ICIS – a read-out of the immune system
Is it a bacterial infection or something else? The RUO* Intensive Care Infection Score (ICIS) has the potential to provide decisive support for diagnostics. We spoke to Dr Andreas Weimann about the ICIS.*
Dr Weimann, you co-developed the ICIS.* What makes this score so useful in intensive care medicine?
Critical care medicine specialists need to know as soon as possible whether an infection is present or not, and whether it is still localised or has already spread. And then there’s the question of the differential analysis: is the cause bacterial, viral or fungal? If the patient has a fever, antibiotics are often prescribed. The important thing is to start anti-infective chemotherapy only when necessary, to minimise any side effects and of course, avoid the emergence of multiresistant pathogens. Blood culture analysis is usually slow to provide results, and often gives no result at all. But you almost always get an answer from this ICIS,* which almost seems to ‘talk’ to you. For me, it’s a direct ‘read-out’ of the immune system. It shows the direct reaction of the patient, and whether or not the patient is responding in an immunocompetent fashion. The blood count is available to me around the clock, always fast, standardised and cost-effective. That is why I think the ICIS* is brilliant as, in general, the extended blood parameters. After all, blood is a ‘special juice’ which contains cells that fight the infection. Why would you not make use of it?
Why is a new score needed? After all, clinical-chemical parameters such as C-reactive protein (CRP) and procalcitonin (PCT) are better known to diagnose an infection.
CRP is what is known as an acute phase protein, but it can take 48 hours to peak. And only about 24 hours after the onset of the infection does its increase indicate an infection. Given that, in the case of septic shock, mortality rises by about 7% to 8% per hour – and by much more than that in neonates – the excessively slow kinetics of CRP limits its value for acute treatment.
As for PCT, we still don’t really know what its function is. What we do know, however, is that PCT is not always a reliable marker of infection: a PCT value within the reference interval does not always rule out an infection, and compromised renal function, hyperthyroidism or even haematologic systemic diseases can result in raised PCT concentrations. So, PCT cannot necessarily give me the answers to all the important questions. The crucial thing in everyday clinical practice is that these parameters are available around the clock, as quickly as possible and in a standardised and cost-effective manner.
ICIS* is a score that exclusively uses blood count parameters. How does it work?
What does the conventional complete blood count offer us? For me, in this context, it’s akin to counting peas. White blood cell values encompass a whole range of cell types with different precursor cells, and that simply does not provide enough information for critically ill patients. So, we have to dig deeper. Even the pure lymphocyte count does not distinguish between B and T cells. The conventional complete blood count can tell us about quantity, but not necessarily about the qualitative reactions of cells. For example, it is almost impossible to tell whether certain cells are activated. Sysmex technology, however, can distinguish between a wide variety of cell populations. Detecting highly fluorescent lymphocytes – memory B cells – can be a decisive indication of an infection. If malignant plasma cells are excluded, I can assume a pathogen-induced response, which gives me a highly specific marker of sepsis, although that still does not tell me whether the cause is viral or bacterial. Neutrophil activity helps me to make that distinction. Neutrophils are part of the innate immune system and react to bacteria and fungal pathogens, but not to viruses. This makes it easier to make a treatment decision. However, it is also important to consider the patient’s history and consider whether a drug or other therapy agent might be interfering with the technology used for measurement. In some cases, active ingredients can influence a cell’s characteristics, which can lead to higher values.
In your opinion, what are the most important parameters of the score?
For me, one of the most important parameters of the score is Delta-He – the ‘reticulocyte-haemoglobin minus haemoglobin of mature red blood cells’. Around 15 years ago, I had absolutely no idea that the red blood cell count could provide information about the status of an intensive care patient. When we observed that the haemoglobin content of reticulocytes could change within just three to four hours of adjusting treatment, that was a completely new finding. Moreover, Delta-He reacts much more strongly to bacterial infections than to viral ones. This is generally due to the lower concentration of interleukin-6 (IL-6) in viral infections, although there are some exceptions. IL-6 stimulates the release of hepcidin, resulting in reduced iron absorption and utilisation. I always refer to this process as the ‘iron immune system’.
How do you envisage the ICIS* being used in routine practice?
Determining the baseline value would be hugely important: ideally, this should take place on admission, before any major interventions like surgery. Then the ICIS* value should be monitored at least daily, because ultimately the ICIS* is highly dynamic. This would allow me to monitor the effectiveness of antibiotic therapy, for example, even though there is often a long wait for the pathogen to be diagnosed directly.
What cut-off value should be used?
I would be very cautious about specifying an absolute cut-off value. For me, the decisive factor is the trend in the patient’s values over time. Where possible, the ICIS should not be calculated for the first time postoperatively in the intensive care unit if sepsis is suspected; instead, a preoperative baseline score should be determined on initial admission.
*RUO stands for ‘research use only’, meaning that the manufacturer has not specified an intended purpose for in vitro diagnostics. Internal validation in clinical settings is therefore required before information can be used to make a diagnosis or decide on treatment. Optional application, depending on software version.
