Following knee arthroscopy, pain is often moderate to severe—and the addictive nature of opioids for managing this are well documented. Worldwide, there are over one million knee arthroplasties a year in total, with this number set to increase as the population increasingly ages (Gasbjerg et al, 2022). Noting that multimodal pain management is required for the moderate-to-severe pain, this procedure causes postoperatively, researchers explore dexamethasone as an analgesic adjuvant in multimodal pain management following total knee arthroplasty.
The study
In the recently published study, Gasbjerg et al (2022) examined the effects of one and two doses of intravenous dexamethasone in patients post surgery.
The study was randomised, blinded and placebo-controlled, and follow-up was carried out at 90 days. The research took place across five Danish hospitals, from 2018 to 2020, with 485 adult participants all having a total knee arthroscopy. The team used a computer-generated randomised sequence in order to place participants into one of three groups: DX1 (dexamethasone (24 mg) +placebo); DX2 (dexamethasone (24 mg)+dexamethasone (24 mg)); or placebo (placebo+placebo). The intervention was then administered before surgery and 24 hours after surgery. All participants also received paracetamol, ibuprofen and local infiltration analgesia. Morphine was given on prescription and the amounts received by the patients were calculated to look for a change in need that might be associated with the administration of dexamethasone.
The team analysed data from 472 participants (97.3%) for the primary outcome analysis, and median morphine consumptions at 0-48 hours were: DX1 37.9 mg, DX2 35.0 mg, and placebo 43.0 mg. Postoperative pain was therefore associated with a reduction at 24 hours with one dose, and at 48 hours with two doses, of dexamethasone. The overall conclusion was that 2 doses of dexamethasone was able to reduce morphine consumption within 48 hours following a total knee arthroplasty and was also able to reduce postoperative pain.
Opioid analgesics
Currently, the British National Formulary (BNF, 2022a) states that opioid analgesics can be given to patients with moderate-to-severe postoperative pain, with the dose given as soon as possible when the patient can eat and drink, adjusting the dose as soon as possible so that functional recovery can be helped. Morphine if not given orally can be given via patient-controlled analgesia.
The National Institute for Health and Care Excellence (NICE, 2016) recommends a cautious approach when prescribing controlled drugs such as morphine. The benefits should be considered, as well as the risks of prescribing, risk of dependency, overdose and diversion, and all medications currently being taken must be considered carefully, as well as if the patient might be opioid-naïve (NICE, 2016).
Dexamethasone
The BNF (2022b) notes that dexamethasone is currently restricted to various conditions and is not recommended as an adjunct for pain relief. The only situation where dexamethasone is currently licensed for pain is in palliative care, where there is pain secondary to nerve compression (BNF, 2022b).
Systemic cautions advised for the use of dexamethasone include congestive heart failure, diabetes, diverticulitis, epilepsy, glaucoma, hypertension, hyperthyroidism, infection, psychiatric reactions, peptic ulcer, myocardial infarction, steroid-induced psychosis, thromboembolic disorders and ulcerative colitis (BNF, 2022b).
It is either common or very common for someone who has received dexamethasone to have anxiety, abnormal behaviour, cataracts, cognitive impairment, Cushing's syndrome, electrolyte imbalance, fatigue, fluid retention and gastrointestinal discomfort. Headache, impaired healing, hypertension, menstrual irregularities, weight gain, nausea, osteoporosis, psychotic disorder, skin reactions and sleep problems are also common (BNF, 2022b), which is why implementation of the use of this drug is not normally encouraged. The study may show improvements in codeine consumption and reduced pain, but does this outweigh the risks of receiving dexamethasone?
The researchers state that the reduction in morphine consumption of patients receiving dexamethasone corresponds to almost 25%, even with dexamethasone as an adjuvant to three non-opioid analgesic interventions. The authors were careful to point out that there should not be an overemphasis on statistics such as this, given the use of dexamethasone is not always appropriate or deemed safe. Gasjberg et al (2022) gave participants a multimodal non-opioid treatment, and the reduction in morphine use with dexamethasone should therefore be considered in this context.
At 48 hours only the group receiving a second dose of dexamethasone displayed reductions in pain and with morphine use. The differences in morphine use can be used to reference the analgesic efficacy between intervention ad placebo groups, so Gasbjerg et al (2022) state this can be considered as a valid surrogate outcome mirroring patients’ total pain. The benefit of reducing morphine consumption additionally is that adverse effects from morphine are reduced or avoided.
Despite the well-documented history of adverse effects from dexamethasone in the BNF (2022b), Gasbjerg et al (2022) detected no differences in patient-reported adverse events within 0–48 hours between the groups, and found fewer serious adverse events within 90 days for patients who had two doses of dexamethasone rather than one, but the researchers cannot ascertain the reasoning for this. Dexamethasone appeared to reduce postoperative opioid-related adverse effects such as nausea, vomiting, sedation, and dizziness, Gasjberg et al (2022) report, interestingly.
The team was cautious to remind the reader that the benefit the study showed should always be interpreted in light of the known rare but serious adverse events that can happen, as stated earlier.
An earlier study by Zhou et al (2018) showed similar results. Zhou et al (2018) included six randomised controlled trials in their meta-analysis of the use of dexamethasone for pain management in patients following total knee arthroplasty. They observed significant differences between dexamethasone-treated groups and placebo groups regarding postoperative pain scores at 12, 24 and 48 hours following their surgery. They determined that administering dexamethasone could significantly reduce the use of opioids at 12 hours following total knee arthroplasty. However, Zhou et al (2018) stated that no meaningful difference was observed in opioid consumption at 24 and 48 hours following the surgery, and similarly to Gasjberg et al (2022), saw a decreased risk of adverse effects in dexamethasone groups. The authors concluded the use of dexamethasone could therefore result in a reduction in pain following total knee arthroplasty and those adverse events could also be minimised through its use.
Conclusion
Overall, pain management has remained for some time a multimodal method that does not always achieve full pain management and produces significant adverse effects at times. Someone who has too much pain is unlikely to be rehabilitated as quickly, though it is important to get the patient back to good able-bodied movement for mobilising and washing/ dressing as soon as they are functionally capable of doing so. Furthermore, it is often pain that prevents the patient from wanting to fully engage with physiotherapy. If dexamethasone can reduce adverse effects and reduce the use of highly addictive morphine, this appears to be a positive finding; however, in a small group of patients, there will be very severe adverse events—which may not be a risk worth taking. With more research on the subject, more light can be shed on the use of this drug as an adjunct to pain management and the risks can be fully ascertained.