TABLE 1

Comparison between patients who developed neurotoxicity for which piperacillin causality was suggestive and patients who did not show piperacillin neurotoxicitya

ParameterbResult forc:P valued
Piperacillin neurotoxicity group (n = 23)Rest of cohort (n = 30)
Demographic data and medical history at admission
    Women, %39.123.30.2423
    Age, median yr65 (61.5–71.5)71.5 (64.3–79.5)0.0502
    Wt, median kg87 (68–99)87.5 (78.3–99)0.1778
    BMI, median kg/m229.6 (23.3–32.8)28.4 (25–32.7)0.6416
    History of brain injury (stroke or trauma), %13.000.0760
    History of epilepsy, %8.73.30.5730
    History of alcoholism, %17.413.30.7150
    History of drug abuse, %00
    History of cardiovascular disease, %82.676.70.7379
    History of cancer, %43.4600.2756
    SAPS II, median58 (46–76)54 (42–73)0.4454
Clinical data from day of piperacillin serum measurement
    Fever, %30.4200.5220
    Sepsis, %65.226.70.0006*
    Mechanical ventilation, %60.953.30.7800
    Renal replacement therapy, %26.126.71
    Vasopressive comedications, %82.646.70.0100*
    Potentially neurotoxic comedications, %73.9800.7430
    Hepatic impairment, %30.413.30.1770
Biological data from day of piperacillin serum measurement
    Creatininemia, median μM261 (170–349.5)122 (54–242)0.0169*
    eGFR, median ml/min/1.73 m218 (15–37)50 (12–83)0.0142*
    Proteinemia, median g/liter55 (51–60)55 (42–64)0.7060
    Natremia, median mM139 (137–144)138 (130–141)0.3726
    Calcemia, median mM1.9 (1.8–2)2 (1.8–2.2)0.1368
    Lactatemia, median mM1.6 (1.1–2.4)1.5 (1.1–1.9)0.3528
    CRP, median mg/liter149.6 (103–281.2)144.3 (89.9–190.1)0.1537
    PCT, median μg/liter25 (1.9–35.6)2.48 (2.5–9.45)0.0072*
    pH, median7.39 (7.35–7.47)7.44 (7.39–7.47)0.3173
Piperacillin treatment at initiation time
    Dose, median g/24 h12 (12–12)12 (12–12)0.4866
    Dose normalized to eGFR, median g/24 h/100 ml/min/1.73 m236.4 (16–58.6)28.6 (12.8–52.5)0.5634
Piperacillin treatment on day of piperacillin serum measurement
    Dose, median g/24 h12 (8–12)12 (9–12)0.9207
    Dose normalized to eGFR, median g/24 h/100 ml/min/1.73 m248 (35.3–69.7)22 (14.3–54)0.0111*
    Serum concn, median mg/liter156.9 (95.4–236)91.3 (68.6–126.8)0.0016*
    Time from treatment initiation, median days3 (2–5)3 (2–5)0.7819
    fC/MIC, median9.72 (5.35–15.06)5.4 (3.6–7.9)0.0174*
  • a Patients who developed neurotoxicity for which the piperacillin causality was suggestive are represented by the piperacillin neurotoxicity group, and those who did not show piperacillin neurotoxicity are indicated as the rest of the cohort.

  • b Abbreviations: BMI, body mass index; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; fC/MIC, free concentration of piperacillin over the MIC of the infective pathogen; PCT, procalcitonin; SAPS II, simplified acute physiology score.

  • c Interquartile ranges are shown in parentheses.

  • d *, significant at P <0.05.