Evaluation of zinc sulfate as an adjunctive therapy in COVID-19 critically ill patients: a two center propensity-score matched study

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.

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Evaluation of Zinc Sulfate as an Adjunctive Therapy in COVID-19 Critically Ill Patients: a Two Center Propensity-score Matched Study

10.21203/rs.3.rs-572942/v1 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Al Juhani ◽

Abdulrahman I Al Shaya ◽

Abdullah Kharbosh ◽

Raed Kensara ◽

...

Keyword(s):

Propensity Score ◽

Propensity Score Matching ◽

Critically Ill ◽

Critically Ill Patients ◽

Adjunctive Therapy ◽

Zinc Sulfate ◽

Kidney Injury ◽

Icu Stay ◽

Increased Risk ◽

Beta Coefficient

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 a 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 01 March 2020 until 31-December 2020. We assessed the association of zinc use as adjunctive therapy with the in-hospital and 30-day mortality after propensity score matching. Secondary outcomes included mechanical ventilation (MV) duration, ICU length of stay (LOS), hospital LOS, and complication (s) during ICU stay. Results: A total of 266 patients were included in this study after using propensity score matching. Zinc sulfate as adjunctive therapy during ICU stay was not associated with statistically significant reduction in 30-day mortality nor in-hospital mortality compared to those who did not receive zinc (HR= 0.65 CI = 0.41,1.01; p= 0.05 and HR= 0.67 CI = 0.45,1.00; p= 0.05; respectively). Moreover, MV duration (Beta coefficient 0.10 CI = -0.19,0.39; p= 0.48), ICU LOS (Beta coefficient 0.19 CI = -0.02,0.40; p=0.08) and hospital LOS (Beta coefficient 0.15 CI = -0.02,0.32; p=0.08) were not statistically significant between the two groups. Patients who received zinc have a higher odds of acute kidney injury (AKI) during ICU stay (OR= 1.80 CI = 1.08-3.0; p= 0.02). Conclusion: Zinc sulfate as adjunctive therapy in critically ill patients with COVID-19 may have survival benefit; however, was not statistically significant. Zinc use was linked with an increased risk of AKI development during ICU stay.

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Evaluation of low-dose aspirin use among COVID-19 critically ill patients: A Multicenter Propensity Score Matched Study

10.21203/rs.3.rs-872891/v2 ◽

2021 ◽

Author(s):

Abdullah Al Harthi ◽

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

...

Keyword(s):

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Low Dose ◽

P Value ◽

Icu Stay ◽

Dose Aspirin ◽

Low Dose Aspirin ◽

Anti Inflammatory

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.

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

10.21203/rs.3.rs-828175/v2 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

Shmeylan Al Harbi ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Hazard Ratio ◽

Icu Stay ◽

Markers Of Inflammation ◽

The Impact ◽

Statin Use

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.

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

10.21203/rs.3.rs-828175/v1 ◽

2021 ◽

Author(s):

◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

Shmeylan Al Harbi ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Hazard Ratio ◽

Icu Stay ◽

Markers Of Inflammation ◽

The Impact ◽

Statin Use

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

10.21203/rs.3.rs-828175/v3 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Ghazwa B. Korayem ◽

Ali F. Altebainawi ◽

Shmeylan Al Harbi ◽

...

Keyword(s):

Cohort Study ◽

Propensity Score ◽

Hospital Mortality ◽

Statin Therapy ◽

Critically Ill ◽

Critically Ill Patients ◽

Hazard Ratio ◽

Icu Stay ◽

Markers Of Inflammation ◽

Statin Use

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.

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Serum lactate dehydrogenase level is associated with in-hospital mortality in critically Ill patients with acute kidney injury

International Urology and Nephrology ◽

10.1007/s11255-021-02792-z ◽

2021 ◽

Author(s):

Dan Zhang ◽

Lin Shi

Keyword(s):

Acute Kidney Injury ◽

Lactate Dehydrogenase ◽

Hospital Mortality ◽

Critically Ill ◽

Critically Ill Patients ◽

Kidney Injury ◽

Lactate Dehydrogenase Level ◽

Serum Lactate ◽

Serum Lactate Dehydrogenase ◽

Serum Lactate Dehydrogenase Level

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High-dose versus low-dose haemofiltration for the treatment of critically ill patients with acute kidney injury: an updated systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2016-014171 ◽

2017 ◽

Vol 7 (10) ◽

pp. e014171 ◽

Cited By ~ 7

Author(s):

Peng Li ◽

Li-ping Qu ◽

Dong Qi ◽

Bo Shen ◽

Yi-mei Wang ◽

...

Keyword(s):

Systematic Review ◽

Acute Kidney Injury ◽

Hospital Mortality ◽

Hospital Stay ◽

Critically Ill ◽

Critically Ill Patients ◽

Low Dose ◽

Meta Analysis ◽

Kidney Injury ◽

High Dose

ObjectiveThe purpose of this study was to perform a systematic review and meta-analysis to evaluate the effect of high-dose versus low-dose haemofiltration on the survival of critically ill patients with acute kidney injury (AKI). We hypothesised that high-dose treatments are not associated with a higher risk of mortality.DesignMeta-analysis.SettingRandomised controlled trials and two-arm prospective and retrospective studies were included.ParticipantsCritically ill patients with AKI.InterventionsContinuous renal replacement therapy.Primary and secondary outcome measuresPrimary outcomes: 90-day mortality, intensive care unit (ICU) mortality, hospital mortality; secondary outcomes: length of ICU and hospital stay.ResultEight studies including 2970 patients were included in the analysis. Pooled results showed no significant difference in the 90-mortality rate between patients treated with high-dose or low-dose haemofiltration (pooled OR=0.90, 95% CI 0.73 to 1.11, p=0.32). Findings were similar for ICU (pooled OR=1.12, 95% CI 0.94 to 1.34, p=0.21) and hospital mortality (pooled OR=1.03, 95% CI 0.81 to 1.30, p=0.84). Length of ICU and hospital stay were similar between high-dose and low-dose groups. Pooled results are not overly influenced by any one study, different cut-off points of prescribed dose or different cut-off points of delivered dose. Meta-regression analysis indicated that the results were not affected by the percentage of patients with sepsis or septic shock.ConclusionHigh-dose and low-dose haemofiltration produce similar outcomes with respect to mortality and length of ICU and hospital stay in critically ill patients with AKI.This study was not registered at the time the data were collected and analysed. It has since been registered on 17 February 2017 athttp://www.researchregistry.com/, registration number: reviewregistry211.

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Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia

Journal of Intensive Care Medicine ◽

10.1177/0885066616646551 ◽

2016 ◽

Vol 32 (8) ◽

pp. 487-493 ◽

Cited By ~ 16

Author(s):

Jessica L. Elefritz ◽

Karri A. Bauer ◽

Christian Jones ◽

Julie E. Mangino ◽

Kyle Porter ◽

...

Keyword(s):

Critically Ill ◽

Critically Ill Patients ◽

Clinical Cure ◽

Statistical Significance ◽

Cohort Analysis ◽

Kidney Injury ◽

Multidrug Resistant ◽

High Dose ◽

Loading Dose ◽

Gram Negative

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

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Author Correction: Ascorbic acid as an adjunctive therapy in critically ill patients with COVID-19: a propensity score matched study

Scientific Reports ◽

10.1038/s41598-021-99146-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Aljuhani ◽

Khalid Bin Saleh ◽

Hisham A. Badreldin ◽

Abdullah Al Harthi ◽

...

Keyword(s):

Ascorbic Acid ◽

Propensity Score ◽

Critically Ill ◽

Critically Ill Patients ◽

Adjunctive Therapy ◽

Matched Study

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Adjunctive Therapy with Ascorbic in Critically Ill Patients with COVID-19: A Multicenter Propensity Score Matched Study

10.21203/rs.3.rs-227158/v1 ◽

2021 ◽

Author(s):

Khalid Al Sulaiman ◽

Ohoud Al Juhani ◽

Hisham A. Badreldin ◽

Khalid Bin Salah ◽

Abdullah Al Harthi ◽

...

Keyword(s):

Ascorbic Acid ◽

Propensity Score ◽

Propensity Score Matching ◽

Critically Ill ◽

Critically Ill Patients ◽

Lower Incidence ◽

Adjunctive Therapy ◽

P Value ◽

Relative Safety ◽

Severity Scores

Abstract Background: Due to its supposed clinical efficacy, relative safety, and low cost, ascorbic acid represents an appealing option for clinicians to utilize in the context of a global health pandemic of COVID-19 patients.Objectives: The aim of this study was to evaluate the efficacy and safety of using ascorbic acid as adjunctive therapy in critically ill patients with COVID-19. Methods: This was a multi-center, non-interventional, retrospective cohort study. All critically ill adult patients admitted to ICU with a confirmed COVID-19 between March 1st to December 31st, 2020 were included in the final analysis. The study was conducted at two large governmental tertiary hospitals in Saudi Arabia. The purpose was to investigate the association between clinical outcomes with ascorbic acid use as an adjunctive therapy in COVID-19 after propensity score matching using baseline severity scores, systemic use of corticosteroids and study centers. Results: A 739 patients were included in this study; 296 patients were included after propensity score matching. There was no association between the administration of ascorbic acid and in-hospital mortality nor 30-day ICU mortality (OR (95%CI): 0.77 (0.476, 1.234), p-value=0.2738 and OR (95%CI): 0.73 (0.438 ,1.204), p-value=0.215 respectively). Using ascorbic acid was associated with lower incidence of thrombosis compared with the non-ascorbic acid group (6.1% vs. 13% respectively); OR (95%CI): 0.42 (0.184, 0.937), p-value=0.0342).Conclusion: Ascorbic acid use as an adjunctive therapy in COVID19 critically ill patients was not associated with mortality benefits; but associated with lower incidence of thrombosis. Further studies are required to confirm these findings.

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