Taisuke Okamoto

Preliminary experiment with a newly developed double balloon, double lumen catheter for extracorporeal life support vascular access.

Recently, venovenous extracorporeal life support (VVECLS) using a double lumen catheter has been clinically used to avoid neurologic complications in the treatment of respiratory failure for neonates. However, recirculation, which is a limiting factor for oxygen delivery, still exists, and thus it does not contribute to oxygenation of the patient. We developed a newly designed double lumen catheter with a double balloon (DBDL) catheter for ECLS vascular access and performed two animal preliminary experiments in normal and hypoxic dog models (normal ventilation and one lung ventilation experiments) to investigate whether the DBDL catheter could prevent recirculation and maintain oxygen delivery to systemic circulation. The DBDL catheter (JCT Co., Hiroshima, Japan) of 15 Fr was fabricated from silicone. It consists of two lumens for drainage and return of blood with two balloons (distal and proximal balloons) that prevent oxygenated blood mixing with unoxygenated blood. VVECLS using a DBDL catheter was performed in 13 mongrel dogs (8 dogs for normal ventilation experiment weighing 12.9 ± 1.6 kg [mean ± SD], 5 dogs for one lung ventilation experiment weighing 16.6 ± 2.5 kg [mean ± SD]) under anesthesia in the two experiments. The bypass flow ranged from 10–40 ml/kg per minute in the normal ventilation experiment. VVECLS in the one lung ventilation experiment was performed with maximal bypass flow for 6 hours (ranged from 25.2 ± 8.0–28.3 ± 8.7 ml/kg per minute at balloon inflation and deflation). Recirculation and oxygen transfer of artificial lung with or without balloon inflation during VVECLS were studied. Recirculation decreased with balloon inflation at varied bypass flows during VVECLS in the normal ventilation experiment (varied from 1.5 ± 14.6–12.8 ± 16.7%) and for 6 hours after VVECLS initiation in the one lung ventilation experiment (varied from 12.2 ± 12.2–19.2 ± 6.5 %). In particular, the values at 3 and 6 hours were significantly lower than that of balloon deflation in the one lung ventilation experiment. The difference in O2 content between inlet and outlet in the artificial lung with balloon inflation was significantly higher than that of balloon deflation (varied from 3.7 ± 1.8–4.8 ± 1.9 ml/dl, p < 0.05) at the bypass flow of 10–30 ml/kg per minute in the normal ventilation experiment and at 5 hours after VVECLS initiation in the one lung ventilation experiment (varied from 10.6 ± 1.6–11.7 ± 1.8 ml/dl). The blood gas analysis of systemic circulation with balloon inflation revealed that the values of PaO2 (varied from 83.8 ± 11.4–96.9 ± 23.4 mm Hg) and PaCO2 (37.7 ± 9.2–40.4 ± 11.8 mm Hg) were higher and lower, respectively, compared with balloon deflation. In particular, PaO2 level was significantly higher than that of the preECLS value at the bypass flow of 20–40 ml/kg per minute (varied from 83.8 ± 11.4–96.9 ± 23.4 mm Hg, p < 0.05). In the one lung ventilation experiment, systemic PaO2 and PaCO2 levels at balloon inflation were higher and lower, respectively, compared with balloon deflation during VVECLS for 6 hours. At balloon inflation, the value of PaO2 at 6 hours after VVECLS initiation was significantly higher than that at balloon deflation. A newly designed DBDL catheter for ECLS vascular access successfully reduced recirculation and maintained oxygen delivery to systemic circulation during VVECLS. These results suggest that a high bypass flow may not be necessarily required in terms of oxygen delivery to systemic circulation when the DBDL catheter was used as an ECLS vascular access.

Heparin bonding of the extracorporeal circuit reduces thrombosis during prolonged lung assist in goats.

This study investigated whether an artificial membrane lung of nonmicroporous polyolefin hollow fibers bonded with heparin could prolong venoarterial extracorporeal lung assist (ECLA) with low dose systemic heparin in goats. We compared heparin bonded circuits (Carmeda Bioactive Surface, “HB” group, n = 5) with non heparin bonded circuits (“NHB” group, n = 5) in venoarterial ECLA (V-A ECLA) for 7 days. Activated coagulation time (ACT) was maintained at approximately 130 sec by systemic infusion of small doses of heparin in the HB group, and at 200–230 sec in the NHB group. Thrombus formation was assessed by visual examination of the circuit, and possible cerebral embolization of thrombi was observed from behavioral abnormalities of the animals. The mean heparin dose given during ECLA was 20.4 ± 3.6 U/kg per hr in HB, and 50.9 ± 14.2 U/kg per hr in NHB, significantly less in HB than NHB (p < 0.01). Blood gas changes across the oxygenator, bypass flow rate, platelet aggregation activity, platelet counts, fibrin monomer (FM) test, and antithrombin-III (AT-III) activity did not differ between the two groups. In HB, thrombi were fewer and no abnormal neurologic symptoms were observed during ECLA. Numerous thrombi were observed in all oxygenators with NHB. One NHB goat developed convulsions and cerebral hemorrhage on the 6th day of ECLA. Nonmicroporous polyolefin hollow fibers can be bonded with heparin. An artificial membrane lung constructed of these fibers showed good anticoagulation by decreased thrombus formation with a small dose of infused heparin.

Newborn extracorporeal lung assist using a novel double lumen catheter and a heparin-bonded membrane lung

We report the clinical application of a novel double lumen catheter for veno-venous extracorporeal lung assist (ECLA) and the use of a heparin-bonded hollow fiber membrane lung, in the treatment of newborn respiratory failure. The outer lumen of the double lumen catheter was 14 Fr and was used for blood drainage; while the inner 8 Fr catheter was used for blood return. The double lumen catheter was made of spiral wire reinforced polyurethane, with a wall thickness of 0.25 mm. The hollow fiber membrane was made of non-microporous polyolefin, and was not permeable to water or plasma. We used this system to treat a newborn patient with meconium aspiration syndrome. Heparin was infused continuously at a rate of 18–25 units/kg/h, equal to 1/3 of the usual amount when a non-heparin bonded ECLA system was used and maintaining the activated clotting time near 120 s. Bleeding from cutdown sites was negligible. Only the right internal jugular vein was sacrificed. The patient was successfully weaned from ECLA and appears normal one year following discharge.

INHALED NITRIC OXIDE FOLLOWED BY EXTRACORPOREAL MEMBRANE OXYGENATION IN RESUSCITATING A NEWBORN WITH HYPOXEMIA

In a newborn requiring cardiopulmonary resuscitation because of hypoxemia due to sepsis (oxygenation index > 40), inhalation of nitric oxide (NO) in a concentration of 16p.p.m. improved oxygenation and restored spontaneous circulation. Cannulation for extracorporeal membrane oxygenation (ECMO) then was performed safely under NO inhalation. ECMO was discontinued on day 7, and on day 14 the infant was extubated. During follow‐up examination at 5 months of age no neurological abnormalities were found. This case shows the usefulness of combining inhaled NO and ECMO.

Does veno-arterial bypass without an artificial lung improve the outcome in dogs undergoing cardiac arrest?

We hypothesized that maintaining circulation and blood pressure by veno-arterial bypass (V-A bypass) without oxygenation would improve cardiopulmonary resuscitation (CPR) and survival rates. A total of 32 dogs, divided into four groups, were subjected to normothermic ventricular fibrillation (VF) for 15 min. The method of CPR was the same in the four groups, except for the method and timing of V-A bypass. We attempted to resuscitate the dogs without V-A bypass (control), with V-A bypass not including an artificial lung during VF, with V-A bypass not including an artificial lung during CPR, and with V-A bypass including an artificial lung during CPR. CPR was continued until restoration of spontaneous circulation (ROSC) or for 30 min. Although blood pressure was well maintained, severe hypoxemia was observed during V-A bypass without an artificial lung. The resultant hypoxemia was very detrimental. ROSC was achieved more easily in all dogs in the bypass group with an artificial lung. No significant difference in survival rates was demonstrated among the four groups (P = 0.11). We concluded that V-A bypass without oxygenation does not improve the chances for CPR and outcome after cardiac arrest in dogs. Our results suggest that oxygenation is indispensable in CPR.

Total and prolonged filling of the lungs with Ringer’s solution under extracorporeal lung assist (ECLA) in dogs

Background: Massive alveolar lavage has been used clinically to remove materials accumulated in the alveoli. Recently, filling the lungs with oxygenated perfluorochemical (total liquid ventilation) has been investigated. However, effects of complete and prolonged filling of bilateral lungs with aqueous fluid, such as saline or Ringer’s solution, has not been evaluated, although it is possible to sustain gas exchange without the natural lung by using extracorporeal circulation and an artificial lung (extracorporeal lung assist: ECLA). It is also not known whether the lung can recover gas exchange ability after prolonged fluid filling.

Prophylactic epidural administration of fentanyl for the suppression of tourniquet pain

Severe dull pain on the side of tourniquet application and marked rises in blood pressure and heart rate associated with that pain are often observed even under adequate regional analgesia. The purpose of this study was to evaluate the effect of epidural fentanyl on the suppression of tourniquet pain during orthopedic surgical procedures. Forty-five patients undergoing orthopedic surgery of the lower extremities with a tourniquet were maintained by continuous epidural anesthesia with 2% lidocaine through an epidural indwelling polyethylene catheter (L3–4). The patients were randomly allocated to the following three groups: epidural fentanyl (100μg) (epidural group,n=15); intravenous fentanyl (100μg) (intravenous group,n=15); control (no fentanyl) (control group,n=15). The epidural or intravenous fentanyl was administered at the time of the second lidocaine injection. The severity of tourniquet pain based on the patients level of complaint and the total dose of supplemental analgesics requested in the epidural group were significantly lower than those in the control group. Blood pressure during tourniquet application in the epidural group was more stable than in the other two groups. No severe side-effects were observed in any patient. Prophylactic epidural administration of fentanyl might be useful in the suppression of tourniquet pain.

Extracorporeal lung assist for two cases of severe acute respiratory failure

Mechanical pulmonary ventilation (MY) is routinely used for patients with acute respiratory failure (ARF). High airway pressures are at times required to attain alveolar ventilation according to the lung stiffness. However, Kolobow et al. l 3 have recently warned of the insulting effects of MY on the healthy lung. They suggest that the .upper safety limit of lung inflation should be less than 3 times of the normal tidal volume and/or less than 30 cmH20 of the peak inspiratory pressure (PIP). MY with a high PIP might iatrogenically cause overinflation of the still functioning healthy alveoli in the damaged lungs, and worsen ARF. A PIP of over 50 cmH20 was neeessary for two critically ill patients with ARF during conventional MY, and a lifethreatening barotrauma developed. They were treated with veno-venous extracorporeal bypass with an artificial membrane lung (ML). The PIP was lowered to 3035 cmH2 0 or less by decreasing the tidal volume (YT ) during the bypass, and it resulted in an improvement in the lungs.