| 1. |
- Poli, Sven, et al.
(författare)
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Penumbral Rescue by normobaric O?=?O administration in patients with ischemic stroke and target mismatch proFile (PROOF): Study protocol of a phase IIb trial
- 2024
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Ingår i: INTERNATIONAL JOURNAL OF STROKE. - 1747-4930 .- 1747-4949. ; 19:1, s. 120-126
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Oxygen is essential for cellular energy metabolism. Neurons are particularly vulnerable to hypoxia. Increasing oxygen supply shortly after stroke onset could preserve the ischemic penumbra until revascularization occurs.Aims: PROOF investigates the use of normobaric oxygen (NBO) therapy within 6 h of symptom onset/notice for brain-protective bridging until endovascular revascularization of acute intracranial anterior-circulation occlusion.Methods and design: Randomized (1:1), standard treatment-controlled, open-label, blinded endpoint, multicenter adaptive phase IIb trial.Study outcomes: Primary outcome is ischemic core growth (mL) from baseline to 24 h (intention-to-treat analysis). Secondary efficacy outcomes include change in NIHSS from baseline to 24 h, mRS at 90 days, cognitive and emotional function, and quality of life. Safety outcomes include mortality, intracranial hemorrhage, and respiratory failure. Exploratory analyses of imaging and blood biomarkers will be conducted.Sample size: Using an adaptive design with interim analysis at 80 patients per arm, up to 456 participants (228 per arm) would be needed for 80% power (one-sided alpha 0.05) to detect a mean reduction of ischemic core growth by 6.68 mL, assuming 21.4 mL standard deviation.Discussion: By enrolling endovascular thrombectomy candidates in an early time window, the trial replicates insights from preclinical studies in which NBO showed beneficial effects, namely early initiation of near 100% inspired oxygen during short temporary ischemia. Primary outcome assessment at 24 h on follow-up imaging reduces variability due to withdrawal of care and early clinical confounders such as delayed extubation and aspiration pneumonia.
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| 2. |
- Grand, Johannes, et al.
(författare)
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Arterial blood pressure during targeted temperature management after out-of-hospital cardiac arrest and association with brain injury and long-term cognitive function
- 2020
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Ingår i: European Heart Journal: Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 9:4_suppl, s. 122-130
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: During targeted temperature management after out-of-hospital cardiac arrest infusion of vasoactive drugs is often needed to ensure cerebral perfusion pressure. This study investigated mean arterial pressure after out-of-hospital cardiac arrest and the association with brain injury and long-term cognitive function. Methods: Post-hoc analysis of patients surviving at least 48 hours in the biobank substudy of the targeted temperature management trial with available blood pressure data. Patients were stratified in three groups according to mean arterial pressure during targeted temperature management (4–28 hours after admission; <70 mmHg, 70–80 mmHg, >80 mmHg). A biomarker of brain injury, neuron-specific enolase, was measured and impaired cognitive function was defined as a mini-mental state examination score below 27 in 6-month survivors. Results: Of the 657 patients included in the present analysis, 154 (23%) had mean arterial pressure less than 70 mmHg, 288 (44%) had mean arterial pressure between 70 and 80 mmHg and 215 (33%) had mean arterial pressure greater than 80 mmHg. There were no statistically significant differences in survival (P=0.35) or neuron-specific enolase levels (P=0.12) between the groups. The level of target temperature did not statistically significantly interact with mean arterial pressure regarding neuron-specific enolase (Pinteraction_MAP*TTM=0.58). In the subgroup of survivors with impaired cognitive function (n=132) (35%) mean arterial pressure during targeted temperature management was significantly higher (Pgroup=0.03). Conclusions: In a large cohort of comatose out-of-hospital cardiac arrest patients, low mean arterial pressure during targeted temperature management was not associated with higher neuron-specific enolase regardless of the level of target temperature (33°C or 36°C for 24 hours). In survivors with impaired cognitive function, mean arterial pressure during targeted temperature management was significantly higher.
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| 3. |
- Grand, Johannes, et al.
(författare)
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Cardiac output during targeted temperature management and renal function after out-of-hospital cardiac arrest
- 2019
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Ingår i: Journal of Critical Care. - : Elsevier BV. - 0883-9441. ; 54, s. 65-73
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: After resuscitation from out-of-hospital cardiac arrest (OHCA), renal injury and hemodynamic instability are common. We aimed to assess the association between low cardiac output during targeted temperature management (TTM) and acute kidney injury (AKI) after OHCA. Materials and methods: Single-center substudy of 171 patients included in the prospective, randomized TTM-trial. Hemodynamic evaluation was performed with serial measurements by pulmonary artery catheter. AKI was the primary endpoint and was defined according to the KDIGO-criteria. Results: Of 152 patients with available hemodynamic data, 49 (32%) had AKI and 21 (14%) had AKI with need for renal replacement therapy (RRT) in the first three days. During targeted temperature management, patients with AKI had higher heart rate (11 beats/min, pgroup < 0.0001), higher mean arterial pressure (MAP) (4 mmHg, pgroup = 0.001) and higher lactate (1 mmol/L, pgroup < 0.0001) compared to patients without AKI. However, there was no difference in cardiac index (pgroup = 0.25). In a multivariate logistic regression model, adjusting for potential confounders, MAP (p = .03), heart rate (p = .01) and lactate (p = .006), but not cardiac output, were independently associated with AKI. Conclusions: Blood pressure, heart rate and lactate, but not cardiac output, during 24 h of TTM were associated with AKI in comatose OHCA-patients.
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| 4. |
- Grand, Johannes, et al.
(författare)
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Mean arterial pressure during targeted temperature management and renal function after out-of-hospital cardiac arrest
- 2019
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Ingår i: Journal of Critical Care. - : Elsevier BV. - 0883-9441. ; 50, s. 234-241
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: This study investigates the association between mean arterial pressure (MAP) and renal function after out-of-hospital cardiac arrest (OHCA). Materials and methods: Post-hoc analysis of 851 comatose OHCA-patients surviving >48 h included in the targeted temperature management (TTM)-trial. Results: Patients were stratified by mean MAP during TTM in the following groups; <70 mmHg (22%), 70–80 mmHg (43%), and > 80 mmHg (35%). Median (interquartile range) eGFR (ml/min/1.73 m2) 48 h after OHCA was inversely associated with MAP-group (70 (47–102), 84 (56–113), 94 (61–124), p <.001, for the <70-group, 70–80-group and > 80-group respectively). After adjusting for potential confounders, in a mixed model including eGFR after 1, 2 and 3 days this association remained significant (pgroup_adjusted = 0.0002). Higher mean MAP was independently associated with lower odds of renal replacement therapy (odds ratioadjusted = 0.77 [95% confidence interval, 0.65–0.91] per 5 mmHg increase; p =.002]). Conclusions: Low mean MAP during TTM was independently associated with decreased renal function and need of renal replacement therapy in a large cohort of comatose OHCA-patients. Increasing MAP above the recommended 65 mmHg could potentially be renal-protective. This hypothesis should be investigated in prospective trials.
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| 5. |
- Grand, Johannes, et al.
(författare)
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Prevalence and Prognostic Implications of Bundle Branch Block in Comatose Survivors of Out-of-Hospital Cardiac Arrest
- 2016
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 118:8, s. 1194-1200
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Tidskriftsartikel (refereegranskat)abstract
- This study reports the prevalence and prognostic impact of right bundle branch block (RBBB) and left bundle branch block (LBBB) in the admission electrocardiogram (ECG) of comatose survivors of out-of-hospital cardiac arrest (OHCA). The present study is part of the predefined electrocardiographic substudy of the prospective randomized target temperature management trial, which found no benefit of targeting 33°C over 36°C in terms of outcome. Six-hundred eighty-two patients were included in the substudy. An admission ECG, which defined the present study population, was available in 602 patients (88%). These ECGs were stratified by the presence of LBBB, RBBB, or no-BBB (reference) on admission. End points were mortality and neurologic outcome 6 months after OHCA. RBBB was present in 79 patients (13%) and LBBB in 65 patients (11%), and the majority of BBBs (92%) had resolved 4 hours after admission. RBBB was associated with significantly higher 6 months mortality (RBBB: hazard ratio [HR]unadjusted 1.78, 95% confidence interval [CI] 1.30 to 2.43; LBBB: HRunadjusted 1.26, 95% CI 0.87 to 1.81), but this did not reach a level of significance in the adjusted model (HRadjusted 1.33, 95% CI 0.94 to 1.87). Similar findings were seen for neurologic outcome in the unadjusted and adjusted analyses. RBBB was further independently associated with higher odds of unfavorable neurologic outcome (RBBB: adjusted odds ratio 1.97, 95% CI 1.05 to 3.71). In conclusion, BBBs after OHCA were transient in most patients, and RBBB was directly associated with higher mortality and independently associated with higher odds of unfavorable neurologic outcome. RBBB is seemingly an early indicator of an unfavorable prognosis after OHCA.
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| 6. |
- Niemelä, Ville, et al.
(författare)
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Higher versus lower blood pressure targets after cardiac arrest : Systematic review with individual patient data meta-analysis
- 2023
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Ingår i: Resuscitation. - 0300-9572. ; 189
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Forskningsöversikt (refereegranskat)abstract
- Purpose: Guidelines recommend targeting mean arterial pressure (MAP) > 65 mmHg in patients after cardiac arrest (CA). Recent trials have studied the effects of targeting a higher MAP as compared to a lower MAP after CA. We performed a systematic review and individual patient data meta-analysis to investigate the effects of higher versus lower MAP targets on patient outcome. Method: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, LILACS, BIOSIS, CINAHL, Scopus, the Web of Science Core Collection, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry, Google Scholar and the Turning Research into Practice database to identify trials randomizing patients to higher (≥71 mmHg) or lower (≤70 mmHg) MAP targets after CA and resuscitation. We used the Cochrane Risk of Bias tool, version 2 (RoB 2) to assess for risk of bias. The primary outcomes were 180-day all-cause mortality and poor neurologic recovery defined by a modified Rankin score of 4–6 or a cerebral performance category score of 3–5. Results: Four eligible clinical trials were identified, randomizing a total of 1,087 patients. All the included trials were assessed as having a low risk for bias. The risk ratio (RR) with 95% confidence interval for 180-day all-cause mortality for a higher versus a lower MAP target was 1.08 (0.92–1.26) and for poor neurologic recovery 1.01 (0.86–1.19). Trial sequential analysis showed that a 25% or higher treatment effect, i.e., RR < 0.75, can be excluded. No difference in serious adverse events was found between the higher and lower MAP groups. Conclusions: Targeting a higher MAP compared to a lower MAP is unlikely to reduce mortality or improve neurologic recovery after CA. Only a large treatment effect above 25% (RR < 0.75) could be excluded, and future studies are needed to investigate if relevant but lower treatment effect exists. Targeting a higher MAP was not associated with any increase in adverse effects.
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| 7. |
- Skrifvars, Markus B., et al.
(författare)
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Protocol for an individual patient data meta-analysis on blood pressure targets after cardiac arrest
- 2022
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 66:7, s. 890-897
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Tidskriftsartikel (refereegranskat)abstract
- Background: Hypotension is common after cardiac arrest (CA), and current guidelines recommend using vasopressors to target mean arterial blood pressure (MAP) higher than 65 mmHg. Pilot trials have compared higher and lower MAP targets. We will review the evidence on whether higher MAP improves outcome after cardiac arrest. Methods: This systematic review and meta-analysis will be conducted based on a systematic search of relevant major medical databases from their inception onwards, including MEDLINE, Embase and the Cochrane Central Register of Controlled Trials (CENTRAL), as well as clinical trial registries. We will identify randomised controlled trials published in the English language that compare targeting a MAP higher than 65–70 mmHg in CA patients using vasopressors, inotropes and intravenous fluids. The data extraction will be performed separately by two authors (a third author will be involved in case of disagreement), followed by a bias assessment with the Cochrane Risk of Bias tool using an eight-step procedure for assessing if thresholds for clinical significance are crossed. The outcomes will be all-cause mortality, functional long-term outcomes and serious adverse events. We will contact the authors of the identified trials to request individual anonymised patient data to enable individual patient data meta-analysis, aggregate data meta-analyses, trial sequential analyses and multivariable regression, controlling for baseline characteristics. The certainty of the evidence will be assessed by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. We will register this systematic review with Prospero and aim to redo it when larger trials are published in the near future. Conclusions: This protocol defines the performance of a systematic review on whether a higher MAP after cardiac arrest improves patient outcome. Repeating this systematic review including more data likely will allow for more certainty regarding the effect of the intervention and possible sub-groups differences.
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| 8. |
- Stoll, Patrick Johannes, et al.
(författare)
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The global atmospheric energy transport analysed by a wavelength-based scale separation
- 2023
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Ingår i: Weather and Climate Dynamics. - : Copernicus Publications. - 2698-4024 .- 2698-4016. ; 4:1, s. 1-17
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Tidskriftsartikel (refereegranskat)abstract
- The atmosphere transports energy polewards by circulation cells and eddies. To the present day, there has been a knowledge gap regarding the preferred spatial scales and physical mechanisms of eddy energy transport. To fill the gap, we separate the meridional atmospheric energy transport in the ERA5 reanalysis by spatial scales and into quasi-stationary and transient flow patterns and latent and dry components.Baroclinic instability is the major instability mechanism in the transient synoptic scales and is responsible for forming cyclones, anticyclones, and small-scale Rossby waves. At the planetary scales, circulation patterns are often induced by other mechanisms such as flow interaction with orography and land–sea heating contrasts. However, a separation between circulation patterns at the synoptic and planetary scales has yet to be established. We find that both baroclinically induced and transient energy transport is predominantly associated with eddies at wavelengths between 2000 and 8000 km. The maxima in both types of transport occur at wavelengths around 5000 km, in good agreement with linear baroclinic theory. Since these results are independent of latitude, we adapt the scale separation of the energy transport to be based on the wavelength instead of the previously used wavenumber. We define the synoptic transport by the wavelength band between 2000 and 8000 km.We analyse the annual and seasonal mean in the energy transport components and their inter-annual variability. The scale-separated transport components are fairly similar in both hemispheres. Transport by synoptic waves is the largest contributor to extra-tropical energy and moisture transport, mainly of a transient character, and is influenced little by seasonality. In contrast, transport by planetary waves depends highly on the season and has two distinct characteristics. (1) In the extra-tropical winter, planetary waves are important due to a large transport of dry energy. This planetary transport features the largest inter-annual variability of all components and is mainly quasi-stationary in the Northern Hemisphere but transient in its southern counterpart. (2) In the sub-tropical summer, quasi-stationary planetary waves are the most important transport component, mainly due to moisture transport, presumably associated with monsoons. In contrast to transport by planetary and synoptic waves, only a negligible amount of energy is transported by mesoscale eddies (< 2000 km).
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