Necrotizing Enterocolitis C. Stefan Kénel - Pierre, MD SUNY Downstate Department of Surgery May 2012
Transcript
Necrotizing Enterocolitis
C. Stefan Kénel - Pierre, MD
SUNY Downstate Department of Surgery
May 2012
Presenter
Presentation Notes
Good morning. Today I will be discussing Necrotizing Enterocolitis. For those who don’t know me, my name is Stefan Kénel-Pierre.
Case Presentation • Twin female ex-27 weeker, delivered to a
22 year old primigravida via caesarian section for severe pre-eclampsia
• Birth weight 1095 grams • Apgar score 8/9 • Intubated and treated with surfactant.
Presenter
Presentation Notes
The patient is a twin female, former 27 week gestation delivered to a 22 year old lady, primigravida via caesarian section for severe pre-eclampsia. The patient weighed 1095 grams at birth with Apgar scores of 8 and 9 and 1 and 5 minutes respectively with points substracted for acrocyanosis and poor respirations. At this point the patient was intubated, taken to the neonatal ICU and started on surfactant treatment.
History of Present Illness • Feeds started on DOL #2, held DOL 4-6
• DOL 23-24: second episode of hypoxia and bradycardia, increased residual feeds
• Pediatric surgery called for evaluation.
Presenter
Presentation Notes
Orogastric tube feeds were started on day of life #2 and held from days 4 to 6 after the patient received indomethacin for large patent ductus arteriosus. On day of life 15, the patient had an episode of desaturation and bradycardia for which she was placed on broad spectrum antibiotics for suspected neonatal sepsis. On day of life 23-24, the patient experienced a second episode of hypoxia and bradycardia accompanied by increased residual feeds. Pediatric surgery was called for evaluation after the patient had a bloody bowel movement and was found to be increasingly irritable with a distended abdomen. At the time of initial evaluation, the patient was on Vancomycin, Gentamicin, meropenem., caffeine and dopamine infusion.
discoloration in LLQ, distended, firm. +tenderness to palpation. No palpable inguinal hernias
Presenter
Presentation Notes
Physical examination was notable for a heart rate of 200 and an edematous, ecchymotic tender abdomen.
Laboratory Values
• ABG 7.01/71.7/52/18.1/-13/66%
• CBC 8.4>9.5/30.8<167 Bands 14% @ 22:00
• CBC 15.5>11.2/34<65 Bands 18% @ 04:00
• BMP 132/8.7/103/22/29/1<81
Presenter
Presentation Notes
Laboratory findings were significant for severe mixed acidosis, progressive thrombocytopenia, and hyperkalemia, although the latter was from a hemolyzed sample. A portable X-ray was obtained.
Radiology
Presenter
Presentation Notes
Here we find Rigler’s sign (air on both sides of bowel wall), the falciform ligament and the beginning of air in the portal venous system, all of which point to pneumoperitoneum. Based on our clinical impression, the patient had severe necrotizing enterocolitis, and warranted exploration in the operating room for further management.
Intraoperative Findings
Presenter
Presentation Notes
Intraoperatively we encountered diffuse necrotizing enterocolitis, involving almost the entire small bowel, from the ligament of Treitz to the ileocecal valve. Given these findings, the patient’s abdomen was closed with further intervention deemed futile by the operating surgeon.
Postoperative Course • Case aborted; no further surgery planned
• NICU pursued aggressive management
• Patient was transferred to UHB-LICH
• Second look one week later
• Massive small bowel resection
• Multiple returns to the OR for free air
Presenter
Presentation Notes
Despite this, the Neonatal ICU continued aggressive management of the patient and sought a second opinion. The patient was transferred to Long Island College Hospital where she remains. A second look surgery was performed approximately 1 week following the initial operation. The patient underwent a massive small bowel resection, duodenoileostomy with approximately 1.5 cm of ileum left. She has sinced returned to the operating room more than three times for pneumoperitoneum with revision of anastamoses. Are there any questions about the case?
Outline • Background • Clinical Presentation • Pathophysiology • Staging • Treatment Options • Complications of NEC • Controversy
Presenter
Presentation Notes
As the case suggests, today I will be speaking about necrotizing enterocolitis. We will begin with some background information, followed by a review of the clinical presentation and pathophysiology. Staging and treatment options will then be covered. Complications of NEC will be subsequently addressed and finally we will talk about controversies surrounding the disease.
Background • Most frequent neonatal surgical emergency
• Over 25,000 cases reported annually
• 1-3 in 1000 live births
• 30 in 1000 low birth weight infants
• 50% infants with NEC weigh <1,500 g
• Mortality 10-50%
Presenter
Presentation Notes
Necrotizing enterocolitis is the most common gastrointestinal emergency in the neonatal period. Although there have been several contributing factors such as ischemia, bacteria, tube feeds and cytokines discussed in the literature, the single most important risk factor is prematurity. In the United States, there are over 25,000 cases reported annually, this accounts for approximately 1 to 3 in 1000 live births, but close to 30 in 1000 in low birth weight infants. With new innovations in neonatal care, patients are being maintained at increasingly shorter gestation times and subsequently much smaller sizes. Approximately 50% of infants with NEC weigh less than 1500 grams. Despite the many technological advances, and perhaps as their direct result, mortality rates for NEC have not improved, and in some studies, have worsened. Generally
As mentioned earlier prematurity and enteral feeding (particularly hyperosmolar feeding) are risk factors for the development of necrotizing enterocolitis. In addition, any ischemia-inducing factors, such as hypotension, maternal cocaine use with vasoconstriction and the use of umbilical catheters are also risk factors. Finally patients with patent ductus arteriosus leading to pulmonary hypertension and congestive heart failure are also at risk for the development of NEC.
Clinical Signs • Abdominal Distention
• Feeding intolerance
• Bilious Emesis
• Occult/Gross hematochezia
Presenter
Presentation Notes
Although clinical presentation can vary considerably from case to case, patients most often present with increased residual feeds or feeding intolerance. This can be followed by emesis, abdominal distention, however these are very general symptoms. Bloody stools, on the other hand, are a more ominous sign, pointing towards a likely diagnosis of necrotizing enterocolitis. Neonates will often have periods of apnea and bradycardia during . Thrombocytopenia is secondary to decreased megakaryocytopoeisis from hypoxia
Radiologic Signs
Presenter
Presentation Notes
Plain films of the abdomen may demonstrate frank free air, however this is not always observed. More subtle findings, such as Rigler’s sign (where air can be seen on both sides of the bowel wall, as well as air around the falciform ligament are other radiologic findings consistent with pneumoperitoneum.
Pathophysiology • Pathophysiology is poorly understood
• Three hypotheses:
– Hypoxia and mucosal Injury
– Intestinal Immaturity
– Presence of Bacteria
Presenter
Presentation Notes
There has been much debate on the origins of NEC. To this day, the pathophysiology remains cloudy, however the great majority of studies have focused on three different, but related hypotheses: hypoxia and mucosal injury, intestinal immaturity, and the presence of bacteria.
– Present in diving mammals and birds – Hypoxia bradycardia & shunting blood flow – Brain & heart remain perfused in shock state
• Theory recently questioned • Hypoxia induces vascular regulators (NO)
Presenter
Presentation Notes
Initially, the work of Lloyd and Scholander drew similarities between diving mammals and neonates, referring to the reflex that allowed whales, dolphins, etc to stay long periods of time submerged in water. The thought was that during periods of hypoxia, there is reflex bradycardia and redistribution of blood flow away from the splanchnic circulation toward the heart and brain to maintain perfusion. Given the relatively low blood volume of neonates, such shunting would result in mesenteric ischemia and eventual necrosis. The validity of the statement has been recently called into question in favor of other hypotheses that we will discuss later. Nonetheless, it should be noted that hypoxia induces vascular regulators such as nitric oxide which can lead to vaso-dilatation, increasing blood flow to the intestines. When uncontrolled however, this may lead to increased permeability and subsequent cellular injury.
Intestinal Immaturity • Gastric acid secretion limited in preterm • Excessive inflammatory reponse IL-8 leading to necrosis
• Preterm enterocytes are unprepared
Presence of Bacteria • Fecal & gastric flora distinct in prematurity • Bell postulated difference was due to:
– Prolonged Hospital Stay – Mechanical Ventilation – Indwelling catheters – Different feeding regimes – Use of antibiotics
• NEC “outbreaks”
Presenter
Presentation Notes
The presence of bacteria in the gut has been suggested as being central to the development of NEC. This hypothesis is further supported, not only that the NEC outbreaks often observed in neonatal ICUs, but also by the significant difference in gastric and fecal flora in the premature infant.
Staging
• Bell Criteria
• Vermont Oxford Network Classification
Presenter
Presentation Notes
Although there have been many grading systems for NEC, which in itself points to the lack of universally reliable criteria, the best known is the Bell criteria developed in 1978. We will discuss this in more detail later. Another classification system published in the Vermont Oxford Network Manual of Operations describes clinical and radiologic findings such as bilious gastric aspirate or emesis, abdominal distention, and occult gross blood in the stool, imaging findings include pneumatosis intestinalis, hepatobiliary gas, and pneumoperitoneum. Both systems have shortcomings however as severe NEC can present without portal venous gas or pneumoperitoneum on imaging. Thus, progression of disease can be missed and we may fail to intervene in a timely fashion.
Staging • Stage I (suspected)
– Systemic manifestations • Apnea, bradycardia, temperature instability, lethargy
– Incision in right lower quadrant – 1/3 improve; 1/3 die – 1/3 require further operative intervention
Presenter
Presentation Notes
Surgical intervention is dependent on stage. If a focal segment of ischemia is encountered, the operative options differ from a patient with multiple segments or NEC totalis. With regards to delayed revision, norm is to wait 6 weeks, however this has recently been questioned as demonstrated by a group from Netherlands (Struijs et al 4/2012 J Ped Surg) Peritoneal drainage has also been considered, and studies demonstrate some benefit in low birth weight infants. We will address this further shortly.
Necrotizing Enterocolitis can result in bleeding, infection, stricture formation. In neonates with surgical NEC, one should be wary of anastamotic leaks, enterocutaneous fistula, stoma related complications and other complications.
Strictures • Frequently occur in patients with NEC
• Radiology studies prior to ostomy closure
• Most commonly found in
1. Left colon
2. Right Colon
3. Terminal Ileum
Presenter
Presentation Notes
Intestinal stricture formation following NEC, whether managed operatively or nonoperatively, is common, occurring in roughly 20% of affected patients. This consequence usually results from a normal host inflammatory response to transmural intestinal injury. The degree of fibrosis and stricture formation are related to the severity and extent of disease. Strictures can develop anywhere, with a higher rate in the left colon. Routine contrast enema 4 to 6 weeks after clinical resolution of NEC treated operatively or nonoperatively has been advocated in some institutions. This should be stressed in patient with ostomies prior to reversal. Symptomatic strictures generally require segmental resection with anastomosis, although fluoroscopically guided balloon catheter dilatation has been reported.
Total Parenteral Nutrition • Patients rely upon TPN for caloric intake • Long term TPN can lead to
– Cholestasis – Cirrhosis – Sepsis – Death
• D. bilirubinemia > 4 for 6m: 80% mortality
Short Bowel Syndrome
• NEC: #1 cause of neonatal SBS
• Less than 40% of normal length
• As much as 50% can be resected
• Treatment: TPN, H2 blocker, anti-diarrheal
Presenter
Presentation Notes
For those patients with extensive NEC, as in the case presented earlier, a significant number will develop short bowel syndrome. Technically this term is employed to describe the condition resulting from resection of functioning gut to a length below that necessary for adequate absorption of nutrients, we can estimate this at less than 40% of normal length. This can vary widely based upon anatomical location of resection (and more specifically to the presence of the ileocecal valve). Resection of jejunum is far better tolerated than ileal resection, for example, as the ileum is able to adapt more readily. Initial treatment for short bowel syndrome includes TPN, H2 blockade for gastric acid hypersecretion, and anti-motility agents, such as lomotil/loperamide to decrease the fluid losses from malabsorptive diarrhea.
Surgical Options for SBS • Bianchi Procedure
• Interposition of antiperistaltic segment
• STEP Procedure
• Small Bowel Transplantation
Presenter
Presentation Notes
With failure of medical treatment, surgical options were became part of the management of short bowel syndrome. From the use of antiperistaltic segments to slow transit to small bowel transplantation, there are indeed multiple operative strategies one could employ. Among the most discussed are the Bianchi and STEP procedures.
Bianchi Procedure
Presenter
Presentation Notes
The Bianchi procedure as originally described, is an intestinal lengthening procedure whereby the mesentery is separated in two systems and the small intestine split into two parallel segments. The diameter is halfed, however the length is increased twofold. Risks of bowel necrosis from infarcted mesentary and anastamotic leaks are real however.
STEP Procedure
Presenter
Presentation Notes
The STEP or serial transverse enteroplasty procedure, first described in 2003, is another noteworthy procedure. dilated small intestine is serially stapled in a transverse fashion to create a narrower lumen and longer intestinal length. In a report of early experience with 16 patients, the STEP procedure improved enteral feeding tolerance, resulting in significant catch-up growth, and was not associated with increased mortality.
Small Bowel Transplant • Rates have improved with tacrolimus
– Infants c NEC hospitalized ~ 20-60 days more – Infants with short gut syndrome ~ $1.5 million
Presenter
Presentation Notes
The excessive inflammatory response initiated in the gut is extended systemically, thereby placing the infants at increased risk for pulmonary and neurodevelopmental delays. In fact, an infant recovering from NEC may have nearly a 25% chance of microcephaly and other severely disabiling neurologic sequelae. And although as physicians we may not like to think about the financial burden of a particular case on society, the length of stay for affected patients is significant. In one study, patients with NEC reportedly stayed an addition 20 days in house and closer to 60 days in those with surgical NEC. Even more impressive is the total mean cost of care in those with short gut syndrome nearly 1.5 million dollars over a 5 year period.
Probiotics • Meta-analyses suggest decreased NEC • Poorly powered, outside US, no RCTs • Exogenous probiotics can cause sepsis
– Study in adults showed 3x risk of mortality • These findings preclude recommendation
Prophylactic Antibiotics • Bacteria have role in development of NEC • Prophylactic antibiotics leads to resistance
Laparotomy vs Drainage • Drainage first described in 1977 by Ein
• Selected population: too ill for laparotomy
• Meta-analysis: 55% excess mortality in PD
• Sub - 1500g infants NEJM article Moss ’06
• Peritoneal drainage with delayed surgery
Summary • NEC is most frequent surgical emergency • Due to bowel immaturity and inflammation • Surgical intervention dependent on case • SBS and subsequent SB transplantation • No indication for probiotics • Drainage effective in highly selected group
References • Gilchrist, B et al. Necrotizing Enterocolitis. 2000 • Caty, MG et al. Complications of Pediatric Surgery.
2009 • Mulholland et al. Greenfield’s Surgery: Scientific
Principles & Practice 5th Ed. 2011 • Arensman et al. Pediatric Surgery 2nd Ed. 2009 • Townsend et al. Sabiston Textbook of Surgery: The
Biological Basis of Modern Surgical Practice. 2012 • Neu, J et al. Necrotizing Enterocolitis. NEJM 2011:364
