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Critical Care (London, England) Feb 2024Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract... (Review)
Review
Septic shock typically requires the administration of vasopressors. Adrenergic agents remain the first choice, namely norepinephrine. However, their use to counteract life-threatening hypotension comes with potential adverse effects, so that non-adrenergic vasopressors may also be considered. The use of agents that act through different mechanisms may also provide an advantage. Nitric oxide (NO) is the main driver of the vasodilation that leads to hypotension in septic shock, so several agents have been tested to counteract its effects. The use of non-selective NO synthase inhibitors has been of questionable benefit. Methylene blue, an inhibitor of soluble guanylate cyclase, an important enzyme involved in the NO signaling pathway in the vascular smooth muscle cell, has also been proposed. However, more than 25 years since the first clinical evaluation of MB administration in septic shock, the safety and benefits of its use are still not fully established, and it should not be used routinely in clinical practice until further evidence of its efficacy is available.
Topics: Humans; Methylene Blue; Shock, Septic; Hypotension; Soluble Guanylyl Cyclase; Norepinephrine; Vasoconstrictor Agents
PubMed: 38365828
DOI: 10.1186/s13054-024-04839-w -
Neuropharmacology Sep 2024Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects,... (Review)
Review
Water is critical for survival and thirst is a powerful way of ensuring that fluid levels remain in balance. Overconsumption, however, can have deleterious effects, therefore optimization requires a need to balance the drive for water with the satiation of that water drive. This review will highlight our current understanding of how thirst is both generated and quenched, with particular focus on the roles of angiotensin II, glucagon like-peptide 1, and estradiol in turning on and off the thirst drive. Our understanding of the roles these bioregulators play has benefited from modern behavioral analyses, which have improved the time resolution of intake measures, allowing for attention to the details of the patterns within a bout of intake. This has led to behavioral interpretation in ways that are helpful in understanding the many controls of water intake and has expanded our understanding beyond the dichotomy that something which increases water intake is simply a "stimulator" while something that decreases water intake is simply a "satiety" factor. Synthesizing the available information, we describe a framework in which thirst is driven directly by perturbations in fluid intake and indirectly modified by several bioregulators. This allows us to better highlight areas that are in need of additional attention to form a more comprehensive understanding of how the system transitions between states of thirst and satiety.
Topics: Thirst; Humans; Animals; Drinking; Glucagon-Like Peptide 1; Angiotensin II; Estradiol; Satiation
PubMed: 38823577
DOI: 10.1016/j.neuropharm.2024.110009 -
Pharmacotherapy Aug 2023Significant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating... (Observational Study)
Observational Study
STUDY OBJECTIVE
Significant practice variation exists when selecting between hydrocortisone and vasopressin as second line agents in patients with septic shock in need of escalating doses of norepinephrine. The goal of this study was to assess differences in clinical outcomes between these two agents.
DESIGN
Multicenter, retrospective, observational study.
SETTING
Ten Ascension Health hospitals.
PATIENTS
Adult patients with presumed septic shock receiving norepinephrine prior to study drug initiation between December 2015 and August 2021.
INTERVENTION
Vasopressin (0.03-0.04 units/min) or hydrocortisone (200-300 mg/day).
MEASUREMENTS AND MAIN RESULTS
A total of 768 patients were included with a median (interquartile range) SOFA score of 10 (8-13), norepinephrine dose of 0.3 mcg/kg/min (0.1-0.5 mcg/kg/min), and lactate of 3.8 mmol/L (2.4-7.0 mmol/L) at initiation of the study drug. A significant difference in 28-day mortality was noted favoring hydrocortisone as an adjunct to norepinephrine after controlling for potential confounding factors (OR 0.46 [95% CI, 0.32-0.66]); similar results were seen following propensity score matching. Compared to vasopressin, hydrocortisone initiation was also associated with a higher rate of hemodynamic responsiveness (91.9% vs. 68.2%, p < 0.01), improved resolution of shock (68.8% vs. 31.5%, p < 0.01), and reduced recurrence of shock within 72 h (8.7% vs. 20.7%, p < 0.01).
CONCLUSIONS
Addition of hydrocortisone to norepinephrine was associated with a lower 28-day mortality in patients with septic shock, compared to the addition of vasopressin.
Topics: Humans; Adult; Norepinephrine; Hydrocortisone; Vasoconstrictor Agents; Retrospective Studies; Shock, Septic; Vasopressins
PubMed: 37148191
DOI: 10.1002/phar.2811 -
Ugeskrift For Laeger Apr 2024Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose...
Perioperative anaphylaxis is rare and the diagnosis is difficult to distinguish from normal side effects from anaesthesia. Anaesthetists should be able to diagnose anaphylaxis and treat promptly with adrenaline and fluids. Allergy investigation should be performed subsequently. This is a case report of perioperative anaphylaxis to propofol. Propofol contains refined soya oil and egg lecithin, but no connection between allergy to soy, egg or peanut and allergy to propofol has been proven, and international guidelines recommend that propofol can be used in patients with these food allergies.
Topics: Humans; Anaphylaxis; Propofol; Anesthetics, Intravenous; Drug Hypersensitivity; Female; Epinephrine; Male
PubMed: 38704709
DOI: 10.61409/V11230746 -
Allergy Jul 2023
Topics: Humans; Epinephrine
PubMed: 37171268
DOI: 10.1111/all.15767 -
Immunology and Allergy Clinics of North... Aug 2023After treating the acute anaphylactic reaction, the clinician's next task is to prevent a recurrence. The patient should be observed in the ED. How long this observation... (Review)
Review
After treating the acute anaphylactic reaction, the clinician's next task is to prevent a recurrence. The patient should be observed in the ED. How long this observation period should last depends on their clinical course, risk factors, and social support. All patients should be discharged with a prescription for 2 epinephrine autoinjectors and counseled on appropriate use. The patient should also receive education on the signs and symptoms of anaphylaxis and avoiding triggers. The patient should follow-up with an allergy specialist who can confirm triggers and provide immunotherapy as indicated.
Topics: Humans; Anaphylaxis; Epinephrine; Emergency Service, Hospital; Risk Factors
PubMed: 37394253
DOI: 10.1016/j.iac.2022.10.008 -
The New England Journal of Medicine Nov 2023
Topics: Humans; Arginine; Arginine Vasopressin; Diabetes Insipidus, Neurogenic
PubMed: 37966292
DOI: 10.1056/NEJMe2311293 -
Current Opinion in Gastroenterology May 2024The definition and diagnostic criteria of hepatorenal syndrome-acute kidney injury (HRS-AKI) has undergone recent changes. A major vasoconstrictor, terlipressin, has... (Review)
Review
PURPOSE OF REVIEW
The definition and diagnostic criteria of hepatorenal syndrome-acute kidney injury (HRS-AKI) has undergone recent changes. A major vasoconstrictor, terlipressin, has recently been approved as pharmacotherapy for HRS-AKI in the United States. The purpose of this review is to familiarize the readers with these new diagnostic criteria of HRS-AKI, and how best to use terlipressin.
RECENT FINDINGS
Terlipressin is effective either as bolus dosing or continuous infusion and can achieve reversal of HRS-AKI in approximately 40% of patients. Continuous infusion allows lower daily dose with equal efficacy and less side effects but not an approved mode of administration in the United States. Response to terlipressin in the randomized controlled trials was defined as repeat reduction of serum creatinine to less than 1.5 mg/dl. Newer studies will likely require response to treatment to be defined as a repeat serum creatinine to be less than 0.3 mg/dl from baseline. Terlipressin use is associated with ischemic side effects and potential for respiratory failure development.
SUMMARY
Careful patient selection and close monitoring are necessary for its use. Response to terlipressin with HRS-AKI reversal is associated with improved outcomes with better survival and less requirement for renal replacement therapy.
Topics: Humans; Terlipressin; Lypressin; Hepatorenal Syndrome; Creatinine; Treatment Outcome; Vasoconstrictor Agents; Acute Kidney Injury
PubMed: 38353275
DOI: 10.1097/MOG.0000000000001016 -
Critical Care Nursing QuarterlyCardiogenic shock (CS) is a complex and dreadful condition for which effective treatments remain unclear. The concerningly high mortality rate of CS emphasizes a need... (Review)
Review
Cardiogenic shock (CS) is a complex and dreadful condition for which effective treatments remain unclear. The concerningly high mortality rate of CS emphasizes a need for developing effective therapies to reduce its mortality and reverse its detrimental course. This article aims to provide an updated and evidence-based review of the pathophysiology of CS and the related pharmacotherapeutics with a special focus on vasoactive and inotropic agents.
Topics: Humans; Shock, Cardiogenic; Cardiotonic Agents; Vasoconstrictor Agents
PubMed: 38860953
DOI: 10.1097/CNQ.0000000000000513 -
International Journal of Molecular... Dec 2023Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the... (Review)
Review
Hepatorenal syndrome (HRS) is a disorder associated with cirrhosis and renal impairment, with portal hypertension as its major underlying cause. Moreover, HRS is the third most common cause of acute kidney injury, thus creating a major public health concern. This review summarizes the available information on the pathophysiological implications of HRS. We discuss pathogenesis associated with HRS. Mechanisms such as dysfunction of the circulatory system, bacterial infection, inflammation, impaired renal autoregulation, circulatory, and others, which have been identified as critical pathways for development of HRS, have become easier to diagnose in recent years. Additionally, relatively recently, renal dysfunction biomarkers have been found indicating renal injury, which are involved in the pathophysiology of HRS. This review also summarizes the available information on the management of HRS, focusing on vasoconstrictive drugs, renal replacement therapy, and liver transplant together with currently being investigated novel therapies. Analyzing new discoveries for the underlying causes of this condition assists the general research to improve understanding of the mechanism of pathophysiology and thus prevention of HRS.
Topics: Humans; Hepatorenal Syndrome; Kidney; Liver Cirrhosis; Liver Transplantation; Acute Kidney Injury; Vasoconstrictor Agents
PubMed: 38139297
DOI: 10.3390/ijms242417469