Effects of levosimendan on systemic and regional hemodynamics in septic myocardial depression.
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Belgium↗
Biomedical subjects
Jacques Creteur
Publications and source records attributed to Jacques Creteur.
Sublingual capnometry tracks microcirculatory changes in septic patients.
OBJECTIVE: To test the hypothesis that microcirculatory blood flow is the main determinant of sublingual carbon dioxide pressure in patients with septic shock. DESIGN: Prospective, open-label study. SETTING: A 31-bed medico-surgical department of intensive care. PATIENTS: Eighteen consecutive mechanically ventilated patients with septic shock. INTERVENTIONS: A 5 microg/kg x min dobutamine infusion was used to increase blood flow. METHODS: Sublingual carbon dioxide pressure was monitored using a microelectrode sensor, and sublingual microcirculation was assessed using orthogonal polarization spectral imaging. The sublingual carbon dioxide pressure gap was calculated as the difference between sublingual and arterial carbon dioxide pressures. In each patient, a nasogastric tonometry catheter was inserted for gastric mucosal carbon dioxide pressure measurement. The gastric carbon dioxide pressure gap was calculated as the difference between gastric mucosal and arterial carbon dioxide pressures. MEASUREMENTS AND RESULTS: Dobutamine infusion was associated with increases cardiac index and mixed venous blood oxygen saturation. Dobutamine infusion resulted in decreases in sublingual carbon dioxide pressure gap from 40+/-15 to 17+/-8 mmHg (p<0.01). There was a significant correlation between sublingual and gastric mucosal carbon dioxide pressures (r 2=0.61, p<0.05). At baseline, sublingual carbon dioxide pressure gap correlated with the proportion of well-perfused capillaries (r 2=0.80). The decrease in sublingual carbon dioxide pressure gap paralleled the increase in the proportion of well-perfused capillaries in each patient. CONCLUSIONS: Regional microcirculatory blood flow is the main determinant of sublingual carbon dioxide pressure. Sublingual capnometry could represent a simple, non-invasive method to monitor these microcirculatory alterations in septic patients.
Aged↗
The effects of dobutamine on microcirculatory alterations in patients with septic shock are independent of its systemic effects.
OBJECTIVE: To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock. DESIGN: Prospective, open-label study. SETTING: A 31-bed, medico-surgical intensive care unit of a university hospital. PATIENTS: Twenty-two patients with septic shock. INTERVENTIONS: Intravenous administration of dobutamine (5 mug/kg.min) for 2 hrs (n = 22) followed by the addition of 10 M acetylcholine (topically applied, n = 10). MEASUREMENTS AND MAIN RESULTS: Complete hemodynamic measurements were obtained before and after dobutamine administration. In addition, the sublingual microcirculation was investigated with an orthogonal polarization spectral imaging technique before and after dobutamine administration and after topical application of acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 +/- 15 to 67 +/- 11%, p = .001), but with large individual variation, whereas capillary density remained stable. The addition of topical acetylcholine completely restored capillary perfusion (98 +/- 1%, p = .001) and capillary density. The changes in capillary perfusion during dobutamine administration were not related to changes in cardiac index (p = .45) or arterial pressure (p = .29). Interestingly, the decrease in lactate levels was proportional to the improvement in capillary perfusion (y = 0.07 - 0.02x, r = .46, p = .005) but not to changes in cardiac index (p = .55). CONCLUSIONS: The administration of 5 mug/kg.min dobutamine can improve but not restore capillary perfusion in patients with septic shock. These changes are independent of changes in systemic hemodynamic variables.
Acetylcholine↗
Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: results of a randomized, double-blind, placebo-controlled trial.
OBJECTIVE: To describe the erythropoietin pharmacokinetic profile after once-weekly epoetin alfa treatment in critically ill patients. Secondary objectives were to compare pharmacodynamic and safety profiles between active treatment and placebo in these patients. DESIGN: Randomized, double-blind, placebo-controlled study. SETTING: Medical, surgical, or mixed medical/surgical intensive care units. PATIENTS: A total of 73 anemic critically ill adults with an expected stay of >3 days and a hematocrit value of <38%. INTERVENTIONS: Patients were randomized 2:1 to epoetin alfa, 40,000 IU, administered subcutaneously once weekly (n=48) or matching placebo (n=25) for up to 4 wks. MEASUREMENTS AND MAIN RESULTS: Serum erythropoietin concentration and hematologic variables (percentage reticulocytes [RETI], hemoglobin [Hb], and total red blood cell [RBC] counts) were measured, and area under the serum concentration-time curve from time 0 to the last blood sampling time at time t (t: 120, 144, or 168 hrs) postdose (AUC0-Tlast) for these three variables was determined. Mean serum erythropoietin concentrations in placebo patients were slightly higher than typical physiologic levels of erythropoietin in healthy subjects, although not appropriate for the degree of anemia in these patients. Overall, exposure of endogenous erythropoietin in the placebo group (in terms of AUC0-Tlast) was only about 20% of exposure to exogenous erythropoietin in the epoetin alfa group. Baseline hemoglobin levels were the same in both groups (9.9 g/dL). Mean change in hemoglobin level from baseline through day 29 was 1.9 g/dL and 1.6 g/dL in the epoetin alfa and placebo groups, respectively. Mean AUC(RETI)0-Tlast was higher with epoetin alfa than with placebo and was related to the AUC of erythropoietin. There were no apparent differences in AUC(Hb)0-Tlast and AUC(RBC)0-Tlast between epoetin alfa and placebo groups, which was most likely due to bleeding and transfusion events. Epoetin alfa was safe and well tolerated, with a rate of treatment-emergent complications similar to that seen with placebo. CONCLUSION: Epoetin alfa, once weekly, augmented the erythropoietic response in critically ill patients as indicated by the increased erythropoietin levels and larger AUC(RETI)0-Tlast in treated patients.
Adolescent↗
Gastric and sublingual capnometry.
PURPOSE OF REVIEW: Tissue hypoperfusion is a common pathophysiologic process leading to multiple organ dysfunction and death. Increases in tissue PCO2 can reflect an abnormal oxygen supply to the cells, so that monitoring tissue PCO2 by the use of gastric or sublingual capnometry may help identify circulatory abnormalities and guide their correction. This review provides an update on these technologies. RECENT FINDINGS: Gastric tonometry aims at monitoring PCO2 in the stomach, an organ that becomes ischemic quite early when the circulatory status is jeopardized. Despite substantial initial enthusiasm, this technique has never been widely implemented due to methodological problems. The measurement of sublingual mucosal PCO2 (PslCO2) by sublingual capnometry is technically simple and noninvasive. Experimental studies have suggested that PslCO2 is a reliable marker of tissue perfusion. Clinical studies have demonstrated that high PslCO2 values are associated with impaired microcirculatory blood flow and a worse prognosis in critically ill patients. SUMMARY: Gastric tonometry was proposed for regional PCO2 monitoring, but it is prone to a number of technical limitations. Sublingual capnometry could offer a valuable alternative for tissue PCO2 monitoring in clinical practice, representing a simple, noninvasive method to monitor tissue perfusion and titrate therapeutic interventions in critically ill patients.
Capnography↗
Lactate concentration gradient from right atrium to pulmonary artery: a commentary.
Inadequate myocardial performance is a common complication of severe sepsis. Studies in humans strongly argue against a decrease in coronary blood flow in the pathogenesis of this sepsis-induced cardiac injury. Moreover, regional myocardial ischemia may well be present in sepsis patients with coexistent coronary artery disease. Nevertheless, the diagnosis of myocardial ischemia remains difficult in patients with sepsis, since elevation of troponin in these patients can be the result of a variety of conditions other than acute myocardial ischemia. The use of the right atrium to pulmonary artery lactate gradient could perhaps help the clinician in detecting myocardial ischemia in patients with sepsis.
Biomarkers↗
The following is the abstract of the article discussed in the subsequent letter:.
Sublingual and intestinal mucosal blood flow and Pco(2) were studied in a canine model of endotoxin-induced circulatory shock and resuscitation. Sublingual Pco(2) (Ps(CO(2))) was measured by using a novel fluorescent optrode-based technique and compared with lingual measurements obtained by using a Stowe-Severinghaus electrode [lingual Pco(2) (Pl(CO(2)))]. Endotoxin caused parallel changes in cardiac output, and in portal, intestinal mucosal, and sublingual blood flow (Q(s)). Different blood flow patterns were observed during resuscitation: intestinal mucosal blood flow returned to near baseline levels postfluid resuscitation and decreased by 21% after vasopressor resuscitation, whereas Q(s) rose to twice that of the preshock level and was maintained throughout the resuscitation period. Electrochemical and fluorescent Pco(2) measurements showed similar changes throughout the experiments. The shock-induced increases in Ps(CO(2)) and Pl(CO(2)) were nearly reversed after fluid resuscitation, despite persistent systemic arterial hypotension. Vasopressor administration induced a rebound of Ps(CO(2)) and Pl(CO(2)) to shock levels, despite higher cardiac output and Q(s), possibly due to blood flow redistribution and shunting. Changes in Pl(CO(2)) and Ps(CO(2)) paralleled gastric and intestinal Pco(2) changes during shock but not during resuscitation. We found that the lingual, splanchnic, and systemic circulations follow a similar pattern of blood flow variations in response to endotoxin shock, although discrepancies were observed during resuscitation. Restoration of systemic, splanchnic, and lingual perfusion can be accompanied by persistent tissue hypercarbia, mainly lingual and intestinal, more so when a vasopressor agent is used to normalize systemic hemodynamic variables.
Animals↗
Tissue capnometry: does the answer lie under the tongue?
Increases in tissue partial pressure of carbon dioxide (PCO(2)) can reflect an abnormal oxygen supply to the cells, so that monitoring tissue PCO(2) may help identify circulatory abnormalities and guide their correction. Gastric tonometry aims at monitoring regional PCO(2) in the stomach, an easily accessible organ that becomes ischemic quite early when the circulatory status is jeopardized. Despite substantial initial enthusiasm, this technique has never been widely implemented due to various technical problems and artifacts during measurement. Experimental studies have suggested that sublingual PCO(2 )(P(sl)CO(2)) is a reliable marker of tissue perfusion. Clinical studies have demonstrated that high P(sl)CO(2) values and, especially, high gradients between P(sl)CO(2) and arterial PCO(2) (DeltaP(sl-a)CO(2)) are associated with impaired microcirculatory blood flow and a worse prognosis in critically ill patients. Although some questions remain to be answered about sublingual capnometry and its utility, this technique could offer new hope for tissue PCO(2) monitoring in clinical practice.
Animals↗
Effects of fluid challenge on gastric mucosal PCO2 in septic patients.
OBJECTIVE: To determine the effects of fluid challenge on systemic hemodynamic variables and gastric intramucosal partial pressure of carbon dioxide (PCO(2)) in septic patients. DESIGN: Short-term interventional study. SETTING: Medical-surgical intensive care unit in a university hospital. PATIENTS: Twenty-four adult patients with severe sepsis or septic shock requiring volume replacement. All patients were studied within 24 h of onset of severe sepsis or septic shock. INTERVENTIONS: Five hundred milliliters of a 6% hydroxyethyl starch (HES) solution were administered in 30 min. MEASUREMENTS AND RESULTS: Complete hemodynamic data, blood samples, and gastric mucosal PCO(2) (automatic gas capnometry) determinations were obtained at baseline and 15 min after the end of fluid infusion. After fluid challenge, cardiac index (CI) increased from 3.8 (range 2.9-4.2) to 4.2 (range 3.1-4.9) l/min m(-2) ( p<0.05). The PCO(2) gap decreased from 9.8 (range 6.9-26.0) to 8.5 (range 6.6-17.4) mm Hg ( p<0.05), but important individual variations were observed. We failed to observe significant relationships between changes in CI and in PCO(2) gap, or between indices of preload (pulmonary artery occluded pressure, right atrial pressure, and pulse pressure variations) and changes in PCO(2) gap. In addition, changes in PCO(2) gap and in (v-a) CO(2) were not related; however, changes in PCO(2) gap were related to baseline PCO(2) gap ( p=0.003), PEEP ( p=0.02), and cumulative doses of vasopressors ( p=0.02). CONCLUSIONS: The effects of fluid challenge on gastric mucosal PCO(2) are variable and related to baseline PCO(2) gap rather than to systemic variables. In general, rapid volume infusion decreases PCO(2) gap, but this effect is more pronounced in patients with presumably impaired mucosal perfusion.
Adult↗
Microvascular alterations in patients with acute severe heart failure and cardiogenic shock.
BACKGROUND: Microvascular blood flow alterations may impair tissue oxygenation and may participate in the development of multiple organ failure in patients with severe heart failure. We hypothesized that microvascular blood flow alterations are present in patients with severe heart failure and cardiogenic shock. METHODS: We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 40 patients with acute severe heart failure, including 31 patients with cardiogenic shock, and in a control group of 15 patients who were examined the day before cardiac surgery. The effects of topical application of acetylcholine (10-2M) were also tested in 5 patients with cardiogenic shock. Five sublingual areas were recorded, allocated a random number, and later analyzed semiquantitatively. Data were analyzed with non-parametric tests and presented as medians (percentiles 25-75). RESULTS: The density of all the vessels was similar in the 3 groups. The proportion of perfused small (<20 microm) vessels was lower in patients with cardiac failure and cardiogenic shock than in control patients (63% [46%-65%] and 49% [38%-64%] vs 92% [90%-93%], P <.001). The perfusion of large vessels was preserved in all groups. The proportion of perfused vessels was higher in patients who survived than in patients who did not survive in all vessels (90% [84%-93%] vs 81% [74%-87%], P <.05) and in small vessels (64% [49%-68%] vs 43% [37%-62%], P <.05). The topical application of acetylcholine totally reversed these alterations CONCLUSIONS: Microvascular blood flow alterations are frequently observed in patients with severe heart failure and are more severe in patients who do not survive.
Acetylcholine↗
The hepatosplanchnic contribution to hyperlactatemia in endotoxic shock: effects of tissue ischemia.
We investigated the role of the hepatosplanchnic region in the hyperlactatemia observed during endotoxic shock. The study included 18 dogs anesthetized with pentobarbital and mechanically ventilated. After baseline measurements, including gut lactate production (GLP), liver lactate uptake (LLU), liver lactate extraction (LLE), and hepatosplanchnic lactate production (HSLP), each dog received 2 mg/kg of E. coli endotoxin. After a second set of measurements, cardiac tamponade was induced in 12 dogs (EDTX + Tamp) by repeated injections of normal saline into the pericardial sac to progressively reduce cardiac output and hepatic blood flow. The six remaining dogs served as septic controls (EDTX). From a net lactate consumer before endotoxin infusion, the gut became a lactate producer after the endotoxin infusion, with GLP increasing from -11.4 +/- 27.0 to 32.9 +/- 38.2 x 10(-3) mEq/min (P < 0.05). LLU increased from 48.1 +/- 26.2 to 86.6 +/- 45.2 x 10(-3) mEq/min (P < 0.05), so that LLE and HSLP did not change. In the EDTX + Tamp group, LLE became negative, and HSLP became positive only when hepatic oxygen delivery reached its critical value during cardiac tamponade. In the EDTX group, LLE remained positive and HSLP negative. In endotoxic shock, GLP is increased, but the liver can metabolize this additional load of lactate, so that the hepatosplanchnic area is not a major source of lactate unless the liver becomes profoundly hypoxic.
Animals↗
Persistent microcirculatory alterations are associated with organ failure and death in patients with septic shock.
OBJECTIVE: To characterize the time course of microcirculatory alterations and their relation to outcome in patients with septic shock. DESIGN: Prospective, observational study. SETTING: Thirty-one-bed, medico-surgical intensive care unit in a university hospital. PATIENTS: Forty-nine patients with septic shock. INTERVENTIONS: The sublingual microcirculation was investigated with an orthogonal polarization spectral imaging device on the day of onset of septic shock (baseline) and each day until resolution of shock. MEASUREMENTS AND MAIN RESULTS: Five sequences of 20 secs each were recorded and analyzed off-line by a semiquantitative method. Data were analyzed with nonparametric tests and presented as median (25th-75th percentiles). Three patients died after the resolution of shock from unrelated causes and were excluded. Of the other 46 patients, 26 survived and 20 died: 13 due to unresolving shock and seven due to persistent multiple organ failure after resolution of shock. At the onset of shock, survivors and nonsurvivors had similar vascular density (5.6 [4.7-7.0] vs. 6.2 [5.4-7.0]/mL; p = nonsignificant) and percentage of perfused small vessels (65.0 [53.1-68.9] vs. 58.4 [47.5-69.1]%; p = nonsignificant). Small vessel perfusion improved over time in survivors (analysis of variance, p <.05 between survivors and nonsurvivors) but not in nonsurvivors. Despite similar hemodynamic and oxygenation profiles and use of vasopressors at the end of shock, patients dying after the resolution of shock in multiple organ failure had a lower percentage of perfused small vessels than survivors (57.4 [46.6-64.9] vs. 79.3 [67.2-83.2]%; p =.02). CONCLUSIONS: Microcirculatory alterations improve rapidly in septic shock survivors but not in patients dying with multiple organ failure, regardless of whether shock has resolved.
Aged↗
Use of low tidal volume in septic shock may decrease severity of subsequent acute lung injury.
Recent studies have indicated that protective lung strategies may improve outcomes in acute lung injury. We hypothesized that the use of a lower tidal volume early during septic shock may protect against the subsequent development of acute lung injury. Fourteen fasted, anesthetized, invasively monitored, mechanically ventilated, female sheep (26.4 +/- 4.5 kg) underwent cecal ligation and perforation to induce sepsis. Sheep were then randomized to ventilation with low (6 mL/kg) or high (12 mL/kg) tidal volumes. A positive end-expiratory pressure of 10 cm H(2)O was applied in each case. Ringer's lactate was titrated to maintain pulmonary artery occlusion pressure at baseline levels. No vasoactive agents or antibiotics were used. Survival time was longer in the low- than in the high-tidal-volume group (21.8 +/- 2.4 vs. 17.6 +/- 4.1 h, respectively, P < 0.05). The times to develop hypotension and anuria were longer in the low-tidal-volume group (18.1 +/- 3.1 vs. 12.0 +/- 2.8 h, P < 0.05, and 17.6 +/- 1.6 vs. 14.1 +/- 3.8 h, P < 0.05). Although the Pao2/Fio2 tended to be lower in the low- than in the high-tidal-volume group (P = 0.06), postmortem examination showed a lower lung tissue wet/dry ratio in the low- than in the high-tidal-volume group (7.1 +/- 0.5 vs. 9.1 +/- 0.7, P < 0.05). A low-tidal-volume ventilation strategy applied early during septic shock may be beneficial in terms of reducing the amount of lung edema and prolonging survival time.
Animals↗
Arginine vasopressin in advanced vasodilatory shock.
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Arginine Vasopressin↗
Effect of vasopressin on sublingual microcirculation in a patient with distributive shock.
OBJECTIVE: To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass. DESIGN AND SETTING: Case-report in the Department of Intensive Care of a university hospital. PATIENT: A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents. METHODS: Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered. CONCLUSIONS: Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.
Blood Pressure↗
Perioperative optimization and right heart catheterization: what technique in which patient?
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Catheterization, Swan-Ganz↗
The 32nd Annual Congress of the Society of Critical Care Medicine, 28 January - 2 February 2003, San Antonio, USA.
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Critical Care↗
Regional hypoxia and partial pressure of carbon dioxide gradients: what is the link?
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Animals↗