The use of the novel calcium sensitizer levosimendan in critically ill patients

Levosimendan, a novel calcium sensitizer, enhances cardiac contractility by increasing myocyte sensitivity to calcium, and induces vasodilation. In this prospective observational study the haemodynamic effects of levosimendan in postoperative critically ill patients are reported. Twelve patients with the need for inotropic support were studied. One dose of levosimendan (12.5 mg) was administered at a rate of 0.1-0.2 microg kg(-1).min(-1), either alone or in addition to pre-existing inotropic therapy. Haemodynamic measurements were obtained at baseline, and at 3 h, 6 h, 12 h, and 24 h after the start of the levosimendan infusion. Levosimendan significantly increased cardiac output from (mean+/-SD) 4.3+/-0.91.min(-1) to 5.2+/-1.51 min(-1) after 24h (P=0.013), by increases in stroke volume (baseline 47+/-15 ml, after 24h 57+/-25 ml, P=0.05), as heart rate remained unchanged. Systemic vascular resistance decreased from 1239+/-430 dyn.sec.cm(-5) at baseline to 963+/-322 dyn.sec. cm(-5) at 24h (P<0.001). Pre-existing inotropic therapy present in ten patients remained unchanged or was reduced. In postoperative critically ill patients, infusion of levosimendan exerted favourable haemodynamic responses. Levosimendan increased cardiac output by increasing stroke volume, which might be attributed primarily to its inotropic properties. Due to its cyclic adenosine monophosphate independent positive inotropic effects, levosimendan may be of value as adjunctive therapy to other inotropic drugs in critically ill patients.     

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.     

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.     

The effect of milrinone for the shock patients after cardiac surgery

The effect of milrinone in the 16 postoperative shock patients of cardiovascular surgery was studied. The preoperative hemodynamic status were 12 of cardiogenic shock, 2 cases of chronic heart failure and 2 cases of unstable angina pectoris. The operative procedure were 8 cases of coronary artery bypass grafting, 4 cases of valvular surgery, 2 cases of closure of ventricular septal perforation, 2 cases of Bentall operation and 1 case of ascending aortic replacement. The postoperative hemodynamic status were 15 cases of cardiogenic shock, 10 cases of hemorrhagic shock and 1 case of septic shock. Continuous intravenous infusion of 0.5 microgram/kg/min without initial bolus loading was administered immediately after the entrance of the intensive care unit. Significant increase in the maximum blood pressure 3 hours after the infusion were observed (84 +/- 17 mmHg vs 94 +/- 12, p = 0.033). The maximum blood pressure was increased gradually until 24 hours after the infusion. Significant increase in the peripheral body temperature 3 hours after the infusion were observed (32.5 +/- 2.0 degrees C vs 35.9 +/- 1.1 degrees C, p = 0.001). The difference between the peripheral temperature and the central body temperature diminished until 24 hours after the infusion. No significant change in the central venous pressure, pulmonary arterial pressure, pulmonary and cardiac index wedge pressure were observed. No significant change in the platelet number was observed until 3 days after the infusion. Twenty patients (75%) were discharged. Four hospital deaths included 1 cardiac and 3 septic cause were seen. These data suggest that the administration of milrinone for the shock patients after cardiac surgery showed safe and that the continuous intravenous infusion of 0.5 microgram/kg/min without bolus loading showed effective for the recovery of the peripheral circulation.     

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.     

Vasopressin as a rescue vasopressor agent. Treatment of selected cardiogenic shock states

Vasodilatory shock is the most common form of shock in the critically ill patient. As a consequence of overwhelming and prolonged mediator production, vasodilatory shock can be the common final pathway of primary non-vasodilatory shock (e.g. cardiogenic or hypovolemic shock). A supplementary infusion of arginine vasopressin (AVP) showed beneficial effects on hemodynamics and potentially on the outcome in patients with vasodilatory shock due to sepsis or after major surgery. In this case series, successful administration of AVP in three surgical patients with primary cardiogenic shock forms is reported. The hemodynamic effects of AVP were comparable to those AVP-induced alterations described in septic shock and seem to be predominantly mediated by potent vasoconstriction and the facilitated reduction of higher, potentially toxic catecholamine doses. Thus, an AVP-induced decrease in heart rate and pulmonary arterial pressures may be particularly beneficial in patients with impaired cardiac function.     

Vasopressin als Reservevasopressor

Vasodilatory shock is the most common form of shock in the critically ill patient. As a consequence of overwhelming and prolonged mediator production, vasodilatory shock can be the common final pathway of primary non-vasodilatory shock (e.g. cardiogenic or hypovolemic shock). A supplementary infusion of arginine vasopressin (AVP) showed beneficial effects on hemodynamics and potentially on the outcome in patients with vasodilatory shock due to sepsis or after major surgery. In this case series, successful administration of AVP in three surgical patients with primary cardiogenic shock forms is reported. The hemodynamic effects of AVP were comparable to those AVP-induced alterations described in septic shock and seem to be predominantly mediated by potent vasoconstriction and the facilitated reduction of higher, potentially toxic catecholamine doses. Thus, an AVP-induced decrease in heart rate and pulmonary arterial pressures may be particularly beneficial in patients with impaired cardiac function.     

Impact of preoperative hemodynamic support on early outcome in patients assisted with paracorporeal Thoratec ventricular assist device

BACKGROUND: Mechanical circulatory support has become a well-established procedure for some patients with cardiogenic shock. However, patient selection and timing of implantation remains critical. This retrospective study was undertaken to identify preoperative predictors of survival in ICU of patients requiring mechanical circulatory support. METHODS: Between 1996 and 2006, 71 patients (61 men, 10 women, aged 41.6+/-12.2 years) with primary cardiogenic shock were assisted using the paracorporeal Thoratec VAD. Twenty-seven (38%) patients needed preoperative mechanical ventilation. Preoperative IV hemodynamic drug support included dobutamine in 63 (89%), vasopressors (adrenaline, noradrenaline or dopamine > or =5 microg/kg min) in 47 (66%), and intraaortic balloon counter-pulsation in 22 (31%) patients. Mean preoperative blood creatinine and total bilirubin levels were 162.2+/-72.4 micromol/l and 36.4+/-53.9 micromol/l, respectively. RESULTS: Fifty-six (79%) patients required biventricular and 15 (21%) left ventricular support. Patients were assisted for a mean duration of 73.1+/-93.6 days (extremes, 1-480 days). Twenty-five patients (35%) died while on support. Among these, 18 patients (25%) never recovered sufficiently to allow dismissal from ICU, and died after a mean of 15.4+/-14.3 days. Logistic regression identified preoperative IV adrenaline as sole predictor for ICU death (OR, 5.48; 95% CI, 1.45-20.7, p=0.012). CONCLUSIONS: The need for preoperative IV adrenaline therapy appeared to be the sole independent risk factor for death in ICU in patients assisted with the Thoratec paracorporeal VAD. This suggests that, besides hemodynamic and metabolic consequences of cardiogenic shock, preoperative activation of the inflammatory cascade could influence the prognosis of patients undergoing mechanical circulatory support.     

Dopamine may preserve the myocardial oxygen balance better than dobutamine when administered with milrinone

PURPOSE: To compare the hemodynamic effects of dopamine with those of dobutamine when administered with milrinone in patients undergoing non-cardiac surgery. METHODS: In 14 patients undergoing major surgery during anesthesia with isoflurane, milrinone (50 microgram*kg(-1) followed by 0.25 microgram*kg(-1)*min(-1)) was administered. Hemodynamic baseline values were assessed 50 min after continuous infusion of milrinone. Additional infusion of either dopamine or dobutamine, randomly selected, was started at the rate of 4 and later 8 microgram*kg(-1)*min(-1); each hemodynamic variable was measured 20 min after changing the infusion rate. One hour after ceasing the infusion of one catecholamine (dopamine or dobutamine), the other was infused at the rate of 4 and 8 microgram*kg(-1)*min(-1). RESULTS: Milrinone increased heart rate (HR), but decreased mean arterial pressure (MAP) and systemic vascular resistance (SVR) (P < 0.05 for each). Dopamine administered with milrinone significantly increased MAP and cardiac output (CO), whereas dobutamine significantly increased HR and CO, but decreased SVR. By comparison between dopamine and dobutamine administered at the rate of 8 microgram*kg(-1)*min(-1), there was a significant difference in HR, MAP, and SVR (P < 0.01, 0.01, and 0.05, respectively). CONCLUSION: Dopamine and dobutamine administered with milrinone induce different hemodynamic changes: dopamine increases MAP without affecting HR, whereas dobutamine increases HR. Our data suggest that the myocardial oxygen balance might be better preserved with dopamine than with dobutamine when administered with milrinone.     

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 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.     

Changes in circulating blood volume after infusion of hydroxyethyl starch 6% in critically ill patients

BACKGROUND: The cardiovascular response to a volume challenge with hydroxyethyl starch (HES) (200/0.5) 6% depends on the relation between the volume of HES 6% infused and the expansion of the blood volume in critically ill patients. However, only relatively limited data exist on the plasma expanding effect of infusion of HES 6% in critically ill patients. The purpose of the study was to evaluate the variation in the expansion of the circulating blood volume (CBV) in critically ill patients after infusion of 500 ml of colloid (HES (200/0.5) 6%) using the carbon monoxide method. METHODS: In 20 consecutive patients admitted to the ICU requiring mechanical ventilation and volume expansion, 500 ml of HES (200/0.5) 6% was infused. The CBV was measured immediately before the infusion, 10 min after completing the infusion and then hourly for 8 h. RESULTS: The median volume expansion immediately after infusion was 470 ml (range 270 ml to 840 ml). The corresponding values after 4 h and 8 h were 265 ml (range -30 ml to 460 ml) and 120 ml (range -210 ml to 360 ml), respectively. The increase in CBV was only statistically significant for 4 h. The coefficient of variation of the method for estimation of CBV was 3.6%. CONCLUSIONS: The large interindividual variation of the volume expansion after infusion of HES 6% in critically ill patients illustrates one of the difficulties in optimizing colloid therapy and interpretating the changes in hemodynamic variables after a colloid challenge.     

Selective inducible nitric oxide inhibition can restore hemodynamics, but does not improve neurological dysfunction in experimentally-induced septic shock in rats

In this study, we evaluated the time course of changes in inducible nitric oxide synthase (iNOS) in the brain by using the rat model of sepsis induced by cecal ligation and puncture (CLP) and examined whether selective iNOS inhibition can prevent the hemodynamic and neurological changes induced by sepsis. Male Wistar rats were randomly divided into four groups: control, sham, CLP, and CLP + the selective iNOS inhibitor L-N6-(1-iminoethyl)-lysine (L-NIL). Septic shock was induced in the rats by CLP under pentobarbital anesthesia, and then we measured hemodynamic variables, neurological indicators, blood gases, plasma levels of nitrate/nitrite (an indicator of the biosynthesis of NO), and brain iNOS activity and nitrotyrosine levels after 1, 6, 12, and 24 h. Plasma nitrite was increased at 12 and 24 h in the CLP group. The activity of iNOS in the brain was increased at 12 and 24 h after CLP (at 12 h: control, 0.3 +/- 0.05; sham, 0.3 +/- 0.1; CLP, 1.3 +/- 0.08*; CLP + L-NIL, 0.33 +/- 0.1 fmol x mg(-1) x min(-1); at 24 h: control, 0.27 +/- 0.08; sham, 0.31 +/- 0.1; CLP, 1.0 +/- 0.3*; CLP + L-NIL, 0.34 +/- 0.1 fmol x mg(-1) x min(-1); mean +/- SD; *P < 0.05). Brain nitrotyrosine was increased at 24 h after CLP (at 24 h: control, 6.7 +/- 0.4; sham, 6.7 +/- 0.5; CLP, 11.2 +/- 2.8*; CLP + L-NIL, 7.52 +/- 0.5 densitometric units; means +/- SD; *P < 0.01). In contrast, in both the CLP and CLP + L-NIL groups, the consciousness reflex was significantly decreased at 24 h after CLP. Selective iNOS inhibition restored the hemodynamic changes induced by sepsis but could not improve neurological dysfunction.     

Clonidine Modulation of Hemodynamic and Catecholamine Responses Associated with Hypoxia or Hypercapnia in Dogs

Background: Hypoxia or hypercapnia elicits cardiovascular responses associated with increased plasma catecholamine concentrations, whereas clonidine, an alpha2 -adrenergic agonist, decreases plasma catecholamine concentrations. The authors examined whether systemic clonidine administration would alter the hemodynamic and catecholamine responses to hypoxia or hypercapnia in anesthetized dogs.

Methods: Pentobarbital-anesthetized dogs whose lungs were mechanically ventilated were instrumented for measurement of mean arterial pressure, heart rate, mean pulmonary artery pressure, right atrial pressure, cardiac output, left ventricular end-diastolic pressure, and the peak of first derivative of left ventricular pressure. The dogs were randomly assigned to receive an intravenous bolus injection of 10 micro gram/kg clonidine followed by continuous infusion at a rate of 1 micro gram *symbol* kg sup -1 *symbol* min sup -1 (clonidine-10 group, n = 7), an intravenous bolus injection of 5 micro gram/kg clonidine followed by continuous infusion at a rate of 0.5 micro gram *symbol* kg sup -1 *symbol* min sup -1 (clonidine-5 group, n = 7), or an equivalent volume of 0.9% saline (control group, n = 7). Each dog underwent random challenges of hypoxia (PaO2 30, 40, and 50 mmHg) and hypercapnia (PaCO sub 2 60, 80, and 120 mmHg). Measurements of hemodynamic and plasma norepinephrine and epinephrine concentrations were made during each period of hypoxia or hypercapnia, and measurements of plasma clonidine concentrations were made after the loading dose of clonidine and the first and the second exposure of hypoxia or hypercapnia.

Results: Although significant increases from prehypoxic values in mean arterial pressure (39+/-10 mmHg) and plasma norepinephrine (291+/-66 pg/ml) and epinephrine (45+/-22 pg/ml) concentrations were noted during hypoxia of PaO2 30 mmHg in the control group (P < 0.05), such changes were absent in both clonidine groups. During hypercapnia of PaCO2, 120 mmHg, changes from prehypercapnic values in mean arterial pressure, mean pulmonary artery pressure, the peak of first derivative of left ventricular pressure, and plasma norepinephrine and epinephrine concentrations in the clonidine-10 and clonidine-5 groups were significantly less than those in the control group. Plasma clonidine concentrations in the clonidine-10 and clonidine-5 groups were 16.8+/-1.7 and 8.9+/-1.0, 42.5+/- 2.9 and 21.5+/-1.5, and 51.1+/-3.2 and 26.7+/- 1.0 ng/ml after the loading dose of clonidine and the first and the second exposure of hypoxia or hypercapnia, respectively.     

Efficacy of phosphodiesterase inhibitor enoximone in management of postcardiotomy cardiogenic shock.

The efficacy of the phosphodiesterase inhibitor enoximone for reversal of severe postcardiotomy low cardiac output syndrome was investigated in 13 cases of cardiogenic shock refractory to conventional treatment consisting of beta-adrenergic agonists (n = 13) combined with vasodilators (n = 7), and intra-aortic balloon counterpulsation (n = 5). Following a bolus of 1 mg/kg enoximone, cardiac and stroke volume indices increased from 1.56 +/- 0.27 l/min/m2 and 16.3 +/- 3.3 ml/m2, respectively, to 2.72 +/- 0.67 and 27.8 +/- 7.1 (both p < 0.001). Mean arterial pressure fell, from 77 +/- 11 to 68 +/- 9 mmHg (p < 0.05), as did atrial filling pressures (LAP and RAP), LAP from 21.3 +/- 5.5 to 15.9 +/- 2.9 and RAP from 16.6 +/- 2.3 to 13.7 +/- 2.1 mmHg (both p < 0.01). The heart rate rose by only 5%. Enoximone therapy was maintained by a continuous infusion (5-7.5 micrograms/kg/min) for 40.6 +/- 8.6 hours (range 14-92). All hemodynamic parameters remained stable throughout treatment. Six patients died of sepsis and/or multiorgan failure but seven were discharged from hospital. Enoximone thus improved hemodynamic performance significantly in cardiogenic shock after open-heart surgery. It also has proved valuable in cardiac failure when conventional therapy was unsuccessful.     

Sympathetic neural activation evoked by mu-receptor blockade in patients addicted to opioids is abolished by intravenous clonidine

BACKGROUND: Mu-opioid receptor blockade by naloxone administered for acute detoxification in patients addicted to opioids markedly increases catecholamine plasma concentrations, muscle sympathetic activity (MSA), and is associated with cardiovascular stimulation despite general anesthesia. The current authors tested the hypothesis that the alpha2-adrenoceptor agonist clonidine (1) attenuates increased MSA during mu-opioid receptor blockade for detoxification, and (2) prevents cardiovascular activation when given before detoxification. METHODS: Fourteen mono-opioid addicted patients received naloxone during propofol anesthesia. Clonidine (10 microg x kg(-1) administered over 5 min + 5 microg x kg(-1) x h(-1) intravenous) was infused either before (n = 6) or after (n = 6) naloxone administration. Two patients without immediate clonidine administration occurring after naloxone administration served as time controls. Muscle sympathetic activity (n = 8) in the peroneal nerve, catecholamine plasma concentrations (n = 14), arterial blood pressure, and heart rate were assessed in awake patients, during propofol anesthesia before and after mu-opioid receptor blockade, and after clonidine administration. RESULTS: Mu-receptor blockade markedly increased MSA from a low activity (burst frequency: from 2 burst/min +/- 1 to 24 +/- 8, means +/- SD). Similarly, norepinephrine (41 pg/ml +/- 37 to 321 +/- 134) and epinephrine plasma concentration (13 pg/ml +/- 6 to 627 +/- 146) significantly increased, and were associated with, increased arterial blood pressure and heart rate. Clonidine immediately abolished both increased MSA (P < 0.001) and catecholamine plasma concentrations (P < 0.001). When clonidine was given before mu-opioid receptor blockade, catecholamine plasma concentrations and hemodynamic variables did not change. CONCLUSIONS: Administration of the alpha2-adrenoceptor agonist clonidine decreases both increased MSA and catecholamine plasma concentrations observed after mu-opioid receptor blockade for detoxification. Furthermore, clonidine pretreatment prevents the increase in catecholamine plasma concentration that otherwise occurs during mu-opioid receptor blockade.     

Hemodynamic effects of high-frequency jet ventilation in patients with and without circulatory shock

Nineteen critically ill patients with acute respiratory failure were studied to compare the hemodynamic effects of continuous positive-pressure ventilation (CPPV) and high-frequency jet ventilation (HFJV) at comparable levels of alveolar ventilation. Patients were divided into three groups: Group 1 included seven patients without circulatory shock in whom mean airway pressure (Paw) was slightly higher during CPPV than during HFJV (17.3 +/- 3.0 vs. 13.0 +/- 2.9 mmHg); Group 2 included six patients without circulatory shock in whom HFJV and CPPV were compared at the same level of Paw (19.2 +/- 5.0 mmHg); Group 3 included seven patients with circulatory shock in whom HFJV and CPPV were compared at the same level of Paw (16.0 +/- 3.9 mmHg). The following respiratory frequencies were used in HFJV: Group 1, 200 +/- 76 beats/min; Group 2, 238 +/- 103 beats/min; Group 3, 286 +/- 149 beats/min. In all patients comparable levels of PaCO2 were obtained with CPPV and HFJV. In Group 1 patients, mean arterial pressure, cardiac index, and stroke index were significantly higher during HFJV. In Group 2 patients, no significant difference was found between HFJV and CPPV. In Group 3 patients, the following hemodynamic variables were significantly higher during HFJV: mean arterial pressure (71 +/- 24 vs. 84 +/- 23 mmHg), cardiac index (3.6 +/- 1 vs. 4.1 +/- 1.41 X min-1 X m-2), and oxygen delivery (403 +/- 93 vs. 471 +/- 124 ml X min-1 X m-2).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fentanyl and sufentanil anesthesia revisited: how much is enough?

This study was undertaken to determine if fentanyl and sufentanil could produce dose-related suppression of hemodynamic and hormonal responses to surgical stimulation. Eighty patients scheduled for elective CABG were studied in two consecutive protocols: protocol I was a randomized double-blind study of 40 patients who received a single dose of fentanyl (50 or 100 micrograms/kg) or sufentanil (10, 20, or 30 micrograms/kg). Hemodynamic measurements and hormonal concentrations (renin, aldosterone, cortisol, and catecholamines) were determined before and after induction and after intubation and sternotomy. Protocol II was an open randomized study of 40 patients who received sufentanil in one of four doses: 30 micrograms/kg as a single dose, 10 micrograms/kg plus infusion 0.05 microgram.kg-1.min-1, 20 micrograms/kg plus infusion 0.1 microgram.kg-1.min-1, or 40 micrograms/kg plus infusion 0.2 microgram.kg-1.min-1. Hemodynamic measurements and plasma sufentanil and catecholamine concentrations were determined before and after induction and after intubation, sternotomy, and aortic cannulation. Both protocols defined a hemodynamic response as a 15% or more increase in systolic blood pressure (SBP) from control and a hormonal response 50% or more increase over control. During protocol I, 18 patients had a hemodynamic response (average increase in SBP 22.6 +/- 2%) and 35 patients had a total of 59 hormonal responses. During protocol II, 24 patients had a hemodynamic response (average increase in SBP - 31 +/- 3%) and there were 15 catecholamine responses. There were no differences between dose groups in either protocol. It was concluded that in these dose ranges, suppression of hemodynamic or hormonal stress responses is not related to opioid dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

延迟快速复苏对烧伤休克循环影响的临床研究

目的探讨在烧伤延迟复苏情况下,如何迅速纠正休克.方法通过对20例烧伤面积大于40%TBSA、因延迟复苏导致休克的患者,进行延迟快速复苏.观察休克期液体出入量、动咏压(BP)、肺动脉压(PAP)、肺动脉楔状压(PAWP)、中心静脉压(CVP)、心输出量(CO)、肺血管阻力(PVR)、外周血管阻力(SVR)、氧供应(DO2)、氧消耗(VO2)、氧摄取率(O2ext)、乳酸(LA)及碱缺失(BD)等血流动力学和氧代谢指标的变化.结果快速补液后2h内输入液体占“第一个24h公式计算量”的(38.8±6.1)%,如果加上院外补液量则占“第一个24h公式计算量”的(48.3±5.0)%.第一个24h实际补入量占“第一个24h公式计算量”的(131.4±14.3)%;第二个24h实际补入量占“第二个24h公式计算量”的(103.2±7.2)%.快速补液后,尿量大幅增加,CO显著升高,DO2增强,SVR、LA、BD大幅下降,PVR虽大幅升高,但PAWP、PAP和CVP并未超过正常.结论在严密血流动力学监护下,烧伤后延迟复苏初期加快补液速度是可行且有益的,烧伤休克的延迟复苏需要显著增加补液量.指导休克延迟快速复苏应以监护心输出量及PAP、PAWP、CVP等血流动力学指标为主,辅以血中LA、BD水平及尿量变化等临床指标的监测.     

Scandinavian SSAI clinical practice guideline on choice of inotropic agent for patients with acute circulatory failure

Background

Adult critically ill patients often suffer from acute circulatory failure and those with low cardiac output may be treated with inotropic agents. The aim of this Scandinavian Society of Anaesthesiology and Intensive Care Medicine guideline was to present patient‐important treatment recommendations on this topic.

Methods

This guideline was developed according to GRADE. We assessed the following subpopulations of patients with shock: (1) shock in general, (2) septic shock, (3) cardiogenic shock, (4) hypovolemic shock, (5) shock after cardiac surgery, and (6) other types of shock, including vasodilatory shock. We assessed patient‐important outcome measures, including mortality and serious adverse reactions.

Results

For all patients, we suggest against the routine use of any inotropic agent, including dobutamine, as compared to placebo/no treatment (very low quality of evidence). For patients with shock in general, and in those with septic and other types of shock, we suggest using dobutamine rather than levosimendan or epinephrine (very low quality of evidence). For patients with cardiogenic shock and in those with shock after cardiac surgery, we suggest using dobutamine rather than milrinone (very low quality of evidence). For the other clinical questions, we refrained from giving any recommendations or suggestions.

Conclusions

We suggest against the routine use of any inotropic agent in adult patients with shock. If used, we suggest using dobutamine rather than other inotropic agents for the majority of patients, however, the quality of evidence was very low, implying high uncertainty on the balance between the benefits and harms of inotropic agents.