Higher calprotectin levels identify ED sepsis patients requiring direct intensive care transfer

10th March 2023

A study suggests that calprotectin could be a useful biomarker for identifying sepsis patients who require intensive care transfer from ED

A prospective study by researchers at the Karolinska University Hospital, Stockholm, Sweden, has revealed that elevated plasma calprotectin levels was superior to other biomarkers for the identification of emergency department (ED) patients with sepsis who required urgent transfer to either an intensive care (ICU) or high dependency unit (HDU).

In data for 2017, it was reported that globally, there were an estimated 48.9 million incident cases of sepsis and which led to 11 million deaths. Moreover, it is also recognised that the early detection of sepsis results in greater patient survival. Calprotectin is a protein present in the cytoplasm of neutrophils and levels have been found to increase early in response to a bacterial challenge and in fact, other work demonstrates how serum calprotectin levels are a reliable biomarker in patients with bacterial sepsis. Nevertheless, while measurement of serum calprotectin levels is of value in sepsis, whether the biomarker serves to identify ED sepsis patients who required direct transfer to an ICU or HDU is less clear.

In the current study, the Swedish team turned to patients ED patients identified as likely to have sepsis based on an alert system used within the department, i.e., those with signs of organ dysfunction and symptoms of infection. Among such patients, blood samples were analysed for several biomarkers including C-reactive protein, procalcitonin, neutrophils, lymphocytes and calprotectin which was analysed from frozen plasma samples. The researchers set the primary outcome as direct transfer to an ICU or HDU from the ED, based on the decision of the multidisciplinary team.

Calprotectin levels and ED to ICU transfer

Among a total of 319 patients with a median age of between 71 and 73 (37.5% female) identified with an infection, 26% were immediately transferred to either ICU or HDU and the remainder to a hospital ward.

The overall median calprotectin level was 2.2 mg/L (IQR 1.2 – 3.9 mg/L) for all infected patients but was significantly higher (3.3 vs 2.1, p = 0.0001) among those transferred to either an ICU or HDU compared to a ward.

Using the receiver operating characteristic curve analysis, calprotectin had the highest area under the curve (AUC) at 0.65 compared to C-reactive protein (AUC = 0.55), procalcitonin (AUC = 0.46) and the neutrophil-lymphocyte ratio (AUC = 0.47).

A cut-off value for calprotectin of 4.0 mg/L, gave the best combination of sensitivity (42.5%) and specificity (83%) for the transfer to the ICU/HDU among patients with infection.

The authors concluded that among sepsis alert patients, plasma calprotectin was significantly elevated in patients requiring immediate transfer to ICU or HDU and proved to be superior to other biomarkers for the prediction of such transfers.

Citation
Parke A et al. Plasma calprotectin as an indicator of need of transfer to intensive care in patients with suspected sepsis at the emergency department BMC Emerg Med 2023

Blood lactate levels in tandem with qSOFA or NEWS provides best prediction of 28-day in-hospital mortality for patients at risk of sepsis

27th April 2022

Blood lactate measurements alongside qSOFA or NEWS improves the sensitivities of both tools for predicting 28-day in-hospital mortality

Using blood lactate levels alongside either the quick sequential organ failure assessment (qSOFA) or the National Early Warning Score (NEWS) clinical prediction tools, increases the sensitivities of both for the prediction of 28-day in-hospital mortality among emergency department (ED) patients with a suspected infection and at risk of sepsis.

This was the conclusion of a study by researchers from the Department of Intensive Care, Centre Hospitalier du Mans, Le Mans, France.

The World Health Organization defines sepsis as a life-threatening organ dysfunction caused by a dysregulated host response to infection adding how in 2017, the condition was responsible for around 11 million deaths worldwide, representing almost 20% of all global deaths. Moreover, early detection of sepsis with timely, appropriate interventions increases the likelihood of patient survival.

Consequently, several tools have been developed to assess patients with an infection who are likely to have sepsis including qSOFA and NEWS. However, a 2018 meta-analysis found that qSOFA was associated with a pooled sensitivity of only 60.8% and a pooled specificity of 72.0% for the prediction of mortality.

The NEWS can also be used for predicting intensive care unit (ICU) admission and mortality when used in an ED although a systemic review found that the NEWS area under the receiver operating characteristic curve for mortality prediction, varied from from little better than chance to a good prediction of mortality.

In addition, elevated blood lactate levels (> 2.6 mmol/L) have also been found to predict 30-day in-hospital mortality in unselected patients who arrived at an ED.

Given the potential value of both tools and measurement of blood lactate levels, for the present study, the French team wondered if modification of the qSOFA and NEWS to incorporate lactate levels, would improve their respective predictive accuracy for adult ED patients with suspected infection.

The French team undertook a retrospective analysis of adult patients with suspected infection and who had blood cultures obtained within the ED and to whom a non-prophylactic antibiotic was given within the ED.

They created three separate clinical prediction tools: qSOFA and NEWS alone; both tools with blood lactate levels incorporated and finally, both qSOFA and NEWS with blood lactate levels measured in tandem. Cut-off scores for qSOFA used were > 2 and NEWS > 7 and blood lactate levels > 2 mmol/L.

The primary outcome measure was in-hospital 28-day all-cause mortality and the secondary outcome, 3-day all-cause mortality.

Blood lactate levels and clinical scoring outcomes

A total of 1003 patients with a median age of 76 years (57% male) were included in the study and by day 28, 13% of patients had died in hospital.

The sensitivities for 28-day mortality were 50% (qSOFA > 2), 69% (qSOFA with lactate), 77% (qSOFA and lactate in tandem). For NEWS, the corresponding sensitivities were 69% (NEWS alone), 80% (NEWS with lactate) and 87% (NEWS with lactate in tandem). In other words, using either qSOFA or NEWS and blood lactate levels in tandem, provided greater sensitivities than either of the prediction tools alone or with lactate levels incorporated into the tool. Similar results were seen for the secondary outcome of 3-day all-cause mortality.

Nevertheless, despite the improved sensitivities for both prediction tools when used alongside blood lactate levels, the corresponding specificities were 66% (qSOFA and lactate in tandem) and 46% (NEWS and lactate in tandem). This, the authors suggested meant that neither combination was an effective means of ‘ruling out’ mortality.

They concluded that though using either tool in tandem with blood lactate was better than incorporating lactate levels into the tool, neither tool optimally predicted in-hospital 28-day mortality.

Citation
Julienne J et al. Prognostic accuracy of using lactate in addition to the quick Sequential Organ Failure Assessment score and the National Early Warning Score for emergency department patients with suspected infection Emerg Med J 2022