- Email: [email protected]
Surgical management of neonates with congenital diaphragmatic hernia
Seminars in Pediatric Surgery (2007) 16, 109-114
Surgical management of neonates with congenital diaphragmatic hernia Matthew T. Harting, MD, Kevin P. Lally, MD From the Division of Pediatric Surgery, Department of Surgery, University of Texas Medical School, Houston, Texas. KEYWORDS Congenital diaphragmatic hernia; Surgery; Extracorporeal membrane oxygenation; Neonate
Congenital diaphragmatic hernia (CDH) is one of the most challenging and complex pediatric abnormalities to manage, both medically and surgically. The care of these neonates has seen significant evolution, from previous aggressive ventilation and emergent operation to current permissive hypercapnea, physiologic stabilization, and elective surgical repair, all in less than two decades. These changes have led to many centers reporting survival rates near 80%, a dramatic improvement from the 50% survival reported in the 1970s. This review covers the current principles guiding the surgical management of CDH in the neonate, including preoperative stabilization, operative timing, extracorporeal membrane oxygenation, surgical approach, and management of recurrence. Although many clinical challenges remain, multi-institutional collaboration and ongoing research efforts will hopefully improve the clinical care of these patients. © 2007 Elsevier Inc. All rights reserved.
History of surgical management Although diaphragmatic hernia was initially described by Ambrose Pare in the late 16th century, and the first published case of congenital diaphragmatic hernia in a child appeared in the early 18th century, the first report of a successful surgical repair was not until the early 20th century.1 Nearly 25 years later, Hedblom published a large series of patients who underwent surgical repair for diaphragmatic hernia, concluding that early surgery would improve survival.2 In 1940, Ladd and Gross stressed the importance of early surgical therapy for CDH patients.3 The urgency seemed appropriate, given the fact that the bowel was pressing the lung and the heart, creating a situation similar to a tension pneumothorax. They felt that the strategy of waiting was “apparently responsible for the loss of a
Address reprint requests and correspondence: Kevin P. Lally, MD, University of Texas Medical School, Houston, 6431 Fannin St., MSB 5.258, Houston, TX 77030. E-mail: [email protected].
1055-8586/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2007.01.007
great many lives” and concluded that a “policy of delaying operation until the infant is older is a dangerous one.” It’s also important to remember that these initial surgical endeavors were forged in an era with no neonatal intensive care units, no mechanical ventilation, and a support staff unfamiliar with CDH management. Ladd and Gross also noted the importance of reaching a hospital appropriately equipped to handle such a case. In 1946, Gross reported the first successful CDH repair in a neonate less than 24 hours old.4
Operative timing Although considered a surgical emergency from the 1940s3 through the 1980s,5 CDH is currently managed with cardiopulmonary stabilization, followed by definitive surgical repair. The paradigm shift from emergent to delayed repair occurred in 1987, when Sakai and coworkers showed that respiratory system compliance frequently deteriorates after CDH repair.6 Their report identified multiple factors, including distortion of the repaired diaphragm, increased in-
110 traabdominal pressure, and the hypoplastic ipsilateral lung, that frequently lead to a rapid decline in compliance after emergent surgery. They recommended that repair should be deferred until after initial resuscitation improves physiologic function, achieving a period of cardiorespiratory stability. The initial report by Sakai was followed by several other studies evaluating early versus delayed surgical repair.7-9 Most of these concluded that there was no difference in mortality and extracorporeal membrane oxygenation (ECMO) use, irrespective of surgical timing. There were two randomized trials which compared early repair (less than 12 hours of age) with delayed repair (after 24 hours9 or after 96 hours8), and neither identified a statistically significant difference in mortality. Although surgical modifications may be partially responsible for the improved overall survival over the last 20 years, concomitant advances in ventilatory strategies have certainly played a major role in minimizing mortality. Even though the current routine in most centers includes nonemergent surgery, there is no clear evidence to support delayed versus immediate surgical repair.10
Pre-operative stabilization Optimal initial postnatal resuscitation and management is aimed toward minimizing the physiologic derangements associated with pulmonary hypoplasia and pulmonary hypertension. Following delivery (or postnatal diagnosis of CDH), prompt endotracheal intubation (without high-pressure bag ventilation), nasogastric tube placement, and arterial/venous catheter placement are important initial maneuvers for pulmonary and hemodynamic support.11 Oxygenation and acid-base status should be closely monitored. An infant is considered ready for operation once they are hemodynamically stable, have reached an acid-base status within the normal physiologic range, and are able to tolerate conventional ventilation, while maintaining adequate oxygenation.11,12 Clear, objective, universal criteria to define physiologic stabilization have not been accepted, therefore leaving each center to determine the methods and endpoints of preoperative stabilization. General guidelines include minimal ventilatory support, resolution of pulmonary hypertension, improvement in pulmonary compliance, and resolving pulmonary radiographic abnormalities.10,13 There are exceptions to these indications, such as patients requiring ECMO, and these are addressed below. Some infants stabilize quickly and can undergo repair within 48 hours of birth, whereas others may require weeks of medical management before operation. Irrespective of the preoperative delay, the key principle is that initial morbidity is the result of pulmonary hypoplasia and pulmonary hypertension; management requires a delicate balance of hemodynamic stabilization, permissive hypercapnea, and respiratory support while minimizing iatrogenic pulmonary injury.11 The
Seminars in Pediatric Surgery, Vol 16, No 2, May 2007 precise length or endpoint of stabilization, as discussed earlier, remains unclear.10
Extracorporeal membrane oxygenation In the late 1970s, the first reports of ECMO for infants with CDH14 provided a potential therapy for these children with severely hypoplastic lungs. Since that time, the strategy for ECMO has undergone continual refinement and critical examination. Approximately one-third of infants born with CDH will be treated with ECMO during their initial course of management.15,16 The previously accepted indications for initiation of ECMO include an Oxygenation Index (OI) ⬎40, PaCO2 consistently ⬎12, and an A-a gradient consistently ⬎600 mmHg.11,12,17 The most common indication for ECMO in the infant with CDH today is “failure to respond.” Most centers have established criteria that limit the allowable positive pressure on the ventilator. When the patient requires more than a set level of support, ECMO is utilized rather than escalating the amount of positive pressure ventilation. An OI ⬎40 is much less frequently used as an indication for ECMO in patients with CDH. In addition, the presence of an intracranial hemorrhage ⬎Grade I, gestational age ⬍34 weeks, significant additional congenital abnormalities, or lethal chromosomal abnormalities should preclude initiation of ECMO. Among infants where conventional medical therapy fails to maintain oxygenation or normal acid-base status, ECMO should be considered. Although ECMO was initially utilized postoperatively,18 the trend toward preoperative use, often extending through surgery, has coincided with the trend of preoperative stabilization.19 ECMO has become one of the management options for respiratory failure during preoperative stabilization. ECMO for pre-repair stabilization was popularized in the late 1980s, as the management paradigm shifted from emergent surgery. Early reports of stabilization and subsequent repair on ECMO highlighted the benefit of ECMO before delayed repair, particularly among high-risk infants.20,21 One group compared infants treated without ECMO to infants stabilized on ECMO before repair and found an improvement in overall survival from 43% to 67% (P ⬍ 0.05).21 In 2002, the CDH Study Group reported that 85% of infants requiring ECMO had support initiated pre-repair.22 Of patients placed on ECMO pre-repair, 54% underwent repair while on ECMO and 29% underwent repair after decannulation, leaving 16% that were never repaired. Infants that underwent repair on ECMO had a 50% mortality, whereas those that underwent repair after ECMO had a 17% mortality. The majority of patients requiring support were placed on ECMO in the first 24 hours of life. A large proportion of patients placed on ECMO preoperatively undergo repair while on ECMO.19 In 1998, the CDH Study Group reported that 19% of all CDH repairs
Harting and Lally
Surgical Management of CDH
were performed while on ECMO and 33% of patients placed on ECMO underwent repair on ECMO.13 As hemorrhage is a known complication among infants requiring ECMO,23 several centers have studied strategies to decrease bleeding and report minimal hemorrhagic complications.24,25 The use of aminocaproic acid (Amicar®), an inhibitor of fibrinolysis, was initially reported in 1990 in an attempt to limit intracranial hemorrhage (ICH).26 A pilot study showed that Amicar® decreased the incidence of ICH and other hemorrhagic complications, while inciting minimal thrombotic complications.27 A subsequent multicenter, prospective, randomized trial of 29 infants found that Amicar® was safe, but there was no difference in hemorrhagic complications, including ICH, between the treatment and placebo groups.28 Of note, CDH patients were excluded from this study. Downard and colleagues followed up their pilot study with a recent review of their use of Amicar® in high-risk patients over the last 10 years.15 They defined high-risk patients as those with an increased likelihood of hemorrhage secondary to preexisting or anticipated surgical procedure, severe hypoxia/acidosis, prematurity, prior ICH, or profound, uncorrectable coagulopathy. They compared patients receiving Amicar® at their institution with similar patients in an ECMO registry. Although they did not identify a statistically significant difference in mortality or ICH between the two groups, the rate of surgical site bleeding was significantly reduced in the Amicar® group (P ⫽ 0.005). It has become routine to use Amicar® when patients require surgical repair on ECMO if there are no contraindications.
Surgical approach and principles The traditional approach to repair of the diaphragmatic defect is via a subcostal incision on the ipsilateral side of the hernia. More than 90% of surgeons use this incision, whereas only 6% prefer the thoracic approach.13 After reduction of the abdominal viscera from the thorax and evisceration of the bowel to achieve adequate exposure, a true hernia sac (present only 10-20% of the time) should be identified and excised. Depending on the size of the defect, there are three general operative strategies. If the defect is small, it should be closed primarily with nonabsorbable suture. If the defect is relatively large, attempted primary closure may leave the patient with a flattened diaphragm and inferior pulmonary compliance. Alternatively, a prosthetic patch [such as polytetrafluoroethylene (PTFE), the most commonly used prosthetic material13] can be tailored to restore a more natural, tension-free diaphragm shape. Many types of patch closure, from muscle flaps to bioactive prosthetic materials, have been described (Table 1). The disadvantage with the use of a synthetic material is lack of material growth, leading to hernia recurrence in nearly 50% of patients.29 In an effort to prevent the recurrent hernia, specialized techniques have been developed and reported. Loff and colleagues described the use of a cone-shaped,
111 Table 1
Repair options for large defects13
Prosthetic materials: Polytetrafluoroethylene (PTFE) (Gore-Tex) Polypropylene (Marlex) Dacron Muscle flaps: Abdominal42 Latissimus dorsi43 Latissimus dorsi and serratus anterior32 Bioactive Materials: Surgisis44
double-fixed PTFE patch that reduced their recurrences (within the first year after repair) from 46% to 9%.30 The cone shape increased abdominal capacity and created a more physiologic diaphragm, and the double fixation improved the overall stability. Fuchs and associates developed an autologous tendon engineered from mesenchymal amniocytes in an ovine model.31 They found that when the cellular construct was used for diaphragmatic repair, the lambs experienced improved mechanical and functional outcomes when compared with an equivalent acellular bioprosthetic repair. Developments in cellular-based therapies hold promise in developing tissue that could grow with the patient. For very large defects (or agenesis of the diaphragm), the posterior rim of the diaphragm, as well as the medial component, may be absent. To handle this more challenging repair, the prosthetic patch should be secured to the abdominal wall or to the ribs. Securing the patch medially may be especially difficult. These patients, who require a large patch, will have a recurrence nearly 100% of the time, as the synthetic material does not grow with the child. The initial repair in these patients should be considered the first operation of a staged procedure. Case reports of the use of reverse latissimus dorsi and serratus anterior muscle flaps hold promise in these difficult cases, as the native tissue may offer the advantage of continued growth of the reconstructed diaphragm.32 If closure of the abdominal fascia is likely to increase intraabdominal pressure enough to exacerbate the respiratory compromise, the fascia should be left open. Infants who require ECMO before CDH repair are more likely to have abdominal wall closure problems secondary to loss of abdominal domain.33 Coverage may then be achieved via skin closure, creation of a Silo, or abdominoplasty.34 Schnitzer and colleagues advocated suturing a Vicryl mesh patch to the fascial edges before skin closure. They felt that this would serve as an additional protective barrier and help to clarify the dissection during the subsequent definitive closure.33 For infants repaired on ECMO, or infants likely to require postoperative ECMO, special considerations are warranted. Fibrin or thrombin sealants should be considered to reduce the chance of suture line hemorrhage. The use of Amicar®, as discussed above, may prevent hemorrhagic
112
Seminars in Pediatric Surgery, Vol 16, No 2, May 2007 lator support (PIP ⬍24), and no evidence of pulmonary hypertension. They found thoracoscopic primary repair to be safe, feasible, and comparable to open repair in their seven patients, although one patient developed a recurrence.
Recurrent diaphragmatic hernia
Figure 1 Operative positioning for the minimally invasive approach to a Morgagni hernia: Modified Fowler position. (Reprinted with permission.36)
complications. Very careful inspection of the operative field for hemostasis on completion of the case is paramount. Tube thoracostomy is infrequently indicated,35 but occasionally necessary for draining significant hemorrhage,11 uncontrolled air leak,11 chylothorax, pneumothorax, or a large pleural effusion. Tube thoracostomy is postulated to cause contra- and ipsilateral iatrogenic pulmonary injury via mediastinal shift after pleural suction and, therefore, has fallen out of favor unless necessary. Usually, the lungs will gradually displace fluid and air as they enlarge.
Changes in the medical and surgical management have improved survival and, consequently, have exposed previously uncommon additional morbidity. Recurrence of the diaphragmatic defect is one such complication. Prevention of recurrent herniation requires that the reconstructed diaphragm grow with the patient. This growth is dependent on cellular deposition, proliferation, and organization into tissue. Such tissue organization requires vascular supply. Current theory, given the location of the diaphragm, is that limited growth of the reconstructed diaphragm is secondary to lack of vessel formation and in-growth. The overall rate of recurrence in most published series ranges from 14% to 22%.21,38,39 It is impossible to compare or generalize the few studies given the retrospective designs, lack of standardization of defect severity, highly variable repair strategy, and inconsistent follow-up. There are several factors likely associated with increased risk of recurrence. Hajer and coworkers had a 14% incidence of recurrence and identified a right-sided defect, a large defect, a patch closure, and the use of ECMO as four factors that lead to a statistically significant increase in recurrence.38 Moss and coworkers examined patch durability and noted a 41% recurrence,29 nearly identical to the 42% recurrence with patch repairs that Hajer and coworkers
Minimally invasive surgery Advances in minimally invasive surgery (MIS) have led to both thoracoscopic and laparoscopic repairs of CDH. Arca and coworkers described the technical development of their minimally invasive approach to 15 children.36 They found laparoscopy to be a better approach to Morgagni defects (Figure 1) and thoracoscopy a better approach to Bochdalek defects (Figure 2). They concluded that MIS was ideal for Morgagni defects, but that Bochdalek repair (via thoracoscopy) should be approached cautiously based on their high failure rate (14%), prohibitive increases in PCO2, and acidemia.36 Subsequently, Yang and colleagues formulated preoperative patient selection criteria to maximize successful thoracoscopic diaphragm repair.37 Preoperative requirements included an intraabdominal stomach, minimal venti-
Figure 2 Minimally invasive approach to Bochdalek defects. (A) Operative positioning for a Bochdalek hernia. The infant should be placed left side up about 45° from the horizontal with a slight reverse Trendelenburg position. (B) Port placement for thoracoscopic Bochdalek hernia repair. (Reprinted with permission.36)
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Surgical Management of CDH
reported. Because most very large defects require patch repair, it is difficult to isolate the critical factor. A missed hernia sac is sometimes identified in patients that recur,38,39 causing it to be associated with increased risk for recurrence as well. Hajer and coworkers reported an average latency of 4 months (0.2-6.9 months),38 and Slatzman and colleagues reported an average of 8 months latency (2-16 months)40 between surgery and recurrence. Late recurrences are uncommon. Recurrent hernias can present with respiratory (dyspnea) or gastrointestinal symptoms, and can usually be confirmed via chest x-ray. Moss and colleagues identified second recurrences or re-recurrences in 25% of their patients that experienced recurrence.29 There is limited evidence evaluating the optimal timing for repair after recurrence. Some surgeons proceed with prompt repair, minimizing the risk of incarceration. However, early repair in a newborn could be high risk and, therefore, the surgeon may opt for delay with close follow up, particularly if the patient is without serious symptoms secondary to the re-herniation. If the risks of the operation outweigh the benefits of immediate repair, close monitoring, including routine physical examination and chest radiography, is paramount. Some surgeons choose to approach the re-repair via the chest, especially if the primary repair was approached through the abdomen. No study has compared the thoracic versus the abdominal approach. On rare occasion, exposure from the chest and the abdomen is required. As with the primary procedure, the guiding principle of re-repair is to reduce the abdominal contents and close the defect. This may be accomplished in a primary fashion or frequently will require additional patch placement. Saltzman reported five successful repairs using a novel hernia plug approach, where a polypropylene mesh plug was placed in the defect via an anterolateral thoracotomy.40 Bianchi reported three successful repairs using a reverse latissimus dorsi muscle flap.41 As a broad, thin, well-vascularized sheet of muscle, the latissimus dorsi was found to be well suited to replace the entire hemidiaphragm. Although they reported its use for recurrence, they recommended considering its use at the primary operation if insufficient tissue was available.
Conclusion The management of CDH has seen steady progress over the last 20 years. Today, overall survival has reached 80% in live-born infants as a direct result of changes in medical and surgical management. Preoperative physiologic stabilization and subsequent elective repair have become the cornerstones of management. In many centers, ECMO is a key component of stabilization. Although elective repair has become routine, optimal timing of operation remains unclear. The role of minimally invasive surgery is undefined,
113 but instrumentation and techniques continue to improve. Although recurrent herniation remains high, ongoing research is focused on the development of new materials and new techniques to allow the diaphragm to grow with the patient. With burgeoning alternative medical and surgical strategies, novel clinical and basic science research, and multi-institutional cooperation, management of these patients is certain to continue to evolve.
References 1. Puri P, Wester T. Historical aspects of congenital diaphragmatic hernia. Pediatr Surg Int 1997;12:95-100. 2. Hedblom CA. Diaphragmatic hernia: a study of three hundred and seventy eight cases in which operation was performed. J Am Med Assoc 1925;85:547-53. 3. Ladd WE, Gross RE. Congenital diaphragmatic hernia. N Eng J Med 1940;223:917-25. 4. Gross RE. Congenital hernia of the diaphragm. Am J Dis Child 1946;71:579-92. 5. Firor HV. Surgical emergencies in newborns and infants. Surg Clin North Am 1972;52:77-98. 6. Sakai H, Tamura M, Hosokawa Y, et al. Effect of surgical repair on respiratory mechanics in congenital diaphragmatic hernia. J Pediatr 1987;111:432-8. 7. Langer JC, Filler RM, Bohn DJ, et al. Timing of surgery for congenital diaphragmatic hernia: is emergency operation necessary? J Pediatr Surg 1988;23:713-34. 8. Nio M, Haase G, Kennaugh J, et al. A prospective trial of delayed versus immediate repair of congenital diaphragmatic hernia. J Pediatr Surg 1994;29:618-21. 9. de la Hunt MN, Madden N, Scott JES, et al. Is delayed surgery really better for congenital diaphragmatic hernia? A prospective, randomized clinical trial. J Pediatr Surg 1996;31:1554-6. 10. Moyer V, Moya F, Tibboel R, et al. Late versus early surgical correction for congenital diaphragmatic hernia in newborn infants. Cochrane Database Syst Rev 2000;3:CD001695. 11. Skarsgard ED, Harrison MR. Congenital diaphragmatic hernia: the surgeon’s perspective. Pediatr Rev 1999;20:e71-8. 12. Hedrick HL. Evaluation and management of congenital diaphragmatic hernia. Pediatr Case Rev 2001;1:25-36. 13. Clark RH, Hardin WD, Hirschl RB, et al. Current surgical management of congenital diaphragmatic hernia: a report from the Congenital Diaphragmatic Hernia Study Group. J Pediatr Surg 1998;33:1004-9. 14. German JC, Gazzaniga AB, Amlie R, et al. Management of pulmonary insufficiency in diaphragmatic hernia using extracorporeal circulation with a membrane oxygenator (ECMO). J Pediatr Surg 1977;12:905-12. 15. Downard CD, Betit P, Chang RW, et al. Impact of Amicar on hemorrhagic complications of ECMO: a ten-year review. J Pediatr Surg 2003;38:1212-6. 16. Sreenan C, Etches P, Osiovich H, et al. The western Canadian experience with congenital diaphragmatic hernia: perinatal factors predictive of extracorporeal membrane oxygenation and death. Pediatr Surg Int 2001;17:196-200. 17. Lally KP. Extracorporeal membrane oxygenation in patients with congenital diaphragmatic hernia. Semin Pediatr Surg 1996;5:249-55. 18. Langham MR Jr, Krummel TM, Greenfield LJ, et al. Extracorporeal membrane oxygenation following repair of congenital diaphragmatic hernias. Ann Thorac Surg 1987;44:247-52. 19. Davis PJ, Firmin RK, Manktelow B, et al. Long-term outcome following extracorporeal membrane oxygenation for congenital diaphragmatic hernia: the UK experience. J Pediatr 2004;144:309-15. 20. Lally KP, Paranka MS, Roden J, et al. Congenital diaphragmatic hernia. Stabilization and repair on ECMO. Ann Surg 1992;216:569-73.
114 21. West KW, Bengston K, Rescorla FJ, et al. Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia. Ann Surg 1992;216:454-60. 22. Lally KP, CDH Study Group. The use of ECMO for stabilization of infants with congenital diaphragmatic hernia, 2002. American Academy of Pediatrics, Surgical Section. 2002 (Abstract) 23. Vazquez WD, Cheu HW. Hemorrhagic complications and repair of congenital diaphragmatic hernias: does timing of the repair make a difference? Data from the Extracorporeal Life Support Organization. J Pediatr Surg 1994;29:1002-5. 24. Austin MT, Lovvorn HN 3rd, Feurer ID, et al. Congenital diaphragmatic hernia repair on extracorporeal life support: a decade of lessons learned. Am Surg 2004;70:389-95. 25. Wilson JM, Bower LK, Lund DP. Evolution of the technique of congenital diaphragmatic hernia repair on ECMO. J Pediatr Surg 1994;29:1109-12. 26. Ackerman N, Lyon J, Ratner I, et al. A proposal for a multicenter trial of 6-amino-hexanoic acid (AMICAR) for the prevention of bleeding of infants on ECMO. Presented at the 2nd Annual ELSO meeting, Ann Arbor, MI, 1990. 27. Wilson JM, Bower LK, Fackler JC, et al. Aminocaproic acid decreases the incidence of intracranial hemorrhage and other hemorrhagic complications of ECMO. J Pediatr Surg 1993;28:536-41. 28. Horwitz JR, Cofer BR, Warner BW, et al. A multicenter trial of 6-Aminocaproic Acid (Amicar) in the prevention of bleeding in infants on ECMO. J Pediatr Surg 1998;33:1610-3. 29. Moss RL, Chen CM, Harrison MR. Prosthetic patch durability in congenital diaphragmatic hernia: a long-term follow-up study. J Pediatr Surg 2001;36:152-4. 30. Loff S, Wirth H, Jester I, et al. Implantation of a cone-shaped doublefixed patch increases abdominal space and prevents recurrence of large defects in congenital diaphragmatic hernia. J Pediatr Surg 2005;40: 1701-5. 31. Fuchs JR, Kaviani A, Oh JT, et al. Diaphragmatic reconstruction with autologous tendon engineered from mesenchymal amniocytes. J Pediatr Surg 2004;39:834-838.
Seminars in Pediatric Surgery, Vol 16, No 2, May 2007 32. Samarakkody U, Klaassen M, Nye B. Reconstruction of congenital agenesis of the hemidiaphragm by combined reverse latissimus dorsi and serratus anterior muscle flaps. J Pediatr Surg 2001;36:1637-40. 33. Schitzer JJ, Kikiros CS, Short BL, et al. Experience with abdominal wall closure for patients with congenital diaphragmatic hernia repaired on ECMO. J Pediatr Surg 1995;30:19-22. 34. Conforti AF, Losty PD. Perinatal management of congenital diaphragmatic hernia. Early Hum Dev 2006;82:283-7. 35. Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995;30:406-9. 36. Arca MJ, Barnhart DC, Lelli JL Jr, et al. Early experience with minimally invasive repair of congenital diaphragmatic hernias: results and lessons learned. J Pediatr Surg 2003;38:1563-8. 37. Yang EY, Allmendinger N, Johnson SM, et al. Neonatal thoracoscopic repair of congenital diaphragmatic hernia: selection criteria for successful outcome. J Pediatr Surg 2005;40:1369-75. 38. Hajer GF, vd Staak FH, de Haan AF, et al. Recurrent congenital diaphragmatic hernia; Which factors are involved? Eur J Pediatr Surg 1998;8:329-33. 39. Rowe DH, Stolar CJ. Recurrent diaphragmatic hernia. Semin Pediatr Surg 2003;12:107-9. 40. Saltzman DA, Ennis JS, Mehall JR, et al. Recurrent congenital diaphragmatic hernia: a novel repair. J Pediatr Surg 2001;36:1768-9. 41. Bianchi A, Doig CM, Cohen SJ. The reverse latissimus dorsi flap for congenital diaphragmatic hernia repair. J Pediatr Surg 1983;18: 560-3. 42. Joshi SB, Sen S, Chacko J, et al. Abdominal muscle flap repair for large defects of the diaphragm. Pediatr Surg Int 2005;21:677-80. 43. Sydorak RM, Hoffman W, Lee H, et al. Reversed latissimus dorsi muscle flap for repair of recurrent congenital diaphragmatic hernia. J Pediatr Surg 2003;38:296-300. 44. Grethel EJ, Cortes RA, Wagner AJ, et al. Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex. J Pediatr Surg 2006;41:29-33.
Surgical management of neonates with congenital diaphragmatic hernia Matthew T. Harting, MD, Kevin P. Lally, MD From the Division of Pediatric Surgery, Department of Surgery, University of Texas Medical School, Houston, Texas. KEYWORDS Congenital diaphragmatic hernia; Surgery; Extracorporeal membrane oxygenation; Neonate
Congenital diaphragmatic hernia (CDH) is one of the most challenging and complex pediatric abnormalities to manage, both medically and surgically. The care of these neonates has seen significant evolution, from previous aggressive ventilation and emergent operation to current permissive hypercapnea, physiologic stabilization, and elective surgical repair, all in less than two decades. These changes have led to many centers reporting survival rates near 80%, a dramatic improvement from the 50% survival reported in the 1970s. This review covers the current principles guiding the surgical management of CDH in the neonate, including preoperative stabilization, operative timing, extracorporeal membrane oxygenation, surgical approach, and management of recurrence. Although many clinical challenges remain, multi-institutional collaboration and ongoing research efforts will hopefully improve the clinical care of these patients. © 2007 Elsevier Inc. All rights reserved.
History of surgical management Although diaphragmatic hernia was initially described by Ambrose Pare in the late 16th century, and the first published case of congenital diaphragmatic hernia in a child appeared in the early 18th century, the first report of a successful surgical repair was not until the early 20th century.1 Nearly 25 years later, Hedblom published a large series of patients who underwent surgical repair for diaphragmatic hernia, concluding that early surgery would improve survival.2 In 1940, Ladd and Gross stressed the importance of early surgical therapy for CDH patients.3 The urgency seemed appropriate, given the fact that the bowel was pressing the lung and the heart, creating a situation similar to a tension pneumothorax. They felt that the strategy of waiting was “apparently responsible for the loss of a
Address reprint requests and correspondence: Kevin P. Lally, MD, University of Texas Medical School, Houston, 6431 Fannin St., MSB 5.258, Houston, TX 77030. E-mail: [email protected].
1055-8586/$ -see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1053/j.sempedsurg.2007.01.007
great many lives” and concluded that a “policy of delaying operation until the infant is older is a dangerous one.” It’s also important to remember that these initial surgical endeavors were forged in an era with no neonatal intensive care units, no mechanical ventilation, and a support staff unfamiliar with CDH management. Ladd and Gross also noted the importance of reaching a hospital appropriately equipped to handle such a case. In 1946, Gross reported the first successful CDH repair in a neonate less than 24 hours old.4
Operative timing Although considered a surgical emergency from the 1940s3 through the 1980s,5 CDH is currently managed with cardiopulmonary stabilization, followed by definitive surgical repair. The paradigm shift from emergent to delayed repair occurred in 1987, when Sakai and coworkers showed that respiratory system compliance frequently deteriorates after CDH repair.6 Their report identified multiple factors, including distortion of the repaired diaphragm, increased in-
110 traabdominal pressure, and the hypoplastic ipsilateral lung, that frequently lead to a rapid decline in compliance after emergent surgery. They recommended that repair should be deferred until after initial resuscitation improves physiologic function, achieving a period of cardiorespiratory stability. The initial report by Sakai was followed by several other studies evaluating early versus delayed surgical repair.7-9 Most of these concluded that there was no difference in mortality and extracorporeal membrane oxygenation (ECMO) use, irrespective of surgical timing. There were two randomized trials which compared early repair (less than 12 hours of age) with delayed repair (after 24 hours9 or after 96 hours8), and neither identified a statistically significant difference in mortality. Although surgical modifications may be partially responsible for the improved overall survival over the last 20 years, concomitant advances in ventilatory strategies have certainly played a major role in minimizing mortality. Even though the current routine in most centers includes nonemergent surgery, there is no clear evidence to support delayed versus immediate surgical repair.10
Pre-operative stabilization Optimal initial postnatal resuscitation and management is aimed toward minimizing the physiologic derangements associated with pulmonary hypoplasia and pulmonary hypertension. Following delivery (or postnatal diagnosis of CDH), prompt endotracheal intubation (without high-pressure bag ventilation), nasogastric tube placement, and arterial/venous catheter placement are important initial maneuvers for pulmonary and hemodynamic support.11 Oxygenation and acid-base status should be closely monitored. An infant is considered ready for operation once they are hemodynamically stable, have reached an acid-base status within the normal physiologic range, and are able to tolerate conventional ventilation, while maintaining adequate oxygenation.11,12 Clear, objective, universal criteria to define physiologic stabilization have not been accepted, therefore leaving each center to determine the methods and endpoints of preoperative stabilization. General guidelines include minimal ventilatory support, resolution of pulmonary hypertension, improvement in pulmonary compliance, and resolving pulmonary radiographic abnormalities.10,13 There are exceptions to these indications, such as patients requiring ECMO, and these are addressed below. Some infants stabilize quickly and can undergo repair within 48 hours of birth, whereas others may require weeks of medical management before operation. Irrespective of the preoperative delay, the key principle is that initial morbidity is the result of pulmonary hypoplasia and pulmonary hypertension; management requires a delicate balance of hemodynamic stabilization, permissive hypercapnea, and respiratory support while minimizing iatrogenic pulmonary injury.11 The
Seminars in Pediatric Surgery, Vol 16, No 2, May 2007 precise length or endpoint of stabilization, as discussed earlier, remains unclear.10
Extracorporeal membrane oxygenation In the late 1970s, the first reports of ECMO for infants with CDH14 provided a potential therapy for these children with severely hypoplastic lungs. Since that time, the strategy for ECMO has undergone continual refinement and critical examination. Approximately one-third of infants born with CDH will be treated with ECMO during their initial course of management.15,16 The previously accepted indications for initiation of ECMO include an Oxygenation Index (OI) ⬎40, PaCO2 consistently ⬎12, and an A-a gradient consistently ⬎600 mmHg.11,12,17 The most common indication for ECMO in the infant with CDH today is “failure to respond.” Most centers have established criteria that limit the allowable positive pressure on the ventilator. When the patient requires more than a set level of support, ECMO is utilized rather than escalating the amount of positive pressure ventilation. An OI ⬎40 is much less frequently used as an indication for ECMO in patients with CDH. In addition, the presence of an intracranial hemorrhage ⬎Grade I, gestational age ⬍34 weeks, significant additional congenital abnormalities, or lethal chromosomal abnormalities should preclude initiation of ECMO. Among infants where conventional medical therapy fails to maintain oxygenation or normal acid-base status, ECMO should be considered. Although ECMO was initially utilized postoperatively,18 the trend toward preoperative use, often extending through surgery, has coincided with the trend of preoperative stabilization.19 ECMO has become one of the management options for respiratory failure during preoperative stabilization. ECMO for pre-repair stabilization was popularized in the late 1980s, as the management paradigm shifted from emergent surgery. Early reports of stabilization and subsequent repair on ECMO highlighted the benefit of ECMO before delayed repair, particularly among high-risk infants.20,21 One group compared infants treated without ECMO to infants stabilized on ECMO before repair and found an improvement in overall survival from 43% to 67% (P ⬍ 0.05).21 In 2002, the CDH Study Group reported that 85% of infants requiring ECMO had support initiated pre-repair.22 Of patients placed on ECMO pre-repair, 54% underwent repair while on ECMO and 29% underwent repair after decannulation, leaving 16% that were never repaired. Infants that underwent repair on ECMO had a 50% mortality, whereas those that underwent repair after ECMO had a 17% mortality. The majority of patients requiring support were placed on ECMO in the first 24 hours of life. A large proportion of patients placed on ECMO preoperatively undergo repair while on ECMO.19 In 1998, the CDH Study Group reported that 19% of all CDH repairs
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were performed while on ECMO and 33% of patients placed on ECMO underwent repair on ECMO.13 As hemorrhage is a known complication among infants requiring ECMO,23 several centers have studied strategies to decrease bleeding and report minimal hemorrhagic complications.24,25 The use of aminocaproic acid (Amicar®), an inhibitor of fibrinolysis, was initially reported in 1990 in an attempt to limit intracranial hemorrhage (ICH).26 A pilot study showed that Amicar® decreased the incidence of ICH and other hemorrhagic complications, while inciting minimal thrombotic complications.27 A subsequent multicenter, prospective, randomized trial of 29 infants found that Amicar® was safe, but there was no difference in hemorrhagic complications, including ICH, between the treatment and placebo groups.28 Of note, CDH patients were excluded from this study. Downard and colleagues followed up their pilot study with a recent review of their use of Amicar® in high-risk patients over the last 10 years.15 They defined high-risk patients as those with an increased likelihood of hemorrhage secondary to preexisting or anticipated surgical procedure, severe hypoxia/acidosis, prematurity, prior ICH, or profound, uncorrectable coagulopathy. They compared patients receiving Amicar® at their institution with similar patients in an ECMO registry. Although they did not identify a statistically significant difference in mortality or ICH between the two groups, the rate of surgical site bleeding was significantly reduced in the Amicar® group (P ⫽ 0.005). It has become routine to use Amicar® when patients require surgical repair on ECMO if there are no contraindications.
Surgical approach and principles The traditional approach to repair of the diaphragmatic defect is via a subcostal incision on the ipsilateral side of the hernia. More than 90% of surgeons use this incision, whereas only 6% prefer the thoracic approach.13 After reduction of the abdominal viscera from the thorax and evisceration of the bowel to achieve adequate exposure, a true hernia sac (present only 10-20% of the time) should be identified and excised. Depending on the size of the defect, there are three general operative strategies. If the defect is small, it should be closed primarily with nonabsorbable suture. If the defect is relatively large, attempted primary closure may leave the patient with a flattened diaphragm and inferior pulmonary compliance. Alternatively, a prosthetic patch [such as polytetrafluoroethylene (PTFE), the most commonly used prosthetic material13] can be tailored to restore a more natural, tension-free diaphragm shape. Many types of patch closure, from muscle flaps to bioactive prosthetic materials, have been described (Table 1). The disadvantage with the use of a synthetic material is lack of material growth, leading to hernia recurrence in nearly 50% of patients.29 In an effort to prevent the recurrent hernia, specialized techniques have been developed and reported. Loff and colleagues described the use of a cone-shaped,
111 Table 1
Repair options for large defects13
Prosthetic materials: Polytetrafluoroethylene (PTFE) (Gore-Tex) Polypropylene (Marlex) Dacron Muscle flaps: Abdominal42 Latissimus dorsi43 Latissimus dorsi and serratus anterior32 Bioactive Materials: Surgisis44
double-fixed PTFE patch that reduced their recurrences (within the first year after repair) from 46% to 9%.30 The cone shape increased abdominal capacity and created a more physiologic diaphragm, and the double fixation improved the overall stability. Fuchs and associates developed an autologous tendon engineered from mesenchymal amniocytes in an ovine model.31 They found that when the cellular construct was used for diaphragmatic repair, the lambs experienced improved mechanical and functional outcomes when compared with an equivalent acellular bioprosthetic repair. Developments in cellular-based therapies hold promise in developing tissue that could grow with the patient. For very large defects (or agenesis of the diaphragm), the posterior rim of the diaphragm, as well as the medial component, may be absent. To handle this more challenging repair, the prosthetic patch should be secured to the abdominal wall or to the ribs. Securing the patch medially may be especially difficult. These patients, who require a large patch, will have a recurrence nearly 100% of the time, as the synthetic material does not grow with the child. The initial repair in these patients should be considered the first operation of a staged procedure. Case reports of the use of reverse latissimus dorsi and serratus anterior muscle flaps hold promise in these difficult cases, as the native tissue may offer the advantage of continued growth of the reconstructed diaphragm.32 If closure of the abdominal fascia is likely to increase intraabdominal pressure enough to exacerbate the respiratory compromise, the fascia should be left open. Infants who require ECMO before CDH repair are more likely to have abdominal wall closure problems secondary to loss of abdominal domain.33 Coverage may then be achieved via skin closure, creation of a Silo, or abdominoplasty.34 Schnitzer and colleagues advocated suturing a Vicryl mesh patch to the fascial edges before skin closure. They felt that this would serve as an additional protective barrier and help to clarify the dissection during the subsequent definitive closure.33 For infants repaired on ECMO, or infants likely to require postoperative ECMO, special considerations are warranted. Fibrin or thrombin sealants should be considered to reduce the chance of suture line hemorrhage. The use of Amicar®, as discussed above, may prevent hemorrhagic
112
Seminars in Pediatric Surgery, Vol 16, No 2, May 2007 lator support (PIP ⬍24), and no evidence of pulmonary hypertension. They found thoracoscopic primary repair to be safe, feasible, and comparable to open repair in their seven patients, although one patient developed a recurrence.
Recurrent diaphragmatic hernia
Figure 1 Operative positioning for the minimally invasive approach to a Morgagni hernia: Modified Fowler position. (Reprinted with permission.36)
complications. Very careful inspection of the operative field for hemostasis on completion of the case is paramount. Tube thoracostomy is infrequently indicated,35 but occasionally necessary for draining significant hemorrhage,11 uncontrolled air leak,11 chylothorax, pneumothorax, or a large pleural effusion. Tube thoracostomy is postulated to cause contra- and ipsilateral iatrogenic pulmonary injury via mediastinal shift after pleural suction and, therefore, has fallen out of favor unless necessary. Usually, the lungs will gradually displace fluid and air as they enlarge.
Changes in the medical and surgical management have improved survival and, consequently, have exposed previously uncommon additional morbidity. Recurrence of the diaphragmatic defect is one such complication. Prevention of recurrent herniation requires that the reconstructed diaphragm grow with the patient. This growth is dependent on cellular deposition, proliferation, and organization into tissue. Such tissue organization requires vascular supply. Current theory, given the location of the diaphragm, is that limited growth of the reconstructed diaphragm is secondary to lack of vessel formation and in-growth. The overall rate of recurrence in most published series ranges from 14% to 22%.21,38,39 It is impossible to compare or generalize the few studies given the retrospective designs, lack of standardization of defect severity, highly variable repair strategy, and inconsistent follow-up. There are several factors likely associated with increased risk of recurrence. Hajer and coworkers had a 14% incidence of recurrence and identified a right-sided defect, a large defect, a patch closure, and the use of ECMO as four factors that lead to a statistically significant increase in recurrence.38 Moss and coworkers examined patch durability and noted a 41% recurrence,29 nearly identical to the 42% recurrence with patch repairs that Hajer and coworkers
Minimally invasive surgery Advances in minimally invasive surgery (MIS) have led to both thoracoscopic and laparoscopic repairs of CDH. Arca and coworkers described the technical development of their minimally invasive approach to 15 children.36 They found laparoscopy to be a better approach to Morgagni defects (Figure 1) and thoracoscopy a better approach to Bochdalek defects (Figure 2). They concluded that MIS was ideal for Morgagni defects, but that Bochdalek repair (via thoracoscopy) should be approached cautiously based on their high failure rate (14%), prohibitive increases in PCO2, and acidemia.36 Subsequently, Yang and colleagues formulated preoperative patient selection criteria to maximize successful thoracoscopic diaphragm repair.37 Preoperative requirements included an intraabdominal stomach, minimal venti-
Figure 2 Minimally invasive approach to Bochdalek defects. (A) Operative positioning for a Bochdalek hernia. The infant should be placed left side up about 45° from the horizontal with a slight reverse Trendelenburg position. (B) Port placement for thoracoscopic Bochdalek hernia repair. (Reprinted with permission.36)
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reported. Because most very large defects require patch repair, it is difficult to isolate the critical factor. A missed hernia sac is sometimes identified in patients that recur,38,39 causing it to be associated with increased risk for recurrence as well. Hajer and coworkers reported an average latency of 4 months (0.2-6.9 months),38 and Slatzman and colleagues reported an average of 8 months latency (2-16 months)40 between surgery and recurrence. Late recurrences are uncommon. Recurrent hernias can present with respiratory (dyspnea) or gastrointestinal symptoms, and can usually be confirmed via chest x-ray. Moss and colleagues identified second recurrences or re-recurrences in 25% of their patients that experienced recurrence.29 There is limited evidence evaluating the optimal timing for repair after recurrence. Some surgeons proceed with prompt repair, minimizing the risk of incarceration. However, early repair in a newborn could be high risk and, therefore, the surgeon may opt for delay with close follow up, particularly if the patient is without serious symptoms secondary to the re-herniation. If the risks of the operation outweigh the benefits of immediate repair, close monitoring, including routine physical examination and chest radiography, is paramount. Some surgeons choose to approach the re-repair via the chest, especially if the primary repair was approached through the abdomen. No study has compared the thoracic versus the abdominal approach. On rare occasion, exposure from the chest and the abdomen is required. As with the primary procedure, the guiding principle of re-repair is to reduce the abdominal contents and close the defect. This may be accomplished in a primary fashion or frequently will require additional patch placement. Saltzman reported five successful repairs using a novel hernia plug approach, where a polypropylene mesh plug was placed in the defect via an anterolateral thoracotomy.40 Bianchi reported three successful repairs using a reverse latissimus dorsi muscle flap.41 As a broad, thin, well-vascularized sheet of muscle, the latissimus dorsi was found to be well suited to replace the entire hemidiaphragm. Although they reported its use for recurrence, they recommended considering its use at the primary operation if insufficient tissue was available.
Conclusion The management of CDH has seen steady progress over the last 20 years. Today, overall survival has reached 80% in live-born infants as a direct result of changes in medical and surgical management. Preoperative physiologic stabilization and subsequent elective repair have become the cornerstones of management. In many centers, ECMO is a key component of stabilization. Although elective repair has become routine, optimal timing of operation remains unclear. The role of minimally invasive surgery is undefined,
113 but instrumentation and techniques continue to improve. Although recurrent herniation remains high, ongoing research is focused on the development of new materials and new techniques to allow the diaphragm to grow with the patient. With burgeoning alternative medical and surgical strategies, novel clinical and basic science research, and multi-institutional cooperation, management of these patients is certain to continue to evolve.
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114 21. West KW, Bengston K, Rescorla FJ, et al. Delayed surgical repair and ECMO improves survival in congenital diaphragmatic hernia. Ann Surg 1992;216:454-60. 22. Lally KP, CDH Study Group. The use of ECMO for stabilization of infants with congenital diaphragmatic hernia, 2002. American Academy of Pediatrics, Surgical Section. 2002 (Abstract) 23. Vazquez WD, Cheu HW. Hemorrhagic complications and repair of congenital diaphragmatic hernias: does timing of the repair make a difference? Data from the Extracorporeal Life Support Organization. J Pediatr Surg 1994;29:1002-5. 24. Austin MT, Lovvorn HN 3rd, Feurer ID, et al. Congenital diaphragmatic hernia repair on extracorporeal life support: a decade of lessons learned. Am Surg 2004;70:389-95. 25. Wilson JM, Bower LK, Lund DP. Evolution of the technique of congenital diaphragmatic hernia repair on ECMO. J Pediatr Surg 1994;29:1109-12. 26. Ackerman N, Lyon J, Ratner I, et al. A proposal for a multicenter trial of 6-amino-hexanoic acid (AMICAR) for the prevention of bleeding of infants on ECMO. Presented at the 2nd Annual ELSO meeting, Ann Arbor, MI, 1990. 27. Wilson JM, Bower LK, Fackler JC, et al. Aminocaproic acid decreases the incidence of intracranial hemorrhage and other hemorrhagic complications of ECMO. J Pediatr Surg 1993;28:536-41. 28. Horwitz JR, Cofer BR, Warner BW, et al. A multicenter trial of 6-Aminocaproic Acid (Amicar) in the prevention of bleeding in infants on ECMO. J Pediatr Surg 1998;33:1610-3. 29. Moss RL, Chen CM, Harrison MR. Prosthetic patch durability in congenital diaphragmatic hernia: a long-term follow-up study. J Pediatr Surg 2001;36:152-4. 30. Loff S, Wirth H, Jester I, et al. Implantation of a cone-shaped doublefixed patch increases abdominal space and prevents recurrence of large defects in congenital diaphragmatic hernia. J Pediatr Surg 2005;40: 1701-5. 31. Fuchs JR, Kaviani A, Oh JT, et al. Diaphragmatic reconstruction with autologous tendon engineered from mesenchymal amniocytes. J Pediatr Surg 2004;39:834-838.
Seminars in Pediatric Surgery, Vol 16, No 2, May 2007 32. Samarakkody U, Klaassen M, Nye B. Reconstruction of congenital agenesis of the hemidiaphragm by combined reverse latissimus dorsi and serratus anterior muscle flaps. J Pediatr Surg 2001;36:1637-40. 33. Schitzer JJ, Kikiros CS, Short BL, et al. Experience with abdominal wall closure for patients with congenital diaphragmatic hernia repaired on ECMO. J Pediatr Surg 1995;30:19-22. 34. Conforti AF, Losty PD. Perinatal management of congenital diaphragmatic hernia. Early Hum Dev 2006;82:283-7. 35. Wung JT, Sahni R, Moffitt ST, et al. Congenital diaphragmatic hernia: survival treated with very delayed surgery, spontaneous respiration, and no chest tube. J Pediatr Surg 1995;30:406-9. 36. Arca MJ, Barnhart DC, Lelli JL Jr, et al. Early experience with minimally invasive repair of congenital diaphragmatic hernias: results and lessons learned. J Pediatr Surg 2003;38:1563-8. 37. Yang EY, Allmendinger N, Johnson SM, et al. Neonatal thoracoscopic repair of congenital diaphragmatic hernia: selection criteria for successful outcome. J Pediatr Surg 2005;40:1369-75. 38. Hajer GF, vd Staak FH, de Haan AF, et al. Recurrent congenital diaphragmatic hernia; Which factors are involved? Eur J Pediatr Surg 1998;8:329-33. 39. Rowe DH, Stolar CJ. Recurrent diaphragmatic hernia. Semin Pediatr Surg 2003;12:107-9. 40. Saltzman DA, Ennis JS, Mehall JR, et al. Recurrent congenital diaphragmatic hernia: a novel repair. J Pediatr Surg 2001;36:1768-9. 41. Bianchi A, Doig CM, Cohen SJ. The reverse latissimus dorsi flap for congenital diaphragmatic hernia repair. J Pediatr Surg 1983;18: 560-3. 42. Joshi SB, Sen S, Chacko J, et al. Abdominal muscle flap repair for large defects of the diaphragm. Pediatr Surg Int 2005;21:677-80. 43. Sydorak RM, Hoffman W, Lee H, et al. Reversed latissimus dorsi muscle flap for repair of recurrent congenital diaphragmatic hernia. J Pediatr Surg 2003;38:296-300. 44. Grethel EJ, Cortes RA, Wagner AJ, et al. Prosthetic patches for congenital diaphragmatic hernia repair: Surgisis vs Gore-Tex. J Pediatr Surg 2006;41:29-33.