Table 1.
Physicochemical compatibility of caffeine citrate 20 mg/mL (10 mg/mL caffeine base) with secondary drugs 2-in-1 parenteral nutrition solutions (see Table S2 for details)
| Secondary drug | Test concentration | Diluent | PC | CAF ratio | 95% CI of ratio |
|---|---|---|---|---|---|
| Aciclovir | 5 mg/mL | D5W | Ia | - | - |
| Alprostadil | 20 mcg/mL | NS | C | 99.9 | 98.1–101.7 |
| Amoxicillin | 100 mg/mL | WFI | C | 99.9 | 99.1–100.8 |
| Amphotericin (Fungizone) | 100 mcg/mL | D5W | C | 98.8 | 97.1–100.6 |
| Amphotericin liposomal | 2 mg/mL | D5W | Ib | - | - |
| Ampicillin | 100 mg/mL | WFI | C | 99.8 | 98.9–100.7 |
| Benzylpenicillin | 100 mg/mL | WFI | C | 100.6 | 99.4–101.7 |
| Calcium gluconate | 100 mg/mL | U | C | 99.5 | 98.2–100.9 |
| Cefotaxime | 100 mg/mL | WFI | C | 100.2 | 99.3–101.2 |
| Ciprofloxacin* | 2 mg/mL | U | C | 100.2 | 99.5–100.9 |
| Clonidine | 2 mcg/mL | NS | C | 99.6 | 98.2–101.0 |
| Cloxacillin | 100 mg/mL | WFI | C | 100.1 | 98.2–101.9 |
| Dobutamine | 7.2 mg/mL | NS | C | 100.1 | 99.3–100.9 |
| Dobutamine | 7.2 mg/mL | D5W | C | 100.0 | 98.8–101.3 |
| Dopamine | 7.2 mg/mL | NS | C | 100.0 | 99.4–100.6 |
| Dopamine | 7.2 mg/mL | D5W | C | 100.6 | 99.3–101.8 |
| Dexmedetomidine | 1 mcg/mL | NS | C | 99.7 | 98.4–101.1 |
| Epinephrine | 64 mcg/mL | D5W | C | 100.1 | 99.5–100.7 |
| Fentanyl | 50 mcg/mL | U | C | 99.8 | 98.7–101.0 |
| Flucloxacillin | 50 mg/mL | D5W | C | 99.2 | 96.9–101.5 |
| Fluconazole | 2 mg/mL | U | C | 99.5 | 98.6–100.5 |
| Furosemide | 1 mg/mL | D5W | Ia | - | - |
| Furosemide | 0.2 mg/mL | D5W | Ic | - | - |
| Gentamicin | 10 mg/mL | NS | C | 99.6 | 99.1–100.1 |
| Heparin | 100 units/mL | NS | C | 99.7 | 98.5–100.8 |
| Hydrocortisone | 10 mg/mL | NS | Ia | - | - |
| Hydrocortisone | 1 mg/mL | NS | C | 99.6 | 97.5–101.7 |
| Indometacin | 200 mcg/mL | NS | C | 99.5 | 98.7–100.3 |
| Ibuprofen | 5 mg/mL | NS | Id | - | - |
| Ibuprofen lysine | 4 mg/mL | NS | Id | - | - |
| Insulin | 0.2 units/mL | NS | C | 99.7 | 98.8–100.6 |
| Levetiracetam | 5 mg/mL | NS | C | 99.5 | 99.0–100.0 |
| Linezolid | 2 mg/mL | U | C | 99.9 | 98.8–100.9 |
| Meropenem | 50 mg/mL | NS | C | 98.9 | 97.1–100.8 |
| Metronidazole | 5 mg/mL | U | C | 99.9 | 98.9–101.0 |
| Midazolam | 1 mg/mL | U | C | 99.5 | 97.8–101.3 |
| Milrinone | 400 mcg/mL | D5W | C | 100.2 | 99.7–100.8 |
| Morphine hydrochloride | 200 mcg/mL | D5W | C | 99.8 | 98.4–101.2 |
| Morphine sulfate | 200 mcg/mL | D5W | C | 100.6 | 99.5–101.8 |
| Norepinephrine | 64 mcg/mL | D5W | C | 100.3 | 99.7–101.0 |
| Paracetamol | 10 mg/mL | U | C | 100.2 | 99.3–101.1 |
| Phenobarbitone | 20 mg/mL | WFI | C | 99.8 | 99.0–100.6 |
| Piperacillin/tazobactam | 200 mg/mL | WFI | C | 99.8 | 98.8–100.7 |
| Rifampicin | 6 mg/mL | NS | C | 100.4 | 98.6–102.1 |
| Sodium bicarbonate | 4.2% w/v | D5W | C | 99.4 | 98.9–99.8 |
| Vancomycin | 10 mg/mL | D5W | C | 99.3 | 97.8–100.8 |
| Vecuronium | 1 mg/mL | WFI | C | 99.7 | 99.4–100.1 |
| Parenteral nutrition PN 1 | - | - | C | 99.2 | 97.7–100.8 |
| Parenteral nutrition PN 2 | - | - | C | 100.5 | 99.1–102.0 |
| Parenteral nutrition PN 3 | - | - | C | 99.6 | 98.9–100.2 |
| Parenteral nutrition PN 4 | - | - | C | 99.9 | 98.9–101.0 |
| Parenteral nutrition PN 5 | - | - | C | 100.5 | 99.4–101.6 |
| Parenteral nutrition PN 6 | - | - | C | 99.7 | 98.8–100.6 |
PC physical compatibility, CAF caffeine, C compatible, I incompatible, D5W glucose 5%, WFI water for injection, NS normal saline/ 0.9% sodium chloride, U undiluted
*Ciprofloxacin was also tested at 4 h to obtain a caffeine ratio of 99.6% and a 95% CI of ratio 98.1–101.1%
aA white precipitate appeared 10–15 min after mixing
bA higher opacity observed in the combination samples in comparison to controls
cParticles observed under polarised light after 30 min of mixing
dA milky turbidity appeared immediately after mixing