Cocaine versus xylometazoline to prevent epistaxis after nasotracheal intubation: A randomized trial.

BACKGROUND: Nasotracheal intubation is associated with a risk of epistaxis. Several drugs, including cocaine and xylometazoline may be used as decongestants prior to nasotracheal intubation to prevent this. We hypothesized that xylometazoline would prevent epistaxis more effectively than cocaine, demonstrated by a lower proportion of patients with bleeding after nasotracheal intubation. METHODS: We conducted a single-center, outcome assessor and analyst-blinded, clinical randomized controlled trial following approval from the local research ethics committee and the national medicine agency. Written informed consent was obtained from all patients. Patients scheduled for surgery under general anesthesia with nasotracheal intubation were randomized to receive either 2 mL 4% cocaine or 2 mL 0.05% xylometazoline prior to nasotracheal intubation. Immediately following intubation, epistaxis was evaluated by the blinded intubating anesthetist on a four-point scale. We measured heart rate and blood pressure the first 5 min after drug administration. Adverse events were followed up after 24 h. RESULTS: A total of 53 patients received cocaine and 49 patients received xylometazoline. Bleeding occurred in 32 patients receiving cocaine (60.4%) and in 34 patients receiving xylometazoline (69.4%) (p = .41, Fisher's exact test) with a difference of 9.0% (95% CI: -9.4% to 27%). There was no statistically significant difference between groups regarding the heart rate or blood pressure. No adverse cardiac events were recorded in either group. CONCLUSION: We found no statistically significant difference between cocaine and xylometazoline in preventing epistaxis after nasotracheal intubation, and the choice of vasoconstrictor should be based on other considerations, such as pricing, availability and medicolegal issues.

Detection of cocaine 24 h after administration before nasotracheal intubation.

BACKGROUND: Cocaine may be applied to decongest the nasal mucosa before nasotracheal intubation, but patients risk a criminal offence if cocaine is detected when patients drive a car shortly after surgery. We aimed to evaluate whether benzoylecgonine levels in saliva exceeded the cut-off point 24 h after administration in patients undergoing nasotracheal intubation and whether cocaine would be detectable above the Danish legal fixed limit in blood samples 1 and 24 h after surgery. METHODS: We conducted a prospective study following approval from the local research ethics committee and the national medicine agency. Written informed consent was obtained from all patients. We included patients scheduled for surgery under general anaesthesia with nasotracheal intubation. They received 80 mg cocaine as a nasal spray 5 min before induction and nasotracheal intubation. The primary outcome was a dichotomous assessment of benzoylecgonine levels in saliva samples measured 24 h after administration of nasal cocaine with a cut-off limit of 200 ng/mL. Secondary outcomes were dichotomous assessments of cocaine in whole blood samples measured 1 and 24 h after administration of nasal cocaine with a cut-off limit of 0.01 mg/kg. RESULTS: Overall, 70 patients had valid saliva samples and 75 had valid blood samples 24 h after cocaine administration. Benzoylecgonine in saliva was traceable above the cut-off in 9/70 patients (13%; CI95%: 6% to 23%), and cocaine in blood was detected above the cut-off in 2/75 patients (3%; CI95%: 0.3% to 9%). CONCLUSION: We found benzoylecgonine traceable in saliva in 13% of patients and cocaine traceable in blood in 3% of patients 24 h after administration of 80 mg nasal cocaine. Patients should be informed when receiving cocaine and advised not to drive for at least 24 h.

Onset time, duration of action, and intubating conditions after mivacurium in elderly and younger patients.

BACKGROUND: The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults. METHODS: This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 µg kg-1 and propofol 1.5-2.5 mg kg-1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg-1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness. CONCLUSION: No difference in onset time of mivacurium 0.2 mg kg-1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions.

Prolonged duration of action of suxamethonium in pregnant and postpartum patients: A registry study.

BACKGROUND: Suxamethonium is hydrolysed by butyrylcholinesterase (BChE) and a low BChE activity can result in a prolonged duration of action of suxamethonium. The BChE activity is reduced during pregnancy and postpartum period by up to 33%. However, it can also be reduced by mutations in the BChE gene. In this study, we assessed BChE activity and mutations in the BChE gene in pregnant and postpartum patients with prolonged duration of action of suxamethonium. It was hypothesised that at least 30% of patients with a low BChE activity did not have a mutation in the BChE gene. METHODS: In this registry study we focused on pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium referred to the Danish Cholinesterase Research Unit (DCRU) between March 2007 and January 2023. Primary outcome was the proportion of patients without a mutation among patients with a low BChE activity. Secondary outcomes were the proportion of patients with a low BChE activity and the proportion of patients with a mutation out of the total number of patients. RESULTS: A total of 40 patients were included and among patients with a low BChE activity, 6% (95% CI: 1%-21%) did not have a mutation. Out of the total number of included patients referred to the DCRU, 90% (95% CI: 76%-97%) had a mutation and 94% (95% CI: 80%-99%) had a low BChE activity. CONCLUSION: Among pregnant and postpartum patients with a history of prolonged duration of action of suxamethonium and a low BChE activity, 6% did not have a mutation in the BChE gene. Our findings suggest that during pregnancy and postpartum clinically relevant prolonged duration of action of suxamethonium rarely occurs in genotypically normal patients.

Availability of social authorities in a simulated paediatric emergency.

INTRODUCTION: In cases of parental opposition to emergency medical care for minors, defined as children below 15 years of age, involving the social authorities may be necessary. When medical personnel assess that an intervention is in the minor's best interests, approval for such intervention is warranted from the local authorities in the municipality of residence. It was the primary aim of this study to assess the urgent availability of these authorities. METHODS: The urgent phone availability of social authorities at the 98 Danish local municipal offices was assessed during both regular hours and off-hours. The primary objective was to assess availability during regular hours. Urgent availability was predefined as obtained contact to a self-proclaimed accountable authority within 30 minutes. Secondary objectives were assessment of off-hour availability, time until obtained contact and number of contact links. RESULTS: Contact was obtained within 30 minutes in 59 inquiries (~ 58%) made during regular hours, with a median of three contact links and a median time until contact of eight minutes (interquartile range (IQR): 5.5-11 minutes). During off-hours, contact was obtained within 30 minutes in 91 inquiries (~ 93%), with a median of two contact links and a median time until contact of seven minutes (IQR: 5-12 minutes). CONCLUSION: During regular hours, we found that an accountable authority was urgently available for attendance to a case of parental opposition to emergency medical care of a minor within 30 minutes at the local municipal office in 58% of Danish municipalities. FUNDING: None. TRIAL REGISTRATION: Not relevant.

Association of Trauma With Long-Term Risk of Death and Immune-Mediated or Cancer Disease in Same-Sex Twins.

Importance: Immediate consequences of trauma include a rapid and immense activation of the immune system, whereas long-term outcomes include premature death, physical disability, and reduced workability. Objective: To investigate if moderate to severe trauma is associated with long-term increased risk of death or immune-mediated or cancer disease. Design, Setting, and Participants: This registry-based, matched, co-twin control cohort study linked the Danish Twin Registry and the Danish National Patient Registry to identify twin pairs in which 1 twin had been exposed to severe trauma and the other twin had not from 1994 to 2018. The co-twin control design allowed for matching on genetic and environmental factors shared within twin pairs. Exposure: Twin pairs were included if 1 twin had been exposed to moderate to severe trauma and the other twin had not (ie, co-twin). Only twin pairs where both twins were alive 6 months after the trauma event were included. Main Outcome and Measure: Twin pairs were followed up from 6 months after trauma until 1 twin experienced the primary composite outcome of death or 1 of 24 predefined immune-mediated or cancer diseases or end of follow-up. Cox proportional hazards regression was used for intrapair analyses of the association between trauma and the primary outcome. Results: A total of 3776 twin pairs were included, and 2290 (61%) were disease free prior to outcome analysis and were eligible for the analysis of the primary outcome. The median (IQR) age was 36.4 (25.7-50.2) years. The median (IQR) follow-up time was 8.6 (3.8-14.5) years. Overall, 1268 twin pairs (55%) reached the primary outcome; the twin exposed to trauma was first to experience the outcome in 724 pairs (32%), whereas the co-twin was first in 544 pairs (24%). The hazard ratio for reaching the composite outcome was 1.33 (95% CI, 1.19-1.49) for twins exposed to trauma. Analyses of death or immune-mediated or cancer disease as separate outcomes provided hazard ratios of 1.91 (95% CI, 1.68-2.18) and 1.28 (95% CI, 1.14-1.44), respectively. Conclusion and Relevance: In this study, twins exposed to moderate to severe trauma had significantly increased risk of death or immune-mediated or cancer disease several years after trauma compared with their co-twins.

Tracheal intubating conditions in elderly patients when train-of-four count is zero after rocuronium 0.6 or 0.9 mg/kg. A secondary analysis.

PURPOSE: The neuromuscular blocking agent rocuronium can be administered to facilitate tracheal intubation. We hypothesized that rocuronium 0.9 mg/kg provided a larger proportion of patients with vocal cords in abducted position compared to rocuronium 0.6 mg/kg at train-of-four (TOF) 0. METHODS: This secondary analysis was based on 52 elderly surgical patients of which 36 patients received rocuronium 0.6 mg/kg and 16 patients received rocuronium 0.9 mg/kg. Neuromuscular block was monitored with acceleromyography with TOF stimulation at the ulnar nerve. The primary outcome was the proportion of patients with vocal cords in abducted position at TOF 0. Secondary outcomes were intubating conditions evaluated by the Fuchs-Buder scale, the Intubating Difficulty Score (IDS), onset time, and duration of action of rocuronium. RESULTS: At TOF 0, a significantly larger proportion of patients had vocal cords in abducted position in the rocuronium 0.9 mg/kg group (81%) compared with the rocuronium 0.6 mg/kg group (53%); difference (%) 28, 95% Cl 3-53, P = 0.05. Excellent intubating conditions (Fuchs-Buder) were more common in the rocuronium 0.9 mg/kg group (62.5%); difference (%) 32.5, 95% Cl 4-61), P = 0.03. No significant difference was found in IDS or onset time of rocuronium (difference 19 s, 95% Cl: -5-43). Duration of action was significantly longer (difference 29 min, 95% Cl: 10-47) in the 0.9 mg/kg group. CONCLUSION: The proportion of patients with vocal cords in abducted position was significantly larger after rocuronium 0.9 mg/kg compared to rocuronium 0.6 mg/kg at TOF 0 monitored at the ulnar nerve.

Transcutaneous carbon dioxide monitoring during prolonged apnoea with high-flow nasal oxygen.

BACKGROUND: The duration of apnoeic oxygenation with high-flow nasal oxygen is limited by hypercapnia and acidosis and monitoring of arterial carbon dioxide level is therefore essential. We have performed a study in patients undergoing prolonged apnoeic oxygenation where we monitored the progressive hypercapnia with transcutaneous carbon dioxide. In this paper, we compared the transcutaneous carbon dioxide level with arterial carbon dioxide tension. METHODS: This is a secondary publication based on data from a study exploring the limits of apnoeic oxygenation. We compared transcutaneous carbon dioxide monitoring with arterial carbon dioxide tension using Bland-Altman analyses in anaesthetised and paralysed patients undergoing prolonged apnoeic oxygenation until a predefined limit of pH 7.15 or PCO2 of 12 kPa was reached. RESULTS: We included 35 patients with a median apnoea duration of 25 min. Mean pH was 7.14 and mean arterial carbon dioxide tension was 11.2 kPa at the termination of apnoeic oxygenation. Transcutaneous carbon dioxide monitoring initially slightly underestimated the arterial tension but at carbon dioxide levels above 10 kPa it overestimated the value. Bias ranged from -0.55 to 0.81 kPa with limits of agreement between -1.25 and 2.11 kPa. CONCLUSION: Transcutaneous carbon dioxide monitoring provided a clinically acceptable substitute for arterial blood gases but as hypercapnia developed to considerable levels, we observed overestimation at high carbon dioxide tensions in patients undergoing apnoeic oxygenation with high-flow nasal oxygen.

Intra-operative blood transfusion in elderly patients on antithrombotic therapy.

BACKGROUND: Many elderly patients are receiving antithrombotics, which may increase intra-operative blood loss. We aimed to assess whether chronic antithrombotic therapy was associated with intra-operative transfusion of packed red blood cells in patients at least 80 years of age undergoing elective procedures. METHODS: We performed a secondary analysis of the prospective, observational European multicentre study entitled POSE (peri-interventional outcome study in the elderly) including 9497 surgical patients aged 80 years and older in 177 centres from October 2017 to December 2018. In this secondary analysis we included POSE patients who underwent elective procedures and with available data on chronic antithrombotic therapy. The primary outcome was intra-operative transfusion of packed red blood cells and results were analysed using multiple logistic regression model. We adjusted for the following predetermined explanatory variables: Age, sex, body mass index, American Society of Anaesthesiologists Physical Status Classification System, baseline haemoglobin concentration, disseminated cancer, and type and severity of surgery. RESULTS: A total of 7174 patients were included of whom 4073 (56.8%) were on antithrombotic therapy. Among patients on antithrombotic therapy 191 (4.7%) received intra-operative blood transfusion compared with 98 (3.2%) of patients not on chronic antithrombotic therapy (crude odds ratio: 1.51, 95% CI 1.18-1.94). Following multiple logistic regression analysis, the adjusted odds ratio was 0.98; 0.73-1.32. We found that chronic antithrombotic therapy was associated with intra-operative transfusion of packed red blood cells in elderly patients undergoing elective procedures in an unadjusted analysis, but not in a multivariate adjusted model.

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.

Rocuronium 0.3 or 0.9 mg/kg comparing onset time, duration of action, and intubating conditions in patients 80 years and older: A randomized study.

BACKGROUND: Limited data exist about the optimal dose of rocuronium for intubation in elderly patients. We hypothesized that rocuronium 0.9 mg/kg would lead to a shorter onset time than 0.3 mg/kg in patients above 80 years. METHODS: Thirty-four patients were randomized to either rocuronium 0.3 or 0.9 mg/kg. The primary outcome was onset time defined as time to train-of-four (TOF) count of 0. Other outcomes included duration of action (time to TOF ratio >0.9), proportion of excellent intubating conditions using the Fuchs-Buder scale and tracheal intubating conditions using the Intubating Difficulty Scale (IDS). RESULTS: Rocuronium 0.9 mg/kg resulted in shorter onset time compared to rocuronium 0.3 mg/kg; 108 s (SD 40) vs. 228 s (SD 140) (difference: 119 s [95% CI: 41-196], p = .005), respectively. However, in 66% of the patients receiving rocuronium 0.3 mg/kg a TOF count of 0 was not obtained. Duration of action was longer after rocuronium 0.9 mg/kg: 118 min (SD 43) vs. 46 min (SD 13) (difference: 72 min [95% CI: 49-95] p < .0001), and a greater proportion of excellent intubating conditions (Fuchs-Buder) was obtained; 11/16 (69%) vs 4/18 (22%) (p = .006). No difference was found regarding IDS score. CONCLUSION: Rocuronium 0.9 mg/kg resulted in a shorter onset time compared to rocuronium 0.3 mg/kg in patients above 80 years of age. In 66% of the patients receiving rocuronium 0.3 mg/kg a TOF count of 0 was not obtained.

Shock index as a predictor for mortality in trauma patients: a systematic review and meta-analysis.

PURPOSE: The primary aim was to determine whether a shock index (SI) ≥ 1 in adult trauma patients was associated with increased in-hospital mortality compared to an SI < 1. METHODS: This systematic review including a meta-analysis was performed in accordance with the PRISMA guidelines. EMBASE, MEDLINE, and Cochrane Library were searched, and two authors independently screened articles, performed the data extraction, and assessed risk of bias. Studies were included if they reported in-hospital, 30-day, or 48-h mortality, length of stay, massive blood transfusion or ICU admission in trauma patients with SI recorded at arrival in the emergency department or trauma center. Risk of bias was assessed using the Newcastle-Ottawa Scale, and the strength and quality of the body of evidence according to GRADE. Data were pooled using a random effects model. Inter-rater reliability was assessed with Cohen's kappa. RESULTS: We screened 1350 citations with an inter-rater reliability of 0.90. Thirty-eight cohort studies were included of which 14 reported the primary outcome. All studies reported a significant higher in-hospital mortality in adult trauma patients with an SI ≥ 1 compared to those having an SI < 1. Twelve studies involving a total of 348,687 participants were included in the meta-analysis. The pooled risk ratio (RR) of in-hospital mortality was 4.15 (95% CI 2.96-5.83). The overall quality of evidence was low. CONCLUSIONS: This systematic review found a fourfold increased risk of in-hospital mortality in adult trauma patients with an initial SI ≥ 1 in the emergency department or trauma center.

Agreement Between Standard and ICD-10-Based Injury Severity Scores.

INTRODUCTION: Injury Severity Score (ISS) is used to describe anatomical lesions. ISS is traditionally determined through medical record review (standard ISS), which requires specific training and may be time-consuming. An alternative way to obtain ISS is by use of ICD-9/10 injury diagnoses, and several conversion tools exist. We sought to evaluate the agreement between standard ISS and ISS obtained with two tools converting ICD-10 diagnoses. METHODS: Our cohort consisted of trauma patients ≥18 years admitted to Rigshospitalet between 1999 and 2016. The included patients had standard ISS recorded in the Trauma Audit and Research Network (TARN) database (ISS-TARN), and ICD-10 injury diagnoses for the trauma contact were recorded in the Danish National Patient Registry. We used the tools ICDPIC-R and ICD-AIS map to calculate ISS based on ICD-10 diagnoses. ICDPIC-R provided two ISSs: ISS-TQIP and ISS-NIS. The ICD-AIS map resulted in one ISS: ISS-map. The ISS-TARN was compared to the conversion tool ISSs using Bland-Altman plots. The agreement between ISS-TARN and the conversion tool ISSs for ISS above 15 was assessed using kappa statistics (κ). RESULTS: We included 4308 trauma patients. The median age was 44 years, 70% were male, and 92% had a blunt injury mechanism. The median ISS-TARN was 16 [IQR: 9-25], and the median conversion tool ISSs were 10 [2-25] (ISS-TQIP), 17 [5-26] (ISS-NIS), and 9 [4-16] (ISS-map). The Bland-Altman plots all showed increasing difference in ISS with increasing mean ISS. Bias ranged from -7.3 to 1.1 and limits of agreement ranged between -28.0 and 25.7. The agreement for ISS above 15 was fair to moderate (κ = 0.43 (ISS-TQIP), 0.44 (ISS-NIS), and 0.29 (ISS-map)). CONCLUSION: Using ICDPIC-R or ICD-AIS map to determine ISS is feasible, but limits of agreement were unacceptably wide. The agreement between ISS-TARN and ICDPIC-R was moderate for ISS above 15.

Hyperoxia and Antioxidants for Myocardial Injury in Noncardiac Surgery: A 2 × 2 Factorial, Blinded, Randomized Clinical Trial.

BACKGROUND: Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo. METHODS: A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days. RESULTS: The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and intraoperative characteristics did not differ between groups. The primary outcome was 35 ng · day/l (19 to 58) in the 80% oxygen group; 35 ng · day/l (17 to 56) in the 30% oxygen group; 35 ng · day/l (19 to 54) in the antioxidants group; and 33 ng · day/l (18 to 57) in the placebo group. The median difference between oxygen groups was 1.5 ng · day/l (95% CI, -2.5 to 5.3; P = 0.202) and -0.5 ng · day/l (95% CI, -4.5 to 3.0; P = 0.228) between antioxidant groups. Mortality at 30 days occurred in 9 of 576 patients (1.6%; odds ratio, 2.01 [95% CI, 0.50 to 8.1]; P = 0.329 for the 80% vs. 30% oxygen groups; and odds ratio, 0.79 [95% CI, 0.214 to 2.99]; P = 0.732 for the antioxidants vs. placebo groups). CONCLUSIONS: Perioperative interventions with high inspiratory oxygen fraction and antioxidants did not change the degree of myocardial injury within the first 3 days of surgery. This implies safety with 80% oxygen and no cardiovascular benefits of vitamin C and N-acetylcysteine in major noncardiac surgery.

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.

Biomarkers of Cerebral Injury for Prediction of Postoperative Cognitive Dysfunction in Patients Undergoing Cardiac Surgery.

OBJECTIVES: To assess the ability of the biomarkers neuron-specific enolase (NSE), tau, neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP) to predict postoperative cognitive dysfunction (POCD) at discharge in patients who underwent cardiac surgery. DESIGN: Post hoc analyses (with tests being prespecified before data analyses) from a randomized clinical trial. SETTING: Single-center study from a primary heart center in Denmark. PARTICIPANTS: Adult patients undergoing elective or subacute on-pump coronary artery bypass grafting and/or aortic valve replacement. INTERVENTIONS: Blood was collected before induction of anesthesia, after 24 hours, after 48 hours, and at discharge from the surgical ward. The International Study of Postoperative Cognitive Dysfunction test battery was applied to diagnose POCD at discharge and after three months. Linear mixed models of covariance were used to assess whether repeated measurements of biomarker levels were associated with POCD. Receiver operating characteristic (ROC) curves were applied to assess the predictive value of each biomarker measurement for POCD. MEASUREMENTS AND MAIN RESULTS: A total of 168 patients had biomarkers measured at baseline, and 47 (28%) fulfilled the POCD criteria at discharge. Patients with POCD at discharge had significantly higher levels of tau (p = 0.02) and GFAP (p = 0.01) from baseline to discharge. The biomarker measurements achieving the highest area under the ROC curve for prediction of POCD at discharge were NFL measured at discharge (AUC, 0.64; 95% confidence interval [CI], 0.54-0.73), GFAP measured 48 hours after induction (AUC, 0.64; 95% CI, 0.55-0.73), and GFAP measured at discharge (AUC, 0.64; 95% CI, 0.54-0.74), corresponding to a moderate predictive ability. CONCLUSIONS: Postoperative serum levels of tau and GFAP were significantly elevated in cardiac surgery patients with POCD at discharge, however, the biomarkers achieved only modest predictive abilities for POCD at discharge. Postoperative levels of NSE were not associated with POCD at discharge.

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.

Neurosurgical Admission Later Than 4 h After the Emergency Call Does Not Result in Worse Long-Term Outcome in Subarachnoid Haemorrhage.

Background: Few studies have investigated the importance of the time interval between contact to the emergency medical service and neurosurgical admission in patients with spontaneous subarachnoid haemorrhage. We hypothesised that longer time to treatment would be associated with an increased risk of death or early retirement. Methods: This was a retrospective observational study with 4 years follow-up. Those who reached a neurosurgical department in fewer than 4 h were compared with those who reached it in more than 4 h. Individual level data were merged from the Danish National Patient Register, medical records, the Copenhagen Emergency Medical Dispatch Centre, the Civil Registration System, and the Ministry of Employment and Statistics Denmark. Patients were ≥18 years and had a verified diagnosis of spontaneous subarachnoid haemorrhage. The primary outcome was death or early retirement after 4 years. Results: Two hundred sixty-two patients admitted within a three-and-a-half-year time period were identified. Data were available in 124 patients, and 61 of them were in their working age. Four-year all-cause mortality was 25.8%. No significant association was found between time to neurosurgical admission and risk of death or early retirement (OR = 0.35, 95% confidence interval [CI]: 0.10-1.23, p = 0.10). Conclusion: We did not find an association between the time from emergency telephone call to neurosurgical admission and the risk of death or early retirement.

The Role of a Physician-Staffed Helicopter in Emergency Care of Patients on Isolated Danish Islands.

Emergency calls may lead to the dispatch of either ground ambulances or helicopter emergency medical services (HEMS). For residents on isolated islands, the HEMS can reduce the time to hospital admission and lead to improved outcomes. This study investigated the emergency care for residents on isolated islands with a focus on the role of a physician-staffed helicopter. The data were obtained from Danish national registries and databases. We included data on emergency calls from isolated islands from the time of emergency call to discharge. We identified 1130 emergency calls from which 775 patients were registered with a hospital admission. Of these, 41% were transported by the HEMS and 36% by a ground ambulance. The median time to admission was 83 min (IQR 66-104) and 90 min (IQR 45-144) for the HEMS and ground ambulance, respectively (p = 0.26). The overall 30-day mortality was 6.2% (95% CI: 4.6-8.1%), and 37% of all the patients were admitted to the hospital with an unspecified diagnosis. The emergency calls from isolated islands led to the dispatch of the HEMS in 41% of the cases. The use of the HEMS did not significantly reduce the time to admission but was used in a greater proportion of patients with an acute cardiac disease (66%) or stroke (67%).

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.