Early Human Development 90 (2014) 941–946
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Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Best practice guidelines
Congenital diaphragmatic hernia Merrill McHoney ⁎ Royal Hospital for Sick Children Edinburgh, Sciennes Road, Edinburgh, EH1 1LF, UK
a r t i c l e
i n f o
a b s t r a c t There is a paucity of level 1 and level 2 evidence for best practice in surgical management of CDH. Antenatal imaging and prognostication is developing. Observed to expected lung-to-head ratio on ultrasound allows better predictive value over simple lung-to-head ratio. Based on 2 randomised studies, the verdict is still out in terms the best group and indication for antenatal intervention and their outcome. Tracheal occlusion is best suited for prospective randomised studies of benefit and outcome. Only one pilot randomised controlled study of thoracoscopic repair exists, suggesting increased acidosis; blood gases and CO2 levels should be closely monitored. Only poorly controlled retrospective studies suggest higher recurrence rates. Randomised studies on the outcome of thoracoscopic repair are needed. Careful selection, anaesthetic vigilance, monitoring and follow-up of these cases are required. There is no evidence to suggest the best patch material to decrease recurrences. Evidence suggests no benefit from routine fundoplication based on the one randomised study. Multi-disciplinary follow-up is required. This can be visits to different specialities, but may be best served by a multi-disciplinary one-stop clinic. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Congenital diaphragmatic hernia Antenatal management Tracheal occlusion Surgery Thoracoscopy Carbon dioxide Oxygenation Fundoplication Patch repair
Contents 1. 2.
Introduction . . . . . . . . . . . . Antenatal imaging and prognostication 2.1. MRI . . . . . . . . . . . . 3. Antenatal intervention . . . . . . . . 4. Thoracoscopic vs. open surgery . . . . 4.1. Best practice . . . . . . . . 5. Type of patch repair . . . . . . . . . 5.1. Best practice . . . . . . . . 6. Gastro-oesophageal disease . . . . . 6.1. Best practice . . . . . . . . 7. Long-term follow-up . . . . . . . . Conflict of interest statement . . . . . . . References . . . . . . . . . . . . . . .
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1. Introduction Congenital diaphragmatic hernia (CDH) is characterised by a spectrum developmental defects in the diaphragm caused by disordered embryogenesis, resulting in incomplete fusion of elements giving rise to the diaphragm. Ninety percent of CDH cases are found in a posterolateral defect (Bochdaleck hernia), and 9% are found in an anteriomedial defect (Morgagni hernia). The remainder of cases comprise the ⁎ Tel.: +44 131 536 0661/0768; fax: +44 131536 0665. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.earlhumdev.2014.09.013 0378-3782/© 2014 Elsevier Ireland Ltd. All rights reserved.
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relatively rarer forms of total absence of the diaphragm, absence of the central portion of the diaphragm, and oesophageal hiatal hernia. Most of classic CDH diagnosed at birth comprise the Bochdaleck type with a varying degree of the size of the defect. The incidence of CDH is 1 in 2,500 to 1 in 3,500 live births. Left-sided CDH is more common than right-sided, with a ratio of 6:1. Bilateral lesions are reported, but they are invariably fatal. Antenatal diagnosis and prognostication is increasing with sophisticated imaging techniques. Non-antenatally diagnosed cases can present in the early postnatal period with respiratory distress. Associated chromosomal abnormalities, lung hypoplasia, pulmonary vascular abnormality
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and cardiac abnormalities lead to a high mortality. Prompt neonatal management is the most important influence on outcome. Surgical correction has become a non-emergent secondary intervention. Lung hypoplasia plays a significant role in determining clinical course and outcome. The development of type II alveolar cells that produce surfactant is also inhibited, resulting in relative surfactant deficiency. Antenatal prediction of outcome in isolated CDH is based on this associated lung hypoplasia. The abnormal development of the pulmonary vasculature leads to pulmonary hypertension and increased pulmonary vasculature reactivity. The neonate is prone to episodes of hypoxia and hypercapnia, which in turn further increase the pulmonary hypertension and cause persistent foetal circulation. Persistent foetal circulation further worsens the hypercapnia and hypoxia. This viscous positive cycle can lead to severe physiological consequences in those most affected. The lung hypoplasia along with pulmonary hypertension is a detrimental patho-physiological process that affects outcome. Surgical management has changed. Antenatal assessment and intervention has been used to surgically treat patients with predicted poor outcome. Surgical morbidity is associated with the size of the defect and the need for patch repair. The advent of minimally invasive approach to surgical repair has developed but requires expert management of acidosis and oxygenation. Long-term morbidity (affecting multiple systems) is also high and can be related to both the underlying diagnosis as well as treatment. Feeding difficulties is common and gastro-oesophageal reflux can need surgical management. This review will summarize the available evidence for best practice in surgical management of CDH; antenatal imaging and intervention, operative approach, type of patch repair, surgical management of reflux and address long-term follow-up.
2. Antenatal imaging and prognostication Routine antenatal ultrasound scanning detects approximately 50–85% cases of CDH. Lung-to-head ratio (LHR: contralateral lung area to head circumference) measured by antenatal ultrasound is used to predict the severity and outcome in CDH and to predict patients with poor outcome for antenatal intervention. There are reports suggesting a good correlation, although some reports highlighted inconsistency in the predictive value of measured LHR [1]. This may be due to the ‘learning curve’ associated with the fast developing area of antenatal imaging, interpretation and prognostication. Part of the discrepancy may be due to different means and timing of estimating LHR. A uniform technique to avoid inter-operator variation and to unify data has been suggested by Jani et al. [2]. By standardising the methods of measurement using the longest diameter, the anteroposterior diameter at mid clavicle or a tracing method (preferably the latter as it seems to be most reproducible), errors in measurements can be avoided and unification of technique should allow better correlation. There are also problems inherent on using isolated LHR, as LHR changes with gestational age [2] and tends to underestimate the severity of the defect [3]. Greater consistency and accuracy in predictive value is obtained by using the observed to expected LHR (O/E LHR), and magnetic resonance imaging (MRI) total lung volume (TLV). The O/E LHR was developed in response to the observation that lung growth is 4 times that of head growth in the 3rd trimester [3]. The Antenatal-CDH-Registry Group [4] demonstrated that the O/E LHR (by taking a transverse section of the foetal chest demonstrating the four-chamber view of the heart and multiplying the contralateral lung area's longest diameter by the longest perpendicular to it) eliminates the effect of gestational age. In foetuses with both leftand right-sided CDH, the measurement of the O/E LHR provides a useful prediction of subsequent survival. The O/E LHR is lower in foetuses with CDH compared to normal foetuses, and lower still in babies who die with CDH than those who survive [2]. There was however some overlap in values between survivors and non-survivors. The survival for left sided lesion related to O/E LHR with liver down was as follows:
≤25%:30% survival; 26–35%:62% survival; 36–45%:75% survival; 46– 55%: 90% survival; and N55%: 85% survival [4]. Although LHR is predictive of mortality in CDH, it is not strongly correlated with morbidity. 2.1. MRI Foetal MRI may have a role in providing more specific information to aid prognostic decision, and can be offered at 24 and 34 weeks gestation. Contralateral lung volume/TLV on MRI strongly correlates with lung area measured on US. There is currently no evidence that foetal MRI is superior to ultrasound at predicting outcome. In one study, foetal MRI TLV permitted calculation of lung volumes, but these volumes were not predictive of outcome [5]. This may depend on the precise method used. Alternatively, foetal MRI for lung volume may yield additional useful information (e.g. % of liver herniation) and give better receiver operator curves for prediction [6]. O/E TLV obtained by MRI scan correlates with US derived LHR but without the operator dependant nature of measurements and maternal and foetal motion artefacts [6]. Best practice: Use of O/E LHR on ultrasound allows better predictive value over LHR alone. Standardisation of the method of measurement should allow better reproducibility. 3. Antenatal intervention Although antenatal trachea occlusion (TO) was suggested as a potential inducer of increased foetal lung growth in animal models, clinical benefits are not always clear from the research done to date. Initial investigation showed mixed results in terms of both lung growth and survival in cohort studies. Further advance on the technique and management has allowed units to offer antenatal foetal endoscopic tracheal occlusion (FETO) by endoscopic plugging in management of severe cases of CDH. There have been a few randomized trials reporting outcome of TO. Harrision et al. [1] randomized 24 patients with left CDH, liver up and LHR b 1.4 and assessed the survival effect of TO performed via maternal laparotomy. Early termination of trial enrolment was needed because survival in the control group was better than anticipated and benefit was not evident from the plugging. There may have been some modest improvements in lung function but no discernible clinical benefit and no differences in neurodevelopmental, respiratory, surgical, growth and nutritional outcomes at 1 and 2 years of age. By contrast, Ruano et al. [7] randomised 41 foetuses (any side; LHR b 1.0, liver herniation and no other detectable anomalies; 38/41 received allocated treatment) and found a significant 6-month survival advantage associated with antenatal plugging (received treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived; relative risk 10.0; 95% CI, 1.4–70.6). There are differences in both studies which may account for the difference in outcome between them. There were differences in the LHR which allowed inclusion into both studies. The more severely affected foetuses in the latter study may have therefore benefited from TO, whereas the effect on less severely affected foetuses was not marked. There were differences in technique (maternal laparotomy versus fetal endoscopic approach), which may have influenced incidence of preterm labour, resulting in a 5-week difference in the gestational age at delivery between both studies, with obvious confounding effects. Further studies are needed to clarify the patient groups that may benefit from this intervention. Cohort studies demonstrate that there is an antenatal response (preand post-FETO O/E LHR or TFLV) to plugging in foetuses with CDH which may provide independent prediction of postnatal survival. Jani et al. [8] reported on multicentre study of 210 FETO cases. They found a survival advantage when compared with expected survival as predicted by O/E LHR. In addition to the obstetric complications of FETO, the complication to the foetus includes tracheal changes (dilation and
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tracheomalacia) secondary to pressure from the balloon. FETO has a significant impact on tracheal size of infants with CDH (Fig. 1), but tracheal size does not seem to affect survival or the requirement for early respiratory support. Best practice: It would seem from the results above that the verdict is still out in terms the best group and indication for antenatal intervention and outcome. Ongoing enrolment into FETO would be best suited for prospective randomised studies to report on benefit and outcome. One going trial in Europe aims to enrol patients in with severe hypoplasia (O/E LHR b25%) and randomized to FETO. The acronym for the trial is TOTAL (Tracheal Occlusion to Accelerate Lung Growth, www.totaltrial.eu). 4. Thoracoscopic vs. open surgery Surgical management of CDH can be via a conventional open abdominal approach or a minimally invasive surgery (MIS) approach via laparoscopy or thoracoscopy. In recent years, there has been increasing use of MIS in paediatric and neonatal surgery, including the management of CDH. There are theoretical advantages of less tissue trauma, less pain, and less cosmetic deformity. There may be disadvantages though. CO2 is absorbed during insufflation into the chest and creation of a capnothorax [9,10], which can lead to significant metabolic and physiological changes. The impaired respiratory capacity imposed by lung collapse has significant implications for oxygenation and CO2 excretion and increase in arterial-alveolar CO2 gradient. Coupled with impaired ventilation, this can lead to a marked increase in end-tidal CO2 (EtCO2) in children undergoing thoracoscopy. The increase in CO2 is generally higher than that seen during laparoscopy, and higher in smaller children undergoing single lung ventilation. Intra-abdominal absorption of insufflated form the abdomen seems to peak around 30 min into surgery, with approximately 20% of CO2 expired derived from absorption, and decreases back to preoperative levels 30 min postoperatively [9]. Thoracic insufflation of CO2 may have a different absorption profile, as it seems not to reach steady state within 30 min [10], with a greater percentage (up to 30%) of exhaled CO2 derived from absorption during thoracoscopy than laparoscopy. The exact absorption
Fig. 1. Chest Xray of patient with right sided CDH who had undergone antenatal tracheal occlusion. Note the hugely distended trachea highlighted by the air lucency in the upper chest.
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and elimination profile may differ depending on CO2 pressures, metabolic changes and patient factors. However, generally there seems to be different profiles between abdominal and thoracic insufflation. In CDH, the persistent pulmonary hypertension, lung hypoplasia and pulmonary vasculature hyperactivity that accompany the disease are additional confounding factors in the management of the increased CO2 load. Any significant acidosis may increase shunting and worsen any pulmonary hypertension with deleterious effects on systemic perfusion pressures, ventilation and oxygenation. The pathophysiological effects of intraoperative capnothorax, hypercapnia, hypoxia are complex, with an increase in ETCO2 during thoracoscopy in children associated with decrease in systolic and diastolic blood pressure, but also a beneficial effect of hypercapnia by increasing cardiac output. Permissive hypercapnia is a mainstay of ventilatory management in the neonatal management of CDH and reduces morbidity. The limits of intraoperative ‘permissive hypercapnia’ in CDH have not been established. It is also not know if the handling of CO2 differs during laparoscopy compared to thoracoscopy in neonates with CDH, as both cavities are effectively a single unit in these patients. High-frequency ventilation has been suggested by some as one means of intraoperative management of thoracoscopy in the CDH patient, with a few studies reporting on adequate outcome [11]. Only few studies addressed intraoperative hypercapnia and oxygenation in detail. Szavay et al. [12] retrospectively found no difference in maximum CO2 levels between open and MIS approaches. Other studies demonstrated differences in pH, but with little physiological effect. Most studies have however confirmed a significant intraoperative increase in CO2 excretion [13] and/or acidosis during thoracoscopic CDH repair. One randomised controlled pilot study has been performed looking at the effect of thoracoscopy in 10 neonates randomised to open and thoracoscopic repair. There was a significant intraoperative hypercapnia and acidosis in the thoracoscopic patients [14]. There are also concerns about the systemic effect of hypercapnia and on cerebral perfusion. Although neonatal piglets demonstrate efficient pulmonary auto-regulation during one-lung ventilation, the effects on cerebral perfusion has not been fully investigated. COCO2 levels may alter both cerebral blood flow and metabolism. It is therefore worth considering the effects of CO2 on cerebral metabolism and oxygenation even though there have been no documented adverse effects of CO2 insufflation during thoracoscopy in CDH patients. Only one study has investigated cerebral perfusion during thoracoscopy in neonates and showed a significant decrease in cerebral oxygenation during (from 87% ± 4% at the start to 75% ± 5% at end of operation) and after thoracoscopic CDH and oesophageal atresia repair [10], although the clinical effects of this is not known. It is also not known if the effect is directly secondary to systemic CO2 levels. This needs further research. One other concern about the thoracoscopic repair of CDH is recurrence. Possible explanations for higher recurrences during thoracoscopic approach include the acquisition of the learning curve for the procedure, the use of patch repair during thoracoscopy and the technical difficulties in achieving a complete diaphragmatic closure in these neonates. Many papers have quoted a higher recurrence rate after thoracoscopic repair of CDH [13], and after laparoscopic repair of Morgagni hernia. Tsao et al (Congenital Diaphragmatic Hernia Study Group) [15] reported on 4,390 infants limited to short-term recurrence during initial hospitalization. Of 151 MIS repairs, 12 recurred (7.9%) compared to 114 for open (2.7%), with a significant increased odds for recurrence (OR 3.59, 95% CI: 1.92–6.71) after adjusting for confounding factors. Infants that required a patch repair had a significantly higher recurrence rate (3.8% primary vs. 2.0% patch, p b 0.05). MIS repairs that used a patch had the highest recurrence rate at 8.8%. However, there was a significant increased odds of survival for infants undergoing MIS repairs (OR 5.57; 95% CI: 1.34–23.14). One systemic review of 3 eligible published series concluded that there is a higher incidence of recurrence with MIS (OR 3.2) but a non-significant trend to lower incidence of death (OR 0.33) [16].
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Not all report a higher recurrence rate however. Fishman et al. [17] found no clear difference in recurrence rate between approaches. Recurrence rates comparable with open surgery (as low as 3.6%) are reported. Some suggest an extracorporeal corner stitch, liberal prosthetic patch use, lower insufflation pressures and two experienced surgeons as means to decrease recurrence rates after thoracoscopy. There are similar incidence of complications between laparoscopic and thoracoscopic approaches. There may be selection criteria, including anatomical (stomach in the abdomen) and physiological (minimal ventilator support; peak inspiratory pressures in the low 20s), which allow safe MIS approach in these children. Oxygenation index (N3.0) has been shown as the only selection criteria significantly predictive of postoperative complications for thoracoscopic approach [18]. However, no randomised or even prospective data exist. 4.1. Best practice Most papers are retrospective case or cohort studies, with only one randomise pilot study. During thoracoscopic repair of CDH, both blood gases and ETCO2 should be closely monitored and correlated in these patients, especially when significant changes in ETCO2 are noted. While further studies are awaited on which further guidelines can be developed, careful selection [18], anaesthetic vigilance, monitoring and surveillance [10,13] and follow-up of these cases are required. Prospective, controlled and randomised studies on the outcome of thoracoscopic repair are needed to inform further practice. 5. Type of patch repair Patch repair of CDH is associated with an almost universally higher rate of recurrence than with primary repair; although this is not reported by some. The cause for increased recurrence after a patch repair can be technical, or related to the patch material. Studies have tried to identify any factors associated with the patch material itself. In patients requiring a patch repair, the three most common patch materials used are as follows: Gortex® (synthetic nonabsorbable polytetrafluoroethylene; PTFE), Surgisis® (non-cross-linked porcine intestine) and Permacol® (cross-linked porcine dermis). Others include AlloDerm® (acellular human cadaveric dermis), PTFE and polypropylene (Marlex®) and foetal bovine dermal collagen (Surgimend®). Tissue engineering is a fast developing area and may provide cellular scaffolding techniques which may prove advantageous in the future. The use of human biological scaffolding (allografts) may increase significantly with those developments. For now we concentrate on the commonly available xenografts and synthetic materials. There are no randomised controlled trials on type of patch repair in CDH patients. Most reports addressing this issue are retrospective cohort studies. Although there are a couple of randomised studies in animals suggest biological patches are associated with better integration to the chest wall, more muscle growth within the newly formed diaphragmatic tissue, this has not been proved in clinical practice. Despite the vast range of patch materials to choose from and the potential pros and cons between them, there are no type 1 or 2 evidence for choosing between non-biological and biological; and even within different biological materials. Type 4 (retrospective) studies exist. Some very small reports suggest better outcome with Permacol compared to Gore-Tex. However, Laituri et al. [19] found the incidence of small bowel obstruction (SBO) in patients with a nonabsorbable mesh was 17% and was associated with a 50% recurrence rate and 67% re-recurrence rate. Whereas Surgisis was associated with 19% incidence of SBO, a recurrence rate of 22% and a 50% re-recurrence rate. However, Alloderm® had significantly higher complications than both. Contrary to the above studies, Jawaid et al. [20] used Gore-Tex® patches in 35 and Surgisis® patches in 2 patients; both of the latter suffered early recurrences and were re-done using Gore-Tex®. Romao et al.
[21] found no difference in recurrence rate, adhesional obstruction or mortality between Surgisis and nonabsorbable synthetic (PTFE) in their series of 22 patients. They performed a meta-analysis along with the 2 other published papers and failed to show any difference in recurrence and SBO rates between the 2 materials. 5.1. Best practice There is no firm evidence in the literature to base a decision on. There seems to be the need for prospective controlled study to identify the best patch material for repair when needed. 6. Gastro-oesophageal disease Gastro-oesophageal reflux is seen in 50–90% of patients and should be treated by merit. Overall, however, the requirement for fundoplication is higher in the CDH population than in normal children. There may be factors which increase the need for fundoplication in CDH. However, motility of the oesophagus and the lower oesophageal sphincter tone seems unimpaired in survivors. Patch repair, presence of liver in the chest and need for ECMO have traditionally been cited as increasing the likelihood of needing fundoplication. Verbelen et al. [22] recently found that along with presence of liver in the chest, having FETO increases the risk of needing fundoplication. The rate of recurrence post fundoplication seems higher in CDH patients compared to normal children. Some retrospective reports suggest that fundoplication at the time of CDH repair decreased the incidence of growth failure. Guner et al. [23] selected 13 patients with anatomical abnormalities that would predispose to reflux and performed anterior fundoplication successfully, with 2 patients needing conversion to 360° fundoplication later in life; none of the 19 patients in their ‘control’ group needed fundoplication. It is proposed that routine fundoplication was only helpful in a sub group (liver up and patch) with predictable severe reflux. Only one study aimed to determine the value of routine fundoplication in a randomized patient-blinded prospective study of all patients having open repair [24]. The benefit of routine antireflux surgery (anterior hemi-fundoplication) at the time of repair of CDH was evaluated in 79 patients. At 6 months of age, there were less symptoms in the fundoplication group, but no perceived benefit of fundoplication beyond that time. There was no difference in the growth curve of fundoplication patients compared to control at any time. This probably represents the natural history of reflux, even within CDH. Therefore, they concluded that preventive antireflux surgery cannot be recommended as a standard procedure. 6.1. Best practice There is no firm evidence to suggest benefit from routine fundoplication based on the one randomised study done. There may be different need for fundoplication in patients with high risk factors, but no prospectively controlled study exists exploring this. 7. Long-term follow-up There are many multi-system and multi-disciplinary issues in CDH patients in the long term. Chronic lung disease is a common sequel in severely affected patients. Alveolar growth continues up to 8 years of age, and children can outgrow any mild restrictions to exercise tolerance and susceptibility to chest infections. An increased incidence of asthma is seen. Continued pulmonary hypertension into infancy and childhood are associated with poor outcome. There is a late mortality due to chronic lung disease and associated or secondary cardiac dysfunction, which can be as late as 4 years of age. Gastro-oesophageal reflux, feeding issues and poor growth are gastrointestinal/nutritional issues. Occasionally, these feeding issues
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need medical and/or surgical (feeding tubes/gastrostomies, fundoplication, etc.) management to improve outcome or quality of life. Surgical complications of intestinal adhesions and recurrent herniation can occur. Skeletal deformity secondary to chest wall deformity may need surgical correction later in life. Neurodevelopmental delay and hearing loss are nonsurgical complications, which are consequences of poor oxygenation, and are twice as common in children who receive ECMO support. The existence of intracerebral injuries and the classification of its severity are the major predictors of neurodevelopmental outcome. Other predictors of poor neurodevelopmental outcome are right sided CDH, liver up, need for patch and chronic lung disease. These neurodevelopmental and neurofunctional outcomes in children with congenital diaphragmatic hernia have encouraged the need for multi-disciplinary follow-up to both identify and manage these. Although there are no randomised studies to prove the clinical usefulness of multi-disciplinary follow-up, the impact of these have been established by good prospective studies of outcomes in this setting suggesting identification and management can aid at least some improvement [25]. These wide-ranging systemic morbidities, which can affect the CDH patient in the long term, need a variety of medical specialities involvement in their specific field, but with inter-specialty correlation in the overall care. Multi-disciplinary follow-up is required. This can take the form of visits to the different specialities involved in an individualised manner. But those requirements may also be best served by a multidisciplinary one-stop clinic. The Scottish Diaphragmatic Hernia Clinical Network (http://www. sdhcn.scot.nhs.uk/) and the Canadian Pediatric Surgery Network (http://www.capsnetwork.org/) are examples of networks working with the aims of producing multi-disciplinary guidelines for counselling, research, development and follow-up in patients with CDH. Key guidelines: • Antenatal US can be used to help prognosticate postoperative outcome if uniformity in measuring and reporting are used. • The use of observed to expected antenatal measurements is preferred as they give more specific and accurate information • Antenatal intervention in the group of patients with worst outcome should be part of ongoing clinical trials with good follow-up and reporting of outcome. • Thoracoscopic approach to CDH should be done by those with sufficient MIS experience, with close liaison with anaesthetic colleagues for patient selection, anaesthetic vigilance, monitoring and surveillance and follow-up. • Regular monitoring of intraoperative blood gases and ETCO2 is necessary (1 randomised controlled pilot study demonstration decreased pH and herpercapnia). Use of routine regional oxygenation (especially cerebral) should be considered, both for clinical correlation and outcome and for research. • There is no clear evidence with regard to the best results in those requiring a patch. • Routine fundoplication at the time of CDH repair is not supported by the evidence of 1 randomised controlled study. • Multi-disciplinary follow-up is required, and may be suited for a multi-disciplinary one-stop clinic. Research directions: • Antenatal classification of disease severity needs research into the standardisation of methodology to predict outcome and guide intervention. Intervention should probably continue as part of a randomised trials for research and development. • The safety, intraoperative management and outcome from thoracoscopic surgery need both laboratory and clinical based research to clarify the issues around acidosis and oxygenation. Randomised trials are needed to help with the best approach for surgical management. • Biological advances and tissue engineering focusing on the
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development of biological diaphragmatic tissue replacement in those needing patching, to minimise recurrence and complications. Conflict of interest statement There are no financial and personal relationships with other people or organizations that could inappropriately influence this work to disclose. References [1] Harrison MR, Keller RL, Hawgood SB, Kitterman JA, Sandberg PL, Farmer DL, et al. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med November 13 2003;349(20):1916–24. [2] Jani JC, Peralta CF, Nicolaides KH. Lung-to-head ratio: a need to unify the technique. Ultrasound Obstet Gynecol January 2012;39(1):2–6. [3] Peralta CF, Cavoretto P, Csapo B, Vandecruys H, Nicolaides KH. Assessment of lung area in normal fetuses at 12-32 weeks. Ultrasound Obstet Gynecol December 2005;26(7):718–24. [4] Jani J, Nicolaides KH, Keller RL, Benachi A, Peralta CF, Favre R, et al. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol July 2007;30(1): 67–71. [5] Walsh DS, Hubbard AM, Olutoye OO, Howell LJ, Crombleholme TM, Flake AW, et al. Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia. Am J Obstet Gynecol November 2000; 183(5):1067–9. [6] Bebbington M, Victoria T, Danzer E, Moldenhauer J, Khalek N, Johnson M, et al. Comparison of ultrasound and magnetic resonance imaging parameters in predicting survival in isolated left-sided congenital diaphragmatic hernia. Ultrasound Obstet Gynecol December 4 2013;43(6):670–4. [7] Ruano R, Yoshisaki CT, da Silva MM, Ceccon ME, Grasi MS, Tannuri U, et al. A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia. Ultrasound Obstet Gynecol January 2012;39(1):20–7. [8] Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol September 2009;34(3):304–10. [9] Pacilli M, Pierro A, Kingsley C, Curry JI, Herod J, Eaton S. Absorption of carbon dioxide during laparoscopy in children measured using a novel mass spectrometric technique. Br J Anaesth August 2006;97(2):215–9. [10] Bishay M, Giacomello L, Retrosi G, Thyoka M, Nah SA, McHoney M, et al. Decreased cerebral oxygen saturation during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia in infants. J Pediatr Surg January 2011;46(1):47–51. [11] Mortellaro VE, Fike FB, Adibe OO, Juang D, Aguayo P, Ostlie DJ, et al. The use of highfrequency oscillating ventilation to facilitate stability during neonatal thoracoscopic operations. J Laparoendosc Adv Surg Tech A November 2011;21(9):877–9. [12] Szavay PO, Obermayr F, Maas C, Luenig H, Blumenstock G, Fuchs J. Perioperative outcome of patients with congenital diaphragmatic hernia undergoing open versus minimally invasive surgery. J Laparoendosc Adv Surg Tech A April 2012;22(3): 285–9. [13] McHoney M, Giacomello L, Nah SA, De CP, Kiely EM, Curry JI, et al. Thoracoscopic repair of congenital diaphragmatic hernia: intraoperative ventilation and recurrence. J Pediatr Surg February 2010;45(2):355–9. [14] Bishay M, Giacomello L, Retrosi G, Thyoka M, Garriboli M, Brierley J, et al. Hypercapnia and acidosis during open and thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia: results of a pilot randomized controlled trial. Ann Surg December 2013;258(6):895–900. [15] Tsao K, Lally PA, Lally KP. Minimally invasive repair of congenital diaphragmatic hernia. J Pediatr Surg June 2011;46(6):1158–64. [16] Lansdale N, Alam S, Losty PD, Jesudason EC. Neonatal endosurgical congenital diaphragmatic hernia repair: a systematic review and meta-analysis. Ann Surg July 2010;252(1):20–6. [17] Fishman JR, Blackburn SC, Jones NJ, Madden N, De CD, Haddad MJ, et al. Does thoracoscopic congenital diaphragmatic hernia repair cause a significant intraoperative acidosis when compared to an open abdominal approach? J Pediatr Surg March 2011;46(3):458–61. [18] Gomes FC, Kuhn P, Lacreuse I, Kasleas C, Philippe P, Podevin G, et al. Congenital diaphragmatic hernia: an evaluation of risk factors for failure of thoracoscopic primary repair in neonates. J Pediatr Surg March 2013;48(3):488–95. [19] Laituri CA, Garey CL, Valusek PA, Fike FB, Kaye AJ, Ostlie DJ, et al. Outcome of congenital diaphragmatic hernia repair depending on patch type. Eur J Pediatr Surg November 2010;20(6):363–5. [20] Jawaid WB, Qasem E, Jones MO, Shaw NJ, Losty PD. Outcomes following prosthetic patch repair in newborns with congenital diaphragmatic hernia. Br J Surg December 2013;100(13):1833–7. [21] Romao RL, Nasr A, Chiu PP, Langer JC. What is the best prosthetic material for patch repair of congenital diaphragmatic hernia? Comparison and meta-analysis of porcine small intestinal submucosa and polytetrafluoroethylene. J Pediatr Surg August 2012;47(8):1496–500. [22] Verbelen T, Lerut T, Coosemans W, De LP, Nafteux P, Van RD, et al. Antireflux surgery after congenital diaphragmatic hernia repair: a plea for a tailored approach. Eur J Cardiothorac Surg August 2013;44(2):263–7.
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[23] Guner YS, Elliott S, Marr CC, Greenholz SK. Anterior fundoplication at the time of congenital diaphragmatic hernia repair. Pediatr Surg Int August 2009; 25(8):715–8. [24] Maier S, Zahn K, Wessel LM, Schaible T, Brade J, Reinshagen K. Preventive antireflux surgery in neonates with congenital diaphragmatic hernia: a single-blinded prospective study. J Pediatr Surg August 2011;46(8):1510–5.
[25] Danzer E, Gerdes M, D'Agostino JA, Hoffman C, Bernbaum J, Bebbington MW, et al. Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life. J Perinatol November 2013;33(11): 893–8.
Contents lists available at ScienceDirect
Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev
Best practice guidelines
Congenital diaphragmatic hernia Merrill McHoney ⁎ Royal Hospital for Sick Children Edinburgh, Sciennes Road, Edinburgh, EH1 1LF, UK
a r t i c l e
i n f o
a b s t r a c t There is a paucity of level 1 and level 2 evidence for best practice in surgical management of CDH. Antenatal imaging and prognostication is developing. Observed to expected lung-to-head ratio on ultrasound allows better predictive value over simple lung-to-head ratio. Based on 2 randomised studies, the verdict is still out in terms the best group and indication for antenatal intervention and their outcome. Tracheal occlusion is best suited for prospective randomised studies of benefit and outcome. Only one pilot randomised controlled study of thoracoscopic repair exists, suggesting increased acidosis; blood gases and CO2 levels should be closely monitored. Only poorly controlled retrospective studies suggest higher recurrence rates. Randomised studies on the outcome of thoracoscopic repair are needed. Careful selection, anaesthetic vigilance, monitoring and follow-up of these cases are required. There is no evidence to suggest the best patch material to decrease recurrences. Evidence suggests no benefit from routine fundoplication based on the one randomised study. Multi-disciplinary follow-up is required. This can be visits to different specialities, but may be best served by a multi-disciplinary one-stop clinic. © 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Congenital diaphragmatic hernia Antenatal management Tracheal occlusion Surgery Thoracoscopy Carbon dioxide Oxygenation Fundoplication Patch repair
Contents 1. 2.
Introduction . . . . . . . . . . . . Antenatal imaging and prognostication 2.1. MRI . . . . . . . . . . . . 3. Antenatal intervention . . . . . . . . 4. Thoracoscopic vs. open surgery . . . . 4.1. Best practice . . . . . . . . 5. Type of patch repair . . . . . . . . . 5.1. Best practice . . . . . . . . 6. Gastro-oesophageal disease . . . . . 6.1. Best practice . . . . . . . . 7. Long-term follow-up . . . . . . . . Conflict of interest statement . . . . . . . References . . . . . . . . . . . . . . .
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1. Introduction Congenital diaphragmatic hernia (CDH) is characterised by a spectrum developmental defects in the diaphragm caused by disordered embryogenesis, resulting in incomplete fusion of elements giving rise to the diaphragm. Ninety percent of CDH cases are found in a posterolateral defect (Bochdaleck hernia), and 9% are found in an anteriomedial defect (Morgagni hernia). The remainder of cases comprise the ⁎ Tel.: +44 131 536 0661/0768; fax: +44 131536 0665. E-mail address: [email protected].
http://dx.doi.org/10.1016/j.earlhumdev.2014.09.013 0378-3782/© 2014 Elsevier Ireland Ltd. All rights reserved.
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relatively rarer forms of total absence of the diaphragm, absence of the central portion of the diaphragm, and oesophageal hiatal hernia. Most of classic CDH diagnosed at birth comprise the Bochdaleck type with a varying degree of the size of the defect. The incidence of CDH is 1 in 2,500 to 1 in 3,500 live births. Left-sided CDH is more common than right-sided, with a ratio of 6:1. Bilateral lesions are reported, but they are invariably fatal. Antenatal diagnosis and prognostication is increasing with sophisticated imaging techniques. Non-antenatally diagnosed cases can present in the early postnatal period with respiratory distress. Associated chromosomal abnormalities, lung hypoplasia, pulmonary vascular abnormality
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and cardiac abnormalities lead to a high mortality. Prompt neonatal management is the most important influence on outcome. Surgical correction has become a non-emergent secondary intervention. Lung hypoplasia plays a significant role in determining clinical course and outcome. The development of type II alveolar cells that produce surfactant is also inhibited, resulting in relative surfactant deficiency. Antenatal prediction of outcome in isolated CDH is based on this associated lung hypoplasia. The abnormal development of the pulmonary vasculature leads to pulmonary hypertension and increased pulmonary vasculature reactivity. The neonate is prone to episodes of hypoxia and hypercapnia, which in turn further increase the pulmonary hypertension and cause persistent foetal circulation. Persistent foetal circulation further worsens the hypercapnia and hypoxia. This viscous positive cycle can lead to severe physiological consequences in those most affected. The lung hypoplasia along with pulmonary hypertension is a detrimental patho-physiological process that affects outcome. Surgical management has changed. Antenatal assessment and intervention has been used to surgically treat patients with predicted poor outcome. Surgical morbidity is associated with the size of the defect and the need for patch repair. The advent of minimally invasive approach to surgical repair has developed but requires expert management of acidosis and oxygenation. Long-term morbidity (affecting multiple systems) is also high and can be related to both the underlying diagnosis as well as treatment. Feeding difficulties is common and gastro-oesophageal reflux can need surgical management. This review will summarize the available evidence for best practice in surgical management of CDH; antenatal imaging and intervention, operative approach, type of patch repair, surgical management of reflux and address long-term follow-up.
2. Antenatal imaging and prognostication Routine antenatal ultrasound scanning detects approximately 50–85% cases of CDH. Lung-to-head ratio (LHR: contralateral lung area to head circumference) measured by antenatal ultrasound is used to predict the severity and outcome in CDH and to predict patients with poor outcome for antenatal intervention. There are reports suggesting a good correlation, although some reports highlighted inconsistency in the predictive value of measured LHR [1]. This may be due to the ‘learning curve’ associated with the fast developing area of antenatal imaging, interpretation and prognostication. Part of the discrepancy may be due to different means and timing of estimating LHR. A uniform technique to avoid inter-operator variation and to unify data has been suggested by Jani et al. [2]. By standardising the methods of measurement using the longest diameter, the anteroposterior diameter at mid clavicle or a tracing method (preferably the latter as it seems to be most reproducible), errors in measurements can be avoided and unification of technique should allow better correlation. There are also problems inherent on using isolated LHR, as LHR changes with gestational age [2] and tends to underestimate the severity of the defect [3]. Greater consistency and accuracy in predictive value is obtained by using the observed to expected LHR (O/E LHR), and magnetic resonance imaging (MRI) total lung volume (TLV). The O/E LHR was developed in response to the observation that lung growth is 4 times that of head growth in the 3rd trimester [3]. The Antenatal-CDH-Registry Group [4] demonstrated that the O/E LHR (by taking a transverse section of the foetal chest demonstrating the four-chamber view of the heart and multiplying the contralateral lung area's longest diameter by the longest perpendicular to it) eliminates the effect of gestational age. In foetuses with both leftand right-sided CDH, the measurement of the O/E LHR provides a useful prediction of subsequent survival. The O/E LHR is lower in foetuses with CDH compared to normal foetuses, and lower still in babies who die with CDH than those who survive [2]. There was however some overlap in values between survivors and non-survivors. The survival for left sided lesion related to O/E LHR with liver down was as follows:
≤25%:30% survival; 26–35%:62% survival; 36–45%:75% survival; 46– 55%: 90% survival; and N55%: 85% survival [4]. Although LHR is predictive of mortality in CDH, it is not strongly correlated with morbidity. 2.1. MRI Foetal MRI may have a role in providing more specific information to aid prognostic decision, and can be offered at 24 and 34 weeks gestation. Contralateral lung volume/TLV on MRI strongly correlates with lung area measured on US. There is currently no evidence that foetal MRI is superior to ultrasound at predicting outcome. In one study, foetal MRI TLV permitted calculation of lung volumes, but these volumes were not predictive of outcome [5]. This may depend on the precise method used. Alternatively, foetal MRI for lung volume may yield additional useful information (e.g. % of liver herniation) and give better receiver operator curves for prediction [6]. O/E TLV obtained by MRI scan correlates with US derived LHR but without the operator dependant nature of measurements and maternal and foetal motion artefacts [6]. Best practice: Use of O/E LHR on ultrasound allows better predictive value over LHR alone. Standardisation of the method of measurement should allow better reproducibility. 3. Antenatal intervention Although antenatal trachea occlusion (TO) was suggested as a potential inducer of increased foetal lung growth in animal models, clinical benefits are not always clear from the research done to date. Initial investigation showed mixed results in terms of both lung growth and survival in cohort studies. Further advance on the technique and management has allowed units to offer antenatal foetal endoscopic tracheal occlusion (FETO) by endoscopic plugging in management of severe cases of CDH. There have been a few randomized trials reporting outcome of TO. Harrision et al. [1] randomized 24 patients with left CDH, liver up and LHR b 1.4 and assessed the survival effect of TO performed via maternal laparotomy. Early termination of trial enrolment was needed because survival in the control group was better than anticipated and benefit was not evident from the plugging. There may have been some modest improvements in lung function but no discernible clinical benefit and no differences in neurodevelopmental, respiratory, surgical, growth and nutritional outcomes at 1 and 2 years of age. By contrast, Ruano et al. [7] randomised 41 foetuses (any side; LHR b 1.0, liver herniation and no other detectable anomalies; 38/41 received allocated treatment) and found a significant 6-month survival advantage associated with antenatal plugging (received treatment analysis, 10/19 (52.6%) infants in the FETO group and 1/19 (5.3%) controls survived; relative risk 10.0; 95% CI, 1.4–70.6). There are differences in both studies which may account for the difference in outcome between them. There were differences in the LHR which allowed inclusion into both studies. The more severely affected foetuses in the latter study may have therefore benefited from TO, whereas the effect on less severely affected foetuses was not marked. There were differences in technique (maternal laparotomy versus fetal endoscopic approach), which may have influenced incidence of preterm labour, resulting in a 5-week difference in the gestational age at delivery between both studies, with obvious confounding effects. Further studies are needed to clarify the patient groups that may benefit from this intervention. Cohort studies demonstrate that there is an antenatal response (preand post-FETO O/E LHR or TFLV) to plugging in foetuses with CDH which may provide independent prediction of postnatal survival. Jani et al. [8] reported on multicentre study of 210 FETO cases. They found a survival advantage when compared with expected survival as predicted by O/E LHR. In addition to the obstetric complications of FETO, the complication to the foetus includes tracheal changes (dilation and
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tracheomalacia) secondary to pressure from the balloon. FETO has a significant impact on tracheal size of infants with CDH (Fig. 1), but tracheal size does not seem to affect survival or the requirement for early respiratory support. Best practice: It would seem from the results above that the verdict is still out in terms the best group and indication for antenatal intervention and outcome. Ongoing enrolment into FETO would be best suited for prospective randomised studies to report on benefit and outcome. One going trial in Europe aims to enrol patients in with severe hypoplasia (O/E LHR b25%) and randomized to FETO. The acronym for the trial is TOTAL (Tracheal Occlusion to Accelerate Lung Growth, www.totaltrial.eu). 4. Thoracoscopic vs. open surgery Surgical management of CDH can be via a conventional open abdominal approach or a minimally invasive surgery (MIS) approach via laparoscopy or thoracoscopy. In recent years, there has been increasing use of MIS in paediatric and neonatal surgery, including the management of CDH. There are theoretical advantages of less tissue trauma, less pain, and less cosmetic deformity. There may be disadvantages though. CO2 is absorbed during insufflation into the chest and creation of a capnothorax [9,10], which can lead to significant metabolic and physiological changes. The impaired respiratory capacity imposed by lung collapse has significant implications for oxygenation and CO2 excretion and increase in arterial-alveolar CO2 gradient. Coupled with impaired ventilation, this can lead to a marked increase in end-tidal CO2 (EtCO2) in children undergoing thoracoscopy. The increase in CO2 is generally higher than that seen during laparoscopy, and higher in smaller children undergoing single lung ventilation. Intra-abdominal absorption of insufflated form the abdomen seems to peak around 30 min into surgery, with approximately 20% of CO2 expired derived from absorption, and decreases back to preoperative levels 30 min postoperatively [9]. Thoracic insufflation of CO2 may have a different absorption profile, as it seems not to reach steady state within 30 min [10], with a greater percentage (up to 30%) of exhaled CO2 derived from absorption during thoracoscopy than laparoscopy. The exact absorption
Fig. 1. Chest Xray of patient with right sided CDH who had undergone antenatal tracheal occlusion. Note the hugely distended trachea highlighted by the air lucency in the upper chest.
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and elimination profile may differ depending on CO2 pressures, metabolic changes and patient factors. However, generally there seems to be different profiles between abdominal and thoracic insufflation. In CDH, the persistent pulmonary hypertension, lung hypoplasia and pulmonary vasculature hyperactivity that accompany the disease are additional confounding factors in the management of the increased CO2 load. Any significant acidosis may increase shunting and worsen any pulmonary hypertension with deleterious effects on systemic perfusion pressures, ventilation and oxygenation. The pathophysiological effects of intraoperative capnothorax, hypercapnia, hypoxia are complex, with an increase in ETCO2 during thoracoscopy in children associated with decrease in systolic and diastolic blood pressure, but also a beneficial effect of hypercapnia by increasing cardiac output. Permissive hypercapnia is a mainstay of ventilatory management in the neonatal management of CDH and reduces morbidity. The limits of intraoperative ‘permissive hypercapnia’ in CDH have not been established. It is also not know if the handling of CO2 differs during laparoscopy compared to thoracoscopy in neonates with CDH, as both cavities are effectively a single unit in these patients. High-frequency ventilation has been suggested by some as one means of intraoperative management of thoracoscopy in the CDH patient, with a few studies reporting on adequate outcome [11]. Only few studies addressed intraoperative hypercapnia and oxygenation in detail. Szavay et al. [12] retrospectively found no difference in maximum CO2 levels between open and MIS approaches. Other studies demonstrated differences in pH, but with little physiological effect. Most studies have however confirmed a significant intraoperative increase in CO2 excretion [13] and/or acidosis during thoracoscopic CDH repair. One randomised controlled pilot study has been performed looking at the effect of thoracoscopy in 10 neonates randomised to open and thoracoscopic repair. There was a significant intraoperative hypercapnia and acidosis in the thoracoscopic patients [14]. There are also concerns about the systemic effect of hypercapnia and on cerebral perfusion. Although neonatal piglets demonstrate efficient pulmonary auto-regulation during one-lung ventilation, the effects on cerebral perfusion has not been fully investigated. COCO2 levels may alter both cerebral blood flow and metabolism. It is therefore worth considering the effects of CO2 on cerebral metabolism and oxygenation even though there have been no documented adverse effects of CO2 insufflation during thoracoscopy in CDH patients. Only one study has investigated cerebral perfusion during thoracoscopy in neonates and showed a significant decrease in cerebral oxygenation during (from 87% ± 4% at the start to 75% ± 5% at end of operation) and after thoracoscopic CDH and oesophageal atresia repair [10], although the clinical effects of this is not known. It is also not known if the effect is directly secondary to systemic CO2 levels. This needs further research. One other concern about the thoracoscopic repair of CDH is recurrence. Possible explanations for higher recurrences during thoracoscopic approach include the acquisition of the learning curve for the procedure, the use of patch repair during thoracoscopy and the technical difficulties in achieving a complete diaphragmatic closure in these neonates. Many papers have quoted a higher recurrence rate after thoracoscopic repair of CDH [13], and after laparoscopic repair of Morgagni hernia. Tsao et al (Congenital Diaphragmatic Hernia Study Group) [15] reported on 4,390 infants limited to short-term recurrence during initial hospitalization. Of 151 MIS repairs, 12 recurred (7.9%) compared to 114 for open (2.7%), with a significant increased odds for recurrence (OR 3.59, 95% CI: 1.92–6.71) after adjusting for confounding factors. Infants that required a patch repair had a significantly higher recurrence rate (3.8% primary vs. 2.0% patch, p b 0.05). MIS repairs that used a patch had the highest recurrence rate at 8.8%. However, there was a significant increased odds of survival for infants undergoing MIS repairs (OR 5.57; 95% CI: 1.34–23.14). One systemic review of 3 eligible published series concluded that there is a higher incidence of recurrence with MIS (OR 3.2) but a non-significant trend to lower incidence of death (OR 0.33) [16].
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Not all report a higher recurrence rate however. Fishman et al. [17] found no clear difference in recurrence rate between approaches. Recurrence rates comparable with open surgery (as low as 3.6%) are reported. Some suggest an extracorporeal corner stitch, liberal prosthetic patch use, lower insufflation pressures and two experienced surgeons as means to decrease recurrence rates after thoracoscopy. There are similar incidence of complications between laparoscopic and thoracoscopic approaches. There may be selection criteria, including anatomical (stomach in the abdomen) and physiological (minimal ventilator support; peak inspiratory pressures in the low 20s), which allow safe MIS approach in these children. Oxygenation index (N3.0) has been shown as the only selection criteria significantly predictive of postoperative complications for thoracoscopic approach [18]. However, no randomised or even prospective data exist. 4.1. Best practice Most papers are retrospective case or cohort studies, with only one randomise pilot study. During thoracoscopic repair of CDH, both blood gases and ETCO2 should be closely monitored and correlated in these patients, especially when significant changes in ETCO2 are noted. While further studies are awaited on which further guidelines can be developed, careful selection [18], anaesthetic vigilance, monitoring and surveillance [10,13] and follow-up of these cases are required. Prospective, controlled and randomised studies on the outcome of thoracoscopic repair are needed to inform further practice. 5. Type of patch repair Patch repair of CDH is associated with an almost universally higher rate of recurrence than with primary repair; although this is not reported by some. The cause for increased recurrence after a patch repair can be technical, or related to the patch material. Studies have tried to identify any factors associated with the patch material itself. In patients requiring a patch repair, the three most common patch materials used are as follows: Gortex® (synthetic nonabsorbable polytetrafluoroethylene; PTFE), Surgisis® (non-cross-linked porcine intestine) and Permacol® (cross-linked porcine dermis). Others include AlloDerm® (acellular human cadaveric dermis), PTFE and polypropylene (Marlex®) and foetal bovine dermal collagen (Surgimend®). Tissue engineering is a fast developing area and may provide cellular scaffolding techniques which may prove advantageous in the future. The use of human biological scaffolding (allografts) may increase significantly with those developments. For now we concentrate on the commonly available xenografts and synthetic materials. There are no randomised controlled trials on type of patch repair in CDH patients. Most reports addressing this issue are retrospective cohort studies. Although there are a couple of randomised studies in animals suggest biological patches are associated with better integration to the chest wall, more muscle growth within the newly formed diaphragmatic tissue, this has not been proved in clinical practice. Despite the vast range of patch materials to choose from and the potential pros and cons between them, there are no type 1 or 2 evidence for choosing between non-biological and biological; and even within different biological materials. Type 4 (retrospective) studies exist. Some very small reports suggest better outcome with Permacol compared to Gore-Tex. However, Laituri et al. [19] found the incidence of small bowel obstruction (SBO) in patients with a nonabsorbable mesh was 17% and was associated with a 50% recurrence rate and 67% re-recurrence rate. Whereas Surgisis was associated with 19% incidence of SBO, a recurrence rate of 22% and a 50% re-recurrence rate. However, Alloderm® had significantly higher complications than both. Contrary to the above studies, Jawaid et al. [20] used Gore-Tex® patches in 35 and Surgisis® patches in 2 patients; both of the latter suffered early recurrences and were re-done using Gore-Tex®. Romao et al.
[21] found no difference in recurrence rate, adhesional obstruction or mortality between Surgisis and nonabsorbable synthetic (PTFE) in their series of 22 patients. They performed a meta-analysis along with the 2 other published papers and failed to show any difference in recurrence and SBO rates between the 2 materials. 5.1. Best practice There is no firm evidence in the literature to base a decision on. There seems to be the need for prospective controlled study to identify the best patch material for repair when needed. 6. Gastro-oesophageal disease Gastro-oesophageal reflux is seen in 50–90% of patients and should be treated by merit. Overall, however, the requirement for fundoplication is higher in the CDH population than in normal children. There may be factors which increase the need for fundoplication in CDH. However, motility of the oesophagus and the lower oesophageal sphincter tone seems unimpaired in survivors. Patch repair, presence of liver in the chest and need for ECMO have traditionally been cited as increasing the likelihood of needing fundoplication. Verbelen et al. [22] recently found that along with presence of liver in the chest, having FETO increases the risk of needing fundoplication. The rate of recurrence post fundoplication seems higher in CDH patients compared to normal children. Some retrospective reports suggest that fundoplication at the time of CDH repair decreased the incidence of growth failure. Guner et al. [23] selected 13 patients with anatomical abnormalities that would predispose to reflux and performed anterior fundoplication successfully, with 2 patients needing conversion to 360° fundoplication later in life; none of the 19 patients in their ‘control’ group needed fundoplication. It is proposed that routine fundoplication was only helpful in a sub group (liver up and patch) with predictable severe reflux. Only one study aimed to determine the value of routine fundoplication in a randomized patient-blinded prospective study of all patients having open repair [24]. The benefit of routine antireflux surgery (anterior hemi-fundoplication) at the time of repair of CDH was evaluated in 79 patients. At 6 months of age, there were less symptoms in the fundoplication group, but no perceived benefit of fundoplication beyond that time. There was no difference in the growth curve of fundoplication patients compared to control at any time. This probably represents the natural history of reflux, even within CDH. Therefore, they concluded that preventive antireflux surgery cannot be recommended as a standard procedure. 6.1. Best practice There is no firm evidence to suggest benefit from routine fundoplication based on the one randomised study done. There may be different need for fundoplication in patients with high risk factors, but no prospectively controlled study exists exploring this. 7. Long-term follow-up There are many multi-system and multi-disciplinary issues in CDH patients in the long term. Chronic lung disease is a common sequel in severely affected patients. Alveolar growth continues up to 8 years of age, and children can outgrow any mild restrictions to exercise tolerance and susceptibility to chest infections. An increased incidence of asthma is seen. Continued pulmonary hypertension into infancy and childhood are associated with poor outcome. There is a late mortality due to chronic lung disease and associated or secondary cardiac dysfunction, which can be as late as 4 years of age. Gastro-oesophageal reflux, feeding issues and poor growth are gastrointestinal/nutritional issues. Occasionally, these feeding issues
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need medical and/or surgical (feeding tubes/gastrostomies, fundoplication, etc.) management to improve outcome or quality of life. Surgical complications of intestinal adhesions and recurrent herniation can occur. Skeletal deformity secondary to chest wall deformity may need surgical correction later in life. Neurodevelopmental delay and hearing loss are nonsurgical complications, which are consequences of poor oxygenation, and are twice as common in children who receive ECMO support. The existence of intracerebral injuries and the classification of its severity are the major predictors of neurodevelopmental outcome. Other predictors of poor neurodevelopmental outcome are right sided CDH, liver up, need for patch and chronic lung disease. These neurodevelopmental and neurofunctional outcomes in children with congenital diaphragmatic hernia have encouraged the need for multi-disciplinary follow-up to both identify and manage these. Although there are no randomised studies to prove the clinical usefulness of multi-disciplinary follow-up, the impact of these have been established by good prospective studies of outcomes in this setting suggesting identification and management can aid at least some improvement [25]. These wide-ranging systemic morbidities, which can affect the CDH patient in the long term, need a variety of medical specialities involvement in their specific field, but with inter-specialty correlation in the overall care. Multi-disciplinary follow-up is required. This can take the form of visits to the different specialities involved in an individualised manner. But those requirements may also be best served by a multidisciplinary one-stop clinic. The Scottish Diaphragmatic Hernia Clinical Network (http://www. sdhcn.scot.nhs.uk/) and the Canadian Pediatric Surgery Network (http://www.capsnetwork.org/) are examples of networks working with the aims of producing multi-disciplinary guidelines for counselling, research, development and follow-up in patients with CDH. Key guidelines: • Antenatal US can be used to help prognosticate postoperative outcome if uniformity in measuring and reporting are used. • The use of observed to expected antenatal measurements is preferred as they give more specific and accurate information • Antenatal intervention in the group of patients with worst outcome should be part of ongoing clinical trials with good follow-up and reporting of outcome. • Thoracoscopic approach to CDH should be done by those with sufficient MIS experience, with close liaison with anaesthetic colleagues for patient selection, anaesthetic vigilance, monitoring and surveillance and follow-up. • Regular monitoring of intraoperative blood gases and ETCO2 is necessary (1 randomised controlled pilot study demonstration decreased pH and herpercapnia). Use of routine regional oxygenation (especially cerebral) should be considered, both for clinical correlation and outcome and for research. • There is no clear evidence with regard to the best results in those requiring a patch. • Routine fundoplication at the time of CDH repair is not supported by the evidence of 1 randomised controlled study. • Multi-disciplinary follow-up is required, and may be suited for a multi-disciplinary one-stop clinic. Research directions: • Antenatal classification of disease severity needs research into the standardisation of methodology to predict outcome and guide intervention. Intervention should probably continue as part of a randomised trials for research and development. • The safety, intraoperative management and outcome from thoracoscopic surgery need both laboratory and clinical based research to clarify the issues around acidosis and oxygenation. Randomised trials are needed to help with the best approach for surgical management. • Biological advances and tissue engineering focusing on the
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development of biological diaphragmatic tissue replacement in those needing patching, to minimise recurrence and complications. Conflict of interest statement There are no financial and personal relationships with other people or organizations that could inappropriately influence this work to disclose. References [1] Harrison MR, Keller RL, Hawgood SB, Kitterman JA, Sandberg PL, Farmer DL, et al. A randomized trial of fetal endoscopic tracheal occlusion for severe fetal congenital diaphragmatic hernia. N Engl J Med November 13 2003;349(20):1916–24. [2] Jani JC, Peralta CF, Nicolaides KH. Lung-to-head ratio: a need to unify the technique. Ultrasound Obstet Gynecol January 2012;39(1):2–6. [3] Peralta CF, Cavoretto P, Csapo B, Vandecruys H, Nicolaides KH. Assessment of lung area in normal fetuses at 12-32 weeks. Ultrasound Obstet Gynecol December 2005;26(7):718–24. [4] Jani J, Nicolaides KH, Keller RL, Benachi A, Peralta CF, Favre R, et al. Observed to expected lung area to head circumference ratio in the prediction of survival in fetuses with isolated diaphragmatic hernia. Ultrasound Obstet Gynecol July 2007;30(1): 67–71. [5] Walsh DS, Hubbard AM, Olutoye OO, Howell LJ, Crombleholme TM, Flake AW, et al. Assessment of fetal lung volumes and liver herniation with magnetic resonance imaging in congenital diaphragmatic hernia. Am J Obstet Gynecol November 2000; 183(5):1067–9. [6] Bebbington M, Victoria T, Danzer E, Moldenhauer J, Khalek N, Johnson M, et al. Comparison of ultrasound and magnetic resonance imaging parameters in predicting survival in isolated left-sided congenital diaphragmatic hernia. Ultrasound Obstet Gynecol December 4 2013;43(6):670–4. [7] Ruano R, Yoshisaki CT, da Silva MM, Ceccon ME, Grasi MS, Tannuri U, et al. A randomized controlled trial of fetal endoscopic tracheal occlusion versus postnatal management of severe isolated congenital diaphragmatic hernia. Ultrasound Obstet Gynecol January 2012;39(1):20–7. [8] Jani JC, Nicolaides KH, Gratacos E, Valencia CM, Done E, Martinez JM, et al. Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion. Ultrasound Obstet Gynecol September 2009;34(3):304–10. [9] Pacilli M, Pierro A, Kingsley C, Curry JI, Herod J, Eaton S. Absorption of carbon dioxide during laparoscopy in children measured using a novel mass spectrometric technique. Br J Anaesth August 2006;97(2):215–9. [10] Bishay M, Giacomello L, Retrosi G, Thyoka M, Nah SA, McHoney M, et al. Decreased cerebral oxygen saturation during thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia in infants. J Pediatr Surg January 2011;46(1):47–51. [11] Mortellaro VE, Fike FB, Adibe OO, Juang D, Aguayo P, Ostlie DJ, et al. The use of highfrequency oscillating ventilation to facilitate stability during neonatal thoracoscopic operations. J Laparoendosc Adv Surg Tech A November 2011;21(9):877–9. [12] Szavay PO, Obermayr F, Maas C, Luenig H, Blumenstock G, Fuchs J. Perioperative outcome of patients with congenital diaphragmatic hernia undergoing open versus minimally invasive surgery. J Laparoendosc Adv Surg Tech A April 2012;22(3): 285–9. [13] McHoney M, Giacomello L, Nah SA, De CP, Kiely EM, Curry JI, et al. Thoracoscopic repair of congenital diaphragmatic hernia: intraoperative ventilation and recurrence. J Pediatr Surg February 2010;45(2):355–9. [14] Bishay M, Giacomello L, Retrosi G, Thyoka M, Garriboli M, Brierley J, et al. Hypercapnia and acidosis during open and thoracoscopic repair of congenital diaphragmatic hernia and esophageal atresia: results of a pilot randomized controlled trial. Ann Surg December 2013;258(6):895–900. [15] Tsao K, Lally PA, Lally KP. Minimally invasive repair of congenital diaphragmatic hernia. J Pediatr Surg June 2011;46(6):1158–64. [16] Lansdale N, Alam S, Losty PD, Jesudason EC. Neonatal endosurgical congenital diaphragmatic hernia repair: a systematic review and meta-analysis. Ann Surg July 2010;252(1):20–6. [17] Fishman JR, Blackburn SC, Jones NJ, Madden N, De CD, Haddad MJ, et al. Does thoracoscopic congenital diaphragmatic hernia repair cause a significant intraoperative acidosis when compared to an open abdominal approach? J Pediatr Surg March 2011;46(3):458–61. [18] Gomes FC, Kuhn P, Lacreuse I, Kasleas C, Philippe P, Podevin G, et al. Congenital diaphragmatic hernia: an evaluation of risk factors for failure of thoracoscopic primary repair in neonates. J Pediatr Surg March 2013;48(3):488–95. [19] Laituri CA, Garey CL, Valusek PA, Fike FB, Kaye AJ, Ostlie DJ, et al. Outcome of congenital diaphragmatic hernia repair depending on patch type. Eur J Pediatr Surg November 2010;20(6):363–5. [20] Jawaid WB, Qasem E, Jones MO, Shaw NJ, Losty PD. Outcomes following prosthetic patch repair in newborns with congenital diaphragmatic hernia. Br J Surg December 2013;100(13):1833–7. [21] Romao RL, Nasr A, Chiu PP, Langer JC. What is the best prosthetic material for patch repair of congenital diaphragmatic hernia? Comparison and meta-analysis of porcine small intestinal submucosa and polytetrafluoroethylene. J Pediatr Surg August 2012;47(8):1496–500. [22] Verbelen T, Lerut T, Coosemans W, De LP, Nafteux P, Van RD, et al. Antireflux surgery after congenital diaphragmatic hernia repair: a plea for a tailored approach. Eur J Cardiothorac Surg August 2013;44(2):263–7.
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[23] Guner YS, Elliott S, Marr CC, Greenholz SK. Anterior fundoplication at the time of congenital diaphragmatic hernia repair. Pediatr Surg Int August 2009; 25(8):715–8. [24] Maier S, Zahn K, Wessel LM, Schaible T, Brade J, Reinshagen K. Preventive antireflux surgery in neonates with congenital diaphragmatic hernia: a single-blinded prospective study. J Pediatr Surg August 2011;46(8):1510–5.
[25] Danzer E, Gerdes M, D'Agostino JA, Hoffman C, Bernbaum J, Bebbington MW, et al. Longitudinal neurodevelopmental and neuromotor outcome in congenital diaphragmatic hernia patients in the first 3 years of life. J Perinatol November 2013;33(11): 893–8.
