Optimising Pain Management in Paediatric Tonsillectomy: Evaluation of Intravenous Lidocaine at a 50% Efficacy Dose for Postoperative Throat Pain Prevention

doi:10.21203/rs.3.rs-3204763/v1

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Optimising Pain Management in Paediatric Tonsillectomy: Evaluation of Intravenous Lidocaine at a 50% Efficacy Dose for Postoperative Throat Pain Prevention

https://doi.org/10.21203/rs.3.rs-3204763/v1

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Background:
Intravenous lidocaine is effective in preventing post-operative throat pain. However, concerns about lidocaine toxicity and limited administration methods persist. Consequently, the optimal 50% effective dose (ED₅₀) of lidocaine for preventing post-operative throat pain in children undergoing tonsillectomy remains unclear.

Methods:
We enrolled 27 children aged 3 to 15 years who underwent tonsillectomy. A predetermined continuous lidocaine infusion (1.5 mg/kg) was administered throughout the surgery. Throat pain was assessed at 1 h post-operation using the Children’s and Infants’ Postoperative Pain Scale (CHIPPS) and visual analogue scale (VAS) scores. The lidocaine administration rate for each subsequent child was determined based on the scores. The initial child received lidocaine at a rate of 0.5 mg/kg/h, and subsequent children received higher rates if the CHIPPS or VAS score was ≥ 4 at 1 h post-operation. Those with a CHIPPS or VAS score < 4 received the same or lower rates. All patients received the same induction protocol (sufentanil, propofol, and rocuronium), and anaesthesia was maintained using sevoflurane. The primary outcome was the CHIPPS or VAS score for throat pain at 1 h post-operation. The secondary outcomes were post-operative nausea, vomiting, and time to extubation. Intra-operative respiratory and cardiac events were monitored for safety.

Results:
The ED₅₀ of intravenous lidocaine for throat pain was determined to be 0.477 (0.378–0.617) mg/kg/h. The effective dose for preventing post-operative throat pain in 95% of patients administered lidocaine was 0.624 (0.545–2.458) mg/kg/h.

Conclusions:
Intravenous lidocaine (ED₅₀) effectively treats post-operative throat pain in children.

TRIAL REGISTRATION:

This study was approved by the Institutional Review Board of Yichang Central People’s Hospital (HEC-KYJJ-2020-038-04) on 16 Feburary 2023. The trial was registered on 21 Mach 2023(21/03/2023) at www.chictr.org.cn (ChiCTR2300069567).

lidocaine

post-operative

throat pain

ambulatory tonsillectomy

50% effective dose (ED50)

children

Tonsillectomy is a common ambulatory surgical procedure in children that involves general anaesthesia.^1,2 The goal of ambulatory tonsillectomy protocols is to minimise post-operative complications and speed up recovery. The most common post-operative complication following tonsillectomy is throat pain, which may lead to dehydration, delayed return to normal activities, and reduced patient and parental satisfaction. Therefore, adequate and effective management of post-operative pain is recommended based on the guidelines.^3–5 Various methods have been used to prevent post-operative throat pain, such as optimising airway designs, minimising intracuff pressures, and administering ketamine or lidocaine.⁵

Lidocaine is commonly used as an adjunct to general anaesthetic through systemic intravenous administration. A standard preload dose of 1.5 mg/kg is widely accepted, and the lidocaine infusion rate varies greatly from 0.5 to 2 mg/kg/h. A previous study demonstrated that intravenous lidocaine could reduce post-operative complications, including pain, nausea, and vomiting (PONV), in children.⁶ However, the low therapeutic index of intravenous lidocaine increases the risk of central nervous system toxicity, which can occur at slightly higher plasma levels than therapeutic levels, thereby limiting its application.⁷ Further research is needed to ensure the safe and effective use of lidocaine, with the median effective dose (ED₅₀) of intravenous lidocaine being uncertain in children.

Therefore, this study aimed to determine the ED₅₀ of lidocaine in children who underwent tonsillectomy. The selection of throat pain as the primary outcome was guided by the need for clinically meaningful outcomes with potential benefits. We believe that this study will help improve the understanding and promote the use of lidocaine in paediatric anaesthesia.

Study design

This single-centre, investigator-initiated trial was conducted from 1 April 2023 to 1 May 2023 at Yichang Central People’s Hospital. The study was approved by the Institutional Review Board of Yichang Central People’s Hospital (HEC-KYJJ-2020-038-04) and was registered at www.chictr.org.cn (ChiCTR2300069567) on 21 March 2023. Written informed consent was obtained from the parents of each child.

Patients

A total of 27 patients aged 3 to 15 years (American Society of Anaesthesiologists [ASA] I–II) who underwent scheduled selective tonsillectomy with an estimated operation time ≤ 120 min were included in this study. The exclusion criteria were as follows: body mass index ≤ 14 kg/m² or ≥ 32.9 kg/m²; body weight ≤ 10 kg; allergy against opioids; administration of analgesic, sedative, emetic, or antipruritic agents within 24 h before surgery; body temperature > 38 ℃ or acute upper respiratory tract infection within 24 h before surgery; history of bronchial asthma; moderate to severe sleep apnoea syndrome; participation in other clinical trials within 1 month; or other conditions deemed unsuitable for inclusion.

Perioperative anaesthetic care

Before the operation, all children were instructed to fast for 8 h and avoid clear fluids for 2 h. Parents were allowed to accompany their children into the operating room to alleviate separation anxiety. Vital signs, including non-invasive blood pressure (BP), heart rate (HR), electrocardiography findings, and pulse oxygen saturation, were continuously monitored using a multifunction monitor (GE Healthcare, Helsinki, Finland). The width of the BP cuff was approximately two-thirds of the upper arm length for each child. After a 5-min stabilisation period, baseline systolic and diastolic BP, mean arterial pressure, and HR were measured by taking the average of three readings obtained 2 min apart. An intravenous catheter (22-gauge) was inserted into the veins of the dorsum of the hand.

Following routine preoxygenation, lidocaine was intravenously injected over 5 min at a dose of 1.5 mg/kg with pump activation under the supervision of an anaesthesiologist. The study treatments were infused after the injection was completed. A nurse anaesthetist, who was not involved in data recording but prepared the treatments, activated the pump to infuse the study drugs. General anaesthesia was then induced using the following protocol: 0.25 µg/kg sufentanil, 2.0 mg/kg propofol, and 0.6 mg/kg rocuronium. If the eyelash reflex was absent, the child was ventilated using a facemask with 100% oxygen.

A cuffed endotracheal tube was used, and its size was determined using a widely accepted formula (3.5 + age in years/4). Patients who experienced difficulty during facemask ventilation were excluded from the study. Prophylactic treatments for PONV included dexamethasone (0.15 mg/kg) and ondansetron (0.1 mg/kg). Anaesthesia was maintained with 2–3% sevoflurane and 50% medical air in oxygen.

The surgery was performed by an experienced surgeon (Xiao-bo Zhang). At the end of the operation, sevoflurane and intravenous lidocaine were discontinued, and neostigmine (0.04 mg/kg) and atropine (0.02 mg/kg) were administered to antagonise any residual neuromuscular blockade, which was confirmed on a neuromuscular monitor showing a train-of-four value > 0.7. Following the completion of the surgery, oral suction was performed immediately after removing the endotracheal tube. Extubation was performed after confirming adequate tidal volume, regular spontaneous respiratory patterns, and purposeful behaviour (eyes open upon request). After extubation, the children were monitored for at least 5 min to ensure regular spontaneous respiration before being transferred to the post anaesthesia care unit (PACU). Electrocardiography, peripheral pulse oximetry, and non-invasive BP measurements were performed. Throat pain assessment was conducted by an anaesthetist (Xiang Long), who was blinded to the study, at 1 h post-operation using the Children and Infants Postoperative Pain Scale (CHIPPS) or visual analogue scale (VAS).⁸

The initial preload of lidocaine was 1.5 mg/kg, followed by an infusion rate of 0.5 mg/kg/h for the first patient. The infusion rate was then adjusted using Dixon’s up-and-down method based on the score of throat pain at 1 h post operation. If the score was ≥ 4, the infusion rate was increased by 0.05 mg/kg/h in the next patient. If the score was < 4, the infusion rate was decreased by 0.05 mg/kg/h in the next patient. The trial was terminated after six reflexes.⁹

Patients were discharged from the PACU to the ward when their Steward recovery score was > 4, and they stayed there overnight. Other perioperative care was provided according to local clinical practices.

Primary outcomes

The primary outcome was throat pain 1 h post operation. The CHIPPS or VAS was used to rate the throat pain score. The VAS was used for children older than 5 years. Intravenous paracetamol (15 mg/kg) was administered as a rescue medication by an attending PACU nurse during the post-operative phase.

Secondary outcomes

The secondary outcome measures were time to extubation and the incidence of PONV within 24 h postoperatively. Safety elements included intra-operative respiratory complications (laryngospasm, oxygen desaturation, and upper airway obstruction), cardiac events during surgery (arrhythmia, hypotension defined as mean arterial pressure ≤ 20% from baseline for 3 min, and hypertension defined as mean arterial pressure ≥ 20% from baseline for 3 min), and rescue medication.

Statistical analysis

Statistical analysis was performed using GraphPad Prism 8.0.2 (GraphPad Software Inc. San Diego, California, USA) and Statistical Package for the Social Sciences version 26.0 software (IBM, Armonk, NY, USA). The minimum required sample size for analysis was eight crossover pairs. One-way analysis of variance (ANOVA) was utilised to analyse the extubation time. Patient characteristics, such as age, height, weight, time of operation, and extubation, are presented as mean ± standard deviation and were analysed using ANOVA. Probit regression analysis was used to determine the ED₅₀ and 95% confidence intervals (CI) of lidocaine. The incidences of PONV were expressed as ratios and were analysed using Fisher’s exact test. A P-value < 0.05 was considered statistically significant for all analyses.

Between 1 April March 2023 and 1 May 2023, 27 paediatric patients (20 male and 7 female) were included in the study, all of whom underwent tonsillectomy with adenoidectomy. The age of the patients ranged from 4 years 11 months to 12 years 6 months. The relationship between the rate of lidocaine infusion and the throat pain score at 1 h post operation is illustrated in Fig. 1. Among the 27 patients, 14 had a throat pain score ≥ 4 at 1 h post-operation, whereas the remaining 13 had a score < 4.

The ED₅₀ of intravenous lidocaine for attenuating throat pain at 1 h post-operation was found to be 0.447 mg/kg/h (95% CI: 0.378–0.617), and the ED₉₅ was 0.624 mg/kg/h (95% CI: 0.545–2.458). The incidence of PONV was found to be 0. No severe complications, such as post-operative hypoxemia, laryngospasm, or arrhythmia, were observed during the trial.

Our study demonstrated the effectiveness of intravenous lidocaine in paediatric post-tonsillectomy pain management. The ED₅₀ of lidocaine for preventing post-operative throat pain in children at 1 h post-tonsillectomy was determined to be 0.477 mg/kg/h (95% CI: 0.378–0.617), with an ED₉₅ of 0.624 mg/kg/h (95% CI: 0.545–2.458). In addition, no severe complications such as post-operative hypoxemia, laryngospasm, or arrhythmia were noted.

Ambulatory tonsillectomy protocols play a crucial role in ensuring the prompt and efficient recovery and discharge of patients from the hospital, particularly in the post-operative period. Post-tonsillectomy throat pain is primarily caused by inflammation, with mechanical stimulation intensifying the background discomfort, which is usually intense and associated with post-operative pain.^8,10 The use of lidocaine infusion for post-tonsillectomy pain management is conceptually appealing because of its analgesic, anti-hyperalgesia, and anti-inflammatory properties.¹¹ Previous studies have shown that lidocaine infusion has a positive impact on pain scores in the early post-operative phase (1–4 h post operation) compared with placebo.^12,13 Similarly, our study found that intravenous lidocaine can reduce post-operative pain scores at 1 h post-operation.

Balancing the need for post-operative analgesia with the desire for a swift transition to simpler pain management methods poses a challenge for anaesthesiologists during tonsillectomy. Our study demonstrated that short-term infusions of lidocaine provide prolonged pain relief in both clinical and laboratory models.^14,15 Lidocaine infusion may be a better choice for pain management during the perioperative phase, as the use of post-operative codeine or other opioids is restricted due to concerns about respiratory depression and delayed hospital discharge.¹⁶ The combination of non-steroid anti-inflammatory drugs with paracetamol or tramadol in different conditions is recommended for pain management after hospital discharge.⁸ Importantly, our study did not observe any severe adverse events, such as post-operative hypoxemia, laryngospasm, or arrhythmia, suggesting that the goal of shifting to a simple analgesic method with improved post-tonsillectomy analgesia may be achieved through lidocaine infusion.

The narrow therapeutic index of intravenous lidocaine has raised concerns about its potential toxicity. In our study, regarding lidocaine toxicity, we administered general anaesthesia without additional local anaesthetic, and the findings revealed that the ED₉₅ of lidocaine infusion in paediatric tonsillectomy at 1 h post-operation was 0.624 mg/kg/h (95% CI: 0.545–2.458), which is lower than the infusion rate used in most trials. This observation highlights the potential risk of lidocaine accumulation and associated toxicity. At low infusion doses, lidocaine poses no notable safety concerns. However, we observed that lower infusion rates may increase post-operative pain scores. These results highlight the need for further studies to determine optimal infusion rates. Additionally, our findings demonstrated that intravenous lidocaine does not result in significant adverse events, even at lower rates. The incidence of PONV was 0 in this study, which is interesting. However, it should be noted that the small sample size may have influenced this finding.

This study has some limitations. First, it was conducted at a single centre, reducing its power and reliability. Second, we did not measure the plasma concentration of lidocaine. Finally, we did not study the relationship between infusion time and potential safety hazards.

The results of our study reveal that intravenous lidocaine effectively prevents post-operative throat pain in children undergoing tonsillectomy without causing any serious adverse events. In the future, further studies should focus on determining the optimal infusion rate of lidocaine, specifically balancing its efficacy and potential toxicity.

i) Ethics approval and consent to participate

The study has been conducted in accordance with the principles set forth in the Helsinki Declaration, and all patients provided written informed consent for participation in the research study.

Ethical approval for this study (HEC-KYJJ-2020-038-04). was provided by the Institutional Review Board of Yichang Central People’s Hospital, Wujiagang District, Yichang City, Hubei Province (chairman: Yan Kejun) on 16/02/2023.

ii) Consent for publication

Yes

iii) Availability of Data and Material

The data associated with the paper are available from the corresponding author (YG) on reasonable request.

iv) Competing interests

None

v) Funding

Support was provided solely from institutional sources.

vi) Authors' contributions

Data Curation, YH, and YC; Software and Formal Analysis, YH and GQ; Resources and Investigation, QZ and GZ; Project Administration, XL and JJ; Methodology, Supervision, and Validation, YG. All authors read and approved the final version of the manuscript.

vii) Acknowledgment

None

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Hawley K. Tonsillectomy and adenoidectomy in children. JAMA Otolaryngol Head Neck Surg 2019; 145: 300.
Xu YJ, Wang SL, Ren Y, Zhu Y, Tan ZM. A smaller endotracheal tube combined with intravenous lidocaine decreases post‐operative sore throat – a randomized controlled trial: Smaller tube with lidocaine reduces sore throat. Acta Anaesthesiologica Scand 2012; 56: 1314-20.
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No competing interests reported.

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Optimising Pain Management in Paediatric Tonsillectomy: Evaluation of Intravenous Lidocaine at a 50% Efficacy Dose for Postoperative Throat Pain Prevention

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Version 1

Abstract

Figures

Introduction

Materials and Methods

Study design

Patients

Perioperative anaesthetic care

Primary outcomes

Secondary outcomes

Statistical analysis

Results

Discussion

Conclusions

Declarations

References

Additional Declarations

Status:

Version 1