Mariam M. Said

Monitoring mesenteric tissue oxygenation with near-infrared spectroscopy during packed red blood cell transfusion in preterm infants

OBJECTIVE To monitor altered mesenteric tissue oxygen saturation (StO2) before and after blood transfusion. METHODS We placed a 4-wavelength NIRS sensor (FORE-SIGHT, CASMED, Branford, CT USA) on the right lower abdominal quadrant prior to transfusion and measured StO2 for up to 48 hours post transfusion. Pulse oximetry (SpO2) data was collected simultaneously, with fractional tissue oxygen extraction (FTOE) and the [SpO2-StO2] difference calculated to normalize for hypoxic episodes. All data was combined and averaged in 30 minute windows for events before, during, and post transfusion to determine long term trends and analyzed using Repeated Measures ANOVA. 24 infants were enrolled in this study with 36 hours of data collected for 23 subjects and 48 hours for 16 subjects. RESULTS We found no significant differences in any of the parameters when compared pre and post transfusion values at 3, 6, 12, 24 and 36 hours post transfusion. For the 16 subjects monitored to 48 hours, there was a significant decrease in FTOE and near significant increase in StO2 and reciprocal decrease in [SpO2 - StO2] at 48 hours post transfusion. CONCLUSIONS There are several plausible mechanisms that may explain the relationship between necrotizing enterocolitis and PRBC transfusion; however, mesenteric tissue oxygen saturation changes did not clearly show that ischemia or re-perfusion injury to be one of the potential mechanisms.

Validation of near infrared spectroscopy to measure abdominal somatic tissue oxygen saturation in neonates.

OBJECTIVE In this study, we validated the use of the FORE-SIGHT® (CAS Medical Systems, Branford, CT USA) tissue oximeter monitor on abdominal tissue oxygenation in infants ≤4 kg using a stool-interference compensation algorithm. STUDY DESIGN A total of 40 neonates with an umbilical venous catheter (UVC) were enrolled in this study. We measured abdominal tissue saturation (StO2) values using FORE-SIGHT, and compared to a Reference StO2 value derived from weighted co-oximetry values from the UVC and pulse oximeter measurements. RESULTS There was a strong correlation between NIRS calculated StO2 measurements when compared with the reference StO2, with an overall bias (sd) of -0.77 (5.06)% and a concordance correlation coefficient (CCC) of 0.789. CONCLUSION Data from this validation study suggest that the FORE-SIGHT monitor, which compensates for the optical properties of stools in neonates, can yield accurate measures of abdominal tissue oxygen saturation.

Are Immune Modulating Single Nucleotide Polymorphisms Associated with Necrotizing Enterocolitis

Necrotizing enterocolitis (NEC) is a devastating gastrointestinal emergency. The purpose of this study is to determine if functional single nucleotide polymorphisms (SNPs) in immune-modulating genes pre-dispose infants to NEC. After Institutional Review Board approval and parental consent, buccal swabs were collected for DNA extraction. TaqMan allelic discrimination assays and BglII endonuclease digestion were used to genotype specific inflammatory cytokines and TRIM21. Statistical analysis was completed using logistic regression. 184 neonates were analyzed in the study. Caucasian neonates with IL-6 (rs1800795) were over 6 times more likely to have NEC (p = 0.013; OR = 6.61, 95% CI 1.48–29.39), and over 7 times more likely to have Stage III disease (p = 0.011; OR = 7.13, (95% CI 1.56–32.52). Neonates with TGFβ-1 (rs2241712) had a decreased incidence of NEC-related perforation (p = 0.044; OR = 0.28, 95% CI: 0.08–0.97) and an increased incidence of mortality (p = 0.049; OR = 2.99, 95% CI: 1.01 – 8.86). TRIM21 (rs660) was associated with NEC-related intestinal perforation (p = 0.038; OR = 4.65, 95% CI 1.09–19.78). In premature Caucasian neonates, the functional SNP IL-6 (rs1800795) is associated with both the development and increased severity of NEC. TRIM21 (rs660) and TGFβ-1 (rs2241712) were associated with NEC- related perforation in all neonates in the cohort. These findings suggest a possible genetic role in the development of NEC.

Evaluation of the new generation dual-lumen catheter for neonatal ECMO

Objectives: The purpose of this study was to compare the newly designed dual-lumen venovenous catheter (VR13, OriGen Biomedical, Austin, TX) with the current dual-lumen catheter (VV12, OriGen Biomedical). Methods: Five newborn lambs, 1 to 5 days old and weighing 4.2 ± 0.5 kg, were cannulated with the VV13 OriGen catheter and placed on extracorporeal membrane oxygenation (ECMO). ECMO flows were increased from 200 to 600 ml/min, with measurements taken after the changes. The experiment was then repeated using the VV12 catheter. Results: Recirculation values were equal for both catheters. The pressure drop at the reinfusion port was equal for both catheters at 200 ml/min, increasing to 275 mmHg at 500 ml/min for the VR13 vs. 240 mmHg for the VV12 catheter. Conclusion: These findings indicate that the VR13 catheter resulted in levels of recirculation equal to the VV12. Based on resistance measurements, we do not recommend the use of this new catheter beyond 400 ml/min until minor design changes are made.

Genomics In Premature Infants: A Non-Invasive Strategy To Obtain High-Quality DNA

We used a cost-effective, non-invasive method to obtain high-quality DNA from buccal epithelial-cells (BEC) of premature infants for genomic analysis. DNAs from BEC were obtained from premature infants with gestational age ≤ 36 weeks. Short terminal repeats (STRs) were performed simultaneously on DNA obtained from the buccal swabs and blood from the same patient. The STR profiles demonstrated that the samples originated from the same individual and exclude any contamination by external DNAs. Whole exome sequencing was performed on DNAs obtained from BEC on premature infants with and without necrotizing enterocolitis, and successfully provided a total number of reads and variants corroborating with those obtained from healthy blood donors. We provide a proof of concept that BEC is a reliable and preferable source of DNA for high-throughput sequencing in premature infants.

Testing a new NIRS method to measure regional mesenteric tissue oxygen saturation in preterm infants that compensates for meconium and transitional stool interference.

Objective: Simultaneous monitoring of cerebral and mesenteric tissue saturations were recorded in preterm neonates using near infrared spectroscopy (NIRS) to evaluate if NIRS method can be improved to compensate for the optical absorption properties of stool interference, particularly meconium and transitional stools, in order to reliably measure gastrointestinal (GI) tissue oxygen saturation. Study design: With parental agreement, we used a 4-wavelength cerebral & tissue oximeter (FORE-SIGHT ® , CAS Medical Systems, Branford, CT USA) to monitor premature neonates. The NIRS sensors were placed in the right lower quadrant of the abdomen and the forehead, with continuous data collection every 2 seconds for 72 hours. Simultaneously, continuous peripheral pulse oximetry (SpO2) was recorded. Feeding regimens, stooling patterns and clinical outcomes were recorded. Raw data from FORE-SIGHT were recorded and analyzed using a prototype neonatal stool compensation algorithm. Results: Twenty-three preterm neonates with adjusted gestational ages of 26-34 weeks, weighing 740-1930 grams were studied. NIRS stool interference level was determined for all subjects, and found to be extremely variable. High and Very High stool interference occurred for subjects passing meconium. Moderate and High stool interference resulted in erroneously computed very low GI StO2 using traditional NIRS methods. Stool compensated GI StO2 measurements showed a higher correlation to cerebral SctO2 and pulse oximetry SpO2 in subjects with healthy bowel. Conclusion: Measurement of mesenteric saturations via NIRS proves to be a useful tool in neonates. A NIRS algorithm that compensates for interference caused by meconium and transitional stools shows promising results to measure GI StO2 accurately.

Changes in Autonomic Tone in Premature Infants Developing Necrotizing Enterocolitis

Background Necrotizing enterocolitis (NEC) is a complication of prematurity with a high mortality rate. Currently, there are no reliable biomarkers capable of identifying infants at risk for developing NEC. We sought to determine the autonomic nervous system antecedents of NEC in premature infants, using heart rate variability (HRV). Materials and Methods HRV was quantified by retrieving archived electrocardiogram (EKG) data from 30 premature infants from 4 days prior, through 4 days after, the clinical NEC diagnosis. HRV metrics were compared with those on the diagnosis day using the receiver operating characteristic (ROC) analysis. Results HRV metrics showed a depression of autonomic tone that preceded the clinical NEC diagnosis by 2 days, and which recovered to baseline by 2 days after diagnosis (area under the curve [AUC] < 0.7). The pattern of HRV change was significantly associated with the clinical severity of NEC (stage II vs. stage III). Conclusion Our studies suggest that readily accessible metrics of autonomic depression might expedite the diagnosis of NEC and its severity in a clinically meaningful manner. Clearly, these studies need to be extended prospectively to determine the diagnostic utility of this approach.

Influence of central hemodynamics on VV ECMO oxygen delivery in neonatal animal model.

BACKGROUND Recirculation of oxygenated blood in venovenous extracorporeal membrane oxygenation (VV ECMO) can decrease the oxygen delivery provided by the ECMO support. This study investigated the influence of central hemodynamics and catheter position on the amount of recirculation and oxygen delivery during VV ECMO. METHODS Recirculation was measured in seven newborn lambs (mean weight 4.7 kg) during VV ECMO using the ELSA Monitor (Transonic Systems, Inc., Ithaca, NY) and using the central venous line (CVL) method. The ECMO pump was set at the prescribed flow of 110-120 mL/kg/min for a targeted oxygen delivery rate of 6cc/kg/min without recirculation. Hemodynamic status before and during ECMO was also measured by the COstatus Monitor (Transonic Systems, Inc.,Ithaca, NY). RESULTS Lambs with a higher cardiac index (>160 ml/min/kg), had a tendency to have higher percent oxygen delivery (65-94%, at prescribed flow) while lambs with lower cardiac index (<150 ml/min/kg), tended to have lower percent oxygen delivery (39-62%, at prescribed flow). ELSA recirculation measurements had a squared correlation coefficient R2 = 0.8 with the CVL method. CONCLUSIONS The ELSA monitor provides an easy to use, non-invasive method to measure recirculation in VV ECMO. The data suggests that cardiac function may play an important prognostic role in achieving effective VV ECMO support.

In vitro and in vivo assessment of oxygenator blood volume for the prediction of clot formation in an ECMO circuit (theory and validation)

Introduction: Clotting is one of the major causes of mortality and morbidity during extracorporeal membrane oxygenation (ECMO). A large meta-analysis study suggests that 29% of patients require the oxygenator to be replaced during ECMO. As clots usually form in the oxygenator, the oxygenator blood volume (OXBV) decreases over time. The currently used pressure gradient as a predicator of clot formation is unreliable. Objective: The aim of this study was to develop and validate ultrasound dilution technology in a quantitative assessment of clotting, using measurements of OXBV. Methods: OXBV was measured using the ELSA monitor (Transonic Systems Inc., Ithaca, NY, USA) from the transit time of a saline bolus passing through the oxygenator as recorded by a sensor placed after the oxygenator. The accuracy and reproducibility (coefficient of variation [CV]) of OXBV measurement and its independence from ECMO flow was assessed in vitro in lambs and from a clinical data archive. Results: The in vitro accuracy compared with volumetric measurements of OXBV of 22-134 ml at flows of 300-700 ml/min was −0.8±6.6%. For an OXBV of 355 ml at flows of 1020-7000 ml/min, accuracy was −0.4±1.6%. In 88 animal OXBV measurements, the CV was 1.49±1.12%. For an OXBV of 153 (range 42-387 ml), clinical measurements at flow ranged from 210-5960 ml/min, with a CV of 3.20±2.44 %. Conclusion: Dilution technology has the ability to accurately and reproducibly assess the clotting process in the oxygenator. Larger studies are needed to establish guidelines for the prediction of imminent clotting and may help to avoid unnecessary circuit changes.