Individual guidelines and consensuses differ with regard to grading arterial pressure values above the normal range and with regard to classification into pre-hypertension and “true” arterial hypertension (AH) (1-3). The definitions, diagnostic criteria, and grading for AH described in this review are based on the guidelines of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH) (1). According to the ESC/ESH guidelines, elevated blood pressure values in all patients above the age of 16 are graded as described inTable 1. These blood pressure (BP) values refer to standard in-office measurements performed in a doctor’s office.
Anamnesis and heteroanamnesis during a prehospital intervention
Emergency medical teams are often the first medical professionals coming into contact with patients who have elevated BP values. These values are usually measured by the patient using an at-home sphygmomanometer, in most cases an automatic one. BP values measured by such a device differ only minimally from those measured in-office, although scientific consensus among hypertension experts based on current studies indicates that measurements at home show BP values approximately 5 mmHg lower than those measured in a doctor’s office (4). Thus, hypertension guidelines have lowered the value for the classification of the first grade of AH (if it is diagnosed based on values measured at home) to ≥135/85 mmHg instead of ≥140/90 (1). When arriving to an intervention, if the patient is asymptomatic (but has elevated BP), it is necessary to ascertain whether the patient is taking the antihypertensive medication prescribed to them and at which doses and frequency, as well as whether their mode of intake matches the prescription in the medical documentation. It is recommended to assess the measurement values stored on the patient’s digital pressure measurement device (if the device supports this function) and to check whether the patient is leading an BP journal in order to assess the measured values and the time since the start of the hypertensive episode. The patient’s BP value should be measured. Although there are few studies comparing the validity of measuring BP values outside the hospital in comparison with in-hospital measurements, published studies found relatively small differences in BP measured by medical personnel outside the hospital in comparison with hospital conditions: the average variation in systolic BP is between -3.8 to -4.6 mmHg, and the average variation in diastolic BP ranges from +0.42 to -3.6 mmHg (5).
When measuring BP values, correct measurement techniques should be adhered to, while making sure of the following (6):
That the patient has not consumed caffeine or nicotine for at least 30 minutes before the measurement.
The patient should be seated in an upright position for at least 5 minutes before the measurement, without crossing their legs.
The cuff length should be 80% of the circumference of the upper arm, and the width should be 40% of the upper arm.
The patient should not speak during BP measurement.
The hand should be resting on a firm surface, approximately at the level of the heart.
Tight clothing should be removed from the patient’s upper arm before commencing the measurement.
It is important to perform anamnesis/heteroanamnesis and a clinical examination in order to establish suspicion of possible secondary causes of AH and differentiate newly-developed acute AH from undiagnosed chronic AH.
The following tables provide a brief overview of the most important recommendations.Table 2 shows the most important questions related to the patient’s medical history and the potential causes, i.e., the etiology, that they are used to assess.Table 3 describes the parts of the clinical examination that are important for assessing a patient with hypertension.Table 4 lists the most common causes of secondary hypertension and related items in the anamnesis and patient status.
The role of the 12-lead electrocardiogram in emergencies
Electrocardiography (ECG) is an essential examination for AH. It is easily repeatable, non-invasive, and available in the patient’s home or the emergency services vehicle, and it is thus necessary to perform a 12-lead ECG during the first contact with the patient, repeating the examination when indicated. During the examination of a hypertensive patient, ECG has the most important role in discovering acute coronary syndrome, whether occlusion myocardial infarction (OMI) or non-occlusion myocardial infarction (NOMI). According to the 2022 recommendations of the American College of Cardiology for the treatment of acute chest pain in emergency services, physicians interpreting the ECG should pay special attention to findings that indicate OMI of one of the coronary arteries or their branches (7). Such ECG findings include ST-segment elevation in the relevant leads or equivalents such as posterior myocardial infarction with ST-elevation (STEMI), left branch block, or ventricular paced rhythm with positive or modified Sgarbossa criteria, de Winter sign, and hyperacute T-waves (7). More detailed descriptions of these findings are presented inTable 5.
In case of clinical suspicion, when the S1Q3T3 sign is present on the ECG, pulmonary embolism should be considered along with all the other diagnostic elements. Prospective studies that examined ECG findings showed that a quarter of patients with pulmonary embolism did not have the S1Q3T3 sign, i.e., no pathological ECG findings (8). Analysis of 212 ECG results showed that the S1Q3T3 sign was equally prevalent in patients with and without pulmonary embolism, and identified tachycardia (sensitivity 62.5%, specificity 77.5%) and newly-developed right branch block (sensitivity 93.3%, specificity 100.00%) as ECG findings that were statistically significantly associated with the diagnosis of pulmonary embolism (9).
Treatment approach
This review divides the treatment approaches to AH into approaches for hypertensive emergency or crisis, which is defined as elevated BP values leading to acute damage to target organs and requiring immediate reduction in order to preserve the function of affected organs and organ systems, and approaches for asymptomatic uncontrolled AH (2). The reason for this division is the fact that, although relatively rare, hypertensive emergency represents an emergency state which, if not treated in an adequate and timely manner, leads to permanent consequences in a very short period of time. Asymptomatic uncontrolled AH (previously known as “hypertensive urgency”) is the consequence of degenerative changes of the micro- and macro-vasculature that develop over several months or years that, although an independent risk factor for numerous diseases, does not represent a state of medical emergency that will lead to irreversible target organ damage within several hours (10). The choice of medication treatment and its goals differ significantly for these two pathophysiological entities and must therefore be addressed individually.
TREATMENT APPROACH FOR ASYMPTOMATIC UNCONTROLLED ARTERIAL HYPERTENSION
Approximately 6-8% of patients with elevated BP values measured at first contact with emergency services are diagnosed with AH at hospital discharge, with a prescription for antihypertensive medication (11,12). Although elevated BP values are not related to the reason for admission in approximately 75% of patients, some studies have shown that patients with significantly elevated values (grade 3 hypertension) in emergency departments had undiagnosed chronic AH, and that such findings cannot be ascribed solely to pain or anxiety (13,14).
When making a decision on commencing peroral antihypertensive treatment in a prehospital emergency setting for patients with asymptomatic uncontrolled AH, physicians must consider several important factors. Above all, they must consider the potential risk of the development of iatrogenic hypotension in patients above the age 80, fragile patients, and/or patients with comorbidities. They should also consider the benefits of short-term reduction of elevated BP values using peroral antihypertensive medication in the absence of other symptoms. Additionally, they should obtain information on the local availability of general practice physicians and the likelihood that further clinical treatment of AH will be performed. Studies that examined BP values from consecutive measurements in prehospital emergency interventions showed an average decrease of diastolic pressure of 11.6 mmHg in the second consecutive measurement that took place 20 minutes after the first. In patients with normal BP values at first measurement, the second measurement differed by only 3.5 mmHg (15). Thus, the decision to commence peroral treatment with antihypertensive medication depends on the physician’s assessment after considering factors tied to each individual patient, and the ESH guidelines recommend fixed antihypertensive therapy for AH grades 1 and 2 in order to simplify decisionmaking (1). Although they do not require emergency and immediate treatment, patients with asymptomatic and uncontrolled AH are still a vulnerable group that requires monitoring and treatment by primary healthcare physicians. A retrospective analysis conducted by Frei et al. found that 2.7% of patients presenting to emergency services due to elevated BP developed an adverse event within 7 days after being discharged from emergency services (75% of adverse events were heart failure, 25% were acute kidney damage) (16). It is crucial to emphasize the importance of consulting the patient’s family physician and recommending a treatment plan within 7 days, as well as providing instructions with regard to indications for contacting or presenting to emergency services.
If antihypertensive treatment should be commenced, the application of fixed oral antihypertensives is recommended in most patients. Combined peroral antihypertensive therapy is recommended in patients younger than 65 with newly-diagnosed AH grades 2 and 3, and the ESH/ESC Guidelines from 2018 recommend the application of a single-pill angiotensin-converting enzyme inhibitor (ACEI)/calcium antagonist ×1 perorally if the patient is edema-free, whereas a single-pill combination of an ACEI and diuretic is recommended for patients with edema. Other single-pill fixed combinations containing angiotensin receptor blockers, calcium channel blockers, or other thiazide diuretics or beta blockers (in case of tachycardia/atrial fibrillation/post-myocardial infarction) are prescribed depending on comorbid states and conditions. Starting with monotherapy is recommended in older/fragile patients (1). This usually consists of peroral application of a calcium antagonist (amlodipine 5 mg ×1) or ACEI (ramipril 5 mg). The application of anxiolytics has also been shown to be beneficial in out-of-hospital settings (17).
TREATMENT APPROACH IN HYPERTENSIVE EMERGENCY
Table 6 contains a list of the most common causes related to hypertensive emergency, which is a newly-developed acute hypertensive state that requires prompt and appropriate treatment for elevated BP. For the purpose of these recommendations, the definition of hypertensive emergency has been extended to states that present with a clinical picture of target organ damage, with BP values usually above 180/120 mmHg, given the limited capacity for laboratory and imaging examinations in prehospital emergency services.
Treatment approach for hypertensive emergencies – treatment goals
In addition to defining hypertensive emergency, it is necessary to determine treatment goals before starting medication therapy. It is recommended to monitor mean arterial pressure (MAP) values when determining the baseline and target BP values in hypertensive emergencies (18). MAP is calculated using the formula: [2x(diastolic pressure) + systolic pressure]/3. Target MAP values are between 70-100 mmHg. If BP is measured using a semiautomated cuff-oscillometric device as found on most digital blood pressure devices and monitors, the displayed value is the MAP, while systolic and diastolic pressure are approximated using formulas and algorithms specific to individual manufacturers (19). MAP has a positive correlation with the level of target organ damage, the best indicator of the severity of hypertensive emergency (20). If possible, BP should be measured in both arms over several measurements in order to obtain the most precise possible baseline MAP value.
When forming the treatment plan, the patient’s medical history must be considered, i.e., whether they are a person with chronic, preexisting AH (in which case BP reduction should be performed at a slower pace and intensity) or a previously normotensive person with suddenly-developing AH (in which case BP reduction can be performed at a higher pace and intensity).
If medical history data are not available, a reasonable goal is to reduce MAP by approximately 20% within the first 2 hours, followed by reducing MAP to 125 mmHg over the course of 2-6 hours, depending on the etiology and patient comorbidities (3,21).
Before starting antihypertensive treatment, it is recommended to treat other potential causes of elevated BP in order to optimize AH control and prevent iatrogenic hypotension. Examples of such causes are presented inTable 7.
| Cause of increased blood pressure | Therapy |
|---|---|
| Pain | Analgesic agents |
| Volume overload | Diuretic agents |
| Agitation/Acute psychosis | Antipsychotic agents |
| Obstructive uropathy/Urinary retention | Urinary catheter placement |
Choosing the best medication to treat individual patients and conditions is the decision of the treating physician, and we thus consider it inadvisable to provide specific algorithms for treatment in individual situations. Emergency patients with symptoms and signs that indicate hypertensive emergency often represent complex cases, and decisions on their treatment are multifactorial. The remainder of this text describes the pharmacokinetic and pharmacodynamic characteristics of medications that clinical practice and the literature have identified as most effective for acute reduction of elevated arterial pressure values. The availability of the medications described below varies between medical institutions.
INTRAVENOUS MEDICATIONS
1.
Intravenous medications can be divided into three groups based on the duration of their effect:
Table 8 presents the intravenous medications most commonly applied in hypertensive emergencies. Literature data lists nicardipine, clevidipine, labetalol, nitroglycerine, esmolol, and urapidil (22-27). All of these are available in the Republic of Croatia, except for nicardipine and clevidipine
2) SUBLINGUAL MEDICATIONS
Nitroglycerine can also be applied in a sublingual formulation, and it can also applied as a spray when indicated (28). One spray dose contains 400 mcg or 0.4 mg of nitroglycerine. Indications for the application of sublingual nitroglycerine in the context of hypertensive emergency are similar to those for intravenous application – acute cardiogenic pulmonary edema, acute myocardial infarction (suspected inferior wall or left ventricular myocardial infarction is a relative contraindication for their application). Absolute contraindications are the application of phosphodiesterase-5 inhibitors in a 48-hour period prior to the hypertensive episode and suspicion of elevated intracranial pressure. The most common side-effects are headache and facial erythema caused by vasodilatation. It is important to note that, given that sublingual application makes it more difficult to estimate the administrated dose, the patient should be placed in a sitting position after application of the medication due to the risk of rapid-onset hypotension. Although the sublingual formulation is not the standard for hypertensive emergency, examples from the literature show that its application is possible and effective. In a study by Prasanne et al., the authors administered one dose (0.4 mg) of sublingual nitroglycerine to patients with a hypertensive crisis and monitored the MAP values – after 10 minutes, an average MAP reduction of 16.3% was achieved (29). Hirschl et al. published studies that examined the application of sublingual nitroglycerine in doses of 0.8 mg every 10 minutes up to a cumulative dose of 3.2 mg in patients with hypertensive emergency and concluded that this form of treatment was equally effective as intravenous enalapril, but less effective than intravenous urapidil (30,31).
3) ORAL MEDICATIONS
Due to the long onset of action for most oral antihypertensive medications and the need for rapid and effective reduction of BP values in patients with hypertensive emergency, peroral antihypertensives have a limited role in prehospital emergency services. Switching to peroral therapy is generally not recommended until BP values have stabilized after intravenous application of medication. The slow onset and long duration of action in peroral application of medication should be considered, as it can lead to accumulation of the drug in the body and consequent iatrogenic hypotension, but studies have demonstrated that the peroral application of labetalol, losartan, and isosorbide dinitrate is safe and effective (32-34) (Table 9). The slow onset of action of peroral medications should also be considered in case of inclement weather or other conditions preventing the transport of patients to hospital care when treating patients on islands, in case of an insufficient venous approach (most common in oncological patients and patients with chronic kidney insufficiency), or limited capacity for osseous application of the medication (amputated limbs).
The effectiveness of different antihypertensive medications
In the section below, we present a short overview of the two most commonly used intravenous antihypertensive medications listed inTable 8 and their effectiveness and safety in various clinical conditions.
Labetalol was assessed as a antihypertensive in numerous prospective studies and was shown to be an effective, fast-acting choice: the studies report the ratios of patients with BP successfully reduced to target values was 76% after 30 minutes and 96-100% after 60 minutes (35-37). In comparisons with other antihypertensives, labetalol was shown to be more effective than intravenous nitroglycerine (36), as effective as intravenous esmolol (38), and less effective than intravenous nicardipine (35) and peroral nifedipine (37).
Urapidil is an alpha-1 adrenergic receptor antagonist used for treating hypertensive emergencies. In prehospital conditions, it has been shown to be an effective antihypertensive medication that statistically significantly reduced BP values after as little as 5 minutes, without significant unwanted adverse effects (39). In hospital conditions, urapidil was also shown to be an effective, reliable, and fast-acting medication that was superior to oral captopril in achieving target BP values (40). A metanalysis comparing urapidil with nitroglycerine for the treatment of hypertensive acute heart failure showed that urapidil had a better safety profile and equal effectiveness as nitroglycerine in the treatment of hypertensive emergency and hypertensive crisis (41). Therefore, patients with hypertensive emergency should be treated the intravenous application of the medications described above, and, if MAP cannot be calculated, the goal is to achieve a 25% reduction in BP in comparison with baseline values within a one-hour standard. The treatment goal for patients with chronic uncontrolled hypertension (the previously employed term was “hypertensive urgency”) is the gradual reduction of BP to 20% in comparison with initial values, which is achieved through the application of peroral antihypertensive therapy (42).
Discussion
In prehospital emergency medical conditions, anamnesis and clinical examination of the patient have a significant role in the assessment and diagnosis of emergency states associated with hypertension (43). Raos et al. demonstrated a significant reduction in systolic pressure in prehospital conditions if benzodiazepine was prescribed alongside antihypertensive therapy. A reduction of BP of 19.5 ± 7.1% was achieved in the group of patients with chronic uncontrolled hypertension (previously called hypertensive urgency) who were prescribed benzodiazepine in comparison with the control group (BP reduced by 10.1 ± 7.0%) taking an antihypertensive medication without benzodiazepine (44). Its beneficial added anxiolytic effect should therefore be considered in prehospital treatment. The importance of clinical follow-up and further diagnostic examinations should be emphasized in patients with chronic uncontrolled arterial hypertension (which is also the most common reason for the arrival of an emergency medicine team) throughout primary and secondary healthcare, with a recommendation for further examination and treatment and exclusion of potentially curable secondary sources of AH, with special emphasis on the importance of recommending follow-up and control in hypertensiology clinics (42,44).
In case of hypertensive emergency, diastolic pressure should not be lower than 100 to 110 mmHg, in order to prevent further target organ damage due to hypoperfusion. Excessive BP reduction can indicate cerebral, coronary, or renal ischemia and must be avoided. Exceptions comprise patients with aortic dissection, pheochromocytoma crisis, and severe preeclampsia, as well as some patients with spontaneous intracerebral bleeding that require acute pressure reduction (42).
Proper management of hypertension, whether in prehospital or hospital emergency treatment, is crucial for the prevention of target organ damage as well as the prevention of cerebral, cardiac, renal, and vascular remodeling and untimely fibrosis of target organs such as the brain, heart, kidneys, and the vascular system.
Conclusion
Emergency service providers, as a form of a “safety net” for the healthcare systems, have an important role in informing patients on the importance of subsequent clinical treatment for chronic uncontrolled hypertension.
Knowledge of the etiology of emergency states related to hypertension and hypertensive emergency, as well as the pharmacokinetic and pharmacodynamic characteristics of medications available to physicians in emergency medical services, is crucial in order to provide patients with the best possible care in the context of available options, with the goal of achieving coordinated treatment and communication across prehospital and in-hospital emergency services.