Vasopressors During Sepsis

Gelinas, Jean Pierre; Russell, James A.

doi:10.1016/j.ccm.2016.01.008

Cited by 14 publications

(3 citation statements)

References 84 publications

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“…In septic shock, dobutamine is recommended to increase cardiac output (CO) when hypoperfusion causes an impairment of end-organ function despite achieving adequate intravascular volume and mean arterial pressure (12). However, limited clinical outcome measures have been provided as to advisability of the usefulness of dobutamine in septic shock management (21). In clinical practice, patients with septic shock may suffer from hypotension and cardiac dysfunction refractory to dobutamine.…”

mentioning

confidence: 99%

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation

Sakai

Suzuki

Tomita

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

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Dobutamine has been used in septic shock for many years as an only inotrope, but its benefit has been questioned. We weighed the effects of dobutamine and milrinone as inotropes in mice with cecal ligation and puncture (CLP)-induced polymicrobial sepsis. CLP-induced septic mice exhibited significant cardiac inflammation, as indicated by greatly increased mRNAs of proinflammatory cytokines and robust infiltration of inflammatory cells in the ventricular myocardium. Elevations of plasma cardiac troponin-I showed cardiac injury in CLP mice. Noninvasive echocardiographic assessment of cardiac function revealed that despite preserved left ventricular function in the presence of fluid replacement, the dobutamine inotropic response was significantly impaired in CLP mice compared with sham-operated controls. By contrast, milrinone exerted inotropic effects in sham-operated and CLP mice in an equally effective manner. Surface expression levels of β-adrenoceptors and α-subunits of three main G protein families in the myocardium were unaffected by CLP-induced sepsis. Plasma cAMP levels were significantly elevated in both sham-operated and CLP mice in response to milrinone but only in sham-operated controls in response to dobutamine. Of phosphodiesterase (PDE) isoforms, PDE4D, but not PDE3A, both of which are responsible for cardiac cAMP hydrolysis, was significantly upregulated in CLP mouse myocardium. We define a novel mechanism for the impaired responsiveness to dobutamine as an inotrope in sepsis, and understanding the role of PDE4D in modulating cardiac functional responsiveness in sepsis may open the potential of a PDE4D-targeted therapeutic option in septic patients with low cardiac output who have a need for inotropic support. Advisability of the usefulness of dobutamine in septic shock management is limited. Here, we reveal that the effect of dobutamine as a positive inotrope is impaired in mice with cecal ligation and puncture-induced sepsis without changes in cardiac β-adrenoceptor signaling as a result of cAMP breakdown achieved by upregulated phosphodiesterase 4D.

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mentioning

confidence: 99%

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation

Sakai

Suzuki

Tomita

et al. 2017

American Journal of Physiology-Heart and Circulatory Physiology

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“…Hypotension occurs in sepsis as a result of venous and arterial vasoplegia, hypovolemia and myocardial depression. In studies, vasopressor agents such as norepinephrine, epinephrine, vasopressin, dopamine, terlipressin, phenylephrine and inotropic agents such as dobutamine, dopexamine, milrinone and levosimendan were used (11). According to the Surviving Sepsis Campaign guideline, norepinephrine is the first choice for vasopressor support when there is no response to fluid therapy in septic shock (1).…”

Section: Discussionmentioning

confidence: 99%

“…The median ages of the patients were 68 (54.2-79) years, and 239 (61%) were male. Median Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA) values were 24.5 (18)(19)(20)(21)(22)(23)(24)(25)(26)(27) and 11 (9)(10)(11)(12), respectively. While the duration of ICU stay was 10(4-22) days, the rates of patients with invasive mechanical ventilation, blood and blood products transfusion and acute kidney injury were 96.9% (380 patients), 58.9% (231 patients) and 26.3% (103 patients), respectively.…”

Section: General Characteristics Of Patients With Sepsis / Septic Shockmentioning

confidence: 99%

The use of Vasoactive-Inotropic Score in Adult Patients with Septic Shock in Intensive Care

Kara¹,

Sargın²,

Bayraktar³

et al. 2019

Yoğun Bakım Derg

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Objective: Sepsis and septic shock are significant causes of mortality and morbidity. In septic shock, vasopressors and inotropic support are given for the treatment of hypotension. This study was designed to investigate the relationship between the vasoactive-inotropic score (VIS) and the results of sepsis patients in ICU. Methods: The data of 392 patients who were followed up with the diagnosis of septic shock in adult ICU were recorded retrospectively. Vasopressors and inotropic support of the patients during the first 48 hours after the diagnosis of septic shock were recorded. Mean and peak VIS values were calculated according to these values. The patients were divided into groups according to the mean VIS≥10, peak VIS≥10 and intensive care results and statistical analysis was performed. Results: The median ages of the patients were 68 (54.25-79) years and 239 (61%) were male. Dopamine 188 (47.9%), noradrenaline 365 (93.1%), adrenaline 53 (13.5%) and dobutamine 15 (3.8%) were used in the patients. The mean VIS was 9 (4-15), while the number of mean VIS≥10 patients were 192 (49%). Peak VIS values were 11 (5-20), and the number of peak VIS ≥10 patients were 220 (56.1%). The mortality rate of the patients included in the study was 42.1%. The mean VIS score(13 vs 6, p=0.000), mean VIS≥10 patient ratio (71.5% vs 32.6%, p=0.000), peak VIS score (16 vs 8, p=0.000), and peak VIS ≥10 patient ratio (73.3% vs 43.6%, p=0.000) were higher in non-survivors. The parameters such as mean VIS [OR 1.123, 95% CI 1.027-1.229, p=0.011], mean VIS≥10 [OR 3.455, 95% CI 1.625-7.345, p=0.001] and peak VIS score [OR 0.917, 95% CI 0.851-0.989, p=0.024] were determined as independent risk factors for mortality. Conclusion: We conclude that vasoactive-inotropic score may be useful in predicting the outcome of septic shock patients in intensive care units.

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Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis

Yamashita

Suzuki

Iguchi

et al. 2018

Naunyn-Schmiedeberg's Arch Pharmacol

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Levosimendan and milrinone may be used in place of dobutamine to increase cardiac output in septic patients with a low cardiac output due to impaired cardiac function. The effects of the two inotropic agents on cardiac inflammation and left ventricular (LV) performance were examined in mice with cecal ligation and puncture (CLP)-induced sepsis. CLP mice displayed significant cardiac inflammation, as indicated by highly increased pro-inflammatory cytokines and neutrophil infiltration in myocardial tissues. When continuously given, levosimendan prevented but milrinone exaggerated cardiac inflammation, but they significantly reduced the elevations in plasma cardiac troponin-I and heart-type fatty acid-binding protein, clinical markers of cardiac injury. Echocardiographic assessment of cardiac function showed that the effect of levosimendan, given by an intravenous bolus injection, on LV performance was impaired in CLP mice, whereas milrinone produced inotropic responses equally in sham-operated and CLP mice. A lesser effect of levosimendan on LV performance after CLP was also found in spontaneously beating Langendorff-perfused hearts. In ventricular myocytes isolated from control and CLP mice, levosimendan, but not milrinone, caused a large increase in the L-type calcium current. This study represents that levosimendan and milrinone have cardioprotective properties but provide different advantages and drawbacks to cardiac inflammation/dysfunction in sepsis.

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Vasopressors During Sepsis

Cited by 14 publications

References 84 publications

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation

Diminished responsiveness to dobutamine as an inotrope in mice with cecal ligation and puncture-induced sepsis: attribution to phosphodiesterase 4 upregulation

The use of Vasoactive-Inotropic Score in Adult Patients with Septic Shock in Intensive Care

Cardioprotective and functional effects of levosimendan and milrinone in mice with cecal ligation and puncture-induced sepsis

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