Author Archives: nsilvey

I have to admit choosing this week’s #twitjc paper because of a particular annoyance of mine. That annoyance is seeing a patient’s IV fluid rota with litres and litres of 0.9% normal saline written up for days on end. I have always been a fan of the phrase “there is nothing normal about normal saline” and have always been wary of the risk of hyperchloraemic acidosis from giving chloride rich fluids like 0.9% normal saline. Do chloride rich fluids do harm to patients?

In October 2012 a paper was published in JAMA which on the surface appears to support my dislike of normal saline. The study, entitled Association Between a Chloride-Liberal vs Chloride-Restrictive Intravenous Fluid Administration Strategy and Kidney Injury in Critically Ill Adults, was designed to assess the association of a chloride-restrictive vs chloride-liberal IV fluid strategy and acute kidney injury in critically ill patients. This was a prospective, open-label, sequential study comparing 760 patients admitted to an ICU during a control period with 773 patients admitted to the same ICU at a university hospital in Melbourne.

During the control period patients received standard IV fluids, there was then a phase out period before the intervention period during which any use of chloride-rich fluids (0.9% saline, 4% succinylated gelatin solution or 4% albumin solution) was restricted to specialist approval. Instead patient’s received a Hartmann solution, Plasma-Lyte  48 and chloride-poor 20% albumin solution. The primary outcome measures included increase from baseline to peak creatinine level in the ICU and incidence of AKI according to the RIFLE classification. Secondary measures including the need for renal replacement therapy, length of stay in ICU and hospital and survival.

The results:

- Chloride administration decreased from 694 to 496mmol/patient from the control to intervention period

- Mean serum creatinine level increase was 22.6 vs 14.8µmol/L from the control to intervention period (p=0.03)

- The incidence of injury and failure class of RIFLE-defined AKI was 14% in the control period vs 6.3% in the   intervention period (p=<0.001)

- The use of renal replacement therapy was 10% in the control period vs 6.3% in the intervention period (p=0.005)

The author’s conclusions:

The implementation of a chloride-restrictive strategy in a tertiary ICU was associated with a significant decrease in the incidence of AKI and use of RRT

So this appears to support my dislike of giving litres of 0.9% saline to patients. But is it that simple and is this study that clear cut? As this study is not without its controversies it is a perfect paper to discuss in this Sunday’s #twitjc. Discussion points will be posted soon and I look forward to a lively discussion of an extremely interesting paper.

A huge thank you to the wonderful @paedssho for writing this week’s summary – I am currently on a run of seven nights in ED and have handed over the journal club this week to David….

This week finds #twitjc back in intensive care, with a paper from the New England Journal of Medicine:

“High-Frequency Oscillation in Early Acute Respiratory Distress Syndrome”
The OSCILLATE trial

The acute respiratory distress syndrome (ARDS) is a common complication of critical illness. Although mechanical ventilation is a key part of the management of ARDS, it can perpetuate lung injury; either through barotrauma or atelectotrauma. Previous trials have found decreased mortality when using smaller tidal volumes and higher PEEP when using conventional mechanical ventilation. However, morbidity and mortality from ARDS remain high, and other approaches warrant further investigation.

One such approach is high-frequency oscillatory ventilation (HFOV), which delivers very small tidal volumes at very high rates (3 to 15 breaths per second). Previous randomised trials of the use of HFOV in adults with ARDS have suggested that it results in improvements in oxygenation and survival, but the trials were limited by small sample sizes and outdated ventilation strategies for the control group.

The OSCILLATE trial compared HFOV with conventional ventilation (using low tidal volumes and high PEEP) in patients with new-onset, moderate-to-severe ARDS. After an initial period on conventional ventilation, patients were then randomised to receive either HFOV or to continue on the conventional ventilator settings. The primary outcome was the rate of in-hospital death from any cause. Secondary outcomes included refractory hypoxia, duration of ventilation, and length of ICU stay.

The trial had intended to recruit 1200 patients; however, the trial was stopped early after 548 had undergone randomisation.

•In-hospital mortality was 47% in the HFOV group, as compared with 35% in the control group (relative risk of death with HFOV, 1.33; 95% confidence interval, 1.09 to 1.64; P=0.005)

The authors concluded:

“In adults with moderate-to-severe ARDS, early application of HFOV, as compared with a ventilation strategy of low tidal volume and high positive end-expiratory pressure, does not reduce, and may increase, in-hospital mortality.”

These findings were reproduced in a second trial, OSCAR, published in the same issue of NEJM. Does this spell trouble for HFOV in ARDS? Does the methodology stand up to scrutiny? And should this paper, along with OSCAR, change our practice?

Join us on Sunday 10th March at 8pm for a discussion of this paper. Full-text can be found via the ever-brilliant Now@NEJM blog.

http://blogs.nejm.org/now/index.php/new-evidence-that-high-frequency-oscillation-not-beneficial-for-ards-patients-and-may-even-be-harmful/2013/02/27/

Was the methodology of this study appropriate to answer the clinical question?

Were the outcomes, both primary and secondary, appropriate?

All patients underwent an endoscopy within 6 hours. Are the results of this trial applicable in other centres where patients may not undergo an endoscopy so quickly?
Should we be using a restrictive approach to blood transfusions in upper GI bleeds?

A patient is brought into resus vomiting up fresh red blood. The team jump into action, assessing the patient and diagnosing an upper GI bleed, gaining intravenous access, taking blood samples and taking a sample for a cross-match. Does this patient require an emergency blood transfusion?

Before we prescribe a unit of packed red cells to a patient there is a lot to think about. Why does this patient need a transfusion? Are we giving them the right blood product? Is there an alternative to transfusion? What are the potential risks to the patient of giving them a transfusion? Are we using a valuable resource in the right way? Giving a blood transfusion can be lifesaving but it is not without its risks.

If a patient is haemodynamically unstable and is exsanguinating the decision to transfuse is a simple one. But most upper GI bleeds are not as severe as this. When should we be transfusing such patients? This is a question a recent paper published in the NEJM set out to answer.

In the study 921 patients presenting with upper GI bleeds were randomised in one centre in Barcelona into two groups:

1. In the restrictive transfusion group the haemoglobin threshold was 7g/dL with a target range for the post transfusion Hb of 7 to 9
2. In the liberal transfusion group the Hb threshold was 9g/dL with a target range for the post transfusion Hb of 9 to 11

All patients underwent emergency gastroscopy within the first 6 hours and received treatment as appropriate for the underlying cause of their GI bleed.  The primary outcome was the rate of death from any cause within the first 45 days. Secondary outcomes included the rate of further bleeding and the rate of in-hospital complications.

The results:

• Mortality at 45 days was significant lower in the restrictive strategy group than in the liberal strategy group: 5% compared to 9% (p=0.02). The risk of death was virtually unchanged after adjustment for baseline risk factors for death
• The rate of further bleeding was significantly lower in the restrictive strategy group than in the liberal strategy group: 10% compared to 16% (p=0.01)

The author’s conclusions:

…we found that a restrictive transfusion strategy, as compared with a liberal transfusion strategy, improved the outcomes among patients with acute upper GI bleeding…. Our results suggest that in patients with acute gastrointestinal bleeding, a strategy of not performing transfusion until the haemoglobin concentration falls below 7g per decilitre is a safe and effective approach

I look forward to discussing this paper on Sunday night at 8pm. A link to the free full text can be found at the excellent Now@NEJM blog

The Twitter Journal Club returns for 2013 on 20th January and our first paper of 2013 will be….

Transfusion Strategies for Acute Upper Gastrointestinal Bleeding

Look out for the paper summary which will follow very soon and remember to join in at 8pm on the 20th

1. Was the methodology of this study appropriate to answer the clinical question?

2. This study was dramatically underpowered & its results combined with the WARFASA trial. Does this affect how we view its results?

3. Is the pooled data from the ASPIRE& WARFASA trials enough to support the use of aspirin therapy in patient’s with unprovoked VTE post full anticoagulation?

Go into any medical ward in a hospital, open up all the drug charts in a bay of patients and you will find aspirin prescribed. Aspirin is extremely widely used, I don’t think an oncall has ever gone by in which I haven’t admitted a patient who takes aspirin. From patients who take it after having a heart attack to patients who take it after reading a newspaper report hailing its health benefits it is one of the most common drugs taken regularly. However recently in some circles its use has fallen out of favour. Once widely used for thromboprophylaxis in AF there is now a consensus that aspirin should no longer be used for this indication.

But what about its use in patients who have already had a venous thromboembolic event – i.e. a PE or DVT? Is there any evidence to support its use as anticoagulation therapy?

The WARFASA trial, published in the NEJM in May 2012, examined the role of aspirin after patients with VTE’s had completed 6-18 months of warfarin therapy. This study looking at 402 patients showed aspirin significantly reduced recurrent VTE (6.6% vs. 11.2%, p=0.02, HR 0.58, NNT 21). A sister trial to the WARFASA trial, the ASPIRE trial, looked at the role of aspirin after patients with VTE’s had completed at least 6 weeks of full anticoagulation and was recently published in the NEJM.

The ASPIRE trial is a multicentre, randomised double blind study. Patients were randomised into two groups, either to 100mg aspirin daily or placebo. The primary efficacy endpoint was symptomatic recurrent VTE (DVT or PE) and the primary safety endpoint: major or clinically relevant non-major bleeding

The results:

• There was no difference in the primary endpoint (recurrent VTE) between aspirin and placebo (14% vs. 18%, HR 0.52 to 1.05, p=0.09)
• The main secondary endpoint – major vascular events – was improved with aspirin (5.2% per year vs. 8% per year, p=0.01, NNT 35)

The author’s conclusion:

…the findings of the ASPIRE study, especially when considered together with data from the WARFASA study, provide consistent evidence that low-dose aspirin is beneficial in preventing recurrent venous thromboembolism and major vascular events in patients who have had a first episode of unprovoked venous thromboembolism. Thus, aspirin is an attractive option for such patients once they have completed an initial course of anticoagulation therapy.

However this study is not without its problems. Reading just the abstract never tells you the whole story and therefore I would encourage you all to read the full paper before the discussion this Sunday at 8pm. A link to the free full text can be found at the excellent NEJM Physicians Now blog

Apologies for the change of paper. I do hope to look at the CHEST study soon but I am desperately trying to only use open access papers for the journal club to make it as inclusive as possible.

After a break #twitjc is coming back very soon…..

Tomorrow the details of our return will be announced.

In the meantime I need your help. I would love to have some feedback on the journal club and how we could improve it. If you could take a moment to answer the four questions below I would be incredibly grateful.

1. How often do you participate in a traditional journal club and if so how is this run and who joins in?

2. What are the benefits of participating in twitter journal club?

3. What improvements could we make to the running of the journal club?

4. Would you recommend twitter journal club as a valid form of CBD to a colleague?

Any other feedback outside the scope of these questions would be fantastic, thank you all in advance

1. Is the methodology of this study appropriate to answer the clinical question?

2. Were the outcomes, both primary and secondary, clinically relevant?

3. Does the lack of a placebo in the control group undermine the results of this study?

4. Do the benefits of administering glargine in this group outweigh the risks?

This week’s summary is written by the fantastic @paedssho, thank you to him for taking some of my workload away from me (actually more like wrestling it off me, I admit to being a bit of control freak).

It is well-established that an elevated fasting plasma glucose level is an independent risk factor for adverse cardiovascular outcomes. Basal insulin secretion is required to maintain normal fasting plasma glucose levels; an elevated fasting plasma glucose level indicates that there is insufficient insulin secretion to overcome underlying insulin resistance. The correction of this deficiency may reduce adverse cardiovascular outcomes.

Such a possibility has not been formally tested; however, large outcomes trials of more versus less intense glucose lowering in which insulin was used in both study groups have not shown a clear cardiovascular benefit.  In addition, one trial showed increased mortality.  Conversely, extended follow-up of the trial with the biggest between-group difference in insulin use until now (the United Kingdom Prospective Diabetes Study [UKPDS]) revealed a 15% reduction in myocardial infarction and a 13% reduction in death among people with new-onset type 2 diabetes.

The UKPDS findings suggest that early provision of sufficient basal insulin to normalize fasting plasma glucose levels may safely reduce incident cardiovascular outcomes. Evidence that exogenous insulin may slow the decline in pancreatic function with time suggests that such an intervention may also reduce incident diabetes in people at risk for the disease. These hypotheses were tested in the present study, the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, which involved people 50 years of age or older with impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes in addition to other cardiovascular risk factors.

The multi-centre international randomised trial, with over 12,000 patients from 40 countries, compared the effect of:

1. titrated basal insulin glargine, against
2. standard care

on cardiovascular outcomes.There were two co-primary outcomes; the first was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, and the second was a composite of any of these events, a revascularisation procedure, or hospitalisation for heart failure.

Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first co-primary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27).

New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years.

The author’s conclusion:

 When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight.

The paper, “Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia” (NEJM 2012; 367:319-328, July 26 2012) can be found open access via the ever-brilliant Now@NEJM blog

http://blogs.nejm.org/now/index.php/insulin-and-cardiovascular-outcomes-in-dysglycemia/2012/07/27/

The paper will be discussed at 8.00pm 19th August.  Please join in; it should help to plug the Olympic-shaped gap in your weekend.