List the adverse properties of Propofol and Ketamine.
This question was not well answered by many candidates. Candidates included advantages of these sedative / analgesic agents in their answers when they were not asked for in the question. The best approach to answer this question is to use a table listing their potential adverse properties in categories such as pharmaceutical and chemical properties, pharmacodynamic properties in different body systems, and pharmacokinetics.
The common weaknesses observed included the side effects of ketamine, including its side effects on intracranial pressure, myocardial contractility and oxygen consumption, and hallucinations or delirium. Some adverse properties of propofol including bacterial contamination and pain on injection were also not well covered by many candidates.
References: Goodman and Gilman The pharmacological basis of therapeutics 11th edition p350- 352
"This question was not well answered by many candidates" because the term "adverse properties" is so vague that even now, with the advantage of infinite time, an ICU consultant struggles to generate this answer. It appears the college examiners wanted a list of different pharmaceutical, pharmacokinetic and pharmacodynamic properties of both ketamine and propofol which might make them difficult or inconvenient to store, handle, or use clinically. This is perhaps one of the few situations where a table format might not be the best possible option, as most of the "adverse properties" belong to propofol, and the ketamine column is filled with basically very positive statements about ketamine. Lastly, the "adverseness" of a property is context-dependent, as for example some might say that the longer duration of effect with ketamine is a positive thing, as it provides durable analgesia, whereas others might view this as an inconvenience.
|Unfavourable pharmaceutical characteristics|
|Presentation||Oil emulsion - which causes pain on infusion due to venous irritation||Powder for reconstitution, or in saline to achieve isotonicity - painless infusion|
|Storage||Needs to be stored at room temperature.||Stable in storage under a range of conditions|
|Safety||Anaphylaxis is possible to egg lecithin or soy lipid (theoretically).||No animal or plant excipients, less risk of anaphylaxis|
|Contamination||Theoretical risk of bacterial contamination (mitigated by the addition of EDTA excipient)||Minimal risk of contamination|
|Unfavourable pharmacokinetic characteristics|
|Absorption||Inconveniently limited to IV administration||Can be given orally, IV, IM, subcutaneously, buccally, or as a nasal spray|
|Distribution||Widely distributed and highly protein-bound; prolonged context-sensitive half time with infusions||Widely distributed and highly protein-bound; prolonged context-sensitive half time with infusions|
|Effect offset||Rapidly distributed; rapid offset of effect with bolus administration||Slow offset of effect, which may be undesirable|
|Undesirable pharmacodynamic effects|
|Airway||Decreases airway reflexes||Airway reflexes remain intact|
|Respiratory||Decreases respiratory drive and blunts responses to hypoxia and hypercapnia||Maintains intact respiratory drive and intact respiratory reflexes|
|Cardiovascular||Decreases blood pressure and heart rate, decreases organ perfusion; blunts cardiovascular reflexes||Increases heart rate and blood pressure, increases myocardial oxygen demand; maintains intact cardiovascular reflexes|
|Neurological||Decreases CMRO2 and cerebral blood flow||Increases CMRO2 and cerebral blood flow|
|Psychiatric||Free from psychiatric effects||May cause hallucinations and delirium on emergence. On the plus side, may act as an antidepressant in small doses.|
|Splanchnic||Decreases renal and hepatic perfusion||Maintains intact (or increases) renal and hepatic perfusion. May cause nephrotoxicity with chronic use.|
Clements, J. A., W. S. Nimmo, and I. S. Grant. "Bioavailability, pharmacokinetics, and analgesic activity of ketamine in humans." Journal of pharmaceutical sciences 71.5 (1982): 539-542.
Folts, J. D., S. Afonso, and G. G. Rowe. "SYSTEMIC AND CORONARY HAEMODYNAMIC EFFECTS OF KETAMINE IN INTACT ANAESTHETIZED AND UN ANAESTHETIZED DOGS." BJA: British Journal of Anaesthesia 47.6 (1975): 686-694.
Peltoniemi, Marko A., et al. "Ketamine: a review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy." Clinical pharmacokinetics 55.9 (2016): 1059-1077.
Sahinovic, Marko M., Michel MRF Struys, and Anthony R. Absalom. "Clinical pharmacokinetics and pharmacodynamics of propofol." Clinical pharmacokinetics 57.12 (2018): 1539-1558.
James, Roger, and John B. Glen. "Synthesis, biological evaluation, and preliminary structure-activity considerations of a series of alkylphenols as intravenous anesthetic agents." Journal of medicinal chemistry 23.12 (1980): 1350-1357.
Goodchild, C. S., and Juliet M. Serrao. "Propofol-induced cardiovascular depression: science and art." BJA: British Journal of Anaesthesia 115.4 (2015): 641-642.
De Wit, F., et al. "The effect of propofol on haemodynamics: cardiac output, venous return, mean systemic filling pressure, and vascular resistances." British Journal of Anaesthesia 116.6 (2016): 784-789.