Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT00479011 |
| Other study ID # |
marcelrlopes |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
May 24, 2007 |
| Last updated |
May 24, 2007 |
| Start date |
September 2005 |
| Est. completion date |
January 2006 |
Study information
| Verified date |
May 2007 |
| Source |
Santa Casa de Passos |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Brazil: National Committee of Ethics in Research |
| Study type |
Interventional
|
Clinical Trial Summary
Hypovolaemia and tissue hypoperfusion can pass undetected during and after major surgery.
The resulting systemic inflammatory response and organ dysfunction, often not clinically
apparent for several days, may lead to increased morbidity and mortality and prolonged
hospital stay.
In this regard, intraoperative optimization of circulatory status by volume loading has been
shown to improve the outcome of patients undergoing high-risk surgery.
Indeed, several reports (1-7) have shown that monitoring and maximizing stroke volume by
volume loading (until stroke volume reaches a plateau, actually the plateau of the
Frank-Starling curve) during high-risk surgery decreases the incidence of post-operative
complications and the length of hospital stay.
Unfortunately, this strategy has required so far the measurement of stroke volume by a
cardiac output monitor, as well as a specific training period for the operators (8), and
hence is not applicable in many institutions as well as in many countries.
The arterial pulse pressure variation (∆PP) induced by mechanical ventilation is known to be
a very accurate predictor of fluid responsiveness, i.e. of the position on the
preload/stroke volume relationship (Frank-Starling curve) (9).
By increasing cardiac preload, volume loading induces a rightward shift on the
preload/stroke volume relationship and hence a decrease in ∆PP. Patients who have reached
the plateau of the Frank-Starling relationship can be identified as patients in whom ∆PP is
low (9).
Therefore, the clinical and intraoperative goal of “maximizing stroke volume by volume
loading” can be achieved simply by minimizing ∆PP.
We designed the present study to investigate whether monitoring and minimizing ∆PP by volume
loading during high-risk surgery may improve post-operative outcome and decrease the
duration of post-operative hospital stay.
Description:
Principal investigator Dr. Marcel Rezende Lopes, Department of Anesthesia and Critical Care,
Santa Casa de Misericórdia de Passos, Passos MG, Brazil, marcelrlopes@uol.com.br
Study design Single centre randomized controlled trial
Investigation centre Department of Anesthesia and Critical Care, Santa Casa de Misericórdia
de Passos, Passos MG, Brazil
Inclusion criteria
- medico-surgical pre-operative decision of post-operative ICU admission (because of
co-morbidities or/and the surgical procedure)
- age > 18 yr
- elective surgery
Exclusion criteria
- no informed consent
- cardiac arrhythmias
- body mass index > 40
- patients undergoing surgery with an open thorax
- patients undergoing neurosurgery
- enrolment in any other protocol
Ethics committee The study has been approved by the ethical committee of Santa Casa de
Misericórdia de Passos (Passos, MG, Brazil).
Informed consent Written informed consent will be required for each patient.
Start date Sept 22, 2005
Finishing date January 23, 2006
Randomisation Randomisation will be done pre-operatively using sealed envelopes. Patients
will be assigned to a Control group (group C) or to an Intervention group (group I)
Intraoperative monitoring In group I, a specific multiparameter bedside monitor (DX 2020,
Dixtal, Sao Paulo, SP, Brazil) will be utilized to record continuously and simultaneously
the ECG, the pulse oximetry signal, the arterial pressure curve and the capnographic signal.
A specific software is uploaded into this monitor, allowing the recognition of respiratory
cycles (from the analysis of the capnographic signal) and the automatic calculation and
display of ∆PP.
Intervention During the surgical procedure, patients will be managed according to standard
of care at Santa Casa de Misericórdia de Passos.
Group C will receive per-operative fluid at the discretion of the anesthetist. Group I will
receive additional hydroxyethylstarch 6% (HES) boluses in order to minimize and maintain ∆PP
≤ 10%. During the postoperative period, both groups will be managed by intensivists (in the
ICU) and clinicians (in the wards) not involved in the intraoperative management nor in data
collection. These individuals will not be informed of patient allocation.
Data collection Over the study period all data will be collected prospectively. Patients
will be followed up until hospital discharge.
Data collection prior to surgery Parameters to be recorded before the surgical procedure are
presented in table 1.
The body mass index is calculated according to the standard formula (BMI = weight/height2).
Serum creatinine, prothrombin time, hemoglobin, and platelets will be obtained from routine
pre-operative biological tests.
Data collection during surgery Parameters to be recorded during the surgical procedure are
presented in table 2.
Data collection after surgery Data collection prior to and during surgery will be done by
one individual. Data collection after surgery will be done by another individual not aware
of patient allocation.
Information and parameters to be collected after surgery are presented in tables 3 and 4.
During the 24h following ICU admission, blood lactate will be measured every 6h and the mean
lactate value will be calculated over the first 24h ICU period.
Postoperative infectious, respiratory, cardiovascular, abdominal, hematologic, and renal
complications (table 4) will be recorded according to criteria previously used by other
investigators (10-11).
Duration of mechanical ventilation, of ICU stay, and of hospital stay, as well as hospital
mortality will be recorded too.
Data will be collected systematically at days 1,2, and 5, as well as at ICU discharge, and
hospital discharge.
Statistical analysis Data will be analysed comparing patients in group C with those in group
I on an intention-to-treat basis.
The primary outcome measure is the duration of postoperative hospital stay. On the basis of
our own hospital registry, the mean duration of postoperative hospital stay in group C is a
priori estimated at 16 ± 8 days (mean ± SD).
According to previous publications (1,2), we postulated that the mean duration of
postoperative hospital stay in group I could be 35% lower.
A sample size of 33 patients in each group was calculated for a 0.05 difference (two sided)
with a power of 80% (12).
Secondary outcome measures are the number of post-operative complications per patient, as
well as the duration of mechanical ventilation and ICU stay.
Interim analyses and stopping rules An intermediate analysis after the enrolment of the
first 33 patients is planed, in order to readjust the population sample size if necessary,
or to stop the trial in case a significant reduction in length of hospital stay (primary
endpoint) is observed.
Role of funding source Dixtal (Sao Paulo, SP, Brazil) will provide and upload the automatic
calculation software in a bedside monitor owned by Santa Casa de Misericórdia de Passos
(Passos, MG, Brazil).
Dixtal had no role in the study design, and will have no role in data collection, data
analysis, data interpretation, or writing of the report. The corresponding author (Dr F.
Michard) will have full access to all data in the study and will have final responsibility
for the decision to submit for publication.
Table 1: Patients characteristics before surgery:
- Sex M/F, Age (yr), Weight (kg), Height (cm), BMI (kg/m2), ASA physical status
- Chronic disease: Renal failure requiring dialysis, Renal failure without dialysis,
Cirrhosis, Chronic obstructive pulmonary disease, Hypertension, Peripheral vascular
disease, Coronary artery disease, Other cardiopathy, Diabetes mellitus, Cerebrovascular
disease
- Pre-operative biological tests: Serum creatinine (micromol/l), Prothrombin time (%),
Hemoglobin (g/dl), Platelets (/microl)
Table 2: Patients characteristics during surgery:
- Type of surgery: Upper gastro-intestinal, Hepato-biliary, Lower gastro-intestinal,
Urology, Other
- Respiratory settings: Tidal volume (mL), Respiratory frequency (/min)
- Physiologic status/START of surgery: Heart rate (/min), Mean arterial pressure (mmHg),
SpO2(%), ∆PP (%), Hemoglobin (g/dl)
- Physiologic status/END of surgery: Heart rate (/min), Mean arterial pressure (mmHg),
SpO2 (%), ∆PP (%), Hemoglobin (g/dl), Fluid balance, Volume of crystalloid infused
(ml), Volume of colloid infused (ml), Volume of red cells infused (ml), Volume of fresh
frozen plasma infused (ml), Total volume infused (ml), Total volume infused (ml/kg/h),
Duration of surgery (hours)
Table 3: Patients characteristics after surgery:
- ICU admission : Mean arterial pressure (mmHg), Heart rate (bpm), SpO2 (%), Lactate
(mmol/l)
- 24 hr after ICU admission: Mean arterial pressure (mmHg), Heart rate (/min), SpO2 (%),
Vasoactive support (if yes please indicate name and dosage), Lactate (mmol/l), Mean
lactate over 24h (mmol/l)
Table 4: Post-operative complications
- Infection: Pneumonia, Abdominal, Urinary tract, Central venous catheter, Wound
- Respiratory: Pleural effusion, Pneumothorax, Pulmonary embolism, Respiratory support >
24 h, Acute lung injury
- Cardiovascular: Arrhythmia, Hypotension, Acute pulmonary edema, Acute myocardial
infarction, Cardiac arrest, Stroke
- Abdominal: Clostridium difficile diarrhoea, Acute bowel obstruction, Upper
gastro-intestinal bleed, Anastomotic leak
- Coagulopathy: Platelet count < 100000/microl, Prothrombin time < 50%
- Renal: Urine output < 500 ml/day, Serum creatinine > 170 micromol/l, Dialysis for acute
renal failure
- Total number of complications
References
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mucosal hypoperfusion during cardiac surgery. Arch Surg 1995; 130:423-29.
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influence of the fluid challenge on duration of hospital stay and perioperative
morbidity in patients with hip fractures. Br J Anaesth 2002; 88:65-71.
4. Gan TJ, Soppitt A, Maroof M, et al. Goal-directed intraoperative fluid administration
reduces length of hospital stay after major surgery. Anesthesiology 2002; 97: 820-26.
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