Actu Anaesthesiol Scand 1993: 37, Supplementum 99: 5-9

Incidence and aetiology of perioperative hyper tension J. B. LESLIE Department of Cardiac Anaesthesia, Duke University Medical Center, Durham, North Carolina, USA

The reported incidence of perioperative hypertension associated with coronary artery bypass-graft (CABG) surgery ranges from 3 ( H K P / o , which may reflect the various definitions of the condition as well as differences in the patients’ preoperative states. Systolic, diastolic and mean arterial blood pressures are variously used to define perioperative hypertension, but absolute values range from a target systolic blood pressure of below 170 mmHg in some studies to below 110 mmHg in others. Patients’ preoperative states have been extensively studied to determine potential risk factors. The majority of these studies indicate that perioperative hyperten- sion is predictive of perioperative cardiac morbidity, but others do not confirm this finding, rendering the issue unresolved. The consequences of perioperative hypertensive episodes include bleeding from vascular suture lines, cerebrovascular haemorrhage or subendocardial ischaemia, and are associated with a mortality rate that may approach 50%. Increases in peripheral vascular resistance (PVR), caused by elevated levels of circulating catecholamines, appear to be the primary aetiology. Antihypertensive agents which correct or prevent the increase in PVR would appear to be the most appropriate therapy. However, no single agent appears to be ideal for all hypertensive episodes, suggesting multiple potential aetiologies.

Key words: Aetiology; coronary artery bypass-grafting; incidence; perioperative hypertension.

DEFINITIONS Postoperative hypertension following coronary artery bypass-grafting (CABG) surgery was first defined in 1973 as a sustained arterial pressure elevation with no obvious cause (1). This excluded transient elevations associated with pain, irritability, shivering, “fighting” the ventilator, intolerance to endotracheal intubation or the administration of vasopressor agents. Levels de- fining hypertensive episodes were arbitrarily set at a diastolic blood pressure increase to 100 mmHg or more in preoperatively normotensive patients, or an increase of at least 30 mmHg in preoperatively hypertensive patients. The definition remains fairly non-specific, but relates to an elevation in blood pressure during the first 3 hours after CABG surgery that is likely to increase perioperative morbidity. Recent clinical studies have variously selected systolic, diastolic or mean arterial pressure as the starting points for initiating therapy to treat perioperative hypertension. The majority of studies take systolic blood pressure as their indicator, but the absolute level varies from 110 mmHg up to 175 mmHg (2, 3). Diastolic blood pressures above 95 mmHg (4) or 110 mmHg (3, 5) and mean arterial pressures of 90 mmHg (6), 100 mmHg (7) or 107 mmHg (3) have also been selected as threshold values for treatment. The elevation in blood pressure should be sustained over a period of time, usually more than 10 min, to avoid fluctuations due to the specific under-

lying transient causes listed above. Durkin and col- leagues (8) introduced a more refined system of nu- merical values to determine when to treat and to define therapeutic success or failure. O n the basis of preopera- tive blood pressure levels, treatment was started when- ever systolic blood pressure exceeded a “trigger” value. Treatment success was defined as a return of systolic blood pressure control, and failure was defined as a continued elevation of systolic blood pressure to a pre- determined series of failure values at which other thera- peutic measures should be considered. Other thera- peutic trials have taken percentage decreases of be- tween 15% and 30% or specific numerical values (for example, a mean arterial pressure of 85 rf: 5 mmHg) as measures of success, the patient being regarded as non-hypertensive when these values are achieved.

INCIDENCE Perioperative hypertension occurs in less than 4% of patients undergoing major non-cardiac surgery and increases to just over 5% in valve replacement surgery because of rheumatic heart disease ( 1). The incidence increases dramatically with coronary artery bypass- grafting, ranging from 30-80% (1, 3, 9-12), with higher frequencies in patients who have severe burns, head injury or intracranial pathology, phaeochromo- cytoma, eclampsia, pre-eclampsia, hyperthyroidism, renal disease, amphetamine or cocaine overdose, or

6 J. B. LESLIE

myocardial ischaemia due to atherosclerosis or coro- nary spasm. Perioperative hypertension may lead to rupture of vascular sutures (1 3), cerebrovascular haemorrhage, or subendocardial ischaemia ( 14).

The incidence of perioperative hypertension may be increasing as higher-risk procedures are undertaken in patients who are already at higher risk. In addition, the population is ageing. In the United States, for example, the proportion of the population over 65 years of age is expected to reach 16% by the year 2000 and 25% by 2025 (15). Moreover, the number of inpatient operations in this age group has increased at nearly four times the rate in the general population (16)-

AETIOLOGY Haemodynamic alterations Blood pressure is not an isolated variable; the major determinants of blood pressure are cardiac output (CO) and total peripheral resistance (TPR) - thus, blood pressure = CO x TPR. The TPR is calculated after determining mean arterial blood pressure (MAP), central venous pressure (CVP) and CO. Car- diac output is the product of stroke volume (SV) and heart rate - thus, CO = SV x heart rate. Heart rate is dependent on numerous factors, including the intrinsic automaticity, adrenergic tone and ventricular filling. The SV is dependent on the venous return, adrenergic tone, valvular competence and ventricular compli- ance. Thus, increases in SV, heart rate, CO, and TPR, or changes in the numerous other factors that modify these variables, may lead to hypertension (Table 1).

Numerous studies have identified the principal me- diators of postoperative hypertensive episodes and con- firmed the relationships (9). In general, elevated levels of catecholamines, both adrenaline (epinephrine) and noradrenaline (norepinephrine), have been docu- mented (3, 13). This is not surprising considering that catecholamines and adrenergic “tone” affect all four of the haemodynamic variables that contribute to the development of perioperative hypertension. Catechol- amine release may occur in response to the underlying disease process or as part of the normal homeostatic

reparative process. The major hypertensive episodes are generally associated with the neuroendocrine re- sponses elicited as a consequence of the pain and stress of the surgical procedure (1 7). Thus, an increased TPR due to hypothermia and vasoconstriction (alpha agonist) combine with an increased SV (decreased peripheral capacitance) and increased contractility (beta agonist = increased heart rate and CO) to pro- duce hypertension.

As already noted, the management of heart rate, blood pressure and myocardial ischaemia is multifac- torial. Myocardial ischaemia and infarction may be the result of an imbalance in the supply/demand ratio of oxygen-metabolite delivery and utilization by the myocardium. The increased demand for oxygen by the myocardium is closely controlled by increasing its delivery through an increased coronary blood flow. There is a close relationship between myocardial oxy- gen requirements and the level of contractility, heart rate and wall tension.

Patients with atherosclerosis or coronary spasm have a limited amount of compensatory increase of coronary flow delivery. Such patients, who have coronary artery disease, are also the patients who frequently experience hypertensive and tachycardiac episodes in the peri- operative period and in the intensive care unit (ICU). In three large multicentre studies (18-20), the admin- istration of beta-blockers to patients with ischaemic heart disease and myocardial infarction was found to decrease postinfarction mortality. Consequently, vari- ous beta-blockers have also proved to have potential therapeutic efficacy in the management of perioperat- ive hypertension and tachycardia in high-risk patients in the ICU (21, 22).

In many situations, the balance between myocardial oxygen supply and demand may be more critical than the absolute blood pressure, ventricular filling press- ure, heart rate or CO. An inadequate oxygen supply or excessive oxygen demand may exceed the capacity of the coronary arteries to provide the required blood flow. Ischaemia and potential infarction may result from either hypotension (23-25), or the “stress” of tachycardia, increased contractility, and increased wall tension during hypertensive episodes. Perioperat-

Table 1 Haemodvnamic variables contributing to hvmrtension. - ,. Cardiac output Total peripheral resistance Heart rate Stroke volume

Heart rate Mean arterial pressure Automaticity Venous return Stroke volume Central venous pressure Conduction Ventricular compliance

Adrenergic tone Adrenergic tone Adrenergic tone Adrenergic tone Cardiac output Ventricular filling and stretch Valvular competence

Circulating vasoactive compounds and mediators

AETIOLOGY OF PERIOPERATIVE HYPERTENSION 7

ive hypertension or hypotension in the ICU is a patho- physiological state that warrants rapid assessment and appropriate treatment.

Predictors of hypertension The first major study of perioperative hypertension (1) reported that preoperative hypertension did not influence outcome. Indeed, the incidence of peri- operative hypertension was slightly more frequent in the preoperatively normotensive patients than the hy- pertensives. The authors considered that this may be due to the lingering effects of preoperative antihyper- tensive therapy. No correlation between preoperative hypertension and postoperative hypertension could be found in another study of CABG patients, 54% of whom developed perioperative hypertension (3) . More recent studies (6, 26) suggest that hypertension is more likely to occur postoperatively in patients with known, documented hypertension. In one study (6), nearly two-thirds of the patients with perioperative hyperten- sion had previously documented hypertension.

Other potential predisposing factors include hypo- thermia, elevated plasma renin and angiotensin levels (3, 9, 27), elevated plasma adrenaline and noradren- aline levels (3, 12, 28), or pressor reflexes originating from the heart, great vessels or coronary arteries (12, 29, 30).

If the patient presents with severe or moderate hy- pertension, or a history of antihypertensive therapy, the clinician is then able to initiate appropriate therapy early in the patient’s hospitalization period. This may help to prevent the development of severe hypertensive episodes and, therefore, potentially reduce the peri- operative morbidity and mortality.

The severity of the hypertensive episodes may often be predicted by the associated circumstances of the patient’s disease (Table 2). It is important to note, however, that the patient may initially present with a normal blood pressure or even hypotension. In these cases, the process of resuscitation and restoration of SV may lead to the development of severe hypertension.

Table 2 Conditions commonly associated with severe perioperative hyperten- sion.

Malignant hypertension Severe burns Severe head injury Phaeochromocytoma Encephalopath y Eclampsialpre-eclampsia Abrupt drug withdrawal Monoamine-oxidase inhibitorslfoods Amphetaminelcocaine overdose Hyperthyroidism

Table 3 Pathophysiological conditions commonly associated with moderate- to-severe episodes of perioperative hypertension.

Myocardial ischaemia/infarction Aortic dissection Intracranial haemorrhagelinfarction Post-coronary artery bypass-grafting Post-peripheral or aortic vascular surgery Post-intracranial surgery Post-renal transplantation Untreated hypertensive patient Treated hypertensive patient Post-trauma resuscitation Hypothermia Congestive heart failure “Stress response”

Table 4 Non-cardiac conditions commonly associated with perioperative hy- pertension.

Pain Hypoxaemia Hypercarbia Hypothermia Intravascular volume overload Malignant hyperthermia

Furthermore, there are other pathophysiological conditions that are often associated with moderate hy- pertension which may progress to severe episodes of hyper- or hypotension. The hallmark is the potential for haemodynamic instability with wide variations in blood pressure and myocardial performance in the same patient at various periods during their hospital- ization. These moderate-to-severe episodes of hyper- tension are listed in Table 3. The management of such patients and their wide-ranging haemodynamic variabilities in the perioperative period can be clini- cally challenging.

The clinician should also be aware of other, perhaps even more common, causes of perioperative hyperten- sion. Moderate-to-severe hypertension may be a physiological expression of other major abnormalities that may not be related to underlying cardiovascular abnormalities (Table 4). In all episodes of perioperat- ive hypertension, these non-cardiac aetiologies should first be sought as either the primary cause of the hyper- tension or as coincident with other causes of the haemodynamic abnormalities. When found, they should be aggressively treated in the hospitalized pa- tient.

Consequences of perioperative hypertension Perioperative cardiac morbidity has been comprehen- sively reviewed (31) in relation to non-cardiac and

8 J. B. LESLIE

cardiac procedures. Surgery involving the thoracic and upper abdominal organs is accompanied by a two- to three-fold higher risk of complications, and procedures lasting longer than 3 hours also increase perioperative cardiac morbidity. Patients with coronary artery dis- ease undergoing major vascular surgery are at a signifi- cantly increased risk of perioperative myocardial in- farction, congestive heart failure and cardiac death. Infarction rates as high as 15-40% have been reported during such procedures (32, 33). The intraoperative stresses associated with vascular surgery, combined with the underlying coronary artery disease, appear to be responsible for the high complication rate (32). In studies assessing specifically the relationship between hypertension and outcome, a correlation has been re- ported (34, 35). In the latter study, the perioperative reinfarction rate was significantly higher in the hyper- tensive patients (9.2% us 4.4% in non-hypertensive patients). However, the relationship is not clearcut, as a number of studies have failed to show any correlation between hypertension and outcome (36, 37), although these were in non-cardiac surgery patients. There is certainly evidence to show that perioperative hyper- tension can cause cardiac ischaemia (38) and de- pressed ventricular performance (39).

CONCLUSIONS Perioperative hypertension is a pathophysiological state that warrants rapid assessment and appropriate treatment. Several studies indicate that the develop- ment of a myocardial infarction or major stroke in association with anaesthesia and/or surgery predicts a mortality rate which may be as high as 50%. The question of whether emergent control of hypertension will reduce morbidity has, as yet, not been answered by any of the well-controlled studies carried out so far, but most clinicians believe this to be a desirable goal. The incidence of hypertension is greater in the elderly patient; therefore, as the number of surgical procedures and ICU admissions for the elderly increase, so will the problem of perioperative hypertension.

As more and more antihypertensive agents become clinically available, it becomes increasingly important for the clinician to understand the pharmacological and pharmacodynamic differences between the various antihypertensive treatments, and to have guidelines for determining which drug to prescribe for the diver- sity of clinical presentations of perioperative hyperten- sion. The ideal parenteral antihypertensive for use in the perioperative period should provide a rapid onset, a titratable level of control and duration, and high efficacy and safety, and be relatively easy to administer. Realistically, however, because of the multiple poten-

tial aetiologies of these hypertensive episodes, no single antihypertensive is likely to be ideal for all perioperat- ive hypertensive episodes.

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Address: John B. Leslie MD Department of Cardiac Anesthesia Duke University Medical Center 3432 Duke University Hospital North P.O. Box 3094 Durham, North Carolina 27710 USA