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

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).

Feasibility, Utility, and Safety of Midodrine During Recovery Phase From Septic Shock.

BACKGROUND: We describe the feasibility, utility, and safety of oral midodrine to replace IV vasopressors during recovery from septic shock. METHODS: This was a retrospective study performed in a medical ICU. All study subjects had a diagnosis of septic shock requiring at least 24 hours of IV vasopressors and demonstrated clinical stability with stable or decreasing doses of IV vasopressors. The two groups compared were those who received IV vasopressors only and those who received IV vasopressors with adjunctive midodrine. RESULTS: Of the 275 study patients, 140 received an IV vasopressor only and 135 received midodrine in addition to an IV vasopressor. There was no difference between the groups' demographics (age, sex, Acute Physiology and Chronic Health Evaluation 4 score). Mean IV vasopressor duration was 3.8 days in the IV vasopressor only group and 2.9 days in the IV vasopressor with midodrine group (P < .001). An IV vasopressor was reinstituted after discontinuation in 21 of 140 (15%) patients in the IV vasopressor only group and in 7 of 135 (5.2%) patients in the IV vasopressor with midodrine group (P = .007). ICU length of stay was 9.4 days in the IV vasopressor only group and 7.5 days in the IV vasopressor with midodrine group (P = .017). There were no complications associated with midodrine use except transient bradycardia in one patient, which resolved upon discontinuation of midodrine. CONCLUSIONS: Midodrine may reduce the duration of IV vasopressors during recovery phase from septic shock and may be associated with a reduction in length of stay in the ICU.

Selection factors for local anesthetic agents.

The decision to inject local anesthetic agents to achieve profound anesthesia is dependent upon many factors, particularly the depth and duration of anesthesia required, and the possible need for hemostasis. To maximize the safety of local anesthetic injections, it is necessary to weigh the risks against the benefits for each patient, for each anesthetic agent, for use of a vasoconstrictor, and for the delivery technique for the selected agent.

Veno-active drugs in the management of chronic venous disease. An international consensus statement: current medical position, prospective views and final resolution.

BACKGROUND: Veno-active drugs (VAD) have effects on edema and symptoms related to chronic venous disease (CVD), especially so-called venous pain. VAD's effectiveness, although well established, is regularly debated. OBJECTIVE: Our purpose was to select all randomized controlled trials (RCTs) and meta-analyses devoted to VAD and symptoms in CVD, to submit them to a group of international experts in CVD and to vote with secrete ballot to determine the level of efficacy of each drug, according to EBM (Evidence-Based Medicine) rules and critical analysis. METHODS: Publications in any language devoted to VAD and venous symptoms were searched for in different databanks and submitted to the experts prior to the meeting. RESULTS: 83 papers were analyzed, including 72 RCTs or meta-analyses. Experts determined the level of EBM of each drug, according to the literature and personal experience, using 3 levels of recommendation, A, B and C (from large RCTs to non-randomized trials). CONCLUSIONS: VAD are effective and may be applied in CVD when symptomatic, from C0s to C6s. However, etiological treatment of venous reflux and venous hypertension has always priority. In some cases VAD may replace compression and/or complement its effects. If respecting these prerequisites, VAD are safe and effective.

Vasopressor agents: old and new components.

PURPOSE OF REVIEW: In settings of cardiac arrest, reestablishing vital organ perfusion plays an important role in initial CPR. As a pharmacologic intervention, vasopressor agents aim to improve aortic diastolic pressure and, consequently, coronary and cerebral perfusion pressures. RECENT FINDINGS: Historically, adrenergic agonists such as epinephrine have been suggested for routine use in CPR. However, epinephrine's efficacy is controversial because of its unfavorable inotropic and chronotropic action. This has prompted research into the use of alternative pressor agents with more promising hemodynamic features; these include selective alpha 2-adrenergic agonists and other nonadrenergic vasoconstrictors such as vasopressin. SUMMARY: In this article, the main traditional and novel adrenergic and nonadrenergic vasopressor drugs are reviewed.

Papel de la agiotensina II en el desarrollo aterosclerótico: efecto de su bloqueo / Role of angiotensin II in the development of atherosclerosis: effect of blockade

La angiotensina II, el principal efector del sistema renina-angiotensina, ejerce un papel importante en la génesis y en las complicaciones de la aterosclerosis. La angiotensina II estimula la producción de especies reactivas de oxígeno en el vaso que desempeñan un papel clave en la disfunción endotelial y en la oxidación de las lipoproteínas de baja densidad (LDL). Asimismo, este péptido participa en la inducción de la respuesta inflamatoria en la pared vascular mediante la producción de moléculas de adhesión y citoquinas quimiotácticas y proinflamatorias. La angiotensina II, además, estimula la proliferación y migración de células de músculo liso y modula el cambio fenotípico de las mismas dando lugar a un aumento de la síntesis de la matriz extracelular. Finalmente, la angiotensina II también participa en las complicaciones de la aterosclerosis al favorecer la ruptura de la placa y trombogenicidad de la misma. En consecuencia, el sistema renina-angiotensina desempeña un papel clave en la patofisiología de la aterosclerosis, por lo que su bloqueo ejercerá un efecto beneficioso sobre el desarrollo aterosclerótico previniendo las alteraciones trombóticas asociadas a él (AU)

TIPS or vasoconstrictors for the treatment of hepatorenal syndrome type 1--effect on survival?

HRS is a serious complication in patients with cirrhosis and ascites and associated with a poor prognosis unless liver transplantation can be performed. Two different types of HES are being differentiated according to the clinical presentation: while HRS type I is characterised by rapid deterioration of renal function indicated by a two-fold increase of serum creatinine to values above 2.5 mg/dl or a decrease of creatinine clearance to values below 20 ml/min, HRS type II shows moderately increased serum creatinine above 1.5 mg/dl remaining stable over a longer period. The most prominent circulatory alterations in patients with chronic liver disease comprise portal hypertension and peripheral (mainly splanchnic) arterial vasodilation. This leads to a decreased centrally effective blood volume in cirrhotic patients. As a consequence, activation of sodium- and volume-retaining neurohumoral systems such as the renin-angiotensin-aldosterone system and the sympathetic nervous system and a non-osmotic release of arginine-vasopressin can be observed. These neurohumoral alterations induce renal sodium and water retention which are responsible for accumulation of ascites and deterioration of renal function. Recent therapeutic strategies of the hepatorenal syndrome take into account these pathophysiologic considerations: whereas the transjugular intrahepatic portosystemic shunt lowers portal hypertension, infusion of vasoactive drugs increases systemic vascular resistance in cirrhotic patients. Several uncontrolled trials have reported a positive effect of these strategies on renal function. The present analysis of combined data from these reports shows that this positive effect on renal function also may improve survival of patients with HRS type I.

Non-conventional vasopressors in septic shock: effects on hepatosplanchnic blood flow.

Vasopressors are necessary to treat the vasodilation characteristic of hypotension in septic shock. In addition to noradrenaline, the reference vasopressor, various drugs, including dopamine, adrenalin, phenylephrine, L-NMMA (a nitric oxide synthase inhibitor), and vasopressin have been used in clinical septic shock. The available clinically relevant data on the effects of "non-conventional" vasopressors on splanchnic circulation is very limited or nonexistent, and their safety has not been demonstrated. All these drugs can modify the perfusion and metabolism of splanchnic organs, changes which cannot be predicted from changes in systemic circulation or metabolism. Due to the complexity of actions and the high potential for severe adverse effects, "compassionate" use of unconventional vasopressors to treat hypotension in septic shock should be abandoned outside the scope of controlled clinical trials.