The recent report on Malignant Infantile Osteopetrosis
(MIOP) presenting with neonatal hypocalcaemia highlights the importance of
early recognition of a rare but treatable disorder.[1]
We would like to point out that recognition in the neonate is
difficult, as many of the characteristic manifestations have not had time
to develop. The normal sequence of events leading to the diagnosis being
ma...
The recent report on Malignant Infantile Osteopetrosis
(MIOP) presenting with neonatal hypocalcaemia highlights the importance of
early recognition of a rare but treatable disorder.[1]
We would like to point out that recognition in the neonate is
difficult, as many of the characteristic manifestations have not had time
to develop. The normal sequence of events leading to the diagnosis being
made is usually via a known family history or by radiologists commenting
on increased bone density, seen on x-ray.
In our experience of two related siblings, the mode of presentation,
in prematurity, was through a fracture of a long bone. This has not been
reported previously in the preterm neonate.
A suggested hypothesis is that the imbalance of osteoblast and
osteoclast function, which is represented in the article as leading to
hypocalcaemia, also leads to faulty and haphazard bone modelling, thus
making osteopetrotic bones prone to fractures.
ANIRBAN MAJUMDAR
Alder Hey Children’s Hospital
Liverpool, UK
NICK WILD
Warrington District General Hospital
Warrington, UK
Reference
(1) Srinivasan M, et al. Malignant infantile osteopetrosis presenting
with neonatal hypocalcaemia. Arch Dis Child Fetal Neonatal Ed 2000;83:F21-3.
Visveshwara's eLetter[1] emphasises that the results of the trigger trial should
not be interpreted as demonstrating lack of benefit for patient triggered
ventilation using other sensors or ventilators. I would concur with this
statement, which was emphasised in the paper.
However, Visveshwara should not be surprised to find different
outcome rates in the patients whose results he presents,...
Visveshwara's eLetter[1] emphasises that the results of the trigger trial should
not be interpreted as demonstrating lack of benefit for patient triggered
ventilation using other sensors or ventilators. I would concur with this
statement, which was emphasised in the paper.
However, Visveshwara should not be surprised to find different
outcome rates in the patients whose results he presents, as they are a
different group of infants from those reported in either study. The
evidence for benefit from the impedance technique is unconvincing, based
as it is on a controlled study of 40 infants and
a further 110 uncontrolled cases from one centre. A multicentre randomised
controlled trial of sufficient power is needed to demonstrate benefit from
the impedance and patient terminated ventilation techniques he describes.
To date such a study has not been performed.
Yadav's eLetter[2] suggests that important risk factors have not been compared in
the study. He describes two different types of risk factor, namely
inherent factors in the infant (intrauterine growth retardation) and
treatments applied to the infants (ventilation pressures, use of postnatal
steroids and of CPAP).
In a large randomised controlled study individual patients will have
varying degrees of risk for the outcomes being measured. The purpose of
the study design is to allocate patients in such a way that the overall
risk for each arm is the same. The larger the study, the less likely that
there will be an unequal balance of risk, assuming that the randomisation
process is performed correctly. We reported very similar birthweights and
gestations in the two groups. The proportion of growth retarded infants
was therefore allocated equally, and will not have biased the results.
A study comparing two modes of ventilation cannot be conducted with the
attendant clinicians blind to treatment allocation. The study protocol
required all other treatments to be applied equally to infants in both
arms of the study. There were written treatment protocols for each mode of
ventilation. However, it is still possible that other treatments could
have been applied unequally, with the possibility of bias resulting.
Interpretation of ventilator pressures is difficult, as in the
trigger ventilation technique weaning was undertaken at lower peak
inspiratory pressures. In Plymouth, trigger ventilated infants entered in the trial had slightly lower peak inspiratory pressures in the first 72 hours,
consistent with the different weaning policy. However, as the duration of
ventilation did not differ between the groups, it is reasonable to
conclude that there was no systematic bias in the application of
ventilation.
Information on the postnatal use of steroids was collected in the
trial. There was no difference in the proportion of infants receiving
postnatal steroids (25.5% vs 26.0%), nor in the postnatal age at which
they were first administered (median 15 vs 17 days). There is therefore no
evidence of bias resulting from their use.
The use of CPAP for weaning from ventilation has not been
demonstrated to reduce chronic lung disease in randomised controlled
trials. The paper Yadav cites discusses the possible benefits of a policy
of early use of nasal CPAP. This is not relevant to the trigger trial, as
infants recruited were by definition already being ventilated.
I would also like to qualify Yadav's statement that we found an increased
risk of pneumothorax in infants less than 28 weeks gestation. The
difference was not statistically significant, suggesting that the observed
difference may have occurred as a result of chance.
The trial therefore shows no evidence of bias, and the finding that
patient triggered ventilation has no additional benefit over intermittent
mandatory ventilation using the ventilators and techniques studied remains
valid. The trial cannot assist clinicians in their choice of other
modalities of support such as early use of CPAP or postnatal steroid use,
and is applicable both to growth retarded as well as appropriately grown
preterm infants.
Dr JH Baumer
on behalf of the trigger trial collaborators
References
(1) Visveshwara N. 'PTV': should it be patient triggered and patient terminated
ventilation? Arch Dis Child Fetal Neonatal Ed [Rapid Response] 27 June 2000
(2) Yadav M. To trigger or not to trigger? Arch Dis Child Fetal Neonatal Ed [Rapid Response] 5 July 2000
As highlighted in a recent edition of ADC Fetal and Neonatal edition,[1, 2] there is increasing concern about the
previously unreported high levels of neonatal group B
Streptococcal (GBS) infections in the UK. It is indeed
most important that we have national statistics for regional
variations in GBS infection, for it is only when we have
this information that we can begin to produce evidence based
guid...
As highlighted in a recent edition of ADC Fetal and Neonatal edition,[1, 2] there is increasing concern about the
previously unreported high levels of neonatal group B
Streptococcal (GBS) infections in the UK. It is indeed
most important that we have national statistics for regional
variations in GBS infection, for it is only when we have
this information that we can begin to produce evidence based
guidelines. It is however important that as well as
establishing the true incidence of GBS in the UK that we are
also clear about the data on which we base our
recommendations.
In the commentary following our paper entitled Neonatal
Group B Streptococcal Infection in South Bedfordshire[2]
Nicoll and Heath refer to the incidence at which a risk
factor based versus a screening approach to the prevention
of Group B Streptococcus would be cost effective, quoting
from a commentary by Isaacs.[3] The original article by
Mohle-Boetani et al[4] from which these data were derived,
actually gives figures of >0.65 and >1.45/1000 live births
at which a risk factor and screening based approach,
respectively would be cost effective. This contrasts with
those quoted by Isaacs,[3] and Nicoll and Heath[1] of 0.6
and >1.2/1000 live births.
More importantly it should be noted that these figures are
obtained from a study which used significantly different
criteria for both the definitions of a risk factor and on
the decision to treat. In the paper by Mohle-Boetani et al[4] the risk factor approach for treatment involved
treatment of both "teenagers or Blacks who developed labor
complications". The latter included either a temperature of
>37.5ºC or prolonged rupture of membranes (PROM) for >12
hours or preterm labor <_37 weeks="weeks" of="of" gestation.="gestation." this="this" is="is" obviously="obviously" a="a" quite="quite" different="different" population="population" from="from" those="those" defined="defined" in="in" the="the" cdc="cdc" guidelines5="guidelines5" where="where" all="all" mothers="mothers" who="who" go="go" into="into" preterm="preterm" labour="labour" _37="_37" gestation="gestation" or="or" have="have" prom="prom" _="_"/>18 hours)
or have a temperature (>38ºC) would be offered treatment
under a risk factor based strategy. The screening group in
the paper by Mohle-Boetani et al[4] were screened at 26-28
weeks gestation not 34-35 weeks as in the CDC guidelines,
the latter interval being considered to be when colonisation
status is most predictive of colonisation at delivery. Also
treatment was only given if the mothers also developed
intrapartum risk factors, (temperature >37.5º C or PROM >12
hours or preterm labor).
Mohle-Boetani et al conclude "The strategy we developed is
not generally applicable because different populations might
have different risk factors for delivery of infants with GBS
disease." In the study population 40% of births occurred in
women who were teenagers or Black.
It is important that before these figures become established
in the current literature we review the original data and
the premises on which it is based. It is important to pay
attention to crucial differences in the composition of
different populations and the risk factors employed in
different studies. As new guidelines are being developed we
should not make recommendations based on incorrect
information.
References
(1) Nicoll A, Heath P. Commentary. Arch Dis Child Fetal
Neonatal Ed 2000;82:F207.
(2) Beardsall K, Thompson MH, Mulla RJ. Neonatal Group B
streptococcal infection in South Bedfordshire, 1993-1998.
Arch Dis Child Fetal Neonatal Ed 2000;82:F205-7.
(3) Isaacs D. Prevention of early onset group B streptococcal
infection: screen, treat, or observe? Arch Dis Child Fetal
Neonatal Ed 1998;79:F81-2.
(4) Mohle-Boetani JC, Schuchat A, Plikaytis BD, Smith JD, Broome CV. Comparison of prevention strategies for neonatal
group B streptococcal infection. A population-based
economic analysis. JAMA 1993;270:1442-8.
(5) Centers for Disease Control. Prevention of perinatal
group B streptococcal disease: a public health perspective. MMWR May 31, 1996;45(RR-7):1-24.
I would like to mention two other modes of ventilation used during the immediate post extubation period. They deserve a mention in the excellent article on the current issues in weaning of preterm infants from assisted ventilation.[1] Nasopharyngeal-synchronised intermittent mandatory ventilation (NP-SIMV) and nasal synchronised intermittent positive pressure ventilation (nSIPPV) have been studied in two trials wi...
I would like to mention two other modes of ventilation used during the immediate post extubation period. They deserve a mention in the excellent article on the current issues in weaning of preterm infants from assisted ventilation.[1] Nasopharyngeal-synchronised intermittent mandatory ventilation (NP-SIMV) and nasal synchronised intermittent positive pressure ventilation (nSIPPV) have been studied in two trials with favourable results.
The first trial compared prospectively the incidence of respiratory failure in 41 VLBW infants randomised in immediate post extubation period to receive either NP-SIMV or nasopharyngeal continuous positive airway pressure (NCPAP).[2] The incidence of respiratory failure after extubation in NP-SIMV group was significantly lower than in the NCPAP group (5% vs 37% respectively; p=0.016). Few adverse effects were noted in the NP-SIMV mode namely one case of moderate abdominal distension and another of self resolving epistaxis. The authors had demonstrated in their pilot study[3] that they were able to avoid reintubation in 70% of the high risk newly extubated premature infants.
Another Study by Moretti et al[4] studied the gas exchange and respiratory effort during nasal synchronised intermittent positive pressure ventilation (nSIPPV) and nasal CPAP. The nSIPPV group demonstrated significant increased tidal volume, minute volume and decreased respiratory effort (p<_0.01 and="and" transcutaneous="transcutaneous" carbon="carbon" dioxide="dioxide" levels.="levels." the="the" authors="authors" concluded="concluded" that="that" nsippv="nsippv" may="may" provide="provide" more="more" ventilatory="ventilatory" support="support" than="than" ncpap="ncpap" in="in" post="post" extubation="extubation" period="period" with="with" less="less" patient="patient" inspiratory="inspiratory" effort.="effort." p="p"/>
Both are relatively non-invasive mode of ventilatory support during immediate post extubation period. There is a significant reduction in the reintubation rates (37% to 5%),[2] hence they appears an attractive mode to use in these high risk infants. Larger trials may be needed before the mode is universally accepted.
References
(1) Sinha SK, Donn S. Weaning from assisted ventilation: art or science? Arch Dis Child Fetal Neonatal Ed 2000;83:F64-70.
(2) Friedlich P, Lecart C, Posen R, Ramicone E, Chan L, Ramanathan R. A randomised trail of nasopharyngeal-synchronised intermittent mandatory ventilation versus nasopharyngeal continuous positive airway pressure in very low birth weight infants after extubation. J Perinatol 1999;19:413-18.
(3) Lecart C, Friedlich P, Ramanathan R, deLemos R. The combined use of intermittent mandatory ventilation (IMV) and nasopharyngeal CPAP (NP-CPAP) in premature infants following extubation. Pediatr Res 1997;41:258A.
(4) Moretti C, Gizzi C, Papoff P, Lampariello S, Capoferri M, Calcagnini G, Bucci G. Comparing the effects of nasal synchronised intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive pressure (nCPAP) after extubation in very low birth weight infants. Early Hum Dev 1999;56:167-77.
With great interest we read the paper by Whyte et al regarding the
practice of premedication before intubation in UK neonatal units.[1]
Their finding that only 37% of the units gave any sedation before
intubation is worrysome in view of the known physiologic responses to
awake intubation.[2-4] However, one potential bias in their study design
was not discussed.
With great interest we read the paper by Whyte et al regarding the
practice of premedication before intubation in UK neonatal units.[1]
Their finding that only 37% of the units gave any sedation before
intubation is worrysome in view of the known physiologic responses to
awake intubation.[2-4] However, one potential bias in their study design
was not discussed.
Since the information regarding this subject was
derived from telephonic interviews with the sister in charge of the unit
the results might merely reflect the policy of the unit as perceived by
this person and not the practice of the individual neonatologist
performing or supervising the intubation. Whether this would result in
underscoring or overscoring on the subject remains to be answered.
In our
experience sustantial interindividual variation exists among
neonatologists in the use of premedication before intubation of neonates.
In March of 1999 we performed a written survey among all neonatologists
and fellows working on each of the 10 neonatal intensive care units
(NICUs) in The Netherlands. The response rate was 77/87 (89%). Of the
respondents, 58 (76%) always gave some form of analgesia or sedation prior
to intubation, 13 (16%) only sometimes gave premedication, whereas 6 (8%)
never gave premedication. Of those who always gave premedication 33 (57%)
always combined the use of sedation with a muscle relaxant. Only 15 (17%)
used a written protocol for premedication.
Similar to Whyte’s results
great variation existed with regard to the choice and dose regimen of the
premedication. Morphine was the most widely used opioid, followed by
fentanyl and pethidine. Midazolam was the most popular sedative. On a few
occasions, ethomidate was mentioned as anaesthetic drug. Atropine was
sometimes used in patients with proven rapid onset of reflex bradycardia.
From these results it appears that premedication before intubation of
neonates is the rule rather than the exception in the NICU environment in
The Netherlands, although overscoring cannot be ruled out. When analysed
on a per NICU basis it was obvious that a great intra-NICU variation in
the practice of premedication exists.
Our results closely resemble those
of a recent survey among Canadian neonatologists which showed that in
approximately 75% of cases some premedication before intubation is used in
Canadian NICUs.[5] It would be interesting to see the results of a
survey among neonatologists in the UK.
The known physiological responses
to awake intubation include bradycardia, hypertension, hypoxemia,
laryngospasm and increased intracranial pressure (2-4). Moreover, awake
intubation requires more attempts, is more time-consuming and is
accompanied with more mucosal damage than premedicated intubation.[6]
Optimal prevention of these adverse effects probably requires the
combination of a vagolytic, an opioid and a muscle relaxant.[7]
Therefore, in our institution the combination of atropine (0.1 mg),
morphine (0.05-0.1 mg/kg) and vecuroniumbromide (0.05-0.1 mg/kg) is
routinely applied with great satisfaction. We fully agree with Whyte et al[1] that there is now sufficient evidence to support the routine practice
of premedication for elective intubation of neonates. Indeed, more
research is needed to investigate the optimal drug and dose regimen.
REFERENCES
1. Whyte S, Birrell G, Wyllie J: Premedication before intubation in
UK neonatal units. Arch Dis Child Fetal Neonatal Ed 2000;82:F38-F41.
2. Marshall TA, Deeder R, Pai S, Berkowitz GP, Austin TL: Physiologic
changes associated with endotracheal intubation in preterm infants. Crit
Care Med 1984; 12(6):501-3.
3. Kelly MA, Finer NN: Nasotracheal intubation in the neonate: Physiologic
responses and effects of atropine and pancuronium. J of Pediatrics
1984;105:303-9.
4. Friesen RH, Honda AT, Thieme RE: Changes in anterior fontanel pressure
in preterm neonates during tracheal intubation. Anesth Analg 1987;66:874-
8.
5. Vogel S, Gibbins S, Simmons B, Shah V: Premedication for endotracheal
intubation (EI) in neonates: A Canadian Perspective. Pediatric Research
2000;47(4):438A.
6. Oei J, Hari R, Lui K: Suxamethonium, atropine and morphine as induction
for neonatal nasotracheal intubation: A randomised controlled trial.
Pediatric Research 2000;47(4):421A.
7. Barrington KJ, Byrne PJ: Premedication for neonatal intubation. Am J of
Perinatol 1998;15(4):213-6.
Harry Molendijk, MD,
Neonatologist
Anneke Jaarsma, MD,
Neonatologist
Beatrix Children’s Hospital
Department of Pediatrics, Subdivision of Neonatology
University Hospital Groningen, P.O. Box 30001
9700 RB Groningen, The Netherlands
International randomised controlled trial by Dr Baumer[1] concluded that there was no benefit of patient triggered ventilation (PTV), but an added risk of increased pneumothorax in those less than 28 weeks gestation. In the same issue Beresford et al[2] concluded in a similar trial (with slightly more mature newborns 29 weeks vs 27), that PTV was feasible with no significant differences noted in medium term outcom...
International randomised controlled trial by Dr Baumer[1] concluded that there was no benefit of patient triggered ventilation (PTV), but an added risk of increased pneumothorax in those less than 28 weeks gestation. In the same issue Beresford et al[2] concluded in a similar trial (with slightly more mature newborns 29 weeks vs 27), that PTV was feasible with no significant differences noted in medium term outcomes.
Chronic lung disease (CLD) is multifactorial in origin and in Baumer’s trial significant factors, like ventilation pressures, intrauterine growth retardation, use of post natal steroids and nasal CPAP use, have been not compared between the groups.
Intrauterine growth retardation has been shown to be an important risk factor for CLD.[3]
In a trial where primary outcome is chronic lung disease omission of the data regarding use of post natal steroid use is quite surprising. Meta-analysis of the use of dexamethasone in VLBW infants has shown significant reduction in CLD at 36 weeks post conceptional age.[4]
The use of nasal continuous positive airway pressure (nasal CPAP) that has been shown to influence the incidence of CLD, 5 fails a mention in their trial. Breseford et al did not use nasal CPAP in any of their infants, but used synchronised intermittent mandatory ventilation (SIMV) in the weaning phase.
To the clinician, who has to make the choice of using these commonly available tools to reduce death and morbidity in this vulnerable group of infants, the choice is clear or more unclear? I leave the readers to decide.
References:
1. Baumer JH. International randomised controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed 2000;82:F5-F10.
2. Beresford MW, Shaw NJ, Manning D. Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome. Arch Dis Child Fetal Neonatl Ed 2000;82:F14-F18.
3.Korhonen P, Tammela O, Kovisto AM, Laippala AM, Ikonen S. Frequency and risk factors in bronchopulmonary dysplasia in a cohort of very low birth weight infants. Early Hum Dev 1999;54:245-58.
4. Bhuta T, Ohlsson A. Systematic review and meta-analysis of early postnatal dexamethasone for prevention of chronic lung disease. Arch Dis Child Fetal Neonatal Ed 1998;79:F26-33.
5. Josson B, Katz-Salamon M, Faxelius G, Broberger U, Lagercrantz H. Neonatal care of very low birthweight infants in special care units and neonatal intensive care units in Stockholm. Early nasal continuous positive airway pressure versus mechanical ventilation: gains and losses. Acta Paediatr Suppl 1997;419:4-10.
The article by Beardsall et al[1] once again raises awareness of this important and as yet unresolved issue for the UK. We would like to make two related points:
(1) Although the authors have discussed both early and late onset Group B Streptococcus disease, perinatal intervention is effective in
preventing only early onset Group B Streptococcus disease.
The article by Beardsall et al[1] once again raises awareness of this important and as yet unresolved issue for the UK. We would like to make two related points:
(1) Although the authors have discussed both early and late onset Group B Streptococcus disease, perinatal intervention is effective in
preventing only early onset Group B Streptococcus disease.
(2) A common related scenario is of a healthy newborn who is colonised with Group B streptococcus. Management strategies vary from no intervention to antibiotic prophylaxis (intramuscular Benzyl Penicillin
or oral Penicillin V or Amoxycillin) for 7 to 14 days. It would be useful
if the British Paediatric Surveillance Unit could gather data that would lead to evidence based guidelines
for management of these babies.
Reference
1. Beardsall K, Thompson MH, Mulla RJ. Neonatal group B
streptococcal infection in South Bedfordshire, 1993-1998. Arch Dis Child Fetal Neonatal Ed 2000;82:F205-7.
We were surprised at the results of the two studies published in your journal by Baumer[1] and Bersford et al[2]. Our experience with triggered ventilation over 10 years is shown in the table below:
We were surprised at the results of the two studies published in your journal by Baumer[1] and Bersford et al[2]. Our experience with triggered ventilation over 10 years is shown in the table below:
Complications of prematurity 1991-99
1991
1992
1993
1994
1995
1996
1997
1998
1999
<_1500 g="g" td="td"/>
n = 175
n = 190
n = 182
n = 184
n = 218
n = 169
n = 196
n = 203
n = 184
Retinopathy of prematurity Grade 3 or 4 (%)
2.2
5.2
6.5
4.8
5.5
7.1
3.2
Intraventricular haemorrhage Grade 3 or 4 (%)
13.1
2.5
16.4
12.3
12.8
11.8
7.6
9.3
3.2
Pneumothorax (%)
2.2
4.7
3.8
3.8
2.2
7
5
3.4
3.2
<_1250 g="g" td="td"/>
n = 130
n = 136
n = 133
n = 128
n = 162
n = 130
n = 154
n = 163
n = 134
Retinopathy of prematurity Grade 3 or 4 (%)
3
7.3
9
7
6.7
9.2
3.2
0.6
5.2
Intraventricular haemorrhage Grade 3 or 4 (%)
7.6
29.4
21
16.4
14.8
15.3
9.7
11.6
3.7
Pneumothorax (%)
3
4.4
5.2
4.6
3
5.3
3.5
3.6
3.7
In comparison to the outcome figures in the articles, our incidence of complications of pneumothoraces, intraventricular haemorrhage, and retinopathy of prematurity were significantly less.
As explained in our original article[3] and subsequently shown by others, pressure and flow triggered systems perform suboptimally in infants less than 1500 g. While bench testing may suggest an adequate response time, clinical practice indicates that these systems are compromised by the following:
(1) chest wall and lung compliance (2) airway resistance (3) leak around the endotracheal tube (4) endotracheal tube resistance (5) systems compliance.
The trigger delay may be aggravated by each of these factors, especially in the very low birth weight infants.
We believe that the inability of the patient to terminate the insufflation of gases at the onset of exhalation leads to increased intra thoracic pressure and even intra cranial pressure. Thus, if there is trigger delay as postulated above, the ventilator continues to force gases into the infant during the expiratory phase causing active exhalation and with consequent deleterious effects.
The system used in our unit is triggered by modified impedance technology. Peak detectors within the system detect onset of inspiration and exhalation with sensitivity and rapidly. Further, since the sensitivity depends on the rate of change of impedance, it is more sensitive when applied to very low birth weight infants or with increased rate of respiration. This may explain the marked difference in outcome, compared to the pressure triggered system, as shown by the application of the system in 1701 infants weighing less than 1500 g over 10 years. There were 1270 infants in the same group were less than 1250 g. The only problem we have encountered is that of some cardio respiratory monitors are incompatible with the triggering device. The signal processing through the monitors is crucial to the optimal performance of the respiratory analog input signal to the trigger/terminator. Prototypes of the system were used initially but since 1993 commercially available system (Sechrist SAVI) was utilized exclusively.
In large multicenter studies, derivation of consensus and consistent application of a standardized "conventional ventilation" protocol is very difficult. This may skew some of the outcome data. Perhaps the limitations of flow and pressure triggered systems need to be considered prior to abandoning triggered systems in the respiratory support of newborns. Active exhalation predisposes some of these infants to the complications cited. The incidence of ROP in our experience is less than that reported in the literature. Possibly the same mechanism described above also predisposes the infants to ROP.
Given all of the above, further studies and analysis may be prudent. Such studies of patient triggered ventilation should also incorporate the capability of patient terminated ventilation.
References
1. Baumer JH. International randomised controlled trial of patient triggered ventilation in neonatal respiratory distress syndrome. Arch Dis Child Fetal Neonatal Ed 2000;82:F5-F10.
2. Beresford MW, Shaw NJ, Manning D. Randomised controlled trial of patient triggered and conventional fast rate ventilation in neonatal respiratory distress syndrome. Arch. Dis Child Fetal Neonatal Ed 2000;82:F14-F18.
3. Visveshwara N, Freeman B, Peck M, Caliwag W, Shook S, Rajani K B. Patient-triggered synchronized assisted ventilation of newborns; report of a preliminary study and three years' experience. J Perinatol 1991;XI:347-354.
We read with interest the excellent review by Dr Ng on the fetal and neonatal hypothalamic-pituitary-adrenal axis.(1) Although the issue of antenatal administration of steroids is addressed in a separate section of the paper it is practically restricted to their antenatal use for the prevention of respiratory distress syndrome and other complications of prematurity.
We read with interest the excellent review by Dr Ng on the fetal and neonatal hypothalamic-pituitary-adrenal axis.(1) Although the issue of antenatal administration of steroids is addressed in a separate section of the paper it is practically restricted to their antenatal use for the prevention of respiratory distress syndrome and other complications of prematurity.
We would agree that this is the commonest reason for giving steroids antenatally. However albeit rare there are other indications for their administration during pregnancy for purely maternal reasons. An example is the mother who has undergone renal transplantation, where steroids may be given for prolonged periods.
Some 20 years ago we reported 5 babies (2),whose mothers being recipients of of renal transplants had received 10 mg/day of prednisone throughout pregnancy. Umbilical cord plasma cortisol levels ranged from 12.8 microgram/dl to 16.3 microgram/dl. Synachthen test yielded normal adrenal response in all but one where there was no rise of cortisol level at 30 and 60 minutes. This baby received a 10 day ACTH course following which a new Synachthen test yielded a normal resonse. We mention this experience to draw attention to other situations where adminstration of steroids may be rquired during pregnancy. We think that Dr Ng should have addressed these issues too.
References
1. Ng PC. The fetal and neonatal hypothalamic-pituitary-adrenal axis. Arch Dis Child Fetal Neonatal Ed 2000;82:F250-F254
2. Dellagrammaticas HD, Parkin JM. Maternal renal Transplantation-complications in the newborn baby. Paediatriki 1980;43:364-373
Dr HD Dellagrammaticas MD, FRCPCH
Dr Nicoletta Iacovidou MD
NICU, 2nd Department of Paediatrics University of Athens Aglaia Kyriakou Children's Hospital Athens, Greece
The interest displayed in the trigger ventilation trial by Burmester
and Petros is welcome.(1) Their letter raises questions about the
interpretation of the performance of the Dr�ger babylog 8000, which was
used in a minority of infants in the study.
The trigger sensor device is different, and I agree with their
implied statement that as each trigger ventilator performs differently
results obtained...
The interest displayed in the trigger ventilation trial by Burmester
and Petros is welcome.(1) Their letter raises questions about the
interpretation of the performance of the Dr�ger babylog 8000, which was
used in a minority of infants in the study.
The trigger sensor device is different, and I agree with their
implied statement that as each trigger ventilator performs differently
results obtained using one ventilator cannot be extrapolated to another
ventilator. However, both ventilators were used in PTV mode (sometimes
referred to as Synchronised Intermittent Positive Pressure Ventilation,
Assist Control or Synchronised Assisted Ventilation in Infants), with the
ventilator set to trigger at each inspiratory effort. No infants in this
study were ventilated with SIMV (Synchronised Intermittent Mandatory
Ventilation) where the baby's breaths, selected during a 'time window',
trigger the ventilator with the preset number of breaths per minute.
The results were reported in the way that they were for a reason. The
original study design allowed a four-way randomisation between the two
makes of ventilator and the two modes of ventilation. As was reported,
only three centres had enough of both ventilators to allow this to occur.
Other centres ventilating infants with the Dr�ger babylog had a two-way
randomisation between PTV and IMV.
Therefore the possibility of confounding by differences in practice
between centres needed to be excluded. If the centres using the Dr�ger as
well as the SLE ventilator had different outcomes from those using only
one make of ventilator, this might lead to inappropriate conclusions being
drawn if all infants being ventilated with one ventilator were simply
compared to those being ventilated with another. A logistic regression
model was therefore used to allow for possible centre effects (as well as
other significant factors such as gestation).
With that caveat, I have extracted the following numbers from the
database giving details of the crude observed rates of pneumothorax in the
infants less than 28 weeks, separately reported for the two makes of
ventilator.
PTV mode�
IMV mode
Dr�ger without pneumothorax
19
20
Dr�ger with pneumothorax
5 (20.8%)�
4 (16.7%)
SLE without pneumothorax
154
114
SLE with pneumothorax
35 (18.5%)�
14 (10.9%)
The observed rate of pneumothorax was substantially (but not
significantly, chi-squared 2.8, p>0.05<_0.1 higher="higher" in="in" the="the" infants="infants" ventilated="ventilated" ptv="ptv" mode="mode" than="than" imv="imv" using="using" sle="sle" _2000.="_2000." although="although" numbers="numbers" are="are" small="small" observed="observed" pneumothorax="pneumothorax" rate="rate" was="was" those="those" with="with" drger="drger" babylog="babylog" _8000="_8000" ventilator.="ventilator." it="it" therefore="therefore" seems="seems" somewhat="somewhat" illogical="illogical" to="to" recommend="recommend" caution="caution" _2000="_2000" less="less" _28="_28" weeks="weeks" gestation="gestation" but="but" not="not" extend="extend" this="this" ventilating="ventilating" _8000.="_8000." given="given" that="that" none="none" of="of" these="these" differences="differences" were="were" statistically="statistically" significant="significant" no="no" clear="clear" recommendation="recommendation" can="can" be="be" given.="given." is="is" why="why" wording="wording" used="used" publication="publication" might="might" prudent="prudent" avoid.="avoid." p="p"/> As regards the number of infants departing from their assigned mode
of ventilation, several points should be emphasised. The study protocol
permitted changing the mode of ventilation at the discretion of the
attending clinicians. This was inevitably interpreted differently by each
clinical team. Departure from the assigned mode of ventilation was not an
intended outcome, and it is evident that this occurred more commonly in
the more immature infants and those that subsequently died. High rates of
departure from the assigned mode cannot therefore readily be interpreted
as evidence of failure of the assigned mode. The numbers of infants of all
gestations departing from the assigned mode of ventilation are shown
below.
PTV
IMV
Drager not departing
35
40
Drager departing
16 (31.4%)
15 (27.3%)
SLE not departing
303
274
SLE departing
�107 (26.1%)
�47 (14.6%)
There was therefore a higher crude rate of departure from the
assigned mode of ventilation in infants ventilated with the Dr�ger babylog
8000, with a similar proportion transferred for failure to trigger.
It would be difficult to interpret the pneumothorax rates for those
infants who were actually being ventilated with their assigned mode of
ventilation. Some infants were switched to another mode of ventilation
after sustaining their pneumothorax. Most of the pneumothoraces occurred
whilst infants were receiving their assigned mode of ventilation, and this
included infants being trigger ventilated using the Dr�ger ventilator.
Burmester and Petros ask whether centres contributing few patients
might have higher morbidity rates, correcting for potential confounding
factors by using a logistic regression model. The pneumothorax rate from
centres contributing less than 20 patients was the same as the centres
contributing more infants.
We have used a model to identify outcome differences in infants
randomised within 3 months of the first infant being entered into the
study, correcting for individual centre effects, gestation, birthweight
and mode of ventilation. There was no significant difference in rates of
death and chronic lung disease, abnormal cranial ultrasound scan or
duration of ventilation. However, a marked and statistically significant
difference was found for pneumothorax rates. The 139 infants randomised
within 3 months had a pneumothorax rate of 5% versus a rate of 13% for
those randomised more than 3 months into the trial (odds ratio 0.30, 95%
confidence intervals 0.12 to 0.74, p=0.009). This was seen equally for
both modes of ventilation.
This finding suggests that the initial educational visit by the trial
co-ordinator had a beneficial effect on ventilator management that
disappeared as infants continued to be enrolled.
In summary, there is no evidence from this study of any trend towards
better outcomes with the Dr�ger babylog 8000 ventilator, though the small
numbers enrolled make any conclusions less robust. There is evidence that
suggests there may have been a short term reduction of pneumothorax rates
from the educational package offered at the start of the trial.
In conclusion, there was no convincing evidence of a beneficial
effect of a policy of using PTV in preterm infants with RDS with the
ventilators used. Regular attention to staff education on ventilator
techniques is recommended.
I would like to use this opportunity to pay tribute to the two trial
co-ordinators (Sue Ellis and Tom Mill), to the trial statistician (David
Wright) and to the data monitoring committee (David Field and Diana
Elbourne), whose details were inadvertently omitted from the final paper,
and without whom, together with the trial collaborators, the study would
not have been possible.
Dr Harry Baumer, on behalf of the trial collaborators
1. Burmester M, Petros A. Triggered ventilation in neonates. [Rapid Response] Arch Dis Child Fetal Neonatal Ed 9 May 2000
Dear Editor
The recent report on Malignant Infantile Osteopetrosis (MIOP) presenting with neonatal hypocalcaemia highlights the importance of early recognition of a rare but treatable disorder.[1]
We would like to point out that recognition in the neonate is difficult, as many of the characteristic manifestations have not had time to develop. The normal sequence of events leading to the diagnosis being ma...
Dear Editor
Visveshwara's eLetter[1] emphasises that the results of the trigger trial should not be interpreted as demonstrating lack of benefit for patient triggered ventilation using other sensors or ventilators. I would concur with this statement, which was emphasised in the paper.
However, Visveshwara should not be surprised to find different outcome rates in the patients whose results he presents,...
As highlighted in a recent edition of ADC Fetal and Neonatal edition,[1, 2] there is increasing concern about the previously unreported high levels of neonatal group B Streptococcal (GBS) infections in the UK. It is indeed most important that we have national statistics for regional variations in GBS infection, for it is only when we have this information that we can begin to produce evidence based guid...
I would like to mention two other modes of ventilation used during the immediate post extubation period. They deserve a mention in the excellent article on the current issues in weaning of preterm infants from assisted ventilation.[1] Nasopharyngeal-synchronised intermittent mandatory ventilation (NP-SIMV) and nasal synchronised intermittent positive pressure ventilation (nSIPPV) have been studied in two trials wi...
Dear Editor
With great interest we read the paper by Whyte et al regarding the practice of premedication before intubation in UK neonatal units.[1] Their finding that only 37% of the units gave any sedation before intubation is worrysome in view of the known physiologic responses to awake intubation.[2-4] However, one potential bias in their study design was not discussed.
Since the information regarding...
International randomised controlled trial by Dr Baumer[1] concluded that there was no benefit of patient triggered ventilation (PTV), but an added risk of increased pneumothorax in those less than 28 weeks gestation. In the same issue Beresford et al[2] concluded in a similar trial (with slightly more mature newborns 29 weeks vs 27), that PTV was feasible with no significant differences noted in medium term outcom...
The article by Beardsall et al[1] once again raises awareness of this important and as yet unresolved issue for the UK. We would like to make two related points:
(1) Although the authors have discussed both early and late onset Group B Streptococcus disease, perinatal intervention is effective in preventing only early onset Group B Streptococcus disease.
(2) A common related scenario...
We were surprised at the results of the two studies published in your journal by Baumer[1] and Bersford et al[2]. Our experience with triggered ventilation over 10 years is shown in the table below:
Complications of prematurity 1991-99
We read with interest the excellent review by Dr Ng on the fetal and neonatal hypothalamic-pituitary-adrenal axis.(1) Although the issue of antenatal administration of steroids is addressed in a separate section of the paper it is practically restricted to their antenatal use for the prevention of respiratory distress syndrome and other complications of prematurity.
We would agree that this is the commonest...
The interest displayed in the trigger ventilation trial by Burmester and Petros is welcome.(1) Their letter raises questions about the interpretation of the performance of the Dr�ger babylog 8000, which was used in a minority of infants in the study.
The trigger sensor device is different, and I agree with their implied statement that as each trigger ventilator performs differently results obtained...
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