Authors: Keiran O’Mahony, James Mercer, Sophie Mohun Kemp, Catherine Davies, Govind Oliver / Editors: Rajesh Chatha, Robert Hirst / Codes: MuP1, MuP2, ObP1, OptP4, ResP1, RP4, SLO1 / Published: 15/07/2021

Happy TERNSday! The aim of TERN Top Papers is to highlight the top emergency care related papers for emergency physicians, keeping them abreast of the latest practice-changing studies. This month’s Top Papers comes from the beautiful hills of Snowdonia, with the team from Bangor Emergency Department bringing you this month’s summary of important articles for your attention. Our writing team is a mixture of EM trainees, clinical fellows and an advanced practitioner so brings a variety of perspectives. This month we covered the topics of analgesia and sedation. With just under 1,000 articles reviewed, we found it hard to settle on our final selection but these are the six that caught our eye.


Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED) Study: A Randomized Controlled Trial of Methoxyflurane Versus Standard Care 1

It is extremely likely that you have come across a representative extolling the analgesic benefits of methoxyflurane. Your Emergency Department (ED), like many others, may be converts. Should we all be?

This is an Australian single centre open-label randomised trial comparing 3mL of methoxyflurane to standard analgesic treatment at triage for adult patients (18-75 years) in the ED with severe pain. Patients with a pain score of ≥ 8 on the 11-point Numerical Rating Scale (NRS) were included with a primary outcome of a ≥50% drop in the pain score at 30 minutes. They also looked at the proportion of patients achieving a >2-point reduction on the NRS at multiple time points. Importantly, unlike much of the previous evidence relating to methoxyflurane, pain was not limited to that caused by trauma and injury.

120 patients were included with 60 receiving methoxyflurane and 60 standard care (paracetamol, NSAID, tramadol, oxycodone PO and morphine IV). There was no significant difference in the primary outcome between methoxyflurane and standard care with 6 (10%) and 3 (5%) patients achieving a ≥50% reduction in their pain score at 30 minutes. However, a higher proportion of patients reported a >2-point drop on the NRS at all time points in the methoxyflurane arm: 17% vs. 5% at 15 minutes, 25% vs. 9% at 30 minutes, 30% vs. 10% at 60 minutes, and 33% vs. 13% at 90 minutes.

The key limitations have been highlighted by Bond et al.2 There is potential for bias towards methoxyflurane due to the lack of blinding although pragmatically this would be difficult to achieve. The study population may not be representative of our patients with only 4% of patients included arriving by ambulance. The exclusion of patients with abnormal vital signs (inc. HR >140 or RR >36) potentially removes an interesting cohort from the study where derangements could be due to severe pain.

Bottom Line

Whist no significant difference was observed in the primary outcome, a clinically significant lower pain score was achieved in patients who received methoxyflurane compared to standard care.


  1. Brichko L, Gaddam R, Roman C, O’Reilly G, Luckhoff C, Jennings P, Smit V, Cameron P, Mitra B. Rapid Administration of Methoxyflurane to Patients in the Emergency Department (RAMPED) Study: A Randomized Controlled Trial of Methoxyflurane Versus Standard Care. Acad Emerg Med. 2021 Feb;28(2):164-171. doi: 10.1111/acem.14144. Epub 2020 Oct 28. PMID: 32989888.
  2. Bond C, Westafer L, Challen K, Milne WK. Hot off the press: the RAMPED trial-methoxyflurane for analgesia in the emergency department. Acad Emerg Med. 2021 Mar 26. doi: 10.1111/acem.14257. Epub ahead of print. PMID: 33772948.
Is ketamine sedation without local anaesthesia sufficient for pediatric laceration repair? A double-blind randomized clinical trial.3

Ketamine is a dissociative anaesthetic, potent analgesic and amnesic which is often used for paediatric sedation in the ED.

This prospective, randomized, double-blind study aimed to assess whether ketamine sedation without local anaesthesia provided sufficient analgesia in paediatric patients undergoing laceration repair. It was a single-centre trial conducted in a tertiary care paediatric emergency department in South Korea. Participants were randomised to receive either local lidocaine anaesthesia with ketamine sedation (control group) or local normal saline injection with ketamine sedation (study group).

The primary outcome was pain scores (measured using the Children’s Hospital of Eastern Ontario Pain Scale) at five timepoints during the procedure. Secondary outcomes included Ramsay sedation scale score, physician’s satisfaction, caregiver’s satisfaction and adverse events.

The study was powered to recruit 50 participants; however, it was stopped early by the data and safety monitoring board when 47 had been enrolled as no significant difference could be determined between the two groups. The results showed no significant difference in pain scores at any of the five timepoints. No adverse events were reported and there was no significant difference in any of the other secondary outcomes.

The study had a number of limitations. It was performed at a single centre. The lacerations were small (mean wound lengths were 1.2cm in the study group and 1.14cm in the control group). A high number of 482 eligible patients were excluded prior to enrolment; 220 children were excluded due to limited numbers of research staff and another 212 declined to participate. The Ketamine dosage strategy used in the study protocol was significantly higher than is recommended in the RCEM best practice guidelines. An initial dose of 2mg/kg by slow IV injection with up to two additional 1mg/kg boluses was used in the study compared to 1mg/kg or lower by slow IV injection in RCEM Ketamine procedural sedation for children in the Emergency Department publication.


Bottom Line

With a high dose of ketamine for procedural sedation in children aged 1-10 years for wound repair, there was no reported difference in pain scores with or without additional local anaesthetic.  


3. Kwon H, Lee JH, Choi YJ, Jung JY. Is ketamine sedation without local anesthesia sufficient for pediatric laceration repair? A double-blind randomized clinical trial. Am J Emerg Med. 2021 Jun;44:208-212. doi: 10.1016/j.ajem.2020.03.030. Epub 2020 Mar 19. PMID: 32220524.

Analgesic efficacy of the serratus anterior plane block in rib fractures pain: A randomized controlled trial.4

We are well practiced in the use of fascia iliac blocks for patients with a fractured neck of femur; how about our rib fracture patients?

This prospective, single centre, randomised, non-blinded control trial looked at whether a serratus anterior plane block (SAPB) alongside patient controlled analgesia (PCA) tramadol bolus was better at managing pain from rib fractures compared to a tramadol PCA alone. Patients aged 18-90 years old who had rib fracture pain of >3 on the numerical rating scale (NRS) were enrolled. The primary outcome measure was total PCA analgesia consumption at 24 hours. Secondary outcomes were the NRS taken at regular intervals, additional analgesia requirement, peripheral oxygen saturations, chronic pain at 3 months and complications. Patients were randomised 1:1 and each received a tramadol PCA. The intervention arm also received an ultrasound guided SAPB with 30ml of 0.25% bupivacaine performed by two anaesthetists.

60 patients were enrolled with no loss to follow up. The total tramadol consumption in the SAPB group was 98.33±74.13 and 148.3±87.68 in the control group (p=0.02). The NRS was also lower in the SAPB group for all time intervals as was chronic pain at 3 months. No adverse events were reported apart from nausea and vomiting from tramadol in the control group.

Limitations of this study include the lack of blinding causing potential bias towards SAPB, although pragmatically and ethically this is reasonable. The study is set outside of the emergency department (ED) and a SAPB is currently out of the scope of practice for most emergency medicine physicians. However, being a compartment block, it has a shared skill set to an ultrasound guided fascia iliac block. Therefore, SAPB could be taught to EM physicians and used in the management of acute rib fractures in the ED.

Bottom Line

Serratus anterior plane block are effective at reducing intravenous analgesia requirement in acute rib fractures.


4. Tekşen Ş, Öksüz G, Öksüz H, Sayan M, Arslan M, Urfalıoğlu A, Gişi G, Bilal B. Analgesic efficacy of the serratus anterior plane block in rib fractures pain: A randomized controlled trial. Am J Emerg Med. 2021 Mar;41:16-20. doi: 10.1016/j.ajem.2020.12.041. Epub 2020 Dec 23. PMID: 33383266.

Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial.5

Corneal abrasions can be incredibly uncomfortable and managing the pain a challenge. This study looked at the effectiveness of tetracaine eyedrops for the treatment of pain from corneal abrasions compared to placebo.

It was a prospective randomised, double blinded control trial set in a single emergency department in the United States. It included adult patients (18 – 80 years) who presented with an acute corneal abrasion. Those excluded included contact lens wearers, previous corneal surgery, a contaminated foreign body to the eye, co-existing ocular infection, had a retained foreign body, penetrating injury or required urgent ophthalmology review.

Patients were randomised in a 1:1 ratio and either given a 2ml bottle of tetracaine 0.5% labelled ‘study drops’ or 4 separate 0.5ml ampoules of balanced artificial tears labelled identically. Both arms were also given antibiotic eyedrops and hydrocodone/acetaminophen 7.5/325mg tablets as break through. The primary outcome was overall pain measured on the numeric rating scale (NRS) at 24 to 48 hours. Secondary outcomes were the amount of break through medication taken and any adverse events. 118 people were enrolled with 59 in each arm. Seven people were lost to follow up.

At the 24 to 48-hour follow-up, the overall NRS pain score after use of the study drops was significantly lower in the tetracaine group (1 versus 8) compared with that of patients in the placebo group (difference=7; 95% CI 6 to 8; P<.001). The tetracaine group also used significantly less breakthrough medication. The number of small residual abrasion was not statistically different between the two groups. Some of the limitations in this study are that it was only powered to find a difference in pain scores, not adverse outcomes. This therefore does not disprove the old doctrine of local anaesthetic causing delayed healing or complications. However, it does show that short term use of tetracaine 0.5% is effective at treating the pain associated with corneal abrasion.

Bottom Line

Topical tetracaine 0.5% drops used in the short term are an effect treatment of the pain from simple corneal abrasions and are associated with the need for less breakthrough analgesia.


5. Shipman S, Painter K, Keuchel M, Bogie C. Short-Term Topical Tetracaine Is Highly Efficacious for the Treatment of Pain Caused by Corneal Abrasions: A Double-Blind, Randomized Clinical Trial. Ann Emerg Med. 2021 Mar;77(3):338-344. doi: 10.1016/j.annemergmed.2020.08.036. Epub 2020 Oct 27. PMID: 33121832.

Hunger Games: Impact of Fasting Guidelines for Orthopedic Procedural Sedation in the Pediatric Emergency Department 6

This paper aimed to identify if there was any increase in adverse events if current sedation guidelines were not followed for paediatric patients requiring orthopaedic procedures in the Emergency Department.

This single centre retrospective observational study included all paediatric patients requiring sedation for an orthopaedic procedure over a 7-year period. In total 2,674 patients were identified and allocated to three cohorts: those already within ASA fasting guidelines, those who were fasted in the department to meet the guidelines and those where the procedural sedation was performed outside of the guidelines. Primary outcomes were length of stay, admission to sedation time, duration of sedation and presence of adverse events.

A significant difference was identified in length of stay and time to sedation in those not fasted to ASA guidelines. In regards to adverse events, firstly they were uncommon with only 0.02% experiencing adverse events of which vomiting was the most common, although this was similar in all three fasting status groups. All other adverse events had no statistical difference. The authors do note that aspiration is very uncommon (less than 1 episode per 10,000 patients) so a study of over 20,000 sedations would be sufficiently powered to statistically demonstrate non-inferiority with regards to the adverse event of most concern regarding fasting.

There is clear potential for selection bias with this study; the factors guiding which children were sedated outside of ASA fasting guidelines were not controlled.

Bottom line

Performing orthopaedic procedural sedation in children without adhering to fasting guidelines leads to earlier sedation and discharge with no significant increase in adverse events.


6. Stewart R, Strickland C, Sawyer J, Kumar P, Gungor B, Longjohn M, Kelly D, Kink R. Hunger Games: Impact of Fasting Guidelines for Orthopedic Procedural Sedation in the Pediatric Emergency Department. Journals of Emergency Medicine. 2021 April 60. doi: 10.1016/j.jemermed.2020.10.038 PMID: 33323292

Comparison of Oral Ibuprofen and Acetaminophen with Either Analgesic Alone for Pediatric Emergency Department Patients with Acute Pain.7

Ibuprofen and acetaminophen (Paracetamol) are the two most commonly used analgesics for children who present to emergency departments (ED) with acute traumatic and non-traumatic pain. Do you give one or both?

This study looked to see whether there was a difference in pain score when combining ibuprofen and acetaminophen versus giving either alone. It was a single centre randomised, double blinded superiority trial set in a 711 bed urban community teaching hospital emergency department. It included 90 children (3-17 years) equally divided into 3 groups: 1) either ibuprofen and a placebo, 2) acetaminophen and a placebo or 3) a combination of both analgesics. Pain scores were documented using standard numeric rating scale (NRS) and FACES pain scale both pre and 60 minutes post administration. The primary outcome was a reduction in pain from initial pain scores, and secondary outcomes included rates of adverse events and the need for further analgesia after the 60 minutes. The results found that pain scores were similar across the three groups at 60 minutes, meaning they were unable to demonstrate that combining analgesics was superior to giving them alone for short term pain relief.

The key limitations include it being a single centre study with a small sample size and a short follow up period. Convenience sampling in relation to availability of research team members may have also led to some selection bias and under representation of some patients presenting out of hours. The study was underpowered to demonstrate superiority of a double analgesic strategy in comparison to a single analgesic alone and could lead to a type 2 error.

Bottom line

The combination of ibuprofen and acetaminophen versus either alone has similar outcomes for the short-term treatment of acute pain in children presenting to the ED.


7. Motov, S., Butt, M., Masoudi, A., Palacios, W., Fassassi, C., Drapkin, J., Likourezos, A., Hussain, R., Brady, J., Rothberger, N., Flom, P., Zerzna, J., and Marshall, J. (2020). Comparison of Oral Ibuprofen and Acetaminophen with Either Analgesic Alone for Pediatric Emergency Department Patients with Acute Pain. Journal of Emergency Medicine, 58, (5), 725-732.