Pain is the leading cause of medical consultations and occurs in 50–70% of emergency department visits. To date, several drugs have been used to manage pain. The clinical use of ketamine began in the 1960s and it immediately emerged as a manageable and safe drug for sedation and anesthesia. The analgesic properties of this drug were first reported shortly after its use; however, its psychomimetic effects have limited its use in emergency departments. Owing to the misuse and abuse of opioids in some countries worldwide, ketamine has become a versatile tool for sedation and analgesia. In this narrative review, ketamine’s role as an analgesic is discussed, with both known and new applications in various contexts (acute, chronic, and neuropathic pain), along with its strengths and weaknesses, especially in terms of psychomimetic, cardiovascular, and hepatic effects. Moreover, new scientific evidence has been reviewed on the use of additional drugs with ketamine, such as magnesium infusion for improving analgesia and clonidine for treating psychomimetic symptoms. Finally, this narrative review was refined by the experience of the Pain Group of the Italian Society of Emergency Medicine (SIMEU) in treating acute and chronic pain with acute manifestations in Italian Emergency Departments.

The availability of ultra-miniaturized pocket ultrasound devices (PUD) adds diagnostic power to the clinical examination. Information on accuracy of ultrasound with handheld units in immediate differential diagnosis in emergency department (ED) is poor. The aim of this study is to test the usefulness and accuracy of lung ultrasound (LUS) alone or combined with ultrasound of the heart and inferior vena cava (IVC) using a PUD for the differential diagnosis of acute dyspnea (AD). We included 68 patients presenting to the ED of “Maurizio Bufalini” Hospital in Cesena (Italy) for AD. All patients underwent integrated ultrasound examination (IUE) of lung-heart-IVC, using PUD. The series was divided into patients with dyspnea of cardiac or non-cardiac origin. We used 2 × 2 contingency tables to analyze sensitivity, specificity, positive predictive value and negative predictive value of the three ultrasonic methods and their various combinations for the diagnosis of cardiogenic dyspnea (CD), comparing with the final diagnosis made by an independent emergency physician. LUS alone exhibited a good sensitivity (92.6%) and specificity (80.5%). The highest accuracy (90%) for the diagnosis of CD was obtained with the combination of LUS and one of the other two methods (heart or IVC). The IUE with PUD is a useful extension of the clinical examination, can be readily available at the bedside or in ambulance, requires few minutes and has a reliable diagnostic discriminant ability in the setting of AD.

Introduction Inhaled low-dose methoxyflurane is approved in Europe for emergency relief of moderate-to-severe trauma-related pain in adults, but data versus active comparators are sparse. The phase IIIb Methoxyflurane in Emergency Department in ITAly (MEDITA) trial investigated the analgesic efficacy, practicality and safety of methoxyflurane versus standard analgesic treatment (SAT) for acute trauma pain. Methods This was a randomised, active-controlled, parallel-group, open-label trial conducted in 15 Italian emergency units. Adults with limb trauma and pain score ≥ 4 on numerical rating scale (NRS) were randomised 1:1 to inhaled methoxyflurane 3 mL or SAT [intravenously administered (IV) morphine 0.1 mg/kg for severe pain (NRS ≥ 7); IV paracetamol 1 g or IV ketoprofen 100 mg for moderate pain (NRS 4–6)]. The primary endpoint was overall change in visual analogue scale (VAS) pain intensity from baseline (time of randomisation) to 3, 5 and 10 min. Non-inferiority and superiority of methoxyflurane versus SAT were concluded if the upper 95% confidence interval (CI) for the treatment comparison (methoxyflurane–SAT) was less than 1 and less than 0, respectively. Results Between 8 February 2018 and 8 February 2019, 272 patients were randomised (136 per treatment group). A total of 270 patients (mean age 51 years; 49% male; 34% with severe pain; mean baseline VAS 67 mm) were treated and analysed for efficacy and safety. Superiority of methoxyflurane was demonstrated for moderate-to-severe pain (adjusted mean treatment difference − 5.94 mm; 95% CI − 8.83, − 3.06 mm), moderate pain (− 5.97 mm; 95% CI − 9.55, − 2.39 mm) and severe pain (− 5.54 mm; 95% CI − 10.49, − 0.59 mm). Median onset of pain relief was 9 min for methoxyflurane and 15 min for SAT. Practicality of methoxyflurane treatment was rated “Excellent”, “Very Good” or “Good” by 90% of clinicians vs. 64% for SAT. Adverse events (all non-serious) were reported by 17% of methoxyflurane-treated patients and 3% of SAT-treated patients. Conclusion Methoxyflurane provided superior pain relief to SAT in patients with moderate-to-severe trauma pain and may offer a simple, fast, effective non-opioid treatment option. Trial registration Trial registered with EudraCT (2017-001565-25) on 2 March 2018 and ClinicalTrials.gov (NCT03585374) on 13 July 2018. Funding Mundipharma Pharmaceuticals S.r.l.

This systematic review examined the efficacy and safety of intranasal fentanyl (INF) for acute pain treatment in children, adults, and the elderly in prehospital emergency services (PHES) and emergency departments (ED). ClinicalTrials.gov, LILACS, PubMed, SCOPUS, EMBASE, Google Scholar and Cochrane databases were consulted until 31 December 2022. A total of 23 studies were included: 18 in children (1 PHES, 17 ED), 5 in adults (1 PHES, 4 ED) and 1 in older people (1 PHES subgroup analysis). In children, INF was effective in both settings and as effective as the comparator drugs, with no differences in adverse events (AEs); one randomised controlled trial (RCT) showed that INF was more effective than the comparator drugs. In adults, one study demonstrated the efficacy of INF in the PHES setting, one study demonstrated the efficacy of INF in the ED setting, two RCTs showed INF to be less effective than the comparator drugs and one RCT showed INF to be as effective as the comparator, with no difference in AEs reported. In older people, one study showed effective pain relief and no AEs. In summary, INF appears to be effective and safe in children and adults in PHES and ED. More high-quality studies are needed, especially in PHES and older people.

This retrospective observational study evaluated the safety and efficacy of the ketamine and dexmedetomidine combination (keta-dex) compared to ketamine or dexmedetomidine alone for sedation of patients with acute respiratory distress due to COVID-19 pneumonia who require non-invasive ventilation. The following factors were assessed: tolerance to the ventilation, sedation level on the Richmond Agitation-Sedation Scale (RASS), hemodynamic and saturation profile, adverse effects, and discontinuation or mortality during ventilation. The study included 66 patients who underwent sedation for non-invasive ventilation using keta-dex (KETA-DEX group, n = 22), ketamine (KET group, n = 22), or dexmedetomidine (DEX group, n = 22). The DEX group showed a slower sedation rate and a significant reduction in blood pressure compared to the KETA-DEX group (p < 0.05). An increase in blood pressure was recorded more frequently in the KET group. No reduction in oxygen saturation and no deaths were observed in any of the groups. None of the patients discontinued ventilation due to intolerance. The mean duration of sedation was 28.12 h. No cases of delirium were observed in any of the groups. Overall, keta-dex was associated with faster sedation rates and better hemodynamic profiles compared to dexmedetomidine alone. Keta-dex is effective and safe for sedation of uncooperative patients undergoing non-invasive ventilation.

Access to pain management is a fundamental human right for all people, including those who are at the end of life (EOL). In end-stage patients, severe and uncontrolled pain is a common cause of admission to the emergency department (ED), and its treatment is challenging due to its complex, often multifactorial genesis. The aim of this narrative review was to identify the available literature on the management of severe EOL pain in the ED. The MEDLINE, SCOPUS, EMBASE, and CENTRAL databases were searched from inception to 1 April 2023 including randomised controlled trials, observational studies, systemic or narrative reviews, case reports, and guidelines on the management of EOL pain in the ED. A total of 532 articles were identified, and 9 articles were included (5 narrative reviews, 2 retrospective studies, and 2 prospective studies). Included studies were heterogeneous on the scales used and recommended for pain assessment and the recommended treatments. No study provided evidence for a better approach for EOL patients with pain in the ED. We provide a narrative summary of the findings and a review of the management of EOL pain in clinical practice, including (i) the identification of the EOL patients and unmet palliative care needs, (ii) a multidimensional, patient-centred assessment of the type and severity of pain, (iii) a multidisciplinary approach to the management of end-of-life pain, including an overview of non-pharmacological and pharmacological techniques; and (iv) the management of special situations, including rapid acute deterioration of chronic pain, breakthrough pain, and sedative palliation.