Single-center retrospective study finds volume-linked PPV changes after pediatric craniosynostosis repair boluses

Blood-product boluses during pediatric craniosynostosis repair were associated with reductions in pulse pressure variation that increased with bolus volume, while mean arterial pressure rose by a similar amount regardless of volume, according to a retrospective study at Seattle Children’s Hospital. The analysis included 798 bolus events in 111 children and does not establish that PPV-guided treatment improves clinical outcomes.

The study examined children who underwent open cranial vault expansion at the hospital from January 2021 through December 2024. Included patients were 1 to 23 months old, with a mean age of 10 months and a standard deviation of 4.6 months. The researchers analyzed electronic anesthetic records for packed red blood cells and fresh frozen plasma, mean arterial pressure, pulse pressure variation and bolus timing and volume. A PPV value is a dynamic variable reflecting changes in arterial pulse pressure during mechanical ventilation.

Of 188 craniosynostosis repair cases in patients younger than two years, 17 were excluded because no packed red blood cells or fresh frozen plasma were administered or because a platelet transfusion for pre-existing thrombocytopenia was documented instead of volume resuscitation. Most of the cases without blood-product administration involved endoscopic repair of sagittal craniosynostosis, which the paper notes is associated with substantially less blood loss. The final analysis contained 798 bolus events from 111 patients.

Discrete transfusions documented at the same time were treated as one combined bolus, while multiple transfusions within a 10-minute interval were aggregated and analyzed using the start of the first and end of the last bolus. Combined boluses exceeding 200 mL and individual boluses exceeding that amount were excluded because the authors considered the larger entries likely to reflect inaccurate temporal documentation. Pre-bolus and post-bolus mean arterial pressure and PPV were calculated from values recorded during the five minutes before and after each bolus.

The investigators used a linear mixed-effects model with pre- versus post-bolus time, weight-based bolus volume and their interaction as fixed effects. Patient and bolus event nested within patient were modeled as random effects to account for repeated observations. The model estimated that a blood-product bolus was associated with a 1.60 mmHg increase in mean arterial pressure, with a 95% confidence interval of 1.14 to 2.06, and a 0.82-percentage-point reduction in PPV, with a 95% confidence interval of 0.59 to 1.06. Both associations had p-values below 0.001.

PPV showed an additional association with the volume transfused. The full results reported that each additional 1 mL/kg of blood product was associated with a further 0.04-percentage-point decrease in post-bolus PPV, with a 95% confidence interval of 0.02 to 0.07 and p=0.002. By contrast, the increase in mean arterial pressure did not vary with bolus volume; the interaction p-value was 0.918. The analysis therefore found a dose-dependent association for PPV but not for mean arterial pressure.

The absolute changes were modest: approximately 1.6 mmHg for mean arterial pressure and 0.82 percentage points for PPV after a bolus. The authors noted that retrospective charting practices could obscure relationships between transfusions and physiological responses. Their model did not account for differences among providers, the method of administering blood products, or the PPV thresholds used to trigger transfusion. Aggregating transfusions over short intervals could also introduce noise, while anesthetic depth, continuing blood loss, vasoactive medications, calcium administration and possible venous air embolism could influence hemodynamic measurements.

Other unmeasured factors included ventilation mode, tidal volume, positive end-expiratory pressure and patient positioning. Although controlled ventilation, relatively generous tidal volumes and a positive end-expiratory pressure of 5 cmH2O were common at the institution, these settings were not incorporated into the model. The researchers also noted that the study included no analysis of PPV during periods without blood-product administration, which they said would strengthen causal inference.

The findings are limited by their retrospective, single-center design and the specific population undergoing open cranial vault expansion. They support an association between transfused blood-product volume and subsequent PPV in these surgical cases, but they do not demonstrate that PPV is a validated predictor of fluid responsiveness in pediatric patients generally. The authors called for prospective and multicenter research, including prospective validation, more detailed analysis of bolus timing and composition, examination of ventilation and positioning, and evaluation of possible PPV thresholds for resuscitation.

Subject of Research: Associations between blood-product bolus volume, pulse pressure variation and mean arterial pressure during pediatric craniosynostosis repair

Article Title: Pulse pressure variation demonstrates dose-dependent response to volume resuscitation in pediatric craniosynostosis repair

Article References: Yao, P. Y., Fontenot, M. R., Quinlan, C. A., & O’Reilly-Shah, V. N. (2026). Pulse pressure variation demonstrates dose-dependent response to volume resuscitation in pediatric craniosynostosis repair. PLOS One, 21(10), e0360509. https://doi.org/10.1371/journal.pone.0360509

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0360509

Keywords: pediatric craniosynostosis, pulse pressure variation, volume resuscitation, blood-product transfusion, mean arterial pressure, retrospective cohort study, pediatric surgery, hemodynamic monitoring, Pulse, pressure, variation, demonstrates