The REPERFUSE study protocol: The effects of vasopressor therapy on renal perfusion in patients with septic shock-A mechanistically focused randomised control trial.

INTRODUCTION: Acute kidney injury (AKI) is a common complication of septic shock and together these conditions carry a high mortality risk. In septic patients who develop severe AKI, renal cortical perfusion is deficient despite normal macrovascular organ blood flow. This intra-renal perfusion abnormality may be amenable to pharmacological manipulation, which may offer mechanistic insight into the pathophysiology of septic AKI. The aim of the current study is to investigate the effects of vasopressin and angiotensin II on renal microcirculatory perfusion in a cohort of patients with septic shock. METHODS AND ANALYSIS: In this single centre, mechanistically focussed, randomised controlled study, 45 patients with septic shock will be randomly allocated to either of the study vasopressors (vasopressin or angiotensin II) or standard therapy (norepinephrine). Infusions will be titrated to maintain a mean arterial pressure (MAP) target set by the attending clinician. Renal microcirculatory assessment will be performed for the cortex and medulla using contrast-enhanced ultrasound (CEUS) and urinary oxygen tension (pO2), respectively. Renal macrovascular flow will be assessed via renal artery ultrasound. Measurement of systemic macrovascular flow will be performed through transthoracic echocardiography (TTE) and microvascular flow via sublingual incident dark field (IDF) video microscopy. Measures will be taken at baseline, +1 and +24hrs following infusion of the study drug commencing. Blood and urine samples will also be collected at the measurement time points. Longitudinal data will be compared between groups and over time. DISCUSSION: Vasopressors are integral to the management of patients with septic shock. This study aims to further understanding of the relationship between this therapy, renal perfusion and the development of AKI. In addition, using CEUS and urinary pO2, we hope to build a more complete picture of renal perfusion in septic shock by interrogation of the constituent parts of the kidney. Results will be published in peer-reviewed journals and presented at academic meetings. TRIAL REGISTRATION: The REPERFUSE study was registered on Clinical Trials.gov (NCT06234592) on the 30th Jan 24.

Vasopressin in newborns with refractory acute pulmonary hypertension.

BACKGROUND: Acute pulmonary hypertension (aPH) in newborns can be life threatening and challenging to manage. In newborns with refractory aPH, there is currently limited therapeutic agents. METHODS: Retrospective single-center cohort study in newborns less than one month old who were treated with vasopressin for a minimum of one hour in the context of refractory aPH in the neonatal and pediatric intensive care units of a tertiary university center between 2016 and 2022. The objective was to evaluate the efficacy and safety of vasopressin in newborns as an adjuvant treatment for refractory aPH. RESULTS: Twenty-five patients met inclusion criteria. In patients who received vasopressin, oxygenation index improved from 28.4 to 14.4 (p = 0.004) after twelve hours of continuous infusion. Oxygen requirements (FiO2) decreased from 0.91 to 0.50 (p = 0.004) and mean arterial pressure increased from 41 to 51 mmHg (p = 0.001). In our cohort, 68% of patients presented an episode of hyponatremia (serum sodium <130 mmol/L). CONCLUSIONS: The use of vasopressin may be associated with improvement in oxygenation and hemodynamic status of neonatal patients with aPH refractory to initial therapy. Further prospective studies are needed to establish the safety profile of vasopressin in newborns, particularly in preterm infants. IMPACT: Vasopressin may be an effective cardiotropic agent to improve oxygenation and hemodynamic status in newborns with acute pulmonary hypertension. Careful monitoring of serum sodium levels are warranted in newborns who are receiving vasopressin infusion. This provides additional evidence for the consideration of vasopressin in newborns with acute pulmonary hypertension refractory to inhaled nitric oxide.

Null results of oxytocin and vasopressin administration on mentalizing in a large fMRI sample: evidence from a randomized controlled trial.

BACKGROUND: Although potential links between oxytocin (OT), vasopressin (AVP), and social cognition are well-grounded theoretically, most studies have included all male samples, and few have demonstrated consistent effects of either neuropeptide on mentalizing (i.e. understanding the mental states of others). To understand the potential of either neuropeptide as a pharmacological treatment for individuals with impairments in social cognition, it is important to demonstrate the beneficial effects of OT and AVP on mentalizing in healthy individuals. METHODS: In the present randomized, double-blind, placebo-controlled study (n = 186) of healthy individuals, we examined the effects of OT and AVP administration on behavioral responses and neural activity in response to a mentalizing task. RESULTS: Relative to placebo, neither drug showed an effect on task reaction time or accuracy, nor on whole-brain neural activation or functional connectivity observed within brain networks associated with mentalizing. Exploratory analyses included several variables previously shown to moderate OT's effects on social processes (e.g., self-reported empathy, alexithymia) but resulted in no significant interaction effects. CONCLUSIONS: Results add to a growing literature demonstrating that intranasal administration of OT and AVP may have a more limited effect on social cognition, at both the behavioral and neural level, than initially assumed. Randomized controlled trial registrations: ClinicalTrials.gov; NCT02393443; NCT02393456; NCT02394054.

Extended stability of vasopressin 0.2 unit/mL in PVC containers.

PURPOSE: Vasopressin is used to maintain blood pressure in vasodilatory shock. Vasopressin is diluted from concentrated vials prior to administration as a continuous infusion. This study evaluates the physical and chemical stability changes of vasopressin diluted to 0.2 units/mL with 0.9% sodium chloride injection in polyvinyl chloride (PVC) bags stored under refrigeration. METHODS: Vasopressin Injection, USP, 20 unit/mL solution was diluted to 0.2 unit/mL with 0.9% sodium chloride injection, and stability changes were evaluated over 10 days via mass spectrometry on days 0, 7, and 10. RESULTS: Solutions of vasopressin 0.2 unit/mL in 0.9% sodium chloride injection in PVC bags were physically stable and showed less than 10% degradation over 10 days of refrigerated storage. CONCLUSION: Vasopressin 0.2 unit/mL may be given a beyond-use date (BUD) of 10 days based on United States Pharmacopeia BUD recommendations, with this study showing less than 10% degradation over 10 days of refrigerated storage.

Uso de vasopresina y suturas transfixivas para el tratamiento quirúrgico de la gestación ectópica intersticial / Use of vasopressin and transfixive sutures for the surgical treatment of interstitial ectopic gestation

Resumen La gestación cornual, también conocida como intersticial, es una gestación ectópica infrecuente que ocurre en 1/2500 a 1/5000 de los embarazos cuando el embrión implanta en el trayecto intramiometrial de la porción proximal de la trompa. Puede debutar como shock hipovolémico en un 25% de los casos, conllevando una mortalidad de hasta un 2,5%. Mediante ecografía se encuentra un saco gestacional excéntrico y rodeado por una fina capa de miometrio. El tratamiento, en la mayoría de los casos, es quirúrgico, y el control de la hemostasia supone todo un reto. Se presentan dos casos clínicos de mujeres con diagnóstico de gestación intersticial en quienes se realizó exéresis por laparoscopia tras inyección de vasopresina, permitiendo así controlar el sangrado. En una de las pacientes se practicaron también puntos transfixivos transitorios en la arteria uterina y el ligamento útero-ovárico.

Abstract Cornual gestation, also known as interstitial, is a rare ectopic gestation that occurs in 1/2500 to 1/5000 of pregnancies when the embryo implants in the intramyometrial tract of the proximal tube. It can debut as hypovolemic shock in 25% of cases, leading to a mortality rate of up to 2.5%. Using ultrasound, we will find an eccentric gestational sac surrounded by a thin layer of myometrium. Treatment, in most cases, is surgical and control of hemostasis is a challenge. Two clinical cases are presented of women with a diagnosis of interstitial pregnancy in whom transient transfixive sutures were performed at the level of the uterine artery and uterine-ovarian ligament and injection of vasopressin prior to laparoscopic exeresis, thus allowing the bleeding to be controlled.

Vasopressor Discontinuation Order in Septic Shock With Reduced Left Ventricular Function.

BACKGROUND: The optimal vasopressor management for septic patients with left ventricular (LV) dysfunction has not been well established, and current evidence is conflicting regarding the optimal vasopressor discontinuation order. OBJECTIVE: The objective was to evaluate the impact of LV dysfunction on the hemodynamic management of septic shock by assessing the incidence of clinically significant hypotension after vasopressor discontinuation. METHODS: In this single-center, retrospective cohort study, adult patients were included if they met the Sepsis-3 definition of septic shock, had LV dysfunction (defined as an ejection fraction ≤40%), and received norepinephrine and vasopressin as the last vasopressors discontinued. The primary outcome was the incidence of clinically significant hypotension following discontinuation of vasopressin or norepinephrine. Clinically significant hypotension was defined as a MAP less than 60 mmHg and the need for either: 1) the reinstitution of the previously discontinued agent at any dosage, 2) the receipt of at least 500 mL of a crystalloid at a rate of at least 500 mL/hour, 3) or the receipt of at least 25 grams of albumin 5% at a rate of at least 25 gram/hour. Secondary outcomes included intensive care unit (ICU) and hospital lengths of stay, and ICU and hospital mortality. RESULTS: A total of 78 patients met inclusion criteria, with 37 patients having vasopressin discontinued first and 41 having norepinephrine discontinued first. Clinically significant hypotension occurred in 28 patients (76%) following the discontinuation of vasopressin, compared to 28 patients (81%) following the discontinuation of norepinephrine (p = 0.61). ICU length of stay was 9 days in the vasopressin discontinued first cohort, compared to 15 days in the norepinephrine discontinued first cohort (p = 0.01). There was no statistically significant difference in mortality observed. CONCLUSION: The discontinuation order of norepinephrine and vasopressin did not impact the incidence of clinically significant hypotension in patients with septic shock and LV dysfunction, but may influence ICU length of stay, although other factors may have impacted this finding.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Psychotropic drugs upregulate aquaporin-2 via vasopressin-2 receptor/cAMP/protein kinase A signaling in inner medullary collecting duct cells.

Psychotropic drugs may be associated with hyponatremia, but an understanding of how they induce water retention in the kidney remains elusive. Previous studies have postulated that they may increase vasopressin production in the hypothalamus without supporting evidence. In this study, we investigated the possibility of drug-induced nephrogenic syndrome of inappropriate antidiuresis using haloperidol, sertraline, and carbamazepine. Haloperidol, sertraline, or carbamazepine were treated in inner medullary collecting duct (IMCD) suspensions and primary cultured IMCD cells prepared from male Sprague-Dawley rats. The responses of intracellular cAMP production, aquaporin-2 (AQP2) protein expression and localization, vasopressin-2 receptor (V2R) and AQP2 mRNA, and cAMP-responsive element-binding protein (CREB) were tested with and without tolvaptan and the protein kinase A (PKA) inhibitors H89 and Rp-cAMPS. In IMCD suspensions, cAMP production was increased by haloperidol, sertraline, or carbamazepine and was relieved by tolvaptan cotreatment. In primary cultured IMCD cells, haloperidol, sertraline, or carbamazepine treatment increased total AQP2 and decreased phosphorylated Ser261-AQP2 protein expression. Notably, these responses were reversed by cotreatment with tolvaptan or a PKA inhibitor. AQP2 membrane trafficking was induced by haloperidol, sertraline, or carbamazepine and was also blocked by cotreatment with tolvaptan or a PKA inhibitor. Furthermore, upregulation of V2R and AQP2 mRNA and phosphorylated CREB was induced by haloperidol, sertraline, or carbamazepine and was blocked by tolvaptan cotreatment. We conclude that, in the rat IMCD, psychotropic drugs upregulate AQP2 via V2R-cAMP-PKA signaling in the absence of vasopressin stimulation. The vasopressin-like action on the kidney appears to accelerate AQP2 transcription and dephosphorylate AQP2 at Ser261.NEW & NOTEWORTHY It is unclear whether antipsychotic drugs can retain water in the kidney in the absence of vasopressin. This study demonstrates that haloperidol, sertraline, and carbamazepine can produce nephrogenic syndrome of inappropriate antidiuresis because they directly upregulate vasopressin-2 receptor and aquaporin-2 (AQP2) via cAMP/PKA signaling. We showed that, in addition to AQP2 trafficking, AQP2 protein abundance was rapidly increased by treatment with antipsychotic drugs in association with dephosphorylation of AQP2 at Ser261 and accelerated AQP2 transcription.

Angiotensin II and Vasopressin for Vasodilatory Shock: A Critical Appraisal of Catecholamine-Sparing Strategies.

Vasodilatory shock is a serious medical condition that increases the morbidity and mortality of perioperative and critically ill patients. Norepinephrine is an established first-line therapy for this condition, but at high doses, it may lead to diminishing returns. Oftentimes, secondary noncatecholamine agents are required in those whose hypotension persists. Angiotensin II and vasopressin are both noncatecholamine agents available for the treatment of hypotension in vasodilatory shock. They have distinct modes of action and unique pharmacologic properties when compared to norepinephrine. Angiotensin II and vasopressin have shown promise in certain subsets of the population, such as those with acute kidney injury, high Acute Physiology and Chronic Health Evaluation II scores, or those receiving cardiac surgery. Any benefit from these drugs must be weighed against the risks, as overall mortality has not been shown to decrease mortality in the general population. The aims of this narrative review are to provide insight into the historical use of noncatecholamine vasopressors and to compare and contrast their unique modes of action, physiologic rationale for administration, efficacy, and safety profiles.

A double-blind randomized trial on subendometrial injection of vasopressin to control bleeding in postpartum hysterectomy due to abnormally invasive placenta.

OBJECTIVE: To investigate the effect of subendometrial vasopressin injection in patients with abnormally invasive placenta (AIP), who underwent cesarean section and hysterectomy. METHODS: This randomized double-blinded clinical trial was conducted on pregnant women diagnosed with AIP grade 4 and 5 by ultrasonography during cesarean section. Women were randomly divided into two equal groups including group 1 (vasopressin) and group 2 (control) who underwent 20 units of vasopressin and 20 cc normal saline injection, respectively. Vasopressin and placebo were injected subendometrially 1 cm medial to the uterine vessels into the lower uterine segment. The exclusion criteria include presence of myocardial infarction, cardiomyopathy, congestive heart failure, uncontrolled hypertension, chronic obstructive pulmonary disease, pelvic malignancy. The outcome of the study was total quantitative blood loss during the cesarean section. We estimated blood loss by measuring the blood volume in one of the suction bottles with addition for weight changes of mops, pads, and soaked linen savers. RESULTS: Sixty patients were recruited into the study, 30 as the vasopressin group and 30 as the controls; with no excluded case. The amount of bleeding in the vasopressin group was significantly lower compared with that in the control group (P < 0.001). In the vasopressin group, 83.4% of patients had bleeding of less than 1.5 L, while only 3.3% of the control women had bleeding of less than 1.5 L (relative risk = 5). In addition, the number of injected packed cells was lower in the vasopressin group (P < 0.001). CONCLUSION: It was shown that vasopressin injection can help prevent excess hemorrhage and the subsequent risks of anemia or blood transfusions during abdominal hysterectomy in women with AIP.

Effects of Vasopressin Infusion After Pediatric Cardiac Surgery: A Meta-analysis.

Vasopressin has been used to augment blood pressure; however, cardiovascular effects after cardiac surgery have not been well established. The primary objective of this study was to survey the current literature and quantify the pooled effect of vasopressin on hemodynamic parameters in children after pediatric cardiac surgery. A systematic review was conducted to identify studies characterizing the hemodynamic effects of vasopressin after pediatric cardiac surgery. Studies were assessed and those of satisfactory quality with pre- and post-vasopressin hemodynamics for each patient were included in the final analyses. 6 studies with 160 patients were included for endpoints during the first 2 h of infusions. Patients who received vasopressin infusion had greater mean, systolic, and diastolic blood pressures and lower heart rates at 2 h after initiation. 8 studies with 338 patients were included for the effects at 24 h. Patients who received vasopressin infusion had lower central venous pressures and decreased lactate concentrations 24 h after initiation. A subset analysis for children with functionally univentricular hearts found significant decrease in inotrope score and central venous pressure. A subset analysis for neonates found significant decrease in inotrope score and fluid balance. Vasopressin leads to decrease in heart rate and increase in blood pressure in the first 2 h of initiation. Later effects include decrease in inotrope score, central venous pressure, fluid balance, and in lactate within the first 24 h. Findings vary in neonates and in those with functionally univentricular hearts although beneficial effects are noted in both.

Intranasal vasopressin expedites dishonesty in women.

As an integral ingredient of human sociality, dishonesty can be both egocentric and altruistic, as well as gradually escalate. Here, we examined the influence of arginine vasopressin (AVP), a neuropeptide associated with human prosocial behaviors, on dishonest behaviors in men and women. In this double-blind and placebo-controlled study, 101 participants were randomized to administration of either 20 IU intranasal AVP or placebo. We used a two-party task to manipulate the incentive structure of dishonesty in the way of self-/other-serving repeatedly. For lies that benefit both themselves and others, women receiving intranasal AVP lied more than women receiving intranasal placebo and men receiving intranasal AVP. The dishonest behavior of women treated with AVP gradually escalated with repetition over time. These results suggest that AVP selectively regulates the escalation of dishonesty in women, contingent on the motivation of dishonesty. Our findings provide insight into gender-specific modulations of AVP on human dishonest behavior.

Efficacy and safety of corticosteroid therapy in patients with cardiac arrest: a systematic review of randomised controlled trials.

PURPOSES: The role of corticosteroid therapy in patients with cardiac arrest (CA) is uncertain. We aimed to evaluate the efficacy and safety of corticosteroid therapy in CA patients. METHODS: Randomised controlled trials were identified using PubMed, EMBASE, Cochrane Central Register of Controlled Trials, the Chinese National Knowledge Infrastructure and the Chinese Biomedical Literature Database. The primary outcome was overall survival. Secondary outcomes were positive neurological status and probability of sustained restoration of spontaneous circulation (ROSC). Complications were infection and bleeding. Given the significant heterogeneity across previous studies, combining the data using meta-analysis was deemed not appropriate. RESULTS: Five studies (551 patients) met the criteria. Two studies of co-intervention therapy (corticosteroid, vasopressin and epinephrine protocol) found that this approach could benefit in-hospital CA patient survival rates at hospital discharge, improve neurological function at hospital discharge and yield sustained ROSC rate. However, further two studies failed to demonstrate that corticosteroid therapy alone could improve survival and neurological outcomes among CA patients. Additionally, corticosteroid therapy did not increase the risk of infection and bleeding. CONCLUSIONS: Due to the inherent limitations of the studies in this review, we have not been able to reach definitive conclusions. Larger-scale and better-designed studies are therefore recommended, to further evaluate the potential and rational use of corticosteroid therapy in CA patients.

Prognostic capability of the Maximum Acute Gastrointestinal Injury Score and of caloric intake in patients requiring vasopressors: A multicenter prospective cohort study.

PURPOSE: Our main objective was to use the Maximum Acute Gastrointestinal Injury Score (AGImax) to evaluate the prognostic capability of gastrointestinal dysfunction (GID), on hospital mortality in patients on mechanical ventilation (MV) requiring vasopressors. A secondary goal was to analyze the relationship between AGImax and vasopressor dosage with increasing caloric intake. MATERIALS AND METHODS: Prospective multicenter cohort study in ten ICUs across Argentina. Consecutive adult patients on MV, requiring vasopressors and receiving enteral nutrition (EN) were included. AGImax was identified (I-IV) using a modified AGI score. Comparisons of clinical and outcome variables were performed in 3 predetermined EN-groups: <10 kcal/kg/d, ≥10 to <20 kcal/kg/d, or ≥ 20 kcal/kg/d. RESULTS: A total of 494 patients met all inclusion criteria. Forty-four percent of patients had severe AGImax and 17% received <10 kcal/kg/day, indicating more severity and higher mortality. Notable independent predictors of mortality were AGImax, vasopressors, and caloric intake. PN was the only factor which had an inverse relationship to mortality. CONCLUSIONS: In this population, patients with AGImax III-IV were significantly associated with lower caloric intake and greater hospital mortality, highlighting the importance of AGI as a prognostic tool. As PN was linked with lower mortality, it could be an option to explore in further studies.

Oxytocin and vasopressin modulation of prisoner's dilemma strategies.

BACKGROUND: The neuropeptides oxytocin and vasopressin have been repeatedly implicated in social decision making by enhancing social salience and, generally, cooperation. The iterated and sequential version of the prisoner's dilemma (PD) game is a social dilemma paradigm eliciting strategies of cooperation versus competition. AIMS: We aimed to characterise the role of PD players' sex, game partner type (computer vs. human) and oxytocin or vasopressin inhalation on the player's strategy preference. METHODS: Participants (153 men; 151 women) were randomised to intranasal 24 IU oxytocin, 20 IU vasopressin or placebo, double-blind, and played the PD. We examined main and interactive effects of sex, drug and partner type on strategy preference. RESULTS: We found a pervasive preference for a tit-for-tat strategy (i.e. general sensitivity to the partner's choices) over unconditional cooperation, particularly when against a human rather than a computer partner. Oxytocin doubled this sensitivity in women (i.e. the preference for tit-for-tat over unconditional cooperation strategies) when playing against computers, which suggests a tendency to anthropomorphise them, and doubled women's unconditional cooperation preference when playing against humans. Vasopressin doubled sensitivity to the partner's previous choices (i.e. for tit-for-tat over unconditional cooperation) across sexes and partner types. CONCLUSIONS: These findings suggest that women may be more sensitive to oxytocin's social effects of anthropomorphism of non-humans and of unconditional cooperation with humans, which may be consistent with evolutionary pressures for maternal care, and that vasopressin, irrespective of sex and partner type, may be generally sensitising humans to others' behaviour.

Push-Dose Vasopressin for Hypotension in Septic Shock.

BACKGROUND: Peri-intubation cardiac arrest and hypotension in patients with septic shock occur often in the emergency department (ED) and ultimately lead to worse clinical outcomes. In recent years, the use of push-dose, or bolus-dose, vasopressors in the ED have become common practice for transient hypotension and bridging to continuous infusion vasopressors. Push-dose epinephrine and phenylephrine are the agents used most frequently in this scenario. CASE REPORT: A 63-year-old woman who was apneic and pulseless presented to our ED. After 4 min of cardiopulmonary resuscitation, spontaneous circulation was achieved, and the patient was intubated for airway protection. She became hypotensive with a blood pressure of 55/36 mm Hg. After receiving a 1-L bolus of lactated Ringer solution, she remained hypotensive with blood pressure of 80/51 mm Hg and a pulse of 129 beats/min. One unit of intravenous vasopressin push bolus was administered. Within 1 min, her hemodynamics improved to a blood pressure of 141/102 mm Hg and pulse of 120 beats/min. Over the next 2 h, her mean arterial pressure slowly and progressively declined from 120 to 80. No further vasoactive medications were required for approximately 120 min until norepinephrine and vasopressin was initiated for septic shock. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case report discusses the use of push-dose vasopressin as an alternate vasoactive medication to improve hemodynamics in a patient with vasodilatory septic shock.

Use of a Porcine Model to Evaluate the Risks and Benefits of Vasopressors in Propranolol Poisoning.

INTRODUCTION: Vasopressors are a commonly used treatment in beta-blocker poisoning despite evidence they may be ineffective or harmful. The primary objective of the present study is to use previously collected data from two prior studies (high-dose insulin (HDI) versus vasopressin + epinephrine and a placebo-controlled HDI study) to compare survival between vasopressin + epinephrine and placebo. Secondary outcomes included a comparison with HDI as well as comparisons with hemodynamic parameters, including mean arterial pressure (MAP), cardiac output (CO), heart rate (HR), and systemic vascular resistance (SVR). METHODS: Cardiogenic shock was induced in healthy pigs with a bolus of 0.5 mg/kg of intravenous propranolol followed by an infusion of 0.25 mg/kg/minute until the point of toxicity, defined as (0.75 × initial HR × initial MAP), at which point the infusion was reduced to 0.125 mg/kg/minute for 240 (vasopressin + epinephrine or HDI) or 360 minutes (placebo) or until death. RESULTS: Survival was significantly lower in pigs receiving vasopressin + epinephrine (0%, 0/5) than in pigs receiving placebo (50%, 2/4) (p < 0.01). Survival was significantly higher with HDI compared with both groups (100%, 5/5) (p < 0.01). All vasopressin + epinephrine pigs died within 100 minutes after reaching toxicity. Over the course of the resuscitation, we observed a statistically significant steady decrease in CO and HR in the vasopressin + epinephrine group compared with placebo (p < 0.01). In contrast, we observed a statistically significant change in MAP and SVR that followed a parabolic arc, with MAP and SVR rising significantly initially in the vasopressin + epinephrine group then rapidly falling until death (p < 0.01). CONCLUSIONS: Mortality was higher with vasopressors compared with placebo in this porcine model of propranolol poisoning. Further studies are warranted to define the optimal timing and role of vasopressors in beta-blocker poisoning.

Vasopressin Administration Is Associated With Rising Serum Lactate Levels in Patients With Sepsis.

BACKGROUND: Vasopressin is used in conjunction with norepinephrine during treatment of patients with septic shock. Serum lactate is often used in monitoring of patients with sepsis; however, its importance as a therapeutic target is unclear. The objective of this study is to examine the relationship of vasopressin use on serum lactate levels in patients with sepsis. METHODS: This study uses electronic heath records available via the Medical Information Mart for Intensive Care III. Patients were required to have a serum lactate monitoring during the intensive care unit (ICU) stay. The treatment was the administration of vasopressin between hours 3 and 18 of the ICU stay. Analysis was performed using a matched design. RESULTS: Patients receiving vasopressin were more likely to have their serum lactate levels rise when compared to matched patients who did not receive vasopressin (odds ratio: 6.6; 95% confidence interval: 3.0-14.6, P < .001). Patients who received vasopressin had a median increase in serum lactate of 0.3 mmol/L, while patients who did not receive vasopressin had a median decrease in serum lactate of 0.7 mmol/L (P < .001). There was no statistically significant difference between the control and treated groups' lactate trajectories prior to possible administration of vasopressin (P = .15). The results did not change significantly when norepinephrine initiation was used as the index time. CONCLUSIONS: In patients with sepsis, the administration of vasopressin was associated with a statistically significant difference in lactate change over the course of 24 hours when compared to matched patients who did not receive vasopressin.

Efficacy and Safety of Vasopressin as First-Line Treatment of Distributive and Hemorrhagic Shock States.

Background: Norepinephrine remains the first-line option to manage patients with circulatory shock. Limited evidence exists evaluating noncatecholamine compounds as first-line monotherapy for managing noncardiogenic shock. Objective: To compare vasopressin monotherapy with norepinephrine monotherapy for reversal of distributive and hemorrhagic shock. Methods: This was a retrospective cohort study including adult patients who were diagnosed with hypovolemic or septic shock, received fluids, and received norepinephrine or vasopressin monotherapy for at least 1 hour. Patients excluded lacked a clear diagnosis, were initiated on 2 or more vasopressors at once, or underwent cardiac surgery. The primary outcome was time to shock reversal. Secondary outcomes included mortality, lengths of stay, and safety end points. A multivariable Cox proportional hazards model was performed incorporating baseline and treatment variables. Results: A total of 85 and 160 patients were treated with vasopressin and norepinephrine, respectively. A decrease in time to shock reversal was observed in the vasopressin group (58.32 hours [95% CI, 50.88-66.00] vs 74.64 hours [95% CI, 60.96-88.32], P = 0.004). Mortality was lower in the vasopressin group (25% vs 41%, P = 0.01), and intensive care unit length of stay was longer (13 days [interquartile range, IQR = 7-19] vs 7 days [IQR = 5-9], P = 0.006). Remaining secondary outcomes were similar. The multivariable analysis revealed no difference in time to shock reversal. Conclusion and Relevance: First-line vasopressin exhibited faster time to distributive shock reversal in the unadjusted analysis but failed to maintain this difference in the multivariable analysis. These findings support safe use of vasopressin as first-line therapy or as an alternative to norepinephrine in distributive shock.

Mortality, Morbidity, and Costs After Implementation of a Vasopressin Guideline in Medical Intensive Care Patients With Septic Shock: An Interrupted Time Series Analysis.

Background: Vasopressin decreases vasopressor requirements in patients with septic shock. However, the optimal norepinephrine dose for initiation or cessation of vasopressin is unclear. Objective: Analyze monthly intensive care unit (ICU) mortality rates 1 year preimplementation and postimplementation of a guideline suggesting a norepinephrine dose of 50 µg/min or more for initiation of vasopressin and early cessation of vasopressin. Methods: This retrospective quasi-experimental study included adult patients with septic shock admitted to the medical ICU of a tertiary care medical center over 2 years. Time periods were evaluated with interrupted time series analysis. Results: A total of 1148 patients were included: 573 patients preguideline and 575 patients postguideline. Group characteristics were well balanced at baseline, except patients postguideline had higher sequential organ failure assessment scores. Postguideline, fewer patients were initiated on vasopressin (305 [53.2%] vs 217 [37.7%], absolute difference -15.5% [95% CI -21.2% to -9.8%]), and the norepinephrine dose at vasopressin initiation was higher (median 25 [interquartile range 18, 40] µg/min vs 40 [22, 52] µg/min; median difference 15 [95% CI 11 to 19] µg/min; P < 0.01). After guideline implementation, there was no evidence for a difference in ICU mortality rate slope (slope change 0.07% [95% CI -0.8% to 1.0%] per month; P 0.87), but the vasoactive cost level decreased by US$183 (95% CI -US$327 to -US$39) per patient immediately after implementation. Conclusion and Relevance: Implementation of a guideline suggesting a high norepinephrine dose threshold for vasopressin initiation and early vasopressin cessation in patients with septic shock appears to be safe and may decrease vasoactive costs.