Comparison of neurons in rat medulla oblongata with fos immunoreactivity evoked by seizures, chemoreceptor, or baroreceptor stimulation.

Neurons in rat medulla oblongata with Fos immunoreactivity as a marker of synaptic excitation evoked by pentylenetetrazole-induced seizures were compared with cell populations activated by the stimulation of chemoreceptor and baroreceptor afferent pathways. Chemoreceptors were stimulated by placing rats in a hypoxic gas mixture (7% oxygen) for 2 h. Baroreceptors were activated by phenylephrine-induced hypertension. Seizures and hypoxia induced Fos immunoreactivity in neurons with similar anatomical distributions in the nucleus tractus solitarius, dorsal motor nucleus of the vagus, and ventrolateral medulla. Hypertension was associated with Fos immunoreactivity in an overlapping anatomical distribution compared to seizures and hypoxia, but in a more restricted pattern. A similar proportion of catecholaminergic cells of medulla oblongata (cells immunoreactive for catecholamine synthetic enzymes, tyrosine hydroxylase or phenylethanolamine-N-methyltransferase) had Fos immunostaining after seizures and hypoxia (P > 0.05), while significantly fewer were activated by hypertension (P < 0.05). The majority of tyrosine hydroxylase-immunoreactive cells in caudal ventrolateral medulla were activated by both seizures and hypoxia (mean per cents, 79 and 67%, respectively). Since cell populations activated by seizures and hypoxia are indistinguishable, and a majority of tyrosine hydroxylase-reactive cells in caudal ventrolateral medulla are independently activated by each stimulus, it may be inferred that some impulses originating from seizures and chemoreceptor afferent pathways converge to a common set of neurons. These observations identify neurons in rat medulla oblongata which may mediate the impact of seizures on central processing of chemoreceptor afferent activity.

Adverse events during interhospital transport: physiologic deterioration associated with pretransport severity of illness.

The relationship between severity of illness or injury before interhospital transport and the incidence of physiologic deterioration during transport was studied in 117 pediatric patients. Transports were done by referring hospital personnel. Pretransport severity was expressed as the Pediatric Risk of Mortality score for all patients and as the Modified Injury Severity Score for trauma patients. For 71 patients with Pediatric Risk of Mortality scores less than 10, deterioration during transport occurred in 3 (4%) and hospital mortality occurred in 2 (3%). For 10 victims of trauma with Modified Injury Severity Scores less than 10, none had deterioration during transport or hospital mortality. The rare occurrence of serious problems related to transport in low-risk patients indicates that referring hospital personnel are capable of safely transporting such patients. The incidence of physiologic deterioration during transport was significantly greater (P less than .01) with greater pretransport severity of illness or injury. Failure to intubate the trachea was not a major preventable cause of deterioration. The most common preventable problem occurred for 6 of 79 patients with endotracheal tubes that became occluded with secretions, leading to cyanosis in 2 patients. Our data concerning high-risk patients with specified pretransport severity provide a basis for comparison for further evaluation of the benefit of specialized pediatric transport services.

Central venous catheter insertion by femoral vein: safety and effectiveness for the pediatric patient.

Prospective observations made during surveillance of routine central venous catheterizations for hemodynamic monitoring were evaluated to determine the safety and effectiveness of femoral insertion of central venous catheters and to demonstrate the feasibility of teaching pediatric residents to perform this procedure. During a 19-month period of observation, 29 pediatric patients requiring a central venous catheter underwent attempted percutaneous femoral vein catheterization. Femoral catheterization was successful in 86% of patients attempted, and insertions by pediatric residents were successful in 68% of patients attempted. Arterial puncture was the only significant complication of insertion, occurring in 14%, and was not associated with adverse sequelae. During 33 months of observations, complications of indwelling femoral central venous catheters did not significantly exceed the frequency for internal and external jugular, subclavian, and antecubital central venous catheters. During more than 4 years of observation, the significant complications associated with indwelling femoral central venous catheters were swelling of the leg or documented thrombosis in 11% of 74 critically ill patients. These observations indicate safety and effectiveness of femoral central venous catheters which compares favorably to central venous catheter insertion by other routes. In contrast to previous reports of central venous catheter insertion via subclavian and internal jugular veins, we observed no cardiorespiratory compromise as a result of femoral central venous catheter complications. Skill in this technique is a feasible educational goal for pediatric residents.

Excess morbidity associated with interhospital transport.

A prospective study was performed to determine whether excess morbidity occurred in critically ill and injured pediatric patients during interhospital transport compared with morbidity in a control group. Control observations were made during the first 2 hours of pediatric intensive care unit (PICU) care of patients emergently admitted from within the same institution and not requiring interhospital transport. The first 2 PICU hours of control patients corresponded to the interval of transport in those who required interhospital transfer. Transport care was provided by nonspecialized teams from referring hospitals. Morbidity occurred in 20.9% of 177 transported patients, exceeding the morbidity rate of 11.3% in 195 control patients (P < .05). The difference in morbidity was due to intensive care-related adverse events (eg, plugged or dislodged endotracheal tubes, loss of intravenous access) in 15.3% and 3.6% of transported and control patients, respectively (P < .05). Physiologic deterioration occurred at similar rates of 7.9% and 8.7% in transported and control patients, respectively (P > .05). Slightly greater pre-ICU severity of illness in transported than control patients (median Pediatric Risk of Mortality Score = 10 and 7, respectively, P < .05) and greater pre-ICU therapy relative to severity (P < .05) in control patients are potential confounding sources of the morbidity differences. If patients are stratified into subgroups of similar pre-ICU severity, an excess of intensive care-related adverse events in transported patients remains evident in the severe subgroup (P < .05). Further investigation is warranted to determine whether specialized transport teams can reduce the excess morbidity associated with interhospital transport of critically ill and injured pediatric patients.

Anatomy of femoral vessels in infants and guidelines for venous catheterization.

This study was performed to formulate femoral venous catheterization guidelines for infants from ultrasound observations. Femoral vessels were evaluated on both sides in 75 infants, 2 weeks to 24 months of age. The site of the greatest probability of successful venipuncture 1 cm below the skin crease at the groin is located 4 to 5 mm medial to the femoral artery pulse. If it is assumed that entry into the central half of the vein will result in successful catheterization, successive attempts 5 mm and 6 mm medial to the pulse would result in cumulative successful insertion in 53% and 61%, respectively, with no arterial punctures. A third attempt 4 mm medial to the pulse further increases cumulative success to 78%, but 3% arterial punctures would occur. These guidelines are intended to facilitate achievement of femoral venous catheterization, minimizing arterial punctures and number of needle passes required.

Seizure-induced c-fos expression in rat medulla oblongata is not dependent on associated elevation of blood pressure.

This study was performed to determine whether c-fos immunoreactivity (IR) induced in medulla oblongata by pentylenetetrazole seizures is a consequence of seizure-associated blood pressure elevation and activation of baroreceptor afferent pathways, or occurs independently of hypertension. Immunohistochemical study of sections of medulla oblongata revealed that seizures are followed by induction of c-fos IR in nucleus tractus solitarius (NTS), dorsal motor nucleus of the vagus (DMN 10), and ventrolateral medulla (VLM), while there is negligible c-fos IR after saline sham injections. Seizures were associated with blood pressure elevation peaking at 31 +/- 17% (+/- SD) above baseline. Experimental hypertension at a similar level induced by i.p. phenylephrine also resulted in induction of c-fos IR in NTS. When seizures were preceded by antihypertensive treatment with the alpha-adrenergic antagonist, phentolamine, peak blood pressure tended to remain near the baseline level and lower than sham-injected controls. Normotensive seizures were associated with c-fos IR in NTS, DMN 10, and VLM similar to the pattern following hypertensive seizures. Seizure-induced activation of c-fos IR occurred despite normal blood pressure, and thus can be attributed to a direct effect of the seizure, and not to an indirect effect mediated by hypertension.

Evaluation and stabilization of the critically ill child.

Because the timely treatment of children in accidents or with serious illnesses usually is successful, it is vital that the life-threatening problem promptly be recognized. Although the principles of resuscitation are identical in the child and adult, age-related differences in anatomy and pathophysiology may make this task challenging for the physician who usually cares for adults. In this article, a systematic approach to evaluation and initial stabilization of the pediatric patient is discussed. Decisions and methods in safely transferring a critically ill pediatric patient are also reviewed.

Duration of intracranial pressure monitoring does not predict daily risk of infectious complications.

A group of 205 patients (115 children and 90 adults) with a total of 212 intracranial pressure (ICP) monitors were retrospectively studied with attention to daily cerebrospinal fluid cultures, duration of monitoring, associated cranial injuries, and hospital site of the ICP monitor (intensive care unit or operating room). Only closed ICP monitoring systems without irrigation or compliance testing were used, and all patients received antibiotics as prophylaxis throughout the monitoring period. There were no complications associated with monitor placement. Incidence histograms and regression analysis were used to determine the daily risk of subsequent infections, in addition to evaluating the cumulative risk of infection, as has been previously described in the literature. No relation between the duration of ICP monitoring and the rate of daily infection through the period of maximal monitoring (1-2 weeks) was found in this series. The overall incidence of infection was 7.1% with a median duration of monitoring of 7.2 days. The age of the patient (adult vs. child), site of ICP monitor placement, and nature of the underlying disease (trauma vs. nontrauma) had no significant effect on the development of monitor-related infections in our study. These data indicate that the decision to continue ICP monitoring can be based solely on the clinical necessity for further monitoring rather than on concerns for monitor removal to prevent infection.

A model for evaluation of gas exchange: mouth to mouth ventilation of infants by emergency medical technicians.

We describe a model for evaluating techniques of infant ventilation during resuscitation. The utility of the model is illustrated by testing performance of emergency medical technicians in mouth to mouth ventilation of a model 4 kg infant. Ventilation was generally adequate with mean (+/- S.D.) frequency 22 +/- 9 breaths per minute and tidal volume 40 +/- 13 ml. Gas delivered to the model consisted of PICO2 7 +/- 6 mmHg and FIO2 0.20 +/- 0.007. Assuming normal metabolic rate and respiratory dead space, alveolar gas composition resulting from the simulated resuscitations would be PACO2 = 31 +/- 20 and PAO2 = 110 +/- 19 mmHg. Nine of ten rescuers would have achieved satisfactory PACO2 less than or equal to 50 and PAO2 greater than or equal to 100. However, the rescuers' exhaled oxygen concentration is not adequate to correct hypoxemia if associated with hypoventilation or a wide alveolar to arterial oxygen gradient.

The influence of diazepam or lorazepam on the frequency of endotracheal intubation in childhood status epilepticus.

Anticonvulsant management of status epilepticus (SE) may result in respiratory depression, often requiring endotracheal intubation (ETI). By examining rates of ETI in childhood SE after intravenous diazepam or lorazepam, when administered alone or in combination with phenytoin, the influence of anticonvulsants on the frequency of ETI during SE was determined. The medical records of 142 consecutive children younger than 16 years of age admitted from a university hospital ED with seizures during a 28-month period were retrospectively reviewed. SE was identified in 38 (27%) of cases. Records of children with SE were reviewed for demographic, seizure severity, and management variables. Twelve patients were excluded, ten of whom received concomitant phenobarbital. Patients receiving lorazepam had ETI rate of 27% (4/15), compared to 73% (8/11) in the diazepam group (P = 0.026, Fisher's exact). The groups were not significantly different in age, weight, sex, seizure type, seizure duration, and appropriate anticonvulsant dosage. A prospective, randomized trial comparing lorazepam and diazepam is warranted to confirm the apparent advantage of lorazepam in reducing respiratory depression.

Association of arterial hypertension with poor outcome in children with acute brain injury.

We studied intensive care unit (ICU) records of 42 comatose children with acute brain injuries to define the relationship between high arterial blood pressure and poor neurologic recovery. Diagnoses included head trauma, anoxia, Reye's syndrome, and central nervous system infection. The highest systolic blood pressure in all 42 patients exceeded the 95th percentile. In those whose highest systolic pressure exceeded 95th percentile by more than 20 torr, severe neurologic deficit or death occurred in 19 of 34 (56%), while in those with milder hypertension, poor outcome occurred in only one of eight (13%, p = 0.0316). Of those with high blood pressure persisting until ICU discharge, 14 of 19 (74%) had poor outcome, while those with blood pressure normalizing prior to ICU discharge had poor outcome in only six of 23 (26%, p = 0.0026). High blood pressure was not usually a reflex effect of elevated intracranial pressure. This finding suggests that measures to control high blood pressure are indicated in the management of the acutely brain-damaged child.

Effect of RSV bronchiolitis practice guidelines on resource utilization.

We sought to determine whether institution of respiratory syncytial virus (RSV) practice guidelines decreased resource utilization for a heterogeneous population of children hospitalized with RSV bronchiolitis. Patients less than 24 months old with RSV bronchiolitis at a pediatric referral center were identified by retrospective chart review for consecutive RSV seasons. Before the guidelines were instituted patients were less likely to have a documented physician's assessment of response to albuterol, were more likely to have received supplemental oxygen and cardiorespiratory monitoring, and to be discharged on an albuterol regimen. Patients received more albuterol treatments. After the guidelines were in place fewer resources were utilized in the care of patients with RSV bronchiolitis. RSV practice guidelines may simplify and streamline the care of a heterogeneous population of children with bronchiolitis.

Evaluation of mask-bag ventilation in resuscitation of infants.

Performance of mask-bag ventilation was evaluated on an infant resuscitation mannequin to resolve uncertainty regarding the proficiency of pediatric resuscitation personnel in this technique and to determine whether the type of resuscitation bag used would affect performance. Performance using a self-inflatable resuscitation bag was generally adequate. Forty-six of 50 operators achieved an adequate minute ventilation, and 48 of 50 operators achieved a mean tidal volume exceeding that of the mask plus simulated physiologic dead space. Wide variation with a tendency to hyperventilate and to use excessive pressures indicate the need for improved standard training methods. Technical difficulties with an anesthesia bag impaired performance, suggesting that only self-inflatable bags should be used for mask-bag ventilation during pediatric resuscitation, unless the staff's proficiency with anesthesia bags is clearly demonstrated.

Post-intensive care unit pediatric hospital stay and estimated costs.

OBJECTIVE: For pediatric intensive care unit (ICU) survivors, to determine the proportion of hospital stay and estimated hospital costs accounted for by post-ICU care. DESIGN: Prospective study. SETTING: University teaching hospital. PATIENTS: Pediatric patients who survive an ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Estimated relative daily costs were assumed as follows: ICU, with ventilator/ICU, not on ventilator/intermediate care unit/general pediatric hospital day, at 2:1:0.7:0.3, respectively. Estimated costs were expressed in arbitrary units as (number of days at each level of care) x (relative cost per day). The ICU phase was defined as the patient's first ICU admission only, and the post-ICU phase included intermediate care unit and general pediatric hospital days, as well as ICU readmission during the same hospitalization. Pre-ICU hospital activity was excluded from analysis. For 341 ICU survivors, post-ICU days (median, 4 days per patient) accounted for 62% of the total hospital stay. Post-ICU care accounted for one third of the total estimated hospital costs for ICU survivors. Patients with longer post-ICU stays could not be reliably identified at the time of ICU discharge according to their ICU length of stay, duration of mechanical ventilation in the ICU, age, ICU day 1 mortality probability, or diagnostic group (p>.05). CONCLUSIONS: Post-ICU care accounts for a substantial proportion of hospital stay and estimated costs for ICU survivors. These observations suggest that developing strategies to optimize hospital utilization at the time of ICU discharge may be important for controlling costs of recovery from critical illness.

Central contribution to hypoventilation during severe inspiratory resistive loads.

OBJECTIVE: Recent observations suggest that central hypoventilation with slowing of respiratory frequency contributes to hypoventilation during severe inspiratory resistive loads. We carried out a study to further characterize this bradypneic response. DESIGN: Prospective, controlled laboratory study. SETTING: Basic science laboratory of a university hospital. SUBJECTS: Anesthetized adult cats (loading experiment n = 7, nonloaded hypercapnic controls n = 11). INTERVENTIONS: Experimental inspiratory loads increased transdiaphragmatic pressure to 75% of the maximum for each animal. Respiratory responses were observed at midrun or moderate conditions of respiratory insufficiency (defined as PaCO2 > or = 60 torr [> or = 8.0 kPa]) and failure (PaCO2 > or = 80 torr [> or = 10.6 kPa]). Nonloaded hypercapnic controls were studied with similar durations of exposure to CO2 in the same CO2 range. MEASUREMENTS: Inspiratory airflow, tidal volume, respiratory frequency, airway pressure, transdiaphragmatic pressure, transdiaphragmatic pressure response to phrenic nerve electrical stimulation, blood gas analysis. Severe inspiratory loads were applied to anesthetized adult cats to determine whether bradypnea could be observed in an anesthesized model that eliminated conscious responses. Experiments were performed in hyperoxic conditions to determine whether bradypnea develops in the absence of hypoxia. An additional control group was studied under hypercapnic conditions without loading to determine whether comparable hypercapnia is a sufficient stimulus to elicit bradypnea. RESULTS: From midrun until failure, minute ventilation decreased by 16% in loaded animals. Hypoventilation was associated with a decrease in respiratory frequency from 40.1 to 29.9 breaths/min, whereas tidal volume, spontaneous transdiaphragmatic pressure, and transdiaphragmatic pressure response to phrenic nerve electrical stimulation remained unchanged. Control animals had no significant reduction in ventilation or respiratory frequency over similar levels and durations of hypercapnia. CONCLUSIONS: Centrally mediated bradypnea contributed to hypoventilation in respiratory failure associated with inspiratory loading. Bradypnea preceded evidence of muscle fatigue. This change in respiratory cycle timing occurred under anesthesia, and thus, did not depend on conscious perception of dyspnea. Bradypnea does not depend on either hypercapnia or hypoxia.

Arterial-end tidal PCO2 equilibration in the cat during acute hypercapnia.

We have studied the problem of pulmonary capillary-alveolar CO2 exchange in the cat during acute hypercapnia. Three cats, anesthetized with xylazine and pentobarbital sodium and prepared with acute tracheostomy and femoral arterial catheter, and three awake cats, prepared with a small tracheal catheter and femoral arterial catheter, were subjected to acute hypercapnia (FICO2 = 0.00, 0.06, and 0.08). During steady states, end tidal PCO2 was determined with an infrared analyzer, and arterial PCO2 was measured with a Radiometer ABL-2 analyzer in simultaneously drawn samples. In vitro studies indicated that our blood sampling techniques resulted in a 6% reduction in PCO2. Blood PCO2 readings were corrected for (1) non-ideal performance of the analyzer as determined by tonometry, (2) 6% reduction due to sampling, and (3) differences between electrode and rectal temperature. Mean arterial-end tidal PCO2 differences were not significantly different from zero in any condition in either group (except for 0.08 CO2 in the awake group when the difference was 2.0 Torr). These findings in the cat agree with the classical view that PCO2 in pulmonary capillary blood approaches PCO2 in alveolar gas. Further, our findings provide evidence that CO2 loss from blood samples is an important technical factor which can cause systematic underestimation of blood PCO2 and, hence, contribute to the observation of negative PCO2 gradients.

Early pneumococcal sepsis after pulmonary aspiration and the adult respiratory distress syndrome.

Bacterial pneumonia often complicates recovery several days after aspiration of gastric and oropharyngeal contents. Two children aspirated vomitus resulting in adult respiratory distress syndrome (ARDS) and suffered life-threatening pneumonia and septicemia caused by Streptococcus pneumoniae on the 2nd day after aspiration. We presume that inoculation of oropharyngeal bacteria into severely injured lung resulted in unusually rapid progression of infection. A high index of suspicion is necessary to detect this early complication because clinical signs of infection were obscured by ARDS.

Pulmonary edema associated with upper airway obstruction.

We retrospectively surveyed records of 153 patients with croup or epiglottitis. Thirty-four children required intubation of the trachea to relieve upper airway obstruction. In those requiring intubation, pulmonary edema occurred in four (12%) of 34. Review of 17 previously reported cases, along with our patients, demonstrated that onset of pulmonary edema due to upper airway obstruction usually follows intubation. A PaO2 below 50 mm Hg is observed in 38% and pneumothorax in 24% of all reported cases. Supplemental oxygen, positive end-expiratory pressure, mechanical ventilation, and chest tube drainage have prevented death despite these life-threatening complications.