The question of the safety of ibuprofen in lower respiratory tract infection(LRTI)(1) should be part of a bigger question. That question is the issue of the safety of ibuprofen in a child who is at risk of dehydration. A febrile child with LRTI is at risk of dehydration because of increased insensible fluid loss via the skin. Furthermore, in the presence of LRTI-related tachypnoea, there will be increased insensible fluid loss via the upper respiratory tract . These fluid losses are compounded when the child is too ill to maintain a good oral fluid intake.
In volume depleted states, such as the scenario depicted above, vasodilatory prostaglandins maintain adequate renal blood flow(RBF) and adequate glomerular filtration rate(GFR)(2). Nonsteroidal anti inflammatory drugs(NSAIDs) undermine those compensatory mechanisms by inhibiting prostaglandin synthesis(2). The consequence is the onset of NSAID-related acute kidney injury(AKI), as postulated by Misurac et al(3). These investigators postulated that NSAID-related inhibition of prostaglandin synthesis was the underlying cause of AKI in 21 of their 27 cases of NSAID-related AKI. In the remaining 6 children with AKI, acute interstitial nephritis(also attributable to NSAIDs) was the underlying cause.. Fifteen of the 20 children for whom dosing data were available took NSAID doses in the recommended range. Ibuprofen was the culprit NSAID in 67% of cases. Misurac et al also identified 54 other cases...
The question of the safety of ibuprofen in lower respiratory tract infection(LRTI)(1) should be part of a bigger question. That question is the issue of the safety of ibuprofen in a child who is at risk of dehydration. A febrile child with LRTI is at risk of dehydration because of increased insensible fluid loss via the skin. Furthermore, in the presence of LRTI-related tachypnoea, there will be increased insensible fluid loss via the upper respiratory tract . These fluid losses are compounded when the child is too ill to maintain a good oral fluid intake.
In volume depleted states, such as the scenario depicted above, vasodilatory prostaglandins maintain adequate renal blood flow(RBF) and adequate glomerular filtration rate(GFR)(2). Nonsteroidal anti inflammatory drugs(NSAIDs) undermine those compensatory mechanisms by inhibiting prostaglandin synthesis(2). The consequence is the onset of NSAID-related acute kidney injury(AKI), as postulated by Misurac et al(3). These investigators postulated that NSAID-related inhibition of prostaglandin synthesis was the underlying cause of AKI in 21 of their 27 cases of NSAID-related AKI. In the remaining 6 children with AKI, acute interstitial nephritis(also attributable to NSAIDs) was the underlying cause.. Fifteen of the 20 children for whom dosing data were available took NSAID doses in the recommended range. Ibuprofen was the culprit NSAID in 67% of cases. Misurac et al also identified 54 other cases of NSAID-related AKI in the medical literature during the period 1993 to 2009. Sixty percent of 50 cases for whom dosing data were available took the recommended does of NSAID. Fifty-three percent of the 54 cases were documented as having experienced reduced fluid intake before admission. Ibuprofen was the culprit NSAID in 20 of the 54 cases.
Comment
In the presence of LRTI-related dehydration ibuprofen has the potential to precipitate AKI as a result of NSAID-related inhibition of prostaglandin synthesis.
I have no funding and no conflict of interest
References
(1) Skehin K., Thompson A., Moriarty P
Is use of ibuprofen safe in children with signs and symptoms of lower respiratory tract infection?
Arch Dis Child 2019 Epub ahead of print
(2) Kim G-H
Renal effects of prostaglandins and cyclooxygenase-2 inhibitors
Electrolyte & Bood Disorders 2008;6:35-41
(3)Misurac JM., Knoderer CA., Leiser D et al
Nonsteroidal anti-inflammatory drugs are an important cause of acute kidney injury in children
J Pediatr 2013;162:1153-1159
Infant vitamin D supplementation prevents not just rickets but also hypocalcaemic seizures and cardiomyopathy (CMP). The BPSU survey (1) captures rickets incidence which, we feel compelled to highlight, represents only the tip of the iceberg of widespread vitamin D deficiency (VDD) in the population.
In the UK, child surveillance checks are led by general practitioners (GPs). Most GPs do not receive postgraduate paediatric training and have inadequate undergraduate paediatric exposure, as acknowledged by the RCPCH president: “by any stretch of the imagination, GP training in the UK in paediatrics is woefully inadequate” (2). Recognising rickets requires paediatric experience as exemplified by recent cases of VDD induced CMP- one child’s death was preceded by multiple unfruitful visits to GPs and casualty (3). As the BPSU survey reached out only to paediatricians and not GPs, the extent of underreporting and under diagnosis is likely huge, limiting comparison with countries where paediatricians oversee primary care. The conclusion that rickets incidence in the UK is lower than expected downplays the extent of the underlying public health crisis, particularly when a significant number of cases were excluded [table 2 of (1)]. The true disease burden is unravelled when family members of affected children are investigated (3).
Similar to previous studies, rickets incidence here is 90 to 166 fold higher in Asian and Black children compared to wh...
Infant vitamin D supplementation prevents not just rickets but also hypocalcaemic seizures and cardiomyopathy (CMP). The BPSU survey (1) captures rickets incidence which, we feel compelled to highlight, represents only the tip of the iceberg of widespread vitamin D deficiency (VDD) in the population.
In the UK, child surveillance checks are led by general practitioners (GPs). Most GPs do not receive postgraduate paediatric training and have inadequate undergraduate paediatric exposure, as acknowledged by the RCPCH president: “by any stretch of the imagination, GP training in the UK in paediatrics is woefully inadequate” (2). Recognising rickets requires paediatric experience as exemplified by recent cases of VDD induced CMP- one child’s death was preceded by multiple unfruitful visits to GPs and casualty (3). As the BPSU survey reached out only to paediatricians and not GPs, the extent of underreporting and under diagnosis is likely huge, limiting comparison with countries where paediatricians oversee primary care. The conclusion that rickets incidence in the UK is lower than expected downplays the extent of the underlying public health crisis, particularly when a significant number of cases were excluded [table 2 of (1)]. The true disease burden is unravelled when family members of affected children are investigated (3).
Similar to previous studies, rickets incidence here is 90 to 166 fold higher in Asian and Black children compared to white. As the proportion of ethnic minority in the UK continues to rise (14% in 2011 census) those at highest risk of VDD are failed most by inadequate prevention strategies (4).
Shockingly, 77% of reported cases were not on the Department of Health recommended vitamin D supplements demonstrating lack of policy implementation. Whilst we agree with the author’s recommendations on supplementation, vitamin D fortification of flour as a more cost-effective long term strategy should be seriously considered (5).
References:
1. Julies P, Lynn RM, Pall K, Leoni M, Calder A, Mughal Z, et al. Nutritional rickets under 16 years : UK surveillance results. Arch Dis Child. 2020;
2. Modi N, Simon C. Child health care: Adequate training for all UK GPs is long overdue. Br J Gen Pract. 2016;66(646):228–9.
3. Uday S, Fratzl-Zelman N, Roschger P, Klaushofer K, Chikermane A, Saraff V, et al. Cardiac, bone and growth plate manifestations in hypocalcemic infants: revealing the hidden body of the vitamin D deficiency iceberg. BMC Pediatr. 2018 Dec;18(1):183.
4. Uday S, Högler W. Prevention of rickets and osteomalacia in the UK: political action overdue. Arch Dis Child. 2018;103(9):901–6.
5. Aguiar M, Andronis L, Pallan M, Högler W, Frew E. The economic case for prevention of population vitamin D deficiency: a modelling study using data from England and Wales. Eur J Clin Nutr. 2019; DOI:10.1038/s41430-019-0486-x
We write in response to the article "Use of oral corticosteroids in the treatment of alopecia areata" by BJ Cowley and J Dong, published in January's edition of the journal.(1)
In this article, the authors present a summary of their literature search, concluding that oral corticosteroid pulse therapy may be a safe and effective treatment for sufferers of alopecia areata (AA). The authors highlight the risk of avascular necrosis of the hip with the use of corticosteroids, despite none of their cited studies reporting on this complication specifically.
We would argue that iatrogenic adrenal suppression (AS) secondary to exogenous corticosteroid administration is also a noteworthy risk in these patients. Symptomatic AS has been well documented in the asthmatic population receiving daily inhaled corticosteroids, occasionally resulting in adrenal crisis and even sadly death. Whilst there is a good level of awareness of AS amongst some colleagues using high doses of daily steroids, for example in the induction phases of leukaemia treatment, AS is not confined to these children and is as pertinent to those receiving pulsed steroids for AA(2,3).
In our centre we have had personal experience of looking after a child who required intubation and ventilation when they developed a viral illness and presented with hypotension and hypoglycaemia. They had received intralesional steroids to treat AA, which had caused severe adrenal sup...
We write in response to the article "Use of oral corticosteroids in the treatment of alopecia areata" by BJ Cowley and J Dong, published in January's edition of the journal.(1)
In this article, the authors present a summary of their literature search, concluding that oral corticosteroid pulse therapy may be a safe and effective treatment for sufferers of alopecia areata (AA). The authors highlight the risk of avascular necrosis of the hip with the use of corticosteroids, despite none of their cited studies reporting on this complication specifically.
We would argue that iatrogenic adrenal suppression (AS) secondary to exogenous corticosteroid administration is also a noteworthy risk in these patients. Symptomatic AS has been well documented in the asthmatic population receiving daily inhaled corticosteroids, occasionally resulting in adrenal crisis and even sadly death. Whilst there is a good level of awareness of AS amongst some colleagues using high doses of daily steroids, for example in the induction phases of leukaemia treatment, AS is not confined to these children and is as pertinent to those receiving pulsed steroids for AA(2,3).
In our centre we have had personal experience of looking after a child who required intubation and ventilation when they developed a viral illness and presented with hypotension and hypoglycaemia. They had received intralesional steroids to treat AA, which had caused severe adrenal suppression. This took a year to fully recover as evidenced by serial synacthen tests. They had no evidence of any primary adrenal pathology.
We therefore feel strongly that in this education-focused article, it is remiss not to highlight adrenal suppression as a key risk with any corticosteroid regimen.
Dr Elizabeth M Bayman, Dr Louise E Bath, Prof Amanda J Drake
1. Cowley BJ, Dong J. Use of oral corticosteroids in the treatment of alopecia areata. Archives of Disease in Childhood 2020;105:96-98.
2. Goldbloom EB, Mokashi A, Cummings EA, et al. Symptomatic adrenal suppression among children in Canada. Arch Dis Child. 2017 Apr;102(4):340-345.
3. Bayman EM, Drake AJ. Adrenal suppression, still a problem after all these years. Arch Dis Child. 2017 Apr;102(4):338-339.
I read with interest your recent publication “Language in 2-year-old children born preterm and term: a cohort study) in the Archives of Disease in Childhood. I have made certain observations, and would welcome your views on them.
I notice (Figure 1) that you screened 557 preterm infants for eligibility. Ninety three of these were excluded as they were deemed unsuitable by medical staff and another hundred and seventeen were excluded for other reasons. As those numbers are quite substantial, I am curious to know what those factors were, and think that some details on those factors will further enhance the quality of the paper.
Your preterm cohort is defined as <30 weeks gestation. The current evidence shows that mortality and morbidity in preterm babies is associated with degree of prematurity. Therefore, I am wondering that what was the distribution of gestational age in the group and was there any further subgroup analysis attempted.
You mentioned family history having an impact on the likelihood of language delay in the introduction. However, I note that this was not included in list of factors explored. I wonder if there was any particular reason to do so.
I look forward to hearing from you, and would like to thank you in anticipation for your time.
Many thanks,
Dr Anna Howells
Paediatric SPR
Community Paediatrics, Bromley
We enjoyed reading the study by Jaquet-Pilloud et al. 1 examining the role of nebulised 3% hypertonic saline (HS) and bronchiolitis. We thank the authors for this excellent pragmatic non-blinded, randomised controlled trial. Their conclusions support the UK evidence from the SABRE study 2 and their systematic review3 which provides evidence of the futility of adding hypertonic saline to the management of bronchiolitis when compared to standard care alone with length of stay (LOS) or ready for discharge as the primary outcome. The article was well written and easy to follow. The study examined 121 infants with bronchiolitis recruited over three years from one tertiary centre in Switzerland. We felt it illustrated the very important problem of underpowered studies concluding no differences between two treatment regimens. The authors used the Korppi et al 3 study to assume that the mean LOS for infants admitted to hospital with bronchiolitis was 5 days [120 hours] with a standard deviation of 1.2 days [28.8 hours]. Reduction in hospital stay by 1 day was considered clinically significant and based on this a minimum sample size of 120 (with 60 in each group) was arrived. However the data from this paper by Jaquet-Pilloud et al show that the mean LOS was 47 hours (± 8.5) for nebulised hypertonic saline group and 50.4 hours (±11) for standard care group. The LOS at the authors’ hospital was less than half of the assumption used for their power calculation....
We enjoyed reading the study by Jaquet-Pilloud et al. 1 examining the role of nebulised 3% hypertonic saline (HS) and bronchiolitis. We thank the authors for this excellent pragmatic non-blinded, randomised controlled trial. Their conclusions support the UK evidence from the SABRE study 2 and their systematic review3 which provides evidence of the futility of adding hypertonic saline to the management of bronchiolitis when compared to standard care alone with length of stay (LOS) or ready for discharge as the primary outcome. The article was well written and easy to follow. The study examined 121 infants with bronchiolitis recruited over three years from one tertiary centre in Switzerland. We felt it illustrated the very important problem of underpowered studies concluding no differences between two treatment regimens. The authors used the Korppi et al 3 study to assume that the mean LOS for infants admitted to hospital with bronchiolitis was 5 days [120 hours] with a standard deviation of 1.2 days [28.8 hours]. Reduction in hospital stay by 1 day was considered clinically significant and based on this a minimum sample size of 120 (with 60 in each group) was arrived. However the data from this paper by Jaquet-Pilloud et al show that the mean LOS was 47 hours (± 8.5) for nebulised hypertonic saline group and 50.4 hours (±11) for standard care group. The LOS at the authors’ hospital was less than half of the assumption used for their power calculation. Our calculation suggests that based on authors LOS, the minimum sample should be at least 240 subjects. This calculation was similar to the numbers recruited in the SABRE study which used the UK hospital episode statistics that suggested that the average (mean (SD)) time to discharge was 72 (32) hours to power their study and with three years of recruitment and a total of 317 infants in this study with 158 infants randomised to HS and 159 to standard care. There was no difference between the two arms in time to being declared fit for discharge. They showed the median (not mean in this paper) time to being declared fit for discharge was 76 hours from admission in each group, and the time to actual discharge was 89 hours in each group. Essentially Jaquet-Pilloud et al needed twice as many subjects to be sure that there was no type 2 error and to be confident about the accuracy of their conclusions.
Yours sincerely
Dr Muthukumar Sakthivel, Dr Dure Yasrab, Dr Kevin Enright and Professor Colin Powell
Pediatric Emergency Department Sidra Medicine, Doha, Qatar
Dr Whitaker, in a letter in response to our Archimedes review of whether waveform capnography reliably approximates paCO2 in neonates, highlights two important questions which capnography seeks to address: Firstly, whether or not the endotracheal tube (ETT) is patent and correctly positioned in the trachea and secondly, whether the current ventilation strategy provides optimal CO2 clearance for the patient. The two questions are, of course, interlinked.
To date, in our field of neonatal medicine, the ETCO2 provides a valuable adjunct to clinical examination in determining ETT position and patency both at the point of intubation and during ongoing mechanical ventilation. However, for reasons explained in the paper, the numerical approximations to alveolar pCO2 provided by the currently available techniques of wave form capnography in neonates are not accurate enough to guide ventilatory changes. Thus, to guide ventilator changes, many neonatal intensive care units currently use transcutaneous capnometry.
In addition to the physiological properties, the waveform capnography sensors add extra weight and dead space to an infant’s ventilator circuit. This adds further complexity, like their still not fully assessed effect on volume-guarantee ventilation and potential for auto-triggering of ventilators. As volume guarantee is now considered the gold standard for ventilating preterm infants with respiratory distress syndrome, the value of waveform capnography, in addi...
Dr Whitaker, in a letter in response to our Archimedes review of whether waveform capnography reliably approximates paCO2 in neonates, highlights two important questions which capnography seeks to address: Firstly, whether or not the endotracheal tube (ETT) is patent and correctly positioned in the trachea and secondly, whether the current ventilation strategy provides optimal CO2 clearance for the patient. The two questions are, of course, interlinked.
To date, in our field of neonatal medicine, the ETCO2 provides a valuable adjunct to clinical examination in determining ETT position and patency both at the point of intubation and during ongoing mechanical ventilation. However, for reasons explained in the paper, the numerical approximations to alveolar pCO2 provided by the currently available techniques of wave form capnography in neonates are not accurate enough to guide ventilatory changes. Thus, to guide ventilator changes, many neonatal intensive care units currently use transcutaneous capnometry.
In addition to the physiological properties, the waveform capnography sensors add extra weight and dead space to an infant’s ventilator circuit. This adds further complexity, like their still not fully assessed effect on volume-guarantee ventilation and potential for auto-triggering of ventilators. As volume guarantee is now considered the gold standard for ventilating preterm infants with respiratory distress syndrome, the value of waveform capnography, in addition to standard expiratory tidal volume monitoring on volume-guarantee ventilated infants and transcutaneous capnometry, is a topic worthy of further research and discussion.
Dear Editor
We read with interest Dr Scrivens et al’s commentary [1]. The mother’s question - ‘should capnography be used for breathing tube monitoring?’ – captures the subject addressed in our ‘PICNIC survey’ [2]. Conversely, the authors examine a completely different question - ‘is capnography an optimum respiratory monitor in ventilated neonates?’
A respiratory monitor detects whether the end-tidal CO2 value usefully measures pulmonary ventilation or PaCO2. Although not our focus here, we are surprised the review omitted Kugelman’s study which reported waveform capnography monitoring in neonatal ICU (NICU) improved ventilation accuracy and neurological outcomes [3].
An airway monitor assesses ‘whether lung ventilation is taking place via a tracheal tube that is in the airway and is patent’. High rates of neonatal failed intubation, oesophageal intubation, accidental extubation and reports of associated patient harm all suggest the value of a reliable airway monitor in NICU. Waveform capnography rapidly detects correct intubation with few false positives and immediately detects displacement or disconnection, the evidence for which we have previously set out [4-6].
Some neonatologists argue that continuous waveform capnography cannot be used in neonates. It is used routinely in neonatal anaesthesia. Others use it routinely during transfer of small neonates (eg 400g) (personal communication Dr James Tooley, Consultant, Bristol) sometimes only for it...
Dear Editor
We read with interest Dr Scrivens et al’s commentary [1]. The mother’s question - ‘should capnography be used for breathing tube monitoring?’ – captures the subject addressed in our ‘PICNIC survey’ [2]. Conversely, the authors examine a completely different question - ‘is capnography an optimum respiratory monitor in ventilated neonates?’
A respiratory monitor detects whether the end-tidal CO2 value usefully measures pulmonary ventilation or PaCO2. Although not our focus here, we are surprised the review omitted Kugelman’s study which reported waveform capnography monitoring in neonatal ICU (NICU) improved ventilation accuracy and neurological outcomes [3].
An airway monitor assesses ‘whether lung ventilation is taking place via a tracheal tube that is in the airway and is patent’. High rates of neonatal failed intubation, oesophageal intubation, accidental extubation and reports of associated patient harm all suggest the value of a reliable airway monitor in NICU. Waveform capnography rapidly detects correct intubation with few false positives and immediately detects displacement or disconnection, the evidence for which we have previously set out [4-6].
Some neonatologists argue that continuous waveform capnography cannot be used in neonates. It is used routinely in neonatal anaesthesia. Others use it routinely during transfer of small neonates (eg 400g) (personal communication Dr James Tooley, Consultant, Bristol) sometimes only for it to be removed on arrival at NICU! In veterinary practice it may be used in animals weighing 50g (personal communication, Dr Jonathan Cracknell, Wildlife Anaesthesia Services, Longleat, Wiltshire).
Proving the value of safety measures by randomised controlled trials (RCTs) is often impractical because of the rarity of the adverse outcomes the intervention is intended to prevent (here hypoxaemic brain injury or death). There are no RCTs that show outcome benefit of oximetry in anaesthesia or critical care, but its use is universal. Proving capnography improves outcomes via RCT may be challenging – though studying the impact on prompt recognition of incorrect intubation, disconnections and accidental extubation is feasible.
In 2011 waveform capnography was available in half of adult ICUs and these often used it infrequently [7]. There was significant resistance to the NAP4 recommendation for universal implementation, including senior intensivists stating its use was impossible and unnecessary - because ventilator parameters would readily identify problems. That some adult ICUs were using it widely and others not at all mirrors current NICU practice: this variation in practice merits urgent investigation and explanation. Four years after NAP4, 98% of adult ICUs had waveform capnography, using it routinely at intubation and for monitoring all ventilated patients [8]. Capnography in ICU is practical and it is now accepted in UK adult ICUs as a standard of care.
Neonates, in common with all humans, exhale carbon dioxide with every breath. Detection of this has the potential to be the most rapid and reliable monitor of airway integrity in neonates reliant on an artificial airway. In determining whether waveform capnography is the right tool in their setting it is important that the neonatal community start to ask the right question.
TM Cook
KE Foy
FE Kelly
References
1. Scrivens A, Zivanovic S, Roehr CC. Is waveform capnography reliable in neonates? Arch Dis Child July 2019 Vol 104 No 7 http://dx.doi.org/10.1136/archdischild-2018-316577
2. Foy K, Mew E, Cook T, et al United Kingdom paediatric and neonatal intensive care airway management: the PICNIC survey, Anaesthesia 2018; 73: 1337-44
3. Kugelman A, Golan A, Riskin A et al. Impact of Continuous Capnography in Ventilated Neonates: A Randomized, Multicenter Study. Journal of Pediatrics 2016; 168: 56-61
4. Cook TM, Foy K, Kelly F. Paediatric intensive care and neonatal intensive care airway management in the United Kingdom: the PIC-NIC survey. (Response to Mactier et al.) http://www.respond2articles.com/ANA/forums/thread/2670.aspx
5. Cook TM, Foy K, Kelly F. Paediatric intensive care and neonatal intensive care airway management in the United Kingdom: the PIC-NIC survey. (Response to Wyllie et al.) http://www.respond2articles.com/ANA/forums/thread/2677.aspx
6. Cook TM, Foy K, Kelly F. Paediatric intensive care and neonatal intensive care airway management in the United Kingdom: the PIC-NIC survey. Anaesthesia 2019; 74; 118-120
7. Cook TM, Woodall N, Harper J, Benger J. Major complications of airway management in the UK: results of the 4th National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 2 Intensive Care and Emergency Department. British Journal of Anaesthesia 2011; 106: 632-42
8. Cook TM, Woodall N, Frerk C. A national survey of the impact of NAP4 on airway management practice in United Kingdom hospitals: closing the safety gap in anaesthesia, intensive care and the emergency department. British Journal of Anaesthesia 2016; 117: 182-190
Dear authors,
I read with great interest your article on multiple café-au-lait macules and movement disorder (1). I want to point out that probably an error happened during formatting of table 1. The term RASopathies is used to refer to a group of diseases caused by a mutation in a gene coding for a key component of the RAS-pathway and resulting in hyperactivation of the pathway. This group commonly includes Noonan syndrome, Neurofibromatosis type 1, Legius syndrome, LEOPARD syndrome (now referred to as Noonan syndrome with multiple lentigines), Costello syndrome, CFC syndrome, hereditary gingival fibromatosis, capillary malformation-arteriovenous malformation and Loh syndrome (2). It is confusing to find RASopathies next to Noonan, Legius and LEOPARD syndrome in the same column of table 1. In the same column Legius syndrome is listed as well as NF-like syndrome. Legius syndrome is listed followed by (PTPN11) and NF-like syndrome is followed by the gene (SPRED1). PTPN11 should be listed after Noonan syndrome because it is the most frequent cause of Noonan syndrome and it is not related to Legius syndrome. Legius syndrome is the same as NF1-like syndrome and only one of the two should be listed followed by (SPRED1). In our first publication (3) we named the condition neurofibromatosis 1-like syndrome but later is was renamed Legius syndrome (4).
Congenital mismatch repair deficiency (CMMRD) is another autosomal recessive condition with café-au-lait macules and...
Dear authors,
I read with great interest your article on multiple café-au-lait macules and movement disorder (1). I want to point out that probably an error happened during formatting of table 1. The term RASopathies is used to refer to a group of diseases caused by a mutation in a gene coding for a key component of the RAS-pathway and resulting in hyperactivation of the pathway. This group commonly includes Noonan syndrome, Neurofibromatosis type 1, Legius syndrome, LEOPARD syndrome (now referred to as Noonan syndrome with multiple lentigines), Costello syndrome, CFC syndrome, hereditary gingival fibromatosis, capillary malformation-arteriovenous malformation and Loh syndrome (2). It is confusing to find RASopathies next to Noonan, Legius and LEOPARD syndrome in the same column of table 1. In the same column Legius syndrome is listed as well as NF-like syndrome. Legius syndrome is listed followed by (PTPN11) and NF-like syndrome is followed by the gene (SPRED1). PTPN11 should be listed after Noonan syndrome because it is the most frequent cause of Noonan syndrome and it is not related to Legius syndrome. Legius syndrome is the same as NF1-like syndrome and only one of the two should be listed followed by (SPRED1). In our first publication (3) we named the condition neurofibromatosis 1-like syndrome but later is was renamed Legius syndrome (4).
Congenital mismatch repair deficiency (CMMRD) is another autosomal recessive condition with café-au-lait macules and similar to ataxia telangiectasia it is important to recognize because it is associated with malignancies (5). I suggest to add CMMRD to table 1.
References
1 Madaan P, Mukherjee S, Reddy C, et al. Multiple café-au-lait macules and movement disorder: think beyond neurofibromatosis. Arch Dis Child 2019;0:1. doi:10.1136/archdischild-2019-317497
2 Aoki Y, Niihori T, Inoue S, Matsubara Y. Recent advances in RASopathies. J Hum Genet 2016 ;61:33-9.
3 Brems H, Chmara M, Sahbatou M,et al. Germline loss-of-function mutations in SPRED1 cause a neurofibromatosis 1-like phenotype. Nat Genet 2007; 39:1120-26.
4 Stevenson D, Viskochil D Pigmentary findings in neurofibromatosis type 1-like syndrome (Legius syndrome): potential diagnostic dilemmas. JAMA 2009;19:2150-1.
5 Suerink M, Ripperger T, Messiaen L et al. Constitutional mismatch repair deficiency as a differential diagnosis of neurofibromatosis type 1: consensus guidelines for testing a child without malignancy. J Med Genet 2019;56:53-62.
I was interested to read the Archimedes article reviewing the structured question ‘in neonates who require ventilation, does waveform capnography give an accurate approximation of PaCO2?’ The findings such as the accuracy of ETCO2 decreases with the severity of lung disease (Grade B) adds to similar knowledge about waveform capnography when it was introduced in adults.
Whenever capnography is discussed however it should always be remembered that the primary reason for its introduction into clinical practice was to reliably ensure patients oxygenation and reduce the incidence of hypoxic brain damage, which it did so dramatically. The presence of a capnography waveform is the gold standard to demonstrate the integrity and correct position of an airway and establish that the patient is being ventilated with the intended oxygen. This eureka moment discovering that waveform capnography is more about oxygenation than accuracy of PaCO2 estimation is crucial for patient safety. The exact value of PaCO2 is secondary.
Unfortunately for over 20 years adult intensive care missed this eureka moment and consequently never started to use waveform capnography in adult ITUs when it was being universally introduced into operating theatres in the late 1980s [1].
Despite waveform capnography continuing to save many patients lives in operating theatres the argument that the accuracy of ETCO2 decreased with the severity of lung disease predominated in intensive care and w...
I was interested to read the Archimedes article reviewing the structured question ‘in neonates who require ventilation, does waveform capnography give an accurate approximation of PaCO2?’ The findings such as the accuracy of ETCO2 decreases with the severity of lung disease (Grade B) adds to similar knowledge about waveform capnography when it was introduced in adults.
Whenever capnography is discussed however it should always be remembered that the primary reason for its introduction into clinical practice was to reliably ensure patients oxygenation and reduce the incidence of hypoxic brain damage, which it did so dramatically. The presence of a capnography waveform is the gold standard to demonstrate the integrity and correct position of an airway and establish that the patient is being ventilated with the intended oxygen. This eureka moment discovering that waveform capnography is more about oxygenation than accuracy of PaCO2 estimation is crucial for patient safety. The exact value of PaCO2 is secondary.
Unfortunately for over 20 years adult intensive care missed this eureka moment and consequently never started to use waveform capnography in adult ITUs when it was being universally introduced into operating theatres in the late 1980s [1].
Despite waveform capnography continuing to save many patients lives in operating theatres the argument that the accuracy of ETCO2 decreased with the severity of lung disease predominated in intensive care and was repeatedly used to justify it never being used there.
Subsequently a minimum of 150 patients probably died from major airway complications because the routine use of continuous waveform capnography in ITUs in the UK was not widely recommended until 2011 when NAP4 was published [2] and changed practice [3].
It would be very sad if this article’s findings were similarly interpreted by others to justify not routinely using lifesaving waveform capnography monitoring when ventilating neonates.
Airway deaths are particularly devastating [4] and I can only hope that for everyone's sake, the babies, their families and any staff 2nd victims history will not continue to repeat itself in neonatal intensive care [5].
David K Whitaker
David K Whitaker FRCA, FFPMRCA, FFICM, Hon FCARCSI
Consultant in Anaesthesia and Intensive care Manchester Royal Infirmary
References
1. Whitaker DK. Time for capnography - everywhere. Anaesthesia. 2011; 66: 544-9.
2. Cook TM, Woodall N, Harper J, Benger J. Major complications of airway management in the UK: results of the 4th National Audit Project of the Royal College of Anaesthetists and the Difficult Airway Society. Part 2 Intensive Care and Emergency Department. British Journal of Anaesthesia 2011; 106: 632-42
3. Cook TM. Airway complications – strategies for prevention. Anaesthesia 2018; 73: 93-111.
4. Baby’s family in call for action over ‘neglect’ finding in inquest https://www.yorkshirepost.co.uk/news/latest-news/baby-s-family-in-call-f... (accessed 07 July 2019)
5. Pathan N. British Broadcasting Corporation. Sick babies at risk from lack of breathing tube monitoring. https://www.bbc.co.uk/news/health-45197375 (accessed 07 July 2019)
Conflict of Interest
DKW is currently Chairman of the Patient Safety Committee of the European Board of Anaesthesiology. He has received lecture fees from Aguettant Ltd and Medtronic, all donated to Lifebox and travel expenses for the Global Capnography Project (GCAP) in Malawi from Medtronic.
We welcome the comments made by Professor Andrew Williams, who has been a great supporter of our UK-wide study of children with progressive intellectual and neurological deterioration (PIND). The PIND Study uses the mechanism provided by the British Paediatric Surveillance Unit (BPSU), which is based in the Royal College of Paediatrics and Child Health. Since 1986 the BPSU has provided paediatricians in the United Kingdom with the means of investigating rare disorders of childhood. As Professor Williams points out there is a need to make research central to good paediatric practice and the BPSU continues to facilitate that.
The PIND Study is funded by the National Institute for Health Research (NIHR) Policy Research Programme to look for cases of variant Creutzfeldt-Jakob disease (vCJD) among the many neurodegenerative diseases of childhood. Since the PIND Study started in 1997 we have identified children with more than 190 of these rare disorders - that number constantly increases as new diseases and new genetic variants of known diseases are discovered. Thus our study not only provides the sole means of systematically searching for vCJD in children but also gives a unique oversight of the changing pattern of childhood neurodegenerative disease in the UK. We work closely with the National Creutzfeldt-Jakob Disease Research and Surveillance Unit which carries out surveillance for vCJD in adults.
Professor Williams highlights the fact that our work could not be...
We welcome the comments made by Professor Andrew Williams, who has been a great supporter of our UK-wide study of children with progressive intellectual and neurological deterioration (PIND). The PIND Study uses the mechanism provided by the British Paediatric Surveillance Unit (BPSU), which is based in the Royal College of Paediatrics and Child Health. Since 1986 the BPSU has provided paediatricians in the United Kingdom with the means of investigating rare disorders of childhood. As Professor Williams points out there is a need to make research central to good paediatric practice and the BPSU continues to facilitate that.
The PIND Study is funded by the National Institute for Health Research (NIHR) Policy Research Programme to look for cases of variant Creutzfeldt-Jakob disease (vCJD) among the many neurodegenerative diseases of childhood. Since the PIND Study started in 1997 we have identified children with more than 190 of these rare disorders - that number constantly increases as new diseases and new genetic variants of known diseases are discovered. Thus our study not only provides the sole means of systematically searching for vCJD in children but also gives a unique oversight of the changing pattern of childhood neurodegenerative disease in the UK. We work closely with the National Creutzfeldt-Jakob Disease Research and Surveillance Unit which carries out surveillance for vCJD in adults.
Professor Williams highlights the fact that our work could not be carried out without the active support and involvement of the paediatricians who report cases to our study (and all the other studies that are carried out via the BPSU system). By giving their time in this way individual paediatricians become an active part of a highly successful national epidemiological surveillance system and their contribution should be acknowledged – many thanks to them all.
The question of the safety of ibuprofen in lower respiratory tract infection(LRTI)(1) should be part of a bigger question. That question is the issue of the safety of ibuprofen in a child who is at risk of dehydration. A febrile child with LRTI is at risk of dehydration because of increased insensible fluid loss via the skin. Furthermore, in the presence of LRTI-related tachypnoea, there will be increased insensible fluid loss via the upper respiratory tract . These fluid losses are compounded when the child is too ill to maintain a good oral fluid intake.
Show MoreIn volume depleted states, such as the scenario depicted above, vasodilatory prostaglandins maintain adequate renal blood flow(RBF) and adequate glomerular filtration rate(GFR)(2). Nonsteroidal anti inflammatory drugs(NSAIDs) undermine those compensatory mechanisms by inhibiting prostaglandin synthesis(2). The consequence is the onset of NSAID-related acute kidney injury(AKI), as postulated by Misurac et al(3). These investigators postulated that NSAID-related inhibition of prostaglandin synthesis was the underlying cause of AKI in 21 of their 27 cases of NSAID-related AKI. In the remaining 6 children with AKI, acute interstitial nephritis(also attributable to NSAIDs) was the underlying cause.. Fifteen of the 20 children for whom dosing data were available took NSAID doses in the recommended range. Ibuprofen was the culprit NSAID in 67% of cases. Misurac et al also identified 54 other cases...
Dear Editor
Infant vitamin D supplementation prevents not just rickets but also hypocalcaemic seizures and cardiomyopathy (CMP). The BPSU survey (1) captures rickets incidence which, we feel compelled to highlight, represents only the tip of the iceberg of widespread vitamin D deficiency (VDD) in the population.
In the UK, child surveillance checks are led by general practitioners (GPs). Most GPs do not receive postgraduate paediatric training and have inadequate undergraduate paediatric exposure, as acknowledged by the RCPCH president: “by any stretch of the imagination, GP training in the UK in paediatrics is woefully inadequate” (2). Recognising rickets requires paediatric experience as exemplified by recent cases of VDD induced CMP- one child’s death was preceded by multiple unfruitful visits to GPs and casualty (3). As the BPSU survey reached out only to paediatricians and not GPs, the extent of underreporting and under diagnosis is likely huge, limiting comparison with countries where paediatricians oversee primary care. The conclusion that rickets incidence in the UK is lower than expected downplays the extent of the underlying public health crisis, particularly when a significant number of cases were excluded [table 2 of (1)]. The true disease burden is unravelled when family members of affected children are investigated (3).
Similar to previous studies, rickets incidence here is 90 to 166 fold higher in Asian and Black children compared to wh...
Show MoreDear editor
We write in response to the article "Use of oral corticosteroids in the treatment of alopecia areata" by BJ Cowley and J Dong, published in January's edition of the journal.(1)
In this article, the authors present a summary of their literature search, concluding that oral corticosteroid pulse therapy may be a safe and effective treatment for sufferers of alopecia areata (AA). The authors highlight the risk of avascular necrosis of the hip with the use of corticosteroids, despite none of their cited studies reporting on this complication specifically.
We would argue that iatrogenic adrenal suppression (AS) secondary to exogenous corticosteroid administration is also a noteworthy risk in these patients. Symptomatic AS has been well documented in the asthmatic population receiving daily inhaled corticosteroids, occasionally resulting in adrenal crisis and even sadly death. Whilst there is a good level of awareness of AS amongst some colleagues using high doses of daily steroids, for example in the induction phases of leukaemia treatment, AS is not confined to these children and is as pertinent to those receiving pulsed steroids for AA(2,3).
In our centre we have had personal experience of looking after a child who required intubation and ventilation when they developed a viral illness and presented with hypotension and hypoglycaemia. They had received intralesional steroids to treat AA, which had caused severe adrenal sup...
Show MoreDear Sanchez et al,
I read with interest your recent publication “Language in 2-year-old children born preterm and term: a cohort study) in the Archives of Disease in Childhood. I have made certain observations, and would welcome your views on them.
I notice (Figure 1) that you screened 557 preterm infants for eligibility. Ninety three of these were excluded as they were deemed unsuitable by medical staff and another hundred and seventeen were excluded for other reasons. As those numbers are quite substantial, I am curious to know what those factors were, and think that some details on those factors will further enhance the quality of the paper.
Your preterm cohort is defined as <30 weeks gestation. The current evidence shows that mortality and morbidity in preterm babies is associated with degree of prematurity. Therefore, I am wondering that what was the distribution of gestational age in the group and was there any further subgroup analysis attempted.
You mentioned family history having an impact on the likelihood of language delay in the introduction. However, I note that this was not included in list of factors explored. I wonder if there was any particular reason to do so.
I look forward to hearing from you, and would like to thank you in anticipation for your time.
Many thanks,
Dr Anna Howells
Paediatric SPR
Community Paediatrics, Bromley
Dear Editor
We enjoyed reading the study by Jaquet-Pilloud et al. 1 examining the role of nebulised 3% hypertonic saline (HS) and bronchiolitis. We thank the authors for this excellent pragmatic non-blinded, randomised controlled trial. Their conclusions support the UK evidence from the SABRE study 2 and their systematic review3 which provides evidence of the futility of adding hypertonic saline to the management of bronchiolitis when compared to standard care alone with length of stay (LOS) or ready for discharge as the primary outcome. The article was well written and easy to follow. The study examined 121 infants with bronchiolitis recruited over three years from one tertiary centre in Switzerland. We felt it illustrated the very important problem of underpowered studies concluding no differences between two treatment regimens. The authors used the Korppi et al 3 study to assume that the mean LOS for infants admitted to hospital with bronchiolitis was 5 days [120 hours] with a standard deviation of 1.2 days [28.8 hours]. Reduction in hospital stay by 1 day was considered clinically significant and based on this a minimum sample size of 120 (with 60 in each group) was arrived. However the data from this paper by Jaquet-Pilloud et al show that the mean LOS was 47 hours (± 8.5) for nebulised hypertonic saline group and 50.4 hours (±11) for standard care group. The LOS at the authors’ hospital was less than half of the assumption used for their power calculation....
Show MoreDr Whitaker, in a letter in response to our Archimedes review of whether waveform capnography reliably approximates paCO2 in neonates, highlights two important questions which capnography seeks to address: Firstly, whether or not the endotracheal tube (ETT) is patent and correctly positioned in the trachea and secondly, whether the current ventilation strategy provides optimal CO2 clearance for the patient. The two questions are, of course, interlinked.
Show MoreTo date, in our field of neonatal medicine, the ETCO2 provides a valuable adjunct to clinical examination in determining ETT position and patency both at the point of intubation and during ongoing mechanical ventilation. However, for reasons explained in the paper, the numerical approximations to alveolar pCO2 provided by the currently available techniques of wave form capnography in neonates are not accurate enough to guide ventilatory changes. Thus, to guide ventilator changes, many neonatal intensive care units currently use transcutaneous capnometry.
In addition to the physiological properties, the waveform capnography sensors add extra weight and dead space to an infant’s ventilator circuit. This adds further complexity, like their still not fully assessed effect on volume-guarantee ventilation and potential for auto-triggering of ventilators. As volume guarantee is now considered the gold standard for ventilating preterm infants with respiratory distress syndrome, the value of waveform capnography, in addi...
Dear Editor
Show MoreWe read with interest Dr Scrivens et al’s commentary [1]. The mother’s question - ‘should capnography be used for breathing tube monitoring?’ – captures the subject addressed in our ‘PICNIC survey’ [2]. Conversely, the authors examine a completely different question - ‘is capnography an optimum respiratory monitor in ventilated neonates?’
A respiratory monitor detects whether the end-tidal CO2 value usefully measures pulmonary ventilation or PaCO2. Although not our focus here, we are surprised the review omitted Kugelman’s study which reported waveform capnography monitoring in neonatal ICU (NICU) improved ventilation accuracy and neurological outcomes [3].
An airway monitor assesses ‘whether lung ventilation is taking place via a tracheal tube that is in the airway and is patent’. High rates of neonatal failed intubation, oesophageal intubation, accidental extubation and reports of associated patient harm all suggest the value of a reliable airway monitor in NICU. Waveform capnography rapidly detects correct intubation with few false positives and immediately detects displacement or disconnection, the evidence for which we have previously set out [4-6].
Some neonatologists argue that continuous waveform capnography cannot be used in neonates. It is used routinely in neonatal anaesthesia. Others use it routinely during transfer of small neonates (eg 400g) (personal communication Dr James Tooley, Consultant, Bristol) sometimes only for it...
Dear authors,
Show MoreI read with great interest your article on multiple café-au-lait macules and movement disorder (1). I want to point out that probably an error happened during formatting of table 1. The term RASopathies is used to refer to a group of diseases caused by a mutation in a gene coding for a key component of the RAS-pathway and resulting in hyperactivation of the pathway. This group commonly includes Noonan syndrome, Neurofibromatosis type 1, Legius syndrome, LEOPARD syndrome (now referred to as Noonan syndrome with multiple lentigines), Costello syndrome, CFC syndrome, hereditary gingival fibromatosis, capillary malformation-arteriovenous malformation and Loh syndrome (2). It is confusing to find RASopathies next to Noonan, Legius and LEOPARD syndrome in the same column of table 1. In the same column Legius syndrome is listed as well as NF-like syndrome. Legius syndrome is listed followed by (PTPN11) and NF-like syndrome is followed by the gene (SPRED1). PTPN11 should be listed after Noonan syndrome because it is the most frequent cause of Noonan syndrome and it is not related to Legius syndrome. Legius syndrome is the same as NF1-like syndrome and only one of the two should be listed followed by (SPRED1). In our first publication (3) we named the condition neurofibromatosis 1-like syndrome but later is was renamed Legius syndrome (4).
Congenital mismatch repair deficiency (CMMRD) is another autosomal recessive condition with café-au-lait macules and...
I was interested to read the Archimedes article reviewing the structured question ‘in neonates who require ventilation, does waveform capnography give an accurate approximation of PaCO2?’ The findings such as the accuracy of ETCO2 decreases with the severity of lung disease (Grade B) adds to similar knowledge about waveform capnography when it was introduced in adults.
Whenever capnography is discussed however it should always be remembered that the primary reason for its introduction into clinical practice was to reliably ensure patients oxygenation and reduce the incidence of hypoxic brain damage, which it did so dramatically. The presence of a capnography waveform is the gold standard to demonstrate the integrity and correct position of an airway and establish that the patient is being ventilated with the intended oxygen. This eureka moment discovering that waveform capnography is more about oxygenation than accuracy of PaCO2 estimation is crucial for patient safety. The exact value of PaCO2 is secondary.
Unfortunately for over 20 years adult intensive care missed this eureka moment and consequently never started to use waveform capnography in adult ITUs when it was being universally introduced into operating theatres in the late 1980s [1].
Despite waveform capnography continuing to save many patients lives in operating theatres the argument that the accuracy of ETCO2 decreased with the severity of lung disease predominated in intensive care and w...
Show MoreWe welcome the comments made by Professor Andrew Williams, who has been a great supporter of our UK-wide study of children with progressive intellectual and neurological deterioration (PIND). The PIND Study uses the mechanism provided by the British Paediatric Surveillance Unit (BPSU), which is based in the Royal College of Paediatrics and Child Health. Since 1986 the BPSU has provided paediatricians in the United Kingdom with the means of investigating rare disorders of childhood. As Professor Williams points out there is a need to make research central to good paediatric practice and the BPSU continues to facilitate that.
Show MoreThe PIND Study is funded by the National Institute for Health Research (NIHR) Policy Research Programme to look for cases of variant Creutzfeldt-Jakob disease (vCJD) among the many neurodegenerative diseases of childhood. Since the PIND Study started in 1997 we have identified children with more than 190 of these rare disorders - that number constantly increases as new diseases and new genetic variants of known diseases are discovered. Thus our study not only provides the sole means of systematically searching for vCJD in children but also gives a unique oversight of the changing pattern of childhood neurodegenerative disease in the UK. We work closely with the National Creutzfeldt-Jakob Disease Research and Surveillance Unit which carries out surveillance for vCJD in adults.
Professor Williams highlights the fact that our work could not be...
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