A Rare Occurrence of Hyperkalemia Following Remdesivir: A Case Series

Remdesivir is a nucleoside analog with broad-spectrum antiviral activity against several viruses such as respiratory syncytial virus, Nipah virus, Ebola virus (EBOV), Middle East respiratory syndrome (MERS-CoV), and Severe Acute respiratory Syndrome Coronavirus-1 (SARS-CoV-1). Remdesivir has been used in moderate to severe COVID-19 during the pandemic. Remdesivir is associated with various adverse drug reactions like serum transaminase elevation, nausea, diarrhea, vomiting, poor appetite, gastroparesis, pneumothorax, hypotension, hematuria etc. It has been rarely associated with hyperkalemia. We have reported 3 cases of hyperkalemia following Remdesivir use. In all 3 cases, patients did not have any renal pathology or history of alcohol consumption. Patients were not taking any concurrent medication which increases serum potassium levels with such characteristics seen in our cases. Temporal association was present between hyperkalemia and initiation of Remdesivir in all cases described. Hence, it is very important to be vigilant while prescribing Remdesivir in COVID-19.

Unexpected acute pulmonary embolism in an old COVID-19 patient with warfarin overdose: a case report

Background Severe acute respiratory syndrome coronavirus 2 disease is strongly associated with a high incidence of thrombotic events. Anticoagulation could be a cornerstone in successfully managing severe forms of coronavirus disease 2019 (COVID-19). However, optimal anticoagulant dosing in elderly patients is challenging because of high risk of both thrombosis and bleeding. Case summary We present here the case of an 89-year-old patient receiving warfarin for atrial fibrillation and valvular heart disease, admitted to the intensive care unit for respiratory failure due to COVID-19. The patient presented with a severe epistaxis associated with warfarin overdose [international normalized ratio (INR) > 10]. After a successful initial reversal using vitamin K per os, INR values greatly fluctuated up to 10, requiring repeated administrations of vitamin K. Despite starting low-molecular-weight heparin therapy at therapeutic dose as soon as INR value was below 2.0, the patient further developed an acute bilateral and proximal pulmonary embolism concomitantly with a sharp D-dimer increase. The combination of azithromycin intake, a known inhibitor of CYP2C9, with the presence of CYP2C9*2 and −1639G>A VKORC1, two variants associated with warfarin hypersensitivity, have likely contributed to explain the warfarin overdose and the difficulty to reverse warfarin effect in this patient. Discussion This case report illustrates the complexity of COVID-19 pathophysiology and its management for physicians, especially in patients receiving vitamin K antagonists (VKAs). Infection, concurrent medication use, and pharmacogenetic factors involved in VKA metabolism and pharmacodynamics may lead to a loss of control of anticoagulation. Pulmonary embolism should still be considered in COVID-19 patients even with effective or overdosed anticoagulant therapy.

Diabetic Ketoacidosis Management and Treatment Outcome at Medical Ward of Shashemene Referral Hospital, Ethiopia: A Retrospective Study

Background: Diabetic Ketoacidosis (DKA) is the most common and yet potentially life-threatening acute complication of diabetes that progresses rapidly to death and requires immediate medical intervention. Objective: To assess the DKA management and treatment outcome/in-hospital mortality and its predictors among hospitalized patients with DKA at the Medical ward of Shashemene Referral Hospital (SRH). Method: A retrospective study was conducted at the Medical Ward of SRH from 01 February 2015 to 31 January 2017. A systematic random sampling technique was used to select study subjects based on the inclusion criteria. Thus, of 236 reviewed charts, only 225 patients with DKA fulfilled inclusion criteria. Treatment outcome was considered good for patients who have shown improvement at discharge, while poor for patients who left against medical advice or died in the hospital. Logistic regression analysis was done to determine independent predictors for treatment outcome/in-hospital mortality using SPSS version 20 with statistical significant at P ⩽ .05. Results: Of 225 patients with DKA, 124 (55.1%) were male. Regular insulin was prescribed to all patients and antibiotics were administered to 87 (38.7%). Potassium supplementation was given only for 28 (12.4%). Non-adherence to insulin treatment (n = 91; 40.4%) and infection (n = 66; 29.3%) were the principal DKA precipitating factors. Even though 73.8% of hospitalized patients with DKA have shown good treatment outcomes, DKA contributed 12% in-hospital mortality. The result of multivariate logistic regression analysis shown that hypoglycemia is the only independent predictor for in-hospital mortality[ P = .03]. Moreover, the independent predictors for poor DKA treatment outcome were found to be smoker [ P = .04], Urinary tract infection (UTI) relative to other co-morbid condition [ P < .001], severe hypokalemia which increase risk of poor treatment outcome by around 4 times [ P = .02], and use of Metronidazole as a concurrent medication relative to other concurrent medication [ P = .03]. Conclusion: There was a high in-hospital mortality rate due to correctable causes. This mortality is unacceptable as it was majorly related to the poor practice of potassium supplementation and hypoglycemia due to insulin. Thus, clinicians and stakeholders should have to focus on modifiable factors (hypokalemia, UTI, and hypoglycemia) to reduce poor treatment outcome/in-hospital mortality.

A case of bortezomib-associated thrombotic microangiopathy in a multiple myeloma patient

Bortezomib is a first-generation proteasome inhibitor used in the treatment of multiple myeloma. We present a case of a 70-year-old woman with multiple myeloma, who presented thrombotic microangiopathy with multi-organ involvement thrombotic microangiopathy (ocular, cardiac, and renal) after bortezomib initiation. A kidney biopsy confirmed the diagnosis of thrombotic microangiopathy. A temporal relation between bortezomib exposure and thrombotic microangiopathy onset was seen in the absence of other concurrent medication or disease known to cause thrombotic microangiopathy, and thrombotic microangiopathy was only resolved after drug discontinuation. The exact pathophysiological mechanism remains unknown. To our knowledge, this is the second biopsy-proven published case of bortezomib-associated thrombotic microangiopathy. Since bortezomib is extensively used for treating patients with multiple myeloma, prescribing clinicians should maintain a high index of suspicion of this potentially fatal complication.

P046 Evaluating the safety of dose banding premedication (atropine, suxamethonium and fentanyl) for neonatal intubation (project NIK)

BackgroundThe process of prescribing and preparing premedication for intubation needs to be completed carefully to ensure the correct dose is prescribed and administered. Doses of atropine, suxamethonium and fentanyl were banded according to weight. The dose banding was implemented alongside pharmacy prepared neonatal intubation drug kits and a prescribing bundle on the neonatal electronic prescribing system, which automatically populates the doses according to the patient’s weight.AimTo evaluate the safety of dose banding neonatal premedication for intubation.MethodsA tool was developed to collect data including the patient’s weight, gestation, if dose banding had been used and whether any adverse effects were experienced with emphasis on hypotension, bradycardia, chest wall rigidity and prolonged paralysis. Data was collected from January 2018 to July 2018.ResultsOutcomes from 89 intubations using dose banding were reviewed. The corrected gestation of patients (n = 63) were 24+3 to 42+1 and the weight from 500 g to 4 kg. In 97.75% all three pre-medication drugs were given, the 2 cases that did not were due to rapid desaturations and the decision was made to intubate before all the medicines had been administered. All cases used the correct dose-banding for the medication. In all cases the fentanyl was administered over at least 1 minute with 7.87% receiving the fentanyl over more than 2 minutes. 95.5% of patients were normotensive within 30 minutes of intubation. Hypotension was observed in 2 cases >90 minutes post intubation. In two patients, a low mean blood pressure (BP) was observed prior to the decision to intubate and the premedication did not cause a further decrease in BP. No patients experienced bradycardia, chest wall rigidity or prolonged paralysis.ConclusionThis work has illustrated that dose-banding of intubation premedication is safe in this cohort of neonates and allows for successful intubation, whether the patient is 24 weeks or 42 weeks corrected gestational age. Chest wall rigidity may occur if fentanyl is administered too quickly. All patients received fentanyl over at least 1 minute, with the majority receiving over 1–2 minutes. The fentanyl dose is a very small volume, to ensure the dose was administered slowly, a flush was used to ensure that any remaining in the cannula was not bolused to the patient. Hypotension was seen in 2 patients >90 minutes after intubation which is unlikely to have been related to the use of neonatal intubation drugs. However this highlighted that not all patients are having BP monitoring 30 minutes post-intubation. An outcome has been to emphasise the need for this monitoring. Bradycardia and prolonged paralysis, two potentially prominent adverse effects, were not seen indicating that the atropine and suxamethonium doses were appropriate. A limitation of this study was that patients concurrent medication was not recorded. Data will continue to be collected to assess safety as this data set did not include babies in the <500 g banding. The next step will be to compare outcomes with patients that were intubated prior to the implementation of dose banding.

Effect of Comedications and Endotoxins on Mesenchymal Stem Cell Secretomes, Migratory and Immunomodulatory Capacity

Mesenchymal stem cells (MSCs) are becoming an increasingly popular therapeutic option among patients with a broad range of ailments to modulate immunity and induce regeneration. The majority of patients receiving these MSC therapies are on concurrent medication or have ongoing infection. In the present study, we examined the effect of immunosuppressive drugs and lipopolysaccharides (LPS)/endotoxins on the secretory profile, migration towards site of injury, and suppression of lymphocyte proliferation of bone marrow-derived MSCs (BMSCs). Generally, LPS coculture augmented the secretory capacity of BMSCs while exposure to immunosuppressive drugs resulted primarily in no change or attenuated secretion, with some cases of increased secretion, dependent on the cytokine assayed. Among the immunosuppressants evaluated, Hydrocortisone had the most widespread inhibitory effect, while LPS from E. coli O111:B4 had the most potent stimulatory effect. In addition, we also showed that Hydrocortisone or LPS from E. coli O111:B4 affected the migratory and immunosuppressive capacity of BMSCs. Following simulation with Hydrocortisone, BMSC migration was attenuated, and immunosuppressive capacity against T cell proliferation was enhanced, however, the opposite effects were seen with LPS from E. coli O111:B4. Our data suggests that the clinical outcomes of MSC-based therapy are affected by the use of immunosuppressive medication or the presence of endotoxemia in patients.

Impact of concurrent medications on outcomes with PD1/PD-L1 inhibitors for metastatic urothelial carcinoma.

435 Background: The impact of concurrent medications (meds) on outcomes with PD1/PD-L1 inhibitors in metastatic urothelial carcinoma (mUC) is unclear. We investigated whether candidate concurrent meds (NSAIDS [N], metformin [M], antibiotics [A], statins [S] and corticosteroids [C]) have an association with outcomes in mUC patients (pts) receiving a PD1/PD-L1 inhibitor. We hypothesized that A and C compromise outcomes, while N, M and S improve outcomes. Methods: Data from mUC pts who received PD1/PD-L1 inhibitors at the Dana-Farber Cancer Institute (DFCI) was obtained. The concurrent medication was required to be administered within 1 month before starting to anytime during PD1/PD-L1 inhibitor therapy. A Cox regression analysis was done to study the association of variables with response and survival. Results: Data was available for 101 pts with mUC who received atezolizumab [n = 52], pembrolizumab [n = 39], nivolumab [n = 9] and durvalumab [n = 1]. Prior platinum had been administered in 74 pts (73.2%), 25 were chemonaive (24.8%) and prior therapy status was unknown in 2 pts (2%). The concurrent meds were N (n = 30), M (n = 7), A (n = 26), S (n = 33) and C (n = 12). The median survival was 57.9 weeks. Response was seen in 26 pts [25.7%]. A was associated with a lower probability of response (11.5%) than those not on A (30.7%), and worse survival (HR = 1.93, 95% CI 1.93 – 3.42, P = 0.024). Pts who received neither A nor C, one of them or both had a response rate (RR) of 30.6%, 20% and 0%, and median survival of 65.3, 53.1 and 14.9 weeks, respectively (HR = 3.02, 95% CI = 1.34-6.83, p = 0.027). Pts who did not receive N, M and S (n = 52) exhibited a median OS of 39.6 weeks, while those who received ≥1 of these meds (n = 49) exhibited a median survival of 160.3 weeks (p = NS). The study is limited by the retrospective design and modest sample size. Conclusions: In this hypothesis-generating study, concurrent antibiotics or corticosteroids compromised outcomes in mUC pts receiving a PD1/PD-L1 inhibitor and receiving both further compromised outcomes. The numerically higher survival with concurrent N, M or S did not attain statistical significance, but requires further study in larger datasets.

Statins reduce the progression of non-advanced adenomas to colorectal cancer: a postcolonoscopy study in 187 897 patients

Background and aimsPostcolonoscopy colorectal cancer (PCCRC) accounts for up to 9% of all CRCs. Statins have been shown to be associated with a lower CRC risk. We aimed to investigate whether PCCRC risk was also lower among statin users.MethodsThis is a retrospective cohort study using a territory-wide electronic healthcare database in Hong Kong including patients aged 40 years or above who had undergone colonoscopies between 2005 and 2013. Exclusion criteria included prior colorectal cancer (CRC), inflammatory bowel disease, prior colectomy and CRC detected within 6 months of index colonoscopy. We defined statin use as at least 90-day use before index colonoscopy. Medication use was traced up to 5 years before index colonoscopy. PCCRC-3y was defined as cancer diagnosed between 6 and 36 months after index colonoscopy. Sites of CRC were categorised as proximal (proximal to splenic flexure) and distal cancer. The subdistribution HR (SHR) of PCCRC-3y with statin use was derived by propensity score matching based on covariates (including patient factors, concurrent medication use and endoscopy centre’s performance).ResultsOf 187 897 eligible subjects, 854 (0.45%) were diagnosed with PCCRC-3y. Statin use was associated with a lower PCCRC-3y risk (SHR: 0.72; 95% CI 0.55 to 0.95; p=0.018). Subgroup analysis shows that SHRs were 0.50 (95% CI 0.28 to 0.91; p=0.022) for proximal and 0.80 (95% CI 0.59 to 1.09; p=0.160) for distal cancer. Older (>60 years) patients, women and those without diabetes mellitus or polyps appeared to benefit more from statins.ConclusionsStatins were associated with a lower PCCRC risk, particularly for proximal cancer.