Search

To investigate clinical and demographic factors affecting the nature of end-of-life decisions and pediatric palliative care.Charts of 236 expired children were retrospectively reviewed for presence of endof- life care (EOLC) discussions and spiritual support, the nature of EOLC decisions, and the degree of opioid analgesics (OA) and sedatives (SDT) administration.Approximately 60% of patients had EOLC discussion, of whom 87.4% obtained an EOLC decision, mostly opting for withholding therapy (68.8%). Presence of EOLC discussion was associated with a longer hospital stay (univariate analyses: odds ratio [OR] = 1.9; p0.029), higher number of failed organs (OR = 2.5; p0.003), chronic illnesses (OR = 2.4; p0.002), spiritual support (OR = 1.8; p0.028) and respiratory diseases (OR = 3.1; p0.0006). Younger patients and those with higher number of failed organs were more likely to have withdrawal of therapy (OR = 10.9 and 6.0; p0.0001 and0.002, respectively), whereas patients with chronic illness opted for withholding of therapy (OR = 3.1; p0.006). Spiritual support was associated with higher use of both OA and SDT (OR = 1.9 and 2.3; p0.014 and p0.005, respectively). Younger patients received less OA and SDT (OR = 0.2 and 0.4, respectively; p0.0001). Multivariate analyses showed that EOLC discussion is associated with higher use of OA and SDT (OR = 4.4 and 4.2; p0.00001 and p0.0001, respectively), whereas younger age is associated with withdrawal of therapy (OR = 8.3; p0.0005) and lower use of SDT (OR = 0.23; p0.0001).Patterns of care at the end of life vary in children with differing clinical and demographic characteristics. Because EOLC discussions are associated with greater focus on palliative care, strategies to enhance EOLC communications for pediatric patients should be further evaluated.

The criteria for starting extracorporeal membrane oxygenation (ECMO) therapy in term newborn patients with hypoxemic respiratory failure consist of an oxygenation index (OI) of 25 or higher and alveolar-arterial oxygen (Aao(2)) gradient of more than 600 at sea level. In such conditions, inhaled nitric oxide (iNO) may improve oxygenation and reduce the need for ECMO therapy. We studied early changes in OI and Aao(2) gradients in response to iNO treatment that may indicate a need to continue iNO treatment or the necessity to start an ECMO therapy.In this prospective study, we used 34 outborn neonatal patients that were referred to our pediatric critical care unit in a children's hospital for ECMO therapy with diagnosis of hypoxemic respiratory failure. In all patients, iNO therapy, starting at 80 ppm, was instituted either during transport or on arrival to hospital. Response to iNO was assessed after 1 hour, at which time, iNO concentration was reduced to 40 ppm, provided there was more than 20% improvement in either or both oxygenation indices. Patients who did not respond positively to continuous iNO therapy and met ECMO criteria were given ECMO therapy.Inhaled nitric oxide therapy alone was successful in 10 (29%) of 34 patients. Eighteen patients (53%) required ECMO therapy within the first 10 hours of iNO treatment (early ECMO therapy), whereas 6 other neonates (18%) became eligible for ECMO therapy after prolonged (2-4 days) iNO treatment (late ECMO therapy). No mortality occurred with any treatment. Within 4 hours after iNO therapy, patients who required early ECMO therapy had significantly higher OI and Aao(2) gradients than patients who were treated with iNO therapy alone (P.01, analysis of variance followed by Tukey-Kramer multiple comparison test). Six of 34 patients (18%), categorized as late ECMO therapy, on the average, had initially higher levels of OI and mean airway pressure than neonates in iNO treatment and early ECMO therapy.Persisting levels of OI of more than 20 or Aao(2) gradients of more than 600 after 4 hours of iNO therapy could be indicative of an immediate need for ECMO therapy.

Phosphodiesterase inhibitors, such as pentoxifylline and aminophylline, may reduce inflammatory cytokine-induced endothelial permeability. We tested the hypothesis that aminophylline treatment may ameliorate the pulmonary and extrapulmonary effects of endotoxemia in a rat model. In anesthetized rats, a tracheotomy was performed along with catheterization of a femoral vein and artery. Anesthesia, fluid balance, and normothermia were maintained throughout the 6-h experiment. A stable hemodynamic and gas-exchange baseline was established at which time the rats were randomly divided into three groups. Group I received aminophylline (1mg/kg) over 30 min followed by 0.5mg/kg/h. Group II received a single dose of endotoxin (4 mg/kg) while Group III received both aminophylline and endotoxin as described for Groups I and II, respectively. Gas-exchange profiles, mean arterial blood pressure, and heart rate were determined every 2h. At hour 6, the rats were euthanized and lung, kidney, and heart tissue were removed for determination of water content. As our control group, we utilized data from our previously published study involving an identical surgical procedure with normal saline. Endotoxemia produced characteristic respiratory and hemodynamic signs of sepsis including hypotension, hyperventilation, tachycardia, and renal and pulmonary edema. Aminophylline treatment failed to prevent these endotoxemia-induced respiratory and hemodynamic manifestations of sepsis, but significantly improved the acid-base imbalance that developed during surgical procedures in saline-treated control rats. Further studies are warranted to determine potentially beneficial doses of aminophylline and resulting theophylline serum concentrations under such septic conditions.

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 ± so). Interventions: The lambs initially were anesthetized by 50 mglkg ketamine intravenously. After tracheostomy, the lambs were mechanically ventilated and paralyzed by using 1 mglkg 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°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 Paco 2 (25-35 mm Hg) at an Flo 2 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. CO 2 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 Flo 2 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 Flo. 2 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.

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

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.

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 °C (normothermia), and during stepwise hypothermia at 37, 35, 33, 31 and 29 °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 °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 °C). The PaO2, however, was significantly reduced below 31 °C. The MAP remained stable at different levels of hypothermia, whereas HR was significantly reduced below 33 °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.

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 1) 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.

Introduction Clinical application of arteriovenous (AV) extracorporeal membrane oxygenation (ECMO) requires assessment of cardiovascular ability to respond adequately to the presence of an AV shunt in the face of acute lung injury (ALI). This ability may be age dependent and vary with the experimental model. We studied cardiovascular stability in a lamb model of severe ALI, comparing conventional mechanical ventilation (CMV) with AV-ECMO therapy. Methods Seventeen lambs were anesthetized, tracheotomized, paralyzed, and ventilated to maintain normocapnia. Femoral and jugular veins, and femoral and carotid arteries were instrumented for the AV-ECMO circuit, systemic and pulmonary artery blood pressure monitoring, gas exchange, and cardiac output determination (thermodilution technique). A severe ALI (arterial oxygen tension/inspired fractional oxygen 0.05; Fisher's exact test). Surviving and nonsurviving lambs in the AV-ECMO group, unlike the CMV group, required continuous volume expansion and inotropic support (P < 0.001; Fisher's exact test). Lambs in the AV-ECMO group were able to maintain normocapnia with a maximum of 30% reduction in the minute ventilation, as compared with the CMV group (P < 0.05). Conclusion AV-ECMO therapy in lambs subjected to severe ALI requires continuous hemodynamic support to maintain cardiovascular stability and normocapnia, as compared with lambs receiving CMV support.

Objectives: We tested the hypothesis that an increase in the blood colloid osmotic pressure (COP) that is maintained during early-stage endotoxemia may decrease fluid flux across capillaries and may reduce pulmonary and multiple-organ edema. Design: Prospective study. Settings: Research laboratory in a hospital. Subjects: Male albino Sprague-Dawley rats. Interventions: Rats were anesthetized with pentobarbital, underwent tracheotomies, were cannulated in the femoral vein and artery, and were randomly assigned to the following four groups comprising 11 rats each: group I, controls (saline solution treatment); group II, albumin treatment (three doses of 1 g/kg 25% human albumin every 2 h); group III, endotoxin treatment with a single IV dose of 4 mg/kg endotoxin; and group IV, endotoxin and albumin-treatment (4 mg/kg endotoxin plus albumin treatment). Experiments lasted for 6 h while fluid intake was equally maintained in all groups. Measurements and results: COP and other variables were measured every 2 h. To determine the water content of an organ, after the rat was killed, the lung, heart, kidney, intestine, and liver were removed. Albumin treatment alone (group II) generated significant increases in COP (maximum, 58% from the baseline measurement) but did not change the water content of the organ, compared with saline solution-treated controls. Endotoxin-treated rats (group III) developed significant reductions in COP, with significant increases in pulmonary, renal, and heart water content compared with controls. Albumin treatment in endotoxemic rats (group IV) significantly increased the COP without improving the endotoxemia-induced organ edema. Pulmonary edema, however, was increased further, compared with endotoxemia alone. Conclusions: COP elevation by albumin administration during the early stage of endotoxemia does not ameliorate pulmonary or multiple-organ edema and may aggravate pulmonary edema. (CHEST 2001; 120:1655–1662)

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.

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

Purpose: We have previously demonstrated an increased arterial o2-carrying capacity in normal ventilated dogs subjected to both acute and prolonged exogenous hypercapnia. In the present study, we tested if arterial hypercapnia, during controlled ventilation, can increase 02-carrying capacity also in rats. Materials and Methods: Twenty young male Sprague Dawley rats were anesthetized (60 mg/kg pentobarbital), tracheostomized, intubated, and one femoral vein and artery were cannulated. Anesthesia and paralysis were maintained using 15 mg/kg/h pentobarbital intravenously, and 2 mg/kg/h vecuronium bromide. The fluid balance (5 mL/kg/h saline), normothermia, and minute volume were maintained. The mean arterial blood pressure and heart rate were continuously monitored. Experiments included the following: (1) a control group, ventilated with normoxic air for 150 minutes (n = 5); (2) mild hypercapnia, a group of eight rats ventilated with normoxic air for 30 minutes and then ventilated with a mixture of normoxic air at 60 mm Hg C02 (8 kPa) for 1 hour; and (3) severe hypercapnia, a group of seven rats were treated exactly as in group II, except a 90 mm Hg (12 kPa) C02 during hypercapnia. Gas-exchange profile, arterial hemoglobin (Hb) concentration, arterial Hb-oxygen saturation (Hb-O2), and arterial O2 content were periodically determined during normocapnia and 1 hour of hypercapnia. Results: Exposures to mild and severe hypercapnia, in rats with maintained ventilation, significantly reduced the arterial O2 content by 20% and 33%, respectively, without significant changes in the arterial Hb concentration (−2%). Severe hypercapnia generated a significant reduction of −14% in the PaO2, but not in PaO2/Fi02 ratio. Conclusion: Rats subjected to controlled ventilation and permissive hypercapnia, unlike dogs and perhaps humans, show no augmentation of Hb concentration. Hypercapnia in rats also provokes much stronger Bohr effect than in dogs. Hypercapnia-induced Bohr effect in rats is accompanied with extreme desaturations of Hb-O2, and substantial reduction in the 02-carrying capacity. We speculate that the strong hypercapnia-induced Bohr effect in rats may prevent hypoxia at the tissue level. However, to maintain a stable oxygen-carrying capacity in rats used for pulmonary critical care studies with hypercapnia, we suggest to use hyperoxia, with or without a mild hypothermia.

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 CO 2 were then determined by exposure to 10 mins of hyperoxia (100% oxygen), two levels of mild and severe hypercapnic hyperoxia (inspired Pco 2 of 30 and 60 torr; 4 and 8 kPa), and two levels of mild and severe normocapnic hypoxia (inspired Po 2 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

OBJECTIVE: To present a case of the use of alteplase for the successful resolution of an upper extremity occlusion in a newborn receiving extracorporeal membrane oxygenation (ECMO). CASE SUMMARY: A two-day-old full-term Hispanic girl receiving ECMO support developed a left upper extremity occlusion distal to the brachial artery. Alteplase therapy was initiated with a bolus dose of 0.48 mg/kg followed by a continuous infusion of 0.27 mg/kg/h for three hours. A repeat Doppler ultrasound revealed little improvement, resulting in continuation of alteplase therapy at an infusion rate of 0.27 mg/kg/h for an additional three hours. At the completion of the infusion, perfusion was greatly improved with palpable radial pulse present. While remaining on ECMO support, a brain ultrasound approximately 13 hours after alteplase therapy revealed a grade I right caudate head hemorrhage with normal ventricles. ECMO support was discontinued during the next 24 hours, with a repeat brain ultrasound three days later indicating no acute hemorrhage, normal ventricles, and almost complete resolution of the intraventricular hemorrhage. The neonate was discharged 19 days after discontinuing ECMO support. DISCUSSION: Patients receiving ECMO support are at risk of hematologic complications, including thrombi formation. Moreover, limited information is available regarding the most appropriate thrombolytic therapy for patients receiving ECMO support. Alteplase is an attractive thrombolytic agent given its antigenicity, clot specificity, and pharmacokinetic profile. However, both ECMO support and thrombolytic therapy are risk factors for the development of intraventricular hemorrhage, which our patient developed. Therefore, close monitoring of patients receiving ECMO support and alteplase therapy is essential given the potential for hematologic adverse effects. CONCLUSIONS: Alteplase is an effective thrombolytic agent in neonates receiving ECMO support. Additional experience with alteplase is necessary to determine the optimal dose and duration of therapy in this patient population.

To test the hypothesis that PaCO2 levels generated during permissive hypercapnia may enhance arterial oxygenation, when ventilation is maintained.Prospective study.Research laboratory in a hospital.One group of eight mongrel dogs (four male; four female).The dogs were anesthetized (30 mg/kg iv pentobarbital), intubated, and cannulated in one femoral artery and vein. While paralyzed with 0.1 mg/kg/hr iv vecouronium bromide, all subjects were ventilated with room air. Anesthesia was maintained, using 2 to 3 mg/kg/hr iv pentobarbital. Arterial hypercapnia at the levels generated during permissive hypercapnia was produced by stepwise increases in the dry, inspired Pco2 (PiCO2) (0, 30, 45, 60 and 75 torr [0, 4, 6, 8, and 10 kPa]; 15 mins each).Blood gas profiles were determined at each level of hypercapnia. The minute volume was maintained at the baseline level during all exposures. Arterial hypercapnia produced gradual and significant increases in the hemoglobin concentration. These increases were approximately 6%, 7%, 11%, and 14% at PiCO2 of 30, 45, 60, and 75 torr (4, 6, 8, and 10 kPa), respectively (p.05; repeated analysis of variance followed by Dunnett multiple comparisons test). In parallel, the oxygen content increased by approximately 6%, 7%, 11%, and 13%, respectively. During hypercapnic trials, the PaO2 remained at the normal range, whereas the dry, inspired PO2 (PiO2) was reduced from 150 to 138 torr (20 to 18.4 kPa). The average PaO2 at the highest investigated level of arterial hypercapnia was at a normal range. The hemoglobin concentration and oxygen content returned to baseline values 30 mins after hypercapnic trials. The PaCO2 and pH became normalized 15 mins after hypercapnic trials. Indirect evidence for a similar response to hypercapnia in humans is presented.Permissive hypercapnia due to inhaled CO2 increases oxygen-carrying capacity in dogs. The PaO2 remains at normal range even at a PiCO2 of 75 torr (10 kPa). The benefits of these effects during permissive hypercapnia, due to controlled hypoventilation, warrants investigation.

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 Pa O 2 and Pa CO 2 (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.

378 Brain Differential Gene Expression in Neonatal Rats: Age- and Gender-Related Differences

Background Splanchnic perfusion following hypovolemic shock is an important marker of adequate resuscitation. We tested whether the gap between esophageal partial carbon dioxide tension (PeCO2) and arterial partial carbon dioxide tension (PaCO2) is increased during graded hemorrhagic hypotension and reversed after blood reinfusion, using a fiberoptic carbon dioxide sensor.

Introduction: Accurate measurement of airway pressures (Paw) are crucial during mechanical ventilation. Intratracheal pulmonary ventilation(ITPV) utilizes a reverse thruster device to deliver a continuous flow of gas at the level of the carina, thereby generating a different carinal Paw than conventional ventilation (CV). This study compares the proximal and carinal Paw during CV and ITPV, in both an artificial lung an in a rabbit model.

Introduction: The standard ECMO circuit has a bridge between the venous drainage and infusion tubing. This allows temporary dissociation of the patient from the ECLS circuit. Traditionally, while weaning from ECMO, pump and patient flows are not reduced below 100 ml/min for newborn and kept much higher in older children to prevent clotting in the circuit and the membrane oxygenator. These low flows during weaning may represent more than a third of the patient's cardiac output. Trialing off of the patients from ECMO at these flows may fail. We have used an open-bridge technique to maintain high pump flows through the circuit and were able to reduce the patient flows to much lower rates and achieved a more stable and successful rate of decannulation. We are reporting the successful clinical application of partially opened bridge ECMO for weaning.

Introduction: Extracorporeal life support (ECLS) is used for the support of cardiorespiratory failure. The standard ECLS circuit has a bridge between venous drainage and infusion tubing. This allows temporary dissociation of the patient from the ECLS circuit. The bridge is opened intermittently to prevent clotting (called flashing). Changes in systemic arterial pressure (SAP) due to changes in systemic vascular resistance (SVR) have been reported during flashing of the bridge which can be avoided if the bridge is kept partially open. An in vitro method is developed to study variations in SAP during closed and open-bridge ECLS.

SUMMARY 1. Metoclopramide hydrochloride (Maxolon) a potent intestinal clearing agent and powerful anti-emetic, was utilized to promote gastric clearance of kerosene from baboons, experimentally poisoned. 2. When compared to a control group, treated baboons have significantly decreased amounts of kerosene in the stomach 2 h after treatment, ‘full’ stomach/body weight ratios confirming this. 3. The study suggests that metoclopramide, by its gastric clearing and anti-emetic action, may reduce the risk of vomiting, and thus of aspiration pneumonia, in kerosene poisoning.

Eighty to 100 per cent oxygen, breathed by lambs one or two weeks of age, is lethal after two to four days. Artificial ventilation did not aggravate or significantly ameliorate the pulmonary response. Lambs ventilated with air on respirators for comparable periods had no significant pulmonary damage. The cause of death of the oxygen-treated lambs was the pulmonary injury, characterized by edema. Studies of the excised lungs showed that the lesion was spotty, that the normal-appearing portions of the lung were normally distensible, and no significant alterations in pulmonary surfactant occurred. Several methods of assessment of the mechanical derangements are presented.

Aerosol deposition in the upper and lower respiratory tract using technetium-labelled water aerosol, produced by jet and ultrasonic nebulizers, with and without 10% propylene glycol, was examined under conditions of nasal, normal mouth, and tube breathing in 15 normal adults. With nasal breathing, 91.5% (± 5.5) and 83.2% (± 6.3) of the mass of the aerosol produced by the jet and ultrasonic nebulizers, respectively, was deposited in the upper respiratory tract. Similar fractional depositions were observed with the addition of 10% propylene glycol. When breathing was carried out via a mouth tube, 43% to 59% of the mass of the aerosol produced by the nebulizers was deposited in the upper respiratory tract. The mass median diameters of the available aerosols produced by the jet and ultrasonic nebulizers were 6.0 µ (geometric standard deviation = 2.5) and 2.8 µ (geometric standard deviation = 2.1), respectively; the densities of the aerosols produced were 8 and 34 µl/liter air. With nasal or normal mouth breathing, the volume of water, in aerosol form, that could be deposited per 24 hours in the lower respiratory tract of an adult was calculated to be about 6 ml and 49 ml for the jet and ultrasonic nebulizer, respectively.

The management of the infant of a tuberculous mother requires individualization with respect to consideration of the state of maternal disease, likelihood of congenital infection, and subsequent risk to the infant. If the mother has active disease and is sputum positive, BCG and separation of the infant until he becomes tuberculin positive, or the mother becomes sputum negative are recommended. If the mother is sputum negative, and known to be taking medication regularly, on if the mother has a history of tuberculosis adequately treated, she should have a chest film at delivery and 3 and 6 months thereafter, and the infant should be tuberculin tested every 3 months. The use of BCG in such an infant is optional, but it should be considered if careful followup of the infant is uncertain.

Children with dwarfism can be screened for deficiency of growth hormone by means of radioimmunoassay. In patients who are able to secrete the hormone two samples taken at 31/2 and 4 hours after a glucose load of 1.4 g. per kg. provide a safe and simple method of detecting human growth hormone. Only those patients who show no growth hormone in this screening test need be tested more rigorously. Other and more thorough procedures can then be used to confirm the deficiency.

Baboons were utilized to investigate the clinicopathologic effects of kerosene, given via various routes, on the primate brain. The animals were divided into five groups: Group 1 - normal controls; Group II - kerosene administered intratracheally; Group III - kersoene injected into the left cardiac ventricle; Group IV - kerosene injected into right carotid artery; Group V - kerosene injected into portal vein. Results indicate that the primate brain is resistent to the direct toxic effects of kerosene. Even when the dose is very large, the microcirculation of the liver and lung filter out sufficient amounts of kerosene to protect the brain from damage. It is assumed that the CNS manifestations following ingestion of kerosene are due to hypoxia secondary to aspiration pneumonia.

The accuracy of a 6-hr vs a 24-hr urine collection for the determination of urinary urea nitrogen was studied in 15 infants. Patient's age ranged from 2 weeks to 3 yr, encompassing a wide variety of diagnoses. All patients had normal renal function at the time of the study.Participants had indwelling foley catheters throughout the study. Urine specimens were collected over a continuous 24-hr period. Aliquots obtained from urine collected over 0 to 6 hr and the total urine collection were analyzed utilizing the urease enzymatic method in the Astra.Statistical analysis was performed comparing the actual 24-hr determination to the estimation based on the 6-hr collection, utilizing linear regression. The analysis of data produced a highly significant correlation (r = 0.904, p < 0.0001).When a 24-hr urine collection is not possible, a 6-hr collection is a useful alternative for the calculation of nitrogen balance in infants. (Journal of Parenteral and Enteral Nutrition10:517-518, 1986)