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Luke Gessel, MD Appreciation to: Trent Taylor MD and Sarita Gayle MD. Management Gastrointestinal Bleeding. Outline. Introduction Upper GI Bleed (UGIB) Variceal Bleeding Peptic Ulcer Disease Lower GI Bleed (LGIB) Diverticular Bleeding. Treatment General Measures Blood Products
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Luke Gessel, MD Appreciation to: Trent Taylor MD and SaritaGayle MD Management Gastrointestinal Bleeding
Outline • Introduction • Upper GI Bleed (UGIB) • Variceal Bleeding • Peptic Ulcer Disease • Lower GI Bleed (LGIB) • Diverticular Bleeding • Treatment • General Measures • Blood Products • Pharmacologic Treatments • Endoscopic Treatments • Surgical Treatments • Salvage Treatments
What is Upper GI Bleeding? • Proximal to the Ligament of Treitz • Hematemesis • Coffee-Ground Emesis • Melena • Hematochezia
UGI Bleed Etiologies Center for Ulcer Research and Education Hemostasis Research Group 935 patients admitted to UCLA and West LA VA Medical Centers, 1996
Suspected Variceal Bleeding • How do we know? • History • Alcohol Abuse • Previous Liver Disease • Prior Variceal Hemorrhage • Objective findings • Presence of ascites or hepatic encephalopathy • Spider angiomata/telangiectasias • Cirrhotic labs: low albumin, low platelets, elevated bilirubin, elevated INR
Management of Variceal Bleeding • ICU Admission • ABCs • Venous Access
Variceal Bleeding • General measures • Admit to ICU • ABCs • Venous Access • Initial resuscitation • Hemodynamic Stability • Goal Hgb8 g/dL • Correction of Coagulopathy • Appropriate Pharmacologic Therapy
Variceal Bleeding – ABC’s • Airway/Breathing • Selectively consider intubation • “Patients with ongoing, significant hematemesis or those who may not be able to protect their airway for any reason and are at risk for aspiration should be considered for endotracheal intubation before undergoing endoscopy” - ASGE Guideline GIE 2004
Variceal Bleeding – ABC’s • Circulation • Adequate resuscitation and stabilization is essential prior to endoscopy to minimize treatment-associated complications • 2 Large Bore PIVs (16 gauge or larger) +/- cordis • Central line alone is not enough, need a short and wide catheter • Poiseuille’s law
Hemodynamic stability • IV Fluid Resuscitation • RBC Transfusions up to a point • Goal Hbg ~ 8 g/dL • Restitution of blood loss > Hgb 8 g/dL • Increased Portal Pressure (higher than baseline) • Increased Re-bleeding • Increased Mortality. • Platelet transfusion in the appropriate situation Kravetz D et al. Gastroenterology 1986; 90: 1232-1240. Castaneda B et al. Hepatology 2001; 33: 821-825.
How much to transfuse? • Villenueva et al NEJM 2013 • 921 patients with severe GIB randomized to restrictive (transfuse only when Hgb <7) or liberal strategy (transfuse for Hgb <9) • A restrictive transfusion strategy reduced the risk of further bleeding, the need for rescue therapy, and the rate of complications and increased the rate of survival
Variceal Bleeding – ABC’s • Circulation • Correct Coagulopathies • INR <2 generally considered ideal • FFP standard therapy for acute correction • Factor VIIa not helpful • Multicenter RCT of recombinant factor VIIa in cirrhotic patients with GI hemorrhage failed to show a beneficial effect of recombinant factor VIIa over standard therapy
Variceal Bleeding - Octreotide • Early Pharmacologic Therapy • Octreotide • Causes splanchnic vasoconstriction decreased portal blood flow • Inhibits release of vasodilatory peptides (glucagon) • Local vasoconstrictive effects • 50 mcg IV bolus followed by 50 mcg/h x 3-5 days
Variceal Bleeding - Octreotide • Octreotide efficacy controversial • Corley et al, 2001 Meta analysis • Octreotide improved control of variceal hemorrhage compared with: • All alternative therapies (other somatostatin analogues, sclerotherapy) combined (RR 0.63; CI 0.51-0.77) • Vasopressin/terlipressin (RR 0.58; CI 0.42-0.81) • No additional intervention/placebo (RR 0.46; 0.32-0.67) • Gotzsche et al, 2005 Meta analysis • Somatostatin analogues showed generally negligible beneficial effect • 21 trials with 2588 patients • Did not reduce mortality significantly • Use saved ½ unit of blood per patient • Re-bleeding not significantly reduced in trials with low bias • Substantially reduced in other trials
Variceal Bleeding - Octreotide • AASLD Practice Guidelines, 2007 • “Pharmacologic therapy (somatostatin or its analogues octreotide and vapreotide; terlipressin) should be initiated as soon as variceal hemorrhage is suspected and continued for 3-5 days after diagnosis is confirmed” • Class I, Level A
Variceal Bleeding - Antibiotics • AASLD Guidelines, 2007 • Antibiotics should be given to cirrhotics in ANY type of GI bleed (norfloxacin, ceftriaxone) for 7 days • Infections are present in ~20% of pts with cirrhosis who are hospitalized with GI bleeding; up to 50% develop an infection while hospitalized • A systematic review of eight placebo-controlled trials with a total of 864 patients found the antibiotics were associated with a significant reduction in mortality (RR 0.75, 95 percent CI 0.55 to 0.95) Bernard B et al. Hepatology 1999; 29: 1655-1661. Hou M, et al. Hepatology 2004; 39: 746-753.
Variceal Bleeding - Endoscopy • AASLD Guidelines, 2007 • “EGD, performed within 12 hours, should be used to make the diagnosis and to treat variceal hemorrhage, either with endoscopic variceal ligation (banding) or sclerotherapy”
Variceal Bleeding – Salvage Therapy • For variceal bleeding, 10-20% of patient’s bleeding cannot be controlled with endoscopic and/or pharmacologic therapy • TIPS • Balloon Tamponade • Airway control • Bridging to more definitive therapy (TIPS)
Gastric Variceal Bleeding • Several studies have demonstrated the value of TIPS for uncontrolled bleeding from gastric varices • Control rates over 90% • “The threshold to place TIPS for gastric variceal hemorrhage is lower than for esophageal variceal hemorrhage and TIPS can be recommended if endoscopic therapy is not possible or after a single failure of endoscopic treatment.” -AASLD recommendations 2007
Variceal Bleeding - Disposition • Rebleeding 60% at 1-2 years; Mortality 33% • Beta-blockers shown to decrease rate of rebleeding (but remember side effects!) • Pantoprazole 40 mg per day decreases ulcer size • EGD for banding in 3-4 weeks until varices eradicated decreases rate of rebleeding • If transplant candidate, refer to Transplant Ctr AASLD Practice Guideline 2007
Variceal UGIB Summary • ABCs – Ok to intubate • IV Access • Hg ~7-8 grams/dL • Antibiotics x 7 days (norfloxacin, ceftriaxone) • Octreotide ASAP and EGD within 12 hrs • TIPS vs. Shunt for salvage therapy • Evidence for treatment of gastric varices not as robust – EVL, sclerotherapy, tissue glue, TIPS
Peptic Ulcer Disease • General Measures • ABCs • Venous Access • Surgery Consult? IR? • Initial resuscitation • Pharmacologic therapy • Endoscopic Management
Peptic Ulcer Disease – Acid Suppression • High acid inhibits platelet aggregation • Therefore, inhibiting gastric acid (raise pH to 6 or more) may promote clot stability, thus decreasing the likelihood of rebleeding
Peptic Ulcer Disease – PPI vs. Placebo • Assessed whether the use of a high dose PPI would reduce the frequency of recurrent bleeding after endoscopic treatment of bleeding peptic ulcers. • RCT of 240 pts treated endoscopically for acute GI bleeding from PUD received IV PPI vs placebo followed by oral PPI x 8 weeks Lau et al, NEJM, 2000
Peptic Ulcer Disease – PPI vs. Placebo • Effect of preemptive infusion of omeprazole before endoscopy on the need for endoscopic therapy. • RCT of 638 with UGI bleeding randomized to receive omeprazole or placebo (each as an 80-mg intravenous bolus followed by an 8-mg infusion per hour) before endoscopy the next morning. Lau et al, NEJM, 2007
Peptic Ulcer Disease – PPI vs. Placebo • No difference in: • Blood transfusion • Incidence of recurrent bleeding, • Surgery • 30 day mortality. • More pts in the omeprazole group had hospital stay <3 days • 60.5% vs 49.2% in the placebo group (P = 0.005) • On endoscopy • Fewer patients in the omeprazole group had actively bleeding ulcers (P = 0.01) • More omeprazole-treated patients had ulcers with clean bases (P = 0.001). Lau et al, NEJM, 2007
Peptic Ulcer Disease – PPI vs. Placebo • Conclusions: High-dose infusion of omeprazole at time of admission for 72 hours substantially reduces therisk of recurrent bleeding. • Omeprazole 80 mg IV bolus, followed by 8 mg/hr x 72 hours • Discharge on omeprazole po for 8 weeks Lau, et al, NEJM, 2000 Lau, et al, NEJM, 2007
Peptic Ulcer Disease – PPI • ASGE recommendation: • “We recommend antisecretory therapy with PPIs for patients with bleeding caused by peptic ulcers or in those with suspected peptic ulcer bleeding awaiting endoscopy.”
Peptic Ulcer Disease - Endoscopy • Endoscopy has been shown in randomized studies to lead to a: • Reduction in blood transfusion requirements • Shortened ICU and hospital stays • Decreased need for surgery • Lower mortality rate Barkun A, et al. Ann Intern Med 2003. Spiegel BM, et al. Arch Intern Med 2001.
Peptic Ulcer Disease - Endoscopy • Endoscopic Options: • Thermal coagulation • Injection therapy • Hemostatic clips • Fibrin sealant (or glue) • Argon plasma coagulation • Combined Therapy
Thermal Coagulation Olympus Heater Probe Boston Scientific Gold Probes ACMI BICAP
Hemostatic Clips Olympus QuickClip2 Wilson-Cook TriClip Boston Scientific Resolution Clip
Stigmata of bleeding: Prevalence and risk of rebleeding 55% 43% Risk of rebleeding 22% 10% 5% LaineL, Peterson WL. Bleeding peptic ulcer. N Engl J Med 1994;331:717–27.
PUD Rebleeding Rebleeding occurs in 15-20% of patients 98% occur within 3-4 days after initial episode Predictors of increased risk of recurrent bleeding - Hospitalized patients - Age >60 years - Shock - Comorbidities - Need for transfusion - Fresh blood in emesis, NG lavage or on rectal exam Schlesinger and Fordtran, 2006
PUD Rebleeding • Surgery versus Endoscopy for Rebleeding • Endoscopic hemostasis achieved in 75% • Mortality, duration of hospital stay, duration of ICU stay, volume of transfusion similar • Pts who undergo surgery have more complications
PUD Rebleeding • Transarterial embolization • Embolization agents: Gelfoam, polyvinyl alcohol, cyanoacrylicglues, and coils • Success rates: 52% - 98% Gralnek, GIE, May, 2011 Wong, et al GIE, May, 2011
PUD Rebleeding • Author conclusion: TAE reduces the need for surgery without increasing overall mortality and is associated with fewer complications. • TAE should be considered, if not before, at least as an alternative to surgery in patients with PUD in whom endoscopic hemostasis fails Gralnek, GIE, May, 2011 Wong, et al GIE, May, 2011
Aspirin therapy after PUD bleeding • Should patients who take aspirin to prevent cardiovascular disease continue to take it after an acute UGI bleeding event? • Randomized, placebo-controlled trial of 156 pts with PUD in Hong Kong between 2003 to 2006 • 78 pts rec’d aspirin (80 mg/d) and 78 received placebo for 8 weeks immediately after endoscopy. All pts rec’d IV PPI followed by po PPI. Sung, et al. Annals of Int Med, January, 2010.
Aspirin therapy after PUD bleeding Sung, et al. Annals of Int Med, January, 2010.
Aspirin therapy after PUD bleeding • Authors’ Conclusion: Among low-dose aspirin recipients who had peptic ulcer bleeding, continuous aspirin therapy may increase the risk for recurrent bleeding but potentially reduces mortality rates. Larger trials are needed to confirm these findings. Sung, et al. Annals of Int Med, January, 2010.
PUD - Disposition • Disposition is according to clinical risk and endoscopic risk of rebleeding • All patients require outpatient therapy and close follow-up • Discharge on PPI, but NOT indefinitely • Don’t forget to check Helicobacter pylori and eradicate – AND VERIFY ERADICATION
Non-ulcer causes of UGIB • Esophagitis • Rarely requires endoscopic therapy • Mallory-Weiss tear • Usually self-limited, can require treatment if bleeding ongoing • Dieflafoylesion • Aortoentericfistula • Endoscopy is diagnostic only • CT imaging • Prompt surgery consult • Tumors • High rebleeding rate • surgery often required for hemostasis
Peptic Ulcer Disease - Summary • ABC’s • IV Access • Resuscitation • Surgery Consult? • PPI before and after endoscopy • Endoscopy • Within 24h for high-risk patients • Remember to look for the etiology (NSAIDs, H.Pylori, other)
ABIM Board Review Question • A 72 year old woman is brought to the ED after having vomited a large amount of blood. She has had mild upper abdominal pain and low-grade fevers for several weeks. Medical history is significant for systolic hypertension and repair of an abdominal aortic aneurysm. Current medications are simvastatin, metoprolol, HCTZ and low-dose aspirin. • PE: Pale, clammy and weak. T T38.2, HR 105, BP 85/60. Abdominal exam: mid-epigastric tenderness w/o rebound/guarding. BS nl Rectal exam: black, tarry stool • Labs: • Hgb10.9 g/dL • WBC 13,400/µL • BUN 40 mg/dL • Serum creat 1.2 mg/dL MKSAP 14