Journal of Perinatology (2015), 1–4 © 2015 Nature America, Inc. All rights reserved 0743-8346/15 www.nature.com/jp
ORIGINAL ARTICLE
Prone positioning decreases cardiac output and increases systemic vascular resistance in neonates M Ma1,2,3, S Noori1,2,3, J-M Maarek4, DP Holschneider4,5, EH Rubinstein6 and I Seri1,2,3,7 OBJECTIVE: To evaluate the cardiovascular response to short-term prone positioning in neonates. STUDY DESIGN: In this prospective study, we continuously monitored heart rate (HR), stroke volume (SV) and cardiac output (CO) by electrical velocimetry in hemodynamically stable neonates in each of the following positions for 10 min: supine, prone and backto-supine position. Skin blood flow (SBF) was also continuously assessed on the forehead or foot using Laser Doppler technology. Systemic vascular resistance (SVR) index was calculated as mean blood pressure (BP)/CO. Data were analyzed using repeated measures analysis of variance. RESULTS: Thirty neonates (gestational age: 35 ± 4 weeks; postmenstrual age: 36 ± 3 weeks) were enrolled. HR did not change in response to positioning. However, in prone position, SV, CO and SBF decreased and SVR index increased from 1.5 ± 0.3 to 1.3 ± 0.3 ml kg − 1 (mean ± s.d., Po 0.01), 206 ± 44 to 180 ± 41 ml kg − 1 min − 1 (P o0.01), 0.54 ± 0.30 to 0.44 ± 0.29 perfusion units (P o 0.01) and 0.25 ± 0.06 to 0.30 ± 0.07 mm Hg ml − 1 kg − 1 min − 1 (P o0.01), respectively. After placing the infants back-to-supine position, SV, CO, SBF and SVR index returned to baseline. The above pattern of cardiovascular changes was consistent in vast majority of the studied neonates. CONCLUSIONS: Short-term prone positioning is associated with decreased SV, CO and SBF and increased calculated SVR index. Journal of Perinatology advance online publication, 15 January 2015; doi:10.1038/jp.2014.230
INTRODUCTION Prone positioning is a common practice in the neonatal intensive care unit. Prone positioning has been shown to improve oxygenation in extremely low-birth infants with chronic lung disease and in neonates with respiratory failure.1,2 Decreased gastric residual and improved feeding tolerance have also been observed when preterm infants are positioned prone after feeding.3 In addition, improved sleep state and decreased stress behaviors have been reported in neonates placed prone.4 On the other hand, prone positioning is also associated with some adverse effects. For example, decreased cerebral oxygenation has been reported in stable preterm and term neonates sleeping in a prone position.5,6 Furthermore, sleeping prone is a significant risk factor for sudden infant death syndrome. Prone positioning also has significant effects on the cardiovascular system in adults.7–12 Yet, to our knowledge, the impact of prone positioning on cardiac output (CO) and peripheral circulation in the neonatal population has not been studied. Therefore, in this study, we sought to investigate the cardiovascular effects of short-term prone positioning in hemodynamically stable neonates. On the basis of the adult studies, we hypothesized that prone positioning would be associated with a drop in CO and peripheral perfusion. METHODS This was a prospective study approved by the institutional review board at the Children’s Hospital Los Angeles and CHA-Hollywood Presbyterian Medical Center. Parental informed consent was obtained before the study.
We enrolled hemodynamically stable neonates who were admitted to the neonatal intensive care unit. We excluded neonates who had major congenital malformations were small for gestational age (birth weight o5th percentile) and/or were receiving mechanical ventilation. Thirty neonates were enrolled in the study. The reasons for initial admission were respiratory distress (n = 14), prematurity with gestational age o35 weeks (n = 9), hypoglycemia (n = 3) low birth weight ( o2250 g, n = 2) and feeding intolerance (n = 2). At the time of study, all the neonates were stable. After being fitted with the monitoring devices, we waited until the neonates became completely calm or fell asleep, while in supine position. After the data collection was completed in supine position, the subjects were placed in prone position and the data were collected again, followed by being repositioned back-to-supine position for the final data collection period. Each period lasted for 10 min. Heart rate, stroke volume (SV) and CO were monitored by electrical velocimetry (EV) using the ICON monitor (Cardiotronic, La Jolla, CA, USA). The EV monitoring system has been validated against invasive methods of CO measurements with good correlation in animals, children and adult humans.13–15 We also found that CO measured by EV is comparable to that assessed by echocardiography in neonates.16 The principle of EV is described elsewhere.16 In brief, four electrocardiographic electrodes are placed over the skin of the forehead, left side of the neck, left midaxillary line at the level of xiphoid process and left thigh. A small alternating electrical current flows through the patient from the outer electrocardiographic electrodes and the resulting voltage is measured by the inner electrodes. After appropriate filtering, the major contributing factor to conductance (1/impedance) of the current is blood flow in the ascending aorta. As the aortic valve opens during systole, red blood cells align owing to the forward flow of blood in the ascending aorta, resulting in an abrupt decrease of impedance. Conversely, with the near cessation of blood flow
1 Division of Neonatology and the Center for Fetal and Neonatal Medicine, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2The LAC+USC Medical Center, Los Angeles, CA, USA; 3Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 4Department of Biomedical Engineering, University of Southern California, Los Angeles, CA,USA; 5Department of Psychiatry and Behavioral Science, University of Southern California, Los Angeles, CA, USA; 6Department of Anesthesiology, University of California Los Angeles, Los Angeles, CA,USA and 7Sidra Neonatology Center of Excellence, Department of Pediatrics, Sidra Medical and Research Center, Doha, Qatar. Correspondence: Dr S Noori, Division of Neonatology and the Center for Fetal and Neonatal Medicine, Department of Pediatrics, Children’s Hospital Los Angeles, 4650 Sunset Boulevard, MS# 31, Los Angeles, CA 90027, USA. E-mail: [email protected] Received 28 August 2014; revised 9 November 2014; accepted 20 November 2014
Neonatal cardiovascular changes in prone M Ma et al
2 in the ascending aorta during diastole, red blood cells become misaligned, resulting in an increase in impedance. The change in impedance during the cardiac cycle serves as the basis of estimating CO.16 In this study, we set the monitor to output heart rate, SV and CO every 10 s. In each position, we first waited for 3 min for the subject to settle, then allowed for a 2-min stabilization period, followed by data collection for the last 5 min of the given positioning period. Data were averaged for the duration of the 5-min data collection. The skin blood flow (SBF) was continuously assessed on the forehead or foot using Laser Doppler technology (PeriFlux 5000, Ardmore, PA, USA). Laser Doppler measures local microcirculatory blood flow using a beam of low-intensity Laser light (780 nm) carried by a fiber-optic probe. The measuring depth of this Laser light is in the order of 0.5–1 mm. Light hitting moving blood cells undergoes a change in wavelength, whereas light hitting static objects is unchanged. The change of wavelength serves as the basis for the model that estimates microcirculatory blood flow. SBF is expressed in an arbitrary perfusion unit. Data of SBF were collected every 0.025 s by the Laser Doppler device. As Laser Doppler is very sensitive to motion, after the initial 5-min stabilization period, we averaged SBF data obtained over 1 min of complete rest only. Blood pressure (BP) was measured by the oscillometric technique after completion of data acquisition in each position to minimize the potential impact of cuff inflation on cardiovascular function and patient movement. Systemic vascular resistance (SVR) index was calculated as mean BP/CO.
Statistical analysis Data are presented as mean ± s.d. or median (interquartile range). One way repeated measures analysis of variance (ANOVA) was used to determine the statistical significance of changes in cardiovascular function. A P-valueo0.05 was considered statistically significant.
RESULTS Thirty neonates with stable cardiopulmonary status were enrolled in this study. Heart rate, SV, CO and SBF were collected in all of the 30 patients. Data on BP were collected and SVR index was calculated only in the last 21 patients enrolled. Neonates were initially studied while lying quietly supine, then in prone position, followed by turning them back-to-supine position. Each period lasted for 10 min. Clinical characteristics of the study population are shown in Table 1. HR did not change in response to change in position (138 ± 17 vs 138 ± 18 beats per minute, P = 0.9, Figure 1a). Twenty-six neonates (87%) had a decrease in SV and CO when placed in prone position. The mean decrease in SV was 13% for all patients in prone position (1.5 ± 0.3 vs 1.3 ± 0.3 ml kg − 1, P o0.01, Figure 1b). As heart rate did not change, CO also decreased in prone position (206 ± 44 vs 180 ± 41 ml kg − 1 min − 1, P o0.01, Figure 1c). In addition, SBF also decreased in neonates placed Table 1.
Clinical characteristics of the study population (n = 30)
Gestation age (weeks)a a
Birth weight (g) Male/female ratio Race Hispanic White Black Asian Cesarean section Apgar at 1 mina Apgar at 5 mina Day of lifea Post-menstrual age (weeks)a a
Median (interquartile range).
Journal of Perinatology (2015), 1 – 4
37 (34–39) 2760 (2240–3460) 1.3 (17/13) 83.3% 6.7% 6.7% 3.3% 50% 8 8 5 37.5
(25) (2) (2) (1) (15) (5–8) (8–9) (2–7) (35–39)
prone (0.54 ± 0.30 vs 0.44 ± 0.29 perfusion unit, P o0.01, Figure 2). When the neonates were placed back-to-supine position, SV, CO and SBF returned to baseline. Although there was no statistically significant change in BP in response to position change, a trend to an increase in the diastolic (41 ± 7 vs 45 ± 7 mm Hg, P = 0.054) and mean BP (54 ± 7 vs 57 ± 6 mm Hg, P = 0.059) was noted when neonates were placed from supine to prone position (Figure 3). The calculated SVR index increased when neonates were placed from supine to prone position (0.25 ± 0.06 vs 0.30 ± 0.07 mm Hgml − 1 kg − 1 min − 1, P o 0.01), and returned to baseline following repositioning to supine position (Figure 4). DISCUSSION The findings of our study indicate that short-term prone positioning in neonates is associated with a significant decrease in SV, CO and skin microcirculatory blood flow and an increase of the calculated SVR index. We speculate that as a result of the increase in the intrathoracic pressure in prone position, venous return decreases leading to a decrease in SV and, as HR did not change in CO as well.17 We speculate that the decrease in SBF along with the increased calculated SVR index might represent a compensatory response to the decrease in CO in prone position. The finding of a reduction in CO in prone in neonates is consistent with findings in adults placed prone for spine surgery.7 In addition, decreases in CO in prone position have also been described in healthy adults using transesophageal echocardiography,8 noninvasive cardiac monitoring9 and gated myocardial perfusion Single Photon Emission Computed Tomography.10 Indeed, a decreased end-diastolic volume in prone position has been demonstrated in adult patients, suggesting that a decreased preload is the cause of the drop in the CO.8,10 Furthermore, an increase of plasma norepinephrine concentration along with an increase in heart rate has also been reported in healthy adults placed prone, suggesting a compensatory increase in sympathetic activity in response to the decreased CO.11 Unlike in adults whose heart rate increases in prone position,10–12 there was no change in the heart rate in our patient population. There may be a number of reasons for the lack of change in the heart rate in neonates when placed prone. First, our study was conducted on neonates who were mostly asleep during the study, which might result in decreased sympathetic activity. Second, autonomic regulation of cardiac function is immature in neonates. Indeed, the sympathetic response to induced cardiovascular stress, such as decreased CO or BP, increases with advancing postnatal age.18 Thus, maturational differences in the function of the autonomic nervous system may, at least in part, explain why HR increases in adults, but not in neonates in response to prone positioning. Interestingly, studies on the effects of prone positioning on HR in infants during sleep have shown variable results. A slight increase in HR during prone sleep has been reported in preterm and low-birth weight infants19,20 and term infants at 2–3 months of age.21,22 However, keeping in line with our findings, term neonates at 2–4 weeks of age showed no significant change in HR when asleep in prone position.21 Whereas BP decreased in term infants at both 2–4 weeks and 2–3 months of age, only the 2- to 3month-old infants had an increase in HR.21 This finding lends further support to the notion that the cardiovascular response to prone positioning is developmentally regulated. It is well known that sleeping prone is a significant risk factor for sudden infant death syndrome. In this context, our finding of a decreased SV in prone position is intriguing. In adults, a decrease in SV triggers compensatory mechanisms, including an increase in the sympathetic tone. This leads to increases in HR and vascular tone in the nonvital organs thus compensating for the decrease in SV, while increasing perfusion pressure. Therefore, we speculate that neurologic and autonomic immaturity, decreased SV in prone © 2015 Nature America, Inc.
Neonatal cardiovascular changes in prone M Ma et al
3
a
b
150
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100
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2 1.5 1 0.5
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Figure 1. Box and whisker plots depicting changes in HR (a), SV (b) and CO (c) in response to position changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller and the dots represent the outliers. N = 30; CO, cardiac output; HR, heart rate; SV, stroke volume.
P < 0.01
100
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0 Supine
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Figure 2. Changes of SBF in response to position changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller and the dots represent the outliers. N = 30; SBF, skin blood flow.
position and the presence of a precipitating event that counteracts the compensatory increase in vascular tone, such as an overheated environment or viral infection, might result in cardiovascular compromise potentially contributing to the development of sudden infant death syndrome in infants. However, as our study was designed to only examine the cardiovascular effects of short-term prone positioning, further studies are needed to assess whether the decrease in SV in prone position persists and is indeed a predisposing contributory factor to sudden infant death syndrome in infants sleeping prone. Our study has several limitations. Although EV is comparable to echocardiography in estimating CO16 and both are considered to have acceptable accuracy and precision for noninvasive bedside tools CO, they both can have significant measurement errors. However, the fact that the majority of our study subjects © 2015 Nature America, Inc.
Prone
Back to supine
Figure 3. Changes of systolic (□), diastolic (▧) and mean (▨) blood pressure in response to changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller and the dots represent the outliers. N = 21; BP, blood pressure.
presented with a decrease in CO when placed prone, makes an erroneous estimate of CO a highly unlikely explanation for our findings. Furthermore, the simultaneous decrease in skin perfusion measured by a different technology (Laser Doppler) suggests that our observations of the changes in cardiovascular function were correct. Another limitation of our study is that the effect of prone positioning on thoracic bioimpedance is not known. However, as mentioned above, the SV and CO findings using EV fit with the SBF data obtained by Laser Doppler. Our study is also limited by the relatively small sample size. Yet, despite this limitation, we were able to demonstrate statistically significant changes in cardiac and vascular function. It is also important to emphasize that our findings apply only to the cardiovascular effects of short-term prone positioning. Finally, although we minimized the occurrence of motion artifacts by conducting the study while the patients Journal of Perinatology (2015), 1 – 4
Neonatal cardiovascular changes in prone M Ma et al SVR index (mmHg/ml/kg/min)
4 P < 0.01
0.5
P < 0.05
0.4 0.3 0.2 0.1 Supine
Prone
Back to supine
Figure 4. Changes of SVR index in response to position changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller. N = 21; SVR = systemic vascular resistance.
were at quite rest or asleep without apparent movements, we have to mention that the Laser Doppler technology is very sensitive to motion. In summary, we found a significant decrease in SV, CO and skin perfusion in neonates placed in prone position. These changes returned to baseline after placing the subjects back-to-supine position. We also found that systemic vascular tone increased with prone positioning as evidenced by the increase in calculated SVR index and a trend of an increase in BP. We speculate that the increase in systemic vascular tone is a compensatory response to the decrease in CO. Future studies using comprehensive cardiovascular monitoring and focusing on alterations in cerebral oxygenation, respiratory changes and sleep states along with longer periods of positioning will advance the understanding of hemodynamic changes in response to prone positioning. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS This study was, in part, supported by grant support from the National Heart, Lung and Blood Institute (1RO1HL103765-01).
REFERENCES 1 Balaguer A, Escribano J, Roqué I, Figuls M, Rivas-Fernandez M. Infant position in neonates receiving mechanical ventilation. Cochrane Database Syst Rev 2013; 3: CD003668. 2 McEvoy C, Mendoza ME, Bowling S, Hewlett V, Sardesai S, Durand M. Prone positioning decreases episodes of hypoxemia in extremely low birth weight infants (1000 grams or less) with chronic lung disease. J Pediatr 1997; 130: 305–309.
Journal of Perinatology (2015), 1 – 4
3 Chen SS, Tzeng YL, Gau BS, Kuo PC, Chen JY. Effects of prone and supine positioning on gastric residuals in preterm infants: a time series with cross-over study. Int J Nurs Stud 2013; 50: 1459–1467. 4 Chang YJ, Anderson GC, Lin CH. Effects of prone and supine positions on sleep state and stress responses in mechanically ventilated preterm infants during the first postnatal week. J Adv Nurs 2002; 40: 161–169. 5 Bembich S, Oretti C, Travan L, Clarici A, Massaccesi S, Demarini S. Effects of prone and supine position on cerebral blood flow in preterm infants. J Pediatr 2012; 160: 162–164. 6 Wong FY, Witcombe NB, Yiallourou SR, Yorkston S, Dymowski AR, Krishnan L et al. Cerebral oxygenation is depressed during sleep in healthy term infants when they sleep prone. Pediatrics 2011; 127: e558–e565. 7 Edgcombe H, Carter K, Yarrow S. Anaesthesia in the prone position. Br J Anaesth 2008; 100: 165–183. 8 Dharmavaram S, Jellish WS, Nockels RP, Shea J, Mehmood R, Ghanayem A et al. Effect of prone positioning systems on hemodynamic and cardiac function during lumbar spine surgery: an echocardiographic study. Spine (Phila Pa 1976) 2006; 31: 1388–1393. Discussion 1394. 9 Sudheer PS, Logan SW, Ateleanu B, Hall JE. Haemodynamic effects of the prone position: a comparison of propofol total intravenous and inhalation anaesthesia. Anaesthesia 2006; 61: 138–141. 10 Schaefer WM, Lipke CS, Kühl HP, Koch KC, Kaiser HJ, Reinartz P et al. Prone versus supine patient positioning during gated 99mTc-sestamibi SPECT: effect on left ventricular volumes, ejection fraction, and heart rate. J Nucl Med 2004; 45: 2016–2020. 11 Pump B, Talleruphuus U, Christensen NJ, Warberg J, Norsk P. Effects of supine, prone, and lateral positions on cardiovascular and renal variables in humans. Am J Physiol Regul Integr Comp Physiol 2002; 283: R174–R180. 12 Yap K, Campbell P, Cherk M, McGrath C, Kalff V. Effect of prone versus supine positioning on left ventricular ejection fraction (LVEF) and heart rate using ECG gated Tl-201 myocardial perfusion scans and gated cardiac blood pool scans. J Med Imaging Radiat Oncol 2012; 56: 525–531. 13 Osthaus WA, Huber D, Beck C, Winterhalter M, Boethig D, Wessel A et al. Comparison of electrical velocimetry and transpulmonary thermodilution for measuring cardiac output in piglets. Paediatr Anaesth 2007; 17: 749–755. 14 Norozi K, Beck C, Osthaus WA, Wille I, Wessel A, Bertram H. Electrical velocimetry for measuring cardiac output in children with congenital heart disease. Br J Anaesth 2008; 100: 88–94. 15 Zoremba N, Bickenbach J, Krauss B, Rossaint R, Kuhlen R, Schälte G. Comparison of electrical velocimetry and thermodilution techniques for the measurement of cardiac output. Acta Anaesthesiol Scand 2007; 51: 1314–1319. 16 Noori S, Drabu B, Soleymani S, Seri I. Continuous non-invasive cardiac output measurements in the neonate by electrical velocimetry: a comparison with echocardiography. Arch Dis Child Fetal Neonatal Ed 2012; 97: F340–F343. 17 Skatvedt O, Grøgaard J. Infant sleeping position and inspiratory pressures in the upper airways and oesophagus. Arch Dis Child 1994; 71: 138–140. 18 Yiallourou SR, Sands SA, Walker AM, Horne RS. Maturation of heart rate and blood pressure variability during sleep in term-born infants. Sleep 2012; 35: 177–186. 19 Sahni R, Schulze KF, Kashyap S, Ohira-Kist K, Fifer WP, Myers MM. Postural differences in cardiac dynamics during quiet and active sleep in low birthweight infants. Acta Paediatr 1999; 88: 1396–1401. 20 Ammari A, Schulze KF, Ohira-Kist K, Kashyap S, Fifer WP, Myers MM et al. Effects of body position on thermal, cardiorespiratory and metabolic activity in low birth weight infants. Early Hum Dev 2009; 85: 497–501. 21 Yiallourou SR, Walker AM, Horne RS. Effects of sleeping position on development of infant cardiovascular control. Arch Dis Child 2008; 93: 868–872. 22 Chong A, Murphy N, Matthews T. Effect of prone sleeping on circulatory control in infants. Arch Dis Child 2000; 82: 253–256.
© 2015 Nature America, Inc.
ORIGINAL ARTICLE
Prone positioning decreases cardiac output and increases systemic vascular resistance in neonates M Ma1,2,3, S Noori1,2,3, J-M Maarek4, DP Holschneider4,5, EH Rubinstein6 and I Seri1,2,3,7 OBJECTIVE: To evaluate the cardiovascular response to short-term prone positioning in neonates. STUDY DESIGN: In this prospective study, we continuously monitored heart rate (HR), stroke volume (SV) and cardiac output (CO) by electrical velocimetry in hemodynamically stable neonates in each of the following positions for 10 min: supine, prone and backto-supine position. Skin blood flow (SBF) was also continuously assessed on the forehead or foot using Laser Doppler technology. Systemic vascular resistance (SVR) index was calculated as mean blood pressure (BP)/CO. Data were analyzed using repeated measures analysis of variance. RESULTS: Thirty neonates (gestational age: 35 ± 4 weeks; postmenstrual age: 36 ± 3 weeks) were enrolled. HR did not change in response to positioning. However, in prone position, SV, CO and SBF decreased and SVR index increased from 1.5 ± 0.3 to 1.3 ± 0.3 ml kg − 1 (mean ± s.d., Po 0.01), 206 ± 44 to 180 ± 41 ml kg − 1 min − 1 (P o0.01), 0.54 ± 0.30 to 0.44 ± 0.29 perfusion units (P o 0.01) and 0.25 ± 0.06 to 0.30 ± 0.07 mm Hg ml − 1 kg − 1 min − 1 (P o0.01), respectively. After placing the infants back-to-supine position, SV, CO, SBF and SVR index returned to baseline. The above pattern of cardiovascular changes was consistent in vast majority of the studied neonates. CONCLUSIONS: Short-term prone positioning is associated with decreased SV, CO and SBF and increased calculated SVR index. Journal of Perinatology advance online publication, 15 January 2015; doi:10.1038/jp.2014.230
INTRODUCTION Prone positioning is a common practice in the neonatal intensive care unit. Prone positioning has been shown to improve oxygenation in extremely low-birth infants with chronic lung disease and in neonates with respiratory failure.1,2 Decreased gastric residual and improved feeding tolerance have also been observed when preterm infants are positioned prone after feeding.3 In addition, improved sleep state and decreased stress behaviors have been reported in neonates placed prone.4 On the other hand, prone positioning is also associated with some adverse effects. For example, decreased cerebral oxygenation has been reported in stable preterm and term neonates sleeping in a prone position.5,6 Furthermore, sleeping prone is a significant risk factor for sudden infant death syndrome. Prone positioning also has significant effects on the cardiovascular system in adults.7–12 Yet, to our knowledge, the impact of prone positioning on cardiac output (CO) and peripheral circulation in the neonatal population has not been studied. Therefore, in this study, we sought to investigate the cardiovascular effects of short-term prone positioning in hemodynamically stable neonates. On the basis of the adult studies, we hypothesized that prone positioning would be associated with a drop in CO and peripheral perfusion. METHODS This was a prospective study approved by the institutional review board at the Children’s Hospital Los Angeles and CHA-Hollywood Presbyterian Medical Center. Parental informed consent was obtained before the study.
We enrolled hemodynamically stable neonates who were admitted to the neonatal intensive care unit. We excluded neonates who had major congenital malformations were small for gestational age (birth weight o5th percentile) and/or were receiving mechanical ventilation. Thirty neonates were enrolled in the study. The reasons for initial admission were respiratory distress (n = 14), prematurity with gestational age o35 weeks (n = 9), hypoglycemia (n = 3) low birth weight ( o2250 g, n = 2) and feeding intolerance (n = 2). At the time of study, all the neonates were stable. After being fitted with the monitoring devices, we waited until the neonates became completely calm or fell asleep, while in supine position. After the data collection was completed in supine position, the subjects were placed in prone position and the data were collected again, followed by being repositioned back-to-supine position for the final data collection period. Each period lasted for 10 min. Heart rate, stroke volume (SV) and CO were monitored by electrical velocimetry (EV) using the ICON monitor (Cardiotronic, La Jolla, CA, USA). The EV monitoring system has been validated against invasive methods of CO measurements with good correlation in animals, children and adult humans.13–15 We also found that CO measured by EV is comparable to that assessed by echocardiography in neonates.16 The principle of EV is described elsewhere.16 In brief, four electrocardiographic electrodes are placed over the skin of the forehead, left side of the neck, left midaxillary line at the level of xiphoid process and left thigh. A small alternating electrical current flows through the patient from the outer electrocardiographic electrodes and the resulting voltage is measured by the inner electrodes. After appropriate filtering, the major contributing factor to conductance (1/impedance) of the current is blood flow in the ascending aorta. As the aortic valve opens during systole, red blood cells align owing to the forward flow of blood in the ascending aorta, resulting in an abrupt decrease of impedance. Conversely, with the near cessation of blood flow
1 Division of Neonatology and the Center for Fetal and Neonatal Medicine, Department of Pediatrics, Children’s Hospital Los Angeles, Los Angeles, CA, USA; 2The LAC+USC Medical Center, Los Angeles, CA, USA; 3Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; 4Department of Biomedical Engineering, University of Southern California, Los Angeles, CA,USA; 5Department of Psychiatry and Behavioral Science, University of Southern California, Los Angeles, CA, USA; 6Department of Anesthesiology, University of California Los Angeles, Los Angeles, CA,USA and 7Sidra Neonatology Center of Excellence, Department of Pediatrics, Sidra Medical and Research Center, Doha, Qatar. Correspondence: Dr S Noori, Division of Neonatology and the Center for Fetal and Neonatal Medicine, Department of Pediatrics, Children’s Hospital Los Angeles, 4650 Sunset Boulevard, MS# 31, Los Angeles, CA 90027, USA. E-mail: [email protected] Received 28 August 2014; revised 9 November 2014; accepted 20 November 2014
Neonatal cardiovascular changes in prone M Ma et al
2 in the ascending aorta during diastole, red blood cells become misaligned, resulting in an increase in impedance. The change in impedance during the cardiac cycle serves as the basis of estimating CO.16 In this study, we set the monitor to output heart rate, SV and CO every 10 s. In each position, we first waited for 3 min for the subject to settle, then allowed for a 2-min stabilization period, followed by data collection for the last 5 min of the given positioning period. Data were averaged for the duration of the 5-min data collection. The skin blood flow (SBF) was continuously assessed on the forehead or foot using Laser Doppler technology (PeriFlux 5000, Ardmore, PA, USA). Laser Doppler measures local microcirculatory blood flow using a beam of low-intensity Laser light (780 nm) carried by a fiber-optic probe. The measuring depth of this Laser light is in the order of 0.5–1 mm. Light hitting moving blood cells undergoes a change in wavelength, whereas light hitting static objects is unchanged. The change of wavelength serves as the basis for the model that estimates microcirculatory blood flow. SBF is expressed in an arbitrary perfusion unit. Data of SBF were collected every 0.025 s by the Laser Doppler device. As Laser Doppler is very sensitive to motion, after the initial 5-min stabilization period, we averaged SBF data obtained over 1 min of complete rest only. Blood pressure (BP) was measured by the oscillometric technique after completion of data acquisition in each position to minimize the potential impact of cuff inflation on cardiovascular function and patient movement. Systemic vascular resistance (SVR) index was calculated as mean BP/CO.
Statistical analysis Data are presented as mean ± s.d. or median (interquartile range). One way repeated measures analysis of variance (ANOVA) was used to determine the statistical significance of changes in cardiovascular function. A P-valueo0.05 was considered statistically significant.
RESULTS Thirty neonates with stable cardiopulmonary status were enrolled in this study. Heart rate, SV, CO and SBF were collected in all of the 30 patients. Data on BP were collected and SVR index was calculated only in the last 21 patients enrolled. Neonates were initially studied while lying quietly supine, then in prone position, followed by turning them back-to-supine position. Each period lasted for 10 min. Clinical characteristics of the study population are shown in Table 1. HR did not change in response to change in position (138 ± 17 vs 138 ± 18 beats per minute, P = 0.9, Figure 1a). Twenty-six neonates (87%) had a decrease in SV and CO when placed in prone position. The mean decrease in SV was 13% for all patients in prone position (1.5 ± 0.3 vs 1.3 ± 0.3 ml kg − 1, P o0.01, Figure 1b). As heart rate did not change, CO also decreased in prone position (206 ± 44 vs 180 ± 41 ml kg − 1 min − 1, P o0.01, Figure 1c). In addition, SBF also decreased in neonates placed Table 1.
Clinical characteristics of the study population (n = 30)
Gestation age (weeks)a a
Birth weight (g) Male/female ratio Race Hispanic White Black Asian Cesarean section Apgar at 1 mina Apgar at 5 mina Day of lifea Post-menstrual age (weeks)a a
Median (interquartile range).
Journal of Perinatology (2015), 1 – 4
37 (34–39) 2760 (2240–3460) 1.3 (17/13) 83.3% 6.7% 6.7% 3.3% 50% 8 8 5 37.5
(25) (2) (2) (1) (15) (5–8) (8–9) (2–7) (35–39)
prone (0.54 ± 0.30 vs 0.44 ± 0.29 perfusion unit, P o0.01, Figure 2). When the neonates were placed back-to-supine position, SV, CO and SBF returned to baseline. Although there was no statistically significant change in BP in response to position change, a trend to an increase in the diastolic (41 ± 7 vs 45 ± 7 mm Hg, P = 0.054) and mean BP (54 ± 7 vs 57 ± 6 mm Hg, P = 0.059) was noted when neonates were placed from supine to prone position (Figure 3). The calculated SVR index increased when neonates were placed from supine to prone position (0.25 ± 0.06 vs 0.30 ± 0.07 mm Hgml − 1 kg − 1 min − 1, P o 0.01), and returned to baseline following repositioning to supine position (Figure 4). DISCUSSION The findings of our study indicate that short-term prone positioning in neonates is associated with a significant decrease in SV, CO and skin microcirculatory blood flow and an increase of the calculated SVR index. We speculate that as a result of the increase in the intrathoracic pressure in prone position, venous return decreases leading to a decrease in SV and, as HR did not change in CO as well.17 We speculate that the decrease in SBF along with the increased calculated SVR index might represent a compensatory response to the decrease in CO in prone position. The finding of a reduction in CO in prone in neonates is consistent with findings in adults placed prone for spine surgery.7 In addition, decreases in CO in prone position have also been described in healthy adults using transesophageal echocardiography,8 noninvasive cardiac monitoring9 and gated myocardial perfusion Single Photon Emission Computed Tomography.10 Indeed, a decreased end-diastolic volume in prone position has been demonstrated in adult patients, suggesting that a decreased preload is the cause of the drop in the CO.8,10 Furthermore, an increase of plasma norepinephrine concentration along with an increase in heart rate has also been reported in healthy adults placed prone, suggesting a compensatory increase in sympathetic activity in response to the decreased CO.11 Unlike in adults whose heart rate increases in prone position,10–12 there was no change in the heart rate in our patient population. There may be a number of reasons for the lack of change in the heart rate in neonates when placed prone. First, our study was conducted on neonates who were mostly asleep during the study, which might result in decreased sympathetic activity. Second, autonomic regulation of cardiac function is immature in neonates. Indeed, the sympathetic response to induced cardiovascular stress, such as decreased CO or BP, increases with advancing postnatal age.18 Thus, maturational differences in the function of the autonomic nervous system may, at least in part, explain why HR increases in adults, but not in neonates in response to prone positioning. Interestingly, studies on the effects of prone positioning on HR in infants during sleep have shown variable results. A slight increase in HR during prone sleep has been reported in preterm and low-birth weight infants19,20 and term infants at 2–3 months of age.21,22 However, keeping in line with our findings, term neonates at 2–4 weeks of age showed no significant change in HR when asleep in prone position.21 Whereas BP decreased in term infants at both 2–4 weeks and 2–3 months of age, only the 2- to 3month-old infants had an increase in HR.21 This finding lends further support to the notion that the cardiovascular response to prone positioning is developmentally regulated. It is well known that sleeping prone is a significant risk factor for sudden infant death syndrome. In this context, our finding of a decreased SV in prone position is intriguing. In adults, a decrease in SV triggers compensatory mechanisms, including an increase in the sympathetic tone. This leads to increases in HR and vascular tone in the nonvital organs thus compensating for the decrease in SV, while increasing perfusion pressure. Therefore, we speculate that neurologic and autonomic immaturity, decreased SV in prone © 2015 Nature America, Inc.
Neonatal cardiovascular changes in prone M Ma et al
3
a
b
150
SV (ml/kg)
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P < 0.01
2.5
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2 1.5 1 0.5
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c P < 0.01
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300
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250 200 150 100 Supine
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Figure 1. Box and whisker plots depicting changes in HR (a), SV (b) and CO (c) in response to position changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller and the dots represent the outliers. N = 30; CO, cardiac output; HR, heart rate; SV, stroke volume.
P < 0.01
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P = 0.057 BP (mmHg)
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1
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P = 0.059 P = 0.054
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0 Supine
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Figure 2. Changes of SBF in response to position changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller and the dots represent the outliers. N = 30; SBF, skin blood flow.
position and the presence of a precipitating event that counteracts the compensatory increase in vascular tone, such as an overheated environment or viral infection, might result in cardiovascular compromise potentially contributing to the development of sudden infant death syndrome in infants. However, as our study was designed to only examine the cardiovascular effects of short-term prone positioning, further studies are needed to assess whether the decrease in SV in prone position persists and is indeed a predisposing contributory factor to sudden infant death syndrome in infants sleeping prone. Our study has several limitations. Although EV is comparable to echocardiography in estimating CO16 and both are considered to have acceptable accuracy and precision for noninvasive bedside tools CO, they both can have significant measurement errors. However, the fact that the majority of our study subjects © 2015 Nature America, Inc.
Prone
Back to supine
Figure 3. Changes of systolic (□), diastolic (▧) and mean (▨) blood pressure in response to changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller and the dots represent the outliers. N = 21; BP, blood pressure.
presented with a decrease in CO when placed prone, makes an erroneous estimate of CO a highly unlikely explanation for our findings. Furthermore, the simultaneous decrease in skin perfusion measured by a different technology (Laser Doppler) suggests that our observations of the changes in cardiovascular function were correct. Another limitation of our study is that the effect of prone positioning on thoracic bioimpedance is not known. However, as mentioned above, the SV and CO findings using EV fit with the SBF data obtained by Laser Doppler. Our study is also limited by the relatively small sample size. Yet, despite this limitation, we were able to demonstrate statistically significant changes in cardiac and vascular function. It is also important to emphasize that our findings apply only to the cardiovascular effects of short-term prone positioning. Finally, although we minimized the occurrence of motion artifacts by conducting the study while the patients Journal of Perinatology (2015), 1 – 4
Neonatal cardiovascular changes in prone M Ma et al SVR index (mmHg/ml/kg/min)
4 P < 0.01
0.5
P < 0.05
0.4 0.3 0.2 0.1 Supine
Prone
Back to supine
Figure 4. Changes of SVR index in response to position changes from supine (white) to prone (dark gray) and back to the supine position (light gray). The box represents the interquartile range (IQR), the horizontal line in the box is the median, the bars are the IQR × 1.5 or maximum/minimum values whichever smaller. N = 21; SVR = systemic vascular resistance.
were at quite rest or asleep without apparent movements, we have to mention that the Laser Doppler technology is very sensitive to motion. In summary, we found a significant decrease in SV, CO and skin perfusion in neonates placed in prone position. These changes returned to baseline after placing the subjects back-to-supine position. We also found that systemic vascular tone increased with prone positioning as evidenced by the increase in calculated SVR index and a trend of an increase in BP. We speculate that the increase in systemic vascular tone is a compensatory response to the decrease in CO. Future studies using comprehensive cardiovascular monitoring and focusing on alterations in cerebral oxygenation, respiratory changes and sleep states along with longer periods of positioning will advance the understanding of hemodynamic changes in response to prone positioning. CONFLICT OF INTEREST The authors declare no conflict of interest.
ACKNOWLEDGEMENTS This study was, in part, supported by grant support from the National Heart, Lung and Blood Institute (1RO1HL103765-01).
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