Case 2
| Oral caffeine treatment | |||||
|---|---|---|---|---|---|
| Parameters | Baseline | Day 1 | Day 2 | Day 3 | Day 4 |
| Ventilator mode | SIMV | SIMV | PSV | VM | VM |
| Pi | 8 | 8 | - | - | - |
| PS | 8 | 8 | 8 | - | - |
| PEEP | 5 | 5 | 5 | - | - |
| FiO2 | 0.4 | 0.4 | 0.3 | 0.5 | 0.5 |
| Vent set RR | 14 | 12 | - | - | - |
| Total RR | 14 | 12 | 10 | 15 | 12 |
Daily changes in mechanical ventilator setting and respiratory rate during caffeine treatment (a) Case 1
| Oral caffeine treatment | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Parameters | Baseline | Day 1 | Day 2 | Day 3 | Day 4 | Day 5 | Day 6 | Day 7 | Day 8 | Day 9 | Day 10 | Day 11 | Day 12 | Day 13 |
| Ventilator mode | SIMV | SIMV | PSV | PSV | TM | PSV | TM | PSV | TM | SIMV | TM | TM | TM | TM |
| Pi | 12 | 12 | - | - | - | - | - | - | - | 10 | - | - | - | - |
| PS | 12 | 12 | 12 | 10 | - | 10 | - | 15 | - | 10 | - | - | - | - |
| PEEP | 5 | 5 | 5 | 5 | - | 5 | - | 5 | - | 5 | - | - | - | - |
| FiO2 | 0.3 | 0.3 | 0.3 | 0.3 | 0.28 | 0.3 | 0.28 | 0.3 | 0.28 | 0.3 | 0.28 | 0.28 | 0.28 | 0.28 |
| Vent set RR | 10 | 10 | - | - | - | - | - | - | - | 10 | - | - | - | - |
| Total RR | 11 | 11 | 17 | 19 | 15 | 15 | 26 | 10 | 27 | 13 | 26 | 28 | 32 | 28 |
Respiratory stimulants
| Agent | Pharmacological class | Mechanism of action | Key findings from human study |
|---|---|---|---|
| Almitrine | Chemoreceptor stimulant | A piperazine derivative that increases the slope of respira- tory response to carbon dioxide through its long-lasting stimula- tion of ventilation [18]. | Reversed fentanyl induced respiratory depression [19] Its marketing license was withdrawn in 2013 by the European Medicines Agency due to its association with potentially serious and long-lasting peripheral neuropathy [20] |
| Aminophylline | Phosphodiesterase (PDE) enzyme inhibitor | Inhibits PDE-3 and PDE-4 and results in bronchodilation [8] | Shortened the time to spontaneous ventilation from propofol and remifentanil anesthesia in post-operative patients [21] |
| Buspirone | 5-HT agonist | High affinity for serotonin 5-HT1A and 5-HT2 receptors [8] | No effect on morphine-induced respiratory depression in healthy volunteers [22] |
| CX717 | Ampakine | Stimulates respiration through its action at AMPA receptors [23] | Prevented alfentanil induced respiratory depression without affecting analgesia, albeit an increase in sedation [24] |
| Doxapram | Chemoreceptor stimu- lant | stimulates respiration through its action at K2P channels at type 1 glomus cells of the carotid bodies [25] | Reversed opioids induced respiratory depression as well as shortening of time to spontaneous ventilation after propofol and remifentanil anesthesia [26, 27, 28] Caused an increase in blood pressure [29] and side effects such as anxiety, panic attack and QTc prolongation [30, 31, 32] |
| Esketamine | NMDA receptor antago- nist | Nonselective, noncompetitive NMDA receptor antagonist [8] | Reversed alfentanil induced respiratory depression [33] |
| GAL021 | Calcium-activated po- tassium (BKCa) channel blocker | Inhibits BKCa channels primar- ily working through the carotid body [34] | Reversed alfentanil induced respiratory depression [35,36] |