Uso de vasopresina en el postoperatorio de cirugía de Fontan: inferencias sobre morbimortalidad / Vasopressin use in postoperative Fontan surgery: implications for morbidity and mortality

Introducción: Se ha postulado que el uso de vasopresina tendría efectos beneficiosos en el postoperatorio de cirugía cardiovascular. Objetivo: Evaluar la respuesta a la vasopresina en el postoperatorio (POP) de cirugía de Fontan de nuestra población. Métodos: Estudio de casos y controles anidados en una cohorte retrospectiva. Se incluyeron pacientes con cirugía de Fontan entre 2014 y 2019. Se registraron variables demográficas, datos del cateterismo pre-Fontan, días de asistencia respiratoria mecánica (ARM), necesidad de inotrópicos, diuréticos, diálisis, dieta hipograsa, octreotide, sildenafil y nutrición parenteral total (NPT); balance de fluidos al primer y segundo día POP, necesidad de cateterismo en el POP, días de permanencia de tubo pleural, días de internación, necesidad de reinternación y mortalidad. Se compararon los grupos con y sin vasopresina utilizando la prueba de Mann- Whitney-Wilcoxon test. Se consideró significativa una p < 0.05. Resultados: Del total analizado, 35 pacientes recibieron vasopresina. En el grupo control fueron 58 pacientes con características similares de gravedad sin vasopresina. No se encontraron diferencias en la evolución postoperatoria entre ambos grupos. El grupo con vasopresina recibió en mayor proporción dieta hipograsa. Conclusiones: En nuestra serie el uso de vasopresina no marcó diferencias significativas en términos de morbimortalidad con relación al grupo control (AU)

Introduction: The use of vasopressin has been suggested to have beneficial effects in the postoperative period after cardiovascular surgery. Objective: To evaluate the response to vasopressin in the postoperative period (POP) of Fontan surgery in our population. Methods: Nested case-control study in a retrospective cohort. Patients who underwent Fontan surgery between 2014 and 2019 were included. Demographic variables, pre-Fontan catheterization data, days of mechanical ventilation (MRA), need for inotropics, diuretics, dialysis, low-fat diet, octreotide, sildenafil and total parenteral nutrition (TPN); fluid balance at first and second day POP, need for catheterization at POP, duration of chest tube drainage, days of hospitalization, need for readmission, and mortality were recorded. Groups with and without vasopressin were compared using the Mann-Whitney- Wilcoxon test. A p < 0.05 was considered significant. Results: Of all patients analyzed, 35 received vasopressin. The control group consisted of 58 patients with similar severity characteristics who did not receive vasopressin. No differences were found in the postoperative outcome between the two groups. The vasopressin group received a higher proportion of low-fat diet. Conclusions: In our series the use of vasopressin did not show significant differences in terms of morbidity and mortality compared to the control group (AU)

Compromised regulation of the rat brain parenchymal arterioles in vasopressin-associated acute hyponatremia.

OBJECTIVE: In this study, we examined the effect of acute hyponatremia associated with vasopressin (AVP) on the responses of the isolated rat's MCAs and PAs to acidosis, nitric oxide donor (SNAP) and to endothelium-dependent vasodilator ATP. METHODS: The studies were performed on isolated, perfused and pressurized MCAs and PAs in control conditions and during AVP-associated hyponatremia. Hyponatremia was induced in vitro by lowering Na+ concentration from 144 to 121 mmol/L in intra- and extravascular fluid in the presence of AVP. RESULTS: Parenchymal arterioles showed greater response to an increase in H+ and K+ ions concentration and to ATP in comparison with MCAs in control normonatremic conditions. Both PAs and MCAs constricted in response to acute hyponatremia associated with AVP. Interestingly, disordered regulation of vascular tone was observed in PAs but not in MCAs. The abnormalities in the regulation comprised a significant reduction of PA response to acidosis and the absence of the response to the administration of SNAP or ATP. CONCLUSIONS: Arginine vasopressin-associated hyponatremia leads to constriction and dysregulation of PAs which may impair neurovascular coupling.

In Silico design of AVP (4-5) peptide and synthesis, characterization and in vitro activity of chitosan nanoparticles.

BACKGROUND: Arginine-vasopressin (AVP) is a neuropeptide and provides learning and memory modulation. The AVP (4-5) dipeptide corresponds to the N-terminal fragment of the major vasopressin metabolite AVP (4-9), has a neuroprotective effect and used in the treatment of Alzheimer's and Parkinson's disease. METHODS: The main objective of the present study is to evaluate the molecular mechanism of AVP (4-5) dipeptide and to develop and synthesize chitosan nanoparticle formulation using modified version of ionic gelation method, to increase drug effectiveness. For peptide loaded chitosan nanoparticles, the synthesized experiment medium was simulated for the first time by molecular dynamics method and used to determine the stability of the peptide, and the binding mechanism to protein (HSP70) was also investigated by molecular docking calculations. A potential pharmacologically features of the peptide was also characterized by ADME (Absorption, Distribution, Metabolism and Excretion) analysis. The characterization, in vitro release study, encapsulation efficiency and loading capacity of the peptide loaded chitosan nanoparticles (CS NPs) were performed by Dynamic Light Scattering (DLS), UV-vis absorption (UV), Scanning Electron Microscopy (SEM), Fourier transform infrared (FT-IR) spectroscopy techniques. Additionally, in vitro cytotoxicity of the peptide on human neuroblastoma cells (SH-SY5Y) was examined with XTT assay and the statistical analysis was evaluated. RESULTS: The results showed that; hydrodynamic size, zeta potential and polydispersity index (PdI) of the peptide-loaded CS NPs were 167.6 nm, +13.2 mV, and 0.211, respectively. In vitro release study of the peptide-loaded CS NPs showed that 17.23% of the AVP (4-5)-NH2 peptide was released in the first day, while 61.13% of AVP (4-5)-NH2 peptide was released in the end of the 10th day. The encapsulation efficiency and loading capacity were 99% and 10%, respectively. According to the obtained results from XTT assay, toxicity on SHSY-5Y cells in the concentration from 0.01 µg/µL to 30 µg/µL were evaluated and no toxicity was observed. Also, neuroprotective effect was showed against H2O2 treatment. CONCLUSION: The experimental medium of peptide-loaded chitosan nanoparticles was created for the first time with in silico system and the stability of the peptide in this medium was carried out by molecular dynamics studies. The binding sites of the peptide with the HSP70 protein were determined by molecular docking analysis. The size and morphology of the prepared NPs capable of crossing the blood-brain barrier (BBB) were monitored using DLS and SEM analyses, and the encapsulation efficiency and loading capacity were successfully performed with UV Analysis. In vitro release studies and in vitro cytotoxicity analysis on SHSY-5Y cell lines of the peptide were conducted for the first time. Grapical abstract.

ß-Arrestin 2 mediates arginine vasopressin-induced IL-6 induction via the ERK1/2-NF-κB signal pathway in murine hearts.

Evidence to date suggests that ß-arrestins act beyond their role as adapter proteins. Arginine vasopressin (AVP) may be a factor in inflammation and fibrosis in the pathogenesis of heart failure. In the present study we investigated the effect of AVP on inflammatory cytokine IL-6 production in murine hearts and the impact of ß-arrestin 2-dependent signaling on AVP-induced IL-6 production. We found that administration of AVP (0.5 U/kg, iv) markedly increased the levels of IL-6 mRNA in rat hearts with the maximum level occurred at 6 h. In ß-arrestin 2 KO mouse hearts, deletion of ß-arrestin 2 decreased AVP-induced IL-6 mRNA expression. We then performed in vitro experiments in adult rat cardiac fibroblasts (ARCFs). We found that AVP (10-9-10-6 M) dose-dependently increased the expression of IL-6 mRNA and protein, activation of NF-κB signaling and ERK1/2 phosphorylation, whereas knockdown of ß-arrestin 2 blocked AVP-induced IL-6 increase, NF-κB activation and ERK1/2 phosphorylation. Pharmacological blockade of ERK1/2 using PD98059 diminished AVP-induced NF-κB activation and IL-6 production. The selective V1A receptor antagonist SR49059 effectively blocked AVP-induced NF-κB phosphorylation and activation as well as IL-6 expression in ARCFs. In AVP-treated mice, pre-injection of SR49059 (2 mg/kg, iv) abolished AVP-induced NF-κB activation and IL-6 production in hearts. The above results suggest that AVP induces IL-6 induction in murine hearts via the V1A receptor-mediated ß-arrestin2/ERK1/2/NF-κB pathway, thus reveal a novel mechanism of myocardial inflammation in heart failure involving the V1A/ß-arrestin 2/ERK1/2/NF-κB signaling pathway.

AVP(4-8) Improves Cognitive Behaviors and Hippocampal Synaptic Plasticity in the APP/PS1 Mouse Model of Alzheimer's Disease.

Memory deficits with aging are related to the neurodegeneration in the brain, including a reduction in arginine vasopressin (AVP) in the brain of patients with Alzheimer's disease (AD). AVP(4-8), different from its precursor AVP, plays memory enhancement roles in the CNS without peripheral side-effects. However, it is not clear whether AVP(4-8) can improve cognitive behaviors and synaptic plasticity in the APP/PS1 mouse model of AD. Here, we investigated for the first time the neuroprotective effects of AVP(4-8) on memory behaviors and in vivo long-term potentiation (LTP) in APP/PS1-AD mice. The results showed that: (1) APP/PS1-AD mice had lower spontaneous alternation in the Y-maze than wild-type (WT) mice, and this was significantly reversed by AVP(4-8); (2) the prolonged escape latency of APP/PS1-AD mice in the Morris water maze was significantly decreased by AVP(4-8), and the decreased swimming time in target quadrant recovered significantly after AVP(4-8) treatment; (3) in vivo hippocampal LTP induced by high-frequency stimulation had a significant deficit in the AD mice, and this was partly rescued by AVP(4-8); (4) AVP(4-8) significantly up-regulated the expression levels of postsynaptic density 95 (PSD95) and nerve growth factor (NGF) in the hippocampus of AD mice. These results reveal the beneficial effects of AVP(4-8) in APP/PS1-AD mice, showing that the intranasal administration of AVP(4-8) effectively improved the working memory and long-term spatial memory of APP/PS1-AD mice, which may be associated with the elevation of PSD95 and NGF levels in the brain and the maintenance of hippocampal synaptic plasticity.

Effect of Low-Dose Supplementation of Arginine Vasopressin on Need for Blood Product Transfusions in Patients With Trauma and Hemorrhagic Shock: A Randomized Clinical Trial.

Importance: Current therapies for traumatic blood loss focus on hemorrhage control and blood volume replacement. Severe hemorrhagic shock, however, is associated with a state of arginine vasopressin (AVP) deficiency, and supplementation of this hormone may decrease the need for blood products in resuscitation. Objective: To determine whether low-dose supplementation of AVP in patients with trauma (hereinafter referred to as trauma patients) and with hemorrhagic shock decreases their need for transfused blood products during resuscitation. Design, Setting, and Participants: This randomized, double-blind placebo-controlled clinical trial included adult trauma patients (aged 18-65 years) who received at least 6 U of any blood product within 12 hours of injury at a single urban level 1 trauma center from May 1, 2013, through May 31, 2017. Exclusion criteria consisted of prehospital cardiopulmonary resuscitation, emergency department thoracotomy, corticosteroid use, chronic renal insufficiency, coronary artery disease, traumatic brain injury requiring any neurosurgical intervention, pregnancy, prisoner status, or AVP administration before enrollment. Data were analyzed from May 1, 2013, through May 31, 2017, using intention to treat and per protocol. Interventions: After administration of an AVP bolus (4 U) or placebo, participants received AVP (≤0.04 U/min) or placebo for 48 hours to maintain a mean arterial blood pressure of at least 65 mm Hg. Main Outcomes: The primary outcome was total volume of blood product transfused. Secondary end points included total volume of crystalloid transfused, vasopressor requirements, secondary complications, and 30-day mortality. Results: One hundred patients underwent randomization (49 to the AVP group and 51 to the placebo group). Patients were primarily young (median age, 27 years [interquartile range {IQR}, 22-25 years]) and male (n = 93) with penetrating trauma (n = 79). Cohort characteristics before randomization were well balanced. At 48 hours, patients who received AVP required significantly less blood products (median, 1.4 [IQR, 0.5-2.6] vs 2.9 [IQR, 1.1-4.8] L; P = .01) but did not differ in requirements for crystalloids (median, 9.9 [IQR, 7.9-13.0] vs 11.0 [8.9-15.0] L; P = .22) or vasopressors (median, 400 [IQR, 0-5900] vs 1400 [IQR, 200-7600] equivalent units; P = .22). Although the groups had similar rates of mortality (6 of 49 [12%] vs 6 of 51 [12%]; P = .94) and total complications (24 of 44 [55%] vs 30 of 47 [64%]; P = .37), the AVP group had less deep venous thrombosis (5 of 44 [11%] vs 16 of 47 [34%]; P = .02). Conclusions and Relevance: Low-dose AVP during the resuscitation of trauma patients in hemorrhagic shock decreases blood product requirements. Additional research is necessary to determine whether including AVP improves morbidity or mortality. Trial Registration: ClinicalTrials.gov identifier: NCT01611935.

Background anaesthetic agents do not influence the impact of arginine vasopressin on haemodynamic states and cerebral oxygenation during shoulder surgery in the beach chair position: a prospective, single-blind study.

BACKGROUND: Administration of arginine vasopressin (AVP) is associated with reducing jugular venous (SjvO2) and regional cerebral (rScO2) oxygen saturation under propofol-remifentanil (P/R) anaesthesia. We determined whether background anaesthetics modulate the effect of AVP on cerebral oxygenation and haemodynamics. METHODS: We randomly allocated 60 adult patients scheduled for shoulder surgery in the beach chair position (BCP) into 4 groups, to receive either an intravenous bolus of saline (groups PR-S and SN-S) or 0.05 U/kg AVP (groups PR-AVP and SN-AVP) under P/R or sevoflurane-nitrous oxide (S/N) anaesthesia (n = 15 each). Haemodynamic variables, SjvO2 and rScO2 were measured. RESULTS: AVP significantly increased mean arterial blood pressure (MAP) and decreased rScO2 in either anaesthetic group. AVP also decreased SjvO2 in the P/R groups but not in the S/N groups. The AVP-treated groups showed higher MAP and cerebral desaturation (>20% rScO2 decrease from baseline), along with lower HR and rScO2 in the BCP than those in the saline-treated groups. In contrast, AVP did not affect SjvO2 values or the incidence of SjvO 2  < 50%. Baseline SjvO2 was lower and the magnitude of its reduction in the BCP was greater in the PR-AVP group than in the SN-AVP group, and the lowest SjvO2 values were 37 ± 6 and 57 ± 8%, respectively (P < 0.001). CONCLUSIONS: The choice of anaesthetic regimen did not affect cerebral oxygenation or haemodynamics of AVP in the BCP. However, the negative effect of AVP on cerebral oxygenation should be considered, especially under P/R anaesthesia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01687894 , registered on September 18, 2012.

Transient Intraoperative Central Diabetes Insipidus in Moyamoya Patients Undergoing Revascularization Surgery: A Mere Coincidence?

We present 2 patients with Moyamoya disease undergoing revascularization surgery who developed transient intraoperative central diabetes insipidus with spontaneous resolution in the immediate postoperative period. We speculate that patients with Moyamoya disease may be predisposed to a transient acute-on-chronic insult to the arginine vasopressin-producing portion of their hypothalamus mediated by anesthetic agents. We describe our management, discuss pertinent literature, and offer possible mechanisms of this transient insult. We hope to improve patient safety by raising awareness of this potentially catastrophic complication.

Effects of angiotensin-(1-7) on the proliferation and collagen synthesis of arginine vasopressin-stimulated rat cardiac fibroblasts: role of mas receptor-calcineurin-NF-κB signaling pathway.

: Interstitial fibrosis is a common pathological change in various heart diseases, especially cardiac hypertrophy. Arginine vasopressin (AVP), one of the hallmarks of heart failure, exhibits a profibrotic effect by promoting the proliferation and differentiation of cardiac fibroblasts (CFs). In contrast, angiotensin-(1-7) [Ang-(1-7)] was reported to be beneficial for cardiac remodeling by its antifibrotic effect. To evaluate the effect of Ang-(1-7) on AVP-stimulated CFs and the subsequent signaling molecules involved, CFs isolated from neonatal rat hearts were incubated with AVP and treated with or without Ang-(1-7). Cell proliferation, cell cycle, collagen production, and related cellular signaling molecules were then assessed. The results showed that Ang-(1-7) dose-dependently inhibited cell proliferation and collagen production in AVP-stimulated CFs. In addition, Ang-(1-7) also significantly suppressed calcineurin activity in a dose-dependent manner in AVP-stimulated CFs, which was associated with reduced collagen production. Accordingly, the nuclear translocation and transcriptional activity of nuclear factor-kappa B (NF-κB), downstream signal of calcineurin, were also notably restrained by Ang-(1-7) in AVP-stimulated CFs. Furthermore, the inhibitory effect of Ang-(1-7) on AVP-activated calcineurin-NF-κB signaling was completely reversed by the Mas receptor antagonist A-799. These findings suggest that Ang-(1-7) exerts an antifibrotic effect by inhibiting AVP-stimulated CF proliferation and collagen synthesis by inactivating Mas receptor-calcineurin-NF-κB signaling pathway.

Vasopressin in preeclampsia: a novel very early human pregnancy biomarker and clinically relevant mouse model.

Preeclampsia, a cardiovascular disorder of late pregnancy, is characterized as a low-renin hypertensive state relative to normotensive pregnancy. Because other nonpregnant low-renin hypertensive disorders often exhibit and are occasionally dependent on elevated arginine vasopressin (AVP) secretion, we hypothesized a possible use for plasma AVP measurements in the prediction of preeclampsia. Copeptin is an inert prosegment of AVP that is secreted in a 1:1 molar ratio and exhibits a substantially longer biological half-life compared with AVP, rendering it a clinically useful biomarker of AVP secretion. Copeptin was measured throughout pregnancy in maternal plasma from preeclamptic and control women. Maternal plasma copeptin was significantly higher throughout preeclamptic pregnancies versus control pregnancies. While controlling for clinically significant confounders (age, body mass index, chronic essential hypertension, twin gestation, diabetes mellitus, and history of preeclampsia) using multivariate regression, the association of higher copeptin concentration and the development of preeclampsia remained significant. Receiver operating characteristic analyses reveal that as early as the sixth week of gestation, elevated maternal plasma copeptin concentration is a highly significant predictor of preeclampsia throughout pregnancy. Finally, chronic infusion of AVP during pregnancy (24 ng per hour) is sufficient to phenocopy preeclampsia in C57BL/6J mice, causing pregnancy-specific hypertension, renal glomerular endotheliosis, proteinuria, and intrauterine growth restriction. These data implicate AVP release as a novel predictive biomarker for preeclampsia very early in pregnancy, identify chronic AVP infusion as a novel and clinically relevant model of preeclampsia in mice, and are consistent with a potential causative role for AVP in preeclampsia in humans.

Under general anesthesia arginine vasopressin prevents hypotension but impairs cerebral oxygenation during arthroscopic shoulder surgery in the beach chair position.

BACKGROUND: Patients undergoing surgery in the beach chair position (BCP) are at a risk of cerebral ischemia. We evaluated the effect of arginine vasopressin (AVP) on hemodynamics and cerebral oxygenation during surgery in the BCP. METHODS: Thirty patients undergoing shoulder surgery in BCP under propofol-remifentanil anesthesia were randomly allocated either to receive IV AVP 0.07 U/kg (AVP group, N = 15) or an equal volume of saline (control group, N = 15) 2 minutes before taking BCP. Mean arterial blood pressure (MAP), heart rate (HR), jugular venous bulb oxygen saturation (SjvO2), and regional cerebral tissue oxygen saturation (SctO2) were measured after induction of anesthesia and before (presitting in supine position) and after patients took BCP. RESULTS: AVP itself given before the positioning increased MAP and decreased SjvO2 and SctO2 (P < 0.0001), with HR unaffected. Although MAP was decreased by BCP in both groups, it was higher in the AVP group (P < 0.0001). While in BCP, HR remained unaltered in the control and decreased in the AVP group. SjvO2 in BCP did not differ between the groups. SctO2 was decreased by BCP in both groups, which was more pronounced in the AVP group until the end of study. The incidence of hypotension (13% vs 67%; P = 0.003) was less frequent, and that of cerebral desaturation (>20% SctO2 decrease from presitting value) (80% vs 13%; P = 0.0003) was higher in the AVP group. The incidence of jugular desaturation (SjvO2 <50%) was comparable between the groups. CONCLUSIONS: A prophylactic bolus administration of AVP prevents hypotension associated with BCP in patients undergoing shoulder surgery under general anesthesia. However, it was associated with regional cerebral but not jugular venous oxygen desaturation on upright positioning.

Acute diabetes insipidus mediated by vasopressinase after placental abruption.

CONTEXT: Postpartum, diabetes insipidus (DI) can be part of Sheehan's syndrome or lymphocytic hypophysitis in combination with anterior pituitary hormone deficiencies. In contrast, acute onset of isolated DI in the postpartum period is unusual. CASE PRESENTATION: This patient presented at 33 weeks gestation with placental abruption, prompting a cesarean delivery of twins. Immediately after delivery, she developed severe DI. The DI could be controlled with the vasopressinase-resistant 1-deamino-8-D-arginine vasopressin (DDAVP), but not with arginine vasopressin (AVP), and it resolved within a few weeks. OBJECTIVE: The aim of this study was to demonstrate that the postpartum DI in this patient was caused by the release of placental vasopressinase into the maternal bloodstream. METHODS AND RESULTS: Cells were transiently transfected with the AVP receptor 2 (AVPR2) and treated with either AVP or DDAVP in the presence of the patient's serum collected postpartum or 10 weeks after delivery. The response to the different treatments was evaluated by measuring the activity of a cAMP-responsive firefly luciferase reporter construct. The in vitro studies demonstrate that the patient's postpartum serum disrupts activation of the AVPR2 by AVP, but not by the vasopressinase-resistant DDAVP. CONCLUSIONS: Placental abruption can rarely be associated with acute postpartum DI caused by release of placental vasopressinase into the bloodstream. This clinical entity must be considered in patients with placental abruption and when evaluating patients presenting with DI after delivery.

[Intravenous arginine vasopressin for two pediatric cases of pulmonary hypertension after congenital heart surgery].

We experienced two pediatric cases of severe pulmonary hypertension after congenital heart surgery. It was difficult to wean two cases from cardiopulmonary bypass for systemic hypotension concomitant with pulmonary hypertension reflactory to conventional therapy, including administration of adrenaline, nitroglycerin, milrinone, and/or inhalation of nitric oxide. In order to increase systemic arterial blood pressure and improve severe right heart failure, we administered arginine vasopressin (AVP) intravenously, which is a potent vasoconstrictor via V1 receptor. The dose of AVP was 0.0002 unit x kg(-1) x min(-1). After administration of AVP, systemic arterial pressure increased markedly and pulmonary arterial pressure decreased slightly, and we succeeded in weaning the patients from cardiopulmonary bypass. No adverse effect with AVP was found. In conclusion, administration of AVP is a therapeutic option for treating systemic hypotension concomitant with severe pulmonary hypertension in pediatric congenital heart surgery.

Arginine vasopressin significantly increases the rate of successful organ procurement in potential donors.

BACKGROUND: Hormone replacement therapy increases the number and quality of grafts recovered from brain-dead organ donors. Arginine vasopressin (AVP) has also been shown to have beneficial effects. The aim of this study was to determine the effect of AVP on recovery rates. METHODS: The Organ Procurement and Transplantation Network database was used. Donors treated with hormone replacement therapy and vasopressor agents who were successfully procured between January 1, 2009, and June 30, 2011, were studied. AVP-positive and AVP-negative donors were compared. The primary study end point was the rate of high-yield procurement (≥4 organs). RESULTS: A total of 10,431 donors were included. AVP was infused in 7,873 (75.5%) and was associated with an increased rate of high-yield procurement (50.5% vs 35.6%, P < .001). There was less overall graft refusal due to poor function (38.9% vs 45.6%, P < .001). AVP independently predicted high yield procurement. CONCLUSIONS: The use of AVP with hormone replacement therapy is independently associated with an increased rate of organ recovery. This strategy should be universally adopted in the management of donors progressing to neurologic death.

Intravenous arginine vasopressin infusion in refractory vasodilatory shock: a clinical study.

OBJECTIVE: To assess the efficacy of arginine vasopressin (AVP) as a rescue therapy in children with catecholamine refractory vasodilatory shock and its effect on various hemodynamic, clinical, and laboratory variables. METHODS: This prospective hospital based study was conducted from January 2008 through July 2008 at a tertiary pediatric cardiac critical care unit. Twelve post cardiac surgery patients with advanced vasodilatory shock requiring intravenous vasopressin infusion longer than 60 min were included and continuous vasopressin infusion was given. The primary outcome measures were restoration of Mean arterial blood pressure (MAP) after starting AVP infusion and decrease in other concurrent catecholamines requirement. The secondary outcome measures were survival to hospital discharge, adverse effects, and laboratory variables. RESULTS: Vasopressin was infused in the dose range of 0.0005 to 0.003 units/kg/min for a mean duration of 55.6 h. MAP improved from 41.08 ± 6.15 mmHg at baseline to 48.92 ± 10.05 mmHg after 1 h (P < 0.05), to 57.01 ± 8.30 mmHg after 4 h of AVP infusion (P < 0.001), and to 62.33 ± 8.55 mmHg after 12 h (P < 0.001), which further increased to 71.75 ± 9.55 mmHg after 24 h (P < 0.001). Inotrope score and requirement of other concurrent inotropes declined significantly in all patients after starting AVP infusion (P < 0.001). Lactate levels also declined significantly (P < 0.0001). No significant adverse effect due to end organ ischemia was observed. Only one patient expired while on vasopressin infusion due to refractory hypotension. CONCLUSIONS: Concurrent addition of vasopressin at an appropriate stage help improving MAP significantly with decreased dependence on high dose catecholamines without any significant adverse effects.

Early initiation of arginine vasopressin infusion in neonates after complex cardiac surgery.

OBJECTIVE: To describe our experience with low-dose arginine vasopressin infusions (0.0003 U/kg/min) initiated in the operating room after the Norwood procedure or arterial switch operation. DESIGN: Retrospective cohort study of 37 consecutive neonates. SETTING: Pediatric cardiovascular intensive care unit in a tertiary hospital. SUBJECTS: Nineteen patients that received low-dose arginine vasopressin infusion instituted in the operating room (arginine vasopressin+) were compared to 18 patients that did not receive early arginine vasopressin infusion (arginine vasopressin-). INTERVENTIONS: None. RESULTS: When comparing arginine vasopressin+ and arginine vasopressin- in the first 24 hrs after cardiovascular intensive care unit admission, there was no difference in demographic variables, heart rate, blood pressure, central venous pressure, maximum lactate, maximum arterial and central venous saturation difference, urine output, chest tube output, or peritoneal drain output. Mean fluid resuscitation in the first 24 hrs was significantly lower in the arginine vasopressin+ group compared to the arginine vasopressin- group (182 ± 61 mL/kg vs. 223 ± 53 mL/kg, p = .03). The arginine vasopressin+ group also reached median net negative cumulative fluid balance sooner (55 hrs: interquartile range 45, 74 vs. 76 hrs: interquartile range 69, 92; p = .02). Median maximum inotrope score in the first 24 hrs was significantly lower in arginine vasopressin+ (9: interquartile range 5, 12.5 vs. 16.5: interquartile range 10.3, 22.1; p = .02). There was a nonsignificant trend toward shorter duration of mechanical ventilation and cardiovascular intensive care unit length of stay in the arginine vasopressin+ group. The lowest serum sodium in the first 48 hrs was significantly lower in arginine vasopressin+ (132 vs. 137 mmol/L, p = .01). CONCLUSION: Low-dose arginine vasopressin infusion initiated in the operating room after complex neonatal cardiac surgery was associated with decreased fluid resuscitation and catecholamine requirements in the first 24 postoperative hours.

Plasma copeptin levels before and during exogenous arginine vasopressin infusion in patients with advanced vasodilatory shock.

BACKGROUND: Plasma copeptin levels before and during exogenous arginine vasopressin infusion (AVP) were evaluated, and the value of copeptin levels before AVP therapy to predict complications during AVP therapy and outcome in vasodilatory shock patients was determined. METHODS: This prospective, observational study was nested in a randomized, controlled trial investigating the effects of two AVP doses (0.033 vs. 0.067 IU/min) on the hemodynamic response in patients with advanced vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery. Clinical data, plasma copeptin levels and adverse events were recorded before, 24 hours after and 48 hours after randomization. RESULTS: Plasma copeptin levels were elevated before AVP therapy. During AVP, copeptin levels decreased (P<0.001) in both groups (P=0.73). Copeptin levels at randomization predicted the occurrence of ischemic skin lesions (AUC ROC, 0.73; P=0.04), a fall in platelet count (AUC ROC, 0.75; P=0.01) during AVP and intensive care unit mortality (AUC ROC, 0.67; P=0.04). Twenty-five patients (64.1%) exhibited a decrease in copeptin levels. Patients experiencing a decrease in copeptin levels were older (P=0.04), had a higher Sequential Organ Failure Assessment score count before (P=0.03) and during AVP therapy (P=0.04), had a longer intensive care unit stay (P<0.001) and required AVP therapy longer (P=0.008) than patients without a decrease in copeptin levels during AVP. CONCLUSION: Plasma copeptin levels are elevated in patients with advanced vasodilatory shock. During exogenous AVP therapy, copeptin levels decrease, suggesting suppression of the endogenous AVP system.

Comparing two different arginine vasopressin doses in advanced vasodilatory shock: a randomized, controlled, open-label trial.

PURPOSE: To compare the effects of two arginine vasopressin (AVP) dose regimens on the hemodynamic response, catecholamine requirements, AVP plasma concentrations, organ function and adverse events in advanced vasodilatory shock. METHODS: In this prospective, controlled, open-label trial, patients with vasodilatory shock due to sepsis, systemic inflammatory response syndrome or after cardiac surgery requiring norepinephrine >0.6 microg/kg/min were randomized to receive a supplementary AVP infusion either at 0.033 IU/min (n = 25) or 0.067 IU/min (n = 25). The hemodynamic response, catecholamine doses, laboratory and organ function variables as well as adverse events (decrease in cardiac index or platelet count, increase in liver enzymes or bilirubin) were recorded before, 1, 12, 24 and 48 h after randomization. A linear mixed effects model was used for statistical analysis in order to account for drop-outs during the observation period. RESULTS: Heart rate and norepinephrine requirements decreased while MAP increased in both groups. Patients receiving AVP at 0.067 IU/min required less norepinephrine (P = 0.006) than those infused with AVP at 0.033 IU/min. Arterial lactate and base deficit decreased while arterial pH increased in both groups. During the observation period, AVP plasma levels increased in both groups (both P < 0.001), but were higher in the 0.067 IU/min group (P < 0.001) and in patients on concomitant hydrocortisone. The rate of adverse events and intensive care unit mortality was comparable between groups (0.033 IU/min, 52%; 0.067 IU/min, 52%; P = 1). CONCLUSIONS: A supplementary AVP infusion of 0.067 IU/min restores cardiovascular function in patients with advanced vasodilatory shock more effectively than AVP at 0.033 IU/min.

Vasopressin attenuates TNF-mediated inflammation in the rat cremaster microcirculation.

BACKGROUND: Our previous study in a swine polytrauma model suggested that equieffective systemic pressor doses of arginine vasopressin (AVP) versus phenylephrine (PE) have differential effects on the systemic and cerebral microcirculation. The purpose of this study was to directly observe the effects of AVP versus PE on inflammatory changes evoked by tumor necrosis factor alpha (TNF) in the skeletal muscle microcirculation. METHODS: Seventy-five male rats (180-250 g) were anesthetized with isoforane, intubated and mechanically ventilated with 100% oxygen. The cremaster muscle microcirculation was prepared for intravital video microscopy while being suffused with a heated hetastarch-electrolyte solution. Fluorescein isothiocyanate-labeled albumin (100 mg/kg) was administered intravenously (i.v.) before one of five protocols. In series 1 (n = 20), either AVP (0.2 U/mL) or its vehicle was added to the suffusate for 10 minutes, washed out for 30 minutes, then TNF was suffused (5 ng/mL) for 30 minutes. In series 2 (n = 16), the protocol was similar, except AVP (0.2 U/mL) or an equieffective dose of PE (0.04 mg/mL) was administered i.v. (4.5 mL/h) for 15 minutes before, during, and 45 minutes after TNF suffusion. In series 3 (n = 12), the protocol was similar to series 2, except venous hemorrhage preceded i.v. AVP or PE. In series 4 (n = 15), the protocol was similar to series 3, except an AVP antagonist (vaprisol, 1 mg/kg i.v.) or its vehicle was administered after hemorrhage. In the control series (n = 13), inflammation was evaluated either with a different suffusate (lactated Ringers instead of hetastarch solution), different antigen (histamine instead of TNF), or hemorrhage with no antigen. RESULTS: In series 1, the TNF-evoked increase in leukocyte infiltration (i.e., rolling), leukocyte activation (i.e., sticking), and macromolecular permeability (i.e., albumin extravasation) were attenuated with topical AVP versus vehicle (both p < 0.05), with no effect on venular blood flow (which determines sheer stress). In series 2, the TNF-evoked increase in infiltration, activation, and permeability were all attenuated, and arteriolar blood flow (which determines perfused capillary surface area and hydrostatic pressure) was reduced with i.v. AVP versus i.v. PE (all p < 0.05). In series 3, after hemorrhage to mean arterial pressure <50 mm Hg for 30 minutes, the TNF-evoked increase in infiltration and activation was attenuated, and arteriolar and venular blood flow were both reduced with i.v. AVP versus PE (all p < 0.05). In series 4, after hemorrhage, the TNF-evoked increase in leukocyte activation was potentiated with the vaprisol versus vehicle (p < 0.05) with no effect on arteriolar or venular blood flow. In series 5 (controls), suffusion with lactated Ringers' versus hetastarch solution more than doubled the TNF-evoked increase in activation (p < 0.05). CONCLUSION: (1) AVP can attenuate TNF-evoked leukocyte infiltration, activation or permeability changes in the skeletal muscle microcirculation. (2) The mechanism is probably receptor mediated and does not entirely depend on sheer stress in venules or Starling forces in capillaries. (3) The magnitude of this anti-inflammatory effect is influenced by several conditions, including volume status, the colloid or crystalloid suffusion fluid, and is possibly specific to the antigenic stimulus (TNF vs. histamine).