Choice Of Vasopressor Research Articles

Vasodilatory shock: a review of pathophysiology and vasopressor therapy

Vasodilatory shock is characterised by a global loss of vasomotor tone, leading to maldistribution of blood volume, low systemic arterial pressure and hypoperfusion. This syndrome can be caused by sepsis, anaphylaxis and a wide range of other aetiologies. This review article explores the pathophysiology of vasodilatory shock, including well-understood mechanisms and emerging avenues of future investigation. Options for vasopressor therapy are reviewed, including evidence from preclinical canine models, small animal clinical research, large human clinical trials and the Surviving Sepsis Campaign. Recommendations for rational vasopressor choice are extrapolated from this evidence. Future directions include the development of novel vasoactive agents, clinical data comparing the safety and effectiveness of vasopressors in small animals and the development of a veterinary-specific consensus statement guiding best practices for the treatment of vasodilatory shock.

CARDIOGENIC SHOCK IN A PATIENT WITH SEVERE AORTIC VALVE STENOSIS AND MULTIVESSEL CORONARY DISEASE: ADVANCED THERAPEUTIC STRATEGIES

Abstract We describe a case of a 58 years old man. He was referred to emergency room for episodes of vomiting and epigastric pain for about a week. Upon admission he was confused with systolic–diastolic blood pressure values ​​70/40 mmHg, heart rate 120 bpm, sinus rhythm. pO2 was 80 mmHg and SO2 in air 97%. Lactate values 10, blood sugar > 300 mg/dl. The electrocardiogram showed sinus tachycardia with the results of antero–septal necrosis and incomplete left bundle branch block. The fast echocardiogram showed a dilated left ventricle with severe depression of the ejection fraction (EF about 10–15%), severe low flow–low gradient aortic valve stenosis (AVA bidimensional was approximately 0.9 cm²), severe mitral valve insufficiency due to a dual mechanism. The dimension of Inferior vena cava was 1.5 cm, collapsible. There was thrombotic stratification in the apex of the left ventricle and VA coupling was 2. The patient was admitted to the ICU with stage C cardiogenic shock according to SCAI classification. We found a value of PVC 3 mmHg. After fluide challenge there was an increase in blood pressure values to 100/60 mmHg. Noradrenaline vasopressor was started and subsequently a low dose of adrenaline. Blood pressure values maintained around 90/60 mmHg and undergo a sudden drop after increasing the dosage of the vasopressor. Diuresis was approximately 50 ml/h, lactates clear completely after approximately 4 hours. After 6 hours, due to a new sudden reduction in blood pressure, the patient was referred for IABP and coronary angiography control. In the context of multivessel coronary artery disease and cardiogenic shock he was therefore a candidate for urgent cardiac surgery of aortic valve replacement, by–pass and mitral anulovalvuloplasty. This case gave us the opportunity to analyze how to proceed in such a critical conditions with the below conclusions: a) the choice of vasopressors and inotropes is limited in case of severe aortic valve stenosis b) the presence of left ventricular intracavitary thrombosis limits the choice of ventricular assistance system c) in case of cardiogenic shock and severe aortic valve stenosis the patient must be a candidate for valve replacement surgery as soon as possible.

Caveat Emptor: Vasopressor Choice and Postoperative Delirium-A Complex Relationship Explored.

Caveat Emptor: Vasopressor Choice and Postoperative Delirium-A Complex Relationship Explored.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on Hemodynamic Management.

Clinical practice guideline development following the GRADE process. Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the "lower limit," but not actively augmented beyond an "upper limit" of 90-95mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the "target MAP" was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG "suggested" that MAP be augmented for a duration of 3-7days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI.

Comparison of metaraminol versus no metaraminol on time to resolution of shock in critically ill patients

ObjectiveThere is limited evidence to support metaraminol use in critically ill patients. Metaraminol is not included as a vasopressor choice in international guidelines for the management of shock. Nevertheless, metaraminol...

The incidence of postoperative vasopressor usage: protocol for a prospective international observational cohort study (SQUEEZE)

BackgroundPostoperative hypotension is common after major non-cardiac surgery, due predominantly to vasodilation. Administration of infused vasopressors postoperatively may often be considered a surrogate indicator of vasodilation. The incidence of postoperative vasopressors has never been described for non-cardiac surgery, nor have outcomes associated with their use. This paper presents a protocol for a prospective international cohort study to address these gaps in knowledge.The primary objectives are to estimate the proportion of patients who receive postoperative vasopressor infusions (PVI) and to document the variation in this proportion between hospitals and internationally. Furthermore, we will identify factors in variation of care (patient, condition, surgery, and intraoperative management) associated with receipt of PVI and investigate how PVI use is associated with patient outcomes, including organ dysfunction, length of hospital stay, and 30-day in-hospital mortality.MethodThis will be a prospective, international, multicentre cohort study that includes all adult (≥ 18 years) non-cardiac surgical patients in participating centres. Patients undergoing cardiac, obstetric, or day-case surgery will be excluded. We will recruit two cohorts of patients: cohort A will include all eligible patients admitted to participating hospitals for seven consecutive days. Cohort B will include 30 sequential patients per hospital, with the single additional inclusion criterion of postoperative vasopressor usage. We expect to collect data on approximately 40,000 patients for cohort A and 12,800 patients for cohort B.DiscussionWhile in cardiac surgery, clinical trials have informed the choice of vasopressors used to treat postoperative vasoplegia; there remains equipoise over the best approach in non-cardiac surgery. Our study will represent the first large-scale assessment of the use of vasopressors after non-cardiac surgery. These data will inform future studies, including trials of different vasopressors and potential management options to improve outcomes and reduce resource use after surgery.Trial registrationClinicalTrials.gov Identifier: NCT03805230, 15 January 2019.

Effects of prophylactic bolus of norepinephrine versus phenylephrine on maternal and fetal outcome during caesarean section under subarachnoid block: A randomized study

Background: Vasopressors are the mainstay of treatment of subarachnoid block-induced hypotension (SAIH). The literature is ambiguous regarding the choice of vasopressor, the strategy of administration, and their potency ratio for proper comparison. A prophylactic bolus dosing is the preferred mode of administration for obstetric anesthesia. Thus, we undertook a study to assess the efficacy of norepinephrine (NE) and phenylephrine (PE) in preventing SAIH and compare their effects on maternal and fetal outcomes. Materials and Methods: A randomized, double-blind clinical study was conducted on 240 parturients planned for elective cesarean section under subarachnoid block (SAB). They were allocated to receive a prophylactic bolus dose of either NE 4 μg or PE 50 μg immediately after the SAB. The incidence of maternal hypotension (primary outcome); heart rate (HR), reactive hypertension, intraoperative nausea or vomiting, neonatal APGAR score, umbilical umblical cord blood pH, and the need for active neonatal resuscitation (secondary outcomes) was compared between the groups. Results: The incidence of hypotension was comparable between the groups (P = 0.42). The mean HR was significantly higher in the NE group at 2 min (83.9 ± 9.2 vs. 80.6 ± 9.3 bpm, P = 0.005), 3 min (84.4 ± 8.8 vs. 79.3 ± 11.1 bpm, P < 0.001) and 4 min (85.0 ± 9.9 vs. 79.6 ± 12.6 bpm, P < 0.001). Rest of the maternal and fetal outcomes were similar in both the groups. Conclusion: Based on the relative potency ratio of 12.5, the effect of an intermittent prophylactic bolus dose of NE is comparable to that of PE in preventing SAIH.

1258: USE OF CAUSAL INFERENCE TO COMPARE NOREPINEPHRINE- AND VASOPRESSIN-RELATED ICU MORTALITY

Introduction: The choice of vasopressor has been studied extensively in septic shock, however limited data exists in other shock types. Norepinephrine and vasopressin were compared in a retrospective study of the cardiac surgery population. Vasopressin as first-line treatment of post-cardiac surgery vasoplegic shock was found to improve clinical outcomes. However, the study was associated with biases which limits its validity. As there are no prospective studies, we use causal inference to analyze retrospective data. An observational study allows individual observation under one treatment scenario, while a counterfactual outcome is unknown. Targeted Maximum Likelihood Estimation (TMLE) models counterfactual outcomes with limited confounding by generating a pseudo-population. By adjusting for common causes of death, we were able to compare mortality outcomes between norepinephrine and vasopressin. Methods: An anonymous, publicly available database was analyzed using pre-existing IRB approval. The eICU Collaborative Research Database contains data on over 200,000 ICU admissions. The analysis used 27,388 patients with 25 initial features. Missing values greater than 50% were dropped. Machine Learning Extensions Library (MLxtend) was used to select features sequentially. The primary outcome was ICU mortality. Imputation was performed using Sklearn Iterative Imputuer, data scaled using Sklearn Standard Scaler. Our primary model was TMLE with Logistic Regression. We analyzed vasopressin and norepinephrine administration, accounting for their co-administration by using them as covariates. Net fluid balance, Apache IV, albumin, admission weight, age, diabetes, and metastatic cancer were confounder covariates for both groups. Before analysis, a causal diagram was constructed based on these covariates. Our primary metric was Average Treatment Effect (ATE). Results: Mortality analysis on the norepinephrine group showed an ATE of -0.179, 95% CI [-0.188, -0.167]. Vasopressin showed an ATE of 0.03 (95% CI [0.01,0.051]). Compared to vasopressin, norepinephrine showed a reduction in mortality. Conclusions: We found that norepinephrine was associated with decreased mortality compared to vasopressin in this setting. We hope this study’s results will help guide prospective studies moving forward.

1249: PREFERRED VASOACTIVE IN THE SETTING OF RIGHT VENTRICULAR FAILURE CAUSED BY PULMONARY HYPERTENSION

Introduction: Available literature does not sufficiently guide vasopressor selection in patients with acute right ventricular failure due to pulmonary hypertension (pHTN). The choice in this population is often based on preference or anecdotal evidence. The primary aim of this study was to evaluate the effect of vasopressor choice, either beta-1 agonists (BA) or non-beta-1 agonists (NBA), on hemodynamic and clinical outcomes in patients with pHTN experiencing right ventricular failure. Methods: This was a retrospective chart review of patients with pHTN experiencing right ventricular failure who required vasopressor support. Cohorts were defined by initial vasopressor choice; BA vasopressors included norepinephrine and epinephrine and NBA vasopressors were phenylephrine and vasopressin. The primary endpoint was days alive and free (DAF) of vasopressors at 28 days. Hemodynamic markers of cardiac function were collected from pulmonary artery catheters to aid in the assessment. Additional endpoints included markers of suboptimal therapy such as elevations in troponins, presence of tachyarrhythmias, addition of vasopressors from the other cohort, and escalation of therapy. Results: Twenty-two patients were included, 9 in the BA cohort and 13 in the NBA cohort. Baseline demographics between the two groups were similar except there was a non-significantly higher proportion of patients in the NBA arm had WHO Group I pHTN (0% vs 31%; p =0.12) and more mechanically ventilated patients in the BA cohort (44% vs 8%; p=0.12). There was no significant difference between the cohorts in respect to DAF of vasopressors. There was an increase in DAF for the NBA cohort (0 vs 17; p=0.57), which may have been significant if additional patients were included. Conclusions: Due to limited sample size, no statistical difference was observed in any outcome between vasopressor cohorts, however this is the largest analysis to date involving this population. A trend toward more DAF of vasopressors in the NBA cohort could be a signal that these vasopressors may be preferred, but prospective studies are needed to confirm this finding.

Abstract 11593: The Critical Role of Transthoracic Echocardiography in the Evaluation of Cardiogenic Shock and Takotsubo Cardiomyopathy

Introduction: Cardiogenic shock occurs in 10% of patients with takotsubo cardiomyopathy (TTC) as a result of severe systolic dysfunction, or left ventricular outflow tract (LVOT) obstruction. Methods: Case report and review of the literature. Results: A 62-year-old female with a history of hypertension and diabetes mellitus presented with lightheadedness, shortness of breath, and chest discomfort. She was hemodynamically unstable, tachycardic, and hypotensive (70/40 mmHg). Her EKG showed sinus tachycardia at 101 BPM with 1 mm ST depression in leads II, III, AVF; V3-V6. Chest radiograph revealed pulmonary edema. High-sensitive troponin was 146.7. She was intubated for respiratory distress and had rapidly increasing vasopressor requirements. Emergent coronary angiography revealed nonobstructive coronary artery disease. A left ventriculogram revealed apical ballooning with an estimated ejection fraction of 25%, consistent with TTC. Transthoracic echocardiogram (TTE) showed severe mid and apical LV hypokinesis with basal hyperkinesis. Additionally, systolic anterior motion (SAM) of the mitral valve (MV) was noted, with a peak LVOT gradient of 7 mmHg. The patient improved clinically, and all support was weaned off. However, she later acutely developed recurrent respiratory distress and hypotension. Repeat TTE showed LVOT obstruction with a gradient of 40 mmHg due to increased basal hyperkinesis and SAM. The choice of vasopressor was switched from norepinephrine to phenylephrine to reduce the obstruction. She clinically improved and metoprolol succinate was added to reduce basal hypercontractility and improve left ventricular filling. Conclusions: Differentiating the mechanism of shock in TTC can easily be accomplished with TTE, and is essential to guiding treatment. The initial acute systolic dysfunction was effectively managed with norepinephrine, dopamine, and an intra-aortic balloon pump. She later developed LVOT obstruction as her systolic function improved. This was recognized with TTE and led to an appropriate change in vasopressor, as norepinephrine would have worsened the obstruction. This highlights the importance of early TTE in patients presenting with undifferentiated shock, especially when TTC is suspected.

Use of vasopressors for treatment of vasodilatory hypotension in dogs and cats by Diplomates of the American College of Veterinary Emergency and Critical Care.

To identify the most common practices of Diplomates of the American College of Veterinary Emergency and Critical Care (DACVECCs) as they relate to the recognition and treatment of hypotension in dogs and cats, particularly concerning the use of vasopressors in vasodilatory shock states. A survey regarding vasopressor use was sent to all active DACVECCs using the Veterinary Information Network. Questions focused on respondent characteristics, method of recognition of hypotension, triggers for initiation of vasopressor therapy, first- and second-line vasopressor choice, and methods of determining response to therapy. A total of 734 DACVECCs were invited to participate, and 203 Diplomates (27.7%) completed the survey. For both dogs and cats, the most common first-line vasopressor was norepinephrine (87.9% in dogs and 83.1% in cats). The most common second-choice vasopressor was vasopressin (44.2% in dogs and 39.0% in cats). Cutoff values for initiating vasopressor therapy varied between species and modality used for blood pressure measurement. In general, most DACVECCs chose to initiate vasopressor therapy at a Doppler blood pressure <90mmHg or a mean arterial pressure of <60 or <65mmHg when using oscillometric or direct arterial blood pressure measurements in dogs and cats. Most DACVECCs adhere to published human guidelines when choosing a first-line vasopressor. However, there is significant variability in blood pressure measurement technique, cutoffs for initiation of vasopressor use, and choice of second-line vasopressors.

Contemporary hemodynamic management of acute spinal cord injuries with intravenous and enteral vasoactive agents: A narrative review.

The pathophysiology and hemodynamic management of acute spinal cord injuries, including the use of intravenous and enteral vasoactive agents, are reviewed. Spinal cord injuries are devastating neurological insults that in the acute setting lead to significant hemodynamic disturbances, including hypotension and bradycardia, that are influenced by the level of injury. High thoracic (usually defined as at or above T6) and cervical injuries often manifest with hypotension and bradycardia due to destruction of sympathetic nervous system activity and unopposed vagal stimulation to the myocardium, whereas lower thoracic injuries tend to result in hypotension alone due to venous pooling. Initial management includes maintaining euvolemia with crystalloids and maintaining or augmenting mean arterial pressure with the use of intravenous vasoactive agents to improve neurological outcomes. Choice of vasopressor should be based on patient-specific factors, particularly level of injury and presenting hemodynamics. This review includes the most recent literature on intravenous vasopressors as well as the limited evidence supporting the use of enteral vasoactive agents. Enteral vasoactive agents may be considered, when clinically appropriate, as a strategy to wean patients off of intravenous agents and facilitate transfer outside of the intensive care unit. The hemodynamic management of acute spinal cord injuries often requires the use of vasoactive agents to meet mean arterial pressure goals and improve neurological outcomes. Patient-specific factors must be considered when choosing intravenous and enteral vasoactive agents.

Early Vasopressor Utilization Strategies and Outcomes in Critically Ill Patients With Severe Traumatic Brain Injury.

Early hypotension after severe traumatic brain injury (sTBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors, commonly norepinephrine and phenylephrine, to support blood pressure after TBI. However, guidelines do not specify vasopressor type, resulting in variation in clinical practice. We describe early vasopressor utilization patterns in critically ill patients with TBI and examine the association between utilization of norepinephrine, compared to phenylephrine, with hospital mortality after sTBI. We conducted a retrospective cohort study of US hospitals participating in the Premier Healthcare Database between 2009 and 2018. We examined adult patients (>17 years of age) with a primary diagnosis of sTBI who were treated in an intensive care unit (ICU) after injury. The primary exposure was vasopressor choice (phenylephrine versus norepinephrine) within the first 2 days of hospital admission. The primary outcome was in-hospital mortality. Secondary outcomes examined included hospital length of stay (LOS) and ICU LOS. We conducted a post hoc subgroup analysis in all patients with intracranial pressure (ICP) monitor placement. Regression analysis was used to assess differences in outcomes between patients exposed to phenylephrine versus norepinephrine, with propensity matching to address selection bias due to the nonrandom allocation of treatment groups. From 2009 to 2018, 24,718 (37.1%) of 66,610 sTBI patients received vasopressors within the first 2 days of hospitalization. Among these patients, 60.6% (n = 14,991) received only phenylephrine, 10.8% (n = 2668) received only norepinephrine, 3.5% (n = 877) received other vasopressors, and 25.0% (n = 6182) received multiple vasopressors. In that time period, the use of all vasopressors after sTBI increased. A moderate degree of variation in vasopressor choice was explained at the individual hospital level (23.1%). In propensity-matched analysis, the use of norepinephrine compared to phenylephrine was associated with an increased risk of in-hospital mortality (OR, 1.65; CI, 1.46-1.86; P < .0001). Early vasopressor utilization among critically ill patients with sTBI is common, increasing over the last decade, and varies across hospitals caring for TBI patients. Compared to phenylephrine, norepinephrine was associated with increased risk of in-hospital mortality in propensity-matched analysis. Given the wide variation in vasopressor utilization and possible differences in efficacy, our analysis suggests the need for randomized controlled trials to better inform vasopressor choice for patients with sTBI.

Knowledge of and Compliance with Surviving Sepsis Campaign Guidelines among Anesthesiologists: A Nationwide Survey in China.

We aimed to describe anesthesiologists' knowledge of and compliance with the Surviving Sepsis Campaign (SSC) guidelines in the perioperative management of patients with sepsis in China. We designed a questionnaire-based, cross-sectional survey. We sent out online questionnaires during 2019 to evaluate whether anesthesiologists in China were familiar with and applied SSC guidelines in perioperative management. We also compared anesthesiologists' knowledge of and compliance with the guidelines among different levels of hospital. In this study, we obtained 971 responses from anesthesiology departments across China. The survey responses showed that 39.0% of anesthesiologists rated their knowledge of the SSC guidelines as being “very familiar” or at least “somewhat familiar.” In total, 68.9% of respondents chose “Initial fluid resuscitation followed by frequent hemodynamic reassessment” as their therapy strategy for patients with septic shock; 62.0% of anesthesiologists chose lactate as a marker of initial resuscitation in clinical practice, and 39.1% thought bundle therapy needed to be started within 1 hour of sepsis diagnosis. A total of 37.1% and 27.1% of respondents chose hydroxyethyl starches and gelatins, respectively, as the preferred fluids for septic shock. As the first choice of vasopressors in patients with sepsis, 727 (74.9%) anesthesiologists chose the correct answer (norepinephrine). Anesthesiologists from tertiary hospitals (class A) had greater familiarity and compliance with the SSC guidelines than those from other hospitals (P < 0.001). In summary, anesthesiologists in China have some knowledge of the SSC guidelines and tend to practice in keeping with these guidelines. However, for some items, anesthesiologists are not up to date with the latest version of the SSC guidelines. The popularity of these guidelines is not homogenous among different levels of hospital. Anesthesiologists must strengthen their knowledge of the SSC guidelines and update their practice in a regular and timely manner, especially in other tertiary and primary hospitals.

Association of Vasopressor Choice with Clinical and Functional Outcomes Following Moderate to Severe Traumatic Brain Injury: A TRACK-TBI Study.

Early hypotension following moderate to severe traumatic brain injury (TBI) is associated with increased mortality and poor long-term outcomes. Current guidelines suggest the use of intravenous vasopressors to support blood pressure following TBI; however, guidelines do not specify vasopressor type, resulting in variation in clinical practice. Minimal data are available to guide clinicians on optimal early vasopressor choice to support blood pressure following TBI. Therefore, we conducted a multicenter study to examine initial vasopressor choice for the support of blood pressure following TBI and its association with clinical and functional outcomes after injury. We conducted a retrospective cohort study of patients enrolled in the transforming research and clinical knowledge in traumatic brain injury (TRACK-TBI) study, an 18-center prospective cohort study of patients with TBI evaluated in participating level I trauma centers. We examined adults with moderate to severe TBI (defined as Glasgow Coma Scale score < 13) who were admitted to the intensive care unit and received an intravenous vasopressor within 48h of admission. The primary exposure was initial vasopressor choice (phenylephrine versus norepinephrine), and the primary outcome was 6-month Glasgow Outcomes Scale Extended (GOSE), with the following secondary outcomes: length of hospital stay, length of intensive care unit stay, in-hospital mortality, new requirement for dialysis, and 6-month Disability Rating Scale. Regression analysis was used to assess differences in outcomes between patients exposed to norepinephrine versus phenylephrine, with propensity weighting to address selection bias due to the nonrandom allocation of the treatment groups and patient dropout. The final study sample included 156 patients, of whom 79 (51%) received norepinephrine, 69 (44%) received phenylephrine, and 8 (5%) received an alternate drug as their initial vasopressor. 121 (77%) of patients were men, with a mean age of 43.1years. Of patients receiving norepinephrine as their initial vasopressor, 32% had a favorable outcome (GOSE 5-8), whereas 40% of patients receiving phenylephrine as their initial vasopressor had a favorable outcome. Compared with phenylephrine, exposure to norepinephrine was not significantly associated with improved 6-month GOSE (weighted odds ratio 1.40, 95% confidence interval 0.66-2.96, p = 0.37) or any secondary outcome. The majority of patients with moderate to severe TBI received either phenylephrine or norepinephrine as first-line agents for blood pressure support following brain injury. Initial choice of norepinephrine, compared with phenylephrine, was not associated with improved clinical or functional outcomes.

Vasopressor Therapy in Cardiac Surgery—An Experts’ Consensus Statement

Hemodynamic conditions with reduced systemic vascular resistance commonly are observed in patients undergoing cardiac surgery and may range from moderate reductions in vascular tone, as a side effect of general anesthetics, to a profound vasodilatory syndrome, often referred to as vasoplegic shock. Therapy with vasopressors is an important pillar in the treatment of these conditions. There is limited guidance on the appropriate choice of vasopressors to restore and optimize systemic vascular tone in patients undergoing cardiac surgery. A panel of experts in the field convened to develop statements and evidence-based recommendations on clinically relevant questions on the use of vasopressors in cardiac surgical patients, using a critical appraisal of the literature following the GRADE system and a modified Delphi process. The authors unanimously and strongly recommend the use of norepinephrine and/or vasopressin for restoration and maintenance of systemic perfusion pressure in cardiac surgical patients; despite that, the authors cannot recommend either of these drugs with respect to the risk of ischemic complications. The authors unanimously and strongly recommend against using dopamine for treating post-cardiac surgery vasoplegic shock and against using methylene blue for purposes other than a rescue therapy. The authors unanimously and weakly recommend that clinicians consider early addition of a second vasopressor (norepinephrine or vasopressin) if adequate vascular tone cannot be restored by a monotherapy with either norepinephrine or vasopressin and to consider using vasopressin as a first-line vasopressor or to add vasopressin to norepinephrine in cardiac surgical patients with pulmonary hypertension or right-sided heart dysfunction.

Vasopressor Therapy in the Intensive Care Unit

After fluid administration for vasodilatory shock, vasopressors are commonly infused. Causes of vasodilatory shock include septic shock, post-cardiovascular surgery, post-acute myocardial infarction, postsurgery, other causes of an intense systemic inflammatory response, and drug -associated anaphylaxis. Therapeutic vasopressors are hormones that activate receptors-adrenergic: α1, α2, β1, β2; angiotensin II: AG1, AG2; vasopressin: AVPR1a, AVPR1B, AVPR2; dopamine: DA1, DA2. Vasopressor choice and dose vary widely because of patient and physician practice heterogeneity. Vasopressor adverse effects are excessive vasoconstriction causing organ ischemia/infarction, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. To date, no randomized controlled trial (RCT) of vasopressors has shown a decreased 28-day mortality rate. There is a need for evidence regarding alternative vasopressors as first-line vasopressors. We emphasize that vasopressors should be administered simultaneously with fluid replacement to prevent and decrease duration of hypotension in shock with vasodilation. Norepinephrine is the first-choice vasopressor in septic and vasodilatory shock. Interventions that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality significantly. In patients not responsive to norepinephrine, vasopressin or epinephrine may be added. Angiotensin II may be useful for rapid resuscitation of profoundly hypotensive patients. Inotropic agent(s) (e.g., dobutamine) may be needed if vasopressors decrease ventricular contractility. Dopamine has fallen to almost no-use recommendation because of adverse effects; angiotensin II is available clinically; there are potent vasopressors with scant literature (e.g., methylene blue); and the novel V1a agonist selepressin missed on its pivotal RCT primary outcome. In pediatric septic shock, vasopressors, epinephrine, and norepinephrine are recommended equally because there is no clear evidence that supports the use of one vasoactive agent. Dopamine is recommended when epinephrine or norepinephrine is not available. New strategies include perhaps patients will be started on several vasopressors with complementary mechanisms of action, patients may be selected for particular vasopressors according to predictive biomarkers, and novel vasopressors may emerge with fewer adverse effects.

Vasopressor treatment and mortality following nontraumatic subarachnoid hemorrhage: a nationwide electronic health record analysis.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular condition, not only due to the effect of initial hemorrhage, but also due to the complication of delayed cerebral ischemia (DCI). While hypertension facilitated by vasopressors is often initiated to prevent DCI, which vasopressor is most effective in improving outcomes is not known. The objective of this study was to determine associations between initial vasopressor choice and mortality in patients with nontraumatic SAH. The authors conducted a retrospective cohort study using a large, national electronic medical record data set from 2000-2014 to identify patients with a new diagnosis of nontraumatic SAH (based on ICD-9 codes) who were treated with the vasopressors dopamine, phenylephrine, or norepinephrine. The relationship between the initial choice of vasopressor therapy and the primary outcome, which was defined as in-hospital death or discharge to hospice care, was examined. In total, 2634 patients were identified with nontraumatic SAH who were treated with a vasopressor. In this cohort, the average age was 56.5 years, 63.9% were female, and 36.5% of patients developed the primary outcome. The incidence of the primary outcome was higher in those initially treated with either norepinephrine (47.6%) or dopamine (50.6%) than with phenylephrine (24.5%). After adjusting for possible confounders using propensity score methods, the adjusted OR of the primary outcome was higher with dopamine (OR 2.19, 95% CI 1.70-2.81) and norepinephrine (OR 2.24, 95% CI 1.80-2.80) compared with phenylephrine. Sensitivity analyses using different variable selection procedures, causal inference models, and machine-learning methods confirmed the main findings. In patients with nontraumatic SAH, phenylephrine was significantly associated with reduced mortality in SAH patients compared to dopamine or norepinephrine. Prospective randomized clinical studies are warranted to confirm this finding.

Vasopressor therapy in critically ill patients with shock.

Vasopressors are administered to critically ill patients with vasodilatory shock not responsive to volume resuscitation, and less often in cardiogenic shock, and hypovolemic shock. The objectives are to review safety and efficacy of vasopressors, pathophysiology, agents that decrease vasopressor dose, predictive biomarkers, β1-blockers, and directions for research. The quality of evidence was evaluated using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Vasopressors bind adrenergic: α1, α2, β1, β2; vasopressin: AVPR1a, AVPR1B, AVPR2; angiotensin II: AG1, AG2; and dopamine: DA1, DA2 receptors inducing vasoconstriction. Vasopressor choice and dose vary because of patients and physician practice. Adverse effects include excessive vasoconstriction, organ ischemia, hyperglycemia, hyperlactatemia, tachycardia, and tachyarrhythmias. No randomized controlled trials of vasopressors showed a significant difference in 28-day mortality rate. Norepinephrine is the first-choice vasopressor in vasodilatory shock after adequate volume resuscitation. Some strategies that decrease norepinephrine dose (vasopressin, angiotensin II) have not decreased 28-day mortality while corticosteroids have decreased 28-day mortality significantly in some (two large trials) but not all trials. In norepinephrine-refractory patients, vasopressin or epinephrine may be added. A new vasopressor, angiotensin II, may be useful in profoundly hypotensive patients. Dobutamine may be added because vasopressors may decrease ventricular contractility. Dopamine is recommended only in bradycardic patients. There are potent vasopressors with limited evidence (e.g. methylene blue, metaraminol) and novel vasopressors in development (selepressin). Norepinephrine is first choice followed by vasopressin or epinephrine. Angiotensin II and dopamine have limited indications. In future, predictive biomarkers may guide vasopressor selection and novel vasopressors may emerge.

SYNTHETIC ANGIOTENSIN II EXACERBATION OF SEPTIC MYOCARDITIS, CAUTIOUS UTILIZATION OF NOVEL VASOPRESSOR PHARMACEUTICALS

Treatment of septic shock has become standardized nationwide. Patients who fail adequate fluid resuscitation require urgent treatment with vasopressors. Only recently has physician's choice of vasopressor expanded to incorporate synthetic Angiotensin II (SA2). A 33-year-old male was transferred for