GI Bleeding, Liver Failure and Pancreatitis

In depth

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Upper GI bleeding: risk scores and resuscitation

Peptic ulcer is the leading upper GI source, then varices, erosive disease, Mallory-Weiss tears and angioectasia. As little as 50–100 mL of blood can cause melena, and digested blood raises the BUN; a BUN/creatinine ratio above 30 favors an upper source (Srygley 2012).

Transfuse at 7 g/dL, about 8 with cardiovascular disease (ACG 2021). Villanueva 2013 (921 patients, 7 vs 9 g/dL) found better 6-week survival (95% vs 91%) and less rebleeding (10% vs 16%) with restriction; the survival gain was in Child-Pugh A and B cirrhosis, and portal pressure rose only in the liberal arm.

Erythromycin 250 mg IV 30–120 min before endoscopy clears the stomach (check the QTc). Pre-endoscopic PPI downstages stigmata without changing outcomes; ACG 2021 made no recommendation either way. Endoscopy within 24 h is the target; sooner did not help in Lau 2020 (516 patients, Glasgow-Blatchford ≥12: 30-day mortality 8.9% within 6 h vs 6.6% at 6–24 h). Tranexamic acid failed in HALT-IT (2020, 12,009 patients): death from bleeding 4% in both arms, venous thromboembolism 0.8% vs 0.4%.

Endoscopic stigmata, rebleeding and lower GI bleeding

Bipolar or heater-probe coagulation, clips and absolute ethanol work; epinephrine injection needs a second method. After hemostasis, give high-dose PPI for 3 days (80 mg IV, then 8 mg/h or intermittent boluses), then oral PPI twice daily to day 14. Rebleeding gets repeat endoscopy (over-the-scope clips), then transcatheter embolization (ACG 2021), with surgery last. Retest a negative H. pylori result, because acute bleeding causes false negatives.

Lower GI bleeding is most often diverticular and usually stops on its own. In hematochezia with shock, exclude an upper source first (about 10–15%, ACG 2016); a shock index (HR/SBP) above 1 marks instability (BSG 2019). An Oakland score of 8 or less predicts a 95% chance of safe discharge (Oakland 2017). For ongoing hemodynamically significant bleeding, ACG 2023 suggests CT angiography first and embolization if it is positive; other inpatients get a nonurgent colonoscopy after bowel preparation, because colonoscopy within 24 h has not reduced rebleeding or death.

Portal hypertension and acute variceal bleeding

Portal pressure gradient = flow × resistance. Fibrosis fixes most intrahepatic resistance; stellate-cell contraction (low nitric oxide, high endothelin) adds a dynamic part. Splanchnic vasodilation raises inflow and creates a hyperdynamic, sodium-retaining circulation. Variceal wall tension rises with pressure and diameter (Laplace), so large varices with red wale marks rupture, and overfilling raises portal pressure.

The hepatic venous pressure gradient (HVPG), wedged minus free hepatic venous pressure, reflects sinusoidal pressure and misses presinusoidal disease such as portal vein thrombosis.

Nonselective beta-blockers cut cardiac output (β₁) and splanchnic inflow (unopposed α after β₂ blockade); carvedilol's α₁ blockade also lowers intrahepatic resistance. Baveno VII prefers carvedilol for CSPH after PREDESCI (decompensation or death 16% vs 27%) and reduces or stops beta-blockers with ascites if SBP falls below 90, MAP below 65, or HRS-AKI develops.

Octreotide, the US agent, is 50 mcg IV, then 50 mcg/h; terlipressin is 2 mg IV every 4 h for 48 h, then 1 mg every 4 h. Pre-emptive TIPS within 72 h, ideally 24 h, is for Child-Pugh C 10–13, Child-Pugh B 8–9 with active bleeding at endoscopy, or HVPG above 20 (Baveno VII); ACLF, HE or jaundice at admission do not exclude it. In García-Pagán 2010 (63 patients), it kept 97% vs 50% free of failure or rebleeding at 1 year and raised 1-year survival from 61% to 86%.

TIPS may be futile at Child-Pugh 14–15, or MELD above 30 with lactate above 12 mmol/L, unless transplant is near (Baveno VII). Six-week mortality was 16% in Reverter 2014. Secondary prophylaxis is a beta-blocker plus band ligation.

TIPS and balloon tamponade

TIPS joins a hepatic vein to a portal branch with a covered 8–10 mm stent, aiming for a portal pressure gradient below 12 mm Hg (Baveno VII); it loads the right heart and diverts ammonia past the liver. Heart failure, severe pulmonary hypertension, uncontrolled sepsis and unrelieved biliary obstruction contraindicate it (AASLD 2010). MELD was first built to predict death after elective TIPS (Malinchoc 2000).

• Overt HE in roughly 20–50%, more with wider stents, older age and prior HE
• Pulmonary edema or right heart strain as preload rises
• Neck hematoma; hemoperitoneum from capsular puncture
• Rising bilirubin, hemolysis, fever (stent infection); Doppler checks patency

Balloon tamponade compresses inflow at the gastroesophageal junction; rebleeding on deflation is common, so it only bridges to TIPS. Baveno VII rates esophageal stents as equally effective and safer (Escorsell 2016, 28 patients: bleeding control 85% vs 47%, serious adverse events 15% vs 47%).

1. Intubate; test both balloons, recording the pressure at each 100 mL of air
2. Insert by mouth to at least 50 cm; partly inflate the gastric balloon and confirm it below the diaphragm on x-ray
3. Finish inflating in steps; a pressure 15 mm Hg above the pre-insertion value means esophageal placement
4. Pull up to the gastroesophageal junction and apply light traction (about 0.5–1 kg)
5. Esophageal balloon only for continued bleeding: 30–45 mm Hg by manometer
6. Mark the tube at the lips and check hourly; suction above the esophageal balloon
7. Scissors at the bedside: for airway obstruction, cut all lumens and pull the tube
8. Remove within 24 h (Baveno VI)

Cirrhosis complications: ascites, SBP, HRS and encephalopathy

Tap new ascites and every admitted patient with ascites (AASLD 2021). A serum–ascites albumin gradient of 1.1 g/dL or more means portal hypertension; ascitic protein below 1.5 g/dL raises SBP risk. Give 2 g sodium a day with spironolactone 100 mg and furosemide 40 mg (up to 400 and 160 mg), and albumin 6–8 g per liter for paracentesis over 5 L. Routine plasma or platelets before paracentesis are not needed.

SBP is an ascitic neutrophil count of 250/mm³ or more; inoculate blood culture bottles at the bedside. Two of protein above 1 g/dL, glucose below 50 mg/dL and LDH above the serum normal, or polymicrobial growth, suggest surgical peritonitis. Give cefotaxime or ceftriaxone plus albumin 1.5 g/kg at diagnosis and 1 g/kg on day 3 (Sort 1999: renal impairment 10% vs 33%, in-hospital death 10% vs 29%).

HRS-AKI (ICA 2015 criteria, used by AASLD 2021) needs cirrhosis with ascites; creatinine up 0.3 mg/dL in 48 h or 50% in 7 days; no response to 2 days of diuretic withdrawal and albumin 1 g/kg/day; no shock or nephrotoxins; and no proteinuria over 500 mg/day, hematuria or abnormal ultrasound. ADQI–ICA 2024 adds urine output and drops the mandatory 48-h albumin challenge.

Terlipressin, a V₁ agonist, reversed HRS in 32% vs 17% in CONFIRM (2021, 300 patients), but 11% vs 2% died of respiratory disorders. Label dose: 0.85 mg IV every 6 h, raised to 1.7 mg on day 4 if creatinine has fallen less than 30%, for up to 14 days; benefit is unlikely above creatinine 5 mg/dL. Norepinephrine 0.5–3 mg/h is the alternative (ADQI–ICA 2024); transplant is definitive.

Find the trigger: infection, bleeding, dehydration, hypokalemia, constipation, sedatives or TIPS. A high ammonia adds nothing diagnostic in cirrhosis, but a normal one should prompt a search for another cause (AASLD–EASL 2014). Give lactulose 25 mL every 1–2 h until two soft stools, then 2–3 a day; rifaximin 550 mg twice daily cut breakthrough HE from 45.9% to 22.1% (Bass 2010), and 4 L of PEG 3350 beat lactulose at 24 h (HELP 2014: 91% vs 52%). Keep protein at 1.2–1.5 g/kg/day.

Acute-on-chronic liver failure grade 3 (three or more organ failures) carried 77% 28-day mortality in CANONIC (Moreau 2013). Raising albumin to 3 g/dL in inpatients did not reduce infection, kidney dysfunction or death (ATTIRE 2021: 29.7% vs 30.2%) and caused more serious adverse events.

Acute liver failure: causes, prognosis and transplant

Acute liver failure is an INR of 1.5 or more with any encephalopathy, without cirrhosis, in an illness under 26 weeks (AASLD 2011). Hyperacute ALF (jaundice to HE within 1 week: acetaminophen, viral, ischemic) has the most cerebral edema but the best spontaneous recovery; subacute ALF (4–12 weeks: drugs, indeterminate) is the reverse (O'Grady).

King's College criteria (O'Grady 1989), acetaminophen: arterial pH below 7.30 after fluids, or INR above 6.5 plus creatinine above 3.4 mg/dL plus grade 3–4 HE; Bernal 2002 added lactate above 3.5 mmol/L at 4 h or 3.0 at 12 h. Other causes: INR above 6.5, or three of age under 10 or over 40, drug or indeterminate cause, jaundice over 7 days before HE, INR above 3.5 and bilirubin above 17.5 mg/dL. They are specific but insensitive (sensitivity 68%, specificity 82% in non-acetaminophen ALF, McPhail 2010).

Astrocytes turn ammonia into glutamine and swell; intracranial hypertension developed in 55% of patients with arterial ammonia above 200 µmol/L (Bernal 2007). Intubate at grade 3; keep HOB 30°, PaCO₂ 34–42 mm Hg and normothermia, check glucose every 1–2 h, and start CRRT early. Murphy 2004 held sodium at 145–155 mmol/L with hypertonic saline; EASL 2017 keeps 140–145, treats surges with hypertonic saline or mannitol, and adds brief hyperventilation to PaCO₂ 25–30 if they resist; lactulose has no role. ICP monitors did not improve 21-day survival in ALFSG data (33% vs 38%; bleeding in 7%; Karvellas 2014).

The INR overstates bleeding risk: thromboelastography was normal in 63% despite a mean INR of 3.4 (Stravitz 2012). EASL 2017 advises against prophylactic plasma or platelets, which risk thrombosis and lung injury and erase the INR trend used for transplant decisions; correct only for bleeding or procedures.

Contact a transplant center once INR exceeds 1.5 with any HE (EASL 2017). For transfer with evolving HE, intubate and sedate first, keep vasopressors drawn up and carry mannitol in case the pupils dilate en route. UNOS Status 1A requires HE within 56 days of first symptoms, no prior liver disease, ICU care, and ventilation, dialysis or INR above 2.0 (OPTN Policy 9.1.A). High-volume plasma exchange improved hospital survival (58.7% vs 47.8%, Larsen 2016). Uncontrolled sepsis, fixed dilated pupils and severe cardiopulmonary disease weigh against transplant.

Alcohol-associated hepatitis

NIAAA 2016: jaundice within 8 weeks of heavy drinking, bilirubin above 3 mg/dL, AST above 50 IU/L with AST:ALT above 1.5, both below 400. Screen for infection (cultures, chest x-ray, paracentesis) before steroids.

Prednisolone is 40 mg daily for 28 days. STOPAH (2015, 1,103 patients) found 28-day mortality of 14% vs 17% with placebo (OR 0.72, p=0.06), no benefit at 90 days, more serious infections (13% vs 7%) and nothing from pentoxifylline. Steroids helped at 30 days only at MELD 21–51, most at 25–39 (Arab 2021, 3,380 patients). IV NAC added to prednisolone lowered 1-month (8% vs 24%) but not 6-month mortality (Nguyen-Khac 2011). Early transplant for selected nonresponders gave 6-month survival of 77% vs 23% (Mathurin 2011); a Lille score of 0.45 or more had predicted 6-month survival of 25% vs 85% (Louvet 2007).

Feed 35–40 kcal/kg and 1.2–1.5 g/kg of protein a day (AASLD–EASL 2014 targets), give thiamine before glucose, and treat alcohol use disorder: abstinence decides long-term survival.

Acute pancreatitis: severity, fluids and nutrition

Trypsin activated inside acinar cells causes autodigestion, SIRS and capillary leak; a rising hematocrit and BUN mark third-spacing. The revised Atlanta classification (Banks 2013) grades severity by organ failure.

BISAP gives a point each in the first 24 h for BUN above 25 mg/dL, impaired mentation, SIRS, age above 60 and pleural effusion; mortality runs from under 1% to over 20% (Wu 2008). ACG 2024 warns that no score predicts severity reliably and advises against CT on admission just to stage it.

WATERFALL (2022, 249 patients) compared aggressive lactated Ringer's (20 mL/kg, then 3 mL/kg/h) with moderate (10 mL/kg only if hypovolemic, then 1.5 mL/kg/h) and stopped early: fluid overload 20.5% vs 6.3%, with no fewer moderately severe or severe cases (22.1% vs 17.3%). ACG 2024 suggests moderate, goal-directed Ringer's, reassessed within 6 h, aiming for a falling BUN.

ACG 2024 suggests low-fat solid food within 24–48 h as tolerated, enteral over parenteral nutrition when needed, and no prophylactic antibiotics. In PYTHON (2014, 208 patients), tube feeding within 24 h was no better than oral diet at 72 h (infection or death 30% vs 27%). Urgent ERCP is for cholangitis only (APEC 2020: 38% vs 44%), and same-admission cholecystectomy cut gallstone readmissions (4.7% vs 16.9%, PONCHO 2015). Treat pain with opioids and check ionized calcium and glucose.

Necrotizing pancreatitis and abdominal compartment syndrome

Infection of necrosis appears after the first week with fever, rising WBC, new organ failure or gas on CT. Give antibiotics that penetrate necrosis (carbapenem, quinolone or metronidazole) and delay intervention, preferably 4 weeks, until the collection is walled off (ACG 2024). Endoscopic transgastric drainage, often with lumen-apposing metal stents, avoids external pancreatic fistulas.

WSACS 2013: intra-abdominal hypertension is sustained IAP of 12 mm Hg or more (grade I 12–15, II 16–20, III 21–25, IV over 25); abdominal compartment syndrome is IAP above 20 with new organ dysfunction. Abdominal perfusion pressure is MAP minus IAP, and the renal filtration gradient is roughly MAP minus twice the IAP, so oliguria comes early.

1. Patient supine and flat; head elevation raises the reading
2. Zero the transducer at the midaxillary line at the iliac crest
3. Instill no more than 25 mL of sterile saline into the bladder
4. Wait 30–60 s for detrusor relaxation; read at end-expiration, in mm Hg

Then decompress the gut, drain ascites or collections, deepen analgesia and sedation, avoid a positive fluid balance, and decompress surgically if organ failure persists (WSACS 2013).

Exam pearls

• Transfuse GI bleeding at Hgb 7 (about 8 with heart disease); overtransfusion raises portal pressure
• Variceal bleed: octreotide and ceftriaxone before endoscopy, ligation within 12 h; no FFP to fix the INR
• Pre-emptive TIPS within 72 h for Child C 10–13 or Child B 8–9 with active bleeding
• Balloon tamponade: intubate, x-ray before full inflation, scissors at the bedside, out within 24 h
• SBP: neutrophils ≥250/mm³; cephalosporin plus albumin 1.5 g/kg day 1 and 1 g/kg day 3
• Terlipressin for HRS needs SpO₂ ≥90% and no volume overload
• HE: lactulose to 2–3 soft stools daily, rifaximin for recurrence, no protein restriction
• ALF: INR ≥1.5 plus encephalopathy without cirrhosis; frequent glucose, HOB 30°, early transplant call
• Pancreatitis: severe means organ failure over 48 h; moderate Ringer's, early feeding, no prophylactic antibiotics
• Bladder pressure: ≤25 mL saline, supine, end-expiration; ACS is IAP over 20 with new organ failure