Does screening neonates in the neonatal intensive care unit for Pseudomonas aeruginosa colonization help prevent infection?

BACKGROUND: Pseudomonas aeruginosa (PA) is a Gram-negative environmental organism that can cause severe infection in immunosuppressed patients, including preterm neonates. In recent years, it has become common practice to screen neonates for PA colonization. AIM: To assess the value of screening neonates for PA in (1) predicting the risk of developing severe PA infection and (2) directing infection control practice. METHODS: Between August 2012 and September 2015, babies admitted to the neonatal intensive care unit (NICU) at North Bristol NHS Trust were screened routinely for PA colonization on admission and weekly thereafter. Data were also collected on babies who developed PA infection. Environmental samples from the NICU were tested for the presence of PA. Variable number tandem repeat (VNTR) typing was performed on all strains of PA from babies and the environment. FINDINGS: No babies with positive screens subsequently developed PA infection. There was no VNTR strain evidence supporting cross-infection from the environment or other babies. CONCLUSION: Screening neonates for PA did not identify babies who subsequently developed PA infection. Following cessation of screening in September 2015, there was no increase in the number of babies identified with PA infection.

Methacholine challenge in preschool children: methacholine-induced wheeze versus transcutaneous oximetry.

Tracheal/chest auscultation for wheeze and transcutaneous oximetry have both been suggested as measures of outcome in bronchial provocation tests in young children. This study aimed to compare the sensitivity and safety of these two techniques as end-points for methacholine challenge in children aged <4 yrs. Seventy-two methacholine challenges were performed in 39 children aged <4 yrs with recurrent wheeze. Arterial oxygen saturation (Sa,O2) and transcutaneous oxygen pressure tcPO2 continuously, and the test was terminated when wheeze was heard or at Sa,O2 <91%. tcPO2 was not used as an end-point. Wheeze or desaturation occurred at < or =8 mg x mL(-1) methacholine in every test. One child had transient clinical cyanosis, but no other ill-effects were seen. Fifty-six tests (78%) were terminated for wheeze, seven (10%) for fall in Sa,O2 and nine (12%) showed simultaneous responses in both parameters. Twenty-eight tests (39%) contained a fall in tcPO2 >3 kPa but six of these also showed a significant rise. Fifty-three tests (75%) contained a fall in tcPO2 >15%, but 20 of these also showed a significant rise. Tracheal/chest auscultation with Sa,O2 monitoring is a sensitive and relatively safe end-point for bronchial challenges in preschool children. The erratic pattern of transcutaneous oxygen pressure response in some children casts doubt on its reliability as a proxy measure of bronchial obstruction.

The bronchoprotective effect of inhaled salmeterol in preschool children: a dose-ranging study.

The optimal dose of salmeterol in infants and preschool children is not known. The aim of this study was to assess the bronchoprotective effect of different doses of salmeterol using methacholine-induced wheeze in children aged <4 yrs. Children <4 yrs old with a history of recurrent wheeze underwent two methacholine challenges within 7 days. One hour before each challenge they were pretreated in double-blind fashion using a metered-dose inhaler and Babyhaler spacer. Placebo was given before one challenge, and either 25, 50 or 100 microg of salmeterol before the other. Both the dose and treatment order were random. The provocative concentration of methacholine causing wheeze (PCwheeze) was measured on each occasion. Studies were terminated when wheeze occurred or arterial oxygen saturation (Sa,o2) fell below 91%. Of the 42 children enrolled, 33 completed the study. Two subjects refused the challenge test, two failed to return and five developed upper respiratory tract infections or wheeze between the two tests. The mean (range) age of the population was 27 (8-46) months. Ratios of PCwheeze between treatment and placebo challenges were calculated for each dosage group. The treatment/placebo ratios (95% confidence intervals) were 1.2 (0.6-2.4) for 25 microg, 2.5 (1.4-4.6) for 50 microg (p<0.01), and 4.0 (2.1-7.4) (p<0.001) for 100 microg doses. In recurrently wheezy children aged <4 yrs a single dose of salmeterol between 25 and 100 microg has a dose-dependent effect on methacholine-induced wheeze, and this is significantly different from placebo at 50 and 100 microg. This study suggests that the Babyhaler effectively delivers salmeterol to children <4 yrs of age and that doses between 50-100 microg are efficacious.

Respiratory distress syndrome in New Zealand: evidence from the OSIRIS trial of exogenous surfactant (Exosurf).

AIMS: To assess the impact, mortality, morbidity and economic costs, of respiratory distress syndrome severe enough to warrant ventilation in one year in New Zealand. METHODS: Review of data from all five New Zealand regional neonatal intensive care units' participation in the international OSIRIS trial of exogenous surfactant (Exosurf) treatment for respiratory distress syndrome (involving 6700 infants in 21 countries), and extrapolation of these data to a full year. RESULTS: There were 265 New Zealand infants entered in the OSIRIS trial; the mean birthweight was 1335 g and mean gestation 29 weeks; 61% of infants were less than 30 weeks gestation. Forty-seven infants (17.7%) died prior to discharge from hospital, 40 deaths being attributed to prematurity or respiratory distress syndrome. One hundred and two infants (38.5% of the cohort; 45% of surviving infants) were oxygen dependent and 36 infants (13.6%) were dead at 28 days of age. Thirty-four infants (12.8% of the cohort; 15% of surviving infants) were oxygen dependent and 40 infants (15%) were dead at the expected date of delivery. Infants were intubated for a mean 12.5 days, with surviving infants of less than 27 weeks gestation intubated for a disproportionately long period of time. Seventy-two infants (29% of the 246 infants examined) had an abnormality detected by cranial ultrasound scan at 1 or 6 weeks of age and in 23 (9%) this was a major abnormality. Of surviving infants 16 (7.5% of 213 examined) had a major abnormality on cranial ultrasound scan. Amongst infants at high risk for respiratory distress syndrome (gestation less than 30 weeks) 53% received antenatal steroids, compared with 22% in the OSIRIS trial overall. In a full year the cost of caring for infants with respiratory distress syndrome sufficiently severe enough to warrant ventilation is estimated to be NZ$12.5 million. The average cost of caring for a surviving infant was roughly NZ$52,500 and a nonsurviving infant was NZ$24,500. CONCLUSIONS: In a full year (total births 60,000) approximately 350 New Zealand infants may require ventilation for respiratory distress syndrome. Increasing the percentage of infants who receive antenatal steroids is likely to be extremely cost effective. In the era of antenatal steroids and exogenous surfactant, 85% of infants with respiratory distress syndrome requiring ventilation survive to discharge home and over 90% of survivors are likely to be healthy normal adults.

Structure and function of the carotid body in New Zealand genetically hypertensive rats.

Morphology of the carotid body and the ventilatory response to hypoxia were compared in New Zealand genetically hypertensive rats and 'normotensive' control rats from the same genetic stock. Hypertensive rats grew more slowly, had higher blood pressure from 6 weeks of age and developed left ventricular hypertrophy. Carotid bodies of both groups were similar in size but larger than those of a common Wistar strain. Intimal damage and proliferation were seen in 1st- and 2nd-order branches of the carotid body artery in hypertensive rats and point-counting showed that the volume proportion of Type 1 cell nuclei and vascular lumen was reduced and vascular wall increased. In age-matched anaesthetized rats, minute ventilation per 100 g was greater in hypertensives than 'normotensive' when inspiring O2 concentrations of 30, 21, 18, 15, 12, 10 and 8%. However, at each inspired O2 concentration, arterial Pa.O2 was higher and Pa.CO2 lower in hypertensive than in 'normotensive' rats. Hypertensive rats were hyperventilating. The shape of the ventilation/O2 tension curve was similar in hypertensive and 'normotensive' rats; thus carotid body sensitivity to hypoxia was probably unchanged. Possible causes of hyperventilation and the relation of carotid body morphology to hypertension are discussed.

Dopamine and ventilatory effects of hypoxia and almitrine in chronically hypoxic rats.

We hypothesized that the temporary blunted ventilatory response to hypoxia seen in chronically hypoxic rats could be related to the increased amount of dopamine found in their carotid bodies. Rats, kept 2-3 wk in 10% O2, showed reduced nonisocapnic ventilatory responses to 21-12% inspiratory O2 fraction compared with control rats. Stimulus-response curves to almitrine, which simulates the action of hypoxia on the carotid body, were also depressed in chronically hypoxic rats. Responses to hypoxia and almitrine were significantly correlated in the two groups of rats. Dopamine depressed ventilation during normoxia, hypoxia, and almitrine stimulation in both groups, an action abolished by the dopamine-2 antagonist domperidone. Domperidone slightly increased responses to hypoxia and almitrine in control rats but had a greater enhancing effect in chronically hypoxic rats, such that there was no longer a difference between the responses of the two groups.

Effect of almitrine bismesylate on breathing pattern during hypoxia/hypercapnia in rats and ferrets.

1. Ventilatory measurements and functional residual capacity (FRC) were recorded from anaesthetized rats and ferrets using a whole body plethysmograph. Simulation of aspects of human chronic obstructive airways disease (COAD) was attempted by making animals acutely hypoxic or hypoxic and hypercapnic by causing them to breath appropriate gas mixtures or by increasing the tracheal resistance or dead-space. Some chronically hypoxic rats, which have muscularized pulmonary arterioles similar to COAD patients, were also studied. 2. In 18 chronically hypoxic (CH) rats and 17 littermate control rats (C), breathing air, doses of almitrine bismesylate caused greater increases in ventilation (VE) in C than in CH rats. FRC, which was initially greater in CH rats, increased significantly in both groups after almitrine. 3. In C rats, breathing hypoxic or hypoxic/hypercapnic gas mixtures caused large increases in VE. Slow infusions of almitrine caused a further increase in VE usually via an increase in tidal volume (VT) but not frequency (f). 4. In two series of rats (n = 9; n = 6) severe and moderate degrees of tracheal obstruction caused a fall in PaO2 and a rise in PaCO2, a fall in VE due to both VT and f and large changes in oesophageal pressure (Poes), which often became positive on expiration. Almitrine infusions usually caused a rise in PaO2, a rise in VT and no change in f; with moderate obstruction, Poes also rose. The results were thought to depend on the balance between improved ventilation and increased O2 demand of the respiratory muscles. 5. Eleven ferrets were made hypoxic and hypercapnic by adding a large dead-space to the trachea. A slow infusion of almitrine caused a significant rise in PaO2 before any significant change in VE was detected; PaCO2 fell at some time during the infusion, but not significantly. The initial significant rise in PaO2, at 2.5 min, was not associated with significant changes in T1 (time of inspiration) and VT/TI. At 5 min VT/TI and PaO2 were all significantly altered. 6. Infusions of almitrine into hypoxic and hypercapnic animals caused improvements in the arterial oxygen tension which were associated with subtle changes in the breathing pattern; inspiratory time and inspiratory flow rate changed in the absence of an increase in total VE. Possible conclusions with respect to the action of almitrine in patients with COAD are discussed.

Effect of alveolar pressure on pulmonary artery pressure in chronically hypoxic rats.

The effect on pulmonary artery pressure of a rise in alveolar pressure differed in chronically hypoxic rats (10% O2 for 3-5 weeks) compared with control rats. Chronically hypoxic rats have newly muscularised walls in arterioles in the alveolar region. Isolated lungs of chronically hypoxic and control rats were perfused with blood under conditions in which alveolar pressure was greater than left atrial pressure during both normoxia and hypoxia. Alveolar pressure was the effective downstream pressure. Pressure-flow lines were measured at low and high alveolar pressure (5 and 15 mmHg). During normoxia pressure-flow lines of chronically hypoxic rats had a steeper slope (higher resistance) and greater extrapolated intercept on the pressure axis (effective downstream pressure) than control rats. In both groups of rats the change from low to high alveolar pressure during normoxia caused an approximately parallel shift in the pressure-flow line similar to the change in alveolar pressure. During hypoxia, which led to an increase in slope and intercept in both groups of rats, the effect of a rise in alveolar pressure differed in chronically hypoxic from control rats. In control rats there was a small parallel shift in the pressure-flow line that was much less than the increase in alveolar pressure; in chronically hypoxic rats there was a large parallel shift in the pressure-flow line that was greater than the increase in alveolar pressure. Thus in chronically hypoxic rats hypoxic vasoconstriction probably occurred mainly in muscular alveolar vessels, whereas in control rats it probably occurred upstream in extra-alveolar vessels. At constant blood flow the relation between pulmonary artery pressure and alveolar pressure was measured while alveolar pressure was reduced from approximately 15 mmHg to zero during both normoxia and hypoxia. In control and chronically hypoxic rats the slope of this line was less than 1. At an alveolar pressure of 2-3 mmHg there was an inflection point below which the line was nearly horizontal in control but negative in chronically hypoxic rats. During hypoxia the inflection point increased in control but not in chronically hypoxic rats, whereas the preinflection slope became negative. Apart from a rise in pulmonary artery pressure at all values of alveolar pressure, which occurred in both groups of rats, there was no change in the form of the curve in chronically hypoxic rats during hypoxia. These results also suggest constriction of extra-alveolar vessels in control rats and alveolar vessels in chronically hypoxic rats during hypoxia.

Action of almitrine bismesylate on ventilation-perfusion matching in cats and dogs with part of the lung hypoventilated.

Ventilation to one lobe of lung was reduced in anaesthetized open-chest cats and dogs to simulate the ventilation/perfusion (V/Q) mismatching of chronic lung disease. Blood flow to this lobe fell less than ventilation; thus lobar V/Q diminished. In seven cats almitrine (0.5 mg/kg + 10 micrograms/kg per min, i.v.) caused a rise in pulmonary artery pressure (PPA), increased flow through the hypoventilated lobe in six out of seven cats and both increased or decreased lobar vascular resistance (PVR); the lobar V/Q ratio therefore fell. Arterial and lobar venous oxygen tension (PO2) fell. In five dogs almitrine caused a rise in PPA and PVR but lobar flow changes were variable. Arterial and lobar venous PO2 fell. With fixed ventilation, almitrine failed to improve V/Q matching; there was no improvement in gas exchange in the hypoventilated lobe. In eight dogs the hypoventilated lobe was perfused at constant flow with right atrial blood (i.e. while V/Q was held constant). Almitrine caused a rise in perfusion pressure, vasoconstriction, followed, in five out of eight dogs, by vasodilatation. In six similar cat preparations, vasoconstriction but not vasodilatation was clearly shown. In two cats dilatation after almitrine was demonstrated during ventilation with Nitrogen. In all experiments there was no significant effect of the solvent. Thus the dual action of almitrine seen in other species was seen in a proportion of cats and dogs. Results do not support the view that improved arterial gas tensions in patients after almitrine are attributable to diversion of blood flow away from hypoxic lung. Alternative mechanisms are discussed.

Vago-vagal reflexes to the colon of the anaesthetized ferret.

Electrical stimulation of the central end of the vagal communicating branch in the thorax at frequencies between 2 and 20 Hz elicited, after a latency of 7.2 +/- 0.8 s, large-amplitude colonic contractions. 5 Hz stimulation gave near maximal contractions and, because vomiting was more likely to occur at higher stimulus frequencies, was used as the standard stimulus for subsequent experiments. At this frequency the peak colonic contraction was 6.5 +/- 0.9 kPa. Following atropine the characteristics of the response to central vagal stimulation differed from that seen before atropinization. The latency was longer (45.7 +/- 8.2 s) and the amplitude greatly attenuated (0.7 +/- 0.2 kPa). Cooling the vagus nerves to 2 degrees C at a level either above or below the site of stimulation completely abolished both the cholinergic and the atropine-resistant colonic responses to central vagal stimulation. These results are consistent with the vagus containing two motor pathways to the colon which are reflexly stimulated by a vagal afferent input. The functional significance of these reflexes is discussed.

Hypoxic pulmonary vasoconstriction in chronically hypoxic rats.

Reactivity of lung vessels to acute hypoxia was found increased or decreased in chronically hypoxic (CH) rats by different authors. We examined severity and duration of hypoxia and age as possible explanations. Isolated blood-perfused lungs of CH rats ventilated with low-O2 mixtures were compared with control (C) rats. Juvenile CH rats (10 or 12% O2, 3 weeks) showed increased reactivity; reactivity of mature CH rats (10% O2, 3 weeks) was not significantly different from controls. Reactivity declined with age in CH but not C rats. Juvenile and mature rats exposed to 10% O2 for 48 h showed reduced reactivity; after 3 weeks but not 48 h hypoxia, pulmonary arterioles are narrowed by new muscle. The pressure/flow relationship differed in CH from C rats in that resistance and critical closing pressure (CCP) were greater during normoxia. Hypoxia caused increased resistance and CCP in C rats but mainly an increase in CCP in CH rats. The difference may be attributable to muscularisation of collapsible alveolar vessels in chronic hypoxia.

Contribution of polycythaemia to pulmonary hypertension in simulated high altitude in rats.

A rat model was used to assess the viscosity factor in pulmonary hypertension of high altitude. Rats exposed to 10% O2 for three weeks developed increased pulmonary vascular resistance (p.v.r.) and polycythaemia; the haematocrit (Hct) was 50-60%, values similar to those in normal men at high altitudes. The contribution of high Hct to the increased p.v.r. was assessed in isolated perfused lungs of chronically hypoxic rats perfused with their own high Hct blood, or normal Hct blood from control rats. Pressure/flow relationships were measured over a wide range and the slope (P/Q) of this relationship and its extrapolated intercept on the pressure axis were increased by high Hct blood. A return to low Hct blood did not restore initial conditions although a second perfusion with high Hct blood again increased p.v.r. and intercept. Lack of reversibility was attributed to changes with time in blood or lung. In a second experiment designed to eliminate time changes, chronically hypoxic or litter-mate control rats were each perfused with only one blood, their own or each other's and P/Q relations were rapidly measured. The P/Q slope and pressure intercept increased progressively in the following groups: control rats perfused with their own blood (Hct 34%), control rats perfused with chronically hypoxic blood (Hct 56%), chronically hypoxic rats perfused with control blood (Hct 35%) and chronically hypoxic rats perfused with chronically hypoxic blood (Hct 53%). To exclude factors in chronically hypoxic blood other than high Hct which might increase p.v.r., control rats were perfused with blood of different Hct obtained by centrifugation. High Hct again increased p.v.r. There was a significant relationship in all rats between pulmonary artery pressure (Ppa), which takes into account both P/Q slope, intercept and Hct. There was substantial batch variation which may reflect sensitivity to hypoxia. In chronically hypoxic rats with high Hct blood, Ppa varied from 29-47 mmHg; with low Hct blood the range was 26-38 mmHg. Comparable values for control rats were 21-29 and 17-20 mmHg. We conclude that the polycythaemic blood of chronic hypoxia contributes substantially to pulmonary hypertension. Where it is excessive, it may prejudice tissue blood flow.

Does almitrine bismesylate improve V/Q matching? An animal study.

Pulmonary vascular actions of almitrine bismesylate were studied in ferrets, rats, cats and dogs in conditions which simulated those of patients with hypoxic lung disease. All or part of a lung was made hypoxic or hypoventilated so that affected vessels were constricted. Rats were made chronically hypoxic (10%, O2, normobaric chamber). In vivo and isolated preparations were used. In all preparations and species almitrine bismesylate caused vasoconstriction in normoxia, constriction followed by dilation in hypoxia or hypoventilation. In hypoventilated lung there is ventilation/perfusion mismatching which was not improved by almitrine bismesylate . Ventilatory measurements in chronically hypoxic/hypercapnic rats showed that almitrine bismesylate increased tidal volume but not frequency. It is uncertain whether vascular (Q) or small ventilatory (V) changes are the cause of the improved gas tensions and V/Q matching in patients with chronic obstructive lung disease receiving almitrine bismesylate .