Ignite Creation Date:
2024-05-05 @ 5:32 PM
Last Modification Date:
2024-10-26 @ 9:33 AM
Study NCT ID:
NCT00479011
Status:
TERMINATED
Last Update Posted:
2007-05-25
First Post:
2007-05-24
Brief Title:
Intraoperative Fluid Management Based on Arterial Pulse Pressure Variation During High-Risk Surgery
Sponsor:
Santa Casa de Passos
Organization:
Santa Casa de Passos
Study Overview
Official Title:
Intraoperative Fluid Management Based on Arterial Pulse Pressure Variation During High-Risk Surgery
Status:
TERMINATED
Status Verified Date:
2007-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
significant reduction in length of hospital stay primary endpoint
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 ie of the position on the preloadstroke volume relationship Frank-Starling curve 9
By increasing cardiac preload volume loading induces a rightward shift on the preloadstroke 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
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 ie of the position on the preloadstroke volume relationship Frank-Starling curve 9
By increasing cardiac preload volume loading induces a rightward shift on the preloadstroke 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
Detailed Description:
Principal investigator Dr Marcel Rezende Lopes Department of Anesthesia and Critical Care Santa Casa de Misericórdia de Passos Passos MG Brazil marcelrlopesuolcombr
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 orand 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 weightheight2
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 12 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 12 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 005 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 MF Age yr Weight kg Height cm BMI kgm2 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 micromoll Prothrombin time Hemoglobin gdl 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 statusSTART of surgery Heart rate min Mean arterial pressure mmHg SpO2 PP Hemoglobin gdl
Physiologic statusEND of surgery Heart rate min Mean arterial pressure mmHg SpO2 PP Hemoglobin gdl 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 mlkgh Duration of surgery hours
Table 3 Patients characteristics after surgery
ICU admission Mean arterial pressure mmHg Heart rate bpm SpO2 Lactate mmoll
24 hr after ICU admission Mean arterial pressure mmHg Heart rate min SpO2 Vasoactive support if yes please indicate name and dosage Lactate mmoll Mean lactate over 24h mmoll
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 100000microl Prothrombin time 50
Renal Urine output 500 mlday Serum creatinine 170 micromoll Dialysis for acute renal failure
Total number of complications
References
1 Mythen MG Webb AR Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery Arch Surg 1995 130423-29
2 Sinclair S James S Singer M Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture a randomised controlled trial BMJ 1997 315909-12
3 Venn R Steele A Richardson P et al Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures Br J Anaesth 2002 8865-71
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
5 Conway DH Mayall R Abdul-Latif MS et al Randomized controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery Anaesthesia 2002 57845-49
6 Wakeling HG McFall MR Jenkins CS et al Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery Br J Anaesth 2005 95634-42
7 Noblett SE Snowden CP Shenton BK et al Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection Br J Surg 2006 931069-76
8 Lefrant JY Bruelle P Aya AG et al Training is required to improve the reliability of esophageal Doppler to measure cardiac output in critically ill patients Intensive Care Med 1998 24347-52
9 Michard F Changes in arterial pressure during mechanical ventilation Anesthesiology 2005 103 419-28
10 Bennett-Guerrero E Welsby I Dunn TJ et al The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine moderate-risk elective surgery Anesth Analg 1999 89514-19
11 Pearse R Dawson D Fawcett J et al Early goal-directed therapy after major surgery reduces complications and duration of hospital stay A randomised controlled trial Crit Care 2005 9R687-R693
12 Schulz KF Grimes DA Sample size calculations in randomised trials mandatory and mystical Lancet 2005 3651348-1353
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 orand 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 weightheight2
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 12 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 12 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 005 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 MF Age yr Weight kg Height cm BMI kgm2 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 micromoll Prothrombin time Hemoglobin gdl 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 statusSTART of surgery Heart rate min Mean arterial pressure mmHg SpO2 PP Hemoglobin gdl
Physiologic statusEND of surgery Heart rate min Mean arterial pressure mmHg SpO2 PP Hemoglobin gdl 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 mlkgh Duration of surgery hours
Table 3 Patients characteristics after surgery
ICU admission Mean arterial pressure mmHg Heart rate bpm SpO2 Lactate mmoll
24 hr after ICU admission Mean arterial pressure mmHg Heart rate min SpO2 Vasoactive support if yes please indicate name and dosage Lactate mmoll Mean lactate over 24h mmoll
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 100000microl Prothrombin time 50
Renal Urine output 500 mlday Serum creatinine 170 micromoll Dialysis for acute renal failure
Total number of complications
References
1 Mythen MG Webb AR Perioperative plasma volume expansion reduces the incidence of gut mucosal hypoperfusion during cardiac surgery Arch Surg 1995 130423-29
2 Sinclair S James S Singer M Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture a randomised controlled trial BMJ 1997 315909-12
3 Venn R Steele A Richardson P et al Randomized controlled trial to investigate influence of the fluid challenge on duration of hospital stay and perioperative morbidity in patients with hip fractures Br J Anaesth 2002 8865-71
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
5 Conway DH Mayall R Abdul-Latif MS et al Randomized controlled trial investigating the influence of intravenous fluid titration using oesophageal Doppler monitoring during bowel surgery Anaesthesia 2002 57845-49
6 Wakeling HG McFall MR Jenkins CS et al Intraoperative oesophageal Doppler guided fluid management shortens postoperative hospital stay after major bowel surgery Br J Anaesth 2005 95634-42
7 Noblett SE Snowden CP Shenton BK et al Randomized clinical trial assessing the effect of Doppler-optimized fluid management on outcome after elective colorectal resection Br J Surg 2006 931069-76
8 Lefrant JY Bruelle P Aya AG et al Training is required to improve the reliability of esophageal Doppler to measure cardiac output in critically ill patients Intensive Care Med 1998 24347-52
9 Michard F Changes in arterial pressure during mechanical ventilation Anesthesiology 2005 103 419-28
10 Bennett-Guerrero E Welsby I Dunn TJ et al The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine moderate-risk elective surgery Anesth Analg 1999 89514-19
11 Pearse R Dawson D Fawcett J et al Early goal-directed therapy after major surgery reduces complications and duration of hospital stay A randomised controlled trial Crit Care 2005 9R687-R693
12 Schulz KF Grimes DA Sample size calculations in randomised trials mandatory and mystical Lancet 2005 3651348-1353
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None