Dr Jigeeshu Divatia

Health and Me

Sepsis Is Not One Disease: Why Identifying Different Types of Sepsis Could Change Treatment

Sepsis can involve different biological responses, and recognising these subtypes may help doctors better tailor treatment and identify patients at higher risk of complications.

<a href="https://www.healthandme.com/health/sepsis">Sepsis</a> is defined as an organ dysfunction due to a dysregulated host response to infection. In other words, sepsis occurs when the body’s response to an infection injures its own tissues and organs. This may lead to low blood pressure (septic shock), multi-organ failure, and in severe cases death – especially if not recognized early and treated promptly.

Sepsis can develop as a complication of many infectious diseases, including bacterial infections such as pneumonia, urinary tract infections, intra-abdominal infections, etc., as well as viral infections such as dengue, influenza A, H1N1, COVID-19, etc., it can also occur in patients with malaria, and fungal infections. In some cases, organ failure can continue even after the infection has been treated with antibiotics, as the body's altered immune response causes organ damage.

In the past, it was believed that a hyperactive <a href="https://www.healthandme.com/health-news/life-saving-marthas-rule-to-expand-to-emergency-departments-across-england-what-it-means-article-156203375" data-type="tilCustomLink">immune system</a> was primarily responsible for this damage. We now understand that the immune function may be either exaggerated or even suppressed. In a patient with a prolonged illness, immune function may fluctuate between hyperactive and hyporeactive state. Thus, sepsis is no longer considered a homogeneous disease. It varies with the cause, severity of the illness immune response and patient’s response to treatment. At the same time, advances in molecular diagnostics are helping doctors identify the infecting organism and antibiotic resistance mechanisms much earlier than conventional techniques, enabling early and accurate antimicrobial therapy.

Doctors diagnose sepsis when there is confirmed or even suspected infection along with organ dysfunction. While the diagnosis of sepsis itself is a red flag, danger signs include low blood pressure and increasing levels of lactate in the blood. Essential initial treatment consists of early diagnosis and identification of the offending agent, rapid administration of antibiotics, intravenous fluids, and vasopressors to maintain <a href="https://www.healthandme.com/health-wellness/how-to-tell-if-your-low-blood-pressure-is-dangerously-low-all-on-living-with-hypotension-article-151101366" data-type="tilCustomLink">blood pressure</a>. Some patients may also require surgery or other procedures to remove a source of infection in the body.

Advances in biology and artificial intelligence have made it possible to identify patient characteristics or phenotypes, characterize the immune response, and target specific biological and immunological targets. For example, one landmark study found four phenotypes of sepsis (JAMA. 2019 May 28;321(20):2003-2017. doi: 10.1001/jama.2019.5791): 

<ul><li>α (alpha) phenotype was associated with fewer abnormal laboratory values and less organ dysfunction</li><li>β (beta) phenotype, where patients were older, had more chronic illnesses and frequently presented with kidney dysfunction</li><li>γ (gamma) phenotype was characterized by patients with lower albumin levels, higher temperatures, and elevated clinical markers of inflammation</li><li>δ (delta) phenotype was associated with elevated lactate levels and low blood pressure </li></ul>

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Another study classified sepsis patients into SRS1 which was relatively immunosuppressed and SRS2 which was relatively immunocompetent subtypes. Interestingly SRS2 patients had a relatively worse outcome when treated with corticosteroids. (Lancet Respir Med. 2016 Apr;4(4):259-71. doi: 10.1016/S2213-2600(16)00046-1)

While these are exciting developments, some more information and evidence is required before they become the standard of care for sepsis. Doctors are now looking forward to treating sepsis patients on a more personalized basis through precision targeting of immunological pathways to reduce sepsis mortality. 

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Sepsis is defined as an organ dysfunction due to a dysregulated host response to infection. In other words, sepsis occurs when the body’s response to an infection injures its own tissues and organs. This may lead to low blood pressure (septic shock), multi-organ failure, and in severe cases death – especially if not recognized early and treated promptly. Sepsis can develop as a complication of many infectious diseases, including bacterial infections such as pneumonia, urinary tract infections, intra-abdominal infections, etc., as well as viral infections such as dengue, influenza A, H1N1, COVID-19, etc., it can also occur in patients with malaria, and fungal infections. In some cases, organ failure can continue even after the infection has been treated with antibiotics, as the body's altered immune response causes organ damage.What Causes Sepsis?  In the past, it was believed that a hyperactive immune system was primarily responsible for this damage. We now understand that the immune function may be either exaggerated or even suppressed. In a patient with a prolonged illness, immune function may fluctuate between hyperactive and hyporeactive state. Thus, sepsis is no longer considered a homogeneous disease. It varies with the cause, severity of the illness immune response and patient’s response to treatment. At the same time, advances in molecular diagnostics are helping doctors identify the infecting organism and antibiotic resistance mechanisms much earlier than conventional techniques, enabling early and accurate antimicrobial therapy. Doctors diagnose sepsis when there is confirmed or even suspected infection along with organ dysfunction. While the diagnosis of sepsis itself is a red flag, danger signs include low blood pressure and increasing levels of lactate in the blood. Essential initial treatment consists of early diagnosis and identification of the offending agent, rapid administration of antibiotics, intravenous fluids, and vasopressors to maintain blood pressure. Some patients may also require surgery or other procedures to remove a source of infection in the body. Advances in biology and artificial intelligence have made it possible to identify patient characteristics or phenotypes, characterize the immune response, and target specific biological and immunological targets. For example, one landmark study found four phenotypes of sepsis (JAMA. 2019 May 28;321(20):2003-2017. doi: 10.1001/jama.2019.5791): α (alpha) phenotype was associated with fewer abnormal laboratory values and less organ dysfunctionβ (beta) phenotype, where patients were older, had more chronic illnesses and frequently presented with kidney dysfunctionγ (gamma) phenotype was characterized by patients with lower albumin levels, higher temperatures, and elevated clinical markers of inflammationδ (delta) phenotype was associated with elevated lactate levels and low blood pressure          Another study classified sepsis patients into SRS1 which was relatively immunosuppressed and SRS2 which was relatively immunocompetent subtypes. Interestingly SRS2 patients had a relatively worse outcome when treated with corticosteroids. (Lancet Respir Med. 2016 Apr;4(4):259-71. doi: 10.1016/S2213-2600(16)00046-1) While these are exciting developments, some more information and evidence is required before they become the standard of care for sepsis. Doctors are now looking forward to treating sepsis patients on a more personalized basis through precision targeting of immunological pathways to reduce sepsis mortality. 