PERIOPERATIVE HYPERTENSION

Moderated by Dr. Varsha KothariPresented by Dr. Vineet Chowdhary

INTRODUCTION

• One of the most common worldwide disease• Worldwide, hypertension may affect as many as 1 billion

people and be responsible for ~7.1 million deaths per year (WHO 2002)

• Perioperative hypertension is commonly encountered in our PAC clinics in patients posted for surgery

• Many of these patients come to know of their hypertension for the first time when they come for checkup for some other reason

Definition of Hypertension

Peri-operative Hypertension

• In this article, the term perioperative refers to the time of hospitalization directly related to a surgical procedure; and includes the preoperative, intraoperative, and postoperative (ie, 3 or 4 days post) periods.

• Importance:– Increased risk of cardiovascular events– Increased post-operative morbidity and mortality– Association with end-organ damage

• Perioperative hypertension occurs in 25% of hypertensive patients that undergo surgery (Prys-Roberts et al 1971; lGoldman and Caldera 1979).

• During surgery, patients with and without preexisting hypertension are likely to develop blood pressure elevations and tachycardia during the induction of anesthesia (Erstad and Barletta 2000).

• Common predictors of perioperative hypertension are previous history of hypertension, especially a diastolic blood pressure greater than 110 mm Hg, and the type of surgery Khuri et al 1995; Aronson et al 2002,

• Perioperative Hypertension occurs duringa) Induction of anaesthesiab) Intraoperative due to pain induced

sympathetic stimulationc) Hypothermiad) Hypoxia e) Intravascular volume overloadf) 24 to 48 hours post op as fluid is mobilized

from extravascular space

Hypertensive Crisis• Patients with SBP >180 mm Hg or DBP>110 mm Hg

• Transitioning zone between hypertensive urgency and emergency that may not be readily detectable by clinical or laboratory/radiograph criteria

• In the perioperative environment, whereby patients are already hospitalized, the management of hypertensive crisis should likely be the same for both urgency and emergency

Hypertensive Crisis

Hypertensive Emergencies 1. with EOD2. Immediate treatment required

(within hours)

Hypertensive Urgency1. with No EOD2. Less rapid reduction in BP

Conditions constituting evidence of EOD

• Hypertensive encephalopathy• Intracerebral heamorrhage• Stroke• Head trauma• Ischemic heart disease (most common)– AMI– Acute LVF with P/oedema– Unstable angina

• Aortic dissection• Eclampsia• Life threatening arterial bleed

Pre Operative HypertensionHistorical Perspective

• In 1904 doctor Nicolai Sergeivich Korotkoff - clinical measurement of both systolic and diastolic components of BP.

• Over the next several decades, only a few agents were available to treat arterial HTN

• Before 1950, the operative mortality in hypertensive patients was estimated to be 32%

• With reports of profound hypotension and cardiovascular collapse associated with anesthetic induction in patients receiving drug therapy, a prevailing practice was to withhold treatment for several days preoperatively

• Prys-Roberts et al -the authors recommended that untreated high arterial pressure constitutes a serious risk to patients undergoing anesthesia and surgery, and therefore antihypertensive therapy should not be withdrawn before anesthesia without compelling reason

• Goldman and Caldera concluded those with DBP<110mm Hg behaved similar to the normotensives; mild-to-moderate HTN did not increase perioperative risk; the intraoperative management was the principal factor in lowering risks; and finally, those with HTN having other cardiovascular risks were at the highest risk of mortality

• Preoperative hypertension is frequently a hypertensive urgency, not an emergency, as it typically does not involve end organ damage and there usually adequate time to reduce the BP ( Goldberg and Larijani 1998)

• Preoperative hypertension was associated with perioperative bradycardia, tachycardia, and hypertension (Forrest et al 1992)

• Presence of preoperative hypertension increased the odds ratio for postoperative death to 3.8 times that of normotensives (Browner et al 1992).

Pre operative Concerns

• All elective surgery patients with cardio vascular risk factors should undergo pre operative optimization- control of BP, correction of electrolytes, cessation of smoking, glucose control etc.

• Hypertension mild or moderate & no associated metabolic or cardiovascular abnormalities- do not delay surgery.

• Surgery should be cancelled in patients with hypertensive end organ damage till cardio vascular status is optimized.– Anesthesia and surgery not to be cancelled only on grounds of

elevated preoperative BP, defer if end-organ damage present. (Howell et al. BJA 2004;92(4):570-583)

• Patients with chronic HTN with DBP <110 mm of Hg- don’t delay surgery

• Urgent situations- rapidly acting parenteral agents to be used

• Patients with newly diagnosed mild hypertension, treatment may be delayed till after surgery.

• Hypertensive patients must continue on their anti hypertensive drugs periopertively

• ACEI and AT 2 receptor antagonists associated with intraop hypotension- discontinue atleast 10 hours before surgery

• Symptoms of clonidine withdrawal syndrome are typically encountered 18 to 24 hours after sudden discontinuation of clonidine in patients taking more than 1.0 mg/day.

Clonidine patch pre operatively or Dexmedetomidine, an IV rapid-acting a-2 adrenergic agonist, may have utility in patients with clonidine-withdrawal syndrome

• Preoperative β blockers:– Proven to be beneficial in cardiac surgeries– For non-cardiac surgeries good results in high-risk patients but not in low-risk

patients (NEJM 1996, 2005)

• Associated with lesser incidences of perioperative ischemia• Intraoperative hypotension, precipitation of asthamatic attack, major

disadvantage

Intraoperative Concerns• Target range for intraoperative BP control:– BP days to weeks before surgery– Presence of associated comorbidity– Type of surgery

• Maintained within 20% of the preoperative level• Acute elevations in blood pressure (>20%) in the

intraoperative period are typically considered hypertensive emergencies (Goldberg and Larijani 1998)

• Stressful intraoperative events:– Intubation– Surgical incision– Emergence from GA and extubation

During induction – Normotensive: BP rises by 20- 30 mm of Hg, HR by 15 to 20 bpm - Untreated HTN- SBP rises by upto 90 mm of Hg and HR by 40 bpmPatients with pre existing HTN – more intra op labile BP leading to myocardial ischemia

• Other causes of intra-operative hypertension:– Inadequate depth of anesthesia– Pain– Hypercarbia– Hypoxemia– Bladder distension– Hypervolumia

• Exaggerated response in hypertensive patients– Increased sympathetic tone– Decreased intravascular volume

• Achieving hemodynamic stability more important than targeting an arbitrary intraoperative BP

• Reduction of DBP by 10- 15% or to approx 110 mm of Hg over a period of 30 to 60 min

• Concurrent gentle volume expansion to restore organ perfusion and to prevent sudden decline in BP after initiation of Anti hypertensive

• Chronic hypertensive – cerebral and renal autoregulation shifted to higher range – more prone to hypoperfusion if BP lowered rapidly

Postoperative concerns• APH(Acute Post operative hypertension) has been defined as a

significant elevation in BP during the immediate postoperative period that may lead to serious neurological, cardiovascular, or surgical-site complications and which requires urgent management.

• There is no standardized definition for this disorder.

• Postoperative hypertension (arbitrarily defined as systolic BP ≥190 mm Hg and/or diastolic BP 100 mm Hg on 2 consecutive readings following surgery) (Plets 1989; Chobanian et al 2003b)

• Postoperative hypertension often begins ~10–20 minutes after surgery and may last up to 4 hours (Towne and Bernhard 1980)

• Pathophysiologic mechanisms :- Activation of the sympathetic nervous and renin-angiotensin systems- Alterations in intravascular volume- Anxiety- Pain- Anesthesia emergence,

- Shivering, drug side effects, underlying HTN, and vascular disease.

• Activation of the sympathetic nervous system seems to be a fundamental component of APH, as evidenced by elevated plasma catecholamine concentrations in these patients.

• The primary hemodynamic alteration observed in APH is an increase in afterload with an increase in SBP and DBP with or without tachycardia

• Implications:– Risk of hemorrhage– Disruption of vascular or cardiac suture lines– Cerebral edema– ↑ myocardial wall stress and oxygen consumption→

myocardial ischemia

• Pain and anxiety are common contributors to BP elevations and should be treated before administration of antihypertensive therapy.

• Intravascular volume depletion increases sympathetic activity and a volume challenge should be considered.

• Other potentially reversible causes of APH include hypothermia with shivering, hypoxemia, hypercarbia, and bladder distension

Treatment• The approach to the treatment of perioperative hypertension is

considerably different than the treatment of chronic hypertension (Levy 1993).

• The initial approach to treatment is prevention. • Hypertension due to tracheal intubation, surgical incision, and

emergence from anesthesia- treated with short-acting β-blockers, ACE inhibitors, CCB or vasodilators ( Weiss and Longnecker 1993).

• Because many patients that develop postoperative hypertension do so as a result of withdrawal of their long-term antihypertensive regimen, this withdrawal should be minimized in the postoperative period

• Postoperative - rebound hypertension after withdrawal of antihypertensive medications, hypertension resulting in bleeding from vascular surgery suture lines, hypertension associated with head trauma, and hypertension caused by acute catecholamine excess (eg, pheochromocytoma). An initial approach is to reverse precipitating factors (pain, hypervolemia, hypoxia, hypercarbia, and hypothermia).

Pharmacotherapy

• Various options are available• Ideal drug- rapid acting, predictable and easily

titrated, safe, inexpensive, and convenient.• Since an immediate reduction in blood

pressure is desired, parenteral agents are discussed

Clevidipine• Third-generation dihydropyridine calcium channel blocker, which

has been approved for use in hypertensive crisis• Ultra short acting arteriolar vasodilator• Rapidly metabolized by red blood cell esterases• Reduces afterload without affecting cardiac filling pressures or

causing reflex tachycardia• Stroke volume and CO usually increase. • Clevidipine increases coronary blood flow despite a decrease in

coronary perfusion pressure indicating that the drug is a direct coronary vasodilator

• ECLIPSE (Evaluation of Clevidipine in the Perioperative Treatment of HTN Assessing Safety Events) trial showed the efficacy and safety of this agent in the treatment of APH

• Provides a safe and predictable blood pressure control and is safe when infused upto 96 hours

Enalaprilat• The RAAS becomes hyperactive during and after major

vascular surgery and is likely an important mediator of microvascular ischemic injury

• Chronic overexposure of tissue ACE alters the angiotensin II/bradykinin balance resulting in endothelial dysfunction leading to inflammation, thrombosis, apoptosis, atherosclerosis, fibrosis, and plaque rupture.

• ACE inhibitors have shown efficacy in treating hypertension associated with congestive heart failure, essential hypertension, and prevention of worsening renal function in patients with diabetic, and nondiabetic, nephropathy.

• Enalaprilat has also been used preventatively in patients undergoing craniotomy (Kross et al 2000)

• Reduces the hypertensive response to endotracheal intubation during induction of anesthesia

• Advantages - a lack of reflex tachycardia, and no effects on intracranial pressure

• Disadvantage - delayed onset of action (15 minutes). Enalaprilat does not reach peak effect for ~1 hour, and its duration of action is ~6 hours.

• Potential to cause acute renal failure, acute renal dysfunction, or hyperkalemia in patients in circulatory decompensated states or when mean arterial pressure is insufficient to support renal perfusion

• Dose- IV injection of 1.25 mg over 5 minutes every 6 hours, titrated by increments of 1.25 mg at 12- to 24-hour intervals up to a maximum of 5 mg every 6 hours.

Esmolol

• Highly selective beta blocker. Ultra short acting (onset-60 sec, duration of action- 10 – 20 min)

• Metabolism – rapid hydrolysis RBC esterase.• MOA- decreases arterial pressure by decreasing HR , Myocardial

contractility, CO

• Especially useful when CO, HR and BP is increased• Dose: 500-1000 mcg/kg loading in 1 min. Infusion between 50-300

mcg/kg

Labetalol

• Combined selective - α 1 and nonselective β adrenergic receptor blocker with an α-to β blocking ratio of 1:7

• Used in the setting of pregnancy-induced hypertensive crisis • Elimination half-life of labetalol -5.5 hours This variability makes

labetalol extremely difficult to titrate as a continuous infusion.• Labetalol reduces the systemic vascular resistance without reducing

total peripheral blood flow. In addition, the cerebral, renal, and coronary blood flows are maintained

• Labetalol maintains cardiac output (Pearce and Wallin 1994).• Some studies Meretoja et al 1980; Cruise et al 1989) noted a

significant reduction in heart rate and blood pressure along with reductions in cardiac index.

• Used with caution in patients with heart failure and avoided in patients with severe sinus bradycardia, heart block greater than first degree, and asthma.

• Loading dose – 20mg followed by incremental dosing of 20-80 mg at 10 min intervals

• Alternately - an infusion commencing at 1 to 2 mg/min and titrated up to desired control.

• Bolus injections of 1 to 2 mg/kg have been reported to produce precipitous falls in BP and should therefore be avoided

Fenoldopam• Peripheral DA- 1 receptor agonist• Peripheral vasodilatation – acts on peripheral dopamine-1 receptors• Increase in urine O/P , occasional increase in creatinine clearance-

favourable for patients with or at risk for Renal dysfunction( White and Halley 1989,Elliott et al 1990; Shusterman et al 1993)

• Onset- within 5 min, Duration of action – 30 -60 min• Initial starting dose - 0.1 μg/kg/min is recommended for fenoldopam,

titrated by increments of 0.05 to 0.1 μg/kg/min to a maximum of 1.6 μg/kg/min.

• Reflex tachycardia- used with caution in patients with myocardial ischemia

• Dose-dependent increases in intraocular pressure• Use should be avoided in patients at risk with intracranial hypertension. • Potential sulfite sensitivity may cause allergy due to sodium

metabisulfite contained in the solution

Nicardipine• Nicardipine is a short-acting dihydropyridine CCB available for both IV

and oral use.• Augments coronary blood flow & produces potent, more selective

vasodilation in the coronary circulation than in the systemic vascular bed.

• Increase both stroke volume and coronary blood flow with a favorable effect on myocardial oxygen balance

• IV nicardipine has been shown to reduce both cardiac and cerebral ischemia

• Recommended in the American Heart Association/American Stroke Association’s guidelines for the treatment of ischemic stroke when diastolic blood pressure is >120 mm Hg or the systolic blood pressure is >220 mm Hg (Adams et al 2003, 2005; Broderick et al 2007).

• Dosage is independent of the patient’s weight • Initial infusion rate of 5 mg/h, increasing by 2.5 mg/h every 5 minutes to

a maximum of 15 mg/h until the desired BP reduction is achieved

Hydralazine

• Directly acting arterial vasodilator• First-line agent for critically ill patients with pregnancy-induced

hypertension. However recent reports suggest it may have adverse feto- maternal effects (Magee LA, Cham C, Waterman EJ)

• Reflex tachycardia seen- not a good choice in patients with IHD• Avoided in patients with having dissecting aneurysm• Increased ICP due to dilatation of cerebral vessels- avoided in patients

of increased ICP• Onset of action- 5 to 15 minutes followed by a progressive and often

precipitous fall in BP that can last up to 12 hours• Its maximum effect is usually noted between 10–80 minutes• Due to the prolonged and unpredictable antihypertensive effects of

hydralazine and the inability to effectively titrate its hypotensive effect, it is best avoided in the management of hypertensive crises

Nitroglycerin• Nitroglycerin, an antianginal as well as antihypertensive drug• It is a greater venodilator than it is an arterial dilator• By decreasing preload, nitroglycerin decreases left ventricular end

diastolic volume and pressure, and reduces myocardial oxygen demand.

• NTG also dilates coronary arteries, increasing the blood supply to ischemic regions of the heart.

• Reduces BP by reducing preload and cardiac output- undesirable effects in patients with compromised cerebral and renal perfusion

• Hypotension and reflex tachycardia• Nitroglycerin is not to be considered an acceptable primary

therapy in the management of either hypertensive emergencies or urgencies ( Varon and Marik, 2003), but may be a suitable adjunct therapy

Sodium Nitroprusside• Sodium nitroprusside is an arterial and venous vasodilator that

decreases both afterload and preload• Sodium nitroprusside is often considered a drug of choice for

hypertensive emergencies : immediate onset of action and duration of effect of only 2 minutes.

• In patients with adequate circulating blood volume, nitroprusside has a predictable dose-response relationship, making it easy to titrate

• Due to its potency, rapidity of action, and the development of tachyphylaxis, the authors recommend intraarterial BP monitoring.

• In addition, sodium nitroprusside requires special handling to prevent its degradation by light

• Nitroprusside decreases cerebral blood flow while increasing intracranial pressure (ICP)

• In patients with coronary artery disease, a significant reduction in coronary perfusion pressure (coronary steal) can occur

Sodium nitroprusside

Non enzymatic

Cyanide

Liver

Thiocyanate

Eliminated through kidney

Cyanide removal hence requires proper functioning of

the kidneys , liver and bio availability of thiosulfate.

Nitroprusside therefore may cause cyanide toxicity

Occurrence of toxicity- prevalent with high infusion rates (>3 μg/kg/min) and

prolonged administration (>72

hours)

Sodium nitroprusside – also cause cytotoxicity through the release of nitric oxide, with hydroxyl radical and peroxynitrite generation leading to lipid peroxidation

• Patients receiving high infusion rates for an extended duration may require periodic thiocyanate monitoring.

• Dose- initial starting dose of 0.5 μg/kg/min• The duration of treatment should be as short as

possible• The infusion rate should not be >2 μg/kg/min. • An infusion of thiosulfate should be used in patients

receiving higher dosages (4–10 μg/kg/min) of nitroprusside

Conclusion• Acute hypertension is common and may be associated with an

increased risk of serious cardiac and neurologic, complications• The goal of controlling perioperative hypertension is to protect

organ function• The treatment of acute elevations is without a uniform approach• The treatment goal should be based on the patient’s preoperative

BP. A conservative target would be approximately 10% above that baseline

• Balance the risks associated with hypertension versus the risk of end organ hypoperfusion that may accompany antihypertensive therapy

• Newer agents such as fenoldopam, nicardipine and clevidipine are valuable additions to the arena of effective pharmacological options such as enalaprilat, labetalol, nitroglycerin, esmolol, and hydralazine

• Sodium nitroprusside should only be used when other IV antihypertensive agents are not available

References

• Perioperative hypertension management- (Joseph Varon and Paul E Marik ) - Vasc Health Risk Manag. 2008 June; 4(3): 615–627

• Perioperative Hypertensive Crisis:Newer Concepts (Manuel L. Fontes , Joseph Varon)-International Anesthesiology Clinics Volume 50, Number 2, 40–58

• Management of Perioperative Hypertensive Urgencies With Parenteral Medications (Kartikya Ahuja , Mitchell H. Charap)- Journal of Hospital Medicine

• Hypertensive Crisis- (Maria Alexandra Rodriguez, Siva K. Kumar, Matthew De Caro)- Cardiology in Review 2010;18: 102–107

Thank You