Purpose
Muscle wasting is common amongst patients with persistent critical illness and associated with increased urea production, but reduced creatinine production. We hypothesised that elevated ...urea:creatinine ratio would provide a biochemical signature of muscle catabolism and characterise prolonged intensive care (ICU) admissions after major trauma.
Methods
Using pre-specified hypotheses, we analysed two existing data sets of adults surviving ≥ 10 days following admission to ICU after major trauma. We analysed trauma-ICU admissions to the major trauma centre serving the North East London and Essex Trauma Network, with a verification cohort of trauma-ICU cases from the MIMIC-III database. We compared serum urea, creatinine, and urea:creatinine ratio (ratio of concentrations in mmol/L) between patients with persistent critical illness (defined as ICU stay of ≥ 10 days) and those discharged from ICU before day 10. In a sub-group undergoing sequential abdominal computerised tomography (CT), we measured change in cross-sectional muscle area (psoas muscle at L4 vertebral level and total muscle at L3 level) and assessed for relationships with urea:creatinine ratio and ICU stay. Results are provided as median interquartile range.
Results
We included 1173 patients between February 1st, 2012 and May 1st, 2016. In patients with ICU stay ≥ 10 days, day 10 urea:creatinine ratio had increased by 133% 72–215, from 62 46–78 to 141 114–178,
p
< 0.001; this rise was larger (
p
< 0.001) than in patients discharged from ICU before day 10, 59% 11–122%, 61 45–75 to 97 67–128,
p
< 0.001. A similar separation in trajectory of urea:creatinine ratio was observed in 2876 trauma-ICU admissions from MIMIC-III. In 107 patients undergoing serial CTs, decrease in L4 psoas and L3 muscle cross-sectional areas between CTs significantly correlated with time elapsed (
R
2
= 0.64 and
R
2
= 0.59, respectively). Rate of muscle decrease was significantly greater (
p
< 0.001 for interaction terms) in 53/107 patients with the second CT during evolving, current or recent persistent critical illness. In this group, at the second CT urea:creatinine ratio negatively correlated with L4 psoas and L3 muscle cross-sectional areas (
R
2
0.39,
p
< 0.001 and 0.44,
p
< 0.001).
Conclusion
Elevated urea:creatinine ratio accompanies skeletal muscle wasting representing a biochemical signature of persistent critical illness after major trauma. If prospectively confirmed, urea:creatinine ratio is a potential surrogate of catabolism to examine in epidemiological and interventional studies.
The association between intraoperative cardiovascular changes and perioperative myocardial injury has chiefly focused on hypotension during noncardiac surgery. However, the relative influence of ...blood pressure and heart rate (HR) remains unclear. We investigated both individual and codependent relationships among intraoperative HR, systolic blood pressure (SBP), and myocardial injury after noncardiac surgery (MINS).
Secondary analysis of the Vascular Events in Noncardiac Surgery Cohort Evaluation (VISION) study, a prospective international cohort study of noncardiac surgical patients. Multivariable logistic regression analysis tested for associations between intraoperative HR and/or SBP and MINS, defined by an elevated serum troponin T adjudicated as due to an ischemic etiology, within 30 days after surgery. Predefined thresholds for intraoperative HR and SBP were: maximum HR >100 beats or minimum HR <55 beats per minute (bpm); maximum SBP >160 mm Hg or minimum SBP <100 mm Hg. Secondary outcomes were myocardial infarction and mortality within 30 days after surgery.
After excluding missing data, 1197 of 15,109 patients (7.9%) sustained MINS, 454 of 16,031 (2.8%) sustained myocardial infarction, and 315 of 16,061 patients (2.0%) died within 30 days after surgery. Maximum intraoperative HR >100 bpm was associated with MINS (odds ratio OR, 1.27 1.07-1.50; P < .01), myocardial infarction (OR, 1.34 1.05-1.70; P = .02), and mortality (OR, 2.65 2.06-3.41; P < .01). Minimum SBP <100 mm Hg was associated with MINS (OR, 1.21 1.05-1.39; P = .01) and mortality (OR, 1.81 1.39-2.37; P < .01), but not myocardial infarction (OR, 1.21 0.98-1.49; P = .07). Maximum SBP >160 mm Hg was associated with MINS (OR, 1.16 1.01-1.34; P = .04) and myocardial infarction (OR, 1.34 1.09-1.64; P = .01) but, paradoxically, reduced mortality (OR, 0.76 0.58-0.99; P = .04). Minimum HR <55 bpm was associated with reduced MINS (OR, 0.70 0.59-0.82; P < .01), myocardial infarction (OR, 0.75 0.58-0.97; P = .03), and mortality (OR, 0.58 0.41-0.81; P < .01). Minimum SBP <100 mm Hg with maximum HR >100 bpm was more strongly associated with MINS (OR, 1.42 1.15-1.76; P < .01) compared with minimum SBP <100 mm Hg alone (OR, 1.20 1.03-1.40; P = .02).
Intraoperative tachycardia and hypotension are associated with MINS. Further interventional research targeting HR/blood pressure is needed to define the optimum strategy to reduce MINS.
ObjectiveTo describe outcomes within different ethnic groups of a cohort of hospitalised patients with confirmed COVID-19 infection. To quantify and describe the impact of a number of prognostic ...factors, including frailty and inflammatory markers.SettingFive acute National Health Service Hospitals in east London.DesignProspectively defined observational study using registry data.Participants1737 patients aged 16 years or over admitted to hospital with confirmed COVID-19 infection between 1 January and 13 May 2020.Main outcome measuresThe primary outcome was 30-day mortality from time of first hospital admission with COVID-19 diagnosis during or prior to admission. Secondary outcomes were 90-day mortality, intensive care unit (ICU) admission, ICU and hospital length of stay and type and duration of organ support. Multivariable survival analyses were adjusted for potential confounders.Results1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) black and 707 (40%) white backgrounds. Compared with white patients, those from minority ethnic backgrounds were younger, with differing comorbidity profiles and less frailty. Asian and black patients were more likely to be admitted to ICU and to receive invasive ventilation (OR 1.54, (95% CI 1.06 to 2.23); p=0.023 and OR 1.80 (95% CI 1.20 to 2.71); p=0.005, respectively). After adjustment for age and sex, patients from Asian (HR 1.49 (95% CI 1.19 to 1.86); p<0.001) and black (HR 1.30 (95% CI 1.02 to 1.65); p=0.036) backgrounds were more likely to die. These findings persisted across a range of risk factor-adjusted analyses accounting for major comorbidities, obesity, smoking, frailty and ABO blood group.ConclusionsPatients from Asian and black backgrounds had higher mortality from COVID-19 infection despite controlling for all previously identified confounders and frailty. Higher rates of invasive ventilation indicate greater acute disease severity. Our analyses suggest that patients of Asian and black backgrounds suffered disproportionate rates of premature death from COVID-19.
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.
Small trials suggest that postoperative outcomes may be improved by the use of cardiac output monitoring to guide administration of intravenous fluid and inotropic drugs as part of a hemodynamic ...therapy algorithm.
To evaluate the clinical effectiveness of a perioperative, cardiac output-guided hemodynamic therapy algorithm.
OPTIMISE was a pragmatic, multicenter, randomized, observer-blinded trial of 734 high-risk patients aged 50 years or older undergoing major gastrointestinal surgery at 17 acute care hospitals in the United Kingdom. An updated systematic review and meta-analysis were also conducted including randomized trials published from 1966 to February 2014.
Patients were randomly assigned to a cardiac output-guided hemodynamic therapy algorithm for intravenous fluid and inotrope (dopexamine) infusion during and 6 hours following surgery (n=368) or to usual care (n=366).
The primary outcome was a composite of predefined 30-day moderate or major complications and mortality. Secondary outcomes were morbidity on day 7; infection, critical care-free days, and all-cause mortality at 30 days; all-cause mortality at 180 days; and length of hospital stay.
Baseline patient characteristics, clinical care, and volumes of intravenous fluid were similar between groups. Care was nonadherent to the allocated treatment for less than 10% of patients in each group. The primary outcome occurred in 36.6% of intervention and 43.4% of usual care participants (relative risk RR, 0.84 95% CI, 0.71-1.01; absolute risk reduction, 6.8% 95% CI, -0.3% to 13.9%; P = .07). There was no significant difference between groups for any secondary outcomes. Five intervention patients (1.4%) experienced cardiovascular serious adverse events within 24 hours compared with none in the usual care group. Findings of the meta-analysis of 38 trials, including data from this study, suggest that the intervention is associated with fewer complications (intervention, 488/1548 31.5% vs control, 614/1476 41.6%; RR, 0.77 95% CI, 0.71-0.83) and a nonsignificant reduction in hospital, 28-day, or 30-day mortality (intervention, 159/3215 deaths 4.9% vs control, 206/3160 deaths 6.5%; RR, 0.82 95% CI, 0.67-1.01) and mortality at longest follow-up (intervention, 267/3215 deaths 8.3% vs control, 327/3160 deaths 10.3%; RR, 0.86 95% CI, 0.74-1.00).
In a randomized trial of high-risk patients undergoing major gastrointestinal surgery, use of a cardiac output-guided hemodynamic therapy algorithm compared with usual care did not reduce a composite outcome of complications and 30-day mortality. However, inclusion of these data in an updated meta-analysis indicates that the intervention was associated with a reduction in complication rates.
isrctn.org Identifier: ISRCTN04386758.
Guidelines provide a framework to take better care of our patients. They are published by different professional groups and are based on all the research done for us by hardworking colleagues. ...Compiling a guideline is an enormous amount of work and is generally done with the utmost care. However, recommendations often require a subjective interpretation of published research, where personal and academic interests can influence the outcome. We discuss two recently published guidelines on perioperative cardiovascular assessment that led to different conclusions on some important areas of patient care.
SUMMARY POINTS Non-cardiac surgery has a low overall mortality but is associated with a large number of deaths because so many procedures are performed Most deaths occur in a group of patients who ...are at high risk because of advanced age, comorbid disease, or major surgery (hospital mortality rate 12%) More effective systems can improve quality of perioperative care and may improve survival while reducing healthcare costs Further research is needed to identify the most effective approaches to perioperative medicine for high risk patients Routine audit of outcomes after all non-cardiac surgery is urgently needed
Visual Abstract
BackgroundIncomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded ...by muscle loss and may improve identification of persistent kidney dysfunction.MethodsTo assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation.ResultsLonger length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m2 per day (95% confidence interval CI, 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m2 (95% credible interval CrI, 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R=0.61 (95% CI, 0.50 to 0.72).ConclusionseGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness.Clinical Trial registry name and registration number:Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005.
Latin American countries have a huge diversity in sociocultural factors, ethnicity, geography, and political systems. Provision of healthcare varies widely in Latin America, and it is unclear how ...these disparities relate to outcomes for individual patients undergoing surgery. The Latin American Surgical Outcome Study (LASOS), with its pragmatic design, will provide a snapshot of surgical activity throughout Latin America and identify the next steps needed to improve postoperative outcomes.
Vitamin D deficiency and endothelial dysfunction are non-traditional risk factors for cardiovascular events in chronic kidney disease. Previous studies in chronic kidney disease have failed to ...demonstrate a beneficial effect of vitamin D on arterial stiffness, left ventricular mass and inflammation but none have assessed the effect of vitamin D on microcirculatory endothelial function.
We conducted a randomised controlled trial of 38 patients with non diabetic chronic kidney disease stage 3-4 and concomitant vitamin D deficiency (<16 ng/dl) who received oral ergocalciferol (50,000 IU weekly for one month followed by 50,000 IU monthly) or placebo over 6 months. The primary outcome was change in microcirculatory function measured by laser Doppler flowmetry after iontophoresis of acetylcholine. Secondary endpoints were tissue advanced glycation end products, sublingual functional capillary density and flow index as well as macrovascular parameters. Parallel in vitro experiments were conducted to determine the effect of ergocalciferol on cultured human endothelial cells.
Twenty patients received ergocalciferol and 18 patients received placebo. After 6 months, there was a significant improvement in the ergocalciferol group in both endothelium dependent microcirculatory vasodilatation after iontophoresis of acetylcholine (p = 0.03) and a reduction in tissue advanced glycation end products (p = 0.03). There were no changes in sublingual microcirculatory parameters. Pulse pressure (p = 0.01) but not aortic pulse wave velocity was reduced. There were no significant changes in bone mineral parameters, blood pressure or left ventricular mass index suggesting that ergocalciferol improved endothelial function independently of these parameters. In parallel experiments, expression of endothelial nitric oxide synthase and activity were increased in human endothelial cells in a dose dependent manner.
Ergocalciferol improved microcirculatory endothelial function in patients with chronic kidney disease and concomitant vitamin D deficiency. This process may be mediated through enhanced expression and activity of endothelial nitric oxide synthase.
Clinical trials.gov NCT00882401.
PDF
