Sequential ciprofloxacin therapy in pediatric cystic fibrosis: comparative study vs. ceftazidime/tobramycin in the treatment of acute pulmonary exacerbations. The Cystic Fibrosis Study Group.

BACKGROUND: Cystic fibrosis patients have chronic bacterial infections of the respiratory tract, most commonly Pseudomonas aeruginosa. Although controversial, administration of antibiotic therapy during acute pulmonary exacerbations is standard practice. Fluoroquinolones are currently not indicated for use in young children because of the observation of arthropathy and damage to growing cartilage in beagle puppies. Because of its activity against P. aeruginosa and excellent oral bioavailability, ciprofloxacin offers a unique therapeutic alternative for this patient population. OBJECTIVE: This prospective, randomized, double blind study compared the efficacy and safety of sequential intravenous/oral ciprofloxacin vs. ceftazidime/tobramycin in hospitalized pediatric cystic fibrosis patients with an acute pulmonary exacerbation associated with P. aeruginosa infection. METHODS: One hundred thirty patients (ages 5 to 17 years) were randomized to receive either i.v. ciprofloxacin 10 mg/kg every 8 h for 7 days followed by oral ciprofloxacin 20 mg/kg every 12 h for a minimum of 3 days or i.v. ceftazidime 50 mg/kg every 8 h plus i.v. tobramycin 3 mg/kg every 8 h for a minimum of 10 days. Clinical, bacteriologic and safety responses were assessed throughout the study. RESULTS: All 84 patients (median age, 11 years; range, 5 to 17 years) valid for efficacy in both treatment groups demonstrated clinical improvement. Five patients experienced clinical relapses (3 ciprofloxacin, 2 ceftazidime/tobramycin) by the 2- to 4-week follow-up. Intent-to-treat analysis demonstrated similar clinical findings between the two treatment groups at both the end of therapy and follow-up. Clinical improvement correlated with improvement in pulmonary function studies and the acute clinical scoring system but not with bacteriologic eradication of Pseudomonas. DNA profiles demonstrated that irrespective of colony morphology, usually one clonal strain was associated with each patient's pulmonary exacerbation. Treatment-associated musculoskeletal events occurred with equal frequency (22% vs. 21%) in both study drug groups (n = 129), and arthralgias were within the range of rates for cystic fibrosis arthropathy. None of these events required study drug discontinuation. CONCLUSION: Sequential i.v./oral ciprofloxacin monotherapy offers a safe and efficacious alternative to standard parenteral therapy for acute pulmonary exacerbations in pediatric cystic fibrosis patients.

Effects of dexamethasone on pulmonary function following extubation.

Dexamethasone is often given to intubated neonates to facilitate successful extubation. To study the effects of dexamethasone on pulmonary function immediately following extubation, we conducted a randomized, blinded, placebo-controlled trial in 51 infants. All infants had been intubated for a minimum of 3 days but no more than 30 days. Mean weight at extubation was 2.41 kg in treated infants, 2.25 kg in control infants. When infants were deemed ready for extubation, dexamethasone 0.5 mg/kg/dose or an equal volume of normal saline was given in three doses 8 hours apart. The final dose was given 1 hour before extubation. Esophageal pressure, air flow integrated to tidal volume (Vt), respiratory rate, and heart rate were measured before extubation, immediately following extubation, and every 20 minutes for 80 minutes. Total pulmonary resistance (RTP), dynamic lung compliance (CL), and minute ventilation (VE) were calculated. Forty-two infants completed the study; 19 infants received dexamethasone and 23 received placebo. There was no difference between the two groups in gestational age, weight at study, or length of intubation. Vt, RTP, VE, and CL were not significantly different between the two groups over time; however, RTP increased over time in the placebo group. Heart rate was significantly lower in the dexamethasone group. We conclude that dexamethasone appears to have limited effect on pulmonary function immediately following extubation in the population studied. Further studies should evaluate the drug effect beginning at least 1 hour after extubation.

Cardiorespiratory effects of changing inspiratory to expiratory ratio during high-frequency oscillation in an animal model of respiratory failure.

To examine the effects of varying inspiratory/expiratory ratio (I/E) on cardiorespiratory function during high-frequency oscillation (HFO), 11 saline-lavaged rabbits were ventilated at I/E = 1:2, 1:1.5, 1.5:1, and 2:1 in a paired comparison to a baseline of I/E = 1:1. HFO was delivered by a SensorMedics model 3100 oscillator at a frequency of 10 Hz. Pressure amplitude and proximal mean airway pressure (PPaw) were held constant as I/E was varied from baseline to the experimental I/E. During each paired observation, PaO2, PaCO2, cardiac output, blood pressure, and distal mean airway pressure (DPaw) were measured. We found that as I/E was increased or decreased from 1:1, no significant changes in PaO2, PaCO2, blood pressure, or cardiac output occurred. We conclude that in this model, varying I/E has no significant effect on oxygenation, ventilation, or cardiovascular function.

Death due to diffuse alveolar hemorrhage in a child with pulmonary veno-occlusive disease.

Pulmonary veno-occlusive disease (PVOD) occurred in a six-year-old girl. Investigation of a number of proposed causes for this uncommon condition and histologic progression of disease are documented. To our knowledge, this is the first case of PVOD in which death was due to massive alveolar hemorrhage.

Measurement of tidal volume using a pneumotachometer during high-frequency oscillation.

To assess the accuracy of a pneumotachometer (PN) for tidal volume (VT) measurements during high-frequency oscillation (HFO), we determined simultaneously VT using a PN and a full body plethysmograph (PL) in 12 rabbits. HFO was delivered with an oscillator at a frequency of 10 Hz, mean airway pressure of 8 cm H2O, and inspiratory time of 50%. Pressure amplitude (delta P) was varied as follows: 40, 60, 80, 20, 100, 40 cm H2O. Finally, in ten rabbits a spacer equal in deadspace (VD) to that of the PN (15 ml) was left in-line for 5 min. Blood gases were obtained before and after the spacer was added. We found that VT-PN correlates well with VT-PL (r = .92), although the difference between VT-PN and VT-PL is greater at large VT. Significant respiratory acidosis developed with the spacer in-line. PN may be used to trend VT during HFO but PN must not be left in-line, as increased VD seriously affects ventilation.

Resource use, efficiency, and outcome prediction in pediatric intensive care of trauma patients.

To study the impact of trauma patients on Pediatric Intensive Care Units (PICUs), 164 trauma patients' data from 1,075 consecutive admissions to five PICUs were reviewed. Resource use (Therapeutic Intervention Scoring System [TISS] points) and mortality risks (Physiologic Stability Index [PSI] and Pediatric Risk of Mortality [PRISM] scores) were obtained daily for all patients. Trauma patients constituted 15.2% of all PICU patients, and used 14.9% of patient care days and 14.5% of TISS points. Efficiency of trauma patient care was 75% overall compared to 79% overall for nontrauma patients (p less than 0.001). Trauma patient mortality was 9.8%. Tests for goodness of fit showed the PSI and PRISM scores to be accurate outcome predictors for trauma patients (PSI: chi 2 (4) = 2.852, p greater than 0.50; PRISM: chi 2 (4) = 1.216, p greater than 0.50). Trauma patients are a minority of PICU patients and deaths. Their resource use is proportional to their numbers, although less efficient than for nontrauma patients. PSI and PRISM are accurate mortality risk predictors for trauma patients.

Cardiopulmonary effects of high frequency positive-pressure ventilation versus jet ventilation in respiratory failure.

Conventional ventilators are frequently used at high rates in the intensive care nursery to achieve adequate oxygenation and ventilation with reduced peak inspiratory pressure. The efficacy and limitations of high frequency positive-pressure ventilation (HFPPV) using a conventional ventilator were studied by comparing the cardiopulmonary effects of HFPPV with those of high frequency jet ventilation (HFJV) in an animal model of respiratory failure. Sixteen saline-lavaged rabbits were ventilated with either HFPPV or HFJV for 2 h using rates of 200 breaths/min, inspiratory to expiratory ratio of 1:2, and FIO2 of 1.0. As controls an additional eight lavaged rabbits were ventilated at conventional rates (40 to 60 breaths/min). Proximal peak inspiratory pressure as indicated on the ventilator manometer or drive pressure was adjusted to maintain acceptable blood gases. Cardiac output (CO) was measured by thermodilution. Although there was a significant decrease in cardiac function over time, there were no significant differences between the groups in CO or stroke volume. Satisfactory oxygenation and ventilation were maintained in all groups. Static respiratory system compliance and mean airway pressure were similar among the groups. Histologic examination of the lungs revealed no differences between the three ventilator groups. The results of this study indicate that both HFPPV and HFJV are effective in short-term maintenance of normal blood gases in respiratory failure without any discernable differences in their effects on cardiovascular function. At very high rates, however, increases in VT are not possible with HFPPV, which limits its usefulness and flexibility in respiratory failure.

Efficiency of intensive care. A comparative analysis of eight pediatric intensive care units.

To calculate overall pediatric intensive care unit (PICU) efficiency rates, 1668 patients representing 6962 patient-days were studied in eight PICUs. The contributions to inefficiency by two patient groups--low-risk monitored patients and potential early-discharge patients--were quantified using measures of daily mortality risk and therapeutic assessments. Low-risk monitored patients never received a unique PICU therapy and had daily mortality risks less than 1%. Potential early-discharge patients were similar to the low-risk monitored patients except that their unnecessary PICU use came only on their last consecutive day(s) of PICU stay. Efficiency ratings ranged from 0.894 to 0.547 in the eight PICUs. Low-risk monitored patients constituted from 16% to 58% of the PICU patient populations and used from 5.4% to 34.5% of the total days of care. Potential early-discharge patients constituted from 12% to 29% of the populations and the potential early-discharge days of care ranged from 5.1% to 17.2% of the total days of care. These results indicate that large disparity exists in efficiency among PICUs. Efficiency rates of greater than 0.80 seem to be a reasonable goal.

Oscillatory cardiopulmonary effects of high-frequency jet ventilation.

The cardiovascular effects of high-frequency jet ventilation (HFJV) were compared with conventional volume ventilation in the anesthetized dog. A unique effect of HFJV on stroke volume and cardiac output was observed when stroke volume was analyzed on a beat-by-beat basis with impedance cardiography. A pronounced amplitude modulation of stroke volume, as well as of pulmonary and arterial pressure, occurred when the frequency of the HFJV approached the heart rate. The beat frequency of these amplitude oscillations was equal to that predicted based upon the frequency of the HFJV and the heart rate. Cardiac outputs obtained by techniques which average several beats will not detect these oscillations in cardiac output. These findings suggest that HFJV can generate an oscillation in thoracic hemodynamics which affects ventricular output in a similar manner.

An evaluation of repeated injections of epinephrine for the initial treatment of acute asthma.

We evaluated 4 treatment regimens using single and multiple injections of epinephrine for the initial treatment of acute asthma in children. Twenty-five patients received 2 injections of epinephrine followed by Sus-Phrine (Group EES) given 20 min apart, 25 received Sus-Phrine only (Group S), 24 received Sus-Phrine followed by 2 placebo injections 20 min apart (Group SPP), and 14 received epinephrine only (Group E). Clinical score and pulmonary function were assessed over a 2-h period. The failure rate was similar in Groups EES, S, and SPP (combined failure rate, 17.8%). The failure rate (46%) in Group E was significantly greater (p less than 0.05). The clinical score and pulmonary function was significantly better 5 min after the first injection in Group EES than in Groups S and SPP, but no significant differences were noted thereafter. At 25 min the pulmonary function was similar whether 1 or 2 epinephrine injections were administered. The number of patients exhibiting side effects was significantly greater in the groups receiving epinephrine than in the groups receiving Sus-Phrine only (p less than 0.05). The relapse rates during the 24-h period after the emergency room treatment were similar in Groups EES, S, and SPP (combined relapse rate, 14.3%). We conclude that repeated injections of epinephrine are necessary to sustain bronchodilation but that they do not have a cumulative effect. Furthermore, there is little therapeutic advantage of these repeated injections over a single injection of Sus-Phrine for the initial treatment of acute asthma.

Hypnosis for exercise-induced asthma.

Hypnosis has been used for many years in the treatment of asthma, but studies of its usefulness have been controversial. We assessed the efficacy of hypnosis in attenuating exercise-induced asthma (EIA) in 10 stable asthmatics. The subjects ran on a treadmill while mouth breathing for 6 min on 5 different days. Pulmonary mechanics were measured before and after each challenge. Two control exercise challenges resulted in a reproducible decrease in forced expiratory volume in one second (FEV1). On 2 other days, saline or cromolyn by nebulization was given in a double-blind manner with the suggestion that these agents would prevent EIA. Hypnosis prior to exercise resulted in a 15.9% decrease in FEV1 compared with a 31.8% decrease on the control days (p less than 0.001). Pretreatment with cromolyn resulted in a 7.6% decrease in FEV1. We conclude that hypnosis can alter the magnitude of a pathophysiologic process, namely, the bronchospasm after exercise in patients with asthma.