Continuous octreotide infusion for treatment of upper gastrointestinal bleeding due to portal hypertension in children: An observational study from pediatric intensive care unit.

Evaluate the usage of octreotide for the control of acute upper gastrointestinal bleeding in children with portal hypertension. A retrospective electronic database analysis of these children was performed over a period of five years. Setting was a tertiary pediatric intensive care. Case notes of 18 encounters in 13 children were reviewed. A loading dose (1.27 ± 0.76 µg/kg) was administered in seven, with median starting dose of 1.44 ± 1.19 µg/kg/h in all other episodes. The mean maximum dose was 1.68 ± 1.38 µg/kg/h. Re-bleeding occurred in one third; hemostasis was eventually achieved in all. Octreotide infusion appears to be safe and effective in controlling pediatric upper gastrointestinal bleeding due to portal hypertension. We also recommend its use in community and rural hospital settings prior to transfer of such patients to a tertiary care center.

Age and sex differences in brain gene expression in neonatal rats.

Gene expression in the central nervous system is highly region-specific. We tested the hypothesis that certain developmental biomarkers could be detected in the whole brain or in cortical, subcortical or cerebellar structures. Brain gene expressions of male and female rats at birth, 3 days, and 10 days of age were measured by microarray technique ( approximately 10 K genes; n=9/category). We found 53 significantly up-regulated and 8 down-regulated genes at 10 days of age, relative to birth and 3 days of age. The whole brain, however, showed no significant sex differences in gene expression patterns up to 10 days of age. Ten genes with the highest up-regulation, and 5 down-regulated genes were further confirmed by quantitative real-time PCR (Q-PCR), using the whole brain, cortices, subcortical structures, and cerebellum. The Q-PCR confirmed genes are known to be involved in neuronal differentiation, axonal myelination and growth, neurotransmission and glycolytic pathways. With a few exceptions, the expression levels of Q-PCR confirmed genes were significantly different in the whole brain, compared to other regions. In a separate study, we tested the potential utility of the Q-PCR confirmed genes, as whole brain biomarkers, after a six-hour exposure to hyperoxia (>98% oxygen breathing) in 10 days old rats. This relatively mild oxidative challenge created a 3.5-fold increase in the expression of T-cell receptor beta Variable 8.3b, known to have regulatory function during development. We suggest that genes displaying significant expression in the whole brain, regardless of their origin, could be used to screen normal brain development in neonatal rat models of experimental neurology.

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.

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.

Intratracheal pulmonary ventilation in a rabbit lung injury model: continuous airway pressure monitoring and gas exchange efficacy.

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.

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.

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.

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.

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 significance of the initial respiratory parameters in assessing the severity of ARDS in children]. / Die Bedeutung initialer respiratorischer Parameter zur Schweregradbeurteilung beim ARDS im Kindesalter.

In adults, the course and outcome of the acquired respiratory distress syndrome (ARDS) are closely related to the initial respiratory situation. Respiratory indices are frequently used for prognostic purposes and hence for the institution of new techniques such as extracorporeal lung support. The validity of these indices to predict the outcome in pediatric ARDS patients has not been examined as yet. We studied respiratory indices in 69 pediatric ARDS patients. METHODS. Out of 69 pediatric ARDS patients with various underlying diseases (Table 1), we chose 21 with a paO2/FiO2 ratio less than 150 mm Hg at some point to test the prognostic significance of a respiratory severity index (RSI), i.e., mean airway pressure x alveolar-arterial pO2 difference (A-aDo2)/paO2, a respiratory index (RI), i.e., A-aDO2-paO2/paO2, and other respiratory parameters (Table 2). Postsurgical patients, patients with incurable diseases, clearly non-respiratory deaths, and those treated with extracorporeal membrane oxygenation were excluded. We looked for statistical differences between survivors and nonsurvivors and correlations between ventilator days, intensive care unit (ICU) days, and hospital days and these indices. RESULTS. We did not find a significant difference between all respiratory indices tested at admission to the ICU and 24 h later between survivors and nonsurvivors (Table 3). Nonsurvivors initially had significantly higher blood pressures and lower heart rates. Both RSI and RI were significantly correlated to days on the ventilator, days in the ICU, and days in the hospital (Table 4). Initial multiorgan failure was significantly more common in nonsurvivors. CONCLUSIONS. Initial lung dysfunction as indicated by respiratory indices does not predict the outcome in pediatric ARDS. The underlying disease, hemodynamic situation, and age have to be considered in relation to the degree of lung dysfunction to determine new therapeutic strategies such as extracorporeal support.

Estimation of nitrogen balance based on a six-hour urine collection in infants.

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 less than 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.