Dobutamine for sepsis why

From this perspective, we will soon have to rethink regarding dobutamine use in patients with sepsis. Abstract Dobutamine is commonly used worldwide and included in the protocol for early goal-directed therapy EGDT. Adverse event of acute coronary syndrome should be suspected in patients with chest pain and elevated cardiac enzymes during treatment with vasopressin In conclusion, vasopressin can be an alternative medication but is not recommended as a first line treatment of septic shock.

Terlipressin is an analogue of vasopressin and can be used as a vasoactive drug in the management of low blood pressure induced by septic shock. Similar to vasopressin, it can be used as a rescue therapy for septic shock when shock is refractory to conventional treatment Terlipressin was found to have equivalent effect on raising MAP, but it was associated with decreased cardiac index and oxygen consumption In another study using terlipressin as the first line therapy, it reduced norepinephrine requirement and the rate of rebound hypotension was lower than the control group Phenylephrine is a potent vasoconstrictor without significant effect on cardiac function.

The highly selective action site of phenylephrine makes it unique in all vasopressors. From hemodynamic perspective, it increases mean arterial pressure, but lowers cardiac output. There is no effect on heart rate. As compared with norepinephrine, phenylephrine has no additional beneficial effect on cardiopulmonary performance, global oxygen transport, and regional hemodynamics in the initial resuscitation of septic shock In a small RCT, phenylephrine is superior to norepinephrine in reducing heart rate and increasing systemic vascular resistance As compared to other vasopressors, phenylephrine receives fewer attentions in medical literature.

Before new evidence emerges, we suggest use of phenylephrine in patients with prominent tachycardia and low systemic vascular resistance. Sepsis or its severe form septic shock is always associated with tachycardia, and tachycardia per se is an item in the list of sepsis diagnostic criteria. Pathophysiologically, tachycardia is associated with more oxygen consumption, making oxygen debt more prominent in patients with severe sepsis and septic shock.

Therefore, it is reasonable to rest heart by reducing its beating rate. This theoretical hypothesis has been verified in burn children While it is theoretically plausible, experimental and clinical studies yielded conflicting results 5 - 7 , 48 , Observational studies showed that esmolol, the most commonly used beta-blocker in septic shock, was associated with economization of cardiac work and oxygen consumption.

Also there are some evidence that esmolol administration was associated with reduced norepinephrine requirement The most important clinical trial that has been published is probably the one performed by Morelli and colleagues. This was a large effect size and if verified in large multi-center trials it can be a milestone in the history of the treatment of septic shock.

Two main concerns have compromised the generalizability of the study. Although the authors explained the high mortality by the presence of multidrug-resistant Gram-negative organisms, this is not convincing. Concerns regarding the negative inotropic action of beta-blocks have been raised in septic shock. Therefore, some studies have investigated the combined use of beta-blockers and inotropes milrinone 51 , What does all this mean? Well what this means is that the intern may have, in fact, been correct to suggest that we use dobutamine for our now hypotensive patient.

It all depends on the suspected cause IE: cardiogenic vs septic vs other causes of hypotension. It is important to keep in mind, though, that unless this patient has a purely cardiogenic cause such as severe heart failure , they may also require a second pressure support in order to maintain a healthy blood pressure. Phillip, Mitchell M. Levy, Jean M. Carlet, Julian Bion, Margaret M. Parker, Roman Jaeschke, Konrad Reinhart, et al. B 14, no.

A Prospective, Randomized Pilot Study. Wells Askew, and Nandan S. Urbanek, C. Inotropic agents are important therapeutic options for SICM, which are used to increase the force of cardiac contractions and improve hemodynamics. Levosimendan, another attractive inotrope for cardiogenic shock in SICM, which optimizes hemodynamics with both left ventricle LV and right ventricle RV function in a catecholamine-independent pattern to minimize oxygen demand, arrhythmia, and catecholamines resistance for sepsis via calcium sensitization 7 , 8 , 9.

Whether levosimendan is superior to dobutamine remains a highly contentious issue, previous studies were characterized by a wide variety of opinions on this topic 7 , 10 , While few of these studies have focused on prognosis of cardiac function and outcome in patients with sepsis-induced cardiac dysfunction.

More importantly, these studies did not take changes in quantitative parameters such as ejection fraction into account with baseline level. In this meta-analysis, we aimed to determine the effects of levosimendan, comparing to dobutamine on prognosis of cardiac function, mortality and clearance of serum lactic acid in SICM patients and provide recommendations for clinical practice.

We searched Google Scholar, PubMed, Cochrane Library, Embase for potentially eligible trials by screening titles and reviewing abstracts, with no filters or publication status or language restrictions. Two independent investigators W. Inclusion criteria were prespecified according to the PICOS population, intervention, comparison, outcomes, and study design approach Table 1.

Randomized trials and observational studies on the use of levosimendan in adult patients with severe sepsis and septic shock will be included if reporting our primary outcomes cardiac function parameters at the time point of baseline and h, including CI, LVEF and LVSWI and our secondary outcomes all-cause mortality in ICU and blood lactate at the time point of baseline and h.

References of the previously published meta-analyses were also examined for eligible articles. Two reviewers Y. One study did not report CI; however, we decided to include this article to calculate other new functional indexes. Data extraction was performed to capture information on study-related, participant-related, and treatment-related characteristics.

Authors of studies eligible for inclusion in our review were contacted if original data were missing. Two authors Y. We extracted data on one primary outcome and two secondary outcomes.

Modified Jadad scale Table 2 was used to assess the quality of evidence from the included studies 1—3 for low quality and 4—7 for high quality : random sequence production adequate, unclear, inadequate , allocation concealment adequate, unclear, inadequate , blinding method adequate, unclear, inadequate , withdrawal described, undescribed.

Differences in judgment were resolved by group discussion. If data was presented as median [25th;75thpercentile], the mean and standard deviation SD were estimated by median and quartile spacing by the corresponding formula, and the change of mean and SD from baseline after h treatment is also calculated, according to the formula provided by Cochrane Handbook for Systematic Reviews of Interventions Version 6.

The data was analyzed as recommended in the Cochrane Handbook for Systematic Reviews of Interventions To assess the between-trial heterogeneity, the I 2 was applied 19 , The importance of this measure depends on the magnitude and direction of effects as well as the precision of the estimate often judged by the corresponding P value from the chi-squared test The presence of publication bias was assessed by funnel plot Fig.

All analyses were performed with R version 4. This article does not contain any studies with human participants or animals performed by any of the authors. We screened article titles and abstracts from the electronic databases and removed duplicates Fig. Due to a lack of relevant information about our predefined outcome parameters, only 13 articles were retrieved for full-text assessment. Finally, the remaining 6 studies 7 , 14 , 15 , 16 , 17 , 18 were included in our quantitative analysis.

We included 6 studies involving patients, including 97 patients in the experimental group and 95 patients in the control group. The minimum sample size was 10, and the maximum sample size was Table 3 showed the detailed characteristics and main conclusions of all studies.

The RCTs were published between and Change before-after comparison to the baseline of cardiac function at the time point of h. All the included studies reported serum lactic acid at the time point of baseline and h. Clearance of serum lactic acid.

All the included studies reported survival status in ICU. The heterogeneity mainly existed in the result of the changes of cardiac function parameters; therefore, the sensitivity analysis was only conducted for this part Fig.

After removing the studies from the corresponding groups, the fixed-effect model was used to pool the effect sizes Fig.

The results showed that levosimendan could improve cardiac function to a certain extent. Sensitivity analysis of the changes of cardiac function parameters.

Change of cardiac function at the time point of h after removing the studies from the corresponding groups. To our knowledge, this is the first meta-analysis to summarize the current evidence of changes in cardiac function of SICM patients at the time point of h after the administration of levosimendan before-after comparison to the baseline.

The meta-analysis results of the available data showed that levosimendan might have a significant improvement of CI and decrease of blood lactate in septic patients with myocardial dysfunction in ICU after h administration of levosimendan than dobutamine. International guidelines recommend a trial of dobutamine in the case of tissue hypoperfusion or myocardial dysfunction Dobutamine can improve myocardial contractility in patients with septic shock by exciting the myocardial beta-receptor 27 , Although it has also been found that dobutamine can improve the microcirculation and peripheral tissue 29 , while some clinical trials suggested that dobutamine cannot improve the outcome of septic shock patients, and even increase the mortality of 90 days 30 , Levosimendan, as a calcium sensitizer, is another attractive inotrope for cardiogenic shock in SICM.

Unlike other inotropic agents, the positive inotropic effect of levosimendan is independent of the production of cyclic adenosine monophosphate cAMP 32 , 33 , so it could minimize oxygen demand, arrhythmia, and catecholamines resistance 7 , 8 , 9. This property is of great significance for myocardial inhibition in septic patients under the hyperdynamic metabolic state.

This characteristic is of great significance for myocardial depression in septic shock with high dynamic metabolism. Decreased peripheral vascular resistance is one of the hemodynamic characteristics in septic shock and reduces left ventricular afterload In animal experiments and clinical studies, levosimendan can lead to low blood pressure secondary to decreased peripheral vascular resistance, which correlates with its loading doses Instead of using a loading dose, a continuous intravenous infusion dose of 0.

At the same time, patients in levosimendan group received more fluid and had more urinary output than patients in dobutamine group Table 4 and there was no significant difference of the use of norepinephrine at baseline and after 24 h between the experimental and the control group.

Even though fluid input was different between two groups, septic shock patients were randomized to receive either levosimendan 0. Therefore, the improvement of left ventricular systolic dysfunction induced by levosimendan may be attributed to the fact that levosimendan could improve LV ejection capacity At the same time, patients were given an adequate fluid input and thus not presented with a fall in blood pressure. Although patients in levosimendan group received more fluid than patients in dobutamine group, there was no significant difference in both urine volume and EVLWI measured via PiCCO device, which may be explained by the fact that levosimendan could improve LV ejection capacity and reduce venous pressure.

Previous studies have suggested that dobutamine improves cardiac contractility in patients with septic shock and that its use combined with other vasoactive agents has the potential to improve MAP Nevertheless, the present study did not show that dobutamine was superior to levosimendan in improving the CI index, probably due to beta-receptor down regulation in septic shock Moreover, there is also an increased risk of arrhythmias if high doses of dobutamine are used.

Although the clearance of serum lactic acid in the levosimendan group increased significantly at h after administration than in the dobutamine group, it could not be suggested that levosimendan could improve tissue perfusion due to more fluid input in levosimendan group at h after administration. The effect of fluid resuscitation for tissue perfusion and organ protection in patients with septic shock is definite, and decreased lactate concentrations can not yet be deduced by the direct effect of levosimendan.

Although lactate clearance could reflect microcirculation to a certain extent, it is far less intuitive than Sidestream Dark Field SDF imaging, a new way for clinical observation of microcirculation. In this modality, a light guide imaging the microcirculation is surrounded by light-emitting diodes of a wavelength nm absorbed by erythrocyte hemoglobin to be clearly observed as flowing cells. This method of observing microcirculation provides a clear image of capillary without blurring The development of new imaging methods, such as SDF, is more helpful to determine the critical role of treatments in improving microcirculation in sepsis.

Both levosimendan and dobutamine could improve LVEF. But according to the results of this study, there was no significant difference in the improvement of LVEF in the levosimendan group compared with the dobutamine group. The evaluation of left ventricular LV systolic function is of great significance for the evaluation and treatment of patients with heart disease.

LVEF measured by echocardiography is one of the most commonly used indications Previous studies had suggested that poor agreement were revealed among different methods measuring LVEF and the Simpson method had a more predictivity than the Teichholz method in evaluating LV function However, only three of the included studies clearly stated that LVEF was measured by the Simpson method see Fang 15 , Meng 16 , and Xu 18 and other included literature did not.

Ejection fraction calculated by Teichholz method with M-mode echocardiography from the parasternal long axis or short axis 44 , which are more susceptible to limited patient mobility and possibly mechanical ventilation It is difficult for even skilled echocardiographers to image in ICU settings.

If the Teichholz method was used to measure EF in the other studies, it might increase the heterogeneity resulting in false negative result.