Multimodal Analgesia's Impact on Opioid Use and Adverse Drug Effects in a Multihospital Health System.

In addition to opioid abuse and dependency, opioid use can lead to opioid related adverse drug events (ORADEs). ORADEs are associated with increased length of stay, cost of care, 30-day readmission rate, and inpatient mortality. The addition of scheduled non-opioid analgesic medications has shown to be effective in reducing opioid utilization in post-surgical and trauma populations, but evidence in entire hospital patient populations is limited.

Sublethal hemorrhage induces tolerance in animals exposed to cecal ligation and puncture by altering p38, p44/42, and SAPK/JNK MAP kinase activation.

Background: We have shown that SLH induces tolerance to endotoxin in vivo and in vitro, and is associated with alterations in MAP kinase (p38, p44/42, and SAPK/JNK) activation and TNF production. This study investigates the effect of sublethal hemorrhage (SLH) on cecal ligation and puncture (CLP) polymicrobial sepsis and examined the effect of the bioflavinoid, curcumin, a MAP kinase inhibitor, on this relationship.

Materials And Methods: Sprague-Dawley rats underwent SLH (hemorrhage and MAP = 30 mm Hg for 15 min, with shed blood returned) or sham operation.

Liver injury during acute pancreatitis: the role of pancreatitis-associated ascitic fluid (PAAF), p38-MAPK, and caspase-3 in inducing hepatocyte apoptosis.

We have demonstrated that pancreatitis-associated ascitic fluid contributes to hepatocyte injury during acute pancreatitis; a phenomenon independent of ascites' enzymatic content and Kupffer cell-derived cytokines. Our aim is to characterize the mechanisms of pancreatitis-associated ascitic fluid induced hepatocyte death. NIH mice were injected intraperitoneally with pathogen-free pancreatitis-associated ascitic fluid.

Regulation of Kupffer cell TNF gene expression during experimental acute pancreatitis: the role of p38-MAPK, ERK1/2, SAPK/JNK, and NF-kappaB.

We have demonstrated that Kupffer cell-derived tumor necrosis factor (TNF) mediates pancreatitis-associated liver injury. The aim of this study was to determine the role of p38 mitogen-activated protein kinase (MAPK), extracellular stress-related kinase 1/2 (ERK1/2), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK), and nuclear factor-kappaB (NF-kappaB) in TNF gene expression within Kupffer cells. TNF and TNF-mRNA were measured in rat livers perfused with elastase.

Pancreatitis-associated ascitic fluid induces hepatocyte death independent of local cytokines.

Introduction: Kupffer-cell-derived cytokines mediate liver injury, yet macrophage pacification does not abolish hepatocyte injury. We undertook this study to examine the role of pancreatitis-associated ascitic fluid (PAAF) in liver injury.

Methods: Pathogen-free PAAF was perfused into healthy rat livers in situ for 60 min (n = 5, sham = 5, LPS = 5).

Effects of tolerizing sublethal hemorrhage on p44/42 and SAPK/JNK Map-kinase activation.

Exposure to sublethal hemorrhage (SLH) makes rats tolerant to subsequent hemorrhagic or septic shock. We have shown that this tolerance leads to alterations in cytokine production, macrophage NF-kappaB activation and p38 MAP-kinase activity. The purpose of this study was to explore whether changes in p44/42 and SAPK/JNK MAP kinase activity also occur after the induction of tolerance by SLH.

Pancreatic elastase induces liver injury by activating cytokine production within Kupffer cells via nuclear factor-Kappa B.

Liver injury is a manifestation of the systemic inflammatory response during acute pancreatitis. We have demonstrated that elastase induces macrophage tumor necrosis factor (TNF) production in distant organs, thus mimicking pancreatitis-associated organ injury. The aim of this study was to determine the mechanism by which elastase induces hepatic cytokine production.