What is the impact of sepsis on our health systems from both a medical and financial point of view?
First of all, sepsis is a global healthcare problem which affects more than 25 million patients a year.
Sepsis can easily escalate to the life-threatening condition septic shock which has a mortality rate of about 40 %. In most cases, patients expire during intensive treatment in the ICU, after a long fight against the infection and a constantly decreasing function of vital organs.
Patients with septic shock have a high ICU mortality rate and long ICU length of stay and are substantially expensive to treat. It’s especially these days of intensive treatment of sepsis in the ICUs which make this disease costly and a significant burden to our health system.
However, non-surviving septic patients are in fact more costly than survivors despite shorter ICU length of stay due to higher medication costs from the increased efforts to keep patients alive.
How do sepsis patients present in the intensive care unit?
Patients referred to the ICU might be in a situation when infection and sepsis have been diagnosed or at least suspected, often referred from other departments in the hospital including the emergency department. In such cases, measures should already have been initiated to stabilize the circulation and ensure adequate organ perfusion. The infection should already be under treatment with antibiotics.
In other cases, sepsis might not have been diagnosed yet or might have emerged during the stay in intensive care. In these cases, it’s eminent that sepsis is recognized and diagnosed quickly to prevent any delay in treatment, increasing the odds for survival. Delaying antibiotic treatment in septic shock patients has shown to increase mortality with 7 % for every hour of delay.
How is sepsis then diagnosed in the intensive care unit?
Recently, several intensive care organizations have published the new definition and clinical profile of sepsis and septic shock, Sepsis-3. In short, it defines sepsis as organ dysfunction caused by infection. So for diagnosis of sepsis we need to show presence of infection and organ dysfunction.
Organ dysfunction is assessed by serial determination of the sequential organ function assessment or SOFA score. This reflects a panel of various laboratory and physical measurements, each with an increasing score when an organ is affected. An increase of at least 2 points reflects a significant worsening of organ function.
Alternatively, you can use the so-called “quick-SOFA indicators”, or qSOFA, to easily and quickly assess three markers; altered mental status, respiratory rate greater than or equal to 22 breaths/min and systolic blood pressure less than or equal to 100 mm Hg. At least 2 of these need to be positive to indicate a high risk of underlying organ dysfunction.
Lactate levels also help in the diagnosis of sepsis, with levels >2 mmol/L indicating hypoperfusion of the organs. When vasopressors are required to maintain a mean arterial pressure of over 65 mm Hg and lactate levels remain >2 mmol/L, sepsis has progressed to septic shock, a very serious condition associated with a very high level of mortality. Lactate levels indicate the progression of sepsis and are measured regularly to monitor progression of disease and the effects of treatment.
Which tools are available to diagnose infection?
Even with sophisticated tools available based on nucleic acid testing or proteomics, most bacterial and fungal infections are diagnosed and characterized by positive culture results. Unfortunately, these cultures require one to three days before results are reported which is far too late to wait to start any antimicrobial treatment. Especially when patients are suspected of infection, they need to receive empiric antibiotics as soon as possible.
Traditional blood cultures are not very helpful, not only because they are slow, but also because they have limited sensitivity and specificity. This is where a biomarker like procalcitonin (PCT) adds value in the management of sepsis in the ICU, as it can detect bacterial and fungal infections faster and with great diagnostic accuracy. Procalcitonin can be used to trigger antibiotic therapy before the pathogen has been identified.
What challenges does sepsis create in the ICU?
The main challenge is to prevent patients from progressing to septic shock. To maintain adequate blood flow and oxygenation of vital organs, it’s of utmost importance to effectively treat any infection and eliminate the pathogen from circulation. The most prevalent infections causing sepsis are bacterial or fungal, and it’s therefore essential to confirm such an infection quickly and start effective antibacterial or antifungal treatment.
Where do you see the major advantages of using procalcitonin in the ICU?
It really depends on the status of the patient. If sepsis has not been diagnosed yet, the level of PCT will help to identify patients with either a very limited or high risk of having an infection. In the cases when a patient has not received any antibiotic treatment, increased levels of PCT will alarm clinicians and support better treatment of the patient.
In case sepsis has already been diagnosed and antibiotic therapy is in place, regular PCT results will indicate whether the antibiotic treatment is successful or not. Decreasing PCT levels indicate successful therapy, while persistent high or increasing PCT levels indicate treatment failure. In such cases, alternative antimicrobial treatment needs to be considered. Moreover, treatment failure might indicate bacterial resistance which would require immediate attention.
Often, however, sepsis and infection are merely suspected and antibiotic therapy is initiated on a “better safe than sorry” basis. These patients can demonstrate consistently negative or very low PCT levels in ICU, indicating that bacterial infection is highly unlikely and that antibiotic therapy is therefore not indicated and can be stopped safely.
Such information will not only reduce the unnecessary use of antibiotics, but also help clinicians in refocusing to find the real cause of the patient’s symptoms. Moreover, reducing unnecessary antibiotic use also reduces the time a patient is exposed to selective pressure and the risk a resistant bacterial strain will emerge.
In short, studies continue to show that guiding antibiotic therapy based on the dynamics of PCT levels in the blood will reduce not only the use of antibiotics but also the length of stay, hereby lowering hospital costs significantly.
Are there any limitations to using PCT in the ICU?
Yes. Although the sensitivity of PCT for bacterial and fungal infections is great, we need to be aware that sensitivity for viral infections is limited. Patients might have sepsis and demonstrate almost normal PCT results in the ICU, because the pathogen is a virus. It’s therefore of utmost importance to take all clinical and diagnostic information into account before diagnosing and treating a patient.
About Radiometer and the company’s commitment to fight sepsis
Committed to joining the fight against sepsis, Radiometer is sponsoring the World Sepsis Congress and the World Sepsis Day. Radiometer offers the broadest point-of-care diagnostic menu to support the current guidelines for the diagnosis and treatment of sepsis, including full blood gas analysis, lactate, PCT, CRP, WBC and more.
To find out more about Radiometer’s portfolio of acute care tests, please contact radiometer@radiometer.com or visit www.radiometer.com.
Find in-depth articles on infection and sepsis on the scientific knowledge site acutecaretesting.org.
About Jordi Trafi
Jordi Trafi is the Global Marketing Director at Radiometer for the AQT90 FLEX analyzer, Radiometer’s platform for testing of biomarkers in point-of-care settings. Originally studying pharmacy, Jordi has worked 24 years in the in vitro diagnostic industry, including companies as Boehringer Mannheim (now Roche), Dade Behring (now Siemens), Siemens and Radiometer.
He has visited hundreds of clinical laboratories and point-of-care settings either as clinical application specialist or marketing responsible, identifying the clinical needs that the in vitro diagnostic products should satisfy.
His areas of expertise include cardiac and infection biomarkers, drug of abuse testing, therapeutic drug monitoring and immunoassay and clinical biochemistry technologies.