Intracatheter nitroglycerin infusion fails to prevent catheter-related venous thrombosis: a randomized, controlled trial.

OBJECTIVE: Catheter-related thrombosis is a common problem in the pediatric intensive care unit. Strategies that reduce the incidence of thrombosis may have significant clinical advantage. Nitroglycerin (NTG) infusions release nitric oxide (NO). NO is responsible for much of the vasodilating and antithrombotic properties of the vasculature. We hypothesized that an intracatheter NTG infusion would reduce the incidence of catheter-related thrombosis. DESIGN: Prospective, randomized, controlled trial. SETTING: Pediatric intensive care unit. PATIENTS AND PARTICIPANTS: Children of 6 years or less with femoral venous catheters who were not on antithrombotic therapy. INTERVENTIONS: Subjects were randomly assigned to NTG or control groups. NTG group patients received NTG at 0.1 mcg x kg x min in 5 % dextrose; control group patients received only 5 % dextrose. Infusions were delivered continuously through the catheter until the catheter was removed. Demographic data, physical and laboratory findings, catheter insertion attempts and infusate composition were recorded. Clinical evidence of vascular thrombosis or catheter malfunction was noted. Ultrasound examinations were performed within 2 days of catheter insertion and within 2 days after removal. MEASUREMENTS AND RESULTS: Forty-four patients (age 12.0 +/- 2.6 months) completed the study, 21 in the NTG group and 23 in the control group. Duration of catheter placement was 7.5 +/- 0.7 days. Twelve of 44 patients (27 %) had thrombi: 7/21 in the NTG group; 5/23 in the control group (p = NS). There were no significant differences between children with and without thrombi in age, gender, number of insertion attempts, duration of catheter placement, clinical signs of thrombosis or infections. CONCLUSIONS: Catheter-related thrombosis is common after placement of femoral venous catheters in children. Low dose intracatheter NTG infusion does not protect against catheter-related venous thrombosis in children.

Postoperative management of children after single-stage laryngotracheal reconstruction.

OBJECTIVE: To report the safety and efficacy of a postoperative approach that avoids pharmacologic and physical restraints and allows liberal physical activity after single-stage laryngotracheal reconstruction in children. DESIGN: Retrospective study. SETTING: Tertiary care pediatric intensive care unit. PATIENTS: One hundred thirty-three children who underwent single-stage laryngotracheal reconstruction, including laryngotracheoplasty, tracheal resection, and cricotracheal resection. INTERVENTIONS: Five-year period of data collection regarding postoperative care and complications. MEASUREMENTS AND MAIN RESULTS: The medical records of all patients (age range, 2-336 months; mean age +/- SEM, 66 +/- 5 months) who underwent single-stage laryngotracheoplasty, tracheal resection, or cricotracheal resection between 1993 and 1998 were reviewed. Tracheally intubated, awake, and unrestrained patients (group 1, n = 54; mean age, 113 +/- 8 months) were compared with tracheally intubated, sedated, and restrained patients (group 2, n = 79; mean age, 33 +/- 3 months). Pediatric intensive care unit length of stay was less in group 1 in comparison with group 2 patients (11.2 +/- 0.5 days vs. 13.7 +/- 0.6 days; p = .007). Hospital length of stay was less in group 1 than group 2 patients (16.7 +/- 1.0 days vs. 21.1 +/- 1.1 days; p = .01). Adverse events were fewer in group 1 compared with group 2 patients: atelectasis, 44% vs. 73% (p < .001); postextubation stridor, 22% vs. 53% (p < .001); and withdrawal syndromes, 0% vs. 43% (p < .001). The occurrence of pneumonia, airleak syndromes, unplanned extubation, and aspiration events was not different between groups. CONCLUSIONS: For developmentally appropriate children, postoperative management after single-stage laryngotracheal reconstruction does not require the use of physical and pharmacologic restraints. Older children who are not sedated or restrained and who are allowed liberal physical activity have shorter pediatric intensive care unit and hospital lengths of stay, and a decreased incidence of postoperative adverse events. Centers performing single-stage laryngotracheal reconstruction should consider a postoperative management strategy that avoids sedatives, muscle relaxants, and physical restraints, and allows liberal bedside physical activity in developmentally appropriate children.

Soluble nitric oxide donor and surfactant improve oxygenation and pulmonary hypertension in porcine lung injury.

Acute lung injury (ALI) is associated with diminished surfactant activity and pulmonary hypertension. NONOates are soluble NO donors which release NO in solution. Intratracheal NONOates reduce pulmonary hypertension and improve oxygenation in ALI. We hypothesized that the pharmacologic properties of NO donors would be unaltered after surfactant admixture in vitro and that aerosolized NONOate activity would be enhanced by surfactant pretreatment in vivo. NO donors were added to saline or surfactant and analyzed for nitrite/nitrate production and aortic ring vasodilation. Surfactant did not alter nitrate/nitrite production or aortic ring vasodilation. A porcine model of ALI with pulmonary hypertension was produced using intravenous oleic acid. Animals were assigned to Surfactant-Saline, Surfactant-NONOate, Saline-Saline, or Saline-NONOate groups. Saline or surfactant was instilled into the trachea, followed by gas exchange, pulmonary function, and hemodynamic measurements. NONOate or saline was then aerosolized, and additional data were collected. Oxygenation was improved in the Surfactant-NONOate group, while pulmonary hypertension was selectively reduced in both NONOate groups. Aerosolized NONOate following surfactant pretreatment improves oxygenation and reduces pulmonary hypertension in ALI.

Aerosolized soluble nitric oxide donor improves oxygenation and pulmonary hypertension in acute lung injury.

Acute respiratory distress syndrome (ARDS) is a major cause of morbidity and mortality in critically ill patients. The associated ventilation/perfusion mismatch and pulmonary hypertension are amenable to treatment with inhaled nitric oxide (NO) gas. Compounds formed by reacting NO with various nucleophiles (NONOates) release NO spontaneously and induce vasodilation. Intratracheally administered NONOates result in selective reduction in pulmonary hypertension. We hypothesized that a nebulized NONOate would improve oxygenation and reduce pulmonary vascular resistance in oleic acid-induced acute lung injury and pulmonary hypertension. Pigs underwent catheterization of the pulmonary artery, left atrium, and right atrium, and a flow probe was positioned around the pulmonary artery. Acute lung injury and pulmonary hypertension were induced with intravenous oleic acid. Animals were randomly assigned to receive either nebulized saline or the NONOate 2-(dimethylamino)ethylputreanine/NO (DMAEP/NO). Hemodynamic, gas exchange, pulmonary function, methemoglobin, and nitrite/nitrate measurements were obtained for 60 min. Animals in the DMAEP/NO group had improvement in PaO2 as compared with control animals (from 139 +/- 19 mm Hg to 180 +/- 19 mm Hg in the DMAEP/NO group [n = 6]; and from 144 +/- 6 mm Hg to 150 +/- 9 mm Hg in the saline group [n = 6], p < 0.05). After aerosol treatment, animals in the DMAEP/NO group had a greater reduction in pulmonary vascular resistance index (PVRI) than did control animals (from 81 +/- 17 dyne. s/cm5/kg to 34 +/- 8 dyne. s/cm5/kg; and from 104 +/- 16 dyne. s/cm5/kg to 64 +/- 11 dyne. sec/cm5/ kg in the saline group at 60 min, p < 0.05). There were no differences between the groups in systemic vascular resistance index (SVRI), cardiac index (CI), methemoglobin, nitrite/nitrate, or lung pathology scores. We conclude that DMAEP/NO improves oxygenation and has selective pulmonary vasodilating properties without causing significant systemic toxicity in this porcine model of acute lung injury.

Aerosolization of novel nitric oxide donors selectively reduce pulmonary hypertension.

OBJECTIVES: Inhaled nitric oxide (NO) reduces pulmonary hypertension in acute respiratory failure. Soluble nitric oxide donors (NO/nucleophile adducts-NONOates) are less cumbersome to deliver and may offer clinical advantage compared with inhaled NO. The objective of this study was to examine the pulmonary and systemic hemodynamic effects of tracheal aerosolization of a new class of NONOates in a porcine model of experimentally induced pulmonary hypertension. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratory. SUBJECTS: Yorkshire pigs (n = 18), weighing 11.4 to 16.4 kg. INTERVENTIONS: In anesthetized, mechanically ventilated, instrumented pigs, steady-state pulmonary hypertension (SSPH) was induced using a thromboxane agonist (U46619). Control animals received tracheal aerosolization of saline (n = 6); EP/NO animals received tracheal aerosolization of ethylputreanine NONOate (EP/ NO, n = 6); and DMAEP/NO animals received aerosolized 2-(dimethylamino) ethylputreanine NONOate (DMAEP/NO, n = 6). MEASUREMENTS AND MAIN RESULTS: Mean pulmonary (MPAP) and mean systemic arterial pressures (MAP), atrial pressures, cardiac output, and arterial blood gases were measured following drug instillation. DMAEP/NO animals had significant reductions in pulmonary vascular resistance index (PVRI) and MPAP at all time points compared with SSPH and control animals (p < .05), while systemic vascular resistance index did not change. EP/NO animals had a significant reduction in PVRI and MPAP at some time points compared with SSPH and control animals. For both NONOate-treated animal groups, MAP and cardiac index did not change significantly compared with SSPH and control animals (p < .05). CONCLUSIONS: In this porcine model of pulmonary hypertension, intratracheal aerosolization of soluble NO donors results in sustained reduction of pulmonary hypertension without reducing systemic arterial pressure. Intermittent aerosolization of NONOates may be an alternative to continuously inhaled NO in the treatment of acute pulmonary hypertension.

Intratracheal instillation of a novel NO/nucleophile adduct selectively reduces pulmonary hypertension.

We examined the pulmonary and systemic hemodynamic effects of administering soluble nitric oxide (NO) donor compounds (NO/nucleophile adducts, i.e., NONOates) directly into the trachea of animals with experimentally induced pulmonary hypertension. Steady-state pulmonary hypertension was created by using the thromboxane agonist U-46619. Yorkshire pigs were randomly assigned to one of four groups: group 1, intratracheal saline (control; n = 8); group 2, intratracheal sodium nitroprusside (n = 6); group 3, intratracheal ethylputreanine NONOate (n = 6); and group 4, intratracheal 2-(dimethylamino)-ethylputreanine NONOate (DMAEP/NO; n = 6). Pulmonary and systemic hemodynamics were monitored after drug instillation. Group 4 had significant reductions in pulmonary vascular resistance index (PVRI) at all time points compared with steady state and compared with group 1 (P < 0.05), whereas systemic vascular resistance index did not change. The mean change in mean pulmonary arterial pressure in group 4 was -33.1 +/- 1.2% compared with +6.4 +/- 1.3% in group 1 (P < 0.001), and the mean change in mean arterial pressure was -9.3 +/- 0.7% compared with a control value of -0.9 +/- 0.5% (P < 0.05). Groups 2 and 3 had significant decreases in both PVRI and systemic vascular resistance index compared with steady state and with group 1. In conclusion, intratracheal instillation of a polar-charged tertiary amine NONOate DMAEP/NO results in the selective reduction of PVRI. Intermittent intratracheal instillation of selective NONOates may be an alternative to continuously inhaled NO in the treatment of pulmonary hypertension.

Efficacy and safety of continuous albuterol nebulization in children with severe status asthmaticus.

We prospectively examined the efficacy and safety of continuous albuterol nebulization (CAN) therapy for children diagnosed with impending respiratory failure and status asthmaticus. Serum creatine phosphokinase (CPK) levels were measured, and other factors associated with cardiotoxicity were monitored. Seventeen patients (20 months to 17 years old) were enrolled in the study. No chest pain, arrhythmias, or signs of clinical deterioration occurred in any patient receiving CAN. No study subject required therapy with isoproterenol or mechanical ventilation. An elevation of total serum CPK was found in three patients; however, only one of these patients had an elevated (positive) CPK-MB isoenzyme fraction. We feel that CAN is safe for use in children diagnosed with status asthmaticus. Monitoring of serum CPK enzymes during CAN therapy is warranted until further studies have determined the significance of elevated CPK-MB isoenzymes in otherwise asymptomatic children treated for severe status asthmaticus.

Familial arteriovenous malformations in children.

Cerebral arteriovenous malformations are uncommon in children. Familial incidence of these lesions is reported in only 10 families. We report a family in which the two youngest siblings had this anomaly, and we review the literature. These cases represent a clinical situation that emergency physicians may encounter.

Epiglottitis in infants less than two years of age.

A retrospective review of 41 children less than two years of age was conducted to characterize the clinical presentation of epiglottitis in this young age group. Up to 25% of all cases of epiglottitis occur in children less than two years of age. The clinical presentation of patients in this young age group is variable. Signs and symptoms not routinely described in children over two years of age with epiglottitis but often observed in infants with epiglottitis include the absence of fever, the presence of only low grade fever, a significant history of antecedent URI, and a prominent "croupy" cough. These same features are often noted in children with the viral croup syndrome. A diagnosis of this life-threatening illness may be made promptly through an awareness of the presenting findings observed in infants. Young infants with epiglottitis can be safely managed with short-term nasotracheal intubation.