Month of negative studies

Last 2 months have produced several negative studies in the field of critical care.

It is worthwhile to look at these studies altogether.

In the first study published in JAMA by Wittekamp BH, Plantinga NL, Cooper BS et el , the effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) was compared. 

Standard care was 2% chlorhexidine body washing and hand hygiene.  This was compared with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily.

Use of the above-mentioned aggressive oral and/ or GI Decontamination did not lead to reduction in resistant bloodstream infection in mechanically ventilated patients.

In the second study, published in NEJM by M. Krag, S. Marker, A. Perner et elcompared pantoprazole with placebo  in critically ill patients.

This was a multicenter European trial in which 3298 adult patients were randomly assigned to receive daily,
single-bolus, intravenous pantoprazole (40 mg) or placebo during their nonelective ICU stay. The patient population was at high risk for clinically important gastrointestinal bleeding.

There was no significant difference between the pantoprazole group and the placebo group in the rate of the primary outcome of death by 90 days after randomization (31.1% and 30.4%, respectively). This finding is similar to the mortality rates found in previous trials.

Similarly, no difference was found with regard to the secondary  outcomes of clinically important gastrointestinal bleeding, new-onset pneumonia, C. difficile infection, or acute myocardial ischemia.

HOWEVER, clinically important gastrointestinal bleeding occurred in 2.5% of the patients in the pantoprazole
group and in 4.2% of the patients in the placebo group. These results highlight the low prevalence of upper gastrointestinal bleeding in modern ICUs.

In the third study,  which is relevant to critical care, Brandon R. Hood,  Mark E. Cowen,  Huiyong T. Zheng et el Baby aspirin to that anticoagulants in preventing VTE in patients undergoing total knee replacement.

It was a large study of 41537 patients who underwent primary TKA.  The method of pharmacologic prophylaxis: neither aspirin nor anticoagulants for 668 patients (1.6%), aspirin only for 12 831 patients (30.9%), anticoagulant only (eg, low-molecular-weight heparin, warfarin, and Xa inhibitors) for 22 620 patients (54.5%), and both aspirin/anticoagulant for 5418 patients (13.0%). All patient used pneumatic Compression stockings.

A VTE event occurred in 573 of 41 537 patients (1.38%); 32 of 668 (4.79%) who received no pharmacologic prophylaxis, 149 of 12 831 (1.16%) treated with aspirin alone, 321 of 22 620 (1.42%) with anticoagulation alone, and 71 of 5418 (1.31%) prescribed both aspirin and anticoagulation. Aspirin only was noninferior for the composite VTE outcome compared with those receiving other chemoprophylaxis.

Total knee replacement has been historically considered high risk factor for VTE. If aspirin is as good as other anticoagulants in these patients, we should have a randomized trial and critically ill patients as well.

In another negative study, D. James Cooper, Alistair D. Nichol,  Michael Bailey et el compared effect of early sustained prophylactic hypothermia on neurologic outcomes among patients with severe traumatic brain injury.

This trial showed that early hypothermia did not improve long-term favorable functional outcomes (defined as a score of 5-8 on the Glasgow Outcome Scale–Extended at 6 months) in patientswith moderate and severe TBI.

In another negative study, Peter Pickkers,  Ravindra L. Mehta, Patrick T. Murray et el compared Human Recombinant Alkaline Phosphatase with placebo on creatinine clearance in critically ill patients. Alkaline phosphatase is an endogenous enzyme that exerts detoxifying effects through dephosphorylation of various compounds, including bacterial endotoxins. In animal models, it showed improved creatinine clearance.  However, this study showed that it does not have clinically significant affect in human beings. 

In the last study, Michael D. April,  Allyson Arana, Daniel J. Pallin et el  compared Intubation Success With Succinylcholine Versus Rocuronium in the emergency department. There was no difference in the first pass success rate vs any  complications.

These negative studies do help us choose rational treatment for out critically ill patients.




Pantoprazole reduces GI bleeding in intubated patients without improving mortality.Read more