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Press Releases

Take a look at a selection of our recent media coverage:

Intravenous vitamin C associated with increased mortality risk in sepsis patients

24th June 2022

Intravenous vitamin C given to sepsis patients receiving vasopressor therapy increased the risk of death and persistent organ dysfunction

The use of intravenous vitamin C for intensive care patients with sepsis who were also in receipt of vasopressor therapy, increased the risk of both death and persistent organ dysfunction according to the findings of LOVIT, a randomised, placebo-controlled trial.

Sepsis represents the body’s inflammatory response to infection and has been found to be the cause of one in every two to three hospital deaths, most of whom had sepsis upon admission to hospital. Moreover, sepsis represents a major cause of death, with an estimated 48·9 million global incident cases and 11·0 million sepsis-related deaths in 2017. Intravenous vitamin C may be an important adjunctive therapy for critically ill patients. In fact, evidence suggests that critically ill patients have low vitamin C concentrations and that those with septic shock have significantly depleted vitamin C levels probably due to the increased metabolism from the enhanced inflammatory response in these patients. In a 2017 retrospective study, researchers observed that the use of intravenous vitamin C in sepsis patients, together with corticosteroids and thiamine, was effective in preventing progressive organ dysfunction and in reducing the mortality of patients with severe sepsis and septic shock. However, subsequent studies were less consistent, with one network meta-analysis concluding that metabolic resuscitation with vitamin C, glucocorticoids, vitamin B1, or combinations of these drugs was not significantly associated with a decrease in longer-term mortality. In contrast, another meta-analysis concluded that intravenous vitamin C administration appeared to be safe and may be associated with a trend toward reduction in overall mortality in critically ill patients. Nevertheless, in another study of167 patients with sepsis and acute respiratory distress syndrome, a 96-hour infusion of vitamin C compared did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury.

Given the potentially conflicting results to date on the value of vitamin C, for the present study, researchers undertook a randomised, placebo-controlled trial, Lessening Organ Dysfunction with Vitamin C (LOVIT). The trial was designed to test whether intravenous vitamin C would reduce both the risk of death or persistent organ dysfunction in adults with sepsis and who were receiving vasopressor therapy within an intensive care unit (ICU). The team recruited adult patients who had been within an ICU for no longer than 24 hours, with a proven or suspected infection as the main diagnosis and who were receiving a vasopressor. Participants were randomised 1:1 to receive intravenous vitamin C as a bolus dose of 50 mg/kg, administered over 30 to 60 minutes every 6 hours for a total of 96 hours. The control group received a matching infusion containing either 5% dextrose or normal saline. The primary outcome of the trial was a composite of death or persistent organ dysfunction, whereas one of the secondary outcomes was 28-day mortality.

Intravenous vitamin C and death or persistent organ dysfunction

A total of 863 patients with a mean age of 65.1 years (37.6% female) were randomised to either intravenous vitamin C or matching placebo. The median stay within the ICU was 6 days and with an overall hospital stay of 16 days.

The primary outcome occurred in 44.5% of those in the vitamin C group and 38.5% of placebo patients and this difference was significant (risk ratio, RR = 1.21, 95% CI 1.04 – 1.40, p = 0.01).

For the secondary outcome of 28-day mortality, death occurred in 35.4% of those using vitamin C and 31.6% of those receiving placebo (RR = 1.17, 95% CI 0.98 – 1.40). Similarly, the proportion of patients with persistent organ dysfunction was present in 9.1% of those given vitamin C and 6.9% of those taking placebo (RR = 1.30, 95% CI 0.83 – 2.05).

The authors concluded that in adults with sepsis who were receiving vasopressor therapy, use of intravenous vitamin C led to a higher risk of death or persistent organ dysfunction compared to placebo.

Citation
Lamontagne F et al. Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit N Eng J Med 2022

Early intravenous fluid use for sepsis patients in ED improved by range of interventions

4th February 2022

Early intravenous fluid use in emergency department patients with sepsis increased after implementing performance interventions

Early intravenous fluid use in sepsis patients seen at emergency departments has been found to increase after the introduction of several improvement interventions. This was the conclusion of a study by a team from Western Sydney University, School of Nursing and Midwifery, Australia.

Sepsis is a syndrome of physiologic, pathologic and biochemical abnormalities which is induced by infection. Although the global burden is difficult to ascertain with a high degree of certainty, the World Health Organization reports that in 2017, there were an estimated 48.9 million cases and as many as 11 million sepsis-related deaths globally.

Early intravenous fluid resuscitation is crucial for stabilisation of sepsis-induced tissue hypo-perfusion or septic shock and has been recommended by the ‘Surviving Sepsis Campaign’ guideline in 2017. In the latest update, it is recommended that crystalloid fluid should be given within the first 3 hours of resuscitation.

The Australian team wondered to what extent any interventions to improve early intravenous fluid administration might improve compliance with the sepsis guidelines and set out to find an examine the value of any such interventions. The team undertook a literature search for studies in adults presenting at an emergency department with sepsis and included those trials where the purpose of the intervention or strategy was to influence early intravenous fluid administration, for example, through educational programs, sepsis alerts or inclusion in sepsis protocols.

Findings

A total of 31 studies were included in the analysis. In 15 of these studies with a total of 1538 patients assigned to the intervention arm, the summary estimate indicated a 47% improvement in the rate of compliance with early intravenous fluid use (relative risk, RR = 1.47, 95% CI 1.25 – 1.74, p < 0.01).

The mean difference in time to initiation of early fluids was – 24.11 minutes, i.e., an average reduction of 24 minutes in the time to fluid resuscitation between intervention and control groups. Similarly, patients received an average additional 575 ml of fluids within the protocol recommended time as a result of the intervention.

In discussing their findings, the authors reported how early intravenous fluid administration compliance increased by an average 47% and more importantly, this improvement was seen in a variety of emergency departments across the world. The authors described how there were a range of interventions employed which ranged from educational to process change measures such as a multidisciplinary sepsis program.

They concluded that performance improvement initiatives appeared to significantly improve compliance with early intravenous fluid administration and called for future studies to examine the subjective factors influencing the use of an early fluid bolus.

Citation

Kabil G et al. Early fluid bolus in adults with sepsis in the emergency department: a systematic review, meta-analysis and narrative synthesis BMC Emerg Med 2022

Pharmacist sepsis notification system improves patient outcomes

13th September 2021

A sepsis notification system contained within electronic health records monitored by pharmacists significantly improved patient outcomes.

Sepsis is a life-threatening organ dysfunction response to infection which, according to the World Health Organization, in 2017, affected 48.9 million people and caused 11 million sepsis-related deaths. The early administration of broad-spectrum antibiotics is associated with a reduced progression to severe sepsis and septic shock and a lower mortality. These findings have prompted the development of several automated rule-based sepsis notification systems which have been combined with alerting systems. In a review of studies, it was concluded that digital sepsis alerting systems, reduce both hospital and intensive care unit stays for patients with sepsis. The incorporation of sepsis notification systems within electronic health records (EHRs), providing a real-time alert, could therefore lead to improvements in patient outcomes although recent trial concluded that this was not the case.

Whether sepsis notification systems incorporated into EHRs and monitored by an emergency department pharmacist could improve patient outcomes was the subject of a study by a team from the Division of Pulmonary and Critical Care Medicine, MetroHealth Medical Centre, Cleveland, Ohio, US.

The team incorporated a sepsis alert within with the EHR and randomised patients admitted to hospital with suspected sepsis to either standard care or augmented care (intervention group) in which the sepsis early-warning system (EWS) was visible and monitored by an emergency department pharmacist. Once the sepsis EWS score crossed over the established threshold, an alert occurred, triggering a flag that was displayed on the patient emergency department tracking tool and a message to the EHR system which was monitored by an emergency department pharmacist. Once an alert was raised, the pharmacist ordered appropriate blood tests, antibiotics and fluid boluses for the patient. The primary outcome measure was time to antibiotics from arrival and the primary clinical outcome score was a composite of days alive and out of hospital, 28 days after arrival.

Findings
A total of 598 patients were included over a 5-month period and randomised to standard care (313) or intervention. The median age of participants ranged from 62.3 (standard care) to 61.5 (intervention group) years with the proportion of females ranging from 46% to 51.2%, standard care and intervention group respectively. Among those assigned to the intervention arm, the time to antibiotic administration from emergency department arrival was 2.3 hours compared with 3 hours in the standard care group (p = 0.039). In addition, the clinical primary outcome score was also higher for the intervention, reflecting better outcomes (median 24.1 vs 22.5 days, p = 0.011). However, the length of stay between groups was not significantly different (p = 0.124) and neither was hospital mortality (p = 0.086).

In their discussion, the authors noted how their results showed only a slightly modest improvement from the intervention. The study was designed as a quality improvement initiative to compare whether visibility of the sepsis notification systems by both clinicians and pharmacists improved outcomes. They concluded that further studies are needed to determine if their approach is generalisable to other healthcare settings.

Citation
Tarabichi Y et al. Improving Timeliness of Antibiotic Administration Using a Provider and Pharmacist Facing Sepsis Early Warning System in the Emergency Department Setting: A randomised Controlled Quality Improvement Initiative. Crit Care Med 2021.

Machine learning model predictive of mortality in sepsis

26th July 2021

In patients with sepsis, the use of a machine learning algorithm identified six variables that were predictive of 7- and 30-day mortality.

Sepsis can be defined as is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Furthermore, sepsis is responsible for around 11 million deaths each year, which amounts to approximately 20% of all global deaths. Thus, it is crucial that clinicians have a comprehensive understanding of all the relevant clinical factors that can help with the early identification of those patients for whom a poor outcome is likely. This is particularly important since early use of crystalloid therapy reduces mortality, as does prompt administration of antibiotics. Though several scoring systems for sepsis are available, these are based on the assessment of vital signs but which can sometimes be normal upon admission to an emergency department. While machine learning has been shown to have some level of predictive power for mortality, none of the variables currently used in these models are reflective of the symptoms at first presentation. This led a team from the Department of Medical Sciences, Orebro University, Sweden, to use machine learning in an attempt to identify the variables which were predictive of 7- and 30-day mortality in sepsis patients, based on the clinical presentation at an emergency department. They employed a retrospective design and included patients 18 years and older, admitted to hospital with suspected sepsis. The team input previously identified variables, e.g., abnormal temperature, acute altered mental status, etc into the machine learning algorithm. The sensitivity and specificity of the predictive models generated by the machine learning model, were calculated from the area under the receiver operating curve (AUC).

Findings
A total of 445 patients with sepsis and a median age of 73 years (52.6% male) were included in the retrospective analysis. Overall, 234 (49.7%) had severe sepsis and 63 patients died within 7-days of admission and 98 within 30 days. The accuracy of the 7-day predictive model was maximal after the inclusion of only six variables; fever, abnormal verbal response, low oxygen saturation, arrival by emergency services, abnormal behaviour/level of consciousness and chills. Using these variables, the AUC sensitivity was 0.84 (95 CI 0.78–0.89) and the specificity 0.67 (95% CI 0.64 –0.70). For the prediction of 30-day mortality, again, only 6 variables were significant; abnormal verbal response, fever, chills, arrival by emergency services, low oxygen saturation and breathing difficulties. This model gave a sensitivity of 0.87 (95% CI 0.81–0.93) and a specificity of 0.64 (95% CI 0.61–0.67).

In discussing their findings, the authors highlighted how their results revealed the importance of the using a clinical symptom complex that was representative of what an emergency department clinician would be likely to encounter in practice. They also suggested that the 7-day model might be of more use in practice since it would be of assistance to emergency care staff for the likely short-term outcome for patients. They concluded that given how the clinical presentation of sepsis can often be non-specific, the use of a machine learning algorithm, based on symptoms and observations, would be most helpful to staff and that future work should focus on validating the method in other cohorts.

Citation
Karlsson A et al. Predicting mortality among septic patients presenting to the emergency department– a cross sectional analysis using machine learning. BMC Emerg Med 2021