Authors

• Điđi Delalić — Sveučilište u Zagrebu, Medicinski fakultet, Zagreb, Hrvatska — ORCID: 0000-0003-2102-2586
• Anđela Simić — Zavod za hitnu medicinu Varaždinske županije, Varaždin, Hrvatska — ORCID: 0000-0003-0428-1658
• Višnja Nesek Adam — Klinička bolnica Sveti Duh, Zagreb, Hrvatska — ORCID: 0000-0002-6521-4136
• Ingrid Prkačin — Sveučilište u Zagrebu, Medicinski fakultet, Zagreb, Hrvatska — ORCID: 0000-0002-5830-7131

Abstract

Arterial hypertension is the most common cause of cardiovascular diseases and mortality. It significantly contributes to the incidence of other chronic diseases, the most frequent being myocardial infarction and stroke. Arterial hypertension, whether chronically uncontrolled or especially in case of hypertensive emergency, represents a complex state that must be adequately assessed and managed. Hypertensive emergencies are not common in the general population, but represent a serious health emergency that can rapidly lead to irreversible damage and loss of function of target organs if not treated adequately. Prompt and effective treatment in prehospital emergency care significantly contributes to the overall quality of the healthcare system.

Keywords

arterijska hipertenzija, izvanbolnička hitna medicinska služba, arterial hypertension, prehospital emergency services

DOI

Full Text

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 in **Table 1**. These blood pressure (BP) values refer to standard in-office measurements performed in a doctor’s office. ### TABLE 1: Grading of hypertension according to blood pressure values and the current Guidelines for the Management of Arterial Hypertension ( 1 ). | **Grade of hypertension** | **Systolic blood pressure (mmHg)** | | **Diastolic blood pressure (mmHg)** | | --- | --- | --- | --- | | Optimal blood pressure | 20 mmHg difference in systolic BP between the upper and lower extremities | Coarctation of the aorta | Transthoracic echocardiography Multislice computed tomography of the aorta | | Renal artery murmur (auscultated paraumbilically) Increased serum creatinine concentration and/or proteinuria on urine dipstick test | Renal artery stenosis | Renal artery Doppler ultrasonography Multislice computed tomography of the renal arteries | | Bradycardia/Tachycardia Dysmenorrhea/Amenorrhea Sudden weight loss or weight gain | Functional disorders of the thyroid gland | Laboratory workup: measurement of serum thyroid stimulating hormone, free serum triiodothyronine, free serum thyroxine, anti-thyroid peroxidase antibodies | | Hypokalemia Hypernatremia | Primary hyperaldosteronism | Laboratory workup: measurement of serum renin, aldosterone, aldosterone/renin ratio Multislice computed tomography of the adrenal glands | | Snoring during sleep Apneic episodes and sudden waking from sleep Fatigue during daytime | Obstructive sleep apnea syndrome | Polysomnography, drug induced sleep endoscopy | | Pallor/Headache/Syncope Tachycardia Paroxysmal BP surges | Pheochromocytoma | Laboratory workup: measurement of metanephrine/normetanephrine and adrenaline/noradrenaline in a 24h urine sample | | Abdominal obesity “Buffalo hump” “Moon facies” Hyperglycemia Red abdominal striations | Cushing’s disease/Insulin resistance | Laboratory workup: measurement of cortisol in a 24h urine sample Dexamethasone suppression test Measurement of serum insulin concentration and insulin resistance index | ## 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 in **Table 5**. ### TABLE 5: Electrocardiography findings correlated with myocardial ischemia (adapted from the 2022 American College of Cardiology guidelines on the evaluation of chest pain in the emergency department ( 7 )). | **Finding** | **Criteria** | | --- | --- | | **ST-Elevation Myocardial Infarction equivalents** | | | Posterior STEMI | Horizontal ST-segment depression in V1-V3 Dominant R-wave (R/S ratio >1) in V2 Upright T waves in anterior leads Prominent and broad R-wave (>30 ms) Confirmation by ST-segment elevation of ≤0.5 mm in at least 1 of leads V7-V9 | | de Winter Sign | Tall, prominent, symmetrical T waves arising from upsloping ST-segment depression >1 mm at the J-point in the precordial leads 0.5-1 mm ST-segment elevation may be seen in lead aVR | | Hyperacute T-waves | Broad, asymmetric, peaked T waves may be seen early in ST-elevation myocardial infarction Serial electrocardiograms over very short intervals are useful to assess for progression to ST-Elevation Myocardial Infarction | | Left bundle branch block or ventricular paced rhythm with Smith-modified Sgarbossa Criteria | Positive if any of the following are present: Concordant ST-segment elevation of 1 mm in leads with a positive QRS complex Concordant ST-segment depression of 1 mm in V1-V3 ST-segment elevation at the J-point, relative to the QRS onset, is at least 1 mm and has an amplitude of at least 25% of the preceding S-wave | | Left bundle branch block or ventricular paced rhythm with Sgarbossa Criteria | A total score ≥3 points is required: Concordant ST-segment elevation ≥1 mm in leads with a positive QRS complex (5 points) Concordant ST-segment depression ≥1 mm in leads V1-V3 (3 points) Discordant ST-segment elevation ≥5 mm in leads with a negative QRS complex (2 points) If there is discordant ST-segment elevation ≥5 mm, consider ST/S ratio <-0.25 | | **Findings consistent with acute or subacute myocardial ischemia** | | | Wellens syndrome | Biphasic or deeply inverted and symmetric T waves in leads V2 and V3 (may extend to V6) Recent angina Absence of Q waves | | ST-segment depression | Horizontal or downsloping ST-segment depression ≥0.5 mm at the J-point in 2 or more contiguous leads is suggestive of myocardial ischemia | | Inverted T-waves | May be seen in ischemia (subacute) or infarction (may be fixed and associated with Q waves) in continuous leads | | ST-segment elevation in lead aVR | ST-segment elevation in aVR ≤1 mm Multi-lead ST-segment depression in leads I, II, Val, and/or V4-V6 Absence of contiguous ST-segment elevation in other leads | 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. ### TABLE 6: The most common etiologies leading to hypertensive emergencies. | Myocardial infarction | | --- | | Pulmonary edema | | Preeclampsia | | Cerebrovascular incident | | Hyperthyroidism | | Aortic dissection | | Sympathomimetic intoxication (i.e., cocaine) | | Malignant hypertension with acute kidney injury | ## 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 in **Table 7**. ### TABLE 7: The most common reversible secondary causes of an increase in blood pressure. | **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 Intravenous medications can be divided into three groups based on the duration of their effect: [list-style:lower-alpha] 1. Short-acting medications Duration of action lower than 30 minutes – applied in continuous infusion Short-acting effect allows titration 2. Intermediate-acting medication Duration of action between 30 minutes to 2 hours – applied in continuous infusion Titration possible, but not as effective as in short-acting medications 3. Long-acting medications Duration of action longer than 2 hours – bolus application Titration is more difficult due to long duration of action **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 ### TABLE 8: Intravenous medications for blood pressure regulation in hypertensive emergency. | **Name** | **Onset of action/Duration of action** | **Contraindications** | **Dose** | **Comments** | | --- | --- | --- | --- | --- | | Labetalol | Onset of action: 5-10 min Duration of action: 3-6 h | Bradycardia, Atrioventricular block, Sick sinus syndrome, Cardiogenic pulmonary edema, Asthma exacerbation, Acute sympathomimetic intoxication | Applied in boluses. First bolus 20 mg, followed by a 40 mg bolus, then an 80 mg bolus up to 3 times maximum. Obligatory spacing between boluses: 15 minutes. Scheme: 20 mg - 40 mg - 80 mg-80 mg - 80mg Maximum allowed cumulative dose: 300mg Once the desired BP is achieved, apply 10-20 mg boluses according to MAP, not more often than every 10 minutes. | May cause bradycardia, hyperkalemia | | Nitroglycerin | Onset of action 2 min Duration of action: 5-10 min | Use of phosphodiesterase 5 inhibitors within 48 hours (sildenafil, vardenafil, tadalafil). Suspected increased intracranial pressure. | Applied as an infusion: 50-300 mcg/min, titrate according to MAP | Medication of choice in acute cardiogenic pulmonary edema. Coronary venodilator, indicated in acute myocardial infarction (inferior/right sided myocardial infarction are relative contraindications) | | Esmolol | Onset of action: 1-2 min Duration of action: 10-30 min | Bradycardia, Atrioventricular block, Sick sinus syndrome, Cardiogenic pulmonary edema, Asthma exacerbation, Acute sympathomimetic intoxication | Loading bolus 0.5 mg/kg, then a 50 mcg/kg/min infusion. If BP remains uncontrolled: repeat bolus 0.5 mg/kg, followed by a 50 mcg/kg/min infusion. Titrate infusion to MAP (max infusion rate 200 mcg/kg/min) | May cause bradycardia, hyperkalemia | | Urapidil | Onset of action 5 min Duration of action: 3 h | Aortic outflow tract stenosis. Arterio-venous shunt. | Starting dose: 25mg bolus. If BP remains uncontrolled: repeat 25 mg bolus after 10 minutes. In case of persistently elevated BP: 50 mg bolus 10 minutes after the second bolus, followed by an infusion: 5-40 mg/h | Most common medication for the management of hypertensive emergency in Croatia | ## 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). ### TABLE 9: Peroral medications for blood pressure regulation when transport if the patient to hospital care is not possible. | **Name** | **Onset of action/** **Duration of action** | **Contraindications** | **Dose** | **Comments** | | --- | --- | --- | --- | --- | | Labetalol | Onset of action: 2 h Duration of action: 10 h | Bradycardia, Atrioventricular block, Sick sinus syndrome, Cardiogenic pulmonary edema, Asthma exacerbation, Acute sympathomimetic intoxication | 1 200 mg oral tablet every 12 h. In case of suboptimal effect, another 200 mg oral tablet can be applied 2-4 h following the first. Maximum allowed dose: 1000 mg orally every 12 h | May cause bradycardia, hyperkalemia. In stable patients, following successful BP control with intravenous labetalol and stable BP values, treatment can be continued with peroral labetalol | | Losartan | Onset of action: 4-6 h Duration of action: 24 h | Hyperkalemia, Acute kidney injury, Previously reported cough or angioedema with angiotensin converting enzyme inhibitors or angiotensin receptor blockers | One 50 mg oral tablet once daily. Maximum allowed dose: 100 mg daily | Efficacy differs between patients, depending on the renin/angiotensin/aldosterone system activity level of individual patients | | Isosorbide dinitrate | Onset of action: 1-2 h Duration of action: 8 h | Increased intracranial pressure. Obstructive hypertrophic cardiomyopathy | One 20 mg oral tablet every 8 h. Maximum allowed dose: One 40 mg oral tablet every 8 hours | May cause reflex tachycardia | ## 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 in **Table 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.

Literature

1. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018 October;36(10):1953–2041. https://doi.org/10.1097/HJH.0000000000001940
2. nger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. 2020 International Society of Hypertension global hypertension practice guidelines. J Hypertens. 2020 Jun;38(6):982-1004. https://doi.org/10.1097/HJH.0000000000002453
3. Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2018 May 15;71(19):e127–248. https://doi.org/10.1016/j.jacc.2017.11.006
4. Bliziotis IA, Destounis A, Stergiou GS. Home versus ambulatory and office blood pressure in predicting target organ damage in hypertension: a systematic review and meta-analysis. J Hypertens. 2012 July;30(7):1289–99. https://doi.org/10.1097/HJH.0b013e3283531eaf
5. Cienki JJ, DeLuca LA. Agreement between emergency medical services and expert blood pressure measurements. J Emerg Med. 2012 July;43(1):64–8. https://doi.org/10.1016/j.jemermed.2011.02.018
6. Beevers G, Lip GY, O’Brien E. ABC of hypertension: Blood pressure measurement. Part II-conventional sphygmomanometry: technique of auscultatory blood pressure measurement. BMJ. 2001 April 28;322(7293):1043–7. https://doi.org/10.1136/bmj.322.7293.1043
7. Kontos MC, de Lemos JA, Deitelzweig SB, Diercks DB, Gore MO, Hess EP, et al. 2022 ACC Expert Consensus Decision Pathway on the Evaluation and Disposition of Acute Chest Pain in the Emergency Department: A Report of the American College of Cardiology Solution Set Oversight Committee. J Am Coll Cardiol. 2022 November 15;80(20):1925–60. https://doi.org/10.1016/j.jacc.2022.08.750
8. Chan TC, Vilke GM, Pollack M, Brady WJ. Electrocardiographic manifestations: pulmonary embolism. J Emerg Med. 2001 October;21(3):263–70. https://doi.org/10.1016/S0736-4679(01)00389-4
9. Rodger M, Makropoulos D, Turek M, Quevillon J, Raymond F, Rasuli P, et al. Diagnostic value of the electrocardiogram in suspected pulmonary embolism. Am J Cardiol. 2000 Oct 1;86(7):807-9, A10. https://doi.org/10.1016/S0002-9149(00)01090-0
10. Jacobs ZG. Hypertensive “Urgency” Is a Harmful Misnomer. J Gen Intern Med. 2021 September;36(9):2812–3. https://doi.org/10.1007/s11606-020-06495-6
11. Tilman K, DeLashaw M, Lowe S, Springer S, Hundley S, Counselman FL. Recognizing asymptomatic elevated blood pressure in ED patients: how good (bad) are we? Am J Emerg Med. 2007 March;25(3):313–7. https://doi.org/10.1016/j.ajem.2006.09.007
12. Bohan J, Fullerton L, Oakland B, Oldewage J. Hypertension in the ED: a multifaceted intervention to change provider practice. Am J Emerg Med. 2011 September;29(7):796–801. https://doi.org/10.1016/j.ajem.2010.05.003
13. Baumann BM, Abate NL, Cowan RM, Chansky ME, Rosa K, Boudreaux ED. Characteristics and referral of emergency department patients with elevated blood pressure. Acad Emerg Med. 2007 September;14(9):779–84. https://doi.org/10.1197/j.aem.2007.05.008
14. Tanabe P, Persell SD, Adams JG, McCormick JC, Martinovich Z, Baker DW. Increased blood pressure in the emergency department: pain, anxiety, or undiagnosed hypertension? Ann Emerg Med. 2008 March;51(3):221–9. https://doi.org/10.1016/j.annemergmed.2007.10.017
15. Pitts SR, Adams RP. Emergency department hypertension and regression to the mean. Ann Emerg Med. 1998 February;31(2):214–8. https://doi.org/10.1016/S0196-0644(98)70309-9
16. Frei SP, Burmeister DB, Coil JF. Frequency of serious outcomes in patients with hypertension as a chief complaint in the emergency department. J Am Osteopath Assoc. 2013 September;113(9):664–8. https://doi.org/10.7556/jaoa.2013.032
17. Watson K, Broscious R, Devabhakthuni S, Noel ZR. Focused Update on Pharmacologic Management of Hypertensive Emergencies. Curr Hypertens Rep. 2018 June 8;20(7):56. https://doi.org/10.1007/s11906-018-0854-2
18. Babbs CF. Oscillometric measurement of systolic and diastolic blood pressures validated in a physiologic mathematical model. Biomed Eng Online. 2012 August 22;11:56. https://doi.org/10.1186/1475-925X-11-56
19. Liu J, Hahn JO, Mukkamala R. Error mechanisms of the oscillometric fixed-ratio blood pressure measurement method. Ann Biomed Eng. 2013 March;41(3):587–97. https://doi.org/10.1007/s10439-012-0700-7
20. Papaioannou TG, Protogerou AD, Vrachatis D, Konstantonis G, Aissopou E, Argyris A, et al. Mean arterial pressure values calculated using seven different methods and their associations with target organ deterioration in a single-center study of 1878 individuals. Hypertens Res. 2016 September;39(9):640–7. https://doi.org/10.1038/hr.2016.41
21. van den Born BH, Lip GYH, Brguljan-Hitij J, Cremer A, Segura J, Morales E, et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur Heart J Cardiovasc Pharmacother. 2019 January 1;5(1):37–46. https://doi.org/10.1093/ehjcvp/pvy032
22. (February 2, 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/019734s030lbl.pdf
23. (February 2, 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2011/022156s003lbl.pdf
24. Aronson S, Dyke CM, Stierer KA, Levy JH, Cheung AT, Lumb PD, et al. The ECLIPSE trials: comparative studies of clevidipine to nitroglycerin, sodium nitroprusside, and nicardipine for acute hypertension treatment in cardiac surgery patients. Anesth Analg. 2008 October;107(4):1110–21. https://doi.org/10.1213/ane.0b013e31818240db
25. (February 2, 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213330s000lbl.pdf
26. (February 2, 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019970s015lbl.pdf
27. (February 2, 2023). https://halmed.hr/upl/lijekovi/PIL/Esmocard-PIL.pdf
28. (February 2, 2023). https://halmed.hr/upl/lijekovi/PIL/PIL_UP-I-530-09-15-02-442.pdf
29. Prasanna N, Dissanayake HA, Constantine GR. Sublingual nitroglycerin for early blood pressure control in hypertensive emergencies: observations from an emergency department clinical audit in Sri Lanka. BMC Res Notes. 2018 June 5;11(1):355. https://doi.org/10.1186/s13104-018-3460-0
30. Hirschl MM, Schreiber W, Woisetschläger C, Kaff A, Raab H. Sublinguales Nitroglyzerin oder intravenöses Enalaprilat in der präklinischen Behandlung von hypertensiven Patienten mit Lungenödem [Sublingual nitroglycerin or intravenous enalaprilat in preclinical treatment of hypertensive patients with pulmonary edema]. Z Kardiol. 1999 Mar;88(3):208-14. German. https://doi.org/10.1007/s003920050277
31. Schreiber W, Woisetschläger C, Binder M, Kaff A, Raab H, Hirschl MM. The nitura study--effect of nitroglycerin or urapidil on hemodynamic, metabolic and respiratory parameters in hypertensive patients with pulmonary edema. Intensive Care Med. 1998 June;24(6):557–63. https://doi.org/10.1007/s001340050615
32. (February 2, 2023). https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/018716s026lbl.pdf
33. (February 2, 2023). https://halmed.hr/upl/lijekovi/PIL/Lotan-PIL.pdf
34. (February 2, 2023). https://halmed.hr/upl/lijekovi/PIL/Tinidil-5-mg-sublingvalne-tablete-PIL.pdf
35. Cannon CM, Levy P, Baumann BM, Borczuk P, Chandra A, Cline DM, et al. Intravenous nicardipine and labetalol use in hypertensive patients with signs or symptoms suggestive of end-organ damage in the emergency department: a subgroup analysis of the CLUE trial. BMJ Open. 2013 March 26;3(3):e002338. https://doi.org/10.1136/bmjopen-2012-002338
36. Malik MA, Ahmad R, Beg M, Ahmad R. A comparative study of intravenous labetalol VS intravenous nitroglycerin in the treatment of hypertensive crises. Indian Heart J. 2022 July-August;74(4):332–4. https://doi.org/10.1016/j.ihj.2022.06.001
37. Shekhar S, Sharma C, Thakur S, Verma S. Oral nifedipine or intravenous labetalol for hypertensive emergency in pregnancy: a randomized controlled trial. Obstet Gynecol. 2013 November;122(5):1057–63. https://doi.org/10.1097/AOG.0b013e3182a9ea68
38. Muzzi DA, Black S, Losasso TJ, Cucchiara RF. Labetalol and esmolol in the control of hypertension after intracranial surgery. Anesth Analg. 1990 Jan;70(1):68-71. https://pubmed.ncbi.nlm.nih.gov/1967515/
39. Alijotas-Reig J, Bove-Farre I, de Cabo-Frances F, Angles-Coll R. Effectiveness and safety of prehospital urapidil for hypertensive emergencies. Am J Emerg Med. 2001 March;19(2):130–3. https://doi.org/10.1053/ajem.2001.20008
40. Salkic S, Brkic S, Batic-Mujanovic O, Ljuca F, Karabasic A, Mustafic S. Emergency Room Treatment of Hypertensive Crises. Med Arch. 2015 October;69(5):302–6. https://doi.org/10.5455/medarh.2015.69.302-306
41. Shi J, Li Y, Xing C, Peng P, Shi H, Ding H, et al. Urapidil, compared to nitroglycerin, has better clinical safety in the treatment of hypertensive patients with acute heart failure: a meta-analysis. Drug Des Devel Ther. 2018 December 27;13:161–72. https://doi.org/10.2147/DDDT.S185972
42. Željković Vrkić T, Prkačin I, Jelaković B. Hipertenzivna kriza. Medix. 2018;24(130/131):218–26.
43. Simić A, Nesek Adam V, Lukačević M A Arterial hypertension in outpatient emergency practice – retrospective analysis of hypertensive patients at the Emergency Medicine Department of Varaždin County]. Cardiol Croat. 2017;12(3):64. Croatian. https://doi.org/10.15836/ccar2017.64
44. Raos D, Paštrović F, Okštajner PK, Vodanović M, Prkačin I. Evaluation of hypertensive urgency management in out-of-hospital unit. Acta Med Croatica. 2020;74 Suppl 1:41–4. https://hrcak.srce.hr/236569