Critical Care Nephrology: Core Curriculum 2020

Abstract

The intensive care unit (ICU) is a common source of high-acuity nephrology consultations. Although advanced chronic kidney disease is associated with increased ICU mortality, the prognosis of acute kidney injury (AKI) requiring renal replacement therapy is far worse, with short-term mortality rates that often exceed 50%. As such, it is essential that practicing nephrologists be comfortable caring for critically ill patients. This Core Curriculum article emphasizes the developments of the last decade since the last Core Curriculum installment on this topic in 2009. We focus on some of the most common causes of AKI in the critical care setting and use these AKI causes to delve into specific topics most relevant to critical care nephrology, including acute respiratory distress syndrome, extracorporeal membrane oxygenation, evolving concepts in fluid management, and shock. We conclude by reviewing the basics of palliative care nephrology and dialysis decision making in the ICU.

Keywords: Acute kidney injury (AKI); abdominal compartment syndrome; acute liver failure; acute respiratory distress syndrome (ARDS); cardiac surgery–associated AKI; continuous renal replacement therapy (CRRT); critical care nephrology; extracorporeal membrane oxygenation (ECMO); fluid overload; intensive care unit (ICU); intraabdominal hypertension; intravenous fluids; palliative care; respiratory failure; review; sepsis; shock.

Figure 1.

AKI-induced distant organ effects. AKI leads to changes in distant organs, including brain, lungs, heart, liver, gastrointestinal tract, and bone marrow. Changes have been described in organ function, microvascular inflammation and coagulation, cell apoptosis, transporter activity, oxidative stress, and transcriptional responses. Abbreviations: AKI, acute kidney injury; G-CSF, granular colony-stimulating factor; GFAP, glial fibrillary acidic protein; GSH, glutathione; IL-1, interleukin-1; KC, keratinocyte-derived chemokine; TNF-α, tumor necrosis factor-α. Originally published by Scheel et al., Kidney Int. 2008

Figure 2.

(A) Sepsis results in the release of damage- and pathogen-associated molecular patterns (DAMPs and PAMPs) which are filtered at the glomeruli. (B) These “danger signals” can lead to significant microcirculatory dysfunction, which is manifest by heterogeneity of flow. A number of capillaries begin to exhibit sluggish flow, which may lead to amplification of “danger signals” in these areas and lead to increased oxidative stress. In addition, expression of TNF receptors in the S2 segment tubular cells has led to the hypothesis that S1 cells may signal distal segments in a paracrine fashion through secretion of TNF-alpha. Finally, there is also data suggesting that this paracrine signal may also include mediators of cell cycle arrest, namely TIMP-2 and IGFBP-7. (C) Paracrine stimulation from S1 segment tubular epithelial cells produces an oxidative outburst in the S2 and S3 segment tubular epithelial cells. This oxidative outburst can potentially alter mitochondrial function by uncoupling respiration, which in turn leads to energetic imbalance, radical oxygen and nitrogen species (ROS/RNS) production, and loss of mitochondrial membrane potential. Apoptosis may be avoided through reduced energy utilization, mitophagy, and cell cycle arrest. Finally, down-regulated apical ionic transport leads to chloride accumulation which triggers tubuloglomerular feedback (TGF) and subsequent constriction of the afferent arteriole, leading to decreased glomerular filtration rate. Figures adapted from Gomez et al., Shock. 2014

Figure 3.

Proposed classification of vasoactive agents (3a) and schematic of the type and strength of the vascular response each produces (3b). Adrenergic inoconstrictors stimulate β₁ and α₁ receptors to induce increased inotropy and vasoconstriction, respectively. Of note, epinephrine, in addition to β₁ and α₁ activity, has significant β₂ activity, but nonetheless acts as a vasoconstrictor due to the dominant effect of α₁-mediated vasoconstriction; however, β₂-mediated relaxation of smooth muscle by epinephrine is clinically important in the setting of anaphylaxis where it acts to induce bronchodilation. Pure vasoconstrictors include the pure α₁ agonist phenylephrine and the non-adrenergic agent vasopressin, which acts on V₁ receptors on vascular smooth muscle cells; angiotensin II [not-depicted] is a second recently approved non-adrenergic pure vasoconstrictor that acts on AT₁ receptors on vascular smooth muscle. Inodilators include dobutamine, which increases inotropy via β₁ stimulation and induces vasodilation via vascular β₂ receptors; milrinone is another inodilator which acts similarly via phosphodiesterase-3 inhibition. Effects in the case of epinephrine and dopamine depend in part on dose (LD, low-dose; HD, high-dose). Figures adapted from Jentzer et al.

Figure 4.

Pathological sequelae of fluid overload in organ systems. Prowle et al., Nature Reviews Nephrology 2010

Figure 5:

Changing fluid resuscitation strategies parallel the phases of critical illness and the immune response to sepsis or another injury. Phase A (0 to 6 hours): initial aggressive volume resuscitation (e.g., 30 cc/kg of IV crystalloid), also known as the ebb phase of critical illness. Phase B (6 to 36 hours): decelerating fluid resuscitation; fluid is often still required to compensate for extravascular sequestration, but fluids should only be provided as needed to maintain organ perfusion in a targeted manner, with frequent reassessment of fluid responsiveness. Phase C (36 to 48 hours): equilibrium phase; fluid administration is stopped. Phase D (beyond 48 hours): mobilization, deresuscitation, or flow phase; fluids are withheld to allow for spontaneous diuresis or, in those who fail to auto-diurese, pharmacologic diuresis or ultrafiltration can be provided to achieve euvolemia. The time at which a given patient transitions from one phase to the next may be variable and multiple insults can substantially disrupt this sequence. Adapted from Godin et al.

Figure 6.

Schematics of (A) VV-ECMO, (B) VA-ECMO, and (C) integrated ECMO and CRRT circuits. In VV-ECMO (A), venous drainage is via a large multiport cannula introduced via the femoral vein and advanced to the hepatic IVC just below the IVC-RA junction. The blood then passes through a centrifugal pump followed by a membrane oxygenator prior to returning to the body via a catheter that is placed through the right internal jugular and SVC and terminates in the RA. In VV-ECMO, the tips of the two cannulae must be maintained a minimum distance apart to prevent recirculation (inset). In VA-ECMO (B), oxygenated blood is returned via the left femoral artery and travels retrograde up the aorta towards the great vessels and mixes with blood leaving the LV. In this example, a distal reperfusion cannula (R) also carries oxygenated blood from the return cannula and infuses it into the left femoral artery beyond the cannulation site to prevent distal left lower extremity ischemia. (C) The inflow to a separate CRRT device is ideally connected to a post-pump segment of the ECMO circuit so that the risk of entrainment of air from the CRRT circuit into the ECMO circuit is minimized by the high positive circuit pressure; the outflow from the CRRT is ideally connected to a pre-oxygenator segment of the ECMO circuit to allow the oxygenator to filter out any air or clots coming from the CRRT device. Figures A and B are adapted from Banfi et al. Figure C is adapted from Santiago et al. Abbreviations: AC, arterial cannula; IVC, inferior vena cava; LV, left ventricle; R, reperfusion cannula; RA, right atrium; SVC, superior vena cava; TV, tricuspid valve; VC, venous cannula.