Journal of Pediatric Surgery xxx (2015) xxx–xxx
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Effects of ventilation modalities on near-infrared spectroscopy in surgically corrected CDH infants☆ Andrea Conforti ⁎,1, Paola Giliberti 1, Francesca Landolfo, Laura Valfrè, Claudia Columbo, Vito Mondi, Irma Capolupo, Andrea Dotta, Pietro Bagolan Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, Rome, Italy
a r t i c l e
i n f o
Article history: Received 16 October 2014 Received in revised form 25 July 2015 Accepted 31 July 2015 Available online xxxx Key words: Congenital diaphragmatic hernia NIRS conventional mechanical ventilation high-frequency oscillatory ventilation CMV HFOV
a b s t r a c t Background: Near-infrared spectroscopy (NIRS) is a noninvasive technique for monitoring tissue oxygenation and perfusion. The aim of this study was to evaluate cerebral and splanchnic NIRS changes in CDH operated infants enrolled into the VICI trial and therefore randomized for ventilatory modalities. Materials and methods: CDH newborns enrolled into the VICI trial (Netherlands Trial Register, NTR 1310) were randomized at birth for high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) according to the trial. Cerebral oxygenation (rSO2C) and splanchnic oxygenation (rSO2S) were obtained by NIRS (INVOS 5100; Somanetics, Troy, MI) before and after surgery. Variations in rSO2C and rSO2S were evaluated. Mann–Whitney test and one-way ANOVA were used as appropriate. p b 0.05 was considered significant. Results: Thirteen VICI trial patients underwent surgical repair between March 2011 and December 2012, and were enrolled in the study. Seven patients were assigned to HFOV and six to CMV group respectively. During surgery, a significant reduction in rSO2C (p = 0.0001) and rSO2S (p = 0.005) were observed. HFOV patients experienced prolonged reduction in rSO2C value (p = 0.003) while rSO2S did not vary between HFOV and CMV (p = 0.94). Conclusions: Surgical CDH repair was associated with decrease of cerebral and splanchnic oxygenation, regardless of ventilation. Patients ventilated by HFOV need a longer time interval to recovery normal rSO2C values, than those ventilated by CMV. This may be owing to a different impact of HFOV on patients' hemodynamic status with a higher impairment on total venous return and its negative consequences on cardiac output. © 2015 Elsevier Inc. All rights reserved.
Congenital diaphragmatic hernia (CDH) is a severe congenital anomaly of the diaphragm resulting in pulmonary hypoplasia and pulmonary hypertension. It is associated with a high risk of mortality and pulmonary morbidity. Previous retrospective studies have reported high-frequency oscillatory ventilation (HFOV) to reduce pulmonary morbidity in infants with CDH, while others indicated HFOV to be associated with worse outcome. To solve this issue, in 2011 the CDH-EURO Consortium started a multicenter randomized controlled trial (the VICI trial) to compare initial ventilatory treatment with HFOV and conventional mechanical ventilation (CMV) in infants with CDH [1]. The primary objective of this trial is to determine if there is a difference in the incidence of bronchopulmonary dysplasia and/or death within the first 28 days of life between newborns with congenital diaphragmatic hernia treated with HFOV and those treated with CMV as initial ventilation mode. Secondarily, the trial aims to compare the severity of chronic
lung disease, ventilator-induced lung injury and pulmonary hypertension by using clinical and laboratory parameters. Near-infrared spectroscopy (NIRS) is a noninvasive technique aimed to monitor cerebral oxygenation and hemodynamics in humans. In recent years NIRS has become a valuable tool to guide intraoperative anesthesia during cardiac surgery, in adults as well as in children [2]. Pediatric experiences have been also reported in studies focused on neuroprotection in preterm infants [3,4]. However, few reports are available on the effectiveness of NIRS monitoring in major surgery for noncardiac abnormalities, particularly in newborns patients [5]. The aim of the present study is to investigate NIRS changes in infants treated for high risk CDH and enrolled in the VICI trial (Netherlands Trial Register, NTR 1310).
1. Materials and methods
☆ None of the authors have any conflict of interest. ⁎ Corresponding author at: Department of Medical and Surgical Neonatology, Bambino Gesù Children's Hospital, 4, Piazza S.Onofrio, 00165, Rome, Italy. Tel.: +39 06 6859 2523; fax: +39 06 6859 2513. E-mail address:
[email protected] (A. Conforti). 1 PG and AC have to be considered first co-authors.
All patients treated, between March 2011 and December 2012, for high risk CDH at the Bambino Gesù Children's Hospital and randomized for the VICI trial, were enrolled into the study. High risk CDH was defined, according to literature [6], as prenatal diagnosis and/or developing respiratory symptoms within 6-hour after birth. The VICI trial oversight permission was obtained before undertaking the study. The
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Please cite this article as: Conforti A, et al, Effects of ventilation modalities on near-infrared spectroscopy in surgically corrected CDH infants, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.07.021
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A. Conforti et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx
results of our study do not interfere with the VICI trial guidelines and could rather contribute with new interesting data. This is a prospective observational cohort study, and institutional review board approved the study waiving the need for informed consent because of the observational nature of the study. All patients were screened for major associated abnormalities and for renal function. Preoperative assessment included cerebral, cardiac and renal ultrasound and renal functional tests (creatinine level and blood urea nitrogen). 1.1. VICI trial randomization A central, block randomization stratified per center was carried out at the Erasmus MC, Rotterdam, to achieve equal distribution of the two ventilation modalities among the participant centers. 1.2. Near-infrared spectroscopy A near-infrared spectrometer (INVOS; Somanetics, Troy, MI), equipped with two independent emittent-sensor pairs, was used for simultaneous measurement of cerebral oxygenation (rSO2C) and splanchnic oxygenation (rSO2S) via cerebral and splanchnic sensor applied to the forehead and renal region, respectively (Fig. 1). The main purpose of NIRS is to evaluate tissue perfusion and oxygenation continuously and noninvasively. The combined properties of absorption and dispersion of the near infrared energy determine the diffused reflection of the infrared light, which contains information on the chemical composition of the compound. Therefore, with NIRS the tissue oxygenation index or the regional saturation can be continuously monitored, providing “live” information on tissue oxygenation and perfusion [5]. NIRS monitoring started at patient's arrival in the neonatal intensive care unit. Measurements were recorded (at least) up to 48 hours after surgery. A significant decrement in NIRS value was defined as variation of more than 20% from basal value. Each patient has different basal value
for rSO2C and rSO2S according to the well-known significant variability in NIRS measurement temporally and between individual patients [7]. Corporeal temperature, arterial pH, blood pressure, transcutaneous O2 (PaO2) and CO2 (PaCO2) saturation and urine output value, were recorded during all the study period and throughout NIRS registration. 1.3. Ventilation After birth, all infants were immediately intubated. In general, our goals are to achieve preductal saturations between 85 and 95%, postductal saturation levels above 70% and arterial CO2 levels between 45 and 60 mm Hg (permissive hypercapnia). Conventional mechanical ventilation is provided by a neonatal ventilator capable of positive pressure ventilation or triggered modes (Babylog ventilator; Dräger Medical, Germany). HFOV is provided by a high-frequency oscillatory ventilator (Sensormedics 3100A/B HFO Ventilator; Viasys Healthcare, CareFusion, Yorba Linda, CA). If the allocated treatment is CMV, the following settings are used: a peak inspiratory pressure of 20–25 cm H2O, a positive end-expiratory pressure of 2–5 cm H2O and a frequency of 40–60 per minute. In case of HFOV, the settings are: a mean airway pressure of 13–17 cm H2O, a frequency of 10 Hz, an amplitude (Δp, cm H2O) of 30–50 obtaining chest vibrations, and an inspiration/expiration rate (I:E) of 1:1 [1]. 1.4. Surgery Surgical repair of diaphragmatic defect was performed after a period of, at least, 48 hours of clinical stabilization. Stability was defined according to the standardize postnatal treatment guidelines proposed by the European task force for CDH (CDH EURO Consortium) [1,8]. Surgical correction was performed, in all cases, through a left-sided subcostal abdominal incision, and a primary repair was accomplished with 6–8 interrupted nonabsorbable polyester sutures (2/0 Ethibond Excel TM; Ethicon, INC.2012). A polyethylene terephthalate patch
Fig. 1. A, An example of two-site INVOS 5100 rSO2 monitoring. B, The NIRS probe is applied on the skin over the forehead. C, Graphic reconstruction displayed in real time on the screen, shows variations in rSO2C and rSO2S; a significant fluctuation is defined as a variation N20% from baseline. Each dot on x-axis represents an hour. Operative time is indicated between arrows. Modified from: Conforti A, Giliberti P, Mondi V, et al. Near infrared spectroscopy: experience on esophageal atresia infants. J Pediatr Surg 2014; 49: 1064–1068.
Please cite this article as: Conforti A, et al, Effects of ventilation modalities on near-infrared spectroscopy in surgically corrected CDH infants, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.07.021
A. Conforti et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx
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Fig. 2. CONSORT diagram. CDH: congenital diaphragmatic hernia; NIRS: near-infrared spectroscopy, HFOV: high-frequency oscillatory ventilation; CMV: conventional mechanical ventilation.
(Dacron) was used if needed. All procedures were performed in the neonatal intensive care unit by experienced consultants. 1.5. Fluid and hemodynamic management All patients received restrictive fluid management in the first 24 h (40 ml/kg/d of fluids, including medication, with additional saline fluid therapy for intravascular filling). Thereafter, fluid and caloric intake should be increased based on clinical condition. Glucose, lipids and proteins should be given according the ESPGHAN/ESPEN guidelines [9]. Diuretics should be given in case of a positive fluid balance, aiming for diuresis of 1–2 ml/kg/h [1,8]. Hemodynamic management should be aimed at achieving appropriate end-organ perfusion determined by heart rate, capillary refill, urine output and lactate levels. If the heart rate is within the normal range, capillary refill is less than 3 s, urine output is more than 1.0 ml/kg/h, lactate concentration is less than 3 mmol/l and there are no symptoms of poor perfusion, no inotropic support is required [8]. If there are signs of poor perfusion or if the blood pressure is below the normal level for gestational age with a preductal saturation less than 80%, echocardiography should be performed to determine whether the poor perfusion is owing to hypovolemic or cardiogenic shock. If there is hypovolemia, saline fluid therapy should be started (10–20 ml/kg NaCl 0.9% up to 3 times during the first 1–2 h). If necessary, this should be followed by inotropic therapy. Hydrocortisone may be used for treatment of hypotension after conventional treatment has failed. In case of poor perfusion, vasopressor therapy should be started. In case of cardiogenic shock, as demonstrated by dysfunction of the left and/or right ventricle, inotropic agents should be considered [8]. 1.6. Data acquisition and statistical analysis NIRS values were continuously recorded at the forehead and renal region starting at patient's arrival in the NICU throughout 48 hours postoperation. Blood samples (0.3 mL each) were obtained to monitor blood gas value, oxygen saturation, hemoglobin level, as for VICI trial standard treatment protocol. Statistical analysis was performed using Mann–Whitney test and 1way ANOVA (Kruskal–Wallis and Dunn's multiple comparison tests) as appropriate. p b 0.05 was considered significant. Data are presented as medians and interquartile ranges (IQR).
2. Results Since the start of the VICI trial in 2009, we treated 79 infants affected by high risk CDH with an overall survival rate of 72% (57 patients survived). Between March 2011 (when the VICI trial started at our institution) and December 2012, we treated 35 patients, 20 of which (57%) were enrolled into the trial. According to the aim of the present study, we selected only those patients whose parents agreed to participate to the VICI trial in order to reduce variability within the groups considered. Therefore, 14 patients were available for the present analysis, since 6 patients died (30%) before surgery and no data on NIRS variations were then available. No postoperative deaths were observed (Fig. 2). Thirteen out of 14 patients were prospectively monitored with cerebral and splanchnic NIRS probes to assess changes before and after surgery, and to evaluate any differences on postoperative recover related to ventilator modalities. In one patient NIRS evaluation was not performed owing to technical problems. According to VICI trial, patients were randomly and centrally assigned to HFOV or CMV to achieve equal distribution of the two ventilation modalities among the participant centers. Therefore, 7 of our patients were enrolled into the HFOV group, while 6 into the CMV set. Table 1 Demographic and surgical characteristics of the patients enrolled into the study.
GA (wk); median (IQR) BW (g); median (IQR) Left side (%) Gender Prenatal diagnosis rate (%) LHR; median (IQR) LHR O/E; median (IQR) Age of surgery (h); median (IQR) Operative time; median (IQR) Liver up (%) Patch (%) Deaths (postsurgery)
Total 13
HFOV 7
CMV 6
p value
38 (35–40)
38 (36–40)
38 (35–39)
1
3055 (2660–3620) 13 (100%) 5 M; 8 F 13 (100)
3055 (2900–3620) 7 (100) 3 M; 4 F 7 (100)
3115 (2660–3480) 6 (100) 2 M; 4 F 6 (100)
1 1 1 1
1.8 (1.57-2.12) 55 (35–77) 72 (48–216)
1,8 (1.47-2.22) 56 (35–77) 120 (72–216)
1.9 (1.65-2.15) 55 (43–56) 60 (48–72)
0.75 1 0.008
73 (65–113)
73 (60–141)
76.5 (68.5–123)
0.88
5 (38) 3 (23) 0
4 (57) 3 (42) 0
1 (16) 0 0
0.27 0.19 -
GA: gestational age; BW: birth weight; LHR: lung to head ratio; IQR: interquartile range.
Please cite this article as: Conforti A, et al, Effects of ventilation modalities on near-infrared spectroscopy in surgically corrected CDH infants, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.07.021
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A. Conforti et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx
Table 2 Blood gas values after preoperative stabilization, during surgery and 48-hours after surgery.
pH at stabilization; median (IQR) PaO2 at stabilization, Torr; median (IQR) PaCO2 at stabilization, Torr; median (IQR) pH during surgery; median (IQR) PaO2 during surgery, Torr; median (IQR) PaCO2 during surgery, Torr; median (IQR) pH 48 h after surgery; median (IQR) PaO2 48 h after surgery, Torr; median (IQR) PaCO2 48 h after surgery, Torr; median (IQR)
Total
HFOV
CMV
p
7.40 (7.32–7.40) 78 (65–90.5) 37 (28.75–41.75) 7.32 (7.3–7.36) 74 (62.0–90.0) 43.5 (35.25–48.5) 7.39 (7.36–7.40) 74 (58.5–92.0) 37.5 (33.25–40)
7.36 (7.31–7.40) 79 (60.0–94.0) 40 (31–45.75) 7.32 (7.28–7.37) 74 (50.0–90.0) 46.5 (39.75–50) 7.38 (7.34–7.41) 67.0 (57.0–79.0) 38 (31.5–49.25)
7.40 (7.36–7.48) 75.5 (68.5–86.7) 36 (25.75–39) 7.33 (7.30–7.36) 73.5 (63.5–91.7) 42.5 (30–44.75) 7.39 (7.38–7.40) 76.5 (69.2–89) 37.5 (32–40)
0.32 0.94 0.33 0.8 0.94 0.17 0.32 0.25 0.68
IQR: interquartile range.
We do not observed any significant differences within the two groups concerning prenatal predictive risk factors, demographic characteristics and surgical features. Table 1 summarized demographic and surgical characteristics of the patients enrolled. Table 2 report blood gas exams at stabilization, at surgery, and 48 hours after surgery. Preductal and postductal saturation were similar for both groups, with no evidence of significant preductal and postductal differences (median preductal saturation: HFOV 95 (IQR 88–97) vs CMV 96 (90–98), p = 1; median postductal saturation: HFOV 95 (IQR 86–97) vs CMV 95 (84–99), p = 1). 2.1. Surgical intervention Surgical intervention was performed at a mean age of 72 hours, ranging from 48 to 216 hours; surprisingly statistical difference between HFOV and CMV groups [HFOV 120 hours (IQR 72–216) vs. CMV 60 hours (IQR 48–72), p = 0.008] was observed. Mean duration of the surgical procedure was 73 minutes, ranging from 65 to 113 minutes. In 3 cases, a Dacron (Dacron Bard De Bakey, Tempe, AZ) diaphragmatic patch was positioned. The subcostal laparotomy was primarily closed in all cases (Table 1). 2.2. NIRS monitoring NIRS evaluations were continuously recorded. Surgery determined a significant reduction of both cerebral and splanchnic NIRS values in most of the patients, independently on the ventilatory modalities. Noteworthy, we observed that the reductions in rSO2C and rSO2S started during surgery and persistently continue after the operations (Table 3). Median (and IQR) rSO2C and rSO2S percentage decreased for HFOV group 22% (IQR 20–33%) and for CMV group 16.5% (IQR 0–32.75%) with no statistically significant difference between the two groups (p = 0.35). The persistence of low NIRS values was significantly longer in those patients treated with HFO in comparison with CMV. Recovery of low NIRS values was observed at a mean time of almost 50 hours for rSO2C in HFOV group, in comparison with less than an hour in the CMV group (HFOV: 2977 min IQR 970–3084, vs 39.5 min IQR 0–103.8, p = 0.003). Concerning rSO2S similar durations were observed in the two groups (HFOV: 446.0 min IQR 0–748, vs CMV: 326.5 min IQR 0–814, p = 0.94) (Table 4). The analysis of those patients with liver herniated in the chest (4 patients in HFOV group) vs those patients with “liver down”, although confirming in both groups a significant variation in rSO2C values before
and after surgery, did not reveal any difference in terms of persistence of rSO2C reduction (“liver up” infants: 1740 min, IQR 540–6120 vs 278.5 min, IQR 0–2564; p = 0.29). 3. Discussion The present study confirms our previous finding indicating that infants with isolated severe CDH, treated with a delayed surgery, experience a statistically significant reduction in rSO2C during surgical repair of diaphragmatic defect [10]. Those findings are concordant with previous reports of surgical related decrement of cerebral and splanchnic NIRS monitoring during correction of major noncardiac abnormalities [5,11,12]. In particular, in all infants the most important modifications in cerebral hemodynamics were observed when the herniated viscera were repositioned into the abdomen. The reasons for these changes are not completely clear. One possible factor affecting cerebral circulation is PaCO2 [13]: hypocapnia induces a vasoconstricting response, whereas hypercapnia is followed by cerebral vasodilation [14]. Our infants were mechanically ventilated since birth, according to the Euro-Consortium guidelines, to maintain their arterial CO2 levels between 45 and 60 mm Hg. Furthermore, ventilatory settings were maintained constant during surgery avoiding sudden changes in transmural pulmonary pressure and arterial blood gases. The PaCO2 was continuously recorded by transcutaneous monitoring and by arterial blood gas analysis at the beginning and at the end of surgery, showing only a modest and insignificant rise. Therefore, it is unlikely that the observed changes in cerebral hemodynamics were caused by modifications of the PaCO2. Our data indicate that the most significant changes were observed during the repositioning of the herniated viscera into the abdomen; therefore, it is more likely that this maneuver might have interfered with cerebral perfusion, through a compression of the inferior vena cava and a reduction of the cardiac venous return [10]. These factors, along with the well known reduced autoregulation of cerebral blood flow, typical of the neonatal period, could have led to a decrease in cerebral perfusion. Apparently contradicting these findings, the presence of liver herniation in the chest did not represent risk factors for prolonged rSO2C reduction in our patients. However, this finding could be owing to the low number of patients enrolled into the study. Furthermore we found that rSO2S decreases during surgical correction of CDH. As observed for cerebral hemodynamic changes, also the major variations in splanchnic hemodynamics were observed during the repositioning of the herniated viscera into the abdomen. We
Table 3 Modification of rSO2C and rSO2S according to the type of ventilation modalities. rSO2C
HFOV, hours; median (IQR) CMV, hours; median (IQR)
rSO2S
Preoperative stabilization
Surgery
p
Preoperative stabilization
Surgery
p
81 (70–89) 82 (76–91)
61 (52–74) 65 (67–93)
b0.05 b0.05
78 (71–94) 79 (72–86)
62 (52–88) 71 (57–72)
b0.05 b0.05
rSO2C: NIRS measured cerebral oxygenation; rSO2S: NIRS measured splanchnic oxygenation; IQR: interquartile range.
Please cite this article as: Conforti A, et al, Effects of ventilation modalities on near-infrared spectroscopy in surgically corrected CDH infants, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.07.021
A. Conforti et al. / Journal of Pediatric Surgery xxx (2015) xxx–xxx Table 4 Effect of HFOV and CMV on persistence of rSO2C and rSO2S reduction in CDH patients. HFOV Persistence of rSO2C reduction, minutes; median (IQR) Persistence of rSO2S reduction, minutes; median (IQR)
2732 (970–3084) 10 (0–748)
CMV
p
0 (0–103.8) 0.003 12 (0–814)
5
This study should be considered as a pilot evaluation of the effects of diaphragmatic closure in antenatally diagnosed CDH infants. Future study is ongoing to evaluate developmental differences between patients enrolled in the VICI trial and treated with different ventilation modalities.
0.94
HFOV: high-frequency oscillatory ventilation; CMV: conventional mechanical ventilation; rSO2C: NIRS measured cerebral oxygenation; rSO2S: NIRS measured splanchnic oxygenation; IQR: interquartile range.
speculate that compression on the inferior vena cava, reducing the cardiac venous return, and the direct squeezing on renal artery, might interfere with splanchnic perfusion. Since the mean arterial blood pressure did not change appreciably after surgery, it is also possible that there was a redistribution of the cardiac output. Considering that these infants underwent surgical correction after at least 48 hours of cardiorespiratory stabilization, it appears that the even delayed surgery cannot avoid moderate changes in cerebral and splanchnic hemodynamics in infants with CDH. Therefore, it is reasonable to speculate that such changes could be more marked in the presence of cardiorespiratory instability, particularly in preterm infants who are less capable of autoregulating their cerebral and splanchnic perfusion [15]. As seen, our study confirms in CDH patients the previously reported modifications in cerebral hemodynamics observed in newborns and preterm babies during mechanical ventilation [16–19]. Furthermore, we define the role of surgery in the pathogenesis of cerebral and splanchnic hemodynamic changes in these critically ill infants. The statistically significant prolonged reduction in rSO2C observed in HFOV ventilated CDH infants compared with CMV ventilated patients is even more interesting. This observation is novel, and has not been reported in the international literature in any age group with CDH. The causes of this are not completely clear, however it could be partially explained by the recognized HFOV-related significantly decreased left ventricular cardiac output and contractility in comparison with CMV, reported by different authors in previous reports. A decrease in left ventricular cardiac output in HFOV is caused by a reduced left ventricular preload expressed as a lower left ventricular cavity dimensions at enddiastole [20]. Several investigators have found indirect evidence of decreased cardiac output and poor systemic perfusion manifesting in metabolic acidosis [21,22] and have concluded that reduction of left ventricular cardiac output may be related to impaired coronary perfusion. Furthermore, although experimental and human studies have indicated that HFOV is only lung protective when combined with an optimal lung volume or open lung strategy, the effect of this strategy on the hemodynamic stability of preterm infants has been poorly studied [23]. Our results are of clinical relevance because HFOV is now used in most neonatal and pediatric intensive care units to treat CDH infants, as first line or rescue therapy. Possible therapeutic consequences of the present data are not only to improve cardiac preload by volume administration (as is done at many centers) but also an optimization of inotropic support to improve decreased cardiac output. In conclusion, our study confirms the potential negative effects of surgery in CDH infants and its role on hemodynamic changes in those patients. Those modifications could be secondary to inferior vena cava transient compression and therefore to reduction of the cardiac venous return. It also indicates that timing of surgery is essential and not without hazard in CDH patients. Furthermore, our results suggest that HFOV plays a role in sustaining hemodynamic cerebral changes, probably in relation of a decreased left ventricular cardiac output caused by a reduced left ventricular preload.
4. Limitation The present study even if part of a prospective randomized study, was not designed to discover differences between HFOV and CMV in terms of hemodynamic changes of NIRS variation. References [1] van den Hout L, Tibboel D, Vijfhuize S, et al. The VICI-trial: high frequency oscillation versus conventional mechanical ventilation in newborns with congenital diaphragmatic hernia: an international multicentre randomized controlled trial. BMC Pediatr 2011;11:98–104. [2] Lemmers PM, Molenschot MC, Evens J, et al. Is cerebral oxygen supply compromised in preterm infants undergoing surgical closure for patent ductus arteriosus? Arch Dis Child Fetal Neonatal Ed 2010;95:F429–34. [3] Lemmers PM, Toet M, van Schelven LJ, et al. Cerebral oxygenation and cerebral oxygen extraction in the preterm infant: the impact of respiratory distress syndrome. Exp Brain Res 2006;173:458–67. [4] Hahn GH, Maroun LL, Larsen N, et al. Cerebral autoregulation in the first day after preterm birth: no evidence of association with systemic inflammation. Pediatr Res 2012;71:253–60. [5] Conforti A, Giliberti P, Mondi V, et al. Near infrared spectroscopy: experience on esophageal atresia infants. J Pediatr Surg 2014;49:1064–8. [6] Valfrè L, Braguglia A, Conforti A, et al. Long term follow-up in high-risk congenital diaphragmatic hernia survivors: patching the diaphragm affects the outcome. J Pediatr Surg 2011;46:52–6. [7] Hirsch JC, Charpie JR, Ohye RG, et al. Near-infrared spectroscopy: what we know and what we need to know—a systematic review of the congenital heart disease literature. J Thorac Cardiovasc Surg 2009;137:154–9. [8] Reiss I, Schaible T, van den Hout L, et al. Standardize postnatal management of infants with congenital diaphragmatic hernia in Europe: the CDH EURO Consortium consensus. Neonatology 2010;98:354–64. [9] Koletzko B, Goulet O, Hunt J, et al. 1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Society for Clinical Nutrition and Metabolism (ESPEN), supported by the European Society of Paediatric Research (ESPR). J Pediatr Gastroenterol Nutr 2005;41(Suppl 2):S1–4. [10] Dotta A, Rechichi J, Campi F, et al. Effects of surgical repair of congenital diaphragmatic hernia on cerebral hemodynamics evaluated by near-infrared spectroscopy. J Pediatr Surg 2005;40:1748–52. [11] Giliberti P, Mondì V, Conforti A, et al. Near infrared spectroscopy in newborns with surgical disease. J Matern Fetal Neonatal Med 2011;24(Suppl 1):56–8. [12] Bishay M, Giacomello L, Retrosi G, et al. Decreased cerebral oxygen saturation during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia in infants. J Pediatr Surg 2011;46:47–51. [13] van Bel F, van de Bor M, Baan J, et al. The influence of abnormal blood gases on cerebral blood flow velocity in the preterm newborn. Neuropediatrics 1988;19:27–32. [14] Pryds O. Control of cerebral circulation in the high-risk neonate. Ann Neurol 1991; 30:321–9. [15] Cerbo RM, Maragliano R, Pozzi M, et al. Global perfusion assessment and tissue oxygen saturation in preterm infants: where are we? Early Hum Dev 2013;89: S44–6. [16] Milan A, Freato F, Vanzo V, et al. Influence of ventilation mode on neonatal cerebral blood flow and volume. Early Hum Dev 2009;85:415–9. [17] Roche-Labarbe N, Aggarwal A, Dehaes M, et al. Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain. J Cereb Blood Flow Metab 2011;32:481–8. [18] Cambonie G, Guillaumont S, Luc F, et al. Haemodynamic features during highfrequency oscillatory ventilation in preterms. Acta Paediatr 2003;92:1068–73. [19] Noone MA, Sellwood M, Meek JH, et al. Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing highfrequency oscillatory ventilation. Acta Paediatr 2003;92:1079–84. [20] Simma B, Fritz M, Fink C, et al. Conventional ventilation versus high-frequency oscillation: hemodynamic effects in newborn babies. Crit Care Med 2000;28:227–31. [21] Froese AB, Bryan C. High frequency ventilation. Am Rev Respir Dis 1987;135: 1363–74. [22] Meredith KS, deLemos RA, Coalson JJ, et al. Role of lung injury in the pathogenesis of hyaline membrane disease in premature baboon. J Appl Physiol 1989;66:2150–8. [23] De Waal K, Evans N, Van Der Lee J, et al. Effect of lung recruitment on pulmonary, systemic, and ductal blood flow in preterm infants. J Pediatr 2013;154:651–5.
Please cite this article as: Conforti A, et al, Effects of ventilation modalities on near-infrared spectroscopy in surgically corrected CDH infants, J Pediatr Surg (2015), http://dx.doi.org/10.1016/j.jpedsurg.2015.07.021