For outcomes research where changes in intraoperative blood pressure are a possible causative factor, it is important to determine an appropriate source for a reference value. We studied to what ...extent preinduction blood pressure values in the operating room differ from those obtained during preoperative evaluation outside the operating room.
Cohort study including 4408 patients aged 60 years or older undergoing noncardiac surgery. The outcome was the difference between the preinduction mean blood pressure (MBP) and the MBP obtained during preoperative evaluation. A difference of ≥10 mm Hg was considered clinically relevant. A paired samples t test was used to estimate the difference. Linear regression was used to obtain estimates adjusted for patient characteristics, comorbidity, medications, type of surgery, and preoperative blood pressure.
Complete data were available for 3660 (83%) patients. There were 2228 (61%) patients with a difference of ≥10 mm Hg between the preinduction and preoperative MBP. The overall mean difference between both MBPs was 11 mm Hg (95% confidence interval, 10-11) with important variability among individuals. Patients with higher preoperative MBP values had smaller differences. After adjusting for patient characteristics, comorbidity, medications, type of surgery, and preoperative blood pressure, the difference decreased an estimated 5.0 mm Hg (95% confidence interval, 4.7-5.4) for every increase of 10 mm Hg in preoperative MBP. Patient characteristics, comorbidity, type of surgery, or medication were not strongly associated with the difference.
The average preinduction blood pressure was higher than the preoperative blood pressure. This difference between the measurements can be explained by stress-induced effects and regression to the mean. To define an optimal reference value for research purposes or to arrive at a clinical perioperative blood pressure target, one should consider that there is important variability both within and between patients.
Objectives
To describe the association between intensive care unit (ICU) delirium and self‐reported cognitive problems in 1‐year ICU survivors, and investigate whether this association was altered by ...exposure to systemic inflammation during ICU stay.
Design
Prospective cohort study.
Setting
Dutch medical‐surgical ICU.
Participants
One‐year ICU survivors, admitted to the ICU ≥48 hours.
Measurements
Self‐reported cognitive problems were measured with the Cognitive Failures Questionnaire (CFQ). Cumulative exposure to systemic inflammation was based on all daily C‐reactive protein (CRP) measurements during ICU stay, expressed as the area under the curve (AUC). Multivariable linear regression was conducted to evaluate the association between delirium and the CFQ. The effect of inflammation on the association between delirium and CFQ was assessed, comparing the effect estimate (B) of delirium and CFQ between models with and without inclusion of the AUC of CRP.
Results
Among 567 1‐year ICU survivors, the CFQ was completed by 363 subjects. Subjects with multiple days of delirium during ICU stay reported more self‐reported cognitive problems (Badj = 5.10, 95% CI 1.01–9.20), whereas a single day delirium was not associated with higher CFQ scores (Badj = −0.72, 95% CI −5.75 to 4.31). Including the AUC of CRP did not change the association between delirium and the CFQ (ratio for a single and multiple days were respectively: 1.00, 95%CI 0.59–1.44 and 0.86, 95% CI 0.47–1.16).
Conclusion
Multiple days of delirium was associated with long‐term self‐reported cognitive problems. The cumulative exposure to systemic inflammation did not alter this association, suggesting that delirium in the context of little inflammation is also detrimental.
Cytomegalovirus (CMV) reactivation in previously immunocompetent critically ill patients is associated with increased mortality, which has been hypothesized to result from virus-induced ...immunomodulation. Therefore, we studied the effects of CMV reactivation on the temporal course of host response biomarkers in patients with sepsis.
In this matched cohort study, each sepsis patient developing CMV reactivation between day 3 and 17 (CMV+) was compared with one CMV seropositive patient without reactivation (CMVs+) and one CMV seronegative patient (CMVs-). CMV serostatus and plasma loads were determined by enzyme-linked immunoassays and real-time polymerase chain reaction, respectively. Systemic interleukin-6 (IL-6), IL-8, IL-18, interferon-gamma-induced protein-10 (IP-10), neutrophilic elastase, IL-1 receptor antagonist (RA), and IL-10 were measured at five time points by multiplex immunoassay. The effects of CMV reactivation on sequential concentrations of these biomarkers were assessed in multivariable mixed models.
Among 64 CMV+ patients, 45 could be matched to CMVs+ or CMVs- controls or both. The two baseline characteristics and host response biomarker levels at viremia onset were similar between groups. CMV+ patients had increased IP-10 on day 7 after viremia onset (symmetric percentage difference +44% versus -15% when compared with CMVs+ and +37% versus +4% when compared with CMVs-) and decreased IL-1RA (-41% versus 0% and -49% versus +10%, respectively). However, multivariable analyses did not show an independent association between CMV reactivation and time trends of IL-6, IP-10, IL-10, or IL-1RA.
CMV reactivation was not independently associated with changes in the temporal trends of host response biomarkers in comparison with non-reactivating patients. Therefore, these markers should not be used as surrogate clinical endpoints for interventional studies evaluating anti-CMV therapy.
The aim of this study was to investigate whether in-hospital mortality was associated with the administered fraction of oxygen in inspired air (FiO2) and achieved arterial partial pressure of oxygen ...(PaO2).
This was a retrospective, observational study on data from the first 24 h after admission from 36,307 consecutive patients admitted to 50 Dutch intensive care units (ICUs) and treated with mechanical ventilation. Oxygenation data from all admission days were analysed in a subset of 3,322 patients in 5 ICUs.
Mean PaO2 and FiO2 in the first 24 h after ICU admission were 13.2 kPa (standard deviation (SD) 6.5) and 50% (SD 20%) respectively. Mean PaO2 and FiO2 from all admission days were 12.4 kPa (SD 5.5) and 53% (SD 18). Focusing on oxygenation in the first 24 h of admission, in-hospital mortality was shown to be linearly related to FiO2 value and had a U-shaped relationship with PaO2 (both lower and higher PaO2 values were associated with a higher mortality), independent of each other and of Simplified Acute Physiology Score (SAPS) II, age, admission type, reduced Glasgow Coma Scale (GCS) score, and individual ICU. Focusing on the entire ICU stay, in-hospital mortality was independently associated with mean FiO2 during ICU stay and with the lower two quintiles of mean PaO2 value during ICU stay.
Actually achieved PaO2 values in ICU patients in The Netherlands are higher than generally recommended in the literature. High FiO2, and both low PaO2 and high PaO2 in the first 24 h after admission are independently associated with in-hospital mortality in ICU patients. Future research should study whether this association is causal or merely a reflection of differences in severity of illness insufficiently corrected for in the multivariate analysis.
Statins are thought to have pleiotropic properties, including anticoagulant effects, in addition to reducing lipoprotein (LDL) levels. Plasma extracellular vesicles (EVs) are small bilayer membrane ...vesicles involved in various biological processes including coagulation. Since subsets of EVs in the LDL plasma fraction (LDL-EVs) correlate with thrombin activity, we hypothesized that changes in LDL-EVs after statin therapy may differ from that of serum levels of coagulation proteins, providing insight into the effects of statins on coagulation.
The study was conducted in 666 subjects with available serum from the METEOR trial, a trial of the effect of rosuvastatin versus placebo in patients with subclinical atherosclerosis. Changes in protein levels of von Willebrand Factor (VWF), SerpinC1 and plasminogen were measured in serum and in LDL-EVs, and were compared between the rosuvastatin and placebo groups.
LDL-EV levels of plasminogen and VWF increased with rosuvastatin treatment compared to placebo (mean change of 126 ± 8 versus 17 ± 12 μg/mL for plasminogen (p < 0.001) and 310 ± 60 versus 64 ± 55 μg/mL for VWF (p = 0.015)). There was no difference between groups for change in LDL-EV-SerpinC1. In contrast, serum plasminogen levels increased to a lesser extent with rosuvastatin compared to placebo (23 ± 29 versus 67 ± 17 μg/mL, p = 0.024) and serum VWF levels showed no significant difference between both groups.
Rosuvastatin increases LDL-EV coagulation proteins plasminogen and VWF in patients with subclinical atherosclerosis, an effect that is different from the effect of rosuvastatin on the same proteins in serum. This identifies LDL-EVs as a newly detected possible intermediate between statin therapy and coagulation.
•LDL associated extracellular vesicles (LDL-EVs) are involved coagulation processes.•This study investigates the effect of statins on coagulation proteins in LDL-EVs.•Rosuvastatin increases plasminogen and von Willebrand factor in LDL-EVs.•LDL-EVs are identified as a possible intermediate between statins and coagulation.
Prognostic factors for the combination of long-term survival and health-related quality of life (HRQoL) after intensive care unit (ICU) stay have not yet been studied. Our aim was to assess whether ...early acute kidney injury (eAKI), AKI occurring on the first day of ICU admission, is an independent predictor of this combined one-year outcome.
We included all patients admitted to the mixed ICU of the University Medical Centre Utrecht between July 2009 and April 2013, excluding patients with chronic dialysis, cardiac surgery, and length of stay shorter than 24 hours. eAKI was defined using the risk, injury, failure, loss, end-stage renal failure (RIFLE) classification, using a newly developed algorithm to classify AKI based on routinely collected patient data. In one-year survivors, HRQoL was measured using the EuroQoL 5D-3L™ (EQ-5D) questionnaire. The primary outcome measure was "poor outcome", defined as an EQ-5D index score <0.4 or death after one year follow up. A multivariable Poisson regression model was performed to adjust for age, comorbidities, admission type and severity of disease factors.
We enrolled 2,420 patients, of whom 871 (36.0 %) died within one year. An additional 286 of 1549 one-year survivors (11.8 %) experienced low HRQoL. The respective incidence of the RIFLE classes, risk, injury and failure, were 456 (18.8 %), 253 (10.5 %) and 123 (5.1 %). After adjustment for other covariates, the RIFLE classes, injury and failure, were independently associated with poor outcome (adjusted relative risk 1.14, 95 % CI 1.01, 1.29; p = 0.03, and 1.25, 95 % CI 1.01, 1.55; p = 0.04), when compared to no eAKI patients . The constituents of this composite outcome were also analysed separately. In a Cox regression model the RIFLE classes, injury and failure, were significantly associated with mortality (adjusted hazard ratio 1.35, 95 % CI 1.11, 1.65; p <0.01, and 1.78, 95 % CI 1.38, 2.30; p <0.01). In one-year survivors specifically, none of the RIFLE classes were significantly associated with low HRQoL.
ICU patients with moderate or severe AKI during the first 24 hours have a higher probability of mortality or low HRQoL (combined poor outcome), one year after ICU admission. Together with other available early prognostic factors, information on early acute kidney injury could improve informed decision-making on the continuation or withdrawal of treatment in ICU patients.
Cardiac surgery and postoperative admission to the ICU may lead to posttraumatic stress disorder and depression. Perioperatively administered corticosteroids potentially alter the risk of development ...of these psychiatric conditions, by affecting the hypothalamic-pituitary-adrenal axis. However, findings of previous studies are inconsistent. We aimed to assess the effect of a single dose of dexamethasone compared with placebo on symptoms of posttraumatic stress disorder and depression and health-related quality of life after cardiac surgery and ICU admission.
Follow-up study of a randomized clinical trial.
Five Dutch heart centers.
Cardiac surgery patients (n = 1,244) who participated in the Dexamethasone for Cardiac Surgery trial.
A single intraoperative IV dose of dexamethasone or placebo was administered in a randomized, double-blind way.
Symptoms of posttraumatic stress disorder, depression, and health-related quality of life were assessed with validated questionnaires 1.5 years after randomization. Data were available for 1,125 patients (90.4%); of which 561 patients received dexamethasone and 564 patients received placebo. Overall, the prevalence of psychopathology was not influenced by dexamethasone. Posttraumatic stress disorder and depression were present in, respectively, 52 patients (9.3%) and 69 patients (12.3%) who received dexamethasone and in 66 patients (11.7%) and 78 patients (13.8%) who received placebo (posttraumatic stress disorder: odds ratio, 0.82; 95% CI, 0.55-1.20; p = 0.30; depression: odds ratio, 0.92; 95% CI, 0.64-1.31; p = 0.63). Subgroup analysis revealed a lower prevalence of posttraumatic stress disorder (odds ratio, 0.23; 95% CI, 0.07-0.72; p < 0.01) and depression (odds ratio, 0.29; 95% CI, 0.11-0.77; p < 0.01) in female patients after dexamethasone administration. Health-related quality of life did not differ between groups and was not associated with psychopathology.
Overall, our findings suggest that exogenous administration of the glucocorticoid receptor agonist dexamethasone-compared with placebo-during cardiac surgery does not positively or negatively affect the prevalence of posttraumatic stress disorder and depression. However, in female patients, beneficial effects on the occurrence of posttraumatic stress disorder and depression may be present.
Objective The aim of this study was to investigate whether acute kidney injury (AKI) after coronary artery bypass grafting can be attributed to intraoperative hypotension during cardiopulmonary ...bypass (IOH-CPB). Design Retrospective analysis. Setting Tertiary-care hospital. Participants Patients undergoing on-pump coronary artery bypass grafting from June 2011 to January 2014. Interventions None. Measurements and Main Results IOH-CPB was defined as blood pressure below several absolute and relative mean arterial pressure (MAP) thresholds and as the area under the curve for absolute MAP thresholds. AKI was defined as an absolute increase in serum creatinine of≥26 µmol/L within 48 hours or an increase to 150% or more within 7 days of surgery. Poisson regression with robust standard errors both before and after adjustment for confounders was used. Of the 1,891 patients included, 386 (20%) developed AKI. In univariable analysis, all IOH-CPB thresholds defined as a MAP of 50 mmHg or less and as a decrease in MAP of 60% from baseline were associated with a 1.07-to-1.11 times increased risk of AKI per 10 minutes of IOH-CPB (p<0.01). After adjustment for potential confounders, IOH-CPB, irrespective of the definition chosen, was not associated with an increased risk of AKI. Conclusions In the authors’ study population, univariable analysis showed an association of IOH-CPB with AKI in patients undergoing isolated CABG, but this relationship disappeared after correction for well-known risk factors for AKI.
Purpose
Delirium is a common disorder in intensive care unit (ICU) patients. It is unclear whether ICU environment affects delirium. We investigated the influence of ICU environment on the number of ...days with delirium during ICU admission.
Methods
In this prospective before–after study, ICU delirium was compared between a conventional ICU with wards and a single-room ICU with, among others, improved daylight exposure. We included patients admitted for more than 24 h between March and June 2009 (ICU with wards) or between June and September 2010 (single-room ICU). Patients who remained unresponsive throughout ICU admission were excluded. The presence of delirium in the preceding 24 h was assessed daily with the confusion assessment method for the ICU (CAM-ICU) by research physicians combined with evaluation of medical and nursing charts. The number of days with delirium was investigated with Poisson regression analysis.
Results
We included 55 patients (449 observation days) in the ICU with wards and 75 patients (468 observation days) in the single-room ICU. After adjusting for confounding, the number of days with delirium decreased by 0.4 days (95 % confidence interval 0.1–0.7) in the single-room ICU (
p
= 0.005). The incidence of delirium during ICU stay was similar in the ICU with wards (51 %) and in the single-room ICU (45 %,
p
= 0.53).
Conclusions
This study is the first to show that ICU environment may influence the course of delirium in ICU patients.
Background
Patients who survive after an aneurysmal subarachnoid haemorrhage (ASAH) have an increased incidence of cardiovascular events compared with the general population. We assessed whether ...troponin elevation after aneurysm occlusion, as marker of myocardial injury, can predict long-term cardiac events.
Methods
We analysed a prospectively collected cohort of 159 patients with ASAH and early aneurysm occlusion, in whom routine post-intervention troponin I (TnI) measurements were performed. With competing risk regression modelling we estimated the association between TnI elevation after aneurysm occlusion and major adverse cardiac events within one year. Secondary outcome measures were all-cause mortality and neurological condition within one year. The predictive value of post-intervention TnI was compared with the predictive value of pre-intervention characteristics using c-statistics and the integrated discrimination improvement index.
Results
Subdistribution hazard ratios for TnI elevation and major adverse cardiac events at one year were 1.05 (95% confidence interval (CI) 1.03–1.07) per 10 ng/l increase in TnI and 7.91 (95% CI 1.46–43.0) for any TnI elevation. After adjustment for pre-intervention variables, the subdistribution hazard ratios were 1.47 (95% CI 0.81–2.67) per 10 ng/l and 9.00 (95% CI 1.62–50.1) for any elevation. The c-statistic was 0.71 for TnI elevation as a continuous measure and 0.69 for any TnI elevation. The integrated discrimination improvement index showed a minimum improvement in prediction of 0.08 (interquartile range 0.06 to 0.09) for TnI as a continuous measure and 0.003 (interquartile range −0.004 to 0.01) for any TnI elevation, when compared with pre-intervention characteristics.
Conclusion
TnI elevation after occlusion of a ruptured intracranial aneurysm predicts the occurrence of a major adverse cardiac event within one year after ASAH.
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