Outcomes of a Pilot Contribution Database for the ICU Pharmacy Team at the University Hospitals of Leicester NHS Trust

Introduction It has long been felt that many contributions made by the ICU Pharmacy team, are not well showcased by the yearly regional network multi-speciality contributions audit. Themes specific to ICU are diluted amongst Trust and region wide data, and valuable learning for the multi-disciplinary team (MDT) is subsequently overlooked. Objective(s): The aims of this project were to: * Develop and pilot a MicrosoftTM Access © database for the ICU pharmacy team to record significant contributions. * Enable the production of reports to the ICU Quality & Safety board, to raise awareness, disseminate concerns, and influence future quality improvement projects. * Provide examples to contribute to the training of the whole MDT. * Generate evidence of team effectiveness and encourage further investment. * Provide team members with a means to recall contributions, for revalidation, appraisal, prescribing re-affirmation and framework mapping. Method(s): * A database was built with a user-friendly data-entry form to prevent overwriting. Fields were agreed with peers who would be using the database. * The team were invited to voluntarily enter their contributions which they thought added value and provided useful learning. * The pilot phase ceased with the emergence of the Omicron SARS-CoV-2 variant, due to staffing pressures and surge planning. Result(s): * Between 12/07/2021 and 25/11/2021, a total of 211 contributions were recorded. * Pharmacists entered 88.6% and a single technician entered 11.4% of these. * Independent Prescribing was utilised in 52.13% of contributions, and deprescribing in 25.12%. * Figure 1 demonstrates the contributions by drug group * The top 5 drugs associated with contributions were: ? Dalteparin ? Vancomycin ? Voriconazole ? Meropenem ? Co-trimoxazole * Treatment optimisation was an outcome for 76.3% of all contributions. Figure 2 stratifies these by type. Contributions. * Drug suitability was a cause for intervention in 12.8% of all contributions, encompassing allergies, contraindications, cautions and interactions and routes. * Medicines reconciliation accounted for 17.54% of all contributions, which almost half were Technician led. Admission was the most common stage to intervene (81.08%), followed by transcription. * Of all contributions, 37.91% were classified as patient safety incidents. Reassuringly 76.25% of these were prevented by the Pharmacy team. Themes have been extracted from these incidents and are presented in Table 1. Conclusion(s): PROTECTED-UK1 demonstrated the value pharmacists contribute to the quality and safety of patient care on ICU. Studies of similar quality and scale including Pharmacy Technicians are lacking, but even in this pilot study, it is evident how important their input is. Independent prescribing is a fundamental and well utilised part of our ICU Pharmacist skillset, supporting the GPICS2 recommendation that ICU pharmacists should be encouraged to become prescribers. Compiling a team interventions database is a useful tool to highlight local priority areas for guideline development;training;and ensuring that appropriate decision support is built into electronic prescribing systems. To improve the usefulness of the data, further stratification of contributions according to the Eadon Criteria3 may be worthwhile, to expand its use as a medication safety thermometer for ICU.

COVID-19 in a patient with Good's syndrome and in 13 patients with common variable immunodeficiency

Antibody deficiencies constitute the majority of primary immunodeficiencies in adults. These patients have a well-established increased risk of bacterial infections but there is a lack of knowledge regarding the relative risks upon contracting COVID-19. In this monocentric study the disease course of COVID-19 in 1 patient with Good's syndrome and in 13 patients with common variable immunodeficiency (CVID) is described. The severity of disease ranged from very mild to severe. Several patients required hospitalization and immunomodulatory treatment but all survived. Although viral infections are not a typical feature of humoral immunodeficiencies we recommend that vigilance is increased in the management of patients with Good's syndrome and CVID during the COVID-19 pandemic.Copyright © 2021

Incidence of venous thrombo-embolism in SARS COVID-19 in a district general critical care unit

Introduction: SARS COVID-19 is known to produce a hypercoagulable state in which micro and macro-thrombi form, leading to reduced arterial oxygen saturation, organ failure, and increased need for mechanical ventilation - all of which increase mortality. Currently there is conflicting evidence regarding the efficacy of heparin anticoagulation on the incidence of venous thrombo-embolism (VTE) in COVID-19 and throughout the pandemic clinical guidance for heparin use has been updated from standard to intermediate dosing for thromboprophylaxis. Studies show rates of 21-31%1,2 for symptomatic VTE in ICU COVID-19 patients receiving standard dose prophylactic dalteparin. Objectives: This service evaluation presents local data on incidence of VTE and mortality in critical care COVID-19 patients and provides a summary discussion of the latest trials on prevention of VTE in COVID-19 and their recommendations. Methods: A retrospective evaluation was undertaken on patients admitted to Barnsley Hospital Critical Care Unit during March - December 2020 with confirmed COVID-19 during wave one (27/03/20 - 14/06/20) and wave two (15/06/20 - 03/ 12/20) of the pandemic. The primary outcome was incidence of VTE, which was defined by either: D-dimer ≥ 3 mg/L;a positive ultrasound doppler (USS);or by computed tomography pulmonary angiography (CTPA). Mortality data was also collected. Results: Data was collected on 96 patients (n=73 male, n=23 female). VTE occurred in 30.2% of patients with n=14 confirmed by CTPA, n=1 confirmed by USS, and n=15 with D-dimer ≥ 3 mg/L (but not already confirmed by CTPA or USS). Male and female mortality in the intubated group for both waves was 58.3% and 56.0% respectively. Between waves one and two there was a 28% decrease in mortality across all patients, a 27% decrease in the rate of intubation, and a 20% decrease in mortality in the intubated-only population. Mortality across both waves in the standard and intermediate dalteparin dose populations was 67% and 19% respectively. Table 1 summarises mortality data for the different sub-populations. Conclusion: Our data shows a VTE rate consistent with the literature. Statistical analysis of the data was undertaken using Fisher's exact test. Overall mortality between waves one and two was not significantly different at the P<0.05 level. Reduction in mortality across both waves in the standard and intermediate dose dalteparin populations was significant at the P<0.01 level. However, due to advances in care developed throughout the pandemic, we cannot say if the reduction in mortality is due to the use of intermediate dose dalteparin, as there are other factors to consider. Despite this, its use, combined with other treatments, is consistent with an improved outcome in COVID-19 ICU patients. Current best evidence from INSPIRATION and REMAP-CAP/ATTACC/ACTIV-4a trials3,4 recommends giving treatment dose low-molecular-weight heparin (LMWH) to all COVID-19 hospitalised patients, but to reduce to intermediate dose if admitted to critical care/ICU providing there is no evidence of VTE, as defined above. Trials currently show no benefit of routine treatment dose dalteparin over intermediate dose in critical care for COVID-19 patients.

2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19

The International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. Key recommendations (grade 1A or 1B) include: (1) low-molecular-weight heparins (LMWHs) for the initial (first 10 days) treatment and maintenance treatment of cancer-associated thrombosis;(2) direct oral anticoagulants for the initial treatment and maintenance treatment of cancer-associated thrombosis in patients who are not at high risk of gastrointestinal or genitourinary bleeding, in the absence of strong drug-drug interactions or of gastrointestinal absorption impairment;(3) LMWHs or direct oral anticoagulants for a minimum of 6 months to treat cancer-associated thrombosis;(4) extended prophylaxis (4 weeks) with LMWHs to prevent postoperative venous thromboembolism after major abdominopelvic surgery in patients not at high risk of bleeding;and (5) primary prophylaxis of venous thromboembolism with LMWHs or direct oral anticoagulants (rivaroxaban or apixaban) in ambulatory patients with locally advanced or metastatic pancreatic cancer who are treated with anticancer therapy and have a low risk of bleeding.

Effects of dalteparin on anti-Xa activities cannot be predicted in critically ill COVID-19 patients.

Critically ill COVID-19 patients are at high risk of thromboembolic events despite routine-dosed low-molecular-weight heparin thromboprophylaxis. However, in recent randomized trials increased-intensity thromboprophylaxis seemed futile and possibly even harmful. In this explorative pharmacokinetic (PK) study we measured anti-Xa activities on frequent timepoints in 15 critically ill COVID-19 patients receiving dalteparin and performed PK analysis by nonlinear mixed-effect modelling. A linear one-compartment model with first-order kinetics provided a good fit. However, wide interindividual variation in dalteparin absorption (variance 78%) and clearance (variance 34%) was observed, unexplained by routine clinical covariates. Using the final PK model for Monte Carlo simulations, we predicted increased-intensity dalteparin to result in anti-Xa activities well over prophylactic targets (0.2-0.4 IU/mL) in the majority of patients. Therapeutic-intensity dalteparin results in supratherapeutic anti-Xa levels (target 0.6-1.0 IU/mL) in 19% of patients and subtherapeutic levels in 22%. Therefore, anti-Xa measurements should guide high-intensity dalteparin in critically ill COVID-19 patients.

A case of granulomatosis with polyangiitis complicated by COVID-19: Challenges in diagnosis and management

Case report-IntroductionGranulomatosis with Polyangiitis (GPA) is a rare small-to medium-vessel vasculitis associated with anti-neutrophil cytoplasmic autoantibody (ANCA). Its multi-systemic features include pulmonary, ear, nose, and throat (ENT), renal, and neurological manifestations. Its incidence is estimated to be 10.2 cases per million population. It is challenging to diagnose when its symptoms are treated in isolation from one another. This case highlights the difficulty in diagnosing GPA in a patient with respiratory symptoms during the Coronavirus Disease 2019 (COVID-19) pandemic and describes the challenges of managing it in the context of a subsequent COVID-19 infection as the mainstay of treatment remains immunosuppression.Case report-Case descriptionA 78-year-old female non-smoker with a history of leg ulcers developed a 3-month history of cough and haemoptysis and was treated in primary care for suspected sinus and chest infections. She then presented to Accident and Emergency twice for the same symptoms and was discharged after having her antibiotics changed.2 weeks later, she presented for the third time with cough, ongoing haemoptysis, conjunctivitis in the right eye, pain over the right side of her head, and discharge from her right ear. She was admitted as she was pyrexical, tachycardic and her CRP was 60. COVID-19 swabs were negative. ENT team recommended IV ceftriaxone and metronidazole for suspected orbital cellulitis. Blood cultures remained negative. CT sinuses with contrast showed right sided thrombosis of transverse sinus and bilateral mastoid effusion of the middle ear. Following neurology review, she was anticoagulated with dalteparin. A day later, she was transferred to the Respiratory ward and dropped her Haemoglobin level to 70. Her chest radiograph showed diffuse alveolar haemorrhage and CT images showed widespread bilateral peri-hilar consolidation.A rheumatology opinion was sought and vasculitic screen showed ANCA 268, and PR3 >177. Her urinary protein/creatinine ratio was elevated at 90. Rheumatology team confirmed multi-systemic GPA and recommended starting oral Prednisolone 60 mg daily. After the renal team was consulted, she was moved to a side-room and started on IV Methylprednisolone (pulsed with three doses), along with cyclophosphamide and rituximab. Dalteparin was discontinued.2 days later, she desaturated, and became pyrexical. Repeat COVID-19 swabs were positive.Three Consultants agreed that Plasma Exchange and Non-Invasive Ventilation (NIV) would be inappropriate. A Do Not Attempt Resuscitation form was signed, and prognosis was discussed with the patient and her 78-year-old husband who requested to visit. Patient deteriorated and unfortunately died 6 days later.Case report-DiscussionThis case is interesting because it highlights the diagnostic challenge of GPA. Retrospectively, it may be noted that doctors persisted in treating suspected infection although the patient continued to deteriorate. However, a diagnosis should be re-considered if the patient does not respond to treatment and it is important to consider vasculitis as a cause of haemoptysis.Anticoagulation was started since the benefits were considered to outweigh the risks as her haemoptysis was of small volume. The patient soon developed pulmonary haemorrhage, so the risks of anticoagulation should not be underestimated in vasculitis.The Rheumatology team's cautious approach to immunosuppression was in stark contrast to the renal team's aggressive approach. The Renal team believed that concerns about protecting the patient from COVID-19 when she was negative from this infection should not take precedence over appropriate immunosuppression from a potentially fatal vasculitis.The patient was admitted at the start of the COVID-19 pandemic and was negative for COVID-19 on admission. She was nursed in a bay on the Respiratory ward where she later became COVID-19 positive. This raises questions about whether the earlier test was a false negative result or whether her infection was hospital-acquired. Infection cont ol guidelines were changing rapidly at the start of the COVID-19 pandemic.The decision to avoid plasma exchange was based on the findings of the PEXIVAS trial. NIV was avoided as it required a full-face mask to minimize particle dispersion but would pose an asphyxiation risk as patient was coughing up blood.Finally, the team learnt to be flexible in these extraordinary circumstances when dealing with the end-of-life decisions of the COVID-19 positive patient. Although her husband was a vulnerable person because of his age, he was given the opportunity to visit while wearing Personal Protective Equipment and agreed to self-isolate for two weeks.Case report-Key learning pointsThis case helped me appreciate the complexity of deciding to immunosuppress an already severely ill patient in the context of the COVID-19 pandemic. I recognised that the patient had a poor prognosis with or without immunosuppression and our role as healthcare professionals was to give her the best chance of recovery. The conference will allow me to interact with other colleagues and discuss what they would do in this situation as our Rheumatology and Renal teams had different approaches.After further reading on false negative results, we found that Johns Hopkins researchers found that testing people for SARS-CoV2 too early in the course of infection is likely to result in a false negative test even though they may eventually test positive for the virus.I have also learnt about the PEXIVAS trial which found that the addition of plasma exchange to standard therapy does not reduce the risk for all-cause mortality among patients with severe ANCA-associated vasculitis. Moreover, a reduced-dose regimen of glucocorticoids is non-inferior to a standard-dose protocol, while reducing the risk for serious infections.Diffuse alveolar haemorrhage (DAH) is not treatable with arterial embolization or bronchoscopic methods due to the diffuse nature of the bleeding. Extracorporeal membrane oxygenation (ECMO) has been used to support patients with DAH but the use of ECMO is controversial due to the need for anticoagulation.The conference will help me deepen my understanding of epidemic rheumatology which will be useful for my clinical practice going forward, especially if there is a second wave of the COVID-19 pandemic. I am keen to use this event to engage with other clinicians on immunosuppression in the context of infection so that I may confidently manage similarly complex cases in the future.