Trial Information

IATROREF III: a Multifaceted Program for Improving Quality of Care in Critically Ill Patients

Design and methods Definition of adverse events

1. Error in insulin administration Insulin not given exactly as prescribed (including in
the written protocol used in the ICU). The error may be a planning error or an
implementation error regarding the nature of the insulin, dosage, preparation
modalities, or administration modalities. Insulin therapy requires monitoring of
capillary blood glucose levels.

2. Error in anticoagulant prescription Non respect of the recommendations about
indications, dosages, administration modalities, contraindications, drug-drug
interactions, and laboratory monitoring using the VIDAL (French Drug Compendium),
learned societies, ICU protocols, and local drug committees. Either unfractionated
heparin or low-molecular-weight heparin may be involved

3. Error in anticoagulant administration Anticoagulant not given exactly as prescribed.
The error may be a planning error or an implementation error regarding the nature of
the anticoagulant, dosage, preparation modalities, administration modalities, dosing
times, or dosing intervals. Either unfractionated heparin or low-molecular-weight
heparin may be involved.

4. Unplanned catheter removal Unplanned complete removal of a central venous catheter by
the patient or by staff while caring for the patient.

5. Unplanned extubation Extubation not planned by the physicians. Unplanned extubations
can be categorized as self-extubation by the patient, or accidental extubation for
technical reasons (porosity, section of the balloon, poorly secured tube), and during
patient care (bathing, taking radiographs, transportation, care).

Randomization procedure We will use a multicenter cluster randomized design to assess the
effectiveness of a multifaceted intervention. Our statistician will randomly assign each
unit to compliance with ICU guidelines as usual or implementation of the multifaceted
intervention to prevent one of the AEs. Randomization will occur at the ICU level. Units
that do not use the intervention program will serve as controls. The randomization procedure
will be repeated every 2 1/2 months for a total of four 21/2-month periods in 2007-2008.
During the month of January, the study will be prepared at each site, where a clinical
research assistant will be trained in the use of RheaTM data collection software
(http://outcomerea.org/rhea/install).

In the Iatroref II study, anticoagulant prescription or administration errors occurred in
59/1377 (about 6%) patients, insulin administration errors in more than 20% of patients, and
unplanned catheter or endotracheal tube removal in 4% of patients. For this study, we
collapsed unplanned catheter removal and unplanned extubation into a single group and
administration error and prescription error of anticiagulant in another single group.
Assuming that more than 2400 patients will be admitted to the four study ICUs during the
study period, the study would have greater than 80% power for detecting a 4% absolute
decrease in anticoagulant errors, a 3% absolute decrease in unplanned catheter or
endotracheal tube removal, and a 10% absolute decrease in insulin treatment errors. We will
use the two-sided score test for comparisons (Farrington and Manning). P levels ≤0.05 will
be considered statistically significant.

Interventions In each study ICU, a physician trained in clinical research and a a clinical
research assistant will prepare the study during the two weeks preceding randomization. The
intervention for each AEs will include three components: meeting with the ICU nurses and
physicians, distribution of educational materials including a pocket card showing the
recommendations about prevention of each AE, and quality improvement sessions twice a month.
At each site, the physician trained in clinical research and the clinical research assistant
will lead feedback meetings with the ICU staff every 2 weeks 1) to provide feedback about
AEs that occurred in the last 2 weeks, 2) to review compliance with recommendations on the
pocket card, and 3) to analyze the causes of AEs and suggest practice changes if
appropriate. A report on each meeting will be drafted.

Intervention for insulin administration errors

1. Meeting with the ICU staff to discuss the epidemiology of patients admitted with
diabetes mellitus outside the ICU, the pathophysiology of insulin resistance in ICU
patients, and clinical studies of glycemic control and mortality in wards and ICUs.

2. Pocket card showing how and why to control blood glucose and giving the guidelines for
controlling blood glucose levels with insulin infusions according to the protocol in
each study ICU.

3. Feedback meeting twice a month on insulin administration errors in the unit,
preventability, and appropriate changes in insulin treatment procedures.

Intervention for anticoagulant administration errors

1. Meeting with the ICU staff to discuss the pathophysiology of anticoagulants (heparin
and HBPM), indications, AEs, and specific problems in the ICU (e.g., use during
dialysis and in patients with renal failure).

2. Pocket card showing the nature of the anticoagulants, AEs, route of administration (IV
or enteral), specific problems in the ICU (e.g., use during dialysis and in patients
with renal failure).

3. Feedback meeting twice a month on anticoagulant administration errors in the unit,
causes of noncompliance with prescriptions, and preventability.

Intervention for anticoagulant prescription errors

1. Meeting with the ICU staff to discuss the pathophysiology of anticoagulants (heparin
and HBPM), indications, AEs, and specific problems in the ICU (e.g., use during
dialysis and in patients with renal failure).

2. Pocket cards with the nature of the anticoagulants, indications, dosage, route of
administration, and Aes, as recommended by the French Society for Anesthesiology in
2005 in a consensus conference.

3. Feedback meeting twice a month on anticoagulant prescription errors in the unit, causes
of noncompliance with recommendations, and preventability.

Intervention for unplanned extubation and catheter removal

1. Meeting with the ICU staff to discuss the epidemiology, risk factors, mortality, and
prevention of unplanned extubation and catheter

2. Pocket card showing methods for securing catheters and endotracheal tubes, the sedation
protocol, and the weaning protocol of each ICU.

3. Feedback meeting twice a month on occurrence of these AEs in the unit, causes, and
preventability

Study population All patients admitted to the four study ICUs after January, 2007 will be
included. No patients will be excluded. The study has been submitted to the appropriate
ethics committee.

Data collection Patients Data are collected in the Outcomerea database. For each patient,
the clinical research assistant will complete a case-report form on a computer using data
capture software (Rhea) then will import all records to the Outcomerea database. The
following information will be recorded prospectively: demographic characteristics (age, sex,
and body mass index); underlying diseases using the Knaus classification [8]; admission
category (medical, scheduled surgery, or unscheduled surgery), invasive procedures (arterial
or venous central catheter, Swan-Ganz catheter, and endotracheal intubation), nosocomial
infections (ventilator-associated pneumonia, nosocomial bacteremia, urinary tract
infections, surgical site infections, and sinusitis), and decisions to withhold and/or
withdraw life-sustaining treatments. The location of the patient prior to ICU admission will
be recorded, with transfer from wards being defined as admission to the same hospital or
another hospital before ICU admission. Severity of illness will be recorded at admission and
once a day thereafter. Day 1 is the interval from admission to 8 A.M. on the next day; all
other days are calendar days from 8 A.M. to 8 A.M. The Simplified Acute Physiology Score
(SAPS II) [9] at admission and the Logistic Organ Dysfunction (LOD) [10] score are computed
using the worst physical and laboratory data during the first 24 hours in the ICU. Duration
of stays in the ICU and acute-care hospital and vital status at ICU and hospital discharge
will be recorded.

Adverse events All AEs will be collected during all four periods, regardless of the
intervention being implemented. For each AE, Rhea software will be used to collect the date
and time of occurrence, clinical consequences (from a predefined list), therapeutic
consequences (from a predefined list), preventability, severity, and relation with death on
a five-item scale (excluded, very less unlikely, less unlikely, unlikely, likely,
certainly). An open box will be available for description of the AEs if needed.

Statistical analysis A hierarchical (patients/center) logistic model will be used to
evaluate the impact of each intervention. The intervention, as well as interactions between
periods and specific interventions, will be taken into account.