Hideaki Imanaka

Ventilator-Induced Lung Injury Is Associated with Neutrophil Infiltration, Macrophage Activation, and TGF-β1 mRNA Upregulation in Rat Lungs

Activated neutrophils contribute to the development of ventilator-induced lung injury (VILI) caused by high-pressure mechanical ventilation. However, exact cellular and molecular mechanisms have not been conclusively studied. Our investigation aimed to examine expression of adhesion molecules by both neutrophils and macrophages in lung lavage fluids of rats with VILI. Further, involvement of proinflammatory (tumor necrosis factor-alpha) and profibrogenetic (transforming growth factor-beta 1) mediators was analyzed at mRNA level in lung tissue. Wistar rats were ventilated by high pressure (45 cm H(2)O of peak inspiratory pressure, n = 23) or low pressure (7 cm H(2)O, n = 13) with 0 positive end-expiratory pressure. After 40 min of comparative ventilation, lung lavage was performed in 20 rats from the experimental group and 10 from the control for immunofluorescence analysis with anti-Mac-1 and anti-ICAM-1 monoclonal antibodies. The lung tissues from remaining rats were subjected to pathological and reverse transcription-polymerase chain reaction examinations. Although there was no significant change of PaO(2) in the low-pressure group, PaO(2) was decreased in the high-pressure group. The high-pressure group also had greater neutrophil infiltration into alveolar spaces, upregulation of CD54 and CD11b on alveolar macrophages, and more transforming growth factor-beta 1 mRNA in lung tissues. Tumor necrosis factor-alpha was not involved in the pathogenesis of the severe VILI observed. Histologic findings also demonstrated more infiltrating neutrophils, destructive change of the alveolar wall, and deposition of matrix in the high-pressure group. These results suggest that a series of proinflammatory reactions and profibrogenetic process may be involved in the course of VILI.

Autotriggering caused by cardiogenic oscillation during flow-triggered mechanical ventilation.

Objectives: We noticed that in some patients after cardiac surgery, when flow triggering was used, cardiogenic oscillation might be autotriggering the ventilatory support. In a prospective study, we evaluated the degree of cardiogenic oscillation and the frequency rate of autotriggering. We suspected that autotriggering caused by cardiogenic oscillation was more common than clinically appreciated. Design: Prospective, nonrandomized, clinical study. Setting: Surgical intensive care unit in a national heart institute. Patients: A total of 104 adult patients were enrolled after cardiac surgery. Interventions: During the study period, patients were paralyzed and ventilated with intermittent mandatory ventilation at a rate of 10 breaths/min, pressure support of 10 cm H2O, and flow triggering with a sensitivity of 1 L/min. Measurements and Main Results: Because the patients would not be able to breathe spontaneously, we counted pressure‐support (PS) breaths as instances of autotriggering. Then, we classified the patients into two groups according to the number of PS breaths: an “AT group” (PS breaths of >5/min) and a “non‐AT group” (PS breaths of ≤5/min). If autotriggering occurred, we decreased the sensitivity so autotriggering disappeared (threshold triggering sensitivity). The intensity of cardiogenic oscillation was assessed as the flow and airway pressure at the airway opening. A total of 23 patients (22%) demonstrated more than five autotriggered breaths/min. During mechanical ventilation, the inspiratory flow fluctuation caused by cardiogenic oscillation was significantly greater in the AT group than in the non‐AT group (4.67 ± 1.26 L/min vs. 2.03 ± 0.86 L/min; p < .01). The AT group also showed larger cardiac output, higher ventricular filling pressures, larger heart size, and lower respiratory system resistance than the non‐AT group. As the inspiratory flow fluctuation caused by cardiogenic oscillation increased, the level of triggering sensitivity also was increased to avoid autotriggering. In the AT group with 1 L/min of sensitivity, the respiratory rate increased (19.9 ± 2.7 vs. 10 ± 0 breaths/min, p < .01), PaCO2 decreased (30.8 ± 4.0 torr [4.11 ± 0.36 kPa] vs. 37.6 ± 4.3 torr [5.01 ± 0.57 kPa]; p < .01), and mean esophageal pressure increased (7.7 ± 3.0 vs. 6.9 ± 3.0 cm H2O; p < .01) compared with the threshold triggering sensitivity. Conclusions: Autotriggering caused by cardiogenic oscillation is common in postcardiac surgery patients when flow triggering is used. Autotriggering occurred more often in patients with more dynamic circulation. Autotriggering caused respiratory alkalosis and hyperinflation of the lungs.

Inaccuracies of Nitric Oxide Delivery Systems during Adult Mechanical Ventilation

Background Various systems to administer inhaled nitric oxide (NO) have been used in patients and experimental animals. We used a lung model to evaluate five NO delivery systems during mechanical ventilation with various ventilatory patterns. Methods An adult mechanical ventilator was attached to a test lung configured to separate inspired and expired gases. Four injection systems were evaluated with NO injected either into the inspiratory circuit 90 cm proximal to the Y piece or directly at the Y piece and delivered either continuously or only during the inspiratory phase. Alternatively, NO was mixed with air using a blender and delivered to the high‐pressure air inlet of the ventilator. Nitric oxide concentration was measured from the inspiratory limb of the ventilator circuit and the tracheal level using rapid‐ and slow‐response chemiluminescence analyzers. The ventilator was set for constant‐flow volume control ventilation, pressure control ventilation, pressure support ventilation, or synchronized intermittent mandatory ventilation. Tidal volumes of 0.5 l and 1 l were evaluated with inspiratory times of 1 s and 2 s. Results The system that premixed NO proximal to the ventilator was the only one that maintained constant NO delivery regardless of ventilatory pattern. The other systems delivered variable NO concentration during pressure control ventilation and spontaneous breathing modes. Systems that injected a continuous flow of NO delivered peak NO concentrations greater than the calculated dose. These variations were not apparent when a slow‐response chemiluminescence analyzer was used. Conclusions NO delivery systems that inject NO at a constant rate, either continuously or during inspiration only, into the inspiratory limb of the ventilator circuit produce highly variable and unpredictable NO delivery when inspiratory flow is not constant. Such systems may deliver a very high NO concentration to the lungs, which is not accurately reflected by measurements performed with slow‐response analyzers.

Effect of Ventilatory Settings on Accuracy of Cardiac Output Measurement Using Partial CO2 Rebreathing

Background Recently, a new device has been developed to measure cardiac output noninvasively using partial carbon dioxide (CO2) rebreathing. Because this technique uses CO2 rebreathing, the authors suspected that ventilatory settings, such as tidal volume and ventilatory mode, would affect its accuracy: they conducted this study to investigate which parameters affect the accuracy of the measurement. Methods The authors enrolled 25 pharmacologically paralyzed adult post–cardiac surgery patients. They applied six ventilatory settings in random order: (1) volume-controlled ventilation with inspired tidal volume (VT) of 12 ml/kg; (2) volume-controlled ventilation with VT of 6 ml/kg; (3) pressure-controlled ventilation with VT of 12 ml/kg; (4) pressure-controlled ventilation with VT of 6 ml/kg; (5) inspired oxygen fraction of 1.0; and (6) high positive end-expiratory pressure. Then, they changed the maximum or minimum length of rebreathing loop with VT set at 12 ml/kg. After establishing steady-state conditions (15 min), they measured cardiac output using CO2 rebreathing and thermodilution via a pulmonary artery catheter. Finally, they repeated the measurements during pressure support ventilation, when the patients had restored spontaneous breathing. The correlation between two methods was evaluated with linear regression and Bland-Altman analysis. Results When VT was set at 12 ml/kg, cardiac output with the CO2 rebreathing technique correlated moderately with that measured by thermodilution (y = 1.02x, R = 0.63; bias, 0.28 l/min; limits of agreement, −1.78 to +2.34 l/min), regardless of ventilatory mode, oxygen concentration, or positive end-expiratory pressure. However, at a lower VT of 6 ml/kg, the CO2 rebreathing technique underestimated cardiac out-put compared with thermodilution (y = 0.70x; R = 0.70; bias, −1.66 l/min; limits of agreement, −3.90 to +0.58 l/min). When the loop was fully retracted, the CO2 rebreathing technique overestimated cardiac output. Conclusions Although cardiac output was underreported at small VT values, cardiac output measured by the CO2 rebreathing technique correlates fairly with that measured by the thermodilution method.

Ocular Surface Disorders in the Critically Iii

Abnormalities of the cornea and conjunctiva occur in association with neurological diseases, nocturnal lagophthalmos, coma, infection, and mechanical ventilation.We investigated the incidence and causes of ocular surface disorders in critically ill patients. In a retrospective study, the presence of conjunctivitis and corneal erosion was determined by reviewing the medical charts of 143 mechanically ventilated patients (intensive care unit [ICU] stay >or=to7 days). In the subsequent prospective study, 15 patients who had sedatives or muscle relaxants administered continuously for more than 48 h in the ICU were investigated. Corneal erosion was examined using a slit lamp once a day. Ocular surface disorder was found in 28 of the 143 patients (20%) whose ICU stay exceeded 7 days. The incidence increased with continuous sedation (35% vs 15%). The incidence also increased with continuous neuromuscular blockade (39% vs 11%). In the prospective study, nine patients (60%) developed corneal erosion. A patients inability to fully close his or her eyes increased the incidence (P < 0.01) of corneal erosion. Protective eyelid taping was effective in preventing and treating the corneal erosion. In conclusion, the critically ill often develop ocular surface disorders, especially when sedated and immobilized. A close relationship was observed between these conditions and the inability to close ones eyes. (Anesth Analg 1997;85:343-6)

Effects of norepinephrine on renal function in septic patients with normal and elevated serum lactate levels

Effects of iv norepinephrine (NE) on renal function were investigated retrospectively in 15 patients with hyperdynamic septic shock. All patients had either a low systolic BP less than 80 mm Hg, and/or oliguria less than 0.5 ml/kg-h. We examined their serum creatinine level (SCr), daily urine flow (UF), 24-h creatinine clearance (Ccr), and hemodynamic indices before and during NE infusion. Before NE administration, the patients were divided into those with with a serum lactate level (Lac) less than 20 mg/dl (group A, n = 9) and greater than 20 mg/dl (group B, n = 6). NE was infused continuously at rates between 0.05 and 0.24 microgram/kg.min which increased systolic BP by greater than or equal to 20 mm Hg. Cardiac index was not significantly changed in either group. In group A, NE increased both UF (p less than .05), and systemic vascular resistance index (SVRI) (p less than .01), but did not affect Ccr. In group B, NE did not increase UF nor SVRI, and decreased Ccr significantly (p less than .05). It is concluded that NE increased UF and SVRI only when Lac was in normal range; otherwise, NE reduced renal function. Thus, when administering NE to increase UF, both Lac and renal function should be monitored carefully.

Noninvasive Cardiac Output Measurement Using Partial Carbon Dioxide Rebreathing Is Less Accurate at Settings of Reduced Minute Ventilation and when Spontaneous Breathing Is Present

Background Although evaluation of cardiac output by the partial carbon dioxide rebreathing technique is as accurate as thermodilution techniques under controlled mechanical ventilation, it is less accurate at low tidal volume. It is not clear whether reduced accuracy is due to low tidal volume or low minute ventilation. The effect of spontaneous breathing on the accuracy of partial carbon dioxide rebreathing measurement has not been fully investigated. The objectives of the current study were to investigate whether tidal volume or minute ventilation is the dominant factor for the accuracy, and the accuracy of the technique when spontaneous breathing effort is present. Methods The authors enrolled 25 post–cardiac surgery patients in two serial protocols. First, the authors applied three settings of controlled mechanical ventilation in random order: large tidal volume (12 ml/kg), the same minute ventilation with a small tidal volume (6 ml/kg), and 50% decreased minute ventilation with a small tidal volume (6 ml/kg). Second, when the patient recovered spontaneous breathing, the authors applied three conditions of partial ventilatory support in random order: synchronized intermittent mandatory ventilation–pressure support ventilation, pressure support ventilation with an appropriately adjusted rebreathing loop, and pressure support ventilation with the shortest available loop. After establishing steady state conditions, the authors measured cardiac output using both partial carbon dioxide rebreathing and thermodilution methods. The correlation between the data yielded by the two methods was determined by Bland-Altman analysis and linear regression. Results Cardiac output with the carbon dioxide rebreathing technique correlated moderately with that measured by thermodilution when minute ventilation was set to maintain normocapnia, regardless of tidal volumes. However, when minute ventilation was set low, the carbon dioxide rebreathing technique underreported cardiac output (y = 0.70x; correlation coefficient, 0.34; bias, −1.73 l/min; precision, 1.27 l/min; limits of agreement, −4.27 to +0.81 l/min). When there was spontaneous breathing, the correlation between the two cardiac output measurements became worse. Carbon dioxide rebreathing increased spontaneous tidal volume and respiratory rate (20% and 30%, respectively, during pressure support ventilation) when the rebreathing loop was adjusted for large tidal volume. Conclusions During controlled mechanical ventilation, minute ventilation rather than tidal volume affected the accuracy of cardiac output measurement using the partial carbon dioxide rebreathing technique. When spontaneous breathing is present, the carbon dioxide rebreathing technique is less accurate and increases spontaneous tidal volume and respiratory rate.

The impact of diabetic retinopathy on long-term outcome following coronary artery bypass graft surgery

OBJECTIVES We sought to assess the impact of diabetic retinopathy on long-term outcome among patients with diabetes and multivessel coronary artery disease (MVD) following coronary artery bypass graft surgery (CABG). BACKGROUND For diabetics, CABG is the preferred revascularization strategy. Diabetic retinopathy is a major microvascular complication of diabetes, and its severity is directly related to total glycemic exposure. METHODS We identified 223 consecutive diabetics with MVD whose retinae were evaluated within one year prior to CABG. The most recent ophthalmologic records up until the time of CABG were used to evaluate the severity of retinopathy. The median follow-up after CABG was 11.6 years. RESULTS Diabetic retinopathy was a strong independent predictor of overall mortality (relative risk [RR], 4.0), and repeat revascularization (RR, 3.0). In separate analyses of diabetics with retinopathy and without retinopathy, predictors of mortality differed significantly between the two groups. Among diabetics with retinopathy, the presence of either preoperative renal (RR, 2.5) or ventricular (RR, 2.0) dysfunction had unfavorable effects on mortality, but the survival curves did not differ significantly according to the presence or absence of internal thoracic artery (ITA) grafting. In comparison, among diabetics without retinopathy, ITA grafting (RR, 0.34) had a beneficial effect on mortality, and the survival curves varied somewhat according to the presence or absence of renal or ventricular dysfunction. CONCLUSIONS Diabetics with retinopathy had a distinct post-CABG course with a worse long-term prognosis, as compared with diabetics without retinopathy. Retina evaluation is useful for prediction of long-term prognosis and management of diabetics who need CABG.

Effect of High Flow Nasal Cannula on Thoraco-abdominal Synchrony in Adult Critically Ill Patients

BACKGROUND: High-flow nasal cannula (HFNC) creates positive oropharyngeal airway pressure and improves oxygenation. It remains unclear, however, whether HFNC improves thoraco-abdominal synchrony in patients with mild to moderate respiratory failure. Using respiratory inductive plethysmography, we investigated the effects of HFNC on thoraco-abdominal synchrony. METHODS: We studied 40 adult subjects requiring oxygen therapy in the ICU. Low-flow oxygen (up to 8 L/min) was administered via oronasal mask for 30 min, followed by HFNC at 30–50 L/min. Respiratory inductive plethysmography transducer bands were circumferentially placed: one around the rib cage, and one around the abdomen. We measured the movement of the rib-cage and abdomen, and used the sum signal to represent tidal volume (VT) during mask breathing, and at 30 min during HFNC. We calculated the ratio of maximum compartmental amplitude (MCA) to VT, and the phase angle. We assessed arterial blood gas and vital signs at each period, and mouth status during HFNC. We used multiple regression analysis to identify factors associated with improvement in thoraco-abdominal synchrony. RESULTS: During HFNC, breathing frequency significantly decreased from 25 breaths/min (IQR 22–27 breaths/min) to 21 breaths/min (IQR 18–24 breaths/min) (P < .001), and MCA/VT (P < .001) and phase angle (P = .047) significantly improved. CONCLUSIONS: HFNC improved thoraco-abdominal synchrony in adult subjects with mild to moderate respiratory failure.

Value of Mild Hypothermia in Patients Who Have Severe Circulatory Insufficiency Even After Intra-Aortic Balloon Pump

STUDY OBJECTIVE To evaluate the effectiveness of mild hypothermia in postcardiac surgical patients with severe heart failure in spite of conventional medical therapy and the use of intra-aortic balloon pumping (IABP). DESIGN Prospective, clinical study. SETTING Teaching hospital. PATIENTS 10 postcardiac surgical patients with severe heart failure despite the use of IABP with massive doses of catecholamine. INTERVENTIONS Patients underwent mild hypothermia produced by surface cooling (to approximately 34.5 degrees C). Hemodynamic criteria for the induction of hypothermia included a cardiac index (CI) of less than 2.2 L/min/m2 with a pulmonary capillary wedge pressure (PCWP) of up to 18 mmHg despite the use of IABP with massive doses of catecholamine. MEASUREMENTS AND MAIN RESULTS After control measurements had been taken at normal core body temperature (37 degrees C), patients were cooled to approximately 34.5 degrees C (using a cooling blanket and gastric lavage with cold water) to decrease tissue oxygen (O2) demand. Patients showed significant improvements in CI (1.9 +/- 0.3 to 2.2 +/- 0.3 L/min/m2), mixed venous O2 saturation, (SvO2; 55 +/- 7 to 64 +/- 6%), and urine output (2.1 +/- 1.1 to 3.4 +/- 2.2 ml/kg/hr). Patients were rewarmed while SvO2 was being monitored. The duration of the hypothermia was 38 +/- 41 hours. Oxygen delivery increased in 8 of the 10 patients, the mean value (+/- SD) for the group rising from 309 +/- 65 ml/min/m2 to 358 +/- 57 ml/min/m2 as temperature was reduced from 36.7 +/- 0.4 degrees C to 34.7 +/- 0.3 degrees C. All patients were successfully weaned from IABP at 140 +/- 107 hours after admission to the intensive care unit. CONCLUSIONS Mild hypothermia is a simple and useful procedure for improving the circulation of postcardiac surgical patients with severe heart failure despite the use of IABP.