One discussion this week included atelectasis as a potential cause of postoperative fever.

Reference: Crompton JG, Crompton PD, Matzinger P. Does atelectasis cause fever after surgery? Putting a damper on dogma. JAMA Surgery. 2019 Mar 6:154(5):375-376. doi:10.1001/jamasurg.2018.5645.

Summary: Fever and atelectasis are common after surgery, and in the absence of infectious causative mechanisms, atelectasis is commonly thought to be a cause of fever. The therapeutic implication of atelectasis as a putative cause of postoperative fever has been the widespread adoption of incentive spirometry to reduce atelectasis.

Crompton et al (2019) propose an alternative explanation—the danger model of immunity—to explain how fever may develop after surgery in the absence of a clear pathogen. According to this theory, an immune response is initiated when cells are injured or distressed. They believe this self-limiting inflammatory response better accounts for noninfectious postoperative fever than atelectasis, and suggest that current treatment to reduce fever with incentive spirometry may not be necessary.

The molecular mechanism most commonly cited to support a causal role for
atelectasis in postoperative fever is increased production of fever-inducing cytokines suchas interleukin 1 (IL-1) or tumor necrosis factor by alveolar macrophages. This is based on a study in which whole-lung atelectasis was modeled in rats by ligating the left main stem bronchus while maintaining ventilation of the right lung. Alveolar macrophages were subsequently harvested, and in vitro assays showed increased production of IL-1 and tumor necrosis factor. According to the danger model, it may
be that the alveolar macrophages in this study were not responding to atelectasis per se but rather to the tissue damage caused by the surgery.

The danger model of immunity

Based on the assumption that the immune system responds to things that create damage and does not respond to any entity, whether self or nonself, that does not create damage.

The idea is that damaged cells send alarm signals that activate innate immune cells. Thus, immunity to transplant is initiated by preparation of the donor organ and stress of surgery; immunity to cancer occurs with tumor necrosis; autoimmunity occurs because of inappropriate alarm signals or their receptors; and the distinction between commensal organisms and pathogens lies with their tendency to produce tissue damage. The alarm signals are termed damage-associated molecular patterns(DAMPs).

DAMPs, similar to PAMPs, trigger immune cells to release pyrogenic cytokines such
as IL-1 and IL-6, which induce fever by acting on the hypothalamus. The fever is a result of tissue damage, whether from pathogens, surgery, trauma, or other mechanisms whereby DAMPs are released.

THERAPY: The danger model provides an understanding of noninfectious postoperative fever that is not owing to atelectasis and does not require treatment with incentive spirometry. In the absence of symptoms or signs of infection such as leukocytosis, the authors believe that  early postoperative fever can be attributed to DAMPs, not PAMPs— a physiologic self-limiting phenomenon that does not require therapeutic intervention.