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.

Background:

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

In the intra-operative period, fasting,anaesthesia and surgery may affect the body’s physiological capacity  in controlling its external fluid andelectrolyte balance  and also theinternal balance between the various body fluid compartments(3).Majorityof anaesthetized patients undergoing surgery have functional intravascularvolume deficit even before surgery that may be due to fasting and bowelpreparations(4).Major surgeries cause significant tissue trauma andare associated with systemic inflammatory response leading to vasodilatationand capillary leakage . There could be major fluid shifts with third spacefluid loss associated  with severehaemorrhage that are difficult to estimate leading to inadequately correctedhypovolemia and inappropriate use of vasopressors. In addition anaestheticdrugs may cause variable degree of vasodilatory and myocardial depressingeffects leading to reduced effective intravascular circulating volume andhypotension. All these factors cause patients undergoing surgery at risk ofhemodynamic instability, tissue hypoperfusion and adverse surgical outcome. Thereforeperioperative fluid therapy has a direct bearing on outcome and prescriptionsshould be tailored to the needs of the patient. The practice of intra-operativefluid therapy has changed from routine standard therapy measuring and replacingestimated various losses to restrictive fluid strategy where third space lossesare not replaced. The goal of the fluid therapy in the elective setting is tomaintain the effective circulatory volume while avoiding interstitial fluidoverload whenever possible. Perioperative fluid approach and goal directedtherapy aiming to keep a neutral balance has shown to improve patient outcome (5,6).

With the revolutionary developments inthe area of hemodynamic monitoring the trend is moving more towardsnon-invasive ways of assessing fluid responsiveness. Traditionally used statichemodynamic parameters like central venous pressure (CVP), pulmonary capillarywedge pressure (PCWP) are of limited value in predicting fluid responsiveness. Onceconsidered gold standard in hemodynamic monitoring, Pulmonary Artery Catheterhas fallen into disrepute as it is more invasive and because technologicaladvances have given minimally invasive alternatives(7).In pastyears, many trials using different devices and goals have been published in theliterature demonstrating better outcomes in organ functions  and morbidity, or even mortality OesophagealDoppler has been used by many for guiding fluid management with good resultsbut its use is partially limited by the need for deep sedation  and experienced staff . Also, the reliabilityin major vascular procedures requiring cross-clamping of descendent aorta couldbe questioned(8).

With the introduction of arterialpressure waveform analysis, the well-known interaction between stroke volumevariation (SVV) and lung inflation during mechanical ventilation has becomeavailable for routine clinical use. Several studies documented the usefulnessof blood pressure variations and it surrogates (pulse pressure variation orsystolic pressure variation) in predicting position on the Frank-Starling curveand hence fluid responsiveness. They have been shown to be superior to staticindices and accurately predict fluid responsiveness in both ICU and surgicalpatients. (9)

Respirophasic radial artery pulsepressure variation (PP) has been shown to predict volume responsiveness inhemodynamically unstable patients receiving mechanical ventilation with apositive predictive value (PPV) and a negative predictive value (NPV) of 94%and 96%, respectively(10). But measurement of the PPV requiresinvasive monitoring with a peripheral arterial catheter, which has beenassociated with a risk of both infectious and embolic complications. Inaddition, measurement of the Pulse Pressure variation requires a specializedmonitoring setup that is unavailable in many setup.

Ultrasound technology has been used toaddress the specific limitations of indwelling arterial and Venous catheters. Aparadigm shift has occurred in the arena of hemodynamic monitoring which hasmade Doppler evaluation of brachial artery velocity time integral and carotidartery  velocity time integral as amethod of assessing fluid responsiveness. Its advantage is that it is totallynon-invasive bedside approach (11, 12,13,14).

Thus, we would like to test whether abrachial artery velocity time integral and carotid artery velocity timeintegral could substitute as an accurate, noninvasive surrogate for PulsePressure Variation in predicting fluid responsiveness in patients undergoingmajor surgeries with controlled mechanical ventilation.

Aims and Objective

To determine whether brachial arteryvelocity time integral and carotid artery velocity time integral couldsubstitute as an accurate, noninvasive surrogate for Pulse Pressure Variation inpredicting fluid responsiveness in patients undergoing major surgeries  withcontrolled mechanical ventilation.

Methods**:**

After approval by the institutionalethics committee and obtaining informed consent, the study will include 50readings from the patients who fit to the inclusion criteria. Written informedconsent from the patients will be taken a day prior to surgery. A maximum ofthree sets of readings before and after fluid bolus as decided by the treatingOT anesthesiologist will be allowed per patient in the study and the three setsof readings will be at least two hours apart .All the study patients will besedated, paralysed and ventilated using volume-control settings with tidalvolume of 6-8 ml/kg of predicted body weight as adjusted by the OTanesthesiologist and adjusted to a tidal volume of 8 mL/kg and PEEP of 5 cmsH2Ofor the study period.

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

Study Design

The hemodynamic and respiratoryvariables readings will be recorded at baseline, before and after fluid bolusgiven to the patient.

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

After a fluid bolus,we will record thesame parameters, i.e. heart rate (HR), systolic blood pressure (SBP), diastolicblood pressure (DBP), mean arterial pressure (MAP), cardiac index (CI), PPV,SVV, SV, Brachial artery velocity time integral, Carotid Velocity Time integraland 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 willbe taken by the respective OT anesthesiologist  as per thepresence of one or more clinical signs of acute circulatory failure, defined asa systolic blood pressure of less than 90mmHg (or a decrease of more than 50mmHg in previously hypertensive patients) or the need for vasopressor drugs;the presence of oliguria (urine output <0.5 ml/kg/min for at least twohours); the presence of tachycardia; a delayed capillary refilling; or thepresence of skin mottling, lactate levels > 2 mmol/l.A fluid challenge of5-10 ml/kg actual body weight of Ringer lactate will be given over 10 minutesas decided by the OT anesthesiologist.

Patients will be divided into twogroups 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 usedto obtain the measurements. A physician with previous formal training incritical care ultrasound will be obtaining Doppler measurements of velocitytime integral from the brachial artery and carotid artery.

Brachial Artery velocity time integral before and after fluidbolus

Arterial blood flow velocities will bemeasured from the brachial artery just proximal to the antecubital fossa in thearm contralateral to the arterial catheter over 30 secs. The velocity waveformwill be recorded from the midstream of the vessel lumen and the sample volumewill be adjusted to cover the center of the arterial vessel, in order to obtaina clear Doppler blood velocity time integral.

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

Carotid Artery velocity time integral before and after fluid bolus

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

Arterial pulse pressure variation before and after fluid bolus

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

Cardiac output and stroke volume variation measurements

A FloTrac sensor (Edwards LifesciencesLLC, Irvine, CA, USA) will be  connectedto 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 thereal-time analysis of the arterial waveform, using a proprietary algorithmbased on the relation between the arterial pulse pressure and stroke volume.After zeroing the system against atmosphere, the arterialwaveform signalfidelity will be checked using the square wavetest and hemodynamic measurementswill be initiated. CO, stroke volume and Δ Stroke Volume variation values will beobtained over a period of 30 seconds.

Statistics

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

 Sample Size

Assuming50% incidence of fluid responsiveness,it was determined that 50 readings  would be required to detect differences of0.15 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 of5%, and an estimated 20% attrition rate(14).