Coronavirus disease 2019 (COVID-19) appears to be associated with increased arterial and venous thromboembolic disease. These presumed abnormalities in hemostasis have been associated with filter ...clotting during continuous renal replacement therapy (CRRT). We aimed to characterize the burden of CRRT filter clotting in COVID-19 infection and to describe a CRRT anticoagulation protocol that used anti-factor Xa levels for systemic heparin dosing. Multi-center study of consecutive patients with COVID-19 receiving CRRT. Primary outcome was CRRT filter loss. Sixty-five patients were analyzed, including 17 using an anti-factor Xa protocol to guide systemic heparin dosing. Fifty-four out of 65 patients (83%) lost at least one filter. Median first filter survival time was 6.5 2.5, 33.5 h. There was no difference in first or second filter loss between the anti-Xa protocol and standard of care anticoagulation groups, however fewer patients lost their third filter in the protocolized group (55% vs. 93%) resulting in a longer median third filter survival time (24 15.1, 54.2 vs. 17.3 9.5, 35.1 h, p = 0.04). The rate of CRRT filter loss is high in COVID-19 infection. An anticoagulation protocol using systemic unfractionated heparin, dosed by anti-factor Xa levels is reasonable approach to anticoagulation in this population.
Ziehr et al discuss their retrospective observational cohort study which focused solely on intubated patients with coronavirus disease (COVID-19) respiratory failure at two tertiary medical center. ...It was not a clinical trial and did not include a nonintubated comparator cohort. Dr Yaroshetskiy and colleagues raise important questions about the use of noninvasive respiratory support for COVID-19, but these are questions that their study was not designed to answer.
According to recent European Respiratory Society standards for assessing pulmonary hemodynamics during exercise, all subjects with ePAH had a total pulmonary resistance (mPAP/cardiac output) of >3.0 ...(1) Wood units during exercise while maintaining a PCWP of <20 mm Hg, except for one subject who had a total pulmonary resistance of 2.3 Wood units. Baseline Characteristics Parameter Control (n = 5) ePAH (n = 4) PAH (n = 4) P Value Age, yr 41.2 (22–60) 53.5 (44–62) 47.3 (22–64) 0.52 Sex, F 1 2 3 0.31 Race, white 5 3 3 0.55 Height, cm 170.9 (160–181.6) 169.2 (167.6–180.3) 170.7 (167.6–174) 0.96 Weight, kg 86 (72.6–134.6) 88 (68–107) 77.3 (56.2–119.7) 0.85 Years of symptoms – 4.2 (1–10) 8.4 (7–10) 0.19 FEV1% predicted 103.7 (90–117) 87.9 (76–97) 82.9 (66–95) 0.12 FVC, % predicted 105.8 (100–115) 91.2 (83–118) 85.6 (64–110) 0.24 FEV1/FVC 79 (70–87) 72 (67–89) 80 (63–86) 0.50 mPAP, rest, mm Hg – 18 (15–22) 41.6 (33–63) 0.01 PVR, rest, dyn · s/cm5 – 122.7 (81–143) 442 (322–548) 0.001 PCWP, rest, mm Hg – 9.3 (7–11) 10 (7–16) 0.65 mPAP, exercise, mm Hg – 36 (33–38) – – PVR, exercise, dyn · s/cm5 – 154.6 (136–168) – – PCWP, exercise, mm Hg – 14.3 (11–18) – – 6MWD, m – 485.2 (366–595) 463.2 (382–670) 0.083 Definition of abbreviations: 6MWD = 6-minute-walk distance; ePAH = exercise pulmonary arterial hypertension; mPAP = mean pulmonary arterial pressure; PAH = primary pulmonary arterial hypertension; PCWP = pulmonary capillary wedge pressure; PVR = pulmonary vascular resistance. CV2Q50–70 = squared coefficient of variation in perfusion quantifying the heterogeneity at the length scale of 50–70 mm; ePAH = exercise pulmonary arterial hypertension; O2 +iNO = inhaled nitric oxide with balance gas oxygen; PAH = pulmonary arterial hypertension. ...subjects with ePAH maintained a normal resting vertical gradient in perfusion that was responsive to vasodilation, similar to what was observed in their control counterparts but distinct from subjects with PAH.
Introduction
Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may ...contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.
Objective
To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.
Methods
We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) – the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.
Results
Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes
N
-formyl-
l
-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and
N
-lactoyl-phenylalanine (lac-Phe), representative of the
N
-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.
Conclusion
Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.
Ziehr et al respond to a commentary on their article on the standards and stereotypes of COVID-19. Massachusetts General Hospital and Beth Israel Deaconess Medical Center are tertiary care hospitals ...at the epicenter of the COVID-19 response in Boston MA. As of May 16, 2020, the hospitals have cared for more than 700 critically ill patients with COVID-19. Our motivation to publish our frontline systematic observations stemmed from concern that anecdotal reports, susceptible to cognitive biases, were gaining significant attention and impacting practice patterns for respiratory failure. They comment that frontline experience remains critical to inform real-time patient care and shape future research. They urge the continued rigorous study of these observations to accurately inform the management of critically ill patients with COVID-19.
Prone positioning improves clinical outcomes in moderate-to-severe acute respiratory distress syndrome and has been widely adopted for the treatment of patients with acute respiratory distress ...syndrome due to coronavirus disease 2019. Little is known about the effects of prone positioning among patients with less severe acute respiratory distress syndrome, obesity, or those treated with pulmonary vasodilators.
We characterize the change in oxygenation, respiratory system compliance, and dead-space-to-tidal-volume ratio in response to prone positioning in patients with coronavirus disease 2019 acute respiratory distress syndrome with a range of severities. A subset analysis of patients treated with inhaled nitric oxide and subsequent prone positioning explored the influence of pulmonary vasodilation on the physiology of prone positioning.
Retrospective cohort study of all consecutively admitted adult patients with acute respiratory distress syndrome due to coronavirus disease 2019 treated with mechanical ventilation and prone positioning in the ICUs of an academic hospital between March 11, 2020, and May 1, 2020.
Respiratory system mechanics and gas exchange during the first episode of prone positioning.
Among 122 patients, median (interquartile range) age was 60 years (51-71 yr), median body mass index was 31.5 kg/m
(27-35 kg/m
), and 50 patients (41%) were female. The ratio of Pao
to Fio
improved with prone positioning in 90% of patients. Prone positioning was associated with a significant increase in the ratio of Pao
to Fio
(from median 149 123-170 to 226 169-268,
< 0.001) but no change in dead-space-to-tidal-volume ratio or respiratory system compliance. Supine ratio of Pao
to Fio
, respiratory system compliance, positive end-expiratory pressure, and body mass index did not correlate with absolute change in the ratio of Pao
to Fio
with prone positioning. However, patients with ratio of Pao
to Fio
less than 150 experienced a greater relative improvement in oxygenation with prone positioning than patients with ratio of Pao
to Fio
greater than or equal to 150 (median percent change in ratio of Pao
to Fio
62 29-107 vs 30 10-70,
= 0.002). Among 12 patients, inhaled nitric oxide prior to prone positioning was associated with a significant increase in the ratio of Pao
to Fio
(from median 136 77-168 to 170 138-213,
= 0.003) and decrease in dead-space-to-tidal-volume ratio (0.54 0.49-0.58 to 0.46 0.44-0.53,
= 0.001). Subsequent prone positioning in this subgroup further improved the ratio of Pao
to Fio
(from 145 122-183 to 205 150-232,
= 0.017) but did not change dead-space-to-tidal-volume ratio.
Prone positioning improves oxygenation across the acute respiratory distress syndrome severity spectrum, irrespective of supine respiratory system compliance, positive end-expiratory pressure, or body mass index. There was a greater relative benefit among patients with more severe disease. Prone positioning confers an additive benefit in oxygenation among patients treated with inhaled nitric oxide.
Soluble suppression of tumorigenicity-2 and interleukin-6 concentrations have been associated with the inflammatory cascade of acute respiratory distress syndrome. We determined whether soluble ...suppression of tumorigenicity-2 and interleukin-6 levels can be used as prognostic biomarkers to guide weaning from mechanical ventilation and predict the need for reintubation.
We assayed plasma soluble suppression of tumorigenicity-2 (n = 826) concentrations and interleukin-6 (n = 755) concentrations in the Fluid and Catheter Treatment Trial, a multicenter randomized controlled trial of conservative fluid management in acute respiratory distress syndrome. We tested whether soluble suppression of tumorigenicity-2 and interleukin-6 levels were associated with duration of mechanical ventilation, the probability of passing a weaning assessment, and the need for reintubation.
In models adjusted for Acute Physiology and Chronic Health Evaluation score and other relevant variables, patients with higher day 0 and day 3 median soluble suppression of tumorigenicity-2 and interleukin-6 concentrations had decreased probability of extubation over time (day 0 soluble suppression of tumorigenicity-2: hazard ratio, 0.85; 95% CI, 0.72-1.00; p = 0.05; day 0 interleukin-6: hazard ratio, 0.64; 95% CI, 0.54-0.75; p < 0.0001; day 3 soluble suppression of tumorigenicity-2: hazard ratio, 0.64; 95% CI, 0.54-0.75; p < 0.0001; and day 3 interleukin-6: hazard ratio, 0.73; 95% CI, 0.62-0.85; p = 0.0001). Higher biomarker concentrations were also predictive of decreased odds of passing day 3 weaning assessments (soluble suppression of tumorigenicity-2: odds ratio, 0.62: 95% CI, 0.44-0.87; p = 0.006 and interleukin-6: odds ratio, 0.61; 95% CI, 0.43-0.85; p = 0.004) and decreased odds of passing a spontaneous breathing trial (soluble suppression of tumorigenicity-2: odds ratio, 0.45; 95% CI, 0.28-0.71; p = 0.0007 and interleukin-6 univariate analysis only: odds ratio, 0.55; 95% CI, 0.36-0.83; p = 0.005). Finally, higher biomarker levels were significant predictors of the need for reintubation for soluble suppression of tumorigenicity-2 (odds ratio, 3.23; 95% CI, 1.04-10.07; p = 0.04) and for interleukin-6 (odds ratio, 2.58; 95% CI, 1.14-5.84; p = 0.02).
Higher soluble suppression of tumorigenicity-2 and interleukin-6 concentrations are each associated with worse outcomes during weaning of mechanical ventilation and increased need for reintubation in patients with acute respiratory distress syndrome. Biomarker-directed ventilator management may lead to improved outcomes in weaning of mechanical ventilation in patients with acute respiratory distress syndrome.
Code status orders impact clinical outcomes as well as patients’ and surrogates’ experiences. This is the first multicenter cohort examining code status orders of ICU patients with COVID-19 reported ...to date.
This is a retrospective cohort study including adult patients who tested positive for SARS-CoV-2 and were admitted to the ICU at three hospitals in Massachusetts from March 11, 2020 - May 31, 2020. We examined differences in code status orders at multiple timepoints and performed multivariable regression analysis to identify variables associated with code status at admission.
Among 459 ICU patients with COVID-19, 421 (91.7%) were Full Code at hospital admission. Age and admission from a facility were positively associated with DNR status (adjusted OR 1.10, 95% CI 1.05–1.15, p < 0.001 and adjusted OR 2.68, CI 1.23–5.71, p = 0.011, respectively) while non-English preferred language was negatively associated with DNR status (adjusted OR 0.29, 95% CI 0.10–0.74, p = 0.012). Among 147 patients who died during hospitalization, 95.2% (140) died with DNR code status; most (86.4%) died within two days of final code status change.
The association of non-English preferred language with Full Code status in critically ill COVID-19 patients highlights the importance of medical interpreters in the ICU. Patients who died were transitioned to DNR more than in previous studies, possibly reflecting changes in practice during a novel pandemic.
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•PMETAC grafted from PPV and PPE macroinitiators.•Long (HMW) and short (LMW) METAC grafts were added.•These polymers have greatly amplified charge versus previous PPEs.•Graft ...copolymers exhibited potent antibacterial activity.•PPE-g-PMETAC (LMW) exhibited the greatest antimicrobial activity.
Antimicrobial resistance is becoming a global health concern; as such, the need for new effective treatments and preventive measures is increasing. Poly(para-phenylene ethynylene) (PPE)- and poly(para-phenylene vinylene) (PPV)-poly(2-(methacryloyloxy)ethyl) trimethylammonium chloride (PMETAC) graft copolymers were tested against a range of clinically and industrially relevant bacteria and results showed many of these conjugated polyelectrolytes (CPE’s) to be active. Of all of the compounds tested, PPE-g-PMETAC (low molecular weight, LMW) had greatest antimicrobial activity, especially against Enterococcus faecium, Methicillin resistant Staphylococcus aureus (MRSA), Escherichia coli and Acinetobacter baumannii.
Severely broken bones often require external bone fixation pins to provide support but they can become infected. In order to reduce such infections, novel solutions are required. Titanium zirconium ...nitride (Ti-ZrN) and Ti-ZrN silver (Ti-ZrN/Ag) coatings were deposited onto stainless steel. Surface microtopography demonstrated that on the silver containing surfaces, S
and S
values demonstrated similar trends whilst the R
, average height and RMS value and S
values increased with increasing silver concentration. On the Ti-ZrN/Ag coatings, surface hydrophobicity followed the same trend as the S
and S
values. An increase in dead Staphylococcus aureus and Staphylococcus epidermidis cells was observed on the coatings with a higher silver concentration. Using CTC staining, a significant increase in S. aureus respiration on the silver containing surfaces was observed in comparison to the stainless steel control whilst against S. epidermidis, no significant difference in viable cells was observed across the surfaces. Cytotoxicity testing revealed that the TiZrN coatings, both with and without varying silver concentrations, did not possess a detrimental effect to a human monocyte cell line U937. This work demonstrated that such coatings have the potential to reduce the viability of bacteria that result in pin tract infections.
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