| 1. |
- Friberg, Hans, et al.
(author)
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Internationell och nationell konsensus om bästa vård efter hävt hjärtstopp. Många patienter blir helt återställda.
- 2010
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In: Läkartidningen. - 0023-7205 .- 1652-7518. ; 107:8, s. 2-514
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Research review (peer-reviewed)abstract
- An international consensus report on postresuscitation care after cardiac arrest has recently been published. Its content and main messages are in line with the recommendations from The Swedish Resuscitation Council, which include: diagnosing and treating the underlying disease, offering good general intensive care, considering hypothermia treatment, standardising prognostication and follow-up.
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| 2. |
- Nielsen, Niklas, et al.
(author)
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Detailed statistical analysis plan for the target temperature management after out-of-hospital cardiac arrest trial
- 2013
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In: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 14
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Journal article (peer-reviewed)abstract
- Background: Animal experimental studies and previous randomized trials suggest an improvement in mortality and neurological function with temperature regulation to hypothermia after cardiac arrest. According to a systematic review, previous trials were small, had a risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management (TTM) strategy is not known. To prevent outcome reporting bias, selective reporting and data-driven results, we present the a priori defined detailed statistical analysis plan as an update to the previously published outline of the design and rationale for the TTM trial. Methods: The TTM trial is an investigator-initiated, multicenter, international, randomized, parallel-group, and assessor-blinded clinical trial of temperature management in 950 adult unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients are randomized to a TTM of either 33 degrees C or 36 degrees C after return of spontaneous circulation. The primary outcome is all-cause mortality at maximal follow-up (until end of the trial and a minimum of 180 days). The main secondary outcomes are the composite outcome of all-cause mortality and poor neurological function (Cerebral Performance Category (CPC) 3 and 4, and modified Rankin Scale (mRS) 4 and 5) at hospital discharge and at 180 days; and assessment of safety and harm: bleeding, infections, electrolyte and metabolic disorders, seizures, cardiac arrhythmia, and renal replacement therapy. Conclusion: The TTM trial investigates potential benefit and harm of two target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
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| 3. |
- Nielsen, Niklas, et al.
(author)
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Targeted Temperature Management at 33 degrees C versus 36 degrees C after Cardiac Arrest
- 2013
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In: New England Journal of Medicine. - 0028-4793. ; 369:23, s. 2197-2206
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Journal article (peer-reviewed)abstract
- BackgroundUnconscious survivors of out-of-hospital cardiac arrest have a high risk of death or poor neurologic function. Therapeutic hypothermia is recommended by international guidelines, but the supporting evidence is limited, and the target temperature associated with the best outcome is unknown. Our objective was to compare two target temperatures, both intended to prevent fever. MethodsIn an international trial, we randomly assigned 950 unconscious adults after out-of-hospital cardiac arrest of presumed cardiac cause to targeted temperature management at either 33 degrees C or 36 degrees C. The primary outcome was all-cause mortality through the end of the trial. Secondary outcomes included a composite of poor neurologic function or death at 180 days, as evaluated with the Cerebral Performance Category (CPC) scale and the modified Rankin scale. ResultsIn total, 939 patients were included in the primary analysis. At the end of the trial, 50% of the patients in the 33 degrees C group (235 of 473 patients) had died, as compared with 48% of the patients in the 36 degrees C group (225 of 466 patients) (hazard ratio with a temperature of 33 degrees C, 1.06; 95% confidence interval [CI], 0.89 to 1.28; P=0.51). At the 180-day follow-up, 54% of the patients in the 33 degrees C group had died or had poor neurologic function according to the CPC, as compared with 52% of patients in the 36 degrees C group (risk ratio, 1.02; 95% CI, 0.88 to 1.16; P=0.78). In the analysis using the modified Rankin scale, the comparable rate was 52% in both groups (risk ratio, 1.01; 95% CI, 0.89 to 1.14; P=0.87). The results of analyses adjusted for known prognostic factors were similar. ConclusionsIn unconscious survivors of out-of-hospital cardiac arrest of presumed cardiac cause, hypothermia at a targeted temperature of 33 degrees C did not confer a benefit as compared with a targeted temperature of 36 degrees C. (Funded by the Swedish Heart-Lung Foundation and others; TTM ClinicalTrials.gov number, NCT01020916.)
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| 4. |
- Cronberg, Tobias, et al.
(author)
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Neuron-specific enolase correlates with other prognostic markers after cardiac arrest.
- 2011
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In: Neurology. - 1526-632X. ; 77:7, s. 623-630
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Journal article (peer-reviewed)abstract
- OBJECTIVE: Therapeutic hypothermia (TH) is a recommended treatment for survivors of cardiac arrest. Prognostication is complicated since sedation and muscle relaxation are used and established indicators of a poor prognosis are lacking. This prospective, observational study describes the pattern of commonly used prognostic markers in a hypothermia-treated cohort of cardiac arrest patients with prolonged coma. METHODS: Among 111 consecutive patients, 19 died, 58 recovered, and 34 were in coma 3 days after normothermia (4.5 days after cardiac arrest), defined as prolonged coma. All patients were monitored with continuous amplitude-integrated EEG and repeated samples of neuron-specific enolase (NSE) were collected. In patients with prolonged coma, somatosensory evoked potentials (SSEP) and brain MRI were performed. A postmortem brain investigation was undertaken in patients who died. RESULTS: Six of the 17 patients (35%) with NSE levels <33 μg/L at 48 hours regained the capacity to obey verbal commands. By contrast, all 17 patients with NSE levels >33 failed to recover consciousness. In the >33 NSE group, all 10 studied with MRI had extensive brain injury on diffusion-weighted images, 12/16 lacked cortical responses on SSEP, and all 6 who underwent autopsy had extensive severe histologic damage. NSE levels also correlated with EEG pattern, but less uniformly, since 11/17 with NSE <33 had an electrographic status epilepticus (ESE), only one of whom recovered. A continuous EEG pattern correlated to NSE <33 and awakening. CONCLUSIONS: NSE correlates well with other markers of ischemic brain injury. In patients with no other signs of brain injury, postanoxic ESE may explain a poor outcome.
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| 5. |
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| 6. |
- Godbolt, Alison K, et al.
(author)
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Långvarig svår medvetandestörning efter hjärnskada hos vuxna : nya rekommendationer ger underlag för utredning och rehabilitering
- 2014
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In: Läkartidningen. - Stockholm : Sveriges läkarförbund. - 0023-7205 .- 1652-7518. ; 111:49-50, s. 2230-2234
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Journal article (peer-reviewed)abstract
- After severe acquired brain injury some patients develop a prolonged disorder of consciousness (vegetative state or minimally conscious state), and as such cannot actively participate in neurorehabilitation. However, international opinion and recent research developments emphasize the need for involvement of rehabilitation medicine units in the care of these patients. The article presents recommendations for the care of adult patients with prolonged disorders of consciousness, which have been developed by a multidisciplinary working party, in order to promote good care, and identify areas for further improvements.
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| 7. |
- Markus, Tina, et al.
(author)
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beta-Adrenoceptor activation depresses brain inflammation and is neuroprotective in lipopolysaccharide-induced sensitization to oxygen-glucose deprivation in organotypic hippocampal slices
- 2010
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In: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 7
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Journal article (peer-reviewed)abstract
- Background: Inflammation acting in synergy with brain ischemia aggravates perinatal ischemic brain damage. The sensitizing effect of pro-inflammatory exposure prior to hypoxia is dependent on signaling by TNF-alpha through TNF receptor (TNFR) 1. Adrenoceptor (AR) activation is known to modulate the immune response and synaptic transmission. The possible protective effect of (alpha) over tilde and (beta) over tilde AR activation against neuronal damage caused by tissue ischemia and inflammation, acting in concert, was evaluated in murine hippocampal organotypic slices treated with lipopolysaccharide (LPS) and subsequently subjected to oxygen-glucose deprivation (OGD). Method: Hippocampal slices from mice were obtained at P6, and were grown in vitro for 9 days on nitrocellulose membranes. Slices were treated with beta 1(dobutamine)-, beta 2(terbutaline)-, alpha 1(phenylephrine)- and alpha 2(clonidine)-AR agonists (5 and 50 mu M, respectively) during LPS (1 mu g/mL, 24 h) -exposure followed by exposure to OGD (15 min) in a hypoxic chamber. Cell death in the slice CA1 region was assessed by propidium iodide staining of dead cells. Results: Exposure to LPS + OGD caused extensive cell death from 4 up to 48 h after reoxygenation. Co-incubation with beta 1-agonist (50 mu M) during LPS exposure before OGD conferred complete protection from cell death (P < 0.001) whereas the beta 2-agonist (50 mu M) was partially protective (p < 0.01). Phenylephrine was weakly protective while no protection was attained by clonidine. Exposure to both beta 1-and beta 2-agonist during LPS exposure decreased the levels of secreted TNF-alpha, IL-6 and monocyte chemoattractant protein-1 and prevented microglia activation in the slices. Dobutamine remained neuroprotective in slices exposed to pure OGD as well as in TNFR1(-/-) and TNFR2(-/-) slices exposed to LPS followed by OGD. Conclusions: Our data demonstrate that activation of both beta 1-and beta 2-receptors is neuroprotective and may offer mechanistic insights valuable for development of neuro-protective strategies in neonates.
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| 8. |
- Rundgren, Malin, et al.
(author)
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Serum neuron specific enolase - impact of storage and measuring method.
- 2014
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In: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 7:1
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Journal article (peer-reviewed)abstract
- Neuron specific enolase (NSE) is a recognized biomarker for assessment of neurological outcome after cardiac arrest, but its reliability has been questioned. Our aim was to investigate what influence storage of samples and choice of measuring methods may have on levels of NSE in peripheral blood.
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| 9. |
- Westhall, Erik, et al.
(author)
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Electroencephalography (EEG) for neurological prognostication after cardiac arrest and targeted temperature management; rationale and study design
- 2014
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In: BMC Neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 14
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Journal article (peer-reviewed)abstract
- Background: Electroencephalography (EEG) is widely used to assess neurological prognosis in patients who are comatose after cardiac arrest, but its value is limited by varying definitions of pathological patterns and by inter-rater variability. The American Clinical Neurophysiology Society (ACNS) has recently proposed a standardized EEG-terminology for critical care to address these limitations. In the Target Temperature Management (TTM) trial, a large international trial on temperature management after cardiac arrest, EEG-examinations were part of the prospective study design. The main objective of this study is to evaluate EEG-data from the TTM-trial and to identify malignant EEG-patterns reliably predicting a poor neurological outcome. Methods/Design: In the TTM-trial, 399 post cardiac arrest patients who remained comatose after rewarming underwent a routine EEG. The presence of clinical seizures, use of sedatives and antiepileptic drugs during the EEG-registration were prospectively documented. After the end of the trial, the EEGs were retrieved to form a central EEG-database. The EEG-data will be analysed using the ACNS EEG terminology. We designed an electronic case record form (eCRF). Four EEG-specialists from different countries, blinded to patient outcome, will independently classify the EEGs and report through the eCRF. We will describe the prognostic values of pre-specified EEG patterns to predict poor as well as good outcome. We hypothesise three patterns to always be associated with a poor outcome (suppressed background without discharges, suppressed background with continuous periodic discharges and burst-suppression). Inter- and intra-rater variability and whether sedation or level of temperature affects the prognostic values will also be analyzed. Discussion: A well-defined terminology for interpreting post cardiac arrest EEGs is critical for the use of EEG as a prognostic tool. The results of this study may help to validate the ACNS terminology for assessing post cardiac arrest EEGs and identify patterns that could reliably predict outcome.
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