Screening for Rare Coding Variants That Associate With the QTc Interval in Iceland.

Background Long-QT syndrome (LQTS) is a cardiac repolarization abnormality that can lead to sudden cardiac death. The most common causes are rare coding variants in the genes KCNQ1, KCNH2, and SCN5A. The data on LQTS epidemiology are limited, and information on expressivity and penetrance of pathogenic variants is sparse. Methods and Results We screened for rare coding variants associated with the corrected QT (QTc) interval in Iceland. We explored the frequency of the identified variants, their penetrance, and their association with severe events. Twelve variants were associated with the QTc interval. Five in KCNQ1, 3 in KCNH2, 2 in cardiomyopathy genes MYBPC3 and PKP2, and 2 in genes where coding variants have not been associated with the QTc interval, ISOC1 and MYOM2. The combined carrier frequency of the 8 variants in the previously known LQTS genes was 530 per 100 000 individuals (1:190). p.Tyr315Cys and p.Leu273Phe in KCNQ1 were associated with having a mean QTc interval longer than 500 ms (P=4.2×10-7; odds ratio [OR], 38.6; P=8.4×10-10, OR, 26.5; respectively), and p.Leu273Phe was associated with sudden cardiac death (P=0.0034; OR, 2.99). p.Val215Met in KCNQ1 was carried by 1 in 280 Icelanders, had a smaller effect on the QTc interval (P=1.8×10-44; effect, 22.8 ms), and did not associate with severe clinical events. Conclusions The carrier frequency of associating variants in LQTS genes was higher than previous estimates of the prevalence of LQTS. The variants have variable effects on the QTc interval, and carriers of p.Tyr315Cys and p.Leu273Phe have a more severe disease than carriers of p.Val215Met. These data could lead to improved identification, risk stratification, and a more precise clinical approach to those with QTc prolongation.

Opioids for Treatment of Pre-hospital Acute Pain: A Systematic Review.

INTRODUCTION: Acute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies. METHODS: The PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method. RESULTS: A total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine. CONCLUSIONS: Available evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups.

Ketamine for the treatment of prehospital acute pain: a systematic review of benefit and harm.

BACKGROUND: Few publications have addressed prehospital use of ketamine in analgesic doses. We aimed to assess the effect and safety profile of ketamine compared with other analgesic drugs (or no drug) in adult prehospital patients with acute pain. METHODS: A systematic review of clinical trials assessing prehospital administration of ketamine in analgesic doses compared with other analgesic drugs or no analgesic treatment in adults. We searched PubMed, EMBASE, Cochrane Library and Epistemonikos from inception until 15 February 2020, including relevant articles in English and Nordic languages. We used the Cochrane and Grading of Recommendations Assessment, Development and Evaluation methodologies and exclusively assessed patient-centred outcomes. Two independent authors screened trials for eligibility, extracted data and assessed risk of bias. RESULTS: We included eight studies (2760 patients). Ketamine was compared with various opioids given alone, and intranasal ketamine given with nitrous oxide was compared with nitrous oxide given alone. Four randomised controlled trials (RCTs) and one cluster randomised trial included 699 patients. One prospective cohort included 27 patients and two retrospective cohorts included 2034 patients. Five of the eight studies had high risks of bias. Pain score with ketamine is probably lower than after opioids as demonstrated in a cluster-RCT (308 patients) and a retrospective cohort (158 patients) study, Δvisual analogue scale -0.4 (-0.8 to 0.0) and Δnumeric pain rating scale -3.0 (-3.86 to -2.14), respectively. Ketamine probably leads to less nausea and vomiting (risk ratio (RR) 0.24 (0.11 to 0.52)) but more agitation (RR 7.81 (1.85 to 33)) than opioids. CONCLUSIONS: This systematic literature review finds that ketamine probably reduces pain more than opioids and with less nausea and vomiting but higher risk of agitation. Risk of bias in included studies is high. OTHER: Scandinavian society of anaesthesiology and intensive care medicine funded meetings and software. The Norwegian Air Ambulance Foundation funded publication. Otherwise this research received no grant from any agency in the public, commercial or not-for-profit sectors. PROSPERO REGISTRATION NUMBER: CRD42018114399.

Femoral nerve blocks for the treatment of acute pre-hospital pain: A systematic review with meta-analysis.

BACKGROUND: Pain management is one of the most important interventions in the emergency medical services. The femoral nerve block (FNB) is, among other things, indicated for pre- and post-operative pain management for patients with femoral fractures but its role in the pre-hospital setting has not been determined. The aim of this review was to assess the effect and safety of the FNB in comparison to other forms of analgesia (or no treatment) for managing acute lower extremity pain in adult patients in the pre-hospital setting. METHODS: A systematic review (PROSPERO registration (CRD42018114399)) was conducted. The Cochrane and GRADE methods were used to assess outcomes. Two authors independently reviewed each study for eligibility, extracted the data and performed risk of bias assessments. RESULTS: Four studies with a total of 252 patients were included. Two RCTs (114 patients) showed that FNB may reduce pain more effectively than metamizole (mean difference 32 mm on a 100 mm VAS (95% CI 24 to 40)). One RCT (48 patients) compared the FNB with lidocaine and magnesium sulphate to FNB with lidocaine alone and was only included here for information regarding adverse effects. One case series included 90 patients. Few adverse events were reported in the included studies. The certainty of evidence was very low. We found no studies comparing FNB to inhaled analgesics, opioids or ketamine. CONCLUSIONS: Evidence regarding the effectiveness and adverse effects of pre-hospital FNB is limited. Studies comparing pre-hospital FNB to inhaled analgesics, opioids or ketamine are lacking.

Identifying out-of-hospital cardiac arrest patients with no chance of survival: An independent validation of prediction rules.

BACKGROUND: The Basic life support (BLS) and Advanced life support (ALS) are known prediction rules for termination of resuscitation (TOR) in out-of-hospital cardiac arrest (OHCA). Recently, a new rule was developed by Jabre et al. We aimed to independently validate and compare the predictive accuracy of these rules. METHODS: OHCA cases in Iceland from 2008 to 2017 from a population-based, prospectively registered database. Primary outcome was survival to discharge among patients that met all conditions of abovementioned rules: BLS (not witnessed by EMS personnel, no defibrillation nor ROSC before transport), ALS (BLS criteria plus not witnessed nor CPR by bystander) and Jabre (not witnessed by EMS personnel, initial rhythm non-shockable, no sustainable ROSC before third dose of adrenaline). RESULTS: Overall, 568 OHCA patients were included in validation of TOR rules. Mean age 67, males 74%, witnessed by EMS 11%, by bystander 66% that attempted CPR in 50%, transported to hospital 60%, overall survival 20%. All rules had high specificity for mortality, 99.6-100% (95%CI 95-100). The Jabre and BLS rules had similar sensitivity 47% (43-52) vs. 44% (40-49), respectively, the sensitivity of ALS was lower, 8% (5-11). Combined use of positive BLS and Jabre rules performed the best, identifying 88/226 (39%) of futile cases transported to hospital, specificity 100% (97-100) and sensitivity 59% (55-64). CONCLUSIONS: The accuracy of the BLS and Jabre TOR rules to predict mortality after OHCA is very good and their combined use may be superior to the use of either one.

Reporting Helicopter Emergency Medical Services in Major Incidents: A Delphi Study.

OBJECTIVE: Research on helicopter emergency medical services (HEMS) in major incidents is predominately based on case descriptions reported in a heterogeneous fashion. Uniform data reported with a consensus-based template could facilitate the collection, analysis, and exchange of experiences. This type of database presently exists for major incident reporting at www.majorincidentreporting.net. This study aimed to develop a HEMS-specific major incident template. METHODS: This Delphi study included 17 prehospital critical care physicians with current or previous HEMS experience. All participants interacted through e-mail. We asked these experts to define data variables and rank which were most important to report during an immediate prehospital medical response to a major incident. Five rounds were conducted. RESULTS: In the first round, the experts suggested 98 variables. After 5 rounds, 21 variables were determined by consensus. These variables were formatted in a template with 4 main categories: HEMS background information, the major incident characteristics relevant to HEMS, the HEMS response to the major incident, and the key lessons learned. CONCLUSION: Based on opinions from European experts, we established a consensus-based template for reporting on HEMS responses to major incidents. This template will facilitate uniformity in the collection, analysis, and exchange of experience.

[Transport and treatment of patients with STEMI in rural Iceland--Only a few patients receive PPCI within 120 minutes]. / Flutningstími og gæði meðferðar hjá sjúklingum með ST-hækkunar-hjartadrep á landsbyggðinni--fair ná í kransæðavíkkun innan 120 mínútna.

INTRODUCTION: ST-segment Elevation Myocardial Infarction (STEMI) is a life-threatening disease and good outcome depends on early restoration of coronary blood flow. Primary percutaneous coronary intervention (PPCI) is the treatment of choice if performed within 120 minutes of first medical contact (FMC) but in case of anticipated long transport or delays, pre-hospital fibrinolysis is indicated. The aim was to study transport times and adherence to clinical guidelines in patients with STEMI transported from outside of the Reykjavik area to Landspitali University Hospital in Iceland. MATERIALS AND METHODS: Retrospective chart review was conducted of all patients diagnosed with STEMI outside of the Reykjavik area and transported to Landspitali University Hospital in Reykjavik in 2011-2012. Descriptive statistical analysis and hypothesis testing was applied. RESULTS: Eighty-six patients had signs of STEMI on electrocardiogram (ECG) at FMC. In southern Iceland nine patients (21%) underwent PPCI within 120 minutes (median 157 minutes) and no patient received fibrinolysis. In northern Iceland and The Vestman Islands, where long transport times are expected, 96% of patients eligible for fibrinolysis (n=31) received appropriate therapy in a median time of 57 minutes. Significantly fewer patients received appropriate anticoagulation treatment with clopidogrel and enoxaparin in southern Iceland compared to the northern part. Mortality rate was 7% and median length of stay in hospital was 6 days. CONCLUSIONS: Time from FMC to PPCI is longer than 120 minutes in the majority of cases. Pre-hospital fibrinolysis should be considered as first line treatment in all parts of Iceland outside of the Reykjavik area. Directly electronically transmitted ECGs and contact with cardiologist could hasten diagnosis and decrease risk of unnecessary interhospital transfer. A STEMI database should be established in Iceland to facilitate quality control.

Does turning trauma patients with an unstable spinal injury from the supine to a lateral position increase the risk of neurological deterioration?--A systematic review.

BACKGROUND: Airway protection and spinal precautions are competing concerns in the treatment of unconscious trauma patients. The placement of such patients in a lateral position may facilitate the acquisition of an adequate airway. However, trauma dogma dictates that patients should be transported in the supine position to minimize spinal movement. In this systematic review, we sought to answer the following question: Given an existing spinal injury, will changing a patient's position from supine to lateral increase the risk of neurological deterioration? METHODS: The review protocol was published in the PROSPERO database (Reg. no. CRD42012001190). We performed literature searches in PubMed, Medline, EMBASE, the Cochrane Library, CINAHL and the British Nursing Index and included studies of traumatic spinal injury, lateral positioning and neurological deterioration. The search was updated prior to submission. Two researchers independently completed each step in the review process. RESULTS: We identified 1,164 publications. However, none of these publications reported mortality or neurological deterioration with lateral positioning as an outcome measure. Twelve studies used movement of the injured spine with lateral positioning as an outcome measure; eleven of these investigations were cadaver studies. All of these cadaver studies reported spinal movement during lateral positioning. The only identified human study included eighteen patients with thoracic or lumbar spinal fractures; according to the study authors, the logrolling technique did not result in any neurological deterioration among these patients. CONCLUSIONS: We identified no clinical studies demonstrating that rotating trauma patients from the supine position to a lateral position affects mortality or causes neurological deterioration. However, in various cadaver models, this type of rotation did produce statistically significant displacements of the injured spine. The clinical significance of these cadaver-based observations remains unclear. The present evidence for harm in rotating trauma patients from the supine position to a lateral position, including the logroll maneuver, is inconclusive.

Is the supine position associated with loss of airway patency in unconscious trauma patients? A systematic review and meta-analysis.

BACKGROUND: Airway compromise is a leading cause of death in unconscious trauma patients. Although endotracheal intubation is regarded as the gold standard treatment, most prehospital providers are not trained to perform ETI in such patients. Therefore, various lateral positions are advocated for unconscious patients, but their use remains controversial in trauma patients. We conducted a systematic review to investigate whether the supine position is associated with loss of airway patency compared to the lateral position. METHODS: The review protocol was published in the PROSPERO database (Reg. no. CRD42012001190). We performed literature searches in PubMed, Medline, EMBASE, Cochrane Library, CINAHL and British Nursing Index and included studies related to airway patency, reduced level of consciousness and patient position. We conducted meta-analyses, where appropriate. We graded the quality of evidence with the GRADE methodology. The search was updated in June 2014. RESULTS: We identified 1,306 publications, 39 of which were included for further analysis. Sixteen of these publications were included in meta-analysis. We did not identify any studies reporting direct outcome measures (mortality or morbidity) related to airway compromise caused by the patient position (lateral vs. supine position) in trauma patients or in any other patient group. In studies reporting only indirect outcome measures, we found moderate evidence of reduced airway patency in the supine vs. the lateral position, which was measured by the apnea/hypopnea index (AHI). For other indirect outcomes, we only found low or very low quality evidence. CONCLUSIONS: Although concerns other than airway patency may influence how a trauma patient is positioned, our systematic review provides evidence supporting the long held recommendation that unconscious trauma patients should be placed in a lateral position.

Physician experience in addition to ACLS training does not significantly affect the outcome of prehospital cardiac arrest.

BACKGROUND: Little data exists on whether the physicians' skills in responding to cardiac arrest are fully developed after the advanced cardiac life support (ACLS) course, or if there is a significant improvement in their performance after an initial learning curve. OBJECTIVE: To estimate the effect of physician experience on the results of prehospital cardiac arrests. MATERIALS AND METHODS: Prospective data were collected on all prehospital resuscitative attempts in the area by ACLS-trained ambulance physicians. RESULTS: Of 232 attempted cardiac resuscitations, 96 (41%) patients survived to hospital admission and 44 (19%) were discharged alive. A group of 39 physicians responded to from one up to 29 cases with a mean of four cases. Physicians responding to five or fewer cases had a trend to fewer patients surviving to admission compared with those responding to six or more (36 vs. 45%, P=0.31) but no difference was found on survival to discharge (19 vs. 20%, P=0.87). CONCLUSION: In this study, resuscitative experience of the physician did not have a significant effect on survival suggesting that experience does not significantly add to the current ACLS training in responding to ventricular fibrillation/ventricular tachycardia. More studies are needed.

[Prehospital cardiac life support in the Reykjavík area 1999-2002]. / Endurlífgunartilraunir utan sjúkrahúsa á höfudborgarsvaedinu 1999-2002.

OBJECTIVES: A physician manned ambulance has provided advanced resuscitation service in the Reykjavík area for over 20 years. Out of hospital resuscitation since 1982 has been done with average response time of 4.6-4.9 minutes, the survival rate to hospital admission has been 31-40% and survival to hospital discharge 16-17%. In the years preceding this study, several changes were done in the service; the service area was enlarged, dispatch was centralized to one emergency number, the training of EMT s and physicians was improved and a two-tier rendezvous system was adopted. Cell phone coverage reached over 90% of the population. The study was done in 1999-2002 with the objective to: 1. measure the results of attempted prehospital resuscitations for cardiac diseases in the area, 2. to monitor the effect of bystander response, 3. to estimate the effect of changes in the service prior to the study period. MATERIALS AND METHODS: A ambulance staffed with EMTs and one with a physician were dispatched to all possible cases of cardiac arrest. Resuscitation was attempted using the AHA guidelines for resuscitation. Prospective data was collected following the Utstein template recorded by the physician on call. RESULTS: A total of 319 resuscitative attempts were made during the years 1999-2002, excluding hanging, SIDS, drowning, suicide, trauma, internal bleeding and other diseases, a total of 232 arrests were considered of cardiac origin giving an incidence of 33/100,000/year. The average response time was 6,1 min. Of 232 cardiac resuscitation attempts 140 patients (60%) were in VF/VT, 53 (23%) in asystole and 39 (17%) in other rhythms. Ninety-six (41%) of all patients survived being admitted to hospital ward and 44 (19%) survived to discharge with 39 being alive at 12 months. Of patients in VF/VT, 79 (56%) survived to hospital admission and 39 (28%) to hospital discharge. Resuscitation was more successful in cases of witnessed arrest and if CPR was attempted by bystanders. CONCLUSION: Despite various changes in the EMS system, the results of resuscitative attempts are similar to previous studies in the area but an increased proportion of survivors is left with neurological damage. In 54% of the cases COR was performed by bystanders. Response time needs to be shortened and CPR training increased.