Critical Illness
Conditions
Brief summary
A high blood lactate and a high peripheral to central temperature difference (deltaT) are associated with a higher mortality in critically ill patients. Both measures are signs of a reduced microcirculatory bloodflow or vasoconstriction and are associated with shock. It is unknown which medication can best be used to improve deltaT and lactate clearance. Ketanserin is being used in the intensive care setting for decades to optimize circulatory parameters. Ketanserin is a serotonin type 2-receptor blocker (5-HT2). Blocking the 5-HT2 receptor with ketanserin can attenuate pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation. As a consequence, the enhanced blood flow in the skin will increase the peripheral temperature and decrease deltaT. At the same time an increased flow in the microcirculation may lead to a reduction in lactate production. Objective: To determine the effects of a continuous ketanserin infusion on peripheral temperature and lactate clearance in critically ill patients with either a high lactate or a high deltaT.
Detailed description
Rationale: A high blood lactate and a high peripheral to central temperature difference (deltaT) are associated with a higher mortality in critically ill patients. Both measures are signs of a reduced microcirculatory bloodflow or vasoconstriction and are associated with shock. On the other hand, it has not been shown yet that interventions leading to improvement of this temperature gap reduces mortality or improves any other outcome measurement. Moreover, it is unknown which medication can best be used to improve deltaT and lactate clearance. Ketanserin is being used in the intensive care setting for decades to optimize circulatory parameters. Ketanserin is a serotonin type 2-receptor blocker (5-HT2). Blocking the 5-HT2 receptor with ketanserin can attenuate pathological vasoconstriction. In these ways ketanserin can reduce vasoconstriction and can improve the microcirculation. As a consequence, the enhanced blood flow in the skin will increase the peripheral temperature and decrease deltaT. At the same time an increased flow in the microcirculation may lead to a reduction in lactate production. Objective: To determine the effects of a continuous ketanserin infusion on peripheral temperature and lactate clearance in critically ill patients with either a high lactate or a high deltaT. Study design: A multicentre double blind randomized controlled trial. Study population: All adult intensive care patients above 17 years old with a deltaT of \>6°C with informed consent given by the patient or legal representative. Intervention (if applicable): The intervention is a continuous pump driven Ketanserin infusion of 0.75 ug/kg/min for eight hours. The control group will receive the same volume of glucose 5%. Main study parameters/endpoints: Change in DeltaT (measured per hour) Change in lactate (measured per 2 hours) Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The risks of ketanserin infusion are limited but can be a QTc prolongation and a slight decrease in blood pressure. The study needs an arterial blood sample on inclusion, and after 2, 4, 6 and 8 hours of 1.5 ml each. In addition, a 6 ml blood sample at T=4 and T=8 hours.
Interventions
DRUGKetanserin
The dose of 0.75 ug/kg/min is a dose that has been used frequently in critically ill patients. The concentration of the study drug infusion will be 40 mg/40 ml glucose 5%. The maximum dose however will be 4.5 mg per hour for patients with a weight more than 100 kg. The pre-filled 50 ml syringes will be filled with 40 ml of a solution containing 40 mg ketanserin or 0 mg ketanserin in glucose 5%. The minimum number of ketanserin vials (2 ml with 5 mg/ml) that are needed is 240 (40 mg = 4 vials per patient). Duration of intervention: 8 hours
OTHERPlacebo
Glucose 5% solution
Sponsors
Frisius Medisch Centrum
Onze Lieve Vrouwe Gasthuis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo medication
Intervention model description
Randomised controlled trial (blinded)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* DeltaTemperature greater that 6.0 °C. * Age 18 years or older * Admitted to the ICU for any reason * Signed informed consent from the patient or legal representative
Exclusion criteria
* Pregnancy * No possibility to obtain informed consent * QTc above 550 msec, * Arrhythmias, including bradycardia defined as a heart rate below 50/min; 2nd and 3rd degree AV block; ventricular tachycardia * Blood Potassium level \< 3.5 mmol/l * Blood Magnesium level \<0.5 mmol/l * Allergy for ketanserin * DeltaT less than 6°C. * Patients undergoing therapeutic hypothermia * Patients admitted after cardiac arrest * Patients admitted after cardiac surgery
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Delta Temperature | 8 hours (after start of the study medication) | Delta Temperature is calculated from the difference between central (rectal) and peripheral (forefoot) temperature |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lactate clearance | 8 hours (after start of the study medication | Lactate clearance is defined as :(Lactate (admission) - Lactate (8 hours))\*100 / Lactate (admission) (Lactate (admission) - Lactate (8 hours))\*100 / Lactate (admission) A lactate clearance of 10% or more is regarded as clinical relevant |
| hospital length of stay | 6 months after start of study medication | Length of stay hospital |
| mortality | 6 months after start of study medication | mortality at hospital discharge |
| ICU length of stay | 6 months after start of study medication | length of stay in the ICU |
| ICU mortality | 6 months after start of study medication | mortality at ICU discharge |
Outcome results
None listed