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Case of the Month

Abnormal Splanchnic Regional Saturations in a Preterm Infant That Developed Necrotizing Enterocolitis Following a Red Blood Cell Transfusion

Baserga, Mariana MD, MSCI; Reich, Brixen MSN, RNC-NIC, CCRC; Braski, Katherine MD

Editor(s): Newberry, Desi M. DNP, NNP-BC, Section Editor

Author Information
doi: 10.1097/ANC.0000000000000711
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Abstract

Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency encountered in the newborn intensive care unit and represents a significant cause of morbidity and mortality in premature infants.1 The sequence of events leading to NEC appears to be multifactorial and complex.2,3 While epidemiologic studies have identified multiple factors that appear to increase an infant's risk for the development of NEC, other than prematurity, no single predictive risk factor has been clearly delineated.4,5 A significant association between elective red blood cell (RBC) transfusion and the subsequent development of NEC has been consistently observed in premature infants. In these reports, 25% to 40% of all NEC cases developed within 48 hours of an RBC transfusion.6–12

Near-infrared spectroscopy (NIRS) is a noninvasive bedside technology that allows for real-time determination of the oxygenation status of hemoglobin, reported as regional oxygen saturation (rSO2) in body tissues such as the brain, and gut.13–15 NIRS rSO2 is reflective of the balance between tissue oxygen supply and demand, which can be altered by neonatal pathologies such as NEC and anemia.16,17 Normal cerebral and splanchnic rSO2 have not been fully defined in premature neonates. Studies have reported values from 32% to 66% for splanchnic rSO2 and from 66% to 83% for cerebral rSO2 in nonanemic neonates, with lower saturations seen in neonates requiring transfusion.18–21

The splanchnic-cerebral oxygenation ratio (SCOR) compares the splanchnic oxygenation to cerebral oxygenation, and has been proposed as a means of predicting gut ischemia.14

In this report we describe the presentation of NEC following a RBC transfusion in a premature neonate being monitored with cerebral and splanchnic NIRS.

CASE REPORT

This premature infant was a 286/7-week, 890-g, female born to a 23-year-old Caucasian mother with normal prenatal laboratory values via C-section secondary to preeclampsia. Delivery and resuscitation were uneventful, Apgar scores were 7 (1 minute) and 8 (5 minutes), and the infant was intubated for surfactant administration and then extubated to continuous positive airway pressure for respiratory insufficiency shortly after birth and transitioning to nasal cannula by day of life 9. She received 48 hours of ampicillin and gentamicin following delivery. Enteral feedings with human milk were initiated shortly after birth and advanced without problem to full feedings fortified with human milk fortification to 24 calories by day of life 14. By day of life 29, this infant was requiring a small amount of supplemental oxygen by nasal cannula (3/4 L, 21%-25% FiO2) and had been tolerating bolus human milk enteral feedings (150 mL/kg/day) every 3 hours. However, later that day, the infant developed increased apnea/bradycardia episodes from baseline and her hematocrit was found to be 27% on a screening complete blood count performed for ruling out sepsis. The decision was made by the clinical team to give a 15-mL/kg RBC transfusion (irradiated RBC, 5-day length of storage). The feedings were held for 6 hours prior to initiation of the RBC transfusion, which was delivered over 3 hours. Enteral feedings were resumed 3 hours following completion of the transfusion per the attending neonatologist. Twenty-four hours following completion of the RBC transfusion, the infant developed abdominal distension and passed a bloody stool. An abdominal x-ray was consistent with pneumatosis (Bell's stage 2 NEC). The infant developed progressive respiratory failure requiring intubation and conventional mechanical ventilation. Due to the diagnosis of NEC, the infant completed 7 days of vancomycin and piperacillin-tazobactam (Zosyn); blood cultures remained negative. The infant was extubated after 4 days of mechanical ventilation and feedings were held for 7 days following resolution of pneumatosis on abdominal x-ray. Enteral feedings were resumed on day of life 40 and the infant tolerated a slow increase back to full feedings and fortification without evidence of intolerance. Peripherally inserted central catheter line for parenteral nutrition was removed on day of life 45. The infant was subsequently discharged on room air and full oral feedings on day of life 70.

INTERVENTIONS

This infant's cerebral and splanchnic rSO2 levels were monitored via NIRS as part of a research study evaluating splanchnic saturations around the time of RBC transfusions. This study had received internal review board approval.

The neonatal intensive care unit (NICU) research nurse coordinators screened all infants born at less than 32 weeks' gestational age who required a RBC transfusion for eligibility as part of this prospective observational study. Infants with multiple congenital anomalies, history of NEC, ongoing sepsis, and/or a large patent ductus arteriosus (PDA) were excluded. After informed parental consent was obtained, infants were monitored using an INVOS 5100 C-4 (Medtronic, Minneapolis, Minnesota) NIRS monitor. The research nurses placed the neonatal NIRS probes according to INVOS OxyAlert protocols on intact skin over the right or left frontal area (cerebral rSO2) and the infraumbilical area of the abdomen (splanchnic rSO2). The regional saturation readings were covered throughout the study period so that the clinical team was blinded to the NIRS results.

rSO2 (cerebral and splanchnic) measurements were continuously recorded every 5 seconds throughout the monitoring period. Once the monitoring period was completed, the research nurse downloaded the rSO2 data for analyses. The rSO2 data were averaged into 30-minute periods throughout the observation period. These averages were then reported in 30-minute periods at baseline (prior to packed RBC transfusion), 1.5-hour periods during the RBC transfusion, and 3-hour periods for the 48 hours following the transfusion. Splanchnic-cerebral oxygenation ratio was calculated (rSO2 splanchnic/rSO2 cerebral) for each of the 30-minute periods.

NIRS MONITORING RESULTS

Figure 1 depicts the average cerebral and splanchnic regional saturations of the patient described. Table 1 summarizes the NIRS results. The NIRS data for this patient demonstrated slightly low baseline splanchnic saturations preceding the RBC transfusion (46.5% ± 4%), which subsequently increased during the RBC transfusion. However, in the 3 to 6 hours following the transfusion, there was a dramatic decrease in splanchnic saturations (26.5% ± 6%) and SCOR (0.37 ± 0.1), which persisted in the posttransfusion period (28.6% ± 9%/0.40 ± 0.1, respectively).

FIGURE 1
FIGURE 1:
Average cerebral and splanchnic rSO2 data. (A) transfusion, (B) feedings restarted, (C) bloody stool and abnormal abdominal x-ray, and (D) intubation.
TABLE 1. - Near-Infrared Spectroscopy Results
rSO2 Cerebral, % Mean ± SD rSO2 Splanchnic, % Mean ± SD SCOR Mean ± SD
Baseline 62.3 ± 2 46.5 ± 4 0.75 ± 0.04
Transfusion
0-1.5 h
1.5-3 h

62.7 ± 1
65.3 ± 1

56.4 ± 7
65.0 ± 4

0.90 ± 0.1
0.99 ± 0.06
Posttransfusion
0-3 h
3-6 h (feeds restarted)
6-9 h

71.1 ± 2
72.4 ± 4
71.7 ± 3

56.7 ± 7
26.5 ± 6
28.6 ± 9

0.80 ± 0.09
0.37 ± 0.1
0.40 ± 0.1
NEC diagnosis
0-3 h
3-6 h (intubation)
6-9 h

61.1 ± 4
60.8 ± 5
72.1 ± 4

33.1 ± 3
59.0 ± 14
61.0 ± 6

0.54 ± 0.06
0.99 ± 0.29
0.85 ± 0.06
Abbreviations: NEC, necrotizing enterocolitis; SCOR, splanchnic-cerebral oxygenation ratio.

At the time of NEC diagnosis, the patient had a bloody stool and abnormal abdominal x-ray, which was followed by clinical deterioration and apnea requiring intubation. The NIRS parameters did show a trend toward normalization following intubation, nothing-by-mouth status, and antibiotic treatment (Figure 1).

DISCUSSION

This case report demonstrates abnormal NIRS monitoring data in a relatively stable, growing 4-week-old premature infant who developed NEC within 24 hours of an RBC transfusion.

Multiple studies have demonstrated a temporal association between RBC transfusions in premature neonates and the development of NEC.6–11

Using NIRS a previous report had shown that normal splanchnic rSO2 ranged between 32% and 66% in neonates between 24 and 36 weeks' gestation.21 Our patient's pretransfusion values were near the lower end of this range and posttransfusion increased toward the upper end of the range.

NIRS has also been previously used to monitor cerebral and splanchnic rSO2 in neonates receiving RBC transfusions. In these studies, pretransfusion splanchnic rSO2 ranged from 41% to 54%, increased posttransfusion to 52% to 70%, and remained increased for the duration of monitoring posttransfusion (1-24 hours).18–20 These results are also consistent with our patient's initial NIRS data of pretransfusion splanchnic rSO2 of 46%, which increased during RBC transfusion to 56% to 64%.

The increase in rSO2 during transfusion is likely reflective of an increased oxygen delivery associated with increased hematocrit and oxygen-carrying capacity following the RBC transfusion. However, contrary to prior studies, which demonstrated a sustained (up to 24 hours) increase in rSO2 following transfusion, our patient had a dramatic decrease in splanchnic rSO2 starting 3 hours posttransfusion. Since this infant was part of an ongoing observational study, bedside nurses and physicians were blinded to the NIRS readings. So, as planned by the clinical team, enteral feedings were restarted 3 to 4 hours posttransfusion, a time when splanchnic rSO2 was much lower than the pretransfusion baseline. Importantly, this decrease in splanchnic rSO2, seen on NIRS, occurred approximately 15 hours prior to the infant's first clinical signs of illness/NEC. Lastly, cerebral rSO2 also increased following the RBC transfusion. There was a subsequent decrease noted around the time the infant developed clinical signs of NEC and apnea requiring intubation. This is consistent with prior studies that have demonstrated decreased cerebral rSO2 with apnea.15,22,23

The baseline SCOR of 0.75 initially increased with the RBC transfusion to 0.99, but subsequently decreased to 0.37 following transfusion. This is of concern since in prior studies an SCOR of less than 0.75 has been shown to predict gut ischemia in neonates.24 The SCOR value in our case report was borderline low at baseline, transiently improved with transfusion but then decreased far below the threshold for prediction of gut ischemia prior to development of NEC.

There are several possible explanations for transfusion-associated NEC. This patient's clinical presentation and NIRS data suggest that the interplay of hypoxemic mucosal gut injury associated with anemia followed by increased splanchnic oxygenation seen with transfusion could lead to reperfusion injury and an inflammatory cascade ultimately leading to bowel necrosis and NEC.10 These series of events may play a role in the predisposition of very low birth-weight infants to develop NEC in the interval following a transfusion.

A similar case report of NIRS results in an infant who developed posttransfusion NEC was published by Marin and Moore25 in this journal. The neonate in that report had gram-negative bacteremia, and required mechanical ventilation at the time of RBC transfusion, while the neonate in our report was clinically stable on nasal cannula without signs of sepsis at initiation of transfusion. Another difference between these 2 case reports was that splanchnic rSO2 dramatically decreased during the RBC transfusion in Marin's report while our patient's splanchnic rSO2 increased as expected during the transfusion and then precipitously decreased 3 to 6 hours posttransfusion. While there are differences in the patient characteristics and NIRS results, both reports demonstrate the ability of NIRS to detect changes in splanchnic oxygenation prior to the development of clinical symptoms of NEC.

In summary, we propose that NIRS could be a valuable tool for the bedside nurse to help identify neonates at risk for developing NEC following RBC transfusions as well as any other clinical conditions that may impair splanchnic oxygenation such as a hemodynamically significant PDA. For instance, if a decrease in splanchnic rSO2 is observed following a transfusion, the bedside nurse could alert the rest of the team and the patient could be kept nothing by mouth for a longer period, or feedings could be reinitiated with more caution.

Considering the well-known limitations of a case report, we have continued screening and entering further patients into our observational study to determine the clinical utility of NIRS monitoring during the peritransfusion period in neonates at risk for NEC.

-
What we know:
  • NEC is the most common gastrointestinal emergency encountered in the newborn intensive care unit and represents a significant cause of morbidity and mortality in premature infants.

  • Sequence of events leading to NEC appears to be multifactorial and complex, but other than prematurity no single predictive risk factor has been clearly delineated.

  • A significant association between elective RBC transfusion and the subsequent development of NEC has been consistently observed in premature infants.

  • NIRS is a noninvasive bedside technology that allows for real-time determination of rSO2 in body tissues such as the brain and mesentery and has the potential to detect actual tissue bed ischemia.

What needs to be studied:
  • Determine whether NIRS rSO2 is truly reflective of the balance between tissue oxygen supply and demand, which can be altered by neonatal pathologies such as NEC and anemia.

  • Determine whether NIRS can become a tool for the bedside nurse to help identify neonates at risk for developing NEC following RBC transfusions as well as any other clinical conditions that may impair splanchnic oxygenation such as a hemodynamically significant PDA.

What can we do today:
  • In NICUs that already utilize NIRS technology for cerebral and renal regional oxygenation monitoring, introduce the use of splanchnic regional oxygenation.

  • When implementing NIRS technology into routine NICU practice, education is key to recognize, understand, and appropriately interpret changes of abnormal NIRS trends.

  • Develop awareness of the increased risk for NEC in premature infants with significant anemia that receive packed RBC transfusions.


References

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Keywords:

near-infrared spectroscopy; necrotizing enterocolitis; preterm neonate; red blood cell transfusion

© 2020 by the National Association of Neonatal Nurses.