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Minerva Anestesiologica May 2020Norepinephrine is the first line vasopressor used in patients with septic shock. However, norepinephrine doses above 1 µg/kg/min are associated with mortality rates of... (Review)
Review
Norepinephrine is the first line vasopressor used in patients with septic shock. However, norepinephrine doses above 1 µg/kg/min are associated with mortality rates of over 80%, suggesting a need to implement adjunctive strategies prior to reaching this dosage. The present study therefore sought to review the existing and emergent vasopressor agents for patients with refractory septic shock. This paper summarizes the use of vasoactive drugs that may be considered in the context of refractory shock. The clinical application of present and future therapies and the related outcome are discussed. A review of the available literature indicated that vasopressin may be a good first option in patients with refractory septic shock, but evidence remains somewhat sparse. Although the use of vasopressin in these circumstances is likely preferable to the use of terlipressin, a pro-drug with an extended half-life, the use of selepressin, a pure V1 agonist, should be further assessed in future studies. Angiotensin II is another emerging option that uses a different signaling pathway. However, nitric oxide synthase inhibitors and methylene blue do not appear to be appropriate in the management of patients with refractory septic shock. In conclusion, the use of different adjunctive agents in combination with the use of norepinephrine may be useful in patients with refractory septic shock, but care must be taken to avoid excessive vasoconstriction.
Topics: Humans; Norepinephrine; Shock, Septic; Terlipressin; Vasoconstrictor Agents; Vasopressins
PubMed: 31994366
DOI: 10.23736/S0375-9393.20.13826-4 -
Chest Oct 2020Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg raise) to guide resuscitation and improve patient outcome.
RESEARCH QUESTION
Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?
STUDY DESIGN AND METHODS
We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first.
RESULTS
In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals.
INTERPRETATION
Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.
CLINICAL TRIAL REGISTRATION
NCT02837731.
Topics: Aged; Combined Modality Therapy; Female; Fluid Therapy; Humans; Hypotension; Male; Middle Aged; Prospective Studies; Resuscitation; Sepsis; Shock, Septic; Treatment Outcome; Vasoconstrictor Agents
PubMed: 32353418
DOI: 10.1016/j.chest.2020.04.025 -
The Western Journal of Emergency... Feb 2021Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Most experts recommend norepinephrine as the first-line agent in septic shock. Our objective was to determine the effectiveness and safety of norepinephrine in patients with septic shock.
METHODS
We searched the Cochrane Central Register of Controlled Trials and Epistemonikos, as well as MEDLINE from 1966 till August 2019. Screening of full texts, evaluation for eligibility, and data extraction were done by four independent reviewers. We estimated risk ratios (RR) and mean differences (MD) using a random-effects model with 95% confidence intervals (CI). The primary outcomes included the number of participants who achieved the target mean arterial pressure (MAP), time to achieve the target MAP, and number of participants with all-cause 28-day mortality. The secondary outcomes included the length of stay in the intensive care unit, length of hospital stay, incidence of arrhythmia and myocardial infarction, vasopressor-free days, and number of participants with all-cause 90-day mortality.
RESULTS
We identified 11 randomized controlled trials with a total of 4,803 participants. There was no difference in the number of participants who achieved the target MAP between those patients receiving norepinephrine and other vasopressors (RR 1.44; 95% CI, 0.32 to 6.54; P = 0.640; I = 94%; two trials, 116 participants). There was no significant difference in time to achieve the target MAP (MD -0.05; 95%, CI, -0.32 to 0.21; P = 0.690; I = 26%; two trials, 1763 participants) and all-cause 28-day mortality (RR 0.95; 95% CI, 0.89 to 1.02; P = 0.160; I = 0%; seven trials, 4,139 participants). Regarding the secondary outcome, norepinephrine may significantly reduce the incidence of arrhythmia as compared to other vasopressors (RR 0.64; 95% CI, 0.42 to 0.97; P = 0.030; I = 64%; six trials, 3974 participants). There was no difference in the incidence of myocardial infarction (RR 1.28; 95% CI, 0.79 to 2.09), vasopressor-free day (RR 0.46; 95% CI, -1.82 to 2.74) and all-cause 90-day mortality (RR 1.08; 95% CI, 0.96 to 1.21) between norepinephrine and vasopressors.
CONCLUSION
In minimizing the occurrence of an arrhythmia, norepinephrine is superior to other vasopressors, making it safe to be used in septic shock. However, there was insufficient evidence concerning mortality and achievement of the target MAP outcomes.
Topics: Humans; Intensive Care Units; Length of Stay; Norepinephrine; Shock, Septic; Vasoconstrictor Agents
PubMed: 33856300
DOI: 10.5811/westjem.2020.10.47825 -
Intensive Care Medicine Oct 2020ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine,... (Randomized Controlled Trial)
Randomized Controlled Trial
Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.
PURPOSE
ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.
METHODS
In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.
RESULTS
Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).
CONCLUSION
Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.
Topics: Adult; Australia; Humans; Hypotension; Intensive Care Units; Midodrine; Vasoconstrictor Agents
PubMed: 32885276
DOI: 10.1007/s00134-020-06216-x -
Critical Care (London, England) Mar 2022This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at... (Review)
Review
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2022. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2022 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from https://link.springer.com/bookseries/8901 .
Topics: Critical Care; Humans; Hypotension; Shock; Vasoconstrictor Agents
PubMed: 35337346
DOI: 10.1186/s13054-022-03911-7 -
Clinical and Molecular Hepatology Oct 2023Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis,... (Review)
Review
Hepatorenal syndrome (HRS), a progressive but potentially reversible deterioration of kidney function, remains a major complication in patients with advanced cirrhosis, often leading to death before liver transplantation (LT). Recent updates in the pathophysiology, definition, and classification of HRS have led to a complete revision of the nomenclature and diagnostic criteria for HRS type 1, which was renamed HRS-acute kidney injury (AKI). HRS is characterized by severe impairment of kidney function due to increased splanchnic blood flow, activation of several vasoconstriction factors, severe vasoconstriction of the renal arteries in the absence of kidney histologic abnormalities, nitric oxide dysfunction, and systemic inflammation. Diagnosis of HRS remains a challenge because of the lack of specific diagnostic biomarkers that accurately distinguishes structural from functional AKI, and mainly involves the differential diagnosis from other forms of AKI, particularly acute tubular necrosis. The optimal treatment of HRS is LT. While awaiting LT, treatment options include vasoconstrictor drugs to counteract splanchnic arterial vasodilation and plasma volume expansion by intravenous albumin infusion. In patients with HRS unresponsive to pharmacological treatment and with conventional indications for kidney replacement therapy (KRT), such as volume overload, uremia, or electrolyte imbalances, KRT may be applied as a bridging therapy to transplantation. Other interventions, such as transjugular intrahepatic portosystemic shunt, and artificial liver support systems have a very limited role in improving outcomes in HRS. Although recently developed novel therapies have potential to improve outcomes of patients with HRS, further studies are warranted to validate the efficacy of these novel agents.
Topics: Humans; Hepatorenal Syndrome; Liver Cirrhosis; Liver Transplantation; Vasoconstrictor Agents; Acute Kidney Injury
PubMed: 37050843
DOI: 10.3350/cmh.2023.0024 -
Drug Design, Development and Therapy 2019This review discusses historical and recent pharmacological and clinical data on the anti-edematous, anti-inflammatory, and venotonic properties of escin (Reparil).... (Review)
Review
This review discusses historical and recent pharmacological and clinical data on the anti-edematous, anti-inflammatory, and venotonic properties of escin (Reparil). Escin, the active component of , or horse chestnut, is available as orally absorbable dragées and as a transdermal gel. The anti-inflammatory and anti-edematous effects of escin have been studied over many years in pre-clinical models. More recent data confirm the anti-inflammatory properties of escin in reducing vascular permeability in inflamed tissues, thereby inhibiting edema formation. The venotonic effects of escin have been demonstrated primarily by in vitro studies of isolated human saphenous veins. The ability of escin to prevent hypoxia-induced disruption to the normal expression and distribution of platelet endothelial cell-adhesion molecule-1 may help explain its protective effect on blood vessel permeability. Escin oral dragées and transdermal gel have both demonstrated efficacy in blunt trauma injuries and in chronic venous insufficiency. Both oral escin and the transdermal gel are well tolerated.
Topics: Animals; Anti-Inflammatory Agents; Edema; Escin; Humans; Inflammation; Saphenous Vein; Vasoconstrictor Agents
PubMed: 31631970
DOI: 10.2147/DDDT.S207720 -
Clinical Journal of the American... Nov 2022AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal...
AKI is commonly encountered in patients with decompensated cirrhosis, and it is associated with unfavorable outcomes. Among factors specific to cirrhosis, hepatorenal syndrome type 1, also referred to as hepatorenal syndrome-AKI, is the most salient and unique etiology. Patients with cirrhosis are vulnerable to traditional causes of AKI, such as prerenal azotemia, acute tubular injury, and acute interstitial nephritis. In addition, other less common etiologies of AKI specifically related to chronic liver disease should be considered, including abdominal compartment syndrome, cardiorenal processes linked to cirrhotic cardiomyopathy and portopulmonary hypertension, and cholemic nephropathy. Furthermore, certain types of GN can cause AKI in cirrhosis, such as IgA nephropathy or viral hepatitis related. Therefore, a comprehensive diagnostic approach is needed to evaluate patients with cirrhosis presenting with AKI. Management should be tailored to the specific underlying etiology. Albumin-based volume resuscitation is recommended in prerenal AKI. Acute tubular injury and acute interstitial nephritis are managed with supportive care, withdrawal of the offending agent, and, potentially, corticosteroids in acute interstitial nephritis. Short of liver transplantation, vasoconstrictor therapy is the primary treatment for hepatorenal syndrome type 1. Timing of initiation of vasoconstrictors, the rise in mean arterial pressure, and the degree of cholestasis are among the factors that determine vasoconstrictor responsiveness. Large-volume paracentesis and diuretics are indicated to relieve intra-abdominal hypertension and renal vein congestion. Direct-acting antivirals with or without immunosuppression are used to treat hepatitis B/C-associated GN. In summary, AKI in cirrhosis requires careful consideration of multiple potentially pathogenic factors and the implementation of targeted therapeutic interventions.
Topics: Humans; Hepatorenal Syndrome; Antiviral Agents; Biomarkers; Hepatitis C, Chronic; Acute Kidney Injury; Liver Cirrhosis; Vasoconstrictor Agents; Nephritis, Interstitial
PubMed: 35902128
DOI: 10.2215/CJN.03040322 -
International Journal of Molecular... Feb 2023During hemorrhagic shock, blood loss causes a fall in blood pressure, decreases cardiac output, and, consequently, O transport. The current guidelines recommend the... (Review)
Review
During hemorrhagic shock, blood loss causes a fall in blood pressure, decreases cardiac output, and, consequently, O transport. The current guidelines recommend the administration of vasopressors in addition to fluids to maintain arterial pressure when life-threatening hypotension occurs in order to prevent the risk of organ failure, especially acute kidney injury. However, different vasopressors exert variable effects on the kidney, depending on the nature and dose of the substance chosen as follows: Norepinephrine increases mean arterial pressure both via its α-1-mediated vasoconstriction leading to increased systemic vascular resistance and its β1-related increase in cardiac output. Vasopressin, through activation of V1-a receptors, induces vasoconstriction, thus increasing mean arterial pressure. In addition, these vasopressors have the following different effects on renal hemodynamics: Norepinephrine constricts both the afferent and efferent arterioles, whereas vasopressin exerts its vasoconstrictor properties mainly on the efferent arteriole. Therefore, this narrative review discusses the current knowledge of the renal hemodynamic effects of norepinephrine and vasopressin during hemorrhagic shock.
Topics: Humans; Norepinephrine; Shock, Hemorrhagic; Shock, Septic; Hemodynamics; Vasopressins; Vasoconstrictor Agents; Kidney
PubMed: 36835514
DOI: 10.3390/ijms24044103 -
Journal of Intensive Care Medicine Sep 2021Preexisting heart failure (HF) in patients with sepsis is associated with worse clinical outcomes. Core sepsis management includes aggressive volume resuscitation... (Review)
Review
Preexisting heart failure (HF) in patients with sepsis is associated with worse clinical outcomes. Core sepsis management includes aggressive volume resuscitation followed by vasopressors (and potentially inotropes) if fluid is inadequate to restore perfusion; however, large fluid boluses and vasoactive agents are concerning amid the cardiac dysfunction of HF. This review summarizes evidence regarding the influence of HF on sepsis clinical outcomes, pathophysiologic concerns, resuscitation targets, hemodynamic interventions, and adjunct management (ie, antiarrhythmics, positive pressure ventilatory support, and renal replacement therapy) in patients with sepsis and preexisting HF. Patients with sepsis and preexisting HF receive less fluid during resuscitation; however, evidence suggests traditional fluid resuscitation targets do not increase the risk of adverse events in HF patients with sepsis and likely improve outcomes. Norepinephrine remains the most well-supported vasopressor for patients with sepsis with preexisting HF, while dopamine may induce more cardiac adverse events. Dobutamine should be used cautiously given its generally detrimental effects but may have an application when combined with norepinephrine in patients with low cardiac output. Management of chronic HF medications warrants careful consideration for continuation or discontinuation upon development of sepsis, and β-blockers may be appropriate to continue in the absence of acute hemodynamic decompensation. Optimal management of atrial fibrillation may include β-blockers after acute hemodynamic stabilization as they have also shown independent benefits in sepsis. Positive pressure ventilatory support and renal replacement must be carefully monitored for effects on cardiac function when HF is present.
Topics: Fluid Therapy; Heart Failure; Humans; Resuscitation; Sepsis; Shock, Septic; Vasoconstrictor Agents
PubMed: 32495686
DOI: 10.1177/0885066620928299