Vasopressors for hypotensive shock

Gamper, Gunnar; Havel, Christof; Arrich, Jasmin; Losert, Heidrun; Pace, Nathan L.; Müllner, Marcus; Herkner, Harald

doi:10.1002/14651858.cd003709.pub4

Cited by 138 publications

(104 citation statements)

References 93 publications

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“…Clinicians have a menu of several vasopressors (e.g., norepinephrine, dopamine, epinephrine, terlipressin, vasopressin, and phenylephrine) for resuscitation of septic shock A recent, very comprehensive meta-analysis [51] evaluated the effects of different vasopressor drugs and regimens (alone or in combination) in patients admitted to ICU with hypotensive shock. Five vasopressors (dopamine, epinephrine, terlipressin, vasopressin, and phenylephrine) were compared with norepinephrine with respect to in-hospital, ICU, and 1-year mortality rates.…”

Section: Vasopressorsmentioning

confidence: 99%

Update of Sepsis in the Intensive Care Unit

Genga¹,

Russell²

2017

J Innate Immun

116

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Sepsis, the most common cause of admission to an intensive care unit (ICU), has had an increased incidence and prevalence over the last years with a simultaneous decrease in its short-term mortality. Sepsis survivors are more frequently discharged from hospital and often experience long-term outcomes such as late mortality, immune dysfunction, secondary infections, impaired quality of life, and unplanned readmissions. Early recognition and management of sepsis have challenged emergency care and critical care physicians and nurses. New sepsis definitions were produced and the Surviving Sepsis Campaign (SSC) 2016 was updated recently. Although hospital readmissions after sepsis are common, associated risk factors and how to manage patients who survive an episode of sepsis still need clarification. The immune dysfunction caused by sepsis/septic shock is complex, persistent, affects inflammatory and anti-inflammatory systems, and might be associated with long-term outcomes of sepsis. Several randomized controlled trials (RCT) that analyzed new (and old) interventions in sepsis/septic shock are discussed in this review in parallel with the SSC 2016 recommendations and other guidelines when relevant. RCTs addressing incidence, treatment, and prevention of important sepsis-associated organ dysfunction such as the acute respiratory distress syndrome, acute kidney injury, and brain dysfunction are highlighted. Finally, we briefly discuss the need for novel targets, predictive biomarkers, and new designs of RCTs in sepsis.

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Section: Vasopressorsmentioning

confidence: 99%

Update of Sepsis in the Intensive Care Unit

Genga¹,

Russell²

2017

J Innate Immun

116

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“…Multiple pharmacological agents are available to treat intraoperative hypotension that target the sympathetic system (Gamper et al, 2016). …”

Section: Introductionmentioning

confidence: 99%

AkrinorTM, a Cafedrine/ Theodrenaline Mixture (20:1), Increases Force of Contraction of Human Atrial Myocardium But Does Not Constrict Internal Mammary Artery In Vitro

et al. 2017

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Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. AkrinorTM consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of AkrinorTM and its constituents on contractile force and tension in human atrial trabeculae and internal A. mammaria rings.Methods: Isometric contractions were measured in human atrial trabeculae at 1 Hz and 37°C. CGP 20712A and ICI 118,551 were used to elaborate β1- and β2-adrenoceptor (AR) subtypes involved and phenoxybenzamine to estimate indirect sympathomimetic action. PDE-inhibition was measured as a potentiation of force increase upon direct activation of adenylyl cyclase by forskolin. Human A. mammaria preparations were used to estimate intrinsic vasoconstriction and impact on the noradrenaline-induced vasoconstriction.Results: Clinically relevant concentrations of AkrinorTM (4.2–420 mg/l) robustly increased force in human atrial trabeculae (EC50 41 ± 3 mg/l). This direct sympathomimetic action was mediated via β1-AR and the effect size was as large as with high concentrations of calcium. Only the highest and clinically irrelevant concentration of AkrinorTM increased the potency of forskolin to a minor extent. Norephedrine has lost its indirect sympathomimetic effect when bound to theophylline. Increasing concentrations of AkrinorTM (4.2–168 mg/l) alone did not affect the tension of human A. mammaria interna rings, but shifted the noradrenaline curve rightward from -logEC50 6.18 ± 0.08 to 5.23 ± 0.05 M.Conclusion: AkrinorTM increased cardiac contractile force by direct sympathomimetic actions and PDE inhibition, did not constrict A. mammaria preparations, but shifted the concentration-response curve to the right, compatible with an α-AR antagonistic effect or PDE inhibition. The pharmacodynamic profile and potency of AkrinorTM differs from noradrenaline and norephedrine in vitro. We anticipate metabolism of theodrenaline and cafedrine resulting in a different pharmacodynamic profile of AkrinorTM in vivo.

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“…We refrain from giving any recommendations or suggestions on using dobutamine or dopamine for patients with shock after cardiac surgery, due to the lack of data and no relevant populations to extrapolate from. Importantly, we recommend that if clinicians prefer to use dopamine rather than dobutamine in this population, they do so in the context of high‐quality RCTs, given the harm associated with use of dopamine in patients with septic shock17, 18 and in a subgroup analysis of patients with cardiogenic shock in the SOAP 2 trial 39

We suggest against routine use of dobutamine as inotropic agent for patients with shock after cardiac surgery, as compared to placebo/no treatment (weak recommendation, very low quality of evidence).

…”

Section: Resultsmentioning

confidence: 99%

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure

Møller

Granholm

Junttila

et al. 2018

Acta Anaesthesiol Scand

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BackgroundAdult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient‐important treatment recommendations on this topic.MethodsThis guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient‐important outcome measures, including mortality and serious adverse reactions.ResultsFor all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions.ConclusionsWe suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.

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Vasopressors for hypotensive shock

Cited by 138 publications

References 93 publications

Update of Sepsis in the Intensive Care Unit

Update of Sepsis in the Intensive Care Unit

AkrinorTM, a Cafedrine/ Theodrenaline Mixture (20:1), Increases Force of Contraction of Human Atrial Myocardium But Does Not Constrict Internal Mammary Artery In Vitro

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure

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