Effects of early mechanical ventilation on the morphology and function of the diaphragm in children

doi:10.3969/j.issn.1674-8115.2022.12.009

Abstract

Abstract:

Objective ·To investigate the morphologic and functional changes of the diaphragm of children during early mechanical ventilation under synchronized intermittent mandatory ventilation (SIMV) mode. Methods ·Children were admitted to the Pediatric Intensive Care Unit (PICU) of Xinhua Hospital, Shanghai Jiao Tong University School of Medicineand received mechanical ventilation for at least 96 h from October 2020 to December 2021. Bedside ultrasonic testing was conducted to inspect the changes in the diaphragm at three different time points (0, 48, and 96 h, respectively). Kruskal-Wallis H test was conducted for examining the abdominal fat thickness, atrophy rate, diaphragm thickness and DE between the groups. The diaphragm thickness was further compared by Bonferroni's test for ex-post hoc comparisons. Univariate ANOVA was performed for analyzing the diaphragm contraction velocity, diaphragm thickening fraction and diaphragmatic atrophy rate between the groups. Results ·Forty-six children in PICU with complete measurement data were included. Their average age was 2.94 (1.35, 7.00) years, including 23 males and 23 females. The main disease leading to perform mechanical ventilation was pneumonia (52.17%). There was no significant difference between the choice of ventilator parameters and oxygenation status during the observation period (P>0.05). In the early stage of mechanical ventilation (within 96 h), 50% of children showed atrophy of abdominal subcutaneous fat, 36.96% showed nutritional disorders (fasting and need parenteral nutrition support), and 93.5% of children received glucocorticoid therapy. However, there was no significant difference in the atrophy degree of abdominal subcutaneous fat between the three time points (all P>0.05). Bedside ultrasonography detected significant atrophy of bilateral diaphragm thickness at three different time points (all P=0.000). After 48 h of mechanical ventilation, the atrophy rate of the right diaphragm was 4.27%±7.36%, and the left diaphragm was 3.88%±6.85%. After 96 h of ventilation, the atrophy rate of the right diaphragm was 7.69%±7.74%, and the atrophy rate of the left diaphragm came to 7.55%±7.69%. The atrophy rate of the bilateral diaphragm was significantly higher in the first 48 h of mechanical ventilation than in the 48 h to 96 h (all P =0.000). However, there were no statistically significant differences in changes of diaphragm function-related indicators (diaphragm excursion, diaphragm contraction velocity, and diaphragm thickening fraction). Conclusion ·The bedside ultrasound is a proven tool to detect diaphragmatic atrophy in mechanically ventilated children. Mechanical ventilation can induce structural atrophy of the diaphragm in children during early mechanical ventilation under SIMV mode, which is more pronounced in the first 48 h. However, the early morphological changes of the diaphragm have not affected its function.

Key words: children, diaphragm, muscular atrophy, mechanical ventilation, ultrasonography

CLC Number:

R725.6

WEI Yifan, ZHU Yueniu, KONG Xiangmei, XU Yaya, ZHU Xiaodong. Effects of early mechanical ventilation on the morphology and function of the diaphragm in children[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022, 42(12): 1712-1719.

Figures/Tables 5

TrendMD

References 45

1	TOBIN M J, LAGHI F, JUBRAN A. Narrative review: ventilator-induced respiratory muscle weakness[J]. Ann Intern Med, 2010, 153(4): 240-245.
2	DE JONGHE B, BASTUJI-GARIN S, DURAND M C, et al. Respiratory weakness is associated with limb weakness and delayed weaning in critical illness[J]. Crit Care Med, 2007, 35(9): 2007-2015.
3	DEMOULE A, MOLINARI N, JUNG B, et al. Patterns of diaphragm function in critically ill patients receiving prolonged mechanical ventilation: a prospective longitudinal study[J]. Ann Inten Care, 2016, 6(1): 75.
4	BÉDUNEAU G, PHAM T, SCHORTGEN F, et al. Epidemiology of weaning outcome according to a new definition. the WIND study[J]. Am J Respir Crit Care Med, 2017, 195(6): 772-783.
5	DRES M, DUBÉ B P, MAYAUX J, et al. Coexistence and impact of limb muscle and diaphragm weakness at time of liberation from mechanical ventilation in medical intensive care unit patients[J]. Am J Respir Crit Care Med, 2017, 195(1): 57-66.
6	KIM W Y, SUH H J, HONG S B, et al. Diaphragm dysfunction assessed by ultrasonography: influence on weaning from mechanical ventilation[J]. Crit Care Med, 2011, 39(12): 2627-2630.
7	GOLIGHER E C, DRES M, FAN E, et al. Mechanical ventilation-induced diaphragm atrophy strongly impacts clinical outcomes[J]. Am J Respir Crit Care Med, 2018, 197(2): 204-213.
8	DAMUTH E, MITCHELL J A, BARTOCK J L, et al. Long-term survival of critically ill patients treated with prolonged mechanical ventilation: a systematic review and meta-analysis[J]. Lancet Respir Med, 2015, 3(7): 544-553.
9	GROSU H B, LEE Y I, LEE J, et al. Diaphragm muscle thinning in patients who are mechanically ventilated[J]. Chest, 2012, 142(6): 1455-1460.
10	LEVINE S, NGUYEN T, TAYLOR N, et al. Rapid disuse atrophy of diaphragm fibers in mechanically ventilated humans[J]. N Engl J Med, 2008, 358(13): 1327-1335.
11	POWERS S K, SHANELY R A, COOMBES J S, et al. Mechanical ventilation results in progressive contractile dysfunction in the diaphragm[J]. J Appl Physiol (1985), 2002, 92(5): 1851-1858.
12	JABER S, PETROF B J, JUNG B, et al. Rapidly progressive diaphragmatic weakness and injury during mechanical ventilation in humans[J]. Am J Respir Crit Care Med, 2011, 183(3): 364-371.
13	SHANELY R A, ZERGEROGLU M A, LENNON SL, et al. Mechanical ventilation-induced diaphragmatic atrophy is associated with oxidative injury and increased proteolytic activity[J]. Am J Respir Crit Care Med, 2002, 166(10): 1369-1374.
14	GOLIGHER E C, FAN E, HERRIDGE M S, et al. Evolution of diaphragm thickness during mechanical ventilation. impact of inspiratory effort[J]. Am J Respir Crit Care Med, 2015, 192(9): 1080-1088.
15	OROZCO-LEVI M, LLORETA J, MINGUELLA J, et al. Injury of the human diaphragm associated with exertion and chronic obstructive pulmonary disease[J]. Am J Respir Crit Care Med, 2001, 164(9): 1734-1739.
16	GOLIGHER E C, LAGHI F, DETSKY M E, et al. Measuring diaphragm thickness with ultrasound in mechanically ventilated patients: feasibility, reproducibility and validity[J]. Intensive Care Med, 2015, 41(4): 642-649.
17	FAYSSOIL A, BEHIN A, OGNA A, et al. Diaphragm: pathophysiology and ultrasound imaging in neuromuscular disorders[J]. J Neuromuscul Dis, 2018, 5(1): 1-10.
18	FARIAS J A, FRUTOS F, ESTEBAN A, et al. What is the daily practice of mechanical ventilation in pediatric intensive care units? A multicenter study[J]. Intensive Care Med, 2004, 30(5): 918-925.
19	TAKAZAKURA R, TAKAHASHI M, NITTA N, et al. Diaphragmatic motion in the sitting and supine positions: healthy subject study using a vertically open magnetic resonance system[J]. J Magn Reson Imaging, 2004, 19(5): 605-609.
20	YAMAGUTI W P, PAULIN E, SHIBAO S, et al. Ultrasound evaluation of diaphragmatic mobility in different postures in healthy subjects[J]. J Bras Pneumol, 2007, 33(4): 407-413.
21	VIVIER E, MEKONTSO DESSAP A, DIMASSI S, et al. Diaphragm ultrasonography to estimate the work of breathing during non-invasive ventilation[J]. Intensive Care Med, 2012, 38(5): 796-803.
22	MATAMIS D, SOILEMEZI E, TSAGOURIAS M, et al. Sonographic evaluation of the diaphragm in critically ill patients. Technique and clinical applications[J]. Intensive Care Med, 2013, 39(5): 801-810.
23	MCCOOL F D, CONOMOS P, BENDITT J O, et al. Maximal inspiratory pressures and dimensions of the diaphragm[J]. Am J Respir Crit Care Med, 1997, 155(4): 1329-1334.
24	COHN D, BENDITT J O, EVELOFF S, et al. Diaphragm thickening during inspiration[J]. J Appl Physiol (1985), 1997, 83(1): 291-296.
25	LIU Y Y, LI L F. Ventilator-induced diaphragm dysfunction in critical illness[J]. Exp Biol Med (Maywood), 2018, 243(17/18): 1329-1337.
26	POWERS S K, WIGGS M P, SOLLANEK K J, et al. Ventilator-induced diaphragm dysfunction: cause and effect[J]. Am J Physiol Regul Integr Comp Physiol, 2013, 305(5): R464-R477.
27	POWERS S K, KAVAZIS A N, LEVINE S. Prolonged mechanical ventilation alters diaphragmatic structure and function[J]. Crit Care Med, 2009, 37(10 Suppl): S347-S353.
28	SCHEPENS T, VERBRUGGHE W, DAMS K, et al. The course of diaphragm atrophy in ventilated patients assessed with ultrasound: a longitudinal cohort study[J]. Crit Care, 2015, 19: 422.
29	IJLAND M M, LEMSON J, VAN DER HOEVEN J G, et al. The impact of critical illness on the expiratory muscles and the diaphragm assessed by ultrasound in mechanical ventilated children[J]. Ann Intensive Care, 2020, 10(1): 115.
30	GLAU C L, CONLON T W, HIMEBAUCH A S, et al. Progressive diaphragm atrophy in pediatric acute respiratory failure[J]. Pediatr Crit Care Med, 2018, 19(5): 406-411.
31	JOHNSON R W, NG K W P, DIETZ A R, et al. Muscle atrophy in mechanically-ventilated critically ill children[J]. PLoS One, 2018, 13(12): e0207720.
32	LEE E P, HSIA S H, HSIAO H F, et al. Evaluation of diaphragmatic function in mechanically ventilated children: an ultrasound study[J]. PLoS One, 2017, 12(8): e0183560.
33	GRASSI A, FERLICCA D, LUPIERI E, et al. Assisted mechanical ventilation promotes recovery of diaphragmatic thickness in critically ill patients: a prospective observational study[J]. Crit Care, 2020, 24: 85.
34	ZAMBON M, BECCARIA P, MATSUNO J, et al. Mechanical ventilation and diaphragmatic atrophy in critically ill patients: an ultrasound study[J]. Crit Care Med, 2016, 44(7): 1347-1352.
35	POWERS S K, DECRAMER M, GAYAN-RAMIREZ G, et al. Pressure support ventilation attenuates ventilator-induced protein modifications in the diaphragm[J]. Crit Care, 2008, 12(6): 191.
36	DEVOTO G, GALLO F, MARCHELLO C, et al. Prealbumin serum concentrations as a useful tool in the assessment of malnutrition in hospitalized patients[J]. Clin Chem, 2006, 52(12): 2281-2285.
37	JIANG J R. Ultrasonographic evaluation of liver/spleen movements and extubation outcome[J]. Chest, 2004, 126(1): 179-185.
38	SUMMERHILL E M, EL-SAMEED Y A, GLIDDEN T J, et al. Monitoring recovery from diaphragm paralysis with ultrasound[J]. Chest, 2008, 133(3): 737-743.
39	DININO E, GARTMAN E J, SETHI J M, et al. Diaphragm ultrasound as a predictor of successful extubation from mechanical ventilation[J]. Thorax, 2014, 69(5): 423-427.
40	FARGHALY S, HASAN A A. Diaphragm ultrasound as a new method to predict extubation outcome in mechanically ventilated patients[J]. Aust Crit Care, 2017, 30(1): 37-43.
41	GOTTESMAN E, MCCOOL F D. Ultrasound evaluation of the paralyzed diaphragm[J]. Am J Respir Crit Care Med, 1997, 155(5): 1570-1574.
42	ZAMBON M, GRECO M, BOCCHINO S, et al. Assessment of diaphragmatic dysfunction in the critically ill patient with ultrasound: a systematic review[J]. Intensive Care Med, 2017, 43(1): 29-38.
43	NEWTH C J L, VENKATARAMAN S, WILLSON D F, et al. Weaning and extubation readiness in pediatric patients[J]. Pediatr Crit Care Med, 2009, 10(1): 1-11.
44	DOORDUIN J, VAN HEES H W H, VAN DER HOEVEN J G, et al. Monitoring of the respiratory muscles in the critically ill[J]. Am J Respir Crit Care Med, 2013, 187(1): 20-27.
45	CATTAPAN S E, LAGHI F, TOBIN M J. Can diaphragmatic contractility be assessed by airway twitch pressure in mechanically ventilated patients? [J]. Thorax, 2003, 58(1): 58-62.

Indicator	M（Q₁， Q₃）/n（%）
General data
Age/year	2.94 （1.35， 7.00）
Male/female/n（%）	23 （50.00）/23 （50.00）
Height/cm	97.50 （78.00， 115.00）
Weight/kg	13.08 （10.00， 22.00）
BMI/（kg·m^-2）	15.94 （13.55， 17.85）
Baseline abdominal fat thickness/mm	0.70 （0.57， 0.89）
Abdominal fat atrophy/n（%）	23 （50.00）
Body surface area/m²	0.60 （0.43， 0.87）
Clinical score system
PCIS	88.00 （79.00， 94.00）
PRISM Ⅲ	6.00 （3.00， 10.00）
Primary disease
Respiratory diseases/n（%）	10 （21.74）
Neurological diseases/n（%）	20 （43.48）
Hematologic diseases/n（%）	4 （8.70）
Digestive diseases/n（%）	5 （10.87）
Musculoskeletal diseases/n（%）	1 （2.17）
Urinary diseases/n（%）	1 （2.17）
Endocrine diseases/n（%）	5 （10.87）
Etiology
Pneumonia/n（%）	24 （52.17）
CNS lesions/n（%）	16 （34.78）
Septic pyemia/n（%）	6 （13.04）
Complication
MODS/n（%）	6 （13.04）
Treatment
Glucocorticoid/n（%）	43 （93.50）
Parenteral nutrition/n（%）	7 （15.22）
Fasting/n（%）	10 （21.74）
Surgical interventions/n（%）	26 （56.52）
Prognosis
Weaning failure/n（%）	18 （39.13）
Mortality in PICU/n（%）	10 （21.74）
Duration of mechanical ventilation/d	8.00 （7.00， 12.00）
Hospitalization days in PICU/d	20.00 （11.00， 31.00）

Indicator	M（Q₁， Q₃）/n（%）
General data
Age/year	2.94 （1.35， 7.00）
Male/female/n（%）	23 （50.00）/23 （50.00）
Height/cm	97.50 （78.00， 115.00）
Weight/kg	13.08 （10.00， 22.00）
BMI/（kg·m^-2）	15.94 （13.55， 17.85）
Baseline abdominal fat thickness/mm	0.70 （0.57， 0.89）
Abdominal fat atrophy/n（%）	23 （50.00）
Body surface area/m²	0.60 （0.43， 0.87）
Clinical score system
PCIS	88.00 （79.00， 94.00）
PRISM Ⅲ	6.00 （3.00， 10.00）
Primary disease
Respiratory diseases/n（%）	10 （21.74）
Neurological diseases/n（%）	20 （43.48）
Hematologic diseases/n（%）	4 （8.70）
Digestive diseases/n（%）	5 （10.87）
Musculoskeletal diseases/n（%）	1 （2.17）
Urinary diseases/n（%）	1 （2.17）
Endocrine diseases/n（%）	5 （10.87）
Etiology
Pneumonia/n（%）	24 （52.17）
CNS lesions/n（%）	16 （34.78）
Septic pyemia/n（%）	6 （13.04）
Complication
MODS/n（%）	6 （13.04）
Treatment
Glucocorticoid/n（%）	43 （93.50）
Parenteral nutrition/n（%）	7 （15.22）
Fasting/n（%）	10 （21.74）
Surgical interventions/n（%）	26 （56.52）
Prognosis
Weaning failure/n（%）	18 （39.13）
Mortality in PICU/n（%）	10 （21.74）
Duration of mechanical ventilation/d	8.00 （7.00， 12.00）
Hospitalization days in PICU/d	20.00 （11.00， 31.00）

Indicator	MV			H value	P value
Indicator	0 h	48 h	96 h	H value	P value
Oxygenation status
SaO₂/%	97.80 （95.2, 99.40）	97.00 （91.63, 99.23）	97.50 （89.80, 99.23）	0.73	0.70
OI/mmHg	349.55±166.03	305.97±159.04	321.24±161.00	0.90	0.41
PaCO₂/mmHg	42.32±8.60	44.44±10.85	43.23±8.37	0.60	0.55
Ventilator parameter
P_peak/cmH₂O	17.61±4.43	16.72±4.04	16.04±3.83	1.46	0.24
P_mean/cmH₂O	8.83±3.48	8.26±3.28	7.49±2.60	1.78	0.17
PEEP/cmH₂O	4.57±1.91	4.46±1.72	4.04±1.45	0.89	0.42
FiO₂/%	36.76±11.43	35.07±10.63	34.40±10.12	0.39	0.68
MVe/（L·min^-1）	3.38±1.83	3.21±1.64	3.03±1.48	0.42	0.66
TV/（mL·kg^-1）	7.54±3.31	7.44±2.89	7.04±2.85	2.50	0.09

Indicator	MV			H value	P value
Indicator	0 h	48 h	96 h	H value	P value
Oxygenation status
SaO₂/%	97.80 （95.2, 99.40）	97.00 （91.63, 99.23）	97.50 （89.80, 99.23）	0.73	0.70
OI/mmHg	349.55±166.03	305.97±159.04	321.24±161.00	0.90	0.41
PaCO₂/mmHg	42.32±8.60	44.44±10.85	43.23±8.37	0.60	0.55
Ventilator parameter
P_peak/cmH₂O	17.61±4.43	16.72±4.04	16.04±3.83	1.46	0.24
P_mean/cmH₂O	8.83±3.48	8.26±3.28	7.49±2.60	1.78	0.17
PEEP/cmH₂O	4.57±1.91	4.46±1.72	4.04±1.45	0.89	0.42
FiO₂/%	36.76±11.43	35.07±10.63	34.40±10.12	0.39	0.68
MVe/（L·min^-1）	3.38±1.83	3.21±1.64	3.03±1.48	0.42	0.66
TV/（mL·kg^-1）	7.54±3.31	7.44±2.89	7.04±2.85	2.50	0.09

Indicator	MV			H value	P value
Indicator	0 h	48 h	96 h	H value	P value
Thickness /cm	0.69 （0.56, 0.90）	0.74 （0.57, 0.89）	0.70 （0.56, 0.91）	1.06	0.59
Atrophy rate /%	0 （0, 0）	-1.30 （-8.80, 5.77）	0 （-6.92, 7.81）	1.06	0.59