Line Vasopressor Research Articles

Comparison Between Norepinephrine-Epinephrine and Norepinephrine-Vasopressin Effectiveness in Reducing Mortality in Septic Shock: A Systematic Review

<div class="page" title="Page 1"><div class="layoutArea"><div class="column"><p> </p><p><strong>Background: </strong>Sepsis is a state of organ dysfunction caused by the immune system’s abnormal response to an infection. Septic shock is sepsis complicated by circulatory and metabolic abnormalities, oftentimes resulting in death. Prompt identification and treatment of septic shock is crucial for the survival of patients. The latest international guideline recommends the administration of norepinephrine as the first line vasopressor, with the addition of epinephrine or vasopressin as an aid in achieving the target MAP (Mean Arterial Pressure).</p><p><strong>Methods: </strong>This study is a systematic review of literatures from the databases Pubmed PMC, Science Direct, and Proquest. Systematic reviews on septic shock, norepinephrine, and epinephrine or vasopressin were among the inclusion criterias. This resulted in a total of five systematic reviews to be included in the qualitative synthesis.</p><p><strong>Results: </strong>The five included studies were not in sync as to which vasopressor is best used for the treatment of septic shock patients. One of which did not compare the two combinations within the same category, two of which favored the use of norepinephrine-epinephrine, and the other two favored the use of norepinephrine-vasopressin for the treatment of septic shock patients.</p><p><strong>Conclusion: </strong>The existing evidence were insufficient to give a conclusion of the best combination of vasopressors for septic shock patients. More research, specifically randomized controlled trials, needs to be conducted on this topic with well defined administration of combinations of vasopressors as an advancement of this systematic review. The writers also recommend the delay of anymore systematic reviews until the former recommendation has been met.</p></div></div></div>

Up-dates on Cardio-Circulatory Support

In-hospital mortality rates have approved in the recent past1 6 to 12-month death persists at approximately 50%2. The goal of treatment is to reestablish tissue perfusion while closely monitoring hemodynamics. Provisional automatic cardiovascular support is a mainstay of the management of patients who cannot be stabilized with medical therapy. Apart from the acute setting, automatic cardiovascular support is also used in the mid- and long-term treatment of heart failure patients. This can either be until heart transplant or life-long in patents who are not candidates for heart transplant. Further it is an essential tool of open-heart surgery. In the present review we will give an overview and update of the different devices for mechanical cardiac support. Non-mechanical Cardio-Circulatory Support includes intravenous fluids and pharmacological treatment with vasopressors and inotropic agents. Norepinephrine is mainly a vasopressor, but also has other activities such as inotropy. It serves as first line agent, particularly in the acute setting of a cardiogenic shock. A recent randomized trial comparing Norepinephrine versus Epinephrine in cardiogenic shock after myocardial infarction found that Norepinephrine appeared to be a safer choice than Epinephrine3. Vasopressin causes less pulmonary vasoconstriction than norepinephrine and is therefore might better as a first line vasopressor compared to Norepinephrine4. Dobutamine, a beta agonist is frequently being used for cardiogenic shock, acting as inotropic agent. Levosimendan is a Calcium sensitizer and often used in patients with acute decompensation of chronic heart failure.

Norepinephrine versus phenylephrine for maintenance of blood pressure during spinal anaesthesia for caesarean delivery - A randomized double blind controlled study

: Currently phenylephrine is a preferred 1 line vasopressor for maintenance of blood pressure during spinal anaesthesia, may be associated with reflex bradycardia and decreased cardiac output, posing risk to mother or foetus. Norepinephrine may be an useful alternative as being potent alpha with weak beta adrenergic agonist activity. : This study compared the effectiveness of prophylactic and treatment boluses of norepinephrine and phenylephrine to maintain systolic blood pressure at or above 80% of baseline value during spinal anesthesia for cesarean delivery with the primary aim to compare cardiac output. Secondary aims were total doses of study drug required, neonatal outcome and perioperative complications.: Total 100, term pregnant women with ASA status II undergoing caesarean delivery under spinal anaesthesia were enrolled in this prospective, double blind controlled study. Patients were randomized to receive prophylactic bolus dose of norepinephrine (6 µg) or phenylephrine (100 µg) immediately after spinal anaesthesia. Systolic blood pressure, cardiac output and heart rate were monitored. Intermittent bolus doses were repeated whenever required. Student ‘t’ test and chi square test were used for analysing the data. : Both the drugs were able to maintain the systolic blood pressure ≥ 80% of baseline (p=0.356). Significant difference observed in cardiac output while comparing both the groups from 3 to 15 minutes after spinal anesthesia (p=0.014). The incidence of bradycardia was lower in norepinephrine group as compared to phenylephrine group (P=0.018). : Norepinephrine is as effective as phenylephrine for maintenance of blood pressure after spinal anaesthesia for caesarean delivery with stable heart rate and cardiac output.

Vasopressors in Septic Shock (A Systematic Review / Meta-Analysis)

Abstract Background sepsis is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. Septic shock occurs in a subset of patients with sepsis and comprises of an underlying circulatory and cellular/metabolic abnormality that is associated with increased mortality. Septic shock is defined by persisting hypotension requiring vasopressors to maintain a mean arterial pressure of 65 mm Hg or higher and a serum lactate level greater than 2 mmol/L (18 mg/dL) despite adequate volume resuscitation. Purpose to assess the role of Vasopressors in septic shock and compare the effects among different types of vasopressor drugs. Patients and Methods this meta-analysis study was done on 18 studies randomized controlled studies on adult patients ( at least 18 years of age ) with septic shock and had reported mortality outcome. The study compared five vasopressors EN, DA, VP, TP and PE with norepinephrine (NE) (the control drug) in efficacy and safety. Results with comparison of the five vasopressors to NE, Vasopressin and its long acting analogue Terlipressin proved to be the competiting agents to NE but not the replacement choices due to many limitations to the study. Conclusion norepinephrine remains the first choice vasopressor to treat patients with septic shock. The use of vasopressin or terlipressin as a first line vasopressor for the support of MAP is not recommended.

Current Practice of Calcium Use During Cardiopulmonary Bypass Weaning: Results of an International Survey

To describe international practices on the use of calcium salts during cardiopulmonary bypass (CPB) weaning in adult cardiac surgery patients. Multiple-choice survey on current practice of CPB weaning. Online survey using the SurveyMonkey platform. Departments of cardiac anesthesiology worldwide. None. Out of 112 surveys sent, 100 centers from 32 countries replied. The majority of centers (88 of 100 = 88%) administer calcium salts intraoperatively: 71 of 100 (71%) are using these drugs for CPB weaning and 78 of 100 (78%) for correction of hypocalcemia. Among the 88 centers that use calcium salts intraoperatively, 66% (58 of 88) of respondents use calcium chloride, 22% (19 of 88) use calcium gluconate, and 12% (11 of 88) use both drugs. Calcium salts are routinely used during normal (47 of 71 centers = 66%) and difficult (59 of 71 centers = 83%) weaning from CPB. Doses of 5 to 15 mg/kg during termination of CPB were used by 55 of 71 centers (77%) either by bolus (39 of 71, 55%) or over a time period longer than 1 minute (32 of 71 = 45%). Norepinephrine is the most commonly used first line vasopressor or inotropic agent used to support hemodynamics during termination of CPB in 32 out of 100 centers (32%), and calcium is the second one, used by 23 out of 100 centers (23%). This survey demonstrates that the majority of cardiac centers use calcium in adult patients undergoing cardiac surgery, especially during weaning from CPB. There is variability on the type of drug, dose, and modality of drug administration.

Vasopressors to treat refractory septic shock

Norepinephrine is the first line vasopressor used in patients with septic shock. However, norepinephrine doses above 1 µg/kg/min are associated with mortality rates of over 80%, suggesting a need to implement adjunctive strategies prior to reaching this dosage. The present study therefore sought to review the existing and emergent vasopressor agents for patients with refractory septic shock. This paper summarizes the use of vasoactive drugs that may be considered in the context of refractory shock. The clinical application of present and future therapies and the related outcome are discussed. A review of the available literature indicated that vasopressin may be a good first option in patients with refractory septic shock, but evidence remains somewhat sparse. Although the use of vasopressin in these circumstances is likely preferable to the use of terlipressin, a pro-drug with an extended half-life, the use of selepressin, a pure V1 agonist, should be further assessed in future studies. Angiotensin II is another emerging option that uses a different signaling pathway. However, nitric oxide synthase inhibitors and methylene blue do not appear to be appropriate in the management of patients with refractory septic shock. In conclusion, the use of different adjunctive agents in combination with the use of norepinephrine may be useful in patients with refractory septic shock, but care must be taken to avoid excessive vasoconstriction.

Optimal fluid management in sepsis

Sepsis clinically manifests as life-threatening organ dysfunction due to a dysregulated host response to infection.1 Optimal fluid resuscitation is relevant for all sepsis patients, and perhaps it is most important for those with septic shock. Septic shock is defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greatest risk of mortality, and septic shock is clinically identified as sepsis patients with serum lactate level >2 mmol/L and who require vasopressor infusion to maintain a mean arterial pressure ≥ 65 mm Hg in the absence of hypovolemia. Sepsis is among the most common conditions in the intensive care unit (ICU), accounting for up to half of all hospital deaths and being the third leading cause of death overall in the United States.2 Sepsis and septic shock are medical emergencies for which treatment and resuscitation should begin immediately. The goals of fluid resuscitation for these patients are: a) to rapidly replace intravascular volume and restore tissue perfusion, and b) to minimize organ dysfunction through timely interventions that either halt or reverse the physiologic derangements. If hypoperfusion is present, at least 30 mL/kg of IV crystalloid fluid should be given rapidly, and additional fluids should be guided by frequent reassessment of hemodynamic status, preferably using dynamic indices to indicate the likelihood of a beneficial response to fluid administration. Fluid administration should be targeted to achieve a MAP of at least 65 mm Hg, and to normalize lactate in patients with elevated lactate due to hypoperfusion.3 Balanced crystalloids are the fluid of first choice for sepsis resuscitation based on ready availability and taking medication costs into account. Use of 0.9% saline compared to a balanced crystalloid, such as lactated Ringer's or PlasmaLyte, produces more kidney dysfunction and with a greater risk of dying.4 The individual side effect profiles may best differentiate the natural and synthetic colloids. Albumin may be considered for administration to sepsis patients with refractory shock or who have received substantial amounts of crystalloid fluids, but should not be administered to patients with severe traumatic brain injury.5 Hydroxyethyl starch (HES) products should not be administered to patients with sepsis because of increased risk of acute kidney injury and death. Gelatin solutions are not recommended in sepsis.Norepinephrine is the vasopressor of first choice for patients with septic shock, and should be administered to achieve a mean arterial pressure of at least 65 mm Hg after excluding hypovolemia as a cause for hypotension. The selection of a second line vasopressor, such as vasopressin, dopamine, phenylephrine, epinephrine or angiotensin-2, depends on patient factors such as underlying cardiac dysfunction, presence of arrhythmias, and current response to vasoconstrictor or inotropic agents. Dopamine should not be used for renal perfusion or protection and it should be avoided in patients with tachyarrhythmias.

Self assessment questions

A 34-year-old lady is referred to ICU with suspected septic shock following a missed miscarriage at 17/40 gestation. Which of the following statements is true regarding the management of sepsis in pregnancy?A.The qSOFA score has been validated in the pregnant populationB.The UK maternal mortality rate for sepsis has increased between the 2009 and 2012 and 2013 and 2015 MBRRACE-UK reports.C.There is an increase in mortality for every hour that the administration of appropriate antibiotic therapy is delayed.D.Adrenaline is the first line vasopressor in the ICUE.Lactate is not a helpful indicator of the severity of maternal sepsis

Vasopressors for the Treatment of Septic Shock: Systematic Review and Meta-Analysis.

ObjectiveInternational guidelines recommend dopamine or norepinephrine as first-line vasopressor agents in septic shock. Phenylephrine, epinephrine, vasopressin and terlipressin are considered second-line agents. Our objective was to assess the evidence for the efficiency and safety of all vasopressors in septic shock.MethodsSystematic review and meta-analysis. We searched electronic database of MEDLINE, CENTRAL, LILACS and conference proceedings up to June 2014. We included randomized controlled trials comparing different vasopressors for the treatment of adult patients with septic shock. Primary outcome was all-cause mortality. Other clinical and hemodynamic measurements were extracted as secondary outcomes. Risk ratios (RR) and mean differences with 95% confidence intervals (CI) were pooled.ResultsThirty-two trials (3,544 patients) were included. Compared to dopamine (866 patients, 450 events), norepinephrine (832 patients, 376 events) was associated with decreased all-cause mortality, RR 0.89 (95% CI 0.81-0.98), corresponding to an absolute risk reduction of 11% and number needed to treat of 9. Norepinephrine was associated with lower risk for major adverse events and cardiac arrhythmias compared to dopamine. No other mortality benefit was demonstrated for the comparisons of norepinephrine to epinephrine, phenylephrine and vasopressin / terlipressin. Hemodynamic data were similar between the different vasopressors, with some advantage for norepinephrine in central venous pressure, urinary output and blood lactate levels.ConclusionsEvidence suggests a survival benefit, better hemodynamic profile and reduced adverse events rate for norepinephrine over dopamine. Norepinephrine should be regarded as the first line vasopressor in the treatment of septic shock.

The Heart in Sepsis: From Basic Mechanisms to Clinical Management

Septic shock is characterized by circulatory compromise, microcirculatory alterations and mitochondrial damage, which all reduce cellular energy production. In order to reduce the risk of major cell death and a diminished likelihood of recovery, adaptive changes appear to be activated. As a result, cells and organs may survive in a non-functioning hibernation-like condition. Sepsis-induced cardiac dysfunction may represent an example of such functional shutdown. Sepsis-induced myocardial dysfunction is common, corresponds to the severity of sepsis, and is reversible in survivors. Its mechanisms include the attenuation of the adrenergic response at the cardiomyocyte level, alterations of intracellular calcium trafficking and blunted calcium sensitivity of contractile proteins. All these changes are mediated by cytokines. Treatment includes preload optimization with sufficient fluids. However, excessive volume loading is harmful. The first line vasopressor recommended at present is norepinephrine, while vasopressin can be started as a salvage therapy for those not responding to catecholamines. During early sepsis, cardiac output can be increased by dobutamine. While early administration of catecholamines might be necessary to restore adequate organ perfusion, prolonged administration might be harmful. Novel therapies for sepsis-induced cardiac dysfunction are discussed in this article. Cardiac inotropy can be increased by levosimendan, istaroxime or omecamtiv mecarbil without greatly increasing cellular oxygen demands. Heart rate reduction with ivabradine reduces myocardial oxygen expenditure and ameliorates diastolic filling. Beta-blockers additionally reduce local and systemic inflammation. Advances may also come from metabolic interventions such as pyruvate, succinate or high dose insulin substitutions. All these potentially advantageous concepts require rigorous testing before implementation in routine clinical practice.

62

Introduction: The non-selective vasopressin agonist, arginine vasopressin (AVP) is widely used as second line vasopressor in septic shock patients as add-on to norepinephrine (NE). However, animal septic shock studies have shown selective V1a receptor agonists to be superior to AVP in alleviating organ dysfunction. Selepressin (FE 202158) is the first selective V1a agonist to be evaluated in septic shock patients. Hypothesis: Selepressin reduces NE requirements and duration of organ dysfunction in human septic shock. Methods: In a randomized double-blind, placebo controlled trial, septic shock patients in need of vasopressor support (?0.1 µg/kg/min NE for?2h) received selepressin (1.25 ng/kg/min (n=10) or 2.5 ng/kg/min (n=19) or placebo (n=21) until shock resolution or for up to 7 days. If target mean arterial pressure (MAP) of 65 mmHg could not be achieved, open-label NE was added. The co-primary endpoints were ability to maintain target MAP without NE, NE infusion rate and cumulative dose of NE. Secondary endpoints included organ dysfunction and fluid balance. Results: Selepressin dose-dependently reduced the 7-day cumulative dose of open-label NE (placebo: 772 µg/kg, 1.25 ng/kg/min selepressin: 617 µg/kg and 2.5 ng/kg/min selepressin: 249 µg/kg, p=0.007). NE was weaned more rapidly in the selepressin group: 2.5 ng/kg/min selepressin increased the proportion of patients maintaining target MAP without open-label NE compared to placebo (69% vs. 20%, p=0.005) and reduced mean NE infusion rate (0.04 vs. 0.18, p=0.0001) in the first 24h following initiation of study drug. Interestingly, the 2.5 ng/kg/min selepressin group had faster recovery than placebo as shown by a higher proportion of patients out of shock at 48h (57.9 vs. 28.6%, p=0.1) and higher proportion of days alive and free of ventilation within the first 7 days (53.8 vs. 23.1%, p=0.01) in spite of similar baseline NE requirements and SOFA score. Moreover, 7-day cumulative fluid balance was lower in the 2.5 ng/kg/min selepressin group than in placebo (9.0 vs. 6.5 L, p=0.1). Conclusions: Selepressin dose-dependently reduced NE requirements, as well as the need for mechanical ventilation, and appeared to shorten time to shock resolution in septic shock patients.

Prevention of Hypotension following Spinal Anaesthesia in Caesarean Section - then and now

Hypotension during spinal anaesthesia for caesarean section remains a common scenario in our clinical practice. Certain risk factors play a role in altering the incidence of hypotension. Aortocaval compression counteraction does not help to prevent hypotension. Intravenous crystalloid prehydration has poor efficacy; thus, the focus has changed toward co-hydration and use of colloids. Phenylephrine is established as a firstline vasopressor, although there are limited data from high-risk patients. Ephedrine crosses the placenta more than phenylephrine and cause possible alterations in the foetal physiology.

Vasopressin and Terlipressin in the Treatment of Vasodilatory Septic Shock: A Systematic Review

Background: Vasodilatory septic shock unresponsive to fluid resuscitation requires the addition of vasopressors. Catecholamines remain the first line vasopressor therapy, but treatment failure is a potential problem. Vasopressin and its analogue, terlipressin, have been used for this indication. Objective: This systematic review aims to evaluate the effects of vasopressin and terlipressin on mortality and morbidity outcomes in patients with vasodilatory shock. Secondary outcomes include the effects of vasopressin and terlipressin on haemodynamic stability and organ function. Method: A computerised search of MEDLINE from January 1966 till June 2010 and screening of references of relevant articles were conducted. Only prospective, randomised controlled trials comparing vasopressin or terlipressin versus standard vasopressors or placebo were included. Results: Seven studies using vasopressin, three using terlipressin and one using both were identified. Four vasopressin trials assessing mortality and morbidity outcomes showed a trend towards benefit for mortality in adults but possibly adverse outcomes in a small paediatric study. No data was available on the long-term mortality and morbidity outcomes of terlipressin. Vasopressin and terlipressin were similar to standard vasopressors in maintaining haemodynamic parameters, while allowing a beneficial catecholamine-sparing effect. These agents also had a neutral to positive effect on organ function. Conclusion: Vasopressin and terlipressin was comparable to conventional agents in the maintenance of haemodynamic stability and organ function in vasodilatory shock. Since morbidity and mortality data do not differentiate vasopressin and terlipressin from catecholamines, their role remains unclear. More large studies evaluating the long-term outcomes in this group of patients are required.