Use Of Vasopressor Agents Research Articles

Cardiorespiratory interaction: a novel mechanical approach to treating intraoperative hypotension.

This Invited Commentary accompanies the following original article: Birch M, Kwon Y, Loushin MK, et al. Intrathoracic pressure regulation to treat intraoperative hypotension. A phase II pilot study. Eur J Anaesthesiol 2015; 32:376–380. A consensus definition of intraoperative hypotension (IOH) remains to be achieved,1 though commonly used definitions include a reduction in SBP below 80 mmHg and an episode of SBP more than 20% below baseline or normal for the patient. Without an agreed definition, the true incidence is difficult to estimate, but IOH is common and occurs in between 5 and 99% of patients undergoing anaesthesia.1 Despite the lack of a consensus definition, it is clear that IOH can harm patients. Reduction of the mean arterial pressure below 55 mmHg, for as little as 1 to 5 min, can carry a significantly increased risk of acute postoperative kidney injury and myocardial ischaemia.2 In addition, IOH has been associated with peri-operative stroke.3 It has a negative influence on outcomes not only in the immediate postoperative period but also up to 1 year after surgery.4 What is unclear from the outcome studies of IOH is why harm occurs. Brady and Hogue4 suggest that adverse events could be due to the use of vasopressor agents in the treatment of IOH rather than the hypotension itself. In this issue of the Journal, Birch et al.5 offer a novel, nonpharmacological treatment for IOH. Here, an intrathoracic pressure regulation device is attached to the endotracheal tube to reduce intrathoracic pressure throughout the respiratory cycle. The authors hypothesise that the device works by reducing intrathoracic pressure and increasing venous return to the heart, leading to the correction of hypotension. This device reduces the increase in intrathoracic pressure associated with positive pressure ventilation and exerts negative transpulmonary pressure during the expiratory phase. Although the intrathoracic pressure regulation device may appear to offer an innovative solution to IOH, there are a number of issues that require further investigation. Firstly, the device requires the use of positive pressure ventilation without positive end-expiratory pressure (PEEP). Although the correct level of PEEP during surgery is yet to be established,6 application of PEEP appears to be important. Lack of PEEP during general anaesthesia results in ventilator-induced lung injury and has been associated with an increase in mortality.7,8 The authors report that atelectasis and airway de-recruitment events were not observed during the trial. However, the number of patients (n = 17) was too small to detect the likely adverse event rate, and because this was only a pilot study, there was no control group. The authors state that there were no changes in pulse oximetry measurements during the trial, but they report only the mean fraction of inspired oxygen for the whole patient cohort, making detection of desaturation events difficult. Secondly, application of the device requires an increase in gas flow through the anaesthetic machine. This reduces efficiency in the use of volatile anaesthetics with low flow systems and therefore increases gas scavenging requirements and costs. Finally, reversal of IOH occurred at a mean of 8 min after applying the intrathoracic pressure regulation device. This period is in excess of that shown to be potentially harmful (<5 min) and slower than the correction of IOH that would be expected with vasopressor agents. Intrathoracic pressure regulation offers an interesting and novel mechanical approach to the management of IOH. Birch et al.5 raise a number of important issues relating to the management of IOH and application of the intrathoracic pressure regulation device, which can only be answered by further well conducted randomised controlled trials. Acknowledgements relating to this article Assistance with the commentary: none. Financial support and sponsorship: none. Conflicts of interest: none. Comment from the editor: this invited commentary was checked and accepted by the editors but was not sent for external peer review. MC is an associate editor of the Eur J Anaesthesiol.

Pharmacist input into statewide treatment protocols for emergency medical services.

A pharmacist's role in helping Vermont health officials standardize pharmacotherapy-related protocols used by emergency medical services (EMS) personnel across the state is described. Pharmacists with expertise in emergency medicine (EM) or critical care are ideally positioned to provide guidance on optimizing and standardizing medication-use aspects of state and local EMS protocols. In 2012, the medical director of the EMS division of the Vermont Department of Health requested that an EM pharmacist at a Burlington academic medical center review draft EMS protocols designed to replace the existing patchwork of local protocols with statewide standards of care; among the 92 draft protocols reviewed, 62 pertained to medication use. The pharmacist provided a wide range of suggestions on 33 protocols, including (1) evidence-based recommendations on use of vasopressor agents for septic shock, (2) recommendations to optimize medication ordering and preparation in the prehospital setting, (3) recommendations on prehospital management of pediatric shock and appropriate use of chemical restraints, and (4) recommendations to promote use of smart infusion pumps by EMS personnel. All of the pharmacist's suggestions were incorporated into the final protocols, which took effect in March 2014. The protocols have helped standardize care for patients receiving EMS services throughout Vermont while reducing the potential for medication errors. An EM pharmacist participated in the review and development of statewide EMS treatment protocols that focused on choice of medication therapy, dosage, administration, and identification and minimization of potential risks of medication errors.

Let's change our behaviors: From bed rest and heavy sedation to awake, spontaneously breathing and early mobilized Intensive Care Unit patients.

Let's change our behaviors: From bed rest and heavy sedation to awake, spontaneously breathing and early mobilized Intensive Care Unit patients.

Accuracy of Determining Hemoglobin Level Using Occlusion Spectroscopy in Patients with Severe Gastrointestinal Bleeding

In patients presenting with severe hemorrhage, the authors conducted an equivalence trial that compared noninvasive occlusion spectroscopy and the capillary blood method to determine hemoglobin level. This prospective observational study included patients admitted to their intensive care unit for gastrointestinal bleeding. A ring-shaped sensor, connected to a NBM-200MP (OrSense, Nes Ziona, Israel), was fitted onto the patient's thumb to intermittently measure hemoglobin (SotHb). During the first 24 h after admission, venous hemoglobin level, considered as the reference method, was determined at the laboratory every 8 h and was compared to SotHb and the capillary blood method. The primary endpoint was the proportion of inaccurate measurements, defined as greater than 15% difference compared with reference values or their unavailability for any technical reason. The study was scheduled to include 68 patients but was stopped prematurely after an interim analysis of 34 patients. The proportion of inaccuracies revealed that SotHb could not be considered equivalent to the capillary blood method (47% [95% CI, 43-51] and 24% [95% CI, 20-28]). Considering venous hemoglobin level as a reference method, the mean biases for SotHb (n = 133) and the capillary blood method (n = 135) were, respectively, -0.4 ± 2.0 and 0.8 ± 1.2 g/dl (P < 0.05). SotHb was associated with an increased incidence of failed transfusion. The inaccuracy of SotHb tended to be increased in patients receiving vasopressor agents. Noninvasive determination of hemoglobin level based on occlusion spectroscopy lacks accuracy in patients presenting with severe gastrointestinal bleeding and cannot be considered equivalent to the capillary-based method. This inaccuracy seems to be moderately influenced by the infusion of vasopressor agents.

Effect of N-acetylcysteine treatment on oxidative stress and inflammation after severe burn

Oxidative stress and inflammation generate edema in burns. The aim of our study was to assess effect of N-acetylcysteine (NAC) on oxidative stress, inflammation, fluid requirement, multiple organ dysfunction (MOD) score and vasoactive drug requirement.In this study 15 patients were on standard therapy, whereas for other 15 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Levels of malondialdehyde, protein sulfhydril (PSH) groups, reduced gluthation (GSH), activity of myeloperoxidase, catalase and superoxide dismutase enzymes and induced free radical generating capacity were measured as well as concentrations of TNF-α, IL-6, IL-8, and IL-10. MOD score, use of vasopressor agents and fluid utilisation were recorded daily.NAC treatment increased GSH level on days 4–5 (p<0.05) and PSH level on days 2–6 (p<0.05) compared to controls. Plasma IL-6 was lower on days 4–5 (p<0.05), IL-8 on days 4–6 (p<0.05) and IL-10 on days 4–6 (p<0.05) in NAC group. NAC group received less catecholamines than controls (p<0.01) from day 4 without significant differences in MOD score.NAC treatment is associated with a diminished oxidative stress reflected in preserved antioxidant levels, lower inflammation mirrored in lower interleukin levels and less vasopressor requirement.

Effect of N-acetylcysteine treatment on the expression of leukocyte surface markers after burn injury

Oxidative stress and inflammatory processes generate edema in burns. Treatment of consequent hypovolemia is a challenge. The aim of study was to assess if glutathione pro-drug N-acetylcysteine (NAC) can influence inflammation and fluid requirement. We also aimed to compare organ functions scores and vasoactive drug requirement. This prospective randomised study involved 28 patients with burn injury affecting more than 20% of body surface area. Fourteen patients were on standard therapy, whereas for other 14 patients NAC was supplemented. Blood samples were taken on admission and on the next five consecutive mornings. Leukocyte surface marker expressions were determined, multiple organ function scores, use of vasopressor agents and fluid requirements were recorded daily. Expression of CD11a ( p < 0.05), CD18 ( p < 0.05) and CD97 ( p < 0.01) on the granulocytes were significantly lower in the NAC treated group, similarly to lymphocyte CD 49d ( p < 0.05) and monocyte CD 49d ( p < 0.01) and CD 97 ( p < 0.05) expression. No significant difference was found in the fluid requirement between groups but patients the NAC group required less vasopressor and inotropic drugs from day 4. NAC treatment is associated with a less pronounced inflammation reflected in lower CD marker expression and vasopressor requirement.

Optimization of Donor Management Goals Yields Increased Organ Use

Multiple strategies have been used in an effort to increase the pool of organs for transplantation. Standardizing donor management has produced promising results. Donor management goals (DMGs) are now being used as end points of intensive care unit care during the prerecovery phase but no prospective results have been reported. Data from the United Network for Organ Sharing Region 11 were collected for successful achievement of eight common donor management goals (mean airway pressure [MAP], central venous pressure [CVP], pH, PaO2, sodium, glucose, single pressor use, and urine output) before organ recovery. Two time periods were studied with different panels of DMGs. The analysis identified the success rate of transplantation. Goals were stratified by their statistical correlation with the number of organs transplanted per donor (OTPD) in an effort to identify the most important parameter(s). Eight hundred five organ donors were studied with 2685 organs transplanted. DMGs were assessed through two phases of the study. Achieving DMGs rose from 18 to 66 per cent associated with significant improvement in OTPD (range, 2.96 to 3.45). The success of transplantation was primarily associated with limitations in vasopressor use and PaO2. Tight glucose control did affect the rate of pancreatic transplants. Thoracic organs were the most sensitive to DMGs with a 10- to 15-fold increase in lung transplantation when PaO2 rose above 100 mmHg. MAP, CVP, pH, sodium, and urine output had little effect on transplantation. Standardization of end points of donor management was associated with increased rates of transplantation. Surprisingly, not all standard goals are necessary for optimal organ use. The most significant parameters were the low use of vasopressor agents and oxygenation. Donor management strategies should strive to optimize these goals.

β-Blockers for Chest Pain Associated With Recent Cocaine Use

Although beta-blockers prevent adverse events after myocardial infarction, they are contraindicated when chest pain is associated with recent cocaine use. Recommendations against this use of beta-blockers are based on animal studies, small human experiments, and anecdote. We sought to test the hypothesis that beta-blockers are safe in this setting. We performed a retrospective cohort study of consecutive patients admitted to the San Francisco General Hospital, San Francisco, California, with chest pain and urine toxicologic test results positive for cocaine, from January 2001 to December 2006. Mortality data were collected from the National Death Index. Of 331 patients with chest pain in the setting of recent cocaine use, 151 (46%) received a beta-blocker in the emergency department. There were no meaningful differences in electrocardiographic changes, troponin levels, length of stay, use of vasopressor agents, intubation, ventricular tachycardia or ventricular fibrillation, or death between those who did and did not receive a beta-blocker. After adjusting for potential confounders, systolic blood pressure significantly decreased a mean 8.6 mm Hg (95% confidence interval, 14.7-2.5 mm Hg) in those receiving a beta-blocker in the emergency department compared with those who received their first beta-blocker in the hospital ward (P = .006). Over a median follow-up of 972 days (interquartile range, 555-1490 days), after adjusting for potential confounders, patients discharged on a beta-blocker regimen exhibited a significant reduction in cardiovascular death (hazard ratio, 0.29; 95% confidence interval, 0.09-0.98) (P = .047). beta-Blockers do not appear to be associated with adverse events in patients with chest pain with recent cocaine use.

Vasopressor use in septic shock: an update

This article reviews new findings on the use of vasopressor agents in septic shock. Several recent large randomized clinical trials have compared vasopressor agents in patients with septic shock. Briefly, the survival of patients treated with norepinephrine alone or a combination of norepinephrine and dobutamine did not significantly differ from that of patients treated with epinephrine. In observational studies, dopamine use was associated with poor outcome. The results of a clinical trial comparing dopamine and norepinephrine as a first-line agent in septic shock are pending. The addition of low-dose vasopressin to norepinephrine did not significantly improve the survival of patients with septic shock. A positive effect on survival was observed in a predetermined (norepinephrine dose <15 microg/kg/min) subgroup of patients with moderate shock. There is no large randomized clinical trial on the use of terlipressin. In contrast, nitric oxide inhibitors were associated with increased mortality in patients with septic shock. The use of norepinephrine or epinephrine can be left to the discretion of the treating physician. Low-dose vasopressin administration remains an option for catecholamine-refractory septic shock. The potential benefit of early use in combination with a moderate dose of norepinephrine remains to be determined.

Management of Uncontrolled Hemorrhagic Shock

Management of Uncontrolled Hemorrhagic Shock

Hemodynamic optimization of sepsis-induced tissue hypoperfusion

Sepsis is associated with cardiovascular changes that may lead to development of tissue hypoperfusion. Early recognition of sepsis and tissue hypoperfusion is critical to implement appropriate hemodynamic support and prevent irreversible organ damage. End points for resuscitation need to be defined and invasive hemodynamic monitoring is usually required. Targets for hemodynamic optimization should include intravascular volume, blood pressure, and cardiac output. Therapeutic interventions aimed at optimizing hemodynamics in patients with sepsis include aggressive fluid resuscitation, the use of vasopressor agents, inotropic agents and in selected cases transfusions of blood products. This review will cover the most important aspects of hemodynamic optimization for treatment of sepsis induced tissue-hypoperfusion.

Anaesthesia for total hip replacement in a patient with Holt-Oram syndrome

Anaesthesia for total hip replacement in a patient with Holt-Oram syndrome

Use of vasopressor agents in critically ill patients.

Distributive shock is a common problem in intensive care. Systemic hypotension is a medical emergency and will cause end-organ injury if not reversed. There are relatively few medications available to treat distributive shock. Catecholamines are most widely used for this indication and work by stimulating alpha- and/or beta-adrenergic receptors. Vasopressin and corticosteroids may have a role in reversing refractory shock and work primary through nonadrenergic mechanisms. Shock is difficult to define using hemodynamic criteria, because the same hemodynamic values can be normal in one patient, yet represent shock in another. Thus, the appropriate therapeutic endpoints for vasopressor therapy are not uniform for all patients. Similarly, the available evidence comparing vasopressor agents in terms of safety and efficacy is limited. When used at doses necessary to reverse distributive shock, less potent vasoconstrictors (eg, dopamine) do not appear to be safer than more potent ones (eg, norepinephrine) and do not appear to be as effective.

Does a visual analogue colour chart carried by the retrieval team help in assessment of the fat content of donor livers?

Improved surgical techniques and better organ preservation [Z, 71 have resulted in a reduction in the incidence of primary nonfunction (PNF) following orthotopic liver transplantation [3]. However, the Occurrence of this devastating complication remains considerably higher in livers that exhibit histopathological evidence of macrovesicular steatosis (fatty liver). The recipients of such livers have an increase in morbidity and mortality [3,8]. Unfortunately, because of the continuing shortage of donor organs, there is now a prolonged recipient “waiting time” and a growing waiting list mortality rate. As a result, several transplant centres have resorted to using “fatty livers” for elective transplantation. Because the function of these “marginal livers” is difficult to predict prior to transplantation, various methods have been evaluated to assess their suitability for transplantation [6]. Donor risk factors, such as prolonged ICU stay, excessive use of vasopressor agents, increased bilirubin and excessive cold ischaemic times can all be a decision has to be made on whether an organ is transplantable and has resulted in a number of livers being used or discarded inappropriately. We attempted to standardise the assessment of the donor liver at harvesting with the aid of a visual analogue colour chart carried by the retrieval team. We prospectively evaluated 50 liver donors to assess the reliability of this approach. The visual analogue score recorded by the retrieving surgeon was compared both with the clinical outcome following implantation and with the histological assessment of the liver biopsy obtained before and after perfusion of the graft. This was examined using image analysis methodology. The Newcastle Ethical Committee has been approached for ethical approval, and consent to the study was obtained from all United Kingdom liver transplant centres.

Changing use of intensive care for hematological patients: the example of multiple myeloma.

Intensivists generally view patients with hematological malignancies as poor candidates for intensive care. Nevertheless, hematologists have recently developed more aggressive treatment protocols capable of achieving prolonged complete remissions in many of these patients. This change mandates a reappraisal of indications for ICU admission in each type of hematological disease. Improved knowledge of the prognosis is of assistance in making treatment decisions. The records of 75 myeloma patients consecutively admitted to our ICU between 1992 and 1998 were reviewed retrospectively and predictors of 30-day mortality were identified using stepwise logistic regression. The median age was 56 years (37-84). Chronic health status (Knaus scale) was C or D in 39 cases. Fifty-five patients (73%) had stage III disease and 17 had a complete or partial remission. Autologous bone marrow transplantation had been performed in 28 patients (37%). ICU admission occurred between 1992 and 1995 in 41 patients (54.7%), and between 1996 and 1998 in 34 patients (45.3%). The median SAPS II and LOD scores were 60 (23-107) and 7 (0-21), respectively. Reasons for ICU admission were acute respiratory failure in 39 patients (52%) and shock in 31 (41%). Forty-six patients (61%) required mechanical ventilation. Fifty patients (66%) received vasopressors and 24 dialysis. Thirty-day mortality was 57%. Only five parameters were independently associated with 30-day mortality in the multivariate model: female gender (OR = 5.12), mechanical ventilation (OR = 16.7) and use of vasopressor agents (OR = 5.67) were associated with a higher mortality rate, whereas disease remission (OR = 0.16) and ICU admission between 1996 and 1998 (OR = 0.09) were associated with a lower one. The prognosis for myeloma patients in the ICU is improving over time. This may reflect either recent therapeutic changes in hematological departments and ICUs or changes in patient selection for ICU admission. Hematologists and intensivists should work closely together to select hematological patients likely to benefit from ICU admission.

Inadequate Antimicrobial Treatment of Infections: A Risk Factor for Hospital Mortality Among Critically Ill Patients

To evaluate the relationship between inadequate antimicrobial treatment of infections (both community-acquired and nosocomial infections) and hospital mortality for patients requiring ICU admission. Prospective cohort study. Barnes-Jewish Hospital, a university-affiliated urban teaching hospital. Two thousand consecutive patients requiring admission to the medical or surgical ICU. Prospective patient surveillance and data collection. One hundred sixty-nine (8.5%) infected patients received inadequate antimicrobial treatment of their infections. This represented 25.8% of the 655 patients assessed to have either community-acquired or nosocomial infections. The occurrence of inadequate antimicrobial treatment of infection was most common among patients with nosocomial infections, which developed after treatment of a community-acquired infection (45.2%), followed by patients with nosocomial infections alone (34.3%) and patients with community-acquired infections alone (17.1%) (p < 0.001). Multiple logistic regression analysis, using only the cohort of infected patients (n = 655), demonstrated that the prior administration of antibiotics (adjusted odds ratio [OR], 3.39; 95% confidence interval [CI], 2.88 to 4.23; p < 0.001), presence of a bloodstream infection (adjusted OR, 1.88; 95% CI, 1.52 to 2.32; p = 0.003), increasing acute physiology and chronic health evaluation (APACHE) II scores (adjusted OR, 1.04; 95% CI, 1.03 to 1.05; p = 0.002), and decreasing patient age (adjusted OR, 1.01; 95% CI, 1.01 to 1.02; p = 0.012) were independently associated with the administration of inadequate antimicrobial treatment. The hospital mortality rate of infected patients receiving inadequate antimicrobial treatment (52.1%) was statistically greater than the hospital mortality rate of the remaining patients in the cohort (n = 1,831) without this risk factor (12.2%) (relative risk [RR], 4.26; 95% CI, 3.52 to 5.15; p < 0.001). Similarly, the infection-related mortality rate for infected patients receiving inadequate antimicrobial treatment (42.0%) was significantly greater than the infection-related mortality rate of infected patients receiving adequate antimicrobial treatment (17.7%) (RR, 2.37; 95% CI, 1.83 to 3.08; p < 0.001). Using a logistic regression model, inadequate antimicrobial treatment of infection was found to be the most important independent determinant of hospital mortality for the entire patient cohort (adjusted OR, 4.27; 95% CI, 3.35 to 5.44; p < 0.001). The other identified independent determinants of hospital mortality included the number of acquired organ system derangements, use of vasopressor agents, the presence of an underlying malignancy, increasing APACHE II scores, increasing age, and having a nonsurgical diagnosis at the time of ICU admission. Inadequate treatment of infections among patients requiring ICU admission appears to be an important determinant of hospital mortality. These data suggest that clinical efforts aimed at reducing the occurrence of inadequate antimicrobial treatment could improve the outcomes of critically ill patients. Additionally, prior antimicrobial therapy should be recognized as an important risk factor for the administration of inadequate antimicrobial treatment among ICU patients with clinically suspected infections.

The role of vasopressors in the management of hypotension induced by spinal and epidural anaesthesia

Although spinal and epidural blocks provide excellent anaesthesia for many operations, they are frequently accompanied by hypotension. This is largely the result of sympathetic nerve blockade. Excessive hypotension may potentially produce myocardial and cerebral ischaemia, and is associated with neonatal acidaemia in obstetric practice. How to prevent and treat this hypotension has been the subject of much investigation and controversy. One of the mainstays of management is the use of vasopressor agents and those currently available are not perfect. In this review, the role of vasopressor agents is discussed and possible future management strategies are commented upon. Ephedrine was the first agent used for this purpose and it has withstood the test of time: it is the agent against which all others are compared. It remains the first-line agent in obstetric anaesthesia as it does not affect the fetus adversely, but it cannot be relied upon to be 100% successful and other agents must be considered when it is inadequate. It is best given by infusion. In non-obstetric practice, ephedrine has a good track record but again its success rate is less than 100%. As there is no fetus to consider, it may be more appropriate to consider using a pure vasoconstrictor agent such as methoxamine or phenylephrine as a first-line therapy in such cases. This judgment can only be made on an individual patient basis as ephedrine produces a tachycardia while phenylephrine and methoxamine both produce bradycardia.

Vasopressor Agents in Shock

These authors discuss what to consider when vasopressors seem indicated and what factors to use in evaluating their efficacy.

Vasopressor Agents in Shock

Critical hemodynamic changes that are observed with the reduction of blood pressure in shock and the use of vasopressor agents as a temporary measure for maintaining arterial pressure so that irreparable tissue damage can be prevented are considered in this review of the use and efficacy of vasopressor agents in shock. Indications for adrenergic stimulators include severe hypotensive episodes, in which case an alpha-beta stimulator such as metaraminol or norepinephrine is the therapy of choice; hemorrhagic shock, in which administration of an alpha-beta stimulator will help maintain essential cerebral and cardiac function by shunting blood to these areas while volume is being replaced; cardiogenic shock, in which vasodilators may reduce cardiac work by reducing diastolic blood pressure but coronary blood flow will also be reduced, counteracting the effects of decreasing the cardiac load; and endotoxic shock, in which the circulating blood volume decreases and venous return and cardiac output also decrease. Prolonged use of these agents in any of these shock situations is ultimately deleterious. Vasopressor drugs are best used to treat acute hypotension that occurs in myocardial infarction; in such cses, vasopressors are used to keep the blood pressure within normal range, but only as adjunctive therapy. In hemorrhagic shock, though norepinephrine administration may increase blood pressure, the only lasting treatment is to replace the blood as rapidly as possible.

Experimental basis for the avoidance of vasopressors during heart block

Experiments in the anesthetized dog indicate that: 1. 1. Sudden reduction in heart rate from 142 to 44 per minute causes a rise in systemic vascular resistance and left atrial pressure. 2. 2. Infusion of a pressor agent with heart rate held constant at 142 per minute causes a rise in systemic vascular resistance and left atrial pressure. 3. 3. When the bradycardia and pressor infusion are combined, the rise in systemic vascular resistance and left atrial pressure is magnified. 4. 4. The use of vasopressor agents in patients with acute bradycardia appears hazardous.