Clonidine safety and effectiveness in the management of suspected paroxysmal sympathetic hyperactivity post-traumatic brain injury: A retrospective cohort study.

INTRODUCTION: Traumatic brain injury (TBI) is a leading cause of mortality and morbidity worldwide. In addition, TBI may cause paroxysmal sympathetic hyperactivity (PSH), which is associated with poor clinical outcomes. This study aimed to evaluate the safety and effectiveness of clonidine in patients with TBI and suspected PSH. METHODS: A retrospective cohort study for critically ill patients with TBI with suspected PSH admitted to intensive care units (ICUs) from 1 May 2016 to 31 January 2020 at a tertiary academic medical center. Eligible patients were categorized based on clonidine use during their ICU stay (Clonidine group vs. Control group). The primary outcome was the improvement in functional outcomes during ICU stay, defined by a delta Glasgow Coma Score (GCS). Secondary outcomes included ICU and hospital length of stay, heart rate variation, and 90-day mortality. RESULTS: A total of 2915 patients were screened, of which 169 were included. Based on multiple regression analysis, patients who received clonidine showed better improvement in functional outcomes by a higher mean delta GCS than patients who did not (Beta Coeff. 0.41; CI: 0.07 - 0.74; P = 0.02). In addition, the patient's GCS upon ICU discharge and IV opioids requirement on day three were higher in the clonidine group than control (beta coefficient (95% CI): 0.18 (0.03, 0.32); p = 0.02 and beta coefficient (95% CI): 1.38 (0.24, 2.52); p = 0.02, respectively). No statistical differences were observed in any of the other secondary outcomes after adjusting for confounders. CONCLUSION: This study found that patients who received clonidine had better functional outcomes during their ICU stay, as shown by their delta GCS than those who did not. Other outcomes were similar between the groups. More data are needed to explore the role of clonidine in patients with TBI with suspected PSH.

Practical Guide for Anticoagulant and Antiplatelet Reversal in Clinical Practice.

In recent years, anticoagulant and antiplatelet use have increased over the past years for the prevention and treatment of several cardiovascular conditions. Due to the rising use of antithrombotic medications and the complexity of specific clinical cases requiring such therapies, bleeding remains the primary concern among patients using antithrombotics. Direct oral anticoagulants (DOACs) include rivaroxaban, apixaban, edoxaban, and betrixaban. Direct thrombin inhibitors (DTIs) include argatroban, bivalirudin, and dabigatran. DOACs are associated with lower rates of fatal, life-threatening, and significant bleeding risks compared to those of warfarin. The immediate reversal of these agents can be indicated in an emergency setting. Antithrombotic reversal recommendations are still in development. Vitamin K and prothrombin complex concentrate (PCCs) can be used for warfarin reversal. Andexanet alfa and idarucizumab are specific reversal agents for DOACs and DTIs, respectively. Protamine sulfate is the solely approved reversal agent for unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). However, there are no specific reversal agents for antiplatelets. This article aims to provide a practical guide for clinicians regarding the reversal of anticoagulants and antiplatelets in clinical practice based on the most recent studies.

Therapeutic Plasma Exchange and Supratherapeutic Levels of Unfractionated Heparin in the Management of Critically Ill Patient with Myasthenia Gravis: A Case Report.

BACKGROUND Therapeutic plasma exchange (TPE) is an extracorporeal method of filtration indicated in several conditions, including myasthenia gravis (MG). The removal and replacement of plasma through TPE affect the level of coagulation factors, suggesting alterations in homeostasis. TPE also has the potential to remove medications from the plasma. Insufficient data are available that evaluate the effect of TPE on certain medications, such as unfractionated heparin (UFH). CASE REPORT We report a case of a 78-year-old woman with MG. She underwent a thymectomy complicated by phrenic nerve injury and respiratory failure, requiring admission to the Intensive Care Unit (ICU) and mechanical ventilation. She developed a provoked left upper extremity deep venous thrombosis and started on therapeutic UFH with a target activated partial thromboplastin time (aPTT) of 50 to 80 seconds. Despite being on immunosuppressants, additional therapy with TPE was deemed necessary for her MG exacerbation. Therefore, she received 5 sessions of TPE, given every other day. Interestingly, while on TPE therapy, the aPTT increased significantly after each administration, with TPE reaching >170 seconds in some instances. As a precautionary measure, heparin infusion was held for 1 day based on the institutional heparin protocol and the physician's decision. Fortunately, the patient did not develop any bleeding complications. CONCLUSIONS TPE treatment may temporarily deplete the coagulation factors, leading to supratherapeutic aPTT levels. UFH dose adjustment and frequent assessment of aPTT levels are essential during TPE treatment to minimize serious bleeding complications. Future studies with a larger sample size are required to focus on understanding the effect of TPE on medications.

Colistin Loading Dose in Septic Patients with Gram Negative Infections.

Purpose: Intravenous (IV) colistin is commonly used to treat multidrug-resistant gram-negative infections. It is primarily eliminated renally and may induce acute kidney injury (AKI) at a rate of up to 53%. Consequently, septic patients who require colistin administration have an additional risk of developing AKI. The aim of this study is to investigate clinical failure and AKI predictors for septic patients treated with IV colistin. Methods: This retrospective cohort study was conducted at a tertiary teaching hospital in Saudi Arabia. Adult septic patients with suspected or confirmed gram-negative infections who received colistin admitted to the hospital between May 2016 and December 2020 were screened after obtaining IRB approval. AKI was defined based on the AKI Network criteria. We investigated the incidence of clinical failure based on colistin dosing and AKI risk factors, such as the development of septic shock, severity of illness, and medication co-administration using a multiple logistic regression model. Results: After screening 163 patients, 103 patients were included in the analysis. No difference was observed between the colistin dosing strategies for clinical failure. Of the included predictors, development of septic shock (OR: 3.75; 95% CI 1.18-13.15), carbapenem co-administration (OR, 3.96; 95% CI, 1.134-15.57) were associated with an increased risk of AKI. The other factors were not significant predictors. Conclusion: Clinical failure was not affected by colistin dosing strategies in our cohort of patients with sepsis. Moreover, the co-administration of carbapenems and the development of septic shock may increase the risk of inducing AKI in adult septic patients treated with IV colistin. Further studies are required to confirm these findings.

Association between phosphate disturbances and mortality among critically ill patients with sepsis or septic shock.

OBJECTIVE: The aim of this study is to examine the association of hypophosphatemia and hyperphosphatemia on the first day of ICU admission with mortality in septic critically ill patients. METHODS: In this retrospective cohort study, all adult patients who were admitted to the medical-surgical ICUs between 2014 and 2017 with sepsis or septic shock were categorized as having hypophosphatemia, normophosphatemia and hyperphosphatemia based on day 1 serum phosphate values. We compared the clinical characteristics and outcomes between the three groups. We used multivariate analysis to examine the association of hypophosphatemia and hyperphosphatemia with these outcomes. RESULTS: Of the 1422 patients enrolled in the study, 188 (13%) had hypophosphatemia, 865 (61%) normophosphatemia and 369 (26%) had hyperphosphatemia. The patients in the hyperphosphatemia group had significantly lower GCS, higher APACHE II scores, higher serum creatinine, increased use of vasopressors, and required more mechanical ventilation with lower PaO2/FiO2 ratio compared with the other two groups. In addition, the hyperphosphatemia group showed significantly higher ICU and hospital mortality in comparison with the other two groups. CONCLUSION: Hyperphosphatemia and not hypophosphatemia on the first ICU admission day was associated with an increase in the ICU and hospital mortality in septic critically ill patients.

Clinical features and outcomes of critically ill patients with coronavirus disease 2019 (COVID-19): A multicenter cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) manifested by a broad spectrum of symptoms, ranging from asymptomatic manifestations to severe illness and death. The purpose of the study was to extensively describe the clinical features and outcomes in critically ill patients with COVID-19 in Saudi Arabia. METHOD: This was a multicenter, non-interventional cohort study for all critically ill patients aged 18 years or older, admitted to intensive care units (ICUs) between March 1 to August 31, 2020, with an objectively confirmed diagnosis of COVID-19. The diagnosis of COVID-19 was confirmed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) on nasopharyngeal and/or throat swabs. Multivariate logistic regression and generalized linear regression were used. We considered a P value of <0.05 statistically significant. RESULTS: A total of 560 patients met the inclusion criteria. An extensive list of clinical features was associated with higher 30-day ICU mortality rates, such as requiring mechanical ventilation (MV) or developing acute kidney injury within 24 hours of ICU admission, higher body temperature, white blood cells, blood glucose level, serum creatinine, fibrinogen, procalcitonin, creatine phosphokinase, aspartate aminotransferase, and total iron-binding capacity. During ICU stay, the most common complication was respiratory failure that required MV (71.4%), followed by acute kidney injury (AKI) and thrombosis with a proportion of 46.8% and 11.4%, respectively. CONCLUSION: Among patients with COVID-19 who were admitted to the ICU, several variables were associated with an increased risk of ICU mortality at 30 days. Respiratory failure that required MV, AKI, and thrombosis were the most common complications during ICU stay.

Association between ß-blocker use and mortality in critically ill patients: a nested cohort study.

BACKGROUND: ß-blockers have several indications in critically ill patients and are commonly used. The aim of this study is to examine the relationship between the use of ß-blockers in critically ill patients and mortality. METHODS: This was a nested cohort study in which all medical-surgical ICU patients (N = 523) enrolled in a randomized clinical trial of intensive insulin therapy (ISRCTN07413772) were grouped according to ß-blocker use during ICU stay. To account for the indication of ß-blockers, we constructed a propensity score using selected clinically-relevant and statistically-significant variables related to ß-blocker exposure and outcome. The primary endpoints were all-cause ICU and hospital mortality. Secondary endpoints were the development of severe sepsis during ICU stay, ICU and hospital length of stay, and mechanical ventilation duration. Using multivariable models, we adjusted the associations of ß-blockers and these outcomes to the propensity score. RESULTS: Of the 523 patients enrolled in the study, 89 (17.0%) received ß-blockers during their ICU stay. There were no significant associations between ß-blocker therapy and ICU mortality (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 0.83-2.9, P = 0.16), hospital mortality (aOR 1.09, 95% CI 0.99-1.20, P = 0.73), the risk of ICU-acquired severe sepsis (aOR 1.67, 95% CI 0.95-2.97, P = 0.08), mechanical ventilation duration (P = 0.17), or ICU length of stay (P = 0.22). However, ß-blocker use was associated with increased ICU and hospital mortality among nondiabetic patients (aOR 2.93, 95% CI 1.19-7.23, and 2.43, 95% CI 1.05-5.64, respectively). CONCLUSIONS: Our study showed that ß-blockers during the ICU stay had no significant association with mortality or morbidity. However, ß-blocker therapy was associated with increased mortality in non-diabetic patients. TRIAL REGISTRATION: ISRCTN07413772 ; (dated 13.07.2005).

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.

OBJECTIVE: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. STUDY SELECTION: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. DATA SOURCES: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. DATA EXTRACTION: Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. DATA SYNTHESIS: Use of aspirin was associated with a 7% (95% CI, 2-12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I = 61.6%). CONCLUSIONS: These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients.

BACKGROUND: Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery. METHODS: Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2-0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT). RESULTS: Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding. CONCLUSIONS: Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2-0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.

Assessment and comparison of CHADS2, CHA2DS2-VASc, and HAS-BLED scores in patients with atrial fibrillation in Saudi Arabia.

AIMS: No previous reports on the utilization of CHADS2, CHA2DS2-VASc, and HAS-BLED scores in atrial fibrillation (AF) patients in Saudi Arabia have been identified in the literature. The main objectives of this study were to assess and compare the distribution of CHADS2, CHA2DS2-VASc, and HAS-BLED scores and to identify the most common risk factors for stroke and bleeding among AF patients attending clinical pharmacists managed anticoagulation clinic. SETTINGS AND DESIGN: This cross-sectional study was conducted over 2 months period at clinical pharmacists managed anticoagulation clinic. METHODS: CHADS2, CHA2DS2-VASc, and HAS-BLED scores were calculated and compared for all eligible patients. RESULTS: Two hundred and sixty-four patients with AF were included in the analysis. The number of patients at low risk for stroke was found to be 14 (5.3%) using CHADS2 and only 4 (1.5%) using CHA2DS2-VASc. On the other hand, 64 patients (24.2%) were found at moderate risk for stroke using CHADS2 compared with 17 patients (6.4%) using CHA2DS2-VASc. Most of the patients were found to be at high risk for stroke using either the CHADS2 (70.5%) and CHA2DS2-VASc (92%). The study also revealed that most of the patients were at moderate (63.3%) to high (27.7%) risk of bleeding. CONCLUSIONS: The results of this study show that the percentage of patients at high risk for stroke and bleeding is very high. The study revealed that this could be attributed to the high prevalence of modifiable risk factors for stroke and for bleeding in Saudi patients with AF.

Association between aspirin therapy and the outcome in critically ill patients: a nested cohort study.

BACKGROUND: Antiplatelet therapy may attenuate the undesirable effects of platelets on the inflammatory cascades in critical illness. The objective of this study was to evaluate the association between aspirin therapy during intensive care unit (ICU) stay and all-cause mortality. METHODS: This was a nested cohort study within two randomized controlled trials in which all enrolled patients (N = 763) were grouped according to aspirin intake during ICU stay. The primary endpoints were all-cause ICU mortality and hospital mortality. Secondary endpoints included the development of severe sepsis during the ICU stay, ICU and hospital length of stay and the duration of mechanical ventilation. Propensity score was used to adjust for clinically and statistically relevant variables. RESULTS: Of the 763 patients, 154 patients (20 %) received aspirin. Aspirin therapy was not associated with a reduction in ICU mortality (adjusted OR 1.18, 95 % CI 0.69-2.02, P = 0.55) nor with hospital mortality (adjusted OR 0.95, 95 % CI 0.61-1.50, P = 0.82). Aspirin use had no preferential association with mortality among any of the study subgroups. Additionally, aspirin therapy was associated with higher risk of ICU-acquired severe sepsis, and increased mechanical ventilation duration and ICU length of stay. CONCLUSION: Our study showed that the use of aspirin in critically ill patients was not associated with lower mortality, but rather with an increased morbidity. TRIAL REGISTRATION NUMBER: ISRCTN07413772 and ISRCTN96294863 .

The association between statin therapy during intensive care unit stay and the incidence of venous thromboembolism: a propensity score-adjusted analysis.

BACKGROUND: Studies have shown that statins have pleiotropic effects on inflammation and coagulation; which may affect the risk of developing venous thromboembolism (VTE). The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) stay and the incidence of VTE in critically ill patients. METHODS: This was a post-hoc analysis of a prospective observational cohort study of patients admitted to the intensive care unit between July 2006 and January 2008 at a tertiary care medical center. The primary endpoint was the incidence of VTE during ICU stay up to 30 days. Secondary endpoint was overall 30-day hospital mortality. Propensity score was used to adjust for clinically and statistically relevant variables. RESULTS: Of the 798 patients included in the original study, 123 patients (15.4%) received statins during their ICU stay. Survival analysis for VTE risk showed that statin therapy was not associated with a reduction of VTE incidence (crude hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.28-1.54, P=0.33 and adjusted HR 0.63, 95% CI 0.25-1.57, P=0.33). Furthermore, survival analysis for hospital mortality showed that statin therapy was not associated with a reduction in hospital mortality (crude HR 1.26, 95% CI 0.95-1.68, P=0.10 and adjusted HR 0.98, 95% CI 0.72-1.36, P=0.94). CONCLUSION: Our study showed no statistically significant association between statin therapy and VTE risk in critically ill patients. This question needs to be further studied in randomized control trials.

Association between statin therapy and outcomes in critically ill patients: a nested cohort study.

BACKGROUND: The effect of statin therapy on mortality in critically ill patients is controversial, with some studies suggesting a benefit and others suggesting no benefit or even potential harm. The objective of this study was to evaluate the association between statin therapy during intensive care unit (ICU) admission and all-cause mortality in critically ill patients. METHODS: This was a nested cohort study within two randomised controlled trials conducted in a tertiary care ICU. All 763 patients who participated in the two trials were included in this study. Of these, 107 patients (14%) received statins during their ICU stay. The primary endpoint was all-cause ICU and hospital mortality. Secondary endpoints included the development of sepsis and severe sepsis during the ICU stay, the ICU length of stay, the hospital length of stay, and the duration of mechanical ventilation. Multivariate logistic regression was used to adjust for clinically and statistically relevant variables. RESULTS: Statin therapy was associated with a reduction in hospital mortality (adjusted odds ratio [aOR] = 0.60, 95% confidence interval [CI] 0.36-0.99). Statin therapy was associated with lower hospital mortality in the following groups: patients >58 years of age (aOR = 0.58, 95% CI 0.35-0.97), those with an acute physiology and chronic health evaluation (APACHE II) score >22 (aOR = 0.54, 95% CI 0.31-0.96), diabetic patients (aOR = 0.52, 95% CI 0.30-0.90), patients on vasopressor therapy (aOR = 0.53, 95% CI 0.29-0.97), those admitted with severe sepsis (aOR = 0.22, 95% CI 0.07-0.66), patients with creatinine ≤ 100 µmol/L (aOR = 0.14, 95% CI 0.04-0.51), and patients with GCS ≤ 9 (aOR = 0.34, 95% CI 0.17-0.71). When stratified by statin dose, the mortality reduction was mainly observed with statin equipotent doses ≥ 40 mg of simvastatin (aOR = 0.53, 95% CI 0.28-1.00). Mortality reduction was observed with simvastatin (aOR = 0.37, 95% CI 0.17-0.81) but not with atorvastatin (aOR = 0.80, 95% CI 0.84-1.46). Statin therapy was not associated with a difference in any of the secondary outcomes. CONCLUSION: Statin therapy during ICU stay was associated with a reduction in all-cause hospital mortality. This association was especially noted in high-risk subgroups. This potential benefit needs to be validated in a randomised, controlled trial.