55: Gastrointestinal Bleeding from the Upper Tract

Vomiting of bright red blood or active bleeding from the nasogastric (NG) tube is seen. Upper gastrointestinal (GI) bleeding is bleeding that occurs proximal to the ligament of Treitz in the distal duodenum (esophagus, stomach, or duodenum). The majority of GI bleeds in neonates are benign, self-limiting, and require minimal workup and treatment, but it is important to detect the cases that have significant underlying pathology.

1. What are the vital signs? If the blood pressure is dropping and there is active bleeding, urgent crystalloid volume replacement is necessary.

2. What is the hematocrit? A spun or STAT hematocrit should be done as soon as possible. The result is used as a baseline value and to determine whether blood replacement should be performed immediately. With any acute episode of bleeding, the hematocrit may not reflect the blood loss for several hours.

3. Is blood available in the blood bank should transfusion be necessary? Verify that the infant has been typed and cross-matched so that blood will be quickly available if necessary.

4. Is there bleeding from other sites? Bleeding from other sites suggests disseminated intravascular coagulation (DIC) or other coagulopathy. If bleeding is coming only from the NG tube, disorders such as stress ulcer, nasogastric trauma, and swallowing of maternal blood are likely causes to consider in the differential diagnosis.

5. How old is the infant? During the first day of life, vomiting of bright red blood or the presence of bright red blood in the NG tube is frequently secondary to swallowing of maternal blood during delivery. Infants with this problem are clinically stable with normal vital signs.

6. What medications are being given? Certain medications are associated with an increased incidence of GI bleeding. The most common of these medications are indomethacin (Indocin), tolazoline (Priscoline), nonsteroidal anti-inflammatory drugs (NSAIDs), theophylline (rare), heparin, and corticosteroids. Some maternal medications can cross the placenta (aspirin, cephalothin, and phenobarbital) and cause coagulation disorders in the infant. Thiazides in pregnancy can be associated with neonatal thrombocytopenia.

7. Was vitamin K given at birth? Failure to give vitamin K at birth may result in a bleeding disorder, usually at 3–4 days of life.

8. Does the infant have a syndrome or condition that is associated with gastrointestinal bleeding? Down syndrome: Meckel diverticulum, Hirschsprung disease, pyloric stenosis. Turner syndrome: venous ectasia, inflammatory bowel disease. Klippel Trenaunay syndrome and blue rubber bleb nevus syndrome (BRBNS): vascular malformations. Osler Weber Rendu syndrome (hereditary hemorrhagic telangiectasia): epistaxis and vascular malformations, acute and chronic digestive tract bleeding. Epidermolysis bullosa: anal fissures, esophageal lesions, and strictures of the colon. Ehlers Danlos and pseudoxanthoma elasticum: fragile blood vessel wall structure. Hermansky-Pudlak syndrome: platelet dysfunction, inflammatory bowel disease. Glycogen storage disease type 1b: inflammatory bowel disease. Zellweger cerebrohepatorenal syndrome: GI bleeding.

9. Is there a history of melena? Melena signifies significant upper gastrointestinal bleeding or possibly swallowed maternal blood (see also Chapter 49).

1. Benign conditions that are not a true gastrointestinal bleed. Swallowing of maternal blood accounts for ∽10% of cases. Typically, blood is swallowed during cesarean delivery, but can occur with a vaginal birth as well. Swallowed blood irritates the stomach and can cause vomiting. Swallowing of blood from a cracked nipple or fissure during breast-feeding can also cause it. Swallowing of amniotic fluid with an antepartum hemorrhage bleeding into the amniotic fluid normally presents with melena stools but can present with upper GI bleeding.

2. True gastrointestinal bleed

   1. Idiopathic. More than 50% of cases have no clear diagnosis and usually resolve within several days.

   2. Stress-induced gastric bleeding/ulcers. These can be caused by an increase in gastric acid secretion and laxity of gastric sphincters in infants. Prematurity, neonatal distress, and mechanical ventilation are associated with stress gastritis. Maternal stress in the third trimester with increased maternal gastrin may also play a part. Upper gastrointestinal bleeding in healthy full-term infants is often associated with clinically relevant mucosal lesions of the upper GI tract.

      1. Esophagus. Esophagitis (hemorrhage or ulcerative), Mallory Weiss tear.

      2. Gastric. Gastritis, ulcer.

      3. Duodenum. Duodenitis, duodenal mucosal lesions, ulcer, vascular malformation; single stress ulcers are more common in duodenum than in stomach in a neonate.

      4. Gastroesophageal lesions. Infants tend to have gastric and esophageal lesions together.

   3. Trauma. Infants can swallow their own blood from trauma.

      1. Nasogastric trauma. Forceful insertion or too large a tube can cause trauma. Frequent aspiration to identify gastric residuals can cause trauma. The bleeding from this is usually minimal.

      2. Endotracheal tube insertion.

      3. Vigorous suctioning.

      4. Traumatic esophagitis. This has been reported in newborns possibly from pharyngeal, esophageal, or gastric suction at birth.

   4. Coagulopathy

      1. Hemorrhagic disease of the newborn (vitamin K–dependent coagulation factors deficiency) and DIC. Account for ∽20% of cases. This is rare due to vitamin K prophylaxis. Mothers who are on certain medications that interfere with vitamin K metabolism (eg, oral anticoagulant, isoniazid, rifampin, anticonvulsants) are at risk for hemorrhagic disease of the newborn.

      2. Congenital coagulopathies. Most commonly factor VIII deficiency (hemophilia A) and factor IX deficiency (hemophilia B) can cause GI bleeding from the upper tract.

      3. DIC. This can occur after infection, sepsis, shock, liver failure, and severe fetal asphyxia.

      4. Liver disease/failure in the newborn. Metabolic disorders that cause liver failure have associated coagulopathies that can present with GI bleeds. Ischemic injury to the liver can also present with GI bleeding. Portal vein thrombosis can cause bleeding.

   5. Allergic colitis is caused by allergy to cow's milk or soy after it has been introduced. Can present with upper GI or rectal bleeding. Rectal bleeding is a more common presentation.

   6. Sepsis can cause GI bleeding in a newborn.

   7. Necrotizing enterocolitis (NEC) is a rare cause of upper GI tract bleeding that indicates extensive disease.

   8. Medications (drug-induced bleeding). Indomethacin, corticosteroids, tolazoline, heparin, NSAIDs, sulindac, and other drugs may cause upper GI tract bleeding. Theophylline is a rare cause. High-dose dexamethasone is associated with stress and perforated ulcers and hemorrhage in the newborn. Maternal use of aspirin, cephalothin, and phenobarbital can cause coagulation abnormalities in neonates. Prenatal use of cocaine can predispose to GI bleeds.

   9. Congenital GI defects such as gastric volvulus, malrotation with volvulus, Hirschsprung disease with enterocolitis, intussusception, gastric/intestinal duplication, duplication cyst, and Meckel diverticulitis.

   10. Vascular anomalies such as arteriovenous malformations, extensive telangiectasias, gastrointestinal hemangiomas, etc with or without a related syndrome can present with GI hemorrhage.

   11. Pyloric stenosis presents at the third to fourth weeks of life with nonbilious projectile vomiting (occasionally bloody).

   12. Rare causes include gastric teratoma/gastric tumors, gastric Dieulafoy lesion, infection with Serratia marcescens, arteriovenous malformations, complication from intrapulmonary percussive ventilation (IPV) therapy, telangiectasia involving the entire GI tract, pyloroduodenal intestinal duplication, and heterotopic pancreatic tissue in the stomach.

1. Physical examination should focus attention on other possible bleeding sites. Note bowel sounds, abdominal distension and if there is any abdominal wall erythema.

2. Laboratory studies

   1. Initial tests

      1. Apt test. Should be performed if swallowed maternal blood is a possible cause. This test differentiates maternal from fetal blood. The test relies on the fact that hemoglobin F is not hydrolyzed by a strong base, whereas maternal hemoglobin A hydrolyzes to a yellow brown. However, a negative test does not completely rule out swallowed maternal blood.

      2. Hematocrit. Should be checked as a baseline and serially to gauge the extent of blood loss.

      3. Complete blood count (CBC) with differential. A change in the white blood cell (WBC) count may indicate infection. Thrombocytopenia is associated with NEC and sepsis.

      4. Coagulation studies (platelet count, prothrombin time [PT], partial thromboplastin time [PTT], fibrinogen, and international normalized ratio [INR]). To rule out DIC and other coagulopathies. An elevated PT and prolonged PTT may indicate a coagulopathy.

      5. Biochemistry panel. An elevated BUN (blood urea nitrogen) can be seen in a massive GI bleed.

   2. Additional tests

      1. Liver function. If cholestasis is a concern, total and direct bilirubin and liver function tests should be done.

      2. Serum pepsinogen level. Elevated levels can indicate severe atrophic gastritis and gastric atrophy and can be elevated in infants with gastric and duodenal lesions.

3. Imaging and other studies

   1. Immediate tests

      1. Abdominal radiograph. Assesses the bowel gas pattern and rules out NEC. The film also shows the position of the NG tube and indicates a possible surgical problem. It can help identify a pneumoperitoneum, small bowel dilatation, and pneumatosis.

   2. Additional tests

      1. Upper GI series. A barium contrast study can be done for nonemergent bleeding. It can evaluate for upper GI bleed or midgut volvulus. Not recommended when acute bleeding is occurring.

      2. Fiber optic/flexible upper GI endoscopy (esophagogastroduodenoscopy [EGD]). Should be considered and can reveal the source of bleeding in 90% of patients with upper GI bleeding. It is safe and should be considered in bleeding that is persistent or recurrent, or in cases of severe hemorrhage requiring blood transfusion. It can examine the esophagus, stomach, and duodenum, and biopsies can be taken. In one study the most common lesion identified by endoscopy was gastroesophagitis (unique to neonates).

      3. Ultrasound. If pyloric stenosis is suspected, ultrasound of the abdomen should be done. It can also show portal hypertension.

      4. Hepatobiliary scan. To rule out biliary atresia and neonatal hepatitis.

4. Nasogastric lavage can identify blood within the stomach and can help determine if the bleeding is ongoing. The presence of fresh blood in the stomach is diagnostic of upper GI bleeding, including duodenal hemorrhages. If the lavage is negative, then there is no active UGI bleeding.

1. General measures. The most important goal is to stop the bleeding in every case except those involving infants who have swallowed maternal blood. Infants with this problem are usually only a few hours old, are not sick, and usually have a positive Apt test result. Once stomach aspiration is performed, no more blood is obtained. Pediatric gastroenterologist/pediatric surgery consultation is recommended for significant upper GI bleeding.

2. Significant upper GI bleed with signs of decreased vascular volume.

   1. Volume replacement. If the blood pressure is low or dropping, crystalloid (usually normal saline) can be given immediately. Blood replacement may be indicated, depending on the amount of blood loss and the result of hematocrit values obtained from the laboratory. Fresh frozen plasma (FFP) and platelet transfusions may be necessary.

   2. Supplemental oxygen therapy should be started if needed.

   3. Stop the acute episode of GI bleeding

      1. Gastric lavage (with tepid water, 1/2 normal saline [NS], or NS 5 mL/kg) by NG tube until the bleeding has subsided. (Note: There is controversy about which fluid to use. Some believe that hyponatremia may occur if water is used and hypernatremia if NS is used. Follow your institution's guidelines.) Never use cold-water lavages (lowers the infant's core temperature too rapidly). Gastric lavage is controversial and there is no definitive evidence to support that it controls hemorrhage. This should not be done beyond 10 minutes if the NG fluid does not clear.

      2. Epinephrine lavage (1:10,000 solution), 0.1 mL diluted in 10 mL of sterile water, can be used if tepid water lavages do not stop the bleeding (controversial).

      3. Endoscopic hemostatic techniques may be necessary in massive bleeds and includes electrocoagulation, laser photocoagulation, heater probe thermocoagulation, and the injection of sclerosing agents and epinephrine.

3. Upper GI bleed that is benign and minimal can be observed if there is no evidence of active bleeding and a normal hematocrit. Antisecretory medications (H₂ blockers and proton pump inhibitors) can be used if indicated (see next section).

4. Disease-specific measures

   1. Idiopathic. When no cause is determined, the bleeding usually subsides and no other treatment is necessary.

   2. Swallowing of maternal blood. Observation only.

   3. Stress ulcer/mucosal lesions. Commonly diagnosed after an episode of GI bleeding by endoscopy. This disorder is difficult to confirm using radiologic studies; thus, they are not often requested. Remission usually occurs; recurrence is rare. Rarely surgery is necessary.

      1. Antacids may be used (eg, Maalox, 0.5–1 mL/kg or 0.25 mL/kg, 6 times per day, placed in the NG tube until bleeding has subsided). This is controversial because it may cause concretions in the GI tract. Antacids may increase the risk of infection and feeding intolerance in infants receiving gavage feedings. Calcium- and aluminum-containing antacids cause diarrhea; magnesium-containing antacids cause constipation.

      2. H₂ blockers inhibit gastric acid production in neonates and are usually recommended. Start ranitidine or famotidine (see Chapter 148 for dosing). Ranitidine and famotidine are preferred because they have fewer side effects. Follow your institution's guidelines. Cimetidine is rarely used because of adverse effects and clinically significant drug interactions. H₂-blocker therapy is associated with higher rates of NEC in very low birthweight infants and infections.

      3. Proton pump inhibitors are used if H₂ blockers do not work and are superior to H₂ blockers in the treatment of peptic ulcer after endoscopy. These include esomeprazole (Nexium), omeprazole (Prilosec), lansoprazole (Prevacid), rabeprazole (AcipHex), and pantoprazole (Protonix). Studies with these agents are promising but they are not approved in neonates (Prilosec and Prevacid are approved in children >1 year of age). As with the H₂ blockers, there is an increased risk of infections. See doses in Chapter 148.

   4. Diffuse ulcerative esophagitis, gastritis, and duodenal mucosa lesions. Treatment is supportive (maintain adequate oxygenation; nasogastric suction plus the use of IV H₂ blockers is recommended). Acid-reducing agents are sometimes used prophylactically in high-risk patients to reduce the risk. Surgery is rarely needed.

   5. Allergic colitis. Eliminate the formula and change to a hypoallergenic formula.

   6. Nasogastric trauma. May occur if the NG tube is too large or insertion is traumatic. Use the smallest NG tube possible. Observation is indicated. Because the bleeds are usually minimal, active management is not necessary.

   7. Necrotizing enterocolitis. Severe cases of NEC cause upper GI bleeding.

   8. Coagulation disorders. See Chapter 87.

      1. Hemorrhagic disease of the newborn. When vitamin K deficiency is suspected, vitamin K should be administered IV or subcutaneously. Intramuscular injection can result in severe hematoma. One milligram of vitamin K IV stops the hemorrhage within 2 hours. There are 3 forms of vitamin K deficiency:

         1. Early form (first day of life) is related to maternal medications affecting production of vitamin K by the neonate (barbiturates, phenytoin, rifampin, isoniazid, warfarin).

         2. Classic form between days 2 and 7 of life is more commonly seen in infants with inadequate intake of breast milk and when an infant has not received vitamin K at birth (eg, home delivery).

         3. Late form occurs between 2 weeks and 6 months of age. This is secondary to inadequate vitamin K intake (breast-fed infants) or hepatobiliary disease.

      2. DIC. Associated with bleeding from other sites. Coagulation studies are abnormal (increased PT and PTT with decreased fibrinogen levels). Treat the underlying condition and support blood pressure with multiple transfusions of colloid as needed. Platelets may be required. The cause of DIC (eg, hypoxia, acidosis, bacterial or viral disease, toxoplasmosis, NEC, shock, or erythroblastosis fetalis) must be investigated. Several obstetric disorders, including abruptio placentae, chorioangioma, eclampsia, and fetal death associated with twin gestation, may give rise to DIC.

      3. Congenital coagulopathies. The most common that present with bleeding are secondary to factor VIII deficiency (hemophilia A) and factor IX deficiency (hemophilia B). Specific laboratory testing and appropriate consultation with a pediatric hematologist are appropriate.

   9. Drug-induced bleeding. The drug responsible for the bleeding should be stopped, if possible.

   10. Congenital defects such as gastric volvulus, malrotation with volvulus, Hirschsprung disease with enterocolitis, gastric duplication. Urgent surgical consultation is recommended.

   11. Pyloric stenosis. Hydration and surgical pyloromyotomy are necessary.

   12. GI bleeding from liver disease

       1. Octreotide (Sandostatin). Dosage recommended (safety and dosing not firmly established) is 1 mcg/kg IV bolus, followed by 1 mcg/kg/h IV infusion. If no bleeding occurs in 12 hours, decrease the dose by 50%. Then stop the medication when the dose is 25% of the initial dose.

       2. Vasopressin (Pitressin). Used in neonates but has many adverse effects, so it not recommended.