Ketamine alone versus propofol added to ketamine versus ketamine mixed in propofol for pediatric procedural sedation in emergency departments.

Children present to emergency departments (EDs) with injuries that require painful procedures such as straightening broken bones and suturing cuts. Medicines used for these procedures include midazolam (a sleeping medicine), nitrous oxide (laughing gas), and morphine (pain killer) as well as many others. Ketamine is one medicine that combines pain relief and sedation. Ketamine is very safe and has been used in millions of procedures around the world. Children when they wake up after ketamine may be agitated or feel like vomiting. Ketamine can raise blood pressure and some situations it should not be used. Ketamine is Australia’s preferred sedative for children in EDs. Perhaps we can improve on ketamine by using different dosing methods or mixing with other medicines.
Propofol is another medicine used to deeply sedate children. In large amounts it will interfere with breathing and lower blood pressure, so it needs to be given in the right place and at the right time. Propofol’s main advantage is that it is much faster to work than ketamine and its effects wear off very fast. Interestingly when propofol is given with ketamine they may balance each other’s side effects; keeping blood pressure even, providing relaxation, reducing vomiting. Since propofol recovery is faster than ketamine, children may wake up sooner.
Emergency doctors have been mixing ketamine and propofol together and calling this combination “ketofol” and find it very effective in adults. Some give ketamine and then propofol, although how much is required is not clear. A number of emergency doctors prefer to give ketamine alone and treat side effects if they occur.

Pharmacokinetic Pharmacodynamics Understanding for Fentanyl Intra-Nasal for children in pain or during painful procedures: pilot study.

Fentanyl is a powerful morphine-like pain reliever. It may be given to children using a puffer (mucosal atomiser) device into the nose. This needle-free method of strong pain relief is gaining popularity in emergency departments. Intranasal fentanyl could also be used for painful procedures that currently receive very little pain relief. Examples include a meningitis test (lumbar puncture), urinary catheter for urine infections (urinary catheter), or placing a tube from nose to the stomach (nasogastric). Randomized controlled trials are required to confirm and quantify the benefit. These trials will also facilitate cost effectiveness analyses and add to safety data. Published research will facilitate practice change by making people aware of this tolerable, probably effective, and most likely cost-effective intervention.

For fentanyl the best dose or concentration to give nasally is unclear, and we have little information for very young children. Fentanyl’s effect is related to concentration achieved at the target organ (brain), which is dependant upon dose, delivery method, age, sex, time of procedure, absorption and each individuals ability to handle the medication (determined by genetics). The method to determine this information in children is using a population pharmacokinetic pharmacodynamic approach (population PKPD), recommended by the US Food and Drug Administration (FDA). Once the PKPD data has been collected, modelling may be performed to estimate optimal dose, concentration and timing.

The PUFFIN studies include randomised controlled trials, quality assurance projects and drug studies. Each study has its own goals but is designed so that results of may be combined using population PKPD. The pilot study will study 10 children and establish laboratory assays, test the feasibility of data collection and validity of pain measurement. Once the pilot is complete, further funding will be sought.