Archive for the ‘NEJM’ Tag

A Black Water Day ?

Mortality after Fluid Bolus in African Children with Severe Infection. Maitland, K et al. New England Journal of Medicine, May 26th 2011 (epub ahead of print) (DOI: 10.1056/NEJMe1105490)
An interesting paper published in this weeks NEJM will cause substantial comment and concern after it’s headline result showed increased mortality with rapid fluid resuscitation in paediatric sepsis. This surprising result is potentially extremely important as, if verified, undermines much of peadiatric (and adult)emergency care.

Before examining the paper in detail it’s worth making a few comments on what we think we know already….

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NMB in Early ARDS.

A fascinating study from the NEJM.

Neuromuscular Blockers in Early ARDS. Papazian, L et al. NEJM. Vol 6, 12, 2010.

This RCT gave a 48 hr infusion of cis-atricurium to early (<24hrs) ARDS patients. It is the first study to show a mortality difference in this condition since ARDSnet a decade ago (although caution is required as it was underpowered). Whilst it is likely that a large proportion of the population included in this study (early, severe ARDS) will already be on NMB to aid ventilation, there has up until now been an assumption that this therapy was a necessary harm (due to the risk of critical illness polyneuropathy and subsequent slow weaning). This study questions that wisdom, showing both a reduction in adjusted mortality at 90 days (although not at 28) and no increase in the risk of CIPN. The results need to be taken with caution, but are certainly interesting and if confirmed may offer an important advance. There is further detailed analysis of the paper in the presentation ‘Atricurium ARDS’ in the blue box. Remember that restrictions on comments have been lifted on Critical Insight, no sign in required – so let us know your opinions.

SOAP II – That’s cleaned that up then.

Dopamine has been the vasopressor of choice in septic patients in continental europe historically, although this may be changing. Dopamine has theoretically beneficial effects in maintaining splancnic and renal perfusion although in the SOAP trial (observational) suggested that there was an excess of mortality of dopamine treated patients. The old story of “renal dose dopamine” having an additional effect over and above the improvement in perfusing pressure has been discredited, but this result suggests a harmful signal over and above noradrenaline (the preferred agent in the UK).

Comparison of dopamine and norepinephrine in the treatment of shock. De Backer DN, et al. N Engl J Med. 2010 Mar 4;362(9):779-89.
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Renal Intensity – How High ?

The ANZICS group appear to have done it again; that is taken a single centre trial done in Europe, repeated it in a sensible and pragmatic way but in a much larger, adequately powered multi centre setting and determined an evidence based outcome. It’s something of a shame that again the evidence based outcome doesn’t support the optimism of the initial trial.
This time the therapy in question is the ‘dose’ of RRT (renal replacement therapy). A previous trial by influential group led by Ronco suggested a survival benefit of 35mls/kg/hr effluent flow rate as opposed to 20ml/kg/hr. A major US study (the Veterans/NIH study) showed no difference in mortality but was limited in its application is the UK because of the relatively large proportion of patients who received intermittent heamodialysis, and the slightly complicated rationale for choosing which patients received which therapy. Most UK ICUs would provide only CVVH (or variants) to ICU patients.
Intensity of Renal Replacement Therapy in Critically Ill Patients. RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S.   N Engl J Med.   2009 Oct 22;361(17):1627-3.

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Organ donation after Cardiac death

Pediatric Heart Transplantation after Declaration of Cardiocirculatory Death. Bouchek, M et al. New England Journal of Medicine. 2008: Volume 359:709-714.

A report in the NEJM describes a paediatric non-heart beating donor programme for cardiac transplants. This has not been done previously as the ischemic time between cessation of cardiac output and declaration of death has thought to be too great. The program shortened this time to 1.25 mins, justified as being longer than the 60 seconds maximum reported time for auto-resuscitation. Arterial cannulae were placed prior to death to allow rapid infusion of heparin and cooling solutions. There are 3 editorials to accompany the article debating the ethical questions that the program raises. Bernat and Veatch argue that the program makes explicit the conflict within non-heart beating donation, i.e. it may require either additional treatment of the donor, or require a change the definition of death. Continue reading

Intensity of Renal Support. NIH ARF Trial Network. NEJM 2008.

Intensity of Renal Support in Critically Ill patients with Acute Kidney Injury. VA/NIH Acute Renal Failure Trial Network. N Engl J Med: May 20, 2008;359.

A copy of this paper is available as a PDF in the file box, or you can click the link above for full text.

Intro : This multicentre, non blinded RCT had 2 arms; High intensity intermittent HD (6/week) or CVVH at 35ml/kg vs low intensity intermittant HD (3/week) or CVVH at 20ml/kg. HD was used if the patient’s were heamodynamically stable (defined by cardiovascular SOFA score <2). 1124 patient’s randomised if ARF + 1 additional organ failure present (CRF excluded). Patients on low intensity treatment were permitted isolated ultra-filtration for volume overload if required . Primary end point was all cause mortality at 60 days.

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