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| 2. |
- Dankiewicz, Josef, et al.
(författare)
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Hypothermia versus Normothermia after Out-of-Hospital Cardiac Arrest
- 2021
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 384:24, s. 2283-2294
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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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| 3. |
- 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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| 4. |
- Robba, Chiara, et al.
(författare)
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Ventilatory settings in the initial 72 h and their association with outcome in out-of-hospital cardiac arrest patients : a preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after out-of-hospital cardiac arrest (TTM2) trial
- 2022
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Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 48:8, s. 1024-1038
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The optimal ventilatory settings in patients after cardiac arrest and their association with outcome remain unclear. The aim of this study was to describe the ventilatory settings applied in the first 72 h of mechanical ventilation in patients after out-of-hospital cardiac arrest and their association with 6-month outcomes. Methods: Preplanned sub-analysis of the Target Temperature Management-2 trial. Clinical outcomes were mortality and functional status (assessed by the Modified Rankin Scale) 6 months after randomization. Results: A total of 1848 patients were included (mean age 64 [Standard Deviation, SD = 14] years). At 6 months, 950 (51%) patients were alive and 898 (49%) were dead. Median tidal volume (VT) was 7 (Interquartile range, IQR = 6.2–8.5) mL per Predicted Body Weight (PBW), positive end expiratory pressure (PEEP) was 7 (IQR = 5–9) cmH20, plateau pressure was 20 cmH20 (IQR = 17–23), driving pressure was 12 cmH20 (IQR = 10–15), mechanical power 16.2 J/min (IQR = 12.1–21.8), ventilatory ratio was 1.27 (IQR = 1.04–1.6), and respiratory rate was 17 breaths/minute (IQR = 14–20). Median partial pressure of oxygen was 87 mmHg (IQR = 75–105), and partial pressure of carbon dioxide was 40.5 mmHg (IQR = 36–45.7). Respiratory rate, driving pressure, and mechanical power were independently associated with 6-month mortality (omnibus p-values for their non-linear trajectories: p < 0.0001, p = 0.026, and p = 0.029, respectively). Respiratory rate and driving pressure were also independently associated with poor neurological outcome (odds ratio, OR = 1.035, 95% confidence interval, CI = 1.003–1.068, p = 0.030, and OR = 1.005, 95% CI = 1.001–1.036, p = 0.048). A composite formula calculated as [(4*driving pressure) + respiratory rate] was independently associated with mortality and poor neurological outcome. Conclusions: Protective ventilation strategies are commonly applied in patients after cardiac arrest. Ventilator settings in the first 72 h after hospital admission, in particular driving pressure and respiratory rate, may influence 6-month outcomes.
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| 5. |
- Jammer, Ib, et al.
(författare)
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Standards for definitions and use of outcome measures for clinical effectiveness research in perioperative medicine: European Perioperative Clinical Outcome (EPCO) definitions: A statement from the ESA-ESICM joint taskforce on perioperative outcome measures.
- 2015
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Ingår i: European Journal of Anaesthesiology. - : Lippincott Williams & Wilkins. - 1365-2346 .- 0265-0215. ; 32:2, s. 88-105
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for large trials that test the clinical effectiveness of interventions in the field of perioperative medicine. Clinical outcome measures used in such trials must be robust, clearly defined and patient-relevant. Our objective was to develop standards for the use of clinical outcome measures to strengthen the methodological quality of perioperative medicine research. A literature search was conducted using PubMed and opinion leaders worldwide were invited to nominate papers that they believed the group should consider. The full texts of relevant articles were reviewed by the taskforce members and then discussed to reach a consensus on the required standards. The report was then circulated to opinion leaders for comment and review. This report describes definitions for 22 individual adverse events with a system of severity grading for each. In addition, four composite outcome measures were identified, which were designed to evaluate postoperative outcomes. The group also agreed on standards for four outcome measures for the evaluation of healthcare resource use and quality of life. Guidance for use of these outcome measures is provided, with particular emphasis on appropriate duration of follow-up. This report provides clearly defined and patient-relevant outcome measures for large clinical trials in perioperative medicine. These outcome measures may also be of use in clinical audit. This report is intended to complement and not replace other related work to improve assessment of clinical outcomes following specific surgical procedures.
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| 6. |
- Kreu, S., et al.
(författare)
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Alkalosis in Critically III Patients with Severe Sepsis and Septic Shock
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Although metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock. This is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS). Metabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset > 48 hours) were the only significant predictor of increased ICU length of stay. Metabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay.
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| 7. |
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| 8. |
- Bergenzaun, Lill, et al.
(författare)
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Assessing left ventricular systolic function in shock : evaluation of echocardiographic parameters in intensive care
- 2011
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Ingår i: Critical Care. - : BioMed Central. - 1364-8535 .- 1466-609X. ; 15:4
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Assessing left ventricular (LV) systolic function in a rapid and reliable way can be challenging in the critically ill patient. The purpose of this study was to evaluate the feasibility and reliability of, as well as the association between, commonly used LV systolic parameters, by using serial transthoracic echocardiography (TTE). METHODS: Fifty patients with shock and mechanical ventilation were included. TTE examinations were performed daily for a total of 7 days. Methods used to assess LV systolic function were visually estimated, "eyeball" ejection fraction (EBEF), the Simpson single-plane method, mean atrioventricular plane displacement (AVPDm), septal tissue velocity imaging (TDIs), and velocity time integral in the left ventricular outflow tract (VTI). RESULTS: EBEF, AVPDm, TDIs, VTI, and the Simpson were obtained in 100%, 100%, 99%, 95% and 93%, respectively, of all possible examinations. The correlations between the Simpson and EBEF showed r values for all 7 days ranging from 0.79 to 0.95 (P < 0.01). the Simpson correlations with the other LV parameters showed substantial variation over time, with the poorest results seen for TDIs and AVPDm. The repeatability was best for VTI (interobserver coefficient of variation (CV) 4.8%, and intraobserver CV, 3.1%), and AVPDm (5.3% and 4.4%, respectively), and worst for the Simpson method (8.2% and 10.6%, respectively). CONCLUSIONS: EBEF and AVPDm provided the best, and Simpson, the worst feasibility when assessing LV systolic function in a population of mechanically ventilated, hemodynamically unstable patients. Additionally, the Simpson showed the poorest repeatability. We suggest that EBEF can be used instead of single-plane Simpson when assessing LV ejection fraction in this category of patients. TDIs and AVPDm, as markers of longitudinal function of the LV, are not interchangeable with LV ejection fraction.
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| 9. |
- Bergström, Anna, et al.
(författare)
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Acetaminophen Attenuates Pulmonary Vascular Resistance and Pulmonary Arterial Pressure and Inhibits Cardiovascular Collapse in a Porcine Model of Endotoxemia
- 2023
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Ingår i: Shock. - : Shock Society. - 1073-2322 .- 1540-0514. ; 59:3, s. 442-448
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Tidskriftsartikel (refereegranskat)abstract
- Acetaminophen (paracetamol) is often used in critically ill patients with fever and pain; however, little is known about the effects of acetaminophen on cardiovascular function during systemic inflammation. Here, we investigated the effect of acetaminophen on changes in the systemic and pulmonary circulation induced by endotoxin (0.5 μg/kg/h) in anesthetized pigs. Endotoxin infusion led to a rapid increase in pulmonary artery (PA)-pressure and pulmonary vascular resistance index (PVRI). Acetaminophen delayed and attenuated this increase. Furthermore, acetaminophen reduced tachycardia and decreased stroke volume, accompanied by systemic inflammation, without affecting inflammatory parameters such as white blood cell count and TNF-α in blood. As a proof of concept, we injected a high dose of endotoxin (100 μg), which induced rapid cardiovascular collapse in pigs. Pigs treated with acetaminophen survived with no obvious hemodynamic instability during the 50 min observation period. In conclusion, acetaminophen attenuates the effects of endotoxin on pulmonary circulation in anesthetized pigs. This may play a role in severe systemic inflammation.
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| 10. |
- Düring, Joachim, et al.
(författare)
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Influence of temperature management at 33 °C versus normothermia on survival in patients with vasopressor support after out-of-hospital cardiac arrest : a post hoc analysis of the TTM-2 trial
- 2022
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Ingår i: Critical Care. - : Springer Science and Business Media LLC. - 1364-8535 .- 1466-609X. ; 26:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. Methods: We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP < 70 mmHg or any dose of dopamine/dobutamine or noradrenaline/adrenaline dose ≤ 0.25 µg/kg/min; and (3) high-vasopressor support, noradrenaline/adrenaline dose > 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. Results: The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78–1.39] in the no-, 1.22 [98.3% CI 0.97–1.53] in the moderate-, and 0.97 [98.3% CI 0.68–1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. Conclusions: In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308, registered September 20, 2016.
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