Primary pulmonary hypertension (PAH) is a rare disease with an incidence of one to two cases per million people in the general population. While the majority of cases of pulmonary hypertension not associated with other medical conditions are sporadic, familial autosomal dominant inheritance accounts for 10% of these cases. The median period of survival after a diagnosis of idiopathic PAH is 2.8 years, with most patients succumbing to progressive right ventricular (RV) failure. Patients with idiopathic PAH are at risk of perioperative RV failure, hypoxemia, and coronary ischemia. Their risk may be as high as 28% for respiratory failure, 12% for cardiac dysrhythmias, 11% for congestive heart failure, and 7% for overall perioperative mortality for noncardiac surgery.
The pulmonary arteries normally have a systolic pressure of 18 to 25 mm Hg, a diastolic pressure of 6 to 10 mm Hg, and a mean pressure of 12 to 16 mm Hg. Pulmonary arterial hypertension is defined as a mean pulmonary artery pressure higher than 25 mm Hg at rest or higher than 30 mm Hg with exercise. Idiopathic PAH, previously called primary pulmonary hypertension, is that which occurs in the absence of left-sided heart disease, myocardial disease, congenital heart disease, and any clinically significant respiratory, connective tissue, or chronic thromboembolic disease. With idiopathic PAH, pulmonary artery occlusion pressure is no more than 15 mm Hg, and pulmonary vascular resistance (PVR) is higher than 3 Wood units (mm Hg/L/min) ( Table 5-9 ).
PVR is expressed in dynes/sec/cm-5, with normal PVR = 50–150 dynes/sec/cm-5
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PVR is expressed in Wood units (mm Hg/L/min), with normal PVR = 1 Wood unit
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PAH often presents with vague symptoms including breathlessness, weakness, fatigue, and abdominal distention. Syncope and angina pectoris are indicative of severe limitations of cardiac output and possible myocardial ischemia.
On physical examination, the patient may exhibit a parasternal lift, murmurs of pulmonic insufficiency (Graham-Steell murmur) and/or tricuspid regurgitation, a pronounced pulmonic component of S2, an S3 gallop, jugular venous distention, peripheral edema, hepatomegaly, and ascites.
The laboratory evaluation and diagnostic studies used in the workup of pulmonary hypertension of any cause are listed in Table 5-11 . A 6-minute walk test can be administered to assess functional status and noninvasively follow the progress of therapy. Right heart catheterization provides a definitive means to determine disease severity and to ascertain which patients can respond to vasodilator therapy. A potent vasodilator such as prostacyclin, NO, adenosine, or prostaglandin E1 is administered. The vasodilator test is considered positive, i.e., the patient is a responder, if PVR and mean pulmonary arterial pressure both decrease acutely by 20% or more. Only about one fourth of patients will have a favorable response to the vasodilator test.
Diagnostic Modality
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Key Findings
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Chest radiograph
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Electrocardiography
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Two-dimensional echocardiography
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Pulmonary function tests
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V/Q scan
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Pulmonary angiography
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Chest CT scan
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Abdominal ultrasound or CT scan
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Blood tests
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Sleep study
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The normal pulmonary circulation can accommodate flow rates ranging from 6 to 25 L/min with minimal changes in pulmonary artery pressure. As a result of pulmonary vasoconstriction, vascular wall remodeling and thrombosis in situ, PAH develops. RV wall stress increases in response to the increase in afterload produced by pulmonary hypertension. Both RV stroke volume and the volume available for left ventricular filling are reduced, leading to low cardiac output and systemic hypotension. RV dilation in response to the increased wall stress results in annular dilation of right-sided heart valves producing tricuspid regurgitation and/or pulmonic insufficiency. The right ventricle receives coronary blood flow during both systole and diastole. RV myocardial perfusion can be dramatically limited as RV wall stress increases and RV systolic pressure approaches systemic systolic pressure.
Patients with PAH are at risk of hypoxemia by three mechanisms: (1) as right-sided pressures increase, right-to-left shunting can occur through a patent foramen ovale; (2) in the presence of a relatively fixed cardiac output, the increased oxygen extraction associated with exertion will produce hypoxemia; and (3) V/Q mismatch can result in perfusion of poorly ventilated alveoli. If hypoxic pulmonary vasoconstriction occurs, overall pulmonary hypertension will be worsened.
Oxygen therapy can be helpful in reducing the magnitude of hypoxic pulmonary vasoconstriction. It has been studied primarily in patients with chronic obstructive pulmonary disease, and in this situation, it clearly improves survival and reduces progression of pulmonary hypertension. Anticoagulation may be recommended because of the increased risk of thrombosis and thromboembolism due to sluggish pulmonary blood flow, dilation of the right heart, venous stasis, and the limitation in physical activity imposed by this disease. Diuretics can be used to decrease preload in patients with right heart failure, especially when hepatic congestion, ascites, and severe peripheral edema are present.
The first class of drugs to provide dramatic long-term benefit in patients with PAH was calcium channel blockers. Calcium channel blockers are administered to patients who exhibit a positive response to a vasodilator trial in the cardiac catheterization laboratory. Nifedipine, diltiazem, and amlodipine are the most commonly used calcium channel blockers for this purpose and have been shown to improve 5-year survival.
Phosphodiesterase inhibitors produce pulmonary vasodilation and improve cardiac output. Sildenafil (Viagra) administration has been associated with improved exercise capacity and reduction in RV mass, although long-term mortality benefits have not yet been proven. Phosphodiesterase inhibitors inhibit the hydrolysis of cyclic guanosine monophosphate, reducing intracellular calcium concentration and effecting smooth muscle relaxation. They are effective when given alone and can augment the efficacy of inhaled NO.
Inhaled NO in concentrations of 20 to 40 ppm can be used to treat PAH. When inhaled, NO diffuses into vascular smooth muscle where it activates guanylate cyclase, increasing intracellular cyclic guanosine monophosphate, which reduces intracellular calcium concentration, resulting in smooth muscle relaxation. After diffusing into the intravascular space, NO binds to hemoglobin, forming nitrosylmethemoglobin, which is rapidly metabolized to methemoglobin and excreted by the kidneys. All NO is rendered inactive in the pulmonary circulation, thereby minimizing systemic effects. Because it is administered via inhalation, NO is preferentially distributed to well-ventilated alveoli, causing vasodilation in these areas. This improves ventilation/perfusion matching and improves oxygenation. NO has been shown to improve oxygenation and lower pulmonary arterial pressure in acute respiratory distress syndrome and in other conditions associated with severe pulmonary hypertension, but it has not been shown to reduce mortality in these situations. Problems associated with NO administration include rebound pulmonary hypertension, platelet inhibition, methemoglobinemia, formation of toxic nitrate metabolites, and the technical requirements for its application.
Prostacyclins are systemic and pulmonary vasodilators that also have antiplatelet activity. The prostacyclins reduce PVR and improve cardiac output and exercise tolerance. However, complications such as worsened intrapulmonary shunting, rebound pulmonary hypertension, and problems associated with the route of administration, such as systemic hypotension, infection, and bronchospasm, can occur. Prostacyclins can be administered by continuous infusion in the short term and the long term (by a pump attached to a permanent indwelling central venous catheter), by inhalation, and by intermittent subcutaneous injection. All prostacyclins demonstrate significant improvements in cardiopulmonary hemodynamics, at least in the short term, but have not yet provided evidence of sustained improvement or a decrease in mortality. Currently used prostacyclins include epoprostenol (Flolan), treprostinil (Remodulin), and iloprost (Ventalis).
Endothelin interacts with two receptors: endothelin A and endothelin B. The endothelin A receptors cause pulmonary vasoconstriction and smooth muscle proliferation, whereas the endothelin B receptors produce vasodilation via enhanced endothelin clearance and increased production of NO and prostacyclin. Endothelin receptor antagonists have been shown to lower PA pressure and PVR and to improve RV function, exercise tolerance, quality of life, and mortality. The only endothelin receptor antagonist currently available for general use in the United States is bosentan (Tracleer).
RV assist devices can be used in severe pulmonary hypertension and right heart failure. Balloon atrial septostomy is an investigational procedure that creates an atrial septal defect and allows right-to-left shunting of blood to decompress the right heart. At the expense of an expected and generally well-tolerated decrease in arterial oxygen saturation, it has been shown to improve exercise tolerance. Currently, this procedure is reserved for treatment of terminal right heart failure and as a bridge to cardiac transplantation. The benefits of extracorporeal membrane oxygenation are well established in children, but this modality has not found widespread use in the adult population. Lung transplantation is the only curative therapy for many types of PAH. Long-term survival is similar with single or bilateral lung transplantation.
The risk of right heart failure is significantly increased in patients with PAH during the perioperative period. Mechanisms for this include increased RV afterload, hypoxemia, hypotension, and inadequate RV preload. Medications for PAH should be continued throughout the perioperative period. Continuous infusions of pulmonary vasodilators should be maintained at their usual doses to prevent rebound pulmonary hypertension. Diuretics may be needed to control edema, but excessive diuresis may dangerously reduce RV preload. Reduction in systemic vascular resistance by inhalational anesthetics or sedatives may be dangerous because of the relatively fixed cardiac output. Hypoxia, hypercarbia, and acidosis must be aggressively controlled because these conditions increase PVR. Maintenance of sinus rhythm is crucial. The atrial “kick” is necessary for adequate right and left ventricular filling.
In a patient with newly diagnosed PAH who is not yet on long-term therapy, administration of sildenafil or L-arginine preoperatively may be helpful. Patients on long-term pulmonary vasodilator therapy must have that therapy continued. Systems for inhalation of NO or prostacyclin should be immediately available. Sedatives should be used with caution because respiratory acidosis may increase PVR. Opioids, propofol, thiopental, and depolarizing or nondepolarizing neuromuscular blockers may all be used safely. Ketamine and etomidate may suppress some mechanisms of pulmonary vasorelaxation and should be avoided. Epidural anesthesia has been used for cesarean delivery and other suitable surgical procedures, but close attention must be paid to intravascular volume and systemic vascular resistance. It is also important to remember that prostacyclins and NO can inhibit platelet function. The level of regional anesthesia should be induced slowly and with invasive hemodynamic monitoring so that adjustment in cardiac variables can be made promptly.
Central venous catheterization is recommended, although care must be taken in the placement of central venous and pulmonary artery catheters because disruption of sinus rhythm by the catheter or wire can be a critical event. Intra-arterial blood pressure monitoring is recommended.
Inhalational anesthetics, neuromuscular blockers and opioids, except those associated with histamine release, can be used for maintenance of anesthesia. Hypotension can be corrected with norepinephrine, phenylephrine, or fluids. A potent pulmonary vasodilator such as milrinone, nitroglycerin, NO, or prostacyclin should be available to treat severe pulmonary hypertension should it develop. During mechanical ventilation, fluid balance and ventilator adjustments must be set to prevent a decrease in venous return.
Patients with PAH are at risk of sudden death in the early postoperative period due to worsening PAH, pulmonary thromboembolism, dysrhythmias, and fluid shifts. These patients must be monitored intensively in the postoperative period to help maintain hemodynamic variables and oxygenation at acceptable levels. Optimal pain control is an essential component of the postoperative care of these patients.
Forceps delivery to decrease patient effort is recommended. Nitroglycerin should be immediately available at the time of uterine involution because the return of uterine blood to the central circulation may be poorly tolerated in the parturient with PAH.
ANAESTHESIA FOR THE PATIENT WITH
PULMONARY HYPERTENSION
ANAESTHESIA TUTORIAL OF THE WEEK 228
JUNE 2011
Dr Sarah Thomas, Senior Anaesthetic Registrar
Royal Hobart Hospital
Correspondence to sarah.thomas@dhhs.tas.gov.au
QUESTIONS
Before continuing, consider the following scenario and question. The answers can be found at the end
of the article, together with an explanation.
You are to anaesthetise a 65-year-old woman for laparoscopic sigmoid colectomy. She has recently
been diagnosed with colorectal carcinoma. The patient has been a heavy smoker in the past and has
severe chronic obstructive pulmonary disease (COPD), with secondary pulmonary hypertension. She
also has essential hypertension. Medications include a beta-blocker, ACE inhibitor, inhaled
steroid/beta-agonist and aspirin.
What are your concerns in anaesthetising this patient?
INTRODUCTION
The disease spectrum of Pulmonary Hypertension (PH) has received greater interest in the past decade,
as specific therapies have been developed and survival has improved. More patients with PH are now
presenting for surgery, and this poses a challenge to the anaesthetist. Knowledge of the underlying
physiology is paramount in preventing the feared complication of right heart failure.
DEFINITION AND CLASSIFICATION
Pulmonary Hypertension is defined as a mean pulmonary artery pressure (PAP) >25mmHg at rest with
a pulmonary capillary wedge pressure <12mmHg. Pulmonary hypertension is considered moderately
severe when mean PAP >35mmHg. Right ventricular failure is unusual unless mean PAP is
>50mmHg.
The World Health Organisation classifies pulmonary hypertension by aetiology into five groups. The
disease, including its classification, was comprehensively reviewed at the 4
th World Symposium on
Pulmonary Hypertension in 2008.
Table 1: Clinical classification of pulmonary hypertension
1 Pulmonary Hypertension (PAH)
2 Pulmonary hypertension owing to left heart disease
3 Pulmonary Hypertension owing to lung disease
4 Chronic thromboembolic pulmonary hypertension (CTEPH)
5 Pulmonary hypertension with unclear multifactorial mechanisms
Group 1 includes the disease idiopathic pulmonary hypertension (formerly known as primary
pulmonary hypertension), as well as PH associated with connective tissue disorders. This group of
diseases share similar pathological findings and clinical appearance. The incidence of idiopathic PH is
higher than previously thought, although remains relatively rare at 15 per million.
Of greater interest to the anaesthetist are the more common forms of PH: those due to left heart disease
(group 2) and those due to lung disease (group 3). Cardiac anaesthetists have long been familiar with
PH due to left heart disease, which often occurs in patients undergoing cardiac surgery. Examples
would include patients with mitral valve disease undergoing valve replacement, or patients with severe
LV failure undergoing coronary bypass surgery.
Non-cardiac anaesthetists are more likely to encounter PH in patients with lung disease. Underlying
diseases include COAD, interstitial lung disease, and sleep disordered breathing. The majority of
patients in this group have modest PH.
PITFALLS IN DIAGNOSIS
Pulmonary hypertension may be suspected after patient assessment based on history, examination,
ECG and chest x-ray. The symptoms of PH are non-specific, and diagnosis can be delayed.
If PH is suspected, transoesophageal echocardiography (TTE) is usually the first investigation
undertaken. TTE utilizes Doppler across a tricuspid regurgitant jet, to estimate pulmonary artery
pressure. This technique has been shown to under or over estimate PAP in up to half of patients at risk
of PH, and therefore as a diagnostic test has limitations in accuracy.
Right heart catheterization is required to confirm the diagnosis. A vasodilator challenge forms part of
this assessment.
UNDERSTANDING THE PHYSIOLOGY
Providing anaesthesia to patients with PH poses some challenges. An underlying knowledge
of the cardiovascular pathophysiology is paramount to providing safe anaesthesia in these
patients.
Right ventricular output is dependent on preload, afterload, contractility and heart rate.
Consideration must be given to optimizing each of these parameters.
Raised pulmonary vascular resistance (PVR) places an additional pressure load on the right
ventricle. The right heart is poorly designed to deal with these increases in afterload. A rise
in PVR and hence right ventricular afterload can put the right heart into failure. Left
ventricular failure can then ensue, due to both reduced volume reaching the left heart, and
septal interdependence.
Factors which can raise PVR include hypoxia, hypercarbia, hypothermia, acidaemia, and
pain. Anaesthetic technique is aimed at preventing these occurrences.
The coronary circulation to the right heart is dependent on perfusion pressure at the aortic
root, which in turn is dependent on cardiac output and systemic vascular resistance (SVR).
SVR must be aggressively defended in order to maintain coronary perfusion to the right heart.
Ischaemia to the right ventricle can put in place a downward spiral of right heart failure, with
ensuing cardiovascular collapse.
ANAESTHETIC TECHNIQUES
Many anaesthetic techniques have been employed in anaesthetising patients with pulmonary
hypertension. The actual technique chosen is probably less important than the manner in
which it is executed.
Extended monitoring will be useful. Invasive blood pressure monitoring is ideal as it will aid
early and aggressive treatment of systemic hypotension. A pulmonary artery catheter can be
useful in monitoring trends in PAP. A rising PAP may indicate a rising PVR or a failing right
ventricle (RV). Transoesophageal echocardiography or other cardiac output monitors can
also be useful.
An effort to obtund the response to laryngoscopy should be made.
A variety of anaesthetic induction drugs have been safely employed in patients with PH. One
technique would be to use a combination of midazolam and fentanyl. Etomidate has been
described as an ideal agent in PH. Propofol and thiopentone have also been used without
problems. Concern has been raised that ketamine may raise PVR, however it too has been
utilized safely in humans with PH.
Non-depolarising and depolarising muscle relaxants can be used safely, and should be
chosen based on airway management issues.
A balanced anaesthetic of volatile agent and opioids can be used as maintenance. All of the
commonly used modern volatile agents have been safely used in PH, and there is no
evidence to recommend one over the other. Nitrous oxide should be used with caution as it
may raise PVR.
A systemic vasoconstrictor such as phenylephrine, noradrenaline or metaraminol should be
on hand to treat reductions in systemic blood pressure. A carefully titrated infusion may be
commenced at induction.
Inotropes can be employed to improve right heart contractility but they are often more
beneficial to the left heart than the right heart. The inodilators such as milrinone and
dobutamine will cause systemic vasodilation and hence reduce coronary perfusion pressure,
which limits their utility.
RV failure and raised PVR can be targeted with inhaled selective pulmonary vasodilators.
Agents such as nitric oxide and prostacyclin are increasingly being employed perioperatively
in these patients.
Neuraxial anaesthesia and analgesia, can be used safely in PH, however the anaesthetist
must be vigilant about the cardiovascular consequences of sympathetic blockade. There are
no alpha-1 adrenoreceptors in the pulmonary circulation, hence it is unlikely that neuraxial
blockade has a direct effect on PVR. Systemic vasodilation however, will reduce aortic
coronary perfusion pressure, as well as venous return to the right heart. A decrease in right
atrial filling can reduce stretch on atrial receptors, resulting in reflex bradycardia. Loss of the
cardio-accelerator fibres at T1-T4 may result in bradycardia and loss of inotropy. Bradycardia
and hypotension can cause right heart failure and can be lethal in patients with PH.
SUMMARY OF ANAESTHETIC TECHNIQUES IN PH
Avoid any stimulus which can increase PVR including: nitrous oxide, adrenaline, dopamine,
protamine, serotonin, thromboxane A2, prostaglandins such as PGF2alpha and PGE2,
hypoxia, hypercarbia, acidosis, PEEP and lung hyperinflation, cold, anxiety and stress.
If PVR is increased it can be reduced by: hypocarbia (via hyperventilation), nitric oxide,
morphine, glyceryl trinitrate, sodium nitroprusside, tolazoline, prostacycline (PGI2),
isoprenaline, and aminophylline.
Aims are to avoid marked decreases in venous return (correct blood and fluid loss quickly),
avoid marked decreases in SVR, avoid drugs which cause myocardial depression, and to
maintain a normal heart rate
A feared complication of pulmonary hypertension is right
heart failure
Understanding the physiology of right ventricular function
and coronary perfusion are important when anaesthetising
patients with pulmonary hypertension
Anaesthetic aims in PH are to avoid increased PVR, to
avoid marked decreases in venous return or SVR, to avoid
myocardial depression and to maintain normal heart rate.
SUMMARY
ANSWERS TO QUESTIONS
Your concerns in anaesthetising this patient may include:
1. The presence of severe systemic disease in a patient undergoing intermediate risk surgery.
Optimisation of the patient’s chronic obstructive pulmonary disease and pulmonary
hypertension is warranted pre-operatively.
2. The cardiovascular and respiratory sequelae of pneumoperitoneum, trendelenburg position,
and potentially prolonged surgery.
3. Anticipation and prevention of perioperative right heart failure in the patient with pulmonary
hypertension.
4. Provision of excellent perioperative pain relief, especially in the patients with lung disease, to
reduce the risk of respiratory complications.
REFERENCES and FURTHER READING
Pritts CD and Pearl RG. Anaesthesia for patients with pulmonary hypertension. Current Opinion in
Anaesthesiology 2010, 23:411-416
Mehta S and Little S. Editorial: Screening for Pulmonary Hypertension in Scleroderma. Journal of
Rheumatology 2006; 33:2 204-206
Manecke GR. Anaesthesia for pulmonary endarterectomy. Semin cardiovasc thorac surgery 18: 236-
242
Slinger PD. Anaesthetic planning for the patient with co-existent disease: the patient with lung disease.
New York Society of Anesthesiologists, 64
th
Annual PGA. Scientific Panel December 2010
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