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
Journal website https://jocmr.elmerjournals.com

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

Figure 1.
Figure 1. Flow chart of enrollment. Included patients (n = 98) were divided into two groups: regional citrate anticoagulation (RCA) groups (n = 70) and no anticoagulation (NA) groups (n = 28). A 1:1 propensity score matching (PSM) was performed to create two balanced groups: “NA group” and “RCA group,” each with n = 21 patients.
Figure 2.
Figure 2. Kaplan-Meier curve shows the filter lifespan of the first filter of the regional citrate anticoagulation (RCA) group and no anticoagulation (NA) group in the original cohort (a) and the matched cohort (b). The Kaplan-Meier survival curves demonstrated significant differences in first filter lifespan between the two anticoagulation groups. The overall median filter survival time was 39.0 h (95% CI, 34.1–43.9). Median filter lifespan was 22.5 h in NA group (95% CI 19.9–25.1). Median lifespan was significantly longer at 43.5 h in RCA group (95% CI, 39.8–47.2) (a). Kaplan-Meier survival curves after matching. The first filter lifespan was considerably longer in the RCA group compared to the NA group (P < 0.001) (b). 95% CI: 95% confidence interval.
Figure 3.
Figure 3. Multivariable Cox proportional risk model regression analysis affecting the lifespan of the first filter. Regional citrate anticoagulation (RCA) remained a significant independent predictor of prolonged first filter lifespan after adjustment for covariates (HR = 0.09, 95% CI, 0.05−0.18). 95% CI: 95% confidence interval; HR: hazard ratio.

Tables

Table 1. Baseline Characteristics of Patients Before and After PSM
 
VariablesBefore PSMAfter PSM
Total (n = 98)RCA (n = 70)NA (n = 28)PTotal (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.
Male69 (70.4)49 (70)20 (71.4)0.88933 (78.6)16 (76.2)17 (81)> 0.99
Age, years53.0 ± 14.552.5 ± 13.054.2 ± 17.90.60353.5 ± 16.751.5 ± 14.655.4 ± 18.80.461
APACHE II score28.3 ± 4.527.9 ± 4.529.2 ± 4.50.21328.4 ± 3.228.8 ± 3.028.0 ± 3.40.448
GCS score3.0 ± 1.83.2 ± 2.02.6 ± 1.20.1462.8 ± 1.12.7 ± 1.02.8 ± 1.30.791
Mechanical ventilation86 (87.8)62 (88.6)24 (85.7)0.73840 (95.2)20 (95.2)20 (95.2)> 0.99
Neurologic disease0.4290.156
  Traumatic brain injury35 (35.7)27 (38.6)8 (28.6)15 (35.7)7 (33.3)8 (38.1)
  Intracerebral hemorrhage39 (39.8)25 (35.7)14 (50)21 (50.0)13 (61.9)8 (38.1)
  Subarachnoid hemorrhage4 (4.1)4 (5.7)0 (0)0 (0)0 (0)0 (0)
  Other categories20 (20.4)14 (20)6 (21.4)6 (14.3)1 (4.8)5 (23.8)
Post craniocerebral operation74 (75.5)55 (78.6)19 (67.9)0.26530 (71.4)15 (71.4)15 (71.4)> 0.99
Comorbidity
  Hypertension50 (51.0)34 (48.6)16 (57.1)0.44324 (57.1)11 (52.4)13 (61.9)0.533
  Diabetes23 (23.5)14 (20)9 (32.1)0.211 (26.2)4 (19)7 (33.3)0.292
Use of osmotic diuretics83 (84.7)61 (87.1)22 (78.6)0.35336 (85.7)18 (85.7)18 (85.7)> 0.99
AKI70 (71.4)46 (65.7)24 (85.7)0.04833 (78.6)16 (76.2)17 (81)> 0.99
AKI stage0.0030.616
  AKI stage 139 (39.8)30 (42.9)9 (32.1)16 (38.1)8 (38.1)8 (38.1)
  AKI stage 220 (20.4)13 (18.6)7 (25.0)10 (23.8)6 (28.6)4 (19.0)
  AKI stage 311 (11.2)3 (4.3)8 (28.6)7 (16.7)2 (9.5)5 (23.8)
Urine volume, mL3,415.1 ± 1,776.03,514.0 ± 1,715.43,167.8 ± 1,929.50.3863,502.2 ± 1,684.63,597.8 ± 1,593.83,406.6 ± 1,805.10.718
Serum sodium, mmol/L171.7 ± 8.9172.3 ± 9.4170.4 ± 7.70.349171.2 ± 8.4170.2 ± 9.3172.1 ± 7.60.472
Total calcium, mmol/L,2.3 ± 0.22.3 ± 0.22.3 ± 0.20.3042.3 ± 0.22.4 ± 0.32.3 ± 0.20.523
Serum creatinine, µmol/L,176.3 ± 127.2147.8 ± 95.7247.8 ± 165.2< 0.001205.3 ± 132.4195.2 ± 113.1215.3 ± 151.50.629
Serum urea, mmol/L17.4 ± 11.316.5 ± 11.319.8 ± 11.10.19120.3 ± 11.220.5 ± 9.820.1 ± 12.70.894
Hb, g/L107.1 ± 23.5104.8 ± 24.0112.6 ± 21.70.138111.4 ± 23.3112.2 ± 25.6110.6 ± 21.40.83
PLT count, × 109/L139.7 ± 80.4144.8 ± 79.1126.9 ± 83.60.321142.0 ± 80.5146.6 ± 71.3137.3 ± 90.40.715
PT (s)14.9 ± 3.215.0 ± 3.514.8 ± 2.40.76814.6 ± 1.714.8 ± 1.514.4 ± 1.90.484
aPTT (s)30.6 ± 8.230.5 ± 8.730.6 ± 7.10.97630.3 ± 6.031.2 ± 6.029.5 ± 5.90.369
Serum ALB, g/L34.6 ± 5.934.0 ± 6.136.0 ± 5.10.13336.5 ± 6.236.1 ± 7.337.0 ± 5.10.674
Serum total bilirubin, mmol/L16.6 ± 13.315.8 ± 13.618.6 ± 12.50.35716.4 ± 10.115.8 ± 10.516.9 ± 10.00.724

 

Table 2. Outcomes of Serum Sodium Reduction Rate and Adverse Events
 
VariablesBefore PSMAfter PSM
Total (n = 98)RCA (n = 70)NA (n = 28)P valueTotal (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/L148.6 ± 7.0147.9 ± 6.8150.5 ± 7.20.094148.8 ± 7.1146.8 ± 6.1150.8 ± 7.60.068
Mean hypernatremia correction rates, mmol/L/h0.5 ± 0.10.5 ± 0.10.5 ± 0.10.5870.5 ± 0.10.5 ± 0.20.5 ± 0.10.613
CRRT duration, h49.2 ± 22.552.6 ± 22.240.8 ± 21.20.01745.9 ± 19.749.2 ± 17.642.7 ± 21.50.291
Adverse events rate, n (%)
  Bleeding14 (14.3)6 (8.6)8 (28.6)0.0215 (11.9)0 (0)5 (23.8)0.048
  Frequent filter clotting17 (17.3)0 (0)17 (60.7)< 0.00112 (28.6)0 (0)12 (57.1)< 0.001
  Metabolic acidosis14 (14.3)9 (12.9)5 (17.9)0.5345 (11.9)2 (9.5)3 (14.3)1
  Metabolic alkalosis13 (13.3)7 (10)6 (21.4)0.1867 (16.7)2 (9.5)5 (23.8)0.41
  Hypocalcemia5 (5.1)2 (2.9)3 (10.7)0.1392 (4.8)1 (4.8)1 (4.8)1
  Citrate accumulation6 (6.1)6 (8.6)0 (0)0.1781 (2.4)1 (4.8)0 (0)1

 

Table 3. Comparison of Laboratory Indicators Before and After CRRT (Original Cohort)
 
GroupTimeTotal 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 CRRT2.3 ± 0.2147.8 ± 95.7a16.5 ± 11.3104.8 ± 24.0144.8 ± 79.115.0 ± 3.530.5 ± 8.734.0 ± 6.115.8 ± 13.6
After CRRT2.5 ± 0.2b100.1 ± 58.2b12.1 ± 7.1b104.1 ± 21.5104.6 ± 72.1b15.1 ± 3.232.3 ± 5.0b36.8 ± 5.1b18.4 ± 7.5b
Difference−0.1 ± 0.316.5 ± 11.34.4 ± 8.20.8 ± 15.740.2 ± 60.60.0 ± 3.7−1.8 ± 8.4−2.8 ± 6.4−2.6 ± 14.0
NA (n = 28)Before CRRT2.3 ± 0.2247.8 ± 165.219.8 ± 11.1112.6 ± 21.7126.9 ± 83.614.8 ± 2.430.6 ± 7.136.0 ± 5.118.6 ± 12.5
After CRRT2.4 ± 0.2b166.8 ± 100.5b14.9 ± 6.5b106.9 ± 22.884.1 ± 54.1b14.6 ± 2.433.3 ± 7.2b36.2 ± 6.123.6 ± 14.2b
Difference−0.2 ± 0.381.0 ± 113.54.9 ± 7.95.7 ± 21.342.8± 41.70.2 ± 2.9−2.7 ± 8.0−0.2 ± 7.6−5.0 ± 12.9

 

Table 4. Comparison of Laboratory Indicators Before and After CRRT (Matched Cohort)
 
GroupTimeTotal 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 CRRT2.4 ± 0.3195.2 ± 113.120.5 ± 9.8112.2 ± 25.6146.6 ± 71.314.8 ± 1.531.2 ± 6.036.1 ± 7.315.8 ± 10.5
After CRRT2.5 ± 0.2122.5 ± 72.4b14.3 ± 6.3b112.1 ± 22.9118.3 ± 90.2b15.2 ± 2.234.8 ± 5.3b37.5 ± 4.719.8 ± 7.3b
Difference−0.1 ± 0.372.7 ± 51.16.1 ± 7.40.1 ± 11.428.2 ± 53.0−0.5 ± 3.0−3.6 ± 6.8−1.3 ± 6.2−3.9 ± 10.7
NA (n = 21)Before CRRT2.3 ± 0.2215.3 ± 151.520.1 ± 12.7110.6 ± 21.4137.3 ± 90.414.4 ± 1.929.5 ± 5.937.0 ± 5.116.9 ± 10.0
After CRRT2.5 ± 0.3134.4 ± 73.6b14.1 ± 6.5b107.6 ± 21.588.9 ± 56.6b14.6 ± 2.534.0 ± 8.1b37.1 ± 6.221.8 ± 10.6b
Difference−0.2 ± 0.380.9 ± 92.76.2 ± 6.93.0 ± 21.348.5 ± 45.2−0.2 ± 2.5−4.5 ± 7.4−0.2 ± 7.7−4.9 ± 11.9

 

Table 5. Univariate and Multivariable Cox Regression Analyses of the Risk Factors of the First Filter Lifespan (Original Cohort)
 
VariablesUnivariate analysisMultivariable analysis
HR95% CIP valueHR95% CIP 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)0.190.11–0.31< 0.0010.090.05–0.18< 0.001
Hypertension (yes vs. no)2.081.29–3.350.0032.491.46–4.260.001
Use of osmotic diuretics (yes vs. no)2.191.00–4.780.053.271.39–7.670.007
AKI (yes vs. no)2.221.23–3.980.0081.360.69–2.660.371
Serum sodium0.960.93–0.990.0060.960.93–0.990.013
Serum creatinine1.0021.0005–1.00390.0121.000.99–1.000.007

 

Table 6. Comparison of Hospitalization Before and After PSM
 
VariablesBefore PSMAfter PSM
Total (n = 98)RCA (n = 70)NA (n = 28)P valueTotal (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 ICU19.5 ± 16.121.0 ± 17.515.7 ± 11.70.14615.9 ± 10.616.4 ± 11.515.3 ± 10.00.732
Costs in hospital, yuan229,919.7 ± 213,678.5258,761.0 ± 240,991.8157,816.6 ± 89,807.10.034192,082.6 ± 138,796.6228,431.1 ± 168,930.5155,734.1 ± 90,444.30.09
In-hospital mortality18 (18.4)10 (14.3)8 (28.6)0.0999 (21.4)2 (9.5)7 (33.3)0.13
Mortality on 28 days63 (64.3)42 (60)21 (75)0.16231 (73.8)16 (76.2)15 (71.4)0.726