# Situation: A 52-year-old man is in the intensive care unit (ICU) with septic shock and acute kidney injury. He is intubated and receives mechanical ventilation. Because his platelet count is low, he is on continuous kidney replacement therapy (CRRT) with regional citrate anticoagulation. Earlier, on day 3 of CRRT, as his sedation was lightened, he nodded that his lips tingled; the nurse also noted muscle twitching and a newly prolonged QT interval on the monitor. Results: - Ionized calcium 0.86 mmol/L (normal 1.12–1.32 mmol/L) - Total serum calcium 9.4 mg/dL (normal 8.6–10.2 mg/dL) - Magnesium 2.0 mg/dL (normal 1.7–2.2 mg/dL) Which conclusion do these findings support?

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> subject: Nursing Practice V — Care of Clients with Maladaptive Patterns of Behavior; Care of Clients with Life-Threatening Conditions, Acute Multi-Organ Problems, High Acuity and Emergency Situations

## 문제

Situation: A 52-year-old man is in the intensive care unit (ICU) with septic shock and acute kidney injury. He is intubated and receives mechanical ventilation. Because his platelet count is low, he is on continuous kidney replacement therapy (CRRT) with regional citrate anticoagulation.

Earlier, on day 3 of CRRT, as his sedation was lightened, he nodded that his lips tingled; the nurse also noted muscle twitching and a newly prolonged QT interval on the monitor. Results:
- Ionized calcium 0.86 mmol/L (normal 1.12–1.32 mmol/L)
- Total serum calcium 9.4 mg/dL (normal 8.6–10.2 mg/dL)
- Magnesium 2.0 mg/dL (normal 1.7–2.2 mg/dL)
Which conclusion do these findings support?

## 보기

1. No calcium disorder, since total calcium is in the normal range
2. Hypomagnesemia from magnesium loss into the effluent fluid
3. Low ionized calcium from citrate reaching his bloodstream **✔ 정답**
4. Hypercalcemia from the calcium infusion into the return line

**정답: 3**

## 해설

Citrate anticoagulates the circuit by binding ionized calcium. When citrate returns to the client faster than it is metabolized, as can happen in septic shock, it keeps binding calcium in his blood: ionized calcium falls while total calcium stays normal or rises, because calcium bound to citrate is still counted in the total. Only ionized calcium is physiologically active, so tingling, twitching and QT prolongation reflect true hypocalcemia; the nurse reports it for adjustment of calcium replacement or the citrate dose per protocol.

## 심화 해설

Core conclusion

The findings support systemic citrate accumulation with ionized hypocalcemia. The ionized calcium of 0.86 mmol/L is below the normal range of 1.12–1.32 mmol/L, while the total serum calcium of 9.4 mg/dL remains within the normal range of 8.6–10.2 mg/dL. This discordance is the hallmark of citrate binding calcium in the bloodstream rather than a true total-body calcium deficit.

Why total calcium can be normal while ionized calcium is low

Citrate works as a regional anticoagulant by chelating ionized calcium within the extracorporeal circuit. Under normal conditions, the citrate–calcium complex is largely removed by the hemofilter or metabolized in the liver, skeletal muscle, and kidney, and the bound calcium is released back into circulation [2]. However, when citrate delivery exceeds the combined metabolic and extracorporeal clearance capacity, citrate accumulates systemically [1][2]. Once in the patient’s bloodstream, citrate continues to bind ionized calcium, forming calcium–citrate complexes. These complexes remain in the plasma and are still measured as part of the total serum calcium, so the total calcium may appear normal or even elevated while the physiologically active ionized fraction falls [3].

Only ionized calcium is physiologically active; the calcium bound to citrate is counted in the total calcium but cannot participate in neuromuscular or cardiac function. This explains why the client developed perioral tingling, muscle twitching, and QT prolongation despite a normal total calcium level.

Why this client is at risk for citrate accumulation

This client has septic shock and acute kidney injury. Septic shock impairs hepatic perfusion and mitochondrial oxidative metabolism, which are the primary pathways for citrate clearance [2][4]. Acute kidney injury further reduces the renal contribution to citrate metabolism. In addition, the client’s low platelet count was the reason regional citrate anticoagulation was chosen over heparin, but that same critical illness reduces the body’s ability to handle the citrate load. When citrate returns to the bloodstream faster than it can be metabolized or removed by the filter, it continues to bind calcium systemically, producing ionized hypocalcemia.

Differential interpretation of the other options

| Option | Why it is incorrect |
| --- | --- |
| 1. No calcium disorder | Total calcium is normal, but the ionized calcium is clearly low. Ionized calcium, not total calcium, determines neuromuscular and cardiac stability. |
| 2. Hypomagnesemia | Magnesium is 2.0 mg/dL, within the normal range of 1.7–2.2 mg/dL. There is no evidence of magnesium loss into the effluent in this scenario. |
| 4. Hypercalcemia from calcium infusion | The ionized calcium is low, not high. Calcium replacement given into the return line is intended to replace calcium lost through the filter, but it does not explain a low ionized calcium. |

Clinical recognition of citrate toxicity

The signs in this client—perioral tingling, muscle twitching, and a newly prolonged QT interval—are consistent with ionized hypocalcemia. In the setting of regional citrate anticoagulation, ionized hypocalcemia can arise from two distinct mechanisms: systemic citrate accumulation or net calcium loss from plasma through the hemofilter [3]. The combination of a low ionized calcium with a normal or elevated total calcium points specifically to systemic citrate accumulation rather than simple calcium loss, because calcium lost through the filter would lower both ionized and total calcium over time unless replacement is inadequate.

Key point! A normal total calcium does not rule out clinically significant hypocalcemia during regional citrate anticoagulation. The ionized calcium must be monitored directly.

Watch out! In septic shock with impaired liver perfusion, citrate metabolism is reduced, so even a standard citrate infusion rate can produce systemic accumulation.

Nursing and interprofessional implications

The nurse should recognize the constellation of low ionized calcium, normal total calcium, and neuromuscular or electrocardiographic changes as evidence of citrate reaching the systemic circulation. The response includes notifying the provider and the CRRT team so that the citrate dose can be reduced, the calcium replacement rate can be adjusted, or the dialysate and blood flow rates can be modified according to protocol [1][3]. Serial ionized calcium monitoring and assessment for worsening signs such as hypotension, arrhythmias, or progressive acid–base disturbance are priorities. The underlying problem is not a simple calcium deficit but an imbalance between citrate delivery and citrate clearance in a critically ill patient.References (research sources)

- [1]Systemic Citrate Toxicity During Regional Citrate Anticoagulation for Continuous Kidney Replacement Therapy.Research articleRedant S, Attou R, Talpos MT, Honoré PM. (2026) · DOI: 10.3390/jcm15176564

- [2]Systemic Citrate Toxicity During Regional Citrate Anticoagulation for Continuous Kidney Replacement TherapyResearch articleRedant S, Attou R, Talpos MT, Honoré PM. (2026) · DOI: 10.20944/preprints202607.0291.v1

- [3]Troubleshooting Ionized Hypocalcemia in Patients on Continuous KRT with Regional Citrate Anticoagulation.Research articleYessayan L, Tolwani A, Heung M, Szamosfalvi B (2026) · DOI: 10.34067/KID.0000001053

- [4]Citrate accumulation during regional citrate anticoagulation for continuous renal replacement therapy: a narrative review.Research articleChen Y, Zhang J, Chen Z. (2026) · DOI: 10.1080/0886022x.2026.2725350

## 임상 시나리오

Citrate Accumulation in CRRTRecognizing ionized hypocalcemia with normal total calcium
In septic shock, citrate metabolism is impaired, so citrate returning to the bloodstream continues to bind ionized calcium. This lowers ionized calcium below 1.12 mmol/L while total calcium remains normal or rises because citrate-bound calcium is still counted in total calcium.

Only ionized calcium is physiologically active. Signs such as perioral tingling, muscle twitching, and QT prolongation reflect true hypocalcemia and require prompt reporting for adjustment of calcium replacement or citrate dose.

CautionDo not rely on total calcium alone during citrate CRRT. A normal or high total calcium can mask life-threatening ionized hypocalcemia, so monitor ionized calcium and ECG changes closely.

## 핵심 개념

- **Ionized calcium** — The physiologically active fraction of calcium; normal range is 1.12–1.32 mmol/L.
- **Total serum calcium** — Includes both free and protein- or citrate-bound calcium; normal range is 8.6–10.2 mg/dL.
- **Citrate anticoagulation** — Regional anticoagulation for CRRT that chelates ionized calcium in the circuit to prevent clotting.
- **Citrate accumulation** — Occurs when citrate delivery exceeds metabolism and clearance, causing systemic ionized hypocalcemia.
- **QT prolongation** — A cardiac conduction abnormality that can result from hypocalcemia, increasing risk of arrhythmia.

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