PCO 2 Gradient Between Inlet and Outlet Blood of Extracorporeal Respiratory Support Is a Reliable Marker of CO 2 Elimination.

Our objective was to assess the relationship between the pre-/post-oxygenator gradient of the partial pressure of carbon dioxide (∆ EC PCO 2 ; dissolved form) and CO 2 elimination under extracorporeal respiratory support. All patients who were treated with veno-venous extracorporeal membrane oxygenation and high-flow extracorporeal CO 2 removal in our intensive care unit over 18 months were included. Pre-/post-oxygenator blood gases were collected every 12 h and CO 2 elimination was calculated for each pair of samples (pre-/post-oxygenator total carbon dioxide content in blood [ ct CO 2 ] × pump flow [extracorporeal pump flow {Q EC }]). The relationship between ∆ EC PCO 2 and CO 2 elimination, as well as the origin of CO 2 removed. Eighteen patients were analyzed (24 oxygenators and 293 datasets). Each additional unit of ∆ EC PCO 2 × Q EC was associated with an increase in CO 2 elimination of 5.2 ml (95% confidence interval [CI], 4.7-5.6 ml; p < 0.001). Each reduction of 1 ml STPD/dl of CO 2 across the oxygenator was associated with a reduction of 0.63 ml STPD/dl (95% CI, 0.60-0.66) of CO 2 combined with water, 0.08 ml STPD/dl (95% CI, 0.07-0.09) of dissolved CO 2 , and 0.29 ml STPD/dl (95% CI, 0.27-0.31) of CO 2 in erythrocytes. The pre-/post-oxygenator PCO 2 gradient under extracorporeal respiratory support is thus linearly associated with CO 2 elimination; however, most of the CO 2 removed comes from combined CO 2 in plasma, generating bicarbonate.

Efficacy and Safety of Early Administration of 4-Factor Prothrombin Complex Concentrate in Patients With Trauma at Risk of Massive Transfusion: The PROCOAG Randomized Clinical Trial.

Importance: Optimal transfusion strategies in traumatic hemorrhage are unknown. Reports suggest a beneficial effect of 4-factor prothrombin complex concentrate (4F-PCC) on blood product consumption. Objective: To investigate the efficacy and safety of 4F-PCC administration in patients at risk of massive transfusion. Design, Setting, and Participants: Double-blind, randomized, placebo-controlled superiority trial in 12 French designated level I trauma centers from December 29, 2017, to August 31, 2021, involving consecutive patients with trauma at risk of massive transfusion. Follow-up was completed on August 31, 2021. Interventions: Intravenous administration of 1 mL/kg of 4F-PCC (25 IU of factor IX/kg) vs 1 mL/kg of saline solution (placebo). Patients, investigators, and data analysts were blinded to treatment assignment. All patients received early ratio-based transfusion (packed red blood cells:fresh frozen plasma ratio of 1:1 to 2:1) and were treated according to European traumatic hemorrhage guidelines. Main Outcomes and Measures: The primary outcome was 24-hour all blood product consumption (efficacy); arterial or venous thromboembolic events were a secondary outcome (safety). Results: Of 4313 patients with the highest trauma level activation, 350 were eligible for emergency inclusion, 327 were randomized, and 324 were analyzed (164 in the 4F-PCC group and 160 in the placebo group). The median (IQR) age of participants was 39 (27-56) years, Injury Severity Score was 36 (26-50 [major trauma]), and admission blood lactate level was 4.6 (2.8-7.4) mmol/L; prehospital arterial systolic blood pressure was less than 90 mm Hg in 179 of 324 patients (59%), 233 patients (73%) were men, and 226 (69%) required expedient hemorrhage control. There was no statistically or clinically significant between-group difference in median (IQR) total 24-hour blood product consumption (12 [5-19] U in the 4F-PCC group vs 11 [6-19] U in the placebo group; absolute difference, 0.2 U [95% CI, -2.99 to 3.33]; P = .72). In the 4F-PCC group, 56 patients (35%) presented with at least 1 thromboembolic event vs 37 patients (24%) in the placebo group (absolute difference, 11% [95% CI, 1%-21%]; relative risk, 1.48 [95% CI, 1.04-2.10]; P = .03). Conclusions and Relevance: Among patients with trauma at risk of massive transfusion, there was no significant reduction of 24-hour blood product consumption after administration of 4F-PCC, but thromboembolic events were more common. These findings do not support systematic use of 4F-PCC in patients at risk of massive transfusion. Trial Registration: ClinicalTrials.gov Identifier: NCT03218722.

Performance of the decarboxylation index to predict CO2 removal and minute ventilation reduction under extracorporeal respiratory support.

BACKGROUND: The aim of this study was to assess the interdependence of extracorporeal blood flow (Qec) and gas flow (GF) in predicting CO2 removal and reduction of minute mechanical ventilation under extracorporeal respiratory support. METHODS: All patients who benefited from V-V ECMO and high-flow ECCO2 R in our intensive care unit over a period of 18 months were included. CO2 removal was calculated from inlet/outlet blood port gases during the first 7 days of oxygenator use. The relationship between the Qec × GF product (named decarboxylation index and expressed in L2 /min2 ) and CO2 removal or expired minute mechanical ventilation reduction (EC MV ratio) was studied using linear regression models. RESULTS: Eighteen patients were analyzed, corresponding to 24 oxygenators and 261 datasets. CO2 removal was 393 ml/min (IQR, 310-526) for 1.8 m2 oxygenators and 179 ml/min (IQR, 165-235) for 1.3 m2 oxygenators. The decarboxylation index was associated linearly with CO2 removal (R2  = 0.62 and R2  = 0.77 for the two oxygenators, respectively) and EC MV ratio (R2  = 0.72 and R2  = 0.62, respectively). The 20L2 /min2 value (considering Qec = 2 L/min and GF = 10 L/min) was associated with an EC MV ratio between 61% and 29% for 1.8 m2 oxygenators, and between 62% and 38% for 1.3 m2 oxygenators. CONCLUSION: The decarboxylation index is a simple parameter to predict CO2 removal and EC MV ratio under extracorporeal respiratory support.

Mathematical modelling of oxygenation under veno-venous ECMO configuration using either a femoral or a bicaval drainage.

BACKGROUND: The bicaval drainage under veno-venous extracorporeal membrane oxygenation (VV ECMO) was compared in present experimental study to the inferior caval drainage in terms of systemic oxygenation. METHOD: Two mathematical models were built to simulate the inferior vena cava-to-right atrium (IVC → RA) route and the bicaval drainage-to-right atrium return (IVC + SVC → RA) route using the following parameters: cardiac output (QC), IVC flow/QC ratio, venous oxygen saturation, extracorporeal pump flow (QEC), and pulmonary shunt (PULM-Shunt) to obtain pulmonary artery oxygen saturation (SPAO2) and systemic blood oxygen saturation (SaO2). RESULTS: With the IVC → RA route, SPAO2 and SaO2 increased linearly with QEC/QC until the threshold of the IVC flow/QC ratio, beyond which the increase in SPAO2 reached a plateau. With the IVC + SVC → RA route, SPAO2 and SaO2 increased linearly with QEC/QC until 100% with QEC/QC = 1. The difference in required QEC/QC between the two routes was all the higher as SaO2 target or PULM-Shunt were high, and occurred all the earlier as PULM-Shunt were high. The required QEC between the two routes could differ from 1.0 L/min (QC = 5 L/min) to 1.5 L/min (QC = 8 L/min) for SaO2 target = 90%. Corresponding differences of QEC for SaO2 target = 94% were 4.7 L/min and 7.9 L/min, respectively. CONCLUSION: Bicaval drainage under ECMO via the IVC + SVC → RA route gave a superior systemic oxygenation performance when both QEC/QC and pulmonary shunt were high. The VV-V ECMO configuration (IVC + SVC → RA route) might be an attractive rescue strategy in case of refractory hypoxaemia under VV ECMO.

Structural recirculation and refractory hypoxemia under femoro-jugular veno-venous extracorporeal membrane oxygenation.

The performance of each veno-venous extracorporeal membrane oxygenation (vv-ECMO) configuration is determined by the anatomic context and cannula position. A mathematical model was built considering bicaval specificities to simulate femoro-jugular configuration. The main parameters to define were cardiac output (QC ), blood flow in the superior vena cava (QSVC ), extracorporeal pump flow (QEC ), and pulmonary shunt (kS-PULM ). The obtained variables were extracorporeal flow ratio in the superior vena cava (EFRSVC  = QEC /[QEC  + QSVC ]), recirculation coefficient (R), effective extracorporeal pump flow (Qeff-EC  = [1 - R] × QEC ), Qeff-EC /QC ratio, and arterial blood oxygen saturation (SaO2 ). EFRSVC increased logarithmically when QEC increased. High QC or high QSVC /QC decreased EFRSVC (range, 68%-85% for QEC of 5 L/min). R also increased following a logarithmic shape when QEC increased. The R rise was earlier and higher for low QC and high QSVC /QC (range, 12%-49% for QEC of 5 L/min). The Qeff-EC /QC ratio (between 0 and 1) was equal to EFRSVC for moderate and high QEC . The Qeff-EC /QC ratio presented the same logarithmic profile when QEC increased, reaching a plateau (range, 0.67-0.91 for QEC /QC  = 1; range, 0.75-0.94 for QEC /QC  = 1.5). The Qeff-EC /QC ratio was linearly associated with SaO2 for a given pulmonary shunt. SaO2  < 90% was observed when the pulmonary shunt was high (Qeff-EC /QC  ≤ 0.7 with kS-PULM  = 0.7 or Qeff-EC /QC  ≤ 0.8 with kS-PULM  = 0.8). Femoro-jugular vv-ECMO generates a systematic structural recirculation that gradually increases with QEC . EFRSVC determines the Qeff-EC /QC ratio, and thereby oxygen delivery and the superior cava shunt. EFRSVC cannot exceed a limit value, explaining refractory hypoxemia in extreme situations.