Postoperative Analgesic Efficacy of Extended Opioid-free Anesthesia Regimen with Intravenous Lignocaine versus Morphine Following Major Head and Neck Surgeries

Abstract

Background and Aims:

Opioids are commonly used for postoperative analgesia, but concerns about their potential link to cancer progression and metastasis have led to interest in opioid-free regimens. Intravenous lignocaine, with its analgesic and potential anticancer properties, is emerging as an alternative. We aimed to compare the incidence of inadequate postoperative analgesia and the need for rescue medications between intravenous lignocaine and morphine following major head and neck surgeries.

Methods:

This retrospective observational study included 40 adult patients who had undergone major head and neck surgeries with reconstruction, divided into two groups. Group M received morphine 0.02 mg/kg/h infusion, and Group L received lignocaine 0.5 mg/kg/h infusion for postoperative analgesia. Data on hemodynamic responses, rescue analgesic use, and ventilation duration were extracted from electronic medical records and intensive care unit nurses’ charts. Inadequate analgesia was defined as a >20% increase in heart rate or mean arterial pressure (MAP) from baseline.

Results:

Group L showed a significantly lower incidence of inadequate analgesia (20%) compared to Group M (20% vs. 80%, P = 0.0002). Patients in Group L required significantly less rescue clonidine (P < 0.001) and had significantly lower total dexmedetomidine consumption and duration of infusion. Mean heart rate and MAP were significantly higher in Group M at various postoperative time points. Postoperative ventilation duration was comparable between the groups.

Conclusion:

Intravenous lignocaine significantly reduced inadequate analgesia and need for rescue medications with optimal hemodynamics in the immediate postoperative period following major head and neck surgeries. Further large-scale, prospective, randomized controlled trials are warranted.

INTRODUCTION

Currently, a possible linkage between opioid use and progression of cancer disease or metastasis has been postulated.[1] However, opioids are the most prescribed analgesics, both in the intraoperative and immediate postoperative periods, following major head and neck surgeries as the role of regional blocks to provide analgesia is limited in such surgeries. The use of lignocaine as a part of opioid-free anesthetic regimen is gaining popularity now as lidocaine has shown to inhibit proliferation, invasion, and migration and hence could possibly induce apoptosis in several cancers.[2,3] Due to its excellent analgesic property,[4] it could be a useful postoperative analgesic alternative to opioids.

The primary objective of our study was to compare the incidence of inadequate analgesia, as indicated by hemodynamic responses requiring rescue medications, between the groups which received intravenous lignocaine or morphine in the immediate postoperative period. The secondary objectives included a comparison of the total postoperative opioid consumption, time to cessation of mechanical ventilation, and the use of rescue analgesics between the groups that received lignocaine and the group that received morphine.

METHODS

The present study was a retrospective one. The data collection was performed after obtaining institutional ethical committee clearance (IEC-AIMS-2025-ANAE-158, dated 25-07-2025). The inclusion criteria were surgical patients who had undergone major head and neck surgeries with reconstruction under general anesthesia, aged ≥18 years, and had received either intravenous morphine infusion or intravenous lignocaine infusion intraoperatively. The patients ventilated overnight for approximately 12 h postoperatively with complete electronic medical records available for data extraction were only included. The patients with known allergies or contraindications to morphine or lignocaine, those who received other continuous intraoperative analgesic infusions such as ketamine, those who had preexisting chronic pain conditions requiring continuous opioid therapy, or those who had incomplete medical records lacking essential outcome data were excluded.

As there are no similar studies published in the past, we conducted a pilot study aimed to compare the incidence of inadequate postoperative analgesia, as indicated by hemodynamic responses necessitating the need for rescue medications, between the groups which received intravenous lignocaine or morphine in the immediate postoperative period. Two equal groups of 20 patients were formed. In the morphine group, 80% of patients required rescue analgesia, whereas it was only 30% of patients in the lignocaine group. Based on these data, with a 95% confidence interval and 90% power, the sample size was calculated to be 16 patients per group. Therefore, 20 patients per group totaling to 40 were included in the present study.

We utilized a retrospective cohort design to analyze existing data from patients who underwent major head and neck surgeries. Data were extracted from the electronic medical records of the patients who underwent these procedures between 2022 and 2024. The patients were grouped into two based on the primary intraoperative analgesic they had received. Group M comprised patients who had received a continuous intravenous infusion of morphine at a rate of 0.03–0.05 mg/h during the intraoperative period. At the end of the surgery, the morphine infusion rate was reduced to 0.02 mg/kg/h and continued in the immediate postoperative period. Patients in Group L had received a continuous intravenous infusion of lignocaine at a rate of 1 mg/kg/h during the intraoperative period. At the end of the surgery, the lignocaine infusion rate was reduced to 0.5 mg/kg/h and continued postoperatively.

Following the surgical procedure, patients in both the groups were ventilated overnight for approximately 12 h. During this period, inadequate analgesia was primarily assessed based on hemodynamic responses. An increase in heart rate of >20% from the baseline value or an increase in mean arterial pressure (MAP) of >20% from the baseline value was taken as a surrogate of inadequate analgesia. The first line of management was clonidine 0.5 mcg/kg administered as an intravenous bolus. If the hemodynamic parameters did not improve, the same dose of clonidine was repeated after 10 min. If inadequate analgesia persisted despite the repeated clonidine dose, a bolus dose of dexmedetomidine 0.5 mcg/kg followed by continuous intravenous infusion of dexmedetomidine was started at a rate of 0.3–0.7 mcg/kg/h and titrated to maintain hemodynamic parameters within an acceptable range.

After approximately 12 h of ventilation, sedation (morphine infusion) was stopped in the morphine group, and in the lignocaine group, lignocaine infusion was stopped. If any patient in either group was receiving dexmedetomidine infusion, it was also discontinued. Weaning from mechanical ventilation began with a T-piece trial for patients in both the groups when they were awake and able to generate sufficient tidal volume and respiratory rate. Subsequent postoperative analgesia in both the groups was provided according to a standardized institutional protocol, with intravenous paracetamol 15 mg/kg 6^th hourly and tramadol 1 mg/kg 8^th hourly.

Data were extracted from the electronic medical records, anesthesia, and intensive care unit (ICU) charts. The data collected were patient demographics such as age, gender, body mass index (BMI), and American Society of Anesthesiologists physical status (ASA PS). Surgical details, including the type of surgery, duration of surgery and information regarding intraoperative medications, the start and end times of the morphine or lignocaine infusion, and the total doses administered were also noted.

The values of heart rate and MAPs were collected at immediate postoperative period and then 15, 30, 45, 60, 90, 120, 150, and 180 min postoperatively. Further recordings were made hourly till 6 h and then 2 hourly till 12 h or at the end of mechanical ventilation. Episodes of increased heart rate >20% from baseline or MAP >20% from baseline were noted. The administration of rescue analgesics in the immediate postoperative period, such as requirement of clonidine and/or dexmedetomidine, was noted. The total consumption of clonidine and dexmedetomidine and the duration of dexmedetomidine infusion were also documented. The details regarding postoperative ventilation, including the total duration of mechanical ventilation in hours, were also documented.

For statistical analysis, the continuous variables were compared using an independent samples t-test if the data were normally distributed. If the data were not normally distributed, the Mann–Whitney U test was utilized. Categorical variables, including the incidence of inadequate analgesia and the binary use of rescue analgesics, were compared between the groups using a Chi-square test or Fisher’s exact test. Continuous variables with skewed distributions such as consumption of clonidine, dose, and duration of dexmedetomidine infusion were presented as median with interquartile range (IQR). The use of rescue analgesics was compared utilizing Mann–Whitney U test. Descriptive statistics and comparative analysis were calculated using MedCalc Software Ltd., Ostend, Belgium.

RESULTS

Data of 40 patients were analyzed. The patient demographics were comparable between Group M and Group L. The mean age was 58.62 ± 8.27 years in Group M and 62.03 ± 5.81 years in Group L, with no significant difference between the groups. Similarly, the distribution of gender, BMI, ASA PS, and duration of surgery also showed no significant differences between the two groups [Table 1].

Table 1.

Comparison of demographic details, American Society of Anesthesiologists physical status, and duration of surgery

Variables	Group M	Group L	P
Age (years), mean±SD	58.62±8.27	62.03±5.81	0.140
Male, n (%)	12 (60)	11 (55)	0.749
Female, n (%)	8 (40)	9 (45)
BMI (mean±SD)	28.72±2.32	26.96±3.88	0.090
ASA PS II, n (%)	7 (35)	5 (25)	0.490
ASA PS III, n (%)	13 (65)	15 (75)
Duration of surgery (h), mean±SD	8.65±2.41	8.91±4.29	0.815

ASA PS=American Society of Anesthesiologists physical status, BMI=Body mass index, SD=Standard deviation

Group M demonstrated a significantly higher incidence of inadequate analgesia compared to Group L (80% vs. 20%, P = 0.0002). The median rescue clonidine dose was 60 mcg (IQR: 45) in Group M, while Group L required 0 mcg (IQR: 15), which was statistically significant (P < 0.001). Only 4 patients in Group M and 2 patients in Group L required dexmedetomidine infusion. Although there was no significant difference in the number of patients requiring dexmedetomidine infusion (20% in Group M vs. 10% in Group L), the duration of dexmedetomidine infusion (P = 0.008) and total dexmedetomidine consumption (P = 0.008) were significantly higher in Group M (median duration: 0 h, IQR: IQR: 10.25; median consumption: 0 mcg, IQR: 342) compared to Group L (median duration: 0 h, IQR: 0; median consumption: 0 mcg, IQR: 0). Postoperative ventilation duration did not differ significantly between the groups [P = 0.42, Table 2].

Table 2.

Comparison of incidence of inadequate analgesia, dose of rescue clonidine, patients who required dexmedetomidine infusion with dose and duration of dexmedetomidine infusion, and postoperative ventilation

Outcome	Group M	Group L	P
Inadequate analgesia, n (%)	16 (80)	4 (20)	0.0002
Rescue clonidine dose, median (IQR)	60 (45)	0 (15)	<0.001
Patients who required dexmedetomidine infusion, n (%)	4 (20)	2 (10)	0.382
Duration of dexmedetomidine infusion (h), median (IQR)	0 (10.25)	0	0.008
Total dexmedetomidine consumption (µg), median (IQR)	0 (342)	0	0.008
Postoperative ventilation duration (h), mean±SD	11.73±1.03	12.01±1.23	0.42

IQR=Interquartile range, SD=Standard deviation

The mean heart rate was significantly higher in Group M in the postoperative period up to 180 min and at 6 h after surgery compared with Group L (P < 0.05). There was no significant difference in mean heart rate in both the groups at other time points [Table 3]. MAP was significantly higher in Group M till 120 min in the postoperative period. At other time points, both Group M and Group L had comparable MAP [Table 4].

Table 3.

Comparison of mean heart rate

Time	Group M, mean±SD	Group L, mean±SD	P
Immediate postoperative	94.55±17.62	80.78±11.39	0.006
15 min postoperative	98.84±11.93	80.18±7.24	<0.001
30 min postoperative	95.82±9.61	76.56±4.89	<0.001
45 min postoperative	90.37±8.42	70.58±6.52	<0.001
60 min postoperative	89.97±5.68	68.35±3.76	<0.001
90 min postoperative	86.43±4.14	75.97±7.19	<0.001
120 min postoperative	83.41±6.83	74.83±6.88	<0.001
150 min postoperative	82.59±4.50	78.15±7.65	0.0312
180 min postoperative	75.67±5.34	68.73±3.39	<0.001
4 h postoperative	70.32±10.02	65.55±4.88	0.0632
5 h postoperative	76.58±5.69	72.46±8.63	0.0827
6 h postoperative	72.27±1.33	68.36±4.39	<0.001
8 h postoperative	71.55±7.68	68.64±3.34	0.1285
10 h postoperative	72.96±3.74	70.32±7.18	0.1530
12 h postoperative/end of mechanical ventilation	78.94±10.13	76.51±0.68	0.2912

SD=Standard deviation

Table 4.

Comparison of mean arterial pressure

Time	Group M, mean±SD	Group L, mean±SD	P
Immediate postoperative	104.71±7.54	90.23±8.68	<0.0001
15 min postoperative	113.62±10.93	94.15±7.85	<0.0001
30 min postoperative	109.56±7.93	89.47±10.52	<0.0001
45 min postoperative	102.33±7.84	86.37±6.46	<0.0001
60 min postoperative	98.45±11.14	88.46±8.75	0.0031
90 min postoperative	84.6±6.01	90.4±8.42	0.0166
120 min postoperative	85.49±5.26	80.51±1.22	0.0002
150 min postoperative	88.64±7.75	85.14±8.77	0.1890
180 min postoperative	89.65±10.48	91.98±9.47	0.4652
4 h postoperative	90.21±8.25	88.36±6.62	0.4390
5 h postoperative	89.83±5.91	86.34±5.94	0.0703
6 h postoperative	88.46±13.27	82.56±11.7	0.1441
8 h postoperative	83.41±6.83	86.4±13.21	0.3742
10 h postoperative	82.45±11.16	80.2±10.23	0.5103
12 h postoperative/end of mechanical ventilation	86.49±13.24	81.8±12.98	0.2650

SD=Standard deviation

DISCUSSION

Major head and neck cancer surgeries present unique postoperative pain management challenges due to complex nociceptive and neuropathic components, extensive tissue disruption, and frequent opioid tolerance in cancer populations.[5] Our study evaluated intravenous lignocaine’s efficacy compared to morphine, focusing mainly on the immediate postoperative analgesia.

Lignocaine exerts multimodal effects through sodium channel blockade, anti-inflammatory cytokine modulation (e.g., interleukin IL-6 and tumor necrosis factor-alpha [TNF-α] reduction), and inhibition of neutrophil priming. These mechanisms may counteract surgical stress-induced hyperalgesia, particularly relevant in cancer resections where TNF-α release exacerbates peripheral sensitization.[,7,8] Morphine, while effective for nociceptive pain, lacks neuropathic coverage and may promote immunosuppression through µ-opioid receptor-mediated pathways, a concern given cancer surgery’s curative intent.[9]

A randomized trial comparing perioperative lignocaine (1.5 mg/kg bolus with 2 mg/kg/h intraoperative infusion) to placebo found equivalent 48-h morphine consumption (44 mg vs. 38 mg, P = 0.92).[10] However, pain scores at rest and movement showed nonsignificant reductions in the lignocaine group during the first 24 h.[10] This aligns with multimodal analgesia protocols demonstrating 28%–35% opioid reduction when combining lignocaine with nonsteroidal anti-inflammatory drugs and gabapentin.[11] The discrepancy between biochemical anti-inflammatory effects and clinical opioid-sparing outcomes[10] suggests lignocaine’s primary benefit may lie in attenuating central sensitization rather than direct analgesic potency.[,13,14]

Head and neck cancer patients exhibit altered pain processing due to preexisting tumor-related inflammation and frequent preoperative opioid exposure.[5] Lignocaine’s N-methyl-D-aspartate (NMDA) receptor antagonism could theoretically mitigate opioid-induced hyperalgesia, though this remains unproven in opioid-naive cancer populations.[9,10] No significant difference emerged in neuropathic pain scores at 3–6 months,[10] contrasting with breast cancer trials showing significant reductions in chronic postsurgical pain with perioperative lidocaine infusions.[15,16] This may reflect divergent neural injury patterns; head and neck procedures often sacrifice cervical plexus branches, creating irreversible deafferentation pain less responsive to perioperative interventions.

The clinical implications of the use of lignocaine in head and neck cancer surgeries are dosing optimization, tumor microenvironment effects, and immune modulation. Current protocols of 2 mg/kg/h lignocaine intraoperatively yield plasma concentrations (1.5–2 µg/mL) below the antiarrhythmic range but may be subtherapeutic for neuropathic components.[,18,19] Animal models suggest 5 µg/mL required for NMDA inhibition, achievable through 3 mg/kg/h infusions.[,20,21] Experimental data indicate that lignocaine suppresses matrix metalloproteinases and circulating tumor cell adhesion which are potential antimetastatic effects needing clinical validation.[9] Lignocaine had shown a lower postoperative neutrophil–lymphocyte ratio, a prognostic marker in head and neck squamous cell carcinoma, mostly due to immunomodulation.

A contrasting observation was made in a trial which showed intravenous lidocaine in otolaryngological cancer surgery did not result in any additional analgesic or morphine-sparing effect 48 h after surgery.[10] This contrasts with positive abdominal surgery trials, possibly due to anatomical complexity, dual somatic (cutaneous) and visceral (pharyngeal) innervation. Other factors could be concurrent radiotherapy as prior radiation could induce fibrotic pain mechanisms. Duration of infusion could also influence these results as discontinuing lignocaine as early as 4 h postoperatively may miss the peak inflammatory mediator release at 12–24 h.[22]

While intravenous lignocaine does not surpass morphine for acute opioid-sparing, its immunologic profile and neuropathic coverage rationale justify its inclusion in multimodal regimens for head and neck cancer surgery. The substantial clinical differences observed in our study underscore lignocaine’s multimodal analgesic benefits, including its anti-inflammatory and neuropathic pain-modulating effects, which are particularly advantageous in head and neck cancer surgery. Despite the limitations inherent to a retrospective design and the small sample size, our findings strongly support the integration of intravenous lignocaine as a valuable component in opioid-sparing or opioid-free anesthetic regimens for this patient population.

CONCLUSION

This retrospective observational study demonstrated that intravenous lignocaine infusion significantly reduced the incidence of inadequate analgesia and the need for rescue medications in the immediate postoperative period following major head and neck surgeries, compared to morphine. Specifically, patients receiving lignocaine experienced a four-fold lower rate of inadequate analgesia and required significantly less rescue clonidine and dexmedetomidine. Further large-scale, prospective, randomized controlled trials are essential to confirm these benefits, investigate long-term outcomes, and optimize lignocaine dosing strategies.

Conflicts of interest

There are no conflicts of interest.

Funding Statement

Nil.