Comparing restrictive versus liberal oxygen strategies for trauma patients: The TRAUMOX2 trial-Statistical analysis plan.

BACKGROUND: The international advanced trauma life support guidelines recommend that all severely injured trauma patients receive supplemental oxygen based on very limited evidence. The TRAUMOX2 trial randomises adult trauma patients to a restrictive or liberal oxygen strategy for 8 h. The primary composite outcome consists of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome). This manuscript presents the statistical analysis plan for TRAUMOX2. METHODS: Patients are randomised 1:1 in variable block sizes of four, six and eight, stratified by including centre (pre-hospital base or trauma centre) and tracheal intubation at inclusion. The trial will include 1420 patients to be able to detect a 33% relative risk reduction with the restrictive oxygen strategy of the composite primary outcome with 80% power at the 5% significance level. We will conduct modified intention-to-treat analyses on all randomised patients and per-protocol analyses for the primary composite outcome and key secondary outcomes. The primary composite outcome and two key secondary outcomes will be compared between the two allocated groups using logistic regression reported as odds ratios with 95% confidence intervals adjusted for the stratification variables as in the primary analysis. A p-value below 5% will be considered statistically significant. A Data Monitoring and Safety Committee has been established to conduct interim analyses after inclusion of 25% and 50% of the patients. CONCLUSION: This statistical analysis plan of the TRAUMOX2 trial will minimise bias and add transparency to the statistics applied in the analysis of the trial. The results will add evidence on restrictive and liberal supplemental oxygen strategies for trauma patients. TRIAL REGISTRATION: EudraCT number: 2021-000556-19; ClinicalTrials.gov identifier: NCT05146700 (date of registration: 7 December 2021).

Management of Acute Right Ventricular Failure.

PURPOSE OF REVIEW: Acute right ventricular failure (RVF) is a frequent condition associated with high morbidity and mortality. This review aims to provide a current overview of the pathophysiology, presentation, and comprehensive management of acute RVF. RECENT FINDINGS: Acute RVF is a common disease with a pathophysiology that is not completely understood. There is renewed interest in the right ventricle (RV). Some advances have been principally made in chronic right ventricular failure (e.g., pulmonary hypertension). Due to a lack of precise definition and diagnostic tools, acute RVF is poorly studied. Few advances have been made in this field. Acute RVF is a complex, frequent, and life-threatening condition with several etiologies. Transthoracic echocardiography (TTE) is the key diagnostic tool in search of the etiology. Management includes transfer to an expert center and admission to the intensive care unit (ICU) in most severe cases, etiological treatment, and general measures for RVF.

Supplemental oxygen for traumatic brain injury: A systematic review.

BACKGROUND: Oxygen supplementation is recommended after traumatic brain injury (TBI) but excessive oxygen may be harmful. The aim of this study was to investigate the effect of supplemental oxygen or high/low inspiratory oxygen fraction (FiO2 ) for TBI patients on in-hospital mortality. METHODS: We searched Medline (Pubmed), EMBASE and the Cochrane Library for interventional and observational studies fulfilling the following criteria: TBI patients >17 years (population); initial use of supplemental oxygen/high (≥0.6) FiO2 (intervention) vs no supplemental oxygen/low (<0.6) FiO2 (control) for spontaneously breathing or mechanically ventilated TBI patients, respectively with in-hospital mortality as primary outcome. Secondary outcomes were 30-day and 1-year mortality, length of stay in hospital or intensive care unit, days on mechanical ventilation, complications, and neurological impairment. RESULTS: We screened 4846 citations. Two interventional studies comparing high vs low FiO2 for mechanically ventilated TBI patients were included. No difference in in-hospital mortality was found. The first study found a statistically significant shorter length of stay in the intensive care unit for the high FiO2 -group (6.5 [4.6-11.4] vs. 11.4 [5.8-17.2] days, p = 0.02). The second study found a lower disability at 6 months in the high FiO2 -group with low disability in 25 (73.5%) vs. 15 (44.1%), moderate disability in 9 (26.5%) vs. 16 (47.1%), and severe disability in 0 (0.0%) vs. 3 (8.8%), p = 0.02. CONCLUSION: Evidence on the effect of initial use of high/low FiO2 for TBI patients on in-hospital mortality was extremely limited. Evidence on the use of supplemental oxygen for spontaneously breathing TBI patients is lacking.

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry.

BACKGROUND: Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality. METHODS: Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock). RESULTS: A total of 5912 patients were analyzed. The median age was 39 [26-55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50-0.70], p < 0.0001). CONCLUSION: In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.

Cervical Spine Clearance in Trauma Patients with an Unreliable Physical Examination.

BACKGROUND: The objective of this study was to describe and compare the timing of cervical spine clearance in trauma patients with an unreliable physical examination. METHODS: We prospectively included adult trauma patients admitted with a cervical collar and an unreliable clinical examination (as defined by the NEXUS criteria) at two level 1 trauma centers: one in the USA (US) and one in Denmark (DK). We excluded patients with cervical spine injuries requiring a collar or surgery as treatment and patients with a collar placed after hospital arrival. The primary outcome was time from emergency department (ED) arrival to collar removal. Secondary outcomes included time to CT of the cervical spine (CTCS). At the US trauma center, an institutional protocol allowing cervical spine clearance exclusively by CTCS was in place. At the Danish trauma center, cervical spine clearance was based on a clinical evaluation by an orthopedic surgeon, usually after CTCS. RESULTS: A total of 113 patients were included (US: n = 56; DK: n = 57). The median age was 47 years, and 68% were males. The main reasons for an unreliable physical examination were a Glasgow Coma Scale score below 14 (35%), distracting injuries (26%), cervical spine tenderness (13%) and intoxication (13%). The injury severity score at the US trauma center was higher than at the DK trauma center (median: 17 vs. 11, p = 0.03). Both time to CTCS (median: 41 vs. 18 min, p < 0.0001) and time to collar removal (median: 1042 vs. 49 min, p < 0.0001) were significantly greater at the US trauma center. CONCLUSIONS: Time to collar removal was significantly greater in a trauma center utilizing a cervical spine clearance protocol based on CTCS. As patients may develop complications related to the collar, future studies should clarify how early removal can be implemented without increasing the risk of morbidity.

Impact of Physician-staffed Helicopters on Pre-hospital Patient Outcomes: A systematic review.

BACKGROUND: Management of pre-hospital patients remains a challenge. In developed countries a physician-staffed helicopter emergency medical service (PS-HEMS) is used in addition to ground emergency medical service (GEMS), but the effect is debated. This systematic review aimed to evaluate the effect of PS-HEMS compared with GEMS on patient outcomes based on the published scientific literature. METHODS: Medline, EMBASE and the Cochrane Library were systematically searched on November 15, 2019 for prospective, interventional studies comparing outcomes of patients transported by either PS-HEMS or GEMS. Outcomes of interest were mortality, time to hospital and quality of life. RESULTS: The majority of 18 studies included were observational and difficult to summarize because of heterogeneity. Meta-analysis could not be carried out. Three studies found reduced mortality in patients transported by PS-HEMS compared with GEMS with Odds ratios (OR) of 0.68 (0.47-0.98); 0.29 (0.10-0.82) and 0.21 (0.06-0.73) respectively. Another two studies found improved survival with OR 1.2 (1.0-1.5) and 6.9 (1.48-32.5) in patients transported by PS-HEMS compared with GEMS. In three studies, PS-HEMS was associated with shorter time to hospital. Three studies reported quality of life and found no benefit of PS-HEMS. CONCLUSION: In this systematic review the studies comparing PS-HEMS with GEMS were difficult to summarize because of heterogeneity. We found a possible survival benefit of PS-HEMS but were unable to conduct a meta-analysis. The overall quality of evidence was low.

Ketamine for rapid sequence intubation in adult trauma patients: A retrospective observational study.

BACKGROUND: In the trauma population, ketamine is commonly used during rapid sequence induction. However, as ketamine has been associated with important side effects, this study sought to compare in-hospital mortality in trauma patients after induction with ketamine versus other induction agents. METHODS: We retrospectively identified adult trauma patients intubated in the pre-hospital phase or initially in the trauma bay at two urban level-1 trauma centers during a 2-year period using local trauma registries and medical records. In-hospital mortality was compared for patients intubated with ketamine versus other agents using logistic regression with adjustment for age, gender, Injury Severity Score (ISS), systolic blood pressure (SBP) < 90 mm Hg, and pre-hospital Glasgow Coma Scale (GCS) score. RESULTS: A total of 343 trauma patients were included with a median ISS of 25 [17-34]. The most frequently used induction agents were ketamine (36%) and propofol (36%) followed by etomidate (9%) and midazolam (5%). There was no difference in ISS or the presence of SBP <90 mm Hg according to the agent of choice, but the pre-hospital GCS score was higher for patients intubated with ketamine (median 8 vs 5, P = .001). The mortality for patients intubated with ketamine was 18% vs 27% for patients intubated with other agents (P = .14). This remained statistically insignificant in the multivariable logistic regression analysis (odds ratio 0.68 [0.33-1.41], P = .30). CONCLUSIONS: We found no statistically significant difference in mortality among patients intubated in the initial phase post-trauma with the use of ketamine compared with other agents (propofol, etomidate, or midazolam).

Spontaneous Retroperitoneal and Rectus Sheath Hemorrhage-Management, Risk Factors and Outcomes.

BACKGROUND: Spontaneous retroperitoneal and rectus sheath hemorrhage (SRRSH) is associated with high mortality in the literature, but studies on the subject are lacking. The objective of this study was to identify early predictors of the need for angiographic or surgical intervention (ASI) in patients with SRRSH and define risk factors for mortality. METHODS: We conducted a retrospective cohort study at a tertiary academic hospital. All patients with computed tomography-identified SRRSH between 2012 to 2017 were included. Exclusion criteria were age below 18 years, possible mechanical cause of SRRSH, aortic aneurysm rupture or dissection, and traumatic or iatrogenic sources of SRRSH. The primary outcome was the incidence of ASI and/or mortality. RESULTS: Of 100 patients included (median age 70 years, 52% males), 33% were transferred from another hospital, 82% patients were on therapeutic anticoagulation, and 90% had serious comorbidities. Overall mortality was 22%, but SRRSH-related mortality was only 6%. Sixteen patients underwent angiographic intervention (n = 10), surgical intervention (n = 5), or both (n = 1). Flank pain (OR 4.15, 95% CI 1.21-14.16, p = 0.023) and intravenous contrast extravasation (OR 3.89, 95% CI 1.23-12.27, p = 0.020) were independent predictors of ASI. Transfer from another hospital (OR 3.72, 95% CI 1.30-10.70, p = 0.015), age above 70 years (OR 4.24, 95% CI 1.25-14.32, p = 0.020), and systolic blood pressure below 110 mmHg at the time of diagnosis (OR 4.59, 95% CI 1.19-17.68, p = 0.027) were independent predictors of mortality. CONCLUSIONS: SRRSH is associated with high mortality but is typically not the direct cause. Most SRRSHs are self-limited and require no intervention. Pattern identification of ASI is hard.

Ketamine as a Rapid Sequence Induction Agent in the Trauma Population: A Systematic Review.

The choice of drug used to facilitate endotracheal intubation in trauma patients during rapid sequence induction (RSI) may have an impact on survival. Ketamine is commonly used in the hemodynamically unstable trauma patient although it has been associated with side effects. This review sought to investigate whether ketamine should be preferred over other induction agents for RSI in trauma patients. PubMed, Embase, and the Cochrane Library were systematically searched on September 19, 2016 for studies reporting RSI of adult trauma patients with ketamine compared with another induction agent (etomidate, propofol, thiopental, or midazolam). No language restrictions were applied. The primary outcome was 30-day mortality, and secondary outcomes included information on blood transfusions, length of hospital stay, and hospital mortality. Risk of bias was assessed using the Cochrane Risk of Bias assessment tool for randomized trials and the Risk of Bias in Non-Randomized Studies of Interventions for nonrandomized studies of intervention. A total of 4 studies were included. A cohort study from 1976 compared thiopental (n = 26) with ketamine (n = 14) for RSI in trauma patients. The primary outcome was number of blood transfusions, and no significant difference was found. Risk of bias was judged to be serious. A randomized controlled trial from 2009 compared etomidate (n = 57) with ketamine (n = 47) and found no significant difference in 28-day mortality (odds ratio [OR], 0.8 [0.4-2.0]). The trial was judged to have a low risk of bias. Two cohort studies from 2015 and 2017 also compared etomidate (n = 116 and n = 526) with ketamine (n = 145 and n = 442). No significant difference in hospital mortality between the groups was observed (OR, 1.11 [0.38-3.27] and OR, 1.41 [0.91-2.16], respectively). Both studies were judged to have a moderate risk of bias, thus excluding the possibility of a meaningful meta-analysis. The study from 2017 also reported number of units of blood transfused during the first 48 hours after trauma and length of hospital stay. No significant differences were observed (OR, 1.14 [0.87-1.49] and OR, 1.1 [0.95-1.27], respectively). Extremely few studies have compared induction agents for RSI in trauma patients. No significant differences have been found in mortality, length of hospital stay, or number of blood transfusions after induction with ketamine compared to other induction agents, but a clinically relevant benefit or harm cannot be excluded.

Dental injuries in relation to general anaesthesia-A retrospective study.

BACKGROUND: Dental injuries may occur during general anaesthesia, especially during airway management. The aim of this study was to describe cases of dental injury related to general anaesthesia, focusing on the type and extent of the injuries as well as the timing of recognition. METHOD: We reviewed the nationwide electronic database available at the Danish Patient Compensation Association and scrutinized all claims classified as possible dental injuries in relation to general anaesthesia between 2007 and 2017. RESULTS: During the 10-year study period, there were 2523 claims for compensation related to anaesthesia. Of these, 552 (21.9%) were cases of possible dental injuries following general anaesthesia. The most commonly injured teeth were the central maxillary incisors with 174 (25.3%) cases related to the left and 118 (17.2%) cases related to the right incisor. The most common injuries were fractures (41.2%) and subluxations (25.9%). Airway management included the use of Macintosh laryngoscope in 296 (64.4%) cases and a supraglottic airway device in 69 (15%) cases. Claims were more frequently approved if more than two intubation attempts were used (100% vs 82.8%, RR = 0.83, 95% CI [0.78-0.88], P = 0.0037). Injuries recognized in-hospital were more frequently approved than injuries recognized after discharge (91.6% vs 70.7%, RR = 0.83, 95% CI [0.70-0.86], P < 0.0001). CONCLUSION: The most commonly reported dental injury related to general anaesthesia in the Danish Patient Compensation Association database was a fracture. Claims were more frequently approved if more than two intubation attempts were used and if the injury was recognized in-hospital.

Supplemental oxygen and hyperoxemia in trauma patients: A prospective, observational study.

BACKGROUND: Supplemental oxygen is recommended during the initial treatment of trauma patients according to several guidelines, but the supporting evidence is sparse. We aimed to describe the use of supplemental oxygen and occurrence of hyperoxemia in the initial phase of trauma management at two level 1 trauma centers, TC1 and TC2. METHODS: In this prospective, observational study we included trauma patients ≥16 years of age. Data on pre- and in-hospital supplemental oxygen, arterial oxygen tension (PaO2 ), and outcomes (in-hospital mortality, hospital- and intensive care unit length of stay) were collected. RESULTS: We included 56 patients. There were 22 (39%) females with a mean age of 49 years (SD: 18) and a median Injury Severity Score of 9 (IQR: 4-14, n = 49). A total of 23 (45%) out of 51 spontaneously breathing patients received pre-hospital supplemental oxygen, but did not differ significantly from the patients that did not receive supplemental oxygen. In-hospital, 29 (59%) out of 49 spontaneously breathing patients received supplemental oxygen. The median PaO2 was 26.5 kPa [IQR: 22.2-34.1] in four intubated patients and 12.3 kPa [IQR: 9.7-25.7] in eight patients with spontaneous respiration on supplemental oxygen. At TC1 a significantly greater proportion of spontaneously breathing patients received both pre-hospital (TC1: 18 [64%]; TC2: 5 [21%], P = 0.002) and in-hospital (TC1: 24 [92%]; TC2: 7 [30%], P < 0.001) supplemental oxygen. CONCLUSION: Approximately 50% of trauma patients received supplemental oxygen during the initial treatment. Hyperoxemia was a common finding for patients treated with supplemental oxygen, and it was more pronounced in intubated patients.

Restrictive vs liberal oxygen for trauma patients-the TRAUMOX1 pilot randomised clinical trial.

INTRODUCTION: Hyperoxaemia is commonly observed in trauma patients but has been associated with pulmonary complications and mortality in some patient populations. The objectives of this study were to evaluate whether maintenance of normoxia is feasible using a restrictive oxygen strategy in the initial phase after trauma and to evaluate the incidence of 30-day mortality and/or major pulmonary complications. METHODS: Forty-one adult trauma patients admitted to our trauma centre were randomised to 24 hours of restrictive oxygen therapy (no supplemental oxygen if the arterial oxyhaemoglobin saturation (SpO2 ) was at least 94%, n = 21) or liberal oxygen therapy (intubated patients: FiO2 1.0 in the trauma bay, 0.8-1.0 elsewhere; spontaneously breathing patients: 15 L/min via a non-rebreather mask, n = 20). Two blinded anaesthesiologists evaluated major in-hospital pulmonary complications within 30 days. RESULTS: Protocol compliance was high, as the median arterial oxygen tension was significantly lower in the restrictive group (10.8 kPa [9.7-12.0] vs 30.4 kPa [23.7-39.0], P < 0.0001). There were seven episodes of SpO2 below 90% in the restrictive group and one episode in the liberal group. Thirty-day mortality and/or major in-hospital pulmonary complications occurred in 4/20 (20%) in the restrictive group and in 6/18 (33%) in the liberal group: two patients in each group died within 30 days and the incidence of major in-hospital pulmonary complications was 2/20 (10%) in the restrictive group and 4/18 (22%) in the liberal group. CONCLUSION: Maintenance of normoxia using a restrictive oxygen strategy following trauma is feasible. This pilot study serves as the basis for a larger clinical trial.

The Effects of Public Access Defibrillation on Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review of Observational Studies.

BACKGROUND: Despite recent advances, the average survival after out-of-hospital cardiac arrest (OHCA) remains <10%. Early defibrillation by an automated external defibrillator is the most important intervention for patients with OHCA, showing survival proportions >50%. Accordingly, placement of automated external defibrillators in the community as part of a public access defibrillation program (PAD) is recommended by international guidelines. However, different strategies have been proposed on how exactly to increase and make use of publicly available automated external defibrillators. This systematic review aimed to evaluate the effect of PAD and the different PAD strategies on survival after OHCA. METHODS: PubMed, Embase, and the Cochrane Library were systematically searched on August 31, 2015 for observational studies reporting survival to hospital discharge in OHCA patients where an automated external defibrillator had been used by nonemergency medical services. PAD was divided into 3 groups according to who applied the defibrillator: nondispatched lay first responders, professional first responders (firefighters/police) dispatched by the Emergency Medical Dispatch Center (EMDC), or lay first responders dispatched by the EMDC. RESULTS: A total of 41 studies were included; 18 reported PAD by nondispatched lay first responders, 20 reported PAD by EMDC-dispatched professional first responders (firefighters/police), and 3 reported both. We identified no qualified studies reporting survival after PAD by EMDC-dispatched lay first responders. The overall survival to hospital discharge after OHCA treated with PAD showed a median survival of 40.0% (range, 9.1-83.3). Defibrillation by nondispatched lay first responders was associated with the highest survival with a median survival of 53.0% (range, 26.0-72.0), whereas defibrillation by EMDC-dispatched professional first responders (firefighters/police) was associated with a median survival of 28.6% (range, 9.0-76.0). A meta-analysis of the different survival outcomes could not be performed because of the large heterogeneity of the included studies. CONCLUSIONS: This systematic review showed a median overall survival of 40% for patients with OHCA treated by PAD. Defibrillation by nondispatched lay first responders was found to correlate with the highest impact on survival in comparison with EMDC-dispatched professional first responders. PAD by EMDC-dispatched lay first responders could be a promising strategy, but evidence is lacking.

Comparison of a short versus long-course antibiotic therapy for ventilator-associated pneumonia: a systematic review and meta-analysis of randomized controlled trials.

Background: For ventilator-associated pneumonia (VAP), the safety of short-course versus long-course antibiotic therapy is still debated, especially regarding documented VAP due to non-fermenting Gram-negative bacilli (NF-GNB). The aim of this meta-analysis was to assess the rates of recurrence and relapse of VAP in patients receiving short-course (≤8 days) and long-course (≥10-15 days) of antibiotic therapy. Methods: The protocol for this study was registered in the PROSPERO database (ID: CRD42022365138). We performed an electronic search of the relevant literature and limited our search to data published from 2000 until September 1, 2022. We searched for randomized controlled trials (RCTs) in the United States National Library of Medicine, Cochrane Database of Systematic Reviews (CDSR) and the Cochrane Central Register of Controlled Trials (CENTRAL), Embase, National Institutes of Health PubMed/MEDLINE, web of science and Google Scholar databases. The primary endpoint was the recurrence and relapses of VAP, secondary endpoints were 28-day mortality, mechanical ventilation duration, number of extra-pulmonary infections and length of ICU stay. Findings: We identified five relevant studies involving 1069 patients (530 patients in the short-course group and 539 patients in the long-course group). The meta-analysis did not reveal any significant difference between short and long-course antibiotic therapy for recurrence and relapses of VAP (odd ratio "OR" = 1.48, 95% confidence intervals (CI) [0.96, 2.28], p = 0.08 and OR = 1.45, 95% CI [0.94, 2.22], p = 0.09, respectively), including those due to NF-GNB (OR = 1.90, 95% CI [0.93, 3.33], p = 0.05 and OR = 1.76, 95% CI [0.93, 3.33], p = 0.08, respectively). No difference was found for 28 days-mortality (OR = 1.24, 95% CI [0.92, 1.67], p = 0.16), mechanical ventilation duration, number of extra-pulmonary infections and length of ICU stay. However, short-course therapy significantly increased the number of antibiotic-free days. Interpretation: Our meta-analysis showed that short-course antibiotic therapy did not result in increased number of recurence and relapses of VAP, suggesting that short-course should be preferred to reduce the exposure to antibiotics. Funding: None.

A high fraction of inspired oxygen may increase mortality in intubated trauma patients - A retrospective cohort study.

BACKGROUND: Mechanical ventilation of trauma patients is common, and many will require a higher than normal fraction of inspired oxygen (FiO2) to avoid hypoxaemia. The primary objective of this study was to assess the association between FiO2 and all-cause, one-year mortality in intubated trauma patients. METHODS: Adult trauma patients intubated in the initial phase post-trauma between 2015 and 2017 were retrospectively identified. Information on FiO2 during the first 24 hours of hospitalisation and mortality was registered. For each patient the number of hours of the first 24 hours exposed to an FiO2 ≥ 80%, ≥ 60%, and ≥ 40%, respectively, were determined and categorised into exposure durations. The associations of these FiO2 exposures with mortality were evaluated using Cox regression adjusting for age, sex, body mass index (BMI), Injury Severity Score (ISS), prehospital Glasgow Coma Scale (GCS) score, and presence of thoracic injuries. RESULTS: We included 218 intubated trauma patients. The median prehospital GCS score was 6 and the median ISS was 25. One-year mortality was significantly increased when patients had received an FiO2 above 80% for 3-4 hours compared to <2 hours (hazard ratio (95% CI) 2.7 (1.3-6.0), p= 0.011). When an FiO2 above 80% had been administered for more than 4 hours, there was a trend towards a higher mortality as well, but this was not statistically significant. There was a significant, time-dependent increase in mortality for patients who had received an FiO2 ≥ 60%. There was no significant relationship observed between mortality and the duration of FiO2 ≥ 40%. CONCLUSION: A fraction of inspired oxygen above 60% for more than 2 hours during the first 24 hours of admission was associated with increased mortality in intubated trauma patients in a duration-dependent manner. However, given the limitations of this retrospective study, the findings need to be confirmed in a larger, randomized set-up.

Comparing restrictive versus liberal oxygen strategies for trauma patients - the TRAUMOX2 trial: protocol for a randomised clinical trial.

INTRODUCTION: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma. METHODS AND ANALYSIS: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO2 of 94%. The liberal group receives 12-15 L O2/min or FiO2=0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group. ETHICS AND DISSEMINATION: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBERS: EudraCT 2021-000556-19; NCT05146700.

Determining a safe upper limit of oxygen supplementation for adult patients: a systematic review.

OBJECTIVE: This systematic review aimed to describe the connection between the inspired oxygen fraction and pulmonary complications in adult patients, with the objective of determining a safe upper limit of oxygen supplementation. METHODS: MEDLINE and Embase were systematically searched in August 2019 (updated July 2020) for studies fulfilling the following criteria: intubated adult patients (Population); high fractions of oxygen (Intervention) versus low fractions of (Comparison); atelectasis, acute respiratory distress syndrome (ARDS), pneumonia and/or duration of mechanical ventilation (Outcome); original studies both observational and interventional (Studies). Screening, data extraction and risk of bias assessment was done by two independent reviewers. RESULTS: Out of 6120 records assessed for eligibility, 12 were included. Seven studies were conducted in the emergency setting, and five studies included patients undergoing elective surgery. Eight studies reported data on atelectasis, two on ARDS, four on pneumonia and two on duration of mechanical ventilation. There was a non-significant increased risk of atelectasis if an oxygen fraction of 0.8 or above was used, relative risk (RR): 1.37 (95% CI 0.95 to 1.96). One study showed an almost threefold higher risk of pneumonia in the high oxygen fraction group (RR: 2.83 (95% CI 2.25 to 3.56)). The two studies reporting ARDS and the two studies with data on mechanical ventilation showed no association with oxygen fraction. Four studies had a high risk of bias in one domain. CONCLUSIONS: In this systematic review, we found inadequate evidence to identify a safe upper dosage of oxygen, but the identified studies suggest a benefit of keeping inspiratory oxygen fraction below 0.8 with regard to formation of atelectases. PROSPERO REGISTRATION NUMBER: CRD42020154242.

Ketamine versus propofol for rapid sequence induction in trauma patients: a retrospective study.

BACKGROUND: Rapid Sequence Induction (RSI) is used for emergency tracheal intubation to minimise the risk of pulmonary aspiration of stomach contents. Ketamine and propofol are two commonly used induction agents for RSI in trauma patients. Yet, no consensus exists on the optimal induction agent for RSI in the trauma population. The aim of this study was to compare 30-day mortality in trauma patients after emergency intubation prehospitally or within 30 min after arrival in the trauma centre using either ketamine or propofol for RSI. METHODS: In this investigator-initiated, retrospective study we included adult trauma patients emergently intubated with ketamine or propofol registered in the local trauma registry at Rigshospitalet, a tertiary university hospital that hosts a level-1 trauma centre. The primary outcome was 30-day mortality. Secondary outcomes included hospital and Intensive Care Unit length of stay as well as duration of mechanical ventilation. We analysed outcomes using multivariable logistic regression models adjusting for age, sex, injury severity score, shock (systolic blood pressure < 90 mmHg) and Glasgow Coma Scale score before intubation and present results as odds ratios (ORs) with 95% confidence intervals. RESULTS: From January 1st, 2015 through December 31st, 2019 we identified a total of 548 eligible patients. A total of 228 and 320 patients received ketamine and propofol, respectively. The 30-day mortality for patients receiving ketamine and propofol was 20.2% and 22.8% (P = 0.46), respectively. Adjusted OR for 30-day mortality was 0.98 [0.58-1.66], P = 0.93. We found no significant association between type of induction agent and hospital length of stay, Intensive Care Unit length of stay or duration of mechanical ventilation. CONCLUSIONS: In this study, trauma patients intubated with ketamine did not have a lower 30-day mortality as compared with propofol.