Efficacy of Intravenous Lidocaine Infusions for Pain Relief in Children Undergoing Laparoscopic Appendectomy

A Randomized Controlled Trial

Maciej Kaszyński; Dorota Lewandowska; Piotr Sawicki; Piotr Wojcieszak; Izabela Pągowska-Klimek

Disclosures

BMC Anesthesiol. 2021;21(2) 

In This Article

Methods

Study Design

The study was conducted in a single teaching hospital – the University Clinical Centre of the Medical University of Warsaw.

In this single-blind, randomized controlled trial, children were randomly assigned to two groups according to the use of intraoperative intravenous lidocaine infusions to compare the requirement for opioids during and after laparoscopic appendectomy. Sevoflurane consumption, time to the first nalbuphine dose, incidence of postoperative nausea and vomiting and side effects were also assessed. The study was conducted between March 2019 and January 2020. Patients were enrolled between 26/03/2019 and 15/01/2020.

In accordance with the current Polish law and Declaration of Helsinki the study was approved by the Ethics Committee of the Medical University of Warsaw (KB/24/2019).

The trial was registered at the US National Institutes of Health (ClinicalTrials.gov): NCT03886896. The date of registration: 15/03/2019.

Study Population

Children presenting for laparoscopic appendectomy to be anesthetized by the physicians involved in the study were assessed for eligibility criteria.

The inclusion criteria are listed below:

Age between 18 months and 18 years;
ASA physical status class 1E, 2E, 3E;
Patients undergoing laparoscopic appendectomy.

The exclusion criteria are listed below:

Allergy to local anesthetics or contraindications for the use of lidocaine;
ASA physical status class 4E or higher;
Severe cardiovascular disease;
Preoperative bradycardia;
Preoperative atrioventricular block;
Renal failure;
Chronic treatment with analgesics;
Legal guardians' refusal.

Researchers spoke to the parents or legal guardians and informed them about the study. They described the potential risks and benefits of the procedure, discussed questions and concerns, and then obtained written informed consent.

Study Interventions

The enrolment team consisted of three physicians. Only patients operated on during their shifts were evaluated for eligibility criteria (Figure 1). The other patients were labelled "Not available for the study team". Participants were randomly assigned to one of two groups.

Figure 1.

Study flowchart

Patients in the experimental arm received intravenous lidocaine bolus of 1.5 mg/kg over 5 min before induction of anesthesia followed by lidocaine infusion at 1.5 mg/kg/h intraoperatively. The infusion was discontinued before the patients' transfer to the postanesthesia care unit (PACU).

Patients in the control arm received no additional treatment.

Other than the studied intervention, both groups of participants were treated according to the same fixed perioperative care protocol.

Anesthesia Protocol Description. The peripheral intravenous catheter was inserted in the Emergency Room or in the Surgery Ward when obtaining blood samples. Topical local anesthetics were not used.

Due to the principal diagnosis – acute appendicitis, all of the cases were classified as emergencies (E).

The decision to perform rapid sequence intubation with a high dose of rocuronium was made after individual evaluation based on anamnesis and physical examination carried out by the anesthesiologist. Meeting preoperative fasting recommendations (intervals of 6, 4, and 2 h of fasting for solids, breast milk, and clear fluids, respectively) was one of the factors taken into account in the assessment of the risk of aspiration, but due to the nature of acute abdomen it was of minor importance. Cricoid pressure (Sellick Maneuver) was not utilized.

Upon admission to the operating wing, IV midazolam at 0.05 mg/kg was administered for premedication. The patient was then transferred to the operating theatre, where their vital signs were captured. In the lidocaine group, the loading dose of lidocaine was administered.

Induction of anesthesia was achieved with IV propofol 4 mg/kg, fentanyl 3 μg/kg and rocuronium 0.6–1.2 mg/kg. Intravenous infusion of lidocaine was started in the participants concerned. The second dose of 2 μg/kg fentanyl was administered before skin incision. While under anesthesia, patients were also given acetaminophen 15 mg/kg and metamizole 10 mg/kg. Anesthesia was maintained with sevoflurane. Additional fentanyl doses of 1μg/kg were given when the heart rate or blood pressure exceeded 20% of baseline readings. The minimal alveolar concentration of sevoflurane was titrated to maintain the bispectral index (BIS) in the 40–45 range. A fixed protocol of fresh gas flow (FGF) was utilized. The initial FGF during induction and the first 5 min after intubation was 6 L/min, subsequently reduced to 3 L/min until the vaporizer was closed. The consumption of air and oxygen was used to asses adherence to protocol.

Heart rate, blood pressure, peripheral oxygen saturation (SpO2), BIS, BIS signal quality index (SQI) and electromyography (EMG), total anesthetic gases and anesthetic agent consumption were recorded and archived in the study database. Electrocardiogram, end-tidal carbon dioxide tension, end-expired sevoflurane concentration, gas flow, oxygen concentration, peak and mean airway pressures were monitored as well, however, due to technical limitations, these parameters could not be transferred directly to the database, and some have been archived as photos.

If laparoscopy was converted to open surgery, data collection was discontinued, but pain management strategy was not changed.

After surgery, the children were extubated and transferred to the PACU.

In the PACU, patient monitoring included the heart rate, blood pressure, peripheral oxygen saturation (SpO2), pain, sedation score, nausea and vomiting (Table 1).

Postoperative pain was assessed using common scales: FLACC (Face – Legs – Activity – Crying – Consolability Scale), NRS (Numerical Rating Scale), or VAS (Visual Analog Scale for pain), depending on the participant's age and compatibility. When the pain score exceeded 3, nalbuphine titration with an initial dose of 0.1 mg/kg was commenced.

In the surgery ward, non-opioid analgesics were administered on a scheduled around-the-clock (ATC) basis (acetaminophen 15 mg/kg every 6 h and metamizole 10 mg/kg every 8 h). Postoperative pain was assessed every 4–6 h, and on patients' demand. The nalbuphine dose established previously by titration was administered when the pain score exceeded 3. Incidences of PONV were observed and treated with ondansetron 0.1 mg/kg if necessary.

Randomization

The eligible children were assigned to groups according to a computer-generated permuted block randomization list prepared by a statistician with no clinical involvement in the trial.

The size of each block was six. Study allocation ratio was 1:1. Information about the participant's allocation was concealed in a sealed envelope.

During the informed consent process, the researchers, attending anesthesia teams and the children's families were blinded to treatment allocation. After the consent had been obtained, the investigator opened the envelope. The study drug was prepared by a nurse.

Throughout the study, all medication was administered to randomized patients according to their allocation.

The attending care team at the PACU was not informed about the patients' treatment allocation, but information about the drugs administered during anesthesia (including lidocaine) was accessible in medical records.

The attending team at the surgery ward was not informed about the patients' participation in the study prior to one of the researchers coming to the ward to collect the data from medical records (at least 24 h after surgery). No additional information sheet about the patients' inclusion was attached to medical records. Written information about the trial and the consent forms were given to the participants' parents or legal guardians, and these were not part of medical documentation. Participants and their families were not informed about the allocation unless they asked.

Study outcomes

Data were collected in three settings:

  1. Operating theatre (OT) by the anesthetist – one of researchers;

  2. PACU by one of the researchers if available, or by a regular PACU staff member;

  3. Surgical ward (SW) by local nurses.

The primary outcome was postoperative opioid consumption in the first 24 h after removal of the endotracheal tube. Total nalbuphine requirement in milligrams per kilogram body weight was assessed. Data were collected from the patients' regular medical records.

The secondary outcomes of this study were:

  1. The requirement for opioids during anesthesia – assessed by measuring the total amount of fentanyl in micrograms per kilogram body weight used from the induction of anesthesia through to PACU admission.

  2. The requirement for volatile anesthetics – assessed by measuring the amount of sevoflurane in milliliters used during anesthesia.

  3. Time to first perception of significant pain (time to first rescue analgesic request – defined as pain score > 3 points) – the time to the first dose of nalbuphine that was administered.

  4. Incidence of postoperative nausea and vomiting (PONV) in the first 24 h after removal of the endotracheal tube – a four-point ordinal scale was utilized (Table 1).

  5. Side effects of lidocaine – assessed by recording the rates of the following complications: arrythmia, hypotension (defined as <70th percentile for age), light-headedness, tinnitus, perioral numbness, during anesthesia and 24 h after removal of the endotracheal tube.

There were no amendments to the study protocol after the commencement of the study.

Sample Size and Statistical Analysis

Determination of sample size requirement was based on the data available from the study by Lauwick.[9] To detect a minimum 25% reduction in opioid requirement in the postoperative period, with a type-1 error of 0.05 and a power of 80%, the study required 32 subjects in each group.

We allowed for a 15% rate of children lost to follow-up due to conversion to open surgery, need for opioid rotation, incomplete medical records, and other reasons. The final recruitment target of 74 was split into two cohorts of 37 patients each.

Categorical data are expressed as the number of participants and the corresponding percentage of the group. Differences between the proportions of qualitative data were assessed with the χ2 test. Quantitative data were assessed for normal distribution using the Shapiro-Wilk test. Normally distributed data are expressed as mean (SD) and Student's t-test was used for inter-group comparison. Non-parametric data are reported as median (interquartile range – IQR) and were compared using the Mann-Whitney U test. A p-value < 0.05 was considered to be statistically significant. All analyses were conducted using the Statistica software version 13.1 (Statsoft Co.).

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