Increase In Mean Arterial Pressure Research Articles

PREDICTION OF FLUID RESPONSIVENESS WITH CRYSTALLOID MINI-FLUID CHALLENGE IN CRITICALLY ILL PATIENTS

Background: The mini-fluid challenge test is a good predictor and has minimal limitations in determining fluid responsiveness in the critically ill. However, it primarily relies on colloid infusion. The availability of colloids may vary among hospitals in resource-limited countries, and they can be more expensive than crystalloid fluids. Objective: The study aimed to use crystalloids instead of colloids to predict fluid responsiveness. Methods: This study was conducted from August 2022 to February 2023 among patients with shock in the medical ICU to assess fluid responsiveness. Arterial and central venous catheters were used for the intravenous infusion and monitoring. Data were collected during two consecutive crystalloid mini-fluid challenges of 50 mL each in 1 minute, 100 mL in 2 minutes, and a standard fluid challenge of 300 mL over 15 minutes. The objective was to predict a stroke volume index (SVI) increase of > 10%. Diagnostic accuracy was evaluated using the Receiver Operating Characteristic (ROC) curve, and hemodynamic variables in the positive fluid challenge group were compared for different volume expansions. Results: Twenty-nine patients (62% males; median age, 75 years) were included, with 42 fluid challenge test events. Septic shock was the primary condition in 83% of the cases. The 50 mL crystalloid mini-fluid challenge showed an accuracy of 80% with a sensitivity of 69% and specificity of 100% at the cutoff level of SVI > 5%, Area Under ROC (AUROC)=0.79. In comparison, the 100 mL crystalloid mini-fluid challenge demonstrated an accuracy of 85% (sensitivity of 79% and specificity of 100%) at the cutoff level of SVI > 10% (AUROC= 0.89). In the positive fluid challenge group, administration of crystalloids led to a significant increase in mean arterial pressure and SVI, while other parameters remained comparable. Conclusions: A mini-fluid challenge test with 100 mL crystalloids can predict fluid responsiveness in critically ill patients. The best cutoff level was a change in SVI > 10% from baseline.

Age and Sex Differences in the Contribution of Mean Arterial Pressure to Pulse Pressure Before Middle Age.

A lower ability to buffer pulse pressure (PP) in the face of increasing mean arterial pressure (MAP) may underlie the disproportionate increase in systolic blood pressure (SBP) in women from young adulthood through middle-aged relative to men. To evaluate the contribution of MAP to the change in PP and pressure wave contour in men and women from young adulthood to middle age. Central pressure waveform was obtained from radial artery applanation tonometry in 312 hypertensive patients between 16 to 49 years (134 women, mean age 35 ± 9 years), 185 of whom were on antihypertensive treatment. Higher MAP levels (≥ 100 mmHg) were significantly associated with higher brachial and central SBP (P < 0.001), PP (P < 0.001), incident wave (P = 0.005), AP (P < 0.001), and PWV (P < 0.001) compared to lower MAP levels. The relationship between MAP and brachial PP (P < 0.001), central PP (P < 0.001), incident wave (P < 0.001), and AP (P < 0.01), but not PWV, strengthens with age. The age-related increase in the contribution of MAP to brachial PP (P < 0.001), central PP (P < 0.001), and incident wave (P < 0.001) was more prominent in women than in men beginning in the fourth decade. In multiple regression analyses, MAP remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of age, heart rate, and antihypertensive treatment. In turn, age remained a significantly stronger predictor of central PP and incident wave in women than in men, independent of MAP, heart rate, and antihypertensive treatment. Women of reproductive age showed a steeper increase in PP with increasing MAP, despite comparable increases in arterial stiffness in both sexes. The difference was driven by a greater contribution of MAP to the forward component of the pressure wave in women.

The Role of Interleukin-6 in Regulating Glomerular Filtration Rate during Angiotensin II and High Salt Conditions

Previous results demonstrate that interleukin-6 (IL-6) increases mean arterial pressure (MAP) during Angiotensin II (Ang II)-salt hypertension. In addition, albumin excretion was lower in IL-6 knockout mice (KO) when compared to wild-type (WT). This study investigated the role of IL-6 on regulating glomerular filtration rate (GFR), renal plasma flow (RPF) and MAP in WT and IL-6 KO mice treated with a slow pressor dose of Ang II (200 ng/kg/min) +/- 6% high-salt (HS) diet. Male C57BL6 and IL-6 KO mice (12 weeks old) were treated with Ang II +/- 6% HS diet for 12 – 14 days. Mean arterial pressure, RPF and GFR were measured in anesthetized mice. MAP was 130 ± 7 mmHg and 91 ± 4 mmHg in control WT and IL-6 KO mice, respectively. Ang II treatment increased MAP in WT (153 ± 5 mmHg) and no change in IL-6 KO (83 ± 4 mmHg) mice. Ang II + 6% HS increased MAP to 150 ± 11 mmHg in WT and 93 ± 4 mmHg in IL-6 KO mice. Baseline RPF was 1822 ± 229 and 1912 ± 402 ml/min/g in control WT and IL-6 KO mice, respectively. Ang II treatment increased RPF in WT (3156 ± 753 ml/min/g), while lowering RPF in IL-6 KO (1648 ± 422 ml/min/g) mice. RPF during Ang II + 6% HS treatment was decreased in WT (1095 ± 305 ml/min/g) and IL-6 KO (1133 ml/min/g) mice. GFR was 756 ± ml/min/g and 788 ± ml/min/g in control WT and IL-6 KO mice, respectively. Ang II increased GFR in WT (1009 ± 63 ml/min/g) and no change in IL-6 KO (756 ± 23 ml/min/g). Ang II + 6% HS increased GFR in WT (1095 ± 146 ml/min/g) and no change in GFR of IL-6 KO (540 ± 207 ml/min/g) mice. Our results suggest that IL-6 reduces MAP during baseline, Ang II, and Ang II + 6% HS. The absence of IL-6 prevented increases in MAP, RPF and GFR during Ang II treatment. Our data also suggest that IL-6 contributes to increased MAP and GFR during Ang II + 6% HS treatment. K01HL092593-05. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Deletion of Piezo2 from renal Foxd1+ stromal progenitors and descendent cells results in abnormal mesangial development and sex-specific differences in kidney function

Piezo2 is a mechanically activated ion channel recently identified in glomerular mesangial cells and renin+ juxtaglomerular (JG) cells. Despite several studies which confirm this localization of Piezo2 in the kidney, the function of Piezo2 in these cells remains ambiguous. In the current study, we hypothesized that loss of Piezo2 in mesangial and JG cells would result in abnormal glomerular development during nephrogenesis and impaired salt and water balance in adult mice. To test this hypothesis, we generated mutant mice lacking Piezo2 in Foxd1+ stromal progenitors and their cell lineages, which include mesangial and JG cells. Kidney morphology was assessed by immunofluorescent staining and z-stack confocal microscopy during late nephrogenesis (post-natal day 0, P0) and following maturation of the nephron (P20) in wild-type (Piezo2fl/fl, n=3), heterozygous (Foxd1GC/+Piezo2fl/+, n=3), and mutant (Foxd1GC/+Piezo2fl/fl, n=3) mice. In adult male and female mice (n=2/genotype/sex), blood pressure was measured by tail cuff (CODA Systems) between 1-4pm following 3 days of acclimation. In a separate group of control and mutant male and female mice (8-10 weeks, n=3-5/group/sex), a 4-hour saline challenge (i.p. 10% body weight) was performed to assess diuresis and natriuresis. At P0, we found that deletion of Piezo2 from Foxd1+ stromal progenitors and their cell lineages resulted in the abnormal distribution of mesangial cells within glomeruli, such that the mesangial area appears compressed compared to control or heterozygous mice. This phenotype was exacerbated in mutant mice by P20. In adult mice, female mutants had an increase in daytime mean arterial pressure (~10mmHg, mean 79 vs 88) compared to female controls. Cumulative urine excretion (4 hours, percent injected) was decreased in females compared to males, regardless of genotype (p&lt;0.001). Further, female mutant mice had a delayed diuresis response compared to control (2 hour, mean 16% vs 28% cumulative urine volume). However by 4 hours following a saline bolus both groups were similar. Taken together, these data indicate that deletion of Piezo2 in Foxd1+ stromal progenitors results in impairments in mesangial cell development during nephrogenesis and alterations in water and salt balance in adult female mice. Understanding the sex-specific roles of Piezo2 in kidney development and physiology is critical to identify the role of mechanosensation on renal homeostasis. NIH R01DK121014 to LO. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Estrogen stimulates fetal vascular endothelial growth factor expression and microvascularization.

We recently showed that the ratio of capillaries/myofibers in skeletal muscle, which accounts for 80% of insulin-directed glucose uptake and metabolism, was reduced in baboon fetuses in which estrogen was suppressed by maternal letrozole administration. Since vascular endothelial growth factor (VEGF) promotes angiogenesis, the present study determined the impact of estrogen deprivation on fetal skeletal muscle VEGF expression and capillary development and long-term vascular and metabolic function in 4-8 year old adult offspring. Maternal baboons were untreated or treated with letrozole or letrozole plus estradiol on days 100-164 of gestation (term = 184 days). Skeletal muscle VEGF protein expression was suppressed by 45% (P < 0.05) and correlated (P = 0.01) with a 47% reduction (P < 0.05) in number of capillaries per myofiber area in fetuses of baboons in which serum estradiol levels were suppressed 95% (P < 0.01) by letrozole administration. The reduction in fetal skeletal muscle microvascularization was associated with a 52% decline (P = 0.02) in acetylcholine-induced brachial artery dilation and 23% increase (P = 0.01) in mean arterial blood pressure in adult progeny of letrozole-treated baboons and restored to normal by letrozole plus estradiol. The present study indicates that estrogen upregulates skeletal muscle VEGF expression and systemic microvessel development within the fetus as an essential programming event critical for ontogenesis of systemic vascular function and insulin sensitivity/glucose homeostasis after birth in primate offspring.

Microglia Mediate Hypertension and Autonomic Dysfunction through Kinin B1 Receptor Activation

Reactive oxygen species and proinflammatory cytokines in the central nervous system can induce or exacerbate hypertension (HTN) and result in autonomic dysfunction. During HTN, activated microglia modulates autonomic neural activity in the paraventricular nucleus of the hypothalamus (PVN) by regulating neuroinflammation and blood pressure. We previously reported that enhanced kinin B1 receptor (B1R) expression in the brain is associated with increased neuroinflammation and autonomic dysfunction leading to the development of HTN. However, the functional role of B1R within microglia and signaling mechanisms during HTN have yet to be investigated. In this study, we tested the hypothesis that B1R blockade will reduce oxidative stress and mitochondrial dysfunction in microglia, resulting in an attenuation of hypertension and improved autonomic function. Male and female C57BL/6NJ wild-type (WT) and B1R global gene deficient mice (B1RKO) were administered angiotensin II (Ang II) (600 ng/kg/min; SC, 2 weeks) or saline (vehicle) via osmotic minipumps. Ang II infusion significantly increased mean arterial pressure (radiotelemetry) in WT mice (145 ±13 mmHg vs. 103 ±6, n=6, p&lt;0.01), which was attenuated in B1RKO mice. Ang II induced HTN resulted in dysautonomia as indicated by significantly increased plasma norepinephrine levels (p&lt;0.05, n=6) and decreased spontaneous baroreceptor reflex sensitivity (p&lt;0.05, n=6). This further suggests that B1R contributes to impaired autonomic and baroreflex functions in HTN. In addition, CX3CR1 expression in the PVN revealed that microglia-neuron interactions may be increased during HTN. TMEM119 immunofluorescence revealed significant morphological changes in microglia in the PVN of Ang II infused mice compared to saline controls (p&lt;0.05, n=3). To further define the role of microglia, we cultured primary microglia from neonatal mice and found that Ang II induces mitochondrial oxidative stress (MitoSOX) and decreases mitochondrial membrane potential (TMRE) (p&lt;0.01, n=4), however use of B1R specific antagonist SSR240612 was able to reduce these responses. This data coincides with previous data published in primary hypothalamic neurons. To then explore the role of neuron-microglia interactions following Ang II stimulation, we established a direct co-culturing method and through immunocytochemistry, confirmed that levels of oxidative stress and inflammation were significantly increased in our co-culture model compared to when cultured individually (p&lt;0.05, n=3). Pretreatment with B1R antagonist was able to attenuate these effects. This data indicates that autonomic and mitochondrial dysfunction may be regulated, in part, through the kinin B1 receptor in microglia and that neuron-microglia interactions can enhance these effects. This allows us to believe that B1R blockade may serve as a potential therapeutic target for HTN induced mitochondrial and autonomic dysfunction. This study was supported by the NHLBI/NIH 5R01HL153115 (S. Sriramula). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Angiotensin II-Induced Heart Failure Disrupts Cardiac Sympathetic Innervation

About 26 million people worldwide live with heart failure (HF), and 25% have hypertension (HTN) as the primary cause. These patients have a high risk for cardiac arrhythmias and sudden cardiac death. Autonomic dysfunction and sympathetic hyperactivity accompany these diseases, and sympathetic activation is crucial for triggering fatal arrhythmias. However, changes in cardiac sympathetic innervation in HF are not well understood. We hypothesized that cardiac sympathetic innervation is disrupted in a mouse model of Angiotensin II (AngII)-induced HF. To test this hypothesis, C57BL6 male (N=6, 10) and female (N=6, 10) mice 12-20 weeks old were implanted with minipumps releasing either AngII (712ng/min/Kg, N=6-10) or saline (N=6-10) for 4 weeks. HTN and cardiac function were measured with tail cuff quantification and echocardiography, respectively. Fibrosis was assessed using Trichrome staining. Cardiac sympathetic innervation was quantified using immunohistochemistry for Tyrosine Hydroxylase (TH). Cardiac norepinephrine (NE) was measured by High-Performance Liquid Chromatography with electrochemical detection. Values were compared with a Student’s unpaired t-test unless noted, data were represented as mean ± SD, and significance was defined as p&lt;0.05. AngII-treated mice had significantly increased mean arterial pressure (Saline 91.0±15.6 vs. AngII 152.9±22.3 mmHg, p&lt;0.05, N=6-7) 7 days after minipump implantation. Four weeks of AngII treatment led to HF, as indicated by reduced ejection fraction (Saline 54.8±3.8 vs. AngII 43.1±8.2 %, p&lt;0.05, N=10) and fractional shortening (Saline 14.3±2.6 vs. AngII 10.6±3.3 %, p&lt;0.05, N=10). Cardiac hypertrophy was also observed in AngII-treated mice and was reflected by increased heart weight to body weight ratio (Saline 5.2±0.2 vs. AngII 7.7±1.0, p&lt;0.05, N=6). Fibrosis was detected in the intraventricular septum (IVS) and left ventricle (LV) of AngII-treated mice. TH+ fibers in the LV and IVS were decreased significantly (LV: Saline 0.6±0.2 vs. AngII 0.4±0.1 %; IVS: Saline 0.3±0.1 vs. AngII 0.09±0.04 %, p&lt;0.05, N=6), while no differences were detected in the right ventricle (Saline 1.1±0.2 vs. AngII 0.8±0.3 %, P&gt;0.05, N=6). In addition, the subepicardium-subendocardium (EPI-ENDO) gradient was altered (EPI: Saline 0.9±0.2 vs. AngII 0.8±0.3 %, P&gt;0.05; ENDO: Saline 0.3±0.05 vs. AngII 0.1±0.1 %, p&lt;0.05; EPI:ENDO ratio: Saline 2.7±0.7 vs. AngII 15.7±16.8, p&lt;0.05, Mann-Whitney test, N=6). A significant decrease in NE content accompanied the loss of TH+ fibers in the LV (LV: Saline 3.9±0.4 vs. AngII 1.6±0.2 pmol/mg, p&lt;0.05; RV: Saline 4.4±1.0 vs. AngII 3.8±0.8 pmol/mg, P&gt;0.05, N=4-6). Our data demonstrate that AngII-induced HF disrupts cardiac sympathetic nerve density, distribution, and NE content, confirming our initial hypothesis. This evidence contrasts with sympathetic hyperactivity seen in cardiac diseases. Future studies will assess the overall cardiac innervation and, determine whether the loss of TH+ fibers is due to a reduced sympathetic innervation after cardiac remodeling or the cholinergic transdifferentiation of TH+ fibers. A better understanding of the cardiac sympathetic nervous system in HF is imperative to deciphering the mechanistic changes to cardiac innervation in disease, and may help to develop and implement novel and precise neuromodulatory therapies for patients with autonomic imbalance. Supported by NIH R01 HL146833 to Dr. Habecker. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A mathematical model to assess the effects of COVID-19 on the cardiocirculatory system

Impaired cardiac function has been described as a frequent complication of COVID-19-related pneumonia. To investigate possible underlying mechanisms, we represented the cardiovascular system by means of a lumped-parameter 0D mathematical model. The model was calibrated using clinical data, recorded in 58 patients hospitalized for COVID-19-related pneumonia, to make it patient-specific and to compute model outputs of clinical interest related to the cardiocirculatory system. We assessed, for each patient with a successful calibration, the statistical reliability of model outputs estimating the uncertainty intervals. Then, we performed a statistical analysis to compare healthy ranges and mean values (over patients) of reliable model outputs to determine which were significantly altered in COVID-19-related pneumonia. Our results showed significant increases in right ventricular systolic pressure, diastolic and mean pulmonary arterial pressure, and capillary wedge pressure. Instead, physical quantities related to the systemic circulation were not significantly altered. Remarkably, statistical analyses made on raw clinical data, without the support of a mathematical model, were unable to detect the effects of COVID-19-related pneumonia in pulmonary circulation, thus suggesting that the use of a calibrated 0D mathematical model to describe the cardiocirculatory system is an effective tool to investigate the impairments of the cardiocirculatory system associated with COVID-19.

Use of Inotropes and vasopressors in Septic Shock: When, Why, and How?

Septic shock, a severe and sometimes fatal condition caused by systemic infection, demands immediate and focused therapies to restore hemodynamic stability and prevent organ failure. The use of vasopressors and inotropes has become the foundation in the treatment of septic shock, with the goal of reversing the vasodilatory condition and increasing cardiac contractility.&#x0D; Vasopressors are an effective class of medications that cause vasoconstriction and hence increase mean arterial pressure (MAP). Norepinephrine is recommended as the first-line agent to use in septic shock. However, many medications have both vasopressor and inotropic actions, distinguishing them from inotropes, which increase heart contractility.&#x0D; Inotropes work by increasing cardiac contractility and thereby increasing cardiac output. Dobutamine is still the mainstay of treatment based on the latest SCCM guidelines.&#x0D; This review provides a comprehensive overview of the rationale, indications, doses and major side effects surrounding the administration of these pharmacological agents in septic shock.&#x0D; Our team extensively explored various databases regarding this subject. We concluded that the most trustworthy sources for our study were articles indexed in PubMed. We thoroughly examined these articles and synthesized the information within our review.&#x0D; We recommend that more trials are needed to compare the effectivity of dobutamine compared to other inotropes in the setting of septic shock as the latest guidelines are based on a shortage of randomized control trials. Also the literature should emphasize the importance of continuous hemodynamic monitoring during vasopressor therapy, highlighting the necessity for personalized changes to reach and maintain target blood pressure targets.

The effect of vasopressor agents on pressure injury development in intensive care patients

BackgroundVasopressors are life-saving agents that increase mean arterial pressure. The pharmacodynamic features of these agents and previous studies suggest that vasopressors may be an essential risk factor in developing pressure injuries. ObjectiveThis study aimed to examine the effect of vasopressors in medical-surgical intensive care patients on pressure injury development. Design and settingsThis retrospective and correlational study was conducted between March 2021- May 2022. The electronic patient data were obtained from 148 surgical and medical patients exposed to vasopressor agents in the intensive care unit. Data on patients' demographic and clinical characteristics were evaluated using descriptive statistical methods (number, percentage, mean, standard deviation). Logistic regression modelling was used to assess independent relationships with pressure injury risk; results are reported as odds ratios (OR) and 95% confidence intervals (CI). ResultsAll patients were given norepinephrine agents, and dopamine infusion secondary to norepinephrine was found in only 28.3 % of patients (n = 42). Pressure injury incidence was 43.2 % (n = 64). Duration of norepinephrine infusion was recognized as an independent risk factor for ICU-acquired pressure injury development (OR 1.22, 95 % CI 1.11–1.35), while a medical admission diagnosis (instead of surgical) was protective against pressure injury risk (OR 0.24, 95 % CI 0.10–0.59). ConclusionThis study indicated that duration of norepinephrine infusion is a significant risk factor for pressure injury development. Implications for clinical practiceAlthough norepinephrine use cannot be avoided entirely, its administration may be an early warning for nurses to increase pressure injury prevention strategies. Skin evaluation should be performed more frequently, and preventive strategies should be implemented meticulously.This study was registered on clincialtrials.gov (Identifier: NCT06163352)

Analysis of haemodynamics surrounding blood transfusions after the arterial switch operation: a pilot study utilising real-time telemetry high-frequency data capture.

Packed red blood cell transfusions occur frequently after congenital heart surgery to augment haemodynamics, with limited understanding of efficacy. The goal of this study was to analyse the hemodynamic response to packed red blood cell transfusions in a single cohort, as "proof-of-concept" utilising high-frequency data capture of real-time telemetry monitoring. Retrospective review of patients after the arterial switch operation receiving packed red blood cell transfusions from 15 July 2020 to 15 July 2021. Hemodynamic parameters were collected from a high-frequency data capture system (SickbayTM) continuously recording vital signs from bedside monitors and analysed in 5-minute intervals up to 6 hours before, 4 hours during, and 6 hours after packed red blood cell transfusions-up to 57,600 vital signs per packed red blood cell transfusions. Variables related to oxygen balance included blood gas co-oximetry, lactate levels, near-infrared spectroscopy, and ventilator settings. Analgesic, sedative, and vasoactive infusions were also collected. Six patients, at 8.5[IQR:5-22] days old and weighing 3.1[IQR:2.8-3.2]kg, received transfusions following the arterial switch operation. There were 10 packed red blood cell transfusions administered with a median dose of 10[IQR:10-15]mL/kg over 169[IQR:110-190]min; at median post-operative hour 36[IQR:10-40]. Significant increases in systolic and mean arterial blood pressures by 5-12.5% at 3 hours after packed red blood cell transfusions were observed, while renal near-infrared spectroscopy increased by 6.2% post-transfusion. No significant changes in ventilation, vasoactive support, or laboratory values related to oxygen balance were observed. Packed red blood cell transfusions given after the arterial switch operation increased arterial blood pressure by 5-12.5% for 3 hours and renal near-infrared spectroscopy by 6.2%. High-frequency data capture systems can be leveraged to provide novel insights into the hemodynamic response to commonly used therapies such as packed red blood cell transfusions after paediatric cardiac surgery.

Evaluation of Electrocardiogram Parameters and Heart Rate Variability During Blood Pressure Elevation by Phenylephrine in Cirrhotic Rats.

Cirrhotic cardiomyopathy is a myocardial disease that may go undetected in the early stages due to peripheral vasodilatation. The aim of the study was to evaluate the electrocardiogram (ECG) and heart rate variability (HRV) after raising blood pressure by phenylephrine injection in rats with liver cirrhosis. Twenty male Sprague-Dawley rats were divided into the Sham and common bile duct ligation (CBDL) groups. After 44days, animals were anesthetized and the right femoral artery and vein catheterized. After a steady-state period, a bolus injection of phenylephrine (PHE, 10μg/μl/IV, baroreflex maneuver) was followed by a slow injection of PHE (100μg/ml/5min/IV, sustained maneuver). Rapid and slow injections of PHE resulted in a greater increase in mean arterial pressure (MAP) and a weaker bradycardia response in the CBDL group than in the Sham group. ECG analysis showed increased QT, QTc, JT, and T peak to T end in the CBDL group, which remained unchanged after PHE injection. On the other hand, the parasympathetic indices of the HF band and RMSSD, and the sympathetic index of the LF band after PHE injection were lower in the CBDL group than in the Sham group.ECG data indicated prolonged ventricular depolarization and repolarization, independent of blood pressure levels in cirrhosis. On the other hand, after PHE injection, the parasympathetic and sympathetic components of HRV decreased, regardless of the duration of elevated blood pressure. We suggest that HRV analysis can provide a useful approach to assess cardiac dysfunction associated with elevated blood pressure in cirrhosis.

Angiotensin ii therapy in refractory septic shock: which patient can benefit most? A narrative review.

Patients with septic shock who experience refractory hypotension despite adequate fluid resuscitation and high-dose noradrenaline have high mortality rates. To improve outcomes, evidence-based guidelines recommend starting a second vasopressor, such as vasopressin, if noradrenaline doses exceed 0.5 µg/kg/min. Recently, promising results have been observed in treating refractory hypotension with angiotensin II, which has been shown to increase mean arterial pressure and has been associated with improved outcomes. This narrative review aims to provide an overview of the pathophysiology of the renin-angiotensin system and the role of endogenous angiotensin II in vasodilatory shock with a focus on how angiotensin II treatment impacts clinical outcomes and on identifying the population that may benefit most from its use.

The potential of methylene blue in treating septic shock: Is it worth a shot?

Shock is a circulatory failure that results in insufficient oxygen supply to cells. Septic shock is the most common variety in patients admitted to the Intensive Care Unit (ICU) and is a fatal condition that accounts for a considerable number of deaths in the ICU. [1, 2]. Treatment of septic shock consists of a triad that comprises hemodynamic resuscitation via crystalloid, vasopressor infusion and antibiotic delivery within the first hour of recognition [2]. Despite the evidence that these measures help reduce mortality, the percentage of death remains greater than 40%, necessitating the requirement for alternative treatment strategies [2]. Research shows that methylene blue significantly increases mean arterial pressure (MAP) and systemic vascular resistance (SVR).Furthermore, treatment with methylene blue aids in the tapering of vasopressors [3]. In a recent single-centre randomised control trial including patients suffering from septic shock, Ibarra-Estrada et al. Investigated the effect of early adjuvant methylene blue on time to vasopressor discontinuation. They discovered that in comparison to the control group, patients who were administered methylene blue had decreased time to vasopressor discontinuation with no adverse but rather had a shorter length of ICU and hospital stay [4]. Another trial by R. Ismail et al. involving preterm neonates with refractory septic shock reported similar findings where methylene blue led to a significant rise in arterial blood pressure, reducing the need for norepinephrine [5]. In addition, pooled data from a systematic review and meta-analysis shows that the use of MB in conjunction with vasopressors dramatically reduced mortality in patients with vasodilatory shock. These findings suggest that methylene blue has favourable outcomes in treating septic shock. Due to limited data, more research is required to compare the efficacy of methylene blue in different types of shock states and in different subgroups such as neonates, adolescents, adults and the elderly population. At this stage, more evidence regarding the short-term and long-term benefits and possible side effects of using methylene blue is also required, to allow physicians to be able to incorporate it in regular treatment protocols when practicing evidence-based medicine. Newer studies could help shed some light on appropriate dosing regimens and discover populations that would reap the most benefits from its use. Accurate conclusions, drawn via systematic reviews and meta-analyses including newer large-scale multi-centred clinical trials might be just what is needed to enhance the already existing treatment regimens for shock.

Cold stimulation of the oral cavity redistributes blood towards the brain in healthy volunteers.

The aim of this study was to analyze cold stimulation-induced changes in cerebral and cardiac hemodynamics. Upon ingestion of an ice cube, the changes in resistance index, mean flow velocity and flow index of the middle cerebral arteries (MCA) were assessed using transcranial Doppler sonography. Extracranial duplex sonography was used to measure the mean flow velocity and resistance index of the right internal carotid artery (ICA). The change in mean arterial pressure, heart rate, root mean square of successive differences (RMSSD) and end-tidal carbon dioxide pressure were analyzed additionally. These changes were compared to sham stimulation. Compared with sham stimulation, cooling of the oral cavity resulted in significant changes in cerebral and cardiac hemodynamics. The cold stimulation decreased the resistance index in the MCA (-4.5% ± 5.4%, p < 0.0001) and right ICA (-6.3% ± 15.6%, p = 0.001). This was accompanied by an increase in mean flow velocity (4.1% ± 8.0%, p < 0.0001) and flow index (10.1% ± 43.6%, p = 0.008) in the MCA. The cardiac effects caused an increase in mean arterial pressure (1.8% ± 11.2%, p = 0.017) and RMSSD (55% ± 112%, p = 0.048), while simultaneously decreasing the heart rate (-4.3% ± 9.6%, p = 0.0001). Cooling of the oral cavity resulted in substantial changes in cerebral and cardiac hemodynamics resulting in a blood flow diversion to the brain.

Physiologic measurements of cognitive load in clinical reasoning.

Cognitive load is postulated to be a significant factor in clinical reasoning performance. Monitoring physiologic measures, such as heart rate variability (HRV) may serve as a way to monitor changes in cognitive load. The pathophysiology of why HRV has a relationship to cognitive load is unclear, but it may be related to blood pressure changes that occur in a response to mental stress. Fourteen residents and ten attendings from Internal Medicine wore Holter monitors and watched a video depicting a medical encounter before completing a post encounter form used to evaluate their clinical reasoning and standard psychometric measures of cognitive load. Blood pressure was obtained before and after the encounter. Correlation analysis was used to investigate the relationship between HRV, blood pressure, self-reported cognitive load measures, clinical reasoning performance scores, and experience level. Strong positive correlations were found between increasing HRV and increasing mean arterial pressure (MAP) (p=0.01, Cohen's d=1.41). There was a strong positive correlation with increasing MAP and increasing cognitive load (Pearson correlation 0.763; 95 % CI [; 95 % CI [-0.364, 0.983]). Clinical reasoning performance was negatively correlated with increasing MAP (Pearson correlation-0.446; 95 % CI [-0.720,-0.052]). Subjects with increased HRV, MAP and cognitive load were more likely to be a resident (Pearson correlation-0.845; 95 % CI [-0.990, 0.147]). Evaluating HRV and MAP can help us to understand cognitive load and its implications on trainee and physician clinical reasoning performance, with the intent to utilize this information to improve patient care.

Interindividual variability in cold-pressor pain sensitivity is not explained by peripheral vascular responding and generalizes to a C-nociceptor-specific pain phenotype.

Pain sensitivity of healthy subjects in the cold-pressor (CP) test was proposed to be dichotomously distributed and to represent a pain sensitivity trait. Still, it has not been systematically explored which factors influence this pain sensitivity readout. The aim of this study was to distinguish potential contributions of local tissue-related factors such as perfusion and thermoregulation or gain settings in nociceptive systems. Cold-pressor-sensitive and CP-insensitive students screened from a medical student laboratory course were recruited for a CP retest with additional cardiovascular and bilateral local vascular monitoring. In addition, comprehensive quantitative sensory testing according to Deutscher Forschungsverbund Neuropathischer Schmerz standards and a sustained pinch test were performed. Cold pressor was reproducible across sessions (Cohen kappa 0.61 ± 0.14, P < 0.005). At 30 seconds in ice water, CP-sensitive subjects exhibited not only more pain (78.6 ± 26.3 vs 29.5 ± 17.5, P < 0.0001) but also significantly stronger increases in mean arterial blood pressure (12.6 ± 9.3 vs 5.6 ± 8.1 mm Hg, P < 0.05) and heart rate (15.0 ± 8.2 vs 7.1 ± 6.2 bpm, P < 0.005), and lower baroreflex sensitivity, but not local or vasoconstrictor reflex-mediated microcirculatory responses. Cold-pressor-sensitive subjects exhibited significantly lower pain thresholds also for cold, heat, and blunt pressure, and enhanced pain summation, but no significant differences in Aδ-nociceptor-mediated punctate mechanical pain. In conclusion, differences in nociceptive signal processing drove systemic cardiovascular responses. Baroreceptor activation suppressed pain and cardiovascular responses more efficiently in CP-insensitive subjects. Cold-pressor sensitivity generalized to a pain trait of C-fiber-mediated nociceptive channels, which was independent of local thermal and vascular changes in the ice-water-exposed hand. Thus, the C-fiber pain trait reflects gain setting of the nociceptive system.

Comparison of Postoperative Analgesic Effect of Dexmedetomidine and Morphine as an Adjuvant to Intrathecal Bupivacaine in Infraumbilical Surgeries: A Randomised Clinical Trial

Introduction: Regional anaesthesia is the standard technique for lower limb infraumbilical procedures. To provide a better analgesic profile, adjuvants are added to local anaesthetics to enhance their action. Opioids have been used as an adjuvant for a long-time. With evolving pharmacology, various drugs satisfy the criteria of being an adjuvant. One such drug is Dexmedetomidine, a novel alpha-2 agonist. Aim: To compare the duration of analgesia of intrathecal Morphine and Dexmedetomidine as an adjuvant to bupivacaine in a subarachnoid block for lower limb infraumbilical surgeries. Materials and Methods: In this randomised clinical, doubleblinded study conducted in a multispecialty hospital over the period of June 2020 to February 2021, 70 patients were randomly divided into two groups: Group M received Morphine 125 µg, and Group D received dexmedetomidine 5 µg as an adjuvant to 15 mg of 0.5% hyperbaric bupivacaine. The primary outcome was to compare the duration of postoperative analgesia. The secondary results assessed the block characteristics, haemodynamic parameters, rescue analgesic consumption, sedation score, and side-effects like bradycardia, hypotension, nausea, vomiting, pruritus, and respiratory depression. Data was spread in an Excel sheet and descriptive analysis done. Normally distributed continuous variables were compared using a Student’s t-test, and discrete variables were compared using a Chi-square test. A p-value of &lt;0.05 was considered significant. Results: Both groups were similar with respect to age, sex, body mass index, American Society of Anaesthesiologists grading, and duration of surgery. The duration of analgesia was 956.97±120.043 minutes in group M and 392.83±50.354 minutes in group D (p-value &lt;0.001). The total consumption of paracetamol was 1984.71±499.111 mg in group M and 3543.86±406.17 mg in group D. The onset and regression were significantly faster in group D. There was significant hypotension and bradycardia up to the 40th minute and an increase in heart rate, respiratory rate, and mean arterial pressure between 5-7 hours in group D. The sedation score was more in group D for the initial two hours. Postoperatively, the incidence of nausea, vomiting, and pruritus was more in group M. Conclusion: It can be concluded that 125 µg of intrathecal morphine is a better adjuvant to spinal bupivacaine, providing excellent postoperative analgesia compared to 5 µg of intrathecal dexmedetomidine. However, dexmedetomidine had more incidence of hypotension, bradycardia, and sedation when compared to morphine intrathecally.

Comparison of esketamine versus dexmedetomidine for attenuation of cardiovascular stress response to double-lumen tracheal tube intubation: a randomized controlled trial.

The insertion of a double-lumen tracheal tube may cause a transient but more intense sympathetic response. We examined the effects of esketamine vs. dexmedetomidine as an adjuvant to anesthesia induction to blunt double lumen tracheal (DLT) intubation induced cardiovascular stress response. In a randomized, double-blind trial, 78 adult patients scheduled for elective thoracotomy under general anesthesia requiring DLT intubation were enrolled. The patients were randomly divided into three groups: each group received one of the following drugs prior to induction of anesthesia: dexmedetomidine 0.8 µg/kg (Group A), esketamine 0.5 mg/kg (Group B), or normal saline (group C). The primary outcome was the incidence of a DLT intubation-related cardiovascular stress response, defined as an increase in mean arterial pressure or heart rate of >30% above the baseline values. The secondary outcomes were changes in hemodynamic and cardiac function. The incidence of the response to cardiovascular stress was 23.1%, 30.8%, and 65.4% in groups A, B, and C, respectively. There was a significant decrease in intubation response in groups A and B in comparison with group C (P < 0.01); however, there was no significant difference between group A and group B (P > 0.05). Following the drug infusion and the induction of anesthesia, there was a significant decrease in HR and cardiac output in group A compared with group B. In contrast, no significant differences were observed in the left ventricular ejection fraction or in stroke volume between the three groups during induction of anesthesia. Esketamine 0.5 mg/kg and dexmedetomidine 0.8 µg/kg attenuate cardiovascular stress responses related to DLT intubation. As adjuvants to etomidate induction, they do not impair cardiac function (ChiCTR1900028030).

Argipressin-norepinephrine association in the treatment of septic shock: the use of the polydistrectual resistance index as an assessment of vascular compliance

IntroductionThe hemodynamic management of septic patients involves initial fluid therapy, followed by the use of vasoconstrictors in case of treatment failure. The latest Surviving Sepsis Campaign guidelines suggest the synergistic use of argipressin in addition to norepinephrine when hemodynamic optimization is not achieved with norepinephrine alone.MethodsIn our single-center retrospective observational study, the primary endpoint is the safety of initial norepinephrine-argipressin association treatment, assessed through a reduction in Resistance Index. Our secondary endpoint includes the efficacy of this combination, measured by an increase in Mean Arterial Pressure and a reduction in Resistance Index as an indicator of organ perfusion. The Resistance Index (RI) is evaluated through Power Doppler ultrasound. RI is crucial for assessing multi-district vascular tone and multiorgan perfusion. Patients were categorized into three groups based on their treatment. In Group 1, we analyzed patients treated with norepinephrine alone in incremental doses; in Group 2, we analyzed patients receiving the initial norepinephrine-argipressin association treatment (norepinephrine 0.05 mcg/kg/min-argipressin 0.03 IU/min); in the third group (Group 3), we analyzed patients given argipressin (0.03 IU/min) after norepinephrine (&amp;lt;0.10–0.25≥ mcg/kg/min) to stabilize their hemodynamics (MAP &amp;gt; 65 mmHg). RI measurements were taken in the Renal Artery (ARE), Radial Artery (AR), Central Retinal Artery (CRA), and Superior Mesenteric Artery (AMS) at four different time points: T0 before vasopressor therapy, T1 at 1 h, T2 at 24 h, and T3 at 48 h after vasopressor infusion.ResultsA total of 48 patients were divided into three groups: 17 patients in Group 1, 16 in Group 2, and 15 in Group 3. In Group 1, an increase in Mean Arterial Pressure (MAP) was observed, but there was an increase in RIs in the right CRI and left ARE. In Group 2, there was an improvement in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR. In Group 3, there was an increase in MAP and a reduction in RIs in the right/left CRI, left ARE, AMS, and right AR.ConclusionEarly norepinephrine-argipressin association treatment appears to be a valid strategy for hemodynamic optimization in this patient population.