scholarly journals Standard- versus intermediate-dose enoxaparin for anti-factor Xa guided thromboprophylaxis in critically ill patients with COVID-19

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
David Oliver Hamilton ◽  
Alexander Main-Ian ◽  
Jessie Tebbutt ◽  
Maya Thrasher ◽  
Alicia Waite ◽  
...  

AbstractThe prevalence of venous thromboembolism (VTE) is high in critically ill patients with COVID-19. Dosing of Low Molecular Weight Heparin (LMWH) for thromboprophylaxis in patients with severe COVID-19 is subject to ongoing debate.In this brief report, we describe our study where we retrospectively examined the efficacy of standard- versus intermediate-dosing of enoxaparin in attaining and maintaining accepted prophylactic levels of anti-Factor Xa (anti-FXa) in critically ill patients with COVID-19.We collected data for all patients with confirmed COVID-19 who were treated with enoxaparin for thromboprophylaxis in a single Intensive Care Unit (ICU) in the United Kingdom between 31st March and 16th November 2020. Standard-dose of enoxaparin was 40 mg subcutaneously once daily for patients with normal renal function and body weight between 50 and 100 kg; the intermediate-dose was 40 mg subcutaneously twice daily. Anti-FXa peak concentrations between 0.2-0.4 IU/ml were considered appropriate for thromboprophylaxis.Age, sex, weight, Body Mass Index, APACHE II score, ICU length of stay, initial P/F ratio and creatinine were not statistically significantly different between standard- and intermediate-dose thromboprophylaxis cohorts. In the standard-dose group, the median initial anti-FXa level was 0.13 (interquartile range 0.06-0.18) compared to 0.26 (0.21-0.33) in the intermediate-dose cohort (p < 0.001). On repeated measurement, in the standard dose cohort, 44 of 95 (46%) anti-FXa levels were < 0.2 IU/ml compared with 24 of 132 (18%) levels in the intermediate-dose cohort even after dose-adjustment. There was one radiologically confirmed pulmonary embolism (PE) on computed tomography pulmonary angiogram during hospital admission in each cohort.Our study supports starting intermediate-dose thromboprophylaxis for critically ill patients with COVID-19 to achieve anti-FXa levels in the accepted thromboprophylactic range although further study is required to investigate whether anti-FXa guided thromboprophylaxis is safe and effective in reducing the incidence of VTEs in critically ill patients with COVID-19.

2016 ◽  
Vol 32 (10) ◽  
pp. 574-577 ◽  
Author(s):  
Zachary R. Noel ◽  
Melissa L. Thompson Bastin ◽  
Ashley A. Montgomery ◽  
Alexander H. Flannery

Background: Limited data support high-dose oseltamivir in critically ill patients with influenza. In several recent influenza seasons, there were oseltamivir drug shortages. Methods: This was a retrospective cohort analysis of 57 patients admitted to the intensive care unit (ICU) with confirmed influenza. Patients receiving high-dose oseltamivir were compared to those receiving standard dosing. Results: When adjusted for clinically relevant predictors of disease severity, including age, duration of therapy, Acute Physiology and Chronic Health Evaluation II score, and receipt of extracorporeal membrane oxygenation, there was no difference in the duration of mechanical ventilation, oxygenation, ICU length of stay, or hospital length of stay between the high-dose and standard dose groups. Conclusions: As compared to the standard doses of oseltamivir, higher-dose (ie, double dose) oseltamivir was not associated with improvement in any clinical outcomes. Using higher doses empirically on all patients during influenza season may exacerbate local drug shortages.


Author(s):  
Răzvan Bologheanu ◽  
Mathias Maleczek ◽  
Daniel Laxar ◽  
Oliver Kimberger

Summary Background Coronavirus disease 2019 (COVID-19) disrupts routine care and alters treatment pathways in every medical specialty, including intensive care medicine, which has been at the core of the pandemic response. The impact of the pandemic is inevitably not limited to patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and their outcomes; however, the impact of COVID-19 on intensive care has not yet been analyzed. Methods The objective of this propensity score-matched study was to compare the clinical outcomes of non-COVID-19 critically ill patients with the outcomes of prepandemic patients. Critically ill, non-COVID-19 patients admitted to the intensive care unit (ICU) during the first wave of the pandemic were matched with patients admitted in the previous year. Mortality, length of stay, and rate of readmission were compared between the two groups after matching. Results A total of 211 critically ill SARS-CoV‑2 negative patients admitted between 13 March 2020 and 16 May 2020 were matched to 211 controls, selected from a matching pool of 1421 eligible patients admitted to the ICU in 2019. After matching, the outcomes were not significantly different between the two groups: ICU mortality was 5.2% in 2019 and 8.5% in 2020, p = 0.248, while intrahospital mortality was 10.9% in 2019 and 14.2% in 2020, p = 0.378. The median ICU length of stay was similar in 2019: 4 days (IQR 2–6) compared to 2020: 4 days (IQR 2–7), p = 0.196. The rate of ICU readmission was 15.6% in 2019 and 10.9% in 2020, p = 0.344. Conclusion In this retrospective single center study, mortality, ICU length of stay, and rate of ICU readmission did not differ significantly between patients admitted to the ICU during the implementation of hospital-wide COVID-19 contingency planning and patients admitted to the ICU before the pandemic.


Pharmaceutics ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 54 ◽  
Author(s):  
Amaia Soraluce ◽  
Helena Barrasa ◽  
Eduardo Asín-Prieto ◽  
Jose Ángel Sánchez-Izquierdo ◽  
Javier Maynar ◽  
...  

Antimicrobial treatment in critically ill patients remains challenging. The aim of this study was to develop a population pharmacokinetic model for linezolid in critically ill patients and to evaluate the adequacy of current dosing recommendation (600 mg/12 h). Forty inpatients were included, 23 of whom were subjected to continuous renal replacement therapies (CRRT). Blood and effluent samples were drawn after linezolid administration at defined time points, and linezolid levels were measured. A population pharmacokinetic model was developed, using NONMEM 7.3. The percentage of patients that achieved the pharmacokinetic/pharmacodynamic (PK/PD) targets was calculated (AUC24/MIC > 80 and 100% T>MIC). A two-compartment model best described the pharmacokinetics of linezolid. Elimination was conditioned by the creatinine clearance and by the extra-corporeal clearance if the patient was subjected to CRRT. For most patients, the standard dose of linezolid did not cover infections caused by pathogens with MIC ≥ 2 mg/L. Continuous infusion may be an alternative, especially when renal function is preserved.


2021 ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Alaa Alhubaishi ◽  
Ohoud Al Juhani ◽  
Khalid Eljaaly ◽  
Omar Al Harbi ◽  
...  

Abstract Background: Corticosteroids, especially dexamethasone, showed a survival benefit in critically ill COVID 19 patients. However, it is unclear whether the timing of dexamethasone initiation is associated with positive outcomes. The aim of this study is to evaluate the timing of dexamethasone initiation and 30-day ICU mortality in critically ill patients with COVID19. Methods: A multicenter, non-interventional, prospective study for all adult COVID19 admitted to intensive care units (ICUs) who received systemic dexamethasone between March 01 to December 31, 2020. Patients were divided into two groups based on the timing for dexamethasone initiation (early vs. late). Early use defined as the initiation of dexamethasone within three days of ICU admission. Multivariate logistic and generalized linear regression were used. We considered a P value of < 0.05 statistically significant. Results: A total of 475 patients were included in the study; dexamethasone was initiated early within three days of ICU admission in 433 patients. Early initiation of dexamethasone was associated with lower 30-day ICU mortality (OR [95%CI]: 0.43 [0.23, 0.81], p-value = 0.01), and acute kidney injury during ICU stay, (OR [95%CI]: 0.45 [0.21, 0.94], p-value = 0.03). Additionally, among survivors, early initiation was associated with shorter MV duration (beta coefficient [95% CI]: -0.94 [-1.477, -0.395], p-value = 0.0001), ICU length of stay (LOS) (beta coefficient [95%CI]: -0.73 [-0.9971, -0.469], p-value = 0.0001), and hospital LOS (beta coefficient [95%CI]: -0.68 [-0.913, -0.452], p-value = 0.0001). Conclusion: Early initiation of dexamethasone within three days of ICU admission in COVID-19 critically ill patients was associated with a mortality benefit. Additionally, it was associated with shorter MV duration, hospital, and ICU LOS.


2018 ◽  
Vol 46 (3) ◽  
pp. 1254-1262 ◽  
Author(s):  
Surat Tongyoo ◽  
Tanuwong Viarasilpa ◽  
Chairat Permpikul

Objective To compare the outcomes of patients with and without a mean serum potassium (K+) level within the recommended range (3.5–4.5 mEq/L). Methods This prospective cohort study involved patients admitted to the medical intensive care unit (ICU) of Siriraj Hospital from May 2012 to February 2013. The patients’ baseline characteristics, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, serum K+ level, and hospital outcomes were recorded. Patients with a mean K+ level of 3.5 to 4.5 mEq/L and with all individual K+ values of 3.0 to 5.0 mEq/L were allocated to the normal K+ group. The remaining patients were allocated to the abnormal K+ group. Results In total, 160 patients were included. Their mean age was 59.3±18.3 years, and their mean APACHE II score was 21.8±14.0. The normal K+ group comprised 74 (46.3%) patients. The abnormal K+ group had a significantly higher mean APACHE II score, proportion of coronary artery disease, and rate of vasopressor treatment. An abnormal serum K+ level was associated with significantly higher ICU mortality and incidence of ventricular fibrillation. Conclusion Critically ill patients with abnormal K+ levels had a higher incidence of ventricular arrhythmia and ICU mortality than patients with normal K+ levels.


Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Akshay Shah ◽  
Killian Donovan ◽  
Anna McHugh ◽  
Manish Pandey ◽  
Louise Aaron ◽  
...  

Abstract Background Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. Methods We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. Results A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49–64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. Conclusion Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies. Graphical abstract


1996 ◽  
Vol 40 (3) ◽  
pp. 691-695 ◽  
Author(s):  
A S Benko ◽  
D M Cappelletty ◽  
J A Kruse ◽  
M J Rybak

The pharmacodynamics and pharmacokinetics of ceftazidime administered by continuous infusion and intermittent bolus over a 4-day period were compared. We conducted a prospective, randomized, crossover study of 12 critically ill patients with suspected gram-negative infections. The patients were randomized to receive ceftazidime either as a 2-g intravenous (i.v.) loading dose followed by a 3-g continuous infusion (CI) over 24 h or as 2 g i.v. every 8 h (q8h), each for 2 days. After 2 days, the patients were crossed over and received the opposite regimen. Each regimen also included tobramycin (4 to 7 mg/kg of body weight, given i.v. q24h). Eighteen blood samples were drawn on study days 2 and 4 to evaluate the pharmacokinetics of ceftazidime and its pharmacodynamics against a clinical isolate of Pseudomonas aeruginosa (R288). The patient demographics (means +/- standard deviations) were as follows: age, 57 +/- 12 years; sex, nine males and three females; APACHE II score, 15 +/- 3; diagnosis, 9 of 12 patients with pneumonia. The mean pharmacokinetic parameters for ceftazidime given as an intermittent bolus (IB) (means +/- standard deviations) were as follows: maximum concentration of drug in serum, 124.4 +/- 52.6 micrograms/ml; minimum concentration in serum, 25.0 +/- 17.5 micrograms/ml; elimination constant, 0.268 +/- 0.205 h-1; half-life, 3.48 +/- 1.61 h; and volume of distribution, 18.9 +/- 9.0 liters. The steady-state ceftazidime concentration for CI was 29.7 +/- 17.4 micrograms/ml, which was not significantly different from the targeted concentrations. The range of mean steady-state ceftazidime concentrations for the 12 patients was 10.6 to 62.4 micrograms/ml. Tobramycin peak concentrations ranged between 7 and 20 micrograms/ml. As expected, the area under the curve for the 2-g q8h regimen was larger than that for CI (P = 0.003). For IB and CI, the times that the serum drug concentration was greater than the MIC were 92 and 100%, respectively, for each regimen against the P. aeruginosa clinical isolate. The 24-h bactericidal titers in serum, at which the tobramycin concentrations were < 1.0 microgram/ml in all patients, were the same for CI and IB (1:4). In the presence of tobramycin, the area under the bactericidal titer-time curve (AUBC) was significantly greater for IB than CI (P = 0.001). After tobramycin was removed from the serum, no significant difference existed between the AUBCs for CI and IB. We conclude that CI of ceftazidime utilizing one-half the IB daily dose was equivalent to the IB treatment as judged by pharmacodynamic analysis of critically ill patients with suspected gram-negative infections. No evaluation comparing the clinical efficacies of these two dosage regimens was performed.


2020 ◽  
pp. 088506662094027
Author(s):  
Jeremy Cheuk Kin Sin ◽  
Lillian King ◽  
Emma Ballard ◽  
Stacey Llewellyn ◽  
Kevin B. Laupland ◽  
...  

Purpose: Hypophosphatemia is reported in up to 5% of hospitalized patients and ranges from 20% to 80% in critically ill patients. The consequences of hypophosphatemia for critically ill patients remain controversial. We evaluated the effect of hypophosphatemia on mortality and length of stay in intensive care unit (ICU) patients. Methods: MEDLINE, EMBASE, Cochrane Library (Reviews and Trials), and PubMed were searched for articles in English. The primary outcome was mortality and secondary outcome was length of stay. The quality of evidence was graded using a modified Newcastle-Ottawa Scale. Results: Our search yielded 828 articles and ultimately included 12 studies with 7626 participants in the analysis. Hypophosphatemia was associated with increased hospital length of stay (2.19 days [95% CI, 1.74-2.64]) and ICU length of stay (2.22 days [95% CI, 1.00-3.44]) but not mortality (risk ratio: 1.13 [95% CI, 0.98-1.31]; P = .09). Conclusions: Hypophosphatemia in ICU was associated with increased hospital and ICU length of stay but not all-cause mortality. Hypophosphatemia appears to be a marker of disease severity. Limited number of available studies and varied study designs did not allow for the ascertainment of the effect of severe hypophosphatemia on patient mortality.


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