Journal of Critical Care Volume 59 October 2020

The latest issue of this journal was published online in September 2020.  The contents include the following articles:  “High-flow tracheal oxygen in tracheostomised COVID-19 patients, “Clinically significant anticardiolipin antibodies associated with COVID-19” and “Adjunctive therapy with vitamin c and thiamine in patients treated with steroids for refractory septic shock: A propensity matched before-after, case-control study”.
The full text of all these articles is freely available from the journals contents page.

Critical Care Reviews Newsletter 458 20th September 2020

The Critical Care Reviews Newsletter brings you the best critical care research and open access articles from across the medical literature over the previous week.
The highlights of this week’s edition are randomised controlled trials on antithrombin supplementation during extracorporeal membrane oxygenation and the effect of aspirin on deaths associated with sepsis in healthy older people; systematic reviews and meta analyses on high-flow nasal oxygen during the intraoperative period & polymyxin B-immobilized hemoperfusion for sepsis and septic shock; and observational studies on intra-arrest transport vs continued on-scene resuscitation in patients with out-of-hospital cardiac arrest and a prognostic score for 1-year unplanned rehospitalization or death of adult sepsis survivors. There are also guidelines on nutrition management for critically and acutely unwell hospitalised patients with COVID-19 and  the conduct of observational critical care research for the COVID-19 pandemic and beyond; narrative reviews on acute ischemic stroke and anticoagulation strategies in extracorporeal circulatory devices; editorials on vitamin C and thiamine for sepsis and severe COVID-19 infections; and commentaries on how i select which patients with ARDS should be treated with venovenous ECMO and delivering options for preventing and treating COVID-19.
The full text of the issue is available via this link

Assessment of fluid resuscitation on time to hemodynamic stability in obese patients with septic shock

This research by Kiracofe and colleagues was published on line in the Journal of Critical Care during September 2020.
Purpose:  Assess time to hemodynamic stability (HDS) in obese patients with septic shock who received <30 vs. ≥30 ml/kg of initial fluid resuscitation based on actual body weight (ABW).
Materials and methods:  Multicenter, retrospective, cohort analysis of 322 patients.
Results:  Overall 216 (67%) patients received <30 ml/kg of initial fluid resuscitation. Initial fluid received was lower in the <30 ml/kg vs. ≥30 ml/kg group (16 vs. 37 ml/kg). The ≥30 ml/kg group had shorter time to HDS (multivariable p = 0.038) and lower riskof in-hospital death (multivariable p = 0.038). An exploratory subgroup analysis (n = 227) was performed, classifying patients by dosing strategy [ABW, adjusted body weight (AdjBW), ideal body weight (IBW)] based on fluid received at 3 h divided by 30 mL/kg. ABW dosed patients had a shorter time to HDS (multivariable p = 0.013) and lower risk of in-hospital death (multivariable p = 0.008) vs. IBW. Similar outcomes were observed between ABW vs. AdjBW.
Conclusions:  Obese patients given ≥30 ml/kg based on ABW had a shorter time to HDS and a lower risk of in-hospital death. Exploratory results suggest improved outcomes resuscitating by ABW vs. IBW; ABW showed no strong benefit over AdjBW. Further prospective studies are needed to confirm the optimal fluid dosing in obese patients.
The full text of this article is freely available to all via this link.

Effectiveness of polymyxin B-immobilized hemoperfusion against sepsis and septic shock: A systematic review and meta-analysis

This article by Xiaoming Li and other researchers was published online in the Journal of Critical Care during September 2020.
Purpose:  To evaluate the efficacy and safety of Polymyxin B-immobilized hemoperfusion (PMX-HP) against sepsis or septic shock.
Methods:  We searched databases (PubMed, EMBASE and Cochrane Library) to identify eligible randomized controlled trials (RCTs). The primary outcomes we included in this review were mortality at the longest follow-up available and serious adverse events associated with treatments. We used the Cochrane risk of bias assessment tool to evaluate risk of bias. Trial Sequential Analysis (TSA) was performed to assess the conclusion reached in our research.
Results:  Thirteen studies including 1163 patients were identified. Use of PMX-HP could reduce overall mortality [relative risk (RR) 0.68, 95% confidence interval (CI) 0.51–0.91, P = 0.01]. An interesting finding was that the mortality of patients in Acute Physiology and Chronic Health Evaluation (APACHE II) scores <25 group (RR 0.64, 95% CI 0.52–0.78, P < 0.0001) and sepsis group (RR 0.48, 95% CI 0.32–0.72, P = 0.0003) significantly decreased after PMX-HP treatment. The result also showed that PMX-HP could reduce endotoxin levels [Standardized mean difference (SMD) -1.53, 95% CI -2.92– -0.13, P = 0.03] and improve mean arterial pressure (SMD 1.07, 95% CI 0.14–2.01, P = 0.02). Serious adverse events between the PMX-HP group and standard therapy group were not significantly different (RR 2.16, 95% CI 0.97–4.80, I2 = 0%, P = 0.06). However, TSA did not provide conclusive evidence and more high quality RCTs were required.
Conclusion:  Using PMX-HP to treat patients with less severe sepsis can reduce overall mortality and is safe. Treatment efficacy may benefit from the reduction of endotoxin level and the improvement of hemodynamics. More high quality RCTs are required to further evaluate the clinical role of PMX-HP against severe sepsis or septic shock.
The full text of this article is freely available to all via this link.

Critical Care Reviews Newsletter 457 19th September 2020

Welcome to the 457th Critical Care Reviews Newsletter, bringing you the best critical care research and open access articles from across the medical literature last week.
The highlights of this edition are randomised controlled trials on out-of-hospital tranexamic acid for traumatic brain injury, high-flow oxygen with capping or suctioning for tracheostomy decannulation and recombinant human granulocyte colony–stimulating factor for patients with COVID-19 and lymphopenia; systematic reviews and meta analyses on prediction of poor neurological outcome in comatose survivors of cardiac arrest  and the effect of delayed appropriate antibiotic treatment on the outcomes of patients with severe bacterial infections; and observational studies on Inappropriate empirical antibiotic therapy for bloodstream infections & the prevalence and course of frailty in survivors of critical illness.
There are also guidelines on management of intravascular catheters & adult ICU triage during the COVID-19 pandemic; narrative reviews on nasal high flow oxygen during acute respiratory failure & allergy and anaesthesia; an editorial on reassuring the public and clinical community about a COVID-19 vaccine; and commentaries on bacterial and fungal superinfections in critically ill patients with COVID-19 and COVID-19 and the path to immunity; as well as correspondence on the interaction between arterial oxygenation and carbon dioxide and hospital mortality following out of hospital cardiac arrest and MSC-derived exosomes for ECMO-supported ARDS.
The full text of the issue is available via this link

Critical Care Reviews Newsletter 456 6th September 2020

The Critical Care Reviews Newsletter lists the best critical care research and open access articles from across the medical literature over the past week.
The highlights of this week’s edition are several fascinating randomised controlled trials on intraoperative low tidal volume vs conventional tidal volume, azithromycin for severe COVID-19, midodrine for persistent hypotension in the ICU, NAVA in acute respiratory failure and preoperative intravenous iron to treat anaemia before major abdominal surgery.
The full text of the issue is available via this link

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

This article by the Writing Committee for the REMAP-CAP Investigators was first published online in JAMA in September 2020.
Importance:  Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited.
Objective:  To determine whether hydrocortisone improves outcome for patients with severe COVID-19.
Design, Setting, and Participants:  An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020.InterventionsThe corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108).
Main Outcomes and Measures:  The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%).
Results:  After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively.
Conclusions and Relevance:  Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.

Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis.

This article by researchers as part of the PregCOV-19 Living Systematic Review Consortium was first published in the online edition of the BMJ during September 2020.
Objective:  To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).
Design:  Living systematic review and meta-analysis.
Data Sources:  Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 26 June 2020, along with preprint servers, social media, and reference lists.
Study Selection:  Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.
Data Extraction:  At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.
Results:  77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I2=74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I2=0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I2=0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19.
Conclusion:  Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease.
Reader’ Note:  This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.
The full text of this article is available via this link.  The paper copy of the BMJ is also available on D Level of the hospital.

Effect of Dexamethasone on Days Alive and Ventilator-Free in Patients with Moderate or Severe Acute Respiratory Distress Syndrome and COVID-19: The CoDEX Randomized Clinical Trial.

This article by the COALITION COVID-19 Brazil III Investigators was first published in JAMA online in September 2020.
Importance:  Acute respiratory distress syndrome (ARDS) due to coronavirus disease 2019 (COVID-19) is associated with substantial mortality and use of health care resources. Dexamethasone use might attenuate lung injury in these patients.
Objective:  To determine whether intravenous dexamethasone increases the number of ventilator-free days among patients with COVID-19-associated ARDS.
Design, Setting, and Participants:  Multicenter, randomized, open-label, clinical trial conducted in 41 intensive care units (ICUs) in Brazil. Patients with COVID-19 and moderate to severe ARDS, according to the Berlin definition, were enrolled from April 17 to June 23, 2020. Final follow-up was completed on July 21, 2020. The trial was stopped early following publication of a related study before reaching the planned sample size of 350 patients.
Interventions:  Twenty mg of dexamethasone intravenously daily for 5 days, 10 mg of dexamethasone daily for 5 days or until ICU discharge, plus standard care (n =151) or standard care alone (n = 148).
Main Outcomes and Measures:  The primary outcome was ventilator-free days during the first 28 days, defined as being alive and free from mechanical ventilation. Secondary outcomes were all-cause mortality at 28 days, clinical status of patients at day 15 using a 6-point ordinal scale (ranging from 1, not hospitalized to 6, death), ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, and Sequential Organ Failure Assessment (SOFA) scores (range, 0-24, with higher scores indicating greater organ dysfunction) at 48 hours, 72 hours, and 7 days.
Results:  A total of 299 patients (mean [SD] age, 61 [14] years; 37% women) were enrolled and all completed follow-up. Patients randomized to the dexamethasone group had a mean 6.6 ventilator-free days (95% CI, 5.0-8.2) during the first 28 days vs 4.0 ventilator-free days (95% CI, 2.9-5.4) in the standard care group (difference, 2.26; 95% CI, 0.2-4.38; P = .04). At 7 days, patients in the dexamethasone group had a mean SOFA score of 6.1 (95% CI, 5.5-6.7) vs 7.5 (95% CI, 6.9-8.1) in the standard care group (difference, -1.16; 95% CI, -1.94 to -0.38; P = .004). There was no significant difference in the prespecified secondary outcomes of all-cause mortality at 28 days, ICU-free days during the first 28 days, mechanical ventilation duration at 28 days, or the 6-point ordinal scale at 15 days. Thirty-three patients (21.9%) in the dexamethasone group vs 43 (29.1%) in the standard care group experienced secondary infections, 47 (31.1%) vs 42 (28.3%) needed insulin for glucose control, and 5 (3.3%) vs 9 (6.1%) experienced other serious adverse events.
Conclusions and Relevance:  Among patients with COVID-19 and moderate or severe ARDS, use of intravenous dexamethasone plus standard care compared with standard care alone resulted in a statistically significant increase in the number of ventilator-free days (days alive and free of mechanical ventilation) over 28 days.
The full text of this article is freely available via this link.  The paper copy of the article is available in the Healthcare Library on D Level of Rotherham Hospital.

Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial.

This article by participants in the CAPE COVID Trial Group and the CRICS-TriGGERSep Network was published in JAMA in September 2020.
Importance:  Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option.
Objective:  To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure.
Design, Setting, and Participants:  Multi-centre randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board.
Interventions:  Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73).
Main Outcomes and Measures:  The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay.
Results:  The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment.
Conclusions and Relevance:  In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome.
The print copy of this issue JAMA is available in the Healthcare Library on D Level of Rotherham General Hospital.