Plasma colloid osmotic pressure in healthy infants.

BACKGROUND: The plasma colloid osmotic pressure (COP) plays a major role in transcapillary fluid balance. There is no information on plasma COP of healthy infants beyond the first post-natal week. The normal COP in healthy adult subjects (25 mmHg) is currently also applied as a reference value for healthy infants. This study was designed to test whether plasma COP values in healthy infants are the same as those in normal adults. METHODS: Plasma COP was measured in 37 male and female healthy infants from 1 to 11 months old. For this purpose, 1 ml blood was collected during the patient's regularly scheduled visit if the patient required any type of blood test for routine laboratory analyses. RESULTS: Plasma COP levels correlated slightly with increasing age from 1 to 9 months old (linear regression analysis; r2 = 0.1, P < 0.049). We found no correlation between plasma COP and body weight at the same age (r2 = 0.05, P = 0.155). The mean and standard deviation of COP in all infants was 25.1 +/- 2.6 mmHg, which is almost identical to an average COP of 25 mmHg in healthy adult subjects. Arbitrary division of the infants into three different age groups (1-3 months [n = 11], 5-8 months [n = 13] and 9-11 months [n = 13]) showed an average increase of approximately 2 mmHg in COP of 9-month-old to 11-month-old infants, compared with 1-month-old to 3-month-old infants (one-way analysis of variance; P = 0.26). There was no gender difference in the COP level (unpaired t-test), with an average of 25.1 +/- 2.4 mmHg in 19 male infants compared with 25.2 +/- 2.9 in 18 female infants. The 95% confidence interval for COP in both male and female infants (n = 37) was between 24.3 to 26.0 mmHg, ranging from 19.5 to 30.3 mmHg, with a median value of 25.2 mmHg. CONCLUSIONS: The data accept the null hypothesis that the COP range in infants younger than 1 year old is similar to those observed in adult subjects. Our observations, compared with previously reported neonatal COP values, suggest that there is a sharp increase in COP within the first months after birth.

Effects of arteriovenous extracorporeal therapy on hemodynamic stability, ventilation, and oxygenation in normal lambs.

OBJECTIVE: To evaluate hemodynamic stability and gas exchange in a neonatal animal model of pumpless arteriovenous extracorporeal membrane oxygenation (AV-ECMO) with extracorporeal shunt flow of up to 15% of cardiac output during variable ventilation and oxygenation. DESIGN: Prospective study. SETTING: Research laboratory in a hospital. SUBJECTS: Seven lambs (5.5 +/- 0.6 kg, mean +/- sd). INTERVENTIONS: The lambs initially were anesthetized by 50 mg/kg ketamine intravenously. After tracheostomy, the lambs were mechanically ventilated and paralyzed by using 1 mg/kg vecuronium bromide followed by 0.1 mg.kg(-1).hr(-1). One femoral vein was cannulated with a pulmonary artery flotation catheter and used for cardiac output and pulmonary artery pressure measurements. A femoral artery was cannulated for measuring mean arterial blood pressure, measuring heart rate, and blood sampling for gas exchange analyses. Finally, the right internal jugular vein and carotid artery were cannulated and used for the AV-ECMO. Normothermia (38 +/- 0.5 degrees C), fluid balance (5 mL.kg(-1).hr(-1) normal saline), and anesthesia (5 mg.kg(-1).hr(-1), intravenous ketamine) were maintained. Ventilator settings were adjusted to establish a baseline Paco2 (25-35 mm Hg) at an Fio2 of 0.4. The AV-ECMO circuit was established by using a hollow fiber oxygenator, primed with maternal sheep blood (150-200 mL). MEASUREMENTS AND MAIN RESULTS: The physiologic effects of the AV-ECMO shunt were evaluated at 15, 25, and 40 mL.kg(-1).hr(-1) ECMO flow, corresponding roughly to 4%, 8%, and 15% of the cardiac output values. The baseline minute volume was maintained during stepwise increases in arteriovenous shunt. A significant increase in endogenous cardiac output occurred at arteriovenous shunt of 25 and 40 mL.kg(-1).hr(-1) (analysis of variance followed by Tukey-Kramer multiple comparisons test), which was attributed to a significant increase of 30% in the heart rate. Effective cardiac output (difference between the thermodilution value and the AV-ECMO flow rate) and mean arterial blood pressure were not significantly changed. CO2 removal, measured at 15% arteriovenous shunt, was significantly increased with decreasing ventilation to 25% and 50% of the baseline (analysis of variance and Tukey-Kramer test). Oxygenation through the membrane was measured after reducing inspired Fio2 from 0.4 to 0.21, 0.15, and 0.10 with 15% arteriovenous shunt and baseline minute ventilation. Oxygen delivery by the oxygenator was significantly increased at Fio2 of 0.10, providing a maximum of 19.5% of the total oxygen consumption at an arterial hemoglobin-oxygen saturation of 60%. CONCLUSIONS: Healthy lambs are capable of maintaining effective cardiac output in the presence of moderate arteriovenous shunts (15%). AV-ECMO may provide efficient ventilatory support in the neonatal population with hypercapnia. The amount of oxygen delivery with AV-ECMO depends on arterial desaturation.

Intratracheal pulmonary ventilation versus conventional mechanical ventilation: continuous carinal pressure monitoring at low and high flows and frequencies.

We continuously measured proximal and carinal pressures at low and high flow rates and frequencies during conventional mechanical ventilation (CMV) and intratracheal pulmonary ventilation (ITPV), using an artificial lung. The proximal peak inspiratory pressure (PIP), carinal PIP, proximal positive end expiratory pressure (PEEP), and carinal PEEP, or negative end expiratory pressure (NEEP), were measured during simulated CMV and ITPV. Two levels of frequency (30 and 90 per min) and two gas flow rates (3 and 6 L/min) were examined, in both dry and humid states (four combinations of gas flow and frequency at each state). The gas flow and inspiratory time were held constant throughout the CMV and ITPV trials. Humidification of the ventilatory circuit during ITPV prevented the accurate measurement of carinal pressures. This problem was solved by introducing a continuous "bias flow" of 11 ml/min into the pressure monitoring line. A combination of low gas flow and low frequency with CMV showed no significant differences between the proximal and carinal PIP, as well as the proximal and carinal PEEP. The same combination with ITPV, however, resulted in a significantly lower carinal PIP and PEEP, compared to proximal PIP and PEEP. Carinal PIP and PEEP during ITPV were also significantly lower than those observed during CMV with a low flow and low frequency rates. During both CMV and ITPV, using a combination of a high flow rate with a high breathing frequency, carinal PIPs were significantly lower than proximal PIPs. ITPV, however, generated much larger differences between proximal and carinal PIPs than the CMV. A significant NEEP was generated at the carinal level during ITPV with high flow rates, both with high and low frequencies. The NEEP did not occur with a low gas flow, in combination with either a low frequency or a high frequency. The "bias flow" had no significant effect on carinal pressures. In conclusion, ITPV, compared with CMV, generates a significantly lower carinal PIP, but it may also generate carinal NEEP. For safety reasons, therefore, it is essential to monitor carinal pressures continuously in patients treated with ITPV.

Insensible water loss during extracorporeal membrane oxygenation: an in vitro study.

To measure insensible fluid loss from silicone membrane oxygenators during extracorporeal membrane oxygenation (ECMO), an in vitro system was used. A standard neonatal ECMO circuit (Avecor) was connected to a noncompliant reservoir, which was then primed with normal saline. The experiment was conducted by using two silicone oxygenators (Avecor 0.4 and 0.8 m2), three gas flow rates (0.5, 1.0, and 2.0 L/min) (sweep), and two fluid flow rates (200 and 400 ml/min). Two methods were used to measure the water loss. One method was to replace the water to the noncompliant circuit by using a calibrated burette, and the other method was to collect condensed water after cooling the postmembrane sweep gas to 0 degrees C. The influence of the amount of sweep, fluid flow rate, size of membrane, and inlet and outlet sweep gas temperatures on measured water loss was statistically determined. The amount of water loss correlated with sweep (r2 = 0.81; p<0.00001) but was not related to the fluid flow rate, membrane size, or inlet and outlet sweep gas temperature. The average daily fluid loss measured with replacement and collection methods for each liter of sweep per minute were 72.0+/-12.6 and 62.3+/-10.0 ml, respectively. This information may be applied to clinical practice to accurately manage fluid balance in the sick neonate on ECMO.

Effect of hypothermia on ventilation in anesthetized, spontaneously breathing rats: theoretical implications for mechanical ventilation.

OBJECTIVE: To test if hypothermia, induced by a sustained pentobarbital anesthesia, in rats can reduce ventilatory demands without compromising pulmonary gas-exchange efficiency. DESIGN: Prospective study. SETTING: Research laboratory in a hospital. SUBJECTS: One group of 11 female Sprague Dawley rats. INTERVENTIONS: The rats were anesthetized with 45 mg/kg pentobarbital, tracheostomized and intubated; their femoral veins and arteries were cannulated. After surgery, anesthesia and fluid balance were maintained (10 mg/kg per h pentobarbital, and 5 ml/kg per h saline, i.v.). Rectal temperature, mean arterial blood pressure (MAP), and heart rate (HR) were continuously monitored. The respiratory variables and gas-exchange profiles were determined at 38 degrees C (normothermia), and during stepwise hypothermia at 37, 35, 33, 31 and 29 degrees C. The arterial pressure of carbon dioxide (PaCO2), pH and arterial pressure of oxygen (PaO2) during hypothermia were corrected at body temperature. MEASUREMENTS AND RESULTS: Graded systemic hypothermia, with maintained anesthesia, produced a strong correlation between reduction in the respiratory frequency and rectal temperature (r2 = 0.55; p < 0.0001; n = 66). The minute volume was significantly reduced, starting at 35 degrees C, without significant changes in the tidal volume (repeated measures of analyses of variance followed by Dunnett multiple comparisons test). No significant changes occurred in the PaCO2, pH, PaO2, hemoglobin oxygen saturation, the calculated arterial oxygen content and estimated alveolar-arterial oxygen difference during mild hypothermia (37-33 degrees C). The PaO2, however, was significantly reduced below 31 degrees C. The MAP remained stable at different levels of hypothermia, whereas HR was significantly reduced below 33 degrees C. CONCLUSIONS: Mild hypothermia in rats, induced by a sustained pentobarbital anesthesia, reduces ventilation without compromising arterial oxygenation or acid-base balance, as measured at body temperature. Theoretically, our observations in spontaneously breathing rats imply that a combination of mild hypothermia with anesthesia could be safely utilized to maintain adequate ventilation, using relatively low minute ventilation. We speculate that such a maneuver, if applied during mechanical ventilation, may prevent secondary pulmonary damage by allowing the use of lower ventilator volume-pressure settings.

Variability in systemic arterial pressure during closed- and open-bridge extracorporeal life support: an in vitro evaluation.

OBJECTIVE: To compare fluctuations in systemic arterial pressure (SAP) resulting from changes in systemic vascular resistance (SVR) during closed- and open-bridge extracorporeal life support (ECLS). DESIGN: In vitro laboratory study. SETTING: Physiology laboratory of a tertiary care pediatric hospital. METHODS: A standard neonatal ECLS circuit with simulated SAP was established using normal saline as circulating fluid. Our reference setting included an extracorporeal flow rate of 300 mL/min, a simulated SAP of 60 mm Hg, and a postoxygenator pressure of 150 mm Hg. The simulated SVR was modified by changing the degree of occlusion of the arterial catheter distal to the bridge. For this purpose, we used a graduated clamping device. Subsequently, the pressure changes were measured at four ports in the circuit. They were located as follows: a) on the venous tubing of the circuit between the bridge and the reservoir; b) on the arterial tubing of the circuit between the heat exchanger and the bridge; c) between the first and the second resistance clamps on the arterial tubing of the circuit for monitoring the simulated systemic arterial pressure; and d) at the reservoir. The experiment was repeated with various extracorporeal flow rates to the reservoir (100-300 mL/min) and through the bridge (100-300 mL/min using a custom-made clamp). Variations in the simulated SAP created by varying degrees of occlusion and flow rates were compared with repeated measures analysis of variance followed by the Tukey-Kramer test. MEASUREMENTS AND MAIN RESULTS: The open-bridge ECLS significantly reduced the variations in the simulated SAP by 15% to 45% (p < .001) compared with the closed-bridge. During closed-bridge ECLS, flashing of the bridge resulted in a decrease in the SAP and transient reversal of flows through the arterial and venous cannulae. CONCLUSIONS: Open-bridge ECLS decreases the fluctuations in the SAP that occur because of changes in the SVR. Open-bridge ECLS prevents transient iatrogenic changes in blood flow and blood pressure, caused by flashing of the bridge. Other potential advantages and disadvantages of the open-bridge ECLS are discussed. The application of prolonged open-bridge ECLS to the patients needs to be evaluated in animal models.

Nitric oxide and nitrogen dioxide concentrations during in vitro high-frequency oscillatory ventilation.

PURPOSE: The purpose of this study was to measure nitric oxide (NO) and nitrogen dioxide (NO2) concentrations, at various ventilatory settings and sampling sites, during in vitro inhaled NO and high-frequency oscillatory ventilation therapy [iNO-HFOV]. MATERIALS AND METHODS: We used a high-frequency oscillatory ventilator (model 3100A, SensorMedics, Yorba Linda, CA), a test lung (model VT-2A Ventilator Tester, Bio-Tek Instruments, Inc., Winooski, VT), nitric oxide delivery and NO/NO2 monitoring (Pulmonox II, Pulmonox, Tofield, Canada), and scavenging systems in this study. The ventilator frequency, amplitude, and inspired oxygen concentration were systematically changed at a fixed flow of NO. The concentrations of NO and NO2, sampled at four sites, were determined by an electrochemical method (Pulmonox II). The NO and NO2 concentrations were measured at the proximal part of the inspiratory limb (site 1), near the Y-piece (site 2), the carina of the test lung (site 3), and the bellows of the test lung (site 4). RESULTS: The concentration of NO decreased significantly (P < .001) from the proximal port (site 11 of the inspiratory circuit (86.16 +/- 0.38 ppm) through the lung bellows (site 4) (70.08 +/- 0.23 ppm). The concentration of NO2 increased significantly (P < .001) from site 1 (3.25 +/- 0.04 ppm) through site 4 (19.4 +/- 0.19 ppm). However, the total concentration of NO + NO2 (NOx) remained unchanged at both site 1 and site 4. Increasing the frequency and amplitude of the ventilator significantly altered NO and NO2 concentrations. The NO2 concentration increased significantly (P < .0001) from 5.6 ppm to 18.1 ppm at site 4 when the fraction of inspired oxygen was increased from 0.25 to 0.93. The NO2 concentration also increased significantly (P < .0001) from 0.6 ppm to 18.7 when NO concentrations were independently increased from 12 ppm to 80 ppm. CONCLUSIONS: During HFOV, the concentrations of NO and NO2 vary between sampling sites and also are influenced by the frequency, amplitude, and inspired oxygen concentration. NO2 concentrations in the lung were significantly increased above commonly accepted toxic concentrations during ventilation with high concentrations of NO (80 ppm) and high fractional concentrations of oxygen. The excessive increase in NO2 concentration at the "alveolar" level in our test lung model warrants confirmation in an in vivo model.

Experimental critical care in rats: gender differences in anesthesia, ventilation, and gas exchange.

OBJECTIVE: To compare normative ventilatory and gas-exchange data and anesthetic requirements in male and female rats subjected to critical care conditions. DESIGN: Prospective study. SETTING: Critical care research laboratory in a hospital. SUBJECTS: Twenty-two age-matched young male and female rats (Sprague-Dawley, Long Evans strain). INTERVENTIONS: Anesthesia was induced with 65 and 45 mg/kg pentobarbital in male and female rats, respectively. The rats were then tracheostomized and cannulated in one femoral vein and artery. Anesthesia was maintained using 8-15 mg/kg/hr pentobarbital (iv) and controlled by continuous hemodynamic monitoring. MEASUREMENTS AND MAIN RESULTS: Normoxic baselines for breathing frequency, tidal volume, minute volume, inspiratory-to-expiratory ratio, inspiratory drive (tidal volume/inspiratory time), respiratory system compliance, peak airway pressure, and gas-exchange profiles were established. Ventilatory and gas-exchange responses to oxygen and CO2 were then determined by exposure to 10 mins of hyperoxia (100% oxygen), two levels of mild and severe hypercapnic hyperoxia (inspired Pco2 of 30 and 60 torr; 4 and 8 kPa), and two levels of mild and severe normocapnic hypoxia (inspired PO2 of 81 and 48 torr; 10.7 and 6.3 kPa). The average anesthetic requirement (during a 5- to 6-hr experiment) was 30% less in the female rats than in the male rats (p < .05). Female rats showed significantly lower breathing frequency, minute volume (mL/min/kg), and inspiratory drive (mL/kg/sec) during hyperoxia, mild and severe hypercapnia, and mild hypoxia. Pulmonary peak airway pressure was significantly lower in the female rats, consistent with a significantly higher weight-indexed compliance during all exposures. The female rats also had significantly higher inspiratory-to-expiratory ratio and higher PaCO2 with lower pH during normoxia, hyperoxia, and mild hypercapnia. These gender differences had no effect on PaO2, which was similar in all exposures. CONCLUSIONS: There are significant gender differences in ventilation, gas exchange, and anesthetic requirements in rats subjected to critical care conditions. The gas-exchange values observed in these spontaneously breathing rats may represent the optimal levels attainable during pentobarbital anesthesia with normal lungs. They may serve as standards for ventilator settings in the rat models used for critical care studies.

Fewer interventions in the immediate post-extubation management of pediatric intensive care unit patients: safety and cost containment.

PURPOSE: The purpose of this article was to compare the safety and patient charges of two postextubation treatment regimens. MATERIALS AND METHODS: Twenty-two pediatric patients, between the ages of 7 months and 13 years, who were mechanically ventilated for less than 5 days were studied in a prospective randomized nonblinded study at a multidisciplinary pediatric intensive care unit. Immediately after extubation all patients received supplemental oxygen, administered via mask or nasal cannulae, at a flow rate or concentration sufficient to maintain the pulse oximetric arterial oxygen saturations > 95%; arterial blood gas analyses were performed at 30 minutes after extubation. The subjects were randomly assigned to one of two protocols. Protocol A (our standard management) consisted of (1) three nebulized albuterol treatments administered 1 hour apart, and (2) a chest radiograph obtained within 60 minutes of extubation. Protocol B included one nebulized albuterol treatment administered immediately after extubation. We measured the heart rate, respiratory rate, and arterial blood pressure immediately after and at 60, 120, and 180 minutes following extubation. The following data were also recorded: arterial blood gas analysis results and continuous pulse oximetric arterial oxygen saturation levels. Any significant complications, such as stridor, respiratory distress, or requirement for reintubation, were noted if they occurred within 24 hours of extubation. Patient charge costs were calculated after obtaining the prevailing hospital and physician charges at the time of the study. RESULTS: Eleven patients completed each arm of the study (total = 22). There were no statistically significant differences between the two groups with respect to arterial pH, serum bicarbonate, pulse oximetric arterial oxygen saturation, arterial blood pressure, respiratory rate, or heart rate (P > .05). Patients treated with Protocol A had a statistically, but not clinically, significant higher mean PaO2 and PaCO2 (P = .02 and P = .05, respectively) than those in Protocol B. Associated charges per patient for Protocol A were $863.50 versus $476.00 for Protocol B. This is a savings of $387.50 per patient. Our pediatric intensive care unit provides care to over 600 intubated patients per year, which would equate to a charge savings of $232,500.00 per year. CONCLUSION: A modified postextubation management protocol, consisting of fewer interventions, resulted in significant patient charge savings with no increased risk to the patient.

[Intraosseous puncture as vascular access in pediatric emergency and intensive care medicine]. / Die intraossäre Punktion als Gefässzugang in der pädiatrischen Notfall- und Intensivmedizin.

In paediatric resuscitation scenarios, emergency physicians have sufficient skills in endotracheal intubation. They are successful in about 80% of the cases as US studies indicate. However, vascular access is much more of a critical problem and emergency physicians succeed in only 50%. Therefore, intraosseous access has become an internationally widely used and accepted method for venous access. In Germany, however, only case reports concerning this technique have been published. Based on the authors' experience shared with Sussmane and Raszynski in the US, we used the technique of intraosseous access in 18 paediatric resuscitative situations. Eleven patients survived who would not have done so without quick intravenous access. As complications we recorded a minor fracture, one compartment syndrome, which did not require surgical intervention, and a postmortally discovered minor fat embolism, which was of no clinical significance. Courses teaching this method should be offered in Germany to spread knowledge of this life-saving technique.

Cerebral tissue oxygenation during hypoxia and hyperoxia using artificial placentation in lamb.

Aiming at a better understanding of the pathophysiologic basis of perinatal encephalopathy, we evaluated patterns of tissue oxygenation during hypoxia and hyperoxia. We utilized both laserspectroscopy and invasive tissue-Po2 microneed measurements synchronously in five newborn lambs (141-143 days of gestation). The model of artificial placentation provided defined changes of the blood gases, using a extracorporeal circuit with interposition of membrane lung. During hyperoxia, the Po2 at the blood outlet port of the lung was raised to > 300 mmHg for five minutes. During hypoxia, Po2 was diminished as oxygen at the gas phasis was replaced by nitrogen. After the induction of hyperoxia, a rise of tissue-Po2 was observed. The synchronously recorded data of the laserspectroscopy showed adequately rising HbO2 values in concordance (r = 0.97, p < 0.001). As a constant finding we did not observe Cyt-aa3 changes during induced hyperoxia with tissue-Po2 values of < 40 mmHg. Furthermore, no changes in blood volume occurred in this case. A different pattern of the laserspectroscopic parameters was found when the tissue-Po2 rose above a value of > 40 mmHg and Cyt-aa3 rose after a lag-time occurred. During induced hypoxia an immediate fall of tissue-Po2 corresponding with a fall of HbO2 in the spectroscopic tracing occurred (r = 0.87, p < 0.001). A fall of the Cyt-aa3 level was seen with a lag-time when the tissue-Po2 had reached values of below 10 mmHg. In addition, a rise of blood volume was recorded in all cases of induced hypoxia. In conclusion, the results indicated that cellular redoxe state remains stable over a large range of oxygen partial pressure changes.

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.

Changes in plasma levels of oxygen radical scavenging enzymes during extracorporeal membrane oxygenation in a lamb model.

We studied levels of superoxide dismutase, glutathione, reductase, glutathione peroxidase and lipoperoxides in 12 healthy lambs below 1 year of age (8-19 kg) under therapy with extracorporeal membrane oxygenation (ECMO). Plasma levels of these free oxygen radical scavenging enzymes and lipoperoxides were taken 1 day before the ECMO experiment, at the beginning of ECMO after the first rotations of the roller pump, during, and after ECMO. The pre-ECMO results of days 1 and 2 were compared with the during-ECMO results and those with the post-ECMO results using the t test for paired samples. We found a significant decrease of both superoxide dismutase and glutathione reductase on ECMO, a trend to increased lipoperoxide levels, and unchanged levels of glutathione peroxidase. After discontinuing bypass the levels began to normalize again. We conclude that ECMO reduces some oxygen radical scavenging enzyme levels and exhibits a trend to increased lipoperoxide levels. Near total lung collapse with consecutive reperfusion injury might be harmful considering these results. However, the nonsignificant increase in lipoperoxide levels excludes considerable oxygen toxicity during this short ECMO trial.

Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep.

BACKGROUND AND METHODS: Critically ill infants undergoing extracorporeal membrane oxygenation (ECMO) therapy often receive multiple pharmacologic agents. Although the disposition of many drugs has been assessed in patients undergoing cardiopulmonary bypass and in patients receiving mechanical ventilation, only limited data exist for selected medications in patients undergoing ECMO. To evaluate the potential influence of ECMO on aminoglycoside pharmacokinetics, we studied the disposition of tobramycin in ten sheep before and during ECMO therapy. Each sheep received a single iv dose of tobramycin during a control period before ECMO and on a study day during ECMO. Identically timed serial blood samples over 4 hrs were obtained after each tobramycin dose. Paired serum tobramycin concentrations were obtained pre- and postmembrane oxygenator during ECMO in six sheep. RESULTS: Alterations in specific pharmacokinetic variables for tobramycin were observed as a result of ECMO. Estimates of elimination half-life and volume of distribution for tobramycin were significantly increased during ECMO as compared with control (pre-ECMO) values (1.8 +/- 0.3 vs. 2.7 +/- 0.8 [SD] hrs [p < .01] and 0.3 +/- 0.1 vs. 0.5 +/- 0.2 L/kg [p < .005], respectively). Tobramycin body clearance was unaffected by the procedure (1.8 +/- 0.8 vs. 1.7 +/- 0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and postmembrane oxygenator demonstrated no drug removal. CONCLUSIONS: These data suggest that ECMO circuitry does not sequester tobramycin and that the prolonged elimination half-life observed during ECMO therapy is not due to a change in drug clearance but is due to an ECMO-induced increase in tobramycin volume of distribution. To achieve and maintain preselected target tobramycin serum concentrations during ECMO, the usual dosage interval should remain unchanged, but the dose should be increased to compensate for the alteration in the drug's volume of distribution. The clinical applicability of these findings needs to be confirmed in carefully controlled clinical studies involving infants receiving ECMO therapy.

[The treatment of severe pulmonary hypertension in newborn infants using extracorporeal membrane oxygenation or conventional measures. An interinstitutional comparison]. / Behandlung der schweren pulmonalen Hypertension des Neugeborenen mittels extrakorporaler Membranoxygenierung oder konventioneller Massnahmen. Ein interinstitutioneller Vergleich.

In a two years retrospective study we analyzed neonates from a US and a German neonatal center with pulmonary hypertension (persistent fetal circulation--PFC). The US patients were treated with Extracorporeal Membrane Oxygenation (ECMO) the german patients with conventional methods as hyperventilation, catecholamines, and vasodilators. Both groups fulfilled the classical ECMO entrance criteria: an alveolar-arterial oxygen difference greater than 610 mmHg and an oxygenation index (i.e. mean airway pressure x FiO2 x 100/paO2 of greater than 40 mmHg. We compared anamnestic and respiratory parameters with the t-test for independent groups or the chi-square test accordingly. With one patient in each group the mortality was not significantly different and the rate of meconium aspirations was the same. The APGAR score at 5 min was significantly lower in the US group, prenatal care was undertaken in significantly less US than german patients. Time intervals between delivery and important therapeutic interventions as intubation, hyperventilation, first catecholamines were not significantly different between both groups. Also worst paO2, pH, and paCO2 were not significantly different. Mechanical ventilation was more aggressive in the US group, i.e. higher intermittent-mandatory-ventilation-rate and peak inspiratory pressure. On the one hand our studies demonstrate that even patients fulfilling ECMO criteria still have a good chance with conventional treatment. On the other hand differences in APGAR scores and prenatal care might indicate that hypoxic-ischemic influences alter the US-group morbidity.

Thrombotic lesions of the tricuspid valve in the newborn.

Two cases of nonbacterial endocardial thrombi (NBET) on the atrial surface of the tricuspid valve in the full-term infant are presented. The pathophysiology and the events peculiar to the full-term infant that suggest susceptibility to this rare pathological phenomenon are reviewed. The difficulties in diagnosis and treatment are discussed.