Effect of continuous positive airway pressure helmet on respiratory function following surgical procedures in brachycephalic dogs: A randomized controlled trial.

OBJECTIVE: To evaluate the effect of continuous positive airway pressure (CPAP) on respiratory function in the early postoperative period of brachycephalic dogs. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 32 dogs. METHODS: Dogs were assigned to recover with or without CPAP (control) and assessed at specific time points over 1 h. Treatment was discontinued for dogs with a CPAP tolerance score of 3 or more (from a range of 0-4). The primary outcome was pulse oximetry (SpO2). Secondary outcomes were arterial O2 pressure (PaO2)/FiO2 ratio (PaO2/FiO2), arterial CO2 pressure (PaCO2), and rectal temperature. For dogs that reached a CPAP tolerance score of 3 or more, only the data collected up to the time point before discontinuation were included in the analysis. The treatment effect (ß) was analyzed using random effects models and the results were reported with 95% confidence intervals. RESULTS: Dogs were assigned randomly to each protocol. Baseline characteristics in both groups were comparable. Arterial blood gases were obtained in seven control group dogs and nine CPAP group dogs. Treatment did not affect SpO2 (ß = -0.1, -2.1 to 2.0) but affected the PaO2/FiO2 ratio (ß = 58.1, 2.6 to 113.6), with no effects on PaCO2 (ß = -4.3, -10.5 to 1.9) or temperature (ß = 0.4, -0.8 to 1.6). CONCLUSION: In postoperative brachycephalic dogs, CPAP had no effect on SpO2 but improved the PaO2/FiO2 ratio in brachycephalic dogs postoperatively. CLINICAL SIGNIFICANCE: Continuous positive airway pressure offers a valuable solution to improve gas exchange efficiency, a prevalent concern in postoperative brachycephalic dogs, with the potential to enhance overall outcomes.

Tidal volume selection in volume-controlled ventilation guided by driving pressure versus actual body weight in healthy anesthetized and mechanically ventilated dogs: A randomized crossover trial.

OBJECTIVE: To compare static compliance of the respiratory system (CstRS) and the ratio of partial pressure of end-tidal to arterial carbon dioxide (Pe'CO2/PaCO2), in healthy dogs using two approaches for tidal volume (VT) selection during volume-controlled ventilation: body mass based and driving pressure (ΔPaw) guided. STUDY DESIGN: Randomized, nonblinded, crossover, clinical trial. ANIMALS: A total of 19 client-owned dogs anesthetized for castration and ovariohysterectomy. METHODS: After a stable 10 minute baseline, each dog was mechanically ventilated with a VT selection strategy, randomized to a constant VT of 15 mL kg-1 of actual body mass (VTBW) or ΔPaw-guided VT (VTΔP) of 7-8 cmH2O. Both strategies used an inspiratory time of 1 second, 20% end-inspiratory pause, 4 cmH2O positive end-expiratory pressure and fraction of inspired oxygen of 0.4. Respiratory frequency was adjusted to maintain Pe'CO2 between 35 and 40 mmHg. Respiratory mechanics, arterial blood gases and Pe'CO2/PaCO2 were assessed. Continuous variables are presented as mean ± SD or median (interquartile range; quartiles 1-3), depending on distribution, and compared with Wilcoxon signed-rank tests. RESULTS: The VT was significantly higher in dogs ventilated with VTΔP than with VTBW strategy (17.20 ± 4.04 versus 15.03 ± 0.60 mL kg-1, p = 0.036). CstRS was significantly higher with VTΔP than with VTBW strategy [2.47 (1.86-2.86) versus 2.25 (1.79-2.58) mL cmH2O-1 kg-1, p = 0.011]. There were no differences in Pe'CO2/PaCO2 between VTΔP and VTBW strategies (0.94 ± 0.06 versus 0.92 ± 0.06, p = 0.094). No discernible difference in ΔPaw was noted between the strategies. CONCLUSIONS AND CLINICAL RELEVANCE: While no apparent difference was observed in the Pe'CO2/PaCO2 between the VT selection strategies employed, CstRS significantly increased during the VTΔP approach. A future trial should explore if VTΔP improves perioperative gas exchange and prevents lung damage.

Three-dimensional electrical impedance tomography to study regional ventilation/perfusion ratios in anesthetized pigs.

This study aimed to develop a three-dimensional (3-D) method for assessing ventilation/perfusion (V/Q̇) ratios in a pig model of hemodynamic perturbations using electrical impedance tomography (EIT). To evaluate the physiological coherence of changes in EIT-derived V/Q̇ ratios, global EIT-derived V/Q̇ mismatches were compared with global gold standards. The study found regional heterogeneity in the distribution of V/Q̇ ratios in both the ventrodorsal and craniocaudal directions. Although global EIT-derived indices of V/Q̇ mismatch consistently underestimated both low and high V/Q̇ mismatch compared with global gold standards, the direction of the change was similar. We made the software available at no cost for other researchers to use. Future studies should compare regional V/Q̇ ratios determined by our method against other regional, high-resolution methods.NEW & NOTEWORTHY In this study, we introduce a novel 3-D method for assessing ventilation-perfusion (V/Q̇) ratios using electrical impedance tomography (EIT). Heterogeneity in V/Q̇ distribution showcases the significant potential for enhanced understanding of pulmonary conditions. This work signifies a substantial step forward in the application of EIT for monitoring and managing lung diseases.

Duration of neuromuscular block is more variable and recovery time is shorter with rocuronium than cisatracurium in anesthetized dogs.

OBJECTIVE: To compare the variability in the duration of action of a single dose of rocuronium or cisatracurium, and duration of subsequent top-up doses in anesthetized dogs. ANIMALS: Thirty dogs requiring ophthalmic surgery with neuromuscular block. PROCEDURES: Neuromuscular function was monitored with train-of-four (TOF) and acceleromyography. Dogs received an initial dose of rocuronium 0.6 mg/kg, or cisatracurium 0.15 mg/kg IV, which produced complete neuromuscular block. Upon return of the first response (T1) of TOF, a third of the initial dose was repeated. The duration of the initial dose and its variability were compared between agents. Duration of subsequent top-up doses was assessed with mixed effect models. Spontaneous (from last return of T1) or neostigmine-enhanced (from administration to complete recovery) recovery times were measured for each agent. RESULTS: Duration of action of the initial dose was [median (range)] 25 (10-60) min with rocuronium and 35 (15-45) min with cisatracurium (p = .231). The variability of rocuronium was 3.25 times larger than cisatracurium (p = .034). Duration of top-up doses did not vary for either agent. Spontaneous recovery was shorter for rocuronium [15 (10-20) min] than cisatracurium [25 (15-45) min] (p = .02). Neostigmine-enhanced recovery times were 5 (5-25) for rocuronium and 10 (5-10) for cisatracurium (p = .491). CONCLUSIONS: Duration of action for a single dose is significantly more variable with rocuronium than cisatracurium. Time to spontaneous recovery was longer for cisatracurium, and cases of unexpectedly long recovery times were observed with both agents. Objective monitoring is recommended.

Effect of end-inspiratory pause on airway and physiological dead space in anesthetized horses.

OBJECTIVE: To evaluate the impact of a 30% end-inspiratory pause (EIP) on alveolar tidal volume (VTalv), airway (VDaw) and physiological (VDphys) dead spaces in mechanically ventilated horses using volumetric capnography, and to evaluate the effect of EIP on carbon dioxide (CO2) elimination per breath (Vco2br-1), PaCO2, and the ratio of PaO2-to-fractional inspired oxygen (PaO2:FiO2). STUDY DESIGN: Prospective research study. ANIMALS: A group of eight healthy research horses undergoing laparotomy. METHODS: Anesthetized horses were mechanically ventilated as follows: 6 breaths minute-1, tidal volume (VT) 13 mL kg-1, inspiratory-to-expiratory time ratio 1:2, positive end-expiratory pressure 5 cmH2O and EIP 0%. Vco2br-1 and expired tidal volume (VTE) of 10 consecutive breaths were recorded 30 minutes after induction, after adding 30% EIP and upon EIP removal to construct volumetric capnograms. A stabilization period of 15 minutes was allowed between phases. Data were analyzed using a mixed-effect linear model. Significance was set at p < 0.05. RESULTS: The EIP decreased VDaw from 6.6 (6.1-6.7) to 5.5 (5.3-6.1) mL kg-1 (p < 0.001) and increased VTalv from 7.7 ± 0.7 to 8.6 ± 0.6 mL kg-1 (p = 0.002) without changing the VTE. The VDphys to VTE ratio decreased from 51.0% to 45.5% (p < 0.001) with EIP. The EIP also increased PaO2:FiO2 from 393.3 ± 160.7 to 450.5 ± 182.5 mmHg (52.5 ± 21.4 to 60.0 ± 24.3 kPa; p < 0.001) and Vco2br-1 from 0.49 (0.45-0.50) to 0.59 (0.45-0.61) mL kg-1 (p = 0.008) without reducing PaCO2. CONCLUSIONS AND CLINICAL RELEVANCE: The EIP improved oxygenation and reduced VDaw and VDphys, without reductions in PaCO2. Future studies should evaluate the impact of different EIP in healthy and pathological equine populations under anesthesia.

Lung aeration and volumes following alveolar recruitment maneuvers with three airway pressures in healthy anesthetized and mechanically ventilated Beagle dogs.

OBJECTIVE: To compare the effects of three recruitment airway pressures (RPaw) on lung aeration and volumes in mechanically ventilated dogs during propofol anesthesia. STUDY DESIGN: Prospective, crossover randomized experimental study. ANIMALS: A total of eight healthy anesthetized experimental Beagle dogs in dorsal recumbency. METHODS: Dogs were mechanically ventilated with a tidal volume of 15 mL kg-1 and zero positive end-expiratory pressure and 100% oxygen. Three maneuvers consisting of a 30 second inspiration at RPaws of 15 (RPaw15), 25 (RPaw25) and 35 (RPaw35) cmH2O were performed randomly, 15 minutes apart. Changes in lung aeration and lung deformation were compared with end-expiratory baseline (before the application of each RPaw) and between-RPaws using computed tomography scans and calculations of global lung strain. Between-group comparisons were performed with one-way anova for repeated measures followed by Tukey test for multiple comparisons. A p value < 0.05 was considered significant. RESULTS: The amount of nonaeration was minimal (<1%) at baseline and not different with the application of the RPaws. The amount of hypoaeration and normoaeration during baseline decreased with all RPaws (p < 0.001). There was no difference between RPaws regarding hypoaeration (all p > 0.999), whereas normoaeration was higher at RPaw15 than RPaw25 and RPaw35 (p < 0.009). Compared with baseline, the fraction of hyperaerated alveoli increased with each RPaw (p < 0.001) and was lower during RPaw15 than RPaw25 and RPaw35 (both p ≤ 0.007). Global lung strain was lower during RPaw15 than at higher RPaw (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: A RPaw of 15 cmH2O for 30 seconds was the recommended RPaw because it was as effective at reversing hypoaeration as RPaws of 25 and 35 cmH2O but with less hyperaeration and potential for overdistension of the lungs in this particular population of dogs with negligible atelectasis.

Effects of intraoperative positive end-expiratory pressure and fraction of inspired oxygen on postoperative oxygenation in dogs undergoing stifle surgery.

OBJECTIVE: To compare the effects of fraction of inspired oxygen (FiO2) with the addition of positive end-expiratory pressure (PEEP) during anesthesia on arterial oxygenation in the first 4 postoperative hours in dogs. We hypothesized that compared with dogs breathing FiO2 ≥ 0.95 and no PEEP (ZEEP), the use of intraoperative PEEP would improve postoperative oxygenation, and that the use of PEEP combined with an FiO2 of 0.4 would further improve it. STUDY DESIGN: Prospective, randomized study. ANIMALS: A total of 30 dogs undergoing unilateral stifle surgery. METHODS: Using a standardized anesthetic protocol, dogs were assigned to either FiO2 ≥ 0.95 and ZEEP, FiO2 ≥ 0.95 and 5 cmH2O PEEP or FiO2 0.4 and 5 cmH2O PEEP. All dogs were mechanically ventilated with a tidal volume of 12 mL kg-1. Dogs breathed room air after recovery from anesthesia. Arterial blood gases were measured during surgical closure and 10, 120 and 240 minutes after extubation. Demographic characteristics were compared with Kruskal-Wallis tests. The effects of treatment and time on the PaO2, PaCO2, PaO2:FiO2 and shunt fraction (F-shunt) were assessed with mixed-effect models. RESULTS: The PaO2 and F-shunt were lower during anesthesia for dogs breathing FiO2 0.4. No differences among groups were measured after extubation for any variable. CONCLUSIONS AND CLINICAL RELEVANCE: Compared with dogs ventilated with FiO2 ≥ 0.95 and ZEEP, application of 5 cmH2O PEEP did not improve intraoperative gas exchange. The combination of 5 cmH2O PEEP and FiO2 0.4 resulted in lower intraoperative F-shunt values. However, no benefits from those maneuvers on postoperative PaO2 and F-shunt were recorded after extubation, suggesting that alterations in pulmonary function imposed by anesthesia were reversed soon after extubation.

Preliminary evaluation of the effects of a 1:1 inspiratory-to-expiratory ratio in anesthetized and ventilated horses.

OBJECTIVE: To describe some cardiorespiratory effects of an inspiratory-to-expiratory (IE) ratio of 1:1 compared with 1:3 in ventilated horses in dorsal recumbency. STUDY DESIGN: Randomized crossover experimental study. ANIMALS: A total of eight anesthetized horses, with 444 (330-485) kg body weight [median (range)]. METHODS: Horses were ventilated in dorsal recumbency with a tidal volume of 15 mL kg-1 and a respiratory rate of 8 breaths minute-1, and IE ratios of 1:1 (IE1:1) and 1:3 (IE1:3) in random order, each for 25 minutes after applying a recruitment maneuver. Spirometry, arterial blood gases and dobutamine requirements were recorded in all horses during each treatment. Electrical impedance tomography (EIT) data were recorded in four horses and used to generate functional EIT variables including regional ventilation delay index (RVD), a measure of speed of lung inflation, and end-expiratory lung impedance (EELI), an indicator of functional residual capacity (FRC). Results were assessed with linear and generalized linear mixed models. RESULTS: Compared with treatment IE1:3, horses ventilated with treatment IE1:1 had higher mean airway pressures and respiratory system compliance (p < 0.014), while peak, end-inspiratory and driving airway pressures were lower (p < 0.001). No differences in arterial oxygenation or dobutamine requirements were observed. PaCO2 was lower in treatment IE1:1 (p = 0.039). Treatment IE1:1 resulted in lower RVD (p < 0.002) and higher EELI (p = 0.023) than treatment IE1:3. CONCLUSIONS AND CLINICAL RELEVANCE: These results suggest that IE1:1 improved respiratory system mechanics and alveolar ventilation compared with IE1:3, whereas oxygenation and dobutamine requirements were unchanged, although differences were small. In the four horses where EIT was evaluated, IE1:1 led to a faster inflation rate of the lung, possibly the result of increased FRC. The clinical relevance of these findings needs to be further investigated.

Effect of positive end-expiratory pressure on lung injury and haemodynamics during experimental acute respiratory distress syndrome treated with extracorporeal membrane oxygenation and near-apnoeic ventilation.

BACKGROUND: Lung rest has been recommended during extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS). Whether positive end-expiratory pressure (PEEP) confers lung protection during ECMO for severe ARDS is unclear. We compared the effects of three different PEEP levels whilst applying near-apnoeic ventilation in a model of severe ARDS treated with ECMO. METHODS: Acute respiratory distress syndrome was induced in anaesthetised adult male pigs by repeated saline lavage and injurious ventilation for 1.5 h. After ECMO was commenced, the pigs received standardised near-apnoeic ventilation for 24 h to maintain similar driving pressures and were randomly assigned to PEEP of 0, 10, or 20 cm H2O (n=7 per group). Respiratory and haemodynamic data were collected throughout the study. Histological injury was assessed by a pathologist masked to PEEP allocation. Lung oedema was estimated by wet-to-dry-weight ratio. RESULTS: All pigs developed severe ARDS. Oxygenation on ECMO improved with PEEP of 10 or 20 cm H2O, but did not in pigs allocated to PEEP of 0 cm H2O. Haemodynamic collapse refractory to norepinephrine (n=4) and early death (n=3) occurred after PEEP 20 cm H2O. The severity of lung injury was lowest after PEEP of 10 cm H2O in both dependent and non-dependent lung regions, compared with PEEP of 0 or 20 cm H2O. A higher wet-to-dry-weight ratio, indicating worse lung injury, was observed with PEEP of 0 cm H2O. Histological assessment suggested that lung injury was minimised with PEEP of 10 cm H2O. CONCLUSIONS: During near-apnoeic ventilation and ECMO in experimental severe ARDS, 10 cm H2O PEEP minimised lung injury and improved gas exchange without compromising haemodynamic stability.

Definition and clinical evaluation of a recruiting airway pressure based on the specific lung elastance in anesthetized dogs.

OBJECTIVE: To determine the specific lung elastance (SEL) in anesthetized dogs and to evaluate the efficacy of a SEL-based recruiting airway pressure (RPaw) at improving global and regional lung aeration. STUDY DESIGN: Retrospective and prospective clinical study. ANIMALS: A total of 28 adult dogs were included in the retrospective study and six adult dogs in the prospective study. METHODS: Retrospective study: SEL and SEL-based RPaw were determined using previously published data. In mechanically ventilated dogs undergoing thoracic computed tomography (CT), SEL was calculated as ΔPL/(VT/EELV), where ΔPL is the driving transpulmonary pressure, VT is the tidal volume and EELV is the end-expiratory lung volume. The ratio of lung to respiratory system elastance (EL/Ers) was determined. SEL and EL/Ers were used to calculate the SEL-based RPaw. Prospective study: dogs underwent thoracic CT at end-expiration and at end-inspiration using the SEL-based RPaw, and global and regional aeration was determined. For analysis of regional aeration, lungs were divided into cranial, intermediate and caudal regions. Regional compliance was also calculated. A p value <0.05 was considered significant. RESULTS: The SEL and EL/Ers were 12.7 ± 3.1 cmH2O and 0.54 ± 0.07, respectively. The SEL-based RPaw was 29.1 ± 7.6 cmH2O. In the prospective study, the RPaw was 28.2 ± 1.3 cmH2O. During RPaw, hyperinflation increased (p = 0.0003) whereas poorly aerated (p < 0.0001) and nonaerated (p = 0.01) tissue decreased. Normally aerated tissue did not change (p = 0.265). Regional compliance was higher in the intermediate (p = 0.0003) and caudal (p = 0.034) regions compared with the cranial region. Aeration did not differ between regions (p > 0.05). CONCLUSIONS AND CLINICAL RELEVANCE: An SEL-based RPaw reduces poorly and nonaerated lung tissue in anesthetized dogs. In nonsurgical anesthetized dogs, an RPaw near 30 cmH2O is effective at improving lung aeration.

Evaluation of noninvasive blood pressure in anesthetized horses: Bias, limits of agreement, and comparative detection of a predetermined mean blood pressure warranting treatment.

Oscillometric blood pressure monitoring may be a practical tool for short procedures or those performed outside of the operating room. Oscillometric and direct blood pressure values in 30 juvenile and adult horses in a clinical setting using mixed effect models were compared. The limits of agreement and percentage errors were also calculated. We evaluated the sensitivity and false positive rate for the oscillometric method to trigger an intervention for treating blood pressure [direct mean arterial pressure (MAP) < 70 mmHg]. Oscillometric MAP and diastolic arterial pressure (DAP) differed from direct values (P < 0.001); systolic arterial pressure (SAP) did not (P = 0.08). Wide limits of agreement were observed. Percentage errors were smaller for SAP (39%) than for MAP and DAP (48% and 72%). The oscillometric monitor indicated there was a requirement for blood pressure treatment with a true positive rate of 82%, consequently, it failed 18% of the times. The false positive rate (unnecessary treatment) was 55%.

Évaluation non invasive de la pression artérielle chez des chevaux anesthésiés: biais, limites d'accord et détection comparative d'une pression artérielle moyenne prédéterminée justifiant un traitement. La surveillance oscillométrique de la pression artérielle peut être un outil pratique pour les procédures courtes ou celles effectuées hors de la salle d'opération. Les valeurs oscillométriques et directes de la pression artérielle chez 30 chevaux juvéniles et adultes en milieu clinique ont été comparées à l'aide de modèles à effets mixtes. Les limites d'accord et les pourcentages d'erreurs furent également calculés. Nous avons évalué la sensibilité et le taux de faux positifs de la méthode oscillométrique pour déclencher une intervention pour le traitement de la pression artérielle [pression artérielle moyenne directe (PAM) < 70 mmHg]. La PAM oscillométrique et la pression artérielle diastolique (PAD) différaient des valeurs directes (P < 0,001); mais pas la pression artérielle systolique (PAS) (P = 0,08). De larges limites d'accord ont été observées. Les pourcentages d'erreurs étaient plus faibles pour PAS (39 %) que pour PAM et PAD (48 % et 72 %). Le moniteur oscillométrique a indiqué qu'il y avait une exigence pour un traitement de la pression artérielle avec un taux de vrais positifs de 82 %, par conséquent, il a échoué 18 % des fois. Le taux de faux positifs (traitement inutile) était de 55 %.(Traduit par Dr Serge Messier).

Low Spontaneous Breathing Effort during Extracorporeal Membrane Oxygenation in a Porcine Model of Severe Acute Respiratory Distress Syndrome.

BACKGROUND: A lung rest strategy is recommended during extracorporeal membrane oxygenation in severe acute respiratory distress syndrome (ARDS). However, spontaneous breathing modes are frequently used in this context. The impact of this approach may depend on the intensity of breathing efforts. The authors aimed to determine whether a low spontaneous breathing effort strategy increases lung injury, compared to a controlled near-apneic ventilation, in a porcine severe ARDS model assisted by extracorporeal membrane oxygenation. METHODS: Twelve female pigs were subjected to lung injury by repeated lavages, followed by 2-h injurious ventilation. Thereafter, animals were connected to venovenous extracorporeal membrane oxygenation and during the first 3 h, ventilated with near-apneic ventilation (positive end-expiratory pressure, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5/min). Then, animals were allocated into (1) near-apneic ventilation, which continued with the previous ventilatory settings; and (2) spontaneous breathing: neuromuscular blockers were stopped, sweep gas flow was decreased until regaining spontaneous efforts, and ventilation was switched to pressure support mode (pressure support, 10 cm H2O; positive end-expiratory pressure, 10 cm H2O). In both groups, sweep gas flow was adjusted to keep Paco2 between 30 and 50 mmHg. Respiratory and hemodynamic as well as electric impedance tomography data were collected. After 24 h, animals were euthanized and lungs extracted for histologic tissue analysis. RESULTS: Compared to near-apneic group, the spontaneous breathing group exhibited a higher respiratory rate (52 ± 17 vs. 5 ± 0 breaths/min; mean difference, 47; 95% CI, 34 to 59; P < 0.001), but similar tidal volume (2.3 ± 0.8 vs. 2.8 ± 0.4 ml/kg; mean difference, 0.6; 95% CI, -0.4 to 1.4; P = 0.983). Extracorporeal membrane oxygenation settings and gas exchange were similar between groups. Dorsal ventilation was higher in the spontaneous breathing group. No differences were observed regarding histologic lung injury. CONCLUSIONS: In an animal model of severe ARDS supported with extracorporeal membrane oxygenation, spontaneous breathing characterized by low-intensity efforts, high respiratory rates, and very low tidal volumes did not result in increased lung injury compared to controlled near-apneic ventilation.

Near-Apneic Ventilation Decreases Lung Injury and Fibroproliferation in an Acute Respiratory Distress Syndrome Model with Extracorporeal Membrane Oxygenation.

RATIONALE: There is wide variability in mechanical ventilation settings during extracorporeal membrane oxygenation (ECMO) in patients with acute respiratory distress syndrome. Although lung rest is recommended to prevent further injury, there is no evidence to support it. OBJECTIVES: To determine whether near-apneic ventilation decreases lung injury in a pig model of acute respiratory distress syndrome supported with ECMO. METHODS: Pigs (26-36 kg; n = 24) were anesthetized and connected to mechanical ventilation. In 18 animals lung injury was induced by a double-hit consisting of repeated saline lavages followed by 2 hours of injurious ventilation. Then, animals were connected to high-flow venovenous ECMO, and randomized into three groups: 1) nonprotective (positive end-expiratory pressure [PEEP], 5 cm H2O; Vt, 10 ml/kg; respiratory rate, 20 bpm), 2) conventional-protective (PEEP, 10 cm H2O; Vt, 6 ml/kg; respiratory rate, 20 bpm), and 3) near-apneic (PEEP, 10 cm H2O; driving pressure, 10 cm H2O; respiratory rate, 5 bpm). Six other pigs were used as sham. All groups were maintained during the 24-hour study period. MEASUREMENTS AND MAIN RESULTS: Minute ventilation and mechanical power were lower in the near-apneic group, but no differences were observed in oxygenation or compliance. Lung histology revealed less injury in the near-apneic group. Extensive immunohistochemical staining for myofibroblasts and procollagen III was observed in the nonprotective group, with the near-apneic group exhibiting the least alterations. Near-apneic group showed significantly less matrix metalloproteinase-2 and -9 activity. Histologic lung injury and fibroproliferation scores were positively correlated with driving pressure and mechanical power. CONCLUSIONS: In an acute respiratory distress syndrome model supported with ECMO, near-apneic ventilation decreased histologic lung injury and matrix metalloproteinase activity, and prevented the expression of myofibroblast markers.

Dynamic prediction of fluid responsiveness during positive pressure ventilation: a review of the physiology underlying heart-lung interactions and a critical interpretation.

OBJECTIVE: Cardiovascular responses to hypovolemia and hypotension are depressed during general anesthesia. A considerable number of anesthetized and critically ill animals may not benefit hemodynamically from a fluid bolus; therefore, it is important to have measures for accurate prediction of fluid responsiveness. Static measures of preload, such as central venous pressure, do not provide accurate prediction of fluid responsiveness, whereas dynamic measures of cardiovascular function, obtained during positive pressure ventilation, are highly predictive. This review describes key physiological concepts behind heart-lung interactions during positive pressure ventilation, factors that can modify this relationship and provides the basis for a rational interpretation of the information obtained from dynamic measurements, with a focus on pulse pressure variation (PPV). DATABASE USED: PubMed. Search items used were: heart-lung interaction, positive pressure ventilation, pulse pressure variation, dynamic index of fluid therapy, goal-directed hemodynamic therapy, dogs, cats, pigs, horses and rabbits. CONCLUSIONS: The veterinary literature suggests that targeting specific PPV thresholds should guide fluid therapy in lieu of conventional assessments. Understanding the physiology of heart-lung interactions during intermittent positive pressure ventilation provides a rational basis for interpreting the literature on dynamic indices of fluid responsiveness, including PPV. Clinical trials are needed to evaluate whether goal-directed fluid therapy based on PPV results in improved outcomes in veterinary patient populations.

Postoperative oxygenation in healthy dogs following mechanical ventilation with fractions of inspired oxygen of 0.4 or >0.9.

OBJECTIVE: To evaluate arterial oxygenation during the first 4 postoperative hours in dogs administered different fractions of inspired oxygen (FiO2) during general anesthesia with mechanical ventilation. STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: A total of 20 healthy female dogs, weighing >15 kg and body condition scores 3-7/9, admitted for ovariohysterectomy. METHODS: Dogs were randomized to breathe an FiO2 >0.9 or 0.4 during isoflurane anesthesia with intermittent positive pressure ventilation. The intraoperative PaO2:FiO2 ratio was recorded during closure of the linea alba. Arterial blood was obtained 5, 60 and 240 minutes after extubation for measurement of PaO2 and PaCO2 (FiO2 = 0.21). Demographic characteristics, duration of anesthesia, PaO2:FiO2 ratio and anesthetic agents were compared between groups with Wilcoxon tests. The postoperative PaO2, PaCO2, rectal temperature, a visual sedation score and events of hypoxemia (PaO2 < 80 mmHg) were compared between groups with mixed-effects models or generalized linear mixed models. RESULTS: Groups were indistinguishable by demographic characteristics, duration of anesthesia, anesthetic agents administered and intraoperative PaO2:FiO2 ratio (all p > 0.08). Postoperative PaO2, PaCO2, rectal temperature or sedation score were not different between groups (all p > 0.07). During the first 4 postoperative hours, hypoxemia occurred in three and seven dogs that breathed FiO2 >0.9 or 0.4 during anesthesia, respectively (p = 0.04). CONCLUSIONS AND CLINICAL RELEVANCE: The results identified no advantage to decreasing FiO2 to 0.4 during anesthesia with mechanical ventilation with respect to postoperative oxygenation. Moreover, the incidence of hypoxemia in the first 4 hours after anesthesia was higher in these dogs than in dogs breathing FiO2 >0.9.

Downregulation of SPARC Is Associated with Epithelial-Mesenchymal Transition and Low Differentiation State of Biliary Tract Cancer Cells.

BACKGROUND: Biliary tract cancers (BTCs) have a poor prognosis. BTCs are characterized by a prominent desmoplastic reaction which possibly contributes to the aggressive phenotype of this tumor. The desmoplastic reaction includes excessive production and deposition of extracellular matrix proteins such as periostin, secreted protein acidic and rich in cysteine (SPARC), thrombospondin-1, as well as accumulation of α-smooth muscle actin-positive cancer-associated fibroblasts and immune cells, secreting growth factors and cytokines including transforming growth factor (TGF)-ß. In the present study, we investigated the expression of SPARC in BTC as well as its possible regulation by TGF-ß. METHODS: Expression levels of Sparc, TGF-ß1 and its receptor ALK5 were evaluated by quantitative real-time PCR in 6 biliary tract cell lines as well as 1 immortalized cholangiocyte cell line (MMNK-1). RNAs from tumor samples of 7 biliary tract cancer patients were analyzed for expression of Sparc, TGF-ß type II receptor (TbRII) as well as Twist and ZO-1. MMNK-1 cells were stimulated with TGF-ß for 24 h, and Sparc, ZO-1 and E-Cadherin expressions were determined. The presence of SPARC protein was analyzed by immunohistochemistry in tumor specimens from 10 patients. RESULTS: When comparing basal Sparc transcript levels in diverse BTC cell lines to MMNK-1 cells, we found that it was strongly downregulated in all cancer cell lines. The remaining expression levels were higher in highly differentiated cell lines (CCSW1, MZChA1, MZChA2 and TFK-1) than in less differentiated and undifferentiated ones (BDC, SKChA1). Expression of Sparc in BTC patient samples showed a significant positive correlation with expression of the epithelial marker ZO-1. In contrast, the mesenchymal marker Twist and the TbRII showed a trend of negative correlation with expression of Sparc in these samples. TGF-ß exposure significantly downregulated Sparc expression in MMNK-1 cholangiocytes in vitro in parallel to downregulation of epithelial markers (E-Cadherin and ZO-1). Finally, SPARC immunostaining was performed in 10 patient samples, and the correlation between absence of SPARC and survival times was analyzed. CONCLUSIONS: These data imply that a decrease in SPARC expression is correlated with dedifferentiation of BTC cells resulting in enhanced EMT being possibly mediated by TGF-ß. Thereby SPARC levels might be a marker for individual prognosis of a patient, and strategies aiming at inhibition of SPARC downregulation might have potential for new future therapies.

Effects of positive end-expiratory pressure alone or an open-lung approach on recruited lung volumes and respiratory mechanics of mechanically ventilated horses.

OBJECTIVE: To evaluate the effects of positive end-expiratory pressure (PEEP) alone and PEEP preceded by lung recruitment manoeuvre (LRM) on lung volumes and respiratory system mechanics in healthy horses undergoing general anaesthesia. STUDY DESIGN: Controlled, prospective clinical study. ANIMALS: A group of 15 horses undergoing arthroscopy. METHODS: Following anaesthetic induction, initial ventilatory settings were: tidal volume 15 mL kg-1, inspiratory:expiratory ratio 1:2, respiratory rate to maintain end-tidal CO2 between 5.3-6.6 kPa (40-50 mmHg). The following settings were implemented sequentially: zero PEEP (ZEEP); PEEP 10 cmH2O (PEEP); LRM (50 cmH2O for 20 seconds) followed by 10 cmH2O of PEEP (LRM + PEEP). Static compliance (Cst), driving pressure, delta end-expiratory (ΔEELV) and recruited lung volumes (RLV) were obtained 30 minutes after initiating each ventilatory strategy. Data were analyzed with paired t test or analysis of variance followed by Tukey's post hoc test. Data are shown as mean ± standard deviation; p < 0.05 was considered significant. RESULTS: PEEP induced ΔEELV of 6.68 ± 3.36 mL kg-1; ΔEELV during LRM + PEEP was 14.28 ± 5.59 mL kg-1 (p < 0.0001). The RLV was greater during the LRM + PEEP phase (12.30 ± 5.85 mL kg-1) than during PEEP (4.47 ± 3.97 mL kg-1; p < 0.0001). The Cst was unchanged from ZEEP to PEEP (0.75 ± 0.21 and 0.85 ± 0.22 mL cmH2O-1 kg-1, respectively, p = 0.36) but increased using LRM + PEEP (1.11 ± 0.25 mL cmH2O-1 kg-1, p = 0.0004). Driving pressure was lower during LRM + PEEP than during PEEP and ZEEP (16 ± 2, 19 ± 2 and 21 ± 4 cmH2O, respectively, p < 0.0001). CONCLUSIONS AND CLINICAL RELEVANCE: Unlike PEEP alone, PEEP preceded by LRM increased RLV and Cst and reduced driving pressure in horses under anaesthesia.

Evaluation of Meropenem Pharmacokinetics in an Experimental Acute Respiratory Distress Syndrome (ARDS) Model during Extracorporeal Membrane Oxygenation (ECMO) by Using a PenP ß-Lactamase Biosensor.

INTRODUCTION: The use of antibiotics is mandatory in patients during extracorporeal membrane oxygenation (ECMO) support. Clinical studies have shown high variability in the antibiotic concentrations, as well as sequestration of them by the ECMO circuit, suggesting that the doses and/or interval administration used during ECMO may not be adequate. Thus, a fast response sensor to estimate antibiotic concentrations in this setting would contribute to improve dose adjustments. The biosensor PenP has been shown to have a dynamic range, sensitivity and specificity useful for pharmacokinetic (PK) tests in healthy subjects. However, the use of this biosensor in the context of a complex critical condition, such as ECMO during acute respiratory distress syndrome (ARDS), has not been tested. OBJECTIVES: To describe, by using PenP Biosensor, the pharmacokinetic of meropenem in a 24-h animal ARDS/ECMO model. METHODS: The PK of meropenem was evaluated in a swine model before and during ECMO. RESULTS: The PK parameters such as maximum concentration (Cmax), elimination rate constant (Ke), and cleareance (Cl), were not significantly altered during ECMO support. CONCLUSIONS: (a) ECMO does not affect the PK of meropenem, at least during the first 24 h; and (b) PenP has the potential to become an effective tool for making medical decisions associated with the dose model of antibiotics in a critical patient context.