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Physiological Reports Oct 2016Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe...
Intact cerebral blood flow (CBF) is essential for cerebral metabolism and function, whereas hypoperfusion in relation to hypovolemia and hypocapnia can lead to severe cerebral damage. This study was designed to assess internal carotid artery blood flow (ICA-BF) during simulated hypovolemia and noninvasive positive pressure ventilation (PPV) in young healthy humans. Beat-by-beat blood velocity (ICA and aorta) were measured by Doppler ultrasound during normovolemia and simulated hypovolemia (lower body negative pressure), with or without PPV in 15 awake subjects. Heart rate, plethysmographic finger arterial pressure, respiratory frequency, and end-tidal CO (ETCO) were also recorded. Cardiac index (CI) and ICA-BF were calculated beat-by-beat. Medians and 95% confidence intervals and Wilcoxon signed rank test for paired samples were used to test the difference between conditions. Effects on ICA-BF were modeled by linear mixed-effects regression analysis. During spontaneous breathing, ICA-BF was reduced from normovolemia (247, 202-284 mL/min) to hypovolemia (218, 194-271 mL/min). During combined PPV and hypovolemia, ICA-BF decreased by 15% (200, 152-231 mL/min, P = 0.001). Regression analysis attributed this fall to concurrent reductions in CI (β: 43.2, SE: 17.1, P = 0.013) and ETCO (β: 32.8, SE: 9.3, P = 0.001). Mean arterial pressure was maintained and did not contribute to ICA-BF variance. In healthy awake subjects, ICA-BF was significantly reduced during simulated hypovolemia combined with noninvasive PPV Reductions in CI and ETCO had additive effects on ICA-BF reduction. In hypovolemic patients, even low-pressure noninvasive ventilation may cause clinically relevant reductions in CBF, despite maintained arterial blood pressure.
Topics: Adult; Arterial Pressure; Blood Flow Velocity; Blood Pressure; Carotid Artery, Internal; Cerebrovascular Circulation; Female; Healthy Volunteers; Heart Rate; Hemodynamics; Humans; Hypocapnia; Hypovolemia; Hypoxia, Brain; Lower Body Negative Pressure; Male; Noninvasive Ventilation; Regional Blood Flow; Respiration, Artificial; Ultrasonography, Doppler
PubMed: 27702883
DOI: 10.14814/phy2.12969 -
Critical Care (London, England) Oct 2016For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and... (Review)
Review
For patients who survive the initial bleeding event of a ruptured brain aneurysm, delayed cerebral ischemia (DCI) is one of the most important causes of mortality and poor neurological outcome. New insights in the last decade have led to an important paradigm shift in the understanding of DCI pathogenesis. Large-vessel cerebral vasospasm has been challenged as the sole causal mechanism; new hypotheses now focus on the early brain injury, microcirculatory dysfunction, impaired autoregulation, and spreading depolarization. Prevention of DCI primarily relies on nimodipine administration and optimization of blood volume and cardiac performance. Neurological monitoring is essential for early DCI detection and intervention. Serial clinical examination combined with intermittent transcranial Doppler ultrasonography and CT angiography (with or without perfusion) is the most commonly used monitoring paradigm, and usually suffices in good grade patients. By contrast, poor grade patients (WFNS grades 4 and 5) require more advanced monitoring because stupor and coma reduce sensitivity to the effects of ischemia. Greater reliance on CT perfusion imaging, continuous electroencephalography, and invasive brain multimodality monitoring are potential strategies to improve situational awareness as it relates to detecting DCI. Pharmacologically-induced hypertension combined with volume is the established first-line therapy for DCI; a good clinical response with reversal of the presenting deficit occurs in 70 % of patients. Medically refractory DCI, defined as failure to respond adequately to these measures, should trigger step-wise escalation of rescue therapy. Level 1 rescue therapy consists of cardiac output optimization, hemoglobin optimization, and endovascular intervention, including angioplasty and intra-arterial vasodilator infusion. In highly refractory cases, level 2 rescue therapies are also considered, none of which have been validated. This review provides an overview of current state-of-the-art care for DCI management.
Topics: Brain Ischemia; Calcium Channel Blockers; Disease Management; Humans; Hyponatremia; Hypotension; Hypovolemia; Microcirculation; Nimodipine; Subarachnoid Hemorrhage; Time Factors; Tomography, X-Ray Computed; Ultrasonography, Doppler, Transcranial; Vasoconstrictor Agents; Vasospasm, Intracranial
PubMed: 27737684
DOI: 10.1186/s13054-016-1447-6 -
Der Anaesthesist Feb 2021Intravascular fluid administration belongs to the cornerstones of perioperative treatment with a substantial impact on surgical outcome especially with respect to major... (Review)
Review
Intravascular fluid administration belongs to the cornerstones of perioperative treatment with a substantial impact on surgical outcome especially with respect to major abdominal surgery. By avoidance of hypovolemia and hypervolemia, adequate perioperative fluid management significantly contributes to the reduction of insufficient tissue perfusion as a determinant of postoperative morbidity and mortality. The effective use of intravascular fluids requires detailed knowledge of the substances as well as measures to guide fluid therapy. Fluid management already starts preoperatively and should be continued in the postoperative setting (recovery room, peripheral ward) considering a patient-adjusted and surgery-adjusted hemodynamic monitoring. Communication between all team members participating in perioperative care is essential to optimize fluid management.
Topics: Abdomen; Fluid Therapy; Hemodynamic Monitoring; Humans; Hypovolemia; Perioperative Care
PubMed: 33034685
DOI: 10.1007/s00101-020-00867-7 -
Acta Gastro-enterologica Belgica 2019Low serum albumin is common in cirrhosis and is associated with a reduced survival. Moreover, in this setting, the native isoform of albumin can be severely reduced due... (Review)
Review
Low serum albumin is common in cirrhosis and is associated with a reduced survival. Moreover, in this setting, the native isoform of albumin can be severely reduced due to several posttranscriptional changes that impair the non-oncotic properties of the molecule. Due to its oncotic power, albumin acts as a powerful plasma expander. As such, it can antagonize the consequences of effective hypovolemia deriving from the systemic hemodynamics abnormalities that characterize advanced cirrhosis. Indeed, the current established indications to the use of albumin in this context pertain to conditions deriving from an acute drop of effective volemia. Recent advances have shown that the pathophysiological background of decompensated cirrhosis is characterized by a sustained systemic inflammatory and pro-oxidant state deriving by an abnormal bacterial translocation from the gut. These abnormalities ultimately lead to the multiorgan dysfunction. In this cascade of events, long-term albumin administration could act against several pathogenic factors through its non-oncotic properties, thus representing a potential multi-target mechanistic treatment. Over the last year, two randomized clinical trials on this topic were published. The ANSWER Trial demonstrated that the long-term albumin administration in patients with decompensated cirrhosis improves overall survival, reduces the incidence of complications and the need of hospitalizations and ameliorates the quality of life, being cost-effective. The MACHT trial challenged these results, but the differences between the two studies (sample size, baseline severity of cirrhosis, length of follow-up and amount of albumin administered) could explain its variant results, providing the basis for further insights into this matter.
Topics: Albumins; Fibrosis; Humans; Hypovolemia; Liver Cirrhosis; Quality of Life; Serum Albumin
PubMed: 31314192
DOI: No ID Found -
Physiological Reviews Jan 2019This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered... (Review)
Review
This review presents lower body negative pressure (LBNP) as a unique tool to investigate the physiology of integrated systemic compensatory responses to altered hemodynamic patterns during conditions of central hypovolemia in humans. An early review published in Physiological Reviews over 40 yr ago (Wolthuis et al. Physiol Rev 54: 566-595, 1974) focused on the use of LBNP as a tool to study effects of central hypovolemia, while more than a decade ago a review appeared that focused on LBNP as a model of hemorrhagic shock (Cooke et al. J Appl Physiol (1985) 96: 1249-1261, 2004). Since then there has been a great deal of new research that has applied LBNP to investigate complex physiological responses to a variety of challenges including orthostasis, hemorrhage, and other important stressors seen in humans such as microgravity encountered during spaceflight. The LBNP stimulus has provided novel insights into the physiology underlying areas such as intolerance to reduced central blood volume, sex differences concerning blood pressure regulation, autonomic dysfunctions, adaptations to exercise training, and effects of space flight. Furthermore, approaching cardiovascular assessment using prediction models for orthostatic capacity in healthy populations, derived from LBNP tolerance protocols, has provided important insights into the mechanisms of orthostatic hypotension and central hypovolemia, especially in some patient populations as well as in healthy subjects. This review also presents a concise discussion of mathematical modeling regarding compensatory responses induced by LBNP. Given the diverse applications of LBNP, it is to be expected that new and innovative applications of LBNP will be developed to explore the complex physiological mechanisms that underline health and disease.
Topics: Animals; Blood Pressure; Hemodynamics; Humans; Hypotension, Orthostatic; Hypovolemia; Lower Body Negative Pressure; Space Flight
PubMed: 30540225
DOI: 10.1152/physrev.00006.2018 -
Sensors (Basel, Switzerland) Feb 2022This paper presents a novel computational algorithm to estimate blood volume decompensation state based on machine learning (ML) analysis of multi-modal...
This paper presents a novel computational algorithm to estimate blood volume decompensation state based on machine learning (ML) analysis of multi-modal wearable-compatible physiological signals. To the best of our knowledge, our algorithm may be the first of its kind which can not only discriminate normovolemia from hypovolemia but also classify hypovolemia into absolute hypovolemia and relative hypovolemia. We realized our blood volume classification algorithm by (i) extracting a multitude of features from multi-modal physiological signals including the electrocardiogram (ECG), the seismocardiogram (SCG), the ballistocardiogram (BCG), and the photoplethysmogram (PPG), (ii) constructing two ML classifiers using the features, one to classify normovolemia vs. hypovolemia and the other to classify hypovolemia into absolute hypovolemia and relative hypovolemia, and (iii) sequentially integrating the two to enable multi-class classification (normovolemia, absolute hypovolemia, and relative hypovolemia). We developed the blood volume decompensation state classification algorithm using the experimental data collected from six animals undergoing normovolemia, relative hypovolemia, and absolute hypovolemia challenges. Leave-one-subject-out analysis showed that our classification algorithm achieved an F1 score and accuracy of (i) 0.93 and 0.89 in classifying normovolemia vs. hypovolemia, (ii) 0.88 and 0.89 in classifying hypovolemia into absolute hypovolemia and relative hypovolemia, and (iii) 0.77 and 0.81 in classifying the overall blood volume decompensation state. The analysis of the features embedded in the ML classifiers indicated that many features are physiologically plausible, and that multi-modal SCG-BCG fusion may play an important role in achieving good blood volume classification efficacy. Our work may complement existing computational algorithms to estimate blood volume compensatory reserve as a potential decision-support tool to provide guidance on context-sensitive hypovolemia therapeutic strategy.
Topics: Algorithms; Animals; Blood Volume; Hemorrhage; Hypovolemia; Machine Learning; Wearable Electronic Devices
PubMed: 35214238
DOI: 10.3390/s22041336 -
Journal of the American Association For... Sep 2022Balanced anesthesia-the use of a combination of drugs to achieve a desired anesthetic plane-offers many benefits, including smoother induction and recovery and fewer...
Balanced anesthesia-the use of a combination of drugs to achieve a desired anesthetic plane-offers many benefits, including smoother induction and recovery and fewer adverse effects than occur with individual drugs. Although premedication prior to inhalant anesthesia is routine in other species, mice are commonly induced with gas anesthesia alone. The hypothesis of this study was that premedication with ketamine or xylazine would safely reduce the stress of isoflurane induction and lower the minimum alveolar concentration (MAC) of isoflurane. Young adult male and female C57BL/6J mice were premedicated with ketamine (100 mg/kg), xylazine (4 mg/kg), or isotonic crystalloid (0.1 mL) and were used in 4 experiments. First, isoflurane induction was video recorded under all test conditions, and the videos were scored according to a behavioral ethogram to identify signs of distress. Mice in the ketamine group experienced tremors and ataxia before and dur- ing induction. Therefore, ketamine was given after induction with isoflurane in subsequent experiments. Second, the MAC value for each anesthetic protocol was determined by using quantal and bracketing analysis. Third, mice were anesthetized according to the 3 protocols, and vital parameters were monitored for 60 min. Finally, anesthetized mice were challenged with hypoxia and hypovolemia, and vital parameters were monitored. Premedication with xylazine significantly reduced the stress scores for isoflurane induction (control, 7.3 ± 1.5; ketamine, 6.0 ± 3.0; xylazine, 3.1 ± 1.0). Ketamine and xylazine both reduced the MAC of isoflurane (control, 1.89%; ketamine, 0.96%; xylazine, 1.20%). All mice survived 60 min of anesthesia and the hypoxia-hypovolemia challenge. Premedication with xylazine reduced the stress of induction and lowered the necessary dose of isoflurane in C57BL/6J mice to maintain a surgical plane of anesthesia. We recommend administering xylazine before isoflurane induction and anesthesia of healthy mice that are undergoing procedures in which 100% oxygen is provided and anticipated blood loss is less than 10% to 15% of the total blood volume.
Topics: Anesthetics, Inhalation; Animals; Balanced Anesthesia; Crystalloid Solutions; Female; Hypovolemia; Hypoxia; Isoflurane; Ketamine; Male; Mice; Mice, Inbred C57BL; Oxygen; Xylazine
PubMed: 35940848
DOI: 10.30802/AALAS-JAALAS-21-000125 -
Medical Sciences (Basel, Switzerland) Oct 2022SARS-CoV-2-infected symptomatic patients often suffer from high fever and loss of appetite which are responsible for the deficit of fluids and of protein intake. Many... (Review)
Review
SARS-CoV-2-infected symptomatic patients often suffer from high fever and loss of appetite which are responsible for the deficit of fluids and of protein intake. Many patients admitted to the emergency room are, therefore, hypovolemic and hypoproteinemic and often suffer from respiratory distress accompanied by ground glass opacities in the CT scan of the lungs. Ischemic damage in the lung capillaries is responsible for the microscopic hallmark, diffuse alveolar damage (DAD) characterized by hyaline membrane formation, fluid invasion of the alveoli, and progressive arrest of blood flow in the pulmonary vessels. The consequences are progressive congestion, increase in lung weight, and progressive hypoxia (progressive severity of ARDS). Sequestration of blood in the lungs worsens hypovolemia and ischemia in different organs. This is most probably responsible for the recruitment of inflammatory cells into the ischemic peripheral tissues, the release of acute-phase mediators, and for the persistence of elevated serum levels of positive acute-phase markers and of hypoalbuminemia. Autopsy studies have been performed mostly in patients who died in the ICU after SARS-CoV-2 infection because of progressive acute respiratory distress syndrome (ARDS). In the death certification charts, after respiratory insufficiency, hypovolemic heart failure should be mentioned as the main cause of death.
Topics: Humans; COVID-19; SARS-CoV-2; Hypovolemia; Respiratory Distress Syndrome; Lung
PubMed: 36278528
DOI: 10.3390/medsci10040058 -
American Journal of Kidney Diseases :... May 2023Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such... (Review)
Review
RATIONALE & OBJECTIVE
Sick day medication guidance (SDMG) involves withholding or adjusting specific medications in the setting of acute illnesses that could contribute to complications such as hypotension, acute kidney injury (AKI), or hypoglycemia. We sought to achieve consensus among clinical experts on recommendations for SDMG that could be studied in future intervention studies.
STUDY DESIGN
A modified Delphi process following guidelines for conducting and reporting Delphi studies.
SETTING & PARTICIPANTS
An international group of clinicians with expertise relevant to SDMG was recruited through purposive and snowball sampling. A scoping review of the literature was presented, followed by 3 sequential rounds of development, refinement, and voting on recommendations. Meetings were held virtually and structured to allow the participants to provide their input and rapidly prioritize and refine ideas.
OUTCOME
Opinions of participants were measured as the percentage who agreed with each recommendation, whereas consensus was defined as >75% agreement.
ANALYTICAL APPROACH
Quantitative data were summarized using counts and percentages. A qualitative content analysis was performed to capture the context of the discussion around recommendations and any additional considerations brought forward by participants.
RESULTS
The final panel included 26 clinician participants from 4 countries and 10 clinical disciplines. Participants reached a consensus on 42 specific recommendations: 5 regarding the signs and symptoms accompanying volume depletion that should trigger SDMG; 6 regarding signs that should prompt urgent contact with a health care provider (including a reduced level of consciousness, severe vomiting, low blood pressure, presence of ketones, tachycardia, and fever); and 14 related to scenarios and strategies for patient self-management (including frequent glucose monitoring, checking ketones, fluid intake, and consumption of food to prevent hypoglycemia). There was consensus that renin-angiotensin system inhibitors, diuretics, nonsteroidal anti-inflammatory drugs, sodium/glucose cotransporter 2 inhibitors, and metformin should be temporarily stopped. Participants recommended that insulin, sulfonylureas, and meglitinides be held only if blood glucose was low and that basal and bolus insulin be increased by 10%-20% if blood glucose was elevated. There was consensus on 6 recommendations related to the resumption of medications within 24-48 hours of the resolution of symptoms and the presence of normal patterns of eating and drinking.
LIMITATIONS
Participants were from high-income countries, predominantly Canada. Findings may not be generalizable to implementation in other settings.
CONCLUSIONS
A multidisciplinary panel of clinicians reached a consensus on recommendations for SDMG in the presence of signs and symptoms of volume depletion, as well as self-management strategies and medication instructions in this setting. These recommendations may inform the design of future trials of SDMG strategies.
Topics: Humans; Cardiovascular Diseases; Blood Glucose; Consensus; Blood Glucose Self-Monitoring; Sick Leave; Diabetes Mellitus; Hypoglycemia; Hypovolemia; Kidney; Insulins; Delphi Technique
PubMed: 36470530
DOI: 10.1053/j.ajkd.2022.10.012 -
European Journal of Heart Failure Jul 2023Patients recently hospitalized for heart failure (HF) often have unstable haemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF... (Randomized Controlled Trial)
Randomized Controlled Trial
Renal and blood pressure effects of dapagliflozin in recently hospitalized patients with heart failure with mildly reduced or preserved ejection fraction: Insights from the DELIVER trial.
AIMS
Patients recently hospitalized for heart failure (HF) often have unstable haemodynamics and experience worsening renal failure, and are at elevated risk for recurrent HF events. In DELIVER, dapagliflozin reduced HF events or cardiovascular death including among patients who were hospitalized or recently hospitalized.
METHODS AND RESULTS
We examined the effects of dapagliflozin versus placebo on estimated glomerular filtration rate (eGFR) slope (acute and chronic), 1-month change in systolic blood pressure, and the occurrence of serious hypovolaemic or renal adverse events in patients with and without HF hospitalization within 30 days of randomization. The 654 (90 randomized during hospitalization, 147 1-7 days post-discharge and 417 8-30 days post-discharge) recently hospitalized patients had lower baseline eGFR compared with those without recent HF hospitalization (median [interquartile range] 55 [43, 71] vs. 60 [47, 75] ml/min/1.73 m ). Dapagliflozin consistently reduced the risk of all-cause (p = 0.20), cardiac-related (p = 0.75), and HF-specific (p = 0.90) hospitalizations, irrespective of recent HF hospitalization. In those recently hospitalized, acute placebo-corrected eGFR reductions with dapagliflozin were modest and similar to patients without recent hospitalization (-2.0 [-4.1, +0.1] vs. -3.4 [-3.9, -2.9] ml/min/1.73 m , p = 0.12). Dapagliflozin's effect to slow chronic eGFR decline was similar regardless of recent hospitalization (p = 0.57). Dapagliflozin had a minimal effect on 1-month systolic blood pressure and to a similar degree in patients with and without recent hospitalization (-1.3 vs.-1.8 mmHg, p = 0.64). There was no treatment-related excess in renal or hypovolaemic serious adverse events, irrespective of recent HF hospitalization.
CONCLUSION
In patients recently hospitalized with HF, initiation of dapagliflozin had minimal effects on blood pressure and did not increase renal or hypovolaemic serious adverse events, yet afforded long-term cardiovascular and kidney protective effects. These data suggest that the benefit to risk ratio favours initiation of dapagliflozin among stabilized patients hospitalized or recently hospitalized for HF.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov NCT03619213.
Topics: Humans; Aftercare; Blood Pressure; Heart Failure; Hypovolemia; Kidney; Patient Discharge; Stroke Volume
PubMed: 37212168
DOI: 10.1002/ejhf.2915