Viva 6

How will you monitor the response to your interventions? What  are your therapeutic endpoints?

As far as specific parameters go, this is an evidence-free wasteland. One can choose any author from the literature and use their totally arbitrary numbers. For example, Ellis et al (1997) recommends in an authoritative non-EBM fashion to aim for the following parameters:

• CI > 2.0 L/min/m²
• CVP 8-10
• PCWP 12-15 (16-20 if the LV is hypertrophied)
• u/o >0.5ml/kg/hr
• Lactate on a down-trend
• MAP > 70

With inotropes commenced and PEEP rationalised, a thermodilution measurement is performed. Please interpret this data and explain how it affects your management.

The following abnormalities are apparent:

• Tachycardia
• Raised CVP (21)
• Raised PCWP (24)
• Raised PA mean pressure (42; normal is 9-18)
• Low stroke volume (SV= 41;  normal is 60-100)
• Low SVRI (1753; normal is 1950-2390)
• High PVRI (554; normal is 255-285)
• Satisfactory CI and SvO₂

Overall, this gives the impression of a patient with predominantly right-sided cardiac pathology, with high pulmonary pressures and systemic vasodilation. The cardiac output is now satisfactory.

What are the potential causes of raised pulmonary pressures after cardiac surgery?

Denault et al (2010) offer an excellent article on this topic; the following list is derived from their Figure 5

• Positive pressure ventilation with excessive pressures
• Mechanical compression of pulmonary vessels by
  • Atelectatic lung or effusions
  • Distended abdomen
  • Enlarged mediastinal structures, eg. pericardial effusion
• Underlying disease (pre-existing PHT)
• LV dysfunction with increased LV end-diastolic pressures
• Mitral regurgitation or stenosis
• Pulmonary inflammation
• Metabolic or respiratory acidosis
• Hypoxia due to atelectasis
• Protamine administration; excess noradrenaline
• Pulmonary emboli

What are the options for managing this pulmonary hypertension?

IV pulmonary vasodilators:

• Milrinone
• Levosimendan
• Intravenous prostacycline

Inhaled vasodilators:

• Nitric oxide
• Inhaled prostacycline

(the trainee should not be talking about sildenafil or bosantan here, as the patient is not going to absorb anything much orally and in any case immediate results are called for)

Metabolic manipulation

• Correct acidosis
• Ensure normocapnia and normoxia

Mechanical decompression

• Decrease PEEP
• Drain effusions/pneumothoraces

The department has only nitric oxide available. Can you explain its mechanism of action?

• Nitric oxide is a potent vasodilator
• It inhibits vasoconstriction by increasing the amount of cyclic GMP (cGMP) in the cytosol,
• This decreases the amount of cytosolic calcium ions available to sustain contraction

What form does it come in? What are the pharmacokinetics of inhaled nitric oxide?

• The gas comes in a pressurised cylinder, under a brand name "INOmax".
• It contains 99.92% nitrogen and only 0.08% nitric oxide, or 800 parts per million (ppm).
• The highest concentration you would ever use is about 80ppm, which corresponds to a gas mixture of 90% whatever, and 10% Inomax.
• Nitric oxide is rapidly absorbed into the systemic circulation through the lungs
• In the blood it undergoes some significant modifications:
  • It reacts with lung water, becoming nitrite (which reacts with oxyhemoglobin and generates methaemoglobin and nitrate)
  • It combines directly with oxyhaemoglobin, with the same results.
  • If it encounters hypoxic blood, it can combine with deoxyhaemoglobin to create nitrosyl-haemoglobin, which then rapidly becomes methaemoglobin when it contacts oxygen.
  • In all cases, it generates methaemoglobin and nitrate

What are the contraindications for the use of inhaled nitric oxide?

• Left ventricular failure: NO seems to cause lots of adverse effects in this group of patients- particularly, pulmonary oedema. In fact, halfway through one study, the investigators had to start excluding CCF patients from the trial because of these effects.
• Left to right shunting: NO will decrease the pulmonary (and thus the RV) pressure, increasing the amount of blood shunted via a septal defect.
• Uncontrolled haemorrhage: Though there is no human evidence, in animal studies NO had been shown to increase bleeding times.
• Existing methaemoglobinaemia: obviously, it will get worse. 

Several hours after commencement of inhaled nitric oxide, the nurses complain that the patient's saturation remains very low (~ 85%) on 100% FiO₂. They have performed the following ABG. Please interpret it and explain the major abnormalities

There is:

• Mild acidaemia
• Normocapnea
• Normal normal oxygen saturation (99%) contrary to the pulse oximeter reading - in fact, you could safely come down on the oxygen
• Mild lactic acidosis
• Methaemoglobinaemia (FMetHb is 28.8%)

Can you explain why the pulse oximeter reading is affected in this scenario?

There is a great article on this (Barker et al, 1989). In brief:

• Oxygen saturation is the ratio of reduced haemoglobin to oxyhaemoglobin
• Reduced haemoglobin and oxyhaemoglobin absorb different wavelengths;
  • Reduced Hb absorbs red light (660nm)
  • Oxygenated Hb absorbs infra-red light (940nm)
• The pulse oximeter only uses these two wavelengths to calculate a red/infrared absorption ratio, or R value
• The absorbance spectrum of methaemoglobin for red and infrared is very similar, and the R value is therefore close to 1 (which in the pulse oximeter look-up table corresponds to a saturation of around 82%
• Thus, increasing methaemoglobin levels will result in a pulse oximeter reading which trends towards 82%. A plateau is reached at an FMetHb of around 30-35%.

Apart from methaemoglobinaemia, what are the other adverse effects of inhaled nitric oxide?

Nitric oxide is genotoxic. It damages DNA in a vicious, direct fashion. On top of that, the following adverse effects have been reported:

• Hypotension (maybe some of it does leak into the systemic circulation, or maybe this the effect of depressed LV function
• Rebound hypoxia after abrupt withdrawal
• Thrombocytopenia (in as many as 10% of patients)
• Increased susceptibility to pulmonary infections probably due to NO₂ formation and associated lung injury.