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Effect of Phytonadione on Correction of Coagulopathy in Pediatric Patients With Septic Shock
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Design
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Retrospective, single-center, observational study
= 156
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Objective
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To evaluate phytonadione in children with septic shock with disseminated intravascular coagulopathy (DIC)
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Study Groups
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No follow-up INR (n= 10)
Follow-up INR ≤1.2 (n= 66)
Follow-up INR >1.2 (n= 80)
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Inclusion Criteria
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Children aged <18 years; admitted to a pediatric intensive care unit or cardiac intensive care unit; diagnosis of septic shock; received IV phytonadione |
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Exclusion Criteria
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Patients who received phytonadione via oral, intramuscular, or subcutaneous route; received warfarin; received chronic phytonadione (including with total parenteral nutrition) prior to coagulopathy; had chronic liver or hematologic disease |
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Methods
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This was a retrospective chart review of children admitted to the pediatric intensive care unit or cardiac intensive care unit at a single tertiary care academic center in Oklahoma. There was no standardized dosing protocol for phytonadione for sepsis-induced DIC.
Patients had an INR collected within 24 hours prior to IV phytonadione, during therapy, and up to 24 hours post-administration. When multiple INRs were collected, the closest value to 24 hours post-dose was used for this analysis. For patients who received more than 1 course of phytonadione for septic shock during the study period, only their initial course was included.
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Duration
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October 1, 2013 to August 31, 2020
Follow-up: up to 24 hours post-phytonadione
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Outcome Measures
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Primary: number of patients who achieved a normalized INR (defined as an INR ≤1.2)
Secondary: INR change, phytonadione dosing regimens
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Baseline Characteristics
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No follow-up INR (n= 10)
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Follow-up INR ≤1.2 (n= 66)
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Follow-up INR >1.2 (n= 80)
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p-value |
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Age, years (IQR)
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9.4 (0.93–14.6) |
5.33 (0.92–11.5) |
3.56 (0.38–12.7) |
0.45 |
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Male
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50% |
51.5% |
60% |
0.30 |
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Weight, kg (IQR)
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31.9 (6.82–58.3) |
17.5 (8–41.8) |
14.15 (4.8–37.4) |
0.28 |
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PRISM III score (IQR)
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12.5 (4.25–19.5) |
11 (7-19) |
15 (6-23) |
0.26 |
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Active bleeding
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0 |
12.1% |
5% |
0.12 |
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Medications
Anticoagulation*
Vasopressors
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10%
50%
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3%
57.6%
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8.8%
71.3%
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0.18
0.08
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ECMO
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0 |
4.5% |
3.8% |
1.0 |
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Mortality
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20% |
7.6% |
1.3% |
0.22 |
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ECMO: extracorporeal membrane oxygenation; IQR: interquartile range; PRISM III: Pediatric Risk of Mortality III
*enoxaparin or heparin
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Results
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Endpoint
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No follow-up INR (n= 10)
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Follow-up INR ≤1.2 (n= 66)
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Follow-up INR >1.2 (n= 80)
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p-value
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Total number of phytonadione doses (IQR)
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2 (1-3) |
3 (2-3) |
3 (2-3) |
0.58 |
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Phytonadione dosage
Initial dose, mg
Initial dose, mg/kg
Cumulative dose, mg
Cumulative dose, mg/kg
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2.8 (1.3–5.0)
0.15 (0.09–0.30)
6.75 (3.00–10.00)
0.19 (0.12–0.57)
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1.0 (1.0–5.0)
0.12 (0.05–0.23)
3.00 (2.50–10.00)
0.27 (0.12–0.60)
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1.0 (1.0–2.75)
0.13 (0.05–0.26)
3.00 (2.00–8.50)
0.30 (0.11–0.79)
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0.56
0.50
0.60
0.47
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Received blood products
Fresh frozen plasma
Cryoprecipitate
Both
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50%
0
0
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42.4%
15.2%
10.6%
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62.5%
12.3%
11.3%
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0.02
0.65
0.90
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Only 42.3% of pediatric patients achieved a normalized INR following phytonadione therapy.
Overall, 55.8% of patients received either fresh frozen plasma or cryoprecipitate in addition to phytonadione for sepsis-induced coagulopathy; 10.3% received both. Two additional patients received prothrombin complex concentrate in addition to blood products.
There was a significantly higher median (IQR) baseline INR in patients who received cryoprecipitate and/or fresh frozen plasma with phytonadione versus phytonadione alone (1.9 [IQR, 1.6–2.5] vs 1.7 [IQR, 1.5–2.0]; p= 0.03). There was no significant difference in cumulative phytonadione dose, but patients who received blood products received more doses of phytonadione than patients who received phytonadione alone (p= 0.005).
The overall mean change in INR from baseline with each phytonadione dose ranged from −0.18 to −0.55, with the largest reduction seen after the 2nd dose.
Per a logistic regression analysis, baseline INR, fresh frozen plasma, cryoprecipitate, vasopressors, PRISM III score, or cumulative phytonadione dose were not associated with achieving a normalized INR.
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Adverse Events
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Not evaluated
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Study Author Conclusions
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Less than half of patients achieved a normalized INR. The median cumulative dose of phytonadione and receipt of FFP or cryoprecipitate was not associated with an increased odds of a normalized INR. Future studies are needed to further explore phytonadione use in children with sepsis-induced coagulopathy. |
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InpharmD Researcher Critique
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Limitations of this study include the small sample size and single-center aspect. Additionally, 10 courses had no follow-up INR reported. The retrospective nature of the study also allows for reporting errors and confounding variables. Adverse events were not collected due to difficulties in differentiating documentation of active bleeding or adverse events attributed to phytonadione.
No dosing protocol was used, which also may have varied the results. However, a logistic regression model found cumulative phytonadione dose was not associated with a normalized INR. Similarly, the timing of INR after phytonadione administration was not uniform.
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