Comparison of Early Versus Late Adjunctive Vasopressin and Corticosteroids in Patients With Septic Shock.

BACKGROUND: Vasopressin (VP) and hydrocortisone (HC) have been shown to improve outcomes in patients with septic shock. However, there is very little literature addressing the impact of the timing of the combination. OBJECTIVE: This study was conducted to evaluate the impact of early versus late initiation of both VP and HC on time to shock reversal in septic shock patients. METHODS: This was a retrospective study conducted at a tertiary academic medical center. Data were collected from system-generated reports, which were used to identify patients with septic shock who were admitted to an intensive care unit (ICU) and received both VP and HC. The primary endpoint was time to shock reversal. Patients were divided into the "early" group if both VP and HC were initiated within 12 hours of vasopressor initiation or into the "late" group if either VP or HC (or both agents) were initiated after 12 hours of vasopressor initiation. RESULTS: A total of 122 patients were included in the analysis. Early initiation was associated with a shorter time to shock reversal (34 hours vs 65 hours; P = 0.012) compared to late initiation. There were no differences in ICU length of stay, mortality, the number patients requiring renal replacement therapy, or the duration of mechanical ventilation in either group. CONCLUSION AND RELEVANCE: Our study addressed a major gap in the literature and suggests that adding the combination of VP and HC within 12 hours of septic shock may be associated with improved patient outcomes.

Hepatorenal Syndrome-Acute Kidney Injury in Liver Transplantation.

Hepatorenal syndrome (HRS) is a serious complication of cirrhosis. HRS nomenclature has recently changed to HRS-AKI (acute kidney injury). HRS is a complex response to chronic vasodilatory changes brought about by portal hypertension and exacerbated by inflammatory responses that portends poor prognosis to patients with cirrhosis. This syndrome is commonly seen in the setting of infections, particularly spontaneous bacterial peritonitis. Because of the frequency of renal injury in the patient with cirrhosis, HRS-AKI has to be considered high in the differential diagnosis of AKI. Discontinuation of potential triggering agents and elimination of pre-renal AKI, intrinsic renal disease, and structural uropathy as causes of injury are imperative on presentation. Volume expansion with albumin and vasoconstrictive drugs to counteract the underlying splanchnic vasodilation constitutes the most effective medical modality to manage this process. Although the most effective therapy is generally considered to be liver transplantation (LT), the logistic barriers of offering this life-saving therapy on time to all needing it is a major limitation. Terlipressin has been shown to reverse HRS-AKI in a significant proportion of those treated and consequently can lead to increased LT patient survival and freedom from renal replacement therapy. We will review the impact of HRS on the management of patients awaiting LT, present strategies to prevent this significant complication, and discuss major implications of recent therapeutic advances in the setting of LT.

Timing of Vasopressin Addition to Norepinephrine and Efficacy Outcomes in Patients With Septic Shock.

BACKGROUND: Current guidelines recommend norepinephrine as the first-line vasopressor in septic shock followed by addition of vasopressin to achieve a goal mean arterial pressure. Limited evidence exists evaluating how the timing of vasopressin addition affects clinical outcomes in septic shock. OBJECTIVE: The objective of this study was to determine whether the timing of the addition of vasopressin to norepinephrine affects shock resolution. METHODS: This was a multi-site, single system, retrospective cohort, institutional review board (IRB)-approved study examining adult patients with septic shock who received norepinephrine and vasopressin. Patients were divided and statistically analyzed in two subgroups: early vasopressin addition (<3 hours) and late vasopressin addition (≥3 hours). The primary outcome was time to shock resolution, defined as vasopressor free for at least 24 hours. Secondary outcomes included norepinephrine dose at 3 hours after initiation of vasopressin, in-hospital mortality, and intensive care unit length of stay. RESULTS: A total of 243 patients were included in this study. A statistically significant decrease in time to shock resolution was observed in the early vasopressin addition group compared to the late vasopressin addition group (37.6 hours vs 60.7 hours; adjusted hazard ratio [HR]: 2.07 [1.48-2.89; P = <0.001]). The early addition of vasopressin did not affect norepinephrine dose or in-hospital mortality but did lead to a decreased intensive care unit (ICU) length of stay (4.3 days vs 5.3 days, P = 0.02). CONCLUSION AND RELEVANCE: Addition of vasopressin to norepinephrine within 3 hours was associated with a faster time to shock resolution. These findings suggest a potential for improved clinical outcomes with earlier vasopressin addition.

The haemodynamic effects of phenylephrine after cardiac surgery.

BACKGROUND: Phenylephrine increases systemic- and pulmonary resistances and therefore may increase blood pressures at the expense of blood flow. Cardio-pulmonary bypass alters vasoreactivity and many patients exhibit chronotropic insufficiency after cardiac surgery. We aimed to describe the haemodynamic effects of phenylephrine infusion after cardiac surgery. METHODS: Patients in steady state after low-risk cardiac surgery received incremental infusion rates of phenylephrine up to 1.0 µg/kg/min with the aim of increasing systemic mean arterial blood pressure 20 mmHg. Invasive haemodynamic parameters, including pulmonary wedge pressures, were captured along with echocardiographic measures of biventricular function before, during phenylephrine infusion at target systemic blood pressure, and 20 min after phenylephrine discontinuation. RESULTS: Thirty patients were included. Phenylephrine increased mean arterial pressure increased from 78 (±9) mmHg to 98 (±10) mmHg with phenylephrine infusion. Also, pulmonary blood pressure as well as systemic- and pulmonary resistances increased. The ratio between systemic- and pulmonary artery resistances did not change statistically significantly (p = .59). Median cardiac output was 4.35 (interquartile range [IQR] 3.6-5.4) L/min at baseline and increased significantly with phenylephrine infusion (median Δcardiac output was 0.25 [IQR 0.1-0.6] L/min) (p = .012). Pulmonary artery wedge pressure increased from 10.2 (±3.0) mmHg to 11.9 (±3.4) mmHg (p < .001). This was accompanied by significant increases in central venous pressure. Phenylephrine infusion increased left ventricular end-diastolic volume from 105 (±46) mL to 119 (±44) mL (p < .001). All results of phenylephrine infusion were reversed with discontinuation. CONCLUSION: In haemodynamically stable patients after cardiac surgery, phenylephrine increased PVR and SVR, but did not change the PVR/SVR ratio. Phenylephrine increased biventricular filling pressures and left ventricular end-diastolic area. Consequently, CO increased as ejection fraction was maintained. These findings do not discourage the use of phenylephrine after low-risk cardiac surgery. REGISTRATION: clinicaltrial.gov (identifier NCT04419662).

Comparison of Early Versus Late Initiation of Hydrocortisone in Patients With Septic Shock in the ICU Setting.

BACKGROUND: Multiple publications demonstrate an association between time to initiation of corticosteroids and outcomes such as mortality and reversal of shock. However, the optimal time to initiate hydrocortisone remains unknown. OBJECTIVE: To evaluate the impact of early versus late initiation of hydrocortisone in septic shock patients. METHODS: A retrospective, multicentered, observational study was conducted. Adults admitted from July 1, 2014, to August 31, 2019, diagnosed with septic shock receiving vasopressors and low-dose hydrocortisone were evaluated. Participants were divided into the "early" group if hydrocortisone was initiated within 12 hours or "late" group if initiated after 12 hours of vasopressor initiation. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included in-hospital mortality, intensive care unit (ICU) and hospital length of stay (LOS), vasopressor utilization, fluids administered, and need for renal replacement therapy. RESULTS: A total of 198 patients were identified for inclusion in this propensity score-weighted cohort: 99 in the early group and 99 in the late group. Early initiation was associated with shorter time to vasopressor discontinuation compared with late initiation (40.7 vs 60.6 hours; P = 0.0002). There was also a reduction in ICU LOS (3.6 vs 5.1 days; P = 0.0147) and hospital LOS (8.9 vs 10.9 days; P = 0.0220) seen in the early group. There was no difference in mortality between groups. CONCLUSION AND RELEVANCE: In this propensity-matched cohort, administration of hydrocortisone within 12 hours from the onset of septic shock was associated with improved time to vasopressor discontinuation and reduced ICU and hospital LOS.

Vasopressin and Its Analogues: From Natural Hormones to Multitasking Peptides.

Human neurohormone vasopressin (AVP) is synthesized in overlapping regions in the hypothalamus. It is mainly known for its vasoconstricting abilities, and it is responsible for the regulation of plasma osmolality by maintaining fluid homeostasis. Over years, many attempts have been made to modify this hormone and find AVP analogues with different pharmacological profiles that could overcome its limitations. Non-peptide AVP analogues with low molecular weight presented good affinity to AVP receptors. Natural peptide counterparts, found in animals, are successfully applied as therapeutics; for instance, lypressin used in treatment of diabetes insipidus. Synthetic peptide analogues compensate for the shortcomings of AVP. Desmopressin is more resistant to proteolysis and presents mainly antidiuretic effects, while terlipressin is a long-acting AVP analogue and a drug recommended in the treatment of varicose bleeding in patients with liver cirrhosis. Recently published results on diverse applications of AVP analogues in medicinal practice, including potential lypressin, terlipressin and ornipressin in the treatment of SARS-CoV-2, are discussed.

Effect of Vasopressin Dose on Hemodynamic Response in Obese Patients With Septic Shock: A Retrospective Observational Study.

BACKGROUND: No clear association between standard vasopressin doses and body mass index exists, despite potential pharmacokinetic and pharmacodynamic variability among patients with septic shock. It is unknown if higher doses may alter hemodynamic response. OBJECTIVE: The purpose of this study was to evaluate the effect of vasopressin dose on hemodynamic response in obese patients with septic shock. METHODS: A single-center, retrospective cohort study was conducted in adult, obese patients with septic shock receiving catecholamine vasopressors and vasopressin. Patients were analyzed according to vasopressin dose received: standard dose (≤0.04 U/min) and high dose (>0.04 U/min). The primary outcome was percentage change in norepinephrine equivalent (NEQ) dose. RESULTS: A total of 182 patients were included in the analysis, with 136 in the standard-dose vasopressin group and 46 in the high-dose vasopressin group. There was no difference in percentage change in NEQ dose at 6 hours after standard- or high-dose vasopressin attainment (-28.6% vs -19.1%; P = 0.166). A greater increase in mean arterial pressure (MAP) at 6 hours was observed with receipt of high-dose vasopressin (23.3% vs 15.3%; P = 0.023). Duration of shock and length of stay were significantly longer in patients who received high-dose vasopressin, with no difference in in-hospital mortality. CONCLUSION AND RELEVANCE: This represents the first analysis comparing standard and higher doses of vasopressin in obese patients with septic shock. Receipt of high-dose vasopressin was not associated with a difference in catecholamine requirement or improved outcomes. Further studies are warranted to provide guidance on the use of high-dose vasopressin in septic shock.

Vascular actions of peripheral CGRP in migraine-like photophobia in mice.

BACKGROUND: Calcitonin gene-related peptide is recognized as a key player in migraine, yet the mechanisms and sites of calcitonin gene-related peptide action remain unknown. The efficacy of calcitonin gene-related peptide-blocking antibodies as preventative migraine drugs supports a peripheral site of action, such as the trigeminovasculature. Given the apparent disconnect between the importance of vasodilatory peptides in migraine and the prevailing opinion that vasodilation is an epiphenomenon, the goal of this study was to test whether vasodilation plays a role in calcitonin gene-related peptide-induced light aversive behavior in mice. METHODS: Systemic mean arterial pressure and light aversive behavior were measured after intraperitoneal administration of calcitonin gene-related peptide and vasoactive intestinal peptide in wild-type CD1 mice. The functional significance of vasodilation was tested by co-administration of a vasoconstrictor (phenylephrine, endothelin-1, or caffeine) with calcitonin gene-related peptide to normalize blood pressure during the light aversion assay. RESULTS: Both calcitonin gene-related peptide and vasoactive intestinal peptide induced light aversion that was associated with their effect on mean arterial pressure. Notably, vasoactive intestinal peptide caused relatively transient vasodilation and light aversion. Calcitonin gene-related peptide-induced light aversion was still observed even with normalized blood pressure. However, two of the agents, endothelin-1 and caffeine, did reduce the magnitude of light aversion. CONCLUSION: We propose that perivascular calcitonin gene-related peptide causes light-aversive behavior in mice by both vasomotor and non-vasomotor mechanisms.

Patterns in medication incidents: A 10-yr experience of a cross-national anaesthesia incident reporting system.

BACKGROUND: Medication-related adverse events (MRE) in anaesthesia care are frequent and require a deeper understanding if we are to prevent medication harm. METHODS: We searched for reported MRE from the Spanish Anaesthesia Incident Reporting System (SENSAR) database over a 10-yr period. SENSAR is a cross-national, multicentre system focused on perioperative and critical care. A descriptive analysis of independent variables, phase of medication process, type of MRE, and medication group involved, and their relationships with morbidity was conducted. RESULTS: A total of 1970 MRE were identified from 7072 reported incidents. Patient harm was reported in 31% of the MRE. The administration phase was more frequent (42%) and showed the highest harm rate (44%) compared with other medication process phases. The most frequent types of MRE were wrong treatment regimen and wrong medication (55% of cases). The medication groups most commonly reported were those that alter haemostasis (18%), vasoconstrictor agents (13%), and opioids (10%). Vasoconstrictor agents, benzodiazepines, and neuromuscular blocking agents were the medication groups involved in patient harm four-fold more, and opioids three-fold more, than medications that alter haemostasis. The 1970 incidents were investigated and led to implementation of 4223 local corrective patient safety and quality improvement measures. CONCLUSIONS: Patient harm in the perioperative setting from medications remains a major issue for patients, hospital leaders, and clinicians. We found patterns and specific causes that can be mitigated through proven systems solutions, and should be taken into consideration in designing sustainable solutions for safe perioperative care. CLINICAL TRIAL REGISTRATION: NCT03615898.

THE DYNAMICS OF NEUROHUMORAL MEDIATORS OF VASOCONSTRICTION AND VASODILATION AND TROPONIN I IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION DEPENDING ON THE DEGREE OF CONCOMITANT OBESITY.

OBJECTIVE: The aim: Is to evaluate copetin's, MRproADM's and troponin's I dynamic in patients with acute myocardial infarction depending on the degree of concomitant obesity. PATIENTS AND METHODS: Material and methods: The study included 105 patients with AMI. There were formed 2 groups: 1st group of patients with AMI and concomitant obesity (n=75), 2nd group - patients with AMI without obesity (n=30). 37 patients had obesity of the I degree, 38 patients - II degree. The groups were comparable in age and gender. Copeptin, MRproADM, troponin I were determined by enzyme immunoassay method. Data are presented as mean values and the error of the mean (M±m). Differences were considered statistically significant at p<0,05. RESULTS: Results: It was found an increased copeptin's level by 73,8 % (p<0,001) in obesity I degree and by 205,9 % in obesity II degree compared with group with isolated AMI, MRproADM - by 30,68 % (p<0,001) and 54,5 % (p<0,001) respectively. Concentration of copeptin was higher by 76 % (p<0,001) in patients with AMI and II degree obesity comparing to patients with obesity of I degree, and MRproADM - by 18,3% (p<0,001) respectively. Troponin I value fully corresponded the comparison group both in obesity of I degree and II degree (p>0,05). CONCLUSION: Conclusions: The present study provides evidence that a high activity of copeptin and MRproADM in patients with AMI and obesity of I degree with an excessive activity of a marker of vasoconstriction copeptin in conditions of moderate inadequate to the needs MRproADM functioning in patients with obesity of II degree.

A Blast From the Past: Revival of Angiotensin II for Vasodilatory Shock.

OBJECTIVE: To review and summarize data on angiotensin II (AT-II), approved by the Food and Drug Administration (FDA) in December 2017 to increase blood pressure in adults with septic or other distributive shock. DATA SOURCES: A PubMed/MEDLINE search was conducted using the following terms: (angiotensin ii OR angiotensin 2) AND (shock) from 1966 to February 2018. STUDY SELECTION AND DATA EXTRACTION: A total of 691 citations were reviewed with only relevant clinical data extracted. DATA SYNTHESIS: AT-II is a peptide hormone with a multitude of physiological effects-namely, vasoconstriction of venous and arterial smooth muscle. The priority approval granted by the FDA was secondary to a phase 3 study of patients receiving at least 0.2 µg/kg/min of norepinephrine or equivalent for vasodilatory shock. Compared with placebo, AT-II had a significantly higher rate of response, defined as a mean arterial pressure of 75 mm Hg or an increase of 10 mm Hg. No significant difference was found in death by day 28. CONCLUSIONS: AT-II is a newly available vasoactive agent with a novel mechanism for the treatment of distributive shock. Further research is needed to define its exact role in therapy of shock states, identify patients most likely to benefit, and further study its safety profile in critical illness.

Impact of Norepinephrine Weight-Based Dosing Compared With Non-Weight-Based Dosing in Achieving Time to Goal Mean Arterial Pressure in Obese Patients With Septic Shock.

Obesity presents a growing challenge in critically ill patients because of variable medication pharmacokinetics and pharmacodynamics. Vasopressors used in the treatment of septic shock, including norepinephrine, are dosed using weight-based (WB) or non-weight-based (NWB) strategies. Retrospective research has evaluated the effect of total body weight and body mass index on vasopressor requirements, consequently finding that obese patients require less total vasopressor per kilogram to obtain clinical end points such as mean arterial pressure. Although this effect is not completely understood, this may suggest that a NWB dosing strategy is preferred over a WB strategy in obese patients to minimize potential for error.

Effect of Body Weight on Hemodynamic Response in Patients Receiving Fixed-Dose Vasopressin for Septic Shock.

BACKGROUND: Fixed-dose vasopressin is an adjunctive therapy to norepinephrine (NE) to raise mean arterial pressure (MAP) and decrease NE requirements in patients with septic shock. It is unknown if weight affects hemodynamic response to vasopressin or if a weight-based vasopressin strategy is superior to fixed dosing. OBJECTIVE: The primary objective was to evaluate effect of body weight on response to vasopressin as measured by change in MAP 1 hour post-vasopressin initiation. METHODS: A single-center, retrospective study was performed in patients with septic shock. Baseline characteristics, catecholamine and vasopressin requirement, response to therapy, and adverse events were collected. RESULTS: Forty patients were included who received a fixed-dose vasopressin in addition to catecholamine infusions. No correlation was found in the primary outcome of change in MAP at 1 hour after vasopressin initiation compared with vasopressin dose relative to patient weight or body mass index (BMI). Change in MAP at 6 and 12 hours was not significant. In the obese population (n = 9), there was a significant negative correlation between BMI and change in MAP at 6 hours (correlation coefficient r = -0.951; P = 0.0009). Linear regression analysis confirmed that vasopressin dose relative toweight was independently associated with change in MAP at 1, 6, and 12 hours, whereas changes in NE dosing were not. CONCLUSION: Increasing weight-based dosing of vasopressin did not correlate with change in MAP when used with catecholamine vasopressors in septic shock. However, fixed-dose vasopressin may not be sufficient in obese septic shock patients with a BMI ≥30 kg/m(2).

Vasoplegia in sepsis depends on the vascular system, vasopressor, and time-point: a comparative evaluation in vessels from rats subjected to the cecal ligation puncture model.

We evaluated the effects of phenylephrine, norepinephrine, angiotensin II, and vasopressin in mesenteric, renal, carotid, and tail arteries, and in perfused mesenteric vascular bed from rats subjected to the cecal ligation and puncture (CLP) model of sepsis. Phenylephrine and angiotensin II were less efficacious in mesenteric arteries from the CLP 6 h and CLP 18 h groups than in preparations from non-septic animals, but no differences were found for norepinephrine and vasopressin between the preparations. In renal arteries, none of the vasoconstrictors had impaired activity in the CLP groups. Nonetheless, carotid arteries from the CLP 18 h group presented reduced reactivity to all vasoconstrictors tested, but only phenylephrine and norepinephrine had their effects reduced in carotid arteries from the CLP 6 h group. Despite the reduced responsiveness to phenylephrine, tail arteries from septic rats were hyperreactive to vasopressin and norepinephrine at 6 h and 18 h after the CLP surgery, respectively. The mesenteric vascular bed from CLP groups was hyporeactive to phenylephrine, norepinephrine, and angiotensin II, but not to vasopressin. The vascular contractility in sepsis varies from the well-described refractoriness, to unaltered or even hyperresponsiveness to vasoconstrictors, depending on the vessel, the vasoactive agent, and the time period evaluated.

Topical Vasoconstrictors in Cosmetic Rhinoplasty: Comparative Evaluation of Cocaine Versus Epinephrine Solutions.

BACKGROUND: The use of topical vasoconstrictors is a common practice in nasal surgery. These agents reduce bleeding and enable a good surgical field. Topical cocaine and epinephrine, which are frequently used in cosmetic rhinoplasty, are considered safe and effective, but secondary effects have been described. The aim of the present study was to evaluate and compare the benefits and risks of epinephrine and cocaine employed as topical vasoconstrictive agents in cosmetic rhinoplasty. METHODS: This prospective non-randomised study included 65 consecutive female patients undergoing primary closed rhinoplasty. Patients were treated with topical aqueous solutions of 4 % cocaine (n = 33) or 1:1000 epinephrine (n = 32). Benefits and risks of drug use were compared between groups. Vasoconstriction was assessed by quantitative and qualitative evaluation of bleeding during surgery. Systemic effects were studied in terms of cardiovascular changes during the procedure. The Mann-Whitney test and mixed-effects models were used to compare continuous variables and to assess the effects of vasoconstrictor treatment, respectively. RESULTS: Cocaine exerted a stronger and more predictable vasoconstrictive effect than epinephrine. This difference was linked to better field quality, but did not relate to shorter surgery times. Increased heart rate was detected with both agents and was significantly higher with cocaine (p < 0.05). Blood pressure did not significantly differ between groups. CONCLUSIONS: Both cocaine and epinephrine, at the concentrations used in this study, are suitable as topical vasoconstrictive agents in aesthetic rhinoplasty. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Chinese herbal medicine may reduce major adverse cardiovascular events in patients with dialysis hypotension: A taiwan nationwide cohort study.

Background: The association between Chinese herbal medicine (CHM) and the risk of developing major adverse cardiovascular events (MACEs) in patients with dialysis hypotension is unclear and has not yet been investigated. This study aimed to determine whether CMH intervention could reduce the risk of MACEs in patients with dialysis hypotension. Methods: The study data from the Taiwan National Health Insurance Research Database were analyzed to clarify this association. For this study, a case-control design with a cohort of patients who received hemodialysis (HD) from 2008 to 2018, 20 295 HD patients who had received blood pressure (BP) raising drugs were identified. After 1:1 frequency-matching, 730 patients were identified as CHM users and CHM non-users. Vascular access revision/reconstruction and MACEs were observed as the main outcomes during the follow-up period. Results: The occurrence of vascular access revision/reconstruction in HD patients receiving BP raising drugs was associated with a 0.34-fold lower risk in CHM users than in CHM non-users [adjusted hazard ratio (aHR) = 0.34, 95% confidence interval (CI) = 0.26, 0.45]. The occurrences of MACEs in HD patients receiving BP raising drugs was associated with a 0.41-fold lower risk in CHM users than in CHM non-users (aHR = 0.41, 95% CI = 0.33, 0.51). A markedly predominant effect was observed in those receiving CHM for more than 180 days (aHR = 0.32; 95% CI = 0.22, 0.45). Conclusion: The findings revealed lower vascular access dysfunction and MACEs risk correlated with the use of CHM treatment among HD patients who received BP raising drugs.

A comparative review of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia: exploring the factors behind epinephrine's prevalence in the US.

This review paper delves into the comparative study of epinephrine and phenylephrine as vasoconstrictors in dental anesthesia, exploring their histories, pharmacological properties, and clinical applications. The study involved a comprehensive literature search, focusing on articles that directly compared the two agents in terms of efficacy, safety, and prevalence in dental anesthesia. Epinephrine, with its broad receptor profile, has been a predominant choice, slightly outperforming in the context of prolonging dental anesthesia and providing superior hemostasis, which is crucial for various dental procedures. However, the stimulation of beta-adrenergic receptors caused by epinephrine poses risks, especially to patients with cardiovascular conditions. Phenylephrine, a selective alpha-1 adrenergic agonist, emerges as a safer alternative for such patients, avoiding the cardiovascular risks associated with epinephrine. Moreover, its vasoconstrictive effect may not be as deleterious as that of epinephrine, due to its selective action. This review reveals that despite the potential benefits of phenylephrine, epinephrine continues to dominate in clinical settings, due to its historical familiarity, availability, and cost-effectiveness. The lack of commercially available pre-made phenylephrine dental carpules in most countries, except Brazil, and a knowledge gap within dental academia regarding phenylephrine, contribute to its limited use. This review concludes that while both agents are effective, the choice between them should be based on individual patient conditions, availability, and the practitioner's knowledge and familiarity with the agents. The underuse of other vasoconstrictors like levonordefrin and the unavailability of phenylephrine in pre-mixed dental cartridges in many countries highlights the need for further exploration and research in this field. Furthermore, we also delve into the role of levonordefrin and examine the rationale behind the exclusion of phenylephrine from commercially available pre-mixed local anesthetic carpules, suggesting a need for a responsive approach from pharmaceutical manufacturers to the distinct needs of the dental community.

Combination of terlipressin and noradrenaline versus terlipressin in hepatorenal syndrome with early non-response to terlipressin infusion: A randomized trial.

BACKGROUND: Terlipressin and noradrenaline are effective in the management of hepatorenal syndrome (HRS). There are no reports on the combination of these vasoconstrictors in type-1 HRS. AIM: To evaluate terlipressin with or without noradrenaline in type-1 HRS not responding to terlipressin at 48 hours. METHODS: Sixty patients were randomized to receive either terlipressin (group A; n = 30) or a combination of terlipressin and noradrenaline infusion (group B; n = 30). In group A, terlipressin infusion was started at 2 mg/day and increased by 1 mg/day (maximum 12 mg/day). In group B, terlipressin was given at a constant dose of 2 mg/day. Noradrenaline infusion was started at 0.5 mg/h at baseline and increased to 3 mg/h in a stepwise manner. The primary outcome was treatment response at 15 days. Secondary outcomes were 30-day survival, cost-benefit analysis and adverse events. RESULTS: There was no significant difference in the response rate between the groups (50% vs. 76.7%, p = 0.06) and 30-day survival was similar (36.7% vs. 53.3%, p = 0.13). Treatment was more expensive in group A (USD 750 vs. 350, p < 0.001). Adverse events were more frequent in group A (36.7% vs. 13.3%, p < 0.05). CONCLUSIONS: The combination of noradrenaline and terlipressin infusion results in a non-significantly higher rate of HRS resolution with significantly fewer adverse effects in HRS patients who do not respond to terlipressin within 48 hours. CLINICALTRIALS: gov (NCT03822091).

A Systematic Review and Meta-analysis of the Effects of Topical Tranexamic Acid versus Topical Vasoconstrictors on the Management of Epistaxis.

OBJECTIVE: We aimed to evaluate the effectiveness of topical tranexamic acid (TXA) versus topical vasoconstrictors in the management of epistaxis via a systematic review and meta-analysis. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards were followed for the meta-analysis. We systematically searched Embase, Web of Science, Cochrane Library, CNKI, and PubMed for randomized controlled trials (from inception to August 2022; no language restrictions), comparing the effect of topical TXA and topical vasoconstrictors on the treatment of epistaxis. The Q test was used to evaluate heterogeneity, and funnel plots were utilized to identify bias. For the meta-analysis, the fixedeffects model was employed, and the t-test was utilized to determine significance. RESULTS: Of 1012 identified studies, 5 were found to be eligible for our analysis. In total, 598 patients were included; 297 of them received TXA and 301 received vasoconstrictors. Hemostasis was more likely to be achieved at the first re-assessment in patients treated with TXA. Subgroup analysis indicated patients treated with TXA to have less likelihood of bleeding recurrence, compared to patients treated with vasoconstrictors. The detected time interval of rebleeding was 10 min, between 24 h to 72 h, and after 7 days, respectively, and the differences were significant between the two groups of patients treated with TXA and vasoconstrictors. CONCLUSION: Topical TXA was associated with better post-treatment hemorrhagic arrest rates compared to topical vasoconstrictors in the management of epistaxis.

Terlipressin in the management of adults with hepatorenal syndrome-acute kidney injury (HRS-AKI).

INTRODUCTION: Kidney is the most common extra-hepatic organ involved in patients with advanced liver cirrhosis and acute-on-chronic liver failure. Hepatorenal syndrome-acute kidney injury (HRS-AKI) accounts for most hospitalizations, and liver transplantation (LT) remains the ultimate and long-term treatment in such patients. However, HRS-AKI, being a functional renal failure, has a fair chance of reversal, and as such, patients who achieve reversal of HRS-AKI have better outcomes post-LT. AREAS COVERED: In this review, we discuss the pharmacokinetics, pharmacodynamics and evidence to support the use of terlipressin in HRS-AKI while we also address predictors of response and the associated adverse events. Further, we discuss the role of terlipressin in the context of LT. EXPERT OPINION: The recommended treatment for HRS-AKI reversal includes a vasoconstrictor in addition to volume expansion with albumin. The three vasoconstrictor regimens generally used to treat HRS-AKI include octreotide plus midodrine, noradrenaline, and terlipressin. Of these, terlipressin is a widely used drug and has been recently approved by US Food and Drug Administration (USFDA) for HRS-AKI. Terlipressin is the most effective drug for HRS-AKI reversal and is associated with a decreased need for renal replacement therapy pre- and post-transplant. Furthermore, terlipressin responders have improved transplant-free and post-transplant survival.