Michelle E. van der Laan

A Hemodynamically Significant Patent Ductus Arteriosus Does Not Affect Cerebral or Renal Tissue Oxygenation in Preterm Infants

Background: Patent ductus arteriosus (PDA) is common in preterm infants and is associated with significant morbidity. To determine whether the PDA is hemodynamically significant (HSDA), several echocardiographic parameters have been suggested, including retrograde diastolic blood flow in the descending aorta (Dao). Objective: To assess the impact of an HSDA, including retrograde diastolic flow in the Dao, on regional tissue oxygen saturation (rSO2) and extraction measured by near-infrared spectroscopy (NIRS). Methods: This is a prospective observational cohort study in which we included preterm infants (GA <32 weeks) who underwent echocardiographic screening because of clinical signs of an HSDA within 2 weeks after birth. We measured cerebral and renal rSO2 on the day of echocardiography. HSDA was diagnosed if left-to-right shunting through the PDA was accompanied by left atrial-to-aortic root ratio >1.4 and/or left pulmonary artery end-diastolic flow velocity >0.2 m/s and/or retrograde diastolic blood flow in the Dao. Results: Forty-nine infants were included, with a median GA of 27.6 weeks (IQR: 26.1-29.0), birth weight of 980 g (IQR: 800-1,200), and postnatal age of 77 h (IQR: 70-107). Infants with a closed duct (n = 11), a non-HSDA (n = 18), and an HSDA (n = 20) had similar cerebral and renal NIRS measurements. Retrograde diastolic blood flow in the Dao, present in 11 infants with PDA, also did not affect cerebral and renal NIRS measurements. Conclusion: In preterm infants with clinical signs of an HSDA within 2 weeks after birth, cerebral and renal oxygen saturation and extraction are not affected by an HSDA or by retrograde diastolic blood flow in the Dao.

Effect of balloon atrial septostomy on cerebral oxygenation in neonates with transposition of the great arteries.

Background:The aim of this study was to determine the effect of balloon atrial septostomy (BAS) on cerebral oxygenation in neonates with transposition of the great arteries (TGA).Methods:In term neonates with TGA, regional cerebral tissue oxygen saturation (rcSO2) was measured using near-infrared spectroscopy (NIRS) for a period of 2 h, before BAS, after BAS, and 24 h after BAS. In neonates who did not require BAS on clinical grounds, rcSO2 was measured within 24 h of admission and 24 h later.Results:BAS was performed in 12 of 21 neonates. rcSO2 increased from a median of 42% (before) to 48% at 2 h after BAS (P < 0.05), as did transcutaneous arterial oxygen saturation (spO2) (from 72% to 85%, P < 0.01). rcSO2 increased further during the next 24 h (from 48% to 64%, P < 0.05), whereas spO2 remained stable. Although beginning from a lower baseline (42 vs. 51%, P < 0.01), rcSO2 was higher in neonates treated with BAS, as compared with neonates not treated with BAS, 24 h after the procedure (64 vs. 58%, P < 0.05); spO2 was, however, similar between the two groups.Conclusion:BAS improves cerebral oxygen saturation in neonates with TGA. Complete recovery of cerebral oxygen saturation occurred only 24 h after BAS.

Volume Expansion Does Not Alter Cerebral Tissue Oxygen Extraction in Preterm Infants with Clinical Signs of Poor Perfusion

Background: Preterm infants with signs of poor perfusion are often treated with volume expansion, although evidence regarding its effect on cerebral perfusion is lacking. Moreover, the effect is questionable in preterm infants with an adequate cerebrovascular autoregulation (CAR). A useful measure to assess perfusion is cerebral fractional tissue oxygen extraction (cFTOE). Objectives: To assess the effect of volume expansion on cFTOE in preterm infants with signs of poor perfusion. Methods: In this observational study, we assessed cFTOE using near-infrared spectroscopy in preterm infants with signs of poor perfusion before, during and 1 h after volume expansion treatment. Simultaneously, we measured mean arterial blood pressure (MABP). We tested the effect of volume expansion on both cFTOE and MABP, using multi-level analyses. We intended to define a subgroup that responded to volume expansion with an increase in blood pressure and a decrease in cFTOE, suggesting absent CAR. Results: In 14 preterm infants, with a median gestational age of 26.7 weeks (25.0-28.7 weeks) and a median birth weight of 836 g (615-1,290 g), we found a small increase in MABP during (1.4 ± 1.4 mm Hg, p = 0.003) and after (1.8 ± 1.7 mm Hg, p = 0.001) volume expansion, but no change in cFTOE during (-0.19 ± 0.1% p = 0.44) or after (-0.53 ± 0.1% p = 0.34) volume expansion. We were unable to define a subgroup lacking CAR. Conclusions: Cerebral perfusion, as assessed by cFTOE, does not improve in preterm infants with signs of poor perfusion following volume expansion. In these infants, either CAR is present or volume expansion is inadequate to affect cFTOE.

Assessing cerebrovascular autoregulation in infants with necrotizing enterocolitis using near-infrared spectroscopy

Background:We assessed cerebrovascular autoregulation (CAR) in preterm infants with definite necrotizing enterocolitis (NEC), Bell’s stage 2 or 3, and infants without NEC, using near-infrared spectroscopy. We hypothesized that CAR would be more often impaired in infants with NEC compared with infants without NEC.Methods:We measured cerebral regional tissue oxygen saturation, arterial oxygen saturation, and mean arterial blood pressure (MABP) during 48 h. We calculated the correlation between cerebral fractional tissue oxygen extraction and MABP for each patient. A statistically significant negative correlation reflected impaired CAR.Results:We included 15 infants with definite NEC (median (range) gestational age 27.4 (25.6–34.7) wk; birth weight 1,070 (670–2,400) g) and 13 infants without NEC (gestational age 27.9 (26.3–34.7) wk; birth weight 980 (640–2,640) g). Fourteen infants had a statistically significant negative correlation (ρ −0.468 to−0.104), of whom five were infants without NEC (5/13; 38%) and nine with definite NEC (9/15; 60%). The difference in prevalence of impaired CAR was not statistically significant.Conclusion:Impaired CAR is present in a substantial proportion of infants with definite NEC, which may predispose them to NEC-associated neurological damage.

Near-Infrared Spectroscopy to Predict the Course of Necrotizing Enterocolitis

Objectives To investigate whether cerebral, liver, and infraumbilical regional tissue oxygen saturation (rSO2) and fractional tissue oxygen extraction (FTOE) could be used to diagnose necrotizing enterocolitis (NEC) and complicated NEC (Bell’s stage 3B or death) during its early stages. Methods A prospective observational cohort study of preterm infants with suspected or diagnosed NEC. We compared the mean eight-hour cerebral, liver, and infraumbilical rSO2 and FTOE values of infants with no NEC and definite NEC and of infants with uncomplicated and complicated NEC in the first forty-eight hours after onset of symptoms, suspicious for NEC. Furthermore, we determined cut-off values by generating receiver operating characteristics curves in case of significant differences in the first eight-hour mean values of rSO2 between infants with no NEC and definite NEC and between infants with uncomplicated and complicated NEC. Results We included 33 patients: 13 no NEC, 10 with uncomplicated NEC, and 10 with complicated NEC. We found no significant differences in the first twenty-four hours after onset of symptoms in rSO2 and FTOE between infants with no NEC and definite NEC. In preterm infants with complicated NEC, we observed significantly lower cerebral, liver, and infraumbilical rSO2 and higher FTOE within twenty-four hours after onset of symptoms compared with infants with uncomplicated NEC. A continuous cerebral rSO2 ≤ 71% and liver rSO2 ≤ 59% in the first eight hours after onset of symptoms predicted the onset of complicated NEC with a sensitivity of 1.0 and specificity of 0.8, and a sensitivity of 1.0 and specificity of 1.0, respectively. Conclusions By measuring the cerebral and splanchnic oxygenation it is possible to differentiate complicated NEC from uncomplicated NEC. In our sample, NIRS monitoring did not proof useful for distinguishing between definite NEC and no NEC in preterm infants with clinical signs suspicious of NEC.

Abdominal near-infrared spectroscopy in preterm infants: A comparison of splanchnic oxygen saturation measurements at two abdominal locations

BACKGROUND Splanchnic tissue oxygenation monitoring has been performed at both the liver and the infra-umbilical regions. It is unknown whether these measurements could be substituted one for the other when interpreting splanchnic oxygenation since they have not been measured simultaneously before. AIMS To evaluate the feasibility and safety of liver and infra-umbilical near-infrared spectroscopy (NIRS) monitoring in preterm infants with suspected necrotizing enterocolitis (NEC) and to assess the correlation and agreement between NIRS measurements performed simultaneously at the two abdominal locations. STUDY DESIGN AND SUBJECTS This study was part of a prospective observational cohort study. Preterm infants who were suspected of NEC or who had been diagnosed with NEC were included. OUTCOME MEASURES Liver oxygen saturation and infra-umbilical oxygen saturation were monitored simultaneously and continuously for 48h by NIRS. RESULTS NIRS monitoring was performed in 20 out of 24 infants for the entire 48-hour study period. No adverse effects were observed. Values of liver and infra-umbilical oxygen saturation correlated weakly (Spearmans rho=0.244, P<.001). On the Bland-Altman plot liver oxygen saturation was higher than infra-umbilical oxygen saturation (mean difference 6.6%, SD 22.5%). CONCLUSIONS Using NIRS as method for monitoring oxygen saturation simultaneously in both the liver and infra-umbilical regions is safe and feasible. Additionally, we demonstrated that values of liver and infra-umbilical oxygen saturation cannot be randomly substituted one for the other for the purpose of assessing splanchnic oxygenation.

Cerebral oxygen saturation during the first 72h after birth in infants diagnosed prenatally with congenital heart disease

BACKGROUND Evidence suggests that hypoxic-ischemic brain injury in infants with congenital heart disease already occurs during early life. The aim of our study was, therefore, to assess the course of regional cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) during the first 72h after birth in infants with prenatally diagnosed duct-dependent congenital heart disease. In addition, we identified clinical parameters that were associated with rcSO2. MATERIALS AND METHODS We included 56 infants with duct-dependent congenital heart disease. We measured arterial oxygen saturation (SpO2) and rcSO2 during the first 72h after birth. Simultaneously, we calculated FTOE. RESULTS We observed median rcSO2 values of approximately 60%, a decreasing FTOE from 0.34 on day 1 to 0.28 on day 3 and stable preductal SpO2 values around 90%. Several clinical variables were associated with rcSO2. In a multiple linear regression model only type of CHD and preductal SpO2 were significant predictors of rcSO2 during the first three days after birth. Infants with a duct-dependent pulmonary circulation had up to 12% lower rcSO2 values than infants with a duct-dependent systemic circulation. CONCLUSION We demonstrated that, during the first three days after birth, cerebral oxygen saturation is low in infants with duct-dependent congenital heart disease. Furthermore, this study provides preoperative reference values of rcSO2 and FTOE in infants with duct-dependent CHD.

The Association between Multisite Near-Infrared Spectroscopy and Routine Hemodynamic Measurements in Relation to Short-Term Outcome in Preterms with Clinical Sepsis

Background: The added clinical value of multisite near-infrared spectroscopy (NIRS) monitoring to detect low organ tissue perfusion in preterm infants at risk of circulatory failure remains unclear. Objectives: To evaluate the associations between multisite NIRS measurements and clinical signs of circulatory failure in relation to short-term outcome in preterm infants with clinical sepsis. Methods: Prospective cohort study of preterm infants (gestational age <32 weeks) with clinical sepsis. We monitored cerebral, renal, and intestinal oxygen saturation using NIRS for 72 h following sepsis workup and calculated fractional tissue oxygen extraction (FTOE). We recorded clinical signs of circulatory failure every 8 h. We analyzed the associations between FTOE values, clinical signs of circulatory failure, and short-term outcome. Results: In 28 preterm infants with clinical sepsis, intraindividual and interindividual associations between NIRS values and clinical signs of circulatory failure were weak. At several points of time during the study period, cerebral and renal FTOE were higher in infants who developed intestinal complications compared with infants who did not, while clinical signs of circulatory failure never differed between groups. After correcting for multiple testing, significant differences disappeared. Conclusions: The associations between multisite FTOE values and clinical signs of circulatory failure were weak in preterm infants with clinical sepsis. Nevertheless, in contrast to clinical signs of circulatory failure, cerebral and renal FTOE values were associated with adverse short-term intestinal outcome in the uncorrected analyses. Multisite NIRS monitoring might help to detect critically low tissue oxygen delivery leading to adverse intestinal outcome not detected by routine hemodynamic measurements.

Multisite Tissue Oxygenation Monitoring Indicates Organ-Specific Flow Distribution and Oxygen Delivery Related to Low Cardiac Output in Preterm Infants With Clinical Sepsis

Objectives: Cardiac output may be compromised in preterm infants with sepsis. Whether low cardiac output is associated with low tissue oxygen supply in these patients is unclear. The aim of the current study was to assess the association between cardiac output, assessed by echocardiography, and tissue oxygenation, measured with multisite near-infrared spectroscopy, in a cohort of preterm infants with clinical sepsis. Design: Prospective observational cohort study. Setting: Level III neonatal ICU. Patients: Twenty-four preterm infants (gestational age < 32 wk) with clinical sepsis. Interventions: None. Measurements and Main Results: Clinical and echocardiographic assessment of hemodynamics was performed within 48 hours of sepsis workup and repeated at least 24 hours later. We measured cerebral, renal, and intestinal tissue oxygen saturation using near-infrared spectroscopy during an hour of stable measurements directly preceding or following echocardiography and calculated fractional tissue oxygen extraction in each tissue. We determined Spearman correlation coefficients between fractional tissue oxygen extraction and right ventricular output corrected for patent foramen ovale flow, left ventricular output corrected for ductus arteriosus flow, and superior vena cava flow. Right ventricular output corrected for patent foramen ovale and left ventricular output corrected for ductus arteriosus flow both correlated significantly with intestinal fractional tissue oxygen extraction (&rgr;, –0.700; p = 0.036 and &rgr;, –0.604; p = 0.029, respectively). In contrast, no significant correlations were found between cardiac output measurements and cerebral and renal fractional tissue oxygen extraction, respectively. Changes in cardiac output measurements were not associated with observed changes in fractional tissue oxygen extraction values. Conclusions: Right ventricular output corrected for patent foramen ovale and left ventricular output corrected for ductus arteriosus flow, indicators of systemic blood flow in preterm infants with shunts, were negatively associated with intestinal fractional tissue oxygen extraction, but not with renal and cerebral fractional tissue oxygen extraction. These findings suggest that during low output states due to clinical sepsis intestinal perfusion is most at risk.

The relation between splanchnic ischaemia and intestinal damage in necrotising enterocolitis

Objectives The underlying pathophysiology of necrotising enterocolitis (NEC) remains incompletely understood, particularly the role of intestinal perfusion. We aimed to determine the relation between cerebral and splanchnic fractional tissue oxygen extraction (FTOE), a marker for tissue underperfusion, with intestinal fatty acid-binding protein in plasma (I-FABPp), a marker for intestinal damage, in infants with NEC. Furthermore, we investigated the combined courses of cerebral and splanchnic FTOE values and I-FABPp levels in uncomplicated (conservative treatment) and complicated NEC (surgery or death). Design This study was part of a prospective observational cohort study. Patients We included 19 preterm infants with NEC (9 uncomplicated, 10 complicated). Interventions Using near-infrared spectroscopy, we measured regional cerebral and splanchnic tissue oxygen saturations continuously for 48 h after NEC onset. We measured I-FABPp levels simultaneously. Main outcome measures We used Spearman correlation tests to calculate correlation coefficients between FTOE values and I-FABPp levels in uncomplicated and complicated NEC. Results Median (range) gestational age was 28 (25–36) weeks and median (range) birth weight was 1290 (740–2400) g. Cerebral and splanchnic FTOE values correlated strongly with I-FABPp levels (rho between .745 and 0.900; p<0.001–0.037) during the first 16 h after NEC onset. Thereafter, in uncomplicated NEC, splanchnic FTOE values increased while I-FABPp levels decreased concomitantly. In complicated NEC both splanchnic FTOE values and I-FABPp levels decreased. Conclusions Combining cerebral and splanchnic FTOE values with I-FABPp levels, gives insight in the pathological chain of events resulting in progression or recovery of intestinal ischaemia in NEC. Trial registration number NTR3239.