Jeffrey B. Sussmane

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.

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 °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.

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

ObjectiveTo 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. DesignProspective study. SettingResearch laboratory in a hospital. SubjectsSeven lambs (5.5 ± 0.6 kg, mean ± sd). InterventionsThe 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°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%. ConclusionsHealthy 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.

Effect of extracorporeal membrane oxygenation on tobramycin pharmacokinetics in sheep.

Background and MethodsCritically 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. ResultsAlterations in specific pharmocokinetic variables for tobramycin were observed as a result of ECMO. Estimates of elimination halflife and volume of distribution for tobramycin were significantly increased during ECMO as compared with control (pre-ECMO) values (1.8 ±PT 0.3 vs. 2.7 ±PT 0.8 [SD] hrs [p < .01] and 0.3 ±PT 0.1 vs. 0.5 ±PT 0.2 L/kg [p < .005], respectively). Tobramycin body clearance was unaffected by the procedure (1.8 ±PT 0.8 vs. 1.7 ±PT 0.4 mL/min/kg). Paired serum tobramycin concentrations obtained pre- and postmembrane oxygenator demonstrated no drug removal. ConclusionsThese 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 drugs volume of distribution. The clinical applicability of these findings needs to be confirmed in carefully controlled clinical studies involving infants receiving ECMO therapy.

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.

Cardiovascular stability during arteriovenous extracorporeal therapy: a randomized controlled study in lambs with acute lung injury

IntroductionClinical 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.MethodsSeventeen 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 <200) was induced by lung lavage (repeated three times, each with 5 ml/kg saline) followed by tracheal instillation of 2.5 ml/kg of 0.1 N HCl. Lambs were consecutively assigned to CMV treatment (n = 8) or CMV plus AV-ECMO therapy using up to 15% of the cardiac output for the AV shunt flow during a 6-hour study period (n = 9). The outcome measures were the degree of inotropic and ventilator support needed to maintain hemodynamic stability and normocapnia, respectively.ResultsFive of the nine lambs subjected to AV-ECMO therapy (56%) died before completion of the 6-hour study period, as compared with two out of eight lambs (25%) in the CMV group (P > 0.05; Fishers 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; Fishers 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).ConclusionAV-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.

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°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.

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

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

863.50 versus

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

476.00 for Protocol B. This is a savings of