Critical Care Reviews Newsletter 428 23rd February 2020

The Critical Care Reviews Newsletter, bringing you the best critical care research and open access articles from across the medical literature over the past seven days.
The highlights of this week’s edition are randomised controlled trials on a driving pressure-limited strategy for ARDS & intrapulmonary concentrations of meropenem administered by continuous infusion; systematic reviews and meta analyses on neuromuscular blocking agent use in ARDS & the effect of continuous epinephrine infusion on survival in critically ill patients; and observational studies on the association of low baseline diaphragm muscle mass with prolonged mechanical ventilation and mortality among critically ill adults & a post hoc analysis of ANDROMEDA-SHOCK trial – capillary refill time status could identify different clinical phenotypes among septic shock patients fulfilling Sepsis-3 criteria.
There are also two guidelines on nutrition, in critically ill children & in acute pancreatitis, as well as a guideline on the management of adult acute and acute-on-chronic liver failure in the ICU. There are narrative reviews on airway pressure release ventilation & community-acquired pneumonia in critically ill very old patients; editorials on stress ulcer prophylaxis & intensive care during the coronavirus epidemic; and commentaries on ECMO for COVID-19-induced respiratory failure & what has been learned in responding to emerging zoonotic viruses; as well as correspondence on Immune biomarker-based enrichment in sepsis trials & plasma-first resuscitation to treat haemorrhagic shock in urban areas. 
The full text of the newsletters is available via this link.

Society of Critical Care Medicine’s Congress 2020

This supplement contains the major trial results, and the text of a plenary lecture, presented and simultaneously published at the Society of Critical Care Medicine’s 49th Critical Care Congress in Orlando during February 2020.
The full text of the newsletters is available via this link.

Critical Care Reviews Meeting January 2020

This supplemental newsletter contains information from the Critical Care Reviews Meeting. There are links to the trial papers and associated editorials, as well as the recorded meeting presentations, for each of the IHME Sepsis Study, PEPTIC and VITAMINS trials. The 65 trial is accepted and due for publication in a couple of weeks – the link to its presentation video is included. All other meeting talks have been recorded and will be available over the coming weeks.
The full text of the newsletters is available via this link.

Coronavirus disease (COVID-19) outbreak; WHO website

On the World Health Organisation’s designated website you can find information and guidance from WHO regarding the current outbreak of coronavirus disease (COVID-19) that was first reported from Wuhan, China, on 31 December 2019. Please visit this page for daily updates.
Link to WHO Coronavirus disease outbreak website
WHO is working closely with global experts, governments and partners to rapidly expand scientific knowledge on this new virus, to track the spread and virulence of the virus, and to provide advice to countries and individuals on measures to protect health and prevent the spread of this outbreak.

Spiritual care in the intensive care unit: An integrative literature research

This research by Willemse et al was first published in the Journal of Critical Care during January 2020.
Purpose:  The aim of this study is to review the literature for three major domains in relation to spiritual care in the ICU, namely Quality of Life (QoL), Quality of Care (QoC), and Education (E).
Method:  An integrative literature research.
Results:  The 113 selected articles reveal that spirituality is an essential component of QoL and that complementary and effective spiritual care (SC) relieves distress of patients and their relatives. Furthermore, the contribution of SC to quality of care is: 1) diagnosing and addressing spiritual and emotional needs among patients and their relatives; 2) offering spiritual comfort to the patient in distress; 3) increased spiritual well-being of both patients and their relatives; 4) increased family satisfaction in general and by shared decision-making.
Finally, the literature reveals the necessity to improve SC knowledge and skills of ICU healthcare professionals (IC HCPs) through relevant training courses.
Conclusion:  SC contributes to QoL and QoC. The literature indicates that IC HCPs acknowledge the need to improve their SC knowledge and skills to enhance complementary, effective SC. Further research on SC as an integrated part of daily ICU care is necessary to improve QoL and QoC of patients and their relatives.
The full text of this article is available to subscribers via this link to the journal’s homepage.  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.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.

This article by Huang and colleagues was first published in the Lancet in January 2020.
Background:  A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients.
Methods:  All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not.
Findings:  By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0-58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0-13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα.
Interpretation:  The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies.
Funding:  Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
The full text of this article is freely available via this link.  The print copy of this issue of the Lancet is available in the Healthcare Library on D Level of Rotherham General Hospital.

Effect of Stress Ulcer Prophylaxis With Proton Pump Inhibitors vs Histamine-2 Receptor Blockers on In-Hospital Mortality Among ICU Patients Receiving Invasive Mechanical Ventilation: The PEPTIC Randomized Clinical Trial.

This article by the PEPTIC Investigators for the Australian and New Zealand Intensive Care Society Clinical Trials Group, Alberta Health Services Critical Care Strategic Clinical Network, and the Irish Critical Care Trials Group was published in JAMA.
Importance:  Proton pump inhibitors (PPIs) or histamine-2 receptor blockers (H2RBs) are often prescribed for patients as stress ulcer prophylaxis drugs in the intensive care unit (ICU). The comparative effect of these drugs on mortality is unknown.
Objective:  To compare in-hospital mortality rates using PPIs vs H2RBs for stress ulcer prophylaxis.
Design, Setting, and Participants:  Cluster crossover randomized clinical trial conducted at 50 ICUs in 5 countries between August 2016 and January 2019. Patients requiring invasive mechanical ventilation within 24 hours of ICU admission were followed up for 90 days at the hospital.
Interventions:  Two stress ulcer prophylaxis strategies were compared (preferential use with PPIs vs preferential use with H2RBs). Each ICU used each strategy sequentially for 6 months in random order; 25 ICUs were randomized to the sequence with use of PPIs and then use of H2RBs and 25 ICUs were randomized to the sequence with use of H2RBs and then use of PPIs (13 436 patients randomized by site to PPIs and 13 392 randomized by site to H2RBs).
Main Outcomes and Measures:  The primary outcome was all-cause mortality within 90 days during index hospitalization. Secondary outcomes were clinically important upper gastrointestinal bleeding, Clostridioides difficile infection, and ICU and hospital lengths of stay.
Results:  Among 26 982 patients who were randomized, 154 opted out, and 26 828 were analyzed (mean [SD] age, 58 [17.0] years; 9691 [36.1%] were women). There were 26 771 patients (99.2%) included in the mortality analysis; 2459 of 13 415 patients (18.3%) in the PPI group died at the hospital by day 90 and 2333 of 13 356 patients (17.5%) in the H2RB group died at the hospital by day 90 (risk ratio, 1.05 [95% CI, 1.00 to 1.10]; absolute risk difference, 0.93 percentage points [95% CI, -0.01 to 1.88] percentage points; P = .054). An estimated 4.1% of patients randomized by ICU site to PPIs actually received H2RBs and an estimated 20.1% of patients randomized by ICU site to H2RBs actually received PPIs. Clinically important upper gastrointestinal bleeding occurred in 1.3% of the PPI group and 1.8% of the H2RB group (risk ratio, 0.73 [95% CI, 0.57 to 0.92]; absolute risk difference, -0.51 percentage points [95% CI, -0.90 to -0.12 percentage points]; P = .009). Rates of Clostridioides difficile infection and ICU and hospital lengths of stay were not significantly different by treatment group. One adverse event (an allergic reaction) was reported in 1 patient in the PPI group.
Conclusions and Relevance:  Among ICU patients requiring mechanical ventilation, a strategy of stress ulcer prophylaxis with use of proton pump inhibitors vs histamine-2 receptor blockers resulted in hospital mortality rates of 18.3% vs 17.5%, respectively, a difference that did not reach the significance threshold. However, study interpretation may be limited by crossover in the use of the assigned medication.
The print copy of this issue of JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Effect of Vitamin C, Hydrocortisone, and Thiamine vs Hydrocortisone Alone on Time Alive and Free of Vasopressor Support Among Patients With Septic Shock: The VITAMINS Randomized Clinical Trial.

This research by Fujii and other was first published in JAMA during January 2020
Importance:  It is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.
Objective:  To determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock.
Design, Setting, and Participants:  Multicenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.
Interventions: Patients were randomized to the intervention group (n = 109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n = 107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days.
Main Outcomes and Measures:  The primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were pre-specified, including 90-day mortality.
Results:  Among 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P = .83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported.
Conclusions and Relevance:  In patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Efficacy and safety of gastrointestinal bleeding prophylaxis in critically ill patients: systematic review and network meta-analysis.

This article by Wang and others was published online in the BMJ during January 2020
Objective:  To determine, in critically ill patients, the relative impact of proton pump inhibitors (PPIs), histamine-2 receptor antagonists (H2RAs), sucralfate, or no gastrointestinal bleeding prophylaxis (or stress ulcer prophylaxis) on outcomes important to patients.
Design:  Systematic review and network meta-analysis.
Data Sources:  Medline, PubMed, Embase, Cochrane Central Register of Controlled Trials, trial registers, and grey literature up to March 2019.
Eligibility Criteria For Selecting Studies and Methods:  We included randomised controlled trials that compared gastrointestinal bleeding prophylaxis with PPIs, H2RAs, or sucralfate versus one another or placebo or no prophylaxis in adult critically ill patients. Two reviewers independently screened studies for eligibility, extracted data, and assessed risk of bias. A parallel guideline committee (BMJ Rapid Recommendation) provided critical oversight of the systematic review, including identifying outcomes important to patients. We performed random-effects pairwise and network meta-analyses and used GRADE to assess certainty of evidence for each outcome. When results differed between low risk and high risk of bias studies, we used the former as best estimates.
Results:  Seventy two trials including 12 660 patients proved eligible. For patients at highest risk (>8%) or high risk (4-8%) of bleeding, both PPIs and H2RAs probably reduce clinically important gastrointestinal bleeding compared with placebo or no prophylaxis (odds ratio for PPIs 0.61 (95% confidence interval 0.42 to 0.89), 3.3% fewer for highest risk and 2.3% fewer for high risk patients, moderate certainty; odds ratio for H2RAs 0.46 (0.27 to 0.79), 4.6% fewer for highest risk and 3.1% fewer for high risk patients, moderate certainty). Both may increase the risk of pneumonia compared with no prophylaxis (odds ratio for PPIs 1.39 (0.98 to 2.10), 5.0% more, low certainty; odds ratio for H2RAs 1.26 (0.89 to 1.85), 3.4% more, low certainty). It is likely that neither affect mortality (PPIs 1.06 (0.90 to 1.28), 1.3% more, moderate certainty; H2RAs 0.96 (0.79 to 1.19), 0.9% fewer, moderate certainty). Otherwise, results provided no support for any affect on mortality, Clostridium difficile infection, length of intensive care stay, length of hospital stay, or duration of mechanical ventilation (varying certainty of evidence).
Conclusions:  For higher risk critically ill patients, PPIs and H2RAs likely result in important reductions in gastrointestinal bleeding compared with no prophylaxis; for patients at low risk, the reduction in bleeding may be unimportant. Both PPIs and H2RAs may result in important increases in pneumonia. Variable quality evidence suggested no important effects of interventions on mortality or other in-hospital morbidity outcomes.
The full text of this article is freely available via this link.