Intravenous MELAtonin for prevention of Postoperative Agitation and Emergence Delirium in children (MELA-PAED): A protocol and statistical analysis plan for a randomized clinical trial.

BACKGROUND: Emergence agitation and delirium in children remain a common clinical challenge in the post-anesthetic care unit. Preoperative oral melatonin has been suggested as an effective preventive drug with a favorable safety profile. The oral bioavailability of melatonin, however, is low. Therefore, the MELA-PAED trial aims to investigate the efficacy and safety of intraoperative intravenous melatonin for the prevention of emergence agitation in pediatric surgical patients. METHODS: MELA-PAED is a randomized, double-blind, parallel two-arm, multi-center, superiority trial comparing intravenous melatonin with placebo. Four hundred participants aged 1-6 years will be randomized 1:1 to either the intervention or placebo. The intervention consists of intravenous melatonin 0.15 mg/kg administered approximately 30 min before the end of surgery. Participants will be monitored in the post-anesthetic care unit (PACU), and the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) will be performed on days 1, 7, and 14 after the intervention. Serious Adverse Events (SAE) will be assessed up to 30 days after the intervention. RESULTS: The primary outcome is the incidence of emergence agitation, assessed dichotomously as any Watcha score >2 during the participant's stay in the post-anesthetic care unit. Secondary outcomes are opioid consumption in the post-anesthetic care unit and adverse events. Exploratory outcomes include SAEs, postoperative pain, postoperative nausea and vomiting, and time to awakening, to first oral intake, and to discharge readiness. CONCLUSION: The MELA-PAED trial investigates the efficacy of intravenous intraoperative melatonin for the prevention of emergence agitation in pediatric surgical patients. Results may provide further knowledge concerning the use of melatonin in pediatric perioperative care.

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).

Comparison of onset time, duration of action, and intubating conditions after cisatracurium 0.15 mg/kg in young and elderly patients.

INTRODUCTION: Tracheal intubation during anesthesia can be facilitated by the neuromuscular blocking agent cisatracurium. However, limited data exists about onset time, duration of action and effect on intubating conditions in elderly patients above 80 years of age. We hypothesized that elderly patients would present a longer onset time and duration of action compared to younger adults. METHODS: This prospective observational study included 31 young (18-40 years) and 29 elderly (≥ 80 years) patients. Patients were given fentanyl 2 µg/kg and propofol 1.5-2.5 mg/kg for induction of anesthesia and maintained with remifentanil and propofol. Monitoring of neuromuscular function was performed with acceleromyography. Primary outcome was onset time defined as time from injection of cisatracurium 0.15 mg/kg (based on ideal body weight) to a train-of-four (TOF) count of 0. Other outcomes included duration of action (time to TOF ratio ≥ 0.9), intubation conditions using the Fuchs-Buder scale and the Intubating Difficulty Scale (IDS), and occurrence of hoarseness and sore throat postoperatively. RESULTS: Elderly patients had significantly longer onset time compared with younger patients; 297 seconds (SD 120) vs. 199 seconds (SD 59) (difference: 98 seconds (95% CI: 49-147), P < 0.001)). Duration of action was also significantly longer in elderly patients compared with younger patients; 89 minutes (SD 17) vs. 77 minutes (SD 14) (difference: 12 minutes (95% CI: 2.5-20.5) P = 0.01)). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 19/29 (66%) vs 21/31 (68%) (P = 0.86) or IDS score (P = 0.74). A larger proportion of elderly patients reported hoarseness 24 hours postoperatively; 62% vs 34% P = 0.04. CONCLUSION: In elderly patients cisatracurium 0.15 mg/kg had significantly longer onset time and duration of action compared with younger patients. No difference was found in intubating conditions at a TOF count of 0. TRIAL REGISTRATION: Clinicaltrials.gov (NCT04921735, date of registration 10 June 2021).

Spontaneous Subarachnoid Haemorrhage as a Cause of Out-of-Hospital Death.

BACKGROUND: There are no recent studies on the incidence rate of out-of-hospital death due to spontaneous subarachnoid haemorrhage (SAH). The primary aim of this study was to determine how often SAH was the cause of out-of-hospital death. The secondary aim was to determine if decedents had contacted any health care services within the last 72 h prior to the time of death. METHODS: This was a retrospective cohort study. The reports of all autopsies carried out at the Department of Forensic Medicine in the Capital Region of Denmark in a ten-year period were read. Police records and Emergency Medical Services (EMS) telephone records were searched for health care contacts within the last 72 h prior to the time of death. Descriptive statistics were used, and to analyse the incidence rates for trend Poisson regression was used. RESULTS: In total, 6,903 decedents underwent autopsy. Out-of-hospital SAH was the cause of death in 58 decedents, resulting in an average incidence rate of 0.34 per 100.000 persons per year. No significant change in the incidence rate over time was found (p = 0.52). No EMS data were available for eleven decedents in the first part of the study period. Of the remaining 47 decedents, 2 (3.5%, 95% CI: 0.4-11.9) had called the EMS, and in regards to 27 of the 58 decedents, the police records contained information on health care system contacts. Five (8.6%, 95% CI: 2.9-18.9) patients had contacted a general practitioner and three (5.2%, 95% CI: 1.1-14.4) patients had been admitted to hospital but were discharged again within 72 h prior to their death. CONCLUSION: The incidence rate of out-of-hospital death from SAH was 0.34 per 100.000 persons per year and remained stable across the years 2009-2018. Several patients had sought medical attention shortly before their death, emphasizing the vital importance of recognizing the early symptoms of SAH.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as an Added Predictor to Existing Preoperative Risk Assessments.

BACKGROUND: Risk assessment strategies, such as using the American Society of Anesthesiologists (ASA) physical status classification, attempt to identify surgical high-risk patients. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker reflecting overall systemic inflammation and immune activation, and it could potentially improve the identification of high-risk surgical patients. METHODS: We included patients acutely admitted to the emergency department who subsequently underwent surgery within 90 days of admission. Patients were stratified into low-risk or high-risk groups, according to ASA classification (ASAlow: ASA I-II; ASAhigh: ASA III-VI) and suPAR level, measured at admission (suPARhigh above and suPARlow below 5.5 ng/ml), respectively. Pre-specified complications were identified in national registries and electronic medical records. The association between ASA classification, suPAR level, CRP and the rate of postoperative complications was analyzed with logistic regression and Cox regression analyses, estimating odds ratios and hazard ratios (HRs). RESULTS: During 90-day follow-up from surgery, 31 (7.0%) patients died and 158 (35.6%) patients had postoperative complications. After adjusting for age, sex, and ASA classification, the HR for 90-day postoperative mortality was 2.5 (95% CI 1.6-4.0) for every doubling of suPAR level. suPAR was significantly better than CRP at predicting mortality and all complications (P = 0.0036 and P = 0.0041, respectively). Combining ASA classification and suPAR level significantly improved prediction of mortality and the occurrence of a postoperative complication within 90 days after surgery (P < 0.0001). CONCLUSION: Measuring suPAR levels in acutely admitted patients may aid in identifying high-risk patients and improve prediction of postoperative complications.

Risk assessment models for potential use in the emergency department have lower predictive ability in older patients compared to the middle-aged for short-term mortality - a retrospective cohort study.

BACKGROUND: Older patients is a complex group at increased risk of adverse outcomes compared to younger patients, which should be considered in the risk assessment performed in emergency departments. We evaluated whether the predictive ability of different risk assessment models for acutely admitted patients is affected by age. METHODS: Cohort study of middle-aged and older patients. We investigated the accuracy in discriminating between survivors and non-survivors within 7 days of different risk assessment models; a traditional triage algorithm, a triage algorithm with clinical assessment, vital signs, routine biomarkers, and the prognostic biomarker soluble urokinase plasminogen activator receptor (suPAR). RESULTS: The cohort included 22,653 (53.2%) middle-aged patients (age 40-69 years), and 19,889 (46.8%) older patients (aged 70+ years). Death within 7 days occurred in 139 patients (0.6%) in middle-aged patients and 596 (3.0%) of the older patients. The models based on vital signs and routine biomarkers had the highest area under the curve (AUC), and both were significantly better at discriminating 7-day mortality in middle-aged patients compared to older patients; AUC (95% CI): 0.88 (0.84-0.91), 0.75 (0.72-0.78), P < 0.01, and 0.86 (0.82-0.90), 0.76 (0.73-0.78), P < 0.001. In a subgroup of the total cohort (6.400 patients, 15.0%), the suPAR level was available. suPAR had the highest AUC of all individual predictors with no significant difference between the age groups, but further research in this biomarker is required before it can be used. CONCLUSION: The predictive value was lower in older patients compared to middle-aged patients for all investigated models. Vital signs or routine biomarkers constituted the best models for predicting 7-day mortality and were better than the traditional triage model. Hence, the current risk assessment for short-term mortality can be strengthened, but modifications for age should be considered when constructing new risk assessment models in the emergency department.

A simple clinical assessment is superior to systematic triage in prediction of mortality in the emergency department.

OBJECTIVE: To compare the Danish Emergency Process Triage (DEPT) with a quick clinical assessment (Eyeball triage) as predictors of short-term mortality in patients in the emergency department (ED). METHODS: The investigation was designed as a prospective cohort study conducted at North Zealand University Hospital. All patient visits to the ED from September 2013 to December 2013 except minor injuries were included. DEPT was performed by nurses. Eyeball triage was a quick non-systematic clinical assessment based on patient appearance performed by phlebotomists. Both triage methods categorised patients as green (not urgent), yellow, orange or red (most urgent). Primary analysis assessed the association between triage level and 30-day mortality for each triage method. Secondary analyses investigated the relation between triage level and 48-hour mortality as well as the agreement between DEPT and Eyeball triage. RESULTS: A total of 6383 patient visits were included. DEPT was performed for 6290 (98.5%) and Eyeball triage for 6382 (~100%) of the patient visits. Only patients with both triage assessments were included. The hazard ratio (HR) for 48-hour mortality for patients categorised as yellow was 0.9 (95% CI 0.4 to 1.9) for DEPT compared with 4.2 (95% CI 1.2 to 14.6) for Eyeball triage (green is reference). For orange the HR for DEPT was 2.2 (95% CI 1.1 to 4.4) and 17.1 (95% CI 5.1 to 57.1) for Eyeball triage. For red the HR was 30.9 (95% CI 12.3 to 77.4) for DEPT and 128.7 (95% CI 37.9 to 436.8) for Eyeball triage. For 30-day mortality the HR for patients categorised as yellow was 1.7 (95% CI 1.2 to 2.4) for DEPT and 2.4 (95% CI 1.6 to 3.5) for Eyeball triage. For orange the HR was 2.6 (95% CI 1.8 to 3.6) for DEPT and 7.6 (95% CI 5.1 to 11.2) for Eyeball triage, and for red the HR was 19.1 (95% CI 10.4 to 35.2) for DEPT and 27.1 (95% CI 16.9 to 43.5) for Eyeball triage. Agreement between the two systems was poor (kappa 0.05). CONCLUSION: Agreement between formalised triage and clinical assessment is poor. A simple clinical assessment by phlebotomists is superior to a formalised triage system to predict short-term mortality in ED patients.

Short-stay unit hospitalisation vs. standard care outcomes in older internal medicine patients-a randomised clinical trial.

Background: the effect of hospitalisation in emergency department-based short-stay units (SSUs) has not been studied in older patients. We compared SSU hospitalisation with standard care at an Internal Medicine Department (IMD) in acutely admitted older internal medicine patients. Methods: pragmatic randomised clinical trial. We randomly assigned patients aged 75 years or older, acutely admitted for an internal medicine disease and assessed to be suitable for SSU hospitalisation to SSU hospitalisation or IMD hospitalisation. SSU hospitalisation was provided by a pragmatic 'fast-track' principle. The primary outcome was 90-day mortality. Secondary outcomes included adverse events, change in Lawton Instrumental Activities of Daily Living (IADL) score within 90 days from admission, in-hospital length of stay and unplanned readmissions within 30 days after discharge. Results: between January 2015 and October 2016, 430 participants were randomised (median age 84 years in both groups). Ninety-day mortality was 22(11%) in the SSU group and 32(15%) in the IMD group (odds ratio (OR) 0.66; 95% confidence interval (CI) 0.37-1.18; P = 0.16). When comparing the SSU group to the IMD group, 16(8%) vs. 45(21%) experienced at least one adverse event (OR 0.31; 95% CI 0.17-0.56; P < 0.001); 6(3%) vs. 35(20%) experienced a reduction in IADL score within 90 days from admission (P < 0.001); median in-hospital length of stay was 73 h [interquartile range, IQR 36-147] vs. 100 h [IQR 47-169], (P < 0.001), and 26(13%) vs. 58(29%) were readmitted (OR 0.37; 95% CI 0.22-0.61; P < 0.001). Conclusions: mortality at 90 days after admission was not significantly lower in the SSU group, but SSU hospitalisation was associated with a lower risk of adverse events, less functional decline, fewer readmissions and shorter hospital stay. Trial registration: NCT02395718.

A critical assessment of early warning score records in 168,000 patients.

The national early warning score (NEWS) is recommended to detect deterioration in hospitalised patients. In 2013, a NEWS-based system was introduced in a hospital service with over 250,000 annual admissions, generating large amounts of NEWS data. The quality of such data has not been described. We critically assessed NEWS data recorded over 12 months. This observational study included NEWS records from adult inpatients hospitalized in the Capital Region of Denmark during 2014. Physiological variables and the use of supplementary oxygen (NEWS variables) were recorded. We identified implausible records and assessed the distributions of NEWS variable values. Of 2,835,331 NEWS records, 271,103 (10%) were incomplete with one or more variable missing and 0.2% of records containing implausible values. Digit preferences were identified for respiratory rate, supplementation oxygen flow, pulse rate, and systolic blood pressure. There was an accumulation of pulse rate records below 91 beats per minute. Among complete NEWS records, 64% had NEWS ≥ 1; 29% had NEWS ≥ 3; and 8% had NEWS ≥ 6. In a large set of NEWS data, 10% of the records were incomplete. In a system where data were manually entered into an electronic medical record, digit preferences and the accumulation of pulse rate records below 91 beats per minute, which is the limit for NEWS point generation, showed that staff practice influenced the recorded values. This indicates a potential limitation of transferability of research results obtained in such systems to fully automated systems.

The Impact of Intraoperative Fluid Therapy and Body Temperature on Surgical Site Infection - Re-Assessment of a Randomized Trial.

Background: Use of supplemental oxygen during surgery to reduce the incidence of SSI was investigated in the PROXI trial, which found no reduced frequency of SSI. Subsequently, it has been suggested that a restrictive fluid regimen and hypothermia in some patients could explain why no beneficial effect of supplemental oxygen was found. We evaluated the association between the occurrence of SSI and two perioperative factors, volume of infused fluid and body temperature (BT). Methods: We used data from the PROXI trial including 1,386 patients undergoing laparotomy randomly assigned to receive 80% or 30% oxygen during surgery. A fluid infusion index (FII) was calculated for each patient as the volume of infused fluids/body weight/duration of surgery. Results: SSI occurred in 18.9% of the patients in the lower FII tertile group (OR=0.86; P=0.41), in 20.4% in the upper FII tertile group (OR=1.49; P=0.05), in 19.7% of the patients with hypothermia (OR=1.28; P=0.25) and in 25.0% with hyperthermia (OR=1.26; P=0.52). An increased risk of SSI (OR=3.15; P=0.01) was found in patients having both hypothermia and emergency surgery. CONCLUSION: A trend towards an increased risk of SSI was seen in patients who received a greater volume of intravenous fluid. No association was found between BT and SSI.

Pentraxin-3 as a marker of disease severity and risk of death in patients with necrotizing soft tissue infections: a nationwide, prospective, observational study.

BACKGROUND: New biomarkers are needed to assess the severity of necrotizing soft tissue infection (NSTI) at an early stage and to individualize treatment strategies. We assessed pentraxin-3 (PTX3) as a marker of disease severity and risk of death in patients with NSTI. METHODS: We conducted a prospective, observational study in the intensive care unit at Copenhagen University Hospital, where treatment of NSTI is centralized at a national level. We compared PTX3, procalcitonin and C-reactive protein in septic shock versus nonshock patients and in amputated versus nonamputated patients using the Mann-Whitney U test. The prognostic value of the markers for 180-day mortality was assessed using Cox regression analyses. RESULTS: Patients with NSTI (n = 135) were included over 25 months with up to 2.5-year follow-up; 71% had septic shock, amputation was undertaken in 20% and the 180-day mortality was 27%. Baseline plasma PTX3 level was significantly higher in patients with septic shock (67.3 versus 24.6 ng/mL, p < 0.0001) and in patients who underwent amputation (118.6 versus 43.6 ng/mL, p = 0.019). No significant differences in baseline procalcitonin or C-reactive protein levels were found according to amputation (25.2 versus 7.0 µg/L, p = 0.060 and 202 versus 225 mg/L, p = 0.123), respectively. Baseline PTX3 level above the median was associated with death (p = 0.009, log-rank test) and the univariate Cox regression analysis revealed a significant association between PTX3 level upon admission and 180-day mortality (hazard ratio 2.60 (95% confidence interval 1.28-5.29), p = 0.008). When adjusted for age, sex, chronic disease and Simplified Acute Physiology Score II, no significant association was found. CONCLUSIONS: High PTX3 level is associated with septic shock, amputation and risk of death in patients with NSTI, but it is not an independent predictor of 180-day mortality in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02180906. Date of registration: June 29, 2014.

Cognitive dysfunction after fast-track hip and knee replacement.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is reported to occur after major surgery in as many as 20% of patients, elderly patients may especially experience problems in the weeks and months after surgery. Recent studies vary greatly in methods of evaluation and diagnosis of POCD, and the pathogenic mechanisms are still unclear. We evaluated a large uniform cohort of elderly patients in a standardized approach, after major joint replacement surgery (total hip and knee replacement). Patients were in an optimized perioperative approach (fast track) with multimodal opioid-sparing analgesia, early mobilization, and short length of stay (LOS ≤3 days) and discharged to home. METHODS: In a prospective multicenter study, we included 225 patients aged ≥60 years undergoing well-defined fast-track total hip or total knee replacement. Patients had neuropsychological testing preoperatively and 1 to 2 weeks and 3 months postoperatively. LOS, pain, opioid use, inflammatory response, and sleep quality were recorded. The practice effect of repeated cognitive testing was gauged using data from a healthy community-dwelling control group (n = 161). RESULTS: Median LOS was 2 days (interquartile range 2-3). The incidence of POCD at 1 to 2 weeks was 9.1% (95% confidence interval [CI], 5.4%-13.1%) and 8.0% (95% CI, 4.5%-12.0%) at 3 months. There was no statistically significant difference between patients with and without early POCD, regarding pain, opioid use, sleep quality, or C-reactive protein response, although the CIs were wide. Patients with early POCD had a higher Mini Mental State Examination score preoperatively (difference in medians 0.5 [95% CI, -1.0% to 0.0%]; P = 0.034). If there was an association between early POCD and late POCD, the sample size was unfortunately too small to verify this (23.6% of patients with early POCD had late onset vs 6.7% in non-POCD group; risk difference 16.9 (95% CI, -2.1% to 41.1%; P = 0.089). CONCLUSIONS: The incidence of POCD early after total hip and knee replacement seems to be lower after a fast-track approach than rates previously reported for these procedures, but late POCD occurred with an incidence similar to that in previous studies of major noncardiac elective surgery. No association between early and late POCD could be verified.

Shortened time to neuromuscular recovery with lower doses of rocuronium in elderly patients.

INTRODUCTION: The effect of neuromuscular blocking agents may be reversed by administration of neostigmine, when two twitches are present using train-of-four (TOF) stimulation. However, in elderly patients, limited data are available about when to administer neostigmine. We hypothesised that time to two twitches after TOF (TOF-2) was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg. Also, we hypothesised that time to TOF-2 would be shorter after rocuronium 0.3 mg/kg than after rocuronium 0.6 mg/kg. METHODS: This was a secondary analysis of 50 elderly patients > 80 years; 16 patients received rocuronium 0.6 mg/kg, another 16 patients received rocuronium 0.9 mg/kg; and, finally, 18 patients received rocuronium 0.3 mg/kg. Patients received total intravenous anaesthesia, and neuromuscular block was monitored with acceleromyography. RESULTS: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg: 37 min. versus 59 min. (difference: 22 min. (95% confidence intervals (CI): 10 to 33 min.), p = 0.0007). Time to TOF-2 after rocuronium 0.3 mg/kg was shorter than after rocuronium 0.6 mg/kg: 19 min. versus 37 min. (difference: 18 min. (95% CI: 11 to 25 min.), p = 0.00006). However, only 33% of the patients receiving 0.3 mg/kg obtained full effect i.e. TOF-0. CONCLUSION: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after 0.9 mg/kg and shorter after rocuronium 0.3 mg/kg than after 0.6 mg/kg. FUNDING: This work was supported by departmental sources. TRIAL REGISTRATION: This study was a secondary analysis of two clinical trials. CLINICALTRIALS: gov (NCT04512313), (NCT03857750).

Response to succinylcholine in patients carrying the K-variant of the butyrylcholinesterase gene.

BACKGROUND: Succinylcholine is usually metabolized quickly by the butyrylcholinesterase enzyme (BChE) but genetic variants of BChE may prolong the duration of action. The Kalow (K) variant is the most common mutation in the butyrylcholinesterase gene (BCHE), being present in 25% of Caucasians. The significance of the K-variant for the duration of action of succinylcholine has not been well studied. Our hypothesis was that the duration of action of succinylcholine would be prolonged in patients heterozygous for the K-variant genotype compared with the normal genotype (wild-type). METHODS: We included 70 adult surgical patients who received succinylcholine 1 mg/kg for rapid sequence induction. Neuromuscular monitoring was performed using ulnar nerve stimulation and acceleromyography. Duration of action of succinylcholine was defined as the time to 90% recovery of first twitch in train-of-four (T(1) 90%), BChE activity was determined, and the presence of BCHE K and A (atypical) variants were determined using DNA analysis. RESULTS: The wild-type BCHE was present in 38 patients, and 21 were heterozygous for the K-variant. Mean (SD) T(1) 90% in patients heterozygous for the K-variant, 11.6 (3.5) minutes, was longer than in patients with the wild-type genotype, 9.5 (2.7) minutes (P = 0.023), with a mean (95% confidence interval) difference of 2.1 (0.3-4.0) minutes. Patients heterozygous for the K-variant had a BChE activity of 5978 U/L compared with 7703 U/L in the wild-type group (P = 0.0045). CONCLUSION: We conclude that the mean duration of action of succinylcholine is prolonged for the patient heterozygous for the K-variant allele by at most 4 minutes relative to the wild-type, but this difference is small relative to the wide variability and overlap in recovery times among all patients.

There is no association between the circadian clock gene HPER3 and cognitive dysfunction after noncardiac surgery.

BACKGROUND: The specific clock-gene PERIOD3 is important with regard to circadian rhythmicity, sleep homeostasis, and cognitive function. The allele PER3(5/5) has been associated with worse cognitive performance in response to sleep deprivation. We hypothesized that patients with the PER3(5/5) genotype would have an increased risk of postoperative cognitive dysfunction (POCD) 1 week after noncardiac surgery. METHODS: Blood samples were analyzed from 93 patients with POCD and 186 patients without POCD from a completed multicenter study. The study population comprised patients ages 40 years and older undergoing noncardiac surgery who were tested preoperatively and 1 week after surgery with a neuropsychological test battery comprising 7 subtests. PER3 genotypes were determined by polymerase chain reaction analysis of DNA from blood samples (Clinicaltrials.gov identifier NCT01088100). RESULTS: The frequencies of the 3 genotypes were 11.8% (32 patients) PER3(5/5), 41.7% (113 patients) PER3(4/5), and 46.5% (126 patients) PER3(4/4). No significant difference was found in the distribution of the 3 genotypes according to POCD at 1 week (P = 0.68). Twelve percent (6% to 21%) of the patients with POCD and 12% (7% to 17%) of the patients without POCD had the PER3(5/5) genotype. The difference of the incidence of POCD/-POCD for the PER3(5/5) genotype was 1% (-7% to 10%). A significantly higher Z score was found in patients having the PER3(4/4) in 1 of the neuropsychological tests (error score of the Concept Shifting Test) (Bonferroni corrected P = 0.042). CONCLUSION: No significant association was found between the clock-gene PER3(5/5) genotype and POCD at 1 week after noncardiac surgery. If PER3(5/5) does worsen cognitive performance, the incidence is <10% of patients.

Airway management in unconscious non-trauma patients.

BACKGROUND: Tracheal intubation is recommended in unconscious trauma patients to protect the airway from pulmonary aspiration of gastric contents and also to ensure ventilation and oxygenation. Unconsciousness is often defined as a Glasgow Coma Scale (GCS) score below 9. In non-trauma patients, however, there are no such firm recommendations regarding airway management and the GCS score may be less useful. The aim of this study was to describe the authors' experience with airway management in unconscious non-trauma patients in the prehospital setting with a physician-manned Mobile Emergency Care Unit (MECU). The main focus of the study was on the need for subsequent tracheal intubation during hospitalisation after initial treatment. METHODS: The study was based on an analysis of data prospectively collected from the MECU database in Copenhagen, Denmark. All unconscious (GCS scores below 9) non-trauma patients registered in the database during 2006 were included. The ambulance patient charts and medical records were scrutinised to assess outcome and the need for tracheal intubation during the first 24 h after admittance into hospital. RESULTS: A total of 557 unconscious non-trauma patients were examined and 129 patients (23%) were tracheally intubated by the MECU physician before or during transport to the hospital. Intubation was done in most patients with cardiac arrest, severe stroke or respiratory failure. Of the remaining 428 patients, 364 (85%) regained consciousness before being transported to the hospital, whereas 64 patients remained unconscious during transport and 12 (19%) of these were intubated in the emergency department. CONCLUSIONS: The majority of unconscious non-trauma patients were not intubated in the prehospital setting. Unconscious non-trauma patients may not all need tracheal intubation before being transferred to hospital.

Distributing personal resuscitation manikins in an untrained population: how well are basic life support skills acquired?

BACKGROUND: Self-instruction with a DVD and a simple personal manikin is an effective alternative to traditional basic life support (BLS) courses. Objective To evaluate the effect of distributing DVD training kits to untrained laypersons. BLS skills were compared according to 2005 guidelines for resuscitation after 3.5 months with those obtained in untrained laypersons who completed the same course with instructor facilitation. METHODS: BLS skills of 55 untrained laypersons were assessed using the Laerdal ResusciAnne and PC Skill Reporting System in a 3 min test and a total score (12-48 points) was calculated. The participants received a DVD training kit without instructions. The test was repeated after 3.5 months. Data were compared with data from a previous published study where participants completed the same course in groups with instructor facilitation. RESULTS: There was no statistically significant difference in the total score after 3.5 months. The 'DVD-self-instructor' group obtained 33 (29-37) points and the 'DVD-with instructor' group obtained 34 (32-37) points, p=0.16. The 'DVD-with instructor' group performed significantly better in checking responsiveness and had a significantly shorter 'total hands-off time' (s) (85 (76-94) vs 96 (82-120), p=0.002) and delay until first compression or ventilation group (29 s (17-40) vs 33 s (22-48), p=0.04). CONCLUSIONS: Since no significant difference in total BLS score was found after 3.5 months between untrained laypersons who either completed a DVD-based BLS course in groups with instructor facilitation or received the same DVD training kit without instruction, the latter seems more efficient.

Prehospital triage of trauma patients before and after implementation of a regional triage guideline.

INTRODUCTION: Severely injured trauma patients have a considerable mortality rate. One way to reduce the mortality is to ensure optimal triage. The American College of Surgeons Committee on Trauma has since 1986 made guidelines for the triage of trauma patients. These guidelines formed the basis, when the capital region of Denmark implemented a regional trauma triage guideline on February 15th 2016. It is uncertain how the implementation of the regional trauma triage guideline has influenced the triage of trauma patients. The aim of this study was to investigate the changes in admission pattern of trauma patients in the entire region after the implementation of the regional trauma triage guideline. We hypothesized that there would be a reduction in the proportion of trauma patients admitted to the trauma center after the implementation of the regional trauma triage guideline. PATIENTS AND METHODS: In this observational cohort study with one-year follow-up, we used a national patient registry in Denmark. We identified trauma patients three years before and three years after the implementation of a new regional trauma triage guideline. The primary outcome was the proportion of trauma patients triaged to the regional trauma center. Secondary outcomes were: 30-day and one-year mortality, overtriage, and undertriage. RESULTS: We found a significant reduction in the proportion of trauma patients triaged to the trauma center from 2115/5951 (35.5%) to 1970/5857 (33.6%), after the implementation of the regional trauma triage guideline, the difference being 1.9% (95% CI: 0.19 to 3.6%); P = 0.03. Further, a significant reduction of overtriage from 15.4% to 9.5% (difference 5.9% with 95% CI of 3.8 to 7.9%) was found. No significant changes in undertriage, 30-day or one-year mortality were found (1.07% vs 0.97%, 4.3% vs 4.5%, and 15.7% vs 16.6% respectively). CONCLUSION: A significant decrease in the proportion of trauma patients admitted to the trauma center was found after implementation of a new regional trauma triage guideline. A reduction was seen in overtriage, but no changes were found in undertriage and both short-term and long-term mortality remained unchanged.

Time to CT scan for patients with acute severe neurological symptoms: a quality assurance study.

Emergent brain computed tomography (CT) scan allows for identification of patients presenting with acute severe neurological symptoms in whom medical and surgical interventions may be lifesaving. The aim of this study was to evaluate if time to CT from arrival at the emergency department exceeded 30 min in patients admitted with acute severe neurological symptoms. This was a retrospective register-based quality assurance study. We identified patients admitted to the emergency department with acute severe neurological symptoms between April 1st, 2016 and September 30th, 2020. Data were retrieved from the registry of acute medical team activations. We considered that time to CT from arrival at the emergency department should not exceed 30 min in more than 10% of patients. A total of 559 patients were included. Median time from arrival at the emergency department until CT scan was 24 min (IQR 16-35) in children (< 18 years), 10 min (IQR 7-17) for adults (18-59 years), and 11 min (IQR 7-16) for elders (> 60 years). This time interval exceeded 30 min for 8.2% (95% CI 6.1-10.9) of all included patients, 35.3% of children, 5.9% of adults, and 8.6% of elders. No children died within 30 days. The 30-day mortality was 21.3% (95% CI 16.4-27) in adults, and 43.9% (95% CI 38.2-49.8) in elders. Time from arrival at our emergency department until brain CT scan exceeded 30 min in 8.2% of all included patients but exceeded the defined quality aim in children and could be improved.