Dexmedetomidine for Reducing Mortality in Patients with Septic Shock: A Randomized Controlled Trial (DecatSepsis).

BACKGROUND: Sepsis, especially septic shock, and its complications have been linked to the hyperadrenergic stress response. RESEARCH QUESTION: Does decatecholaminization with dexmedetomidine (DEX) lower the in-hospital mortality in septic shock patients? STUDY DESIGN AND METHODS: This open-label randomized controlled trial assessed the effects of a heart rate (HR)-calibrated DEX infusion on in-hospital mortality in patients with septic shock and HR >90 beats per minute (bpm), whether they are mechanically ventilated or not. DEX was infused for 48 hours to maintain the HR at 60-90 bpm. Mechanically ventilated patients received conventional sedation in both groups. Other outcomes were the norepinephrine (NE) equivalent dose, the need for additional vasopressor, APACHE-II score, persistent atrial fibrillation (AF), and C-reactive protein (CRP). RESULTS: In 90 patients of either sex, DEX reduced the mean HR over the first three days in the ICU by 11.2 bpm (95% CI -17 to -5) (P < 0.001). The in-hospital mortality risk ratio (RR) was 0.68, 95% CI 0.43 to 1.07, P = 0.091. The DEX group received an NE equivalent dose of 0.55 (0.37-0.82) mcg/kg/min vs. 0.61 (0.47-0.89) (P = 0.121). DEX reduced the epinephrine infusion rescue: relative risk reduction = 0.6 (95% CI 0.06 to 0.93), P = 0.025. The RR of persistent AF was 0.47; 95% CI 0.21 to 0.99; P = 0.05. DEX reduced the median APACHE-II score on the third day by -6; 95% CI -10 to -2; P =0.003; and the mean CRP concentration by -40 mg/dl (95% CI of -78 to -3.4, P = 0.033). INTERPRETATION: The study was underpowered to detect a reduction in in-hospital mortality or NE equivalent dose in septic shock patients with DEX. However, DEX might reduce epinephrine infusion rescue, persistent AF, the APACHE-II score, and CRP.

Atorvastatin for reduction of 28-day mortality in severe and critical COVID-19 patients: a randomized controlled trial.

BACKGROUND: COVID-19 is an abnormal host response to the SARS-CoV-2 infection, which is associated with endothelial dysfunction and multi-organ failure. Atorvastatin has been proposed to reduce COVID-19 severity and mortality in chronic and de-novo users. METHODS: This randomized double-blind trial included 220 COVID-19 patients admitted to Mansoura University's isolation hospital in Egypt. One hundred and ten cases were given 40 mg of atorvastatin once daily for 28 days (group A), while 110 received a placebo (group B). All patients received treatment as per hospital protocol. The primary outcome is all-cause mortality at 28 days. We also tracked 6-month mortality, time to clinical improvement, the risk of invasive mechanical ventilation, acute kidney injury, potential adverse events, and hospital and intensive care length of stay. RESULTS: The 28-day all-cause mortality was 52/104 (50%) in group A vs. 54/103 (52.4%) in group B, odds ratio (OR) = 0.907 (0.526, 1.565), P = 0.727; adjusted OR = 0.773 (0.407, 1.47), P = 0.433. Six-month mortality occurred in 53/102 (52%) and 59/79 (60.8%) in group A vs. B, respectively, P = 0.208. Among hospital survivors in group A vs. group B, the median time to clinical improvement was 10 days (7-14) vs. 10 (7-15), P = 0.715; the duration of hospital stay was 10 days (7-14) vs. 10 (8-17), P = 0.378. Discontinuation was higher in group B (four vs. one), but statistically insignificant, P = 0.369. CONCLUSIONS: In adults with severe or critical COVID-19, atorvastatin did not reduce the risk of 28-day or 6-month mortality and did not shorten the length of hospital stay or time to clinical improvement. Trial registration Clinical Trial Registry (NCT04952350) on July 1st, 2021. https://clinicaltrials.gov/ct2/show/NCT04952350.

Intraoperative Optic Nerve Sheath Diameter as a Predictor of Early Tacrolimus Neurotoxicity after Living Donor Liver Transplantation.

BACKGROUND: During liver transplantation, graft reperfusion triggers cerebral hyperemia, increases intracranial pressure, and disrupts the blood-brain barrier, thereby increasing the risk for immunosuppression neurotoxicity. Therefore, we tested the intraoperative optic nerve sheath diameter (ONSD) for predicting tacrolimus neurotoxicity after liver transplantation. BASIC PROCEDURES: We prospectively included 100 adult patients who underwent living donor liver transplantation. The ultrasonographic ONSD 5 min after reperfusion was used as the index test, whereas the occurrence of early tacrolimus neurotoxicity was used as the reference. The area under the receiver operating characteristic curve (AUROC) was used to estimate the ONSD prediction accuracy. We reported the specificity and sensitivity of ONSD 5 and 30 min after reperfusion. Cutoffs were derived from the ROC curves. In addition, we used regression to control for confounders while testing the association between the ONSD and tacrolimus neurotoxicity. MAIN FINDINGS: The AUROC at T3 was 0.74 (95% confidence interval (CI), 0.63-0.85, P < 0.001). An ONSD of ≥6.4 mm at T3 had an 86% sensitivity (95% CI, 68%-96%) and 53% specificity (95% CI, 41%-65%). An ONSD of ≥6.4 mm at T3 had an adjusted odds ratio for tacrolimus neurotoxicity of 6.3 (95% CI, 1.9-21, P = 0.003). CONCLUSIONS: This data indicates that intraoperative ultrasonic ONSD after reperfusion can predict tacrolimus neurotoxicity after liver transplantation. TRIAL REGISTRATION: NCT03799770; registered on January 1st, 2019.

Norepinephrine boluses for the prevention of post-reperfusion syndrome in living donor liver transplantation: A prospective, open-label, single-arm feasibility trial.

Background and Aims: Post-reperfusion syndrome (PRS) is a serious haemodynamic event during liver transplantation (LT), which increases early graft dysfunction and mortality. This study aimed to test the efficacy and safety of norepinephrine (NE) boluses to prevent PRS during orthotopic LT. Methods: This feasibility phase II trial prospectively recruited a single arm of 40 patients undergoing living donor LT. The intervention was an escalated protocol of NE boluses starting at 20 µg. The primary outcome was the incidence of PRS. The secondary outcomes were arrhythmia, electrocardiographic (EKG) ischaemic changes, mean pulmonary pressure after reperfusion, 3-month survival and 1-year survival. Results: PRS occurred in 28 (70%) cases [95% confidence interval (CI) 54% to 83%, P < 0.001], with a relative risk reduction of 0.22 when compared to our previous results (90%). Twelve cases developed transient EKG ischaemic changes. All EKG ischaemic changes returned to baseline after correction of hypotension. There was no significant arrhythmia or bradycardia (95% CI 0 to 0.9). After reperfusion, the mean pulmonary artery pressure was not significantly higher than the normal limit (20 mmHg) (P = 0.88). The 3-month survival was 0.95 (95% CI 0.83 to 0.99), and the 1-year survival was 0.93 (95% CI 0.8 to 0.98). Conclusion: Our findings suggest that NE boluses starting with 20 µg is feasible and effective in lowering the risk of PRS during living donor LT. Additionally, NE boluses were not associated with significant myocardial ischaemic events, arrhythmia or a rise in pulmonary pressure.

Mannitol for prevention of acute kidney injury after liver transplantation: a randomized controlled trial.

BACKGROUND: Acute kidney injury (AKI) is a common complication after liver transplantation, which is associated with increased morbidity and mortality. Therefore, this study investigated mannitol as an oxygen-free radical scavenger and its role in the prevention of early AKI after living donor liver transplantation (LDLT). METHODS: A total of 84 adult patients who underwent LDLT were randomly assigned to two equal groups: the M group, where patients received 1 g/kg mannitol 20%, or the S group, where patients received an equal volume of saline. The primary outcome was the incidence of early AKI, defined as a 0.3 mg/dl increase in the serum creatinine 48 h postoperatively. Laboratory assessments of the graft and creatinine were recorded until 3 months after transplantation besides the post-reperfusion syndrome and the intraoperative hemodynamic measurements. RESULTS: The AKI incidence was comparable between groups (relative risk ratio of 1.285, 95% CI 0.598-2.759, P = 0.518). Moreover, AKI stages and serum creatinine 3 months after transplantation, P = 0.23 and P = 0.25, respectively. The incidence of the post-reperfusion syndrome was comparable in both groups, 29/39 (74.4%) and 31/41 (75.6%) in M and S groups, respectively, P = 0.897. The intraoperative hemodynamic parameters showed no significant difference between groups using the area under the curve. CONCLUSION: The current LDLT recipient sample was insufficient to demonstrate that pre-reperfusion 1 g/kg mannitol infusion would reduce the risk of early AKI or post-reperfusion syndrome. CLINICAL TRIAL REGISTRATION NUMBER: Pan African Clinical Trials Registry (PACTR202203622900599); https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=21511 .

Atorvastatin for reduction of 28-day mortality in hospitalized COVID-19 patients: study protocol for a randomized, double-blinded, placebo-controlled, clinical trial.

BACKGROUND: Although mass vaccination has reduced the severity of COVID-19, mortality is still high among hospitalized patients. Being a sepsis-like disease, an anti-inflammatory drug as atorvastatin would reduce mortality and severity in COVID-19. METHODS: We designed a randomized clinical trial that recruited 220 COVID-19 patients admitted in the COVID-19 isolation hospital at Mansoura University, Egypt. One hundred ten cases were assigned to receive 40 mg atorvastatin once daily for 28 days, and 110 were assigned to receive placebo. Delta Pharm company supported the study with the drug and the placebo, which mimics the drug as regards the drug package, the tablet color, consistency, and size. All patients received the standard treatment as per the hospital protocol. The Institutional Review Board approval and the informed consent from all participants were obtained. The primary outcome is the 28-day all-cause mortality. Additionally, we will collect the in-hospital mortality, the need for mechanical ventilation, time to clinical improvement, in-hospital thrombo-embolic events, acute kidney injury, and the hospital and the intensive care duration of stay. We plan to follow the patients up for 6 months for reporting mortality and long-term neurological, psychological, and respiratory consequences. We will report the un-adjusted 28-mortality using χ2. Then, we will report the adjusted odds ratio with a pre-planned multiple logistic regression model. We will report our results using the point estimate and the 95% confidence interval and the P-value. DISCUSSION: The additional issue that we would like to discuss is the added workload on the clinicians and the allied healthcare workers who performed research at the time of the pandemic. Therefore, doing research at the pandemic era was, indeed, challenging. TRIAL REGISTRATION: The study was registered at the Clinical Trial Registry ( NCT04952350 ) on July 1st, 2021.