Monitoring of Polymyxin B Blood Concentrations and PK/PD Studies in Critically Ill Patients with Severe Infection Undergoing Continuous Renal Replacement Therapy

OBJECTIVE To analyze the blood concentrations and efficacy of polymyxin B in patients undergoing continuous renal replacement therapy(CRRT) and those not undergoing CRRT, to assess the impact of CRRT on the clearance of polymyxin B, and to provide a reference for the rational use of polymyxin B in clinical practice.

METHODS A prospective study design was employed to investigate the plasma concentrations of polymyxin B(including trough concentration, peak concentration, 6 h concentration, and 10 h concentration) in 68 critically ill patients(16 in the CRRT group and 52 in the non-CRRT group) following 48 h of intravenous polymyxin B infusion. Clinical data were collected for both groups, including gender, age, weight, serum creatinine, albumin, infection type, bacteriological status, etc., and conducted intergroup difference tests to assess the impact of CRRT on polymyxin B blood concentrations and explore the relationship between blood concentrations and clinical efficacy and adverse reactions.

RESULTS The CRRT group had AUC_{0-24 h}, C_min, C_max, C₆, and C₁₀ values of (72.85±26.02)mg·h·L⁻¹, (1.67±0.86)mg·L⁻¹, (6.22±2.64)mg·L⁻¹, (2.45±0.94)mg·L⁻¹, (1.89±1.24)mg·L⁻¹; in the non-CRRT group, the AUC_{0-24 h}, C_min, C_max, C₆, and C₁₀ values were(77.99±37.11)mg·h·L⁻¹, (1.75±1.35)mg·L⁻¹, (6.26±2.72)mg·L⁻¹, (2.43±1.19)mg·L⁻¹, and (1.79±1.17)mg·L⁻¹, respectively. There were no statistically significant differences between the two groups in terms of C_min, C_max, C₆, C₁₀, and AUC_{0-24 h}. In terms of clinical efficacy, the proportions of patients in the ineffective and effective groups of the non-CRRT group with polymyxin B AUC_{0-24 h} <50 mg·h·L⁻¹ were 17.4% and 27.6%, respectively; they were 60.9% and 44.8% while AUC_{0-24 h}were in 50–100 mg·h·L⁻¹, respectively; and they were 21.7% and 27.6% while AUC_{0-24 h}≥100 mg·h·L⁻¹, respectively, with no statistically significant difference. In the CRRT group, the proportions of patients in the ineffective and effective groups with polymyxin B AUC_{0-24 h} <50 mg·h·L⁻¹ were 11.1% and 14.3%, respectively; there were 77.8% and 71.4% while AUC_{0-24 h}were in 50–100 mg·h·L⁻¹, respectively; and they were 11.1% and 14.3% while AUC_{0-24 h}≥100 mg·h·L⁻¹, respectively. The distribution proportions were similar, and there was no statistically significant difference between the two groups. Adverse reactions: among 68 patients, 8 cases of adverse reactions occurred, all in the non-CRRT group: 5 cases of skin pigmentation reactions, 2 cases of vomiting, and 1 case of diarrhea. The incidence of acute kidney injury in the non-CRRT group was 32.69%. There was a statistically significant difference in AUC_{0-24 h} between patients with acute kidney injury and those without(P<0.05).

CONCLUSION CRRT does not reduce the blood concentration of polymyxin B. The incidence of acute kidney injury is higher in the non-CRRT group and is associated with AUC_{0-24 h}. Blood concentration monitoring should be performed when using polymyxin B to improve clinical efficacy, reduce renal toxicity or reduce the incidence of adverse reactions.