Effect of Vitamin C Infusion on Organ Failure and Biomarkers of Inflammation and Vascular Injury in Patients With Sepsis and Severe Acute Respiratory Failure: The CITRIS-ALI Randomized Clinical Trial.

This article by Fowler et al was published in JAMA during October 2019 in volume 322 issue 13.
Importance:  Experimental data suggest that intravenous vitamin C may attenuate inflammation and vascular injury associated with sepsis and acute respiratory distress syndrome (ARDS).
Objective:  To determine the effect of intravenous vitamin C infusion on organ failure scores and biological markers of inflammation and vascular injury in patients with sepsis and ARDS.
Design, Setting, and Participants:  The CITRIS-ALI trial was a randomized, double-blind, placebo-controlled, multicenter trial conducted in 7 medical intensive care units in the United States, enrolling patients (N = 167) with sepsis and ARDS present for less than 24 hours. The study was conducted from September 2014 to November 2017, and final follow-up was January 2018.InterventionsPatients were randomly assigned to receive intravenous infusion of vitamin C (50 mg/kg in dextrose 5% in water, n = 84) or placebo (dextrose 5% in water only, n = 83) every 6 hours for 96 hours.
Main Outcomes and Measures:  The primary outcomes were change in organ failure as assessed by a modified Sequential Organ Failure Assessment score (range, 0-20, with higher scores indicating more dysfunction) from baseline to 96 hours, and plasma biomarkers of inflammation (C-reactive protein levels) and vascular injury (thrombomodulin levels) measured at 0, 48, 96, and 168 hours.
Results:  Among 167 randomized patients (mean [SD] age, 54.8 years [16.7]; 90 men [54%]), 103 (62%) completed the study to day 60. There were no significant differences between the vitamin C and placebo groups in the primary end points of change in mean modified Sequential Organ Failure Assessment score from baseline to 96 hours (from 9.8 to 6.8 in the vitamin C group [3 points] and from 10.3 to 6.8 in the placebo group [3.5 points]; difference, -0.10; 95% CI, -1.23 to 1.03; P = .86) or in C-reactive protein levels (54.1 vs 46.1 μg/mL; difference, 7.94 μg/mL; 95% CI, -8.2 to 24.11; P = .33) and thrombomodulin levels (14.5 vs 13.8 ng/mL; difference, 0.69 ng/mL; 95% CI, -2.8 to 4.2; P = .70) at 168 hours.
Conclusions and Relevance:  In this preliminary study of patients with sepsis and ARDS, a 96-hour infusion of vitamin C compared with placebo did not significantly improve organ dysfunction scores or alter markers of inflammation and vascular injury. Further research is needed to evaluate the potential role of vitamin C for other outcomes in sepsis and ARDS.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Outcomes of emergency laparotomy in patients on extracorporeal membrane oxygenation for severe respiratory failure: A retrospective, observational cohort study

This research by McCann and others was first issued on line during late June 2019 in the Journal of Critical Care.
Purpose:  There is a paucity of literature to support undertaking emergency laparotomy when indicated in patients supported on ECMO. Our study aims to identify the prevalence, outcomes and complications of this high risk surgery at a large ECMO centre.
Materials and methods:  A single centre, retrospective, observational cohort study of 355 patients admitted to a university teaching hospital Severe Respiratory Failure service between December 2011 and January 2017.
Results:  The prevalence of emergency laparotomy in patients on ECMO was 3.7%. These patients had significantly higher SOFA and APACHEII scores compared to similar patients not requiring laparotomy. There was no difference in the duration of ECMO or intensive care unit (ICU) stay post decannulation between the two groups. 31% of laparotomy patients survived to hospital discharge. Major haemorrhage was uncommon, however emergency change of ECMO oxygenator was commonly required.
Conclusion:  Survival to hospital discharge is possible following emergency laparotomy on ECMO, however the mortality is higher than for those patients not requiring laparotomy, this likely reflects the severity of underlying organ failure rather than the surgery itself. Our service’s collocation with a general surgical service has made this development in care possible. ECMO service planning should consider general surgical provision.
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High flow nasal therapy in immunocompromised patients with acute respiratory failure: A systematic review and meta-analysis

This research by Cortegiani and others was published in the Journal of Critical Care during December 2018.
Purpose:  The role of high-flow nasal therapy (HFNT) as compared to conventional oxygen therapy (COT) in immunocompromised patients admitted to intensive care unit (ICU) with acute respiratory failure (ARF) remains unclear. We conducted a systematic review and meta-analysis in order to address this issue.
Methods:  We searched PubMed, Medline and Embase until November 7th, 2018. Randomized controlled trials (RCTs), non-randomized prospective and retrospective evidence were selected. Observational studies were considered for sensitivity analysis. Primary outcome was mortality rate; intubation rate was a secondary outcome.
Results:  We included four studies in the primary analysis: one RCT, two RCT’s post-hoc analyses and one retrospective study. We found no significant difference in short-term mortality comparing HFNT vs. COT: 1) ICU: n = 872 patients, odds ratio (OR) = 0.80 [0.44,1.45], p = 0.46, I2 = 30%, p = 0.24; 2) 28-day: n = 996 patients, OR = 0.79 [0.45,1.38], p = 0.40, I2 = 52%, p = 0.12). Conversely, we found a reduction of intubation rate in the HFNT group (n = 1052 patients, OR = 0.74 [0.55,0.98], p = 0.03, I2 = 7%, p = 0.36). The inclusion of one observational study for sensitivity analysis did not grossly change results.
Conclusions:  We found no benefit of HFNT over COT on mortality in immunocompromised patients with ARF. However, HFNT was associated with a lower intubation rate warranting further research.
The full text of articles from issues older than sixty days is available via this link to an archive of issues of Journal of Critical Care.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Effect of Protocolized Weaning With Early Extubation to Non-invasive Ventilation vs Invasive Weaning on Time to Liberation From Mechanical Ventilation Among Patients With Respiratory Failure: The Breathe Randomized Clinical Trial

This article by Perkins and colleagues was published in JAMA during November 2018.
Importance:  In adults in whom weaning from invasive mechanical ventilation is difficult, non-invasive ventilation may facilitate early liberation, but there is uncertainty about its effectiveness in a general intensive care patient population.
Objective:  To investigate among patients with difficulty weaning the effects of protocolized weaning with early extubation to non-invasive ventilation on time to liberation from ventilation compared with protocolized invasive weaning.
Design,Setting, and Participants:  Randomized,allocation-concealed, open-label, multicenter clinical trial enrolling patients between March 2013 and October 2016 from 41 intensive care units in the UK National Health Service. Follow-up continued until April 2017. Adults who received invasive mechanical ventilation for more than 48 hours and in whom a spontaneous breathing trial failed were enrolled.
Interventions:  Patients were randomized to receive either protocolized weaning via early extubation to non-invasive ventilation (n = 182)or protocolized standard weaning (continued invasive ventilation until successful spontaneous breathing trial, followed by extubation) (n = 182).
Main Outcomes and Measures:  Primary outcome was time from randomization to successful liberation from all forms of mechanical ventilation among survivors, measured in days, with the minimal clinically important difference defined as 1 day. Secondary outcomes were duration of invasive and total ventilation (days), reintubation or tracheostomyrates, and survival.
Results:  Among 364 randomized patients (mean age, 63.1[SD, 14.8] years; 50.5% male), 319 were evaluable for the primary effectiveness outcome (41 died before liberation, 2 withdrew, and 2 were discharged with ongoing ventilation). The median time to liberation was 4.3 days in the non-invasive group vs 4.5 days in the invasive group (adjusted hazard ratio, 1.1; 95% CI, 0.89-1.40).Competing risk analysis accounting for deaths had a similar result (adjusted hazard ratio, 1.1; 95% CI, 0.86-1.34). The non-invasive group received less invasive ventilation (median, 1 day vs 4 days; incidence rate ratio, 0.6; 95%CI, 0.47-0.87) and fewer total ventilator days (median, 3 days vs 4 days;incidence rate ratio, 0.8; 95% CI, 0.62-1.0). There was no significant difference in reintubation, tracheostomy rates, or survival. Adverse events occurred in 45 patients (24.7%) in the non-invasive group compared with 47(25.8%) in the invasive group.
Conclusions and Relevance:  Among patients requiring mechanical ventilation in whom a spontaneous breathing trial had failed, early extubation to non-invasive ventilation did not shorten time to liberation from any ventilation.
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Critical Care Reviews Newsletter 348 12th August 2018

The 348th Critical Care Reviews Newsletter, brings you the best critical care research and open access articles from across the medical literature during the last week.  “The highlights of this week’s edition are randomised controlled trials on terlipressin versus noradrenaline for AKI in acute-on-chronic liver failure, restricted fluid bolus volume in early paediatric septic shock & early CPAP in acute respiratory failure in children with impacritcal care reviewsired immunity; systematic reviews and meta analyses on complications and failures of central vascular access devices & laryngeal injury and upper airway symptoms after intubation during critical care; and guidelines and position statements on steroid therapy for sepsis, disorders of consciousness & spinal motion restriction in trauma.”

The full text of the newsletter can be accessed via this link.

High‐flow nasal cannulae for respiratory support in adult intensive care patients

This systematic review produced by Corley and colleagues was published online in Cochrane Library in May 2017.

Backcochrane-57-1ground:  A common reason for intensive care unit (ICU) admission is the need for breathing (or respiratory) support. HFNC are small plastic tubes that sit inside the nostrils and deliver a heated mix of air and oxygen at high flow rates to patients requiring breathing support. They are used frequently in the ICU, yet no clear evidence shows whether they provide patients with long-term benefits such as reduced ICU stay or improved chances of survival.

Study characteristics:  The evidence is current to March 2016. We included in the review 11 studies with 1972 participants. Most participants had respiratory failure, or had just been taken off an artificial breathing machine. Included studies compared HFNC with low-flow oxygen given through face masks, through low-flow cannulae, or through devices that use mild pressure to aid oxygen delivery. We reran the search in December 2016 and will deal with any studies of interest when we update the review.

Key results:  We found no evidence that HFNC reduced the rate of treatment failure or risk of death compared with low-flow oxygen devices. We found no evidence of any advantages for HFNC in terms of adverse event rates, ICU length of stay, or duration of respiratory support. We observed no differences in participants’ blood oxygen levels or carbon dioxide blood levels, and we noted that any differences in breathing rates were small and were not considered clinically important. Studies reported no differences in patient-rated measures of comfort. Only one study found evidence of less dry mouth when HFNC was used.

Quality of evidence:  Most studies had reported methods inadequately, and we did not know whether risk of bias may have affected study results. We identified few eligible studies and noted some differences among participants within our included studies, particularly in reasons for requiring respiratory support. We used the GRADE system to rate the evidence for each of our outcomes, and we judged all evidence to be of low or very low quality.

Conclusion:  We were not able to collect sufficient evidence from good quality studies to determine whether HFNC offer a safe and effective way of delivering respiratory support for adults in the ICU.

The full text of the review can be accessed via this link to the Cochrane Library.

Management of hypoxaemic respiratory failure in a Respiratory High-dependency Unit.

This paper was published by Hukins and colleagues in Internal Medicine Journal in July 2017 volume 47 number 7 addressing the limited data on outcomes of hypoxaemic respiratory failure (HRF), especially in non-intensive care unit (ICU) settings.


Aim:  To assess outcomes in HRF (without multi-system disease and not requiring early intubation) of patients directly admitted to a Respiratory High-dependency Unit (R-HDU).

Methods:  This is a retrospective cohort study of HRF compared to hypercapnic respiratory failure (HCRF) in a R-HDU (2007-2011). Patient characteristics (age, gender, pre-morbid status, diagnoses) and outcomes (non-invasive ventilation (NIV) use, survival, ICU admission) were assessed. 

Results:  There were 1207 R-HDU admissions in 2007-2011, 205 (17%) with HRF and 495 (41%) with HCRF. The proportion with HRF increased from 12.2% in 2007 to 20.1% in 2011 (P < 0.05). HRF patients were younger, more often male and had better pre-morbid performance. Compared to HCRF, HRF was more frequently associated with lung consolidation (61% vs 15%, P < 0.001), interstitial lung disease (12% vs 1%, P < 0.001) and pulmonary hypertension (7% vs 0%, P < 0.001) and less frequently with chronic obstructive pulmonary disease (24% vs 65%, P < 0.001) and obstructive sleep apnoea (8% vs 26%, P < 0.001). Fewer patients with HRF were treated with NIV (28% vs 87%, P < 0.001), but NIV was discontinued early more often (28% vs 7%, P < 0.001). A total of 18% with HRF was transferred to ICU compared to 6% with HCRF (P = 0.06). More patients with HRF died (19.5% vs 12.3%, P = 0.02). Interstitial lung disease, consolidation, shock, malignancy and poorer pre-morbid function were associated with increased mortality.

Conclusions:  Initial R-HDU management is an effective option in selected HRF to reduce ICU demand, although mortality and clinical deterioration despite NIV are more common than in HCRF.

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Latest Issue of “Intensive Care Medicine” Volume 43 Number 4

To access Intensive Care Medicine’s latest issue’s contents page follow this link.

Articles in this issue include “Targeted temperature management after intraoperative cardiac arrest: a multicenter retrospective study”, “Clinical characteristics and predictors of mortality in cirrhotic patients with candidemia and intra-abdominal candidiasis: a multicenter study” and “Extracorporeal carbon dioxide removal (ECCO2R) in patients with acute respiratory failure”.

To access the full text of these articles from the journal’s homepage requires a personal subscription to the journal.  Individual articles can be ordered via the Rotherham NHS Foundation Trust Library and Knowledge Service.  Registered members of the library can make article requests online via this link.

The full text of articles from issues older than one year ago is available via this link to an archive of issues of Intensive Care Medicine.  A Rotherham NHS Athens password is required.  Eligible staff can register for an Athens password via this link.  Please speak to the library staff for more details.

Use of noninvasive ventilation in immunocompromised patients with acute respiratory failure

Huang, H-B et al. Critical Care. 21:4

Background: Acute respiratory failure (ARF) remains a common hazardous complication in immunocompromised patients and is associated with increased mortality rates when endotracheal intubation is needed. We aimed to evaluate the effect of early noninvasive ventilation (NIV) compared with oxygen therapy alone in this patient population.


Conclusions: The limited evidence indicates that early use of NIV could reduce short-term mortality in selected immunocompromised patients with ARF. Further studies are needed to identify in which selected patients NIV could be more beneficial, before wider application of this ventilator strategy.

Read the full abstract and article here 

Long-Term Survival Rate in Patients With Acute Respiratory Failure Treated With Noninvasive Ventilation in Ordinary Wards

Cabrini, L. et al. Critical Care Medicine. Published online: 4 August 2016

Image source: Samir – Wikipedia // CC BY-SA 3.0

Image shows chest X-ray of a patient with ARDS.

Objective: Noninvasive ventilation is a life-saving technique increasingly used to treat acute respiratory failure. Noninvasive ventilation has been applied mostly in ICUs, but several reasons brought to an increasing application of noninvasive ventilation in ordinary wards. Few articles evaluated the outcomes of patients receiving noninvasive ventilation including long-term follow-up. The aim of the present study was to assess 1-year survival rate of patients treated with noninvasive ventilation outside the ICU for acute respiratory failure of heterogeneous causes and to identify the predictors of long-term mortality.

Design: Prospective, observational, pragmatic study.

Setting: Ordinary wards of a teaching hospital.

Patients: Consecutive patients treated with noninvasive ventilation for acute respiratory failure.

Measurements and Main Results: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with “do-not-resuscitate” status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses.

Conclusions: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.

Read the abstract here