Effects of different recruitment maneuvers on bacterial translocation and ventilator- induced lung injury.

BACKGROUND: Investigated in the present study were the effects of various recruitment maneuvers (RMs) using the same inflation pressure-time product on bacterial translocation from lung to blood, and ventilator-induced lung injury (VILI). METHODS: Tracheotomy was performed on anesthetized rats, and ventilation was initiated using pressure-controlled mode. Subsequently, Pseudomonas aeruginosa was inoculated through the tracheotomy tube and ventilated for 30 minutes before rats were randomly separated into 4 groups. Group 1 underwent sustained inflation (SI), Group 2 underwent low-pressure SI, Group 3 underwent modified sigh, and Group 4 was a control group. Blood cultures were taken at baseline, 15 minutes after randomization (after each RM for the first hour), and finally at 75 minutes after the last RM. The rats were euthanized and the lungs were extirpated. The left lung was taken for measurement of wet:dry weight ratio, and the right lung was used for pathologic evaluation. RESULTS: Positive blood cultures were found to be higher in Group 3 at early study periods. Total pathological scores were also higher in Group 3. CONCLUSION: Higher severity of ventilator-induced lung injury occurred in the modified sigh group, evidenced by bacterial translocation and results of histopathological evaluation.

The effects of airway pressure and inspiratory time on bacterial translocation.

BACKGROUND: Mechanical ventilation with high peak inspiratory pressure (PIP) induces lung injury and bacterial translocation from the lung into the systemic circulation. We investigated the effects of increased inspiratory time on translocation of intratracheally inoculated bacteria during mechanical ventilation with and without extrinsic positive end-expiratory pressure (PEEP). METHODS: Rats were ventilated in pressure-controlled mode with 14 cm H2O PIP, 0 cm H2O PEEP, I:E ratio 1/2, and Fio2 1.0. Subsequently, 0.5 mL of 10(5) cfu/mL Pseudomonas aeruginosa was inoculated through tracheostomy and rats were randomly assigned to six groups; two low-pressure groups (LP)1/2, 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and LP2/1 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two high-pressure groups (HP)1/2, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and HP2/1, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two HP PEEP groups (HPP)1/2, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 1/2, and HPP2/1, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 2/1. Blood cultures were obtained every 30 min. The rats were killed and their lungs were processed. RESULTS: When compared with baseline values, Pao2 decreased in the LP1/2, LP2/1, HP1/2, and HP2/1 groups at the last time point, but the decline in Pao2 reached statistical significance in only the HP1/2 group. The bacterial translocation rate was greater in group HPP2/1 than group HPP1/2 (P = 0.01). CONCLUSIONS: We found that high PIP, with or without prolonged inspiratory time, increased the rate of bacterial dissemination. PEEP prevented bacterial translocation in the high PIP group. However, the protective effect of PEEP was lost when inspiratory time was prolonged.

[Neurogenic pulmonary edema: a prospective study based on observation]. / Nörojenik pulmoner ödem: Gözleme dayali prospektif bir çalisma.

BACKGROUND: In this study, we evaluated the cause and the clinical course of neurogenic pulmonary edema which has developed abruptly in some of the patients in the neurosurgical intensive care unit. METHODS: We evaluated 223 patients in the neurosurgical ICU (116 males; 107 females; mean age 44.4+/-19.5). Five of these had worsening in neurological evaluation and oxygenation and were diagnosed as having a neurogenic pulmonary edema. Patients with pneumonia were excluded from the study. RESULTS: We identified acute hydrocephaly in three patients and re-bleeding of an aneurysm in one as the cause of neurogenic pulmonary edema. No cause could be identified in the remaining patient. Although four patients could be discharged from the ICU, one died due to multiorgan failure. CONCLUSION: Physicians should be careful about neurogenic pulmonary edema, a life-threatening clinical condition, that develops within hours of a neurologic event and usually resolves with neurologic recovery.

Bleomycin induces alveolar epithelial cell death through JNK-dependent activation of the mitochondrial death pathway.

Exposure to bleomycin in rodents induces lung injury and fibrosis. Alveolar epithelial cell death has been hypothesized as an initiating mechanism underlying bleomycin-induced lung injury and fibrosis. In the present study we evaluated the contribution of mitochondrial and receptor-meditated death pathways in bleomycin-induced death of mouse alveolar epithelial cells (MLE-12 cells) and primary rat alveolar type II cells. Control MLE-12 cells and primary rat alveolar type II cells died after 48 h of exposure to bleomycin. Both MLE-12 cells and rat alveolar type II cells overexpressing Bcl-X(L) did not undergo cell death in response to bleomycin. Dominant negative Fas-associating protein with a death domain failed to prevent bleomycin-induced cell death in MLE-12 cells. Caspase-8 inhibitor CrmA did not prevent bleomycin-induced cell death in primary rat alveolar type II cells. Furthermore, fibroblast cells deficient in Bax and Bak, but not Bid, were resistant to bleomycin-induced cell death. To determine whether the stress kinase JNK was an upstream regulator of Bax activation, MLE-12 cells were exposed to bleomycin in the presence of an adenovirus encoding a dominant negative JNK. Bleomycin-induced Bax activation was prevented by the expression of a dominant negative JNK in MLE-12 cells. Dominant negative JNK prevented cell death in MLE-12 cells and in primary rat alveolar type II cells exposed to bleomycin. These data indicate that bleomycin induces cell death through a JNK-dependent mitochondrial death pathway in alveolar epithelial cells.

Effects of body temperature on ventilator-induced lung injury.

PURPOSE: To evaluate the effects of body temperature on ventilator-induced lung injury. MATERIAL AND METHODS: Thirty-four male Sprague-Dawley rats were randomized into 6 groups based on their body temperature (normothermia, 37 +/- 1 degrees C; hypothermia, 31 +/- 1 degrees C; hyperthermia, 41 +/- 1 degrees C). Ventilator-induced lung injury was achieved by ventilating for 1 hour with pressure-controlled ventilation mode set at peak inspiratory pressure (PIP) of 30 cmH2O (high pressure, or HP) and positive end-expiratory pressure (PEEP) of 0 cmH2O. In control subjects, PIP was set at 14 cmH2O (low pressure, or LP) and PEEP set at 0 cmH2O. Systemic chemokine and cytokine (tumor necrosis factor alpha , interleukin 1 beta , interleukin 6, and monocyte chemoattractant protein 1) levels were measured. The lungs were assessed for histological changes. RESULTS: Serum chemokines and cytokines were significantly elevated in the hyperthermia HP group compared with all 3 groups, LP (control), normothermia HP, and hypothermia HP. Oxygenation was better but not statistically significant in hypothermia HP compared with other HP groups. Cumulative mean histology scores were higher in hyperthermia HP and normothermia HP groups compared with control and normothermia HP groups. CONCLUSIONS: Concomitant hyperthermia increased systemic inflammatory response during HP ventilation. Although hypothermia decreased local inflammation in the lung, it did not completely attenuate systemic inflammatory response associated with HP ventilation.

Time required for equilibration of arterial oxygen pressure after setting optimal positive end-expiratory pressure in acute respiratory distress syndrome.

OBJECTIVE: To evaluate the time course of Pao2 change following the setting of optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome (ARDS). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit of a university hospital. PATIENTS: Twenty-five consecutive patients with ARDS. INTERVENTIONS: ARDS was diagnosed during pressure-regulated volume control ventilation with tidal volume of 7 mL/kg actual body weight, respiratory rate of 12 breaths/min, inspiratory/expiratory ratio of 1:2, Fio2 of 1, and PEEP of 5 cm H2O. A critical care attending physician obtained pressure volume curves and determined the lower inflection point. Following a rest period of 30 mins with initial ventilation variables, PEEP was set at 2 cm H2O above the lower inflection point, and serial blood samples were collected during 1-hr ventilation with optimal PEEP. Arterial blood gas analyses were performed at 1, 3, 5, 7, 9, 11, 15, 20, 30, 45, and 60 mins. MEASUREMENTS AND MAIN RESULTS: Twenty-five patients were found eligible for the study. Three patients were excluded due to deterioration of oxygen saturation and hemodynamic instability following the initiation of optimal PEEP. Eight cases (36%) were considered to be of pulmonary origin and 14 cases (64%) of extrapulmonary origin. Optimal PEEP levels were 14 +/- 3 cm H2O and 14 +/- 4 cm H2O in pulmonary and extrapulmonary ARDS, respectively. Pao2 demonstrated a 130 +/- 101% increase at the end of 1-hr period in total study population. This improvement did not differ significantly between pulmonary and extrapulmonary forms of ARDS (135 +/- 118% vs. 127 +/- 95%, p = .8). Mean 90% oxygenation time was found to be 20 +/- 19 mins. In the subset of patients with ARDS of pulmonary origin, 90% oxygenation time was 25 +/- 26 mins, whereas it was 17 +/- 15 mins in patients with ARDS of extrapulmonary origin (p = .8). CONCLUSIONS: Our data showed that 20 mins would be adequate for obtaining a blood gas sample in ARDS patients with pulmonary and extrapulmonary origin after application of optimal PEEP 2 cm H2O above the lower inflection point.

Reactive oxygen species are required for hyperoxia-induced Bax activation and cell death in alveolar epithelial cells.

Exposure of animals to hyperoxia results in respiratory failure and death within 72 h. Histologic evaluation of the lungs of these animals demonstrates epithelial apoptosis and necrosis. Although the generation of reactive oxygen species (ROS) is widely thought to be responsible for the cell death observed following exposure to hyperoxia, it is not clear whether they act upstream of activation of the cell death pathway or whether they are generated as a result of mitochondrial membrane permeabilization and caspase activation. We hypothesized that the generation of ROS was required for hyperoxia-induced cell death upstream of Bax activation. In primary rat alveolar epithelial cells, we found that exposure to hyperoxia resulted in the generation of ROS that was completely prevented by the administration of the combined superoxide dismutase/catalase mimetic EUK-134 (Eukarion, Inc., Bedford, MA). Exposure to hyperoxia resulted in the activation of Bax at the mitochondrial membrane, cytochrome c release, and cell death. The administration of EUK-134 prevented Bax activation, cytochrome c release, and cell death. In a mouse lung epithelial cell line (MLE-12), the overexpression of Bcl-XL protected cells against hyperoxia by preventing the activation of Bax at the mitochondrial membrane. We conclude that exposure to hyperoxia results in Bax activation at the mitochondrial membrane and subsequent cytochrome c release. Bax activation at the mitochondrial membrane requires the generation of ROS and can be prevented by the overexpression of Bcl-XL.

[Iatrogenic hypernatremia during hydatid cyst operation]. / Karaciger Kist Hidatik Operasyonunda Iyatrojenik Hipernatremi.

Hypernatremia due to salt gain is generally iatrogenic. This case report presents a 55 year-old woman who was operated because of hepatic hydatid cyst. At the end of the operation, following extubation the patient was unconscious and serum sodium concentration was found to be 185 mEq/ L. The patient was entubated again and transferred to the intensive care unit. When the patient awaked and became conscious at 36th hour in intensive care unit, she was extubated and transferred to ward with serum sodium concentration of 142 mEq/L. The serum sodium concentration should be monitored carefully in hydatid cyst operation, during which hypertonic saline is used for scelosidal effects as general anesthesia can mask neurologic signs due to hypernatremia.

Effects of sustained inflation and postinflation positive end-expiratory pressure in acute respiratory distress syndrome: focusing on pulmonary and extrapulmonary forms.

OBJECTIVE: To investigate whether the response to sustained inflation and postinflation positive end-expiratory pressure varies between acute respiratory distress syndrome with pulmonary (ARDS(exp)) and extrapulmonary origin (ARDS(exp)). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: A total of 11 patients with ARDS and 13 patients with ARDS. INTERVENTIONS: A 7 ml/kg tidal volume, 12-15 breaths/min respiratory rate, and an inspiratory/expiratory ratio of 1:2 was used during baseline ventilation. Positive end-expiratory pressure levels were set according to the decision of the primary physician. Sustained inflation was performed by 45 cm H2O continuous positive airway pressure for 30 secs. Postinflation positive end-expiratory pressure was titrated decrementally, starting from a level of 20 cm H2O to keep the peripheral oxygen saturation between 92% and 95%. Fio2 was decreased, and baseline tidal volume, respiratory rate, inspiratory/expiratory ratio were maintained unchanged throughout the study period. MEASUREMENTS AND MAIN RESULTS: Blood gas, airway pressure, and hemodynamic measurements were performed at the following time points: at baseline and at 15 mins, 1 hr, 4 hrs, and 6 hrs after sustained inflation. After sustained inflation, the Pao2/Fio2 ratio improved in all of the patients both in ARDS(p) and ARDS(exp). However, the Pao2/Fio2 ratio increased to >200 in four ARDS(p) patients (36%) and in seven ARDS(p) patients (54%). In two of those ARDS patients, the Pao2/Fio2 ratio was found to be <200, whereas none of the ARDS(p) patients revealed Pao2/Fio2 ratios of <200 at the 6-hr measurement. Postinflation positive end-expiratory pressure levels were set at 16.7 +/- 2.3 cm H O in ARDS(p) and 15.6 +/- 2.5 cm H2O in ARDS. The change in Pao /Fio ratios was found statistically significant in patients with ARDS(p) (p =.0001) and with ARDS(p) (p =.008). Respiratory system compliance increased in ARDS patients (p =.02), whereas the change in ARDS was not statistically significant. CONCLUSIONS: Sustained inflation followed by high levels of postinflation positive end-expiratory pressure provided an increase in respiratory system compliance in ARDS; however, arterial oxygenation improved in both ARDS forms.

Comparison of efficacy of intraarticular application of tenoxicam, bupivacaine and tenoxicam: bupivacaine combination in arthroscopic knee surgery.

Arthroscopic knee surgery is one of the most common surgeries done in outpatient settings; however, postoperative pain is believed to be the major barrier for discharge and early rehabilitation. In this study we evaluated and compared the efficacy of intraarticular application of long-lasting non-steroidal analgesic drug tenoxicam, a long-lasting local anaesthetic bupivacaine and combination of the two on postoperative pain after arthroscopic knee surgery. With the approval of the local ethics committee and signed informed consent of the patients, 75 American Society of Anesthesiologists I-II patients aged between 18 and 65 years going under elective arthroscopic meniscectomy were included in this randomized, blind, prospective study. The patients were divided into three groups: group-T (GT) patients ( n=25) had intraarticular 20 mg of tenoxicam in 20 ml normal saline; group-B (GB) patients ( n=25) had 50 mg bupivacaine in 20 ml normal saline (0.25%); group-BT (GBT) patients ( n=25) had intraarticular 20 mg of tenoxicam and 50 mg bupivacaine (0.25%) in 20 ml normal saline after completion of the surgery and before deflation of the tourniquet. Postoperative analgesia was maintained by intravenous tramadol hydrochloride 50 mg/s at the first 4 h and paracetamol 500 mg and codeine 7.5 mg preparation (Pacofen) as needed (maximum six per day) during the study period. The numeric rating scale (NRS) values were at rest and at active-passive motion at 4, 12, 24 and 48 h, total analgesic consumption, at 4 h for tramadol and at the end of 48 h for oral medication; and patient satisfaction at the end of 48 h was evaluated and recorded. The demographic features of the patients, and tourniquet times, were found to be similar between the groups. Group BT had significantly lower NRS values than GB at 12 h at rest. Group BT was found to have significantly lower NRS values at 4 h compared with GT, and significantly lower NRS values at 12 h compared with GB. Group BT was found to have significantly lower NRS values at 48 h compared with GB. Group T had significantly higher NRS values at 4 h compared with GB. Group B had significantly higher values at 12 h compared with GT and GBT. Group B used significantly more analgesics than GBT and GT throughout the study period. Group BT patients had significantly more satisfaction at the end of the study period when compared with GT and GB. Application of intraarticular tenoxicam-bupivacaine solution is a simple, safe and effective method of analgesia after arthroscopic meniscectomy with high patient satisfaction.

Recruitment maneuver: does it promote bacterial translocation?

OBJECTIVE: High peak airway opening pressures (Pao) are used routinely during recruitment maneuvers to open collapsed lung units. High peak Pao, however, can cause lung injury as evidenced by translocation of intratracheally inoculated bacteria. In this study we explored whether recruitment maneuvers that used high Pao could cause translocation of the intratracheally inoculated from the alveoli into the systemic circulation. DESIGN: Prospective, randomized, animal study. SETTING: Experimental animal care laboratory. SUBJECTS: Eighteen male Sprague Dawley rats. INTERVENTIONS Rats were anesthetized, tracheostomized, and ventilated with 14 cm H2O peak Pao and 0 cm H2O positive end-expiratory pressure (PEEP) in pressure-controlled ventilation (frequency, 30 bpm; inspiratory/expiratory ratio, 1:2; Fio, 1). Intratracheal inoculation of 500 microL of saline containing 1 x 10 colony forming units/mL was performed before randomization into three groups (n = 6 in each): a low-pressure group (14 cm H2O peak Pao, 0 cm H2O PEEP), a high-pressure group (45 cm H2O peak Pao, 0 cm H2O PEEP), and a recruitment maneuver group (14 cm H2O peak Pao, 0 cm H2O PEEP, and a recruitment maneuver sustained inflation of 45 cm H2O continuous positive airway pressure for 30 secs every 15 mins). Blood samples for blood gas analysis were obtained before intratracheal instillation of bacteria and at the end of the experimental protocol (2 hrs). Blood cultures were obtained before and after bacterial instillation at 30-min intervals during the experiment. Blood samples were cultured directly in sheep blood, MacConkey, and Iso-Sensitest agars and were observed on the second day. Bacteremia was defined as the presence of one or more colonies of in 1 mL of blood. MEASUREMENTS AND MAIN RESULTS: The blood cultures were positive for in only six rats in the high-pressure group and remained negative throughout the study period in the low-pressure and recruitment maneuver groups. Oxygenation deteriorated in all groups after intratracheal instillation of bacteria. In the high-pressure group, oxygenation decreased from 417 +/- 67 mm Hg to 79 +/- 20 mm Hg ( p=.004), whereas in the low-pressure and recruitment maneuver groups PaO2 decreased from 410 +/- 98 mm Hg and 383 +/- 78 mm Hg to 287 +/- 105 mm Hg ( p=.031) and 249 +/- 59 mm Hg (p =.11), respectively. CONCLUSION: Intermittent recruitment maneuvers applied as a sustained inflation superimposed on low-pressure ventilation with 0 cm H2O PEEP did not cause translocation of intratracheally inoculated.

The effects of IgM-enriched immunoglobulin preparations in patients with severe sepsis [ISRCTN28863830].

INTRODUCTION: In this prospective, randomized controlled study, we aimed to evaluate the effect of IgM-enriched immunoglobulin treatment on progression of organ failure and septic shock in patients with severe sepsis. MATERIALS AND METHODS: Forty-two patients with severe sepsis were enrolled in the study. Patients in the study group (n = 21) received an intravenous immunoglobulin preparation (Pentaglobin in addition to standard therapy. Pentaglobin therapy was commenced on the day of diagnosis of severe sepsis: 5 ml/kg per day Pentaglobin (38 g/l IgG, 6 g/l IgM, and 6 g/l IgA) was infused over 6 hours and repeated for 3 consecutive days. Patients in the control group (n = 18) received standard sepsis therapy, but no immunoglobulin administration. Blood samples for procalcitonin (PCT) measurements were taken daily for 8 days. Severity of critical illness and development of organ failure were assessed by obtaining daily acute physiological and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores. RESULTS AND DISCUSSION: Procalcitonin levels showed a statistically significant decrease in the Pentaglobin group (P < 0.001); however, an improvement in SOFA scores could not be demonstrated. Procalcitonin levels and SOFA scores did not change significantly in the control group. Septic shock incidence (38% versus 57%) and 28-day mortality rate (23.8% versus 33.3%) were found to be similar between the Pentaglobin and control groups. The evaluation of serial APACHE II scores did not demonstrate a difference between Pentaglobin and control groups either. CONCLUSION: Present data could not demonstrate any beneficial effects of polyclonal immunoglobulin preparation Pentaglobin on organ morbidity, septic shock incidence and mortality rate in patients with severe sepsis.

[Is jejunal feeding efficient in critically ill patients?]. / Kritik hastada jejunal beslenme etkin midir?

BACKGROUND: The aim of this study is to compare the results of jejunal and gastric nutrition in the ICU. METHODS: Caloric intake and nutritional complications were recorded for ten days period in patients receiving gastric (n = 21) and jejunal (n = 22) feeding. RESULTS: Caloric requirements were reached on the 3rd day of nutrition in 86% of jejunal and 28% of gastric feeding patients (p 0.001). In jejunal group, delivered calorie/goal calorie ratio was found 15-20% higher than the gastric group. Serum albumin, triglyceride, cholesterol levels and nitrogen balance did not show significant differences between groups. Vomiting (p 0.01) and colouring of tracheal aspirates (p 0.05) were more frequent in gastric group, however positive tracheal culture frequency did not differ between the groups. CONCLUSION: It is concluded that higher caloric intakes could be tolerated earlier in patients receiving jejunal feeding.