This was a single-center observational study. We completed this study between December 2022 and June 2023 in the major burn center of Hospital Antonio Cardarelli (Naples, Italy). This study was approved by the local institutional review board (Ethics Committee 11/22 of 29 September 2022) and conducted according to the Declaration of Helsinki. All subjects provided informed consent to participate in the study. All participants provided consent for publication.

Patients presenting with second- and third-degree burns based on depth and at least 30% of the total body surface area (TBSA) were enrolled in the emergency department. Only patients with a Glasgow Coma Scale (GCS) > 13 and not intubated were included. We included only patients > 18 years of age who were able to provide written informed consent.

Patients were excluded if they met any of the following criteria: first- or fourth-degree burns based on depth or < 30% of TBSA, GCS < 12, patients needing mechanical ventilation, other non-medical intervention/therapy for the treatment of pain, liver, kidney or heart failure, contraindications to the drugs to be tested (e.g., NSAIDS, opioids) and women who were breastfeeding or pregnant (excluded from medical history and/or laboratory tests).

According to the American Burn Association, there are five burn categories based on burn depth: superficial (first degree), superficial partial-thickness or deep partial-thickness (second degree), full thickness (third degree) and deep full-thickness (fourth degree) [11]. Fourth-degree burns are generally painless, and therefore they were excluded from our study.

According to the percentage of total body surface area burned, patients with TBSA < 15% are considered minor in severity, those with TBSA between 15% and 25% are moderate, and those with TBSA > 25% are major [12].

After an immediate assessment to determine patients’ status, patients were placed on a cardiac monitor, pulse oximeter and blood pressure monitor. Blood samples, arterial gas analysis and microbiological swabs were routinely performed. Supplemental oxygen therapy was initiated to ensure oxygen saturation > 94%. After central venous line placement, an intravenous infusion of 4 ml/kg/TBSA of lactated Ringer's was started according to the Parkland formula [13]. The first half of this volume was delivered within 8 h of the accident, while the second half was delivered within the following 16 h. When trauma was reported, the patient underwent a total body computed tomography (CT) scan. All patients were evaluated by a plastic surgeon to assess burn extension and depth.

Pain intensity was assessed using Numerical Rating Scale (NRS) at ED admission and after 1 h. The Burn Specific Pain Anxiety Scale (BSPAS) was performed at ED admission and after 1 h. BSPAS is a self-report anxiety assessment tool that evaluates anxiety symptoms [14]. Each of the 33 items is rated on a scale of 0–3, where 0 indicates that the patient was not bothered, while 3 indicates that the patient was actually very bothered by the feeling, thought or symptom described.

Pain medications administered before arrival in the ED were reported by the rescue team.

All patients received IV acetaminophen every 8 h. Intravenous morphine was administered under close monitoring and carefully titrated for each patient, as IV morphine requirements show marked inter-patient variability. The dose of IV morphine was 2–3 mg (titrate at intervals not < 5 min if NRS ≥ 4). Adverse events were recorded.

During observation in the ED, IV midazolam was administered to control agitation according to BSPAS.

All patients were transferred to our major burn center.

The primary outcome was to evaluate the efficacy of IV morphine for management of burn pain in the ED; this was assessed in terms of decreases in NRS and BSPAS. Secondary outcomes were to evaluate the incidence of adverse effects following IV morphine administration and pain management in the pre-hospital setting.

Data were analyzed using a standard computer program (Excel, 2016). Results are reported as mean ± standard deviation (SD). We tested the consistency of our data using chi-square test and 95% confidence level. Comparisons were performed using Student's t-test, and the level of statistical significance was p < 0.05.