Lorry R. Frankel

A controlled trial of aerosolized ribavirin in infants receiving mechanical ventilation for severe respiratory syncytial virus infection.

BACKGROUND Although the antiviral agent ribavirin improves the course of lower respiratory tract disease in spontaneously breathing infants with respiratory syncytial virus infection, it is not known whether ribavirin can benefit infants with severe respiratory syncytial virus disease who require mechanical ventilation. METHODS We conducted a randomized, double-blind, placebo-controlled evaluation of ribavirin (20 mg per milliliter) administered continuously in aerosolized form to infants receiving mechanical ventilation for respiratory failure that was caused by documented respiratory syncytial virus infection. RESULTS Of the 28 infants (mean [+/- SD] age, 1.4 +/- 1.7 months) enrolled, 7 had underlying diseases predisposing them to severe infection (mean age, 3.0 +/- 2.6 months), and 21 were previously normal (mean age, 0.8 +/- 0.9 month). Among the 14 infants who received ribavirin, the mean duration of mechanical ventilation was 4.9 days (as compared with 9.9 days among the 14 who received placebo; P = 0.01), and the mean length of supplemental oxygen use was 8.7 days (as compared with 13.5 days; P = 0.01). The mean length of the hospital stay was 13.3 days after treatment with ribavirin and 15.0 with placebo (P = 0.04). When only the 21 previously normal infants were considered, the mean length of the hospital stay was 9.0 days for the ribavirin recipients and 15.3 days for those who received placebo (P = 0.005). CONCLUSIONS In infants who require mechanical ventilation because of severe respiratory syncytial virus infection, treatment with aerosolized ribavirin decreases the duration of mechanical ventilation, oxygen treatment, and the hospital stay.

Clinical practice guidelines for the maintenance of patient physical safety in the intensive care unit: Use of restraining therapies— American College of Critical Care Medicine Task Force 2001-2002

ObjectiveTo develop clinical practice guidelines for the use of restraining therapies to maintain physical and psychological safety of adult and pediatric patients in the intensive care unit. ParticipantsA multidisciplinary, multispecialty task force of experts in critical care practice was convened from the membership of the American College of Critical Care Medicine (ACCM), the Society of Critical Care Medicine (SCCM), and the American Association of Critical Care Nurses (AACN). EvidenceThe task force members reviewed the published literature (MEDLINE articles, textbooks, etc.) and provided expert opinion from which consensus was derived. Relevant published articles were reviewed individually for validity using the Cochrane methodology (http://hiru.mcmaster.ca/cochrane/ or www.cochrane.org). Consensus ProcessThe task force met as a group and by teleconference to identify the pertinent literature and derive consensus recommendations. Consideration was given to both the weight of scientific information within the literature and expert opinion. Draft documents were composed by a task force steering committee and debated by the task force members until consensus was reached by nominal group process. The task force draft then was reviewed, assessed, and edited by the Board of Regents of the ACCM. After steering committee approval, the draft document was reviewed and approved by the SCCM Council. ConclusionsThe task force developed nine recommendations with regard to the use of physical restraints and pharmacologic therapies to maintain patient safety in the intensive care unit.

Retinal Folds in the Shaken Baby Syndrome

We examined two children with presumed shaken baby syndrome. Both children suffered severe, indirect closed head trauma with intracranial hemorrhage, sharply increased intracranial pressure, and extensive neurologic damage. In addition to extensive retinal and preretinal hemorrhages, bilateral symmetric white ring-shaped retinal folds were seen encircling the macula outside the vascular arcades. These retinal folds may be a hallmark of shaking injuries in child abuse victims.

Identification of Epstein-Barr virus-specific CD8+ T lymphocytes in the circulation of pediatric transplant recipients.

Background. Pediatric transplant recipients are at increased risk for Epstein Barr virus (EBV)-related B cell lymphomas. In healthy individuals, the expansion of EBV-infected B cells is controlled by CD8+ cytotoxic T cells. However, immunosuppressive therapy may compromise antiviral immunity. We identified and determined the frequency of EBV-specific T cells in the peripheral blood of pediatric transplant recipients. Methods. HLA-B*0801 and HLA-A*0201 tetramers folded with immunodominant EBV peptides were used to detect EBV-specific CD8+ T cells by flow cytometry in peripheral blood mononuclear cells from 24 pediatric liver and kidney transplant recipients. The expression of CD38 and CD45RO on EBV-specific, tetramer-binding cells was also examined in a subset of patients by immunofluorescent staining and flow cytometry. Results. Tetramer-binding CD8+ T cells were identified in 21 of 24 transplant recipients. EBV-specific CD8+ T cells were detected as early as 4 weeks after transplant in EBV seronegative patients receiving an organ from an EBV seropositive donor. The frequencies (expressed as a percentage of the CD8+ T cells) of the tetramer-binding cells were HLA-B8-RAKFKQLL (BZLF1 lytic antigen peptide) tetramer, range=0.96 to 3.94%; HLA-B8-FLRGRAYGL (EBNA3A latent antigen peptide) tetramer, range=0.03 to 0.59%; and HLA-A2-GLCTLVAML (BMLF1 lytic antigen peptide) tetramer, range=0.06 to 0.76%. The majority of tetramer reactive cells displayed an activated/memory phenotype. Conclusions. Pediatric transplant recipients receiving immunosuppression can generate EBV-specific CD8+ T cells. Phenotypic and functional analysis of tetramer+ cells may prove useful in defining and monitoring EBV infection in the posttransplant patient.

Group A streptococcal meningitis: report of a case and review of literature since 1976.

Group A streptococcal (GAS) invasive disease has become increasingly common in recent years. However, acute bacterial meningitis caused by this pathogen is unusual. We report a case of GAS meningitis in a previously healthy 21/2-year-old child associated with a dramatically rapid course and fatal outcome. A literature review of previously reported cases is presented. This case serves as a reminder that GAS can cause severe meningitis in otherwise healthy hosts.

Use of the anterior cricoid split operation in infants with acquired subglottic stenosis.

Ten infants with acquired subglottic stenosis were treated successfully using the anterior cricoid split operation. Eight had been preterm infants who required endotracheal intubation and assisted ventilation for the respiratory distress syndrome. Two had been born at term; 1 required mechanical ventilation for aspiration of meconium and the other intubation for obstructive apnea. All had been extubated successfully in less than 2 wk and were discharged home with no signs of subglottic stenosis. These infants were referred at 2 to 13 months of age for evaluation of upper airway obstruction. By bronchoscopy, we confirmed severe subglottic stenosis in each of the infants. The anterior cricoid split procedure requires a single midline vertical incision through the anterior cartilaginous ring of the cricoid cartilage and the upper 2 tracheal rings. Our postoperative management included 7 to 10 days of endotracheal intubation, mechanical ventilation, neuromuscular blockade, sedation, and total parenteral nutrition. All were extubated at the end of this period without evidence of stridor or obstructive apnea. One patient developed a subglottic granuloma at the level of the cricoid cartilage 4 months after the operation; this was successfully excised with the carbon dioxide laser. The other 9 patients remain asymptomatic 1 month to 1 yr after the surgical repair.

Hepatic failure following ingestion of multiple doses of acetaminophen in a young child.

A 7-month-old male developed hepatic failure following the mistaken administration of multiple excessive doses of acetaminophen. Hepatic toxicity following multiple dose ingestion has been reported infrequently. Risk factors for hepatic toxicity following multiple dose ingestion are discussed.

A technique for the administration of ribavirin to mechanically ventilated infants with severe respiratory syncytial virus infection

Fifteen infants with respiratory syncytial virus pulmonary infection admitted to our pediatric ICU from December 1, 1985 through April 30, 1986, required mechanical ventilation. These patients were placed on an open trial of ribavirin therapy. We describe a technique for the safe delivery of aerosolized ribavirin to these infants while on the ventilator. The agent was delivered for 16 h/day for 7 days. Modifications of the ventilator circuit were needed to prevent the condensation of the drug in the ventilator tubing and to allow for the safe and effective operation of the ventilator. A common ventilator strategy was used for all patients. The highest positive inspiratory pressure generated was 42 +/- 9.5 (SD) cm H2O, the highest PEEP was 5.9 +/- 3.2 cm H2O, the duration of ventilation was 10.7 +/- 8.5 days, and exposure to fraction of inspired oxygen was greater than or equal to 0.6 for 55.3 h. Ribavirin levels were measurable in two patients, thereby demonstrating that the drug was in fact delivered and absorbed. Our preliminary results demonstrate that ribavirin can be delivered to the patients with respiratory syncytial viral infections who require mechanical ventilation; however, further studies are indicated to evaluate the efficacy and dose responsiveness, alterations in pulmonary dynamics, and safety of ribavirin in delivery to infants requiring ventilation.

Severe metabolic acidosis after acute naproxen sodium ingestion

Naproxen, a nonsteroidal anti-inflammatory drug (NSAID), is a propionic acid derivative that possesses analgesic and antipyretic properties through inhibition of prostaglandin synthesis. The propionic acids have been considered the least toxic of the NSAIDs, and one, ibuprofen, is currently available as an over-the-counter medication. Though acidosis has been reported with ibuprofen, no such occurrence has been reported for naproxen sodium. We report the case of a 15-year-old girl who presented with severe metabolic acidosis and seizures that rapidly followed naproxen sodium ingestion. Serum bicarbonate levels returned to normal 12 hours after admission and correlated with the known pharmacokinetics of naproxen. The pharmacokinetics of naproxen and treatment of its overdose, and possible mechanisms of metabolic acidosis are reviewed.

Dissociation of mean airway pressure and lung volume during high-frequency oscillatory ventilation.

Eight kittens were studied during high-frequency oscillatory ventilation (HFOV) using an airway vibrator. HFOV was performed at 1000 and 1800 cycle/min at three present oscillatory amplitude settings and with lungs normal and injured by saline lavage. Change in lung volume (LV) during HFOV was compared to change in LV obtained during static inflation at matched mean airway pressure (Paw) of 5, 10, 15 and 20 cm H2O. LV during HFOV was significantly higher than during static inflation, and increased as oscillatory amplitude increased. LV was significantly lower after lung injury for matched HFOV settings, and was not affected by rate. Dissociation of Paw and LV during HFOV is observed implying that mean alveolar pressure (Palv) exceeds Paw during HFOV in this experimental model. The safe clinical application of HFOV may involve measurement of Palv or LV.