Sepsis Management for the Nephrologist

Abstract

The definition of sepsis has evolved significantly over the past three decades. Today, sepsis is defined as a dysregulated host immune response to microbial invasion leading to end organ dysfunction. Septic shock is characterized by hypotension requiring vasopressors after adequate fluid resuscitation with elevated lactate. Early recognition and intervention remain hallmarks for sepsis management. We addressed the current literature and assimilated thought regarding optimum initial resuscitation of the patient with sepsis. A nuanced understanding of the physiology of lactate is provided in our review. Physiologic and practical knowledge of steroid and vasopressor therapy for sepsis is crucial and addressed. As blood purification may interest the nephrologist treating sepsis, we have also added a brief discussion of its status.

Keywords: acute kidney injury; critical care nephrology and acute kidney injury series; sepsis; septic shock.

Figure 1.

The evolution of sepsis definitions. SIRS, systemic inflammatory response.

Figure 2.

Antibiotic timing. The timing of antibiotics depends on the presence of shock and the probability of sepsis. Patients with a high probability of sepsis should receive antibiotics within 1 hour. In patients with possible sepsis, antibiotics should be initiated within an hour if shock is present and within 3 hours if they are hemodynamically stable. Reprinted from ref. , with permission.

Figure 3.

In sepsis, the afferent arteriole undergoes vasoconstriction, whereas the efferent arteriole vasodilates, leading to a reduction in glomerular filtration pressure. The differences in resistance between the two arterioles predispose to glomerular shunting via periglomerular shunting pathways. Both mechanisms lead to a reduction in GFR, despite an increase in renal blood flow early in sepsis.

Figure 4.

Sepsis-related kidney injury can be divided into primary and secondary mechanisms. The primary mechanisms include damage-associated molecular patterns (DAMPS) and pathogen-associated molecular patterns (PAMPS), leading to an innate immune response with consequential systemic vasodilation, disseminated intravascular coagulopathy (DIC), and cellular reprogramming of renal tubular epithelial cells. The innate immune response further contributes to microvascular changes and glomerular microthrombi, resulting a net reduction in GFR. Secondary injury occurs due to fluid resuscitation that can lead to venous congestion and intra-abdominal hypertension, which further contributes to AKI.

Figure 5.

The figure illustrates the relationship between oxygen delivery (DO₂) and oxygen consumption (VO₂). As DO₂ decreases, VO₂ remains relatively constant until it reaches a critical O₂ supply dependence threshold, at which point there will be a significant drop in VO₂. Lactate rises prior to the O₂ supply dependence threshold are independent of the DO₂-VO₂ relationship, whereas below the threshold, they become DO₂-VO₂ dependent.