1. Perioperative hypertension is commonly encountered and can increase morbidity and mortality. It occurs during induction of anesthesia, intraoperatively due to pain or other factors, and in the first few postoperative days. 2. Treatment involves first identifying and addressing reversible causes while also preventing sharp drops in blood pressure. Several intravenous antihypertensive medications can be used including clevidipine, enalaprilat, esmolol, labetalol, fenoldopam, and nicardipine. The goal is to lower blood pressure by 10-15% or to 110 mmHg over 30-60 minutes to reduce risk. 3. Special considerations for preoperative, intraoperative, and postoperative hypertension

1. PERIOPERATIVE HYPERTENSION
Moderated by Dr. Varsha Kothari
Presented by Dr. Vineet Chowdhary

2. 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

3. Definition of Hypertension

4. 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

5. • 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,

6. • Perioperative Hypertension occurs during
a) Induction of anaesthesia
b) Intraoperative due to pain induced
sympathetic stimulation
c) Hypothermia
d) Hypoxia
e) Intravascular volume overload
f) 24 to 48 hours post op as fluid is mobilized
from extravascular space

7. 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 EOD
2. Immediate treatment required
(within hours)
Hypertensive Urgency
1. with No EOD
2. Less rapid reduction in BP

8. 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

9. Pre Operative Hypertension
Historical 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

10. • 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).

12. 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)

13. • 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.

14. • 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

15. 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)

16. • 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 bpm
Patients with pre existing HTN – more intra op labile BP leading
to myocardial ischemia

17. • 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

18. • 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

19. 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)

20. • 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

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

22. • 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

23. 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).

24. 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

25. 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

26. 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)

27. • 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.

28. 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

29. 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.

30. • 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

31. 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

32. 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

33. 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

34. 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

35. 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

36. 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

37. • 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

38. 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

39. 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