Martine Arthaud

Inhaled nitric oxide in acute respiratory failure : dose-response curves

ObjectiveTo determine the dose-response curve of inhaled nitric oxide (NO) in terms of pulmonary vasodilation and improvement in PaO2 in adults with severe acute respiratory failure.DesignProspective randomized study.SettingA 14-bed ICU in a teaching hospital.Patients6 critically ill patients with severe acute respiratory failure (lung injury severity score ≥2.5) and pulmonary hypertension.Interventions8 concentrations of inhaled NO were administered at random: 100, 400, 700, 1000, 1300, 1600, 1900 and 5000 parts per billion (ppb). Control measurements were performed before NO inhalation and after the last concentration administered. After an NO exposure of 15–20 min, hemodynamic parameters obtained from a fiberoptic Swan-Ganz catheter, blood gases, methemoglobin blood concentrations and intratracheal NO and nitrogen dioxide (NO2) concentrations, continuously monitored using a bedside chemiluminescence apparatus, were recorded on a Gould ES 1000 recorder. In 2 patients end-tidal CO2 was also recorded.ResultsThe administration of 100–2000 ppb of inhaled NO induced: i) a dose-dependent decrease in pulmonary artery pressure and in pulmonary vascular resistance (maximum decrease −25%); ii) a dose-dependent increase in PaO2 via a dose-dependent reduction in pulmonary shunt; iii) a slight but significant decrease in PaCO2 via a reduction in alveolar dead space; iv) a dose-dependent increase in mixed venous oxygen saturation (SVO2). Systemic hemodynamic variables and methemoglobin blood concentrations did not change. Maximum NO2 concentrations never exceeded 165 ppb. In 2 patients, 91% and 74% of the pulmonary vasodilation was obtained for inhaled NO concentrations of 100 ppb.ConclusionIn hypoxemic patients with pulmonary hypertension and severe acute respiratory failure, therapeutic inhaled NO concentrations are in the range 100–2000 ppb. The risk of toxicity related to NO inhalation is therefore markedly reduced. Continuous SVO2 monitoring appears useful at the bedside for determining optimum therapeutic inhaled NO concentrations in a given patient.

Inhaled Nitric Oxide Reverses the Increase in Pulmonary Vascular Resistance Induced by Permissive Hypercapnia in Patients with Acute Respiratory Distress Syndrome

BackgroundThe aim of this prospective study was to determine if inhaled nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permissive hypercapnia in patients with acute respiratory distress syndrome. MethodsIn 11 critically ill patients (mean age 59 ± 22 yr) with acute respiratory distress syndrome (Murray Score 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied: normocapnla (arterial carbon dioxide tension 38 ± 6 mmHg, tidal volume 655 ± 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia (arterial carbon dioxide tension 65 ± 15 mmHg, tidal volume 330 ± 93 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings were made of heart rate, arterial pressure, pulmonary artery pressure, tracheal pressure, and tidal volume (by pneumotachograph). At the end of each condition, arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac output were measured. Simultaneous arterial and mixed venous blood samples were obtained to measure arterial oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglobin oxygen saturation, pH, and blood hemoglobin and methemoglobin concentrations (by hemoximeter). In addition, plasma concentrations of catecholamines were measured with a radioenzymatic assay. In 5 patients, end-tidal carbon dioxide tension was measured with a nonaspirative infrared capnometer. Calculations were made of pulmonary vascular resistance index, systemic vascular resistance index, true pulmonary shunt, and alveolar dead space. ResultsDuring hypercapnia, NO decreased pulmonary vascular resistance Index from 525 ± 223 to 393 ± 142 dyn. s. cm−5. m−2 (P < 0.01), a value similar to that measured in normocapnic conditions (391 ± 122 dyn. s. cm−5. m−2). It also reduced mean pulmonary artery pressure from 40 ± 9 to 35 ± 8 mmHg (P < 0.01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 ± 67 to 270 ± 87 mmHg during normocapnia and from 189 ± 73 to 258 ± 101 mmHg during hypercapnia (P < 0.01). NO decreased true pulmonary shunt during normocapnia (from 34 ± 3% to 28 ± 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 ± 7% vs. 38 ± 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 ± 7% to 28 ± 10% in normocapnic conditions and from 30 ± 9% to 22 ± 10% in hypercapnic conditions (P < 0.05). ConclusionsInhaled NO completely reversed the increase in pulmonary vascular resistance Index induced by acute permissive hypercapnia. It only partially reduced the pulmonary hypertension induced by acute permissive hypercapnia, probably because the flow component of the Increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxygenation after NO administration was observed during normocapnic and hypercapnic conditions. A ventilation strategy combining permissive hypercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonary circulation.

Acute left ventricular dilatation and shock-induced myocardial dysfunction*

Objective:Whether cardiac ventricles can acutely dilate during septic myocardial dysfunction. Design:A prospective echocardiographic study was performed to assess changes of left ventricular dimensions over time in patients with septic shock. Settings:A 20-bed surgical intensive care unit of Pitié-Salpêtrière university hospital in Paris. Patients:Forty-five patients were studied over the first 10 days of septic shock. Interventions:None. Measurements and Main Results:Left ventricular end-diastolic area (LVEDA), fractional area change (FAC), velocity time integral of the aortic flow, echocardiographic indices of left ventricular relaxation, and cardiac troponin I (cTnI) were measured at day 1, 2, 3, 4, 7, and 10. Three groups were defined: 29 patients without increased cTnI and cardiac impairment (group 1), eight patients with increased cTnI and left systolic ventricular dysfunction (group 2), and eight patients with increased cTnI and isolated impairment of left ventricular relaxation (group 3). At day 1, LVEDA was significantly higher in group 2 (13 ± 3 cm/m2, p < 0.05) compared with groups 1 (10 ± 2 cm/m2) and 3 (11 ± 2 cm/m2). LVEDA did not change in groups 1 and 3. In group 2, LVEDA and FAC returned within 10 days to values observed in groups 1 and 2. A significant correlation was found between aortic velocity time integral and LVDEA (r =.78, p = 0.022) and FAC (r =.89, p = 0.003) only in group 2. Conclusions:Acute and reversible left ventricular dilation accompanies septic shock-induced systolic left ventricular dysfunction. When septic myocardial abnormalities are limited to reversible impairment of left ventricular relaxation, left ventricular dimensions remain unchanged.

Isolated and reversible impairment of ventricular relaxation in patients with septic shock.

Objective:Many patients with septic shock and increased cardiac troponin I (cTnI) do not exhibit significant left ventricular systolic dysfunction. We hypothesized that an isolated and reversible impairment of ventricular relaxation may be associated with the increase in cTnI. Design:Prospective, observational study. Setting:Surgical intensive care unit in a university hospital. Patients:Total of 54 patients with septic shock. Interventions:Fractional area change, early diastolic velocity of mitral annulus, flow propagation velocity of early diastolic mitral inflow, cTnI, tumor necrosis factor-&agr;, interleukin (IL)-6, -1&bgr;, -8, and -10 were measured at days 1, 2, 3, 4, 7, and 10 after onset of septic shock. Patients were classified into three groups: normal cTnI (group 1), increased cTnI and fractional area change <50% (group 2), and increased cTnI and fractional area change >50% (group 3). Measurements and Main Results:A total of 22 patients had an increase in cTnI, 11 with both systolic and diastolic dysfunctions and 11 with isolated impairment of left ventricular relaxation. At day 1, early diastolic velocity of mitral annulus and flow propagation velocity of early diastolic mitral inflow were significantly lower and tumor necrosis factor-&agr;, IL-8, and IL-10 significantly higher in groups 2 and 3 compared with group 1. With resolution of septic shock, early diastolic velocity of mitral annulus and flow propagation velocity of early diastolic mitral inflow measured in patients of groups 2 and 3 returned progressively to values observed in group 1, with a parallel normalization of tumor necrosis factor-&agr;, IL-8, and IL-10. Conclusions:Isolated and reversible impairment of left ventricular relaxation, associated with transient increases in cTnI, tumor necrosis factor-&agr;, IL-8, and IL-10, was observed in 20% of patients with septic shock.

Circulating Cardiac Troponin T in Potential Heart Transplant Donors

BACKGROUND Brain death may induce myocardial dysfunction, the mechanisms of which are not yet fully understood. Circulating cardiac troponin T is considered a highly sensitive and specific marker of myocardial cell injury. METHODS AND RESULTS We prospectively measured circulating cardiac troponin T in 100 brain-dead patients and measured the left ventricular ejection fraction area (LVEFa), using transesophageal echocardiography. Sixty-one patients had normal LVEFa, 25 had moderate decrease in LVEFa (30% to 50%), and 14 had severe decrease in LVEFa (< or = 30%). Circulating cardiac troponin T concentrations were significantly higher (1.68 +/- 1.03 micrograms/L-1, P < .01) in patients with a severe decrease in LVEFa than in the two other groups (0.42 +/- 0.43 and 0.12 +/- 0.16 microgram/L-1, respectively), and there was a significant correlation between LVEFa and cardiac troponin T concentration (p = -0.59, P < .0001). An elevated circulating cardiac troponin T concentration (> or = 0.5 microgram/L-1) was more accurate (sensitivity, 1.00; specificity, 0.84) in predicting a severe decrease in LVEFa than an elevated CKMB value or an increased CKMB/CK ratio. CONCLUSIONS An elevated circulating cardiac troponin T was associated with a severe decrease in LVEFa in brain-dead patients, suggesting that severe and potentially irreversible myocardial cell damage occurred. In contrast, CKMB determination was not useful. Since the quality of the donors heart is considered an important prognosis factor in heart transplantation, the determination of circulating cardiac troponin T concentration could be useful to the heart transplantation team.

Effects of Propofol and Thiopental on Coronary Blood Flow and Myocardial Performance in an Isolated Rabbit Heart

BackgroundSome clinical and experimental studies suggest that propofol decreases myocardial contractility and relaxation, whereas others report preserved cardiac function. To investigate the effects of propofol on intrinsic contractility and relaxation, increasing concentrations of propofol were infused in isolated blood-perfused rabbit hearts. Equimolar concentrations of thiopental were infused as a reference group. MethodsCoronary blood flow, left ventricular contractility and relaxation (as maximal positive and negative left ventricular pressure derivatives [dP/dtmax and dP/dtmin], respectively), and myocardial oxygen consumption (MvO2) were measured during infusion of 10–1,000 μM propofol in bloodperfused hearts. To determine whether the effects of propofol depend on the hearts perfusate, propofol also was infused in isolated buffer-perfused rabbit hearts. In addition, the effects of propofol solvent were investigated in blood- and buffer-perfused preparations. ResultsIn blood-perfused preparations, coronary blood flow increased with propofol concentrations greater than 30 μM and with 300 and 1,000 μM thiopental. Left ventricular dP/dtmax and dP/dtmin remained unchanged with propofol and decreased with concentrations of thiopental equal to or greater than 30 μM. MvO2 increased with 1,000 μM propofol, whereas coronary venous oxygen tension and content remained unchanged. MvO2 decreased with thiopental associated with a significant increase in coronary venous oxygen tension and content. In six buffer-perfused hearts, basal coronary blood flow was much greater and MvO2 less than in blood-perfused hearts. Left ventricular dP/dtmax and dP/dtmin decreased with 30, 100, and 300 μM propofol. Propofol vehicle did not change coronary blood flow, myocardial performance, or MvO2 of blood- or buffer-perfused hearts. ConclusionsWhen compared to a reference drug such as thiopental, propofol did not depress the myocardial performance of blood-perfused rabbit hearts. The type of the perfusate (blood vs. buffer), however, had a major influence on the myocardial effects of propofol.

Mechanisms of increased myocardial contractility with hypertonic saline solutions in isolated blood-perfused rabbit hearts

Hypertonic saline improves organ perfusion and animal survival during hemorrhagic shock because it expands plasma volume and increases tissue oxygenation.Because both decreased and increased myocardial performance have been reported with hypertonic saline, the effects of hyperosmolarity and the mechanism accounting for it were investigated in isolated blood-perfused rabbit hearts. Coronary blood flow (CBF), myocardial contractility, relaxation, and oxygen consumption were measured during administration of blood perfusates containing 140-180 mmol sodium concentrations ([Na+]). In two other series of experiments, the role of Na+-Ca2+ exchange in the inotropic effect of hyperosmolarity (160 mmol sodium concentration) and hypertonicity (sucrose) were also investigated. Hypertonic [Na+] induced a significant increase in contractility and relaxation, combined with a coronary vasodilation. Myocardial oxygen consumption (MvO2) increased at all hypertonic [Na+] without significant change in coronary venous oxygen tension (PvO2) and content (CvO2). Amiloride (0.3 mmol) inhibited the improved contractility observed with 160 mmol sodium. Similar Na+-Ca2+ exchanger blockade did not inhibit the inotropic effect of sucrose. These results confirm the positive inotropic effect of hypertonic [Na+]. The inhibition of this improvement by amiloride suggests that calcium influx through the sarcolemna could be the major mechanism of this effect. (Anesth Analg 1995;81:777-82)

Comparison of troponin I and N-terminal-pro B-type natriuretic peptide for risk stratification in patients with pulmonary embolism.

Objective We compared the usefulness of plasma N-terminal-pro B-type natriuretic peptide and troponin I levels for risk stratification of patients with pulmonary embolism. Methods This was a prospective study performed in an emergency department. N-terminal-B-type natriuretic peptide assay and troponin I were performed blindly at admission in patients with pulmonary embolism confirmed by imaging tests. A complicated pulmonary embolism was defined as any of the following: death, cardiopulmonary resuscitation, requirement for mechanical ventilation, use of pressors, thrombolysis, surgical embolectomy or admission in an intensive care unit. Results Sixty patients (mean age±standard deviation of 72±15 years) were included. Seventeen (28%) patients had adverse events: all were admitted in intensive care unit, one was treated with surgical embolectomy and one with thrombolysis, and three died. The median N-terminal-pro B-type natriuretic peptide level (95% confidence interval) was higher in the group of patients with complicated pulmonary embolism, 4086 pg/ml (505–8998) versus 352 pg/ml (179–662), respectively (P<0.05). The mean value of troponin I was similar in the complicated pulmonary embolism group, 0.09±0.17 μg/l versus 0.08±0.41 μg/l, respectively (P=0.93). The best threshold value of N-terminal-pro B-type natriuretic peptide was 1000 pg/ml, and the receiver operating characteristic curve demonstrated that N-terminal-pro B-type natriuretic peptide significantly predicted the complicated pulmonary embolism with an area under the receiver operative curve of 0.72 (0.58–0.83) (P<0.05), whereas troponin I did not [area under the receiver operative curve of 0.58 (0.42–0.71)]. Conclusion Unlike troponin I, N-terminal-pro B-type natriuretic peptide may be an accurate marker of in-hospital complication after pulmonary embolism.

Pericardial cardiac troponin I release after coronary artery bypass grafting.

UNLABELLED Pericardial fluid can reflect the composition of cardiac interstitium in myocardial ischemia. This study investigated the hypothesis that pericardial cardiac troponin I (CTnI) measurements could be a more accurate marker of perioperative myocardial infarction (MI) than serum CTnI after coronary artery bypass grafting (CABG). Postoperative arterial and pericardial blood samples were taken in 102 subjects undergoing elective CABG allocated to one of three groups according to the 12-lead electrocardiogram (ECG) abnormalities observed during the first postoperative 24 h: Group 1 = normal ECG; Group 2 = nonspecific ECG abnormalities; and Group 3 = perioperative Q-wave MI. Peak pericardial CTnI concentrations were much higher than peak serum concentrations in all subjects and significantly greater in Group 3 than in Groups 1 and 2 (1,318 +/- 1,810 ng/mL vs 367 +/- 339 ng/mL and 558 +/- 608 ng/mL, respectively; P < 0.01). However, no significant difference between groups occurred at any time for pericardial/serum CTnI ratios, indicating that time courses of CTnI were not different in pericardial fluid and serum. A significant correlation was found between serum and pericardial CTnI concentrations (R = 0.70, P < 0.001). Pericardial CTnI was not more accurate than serum CTnI in predicting Q-wave MI as shown by the low value of the area under the receiver-operator characteristic curve (= 0.71). Peak and early pericardial CTnI were also not accurate in predicting an increase of serum CTnI greater than a cutoff value of 19 ng/mL. Thus, pericardial CTnI measurements were less useful than serum CTnI measurements in the diagnosis of perioperative MI after CABG. IMPLICATIONS Although cardiac troponin I concentrations were much higher in pericardial fluid than in serum and significantly increased in subjects who experienced perioperative Q-wave myocardial infarction, pericardial cardiac troponin I measurements were of less value than serum cardiac troponin I measurements for the diagnosis of perioperative myocardial infarction after coronary artery bypass grafting and cannot be recommended in routine clinical practice.

Normovolemic hemodilution and lumbar epidural anesthesia.

This randomized study was designed to determine the cardiovascular effects of normovolemic hemodilution and lumbar epidural anesthesia in patients scheduled for vascular surgery. The patients were randomly assigned to three different groups: group 1 (N = 10) included patients undergoing lumbar epidural anesthesia without hemodilution: group 2 (N = 10) consisted of patients with normo-volemic hemodilution without epidural anesthesia: and in group 3 (N = 10) normovolemic hemodilution was produced during lumbar epidural anesthesia. The three groups included several patients with a history of either myocardial infarction or stable mild angina or treated and controlled hypertension. In group 1, the level of epidural anesthesia reached T-9 ± 1. After lumbar epidural anesthesia and 7 mL/kg colloid infusion, pulmonary capillary wedge pressure increased slightly but significantly above baseline, without significant changes either in mean arterial pressure or in cardiac index. In group 2, the same colloid infusion as in group 1 when infused before normovolemic hemodilution increased pulmonary capillary wedge pressure and cardiac index without significant effects on arterial blood pressure. Normovolemic hemodilution using a colloid solution decreased hemoglobin concentration (18%) and increased cardiac index significantly (9%). No significant change in systemic oxygen transport or in total body oxygen consumption was observed, In group 3, with anesthesia to T-9 ± 1, hemodynamic changes were as observed in group 1. After normovolemic hemodilution, hemoglobin concentration decreased significantly (15%), whereas cardiac index increased significantly (15%) without significant changes either in mean arterial pressure or in heart rate. Systemic oxygen transport and total body oxygen consumption did not change significantly. No patient experienced chest pain or electro-cardiographic evidence of myocardial ischemia. These data demonstrate that the effects of normovolemic hemodilution during lumbar epidural anesthesia on hemodynamic function and oxygenation were minimal, well tolerated, and comparable to those seen during hemodilution alone.