Evaluating two doses of intravenous lidocaine infusion for relief of nerve-related pain that persists after trauma or surgery.

INTERVENTION: Intravenous lidocaine infusion, randomised to either 3 mg/kg, 5 mg/kg delivered in 30‐60 min. The attending unblinded registrar will prepare the dose as informed, cross‐checked and recorded by the pharmacist. The blinded doctor and nurse delivering the infusion will chart all information in relation to the delivery. Records from both the preparation and the delivery will be reviewed to confirm fidelity of the intervention when progressing to unblinded reporting of results. CONDITION: Peripheral neuropathic pain that persists after trauma or surgery.; ; Peripheral neuropathic pain that persists after trauma or surgery. Anaesthesiology ‐ Pain management SECONDARY OUTCOME: Average daily pain: Participant‐recorded daily on a numerical rating scale relative to pre‐infusion baseline.[Average pain recorded daily up to 12 weeks post‐infusion (extends on the primary outcome of average daily pain at 6‐8 days post‐infusion).] Current pain: Participant‐recorded daily on a numerical rating scale.[Current pain recorded daily up to 12 weeks post‐infusion.] Pain Self‐Efficacy Questionnaire (PSEQ): Participant‐reported.[PSEQ ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Brief Pain Inventory (BPI): Participant‐reported.[BPI ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Conditioned pain modulation as an indicator for descending inhibition of pain; Laboratory tested by a trained assessor with an ice‐bath for conditioned pain and a pressure algometer for the pain perception threshold.[Conditioned pain modulation ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Pharmacokinetic tests: Laboratory tests to identify the peak blood concentrations of lidocaine during the 30min infusion protocol. Four blood samples will be taken at 10min intervals, from five participants in each of the 3mg/kg and the 5mg/kg groups. These data will guide the interpretation of peak concentrations that occur when lidocaine dose is calculated by total body weight, and the validity of the dose‐response analyses.[Four blood samples for pharmacokinetic tests will be taken at 10min intervals with the 30min lidocaine infusion. ; ] Neuropathic pain questionnaire (PainDETECT): Participant‐reported.[PainDETECT ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Depression Anxiety and Stress Scale (DASS‐21): Participant‐reported.[DASS‐21 ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Number of pain paroxysms in a day: Participant‐recorded. ; [Paroxysms recorded daily up to 12 weeks post‐infusion.] Patient‐Reported Outcomes Measurement Information questionnaire (PROMIS‐29): Participant‐reported.[PROMIS‐29 ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Pain Catastrophising Scale (PCS): Participant‐reported.[PCS ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). PRIMARY OUTCOME: Safety outcome for adverse events: The objective of this outcome is to record the proportion of participants in each dosage group who demonstrate serious adverse events that require ceasing of the infusion and/or contraindicate future lidocaine infusion. Adverse events are recorded in patient charts according to standard procedures at the Tess Cramond Pain and Research Centre, from observations during and after the infusion. ; ; 1. Significantly altered level of consciousness: Consciousness will be monitored with verbal contact and physical observation during the infusion to ensure that the patient can; ‐ express mild to moderate symptoms that cause discomfort/unease, and ; ‐ communicate symptoms which herald the concerning conditions below (seizures, chest pain or large changes in blood pressure).; Loss of consciousness will be recorded along with treatment (ceasing of the infusion) and response to treatment.; ; 2. Seizures: Records will note ; ‐ Nature (type of seizure),; ‐ Duration of the seizure activity, and ; ‐ Investigations, treatment and response to treatment.; ; 3. Chest pain reflecting possible cardiac ischemia: records will note; ‐ Nature,; ‐ Location,; ‐ Intensity,; ‐ ECG changes,; ‐ Note whether cardiac arrest/death, and ; ‐ Investigations, treatment, and response to treatment.; ; 4. Severe hypertension or hypotension: This will be detected through five‐minutely observation of vital signs during the infusion. Records will note; ‐ Mean arterial pressure change of greater than 30 mmHg from baseline or 20 mmHg and the patient reporting symptom associated with hypertension/hypotension. ; ‐ Investigations, treatment and response to treatment; ; In addition to observation by the nurse and doctor during and after infusion to the time of discharge, whether any of the above symptoms are reported to have occurred in the 24 hrs following the infusion will be recorded by ; ‐ Follow‐up phone‐call by the nurse seven days post‐infusion, and ; ‐ By the researcher at Day 6‐8 sensory testing. ; Although these will be recorded, adverse events after discharge cannot be more formally assessed.; [Adverse events recorded from the time of infusion up to 6‐8 days post infusion.] Effective analgesia: Participant‐reported and defined as the proportion of participants who report at least 30% reduction in average daily pain on a numerical rating scale at the primary timepoint, relative to baseline average pain (previously recorded seven to ten days prior to infusion). ; [Effective analgesia recorded at 6‐8 days post‐infusion. This primary outcome is recorded once at this timepoint.] ; ] Temporal summation local and remote to the region of neuropathic pain as an indicator for pain wind‐up; Laboratory tested by a trained assessor with a pin‐prick stimulator.[Temporal summation ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Pain perception thresholds for thermal and pressure stimuli, local and remote to the region of neuropathic pain, as indicators for peripheral/central sensitisation (especially small fibres for thermal): Laboratory tested by a trained assessor with a thermotest unit and with a pressure algometer.[Thermal and pressure pain perception ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Peak pain (worst pain): Participant‐recorded daily on a numerical rating scale. ; [Peak pain recorded daily up to 12 weeks post‐infusion. ; ] Sensory detection thresholds for thermal stimuli, local and remote to the region of neuropathic pain as an indicator for peripheral small fibre function: Laboratory tested by a trained assessor with a thermotest unit.[Thermal sensory detection ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] Short‐form McGill Pain Questionnaire (SF‐MPQ‐2): Participant‐reported.[SF‐MPQ‐2 ; ‐ Baseline is recorded 7‐10 days prior to the lidocaine infusion. ; ‐ Second recording at 6‐8 days post‐infusion. ; ‐ Third recording at 80‐88 days post‐infusion (12 weeks). ; ] The Stanford Expectations of Treatment Scale (SETS): Participant‐reported. [SETS is recorded once within 7‐10 days prior to the lidocaine infusion. ] INCLUSION CRITERIA: The inclusion criteria are ‐ Adults with a documented diagnosis of peripheral neuropathic pain (sensory changes affecting the region of the primary pain as well as qualities identified to be indicative of neuropathic pain in the current short form of the McGill Pain Questionnaire (SF‐MPQ‐2) and the painDETECT questionnaire. ‐ Pain for at least 6 weeks duration with moderate to high intensity (average pain at least 5 and worst pain at least 7 on the numerical rating scale) and localised to one side of the body. ‐ Pain not responsive to other forms of treatment or treatment side effects with oral agents ‐ Absence of pain affecting the opposite quadrant to the primary site of neuropathic pain. This criterion excludes whole‐body pain presentations that are likely to have quite a different combination of dominant pain mechanisms and enables the opposite quadrant to be used as a pain‐free remote site for quantitative sensory testing.