Automated analysis of finger blood pressure recordings provides insight in determinants of baroreflex sensitivity and heart rate variability-the HELIUS study.

Sympathovagal balance is important in the pathogenesis of hypertension and independently associated with mortality. We evaluated the value of automated analysis of cross-correlation baroreflex sensitivity (xBRS) and heart rate variability (HRV) and its relationship with clinical covariates in 13,326 participants from the multi-ethnic HELIUS study. Finger blood pressure (BP) was continuously recorded, from which xBRS, standard deviation of normal-to-normal intervals (SDNN), and squared root of mean squared successive difference between normal-to-normal intervals (RMSDD) were determined. A subset of 3356 recordings > 300 s was used to derive the minimally required duration by comparing shortened to complete recordings, defined as intraclass correlation (ICC) > 0.90. For xBRS and SDNN, 120 s and 180 s were required (ICC 0.93); for RMSDD, 60 s (ICC 0.94) was sufficient. We included 10,252 participants (median age 46 years, 54% women) with a recording > 180 s for the regression. xBRS, SDNN, and RMSDD decreased linearly up to 50 years of age. For xBRS, there was a signification interaction with sex, with for every 10 years a decrease of 4.3 ms/mmHg (95%CI 4.0-4.6) for men and 5.9 ms/mmHg (95%CI 5.6-6.1) for women. Using splines, we observed sex-dependent nonlinearities in the relation with BP, waist-to-hip-ratio, and body mass index. Future studies can help unravel the dynamics of these relations and assess their predictive value. Panel 1 depicts automatic analysis and filtering of finger BP recordings, panel 2 depicts computation of xBRS from interpolated beat to beat data of systolic BP and interbeat interval, and (IBI) SDNN and RMSDD are computed directly from the filtered IBI dataset. Panel 3 depicts the results of large-scale analysis and relation of xBRS with age, sex, blood pressure and body mass index.

Metabolic acidosis caused by concomitant use of paracetamol (acetaminophen) and flucloxacillin? A case report and a retrospective study.

PURPOSE: A patient was identified with severe metabolic acidosis, a high anion gap and 5-oxoproline accumulation, probably caused by the simultaneous use of paracetamol (acetaminophen) and flucloxacillin. We wanted to investigate the necessity to control the interaction between both drugs with an automatic alert system. METHODS: To investigate the relevance of the interaction of paracetamol and flucloxacillin, a retrospective study was conducted. Data on paracetamol and flucloxacillin prescriptions and laboratory data (pH, Na+, HCO3-, Cl-, albumin and 5-oxoproline levels) were combined to assess the prevalence of acidosis, calculate the anion gap and analyse 5-oxoproline levels in clinically admitted patients using both drugs simultaneously. RESULTS: In the 2-year study period, approximately 53,000 admissions took place in our hospital. One thousand and fifty-seven patients used paracetamol and flucloxacillin simultaneously, of which 51 patients (4.8%) had a serum pH ≤ 7.35. One patient, the same patient as presented in the case report, had a high anion gap and a toxic level of 5-oxoproline. CONCLUSION: The prevalence of metabolic acidosis is very low and the only patient identified with the interaction was recognised during normal clinical care. We conclude that automatic alerts based on simultaneous use of paracetamol and flucloxacillin will generate too many signals. To recognise patients earlier and prevent severe outcomes, a warning system (clinical rule) based on paracetamol, flucloxacillin and pH measurement may be helpful. Early calculation of the anion gap can narrow the differential diagnosis of patients with metabolic acidosis and measurement of 5-oxoproline can explain acidosis due the interaction of paracetamol and flucloxacillin.

Orthostatic Hypotension in Parkinson's Disease: The Relation of Blood Pressure Tests and Symptoms in Daily Life.

BACKGROUND: Orthostatic hypotension (OH) is common in Parkinson's disease (PD), but the relation between the results of orthostatic blood pressure tests and orthostatic symptoms in daily life is not clear. METHODS: We performed a cross-sectional study in an incident nontertiary care cohort of PD patients with additional recruitment of PD patients from our own outpatient clinic. We recruited sex- and age-matched controls. All participants underwent orthostatic blood pressure tests using continuous blood pressure measurements. Orthostatic symptoms experienced in daily life were assessed using autonomic symptom questionnaires (SCOPA-AUT and COMPASS-31). RESULTS: A total of 83 PD patients and 35 controls were included. Mean patient age was 69.2 years (standard deviation [SD]: 10.0). Mean disease duration was 6.6 years (SD, 0.8). The estimated prevalence of OH in PD was 24.1% (95% confidence interval: 16.2-34.3). There was no significant difference between PD patients with and without OH regarding reported daily orthostatic symptoms. Alternative OH criteria did not substantially improve this. CONCLUSIONS: Perceived orthostatic symptoms in daily life have no clear association with the results of a single orthostatic blood pressure test. Better diagnostic strategies are needed.

Initial orthostatic hypotension in teenagers and young adults.

OBJECTIVE: To assess: (1) the frequency of an abnormally large fall in blood pressure (BP) upon standing from supine in patients with initial orthostatic hypotension (IOH); (2) the underlying hemodynamic mechanisms of this fall in BP upon standing from supine and from squatting. METHODS: In a retrospective study of 371 patients (≤30 years) visiting the syncope unit, the hemodynamic response to standing and squatting were studied in 26 patients who were diagnosed clinically with IOH, based on history taking only. In six patients changes in cardiac output (CO) and systemic vascular resistance (SVR) were determined, and the underlying hemodynamics were analyzed. RESULTS: 15/26 (58 %) patients with IOH had an abnormally large initial fall in systolic BP (≥40 mmHg). There was a large scatter in CO and SVR response after arising from supine [ΔCO at BP nadir median -8 % (range -37, +27 %); ΔSVR at BP nadir median -31 % (range -46, +10 %)]. The hemodynamic response after squatting showed a more consistent pattern, with a fall in SVR in all six patients [ΔCO at BP nadir median +23 % (range -12, +31 %); ΔSVR at BP nadir median -42 %, (range -52, -35 %)]. INTERPRETATION: The clinical diagnosis of IOH is based on history taking, as an abnormally large fall in systolic BP can only be documented in 58 %. For IOH upon standing after supine rest, the hemodynamic mechanism can be either a large fall in CO or in SVR. For IOH upon arising from squatting a large fall in SVR is a consistent finding.

Treatment efficacy of hypertension in kidney transplant recipients in the Netherlands.

BACKGROUND: Hypertension in kidney transplant recipients jeopardises graft and patient survival. Guidelines suggest blood pressure targets of ≤130/80 mmHg and sodium intake <90 mmol/day. METHODS: Since the efficacy of antihypertensive treatment among kidney transplant recipients is unknown, we analysed data on office-based blood pressure and use of antihypertensive drugs from the Netherlands Organ Transplant Registry on 5415 kidney transplant recipients. Additionally, we studied dosages, prevalence of treatment-resistant hypertension and 24-hour sodium excretion in 534 kidney transplant recipients from our centre to explore possibilities for therapy optimisation. RESULTS: In patients registered in the Netherlands Organ Transplant Registry, median blood pressure was 134/80 mmHg (interquartile range 122-145/70-85). In 77.2%, the blood pressure was ≥130/80 mmHg; of these patients 10.4% had no registered use, 30.0% used one and 25.9% used ≥3 classes of antihypertensive agents. Parameters from our centre were comparable: 78.7% had a median blood pressure of ≥130/80 mmHg of whom 14.5% had no registered use of antihypertensives and 26.4% used ≥3 classes. Sub-maximal dosages were prescribed in 74.0% of the kidney transplant recipients with a blood pressure of ≥130/80 mmHg while using at least one antihypertensive agent. Treatment-resistant hypertension was present in 7.7%. Median 24-hour sodium excretion was 147 mmol/day (interquartile range 109-195). CONCLUSIONS: This study suggests that therapeutic optimisation of antihypertensive treatment in kidney transplant recipients is, in theory, frequently possible by intensifying pharmacological treatment and by providing more advice on dietary sodium restrictions.

At the heart of the arterial baroreflex: a physiological basis for a new classification of carotid sinus hypersensitivity.

The aim of this review is to provide an update of the current knowledge of the physiological mechanisms underlying reflex syncope. Carotid sinus syncope will be used as the classical example of an autonomic reflex with relatively well-established afferent, central and efferent pathways. These pathways, as well as the pathophysiology of carotid sinus hypersensitivity (CSH) and the haemodynamic effects of cardiac standstill and vasodilatation will be discussed. We will demonstrate that continuous recordings of arterial pressure provide a better understanding of the cardiovascular mechanisms mediating arterial hypotension and cerebral hypoperfusion in patients with reflex syncope. Finally we will demonstrate that the current criteria to diagnose CSH are too lenient and that the conventional classification of carotid sinus syncope as cardioinhibitory, mixed and vasodepressor subtypes should be revised because isolated cardioinhibitory CSH (asystole without a fall in arterial pressure) does not occur. Instead, we suggest that all patients with CSH should be thought of as being 'mixed', between cardioinhibition and vasodepression. The proposed stricter set of criteria for CSH should be evaluated in future studies.

Orthostatic leg blood volume changes assessed by near-infrared spectroscopy.

Standing up shifts blood to dependent parts of the body, and blood vessels in the leg become filled. The orthostatic blood volume accumulation in the small vessels is relatively unknown, although these may contribute significantly. We hypothesized that in healthy humans exposed to the upright posture, volume accumulation in small blood vessels contributes significantly to the total fluid volume accumulated in the legs. Considering that near-infrared spectroscopy (NIRS) tracks postural blood volume changes within the small blood vessels of the lower leg, we evaluated the NIRS-determined changes in oxygenated (Δ[O(2)Hb]), deoxygenated (Δ[HHb]) and total haemoglobin tissue concentration (Δ[tHb]) and in total leg volume by strain-gauge plethysmography during 70 deg head-up tilt (HUT; n = 7). In a second experiment, spatial and temporal reproducibility were evaluated with three NIRS probes applied on two separate days (n = 8). In response to HUT, an initially fast increase in [O(2)Hb] was followed by a gradual decline, while [HHb] increased continuously. The increase in [tHb] during HUT was closely related to the increase in total leg volume (r(2) = 0.95 ± 0.03). After tilt back, [O(2)Hb] declined below and [HHb] remained above baseline, whereas all NIRS signals gradually returned to baseline. Spatial heterogeneity was observed, and for two probes [tHb] was highly correlated between days (r(2) = 0.92 ± 0.09 and 0.91 ± 0.12), but less for the third probe (r(2) = 0.44 ± 0.36). The results suggest a non-linear accumulation of blood volume in the small vessels of the leg, with an initial fast phase followed by a more gradual increase at least partly contributing to the relocation of fluid during orthostatic stress.

[Hypoglycaemia unawareness: report it to the CBR (the Dutch Driving Test Organisation) and revoke the licence to drive]. / Hypoglycemia unawareness: meld het bij het CBR.

The Dutch legislator has adopted the point of view that people with diabetes and hypoglycaemia unawareness are unfit for driving a motor vehicle because hypoglycaemia unawareness carries with it an unacceptable risk for traffic accidents. There is no legal obligation for people in possession of a driving license to report changes to their state of health such as the appearance of hypoglycaemia unawareness. We argue that patients with newly diagnosed diabetes should inform the Driving Test Organisation about changes to their health status for moral reasons, and for reasons of judicial liability. This subject should be included in patient education, as should be strategies to minimise the risk of hypoglycaemia. In exceptional cases, the physician may opt to breech medical confidentiality and report the presence of hypoglycaemia unawareness in order to avert immediate, severe danger.

The history of diagnosing carotid sinus hypersensitivity: why are the current criteria too sensitive?

The carotid sinus syndrome and carotid sinus hypersensitivity (CSH) are closely related disorders. The first is characterized by syncope triggered by manipulation of the carotid sinus in daily life (e.g. shaving). According to the current European Society of Cardiology guidelines, CSH is diagnosed when carotid sinus massage elicits ≥3 s asystole, a fall in systolic blood pressure of ≥50 mmHg, or both, with symptoms. The question is, however, whether symptoms can be expected when these criteria are met. Although they are widely accepted, we will show that their basis is primarily in arbitrary clinical observations and that in the original publications the link between classification and clinical symptoms was often dubious. The current criteria for CSH are thus too sensitive, explaining the reported high prevalence of CSH in the general older population. The review will conclude with suggesting a stricter set of criteria for CSH that should be evaluated in future studies.

[To resuscitate or not? Discuss timely with all chronically ill patients]. / Reanimeren of niet? Bespreek dit tijdig met iedere chronisch zieke patiënt.

In-hospital adult cardiopulmonary resuscitation is successful in only approximately 20% of cases and may result in permanent neurological damage. Two reasons justify not commencing resuscitation: either the patient does not want to be resuscitated, or resuscitation is considered medically futile by the doctor. This subject should be discussed timely with all chronically ill patients who are likely to be admitted to hospital, preferably in the outpatient clinic setting, and results must be communicated with all doctors involved (e.g. general practitioners). Here we describe 3 cases that demonstrate the need to discuss possible restrictions on cardiopulmonary resuscitation with all chronically ill patients, regardless of their age. The first was a 45-year-old HIV-positive male with chronic clinical depression who refused ICU care, the second a 75-year-old patient whose initial 'do no resuscitate' order was reversed based on the wishes of her daughter and the third a 45-year-old female with sickle cell disease who expressed a sustained wish not to be treated in the ICU or to be resuscitated.

Vasovagal syncope interrupting sleep?

Clinical data are reported for 13 patients who were referred with recurrent loss of consciousness at night interrupting their sleep. Most of the patients were women (10 of 13) with a mean age of 45 years (range 21-72 years). The histories were more consistent with vasovagal syncope than with epilepsy. This was supported by electroencephalographic and tilt test results. More polysomnographic monitoring data are required to confirm the diagnosis of vasovagal syncope interrupting sleep. This will be difficult because, although the condition may not be rare, the episodes are usually sporadic.

[Initial diagnostic strategy in the case of transient losses of consciousness: the importance of the medical history]. / Initiële diagnostische strategie bij wegrakingen: het belang van de anamnese.

It is estimated that almost half of the people experience a transient loss of consciousness at some time during their life. In young patients (< 35 years) the cause is mostly a reflex syncope. In older patients the common causes are orthostatic and postprandial hypotension, sinus caroticus syndrome, cardiac arrhythmias and valvular disorders. The medical history can identify a probable cause of the transient loss of consciousness in almost all young patients (< 35 years) and in the majority of older patients. A physical examination and an ECG should be performed in all patients who have experienced a transient loss of consciousness, other than those with classical vasovagal syncope, in order to exclude orthostatic hypotension and dangerous cardiac causes.