Management of Massive Upper GI Management of Massive Upper GI HaemorrhageHaemorrhage

-Latest Evidence--Latest Evidence-

Management of Massive Upper GI Management of Massive Upper GI HaemorrhageHaemorrhage

-Latest Evidence--Latest Evidence-

Ian Muir - CME

CaseCase

• 52yo female with massive haematemesis• Known alcoholic with cirrhosis (Child B)• Hypotensive and tachycardic, drowsy• Initial actions?

Massive UGIBMassive UGIB• Coordination multiple consultants

-Gastroenterology-Interventional Radiology-General surgery

• Haemodynamically unstable pt in haemorrhagic shock – Haematemesis or Haematochezia

• Majority (>75%) of massive GI bleed is from the upper GI tract (Proximal to ligament of Treitz – D4)

• More common in males and in the elderly (>60)- antiplatelet use/anticoagulants/co-morbidities

• Incidence 1/1000• Mortality 5-10%

• Coordination multiple consultants-Gastroenterology-Interventional Radiology-General surgery

• Haemodynamically unstable pt in haemorrhagic shock – Haematemesis or Haematochezia

• Majority (>75%) of massive GI bleed is from the upper GI tract (Proximal to ligament of Treitz – D4)

• More common in males and in the elderly (>60)- antiplatelet use/anticoagulants/co-morbidities

• Incidence 1/1000• Mortality 5-10%

EtiologyEtiologyPeptic ulcer disease -50%H.pylori,NSAIDS,smokers,ETOH,steroids• Duodenal ulcers – 28%• Gastric Ulcers – 26%• Gastritis – 13%Esophageal/Gastric Varices – 12%-25% (ETOH/Hepatic)• Esophagitis - 8%• Mallory-Weiss – cardio-esophageal tear• Angiodysplasia/Dieulafoy lesions• Boerhaave’s syndrome• Other : Stress ulcers/AVM/Malignancy/Aortoenteric fistula• Exclusion of other sources –pulm/ENT causes - Hemoptysis• 10% no source found

Peptic ulcer disease -50%H.pylori,NSAIDS,smokers,ETOH,steroids• Duodenal ulcers – 28%• Gastric Ulcers – 26%• Gastritis – 13%Esophageal/Gastric Varices – 12%-25% (ETOH/Hepatic)• Esophagitis - 8%• Mallory-Weiss – cardio-esophageal tear• Angiodysplasia/Dieulafoy lesions• Boerhaave’s syndrome• Other : Stress ulcers/AVM/Malignancy/Aortoenteric fistula• Exclusion of other sources –pulm/ENT causes - Hemoptysis• 10% no source found

Management- ResuscitationManagement- Resuscitation• Supplemental O2/Keep NBM 24h• Concurrent assessment and resuscitation• Stabilization and monitoring

A,B-Almost always need endotracheal intubation -Ongoing haematemesis and altered resp.and mental changes -Definitive airway Mx -Facilitation endoscopy -Airway control/protection – Aspiration/ACS -Technically challenging – poor visualization additional personnel and airway adjuncts/TrendellenbergC-2 Large bore peripheral IV cannula’s (16G or larger)-Introducer sized central venous catheter (IJV)/PAWC-Level 1 rapid infusor primed if required-Invasive arterial blood pressure monitor-Comprehensive cardiopulmonary monitoring-Keep warm – Warm fluids and blankets – avoid hypothermia/hypoglycaemia

• Early mobilization of Specialists • Timely transfer to a facility with required skills

• Supplemental O2/Keep NBM 24h• Concurrent assessment and resuscitation• Stabilization and monitoring

A,B-Almost always need endotracheal intubation -Ongoing haematemesis and altered resp.and mental changes -Definitive airway Mx -Facilitation endoscopy -Airway control/protection – Aspiration/ACS -Technically challenging – poor visualization additional personnel and airway adjuncts/TrendellenbergC-2 Large bore peripheral IV cannula’s (16G or larger)-Introducer sized central venous catheter (IJV)/PAWC-Level 1 rapid infusor primed if required-Invasive arterial blood pressure monitor-Comprehensive cardiopulmonary monitoring-Keep warm – Warm fluids and blankets – avoid hypothermia/hypoglycaemia

• Early mobilization of Specialists • Timely transfer to a facility with required skills

Management-ResuscitationManagement-Resuscitation• Medical therapy alone unlikely to achieve haemostasis• NGT and gastric lavage not useful in risk stratification potentially

harmful, may play role in improving visualisation for endoscopy• Consideration of additional monitoring of fluid status- dynamic

measurements –bedside USS –IVC diameter• 1.Repletion of intravascular volume

-Prompt volume resuscitation IV crystalloids – 20ml/kg-500ml aliquots q30mins titrated to parameters-Aim to achieve a perfusing MAP until emergency blood avail.-Lacks O2 carrying capacity-No replenishment of coagulation factors-Hemostatic resuscitation-Avoid excessive fluid resuscitation in cirrhotic pt

• Medical therapy alone unlikely to achieve haemostasis• NGT and gastric lavage not useful in risk stratification potentially

harmful, may play role in improving visualisation for endoscopy• Consideration of additional monitoring of fluid status- dynamic

measurements –bedside USS –IVC diameter• 1.Repletion of intravascular volume

-Prompt volume resuscitation IV crystalloids – 20ml/kg-500ml aliquots q30mins titrated to parameters-Aim to achieve a perfusing MAP until emergency blood avail.-Lacks O2 carrying capacity-No replenishment of coagulation factors-Hemostatic resuscitation-Avoid excessive fluid resuscitation in cirrhotic pt

InvestigationsInvestigations• Bedside : ECG, BSL, VBG, bedside USS• Initial Laboratory tests

- FBE with differential, platelet count, Hct-Group and cross match-U&E ; urea and creatinine ratio -30:1-TEG –Thromboelastography test –evaluate plt fx and Coagulation may direct type of transfusion products required-LFT-Cardiac enzymes –Trop T/I – elderly pt to exclude AMI in large bleed-Coags – INR:>1.8/PT/PTT:>60sec and fibrinogen, D-dimer -FFP,cryoprecipitate and factor concentrate influence results

• Imaging - CXR

• Bedside : ECG, BSL, VBG, bedside USS• Initial Laboratory tests

- FBE with differential, platelet count, Hct-Group and cross match-U&E ; urea and creatinine ratio -30:1-TEG –Thromboelastography test –evaluate plt fx and Coagulation may direct type of transfusion products required-LFT-Cardiac enzymes –Trop T/I – elderly pt to exclude AMI in large bleed-Coags – INR:>1.8/PT/PTT:>60sec and fibrinogen, D-dimer -FFP,cryoprecipitate and factor concentrate influence results

• Imaging - CXR

Management-ResuscitationManagement-Resuscitation• 2.Blood Product Transfusion

-Evidence of volume depletion and continued bleeding- O-neg PRBCs, (O-pos men/females >childbearing)/Crossmatched asap-Intravascular Volume Resuscitation (MAP>60) when Hct <30%-Optimization of O2 carrying capacity -Clinical evidence of decreased O2 delivery – GCS, end-organ hypoperfusion –ishaemia, increase s-lactate, decrease ScvO2 -Hb =<7g/dL or shock – PRBCs, FFP, platelets (1:1:1) – Military Lit.(Iraq) -Restrictive transfusion associated with lower mortality -Hb ideally > 9-10g/dL for unstable CAD/ Elderly -Activation massive transfusion protocol -Monitor complications massive transfusion Ca, Mg – chelation via Na citrate immediate transfusion reactions – Hemolytic/ABO -Avoid hypothermia, acidosis and coagulopathy -Avoid overtransfusion in variceal bleeding (>10g/dL) – increase portal pressure may ppt worsening of bleeding (cirrhotic pt) even with IHD -Rate determined by severity of hypovolaemia,tempo bleeding,and co- morbidities

• 2.Blood Product Transfusion-Evidence of volume depletion and continued bleeding- O-neg PRBCs, (O-pos men/females >childbearing)/Crossmatched asap-Intravascular Volume Resuscitation (MAP>60) when Hct <30%-Optimization of O2 carrying capacity -Clinical evidence of decreased O2 delivery – GCS, end-organ hypoperfusion –ishaemia, increase s-lactate, decrease ScvO2 -Hb =<7g/dL or shock – PRBCs, FFP, platelets (1:1:1) – Military Lit.(Iraq) -Restrictive transfusion associated with lower mortality -Hb ideally > 9-10g/dL for unstable CAD/ Elderly -Activation massive transfusion protocol -Monitor complications massive transfusion Ca, Mg – chelation via Na citrate immediate transfusion reactions – Hemolytic/ABO -Avoid hypothermia, acidosis and coagulopathy -Avoid overtransfusion in variceal bleeding (>10g/dL) – increase portal pressure may ppt worsening of bleeding (cirrhotic pt) even with IHD -Rate determined by severity of hypovolaemia,tempo bleeding,and co- morbidities

Management -SpecificManagement -Specific• Reversal of Coagulopathy

-INR>1.5 and platelets <50000 +/- bleeding – FFP(10ml/kg)/platelets Attempt to get INR <3 prior to endoscopy,should not delay endoscopy -Reversal of medical induced coagulopathy: -Warfarin – 1st Prothrombin complex concentrates (Prothrombinex-VF) -25-50 IU/kg No crossmatch required/acts >rapid than FFP alone - Discontinue Warfarin +Vit. K 5-10mg IV - rFVIIa – expensive/thromboembolism risk conflicting evidence in literature – routine use not recomm. But consider in severe liver disease/refractory bleeding despite FFP -Dabigatran(Pradaxa) –direct thrombin inhibitor – degree of coagulopathy obtain PT and thrombin time –only qaulitative indication, lacks sensitivity with therapeutic dabigatran levels –no evidence, aggressive FFP,rFVIIa, CVVHDF

• Reversal of Coagulopathy -INR>1.5 and platelets <50000 +/- bleeding – FFP(10ml/kg)/platelets Attempt to get INR <3 prior to endoscopy,should not delay endoscopy -Reversal of medical induced coagulopathy: -Warfarin – 1st Prothrombin complex concentrates (Prothrombinex-VF) -25-50 IU/kg No crossmatch required/acts >rapid than FFP alone - Discontinue Warfarin +Vit. K 5-10mg IV - rFVIIa – expensive/thromboembolism risk conflicting evidence in literature – routine use not recomm. But consider in severe liver disease/refractory bleeding despite FFP -Dabigatran(Pradaxa) –direct thrombin inhibitor – degree of coagulopathy obtain PT and thrombin time –only qaulitative indication, lacks sensitivity with therapeutic dabigatran levels –no evidence, aggressive FFP,rFVIIa, CVVHDF

Management -SpecificManagement -Specific• Rivaroxaban(Xarelto) – Xa inhibitor

- PCCs or FFP -UFH – Acts on multiple sites clotting cascade/catalyst clotting factors –Protamine sulphate –basic prot that combines with heparin to form stable inactive complex - 1mg neutralise 100IU Heparin

-Aspirin/Clopidogrel –platelets –no evidence at this stage -Stop NSAIDS

• Weigh thrombotic risk vs continued bleeding and when to resume medications after haemostasis achieved (Cardiology consult if high risk for IHD/Vascular stent)

• Rivaroxaban(Xarelto) – Xa inhibitor - PCCs or FFP -UFH – Acts on multiple sites clotting cascade/catalyst clotting factors –Protamine sulphate –basic prot that combines with heparin to form stable inactive complex - 1mg neutralise 100IU Heparin

-Aspirin/Clopidogrel –platelets –no evidence at this stage -Stop NSAIDS

• Weigh thrombotic risk vs continued bleeding and when to resume medications after haemostasis achieved (Cardiology consult if high risk for IHD/Vascular stent)

Management-SpecificManagement-Specific• Pharmacologic Therapies

-Proton Pump Inhibitors – Inhibition gastric H+/K+ATPase /neutralization of gastric acid/Pepsin Stabilization blood clot-Current emperic in acute UGIB Has been the mainstay early treatment/Adjunct to endoscopy Proposed reduction haemorrhage during endoscopy,no immediate impact No statistical evidence of reduction in rebleeding or the need for surgery or mortality reduction- No benefit 100%-Generally in non variceal bleeding-Cost effective/Excellent safety profile – risk benefit ratio greater in high risk pt’s – 0% harm-Pantoprazole 8mg /infusion 8mg/hr-Concern about the addition of PPI to longterm clopidogrel for risk of thrombotic stroke or AMI – 50% increase with concurrent use over longterm

• Pharmacologic Therapies-Proton Pump Inhibitors – Inhibition gastric H+/K+ATPase /neutralization of gastric acid/Pepsin Stabilization blood clot-Current emperic in acute UGIB Has been the mainstay early treatment/Adjunct to endoscopy Proposed reduction haemorrhage during endoscopy,no immediate impact No statistical evidence of reduction in rebleeding or the need for surgery or mortality reduction- No benefit 100%-Generally in non variceal bleeding-Cost effective/Excellent safety profile – risk benefit ratio greater in high risk pt’s – 0% harm-Pantoprazole 8mg /infusion 8mg/hr-Concern about the addition of PPI to longterm clopidogrel for risk of thrombotic stroke or AMI – 50% increase with concurrent use over longterm

Management-SpecificManagement-Specific• -Somatostatin/Octreotide/Vapreotide (analogues)

-Use is controversial/Inferior to endoscopy -Suspected acute variceal bleeding,not routine for ulcerative bleed -Endoscopy unavailable or contraindicated or uncontrolled bleeding while waiting for endoscopy -Inhibits release of GI hormones: Gastrin/CCK motilin,secretin – reduction portal venous blood flow secondary to splanchnic vasoconstriction -In combination with Endoscopic sclerotherapy -Low risk side effect profile - Potentially reduce risk bleeding non variceal causes(Kim et al) where endoscopy unavailable but not routine or as adjunctive therapy to stabilize pt prior to definitive care Little data exists in non variceal bleeds -Cochrane review –no significant change in mortality or rebleeding but reduce need for blood transfusion by 0.5 units-IV bolus 25-50mcg then 20-50mcg/hr minimum of 24 hours in ICU

• -Somatostatin/Octreotide/Vapreotide (analogues) -Use is controversial/Inferior to endoscopy -Suspected acute variceal bleeding,not routine for ulcerative bleed -Endoscopy unavailable or contraindicated or uncontrolled bleeding while waiting for endoscopy -Inhibits release of GI hormones: Gastrin/CCK motilin,secretin – reduction portal venous blood flow secondary to splanchnic vasoconstriction -In combination with Endoscopic sclerotherapy -Low risk side effect profile - Potentially reduce risk bleeding non variceal causes(Kim et al) where endoscopy unavailable but not routine or as adjunctive therapy to stabilize pt prior to definitive care Little data exists in non variceal bleeds -Cochrane review –no significant change in mortality or rebleeding but reduce need for blood transfusion by 0.5 units-IV bolus 25-50mcg then 20-50mcg/hr minimum of 24 hours in ICU

Management-SpecificManagement-Specific• Vasopressin/Terlipressin

-Reduction of portal HTN via splanchnic and systemic vasoconstriction -Use is controversial/Mortality benefit in Child-Pugh C patients shown with Terlipressin-High rates of serious complications vasopressin (3% fatal)-Risk similar but less severe than other vasopressor therapy(AMI/Arrhythmias/skin necrosis/mesen- teric ischaemia, cardiac arrest, systemic HTN)-Addition of nitroglycerin may decrease side effects but does not affect the efficacy if vasopressin-Use may be justified in pt in extremis due to massive UGIB and exsanguination to achieve hemostasis-Generally use should be limited –caution in OUD bleed-20units IV over 20 minutes then 0.2-0.4 U/min Vasopressin- 2mg q4hly IV (1mg <40kg) Terlipressin

• Vasopressin/Terlipressin-Reduction of portal HTN via splanchnic and systemic vasoconstriction -Use is controversial/Mortality benefit in Child-Pugh C patients shown with Terlipressin-High rates of serious complications vasopressin (3% fatal)-Risk similar but less severe than other vasopressor therapy(AMI/Arrhythmias/skin necrosis/mesen- teric ischaemia, cardiac arrest, systemic HTN)-Addition of nitroglycerin may decrease side effects but does not affect the efficacy if vasopressin-Use may be justified in pt in extremis due to massive UGIB and exsanguination to achieve hemostasis-Generally use should be limited –caution in OUD bleed-20units IV over 20 minutes then 0.2-0.4 U/min Vasopressin- 2mg q4hly IV (1mg <40kg) Terlipressin

Management-SpecificManagement-Specific• Prophylactic Antibiotics

-Patients with Cirrhosis – Bacterial inf.-20% GI bleed -Immune dysfunction -Translocation gut bact - 50% develop HA infection - Increased mortality-May reduce risk of recurrence bleeding in variceal bleeding/Prior or after endoscopy – 23% infection prevention 4.7% prevention death-Cipro 400mg bid/Ceftriaxone 1g IV qid

• Tranexamic acid-No beneficial effect above standard therapy,no role in the treatment of acute UGIB

• H2 antagonists no benefit in acute upper GI bleedno reduction in rebleeding

• Prophylactic Antibiotics -Patients with Cirrhosis – Bacterial inf.-20% GI bleed -Immune dysfunction -Translocation gut bact - 50% develop HA infection - Increased mortality-May reduce risk of recurrence bleeding in variceal bleeding/Prior or after endoscopy – 23% infection prevention 4.7% prevention death-Cipro 400mg bid/Ceftriaxone 1g IV qid

• Tranexamic acid-No beneficial effect above standard therapy,no role in the treatment of acute UGIB

• H2 antagonists no benefit in acute upper GI bleedno reduction in rebleeding

Management-SpecificManagement-Specific

• Prokinetics-Erythromycin/Metclopramide-Improves gastric visualization during endoscopy-Shorten endoscopy time-Reduce need for second-look endoscopy-Consider in large bleeds with large amount blood in stomach-3mg/kg IV – 30-90 minutes prior to endoscopy-More benefit towards use of erythromycin

• Prokinetics-Erythromycin/Metclopramide-Improves gastric visualization during endoscopy-Shorten endoscopy time-Reduce need for second-look endoscopy-Consider in large bleeds with large amount blood in stomach-3mg/kg IV – 30-90 minutes prior to endoscopy-More benefit towards use of erythromycin

Management-SpecificManagement-Specific• Procedural therapies

- Endoscopy -Diagnostic and therapeutic modality of choice -Accurate at locating bleeding site (78-95%) and predict mortality + risk stratification about rebleeding - Banding,clipping, sclerosant injection +/- Adren. Ethanol and thrombin – combination methods >effective -Co-aptive Rx – heater probe thermo-coagulation -Early endoscopy within 4h advocated -Pt need to be HD stable prior to endoscopy – Hct <30% tolerated and mild to moderate anticoagulation -Riks : Aspiration, GA, perforation, increased bleeding systemic sclerosing agent dissemination -More complications associated with recent AMI and very ill patients – Apache II score >16/hypotension -Forest classification – description of peptic ulcers

• Procedural therapies- Endoscopy -Diagnostic and therapeutic modality of choice -Accurate at locating bleeding site (78-95%) and predict mortality + risk stratification about rebleeding - Banding,clipping, sclerosant injection +/- Adren. Ethanol and thrombin – combination methods >effective -Co-aptive Rx – heater probe thermo-coagulation -Early endoscopy within 4h advocated -Pt need to be HD stable prior to endoscopy – Hct <30% tolerated and mild to moderate anticoagulation -Riks : Aspiration, GA, perforation, increased bleeding systemic sclerosing agent dissemination -More complications associated with recent AMI and very ill patients – Apache II score >16/hypotension -Forest classification – description of peptic ulcers

Management-SpecificManagement-Specific• Balloon tamponade

-Endoscopy not available or ineffective haemostasis despite adequate resuscitation-Requires pt to be intubated-Rare but potentially life saving procedure- 3 lumen/Gastric + esophageal balloon/gastric suc- tion port – nasal/oral @ 50cm–inflate <40-50mmHg- Confirm correct placement prior to inflation-Temporary rescue device – stops bleeding 80%-Associated with high risk re-bleeding on deflation-Lethal complications of esophageal necrosis and rupture (14% major compl/3% fatal),asphyxiation-Senstagen-Blakemore, Minnesota tube,Linton (>effective in Gastric variceal bleeding)-Transfer to facility with definitive care

• Balloon tamponade-Endoscopy not available or ineffective haemostasis despite adequate resuscitation-Requires pt to be intubated-Rare but potentially life saving procedure- 3 lumen/Gastric + esophageal balloon/gastric suc- tion port – nasal/oral @ 50cm–inflate <40-50mmHg- Confirm correct placement prior to inflation-Temporary rescue device – stops bleeding 80%-Associated with high risk re-bleeding on deflation-Lethal complications of esophageal necrosis and rupture (14% major compl/3% fatal),asphyxiation-Senstagen-Blakemore, Minnesota tube,Linton (>effective in Gastric variceal bleeding)-Transfer to facility with definitive care

Management-SpecificManagement-Specific• Additional Procedural Therapies

-Angiography – Nonvariceal/Failed Endoscopy/1% of pt - Failed medical management - Endoscopy unavailable/High risk surgery - Detect bleeds of 0.5ml/min with 100% sens. - Transcatheter embolization Gelfoam/vasopressin -Radionuclide imaging – Localization/identification source indolent/elusive (Nuclear isotope-tagged RBC scan) - Upper GI Barium studies contraindicated - Wireless capsule endoscopy in ED on presentation esophageal capsule- 20minutes recording time - Colonoscopy – negative gastroscopy/hematochezia -Surgery – perforation or peritonism/precipitation massive bleed during endoscopy (>5units first 4-6h) -Aorta-enteric fistula (Aortic stent/graft) -Less effective in variceal bleeding Rx-TIPS Transjugular Intrahepatic Portosystemic Shunt (23% mortality)

• Additional Procedural Therapies -Angiography – Nonvariceal/Failed Endoscopy/1% of pt - Failed medical management - Endoscopy unavailable/High risk surgery - Detect bleeds of 0.5ml/min with 100% sens. - Transcatheter embolization Gelfoam/vasopressin -Radionuclide imaging – Localization/identification source indolent/elusive (Nuclear isotope-tagged RBC scan) - Upper GI Barium studies contraindicated - Wireless capsule endoscopy in ED on presentation esophageal capsule- 20minutes recording time - Colonoscopy – negative gastroscopy/hematochezia -Surgery – perforation or peritonism/precipitation massive bleed during endoscopy (>5units first 4-6h) -Aorta-enteric fistula (Aortic stent/graft) -Less effective in variceal bleeding Rx-TIPS Transjugular Intrahepatic Portosystemic Shunt (23% mortality)

DispositionDisposition• ICU – Hct<30%, syst BP<100, Hx cirrhosis/ascites

vomiting frank red blood• Manage complications associated with alcoholism

and hepatic encephalopathy• Early involvement sub specialities• Interfacility transfer if required• Risk stratification: Rockall/Modified Blatchford

AIMS65 • Long term : Beta blocker therapy in pt with

varices may prevent initial bleed and rebleed H.pylori eradication therapy

• ICU – Hct<30%, syst BP<100, Hx cirrhosis/ascites vomiting frank red blood

• Manage complications associated with alcoholismand hepatic encephalopathy

• Early involvement sub specialities• Interfacility transfer if required• Risk stratification: Rockall/Modified Blatchford

AIMS65 • Long term : Beta blocker therapy in pt with

varices may prevent initial bleed and rebleed H.pylori eradication therapy

Questions?• References

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