Effect of captopril on renal extraction of renin, angiotensin II, atrial natriuretic peptide and vasopressin, and renal vein renin ratio in patients with arterial hypertension and unilateral renal artery disease

Plasma renin activity (PRA) and plasma concentrations of angiotensinII (AngII), atrial natriuretic peptide (ANP) and arginine vasopressin(AVP) were determined in the abdominal aorta and the renal veinsbefore and 1 h after peroral ingestion of captopril 25 mg in29 patients with arterial hypertension and unilateral renalartery stenosis or occlusion, in order to study the effect ofACE inhibition on single-kidney extraction ratio (ER) of PRA,AngII, ANP, and AVP, and on renal vein renin ratio (RVRR). PRAwas increased, AngII and ANP were reduced, and AVP unchangedafter captopril. On the affected side the negative ER of PRA(–1.03) and AngII (–0.28) and the positive ER ofANP (0.25) and AVP (0.14) were not significantly changed bycaptopril. On the non-affected side ER of AngII and ER of ANPwere significantly reduced (ER of AngII, 0.41–0.00, ERof ANP, 0.29–0.17), but ER of PRA and ER of AVP were unchanged.RVRR was not significantly changed by captopril. RVRR was greaterthan 1.5 in 79% of the patients before captopril, in 82% aftercaptopril, and in 93% either before or after captopril. It is concluded that captopril reduces ER of AngII and ER ofANP on the non-affected side but not on the affected side inunilateral renal artery disease with hypertension, and thatthe use of RVRR both before and after captopril improves thepredictive value of RVRR with regard to the diagnosis of unilateralrenal artery disease.     

Hemodynamic effects of vasopressin antagonism and angiotensin I converting enzyme inhibition during halothane anesthesia in sheep

The hemodynamic effects of separate and combined intravenous administration of the vasopressin (AVP) V1-receptor antagonist SK&F 100273 (10 micrograms/kg) and the angiotensin I converting enzyme inhibitor captopril (20 mg + 1 mg/h) were studied in 12 sheep during stable halothane anesthesia (1.5% end-tidal conc.). The separate blockade of either V1-receptors or angiotensin II (ANG II) synthesis induced a small (7-10%), but significant, fall in mean systemic arterial pressure (MSAP), whereas the combined treatment caused a 30% reduction in blood pressure. The changes in systemic vascular resistance paralleled those of the MSAP. Consequently, the cardiac output was largely unaffected by the interference with AVP effects and/or ANG II synthesis. The halothane anesthesia effectively increased the plasma levels of AVP and ANG II, and plasma renin activity without any relation to changes in MSAP. When either the AVP effects or ANG II synthesis were blocked separately, there was a slight tendency for a compensatory increase of the unimpeded hormonal system. It is concluded that halothane anesthesia increases the plasma levels of AVP and ANG II in sheep, and that the maintenance of the arterial pressure is dependent on the concurrent vasopressor effects of the two hormones in this situation.     

Comparison of the role of endothelin, vasopressin and angiotensin in arterial pressure regulation during sevoflurane anaesthesia in dogs

Background. In this study we aimed to clarify the role of endothelinin arterial pressure regulation during anaesthesia with increasingconcentrations of sevoflurane (1–3 MAC) and compare itwith those of vasopressin and angiotensin. Methods. After an awake control period, on different days, sixdogs underwent each of the following four interventions: sevofluraneanaesthesia alone (1–3 MAC), sevoflurane after block ofeither endothelin receptors using tezosentan (3 mg kg^–1followed by 3 mg kg^–1 h^–1), vasopressinV_1a receptors using [d(CH₂)₅Tyr(Me²)]AVP (40 µg kg^--1)or angiotensin receptors using losartan (6 mg kg^–1 h^–1).Plasma concentrations of endothelin, big endothelin, vasopressinand renin were measured. Effects of sevoflurane in the presenceand absence of the respective receptor block were analysed andcompared using analysis of variance for repeated measures (ANOVAfollowed by Fisher’s PLSD (protected least significantdifference) (P<0.05)). Results. Mean arterial pressure decreased in a dose-dependentmanner with sevoflurane during all interventions. At 1 MAC,this decrease was greatest during angiotensin receptor block(mean (SEM), –41 (3) mm Hg), intermediate duringvasopressin and endothelin receptor block (–31 (4) and–30 (2) mm Hg respectively), and least during sevofluranealone (–24 (3) mm Hg). The course of systemic vascularresistance mirrored the course of arterial pressure, while cardiacoutput did not differ between groups. Plasma concentrationsof endothelin, big endothelin and renin did not change duringany intervention, whereas vasopressin concentration increasedfrom     

Plasma erythropoietin concentrations in renal venous blood of patients with unilateral renovascular hypertension.

In 19 patients with unilateral renal artery stenosis and subsequent renovascular hypertension plasma renin activity (PRA), plasma concentrations of atrial natriuretic peptide (ANP), erythropoietin (Epo), H+ and HCO3-, as well as pO2 and pCO2 were assessed in renal venous blood of the 'ischaemic' and normally perfused kidney, both in arterial blood and in the inferior vena cava distally from the orifices of the renal veins. PRA and ANP were significantly elevated in venous blood of the ischaemic kidney as compared with the normally perfused kidney. In contrast to PRA and ANP, plasma concentrations of Epo were similar in blood withdrawn at all vascular sites. pO2 and pCO2, as well as blood H+ and HCO3- concentrations in venous blood of the ischaemic kidney were of the same magnitude as of the normally perfused kidney. From the results presented in this paper it follows that (i) in contrast to plasma renin activity and ANP, unilateral renal 'ischaemia' does not influence plasma concentrations of Epo in renal venous blood, and (ii) chronic haemodynamic alterations do not seem to influence Epo secretion by the kidneys.     

Renal effects of human atrial natriuretic peptide in patients after major vascular surgery

The effects were studied postoperatively of an infusion of atrial natriuretic peptide (ANP) 7.5 pMol–kg^-1 –min^-1 on renal function and haemodynamics in seven patients who had been operated with insertion of an abdominal aortic graft. Urine flow, glomerular filtration rate (GFR), renal plasma flow (RPF) and excretion of electrolytes and osmoles were measured for three periods of 20 minutes during infusion of ANP, in the morning of the day after surgery. Haemodynamic studies were conducted, and serum levels of ANP, catecholamines and plasma renin activity were measured.
ANP levels increased from 52 to approximately 250 pMol–L^-1 during ANP infusion and decreased after infusion to a level equal to baseline. GFR increased from 92 mL–min"¹ by 58, 20 and 21%, respectively. RPF was unchanged. Urine flow rate increased from 1.99 mL–min"' by 81, 151 and 173%, respectively. Fractional clearances of sodium, chloride and osmoles were increased during the second and third ANP periods whereas fractional potassium clearance did not change during the study. There were no changes in catecholamine levels or plasma renin activity during the study. Heart rate, mean arterial pressure and calculated systemic and pulmonary vascular resistance did not change whereas reductions occurred in cardiac index, mean pulmonary artery pressure, pulmonary artery wedge pressure and mean right atrial pressure. We conclude that infusion of ANP also in the postoperative situation increases GFR, diuresis and sodium excretion.     

Haemodynamic effects of famotidine and cimetidine in critically ill patients

To compare the cardiovascular effects of the histamine H2 receptor antagonists, famotidine and cimetidine, in critically ill patients, seven ICU patients were given 20 mg of famotidine or 200 mg of cimetidine intravenously in a randomized fashion. Each patient was studied on 2 separate days. In a random fashion, they received famotidine on one of the days and cimetidine on the other. Mean systemic arterial pressure (MAP) was maximally decreased 2 min after intravenous cimetidine from 103 +/- 10 (13.7 +/- 1.3 kPa) (mean +/- s.d.) to 83 +/- 15 mmHg (11.1 +/- 2.0 kPa) (P less than 0.05). MAP returned to control values 8 min after administration of the drug. Systemic vascular resistance (SVR) was significantly decreased during the 8-min observation period (P less than 0.01). In contrast, famotidine produced little haemodynamic effect over the 8-min period. Therefore, we suggest that famotidine may be a better H2 antagonist than cimetidine in critically ill patients requiring vasoconstrictor drug support, since it avoids the significant decrease in systemic blood pressure and peripheral vasodilation seen after cimetidine.     

Hemodynamic effects of dopamine in critically ill septic patients.

The hemodynamic effects of various doses of dopamine were studied in 20 severely septic hypotensive patients, 18 of whom also had moderate or severe acute respiratory failure. Dopamine raised the mean arterial blood pressure in virtually all instances by an average of 21 mm Hg (+28%). This increase in blood pressure was brought about primarily by an increase in cardiac index (average +19%) with only a minimal average increase (3%) in the systemic vascular resistance index. There was little or no change in pulse rate, central venous pressure, pulmonary artery pressure, or pulmonary wedge pressure. Left heart function, as reflected by stroke work index increased significantly (+55%), but right ventricular stroke work index increased by only 17%, and the pulmonary vascular resistance index fell by an average of 3%.Dopamine appears to be a very useful agent for improving systemic blood pressure in hypotension complicating sepsis with little or no adverse effects on the lungs or pulmonary hemodynamics.     

The immunomodulatory effects of prolonged intravenous infusion of propofol versus midazolam in critically ill surgical patients

Both propofol and midazolam are known to inhibit immune function. The aim of this study was to investigate cytokine production in critically ill surgical patients as early markers of immune response to prolonged infusion of propofol and midazolam. The study enrolled 40 elective patients who were to receive long-term sedation for more than 2 days. Patients were randomly allocated to one of two equally sized groups. Central venous blood samples for measurement of interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were drawn prior to the start and after 48 h of infusion. After 48 h, propofol caused significant increases in IL-1beta (24%), IL-6 (23%) and TNF-alpha (4.8 times) levels, while midazolam caused significant decreases in IL-1beta (21%), IL-6 (21%) and TNF-alpha (19%). Both agents caused significant decreases in IL-8 levels (propofol: 30%, midazolam: 48%, p < 0.05). Propofol caused significant decreases in IL-2 levels (68%, p < 0.001) but increases in IFN-gamma (30%, p < 0.05), whereas there was no significant change with midazolam compared with the pre-infusion level. In conclusion, during 48 h of continuous infusion, propofol stimulated, while midazolam suppressed, the production of the pro-inflammatory cytokines IL-1beta, IL-6 and TNF-alpha, and both caused suppression of IL-8 production. Propofol inhibited IL-2 production and stimulated IFN-gamma production, whereas midazolam failed to do so. Therefore, sedative agents may have clinical implications in high-risk and immunocompromised patients.     

Beneficial effects of intensive insulin therapy in critically ill patients.

Critically ill patients in intensive care units (ICU) for morethan a few days have a mortality of approximately 20% world-wide.These critically ill patients, in the absence of a previousdiagnosis of diabetes, commonly exhibit stress hyperglycemiaand insulin resistance [1]. Many of these critically ill patientsdie of multiorgan dysfunction (MOD) and sepsis. Since stresshyperglycemia has been shown to associate with impaired polymorphonuclearneutrophil function and bactericidal activity [2], the questionarose whether lowering of blood glucose in critically ill patientswould decrease morbidity and mortality. To address this question the Leuven group of Van den Bergheand associates performed a prospective, randomized control studyin 1548 patients admitted to their surgical ICU who were receivingmechanical ventilation [3]. The patients were randomly assignedto receive intensive     

Neurohormonal factors in the pathogenesis of essential hypertension

Summary: The level of arterial pressure in an individual is dictated by many interacting factors including neurohormonal systems. Heightened activity of pressor systems could contribute to the pathogenesis of essential hypertension; evidence for this is strongest for sympathetic overactivity in some young patients. Inadequacy of vasodilator systems, especially natriuretic peptides or nitric oxide, has also been suggested as central to the pathogenesis of essential hypertension although evidence is far from definitive. the existence of authentic ouabain in human plasma, let alone its pathophysiological importance in hypertension, is now in doubt. Information is awaited regarding the role of the endothelins and adrenomedullin in physiology and in essential hypertension.     

Effects of dexmedetomidine on adrenocortical function, and the cardiovascular, endocrine and inflammatory responses in post-operative patients needing sedation in the intensive care unit

We have compared the effects of dexmedetomidine and propofolon endocrine, metabolic, inflammatory and cardiovascular responsesin patients in the intensive care unit (ICU) after major surgery.Twenty patients who were expected to require 8 h of post-operativesedation and ventilation were allocated randomly to receiveeither an infusion of dexmedetomidine 0.2–2.5 µg kg^–1 h^–1or propofol 1–3 mg kg^–1 h^–1.Arterial pressure, heart rate and sequential concentrationsof circulating cortisol, adrenocorticotrophic hormone (ACTH),growth hormone, prolactin, insulin, glucose and interleukin 6were measured. An ACTH stimulation test was performed in allpatients who received dexmedetomidine. Heart rate was significantlylower in the dexmedetomidine patients. There were no differencesin arterial pressure, cortisol, ACTH, prolactin and glucoseconcentrations between the two groups. A positive response tothe ACTH stimulation test varied depending on the diagnosticcriteria used. The insulin concentration was significantly lowerin the dexmedetomidine group at 2 h (P=0.021), althoughthis did not affect blood glucose concentrations. Growth hormoneconcentrations were significantly higher in dexmedetomidine-treatedpatients overall (P=0.036), but circulating concentrations remainedin the physiological range. Interleukin 6 decreased inthe dexmedetomidine group. We conclude that dexmedetomidineinfusion does not inhibit adrenal steroidogenesis when usedfor short-term sedation after surgery. Br J Anaesth 2001: 86: 650–6     

危重症患者内镜引导下可视化鼻肠管置管方法及效果

目的 探索内镜引导下可视化鼻肠管置管在危重症患者中的应用效果。方法 将100例危重症患者按鼻肠管置管时间分为对照组和观察组各50例。对照组采用床旁盲插置入鼻肠管,观察组采用内镜引导下可视化置入鼻肠管。结果 观察组首次置管成功率显著高于对照组,置管耗时显著短于对照组,置管过程中患者平均动脉压、心率、血氧饱和度波动显著小于对照组(均P<0.05),观察组患者大便潜血、鼻腔黏膜出血及渗血、误入气道发生率显著低于对照组(均P<0.05)。结论 内镜引导下可视化鼻肠管置管可提高患者首次置管成功率,缩短置管时间,减少置管过程中患者血压、心率和血氧饱和度变化,降低置管并发症发生率。     

The effects of propofol and dexmedetomidine infusion on fluid responsiveness in critically ill patients

Background

We studied the effects of propofol or dexmedetomidine on preload dependency and fluid responsiveness in critically ill patients.

Methods

In the study, we included 91 patients with acute circulatory failure (70 ± 15 y) who received propofol (n = 45 patients, PROP group) or dexmedetomidine (n = 46 patients, DEX group). An initial passive leg-raising (PLR 1) test was performed in all patients to evaluate preload dependency at baseline. Propofol and dexmedetomidine were infused and titrated according to the Richmond Agitation Sedation Scale; the results ranged from −2 to −1, and the bispectral index values ranged from 60–75. A second PLR test (PLR 2) was performed before administration of a 250-mL normal saline fluid challenge over a 5-min period. We obtained central venous pressure and cardiac index (CI) measurements before and after the two PLR tests and volume expansion. An increase of ≥10% in CI during PLR was considered to be a positive test finding that was indicative of preload dependency, whereas an increase of <10% in CI during PLR was considered to be a negative test finding.

Results

At baseline, 22 of 45 patients had negative PLR 1 in the PROP group, whereas 20 of 46 patients had negative PLR 1 in the DEX group. After propofol or dexmedetomidine sedation, there were significant decreases in CI (−9.5% [±6.6%] versus −16.4% [±8.5%], P < 0.001) in the PROP and DEX groups, respectively. In the PROP group, there were significant increases in CI (+18.4% [±9.5%] versus +10.7% [±12.3%], P < 0.05) induced by PLR 2 compared with that induced by PLR 1. In the DEX group, there were no significant increases in CI (+13.2% [±14.9%] versus +12.8% [±17.7%]) induced by PLR 2 compared with that induced by PLR 1. Although the mean arterial pressure values increased comparably with the volume expansion observed in both groups, the volume expansion resulted in a significantly higher increase in CI compared with the baseline values in the PROP group (3.2 ± 0.8 versus 3.2 ± 0.7 L/min/m²) but not in the DEX group (2.9 ± 0.7 versus 3.1 ± 0.8 L/min/m², P < 0.05).

Conclusions

We observed that propofol infusion, but not dexmedetomidine infusion, can increase preload dependency and fluid responsiveness in patients with circulatory failure.     

Hemodynamic effects of a continuous infusion of levosimendan in critically ill patients with cardiogenic shock requiring catecholamines

BACKGROUND: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in desperately ill patients with cardiogenic shock requiring catecholamines. METHODS: Ten patients with cardiogenic shock received levosimendan as continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. The patients were otherwise unselected. Hemodynamic measurements were routinely performed at baseline (time 0) and at 1, 8, 16 and 24 h after start of levosimendan (LS) using a Swan-Ganz thermodilution catheter. RESULTS: During the levosimendan infusion there was a significant increase in cardiac index from 1.8 +/- 0.4 to 2.4 +/- 0.6 L*min-1*m-2 (P = 0.023) and a significant decrease in systemic vascular resistance from 1559 +/- 430 to 1109 +/- 202 dyn*s*cm-5 (P = 0.001), respectively. Changes in catecholamine dose, and in systolic and diastolic blood pressure were not significant. Given the individual response to LS, 8/10 patients showed an increase in left ventricular stroke work index under reduced or roughly unchanged preload conditions after 8 h. CONCLUSION: This series shows that a LS infusion is feasible and able to improve hemodynamics in severely compromized, critically ill patients with cardiogenic shock requiring catecholamine therapy. Its potential advantages when compared with other inotropes are unclear. To clarify the potential role of LS in this clinical setting randomized controlled trials on hemodynamic and mortality endpoints are needed.     

Haemodynamic and renal effects of intravenous enalaprilat during coronary artery bypass graft surgery in patients with ischaemic heart dysfunction

Renal dysfunction occurring after open heart surgery is multifactorialin origin but activation of the renin–angiotensin systemmay have a prominent role. Fourteen patients with ischaemicheart dysfunction scheduled for elective coronary artery bypassgraft (CABG) surgery were allocated to a treatment group [enalaprilatfor 2 days; ACEI (angiotensin-converting enzyme inhibitor) group,n=7] or a control group (n=7). The cardiac index was significantlyhigher in ACEI-treated patients than in the controls beforeand after cardiopulmonary bypass (CPB) (P<0.05) and on postoperativeday 2 (P<0.05). The systemic vascular resistance wassignificantly lower in the ACEI-treated patients than in thecontrols before and after CPB (P<0.05). Renal plasma flow,measured as [¹³¹I]orthoiodohippuran clearance (Cl_H), was higherin the ACEI group than in the control group before CPB, as wasendogenous creatinine clearance after CPB (P<0.05). On post-operativeday 7, Cl_H was significantly higher in the ACEI group thanin the control group (P<0.05). Plasma renin activity andvasopressin concentration increased in both groups during CPB(P<0.05). The study demonstrates that administration of ani.v. ACEI, enalaprilat, improves cardiac output during CABGsurgery in patients with ischaemic heart dysfunction. Moreover,renal perfusion was better maintained during surgery, and thiseffect was sustained up to post-operative day 7. Br J Anaesth 2001; 86: 169–75     

Haemodynamic effects of parenteral vs. enteral paracetamol in critically ill patients: a randomised controlled trial

Paracetamol is a commonly used drug in the intensive care unit. There have been reports in the literature of an association with significant hypotension, a potentially important interaction for labile critically ill patients. Route of administration may influence the incidence of hypotension. This single‐centre, prospective, open‐label, randomised, parallel‐arm, active‐control trial was designed to determine the incidence of hypotension following the administration of paracetamol to critically ill patients. Fifty adult patients receiving paracetamol for analgesia or pyrexia were randomly assigned to receive either the parenteral or enteral formulation of the drug. Paracetamol concentrations were measured at baseline and at multiple time points over 24 h. The maximal plasma paracetamol concentration was significantly different between routes; 156 vs. 73 micromol.l^?1 [p = 0.0005] following the first dose of parenteral or enteral paracetamol, respectively. Sixteen hypotensive events occurred in 12 patients: parenteral n = 12; enteral n = 4. The incident rate ratio for parenteral vs. enteral paracetamol was 2.94 (95% CI 0.97–8.92; p = 0.06). The incidence of hypotension associated with paracetamol administration is higher than previously reported and tends to be more frequent with parenteral paracetamol.