Case 6

With a plasma free hemoglobin of 110 mg/dL, this qualifies as severe hemolysis (>100 mg/dL or >1 g/L). Moderate hemolysis is defined as 50–100 mg/dL. 

The three mechanisms of organ injury are: 

(1) Direct nephrotoxicity—free hemoglobin precipitates in renal tubules and induces tubular necrosis, which explains this patient’s rising creatinine. 

(2) Nitric oxide scavenging—free hemoglobin binds nitric oxide, causing vasoconstriction and increasing both systemic and pulmonary vascular resistance. 

(3) Platelet and endothelial dysfunction—nitric oxide depletion impairs platelet and endothelial function, facilitating the formation of microthrombi. 

All three mechanisms can contribute to RV dysfunction.

Answer: D. The most likely driver is excessively negative drainage pressures. The drainage pressure of −380 mmHg is significantly elevated from the baseline of −220 mmHg, indicating the pump is working harder to pull blood. At 3,800 RPM to maintain 4.8 L/min, the high RPMs are generating extreme negative pressures that cause shear stress and destroy red blood cells. This may represent an evolving drainage insufficiency where the pump speed was increased to maintain flow targets, creating a vicious cycle of worsening negative pressures and hemolysis. 

Air entrainment (A) can cause hemolysis but there are no clinical signs suggesting air. Incompatible transfusion (C) and HIT (B) do not explain the circuit-related findings.

The relationship is a vicious cycle: drainage insufficiency (from any cause—hypovolemia, cannula malposition, etc.) leads to reduced venous return to the drainage cannula. In response, the clinical team may increase pump speed (RPMs) to maintain target blood flow. Higher RPMs generate more negative drainage pressures. Exposure of blood to these extreme negative pressures causes shear stress that destroys RBCs, producing hemolysis. Additionally, extremely negative pressures may induce cavitation—the formation of microbubbles from dissolved gas—which produces microthrombi. 

To interrupt this cascade: 

(1) Do not reflexively increase RPMs when flow drops—instead, investigate and treat the underlying cause of drainage insufficiency. 

(2) Accept lower blood flow targets if the patient can tolerate it. 

(3) If flow requirements cannot be met safely, add a second drainage cannula (VV-V) rather than pushing RPMs higher.

If hemolysis persists after addressing the suspected cause: 

(1) Perform a thorough circuit check for occult clot, particularly in the pump head and membrane lung, which could be causing turbulence and shear stress not visible externally. 

(2) Check for air entrainment as a contributing cause. 

(3) If no clear etiology is identified, proceed with a circuit exchange—the circuit may have subclinical thrombus or impeller damage not apparent on inspection. 

(4) If toxic levels of plasma free hemoglobin persist even after circuit exchange, plasmapheresis can be considered to directly remove free hemoglobin from the blood and reduce the burden of nephrotoxicity and NO scavenging.

Answer: A. Free hemoglobin binds nitric oxide, which is a vasodilator. By scavenging NO, free hemoglobin causes vasoconstriction (not vasodilation), increasing both pulmonary and systemic vascular resistance. The increased PVR in particular can precipitate or worsen RV dysfunction, which is especially problematic in ARDS patients who already have elevated pulmonary pressures. 

Choice C is incorrect because hemolysis causes organ injury through multiple mechanisms (nephrotoxicity, NO scavenging, and microthrombi), not just renal injury. Choice B has the vasomotor effect backward. Choice D is incorrect because cavitation is less commonly seen with modern non-occlusive centrifugal pumps.