FormalPara Key Summary Points

The management of pain following a burn is extremely complex because of the multifactorial nature of burn pain (nociceptive and neuropathic)

In the pre-hospital setting and emergency department, the main goal of acute pain management is to reduce the patients’ pain

The aim of our study was to evaluate the efficacy and adverse effects of intravenous (IV) morphine for burn pain management in the emergency department and the pre-hospital setting

IV morphine used for burn pain management in the emergency setting significantly improves patient outcomes in terms of pain intensity and reduced agitation level

Pain management in the pre-hospital setting remains difficult, and IV morphine may be considered for patients with burns presenting to the emergency department

Introduction

Burn injury is widely considered one of the most painful injuries that a person can sustain. Burn pain is one of the most difficult to treat among acute pain etiologies [1]. According to the American Burn Association Guidelines on the Management of Acute Pain in the Adult Burn Patient, the management of pain following a burn is extremely complex [2]. This is due to the multifactorial nature of burn pain, both nociceptive and neuropathic [3].

Acute pain is often poorly assessed and inadequately treated in the pre-hospital setting [4]. Many patients do not receive analgesia, often because of the lack of availability of analgesics [5].

In the emergency department (ED), the main goal of acute pain management is to reduce the patients’ pain with minimal adverse events (AEs) and allow them to maintain function. A secondary aim is to prevent the chronification of pain. Many EDs do not have pain management guidelines or pain quality management programs in place. According to different national guidelines on the provision of analgesia and sedation in emergency medicine, intravenous morphine or fentanyl is the treatment of choice for severe pain management [6, 7].

The choice of analgesic depends on severity of pain, nature of injury and local protocols. Opioids are used as first-line treatment in management of burn pain [2, 8]. They are the standard practice for pain management in most burn centers in North America and Europe, although there is great variability regarding which agents to use and how. Fentanyl is a safe and effective agent for pain control and procedural analgesia in both adults and children [2]. Morphine is widely used especially for the treatment of procedural pain [8]. Methadone appears to be a promising agent in the treatment of burn pain [2]. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDS) should be considered for all patients to decrease opioid requirements and also improve analgesia [2]. While acetaminophen has been regularly used in the treatment of burn pain because of its excellent safety profile, NASID use is limited in patients with burns because of potential adverse effects, including gastrointestinal toxicity and bleeding, renal dysfunction, risk of cardiovascular events and platelet dysfunction [2].

Pain is a major factor that exacerbates stress in critically ill patients, and burn injury is often considered one of the major conditions that cause stress [9]. Stress response to burns causes hypermetabolism, and this is associated with increased substrate turnover, cachexia and poor clinical outcomes [9]. Therefore, prevention and management of burn-induced hypermetabolism remain a clinical priority.

Pain should be assessed and treated as soon as possible. This varies depending on the severity of the pain, but ideally no more than 20–25 min should elapse between the initial pain assessment and the administration of medications [10].

Currently, the pre-hospital and ED management of acute burn pain is limited. To our knowledge, few studies have been published on the use of morphine for burn pain in the emergency setting. The aim of our study was to evaluate the efficacy and adverse effects of IV morphine for burn pain management in the emergency department. Furthermore, we wanted to evaluate pain management in the pre-hospital setting.

Methods

Study Design

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.

Patient Population

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].

Procedure

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.

Primary and Secondary Outcomes

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.

Analysis

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.

Results

From December 2022 to June 2023, 30 patients were included in this study. There were 13 men and 17 women, with an average age of 53 (47–64) years. Nine patients reported inhalation and supplemental oxygen therapy was provided if necessary.

Twenty (67%) patients reported second- and third-degree burns, seven (23%) patients reported second-degree burns, and only three (10%) reported third-degree burns. The average burn was 38.6% TBSA in the beginning.

Demographic and clinical characteristics are reported in Table 1.

Table 1 Demographic and clinical characteristics
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As shown in Fig. 1, nine patients received IV acetaminophen or NSAIDs at the site of injury. No one received IV acetaminophen or NSAIDs during the transfer to the hospital. IV morphine was administered nine times on the site of the injury and three times during the transfer to the hospital.

Fig. 1
figure 1

Pain management at the site of injury. NSAIDs nonsteroidal anti-inflammatory drugs

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At the time of arrival to the ED, 70.8% of the patients had a NRS value of 10/10, 8.3% had 9/10 and 16.7% had 8/10, corresponding to severe pain. Only 4.2% of the patients had a NRS value of 4/10.

After the first evaluation of patients in the ED, 95.8% received IV morphine to achieve pain relief. All patients received IV acetaminophen in the ED. After 1 h, 26.1% of patients had a NRS value of 3/10 and 39.1% had a NRS value of 2/10 (p < 0.05).

Figure 2 shows the NRS trend from ED admission to 1 h from the start of treatment.

Fig. 2
figure 2

NRS at ED admission and after 1 h. NRS numerical rating scale; T_0 at time of admission; T_1h after 1 h

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The total amount of IV morphine was 18.12 ± 4.26 mg in the first hour. No adverse events were recorded.

The BSPAS on admission to the ED was 34.8 ± 5.6, indicating severe anxiety. After 1 h, BSPAS was 12.8 ± 4.8, indicating mild anxiety (p < 0.05). IV midazolam was only administered in three patients and the average amount was 3.58 ± 1.45 mg.

Discussion

In accordance with the most recent recommendations, opioids have been considered the standard of care for the treatment of acute burn pain for many years [2, 6, 7]. However, the superiority of opioids for management of burn pain has never been demonstrated. Most available data on the effectiveness and safety of opioid therapy in patients with burns comes from studies examining the use of opioids for procedural pain, especially during dressing changes [15].

To our knowledge, this is one of the few studies to assess the impact of IV morphine administration for burn pain management in ED. Morphine is a potent opioid commonly used for severe pain in the ED and pre-hospital settings. Many international guidelines recommend IV morphine as the standard analgesic for the management of severe acute pain in emergency settings [16]. Since the severity of pain is subjective, it is difficult to suggest a specific amount of morphine for pain management in the ED.

Pain control is important but difficult to manage for patients with burns, especially in the emergency setting. Patients with burns are at high risk for tolerance, possibly due to acute metabolic changes and significant changes in volume of distribution secondary to fluid loss [17]. This alters the pharmacokinetics of opioids in patients with burns.

We included patients with second- and third-degree burns, which involve the epidermis and dermis at different levels [11]. Fourth-degree burns extend through entire skin and into underlying fat, muscle and bone; they are generally painless [11]. In our study, almost all patients were treated with IV morphine, achieving good pain control in 65.2% of them 1 h after arrival in the ED. Our protocol provided the administration of IV morphine 2–3 mg at intervals of no less than 5 min in case of moderate/severe pain. All patients received IV acetaminophen, according to multimodal analgesia [6, 7]. Morphine is associated with adverse effects, such as nausea, vomiting, dizziness, respiratory depression and drowsiness [18]. According to our data, no patients showed adverse events related to morphine administration.

Stress has been proven to play a role in the pathophysiology of burn pain [19, 20]. Psychological factors, such as anxiety, contribute to pain exacerbation and recurrence. Furthermore, it is known that these external factors contribute to central sensitization which is, at least in part, the process by which acute pain becomes chronic pain [20]. In our study, pain and anxiety decreased over time for patients receiving IV morphine treatment. The BSPAS showed a significant decrease, especially for the items regarding physical symptoms. Only 10% of patients received benzodiazepines. Experts suggest reserving benzodiazepines for cases of persistent agitation despite well-conducted analgesia [21]. In this case, general recommendations suggest administering IV midazolam 1–2 mg to be repeated based on the patient's response and monitoring vital signs. In conclusion, reduced anxiety levels are associated with lower pain intensity.

Except for a few patients receiving IV morphine or NSAIDS, no others received any medications until they arrived at the hospital. This was due to the difficulty of obtaining intravenous access or to the poor feeling about administering opioids in the pre-hospital setting. This is in contrast to general recommendations, which provide the administration of acetaminophen and/or NSAIDS for mild to moderate pain and opioids (morphine, fentanyl or sufentanil) for severe pain [7].

Limitations

Our study has several limitations. First, this was a single-center study. Second, owing to the small number of burn subjects, our results have insufficient power to convincingly reveal the potential treatment effects of morphine on burn pain in emergency setting. Third, different time intervals between drug administration and first pain score, whether multiple drugs were administered (e.g. NSAIDs and morphine), injury site, burn depth, TBSA and prior opioid use were not considered but could influence changes in pain scores. Fourth, NRS was not assessed at the time of drug administration in the pre-hospital setting for organizational reasons. Finally, pain management in the pre-hospital setting is difficult to evaluate given the lack of official recommendations.

Conclusion

In conclusion, this small study demonstrated that IV morphine used for the management of burn pain in the emergency setting is potentially the ideal drug to improve patient outcomes in terms of pain. IV morphine also reduced agitation scores at 1 h. There was no increase in adverse effects when IV morphine was administered. Pain management in the pre-hospital setting remains difficult. IV morphine may be considered for patients with burns presenting to the emergency department, but larger studies are needed. Furthermore, the optimal dose of IV morphine requires further study.