Surface electromyographic evaluation of the neuromuscular activation of the inspiratory muscles during progressively increased inspiratory flow under inspiratory-resistive loading.

This study aimed to evaluate neuromuscular activation in the scalene and sternocleidomastoid muscles using surface electromyography (EMG) during progressively increased inspiratory flow, produced by increasing the respiratory rate under inspiratory-resistive loading using a mask ventilator. Moreover, we attempted to identify the EMG inflection point (EMGIP) on the graph, at which the root mean square (RMS) of the EMG signal values of the inspiratory muscles against the inspiratory flow velocity acceleration abruptly increases, similarly to the EMG anaerobic threshold (EMGAT) reported during incremental-resistive loading in other skeletal muscles. We measured neuromuscular activation of healthy male subjects and found that the inspiratory flow velocity increased by approximately 1.6-fold. We successfully observed an increase in RMS that corresponded to inspiratory flow acceleration with ρ ≥ 0.7 (Spearman's rank correlation) in 17 of 27 subjects who completed the experimental protocol. To identify EMGIP, we analyzed the fitting to either a straight or non-straight line related to the increasing inspiratory flow and RMS using piecewise linear spline functions. As a result, EMGIP was identified in the scalene and sternocleidomastoid muscles of 17 subjects. We believe that the identification of EMGIP in this study infers the existence of EMGAT in inspiratory muscles. Application of surface EMG, followed by identification of EMGIP, for evaluating the neuromuscular activation of respiratory muscles may be allowed to estimate the signs of the respiratory failure, including labored respiration, objectively and non-invasively accompanied using accessory muscles in clinical respiratory care.

Effects of diltiazem on in vitro cardiovascular actions of crude venom obtained from Okinawan box-jellyfish (Habu-kurage), Chiropsalmus quadrigatus.

The venom obtained from Okinawan box-jellyfish (Habu-kurage), Chiropsalmus quadrigatus, produced increases in contractions of isolated rat right atrial preparations in a concentration-dependent manner without changes in a spontaneous beating rate. These increases in contractions were significantly inhibited by diltiazem and did not show tachyphylaxis. The venom also produced increases in contractions of isolated rat aortic ring preparations (endothelium-intact) in a concentration-dependent fashion, which were reproducible with repeated application and were significantly inhibited by diltiazem or heating. These increases in vascular contractions were weakened in endothelium-denuded preparations, and almost abolished in a calcium-free medium. On the other hand, the venom at higher concentrations diminished contractions of both myocardial and vascular preparations and did not show reproducibility. These results suggest that the Habu-kurage venom is heat-labile and may increase contractions of cardiac muscle and aortic smooth muscle by increasing calcium influx into muscle cells, and that the venom at higher concentrations may produce dysfunction of muscle contractile systems due to calcium overload.

[Inhaled nitric oxide therapy].

Inhaled nitric oxide (INO) therapy is becoming an indispensable measure in some critically ill patients with pulmonary hypertension. Most importantly, it has been shown that INO significantly reduces the necessity for extracorporeal lung assist in newborns with hypoxemic respiratory failure and pulmonary hypertension. A large number of basic and clinical studies are making great steps in delineating its physiology, techniques, side effects, and clinical efficacy. This article reviews the current knowledge of INO therapy including a novel device of nitric oxide production system.

Combination of inhaled nitric oxide therapy and inverse ratio ventilation in patients with sepsis-associated acute respiratory distress syndrome.

Inverse ratio ventilation (IRV) is a ventilatory technique that uses an inspiratory to expiratory ratio (I:E) greater than 1:1. We studied the effects of mechanical ventilation with an I:E of 1:3, 1:1, and 2:1 on arterial oxygenation in 10 patients with sepsis-associated acute respiratory distress syndrome (ARDS). At each I:E, patients received 0 and 4 ppm of inhaled nitric oxide (INO) in random order for 30 min. Respiratory and cardiovascular parameters were measured. Of the 10 patients studied, 7 responded to IRV and 3 did not. An increase in the I:E and the addition of INO significantly improved arterial oxygenation in the responders (p < 0. 0001 and p < 0.006, respectively). The combination of an increase in the I:E and INO had an additive effect on arterial oxygenation. The combined use of IRV and INO is a more effective method of avoiding hypoxemia than either INO or IRV alone.

Combined effects of inhaled nitric oxide and positive end-expiratory pressure during mechanical ventilation in acute respiratory distress syndrome.

We studied the combined effects of inhaled nitric oxide (INO) and positive end expiratory pressure (PEEP) during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Eleven patients received 0 and 4 parts per million of INO in random order for 30 min at PEEP levels of 0, 5, and 10 cm H2O. Respiratory and cardiovascular parameters were measured. The addition of INO and PEEP significantly improved arterial oxygenation (p < 0.005 and p < 0.0001, respectively). The combined effect of INO and PEEP on arterial oxygenation was remarkable during 10 cm H2O PEEP. There was synergistic effect on arterial oxygenation by combining INO and 10 cm H2O PEEP. The present study showed that the combination of INO and 10 cm H2O PEEP enhanced arterial oxygenation in patients with ARDS.

Evaluation of oxygen consumption and resting energy expenditure in critically ill patients with systemic inflammatory response syndrome.

OBJECTIVE: To determine whether oxygen consumption VO2), CO2 production, and resting energy expenditure (REE) in critically ill patients differ in varying grades of systemic inflammatory response syndrome (SIRS). DESIGN: Prospective, clinical study. SETTING: Intensive care unit at a university hospital. PATIENTS: Twenty-six critically ill patients requiring mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 100 metabolic measurements were performed. The grade of SIRS and the Acute Physiology and Chronic Health Evaluation II score were evaluated at the time of the metabolic cart study. VO2 and REE differed among the groups inadequate for SIRS (non-SIRS), with SIRS without infection (nonseptic SIRS), and with SIRS with infection (septic SIRS) (125 +/- 37 mL/min/m2 and 855 +/- 204 kcal/day/m2, 135 +/- 33 mL/min/m2 and 948 +/- 214 kcal/day/m2, and 166 +/- 55 mL/min/m2 and 1149 +/- 339 kcal/day/m2, respectively; p < .005). Patients with septic SIRS had higher VO2 and REE than patients with non-SIRS and nonseptic SIRS. CONCLUSION: VO2 and REE differ among groups of patients with non-SIRS, nonseptic SIRS, and septic SIRS. Patients with septic SIRS have higher VO2 and REE than patients with non-SIRS or nonseptic SIRS. The present study shows that classifying patients into three grades (non-SIRS, nonseptic SIRS, and septic SIRS) is a valid predictor of metabolic stress in critically ill patients.

The pharmacokinetics of ceftazidime during hemodiafiltration in critically ill patients.

We studied the pharmacokinetics of ceftazidime in 3 critically ill patients undergoing continuous hemodiafiltration (CHDF). Blood samples were obtained from both the arterial and venous sites of the CHDF system 0, 1, 2, 4, 6, and 12 h after the start of ceftazidime administration. Pharmacokinetic variables were calculated by fitting individual concentration-time curves to a two-compartment open model. The elimination phase half-life was 6.86 h, and the total elimination rate constant was 0.17 h(-1). Six hours after the start of administration, the ceftazidime concentration in the arterial site decreased from the peak level of 77.5+/-31.4 (mean+/-standard deviation [SD]) microg/ml to 26.2+/-2.5 microg/ml. The ceftazidime concentration examined in 2 cases decreased to 14.7+/-5.8 microg/ml after 12 h. The results suggested that ceftazidime should be administered at 1 g/day in patients with severe infection during CHDF.

[Nitric oxide inhalation as an effective therapy for acute respiratory distress syndrome due to near-drowning: a case report].

A 16-year-old boy with acute respiratory distress syndrome (ARDS) due to near-drowning was admitted to our hospital. ARDS was treated with low-level nitric oxide (NO) inhalation (ranging from 4 ppm to 1 ppm) for 24 days. Oxygenation was improved and pulmonary hypertension was reduced after NO inhalation, but systemic blood pressure, heart rate, and cardiac output were not affected. PaO2 improved from 153 Torr to 354 Torr under identical ventilating conditions (F1O2 1.0), and mean pulmonary arterial pressure fell from 40 mm Hg to 27 mmHg. It has been reported that NO inhalation alleviates ventilation-flow mismatch and pulmonary hypertension. It is unclear, however, whether this therapy improves the prognosis for ARDS. In our patient, NO inhalation was effective in alleviating the oxygenation impairment and pulmonary hypertension associated with ARDS.

Efficacy of inhaled nitric oxide in children with ARDS.

STUDY OBJECTIVE: Data concerning inhaled nitric oxide (iNO) on pediatric ARDS is rare. We investigated the effects of iNO on pediatric ARDS in order to examine the ability to predict a response to iNO, the optimal concentration of iNO, the effects of < or = 1 ppm nitric oxide (NO), and the effect of iNO on PaCO2. SETTING: ICU at Kumamoto (Japan) University Hospital. PATIENTS AND INTERVENTIONS: Seven children with ARDS. The initial responses to 16 ppm NO and the dose-response effects of 0.13 to 16 ppm NO were assessed. MEASUREMENTS AND RESULTS: Sixteen ppm of iNO improved oxygenation in all seven children. The use of iNO significantly increased the ratio of arterial oxygen tension to the fraction of inspired oxygen (PaO2/FIO2). A correlation between the NO-induced increase in PaO2/FIO2 and the baseline PaO2/FIO2 was observed (r=0.93, p<0.01). Dose-response tests showed that the optimal concentration of iNO was < or = 4 ppm, improvements in PaO2/FIO2 could be observed with concentrations of < or = 1 ppm NO, and iNO induced a slight decrease in PaCO2. CONCLUSIONS: In children with ARDS, iNO frequently improves oxygenation and induces a slight decrease in PaCO2, with the baseline PaO2/FIO2 functioning as a predictor of all NO response. Improvements of PaO2 and PaCO2 were observed with concentrations of iNO of < or = 1 ppm, a level in which the risk of a toxic reaction in children is minimal. Effects on outcome need verification in larger controlled trials.

Inhaled nitric oxide followed by extracorporeal membrane oxygenation in resuscitating a newborn with hypoxemia.

In a newborn requiring cardiopulmonary resuscitation because of hypoxemia due to sepsis (oxygenation index > 40), inhalation of nitric oxide (NO) in a concentration of 16 p.p.m. improved oxygenation and restored spontaneous circulation. Cannulation for extracorporeal membrane oxygenation (ECMO) then was performed safely under NO inhalation. ECMO was discontinued on day 7, and on day 14 the infant was extubated. During follow-up examination at 5 months of age no neurological abnormalities were found. This case shows the usefulness of combining inhaled NO and ECMO.

Emergency extracorporeal life support for patients with near-fatal status asthmaticus.

Extracorporeal life support (ECLS) was used to treat three patients with near-fatal status asthmaticus who did not respond to aggressive medical therapies and mechanical ventilation under controlled permissive hypercapnia. ECLS was instituted in patient 1 because PaCO2 was excessively high and pH was excessively low, in patient 2 because hypoxemia and shock were not responsive to treatment, and in patient 3 because of sustained severe hypotension. ECLS supported adequate gas exchange until pulmonary function improved, diminishing the need for mechanical ventilation and preventing pulmonary complications. Pulmonary dysfunction improved markedly after only 21 to 86 hours of ECLS. Aggressive medical treatments were continued during ECLS. Our findings indicate that ECLS is a useful method for preventing death in patients with near-fatal status asthmaticus.

Nitrogen dioxide production in a nitric oxide inhalation system using the Servo Ventilator 900C.

During nitric oxide (NO) inhalation therapy, toxicity may be produced by the reactive metabolite nitrogen dioxide (NO2). The purpose of the present study was to determine the NO2 concentration in a NO inhalation system used for respiratory failure in children at relatively low concentrations of NO (< 20 ppm). The production of NO2 in the NO inhalation system using the Servo Ventilator 900C connected to the test lung under each of 30 combinations of NO concentrations (0, 4, 8, 12, 16, and 19 ppm) and inspired oxygen (O2) concentrations (21, 40, 60, 80, and 100%). Pressure controlled ventilation was used with a respiratory rate of 20 breaths/min. NO and NO2 measurements were obtained on the inspiratory side of the Y-piece connected to the test lung. At a given NO level, increases in the concentration of inspired O2 resulted in increases in the concentration of NO2 produced, as did increases in the amount of NO at a given concentration of O2. The mean NO concentration at the inspiratory site of the Y-piece did not exceed 0.05 ppm (the limit of NO2 as an outdoor air pollutant in the United States) when the NO concentration did not exceed 8 ppm, regardless of the O2 concentration. NO inhalation therapy for children with severe respiratory failure using the Servo Ventilator 900C can be performed safely when the concentration of NO does not exceed 8 ppm.

The safety of a nitric oxide inhalation system with high frequency oscillatory ventilation.

Nitric oxide (NO) inhalation and high frequency oscillatory ventilation (HFOV) has been indicated in infants with severe respiratory failure. The purpose of the present study was to evaluate the safety of an NO inhalation system with HFOV in terms of nitrogen dioxide (NO2) production. The NO inhalation system consisted of a high frequency oscillatory ventilator, a neonatal circuit and a test lung. The NO concentration was changed from 0 to 19 p.p.m. At each level of NO, the oxygen (O2) concentration was changed from 21 to 100%. The NO and NO2 concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO2 concentration was increased when either the O2 or the NO concentration was increased. The interposition of the endotracheal tubes increased NO2 concentrations at 4 p.p.m. NO. The high stroke volume and high mean airway pressure produced a significant increase in NO2 production at 4 p.p.m. NO. The increase in NO2 production was prevented by placing a one-way valve at the joint of the NO gas line to the inspired limb. It was concluded that the NO inhalation system with HFOV can be safely used when a one-way valve is placed at the joint of the NO gas line to the inspired limb and when inhaled NO is at a relatively low concentration.

The safety of a nitric oxide inhalation system using a conventional infant respirator.

Attention is becoming increasingly focused on inhalation of nitric oxide (NO) as a selective pulmonary vasodilator. Its metabolite nitrogen dioxide (NO2), however, is a toxic molecule. The purpose of the present study was to evaluate the safety of a NO inhalation system using a conventional infant respirator from the viewpoint of NO2 production. The NO inhalation system consisted of a standard neonatal ventilator, a neonatal circuit and a test lung. The NO concentration was increased from 0 up to 19 ppm. At each level of NO, the oxygen (O2) concentration was changed from 21 to 100%. The NO and NO2 concentrations were measured with a chemiluminescence analyzer using a molybdenum converter. The NO2 concentration was increased when either the O2 or the NO concentration was increased. The maximum concentration of NO2 was 0.10 +/- 0.02 ppm when the concentrations of NO and O2 were 19 ppm and 100% respectively. The NO inhalation system, using a conventional infant respirator, can be used safely when monitoring NO and NO2 concentrations.

[Endobronchial treatments made possible by extracorporeal lung assist in a patient in status asthmaticus refractory to mechanical ventilation].

A 19-year-old endotracheally intubated women was admitted to our hospital in severe status asthmaticus that was not relieved by inhalation of beta 2-agonists or by epinephrine, aminophylline, or corticosteroids. A chest radiography revealed pneumomediastinum and subcutaneous emphysema. Pressure-limited mechanical ventilation at a peak airway pressure of 20--30 cmH2O failed to ventilate the lungs, and caused a left pneumothorax and atelectasis. Extracorporeal lung assist (ECLA) was begun and enabled repeated suctioning through a fiberoptic bronchoscope for more than a minute with no serious complications. During ECLA aerosol therapy with a large dose of a beta 2-agonist (procatherol 0.15 mg) increased the tidal volume with no adverse effects. Atelectatic areas of the lungs re-expanded, pulmonary function improved, and ECLA was stopped 86 hours after it had been started. We suggest that, although it is highly invasive, ECLA can be useful in patients with status asthmaticus refractory to mechanical ventilation, and can allow endobronchial suctioning to be done safely.

Evaluation of Mapleson systems for administration of inhaled nitric oxide.

To assess the safety of nitric oxide (NO) inhalation during manual-controlled ventilation using Mapleson A, D, and F systems, we examined nitrogen dioxide (NO2) production using a chemiluminescence analyzer. The NO concentration was changed from 0 to 19 parts per million (ppm), and at each level of NO the oxygen (O2) concentration was changed from 21% to 100%. The NO2 concentration was observed to increase when either the O2 or NO concentration was increased. The maximum NO2 concentrations (mean ± standard deviation) of the Mapleson A, D, and F systems were 0.20±0.03, 0.15±0.03, and 0.17±0.02 ppm, respectively, when the concentrations of NO and O2 were 19 ppm and 100%, respectively. The NO2 concentrations of the Mapleson A system were significantly higher than those of either the Mapleson D or F system at 4, 8, and 12 ppm NO and 100% O2, and than that of the Mapleson D system at 19 ppm NO and 100% O2. From the viewpoint of NO2 production, we suggest that the Mapleson D and F systems are safer than the Mapleson A system when manual-controlled ventilation is required.

The determinant of severe cerebral dysfunction in patients undergoing emergency extracorporeal life support following cardiopulmonary resuscitation.

We investigated the factors associated with cerebral dysfunction in patients undergoing extracorporeal life support (ECLS) following conventional advanced cardiac life support (ACLS). The subjects were 9 patients in whom ECLS was started following ACLS because of intractable cardiac arrest. We investigated whether the irreversibility of cerebral dysfunction during ECLS was related to the cardiopulmonary resuscitation (CPR) time, arterial pH and blood gases, hemoglobin concentration (Hb), peak arterial pressure (PAP) before the start of ECLS and total doses of epinephrine and sodium bicarbonate administered during CPR. Two of the 3 patients who recovered consciousness were weaned from ECLS and survived, while all 6 patients who did not recover from coma were not weaned and died. There was no difference in the CPR time, Hb and PAP before the start of ECLS along with total doses of epinephrine and sodium bicarbonate administered during CPR between the patients who recovered consciousness and those who did not. In addition, there was no difference in arterial pH and blood gases except the arterial oxygen tension (PaO2) between the groups. The PaO2 values before the start of ECLS in the patients who remained in coma ranged from 34 to 58 mmHg, whereas those in the patients who recovered consciousness ranged from 132 to 442 mmHg. The PaO2 values before the start of ECLS in the patients who remained in coma were less than 60 mmHg, whereas those in the patients who recovered consciousness were over 60 mmHg. The present study suggests that hypoxemia during CPR may play a major role in severe cerebral dysfunction in patients undergoing ECLS and PaO2 during CPR.

Emergency and long-term extracorporeal life support following acute myocardial infarction: rescue from severe cardiogenic shock related to stunned myocardium.

There has been no report regarding therapy of extracorporeal life support (ECLS) that showed stunned myocardium echocardiographically and electrocardiographically in patients with acute myocardial infarction. ECLS was performed in eight patients with cardiogenic shock or arrest unresponsive to catecholamines and intra-aortic balloon pumping following myocardial infarction; these patients required prolonged external cardiac massage. After the initiation of ECLS, both blood pressure and metabolic acidosis improved in all patients. Four of eight patients were weaned from ECLS after a mean of 69.3 h, which was far longer than previously reported in patients with ischemic heart disease. Three of these patients survived, and cardiac function recovered to NYHA class II in two of the survivors and class III in the other. The other five patients did not recover from coma during ECLS and died. A marked improvement of ventricular wall motion was seen in two survivors with the disappearance of pathologic Q waves after the initiation of ECLS. No occlusion of the coronary arteries or bypass grafts was observed in any of the survivors. These findings suggested the existence of stunned myocardium with myocardial reperfusion. The recovery of stunned myocardium may be delayed for days or even weeks, hence the extended period of ECLS therapy was theoretically justifiable. We conclude that long-term ECLS is a useful therapeutic method for patients with severe cardiogenic shock that is related to stunned myocardium.