Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery

Starlinger, Patrick; Pereyra, David; Hackl, Hubert; Ortmayr, Gregor; Braunwarth, Eva; Santol, Jonas; Najarnia, S.; Driedger, Michael; Gregory, Lindsey; Alva-Ruiz, Roberto; Glasgow, Amy E.; Assinger, Alice; Nagorney, David M.; Habermann, Elizabeth B.; Staetttner, Stefan; Cleary, Sean P.; Smoot, Rory L.; Gruenberger, Thomas

doi:10.1002/hep.31601

Cited by 15 publications

(9 citation statements)

References 29 publications

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“…Increasing evidence suggests that platelets are important mediators in HCC carcinogenesis [ 26 , 29 , 30 , 31 ]. In fact, inhibition of platelet function has been correlated with reduced risks of HCC in both animal models [ 32 ] and patients with cirrhosis [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Zanetto

Senzolo

Campello

et al. 2021

Cancers

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Hyper-functional platelets are being proposed as a potential therapeutic target in multiple cancers. Whether this can be considered in patients with cirrhosis and hepatocellular carcinoma (HCC) is unknown as their platelet function has not yet been investigated. We evaluated platelet function in cirrhosis patients with HCC. Patients with cirrhosis with and without HCC were prospectively recruited. Platelet aggregation, a marker of platelet function, was assessed by impedance aggregometry with adenosine diphosphate (ADP), arachidonic acid (ASPI), and thrombin (TRAP) stimulation. Plasmatic levels of Von Willebrand factor antigen (VWF) were also determined. One-hundred patients were recruited (50 cirrhotics with and 50 without HCC). Cirrhosis severity by Child class and platelet count were comparable between cirrhotics with and without HCC. Cirrhotics with HCC had higher ADP- (45 vs. 28; p < 0.001), ASPI- (47 vs. 28; p < 0.001), and TRAP- (85 vs. 75; p = 0.01) induced platelet aggregation than cirrhotics without HCC, all indicative of platelet hyper-function. The relatively increased platelet aggregation in patients with HCC was confirmed after adjusting the analysis for platelet count/severity of thrombocytopenia. Levels of VWF were higher in patients with vs. without HCC (348 vs. 267; p = 0.006), particularly in compensated cirrhosis. In patients with cirrhosis, HCC is associated with increased platelet aggregation and higher VWF. The clinical implications of these findings deserve further investigation.

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Section: Discussionmentioning

confidence: 99%

Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Zanetto

Senzolo

Campello

et al. 2021

Cancers

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“…In contrast, Mawardi et al found that SNRI use independently increases risk of gastrointestinal bleeding in LVAD patients [65]. Recent research also suggests that SSRIs/SNRIs may be associated with poor postoperative outcomes following hepatic resection, and should be held in the perioperative period [66].…”

Section: Intraoperative Considerationsmentioning

confidence: 98%

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations

Fanelli

Weller

Liu

2021

Neurology International

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Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic neuronal uptake of serotonin and norepinephrine and prolong the effects of the monoamines in the synaptic cleft within the central nervous system, leading to increased postsynaptic receptor activation and neuronal activities. Serotonin-norepinephrine reuptake inhibitors can have multiple clinical indications, including as the first-line agents for the management of depression and anxiety, and as analgesics in the treatment of chronic pain. The effects of reuptake inhibition of norepinephrine and serotonin are often dose-dependent and agent-dependent. There are five FDA-approved serotonin-norepinephrine reuptake inhibitors (desvenlafaxine, duloxetine, levomilnacipran, milnacipran and sibutramine) currently being marketed in the United States. As the COVID-19 pandemic significantly increased the incidence and prevalence of anxiety and depression across the country, there are significantly increased prescriptions of these medications perioperatively. Thus, anesthesiologists are more likely than ever to have patients administered with these agents and scheduled for elective or emergency surgical procedures. A thorough understanding of these commonly prescribed serotonin-norepinephrine reuptake inhibitors and their interactions with commonly utilized anesthetic agents is paramount. There are two potentially increased risks related to the continuation of SNRIs through the perioperative period: intraoperative bleeding and serotonin syndrome. SNRIs have some off-label uses, more new indications, and ever-increasing new applications in perioperative practice. This article aims to review the commonly prescribed serotonin-norepinephrine reuptake inhibitors and the current clinical evidence regarding their considerations in perioperative anesthesia and analgesia.

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“…Platelet-derived 5-HT is an important mediator of liver regeneration, most likely through production of growth factors at the site of injury ( 160 , 161 ). Recently a multi-center trial has demonstrated that perioperative use of selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors is associated with adverse outcomes after hepatic resection further supporting a role for 5-HT ( 162 ).…”

Section: The Role Of Platelets In Resolution Of Inflammationmentioning

confidence: 99%

The role of platelet mediated thromboinflammation in acute liver injury

Morris

Chauhan

2022

Front. Immunol.

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Acute liver injuries have wide and varied etiologies and they occur both in patients with and without pre-existent chronic liver disease. Whilst the pathophysiological mechanisms remain distinct, both acute and acute-on-chronic liver injury is typified by deranged serum transaminase levels and if severe or persistent can result in liver failure manifest by a combination of jaundice, coagulopathy and encephalopathy. It is well established that platelets exhibit diverse functions as immune cells and are active participants in inflammation through processes including immunothrombosis or thromboinflammation. Growing evidence suggests platelets play a dualistic role in liver inflammation, shaping the immune response through direct interactions and release of soluble mediators modulating function of liver sinusoidal endothelial cells, stromal cells as well as migrating and tissue-resident leucocytes. Elucidating the pathways involved in initiation, propagation and resolution of the immune response are of interest to identify therapeutic targets. In this review the provocative role of platelets is outlined, highlighting beneficial and detrimental effects in a spatial, temporal and disease-specific manner.

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Consequences of Perioperative Serotonin Reuptake Inhibitor Treatment During Hepatic Surgery

Abstract: This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as

Cited by 15 publications

References 29 publications

Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

Influence of Hepatocellular Carcinoma on Platelet Aggregation in Cirrhosis

New Serotonin-Norepinephrine Reuptake Inhibitors and Their Anesthetic and Analgesic Considerations

The role of platelet mediated thromboinflammation in acute liver injury

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