perioperative care of phaeochromocytoma
TRANSCRIPT
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PERIOPERATIVE CARE OF PHAEOCHROMOCYTOMA
BY DR. CHAMIKA HURUGGAMUWAREGISTRAR IN ANAESTHESIOLOGY
TH KANDY
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CLASSIFICATION
• Phaeochromocytomas are catecholamine-secreting tumours of the adrenal medulla.• Arise from the chromaffin cells of the sympathoadrenal
system.
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AETIOLOGY• The majority develop sporadically, • one-third of cases have specific gene mutations which are
usually inherited in an autosomal-dominant fashion. • These may be associated with other tumours, • multiple endocrine neoplasia 2A and 2B, • Von Hippel–Lindau disease, • succinate dehydrogenase enzyme mutations, and • neurofibromatosis.
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• Almost 100% of patients with MEN2a have or will develop phaeochromocytoma and they are frequently bilateral.
• MEN2b is characterised by medullary carcinoma thyroid, phaeochromocytoma
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INCIDENCE
• European incidence 0.2 per 100 000 people.
• The traditional ‘Rule of 10s’
• 10% of phaeochromocytomas are ‘extra-adrenal’ ,
• 10% are malignant,
• 10% are bilateral,
• 10% are found in normotensive patients, and
• 10% are familial.
• significantly higher proportion of tumours that are malignant (29%), extra-adrenal (24%),2 and/or familial (32%).• Equal in both males and females, • Most prevalent between the third and fifth decades of life.
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• Phaeochromocytomas are highly active tumours secreting adrenaline, noradrenaline and rarely dopamine. • Most tumours predominantly secrete noradrenaline. (Normal
adrenal secretion is 85% adrenaline). • Familial phaeochromocytomas are an exception because they
secrete large amounts of adrenaline
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SYMPTOMS
classic symptom triad• of headache, palpitations, and sweating. • Hypertension is present in around 90% of cases, although it is paroxysmal in 35–50% • Other non-specific presentations include • anxiety, lethargy, nausea,
weight loss, hyperglycaemia, tremor.
• Abdominal pain may result from bowel ischaemia due to excessive vasoconstriction.• Visual disturbance may develop from papilloedema induced by malignant hypertension.
• Half of phaeochromocytomas are diagnosed incidentally on abdominal imaging for an unrelated indication.
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BIOCHEMICAL TESTS• Mixture of norepinephrine, epinephrine, or, more rarely, dopamine• Traditional biochemical diagnosis of phaeochromocytomas relied
upon 24 h collections of urinary catecholamines and vanillylmandelic acid.• Blood sampling for plasma catecholamines.
• The short half-life of plasma catecholamines makes it difficult to differentiate pathological over-production from a transient stress response to venesection
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• Modern techniques measure levels of metanephrine and normetanephrine.• Dopamine-secreting tumours can be identified by measuring
plasma or urinary dopamine and homovanillic acid levels.
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• Both modern and traditional methods have numerous potential causes of false-positive results, • Recent exercise,• Venous sampling in the sitting position, • Dietary factors, • Renal impairment,• Common medications:
• • norepinephrine re-uptake inhibitors (amitriptyline, olanzapine, venlafaxine),• • adrenergic receptor blockers (atenolol, phenoxybenzamine),• • monoamine oxidase inhibitors (moclobemide, phenelzine),• • recreational drugs (cocaine, amphetamine, caffeine),• • sympathomimetics (salbutamol, terbutaline),• • others (paracetamol).
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LOCALISATION
• MRI and CT both provide accurate and consistent identification of the majority of phaeochromocytomas. • MIBG scan. Meta-iodobenzyl guanidine is a
radiopharmaceutical agent which is an analogue of guanethedine, similar in structure to noradrenaline
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PREOPERATIVE PREPARATION
• The objectives of preoperative care include:
• • Arterial pressure control,• • Reversal of chronic circulating volume depletion,• • Heart rate and arrhythmia control,• • Assessment and optimization of myocardial function,• • Reversal of glucose and electrolyte disturbances
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ARTERIAL PRESSURE CONTROL AND VOLUME EXPANSION• Early phaeochromocytoma surgery saw mortality rates of up to 45% • Severe intraoperative hypertension, • Strokes, • Arrhythmias, • Myocardial ischaemia, • Left ventricular failure, and • Refractory hypotension after tumour resection.
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PREOPERATIVE ADRENERGIC BLOCKADE ACHIEVES THE FOLLOWING OBJECTIVES:
• • Lowers blood pressure, • • Increases intravascular volume, • • Reduces the chance of hypertensive crises during induction and
tumour manipulation, • • Allows resensitisation of adrenergic receptors • • Reduces myocardial dysfunction in the perioperative period
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• Commonly used α-blockers include • Phenoxybenzamine and• Doxazosin.
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NON SELECTIVE -PHENOXYBENZAMINE• Non-selective, non-competitive, Long acting α-blocker
Twice daily dosage ----- 10 mg twice daily slowly increased up to 60 -250mg/day.
Disadvantages, undesirable α 2 receptor blockade --------- inhibition of presynaptic NA reuptake ===========tachycardia, ===========persistent α blockade which can be responsible for resistant hypotension after tumour removal• Central α2-blockade results in somnolence, headache, and nasal congestion
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SELECTIVE - DOXAZOSIN
• competitive, selective α1-blocker. • It does not cause tachycardia or sedation and some studies
suggest a reduced incidence of postoperative hypotension, • Its efficacy is currently being investigated by the PRESCRIPT
trial, which randomizes patients to receive either phenoxybenzamine or doxazosin.
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CALCIUM CHANNEL BLOCKERS
• Calcium channel blockers inhibit norepinephrine-induced calcium influx and have been utilized for haemodynamic control before surgery.• Sustained-release nicardipine 30 mg twice daily
• A high sodium diet and fluid intake are also recommended to help restore blood volume
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HEART RATE AND ARRHYTHMIA CONTROL• Tachyarrhythmias - Epinephrine/Dopamine secreting tumours
Secondary to α-blockade
Selective β1 antagonists (Atenolol or Metoprolol ) after complete α-blockade.unopposed α-mediated vasoconstriction that could occur after antagonism of β2-mediated vasodilatation,
precipitate a hypertensive crisis while the negative inotropic effect of β-blockade further
compromises myocardial function)
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ASSESSMENT AND OPTIMIZATION OF MYOCARDIAL FUNCTION
• ECG
• Ventricular hypertrophy, Tachyarrhythmias, Myocardial ischaemia.• Various forms of cardiomyopathy
• Hypertrophic cardiomyopathy• 2D ECHO IS MANDATORY.
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REVERSAL OF GLUCOSE AND ELECTROLYTE DISTURBANCES
• Hyperglycaemia
• Increased glycogenolysis (α1 receptors), • Impaired insulin release (α2 receptors),
• lipolysis (β1 receptors), • Increased glucagon release coupled with peripheral
Insulin resistance (β2 receptors)
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• Electrolyte measurements will identify catecholamine induced renal impairment. • Hypercalcaemia occurs when a neuroendocrine tumour is
associated with a parathyroid adenoma (e.g. as occurs in MEN 2A).
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ASSESSMENT OF ADEQUATE OPTIMIZATION• 1982 Roizen criteria for optimal preoperative control have been
cited:
• • Arterial pressure readings consistently <160/90,• • The Presence of orthostatic hypotension with a decrease in
systolic arterial pressure of at least 15% but not <80 mm Hg,• • An ECG which is free of ST or T wave changes for 2 weeks.
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• contemporary arterial pressure targets are tighter (seated arterial pressure of <130/80mmHg) and orthostatic hypotension is not a necessity. • ST or Twave changes may reflect inverted Takotsubo
cardiomyopathy rather than ischaemia
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INTRAOPERATIVE MANAGEMENT
• Open surgery - large or invasive adrenal masses and most paragangliomas.• Laparoscopic surgery – Transabdominal or Retroperitoneal
approach
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RISK FACTORS FOR INTRAOPERATIVE HAEMODYNAMIC INSTABILITY
• High pre-induction plasma norepinephrine levels, • Large tumour size, • Profound postural drop after commencement of α-blockade, • Pre-induction mean arterial pressure (MAP) above 100 mm
Hg
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THE CHOSEN ANAESTHETIC TECHNIQUE SHOULD:
• • Avoid drug-induced catecholamine release,• • Avoid catecholamine release induced by anaesthetic or surgical
manoeuvres,• • minimize haemodynamic responses to tumour handling,• • treat episodes of hypotension, particularly after tumour
devascularization.
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AVOIDING DRUG-INDUCED CATECHOLAMINE RELEASE• desflurane ketamine morphine
pethidine atracurium pancuronium ephedrine droperidol metoclopramide cocaine • succinylcholine
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AVOIDING CATECHOLAMINE RELEASE INDUCED BY ANAESTHETICOR SURGICAL MANOEUVRES• Tumour handling• Tracheal intubation and the raised intra-abdominal pressure
associated with capnoperitoneum or coughing
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Magnesium sulphate
• Inhibits adrenal catecholamine release • Reduces α-adrenergic receptor sensitivity to catecholamines• Dilates arteriolar vessels, • Antiarrhythmic effects via antagonism of L-type calcium channels
RemifentanilBlunt Haemodynamic responses to intubation or pain
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Dexmedetomidine• Centrally acting selective α2-receptor agonist with sedative and
analgesic properties.• Adjuvant to volatile or propofol anaesthesia• Central sympatholytic effects result in substantial reductions in
plasma norepinephrine levels
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MINIMIZING HAEMODYNAMIC RESPONSES TO TUMOUR
HANDLING• Profound hypertension, bradycardia (with norepinephrine),• Tachyarrhythmias (with epinephrine)
• Hypertensive crises are generally managed with a vasodilator, while tachyarrhythmias, including the reflex tachycardia seen with the use of many vasodilators, are controlled with β-blockers
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• Phentolamine• Sodium nitroprusside and Glyceryl trinitrate• Nicardipine• Esmolol
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TREATING HYPOTENSION AFTER TUMOUR DEVASCULARIZATION• Final ligation of the tumour’s venous supply is associated with a sudden
drop in plasma catecholamine concentrations, often precipitating rapid refractory hypotension. • Down-regulation of α-receptors, • Suppression of the contralateral adrenal medulla, • persistence of pre-operative adrenergic-receptor blockade, • Relative hypovolaemia and • catecholamine-induced cardiomyopathy.
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• In the first instance, hypotensive agents should be stopped and fluid balance optimized taking into account the possibility of ongoing postoperative haemorrhage, myocardial dysfunction, or both. • Norepinephrine can initially be used to increase peripheral vascular
resistance and vasopressin should be considered if hypotension is refractory.
• Vasopressin
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MONITORING
• Standard AAGBI monitoring• Invasive arterial monitoring• CVP• Cardiac output monitoring
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POSTOPERATIVE CARE
• Managed post operatively in an ITU/HDU• Extubation at the end of surgery if uncomplicated intraop.• All patients should receive invasive arterial pressure monitoring in a high
dependency environment for at least 24 h after the procedure• steroid supplementation if bilateral adrenalectomy is carried out or if
hypoadrenalism is suspected• Post operative pain control depends on the type of incision. Epidural analgesia
provides good post operative pain relief and may be supplemented by regular oral medications
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Hypertension• pain, • co-existing essential hypertension, • urinary retention, or • fluid overload. • Inadvertent ligation of the renal artery precipitates hyper-reninism, which
may lead to delayed hypertension. • Incomplete tumour resection
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• Hypoglycaemia
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INCIDENTAL PRESENTATION DURING SURGERY• Presenting features include hypertension (by far the most• common presentation during incidental surgery), • Tachyarrhythmias,• and cardiac failure associated with hypotension and pulmonary oedema• Surgery should be terminated as soon as is feasible and thus, unlike planned
phaeochromocytoma surgery, continued catecholamine surges may persist after operation.• Excessive intra- and postoperative vascular spasm may result in myocardial or
cerebral infarction, acute kidney injury, and/or mesenteric ischaemia.
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