Upper Gastrointestinal Bleeding - Angelfire · Upper Gastrointestinal Bleeding Audis Bethea,...
Transcript of Upper Gastrointestinal Bleeding - Angelfire · Upper Gastrointestinal Bleeding Audis Bethea,...
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Upper Gastrointestinal Bleeding
Audis Bethea, Pharm.D.
Assistant Professor
Therapeutics IV
April 13, 2004
Upper Gastrointestinal BleedingOccurs in approximately 100 cases per 100,000 adults per year
Overall mortality from acute GI bleeding is approximately 6-7%
Mortality rates approach 30% for upper GI bleeds due to varices
Mortality rates may confounded by concomitant diseases present in patients who present with gastrointestinal bleeds
Bleeding occurring from one of the following organsEsophagusStomachDuodenum
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Esophageal Bleeding
Mallory-Weiss tearsMost common cause of all upper GI bleeds Longitudinal tears caused by retching
Erosive esophagitisResult of severe gastroesophageal reflux disease (GERD)
Esophageal varicesResult of portal hypertension
Stomach and Duodenal BleedingGastric varices
Most common cause of gastric bleedingResult of portal hypertension
Peptic ulcersSecond leading cause of gastric bleedingSevere peptic bleeds result in mortality rates of 10-25%
Stress related mucosal lesions (Stress ulcers)Injury to gastric mucosa secondary to elevated physiologic stressGastric erosions are present in approx. 90% of patients by the third ICU day
Duodenal ulcer / duodenitisMost often associated with H. pylori overgrowth/infection
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Upper Gastrointestinal Bleeding
OvertMelenaHematocheziaBloody gastric aspirateHematemesis
Clinically significant bleedingAny or all of the above resulting in significant blood loss requiring clinical intervention
Management of Upper GI Bleed
StabilizationABCsIntubationAssessment of cardiovascular statusIntravenous accessFluid resuscitationLaboratory parameters
• BMP, CBC, coagulation panel
DiagnosisEndoscopic examSedation and/or analgesia
• Benzodiazepines• Opiates
TreatmentDepends on the source of the bleedContinue cardiovascular stabilization Empiric therapy targets ulcer and variceal bleeds
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Management of Upper GI Bleed
LethargicConfusedAgitatedAnxious Mental Status
< 55 – 1520 – 30> 30Urine output (mL/hr)
DecreasedDecreasedNormalNormal Supine blood pressure
> 140> 120> 100< 100 Pulse rate
> 40%30 – 40%15 – 30%< 15%% Loss of volume
Class IVClass IIIClass IIClass IParameter
Management of Upper GI Bleed
Whole blood RV = VDColloid = 1.5 X VD
Crystalloid RV = 4 X VD
Determine resuscitation volume (RV)
VD = BV X % lossCalculate volume deficit (VD)
Refer to previous slideEstimate % loss of blood volume
Whole blood Male = 66 mL/kg, female = 60 mL/kg
Estimate normal blood volume
DescriptionSequence
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Management of Upper GI BleedFluid resuscitation
Crystalloids (Normal saline, lactated ringers)• Isotonic fluids freely distribute; 3:1 extravascular to intravascular space• Requires large amounts of fluid to achieve adequate volume expansion
Colloids (Dextran, albumin, and hetastarch)• Large oncotically active molecules that are relatively impermeable to vasculature• Expand vascular volume 2 to 4 times more than that of crystalloids• Colloids have no advantage over crystalloids in reducing mortality
Blood products• Used only to supplement intravenous fluids
– One unit of packed RBCs increases Hgb by approximately 1 g/dL and Hct by 3%• Usually not necessary for Class I or Class II hypovolemia
Non-variceal Esophageal Lesions
Mallory-Weiss tearsBleeding typically subsides spontaneously after retching stopsPersistent bleeding
• Cauterization via endoscopy• Prevention of acid secretion via H2-antagonist or proton pump
inhibitors (PPI)• Antiemetics to prevent retching / emesis
No formal algorithms or recommendations exist
Erosive esophagitisAntisecretory therapy to increase gastric pH See PUD / GERD lectures
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Variceal LesionsDefinition
Tortuous, collateral vessel that forms in response to ↑ portal pressureVarices divert blood flow from the portal vein, lowering portal pressure
EpidemiologyApproximately 40–60% of patients with cirrhosis develop gastroesophageal varicesEsophageal and gastric varices account for approximately 30 % upper GI bleedsUp to 30% of initial variceal bleeds are fatal70% of patients will have recurrent variceal bleedsOne-year survival rate following variceal bleed is 32-80%
Etiology of Variceal LesionsCirrhosis
Impeded hepatic flowPortal Hypertension
Dilation of portal vascular channelsDilated vascular channels
Portosystemic collateral vessels (varices)Varices
Shunt blood away from portal vein
Risk factors for variceal bleedSeverity of liver diseaseContinued alcohol consumption Varix sizeElastic properties of the vesselIntravariceal pressureVariceal wall tension
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Management of Variceal Bleeds
Fluid resuscitationCrystalloids, colloids, and blood products
Endoscopic therapyInjection sclerotherapy
• 70-80% efficacy for acute bleeds• Numerous complications
Variceal ligation (banding)• Bands wrapped around esophageal
mucosa• 70-80% efficacy for acute bleeds• Fewer complications
Management of Variceal Bleeds
Balloon tamponadeApplies direct pressure to bleeding varixBridge therapy in patients w/ excessive bleeding↑ incidence of complications
• Esophageal laceration or rupture
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Pharmacologic Therapy of Variceal BleedsVasopressin
Endogenous peptide, also known as antidiuretic hormone (ADH)Stimulates V1 receptors in smooth muscle of vasculature
• ↓ splanchnic blood flow of organs feeding into the portal system; ↓ portal pressureSystemic vasoconstriction → myocardial and mesenteric ischemia limits use The addition of nitroglycerin infusion improves efficacy and ↓ side effects
DosingVasopressin → 30-40 units bolus over 30-40 min.; continuous infusion 0.4-0.8 u/minNitroglycerin → initiate infusion at 40-50 mcg/min; titrate up to 400 mcg/min
• *Maintain SBP ≥ 100 mmHg*
Pharmacologic Therapy of Variceal Bleeds
OctreotideSynthetic analogue of the naturally occurring peptide somatostatin
• Secreted by the hypothalamus, pancreas, and gastrointestinal tractInhibits the secretion of numerous hormones:
• Pituitary gland → growth hormone• Pancreas → insulin and glucagon• Gastrointestinal tract → gastrin, gastric acid, pepsin, and cholecystekinin• Nervous system → substance P
Mechanism of actionInhibits variceal bleeding by reducing splanchnic blood flow and portal pressure
• Prevention of postprandial hyperemia• Inhibition of vasodilatory effects of substance P and glucagon
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Pharmacologic Therapy of Variceal BleedsOctreotide
Randomized, controlled trials have found octreotide to be more effective vs. vasopressin with substantially fewer adverse effectsTypically used in conjunction with endoscopic therapy
Dosing50 mcg bolus (IVP); continuous infusion of 25-50 mcg/hr x 24-48 hoursBreakthrough bleeding → additional 50 mcg bolus; ↑ rate to 50 mcg/hour
Adverse effectsHyperglycemia, abdominal cramping, bradycardia, and biliary congestion
IV preparation1200 mcg in 250 mL of diluent (normal saline)Stable for up to 48 hours when stored at room temperature or refrigerated
Surgical Treatment of Variceal Bleeds
Salvage therapy with failure of endoscopic or pharmacologic therapy
Portosystemic shuntCompletely bypasses liver
Transjugular intrahepatic portosystemicshunt (TIPS)
Implanted into the liver bypassing the liverRisk of rebleed is 8-18% per yearIncreases risk of hepatic encephalopathyStenosis occurs in about 50% of patients within 2 years
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Management of Peptic Ulcers
Fluid resuscitation measuresCardiovascular stabilizationAssessment of precipitating cause (ex. NSAIDs)Pharmacological management → identical to treatment for bleeding stress ulcer
Stress Ulcers and GastritisDefinition
Acute superficial inflammatory lesion of the gastroduodenal mucosa • Associated with abnormally elevated physiologic demands
EpidemiologyEndoscopic evidence of stress gastritis is evident within 24 hours of admissionGastric erosions are present in approx. 90% of patients by the third ICU dayGastrointestinal bleeding occurs in up to 50 - 70% of critically ill patientsClinically significant bleeds occur in 5-30% of patients with stress gastritis Mortality rates from clinically significant bleeds approach 50%
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Stress Ulcers and Gastritis
EtiologyAlteration in gastric mucosal defense
• Reduced perfusion of gut mucosalDecreased delivery of bicarbonate and adenosine triphosphate to gut mucosa
• Generation of oxygen-derived free radicalIntraluminal acid
• Impaired perfusion results in impaired removal of gastric acid from the mucosa and back diffusion of hydrogen ions
Breakdown of gastric mucosal barrier
Formation of Stress Ulcers and GastritisGut Mucosal Ischemia
Impaired Protective Mechanisms↓ Prostaglandin Production
↓ Mucous / bicarbonate barrier
↓ H+ back diffusion
↓ Epithelial removal
↓ Mucous / bicarbonate barrier
Gastrointestinal Bleed
Acid Secretion
?? H. Pylori
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Risk Factors for Stress Ulcers and Gastritis
Mechanical ventilation
Sepsis
Coagulopathy / anticoagulation
Burn patients
Renal failure
Age > 65 years
Corticosteroid therapy / NSAIDS
Recent history of gastric ulcers / bleed
Head trauma / bleed
Anaphylaxis
Severe polytrauma
Ileus or other gastroenterologic disease
Renal disease
SBP < 100 mmHg for > 1 hour
Stress ulcers vs. Peptic Ulcer DiseaseStress ulcers
Often asymptomaticSuperficialLocated in acid producing areasRarely perforateUsually produce superficial bleeding
Peptic ulcer diseaseSymptomaticDeep, well definedDuodenal bulb, gastric antrum Commonly perforateExtensive bleeding from exposed vessel(s)
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Stress Ulcers: Preventive Strategies
Preservation of mesenteric blood flowMaintain systemic perfusion and Do2
Enteral nutrition Reduce risk of stress ulcer bleeding
• Maintains functional integrity of gut
PharmacologicCytoprotective agents
• SucralfateAntacidsAntisecretory agents
• H2-antagonists• Proton pump inhibitors
Cytoprotective Agent: Sucralfate
Cytoprotective agent → helps maintain integrity of gastric mucosaComplexes w/ gastric secretions forming a viscous, adhesive paste Viscous paste forms a protective coating from gastric secretions
DosingProphylaxis → 1g PO/per tube q6 hours Treatment → 1g PO/per tube q4-6 hoursMix with 10mL sterile water to administer per tube
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Cytoprotective Agent: SucralfateAdvantages
Lower risk of gastric bacterial colonization → ↓ risk of aspiration pneumoniaInexpensive
DisadvantagesLower rate of clinically significant bleeding with acid suppression vs. sucralfate
Adverse EffectsConstipationAluminum toxicity; CNS manifestations (seizures, encephalopathy, and myoclonus)Requires enteral administrationIncreases in gastric pH decrease efficacyDifficult to administer via feeding tubes with small lumens Drug-drug interactions
The Role of Acid Suppression Therapy
Pepsin destruction8
Clot stabilization (↓ frequency of rebleeding)7
↑ platelet aggregation and polymerization of fibrin5 – 7‡
99.9% neutralization of gastric acid5
Pepsin inactivation> 4†
Decreased frequency of bleeding episodes> 3.5
Clinical effectpH
† Goal of acid suppression therapy for GI prophylaxis‡ Goal of acid suppression therapy for active non-variceal upper GI bleeds
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Acid Suppression Therapy: Antacids
AntacidsNeutralization of gastric acidity resulting in ↑ gastric pH
DosingProphylaxis
• Give 30 mL of antacid formulation and check gastric pH in 1 hour• If pH < 4.0 give 60 mL antacid and check pH in 1 hour• Repeat step 2 until gastric pH is > 4.0• Give maintenance antacid doses every 1-2 hours
Treatment → no role in the treatment of acute non-variceal upper gastrointestinal bleeds
Acid Suppression Therapy: Antacids
AdvantagesAllows quantitative assessment of efficacy via measurement of gastric pHLow cost
DisadvantagesRequires enteral administrationRequires frequent administration of large doses to obtain optimal acid suppressionIncreased risk of aspiration pneumoniaElectrolyte abnormalitiesConstipation / diarrheaDrug - drug interactionsDecreased absorption of quinolones, tetracycline, and thyroid supplements
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Antisecretory Therapy: H2-AntagonistsAntisecretory activity increases gastric pH
Competitive inhibition of histamine-2 receptors of the gastric parietal cells • Reduces gastric acid secretion and hydrogen ion concentration
Dosing
IV → 20 mg bolus, followed by continuous infusion of 1.7 mg/hr
PO/per tube → 20 mg q12 hIV → 20mg q12 h
Famotidine
IV → 50 mg bolus, followed by continuous infusion of 6-8 mg/hr
*PO/per tube → 150 mg q12 hIV → 50 mg IV q 8 hours
Ranitidine
TreatmentProphylaxisAgent
Antisecretory Therapy: H2-Antagonists
AdvantagesIV and enteral administrationAllows quantitative assessment of efficacy via measurement of gastric pH
DisadvantagesIncreased risk of aspiration pneumonia
ToleranceCumulative effect, ↑ exposure results in decreased activity> 24 hours of exposure to treatment doses results in significant tolerance Theorized that tachyphylaxis is due to an increase in histamine activity
Adverse EffectsThrombocytopenia, CNS
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Antisecretory Therapy: PPI
Antisecretory effects increase gastric pH
Activated in the vesiclular compartment of parietal cells
Irreversible binding inactivates Na+/K+
ATPase pumps
Antisecretory Therapy: PPI
Do not use per tube40mg PO BID20mg PO qdayRabeprazole
See Omeprazole administration60mg PO BID30mg PO qdayLansoprazole
Do not use per tube40mg IV bolus, then 8mg/hr 40mgPO/IV QD-BIDPantoprazole
1) Empty pellets into 40mL of an acidic beverage (fruit juice) - NOT plain water -and administer immediately2) Empty pellets into 10mL of 8.4% sodium bicarbonate - NOT plain water – and allow suspension to form (~15 minutes) or crush. Refrigerate and administer within 14 days
40mg PO BID40mg PO QDOmeprazole
Administration per tubeTreatmentProphylaxisAgent
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Antisecretory Therapy: PPI
AdvantagesIV and enteral administrationAllows quantitative assessment of efficacy via measurement of gastric pHMost rapid and potent suppressor of gastric acid (vs. H2-antagonists and antacids)Numerous clinical studies have shown:
• pH > 4 is achieved more quickly; ↑ duration of time with pH > 4 • Few adverse effects
DisadvantagesInactive until they reach the low pH of the vesicular compartments of parietal cells Drug interactions?Inhibitors of CYP450 2C19
• May interact with SSRIs, warfarin, phenytoin, amiodarone, etc.
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