Cerebral Protection via Transcerebral Gradient-Guided Strategy in Pediatric Bidirectional Glenn

Cerebral Protection via Transcerebral Gradient-Guided Strategy in Pediatric Bidirectional Glenn | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Cerebral Protection via Transcerebral Gradient-Guided Strategy in Pediatric Bidirectional Glenn ibrahim özgür önsel, Barış Kırat, Mustafa Kemal Avşar, Onur Benli, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8624939/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background Off-pump bidirectional Glenn (BDG) avoids cardiopulmonary bypass (CPB), but superior vena cava (SVC) clamping may compromise cerebral perfusion. We evaluated a goal-directed anaesthetic algorithm integrating mean arterial pressure minus SVC pressure (transcerebral gradient, TSG) with cerebral near-infrared spectroscopy (NIRS). Methods We conducted a retrospective two-centre cohort study of 698 children undergoing off-pump BDG (2016–2025). The protocol targeted TSG ≥ 30 mm Hg with continuous invasive arterial and SVC pressure monitoring. Bilateral frontal NIRS was monitored continuously; clinically important desaturation was defined as a ≥ 20% fall from baseline. Stepwise interventions for TSG < 30 mm Hg and/or NIRS desaturation included vasoactive titration, ventilatory optimisation, maintenance of azygos venous drainage during anastomosis, haematocrit optimisation, and temporary autologous venous blood withdrawal with reinfusion after anastomosis. Results There were no deaths (0%, 95% CI 0–0.53%), and all patients were extubated in the operating room. TSG < 30 mm Hg occurred in 89/698 patients (12.8%, 95% CI 10.4–15.5). Cerebral NIRS desaturation occurred in 54/698 (7.7%, 95% CI 5.9–10.0); 9/54 had concomitant TSG < 30 mm Hg. Transient partial seizures occurred in 6/698 (0.86%) within the first 24 h postoperatively, all resolving without sequelae. Mean postoperative pulmonary artery pressure was 11.1 (2.3) mm Hg. Conclusions In this large off-pump BDG cohort, a standardised TSG- and NIRS-guided algorithm was feasible and was associated with low rates of cerebral desaturation and early neurological events. Prospective studies with standardised neurodevelopmental follow-up are warranted. Bidirectional Glenn cerebral oximetry near-infrared spectroscopy off-pump paediatric anaesthesia transcerebral gradient Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Introduction Bidirectional Glenn (BDG) anastomosis is a key second-stage palliation for children with single-ventricle physiology, directing superior vena cava (SVC) flow to the pulmonary arteries (1). Although BDG has traditionally been performed with cardiopulmonary bypass (CPB), many centres now undertake selected cases off-pump to avoid CPB-associated inflammatory activation, coagulopathy and transfusion-related complications, and potential cerebral reperfusion injury—effects that may be amplified in infants and young children (2–4). A specific challenge of the off-pump approach is temporary SVC clamping, which increases SVC pressure, impedes cerebral venous drainage, and may reduce effective cerebral perfusion pressure.5,6 Neurological complications have been reported in approximately 2–5% of off-pump BDG cohorts, underscoring the need for reliable intraoperative surrogates of cerebral perfusion and standardised rescue strategies (3–6). The arterial-to-venous pressure gradient during SVC occlusion—commonly expressed as mean arterial pressure minus SVC/central venous pressure—has been used as a pragmatic haemodynamic surrogate for cerebral perfusion (here termed transcerebral gradient, TSG) (7,8). In parallel, near-infrared spectroscopy (NIRS) provides continuous, non-invasive monitoring of cerebral oxygenation and can detect deteriorating trends before overt clinical signs emerge.9,10 However, published reports rarely describe integrated protocols that combine a prespecified TSG target with NIRS-triggered, stepwise interventions; existing series are typically small and use heterogeneous thresholds and responses (11–13). We hypothesised that a goal-directed algorithm targeting TSG ≥ 30 mm Hg, coupled with NIRS-guided corrective actions during SVC clamping, would reduce clinically important cerebral desaturation and early neurological events during off-pump BDG. We therefore evaluated the feasibility and early outcomes of a standardised TSG–NIRS strategy in 698 consecutive paediatric patients undergoing off-pump BDG at two tertiary centres. Methods Study design and setting This retrospective, observational two-centre cohort study included paediatric patients undergoing off-pump bidirectional Glenn (BDG) anastomosis between 2016 and 2025 at two tertiary cardiac surgery centres. Institutional approval was obtained at both centres, and the study was conducted in accordance with the Declaration of Helsinki. Participants Children aged 4 months to 15 year with single-ventricle physiology scheduled for second-stage palliation after prior systemic-to-pulmonary shunt were eligible. Patients with documented pre-existing neurological sequelae, or a history of previous Glenn or Fontan procedures, were excluded. Patient selection and potential selection bias During the study period, 1,621 BDG procedures were performed; 698 (43.1%) were completed off-pump and 923 (56.9%) were performed with CPB. The present analysis includes the off-pump cohort. Of these, 698 (43.1%) were completed without cardiopulmonary bypass (off-pump BDG) and constitute the study cohort, while 923 (56.9%) were performed with CPB. Off-pump BDG was the default strategy when predefined anatomical and hemodynamic conditions allowed safe superior vena cava (SVC) clamping and cavopulmonary anastomosis without additional major surgical steps. BDG was performed with CPB primarily when concomitant surgical procedures were required or when anatomical complexity was expected to prolong clamp time and reduce the safety margin of an off-pump strategy. In our practice, the most common indications for CPB use were pulmonary artery reconstruction (including patch augmentation/plasty and complex pulmonary artery work) and additional intracardiac/great-vessel procedures such as atrial septectomy, ventricular septal defect (VSD) enlargement, and aortic arch reconstruction. Indications for CPB use were extracted from operative and anesthesia records and are summarized in Table S1. Anaesthesia and haemodynamic monitoring A standardised general anaesthetic protocol was used. Induction included ketamine 2 mg kg⁻¹, fentanyl 2–3 µg kg⁻¹, and midazolam; maintenance consisted of sevoflurane 0.5–1% with propofol infusion 50–100 µg kg⁻¹ min⁻¹ and remifentanil, titrated to clinical effect. Continuous invasive arterial pressure monitoring was obtained via a radial arterial catheter. Central venous (SVC) pressure was measured via an internal jugular or subclavian catheter with the catheter tip positioned in the superior vena cava. Superior vena cava (SVC) pressure was measured via a central venous catheter inserted through the internal jugular or subclavian vein. For continuous and physiologically relevant measurement during SVC clamping, the catheter tip was deliberately kept cranial to (i.e., “above”) the surgical clamp so that the recorded pressure reflected the venous segment draining the head and neck during occlusion. When the planned clamp position would otherwise overlap the catheter tip, the catheter was withdrawn under sterile conditions to maintain the tip cranial to the clamp site. Catheter position was verified by waveform characteristics and intraoperative team confirmation. Transcerebral gradient (TSG) was calculated continuously as mean arterial pressure minus SVC pressure (MAP − SVC). This setup allowed uninterrupted tracking of SVC pressure and TSG evolution before, during, and after clamping across the predefined time points. Transcerebral gradient (TSG) and treatment algorithm TSG was defined as mean arterial pressure minus SVC pressure, and the intraoperative target was TSG ≥ 30 mm Hg during SVC clamping and anastomosis. When TSG fell below 30 mm Hg, norepinephrine 0.05–0.2 µg kg⁻¹ min⁻¹ was initiated and titrated; epinephrine and/or vasopressin were added when required. If targets could not be restored promptly, temporary autologous venous blood withdrawal (3–5 ml kg⁻¹) was performed via the central venous line into sterile collection bags to reduce venous pressure, with reinfusion after completion of the anastomosis. TSG and cerebral rSO₂ were documented at standardized time points on the anesthesia record: T0 (pre-clamp baseline; 1–3-min average immediately before SVC clamping), T1 (1 min after clamping), T2 (worst values during clamping, defined as peak SVC pressure and minimum rSO₂ observed during the clamp period), T4 (2–3 min after completion of the corrective maneuver), and T5 (1 min after clamp release). At each time point, MAP, SVC pressure, calculated TSG (MAP − SVC), and rSO₂ were recorded when applicable. Cerebral NIRS monitoring and stepwise rescue protocol Bilateral frontal cerebral regional oxygen saturation (rSO₂) was monitored continuously using near-infrared spectroscopy (NIRS). Baseline rSO₂ was defined as the average value recorded during a stable pre-clamp period. Clinically important desaturation was defined as a ≥ 20% decrease from baseline. When rSO₂ desaturation and/or TSG < 30 mm Hg occurred, a prespecified stepwise rescue protocol was applied: (i) vasoactive titration to increase arterial pressure, (ii) ventilatory optimisation targeting PaCO₂ 4.7–5.3 kPa (35–40 mm Hg), (iii) maintenance of azygos venous drainage during anastomosis, (iv) haematocrit optimisation (RBC transfusion if haematocrit < 30%), and (v) venous decompression and/or reinfusion according to protocol response. The TSG–NIRS algorithm and intervention sequence were implemented as a shared institutional protocol at both centers. Thresholds (TSG ≥ 30 mmHg; rSO₂ desaturation ≥ 20% from baseline) and the stepwise rescue actions were predefined and identical across sites. Although vasoactive selection and titration were individualized to patient physiology, all interventions were delivered within the same ordered framework (hemodynamic optimization, ventilatory adjustment, hematocrit optimization, maintenance of azygos drainage, and venous decompression when indicated). Center was included as a covariate in regression analyses to account for potential inter-center practice variability. The time point T4 was specifically defined to capture the physiologic response 2–3 minutes after the principal corrective maneuver was implemented. Surgical technique All off-pump BDG procedures in the study cohort were performed through median sternotomy without cardiopulmonary bypass. During SVC clamping, the azygos vein was kept patent to facilitate cerebral venous drainage and was ligated after completion of the anastomosis. Outcomes The prespecified outcomes were: (i) clinically important cerebral NIRS desaturation during SVC clamping, (ii) occurrence of intraoperative TSG < 30 mm Hg, and (iii) early neurological events within the first 24 h after surgery. Seizure events were defined as clinically observed focal seizures documented in the medical record within 24 h postoperatively (with neurology review and additional testing performed according to local practice). TSG < 30, NIRS desat, overlap (n = 9).All patients underwent a standardized immediate postoperative neurological surveillance pathway in the ICU. A focused neurological examination was documented on ICU arrival and at regular intervals during the first 24 h (level of consciousness/behavior, pupillary response, motor symmetry, and presence of abnormal movements). Clinically suspected seizures triggered bedside neurology review and additional testing (e.g., EEG and/or neuroimaging) according to local availability and clinical judgment. Neurological events for this study were defined as clinically observed focal or generalized seizures within 24 h, recorded in the medical chart and adjudicated by ICU and anesthesia teams. Statistical analysis Continuous variables were assessed for distributional assumptions and summarised as mean (SD) or median (IQR), as appropriate; categorical variables were reported as n (%). Group comparisons (TSG < 30 vs ≥ 30 mm Hg) used Student’s t-test or Mann–Whitney U test for continuous variables and χ² test or Fisher’s exact test for categorical variables. A two-sided P value < 0.05 was considered statistically significant. Reporting followed the BJA style for units To explore factors associated with protocol-triggering physiology during SVC clamping, we performed logistic regression analyses for three predefined phenotypes: (i) TSG < 30 mmHg at any time during clamping, (ii) cerebral rSO₂ desaturation ≥ 20% from baseline at any time during clamping, and (iii) the overlap phenotype meeting both criteria. Univariable logistic regression was used to screen candidate predictors (age, weight, ventricular morphology [RV-dominant vs LV-dominant], presence of left SVC, baseline T0 SVC pressure, baseline T0 rSO₂, and center). Multivariable logistic regression models were then constructed for TSG < 30 and for rSO₂ desaturation, including prespecified covariates (age, center) and clinically relevant variables; ventricular morphology was included in the adjusted model for TSG < 30 given its univariable association. Catheterization-derived mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were available in a subset of patients (n = 350) and were evaluated in sensitivity analyses restricted to this subset. Results are reported as odds ratios (OR) or adjusted odds ratios (aOR) with 95% confidence intervals. Results 1,621 BDG procedures performed during the study period, 698 (43.1%) were completed off-pump and 923 (56.9%) were performed with CPB; the present analysis includes the off-pump cohort. Among 698 pediatric patients included, ages ranged from 4 months to 15 years (median: 1.8 years). All patients in the study cohort underwent BDG anastomosis without CPB. Continuous intraoperative monitoring with NIRS and invasive TSG measurement was achieved in all cases. Factors associated with protocol-triggering physiology Univariable analyses of candidate predictors are summarized in Table 1 . RV-dominant ventricular morphology was associated with TSG < 30 mmHg during clamping (OR 1.71, 95% CI 1.07–2.72; p = 0.025). The overlap phenotype (both TSG < 30 and rSO₂ desaturation) occurred in 9 patients (1.3%) and showed exploratory associations with higher weight (OR 1.10 per kg, 95% CI 1.00–1.20; p = 0.044) and the presence of a left SVC (OR 5.17, 95% CI 0.93–28.81; p = 0.061), with wide confidence intervals reflecting low event counts. In multivariable models adjusting for prespecified covariates (Table 2 ), no variable was independently associated with rSO₂ desaturation, whereas ventricular morphology remained independently associated with TSG < 30 (aOR 1.91, 95% CI 1.20–3.04; p = 0.006). Catheterization-derived PAP/PVR were evaluated in the subset with available data (n = 350) as a sensitivity analysis. Table 1 Univariable predictors of protocol-triggering physiology during SVC clamping Predictor (unit) TSG < 30: OR (95% CI), p NIRS desat: OR (95% CI), p Overlap: OR (95% CI), p Age (per year) 1.05 (0.87–1.26), 0.611 0.96 (0.73–1.27), 0.786 1.43 (0.99–2.06), 0.055 Weight (per kg) 1.01 (0.97–1.06), 0.668 1.00 (0.93–1.06), 0.887 1.10 (1.00–1.20), 0.044 Left SVC (yes vs no) 1.41 (0.71–2.81), 0.332 0.45 (0.11–1.91), 0.280 5.17 (0.93–28.81), 0.061 Ventricular morphology (RV-dominant vs LV-dominant) 1.71 (1.07–2.72), 0.025 0.73 (0.40–1.33), 0.303 0.35 (0.06–1.94), 0.230 Baseline SVC pressure at T0 (per mmHg) 1.01 (0.94–1.08), 0.793 1.02 (0.93–1.13), 0.660 1.04 (0.80–1.35), 0.768 Baseline rSO₂ at T0 (per %) 0.99 (0.94–1.05), 0.723 1.01 (0.93–1.09), 0.837 1.00 (0.82–1.22), 0.993 Preop mean PAP (per mmHg)* 0.97 (0.86–1.10), 0.628 0.96 (0.81–1.14), 0.646 0.88 (0.51–1.50), 0.631 Preop PVR (per WU·m²)* 0.77 (0.41–1.43), 0.407 1.03 (0.44–2.40), 0.950 3.45 (0.25–46.90), 0.352 Center (Center 2 vs Center 1) 1.24 (0.80–1.92), 0.329 1.29 (0.70–2.37), 0.407 1.02 (0.20–5.08), 0.983 Values are odds ratios (OR) from univariable logistic regression. “NIRS desat” indicates cerebral rSO₂ desaturation ≥ 20% from baseline at any time during clamping. “Overlap” indicates meeting both criteria (TSG < 30 and NIRS desat). Catheterization-derived PAP/PVR were available in a subset (n = 350). Overlap events were uncommon (n = 9), therefore confidence intervals are wide and estimates should be interpreted as exploratory. Table 2 Multivariable predictors of protocol-triggering physiology during SVC clamping Predictor Model 1 (TSG < 30): aOR (95% CI), p Model 2 (NIRS desat): aOR (95% CI), p Age (per year) 1.04 (0.87–1.26), 0.650 0.97 (0.73–1.28), 0.813 Left SVC (yes vs no) 1.42 (0.71–2.84), 0.320 0.46 (0.11–1.95), 0.293 Baseline T0 SVC (per mmHg) / Baseline T0 rSO₂ (per %) 1.01 (0.94–1.08), 0.785 1.01 (0.93–1.09), 0.858 Center (Center 2 vs Center 1) 1.25 (0.81–1.94), 0.310 1.28 (0.70–2.35), 0.429 Ventricular morphology (RV-dominant vs LV-dominant) 1.91 (1.20–3.04), 0.006 — aOR indicates adjusted odds ratio. Model 1 outcome: any TSG < 30 mmHg during clamping. Model 2 outcome: any rSO₂ desaturation ≥ 20% from baseline during clamping. Ventricular morphology was included in Model 1 due to its univariable association with TSG < 30. PAP/PVR were not included in primary multivariable models because these variables were available only in a subset (n = 350) and showed no univariable association; subset sensitivity analyses are reported in Supplementary Table S1. Overlap events (n = 9) were too few for a stable multivariable model. Comparison of patients with and without TSG < 30 mm Hg A total of 89 patients (12.8%) developed TSG < 30 mm Hg. ICU stay : Median ICU stay was 1.4 days (IQR 1.0–2.2) in the TSG < 30 mm Hg group versus 1.2 days (IQR 1.0–2.1) in the TSG ≥ 30 mm Hg group, with no significant difference (P = 0.604, Mann–Whitney U) ( Fig. 1 ). Inotrope requirement : Median number of inotropes was 2 (IQR 1–3) in the TSG < 30 mm Hg group and 1 (IQR 1–2) in the TSG ≥ 30 mm Hg group; this difference was not statistically significant (P = 0.793, Mann–Whitney U) ( Fig. 2 ). Pulmonary artery pressure : Mean postoperative pulmonary artery pressure was 11.3 (2.6) mm Hg in the TSG < 30 mm Hg group versus 11.0 (2.3) mm Hg in the TSG ≥ 30 mm Hg group (P = 0.533 ) ( Fig. 3 ). Intraoperative TSG and cerebral oximetry changes during SVC clamping Hemodynamic and cerebral oximetry changes during SVC clamping are summarized in Table 3 . Baseline values (T0) were similar between groups. One minute after clamping (T1), SVC pressure increased markedly, particularly in the TSG < 30 group (45.0 ± 4.3 vs 25.0 ± 4.0 mmHg), with a corresponding fall in TSG (24.2 ± 6.8 vs 50.0 ± 6.2 mmHg) and rSO₂ (62.2 ± 5.6% vs 68.1 ± 5.2%). The worst clamping physiology (T2) was characterized by higher peak SVC pressure and lower minimum rSO₂ in the TSG < 30 group (SVC_max 48.9 ± 4.9 vs 27.8 ± 4.0 mmHg; rSO₂_min 57.5 ± 5.8% vs 64.7 ± 4.9%). Following protocol-driven corrective maneuvers (T4), MAP was restored to comparable levels and was accompanied by a reduction in SVC pressure and improvement in TSG and rSO₂ (TSG < 30 group: TSG 24.2 ± 6.8 at T1 to 49.1 ± 6.4 mmHg at T4; Δ + 24.9 mmHg; rSO₂ 62.2 ± 5.6% to 68.1 ± 4.8%; Δ + 5.9%). After clamp release (T5), hemodynamic and rSO₂ values returned close to baseline in both groups. Table 3 Hemodynamic and cerebral oximetry changes across standardized time points during SVC clamping in off-pump bidirectional Glenn Time point Variable TSG ≥ 30 (n = 609) Mean (SD) TSG < 30 (n = 89) Mean (SD) Overall (n = 698) Mean (SD) T0 (Pre-clamp baseline; 1–3-min average) MAP (mmHg) 69.9 (4.9) 70.3 (5.2) 70.0 (4.9) SVC (mmHg) 12.3 (3.0) 12.4 (3.1) 12.3 (3.0) TSG (mmHg) 57.7 (5.8) 58.0 (5.9) 57.7 (5.8) rSO₂ (%) 72.2 (4.0) 72.4 (3.8) 72.2 (4.0) T1 (Clamp + 1 min) MAP (mmHg) 75.0 (4.8) 69.2 (4.5) 74.3 (5.2) SVC (mmHg) 25.0 (4.0) 45.0 (4.3) 27.6 (7.8) TSG (mmHg) 50.0 (6.2) 24.2 (6.8) 46.7 (10.7) rSO₂ (%) 68.1 (5.2) 62.2 (5.6) 67.3 (5.6) T2 (Worst during clamp) SVC_max (mmHg) 27.8 (4.0) 48.9 (4.9) 30.5 (8.2) rSO₂_min (%) 64.7 (4.9) 57.5 (5.8) 63.8 (5.6) T4 (2–3 min post-intervention) MAP (mmHg) 74.9 (4.9) 74.3 (5.2) 74.8 (4.9) SVC (mmHg) 19.9 (3.1) 25.3 (3.5) 20.6 (3.7) TSG (mmHg) 55.0 (5.8) 49.1 (6.4) 54.3 (6.2) rSO₂ (%) 69.8 (3.9) 68.1 (4.8) 69.6 (4.1) T5 (Clamp off + 1 min) MAP (mmHg) 71.9 (5.4) 72.0 (5.3) 72.0 (5.4) SVC (mmHg) 15.0 (3.1) 15.1 (2.9) 15.0 (3.1) TSG (mmHg) 56.9 (6.1) 56.9 (6.3) 56.9 (6.1) rSO₂ (%) 72.1 (4.2) 71.4 (3.8) 72.0 (4.2) Values are mean (SD). TSG = MAP − SVC pressure. TSG groups were defined by whether TSG ever fell below 30 mmHg during the clamp period (TSG < 30 vs TSG ≥ 30).T2 represents the worst clamping physiology and is reported as peak SVC pressure (SVC_max) and minimum cerebral rSO₂ (rSO₂_min) observed during clamping; MAP/TSG were not recorded as a standardized paired value at that exact “worst” moment in all cases and therefore are not shown for T2. In patients who met protocol criteria (TSG < 30 mmHg), corrective maneuvers were associated with a marked improvement in perfusion surrogates from T1 to T4: mean TSG increased from 24.2 ± 6.8 to 49.1 ± 6.4 mmHg (Δ + 24.9 mmHg), accompanied by a reduction in SVC pressure (45.0 ± 4.3 to 25.3 ± 3.5 mmHg; Δ − 19.7 mmHg) and an increase in cerebral rSO₂ (62.2 ± 5.6% to 68.1 ± 4.8%; Δ + 5.9%). After clamp release (T5), SVC pressure and rSO₂ returned close to baseline in both groups. Protocol-triggered venous decompression (blood withdrawal/reinfusion) By protocol, temporary autologous venous blood withdrawal with reinfusion was performed in all patients meeting the trigger criterion (TSG < 30 mm Hg; 89/89, 100%) and in none of those with TSG ≥ 30 mm Hg (0/609, 0%). As this intervention was conditional on TSG status by design, no hypothesis testing was performed and no P value is reported (Fig. 4 ). NIRS desaturation and its association with TSG Clinically significant cerebral desaturation (≥ 20% below baseline ) was observed in 54 patients (7.7%). Of these, 9 patients demonstrated concurrent TSG < 30 mm Hg, indicating overlap between invasive (TSG) and non-invasive (NIRS) indicators of cerebral vulnerability ( Fig. 5 ). Neurological outcomes Transient partial seizures occurred in 6 patients (0.86%) within the first 24 h postoperatively, all resolving without sequelae. Importantly, all seizure events occurred in patients with both TSG < 30 mm Hg and concurrent NIRS desaturation. No patient had persistent neurological deficit documented at ICU discharge. Box-and-whisker plot comparing ICU stay between patients with TSG ≥ 30 mm Hg and TSG < 30 mm Hg during off-pump bidirectional Glenn. The centre line denotes the median, the box denotes the interquartile range (IQR), and whiskers indicate the range (minimum–maximum). ICU stay did not differ significantly between groups ( Mann–Whitney U test, P = 0.6035 ). Box-and-whisker plot comparing the number of intraoperative inotropes administered in patients with TSG < 30 mm Hg versus TSG ≥ 30 mm Hg during off-pump BDG. The centre line denotes the median and the box denotes the IQR. No significant difference was observed between groups (Mann–Whitney U, P = 0.793). Points indicate mean postoperative pulmonary artery pressure (PAP) and error bars indicate SD. PAP was 11.3 (2.6) mm Hg in the TSG < 30 mm Hg group (n = 89) and 11.0 (2.3) mm Hg in the TSG ≥ 30 mm Hg group (n = 609), with no significant difference between groups (P = 0.533). All patients with TSG < 30 mmHg (n = 89, 12.8%) received protocol-defined venous withdrawal/reinfusion (89/89, 100%), whereas none of the patients with TSG ≥ 30 mmHg (n = 609, 87.2%) did (0/609, 0%). Because autologous venous withdrawal/reinfusion was a protocol-defined rescue step triggered by TSG < 30 mmHg, this intervention was performed only in patients meeting that criterion (89/89, 100%) and in none of those who did not (0/609, 0%). No hypothesis testing was performed for this protocol-defined contrast. Venn diagram showing the relationship between episodes of transcerebral gradient (TSG; mean arterial pressure minus superior vena cava pressure) < 30 mm Hg and clinically significant cerebral near-infrared spectroscopy (NIRS) desaturation (≥ 20% decrease from baseline) during off-pump bidirectional Glenn in the overall cohort (n = 698). TSG < 30 mm Hg occurred in 89 patients and NIRS desaturation in 54 patients, with 9 patients experiencing both events. Discussion The off-pump bidirectional Glenn (BDG) procedure has emerged as a valuable alternative to conventional cardiopulmonary bypass (CPB)-assisted techniques, particularly in paediatric patients with single-ventricle physiology. Avoidance of CPB mitigates systemic inflammatory activation, coagulopathy, transfusion-related complications, and potential cerebral reperfusion injury—effects that may be amplified in infants and young children [ 9 , 10 ]. Nevertheless, temporary superior vena cava (SVC) clamping during BDG introduces unique haemodynamic challenges by obstructing cerebral venous return, increasing SVC/central venous pressure (CVP), and potentially reducing effective cerebral perfusion [ 14 , 15 ]. Preservation of cerebral perfusion in this setting is a cornerstone of perioperative neuroprotection, and our study—reporting outcomes in 698 patients, the largest cohort to date—supports the feasibility of an integrated anaesthetic strategy targeting a transcerebral gradient (TSG) ≥ 30 mm Hg in combination with near-infrared spectroscopy (NIRS) monitoring to minimise cerebral risk while maintaining favourable perioperative recovery. TSG, defined as the difference between mean arterial pressure and SVC/CVP, has been used as a pragmatic surrogate for cerebral perfusion pressure during SVC occlusion, with values ≥ 30 mm Hg commonly regarded as a threshold that helps preserve autoregulation and limits venous congestion [ 8 , 16 ]. In our series, 12.8% of patients (n = 89) developed intraoperative TSG < 30 mm Hg. These episodes were managed using a standardised algorithm incorporating vasoactive titration (norepinephrine, with escalation to epinephrine and/or vasopressin when required), maintenance of azygos venous drainage, and temporary autologous central venous blood withdrawal with subsequent reinfusion after anastomosis. Importantly, there was no operative mortality, and only six patients (0.85%) experienced transient partial seizures within the first 24 h postoperatively, all resolving without sequelae. Notably, all neurological events occurred in the subset with concomitant TSG < 30 mm Hg and NIRS desaturation, underscoring the clinical relevance of integrating invasive haemodynamic targets with real-time cerebral oxygenation monitoring. These findings extend earlier smaller series by Hoffman et al. [ 14 ] and Salazar et al. [ 15 ], which highlighted the vulnerability to cerebral hypoperfusion during off-pump BDG and the potential value of targeted protective strategies. Cerebral NIRS monitoring has become an important component of paediatric cardiac anaesthesia, providing continuous, non-invasive assessment of cerebral oxygenation and enabling early detection of adverse trends before overt clinical deterioration [ 17 ]. In our cohort, clinically important desaturation (≥ 20% fall from baseline) occurred in 54 patients (7.7%), with 9 cases demonstrating concomitant TSG < 30 mm Hg. This overlap supports the complementary role of NIRS alongside invasive perfusion surrogates and is consistent with prior work demonstrating associations between intraoperative cerebral oximetry and neurological outcomes [ 18 , 19 ]. More importantly, protocolised corrective actions—including haemodynamic optimisation, ventilatory adjustment, haematocrit correction, and preservation of azygos venous drainage—were effective in restoring cerebral oxygenation and were not associated with permanent neurological injury. Standardising these responses may reduce practice variability and strengthen team-level adherence to neuroprotective goals during SVC clamping. Broader perioperative outcomes further support the clinical stability of this approach. Despite intraoperative differences in perfusion surrogates, intensive care unit (ICU) stay (1.4 vs 1.2 days), inotrope requirements, and postoperative pulmonary artery pressures did not differ significantly between patients with TSG 0.05). Universal extubation in the operating room (100%) was achieved, consistent with the systemic benefits of avoiding CPB and its inflammatory burden. These findings align with prior reports of reduced morbidity and accelerated recovery in selected off-pump BDG cohorts [ 4 , 9 , 10 ]. In addition, routine preservation of azygos venous drainage during the anastomosis may have contributed to favourable neurological outcomes, in keeping with data suggesting improved haemodynamic tolerance when cerebral venous egress is maintained [ 20 ]. The early neurological event rate of 0.85% observed in this study is lower than the 2–5% range reported in previous off-pump BDG cohorts [ 5 , 21 ]. While this difference may reflect advances in perioperative monitoring and care pathways over time, it also supports the potential value of combining a prespecified TSG target with NIRS-triggered, stepwise interventions. The large sample size strengthens the reproducibility of these observations compared with earlier reports limited by smaller cohorts and heterogeneous thresholds or rescue strategies [ 3 , 13 , 15 ]. Collectively, our findings add to growing evidence that proactive multimodal monitoring and algorithm-based responses can reduce neurological morbidity in this high-risk population. Several limitations should be acknowledged. The retrospective observational design introduces the potential for selection bias, and the absence of randomised comparison precludes causal inference. Furthermore, while early neurological events were systematically captured within 24 h, structured long-term neurodevelopmental follow-up was not performed [ 21 , 22 ]. Several limitations should be acknowledged. The retrospective observational design introduces the potential for selection bias, and the absence of a randomized comparator precludes causal inference. Neurological follow-up was limited to early clinical surveillance and clinically triggered testing within the first 24 h; routine EEG or standardized neuroimaging was not performed in all patients. Therefore, subclinical events and longer-term neurodevelopmental outcomes may have been missed, and prospective studies with predefined neurological assessments are warranted. However, 147 patients subsequently returned for Fontan completion at our institution with a median interval of 5 years (range 2–9 years), and clinical neurological assessments during pre-Fontan evaluation did not identify overt neurological deficits. This observation is reassuring but does not replace standardized neurocognitive testing, and subtle deficits may manifest later. Prospective multicentre studies incorporating predefined neurodevelopmental endpoints are warranted to validate these findings and to refine optimal age-specific thresholds for both TSG and NIRS during off-pump cavopulmonary connection. However, 147 patients subsequently returned for Fontan completion at our institution with a median interval of 5 years (range 2–9 years), and clinical neurological assessments during pre-Fontan evaluation did not identify overt neurological deficits. This observation is reassuring but does not replace standardised neurocognitive testing, and subtle deficits may manifest later, as highlighted in prior literature [ 21 – 23 ]. Prospective multicentre studies incorporating predefined neurodevelopmental endpoints are warranted to validate these findings and to refine optimal age-specific thresholds for both TSG and NIRS in off-pump cavopulmonary connection. In conclusion, our 698-patient two-centre experience demonstrates that a standardised algorithm targeting TSG ≥ 30 mm Hg, integrated with continuous cerebral NIRS monitoring and stepwise corrective actions, is feasible during off-pump BDG and is associated with low rates of clinically important cerebral desaturation and early neurological events. These data support consideration of integrated TSG–NIRS protocols as a reproducible framework for cerebral protection during off-pump BDG, while underscoring the need for prospective validation with long-term neurodevelopmental follow-up. Conclusion In this large retrospective cohort of 698 pediatric patients undergoing off-pump bidirectional Glenn (BDG) anastomosis, a goal-directed anesthetic strategy targeting a transcerebral gradient (TSG) ≥ 30 mm Hg and integrated with near-infrared spectroscopy (NIRS) monitoring was feasible and was associated with favorable early clinical outcomes. This multimodal approach—including titrated vasoactive support, maintenance of azygos venous drainage, hematocrit optimization, and protocolized autologous central venous blood withdrawal with reinfusion—was associated with a very low rate of transient neurological events (0.85%), universal extubation in the operating room, and stable postoperative hemodynamics without operative mortality. Prospective studies incorporating standardized neurodevelopmental follow-up are warranted to confirm generalizability and to refine optimal thresholds for TSG and NIRS-guided interventions. These findings suggest that the incorporation of TSG and NIRS-guided interventions provides a reproducible framework for cerebral protection in high-risk paediatric patients undergoing cavopulmonary connection without cardiopulmonary bypass. While the retrospective design and absence of long-term neurodevelopmental follow-up remain important limitations, our data underscore the potential for this algorithm to serve as a standardized management protocol. Prospective multicenter trials with long-term neurocognitive assessment are warranted to validate these results and further define the role of integrated TSG–NIRS monitoring in optimizing outcomes after off-pump Glenn procedures. Declarations Ethics approval and consent to participate: This study was approved by the Clinical Research Ethics Committee of Medicana International Istanbul Hospital (Approval: December 2025; File No: 78). Given the retrospective nature of the study and the use of routinely collected clinical data, the requirement for individual informed consent was waived by the ethics committee. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Funding: No funding was received for this study. Author Contribution İbrahim Özgür Önsel ¹; Barış Kırat ¹;Mustafa Kemal Avşar ²; Onur Benli ²; Cenap Zeybek ³İ.Ö.Ö. and B.K. contributed to anesthesia planning, intraoperative management, and data collection. M.K.A. and OB designed the study, performed surgical procedures, supervised data analysis, and drafted the initial manuscript. C.Z. contributed to patient follow-up, clinical data acquisition, and interpretation of echocardiographic and hemodynamic findings. OB. assisted with perioperative management, surgical logistics, and data validation. All authors critically revised the manuscript, approved the final version, and agree to be accountable for all aspects of the work. Acknowledgements: The authors would like to thank the operating room nurses, anesthesia technicians, and intensive care unit staff for their valuable contributions to the surgical care of the patients. References Glenn WW. Circulatory bypass of the right side of the heart. IV. Shunt between superior vena cava and distal right pulmonary artery; report of clinical application. N Engl J Med. 1958;259(3):117–20. 10.1056/NEJM195807172590304 . Mahle WT, Tavani F, Zimmerman RA, et al. An MRI study of neurological injury before and after congenital heart surgery. Circulation. 2002;106(12 Suppl 1):I109–14. 10.1161/01.cir.0000027563.40922.7f . Said SM, Burkhart HM, Dearani JA, et al. Off-pump bidirectional Glenn: a safe and effective technique. Ann Thorac Surg. 2012;94(2):592–8. 10.1016/j.athoracsur.2012.04.041 . Giamberti A, Chessa M, Abella R, et al. Off-pump bidirectional cavopulmonary shunt: indications and results. Eur J Cardiothorac Surg. 2006;30(4):545–9. 10.1016/j.ejcts.2006.07.013 . Jonas RA. Neurological protection during cardiopulmonary bypass/deep hypothermic circulatory arrest. Pediatr Cardiol. 2009;30(5):635–43. 10.1007/s00246-009-9409-6 . Andropoulos DB, Hunter JV, Nelson DP, et al. Brain immaturity is associated with brain injury before and after neonatal cardiac surgery with high-flow bypass and cerebral oxygenation monitoring. J Thorac Cardiovasc Surg. 2013;145(3):870–8. 10.1016/j.jtcvs.2012.10.043 . Kern JH, Hinton VJ, Agostino CD, et al. Cerebral blood flow and metabolism in infants undergoing the bidirectional Glenn procedure. J Thorac Cardiovasc Surg. 1999;117(1):156–63. 10.1016/S0022-5223(99)70407-9 . Brady KM, Lee JK, Kibler KK, et al. Continuous measurement of autoregulation by spontaneous fluctuations in cerebral perfusion pressure: comparison of transcranial Doppler and near-infrared spectroscopy. Stroke. 2008;39(9):2531–7. 10.1161/STROKEAHA.108.514877 . Visconti KJ, Rimmer D, Gauvreau K, et al. Regional low-flow perfusion versus circulatory arrest in neonates: one-year neurodevelopmental outcome. Ann Thorac Surg. 2006;82(6):2207–13. 10.1016/j.athoracsur.2006.06.087 . Hosein RB, Clarke AJ, McGuirk SP, et al. Factors influencing early outcome following the bidirectional Glenn procedure without cardiopulmonary bypass. Eur J Cardiothorac Surg. 2007;31(1):22–6. 10.1016/j.ejcts.2006.10.011 . Austin EH, Edmonds HL, Auden SM, et al. Benefit of neurophysiologic monitoring for pediatric cardiac surgery. J Thorac Cardiovasc Surg. 1997;114(5):707–15. 10.1016/S0022-5223(97)70074-4.​ . Licht DJ, Shera DM, Clancy RR, et al. Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg. 2009;137(3):529–36. 10.1016/j.jtcvs.2008.10.025 . Petrucci O, Khoury PR, Manning PB, et al. Outcomes of the bidirectional Glenn procedure in patients less than 3 months of age. J Thorac Cardiovasc Surg. 2010;139(3):562–8. 10.1016/j.jtcvs.2009.08.025 . Hoffman GM, Stuth EA, Jaquiss RD, et al. Cerebral autoregulation and oxygenation during bidirectional Glenn shunt without cardiopulmonary bypass. Ann Thorac Surg. 2006;82(5):1679–85. 10.1016/j.athoracsur.2006.05.089 . Salazar JD, Coleman RD, Griffith S, et al. Selective cerebral perfusion during bidirectional Glenn shunt without cardiopulmonary bypass. Ann Thorac Surg. 2010;89(3):951–6. 10.1016/j.athoracsur.2009.12.032 . Tweddell JS, Ghanayem NS, Mussatto KA, et al. Mixed venous oxygen saturation monitoring after stage 1 palliation for hypoplastic left heart syndrome. Ann Thorac Surg. 2007;84(4):1301–6. 10.1016/j.athoracsur.2007.05.019 . Kussman BD, Wypij D, Laussen PC, et al. Relationship of intraoperative cerebral oxygen saturation to neurodevelopmental outcome and brain magnetic resonance imaging at 1 year of age in infants undergoing biventricular repair. Circulation. 2010;122(3):245–54. 10.1161/CIRCULATIONAHA.109.902890 . Kurth CD, McCann JC, Wu J, et al. Cerebral oxygen saturation monitoring in pediatric cardiac surgery: relationship to perioperative neurologic outcomes. J Thorac Cardiovasc Surg. 2015;150(5):1237–43. 10.1016/j.jtcvs.2015.07.082 . Tortoriello TA, Stayer SA, Mott AR, et al. A noninvasive estimation of mixed venous oxygen saturation using near-infrared spectroscopy by cerebral oximetry in pediatric cardiac surgery patients. Paediatr Anaesth. 2008;18(6):495–503. 10.1111/j.1460-9592.2008.02487.x . Chacon MM, Gutsche JT, Dickinson TA, et al. Off-pump Glenn shunt: azygos vein preservation improves outcomes. Ann Thorac Surg. 2019;108(5):1432–8. 10.1016/j.athoracsur.2019.04.047 . McQuillen PS, Barkovich AJ, Hamrick SE, et al. Temporal and anatomic risk profile of brain injury with neonatal repair of congenital heart defects. Stroke. 2007;38(2 Suppl):736–41. 10.1161/01.STR.0000247941.41234.90 . Marino BS, Lipkin PH, Newburger JW et al. Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association. Circulation. 2012;126(9):1143–1172. 10.1161/CIR.0b013e318265ee8a Alsoufi B, McCracken C, Kanter K, et al. Outcomes of multistage palliation of infants with single ventricle and atrioventricular septal defect. World J Pediatr Congenit Heart Surg. 2020;11(1):39–48. 10.1177/2150135119885890 . Additional Declarations No competing interests reported. Supplementary Files SupplementaryTableS1.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 10 Mar, 2026 Reviews received at journal 08 Mar, 2026 Reviewers agreed at journal 26 Feb, 2026 Reviews received at journal 23 Feb, 2026 Reviewers agreed at journal 23 Feb, 2026 Reviewers invited by journal 23 Feb, 2026 Editor invited by journal 13 Feb, 2026 Editor assigned by journal 23 Jan, 2026 Submission checks completed at journal 23 Jan, 2026 First submitted to journal 17 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8624939","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":597445130,"identity":"60d1f034-9c94-4ac5-ad8a-cf19d62f95bf","order_by":0,"name":"ibrahim özgür önsel","email":"","orcid":"","institution":"Medicana International Istanbul Hospital","correspondingAuthor":false,"prefix":"","firstName":"ibrahim","middleName":"özgür","lastName":"önsel","suffix":""},{"id":597445131,"identity":"1ef3c31b-0284-4806-9f28-3a8298ac37f9","order_by":1,"name":"Barış Kırat","email":"","orcid":"","institution":"Medicana International Istanbul 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of stay by transcerebral gradient (TSG) status.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/d5efb823d5a2e1464b9e06dc.png"},{"id":104400908,"identity":"0d557bae-69f4-47dd-b94d-e1143705e428","added_by":"auto","created_at":"2026-03-11 12:11:24","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17733,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eInotrope requirement by transcerebral gradient (TSG) status.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/20a9b3a61b4833c34640b491.png"},{"id":103837707,"identity":"27b7d62b-a117-4400-95d9-2de2d4c7b2d8","added_by":"auto","created_at":"2026-03-03 14:17:59","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":23842,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePostoperative pulmonary artery pressure by TSG group.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/432531071a56a28d757ee4ca.png"},{"id":104400921,"identity":"6c257837-6599-4990-9b6e-9258737021f0","added_by":"auto","created_at":"2026-03-11 12:11:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26038,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCentral venous blood withdrawal/reinfusion by transcerebral gradient (TSG) group.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/69ac9a92474cf61ad1ed305e.png"},{"id":103837708,"identity":"3748b7b5-ab21-47a9-8f58-ade4a54a20c4","added_by":"auto","created_at":"2026-03-03 14:17:59","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":63142,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eOverlap between intraoperative TSG \u0026lt;30 mm Hg and cerebral NIRS desaturation.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/6939d940b2281d9dde7a8e58.png"},{"id":104408223,"identity":"90b9354d-b61c-470b-88f9-29dc51cc6632","added_by":"auto","created_at":"2026-03-11 12:42:01","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1380345,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/f32ad1a2-bde2-4516-a4a4-4a3d7531dfc5.pdf"},{"id":103837706,"identity":"6d3fc6e0-bb9e-4de7-9436-7e502c7ceb66","added_by":"auto","created_at":"2026-03-03 14:17:59","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14914,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTableS1.docx","url":"https://assets-eu.researchsquare.com/files/rs-8624939/v1/01da595f92d2b3999f9c61a2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Cerebral Protection via Transcerebral Gradient-Guided Strategy in Pediatric Bidirectional Glenn","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBidirectional Glenn (BDG) anastomosis is a key second-stage palliation for children with single-ventricle physiology, directing superior vena cava (SVC) flow to the pulmonary arteries (1). Although BDG has traditionally been performed with cardiopulmonary bypass (CPB), many centres now undertake selected cases off-pump to avoid CPB-associated inflammatory activation, coagulopathy and transfusion-related complications, and potential cerebral reperfusion injury\u0026mdash;effects that may be amplified in infants and young children (2\u0026ndash;4).\u003c/p\u003e \u003cp\u003eA specific challenge of the off-pump approach is temporary SVC clamping, which increases SVC pressure, impedes cerebral venous drainage, and may reduce effective cerebral perfusion pressure.5,6 Neurological complications have been reported in approximately 2\u0026ndash;5% of off-pump BDG cohorts, underscoring the need for reliable intraoperative surrogates of cerebral perfusion and standardised rescue strategies (3\u0026ndash;6).\u003c/p\u003e \u003cp\u003eThe arterial-to-venous pressure gradient during SVC occlusion\u0026mdash;commonly expressed as mean arterial pressure minus SVC/central venous pressure\u0026mdash;has been used as a pragmatic haemodynamic surrogate for cerebral perfusion (here termed transcerebral gradient, TSG) (7,8). In parallel, near-infrared spectroscopy (NIRS) provides continuous, non-invasive monitoring of cerebral oxygenation and can detect deteriorating trends before overt clinical signs emerge.9,10 However, published reports rarely describe integrated protocols that combine a prespecified TSG target with NIRS-triggered, stepwise interventions; existing series are typically small and use heterogeneous thresholds and responses (11\u0026ndash;13).\u003c/p\u003e \u003cp\u003eWe hypothesised that a goal-directed algorithm targeting TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg, coupled with NIRS-guided corrective actions during SVC clamping, would reduce clinically important cerebral desaturation and early neurological events during off-pump BDG. We therefore evaluated the feasibility and early outcomes of a standardised TSG\u0026ndash;NIRS strategy in 698 consecutive paediatric patients undergoing off-pump BDG at two tertiary centres.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and setting\u003c/h2\u003e \u003cp\u003eThis retrospective, observational two-centre cohort study included paediatric patients undergoing off-pump bidirectional Glenn (BDG) anastomosis between 2016 and 2025 at two tertiary cardiac surgery centres. Institutional approval was obtained at both centres, and the study was conducted in accordance with the Declaration of Helsinki.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eChildren aged 4 months to 15\u0026nbsp;year with single-ventricle physiology scheduled for second-stage palliation after prior systemic-to-pulmonary shunt were eligible. Patients with documented pre-existing neurological sequelae, or a history of previous Glenn or Fontan procedures, were excluded.\u003c/p\u003e\n\u003ch3\u003ePatient selection and potential selection bias\u003c/h3\u003e\n\u003cp\u003eDuring the study period, 1,621 BDG procedures were performed; 698 (43.1%) were completed off-pump and 923 (56.9%) were performed with CPB. The present analysis includes the off-pump cohort. Of these, 698 (43.1%) were completed without cardiopulmonary bypass (off-pump BDG) and constitute the study cohort, while 923 (56.9%) were performed with CPB.\u003c/p\u003e \u003cp\u003eOff-pump BDG was the default strategy when predefined anatomical and hemodynamic conditions allowed safe superior vena cava (SVC) clamping and cavopulmonary anastomosis without additional major surgical steps. BDG was performed with CPB primarily when concomitant surgical procedures were required or when anatomical complexity was expected to prolong clamp time and reduce the safety margin of an off-pump strategy. In our practice, the most common indications for CPB use were pulmonary artery reconstruction (including patch augmentation/plasty and complex pulmonary artery work) and additional intracardiac/great-vessel procedures such as atrial septectomy, ventricular septal defect (VSD) enlargement, and aortic arch reconstruction. Indications for CPB use were extracted from operative and anesthesia records and are summarized in Table S1.\u003c/p\u003e\n\u003ch3\u003eAnaesthesia and haemodynamic monitoring\u003c/h3\u003e\n\u003cp\u003eA standardised general anaesthetic protocol was used. Induction included ketamine 2 mg kg⁻\u0026sup1;, fentanyl 2\u0026ndash;3 \u0026micro;g kg⁻\u0026sup1;, and midazolam; maintenance consisted of sevoflurane 0.5\u0026ndash;1% with propofol infusion 50\u0026ndash;100 \u0026micro;g kg⁻\u0026sup1; min⁻\u0026sup1; and remifentanil, titrated to clinical effect. Continuous invasive arterial pressure monitoring was obtained via a radial arterial catheter. Central venous (SVC) pressure was measured via an internal jugular or subclavian catheter with the catheter tip positioned in the superior vena cava.\u003c/p\u003e \u003cp\u003eSuperior vena cava (SVC) pressure was measured via a central venous catheter inserted through the internal jugular or subclavian vein. For continuous and physiologically relevant measurement during SVC clamping, the catheter tip was deliberately kept cranial to (i.e., \u0026ldquo;above\u0026rdquo;) the surgical clamp so that the recorded pressure reflected the venous segment draining the head and neck during occlusion. When the planned clamp position would otherwise overlap the catheter tip, the catheter was withdrawn under sterile conditions to maintain the tip cranial to the clamp site. Catheter position was verified by waveform characteristics and intraoperative team confirmation. Transcerebral gradient (TSG) was calculated continuously as mean arterial pressure minus SVC pressure (MAP\u0026thinsp;\u0026minus;\u0026thinsp;SVC). This setup allowed uninterrupted tracking of SVC pressure and TSG evolution before, during, and after clamping across the predefined time points.\u003c/p\u003e\n\u003ch3\u003eTranscerebral gradient (TSG) and treatment algorithm\u003c/h3\u003e\n\u003cp\u003eTSG was defined as mean arterial pressure minus SVC pressure, and the intraoperative target was TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg during SVC clamping and anastomosis. When TSG fell below 30 mm Hg, norepinephrine 0.05\u0026ndash;0.2 \u0026micro;g kg⁻\u0026sup1; min⁻\u0026sup1; was initiated and titrated; epinephrine and/or vasopressin were added when required. If targets could not be restored promptly, temporary autologous venous blood withdrawal (3\u0026ndash;5 ml kg⁻\u0026sup1;) was performed via the central venous line into sterile collection bags to reduce venous pressure, with reinfusion after completion of the anastomosis.\u003c/p\u003e \u003cp\u003eTSG and cerebral rSO₂ were documented at standardized time points on the anesthesia record: T0 (pre-clamp baseline; 1\u0026ndash;3-min average immediately before SVC clamping), T1 (1 min after clamping), T2 (worst values during clamping, defined as peak SVC pressure and minimum rSO₂ observed during the clamp period), T4 (2\u0026ndash;3 min after completion of the corrective maneuver), and T5 (1 min after clamp release). At each time point, MAP, SVC pressure, calculated TSG (MAP\u0026thinsp;\u0026minus;\u0026thinsp;SVC), and rSO₂ were recorded when applicable.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eCerebral NIRS monitoring and stepwise rescue protocol\u003c/h2\u003e \u003cp\u003eBilateral frontal cerebral regional oxygen saturation (rSO₂) was monitored continuously using near-infrared spectroscopy (NIRS). Baseline rSO₂ was defined as the average value recorded during a stable pre-clamp period. Clinically important desaturation was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;20% decrease from baseline. When rSO₂ desaturation and/or TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg occurred, a prespecified stepwise rescue protocol was applied: (i) vasoactive titration to increase arterial pressure, (ii) ventilatory optimisation targeting PaCO₂ 4.7\u0026ndash;5.3 kPa (35\u0026ndash;40 mm Hg), (iii) maintenance of azygos venous drainage during anastomosis, (iv) haematocrit optimisation (RBC transfusion if haematocrit\u0026thinsp;\u0026lt;\u0026thinsp;30%), and (v) venous decompression and/or reinfusion according to protocol response. The TSG\u0026ndash;NIRS algorithm and intervention sequence were implemented as a shared institutional protocol at both centers. Thresholds (TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg; rSO₂ desaturation\u0026thinsp;\u0026ge;\u0026thinsp;20% from baseline) and the stepwise rescue actions were predefined and identical across sites. Although vasoactive selection and titration were individualized to patient physiology, all interventions were delivered within the same ordered framework (hemodynamic optimization, ventilatory adjustment, hematocrit optimization, maintenance of azygos drainage, and venous decompression when indicated). Center was included as a covariate in regression analyses to account for potential inter-center practice variability. The time point T4 was specifically defined to capture the physiologic response 2\u0026ndash;3 minutes after the principal corrective maneuver was implemented.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eSurgical technique\u003c/h3\u003e\n\u003cp\u003eAll off-pump BDG procedures in the study cohort were performed through median sternotomy without cardiopulmonary bypass. During SVC clamping, the azygos vein was kept patent to facilitate cerebral venous drainage and was ligated after completion of the anastomosis.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe prespecified outcomes were: (i) clinically important cerebral NIRS desaturation during SVC clamping, (ii) occurrence of intraoperative TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg, and (iii) early neurological events within the first 24 h after surgery. Seizure events were defined as clinically observed focal seizures documented in the medical record within 24 h postoperatively (with neurology review and additional testing performed according to local practice). TSG\u0026thinsp;\u0026lt;\u0026thinsp;30, NIRS desat, overlap (n\u0026thinsp;=\u0026thinsp;9).All patients underwent a standardized immediate postoperative neurological surveillance pathway in the ICU. A focused neurological examination was documented on ICU arrival and at regular intervals during the first 24 h (level of consciousness/behavior, pupillary response, motor symmetry, and presence of abnormal movements). Clinically suspected seizures triggered bedside neurology review and additional testing (e.g., EEG and/or neuroimaging) according to local availability and clinical judgment. Neurological events for this study were defined as clinically observed focal or generalized seizures within 24 h, recorded in the medical chart and adjudicated by ICU and anesthesia teams.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eContinuous variables were assessed for distributional assumptions and summarised as mean (SD) or median (IQR), as appropriate; categorical variables were reported as n (%). Group comparisons (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 vs\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg) used Student\u0026rsquo;s t-test or Mann\u0026ndash;Whitney U test for continuous variables and χ\u0026sup2; test or Fisher\u0026rsquo;s exact test for categorical variables. A two-sided P value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. Reporting followed the BJA style for units\u003c/p\u003e \u003cp\u003eTo explore factors associated with protocol-triggering physiology during SVC clamping, we performed logistic regression analyses for three predefined phenotypes: (i) TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg at any time during clamping, (ii) cerebral rSO₂ desaturation\u0026thinsp;\u0026ge;\u0026thinsp;20% from baseline at any time during clamping, and (iii) the overlap phenotype meeting both criteria. Univariable logistic regression was used to screen candidate predictors (age, weight, ventricular morphology [RV-dominant vs LV-dominant], presence of left SVC, baseline T0 SVC pressure, baseline T0 rSO₂, and center). Multivariable logistic regression models were then constructed for TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 and for rSO₂ desaturation, including prespecified covariates (age, center) and clinically relevant variables; ventricular morphology was included in the adjusted model for TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 given its univariable association. Catheterization-derived mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) were available in a subset of patients (n\u0026thinsp;=\u0026thinsp;350) and were evaluated in sensitivity analyses restricted to this subset. Results are reported as odds ratios (OR) or adjusted odds ratios (aOR) with 95% confidence intervals.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e1,621 BDG procedures performed during the study period, 698 (43.1%) were completed off-pump and 923 (56.9%) were performed with CPB; the present analysis includes the off-pump cohort. Among 698 pediatric patients included, ages ranged from 4 months to 15 years (median: 1.8 years). All patients in the study cohort underwent BDG anastomosis without CPB. Continuous intraoperative monitoring with NIRS and invasive TSG measurement was achieved in all cases.\u003c/p\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eFactors associated with protocol-triggering physiology\u003c/h2\u003e \u003cp\u003eUnivariable analyses of candidate predictors are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. RV-dominant ventricular morphology was associated with TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg during clamping (OR 1.71, 95% CI 1.07\u0026ndash;2.72; p\u0026thinsp;=\u0026thinsp;0.025). The overlap phenotype (both TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 and rSO₂ desaturation) occurred in 9 patients (1.3%) and showed exploratory associations with higher weight (OR 1.10 per kg, 95% CI 1.00\u0026ndash;1.20; p\u0026thinsp;=\u0026thinsp;0.044) and the presence of a left SVC (OR 5.17, 95% CI 0.93\u0026ndash;28.81; p\u0026thinsp;=\u0026thinsp;0.061), with wide confidence intervals reflecting low event counts. In multivariable models adjusting for prespecified covariates (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), no variable was independently associated with rSO₂ desaturation, whereas ventricular morphology remained independently associated with TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 (aOR 1.91, 95% CI 1.20\u0026ndash;3.04; p\u0026thinsp;=\u0026thinsp;0.006). Catheterization-derived PAP/PVR were evaluated in the subset with available data (n\u0026thinsp;=\u0026thinsp;350) as a sensitivity analysis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariable predictors of protocol-triggering physiology during SVC clamping\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePredictor (unit)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTSG\u0026thinsp;\u0026lt;\u0026thinsp;30: OR (95% CI), p\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNIRS desat: OR (95% CI), p\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eOverlap: OR (95% CI), p\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (per year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.05 (0.87\u0026ndash;1.26), 0.611\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.96 (0.73\u0026ndash;1.27), 0.786\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.43 (0.99\u0026ndash;2.06), 0.055\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (per kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.97\u0026ndash;1.06), 0.668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.00 (0.93\u0026ndash;1.06), 0.887\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.10 (1.00\u0026ndash;1.20), 0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLeft SVC (yes vs no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.41 (0.71\u0026ndash;2.81), 0.332\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.45 (0.11\u0026ndash;1.91), 0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5.17 (0.93\u0026ndash;28.81), 0.061\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVentricular morphology (RV-dominant vs LV-dominant)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.71 (1.07\u0026ndash;2.72), 0.025\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.73 (0.40\u0026ndash;1.33), 0.303\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.35 (0.06\u0026ndash;1.94), 0.230\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline SVC pressure at T0 (per mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.01 (0.94\u0026ndash;1.08), 0.793\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.02 (0.93\u0026ndash;1.13), 0.660\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.04 (0.80\u0026ndash;1.35), 0.768\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBaseline rSO₂ at T0 (per %)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.99 (0.94\u0026ndash;1.05), 0.723\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.01 (0.93\u0026ndash;1.09), 0.837\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.00 (0.82\u0026ndash;1.22), 0.993\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreop mean PAP (per mmHg)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.97 (0.86\u0026ndash;1.10), 0.628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.96 (0.81\u0026ndash;1.14), 0.646\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.88 (0.51\u0026ndash;1.50), 0.631\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreop PVR (per WU\u0026middot;m\u0026sup2;)*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.77 (0.41\u0026ndash;1.43), 0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.03 (0.44\u0026ndash;2.40), 0.950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.45 (0.25\u0026ndash;46.90), 0.352\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCenter (Center 2 vs Center 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.24 (0.80\u0026ndash;1.92), 0.329\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.29 (0.70\u0026ndash;2.37), 0.407\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.02 (0.20\u0026ndash;5.08), 0.983\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eValues are odds ratios (OR) from univariable logistic regression. \u0026ldquo;NIRS desat\u0026rdquo; indicates cerebral rSO₂ desaturation\u0026thinsp;\u0026ge;\u0026thinsp;20% from baseline at any time during clamping. \u0026ldquo;Overlap\u0026rdquo; indicates meeting both criteria (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 and NIRS desat). Catheterization-derived PAP/PVR were available in a subset (n\u0026thinsp;=\u0026thinsp;350). Overlap events were uncommon (n\u0026thinsp;=\u0026thinsp;9), therefore confidence intervals are wide and estimates should be interpreted as exploratory.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariable predictors of protocol-triggering physiology during SVC clamping\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePredictor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eModel 1 (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30): aOR (95% CI), p\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eModel 2 (NIRS desat): aOR (95% CI), p\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (per year)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.04 (0.87\u0026ndash;1.26), 0.650\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.97 (0.73\u0026ndash;1.28), 0.813\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft SVC (yes vs no)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.42 (0.71\u0026ndash;2.84), 0.320\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.46 (0.11\u0026ndash;1.95), 0.293\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBaseline T0 SVC (per mmHg) / Baseline T0 rSO₂ (per %)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.01 (0.94\u0026ndash;1.08), 0.785\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.01 (0.93\u0026ndash;1.09), 0.858\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCenter (Center 2 vs Center 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.25 (0.81\u0026ndash;1.94), 0.310\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.28 (0.70\u0026ndash;2.35), 0.429\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVentricular morphology (RV-dominant vs LV-dominant)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.91 (1.20\u0026ndash;3.04), 0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026mdash;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eaOR indicates adjusted odds ratio. Model 1 outcome: any TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg during clamping. Model 2 outcome: any rSO₂ desaturation\u0026thinsp;\u0026ge;\u0026thinsp;20% from baseline during clamping. Ventricular morphology was included in Model 1 due to its univariable association with TSG\u0026thinsp;\u0026lt;\u0026thinsp;30. PAP/PVR were not included in primary multivariable models because these variables were available only in a subset (n\u0026thinsp;=\u0026thinsp;350) and showed no univariable association; subset sensitivity analyses are reported in Supplementary Table S1. Overlap events (n\u0026thinsp;=\u0026thinsp;9) were too few for a stable multivariable model.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eComparison of patients with and without TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg\u003c/h2\u003e \u003cp\u003eA total of 89 patients (12.8%) developed TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eICU stay\u003c/b\u003e: Median ICU stay was 1.4 days (IQR 1.0\u0026ndash;2.2) in the TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg group versus 1.2 days (IQR 1.0\u0026ndash;2.1) in the TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg group, with no significant difference (P\u0026thinsp;=\u0026thinsp;0.604, Mann\u0026ndash;Whitney U) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eInotrope requirement\u003c/b\u003e: Median number of inotropes was 2 (IQR 1\u0026ndash;3) in the TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg group and 1 (IQR 1\u0026ndash;2) in the TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg group; this difference was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.793, Mann\u0026ndash;Whitney U) \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003ePulmonary artery pressure\u003c/b\u003e: Mean postoperative pulmonary artery pressure was 11.3 (2.6) mm Hg in the TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg group versus 11.0 (2.3) mm Hg in the TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg group (P\u0026thinsp;=\u0026thinsp;0.533\u003cb\u003e) (\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eIntraoperative TSG and cerebral oximetry changes during SVC clamping\u003c/h2\u003e \u003cp\u003eHemodynamic and cerebral oximetry changes during SVC clamping are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Baseline values (T0) were similar between groups. One minute after clamping (T1), SVC pressure increased markedly, particularly in the TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 group (45.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 vs 25.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 mmHg), with a corresponding fall in TSG (24.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 vs 50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2 mmHg) and rSO₂ (62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6% vs 68.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.2%). The worst clamping physiology (T2) was characterized by higher peak SVC pressure and lower minimum rSO₂ in the TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 group (SVC_max 48.9\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9 vs 27.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.0 mmHg; rSO₂_min 57.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8% vs 64.7\u0026thinsp;\u0026plusmn;\u0026thinsp;4.9%). Following protocol-driven corrective maneuvers (T4), MAP was restored to comparable levels and was accompanied by a reduction in SVC pressure and improvement in TSG and rSO₂ (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 group: TSG 24.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 at T1 to 49.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 mmHg at T4; Δ\u0026thinsp;+\u0026thinsp;24.9 mmHg; rSO₂ 62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6% to 68.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8%; Δ\u0026thinsp;+\u0026thinsp;5.9%). After clamp release (T5), hemodynamic and rSO₂ values returned close to baseline in both groups.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eHemodynamic and cerebral oximetry changes across standardized time points during SVC clamping in off-pump bidirectional Glenn\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime point\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTSG\u0026thinsp;\u0026ge;\u0026thinsp;30 (n\u0026thinsp;=\u0026thinsp;609) Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTSG\u0026thinsp;\u0026lt;\u0026thinsp;30 (n\u0026thinsp;=\u0026thinsp;89) Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;698) Mean (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT0\u003c/b\u003e\u0026nbsp;(Pre-clamp baseline; 1\u0026ndash;3-min average)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69.9 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e70.3 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e70.0 (4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVC (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12.3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12.4 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e12.3 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTSG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e57.7 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e58.0 (5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e57.7 (5.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003erSO₂ (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72.2 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72.4 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e72.2 (4.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT1\u003c/b\u003e\u0026nbsp;(Clamp\u0026thinsp;+\u0026thinsp;1 min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75.0 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e69.2 (4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e74.3 (5.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVC (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25.0 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e45.0 (4.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e27.6 (7.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTSG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.0 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24.2 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e46.7 (10.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003erSO₂ (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e68.1 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e62.2 (5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e67.3 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT2\u003c/b\u003e\u0026nbsp;(Worst during clamp)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVC_max (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.8 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e48.9 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30.5 (8.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003erSO₂_min (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e64.7 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e57.5 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e63.8 (5.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT4\u003c/b\u003e\u0026nbsp;(2\u0026ndash;3 min post-intervention)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e74.9 (4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e74.3 (5.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e74.8 (4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVC (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.9 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25.3 (3.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e20.6 (3.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTSG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e55.0 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e49.1 (6.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e54.3 (6.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003erSO₂ (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e69.8 (3.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e68.1 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e69.6 (4.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eT5\u003c/b\u003e\u0026nbsp;(Clamp off +\u0026thinsp;1 min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e71.9 (5.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72.0 (5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e72.0 (5.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSVC (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.0 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15.1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15.0 (3.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTSG (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e56.9 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e56.9 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e56.9 (6.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003erSO₂ (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e72.1 (4.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71.4 (3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e72.0 (4.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eValues are mean (SD). TSG\u0026thinsp;=\u0026thinsp;MAP\u0026thinsp;\u0026minus;\u0026thinsp;SVC pressure.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eTSG groups were defined by whether TSG ever fell below 30 mmHg during the clamp period (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 vs TSG\u0026thinsp;\u0026ge;\u0026thinsp;30).T2 represents the worst clamping physiology and is reported as peak SVC pressure (SVC_max) and minimum cerebral rSO₂ (rSO₂_min) observed during clamping; MAP/TSG were not recorded as a standardized paired value at that exact \u0026ldquo;worst\u0026rdquo; moment in all cases and therefore are not shown for T2.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn patients who met protocol criteria (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg), corrective maneuvers were associated with a marked improvement in perfusion surrogates from T1 to T4: mean TSG increased from 24.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8 to 49.1\u0026thinsp;\u0026plusmn;\u0026thinsp;6.4 mmHg (Δ\u0026thinsp;+\u0026thinsp;24.9 mmHg), accompanied by a reduction in SVC pressure (45.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.3 to 25.3\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5 mmHg; Δ\u0026thinsp;\u0026minus;\u0026thinsp;19.7 mmHg) and an increase in cerebral rSO₂ (62.2\u0026thinsp;\u0026plusmn;\u0026thinsp;5.6% to 68.1\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8%; Δ\u0026thinsp;+\u0026thinsp;5.9%). After clamp release (T5), SVC pressure and rSO₂ returned close to baseline in both groups.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eProtocol-triggered venous decompression (blood withdrawal/reinfusion)\u003c/strong\u003e \u003cp\u003eBy protocol, temporary autologous venous blood withdrawal with reinfusion was performed in all patients meeting the trigger criterion (TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg; 89/89, 100%) and in none of those with TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg (0/609, 0%). As this intervention was conditional on TSG status by design, no hypothesis testing was performed and no P value is reported (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eNIRS desaturation and its association with TSG\u003c/h2\u003e \u003cp\u003eClinically significant cerebral desaturation (\u0026ge;\u0026thinsp;20% below baseline\u003cb\u003e)\u003c/b\u003e was observed in 54 patients (7.7%). Of these, 9 patients demonstrated concurrent TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg, indicating overlap between invasive (TSG) and non-invasive (NIRS) indicators of cerebral vulnerability \u003cb\u003e(\u003c/b\u003eFig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eNeurological outcomes\u003c/h2\u003e \u003cp\u003eTransient partial seizures occurred in 6 patients (0.86%) within the first 24 h postoperatively, all resolving without sequelae. Importantly, all seizure events occurred in patients with both TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg and concurrent NIRS desaturation. No patient had persistent neurological deficit documented at ICU discharge.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBox-and-whisker plot comparing ICU stay between patients with TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg and TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg during off-pump bidirectional Glenn. The centre line denotes the median, the box denotes the interquartile range (IQR), and whiskers indicate the range (minimum\u0026ndash;maximum). ICU stay did not differ significantly between groups \u003cb\u003e(\u003c/b\u003eMann\u0026ndash;Whitney U test, P\u0026thinsp;=\u0026thinsp;0.6035\u003cb\u003e).\u003c/b\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBox-and-whisker plot comparing the number of intraoperative inotropes administered in patients with TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg versus TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg during off-pump BDG. The centre line denotes the median and the box denotes the IQR. No significant difference was observed between groups (Mann\u0026ndash;Whitney U, P\u0026thinsp;=\u0026thinsp;0.793).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePoints indicate mean postoperative pulmonary artery pressure (PAP) and error bars indicate SD. PAP was 11.3 (2.6) mm Hg in the TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg group (n\u0026thinsp;=\u0026thinsp;89) and 11.0 (2.3) mm Hg in the TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg group (n\u0026thinsp;=\u0026thinsp;609), with no significant difference between groups (P\u0026thinsp;=\u0026thinsp;0.533).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAll patients with TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg (n\u0026thinsp;=\u0026thinsp;89, 12.8%) received protocol-defined venous withdrawal/reinfusion (89/89, 100%), whereas none of the patients with TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mmHg (n\u0026thinsp;=\u0026thinsp;609, 87.2%) did (0/609, 0%). Because autologous venous withdrawal/reinfusion was a protocol-defined rescue step triggered by TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mmHg, this intervention was performed only in patients meeting that criterion (89/89, 100%) and in none of those who did not (0/609, 0%). No hypothesis testing was performed for this protocol-defined contrast.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eVenn diagram showing the relationship between episodes of transcerebral gradient (TSG; mean arterial pressure minus superior vena cava pressure)\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg and clinically significant cerebral near-infrared spectroscopy (NIRS) desaturation (\u0026ge;\u0026thinsp;20% decrease from baseline) during off-pump bidirectional Glenn in the overall cohort (n\u0026thinsp;=\u0026thinsp;698). TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg occurred in 89 patients and NIRS desaturation in 54 patients, with 9 patients experiencing both events.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe off-pump bidirectional Glenn (BDG) procedure has emerged as a valuable alternative to conventional cardiopulmonary bypass (CPB)-assisted techniques, particularly in paediatric patients with single-ventricle physiology. Avoidance of CPB mitigates systemic inflammatory activation, coagulopathy, transfusion-related complications, and potential cerebral reperfusion injury\u0026mdash;effects that may be amplified in infants and young children [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Nevertheless, temporary superior vena cava (SVC) clamping during BDG introduces unique haemodynamic challenges by obstructing cerebral venous return, increasing SVC/central venous pressure (CVP), and potentially reducing effective cerebral perfusion [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Preservation of cerebral perfusion in this setting is a cornerstone of perioperative neuroprotection, and our study\u0026mdash;reporting outcomes in 698 patients, the largest cohort to date\u0026mdash;supports the feasibility of an integrated anaesthetic strategy targeting a transcerebral gradient (TSG)\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg in combination with near-infrared spectroscopy (NIRS) monitoring to minimise cerebral risk while maintaining favourable perioperative recovery.\u003c/p\u003e \u003cp\u003eTSG, defined as the difference between mean arterial pressure and SVC/CVP, has been used as a pragmatic surrogate for cerebral perfusion pressure during SVC occlusion, with values\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg commonly regarded as a threshold that helps preserve autoregulation and limits venous congestion [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. In our series, 12.8% of patients (n\u0026thinsp;=\u0026thinsp;89) developed intraoperative TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg. These episodes were managed using a standardised algorithm incorporating vasoactive titration (norepinephrine, with escalation to epinephrine and/or vasopressin when required), maintenance of azygos venous drainage, and temporary autologous central venous blood withdrawal with subsequent reinfusion after anastomosis. Importantly, there was no operative mortality, and only six patients (0.85%) experienced transient partial seizures within the first 24 h postoperatively, all resolving without sequelae. Notably, all neurological events occurred in the subset with concomitant TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg and NIRS desaturation, underscoring the clinical relevance of integrating invasive haemodynamic targets with real-time cerebral oxygenation monitoring. These findings extend earlier smaller series by Hoffman et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and Salazar et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], which highlighted the vulnerability to cerebral hypoperfusion during off-pump BDG and the potential value of targeted protective strategies.\u003c/p\u003e \u003cp\u003eCerebral NIRS monitoring has become an important component of paediatric cardiac anaesthesia, providing continuous, non-invasive assessment of cerebral oxygenation and enabling early detection of adverse trends before overt clinical deterioration [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In our cohort, clinically important desaturation (\u0026ge;\u0026thinsp;20% fall from baseline) occurred in 54 patients (7.7%), with 9 cases demonstrating concomitant TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg. This overlap supports the complementary role of NIRS alongside invasive perfusion surrogates and is consistent with prior work demonstrating associations between intraoperative cerebral oximetry and neurological outcomes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. More importantly, protocolised corrective actions\u0026mdash;including haemodynamic optimisation, ventilatory adjustment, haematocrit correction, and preservation of azygos venous drainage\u0026mdash;were effective in restoring cerebral oxygenation and were not associated with permanent neurological injury. Standardising these responses may reduce practice variability and strengthen team-level adherence to neuroprotective goals during SVC clamping.\u003c/p\u003e \u003cp\u003eBroader perioperative outcomes further support the clinical stability of this approach. Despite intraoperative differences in perfusion surrogates, intensive care unit (ICU) stay (1.4 vs 1.2 days), inotrope requirements, and postoperative pulmonary artery pressures did not differ significantly between patients with TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg and those with TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Universal extubation in the operating room (100%) was achieved, consistent with the systemic benefits of avoiding CPB and its inflammatory burden. These findings align with prior reports of reduced morbidity and accelerated recovery in selected off-pump BDG cohorts [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. In addition, routine preservation of azygos venous drainage during the anastomosis may have contributed to favourable neurological outcomes, in keeping with data suggesting improved haemodynamic tolerance when cerebral venous egress is maintained [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe early neurological event rate of 0.85% observed in this study is lower than the 2\u0026ndash;5% range reported in previous off-pump BDG cohorts [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. While this difference may reflect advances in perioperative monitoring and care pathways over time, it also supports the potential value of combining a prespecified TSG target with NIRS-triggered, stepwise interventions. The large sample size strengthens the reproducibility of these observations compared with earlier reports limited by smaller cohorts and heterogeneous thresholds or rescue strategies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Collectively, our findings add to growing evidence that proactive multimodal monitoring and algorithm-based responses can reduce neurological morbidity in this high-risk population.\u003c/p\u003e \u003cp\u003eSeveral limitations should be acknowledged. The retrospective observational design introduces the potential for selection bias, and the absence of randomised comparison precludes causal inference. Furthermore, while early neurological events were systematically captured within 24 h, structured long-term neurodevelopmental follow-up was not performed [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Several limitations should be acknowledged. The retrospective observational design introduces the potential for selection bias, and the absence of a randomized comparator precludes causal inference. Neurological follow-up was limited to early clinical surveillance and clinically triggered testing within the first 24 h; routine EEG or standardized neuroimaging was not performed in all patients. Therefore, subclinical events and longer-term neurodevelopmental outcomes may have been missed, and prospective studies with predefined neurological assessments are warranted. However, 147 patients subsequently returned for Fontan completion at our institution with a median interval of 5 years (range 2\u0026ndash;9 years), and clinical neurological assessments during pre-Fontan evaluation did not identify overt neurological deficits. This observation is reassuring but does not replace standardized neurocognitive testing, and subtle deficits may manifest later. Prospective multicentre studies incorporating predefined neurodevelopmental endpoints are warranted to validate these findings and to refine optimal age-specific thresholds for both TSG and NIRS during off-pump cavopulmonary connection.\u003c/p\u003e \u003cp\u003eHowever, 147 patients subsequently returned for Fontan completion at our institution with a median interval of 5 years (range 2\u0026ndash;9 years), and clinical neurological assessments during pre-Fontan evaluation did not identify overt neurological deficits. This observation is reassuring but does not replace standardised neurocognitive testing, and subtle deficits may manifest later, as highlighted in prior literature [\u003cspan additionalcitationids=\"CR22\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Prospective multicentre studies incorporating predefined neurodevelopmental endpoints are warranted to validate these findings and to refine optimal age-specific thresholds for both TSG and NIRS in off-pump cavopulmonary connection.\u003c/p\u003e \u003cp\u003eIn conclusion, our 698-patient two-centre experience demonstrates that a standardised algorithm targeting TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg, integrated with continuous cerebral NIRS monitoring and stepwise corrective actions, is feasible during off-pump BDG and is associated with low rates of clinically important cerebral desaturation and early neurological events. These data support consideration of integrated TSG\u0026ndash;NIRS protocols as a reproducible framework for cerebral protection during off-pump BDG, while underscoring the need for prospective validation with long-term neurodevelopmental follow-up.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn this large retrospective cohort of 698 pediatric patients undergoing off-pump bidirectional Glenn (BDG) anastomosis, a goal-directed anesthetic strategy targeting a transcerebral gradient (TSG)\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg and integrated with near-infrared spectroscopy (NIRS) monitoring was feasible and was associated with favorable early clinical outcomes. This multimodal approach\u0026mdash;including titrated vasoactive support, maintenance of azygos venous drainage, hematocrit optimization, and protocolized autologous central venous blood withdrawal with reinfusion\u0026mdash;was associated with a very low rate of transient neurological events (0.85%), universal extubation in the operating room, and stable postoperative hemodynamics without operative mortality. Prospective studies incorporating standardized neurodevelopmental follow-up are warranted to confirm generalizability and to refine optimal thresholds for TSG and NIRS-guided interventions. These findings suggest that the incorporation of TSG and NIRS-guided interventions provides a reproducible framework for cerebral protection in high-risk paediatric patients undergoing cavopulmonary connection without cardiopulmonary bypass. While the retrospective design and absence of long-term neurodevelopmental follow-up remain important limitations, our data underscore the potential for this algorithm to serve as a standardized management protocol. Prospective multicenter trials with long-term neurocognitive assessment are warranted to validate these results and further define the role of integrated TSG\u0026ndash;NIRS monitoring in optimizing outcomes after off-pump Glenn procedures.\u003c/p\u003e"},{"header":"Declarations","content":" \u003cp\u003e \u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e \u003cp\u003e This study was approved by the Clinical Research Ethics Committee of Medicana International Istanbul Hospital (Approval: December 2025; File No: 78). Given the retrospective nature of the study and the use of routinely collected clinical data, the requirement for individual informed consent was waived by the ethics committee.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent for publication:\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eCompeting interests:\u003c/h2\u003e \u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e \u003cp\u003eNo funding was received for this study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eİbrahim \u0026Ouml;zg\u0026uuml;r \u0026Ouml;nsel \u0026sup1;; Barış Kırat \u0026sup1;;Mustafa Kemal Avşar \u0026sup2;; Onur Benli \u0026sup2;; Cenap Zeybek \u0026sup3;İ.\u0026Ouml;.\u0026Ouml;. and B.K. contributed to anesthesia planning, intraoperative management, and data collection. M.K.A. and OB designed the study, performed surgical procedures, supervised data analysis, and drafted the initial manuscript. C.Z. contributed to patient follow-up, clinical data acquisition, and interpretation of echocardiographic and hemodynamic findings. OB. assisted with perioperative management, surgical logistics, and data validation. All authors critically revised the manuscript, approved the final version, and agree to be accountable for all aspects of the work.\u003c/p\u003e\u003ch2\u003eAcknowledgements:\u003c/h2\u003e \u003cp\u003eThe authors would like to thank the operating room nurses, anesthesia technicians, and intensive care unit staff for their valuable contributions to the surgical care of the patients.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGlenn WW. Circulatory bypass of the right side of the heart. IV. Shunt between superior vena cava and distal right pulmonary artery; report of clinical application. 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World J Pediatr Congenit Heart Surg. 2020;11(1):39\u0026ndash;48. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/2150135119885890\u003c/span\u003e\u003cspan address=\"10.1177/2150135119885890\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Bidirectional Glenn, cerebral oximetry, near-infrared spectroscopy, off-pump, paediatric anaesthesia, transcerebral gradient","lastPublishedDoi":"10.21203/rs.3.rs-8624939/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8624939/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eOff-pump bidirectional Glenn (BDG) avoids cardiopulmonary bypass (CPB), but superior vena cava (SVC) clamping may compromise cerebral perfusion. We evaluated a goal-directed anaesthetic algorithm integrating mean arterial pressure minus SVC pressure (transcerebral gradient, TSG) with cerebral near-infrared spectroscopy (NIRS).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe conducted a retrospective two-centre cohort study of 698 children undergoing off-pump BDG (2016\u0026ndash;2025). The protocol targeted TSG\u0026thinsp;\u0026ge;\u0026thinsp;30 mm Hg with continuous invasive arterial and SVC pressure monitoring. Bilateral frontal NIRS was monitored continuously; clinically important desaturation was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;20% fall from baseline. Stepwise interventions for TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg and/or NIRS desaturation included vasoactive titration, ventilatory optimisation, maintenance of azygos venous drainage during anastomosis, haematocrit optimisation, and temporary autologous venous blood withdrawal with reinfusion after anastomosis.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThere were no deaths (0%, 95% CI 0\u0026ndash;0.53%), and all patients were extubated in the operating room. TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg occurred in 89/698 patients (12.8%, 95% CI 10.4\u0026ndash;15.5). Cerebral NIRS desaturation occurred in 54/698 (7.7%, 95% CI 5.9\u0026ndash;10.0); 9/54 had concomitant TSG\u0026thinsp;\u0026lt;\u0026thinsp;30 mm Hg. Transient partial seizures occurred in 6/698 (0.86%) within the first 24 h postoperatively, all resolving without sequelae. Mean postoperative pulmonary artery pressure was 11.1 (2.3) mm Hg.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn this large off-pump BDG cohort, a standardised TSG- and NIRS-guided algorithm was feasible and was associated with low rates of cerebral desaturation and early neurological events. Prospective studies with standardised neurodevelopmental follow-up are warranted.\u003c/p\u003e","manuscriptTitle":"Cerebral Protection via Transcerebral Gradient-Guided Strategy in Pediatric Bidirectional Glenn","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-03-03 14:17:54","doi":"10.21203/rs.3.rs-8624939/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-10T07:45:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-08T12:50:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"46248887688558197537431414138567596069","date":"2026-02-26T09:28:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-24T00:40:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"121600960961481897585765861436658773143","date":"2026-02-23T14:38:37+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-23T13:18:33+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-02-13T13:39:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-23T06:20:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-23T06:20:02+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pediatrics","date":"2026-01-17T09:21:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pediatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bped","sideBox":"Learn more about [BMC Pediatrics](http://bmcpediatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bped/default.aspx","title":"BMC Pediatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"28c521fc-631e-4293-99f1-1bb925da3f74","owner":[],"postedDate":"March 3rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-06T08:54:15+00:00","versionOfRecord":[],"versionCreatedAt":"2026-03-03 14:17:54","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8624939","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8624939","identity":"rs-8624939","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}