Nishkantha Arulkumaran

Nishkantha Arulkumaran
University College London | UCL · Centre for Intensive Care Medicine

About

110
Publications
18,116
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
2,628
Citations

Publications

Publications (110)
Article
Introduction Macrolide antibiotics have immunomodulatory properties which may be beneficial in viral infections. However, the precise effects of macrolides on T cell responses to COVID, differences between different macrolides, and synergistic effects with other antibiotics have not been explored. Methods We investigated the effect of antibiotics...
Article
Full-text available
Background: The COVID-19 pandemic increased the use of broad-spectrum antibiotics due to diagnostic uncertainty, particularly in critical care. Multiprofessional communication became more difficult, weakening stewardship activities. Aim: To determine changes in bacterial co-/secondary infections and antibiotics used in COVID-19 patients in criti...
Article
Full-text available
Background Bactericidal antibiotics are generally assumed to be superior to bacteriostatic antibiotics as first-line treatment for pneumonia. Objectives We performed a systematic review, meta-analysis, and trial sequential analysis (TSA) of randomized controlled trials of bactericidal versus bacteriostatic antibiotics to ascertain clinical outcome...
Article
Full-text available
PurposeThe integration of palliative care into intensive care units (ICUs) is advocated to mitigate physical and psychological burdens for patients and their families, and to improve end-of-life care. The most efficacious palliative care interventions, the optimal model of their delivery and the most appropriate outcome measures in ICU are not clea...
Article
Objectives Recent studies have demonstrated mortality benefits from corticosteroid use in COVID-19 patients requiring respiratory support. However, clinical practice may warrant the use of corticosteroids outside the context of a clinical trial. Such data are rarely, if ever, reported. We explored the use of corticosteroids for adult respiratory di...
Article
Full-text available
Objectives: Multiple mechanisms have been proposed to explain disease severity in coronavirus disease 2019. Therapeutic approaches need to be underpinned by sound biological rationale. We evaluated whether serum levels of a range of proposed coronavirus disease 2019 therapeutic targets discriminated between patients with mild or severe disease. D...
Article
Background: Our objective was to the describe indications, management, complications and outcomes of renal replacement therapy (RRT) in COVID-19 critically ill patients. To contextualise these findings, comparisons were made against 36 non-COVID-19 consecutive patients requiring RRT on ICU. Methods: We conducted a retrospective single centre obs...
Article
Full-text available
Background SARS-CoV-2-specific antibodies, particularly those preventing interaction between the viral spike receptor-binding domain and the host angiotensin-converting enzyme 2 receptor, may prevent viral entry into host cells and disease progression. Objective We performed a systematic review, meta-analysis, trials sequential analysis (TSA) and...
Article
Background Excess mitochondrial reactive oxygen species (mROS) in sepsis is associated with organ failure, in part by generating inflammation through the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome. We determined the impact of a mitochondrial-targeted antioxidant (MitoTEMPO) on mitochondrial dysfunction in renal proximal t...
Article
Purpose: Interleukin-6 (IL-6) levels discriminate between patients with mild and severe COVID-19, making IL-6 inhibition an attractive therapeutic strategy. We conducted a systematic review, meta-analysis, trial sequential analysis (TSA), and meta-regression of randomized-controlled trials to ascertain the benefit of IL-6 blockade with tocilizumab...
Article
Patients with COVID-19 ARDS have distinct physiological and immunological phenotypes compared to patients with non-COVID ARDS. Patients with COVID-19 ARDS (n = 32) had a significant improvement in PaO2: FiO2 ratio (p = 0.046) following low-dose steroid treatment, unlike patients with non-COVID ARDS (n = 16) (p = 0.529). Patients with COVID-19 ARDS...
Article
Full-text available
Background Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneo...
Article
Full-text available
Metabolically active gasotransmitters (nitric oxide, carbon monoxide and hydrogen sulfide) are important signalling molecules that show therapeutic utility in oxidative pathologies. The reduced form of selenium, hydrogen selenide (HSe-/H2Se), shares some characteristics with these molecules. The simple selenide salt, sodium hydroselenide (NaHSe) sh...
Article
Introduction: Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. We undertook a meta-analysis of randomized controlled trials (RCTs) to determine the mortality benefit of non-specialist therapeutic interventions for ARDS available to general critical care units. Evidence acquisition: A systematic s...
Article
Full-text available
An amendment to this paper has been published and can be accessed via the original article.
Article
DNA nanotechnology produces precision nanostructures of defined chemistry. Expanding their use in biomedicine requires designed biomolecular interaction and function. Of topical interest are DNA nanostructures that function as vaccines with potential advantages over nonstructured nucleic acids in terms of serum stability and selective interaction w...
Article
It remains unclear if intubation and ventilation earlier in the disease course confers a survival advantage in acute respiratory distress syndrome. Our objective was to determine whether patients with COVID-19 who died following mechanical ventilation were more advanced in their disease compared to survivors. Forty-seven patients admitted directly...
Article
Full-text available
Severe COVID‐19 disease is a hyperinflammatory, pro‐thrombotic state. We undertook plasma exchange (PEX) to determine its effects on organ function and thrombo‐inflammatory markers. Seven critically ill adults with severe COVID‐19 respiratory failure (PaO2:FiO2 ratio < 200 mm Hg) requiring invasive or noninvasive ventilatory support and elevated th...
Article
Introduction Severe COVID-19 disease is associated with a hyperinflammatory, pro-thrombotic state and a high mortality. A thrombotic phenotype rather than a coagulopathy is suggested and we undertook plasma exchange to determine its effects on organ function and thrombo-inflammatory markers. Methods Plasma exchange was carried out in seven critical...
Article
Objective: The objective of this study was to conduct a meta-analysis and trial sequential analysis (TSA) of published randomized controlled trials (RCTs) to determine whether mortality benefit exists for extracorporeal blood purification techniques in sepsis. Data sources: A systematic search on MEDLINE, Embase, and the Cochrane Central Registe...
Preprint
Full-text available
Background: To compare differences in indications, management, complications and outcomes of renal replacement therapy (RRT) in COVID-19 patients compared to non-COVID critically ill patients. Methods: We conducted a retrospective observational single centre cohort study in UK. Patients with COVID-19 requiring RRT, compared to consecutive, non-COVI...
Article
Full-text available
Objective: This study aimed to determine the relationship between early postoperative nonsteroidal anti-inflammatory drug (NSAID) administration and postoperative acute kidney injury (AKI) and anastomotic leak. Summary background data: NSAIDs have analgesic, opioid-sparing, and anti-inflammatory effects. However, their postoperative use is limited...
Article
Objective: To investigate methods of antibiotic duration minimization and their effect on mortality and infectious complications in critically ill patients. Data sources: A systematic search of PubMed, Embase (via Ovid), clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials (via Wiley) (CENTRAL, Issue 2, 2015). Study select...
Article
The belief that, for the individual patient, the benefit of prompt and continued use of antimicrobials outweighs any potential harm is a significant barrier to improved stewardship of these vital agents. Antimicrobial stewardship may be perceived as utilitarian rationing, seeking to preserve the availability of effective antimicrobials by limiting...
Article
Full-text available
Background: Trainee research collaboratives (TRCs) have pioneered high quality, prospective 'snap-shot' surgical cohort studies in the UK. Outcomes After Kidney injury in Surgery (OAKS) was the first TRC cohort study to attempt to collect one-year follow-up data. The aims of this study were to evaluate one-year follow-up and data completion rates,...
Article
Full-text available
Conducting clinical trials in critical care is integral to improving patient care. Unique practical and ethical considerations exist in this patient population that make patient recruitment challenging, including narrow recruitment timeframes and obtaining patient consent often in time-critical situations. Units currently vary significantly in thei...
Article
We were surprised to read the letter by Berti and colleagues ¹ , commenting on our recent article on the incidence of arterial and venous thrombosis in antineutrophil cytoplasmic antibody–associated vasculitis (AAV) ² . They make the unjustified comment that “the incidence estimates for [arterial (ATE) and venous thrombosis events (VTE)] may be inf...
Article
Full-text available
Background: Even though data suggest that palliative care (PC) improves patient quality of life, caregiver burden, cost, and intensive care unit (ICU) length of stay, integration of PC in the ICU is far from being universally accepted. Poor understanding of what PC provides is one of the barriers to the widespread implementation of their services...
Article
Full-text available
We thank Dr. Rothschild for his interest ¹ in our article ² on the incidence of arterial and venous thrombosis in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). He raises the interesting issue of susceptibility to both arterial and venous thrombotic events, which is also characteristic of antiphospholipid syndrome.
Article
Full-text available
Background: Patients who require acute initiation of dialysis have higher mortality rates when compared with patients with planned starts. Our primary objective was to explore the reasons and risk factors for acute initiation of renal replacement therapy (RRT) among patients with end-stage kidney disease (ESKD). Our secondary objective was to dete...
Article
Objective: To determine the incidence of arterial thrombotic events (ATE) and venous thromboembolism (VTE) in antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods: This is a retrospective cohort study presenting the incidence of ATE (coronary events or ischemic stroke) and VTE [pulmonary embolism (PE) or deep venous thrombosi...
Article
The peri‐operative use of angiotensin‐converting enzyme inhibitors or angiotensin‐2 receptor blockers is thought to be associated with an increased risk of postoperative acute kidney injury. To reduce this risk, these agents are commonly withheld during the peri‐operative period. This study aimed to investigate if withholding angiotensin‐converting...
Article
Objective: To summarize the results of randomized controlled trials on the use of vasopressin as a vasopressor agent in cardiac surgery. Design: Meta-analysis. Participants: Six-hundred-twenty-five adult patients undergoing elective or emergency cardiac surgery. Interventions: Arginine vasopressin infusion (n = 313) or control/standard thera...
Article
Full-text available
Sepsis is a major clinical problem associated with significant organ dysfunction and high mortality. The ATP-sensitive P2X7 receptor activates the NLRP3 inflammasome and is a key component of the innate immune system. We used a fluid-resuscitated rat model of fecal peritonitis and acute kidney injury (AKI) to investigate the contribution of this pu...
Article
Videolaryngoscopy (VL) may improve the success of orotracheal intubation compared with direct laryngoscopy (DL). We performed a systematic search of PubMed, Embase, and CENTRAL databases for studies comparing VL and DL for emergency orotracheal intubations outside the operating room. The primary outcome was rate of first-pass intubation, with subgr...
Article
Full-text available
Introduction: We evaluated intensive care medicine trainees' practice of emergency intubations in the United Kingdom. Methods: Retrospective analysis of 881 in-hospital emergency intubations over a three-year period using an online trainee logbook. Results: Emergency intubations out-of-hours were less frequent than in-hours, both on weekdays a...
Article
Full-text available
Objective: To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury. Design: Prospective observational animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Intervention: Using a fluid-resuscitated sublethal rat model o...
Chapter
Importance A number of common clinical conditions are associated with severe inflammation, including sepsis and major surgery. The excessive inflammatory response results in shock states and ‘multiorgan dysfunction syndrome’ (MODS), which is often the final common pathway before death. Objective To understand the mechanisms that underlie MODS and...
Article
Full-text available
Background The fluid challenge is considered the gold standard for diagnosis of fluid responsiveness. The objective of this study was to describe the fluid challenge techniques reported in fluid responsiveness studies and to assess the difference in the proportion of ‘responders,’ (PR) depending on the type of fluid, volume, duration of infusion an...
Article
Full-text available
Objectives: Organizational factors are associated with outcome of critically ill patients and may vary by time of day and day of week. We aimed to identify the association between out-of-hours admission to critical care and mortality. Data sources: MEDLINE (via Ovid) and EMBASE (via Ovid). Study selection: We performed a systematic search of t...
Article
Full-text available
Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such ‘double-positive’ cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients with ANCA-associated vasculitis...
Article
Full-text available
Objectives: To characterize the temporal pattern of a panel of blood and urinary biomarkers in an animal model of fecal peritonitis and recovery. Design: Prospective observational animal study. Setting: University research laboratory. Subjects: Male Wistar rats. Interventions: A fluid-resuscitated, long-term (3 d) rat model of sepsis (feca...
Article
Background: We aimed to identify any association between day and time of admission to critical care and acute hospital outcome. Methods: We conducted a cohort study using prospectively collected data from the national clinical audit of adult critical care. We included 195 428 unplanned admissions from 212 adult general critical care units in Eng...
Conference Paper
Acute kidney injury (AKI) is a common clinical problem within the intensive care unit. Sepsis is implicated in half the cases of AKI; in those patients requiring acute renal replacement therapy there is an associated mortality of 50%. However, other than maintenance of an adequate circulation, no specific therapy exists for septic AKI. This is in l...
Article
Full-text available
Background: Clinical trials in critical care are often resource-intense, with many unique challenges. Barriers to effective recruitment and implementation of study intervention have not been explored in a UK context. Aim: To identify facilitating factors and barriers to enrolling patients into critical care clinical trials within the UK from cli...
Article
Mitochondria are an essential part of the cellular infrastructure, being the primary site for high-energy adenosine triphosphate production through oxidative phosphorylation. Clearly, in severe systemic inflammatory states, like sepsis, cellular metabolism is usually altered, and end organ dysfunction is not only common, but also predictive of long...
Article
Full-text available
Introduction: Acute kidney injury (AKI) is associated with increased morbidity and mortality following cardiac surgery. Data focusing on the patterns of AKI following major gastrointestinal surgery could inform quality improvement projects and clinical trials, but there is a lack of reliable evidence. This multicentre study aims to determine the i...
Article
The Intensive Care Foundation, in partnership with the James Lind Alliance, has supported a national project to identify and prioritise unanswered questions about adult intensive care that are important to people who have been critically ill, their families, and the health professionals who care for them. We conducted a secondary analysis to explor...
Article
Full-text available
Objective: Severe trauma can be associated with significant hemorrhagic shock and impaired organ perfusion. We hypothesized that goal-directed therapy would confer morbidity and mortality benefits in major trauma. Methods: The MedLine, Embase and Cochrane Controlled Clinical Trials Register databases were systematically searched for randomized,...
Article
This James Lind Alliance (JLA) Priority Setting Partnership aimed to identify and prioritise unanswered questions about adult intensive care that are important to people who have been critically ill, their families, and the health professionals who care for them. Consensus techniques (modified Delphi and Nominal Group) were used to generate suggest...