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| 2. |
- Glassford, Neil J., et al.
(författare)
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The nature and discriminatory value of urinary neutrophil gelatinase-associated lipocalin in critically ill patients at risk of acute kidney injury
- 2013
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 39:10, s. 1714-1724
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Tidskriftsartikel (refereegranskat)abstract
- Different molecular forms of urinary neutrophil gelatinase-associated lipocalin (NGAL) have recently been discovered. We aimed to explore the nature, source and discriminatory value of urinary NGAL in intensive care unit (ICU) patients. We simultaneously measured plasma NGAL (pNGAL), urinary NGAL (uNGAL), and estimated monomeric and homodimeric uNGAL contribution using Western blotting-validated enzyme-linked immunosorbent assays [uNGAL(E1) and uNGAL(E2)] and their calculated ratio in 102 patients with the systemic inflammatory response syndrome and oliguria, and/or a creatinine rise of > 25 mu mol/L. Bland-Altman analysis demonstrated that, despite correlating well (r = 0.988), uNGAL and uNGAL(E1) were clinically distinct, lacking both accuracy and precision (bias: 266.23; 95 % CI 82.03-450.44 ng/mg creatinine; limits of agreement: -1,573.86 to 2,106.32 ng/mg creatinine). At best, urinary forms of NGAL are fair (area under the receiver operating characteristic [AUROC] a parts per thousand currency sign0.799) predictors of renal or patient outcome; most perform significantly worse. The 44 patients with a primarily monomeric source of uNGAL had higher pNGAL (118.5 ng/ml vs. 72.5 ng/ml; p < 0.001), remaining significant following Bonferroni correction. uNGAL is not a useful predictor of outcome in this ICU population. uNGAL patterns may predict distinct clinical phenotypes. The nature and source of uNGAL are complex and challenge the utility of NGAL as a uniform biomarker.
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| 3. |
- Holgersson, Johan, et al.
(författare)
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Hypothermic versus Normothermic Temperature Control after Cardiac Arrest
- 2022
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Ingår i: NEJM Evidence. - 2766-5526. ; 1:11, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDThe evidence for temperature control for comatose survivors of cardiac arrest is inconclusive. Controversy exists as to whether the effects of hypothermia differ per the circumstances of the cardiac arrest or patient characteristics.METHODSAn individual patient data meta-analysis of the Targeted Temperature Management at 33°C versus 36°C after Cardiac Arrest (TTM) and Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trials was conducted. The intervention was hypothermia at 33°C and the comparator was normothermia. The primary outcome was all-cause mortality at 6 months. Secondary outcomes included poor functional outcome (modified Rankin scale score of 4 to 6) at 6 months. Predefined subgroups based on the design variables in the original trials were tested for interaction with the intervention as follows: age (older or younger than the median), sex (female or male), initial cardiac rhythm (shockable or nonshockable), time to return of spontaneous circulation (above or below the median), and circulatory shock on admission (presence or absence).RESULTSThe primary analyses included 2800 patients, with 1403 assigned to hypothermia and 1397 to normothermia. Death occurred for 691 of 1398 participants (49.4%) in the hypothermia group and 666 of 1391 participants (47.9%) in the normothermia group (relative risk with hypothermia, 1.03; 95% confidence interval [CI], 0.96 to 1.11; P=0.41). A poor functional outcome occurred for 733 of 1350 participants (54.3%) in the hypothermia group and 718 of 1330 participants (54.0%) in the normothermia group (relative risk with hypothermia, 1.01; 95% CI, 0.94 to 1.08; P=0.88). Outcomes were consistent in the predefined subgroups.CONCLUSIONSHypothermia at 33°C did not decrease 6-month mortality compared with normothermia after out-of-hospital cardiac arrest. (Funded by Vetenskapsrådet; ClinicalTrials.gov numbers NCT02908308 and NCT01020916.)
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| 4. |
- Lilja, Gisela, et al.
(författare)
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Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
- 2020
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Aims: The TTM2-trial is a multi-centre randomised clinical trial where targeted temperature management (TTM) at 33 °C will be compared with normothermia and early treatment of fever (≥37.8 °C) after Out-of-Hospital Cardiac Arrest (OHCA). This paper presents the design and rationale of the TTM2-trial follow-up, where information on secondary and exploratory outcomes will be collected. We also present the explorative outcome analyses which will focus on neurocognitive function and societal participation in OHCA-survivors. Methods: Blinded outcome-assessors will perform follow-up at 30-days after the OHCA with a telephone interview, including the modified Rankin Scale (mRS) and the Glasgow Outcome Scale Extended (GOSE). Face-to-face meetings will be performed at 6 and 24-months, and include reports on outcome from several sources of information: clinician-reported: mRS, GOSE; patient-reported: EuroQol-5 Dimensions-5 Level responses version (EQ-5D-5L), Life satisfaction, Two Simple Questions; observer-reported: Informant Questionnaire on Cognitive Decline in the Elderly-Cardiac Arrest version (IQCODE-CA) and neurocognitive performance measures: Montreal Cognitive Assessment, (MoCA), Symbol Digit Modalities Test (SDMT). Exploratory analyses will be performed with an emphasis on brain injury in the survivors, where the two intervention groups will be compared for potential differences in neuro-cognitive function (MoCA, SDMT) and societal participation (GOSE). Strategies to increase inter-rater reliability and decrease missing data are described. Discussion: The TTM2-trial follow-up is a pragmatic yet detailed pre-planned and standardised assessment of patient's outcome designed to ensure data-quality, decrease missing data and provide optimal conditions to investigate clinically relevant effects of TTM, including OHCA-survivors’ neurocognitive function and societal participation.
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| 5. |
- Lipcsey, Miklos, et al.
(författare)
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Near-infrared spectroscopy of the thenar eminence : comparison of dynamic testing protocols
- 2012
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Ingår i: Critical Care and Resuscitation. - 1441-2772. ; 14:2, s. 142-147
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Tidskriftsartikel (refereegranskat)abstract
- Background: Near-infrared spectroscopy of the thenar eminence (NIRSth) is a non-invasive bedside method for assessing tissue oxygenation. The vascular occlusion test (VOT) with a pressure cuff can be used to provide a dynamic assessment of the tissue oxygenation response to ischaemia. VOT has been applied to assess the microcirculation by NIRSth in critically ill patients. The optimal mode of performing such VOT, however, remains controversial. Design, participants and setting: Prospective observational study among a cohort of 11 healthy volunteers in a tertiary intensive care department. Intervention: Measurement of NIRS-derived parameters using 1-, 2- and 3-minute VOTs or VOT to 40% tissue oxygen saturation (StO(2)). Main outcome measure: Changes in StO(2) and tissue haemoglobin index (THI) over time, and relative change from baseline for StO(2) and THI. Results: Mean baseline StO(2) was 80% (SD, 5%) and mean THI was 13.7 (SD, 1.9). The lowest StO(2) at the end of the VOT was 39% (SD, 13%) and 39% (SD, 2%) in the 3-minute and the 40% StO(2) VOTs, respectively. The duration of the 40% StO(2) VOT ranged from 1:35 to 8:21 minutes (median, 3:29 min). There was a difference between the StO(2) curves for the 3-minute and 40% StO(2) VOT (P = 0.005) but not the THI curves. Reported pain score was a median of 3.5 (IQR, 2.5-5.5) and 4 (IQR 2-4) for the 3-minute and 40% StO(2) VOTs, respectively. Conclusions: The 3-minute VOT and the 40% StO(2) appear equivalent. However, the 3-minute VOT carries a degree of decreased patient discomfort and shorter overall duration of execution.
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| 6. |
- Moseby-Knappe, Marion, et al.
(författare)
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Biomarkers of brain injury after cardiac arrest; a statistical analysis plan from the TTM2 trial biobank investigators
- 2022
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Ingår i: Resuscitation Plus. - : Elsevier. - 2666-5204. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several biochemical markers in blood correlate with the magnitude of brain injury and may be used to predict neurological outcome after cardiac arrest. We present a protocol for the evaluation of prognostic accuracy of brain injury markers after cardiac arrest. The aim is to define the best predictive marker and to establish clinically useful cut-off levels for routine implementation. Methods: Prospective international multicenter trial within the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial in collaboration with Roche Diagnostics International AG. Samples were collected 0, 24, 48, and 72 hours after randomisation (serum) and 0 and 48 hours after randomisation (plasma), and pre-analytically processed at each site before storage in a central biobank. Routine markers neuron-specific enolase (NSE) and S100B, and neurofilament light, total-tau and glial fibrillary acidic protein will be batch analysed using novel Elecsys (R) electrochemiluminescence immunoassays on a Cobas e601 instrument. Results: Statistical analysis will be reported according to the Standards for Reporting Diagnostic accuracy studies (STARD) and will include comparisons for prediction of good versus poor functional outcome at six months post-arrest, by modified Rankin Scale (0-3 vs. 4-6), using logistic regression models and receiver operating characteristics curves, evaluation of mortality at six months according to biomarker levels and establishment of cut-off values for prediction of poor neurological outcome at 95-100% specificities. Conclusions: This prospective trial may establish a standard methodology and clinically appropriate cut-off levels for the optimal biomarker of brain injury which predicts poor neurological outcome after cardiac arrest.
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| 7. |
- Nichol, Alistair, et al.
(författare)
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Protocol summary and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial
- 2021
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Ingår i: Critical Care and Resuscitation. - 1441-2772. ; 23:4, s. 374-385
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted therapeutic mild hypercapnia may attenuate brain injury in comatose adults resuscitated from out-of-hospital cardiac arrest. Objective: To describe the study protocol and statistical analysis plan for the Targeted Therapeutic Mild Hypercapnia after Resuscitated Cardiac Arrest (TAME) trial. Design, setting, participants and interventions: TAME is a phase 3, multicentre, parallel-group, participant-and outcome assessor-blinded randomised controlled trial that will be conducted in intensive care units in Australia, Canada, Ireland, Saudi Arabia, New Zealand, Scandinavia, Singapore, Central and Western Europe, and the United Kingdom. A total of 1700 comatose adults resuscitated from out-of-hospital cardiac arrest will be randomly assigned to 24 hours of targeted therapeutic mild hypercapnia (arterial carbon dioxide tension 50–55 mmHg) or targeted normocapnia (arterial carbon dioxide tension 35–45 mmHg) in a 1:1 ratio. TAME recruitment began in March 2018 and is expected to be complete in September 2021. Main outcome measures: The primary outcome measure is the proportion of participants with a favourable functional outcome at 6 months. Functional outcomes will be assessed using the Glasgow Outcome Scale-Extended (GOSE); this scale ranges from 1 to 8, with a higher value indicating a better outcome. We will define participants with a GOSE of 5 to 8 as having a favourable functional outcome. Secondary outcomes include 6-month mortality, cognitive function and quality of life. All analyses will be conducted on an intention-to-treat basis. Results and conclusions: TAME will compare the effect of targeted therapeutic mild hypercapnia versus targeted normocapnia on functional outcomes in adults resuscitated from out-of-hospital cardiac arrest who are admitted to an intensive care unit. Trial registration: Australian and New Zealand Clinical Trials Registry (ACTRN12617000036314p) and ClinicalTrials.gov (NCT03114033).
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| 9. |
- Robba, Chiara, et al.
(författare)
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Oxygen targets and 6-month outcome after out of hospital cardiac arrest : a pre-planned sub-analysis of the targeted hypothermia versus targeted normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods: Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 < 60 mmHg and severe hyperoxemia as PaO2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results: 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions: In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.
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| 10. |
- Schneider, Antoine G, et al.
(författare)
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Arterial carbon dioxide tension and outcome in patients admitted to the intensive care unit after cardiac arrest
- 2013
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 84:7, s. 927-934
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundArterial carbon dioxide tension (PaCO2) affects neuronal function and cerebral blood flow. However, its association with outcome in patients admitted to intensive care unit (ICU) after cardiac arrest (CA) has not been evaluated.Methods and resultsObservational cohort study using data from the Australian New Zealand (ANZ) Intensive Care Society Adult-Patient-Database (ANZICS-APD). Outcomes analyses were adjusted for illness severity, co-morbidities, hypothermia, treatment limitations, age, year of admission, glucose, source of admission, PaO2 and propensity score.We studied 16,542 consecutive patients admitted to 125 ANZ ICUs after CA between 2000 and 2011. Using the APD-PaCO2 (obtained within 24 h of ICU admission), 3010 (18.2%) were classified into the hypo- (PaCO2 < 35 mmHg), 6705 (40.5%) into the normo- (35–45 mmHg) and 6827 (41.3%) into the hypercapnia (>45 mmHg) group. The hypocapnia group, compared with the normocapnia group, had a trend toward higher in-hospital mortality (OR 1.12 [95% CI 1.00–1.24, p = 0.04]), lower rate of discharge home (OR 0.81 [0.70–0.94, p < 0.01]) and higher likelihood of fulfilling composite adverse outcome of death and no discharge home (OR 1.23 [1.10–1.37, p < 0.001]). In contrast, the hypercapnia group had similar in-hospital mortality (OR 1.06 [0.97–1.15, p = 0.19]) but higher rate of discharge home among survivors (OR 1.16 [1.03–1.32, p = 0.01]) and similar likelihood of fulfilling the composite outcome (OR 0.97 [0.89–1.06, p = 0.52]). Cox-proportional hazards modelling supported these findings.ConclusionsHypo- and hypercapnia are common after ICU admission post-CA. Compared with normocapnia, hypocapnia was independently associated with worse clinical outcomes and hypercapnia a greater likelihood of discharge home among survivors.
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