The initially planned sample size was 90 in total with drop-outs taken into consideration. However, this study was terminated prematurely due to the COVID-19 outbreak, which suspended all clinical trials and elective operations. Yet given a 0% drop-out rate, the minimal target sample size of 60 was still reached without compromising the power of the study.

In general, the NRS scores (both at rest and upon movement) and the cumulative morphine consumptions were low in both groups. None of the patients requested the administration of intramuscular morphine as rescue analgesics. These features reflected the efficacy of the standard perioperative analgesic regime used and might explain the low incidence of PONV and dizziness observed.

Of the two groups, the Lidocaine-group showed lower NRS at rest (POD 1 am & pm, POD 2 pm) and upon movement (POD 1 am & pm, POD 2 pm). The Lidocaine-group also demonstrated a longer walking distance on an average of 5metres on both POD1 and POD2.Although no statistically significant differences were observed for these outcomes individually, they may have cumulatively contributed to a statistically significant shorter hospital LOS of 1 day in the Lidocaine-group.

It has been shown that lidocaine exhibits a dose-dependent analgesic effect. In small doses (2 µg/ml), lidocaine inhibits ectopic impulse generation in peripheral nerves that are chronically injured; in moderate doses (5 µg/ml), lidocaine suppresses central sensitization and neuronal hyperexcitability; and in large doses (10 µg/ml), lidocaine exhibits general analgesic effects [12].

However, the routine use of LIA intraoperatively, which contained 300 mg of ropivacaine, significantly restricted the dose of lidocaine that could be administered without the concerns of causing LAST. Furthermore, continuous infusion lidocaine postoperatively in the ward would require the patient to be connected to an infusion pump, which may be inconvenient and may thereby hinder the patient’s mobilisation.

As such, a relatively low dose of lidocaine was opted, which may not be potent enough to produce clinically significant improvement in pain and other physical parameters.

Current studies and meta-analyses have suggested that IV lidocaine infusion provides significant analgesic effects and improves bowel function primarily in patients undertaken major abdominal surgeries [13-15]. However, such efficacy is not routinely demonstrated in patients having orthopaedic surgeries [16-17]^, including this study.

The reason for the discrepancy observed is not clear. Biochemically, the blood level of inflammatory mediators has been shown to be smaller and briefer after unilateral total hip replacement than after major abdominal surgeries [18]. Thus, for orthopaedic procedures, such as joint arthroplasty, which might possibly cause a lesser degree of inflammation , IV lidocaine might be less effective given anti-inflammation as one of its main mechanisms.

Clinically, patients undertaken orthopaedic surgeries are commonly encouraged to resume oral feeding and to mobilise through a more rigorous and structured rehabilitation program than patients undertaken major abdominal surgeries. These principles of ERAS, including multimodal opioid-sparing analgesia such as the regime used in this study, promote bowel movement. The effects of IV lidocaine on improving the bowel functions might therefore be less apparent in this patient population.

Moreover, the present study was powered solely for the primary endpoints. Significant difference on return of bowel function could possibly be unveiled after inclusion of a larger patient population. In fact, although not statistically significant, a lower incidence of constipation was observed in the Lidocaine group on POD 1-3 with less proportion of patients in the Lidocaine group in need of laxatives. For POD 1 (p = 0.082, 16.13% vs. 35.48%); POD 2 (p = 0.562, 22.58% vs. 29.03%); POD 3 (p = 1, 10.00% vs. 18.75%).

One limitation of this study was the relative low dose of a single bolus of IV lidocaine used. It is understood that a single bolus is less ideal than infusion in damping the inflammatory storms after TKA, which typically surge on POD 3 [19]. However, as discussed above, without the benefits of previous trials demonstrating the safety profiles of IV lidocaine in TKA, such was constrained by the concomitant use of LIA and the intent of promoting early mobilisation.

Secondly, the lidocaine concentrations and the cytokines levels were not measured in the present study. These parameters are believed to be important as they might explain the apparently varied effects of IV lidocaine between TKA and other major abdominal surgeries.

Thirdly, we did not study the long-term outcomes of peri-operative IV lidocaine administration. In fact, some available data now suggest that a brief period of perioperative lidocaine administration, despite the lack of short-term benefits, may improve long-term outcomes after complex spine surgeries [20] and breast surgeries [21].

Whilst this study failed to demonstrate a statically significant reduction in NRS and morphine consumption in the Lidocaine group, it suggested an improvement in other parameters that may have led to a shorter hospital stay.

Further research should therefore aim at studying the biochemical pattern of inflammatory mediators generated after TKA and thereby attempt to devise an optimal dosing regimen of IV lidocaine for patients undergoing unilateral primary TKA. IV lidocaine remains an affordable and widely available addition to the analgesic regime that is integral to the enhanced recovery and rehabilitation of TKA.