OBJECTIVE: To investigate the correlation between early-stage blood pressure indexes and prognosis in sepsis patients. METHODS: A retrospective cohort study was conducted on the medical records of patients diagnosed with sepsis from 2001 to 2012 in the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients were divided into survival group and death group according to the 28-day prognosis. General data of patients and heart rate (HR) and blood pressure at admission to ICU and within 24 hours after admission were collected. The blood pressure indexes including the maximum, median and mean value of systolic index, diastolic index and mean arterial pressure (MAP) index were calculated. The data were randomly divided into training set and validation set (4 : 1). Univariate Logistic regression analysis was used to screen covariates, and multivariate Logistic stepwise regression models were further developed. Model 1 (including HR, blood pressure, and blood pressure index related variables with P < 0.1 and other variables with P < 0.05) and Model 2 (including HR, blood pressure, and blood pressure index related variables with P < 0.1) were developed respectively. The receiver operator characteristic curve (ROC curve), precision recall curve (PRC) and decision curve analysis (DCA) curve were used to evaluate the quality of the two models, and the influencing factors of the prognosis of sepsis patients were analyzed. Finally, nomogram model was developed according to the better model and effectiveness of it was evaluated. RESULTS: A total of 11 559 sepsis patients were included in the study, with 10 012 patients in the survival group and 1 547 patients in the death group. There were significant differences in age, survival time, Elixhauser comorbidity score and other 46 variables between the two groups (all P < 0.05). Thirty-seven variables were preliminarily screened by univariate Logistic regression analysis. After multivariate Logistic stepwise regression model screening, among the indicators related to HR, blood pressure and blood pressure index, the HR at admission to ICU [odds ratio (OR) = 0.992, 95% confidence interval (95%CI) was 0.988-0.997] and the maximum HR (OR = 1.006, 95%CI was 1.001-1.011), maximum MAP index (OR = 1.620, 95%CI was 1.244-2.126), mean diastolic index (OR = 0.283, 95%CI was 0.091-0.856), median systolic index (OR = 2.149, 95%CI was 0.805-4.461), median diastolic index (OR = 3.986, 95%CI was 1.376-11.758) were selected (all P < 0.1). There were 14 other variables with P < 0.05, including age, Elixhauser comorbidity score, continuous renal replacement therapy (CRRT), use of ventilator, sedation and analgesia, norepinephrine, norepinephrine, highest serum creatinine (SCr), maximum blood urea nitrogen (BUN), highest prothrombin time (PT), highest activated partial thromboplastin time (APTT), lowest platelet count (PLT), highest white blood cell count (WBC), minimum hemoglobin (Hb). The ROC curve showed that the area under the curve (AUC) of Model 1 and Model 2 were 0.769 and 0.637, respectively, indicating that model 1 had higher prediction accuracy. The PRC curve showed that the AUC of Model 1 and Model 2 were 0.381 and 0.240, respectively, indicating that Model 1 had a better effect. The DCA curve showed that when the threshold was 0-0.8 (the probability of death was 0-80%), the net benefit rate of Model 1 was higher than that of Model 2. The calibration curve showed that the prediction effect of the nomogram model developed according to Model 1 was in good agreement with the actual outcome. The Bootstrap verification results showed that the nomogram model was consistent with the above results and had good prediction effects. CONCLUSIONS The nomogram model constructed has good prediction effects on the 28-day prognosis in sepsis patients, and the blood pressure indexes are important predictors in the model.
Humans ; Cohort Studies ; Retrospective Studies ; Blood Pressure ; Intensive Care Units ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; Critical Care ; Norepinephrine

BACKGROUND: Vasoplegic syndrome is an increasingly recognized disease in perioperative medicine and is characterized by severe hypotension, normal or elevated cardiac output, and decreased systemic vascular resistance. It occurs commonly after cardiopulmonary bypass but may also occur after other types of surgery.CASE: Vasoplegic syndrome developed in our patient during posterior lumbar interbody fusion because of administering nicardipine after phenylephrine. However, the blood pressure did not increase as expected despite simultaneous use of norepinephrine and vasopressin to increase the reduced systemic vascular resistance.CONCLUSIONS: We present a case of vasoplegic syndrome that developed during posterior lumbar interbody fusion and was treated successfully with methylene blue.
Blood Pressure ; Cardiac Output ; Cardiopulmonary Bypass ; Humans ; Hypotension ; Methylene Blue ; Nicardipine ; Norepinephrine ; Phenylephrine ; Vascular Resistance ; Vasoplegia ; Vasopressins

Chronic kidney disease (CKD) is increasing worldwide without an effective therapeutic strategy. Sympathetic nerve activation is implicated in CKD progression, as well as cardiovascular dysfunction. Renal denervation is beneficial for controlling blood pressure (BP) and improving renal function through reduction of sympathetic nerve activity in patients with resistant hypertension and CKD. Sympathetic neurotransmitter norepinephrine (NE) via adrenergic receptor (AR) signaling has been implicated in tissue homeostasis and various disease progressions, including CKD. Increased plasma NE level is a predictor of survival and the incidence of cardiovascular events in patients with end-stage renal disease, as well as future renal injury in subjects with normal BP and renal function. Our recent data demonstrate that NE derived from renal nerves causes renal inflammation and fibrosis progression through alpha-2 adrenergic receptors (α₂-AR) in renal fibrosis models independent of BP. Sympathetic nerve activation-associated molecular mechanisms and signals seem to be critical for the development and progression of CKD, but the exact role of sympathetic nerve activation in CKD progression remains undefined. This review explores the current knowledge of NE-α₂-AR signaling in renal diseases and offers prospective views on developing therapeutic strategies targeting NE-AR signaling in CKD progression.
Blood Pressure ; Denervation ; Disease Progression ; Fibrosis ; Homeostasis ; Humans ; Hypertension ; Incidence ; Inflammation ; Kidney Failure, Chronic ; Neurotransmitter Agents ; Norepinephrine ; Plasma ; Prospective Studies ; Receptors, Adrenergic ; Receptors, Adrenergic, alpha-2 ; Renal Insufficiency, Chronic ; Reperfusion Injury

Antihypertensive effects of ethanol extracts of Aralia elata (Miq.) Seem. (AE) were investigated in spontaneously hypertensive rats (SHR). SHR aged 14 weeks were treated for 8 weeks with AE (10 or 50 mg/kg/day) or amlodipine besylate (Am; 10 mg/kg/day) orally. Hypertension results in injury to several organs and can produce a significant increase in malondialdehyde (MDA) content as a result of lipid peroxidation and endothelial dysfunction. In this study, oral administration of AE and Am significantly reduced systolic blood pressure, organ weight index, and MDA content in tissues but increased significantly the plasma nitrite and nitrate concentrations. The endothelium-dependent relaxant activities of acetylcholine (10⁻¹⁰–10⁻³ M) in norepinephrine (NE)-precontracted aorta were increased in AE- and Am-treated rats. Particularly strong endothelium-dependent relaxant activities were observed in AE-treated (50 mg/kg) rats. The endothelium-independent relaxant activities of sodium nitroprusside (10⁻¹⁰–10⁻³ M) in NE-precontracted aorta were not changed. The results of this study suggest that AE has both antihypertensive and end-organ protective effects in SHR.
Acetylcholine ; Administration, Oral ; Amlodipine ; Animals ; Aorta ; Aralia* ; Blood Pressure ; Ethanol* ; Hypertension ; Lipid Peroxidation ; Malondialdehyde ; Nitroprusside ; Norepinephrine ; Organ Size ; Plasma ; Rats ; Rats, Inbred SHR*

Upper gastrointestinal bleeding is a common condition and has various clinical courses and prognosis. End stage renal disease (ESRD) patients receiving hemodialysis have a high risk of vascular complications and increased risk of ischemic colitis. A 59-year-old male patient with ESRD receiving hemodialysis visited due to hematemesis. After admission, he showed recurrent hematemesis and hypovolemic shock. Upper esophagogastroduodenoscopy revealed gastric ulcer bleeding and endoscopic hemostasis was successfully performed. Blood transfusion and norepinephrine was administered for hypovolemic shock during initial 3 days. Ten days later, he exhibited hematochezia. Sigmoidoscopy revealed necrotic ischemic colitis in sigmoid colon and segmental colectomy was performed. However, recurrent leakage and ischemia were developed in colon as well as small bowel, and he finally died after 55 hospital days in spite of additional operations. Here, we report a case of peptic ulcer bleeding in patient with ESRD who suffered a severe form of ischemic colitis with transmural necrosis.
Blood Transfusion ; Colectomy ; Colitis, Ischemic* ; Colon ; Colon, Sigmoid ; Endoscopy, Digestive System ; Gastrointestinal Hemorrhage ; Hematemesis ; Hemorrhage ; Hemostasis, Endoscopic ; Humans ; Ischemia ; Kidney Failure, Chronic* ; Male ; Middle Aged ; Necrosis ; Norepinephrine ; Peptic Ulcer ; Prognosis ; Renal Dialysis* ; Shock* ; Sigmoidoscopy ; Stomach Ulcer*

OBJECTIVETo compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction.

METHODSVentricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of β1-adrenoceptor (AR) and SERCA 2a were determined.

RESULTSCardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01).

CONCLUSIONSThe administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.

Adenylyl Cyclases ; metabolism ; Animals ; Blotting, Western ; Cardiac Output ; drug effects ; Cardiopulmonary Resuscitation ; Cyclic AMP ; metabolism ; Dopamine ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Enzyme-Linked Immunosorbent Assay ; Epinephrine ; blood ; Heart Ventricles ; drug effects ; metabolism ; physiopathology ; Hemodynamics ; drug effects ; Injections ; Male ; Myocardium ; enzymology ; pathology ; Norepinephrine ; blood ; Receptors, Adrenergic, beta-1 ; metabolism ; Sarcoplasmic Reticulum Calcium-Transporting ATPases ; metabolism ; Swine ; Swine, Miniature ; Up-Regulation ; drug effects

Resistant hypertension has for many decades been defined as difficult-to-treat hypertension in order to identify patients who may benefit from special diagnostic and/or therapeutic considerations. Recently, the term "refractory hypertension" has been proposed as a novel phenotype of antihypertensive failure, that is, patients whose blood pressure cannot be controlled with maximal treatment. Early studies of this phenotype indicate that it is uncommon, affecting less than 5% of patients with resistant hypertension. Risk factors for refractory hypertension include obesity, diabetes, chronic kidney disease, and especially, being of African origin. Patients with refractory are at high cardiovascular risk based on increased rates of known heart disease, prior stroke, and prior episodes of congestive heart failure. Mechanisms of refractory hypertension need exploration, but early studies suggest a possible role of heightened sympathetic tone as evidenced by increased office and ambulatory heart rates and higher urinary excretion of norepinephrine compared to patients with controlled resistant hypertension. Important negative findings argue against refractory hypertension being fluid dependent as is typical of resistant hypertension, including aldosterone levels, dietary sodium intake, and brain natriuretic peptide levels being similar or even less than patients with resistant hypertension and the failure to control blood pressure with use of intensive diuretic therapy, including both a long-acting thiazide diuretic and a mineralocorticoid receptor antagonist. Further studies, especially longitudinal assessments, are needed to better characterize this extreme phenotype in terms of risk factors and outcomes and hopefully to identify effective treatment strategies.
Aldosterone ; Blood Pressure ; Heart Diseases ; Heart Failure ; Heart Rate ; Humans ; Hypertension* ; Natriuretic Peptide, Brain ; Norepinephrine ; Obesity ; Phenotype ; Receptors, Mineralocorticoid ; Renal Insufficiency, Chronic ; Risk Factors ; Sodium, Dietary ; Spironolactone ; Stroke ; Sympathetic Nervous System ; Treatment Failure*

Ketamine is an anesthetic with hypertensive effects, which make it useful for patients at risk of shock. However, previous ex vivo studies reported vasodilatory actions of ketamine in isolated arteries. In this study, we reexamined the effects of ketamine on arterial tones in the presence and absence of physiological concentrations of 5-hydroxytryptamine (5-HT) and norepinephrine (NE) by measuring the isometric tension of endothelium-denuded rat mesenteric arterial rings. Ketamine little affected the resting tone of control mesenteric arterial rings, but, in the presence of 5-HT (100~200 nM), ketamine (10~100 µM) markedly contracted the arterial rings. Ketamine did not contract arterial rings in the presence of NE (10 nM), indicating that the vasoconstrictive action of ketamine is 5-HT-dependent. The concentration-response curves (CRCs) of 5-HT were clearly shifted to the left in the presence of ketamine (30 µM), whereas the CRCs of NE were little affected by ketamine. The left shift of the 5-HT CRCs caused by ketamine was reversed with ketanserin, a competitive 5-HT(2A) receptor inhibitor, indicating that ketamine facilitated the activation of 5-HT(2A) receptors. Anpirtoline and BW723C86, selective agonists of 5-HT(1B) and 5-HT(2B) receptors, respectively, did not contract arterial rings in the absence or presence of ketamine. These results indicate that ketamine specifically enhances 5-HT(2A) receptor-mediated vasoconstriction and that it is vasoconstrictive in a clinical setting. The facilitative action of ketamine on 5-HT(2A) receptors should be considered in ketamine-induced hypertension as well as in the pathogenesis of diseases such as schizophrenia, wherein experimental animal models are frequently generated using ketamine.
Animals ; Arteries ; Blood Pressure ; Humans ; Hypertension ; Ketamine* ; Ketanserin ; Mesenteric Arteries* ; Models, Animal ; Norepinephrine ; Rats* ; Receptor, Serotonin, 5-HT2A ; Schizophrenia ; Serotonin ; Shock ; Vasoconstriction

We present the case of a 38-year-old woman admitted to our outpatient clinic with accelerating back pain and fatigue following a kick to her back by her husband. Upon arrival, we detected ST segment elevation in the D1, aVL, and V2 leads and accelerated idioventricular rhythm. She had pallor and hypotension consistent with cardiogenic shock. We immediately performed coronary angiography and found a long dissection starting from the mid-left main coronary artery and progressing into the mid-left anterior descending (LAD) and circumflex arteries. She was then transferred to the operating room for surgery. A saphenous vein was grafted to the distal LAD. Since the patient was hypotensive under noradrenaline and dopamine infusions, she was transferred to the cardiovascular surgery intensive care unit on an extracorporeal membrane oxygenator and intra-aortic balloon pump. During follow-up, her blood pressure remained low, at approximately 60/40 mmHg, despite aggressive inotropic and mechanical support. On the second postoperative day, asystole and cardiovascular arrest quickly developed, and despite aggressive cardiopulmonary resuscitation, she died.
Accelerated Idioventricular Rhythm ; Adult ; Ambulatory Care Facilities ; Arteries ; Back Pain ; Blood Pressure ; Cardiopulmonary Resuscitation ; Coronary Angiography ; Coronary Vessels* ; Dopamine ; Fatigue ; Female ; Follow-Up Studies ; Heart Arrest ; Humans ; Hypotension ; Intensive Care Units ; Norepinephrine ; Operating Rooms ; Oxygenators, Membrane ; Pallor ; Saphenous Vein ; Shock, Cardiogenic ; Spouses ; Transplants

OBJECTIVETo compare the clinical efficacy on post-stroke insomnia between the low-frequency electric stimulation at the acupoints and the conventional western medication in the patients so as to explore the effect mechanism.

METHODSOne hundred and twenty patients of post-stroke insomnia were randomized into a low-frequency electric stimulation group, a medication group and a placebo group, 40 cases in each one. In the low-frequency electric stimulation group, the low-frequency pulse electric apparatus was applied to stimulate Dazhui (GV 14) and Shenshu (BL 23), once every day. The treatment for 15 days made one session and 2 sessions were required. In the medication group, estazolam was taken orally, 1 mg each time; and in the placebo group, the starch capsules were taken, one capsule each time; in the two groups the treatment was adopted before sleep every night, continuously for 15 days as one session, and 2 sessions were required. The levels of plasma 5-hydroxytryptamine (5-HT) and norepinephrine (NE) were compared before and after treatment in the patients of the three groups and: the efficacy was compared.

RESULTSIn the placebo group, 1 case was dropped out. The total effective rate was 95. 0% (38/40), 92. 5% (37/40) and 17. 9% (7/39) in the low-frequency electric stimulation group, the medication group and the placebo group respectively. The effects in the low-frequency electric stimulation group and the medication group were better apparently than that in the placebo group (both P<0. 01). The effect was not different significantly between the low-frequency electric stimulation group and the medication group (P>0. 05). The levels of plasma 5-HT and NE were not different significantly between before and after treatment in the placebo group. The level of plasma 5-HT was increased (both P<0. 05) and thelevel of NE was decreased (both P<0. 05) as compared with that before treatment in the low-frequency electric stimulation group and the medication group. But the differences were not significant between the two groups (P>0. 05).

CONCLUSIONThe low-frequency electric stimlaton a the acupoints is safe and effective in the treatment of post-stroke insomnia, which is similar to oral medication of estazolam. The outcome of the increase of plasma 5-HT level and the decrease of plasma NE level is probably one of the effect mechanisms.

Acupuncture Points ; Aged ; Aged, 80 and over ; Electric Stimulation ; Electroacupuncture ; Female ; Humans ; Male ; Middle Aged ; Norepinephrine ; blood ; Serotonin ; blood ; Sleep ; Sleep Initiation and Maintenance Disorders ; blood ; etiology ; physiopathology ; therapy ; Stroke ; blood ; complications ; physiopathology ; Treatment Outcome