W.B. Geven

Activation of the inflammatory reaction within minutes after birth in ventilated preterm lambs with neonatal respiratory distress syndrome

To study the activation of the inflammatory reaction within minutes after birth, we measured parameters of inflammation before and immediately after birth. To assess whether respiratory distress syndrome (RDS) or birth itself initiates activation, we compared preterm ventilated lambs with term nonventilated lambs. Preterm lambs were delivered by cesarean section at 132 days gestational age (term 145 days) and were ventilated by conventional ventilation (n = 9). Before clamping the cord, 5, 10 and 15 min after birth, blood was sampled from umbilical catheters. Term lambs (n = 9) were born spontaneously after 140–145 days gestational age. Immediately after birth, a venous umbilical catheter was inserted. Blood was sampled before the first breath and 5, 10, 15 and 20 min after birth while the lamb was breathing spontaneously. Blood was analyzed for AP50 (complement activation), number of polymorphonuclear leukocytes (PMNs) and β-glucuronidase (released from activated PMNs). In preterm lambs, we found a decreased number of PMNs and increased levels of β-glucuronidase already at 5 min after birth. In the term lambs, we found only a short-term mild decrease in PMNs and short-term increase in β-glucuronidase. We conclude that systemic activation of the inflammatory reaction can be found in ventilated preterm lambs with RDS within 5 min after birth. This very early activation is mild, transient and less pronounced in term-born spontaneously breathing lambs compared with preterm, ventilated lambs with RDS.

Recirculation in double lumen catheter veno-venous extracorporeal membrane oxygenation measured by an ultrasound dilution technique.

Recirculation is a limiting factor for oxygen delivery in double lumen catheter veno-venous extracorporeal membrane oxygenation (DLVV-ECMO). This study compares three different methods for the determination of the recirculation fraction during double lumen catheter veno-venous ECMO at ECMO flow rates of 150, 125, 100, 75, and 50 ml/kg.min in nine lambs: (1) an ultrasound dilution method, in which the change in ultrasound velocity in blood after injection of a saline bolus as a marker is used for determination of recirculation; (2) an SvO2 method using real mixed venous blood oxygen saturation, the gold standard, for determination of recirculation fraction; and (3) the CVL method, in which oxygen saturation of a blood sample of the inferior vena cava is considered to represent mixed venous oxygen saturation. In all methods, the recirculation fraction increased with increasing ECMO flow rate. The correlation coefficient between the ultrasound dilution method and the SvO2 method was 0.68 (p < 0.01); mean difference was -2.4% (p = 0.6). Correlation coefficient between the ultrasound dilution method and the CVL method was 0.48 (p < 0.01); mean difference was -18.1% (p < 0.01). The correlation coefficient between the SvO2 method and the CVL method was 0.51 (p < 0.01); mean difference was -15.7% (p < 0.01). The ultrasound dilution method is a useful method for measurement of the recirculation fraction in DLVV-ECMO and is easier to use than the other methods.

Early activation of inflammation and clotting in the preterm lamb with neonatal RDS: Comparison of conventional ventilation and high frequency oscillatory ventilation

In neonatal respiratory distress syndrome activation of inflammation and clotting is demonstrated. High frequency oscillatory ventilation (HFOV) is considered to be less damaging to the human preterm lung, resulting in less activation of inflammation and clotting compared with conventional ventilation (CV). To assess the sequence of events of activation of inflammation and clotting and to compare the impact of HFOV to CV, we ventilated preterm lambs delivered by cesarean section at 132 d gestational age (term 145 d) for 8 h by CV (n = 10) or HFOV (n = 11). Fifteen minutes after birth and at 2-h intervals thereafter blood samples, from umbilical catheters, were analyzed for AP50 (complement activation), number of polymorphonuclear leukocytes, β-glucuronidase, platelet function, activated partial thromboplastin time, thrombin time and thrombin inhibition, and bronchoalveolar lavage fluid was analyzed for elastase, thrombin and protein. We found complement activation, low number of polymorphonuclear leukocytes and high levels of β-glucuronidase already at 15 min after birth. Within 2 to 4 h after birth platelet function deteriorated, activated partial thromboplastin time prolonged, and thrombin inhibition decreased. Activation of inflammation and clotting in the lungs was demonstrated by increased levels of elastase and thrombin in bronchoalveolar lavage fluid. In the HFOV group, AP50 remained significantly higher than in the CV group, reflecting less complement activation, and platelet function analysis remained significantly lower, reflecting better platelet function. We conclude that systemic activation of inflammation can be found in the ventilated preterm lamb with respiratory distress syndrome within 15 min after birth. Afterward, or due to activation of inflammation, clotting is activated. HFOV possibly attenuates activation of inflammation.

Disturbance of cerebral oxygenation and hemodynamics related to the opening of the bypass bridge during Veno-arterial extracorporeal membrane oxygenation

ABSTRACT: The objective of this study was to investigate changes of cerebral oxygenation and hemodynamics related to opening of the bypass bridge during veno-arterial extracorporeal membrane oxygenation (ECMO). Ten newborn infants and 12 piglets were studied during opening of the bridge for 10 and 1 s, respectively. Changes in cerebral concentration of oxyhemoglobin (c O2Hb), deoxyhemoglobin (c HHb), (oxidized-reduced) cytochrome aa3 (c Cyt.aa3), and blood volume (CBV) were continuously measured by near infrared spectropbotometry. Heart rate, arterial O2 saturation (s aO2), and mean arterial blood pressure (MABP) were measured simultaneously. In the piglets, central venous pressure (CVP), intracranial pressure (ICP), and left common carotid artery blood flow (CaBF) were also measured. Opening of the bridge for 10 s in the infants resulted in a significant decrease in MABP, s aO2, and c O2Hb, whereas c HHb increased. CBV did not change significantly. In piglets biphasic changes were observed for MABP, CaBF, c O2Hb, and CBV, showing an initial decrease followed by a smaller increase. c HHb and CVP showed reverse biphasic changes. ICP increased but s aO2 was unchanged. In all cases heart rate and c Cyt.aa3 did not change significantly. Opening of the bridge for 1 s resulted in minor changes in only a few variables. In conclusion, opening of the bridge resulted in a decrease of CBV and cerebral O2 supply due to a decrease of cerebral blood flow, followed by a compensatory increase of cerebral O2 extraction and vasodilatation. The return of oxygenated blood after reclosing resulted in an increase of CBV with overcompensation of cerebral O2 supply.

Hemodynamic changes during opening of the bridge in venoarterial extracorporeal membrane oxygenation

Objective To investigate the cause of the hemodynamic changes occurring during opening of the bridge in venoarterial (VA) extracorporeal membrane oxygenation (ECMO). Design Prospective intervention study in animals. Setting Animal research laboratory of a university medical center. Subjects Eight anesthetized lambs installed on VA-ECMO. Interventions During VA-ECMO the bridge was randomly opened during 1, 2.5, 5, 7.5, 10, and 15 secs at ECMO flow rates of 500, 400, 300, 200, 100, and 50 mL/min. Flows in the ECMO circuit between venous cannula and bridge and bridge and arterial cannula, mean arterial blood pressure, mean left carotid artery blood flow, central venous pressure, superior sagittal sinus pressure, inline mixed venous oxygen saturation, heart rate, and arterial oxygen saturation were measured continuously. Using near infrared spectrophotometry, changes in concentrations of cerebral oxygenated and deoxygenated hemoglobin and cerebral blood volume were also measured. Values during bridge opening were compared with values before opening. The same variables were determined with a roller pump on the bridge with a flow over the bridge at various flow rates. Measurements and Main Results Bridge opening resulted in a change of flow direction between venous cannula and bridge and bridge and arterial cannula. A biphasic response with initial decrease and secondary increase occurred in mean arterial blood pressure and mean left carotid artery blood flow. Central venous pressure, superior sagittal sinus pressure, deoxygenated hemoglobin, and cerebral blood volume increased, whereas cerebral oxygenated hemoglobin decreased. These effects occurred in each combination of ECMO flow rate and opening time. These effects could be abolished by installing a roller pump on the bridge. Conclusions Bridge opening in VA-ECMO resulted in significant cerebral hemodynamic changes caused by an arteriovenous shunt over the bridge. The decreased cerebral perfusion pressure may contribute to the occurrence of cerebral ischemia, and the venous congestion may result in intracranial hemorrhages. These could be prevented by installing a roller pump on the bridge.

High Frequency Oscillatory Ventilation (HFOV) results in less activation of inflammation and cloning compared to Conventional Ventilation (CV) in the preterm lamb with neonatal RDS.

High Frequency Oscillatory Ventilation (HFOV) results in less activation of inflammation and clotting compared to Conventional Ventilation (CV) in the preterm lamb with neonatal RDS

Differences in pressure volume characteristics of excised lungs or premature lambs ventilated with Intermittent Positive Pressure Ventilation(IPPV) or High Frequency Oscillation(HFO).

Differences in pressure volume characteristics of excised lungs of premature lambs ventilated with Intermittent Positive Pressure Ventilation (IPPV) or High Frequency Oscillation (HFO)

HEMODYNAMIC CHANGES DURING BRIDGE OPENING IN VENO-ARTERIAL (VA) ECMO. 316

Fluctuations in cerebral hemodynamics occurred during bridge opening in VA ECMO (Pediatr Res 1995,38:124-9). To investigate the cause of these effects the bridge was opened for 2.5 and 15 s at different flow rates (500 and 50 ml/min) in 8 lambs during VA ECMO. Changes (▵) in mean arterial blood pressure (MABP), central venous pressure (CVP), left common carotic artery blood flow (Qcar), cerebral total hemoglobin concentration (ctHb, measured with near infrared spectrophotometry), intracranial pressure (ICP), flow in the ECMO circuit on the venous side between lamb and bridge (VF), and on the arterial side between bridge and lamb (AF) were measured continuously during 60 s after opening of the bridge and were compared with the mean values in the 30 s preceding the opening. During opening of the bridge changes of flow direction occurred in VF and AF, resulting in a biphasic response of MABP and Qcar and an increase in CVP, ICP, and ctHb (representing cerebral bloodvolume). Values in the table are mean ± SD. These hemodynamic changes during opening of the bridge in VA ECMO, which were independent of ECMO flow rate and opening time duration, may carry a potential risk for intracranial pathology.