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result(s) for
"Grejs, Anders M"
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Neuropsychological outcome after cardiac arrest: results from a sub-study of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
by
Cronberg, Tobias
,
Grejs, Anders M.
,
Bro-Jeppesen, John
in
Analysis
,
Anxiety
,
Applied Psychology (including Clinical Psychology, Psychotherapy)
2023
Background
Cognitive impairment is common following out-of-hospital cardiac arrest (OHCA), but the nature of the impairment is poorly understood. Our objective was to describe cognitive impairment in OHCA survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.
Methods
This was a prospective case–control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. At approximately 7 months post-event, we administered an extensive neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes.
Results
Of 184 eligible OHCA survivors, 108 were included, with 92 MI controls enrolled. Amongst OHCA survivors, 29% performed
z
-score ≤ − 1 (at least borderline–mild impairment) in ≥ 2 cognitive domains, 14% performed
z
-score ≤ − 2 (major impairment) in ≥ 1 cognitive domain while 54% performed without impairment in any domain. Impairment was most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = − 0.37, 95% confidence intervals [− 0.61, − 0.12]), verbal (MD = − 0.34 [− 0.62, − 0.07]), and visual/constructive functions (MD = − 0.26 [− 0.47, − 0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, executive functions (MD = − 0.44 [− 0.82, − 0.06]) were also worse following OHCA. Diabetes, symptoms of anxiety, depression, and fatigue were significantly associated with worse cognitive performance.
Conclusions
In our study population, cognitive impairment was generally mild following OHCA. OHCA survivors performed worse than MI controls in 3 of 6 domains. These results support current guidelines that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.
Trial registration
ClinicalTrials.gov, NCT03543371. Registered 1 June 2018.
Journal Article
Intravascular versus surface cooling for targeted temperature management after out-of-hospital cardiac arrest: an analysis of the TTH48 trial
by
Creteur, Jacques
,
Kirkegaard, Hans
,
Taccone, Fabio Silvio
in
Cardiac arrest
,
Care and treatment
,
Comparative analysis
2019
Background
The aim of this study was to explore the performance and outcomes for intravascular (IC) versus surface cooling devices (SFC) for targeted temperature management (TTM) after out-of-hospital cardiac arrest.
Methods
A retrospective analysis of data from the Time-differentiated Therapeutic Hypothermia (TTH48) trial (NCT01689077), which compared whether TTM at 33 °C for 48 h results in better neurologic outcomes compared with standard 24-h duration. Devices were assessed for the speed of cooling and rewarming rates. Precision was assessed by measuring temperature variability (TV), i.e., the standard deviation (SD) of all temperature measurements in the cooling phase. Main outcomes were overall mortality and poor neurological outcome, including death, severe disability, or vegetative status.
Results
A total of 352 patients had available data and were included in the analysis; of those, 218 (62%) were managed with IC. A total of 114/218 (53%) patients with IC and 61/134 (43%) with SFC were cooled for 48 h (
p
= 0.22). Time to target temperature (≤ 34 °C) was significantly shorter for patients treated with endovascular devices (2.2 [1.1–4.0] vs. 4.2 [2.7–6.0] h,
p
< 0.001), but temperature was also lower on admission (35.0 [34.2–35.6] vs. 35.3 [34.5–35.8]°C;
p
= 0.02) and cooling rate was similar (0.4 [0.2–0.8] vs. 0.4 [0.2–0.6]°C/h;
p
= 0.14) when compared to SFC. Temperature variability was significantly lower in the endovascular device group when compared with SFC methods (0.6 [0.4–0.9] vs. 0.7 [0.5–1.0]°C;
p
= 0.007), as was rewarming rate (0.31 [0.22–0.44] vs. 0.37 [0.29–0.49]°C/hour;
p
= 0.02). There was no statistically significant difference in mortality (endovascular 65/218, 29% vs. others 43/134, 32%;
p
= 0.72) or poor neurological outcome (endovascular 69/218, 32% vs. others 51/134, 38%;
p
= 0.24) between type of devices.
Conclusions
Endovascular cooling devices were more precise than SFC methods in patients cooled at 33 °C after out-of-hospital cardiac arrest. Main outcomes were similar with regard to the cooling methods.
Journal Article
Speed of cooling after cardiac arrest in relation to the intervention effect: a sub-study from the TTM2-trial
by
Young, Paul J.
,
Taccone, Fabio Silvio
,
Grejs, Anders M.
in
Artificial respiration
,
Body temperature
,
Cardiac arrest
2022
Background
Targeted temperature management (TTM) is recommended following cardiac arrest; however, time to target temperature varies in clinical practice. We hypothesised the effects of a target temperature of 33 °C when compared to normothermia would differ based on average time to hypothermia and those patients achieving hypothermia fastest would have more favorable outcomes.
Methods
In this post-hoc analysis of the TTM-2 trial, patients after out of hospital cardiac arrest were randomized to targeted hypothermia (33 °C), followed by controlled re-warming, or normothermia with early treatment of fever (body temperature, ≥ 37.8 °C). The average temperature at 4 h (240 min) after return of spontaneous circulation (ROSC) was calculated for participating sites. Primary outcome was death from any cause at 6 months. Secondary outcome was poor functional outcome at 6 months (score of 4–6 on modified Rankin scale).
Results
A total of 1592 participants were evaluated for the primary outcome. We found no evidence of heterogeneity of intervention effect based on the average time to target temperature on mortality (
p
= 0.17). Of patients allocated to hypothermia at the fastest sites, 71 of 145 (49%) had died compared to 68 of 148 (46%) of the normothermia group (relative risk with hypothermia, 1.07; 95% confidence interval 0.84–1.36). Poor functional outcome was reported in 74/144 (51%) patients in the hypothermia group, and 75/147 (51%) patients in the normothermia group (relative risk with hypothermia 1.01 (95% CI 0.80–1.26).
Conclusions
Using a hospital’s average time to hypothermia did not significantly alter the effect of TTM of 33 °C compared to normothermia and early treatment of fever.
Journal Article
Neuropsychological outcome after cardiac arrest: a prospective case control sub-study of the Targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest trial (TTM2)
by
Cronberg, Tobias
,
Grejs, Anders M.
,
Keeble, Thomas
in
Anestesi och intensivvård
,
Anesthesiology and Intensive Care
,
Angiology
2020
Background
This study is designed to provide detailed knowledge on cognitive impairment after out-of-hospital cardiac arrest (OHCA) and its relation to associated factors, and to validate the neurocognitive screening of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial), assessing effectiveness of targeted temperature management after OHCA.
Methods
This longitudinal multi-center clinical study is a sub-study of the TTM2-trial, in which a comprehensive neuropsychological examination is performed in addition to the main TTM2-trial neurocognitive screening. Approximately 7 and 24 months after OHCA, survivors at selected study sites are invited to a standardized assessment, including performance-based tests of cognition and questionnaires of emotional problems, fatigue, executive function and insomnia. At 1:1 ratio, a matched control group from a cohort of acute myocardial infarction (MI) patients is recruited to perform the same assessment. We aim to include 100 patients per group. Potential differences between the OHCA patients and the MI controls at 7 and 24 months will be analyzed with a linear regression, using composite
z
-scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions) as primary outcome measures. Results from OHCA survivors on the main TTM2-trial neurocognitive screening battery will be compared with neuropsychological test results at 7 months, using sensitivity and specificity analyses.
Discussion
In this study we collect detailed information on cognitive impairment after OHCA and compare this to a control group of patients with acute MI. The validation of the TTM2 neurocognitive screening battery could justify its inclusion in routine follow-up. Our results may have a potential to impact on the design of future follow-up strategies and interventions after OHCA.
Trial registration
ClinicalTrials.gov,
NCT03543371
. Registered 1 June 2018
Journal Article
Managing Known Difficult Airways in Obstetric Patients Using a Flexible Bronchoscope and IRRIS: A Case-Illustrated Guide for Nonexpert Anesthesiologists, without Surgical Backup
by
Herzog, Jan
,
Grejs, Anders M.
,
Kristensen, Michael S.
in
Airway management
,
Bupivacaine
,
Case Report
2021
Pregnancy is associated with anatomical and physiological changes leading to potential difficult airway management. Some pregnant women have known difficult airways and cannot be intubated even with a hyperangulated videolaryngoscope. If neuraxial techniques are also impossible, awake tracheal intubation with a flexible bronchoscope may be one of the few available options to avoid more invasive techniques. The Infrared Red Intubation System (IRRIS) may help nonexpert anesthesiologists in such situations and may enhance the chance of successful intubation increasing safety for the mother and the fetus, especially in hospitals without the ear, nose, and throat surgical backup.
Journal Article
Intravascular vs. surface cooling in out-of-hospital cardiac arrest patients receiving hypothermia after hospital arrival: a post hoc analysis of the TTM2 trial
2025
Purpose
To compare the performance of targeted temperature management (TTM) at 33 °C using intravascular (IC) vs. surface-cooling (SFC) devices after out-of-hospital cardiac arrest (OHCA).
Methods
A post hoc analysis including OHCA patients randomized to hypothermia in the TTM2-trial (NCT02908308) comparing hypothermia with normothermia. The main outcome was cooling performance, defined as the proportion of patients reaching target temperature < 33.5 °C within 4 h, time outside temperature ranges during maintenance, rewarming rate and post-TTM fever. Exploratory outcomes included survival and good functional outcome, defined as modified Rankin Scale (mRS) scores of 0–3 at 6 months, analyzed using Inverse Probability Treatment Weighting (IPTW).
Results
Among 930 patients randomized to hypothermia, 876 were treated with a cooling device and included in this study. Of those, 27.3% received IC devices, while 72.7% received SFC devices. The proportion reaching target temperature within 4 h was higher with IC (IC: 69.6% vs. SFC: 49.2%;
p
< 0.001). Temperature outside ranges during the cooling period and post-TTM fever were lower with IC compared to SFC (17.2% vs. 39.6%;
p
< 0.001 and 0% vs. 6.3%;
p
< 0.001, respectively). In the exploratory IPTW analysis, 6-month survival rates were 55.2% in the IC group and 50.2% in the SFC group (OR 1.22, 95% CI 0.89–1.68) and survival with good functional outcome at 6 months was 51.1% patients in the IC group and 44.9% in the SFC (OR 1.28, 95% CI 0.93–1.77).
Conclusions
Among OHCA patients randomized to hypothermia in the TTM2 study, intravascular cooling, compared with surface cooling, was associated with better cooling performance.
Journal Article
Dysnatremia at ICU admission and functional outcome of cardiac arrest: insights from four randomised controlled trials
2023
Purpose
To evaluate the potential association between early dysnatremia and 6-month functional outcome after cardiac arrest.
Methods
We pooled data from four randomised clinical trials in post-cardiac-arrest patients admitted to the ICU with coma after stable return of spontaneous circulation (ROSC). Admission natremia was categorised as normal (135–145 mmol/L), low, or high. We analysed associations between natremia category and Cerebral Performance Category (CPC) 1 or 2 at 6 months, with and without adjustment on the modified Cardiac Arrest Hospital Prognosis Score (mCAHP).
Results
We included 1163 patients (581 from HYPERION, 352 from TTH48, 120 from COMACARE, and 110 from Xe-HYPOTHECA) with a mean age of 63 ± 13 years and a predominance of males (72.5%). A cardiac cause was identified in 63.6% of cases. Median time from collapse to ROSC was 20 [15–29] minutes. Overall, mean natremia on ICU admission was 137.5 ± 4.7 mmol/L; 211 (18.6%) and 31 (2.7%) patients had hyponatremia and hypernatremia, respectively. By univariate analysis, CPC 1 or 2 at 6 months was significantly less common in the group with hyponatremia (50/211 [24%] vs. 363/893 [41%];
P
= 0.001); the mCAHP-adjusted odds ratio was 0.45 (95%CI 0.26–0.79,
p
= 0.005). The number of patients with hypernatremia was too small for a meaningful multivariable analysis.
Conclusions
Early hyponatremia was common in patients with ROSC after cardiac arrest and was associated with a poorer 6-month functional outcome. The mechanisms underlying this association remain to be elucidated in order to determine whether interventions targeting hyponatremia are worth investigating.
Registration
ClinicalTrial.gov, NCT01994772, November 2013, 21.
Journal Article
Acute Awake Fiberoptic Intubation in the ICU in a Patient with Limited Mouth Opening and Hypoxemic Acute Respiratory Failure
by
Grejs, Anders M.
,
Hauritz, Rasmus Wulff
,
Hannig, Kjartan Eskjaer
in
Acute respiratory distress syndrome
,
Airway management
,
Anesthesia
2019
The incidence and survival of patients with head-and-neck cancer have been on the increase for decades. Following surgery or radiation therapy, complications such as difficult airways may evolve. These difficult airways may be unique and not manageable with conventional intubation methods as well as video laryngoscopes. Acute awake fiberoptic intubation may be a feasible option also for urgent emergency airway management of known difficult airways. The “cannot intubate–cannot oxygenate” (CI–CO) situation has to be avoided at all costs, since emergency cricothyrotomy has a fail ratio of more than 50% when performed by an anesthesiologist.
Journal Article
1 Neuropsychological Outcome After Cardiac Arrest: Results from a Sub-study of the Targeted Hypothermia Versus Targeted Normothermia After Out-of-hospital Cardiac Arrest (TTM2) Trial
by
Cronberg, Tobias
,
Grejs, Anders M.
,
Bro-Jeppesen, John
in
Anoxia/Hypoxia
,
Anxiety
,
Cardiac arrest
2023
Objective:To describe cognitive impairment in out-of-hospital cardiac arrest (OHCA) survivors, with the hypothesis that OHCA survivors would perform significantly worse on neuropsychological tests of cognition than controls with acute myocardial infarction (MI). Another aim was to investigate the relationship between cognitive performance and the associated factors of emotional problems, fatigue, insomnia, and cardiovascular risk factors following OHCA.Participants and Methods:This was a prospective case control sub-study of The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Eight of 61 TTM2-sites in Sweden, Denmark, and the United Kingdom included adults with OHCA of presumed cardiac or unknown cause. A matched non-arrest control group with acute MI was recruited. We administered an extensive neuropsychological assessment at approximately 7 months post-cardiac event, including a neuropsychological test battery and questionnaires on anxiety, depression, fatigue, and insomnia, and collected information on the cardiovascular risk factors hypertension and diabetes. Z-scores of individual tests were converted to neuropsychological composite scores per cognitive domain (verbal, visual/constructive, working memory, episodic memory, processing speed, executive functions). Between-group differences on the neuropsychological composite scores were investigated with linear regression. Associations between anxiety, depression, fatigue, insomnia, hypertension, diabetes, and the neuropsychological composite scores among OHCA survivors were calculated with Spearman’s rho.Results:Of 184 eligible OHCA survivors, 108 were included (mean age = 62, 88% male), with 92 MI controls enrolled (mean age = 64, 89% male). Amongst OHCA survivors, 29% performed z <-1 indicating at least borderline-mild impairment in >2 cognitive domains, and 14% performed z <-2 exhibiting major impairment in >1 cognitive domain. OHCA survivors performed significantly worse than MI controls in episodic memory (mean difference, MD = -0.37, 95% confidence intervals [-0.61, -0.12]), verbal (MD = -0.34 [-0.62, -0.07]), and visual/constructive functions (MD = -0.26 [-0.47, -0.04]) on linear regressions adjusted for educational attainment and sex. When additionally adjusting for anxiety, depression, fatigue, insomnia, hypertension, and diabetes, processing speed (MD = -0.41 [-0.74, -0.09]) and executive functions (MD = -0.69 [-1.13, -0.24]) were also worse following OHCA. Depressive symptoms were associated with worse executive functions (rs = -0.37, p <0.001) and worse processing speed (rs = -0.27, p = 0.01) post-OHCA. Anxiety symptoms (rs = -0.21, p = 0.01) and general fatigue (rs = -0.24, p = 0.01) were associated with worse executive functions. Diabetes was associated with worse processing speed (rs = -0.20, p = 0.03), visual/constructive (rs = -0.29, p <0.001) and executive functions (rs = -0.25, p = 0.02), while hypertension and insomnia were not significantly associated with neuropsychological test performance.Conclusions:Cognitive impairment is generally mild following OHCA, but most pronounced in episodic memory, executive functions, and processing speed. OHCA survivors performed worse than MI controls. We suggest that a post-OHCA follow-up service should screen for cognitive impairment, emotional problems, and fatigue.
Journal Article
Severe or critical hypotension during post cardiac arrest care is associated with factors available on admission - a post hoc analysis of the TTH48 trial
by
Kirkegaard, Hans
,
Taccone, Fabio Silvio
,
Storm, Christian
in
Ambulance services
,
Cardiac arrest
,
Comorbidity
2021
We explored whether severe or critical hypotension can be predicted, based on patient and resuscitation characteristics in out-of-hospital cardiac arrest (OHCA) patients. We also explored the association of hypotension with mortality and neurological outcome.
We conducted a post hoc analysis of the TTH48 study (NCT01689077), where 355 out-of-hospital cardiac arrest (OHCA) patients were randomized to targeted temperature management (TTM) treatment at 33 °C for either 24 or 48 h. We recorded hypotension, according to four severity categories, within four days from admission. We used multivariable logistic regression analysis to test association of admission data with severe or critical hypotension.
Diabetes mellitus (OR 3.715, 95% CI 1.180–11.692), longer ROSC delay (OR 1.064, 95% CI 1.022–1.108), admission MAP (OR 0.960, 95% CI 0.929–0.991) and non-shockable rhythm (OR 5.307, 95% CI 1.604–17.557) were associated with severe or critical hypotension. Severe or critical hypotension was associated with increased mortality and poor neurological outcome at 6 months.
Diabetes, non-shockable rhythm, longer delay to ROSC and lower admission MAP were predictors of severe or critical hypotension. Severe or critical hypotension was associated with poor outcome.
•Diabetes increases the risk for hypotension during the first four days of post-cardiac arrest care in the ICU.•Even mild hypotension during the post-cardiac arrest care is associated with poor outcome.•Duration of Targeted Temperature Management is not linked to increased incidence of hypotension during post-cardiac arrest care.
Journal Article