Systolic-dicrotic notch pressure difference can identify tachycardic patients with septic shock at risk of cardiovascular decompensation following pharmacological heart rate reduction

Morelli, Andrea; Romano, Salvatore Mario; Sanfilippo, Filippo; Santonocito, Cristina; Frati, Giacomo; Chiostri, Marco; Ertmer, Christian; Rehberg, Sebastian; Vieillard‐Baron, Antoine

doi:10.1016/j.bja.2020.05.058

Cited by 30 publications

(27 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, the very short half-life of esmolol in this indication allows a rapid reversibility of potential deleterious hemodynamics effects. Therefore, in a number of patients, elevated heart rate may be compensatory for decreased contractility rather than noncompensatory (sympathetic overstimulation), even in the later phases of septic shock (8). The present study has several limitations.…”

Section: Discussionmentioning

confidence: 85%

“…(7). On the other hand, an early use of beta-blockers might be difficult due to the challenge in distinguishing between the compensatory or non-compensatory origin of tachycardia (8). Indeed, in the very early phase of septic shock, the combinational effects of inflammatory mediators, fluid loading and increasing afterload with NE may worsen myocardial contractility.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study

et al. 2021

Self Cite

View full text Add to dashboard Cite

Background Several studies have shown that heart rate control with selective beta-1 blockers in septic shock is safe. In these trials, esmolol was administered 24 h after onset of septic shock in patients who remained tachycardic. While an earlier use of beta-blockers might be beneficial, such use remains challenging due to the difficulty in distinguishing between compensatory and non-compensatory tachycardia. Therefore, the Esmosepsis study was designed to study the effects of esmolol aimed at reducing the heart rate by 20% after the initial resuscitation process in hyperkinetic septic shock patients on (1) cardiac index and (2) systemic and regional hemodynamics as well as inflammatory patterns. Methods Nine consecutive stabilized tachycardic hyperkinetic septic shock patients treated with norepinephrine for a minimum of 6 h were included. Esmolol was infused during 6 h in order to decrease the heart rate by 20%. The following data were recorded at hours H0 (before esmolol administration), H1–H6 (esmolol administration) and 1 h after esmolol cessation (H7): systolic arterial pressure, diastolic arterial pressure, mean arterial pressure, central venous pressure, heart rate, PICCO transpulmonary thermodilution, sublingual and musculo-cutaneous microcirculation, indocyanine green clearance and echocardiographic parameters, diuresis, lactate, and arterial and venous blood gases. Results Esmolol was infused 9 (6.4–11.6) hours after norepinephrine introduction. Esmolol was ceased early in 3 out of 9 patients due to a marked increase in norepinephrine requirement associated with a picture of persistent cardiac failure at the lowest esmolol dose. For the global group, during esmolol infusion, norepinephrine infusion increased from 0.49 (0.34–0.83) to 0.78 (0.3–1.11) µg/min/kg. The use of esmolol was associated with a significant decrease in heart rate from 115 (110–125) to 100 (92–103) beats/min and a decrease in cardiac index from 4.2 (3.1–4.4) to 2.9 (2.5–3.7) l/min/m−2. Indexed stroke volume remained unchanged. Cardiac function index and global ejection fraction also markedly decreased. Using echocardiography, systolic, diastolic as well as left and right ventricular function parameters worsened. After esmolol cessation, all parameters returned to baseline values. Lactate and microcirculatory parameters did not change while the majority of pro-inflammatory proteins decreased in all patients. Conclusion In the very early phase of septic shock, heart rate reduction using fast esmolol titration is associated with an increased risk of hypotension and decreased cardiac index despite maintained adequate tissue perfusion (NCT02068287).

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Moreover, formulations contain compound 1 or 5 resulted in a significant reduction in the difference between systolic and dicrotic pressure (SDP difference) compared to plain IV formulation at doses 12, 24, and 36 μg/kg ( p < 0.05, Figure 4C ). The SDP difference is important in reflecting the coupling between myocardial contractility and a given afterload ( Morelli et al, 2020 ). Previously Senzaki et al suggested that increased afterload rather than reduced contractility impairs ventricular-arterial coupling ( Senzaki et al, 2006 ).…”

Section: Resultsmentioning

confidence: 99%

Self-Nanoemulsifying Drug Delivery System Loaded with Psiadia punctulata Major Metabolites for Hypertensive Emergencies: Effect on Hemodynamics and Cardiac Conductance

et al. 2021

View full text Add to dashboard Cite

Vasodilators are an important class of antihypertensive agents. However, they have limited clinical use due to the reflex tachycardia associated with their use which masks most of its antihypertensive effect and raises cardiac risk. Chemical investigation of Psiadia punctulata afforded five major methoxylated flavonoids (1–5) three of which (1, 4, and 5) showed vasodilator activity. Linoleic acid-based self-nanoemulsifying drug delivery system (SNEDDS) was utilized to develop intravenous (IV) formulations that contain compounds 1, 4, or 5. The antihypertensive effect of the prepared SNEDDS formulations, loaded with each of the vasodilator compounds, was tested in the angiotensin-induced rat model of hypertension. Rats were subjected to real-time recording of blood hemodynamics and surface Electrocardiogram (ECG) while the pharmaceutical formulations were individually slowly injected in cumulative doses. Among the tested formulations, only that contains umuhengerin (1) and 5,3′-dihydroxy-6,7,4′,5′-tetramethoxyflavone (5) showed potent antihypertensive effects. Low IV doses, from the prepared SNEDDS, containing either compound 1 or 5 showed a marked reduction in the elevated systolic blood pressure by 10 mmHg at 12 μg/kg and by more than 20 mmHg at 36 μg/kg. The developed SNEDDS formulation containing either compound 1 or 5 significantly reduced the elevated diastolic, pulse pressure, dicrotic notch pressure, and the systolic–dicrotic notch pressure difference. Moreover, both formulations decreased the ejection duration and increased the non-ejection duration while they did not affect the time to peak. Both formulations did not affect the AV conduction as appear from the lack of effect on p duration and PR intervals. Similarly, they did not affect the ventricular repolarization as no effect on QTc or JT interval. Both formulations decreased the R wave amplitude but increased the T wave amplitude. In conclusion, the careful selection of linoleic acid for the development of SNEDDS formulation rescues the vasodilating effect of P. punctulata compounds from being masked by the reflex tachycardia that is commonly associated with the decrease in peripheral resistance by most vasodilators. The prepared SNEDDS formulation could be suggested as an effective medication in the treatment of hypertensive emergencies, after clinical evaluation.

show abstract

“…As a consequence, the cardiac index remained unchanged, and mean arterial pressure and dose of norepinephrine were also similar between groups. 10 Several aspects behind these results need to be discussed.…”

mentioning

confidence: 99%

“…Such a distinction is crucial to establish which patient will benefit or eventually be harmed from controlling tachycardia. 10 Although conventional hemodynamic parameters and echocardiography may suggest conditions in which tachycardia should not be treated, they also may fail in detecting a covert loss of myocardial contractility (which often occurs in septic shock) compensated by tachycardia. Such "hidden" myocardial dysfunction may become evident only after HR reduction.…”

mentioning

confidence: 99%

Ultrashort-Acting β-Blockers

Morelli¹,

Sanfilippo

2021

Chest

Self Cite

View full text Add to dashboard Cite

Systolic-dicrotic notch pressure difference can identify tachycardic patients with septic shock at risk of cardiovascular decompensation following pharmacological heart rate reduction

Cited by 30 publications

References 31 publications

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study

Hemodynamic and anti-inflammatory effects of early esmolol use in hyperkinetic septic shock: a pilot study

Self-Nanoemulsifying Drug Delivery System Loaded with Psiadia punctulata Major Metabolites for Hypertensive Emergencies: Effect on Hemodynamics and Cardiac Conductance

Ultrashort-Acting β-Blockers

Contact Info

Product

Resources

About