Pain assessment must be performed before, during, and after a painful procedure, and also 30 minutes after an analgesic intervention, and it must be objective and performed regularly using a validated tool^6,7 such as the following: Visual Analogue Scale (VAS), in patients over 8 years of age⁸; Verbal Numeric Scale (VNS), in patients over 12 years of age and in settings where there is limited understanding of the VAS⁸; Verbal Global Scale (VGS), in patients over 12 and in settings where there is limited understanding of the VAS and the VNS⁸; Smiles Pain Rating Scale (SRPS), in patients 5 to 12 years of age⁸; FLACC (pain facies, lower limb movements, agitation, consolabilty, and crying), in children under 5 years of age.⁸

Potent opioid drugs are the cornerstone in the management of acute pain due to burn injuries.^8-11 It is suggested to initiate management with potent opioid drugs and then taper down, instead of scaling up in potency.^9,12 Every service in which these drugs are used routinely must have access to oxygen sources, devices, and trained staff for cardiopulmonary cerebral (CPCR) resuscitation, and naloxone.^8-10 In addition, side effects from opioid administration must be anticipated and treated aggressively.^9-11,13 Extremely painful procedures or procedures that cannot be tolerated by the patient must be performed under general anaesthesia.^9,10,12,14

It is advisable to give all patients a scheduled around-the-clock (ATC) prescription of paracetamol 500 mg p.o. every 6 hours in adults, and 10 to 15mg/kg every 6 hours in children^8,10,11,14 as part of underlying pain management, unless contraindicated.^10,11 Adding an ATC short-cycle (maximum 3 days) prescription of nonsteoridal anti-inflammatory agents (NSAIDs) may be considered^12,13 (ibuprofen 400 mg Per Os (PO) every 8 hours, 10 mg/kg every 8hours in children over 6 months of age, or diclofenac 50 mg PO every 12hours, 75 mg IV every 12hours in adults, 1 to 2 mg/kg every 12 hours in children over 5 years of age), and ATC paracetamol in noncritically ill patients with preserved oral route during the acute burn phase.⁹

Should pain control not be achieved with the administration of paracetamol or a short cycle of NSAIDs, a weak opioid agonist should be added ATC to the pharmacological regimen, including tramadol 1 mg/kg/dose every 6 to 8 hours in children or 50 to 100 mg Intravenous (IV) every 6 to 8hours maximum 400mg/day in adults, or codeine 1 mg/kg/dose every 6 to 8hours in children, or 30 to 60 mg PO every 6 hours in adults, maximum 240mg/day.^6,7,9,15

If these measures are not sufficient to achieve adequate pain control, pharmacological management with a scheduled strong opioid agonist should be initiated, making sure that the weak opioid administration is discontinued first, as follows: low-dose intravenous morphine titration (1-2 mg in adults, 0.01 mg/kg in children) every 5 to 10 minutes until pain control is achieved or until the patient is drowsy, titrating the whole dose every 4 to 6 hours if persistence of the cause of pain is anticipated.^9,16,17

If no strong opioid is available, ATC administration of an agonist-antagonist opioid-like nalbuphine 0.4mg/kg/dose every 4 to 6 hours may be prescribed instead of the weak opioid.¹⁷

Another management option for acute pain is patient-controlled analgesia (PCA), which is mainly useful for incident pain management. PCA with fentanyl is recommended using 1 initial bolus of 1 mg/kg, 30 mg on demand, with 5-minute closure interval, or intravenous morphine 0.05 to 0.2 mg/kg/dose every 4 to 6 hours.⁷ Also useful in the management of incident pain is meperidine 1 mg/kg/dose (maximum 4 doses in total).¹⁶

There are several options with high-quality evidence for the management of pain caused by procedures in this population. The first is the application of a strong opioid before the procedure (morphine 0.05-0.2 mg/kg 10 minutes before, or fentanyl 1 mg/kg 5 minutes before) or the use of PCA associated with a benzodiazepine before the procedure (midazolam 0.05 mg/kg 30minutes-1hour be-fore).^{6,7,12,14,18,19} The association with ketamine has been used widely for more than 40 years in burn patients, but its use has diminished because of the side effects, which can be avoided when used together with a benzodiazepine. Ketamine at a dose of 1 mg/kg associated with a benzodiazepine (midazolam 0.05 mg/kg) and an antisia-lagogue (atropine 0.01mg/kg) is an excellent analgesic option, provided it is administered in centers where the anesthetist is present.^{6,8,14,15,19-21}

Another combination of drugs that offers excellent analgesic effect for procedure-associated pain is dexmedetomidine in a 1 mg/kg bolus, associated with a bolus dose of ketamine 2 mg/kg and tramadol 1 mg/kg, in intermediate care facilities, with presence of staff trained in CPCR or of the anaesthetist.^10,20,22,23

On the contrary, nonpharmacological interventions in adolescents include the association of virtual reality, performed in facilities with the appropriate infrastructure and duly trained personnel,^{6,13,18,24-29} as well as the use of transcutaneous electrical stimulation (TENS), before, during, and after the procedure. These interventions need to be explained to the patient and used in association with pharmacological regimens.^19,30

The plastic surgery anesthesia service should think about using preventive systemic analgesia with NSAIDs or systemic paracetamol before the procedure,^16,19 and tumescent anaesthesia,⁶ regional blocks,^{6,13,14,18,21} or topical lidocaine for dressing changes^6,8,15 in an attempt at providing residual analgesic effect after the surgical-anesthetic procedure. In stable patients who tolerate well the oral route, the use of weak opioids can be considered, including codeine at a dose of 30 to 60 mg every 6hours and a maximum dose of 240mg/day, maintaining active vigilance on side effects in order to treat them promptly. The use of conventional oxycodone at a dose of 5 to 10 mg every 8 hours or with an extended release formula every 12 to 24hours, methadone 2.5 to 5mg every 6hours, or hydrocodone 5 to 10mg every 4 to 6hours may also be considered. It is important to try not to use oral opioids for more than 10 days in order to avoid physical dependence.^6,8,18,19,31

Given the characteristics of the injuries in burn patients, neuropathic pain is common in this population. Consequently, the early association of pregabalin is recommended on the basis of proven clinical effectiveness in reducing peripheral and central neuropathic pain at a starting titration of 37.5 mg with oral opioid.^19,32-34 In situations where there is no access to pregabalin, the use of gabapentin should be considered, at an initial titration of 300mg PO per day.^33,35,36

Pruritus must be treated with pharmacological measures such as gabapentin in incremental doses, from 300 mg up to 1500mg/day PO^37-42 and also with nonpharmacological measures proven to be effective,^37,40 bearing in mind that the oral route may be used for administering medications in cases of mild burns,^11,43 and that the intramuscular and subcutaneous routes should not be used in the acute phase of the burn injury.^6,43

Nonpharmacological options should be offered together with pharmacological ones.^9,10,21,31 In services with the adequate facilities and trained personnel, nonpharmacological strategies may include music therapy, hypnosis, nonimmersive virtual reality (images, videos, video games) or immersive virtual reality, and psychotherapy before and after any procedure, and throughout the treatment period.^10,24-28,44

The use of opioids in high doses in patients with burn injuries entails the risk of secondary adverse events. The most serious of those adverse events is respiratory depression. Recognizing or suspecting this condition early on is mandatory when faced with a patient with a confirmed history of receiving high-dose opioids, a respiratory rate lower than 8/minute, myosis, pulse oximetry below 90%, and drowsiness or stupor. Response must be immediate, priority alert must be sent to the anesthesia and emergency services, and tactile and auditory stimulation of the patient must be initiated. Naloxone must also be titrated at a dose of 1 mg/kg IV every 3 to 5 minutes until bradypnea resolves or the patient shows signs of recovering consciousness and an arterial oxygen saturation of 91% or higher. The attending physician must determine if the patient needs basic and/or advanced airway management and ventilation in accordance with the CPCR guidelines, in which he/she must be trained. Attention must be paid to the possibility of renarcotization, depending on the opioid that caused the depression and the form of use.^{9,13,22,45-47}

In case respiratory depression secondary to the use of benzodiazepines is suspected, the administration of flumazenil 0.2 mg IV every minute is recommended until the patient regains consciousness, followed by the steps described above under the heading on management of opioid-related respiratory depression.^8,22,48,49

In the event of altered sensory perception (hallucinations, delusions) or behavior (agitation, inattention) suspected to be related to the use of ketamine, the emergency anesthesia service should be notified immediately while simultaneously initiating midazolam at a dose of 0.05 mg/kg.^22,49,50

Whenever an opioid withdrawal syndrome is suspected, active support from the Pain Clinic and the psychology and psychiatry services of the institution must be requested.

Withdrawal syndrome in patients managed with strong opioids in the Burn Unit (step-down unit) or the Intensive Care Unit must be suspected in the presence of suggestive symptoms such as tachycardia, diaphoresis, hypertension, mydriasis, piloerection, muscle cramps, abdominal cramps, or diarrhea. Weaning from potent opioids is suggested if they have been used for more than 5 days, tapering the dose initially by 20% to 40%, followed by subsequent 10% reductions every 12 to 24hours.^51-54

In the presence of physical findings of opioid withdrawal when strong opioids have been used for more than 10 days, the initiation of substitution therapy with metha-done at a fractionated equianalgesic dose every 6 to 8 hours can be considered, tapering it down by 20% every week until complete discontinuation is achieved towards the fifth week.^51,55

The concomitant use of nonsubstitution therapy (ben-zodiazepines, clonidine) is suggested.^54-56