This prospective study was approved by the regional ethics committee Karolinska Institutet (dnr 02–123), and complies with the principles laid down in the Declaration of Helsinki. The ClinicalTrials.gov identifier is NCT02753010. Informed consent was given after the patient had received written and oral information.
Patient characteristics
Ten patients, 77–97 years old (median 87), randomly recruited among those admitted with an acute hip fracture to Danderyd Hospital, Stockholm, Sweden, were recruited during a period of 12 months. Inclusion criteria were: female gender, age 75 years or above, and hip fracture within 24 h of admission. Exclusion criteria were: gastro-esophageal reflux disease, peptic ulcer disease, gastrointestinal motility disorder, pulmonary or cardiac disease, pharmacological treatment with motility-stimulating agents such as dopamine receptor blockers or macrolides, as well as previous long-term opioids or acid inhibitory agents, or cognitive impairment at the discretion of the investigator. Three patients did not have any previous disease or medication. Two suffered from diabetes mellitus, one substituted with insulin, the other under treatment with oral anti-diabetic drugs (glibenclamide). Two patients suffered from hypothyroidism, which was substituted with thyroxine. One patient had a history of stroke but was freely ambulant.
The study was conducted in the morning hours during fasting before surgery. Of the included nine patients, two were given morphine intravenously in the morning immediately prior to intervention (i.e. intake of beverage). During the intervention, starting 180 min prior to surgery, the patients had infusions with 5% glucose, and for diabetics 10% glucose 100 mL/h with insulin added to maintain blood sugar below 10 mmol/L. All patients underwent surgery under spinal anaesthesia according to routines. No adverse events were observed peri-operatively. The results were compared with two reference groups of 20 gender-matched subjects. One group consisted of 10 female patients (age 45–71) on the waiting list for elective hip replacement surgery due to osteoarthritis [
15]. The other group consisted of healthy female volunteers (age 28–55). All participants in the three groups were non-smokers and had normal body mass index.
Two-hundred mL of an iso-osmolar carbohydrate-rich drink (50 kcal, 12.6% carbohydrates per 100 mL, pH 5.0, Nutricia Preop; Numico; Zoetermeer, The Netherlands), was first given. Then, 1.5 g of paracetamol dissolved in 100 mL water was taken and thereafter another 200 mL of the carbohydrate-rich drink resulting in a total volume of 500 mL. This beverage has been approved by the Swedish Medicines Agency for use close to surgery.
In the two reference groups, the beverage was given to the patients in an upright sitting position. In the experimental group, due to the fracture-related pain, a half-supine position was allowed. If needed, additional intravenous morphine was allowed according to usual routines. Vomiting and nausea were registered.
Gastric emptying rate was assessed by the paracetamol absorption technique: after oral ingestion, the absorption of paracetamol is used as an indirect measure of the rate of gastric emptying. Using blood samples, plasma was obtained for measurement of paracetamol concentration at 0, 15, 30, 60, 120 and 180 min after the total intake of beverage and paracetamol solution.
The paracetamol absorption technique has been described and validated earlier, and shown to correlate well with other methods of measuring gastric emptying [
16‐
18]. The method was adapted from that described by Näslund et al. [
18], and the concentration of paracetamol (acetaminophen) was measured by HPLC (Sigma-Aldrich, St. Louis, MO; standard UC448) with a coefficient of variation of 5%. A statistical limit for significance was set at 5%.
Data analysis
Gastric emptying was compared between the groups using the lag phase, half-emptying time and complete emptying. The lag phase was defined as emptying of 2% of gastric contents, whereas gastric half-emptying time (T50) was defined as the period from the end of beverage intake with paracetamol until 50% of gastric emptying was achieved, and complete emptying as the time point when no more absorption of paracetamol occurred [
17]. The gastric emptying profile was estimated after conversion of plasma paracetamol concentration values to cumulated values, i.e. total absorption of the drug. In this way we obtained a gastric emptying curve from 0% to 100% adapted to a third-order polynomial. The sample size
n = 10 was calculated based on a ±20% minimum detectable effect and a statistical significance of 95%. For statistical evaluation of differences between the groups, the Kruskal-Wallis test with Dunn’s post hoc test was used. Results are given as medians with minimum and maximum values as well as means with the 95% confidence interval within parenthesis.