Characteristics, practice patterns, and outcomes in patients with acute hypertension: European registry for Studying the Treatment of Acute hyperTension (Euro-STAT)
© Vuylsteke et al.; licensee BioMed Central Ltd. 2011
Received: 29 July 2011
Accepted: 16 November 2011
Published: 16 November 2011
Although effective strategies are available for the management of chronic hypertension, less is known about treating patients with acute, severe elevations in blood pressure. Using data from the European registry for Studying the Treatment of Acute hyperTension (Euro-STAT), we sought to evaluate 'real-life' management practices and outcomes in patients who received intravenous antihypertensive therapy to treat an episode of acute hypertension.
Euro-STAT is a European, hospital-based, observational study of consecutive adult patients treated with intravenous antihypertensive therapy while in the emergency department, perioperative unit or ICU. Enrolment took place between 1 July and 15 October 2009 in 11 hospitals in 7 European countries (Austria, Belgium, Germany, Italy, Spain, Sweden and the United Kingdom).
The study population was composed of 791 consecutive patients (median age 69 years, 37% women). Median arterial blood pressure before treatment was 166 mmHg systolic blood pressure (IQR 141 to 190 mmHg) and 80 mmHg diastolic blood pressure (IQR 68 to 95). Nitroglycerine was the most commonly used antihypertensive treatment overall (40% of patients), followed by urapidil (21%), clonidine (16%) and furosemide (8%). Treatment was associated with hypotension in almost 10% of patients. Overall 30-day mortality was 4%, and new or worsening end-organ damage occurred in 19% of patients.
High blood pressure requiring intravenous therapy is currently managed with a variety of agents in Europe, with those most commonly used being nitroglycerine, urapidil and clonidine. Patients with acute hypertension have substantial concomitant morbidity and mortality, and intravenous antihypertensive treatment is associated with hypotension in almost 10% of cases.
Over 1 billion people worldwide are estimated to have hypertension [1, 2], which increases their risk of cardiovascular morbidity and mortality [3, 4] and organ injury [5, 6]. One percent of all hypertensive patients experience at least one episode of acute, severe hypertension, necessitating intravenous (IV) antihypertensive therapy and placing these patients at risk of overt, acute end-organ damage over their lifetime. The actual prevalence may in fact be much higher [7, 8]. One-fourth of patients who present to busy emergency departments (EDs) have acute, severe hypertension [7, 8]. In the present study, we defined this population by using a pragmatic approach according to whether the treating physicians decided to use IV antihypertensive therapy.
Multiple effective strategies are used for the management of chronic hypertension , but less is known about treating patients who present with acute, severe elevations in arterial blood pressure (BP). The optimal target for BP lowering has yet to be defined; the definitions of hypertensive urgencies, emergencies and outcome measures lack uniformity; evidence supporting the use of one drug over another is lacking; and whether certain treatments are better than others is unknown . As a consequence, treatment practices vary . The European registry for Studying the Treatment of Acute hyperTension (Euro-STAT) was conducted to evaluate 'real-life' management practices and outcomes in patients treated with IV antihypertensive therapy for an episode of acute hypertension.
Euro-STAT is a European, hospital-based, observational study of consecutive patients treated with IV antihypertensive therapy while in the critical care setting. Enrolment took place between 1 July and 15 October 2009 in 11 hospitals in 7 European countries (Austria, Belgium, Germany, Italy, Spain, Sweden and the United Kingdom).
Sites and investigators participating in Euro-STAT
AKH General Hospital
Michael J Hiesmayr
Erasme University Hospital
Università degli Studi di Firenze
A Raffaele De Gaudio
Salvatore Di Somma
Hospital de Sabadell
Karolinska Universitetssjukhuset, Solna
New Cross Hospital Wolverhampton
Papworth Hospital NHS Trust
Southampton General Hospital
The objectives of the registry were (1) to improve the understanding of the characteristics of patients with acute BP elevation cared for in EDs, perioperative units and ICUs; (2) to describe contemporary IV management practices, including the timing of treatment initiation, medications used to control BP within selected ranges and the time required to achieve BP control; and (3) to determine in-hospital and postdischarge outcomes as they relate to the management of an episode of acute hypertension. A preliminary goal was to establish the rates of key variables, which could then be used to develop formal sample size estimates for a planned larger study in the same setting.
Patient selection and enrolment criteria
Consecutive adult male and female patients at least 18 years of age with a qualifying episode of acute hypertension on or after 1 July 2009 were identified by trained data abstractors through prospective identification of patients admitted to EDs, perioperative units and ICUs. To qualify for enrolment, a patient had to meet the following two criteria: (1) The clinician had to have attempted BP control with either an IV infusion or at least two IV boluses of an antihypertensive drug, and (2) the initial treatment had to have been started within 24 hours of the patient's arrival in the ED, at any time during the perioperative period (defined as the time from the initiation of anaesthesia to discharge from the postanaesthesia recovery area) or within 14 days of ICU admission.
Patients were excluded from participating in the study if they had received IV antihypertensive treatment initiated in a transferring hospital, if they were admitted for burn treatment, if they had drug-induced (iatrogenic) hypertension, if the qualifying event had occurred while being treated with comfort measures only, and if medical records were not available. ED patients were excluded if they were transferred directly from the ED to another healthcare facility after initiation of IV antihypertensive treatment. Perioperative patients were excluded if they had planned perioperative controlled hypotension and if the qualifying event occurred before the induction of anaesthesia.
All eligible patients were assigned a unique study identification number, and abstractors completed a standardised case report form that had been piloted and subsequently validated. Data were abstracted from hospital medical records.
The main clinical outcome measures were all-cause in-hospital mortality, end-organ injury (including ischaemic stroke, encephalopathy (defined as acute mental status changes without other identifiable causes), acute coronary syndrome, congestive heart failure, renal insufficiency ('chronic kidney failure' was defined as previously diagnosed renal insufficiency or documentation of creatinine clearance less than 60 ml/minute before admission) and aortic dissection), and survival at 30 days following hospital discharge.
Data quality and management
Training material and guidelines for data abstractors were developed by the data-coordinating centre at the Center for Outcomes Research (COR) at the University of Massachusetts Medical School (Worcester, MA, USA). A one-day course was held at each enrolling hospital to maintain common definitions, improve data abstraction and address training needs.
Data were collected, handled and analysed independently of the sponsor by the data-coordinating centre. Study coordinators at COR reviewed the data collection forms to identify variances from norms and missing data and followed up with the principal investigators by mail or by telephone to resolve any queries.
Descriptive statistics were calculated for all patients. Data are summarised as means (± SD) or as medians (25% and 75% percentiles) for continuous data and as counts and percentages for categorical data. All results shown are univariate and unadjusted. No variable had a level of missing data greater than 10%. Any missing data were simply excluded from the analyses. All eligible patients underwent chart review, and there was no loss to follow-up. Patients' charts were reviewed until the patient's death or discharge from the hospital up to 30 days after initiation of IV antihypertensive therapy (whichever came first). Statistical analyses were performed using the SAS version 9.2 software package (SAS Institute, Cary, NC, USA).
Overview of study population
Baseline characteristics of the study population
Median age, years (IQR)
69 (58 to 77)
70 (60 to 79)
69 (59 to 76)
66 (53 to 76)
Females, n (%)
Medical history, n (%)
Hospitalisation for hypertension
Chronic kidney disease
End-stage renal disease
Neurological dysfunction or disease
Peripheral vascular disease
Alcohol misuse (≥2 drinks/day)
Drug abuse (amphetamines, cocaine, other)
Predisposing factors, n (%)
Medication nonadherence (ED)
Medications withheld > 12 hours (ICU and perioperative)
Blood pressure, laboratory values, end-organ damage and outcomes (in-hospital)
ED (n= 180)
ICU (n= 382)
Perioperative (n= 229)
Median blood pressure, mmHg (IQR)
166 (141 to 190)
200 (174 to 220)
160 (138 to 180)
160 (140 to 180)
80 (68 to 95)
100 (90 to 110)
73 (64 to 85)
80 (68 to 90)
Median time from qualifying BP to initiation of IV antihypertensive therapy, minutes (IQR)
5.0 (2.0 to 17)
20 (5.0 to 30)
5.0 (1.0 to 15)
5.0 (1.0 to 5.0)
Median time from IV initiation to 10% decrease in SBP, minutes (IQR)
28 (11 to 60)
31 (18 to 87)
30 (12 to 70)
18 (8.0 to 43)
Median laboratory values (IQR)
0.03 (0.01 to 0.23)
0.03 (0.01 to 0.12)
0.04 (0.01 to 0.33)
0.03 (0.01 to 0.23)
Peak creatine kinase-MB
33 (9.4 to 88)
5.1 (3.8 to 78)
50 (31 to 152)
38 (24 to 79)
910 (295 to 2, 240)
1, 672 (429 to 2, 637)
1, 451 (428 to 2, 709)
359 (242 to 970)
99 (82 to 132)
116 (91 to 146)
20 (20 to 20)
Initial creatinine, μmol/L
89 (72 to 113)
94 (78 to 125)
91 (74 to 116)
83 (69 to 102)
Peak creatinine, μmol/L
103 (82 to 146)
119 (99 to 222)
107 (84 to 151)
92 (73 to 122)
End-organ injurya, n (%)
Acute coronary syndrome (new)
Acute LV dysfunction/pulmonary oedema (new)
Aortic dissection (new)
Acute kidney failure (new)
Outcomes n (%)
Intravenous antihypertensive drugs
In each group, more than 90% of patients achieved a 10% decrease in SBP within the first 72 hours following initiation of IV antihypertensive therapy. The median time to 10% decrease was 28 minutes after starting the antihypertensive drug. The following is the breakdown of patients who did not achieve a 10% decrease within 72 hours: 6 of 180 ED patients (3.3%), 22 of 382 ICU patients (5.8%) and 8 of 229 perioperative patients (3.5%).
Emergency department patients
The median (IQR) number of hours in the ED was 8.0 (4.0 to 20), the minimum ED stay was one-half hour and the maximum stay was 144 hours. Most ED patients (n = 155, 95%) had their IV antihypertensive treatment started in the ED; 9 patients (5.5%) had it started in the ambulance; 4.4% experienced an episode of hypotension requiring discontinuation of the antihypertensive drug, and/or the administration of vasopressors or fluids, or reverse Trendelenburg positioning within 72 hours of starting treatment; and 3.3% relapsed (requiring resumption of IV antihypertensive treatment) within 72 hours of discontinuation of the initial IV treatment.
The majority of the ED patients were admitted to a non-ICU inpatient unit (n = 104, 58%). Fifty-three patients (29%) were discharged to home, 16 (8.9%) were admitted to the ICU, 5 (2.8%) left against medical advice and 2 (1.1%) died in the ED.
The preoperative diagnoses of the 229 perioperative patients are shown in Figure 2B. Most operating or recovery room patients had undergone cardiac (40%), gastrointestinal (17%), orthopaedic (11%) or vascular (9.2%) surgery. The median duration of surgery was 190 minutes. Nearly one-half of the patients (n = 112, 49%) had undergone cardiac surgery and were evaluated on the basis of their EuroSCORE (European System for Cardiac Operative Risk Evaluation; available at http://www.euroscore.org/). The median score (IQR) was 2.5 (1.2 to 6.4; minimum 0, maximum 68.6), which is equivalent to a median predicted mortality rate of 2.5% (1.2% to 6.4%). For most patients (n = 143, 67%) IV antihypertensive treatment started in the operating room or theatre, and in 33% (n = 71) it was begun after surgery. Postoperatively, 57% (n = 130) of the patients were transferred to a postanaesthesia recovery area, 31% (n = 72) were transferred directly to the ICU and 12% (n = 27) were transferred directly to an inpatient ward or unit. Ten percent of patients experienced an episode of hypotension within 72 hours of starting treatment, and 4.8% of patients relapsed within 72 hours of the discontinuation of the initial IV treatment. Thirty-nine percent (n = 89) of patients received two or more different IV antihypertensive drugs.
Most ICU patients (304 of 382, 80%) were direct postoperative admissions (that is, patients whose initial acute, severe hypertension developed after ICU admission). Their primary diagnoses are shown in Figure 2C. The majority of patients in the ICU population were cardiac or cardiac surgery patients (62%), 25% were mixed surgical and medical patients, 7% were surgical patients, 4% were medical patients and 3% were classified as 'other'. Patients spent a median (IQR) of 3 days (2 to 6) in the ICU. Among ICU patients, the minimum stay was 1 day and the maximum stay was 54 days. Thirteen patients (3.4%) died in the ICU. The median time (IQR) in the ICU before IV treatment began was 3.4 hours (0.6 to 18). Overall, 8.4% of ICU patients experienced an episode of hypotension within 72 hours of the start of IV antihypertensive treatment, 6.0% relapsed within 72 hours of discontinuation of the initial IV treatment, and 17% required treatment with more than one agent. Upon discharge, 90% (n = 343) of the patients were transferred to an inpatient unit, 3.7% (n = 14) were transferred to another healthcare facility, 2.9% (n = 11) were discharged to home and 0.3% (n = 1) left against medical advice.
The overall rate of 30-day death rate was 4%, and the overall rate of new or worsening end-organ damage was 19%. The rates of both outcomes were highest among patients in the ED (6% and 43%, respectively), intermediate in the ICU patients (5% and 15%, respectively) and lowest among patients in the perioperative setting (2% and 7%, respectively).
These contemporary data derived from the Euro-STAT study demonstrate heterogeneous patterns of care for patients presenting with acute elevation of BP across a range of acute care settings, with high rates of morbidity and mortality. Of the 791 patients included in Euro-STAT, 48% were treated for acute hypertension in the ICU. Many of them had undergone surgery and developed severe hypertension postoperatively, 29% developed it perioperatively and 23% developed it in the ED. Median BP was higher among patients treated in the ED (200/100 mmHg) than in those treated in the ICU (160/73 mmHg) or perioperatively (160/80 mmHg).
The Studying the Treatment of Acute Hypertension (STAT) registry in the United States [9, 10] involved patients with a qualifying episode of acute, severe hypertension (that is, (1) SBP greater than 180 and/or DBP greater than 110 mmHg or (2) SBP above 140 mmHg and/or DBP greater than 90 mmHg when presenting with subarachnoid haemorrhage) who received IV antihypertensive therapy in a critical care setting. Compared with the STAT study, the patients' median age in the Euro-STAT study was higher (69 vs 58 years) and fewer patients had a history of hypertension (62% vs 89%). Overall, the median BP was lower in the Euro-STAT study than in the STAT study (166/80 vs 200/110 mmHg). This finding could indicate that patients in the Euro-STAT study had less severe hypertension, or it could be related to the different qualifying criteria and hence the distribution of patients in the STAT studies. In Euro-STAT, perioperative patients were also included, and there were many more ICU patients (mainly in a postoperative context) than there were in the STAT study.
The decision to amalgamate ED, perioperative and ICU patients was made because the purpose of this descriptive study was to evaluate the efficacy of IV therapy for the control of elevated BP level in different locations within a hospital, thereby assessing similarities and differences in treatments and outcomes in different contexts.
The first antihypertensive drug used varied by treatment location. In the ICU, nitroglycerine was by far the most widely used (60%); in the ED, furosemide was used in 34% of patients and nitroglycerine was used in 27%; and perioperatively, urapidil was used in 34% of patients and clonidine was used in 28%. The high use of furosemide in the ED (34%) indicates that pulmonary oedema associated with high BP was the likely primary diagnosis, which is backed up by the higher rates of new or worsened acute coronary syndrome (17% vs 1.1% and 0.5%) and acute left ventricular dysfunction (19.4% vs 2.9% and 0.9%) in ED vs ICU and perioperative patients, respectively. In Euro-STAT overall, the most frequently used antihypertensive drugs were nitroglycerine (40%), urapidil (21%), clonidine (16%) and furosemide (8.3%). This pattern is very different from the results of the STAT study, where the most common initial antihypertensive drugs were labetalol (32%), metoprolol (17%), nitroglycerine (15%) and hydralazine (15%) . The variations in drug use between the Euro-STAT and STAT studies may reflect differences in the drugs available in these regions. The percentage of patients who required a second IV antihypertensive was 34% in both the Euro-STAT and STAT studies.
Recommended treatments for hypertensive emergenciesa
Pulmonary oedema + systolic dysfunction
Pulmonary oedema + diastolic dysfunction
While nitroglycerine should be used as an adjunctive therapy, the high rates of use in the Euro-STAT population likely reflect familiarity with its use, together with its ease of administration, titration and rapid reversibility. In the ED, the ICU and perioperatively, 4.4%, 8.4% and 10% of patients, respectively, had hypotension within 72 hours of the start of treatment, resulting in (1) discontinuation of the antihypertensive drug or (2) treatment with vasopressors, fluids or reverse Trendelenburg positioning. The overall incidence of hypotension in the Euro-STAT study was higher than that in the STAT study (8.1% vs 4.0%) .
As expected, mortality rates at discharge from the ICU, ED or surgical department in the Euro-STAT study were highest among ICU patients (3.4% vs 1.1% of ED patients and 0% of perioperative patients). Total in-hospital mortality in the Euro-STAT study was highest among ED patients (5.7% vs 5.1% of ICU patients and 2.3% of perioperative patients), which is lower than the comparable rate in the STAT study (6.9%) . New or worsened end-organ damage was observed in 43% of ED patients, 15% of ICU patients and 6.6% of perioperative patients.
The observational Euro-STAT registry is a relatively small data set, and the sites may not be representative of all hospitals in Europe. Treatment choices may therefore be biased by institution choices. Also, populations of acute hypertension are heterogeneous and are likely to differ by country. Amalgamation of all countries into one data set therefore gives an overview, but no country-specific data. As our entry criteria required the physician to initiate IV antihypertensive therapy, there was no comparison with other patients in relation to morbidity. Also, we do not have complete information on post-hospital discharge follow-up. Furthermore, we do not know what happened to patients for whom a reduction in BP was not achieved despite treatment.
Acute hypertension is currently managed with a wide range of IV agents in the various clinical settings in which it arises. These patients have substantial concomitant morbidity and mortality, and IV antihypertensive treatment is associated with hypotension in almost 10% of patients. Further data are required to identify optimal management strategies for these patients, thereby ensuring the best possible outcomes.
High blood pressure requiring intravenously administered drug therapy is currently managed with a variety of agents in Europe, with the most commonly used being nitroglycerine, urapidil and clonidine.
Intravenous antihypertensive treatment is associated with hypotension in almost 10% of patients.
Patients with acute, severe hypertension have substantial concomitant morbidity and mortality.
Center for Outcomes Research
European registry for Studying the Treatment of Acute hyperTension.
We thank the physicians and study coordinators participating in Euro-STAT and the staff at COR.
Euro-STAT Steering Committee members
Co-Chairs: Didier Payen de la Garanderie, Paris, France; Alain Vuylsteke, Cambridge, UK. Members: Frederick A Anderson, Worcester, MA, USA; Antonio Artigas, Sabadell, Spain; Jean-Daniel Chiche, Paris, France; A Raffaele De Gaudio, Florence, Italy; Salvatore Di Somma, Rome, Italy; Joel M Gore, Worcester, MA, USA; Christopher B Granger, Durham, NC, USA; Michael J Hiesmayr, Vienna, Austria; Andreas Hoeft, Bonn, Germany; Bengt Jönsson, Stockholm, Sweden; Andreas Koster, Berlin, Germany; Thomas Lüscher, Zurich, Switzerland; Jan Ostergren, Stockholm, Sweden; W Frank Peacock, Cleveland, OH, USA; Kees Polderman, Utrecht, The Netherlands; David Smith, Southampton, UK; Jean-Louis Vincent, Brussels, Belgium.
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