Increase In PaO2 Research Articles

Effect of changes in ionized calcium concentration in arterial blood and metabolic acidosis on the arterial partial pressure of oxygen in dogs

To evaluate the effects of metabolic acidosis and changes in ionized calcium (Ca2+) concentration on PaO2 in dogs. 33 anesthetized dogs receiving assisted ventilation. Normal acid-base status was maintained in 8 dogs (group I), and metabolic acidosis was induced in 25 dogs. For 60 minutes, normocalcemia was maintained in group I and 10 other dogs (group II), and 10 dogs were allowed to become hypercalcemic (group III); hypocalcemia was then induced in groups I and II. Groups II and IV (5 dogs) were treated identically except that, at 90 minutes, the latter underwent parathyroidectomy. At intervals, variables including PaO2, Ca2+ concentration, arterial blood pH (pHa), and systolic blood pressure were assessed. In group II, PaO2 increased from baseline value (96 +/- 2 mm Hg) within 10 minutes (pHa, 7.33 +/- 0.001); at 60 minutes (pHa, 7.21 +/- 0.02), PaO2 was 108 +/- 2 mm Hg. For the same pHa decrease, the PaO2 increase was less in group III. In group I, hypocalcemia caused PaO2 to progressively increase (from 95 +/- 2 mm Hg to 104 +/- 3 mm Hg), which correlated (r = -0.66) significantly with a decrease in systolic blood pressure (from 156 +/- 9 mm Hg to 118 +/- 10 mm Hg). Parathyroidectomy did not alter PaO2 values. Induction of hypocalcemia and metabolic acidosis each increased PaO2 in anesthetized dogs, whereas acidosis-induced hypercalcemia attenuated that increase. In anesthetized dogs, development of metabolic acidosis or hypocalcemia is likely to affect ventilatory control.

Efficacy and Safety of Levofloxacin Treatment of Community—Acquired Pneumonia in Hospitalized Patients

The aim of this prospective study was to determine the efficacy and safety of levofloxacin in the treatment of community-aquired pneumonia (CAP) in outpatient with ineffective antibiotic management, requiring hospitalization. The examined group included 25 patients (11 M, 14 F) of mean age 70 ± 17.5 years with abnormalities in X-ray on admission to hospital. Risk factors for pneumonia and previous antibacterial therapy were analyzed. In the hospital they were treated for 7 days with levofloxacin 500 mg twice a day administred intravenously. Body temperature, blood cell count, ESR, CRP, AST, ALT, LDH, CPK, creatine, urea, potassium, sodium, ABG, and ECG were measured on admission and in the 3-rd and 7- th day of therapy. The chest X-rays were performed and analyzed on hospital discharge. 18 patients were aged > 65 yrs, cardiovascular diseases co-existed in 14, COPD in 9, smoking habit in 12, renal failure in 3, diabetes in 3 and alkohol addiction in 1 cases. On admission 4 patients had respiratory failure, 10 hypoxaemia. During therapy a decrease of body temperature (p < 0.001), concentration of CRP (p < 0.004) and LDH (p < 0.03), CPK (p < 0.04) and increase of PaO2 (p < 0.012) were observed. The changes of other parameters were not statistically significant. We did not observe any changes in ECG. On discharge from the hospital in 16 patients complete regression and in 6 patients partial regression of lesions in chest X-ray examination were observed. In 3 patients levofloxacin therapy was noneffective: in 2 because of persistent high body temperature after 3 days of treatment and in 1 patients because of recurrent of fever. Adverse events were mild. Transient exacerbation of renal failure was observed in 3 patients. Our study demonstrates that levofloxacine ni dose 2 × 500 mg given intravenously for 7 days is effective and safe in treatment of CAP in patients with previously ineffective antibacterial therapy.

Comment on Point:Counterpoint “In health and in a normoxic environment, V̇o2 maxis/is not limited primarily by cardiac output and locomotor muscle blood flow”

Comment on Point:Counterpoint “In health and in a normoxic environment, V̇<scp>o</scp>_{2 max}is/is not limited primarily by cardiac output and locomotor muscle blood flow”

Effects of an alveolar recruitment maneuver on cardiovascular and respiratory parameters during total intravenous anesthesia in ponies

To evaluate pulmonary and cardiovascular effects of a recruitment maneuver (RM) combined with positive end-expiratory pressure (PEEP) during total intravenous anesthesia in ponies. 6 healthy adult Shetland ponies. After premedication with detomidine (10 microg/kg, IV), anesthesia was induced with climazolam (0.06 mg/kg, IV) and ketamine (2.2 mg/kg, IV) and maintained with a constant rate infusion of detomidine (0.024 mg/kg/h), climazolam (0.036 mg/kg/h), and ketamine (2.4 mg/kg/h). The RM was preceded by an incremental PEEP titration and followed by a decremental PEEP titration, both at a constant airway pressure difference (deltaP) of 20 cm H2O. The RM consisted of a stepwise increase in deltaP by 25, 30, and 35 cm H2O obtained by increasing peak inspiratory pressure (PIP) to 45, 50, and 55 cm H2O, while maintaining PEEP at 20 cm H2O. Hemodynamic and pulmonary variables were analyzed at every step of the PEEP titration-RM. During the PEEP titration-RM, there was a significant increase in PaO 2 (+12%), dynamic compliance (+ 62%), and heart rate (+17%) and a decrease in shunt (-19%) and mean arterial blood pressure (-21%) was recorded. Cardiac output remained stable. Although baseline oxygenation was high, Pa(O2) and dynamic compliance further increased during the RM. Despite the use of high PIP and PEEP and a high tidal volume, limited cardiovascular compromise was detected. A PEEP titration-RM may be used to improve oxygenation in anesthetized ponies. During stable hemodynamic conditions, PEEP titration-RM can be performed with acceptable adverse cardiovascular effects.

Effects of Antenatal Glucocorticoids on Circulatory Adaptation at Birth in the Ovine Fetus

Objective: Adaptation to extra-uterine life requires dramatic increase in pulmonary blood flow. Mechanisms that induce pulmonary vasodilatation at birth are incompletely understood but include alveolar ventilation, increase in PaO₂, and production of vasoactive mediators. We hypothesized that antenatal glucocorticoids (GC) increase pulmonary vasodilatation to birth-related stimuli. Study Design: To test this hypothesis, we studied the pulmonary hemodynamic response at birth to mechanical ventilation with low (<10%) and then with high (100%) FiO₂ in chronically prepared late-gestation fetal lambs treated or not by antenatal maternal steroids. Results: Basal mean aortic and pulmonary artery pressure (PAP), left pulmonary blood flow, pulmonary vascular resistance (PVR), and blood gas were similar between control and dexamethasone-treated animals (GC group). During mechanical ventilation with low FiO₂, mean PVR decreased by 40% in the control group (from 0.44 ± 0.01 to 0.25 ± 0.01 mm Hg/ml/min) and by 60% in the GC group (from 0.44 ± 0.02 to 0.19 ± 0.02 mm Hg/ml/min) (p < 0.01). When subsequently ventilated with 100% O₂, there was no difference in PVR decrease between groups (0.15 ± 0.02 mm Hg/ml/min in the GC group vs. 0.14 ± 0.01 mm Hg/ml/min in the control group). Conclusion: Antenatal GC enhance pulmonary vasodilatation induced by alveolar ventilation at birth but do not alter the pulmonary vascular response to O₂. We speculate that antenatal steroids exposure improve adaptation at birth through acceleration of both parenchymal and vascular lung maturation.

Intrapulmonary percussive ventilation in acute exacerbations of COPD patients with mild respiratory acidosis: a randomized controlled trial [ISRCTN17802078

IntroductionWe hypothesized that the use of intrapulmonary percussive ventilation (IPV), a technique designed to improve mucus clearance, could prove effective in avoiding further deterioration in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) with mild respiratory acidosis.MethodsThe study was performed in a medical intensive care unit of a university hospital. Thirty-three patients with exacerbations of COPD with a respiratory frequency ≥ 25/min, a PaCO2 > 45 Torr and 7.35 ≤ pH ≤ 7.38 were included in the study. Patients were randomly assigned to receive either standard treatment (control group) or standard treatment plus IPV (IPV group). The IPV group underwent two daily sessions of 30 minutes performed by a chest physiotherapist through a full face mask. The therapy was considered successful when both worsening of the exacerbation and a decrease in pH to under 7.35, which would have required non-invasive ventilation, were avoided.ResultsThirty minutes of IPV led to a significant decrease in respiratory rate, an increase in PaO2 and a decrease in PaCO2 (p < 0.05). Exacerbation worsened in 6 out of 17 patients in the control group versus 0 out of 16 in the IPV group (p < 0.05). The hospital stay was significantly shorter in the IPV group than in the control group (6.8 ± 1.0 vs. 7.9 ± 1.3 days, p < 0.05).ConclusionIPV is a safe technique and may prevent further deterioration in patients with acute exacerbations of COPD with mild respiratory acidosis.

Intercomparison of recruitment maneuver efficacy in three models of acute lung injury*

To compare the relative efficacy of three forms of recruitment maneuvers in diverse models of acute lung injury characterized by differing pathoanatomy. We compared three recruiting maneuver (RM) techniques at three levels of post-RM positive end-expiratory pressure in three distinct porcine models of acute lung injury: oleic acid injury; injury induced purely by the mechanical stress of high-tidal airway pressures; and pneumococcal pneumonia. Laboratory in a clinical research facility. Twenty-eight anesthetized mixed-breed pigs (23.8 +/- 2.6 kg). The RM techniques tested were sustained inflation, extended sigh or incremental positive end-expiratory pressure, and pressure-controlled ventilation. Oxygenation and end-expiratory lung volume. The post-RM positive end-expiratory pressure level was the major determinant of post-maneuver PaO2, independent of the RM technique. The pressure-controlled ventilation RM caused a lasting increase of PaO2 in the ventilator-induced lung injury model, but in oleic acid injury and pneumococcal pneumonia, there were no sustained oxygenation differences for any RM technique (sustained inflation, incremental positive end-expiratory pressure, or pressure-controlled ventilation) that differed from raising positive end-expiratory pressure without RM. Recruitment by pressure-controlled ventilation is equivalent or superior to sustained inflation, with the same peak pressure in all tested models of acute lung injury, despite its lower mean airway pressure and reduced risk for hemodynamic compromise. Although RM may improve PaO2 in certain injury settings when traditional tidal volumes are used, sustained improvement depends on the post-RM positive end-expiratory pressure value.

Positive end-expiratory pressure applied to the dependent lung during one-lung ventilation improves oxygenation and respiratory mechanics in patients with high FEV1

The aim of this study was to test the efficacy of positive end-expiratory pressure (PEEP) to the dependent lung during one-lung ventilation, taking into consideration underlying lung function in order to select responders to PEEP. Forty-six patients undergoing open-chest thoracic surgical procedures were studied in an operating room of a university hospital. Patients were randomized to receive zero end-expiratory pressure (ZEEP) or 10 cmH2O of PEEP to the dependent lung during one-lung ventilation in lateral decubitus. The patients were stratified according to preoperative forced expiratory volume in 1 s (FEV1) as an indicator of lung function (below or above 72%). Oxygenation was measured in the supine position, in the lateral decubitus with an open chest, and after 20 min of ZEEP or PEEP. The respiratory system pressure-volume curve of the dependent hemithorax was measured in supine and open-chest lateral decubitus positions with a super-syringe. Application of 10 cmH2O of PEEP resulted in a significant increase in PaO2 (P < 0.05). This did not occur in ZEEP group, considered as a time matched control. PEEP improved oxygenation only in patients with high FEV1 (from 11.6+/-4.8 to 15.3+/-7.1 kPa, P < 0.05). There was no significant change in the low FEV1 group. Dependent hemithorax compliance decreased in lateral decubitus, more in patients with high FEV1 (P < 0.05). PEEP improved compliance to a greater extent in patients with high FEV1 (from 33.6+/-3.6 to 48.4+/-3.9 mLcmH2O(-1), P < 0.05). During one-lung ventilation in lateral decubitus, PEEP applied to the dependent lung significantly improves oxygenation and respiratory mechanics in patients with rather normal lungs as assessed by high FEV1.

Inhalation of the Endothelin-A Receptor Antagonist LU-135252 at Various Doses in Experimental Acute Lung Injury

We studied the effects of the inhaled endothelin-A receptor antagonist LU-135252 at different doses on hemodynamics and gas exchange in an animal model of acute lung injury. Thirtysix piglets (27 +/- 1 kg) were anesthetized, mechanically ventilated (FiO2 1.0), and surfactant-depleted by repeated lung lavage. The animals were randomly assigned to receive either nebulized LU- 135252 for 30 minutes at a dose of 0.3 mg/kg (n = 12), or at a dose of 3.0 mg/kg (n = 12); n = 12 animals received no further treatment (Controls). Induction of acute lung injury decreased PaO2 from 566 +/- 8 mmHg to 53 +/- 2 mmHg (mean +/- SEM) and increased intrapulmonary shunt (QS/QT) from 13 +/- 1% to 57 +/- 2%. Inhalation of LU-135252 at either dose induced a significant and sustained increase in PaO2 (0.3 mg/kg: 349 +/- 39 mmHg; 3.0 mg/kg: 219 +/- 40 mmHg), and a significant decrease in QS/QT (0.3 mg/kg: 19 +/- 2%; 3.0 mg/kg: 27 +/- 3%) when compared with Controls (PaO2: 50 +/- 3 mmHg, QS/QT: 50 +/- 5%) (P < 0.05; values at 4 hours). Mean pulmonary artery pressure in LU-135252-treated animals (0.3 mg/kg: 31 +/- 2 mmHg; 3.0 mg/kg: 30 +/- 1 mmHg) was significantly lower than in Controls (40 +/- 2 mmHg), while there were no differences in mean arterial pressure and cardiac output. We conclude that inhalation of LU-135252 at either dose improved gas exchange and hemodynamics comparably, indicating that the lower dose was already sufficient to block the majority of endothelin-A receptors in ventilated regions of the injured lung.

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

Maldistribution of exogenous surfactant may preclude any clinical response in acute lung injury associated with surfactant dysfunction. Our previous studies have shown the effectiveness of surfactant lavage after homogenous lung injury. The present study utilizes a histologically confirmed non-homogeneous lung injury model induced by saline lung-lavage followed by meconium injected into a mainstem bronchus. Piglets were then treated with Infasurf or Exosurf by lavage (I-LAVAGE, n = 7; E-LAVAGE, n = 5) or bolus (I-BOLUS, n = 8; E-BOLUS, n = 5), or went untreated (CONTROL, n = 4). Lavage administration utilized a dilute surfactant (35 ml/kg; 4 mg phospholipid/ml) instilled into the lung, followed by gravity drainage. The retained doses of the respective surfactant in the lavage and bolus groups were similar. Results showed that the surfactant distribution was more uniform in the lavage groups compared to the bolus groups. Significant and consistent increases in PaO2 were observed in the lavage groups compared to the bolus groups and the controls. PaO2 (mmHg) at 240 min posttreatment: I-LAVAGE = 297 +/- 54, E-LAVAGE = 280 +/- 57; I-BOLUS = 139 +/- 31; E-BOLUS = 152 +/- 29; C = 119 +/- 73 (mean +/- SEM). Other improved pulmonary function parameters favored lavage administration. We conclude that better surfactant distribution achieved by lavage administration can be more effective than bolus administration in this type of non-homogeneous lung injury.

Intravenous arginine vasopressin in critically ill children: is it beneficial?

Arginine-vasopressin (AVP) may be more effective than epinephrine in shock states and as an end-of-life salvage maneuver. However, there is only limited experience using AVP in children. Our study aim was to evaluate the effect of AVP administration on hemodynamic and ventilatory parameters in critically ill children. Eight critically ill children (1 month to 12 years old) were treated with AVP during the years 2000-2001. Two patients had had head trauma, and six had surgical correction of congenital heart disease. All patients suffered severe septic or cardiogenic shock with a low cardiac output state and were considered to be near death. AVP was administered continuously at a dose of 0.0003-0.002 U/kg/min. Hemodynamic and ventilatory parameters and vasopressor doses were compared before and after AVP initiation. One patient survived with a good neurologic outcome. Seven patients succumbed while receiving AVP. Systolic and diastolic blood pressure increased significantly (P < 0.03) following AVP initiation. The epinephrine requirement decreased from 2.3 to 1.7 microg/kg/min. Blood gases improved with a significant (P < 0.05) increase of PaO2. Oxygenation index and PaO2/FiO2 ratio improved significantly, and ventilatory support requirements and positive inspiratory pressure (PIP) decreased significantly. Despite a significant improvement in hemodynamic and ventilatory support parameters, survival to hospital discharge was not achieved when AVP was used in critically ill pediatric patients. We hypothesize that earlier administration of AVP may be more beneficial.

11 Optical Imaging of The Neonatal Brain

Background: Perinatal brain injury remains an important problem for critically ill newborn infants. Optical methods provide a means of monitoring brain oxygenation safely in an intensive care environment. Information on light absorption and scattering throughout the brain can be obtained by measuring the time of flight of photons from multiple sources and detectors. The aim of this study was to reconstruct three dimensional images of regional cerebral oxygenation from newborn infants using a time resolved optical imaging system.Methods: Ten infants were studied with a median (range) postmenstrual age of 30 (26–37) weeks. The median age at study was 28 (3–40) days. Three infants had evidence of unilateral intraventricular haemorrhage (IVH) on cranial ultrasound examination. One infant had suffered an acute hypoxic-ischaemic injury following uterine rupture and was studied whilst receiving ventilatory support. Optical data were collected using a custom built 32 channel optical imaging system. Static data sets were acquired from each infant; in addition, data from the ventilated infant were acquired following induced changes in PaO2 and PaCO2. Three dimensional images of tissue absorption were reconstructed and were then converted into maps of regional [Hb], and [HbO2].Results: Movement artifact and poor optode contact limited the ability to obtain a complete data set from 5 of the infants. Images were reconstructed from the remaining five, including the infant who had suffered the hypoxic-ischaemic insult. Dynamic images of volume change and oxygenation change were obtained from this infant following changes in the PaCO2 and PaO2 respectively. A large increase in [Hb] and [HbO2], corresponding to an increase in cerebral blood volume, was seen following an increase in PaCO2. An increase in [HbO2] was seen following an increase in PaO2. Of the remaining 4 infants for whom images were reconstructed, 2 had evidence of unilateral IVH; these infants were found to have increased absorption of light on the side of the haemorrhage, corresponding to an increase in [Hb] and decrease in [HbO2] in that region.Conclusion: Using a time resolved optical imaging system we have obtained novel information on regional cerebral blood volume and oxygenation and been able to assess regional oxygenation in the presence of a unilateral IVH. These images demonstrate the feasibility of this technique and the potential to provide unique information on regional cerebral oxygenation in the developing brain.

Impact of interpleural analgesia on respiratory function after transthoracic spine surgery: 301.

Local anaesthesia produced lowerpain scores vs. tramadol (p<0, 05), with 72% of patients in the catheter group requiring no tramadol in the following hour and first 3 days. A general increase in the PaO2 was observed (81% preoperatively vs. 94% postoperatively), correlating with haemoglobin and haematocrit was observed. No statistically signifficant difference was observed in the incidence of postoperative nausea and vomiting.

Utilizing the peritoneum for gas exchange with oxygenated perfluorocarbons

Introduction: This pilot study attempted to determine if it was possible to deliver a clinically significant amount of oxygen to a large animal, with induced hypoxia, by perfusing the abdomen with oxygenated perfluorocarbons. Methods: 15 pigs weighing 45 to 55 kg were rendered hypoxic by ventilating them with a blend of nitrogen and oxygen to achieve sub-atmospheric inspired oxygen concentrations (FiO2) ranging from 18–10%, resulting in baseline arterial oxygen pressures (PaO2) of 65.9 ± 9.7 mmHg to 26.6 ± 2.8 mmHg, respectively. Peritoneal perfusion was then performed in 8 animals with oxygenated perfluorocarbon and 7 with oxygenated saline. This study was approved by the IACUC. Results: The average increase in PaO2 with oxygenated perfluorocarbon perfusion ranged from 8.1 to 18.2 mmHg. A common treatment effect of 12.8 mmHg (95% CI = 7.4 to 18.2; p-value < 0.001) was estimated across all FiO2 values, representing the average mean difference in oxygen uptake between PFC and saline when oxygenation was on, irrespective of the level of FiO2. The most clinically relevant results occurred at a FiO2 of 14%, resulting in a baseline PaO2 of 39.4 ± 5.0 mmHg, but increasing to 55.3 ± 7.6 mmHg with oxygenated perfluorocarbon perfusion. Control experiments with oxygenated saline did not demonstrate any significant gas exchange effects. Conclusions: The peritoneal cavity can be used for gas exchange and, in our model, yielded clinically relevant quantities of supplemental oxygen. This technique may have potential for supportive care of patients dying from hypoxia in the setting of a reversible lung injury.

PERITONEAL PERFUSION WITH OXYGENATED PERFLUOROCAR-BONS CAN INCREASE ARTERIAL OXYGENATION IN A PORCINE MODEL

Objective: Despite maximal mechanical ventilatory support, patients die from hypoxia in the setting of potentially reversible pulmonary failure. This pilot study attempted to determine if a clinically significant amount of oxygen could be delivered, in the setting of hypoxia, by perfusing the abdomen with oxygenated perfluorocarbons (PFC). Methods: 15 pigs, 45 to 55 kg, were ventilated with inspired oxygen concentrations (FIO2) ranging from 10–18%, resulting in baseline arterial oxygen pressures (PaO2) of 26.6± 2.8 mmHg to 65.9± 9.7 mm Hg, respectively. Peritoneal perfusion was then performed with oxygenated PFC (n=8) or oxygenated saline (n=7). Results: Perfusion with oxygenated PFC resulted in an increase in PaO2, ranging from 8.1–18.2 mmHg. A common treatment effect can be estimated across all FiO2 values, representing the average mean difference in oxygen uptake between PFC and saline when oxygenation was on, irrespective of level of FiO2 (12.8 mmHg; 95% CI=7.4 to 18.2; p<0.0001; Fig.1). Oxygenated saline did not demonstrate any significant gas exchange. Conclusion: In our model, the peritoneal cavity can be used as an artificial lung to provide clinically relevant quantities of supplemental oxygen. This technique may have a supportive role for hypoxic patients with reversible lung injury.Figure 1: Observed mean of oxygen uptake, by treatment group and oxygenation condition. PFC, oxygenation on (observed: filled squares; fitted solid line); saline oxygenation on (observed: filled circles; fitted dashed line

Continuous tracheal gas insufflation during partial liquid ventilation in juvenile rabbits with acute lung injury

To examine the hypothesis that combined treatment with tracheal gas insufflation (TGI) and partial liquid ventilation (PLV) may improve pulmonary outcome relative to either treatment alone in acute lung injury (ALI), saline lavage lung injury was induced in 24 anesthetized, ventilated juvenile rabbits that were then randomly assigned to receive (n = 6/group) 1) conventional mechanical ventilation (CMV) alone, 2) continuous TGI at 0.5 l/min, 3) PLV with perfluorochemical liquid, and 4) combined TGI and PLV (TGI + PLV), and subsequently ventilated with minimized pressures and tidal volume (Vt) to keep arterial Po(2) (Pa(O(2))) >100 Torr and arterial Pco(2) (Pa(CO(2))) at 45-60 Torr for 4 h. Gas exchange, lung mechanics, myeloperoxidase, IL-8, and histomorphometry [including expansion index (EI)] were assessed. The CMV group showed no improvement in lung mechanics and gas exchange; all treated groups had significant increases in compliance, Pa(O(2)), ventilation efficacy index (VEI), and EI, and decreases in PaCO(2), oxygenation index, physiological dead space-to-Vt ratio (Vd/Vt), myeloperoxidase, and IL-8, relative to the CMV group. TGI resulted in lower peak inspiratory pressure, Vt, Vd/Vt, and greater VEI vs. PLV group; PLV resulted in greater compliance, Pa(O(2)), and EI vs. TGI. TGI + PLV resulted in decreased peak inspiratory pressure, Vt, Vd/Vt, and increased VEI compared with TGI, improved compliance and EI compared with PLV, and a further increase in Pa(O(2)) and oxygenation index and a decrease in PaCO(2) vs. either treatment alone. These results indicate that combined treatment of TGI and PLV results in improved pulmonary outcome than either treatment alone in this animal model of ALI.

Effects of therapeutic hypercapnia on mesenteric ischemia-reperfusion injury.

Hypercapnic acidosis protects against direct lung injury in in vivo and ex vivo models, however, lung injury/acute respiratory distress syndrome commonly occurs after a nonpulmonary etiology. We investigated whether therapeutic hypercapnia (TH)-deliberate elevation of carbon dioxide (CO2) tension-would protect against lung injury after splanchnic ischemia-reperfusion injury in an in vivo model. TH was associated with preservation of lung mechanics, attenuation of protein leakage, and improved oxygenation compared with control conditions. Lung protection was therapeutic as well as prophylactic. Protection was dose-dependent, but inspired CO2 concentrations above 5.0% were associated with little additional lung protection. Before lung injury, increasing FICO2 resulted in a dose-dependent increase in PaO2. Lung protection with hypercapnia occurred despite pulmonary artery pressures that were greater than observed with normocapnia. Reperfusion increased lipid peroxidation (tissue 8-isoprostane concentration) in the bowel, liver, and lung, and caused histologically apparent bowel injury; however, none of these effects was altered by TH. Therefore, TH-induced by adding CO2 to inspired gas-provides consistent protection against lung injury in terms of lung permeability, oxygenation, and lung mechanics after mesenteric ischemia-reperfusion. These data further support the emerging evidence for ongoing physiologic study of TH at the bedside.

Hypercapnia increases cerebral tissue oxygen tension in anesthetized rats.

To test the hypotheses that deliberate elevation of PaCO(2) increases cerebral tissue oxygen tension (PBrO(2)) by augmenting PaO(2) and regional cerebral blood flow (rCBF). Anesthetized rats were exposed to increasing levels of inspired oxygen (O(2)) or carbon dioxide (CO(2); 5%, 10% and 15%, n = 6). Mean arterial blood pressure (MAP), PBrO(2) and rCBF were measured continuously. Blood gas analysis and hemoglobin concentrations were determined for each change in inspired gas concentration. Data are presented as mean +/- standard deviation with P < 0.05 taken to be significant. The PBrO(2) increased in proportion to arterial oxygenation (PaO(2)) when the percentage of inspired O(2) was increased. Proportional increases in PaCO(2) (48.7 +/- 4.9, 72.3 +/- 6.0 and 95.3 +/- 15.4 mmHg), PaO(2) (172.2 +/- 33.1, 191.7 +/- 42.5 and 216.0 +/- 41.8 mmHg), and PBrO(2) (29.1 +/- 9.2, 49.4 +/- 19.5 and 60.5 +/- 23.0 mmHg) were observed when inspired CO(2) concentrations were increased from 0% to 5%, 10% and 15%, respectively, while arterial pH decreased (P < 0.05 for each). Exposure to CO(2) increased rCBF from 1.04 +/- 0.67 to a peak value of 1.49 +/- 0.45 (P < 0.05). Following removal of exogenous CO(2), arterial blood gas values returned to baseline while rCBF and PBrO(2) remained elevated for over 30 min. The hypercapnia induced increase in PBrO(2) was threefold higher than that resulting from a comparable increase in PaO(2) achieved by increasing the inspired O(2) concentration (34.9 +/- 14.5 vs 11.4 +/- 5.0 mmHg, P < 0.05). These data support the hypothesis that the combined effect of increased CBF, PaO(2) and reduced pH collectively contribute to augmenting cerebral PBrO(2) during hypercapnia.

Cardiopulmonary effects of nebulized sodium nitroprusside in term infants with hypoxic respiratory failure

ObjectiveTo study whether nebulized nitroprusside (neb-NP) improves oxygenation in term infants with hypoxic respiratory failure (HRF). Study designWe studied 22 newborn term infants (gestational age, 39.7±0.4 weeks [mean±SEM]; birth weight, 3.6±0.1 kg) with hypoxia (Pao2<100 mm Hg) during mechanical ventilation (Fio2=1.0). Sodium nitroprusside (5 mg followed by 25 mg) was nebulized into the inspiratory arm of the ventilator circuit. Vital signs and arterial blood gas values were recorded after 20 minutes at each dose and before and after initiation of inhaled nitric oxide (iNO). ResultsPao2 increased significantly with 5 mg neb-NP (from 64.6±5.6 to 90.1±15.3 mm Hg, P=.04) and with 25 mg neb-NP (113.2±20.4 mm Hg, P=.009). Differences between mean Pao2 at 5 mg versus 25 mg neb-NP were also statistically significant (P=.03). When comparing the effect of neb-NP to iNO, the treatment-induced increases in Pao2 were similar (52.1±18.7 vs 62.2±18.2 mm Hg, respectively, P=not significant). ConclusionsNeb-NP causes a dose-dependent increase in oxygenation in term infants with HRF, similar in magnitude to iNO. Neb-NP may be beneficial in infants with HRF when iNO is not readily available.

Anti-cholinergic bronchodilators versus beta2-sympathomimetic agents for acute exacerbations of chronic obstructive pulmonary disease.

Inhaled bronchodilators form the mainstay of treatment for acute exacerbations of COPD. Two types of agent are used routinely, either singly or in combination: anticholinergic agents and beta2-sympathomimetic agonists. To assess the effect of anti-cholinergic agents on lung function and dyspnea in patients with acute exacerbations of COPD, compared with placebo or short-acting beta-2 agonists. A comprehensive search of the literature was carried out on MEDLINE, EMBASE, CINAHL and the Cochrane COPD Trials Register, using the terms: bronchodilator* OR ipratropium OR oxitropium. References listed in each included trial were searched for additional trial reports. Studies were included if the participants were adult patients with a known diagnosis of COPD and had symptoms consistent with criteria for acute exacerbation of COPD. All randomized controlled trials that compared inhaled ipratropium bromide or oxitropium bromide to appropriate controls were considered. Appropriate control treatments included placebo, other bronchodilating agents, or combination therapies. Studies of acute asthma or ventilated patients were excluded. All trials that appeared to be relevant were assessed by two reviewers who independently selected trials for inclusion. Differences were resolved by consensus. Four trials compared the short-term effects of ipratropium bromide vs. a beta2-agonist. Short-term changes in FEV1 (up to 90 minutes) showed no significant difference between beta2-agonist and ipratropium bromide treated patients. The differences were similar among the studies and when combined: Weighted Mean Difference (WMD) 0.0 liters (95% Confidence Interval (95% CI) -0.19, 0.19). There was no significant additional increase in change in FEV1 on adding ipratropium to beta2-agonist: WMD 0.02 liter (95% CI -0.08, 0.12). Long-term effects (24 hours) of the ipratropium bromide and beta2-agonist treatment combination were similar: WMD 0.05 liters (95%CI -0.14, 0.05). Neither of two studies found significant changes in PaO2, either short- or long-term, with ipratropium vs. beta-agonist, although one showed an increase in PaO2 in subjects receiving ipratropium bromide at 60 minutes. Adverse drug reactions included dry mouth and tremor. There was no evidence that the degree of bronchodilation achieved with ipratropium bromide was greater than that using a short-acting beta2-agonist. The combination of a beta2-agonist and ipratropium did not appear to increase the effect on FEV1 more than either used alone.