Exploring the possibilities of immune protective surgery in trauma and beyond

Severe trauma, major surgery, and fractures in vulnerable elderly patients elicit a systemic innate immune response. Trauma should therefore be regarded not merely as a collection of local injuries, but as a condition affecting the entire body. The initial immune response to tissue damage, often referred to as the “first hit,” aims to restore tissue integrity and prevent infection. However, an excessive or dysregulated response may lead to complications such as infections, organ failure, or impaired recovery. Subsequent surgical interventions may act as a “second hit,” further amplifying this response and increasing the risk of adverse outcomes. Notably, patients with comparable injury severity do not exhibit identical immune responses, highlighting substantial interindividual variability. Understanding this variability is essential for early identification of high-risk patients and for tailoring clinical decision-making.
Neutrophils play a central role in the early immune response following trauma. After severe injury, both their phenotype and function undergo profound changes. Circulating neutrophil populations shift towards immature, banded forms due to emergency granulopoiesis, while later stages are characterized by the emergence of hypersegmented subsets. These alterations are associated with functional changes, including impaired responsiveness to bacterial stimuli such as formyl peptides, reflecting a dysregulated immune state and increased susceptibility to infections.
These dynamic changes can be captured by measuring neutrophil surface markers using flow cytometry. The introduction of fully automated, near-patient flow cytometry enables rapid and reliable immune monitoring within minutes, without the need for extensive sample processing. This approach minimizes ex vivo activation and allows implementation in acute clinical settings.
Using this technology, distinct neutrophil phenotypes have been identified shortly after trauma and surgery. In particular, the presence of immature CD16^low/CD62L^low neutrophils is associated with an increased risk of infectious complications and adverse outcomes, even when conventional clinical parameters do not indicate elevated risk. Importantly, the magnitude of the immune response does not consistently correlate with anatomical injury severity, underscoring the added value of direct immune monitoring.
Beyond trauma, similar immune alterations are observed following major elective surgery, with more pronounced responses after extensive abdominal procedures compared to cardiac surgery. In geriatric trauma populations, neutrophil phenotyping offers opportunities for improved risk stratification and may support shared decision-making, particularly in patients with limited physiological reserve.
Neutrophil phenotypes can be classified visually using CD16/CD62L expression patterns into distinct categories reflecting increasing levels of immune activation. This approach demonstrates good interobserver reliability, particularly when simplified into a binary classification, and is feasible for clinicians without extensive expertise in flow cytometry.
Future implementation requires further standardization and integration into clinical workflows. Large-scale initiatives, such as the international PREDICT collaboration, aim to develop predictive models based on neutrophil phenotypes. The incorporation of automated interpretation algorithms represents a logical next step toward scalable application.
Ultimately, near-patient neutrophil profiling enables real-time assessment of the immune response and supports a shift toward immune-guided clinical decision-making. This concept of immune-protective surgery offers the potential to reduce complications, optimize timing and extent of interventions, and personalize care in trauma and beyond.