The Gut-Lymph Model Gives New Treatment Strategies for Organ Failure

Abstract

Organ Failure Remains an Unmet Global ChallengeEach year, more than 20 million people with organ failure (OF) are admitted to intensive care units around the world. 1 With a 30% mortality rate, it remains the leading cause of death in intensive care units. OF is preceded by 2 syndromes, the systemic inflammatory response (SIRS) and multiple organ dysfunction (MODS), which can progress throughout days or weeks to single or multiple OF and death. 2 This patterned sequence is the feared sequelae of many inciting acute and critical diseases (ACDs), which include severe sepsis, hemorrhage, trauma, burns, acute pancreatitis, and most recently, SARS-CoV-2 infection. 3 The heart, lung, and kidney organ systems are most at risk of failing. The failure to translate multiple putative drug treatments to arrest OF is well documented. 2 Current treatment standards for SIRS/MODS/OF are generic, including fluid resuscitation, inotropes, mechanical ventilation, and kidney replacement therapy. While optimizing physiology is a worthy goal, 3 there is an urgent need for a new paradigm to introduce effective treatment strategies that go beyond organ support to target specific disease mechanisms to mitigate SIRS/ MODS/OF and the risk of death.

Intraluminal oxygen mitigates acute mesenteric ischaemia: a systematic review of methods and outcomes in animal studies

“…When applied in critical illness, intraluminal oxygen therapy could protect the gut from NOMI, where clinicians have little option other than supportive care. Mitigation of gut injury in this setting may limit the generation of toxic mesenteric lymph and offer a novel option for the prevention of multiorgan failure 11 . Other potential clinical settings include the treatment of necrotising enterocolitis, as a bridge to arterial re‐vascularisation and post‐operatively to support intestinal anastomotic healing.…”

“…Mitigation of gut injury in this setting may limit the generation of toxic mesenteric lymph and offer a novel option for the prevention of multiorgan failure. 11 Other potential clinical settings include the treatment of necrotising enterocolitis, as a bridge to arterial re-vascularisation and post-operatively to support intestinal anastomotic healing. Surprisingly, no clinical studies have been published exploring the intraluminal oxygen treatment of AMI.…”

“…Local complications such as intestinal infarction require surgical resection, but treatment is often too late to prevent the systemic inflammatory response. Given the central role of intestinal damage in propelling multiorgan failure, treatments that mitigate intestinal ischaemia could significantly improve the care of critically ill patients 11 …”

“…Given the central role of intestinal damage in propelling multiorgan failure, treatments that mitigate intestinal ischaemia could significantly improve the care of critically ill patients. 11 A promising experimental approach to the treatment of AMI is the delivery of oxygen to the intestinal lumen. Intraluminal oxygen treatment has been assessed in the preclinical setting [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] but to our knowledge has not entered clinical practice.…”