INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP): Protocol and statistical analysis plan for an investigator-initiated international metatrial of randomised studies.

AIMS: Inhaled nebulised unfractionated heparin (UFH) has a strong scientific and biological rationale that warrants urgent investigation of its therapeutic potential in patients with COVID-19. UFH has antiviral effects and prevents the SARS-CoV-2 virus' entry into mammalian cells. In addition, UFH has significant anti-inflammatory and anticoagulant properties, which limit progression of lung injury and vascular pulmonary thrombosis. METHODS: The INHALEd nebulised unfractionated HEParin for the treatment of hospitalised patients with COVID-19 (INHALE-HEP) metatrial is a prospective individual patient data analysis of on-going randomised controlled trials and early phase studies. Individual studies are being conducted in multiple countries. Participating studies randomise adult patients admitted to the hospital with confirmed SARS-CoV-2 infection, who do not require immediate mechanical ventilation, to inhaled nebulised UFH or standard care. All studies collect a minimum core dataset. The primary outcome for the metatrial is intubation (or death, for patients who died before intubation) at day 28. The secondary outcomes are oxygenation, clinical worsening and mortality, assessed in time-to-event analyses. Individual studies may have additional outcomes. ANALYSIS: We use a Bayesian approach to monitoring, followed by analysing individual patient data, outcomes and adverse events. All analyses will follow the intention-to-treat principle, considering all participants in the treatment group to which they were assigned, except for cases lost to follow-up or withdrawn. TRIAL REGISTRATION, ETHICS AND DISSEMINATION: The metatrial is registered at ClinicalTrials.gov ID NCT04635241. Each contributing study is individually registered and has received approval of the relevant ethics committee or institutional review board. Results of this study will be shared with the World Health Organisation, published in scientific journals and presented at scientific meetings.

Comparison Between Ultrasound-guided Caudal Analgesia versus Peripheral Nerve Blocks for Lower Limb Surgeries in Pediatrics: A Randomized Controlled Prospective Study.

Background and Aim: Ultrasound (US) guided regional analgesia is a safe and effective method in providing perioperative analgesia in pediatrics with a high success rate rapid onset and fewer side effects. The aim of this study was to compare the efficacy of US-guided caudal block versus US-guided peripheral nerve blocks (femoral and sciatic nerve blocks) in providing perioperative analgesia in pediatrics undergoing unilateral lower limb surgery. Methods: Children aged 1-12 years scheduled for unilateral lower limb surgery during the period from January 2020 to December 2021 were randomly allocated into two groups. Group C where pediatrics received US-guided caudal block, while in group P, pediatrics received US-guided femoral and sciatic nerve blocks after the induction of general anesthesia (GA). The primary aim was to compare the postoperative pain (evaluated by the COMFORT pain score) between the two groups. Secondary aims were to compare perioperative opioids used parents' satisfaction and occurrence of side effects. Results: Pediatrics who underwent unilateral lower limb surgeries were allocated into two groups (group C and group P). There was no significant difference between patients' baseline characteristics and the postoperative pain score at 2, 4, 16, and 20 h.' However there was a statistical significance at 6, 8, 12, and 24 h postoperatively, frequency of analgesia as well as the total postoperative dose of opiates (nalbuphine). Time to first analgesic (nalbuphine) requirement was significantly less in group C with a mean of (9.6±2.9 h) than in group P with a mean of (15.1±3.5 h). Parents of children in group P were more satisfied than those in group C with no recorded complications for both techniques. Conclusion: US-guided lower limb peripheral nerve block is a simple and safe method to provide adequate and more prolonged analgesia compared to US-guided caudal block for lower limb surgeries in pediatrics.

The Shikani Optical Stylet as an Alternative to Awake Fiberoptic Intubation in Patients at Risk of Secondary Cervical Spine Injury: A Randomized Controlled Trial.

BACKGROUND: Conventional intubation of the trachea and consequent prone positioning of anesthetized patients with cervical spine instability may result in secondary neurological injury. Historically, flexible fiberoptics used to be the chief choice for patients presenting with cervical spine instability surgery with difficult airway. Recently, the rigid optical stylets have shown promise in assisting difficult intubations. PURPOSE: The aim of the present study was to compare the efficacy of Shikani optical stylet (SOS) with the flexible fiberscope for awake intubation in patients with cervical spine instability. PATIENTS AND METHODS: In total, 60 adult patients diagnosed with cervical instability or at risk of secondary cervical injury, who were planned for awake intubation and/or self-positioning prone, were registered in this study and were randomly categorized into 2 equal groups (30 patients each), a fiberoptic group and an SOS group, followed by assessment of coughing and gagging during intubation, time to successful intubation, number of attempts for successful intubation, and hemodynamic parameters. RESULTS: As regards time to successful intubation, statistically significant differences were detected between the 2 studied groups, with the fiberoptic group having significantly longer intubation time than the Shikani group, whereas no statistically significant differences were recorded between the 2 groups with regard to the first-attempt success, the mean heart rate value, the mean arterial blood pressure, coughing, and occurrence of complications. CONCLUSION: This study validates the efficacy of both SOS and flexible fiberoptic bronchoscope for awake oral intubation in patients with cervical spine instability. SOS has been found to be more effective in reducing time to intubation.

Novel urinary biomarkers and the early detection of acute kidney injury after open cardiac surgeries.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiac surgery, recently, several biomarkers have been used to facilitate early detection of AKI, including Neutrophil-gelatinase-associated-lipocalin (NGAL) and Kidney-injury-molecule-1 (KIM-1).This study was carried out to study the efficacy of urinary KIM-1 and NGAL separately and in combination in relation to early detection and assessment of severity of AKI after cardiac surgeries. METHODS: This prospective study was carried out on 45 adult patients, of both sexes, Cleveland score(CCS) (0-5) and scheduled for elective coronary artery bypass graft (CABG) surgery in Alexandria Main University Hospital, after approval of the ethical committee and having an informed written consent from every patient. Patients were screened for renal function tests before surgery and every day for 3 day after surgery. Freshly urine samples were taken from all patients and centrifuged for microscopic examination of the sediment: preoperative, 2, 12, 24, and 48 hr after cardiopulmonary bypass (CPB) and for measurement of NGAL and KIM-1; after induction, 2, 6, 12, and 24 hr after CPB. The primary end point was the incidence of AKI defined by the AKIN criteria of serum creatinine. RESULTS: 11 patients developed AKI. Patients with AKI had a higher AKIN stages and CCS. CPB time and cross clamp time were significantly higher in the AKI group with a mean of (90.5±16.2) and (60.9±8.1) minutes respectively. Serum creatinine started to be significantly higher in AKI group from the second postoperative day with a mean value of 1.56±0.28 mg/dl compared to a mean value of 0.85±0.14 mg/dl in non-AKI group. Urine sediment score(USS) 1 and 2 were higher in the AKI group than in the non-AKI group 2 hrs after CPB and till the end of the 2nd day with area under the curve (AUC) average of (0.865). Urinary NGAL significantly rise in AKI patients 2 and 6 hr after CPB with corresponding AUC of (0.710 and 0.700) but uKIM-1 was higher in the AKI group 12 and 24 hr after CPB with AUC (0.725 and 0.703) respectively. Combination of urinary NGAL, KIM-1, and USS yielded AUC of 0.906. CONCLUSIONS: urinary NGAL is early sensitive but KIM-1which appears later than but is a more specific biomarker to ischemic renal injury. Urinary microscopic examination was found to be with very high sensitivity and specificity and injury site informative. The combination of more than one biomarker increases the accuracy of early detection of AKI after cardiac surgery.