Intratracheal pulmonary ventilation in a rabbit lung injury model: continuous airway pressure monitoring and gas exchange efficacy.

OBJECTIVES: To compare carinal pressures vs. proximal airway pressures, and gas exchange efficacy with a constant minute volume, in lung-injured rabbits during conventional mechanical ventilation (CMV) and intratracheal pulmonary ventilation (ITPV); and to evaluate performance of a prototype ITPV gas delivery and continuous airway pressure monitoring system. DESIGN: Prospective controlled study. SETTING: Animal research laboratory at a teaching hospital. SUBJECTS: Sixteen adult female rabbits. INTERVENTIONS: Anesthetized rabbits were tracheostomized with a multilumen endotracheal tube. Anesthesia and muscle relaxation were maintained continuously throughout the study. Proximal airway pressures and carinal pressures were recorded continuously. The injection port of the multilumen endotracheal tube was used for the carinal pressure monitoring. To prevent obstruction of the port, it was flushed with oxygen at a rate of 11 mL/min. CMV was initiated with a pressure-limited, time-cycled ventilator set at an FiO2 of 1.0 and at a flow of 1.0 L/kg/min. The pressure limit of the ventilator was effectively disabled. A normal baseline for arterial blood gases was achieved by adjusting the inspiratory/expiratory time ratios. ITPV was established using a flow of 1.0 L/kg/min through a reverse thrust catheter, at the same baseline and inspiratory/expiratory ratio. Carinal positive end-expiratory pressure was maintained at a constant value of 2 cm H2O by adjusting the expiratory resistance of the ventilator circuit Lung injury was achieved over a 30-min period by three normal saline lavages of 5 mL/kg each. After lung injury, all animals were consecutively ventilated for 1 hr with CMV, for 1 hr with ITPV, and again for 1 hr with CMV. Six rabbits were ventilated at 30 breaths/min (group 1), and ten rabbits were ventilated at 80 breaths/min (group 2). Four rabbits in group 2 were subjected, 1 hr after return to CMV from ITPV, to another session of ITPV, with positive end-expiratory pressure gradually being increased to 4, 6, and 8 cm H2O for 15 mins each. RESULTS: No significant differences were observed in carinal peak inspiratory pressure between CMV and ITPV modes, at both low and high frequencies of breathing, indicating that the inspired tidal volume remained constant during both modes of ventilation. Significant gradients were noted between proximal airway and carinal peak inspiratory pressure during ITPV but not during CMV. Initiation of ITPV, at a flow of 1.0 L/kg/min, required an increase in the ventilator expiratory resistance to maintain a constant level of positive end-expiratory pressure (2 cm H2O) as measured at the carina. During ITPV, the PaCO2 was significantly reduced by 20% at 30 breaths/min (p < .05) and by 22% at 90 breaths/min (p < .01), compared with CMV. Arterial oxygenation was significantly enhanced with a positive end-expiratory pressure of 6 and 8 cm H2O (p < .05 and .001, respectively), compared with a positive end-expiratory pressure of 2 cm H2O during ITPV. All components of the new prototype gas delivery and airway pressure monitoring system functioned without failure, at least for 3 hrs of the CMV, ITPV, and CMV trials. CONCLUSIONS: ITPV in saline-lavaged, lung-injured rabbits at breathing frequencies of 30 and 80 breaths/min, compared with CMV at the same minute ventilation, can improve CO2 exchange. During ITPV, significant pressure gradients can develop between carinal and proximal airway pressures. Continuous carinal pressure monitoring is therefore necessary for the safe clinical application of ITPV. Reliable carinal pressure monitoring can be achieved by adding a small bias flow through the carinal pressure monitoring port. Although ITPV can remove CO2 from injured lungs efficiently, simultaneous addition of positive end-expiratory pressure can further improve arterial oxygenation.

Oxygen-carrying capacity during 10 hours of hypercapnia in ventilated dogs.

OBJECTIVE: To test if a relatively long-term exogenous hypercapnia, equivalent to those maintained during permissive hypercapnia, can persistently increase oxygen-carrying capacity in ventilated dogs. DESIGN: Prospective study. SETTING: Research laboratory in a hospital. SUBJECTS: Six mongrel dogs (3 males; 3 females). INTERVENTIONS: The dogs were anesthetized (30 mg/kg pentobarbital, i.v.), intubated, and cannulated in one femoral artery, one femoral vein, and the right jugular vein. The mean arterial blood pressure, heart rate, and mean pulmonary artery pressure were continuously recorded. Anesthesia, fluid balance, and normothermia were maintained. Arterial hypercapnia was generated by the addition of 60 torr dry CO2 (8 kPa) to the inspired air for 10 hrs, continuously. All subjects were paralyzed (vecuronium bromide) and ventilated with room air, while the ventilator settings were kept constant. MEASUREMENTS AND MAIN RESULTS: Arterial and venous gas exchange profiles, hemoglobin concentration, oxygen saturation, oxygen content, cardiac output, and oxygen consumption were determined, before, during, and after 10 hrs of hypercapnia, periodically. Both hemoglobin concentration and oxygen content were gradually increased during hypercapnia and reached significant levels at 8 and 10 hrs of hypercapnia, respectively. These increases continued up to 2 hrs after termination of hypercapnia. The PaO2/FIO2, as an index of arterial oxygenation, was significantly increased during the first 3 hrs of hypercapnia and then remained at the normoxic level up to 10 hrs of hypercapnia. No significant changes occurred in the mean arterial blood pressure and oxygen consumption. The heart rate and cardiac output were significantly reduced at 4 and 8 hrs of hypercapnia, respectively. The mean pulmonary artery pressure was increased throughout the hypercapnic trial. CONCLUSIONS: A relatively long-term exogenous hypercapnia can significantly increase oxygen-carrying capacity in normal ventilated dogs. Whether this effect can occur during permissive hypercapnia because of controlled ventilation in patients warrants investigation.

The effect of norepinephrine infusion on oxygen delivery and consumption in the canine model.

Norepinephrine (NE) is used clinically to increase oxygen delivery (DO2) by increasing cardiac output (CO). The rate of administration of NE is usually based on frequent measurements of blood pressure (BP) and infrequent measurements of CO with little regard for oxygen delivery or consumption dynamics. Although the ultimate goal of an inotropic drug is to increase DO2 in excess of metabolic requirements (VO2), the effect of NE on the DO2/VO2 ratio has not been previously studied. In the present investigation, healthy anesthetized dogs were infused with various doses of intravenous NE. These dosages were chosen to span the range used clinically. NE administration caused a significant primary increase in VO2 which was dose dependent (P < 0.001). A similar dose-dependent increase in DO2 was observed (P < 0.001). However, the increase in DO2 minimally exceeded the increase in VO2 at lower doses of NE and the relative increase in VO2 exceeded the change in DO2 at a dose of 0.04 microgram/kg/min. Minimal advantage to oxygen utilization physiology at low doses of NE and a potential deleterious effect at a dose of 0.04 microgram/kg/min were observed, therefore, despite associated increases in mean systemic blood pressure. The effectiveness of NE administration could be most effectively monitored by the mixed venous oxygen saturation (SVO2), rather than by intermittent assessment of BP, CO, or DO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Rescue from pediatric ECMO with prolonged hybrid intratracheal pulmonary ventilation. A technique for reducing dead space ventilation and preventing ventilator induced lung injury.

Hybrid intratracheal pulmonary ventilation (h-ITPV) is a continuous flow ventilatory technique that uses a "reverse thruster" catheter to redirect the flow of gas away from the carina. We report here the use of h-ITPV in a pediatric patient with acute sickle cell chest syndrome who required venoarterial ECMO support because of refractory hypoxemic respiratory failure. Her ECMO course was complicated by air leaks, coagulopathy, cardiac tamponade, and necrotizing tracheobronchitis. She could be weaned from ECMO only by maintaining high pressure conventional ventilatory support. To prevent ventilator induced barotrauma, we initiated h-ITPV and weaned her from ECMO bypass. After 12 days of h-ITPV, with tidal volumes of 2-3 ml/kg at carinal peak inspiratory pressures of 25-30 cm H2O, the air leaks ceased and h-ITPV was discontinued. Dead space ventilation fraction (VD/VT) as low as 0.29 was achieved with this technique. Post-h-ITPV bronchoscopy displayed a dramatic resolution of the necrotizing tracheobronchitis. The patient survived and was discharged from the hospital. We conclude that the use of hybrid ITPV may facilitate weaning from ECMO to low pressure conventional ventilation and prevent the development of pulmonary barotrauma.

A heparin-coated circuit reduces complement activation and the release of leukocyte inflammatory mediators during extracorporeal circulation in a rabbit.

Heparin coating modifies complement activation during extracorporeal circulation much more effectively than systemically administered heparin. This rabbit study was undertaken to address possible mechanisms responsible for this difference. We evaluated the effect of heparin coating on complement activation and subsequently the release of leukocyte inflammatory mediators during extracorporeal circulation through a simplified circuit. We found in the heparin-coated group a significantly reduced complement hemolytic activity (CH50), remaining higher leukocyte numbers, significantly decreased release of beta-glucuronidase, and most strikingly a complete prevention of tumor necrosis factor (TNF) formation. The significantly reduced CH50 activity in the heparin-coated groups indicates the reduction of one or more native classical complement products. This could be explained by the absorption of complement components by the circuit, which results in reduced activity of the complement cascade. We conclude therefore that heparin coating reduces complement activation and consequently reduces the release of leukocyte inflammatory mediators.

Prolonged extracorporeal circulation without heparin. Evaluation of the Medtronic Minimax oxygenator.

Bleeding remains the most common complication of prolonged extracorporeal life support (ECLS). This study evaluated the Medtronic Minimax (Annaheim, CA) microporous oxygenator with the Carmeda Bio Active (heparin bonded) Surface (Stockholm, Sweden) for use in prolonged neonatal ECLS. Eight adult sheep were maintained on venovenous extracorporeal circulation (ECC) for a period of 4 days without systemic heparin. After 4 days of venovenous ECC without anticoagulation, there was no evidence of significant bleeding, circuit thrombosis, or systemic embolism. Gas exchange, hydrodynamic performance, coagulation, and biocompatibility studies suggest that the Minimax is safe and reliable for short-term or long-term ECLS in neonates.

Oxygen kinetics in experimental sepsis.

Systemic oxygen delivery (DO2) is normally four to five times higher than oxygen consumption (VO2), and VO2 is independent of DO2. If DO2 is decreased to less than twice VO2, a state of anaerobic metabolism and supply dependency occurs. Some authors have reported that this biphasic relationship is altered in the adult respiratory distress syndrome or sepsis to a condition of continuous supply dependency. If that were true, it would affect both our understanding and management of metabolism during sepsis. Therefore we measured VO2 and DO2 in a dog peritonitis model. DO2 was regulated with controlled pericardial tamponade. During sepsis VO2 increased 28% from a mean baseline of 5.6 to 7.3 cc O2/kg/min (p less than 0.005). As progressive cardiac tamponade was applied during sepsis, the DO2/VO2 ratio fell. When the DO2/VO2 ratio was greater than 2.4, VO2 remained independent of DO2. At DO2/VO2 ratios less than 2.4, VO2 was dependent on the level of DO2, and it diminished rapidly as DO2 decreased. Oxygen saturation in mixed venous blood (SvO2) consistently reflected the DO2/VO2 ratio in a fashion similar to that in normal dogs. A ratio of DO2/VO2 of 2.4 corresponded with an SvO2 of 42% +/- 12%, which was identified as a statistically significant critical SvO2 that marked onset of VO2 supply dependence. In this dog septic model, VO2 is independent of DO2 when DO2 is adequate. A state of continuous supply dependency does not exist. SvO2 reflects the status of the DO2/VO2 relationship in the septic state.

Prophylactic administration of tranexamic acid preserves platelet numbers during extracorporeal circulation in rabbits.

Neonatal extracorporeal life support is associated with platelet consumption and hemostatic disorders. This study in rabbits was undertaken to evaluate the effect of heparin coating and of the plasminogen and plasmin inhibitor, tranexamic acid on platelet consumption during extracorporeal circulation. Fibrinogen consumption was prevented by heparin coating, but platelet consumption was only prevented after the prophylactic administration of tranexamic acid. The authors concluded that inhibition of the fibrinolytic system had a specific effect on preserving platelet numbers, rather than improving the thromboresistance of the artificial surface. The main advantage of a heparin coating is the anticoagulant activity of the surface. Thus systemic heparinization can be reduced or omitted.

[Hemodynamic adaptation during extracorporeal perfusion and arteriovenous extracorporeal CO2 removal]. / Hämodynamische Adaptation während extrakorporaler Perfusion und Arteriovenösem ECCO2-R.

During an animal study using five bastard dogs the hemodynamic relations during extracorporeal perfusion with an arteriovenous circuit and extracorporeal CO2 removal (ECCO2-R) were analyzed. We utilised a prototype circuit (Promed, West-Germany) which is by diminution and using silicon rubber adapted to the application in newborn. A silicon lung (Scimed, 0.8 m2, ECCO2-R) was used in the circuit. During the six hours perfusion period a main arterial blood pressure of 83 +/- 17 mmHg and an extracorporeal blood flow of 412 +/- 56 ml/min was found using arteriovenous perfusion via the femoral artery and vein. We found a statistical significant correlation (r = 0.66) between the main arterial blood pressure and the extracorporeal blood flow. Further more there was a significant correlation between the arterial PCO2 and the blood flow through membrane lung (r = 0.81). In conclusion our animal experiments approved the possibility of hemodynamic adaptation to an arteriovenous circuit as well as effectiveness of CO2 removal via such circuit.

Laboratory evaluation of a double lumen catheter for venovenous neonatal ECMO.

The authors designed and tested a 14F outside diameter thin-walled double lumen catheter (DLC) for neonatal venovenous (VV) extracorporeal membrane oxygenation (ECMO). In vitro tests with water and dye solution showed capacity of the drainage lumen was 1,096 ml/min at 100 cm siphon, and pressure drop across the perfusion lumen was 300 mmHg at 500 ml/min flow. Recirculation at 500 ml/min flow ranged from 5 to 29%, depending upon simulated cardiac output. The highest serum hemoglobin during 12 hour 400 ml/min flow VV bypass in five dogs was 49 mg/dl. Typical oxygen transport in four dogs was 25 cc/min at 400 ml/min flow. This catheter is well suited for clinical VV ECMO in neonates.

Evaluation of Duraflo II heparin coating in prolonged extracorporeal membrane oxygenation.

Adult sized extracorporeal membrane oxygenation circuits were coated with Duraflo II chemical heparin bonding by Baxter-Bentley Laboratories. Five sheep were maintained on venovenous extracorporeal circulation for four days with no systemic anticoagulation. There was no bleeding, no major thrombosis in the circuits, and no significant emboli after 4 days of extracorporeal circulation without anti-coagulation.