What is Systemic Inflammatory Response Syndrome?
Systemic inflammatory response syndrome (SIRS) is the body’s extreme reaction to harmful events such as infection, injury, surgery, inflammation, lack of blood flow or even certain types of cancer. During SIRS, your body releases specific substances known as acute-phase reactants, which affect your nervous system, hormones, blood cells, and immune system. While this reaction is intended to protect your body, an uncontrolled release of these substances can cause severe inflammation and damage to your organs, which can be reversible or even irreversible, and may even lead to death in severe cases.
When SIRS occurs due to an infection, it’s referred to as sepsis. It’s important to note that you can have sepsis even in the early stages of an infection, even if lab tests haven’t confirmed the infection yet. If sepsis leads to the failure of one or more organs, it’s called severe sepsis. And when there’s a drop in blood pressure that can’t be corrected by giving fluids, it’s referred to as septic shock. Essentially, these terms represent a progression or worsening of the body’s responses to harmful stimuli.
Furthermore, the term “multiple organ dysfunction syndrome” (MODS) has been widely acknowledged. This term describes a situation where an infection in a sick patient causes changes in organ function that wouldn’t allow the body to maintain a stable internal environment without medical assistance.
SIRS is diagnosed when at least two of the following symptoms are present:
- Body temperature higher than 100.4 degrees Fahrenheit or lower than 96.8 degrees Fahrenheit.
- Heart rate faster than 90 beats per minute.
- Respiratory rate faster than 20 breaths per minute or low levels of carbon dioxide in your blood.
- White blood cell count higher than 12000 or lower than 4000 or over 10% immature forms.
In children, the diagnosis criteria slightly differ and need to include abnormal white blood cell count or temperature, as changes in heart rate and respiratory rates are more common in this age group.
It’s important to understand that while all septic patients have SIRS, not all SIRS patients are septic. Basically, this means you can have SIRS without having sepsis. There are exceptions to this rule, particularly in elderly patients and young children who may not initially have the symptoms required for a SIRS diagnosis but may still progress to severe infection and organ damage.
Several scoring systems are used to assess the severity of the damage to organs by SIRS or sepsis, including the APACHE II and III, MOD score, SOFA, and LOD scores.
The concepts and definitions of SIRS, sepsis, and other related terms have evolved a great deal over time, and continue to do so. For instance, the role of SIRS in defining sepsis has been somewhat altered in a newer definition, Sepsis-3, proposed by a joint task force in 2016. The new definition casually describes sepsis as a life-threatening organ dysfunction caused by a faulty response of the host to infection, and introduces a simpler, more effective scoring system for organ dysfunction known as q SOFA. This new system considers lower than normal blood pressure, high respiratory rates, and altered mental status for sepsis diagnosis.
The validity of q SOFA is limited in an ICU setting but has consistently proven to be more effective than SIRS in predicting organ dysfunction in a non-ICU and ER settings.
What Causes Systemic Inflammatory Response Syndrome?
Systemic inflammatory response syndrome (SIRS) is the body’s response to an injury or illness. It can occur due to a range of reasons. On a cellular level, there are two primary ways this syndrome can start:
1. Damage Associated Molecular Pattern (DAMP) – The body reacts to injury or harm that’s not caused by infection.
2. Pathogen Associated Molecular Pattern (PAMP) – The body responds to infection.
In everyday speech, there are several common causes for this syndrome:
Digging deeper into DAMP:
* Burns
* Trauma or injuries
* Trauma from a surgical procedure
* Inhaling a foreign substance
* Acute pancreatitis – inflammation of the pancreas, an organ near the stomach
* Substance abuse and related poisonings
* Acute end-organ ischemia – a condition where an organ doesn’t get enough blood
* Acute flare-up of an autoimmune vasculitis – an illness where your immune system attacks your blood vessels
* Adverse reaction to a medication
* Intestinal ischemia and perforation – when the intestine doesn’t get enough blood and gets a hole in it
* Blood diseases linked to cancer
* Erythema multiforme – a type of skin rash
Explaining PAMP further:
* Bacterial infection
* Viral syndrome-like influenza – a group of symptoms that resemble the flu
* Widespread fungal infection in immune-suppressed people – this happens when the immune system isn’t working well
* Toxic shock syndrome derived from both exotoxins and endotoxins – a severe and potentially life-threatening illness caused by toxins (poisons) from bacteria
PAMP can be further categorized based on where the infection is in your body and how far it has spread. This can range from an infection in a specific organ to widespread infection (bacteremia) and sepsis, an extreme response to an infection that can be life-threatening.
Risk Factors and Frequency for Systemic Inflammatory Response Syndrome
Systemic Inflammatory Response Syndrome (SIRS), a medical condition which involves widespread inflammation throughout the body, is often hard to track accurately. Not everyone with SIRS makes it to a hospital or healthcare facility. Many people with acute viral syndromes, a common cause of SIRS, are treated in an urgent care or emergency room setting and then recover at home. Therefore, the true incidence of SIRS is only reflected by patients who become severe enough to be admitted to the hospital, which could make the condition seem more deadly than it really is.
A study by Churpeck and team involving nearly 270,000 hospitalized patients showed that 15% met at least two criteria for SIRS when they were admitted, and a surprising 47% met the criteria at some point during their hospital stay. The mortality rate was much higher, 4.3%, for patients with SIRS compared to 1.2% for those without SIRS.
According to Comstedt and team, 62% of patients arriving at the emergency department with SIRS had a confirmed infection. However, interestingly, 38% of infected patients did not show signs of SIRS. A study of hospital admissions found:
- 68% of patients admitted met SIRS criteria.
- 26% developed sepsis, a serious infection that can lead to organ failure.
- 18% developed severe sepsis, a more serious form of sepsis that can cause shock and multiple organ failure.
- 4% developed septic shock, a life-threatening condition where the body’s response to infection causes dangerously low blood pressure.
Differences also exist based on gender and race. For example, research has shown that estrogen may have a protective effect, leading to fewer cases of SIRS in women and African Americans. However, age and having other medical conditions can negatively affect the outcome of SIRS.
Signs and Symptoms of Systemic Inflammatory Response Syndrome
When someone first starts to feel unwell, the symptoms can be similar no matter what the cause is. Signs can include redness, warmth, pain, swelling, and loss of function. To understand what’s causing these symptoms, doctors will ask questions about the details of the discomfort, such as where it hurts, what the pain feels like, if anything makes it feel worse or better, how long it’s been happening, and when symptoms begin and end. Other key details could include any recent changes in normal habits, like new medications taken, food eaten, places visited, and any substances used recreationally.
When doctors know about certain risk factors, it helps them decide which treatments could work best. These factors could include a weak immune system, diabetes, solid tumors and leukemia, dysproteinemias, liver cirrhosis, and being very young or very old.
A complete physical exam is really precious for doctors. It helps them figure out the source of the discomfort, how much of the body is affected, and if any complications have occurred in affected body parts. This information can also steer towards the right tests and medical images to clarify what’s happening in the body.
Systemic inflammatory response syndrome is a condition defined through vital signs like heart rate, blood pressure, temperature, and white blood cell count. However, these signs can be misinterpreted due to stress, extreme ages, or the use of certain medications like beta-blockers or calcium channel blockers. For this reason, it’s important to consistently monitor these signs to ensure a correct diagnosis.
Testing for Systemic Inflammatory Response Syndrome
In recent years, more emphasis has been placed on using objective measurements to diagnose and manage sepsis, a life-threatening reaction to an infection. It is critical to recognize signs of sepsis early in order to provide better treatment and control.
Pioneering discoveries made at the end of the 20th century shed light on the complexities of sepsis, including its causes and potential treatment targets. As we better understood that sepsis is an escalating series of events, from simple inflammation to severe organ damage, it became clear that early diagnosis could significantly reduce the risks of death and long-term harm associated with the condition.
This knowledge has led to the creation of several scoring systems, such as the APACHE score, SIRS score, and SOFA score, among others. These scoring systems help to identify the presence of sepsis, gauge the risk of organ damage, and predict the chance of in-hospital death.
When investigating the cause of a patient’s sepsis, medical teams focus on potential sources of infection. It is recommended to collect samples from blood, sputum (mucus), urine, and any wounds for testing as soon as possible and before starting antibiotic treatment.
Along with this, doctors continue to monitor the patient’s basic metabolic panel and lactic acid levels to assess organ function and blood flow.
Biomarkers, which are measurable substances in the body that can indicate disease, can also help identify sepsis at an early stage, even before the results of microbial tests are available. Procalcitonin (PCT), a protein found in the blood, is one of these biomarkers. Its levels are usually low in healthy individuals but can increase significantly in response to bacterial, fungal, or parasitic incidents.
Increased lactic acid can, on the other hand, indicate issues with tissue function or problems with liver function leading to lactate clearance. Additionally, proteins like interleukin 6 and leptin, when observed at certain levels, can also indicate a high chance of multi-organ damage and help differentiating between infectious versus non-infectious causes.
Markers in our blood vessels, such as Angiopoietin 1 and 2, soluble E- selectin, and P- selectin levels, can also help differentiate between septic and non-septic causes of SIRS. Moreover, researchers are examining additional potential biomarkers that may distinguish between septic and non-septic causes of sepsis.
The analysis of transcriptomes, or the set of all RNA molecules produced in one population of cells, is yet another promising area of research. This new direction may help to identify patients with sepsis who are at high risk of organ failure and other severe conditions at an early stage.
Treatment Options for Systemic Inflammatory Response Syndrome
Systemic inflammatory response syndrome (SIRS) is a medical condition that occurs because of an underlying issue in the body. The treatment for this syndrome is focused on dealing with the root cause of the problem. The aim of the treatment is to stop the condition from escalating into shock or multiple organ dysfunction (where more than one organ starts failing).
One of the key areas of treatment is ensuring the patient’s body is stable and working sufficiently, especially when dealing with severe types of sepsis (an extreme reaction to an infection). In these instances, doctors tend to start treatment by giving fluids rapidly to increase blood flow. While the amount of fluid given is usually the same for all patients, this can sometimes spark debates among medical professionals because patients’ bodies are different and have different needs. Therefore, the amount of fluids given after the initial treatment can differ based on how the patient’s body is responding.
If the patient’s condition doesn’t improve after giving them fluids, extra treatments such as medicines to constrict blood vessels or increase the heart’s pumping action may be considered. Depending on the underlying cause of SIRS, surgery may also be required, for example, to drain an infection.
When doctors suspect that sepsis is the underlying cause of SIRS, patients are typically given a broad range of antibiotics (that can treat many types of bacterial infections) as soon as possible after taking tests for further investigation. However, the choice of antibiotic can depend on several factors, including whether the patient got the infection in the hospital or out in the community, previous patterns of infections, and common types of bacteria seen in the hospital. Once the test results are ready, doctors adjust the antibiotic therapy accordingly.
In some cases, such as severe respiratory problems during the flu season, antiviral therapy may be required. Moreover, patients with weak immune systems or who are receiving their nutrition intravenously may need antifungal medication if their condition doesn’t improve with antibiotics.
Doctors may also use glucocorticoids, which are steroids that help to control inflammation in the body, in patients whose shock does not get better with fluid therapy. Blood glucose control is also important in the management of SIRS, and doctors recommend maintaining a blood glucose level of less than 180 mg/dL.
What else can Systemic Inflammatory Response Syndrome be?
The Systemic Inflammatory Response Syndrome (SIRS) is a sensitive term that requires meeting only two out of its four criteria. However, this can also lead to its frequent misuse because the two SIRS criteria can be indicative of various conditions in an emergency setting that do not necessarily flag an underlying state of inflammation, which is what SIRS implies. Some of these conditions include:
When an individual exhibits rapid breathing and heart rate (Tachypnea and Tachycardia):
- Acute severe asthma with continuous administration of beta-agonists
- Acute toxicity due to excessive consumption of aspirin
- Acute alcohol poisoning
- Panic attacks
- Acute ketoacidosis, resulting from diabetes, dehydration, or starvation
When an individual exhibits rapid heart rate and high body temperature (Tachycardia with Hyperthermia):
- Thyrotoxic crisis, a severe thyroid condition
- Acute intoxication with substance abuse, such as hallucinogens or mood-enhancing drugs
- Serotonin syndrome, often caused by drug interactions
- Malignant hyperthermia, a reaction to certain medication used in general anesthesia
- Neuroleptic malignant syndrome, a reaction to some psychiatric medications
When an individual exhibits high body temperature and high white blood cell count (Hyperthermia and Leucocytosis):
- Neurogenic emergency like an acute hemorrhagic stroke in the brainstem (pontine)
Periodically reassessing these clinical criteria over time, and cross-checking with lab tests, can help to distinguish these conditions from a genuine inflammatory scenario that would confirm SIRS.
What to expect with Systemic Inflammatory Response Syndrome
If a patient scores 2 or more on the systemic inflammatory response syndrome (SIRS) test on their first day in the hospital, it’s more likely that they will develop multiorgan dysfunction syndrome (a severe condition that affects multiple organs). They may also need to stay longer in the intensive care unit (ICU), may require a breathing machine, and may need medications to control their blood pressure. They might also need blood or blood products.
The time from having a SIRS to developing sepsis (a serious infection that can lead to organ failure) can vary. Generally, the more SIRS criteria a patient meets when they are admitted to the hospital, the quicker they may develop sepsis.
In a study by Rangel-Fausto et al., the death rates were found to be 7% for SIRS, 16% for sepsis, 20% for severe sepsis, and 46% for septic shock (a severe and often fatal condition resulting from sepsis).
However, in a similar study by Shapiro et al., they found the death rates to be 1.3% for sepsis, 9.2% for severe sepsis, and 28% for septic shock. This change in numbers over a decade (first study in 1995 and second study in 2006) reflects improved medical practices, including the use of early, goal-focused therapies and proven ways to lower risk, such as prevention of deep vein thrombosis (DVT, a blood clot that forms in a deep vein), controlling blood sugar, using lung-protective methods in mechanical ventilation, early waking and starting to move as soon as possible.
Interestingly, the second study also found that just having SIRS criteria alone did not correlate with in-hospital or 1-year death rates. Instead, organ dysfunction was found to be a better predictor of death rates, therefore reaffirming importance of SOFA (Sequential Organ Failure Assessment) and qSOFA (quick SOFA) scores as tools to assess the condition of the patients. These scores are used to track the status and outlook of patients with sepsis.
Possible Complications When Diagnosed with Systemic Inflammatory Response Syndrome
Systemic inflammatory response syndrome can escalate, leading to various health complications. This can progress from sepsis (for an infectious cause) to severe sepsis, then shock and multiorgan dysfunction syndrome. These complications can also be related to problems in individual organs. Some notable complications include:
- Brain – Sudden onset of severe confusion or disorientation (acute encephalopathy)
- Lungs – Severe shortness of breath and damage to the lung tissue (ARDS), sudden breathing problem due to aspiration related to brain confusion
- Heart – Increased heart stress causing high troponin levels, rapid heart rhythm
- Digestive system – Stress ulcers, sudden liver inflammation
- Kidneys – Sudden kidney damage and failure, increased acid in the bloodstream, problems with salts and minerals in the body
- Blood – High or low platelet count, abnormal blood clotting, blood cells breaking apart, deep vein clots
- Endocrine System – High blood sugar, sudden adrenal gland failure
Preventing Systemic Inflammatory Response Syndrome
In cases of SIRS (Systemic Inflammatory Response Syndrome) and sepsis, quick detection is crucial for a good recovery. It’s very important to educate patients who are at high risk and their families about early warning signs. Specifically, this applies to individuals who have their immune systems suppressed naturally or due to other conditions.
When treating these conditions, it’s beneficial to teach close family members and patients, if they can participate, about their specific prognosis, potential complications, benefits and risks of treatment. This can significantly reduce harmful stress reactions.
Furthermore, it’s key to understand how the patient or their family members are handling the situation and their anxieties towards diagnostic and therapeutic procedures they may not know much about. If needed, having the support of palliative care personnel or pastoral care for emotional assistance can actually be very helpful.
