| Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access |
| Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc |
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Original Article
Volume 18, Number 1, January 2026, pages 31-41
Efficacy and Safety of Regional Citrate Anticoagulation in Neurocritical Care Patients With Chronic Severe Hypernatremia Undergoing Continuous Renal Replacement Therapy: A Single-Center Retrospective Study
Figures



Tables
| Variables | Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|---|
| Total (n = 98) | RCA (n = 70) | NA (n = 28) | P | Total (n = 42) | RCA (n = 21) | NA (n = 21) | P | |
| ALB: albumin; AKI: acute kidney injury; APACHE II: Acute Physiology and Chronic Health Evaluation II; aPTT: activated partial thromboplastin time; GCS: Glasgow Coma Scale; Hb: hemoglobin; NA: no anticoagulation; PLT: platelet; PSM: propensity score matching; PT: prothrombin time; RCA: regional citrate anticoagulation. | ||||||||
| Male | 69 (70.4) | 49 (70) | 20 (71.4) | 0.889 | 33 (78.6) | 16 (76.2) | 17 (81) | > 0.99 |
| Age, years | 53.0 ± 14.5 | 52.5 ± 13.0 | 54.2 ± 17.9 | 0.603 | 53.5 ± 16.7 | 51.5 ± 14.6 | 55.4 ± 18.8 | 0.461 |
| APACHE II score | 28.3 ± 4.5 | 27.9 ± 4.5 | 29.2 ± 4.5 | 0.213 | 28.4 ± 3.2 | 28.8 ± 3.0 | 28.0 ± 3.4 | 0.448 |
| GCS score | 3.0 ± 1.8 | 3.2 ± 2.0 | 2.6 ± 1.2 | 0.146 | 2.8 ± 1.1 | 2.7 ± 1.0 | 2.8 ± 1.3 | 0.791 |
| Mechanical ventilation | 86 (87.8) | 62 (88.6) | 24 (85.7) | 0.738 | 40 (95.2) | 20 (95.2) | 20 (95.2) | > 0.99 |
| Neurologic disease | 0.429 | 0.156 | ||||||
| Traumatic brain injury | 35 (35.7) | 27 (38.6) | 8 (28.6) | 15 (35.7) | 7 (33.3) | 8 (38.1) | ||
| Intracerebral hemorrhage | 39 (39.8) | 25 (35.7) | 14 (50) | 21 (50.0) | 13 (61.9) | 8 (38.1) | ||
| Subarachnoid hemorrhage | 4 (4.1) | 4 (5.7) | 0 (0) | 0 (0) | 0 (0) | 0 (0) | ||
| Other categories | 20 (20.4) | 14 (20) | 6 (21.4) | 6 (14.3) | 1 (4.8) | 5 (23.8) | ||
| Post craniocerebral operation | 74 (75.5) | 55 (78.6) | 19 (67.9) | 0.265 | 30 (71.4) | 15 (71.4) | 15 (71.4) | > 0.99 |
| Comorbidity | ||||||||
| Hypertension | 50 (51.0) | 34 (48.6) | 16 (57.1) | 0.443 | 24 (57.1) | 11 (52.4) | 13 (61.9) | 0.533 |
| Diabetes | 23 (23.5) | 14 (20) | 9 (32.1) | 0.2 | 11 (26.2) | 4 (19) | 7 (33.3) | 0.292 |
| Use of osmotic diuretics | 83 (84.7) | 61 (87.1) | 22 (78.6) | 0.353 | 36 (85.7) | 18 (85.7) | 18 (85.7) | > 0.99 |
| AKI | 70 (71.4) | 46 (65.7) | 24 (85.7) | 0.048 | 33 (78.6) | 16 (76.2) | 17 (81) | > 0.99 |
| AKI stage | 0.003 | 0.616 | ||||||
| AKI stage 1 | 39 (39.8) | 30 (42.9) | 9 (32.1) | 16 (38.1) | 8 (38.1) | 8 (38.1) | ||
| AKI stage 2 | 20 (20.4) | 13 (18.6) | 7 (25.0) | 10 (23.8) | 6 (28.6) | 4 (19.0) | ||
| AKI stage 3 | 11 (11.2) | 3 (4.3) | 8 (28.6) | 7 (16.7) | 2 (9.5) | 5 (23.8) | ||
| Urine volume, mL | 3,415.1 ± 1,776.0 | 3,514.0 ± 1,715.4 | 3,167.8 ± 1,929.5 | 0.386 | 3,502.2 ± 1,684.6 | 3,597.8 ± 1,593.8 | 3,406.6 ± 1,805.1 | 0.718 |
| Serum sodium, mmol/L | 171.7 ± 8.9 | 172.3 ± 9.4 | 170.4 ± 7.7 | 0.349 | 171.2 ± 8.4 | 170.2 ± 9.3 | 172.1 ± 7.6 | 0.472 |
| Total calcium, mmol/L, | 2.3 ± 0.2 | 2.3 ± 0.2 | 2.3 ± 0.2 | 0.304 | 2.3 ± 0.2 | 2.4 ± 0.3 | 2.3 ± 0.2 | 0.523 |
| Serum creatinine, µmol/L, | 176.3 ± 127.2 | 147.8 ± 95.7 | 247.8 ± 165.2 | < 0.001 | 205.3 ± 132.4 | 195.2 ± 113.1 | 215.3 ± 151.5 | 0.629 |
| Serum urea, mmol/L | 17.4 ± 11.3 | 16.5 ± 11.3 | 19.8 ± 11.1 | 0.191 | 20.3 ± 11.2 | 20.5 ± 9.8 | 20.1 ± 12.7 | 0.894 |
| Hb, g/L | 107.1 ± 23.5 | 104.8 ± 24.0 | 112.6 ± 21.7 | 0.138 | 111.4 ± 23.3 | 112.2 ± 25.6 | 110.6 ± 21.4 | 0.83 |
| PLT count, × 109/L | 139.7 ± 80.4 | 144.8 ± 79.1 | 126.9 ± 83.6 | 0.321 | 142.0 ± 80.5 | 146.6 ± 71.3 | 137.3 ± 90.4 | 0.715 |
| PT (s) | 14.9 ± 3.2 | 15.0 ± 3.5 | 14.8 ± 2.4 | 0.768 | 14.6 ± 1.7 | 14.8 ± 1.5 | 14.4 ± 1.9 | 0.484 |
| aPTT (s) | 30.6 ± 8.2 | 30.5 ± 8.7 | 30.6 ± 7.1 | 0.976 | 30.3 ± 6.0 | 31.2 ± 6.0 | 29.5 ± 5.9 | 0.369 |
| Serum ALB, g/L | 34.6 ± 5.9 | 34.0 ± 6.1 | 36.0 ± 5.1 | 0.133 | 36.5 ± 6.2 | 36.1 ± 7.3 | 37.0 ± 5.1 | 0.674 |
| Serum total bilirubin, mmol/L | 16.6 ± 13.3 | 15.8 ± 13.6 | 18.6 ± 12.5 | 0.357 | 16.4 ± 10.1 | 15.8 ± 10.5 | 16.9 ± 10.0 | 0.724 |
| Variables | Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|---|
| Total (n = 98) | RCA (n = 70) | NA (n = 28) | P value | Total (n = 42) | RCA (n = 21) | NA (n = 21) | P value | |
| CRRT: continuous renal replacement therapy; NA: no anticoagulation; PSM: propensity score matching; RCA: regional citrate anticoagulation. | ||||||||
| Post CRRT serum sodium, mmol/L | 148.6 ± 7.0 | 147.9 ± 6.8 | 150.5 ± 7.2 | 0.094 | 148.8 ± 7.1 | 146.8 ± 6.1 | 150.8 ± 7.6 | 0.068 |
| Mean hypernatremia correction rates, mmol/L/h | 0.5 ± 0.1 | 0.5 ± 0.1 | 0.5 ± 0.1 | 0.587 | 0.5 ± 0.1 | 0.5 ± 0.2 | 0.5 ± 0.1 | 0.613 |
| CRRT duration, h | 49.2 ± 22.5 | 52.6 ± 22.2 | 40.8 ± 21.2 | 0.017 | 45.9 ± 19.7 | 49.2 ± 17.6 | 42.7 ± 21.5 | 0.291 |
| Adverse events rate, n (%) | ||||||||
| Bleeding | 14 (14.3) | 6 (8.6) | 8 (28.6) | 0.021 | 5 (11.9) | 0 (0) | 5 (23.8) | 0.048 |
| Frequent filter clotting | 17 (17.3) | 0 (0) | 17 (60.7) | < 0.001 | 12 (28.6) | 0 (0) | 12 (57.1) | < 0.001 |
| Metabolic acidosis | 14 (14.3) | 9 (12.9) | 5 (17.9) | 0.534 | 5 (11.9) | 2 (9.5) | 3 (14.3) | 1 |
| Metabolic alkalosis | 13 (13.3) | 7 (10) | 6 (21.4) | 0.186 | 7 (16.7) | 2 (9.5) | 5 (23.8) | 0.41 |
| Hypocalcemia | 5 (5.1) | 2 (2.9) | 3 (10.7) | 0.139 | 2 (4.8) | 1 (4.8) | 1 (4.8) | 1 |
| Citrate accumulation | 6 (6.1) | 6 (8.6) | 0 (0) | 0.178 | 1 (2.4) | 1 (4.8) | 0 (0) | 1 |
| Group | Time | Total calcium (mmol/L) | Serum creatinine (µmol/L) | Serum urea (mmol/L) | Hb (g/L) | PLT count (× 109/L) | PT (s) | aPTT (s) | Serum ALB (mmol/L) | Serum total bilirubin (mmol/L) |
|---|---|---|---|---|---|---|---|---|---|---|
| aCompared with the NA group before CRRT, P < 0.05. bCompared with in this group before CRRT, P < 0.05. ALB: albumin; aPTT: activated partial thromboplastin time; CRRT: continuous renal replacement therapy; Hb: hemoglobin; NA: no anticoagulation; PLT: platelet; PT: prothrombin time; RCA: regional citrate anticoagulation. | ||||||||||
| RCA (n = 70) | Before CRRT | 2.3 ± 0.2 | 147.8 ± 95.7a | 16.5 ± 11.3 | 104.8 ± 24.0 | 144.8 ± 79.1 | 15.0 ± 3.5 | 30.5 ± 8.7 | 34.0 ± 6.1 | 15.8 ± 13.6 |
| After CRRT | 2.5 ± 0.2b | 100.1 ± 58.2b | 12.1 ± 7.1b | 104.1 ± 21.5 | 104.6 ± 72.1b | 15.1 ± 3.2 | 32.3 ± 5.0b | 36.8 ± 5.1b | 18.4 ± 7.5b | |
| Difference | −0.1 ± 0.3 | 16.5 ± 11.3 | 4.4 ± 8.2 | 0.8 ± 15.7 | 40.2 ± 60.6 | 0.0 ± 3.7 | −1.8 ± 8.4 | −2.8 ± 6.4 | −2.6 ± 14.0 | |
| NA (n = 28) | Before CRRT | 2.3 ± 0.2 | 247.8 ± 165.2 | 19.8 ± 11.1 | 112.6 ± 21.7 | 126.9 ± 83.6 | 14.8 ± 2.4 | 30.6 ± 7.1 | 36.0 ± 5.1 | 18.6 ± 12.5 |
| After CRRT | 2.4 ± 0.2b | 166.8 ± 100.5b | 14.9 ± 6.5b | 106.9 ± 22.8 | 84.1 ± 54.1b | 14.6 ± 2.4 | 33.3 ± 7.2b | 36.2 ± 6.1 | 23.6 ± 14.2b | |
| Difference | −0.2 ± 0.3 | 81.0 ± 113.5 | 4.9 ± 7.9 | 5.7 ± 21.3 | 42.8± 41.7 | 0.2 ± 2.9 | −2.7 ± 8.0 | −0.2 ± 7.6 | −5.0 ± 12.9 | |
| Group | Time | Total calcium (mmol/L) | Serum creatinine (µmol/L) | Serum urea (mmol/L) | Hb (g/L) | PLT count (× 109/L) | PT (s) | aPTT (s) | Serum ALB (mmol/L) | Serum total bilirubin (mmol/L) |
|---|---|---|---|---|---|---|---|---|---|---|
| bCompared with in this group before CRRT, P < 0.05. ALB: albumin; aPTT: activated partial thromboplastin time; CRRT: continuous renal replacement therapy; Hb: hemoglobin; NA: no anticoagulation; PLT: platelet; PT: prothrombin time; RCA: regional citrate anticoagulation. | ||||||||||
| RCA (n = 21) | Before CRRT | 2.4 ± 0.3 | 195.2 ± 113.1 | 20.5 ± 9.8 | 112.2 ± 25.6 | 146.6 ± 71.3 | 14.8 ± 1.5 | 31.2 ± 6.0 | 36.1 ± 7.3 | 15.8 ± 10.5 |
| After CRRT | 2.5 ± 0.2 | 122.5 ± 72.4b | 14.3 ± 6.3b | 112.1 ± 22.9 | 118.3 ± 90.2b | 15.2 ± 2.2 | 34.8 ± 5.3b | 37.5 ± 4.7 | 19.8 ± 7.3b | |
| Difference | −0.1 ± 0.3 | 72.7 ± 51.1 | 6.1 ± 7.4 | 0.1 ± 11.4 | 28.2 ± 53.0 | −0.5 ± 3.0 | −3.6 ± 6.8 | −1.3 ± 6.2 | −3.9 ± 10.7 | |
| NA (n = 21) | Before CRRT | 2.3 ± 0.2 | 215.3 ± 151.5 | 20.1 ± 12.7 | 110.6 ± 21.4 | 137.3 ± 90.4 | 14.4 ± 1.9 | 29.5 ± 5.9 | 37.0 ± 5.1 | 16.9 ± 10.0 |
| After CRRT | 2.5 ± 0.3 | 134.4 ± 73.6b | 14.1 ± 6.5b | 107.6 ± 21.5 | 88.9 ± 56.6b | 14.6 ± 2.5 | 34.0 ± 8.1b | 37.1 ± 6.2 | 21.8 ± 10.6b | |
| Difference | −0.2 ± 0.3 | 80.9 ± 92.7 | 6.2 ± 6.9 | 3.0 ± 21.3 | 48.5 ± 45.2 | −0.2 ± 2.5 | −4.5 ± 7.4 | −0.2 ± 7.7 | −4.9 ± 11.9 | |
| Variables | Univariate analysis | Multivariable analysis | ||||
|---|---|---|---|---|---|---|
| HR | 95% CI | P value | HR | 95% CI | P value | |
| Note: The multivariable Cox proportional hazards model was constructed by including all variables with a P-value < 0.05 in the univariate analysis (i.e., RCA, hypertension, use of osmotic diuretics, AKI, serum sodium, and serum creatinine). The variance inflation factor (VIF) for each covariate in the final model was < 5, indicating no significant multicollinearity. AKI: acute kidney injury; CI: confidence interval; HR: hazard ratio; RCA: regional citrate anticoagulation. | ||||||
| RCA (yes vs. no) | 0.19 | 0.11–0.31 | < 0.001 | 0.09 | 0.05–0.18 | < 0.001 |
| Hypertension (yes vs. no) | 2.08 | 1.29–3.35 | 0.003 | 2.49 | 1.46–4.26 | 0.001 |
| Use of osmotic diuretics (yes vs. no) | 2.19 | 1.00–4.78 | 0.05 | 3.27 | 1.39–7.67 | 0.007 |
| AKI (yes vs. no) | 2.22 | 1.23–3.98 | 0.008 | 1.36 | 0.69–2.66 | 0.371 |
| Serum sodium | 0.96 | 0.93–0.99 | 0.006 | 0.96 | 0.93–0.99 | 0.013 |
| Serum creatinine | 1.002 | 1.0005–1.0039 | 0.012 | 1.00 | 0.99–1.00 | 0.007 |
| Variables | Before PSM | After PSM | ||||||
|---|---|---|---|---|---|---|---|---|
| Total (n = 98) | RCA (n = 70) | NA (n = 28) | P value | Total (n = 42) | RCA (n = 21) | NA (n = 21) | P value | |
| ICU: intensive care unit; NA: no anticoagulation; PSM: propensity score matching; RCA: regional citrate anticoagulation. | ||||||||
| Days in ICU | 19.5 ± 16.1 | 21.0 ± 17.5 | 15.7 ± 11.7 | 0.146 | 15.9 ± 10.6 | 16.4 ± 11.5 | 15.3 ± 10.0 | 0.732 |
| Costs in hospital, yuan | 229,919.7 ± 213,678.5 | 258,761.0 ± 240,991.8 | 157,816.6 ± 89,807.1 | 0.034 | 192,082.6 ± 138,796.6 | 228,431.1 ± 168,930.5 | 155,734.1 ± 90,444.3 | 0.09 |
| In-hospital mortality | 18 (18.4) | 10 (14.3) | 8 (28.6) | 0.099 | 9 (21.4) | 2 (9.5) | 7 (33.3) | 0.13 |
| Mortality on 28 days | 63 (64.3) | 42 (60) | 21 (75) | 0.162 | 31 (73.8) | 16 (76.2) | 15 (71.4) | 0.726 |