Dopexamine & Meta-analysis

Meta-analyses of the effects of dopexamine in major surgery: do all roads lead to Rome? J. J. Pandit. Anaesthesia. 64;6:585-8. (Editorial)

Meta-analyses of the effect of dopexamine on hospital mortality. Gopal et al. Anaesthesia. 64;6:589-94.

Effect of dopexamine infusion on mortality following major surgery: individual patient data multi-regression analysis of published clinical trials. Crit Care Med. 2008 Apr;36(4):1323-9

Two recent meta-analysis have been published in answer to the question “does dopexamine reduce mortality in high risk general surgical patients”, with conflicting results. Pearse’s group found no difference in mortality using the entire data set, but a 50% mortality reduction with low-dose infusions. Gopal’s group found no difference using essentially the same data set, but a different statistical methodology. Panjit’s accompanying editorial does an excellent job of dissecting out why such apparent large differences might arise from the same data, and is recommended.

The take home message for me is that the results of combining heterogeneous studies together into meta-analysis tell us more about the statistical method than they do about the clinical question. Does dopexamine have a role? Is it the dopamine renal failure story all over again? I’m afraid we’ll need more data…..

Management of Subarachnoid Heamorrhage

Management of aneurysmal subarachnoid heamorrhage. Dringer. M. Critical Care Medicine 37 (2) Feb 2009; 432-440.

A useful & comprehensive educational review article from CCM on the management of SAH, highlighted for interest. Unfortunately for copyright reasons we can’t provide a link to the pdf, but you can access it from the above link if you have an ATHENS account.

Weaning & Extubation Protocols in Neuro ICU

Rate of Re-intubation in mechanically ventilated patient neurosurgical patients : An evaluation of a systematic approach to weaning & extubation. Navalesi, P et al. Critical Care Medicine 2008 (36) 11.

This article was recently presented at QMC’s ICM journal club, who have kindly offered their presentation for inclusion on Critical Insight. You can find it in the blue box on the right, named “QMC Neuro Extubation CCM 2008″.  If your journal club would also like to submit presentations please see the “how to post” page for more info.

Use of Polyclonal Ig as Adjuvant Therapy for Sepsis/Severe Sepsis K Georg. Kreymann et al CCM 2007 35(12) 2677-

This important paper is a meta analysis of all trials including the use of IVIG in patients (adult and Children-including neonates) with sepsis and severe sepsis. IVIG bind up toxins, allow oponisation and bind toxins and superantigens Previous papers from the Cochrane group have apparently not included all studies which this meta analysis has tried to do.
The search criteria was vigorous, including peer reviewed articles as well as personal communications, letters etc. They particularly included studies which used mortality as an end point. They graded papers on strict guidelines as there was a paucity of double blinded randomised placebo controlled trials (DBRPCT) to try and add some power to the meta analysis.

In all 27 trials were included. In 15 trials, including 1492 patients (adults and children) showed the use of IVIG created a RR of 0.79 (significant). When split into type of IVIG, the IVIGAM (immunoglobulins containing predominantly IVIG A and M) were used in 560 patients with a significant RR of 0.66. With just IVIG, including 932 patients, RR was 0.85 (significant). IVIG A and M showed further benefit over just IVIG. It is interesting to note many studies showed a positive trend but these trials were rated as significantly heterogeneous on tests. The largest trial showed no difference between those treated with IVIG and these not. 12 trials included neonates and are not discussed further here.

Multicentre RCTs evaluating mortality in ICU – Doomed to fail?

Multicentre RCTs evaluating mortality in Intensive Care : Doomed to Fail ? Gustavo A. et al. Crit Care Med, 2008, vol 34, no 4.

The authors performed a systematic search for multicentre RCTs in adult ICU targetting mortality as a primary outcome measure. Perhaps surprisingly they found only 72. Of these, 10 reported a positive effect, 7 negative and 55 neutral.

The authors make some interesting points…

• of the 10 positive results not all have been implemented, either because of tight inclusion criteria or subsequent neutral/ negative evidence
• 30% of studies failed to adequately report a power calculation
• assuming a commonly targeted mortality benefit (10%), they estimate approx 60% of studies would be underpowered at the 90% confidence limit.

So is mortality as unrealistic endpoint in disease states inadequately differentiated (like ARDS or sepsis) ?