82% with the included characteristics, namely, AirLessTotal, SDtot, LungMove, and DiafMove, treated in combination and individually. Tables 7 and 8 show the results of the modeling using SDtot and RV characteristics, control, physical, and laboratory characteristics, as well as characteristics of the heart and right lung segment in terms of ultrasonography. The regression of coefficients equation presented in Table 7, which shows an insignificant correlation of the characteristics (Durbin–Watson correlation coefficient of 0.26), provide 78% of the explained dispersion of the SDtot characteristic value, thereby reflecting the severity of the interstitial syndrome.

 

Table 7. Results of the regression modeling of the SDtot characteristic value. Regression summary for dependent variable: SDtot (ivan_data_w9), R = 0.93244324, R = .93244324 R2 = .86945039 Adjusted R2 = .76263707 F(9,11) = 8.1399 p < .00099 Std. Error of estimate: 2.4241 Durbin-Watson d =1.472474, Serial Corr. 0.263094

Таблица 7. Результаты регрессионного моделирования значения характеристики SDtot. Regression Summary for Dependent Variable: SDtot (ivan_data_w9), R = .93244324 R2 = .86945039 Adjusted R2 = .76263707 F(9,11) = 8.1399 p < .00099 Std. Error of estimate: 2.4241 Durbin-Watson d =1.472474, Serial Corr. 0.263094

Characteristics studied	BETA	Std. Err. of BETA	B	Std. Err. of BETA	p-level
Intercept			100.0492	19.64767	0.000348
m	–0.856598	0.259351	–0.0041	0.00125	0.007042
CardRate	–0.992885	0.167861	–0.6257	0.10579	0.000101
AirLessTotal	0.316251	0.130543	0.0523	0.02160	0.033851
PAVmax	–0.237113	0.130261	–7.3759	4.05203	0.096003
pO2	–0.107595	0.141044	–0.0469	0.06149	0.461603
PA	–0.659042	0.233702	–2.9361	1.04117	0.016667
RespRate	0.405810	0.161775	0.6498	0.25902	0.029065
DiafLung	0.280194	0.133050	2.0494	0.97313	0.058991
mass	0.425926	0.321814	0.0022	0.00163	0.212513
Примечание: m — масса тела при рождении (г); CardRate — частота сердечных сокращений в момент исследования (1/мин); pO2 — напряжение кислорода в плазме крови в момент исследования (мм Hg); RespRate — частота дыханий в момент исследования (1/мин); mass — масса тела в момент исследования (г); прочие обозначения — см. пояснения к табл. 6 и в тексте, выделены существенные значения. Note: m, birth weight (g); CardRate, the heart rate at the time of the study (1/min); PO, oxygen tension in blood plasma at the time of the study (mm Hg); RespRate, respiration rate at the time of the study (1/min); mass, body mass at the time of the study (d); other designations, see the explanations to Table 6 and in the text; the significant values are highlighted

 

The negative coefficients with statistically significant characteristics for m, CardRate, and PA, which indicate that the SDtot value is greater in pediatric patients born with a low body weight and who have bradycardia with a small pulmonary artery diameter at the time of examination, is of particular interest. Together with the positive coefficients for the AirLessTotal and RespRate characteristics, the model correctly describes the known fundamental regularities, and the coefficient values indicate that pulmonary artery diameter greatly contributed to the formation of the interstitial syndrome compared to the birth weight.

Table 8 presents the coefficients of the characteristics of the regression equation that determines the size of the right ventricle. In accordance with classical notions of physiology, it was assumed that the interstitial syndrome and alveolar consolidation, with their sufficient severity and duration,affect the size of the right ventricle on a par with, for example, the effect of the size of the septal defects. The coefficients of the regression equation presented in Table 8, with a moderate interrelation of characteristics (Durbin–Watson correlation coefficient of 0.37) indicated 42% of the explained dispersion of the RV characteristic value.

 

Table 8. Results of the regression modeling of the RV characteristic value. Regression summary for dependent variable: RV (ivan_data_w9) R = .69223739 R2 = .47919260 Adjusted R2 = .41932968 F(10,87) = 8.0048 p < .00000 Std. Error of estimate: 2.1761 Durbin-Watson d = 1.263156, Serial Corr. 0.3680869

Таблица 8. Результаты регрессионного моделирования значения характеристики RV. Regression Summary for Dependent Variable: RV (ivan_data_w9) R = .69223739 R2 = .47919260 Adjusted R2 = .41932968 F(10,87) = 8.0048 p < .00000 Std. Error of estimate: 2.1761 Durbin-Watson d = 1.263156, Serial Corr. 0.3680869

Исследуемые характеристики	BETA	Std. Err. of BETA	B	Std. Err. of BETA	p-level
Intercept			1.230303	1.595912	0.442850
M	0.238464	0.099291	0.000708	0.000295	0.018449
PAP	0.312879	0.085093	0.093431	0.025410	0.000408
LA	0.272323	0.094498	0.300839	0.104394	0.004980
SDtot	0.316294	0.105903	0.146247	0.048967	0.003664
OAD	–0.200700	0.084468	–0.618692	0.260388	0.019695
OOO	0.245074	0.086941	0.572891	0.203234	0.005966
DMPP	0.189365	0.089900	0.430067	0.204173	0.038051
PA	–0.158417	0.080136	–0.087918	0.044474	0.050225
AirLessTotal	–0.202964	0.099895	–0.003599	0.001771	0.045227
Days	0.167797	0.092230	0.013347	0.007337	0.072302
Примечание: OAD — диаметр функционирующего артериального протока (мм); ООО — диаметр функционирующего овального окна в комплексе дефектов (мм); DMPP — диаметр дефекта межпредсердной перегородки (мм); Days — день жизни на момент обследования; прочие обозначения — см. пояснения к табл. 6, 7 и в тексте, выделены существенные значения. Note: OAD, diameter of the functioning arterial duct (mm); OOO, diameter of the functioning oval window in the complex of defects (mm); DMPP, diameter of interatrial septal defect (mm); Days, the day of life at the time of the examination; other designations, see the explanations in Tables 6 and 7 and in the text; the significant values are highlighted

 

Apparently, ultrasonographic characteristics reflecting the interstitial syndrome and alveolar consolidation reliably determine the size of the right ventricle.

The negative coefficient for the OAD characteristic is explained by the fact that a significant number of OAD, such as 7 of 12 without taking into account the complex with an OOW (see Table 4), were involved in complex defects for which a decrease in the discharge along the duct leads to an increase in blood flow in another defect. This also explains the effect of the diameter of the oval window. The negative coefficient in the PA characteristic is natural, and the negative coefficient in the AirLessTotal characteristic has no explanation and requires additional study using detailed measurement of the pressures within the cardiac chambers.

Discussion

Our results confirm the expediency of using the descriptions of interstitial syndrome and alveolar consolidation in terms of ultrasonography to assess the severity of hemodynamic pulmonary edema in young children.

The frequency of inclusion of SDtot and AirLessTotal characteristics in regression models that describe the state of children’s lungs with congenital heart diseases through indirect signs is extremely high.

SDtot (more often) and AirLessTotal (less often) characteristics were included in almost all models, and the results of the modeling almost always corresponded to the classical notions of clinical physiology in describing the hemodynamics of the pulmonary circuit. The rare inclusion of DiafMove, LungMove, and DiafLung characteristics in the models was somewhat surprising, which can be partly explained by the low extensibility of the lungs at this age and the fact that the diaphragm is of less importance in organizing external respiration in infants.

The rarer inclusion of the AirLessTotal characteristic can be explained by technical difficulties in calculating the consolidation area, which resulted in a larger error, as well as by the small number of pediatric patients with consolidation, because the number of pediatric patients with the firstphase of edema at such an early age significantly exceeds the number of pediatric patients with a second phase of edema.

The disadvantage of the model, which equation is presented in Table 7, is that it includes all control characteristics, with the exception of body weight and, in a less degree, the diameter of the pulmonary artery, and the period of variability in time is minutes/hours. At the same time, the period of change in the pronouncement of the controlled variable, which is the interstitial syndrome, is much longer (in days). This implies a high proportion of randomness in obtaining the values of the coefficients in such a combination. The model, which characteristics and coefficients of the equation are presented in Table 8, partly eliminates this disadvantage because the variability period of controlled and controlling variables are approximated to comparable quantities.

Conclusions

1. Interstitial edema and alveolar consolidation, described in terms of transthoracic ultrasonography, should be used as markers of hemodynamic disorders of the pulmonary circuit in congenital malformations in children at an early age.
2. The characteristics of interstitial edema and alveolar consolidation are reliably associated with clinical, laboratory, and instrumental signs of the pulmonary circuit.

Therefore, additional studies are required to develop the decisive rules for differential diagnostics of various types and stages of hemodynamic disorders of the pulmonary circuit and to determine diagnostic errors when using transthoracic ultrasonography as well as the measurement of pressures within the heart cavities and large vessels.

About the authors

Ahlam A. Mohammad

St Petersburg State Pediatric Medical University

Author for correspondence.
Email: d.ahlam@mail.ru

Postgraduate Student, Department of Hospital Pediatrics

Russian Federation, Saint Petersburg

Ivan I. Akinshin

St Petersburg State Pediatric Medical University

Email: akinshinivan87@gmail.com

Postgraduate Student, Department of Radiology and Biomedical Imaging Faculty of Postgraduate Education

Russian Federation, Saint Petersburg

Elena V. Sinelnikova

St Petersburg State Pediatric Medical University

Email: sinelnikavae@gmail.com

MD, PhD, Dr Med Sci, Professor, Head, Department of Radiology and Biomedical Imaging Faculty of Postgraduate Education

Russian Federation, Saint Petersburg

Alla J. Rotar

St Petersburg State Pediatric Medical University

Email: a_lepenchuk@mail.ru

Student, Department of Radiology and Biomedical Imaging Faculty of Postgraduate Education

Russian Federation, Saint Petersburg

Vyacheslav G. Chasnyk

St Petersburg State Pediatric Medical University

Email: chasnyk@gmail.com

MD, PhD, Dr Med Sci, Professor, Head, Department of Hospital Pediatrics

Russian Federation, Saint Petersburg

Irina V. Solodkova

St Petersburg State Pediatric Medical University

Email: isolodkova@mail.ru

MD, Associate professor, Chair of Hospital Pediatrics

Russian Federation, Saint Petersburg

Elena V. Baryshek

St Petersburg State Pediatric Medical University

Email: barishek@yandex.ru

MD, Professor, Chair of Hospital Pediatrics

Russian Federation, Saint Petersburg

References

Supplementary files