Anesthetic management Anesthetic management in Conn’s Syndrome and in Conn’s Syndrome and

PheochromocytomaPheochromocytoma

- Dr. Shashikant . Y- Dr. Shashikant . Y

Conn’s SyndromeConn’s Syndrome

Conn’s Syndrome is a primary Conn’s Syndrome is a primary hyperaldosteronism state.hyperaldosteronism state.

There is excess secretion of aldosterone There is excess secretion of aldosterone from a functional tumour (aldosteronoma) from a functional tumour (aldosteronoma) independent of physiological stimulus.independent of physiological stimulus.

More common in women. Rare in childrenMore common in women. Rare in children May be assoc. with pheochromocytoma, May be assoc. with pheochromocytoma,

acromegaly or primary acromegaly or primary hyperparathyroidism.hyperparathyroidism.

Secondary hyperaldosteronism is present when Secondary hyperaldosteronism is present when increased circulating serum concentrations of increased circulating serum concentrations of renin, as in renovascular hypertension, stimulate renin, as in renovascular hypertension, stimulate the release of aldosterone.the release of aldosterone.

Conn’s syndrome is assoc. with hypertension, Conn’s syndrome is assoc. with hypertension, whereas aldosteronism in Bartter’s syndrome is whereas aldosteronism in Bartter’s syndrome is not accompanied by systemic hypertension.not accompanied by systemic hypertension.

The prevalence of primary aldosteronism in The prevalence of primary aldosteronism in patients with essential hypertension appears to patients with essential hypertension appears to be < 1%be < 1%

Signs and SymptomsSigns and Symptoms

Nonspecific signs and symptoms; some Nonspecific signs and symptoms; some asymptomatic.asymptomatic.

Headache due to hypertensionHeadache due to hypertension PolyuriaPolyuria NocturiaNocturia Skeletal muscle crampsSkeletal muscle cramps Skeletal muscle weaknessSkeletal muscle weakness

Hypertension is usually more of a Diastolic Hypertension is usually more of a Diastolic hypertension (DBP often >100-125 mmHg)hypertension (DBP often >100-125 mmHg)

Its due to aldosterone induced Na retention and Its due to aldosterone induced Na retention and resulting resulting ↑ed ECF volume↑ed ECF volume

Aldosterone Aldosterone ↠ renal excretion of K ↠ ↠ renal excretion of K ↠ hypokalemic metabolic alkalosis.hypokalemic metabolic alkalosis.

↑↑ed Urinary excretion of K >30 mEq daily in the ed Urinary excretion of K >30 mEq daily in the presence of hypokalemia suggests primary presence of hypokalemia suggests primary aldosteronism. aldosteronism.

Hypokalemic nephropathy can result in Hypokalemic nephropathy can result in polyuria and inability to concentrate urine polyuria and inability to concentrate urine optimally.optimally.

Diagnosis and TreatmentDiagnosis and Treatment Spontaneous hypokalemia with systemic hypertension.Spontaneous hypokalemia with systemic hypertension. Plasma Renin activityPlasma Renin activity

Reduced Reduced ↠ prim. aldosteronism↠ prim. aldosteronism Increased ↠ secondary aldosteronismIncreased ↠ secondary aldosteronism

A ratio of serum aldosterone (in ng/dL) to plasma A ratio of serum aldosterone (in ng/dL) to plasma renin activity (in ng/mL per hour) > 30 and an renin activity (in ng/mL per hour) > 30 and an absolute level of aldosterone >15 ng/dL suggest absolute level of aldosterone >15 ng/dL suggest primary aldosteronism.primary aldosteronism.

Failure to suppress plasma aldosterone (to 5 Failure to suppress plasma aldosterone (to 5 ng/dL after 500 mL/h of normal saline x 4 h)ng/dL after 500 mL/h of normal saline x 4 h)

A syndrome with all features of A syndrome with all features of hyperaldosteronism ↠ may result from chr. hyperaldosteronism ↠ may result from chr. Ingestion of Licorice. Ingestion of Licorice.

Initial treatment Initial treatment ↠ supplemental K, ↠ supplemental K, competitive aldosterone antagonist – competitive aldosterone antagonist – SpirinolactoneSpirinolactone

Anti hypertensive medicationsAnti hypertensive medications Drug induced diuresis ↠ accentuation Drug induced diuresis ↠ accentuation

of hypokalemia ↠ use K sparing of hypokalemia ↠ use K sparing diuretic such as triamterene diuretic such as triamterene

Definitive treatment ↠ surgical Definitive treatment ↠ surgical excision.excision.

Anesthetic managementAnesthetic management

Aim – good preoperative control of hypertension Aim – good preoperative control of hypertension and correction of hypokalemiaand correction of hypokalemia

Hypokalemia can modify responses to NDMR.Hypokalemia can modify responses to NDMR. All routine monitoring like ECG, pulse oximetry, All routine monitoring like ECG, pulse oximetry,

NIBP, temp. monitoring. In addition invasive NIBP, temp. monitoring. In addition invasive arterial BP is recommended before induction.arterial BP is recommended before induction.

Inhaled or IV agents can be used.Inhaled or IV agents can be used. Use of sevoflurane questionable ; if hypokalemic Use of sevoflurane questionable ; if hypokalemic

nephropathy or polyuria exists preoperatively.nephropathy or polyuria exists preoperatively.

CVP and PA catheter CVP and PA catheter ↠ for adequate evaluation ↠ for adequate evaluation of the intravascular fluid volume and of the intravascular fluid volume and response to IV fluids. response to IV fluids.

Aggressive preoperative preparation can Aggressive preoperative preparation can convert excessive intravascular fluid volume convert excessive intravascular fluid volume status of these patients to unexpected status of these patients to unexpected hypovolemia ↠ manifesting as hypotension.hypovolemia ↠ manifesting as hypotension.

Orthostatic hypotension should be looked for.Orthostatic hypotension should be looked for. ABG intraoperatively.ABG intraoperatively. Exogenous cortisol.Exogenous cortisol.

PheochromocytomaPheochromocytoma

Catecholamine secreting tumours originating Catecholamine secreting tumours originating from adrenal medulla or in chromaffin tissues from adrenal medulla or in chromaffin tissues along the paravertebral sympathetic chain, from along the paravertebral sympathetic chain, from pelvis to base of skull. pelvis to base of skull.

Conventionally adrenal tumours are termed Conventionally adrenal tumours are termed ‘pheochromocytomas’ and extra-adrenal ones ‘pheochromocytomas’ and extra-adrenal ones ‘paraganglionomas’‘paraganglionomas’

> 95% found in abdominal cavity and about 90% > 95% found in abdominal cavity and about 90% originate in adrenal medulla.originate in adrenal medulla.

Rule of TenRule of Ten

10% malignant10% malignant 10% extra-adrenal sites10% extra-adrenal sites 10% Bilateral10% Bilateral 10 % familial 10 % familial 10 % Asymptomatic10 % Asymptomatic

Occurs in the age Occurs in the age group of 30- 50 yrs. group of 30- 50 yrs. About 1/3About 1/3rdrd in children in children usually males.usually males.

They may be a part of They may be a part of polyglandular polyglandular syndrome referred to syndrome referred to as MEN IIA or IIB.as MEN IIA or IIB.

MEN IIAMEN IIA MEN IIBMEN IIBMedullary Medullary carcinoma of carcinoma of thyroidthyroid

Medullary Medullary carcinoma of carcinoma of thyroidthyroid

PheochromocytoPheochromocytomama

PheochromocytoPheochromocytomama

Parathyroid Parathyroid hyperplasiahyperplasia

Mucosal Mucosal neuromasneuromas

Marfanoid habitusMarfanoid habitus

Von Hippel –Von Hippel –lindau diseaselindau disease

Although fewer than 0.1% of patients of Although fewer than 0.1% of patients of systemic hypertension have systemic hypertension have pheochromocytoma, nearly 50% of deaths pheochromocytoma, nearly 50% of deaths in pts. with unsuspected in pts. with unsuspected pheochromocytoma occur during pheochromocytoma occur during unrelated anesthesia and surgery or unrelated anesthesia and surgery or parturition.parturition.

Signs and symptomsSigns and symptoms Pheochromocytomas usually present with the triad of

headache, sweating and palpitations, singly or in combination.

The sensitivity of diagnosing a pheochromocytoma in a hypertensive patient with all the three symptoms is more than 90%.

Very often, symptoms of co existing disease are predominant.

Hypertension in phaeochromocytoma may be paroxysmal [48%, suggestive of predominant epinephrine(E) or mixed nor epinephrine (NE)-E tumour], or sustained (29%, suggestive of a NE tumour). Nearly 13% patients are normotensive.

No correlation has been observed between plasma levels of catecholamines and hypertension. Patients with sustained high catecholamine levels may be normotensive;

Patients with recurrent crises may have normal circulating catecholamines.

The presynaptic sympathetic nerve terminals are loaded with NE and E vesicles which get discharged across the synaptic cleft following even minimal stimulation, causing a severe haemodynamic response with little or no increase in circulating catecholamines.

On the other hand, sustained levels of NE and E are responsible for chronic signs of vasoconstriction, haemoconcentration, cardiomyopathy and myocarditis.

Neuropeptide Y may potentiate NE action and be responsible for alpha blockade-resistant phaeochromocytoma.

In view of the diverse and unpredictable nature of symptoms and the potentially lethal nature of the disease, it is important to have a high index of suspicion for ‘high risk’ individuals:

Patients with episodic headache, tachycardia and sweating, with or without hypertension

Previous unexplained adverse cardiovascular response to surgery/parturition/straining.

Adverse cardiovascular response to histamine, succinylcholine, metoclopramide.

Patients with adrenal ‘incidentaloma’ and family h/o of pheochromocytoma or MEN II syndrome.

Hyperglycemia reflects a predominance of Hyperglycemia reflects a predominance of alpha adrenergic activity (inhibitn of insulin alpha adrenergic activity (inhibitn of insulin release, glycogenolysis)release, glycogenolysis)

Enhanced coagulation may accompany Enhanced coagulation may accompany chronic catecholamine excess.chronic catecholamine excess.

Orthostatic hypotension – reflects Orthostatic hypotension – reflects decreases in intravasc. Fluid volume decreases in intravasc. Fluid volume assoc. with sustained systemic HTN. assoc. with sustained systemic HTN.

Haematocrit > 45% - hypovolemia caused Haematocrit > 45% - hypovolemia caused by chronic increased in systemic BPby chronic increased in systemic BP

DiagnosisDiagnosis

Biochemical Accurate tools like High Performance Liquid

Chromatography (HPLC) are now available for plasma catecholamine estimation. However plasma catecholamines suffer from several drawbacks. Their sensitivity is low (84%) as discussed earlier.

Measurement of free norepinephrine in a 24 hr urine collection provides a more sensitive index than the metabolites (VMA,metanephrines,normetanephrines)

Clonidine suppression test

Radiological localization Both CT and MRI have high sensitivity and

specificity and can detect tumours <2 cm in size.

131 Meta Iodo Benzyl Guanidine (MIBG) scan is performed routinely on all pheochromocytoma patients to detect multicentricity and metastatic disease.

The newer modalities are PET scan using 11C hydroxyephedrine and octreotide scans for paragangliomas.

ECG – for LVH and non specific T wave ECG – for LVH and non specific T wave changes.changes.

Chest radiograph may reveal Chest radiograph may reveal cardiomegaly.cardiomegaly.

TreatmentTreatment

Surgical excision – definitive treatmentSurgical excision – definitive treatment Before Surgery , its important to establish Before Surgery , its important to establish

alpha blockadealpha blockade To stabilize systemic BPTo stabilize systemic BP To expand intravascular volumeTo expand intravascular volume To normalize myocardial performanceTo normalize myocardial performance

Most studies recommend patients receive Most studies recommend patients receive alpha blockers usually phenoxybenzamine alpha blockers usually phenoxybenzamine 10-20 mg PO twice daily.10-20 mg PO twice daily.

Most patients require 80-200 mg /dayMost patients require 80-200 mg /day

αα adrenergic blockade – attenuates or prevents adrenergic blockade – attenuates or prevents catecholamine induced HTN.catecholamine induced HTN.

Return to normotension facilitates increase in Return to normotension facilitates increase in intravascular fluid volume, as reflected by intravascular fluid volume, as reflected by decreases in hematocrit.decreases in hematocrit.

Persistence of tachycardia or cardiac Persistence of tachycardia or cardiac dysrythmias despite presence of dysrythmias despite presence of αα blockade – blockade – indication for indication for ββ blockade. blockade.

Propranolol 40mg PO twice daily can be used.Propranolol 40mg PO twice daily can be used. Avoided in pts. with cardiomyopathy – may Avoided in pts. with cardiomyopathy – may

precipitate heart failure.precipitate heart failure. αα-methyltyrosine inhibits enzyme tryrosine -methyltyrosine inhibits enzyme tryrosine

hydroxylase – rate limiting step in catecholamine hydroxylase – rate limiting step in catecholamine biosynthesis.biosynthesis.

To date, there is no study for optimal preop To date, there is no study for optimal preop duration of phenoxybenzamine therapy. Most duration of phenoxybenzamine therapy. Most pts. require treatment for 10-14 days.pts. require treatment for 10-14 days.

The following criteria for an optimal pre-op The following criteria for an optimal pre-op condition are recommended:condition are recommended: No “ in hospital” BP reading > 160/90 mm Hg should No “ in hospital” BP reading > 160/90 mm Hg should

be evident for 24hrs before Sx.be evident for 24hrs before Sx. Orthostatic hypotension with readings above 80/45 Orthostatic hypotension with readings above 80/45

mm Hg should be present.mm Hg should be present. ECG should be free of ST-T abn. for atleast a week. If ECG should be free of ST-T abn. for atleast a week. If

abn. 2D-ECHO should reveal no evidence of RWMA abn. 2D-ECHO should reveal no evidence of RWMA or Global myocardial abn. that cannot be attributed to or Global myocardial abn. that cannot be attributed to a permanent deficit.a permanent deficit.

The patient should have no more than 1 VPC every The patient should have no more than 1 VPC every 5mins. 5mins.

Drugs used in pheochromocytomaDrugs used in pheochromocytoma

Alpha blockers – Phentolamine, prazosin, Alpha blockers – Phentolamine, prazosin, phenoxybenzaminephenoxybenzamine

Beta blockers – propanolol, esmolol, Beta blockers – propanolol, esmolol, atenololatenolol

LabetalolLabetalol Vasodilators – Nitroprusside, magnesium Vasodilators – Nitroprusside, magnesium

sulfatesulfate Ca channel blockers –Ca channel blockers –

Diltiazem ,nicardipineDiltiazem ,nicardipine

Anesthetic ManagementAnesthetic Management

Preoperative preparationPreoperative preparation The aim of pre operative preparation is to provide The aim of pre operative preparation is to provide

symptom control and cardiovascular stability.symptom control and cardiovascular stability. Continuation of Continuation of αα blockers until the day of Sx is blockers until the day of Sx is

recommended.recommended. ββ blockers should also be continued until the day of blockers should also be continued until the day of

Sx.Sx. The times of significant intraoperative hazard to the The times of significant intraoperative hazard to the

patients.patients.• During tracheal intubationDuring tracheal intubation• During manipulation of tumourDuring manipulation of tumour• After ligation of tumour’s venous drainageAfter ligation of tumour’s venous drainage

PremedicationPremedication Reassurance and familiarity with the patient

are the best premedicants. Benzodiazepines can be given at night.

Scopolamine can also be with BZDs If B/L adrenalectomy is anticipated,

supplemental cortisol T/t may be instituted at the same time as preoperative medication.

Sites for arterial and CVP cannulation are inspected and the patient is explained and prepared mentally about insertion of cannulae under local anesthesia.

Intraoperative ManagementIntraoperative Management Anesthetic, vasopressors and vasodilators Anesthetic, vasopressors and vasodilators

should be all prepared and available before should be all prepared and available before induction of anesthesia.induction of anesthesia.

Routine Monitoring + invasive BP recording Routine Monitoring + invasive BP recording should be available, placement of a PA should be available, placement of a PA catheter is useful for monitoring of catheter is useful for monitoring of intravascular fluid volume.intravascular fluid volume.

Induction: often with iv administratn of Induction: often with iv administratn of barbiturate, etomidate or propofol. barbiturate, etomidate or propofol.

Depth of anesthesia increased with nitrous Depth of anesthesia increased with nitrous oxide + volatile anesthetics.oxide + volatile anesthetics.

Choice of volatiles based on ability of drug to Choice of volatiles based on ability of drug to decrease sympath. Nervous system activity.decrease sympath. Nervous system activity.

Isoflurane is very widely used. However sevo Isoflurane is very widely used. However sevo and des also tried.and des also tried.

Avoid histamine releasing NDMR Avoid histamine releasing NDMR Scoline is avoided.Scoline is avoided. Laryngoscopy and intubation response can be Laryngoscopy and intubation response can be

minimized with IV lignocaine 1-2 mg/kg IV. minimized with IV lignocaine 1-2 mg/kg IV. Adequate depth of anesthesia is ensured before Adequate depth of anesthesia is ensured before

attempting intubation.attempting intubation.

Maintenance of AnesthesiaMaintenance of Anesthesia Nitrous oxide + volatile anestheticsNitrous oxide + volatile anesthetics Continous iv infusion of nitroprusside may be Continous iv infusion of nitroprusside may be

necessary, if HTN persists despite delivery of necessary, if HTN persists despite delivery of maximal conc. of volatile anesthetic drugs maximal conc. of volatile anesthetic drugs (1.5- 2.0 MAC)(1.5- 2.0 MAC)

Reflex tachycardia accompanying SNP can Reflex tachycardia accompanying SNP can be treated with continuous infusion of be treated with continuous infusion of esmolol.esmolol.

Once veins draining tumour are ligated, Once veins draining tumour are ligated, hypotension can occur hypotension can occur

Once veins draining tumour are ligated, hypotension can Once veins draining tumour are ligated, hypotension can occur. occur.

Hypotension is multifactorial in origin- residual a Hypotension is multifactorial in origin- residual a blockade, suppression of contralateral adrenal function, blockade, suppression of contralateral adrenal function, desensitization of a2 receptors, loss of elastance of desensitization of a2 receptors, loss of elastance of arterioles and volume loss have all been implicatedarterioles and volume loss have all been implicated.

Treated byTreated by Decreasing the conc. of volatilesDecreasing the conc. of volatiles Rapid IV infusions of crystalloids and/or colloidsRapid IV infusions of crystalloids and/or colloids Rarely , a continuous infusion of phenylephrine or Rarely , a continuous infusion of phenylephrine or

norepinephrine is required until SVR adapts to decreased levels norepinephrine is required until SVR adapts to decreased levels of endogenous alpha adrenergic stimulation.of endogenous alpha adrenergic stimulation.

Monitoring ABG, blood glucose conc. and electrolytes is Monitoring ABG, blood glucose conc. and electrolytes is recommended intraoperatively.recommended intraoperatively.

Points to consider during laparoscopic excision of phaeochromocytoma

Positioning: Phaeochromocytomas can be excised through the

transperitoneal (supine or lateral) or the retroperitoneoscopic (lateral or prone) techniques.

Whatever the position, IV access should be satisfactory. The internal jugular catheter may need to be placed on the ipsilateral side to avoid kinking and allow free access to the central circulation for administration of vaso active drugs.

For posterior retroperitoneoscopic procedures, the prone position is necessary. The endotracheal tube should shoud be fixed well. The eyes and pressure points should be padded and protected. The abdomen should be free to move and airway pressures kept under constant check.

Intra operative haemodynamic events Pneumoperitoneum- increases systemic vascular

resistance, mean arterial pressure and induce catecholamine release, all of which could theoretically be exaggerated in the presence of pheochromocytoma.

Absorption of increasing amounts of CO2 from the retroperitoneal/ peritoneal space and its consequences has also been a contentious issue . However, these fears are largely unfounded, especially if insufflation pressures are kept at 8-12 mm Hg.

Tumour manipulation during laparoscopic surgery is invariably associated with short lived but steep rises in blood pressure.

Postoperative managementPostoperative management Invasive monitoring continued in Invasive monitoring continued in

postoperative period.postoperative period. Persistent Hypotension refractory to volume Persistent Hypotension refractory to volume

replacement is a common complication.replacement is a common complication. Persistent hypertensionPersistent hypertension Hypoglycemia should be looked for.Hypoglycemia should be looked for. Neuraxial opioids for postop pain relief.Neuraxial opioids for postop pain relief.

Regional AnesthesiaRegional Anesthesia Can be used for excision of Can be used for excision of

pheochromocytomapheochromocytoma Despite sympathetic blockade, post synaptic Despite sympathetic blockade, post synaptic

alpha receptors still respond to direct effects alpha receptors still respond to direct effects of sudden increase in catecholaminesof sudden increase in catecholamines

Disadvantages Disadvantages • Absence of sympathetic activity, if hypotension Absence of sympathetic activity, if hypotension

follows vascular isolation of tumourfollows vascular isolation of tumour• Also ability to maintain spontaneous ventilation Also ability to maintain spontaneous ventilation

during intra-abdominal manipulation and retraction.during intra-abdominal manipulation and retraction. Regional anesthesia is practical if only in Regional anesthesia is practical if only in

supine position.supine position.

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