MANAGEMENT OF DIFFICULT MANAGEMENT OF DIFFICULT ORTHOSTATIC HYPOTENSIONORTHOSTATIC HYPOTENSION

COLIN A J FARQUHARSONCOLIN A J FARQUHARSON MBChB FRCP FESCMBChB FRCP FESC

Dept of CardiologyDept of CardiologyRoyal Darwin HospitalRoyal Darwin Hospital

18 December 201218 December 2012

Therapy for Orthostatic Therapy for Orthostatic Hypotension – General AimsHypotension – General Aims

• Comprises both pharmacological and non-pharmacological measures

• Therapies must balance an increase in standing BP vs prevention of unwanted supine hypertension

• Doses of therapies used for efficacy may bring significant unwanted side-effects

Orthostatic Hypotension (OH)Orthostatic Hypotension (OH)Defined as BP drop on standing of >20/10mmHg

Occurs within 3 minutes of standing

Why? When rising from lying to standing position, 300 to 800 ml of blood pools in legs

Physiological response to this:

• Lower extremity muscle contraction compresses veins

• Autonomic response

Baroreceptors in aorta and carotids sense BP change

Sympathetic nervous system response

Increases vascular tone

Increases heart rate and cardiac contractility

ORTHOSTATIC HYPOTENSION OCCURS WHEN THESE RESPONSES ORTHOSTATIC HYPOTENSION OCCURS WHEN THESE RESPONSES ARE DYSFUNCTIONALARE DYSFUNCTIONAL

OH causes brain hypoperfusion

Orthostatic Hypotension - CausesOrthostatic Hypotension - CausesCARDIOGENIC CAUSES

1. Myocardial Infarction

2. Arrhythmia

3. Aortic stenosis

4. Myocarditis

5. Pericarditis

6. Pathological bradycardia

HYPOVOLAEMIC CAUSES

1.Haemorrhage

2.Anaemia / dehydration

3.Burn injury

4.Addison’s / DI

5.Straining

- Heavy lifting

- Urinating (Micturition syncope)

Orthostatic Hypotension - causesOrthostatic Hypotension - causesDRUGS

• Methyldopa

• MAO Inhibitors

• Tricyclic antidepressants

• Phenothiazines

• Clonidine / alpha blockers

• Beta blockers

• Vasodilator medications e.g. ACEI / CCBD / Nitrates

• Diuretics

• Quinidine / quinine

• Levodopa

• Barbiturates

• Opiates (e.g. Morphine)

• Vincristine

• Insulin (vasodilator)

• Sildenafil (Viagra)

Orthostatic Hypotension - causesOrthostatic Hypotension - causesNEUROGENIC CAUSES

• Diabetic Neuropathy

• Spinal cord injury

• Guillain-Barre syndrome

• Parkinsonism / MSA

• Tabes dorsalis

• Amyloidosis

• Alcohol abuse

• Vitamin B12 deficiency

• Syringomyelia

• Post-sympathectomy

• HIV

• Idiopathic orthostatic hypotension

• Carotid sinus hypersensitivity

Orthostatic Hypotension - causesOrthostatic Hypotension - causesVENOUS POOLING

• Large leg varices

• Prolonged bed rest

• Strenuous exercise

• Fever

• Sepsis

• Heat exposure

• Postprandial shunting

• Alcohol (acute)

MISCELLANEOUS

• Ageing

• Hypokalaemia

OH and autonomic dysfunctionOH and autonomic dysfunctionDiagnosis can be made clinically using part of “Ewing’s

Battery” – can easily be used in ward setting

• Orthostatic Blood Pressure and Pulse Response - Supine BP and pulse after 3-5 minutes - Standing BP and pulse after 3-5 minutes - Abnormal if BP drops >20/10mmHg

• Response to 15 second Valsalva manoeuvre- Normally pressure falls, then rises over baseline - Abnormal if pressure does not overshoot baseline

• Pulse variation on deep breathing (sinus arrhythmia) - Normal response

Tachycardia on inspiration Bradycardia on expiration

- Abnormal if <9 beat/min difference during cycle

Orthostatic Hypotension - diagnosisOrthostatic Hypotension - diagnosisOther investigative modalities can be used to objectively assess potential imbalance in sympathetic / parasympathetic nervous system and autonomic dysfunction e.g.

• ECG Heart Rate Variability analysis• ECG QT Dispersion• MSNA• IV vasodilator baroreceptor sensitivity studies

Most techniques however are too time / labour-intensive outwith a research / teaching hospital framework

Tilt-table testing is however good for screening for vagally-mediated vasodepressor syncope

Orthostatic Hypotension – general Orthostatic Hypotension – general managementmanagement

• MOST CASES DUE TO HYPOVOLAEMIA / DRUGS- Consider intravascular volume

replacement (i.e. IV Fluids / Packed RBCs) - Stop hypotension-inducing drugs in first

instance

• Consider causes above and investigate / treat appropriately if possible

• PACING ONLY HELPS IF INITIAL STIMULUS FOR COLLAPSE IS PATHOLOGICAL BRADYCARDIA

Non-Pharmacological Measures for Non-Pharmacological Measures for Dysautonomic Orthostatic Dysautonomic Orthostatic

HypotensionHypotension• Increase water intake (high volume bolus –

500ml at time minimum)

• Eat small but frequent meals (large meal can drop BP by approx 20-30mmHg)

• Regular lower-limb exercises

• Compression stockings (MAST trousers in extreme circumstances!)

• Head of bed elevation 5-20°

Measures for Orthostatic Measures for Orthostatic Hypotension – MAST trousersHypotension – MAST trousers

FLUID THERAPY AS FLUID THERAPY AS TREATMENT…TREATMENT…

Water and BP in Autonomic Failure

Jens Jordan et al. Circulation 2000;101:504

Effect of Nicotinic Blockade (Trimethaphan) Effect of Nicotinic Blockade (Trimethaphan) on Pressor Action of Wateron Pressor Action of Water

05

1015202530354045

No Trim Trim

BP RisemmHg change

Autonomic Function Necessary for Pressor Action

500 ml Oral vs Intravenous Fluid500 ml Oral vs Intravenous Fluid

05

1015202530354045

Oral water IV Saline

Systolic BP rise

The oral route is key to water’s pressor effect –why?

mmHg

Does Oral Water Change Does Oral Water Change Sympathetic Activity?Sympathetic Activity?

36373839404142434445

Before H2O After H2O

MSNAbursts/min

Water increases sympathetic activity

Pharmacological Measures for Pharmacological Measures for Orthostatic HypotensionOrthostatic Hypotension

• Fludrocortisone +/- Salt supplements (+/- NSAID use)

• Midodrine

• Caffeine +/- Ergotamine

• Erythropoetin (works best if comorbid anaemia)

• Ocreotide

• ? Pyridostigmine

• ? Fluoxetine

• ?? Beta-blockers ?? Vasopressin analogues

• ? Continuous SC Norepinephrine infusion via pump

Pharmacological Measures for Pharmacological Measures for Orthostatic HypotensionOrthostatic Hypotension

• Fludrocortisone +/- Salt supplements (+/- NSAID use)

- all work by expanding intravascular fluid volume

- risk of volume overload / hypokalaemia / low Mg

- s/e include headache / weight gain / oedema / supine hypertension

• Midodrine

- vasoconstrictor with mainly alpha-agonist activity

- s/e include pupillary dilatation / paraesthesia / piloerection / pruritis

- also causes supine hypertension

Pharmacological Measures for Pharmacological Measures for Orthostatic HypotensionOrthostatic Hypotension

•Caffeine +/- Ergotamine- caffeine increases renin / Ad / NAd levels

- ergotamine is venoconstrictor

- use limited by many side-effects

• Erythropoetin - effective in autonomic failure related to decreased RBC mass or anaemia

- often causes increased appetite / well-being

• Ocreotide- SRIH analogue

- works synergistically with midodrine to reduce drops in BP related to food ingestion

Pharmacological Measures for Pharmacological Measures for Orthostatic HypotensionOrthostatic Hypotension

• Pyridostigmine- acetylcholinesterase inhibitor – increases ganglionic catecholamine transmission

• Fluoxetine- SSRI – enhances baroreflex control of SNS in some patients with autonomic failure

• Beta-blockers- may block SNS-mediated initial stimulus for low BP in some patients (but make it worse in others!!)

• Vasopressin analogues- usefulness limited by water intoxication

Therapy of Severe Dysautonomic Therapy of Severe Dysautonomic Orthostatic Hypotension - summaryOrthostatic Hypotension - summary

FIRST LINE:1. Water (+40 mmHg!) – not alcohol!2. Small amounts of Food (-30mmHg!)

SECOND LINE:1. Physical Counter-Manoeuvres 2. Exercise (esp. lower limb)

THIRD LINE:1. Fludrocortisone + Salt + NSAIDS2. Pressor Drugs (e.g. midodrine)3. Consider other investigational

drugs (off-license)

…….take it. .take it. Yogi BerraYogi Berra

When you come to a fork in the When you come to a fork in the road…road…