List the relevant pharmacology of the following drugs when used in ICU to aid the dressing of severe burns: (a) tramadol,  (b) celecoxib and (c) ketamine.

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College Answer

Tramadol is a synthetic non-narcotic analgesic with opioid like effects. It acts centrally to bind with mu receptors and also blocks noradrenaline and serotonin uptake. It is rapidly absorbed orally with high bioavailability. It is cleared by hepatic metabolism and may produce dizziness, somnolence, nausea, constipation, sweating and pruritus similar to opioids, but causes significantly less respiratory depression than morphine.

After an IMI dose, peak effect is achieved in 45 minutes and lasts 4-5 hours. Convulsions and rare anaphylactoid reactions have been described with its use. Overdosage may produce respiratory failure and seizures. Its role in this setting is unclear as yet because of low potency but it may be useful as an adjunct.

Celecoxib is a COX-2 inhibitor and as such has anti-inflammatory, analgesic and anti-pyretic properties. In the absence of COX-1 inhibition, it should have no/little effect on gastrointestinal mucosa or platelet function. Disruption of renal blood flow autoregulation in hypovolaemia and shock is still possible.

NSAIDS have been used in burns to reduce the inflammatory response, but have an uncertain role in dressings due to slow onset (1 hour), low potency, oral preparation and untoward renal effect. Duration of action is 6 – 15 hours. They should not be used in patients with sulfonamide allergy or aspirin/NSAID associated asthma.

Ketamine is a general anaesthetic agent related to the hallucinogen phencyclidine which can be given IV or IM. Despite the tendency to emergence delirium it is a useful agent in this setting because of intense analgesia with maintenance of reflexes and minimal respiratory depression. Duration of action is 2 – 4 hours and it undergoes extensive hepatic metabolism. Dreams and hallucination can be reduced by the concomitant administration of a benzodiazapine.

Discussion

Features

Tramadol

Celecoxib

Ketamine

Class/mechanism

Partial opioid receptor agonist;
Serotonin receptor agonist

NSAID (selctive for COX-2)

Anaesthetic;
NMDA receptor antagonist

Advantages

Synergistic with other analgesics

Less respiratory depression than with other opiates

Low toxicity
Synergy with opioids

Dissociative sedation
Opioid-sparing effect

Disadvantages

Weak opioid effect
Lowers seziure threshold
Slow onset
Interacts with SSRIs

May cause renal impairment
May cause platelet dysfunction
Slow onset
Weak analgesic

Confusion, delirium
Emergeance phenomena
Requires speialist staff to be present

Some mixture of ketamine, tramadol and dexmedetomidine may be the best option.

References

References

 

Zor, Fatih, et al. "Pain relief during dressing changes of major adult burns: ideal analgesic combination with ketamine." Burns 36.4 (2010): 501-505.

 

Norman, Aidan T., and Keith C. Judkins. "Pain in the patient with burns." Continuing Education in Anaesthesia, Critical Care & Pain 4.2 (2004): 57-61.

 

Power, Camillus Kevin. "Burns Injury Pain Management-the evidence or not!."Official publication of the National Academy of Burns-India (2009).