- Prevention of PONV
- Most effective if given at the start of anaethesia
- Increased efficacy if used as part of a multi-modal strategy
- Not effective once there is established PONV
- Low dose as effective as higher doses
- Single dose not associated with common side effects of chronic steroid use
- Prolong the duration of analgesia from regional and neuraxial techniques
- Adjunctive treatment of bacterial meningitis: 10mg Q6H for 4 days
- Reduction in oedema (airway, cerebral) e.g. 3.3mg TDS-QDS
- COVID-19 requiring oxygen therapy: 6mg OD for 10 days
- Replacement therapy in glucocorticoid deficient states or sick day rules
- Reduction of peri-/neo-natal morbidity & mortality in established preterm labour or PPROM
- Immunosuppression e.g. IBD
- Chemotherapy in certain cancers e.g. lymphomas
Dexamethasone
Dexamethasone
- Dexamethasone is a synthetic corticosteroid with primarily glucocorticoid properties
Presentation
- 2mg tablets
- 3.3mg/ml clear colourless solution stored in glass vials at room temperature for IV use
- Topical creams
- Mechanism of action for PONV prophylaxis not completely understood, but thought to arise from non-genomic and genomic anti-inflammatory actions
- Mechanisms include:
- Inhibition of arachidonic acid pathways (i.e. prostaglandin antagonism) reduces GI tract 5-HT secretion
- Reduced bradykinin concentrations in tissues
- Reduced spinal cord nociceptive processing
- Stabilisation of neuronal tissues
- Suppression of neuropeptide release (CGRP, substance P) from nerve endings after tissue injury
Absorption
- Peak plasma levels within 5 mins
- Effects take 1-2hrs to manifest
Distribution
- 77% protein bound
Metabolism
- Slow hepatic metabolism
- Excretion mainly renal as unconjugated steroids
- Biologic half life up to 72hrs
Excretion
- Plasma half-life largely irrelevant as effects outlast plasma levels
- Duration of action 36-72hrs
Cardiovascular
- Positive effect on myocardial contractility
- Can increase vasomotor tone and effect of vasopressor drugs by increasing number of ɑ1 and β-adrenoreceptors
- Prevent oedema formation by reducing capillary wall permeability
Neurological
- Increase CNS excitability as their absence can cause lethargy, apathy, depression, irritability
- May cause insomnia and hyperexcitability, particularly in the elderly
- No significant difference in post-operative delirium or post-operative cognitive dysfunction when dexamethasone used
- Improved QoR-40 scores
- Analgesic effects
- Appears to confer a small analgesic benefit in the perioperative period
- An 8mg (6.6mg IV) dose was associated with a statistically significantly increased risk of persistent wound pain at 6 months BJA, 2023
- Increased duration of short-term analgesia from regional blockade, predominantly with upper limb blocks (Cochrane, 2017)
- Prolonged duration of sensory block with reduced pain intensity at 24hrs, but not 48hrs
- Effect seen regardless of whether dexamethasone given IV or perineurally
Renal
- Increases urinary calcium excretion
- Increases GFR
- Minimal mineralocorticoid activities
Gastrointestinal
- Reduces incidence and severity of PONV and need for additional anti-emetics
- May not, however, decrease risk of 'clinically significant' PONV, a patient-reported outcome reflecting patient experience
- Risk of peptic ulcer disease in chronic use
- Reduces GI absorption of calcium
- Single dose not associated with common side effects of chronic steroid use
Metabolic
- Effect on glycaemic control (PADDAG Trial, 2021)
- A single 4-8mg dose does not induce greater hyperglycaemia compared with placebo for nondiabetic and well controlled diabetic patients
- The effect on blood sugar appears proportional to pre-existing diabetic control based on HbA1c levels
- Gluconeogenesis and increased peripheral uptake of glucose
- Lipolysis
- Inhibit conversion of amino acids to proteins causing a negative nitrogen balance
Other
- Concerns over impairment of wound healing, although the PADDI Trial found a single perioperative dose did not increase wound infection at 30 days vs. placebo
- Concerns over cancer recurrence
- High-doses can reduce the adaptive immune response for up to 48hrs
- Acute withdrawal of long-term use can cause Cushing's disease