Table 4 Available data on piperacillin pharmacokinetics in continuous renal replacement therapy

Occhipinti and colleagues [28]

N/A

Noncompartmental

10.90 ± 1.17 l/hour/1.73 m²

0.15 ± 0.02

N/A

N/A

N/A

N/A

Arzuaga and colleagues [29]

0.42 ± 0.25

Noncompartmental

3.00 ± 3.22

0.28 ± 0.16

N/R, CrCL <10 ml/minute

Survival N/R, 100 % target attainment

Dose reduction

Small sample size, no residual diuresis and CrCL estimation method reported

0.38 ± 0.37

Noncompartmental

5.44 ± 1.80

0.36 ± 0.27

N/R, CrCL 10 to 50 ml/minute

Survival N/R, 100 % target attainment for MIC < 32 mg/l, 50 % target attainment for MIC > 64 mg/l

Dose reduction

Small sample size, no residual diuresis and CrCL estimation method reported

0.23 ± 0.07

Noncompartmental

15.91 ± 9.13

0.56 ± 0.25

N/R, CrCL >50 ml/minute

Survival N/R, 55.5 % target attainment for MIC < 32 mg/l, 16.6 % target attainment for MIC > 64 mg/l

4.5 g every 4 hours

Small sample size, no residual diuresis and CrCL estimation method reported

van der Werf and colleagues [30]

N/R

Two compartments

2.52 ± 1.38

0.30 ± 0.21

Anuric

77.8 % survival, 100 % target attainment

Dose as for patients with slightly impaired renal function

No report of sieving, no report of MIC (classified as S/R)

Capellier and colleagues [31]

N/R

Noncompartmental

First dose: 4.75 ± 1.42, steady state: 1.49 ± 0.79

First dose: 0.48 ± 0.24, steady state: 0.14 ± 0.07

Mainly anuric, three with residual diuresis between 220 and 400 ml/24 hours

N/R

4.5 g every 12 hours

No CRRT dose, MIC target and outcome reported, some patients with cardiogenic shock

Asín-Prieto and colleagues [32]

0.37 ± 0.25

Two compartments

7.32 (4.21 to 10.86) (bootstrap)

0.59 (0.38 to 0.82) (bootstrap)

Different degrees of renal function, residual diuresis N/R, CrCL 43 ± 34 ml/minute

Survival N/R, target attainment (MIC = 16 mg/l) after simulations: when CrCL >100 ml/minute, 60 % target attainment with high doses (4 g every 4 hours); when CrCL = 50 ml/minute, 93 % target attainment with 4 g every 4 hours, 62 % PTA with 4 g every 6 hours; when CrCL = 10 ml/minute, 96 % target attainment with 4 g every 8 hours

After simulations: when CrCL = 100 ml/minute, CI 16 g every 24 hours; when CrCL = 50 ml/minute, CI 12 g every 24 hours

No report of number of patients by renal function group, no report of residual diuresis, CrCL estimated using Cockroft–Gault method (not validated for critically ill patients)

Bauer and colleagues [33]

N/R

One compartment

3.87 l/hour (IQR: 3.56)

0.38 l/kg (IQR: 0.20)

Oligoanuric (median 38 ml/24 hours, IQR: 157 ml)

50 % survival, 100 % target attainment for MIC = 16 mg/l (total and unbound piperacillin), 83 % target attainment for MIC = 64 mg/l (total piperacillin), and 77 % target attainment (unbound)

>9 g piperacillin/day

Sparse sampling, CVVHDF and CVVHD data analyzed altogether

Mueller and colleagues [34]

0.84 ± 0.21

Noncompartmental

2.82 (1.56 to 13.2)

0.31 ± 0.07

Anuric

Survival N/R, simulations show 87.5 % target attainment with 4.5 g every 12 hours/2.25 g every 8 hours

4.5 g every 12 hours or 2.25 g every 8 hours

No severity score and outcomes reported, no septic shock

Keller and colleagues [35]

0.71 ± 0.21

One compartment

2.83 ± 1.34

0.37 ± 0.05 (for a 70 kg adult, weight N/R)

Anuric

16.7 % survival.

150 % of dose for anuric patients

First-dose kinetics, no severity score, MIC target and outcomes reported

Valtonen and colleagues [50]

N/R

Noncompartmental

5.06 ± 1.68

N/R

133 ± 199

Survival N/R, 33.3 % target attainment

4.5 g every 8 hours

No severity score and Vd reported. No septic shock, not applicable to critically ill patients

N/R

Noncompartmental

5.48 ± 2.11

N/R

151 ± 224

Survival N/R, 33.3 % target attainment

4.5 g every 8 hours

No severity score and Vd reported. No septic shock, not applicable to critically ill patients

N/R

Noncompartmental

3.89 ± 1.23

N/R

109 ± 182

Survival N/R, 33.3 % target attainment

4.5 g every 8 hours

No severity score and Vd reported. No septic shock, not applicable to critically ill patients

Seyler and colleagues [22]

N/R

Noncompartmental

4.9 (0.14 to 26.6) (for a 70 kg adult, weight N/R)

0.44 (0.22 to 1.72)

N/R

Survival N/R, 71 % target attainment

4.5 g every 6 hours loading dose (first 48 hours), dose reduction thereafter

CVVHDF and CVVHF data analyzed altogether. No severity score, weight and residual renal function reported

Varghese and colleagues [38]

0.67 (0.53 to 0.78)

Noncompartmental

5.1 (4.2 to 6.2)

0.42 (0.29 to 0.49)

Five anuric, five oliguric (<0.5 ml/kg/hour for ≥6 hours)

Survival N/R, 100 % target attainment for MIC ≤32 mg/l

4.5 g every 8 hours for susceptible microorganisms (MIC ≤32 mg/l)

No site of infection and survival reported