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CTRI Number  CTRI/2017/08/009243 [Registered on: 03/08/2017] Trial Registered Prospectively
Last Modified On: 31/07/2017
Post Graduate Thesis  Yes 
Type of Trial  Observational 
Type of Study   Prospective Observational 
Study Design  Other 
Public Title of Study   To see whether measuring blood pressure change correlates with measuring speed & time of flowing of major blood vessels in pts undergoing major surgeries under generl anesthesia on artificial breathing machine that can help in identifying which pts will get benefited frm giving fluids. 
Scientific Title of Study   To determine whether Pulse Pressure Variation correlates with Brachial artery velocity time integral and Carotid velocity time integral in predicting fluid responsiveness in patients undergoing major surgeries under general anesthesia with controlled mechanical ventilation. 
Trial Acronym  nil 
Secondary IDs if Any  
Secondary ID  Identifier 
1883_Protocol_V_1.1  Protocol Number 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Dr Malini Joshi 
Designation  Professor 
Affiliation  Tata Memorial Hospital,Parel,Mumbai 
Address  Tata Memorial Hospital Parel Mumbai
Tata Memorial Hospital,Parel Mumbai
Mumbai
MAHARASHTRA
400012
India 
Phone  91-9987226657  
Fax  91-22-24146937  
Email  jmalini2007@rediffmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Dr Malini Joshi 
Designation  Professor 
Affiliation  Tata Memorial Hospital,Parel,Mumbai 
Address  Tata Memorial Hospital Parel Mumbai
Tata Memorial Hospital,Parel Mumbai
Mumbai
MAHARASHTRA
400012
India 
Phone  91-9987226657  
Fax  91-22-24146937  
Email  jmalini2007@rediffmail.com  
 
Details of Contact Person
Public Query
 
Name  Dr Pravin Dhakne 
Designation  Junior Resident 
Affiliation  Tata Memorial Hospital 
Address  Tata Memorial Hospital,Parel Mumbai
Tata Memorial Hospital,Parel,Mumbai
Mumbai
MAHARASHTRA
400012
India 
Phone  91-9860292012  
Fax  91-22-24146937  
Email  dhakane.pravin9@gmail.com  
 
Source of Monetary or Material Support  
Dept. of Anaesthesia, Critical Care and Pain, Tata Memorial Hospital, Parel, Mumbai-400012 
 
Primary Sponsor  
Name  Tata Memorial Centre 
Address  Dr. E. Borges Road, Parel, Mumbai-400 012 India 
Type of Sponsor  Research institution and hospital 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
Dr Malini Joshi  Tata Memorial Centre  Dept. of Anaesthesia, Critical care and Pian, Main Building Tata Memorial Hospital Parel- 400012
Mumbai
MAHARASHTRA 
9987226657

jmalini2007@rediffmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
IEC II, Tata Memorial Centre  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Patients  Adult patients undergoing elective surgeries having major blood loss or fluid shifts requiring cardiac output monitoring under general anaesthesia ,  
 
Intervention / Comparator Agent  
Type  Name  Details 
Intervention  Nil  Nil 
Comparator Agent  Nil  Nil 
 
Inclusion Criteria  
Age From  18.00 Year(s)
Age To  75.00 Year(s)
Gender  Both 
Details  1.Adult patients (Age > 18 yrs )
2.Elective surgeries cases having major blood loss or fluid shifts requiring cardiac output monitoring under general anaesthesia
3.Receiving lung ventilation 8 ml/kg PBW using Volume Assist Control mode.
4.With invasive arterial blood pressure monitoring and cardiac output monitoring using Flotrac EV1000
 
 
ExclusionCriteria 
Details  1.Age under 18 years
2.Patient in whom brachial artery could not be identified with certainty viz above elbow amputated patients and patient with known PVD.
3.absence of sinusrhythm,
4.presence of a ventricular assist device
5.Carotid artery stenosis( common carotid artery stenosis greater than 50 %(systolic peak velocity >182 cm/s and/or diastolic velocity >30 cm/s by Doppler ultrasound)-as assessed by clinician from critical care with previous formal training in critical care ultrasound
6.contraindication to the prespecified ventilatory parameters (a period of passive ventilation at tidal volume [Vt] 8 mL/kg of predicted body weight
7.Known heart failure and LVEF< 40%
8.Valvular heart disease
9.Aortic insufficiency
10.Air leakage through chest drains
11.spontaneous respiratory efforts
 
 
Method of Generating Random Sequence   Not Applicable 
Method of Concealment   Not Applicable 
Blinding/Masking   Not Applicable 
Primary Outcome  
Outcome  TimePoints 
To determine whether brachial artery velocity time integral and carotid artery velocity time integral could substitute as an accurate, noninvasive surrogate for Pulse Pressure Variation in predicting fluid responsiveness in patients undergoing major surgeries with controlled mechanical ventilation  before and after fluid bolus  
 
Secondary Outcome  
Outcome  TimePoints 
Nil  Nil 
 
Target Sample Size   Total Sample Size="20"
Sample Size from India="20" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   30/08/2017 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="1"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   None yet 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Brief Summary  

Background:

The anesthesiologists role in predicting and assessing the hemodynamic responsiveness to volume expansion (VE) during the intra-operative period is among the most challenging and important part of the major surgeries. Intra-operative hypovolemia is common and may be a potential cause of organ dysfunction, increased postoperative morbidity, and death in major surgeries. But in studies designed to measure changes in cardiac index following fluid administration in hypotensive patients receiving mechanical ventilation,28 to 60% of patients showed no significant change(1).Fluids may not only be ineffective but harmful as well in some cases, as suggested by the results of the ARDS Network Fluid and Catheter Treatment Trial(2).

In the intra-operative period, fasting, anaesthesia and surgery may affect the body’s physiological capacity  in controlling its external fluid and electrolyte balance  and also the internal balance between the various body fluid compartments(3).Majority of anaesthetized patients undergoing surgery have functional intravascular volume deficit even before surgery that may be due to fasting and bowel preparations(4).Major surgeries cause significant tissue trauma and are associated with systemic inflammatory response leading to vasodilatation and capillary leakage . There could be major fluid shifts with third space fluid loss associated  with severe haemorrhage that are difficult to estimate leading to inadequately corrected hypovolemia and inappropriate use of vasopressors. In addition anaesthetic drugs may cause variable degree of vasodilatory and myocardial depressing effects leading to reduced effective intravascular circulating volume and hypotension. All these factors cause patients undergoing surgery at risk of hemodynamic instability, tissue hypoperfusion and adverse surgical outcome. Therefore perioperative fluid therapy has a direct bearing on outcome and prescriptions should be tailored to the needs of the patient. The practice of intra-operative fluid therapy has changed from routine standard therapy measuring and replacing estimated various losses to restrictive fluid strategy where third space losses are not replaced. The goal of the fluid therapy in the elective setting is to maintain the effective circulatory volume while avoiding interstitial fluid overload whenever possible. Perioperative fluid approach and goal directed therapy aiming to keep a neutral balance has shown to improve patient outcome (5,6).

With the revolutionary developments in the area of hemodynamic monitoring the trend is moving more towards non-invasive ways of assessing fluid responsiveness. Traditionally used static hemodynamic parameters like central venous pressure (CVP), pulmonary capillary wedge pressure (PCWP) are of limited value in predicting fluid responsiveness. Once considered gold standard in hemodynamic monitoring, Pulmonary Artery Catheter has fallen into disrepute as it is more invasive and because technological advances have given minimally invasive alternatives(7).In past years, many trials using different devices and goals have been published in the literature demonstrating better outcomes in organ functions  and morbidity, or even mortality Oesophageal Doppler has been used by many for guiding fluid management with good results but its use is partially limited by the need for deep sedation  and experienced staff . Also, the reliability in major vascular procedures requiring cross-clamping of descendent aorta could be questioned(8).

With the introduction of arterial pressure waveform analysis, the well-known interaction between stroke volume variation (SVV) and lung inflation during mechanical ventilation has become available for routine clinical use. Several studies documented the usefulness of blood pressure variations and it surrogates (pulse pressure variation or systolic pressure variation) in predicting position on the Frank-Starling curve and hence fluid responsiveness. They have been shown to be superior to static indices and accurately predict fluid responsiveness in both ICU and surgical patients. (9)

Respirophasic radial artery pulse pressure variation (PP) has been shown to predict volume responsiveness in hemodynamically unstable patients receiving mechanical ventilation with a positive predictive value (PPV) and a negative predictive value (NPV) of 94% and 96%, respectively(10). But measurement of the PPV requires invasive monitoring with a peripheral arterial catheter, which has been associated with a risk of both infectious and embolic complications. In addition, measurement of the Pulse Pressure variation requires a specialized monitoring setup that is unavailable in many setup.

Ultrasound technology has been used to address the specific limitations of indwelling arterial and Venous catheters. A paradigm shift has occurred in the arena of hemodynamic monitoring which has made Doppler evaluation of brachial artery velocity time integral and carotid artery  velocity time integral as a method of assessing fluid responsiveness. Its advantage is that it is totally non-invasive bedside approach (11, 12,13,14).

Thus, we would like to test whether a brachial artery velocity time integral and carotid artery velocity time integral could substitute as an accurate, noninvasive surrogate for Pulse Pressure Variation in predicting fluid responsiveness in patients undergoing major surgeries with controlled mechanical ventilation.

Aims and Objective

To determine whether brachial artery velocity time integral and carotid artery velocity time integral could substitute as an accurate, noninvasive surrogate for Pulse Pressure Variation in predicting fluid responsiveness in patients  undergoing major surgeries  with controlled mechanical ventilation.

Methods:

After approval by the institutional ethics committee and obtaining informed consent, the study will include 50 readings from the patients who fit to the inclusion criteria. Written informed consent from the patients will be taken a day prior to surgery. A maximum of three sets of readings before and after fluid bolus as decided by the treating OT anesthesiologist will be allowed per patient in the study and the three sets of readings will be at least two hours apart .All the study patients will be sedated, paralysed and ventilated using volume-control settings with tidal volume of 6-8 ml/kg of predicted body weight as adjusted by the OT anesthesiologist and adjusted to a tidal volume of 8 mL/kg and PEEP of 5 cmsH2O for the study period.

The Pulse Pressure Variation (PPV) will be recorded using the Philips Intel View Monitor (MP 70) and SVV, SV and cardiac index (CI) will be recorded from cardiac output monitor (FlotracEV1000) as/decided by the treating OT anesthesiologist one day prior to the surgery. The arterial pressure transducer will be attached to the patient’s upper arm at the level of the cardiac cavities. Demographic data of patients including age, sex, height, weight, predicted body weight (PBW), primary diagnosis and details of surgery will be recorded. Dose of vasopressors used if any, will be recorded. Supportive therapies, ventilatory settings and vasopressor therapy will be kept unchanged throughout the study time. Indications for the fluid challenge will be noted. The respiratory and hemodynamic parameters will be recorded at various intervals as per study design

Study Design

The hemodynamic and respiratory variables readings will be recorded at baseline, before and after fluid bolus given to the patient.

We will take readings of following hemodynamic parameters at baseline, prior to the fluid bolus and after fluid bolus -.Readings taken will include  heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), cardiac index (CI), Pulse Pressure Variation, Stroke Volume Variation, Stroke Volume, Brachial artery velocity time integral, Carotid artery velocity time integral (VTi) and respiratory variables like tidal volume, Ppeak, Pplateau and  the ratio of the heart rate and respiratory rate (HR/RR)

After a fluid bolus,we will record the same parameters, i.e. heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), cardiac index (CI), PPV, SVV, SV, Brachial artery velocity time integral, Carotid Velocity Time integral and respiratory variables like tidal volume,  P peak, P plateau and the ratio of the heart rate and respiratory rate (HR/RR)

The decision for volume expansion will be taken by the respective OT  anesthesiologist  as per the presence of one or more clinical signs of acute circulatory failure, defined as a systolic blood pressure of less than 90mmHg (or a decrease of more than 50 mmHg in previously hypertensive patients) or the need for vasopressor drugs; the presence of oliguria (urine output <0.5 ml/kg/min for at least two hours); the presence of tachycardia; a delayed capillary refilling; or the presence of skin mottling, lactate levels > 2 mmol/l.A fluid challenge of 5-10 ml/kg actual body weight of Ringer lactate will be given over 10 minutes as decided by the OT anesthesiologist.

Patients will be divided into two groups Responders and Non-Responders based on increase in stroke volume (SV) increased ≥ 15%after giving the fluid bolus(VE).

A SonoSite Titan HCU (SonoSite; Bothell, WA) device with a5-MHz broadband linear array transducer will be used to obtain the measurements. A physician with previous formal training in critical care ultrasound will be obtaining Doppler measurements of velocity time integral from the brachial artery and carotid artery.

Brachial Artery velocity time integral before and after fluid bolus

Arterial blood flow velocities will be measured from the brachial artery just proximal to the antecubital fossa in the arm contralateral to the arterial catheter over 30 secs. The velocity waveform will be recorded from the midstream of the vessel lumen and the sample volume will be adjusted to cover the center of the arterial vessel, in order to obtain a clear Doppler blood velocity time integral.

Clinicians obtaining ultrasound images will be blinded to the results of the arterial pulse pressure variations that will be collected independently by another clinician. All image angles will be corrected up to 15° for the best signal and stored for immediate review following each measurement. The brachial artery velocity time integral will be calculated over a period of 30 seconds 

Carotid Artery velocity time integral before and after fluid bolus

Carotid velocity time integral will be measured after procuring a longitudinal view of the common carotid artery, pulsed Doppler analysis at 2 cm from the bifurcation will be performed. The sample volume will be positioned at the center of the vessel, with angulation at no more than 60°. The carotid artery velocity time integral will be calculated over 30 seconds.

Arterial pulse pressure variation before and after fluid bolus

Radial arterial pressure pulse pressure variation will be recorded simultaneously with the ultrasound measurement of the Brachial Artery and carotid artery velocity time integral and by a clinician blinded to the ultrasound results.

Cardiac output and stroke volume variation measurements

A FloTrac sensor (Edwards Lifesciences LLC, Irvine, CA, USA) will be  connected to the arterial line and attached to the Vigileo monitor, software version 1.10 (Edwards Lifesciences LLC, Irvine, CA, USA). The CO will be calculated from the real-time analysis of the arterial waveform, using a proprietary algorithm based on the relation between the arterial pulse pressure and stroke volume. After zeroing the system against atmosphere, the arterialwaveform signal fidelity will be checked using the square wavetest and hemodynamic measurements will be initiated. CO, stroke volume and Δ Stroke Volume variation values will be obtained over a period of 30 seconds.

Statistics

Non-parametric tests will be applied for the data which is not normally distributed. Results will be expressed as median and interquartile range (25th to 75th percentiles). Patients will be classified according to stroke volume index (SVi) increase after VE in responders (≥15%) and nonresponders (<15%), respectively. The effects of VE on hemodynamic parameters will be assessed using the Wilcoxon rank sum test. Differences between responder and nonresponder patients will be established by the Mann-Whitney U test. The rate of vasopressor treatment will be compared between responder and nonresponder patients using the chi-squared test. The relations between variables will be analyzed using a linear regression method. The area under the receiver operating characteristic (ROC) curves for Carotid VTI and Brachial VTI, ΔPP radial, ΔSVVigileo and according to fluid expansion response will be calculated and compared using the Hanley-McNeil test. ROC curves will be presented as area ± standard error (95% confidence interval (CI)). A P value less than 0.05 will be considered statistically significant. Statistical analyses will be performed using SPSS 24 version

 

Sample Size

Assuming 50% incidence of fluid responsiveness,it was determined that 50 readings  would be required to detect differences of 0.15 between the areas under the receiver operating characteristic (AUROC) curve of PPV (0.63) and DVpeak-CA (0.88) with an 80% power and type I error of 5%, and an estimated 20% attrition rate(14).

 
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