University College of Medical Sciences & GTB Hospital, Delhi INDUCED HYPOTENSION Dr. Emeni Ophrii University College of Medical Sciences & GTB Hospital, Delhi

Induced Hypotension Definition and objectives Historical background Purpose Indications Techniques with physiological basis, drugs Contraindications Limitations Post-operative care Specific applications Current status

Definition A technique that lowers blood pressure (BP) to reduce blood loss and the need for transfusion during surgery and to improve the quality of surgical field Also known as deliberate hypotension / controlled hypotension / hypotensive anaesthesia

Objectives Fall in systolic BP to 80-90 mmHg Fall in mean arterial pressure(MAP) to 50-65 mmHg Fall in 30% of MAP in hypertensive patients In majority of cases, optimum operating conditions are the goal, not a specific pressure → good communication between anaesthetist and surgeon is essential

Historical background Harvey Cushing proposed in 1917 Gardner practised first in 1946 Griffith and Gillies used high spinal analgesia Enderby used ganglionic blockers Trimetaphan Sodium nitroprusside(SNP)-1962 Halothane β-adrenergic blockers Nitroglycerine and labetalol-1970

Purpose Less infection transmission Reduction in blood loss Haemodynamic and metabolic stability Less transfusion requirements Less infection transmission Improvement of surgical field Improved visualization → better and faster surgery Facilitation of vascular surgery Prevention of progressive stretching of thin walls of vessels → easier suturing and clipping (aortic surgery, AVM, intracranial aneurysm clipping )

Indications Neurosurgery (AVM, intracranial aneurysm, vascular tumours, trans-sphenoidal hypophysectomy) Major orthopaedic surgery (spinal surgery, shoulder/hip arthroplasty) ENT surgery (middle ear surgery) Head and neck (faciomaxillary tumours, block dissection of neck, laryngectomy)

Indications… Ophthalmic surgery (intraocular tumours, vitrectomy, orbital surgery) Pelvic (Major gynaecological or rectal surgery) Plastic and reconstructive surgery Jehovah’s witness

Techniques Physical measures a) Postural manoeuvers - keeping operated area higher than heart Risk: Air embolism b) Artificial ventilation - lowers BP secondary to decreased venous return Pharmacological agents

Effects of posture on local blood pressure

Pharmacological agents Characteristics of an ideal agent Easy to administer Short onset time Effect should disappear quickly on discontinuation Rapid elimination No toxic metabolites Negligible effects on vital organs Predictable effect Dose dependent effect No ideal hypotensive pharmacological agent exists

Classification Alone or as adjunct Used alone As adjunct only Calcium channel blockers(nicardipine) β-blockers (propanolol,esmolol) Fenoldopam As adjunct only ACE inhibitors Clonidine Used alone Inhalational anaesthetics Sodium nitroprusside Nitroglycerine Trimetaphan Prostaglandin E1 (Alprostadil) Adenosine Remifentanil Spinal/epi anaesthesia

Principle of Induced Hypotension BP = Cardiac Output (CO) x Peripheral Vascular Resistance (PVR) CO = HR x SV PVR α 1/r4 Reduction in CO should be avoided as organ perfusion may be compromised Induce a low pressure, vasodilated circulation

Physiological effects of induced hypotension Marked physiological response designed to restore BP back to within normal range Central neuronal reflexes Arterial baroreceptors Cardiopulmonary receptors Hormonal changes Renin-angiotensin system Catecholamines

Physiological effects... Reflex rise in HR, myocardial contractility, vasomotor tone → Low pressure, hyperdynamic circulation May result in increasing vasodilator doses May require use of adjuncts

Anaesthetic Agents Drugs Site of action Predominant action Side effect Bupivacaine (spinal/ epidural) Medulla Blockade of sympathetic nervous system May need vasoconstrictor Ropivacaine (spinal/epidural) Opioids: remifentanil Heart: bradycardia none Inhalational anaesthetics (isoflurane, sevoflurane) Vessels: vasodilatation Blockade of α-adrenoceptors Resistance Need high concentration of adjuvants

Vasodilators Drugs Site of action Predominant action Side effect /Problem Sodium nitroprusside Resistance/ capacitance vsls: Vasodilatation Direct acting Cyanide toxicity Srict monitoring Nitroglycerine Capacitance vessels: vasodilatation Resistance, strict monitoring PGE1 (Alprostadil) Resistance vessels: vasodilatation Heart -↓chronotropic cost Calcium channel blockers (Nicardipine) Heart -↓ionotropic none Fenoldopam Dopamine DA1 receptor agonist Adenosine Cost Histamine release

Autonomic nervous system inhibitors Drugs Site of action Predominant action Side effect Trimetaphan Vessels: vasodilatation Heart: ↓ contractility Blockade of the ganglia of ANS Histamine release Resistance Labetalol α/β adrenoceptor antagonist Slow onset Esmolol Heart: bradycardia ↓ contractility β-adrenoceptor antagonist Cardiac failure Clonidine CNS Presynaptic α-adrenoceptor agonist Unpredictable effect ACE inhibitors

ACE inhibitors Drugs Site of action Predominant action Side effect Captopril, enalapril Vessels: vasodilatation Angiotensin ІІ inhibitors Long duration of action

Sodium nitroprusside (SNP) Nitroglycerine (NTG) Labetalol Characteristics Sodium nitroprusside (SNP) Nitroglycerine (NTG) Labetalol Onset of action Rapid onset, Rapid recovery Rapid onset, moderate slow recovery Gradual onset, Slower recovery Duration Evanescent action Short acting Long acting Method of administration IV drip (0.01% solution) IV drip (0.01% in 5%D/W or 0.9% NS) IV injection repeated in increment Mode of action Direct effect: resistance / capacitance vessels Direct : capacitance vessels predominantly α and β adrenoceptor antagonist Tachycardia Very common May occur None Cardiac output Depends on many factors (posture, HR, preload, afterload, drugs,volume status) Slight decrease Blood brain barrier Pronounced dysfunction

Sodium nitroprusside (SNP) Nitroglycerine (NTG) Labetalol Characteristics Sodium nitroprusside (SNP) Nitroglycerine (NTG) Labetalol Metabolism To cyanide, thiocyanate Degraded rapidly in liver Degraded in liver Stability Available as powder. Unstable when reconstituted. Protect from light & use within 12 hrs Stable, colourless, Absorbed by plastics Stable Dose 0.5-1.5 μg/kg/min Total dose not to exceed 1.5mg/kg in 4 hrs Plasma CN conc should not exceed 3 μmol/l Start - 10-20μg/min, 1-4 μg/kg/min 0.2-0.4mg/kg followed by increment Histamine release unknown Rebound hypertension Occurs in absence of β blockade Does not occur Intracranial pressure Increases in early stage Increases Does not increase

Cyanide Toxicity - Mechanism

Cyanide toxicity - Manifestations Resistance to high infusion rates of SNP Metabolic acidosis, raised lactate levels Elevated venous oxygen saturation Progressive hypotension unresponsive to fluids & vasopressors but responsive to thiosulphate Cardiovascular collapse No specific laboratory test but lethal cyanide level in blood is approx 500 μg/dl

Cyanide toxicity - Management Sodium thiosulphate Bolus injection - 30mg/kg Continuous infusion - 60mg/kg/hr Hydroxocobalamine (B12) Prevents ↑ in CN conc. in erythrocytes Bolus - 50mg/kg Infusion - 100mg/kg/hr Fluid replacement Acidosis correction

Monitoring during induced hypotension ECG – myocardial perfusion, drug effects Accurate BP monitoring Gold standard is direct intra-arterial measurement Capnography – disconnection alarm, indicator of air embolism Value as an index of PaCO2 is limited due to ↑dead space Pulse oximetry – allows adjustment of FiO2 to compensate for V/Q mismatch EEG/evoked potential – reserved for neurosurgery, CPB, severe hypotension Transcranial doppler velocimetry

Safe conduct of induced hypotension Onset & degree of hypotension A reliable intravenous line Horizontal position Monitoring Initiate only after intubation & steady anaes state Hypotension to be induced slowly over 10-15 min Proper posture and optimal venous drainage Adequate fluids but prevent overhydration

Safe conduct… Maintenance of near normal PaCO2 & acid base balance Hypocapnia – vasoconstriction Alter blood PH Increase oxygen consumption Inhibit hypoxic pulmonary vasoconstriction

Safe conduct… Oxygenation Increased intrapulmonary shunt Decreased cardiac output A high FiO2 (0.4-0.5 or higher) during induced hypotension is recommended

Contraindications Inexperience Infants Pregnancy Fixed cardiac output Coronary artery, renal, cerebral disease Hypovolemia Severe anaemia

Limitation Risk of tissue hypoxia by reducing microcirculatory autoregulation of vital organs and by inhibiting ANS The goal is to maintain a pressure sufficiently low to allow reduction of bleeding without suppressing microcirculatory autoregulation of vital organs

Complications Coronary artery thrombosis Cerebral thrombosis Cardiac arrest Temporary & permanent neurologic deficit Failure of technique Resistance & rebound Post-operative reactionary haemorrhage Tissue trauma

Post-operative care Maintenance of airway Provision of supplemental oxygen Analgesia Warm environment Respiratory & cardiovascular monitoring Adequacy of blood volume Positioning

Specific applications Neurosurgery - Cerebral aneurysm surgery Spinal surgery- scoliosis correction Ophthalmic surgery ENT surgery Pregnancy

Cerebral aneurysm surgery Low pressure circulation Reduces blood loss → improves visualisation Reduces aneurysm transmural pressure Safe application of clip Reduces risk of intra-operative rupture If aneurysm ruptures → less bleeding, rapid identification & control of bleeding point Vasodilators started after opening dura to avoid ↑in ICP Avoid the technique in presence of preoperative vasospasm and if a feeding artery is to be temporarily clipped

Scoliosis surgery General anaesthesia Monitoring of spinal cord function using wake-up test or somatosensory evoked potential Blood loss is massive → BP to be reduced slowly (preferably under SSEP monitoring) and only to the point at which operating conditions become satisfactory

Ophthalmic surgery ENT surgery Uveal dissection - prevention of bleeding into vitreous Choroidal melanoma - requires period of choroidal ischaemia ENT surgery High level of difficulty and impossibility of controlling bleeding by using clamps on afferent vessels, vertebral-basilar artery and external carotid artery makes induced hypotension a choice in ENT surgery

Pregnancy ↓BP → ↓ uterine blood flow → fetal asphyxia Hypotension not to be induced unless considered as life saving measure. Nitroglycerine - least toxic Close fetal heart rate monitoring mandatory – serves as a guide to safe level for hypotension and hyperventilation

Current status Surgeries with low/moderate bleeding potential e.g. middle ear, eye, neurosurgery Induced hypotension used in light of benefit/risk ratio Surgeries with moderate bleeding potential e.g. vascular, major orthopaedic surgery Benefit from combination of hemodilution with autologous transfusion with induced hypotension Surgeries with high bleeding potential e.g. cardiac surgery/liver transplantation Use of induced hypotension has decreased

Current status… The best efficacy combined with ease of use and lack of toxicity belongs to techniques of hypotensive anaesthesia that associate analgesia and hypotension at clinical concentration Epidural anaesthesia – not always practical Remifentanil along with propofol or inhalational agents at clinical concentration are preferred techniques because of their safety and ease of use

References Wylie and Churchill Davidson’s ‘A Practice of Anaesthesia’ 6th edition Wylie and Churchill Davidson’s ‘A Practice of Anaesthesia’ 7th edition Miller’s Anesthesia 5th edition International Practice of Anaesthesia by Prys-Roberts and Brown Degoute CS. Controlled hypotension. Drugs 2007; 67(7): 1053-1076