scholarly journals Statins’ safety and impact on the clinical outcomes in COVID-19 critically ill patients: A Multicenter, Cohort Study

Author(s):  
Khalid Al Sulaiman ◽  
Ohoud Aljuhani ◽  
Ghazwa B. Korayem ◽  
Ali F. Altebainawi ◽  
Shmeylan Al Harbi ◽  
...  

Abstract Purpose The complications of Severe Corona Virus Disease 2019 (COVID-19) are attributed to the overproduction of early response proinflammatory cytokines, causing a systemic hyperinflammatory state. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic and anti-inflammatory effects, which are independent of their cholesterol-lowering activity. This study investigates the impact of statin use on the outcome of critically ill patients with COVID-19. Methods A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on statin use during ICU stay and were matched with a propensity score which was based on patient’s age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality. Other outcomes were considered secondary... Results A total of 1049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The 30-day (hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03) and in-hospital mortality (hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004) were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin have a lower risk of hospital-acquired pneumonia (OR 0.48(95% CI 0.32, 0.69), P = < 0.001), lower levels of markers of inflammation on follow up and no increased risk of liver injury. Conclusion The use of statin during ICU stay in COVID-19 critically ill patients may have a beneficial role and survival benefits with a good safety profile.

2021 ◽  
Author(s):  
◽  
Ohoud Aljuhani ◽  
Ghazwa B. Korayem ◽  
Ali F. Altebainawi ◽  
Shmeylan Al Harbi ◽  
...  

Abstract Purpose The complications of Severe Corona Virus Disease 2019 (COVID-19) are attributed to the overproduction of early response proinflammatory cytokines, causing a systemic hyperinflammatory state. Statins are potentially a potent adjuvant therapy in COVID-19 infection due to their pleiotropic and anti-inflammatory effects, which are independent of their cholesterol-lowering activity. This study investigates the impact of statin use on the outcome of critically ill patients with COVID-19. Methods A multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on statin use during ICU stay and were matched with a propensity score which was based on patient’s age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality. Other outcomes were considered secondary... Results A total of 1049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The 30-day (hazard ratio 0.75 (95% CI 0.58, 0.98), P = 0.03) and in-hospital mortality (hazard ratio 0.69 (95% CI 0.54, 0.89), P = 0.004) were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin have a lower risk of hospital-acquired pneumonia (OR 0.48(95% CI 0.32, 0.69), P = < 0.001), lower levels of markers of inflammation on follow up and no increased risk of liver injury. Conclusion The use of statin during ICU stay in COVID-19 critically ill patients may have a beneficial role and survival benefits with a good safety profile.


2021 ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Ohoud Aljuhani ◽  
Ghazwa B. Korayem ◽  
Ali F. Altebainawi ◽  
Shmeylan Al Harbi ◽  
...  

Abstract Background The cardiovascular complications of Severe Coronavirus Disease 2019 (COVID-19) may be attributed to the hyperinflammatory state leading to increased mortality in patients with COVID-19. Statins are known to have pleiotropic and anti-inflammatory effects and may influence viral transmission along with their cholesterol-lowering activity. Thus, statin therapy is potentially a potent adjuvant therapy in COVID-19 infection. This study investigated the association of statin use on the outcome of critically ill patients with COVID-19. MethodsA multicenter, retrospective cohort study of all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on statin use during ICU stay and were matched with a propensity score based on patient’s age and admission APACHE II and SOFA scores. The primary endpoint was in-hospital mortality, while 30 days Ventilator-free days (VFDs) and ICU complications were secondary endpoints. ResultsA total of 1049 patients were eligible; 502 patients were included after propensity score matching (1:1 ratio). The 30-day (hazard ratio 0.75 (95% CI 0.58, 0.98), P=0.03) and in-hospital mortality (hazard ratio 0.69 (95% CI 0.54, 0.89), P=0.004) were significantly lower in patients who received statin therapy on multivariable cox proportional hazards regression analysis. Moreover, patients who received statin had a lower risk of hospital-acquired pneumonia (OR 0.48(95% CI 0.32, 0.69), P=<0.001), lower levels of markers of inflammation on follow up and no increased risk of liver injury. ConclusionThe use of statin during ICU stay in COVID-19 critically ill patients may have a beneficial role and survival benefits with a good safety profile.


Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Ohoud Aljuhani ◽  
Abdulrahman I. Al Shaya ◽  
Abdullah Kharbosh ◽  
Raed Kensara ◽  
...  

Abstract Background Zinc is a trace element that plays a role in stimulating innate and acquired immunity. The role of zinc in critically ill patients with COVID-19 remains unclear. This study aims to evaluate the efficacy and safety of zinc sulfate as adjunctive therapy in critically ill patients with COVID-19. Methods Patients aged ≥ 18 years with COVID-19 who were admitted to the intensive care unit (ICU) in two tertiary hospitals in Saudi Arabia were retrospectively assessed for zinc use from March 1, 2020 until March 31, 2021. After propensity score matching (1:1 ratio) based on the selected criteria, we assessed the association of zinc used as adjunctive therapy with the 30-day mortality. Secondary outcomes included the in-hospital mortality, ventilator free days, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. Results A total of 164 patients were included, 82 patients received zinc. Patients who received zinc sulfate as adjunctive therapy have a lower 30-day mortality (HR 0.52, CI 0.29, 0.92; p = 0.03). On the other hand, the in-hospital mortality was not statistically significant between the two groups (HR 0.64, CI 0.37–1.10; p = 0.11). Zinc sulfate use was associated with a lower odds of acute kidney injury development during ICU stay (OR 0.46 CI 0.19–1.06; p = 0.07); however, it did not reach statistical significance. Conclusion The use of zinc sulfate as an additional treatment in critically ill COVID-19 patients may improve survival. Furthermore, zinc supplementation may have a protective effect on the kidneys.


2021 ◽  
Author(s):  
Abdullah Al Harthi ◽  
Khalid Al Sulaiman ◽  
Ohoud Aljuhani ◽  
Ghazwa B. Korayem ◽  
Ali F. Altebainawi ◽  
...  

Abstract BackgroundMultiple medications with anti-inflammatory effects have been used to manage the hyper-inflammatory response associated with COVID-19. Aspirin is used widely as a cardioprotective agent due to its antiplatelet and anti-inflammatory properties. Its role in hospitalized COVID-19 patients has been assessed and evaluated in the literature. However, no data regards its role in COVID-19 critically ill patients. Therefore, this study aims to evaluate the use of low-dose aspirin (81-100 mg) and its impact on outcomes in COVID-19 critically ill patients. MethodThis is a multicenter, retrospective cohort study for all adult critically ill patients with confirmed COVID-19 admitted to Intensive Care Units (ICUs) between March 1, 2020, and March 31, 2021. Eligible patients were classified into two groups based on aspirin use during ICU stay. The primary outcome is the in-hospital mortality; other outcomes were considered secondary. Propensity score-matched used based on patient’s age, SOFA score, MV status within 24 hours of ICU admission, prone position status, ischemic heart disease (IHD), and stroke as co-existing illness. We considered a P value of < 0.05 statistically significant.ResultsA total of 1033 patients were eligible; 352 patients were included after propensity score matching (1:1 ratio). The in-hospital mortality (HR (95%CI): 0.73 (0.56, 0.97), p-value=0.03) were lower in patients who received aspirin during hospital stay. On the other hand, patients who received aspirin have a higher risk of major bleeding compared to the control group (OR (95%CI): 2.92 (0.91, 9.36), p-value=0.07); but was not statistically significant.ConclusionAspirin use in COVID-19 critically ill patients may have a mortality benefit; nevertheless, it may be linked with an increased risk of significant bleeding. The benefit-risk evaluation for aspirin usage during an ICU stay should be tailored to each patient.


2022 ◽  
Vol 8 ◽  
Author(s):  
Boshen Yang ◽  
Sixuan Xu ◽  
Di Wang ◽  
Yu Chen ◽  
Zhenfa Zhou ◽  
...  

Background: Hypertension is a rather common comorbidity among critically ill patients and hospital mortality might be higher among critically ill patients with hypertension (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg). This study aimed to explore the association between ACEI/ARB medication during ICU stay and all-cause in-hospital mortality in these patients.Methods: A retrospective cohort study was conducted based on data from Medical Information Mart for Intensive Care IV (MIMIC-IV) database, which consisted of more than 40,000 patients in ICU between 2008 and 2019 at Beth Israel Deaconess Medical Center. Adults diagnosed with hypertension on admission and those had high blood pressure (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg) during ICU stay were included. The primary outcome was all-cause in-hospital mortality. Patients were divided into ACEI/ARB treated and non-treated group during ICU stay. Propensity score matching (PSM) was used to adjust potential confounders. Nine machine learning models were developed and validated based on 37 clinical and laboratory features of all patients. The model with the best performance was selected based on area under the receiver operating characteristic curve (AUC) followed by 5-fold cross-validation. After hyperparameter optimization using Grid and random hyperparameter search, a final LightGBM model was developed, and Shapley Additive exPlanations (SHAP) values were calculated to evaluate feature importance of each feature. The features closely associated with hospital mortality were presented as significant features.Results: A total of 15,352 patients were enrolled in this study, among whom 5,193 (33.8%) patients were treated with ACEI/ARB. A significantly lower all-cause in-hospital mortality was observed among patients treated with ACEI/ARB (3.9 vs. 12.7%) as well as a lower 28-day mortality (3.6 vs. 12.2%). The outcome remained consistent after propensity score matching. Among nine machine learning models, the LightGBM model had the highest AUC = 0.9935. The SHAP plot was employed to make the model interpretable based on LightGBM model after hyperparameter optimization, showing that ACEI/ARB use was among the top five significant features, which were associated with hospital mortality.Conclusions: The use of ACEI/ARB in critically ill patients with hypertension during ICU stay is related to lower all-cause in-hospital mortality, which was independently associated with increased survival in a large and heterogeneous cohort of critically ill hypertensive patients with or without kidney dysfunction.


2020 ◽  
Author(s):  
Zehao Wu ◽  
Huili Li ◽  
Kaihua Liao ◽  
Yun Wang

Abstract BackgroundDelirium is a common complication in ICU patients, and it can significantly increase the length of hospital stay and cost. Dexamethasone is widely used in various inflammatory diseases and is a glucocorticoid commonly used in critically ill patients. There are no studies on the effect of dexamethasone on the development of delirium in critically ill patients, therefore, this study aimed to confirm the effect of dexamethasone use and the dose on the incidence of delirium and patient prognosis in critically ill patients through a large cohort study.MethodsA retrospective cohort study was conducted using data extracted from the MIMIC III database, and the primary outcome was the development of delirium, using multivariate logistic regression analysis to reveal the relationship between dexamethasone and delirium. Secondary endpoints were in-hospital mortality, total length of stay and length of ICU stay, and the relationship between dexamethasone and prognosis was assessed with Cox proportional hazards models. The Lowess smoothing technique was used to investigate the dose correlation between dexamethasone and outcomes, subgroup analysis was used to account for heterogeneity, and different correction models and propensity matching analysis were used to eliminate potential confounders.ResultsFinally, 38,509 patients were included, and 2,204 (5.7%) used dexamethasone. A significantly higher incidence of delirium (5.0% vs. 3.4%, P < 0.001), increased in-hospital mortality (15.0% vs. 11.3%, P < 0.001), and longer length of stay and ICU stay were observed in patients taking dexamethasone compared with those not taking dexamethasone. Multivariate logistic and Cox regression analyses confirmed that dexamethasone was significantly associated with delirium (adjusted OR = 1.45, 95% CI = 1.08-1.95, P = 0.014) and in-hospital mortality (adjusted HR = 1.19, 95% CI = 1.02-1.40, P = 0.032). The risk of delirium and in-hospital death was lower with dexamethasone less than 10 mg, and subjects with 10-14 mg had the shortest length of hospital stay.ConclusionsThis study demonstrated that the use of dexamethasone in critically ill patients exacerbated the occurrence of delirium, while increasing the risk of in-hospital death and length of stay, and the use of low-dose dexamethasone had a lower risk of delirium and death, which appeared to be safer.


Antibiotics ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 557
Author(s):  
Matthias Gijsen ◽  
Erwin Dreesen ◽  
Ruth Van Daele ◽  
Pieter Annaert ◽  
Yves Debaveye ◽  
...  

The impact of ceftriaxone pharmacokinetic alterations on protein binding and PK/PD target attainment still remains unclear. We evaluated pharmacokinetic/pharmacodynamic (PK/PD) target attainment of unbound ceftriaxone in critically ill patients with severe community-acquired pneumonia (CAP). Besides, we evaluated the accuracy of predicted vs. measured unbound ceftriaxone concentrations, and its impact on PK/PD target attainment. A prospective observational cohort study was carried out in adult patients admitted to the intensive care unit with severe CAP. Ceftriaxone 2 g q24h intermittent infusion was administered to all patients. Successful PK/PD target attainment was defined as unbound trough concentrations above 1 or 4 mg/L throughout the whole dosing interval. Acceptable overall PK/PD target attainment was defined as successful target attainment in ≥90% of all dosing intervals. Measured unbound ceftriaxone concentrations (CEFu) were compared to unbound concentrations predicted from various protein binding models. Thirty-one patients were included. The 1 mg/L and 4 mg/L targets were reached in 26/32 (81%) and 15/32 (47%) trough samples, respectively. Increased renal function was associated with the failure to attain both PK/PD targets. Unbound ceftriaxone concentrations predicted by the protein binding model developed in the present study showed acceptable bias and precision and had no major impact on PK/PD target attainment. We showed suboptimal (i.e., <90%) unbound ceftriaxone PK/PD target attainment when using a standard 2 g q24h dosing regimen in critically ill patients with severe CAP. Renal function was the major driver for the failure to attain the predefined targets, in accordance with results found in general and septic ICU patients. Interestingly, CEFu was reliably predicted from CEFt without major impact on clinical decisions regarding PK/PD target attainment. This suggests that, when carefully selecting a protein binding model, CEFu does not need to be measured. As a result, the turn-around time and cost for ceftriaxone quantification can be substantially reduced.


2021 ◽  
Author(s):  
Khalid Al Sulaiman ◽  
Abdulrahman Alshaya ◽  
Amjad Alsaeed ◽  
Nadiyah Alshehri ◽  
Ramesh Vishwakarma ◽  
...  

Abstract BackgroundVancomycin is a commonly used antibiotic in critically ill patients for various indications. Critical illness imposes pharmacokinetic-pharmacodynamics challenges which makes optimizing vancomycin in this population cumbersome. Data are scarce on the clinical impact of time to therapeutic trough levels of vancomycin in critically ill patients. Objective (s)The aim of this study to evaluate the timing to achieve therapeutic trough level vancomycin on 30-day mortality in critically ill patients.SettingAdult critically ill patients admitted to intensive care units (ICUs) between January 1st, 2017 and December 31st, 2018 at a tertiary teaching hospital.MethodA retrospective cohort study for all adult critically ill patients aged 18 years or older with confirmed gram-positive infection and received vancomycin. We compared early (<48 hours) versus late (≥ 48 hours) attainment of vancomycin therapeutic trough levels. Main outcomesPrimary outcome was the 30-day mortality in critically ill patients. Secondary outcomes were development of resistant organisms, eradicating microorganisms within 4-5 days of vancomycin initiation, vancomycin-induced acute kidney injury (AKI), and ICU LOS. ResultsTwo hundred and nine patients were included. No significant differences between comparative groups in baseline characteristics. Achieving therapeutic levels were associated with better survival at 30 days (OR: 0.48; 95% CI [0.26-0.87]; p<0.01). Additionally, patients who achieved therapeutic levels of vancomycin early were less likely to develop resistant organisms (OR=0.08; 95% CI [0.01-0.59]; p=0.01). Acute kidney injury (AKI) and ICU length of stay (LOS) were not significant between the two groups.ConclusionEarly attainment of vancomycin therapeutic levels was associated with possible survival benefit.


2021 ◽  
Vol 8 ◽  
Author(s):  
Shao-shuo Yu ◽  
Jian Jin ◽  
Ren-qi Yao ◽  
Bo-li Wang ◽  
Lun-yang Hu ◽  
...  

Background: A large number of studies have been conducted to determine whether there is an association between preadmission statin use and improvement in outcomes following critical illness, but the conclusions are quite inconsistent. Therefore, this meta-analysis aims to include the present relevant PSM researches to examine the association of preadmission use of statins with the mortality of critically ill patients.Methods: The PubMed, Web of Science, Embase electronic databases, and printed resources were searched for English articles published before March 6, 2020 on the association between preadmission statin use and mortality in critically ill patients. The included articles were analyzed in RevMan 5.3. The Newcastle-Ottawa Scale (NOS) was used to conduct quality evaluation, and random/fixed effects modeling was used to calculate the pooled ORs and 95% CIs. We also conducted subgroup analysis by outcome indicators (30-, 90-day, hospital mortality).Results: All six PSM observational studies were assessed as having a low risk of bias according to the NOS. For primary outcome—overall mortality, the pooled OR (preadmission statins use vs. no use) across the six included studies was 0.86 (95% CI, 0.76–0.97; P = 0.02). For secondary outcome—use of mechanical ventilation, the pooled OR was 0.94 (95% CI, 0.91–0.97; P = 0.0005). The corresponding pooled ORs were 0.67 (95% CI, 0.43–1.05; P = 0.08), 0.91 (95% CI, 0.83–1.01; P = 0.07), and 0.86 (95% CI, 0.83–0.89; P &lt; 0.00001) for 30-, 90-day, and hospital mortality, respectively.Conclusions: Preadmission statin use is associated with beneficial outcomes in critical ill patients, indicating a lower short-term mortality, less use of mechanical ventilation, and an improvement in hospital survival. Further high-quality original studies or more scientific methods are needed to draw a definitive conclusion.


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