Leiden University: Improving painkiller dosing in the clinic

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Children, cardiac surgery patients or people who are obese. How can we improve the dosing of painkillers for these patients? Hospital pharmacist Sjoerd de Hoogd of the St. Antonius Hospital in Utrecht investigated this. He combined data from the hospital with the knowledge and expertise of the Leiden Academic Centre for Drug Research (LACDR). De Hoogd received the PhD thesis award from the Dutch Association of Hospital Pharmacists.

‘Pain and pain management are getting more and more attention in the hospital,’ says De Hoogd. ‘It is an quality indicator, also for the inspectorate. I focused on pain management during and after surgery. The number of operations is increasing, and there are many different patients. For many of them, we don’t yet know exactly how to dose painkillers best. So we looked at how to optimise the dosage, duration and type of painkillers for some specific patient groups.’


Sjoerd de Hoogd after the awarding of the PhD Thesis Award

Collecting data in the hospital
De Hoogd and his colleagues studied three types of patients: adults who underwent cardiac surgery, children who underwent heart surgery and morbidly obese patients after gastric bypass surgery. At the St. Antonius Hospital, the researchers collected data such as pain scores, the time at which medication was administered, and the dosage and concentration of painkillers in the blood at different times. They also looked at whether pain was still present a year after the heart surgery. ‘In children, the focus was on when and how often a so-called “rescue event” was needed,’ De Hoogd says. ‘In other words, when nurses needed to administer an extra dose of pain relief.’

When is more pain relief needed?
With all that data, De Hoogd then proceeded his research at the LACDR. ‘We put all the data into a computer model. That way, we could compare the measurement data with the probability of a rescue event: experiencing pain. What influences that chance? What causes someone to be needing another dose of pain relief, and how can we improve their situation? Time, for example, has a logical influence: the more time has elapsed after surgery, the less chance there is of a rescue event.’

‘It doesn’t always help to give more morphine’’
‘It doesn’t always help to give more morphine’
In children, something special appeared to be going on. De Hoogd: ‘We had data from 35 children who were given morphine postoperatively after cardiac surgery according to standard protocol. In total, additional morphine was administered 130 times. However, this happened at both low and high concentrations of morphine in children. So we saw no clear relationship between morphine concentration and the effect on pain control.’ And that’s important for treatment. ‘It shows that giving an extra dose of morphine does not always help. We hypothesized that the appropriate receptors, the sites where morphine binds to, are already saturated. Or that morphine needs more time to excert its effect. In those cases, it would be more helpful to give another drug.’

‘Through this collaboration, Sjoerd has made the most of the data from the clinic.’

Clinic and statistics strengthen each other
This research is a great example of how the clinic and academy can strengthen each other, according to supervisor Catherijne Knibbe. ‘By combining clinical expertise with the statistics and models of the LACDR, Sjoerd has made the most of the available data. That has resulted in concrete results for different patient groups.’ De Hoogd agrees: ‘It is very valuable to learn how to process patient data in models. But also vice versa: Researchers from the LACDR have been able to watch real operations and the administration of painkillers in the hospital. We all benefit!’