Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04876742 |
| Other study ID # |
BASEC 2022-00779 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
January 18, 2023 |
| Est. completion date |
December 31, 2024 |
Study information
| Verified date |
August 2023 |
| Source |
University Hospital, Basel, Switzerland |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigators hypothesise that the daily administration of 0.5L alcohol-containing wheat
beer at 8 pm over a study period of 6 days in a row leads to a lower prevalence of delirium
compared to water following the same administration scheme.
Description:
Delirium
Delirium is a complex state of confusion that can be seen as an acute failure of brain
function. It is characterised by fluctuating deficits in cognition and attention,
dysregulation of emotions and circadian rhythm as well as psychomotor changes.
In intensive care units (ICU) delirium is the most frequent syndromic complication with a
prevalence between 26 - 60%. In mechanically ventilated patients, delirium is even detected
in more than 80%. In elective cardiac surgery patients admitted to the ICU for postoperative
monitoring postoperative delirium presents as a major complication and occurs in up to 33.5%.
Hypoactive delirium outperforms the other two types - hyperactive and mixed - by far.
Occurrence of delirium is associated with several negative repercussions: Delirious patients
show higher prevalence in morbidity and mortality, longer stays in intensive care units and
the regular ward, as well as impaired cognitive function even months after the acute illness.
The intensity of impairment in cognitive and executive function correlates with the duration
of delirium. Furthermore, delirious patients cause major additional costs of up to 20% more
compared to non-delirious patients.
Although there are several approaches for prevention of deliria in ICUs they are still highly
prevalent causing a high and versatile burden as mentioned above. The several mainly
pharmacological treatment approaches are more to be seen as a symptomatic treatment than a
causal treatment. No groundbreaking prevention or treatment strategy has been found so far.
Therefore, improvement of existing and development of new prevention strategies is therefore
crucial and highly necessary. Further it has to be shown if prevention of delirium has an
effect on clinical outcome.
Between March 2018 and February 2019, 584 patients that met the inclusion criteria of this
study were admitted to the ICU of the University Hospital Basel. Of those, 167 patients
(28.6%) developed a delirium within the first 48 hours. After 7 days (168 hours), 277 (47%)
had at least once an ICDSC score of ≥4.
Wheat beer
Consumption of alcoholic beverages and therewith beer is widespread in Switzerland. Healthy
effects of moderate beer consumption, especially benefits for prevention of cardiovascular
diseases, are discussed in literature. Beer's major ingredients are water, hop, malt and
yeast.
Alcohol Surveys in US American ICUs showed a pre-existing alcohol use disorder in 16-31% of
ICU patients. Further research showed anamnestic alcohol abuse as a significant risk factor
for development of delirium in ICUs.
Swiss governmental statistics show a widespread alcohol consumption among the Swiss
population: While 82% consume alcohol periodically, 10% drink alcoholic beverages on a daily
and almost 60% at least on a weekly basis. Alcohol consumption increases with age. In the
group of the over 75-year-olds around 40% drink alcohol daily. Around 5% of the population
bear a chronic risky alcohol consumption, 16% get drunk at least once a month. Thereby beer
is one of the most popular beverages.
Alcohol, in alcoholic beverages ethanol, targets multiple central receptors and neural
networks. In habituated individuals an abrupt abstinence from alcohol consumption leads to
generalised central hyperexcitability due to unchecked excitation and impaired inhibition
whereby alcohol withdrawal syndrome (AWS) and delirium tremens (DT) are more likely to occur.
Similar mechanisms can be thought of in patients with moderate, non-abusive alcohol
consumption favouring or causing delirium.
Hop Hop (Humulus lupulus) is a major ingredient of beer. Its main pharmacologically active
constituent is humulone. It bears several health beneficial properties. Its main impact is
the calming effect, which could be shown in a study in healthy nurses when consuming
alcohol-free beer. Improvement of sleep quality and a hypnagogic effect induced by
alcohol-free beer and hop extracts could also be shown in different studies.
On the molecular level the hop's sedating and hypnotic effect could be shown at the
gamma-aminobutyric acid A (GABAA) receptor in a rat model which - positively modulated by
ethanol - shortened sleep onset, increased duration of sleep and decreased the spontaneous
locomotion.
Standard procedure and treatment of delirium at University Hospital Basel (USB)
All patients admitted to the ICU receive a standard care prevention for delirium including
management of causes of delirium such as pain treatment using non-opioid and opioid
analgesics and support of sleep-wake-cycle using Melatonin (Circadin®). The support in
perception, orientation and communication as well as early and regular mobilisation, general
stress reduction and inclusion of patient's next of kin are the main pillars of standard
delirium care prevention.
For assessment of delirium Richmond Agitation Sedation Scale (RASS) and the Intensive Care
Delirium Screening Checklist (ICDSC) are used regularly for delirium recognition (see
"Measurement of delirium and sedation" in section 3.2 for details).
Current standard prevention and treatment of non-withdrawal delirium in the intensive care
unit of the University Hospital Basel depends on the type of delirium.
Hyperactive and mixed delirium (ICDSC ≥ 4, RASS > 0) is treated when RASS ≥ 2 with Quetiapin
(Seroquel®) orally or Haloperidol (Haldol®) intravenously if oral administration is not
possible. As rescue for excessive motoric restlessness Levomepromazin-neuraxpharm intravenous
or intramuscular is used. If restlessness with RASS ≥ 2 is persistent, syringe pumps with
Dexmedetomidine (Dexdor®) or Propofol (Propofol®) are installed.
For treatment of hypoactive delirium, caring measures including registering and rapid
handling of hunger, thirst, urine or stool urging are of great importance. Further preventive
measures of delirium in general are applied for treatment such as giving orientation and
feeling of safety, support of perception, activation and mobilisation.
For withdrawal delirium a separate treatment algorithm is provided. According to the intern
treatment concept withdrawal delirium presents usually as hyperactive delirium with agitation
tremor, tachycardia, sweating and hallucination in combination. For the prevention and
treatment the same non-pharmacological procedures as described above for other types of
deliria are applied.
Pharmacologically Lorazepam (Temesta®) or Phenobarbital is administered in case of motoric
agitation. In case of conducting oneself in an endangering way for the patient itself or
others a Propofol perfusor might be installed. Additionally, Clonidine (Catapressan®) is
administered when strong vegetative symptoms occur. As a rescue treatment for most intense
motoric agitation Levomepromazin-neuraxpharm is administered. For concomitant psychosis
Haloperidol (Haldol®) is foreseen for its treatment. Alongside an early start of nutritional
therapy as well as substitution of vitamins and minerals are important.
Research question
The BABE-D clinical trial wants to provide answers to the question if delirium in critically
ill patients can be prevented or reduced in duration, as well as if intensity of agitation
can be reduced by regularly administering a moderate amount of beer.
