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PubMed1999

Antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep.

BACKGROUND: alpha2-Adrenergic agonists produce analgesia primarily by a spinal action and hypotension and bradycardia by actions at several sites. Clonidine is approved for epidural use in the treatment of neuropathic pain, but its wider application is limited by hemodynamic side effects. This study determined the antinociceptive and hemodynamic effects of a novel alpha2-adrenergic agonist, MPV-2426, in sheep. METHODS: Forty sheep of mixed Western breeds with indwelling catheters were studied. In separate studies, antinociception to a mechanical stimulus, hemodynamic effects, arterial blood gas tensions, cerebrospinal fluid pharmacokinetics, and spinal cord blood flow was determined after epidural, intrathecal, and intravenous injection of MPV-2426. RESULTS: MPV-2426 produced antinociception with greater potency intrathecally (ED50 = 49 microg) than epidurally (ED50 = 202 microg), whereas intravenous administration had no effect. Intrathecal injection, in doses up to three times the ED95, failed to decrease systemic or central arterial blood pressures or heart rate, whereas larger doses, regardless of route, increased systemic arterial pressure. Bioavailability in cerebrospinal fluid was 7% after epidural administration and 0.17% after intravenous administration. Intrathecal MPV-2426, in an ED95 dose and three times this dose, produced a dose-independent reduction in thoracic and lumbar spinal cord blood flow. CONCLUSIONS: MPV-2426 shares many characteristics of other alpha2-adrenergic agonists examined in sheep, but differs from clonidine and dexmedetomidine by lack of antinociception and minimal reduction in oxygen partial pressure after large intravenous and epidural injections. No hemodynamic depression was observed after intrathecal injection at antinociceptive doses. These results suggest this compound may be an effective spinal analgesic in humans with less hypotension than clonidine, although its relative potency to cause sedation was not tested in this study.

Adrenergic alpha-2 Receptor Agonists↗
PubMed2000

Hemodynamic effects of synchronized high-frequency jet ventilation compared with low-frequency intermittent positive-pressure ventilation after myocardial revascularization.

BACKGROUND: The purpose of this prospective study was to examine the effect on cardiac performance of selective increases in airway pressure at specific points of the cardiac cycle using synchronized high-frequency jet ventilation (sync-HFJV) delivered concomitantly with each single heart beat compared with controlled mechanical ventilation in 20 hemodynamically stable, deeply sedated patients immediately after coronary artery bypass graft. METHODS: Five 30-min sequential ventilation periods were used interspersing controlled mechanical ventilation with sync-HFJV twice to control for time and sequencing effects. Sync-HFJV was applied using a driving pressure, which generated a tidal volume resulting in gas exchanges close to those obtained on controlled mechanical ventilation and associated with the maximal mixed venous oxygen saturation. Hemodynamic variables including cardiac output, mixed venous oxygen saturation and vascular pressures were recorded at the end of each ventilation period. RESULTS: The authors found that in 20 patients, hemodynamic changes induced by controlled mechanical ventilation and by sync-HFJV were similar. Cardiac index did not change (mean +/- SD for controlled mechanical ventilation: 2.6 +/- 0.7 l x min(-1) x m(-2); for sync-HFJV: 2.7 +/- 0.7 l x min(-1) x m(-2); P value not significant). This observation persisted after stratification according to baseline left-ventricular contractility, as estimated by ejection fraction. CONCLUSIONS: The authors conclude that after coronary artery bypass graft, if gas-exchange values are maintained within normal range, sync-HFJV does not result in more favorable hemodynamic support than controlled mechanical ventilation. These findings contrast with the beneficial effects of sync-HFJV, resulting in marked hypocapnia, on cardiac performance observed in patients with terminal left-ventricular failure.

Adult↗
PubMed1995

Nonoperative management of blunt hepatic trauma is the treatment of choice for hemodynamically stable patients. Results of a prospective trial.

BACKGROUND: A number of retrospective studies recently have been published concerning nonoperative management of minor liver injuries, with cumulative success rates greater than 95%. However, no prospective analysis that involves a large number of higher grade injuries has been reported. The current study was conducted to evaluate the safety of nonoperative management of blunt hepatic trauma in hemodynamically stable patients regardless of injury severity. METHODS: Over a 22-month period, patients with blunt hepatic injury were evaluated prospectively. Unstable patients underwent laparotomies, and stable patients had abdominal computed tomography (CT) scans. Those with nonhepatic operative indications underwent exploration, and the remainder were managed nonoperatively in the trauma intensive care unit. This group was compared with a hemodynamically matched operated cohort of blunt hepatic trauma patients (control subjects) who had been prospectively analyzed. RESULTS: One hundred thirty-six patients had blunt hepatic trauma. Twenty-four (18%) underwent emergent exploration. Of the remaining 112 patients, 12 (11%) failed observation and underwent celiotomy--5 were liver-related failures (5%) and 7 were nonliver related (6%). Liver related failure rates for CT grades I through V were 20%, 3%, 3%, 0%, and 12%, respectively, and rates according to hemoperitoneum were 2% for minimal, 6% for moderate, and 7% for large. The remaining 100 patients were successfully treated without operation--30% had minor injuries (grades I-II) and 70% had major (grades III-V) injuries. There were no differences in admission characteristics between nonoperative success or failures, except admission systolic blood pressure (127 vs. 104; p < 0.04). Comparing the nonoperative group to the control group, there were no differences in admission hemodynamics or hospital length of stay, but nonoperative patients had significantly fewer blood transfusions (1.9 vs. 4.0 units; p < 0.02) and fewer abdominal complications (3% vs. 11%; p < 0.04). CONCLUSIONS: Nonoperative management is safe for hemodynamically stable patients with blunt hepatic injury, regardless of injury severity. There are fewer abdominal complications and less transfusions when compared with a matched cohort of operated patients. Based on admission characteristics or CT scan, it is not possible to predict failures; therefore, intensive care unit monitoring is necessary.

Adult↗
PubMed1998

Hemodynamic effects of the laparoscopic pneumoperitoneum during sepsis in a porcine endotoxic shock model.

OBJECTIVE: The authors compared the hemodynamic effects of laparoscopic intervention with conventional laparotomy in an endotoxic shock model in the pig. SUMMARY BACKGROUND DATA: Laparoscopic techniques are being applied more frequently to severely ill patients to evaluate potential abdominal sources of sepsis. Although hemodynamic effects of laparoscopy are minimal in healthy patients, recent studies have shown more significant changes in patients with chronic cardiopulmonary disease. It is unclear whether these effects are applicable to acutely septic patients. METHODS: Twelve domestic pigs received intravenous lipopolysaccharide (LPS) injection and underwent surgical abdominal exploration using either laparoscopy or conventional laparotomy. For baseline comparison, four pigs underwent exploratory laparoscopy without intravenous LPS injection. Hemodynamic measurements and blood gas analyses were obtained using Swan-Ganz and arterial catheters. RESULTS: After LPS exposure, animals undergoing laparoscopic evaluation were significantly more hypercarbic (p < 0.01) and acidotic (p < 0.01) than those undergoing conventional laparotomy. Their mean pulmonary arterial pressure and pulmonary vascular resistance were greater as well (not significant). The cardiac index (p < 0.05) and stroke volume (p < 0.05) were decreased in the laparoscopic group. Their oxygen delivery was decreased and oxygen consumption increased, although these were not significantly different from those of the laparotomy group. The degree of acidosis was highly correlated with the cardiac index (correlation coefficient, r = 0.82). CONCLUSIONS: Animals exposed to LPS tolerate laparoscopy but with significant hemodynamic compromise. Much of this effect seems to be mediated by a cardiodepressive effect of acidosis. This study suggests that laparoscopic intervention, when used in septic patients, should be used with caution.

Animals↗
PubMed1994

Newer thinking on the hemodynamics of hypertension.

For more than 30 years there has been general agreement that in the established phase of essential hypertension, the cardinal hemodynamic disturbance is an increased total peripheral resistance with cardiac output normal during rest, but subnormal during exercise. However, there are still different opinions about the hemodynamics in the starting phase of essential hypertension. Several studies from 1993--mainly performed in the offspring of hypertensive parents--reported high as well as low cardiac index values, depending on the patient selection and the methods used. Irrespective of whether the early phase of essential hypertension is caused primarily by increased cardiac output or increased total peripheral resistance, an increased sympathetic activity is usually held responsible for either hemodynamic disturbance. Simultaneous recordings of central and regional hemodynamics and sympathetic nerve traffic in young subjects with mild hypertension did show increased cardiac output, reduced calf blood flow, and increased nerve traffic as the characteristic features. However, recent studies in subjects with borderline hypertension have shown that if the subjects were aware of having hypertension, they showed higher blood pressure and higher reactivity to mental stress and cold-pressor tests than uninformed subjects with similar blood pressures. With respect to regional circulation, studies have shown that the coronary reserve is reduced in early hypertension, and also in subjects without left ventricular hypertrophy. The role of the endothelium in the regulation of blood flow has attracted great interest. Abnormalities in the production of vasoconstricting and vasodilating substances from the endothelial cells may be at least partially responsible for the increased vascular resistance characteristic of essential hypertension.

Arousal↗
PubMed2000

Noninvasive assessment of hemodynamics: an emphasis on bioimpedance cardiography.

Evaluation of the hemodynamic response in heart failure is a useful adjunct in clinical management. Invasive monitoring has been the accepted gold standard of hemodynamic assessment but carries with it significant associated risks. Noninvasive hemodynamic assessment in heart failure previously has been either unreliable or difficult to obtain. Bioimpedance relies on the proportional change in the conduction of alternating current applied across the thorax as a function of blood volume in the heart and great vessels. Stroke volume, cardiac output, thoracic fluid content, and measures of diastolic function can be determined with bioimpedance. Impedance cardiography is becoming an accepted method for safe, reliable, and reproducible assessment of hemodynamics in heart failure.

Cardiography, Impedance↗
PubMed1981

Hemodynamic effects of inotropes during hypothermia and rapid rewarming.

The hemodynamic effects of propranolol, lidocaine, and dopamine were studied in anesthetized, mechanically ventilated dogs, cooled to 25 degrees C with a venovenous shunt through a heat exchanger. After 1 h at 25 degrees C, the shunt was converted to an arteriovenous shunt which remained functional until the study was completed. Before rewarming, the authors treated each group of 8 dogs with intravenous doses of the drugs: group 1: 10 ml saline as control; group 2: propranolol 0.3 mg/kg; group 3: 50 mg lidocaine initially, followed with continuous infusion of 40-50 microgram/kg.min; group 4: dopamine infusion at 12 microgram/kg.min; and group 5: lidocaine as in group 3 and dopamine as in group 4. For the dopamine-treated groups, 2 min of infusion was allowed; in all other groups, 5 min elapsed after injection before the hemodynamic data were recorded. The hemodynamic data were collected at esophageal temperatures of 25, 30, and 37 degrees C. The findings were: (1) hypothermia impaired cardiovascular function; (2) lidocaine and propranolol had minimal hemodynamic effects during hypothermia; lidocaine was physiologically more desirable than propranolol; (3) dopamine, alone or combined with lidocaine, reversed the cardiovascular depression from hypothermia; the improvement was equivalent to rewarming by as much as 5 degrees C; and (4) at the completion of rewarming, cardiovascular recovery was more complete with dopamine/lidocaine-treated animals compared to untreated and propranolol-treated animals. Based on these findings, these inotropes appear to be safe adjuncts to resuscitation during hypothermia.

Animals↗
PubMed1982

Hemodynamic response to changes in ventilatory patterns in patients with normal and poor left ventricular reserve.

Hemodynamic effects of controlled mechanical ventilation (CMV), intermittent mandatory ventilation (IMV), and intermittent mandatory ventilation with 5 cm H20 PEEP (IMV 5 peep) were studied in 20 patients after aortocoronary bypass surgery. Significant increases in cardiac index (CI) and stroke volume index (SI) (p less than 0.01) resulted in patients with normal left ventricular end-diastolic pressure (LVEDP) and ejection fraction (EF) changing from CMV to IMV. With a change from IMV to IMV 5 peep, the CI and SI returned to CMV values. However, in patients with increased LVEDP with an EF of less than 0.6, suggesting poor ventricular function and reserve, when the mode of ventilation was changed from CMV to IMV, right atrial pressure (RAP) and pulmonary artery occlusion pressure (PAOP) significantly increased (p less than 0.01) with an associated significant decrease in mean arterial pressure (MAP), CI, SI (p less than 0.01). When these patients were placed on IMV 5 peep, the hemodynamic variables returned to the values obtained during CMV. We conclude that changing from CMV to IMV has salutory effects on the patient's hemodynamic values with normal left ventricular function. But in patients with failing left ventricle, volume overload of right ventricle which occurs with the institution of spontaneous respiration during IMV has deleterious effects on the hemodynamic variables. These deleterious effects can be effectively negated by the application of IMV 5 peep.

Blood Pressure↗
PubMed1984

Clinical evaluation compared to pulmonary artery catheterization in the hemodynamic assessment of critically ill patients.

Although pulmonary artery (PA) catheterization is frequently employed in the management of critically ill patients, there is little documentation that the information obtained alters patient management. This study evaluated prospectively this question in 103 PA catheterizations. Before catheterization, physicians were asked to predict the range of several hemodynamic variables, the presumed diagnosis, and their plan for therapy. After catheterization, each chart was reviewed. The hemodynamics at the time of catheterization and therapy within 8 h of catheterization were noted. Pulmonary artery occlusive (wedge) pressure (WP) was correctly predicted 30% of the time. Cardiac output, systemic vascular resistance (SVR), and right atrial pressure (RAP) were correctly predicted approximately 50% of the time. There was no significant difference in the ability to predict hemodynamics of subgroups with either hypotension or impaired oxygenation. After catheterization, planned therapy was altered in 58% of the cases. Unanticipated therapy was added in 30% of the cases. This study documents the difficulty of predicting accurately hemodynamics based solely on clinical evaluation. Thus, the information obtained by catheterization often leads to alterations in the therapeutic plan. We suggest that PA catheterization is both indicated and useful in the management of critically ill patients.

Blood Pressure↗
PubMed1984

Hemodynamic alterations in canine acute lung injury induced with N-nitroso-N-methylurethane.

Acute alveolar injury induced by subcutaneous injection of N-nitroso-N-methylurethane (NNNMU) closely resembles the pathology of human adult respiratory distress syndrome (ARDS). However, its effects on cardiovascular function have not been evaluated. We measured hemodynamic variables and venous admixture (Qsp/Qt at FIO2 0.21) and shunt fraction (Qsp/Qt at FIO2 1.0) in 7 dogs. The measurements were repeated when a single subcutaneous injection of 8.0 mg/kg NNNMU decreased PaO2 on room air to 40 torr (phase I) and 30 torr (phase II). Within 5 to 7 days after injection, PaO2 decreased to 40 torr, Qsp/Qt at FIO2 0.21 increased from 0.18 to 0.70, Qsp/Qt at FIO2 1.0 increased to 0.55, and pulmonary vascular resistance index (PVRI) increased from 213 +/- 37 to 407 +/- 142 dyne X sec/cm5 X m2 (p less than .05). However, a decrease in mean arterial pressure (MAP) from 153 +/- 16 to 131 +/- 32 mm Hg was the only significant hemodynamic change. At phase II, decreased systemic vascular resistance index (SVRI) was the only significant hemodynamic alteration. We conclude that single subcutaneous injection of NNNMU produces hemodynamic and pulmonary dysfunction similar to that seen in human ARDS. This acute lung-injury model may be useful for evaluating different ARDS therapies.

Animals↗
PubMed1990

Renal hemodynamics and prostaglandin E2 excretion in a nonhuman primate model of septic shock.

The mechanisms responsible for renal insufficiency in septic shock (SS) have not been well characterized. We therefore investigated renal hemodynamics and the renal excretion of prostaglandin E2 (PGE2) in a nonhuman primate model of severe, low systemic vascular resistance (SVR) SS. In 18 cynomolgus monkeys, SS was induced by an infusion of 3 x 10(10) live Escherichia coli per kg; five saline-treated animals served as nonseptic controls. Systemic and renal hemodynamics, and urine PGE2 concentrations were determined over the 3 h after the induction of sepsis. The septic group demonstrated a significant (p less than .001) and sustained depression in both mean arterial pressure and SVR. Septic animals also had significantly lower effective renal plasma flow (ERPF) (p less than .01) and glomerular filtration rate (GFR) (p less than .01) compared to controls. Furthermore, the renal hemodynamic response to SS was biphasic, with significant increases in ERPF and GFR in the second hour postsepsis, followed by a pronounced decrease in the third postseptic hour. The septic group also demonstrated an increase in the renal excretion of PGE2 (p less than .001) that was temporally associated with the transient recovery in renal hemodynamics during the second postseptic hour. These sepsis-induced renal alterations may be important in the pathogenesis of renal insufficiency complicating clinical SS.

Acute Kidney Injury↗
PubMed1990

Hemodynamic status susceptible to slowing of heart rate during thermodilution cardiac output determination in anesthetized patients.

To identify hemodynamic variables that might indicate susceptibility to slowing of heart rate (HR) and to mean arterial pressure (MAP) decrease caused by cold injectate during thermodilution (TD) cardiac output determination, we measured hemodynamic variables in 32 anesthetized patients undergoing major surgery. A total of 608 cardiac output determinations were evaluated for any relationship between the magnitude of HR decreases and basal hemodynamic variables. The magnitude of HR decrease was pronounced in low cardiac index (CI), low mean pulmonary artery pressure (MPAP), and high systemic vascular resistance index (SVRI). Although there was some decrease in MAP associated with cold injectate, neither changes in SVRI nor those in the other hemodynamic variables correlated with the decreases in MAP. These results suggest that decreased CI and MPAP associated with elevated SVRI may be more susceptible to slowing of HR during cardiac output determination by TD in anesthetized patients.

Adult↗
PubMed1991

Efficacy of dopamine and norepinephrine for treatment of hemodynamic compromise in amitriptyline intoxication.

BACKGROUND AND METHODS: Dopamine and norepinephrine were evaluated for treatment of hemodynamic compromise in amitriptyline intoxication. Fifteen anesthetized dogs underwent hemodynamic monitoring and amitriptyline intoxication, and received three infusion rates of dopamine (5, 15, and 30 micrograms/kg.min) and three infusion rates of norepinephrine (0.25, 0.5, and 1.0 micrograms/kg.min), sequentially, with hemodynamic measurements at each dose. Data were analyzed using repeated-measures analysis of variance; p less than .05 was considered significant. RESULTS: Amitriptyline intoxication lowered cardiac output, peak left ventricular dP/dt, and mean arterial pressure (MAP). All doses of norepinephrine and the two higher doses of dopamine increased cardiac output, MAP, and peak left ventricular dP/dt during the intoxicated state. Both agents restored all variables to preintoxication values. Values obtained at the highest doses of the two drugs were not different for any variable. CONCLUSION: Dopamine and norepinephrine each appeared effective in reversing amitriptyline-induced hemodynamic alterations.

Amitriptyline↗
PubMed1991

Effects of bicarbonate therapy on hemodynamics and tissue oxygenation in patients with lactic acidosis: a prospective, controlled clinical study.

OBJECTIVE: To determine whether correction of acidemia using bicarbonate improves hemodynamic variables and tissue oxygenation in patients with lactic acidosis. DESIGN: Prospective, randomized, blinded, cross over study. Each patient sequentially received sodium bicarbonate and sodium chloride. The order of the infusions was randomized. PATIENTS: Ten patients with metabolic acidosis, increased arterial plasma lactate concentrations (greater than 2.45 mmol/L), and no severe renal failure (creatinine less than 250 mumol/L [less than 2.3 mg/dL]). METHOD: Sodium bicarbonate (1 mmol/kg body weight) or equal volume of sodium chloride was injected iv at the beginning of two successive 1-hr study periods. Period order was randomized. Arterial and venous blood gas measurements, plasma electrolytes (sodium, potassium, chloride), osmolality and lactate, 2,3-diphosphoglycerate (DPG), and oxygen hemoglobin affinity, hemodynamic variables, oxygen delivery, and oxygen consumption measurements were obtained before and repeatedly during the 1-hr period after the injection of bicarbonate or sodium chloride. MEASUREMENTS AND MAIN RESULTS: Sodium bicarbonate administration increased arterial and venous pH, serum bicarbonate, and the partial pressure of CO2 in arterial and venous blood. Hemodynamic responses to sodium bicarbonate and sodium chloride were similar. Tissue oxygenation (as estimated by oxygen delivery, oxygen consumption, oxygen extraction ratio, and transcutaneous oxygen pressure) was not modified. No changes in serum sodium concentration, osmolality, arterial and venous lactate, red cell 2,3-DPG levels, or hemoglobin affinity for oxygen were observed. CONCLUSION: Administration of sodium bicarbonate did not improve hemodynamic variables in patients with lactic acidosis, but did not worsen tissue oxygenation.

Acidosis, Lactic↗
PubMed1993

Hemodynamic and oxygen transport responses in survivors and nonsurvivors of high-risk surgery.

OBJECTIVES: To describe temporal hemodynamic and oxygen transport patterns in a large series of high-risk surgical patients in order to document physiologic patterns, to develop therapeutic goals for a wide range of surgical conditions, and to propose a mechanistic model for acute postoperative circulatory failure. DESIGN: Prospective, longitudinal study. Patients identified as high risk were studied prospectively. The data were analyzed immediately after they were acquired, again on formal rounds twice daily, and at a formal data review after completion of monitoring. SETTING: A university-run county hospital. PATIENTS: The patient series consisted of 708 consecutively monitored high-risk surgical patients. INTERVENTIONS: Hemodynamic and oxygen transport values and their responses to surgical trauma are known to vary widely with age and prior medical conditions; they may be used to predict outcome with a high degree of accuracy. Temporal hemodynamic and oxygen transport patterns in a large series of high-risk surgical operations were treated by one group, using a well-developed protocol. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and oxygen transport monitored variables were analyzed before, during, and at frequent intervals after surgical operations. We stratified the temporal patterns of survivors and nonsurvivors in each of the following groups: a) patients without evidence of cardiovascular disease whose preoperative baseline cardiac index values were normal; and b) patients with high or low preoperative baseline cardiac index values due to the presence of preoperatively identified medical conditions that affect the circulatory status. In addition, we stratified patients in various age ranges who were without known cardiovascular diseases. The present study analyzed over 20,000 data sets with up to 32 variables in each data set or > 500,000 values. The major findings were intraoperatively reduced circulatory functions, principally cardiac index values, oxygen delivery (DO2), and oxygen consumption (VO2). These reductions in circulatory functions intraoperatively were followed, in the early postoperative period, by increases in these variables. The postoperative increases in cardiac index, DO2, and VO2 values were greater in survivors than in nonsurvivors; these findings were more apparent when the postoperative patterns of each strata were related to their own preoperative control values. CONCLUSIONS: The data indicate that there are increased metabolic requirements after surgical trauma and that the changes in cardiac index and DO2 represent compensatory increases in circulatory functions stimulated by increased metabolic needs. However, these metabolic needs change with age, gender, severity of illness, type of operation, associated medical conditions, duration of shock, complications, organ failure, and outcome.

Aged↗
PubMed1994

Beneficial hemodynamic effects of prostaglandin E1 infusion in catecholamine-dependent heart failure: results of a prospective, randomized, controlled study.

OBJECTIVE: To study the hemodynamic effects of prostaglandin E1 (PGE1) administered in addition to a standard catecholamine infusion in patients with severe chronic heart failure. DESIGN: Prospective, placebo-controlled, randomized, single-blind study. SETTING: Intensive care unit at a university hospital. PATIENTS: Thirty patients with severe chronic heart failure, New York Heart Association functional class IV (28 men, two women, with a mean age of 54 +/- 2 yrs, mean left ventricular ejection fraction 10 +/- 0.6%). All patients received oral therapy with digitalis, furosemide (mean dose 300 +/- 46 mg/day), and enalapril (20 +/- 2.7 mg/day). INTERVENTIONS: Hemodynamic measurements using pulmonary artery flotation catheters were performed at baseline, > or = 24 hrs after standardized catecholamine infusion with dopamine (3 micrograms/kg/min) and dobutamine (5 micrograms/kg/min), as well as 48 hrs after randomization to infusion therapy with PGE1 (30 ng/kg/min) or a placebo. MEASUREMENTS AND MAIN RESULTS: The addition of PGE1 to an ongoing catecholamine infusion in 20 patients caused a 16 +/- 4% decrease in mean pulmonary arterial pressure (p < .001), a 22 +/- 5% decrease in pulmonary artery occlusion pressure (p < .0001), a 24 +/- 8% decrease in pulmonary vascular resistance index (p < .001), a 20 +/- 9% decrease in right atrial pressure (p < .01), a 14 +/- 3% decrease in mean arterial pressure (p < .001), and a 29 +/- 4% decrease in systemic vascular resistance index (p < .0001). These PGE1-induced decreases occurred without a change in heart rate. Stroke volume index increased with PGE1 therapy by 34 +/- 7% (p < .0001), and cardiac index increased by 34 +/- 6% (p < .0001). No hemodynamic changes were observed during combined infusion with catecholamines and placebo in ten patients. CONCLUSION: PGE1 improves the hemodynamic state in end-stage chronic heart failure patients already receiving a standard dose dopamine/dobutamine infusion.

Alprostadil↗
PubMed1995

Early hemodynamic course of septic shock.

OBJECTIVE: To assess the relative contributions of changes in vascular tone and changes in cardiac function to hemodynamic recovery from septic shock. DESIGN: Case series, observational study. SETTING: Multidisciplinary department of intensive care in an academic hospital. PATIENTS: Sixty-seven patients with septic shock (prolonged hypotension, signs of tissue hypoperfusion, signs of sepsis, suspected source of infection, or documented bacteremia). In addition to the antibiotic therapy and the removal of the source of sepsis whenever possible, each patient received intravenous fluids and vasoactive agents (dopamine, norepinephrine, and dobutamine). Each patient was also treated with mechanical ventilation. Twenty-four (36%) patients survived their intensive care unit course. INTERVENTIONS: Hemodynamic measurements were obtained at baseline, after initial resuscitation (as soon as apparent hemodynamic stability was achieved), after 12 hrs, and after 24 hrs. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in hemodynamic or oxygen-derived variables at baseline between the survivors and the nonsurvivors. During the initial resuscitation period, only the survivors demonstrated a significant increase in mean arterial pressure (from 69 +/- 17 to 82 +/- 18 mm Hg; p < .02) and left ventricular stroke work index (from 25.2 +/- 11.0 to 35.5 +/- 19.4 g.m/m2; p < .05). The increases in cardiac index and systemic vascular resistance were greater in the survivors than in the non-survivors, but the differences did not reach statistical significance. Study of the left ventricular function curves indicated an improvement of left ventricular function in the survivors but not in the nonsurvivors. CONCLUSION: An early improvement in left ventricular function is a hallmark of the survivors from septic shock.

Adolescent↗
PubMed1996

Effects of pentoxifylline on circulating cytokine concentrations and hemodynamics in patients with septic shock: results from a double-blind, randomized, placebo-controlled study.

OBJECTIVE: To determine whether a continuous intravenous infusion of pentoxifylline, a methylxanthine derivative, alters the serum cytokine concentrations and/or hemodynamic measurements in patients with septic shock. DESIGN: A prospective, randomized, double-blind, placebo-controlled study. SETTING: Medical intensive care unit in a university hospital. PATIENTS: Sixteen patients with septic shock. INTERVENTIONS: Patients were randomly assigned to receive either pentoxifylline (1 mg/kg) followed by an infusion of 1.5 mg/kg/hr for 24 hrs (n = 8), or placebo (n = 8). MEASUREMENTS AND MAIN RESULTS: Tumor necrosis factor (TNF) and interleukin (IL)-6 concentrations were measured by radioimmunoassays; IL-8 concentrations by an enzyme-linked immunosorbent assay (ELISA) and pentoxifylline concentrations by high-performance liquid chromatography at 0, 3, 6, 12, 18, 24 and 48 hrs after study entry. Pulmonary artery catheter-derived hemodynamics were measured at 0, 0.75, 3, 6, 12, 18, and 24 hrs. In pentoxifylline-treated patients, at 24 hrs, serum concentrations of TNF were significantly lower compared with controls (12 +/- 2 vs. 42 +/- 12 pg/mL, respectively, p = .04). Serum concentrations of IL-6 and IL-8 did not differ between the two treatment groups. There were also no significant differences in any hemodynamic and oxygenation measurements comparing the two treatment groups. Pentoxifylline concentrations were 1,544 +/- 241 ng/mL after the initial dose, and 5,776 +/- 1,781 ng/mL at the end of the 24-hr infusion. Five patients in the pentoxifylline group and four patients in the placebo group died. CONCLUSIONS: Pentoxifylline is able to decrease serum TNF but not IL-6 or IL-8 serum concentrations during septic shock. Pentoxifylline was well tolerated by all eight patients with no adverse effect. Further studies are needed to determine if pentoxifylline's ability to lower circulating TNF concentration without altering hemodynamics will improve outcome in septic shock.

Adult↗