Hemodynamic effects of a continuous infusion of levosimendan in critically ill patients with cardiogenic shock requiring catecholamines

BACKGROUND: Levosimendan, a novel inodilator, has been shown to improve hemodynamic function in patients with decompensated heart failure with preserved arterial blood pressure. Data on its use in patients with cardiogenic shock are rare. The present series describes the 24-h hemodynamic effects of levosimendan as add-on therapy in desperately ill patients with cardiogenic shock requiring catecholamines. METHODS: Ten patients with cardiogenic shock received levosimendan as continuous infusion of 0.1 microg kg(-1) min(-1) for 24 h. The patients were otherwise unselected. Hemodynamic measurements were routinely performed at baseline (time 0) and at 1, 8, 16 and 24 h after start of levosimendan (LS) using a Swan-Ganz thermodilution catheter. RESULTS: During the levosimendan infusion there was a significant increase in cardiac index from 1.8 +/- 0.4 to 2.4 +/- 0.6 L*min-1*m-2 (P = 0.023) and a significant decrease in systemic vascular resistance from 1559 +/- 430 to 1109 +/- 202 dyn*s*cm-5 (P = 0.001), respectively. Changes in catecholamine dose, and in systolic and diastolic blood pressure were not significant. Given the individual response to LS, 8/10 patients showed an increase in left ventricular stroke work index under reduced or roughly unchanged preload conditions after 8 h. CONCLUSION: This series shows that a LS infusion is feasible and able to improve hemodynamics in severely compromized, critically ill patients with cardiogenic shock requiring catecholamine therapy. Its potential advantages when compared with other inotropes are unclear. To clarify the potential role of LS in this clinical setting randomized controlled trials on hemodynamic and mortality endpoints are needed.     

Levosimendan for patients with impaired left ventricular function undergoing cardiac surgery

The efficacy of levosimendan treatment for a low cardiac output status following cardiac surgery has not been established. Here, we review our initial experiences of the perioperative use of levosimendan. This study is a retrospective uncontrolled trial. Nine patients who underwent cardiac surgery, and developed a low cardiac output status resistant to conventional inotropic support, were given levosimendan. The mean preoperative ejection fraction was 35.2+/-3.4%. All patients were on concomitant inotropic agents and had previously undergone intra-aortic balloon pumping. Cardiac index increased immediately from 2.14+/-0.33 l/min/m(2) at baseline to 2.41+/-0.31 (P=0.02) at 1 h, rising to 2.67+/-0.43 (P<0.001) at 4 h after the loading dose was started. Similarly, the systemic vascular resistance index decreased from 2350+/-525 dynes/s/cm(-5)/m(2) at baseline to 1774+/-360 (P=0.002) at 4 h. In the case of all but one of the patients, either the dose of the concomitant inotropic support or the balloon pumping could be weaned down within 24 h after completion of the levosimendan infusion. No withdrawal of levosimendan was required. Levosimendan could constitute a new therapeutic option for postoperative low cardiac output.     

Hemodynamic effects of levosimendan following cardiac surgery

The hemodynamic effect of levosimendan was compared to that of dobutamine in a trial enrolling 30 adults undergoing scheduled cardiac surgery with cardiopulmonary bypass. Fifteen patients were randomly assigned to receive levosimendan in a single dose of 18 microg x kg(-1) followed in 15 to 20 minutes by start of infusion at a rate of 0.2 microg x kg(-1) min(-1) for 24 hours (levosimendan group). Another 15 randomized patients received dobutamine infused at a rate of 7.5 microg x kg(-1) min(-1). Hemodynamic parameters were measured before starting infusion of the drug and after 24 hours of treatment. Changes in the main hemodynamic parameters were as follows. In the levosimendan group heart rate (beats/min) was 87.15 (SD 10.22) at baseline and 87.91 (6.00) at 24 hours; mean arterial pressure (mm Hg) was 83.96 (10.57) at baseline and 86.41 (13.29) after 24 hours; cardiac index (L/min/m2) was 2.21 (0.23) at baseline and 2.53 (0.35) at 24 hours; systemic vascular resistance (dyn/sec(-1)/cm(-5)) was 1436.74 (311.48) at baseline and 1378.35 (320.68) at 24 hours. In the dobutamine group heart rate (beats/min) was 84.28 (2.18) at baseline and 96.02 (9.10) after 24 hours; mean arterial pressure (mm Hg) was 83.59 (9.05) at baseline and 74.29 (6.33) at 24 hours; cardiac index (L/min/m2) was 2.16 (0.28) at baseline and) 3.02 (0.34) at 24 hours; systemic vascular resistance (dyn/sec(-1)/cm(-5)) was 1578.93 (334.88) at baseline and 1136.68 (158.60) at 24 hours. We found that mean arterial pressure and both systemic and pulmonary vascular resistance decreased significantly in the levosimendan group (P < 0.05), but not in the dobutamine group. On the other hand, both heart rate and cardiac index increased in the levosimendan group only (P < 0.05). We conclude that levosimendan improves hemodynamic stability in patients who have undergone cardiac surgery and that it is a good alternative for treating postoperative low cardiac output syndrome.     

Levosimendan, a new positive inotropic drug, decreases myocardial infarct size via activation of K(ATP) channels

We tested the hypothesis that levosimendan, a new positive inotropic drug that activates adenosine triphosphate-regulated potassium (K(ATP)) channels in vitro, decreases myocardial infarct size in vivo. Myocardial infarct size was measured after a 60-min left anterior descending coronary artery occlusion and 3 h of reperfusion in dogs receiving either IV vehicle (0.9% saline) or levosimendan (24 microg/kg bolus followed by an infusion of 0.4 microg x kg(-1) x min(-1)) in the presence or absence of glyburide (a K(ATP) channel antagonist) pretreatment (100 microg/kg). Levosimendan increased (P < 0.05) the maximal rate of increase of left ventricular pressure and decreased myocardial infarct size from 24%+/-2% (control experiments) to 11%+/-2% of the left ventricular area at risk for infarction. Glyburide did not alter the hemodynamic effects of levosimendan but blocked levosimendan-induced reductions of infarct size. Subendocardial collateral blood flow was similar among groups. However, levosimendan increased subepicardial and midmyocardial collateral perfusion in the absence, but not in the presence, of glyburide. Levosimendan exerts cardioprotective effects via activation of K(ATP) channels at a dose that simultaneously enhances myocardial contractility. IMPLICATIONS: Levosimendan may be advantageous in patients requiring inotropic support who are also at risk of myocardial ischemia. Activation of adenosine triphosphate-regulated potassium channels during infusion of levosimendan may produce cardioprotective effects while simultaneously enhancing ventricular contractile function.     

Efficacy and safety of perioperative infusion of levosimendan in patients with compromised cardiac function undergoing open-heart surgery: importance of early use.

OBJECTIVE: Levosimendan is a promising new inotrope. We investigate the proper time for its infusion during or after open-heart surgery to avoid complications related with low-output syndrome and high dosage of inotropes. METHODS: Forty-five consecutive patients were randomised to receive levosimendan in addition to the conventional therapy, its infusion starting in the operating theatre (Group OT) or in the ICU (Group ICU) when low-output syndrome was certified and were consequently dependent on classical inotropic support and IABP. Levosimendan was infused at a rate of 0.1 microg/kg min without loading dose, the infusion being for at least 24h to a maximum 48 h. RESULTS: Levosimendan was well tolerated, with the simultaneous infusion of norepinephrine if required. Its efficacy was identical in both groups with improvement in the haemodynamic and functional status of patients (amelioration of stroke volume, cardiac index and mixed venous blood oxygen saturation, increase of left ventricular ejection fraction by echo study, de-escalation of traditional inotropes, subtraction of IABP and reduction in BNP plasma levels). The ICU stay and hospital stay were significantly decreased in patients of Group OT, compared to patients of Group ICU. Four patients died because of multiple organs dysfunction syndrome (MODS) due to sepsis (all patients of Group ICU). CONCLUSION: Levosimendan is a safe and efficient choice in the management of low-output syndrome during and after open-heart surgery. The shortening of hospitalisation and the trend for better outcome confirm its clear superiority when the infusion starts from the operating theatre.     

Levosimendan compared with dobutamine in low output patients

There are 2 studies which have investigated the hemodynamic efficacy of levosimendan compared to dobutamine in congestive heart failure patients. The first is a dose finding comparative 24-h infusion trial which included 95 NYHA II-III patients to different doses of levosimendan and 20 patients to dobutamine administered as a continuous, open-label infusion of 6 microg/kg/min. Efficacy and safety of levosimendan in severe low-output heart failure a randomized, double-blind comparison to dobutamine study compared the short- and long-term efficacy and safety of a single 24-hour infusion of levosimendan (n=103) with dobutamine (n=100) in hospitalised patients in acute heart failure. This double-blind, parallel-group, randomised trial showed that, irrespective of the aetiology of the heart failure, levosimendan produced significantly greater improvement in major determinants of cardiac function in heart failure patients compared to dobutamine. Levosimendan produced significantly greater haemodynamic improvements than dobutamine by significantly reduced mortality at 31 days compared with dobutamine; this reduction was maintained at 180 days. Levosimendan significantly increased the number of days alive and out of hospital, compared with dobutamine. It was better tolerated than dobutamine and fewer patients receiving levosimendan experienced arrhythmias and myocardial ischaemia, compared with dobutamine. Levosimendan produced haemodynamic responses that were unaffected by concomitant use of beta blockers.     

Experiences of levosimendan as an inotropic agent in conjunction with passive containment surgery

OBJECTIVES: Levosimendan is a calcium sensitizer with a positive inotropic effect without increasing oxygen consumption. We have evaluated the immediate effects of levosimendan on cardiac index when given peri-operatively to patients with dilated cardiomyopathy in conjunction with passive containment surgery. DESIGN: Ten patients with dilated cardiomyopathy undergoing passive containment surgery with the ACORN Cardiac Support Device, either as the sole procedure or in combination with other open heart surgery, were after anaesthesia induction given levosimendan as a bolus dose of 12 microg/kg followed by an infusion of 0.1microg/kg/min for 24 hours. Cardiac index were measured before extra corporal circulation, immediately after extra corporal circulation, at arrival to the intensive care unit and on post operative day 1. The need for inotropic support was recorded. RESULTS: Nine of ten patients were preoperatively in a low cardiac output situation. At postoperative day 1 there was a significant increase in cardiac index from 2.1+/-0.1 to 2.8+/-0.2. CONCLUSIONS: This study confirms the theoretical benefits of levosimendan judged by an immediate significant positive effect on cardiac index.     

Milrinone therapy in catecholamine-dependent critically ill patients with heart failure

BACKGROUND: Treatment with the PDE-III inhibitor milrinone improves hemodynamics in patients with heart failure. We examined whether therapy with milrinone is safe and effective in critically ill patients with catecholamine-dependent heart failure and whether treatment with milrinone facilitates weaning from prolonged catecholamine therapy. METHODS: Twenty adult patients with reduced left ventricular function and prolonged (7+/-4 days) catecholamine therapy in whom attempts at catecholamine weaning had failed were examined. Patients were prospectively randomised either to group A (addition of a fixed dose of 0.5 microg x kg(-1) x min(-1) milrinone to catecholamine therapy) or to group B (continued catecholamine therapy without milrinone). Dobutamine and norepinephrine treatment and fluid intake were titrated according to predefined hemodynamic goals. Hemodynamic parameters, fluid requirements and catecholamine dose were monitored. RESULTS: After 24 h of study treatment goup A showed a significant increase in cardiac index (2.2+/-0.4 1 min(-1) x m(-2) to 2.7+/-0.51 min(-1) x m(-2); P<0.005), a decrease in systemic vascular resistance (1,427+/-609 dyn x s x cm(-5) to 951+/-184 dyn x s x cm(-5); P<0.005), required lower doses of dobutamine (5.9+/-4.2 microg x kg(-1) x min(-1) to 2.2+/-3.3 microg x kg(-1) x min(-1); P<0.02), but showed a tendency for higher vasoconstrictor (0.14+/-0.16 microg x kg(-1) x min(-1) to 0.29+/-0.43 microg x kg(-1) x min(-1); P=n.s.) and fluid requirements (+1,404+/-2,257 ml/24 h to +2,508+/-1,873 ml/ 24 h; P=n.s.). No significant changes occurred in group B. Weaning from catecholamine therapy was more often achieved in group A and more milrinone treated patients were discharged alive from the ICU (80% vs. 30%; P<0.05). CONCLUSIONS: Milrinone improves central hemodynamics and may facilitate weaning from prolonged catecholamine support in critically ill patients with heart failure. Its administration in this subset of critically ill patients is safe, but eventually is associated with additional vasoconstrictor and fluid requirements.     

Levosimendan effect on spinal cord ischemia-reperfusion injury following aortic clamping

BACKGROUND AND AIM OF THE STUDY: The new calcium sensitizer, levosimendan, not only acts as a positive inotropic agent but also, vasodilates both venules and arterioles. The aim of this experimental study was to investigate whether levosimendan has protective effects on spinal cord ischemia-reperfusion injury. MATERIAL AND METHODS: Twelve New Zealand rabbits were enrolled in this study. In addition to the control group, levosimendan is administered to the experimental group with a loading dose of 12 microg/kg prior to ischemia over a 10-minute period, followed by an infusion of 0.2 microg/kg/min during the ischemia period (30-minutes). Following the neurologic evaluation at the 24th hour of reperfusion, lumbar spinal cords were removed in order to perform microscopic examination and malondialdehyde (MDA) and myeloperoxidase (MPO) measurements. RESULTS: The mean Tarlov score of the levosimendan group (3.25) was higher than the control group (0.7) (p< 0.05). MDA level was found significantly lower in the levosimendan group when compared with the control group as 1.6 +/- 0.4 nmol/gr and 189.3 +/- 43.6 nmol/gr respectively (p < 0.05). MPO level was also found statistically significant when we compared levosimendan group with the control group. It was calculated as 11.3 +/- 1.0 micro/gr tissue and 39.1 +/- 16.9 micro/gr in the levosimendan and the control groups (p< 0.05). Light microscopic examination was carried out with tissue samples in the 24th hour of the reperfusion. Levosimendan group had better preservation with the microscopic appearance with respect to the control group. CONCLUSION: Levosimendan exhibits an important protection by means of neurological outcome, histopathological, and biochemical analysis for the ischemia-reperfusion injury of the spinal cord following the aortic clamping.     

Experiences of levosimendan as an inotropic agent in conjunction with passive containment surgery

Objectives. Levosimendan is a calcium sensitizer with a positive inotropic effect without increasing oxygen consumption. We have evaluated the immediate effects of levosimendan on cardiac index when given peri-operatively to patients with dilated cardiomyopathy in conjunction with passive containment surgery. Design. Ten patients with dilated cardiomyopathy undergoing passive containment surgery with the ACORN Cardiac Support Device, either as the sole procedure or in combination with other open heart surgery, were after anaesthesia induction given levosimendan as a bolus dose of 12 µg/kg followed by an infusion of 0.1µg/kg/min for 24 hours. Cardiac index were measured before extra corporal circulation, immediately after extra corporal circulation, at arrival to the intensive care unit and on post operative day 1. The need for inotropic support was recorded. Results. Nine of ten patients were preoperatively in a low cardiac output situation. At postoperative day 1 there was a significant increase in cardiac index from 2.1±0.1 to 2.8±0.2. Conclusions. This study confirms the theoretical benefits of levosimendan judged by an immediate significant positive effect on cardiac index.     

The calcium sensitizer levosimendan and cardiac arrhythmias: an analysis of the safety database of heart failure treatment studies

BACKGROUND: Levosimendan is a calcium sensitizer that increases the contractility of the myofilaments and is considered not to affect cardiac electrophysiology. We assessed its potential to generate cardiac arrhythmias by analysing ECG recordings from clinical studies on intravenously administered levosimendan in heart failure patients. METHODS AND RESULTS: The database consisted of continuous 1-day recordings, of which 366 were during levosimendan and 142 during placebo comparison. Supraventricular (SVT) and ventricular tachycardia (VT) were defined as > or =3 premature complexes at a rate > or = 120/min. No difference appeared between levosimendan and control groups in the occurrence of atrial fibrillation (12% vs 13%), SVT (28% vs 30%), or VT (41% vs 44% of all recordings; all p = NS). Also the frequency of VT was similar (0.55 +/- 3.89 vs 0.20 +/- 1.08 episodes/h; p = NS). No torsade de pointes or sustained VT occurred. CONCLUSION: Short-term levosimendan therapy of heart failure showed no tendency to increase cardiac arrhythmias. Although assessing only surrogates of prognostically significant arrhythmias, the findings together with previously observed reduction of mortality in heart failure therapy studies support the presumption that levosimendan has an electrophysiologically neutral profile.     

Comparison of dopamine and dobutamine therapy during intraaortic balloon pumping for the treatment of postcardiotomy low-output syndrome

Treatment of postcardiotomy low-output syndrome includes intraaortic balloon pumping (IABP), volume loading, pharmacological afterload reduction, and stimulation with an inotropic agent. This study compares the effectiveness of combined nitroprusside and dopamine therapy and nitroprusside and dobutamine therapy in 12 patients requiring IABP postoperatively. Serial hemodynamic measurements were made before and during infusion of nitroprusside and after administration of the combined therapy (N = 6 in each group). Prior to pharmacological therapy, cardiac index was 1.47 +/- 0.31 L/min/m2 and systemic vascular resistance (SVR) was 3,114 +/- 1,350 dynes sec cm-5 in patients subsequently given dopamine, and 1.59 +/- 0.38 L/min/m2 and 2,661 +/- 405 dynes sec cm-5, respectively, in those given dobutamine. With infusion of nitroprusside, both groups showed significant reduction in SVR. Nitroprusside plus either inotropic agent resulted in augmentation of cardiac index and an additional reduction in SVR, both changes being greater in the group given dopamine. Larger doses of dobutamine than dopamine were needed to achieve similar hemodynamic improvement. We conclude that the addition of an inotropic agent to vasodilator therapy during IABP results in a greater increase in cardiac index and a greater decrease in afterload than a vasodilator alone. In addition to its beneficial effect on renal perfusion at the dose required to effect these improvements, dopamine appears a better inotropic agent than dobutamine for postcardiotomy low-output syndrome.     

Primary graft failure and Ca2+ sensitizers after heart transplantation

Primary organ failure after heart transplantation is a severe complication generally related to prolonged ischemia time, poor quality of the organ, or rejection. Ca(2+) sensitisers increase cardiac contractility without altering intracellular Ca(2+) levels. Our aim was to evaluate the influence of levosimendan in the therapy of primary failure after heart transplantation. Five patients presenting with reduced ejection fraction (EF<30%) and high dosed catecholamines after heart transplantation were treated with levosimendan (Simdax, Abbot GesmbH, Vienna, Austria) in a 24-hour continuous infusion (0.10 microg/kg*min) postoperatively. We assessed hemodynamic measurements including MAP, CVP, and PAP as well as heart function. Pharmacologic support with catecholamines could be halved at 24 hours and terminated in four of the patients 72 hours after levosimendan administration. Hemodynamics (MAP 70 +/- 11 vs 85 +/- 6 mm Hg; CI 2.5 +/- 0.4 vs 3.6 +/- 0.4 L/min/m(2)) and EF (28 +/- 10 vs 54 +/- 4%) improved at 48 hours after treatment. Acute graft failure after cardiac transplantation is associated with poor short- and long-term outcomes. Among our patients, levosimendan reduced the need for catecholamine support as well as improved ventricular performance.     

Home continuous positive inotropic infusion as a bridge to cardiac transplantation in patients with end-stage heart failure.

BACKGROUND: The clinical use of positive inotropic therapy at home in patients awaiting cardiac transplantation has not been reported since United Network for Organ Sharing (UNOS) regulations were changed to allow home infusions in Status 1B patients. METHODS: We observed 21 consecutive patients with UNOS 1B status during positive inotropic therapy at home. We used hemodynamic monitoring at the initiation of therapy to optimize dosing. We selected for home therapy patients with stable clinical status and improved functional capacity during inotropic treatment. Implantable cardioverter defibrillators were placed in all but 1 patient before discharge. RESULTS: Initial positive inotropic therapy included dobutamine in 12 patients (mean dose, 4.5 mcg/kg/min; range, 2.5-7.5 mcg/kg/min), milrinone in 8 patients (mean dose, 0.44 mcg/kg/min; range, 0.375-0.55 mcg/kg/min), and dopamine at a dose of 3 mcg/kg/min in 1 patient. Patients had improved functional capacity (New York Heart Association Class 3.7 +/- 0.1 to 2.4 +/- 0.2, p < 0.01), improved renal function (serum creatinine, 1.5 +/- 0.1 to 1.3 +/- 0.1, p < 0.01), improved resting hemodynamics, and decreased number of hospitalizations during positive inotropic infusion therapy when compared with pre-treatment baseline. Implantable cardioverter defibrillator discharges were infrequent (0.19 per 100 patient days of follow-up). Actuarial survival to transplantation at 6 and 12 months was 84%. CONCLUSIONS: Continuous positive inotropic therapy at home was safe and was associated with decreased health care costs in selected patients awaiting cardiac transplantation.     

Levosimendan in cardiac surgery

OBJECTIVE: Levosimendan is a new calcium sensitizer with inodilatory properties. There is growing clinical experience with levosimendan given to cardiac surgical patients. The aim of this report was to evaluate the effects of perioperative use of levosimendan in surgical patients with high perioperative risk, compromised left ventricular (LV) function, or difficulties in weaning from cardiopulmonary bypass (CPB). DESIGN: Case series. SETTING: Single-institution, university hospital. PARTICIPANTS: Patients undergoing cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Sixteen cardiac surgical patients received levosimendan infusion with a maximum duration of 29 hours. Eight were initiated preoperatively and 8 postoperatively. Coronary artery disease was the main operative indication in 10 of 16 cases, and 75% of the patients were high-risk patients. RESULTS: Continuous levosimendan infusion increased cardiac index significantly in both groups compared with preoperative baseline. Pulmonary capillary wedge pressure and systolic blood pressure did not change significantly. Norepinephrine and epinephrine were the most common concomitant vasoactive medications. Most importantly, weaning from CPB was successful in all patients even after failure to wean the patient with catecholamines. One high-risk patient in the preoperative group and 2 patients in the postoperative group died in the hospital. Another patient died during the 1-year follow-up. CONCLUSION: Levosimendan can be used for postoperative rescue therapy for patients difficult to wean from CPB. Also, elective preoperative initiation of levosimendan seems applicable to patients with high perioperative risk or compromised LV function.     

Levosimendan in cardiac surgery: current best available evidence

Recent upsurge in referral of patients with high perioperative risk or compromised left ventricular function for cardiac surgery has lead to an increasing use of pharmacologic support in the form of vasodilator and inotropic therapy to achieve improvement of tissue perfusion in the perioperative period or to support weaning from cardiopulmonary bypass. Traditionally, perioperatively used inotropic agents, epinephrine, dobutamine, and milrinone, are limited by significant increases in myocardial oxygen consumption, proarrhythmia, or neurohormonal activation. Levosimendan, a new inodilator for the treatment of decompensated heart failure, has also shown promise in elective therapy of cardiac surgical patients with high perioperative risk or compromised left ventricular function, as well as in rescue therapy of patients with difficult weaning from cardiopulmonary bypass. This review article briefly discusses the pharmacology of levosimendan and evaluates current best available evidence to assess the safety and efficacy of levosimendan usage in cardiac surgery.     

Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?

Levosimendan, is a new calcium sensitiser with 2 major effects. First, levosimendan acts as a positive inotropic agent by binding calcium dependently to cardiac troponin C. Second, levosimendan activates adenosine triphosphate-regulated potassium (K (ATP)) channels. Thus it has vasodilatory properties and cardioprotective effects at a dose enhancing myocardial contractility. These unique properties of levosimendan might be of great advantage in patients with myocardial ischemia simultaneously requiring inotropic support. The concept of perioperative inoprotection is presented in 6 patients with acute ischemia undergoing emergent cardiac surgery.     

Rolle von Levosimendan in der intensivmedizinischen Behandlung des myokardialen Pumpversagens

Levosimendan is a calcium sensitizer that is currently in the focus of intensive care medicine because it may be superior to standard inotropic agents in the treatment of acute myocardial insufficiency. The effects of levosimendan mainly depend on three predominant mechanisms: 1) positive inotropic effect by increasing the sensitivity of cardiac myofilaments to calcium ions, 2) vasodilatory effect by stimulation of adenosine triphosphate-sensitive potassium channels and 3) inhibition of phosphodiesterase-III. In a large number of experimental and clinical studies further possible indications for levosimendan have been described, e.g. cardioprotection during ischemia, cardiogenic shock, septic myocardial insufficiency and pulmonary hypertension. This review article critically summarizes the current scientific and clinical knowledge about levosimendan, its pharmacologic characteristics, mechanisms of action as well as indications and potential risks.     

Myocardial depression associated with pneumococcal septic shock reversed by levosimendan

Levosimendan is a myocardial calcium sensitiser and potassium-ATP channel opener Levosimendan has been used in critically ill patients in various conditions to support myocardial function as an inotrope, lusitrope and vasodilator. We report the use of levosimendan in a patient with invasive streptococcal septic shock.     

Septic shock: does adrenaline have a role as a first-line inotropic agent?

Fifteen adult patients, admitted to Baragwanath Hospital ICU with septic shock after adequate fluid loading and on no other inotropic agents, were given adrenaline in incremental doses. Oxygen transport and haemodynamic variables were monitored with each dose increment until a systolic blood pressure of 120 mmHg was obtained. This was reached on an average dose of adrenaline of 0.16 +/- 0.02 micrograms/kg/min. Mean arterial blood pressure increased by 22 +/- 2 mmHg mainly due to an increase in cardiac index (1 +/- 0.2 l/min/m2) and systemic vascular resistance index (130 +/- 41 dyn.s.cm.-5m-2) with a small increase in heart rate of 8 +/- 3 beats per minute. Oxygen delivery was increased with no significant increase in oxygen consumption and lactate levels increased. Adrenaline is therefore an effective initial inotropic agent. Patients may respond to lower doses than when used concurrently with other inotropic agents but there was still a significant dose variation in response. We cannot, however, exclude a deleterious effect on oxygen utilization.