Use of cloud radar Doppler spectra to evaluate stratocumulus drizzle size distributions in large-eddy simulations with size-resolved microphysics.

A case study of persistent stratocumulus over the Azores is simulated using two independent large-eddy simulation (LES) models with bin microphysics, and forward-simulated cloud radar Doppler moments and spectra are compared with observations. Neither model is able to reproduce the monotonic increase of downward mean Doppler velocity with increasing reflectivity that is observed under a variety of conditions, but for differing reasons. To a varying degree, both models also exhibit a tendency to produce too many of the largest droplets, leading to excessive skewness in Doppler velocity distributions, especially below cloud base. Excessive skewness appears to be associated with an insufficiently sharp reduction in droplet number concentration at diameters larger than ~200 µm, where a pronounced shoulder is found for in situ observations and a sharp reduction in reflectivity size distribution is associated with relatively narrow observed Doppler spectra. Effectively using LES with bin microphysics to study drizzle formation and evolution in cloud Doppler radar data evidently requires reducing numerical diffusivity in the treatment of the stochastic collection equation; if that is accomplished sufficiently to reproduce typical spectra, progress toward understanding drizzle processes is likely.

Effect of neuromuscular blockade on oxygen consumption and energy expenditure in sedated, mechanically ventilated children.

OBJECTIVE: To quantify the effects of neuromuscular blockade (NMB) on energy expenditure for intubated, mechanically ventilated, critically ill children. DESIGN: A prospective, unblinded clinical study. Each subject was studied twice, before and after establishment of NMB. SETTING: A tertiary care pediatric intensive care unit. PATIENTS: Critically ill children undergoing mechanical ventilation and receiving ongoing sedation were eligible, if they had a cuffed endotracheal tube and were physiologically stable. INTERVENTIONS: A total of 20 children (age, 1 to 15 yrs) were studied in an unblinded, crossover fashion. All were mechanically ventilated via a cuffed endotracheal tube, with ventilator rate and tidal volume adequate to provide complete ventilation, and F(IO2) <0.6. Absence of gas leak around the endotracheal tube was assured, and all patients were sedated using continuous infusions of midazolam and/or fentanyl; no changes in ventilator settings, nutritional input, or inotropic drug dose were permitted during the study period. Each patient underwent indirect calorimetry immediately before establishment of NMB. NMB was then induced, and indirect calorimetry was repeated. Complete blockade was verified using a peripheral nerve stimulator. In each case, the two sets of measurements were completed within a 1-hr period. MEASUREMENTS AND MAIN RESULTS: Data analyzed included identifying and diagnostic information, oxygen consumption, and carbon dioxide production. Energy expenditure was calculated using standard formulas. Oxygen consumption and energy expenditure values obtained before and after the establishment of NMB were compared by using paired Student's t-test. NMB reduced oxygen consumption from 6.54+/-0.49 mL/kg/min to 5.90+/-0.40 ml/kg/min, and energy expenditure was reduced from 46.5+/-3.7 kcal/kg/24 hrs to 41.0+/-2.8 kcal/kg/24 hrs (p < .001 in each case). The reduction in oxygen consumption was 8.7+/-1.7%, and that in energy expenditure 10.3+/-1.8%, of pre-NMB values, respectively. CONCLUSION: NMB significantly reduces oxygen consumption and energy expenditure in critically ill children who are sedated and mechanically ventilated; the degree of reduction is small.

Nonradiographic assessment of enteral feeding tube position.

OBJECTIVE: To determine whether a clinical, nonradiographic criterion can be used to predict when the tip of a blindly placed feeding tube is in the small intestine. DESIGN: Prospective sample. SETTING: Pediatric intensive care unit at a tertiary care children's hospital. PATIENTS: Critically ill children requiring transpyloric feeding. INTERVENTIONS: The small bowel was intubated, using a blind, bedside transpyloric feeding tube placement protocol. The feeding tube was considered to be in the small bowel when <2 mL of a 10- mL aliquot of insufflated air could be aspirated from the feeding tube. This clinical criterion was confirmed with an abdominal radiograph. MEASUREMENTS AND MAIN RESULTS: Patient age ranged from 1 month to 19 yrs (median 6 months). Weight ranged from 2.2 to 60 kg (median 4.9). Median time to feeding tube placement was 10 mins (range 5 to 60). Eighty-nine percent of the patients were mechanically ventilated, while 28% of these patients were pharmacologically paralyzed. Seventy-five feeding tubes were inserted. There were no known complications. Ninety-nine (74/75) percent of the feeding tubes were positioned in the small bowel. The inability to aspirate insufflated air correctly predicted small bowel intubation with 99% certainty (Sequential Probability Ratio Test, p = .05 and power = .80). This test incorrectly predicted the position of only one feeding tube, the 26th, which was in the stomach. Of the 74 feeding tubes positioned in the small bowel, 13 feeding tubes were in the duodenum and 61 were in the jejunum. CONCLUSIONS: The inability to aspirate insufflated air confirms the transpyloric position of a feeding tube. Other clinical criteria did not successfully predict small bowel intubation. Use of this single test may obviate confirmatory abdominal radiographs in carefully selected patients and may lead to more cost-effective and timely initiation of enteral feedings.

Comparison of simultaneously obtained arterial and capillary blood gases in pediatric intensive care unit patients.

OBJECTIVE: To determine whether capillary blood gas measurements provide a clinically acceptable estimate of arterial pH, PCO2, and PO2. DESIGN: Prospective convenience sample. SETTING: Pediatric intensive care unit at a referral children's hospital. PATIENTS: Fifty children > 1 month of age with indwelling arterial catheters. INTERVENTIONS: A local anesthetic was applied to the third finger of the hand contralateral to a radial artery catheter. After 90 mins, simultaneous arterial and capillary blood gases were drawn. MEASUREMENTS AND MAIN RESULTS: Arterial and capillary pH, PcO2, and PO2 were measured. Heart rate and Wong/Baker faces score were noted before and during capillary blood gas collection to assess discomfort associated with blood collection. There was a strong correlation between capillary and arterial pH (r2 = .903, p < .0001). The relative average bias of the capillary pH was 0.009, with capillary lower than arterial and 95% limits of agreement of +/- 0.032. In all patients, the absolute value of the difference between arterial and capillary pH was < or = 0.05. There was a strong correlation between arterial and capillary PCO2 (r2 = .955, p < .0001). The relative average bias of the capillary PCO2 was 1.6 torr (0.21 kPa), with capillary higher than arterial and 95% limits of agreement of +/- 4.5 torr (+/- 0.6 kPa). In two of 50 patients, the absolute value of the difference between arterial and capillary PCO2 was > 6.5 torr (> 0.87 kPa). Despite a statistically significant correlation between capillary and arterial PO2 (r2 = .358, p < .0001), the absolute value of the difference between arterial and capillary PO2 was > 6.5 torr (> 0.87 kPa) in 42 of 50 patients. Pain, endotracheal intubation, vasoactive drips, or pharmacologic paralysis did not affect accuracy of the capillary pH or PCO2. CONCLUSIONS: Capillary blood gases accurately reflect arterial pH and PCO2 in most pediatric intensive care unit patients. Capillary samples did not significantly underestimate arterial hypercarbia or acidosis. This conservative reflection of metabolic status may be particularly useful in hemodynamically stable patients with mild-to-moderate lung disease.

A randomized, controlled study of the 1-hour and 24-hour effects of inhaled nitric oxide therapy in children with acute hypoxemic respiratory failure.

STUDY OBJECTIVE: To determine whether 24 h of inhaled nitric oxide improves oxygenation greater than conventional therapy alone in children with acute hypoxemic respiratory failure. DESIGN: Prospective, randomized, controlled study. SETTING: Twenty-six-bed pediatric ICU in a tertiary children's hospital. PATIENTS: Twenty-four patients with acute bilateral lung disease requiring a positive-end expiratory pressure >6 cm H2O and a fraction of inspired oxygen >0.5 for >12 h. INTERVENTIONS: Twelve patients were treated with 10 ppm inhaled nitric oxide from the onset of randomization and 12 control patients were initially maintained on a regimen of conventional therapy alone. After a period of 24 h, control patients were also treated with 10 ppm inhaled nitric oxide. Hemodynamic and blood gas measurements were performed at baseline, at 1 h after randomization, and at 24-h intervals for 2 days. MEASUREMENTS AND RESULTS: Inhaled nitric oxide decreased the ratio of pulmonary to systemic vascular resistance and improved oxygenation indexes during the initial hour following randomization. However, 24 h after randomization, the oxygenation indexes of 11 surviving treated patients were not improved in comparison to baseline or the oxygenation indexes of 10 surviving control patients. Oxygenation indexes acutely improved in control patients when inhaled nitric oxide was started after 24 h of conventional therapy. Oxygenation indexes remained improved in the initial control patients after 24 h of inhaled nitric oxide. CONCLUSIONS: Pulmonary vascular resistance and systemic oxygenation are acutely improved by 10 ppm inhaled nitric oxide in some children with severe lung disease. However, a sustained improvement in oxygenation may not occur during prolonged therapy. Thus, inhaled nitric oxide may have a limited therapeutic role in children with acute hypoxemic respiratory failure.

Metabolic measurements during mechanical ventilation in the pediatric intensive care unit.

The metabolism of critically ill infants and children is significantly influenced by their underlying diseases, and standard predictive equations result in inappropriate nutritional support in most of these patients. Furthermore, significant day-to-day variability in energy expenditure may be present in individual patients. Inadequate or excessive energy supply can adversely affect the clinical course of many critically ill patients. For these reasons, serial measurements of energy expenditure should be considered whenever accurate determination of energy needs is deemed necessary. With the wide availability of proprietary metabolic carts suitable for use in mechanically ventilated pediatric patients, serial metabolic measurements via indirect calorimetry are feasible in most critically ill infants and children. The use of indirect calorimetry should also be considered in this population to assess changes in oxygen consumption and the relationship of oxygen consumption to oxygen delivery in response to changes in therapy, such as manipulation of cardiac output using vasoactive medications, or during weaning of mechanical ventilation.

Eliminating sleep-associated hypoxemia improves growth in infants with bronchopulmonary dysplasia.

OBJECTIVE: Infants with bronchopulmonary dysplasia (BPD) have been previously reported to have a decrease in growth velocity after stopping supplemental oxygen (SO). SO was stopped after a short-term recording (20-30 minutes) of pulse oxygen saturation (Sao2) of 92% or greater in room air. Other studies have documented that Sao2 decreases further during feedings and sleep in infants with BPD. Two questions were asked: (1) whether short-term, awake Sao2 studies would reliably predict prolonged sleep Sao2; and (2) how Sao2 sustained at 88% to 91% vs 92% or greater in room air would impact growth velocity in infants with BPD. METHODOLOGY: Short-term Sao2 studies were prospectively compared with prolonged sleep Sao2 (n = 63) and the growth velocity of infants who had SO discontinued after a prolonged sleep Sao2 recording of 88% to 91% (group 1; n = 14) versus 92% or greater (group 2; n = 34) in room air. RESULTS: Failure to maintain Sao2 at predetermined levels occurred in 18 (29%) of 63 infants during their first prolonged sleep study. There was no correlation between short-term awake Sao2 and prolonged sleep Sao2 recordings (r = .02). Body weight, height, weight for height, and rate of weight gain were similar for all study infants before SO was stopped and remained constant for group 2 infants after SO was stopped. However, group 1 infants had a significant decrease in the rate of weight gain (17.3 +/- 13.1 vs 3.7 +/- 6.1 g/kg per day), and the mean z scores for weight gain and weight for height also decreased significantly for group 1 infants. Energy intake, incidence of acute infection, hematocrit values, and medication use did not differ before or after stopping SO in either group. CONCLUSIONS: This study indicated that short-term, awake Sao2 measurements do not predict prolonged sleep Sao2, and overall, infants with BPD continued a positive growth trend when Sao2, remained greater than 92% during prolonged sleep.

Analysis of the variability in the pharmacokinetics and pharmacodynamics of bumetanide in critically ill infants.

OBJECTIVES: Account for the interindividual variability in the pharmacokinetics and pharmacodynamics of bumetanide after intravenous administration of single doses to critically ill infants. METHODS: This prospective open-label study was carried out in the pediatric intensive care unit of a university-based children's hospital. Fifty-three volume-overloaded critically ill infants (age range, 4 days to 6 months) were divided into two groups: those with heart disease (31 infants) and those with lung disease (22 infants). Each patient received a single intravenous bolus dose of bumetanide. Doses, selected in sequential order, ranged from 0.005 to 0.100 mg/kg. Age was used as a continuous variable to determine its effects on the variability in the pharmacokinetics and pharmacodynamics of bumetanide. Hierarchical multiple regression analyses were used to assess the effects of age, disease, and other drugs on the variability in the effects of bumetanide. RESULTS: Total clearance, renal clearance, and nonrenal clearance of bumetanide all increased with age (p < 0.05), but the ratio of renal clearance to total clearance remained constant at about 0.4. Half-life and mean residence time decreased markedly in the first month of life (p < 0.05). Bumetanide excretion rate normalized for dose also increased with increasing age. Patients with lung disease exhibited a significantly greater clearance and shorter half-life (p < 0.05) than those with heart disease, whereas volume of distribution was similar in both groups. The primary determinant of bumetanide excretion rate was the administered dose (73%). Dose-response curves for urine flow rate and electrolyte excretion were similar between disease groups. The time course of the effect of bumetanide excretion rate on pharmacodynamics responses was similar between disease groups, as was the duration of the diuretic effect. CONCLUSIONS: The pharmacokinetics of bumetanide were influenced significantly by age and disease. Differences in pharmacokinetics between patients with lung and heart disease were primarily due to differences in total clearance. The administered dose of bumetanide and age were positive determinants of bumetanide excretion rate and pharmacodynamic responses. Pharmacodynamic responses as a function of bumetanide excretion rate were not significantly different between disease groups.

Pharmacokinetics of bumetanide in critically ill infants.

OBJECTIVE: Define the pharmacokinetics of bumetanide after single intravenous doses in volume-overloaded critically ill infants. METHODS: A prospective, open-label study was carried out in a group of 58 infants aged 0 to 6 months who required diuretic therapy. Each patient received a single dose of intravenous bumetanide. Doses selected in sequential order ranged from 0.005 to 0.10 mg/kg. Hematologic and serum chemistry studies were performed before and at 6 and 24 hours after bumetanide administration. Determinations of urine volume and chemistries were performed before (collected from -2 to -4 hours to time 0) and at 1, 2, 3, 4, 6, and 12 hours after bumetanide dosing. Serum samples collected at time 0 and at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minutes and urine collected at time 0 and at 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12 hours were analyzed for bumetanide concentration. Data were evaluated by standard noncompartmental pharmacokinetic techniques. RESULTS: Peak serum bumetanide concentrations occurred at 5 minutes after bumetanide administration. Area under the curve and peak serum bumetanide concentrations showed linear increases over the twentyfold dose range; whereas beta volume of distribution, volume of distribution at steady state, clearance, renal clearance, half-life, and mean residence time values were independent of dose. Peak urinary excretion rates of bumetanide increased linearly with increasing doses. The mean percent of bumetanide recovered in the urine from 0 to 12 hours was 40% +/- 15% of the administered dose. CONCLUSIONS: Distribution and elimination kinetics of bumetanide were similar in all patients. Elimination kinetics were first order over the dose range of 0.005 to 0.10 mg/kg. Pharmacokinetic parameter estimates (beta volume of distribution, volume of distribution at steady state, clearance, renal clearance, half-life, and mean residence time) were independent of the dose of bumetanide administered. Single doses of bumetanide up to 0.10 mg/kg appear to be well tolerated in acutely ill volume-overloaded infants aged 0 to 6 months.

Dose-ranging evaluation of bumetanide pharmacodynamics in critically ill infants.

OBJECTIVES: Determine the diuretic effects of single intravenous doses of bumetanide in volume-overloaded critically ill infants. METHODS: A prospective, open-label study was carried out in 56 infants aged 0 to 6 months who required diuretic therapy. Each patient received a single intravenous dose of bumetanide. Doses selected in sequential order ranged from 0.005 to 0.10 mg/kg. Determinations of urine volume, electrolytes, creatinine levels, and osmolality were performed before (collected from -2 to -4 hours to time 0) and at 1, 2, 3, 4, 6, and 12 hours after bumetanide dosing. Serum samples collected at time 0 and at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minutes and urine aliquots collected at time 0, 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12 hours were analyzed for bumetanide concentration. Individual changes in urine flow rate and electrolyte excretion were plotted against corresponding bumetanide excretion rates, taken as the effective dose of the drug. RESULTS: Peak bumetanide excretion rates increased linearly with increasing doses of drug. Time course patterns for urine flow rate and electrolyte excretion were similar for all dosage groups. Urine flow rate and electrolyte excretion increased linearly up to a bumetanide excretion rate of approximately 7 micrograms/kg/hr and either plateaued (urine flow rate) or declined at a bumetanide excretion rate of > 10 micrograms/kg/hr. Diuretic efficiency of bumetanide was maximal at doses of 0.005 to 0.010 mg/kg but decreased at higher doses. CONCLUSIONS: Maximal diuretic responses occurred at a bumetanide excretion rate of about 7 micrograms/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a proportionately higher bumetanide excretion rate but no increased diuretic effect. Lower doses of bumetanide had the greatest diuretic efficiency, suggesting that continuous infusion of low doses of bumetanide or intermittent low-dose boluses may produce optimal diuretic responses in critically ill infants.

Racemic versus l-epinephrine aerosol in the treatment of postextubation laryngeal edema: results from a prospective, randomized, double-blind study.

OBJECTIVE: To determine whether any advantage exists using racemic epinephrine instead of the more potent and less expensive levo(1)-epinephrine in the treatment of postextubation laryngeal edema. DESIGN: Prospective, double-blind, randomized study. SETTING: Pediatric intensive care unit in a university teaching hospital. PATIENTS: Twenty-eight patients with stridor during the immediate postextubation period. INTERVENTIONS: After extubation, patients demonstrating clinically important stridor were randomized in a double-blind fashion to receive an aerosol containing either 2.25% racemic or 1% l-epinephrine. MEASUREMENTS AND MAIN RESULTS: Heart rate, respiratory rate, blood pressure, and stridor score were determined at 20, 40, and 60 mins and 4 and 8 hrs after the initial aerosol administration. Patients in both groups demonstrated significant (p < .01) reductions in stridor score after aerosol administration. No significant differences were observed between treatment groups in improvement in stridor score or the number of subsequent aerosols required. Respiratory rate decreased significantly 40 and 60 mins after l-epinephrine but not after racemic epinephrine. No significant change in heart rate or blood pressure occurred after aerosol administration in either group. CONCLUSIONS: These data suggest that aerosolized l-epinephrine is as effective as aerosolized racemic epinephrine in the treatment of postextubation laryngeal edema without additional adverse side effects. When dosed appropriately, l-epinephrine is a less expensive and more widely available alternative to racemic epinephrine for the treatment of postextubation laryngeal edema.

Prolongation of inspiration during lower airway occlusion in children.

Inspiration is strongly inhibited by volume-related vagal afferents in human neonates and animals, but this reflex is not as active in human adults during normal breathing. To determine whether volume-related inspiratory inhibition occurs beyond the neonatal period, we performed 10 +/- 1 end-expiratory occlusions in nine asleep children, ages 2-29 mo, with cuffed tracheostomy or endotracheal tubes in place. Airflow, tidal volume, occlusion pressure, and surface diaphragm electromyogram (DIA EMG) were simultaneously recorded. Occlusion consistently increased mechanical (P less than 0.002) and neural inspiratory times (P less than 0.001). During occluded respiratory efforts, peak amplitude of DIA EMG increased by 22 +/- 10% (P less than 0.002). In contrast, initial rate of rise of DIA EMG did not change. We conclude that in children with isolated lower airways, end-expiratory occlusions prolonged inspiratory duration as measured by both mechanical and neural parameters. The lack of an associated increase in rate of rise of DIA EMG strongly suggests that inspiration is prolonged by release of volume-related inhibition of inspiration rather than by facilitation. These data provide evidence for the presence of the Hering-Breuer reflex beyond the neonatal period.

Diuretic therapeutics in the pediatric patient.

Careful management of fluid and electrolytes has long been an intrinsic part of pediatric practice. However, the augmentation of these manipulations through the rational use of diuretic agents requires considerable skill. In pediatric medicine, the regulation of pharmacokinetic processes and their interface with pharmacodynamic processes show dramatic age-related changes. These ontogenetic processes and their modification by various disease states must be considered carefully before selection and application of diuretic agents. The available data concerning the ontogeny of renal function and the attempts to apply diuretic therapy to pediatric disease are reviewed. It is concluded that results obtained to date suffer from the absence of a rigorous attempt to answer the fundamental therapeutic questions: What drug? What dose? What duration of therapy? A rational "target-effect" strategy is proposed for the application of diuretic agents to pediatric medicine.

Outcome of pediatric resuscitation.

A one-year prospective study of 105 resuscitations in 74 children was done at Milwaukee Children's Hospital. Resuscitation outcome was correlated to location of arrest, level of monitoring at time of arrest, and type of arrest. Type of arrest was the only analyzed variable that influenced outcome. This study indicates that outcome for children requiring resuscitation for respiratory arrest without cardiac arrest is reasonably good (25% mortality). However, the outcome for children requiring resuscitation for cardiac or cardiorespiratory arrest is poor (87% to 89% mortality or severe morbidity). Children who suffered a respiratory arrest without cardiac arrest had a better outcome than did adults. However, children who had a cardiac or cardiopulmonary arrest had the same poor outcome as did adults.