Background
Methods/Design
Primary aim
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To develop PK models for the antibiotic, sedative and analgesic study drugs and their relevant metabolites described in Table 1 in patients receiving ECMO.
Sedative and analgesics | Antiviral/antifungal | Antibacterial |
---|---|---|
Morphine | Fluconazole | Ceftriaxone |
Morphine-3 & 6-glucuronide | Caspofungin | Meropenem |
Fentanyl & nor-fentanyl | Voriconazole | Vancomycin |
Midazolam | Oseltamivir | Ciprofloxacin |
1& 4 hydroxy midazolam | Oseltamivir carboxylate | Gentamicin |
Propofol | Piperacillin-tazobactum | |
Dexmedetomidine | Ticarcillin-clavulunate | |
Thiopentone | Linezolid |
Secondary aims
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To assess the adequacy of current antibiotic dosing regimens in patients on ECMO.
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To develop guidelines for antibiotic drug dosing during ECMO.
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To develop ECMO-specific sedation protocols.
Participants
Inclusion criteria
Exclusion criteria
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No consent
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Known allergy to study drug
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Pregnancy
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Serum bilurubin > 150 μmol/L
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Ongoing massive blood transfusion requirement (> 50% blood volume transfused in the previous 8 hours)
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Therapeutic plasma exchange in the preceding 24 hours
Drug administration
Antibiotics
Sedative and analgesic drugs
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Propofol IV (10–200 mg/hr)
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Dexmedetomidine IV (1 mcg/kg bolus and 0.1–1.5 mcg/kg/min)
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Fentanyl IV (50–300 mcg/hour) if morphine is discontinued for clinical reasons
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Thiopentone IV (100–200 mg/hour)*
Sample collection
Blood sampling: antibiotics
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Six-hourly dosing schedule – Blood will be sampled from an existing arterial line at the following times: 0, 15, 30, 45, 60, 90, 120, 180 and 360 minutes.
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Eight or 12-hourly dosing schedule – Blood samples will be collected from an existing arterial line at the following times: 0, 15, 30, 45, 60, 90, 120, 180 and 480 minutes.
Blood sampling: sedatives and analgesics
Urine specimens
Data collection and management
Demographic data
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Age
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Gender
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Weight
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Height
Clinical data
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Admission diagnosis, allergies
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Illness severity scores [Sequential Organ Failure Assessment (SOFA)on the day of PK sampling & Acute Physiology and Chronic Health Evaluation (APACHE III) on admission]
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Use of renal replacement therapy
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Sedation scores (RASS, BIS)
Organ function data
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Serum bilurubin, total protein and albumin concentrations
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Serum creatinine concentrations
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8-hour urinary creatinine clearance
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24 h fluid balance and blood product requirements
ECMO data
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Days of ECMO
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ECMO flows during sampling period
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Type of oxygenator and pump
Study drug dosing data
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Dose, time and frequency
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Time of sampling
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Day of therapy