Effect of Intravenous Dexamethasone on Postoperative Pain after Spinal Anaesthesia – a Systematic Review with Meta-analysis and Trial Sequential Analysis

Heesen M, Rijs K, Hilber N et al.

Anaesthesia 2019, 74, 1047-56. doi:10.1111/anae.14666

Aim

Investigate the effect of IV dex on post-op analgesia during single shot spinal anaesthesia

• Equivocal evidence so far

Location

Switzerland/Netherlands/Jordan/Germany

Method

• 1133 patients. 17 trials
• High quality of reporting. Low risk of bias.
• Systematic literature search, then conventional meta-analysis (random effects model)
• Contacted authors to clarify details/ascertain morphine doses
• Trial sequential analysis for primary outcome
• Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to rate level of evidence

Eligibility/Inclusion

• Studies comparing dexamethasone with placebo or combination of dexamethasone with another drug compared with other drug alone
• Surgical procedures under single shot spinal or combined spinal-epidural

Primary Outcome

IV morphine in first 24 post-op hours (& equivalents)

Secondary Outcomes

• Time to first analgesic request
• # patients requiring rescue analgesia
• Use of NSAIDS
• Pain score (VAS/NRS)
• Duration of motor block
• Incidence of wound infections & healing complications

Results

9 studies used 8mg dexamethasone.

10mg/4mg in 2 trials each.

0.1mg/kg in 3 trials.

40mg/16mg in 1 trial each.

Data from several trials could not be combined in a meta-analysis

• Different parameters (time of pain score, at rest/movement, unclear information from studies)

Primary outcome – Morphine 24h – (6 studies, 326 patients)

• 01mg in dex group (-5.01 to -3.01mg) I²=0%
  • (not much difference omitting spinal bupivacaine & morphine, or using 40mg as dex dose)
• Risk of bias low
• Trial sequential analysis à sufficient evidence for primary outcome
• Leave-one-out meta-analysis à result not driven by one single trial
• GRADE evaluation à high level of evidence – further studies unlikely to change result

Secondary outcomes

• Longer time to first analgesic request (86min later) – significant – but heterogeneity in this analysis was high I²=93%
• Other secondary outcomes – no significant difference
  • Number of patients requiring rescue analgesia

Discussion

• Previous meta-analysis of IV dex in GA à – 0.82/0.85mg post-op morphine with moderate/high doses of dex respectively
• No other analysis has found such a pronounced effect of dex
• One trial with intrathecal morphine – no significant difference of dex on opioid consumption
• Suggests 8mg of dex as ideal dose

Strengths

• Interesting question
• Publications in last 10 years – contemporary clinical practice
• Easy intervention

Limitations

• Confusing inclusions/exclusions of studies
• High heterogeneity for “time to first analgesic requests”
  • ? Confounding factor of PCA
• VAS scoring timing/at rest/movement
• ? Side effect profile of dex – infrequent reporting wound infection/healing (Cochrane 2018 – single dose does not affect risk of infections, no definite conclusions for delayed wound healing)
• ? Other side effects of dex not mentioned – such as glucose

Conclusion

• High level of evidence that IV dexamethasone improves post-op analgesia after spinal anaesthesia
  • Reduces 24h morphine equivalent consumption
  • Prolonging time to first analgesic request

Discussion during Journal Club

• Noted that there was a mix of surgical procedures in the meta-analysis – should not mix LSCS/obstetrics with other patients. Hernia operations are not that painful so should not mix with operations after which we normally expect a lot more pain.
• What do people give dexamethasone for? Most at JC are giving it for PONV – is it useful for N&V though and is it the correct dose (see previous JC)? Potentially should be using other N&V drugs?
• Does 4mg IV morphine really make that much difference? Would it make a difference to the opioid side effect profile?
• Does it make a difference when the first request of analgesia is? – Perhaps should have looked at overall opioid consumption
• What is the side effect profile of even a single shot of dexamethasone? Does this need to be considered as well as thinking about decreasing opioid consumption?
• At Kingston we use long acting opioids for LSCS spinals, and for #NOF often a nerve block as well, so IV dexamethasone may not add that much to our practice here.

Summary by Dr PY Kuo. Journal Club Meeting 18th July 2019.