EVALUATION OF HYDROCORTISONE, VITAMIN C, AND THIAMINE FOR THE TREATMENT OF SEPTIC SHOCK: A RANDOMIZED CONTROLLED TRIAL (THE HYVITS TRIAL).

ABSTRACT: Purpose: The aim of the study is to evaluate the effect of combined hydrocortisone, vitamin C, and thiamine (triple therapy) on the mortality of patients with septic shock. Methods : This multicenter, open-label, two-arm parallel-group, randomized controlled trial was conducted in four intensive care units in Qatar. Adult patients diagnosed with septic shock requiring norepinephrine at a rate of ≥0.1 µg/kg/min for ≥6 h were randomized to a triple therapy group or a control group. The primary outcome was in-hospital mortality at 60 days or at discharge, whichever occurred first. Secondary outcomes included time to death, change in Sequential Organ Failure Assessment (SOFA) score at 72 h of randomization, intensive care unit length of stay, hospital length of stay, and vasopressor duration. Results: A total of 106 patients (53 in each group) were enrolled in this study. The study was terminated early because of a lack of funding. The median baseline SOFA score was 10 (interquartile range, 8-12). The primary outcomes were similar between the two groups (triple therapy, 28.3% vs. control, 35.8%; P = 0.41). Vasopressor duration among the survivors was similar between the two groups (triple therapy, 50 h vs. control, 58 h; P = 0.44). Other secondary and safety endpoints were similar between the two groups. Conclusion: Triple therapy did not improve in-hospital mortality at 60 days in critically ill patients with septic shock or reduce the vasopressor duration or SOFA score at 72 h. Trial Registration:ClinicalTrials.gov identifier: NCT03380507. Registered on December 21, 2017.

Anticoagulation in critically ill patients on mechanical ventilation suffering from COVID-19 disease, The ANTI-CO trial: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To assess the effect of anticoagulation with bivalirudin administered intravenously on gas-exchange in patients with COVID-19 and respiratory failure using invasive mechanical ventilation. TRIAL DESIGN: This is a single centre parallel group, superiority, randomized (1:1 allocation ratio) controlled trial. PARTICIPANTS: All patients admitted to the Hamad Medical Corporation -ICU in Qatar for COVID-19 associated respiratory distress and in need of mechanical ventilation are screened for eligibility. INCLUSION CRITERIA: all adult patients admitted to the ICU who test positive for COVID-19 by PCR-test and in need for mechanical ventilation are eligible for inclusion. Upon crossing the limit of D-dimers (1.2 mg/L) these patients are routinely treated with an increased dose of anticoagulant according to our local protocol. This will be the start of randomization. EXCLUSION CRITERIA: pregnancy, allergic to the drug, inherited coagulation abnormalities, no informed consent. INTERVENTION AND COMPARATOR: The intervention group will receive the anticoagulant bivalirudin intravenously with a target aPTT of 45-70 sec for three days while the control group will stay on the standard treatment with low-molecular-weight heparins /unfractionated heparin subcutaneously (see scheme in Additional file 1). All other treatment will be unchanged and left to the attending physicians. MAIN OUTCOMES: As a surrogate parameter for clinical improvement and primary outcome we will use the PaO2/FiO2 (P/F) ratio. RANDOMISATION: After inclusion, the patients will be randomized using a closed envelope method into the conventional treatment group, which uses the standard strategy and the experimental group which receives anticoagulation treatment with bivalirudin using an allocation ratio of 1:1. BLINDING (MASKING): Due to logistical and safety reasons (assessment of aPTT to titrate the study drug) only the data-analyst will be blinded to the groups. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): We performed a sample size calculation and assumed the data for P/F ratio (according to literature) is normally distributed and used the mean which would be: 160 and SD is 80. We expect the treatment will improve this by 30%. In order to reach a power of 80% we would need 44 patients per group (in total 88 patients). Taking approximately 10% of dropout into account we will include 100 patients (50 in each group). TRIAL STATUS: The local registration number is MRC-05-082 with the protocol version number 2. The date of approval is 18th June 2020. Recruitment started on 28th June and is expected to end in November 2020. TRIAL REGISTRATION: The protocol is registered before starting subject recruitment under the title: "Anticoagulation in patients suffering from COVID-19 disease. The ANTI-CO Trial" in ClinicalTrials.org with the registration number: NCT04445935 . Registered on 24 June 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 2). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Evaluation of the risk of acute kidney injury with the use of piperacillin/tazobactam among adult critically ill patients.

PURPOSE: Piperacillin/tazobactam (PT), when combined with vancomycin, is associated with an increased risk of acute kidney injury (AKI). It is not known whether PT alone is associated with a higher incidence of AKI compared to other ß-lactams among critically ill patients. The objective of this study was to compare the incidence of AKI associated with the use of PT to other ß-lactams among adult critically ill patients METHODS: This retrospective study was conducted in the surgical and the medical intensive care units at two hospitals within Hamad Medical Corporation (HMC) in Qatar and included adult critically ill patients who received at least one dose of anti-pseudomonal ß-lactams. The primary outcome was acute kidney injury, defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Multiple logistic regression with adjustment for pre-specified potential confounders was used for the primary outcome analysis. RESULTS: A total of 669 patients were included in the analysis: 507 patients in the PT group and 162 patients in the control (meropenem/cefepime) group. AKI occurred in 136 (26.8%) members of the PT group and 38 (23.5%) members of the control group [odds ratio (OR) 1.2; 95% confidence interval (CI) 0.79-1.8]. The results were not significantly altered after adjusting for the pre-specified potential confounders (adjusted OR 1.38; 95% CI 0.88-2.15). CONCLUSION: In this study, PT was not associated with a higher risk of AKI compared to cefepime or meropenem among adult critically ill patients.

Community Acquired Urosepsis: A surgical intensive care Experience.

Urosepsis contributes significantly to the epidemiology of sepsis. Urosepsis can be classified as community acquired or hospital acquired, depending upon the origin of infection acquisition: either from the community or from a healthcare facility. A great deal of literature is available about nosocomial urosepsis, but the literature regarding community-acquired urosepsis (CAUs) is limited, and studies are underpowered. The aim of our study was to determine the epidemiology, bacteriology, severity, and outcome of CAUs. Methods and Patients: All patients admitted from the emergency department to the surgical intensive care unit (SICU) with urosepsis over a period of 10 years were identified and included retrospectively from the SICU registry. The study was retrospective. Data were entered into the SPSS program version 23, and groups were compared by using chi-square and t-tests. Results were considered statistically significant at p ≤ 0.05. Results: During the study period, 302 patients with CAUs were admitted to the SICU. The common etiology was obstructive uropathy (60%). The Local Arab population outnumbered the non-Arab population (164/54.3%), and there were equal numbers of patients of both genders. Diabetes mellitus and hypertension together were the common comorbidities. Seventy-five percent of patients had acute kidney injury (AKI). Thirty-eight percent of patients had percutaneous nephrostomy, and 24.8% of patients underwent endoscopic stent insertion to relieve the obstruction. Ninety-three percent of patients were admitted with septic shock, and 71.5% had bacteremia. The common bacteria (36.1%) was extended-spectrum beta-lactamase-(ESBL)-producing bacteria, with a predominance of Escherichia coli (31.5%). Fifty-four percent of patients required a change of antibiotics to carbapenem. Eighty-two percent of patients had acute respiratory distress syndrome (ARDS). Patients with bacteremia had a statistically significant AKI, ARDS, and septic shock (p < 0.001). Male patients had a significantly higher incidence of oliguria, intubation, and ARDS (p < 0.05). Eight patients died of urosepsis during the study period, giving a mortality rate of 2.6%. Conclusion: In our patients, obstruction of urine flow was the most common cause of CAUs. Our urosepsis patients had a higher bacteremia rate, which led to higher incidences of organ dysfunction and septic shock. ESBL bacteria were a frequent cause of urosepsis, requiring a change of the initial antibiotic to carbapenem. Male patients had a significantly higher rate of organ dysfunction. Mortality in our urosepsis patients was lower than mentioned in the literature.

Optimal dose and duration of enteral erythromycin as a prokinetic: A surgical intensive care experience.

BACKGROUND: Enteral feeding has various advantages over parenteral feeding in critically ill patients. Acutely ill patients are at risk of developing enteral feeding intolerance. Prokinetic medications improve gastrointestinal mobility and enteral feed migration and absorption. Among the available prokinetic agents, erythromycin is the most potent. Erythromycin is used in different dosages and durations with variable efficacy. Intravenous erythromycin has an early and high rate of tachyphylaxis; hence, enteral route is preferred. Recently, the combination of prokinetic medications has been increasingly used because they accelerate the prokinetic action and decrease the adverse effects. AIM: This study aimed to determine the optimal effective prokinetic dose and duration of administering enteral erythromycin in combination with metoclopramide in critically ill patients. PATIENTS AND METHODS: This study has a prospective observation design. After obtaining permission from the medical research center of the institution, all patients in the surgical and trauma intensive care unit having enteral feed intolerance and those who were already on metoclopramide for 24 hour (h) were enrolled in the study. Patients' demographic data, diagnosis, surgical intervention, disease severity scores, erythromycin dose, duration of administration, any adverse effects, factors affecting erythromycin response, and outcome were recorded. All patients received 125 mg syrup erythromycin twice daily through a nasogastric tube (NGT). The NGT was clamped for 2 h, and half amount of previous enteral feeds was resumed. If the patient did not tolerate the feeds, the erythromycin dose was increased every 24 h in the increment of 250, 500, and 1000 mg (Figure 1). Statistical significance was considered at P <  0.05. A total of 313 patients were enrolled in the study. Majority of the patients were male, and the mean age was 45 years. RESULTS: Majority (48.2%) of the patients (96) with feed intolerance were post laparotomy. Ninety percent (284) of the patients responded to prokinetic erythromycin therapy, and 54% received lower dose (125 mg twice daily). In addition, 14% had diarrhea, and none of these patients tested positive for Clostridium difficile toxin or multidrug resistance bacteria. The mean duration of erythromycin therapy was 4.98 days. The most effective prokinetic dose of erythromycin was 125 mg twice daily (P = 0.001). Erythromycin was significantly effective in patients with multiple organ dysfunction and shock (P = 0.001). Patients with high disease severity index and multiple organ dysfunction had significantly higher mortality (p < 0.05). Patients not responding to erythromycin therapy also had a significant higher mortality (p = 0.001). CONCLUSION: Post-laparotomy patients had high enteral feed intolerance. Enteral erythromycin in combination with metoclopramide was effective in low dose and was required for short duration. Patients who did not tolerate feeds despite increasing dose of erythromycin had higher mortality.

Dry Beriberi Due to Thiamine Deficiency Associated with Peripheral Neuropathy and Wernicke's Encephalopathy Mimicking Guillain-Barré syndrome: A Case Report and Review of the Literature.

BACKGROUND Beriberi due to thiamine (vitamin B1) deficiency has two clinical presentations. Patients with dry beriberi present with neuropathy, and patients with wet beriberi present with heart failure, with or without neuropathy. Dry beriberi can mimic the most common form of Guillain-Barre syndrome (GBS), an acute inflammatory demyelinating polyradiculoneuropathy (AIDP). Severe thiamine deficiency results in Wernicke's encephalopathy. This report of a case of dry beriberi and Wernicke's encephalopathy due to thiamine deficiency includes a review of the literature. CASE REPORT A 56-year old woman with a history of gallstone pancreatitis and protein-calorie malnutrition was treated six months previously with total parenteral nutrition (TPN). She initially presented at another hospital with paresthesia of the lower limbs, arms, and neck, and symptoms of encephalopathy. Initial diagnosis of GBS was made, based on magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) findings. Despite five days of intravenous immunoglobulin (IVIG) treatment, her encephalopathy worsened, requiring transfer to our hospital, where she required intubation and treatment with vasopressors. A repeat MRI of her brain showed changes consistent with Wernicke's encephalopathy. Following treatment with high-dose intravenous thiamine, her mental status improved within 48 hours, and by the third hospital day, she no longer required intubation. CONCLUSIONS Symptoms and signs of dry beriberi due to thiamine deficiency can mimic those of acute or chronic GBS. However, thiamine repletion leads to rapid clinical improvement and can prevent irreversible neurologic sequelae, including Korsakoff syndrome. Clinicians should consider thiamine deficiency in malnourished patients presenting with symptoms and signs of GBS.

A Survey on the Awareness and Attitude of Physicians on Direct Oral Anticoagulants in Qatar.

Direct oral anticoagulants (DOACs) are more commonly prescribed since their introduction. Reports on inappropriate prescribing have been observed which may indicate poor awareness on these agents. In this study, we aim to evaluate the extent of the physicians' knowledge on DOACs and its possible impact on physicians' confidence to prescribe these medications. A prospective cross-sectional survey was developed based on the literature review. Eligible participants were physicians and surgeons currently practicing at Hamad General Hospital in Qatar. The survey included questions on demographic and professional characteristics. It also evaluated the awareness and attitudes regarding safety, efficacy, and prescribing of DOACs. Over 6-month period, 175 practitioners responded to the survey. Overall awareness score was moderate (61% ± 18%). These scores were in alignment with participants' self-satisfaction with knowledge on DOACs (66% were not satisfied) and participants' confidence toward prescribing DOACs (48% were not confident). Age, degree of education, and years of experience had significant positive influence on awareness score. This survey indicates that practitioners have moderate awareness on DOACs. Future work should focus on reassessing practitioners' knowledge after providing well-designed education campaigns.