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1.
  • Dankiewicz, Josef, et al. (författare)
  • Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
  • 2021
  • Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
  • Tidskriftsartikel (refereegranskat)abstract
    • Hypothermia or Normothermia after Cardiac Arrest This trial randomly assigned patients with coma after out-of-hospital cardiac arrest to undergo targeted hypothermia at 33 degrees C or normothermia with treatment of fever. At 6 months, there were no significant between-group differences regarding death or functional outcomes. Background Targeted temperature management is recommended for patients after cardiac arrest, but the supporting evidence is of low certainty. Methods In an open-label trial with blinded assessment of outcomes, we randomly assigned 1900 adults with coma who had had an out-of-hospital cardiac arrest of presumed cardiac or unknown cause to undergo targeted hypothermia at 33 degrees C, followed by controlled rewarming, or targeted normothermia with early treatment of fever (body temperature, >= 37.8 degrees C). The primary outcome was death from any cause at 6 months. Secondary outcomes included functional outcome at 6 months as assessed with the modified Rankin scale. Prespecified subgroups were defined according to sex, age, initial cardiac rhythm, time to return of spontaneous circulation, and presence or absence of shock on admission. Prespecified adverse events were pneumonia, sepsis, bleeding, arrhythmia resulting in hemodynamic compromise, and skin complications related to the temperature management device. Results A total of 1850 patients were evaluated for the primary outcome. At 6 months, 465 of 925 patients (50%) in the hypothermia group had died, as compared with 446 of 925 (48%) in the normothermia group (relative risk with hypothermia, 1.04; 95% confidence interval [CI], 0.94 to 1.14; P=0.37). Of the 1747 patients in whom the functional outcome was assessed, 488 of 881 (55%) in the hypothermia group had moderately severe disability or worse (modified Rankin scale score >= 4), as compared with 479 of 866 (55%) in the normothermia group (relative risk with hypothermia, 1.00; 95% CI, 0.92 to 1.09). Outcomes were consistent in the prespecified subgroups. Arrhythmia resulting in hemodynamic compromise was more common in the hypothermia group than in the normothermia group (24% vs. 17%, P<0.001). The incidence of other adverse events did not differ significantly between the two groups. Conclusions In patients with coma after out-of-hospital cardiac arrest, targeted hypothermia did not lead to a lower incidence of death by 6 months than targeted normothermia. (Funded by the Swedish Research Council and others; TTM2 ClinicalTrials.gov number, .)
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2.
  • Düring, J., et al. (författare)
  • Lactate, lactate clearance and outcome after cardiac arrest : A post-hoc analysis of the TTM-Trial
  • 2018
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 62:10, s. 1436-1442
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Admission lactate and lactate clearance are implemented for risk stratification in sepsis and trauma. In out-of-hospital cardiac arrest, results regarding outcome and lactate are conflicting. Methods: This is a post-hoc analysis of the Target Temperature Management trial in which 950 unconscious patents after out-of-hospital cardiac arrest were randomized to a temperature intervention of 33°C or 36°C. Serial lactate samples during the first 36 hours were collected. Admission lactate, 12-hour lactate, and the clearance of lactate within 12 hours after admission were analyzed and the association with 30-day mortality assessed. Results: Samples from 877 patients were analyzed. In univariate logistic regression analysis, the odds ratio for death by day 30 for each mmol/L was 1.12 (1.08-1.16) for admission lactate, P <.01, 1.21 (1.12-1.31) for 12-hour lactate, P <.01, and 1.003 (1.00-1.01) for each percentage point increase in 12-hour lactate clearance, P =.03. Only admission lactate and 12-hour lactate levels remained significant after adjusting for known predictors of outcome. The area under the receiver operating characteristic curve was 0.65 (0.61-0.69), P <.001, 0.61 (0.57-0.65), P <.001, and 0.53 (0.49-0.57), P =.15 for admission lactate, 12-hour lactate, and 12-hour lactate clearance, respectively. Conclusions: Admission lactate and 12-hour lactate values were independently associated with 30-day mortality after out-of-hospital cardiac arrest while 12-hour lactate clearance was not. The clinical value of lactate as the sole predictor of outcome after out-of-hospital cardiac arrest is, however, limited.
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3.
  • Lilja, Gisela, et al. (författare)
  • Effects of Hypothermia vs Normothermia on Societal Participation and Cognitive Function at 6 Months in Survivors After Out-of-Hospital Cardiac Arrest A Predefined Analysis of the TTM2 Randomized Clinical Trial
  • 2023
  • Ingår i: Jama Neurology. - 2168-6149 .- 2168-6157. ; 80:10, s. 1070-1079
  • Tidskriftsartikel (refereegranskat)abstract
    • IMPORTANCE The Targeted Hypothermia vs Targeted Normothermia After Out-of-Hospital Cardiac Arrest (TTM2) trial reported no difference in mortality or poor functional outcome at 6 months after out-of-hospital cardiac arrest (OHCA). This predefined exploratory analysis provides more detailed estimation of brain dysfunction for the comparison of the 2 intervention regimens. OBJECTIVES To investigate the effects of targeted hypothermia vs targeted normothermia on functional outcome with focus on societal participation and cognitive function in survivors 6 months after OHCA. DESIGN, SETTING, AND PARTICIPANTS This study is a predefined analysis of an international multicenter, randomized clinical trial that took place from November 2017 to January 2020 and included participants at 61 hospitals in 14 countries. A structured follow-up for survivors performed at 6 months was by masked outcome assessors. The last follow-up took place in October 2020. Participants included 1861 adult (older than 18 years) patients with OHCA who were comatose at hospital admission. At 6 months, 939 of 1861 were alive and invited to a follow-up, of which 103 of 939 declined or were missing. INTERVENTIONS Randomization 1:1 to temperature control with targeted hypothermia at 33 degrees C or targeted normothermia and early treatment of fever (37.8 degrees C or higher). MAIN OUTCOMES AND MEASURES Functional outcome focusing on societal participation assessed by the Glasgow Outcome Scale Extended ([GOSE] 1 to 8) and cognitive function assessed by the Montreal Cognitive Assessment ([MoCA] 0 to 30) and the Symbol Digit Modalities Test ([SDMT] z scores). Higher scores represent better outcomes. RESULTS At 6 months, 836 of 939 survivors with a mean age of 60 (SD, 13) (range, 18 to 88) years (700 of 836 male [84%]) participated in the follow-up. There were no differences between the 2 intervention groups in functional outcome focusing on societal participation (GOSE score, odds ratio, 0.91; 95% CI, 0.71-1.17; P =.46) or in cognitive function by MoCA (mean difference, 0.36; 95% CI,-0.33 to 1.05; P =.37) and SDMT (mean difference, 0.06; 95% CI,-0.16 to 0.27; P =.62). Limitations in societal participation (GOSE score less than 7) were common regardless of intervention (hypothermia, 178 of 415 [43%]; normothermia, 168 of 419 [40%]). Cognitive impairment was identified in 353 of 599 survivors (59%). CONCLUSIONS In this predefined analysis of comatose patients after OHCA, hypothermia did not lead to better functional outcome assessed with a focus on societal participation and cognitive function than management with normothermia. At 6 months, many survivors had not regained their pre-arrest activities and roles, and mild cognitive dysfunction was common.
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4.
  • Dankiewicz, Josef, et al. (författare)
  • Targeted hypothermia versus targeted Normothermia after out-of-hospital cardiac arrest (TTM2): A randomized clinical trial - Rationale and design
  • 2019
  • Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 217, s. 23-31
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Less than 500 participants have been included in randomized trials comparing hypothermia with regular care for out-of-hospital cardiac arrest patients, and many of these trials were small and at a high risk of bias. Consequently, the accrued data on this potentially beneficial intervention resembles that of a drug following small phase II trials. A large confirmatory trial is therefore warranted. Methods: The TTM2-trial is an international, multicenter, parallel group, investigator-initiated, randomized, superiority trial in which a target temperature of 33°C after cardiac arrest will be compared with a strategy to maintain normothermia and early treatment of fever (≥37.8°C). Participants will be randomized within 3 hours of return of spontaneous circulation with the intervention period lasting 40 hours in both groups. Sedation will be mandatory for all patients throughout the intervention period. The clinical team involved with direct patient care will not be blinded to allocation group due to the inherent difficulty in blinding the intervention. Prognosticators, outcome-assessors, the steering group, the trial coordinating team, and trial statistician will be blinded. The primary outcome will be all-cause mortality at 180 days after randomization. We estimate a 55% mortality in the control group. To detect an absolute risk reduction of 7.5% with an alpha of 0.05 and 90% power, 1900 participants will be enrolled. The main secondary neurological outcome will be poor functional outcome (modified Rankin Scale 4–6) at 180 days after arrest. Discussion: The TTM2-trial will compare hypothermia to 33°C with normothermia and early treatment of fever (≥37.8°C) after out-of-hospital cardiac arrest. © 2019
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5.
  • Tengberg, A., et al. (författare)
  • Evaluation of a lifetime-based optode to measure oxygen in aquatic systems
  • 2006
  • Ingår i: Limnology and Oceanography. - : Wiley. - 1541-5856. ; 4:FEB, s. 7-17
  • Tidskriftsartikel (refereegranskat)abstract
    • In this article, we evaluate the performance of a commercially available lifetime-based optode and compare it with data obtained by other methods. We performed a set of 10 different tests, including targeted laboratory evaluations and field studies, covering a wide range of situations from shallow coastal waters and wastewater treatment plants to abyssal depths. Our principal conclusion is that, owing to high accuracy (+/- 2 mu M), long-term stability (more than 20 months), lack of pressure hysteresis, and limited cross-sensitivity, this method is overall more suitable for oxygen monitoring than other methods.
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6.
  • Atamanchuk, Dariia, 1987, et al. (författare)
  • Continuous long-term observations of the carbonate system dynamics in the water column of a temperate fjord
  • 2015
  • Ingår i: Journal of Marine Systems. - : Elsevier BV. - 0924-7963. ; 148, s. 272-284
  • Tidskriftsartikel (refereegranskat)abstract
    • A cabled underwater observatory with more than 30 sensors delivering data in real-time was used to study the dynamics of the upper pelagic carbonate system of the Koljo Fjord, western Sweden, from September to April during two consecutive years (2011-2012 and 2012-2013). In the dynamic upper ca 15 m of the water column, salinity and temperature varied by up to 10 and 20 degrees C throughout the recorded periods, respectively. Partial pressure of CO2 (pCO(2)), measured with newly developed optical sensors (optodes) at three water depths (5, 9.6 and 12.6 m), varied between 210-940 mu atm, while O-2 varied between 80-470 mu mol/L. Redfield scaled graphs (Delta O-2:Delta DIC = -1.30), in which DIC was derived from pH or pCO(2) and salinity-derived alkalinity (A(Tsal)), and oxygen was measured by the sensors, were used as a tool to assess timing and occurrence of different processes influencing the dynamics of these parameters. Distinctive short-term variations of pCO(2) and O-2 were induced by either tidal oscillations, wind-driven water mass transport in the mixed layer or occasional transport of deep-basin water from below the thermo/halodine to the surface layer. Intensified air-sea gas exchange during short storm events was usually followed by stabilization of gas-related parameters in the water column, such as O-2 concentration and pCO(2), on longer time-scales characteristic for each parameter. Biological processes including organic matter degradation in late summer/autumn and primary production in early spring were responsible for slower and gradual seasonal changes of pCO(2) and O-2. Net primary production (NPP) rates in the Koljo Fjord were quantified to be 1.79 and 2.10 g C m(-2) during the spring bloom periods in 2012 and 2013, respectively, and ratios of 02 production:DIC consumption during the same periods were estimated to be -1.21 +/- 0.02 (at 5 m depth in 2013), -1.51 +/- 0.02 (at 12.6 m in 2012) and -1.95 +/- 0.05 (at 9.6 m in 2013). These ratios are discussed and compared to previously reported 02:C ratios during primary production. (C) 2015 Elsevier B.V. All rights reserved.
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9.
  • Thomas, P. J., et al. (författare)
  • The use of novel optode sensor technologies for monitoring dissolved carbon dioxide and ammonia concentrations under live haul conditions
  • 2017
  • Ingår i: Aquacultural Engineering. - : Elsevier BV. - 0144-8609. ; 77, s. 89-96
  • Tidskriftsartikel (refereegranskat)abstract
    • Fish health under live haul transportation on wellboats and in other recirculating aquaculture systems depends on frequent and reliable measurements of water quality, that may change in response to changes in the environmental conditions and treatment processes. While reliable technologies exist for sensors measuring some water quality parameters such as Oxygen concentration and salinity, there is a lack of sensor technologies for the measurement of other critical water quality parameters such as water pCO(2) and NH3 concentrations. Presented is the theory of operation and performance of prototype optical sensors for the measurement of pCO(2) and NH3, as well as the methods used for their calibration and characterization. In order to evaluate the sensor's suitability for aquaculture applications we temporarily installed the sensors on a weliboat and monitored the water quality during the transportation of live mature Atlantic salmon between fish farms and slaughter facilities on the Norwegian coast. Under transportation with different stocking weights and recirculation conditions, the CO2 optode prototypes recorded measurements that coincided with measurements from standard laboratory analysis of spot samples. The pCO(2) concentration in the well throughout the testing was shown to vary between approximately 300ilatm and 20 000 atm. Compared to the pH derived pCO(2) estimation method widely applied in aquaculture, the CO2 optode was more sensitive to small fluctuations in CO2 concentration, and gave measurements closer to the CO2 values recorded by laboratory analysis of spot samples. The NH3 optode reported measurements that were consistent with spot samples analyzed using the salicylate-hypochlorite reaction. In contrast to pCO(2), the concentration of NH3 during the observed weliboat missions was found to be very low and stable at 0.8 0.31.4L(-1). Once fully developed, the CO2 and NH3 optodes could contribute to better water quality control and efficiency during well boat transportations and other recirculating aquaculture systems. (C) 2017 Published by Elsevier B.V.
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10.
  • Atamanchuk, Dariia, 1987, et al. (författare)
  • Performance of a lifetime-based optode for measuring partial pressure of carbon dioxide in natural waters
  • 2014
  • Ingår i: Limnology and Oceanography : Methods. - : Wiley. - 1541-5856. ; 12, s. 63-73
  • Tidskriftsartikel (refereegranskat)abstract
    • This article reports the performance of an improved, newly developed, compact, low power, lifetime-based optical sensor (optode) for measuring partial pressure of dissolved CO2 gas (pCO2) in natural waters. The results suggest that after preconditioning, these sensors are stable in water for time periods longer than 7 months. The wide dynamic range of about 0-50000 μatm opens possibilities for numerous applications of which some are presented. In normal marine environments with pCO2 levels of 200-1000 μatm, the best-obtained precision was about ±2 μatm, and the absolute accuracy was between 2-75 μatm, depending on the deployment and the quality of the collected reference water samples. One limitation is that these sensors will become irreversibly poisoned by H2S and should thus not be deployed in sulphidic environments.
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11.
  • Gagnon, David J., et al. (författare)
  • Prophylactic antibiotics are associated with a lower incidence of pneumonia in cardiac arrest survivors treated with targeted temperature management
  • 2015
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 92, s. 154-159
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Prophylactic antibiotics (PRO) reduce the incidence of early-onset pneumonia in comatose patients with structural brain injury, but have not been examined in cardiac arrest survivors undergoing targeted temperature management (TTM). We investigated the effect of PRO on the development of pneumonia in that population. Methods: We conducted a retrospective cohort study comparing patients treated with PRO to those not receiving PRO (no-PRO) using Northern Hypothermia Network registry data. Cardiac arrest survivors >= 18 years of age with a GCS < 8 at hospital admission and treated with TTM at 32-34 degrees C were enrolled in the registry. Differences were analyzed in univariate analyses and with logistic regression models to evaluate independent associations of clinical factors with incidence of pneumonia and good functional outcome. Results: 416 of 1240 patients (33.5%) received PRO. Groups were similar in age, gender, arrest location, initial rhythm, and time from collapse to return of spontaneous circulation. PRO patients had less pneumonia (12.6% vs. 54.9%, p < 0.001) and less sepsis (1.2 vs. 5.7%, p < 0.001) compared to no-PRO patients. ICU length of stay (98 vs. 100 h, p = 0.2) and incidence of a good functional outcome (41.1 vs. 36.6%, p = 0.19) were similar between groups. Backwards stepwise logistic regression demonstrated PRO were independently associated with a lower incidence of pneumonia (OR 0.09, 95% 0.06-0.14, p < 0.001) and a similar incidence of good functional outcome. Conclusions: Prophylactic antibiotics were associated with a reduced incidence of pneumonia but a similar rate of good functional outcome.
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12.
  • Holgersson, Johan, et al. (författare)
  • Hypothermic versus Normothermic Temperature Control after Cardiac Arrest
  • 2022
  • Ingår i: NEJM Evidence. - 2766-5526. ; 1:11, s. 1-13
  • 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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13.
  • Lilja, Gisela, et al. (författare)
  • Protocol for outcome reporting and follow-up in the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2)
  • 2020
  • Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 150, s. 104-112
  • 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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14.
  • Nielsen, Niklas, et al. (författare)
  • Outcome, timing and adverse events in therapeutic hypothermia after out-of-hospital cardiac arrest
  • 2009
  • Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley. - 0001-5172 .- 1399-6576. ; 53:7, s. 926-34
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Therapeutic hypothermia (TH) after cardiac arrest protects from neurological sequels and death and is recommended in guidelines. The Hypothermia Registry was founded to the monitor outcome, performance and complications of TH. METHODS: Data on out-of-hospital cardiac arrest (OHCA) patients admitted to intensive care for TH were registered. Hospital survival and long-term outcome (6-12 months) were documented using the Cerebral Performance Category (CPC) scale, CPC 1-2 representing a good outcome and 3-5 a bad outcome. RESULTS: From October 2004 to October 2008, 986 TH-treated OHCA patients of all causes were included in the registry. Long-term outcome was reported in 975 patients. The median time from arrest to initiation of TH was 90 min (interquartile range, 60-165 min) and time to achieving the target temperature (< or =34 degrees C) was 260 min (178-400 min). Half of the patients underwent coronary angiography and one-third underwent percutaneous coronary intervention (PCI). Higher age, longer time to return of spontaneous circulation, lower Glasgow Coma Scale at admission, unwitnessed arrest and initial rhythm asystole were all predictors of bad outcome, whereas time to initiation of TH and time to reach the goal temperature had no significant association. Bleeding requiring transfusion occurred in 4% of patients, with a significantly higher risk if angiography/PCI was performed (2.8% vs. 6.2%P=0.02). CONCLUSIONS: Half of the patients survived, with >90% having a good neurological function at long-term follow-up. Factors related to the timing of TH had no apparent association to outcome. The incidence of adverse events was acceptable but the risk of bleeding was increased if angiography/PCI was performed.
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15.
  • Simpson, Rupert F.G., et al. (författare)
  • Speed of cooling after cardiac arrest in relation to the intervention effect : a sub-study from the TTM2-trial
  • 2022
  • Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26:1
  • Tidskriftsartikel (refereegranskat)abstract
    • 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.
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16.
  • Taccone, Fabio Silvio, et al. (författare)
  • Hypothermia vs Normothermia in Patients With Cardiac Arrest and Nonshockable Rhythm : A Meta-Analysis
  • 2024
  • Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 81:2, s. 126-133
  • Tidskriftsartikel (refereegranskat)abstract
    • Importance  International guidelines recommend body temperature control below 37.8 °C in unconscious patients with out-of-hospital cardiac arrest (OHCA); however, a target temperature of 33 °C might lead to better outcomes when the initial rhythm is nonshockable.Objective  To assess whether hypothermia at 33 °C increases survival and improves function when compared with controlled normothermia in unconscious adults resuscitated from OHCA with initial nonshockable rhythm.Data Sources  Individual patient data meta-analysis of 2 multicenter, randomized clinical trials (Targeted Normothermia after Out-of-Hospital Cardiac Arrest [TTM2; NCT02908308] and HYPERION [NCT01994772]) with blinded outcome assessors. Unconscious patients with OHCA and an initial nonshockable rhythm were eligible for the final analysis.Study Selection  The study cohorts had similar inclusion and exclusion criteria. Patients were randomized to hypothermia (target temperature 33 °C) or normothermia (target temperature 36.5 to 37.7 °C), according to different study protocols, for at least 24 hours. Additional analyses of mortality and unfavorable functional outcome were performed according to age, sex, initial rhythm, presence or absence of shock on admission, time to return of spontaneous circulation, lactate levels on admission, and the cardiac arrest hospital prognosis score.Data Extraction and Synthesis  Only patients who experienced OHCA and had a nonshockable rhythm with all causes of cardiac arrest were included. Variables from the 2 studies were available from the original data sets and pooled into a unique database and analyzed. Clinical outcomes were harmonized into a single file, which was checked for accuracy of numbers, distributions, and categories. The last day of follow-up from arrest was recorded for each patient. Adjustment for primary outcome and functional outcome was performed using age, gender, time to return of spontaneous circulation, and bystander cardiopulmonary resuscitation.Main Outcomes and Measures  The primary outcome was mortality at 3 months; secondary outcomes included unfavorable functional outcome at 3 to 6 months, defined as a Cerebral Performance Category score of 3 to 5.Results  A total of 912 patients were included, 490 from the TTM2 trial and 422 from the HYPERION trial. Of those, 442 had been assigned to hypothermia (48.4%; mean age, 65.5 years; 287 males [64.9%]) and 470 to normothermia (51.6%; mean age, 65.6 years; 327 males [69.6%]); 571 patients had a first monitored rhythm of asystole (62.6%) and 503 a presumed noncardiac cause of arrest (55.2%). At 3 months, 354 of 442 patients in the hypothermia group (80.1%) and 386 of 470 patients in the normothermia group (82.1%) had died (relative risk [RR] with hypothermia, 1.04; 95% CI, 0.89-1.20; P = .63). On the last day of follow-up, 386 of 429 in the hypothermia group (90.0%) and 413 of 463 in the normothermia group (89.2%) had an unfavorable functional outcome (RR with hypothermia, 0.99; 95% CI, 0.87-1.15; P = .97). The association of hypothermia with death and functional outcome was consistent across the prespecified subgroups.Conclusions and Relevance  In this individual patient data meta-analysis, including unconscious survivors from OHCA with an initial nonshockable rhythm, hypothermia at 33 °C did not significantly improve survival or functional outcome.
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