Contact information
Type
Scientific
Primary contact
Dr Ivan Zuran
ORCID ID
Contact details
General Hospital Celje
Department of Angiology
Endocrinology
and Rheumatology
Celje
3000
Slovenia
+386 (0)3 423 3479
ivan.zuran@yahoo.com
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Intensive insulin treatment in critically ill patients and forearm blood flow: a randomised parallel group trial
Acronym
Study hypothesis
Intensive treatment of critically ill patients with insulin to the range of serum glucose concentrations between 4.4 mmol/l and 6.1 mmol/l decreased the mortality rate in the group of patients treated at the department of intensive care following an operative procedure, while in medical patients such treatment had a favourable effect on the occurrence and degree of vital organ failures and the length of artificial ventilation. The mechanisms of insulins positive effects are not clear. The purpose of this research was to test the hypothesis that positive effect of intensive insulin treatment are related to blood flow in different organs including the forearm in artificially ventilated septic patients.
Ethics approval
Ethical Committee at the Ministry of Health of Republic of Slovenia approved on the 14th May 2002 (ref: 88/05/02)
Study design
Single centre interventional parallel group randomised trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Mechanical ventilation due to acute respiratory failure
Intervention
Patients were randomised into two groups as regards the regulation of blood glucose: intensive (Group 1) and standard (Group 2). In the standard protocol the serum glucose concentration was maintained within the range of 7.0 - 11.0 mmol/l while in the intensive protocol the concentration was maintained within the range of 4.4 - 6.1 mmol/l.
In a 50 ml syringe, 50 IE of human insulin for intravenous administration was diluted in a 0.9% solution of sodium chloride. The amount of infusion was adjusted according to the values of serum glucose concentrations according to a study published by Brown and Dodek (2001). The serum glucose concentration was determined with the hexokinase method hourly at the beginning of insulin treatment and every 2 hours thereafter, except when the dose of insulin was adjusted. In this case, the next measurement was taken after 1 hour.
The treatment was initiated within 48 hours from the start of artificial ventilation. Up to that point, the serum glucose concentrations were maintained in the 8.8 - 11.0 mmol/l range by means of subcutaneous administration of rapid-acting insulin or the above described infusion. Blood glucose levels were maintained according to different protocols for 72 hours from the start of the trial.
Intervention type
Drug
Phase
Not Applicable
Drug names
Insulin
Primary outcome measure
1. Measurements of forearm flow, performed by means of a plethysmograph (model EC5R, D.E. Hokanson, Inc., USA). In brief outline: the patient was in a supine position with the upper body lifted by approximately 150 cm. The forearm was positioned in the level of the right atrium (at 3/5 chest height). A 10 cm wide cuff was placed on the forearm and connected to the rapid cuff inflator. A mercury-filled clamp with a circumference 1.5 - 2 cm smaller than the forearm circumference was placed on the widest part of the forearm. A second, 8 cm wide cuff was placed just above the wrist in order to block arterial inflow to the thermoregulatory area, in our case the hand. The upper arm cuff pressure was preset to 50 mmHg. After 10 seconds of inflation the cuff was deflated for 5 seconds. Prior to the measurement, the wrist cuff was inflated to the value 40 mmHg above the systolic pressure for the duration of a single measurement (approximately 1 minute). The plethysmographic curve was recorded and measurement was repeated every 10 minutes, and each individual measurement lasted 1 hour.
2. Instantaneous arterial flow, calculated manually by analysing the average value of three plethysmographic recordings
3. Values of instantaneous arterial flow, expressed as ml/100 ml of tissue/min. To estimate the total forearm flow the area under the 60-minute arterial flow curve was calculated. All arterial flow measurements were taken at the beginning of the study (t0), after 2 hours (t1), after 24 hours (t2) and after 72 hours (t3) between 8 am and 9 am, with the exception of insulin infusion measurements, which were taken between 11 am and 12 pm.
Secondary outcome measures
1. Duration of mechanical ventilation (days)
2. 30-day mortality rate
Overall trial start date
01/01/2005
Overall trial end date
31/12/2006
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
Critically ill mechanically ventilated patients of both sexes, aged 18 years and older, who meet following criteria:
1. Admission criteria for sepsis (at least two American College of Chest Physicians/Society of Critical Care Medicine [ACCP/SCCM] 1992 criteria)
2. Mechanical ventilation due to acute respiratory failure
3. No prior data of diabetes mellitus
4. Start of the trial up to 48 hours after admission
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30 patients in both groups
Participant exclusion criteria
1. Aged below 18 years
2. Pregnancy
3. Terminal neoplastic disease
4. Known diabetes mellitus
5. Mechanical ventilation due to due to primary failure of respiratory muscles
6. Mechanical ventilation due to brain injury
Recruitment start date
01/01/2005
Recruitment end date
31/12/2006
Locations
Countries of recruitment
Slovenia
Trial participating centre
General Hospital Celje
Celje
3000
Slovenia
Funders
Funder type
Hospital/treatment centre
Funder name
General Hospital Celje (Slovenia) - Department for Education and Research
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20003200
Publication citations
-
Results
Žuran I, Poredos P, Skale R, Voga G, Gabrscek L, Pareznik R, Intensive insulin treatment improves forearm blood flow in critically ill patients: a randomized parallel design clinical trial., Crit Care, 2009, 13, 6, R198, doi: 10.1186/cc8202.