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Biomedical subjects

C J Newth

Publications and source records attributed to C J Newth.

At least 55 records · Page 3Linked to original sources
PubMed1991

Effect of positive end-expiratory pressure on respiratory compliance in children with acute respiratory failure.

We studied the effect of positive end-expiratory pressure (PEEP) on the compliance of the respiratory system (Crs) in 25 children (age, 3 weeks to 10 years) requiring mechanical ventilation. Functional residual capacity (FRC) measurements were performed at 2 cm H2O increments, from 0 to 18 cm H2O of PEEP, and the FRC values were regressed versus PEEP. Static Crs, Crs/kg, and specific compliance (Crs/FRC) were calculated for each PEEP level. When FRC normality was reached Crs/kg improved in 15/25 (60%) patients but decreased in 2/25 (8%). Overall, Crs/kg increased from a mean +/- SE of 0.94 +/- 0.09 to 1.35 +/- 0.13 mL/cm H2O/kg (P = 0.003) and Crs/FRC from a mean +/- SE of 0.067 +/- 0.006 to 0.077 +/- 0.007 mL/cm H2O/mL (P = 0.057). The maximum compliance (mean Max Crs/kg, 1.56 +/- 0.12 mL/cm H2O/kg, and mean Max Crs/FRC, 0.089 +/- 0.005 mL/cm H2O/mL) was significantly higher than the compliance at the clinically chosen PEEP level and the compliance at the PEEP that normalized FRC. Maximum compliance was achieved within 4 cm H2O of the PEEP that normalized FRC. In 14/25 (60%) of cases the PEEP at maximum compliance coincided with the PEEP that resulted in FRC normalization. We concluded that static respiratory compliance improves in most (but not all) children with acute respiratory failure when FRC is normalized. Static respiratory compliance reaches maximum levels at PEEP values that are close (but not equal) to those that result in FRC normalization. Thus, assessment of the effect of PEEP on compliance is required in individual patients.

Child↗
PubMed1991

Rib cage to abdominal asynchrony in children undergoing polygraphic sleep studies.

We assessed rib cage (RC) to abdominal (AB) asynchrony in 110 children, aged 1 to 50 months who underwent diagnostic daytime polygraphic sleep studies (PSG), and correlated the results. RC-AB asynchrony was calculated by the phase angle (PA) technique and compared to normal values (0-24 degrees) derived from a separate group of 45 control children, matched for age and weight. Eighty-two of the 110 patients had PSG as part of their evaluation for obstructive sleep apnea. There was a high association between the phase angles and the PSG results (P less than 0.01; Fisher's exact test). PSG was abnormal in 38/82 patients (46%) and the phase angle was increased in 51/82 (62%) (mean +/- SD, 68 degrees +/- 39 degrees; range 28 degrees - 168 degrees) compared to the normal controls (P less than 0.001). Fourteen of the 110 patients had bronchopulmonary dysplasia; of these, PSG and PA results agreed in six normal and seven abnormal studies and disagreed in only one (P = 0.002). Six of 110 patients had Down's syndrome; 5 of 6 had increased RC-AB asynchrony, compared to 3 of 6 who had abnormal PSG. Eight of 110 patients were evaluated for central apnea and hypoventilation; PA was abnormal in 4 of 8, who also had abnormal PSG and in 1 with normal PSG. We conclude that RC-AB measurement by the PA technique may be an important adjunct to the evaluation of breathing disorders during sleep in small children and it may be a good screening test for small children who need PSG.

Abdominal Muscles↗
PubMed1991

Outcome of oncology patients in the pediatric intensive care unit.

We evaluated the outcome of oncology patients in the Pediatric Intensive Care Unit (PICU) from a total of 72 consecutive admissions. Severity of illness and quantity of care were measured by the Physiologic Stability Index (PSI) and the Therapeutic Intervention Scoring System (TISS), respectively. The overall mortality was 51% and was especially high in patients admitted for acute organ system failure (OSF)-66%. Acute respiratory failure was the most frequent OSF (73%) and the most common cause for PICU admission. A poor outcome was associated with severe leucopenia (less than 1000 WBC/mm3, 91% mortality), acute renal failure (94% mortality) and central nervous system deterioration (83% mortality). When the outcome was predicted using a quantitative algorithm the observed mortality was significantly higher than the predicted for all admissions with a PSI higher than 5. Improved scoring systems are required to enable characterization of pediatric cancer patients admitted to the PICU.

Acute Kidney Injury↗
PubMed1991

Pharmacokinetics of dopamine in infants and children.

OBJECTIVE: We studied the pharmacokinetics of dopamine in hemodynamically stable children. DESIGN: Prospective clinical trial. SETTING: Pediatric ICU. PATIENTS: Children (age 3 months to 13 yrs) recovering from cardiac surgery or shock. INTERVENTION: Plasma dopamine concentrations were measured at the steady state or at termination of infusion using high-performance liquid chromatography. RESULTS: The half-lives of distribution and elimination were 1.8 +/- 1.1 and 26 +/- 14 (SD) mins, respectively. The apparent volume of distribution was 2952 +/- 2332 mL/kg. The clearance rate was 454 +/- 900 mL/kg.min. Dopamine clearance was linearly related to dose only in patients who were also receiving dobutamine (r2 = .76, p less than .05). Hepatic and renal dysfunction did not affect the pharmacokinetics of dopamine. CONCLUSIONS: A relationship between dopamine and dobutamine that affects the disposition of these two drugs may exist. The pharmacokinetics of dopamine are variable even in hemodynamically stable children. Hepatic or renal function does not adversely affect the pharmacokinetics of dopamine.

Child↗
PubMed1991

The ventilatory and oxygen costs in the anesthetized rhesus monkey of inhaling drugs used in the therapy and diagnosis of asthma.

We examined in male Rhesus monkeys the effects on oxygen consumption (VO2), carbon dioxide production (VCO2), minute ventilation (VE), heart and respiratory rates, and functional residual capacity (FRC) of breathing normal saline (NS), salbutamol (albuterol), methacholine (MCh), sodium cromoglycate (SCG), epinephrine (adrenaline), and terbutaline in doses commonly prescribed to human infants and children. We studied 10 anesthetized and intubated monkeys with a mean age and weight of 6.0 yr and 9.1 kg, respectively. VO2 increased over control, by 46.5% after salbutamol (p less than 0.0005), 25% after methacholine (p less than 0.001), 13.2% after epinephrine (p less than 0.01), and 16% after terbutaline (p less than 0.001), but it did not increase after either SCG or NS. VE increased by 82% after MCh and salbutamol (p less than 0.001), less dramatically after epinephrine and terbutaline at 50.5 and 31.5% (p less than 0.02 and p less than 0.001), respectively, and not at all after SCG and NS. Heart rate response was greatest after salbutamol, and nodal and ventricular arrhythmias were noted in four of 10 monkeys after MCh challenge. FRC did not change significantly except after salbutamol, where there was a small rise of 1.8 ml/kg (p less than 0.05).

Administration, Inhalation↗
PubMed1991

The effects of varying inflation and deflation pressures on the maximal expiratory deflation flow-volume relationship in anesthetized rhesus monkeys.

Deflation flow-volume curve analysis is a pulmonary function test sensitive to small airways dysfunction that is suitable for use in infants and children who are intubated. This test relies upon deflation flow-volume (DFV) curve analysis, which is a technique to obtain maximal expiratory flow-volume curves (MEFV) by forced deflation of the lungs in infants who are intubated. The method mimics the voluntary forced flow-volume curves that adults and older children undertake. We studied 10 anesthetized male Rhesus monkeys of the same weight as human infants but developmentally equivalent to older children. We reviewed the effects on forced deflation vital capacity (DVC) and flows at various subdivisions of vital capacity (PEF, MEF50, MEF25, MEF10) of systematically varying the required inspiratory and deflation pressure during the course of 56 consecutive deflation maneuvers. Inflation pressures of +40 and +50 cm H2O caused a marked but transient bradycardia along with a (probably spurious) short-lasting fall to 89% mean arterial oxygen saturation (SaO2). Increasing positive and negative pressures increased DVC and expiratory flows. The highest mean DVC was 75.6 +/- 1.3 ml/kg, PEF was 128.0 +/- 3.5, MEF50 was 85.9 +/- 2.2, MEF25 was 74.3 +/- 1.9, and MEF10 was 38.5 +/- 2.9 ml/kg/s, all obtained at the pressure gradient of 90 cm H2O (+50/-40 cm H2O) at the start of the deflation maneuver. At this gradient, the intraindividual coefficients of variation were: DVC = 0.8%, PEF = 3.1%, MEF50 = 2.2%, MEF25 = 2.1%, MEF10 = 5.4%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Adult respiratory distress syndrome in severely neutropenic children.

It has been suggested that polymorphonuclear cells (PMNs) are required for the development of the adult respiratory distress syndrome (ARDS). We investigated the occurrence of ARDS with acute respiratory failure in 30 children with severe neutropenia (less than 500 PMNs/mm3) who met the clinical diagnostic criteria for ARDS and in whom postmortem histopathology findings were available within 7 days of the onset of ARDS. In 26 patients the histopathology was consistent with ARDS. In 12/26 children no white blood cells (WBC) were found in the lung tissue, 10/26 had moderate infiltration of mononuclear cells, 2/26 had massive tumor cell infiltration, and in 2/26 PMNs were found. Thus, in at least 22/26 patients ARDS developed without neutrophilic infiltration of the lungs. The maximum active lung infection rate was found to be 69% (18/26) by endotracheal and post mortem lung cultures and histology. Thus 5/26 children had ARDS without any WBC in the lung tissue. We conclude, as have other studies in adults that the absence of PMNs does not protect children from the development of ARDS and that the mechanism which involves PMNs is probably only one of several pathways for diffuse alveolar damage, some of which is neutrophil-independent.

Adolescent↗
PubMed1990

Varying tracheal cross-sectional area during respiration in infants and children with suspected upper airway obstruction by computed cinetomography scanning.

An ultrafast cinetomography computed tomographic scanner (cine-CT) was used to evaluate infants and children (n = 15) with suspected obstruction of the larynx or trachea. One scan sequence provided a single image at each of eight cross-sectional levels (volume-mode study). Each study, lasting 224 ms, covered the distance between the supraglottic area and the carina. Each patient also underwent a "dynamic" study at a specific level of interest determined from the volume-mode study. Forty images within 2.3 s covered at least one respiratory cycle. The images were displayed as a closed-loop movie and dynamic changes in laryngeal and tracheal caliber with respiration were monitored and quantitated. Tracheal boundaries were outlined either by a trackball-guided cursor (freehand) or semi-automated computer edge detection, and cross-sectional areas and diameters were determined. Reproducibility was tested among three investigators' freehand drawings and two automated computer drawings, at the same and at varying image intensities. The coefficient of variation for the computer-assisted records (0.2%) was smaller than for the best freehand drawing (1.5%). Tracheal diameters were reproducible, but with greater intra-individual investigator variability. Four normal tracheas had close to published measurements with conventional CT scanners. Cine-CT gives objective tracheal dimensions and their variation during respiration; it provides good anatomical detail above the carina, and also of the extra- and intra-thoracic vessels if injected with contrast medium.

Adolescent↗
PubMed1990

A double-blind, randomized study of sodium cromoglycate versus placebo in patients with cystic fibrosis and bronchial hyperreactivity.

To evaluate the effects of sodium cromoglycate (SCG) on patients with cystic fibrosis (CF) and with bronchial hyperreactivity, a long-term, double-blind, placebo-controlled, crossover study was performed. Fourteen patients with CF and without asthma (aged 7 to 29 years) and with bronchial hyperreactivity entered the study. Each patient received 8 weeks of 1% SCG nebulizer solution three to four times daily and 8 weeks of placebo. Seven patients received the treatment in the order SCG/placebo and seven patients in the reverse order. Evaluation of SCG effect was performed every 4 to 8 weeks by (1) clinical assessment of symptoms, (2) clinician and patient/parent opinion, (3) pulmonary function tests, and (4) methacholine provocation tests. After two patients were withdrawn for lack of cooperation, the results were evaluated for treatment effect (SCG versus placebo), period effect (whether SCG was administered first or last), or combination of both. No significant difference was found for these parameters for the clinical assessment of symptoms, the patient/parent and clinician opinion, their subjective preferences, the metacholine challenges, or the pulmonary function tests. The study did not demonstrate any benefit from the use of SCG in patients with CF and with bronchial hyperreactivity and does not support the routine use of SCG in patients with CF.

Adolescent↗
PubMed1990

Factors affecting accidental extubations in neonatal and pediatric intensive care patients.

All patients intubated in the neonatal (NICU) and pediatric (PICU) ICUs over a 3-yr period were evaluated prospectively to determine the incidence of accidental extubation (AE) and contributing factors. Two thousand two hundred patients (age range 26 wk gestation to 18 yr) were intubated for a total of 21,222 days. In the PICU and NICU, a total of 153 patients experienced 195 AE. The PICU had 113 AE in 1,388 subunit for a rate of 1.15 AE/100 intubated days. The NICU had 82 AE in 812 intubated patients, a rate of 0.72 AE/100 intubated days. A review of factors contributing to AE showed the most critical to be: sedation not administered in the 2 h before AE (65%), the lack of two-point or more restraints (58%), and the performance of a patient procedure at the bedside (49%). One death occurred as an indirect consequence of AE. The data are being reported as a function of number of days intubated in an attempt to standardize reporting techniques. The use of standardized reporting and the identification of high-risk factors may be useful for education and modification of patient care practices.

Adolescent↗
PubMed1990

Thoracoabdominal asynchrony in acute upper airway obstruction in small children.

The assessment of the severity and response to therapy of acute upper airway obstruction (UAO) in small children relies on subjective parameters. Using a noncalibrated respiratory inductance plethysmograph (RIP), we quantitated the rib cage (RC) to abdominal (AB) asynchrony and the lag phase in chest wall expansion by the phase angle from the RC versus AB signal curve. Phase angles were obtained in 17 children aged 1 to 50 months with acute UAO and 30 normal control subjects. The phase angle in UAO (16 to 165 degrees; mean = 83.6 degrees) was significantly higher than in control subjects (3 to 25 degrees; mean = 11.5 degrees), p less than 0.001. Following 29 episodes of inhalation treatment with 0.03 ml/kg of racemic epinephrine, the phase angle in the UAO group decreased to 7 to 160 degrees (mean = 38.3; p = 0.001) as the shape of the RC versus AB loop became narrower. In response to the treatment, the clinical severity of UAO decreased and the tidal breathing flow-volume loop improved. A high association was observed between the phase angle and the degree of stridor (p less than 0.005 Fisher's exact test), and in 90% (26 of 29) the changes in the phase angle and in the degree of stridor were in agreement. We conclude that the RC-AB asynchrony in acute UAO can be objectively quantitated by phase-angle measurement from a noncalibrated RIP and is thus suitable for use in infants and small children. The phase angle may be used to assess objectively the response of UAO to therapy.

Abdomen↗
PubMed1990

An automated bedside method for measuring functional residual capacity by N2 washout in mechanically ventilated children.

Beside measurement of functional residual capacity (FRC) in ventilated children is impractical. Using a simple technique based on open circuit N2 washout, we measured FRC in ventilated children. The system was evaluated in the laboratory and in patients. Using a mechanical lung, the reproducibility of 200 studies over a range of 100-500 mL at each of four different flow rates (10 determinations at each level) was very high with a mean coefficient of variation of 2.3% (range 0.5-5.1%). Linearity of the integrated N2 signal for volumes of 100-500 mL washed out at different flow rates was excellent (range 7.4-17.9 L/min), r = 0.99. The mean difference between measured and preset mechanical lung volumes was 2.4% (range 0-4.6%). In vivo, reproducibility of six to 10 FRC determinations in each of 30 children gave a mean coefficient of variation of 2.7%. Comparison to the conventional Douglas bag collection method showed a high correlation (r = 0.97). We conclude that this is an easy, highly reproducible, and accurate method for FRC determination suitable to ventilated infants and children.

Child↗
PubMed1990

Functional residual capacity in ventilated infants and children.

Positive end expiratory pressure (PEEP) is an accepted treatment for children with acute respiratory failure secondary to restrictive lung diseases. Using a simple technique based on open circuit nitrogen washout, we determined the functional residual capacity (FRC) in 25 ventilated children (age 3 wk-10 y) with acute respiratory failure secondary to restrictive lung disease (pulmonary edema, bilateral pneumonia). FRC measured at a physiologic level of PEEP (2-4 cm H2O) was 45.0 +/- 3.6% (mean +/- SEM; range 12-80%) lower than normal predicted values. At the PEEP level chosen clinically (4-10 cm H2O, mean = 6.0), the FRC was below normal predicted values for nonintubated children by a mean of 31.8% (range 0-73%) (p = 0.0001) and only seven patients (28%) had FRC within 20% below predicted normal values. FRC normalized at PEEP levels of 6-18 cm H2O (mean = 11.6), which was up to 200% above the clinically chosen PEEP level. In six children without lung disease who were ventilated at a PEEP level of 2-4 cm H2O, the FRC was within normal range in two, but significantly higher (by 45%) in the other four. We conclude that FRC in ventilated children with acute restrictive lung disease is significantly lower than normal and the clinically chosen PEEP fails to normalize the FRC in most of the cases.

Child↗
PubMed1989

In vitro performance of the small particle aerosol generator (SPAG-2).

The anti-viral drug ribavirin primarily used for the treatment of respiratory syncytial virus (RSV) infection in infants is delivered by continuous nebulization with the Small Particle Aerosol Generator (SPAG). Clinical data suggest that the SPAG is an efficient nebulizer for ribavirin; it is also being used for the delivery of other pulmonary agents. The efficiency of a nebulizer can be defined in large part by delivering a major proportion of its output with a particle size of 1 to 5 microns which is small enough to penetrate the tracheobronchial tree. We assessed both the quality and quantity of the SPAG aerosol cloud with the aid of a multistage liquid impinger, utilizing 2% ribavirin and 1% cromolyn sodium solutions. The aerosol of either solution had a mass median aerodynamic diamter (MMAD) of approximately 1.2 microns, and this seemed insensitive to solution strength and nebulization period. Of the solutions of ribavirin and cromolyn sodium 92.3% and 95.0%, respectively, by weight of delivered particles, had aerodynamic diameters less than 5 microns and about 70-75% of the aerosol particles had an aerodynamic diameter in the 1-5 microns range. This implies that the aerosol cloud is adequate for delivery through a ventilator circuit. Performance was maintained over long (16 hours), continuous periods of delivery. The SPAG could be useful for delivery of other respiratory drugs by continuous nebulization.

Aerosols↗
PubMed1989

Influence of food on the absorption of albuterol Repetabs.

A study was conducted in 12 healthy, nonsmoking male volunteers to examine the effect of food intake on the absorption profile of albuterol repeat-action tablets. This randomized crossover study consisted of two phases separated by a 1-week washout period. All subjects fasted 10 hours preceding drug administration. Each subject received two 4 mg albuterol repeat-action tablets with and without a high fat content breakfast. Plasma albuterol concentrations were determined by a gas chromatographic/mass spectrophotometric assay. Relative bioavailability was assessed by comparing areas under the plasma-albuterol concentration time curves as well as peak concentrations and time to peak concentration. No significant differences were noted between the two treatment phases in the area under the curve or peak plasma concentrations. The areas under the curve were 100 and 105 hr.ng/ml when the drug was administered with and without food, respectively. The corresponding peak plasma concentration values were 9.4 and 10.4 ng/ml, respectively. The only significant difference observed was in the maximum time to reach peak plasma concentrations, which was delayed by about 1 hour when the drug was administered with food. Therefore, food has minimal effect on the absorption of albuterol from repeat-action tablets.

Adult↗
PubMed1989

Vecuronium by continuous infusion for neuromuscular blockade in infants and children.

Vecuronium's short half-life and minimal cardiopulmonary side-effects make it a suitable drug for continuous infusion. Vecuronium is used frequently in critically ill patients to increase their total compliance and to minimize the adverse effects of mechanical ventilation. This crossover, prospective study evaluates the use of vecuronium by continuous infusion vs. hourly boluses. Patients were assigned randomly to either method; 12 h later each group was transferred to the other method. Neuromuscular blockade (NMB) was followed with the Train-of-Four method. Cardiopulmonary variables were followed hourly. The total dosage/kg body weight was calculated for each method. Six patients were started with continuous drip and the other six with hourly boluses. There were no significant differences in the cardiopulmonary variables through the two periods, although statistically there was a significant difference in the total dosage/kg body weight required for each method. The mean of total vecuronium used in the drip was 0.79 mg/kg.12 h (range 0.1 to 1.8). The mean of the hourly boluses was 1.34 mg/kg.12 h (range 1.0 to 2.55). Patients on continuous infusion required less vecuronium to maintain a similar NMB (p less than .01).

Adolescent↗
PubMed1987

Pyruvate dehydrogenase complex deficiency as a cause of subacute necrotizing encephalopathy (Leigh disease).

Leigh disease is a disorder with great clinical variability and for which diverse biochemical causes have been proposed. Clarification requires rigorous correlation of biochemical abnormalities with strict morphologic diagnosis; such an unambiguous association is the subject of this report. A patient with well-documented clinical and biochemical pyruvate dehydrogenase complex deficiency is shown on postmortem examination to have the specific CNS pathology of Leigh disease. These findings, considered together with the aggregate data in the literature, suggest strongly that pyruvate dehydrogenase complex deficiency is the basic defect in a subgroup of patients with Leigh disease.

Acidosis, Lactic↗