Aprotinin in children undergoing repair of congenital heart defects.

BACKGROUND: Aprotinin use in adults is increasing, and its use in children has recently been reported. METHODS: The efficacy of aprotinin in children was tested in 80 children. Patients were in four groups: reoperations (59), neonates (8), extremely cyanotic children (6), and other complex repairs (7). The results were compared with those of 55 control infants and children: reoperations (25), neonates (10), cyanotic (10) and complex (10). Treatment groups were identical in age, sex ratio, cross-clamp time, and bypass time. RESULTS: Patients treated with aprotinin had a significant reduction in chest tube drainage (16.5 +/- 9.8 versus 33.4 +/- 22.1 mL.kg-1.h-1; p < 0.001) and time to skin closure (64.2 +/- 23.7 versus 80.1 +/- 24.6 minutes; p < 0.001). Transfusion requirements were decreased in aprotinin-treated patients 4.2 +/- 3.4 versus 6.7 +/- 5.2 donors; p < 0.001). All of the control patients were exposed to at least one donor, whereas 10/80 (12.5%) of the aprotinin-treated group had no blood use (p < 0.006). There were no cases of renal insufficiency or allergic reactions in children receiving aprotinin. Three patients had thrombotic episodes: 2 superior vena caval problems and a lower extremity deep venous thrombosis. There were 3 cases of mediastinitis in the aprotinin group versus none in control patients (p < 0.05). CONCLUSIONS: We conclude aprotinin is an effective means of reducing bleeding, operating time, and donor exposure in infants and children. An increased rate of thrombosis and possibly mediastinitis are potential problems.

Primate brain tolerance to temporary focal cerebral ischemia during isoflurane- or sodium nitroprusside-induced hypotension.

Isoflurane has properties that suggest it may provide cerebral protection from ischemia. This study compared, in primates, neurologic outcome after a 45-min period of temporary focal ischemia during hypotension induced with either isoflurane or sodium nitroprusside (SNP). Fourteen macaque monkeys were studied. Seven animals received halothane and seven isoflurane anesthesia during surgical preparation. After transorbital exposure of the middle cerebral artery (MCA), in the halothane group, the inspired halothane was reduced to 0.75% and the mean blood pressure (BP) reduced to 50 mmHg by the infusion of SNP. In the isoflurane group, the isoflurane was titrated to reduce mean BP to 50 mmHg. Stable hypotension was maintained for 90 min, which included a 45-min period of MCA occlusion. Monitoring included intraarterial blood pressure, arterial blood gases, EEG, somatosensory evoked potentials (SEP), and temperature. After the procedure the animals were allowed to awaken and were assessed neurologically every 8 h. On the third postoperative day, they were reanesthetized and underwent magnetic resonance imaging (MRI) and SEP recording. Thereafter, they were killed with iv KCl and the brains fixed for neuropathology. All animals survived the surgical procedure, but two animals receiving halothane and none receiving isoflurane died prematurely (P less than 0.2). The SEP disappeared in all animals within 10 min of MCA occlusion and then returned partially or completely. There was no difference between groups in neurologic scores, in the size of the lesion as assessed by MRI (isoflurane 15.7 +/- 6%, halothane/SNP 10.5 +/- 4%), or in the extent or severity of the neuropathologic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

High-frequency oscillation compared with standard ventilation in pulmonary injury model.

Hemorrhagic pulmonary edema was induced by intra-atrial infusion of 0.04--0.1 ml/kg of oleic acid into six anesthetized dogs. Gas exchange and cardiac outputs were then compared at identical mean airway pressures during randomized ventilation with either a volume-cycled ventilator with positive end-expiratory pressure (conventional positive-pressure ventilation, tidal volume 16--21 ml/kg, frequency 15--20 cycles/min) or a variable volume piston pump operating at 15 Hz (high-frequency oscillation). The fractional inspired oxygen concentration was maintained at 0.5 throughout. During 17 data sets matched for intratracheal mean airway pressures over a range of 7.5--27 cmH2O, measurements of systemic arterial pressure, arterial blood gas tensions, thermodilution cardiac outputs, and pulmonary arterial and capillary wedge pressures were identical (P less than 0.05) during ventilation with conventional positive-pressure ventilation and high-frequency oscillation. With both forms of ventilation, arterial oxygen tension progressively improved as mean airway pressure increased. In a shunt model of acute lung injury we were unable to show significant differences in oxygenation or cardiac output when high-frequency oscillation was compared with conventional positive-pressure ventilation with positive end-expiratory pressure at equivalent mean airway pressures.

Vagotomy reverses apnea induced by high-frequency oscillatory ventilation.

Apnea has been observed in both animals and patients during high-frequency oscillatory ventilation. The effects of vagotomy were studied during periods of oscillator-induced apnea in 11 pentobarbital-anesthetized dogs. The animals were intubated and breathing spontaneously. An arterial cannula was inserted for monitoring blood pressure and blood gases. Intratracheal airway pressure was measured, and respiratory activity was assessed using either an intrapleural catheter or esophageal balloon. The dogs then underwent high-frequency ventilation at 15 Hz. Apnea was induced by appropriate selection of volume displacement of the piston pump and the distal airway pressure in eucapnic animals. Segments of right and left vagus nerves were exposed in the neck, bathed in local anesthetic, and transected. Spontaneous ventilation resumed immediately in nine animals and could not be suppressed at the same CO2 partial pressure despite continuation of oscillation. We conclude that the apnea observed during high-frequency ventilation is mediated by active vagal inhibition of central respiratory activity and is usually reversed by vagotomy.

Treatment of RDS by high-frequency oscillatory ventilation: a preliminary report.

The feasibility of high-frequency oscillatory ventilation was investigated in eight neonates with severe RDS. Low-volume, high-frequency flow oscillations were generated by a piston pump and delivered through standard endotracheal tubes. Oscillatory frequencies ranged from 8 to 20 Hz and mean airway pressure from 9 to 20 cm H2O. Heart rate, airway pressures, and arterial blood gases and blood pressure were monitored during both continuous positive pressure ventilation and HFO. During HFO mean PaCO2 was 44.0 +/- 4.8 mm Hg. During CPPV immediately prior to oscillation an FIO2 of 0.66 +/- 0.15 resulted in a PaO2 of 59.6 +/- 17.0 mm Hg. Oxygenation improved during HFO such that a mean FIO2 of only 0.41 +/- 0.11 was needed for similar oxygenation. Improvements in oxygenation correlated directly with increases in mean airway pressure. Based on an animal model the phasic pressure swings during HFO are estimated to be 5 to 7 cm H2O in the trachea, much less than conventional ventilation. We conclude that HFO shows great promise in the support of gas exchange in infants with RDS. The use of small phasic volume and pressure swings should minimize pulmonary barotrauma. HFO should also permit the use of lower inspired oxygen fractions.

Ventilation by high-frequency oscillation.

The effect of applying a high-frequency small-volume sinusoidal oscillation at the airway was investigated in anesthetized apneic beagle dogs (mean wt 11 kg, mean VDphys 6.6 +/- 0.6 ml/kg). Oscillations generated by a piston in a cylinder were transmitter to the lungs through an uncuffed endotracheal tube (4.5 mm ID, 6.0 mm OD), which allowed a substantial leak back through the vocal cords. A bias flow of fresh gas presented inspired air to the midtracheal level. The minimum distal airway pressure (measured at the end of the endotracheal tube) was maintained between 0 and 2 cmH2O. Peak airway pressures were 4-8 cmH2O. The optimal frequency for CO2 elimination was 15 Hz. Using volumes of 1.9 ml/kg (range 1.7-2.3) at this frequency the mean PaCO2 was 33.1 +/- 0.5 Torr. In four dogs breathing 100% O2 the PaO2 was 594 +/- 9 Torr during spontaneous ventilation and 580 +/- 9 Torr after 5 h of uninterrupted oscillation. In four experiments using room air the PaO2 was 95 +/- 5 Torr during spontaneous respiration and 106 +/- 1 Torr after 5 h of oscillation. In an additional seven studies there was no difference in mean cardiac output between oscillation and conventional mechanical ventilation. This study demonstrates that high-frequency small-volume oscillations can maintain gas exchange for many hours presumably by markedly enhancing the diffusivity of gases in the lung.