Resuscitation with an AED: putting the data to use.

The increased use of the automated external defibrillator (AED) contributes to the rising survival rate after sudden cardiac arrest in the Netherlands. When used, the AED records the unconscious person's medical data (heart rhythm and information about cardiopulmonary resuscitation), which may be important for further diagnosis and treatment. In practice, ethical and legal questions arise about what can and should be done with these 'AED data'. In this article, the authors advocate the development of national guidelines on the handling of AED data. These guidelines should serve two purposes: (1) to safeguard that data are handled carefully in accordance with data protection principles and the rules of medical confidentiality; and (2) to ensure nationwide availability of data for care of patients who survive resuscitation, as well as for quality monitoring of this care and for related scientific research. Given the medical ethical duties of beneficence and fairness, existing (sometimes lifesaving) information about AED use ought to be made available to clinicians and researchers on a structural basis. Creating a national AED data infrastructure, however, requires overcoming practical and organisational barriers. In addition, further legal study is warranted.

The challenges and possibilities of public access defibrillation.

Out-of-hospital cardiac arrest (OHCA) is a major health problem that affects approximately four hundred and thousand patients annually in the United States alone. It is a major challenge for the emergency medical system as decreased survival rates are directly proportional to the time delay from collapse to defibrillation. Historically, defibrillation has only been performed by physicians and in-hospital. With the development of automated external defibrillators (AEDs), rapid defibrillation by nonmedical professionals and subsequently by trained or untrained lay bystanders has become possible. Much hope has been put to the concept of Public Access Defibrillation with a massive dissemination of public available AEDs throughout most Western countries. Accordingly, current guidelines recommend that AEDs should be deployed in places with a high likelihood of OHCA. Despite these efforts, AED use is in most settings anecdotal with little effect on overall OHCA survival. The major reasons for low use of public AEDs are that most OHCAs take place outside high incidence sites of cardiac arrest and that most OHCAs take place in residential settings, currently defined as not suitable for Public Access Defibrillation. However, the use of new technology for identification and recruitment of lay bystanders and nearby AEDs to the scene of the cardiac arrest as well as new methods for strategic AED placement redefines and challenges the current concept and definitions of Public Access Defibrillation. Existing evidence of Public Access Defibrillation and knowledge gaps and future directions to improve outcomes for OHCA are discussed. In addition, a new definition of the different levels of Public Access Defibrillation is offered as well as new strategies for increasing AED use in the society.

The effect of the localisation of an underlying ST-elevation myocardial infarction on the VF-waveform: A multi-centre cardiac arrest study.

INTRODUCTION: In cardiac arrest, ventricular fibrillation (VF) waveform characteristics such as amplitude spectrum area (AMSA) are studied to identify an underlying myocardial infarction (MI). Observational studies report lower AMSA-values in patients with than without underlying MI. Moreover, experimental studies with 12-lead ECG-recordings show lowest VF-characteristics when the MI-localisation matches the ECG-recording direction. However, out-of-hospital cardiac arrest (OHCA)-studies with defibrillator-derived VF-recordings are lacking. METHODS: Multi-centre (Amsterdam/Nijmegen, the Netherlands) cohort-study on the association between AMSA, ST-elevation MI (STEMI) and its localisation. AMSA was calculated from defibrillator pad-ECG recordings (proxy for lead II, inferior vantage point); STEMI-localisation was determined using ECG/angiography/autopsy findings. RESULTS: We studied AMSA-values in 754 OHCA-patients. There were statistically significant differences between no STEMI, anterior STEMI and inferior STEMI (Nijmegen: no STEMI 13.0mVHz [7.9-18.6], anterior STEMI 7.5mVHz [5.6-13.8], inferior STEMI 7.5mVHz [5.4-11.8], p = 0.006. Amsterdam: 11.7mVHz [5.0-21.9], 9.6mVHz [4.6-17.2], and 6.9mVHz [3.2-16.0], respectively, p = 0.001). Univariate analyses showed significantly lower AMSA-values in inferior STEMI vs. no STEMI; there was no significant difference between anterior and no STEMI. After correction for confounders, adjusted absolute AMSA-values were numerically lowest for inferior STEMI in both cohorts, and the relative differences in AMSA between inferior and no STEMI was 1.4-1.7 times larger than between anterior and no STEMI. CONCLUSION: This multi-centre VF-waveform OHCA-study showed significantly lower AMSA in case of underlying STEMI, with a more pronounced difference for inferior than for anterior STEMI. Confirmative studies on the impact of STEMI-localisation on the VF-waveform are warranted, and might contribute to earlier diagnosis of STEMI during VF.

In vivo synthesis of meganuclease for generating transgenic zebrafish Danio rerio.

The authors show that co-injection at the one-cell stage of mRNA encoding a nuclear-targeted meganuclease I-SceI together with expression cassettes flanked by cognate restriction sites results in efficient stable transgenesis in zebrafish Danio rerio.

When is a bystander not a bystander any more? A European survey.

OBJECTIVE: There is international variation in the rates of bystander cardiopulmonary resuscitation (CPR). 'Bystander CPR' is defined in the Utstein definitions, however, differences in interpretation may contribute to the variation reported. The aim of this cross-sectional survey was to understand how the term 'bystander CPR' is interpreted in Emergency Medical Service (EMS) across Europe, and to contribute to a better definition of 'bystander' for future reference. METHODS: During analysis of the EuReCa ONE study, uncertainty about the definition of a 'bystander' emerged. Sixty scenarios were developed, addressing the interpretation of 'bystander CPR'. An electronic version of the survey was sent to 27 EuReCa National Coordinators, who distributed it to EMS representatives in their countries. Results were descriptively analysed. RESULTS: 362 questionnaires were received from 23 countries. In scenarios where a layperson arrived on scene by chance and provided CPR, up to 95% of the participants agreed that 'bystander CPR' had been performed. In scenarios that included community response systems, firefighters and/or police personnel, the percentage of agreement that 'bystander CPR' had been performed ranged widely from 16% to 91%. Even in scenarios that explicitly matched examples provided in the Utstein template there was disagreement on the definition. CONCLUSION: In this survey, the interpretation of 'bystander CPR' varied, particularly when community response systems including laypersons, firefighters, and/or police personnel were involved. It is suggested that the definition of 'bystander CPR' should be revised to reflect changes in treatment of OHCA, and that CPR before arrival of EMS is more accurately described.

Burning issues: early cooling of the brain after resuscitation using burn dressings. A proof of concept observation.

AIM OF THE STUDY: Early cooling of resuscitated patients improves neurological outcome. Out-of hospital initiation of cooling is uncommon however for mainly practical reasons. Using burn dressings in the out-of-hospital care could initiate brain cooling in an early stage and therefore be of value; the method is easily adaptable by ambulance crews. The influence of burn dressings on brain temperature is however unknown. We determined tympanic temperature changes as proxy for brain temperature in healthy volunteers after the application of cooling dressings to face and neck as a proof of concept study. METHOD: In 10 healthy human volunteers tympanic temperatures were measured in 30s intervals before, during and after the application of burn-dressings, special trauma burn-care dressings that are designed for the acute treatment of skin burns (Burnshield emergency burn care sterile trauma burn dressings, Burnshield Ltd., Wadefield, South Africa) for the duration of 20min for each episode. RESULTS: In all study subjects the tympanic temperature was significantly lowered after 20min of the application of the burnshields. The mean difference between baseline and 2nd half of the exposure period was 0.43 degrees C (p<0.0001), ranging from 0.10 to 1.18 degrees C. CONCLUSION: Burn dressings could be of value in the early initiation of brain cooling in resuscitated patients. This study warrants further research to the effect of burnshield dressings on neurological activity and the effect on outcome after resuscitation.

Direct imaging of in vivo neuronal migration in the developing cerebellum.

The upper rhombic lip (URL), a germinal zone in the dorsoanterior hindbrain, has long been known to be a source for neurons of the vertebrate cerebellum. It was thought to give rise to dorsally migrating granule cell precursors (Figure 1e); however, recent fate mapping studies have questioned the exclusive contributions of the URL to granule cells. By taking advantage of the clarity of the zebrafish embryo during the stages of brain morphogenesis, we have followed the fate of neuronal precursor cells generated within the upper rhombic lip directly. Combining a novel GFP labeling strategy with in vivo time-lapse imaging, we find, contrary to the former view, that most URL-descendants migrate anterior toward the midhindbrain boundary (MHB) and then course ventrally along the MHB (Figure 1f). As the migrating neuronal precursors reach the MHB, they form ventrally extending projections, likely axons, and continue ventral migration to settle outside of the cerebellum, in the region of the ventral brainstem. Thus, we define a new pathway for URL-derived neuronal precursor cells consistent with the recent fate maps. In addition, our results strongly suggest that the MHB plays a crucial role, not only in induction and patterning of the cerebellar anlage, but also in organizing its later morphogenesis by influencing cell migration.

[Arguments in support of the implementation of the new guidelines for cardio-pulmonary resuscitation in the Netherlands]. / Argumenten voor de invoering van de vernieuwde reanimatierichtlijnen in Nederland.

The implementation of the new guidelines for cardiopulmonary resuscitation in the Netherlands has been questioned with reference to the expected low cost-effectiveness. The implementation is based on the best available evidence, derived from studies that addressed the specific activities of lay rescuers as well as professionals, but not on studies that integrate all changes in the process, from initial actions of lay rescuers to the last elements of in-hospital management. Therefore, the efficacy of new guidelines cannot be evaluated prior to wide-scale implementation. It is not possible to calculate cost-effectiveness before guidelines are introduced, as controlled studies at population level are not feasible. For this reason, the decision to introduce the new guidelines cannot be based on ideal evidence, with survival as a measure of outcome. Effectiveness can be studied only after full introduction of the procedure, as was demonstrated when the previous guidelines were introduced in 2002. Cost-effectiveness is not a relevant issue, as the cost of implementation of guideline changes to lay rescuers has no impact on the budget for healthcare. In addition, the revision concerns items such as the recognition of circulatory arrest, the balance of thoracic compression versus ventilation and the use of the automatic external defibrillator, which are expected to be very effective. Hence, the implementation of the new guidelines for cardio-pulmonary resuscitation in the Netherlands is justified.

Doppler left ventricular flow pattern versus conventional predictors of left ventricular thrombus after acute myocardial infarction.

OBJECTIVES: The value of Doppler-derived left ventricular spatial flow patterns in predicting left ventricular thrombus formation after myocardial infarction was compared with that of conventional clinical and echocardiographic variables. BACKGROUND: Assessment of left ventricular thrombosis risk after myocardial infarction is important because of potential embolic sequelae that are reduced by oral anticoagulant agents. METHODS: Clinical, two-dimensional and Doppler echocardiographic data were prospectively obtained in 104 patients with acute myocardial infarction within 48 h of admission. Ventricular flow was assessed by Doppler echocardiography and considered normal when brisk ventricular inflow with simultaneous onset at the mitral valve and apical levels was present, together with alternating directions of apical flow throughout the cardiac cycle. In addition to normal flow, two abnormal flow patterns were recognized: apical rotating flow and vortex ring formation. Oral anticoagulant agents were prescribed only to patients with abnormal flow at admission. The incidence of left ventricular thrombosis was assessed by echocardiography during 9 months of follow-up. RESULTS: Abnormal flow pattern had a positive predictive value of 63% and a negative predictive value of 99%. On stepwise logistic regression analysis, only abnormal flow pattern had an independent relation to left ventricular thrombus (odds ratio 92). CONCLUSIONS: Left ventricular flow pattern derived by Doppler echocardiography soon after admission is superior to conventional clinical and two-dimensional echocardiographic assessment in estimating the risk of left ventricular thrombosis after myocardial infarction.

Diagnostic accuracy of transesophageal echocardiography during cardiopulmonary resuscitation.

OBJECTIVES: We sought to establish the diagnostic accuracy of transesophageal echocardiography (TEE) during cardiopulmonary resuscitation. BACKGROUND: Because of its bedside diagnostic capabilities, excellent cardiac images and lack of interference with resuscitation efforts, TEE is ideally suited to determine the cause of a circulatory arrest that is not due to severe arrhythmia. However, the diagnostic accuracy of TEE during resuscitation is unknown. METHODS: TEE was performed in patients with prolonged circulatory arrest. The TEE diagnoses were compared with diagnoses from autopsy, surgery and clinical follow-up. RESULTS: Of the 48 study patients (29 male, 19 female, mean age +/- SD 61 +/- 20 years), 28 had an in-hospital cardiac arrest and 20 an out-of-hospital onset of arrest. Forty-four patients eventually died; four survived to discharge. The diagnoses made with TEE were cardiac tamponade (n = 6), myocardial infarction (n = 21), pulmonary embolism (n = 6), ruptured aorta (n = 1), aortic dissection (n = 4), papillary muscle rupture (n = 1), other diagnosis (n = 2) and absence of structural cardiac abnormalities (n = 7). A definite diagnosis from a reference standard was available in 31 patients. The TEE diagnosis was confirmed in 27 of the 31-by postmortem examination (n = 19), operation (n = 2), angiography (n = 2) or clinical course (n = 4). In the other four patients the TEE diagnosis proved incorrect by postmortem examination. The sensitivity, specificity and positive predictive value of TEE were 93%, 50% and 87%, respectively. In 15 patients (31%), major therapeutic decisions were based on TEE findings. CONCLUSIONS: TEE can reliably establish the cause of a circulatory arrest during cardiopulmonary resuscitation.

Ectopic Sox3 activity elicits sensory placode formation.

The induction of sensory organ placodes, in particular the lens placode, represents the paradigm for induction. We show that medaka Sox3 is expressed in the neuroectoderm and in the placodes of all sensory organs prior to placode formation and subsequently in placode-derived tissues. Ectopic Sox3 expression leads to ectopic expression of Pax6 and Eya1 in embryonic ectoderm and causes ectopic lens and otic vesicle formation. The descendants of cells ectopically expressing Sox3-mRNA contribute to ectopic lens tissue. This suggests a permissive role for Sox3 in establishing a placodal competence. In addition, ectopic Sox3 expression leads to the dysgenesis of the endogenous sensory organs. Both effects of ectopic Sox3 expression can be separated by ectopic expression of a truncated Sox3 variant depending on its expression level. Our data suggests that Sox3 is a permissive factor for sensory placode formation and plays an important role in sensory organ development.

Six3, a medaka homologue of the Drosophila homeobox gene sine oculis is expressed in the anterior embryonic shield and the developing eye.

The conserved transcription factor Pax6 is essential for eye development in Drosophila and mammals (Hill, R.E., Favor, J., Hogan, B.L.M., Ton, C.C.T., Saunders, G.F., Hanson, I.M., Prosser, J., Jordan, T., Hastie, N.D., van Heyningen, V., 1991. Mouse small eye results from mutations in a paired-like homeobox containing gene. Nature 354, 522-525; Ton, C., Hirvonen, H., Miwa, H., Weil, M., Monaghan, P., Jordan, T., van Heyningen, V., Hastie, N., Meijers-Heijboer, H., Drechsler, M., Royer-Pokora, B., Collins, F., Swaroop, A., Strong, L.C., Saunders, G.F., 1991. Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. Cell 6, 1059-1074; Matsuo, T., Osumi-Yamashita, N., Noji, S., Ohuchi, H., Koyama, E., Myokai, F., Matsuo, N., Toniguchi, S., Dari, H., Jseki, S., Ninomiya, Y., Fujiwara, M., Watanabe, T., Eto, K., 1993. A mutation at the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nature genet. 3, 299-304; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785-789). These findings led to the hypothesis that additional genes involved in invertebrate and vertebrate eye development are structurally and functionally conserved (Halder, G., Callaerts, P., Gehring, W.J., 1995. New perspectives on eye evolution. Curr. Opin. Gen. Dev. 5, 602-609; Quiring, R., Walldorf, U., Kloter, U., Gehring, W.J., 1994. Homology of the eyeless gene of Drosophila to the small eye gene in mice and aniridia in humans. Science 265, 785-789). Candidates for such conserved genes are the Drosophila homeobox gene sine oculis (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron l2, 977-996) and its murine homologue Six3 (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). sine oculis (so) is essential for the development of the larval and adult visual system (Cheyette, B.N.R., Green, P.J., Martin, K., Garren, H., Hartenstein, V., Zipursky, S.L., 1994. The Drosophila sine oculis locus encodes a homeodomain-containing protein required for the development of the entire visual system. Neuron l2, 977-996). Six3 is expressed in the anterior neural plate and optic vesicles, lens, olfactory placodes and ventral forebrain (Oliver, G., Mailhos, A., Wehr, R., Copeland, N.G., Jenkins, N.A., Gruss, P., 1995. Six3, a murine homologue of the sine oculis gene, demarcates the most anterior border of the developing neural plate and is expressed during eye development. Development 121, 4045-4055). Overexpression of mouse Six3 gene in medaka fish embryos (Orvzias latipes) results in the formation of an ectopic lens, indicating that Six3 activity can trigger the genetic pathway leading to lens formation (Oliver, G., Loosli, F., Koster, R., Wittbrodt, J., Gruss, P., 1996. Ectopic lens induction in fish in response to the murine homeobox gene Six3. Mech. Dev. 60, 233-239). We isolated the medaka Six3 homologue and analyzed its expression pattern in the medaka embryo. It is expressed initially in the anterior embryonic shield and later in the developing eye and prosencephalon. The early localized expression of Six3 suggests a role in the regionalization of the rostral head.

A genetic screen for mutations affecting embryonic development in medaka fish (Oryzias latipes).

In a pilot screen, we assayed the efficiency of ethylnitrosourea (ENU) as a chemical mutagen to induce mutations that lead to early embryonic and larval lethal phenotypes in the Japanese medaka fish, Oryzias latipes. ENU acts as a very efficient mutagen inducing mutations at high rates in germ cells. Three repeated treatments of male fish in 3 mM ENU for 1 h results in locus specific mutation rates of 1.1-1.95 x10(-3). Mutagenized males were outcrossed to wild type females and the F1 offspring was used to establish F2 families. F2 siblings were intercrossed and the F3 progeny was scored 24, 48 and 72 h after fertilization for morphological alterations affecting eye development. The presented mutant phenotypes were identified using morphological criteria and occur during early developmental stages of medaka. They are stably inherited in a Mendelian fashion. The high efficiency of ENU to induce mutations in this pilot screen indicates that chemical mutagenesis and screening for morphologically visible phenotypes in medaka fish allows the genetic analysis of specific aspects of vertebrate development complementing the screens performed in other vertebrate model systems.

Quality of survival after cardiopulmonary resuscitation.

BACKGROUND: Outcome of cardiopulmonary resuscitation (CPR) can be poor, in terms of life expectancy and quality of life. OBJECTIVES: To determine the impact of patient characteristics before, during, and after CPR on these outcomes, and to compare results of the quality-of-life assessment with published studies. METHODS: In a cohort study, we assessed by formal instruments the quality of life, cognitive functioning, depression, and level of dependence of survivors after inhospital CPR. Follow-up was at least 3 months after discharge from the hospital (tertiary care center). RESULTS: Of 827 resuscitated patients, 12% (n = 101) survived to follow-up. Of the survivors, 89% participated in the study. Most survivors were independent in daily life (75%), 17% were cognitively impaired, and 16% had depressive symptoms. Multivariate regression analysis showed that quality of life and cognitive function were determined by 2 factors known before CPR-the reason for admission and age. Factors during and after resuscitation, such as prolonged cardiac arrest and coma, did not significantly determine the quality of life or cognitive functioning of survivors. The quality of life of our CPR survivors was worse compared with a reference group of elderly individuals, but better than that of a reference group of patients with stroke. The quality of life did not importantly differ between the compared studies of CPR survivors. CONCLUSIONS: Cardiopulmonary resuscitation is frequently unsuccessful, but if survival is achieved, a relatively good quality of life can be expected. Quality of life after CPR is mostly determined by factors known before CPR. These findings may be helpful in informing patients about the outcomes of CPR.