Abstract
OBJECTIVE
To evaluate safety and clinical benefit of sodium acetate umbilical arterial catheter (UAC) fluid in neonates.
METHODS
This single-center, retrospective cohort study included neonates receiving dextrose 5% or sodium acetate 77 mEq/L heparinized fluid for UAC patency. The primary outcome was the potential number of capillary heel sticks avoided. Secondary outcomes included hypernatremia, intraventricular hemorrhage, metabolic acidosis, acute kidney injury, chronic lung disease, and parenteral nutrition optimization. Subgroup analysis was performed for patients undergoing therapeutic hypothermia and preterm infants.
RESULTS
There were 202 patients (dextrose n = 100; sodium acetate n = 102) included. The sodium acetate group demonstrated a greater number of potential heel sticks avoided per UAC line day (0 vs 2.2; p < 0.001). Despite a higher incidence of hypernatremia (sodium > 145 mEq/L) with sodium acetate, hypernatremia with sodium > 150 mEq/L were not significant between groups and there were no significant differences in other clinical outcomes.
CONCLUSIONS
Using sodium acetate for UAC patency is safe and may decrease the number of painful capillary heel sticks.
Keywords: hemorrhage, hypernatremia, infant, newborn, infant, premature, sodium acetate
Introduction
An umbilical arterial catheter (UAC) allows for arterial blood sampling for labs and accurate measurements of systemic arterial blood pressure. In the neonatal intensive care unit (NICU), placement of a UAC is indicated for infants who require frequent arterial blood gas or blood pressure monitoring. Examples of neonatal patients requiring frequent laboratory monitoring include premature infants weighing < 1.5 kg, infants undergoing treatment with therapeutic hypothermia, and patients with hypo- or hyperglycemia.1
Dextrose 5% has been utilized for patency of the UAC due to concerns with sodium administration causing intraventricular hemorrhage or delaying postnatal diuresis in the first few days of life. However, using dextrose as the UAC patency fluid may confound blood glucose laboratory values drawn off the same arterial line. As 5% dextrose has a glucose concentration of 5000 mg/dL, even minimal sample contamination will produce falsely high blood glucose concentrations. Due to previous reports of serious harm from clinicians treating falsely elevated blood glucose values from utilizing dextrose arterial fluids, the practice is to confirm the blood glucose value from the arterial line to a capillary heel stick.2 Pineles et al3 reported that preterm infants are sensitive to heel stick induced pain, with significant increases in heart rate and behavioral agitation during a heel stick compared to baseline. Notably, the heart rate and behavioral agitation responses have been shown to significantly increase with each additional heel stick, indicating greater pain with subsequent procedures.3 Other adverse effects that have been reported with heel sticks are bruising caused by excessive or prolonged squeezing, local infection at the puncture site, ischemic necrosis of the foot skin, calcaneal osteomyelitis, and calcified nodules on the heel induced by repeated heel sticks.4 Unlike dextrose, sodium-based fluids do not confound blood glucose results and would not require a confirmatory heel stick for arterial blood glucose values. Utilizing sodium-based fluids as an alternative to dextrose may decrease the number of painful capillary heel sticks infants experience.
Additionally, premature neonates are born with renal tubular immaturity, which causes an increased urinary bicarbonate loss and reduced capacity to excrete ammonium. This leads to an increased risk of a transient anion gap metabolic acidosis, which can be exacerbated by exogenous administration of chloride from sodium chloride boluses, fluids, flushes, and sodium chloride-containing medications.5–7 The use of sodium acetate as an alternative to decrease overall chloride intake may therefore reduce the incidence of hyperchloremia, metabolic acidosis, and acute kidney injury. In addition, by providing early initiation of acetate from an alternative source outside of total parenteral nutrition (TPN), this practice change may allow for earlier addition of phosphorus (sodium phosphate or potassium phosphate) into TPN to optimize bone development and mineralization.8–11
Hassenfeld Children’s Hospital at NYU Langone Health, a large academic medical center, underwent a practice change in October 2021 from using dextrose 5% to sodium acetate 77 mEq/L as the standard fluid for UAC patency. This practice change was made in effort to decrease the number of painful capillary heel sticks neonates experience based on the above evidence. The purpose of this study is to evaluate the impact of using sodium acetate as the primary UAC fluid on frequency of heel sticks and clinical outcomes.
Methods
This is a single-center retrospective cohort study at NYU Langone Hassenfeld Children’s Hospital between January 1, 2018 and June 30, 2023. All infants admitted to the NICU with a UAC who received either dextrose 5% or sodium acetate 77 mEq/L heparinized fluid for patency were included. Patients requiring extracorporeal membrane oxygenation, receiving UAC fluids at a rate of > 1 mL/hr, or who were transferred out of the NICU within the first week of life were excluded.
Hassenfeld Children’s Hospital implemented a new neonatal arterial line guideline in 2021 to change the preferred UAC patency fluid from dextrose 5% to sodium acetate 77 mEq/L. Medication records and NICU admission order sets in the electronic health record were modified to reflect this practice change. The neonatal arterial line institutional guideline was updated with the new fluid recommendations and verbiage instructing nurses to obtain serum glucose concentrations via the UAC if running a sodium-based fluid or via heel stick if running a dextrose-based fluid. Nursing and provider education was provided daily during morning safety huddles to reinforce concepts with this practice change. A 3-month washout period after practice change implementation was incorporated within the study design to account for this transitional period. In addition, in efforts to decrease the potential risk of hypernatremia with this practice change, the ampicillin diluent was switched from normal saline to sterile water and sodium acetate 77 mEq/L flushes were utilized instead of normal saline flushes in patients < 30 weeks gestation for the first week of life.
To provide context on our institutional practice for parenteral nutrition initiation, custom parenteral nutrition bags are started on preterm infants, late preterm infants if anticipated to remain NPO after 24 to 48 hours of life, full term infants if expected to remain NPO after 48 to 72 hours of life, and for all other patients unable to tolerate enteral feedings to sustain growth within a reasonable amount of time. The guidance for the infant’s first day of life is to initiate dextrose containing fluids or starter TPN depending on the age of the patient to target a glucose infusion rate of 4 to 6 mg/kg/min. Notable electrolyte starting doses are sodium 1 mEq/kg, potassium 1 mEq/kg, and phosphorus 1 to 1.5 mmol/kg in preterm infants with central access with calcium ordered in a 1:1 ratio with phosphorus. Subsequent custom parenteral nutrition bags are advanced and titrated based on patient-specific laboratory results.
Data was obtained through a retrospective electronic health record review for baseline demographics and medical treatments received, such as therapeutic hypothermia. Additional data points collected included mode of delivery, Score for Neonatal Acute Physiology with Perinatal Extension (SNAPPE-II), number of days with the UAC line, UAC fluid rate, and total intake of electrolytes (sodium, chloride, and acetate) from TPN and electrolyte-containing fluid bags.
The primary objective of this study was to evaluate the potential number of capillary heel sticks avoided per line day for each patient with a UAC. The documentation of point-of-care glucose testing was used as a surrogate marker for the number of capillary heel sticks patients in the dextrose group received. For the sodium acetate group, the point-of-care glucose test result was presumed to be drawn off the UAC line without a capillary heel stick based on verbiage in unit guidelines. Secondary outcomes included the incidence of hypernatremia, intraventricular hemorrhage, metabolic acidosis, acute kidney injury, chronic lung disease (CLD), and day of life phosphate was added to TPN. Acute kidney injury was defined as an increase in serum creatinine by at least 2 times the baseline serum creatinine. Chronic lung disease was defined as patients born < 32 weeks gestational age (GA) still requiring respiratory support for ≥ 28 days and are on some respiratory support at 36 weeks post-menstrual age. A subgroup analysis was performed to evaluate outcomes for patients undergoing therapeutic hypothermia and preterm patients < 28 weeks GA and 28 to 32 weeks GA.
Patients who received dextrose were categorized as “pre-practice change” and those who received sodium acetate were categorized as “post-practice change.” Demographic data are reported to characterize the total cohort and compare the pre-practice change and post-practice change cohorts. Categorical variables are reported as n (%) and continuous variables are reported as median (IQR). χ2 test and Fisher exact test were used for categorical variables. Mann-Whitney U test was used for continuous variables. A p-value < 0.05 was considered statistically significant. All data were securely stored in RedCap database, and statistics were conducted using IBM SPSS Statistics for Windows, version 27 (IBM Corp, Armonk, NY).
Results
Screening, Baseline Characteristics, and UAC Fluid Characteristics.
A total of 318 infants admitted to the NICU were screened. After excluding 6 patients who required extracorporeal membrane oxygenation, 8 patients with a UAC fluid rate > 1 mL/hr, and 102 infants who were transferred out of the NICU within the first week of life, 202 patients were included (dextrose n = 100, 49.5%; sodium acetate n = 102, 50.5%) (Figure). The median gestational age was 30.2 weeks (IQR 27.5–37.4) and 58% of patients were male. 62.4% of neonates were delivered via Cesarean section and the median SNAPPE-II score was 25.5 (16.0–37.3). The median number of days with a UAC line was 3.1 (1.9–4.4) and the majority of patients received UAC fluids at 1 mL/hr (86.1%). When comparing the total electrolyte intake from all sources of UAC fluids, electrolyte-containing fluid bags, and TPN, compared with the dextrose group, patients in the sodium acetate group received more sodium per UAC line day (0.4 mEq/kg/day [0–0.8] vs 1.0 mEq/kg/day [0.3–1.7]; p < 0.001) and acetate per UAC line day (0.2 mEq/kg/day [0–0.5] vs 0.8 [0.5–1.3]; p < 0.001). There were no significant differences between groups in chloride intake from UAC fluids, electrolyte-containing fluid bags, and TPN. Outside of the UAC fluids, there was no significant difference between groups in the electrolyte contents of electrolyte-containing intravenous solutions and TPN contents (Table 1).
Figure.
Patient enrollment.
Table 1.
Infant Characteristics
| Characteristic | Total Cohort N = 202 |
Dextrose N = 100 |
Sodium Acetate N = 102 |
p value |
|---|---|---|---|---|
| Male, n (%) | 118 (58.4) | 61 (61.0) | 57 (55.9) | 0.461 |
| Gestational age, median (IQR) | 30.2 (27.6–37.4) | 31.0 (27.7–37.7) | 29.8 (27.0–36.6) | 0.134 |
| GA 22–28, n (%) | 63 (31.2) | 27 (27.0) | 36 (35.3) | 0.203 |
| GA 28–32, n (%) | 57 (28.2) | 27 (27.0) | 30 (29.4) | 0.703 |
| GA 32–37, n (%) | 26 (12.9) | 14 (14.0) | 12 (11.8) | 0.635 |
| > 37 wk, n (%) | 56 (27.7) | 32 (32.0) | 24 (23.5) | 0.179 |
| Mode of delivery | ||||
| Cesarean, n (%) | 126 (62.4) | 60 (60.0) | 66 (64.7) | 0.490 |
| SNAPPE-II score, median (IQR) | 25.5 (16.0–37.3) | 22.0 (16.0–36.5) | 26.0 (16.0–38.3) | 0.300 |
| Therapeutic hypothermia treatment, n (%) | 22 (10.9) | 9 (9.0) | 13 (12.7) | 0.393 |
| Number of days with UAC line, median (IQR) | 3.1 (1.9–4.4) | 3.5 (1.9–4.7) | 3.0 (1.8–4.4) | 0.444 |
| UAC fluid rate | 0.048 | |||
| 0.5 mL/hr, n (%) | 28 (13.9) | 9 (9.0) | 19 (18.6) | 0.048 |
| 1 mL/hr, n (%) | 174 (86.1) | 91 (91.0) | 83 (81.4) | 0.048 |
| Total electrolytes from UAC fluids, electrolyte-containing fluid bags, and TPN | ||||
| Sodium, mEq/kg/day (IQR) | 0.8 (0.3–1.3) | 0.4 (0–0.8) | 1.0 (0.7–1.7) | < 0.001 |
| Chloride, mEq/kg/day (IQR) | 0.2 (0–0.8) | 0.03 (0–0.6) | 0.3 (0–0.9) | 0.205 |
| Acetate, mEq/kg/day (IQR) | 0.5 (0.1–1.0) | 0.2 (0–0.5) | 0.8 (0.5–1.3) | < 0.001 |
| Total electrolytes from electrolyte-containing fluid bags + TPN (excluding UAC fluids) | ||||
| Sodium, mEq/kg/day (IQR) | 1.0 (0.0–3.0) | 1.0 (0.0–3.0) | 1.0 (0.0–3.2) | 0.542 |
| Chloride, mEq/kg/day (IQR) | 0.6 (0.0–3.1) | 0.1 (0.0–2.8) | 1.0 (0.0–3.6) | 0.266 |
| Acetate, mEq/kg/day (IQR) | 0.6 (0.0–1.8) | 0.6 (0.0–2.2) | 0.6 (0.0–1.7) | 0.759 |
GA, gestational age; SNAPPE-II, Score for Neonatal Acute Physiology with Perinatal Extension; TPN, total parenteral nutrition; UAC, umbilical arterial catheter
Primary and Secondary Outcomes.
Patients in the sodium acetate group had a lower number of total glucose checks compared to dextrose (8.0 [4.0–16.3] vs 6.0 [2.0–14.0]; p = 0.012). The number of confirmatory glucose checks per UAC line day was significantly higher in the dextrose group (2.7 [1.7–4.0] vs 0 [0–0]; p < 0.001). There was a significantly greater number of potential heel sticks avoided per UAC line day in the sodium acetate group (0 vs 2.2 [1.0–4.0]; p < 0.001) (Table 2).
Table 2.
Results – Full Cohort
| Outcome | Total Cohort N = 202 |
Dextrose N = 100 |
Sodium Acetate N = 102 |
p value |
|---|---|---|---|---|
| Total number of glucose checks per patient, median (IQR)* | 6.0 (3.0–14.0) | 8.0 (4.0–16.3) | 6.0 (2.0–14.0) | 0.012 |
| Potential number of confirmatory glucose checks per UAC line day, median (IQR) | 2.5 (1.4–4.0) | 2.7 (1.7–4.0) | 0.0 (0–0) | < 0.001 |
| Potential number of heel sticks avoided per UAC line day, median (IQR) | 0.0 (0–2.7) | 0.0 (0–0) | 2.2 (1.0–4.0) | < 0.001 |
| Hypernatremia (sodium > 145 mEq/L), n (%) | 42 (20.8) | 13 (13) | 29 (28.4) | 0.007 |
| Sodium > 150 mEq/L, n | 10 | 5 | 5 | 0.238 |
| Hypernatremia Intervention | ||||
| Switched back to D5%, n | 4 | 0 | 4 | 0.293 |
| Increased total fluid rate, n | 29 | 9 | 20 | 0.986 |
| Discontinue umbilical arterial line fluids, n | 3 | 0 | 3 | 0.540 |
| No intervention, n | 7 | 4 | 3 | 0.176 |
| Intraventricular hemorrhage, n (%) | 45 (22.3) | 23 (23.0) | 22 (21.6) | 0.807 |
| Grade 1–2, n | 42 | 21 | 21 | 0.943 |
| Grade 3–4, n | 3 | 2 | 1 | 0.619 |
| Metabolic acidosis, n (%) | 98 (48.5) | 53 (53.0) | 45 (44.1) | 0.207 |
| Received sodium bicarbonate, n | 3 | 2 | 1 | 0.619 |
| Acute kidney injury, n (%) | 2 (1.0) | 1 (1.0) | 1 (1.0) | 1.000 |
| Chronic lung disease, n (%) | 74 (37) | 33 (33) | 41 (40) | 0.289 |
| Mild, n† | 15 | 8 | 7 | 0.446 |
| Moderate, n‡ | 50 | 19 | 31 | 0.100 |
| Severe, n§ | 9 | 6 | 3 | 0.155 |
| TPN, n (%) | 196 (97) | 99 (99) | 97 (95) | 0.212 |
| Day of life TPN started, median (IQR) | 0 (0–1) | 0 (0–1) | 0 (0–0) | 0.061 |
| Day of life phosphate added to TPN, median (IQR) | 1 (1–2) | 2 (1–2) | 1 (1–2) | < 0.001 |
CLD, chronic lung disease; TPN, total parenteral nutrition; UAC, umbilical arterial catheter
* The number reported for dextrose group is all heel sticks.
† Mild CLD: requiring 2L nasal cannula (NC) or less.
‡ Moderate CLD: requiring > 2L NC of non-invasive support (Vapotherm > 2L, continuous positive airway pressure, synchronized inspiratory positive airway pressure, or non-invasive positive pressure ventilation).
§ Severe CLD: intubated and requiring mechanical ventilation.
For secondary outcomes, there was a higher incidence of hypernatremia (sodium > 145 mEq/L) in the sodium acetate group (13 [13%] vs 29 [28.4%]; p = 0.007). Among patients who experienced hypernatremia, there was no significant difference between groups in clinically significant hypernatremia, defined as serum sodium > 150 mEq/L (5 vs 5; p = 0.238). The primary intervention for patients in both groups who experienced hypernatremia was an increase in total fluid rate. Four patients in the sodium acetate group were switched back to dextrose 5% UAC fluids due to hypernatremia. There was no significant difference between the 2 groups in incidence or severity of intraventricular hemorrhage, metabolic acidosis, acute kidney injury, CLD of any severity, or day of life TPN started. Out of the 196 infants who received TPN, the majority initiated TPN on day of life 1 (142/196, 72.4%). Infants in the sodium acetate group were able to start phosphate in TPN 1 day earlier (p < 0.001) (Table 2).
Subgroup Analysis.
The subgroup analysis revealed consistent findings with a significant reduction in the potential number of confirmatory glucose checks and heel sticks avoided across all selected subgroups. There was no statistically significant variance observed in the total number of glucose checks per patient within the subgroups. Within the preterm population of patients < 32 weeks GA, there was a modest numerical decrease in total glucose checks in the sodium acetate group (extremely preterm patients < 28 weeks GA: 12.0 [6.0–14.0] vs 6.0 [3.3–14.8]; p = 0.106; very preterm patients between 28–32 weeks GA: 6.0 [3.0–10.0] vs 4.5 [2.0–7.5]; p = 0.146).
For secondary outcomes, extremely preterm infants < 28 weeks GA receiving sodium acetate experienced a higher incidence of hypernatremia (4 [14.8%] vs 17 [47.2%]; p = 0.007). Among the extremely preterm infants, there was no difference in the overall incidence of CLD (19 [70%] vs 25 [69%]; p = 0.937); however, patients who received sodium acetate had a higher incidence of moderate severity CLD (10 vs 21; p = 0.024). The majority continued sodium acetate with an increased fluid rate (13 [76.5%]) and 2 patients were switched to dextrose UAC fluids. Within the very preterm group (28–32 weeks GA), patients receiving dextrose experienced a higher incidence of metabolic acidosis (16 [59.3%] vs 8 [26.7%]; p = 0.013). Very preterm infants receiving sodium acetate were able to start phosphate in their TPN 1 day earlier than the dextrose group. There were no significant differences in secondary outcomes within the therapeutic hypothermia subgroup, however patients undergoing therapeutic hypothermia underwent the highest number of glucose checks among all subgroups (17 [14–22] vs 17 [11–21]; p = 0.647) (Tables 3 and 4).
Table 3.
Results – Extremely Preterm and Very Preterm Infants
| Extremely Preterm (< 28 wk) | |||
|---|---|---|---|
| Outcome | Dextrose N = 27 |
Sodium Acetate N = 36 |
p value |
| Total number of glucose checks per patient, median (IQR)* | 12.0 (6.0–14.0) | 6.0 (3.3–14.8) | 0.106 |
| Potential number of confirmatory glucose checks per UAC line day, median (IQR) | 2.9 (2.1–3.7) | 0.0 (0.0–0.0) | < 0.001 |
| Potential number of heel sticks avoided per UAC line day, median (IQR) | 0.0 (0.0–0.0) | 1.9 (1.0–4.5) | < 0.001 |
| Hypernatremia, n (%) | 4 (14.8) | 17 (47.2) | 0.007 |
| Sodium > 150, n | 2 | 5 | 0.574 |
| Hypernatremia intervention | |||
| Switched back to D5%, n | 0 | 2 | 1.000 |
| Increased total fluid rate, n | 3 | 13 | 1.000 |
| Discontinue umbilical arterial line fluids, n | 0 | 0 | — |
| No intervention, n | 1 | 2 | 0.489 |
| Intraventricular hemorrhage, n (%) | 11 (40.7) | 10 (27.8) | 0.280 |
| Grade 1–2, n | 10 | 9 | 0.303 |
| Grade 3–4, n | 1 | 1 | 1.000 |
| Metabolic acidosis, n (%) | 19 (70.4) | 18 (50.0) | 0.104 |
| Received sodium bicarbonate, n | 0 | 0 | — |
| Acute kidney injury, n (%) | 0 (0) | 1 (2.8) | 1.000 |
| Chronic lung disease, n (%) | 19 (70) | 25 (69) | 0.937 |
| Mild, n† | 5 | 2 | 0.210 |
| Moderate, n‡ | 10 | 21 | 0.024 |
| Severe, n§ | 4 | 2 | 0.378 |
| TPN, n (%) | 27 (100) | 36 (100) | — |
| Day of life TPN started, median (IQR) | 0.0 (0–0) | 0.0 (0–0) | 0.397 |
| Day of life phosphate added to TPN, median (IQR) | 2.0 (1.0–2.0) | 1.0 (1.0–2.0) | 0.093 |
| Very Preterm (28–32 wk) | |||
| Outcome |
Dextrose
N = 27 |
Sodium Acetate
N = 30 |
p value |
| Total number of glucose checks per patient, median (IQR)* | 6.0 (3.0–10.0) | 4.5 (2.0–7.5) | 0.146 |
| Potential number of confirmatory glucose checks per UAC line day, median (IQR) | 2.5 (1.5–4.8) | 0.0 (0.0–0.0) | < 0.001 |
| Potential number of heel sticks avoided per UAC line day, median (IQR) | 0.0 (0.0–0.0) | 2.5 (1.3–4.1) | < 0.001 |
| Hypernatremia, n (%) | 3 (11.1) | 6 (20.0) | 0.476 |
| Sodium > 150, n | 2 | 0 | 0.083 |
| Hypernatremia intervention | |||
| Switched back to D5%, n | 0 | 1 | 1.000 |
| Increased total fluid rate, n | 2 | 3 | 1.000 |
| Discontinue umbilical arterial line fluids, n | 0 | 1 | 1.000 |
| No intervention, n | 1 | 1 | 1.000 |
| Intraventricular hemorrhage, n (%) | 9 (33.3) | 9 (30.0) | 0.787 |
| Grade 1–2, n | 8 | 9 | 0.976 |
| Grade 3–4, n | 1 | 0 | 0.474 |
| Metabolic acidosis, n (%) | 16 (59.3) | 8 (26.7) | 0.013 |
| Received sodium bicarbonate, n | 0 | 0 | — |
| Acute kidney injury, n (%) | 0 | 0 | — |
| Chronic lung disease, n (%) | 14 (52) | 16 (53) | 0.911 |
| Mild, n† | 3 | 5 | 0.689 |
| Moderate, n‡ | 9 | 10 | 0.919 |
| Severe, n§ | 2 | 1 | 0.586 |
| TPN, n (%) | 27 (100) | 30 (100) | — |
| Day of life TPN started, median (IQR) | 0.0 (0–0) | 0.0 (0–0) | 0.292 |
| Day of life phosphate added to TPN, median (IQR) | 2.0 (1.0–2.0) | 1.0 (1.0–1.0) | < 0.001 |
CLD, chronic lung disease; TPN, total parenteral nutrition; UAC, umbilical arterial catheter
* The number reported for dextrose group is all heel sticks.
† Mild CLD: requiring 2L nasal cannula (NC) or less.
‡ Moderate CLD: requiring > 2L NC of non-invasive support (Vapotherm > 2L, continuous positive airway pressure, synchronized inspiratory positive airway pressure, or non-invasive positive pressure ventilation).
§ Severe CLD: intubated and requiring mechanical ventilation.
Table 4.
Results – Therapeutic Hypothermia
| Outcome | Dextrose N = 9 |
Sodium Acetate N = 13 |
p value |
|---|---|---|---|
| Total number of glucose checks per patient, median (IQR)* | 17.0 (13.5–22.0) | 17.0 (11.0–20.5) | 0.647 |
| Potential number of confirmatory glucose checks per UAC line day, median (IQR) | 4.5 (2.9–5.9) | 0.0 (0.0–0.0) | < 0.001 |
| Potential number of heel sticks avoided per UAC line day, median (IQR) | 0.0 (0.0–0.0) | 3.5 (2.4–4.5) | < 0.001 |
| Hypernatremia, n (%) | 3 (33.3) | 6 (46.2) | 0.674 |
| Sodium > 150, n | 1 | 0 | 0.333 |
| Hypernatremia intervention | |||
| Switched back to D5%, n | 0 | 1 | 1.000 |
| Increased total fluid rate, n | 3 | 4 | 0.500 |
| Discontinue umbilical arterial line fluids, n | 0 | 2 | 0.500 |
| No intervention, n | 0 | 0 | — |
| Intraventricular hemorrhage, n (%) | 1 (11.1) | 0 (0.0) | 0.409 |
| Grade 1–2, n | 1 | 0 | 0.409 |
| Grade 3–4, n | 0 | 0 | — |
| Metabolic acidosis, n (%) | 6 (66.7) | 11 (84.6) | 0.323 |
| Received sodium bicarbonate, n | 1 | 1 | 1.000 |
| Acute kidney injury, n (%) | 1 (11.1) | 0 (0.0) | 0.409 |
| TPN, n (%) | 9 (100) | 13 (100) | — |
| Day of life TPN started, median (IQR) | 1.0 (0–1.5) | 1.0 (1.0–1.0) | 0.896 |
| Day of life phosphate added to TPN, median (IQR) | 2.0 (1.0–2.8) | 1.0 (1.0–1.8) | 0.157 |
* The number reported for dextrose group are all heel sticks; TPN, total parenteral nutrition; UAC, umbilical arterial catheter
Discussion
The Pineles et al3 study prompted neonatal providers to pay greater attention to the hemodynamic, physiologic, and developmental effects of repeated painful procedures, including capillary heel sticks. Our study found that utilizing sodium acetate as the primary UAC patency fluid significantly decreased the potential number of capillary heel sticks neonates experience compared to dextrose. The subgroup analyses conducted showed that extremely preterm patients and neonates undergoing therapeutic hypothermia may particularly benefit from this practice change. While there was no significant difference in the total number of blood glucose checks between groups in the therapeutic hypothermia group, the data showed that this subgroup of patients inherently receive more laboratory checks with a median of 17 total heel sticks during UAC placement compared with 8 in the total cohort. By implementing this practice change, neonates may be spared from a significant number of capillary heel sticks from routine confirmatory glucose checks.
While our study showed that there was a higher incidence of hypernatremia in the sodium acetate group, the majority of patients had serum sodium concentration below the clinically significant threshold of 150 mEq/L. Hypernatremia resolved predominantly by increasing the total fluid rate and the majority of patients were able to continue sodium acetate with resolution of hypernatremia. Previous studies have demonstrated an increased odds ratio of severe intraventricular hemorrhage associated with an average sodium intake > 2.5 mEq/kg/day from exogenous administration within the first 4 days of life.8 Despite an increased incidence of hypernatremia in the sodium acetate group, neonates received much less than the recommended maximum of 2.5 mEq/kg/day with a median sodium intake of 1.0 mEq/kg/day. Additionally, there was no significant difference in the incidence or severity of intraventricular hemorrhage between the sodium acetate and dextrose groups. Rates of CLD and acute kidney injury were similar between groups in the total cohort, which may indicate that patients are able to tolerate the adjustment to a higher total volume intake if hypernatremia occurs. The lack of difference in incidence of acute kidney injury may be explained by the similar chloride load of alternative infusions, as patients who received acetate compared to dextrose had no significant difference in the chloride content of TPN or other electrolyte-containing fluids. Of note, within the extremely preterm subgroup, patients who received sodium acetate had a higher incidence of moderate CLD compared to the dextrose group. Although sodium acetate could be a contributing factor, it is more likely that this was an incidental finding due to the small sample size. In addition, key factors influencing the development of CLD, such as duration of intubation and total IV fluid intake, were not assessed in this study.
Furthermore, our study found that patients who received sodium acetate were able to add phosphate into their TPN 1 day earlier compared to patients who received dextrose. While this observation may reflect changes over time in provider practices, it may also highlight recognition that neonates were receiving acetate from the UAC source, prompting them to optimize other TPN components like phosphate. As the majority of bone mineralization occurs in the third trimester, this optimization of phosphorus into the TPN may contribute to preventing osteopenia of prematurity, bone demineralization, and fractures.
Our study has several limitations inherent to its retrospective, single-centered design. Our electronic health record documentation is limited, as laboratory results do not include where the blood sample was obtained. Therefore, the number of heel sticks infants in the dextrose group received was extrapolated from point-of-care glucose values documented, based on our prior institutional NICU practice to confirm blood glucose checks with a capillary heel stick. The point-of-care glucose results for the sodium acetate group were presumed to be collected off the UAC line, without an associated confirmatory heel stick based on the NICU practice change in which nurses were provided daily education to ensure adherence to new policies. In addition, we were unable to collect total fluid intake per day or other sources of exogenous sodium from flushes or medication diluents that may have had an impact on the incidence of hypernatremia. Notably, 2 changes were made to reduce sodium intake at the same time as the UAC fluid practice change. This included 1) changing the ampicillin diluent from normal saline to sterile water and 2) use of sodium acetate 77 mEq/L flushes instead of normal saline flushes in patients < 30 weeks gestation for the first week of life. These changes may have influenced the observed incidence of hypernatremia between the pre- and post-practice change groups. Lastly, we did not assess if increasing the total fluid volume resulted in delayed patent ductus arteriosus closure, although it was reassuring that our results did not show differences in rates of intraventricular hemorrhage or overall CLD between groups.
In conclusion, our study found that using sodium acetate as an alternative UAC fluid is safe and may decrease the number of capillary heel sticks neonatal patients undergo for blood glucose monitoring. While there was an increased incidence of hypernatremia with sodium acetate, there was no significant difference in the clinical outcome of intraventricular hemorrhage. Future prospective studies would be beneficial to confirm the safety of this practice.
ABBREVIATIONS
- CLD
chronic lung disease;
- GA
gestational age;
- NICU
neonatal intensive care unit;
- SNAPPE-II
Score for Neonatal Acute Physiology with Perinatal Extension;
- TPN
total parenteral nutrition;
- UAC
umbilical arterial catheter
Footnotes
Disclosure. The authors declare no conflicts or financial interest in any product or service mentioned in the manuscript, including grants, equipment, medications, employment, gifts, and honoraria. The authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. All authors attest to meeting the four criteria recommended by the ICMJE for authorship of this manuscript.
Ethical Approval and Informed Consent. The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant international guidelines on human experimentation and have been approved by the appropriate committees at our institution, including the international review board. Given the nature of the study informed consent was not required.
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