Discussion
Our study showed that intraoperative infusion of low dose lidocaine decreased postoperative opioid requirement and pain intensity in comparison with normal saline in patients undergoing laparoscopic TEP inguinal hernia surgery. Patients receiving lidocaine had fewer occurrences of PONV, a better quality of recovery and were more satisfied with postoperative pain relief than those receiving saline. Patients complained of pain later in the lidocaine group than the saline group. No significant difference was observed for postoperative sedation and the incidence of chronic pain in 3 months.
It is well-established that lidocaine acts on voltage-gated sodium channels when administered locally for peripheral nerve block. However, at lower concentration systemic lidocaine is insufficient to produce direct analgesia solely by blocking the neuronal sodium channels.[17] Although it is not fully understood how intravenous lidocaine produces analgesia, several potential mechanisms have been elucidated. Intravenous lidocaine increases acetylcholine concentration at the spinal level through an activation of both muscarinic and nicotinic receptors, and thereby prolongs the pain threshold.[18] Also, by activating central glycine (an inhibitory neurotransmitter) receptor, systemic lidocaine inhibits glutamate-induced excitatory response on the wide dynamic response in the spinal neurons.[19] The anti-hyperalgesic effect of IV lidocaine is due to blockade of NMDA receptor signaling and it is mediated indirectly by inhibition of the protein kinase C pathway.[20] In addition to this, systemic lidocaine has anti-inflammatory properties as a decline in pro-inflammatory cytokines is observed in patients receiving lidocaine infusion.[21–23] Because perioperative pain is linked to an inflammatory process, modulation of this phenomenon with the administration of systemic lidocaine could significantly reduce pain. Another relevant question is to explain how the intraoperative administration of IV lidocaine does reduces opioid and pain scores beyond its infusion period. This could be due to its action on various receptors and signal cascades that produces an anti-nociceptive, anti-hyperalgesia and anti-inflammatory effects.[8]
Because of its influence in several pain pathways, systemic lidocaine is widely investigated adjuvant in the regimen of multimodal analgesia to reduce postoperative opioid consumption and pain. Although the majority of studies have demonstrated the analgesic effect of lidocaine, several other trials failed to confirm it. A recently updated Cochrane review in 2018 has provided a much-needed insight on the analgesic property of systemic lidocaine.[9] Random-effects meta-analysis from the same review on overall total postoperative opioid consumption favored lidocaine compared to the placebo (standardized mean difference (SMD) − 4.52 (mg, morphine equivalents (MEQ), 95%CI − 6.25 to− 2.79, p < 0.001; I2 = 73%; 40 studies, 2201 participants). The results of our study also indicated a similar reduction in total postoperative opioid consumption in the first 24 h after surgery in the lidocaine group compared to the saline group (median difference of − 4 mg morphine equivalents), despite using multimodal analgesia in both the groups.
Further, the aforementioned meta-analysis[9] demonstrated reduced pain scores at rest ("early time points"- in the PACU or 1 to 4 h postoperatively) in the lidocaine group compared to the control group (SMD − 0.50, 95% CI − 0.72 to− 0.28; Test for overall effect: Z = 4.41 (P < 0.0001). This was equivalent to an average pain reduction between 0.37 cm and 2.48 cm on a VAS 0 to 10 cm scale in the lidocaine group. Likewise, at intermediate time points (24 h postoperatively) the standardized mean pain score at rest in the lidocaine group was 0.14 lower (95% CI − 0.25 to − 0.04; Test for overall effect: Z = 2.63 (P = 0.0086). This was equivalent to an average pain reduction in the lidocaine group between 0.48 cm and 0.10 cm on a VAS 0 to 10 cm scale. These results showed that lidocaine exerted a clinical difference of at least 1 cm on a 0–10 VAS scores for pain at rest during early time points (1 to 4 h); however, this difference was not observed at intermediate (24 h) time points. We too observed statistically significant difference in pain scores up to 24 h postoperatively, while the clinical difference of approximately 1 cm in NRS scores at rest was observed only up to 1 h.
Due to substantial heterogeneity between studies, the authors of the same meta-analysis performed a sub-group analysis based on type of surgery, duration and dose of lidocaine infusions.[9] In the older version (Cochrane review, 2015) there was a clear beneficial effect in terms of pain reduction in laparoscopic abdominal surgery compared to open abdominal surgery.[6] However, in the current updated version, no significant difference was observed, although the trend was towards a beneficial effect for abdominal laparoscopic surgery.[9]
The optimal dose and time to terminate lidocaine infusion are still an unsolved issue. We had limited the duration of lidocaine infusion until the patients trachea was extubated due to a lack of dedicated infusion pumps and monitoring at the surgical unit. One might hypothesize that longer infusions would lead to more lasting analgesia but studies are yet to confirm this. The current meta-analysis (2018) had categorized the studies according to the usage of low (< 2 mg.kg− 1. h− 1) and high (≥ 2 mg.kg− 1 h− 1) lidocaine doses in combination with either short (until the end of surgery or until PACU) or long (≥ 24 h postoperatively) duration of infusion.[9] However, they did not find any difference in outcomes when the dose or duration of the infusion was compared. A well designed randomized comparative study with a large sample size is needed to explore whether the continuation of systemic lidocaine infusion beyond the surgical period is effective.
In our study, fewer patients receiving lidocaine complained PONV compared to those receiving saline infusions. Similar to our finding, the Cochrane meta-analysis (2018) reported a significantly lower frequency of nausea in the lidocaine group than in the control group, but the vomiting rates did not differ.[9] Although, there is an association between lidocaine therapy and reduction in PONV, it may not reflect a causal relationship. The most likely explanation for this association is related to lidocaine's opioid-sparing effects.
Recently, there is a growing interest in patient-reported outcomes such as postoperative QoR and patient satisfaction. We observed better recovery profiles at 24 h of surgery in the lidocaine group as evident from the QoR scores. Similar to our study, De Oliveira and his colleagues reported greater QoR-40 scores at 24 h with perioperative lidocaine infusion for laparoscopic abdominal surgery.[24,25] Likewise, in our study patient satisfaction was better in lidocaine than saline group and no patient expressed dissatisfaction over the intervention. The current meta-analysis also supports this finding by revealing higher satisfaction scores in patients receiving lidocaine compared to placebo group (SMD 0.76, 95% CI 0.46 to 1.06; I2 = 0%; 6 studies, 306 participants).[9] Further, perioperative lidocaine infusion reduces the length of hospital stay as compared to the placebo. We considered this outcome as a limitation in our study because all our participants were required to stay in the hospital for 24 h after surgery. In terms of patient-reported outcomes, it would be interesting to explore the influence of perioperative lidocaine on the enhancement of recovery profiles, especially after major abdominal surgeries in future trials. A more recent meta-analysis focused on CPSP (total 6 trials included: 4 mastectomies, 1 thyroidectomy, 1 nephrectomy) found that systemic lidocaine administration reduces the development of CPSP.[26] As our study was not powered enough to detect the protective effect of lidocaine on CPSP after laparoscopic TEP, we would not like to draw any conclusion. This could be explored in a larger, multi-centric trial with CPSP as a primary outcome.
BMC Anesthesiol. 2020;20(137) © 2020 BioMed Central, Ltd.
