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Acute Pharmacologic Agents for Upper GI Bleeds? | Liver Disorders | #CodeBlueDebrief


 


Are you taking up a line with IV pantoprazole? When should blood products have priority for access? What clinical benefits does pantoprazole even provide for acute esophageal varices?


Whatsup guys, Mark with PHARMWYZE. I'm a board-certified emergency medicine pharmacist that makes clinical pharmacotherapy content on the social medias. Thanks for joining me on the Code Blue Debrief: A Clinical Pharmacotherapy YouTube & Podcast series. The focus of our discussion today will be on IV pantoprazole administration strategies and clinical benefits for acute variceal bleeds.


Two high acuity patient populations I had a lot of exposure to as a COVID resident was obviously, the COVIDs, and also cirrhotic patients. Those working in emergency medicine and critical care, you know what I'm talking about during that time. You tend to be biased when you work with critically ill patients since you see the worse of the worst.


Training during a time of severely sick COVID and liver bomb patients was an invaluable experience for my growth. It was a crash course on consistent, solid patient care workup & diverse exposure in critically ill patients.


Cirrhosis is one of my favorite disease states to learn about. It amazes me how much self-induced complications come from alcohol as a legal substance compared to other things considered illegal.


Esophageal varices are one of those complications that develop overtime from increased systemic portal hypertension. They can eventually rupture, leading to hemorrhagic shock in a liver bomb patient with coagulapathy abnormalities. Thats just one of many ongoing problems.


Pharmacologic agents in the acute setting include acid suppression, vasoactive agents, and antibiotics. We'll primarily discuss the clinical benefits of pantoprazole vasoactive and antibiotic for cirrhotic patients. It'll help triage a complex patient with limited access and need for blood transfusion. Theres only two outlets GI bleeds can go out of. Let's talk about how portal hypertension develops from a fatty liver.


Pathophysiology

Most cases of portal hypertension in western countries have underlying cirrhosis. Chronic use of alcohol damages the liver, leading to structural changes from fibrosis and inflammation.


Decreased liver function from cirrhosis increases intrahepatic resistance and splanchnic vasodilation. Hepatic steotosis contributes to alterations in inflammatory mediators, including nitric oxide and VEGF. This results in subsequent increased portal hypertension. Varices develop from this pressure at the esophageal circulation. point.


Eventually, these varcies can rupture from an overpressure leading to an acute esophageal variceal bleed. Hemorrhagic shock would be the primary concern right now in severe cases. Hemorrhagic source control with prompt endoscopy is the solution. Pharmacologic agents are crucial for pre- and post-endoscopy management, in addition to optimizing resuscitation.


Specifically with variceal bleeds, we'll be considering indications for acid suppression, vasoactive agents, and antibiotics.


Acute Management

  • Optimize resuscitation

  • Pre- & post-endoscopic management

  • Timely endoscopic intervention

Endoscopy is crucial for identifying the source of the bleed and establish hemorrhage source control. Optimizing resuscitation includes securing your ABCs, blood transfusions over crystalloids in the setting of hemorrhagic shock, and reversal of anticoagulants, when appropriate.


Acid Suppression

  • Proton pump inhibitors (PPI) suppresses gastric secretion and increase gastric pH

  • Promotes platelet adhesion & minimizes clot dissolution (reduces rebleeding)

  • Historically, continuous IV infusion pantoprazole 80 mg bolus, then 8 mg/hr has been used used but more recent evidence supports use intermittent dosing with 80 mg IV then 40 mg IV every 12 hours.


 

Are you taking up a line with IV pantoprazole? When should blood products have priority for access? What clinical benefits does pantoprazole even provide for acute esophageal varices?


Whatsup guys, Mark with PHARMWYZE. I'm a board-certified emergency medicine pharmacist that makes clinical pharmacotherapy content on the social medias. Thanks for joining me on the Code Blue Debrief: A Clinical Pharmacotherapy YouTube & Podcast series. The focus of our discussion today will be on IV pantoprazole administration strategies and clinical benefits for acute variceal bleeds.


Two high acuity patient populations during COVID I had a lot of exposure to, was obviously the COVIDz, and also cirrhotic patients. Working in emergency medicine and critical care, you know what I'm talking about during that time. You tend to be biased when you work with critically ill patients since you see the worse of the worst.


Training during a time of severely sick COVID and liver bomb patients was an invaluable experience. It was a crash course on good, consistent patient care habits and developing my approach to the problem list.


Cirrhosis is one of my favorite disease states to learn about. It amazes me how much self-induced complications come from alcohol as a legal substance compared to other things considered illegal.


Esophageal varices are one of those complications that develop overtime from increased systemic portal hypertension. They can eventually rupture, leading to hemorrhagic shock in a liver bomb with coagulapathy abnormalities. Thats just one of many ongoing problems.


Pharmacologic agents in the acute setting include acid suppression, vasoactive agents, and antibiotics. We'll primarily discuss pantoprazole dosing strategies and briefly discuss vasoactive and antibiotic benefits for cirrhotic patients. Theres only two outlets GI bleeds can go out of. Let's talk about how portal hypertension develops from a fatty liver.


 

Pathophysiology

Most cases of portal hypertension in western countries have underlying cirrhosis. Chronic use of alcohol damages the liver, leading to structural changes from fibrosis and inflammation. This eventually leads to a cascade of complications from increased portal hypertension, splanchnic vasodilation, and bacterial translocation


Decreased liver function from cirrhosis increases intrahepatic resistance and splanchnic vasodilation. Hepatic steotosis contributes to alterations in inflammatory mediators, including nitric oxide and VEGF. This results in subsequent increased portal hypertension. Varices develop from this pressure at the esophageal circulation point.


These varices can rupture from an overpressure leading to an acute esophageal variceal bleed. Hemorrhagic shock would be the primary concern right now in severe cases. Hemorrhagic source control with prompt endoscopy is the solution. Pharmacologic agents are crucial for pre- and post-endoscopy management, in addition to optimizing resuscitation. Interventions for hemmorhage control from endoscopy exploration include bipolar electrocoagulation, and clipping.


There are several pharmacologic agents to keep in mind specifically for acute esophageal bleeds; proton pump inhibitors, somatostatin analogues, and antibiotics. Patients who are in hemorrhagic shock will need intravenous access for blood transfusion. Blood always takes access priority for these patients. Let's review the clinical benefits of pharmacologic agents, it might help you understand what medications are important.


 

Proton Pump Inhibitors


Proton pump inhibitors (PPI) suppresses gastric secretion and increase gastric pH.

Promotes platelet adhesion & minimizes clot dissolution (reduces rebleeding). The initial load of pantoprazole would theoretically get you above an intragastric pH above 6, which would be the target for proposed benefit. Literature supports use of proton pump inhibitors post-endoscopy with meta-analysis indicating: they reduce blood the incidence of rebleeding, blood transfusion requirements, need for urgent intervention, and additional endoscopy. How about the acute patients we get in the emergency department before endoscopy? What is the importance of acid suppression in this setting?


There has been conflicting evidence on whether acid suppression for UGIB has clinical benefit pre-endoscopy. The American College of Gastroenterology 2021 Upper GI and Ulcer Bleeding Guidelines shifted their stance by indicating, "We could not reach a recommendation for or against pre-endoscopic PPI therapy for patients with UGIB." Literature is insufficient to support routine pre-endoscopic PPI, which is consistent with other global health organizations.


As mentioned earlier, an IV bolus of pantoprazole 80 mg would achieve an intragastric pH greater than 6. Pantoprazole IV is not compatible with many high acuity medications and blood products. Studies comparing intermittent pantoprazole to the historically used continuous infusion indicate that both dosing regimens have similar clinical and safety outcomes.


Sachar and colleagues completed a meta-analysis in 2014 comparing continuous infusion pantoprazole 80 mg IV, then 8 mg/hour to intermittent pantoprazole 80mg IV, then 40 mg every 12 hours. The primary outcome was rebleeding within 7 days, with additional outcomes including rebleeding within 3 and 30 days, need for urgent intervention, mortality, red blood cell transfusion, and length of hospital stay. Intermittent pantoprazole was noninferior to continuous infusion for their outcomes.


The 2021 ACG Guidelines list continuous infusion or intermittent dosing post-endoscopy appropriate for upper GI and ulcer bleeding. Most times you never know when a patient can actually get arranged for a STAT endoscopy while you're in the kitchen sink. I'm not delaying other prioritized therapies for pantoprazole, but if conditions permit, the IV bolus should be sufficient. Octreotide probably comes to mind with upper GI bleeds as well.


Sachar H, Vaidya K, Laine L. JAMA Intern Med . 2014 Nov;174(11):1755-62.


 

Vasoactive agents have been a mainstay of therapy for variceal hemorrhages.

Octreotide, a somatostatin analogue, is the only agent available in the US. The medication reduces portal blood flow and portal pressures. Octreotide has been compared to several other agents and varying outcomes, including vasopressin, terlipressin, sclerotherapy assessing mortality and rebleeding amongst others. The results of these trials show octreotide to be as effective and even more safe than certain treatment regimens previously used.


The 2016 American Association for the Study of Liver Diseases Cirrhosis Management Guidelines indicate that octreotide should be initiated as soon as possible in acute variceal bleeds.


The dosing octreotide 50 - 100 mcg IV bolus, then 50 mcg/hr continuous infusion for two to five days. Additionally, octreotide 100 mcg subcutaneously three times daily has been utilized as well. There isn't high quality evidence that shows a reduction in mortality, but it mechanistically targets the source of our problem and decreases rebleeding. In the really sick, bleeding patient, I'm thinking of octreotide before pantoprazole, but second after prophylactic antibiotics.

 

Patients with decompensated cirrhosis and acute variceal bleeding has shown the most benefit with antibiotic prophylaxis in cirrhosis with several guidelines supporting this practice. Bacterial translocation increases the risk of infection, including spontaneous bacterial peritonitis. Prophylactic antibiotics have been associated with a reduction in overall mortality and incidence of bacterial infections.


Ceftriaxone 1 gm IV qday for 5 - 7 days prophylaxis

Ceftriaxone 2gm IV qday for 5 days treatment


With more proven downstream mortality benefit, antibiotics for decompensated cirrhosis and acute variceal bleeding would be the prioritized agent of these three medications.


 

Just keep to the basics and start, secure, and maintain the ABCs. It is easy to get excited about giving medications, but consider the importance of each agent likely doesn't outweigh prioritization over or delaying blood products. Hemorrhagic shock needs to be resuscitated with blood products. Stay on top of calcium salts during MTP and reverse anticoagulants. As access and conditions permit, I'd work my way through ceftriaxone, pantoprazole, and octreotide. Let me know in the comments below, how important are these pharmacologic agents in decompensated cirrhosis and acute variceal bleeding.


Thanks for joining me on the Code Blue Debrief. Make sure to hit the subscribe, follow, and notification bell. Check out my other pharmacotherapy content on the social medias. Theres been a lot of negative energy around the world lately, sending positive vibes your way and I hope you learned something new.



 

References

Smith A, Baumgartner K, & Bositis C. Cirrhosis: Diagnosis and Management. Am Fam Physician . 2019 Dec 15;100(12):759-770.

Yoshiji et al. Evidence-based clinical practice guidelines for Liver Cirrhosis 2020. J Gastroenterol . 2021 Jul;56(7):593-619.

Laine et al. ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol . 2021 May 1;116(5):899-917.

Garcia-Tsao et al. Portal hypertensive bleeding in cirrhosis: Risk stratification, diagnosis, and management: 2016 practice guidance by the American Association for the study of liver diseases. Hepatology . 2017 Jan;65(1):310-335. doi: 10.1002/hep.28906.

Sachar H, Vaidyta K, Laine L. Intermittent vs continuous proton pump inhibitor therapy for high-risk bleeding ulcers: a systematic review and meta-analysis. JAMA Intern Med . 2014 Nov;174(11):1755-62.

Lau JY, Leung WK, Wu JC, et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007;356:1631–40.

Zia H, Aby E, Rabiee A. An Update on the Management of Esophageal Variceal Hemorrhage. Clin Liver Dis (Hoboken). 2021 Oct; 18(4): 179–183.

Garcia-Tsao G. Overview of Current Management of Portal Hypertension. Gastroenterol Hepatol (N Y) . 2021 Jan;17(1):40-42.

Gao et al. Pharmacological management of portal hypertension: current status and future. Chin Med J (Engl). 2020 Oct 5; 133(19): 2362–2364.

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