Tranexamic Acid for Traumatic Injury in the Emergency Setting: A Systematic Review and Bias-Adjusted Meta-Analysis of Randomized Controlled Trials.

STUDY OBJECTIVE: Traumatic injury causes a significant number of deaths due to bleeding. Tranexamic acid (TXA), an antifibrinolytic agent, can reduce bleeding in traumatic injuries and potentially enhance outcomes. Previous reviews suggested potential TXA benefits but did not consider the latest trials. METHODS: A systematic review and bias-adjusted meta-analysis were performed to assess TXA's effectiveness in emergency traumatic injury settings by pooling estimates from randomized controlled trials. Researchers searched Medline, Embase, and Cochrane Central for randomized controlled trials comparing TXA's effects to a placebo in emergency trauma cases. The primary endpoint was 1-month mortality. The methodological quality of the trials underwent assessment using the MASTER scale, and the meta-analysis applied the quality-effects method to adjust for methodological quality. RESULTS: Seven randomized controlled trials met the set criteria. This meta-analysis indicated an 11% decrease in the death risk at 1 month after TXA use (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.84 to 0.95) with a number needed to treat of 61 to avoid 1 additional death. The meta-analysis also revealed reduced 24-hour mortality (OR 0.76, 95% CI 0.65 to 0.88) for TXA. No compelling evidence of increased vascular occlusive events emerged (OR 0.96, 95% CI 0.73 to 1.27). Subgroup analyses highlighted TXA's effectiveness in general trauma versus traumatic brain injury and survival advantages when administered out-of-hospital versus inhospital. CONCLUSIONS: This synthesis demonstrates that TXA use for trauma in emergencies leads to a reduction in 1-month mortality, with no significant evidence of problematic vascular occlusive events. Administering TXA in the out-of-hospital setting is associated with reduced mortality compared to inhospital administration, and less mortality with TXA in systemic trauma is noted compared with traumatic brain injury specifically.

Crystalloid Fluid Management of Non-Traumatic Hypotension by New South Wales Ambulance.

INTRODUCTION: Shock is circulatory insufficiency, inadequate oxygen delivery, and cellular hypoxia. Intravenous fluids are essential for shock management. Despite treatment, patients can face persistent shock with ongoing hypotension, contributing to higher mortality. This analysis aims to quantify hypotensive non-traumatic cases in an Australian ambulance service, determine persistent hypotension prevalence, and assess paramedic-administered intravascular fluids' impact on blood pressure changes. METHODS: This study is a retrospective analysis of prehospital fluid resuscitation by New South Wales Ambulance paramedics during 2022. Hypotension is defined as a systolic blood pressure of ≤ 90 mmHg, and persistent hypotension is a systolic blood pressure consistently below 90 mmHg across all observations, with a final blood pressure below 90 mmHg. This study aimed to determine the volume of fluid resuscitation at which a plateau in population-level systolic blood pressure response is observed, by calculating the derivative of the fitted logistic regression model. Moreover, this analysis identified the relative contribution of factors influencing the probability of an attempt at intravenous or intraosseous access using machine learning. RESULTS: Among 796,865 attendances, 23,049 (2.9%) involved non-traumatic patients with hypotension. In total 7,388 (32.1%) of the hypotensive cases resulted in persistent hypotension, of which 3,235 (43.8%) received Hartmann's solution and 1,745 (53.9%) received at least 500 ml of fluids but still had hypotension. The model showed that systolic blood pressure tends to stop increasing after 500-600 milliliters of fluid are given. This suggests that, on average, giving more fluid than this may not raise blood pressure further in a prehospital setting, though individual patient needs can differ. The top four factors from the machine learning shows that as initial respiratory rate goes up, the probability of intravascular access rises. Transport times less than 20 min are associated with a smaller chance of access and younger patients are less likely to receive an attempt. Finally, extremes of systolic blood pressure are more likely to receive access attempts. CONCLUSION: This study found that three percent of non-traumatic attendances have at least one episode of hypotension, and that more than half of these have persistent hypotension. Only 44% of persistently hypotensive received fluids, and half of persistently hypotensive patients stayed hypotensive despite a reasonable volume of prehospital crystalloids.

Temporal changes in blood pressure following prehospital rapid sequence intubation.

BACKGROUND: Rapid Sequence intubation (RSI) is an airway procedure that uses sedative and paralytic drugs to facilitate endotracheal intubation. It is known that RSI could impact blood pressure in the peri-intubation period. However, little is known about blood pressure changes in longer time frames. Therefore, this analysis aims to describe the changes in systolic blood pressure in a large cohort of paramedic-led RSI cases over the whole prehospital timespan. METHODS: Intensive Care Paramedics in Victoria, Australia, are authorised to use RSI in medical or trauma patients with a Glasgow Coma Scale <10. This retrospective cohort study analysed data from patientcare records for patients aged 12 years and above that had received RSI, from 1 January 2008 to 31 December 2019. This study quantifies the systolic blood pressure changes using regression with fractional polynomial terms. The analysis is further stratified by high versus Low Shock Index (LSI). The shock index is calculated by dividing pulse rate by systolic blood pressure. RESULTS: During the study period RSI was used in 8613 patients. The median number of blood pressure measurements was 5 (IQR 3-8). Systolic blood pressure rose significantly by 3.4 mm Hg (p<0.001) and then returned to baseline in the first 5 min after intubation for LSI cases. No initial rise in blood pressure is apparent in High Shock Index (HSI) cases. Across the whole cohort, systolic blood pressure decreased by 7.1 mm Hg (95% CI 7.9 to 6.3 mm Hg; p<0.001) from the first to the last blood pressure measured. CONCLUSIONS: Our study shows that in RSI patients a small transient elevation in systolic blood pressure in the immediate postintubation period is found in LSI, but this elevation is not apparent in HSI. Blood pressure decreased over the prehospital phase in RSI patients with LSI, but increased for HSI cases.

The utility of the brain trauma evidence to inform paramedic rapid sequence intubation in out-of-hospital stroke.

BACKGROUND: Rapid sequence intubation (RSI) is used to secure the airway of stroke patients. Randomized controlled trial evidence exists to support the use of paramedic RSI for traumatic brain injury (TBI), but cannot necessarily be applied to stroke RSI because of differences between the stroke and TBI patient. To understand if the TBI evidence can be used for stroke RSI, we analysed a retrospective cohort of TBI and strokes to compare how survival is impacted differently by RSI when comparing strokes and TBI. METHODS: This study was a retrospective analysis of 10 years of in-hospital and out-of-hospital data for all stroke and TBI patients attended by Ambulance Victoria, Australia. Logistic regression predicted the survival for ischemic and haemorrhagic strokes as well as TBI. The constituents of RSI, such a medications, intubation success and time intervals were analysed against survival using interactions to asses if RSI impacts survival differently for strokes compared to TBI. RESULTS: This analysis found significant interactions in the RSI-only group for age, number of intubation attempts, atropine, fentanyl, pulse rate and perhaps scene time and time- to-RSI. Such interactions imply that RSI impact survival differently for TBI versus strokes. Additionally, no significant difference in survival for TBI was found, with a - 0.7% lesser survival for RSI compared to no-RSI; OR 0.86 (95% CI 0.67 to 1.11; p = 0.25). Survival for haemorrhagic stroke was - 14.1% less for RSI versus no-RSI; OR 0.44 (95% CI 0.33 to 0.58; p = 0.01) and was - 4.3%; OR 0.67 (95% CI 0.49 to 0.91; p = 0.01) lesser for ischemic strokes. CONCLUSIONS: Rapid sequence intubation and related factors interact with stroke and TBI, which suggests that RSI effects stroke survival in a different way from TBI. If RSI impact survival differently for strokes compared to TBI, then perhaps the TBI evidence cannot be used for stroke RSI.

The association of paramedic rapid sequence intubation and survival in out-of-hospital stroke.

INTRODUCTION: Ambulance transport of patients with stroke is common, with rapid sequence intubation (RSI) to secure the airway used regularly. Randomised controlled trial evidence exists to support the use of RSI in traumatic brain injuries (TBIs), but it is not clear whether the RSI evidence from TBI can be applied to the patient with stroke. To this end, we analysed a retrospective stroke dataset to compare survival of patients with RSI compared with patients that did not receive RSI. METHODS: This study was a retrospective analysis of 10 years of in-hospital and out-of-hospital data for all patients with stroke attended by Ambulance Victoria, in Victoria Australia. Generalised boosted logistic regression was used to predict propensity scores, with initial vital signs, age and demographic variables as well as measures of illness severity and comorbidity included in the prediction model. This analysis employed a 1:1 nearest-neighbour matching which was applied to generate a dataset from which we calculated the OR of survival to hospital discharge of patients receiving RSI versus no-RSI. The sensitivity of these results to unmeasured confounding was assessed with deterministic sensitivity analysis. RESULTS: The propensity score-matched cohort showed a decreased survival for RSI in strokes with an OR 0.61 (95% CI 0.45 to 0.82; p=0.001) when compared with no-RSI. A subgroup analysis showed no significant survival difference for ischaemic strokes: OR 0.66 (95% CI 40 to 1.07; p=0.09). The survival for haemorrhagic stroke was OR 0.60 (95% CI 0.41 to 0.90; p=0.01) lesser for RSI. Results were likely robust to unmeasured confounding and missing data. CONCLUSIONS: Our retrospective analysis shows a decrease in survival when RSI is utilised by paramedics for stroke. Since RSI is commonly used for strokes, controlled trial evidence to support this practice is urgently needed.

Survival in Out-of-hospital Rapid Sequence Intubation of Non-Traumatic Brain Pathologies.

INTRODUCTION: Rapid sequence intubation (RSI) is not only used in traumatic brain injuries in the out-of-hospital setting, but also for non-traumatic brain pathologies (NTBP) such as brain tumors, meningitis, encephalitis, hypoxic/anoxic brain injury, stroke, arteriovenous malformations, tumors, aneurysms, brain hemorrhage, as well as brain injury due to diabetes, seizures and toxicity, metabolic conditions, and alcohol and drug overdose. Previous research suggests that RSI is common in non-traumatic coma, but with an unknown prevalence of NTBP in those that receive RSI. If NTBP is common and if brain trauma RSI evidence is not valid for NTBP then a sizable proportion of NTBP receive this treatment without evidence of benefit. This study calculated the out-of-hospital NTBP prevalence in patients that had received RSI and explored factors that predicted survival. METHODS: A retrospective cohort study based on data collected from an ambulance service and seven hospitals based in Melbourne, Australia. Non-traumatic brain pathologies were defined using ICD10-AM codes for the calculation of NTBP prevalence. Logistic regression modelled out-of-hospital predictors of survival to hospital discharge after adjustment for comorbidities. RESULTS: The seven participating hospitals treated 2,277 patients that received paramedic RSI for all illnesses and indications from January 1, 2008 to December 31, 2015, with survival data available for 1,940 (85%). Of the 1,940, 1,125 (58%) patients had at least one hospital-diagnosed NTBP. Sixty-nine percent all of NTBP survived to hospital discharge, compared to 65% for traumatic intracranial injury. Strokes were the most common and had poor survival to discharge (37%) compared to the second most common NTBP toxicity/toxic encephalopathy that had very high survival (98%). No out-of-hospital clinical intervention or prehospital time interval predicted survival. Factors that did predict survival include Glasgow Coma Scale (GCS), duration of mechanical ventilation, age, ICU length of stay, and comorbidities. CONCLUSIONS: Non-traumatic brain pathologies are seven times more prevalent than traumatic brain injuries in patients that underwent out-of-hospital RSI in Victoria, Australia. Since the mechanisms through which RSI impacts mortality might differ between traumatic brain injuries and NTBP, and given that NTBP is very prevalent, it follows that the use of RSI in NTBP could be unsupported.

Evaluating the effectiveness of the maximum permitted dose of midazolam in seizure termination: Insights from New South Wales, Australia.

OBJECTIVE: Out-of-hospital seizures demand rapid management. Midazolam plays a key role in stopping seizures. At times the first dose of midazolam proves insufficient, necessitating additional doses. Within the New South Wales Ambulance (NSWA) service, the upper limit for midazolam administration is set at 15 mg. However, the outcomes and safety of using midazolam at this maximum dosage have not been thoroughly investigated. METHODS: A retrospective analysis of out of hospital electronic health records from New South Wales, Australia, over the year 2022, was conducted. The study manually reviewed cases where adult patients received the maximum dose of midazolam for seizure management by paramedics. It focused on seizure cessation success rates and the incidence of adverse effects to evaluate the clinical implications of high-dose midazolam administration. RESULTS: Of 818 790 individual attendances by NSWA clinicians, a total of 11 392 (1.4%) adults had seizures noted, of which midazolam was administered in 2565 (22.5%). An algorithm shows that in 2352 (91.7%) instances the midazolam was associated with the apparent termination of seizures. Analysis revealed that 176 (1.5%) proportion of all adult's seizure patients required the maximum dose of midazolam for seizure control. These higher doses successfully terminate seizures in about half of the instances. AEs following the maximum dose of midazolam included hypoxia in 26.7% of patients and respiratory depression in 9.7%, indicating significant side effects at higher dosages. CONCLUSION: In New South Wales, Australia, administering the maximum dose of midazolam to seizure patients is rare but proves effective in approximately half of the refractory seizure cases. Therefore, assessing the potential for additional doses of midazolam or the use of a second-line agent is advisable.

Physician presence at out-of-hospital cardiac arrest is not necessarily the cause of improved survival.

A recent publication Hiltunen et al. on Out-of-Hospital Cardiac Arrest (OHCA) in Finland show increased survival when a physician attends an OHCA, compared to EMS. But it is likely that physicians attend OHCA patients with a different prognosis due to comorbidity or illness severity, which causes confounding by indication and is the likely cause for the physician and survival association.