PF Ratio Research Articles

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Introduction: The FDA cautions clinicians that the sensitivity (95% CI: 24-91%) and specificity (95% CI: 69-94%) of Rapid Flu A tests in adults are notoriously poor (FDA, 2013). This is the case of an 18-year-old male admitted from the Emergency Department with a negative Rapid Flu test for ARDS suspected as an inhalation injury (bleach inhalation versus illicit inhalant use). Patient presented with fever, cough, vomiting, diarrhea, headaches and tachypnea and was admitted to an intermediate critical care unit with subsequent ICU transfer for respiratory failure and intubation with a PF ratio of 54 and oxygenation index of 46 with groundglass opacities noted on CT. Extubated after a 16-day course of MV requiring heavy sedation for ventilator synchrony, including high-dose paralytic infusions required to achieve a train of four of 3/4. Large pneumomediastinum and pneumoperitoneum on HD 7 with extensive subcutaneous emphysema resolved without intervention on HD19. Flu A viral cultures from a miniBAL on HD 2 were resulted on HD 11 (variant subtyping not available) and treatment with oseltamivir was initiated. Encephalopathic process identified 2 days after extubation with tonic-clonic seizures with deterioration on HD 26 requiring reintubation for airway protection (2 days). MRI suspicious for acute demyelinating encephalomyelitis treated with IVIG. Patient complained of severe headaches on HD 31 with subsequent progressive left-sided weakness, pronator drift, dysmetria, nystagmus and partial visual field loss noted on HD 33 with a CT revealing 7mm right-to-left midline shift and intraparenchymal hemorrhage and edema. Patient is discharged from the hospital with mild cognitive impairment and left-sided neglect with rehabilitation treatment in progress. The clinical consequences of severe influenza-related infection, in this case an off-season case of untyped flu A, can be broad. In addition to severe respiratory compromise, severe CNS complications and sequelae are noted which are not widely reported in the medical literature. Reference: FDA. (2013). Cautions in using rapid tests for detecting Influenza A viruses. Retrieved August 1, 2013, from http://www.fda.gov/MedicalDevices/Safety/AlertsandNotices/TipsandArticlesonDeviceSafety/ucm109385.htm

High frequency oscillation and airway pressure release ventilation in pediatric respiratory failure

Airway pressure release ventilation (APRV) and high frequency oscillatory ventilation (HFOV) are frequently used in acute lung injury (ALI) refractory to conventional ventilation. Our aim was to describe our experience with APRV and HFOV in refractory pediatric ALI, and to identify factors associated with survival. We analyzed 104 patients with hypoxemia refractory to conventional ventilation transitioned to either APRV or HFOV. Demographics, oxygenation index (OI), and PaO2 /FiO2 (PF ratio) were recorded before transition to either mode of nonconventional ventilation (NCV) and for every 12 hr after transition. Relative to APRV, patients on HFOV were younger and had more significant lung disease evidenced by higher OI (28.5 [18.6, 36.2] vs. 21.0 [15.5, 30.0], P = 0.008), lower PF ratios (73 [59,94] vs. 99 [76,131], P = 0.002), and more frequent use of inhaled nitric oxide. In univariate analysis, HFOV was associated with more frequent neuromuscular blockade. Forty-one of 104 patients died on NCV (39.4%). Survivors demonstrated improvement in OI 24 hr after transition to NCV, whereas non-survivors did not (12.9 [8.9, 20.9] vs. 28.1 [17.6, 37.1], P < 0.001). After controlling for immunocompromised status, number of vasopressors, and OI before transition, mode of NCV was not associated with mortality. In a heterogeneous PICU population with hypoxemia refractory to conventional ventilation transitioned to NCV, improvement in oxygenation at 24 hr was associated with survival. Immunocompromised status, number of vasopressor infusions, and the OI before transition to NCV were independently associated with survival.

Indications, durations and outcomes of mechanical ventilation in dogs and cats with tick paralysis caused byIxodes holocyclus: 61 cases (2008–2011)

The primary objectives of this research were to describe the indications for mechanical ventilation, the duration of mechanical ventilation and probability of survival in dogs and cats with respiratory failure induced by the Australian paralysis tick (Ixodes holocyclus). A retrospective case series and a retrospective single cohort study were conducted using dogs and cats with tick paralysis requiring mechanical ventilation. An index of oxygenating performance of the lung (PF ratio of partial pressure of oxygen in arterial blood to fraction of inspired oxygen) was derived from arterial blood gas analysis; patients euthanased because of veterinary costs were identified and Kaplan-Meier survival analyses performed. In total, 36.6% of patients were ventilated because of hypoxaemia refractory to oxygen therapy, 38.3% because of hypoventilation, 18.3% because of unsustainable respiratory effort and 6.6% because of respiratory arrest. Median duration of mechanical ventilation was 23 h, median time hospitalised was 84 h and 63.9% of all patients requiring mechanical ventilation survived to discharge from the hospital. Survival probability increased to 75% when cases of cost-based euthanasia were right-censored rather than treated as deaths. The survival probability of patients ventilated because of hypoxaemia (52.6%) was significantly less than for those ventilated because of hypoventilation (90.5%). The first measured PF ratio after commencing mechanical ventilation was not significantly associated with survival probability. Dogs and cats with tick paralysis requiring mechanical ventilation to manage respiratory failure have reasonable survival probability. Dogs and cats requiring mechanical ventilation because of hypoventilation have a higher survival probability than those with oxygenation failure.

Correlation of oxygen saturation as measured by pulse oximetry/fraction of inspired oxygen ratio with Pao2/fraction of inspired oxygen ratio in a heterogeneous sample of critically ill children

PurposeOxygen saturation as measured by pulse oximetry (Spo2)/fraction of inspired oxygen (Fio2) (SF) ratio has demonstrated to be an adequate marker for lung disease severity in children under mechanical ventilation. We sought to validate the utility of SF ratio in a population of critically ill children under mechanical ventilation, noninvasive ventilation support, and breathing spontaneously. Materials and methodsA retrospective database study was conducted in a pediatric intensive care unit of a university hospital. Children with Spo2 less than or equal to 97% and an indwelling arterial catheter were included. Simultaneous blood gas and pulse oximetry were collected in a database. Derivation and validation data sets were generated, and a linear mixed modeling was used to derive predictive equations. Model performance and fit were evaluated using the validation data set. ResultsThree thousand two hundred forty-eight blood gas and Spo2 values from 298 patients were included. 1/SF ratio had a strong linear association with 1/Pao2/Fio2 (PF) ratio in both derivation and validation data sets, given by the equation 1/SF = 0.00164 + 0.521/PF (derivation). Oxygen saturation as measured by pulse oximetry/Fio2 values for PF criteria of 100, 200, and 300 were 146 (95% confidence interval [CI], 142-150), 236 (95% CI, 228-244), and 296 (95% CI, 285-308). Areas under receiver operating characteristic curves for diagnosis of PF ratio less than 100, 200, and 300 with the SF ratio were 0.978, 0.952, and 0.951, respectively, in the validation data set. ConclusionsOxygen saturation as measured by pulse oximetry/Fio2 ratio is an adequate noninvasive surrogate marker for PF ratio. Oxygen saturation as measured by pulse oximetry/Fio2 ratio may be an ideal noninvasive marker for patients with acute hypoxemic respiratory failure.

Ventilatory strategies in septic patients

Mortality in intensive care unit (ICU) patients is affected by multiple variables. The possible impact of the mode of ventilation has not yet been clarified; therefore, a secondary analysis of the "epidemiology of sepsis in Germany" study was performed. The aims were (1) to describe the ventilation strategies currently applied in clinical practice, (2) to analyze the association of the different modes of ventilation with mortality and (3) to investigate whether the ratio between arterial partial pressure of oxygen and inspired fraction of oxygen (PF ratio) and/or other respiratory variables are associated with mortality in septic patients needing ventilatory support. A total of 454 ICUs in 310 randomly selected hospitals participated in this national prospective observational 1-day point prevalence of sepsis study including 415 patients with severe sepsis or septic shock according to the American College of Chest Physicians/Society of Critical Care Medicine criteria. Of the 415 patients, 331 required ventilatory support. Pressure controlled ventilation (PCV) was the most frequently used ventilatory mode (70.6 %) followed by assisted ventilation (AV 21.7 %) and volume controlled ventilation (VCV 7.7 %). Hospital mortality did not differ significantly among patients ventilated with PCV (57 %), VCV (71 %) or AV (51 %, p=0.23). A PF ratio equal or less than 300 mmHg was found in 83.2 % of invasively ventilated patients (n=316). In AV patients there was a clear trend to a higher PF ratio (204±70 mmHg) than in controlled ventilated patients (PCV 179±74 mmHg, VCV 175±75 mmHg, p=0.0551). Multiple regression analysis identified the tidal volume to pressure ratio (tidal volume divided by peak inspiratory airway pressure, odds ratio OR=0.94, 95 % confidence interval 95% CI=0.89-0.99), acute renal failure (OR=2.15, 95% CI=1.01-4.55) and acute physiology and chronic health evaluation (APACHE) II score (OR=1.09, 95% CI=1.03-1.15) but not the PF ratio (univariate analysis OR=0.998, 95 % CI=0.995-1.001) as independent risk factors for in-hospital mortality. This representative survey revealed that severe sepsis or septic shock was frequently associated with acute lung injury. Different ventilatory modes did not affect mortality. The tidal volume to inspiratory pressure ratio but not the PF ratio was independently associated with mortality.

A rare case of fatal acute respiratory distress syndrome following diesel oil siphonage

Sir, Diesel oil aspiration is an uncommon mode of hydrocarbon aspiration and can lead to severe chemical pneumonitis either due to direct inhalation of aerosol or aspiration of liquid or indirectly following aspiration of vomitus secondary to diesel oil ingestion during the manual siphoning from fuel tanks. Siphonage of fuel from the motor vehicles fuel tanks is a typical practice seen in third world countries. Data are sparse on outcomes and complications of direct diesel oil aspiration following manual siphoning.[12] We report a case of 21-year-old male industrial worker who was admitted to the emergency room with a history of diesel oil ingestion and aspiration following accidental siphoning of oil. He was febrile, dyspneic with altered sensorium and having feeble pulse (pulse rate-124/min) and falling blood pressure (82/40 mmHg). On auscultation of chest, coarse, basal, inspiratory crepitations were heard. Arterial blood gas (ABG) analysis showed severe hypoxemia with metabolic acidosis. In view of deteriorating clinical condition, his trachea was intubated with endotracheal tube and was supported with intravenous fluids and inotropes. He was then shifted to intensive care unit (ICU) for mechanical ventilatory support and further management. In ICU, chest X-ray Anteroposterior view (AP) showed bilateral, non-segmental, homogeneous opacities in the lower zones. There was a significant increase in leukocyte counts (total leukocyte count-16,200/Ul, neutrophills 92%). Empirical broad spectrum antibiotics (piperacillin/tazobactam 4.5 g IV q8h) were immediately started after sending blood and tracheal aspirate for culture and sensitivity. On day 2 in ICU, the patient's clinical condition deteriorated dramatically. Chest X-ray showed bilateral progression of infiltrates involving nearly all lobes of the lungs. ABG analysis showed severely diminished PF ratio (PaO2/ FIO2 < 100). These findings were suggestive of a severe form of acute respiratory distress syndrome (ARDS).[3] Aggressive supportive therapy and low tidal volume ventilation strategy was immediately initiated.[4] We also started a continuous infusion of low dose methylprednisolone (@ 1 mg/kg/day after giving bolus of 1 mg/kg IV). On day 5, he had an episode of pulseless ventricular tachyarrhythmia, unresponsive to all possible resuscitative measures and eventually expired that day. Direct aspiration of hydrocarbons may cause severe chemical (lipoidal) pneumonitis with perilous outcome.[25] The severity of lung tissue damage depends on physical characteristics of hydrocarbon, which includes viscosity, volatility and side chains of hydrocarbons. The probability of severe lung affliction is extensive with hydrocarbons having high volatility and low viscosity (<60 saybolts seconds universal (SSU)).[6] Diesel fuel (grade 1D and 2D) have a low viscosity (32-45 SSU) and is highly volatile and a potential hydrocarbon to cause severe progressive lung damage and fatal ARDS.[6] In early period of hydrocarbon induced pneumonia, patients may have non-specific symptoms such as cough, breathlessness and rarely chest pain or haemoptysis.[7] Later, these patients may develop cardiomyopathies or fatal cardiac arrhythmias.[7] Although right middle lobes are commonly affected by direct aspiration of diesel, chest radiographic findings may include consolidation, atelectasis, pleural effusion and lower lobe involvement as seen in this patient.[128] The management strategies in these patients are usually symptomatic and supportive. There is limited and controversial role of corticosteroids and antibiotics with sparse data on outcomes.[18] This patient showed accelerated deterioration of lung functions and eventually expired due to fatal cardiac arrhythmias within a period of 4 days despite initiating corticosteroids, broad-spectrum antibiotics and strict adherence to ventilator protocols followed in ARDS patients.[4] This case highlights that chemical pneumonitis triggered by direct diesel oil aspiration following manual siphoning is a pernicious clinical condition in which lung damage is progressive and extensive resulting in ARDS, which seldom respond to standard management strategies. Moreover, death can ensue due to fatal cardiac arrhythmias even in early course of the disease. Critical carers should circumspect this rare and fatal clinical condition early in its course and should intervene with aggressive management strategies to avoid cataclysmic outcomes.

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Introduction: Alveoli in the acutely injured lungs may repetitively collapse and expand at expiration having a negative impact on ventilation/perfusion match. Hypothesis: Low tidal ventilation with PEEP optimized to maintain the end-expiratory transpulmonary pressure?0 cmH2O will improve oxygenation and shunt fraction, as compared to strategies that may allow for negative expiratory transpulmonary pressures. Methods: Ten Yorkshire pigs were instrumented and mechanically ventilated using transpulmonary pressure measurements. Baseline lung mechanics were obtained for the following parameters: Vt=10mL/kg, PEEP=5cmH2O, and FiO2 = 0. 21. Lungs were injured by instilling 5% Tween-20 (3ml/kg), and ARDS was established when PF ratios fell <200. After a single recruitment maneuver (40 cmH2O x 40sec.), the animals were randomized into a PtpPEEP Group with PEEP adjusted to maintain the end-expiratory transpulmonary pressure?0 cmH2O, or the Control Group where PEEP was adjusted based on the lower PEEP scale as per ARDSNet guidelines. Cardiovascular and respiratory parameters were recorded hourly for 24hr. Results: After 12hr, the PtpPEEP Group started separating from the Control Group, maintaining, as per protocol, PtpPEEP pressures?0 cmH2O, while the Control Group showed negative values 48% of time. Overall, the PtpPEEP Group had an odds ratio of 4.3 for normal oxygenation (PF ratio>300), and intrapulmonary shunting significantly lower than the Control Group (p<0.01). Regression analysis showed that shunt fractions increased with time (p<0.01) associated with decreasing PF ratios (<0.01); however, for the same PF ratios, the PtpPEEP Group showed lower shunt fractions than the Control (p<0.01). Conclusions: In our study, the extent of shunting was a consequence of the PEEP optimization strategy. The PtpPEEP Group improved the oxygenation and shunt fractions, indicating that maintaining a PtpPEEP?0 cmH2O may have a significant impact on ventilation/perfusion matching.

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Introduction: The purpose of this study is to evaluate the potential for using transthoracic echocardiography (TTE) as an alternative modality to assist in placement of venovenous double lumen bicaval catheters via the internal jugular (IJ) approach. Hypothesis: Currently TTE or fluoroscopy are used to assist in placement of VV ECMO cannulae. The hypothesis of this study is there is no increased complication rate using bedside TTE performed by trained critical care specialists for this procedure. Methods: This is a retrospective cohort of adult patients admitted with refractory respiratory failure at two tertiary hospitals of the Montefiore Medical Center, Bronx, New York. The inclusion criterion was patients placed on VV ECMO using TTE to assist in placement of the cannula. Venous cannulation was achieved with the aid of ultrasound guidance of the right IJ vein. The Avalon Elite® Dual Lumen Bicaval catheter was placed by a cardiothoracic surgeon. The guidewire was identified at the IVC/right atrial junction via transthoracic echococardiographic views obtained by an intensivist. The proper ECMO cannula position was confirmed at the level of the tricuspid valve via a transthoracic echocardiographic view with the aid of color Doppler flow. A chest radiograph was obtained to rule out pneumothorax post cannula insertion. Results: Between June 1, 2009 and August 20, 2012, there were 5 cases of VV ECMO via the right IJ approach performed at the bedside assisted by TTE performed by trained intensivists. The median (IQR) age was 27 (23, 44) years, 57% were men and 57% were African American. The median (IQR) body mass index was 25 (23, 32). Two patients had ARDS, two had status asthmaticus and one had pulmonary edema. The mean+/-SD PF ratio was 48+/-8 in the ARDS group and 67 in the patient with pulmonary edema. The pCO2 was 113 and 148 in the group with status asthmaticus. The median (IQR) hospital length of stay was 12(9,54) days. All patients survived with no complications related to catheter placement or while on ECMO. The crude 90-day mortality was zero (n=4, one patient has not reached 90-days). Conclusions: TTE performed by an intensivist presents a viable option to aid in VV ECMO cannulation.

Anaerobic Threshold Assessment Through the Ventilatory Method During Roller-Ski Skating Testing: Right or Wrong?

This study aimed at questioning the validity of the ventilatory method to determine the anaerobic threshold (respiratory compensation point [RCP]) during an incremental roller-ski skating test to exhaustion. Nine elite crosscountry skiers were evaluated. The skiers carried out an incremental roller-ski test on a treadmill with the V2 skating technique. Ventilatory parameters were continuously collected breath by breath, thanks to a portable gas exchange measurement system. Poling signal was obtained using instrumented ski poles. For each stage, ventilatory and poling signals were synchronized and averaged. The poor coefficient of interobserver reliability for the time at RCP confirmed the great difficulty felt by the 3 blinded reviewers for the RCP determination. Moreover, the reviewer agreed with the impossibility of determining RCP in 4 of the 9 skiers. There was no significant difference between breathing frequency (Bf) and poling frequency (Pf) during the last 8 stages. However, it seems that the differences observed during the first stages arose from the use of either a strictly 1:1 or a 1:2 Bf to Pf ratio when the exercise intensity was still moderate. So, even if there were significant differences between the frequencies, the Bf was strictly subordinate to the Pf during the entire test. In the same way, the normalized tidal volume and peak poling forces curves were superposable. These findings showed that when the upper body is mainly involved in the propulsion, the determinants of the ventilation are strictly dependent on the poling pattern during an incremental test to exhaustion. Thus, during roller-ski skating, the determination of RCP must be used cautiously because too much depending on mechanical factors.

The Addition of a Membrane Oxygenator to a Ventricular Assist Device in a Patient with Acute Respiratory Distress Syndrome

A 12-year-old boy with Marfan’s syndrome required a biventricular assist device (VAD) after an aortic root replacement. The patient developed acute respiratory distress syndrome and required escalating ventilator support. We hypothesized that the addition of a membrane oxygenator in series with the assist device would improve gas exchange and allow for a more lung-protective ventilator approach. A membrane oxygenator was placed in series with the right VAD resulting in a blood path of right atrium to VAD to oxygenator to pulmonary artery. Circuit function was gauged by monitoring flow and oxygenator pressures and periodic circuit inspections and oxygenator blood gases. Heparin was titrated to maintain unfractionated antifactor Xa levels of .3–.7 IU/mL and partial thromboplastin time of 60–80 seconds. The initial sweep gas supplying the oxygenator was 5 L/min at an FIO2 of 1.0, which achieved a pH &gt;7.40 and a PF ratio &gt;250. The pre- and post-oxygenator pressures were 55–60 mmHg and 45–50 mmHg, respectively, and the measured flow at the oxygenator outlet was 2.0–2.2 L/min. The patient was changed from high-frequency oscillatory ventilation to pressure-controlled synchronized intermittent ventilation with pH maintained at 7.35–7.40 and PF ratio &gt;250. Paralytics were discontinued and the patient’s neurologic condition was deemed intact. The patient hemorrhaged after a sternal closure and required transfusions and antifibrinolytics that led to thrombus in the membrane and membrane circuitry, which were replaced without incident. The patient’s respiratory status remained stable; however, his overall condition worsened as a result of additional organ dysfunction and septicemia, and he did not survive. The addition of a membrane oxygenator to a VAD is feasible and supplements gas exchange permitting the use of more lung protective ventilation.

Obesity is Associated with Reduced Brain Tissue Oxygen Tension After Severe Brain Injury

BackgroundObesity has been associated with compromised tissue oxygenation and reduced organ perfusion. The brain is critically dependent on oxygen delivery, and reduced brain tissue oxygen tension (PbtO2) may result in poor outcome after brain injury. We tested the hypothesis that obesity is associated with compromised PbtO2 after severe brain injury.MethodsPatients with severe brain injury (GCS score ≤ 8) who underwent continuous PbtO2 monitoring were retrospectively identified from a prospective single-center database. Patients, were classified by body mass index (BMI = weight (kg)/m2) and were included if they were obese (BMI ≥ 30) or non-obese (BMI = <30).ResultsSixty-nine patients (mean age 46.4 ± 17.0 years) were included. Mean daily PbtO2 was 25.8 (9.6) mmHg for the 28 obese and 31.8 (12.3) mmHg for the 41 non-obese patients (P = 0.03). Initial PbtO2 and mean daily maximum PbtO2 measurements also were significantly lower in obese patients than in non-obese patients. Univariate predictors of compromised PbtO2 (defined as minutes PbtO2 < 20 mmHg) included elevated BMI (P = 0.02), presence of ARDS (P < 0.01), mean PaO2 (P < 0.01), maximum FiO2 (P < 0.01), mean PaO2:FiO2 (P < 0.01), and mean CVP (P < 0.01). In multivariable analysis, BMI was significantly associated with compromised PbtO2 (P = 0.02). Sex, age, and mean CVP were also identified as significant predictors of compromised PbtO2; ARDS and PF ratio were not.ConclusionsIn patients with severe brain injury, obesity was found to be an independent predictor of compromised PbtO2. This effect may be mediated through obesity-related pulmonary dysfunction and inadequate compensatory mechanisms.

A comparison between the Boussignac™ continuous positive airway pressure mask and the venturi mask in terms of improvement in the PaO2/F i O2 ratio in morbidly obese patients undergoing bariatric surgery: a randomized controlled trial

This study compared the Boussignac™ continuous positive airway pressure (CPAP) mask with the venturi face mask in terms of the postoperative PaO2/F(I)O2 (PF) ratio in morbidly obese patients after bariatric surgery. Following hospital Research Ethics Board approval and written informed consent, morbidly obese (body mass index > 35 kg·m(-2)) patients undergoing bariatric surgery were recruited. The patients were anesthetized and laparoscopic Roux-en-Y gastric bypass was performed. Patients were assigned randomly to receive either the Boussignac (Boussignac Group) or the venturi face mask (Venturi Group) immediately after tracheal extubation. Patients were transported to the postanesthesia care unit, and the respective devices were applied for one hour. The PF ratio was recorded after tracheal intubation and at one hour and two hours post extubation. The percent forced expiratory volume (%FEV1) and the percent forced vital capacity (%FVC) were recorded preoperatively and at one hour and two hours post extubation. Independent Student's t tests were used for continuous variables, and the Chi square test was used for categorical variables. P < 0.05 was considered statistically significant. Eighty-one patients (Group Boussignac, n = 43; Group Venturi, n = 38) completed the study. Mean ages and body mass indices were similar in the two groups. At one hour post extubation, the PF ratio in the Boussignac Group was 361 (170) compared with 279 (91) in the Venturi Group (P = 0.007), and at two hours post extubation, the PF ratio in the Boussignac Group was 371 (162) compared with 323 (127) in the Venturi Group (P = 0.1). The postoperative %FEV(1) and %FVC were comparable in both groups at all time points. Compared with the venturi mask, the Boussignac CPAP mask improves the postoperative PF ratio in morbidly obese patients after bariatric surgery. The postoperative %FEV1 and %FVC are comparable for both groups.

Effects of Neutrophil Elastase Inhibitor on Progression of Acute Lung Injury After Liver Transplantation

We read with interest the article recently published in Transplantation by Uchida et al. (1) describing protective function of neutrophil elastase (NE) inhibitor in liver ischemia-reperfusion injury. The authors concluded that NE inhibition may represent an effective therapeutic option in liver transplantation (LT). Despite recent advances in surgical techniques and perioperative management, LT has a relatively high in-hospital mortality and morbidity rate (2). In addition to ischemia-reperfusion injury, pulmonary complications including acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) frequently occur after LT. If uncontrolled, ALI/ARDS leads to in-hospital death. Therefore, prevention of postoperative ALI/ARDS is important to reduce in- hospital mortality after LT. Pulmonary endothelial barrier disruption plays a critical role in the development of ALI/ARDS. Especially, neutrophils and NE play important roles in endothelial injury and increased vascular permeability, which are the characteristics of ALI/ARDS (3). Pulmonary vascular hyperpermeability, a cause of hypoxemia during the early postoperative course, could be caused by NE released from neutrophils accumulating in the lung (4). Sivelestat (ONO Pharmacol, Osaka, Japan) is a synthetic selective inhibitor of NE (5). In the field of organ transplantation, there have been some reports showing beneficial effects of Sivelestat in lung or liver ischemia-reperfusion injury in experimental animal model (1, 6, 7). However, there has been no clinical study examining its usefulness in LT. In this study, we therefore conducted a prospective, nonrandomized, clinical pilot study to examine the effect of Sivelestat on postoperative ALI in patients undergoing LT. Between April 2007 and May 2008, 62 consecutive adult patients who underwent living donor LT at Kyoto University Hospital were prospectively enrolled in the study. After matching for underlying disease, the patients were nonrandomly assigned to receive a continuous intravenous infusion of 300 mg/kg per day of Sivelestat (Sivelestat group, n=31) dissolved in 50 mL of saline or saline only (control group, n=31) just after admission to the intensive care unit after surgery. The patients in both the groups were treated until the ratio of arterial oxygen tension (PaO2)-to-the fractional concentration of inspired oxygen (FiO2) (PF ratio) was more than 300. Blood samples for arterial blood gas analysis were drawn twice daily throughout the experiment. The duration of systemic inflammatory response syndrome (SIRS) was also measured. The definition for SIRS was in accordance with that of the American College of Chest Physicians/ Society of Critical Care Medicine Consensus Conference (8). The protocol was approved by the ethical committee of Kyoto University Hospital following the guidelines of the 1975 Declaration of Helsinki. The written informed consent was obtained from each patient before participation in the study. Continuous variables were expressed as the means±SD, or as the median and range, and the differences in continuous variables were analyzed by Student's t test. Comparisons of the categorical or ordinal variables were performed using chi-square test or Fisher exact test where appropriate. A P value less than 0.05 was considered significant. The characteristics of patients including age, gender, underlying disease, Child-Pugh classification, and model for end-stage liver disease score, were not different between the two groups. The decrease in the PF ratio after surgery shown in the control group was prevented in the Sivelestat group (Fig. 1). The PF ratios on the first, second, and third postoperative days (PODs) in the Sivelestat group were significantly higher than those in the control group (POD1, 322±74 vs. 258±90, P=0.002; POD2, 318±106 vs. 224±88, P=0.002; and POD3, 330±91 vs. 214±82, P<0.001), whereas the PF ratio on intensive care unit admission was lower in the Sivelestat group than that in the control group (324±87 vs. 359±90, P=0.160). Moreover, the duration of SIRS was significantly shorter in the Sivelestat group compared with that in the control group (2.3±2.1 days vs. 3.7±3.7 days, P=0.023).FIGURE 1.: The ratio of arterial oxygen tension to the fractional concentration of inspired oxygen (PF ratio) after surgery. The decrease in PF ratio after surgery shown in the control group was prevented in the Sivelestat group. ICU, intensive care unit; POD, postoperative day.This is the first report that shows the preventive effect of Sivelestat against ALI after living donor LT in clinical settings. Several studies suggested that Sivelestat improved ALI partially by inhibiting inflammation or nuclear factor-κB activity (6, 9, 10). Although plasma levels of proinflammatory and antiinflammatory cytokines were not examined in this study, the amelioration of posttransplant ALI might be partially caused by its antiinflammatory effect. Further investigations are thus required to elucidate mechanism of the preventive effect of Sivelestat against ALI. Randomized controlled trials of Sivelestat for posttransplant ALI after LT are needed to confirm this finding. Toshimi Kaido Shinji Uemoto Division of Hepato-Biliary-Pancreatic and Transplant Surgery Department of Surgery Graduate School of Medicine Kyoto University Kyoto, Japan

A Hemogram of Clarias batrachus Parasitized by Two Species of Hemoflagellates (Trypanosoma batrachi Qadri, 1962 and Trypanoplasma haematalis n.sp.) as an Indicator of Infectivity

The blood of a freshwater catfish, Clarias batrachus Linn. was scanned for hemoflagellate infectivity by examination of fresh blood (hanging drop preparations and hematocrit) and stained smears. Trypanosoma batrachiQadri, 1962 occurring at a prevalence of 29.5% (intensity: 4 to 20 forms/20 min scan) is reported as a new locality record (Bareilly, Uttar Pradesh, India). A new species of monomorphic biflagellate was also found in 8.1% of the infected fish concurrently with Trypanosoma. Based on its morpho-cytostatistical features, flagellar length, and AF:PF ratio, the new species is named Trypanoplasma haematalis n.sp. A few selected hematological parameters (Hb%, ESR, PCV, and MCH) of infected fish were estimated to ascertain the validity as an indicator of flagellate infection under natural and experimentally-induced conditions, by inoculation of 3 ml of infected blood in laboratory-reared, healthy uninfected fish. In either case, the blood parameters recorded significant changes up to a maximum of 55.79% (Hb%, Group B3), 151.04% (ESR, Group B3), 65.45% (PCV, Group B3), and 106.26% (MCH, Group B3) suggesting that hemograms of fishes may be utilized as indicators of some infestation, which offers scope to corroborate it with flagellate infectivity.

Comparison of the Pulse Oximetric Saturation/Fraction of Inspired Oxygen Ratio and the Pa o 2 /Fraction of Inspired Oxygen Ratio in Children

Although diagnostic criteria for acute lung injury (ALI) and ARDS are clear, invasive arterial sampling is required for computation of Pao(2)/fraction of inspired oxygen (Fio(2)) [PF] ratios. The pulse oximetric saturation (Spo(2))/Fio(2) (SF) ratio may be a reliable noninvasive alternative to the PF ratio for identifying children with lung injury. We electronically queried blood gas measurements from two tertiary care pediatric ICUs (PICUs). Included in the analysis were corresponding measurements of Spo(2), Pao(2), and Fio(2) charted within 15 min of each other when Spo(2) values were between 80% and 97%. Computed PF and SF ratios were compared to identify threshold values for SF ratios that correspond to PF criteria for ALI (< or = 300) and ARDS (< or = 200). Data from one PICU were used for derivation and validated with measurements from the second PICU. From the 1,298 observations in the derivation data set, SF ratio could be predicted by the regression equation SF = 76 + 0.62 x PF (p < 0.0001, R(2) = 0.61). SF ratios of 263 and 201 corresponded to PF ratios of 300 and 200, respectively. The ALI SF cutoff of 263 had 93% sensitivity and 43% specificity, and the ARDS cutoff of 201 had 84% sensitivity and 78% specificity. Applying these values to the 1,845 observations in the validation data set yielded a sensitivity of 86% and specificity of 47% for ALI and a sensitivity of 68% and specificity of 84% for ARDS. SF ratio is a reliable noninvasive marker for PF ratio to identify children with ALI or ARDS.

Changes in Functional Residual Capacity During Weaning from Mechanical Ventilation: A Pilot Study

Reduction of high positive end-expiratory pressure levels and pressure support ventilation (PSV) are frequently used before tracheal extubation in critically ill patients, but the impact of PSV on functional residual capacity (FRC) is unknown. In this study, we sought to detect the changes of FRC and pulmonary function during a weaning protocol in patients ventilated after cardiac surgery. The LUFU system (Dräger Medical, Lübeck, Germany) estimates FRC by oxygen washout, a variant of multiple breath nitrogen washout, using a sidestream O(2) analyzer. Postoperative cardiac surgery patients were initially ventilated using biphasic positive airway pressure ventilation (BiPAP) with a positive end-expiratory pressure of 10 mbar. The upper pressure limit was adjusted to deliver a tidal volume of 6-8 mL/kg (BIPAP 10). After 30 min, the upper and lower pressure limits were both reduced by 3 mbar (BIPAP 7). When spontaneous breathing efforts were detected, ventilation mode was switched to continuous positive airway pressure (CPAP) with PSV using the former lower pressure limit as the CPAP level and the corresponding pressure support of the former BIPAP adjustment (CPAP 7_1). Measurements were repeated after 30 min (CPAP 7_2). Ten patients were studied. FRC decreased (BIPAP 10: 3.6 [1.0] L; BIPAP 7: 3.1 [0.9] L; CPAP 7_1: 2.9 [0.9] L; CPAP 7_2: 2.7 [0.6] L [Mean (SD)]; MANOVA: P = 0.017), as did PF ratio (BIPAP 10: 420 [114] mm Hg; BIPAP 7: 405 [110] mm Hg; CPAP 7_1: 353 [70] mm Hg; CPAP 7_2: 340 [70] mm Hg [Mean (SD)]; MANOVA: P = 0.045). PaCO(2) did not change significantly over time (P = 0.221). Decreasing FRC during the weaning process after cardiac surgery may, at least in part, be explained by alveolar derecruitment. Whether this variable could help guide a weaning protocol has to be studied further.

Direct Hemoperfusion With a β2‐Microglobulin‐selective Adsorbent Column Eliminates Inflammatory Cytokines and Improves Pulmonary Oxygenation

Acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) are characterized by a high mortality rate; therefore, ARDS/ALI in humans is a leading cause of morbidity and mortality in critically ill patients. As previously reported, cytokines play a critical role as signaling molecules that initiate, amplify, and perpetuate inflammatory responses on a local and systemic basis, and the polymyxin-B immobilized direct hemoperfusion system (PMX-DHP) is effective for the treatment of ARDS/ALI. Furthermore, another direct hemoperfusion system using the beta2-microglobulin-selective adsorbent column, Lixelle, the direct hemoperfusion treatment (Lixelle-DHP), has been applied in some cases to patients who are affected with systemic inflammatory response syndrome. The aim of this study is to evaluate the therapeutic efficacy of Lixelle-DHP in the treatment of ARDS/ALI. Four patients, aged 67-79 years old (mean 72 +/- 6.2 years), diagnosed with ARDS/ALI were treated with Lixelle-DHP. The P(a)O(2)/fraction of inspired oxygen (F(i)O(2)) ratio (PF ratio) was 90.0 +/- 22.9 before the treatment, and it increased to 129.9 +/- 5.6 at 72 h afterward the start of treatment. Inflammatory cytokines such as interleukin (IL)-1 beta, IL-6, soluble intercellular adhesion molecule 1 (sICAM-1) decreased significantly after the treatment. All patients were still alive after one month. However, while IL-2 had decreased significantly after the treatment, it had returned by the next treatment. It is possible that Lixelle-DHP might be able to improve the PF ratio and mortality rate as a result of decreased cytokines, and it has been suggested that Lixelle-DHP has a beneficial influence in the treatment of ARDS/ALI.

The role of lung function in brain tissue oxygenation following traumatic brain injury

Previous studies have demonstrated that periods of low brain tissue oxygen tension (PbtO2) are associated with poor outcome after head trauma but have primarily focused on cerebral and hemodynamic factors as causes of low PbtO2. The purpose of this study was to investigate the influence of lung function on PbtO2 with an oxygen challenge (increase in fraction of inspired oxygen [FiO2] concentration to 1.0). This prospective observational cohort study was performed in the neurointensive care unit of the Level 1 trauma center at San Francisco General Hospital. Thirty-seven patients with severe traumatic brain injury (TBI) undergoing brain tissue oxygen monitoring as part of regular care underwent an oxygen challenge, consisting of an increase in FiO2 concentration from baseline to 1.0 for 20 minutes. Partial pressure of arterial oxygen (PaO2), PbtO2, and the ratio of PaO2 to FiO2 (the PF ratio) were determined before and after oxygen challenge. Patients with higher PF ratios achieved greater PbtO2 during oxygen challenge than those with a low PF ratio because they achieved a higher PaO2 after an oxygen challenge. Lung function, specifically the PF ratio, is a major determinant of the maximal PbtO2 attained during an oxygen challenge. Given that patients with TBI are at risk for pulmonary complications such as pneumonia, severe atelectasis, and adult respiratory distress syndrome, lung function must be considered when interpreting brain tissue oxygenation.

Growth Promotion of a Sea Water Algae with Sterile, Ulva pertusa Kjellman, Due to Supplemental Lighting

Ulva pertusa is widely used as human food and also to feed cultured fish. U. pertusa is expected to be used as a bio-filter for purification of breeding - circulation water in the terrestrial aquaculture of fish. Insufficient sunshine and lower temperature causes bad commercial production. In order to realize stable cultivation of U. pertusa throughout the year, experiments on the growth of a sea water algae with sterile, U. pertusa Kjellman, due to supplemental lighting were performed. An illuminance of 1×104 lx in the treatment areas and 2×104 lx in the control, when the illuminance was 8×104 lx in the greenhouse. Artificial lighting was added during the daytime in treatments 1∼3. The mounting height of each luminaire was adjusted to have a PPFD of 140 μmol m-2s-1. Each lamp had the R/FR PF ratio of 3.8, 1.2, 0.8. Considering of relationship between the growth and cumulative PPFD including daylight and supplemental lighting, the growth of the experimental area were superior to the control area. U. pertusa can be grown with warm sea water using supplemental lighting. But under the growth environment with daylight and supplemental lighting together, it is difficult to recognize whether the R/FR PF ratio influences photomorphogenesis.

Effects of PMX‐DHP Treatment for Patients With Directly Induced Acute Respiratory Distress Syndrome

Endotoxin-removal direct hemoperfusion column containing polymyxin B immobilized fibers (PMX-DHP) is an effective procedure for the treatment of sepsis-induced acute respiratory distress syndrome (ARDS). We investigated retrospectively the effects and appropriate timing of PMX-DHP induction for directly induced ARDS in 38 patients. PMX-DHP was carried out twice for two hours. Blood pressure, heart rate (HR) and PaO(2)/FIO(2) (PF) ratio, leukocytes, platelets, endotoxin, inflammatory cytokines and clusters of differentiated peripheral neutrophils and monocytes were measured before and after PMX-DHP. Acute Physiology and Chronic Health Evaluation (APACHE) II scores, Sequential Organ Failure Assessment (SOFA) scores and lung injury scores (LIS) were determined at the time of starting PMX-DHP. The underlying causes of ARDS were pneumonia in 29 patients and aspiration pneumonia in 9 patients. The patients were divided into Survivors (n = 21) and Nonsurvivors (n = 17). Mortality was 45% at 30 days after PMX-DHP. The APACHE II and SOFA scores and the LIS were not significantly different between the two groups. The time from the onset of ARDS to the start of PMX-DHP was significantly delayed between the two groups. PMX-DHP significantly improved the PF ratio, HR and systolic blood pressure in the Survivors compared to the Nonsurvivors. The function of active monocytes in the peripheral blood was significantly suppressed after PMX-DHP. This early induction of PMX-DHP is indicated for directly induced ARDS. In the Nonsurvivors, this delay could have led to undesirable responses to oxygenation and circulation after PMX-DHP.