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The American Journal of Emergency... Jul 2023Septic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35-40%. Vasopressin (AVP) is a second-line vasoactive agent...
BACKGROUND
Septic shock is a leading cause of death in intensive care units (ICUs), with short-term mortality rates of 35-40%. Vasopressin (AVP) is a second-line vasoactive agent for septic shock, and recent studies suggest that early AVP use can be beneficial. However, differences between early initiation of AVP combined with norepinephrine (NE) and nonearly AVP with NE are unclear. A retrospective cohort research was designed to explore the effects of early AVP initiation versus nonearly AVP initiation.
METHODS
This retrospective single-center cohort study included adult patients with septic shock from the MIMIC (Medical Information Mart for Intensive Care)-IV database. According to whether AVP was used early in the ICU (intensive care unit), patients were assigned to the early- (within 6 h of septic shock onset) and non-early-AVP (at least 6 h after septic shock onset) groups. The primary outcome was 28-day mortality. The secondary outcomes were ICU and hospital mortality, the numbers of vasopressor-free and ventilation-free days at 28 days, ICU length of stay (LOS), hospital LOS, sequential organ failure assessment (SOFA) score on days 2 and 3, and renal replacement therapy (RRT) use on days 2 and 3. Univariate and multivariate cox proportional-hazards regression, propensity-score matching were used to analyze the differences between the groups.
RESULTS
The study included 531 patients with septic shock: 331 (62.5%) in the early-AVP group and 200 (37.5%) in the non-early-AVP group. For 1:1 matching, 158 patients in the early-AVP group were matched with the same number of patients with nonearly AVP. Regarding the primary outcome, there was no significant difference between the early- and non-early-AVP groups in 28-day mortality (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.68-1.24). For the secondary outcomes, there were no differences between the early- and non-early-AVP groups in ICU mortality (HR = 0.95, 95% CI = 0.67-1.35), hospital mortality (HR = 0.95, 95% CI = 0.69-1.31), the numbers of vasopressor-free and ventilation-free days at 28 days, ICU LOS, hospital LOS, SOFA score on days 2 and 3, and RRT use on days 2 and 3.
CONCLUSIONS
There was no difference in short-term mortality between early AVP combined with NE and nonearly AVP with NE in septic shock.
Topics: Adult; Humans; Norepinephrine; Retrospective Studies; Shock, Septic; Cohort Studies; Vasopressins; Vasoconstrictor Agents; Intensive Care Units
PubMed: 37167890
DOI: 10.1016/j.ajem.2023.04.040 -
Critical Care Medicine Aug 2023To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and...
OBJECTIVES
To investigate the effects of immediate start of norepinephrine versus initial fluid loading followed by norepinephrine on macro hemodynamics, regional splanchnic and intestinal microcirculatory flows in endotoxic shock.
DESIGN
Animal experimental study.
SETTING
University translational research laboratory.
SUBJECTS
Fifteen Landrace pigs.
INTERVENTIONS
Shock was induced by escalating dose of lipopolysaccharide. Animals were allocated to immediate start of norepinephrine (i-NE) ( n = 6) versus mandatory 1-hour fluid loading (30 mL/kg) followed by norepinephrine (i-FL) ( n = 6). Once mean arterial pressure greater than or equal to 75 mm Hg was, respectively, achieved, successive mini-fluid boluses of 4 mL/kg of Ringer Lactate were given whenever: a) arterial lactate greater than 2.0 mmol/L or decrease less than 10% per 30 min and b) fluid responsiveness was judged to be positive. Three additional animals were used as controls (Sham) ( n = 3). Time × group interactions were evaluated by repeated-measures analysis of variance.
MEASUREMENTS AND MAIN RESULTS
Hypotension was significantly shorter in i-NE group (7.5 min [5.5-22.0 min] vs 49.3 min [29.5-60.0 min]; p < 0.001). Regional mesenteric and microcirculatory flows at jejunal mucosa and serosa were significantly higher in i-NE group at 4 and 6 hours after initiation of therapy ( p = 0.011, p = 0.032, and p = 0.017, respectively). Misdistribution of intestinal microcirculatory blood flow at the onset of shock was significantly reversed in i-NE group ( p < 0.001), which agreed with dynamic changes in mesenteric-lactate levels ( p = 0.01) and venous-to-arterial carbon dioxide differences ( p = 0.001). Animals allocated to i-NE showed significantly higher global end-diastolic volumes ( p = 0.015) and required significantly less resuscitation fluids ( p < 0.001) and lower doses of norepinephrine ( p = 0.001) at the end of the experiment. Pulmonary vascular permeability and extravascular lung water indexes were significantly lower in i-NE group ( p = 0.021 and p = 0.004, respectively).
CONCLUSIONS
In endotoxemic shock, immediate start of norepinephrine significantly improved regional splanchnic and intestinal microcirculatory flows when compared with mandatory fixed-dose fluid loading preceding norepinephrine. Immediate norepinephrine strategy was related with less resuscitation fluids and lower vasopressor doses at the end of the experiment.
Topics: Animals; Swine; Norepinephrine; Microcirculation; Splanchnic Circulation; Vasoconstrictor Agents; Shock, Septic; Hemodynamics; Lactates
PubMed: 37255347
DOI: 10.1097/CCM.0000000000005885 -
Critical Care Medicine Dec 2023To determine if angiotensin II is associated with improved outcomes as measured by 30- and 90-day mortality as well as other secondary outcomes such as organ dysfunction...
OBJECTIVES
To determine if angiotensin II is associated with improved outcomes as measured by 30- and 90-day mortality as well as other secondary outcomes such as organ dysfunction and adverse events.
DESIGN
Retrospective, matched analysis of patients receiving angiotensin II compared with both historical and concurrent controls receiving equivalent doses of nonangiotensin II vasopressors.
SETTING
Multiple ICUs in a large, university-based hospital.
PATIENTS
Eight hundred thirteen adult patients with shock admitted to an ICU and requiring vasopressor support.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
Angiotensin II use had no association with the primary outcome of 30-day mortality (60% vs 56%; p = 0.292). The secondary outcome of 90-day mortality was also similar (65% vs 63%; p = 0.440) as were changes in Sequential Organ Failure Assessment scores over a 5-day monitoring period after enrollment. Angiotensin II was not associated with increased rates of kidney replacement therapy (odds ratio [OR], 1.39; 95% CI, 0.88-2.19; p = 0.158) or receipt of mechanical ventilation (OR, 1.50; 95% CI, 0.41-5.51; p = 0.539) after enrollment, and the rate of thrombotic events was similar between angiotensin II and control patients (OR, 1.02; 95% CI, 0.71-1.48; p = 0.912).
CONCLUSIONS
In patients with severe shock, angiotensin II was not associated with improved mortality or organ dysfunction and was not associated with an increased rate of adverse events.
Topics: Adult; Humans; Angiotensin II; Multiple Organ Failure; Retrospective Studies; Shock; Vasoconstrictor Agents
PubMed: 37378469
DOI: 10.1097/CCM.0000000000005975 -
Experimental Eye Research Aug 2023Adrenaline is a sympathomimetic drug used to maintain pupil dilation and to decrease the risk of bleeding. The aim of this study was to demonstrate if adrenaline could...
Adrenaline is a sympathomimetic drug used to maintain pupil dilation and to decrease the risk of bleeding. The aim of this study was to demonstrate if adrenaline could exert antifibrotic effects in glaucoma surgery. Adrenaline was tested in fibroblast-populated collagen contraction assays and there was a dose-response decrease in fibroblast contractility: matrices decreased to 47.4% (P = 0.0002) and 86.6% (P = 0.0036) with adrenaline 0.0005% and 0.01%, respectively. There was no significant decrease in cell viability even at high concentrations. Human Tenon's fibroblasts were also treated with adrenaline (0%, 0.0005%, 0.01%) for 24 h and RNA-Sequencing was performed on the Illumina NextSeq 2000. We carried out detailed gene ontology, pathway, disease and drug enrichment analyses. Adrenaline 0.01% upregulated 26 G1/S and 11 S-phase genes, and downregulated 23 G2 and 17 M-phase genes (P < 0.05). Adrenaline demonstrated similar pathway enrichment to mitosis and spindle checkpoint regulation. Adrenaline 0.05% was also injected subconjunctivally during trabeculectomy, PreserFlo Microshunt and Baerveldt 350 tube surgeries, and patients did not experience any adverse effects. Adrenaline is a safe and cheap antifibrotic drug that significantly blocks key cell cycle genes when used at high concentrations. Unless contraindicated, we recommend subconjunctival injections of adrenaline (0.05%) in all glaucoma bleb-forming surgeries.
Topics: Humans; Glaucoma; Epinephrine; Vasoconstrictor Agents; Genes, cdc; Trabeculectomy; Fibroblasts
PubMed: 37429521
DOI: 10.1016/j.exer.2023.109561 -
Expert Review of Gastroenterology &... Dec 2023Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high... (Review)
Review
INTRODUCTION
Hepatorenal syndrome (HRS)-acute kidney injury (HRS-AKI) is a specific type of kidney injury seen in patients with cirrhosis and ascites and is associated with high mortality and morbidity. It is characterized by rapid deterioration of renal function due to reduced renal blood flow secondary to portal hypertensive splanchnic and systemic vasodilation. Early diagnosis and treatment of HRS-AKI are associated with greater likelihood of improvement in renal function, lower need for dialysis, and better post-transplant outcomes.
AREAS COVERED
This review discusses the diagnostic criteria for HRS-AKI, which has undergone several key changes over the last decade, with an aim to secure an early diagnosis and aid swift treatment initiation. Additionally, this review outlines the current treatment paradigms for HRS-AKI.
EXPERT OPINION
In the last 20 years, there have been several advances in understanding the pathophysiology and natural course of HRS-AKI. These have led to critical changes in its definition and diagnostic algorithm. However, prognosis of HRS-AKI remains dismal with no significant improvement in HRS-AKI reversal or HRS-related mortality over this time. We discuss several gaps in the current understanding and management of HRS-AKI that will benefit from further research.
Topics: Humans; Hepatorenal Syndrome; Liver Cirrhosis; Kidney; Liver Transplantation; Acute Kidney Injury; Vasoconstrictor Agents
PubMed: 37982156
DOI: 10.1080/17474124.2023.2284189 -
Shock (Augusta, Ga.) Oct 2023Objective: The objective of this study was to provide an in-depth analysis of the advantages and potential research directions concerning the utilization of terlipressin...
Objective: The objective of this study was to provide an in-depth analysis of the advantages and potential research directions concerning the utilization of terlipressin (TP) in combination with norepinephrine (NE) for the management of septic shock. Methods: A systematic search was conducted across five major electronic databases, namely, PubMed, Cochrane, Embase, ScienceDirect, and MEDLINE, using the Boolean method. The search encompassed articles published until May 22, 2023. Randomized controlled trials investigating the efficacy of TP combined with NE in the treatment of patients with septic shock were considered for inclusion. Results: A total of seven trials met the inclusion criteria. The combination therapy of TP and NE exhibited potential benefits in the treatment of adult patients suffering from septic shock. Furthermore, the concurrent administration of TP with NE demonstrated improvements in cardiac output and central venous pressure. However, it is important to acknowledge the presence of certain risks and potential adverse events, including an elevated risk of peripheral ischemia. Conclusions: The available evidence supports the notion that early combination therapy involving NE and TP holds promise in terms of reducing the required dosage of NE, enhancing renal perfusion, and improving microcirculation in patients diagnosed with septic shock.
Topics: Adult; Humans; Norepinephrine; Terlipressin; Shock, Septic; Lypressin; Combined Modality Therapy; Vasoconstrictor Agents
PubMed: 37548701
DOI: 10.1097/SHK.0000000000002204 -
International Journal of Molecular... Aug 2023The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for... (Review)
Review
The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of the tumor microenvironment, nor-adrenaline (NA) is poured in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surfaces of cancer and immune cells and are often involved in the activation of pro-tumoral signaling pathways. Beta2-adrenergic receptors (β2-ARs) are an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate regulatory immune cells and inhibit effector immune cells. Blocking β2-AR increases activation, proliferation, and cytokine release of T lymphocytes. Moreover, β2-AR deficiency during metabolic reprogramming of T cells increases mitochondrial membrane potential and biogenesis. In the view of the available research data, the immunosuppressive role of β2-AR in T cells presents it as a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged the contemporary knowledge about adrenergic-stress-mediated β2-AR activation on T lymphocytes inside tumor milieu.
Topics: Receptors, Chimeric Antigen; T-Lymphocytes; Adrenergic Agents; Norepinephrine; Cell- and Tissue-Based Therapy; Epinephrine
PubMed: 37629018
DOI: 10.3390/ijms241612837 -
Kidney360 Aug 2023Hepatorenal syndrome type 1 (HRS-1) is an often fatal, but potentially reversible, kidney failure in patients with decompensated cirrhosis. Treatment with terlipressin...
KEY POINTS
Hepatorenal syndrome type 1 (HRS-1) is an often fatal, but potentially reversible, kidney failure in patients with decompensated cirrhosis. Treatment with terlipressin in patients with HRS-1 is associated with a reduction in the need for RRT.
BACKGROUND
Hepatorenal syndrome type 1 (HRS-1)—also known as hepatorenal syndrome-AKI (HRS-AKI)—is a rapidly progressing and usually fatal, but potentially reversible, kidney failure occurring in patients with decompensated cirrhosis. A large proportion of patients with HRS-1 require renal replacement therapy (RRT). Terlipressin demonstrated efficacy in reversing HRS and improving renal function in patients with HRS-1 in three phase III, randomized, clinical trials (RCTs; , OT-0401, REVERSE, and CONFIRM). However, these RCTs were not designed to evaluate the effect of terlipressin on the requirement of RRT. In this study, the effect of terlipressin on RRT requirements in the pooled phase III patient population was assessed.
METHODS
For this retrospective analysis, data from patients who participated in the OT-0401, REVERSE, and CONFIRM studies were integrated in the largest-to-date randomized database (=608).
RESULTS
The need for RRT was significantly decreased in patients in the terlipressin group versus the placebo group by day 30 (28.1% versus 35.9%, respectively; = 0.040) and day 60 (30.1% versus 37.9%, respectively; = 0.045) in the pooled population and also postliver transplantation (LT) at day 60 (20.5% versus 40.3%, respectively; = 0.008) and day 90 (25.3% versus 43.1%, respectively; = 0.018). More patients were alive and RRT-free by day 90 in the overall population (36.9% versus 28.5%; = 0.030) and among patients who received an LT (60.0% versus 39.7%; = 0.010). Random assignment to receive terlipressin was an independent positive predictor of avoidance of RRT ( = 0.042); while higher baseline serum creatinine (sCr) level and Child-Pugh scores were negatively associated with RRT avoidance ( < 0.001 and = 0.040, respectively).
CONCLUSIONS
Terlipressin decreased the requirement of RRT compared with placebo among patients with HRS-1, including those receiving LT. A lower sCr level at the beginning of therapy was associated with avoidance of RRT.
Topics: Humans; Terlipressin; Hepatorenal Syndrome; Vasoconstrictor Agents; Lypressin; Continuous Renal Replacement Therapy
PubMed: 37143199
DOI: 10.34067/KID.0000000000000132 -
Current Opinion in Allergy and Clinical... Aug 2024Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and... (Review)
Review
PURPOSE OF REVIEW
Perioperative hypersensitivity reactions are rare but potentially catastrophic events. This review acts to summarize recent recommendations for both immediate and poststabilization management of suspected reactions, alongside practical advice for anaesthetists who may be faced with these events.
RECENT FINDINGS
Prompt treatment is essential but may be hampered by delay in recognition. This can occur because there are multiple differential diagnoses for the observed clinical signs as well as variations in clinical presentation. Resuscitation is dependent on the use of adrenaline and fluids. Adrenaline should be administered in small, titrated intravenous boluses. Low-dose infusions should be commenced early if the response to boluses is poor. Large volume fluid resuscitation may be required to maintain adequate circulating volume. Chest compressions are recommended when there is evidence of inadequate perfusion, rather than waiting until cardiac arrest is confirmed. Antihistamines and corticosteroids are no longer recommended in the immediate management phase. Once the patient has been stabilized, it is important to obtain serial tryptase concentrations to aid the subsequent clinic investigation. The decision to proceed or abandon surgery will be based on an individual risk-benefit analysis. All cases of suspected perioperative hypersensitivity, including fatal cases, must be referred for formal investigation.
SUMMARY
There have been recent updates to management guidelines in perioperative hypersensitivity. Treatment algorithms, treatment packs and referral packs can all help the anaesthetist manage these complex cases, aid the subsequent investigation and ensure patient safety in the future.
Topics: Humans; Epinephrine; Perioperative Period; Anaphylaxis; Practice Guidelines as Topic; Hypersensitivity; Adrenal Cortex Hormones; Drug Hypersensitivity
PubMed: 38814699
DOI: 10.1097/ACI.0000000000001000 -
Peptides Jul 2024Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus... (Review)
Review
Circadian rhythms optimally regulate numerous physiological processes in an organism and synchronize them with the external environment. The suprachiasmatic nucleus (SCN), the center of the circadian clock in mammals, is composed of multiple cell types that form a network that provides the basis for the remarkable stability of the circadian clock. Among the neuropeptides expressed in the SCN, arginine vasopressin (AVP) has attracted much attention because of its deep involvement in the function of circadian rhythms, as elucidated in particular by studies using genetically engineered mice. This review briefly summarizes the current knowledge on the peptidergic distribution and topographic neuronal organization in the SCN, the molecular mechanisms of the clock genes, and the relationship between the SCN and peripheral clocks. With respect to the physiological roles of AVP and AVP-expressing neurons, in addition to a sex-dependent action of AVP in the SCN, studies using AVP receptor knockout mice and mice genetically manipulated to alter the clock properties of AVP neurons are summarized here, highlighting its importance in maintaining circadian homeostasis and its potential as a target for therapeutic interventions.
Topics: Animals; Arginine Vasopressin; Suprachiasmatic Nucleus; Homeostasis; Circadian Rhythm; Humans; Mice; Circadian Clocks; Neurons; Mice, Knockout; Receptors, Vasopressin
PubMed: 38663583
DOI: 10.1016/j.peptides.2024.171229