Efficacy of postmortem CT and tissue sampling in establishing the cause of death in clinical practice: a prospective observational study.

AIMS: The aim of this study is to evaluate whether agreement with autopsy-determined cause of death (COD) increases by use of postmortem CT (PMCT) or PMCT in combination with postmortem sampling (PMS), when compared with clinical assessment only. METHODS: This prospective observational study included deceased patients from the intensive care unit and internal medicine wards between October 2013 and August 2017. The primary outcome was percentage agreement on COD between the reference standard (autopsy) and the alternative postmortem examinations (clinical assessment vs PMCT or PMCT+PMS). In addition, the COD of patient groups with and without conventional autopsy were compared with respect to involved organ systems and pathologies. RESULTS: Of 730 eligible cases, 144 could be included for analysis: 63 underwent PCMT without autopsy and 81 underwent both PMCT and autopsy. Agreement with autopsy-determined COD was significantly higher for both PMCT with PMS (42/57, 74%), and PMCT alone (53/81, 65%) than for clinical assessment (40/81, 51%; p=0.007 and p=0.03, respectively). The difference in agreement between PMCT with PMS and PMCT alone was not significant (p=0.13). The group with autopsy had a significantly higher prevalence of circulatory system involvement and perfusion disorders, and a lower prevalence of pulmonary system involvement. CONCLUSION: PMCT and PMS confer additional diagnostic value in establishing the COD. Shortcomings in detecting vascular occlusions and perfusion disorders and susceptibility to pulmonary postmortem changes could in future be improved by additional techniques. Both PMCT and PMS are feasible in clinical practice and an alternative when autopsy cannot be performed.

A Systematic Review of Methods for Medical Record Analysis to Detect Adverse Events in Hospitalized Patients.

OBJECTIVE: In this systematic review, we evaluate 2 of the most used trigger tools according to the criteria of the World Health Organization for evaluating methods. METHODS: We searched Embase, PubMed, and Cochrane databases for studies (2000-2017). Studies were included if medical record review (MRR) was performed with either the Global Trigger Tool or the Harvard Medical Practice Study in a hospital population. Quality assessment was performed in duplicate. Fifty studies were included, and results were reported for every criterion separately. RESULTS: Medical record review reveals more adverse events (AEs) than any other method. However, at the same time, it detects different AEs. The costs of an AE were on average €4296. Considerable efforts have been made worldwide in health care to improve safety and to reduce errors. These have resulted in some positive effects. The literature showed that MRR is focused on several domains of quality of care and seems suitable for both small and large cohorts. Furthermore, we found a moderate to substantial agreement for the presence of a trigger and a moderate to good agreement for the presence of an AE. CONCLUSIONS: Medical record review with a trigger tool is a reasonably well-researched method for the evaluation of the medical records for AEs. However, looking at the World Health Organization criteria, much research is still lacking or of moderate quality. Especially for the cost of detecting AEs, valuable information is missing. Moreover, knowledge of how MRR changes quality and safety of care should be evaluated.

The Harvard medical practice study trigger system performance in deceased patients.

BACKGROUND: To detect possible threats to quality and safety, multiple systems have been developed. One of them is retrospective chart review. A team of experts scrutinizes medical records, selected by trigger systems, to detect possible adverse events (AEs). The most important AEs and more hints for possible improvement of care appear in deceased patients. Using triggers in a sample of these patients might increase the performance and lower the burden of scrutinizing records without possible preventable AEs. The aim of this study was therefore to determine the performance of the trigger system in a sample of deceased patients and to calculate the specificity and the sensitivity of this trigger system for predicting AEs. METHODS: We performed a study in which the records of deceased patients were screened for triggers by a team of trained nurses. A sample of 100 medical records was randomly selected out of records which had been screened between 2012 and 2015 for the first time, prior to the study in 2016. For the determination of significant differences between the first and second screening, McNemar's test of symmetry was used. Also, observed agreement, Cohen's Kappa and prevalence-adjusted and-bias-adjusted-kappa (PABAK) statistics were calculated. This was done for the two trigger rounds on both any trigger present and for every trigger separately. RESULTS: The observed agreement for any given trigger was 75% with a Kappa and PABAK of 0.5. For the individual triggers, the observed agreement was on average 90%. The corresponding Kappa was on average 0.42 (range: - 0.03-0.78) and the average PABAK was 0.8 (range: 0.44-0.92). Two adverse events were found in cases without triggers previously. The recalculated specificity and sensitivity for the original population were 58 and 92% respectively. CONCLUSIONS: For the reproducibility of triggers it seems that some perform better than others, but on average this is to our opinion suboptimal. The low specificity implies that many records are selected without AEs. This leads to a high false-positive rate making this labour-intensive record review process costly. Therefore, research for better and more expedient systems is required.

Variación biológica de Creatinina, Cistatina C y Tasa de Filtrado Glomerular Estimada a lo largo de 24 horas / Biological Variation of Creatinine, Cystatin C, and Estimated Glomerular Filtration Rate over 24 hours

Antecedentes: La tasa de filtración glomerular estimada (TFGe) es ampliamente utilizada en la práctica clínica. El presente estudio evaluó la variación biológica intraindividual (CVI) de diferentes ecuaciones de TFGe en sujetos con enfermedad renal crónica (ERC) y sin ERC. Los objetivos de este estudio fueron (a) determinar los perfiles de variación biológica durante 24 horas de creatinina, cistatina C y TFGe y (b) determinar si el CVI de la creatinina, la cistatina C y la TFGe cambia el deterioro de la filtración glomerular. Métodos: Se analizaron muestras de sangre cada hora de 37 individuos (17 sin ERC, 20 con ERC) durante 24 h. La creatinina (método enzimático) y la cistatina C se midieron usando un Cobas 8000 (Roche Diagnostics). La TFGe se estimó utilizando la Modificación de la Dieta en la Enfermedad Renal y la Colaboración de Epidemiología de la Enfermedad Renal Crónica basada en creatinina y/o cistatina C. Las muestras de plasma se almacenaron a -80 °C antes del análisis. Se verificaron los análisis de valores atípicos y de homogeneidad antes de realizar un ANOVA anidado para determinar la variación biológica. Resultados: La CVI de creatinina fue más alta en sujetos sin ERC que en aquellos con ERC (6.4% frente a 2.5%) debido principalmente al efecto más marcado del consumo de carne sobre la variabilidad de creatinina en individuos con concentraciones iniciales de creatinina más bajas. A diferencia de la creatinina, las concentraciones de cistatina C no se vieron afectadas por el consumo de carne. La cistatina C mostró alguna variación rítmica diurna y menor en los sujetos con ERC. Los valores de referencia del cambio (VCR) de todas las ecuaciones de TFGe estuvieron dentro del 13% al 20% en ambos grupos de estudio. Conclusiones: A pesar de las diferencias en el CVI de la creatinina, el CVI y el VRC de las ecuaciones de TFGe fueron relativamente similares para los sujetos con o sin ERC.

Background: Estimated glomerular filtration rate (eGFR) is widely used in clinical practice. This study assessed the within-subject biological variation (CVI) of different eGFR equations in people with chronic kidney disease (CKD) and people without CKD. The aims of this study were (a) to determine the 24-h biological variation profiles of creatinine, cystatin C, and eGFR and (b) to determine whether CVI of creatinine, cystatin C, and eGFR changes on deterioration of glomerular filtration. Methods: Hourly blood samples were analyzed from 37 individuals (17 without CKD, 20 with CKD) during 24 h. Creatinine (enzymatic method) and cystatin C were measured using a Cobas 8000 (Roche Diagnostics). eGFR was estimated using the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration based on creatinine and/or cystatin C. Plasma samples were stored at -80 °C before analysis. Outlier and homogeneity analyses were checked before performing a nested ANOVA to determine biological variation. Results: CVI of creatinine was higher in people without CKD than in those with CKD (6.4% vs. 2.5%) owing primarily to the more profound effect of meat consumption on creatinine variability in individuals with lower baseline creatinine concentrations. Unlike creatinine, cystatin C concentrations were unaffected by meat consumption. Cystatin C showed some diurnal rhythmic variation and less in people with CKD. Reference change values (RCVs) of all eGFR equations were within 13% to 20% in both study groups. Conclusions: Despite differences in CVI of creatinine, the CVI and RCV of the eGFR equations were relatively similar for people with or without CKD.

Adverse event detection by medical record review is reproducible, but the assessment of their preventability is not.

OBJECTIVE: To assess the reproducibility of adverse event evaluation by a medical record review committee. DESIGN: Cross-sectional reanalysis of medical records. INTERVENTION: Reviewers re-examined fifty medical records of deceased patients regarding the presence of adverse events, their potential preventability and their possible contribution to death. Also we investigated the root causes of the preventable AEs. Differences between the first and second assessment were calculated. RESULTS: The Kappa on the presence of an adverse event was 0.64 and 0.32 for the potential preventability. The intrarater agreement showed a Kappa of 0.61 on the adverse event presence and 0.64 for the potential preventability. Interrater agreement showed a Kappa of 0.66 for the adverse event presence and 0.03 for the potential preventability. CONCLUSION: We found a fair reproducibility for the detection of adverse events, but a poor reproducibility for the potential preventability. Possibly this was caused by lack of a definition for the preventability of adverse events. We think giving feedback to professionals using the results of medical record review remains valuable, but an improvement of its reproducibility is essential. To our opinion an international consensus on what exactly constitutes preventability of adverse events and agreement on a definition is necessary. This would result in more comparable studies in this field and could then be more informative on the ideal procedure to avoid certain potentially preventable adverse events in the future.

Biological Variation of Creatinine, Cystatin C, and eGFR over 24 Hours.

BACKGROUND: Estimated glomerular filtration rate (eGFR) is widely used in clinical practice. This study assessed the within-subject biological variation (CVI) of different eGFR equations in people with chronic kidney disease (CKD) and people without CKD. The aims of this study were (a) to determine the 24-h biological variation profiles of creatinine, cystatin C, and eGFR and (b) to determine whether CVI of creatinine, cystatin C, and eGFR changes on deterioration of glomerular filtration. METHODS: Hourly blood samples were analyzed from 37 individuals (17 without CKD, 20 with CKD) during 24 h. Creatinine (enzymatic method) and cystatin C were measured using a Cobas 8000 (Roche Diagnostics). eGFR was estimated using the Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration based on creatinine and/or cystatin C. Plasma samples were stored at -80 °C before analysis. Outlier and homogeneity analyses were checked before performing a nested ANOVA to determine biological variation. RESULTS: CVI of creatinine was higher in people without CKD than in those with CKD (6.4% vs 2.5%) owing primarily to the more profound effect of meat consumption on creatinine variability in individuals with lower baseline creatinine concentrations. Unlike creatinine, cystatin C concentrations were unaffected by meat consumption. Cystatin C showed some diurnal rhythmic variation and less in people with CKD. Reference change values (RCVs) of all eGFR equations were within 13% to 20% in both study groups. CONCLUSIONS: Despite differences in CVI of creatinine, the CVI and RCV of the eGFR equations were relatively similar for people with or without CKD.

Informal learning from error in hospitals: what do we learn, how do we learn and how can informal learning be enhanced? A narrative review.

Learning from error is not just an individual endeavour. Organisations also learn from error. Hospitals provide many learning opportunities, which can be formal or informal. Informal learning from error in hospitals has not been researched in much depth so this narrative review focuses on five learning opportunities: morbidity and mortality conferences, incident reporting systems, patient claims and complaints, chart review and prospective risk analysis. For each of them we describe: (1) what can be learnt, categorised according to the seven CanMEDS competencies; (2) how it is possible to learn from them, analysed against a model of informal and incidental learning; and (3) how this learning can be enhanced. All CanMEDS competencies could be enhanced, but there was a particular focus on the roles of medical expert and manager. Informal learning occurred mostly through reflection and action and was often linked to the learning of others. Most important to enhance informal learning from these learning opportunities was the realisation of a climate of collaboration and trust. Possible new directions for future research on informal learning from error in hospitals might focus on ways to measure informal learning and the balance between formal and informal learning. Finally, 12 recommendations about how hospitals could enhance informal learning within their organisation are given.

A comprehensive overview of medical error in hospitals using incident-reporting systems, patient complaints and chart review of inpatient deaths.

BACKGROUND: Incident reporting systems (IRS) are used to identify medical errors in order to learn from mistakes and improve patient safety in hospitals. However, IRS contain only a small fraction of occurring incidents. A more comprehensive overview of medical error in hospitals may be obtained by combining information from multiple sources. The WHO has developed the International Classification for Patient Safety (ICPS) in order to enable comparison of incident reports from different sources and institutions. METHODS: The aim of this paper was to provide a more comprehensive overview of medical error in hospitals using a combination of different information sources. Incident reports collected from IRS, patient complaints and retrospective chart review in an academic acute care hospital were classified using the ICPS. The main outcome measures were distribution of incidents over the thirteen categories of the ICPS classifier "Incident type", described as odds ratios (OR) and proportional similarity indices (PSI). RESULTS: A total of 1012 incidents resulted in 1282 classified items. Large differences between data from IRS and patient complaints (PSI = 0.32) and from IRS and retrospective chart review (PSI = 0.31) were mainly attributable to behaviour (OR = 6.08), clinical administration (OR = 5.14), clinical process (OR = 6.73) and resources (OR = 2.06). CONCLUSIONS: IRS do not capture all incidents in hospitals and should be combined with complementary information about diagnostic error and delayed treatment from patient complaints and retrospective chart review. Since incidents that are not recorded in IRS do not lead to remedial and preventive action in response to IRS reports, healthcare centres that have access to different incident detection methods should harness information from all sources to improve patient safety.

Gene-load score of the renin-angiotensin-aldosterone system is associated with coronary heart disease in familial hypercholesterolaemia.

AIMS: Familial hypercholesterolaemia (FH) is characterized by premature coronary heart disease (CHD). However, the incidence of CHD varies considerably among FH patients. Genetic variation in the renin-angiotensin-aldosterone system (RAAS) and the adrenalin/noradrenalin system may be of importance in determining the CHD risk in FH, because of their involvement in CHD. We investigated the association between CHD risk and combined genetic variation in the RAAS and adrenalin/noradrenalin system. METHODS AND RESULTS: In 2190 FH patients, we genotyped six RAAS polymorphisms and five adrenalin/noradrenalin polymorphisms. For each patient, we calculated two gene-load scores by counting the number of risk genotypes within each pathway. Four of the six RAAS polymorphisms and none of the polymorphisms in the adrenalin/noradrenalin system were significantly associated with CHD (P < 0.05). The RAAS gene-load score was significantly associated with CHD (P(linear trend) < 0.001): in patients with a gene-load score of 5 or 6, the CHD risk was 2.3 times as high as in patients with a score of 0 or 1. The gene-load score of the adrenalin/noradrenalin system was not associated with CHD. CONCLUSION: Genetic variation in the RAAS contributes gene-dose dependently to CHD risk in patients with FH, whereas genetic variation in the adrenalin/noradrenalin system is not associated with CHD.

The M235T polymorphism in the angiotensinogen gene is associated with the risk of malignant hypertension in white patients.

BACKGROUND: Malignant hypertension can be considered an extreme phenotype of renin-mediated hypertension. Therefore, we compared the allelic frequencies of the angiotensinogen (AGT) M235T, angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II-type I receptor (AT1R) A1166C polymorphisms in malignant hypertensive patients with hypertensive and normotensive controls. METHODS: A total of 101 consecutive patients between 1995 and 2005 admitted to a large university hospital fulfilled the criteria for malignant hypertension. Seventy-five patients (74%) were compared with 150 hypertensive and 150 normotensive controls, randomly selected from a population study and individually matched on age, sex and ethnicity. RESULTS: The odds of malignant hypertension in white subjects with the TT genotype of the AGT M235T polymorphism was 14.3 (5.5-37) compared to hypertensive controls, and 9.4 (3.8-23.2) compared to normotensive controls. Adjustment for age, sex, smoking and antihypertensive therapy did not affect this association. The association of AGT M235T with malignant hypertension was not significant in blacks. In patients with malignant hypertension, the TT genotype was associated with more severe renal dysfunction and microangiopathic haemolysis. No differences were found in allele frequencies of the ACE I/D or the AT1R A1166C polymorphisms between study groups. CONCLUSIONS: The TT genotype of AGT M235T is associated with malignant hypertension in whites, carriers having an odds of approximately 10 to 1 compared to hypertensive and normotensive controls. These observations may provide a better understanding of the pathophysiology of malignant hypertension and offer possibilities for identifying patients at risk. Larger association or linkage studies are needed for a more detailed risk assessment.

The renin-angiotensin system in malignant hypertension revisited: plasma renin activity, microangiopathic hemolysis, and renal failure in malignant hypertension.

BACKGROUND: Malignant hypertension is a renin-dependent form of hypertension. However, the variations in renin-angiotensin system (RAS) activation in malignant hypertension are not completely understood. A proposed mechanism for ongoing RAS activation is the presence of microangiopathic hemolysis resulting in renovascular ischemia. METHODS: We prospectively examined the association between plasma renin activity (PRA), microangiopathic hemolysis, and renal dysfunction in 30 consecutive patients with malignant hypertension (n=18) and severe hypertension (n=12). The PRA and aldosterone were measured in the supine position and before initiating therapy. RESULTS: The PRA was 8.8 ng angiotensin I (AI)/mL/h (interquartile range [IQR] 4.8-20) in malignant hypertensive patients and 2.8 ng AI/mL/h (IQR 0.6-6.3) in patients with severe hypertension (P<.01). Aldosterone was 1.30+/-1.02 nmol/L in patients with malignant hypertension compared with 0.44+/-0.37 nmol/L in those with severe hypertension (P<.01). In malignant hypertension, PRA highly correlated with lactic dehydrogenase (LDH) (r=0.76, P<.001), meaning that 58% of the variations in PRA could be explained by LDH. The PRA positively correlated with serum creatinine values at presentation (r=0.50, P=.007), but adjustment for LDH abolished the effect of PRA on creatinine (P=.24). CONCLUSIONS: The PRA and aldosterone were markedly elevated in patients with malignant hypertension but not in severely hypertensive patients despite small differences in blood pressure (BP). The strong logarithmic correlation between PRA, microangiopathic markers, and renal dysfunction suggests a renin-mediated acceleration of vascular damage and renal dysfunction in patients with malignant hypertension.

Creatine kinase activity is associated with blood pressure.

BACKGROUND: We previously hypothesized that high activity of creatine kinase, the central regulatory enzyme of energy metabolism, facilitates the development of high blood pressure. Creatine kinase rapidly provides adenosine triphosphate to highly energy-demanding processes, including cardiovascular contraction, and antagonizes nitric oxide-mediated functions. Relatively high activity of the enzyme, particularly in resistance arteries, is thought to enhance pressor responses and increase blood pressure. Tissue creatine kinase activity is reported to be high in black people, a population subgroup with greater hypertension risk; the proposed effects of high creatine kinase activity, however, are not "race dependent." We therefore assessed whether creatine kinase is associated with blood pressure in a multiethnic population. METHODS AND RESULTS: We analyzed a stratified random sample of the population of Amsterdam, The Netherlands, consisting of 1444 citizens (503 white European, 292 South Asian, 580 black, and 69 of other ethnicity) aged 34 to 60 years. We used linear regression analysis to investigate the association between blood pressure and normal serum creatine kinase after rest, as a substitute measure of tissue activity. Creatine kinase was independently associated with blood pressure, with an increase in systolic and diastolic pressure, respectively, of 8.0 (95% CI, 3.3 to 12.7) and 4.7 (95% CI, 1.9 to 7.5) mm Hg per log creatine kinase increase after adjustment for age, sex, body mass index, and ethnicity. CONCLUSIONS: Creatine kinase is associated with blood pressure. Further studies are needed to explore the nature of this association, including how variation in cardiovascular creatine kinase activity may affect pressor responses.

Ethnic disparities in the incidence, presentation and complications of malignant hypertension.

BACKGROUND: The incidence of malignant hypertension has declined after the introduction of antihypertensive agents. However, previous reports have suggested that malignant hypertension may be relatively common in multi-ethnic populations. The aim of this study was to compare ethnic disparities in the incidence, clinical characteristics and complications of malignant hypertension. METHODS: A retrospective cohort study on malignant hypertension in a multi-ethnic population in Amsterdam, the Netherlands, between August 1993 and August 2005. RESULTS: A total of 122 patients with malignant hypertension were included, mean age 44 years (+/- 12), 66% were men and 47% were black. The incidence rate remained approximately 2.6 (+/- 0.9) per 100,000 per year and was higher among blacks. Black individuals had higher systolic blood pressure (234 +/- 23 versus 225 +/- 22, P = 0.03) and more renal dysfunction compared with white individuals (39% with serum creatinine > 300 micromol/l versus 22%, P = 0.04). Hypertension was previously diagnosed in 58% of all patients, 37% received medication, and 23% stopped their drugs before admission. Health insurance was absent in 25% of black and 2% of white patients (P < 0.01). Secondary causes were identified in 40% of white and 10% of black subjects (P < 0.01). After a mean follow-up of 4.0 +/- 3.2 years 10% had died and 19% needed renal replacement therapy. Renal failure was more frequent in black than in white individuals (hazard ratio 2.8; 95% confidence interval 1.1-7.2), but mainly because of higher serum creatinine levels at presentation. CONCLUSION: The incidence of malignant hypertension and related renal complications is higher in black compared with white individuals. These differences may be explained by ethnic disparities in blood pressure control, drug adherence and insurance status.

Microangiopathic hemolysis and renal failure in malignant hypertension.

Renal dysfunction is an important cause of morbidity and mortality in patients with malignant hypertension. Microangiopathic hemolysis (MAHA) related to malignant hypertension may cause renal insufficiency by obstruction of interlobular arteries. We hypothesized that the presence of MAHA is an important indicator of renal dysfunction and recovery in malignant hypertension. We retrospectively analyzed 97 patients admitted between April 1994 and April 2004 with malignant hypertension. MAHA was defined as a low platelet count (<150x10(9)/L) with either an elevated lactic dehydrogenase (>220 U/L) or presence of schistocytes. MAHA was present in 26 of 97 patients (27%). Serum creatinine levels at admission were significantly higher in those with than in those without MAHA: median serum creatinine 690 micromol/L (interquartile range [IQR] 394 to 1105) and 120 micromol/L (IQR 82 to 211), respectively (P<0.01). Macroalbuminuria was present in 88% with versus 41% without MAHA (P<0.01). Patients with MAHA were more often black (73%; P<0.01) and had higher systolic blood pressure (mean 242 mm Hg versus 225 mm Hg; P<0.01). Dialysis was needed in 15 patients with MAHA (58%) versus 2 patients (3%) without MAHA. In 6 patients with MAHA, dialysis could be stopped. Cox regression analysis showed that MAHA and systolic blood pressure were the most important indicators of renal improvement during follow-up, with a hazard ratio of 0.24 (95% confidence interval [CI], 0.08 to 0.75; P=0.01) and 1.02 per mm Hg increase in systolic blood pressure (95% CI, 1.01 to 1.05; P=0.01). In conclusion, MAHA is an important indicator of renal insufficiency and recovery in patients with malignant hypertension.

Impaired cerebral autoregulation in patients with malignant hypertension.

BACKGROUND: In patients with a malignant hypertension, immediate parenteral treatment with blood pressure-lowering agents such as intravenous sodium nitroprusside (SNP) is indicated. In this study, we evaluated static and dynamic cerebral autoregulation (CA) during acute blood pressure lowering with SNP in these patients. METHODS AND RESULTS: In 8 patients with mean arterial pressure (MAP) >140 mm Hg and grade III or IV hypertensive retinopathy at hospital admission, middle cerebral artery blood velocity (MCA V) and blood pressure were monitored. Dynamic CA was expressed as the 0.1-Hz MCA V(mean) to MAP phase lead and static CA as the MCA V(mean) to MAP relationship during SNP treatment. Eight normotensive subjects served as a reference group. In the patients, the MCA V(mean) to MAP phase lead was lower (30+/-8 degrees versus 58+/-5 degrees , mean+/-SEM; P<0.05), whereas the transfer gain tended to be higher. During SNP treatment, target MAP was reached within 90 minutes in all patients. The MCA V(mean) decrease was 22+/-4%, along with a 27+/-3% reduction in MAP (from 166+/-4 to 121+/-6 mm Hg; P<0.05) in a linear fashion (averaged slope, 0.82+/-0.15% cm x s(-1) . % mm Hg(-1); r=0.70+/-0.07). CONCLUSIONS: In patients with malignant hypertension, dynamic CA is impaired. An MCA V(mean) plateau was not detected during the whole SNP treatment, indicating loss of static CA as well. This study showed that during the whole rapid reduction in blood pressure with SNP, MCA V(mean) decreases almost one on one with MAP.