Landmark NZ Study Suggests Increased Death Risk From Common Intensive Care Drug

A New Zealand-led trial, the largest ever undertaken in critically ill patients, shows that one of the world’s most commonly prescribed medicines is potentially risking the lives of thousands of the sickest patients in hospitals across the globe each year.

“The findings from this trial could save the lives of hundreds of New Zealand patients and tens of thousands of patients in hospital intensive care units worldwide each year, and for essentially zero cost” says study lead author and Wellington Hospital intensive care specialist Dr Paul Young from the Medical Research Institute of New Zealand (MRINZ).

When patients are sick enough to require treatment in a hospital intensive care unit (ICU), many are put on medicines to prevent bleeding from stomach ulcers. For decades, intensive care doctors have prescribed one of two types of ulcer-preventing medicines: proton pump inhibitors (PPIs) such as Losec (the trade name for omeprazole) *, or histamine-2 receptor blockers (H2RBs) such as Zantac (the trade name for ranitidine) *. PPIs are among the most commonly prescribed medicines in the world.

The PEPTIC study, just published in the prestigious Journal of the American Medical Association (JAMA), compared the risk of death with these different types of ulcer-preventing medicines when used on patients in the ICU. It found that while PPIs are slightly better at preventing bleeding from ulcers, they might actually lead to more deaths overall.

“The results showed that for every 1000 ICU patients treated with a PPI medicine, five fewer will have a major bleed from a stomach ulcer compared to when an H2RB medicine is used” says Dr Young. “However, the possibility that this small reduction in bleeding risk with the use of PPI medicines might come at the expense of a greater risk of death is of real concern. In particular, in this study, we showed that the risk of death was significantly higher with PPIs in patients admitted to the ICU after heart surgery and in those most gravely ill. The best estimate we have is that avoiding using PPIs to prevent ulcers in ICU patients will prevent 200 deaths in New Zealand ICUs per year and tens of thousands of deaths internationally. We don’t know for certain how PPIs might increase the risk of death but suspect it relates to these medicines affecting the immune system”.

The landmark three-year study, the largest ever randomised clinical trial ever undertaken in critically ill patients internationally, included almost 27,000 patients from 50 ICUs in 5 countries; New Zealand, Australia, the UK, Ireland and Canada. The Health Research Council of New Zealand-backed trial involved patients from 7 New Zealand hospital ICUs; Auckland City, North Shore, Middlemore, Waikato, Tauranga, Wellington and Nelson. Nearly two-thirds (18,000) of the total 27,000 patients came from Australia and New Zealand.

Dr Young says the results of this trial are already making waves internationally.

“The impact of this study is already substantial” he says. “Initial indications are that the majority of intensive care specialists will stop using PPIs routinely to prevent ulcers in ICU patients. Both PPIs and H2RBs are established medicines with similar costs and this study is a great example of how, when comparing the effectiveness of treatments we’ve used for a long time like this, you never know what you’re going to find”.

Auckland City Hospital Intensive Care specialist Dr Colin McArthur agrees the results have wide-reaching implications.

"This very large study of a common ICU treatment is likely to change the approach to critically ill patients at risk of bleeding from ulcers in ICUs around the world" says Dr McArthur.

“The study highlights the impact that New Zealand’s talented pool of clinical researchers can have on healthcare at both national and international level” says Health Research Council acting Chief Executive Dr Vernon Choy. “It’s a good example of research providing robust information about clinical treatment that can lead to changes in everyday practice”.

Notes for Journalists:

• *This trial relates to the use of omeprazole (Losec) on critically ill patients in intensive care units. There is no suggestion that omeprazole, one of the most commonly prescribed medicines in the world, is unsafe in any way for general patient use in the community. Patients on omeprazole should not stop taking it without consulting their GP.
• Medsafe issued an alert to medical professionals in December stating that ranitidine is now in limited supply due to concerns it may contain impurities in its manufacture which, due to exposure over a very long period of time, may carry a very small cancer risk. Other medicines from the H2RB class are available.

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