Yasushi Ohki

Complications of percutaneously inserted central venous catheters in Japanese neonates

Background: To determine institutional policies concerning percutaneously inserted central venous catheter (PICC) utilization and also frequencies of complications such as pericardial effusion (PCE), cardiac tamponade (CT), pleural effusion, ascites, venous thrombosis, and catheter removal difficulties.

Complications of peripherally inserted central venous catheter in Japanese neonatal intensive care units

The aim of this study was to investigate the incidence and risk factors of peripherally inserted central venous catheter (PICC)‐related complications using a multicenter case survey.

Ultrasonographic detection of very thin percutaneous central venous catheter in neonates.

To assess the ability of ultrasonography to detect the tip of a very thin (0.4 mm outer diameter) percutaneous central venous catheter (PCVC) in neonates, the PCVC tip location was assessed by ultrasonography (US) and compared to the location estimated by standard radiography for 57 PCVCs in 44 neonates. Of 57 occasions, the examiner could not find the PCVC tip in three cases (5%). In the remaining 54 instances, in 87% of cases, the PCVC tip position was consistent with the location implied by skeletal landmarks on standard radiographs. On 24 occasions we also assessed catheter tip dislodgement according to flexion and extension of the infants arm. US could detect 78% of cases of catheter tip dislodgement. The PCVC tip was sometimes visualized as a dot and parallel lines as well as mere parallel lines. In a large population of cases, US is a reliable method for detection of a thin PCVC tip. US provides precise information about the PCVC tip position in relation to vascular structure and contributes to safer positioning of the PCVC than traditional radiography alone.

Hepatocyte growth factor treatment improves alveolarization in a newborn murine model of bronchopulmonary dysplasia.

Background: Bronchopulmonary dysplasia (BPD) is thought to be one form of developmental arrest of the lung. Hepatocyte growth factor (HGF) participates in normal lung growth and in lung regeneration. Objectives: The purpose of this study is to investigate whether HGF can improve alveolarization and attenuates functional abnormalities of a murine model of BPD induced by hyperoxia. Methods: Three-day-old CD-1 mice were exposed to 90% of oxygen or room air (control group) for 7 days. These animals were then kept in room air for the next 7 days. Recombinant human (rh) HGF (100 μg/g b.w., divided 3 times, rhHGF group) or vehicle (vehicle group) was administered intraperitoneally during hyperoxia. On day 17, the pulmonary function test and bronchial hyperresponsiveness (BHR) were examined. Mean linear intercepts (MLI) were measured as parameters of alveolarization. Cell renewal (on day 10) and vascularization of the lung were also evaluated. Results: Exposure to hyperoxia induced increased airway resistance and BHR. These animals showed a severely simplified alveolar structure, increased MLI, decreased cell renewal (16.1 ± 2.4 vs. 29.6 ± 2.4%, p < 0.05), and decreased vascularization (15.1 ± 0.3 vs. 18.4 ± 1.5 vessels/hpf, p < 0.05, vehicle vs. control group, respectively). rhHGF treatment during exposure to hyperoxia significantly reduced all of these changes (27.9 ± 1.7%, 18.2 ± 0.5 vessels/hpf for cell renewal and vascularization, respectively; all values are p < 0.05 against vehicle animals). Conclusion: HGF partially protects against the inhibition of alveolarization and improves functional abnormality in the hyperoxia-induced neonatal mice model of BPD.

Lack of transient receptor potential vanilloid-1 enhances Th2-biased immune response of the airways in mice receiving intranasal, but not intraperitoneal, sensitization.

Background: Transient receptor potential vanilloid-1 (TRPV1) may modulate allergic airway inflammation because it is expressed not only on the nerve endings but also on several cells of the immune system. We wanted to know the characteristics of airway and systemic responses against sensitization and challenge with allergens in TRPV1 receptor gene knockout mice (TRPV1–/–). Methods: TRPV1–/– and their wild-type counterparts (TRPV1+/+) were sensitized with either house dust mite (HDM) or ovalbumin (OVA) via intranasal (i.n.) or intraperitoneal (i.p.) route before the final i.n. challenge with the corresponding allergen. One day after the final challenge, serum IgE levels, cytokine levels in the bronchoalveolar lavage fluid (BALF), and the number of BALF cells were examined after measuring bronchial hyperresponsiveness against methacholine. Results: Compared to TRPV1+/+, TRPV1–/– showed enhanced Th2-biased response after i.n. HDM or OVA sensitization, including increased levels of serum IgE, interleukin 4 (IL-4) and eosinophils in the BALF. By contrast, when sensitized via i.p. route, the response against OVA or HDM was almost similar between TRPV1+/+ and TRPV1–/–. Conclusion: TRPV1 receptor may downregulate Th2-biased immune response when sensitized via airways, although this was not the case when sensitized systemically.

Characteristic Features of Allergic Airway Inflammation in a Murine Model of Infantile Asthma

Background: The pathophysiology of infantile asthma may differ from that in older children or in adults, partly because of the different immune response depending upon maturation. In adult mice, the sensitizing dose of antigen is known to be critical to the polarized development of helper T cell subsets and allergic airway inflammation. We wanted to know the characteristics of allergic airway inflammation of infantile asthma by developing a murine model. Methods: BALB/C mice at different stages of maturation (juvenile: 3 days after birth; adult: 8 weeks of age) were sensitized with 10 or 1,000 µg ovalbumin (OVA) or vehicle. The animals were then challenged with aerosolized OVA or saline once a day during 6 consecutive days. After the final challenge, bronchial hyperresponsiveness (BHR), bronchoalveolar lavage fluid (BALF), histological changes in the airways and immunological status were examined. Results: In both juvenile and adult animals, sensitization with 10 µg OVA induced the T helper 2 response (elevated IL-4 and decreased IFN-γ levels). BHR, airway eosinophilia, the inflammatory cell infiltration, goblet cell metaplasia (GCM), and IgE antibody production were more prominent in animals given this dose than 1,000 µg OVA. Among these responses, GCM as well as BALF IL-4, and BHR were comparable between juvenile and adult animals, whereas other parameters were lower in juvenile animals, especially in those given 1,000 µg OVA. Conclusion: GCM and, consequently, airway mucus hypersecretion may be an important component of allergic airway inflammation in infantile asthma.

Transcutaneous oxygen tension measurements during methacholine challenge of prematurity in infants with chronic lung disease.

Chronic lung disease (CLD) of prematurity may be caused by a number of insults during mechanical ventilation, including barotrauma and hyperoxia. To evaluate bronchial hyperresponsiveness (BHR) in infants with CLD of prematurity, we measured changes in transcutaneous oxygen tensions (tcPO2) during methacholine inhalation challenge. Twelve infants with CLD and 22 age‐matched children without respiratory diseases were enrolled in this study (ages—5 to 36 months; mean age—16.2 months). Serial doses of methacholine were doubled until a 10% decrease in tcPO2 from baseline was reached. The cumulative dose of methacholine inhaled by the time tcPO2 had been reached (Dmin‐PO2) was considered to represent the dose at which reactivity to methacholine (RO2meth) had occurred.

The effect of aerosolized furosemide in infants with chronic lung disease

To investigate whether aerosolized furosemide would improve pulmonary function in premature infants with chronic lung disease, we enrolled eight preterm ventilator‐dependent infants in a cross‐over, double‐blind. placebo‐controlled trial. Either aerosolized furosemide (2mg/kg) or placebo (0.9% saline) was administered, and serial pulmonary function tests were performed before and at 1 and 2h after each inhalation. After furosemide inhalation, static respiratory compliance increased significantly by 24.3% and 23.2% as percentage change from the baseline value at 1 and 2h (p= 0.014 and 0.022, respectively). Also, tidal volume increased significantly by 33.8% and 28.7% at 1 and 2h, respectively (p= 0.004 and 0.009). In contrast, no changes were observed in them after placebo inhalation. Total respiratory resistance was unchanged after both furosemide and placebo inhalation. There were no differences in urine volume in two groups. These data suggested that aerosolized furosemide improved pulmonary function in infants with chronic lung disease without excessive diuresis.

PERCUTANEOUS CENTRAL VENOUS CATHETERIZATION VIA THE GREAT SAPHENOUS VEIN IN NEONATES

In 44 neonates (mean birthweight 1207 g and mean gestational age 30.0 weeks), very small central venous catheters were percutaneously inserted via the great saphenous vein on 46 occasions. Catheter‐related complications such as catheter blockages in 17 (37%), edema in a unilateral leg in three (6%), and mechanical disruption in two (4%) were noted. Although two of the neonates were found to have bacteremia and five neonates died, none were catheter related. The optimal length of catheter insertion (Y) from the great saphenous vein at the level of the medial maleollus to the inferior vena cava at T9 and L3 was calculated by regression equations utilizing total body length (X). Radiographs taken with extended and flexed leg postures revealed that the catheter tips were retracted with extension of the lower extremities and the degree of displacement ranged from 1 to 4 (mean 2.7) vertebral levels. Because this movement might cause migration into veins that connect to the inferior vena cava, the catheter tip should be located between T9 and L3, except at the renal vein junction. Percutaneous central venous catheterization via the great saphenous vein is safe and useful. Regression equations provided for rapid estimation of the optimal length of insertion.

Elevated Type IV Collagen in Bronchoalveolar Lavage Fluid from Infants with Bronchopulmonary Dysplasia

We measured the levels of type IV collagen and lipid peroxides in bronchoalveolar lavage fluid (BALF) from infants with respiratory distress syndrome (RDS) to determine the relationship to the development of bronchopulmonary dysplasia (BPD). We analyzed their levels between two groups, RDS infants who developed BPD (n = 8, BPD group) and those who did not (n = 11, RDS group). The levels of the type IV collagen in the BPD group were significantly higher than those in the RDS group at 3 and 7 days of age (p = 0.0024). In the BPD group, persistently increased levels of the type IV collagen were observed during the period up to 14 days of age. There was a positive relationship between the type IV collagen levels and polymorphonuclear leukocyte counts, and thiobarbituric acid-reactive substance levels in BALF. These results suggest that the increased type IV collagen levels in BALF of BPD infants may reflect pulmonary basement membrane damage and the involvement of oxygen metabolites in its process.