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Early Enteral Nutrition in Mechanically Ventilated Patients With COVID-19 Infection.
Farina, N, Nordbeck, S, Montgomery, M, Cordwin, L, Blair, F, Cherry-Bukowiec, J, Kraft, MD, Pleva, MR, Raymond, E
Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. 2021;(2):440-448
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Abstract
BACKGROUND Nutrition therapy is essential in critically ill adults. Little is known about appropriate nutrition therapy in patients with severe coronavirus disease 2019 (COVID-19) infection. METHODS This was a retrospective, observational study in adult patients with confirmed COVID-19 infection receiving mechanical ventilation. Data regarding patient demographics and nutrition therapy were collected. Patients that received enteral nutrition within 24 hours of starting mechanical ventilation were compared with patients starting enteral nutrition later. The primary outcome was inpatient length of stay. Propensity score matching was conducted to control for baseline differences in patient groups. RESULTS One hundred fifty-five patients were included in final analysis. Patients who received enteral nutrition within 24 hours received a significantly greater daily amount of calories (17.5 vs 15.2 kcal/kg, P = .015) and protein (1.04 vs 0.85 g/kg, P = .003). There was no difference in length of stay (18.5 vs 23.5 days, P = .37). The propensity score analysis included 100 patients. Following propensity scoring, significant differences in daily calorie (17.7 [4.6] vs 15.1 [5.1] kcal/kg/d, P = .009) and protein (1.03 [0.35] vs 0.86 [0.38] g/kg/d, P = .014) provision remained. No differences in length of stay or other outcomes were noted in the propensity score analysis. CONCLUSION Initiation of enteral nutrition within 24 hours was not associated with improved outcomes in mechanically ventilated adults with COVID-19. No harm was detected either. Future research should seek to clarify optimal timing of enteral nutrition initiation in patients with COVID-19 who require mechanical ventilation.
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Nebulised heparin for patients with or at risk of acute respiratory distress syndrome: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.
Dixon, B, Smith, RJ, Campbell, DJ, Moran, JL, Doig, GS, Rechnitzer, T, MacIsaac, CM, Simpson, N, van Haren, FMP, Ghosh, AN, et al
The Lancet. Respiratory medicine. 2021;(4):360-372
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BACKGROUND Mechanical ventilation in intensive care for 48 h or longer is associated with the acute respiratory distress syndrome (ARDS), which might be present at the time ventilatory support is instituted or develop afterwards, predominantly during the first 5 days. Survivors of prolonged mechanical ventilation and ARDS are at risk of considerably impaired physical function that can persist for years. An early pathogenic mechanism of lung injury in mechanically ventilated, critically ill patients is inflammation-induced pulmonary fibrin deposition, leading to thrombosis of the microvasculature and hyaline membrane formation in the air sacs. The main aim of this study was to determine if nebulised heparin, which targets fibrin deposition, would limit lung injury and thereby accelerate recovery of physical function in patients with or at risk of ARDS. METHODS The Can Heparin Administration Reduce Lung Injury (CHARLI) study was an investigator-initiated, multicentre, double-blind, randomised phase 3 trial across nine hospitals in Australia. Adult intensive care patients on invasive ventilation, with impaired oxygenation defined by a PaO2/FiO2 ratio of less than 300, and with the expectation of invasive ventilation beyond the next calendar day were recruited. Key exclusion criteria were heparin allergy, pulmonary bleeding, and platelet count less than 50 X 109/L. Patients were randomly assigned 1:1, with stratification by site and using blocks of variable size and random seed, via a web-based system, to either unfractionated heparin sodium 25 000 IU in 5 mL or identical placebo (sodium chloride 0·9% 5 mL), administered using a vibrating mesh membrane nebuliser every 6 h to day 10 while invasively ventilated. Patients, clinicians, and investigators were masked to treatment allocation. The primary outcome was the Short Form 36 Health Survey Physical Function Score (out of 100) of survivors at day 60. Prespecified secondary outcomes, which are exploratory, included development of ARDS to day 5 among at-risk patients, deterioration of the Murray Lung Injury Score (MLIS) to day 5, mortality at day 60, residence of survivors at day 60, and serious adverse events. Analyses followed the intention-to-treat principle. There was no imputation of missing data. The trial is registered with the Australian and New Zealand Clinical Trials Register, number ACTRN12612000418875 . FINDINGS Between Sept 4, 2012, and Aug 23, 2018, 256 patients were randomised. Final follow-up was on Feb 25, 2019. We excluded three patients who revoked consent and one ineligible participant who received no intervention. Of 252 patients included in data analysis, the mean age was 58 years (SD 15), 157 (62%) were men, and 118 (47%) had ARDS. 128 (51%) patients were assigned to the heparin group and 124 (49%) to the placebo group, all of whom received their assigned intervention. Survivors in the heparin group (n=97) had similar SF-36 Physical Function Scores at day 60 compared to the placebo group (n=94; mean 53·6 [SD 31·6] vs 48·7 [35·7]; difference 4·9 [95% CI -4·8 to 14·5]; p=0·32). Compared with the placebo group, the heparin group had fewer cases of ARDS develop to day 5 among the at-risk patients (nine [15%] of 62 patients vs 21 [30%] of 71 patients; hazard ratio 0·46 [95% CI 0·22 to 0·98]; p=0·0431), less deterioration of the MLIS to day 5 (difference -0·14 [-0·26 to -0·02]; p=0·0215), similar day 60 mortality (23 [18%] of 127 patients vs 18 [15%] of 123 patients; odds ratio [OR] 1·29 [95% CI 0·66 to 2·53]; p=0·46), and more day 60 survivors at home (86 [87%] of 99 patients vs 73 [73%] of 100 patients; OR 2·45 [1·18 to 5·08]; p=0·0165). A similar number of serious adverse events occurred in each group (seven [5%] of 128 patients in the heparin group vs three [2%] of 124 patients in the placebo group; OR 2·33 [0·59 to 9·24]; p=0·23), which were a transient increase in airway pressure during nebulisation (n=3 in the heparin group), major non-pulmonary bleeding (n=2 in each group), haemoptysis (n=1 in the heparin group), tracheotomy site bleeding (n=1 in the heparin group), and hypoxaemia during nebulisation (n=1 in the placebo group). INTERPRETATION In patients with or at risk of ARDS, nebulised heparin did not improve self-reported performance of daily physical activities, but was well tolerated and exploratory outcomes suggest less progression of lung injury and earlier return home. Further research is justified to establish if nebulised heparin accelerates recovery in those who have or are at risk of ARDS. FUNDING Rowe Family Foundation, TR and RB Ditchfield Medical Research Endowment Fund, Patricia Madigan Charitable Trust, and The J and R McGauran Trust Fund.
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Oropharyngeal colostrum therapy reduces the incidence of ventilator-associated pneumonia in very low birth weight infants: a systematic review and meta-analysis.
Ma, A, Yang, J, Li, Y, Zhang, X, Kang, Y
Pediatric research. 2021;(1):54-62
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BACKGROUND Oropharyngeal colostrum (OC) is a novel feeding strategy to prevent complications of prematurity. A meta-analysis was conducted to investigate whether very low birth weight infants (VLBWs) can benefit from OC. METHODS Randomized controlled trials (RCTs) were searched from Embase, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials from the date of inception until May 2019. RCTs were eligible if they used OC therapy on VLBW infants. The primary outcomes included ventilator-associated pneumonia (VAP), necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD), late-onset sepsis, and death. The secondary outcomes included the time of full enteral feeding and the length of stay. RESULTS Eight RCTs involving 682 patients (OC group: 332; non-OC group: 350) were included in the meta-analysis. The results suggested that OC was associated with a significantly reduced incidence of VAP [odds ratio (OR) = 0.39, 95% confidence interval (CI): 0.17-0.88, P = 0.02] and full enteral feeding days (mean difference = -2.66, 95% CI: -4.51 to -0.80, P = 0.005), a potential significance of NEC (OR = 0.51, 95% CI: 0.26-0.99, P = 0.05), a trend toward downregulating mortality (OR = 0.60, 95% CI: 0.34-1.08, P = 0.09) and proven sepsis (OR = 0.64, 95% CI: 0.40-1.01, P = 0.06). CONCLUSIONS OC could significantly reduce the occurrence of VAP, and consequently, its routine use should be considered for VLBWs to prevent infectious diseases. IMPACT OC significantly reduces the occurrence of VAP and NEC in VLBW infants. OC may reduce the incidence of VAP and NEC by increasing IgA levels. Early OC therapy for mechanical ventilation of low-weight infants may prevent the occurrence of VAP.
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Energy requirements of long-term ventilated COVID-19 patients with resolved SARS-CoV-2 infection.
von Renesse, J, von Bonin, S, Held, HC, Schneider, R, Seifert, AM, Seifert, L, Spieth, P, Weitz, J, Welsch, T, Meisterfeld, R
Clinical nutrition ESPEN. 2021;:211-217
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BACKGROUND & AIMS Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can rapidly progress into acute respiratory distress syndrome accompanied by multi-organ failure requiring invasive mechanical ventilation and critical care treatment. Nutritional therapy is a fundamental pillar in the management of hospitalized patients. It is broadly acknowledged that overfeeding and underfeeding of intensive care unit (ICU) patients are associated with increased morbidity and mortality. This study aimed to assess the energy demands of long-term ventilated COVID-19 patients using indirect calorimetry and to evaluate the applicability of established predictive equations to estimate their energy expenditure. METHODS We performed a retrospective, single-center study in 26 mechanically ventilated COVID-19 patients with resolved SARS-CoV-2 infection in three independent intensive care units. Resting energy expenditure (REE) was evaluated by repetitive indirect calorimetry (IC) measurements. Simultaneously the performance of 12 predictive equations was examined. Patient's clinical data were retrieved from electronic medical charts. Bland-Altman plots were used to assess agreement between measured and calculated REE. RESULTS Mean mREE was 1687 kcal/day and 20.0 kcal relative to actual body weight (ABW) per day (kcal/kg/day). Longitudinal mean mREE did not change significantly over time, although mREE values had a high dispersion (SD of mREE ±487). Obese individuals were found to have significantly increased mREE, but lower energy expenditure relative to their body mass. Calculated REE showed poor agreement with mREE ranging from 33 to 54%. CONCLUSION Resolution of SARS-CoV-2 infection confirmed by negative PCR leads to stabilization of energy demands at an average 20 kcal/kg in ventilated critically ill patients. Due to high variations in mREE and low agreement with calculated energy expenditure IC remains the gold standard for the guidance of nutritional therapy.
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Acute Respiratory Distress Syndrome: Diagnosis and Management.
Saguil, A, Fargo, MV
American family physician. 2020;(12):730-738
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Acute respiratory distress syndrome (ARDS) is noncardiogenic pulmonary edema that manifests as rapidly progressive dyspnea, tachypnea, and hypoxemia. Diagnostic criteria include onset within one week of a known insult or new or worsening respiratory symptoms, profound hypoxemia, bilateral pulmonary opacities on radiography, and inability to explain respiratory failure by cardiac failure or fluid overload. ARDS is thought to occur when a pulmonary or extrapulmonary insult causes the release of inflammatory mediators, promoting inflammatory cell accumulation in the alveoli and microcirculation of the lung. Inflammatory cells damage the vascular endothelium and alveolar epithelium, leading to pulmonary edema, hyaline membrane formation, decreased lung compliance, and decreased gas exchange. Most cases are associated with pneumonia or sepsis. ARDS is responsible for one in 10 admissions to intensive care units and one in four mechanical ventilations. In-hospital mortality for patients with severe ARDS ranges from 46% to 60%. ARDS often must be differentiated from pneumonia and congestive heart failure, which typically has signs of fluid overload. Treatment of ARDS is supportive and includes mechanical ventilation, prophylaxis for stress ulcers and venous thromboembolism, nutritional support, and treatment of the underlying injury. Low tidal volume and high positive end-expiratory pressure improve outcomes. Prone positioning is recommended for some moderate and all severe cases. As patients with ARDS improve and the underlying illness resolves, a spontaneous breathing trial is indicated to assess eligibility for ventilator weaning. Patients who survive ARDS are at risk of diminished functional capacity, mental illness, and decreased quality of life; ongoing care by a primary care physician is beneficial for these patients.
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Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study.
Pérez-Belmonte, LM, Torres-Peña, JD, López-Carmona, MD, Ayala-Gutiérrez, MM, Fuentes-Jiménez, F, Jorge Huerta, L, Muñoz, JA, Rubio-Rivas, M, Madrazo, M, Garcia, MG, et al
BMC medicine. 2020;(1):359
Abstract
BACKGROUND Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.
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Randomised controlled trial to investigate the relationship between mild hypercapnia and cerebral oxygen saturation in patients undergoing major surgery.
Wong, C, Churilov, L, Cowie, D, Tan, CO, Hu, R, Tremewen, D, Pearce, B, Pillai, P, Karalapillai, D, Bellomo, R, et al
BMJ open. 2020;(2):e029159
Abstract
OBJECTIVES The effects of hypercapnia on regional cerebral oxygen saturation (rSO2) during surgery are unclear. We conducted a randomised controlled trial to investigate the relationship between mild hypercapnia and rSO2. We hypothesised that, compared with targeted normocapnia (TN), targeted mild hypercapnia (TMH) during major surgery would increase rSO2. DESIGN A prospective, randomised, controlled trial in adult participants undergoing elective major surgery. SETTING A single tertiary centre in Heidelberg, Victoria, Australia. PARTICIPANTS 40 participants were randomised to either a TMH or TN group (20 to each). INTERVENTIONS TMH (partial pressure of carbon dioxide in arterial blood, PaCO2, 45-55 mm Hg) or TN (PaCO2 35-40 mm Hg) was delivered via controlled ventilation throughout surgery. PRIMARY AND SECONDARY OUTCOME MEASURES The primary endpoint was the absolute difference between the two groups in percentage change in rSO2 from baseline to completion of surgery. Secondary endpoints included intraoperative pH, bicarbonate concentration, base excess, serum potassium concentration, incidence of postoperative delirium and length of stay (LOS) in hospital. RESULTS The absolute difference between the two groups in percentage change in rSO2 from the baseline to the completion of surgery was 19.0% higher in both hemispheres with TMH (p<0.001). On both sides, the percentage change in rSO2 was greater in the TMH group than the TN group throughout the duration of surgery. The difference between the groups became more noticeable over time. Furthermore, postoperative delirium was higher in the TN group (risk difference 0.3, 95% CI 0.1 to 0.5, p=0.02). LOS was similar between groups (5 days vs 5 days; p=0.99). CONCLUSION TMH was associated with a stable increase in rSO2 from the baseline, while TN was associated with a decrease in rSO2 in both hemispheres in patients undergoing major surgery. This resulted in a clear separation of percentage change in rSO2 from the baseline between TMH and TN over time. Our findings provide the rationale for larger studies on TMH during surgery. TRIAL REGISTRATION NUMBER The Australian New Zealand Clinical Trials Registry (ACTRN12616000320459).
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Beyond ventilatory support: challenges in general practice and in the treatment of critically Ill children and adolescents with SARS-CoV-2 infection.
Ferranti, JF, Rodriguez, IS, Motta, E, Johnston, C, Carvalho, WBB, Delgado, AF
Revista da Associacao Medica Brasileira (1992). 2020;(4):521-527
Abstract
Severe acute respiratory syndrome coronavirus 2 (Sars-CoV-2 infection) is a new challenge for all countries, and children are predisposed to acquire this disease. Some studies have demonstrated more severe diseases in adults, but critically ill pediatric patients have been described in all ages. Pulmonary involvement is the major feature, and ventilatory support is common in critical cases. Nevertheless, other very important therapeutic approaches must be considered. In this article, we reviewed extensively all recent medical literature to point out the main clinical attitudes to support these pediatric patients during their period in respiratory support. Radiologic findings, fluid therapy, hemodynamic support, use of inotropic/vasopressors, nutritional therapy, antiviral therapy, corticosteroids, antithrombotic therapy, and immunoglobulins are analyzed to guide all professionals during hospitalization. We emphasize the importance of a multi-professional approach for adequate recovery.
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Fluid overload after coronary artery bypass graft in patients on maintenance hemodialysis is associated with prolonged time on mechanical ventilation.
da Silva, SC, Consolim-Colombo, FM, Rodrigues, RG, Gaiotto, FA, Hajjar, LA, Moysés, RMA, Elias, RM
BMC anesthesiology. 2020;(1):60
Abstract
BACKGROUND Fluid overload is a risk factor for morbidity, mortality, and prolonged ventilation time after surgery. Patients on maintenance hemodialysis might be at higher risk. We hypothesized that fluid accumulation would be directly associated with extended ventilation time in patients on hemodialysis, as compared to patients with chronic kidney disease not on dialysis (CKD3-4) and patients with normal renal function (reference group). METHODS This is a prospective observational study that included patients submitted to isolated and elective coronary artery bypass surgery, divided in 3 groups according to time on mechanical ventilation: < 24 h, 24-48 h and > 48 h. The same observer followed patients daily from the surgery to the hospital discharge. Cumulative fluid balance was defined as the sum of daily fluid balance over the first 5 days following surgery. RESULTS Patients requiring more than 48 h of ventilation (5.3%) had a lower estimated glomerular filtration rate, were more likely to be on maintenance dialysis, had longer anesthesia time, needed higher dobutamine and noradrenaline infusion following surgery, and had longer hospitalization stay. Multivariate analysis revealed that the fluid accumulation, scores of sequential organ failure assessment in the day following surgery, and the renal function (normal, chronic kidney disease not on dialysis and maintenance hemodialysis) were independently associated with time in mechanical ventilation. Among patients on hemodialysis, the time from the surgery to the first hemodialysis session also accounted for the time on mechanical ventilation. CONCLUSIONS Fluid accumulation is an important risk factor for lengthening mechanical ventilation, particularly in patients on hemodialysis. Future studies are warranted to address the ideal timing for initiating dialysis in this scenario in an attempt to reduce fluid accumulation and avoid prolonged ventilation time and hospital stay.
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Intensity of Renal Replacement Therapy and Duration of Mechanical Ventilation: Secondary Analysis of the Acute Renal Failure Trial Network Study.
Sharma, S, Kelly, YP, Palevsky, PM, Waikar, SS
Chest. 2020;(4):1473-1481
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BACKGROUND Randomized clinical trials have failed to show benefit from increasing intensity of renal replacement therapy (RRT) for acute kidney injury, but continue to be frequently used. In addition, intensive RRT is associated with an increase in adverse events potentially secondary to small solute losses, such as phosphate. We hypothesized that, compared with less-intensive RRT, intensive RRT would lead to longer duration of mechanical ventilation. RESEARCH QUESTION Does more-intensive renal replacement therapy in critically ill patients with acute kidney injury increase time to extubation from mechanical ventilation when compared with less-intensive therapy? STUDY DESIGN AND METHODS The Acute Renal Failure Trial Network study was a randomized multicenter trial of more-intensive (hemodialysis or sustained low-efficiency dialysis six times per week or continuous venovenous hemodiafiltration at 35 mL/kg per hour) vs less-intensive (hemodialysis or sustained low-efficiency dialysis three times per week or continuous venovenous hemodiafiltration at 20 mL/kg per hour) RRT in critically ill patients with acute kidney injury. Of 1124 patients, 907 who were supported by mechanical ventilation on study initiation were included in this Cox-proportional hazards analysis. The primary outcome was the time to first successful extubation off mechanical ventilation. RESULTS Patients who were assigned randomly to more-intensive RRT had a 33.3% lower hazard rate of successful extubation (hazard ratio, 0.67; 95% CI, 0.52-0.88; P < .001) when compared with patients who were assigned to less-intensive RRT. Patients who were assigned to more-intensive RRT had, on average, 2.07 ventilator-free days, compared with 3.08 days in those who were assigned to less-intensive RRT (P < .001) over 14 days from start of the study. INTERPRETATION Critically ill mechanically ventilated patients who were assigned randomly to more-intensive RRT had longer duration of mechanical ventilation compared with those who were assigned to less-intensive RRT. The reasons for this, such as excessive phosphate loss from more-intensive RRT, deserve further study to optimize the safety and effectiveness of CRRT delivery. This was a post hoc analysis of the Acute Renal Failure Trial Network study; clinical trial registration of the original trial is NCT00076219.