Michael F. Hird

Gas trapping during high frequency positive pressure ventilation using conventional ventilators

Inspiratory and expiratory volumes were measured in 51 preterm infants with respiratory distress syndrome (RDS), when comparing two ventilator rates, 60 and 120 breaths/min. Gas trapping was not demonstrated at rates of 60, but in 11 infants at 120 breaths/min and this was more common in the paralysed infants and those more mature than 31 weeks gestational age (P less than 0.05). The median change in functional residual capacity resulting from gas trapping was 3.8 ml/kg. We conclude rates of 120 breaths/min can be used in the majority of non-paralysed infants without gas trapping but should be avoided in paralysed infants more mature than 31 weeks.

Randomised controlled trial of albumin infusion in ill preterm infants

We assessed the effect of albumin infusion on weight loss and ventilation requirement in sick premature infants. Thirty infants, median gestational age 29 weeks, were entered into a randomised controlled trial, at a median of 2 days of age. The infants, all with an albumin level <-30 g/l, received either 5 ml/kg of 20% albumin or 5 ml/kg of their maintenance fluids (placebo), both given as part of the total daily fluid requirement. The response to the infusion was assessed by comparing two periods; 12 h immediately prior to the infusion and 12–24hh after the infusion. Albumin infusion was associated with a significant increase in albumin level and a significant reduction in weight, but in the placebo group there was a significant increase in weight. There were, however, no significant changes in the peak inspiratory pressure in response to either infusion. There was only a modest reduction (<15%) in the inspired oxygen concentration, which occurred in both groups, but reached statistical significance only following the albumin infusion. We conclude that our results suggest that albumin infusion in “hypoalbuminaemic” sick preterm infants is unlikely to alter their respiratory status.

Inflating pressures for effective resuscitation of preterm infants

The magnitude of inflating pressure necessary for effective resuscitation was examined in 70 preterm infants. The median pressure to cause adequate chest wall expansion was 22.8 cmH2O; no infant required a peak inflating pressure greater than 30 cmH2O. No further increase in inflation pressure was used during resuscitation and the median 5- and 10-min Apgar scores were 8 and 9, respectively.

Nosocomial bacterial infections in very low birth weight infants.

The occurrence of congenital and nosocomial bacterial septicaemia has been documented by identifying the number of positive blood cultures by reviewing the laboratory and clinical records of 394 very low birth weight infants who were consecutively admitted to a neonatal intensive care unit over a 40-month period. The incidence of congenital septicaemia was 6% and of nosocomial septicaemia 17%. The commonest causes of congenital infection wereStreptococcus agalactiae Staphylococcus epidermidis andEnterococcus faecalis (each in 18% of cases). The commonest cause of nosocomial infection wasS. epidermidis (51% of cases), except in infants of birth weight less than 750 g. Risk factors for nosocomial infection were extremely low birth weight, very preterm birth and prolonged ventilation. Nosocomial infection was associated with significantly lengthened hospital admission.

Airway pressure triggered ventilation for preterm neonates

The usefulness of airway pressure triggered ventilation for the preterm newborn has been assessed using a new patient triggered valveless ventilator, the SLE 2000 infant ventilator (SLE 2000). This ventilator performs well at fast rates with no inadvertent positive end expiratory pressure (PEEP) even at rates of 150 breaths per minute (bpm). The ventilator is triggered by a change in airway pressure equal to or exceeding 0.5 cmH2O. If the infant fails to achieve the change in airway pressure which will trigger the ventilator the infant is ventilated at the back-up rate which is predetermined in conventional mode prior to commencing PTV. Infants were ventilated for one hour on a conventional neonatal ventilator, then for one hour on the SLE 2000 in conventional mode without changing the ventilator settings and finally for one hour on the SLE 2000 in patient triggered mode. Arterial blood gases were checked at the end of each hour. During patient triggered ventilation (PTV) the peak pressure, inspiratory time and inspired oxygen concentration were the same as those used during conventional mode. Simultaneous recordings were made of flow, volume, ventilator and oesophageal pressure change, from this recording the trigger delay during PTV was calculated. The trigger delay, being the time lag from the start of spontaneous inspiration, indicated by the negative deflection in the oesophageal pressure trace, and the onset of the ventilator breath. Thirteen infants were included in the study, median gestational age 32 weeks (range 25-35) and birthweight 1640 g (range 838-3038). All were being ventilated for respiratory distress syndrome (RDS) and were 4 days of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Causes of failure of neonatal patient triggered ventilation

Causes of failure of patient triggered ventilation (PTV) in neonates have been determined. In particular we have investigated the importance of the timing of ventilator inflation in the spontaneous respiratory cycle and hence the respiratory interaction provoked during PTV. Fifty-six infants (median gestational age 29 weeks) were studied on 63 occasions using two different trigger systems, changes in airway pressure and airflow. After one hour of PTV, only 26 infants were synchronous (inflation coinciding with and occurring only in inspiration), 8 were apnoeic. In the remaining 29 infants, inflation extended into expiration, five of whom were actively expiring. The timing of inflation in the spontaneous respiratory cycle and the interaction provoked was significantly related to the trigger delay, but not the inflation time or type of trigger used. Oxygenation after one hour of PTV improved in infants in whom inflation occurred in inspiration only and in some when it extended beyond. Failure of long term PTV was more common, however, in infants in whom inflation extended beyond inspiration (i.e. asynchronous), but this did not relate to the type of trigger used. Failure was also associated with a long trigger delay (P less than 0.01), a very short inflation time (P less than 0.01) and commencement of PTV early in the infants illness (P less than 0.05). We conclude that synchrony is the most beneficial respiratory interaction during PTV. Our data suggest that this interaction would be more consistently provoked by the use of a sensitive triggering system which ensured a short trigger delay.

Home oxygen therapy following neonatal intensive care

In a 12-month period 28 of 164 consecutive very low birthweight (VLBW) infants receiving intensive care within 48 h of birth at Kings College Hospital developed chronic lung disease, (oxygen dependence beyond 28 days of age). Fifteen of the 28 infants were eligible for home oxygen therapy, but this was only practical, because of home circumstances, in 8 infants (4.9%). These 8 infants received home oxygen therapy. One further infant, born at term and suffering from pulmonary hypoplasia was also discharged home on oxygen therapy. Two infants subsequently required readmission due to a deterioration in their respiratory status and died. Three others required re-admissions (total duration 32 days) for respiratory problems. The median duration of home oxygen therapy was 17 weeks (range 4-486 days). We conclude that home oxygen therapy is needed by only a very small number of preterm infants and is appropriate for only a proportion of them. Parents need to be counselled carefully regarding the possibility that the need for oxygen might be protracted.

Randomised trial of patient triggered ventilation versus high frequency positive pressure ventilation in acute respiratory distress.

Synchronous respiration during mechanical ventilation of preterm neonates with acute respiratory distress is extremely beneficial as it improves oxygenation and is associated with a very low incidence of pneumothorax. We have assessed which form of ventilation: patient triggered ventilation (PTV) or high frequency positive pressure ventilation (HFPPV) is most successful in provoking this beneficial respiratory interaction, synchrony. Preterm infants of less than 4 hours of age and gestational age greater than or equal to 27 weeks were entered into a randomised controlled trial. Thirteen patients received PTV, median gestational age 30 weeks (range 27-36) and 36 HFPPV, median gestational age, 29 weeks (range 27-40). HFPPV was delivered by Sechrist ventilators at rates between 61 and 120 breaths/minute. Patient triggered ventilation was delivered by an SLE ventilator and an airway pressure trigger was used. Inflation times during PTV were between 0.2 and 0.45 seconds. HFPPV provoked synchrony which persisted until extubation in 25 patients, but PTV provoked persistent synchrony only in four patients (p less than 0.05). No infant developed a pneumothorax. Eleven of 36 patients became asynchronous on HFPPV and 5 of 13 on PTV. In addition, four patients on PTV developed recurrent apnoea with deteriorating blood gases. Thus, 11 of 36 patients on HFPPV and 9 of 13 on PTV required transfer to conventional ventilation (p less than 0.05). Transfer occurred at a median of 30 hours (range 6-84) on HFPPV and 1 hour (range 1-25) on PTV, p less than 0.01. Infants who required transfer from the randomised mode of ventilation required a longer period of intubation (median 174 hours, range 30-2928) compared to 38 hours (range 1.5-456) for successful cases, regardless of randomisation (p less than 0.01). This study demonstrates PTV is significantly less successful in promoting synchrony than HFPPV. We therefore conclude HFPPV is a more useful form of respiratory support than PTV for preterm infants with acute respiratory distress.

Comparison of different rates of artificial ventilation for preterm infants ventilated beyond the first week of life

The effect on blood gases of different ventilator rates in preterm infants ventilated beyond the first week of life was assessed. Seventeen infants, median gestational age 25 weeks, were studied at median postnatal age of 11 days. The infants were ventilated through a set sequence of rates: 30, 60, 30, 100 and 30 breaths per min (bpm), each rate being maintained for 20 min. Peak and positive end expiratory pressure and I:E ratio (1:1) were unchanged at each rate and mean airway pressure was kept constant by altering flow as necessary. No significant change in oxygenation was demonstrated at either rates of 60 or 100 bpm compared to 30 bpm. PaCO2 levels were, however, significantly reduced at 60 bpm (P less than 0.001) compared to 30 bpm; but this improvement in PaCO2 was not seen at 100 bpm. These results suggest that increasing ventilator rate higher than 60 bpm in the majority of infants ventilated after the first week of life is not advantageous.

Some autonomic blocking properties of zetidoline (DL 308-IT), a novel potential anti-psychotic drug

PAUL FOSBRAEY, MICHAEL F. HIRD, E. STEWART JOHNSON*, Department of Pharmacology, Kings College, Strand, London WCZR 2LS. U.K. Zetidoline [DL 308-IT (I-(3-chlorophenyl). 3-[-2-(3,3no affinity for ,!3,-adrenoceptors. Cumulative dosedimethyl-1-azetidinyl ethyl]imidazolidin-2-one hydroresponse curves to the relaxant effect of isoprenaline chloride)] is a novel centrally acting dopamine antaon the inherent tone of the guinea-pig isolated tracheal gonist, which inhibits apomorphine-induced emesis and spiral preparation were similarly unaffected by DL 308stereotypy in the dog, amphetamine stereotypy in the IT. rat, prevents conditioned avoidance responses and On the longitudinal muscle of the guinea-pig isolated increases the turnover of dopamine in rat brain (see Szabadi et a1 1980; Barone et al 1982). In healthy volunteers both DL 308-IT and thioridazine displayed sedative properties, caused miosis, hypotension and a decrease in salivation although in equisedative doses DL 308-IT had a smaller influence on autonomic functions than thioridazine (Szabadi et a1 1980). Szabadi et a1 (1980) considered that DL 308-IT (10, 20 mg) caused miosis possibly through an a-adrenoceptor antagonist action although with the smaller of the two doses used they noted an increase in sweating and heart rate which they considered to be a sympathomimetic iction of the drug. The decrease in salivation was considered to indicate an anti-acetylcholine effect. It was of interest therefore to identify the peripheral autonomic blocking properties of the new drug on isolated organ preparations in vitro. Cumulative dose-contractile response curves were made for phenylephrine on the rabbit and guinea-pig aortic spiral preparations and repeated after 30 min incubation with different concentrations of DL 308-IT (1, 10, 40 and 100 p ~ ) . On the rabbit aorta, increasing concentrations of DL 308-IT displaced the log dose-response line of phenylephrine to the right in a parallel manner indicating competitive antagonism of postsynaptic a,-adrenoceptors. The antagonism was quantified by the method of Arunlakshana & Schild (1959) to give a pA2 value of 5.99 (slope function -0.93; pA2-pAlo 1.02). Similar results were obtained for DL 308 IT against phenylephrine on the guinea-pig aorta (pA2 5.82; slope funcileum dose-contractile response curves to histamine were displaced to the right by increasing concentrations of DL 308-IT (1, 2, 4 and 10 p ~ ) . DL 308-IT appeared to be a weak competitive antagonist of histamine Hlreceptors on this preparation (PA, 5.6; slope function -0.92; pA,-pAlo 1.03). It has previously been reported that the contractile responses of the guinea-pig ileum to acetylcholine were antagonized in a non-competitive manner by DL 308-IT (Fosbraey et al 1980) in concentrations greater than 1 p ~ . The drug proved to be a powerful antagonist of the morphine-induced inhibition of the twitch response of the guinea-pig ileum to transmural electrical stimulation (0.2 Hz; 0.5 ms; 7-8 V). The antagonism did not appear to be competitive despite an apparent parallel displace ment of log dose-response curves with concentrations less than 8 p~ (Fig. 2). This property of DL 308-IT was also shared by metoclopramide (Fosbraey et al 1980). DL 308-IT in concentrations of 0.1-1.0 pM potentiated the twitch response of the guinea-pig ileum to transmural electrical stimulation, an effect that has