Condition category
Date applied
Date assigned
Last edited
Retrospectively registered
Overall trial status
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information



Primary contact

Dr Ivan Zuran


Contact details

General Hospital Celje
Department of Angiology
and Rheumatology
+386 (0)3 423 3479

Additional identifiers

EudraCT number number

Protocol/serial number


Study information

Scientific title

Intensive insulin treatment in critically ill patients and forearm blood flow: a randomised parallel group trial


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 insulin’s 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


Secondary study design

Randomised controlled trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Mechanical ventilation due to acute respiratory failure


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



Not Applicable

Drug names


Primary outcome measures

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


Overall trial end date


Reason abandoned


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


Age group




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


Recruitment end date



Countries of recruitment


Trial participating centre

General Hospital Celje

Sponsor information


General Hospital Celje (Slovenia)

Sponsor details

Oblakova 5

Sponsor type

Hospital/treatment centre



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


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

Results - basic reporting

Publication summary

2010 results in

Publication citations

  1. 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.

Additional files

Editorial Notes