Aim and objectives:

a)      Primary objectives:

To study the effect of acute vasodilator testing with 100% oxygen on change in Pulmonary artery pressure  due to left heart disease

b)     Secondary objectives:

1.      Effect of 100% oxygen on change in Cardiac output, Pulmonary vascular resistance, Trans pulmonary gradient, Diastolic pulmonary gradient and Pulmonary capillary wedge pressure.

2.      To study the differences in effect of 100% oxygen on Pulmonary Hypertension due to Post capillary hypertension and combined Pre and Post Capillary Pulmonary hypertension.

3.      Correlation of responders vs non-responders to 100% oxygen with patients in whom fall in mean pulmonary arterial pressure will be more than Pulmonary capillary wedge pressure after left heart intervention.

1.      Methodology:

This study will be conducted in the departments of Anaesthesiology & critical care and cardiothoracic vascular surgery. The study will be approved by the institutional human ethics committee, and written informed consent will be obtained from all the participants.

A.    Study design:

Prospective Interventional study.

B.     Study participants (human, animals or both):

Humans

a.      Inclusion criteria

All elective cardiac surgery patients >18 years with left heart disease with estimated Right ventricular Systolic pressure (RVSP) > 40 mmHg by transthoracic echocardiography

b.      Exclusion criteria

i.                    Patients with shunt lesions like Atrial septal defect, Ventricular septal defect.

ii.                  Patients in whom pulmonary artery catheter insertion is contraindicated such as pnemonectomy, previous lung surgery, pulmonary valvular or infundibular stenosis, tricuspid stenosis, documented pulmonary artery branch obstruction

iii.                Patients in whom Transesophageal echocardiogram (TEE) placement is contraindicated like esophageal tumours, esophageal perforation, upper Gastrointestinal bleed.

iv.                 Arrythmias with hemodynamic instability

c.       Withdrawal criteria

i)                    Patients requiring Preincisional ionotrophic support.

ii)                  Pre incisional adverse cardiac events requiring intervention.

iii)                Persistent desaturation of less than 90 % saturation even with FiO2 up to 0.4.

d.      Rescue criteria

We will restore the original FiO2 in patients who desaturates with FiO2 up to 0.4.               

e.       Number of groups to be studied, identify groups with definition

One Group – Pulmonary pressures and hemodynamic parameters are measured at two different levels of Fractional inspired Oxygen concentration.

f.          Sampling population

All left heart disease patients with Right ventricular Systolic pressure > 40 mmHg calculated from Transthoracic Echo cardiography scheduled for elective cardiac surgery admitted by the Cardiothoracic and vascular surgery department in JIPMER.

g.      Samplesize calculation:

n=57

The sample size was determined by EZR software. The sample size was calculated based on the precedent study, where the mean difference of 10 mmHg in mean Pulmonary arterial pressure after acute vasodilator testing as clinically significant and a pooled standard deviation( SD) of 25 mmHg.¹⁰ With a power of 80% and an α level of 0.05, 52 subjects are required by using sample size for paired comparison. Considering the possibility of 10% dropouts, 57 patients were planned to be recruited.

h.      Sampling technique

Convenience sampling

C.     Randomization details:

 Intervention details with standardization techniques (drugs / devices / invasive procedures / noninvasive procedures / others)

Nil

D.    Study procedure:

After obtaining approval from departmental research monitoring committee and Institute ethics committee, patients with left heart disease with RVSP > 40 mmHg calculated from Transthoracic Echocardiogram, will be taken up for the study. Enrollment of the patients will be done after CTRI registration. A valid written informed consent will be obtained from the patients before enrolling into the study. Pre anaesthestic assessment will be done on the day before surgery. We follow the usual institutional established premedication protocol. All patients will be premedicated with tab diazepam 5 mg and tab famotidine 20 mg on the night before and on day of the surgery. Intramuscular morphine 0.1 mg/kg will be administered to all patients one hour prior to induction of anaesthesia.

Premedication, monitoring devices, induction, intubation, maintenance, anesthetic agents, ventilator settings and volume infusion will be decided by the attending consultant cardiac anesthesiologist. The routine monitoring devices will include Electro Cardio Gram (ECG), Invasive Blood Pressure (IBP), Central venous pressure (CVP), Temperature, airway pressure, End Tidal Carbon dioxide (EtCO2), monitoring of pulmonary artery pressure and Trans esophageal Echocardiography (TEE), Bispectral index (BIS).

According to our usual institution protocol, a standard induction protocol will be used for induction of general anaesthesia with inj.midazolam 0.05 mg/kg, inj.fentanyl 2-5 micrograms/kg, inj.thiopentone 3 - 5 mg/kg, inj vecuronium 0.1 mg/kg, inj.Xylocard 1.5 mg/kg. After intubation of trachea with appropriate size endotracheal tube, anaesthesia will be maintained with 1-2% Sevoflurane and 50:50 ratio of oxygen and air.

After induction of anesthesia, under strict aseptic precautions, the Sheath of Pulmonary Artery Catheter and a standard triple lumen central venous catheter will be inserted into Right Internal Jugular vein using Seldingers’ technique with Ultrasound (USG) guidance by consultant cardiac anesthetist, the sheath of the Pulmonary artery catheter (PAC) and central venous catheter will be secured by sutures to the skin.  TEE probe will be inserted as per standard procedure. Pulmonary artery catheter (Edward life sciences’ standard four port pulmonary artery catheter with thermistor)  will be negotiated into pulmonary artery under the guidance of TEE and PAC will be fixed at appropriate position.

Once all monitoring modalities are in place we will start the study by lowering Fractional Inspired oxygen concentration (FiO2) to 0.3 and flow rate will be adjusted to keep End tidal oxygen (EtO2) between 25 -30% for 10 minutes. End tidal Carbondioxide (EtCO2) during the course of study will be maintained between 30-40 mmHg.

Hemodynamic parameters like  mean pulmonary artery pressure (mPAP), Pulmonary artery Systolic Pressure (P-SBP), Pulmonary artery Diastolic pressure (P-DBP), Pulmonary capillary wedge pressure (PCWP), Cardiac output (CO) (measured by thermo dilution technique,  transpulmonary gradient (TPG), diastolic pulmonary gradient (DPG), Systemic vascular resistance (SVR), Pulmonary Vascular resistance (PVR), Right Ventricle Stroke Volume (RVSV), heart rate (HR), Systolic blood pressure(SBP), Diastolic Blood Pressure (DBP), Mean arterial blood pressure (MBP) will be measured three times at an interval of 2 minutes and average of three values will be calculated. 

Mixed venous oxygen saturation (SvO2), oxygen saturation (SpO2), end tidal Carbon dioxide (EtCO2), Central venous pressure (CVP), arterial blood gas parameters like, partial pressure of Oxygen (PaO2), pH, Partial pressure of carbon dioxide (PCO2) and peak airway pressure (PAP) and mean airway pressure (MAP) are measured.

 After first measurement, FiO2 will be increased to 1 and flow rate will be adjusted to keep EtO2 above 95% and patient will be ventilated to keep EtCO2 between 30 - 40 mmHg. After 10 minutes, same parameters will be measured again.  During this course of study, no additional fluids will be given, and BIS will be maintained between 50-70.

Surgery will commence once the first part of Study is over.  The management of the case during the CPB and post CPB will be according to the discretion of attending consultant anaesthesiologist.

After the surgical procedure during rewarming phase, Nitroglycerin infusion will be started in all patients at dose of 5 mcg /kg/ min as per institution protocol and dobutamine will be used to wean off from CPB. Appropriate dose of adrenaline and noradrenaline may be started in sequential order by attending consultant to maintain mean arterial pressure between 70-90mmHG. After skin closure the patient will be mechanically ventilated with FiO2 of 0.5 to flow rate will be adjusted to keep etO2 above 0.5. After 10 minutes the same parameters P-SBP, D-SBP, m-PAP, CO, SVR, PVR, RVSV, HR, SBP, DBP, MBP, TPG, DPG will be measured three times at 2-minute interval and average of three reading will be calculated.  SpO2, EtCO2 and blood gas parameters pH, PCO2, PaO2, PAP, MAP will be measured.

            After the completion of study as per institution protocol all patients will be shifted to cardiac intensive care unit (ICU) and will be kept on mechanical ventilator support. The post op management and removal of Pulmonary artery catheter in ICU will be on the discretion of attending ICU consultant.