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Take a look at a selection of our recent media coverage:
16th January 2023
A diagnostic aid based on polymerase chain reactions (PCR), that uses a 52-pathogen custom array card, has been found to provide both rapid (compared to blood culture) and reliable information on respiratory infections in critically ill, mechanically ventilated children, according to a study by UK researchers.
Respiratory tract infections are responsible for a large number of admissions to paediatric intensive care units. Moreover, an intensive care unit is unique environment and for which clinicians often make decisions to use antibiotics with some degree of diagnostic uncertainty. This was clearly illustrated in one study of paediatric intensive care unit children, where despite most critically children receiving antimicrobial therapy, infection was often not microbiologically confirmed. While in many cases, respiratory infections are viral in nature, it is necessary to utilise methods such as quantitative PCR, as a diagnostic aid to identify the presenting pathogens. In fact, a recent study in adults found that multiplex bacterial PCR examination of bronchoalveolar lavage, reduced the duration of inappropriate antibiotic therapy of patients admitted to hospital with pneumonia and who were at risk of Gram-negative infection. In the current study, researchers made use of the TaqMan Array Card (TAC) as a diagnostic aid which is a microfluidic quantitative PCR system comprising of 384 wells containing pre-aliquoted customised primer and probe combinations. The aid has been previously shown to be of value in supporting ventilator-associated pneumonia (VAP) diagnosis in adults. Nevertheless, it has not been examined in critically ill children and therefore, the aim of the present study was to assess the utility of TAC to identify bacterial and fungal respiratory pathogens in critically ill children with suspected community acquired pneumonia or VAP. The study recruited children ≤ 18 years of age and if they were mechanically ventilated and had commenced or were commencing antimicrobial therapy for a lower respiratory tract infection. The researchers determined the sensitivity and specificity of TAC to detect bacterial and fungal pathogens causing lower respiratory tract infections and the time to a result provided by TAC compared to standard microbiology cultures. Secondary objectives included a description of the micro-organisms detected by TAC but not by microbiology culture as well as the impact of TAC on antimicrobial decision-making.
Diagnostic aid and outcomes
A total of 100 children with a median age of 1.2 years (58% male) were included in the study and of whom, 80 had suspected community acquired pneumonia and the remainder, hospital acquired pneumonia.
Bacteria were detected more frequently on TAC compared to microbiology cultures (57% vs 18%, p < 0.001)) and In addition, TAC also identified more fungi (17% vs 2%, p < 0.001).
For the detection of bacterial and fungal species, TAC had a sensitivity of 89.5% (95% CI 66.9 – 98.7) and a specificity of 97.9% (95% CI 97.2 – 98.5). The median time to obtain a result for the diagnostic aid was 25.8 hours compared to 110.4 hours for microbiological cultures and overall, TAC was significantly quicker for both positive and negative results (p < 0.001).
Finally, consultants reported a change of prescription in 47% of cases based upon TAC results. Antimicrobial therapy duration was reduced or stopped in 26% of children, extended in16% and the spectrum of treatment was broadened in 17% of cases and reduced in 17%.
The authors concluded that as a diagnostic aid, TAC can be used to reliably detect pathogens quicker than routine culture in critically ill children with suspected lower respiratory tract infections and called for future studies to incorporate antimicrobial decision support and economic analysis.
Clark JA et al. The rapid detection of respiratory pathogens in critically ill children. Crit Care, 2023
11th November 2022
Using either a lower, intermediate or higher oxygen saturation target does not affect 28-day mortality or the number of mechanical ventilation-free days among critically ill patients according to the findings of the PILOT randomised trial by US researchers.
Invasive mechanical ventilation is an intervention that is frequently used in patients with acute respiratory failure, and which can be hypoxic or hypercapnic. Nevertheless, such patients are at a high risk of death with one study finding that nearly half (44%) of patients receiving mechanical ventilation for longer than 14 days died. The fraction of inspired oxygen is adjusted in mechanically ventilated patients to maintain arterial oxygen saturation although the oxygenation target which provides the best clinical outcomes for patients remains unclear. For example, too much oxygen (hyperoxemia) can result in acute lung injury, whereas hypoxia is associated with tissue damage and increased in-hospital mortality. Moreover, trial data on the optimal oxygen target are conflicting. For instance, using either a low-normal or high-normal showed no difference in organ dysfunction, whereas another study found that a conservative protocol for oxygen therapy versus conventional therapy resulted in lower intensive care mortality. In contrast, use of a higher target, i.e., more liberal oxygen therapy improved 28-day mortality compared to a conservative-oxygenation strategy.
For the present PILOT study, patients within an emergency and critical care department were randomised to a lower target for oxygen saturation (90%), an intermediate target (94%) or a higher target (98%). The primary outcome was the number of days alive and free of mechanical ventilation (ventilation-free days), defined from the day of ventilation through to day 28. The sole secondary outcome was death from any cause by day 28.
Oxygen saturation target and mortality
A total of 2541 patients with a median age of 53.3 years (45.4% female) were randomised to either the lower (808), intermediate (859) or higher oxygen target (874).
The median number of ventilation-free days ranged from 20 to 21 for the three groups and was not statistically different (p = 0.81). Similarly, there were no significant differences between the groups for in-hospital mortality at day 28. In addition, there were no differences in the incidence of adverse cardiac events e.g., arrhythmia or myocardial infarction.
The authors concluded that ventilation-free days did not differ depending on the oxygen saturation target.
Semler MW et al. Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation. N Eng J Med 2022
16th September 2022
Vitamin D administration to critical care patients leads to a significant reduction in mortality, the length of stay in critical care and the need for mechanical ventilation according to the findings of a systematic review and meta-analysis by European and Canadian researchers.
Except for rare circumstances such as the complete absence of UV radiation, the human body can synthesise vitamin D. Whilst the vitamin is known to play a role in the regulation of calcium and phosphate levels in circulation, the active metabolite of vitamin D, calcitriol, has been found in vitro to up-regulate different anti-inflammatory pathways. Furthermore, as dysregulated host immune responses to infection often occur, leading to sepsis, multiple organ failure, and death, vitamin D deficiency appears to be associated with an increased susceptibility of sepsis. In fact, a 2020 meta-analysis suggested that severe vitamin D deficiency may be independently associated with increased mortality in adult patients with sepsis. Nevertheless, based on the currently available evidence, it seems that correction of a deficiency, through high dose vitamin D administration to critically ill patients does not reduce hospital length of stay, hospital mortality, or 6-month mortality compared to placebo, unless patients had severe deficiency of the vitamin. Despite this, one small trial in 36 patients with COVID-19, did find that high dose (300,000 IU) vitamin D administration to intensive care patients, decreased the length of stay and duration of mechanical ventilation.
Given this uncertainty, for the present study, researchers undertook a systematic review and meta-analysis of clinical outcomes in critically ill patients given vitamin D. They focused on randomised trials that included adults treated within an intensive care unit and for whom vitamin D administration or its metabolite, was provided via either an enteral or parenteral route. Studies were also required to have a comparator group who received standard care and which reported on the outcomes of interest, i.e., mortality, length of intensive care unit (ICU) and hospital stay or the duration of mechanical ventilation. The primary outcome of interest was overall mortality, whereas secondary outcomes were hospital and ICU length of stay and the duration of mechanical ventilation.
Vitamin D administration and critical care outcomes
A total of 16 studies with 2449 patients were included in the analysis. Only 12 studies included vitamin D deficient patients (i.e., < 30 ng/mL) whereas the remaining 4 studies did not specify a threshold.
In terms of mortality, vitamin D administration was associated with a 22% reduced risk of death compared to placebo (risk ratio, RR = 0.78, 95% CI 0.62 – 0.97, p = 0.03). With respect to ICU length of stay, vitamin D supplementation lead to a mean difference in length of stay (compared to placebo) of 3.13 days (95% CI -5.36 to – 0.89, p = 0.006). Based on 7 studies, the length of hospital stay was no different to placebo. Finally, vitamin D administration was significantly associated with a reduction in the number days for which patients required mechanical ventilation (mean difference = -5.07 days, 95% CI -7.42 to -2.73, p < 0.0001). There was also an important effect of the route of administration, with parenteral having a more significant effect on mortality compared to the enteral route.
The authors concluded that vitamin D administration may be associated with a lower mortality among critically ill patients. However, they added that since several smaller and inconsistent studies with an inherent risk of bias were included, larger and more definitive trials were needed to support the findings regarding the type of supplementation and specific populations that achieve the greatest benefit.
Menger J et al. Administration of vitamin D and its metabolites in critically ill adult patients: an updated systematic review with meta-analysis of randomized controlled trials Crit Care 2022