Impact on cerebral hemodynamics of the use of volume guarantee combined with high frequency oscillatory ventilation in a neonatal animal respiratory distress model.

High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. However, the possible impact of this new ventilation technique on cerebral hemodynamics is unknown. To evaluate the cerebral hemodynamics effect of HFOV combined with VG in an experimental animal model of neonatal respiratory distress syndrome (RDS) due to surfactant deficiency compared with HFOV and CMV+VG (control group). Eighteen newborn piglets were randomized, before and after the induction of RDS by bronchoalveolar lavage, into 3 mechanical ventilation groups: CMV, HFOV and HFOV with VG. Changes in cerebral oxygen transport and consumption and cerebral blood flow were analyzed by non-invasive regional cerebral oxygen saturation (CrSO2), jugular venous saturation (SjO2), the calculated cerebral oxygen extraction fraction (COEF), the calculated cerebral fractional tissue oxygen extraction (cFTOE) and direct measurement of carotid artery flow. To analyze the temporal evolution of these variables, a mixed-effects linear regression model was constructed. After randomization, the following statistically significant results were found in every group: a drop in carotid artery flow: at a rate of -1.7 mL/kg/min (95% CI: -2.5 to -0.81; p < 0.001), CrSO2: at a rate of -6.2% (95% CI: -7.9 to -4.4; p < 0.001) and SjO2: at a rate of -20% (95% CI: -26 to -15; p < 0.001), accompanied by an increase in COEF: at a rate of 20% (95% CI: 15 to 26; p < 0.001) and cFTOE: at a rate of 0.07 (95% CI: 0.05 to 0.08; p < 0.001) in all groups. No statistically significant differences were found between the HFOV groups. CONCLUSION: No differences were observed at cerebral hemodynamic between respiratory assistance in HFOV with and without VG, being the latter ventilatory strategy equally safe. WHAT IS KNOWN: • Preterm have a situation of fragility of cerebral perfusion wich means that any mechanical ventilation strategy can have a significant influence. High-frequency oscillatory ventilation (HFOV) is an alternative to conventional mechanical ventilation (CMV). Recently, the use of volume guarantee (VG) combined with HFOV has been suggested as a safe strategy capable of reducing the damage induced by ventilation in immature lungs. Several studies have compared CMV and HFOV and their effects at hemodynamic level. It is known that the use of high mean airway pressure in HFOV can cause an increase in pulmonary vascular resistance with a decrease in thoracic venous return. WHAT IS NEW: • The possible impact of VAFO + VG on cerebral hemodynamics is unknown. Due the lack of studies and the existing controversy, we have carried out this research project in an experimental animal model with the aim of evaluating the cerebral hemodynamic repercussion of the use of VG in HFOV compared to the classic strategy without VG.

Individualizing mechanical ventilation: titration of driving pressure to pulmonary elastance through Young's modulus in an acute respiratory distress syndrome animal model.

BACKGROUND: Mechanical ventilation increases the risk of lung injury (VILI). Some authors propose that the way to reduce VILI is to find the threshold of driving pressure below which VILI is minimized. In this study, we propose a method to titrate the driving pressure to pulmonary elastance in an acute respiratory distress syndrome model using Young's modulus and its consequences on ventilatory-induced lung injury. MATERIAL AND METHODS: 20 Wistar Han male rats were used. After generating an acute respiratory distress syndrome, two groups were studied: (a) standard protective mechanical ventilation: 10 rats received 150 min of mechanical ventilation with driving pressure = 14 cm H2O, tidal volume < 6 mL/kg) and (b) individualized mechanical ventilation: 10 rats received 150 min of mechanical ventilation with an individualized driving pressure according to their Young's modulus. In both groups, an individualized PEEP was programmed in the same manner. We analyzed the concentration of IL-6, TNF-α, and IL-1ß in BAL and the acute lung injury score in lung tissue postmortem. RESULTS: Global driving pressure was different between the groups (14 vs 11 cm H2O, p = 0.03). The individualized mechanical ventilation group had lower concentrations in bronchoalveolar lavage of IL-6 (270 pg/mL vs 155 pg/mL, p = 0.02), TNF-α (292 pg/mL vs 139 pg/mL, p < 0.01) and IL-1ß (563 pg/mL vs 131 pg/mL, p = 0.05). They presented lower proportion of lymphocytes (96% vs 79%, p = 0.05) as well as lower lung injury score (6.0 points vs 2.0 points, p = 0.02). CONCLUSION: In our model, individualization of DP to pulmonary elastance through Young's modulus decreases lung inflammation and structural lung injury without a significant impact on oxygenation.

Safety and efficacy evaluation of the automatic stepwise recruitment maneuver in the neonatal population: An in vivo interventional study. Can anesthesiologists safely perform automatic lung recruitment maneuvers in neonates?

BACKGROUND: A new software has recently been incorporated in almost all new anesthesia machines to enable automatic lung recruitment maneuvers. To date, no studies have assessed the safety and efficacy of these automatic software programs in the neonatal population. AIMS: We aimed to evaluate the safety and efficacy of the lung recruitment maneuver performed using the automatic stepwise recruitment maneuver software of the FLOW-i 4.3 Anesthesia System® in a healthy and live neonatal model. METHODS: Eight male newborn piglets were included in the study. The lung recruitment maneuver was performed in pressure-controlled ventilation with a constant driving pressure (15 cmH2 O) in a stepwise increasing positive end-expiratory pressure (PEEP) model. The target peak inspiratory pressure (PIP) was 30 cmH2 O and PEEP was 15 cmH2 O. The maneuver lasted for 39 seconds. The hemodynamic variables were monitored using the PICCO® system. The following respiratory parameters were monitored: oxygen saturation, fraction of inspired oxygen, partial pressure of oxygen and carbon dioxide in the arterial blood, end-tidal carbon dioxide pressure, PIP, plateau pressure, PEEP, static compliance (Cstat ), and dynamic compliance (Cdyn ). Safety was evaluated by assessing the accuracy of the software, need for not interrupting the maneuver, hemodynamic stability, and absence of adverse respiratory events with the lung recruitment maneuver. Efficacy was evaluated by improvement in Cstat and Cdyn after performing the lung recruitment maneuver. RESULTS: All lung recruitment maneuvers were safely performed as scheduled without any interruptions. No pneumothorax or other side effects were observed. Hemodynamic stability was maintained during the lung recruitment maneuver. We observed an improvement of 33% in Cdyn and 24% in Cstat after the maneuver. CONCLUSIONS: The automatic stepwise recruitment maneuver software of the FLOW-i 4.3 Anesthesia System® is safe and efficacious in a healthy neonatal model. We did not observe any adverse respiratory or hemodynamic events during the implementation of the lung recruitment maneuver in the pressure-controlled ventilation mode using a stepwise increasing PEEP (30/15 cmH2 O) approach.

DCO2/PaCO2 correlation on high-frequency oscillatory ventilation combined with volume guarantee using increasing frequencies in an animal model.

To examine the correlation DCO2/PaCO2 on high-frequency oscillatory ventilation (HFOV) combined with volume guarantee (VG) throughout increasing frequencies in two different respiratory conditions, physiological and low compliance. Neonatal animal model was used, before and after a bronchoalveolar lavage (BAL). HFOV combined with VG was used. The frequency was increased from 10 to 20 Hz, and high-frequency tidal volume (VThf) was gradually decreased maintaining a constant DCO2. Arterial partial pressure of carbon dioxide (PaCO2) was evaluated after each frequency and VThf change. Six 2-day-old piglets were studied. A linear decrease in PaCO2 was observed throughout increasing frequencies in both respiratory conditions while maintaining a constant DCO2, showing a significant difference between the initial PaCO2 (at 10 Hz) and the PaCO2 obtained at 18 and 20 Hz. A new DCO2 equation (corrected DCO2) was calculated in order to better define the correlation between DCO2 and the observed PaCO2.Conclusion: The correlation DCO2/PaCO2 throughout increasing frequencies is not linear, showing a greater CO2 elimination efficiency at higher frequencies, in spite of maintaining a constant DCO2. So, using frequencies close to the resonant frequency of the respiratory system on HFOV combined with VG, optimizes the efficiency of gas exchange.What is Known: • The efficacy of CO2removal during high-frequency oscillatory ventilation (HFOV), described as the diffusion coefficient of CO2(DCO2) is related to the square of the high-frequency tidal volume (VThf) and the frequency (f), expressed as DCO2= VThf2× f.What is New: • The correlation between DCO2and PaCO2throughout increasing frequencies is not linear, showing a greater CO2elimination efficiency at higher frequencies. So, using very high frequencies on HFOV combined with volume guarantee optimizes the efficiency of gas exchange allowing to minimize lung injury.

Effects of intramuscular alfaxalone alone or in combination with diazepam in swine.

OBJECTIVE: To describe the use of intramuscular (IM) premedication with alfaxalone alone or in combination with diazepam in pigs. STUDY DESIGN: Randomised-controlled trial. ANIMALS: Twelve healthy 2 month-old Landrace x Large White pigs weighing 21.3 ± 2.4 kg. METHODS: Animals were distributed randomly into two groups: group A (n = 6) 5 mg kg(-1) of IM alfaxalone; and group AD (n = 6) 5 mg kg(-1) of IM alfaxalone + 0.5 mg kg(-1) of IM diazepam mixed in the same syringe. The total volume of injectate was standardized at 14 mL by dilution in 0.9% sodium chloride. Pain on injection, the degree of sedation and the quality of and time to induction of recumbency were evaluated. Once pigs were recumbent, reflexes were evaluated. Pulse and respiratory rates and arterial oxygen saturation were recorded at 5 and 10 minutes after drug administration. Pigs were then moved to another room for subsequent anaesthesia. RESULTS: Two animals of group A and one of group AD showed slight pain on drug injection. Time to lateral recumbency (in seconds) was shorter in group AD (mean 203 ± SD 45 range 140-260) than group A (302 ± 75, range 220-420; p < 0.05). In group AD sedation was deeper, and on recumbency there was better muscle relaxation. When moved for anaesthesia, two pigs in Group A showed slight resistance but did not vocalize. There were no differences in physiologic measurements between groups, although in both groups, respiratory rate was significantly lower at ten compared with five minutes post drug injection. There was no apneoa. CONCLUSIONS AND CLINICAL RELEVANCE: IM administration of alfaxalone combined with diazepam resulted in a rapid onset of recumbency and deep sedation, with minimal side effects. The combination might be useful for premedication, but volume of injectate will limit its use to small pigs.

Shortened Automatic Lung Recruitment Maneuvers in an In Vivo Model of Neonatal ARDS.

BACKGROUND: The aim of this study was to assess the safety and efficacy of 2 protocols for automatic lung recruitment maneuvers (LRMs) using stepwise increases in PEEP in a neonatal ARDS model. These protocols were designed with lower maximum opening pressures than traditional methods and differ each one in the duration of the opening phases (short vs prolonged). We described hemodynamic changes through invasive monitoring, and we analyzed if the behavior of the variables depends on the duration of the opening phase of the LRM. METHODS: We designed a prospective, experimental study with 10 Landrace x Large White pigs < 48 h old. Under general anesthesia, tracheal intubation, invasive hemodynamic monitoring with a pediatric arterial thermodilution catheter was performed. An ARDS model was developed with bronchoalveolar lavages. Two types of LRMs were performed in each piglet, with a maximum peak inspiratory pressure (PIP) of 30 cm H2O and a PEEP 15 cm H2O applied during 8.5 s in the short LRM and 17 s in the prolonged LRM. A comparative analysis by virtue of the Wilcoxon signed-rank test and a regression analysis using generalized estimation equation were performed. RESULTS: We found that both LRMs were effective regarding oxygenation and respiratory mechanics. Shortening the duration of the opening phase and lowering the maximum opening pressures to PIP 30 and PEEP 15 cm H2O were above the critical opening pressure to reverse alveolar collapse in our neonatal ARDS model. Although we observed hemodynamic variations during both types of LRMs, these were well tolerated. CONCLUSIONS: Our LRM protocols exceeded critical opening pressures to reverse alveolar collapse in our neonatal ARDS model. This range of pressures might involve less hemodynamic disturbance. Duration of the maximum opening pressure step is a determining factor for hemodynamic alterations.

Impact of Stepwise Recruitment Maneuvers on Cerebral Hemodynamics: Experimental Study in Neonatal Model.

BACKGROUND: Lung recruitment maneuvers (LRMs) have been demonstrated to be effective in avoiding atelectasis during general anesthesia in the pediatric population. Performing these maneuvers is safe at the systemic hemodynamic and respiratory levels. AIMS: We aimed to evaluate the impact of a stepwise LRM and individualized positive end-expiratory pressure (PEEP) on cerebral hemodynamics in an experimental neonatal model. METHODS: Eleven newborn pigs (less than 72 h old, 2.56 ± 0.18 kg in weight) were included in the study. The LRM was performed under pressure-controlled ventilation with a constant driving pressure (15 cmH2O) in a stepwise increasing PEEP model. The target peak inspiratory pressure (PIP) was 30 cmH2O and the PEEP was 15 cmH2O. The following hemodynamic variables were monitored using the PICCO® system: mean arterial pressure (MAP), central venous pressure (CVP), and cardiac output (CO). The cerebral hemodynamics variables monitored were intracranial pressure (ICP) (with an intraparenchymal Camino® catheter) and cerebral oxygen saturation (rSO2) (with the oximetry monitor INVOS 5100® system). The following respiratory parameters were monitored: oxygen saturation, fraction of inspired oxygen, partial pressure of oxygen, end-tidal carbon dioxide pressure, Pmean, PEEP, static compliance (Cstat), and dynamic compliance (Cdyn). RESULTS: All LRMs were safely performed as scheduled without any interruptions. Systemic hemodynamic stability was maintained during the lung recruitment maneuver. No changes in ICP occurred. We observed an improvement in rSO2 after the maneuver (+5.8%). CONCLUSIONS: Stepwise LRMs are a safe tool to avoid atelectasis. We did not observe an impairment in cerebral hemodynamics but an improvement in cerebral oxygenation.

High-frequency Ventilation.

High-frequency ventilation (HFV) is an alternative to conventional mechanical ventilation, with theoretic benefits of less risk of ventilator lung injury and more effectivity in washout CO2. Previous clinical studies have not demonstrated advantages of HFV in preterm infants compared with conventional ventilation, so rescue HFV has been used when severe respiratory insufficiency needs aggressive ventilator settings in immature infants. Today it is possible to measure, set directly, and fix tidal volume, which can protect the immature lung from large volumes and fluctuations of the tidal volume. This strategy can be used in preterm infants with respiratory failure needing invasive ventilation.

New indicators for optimal lung recruitment during high frequency oscillator ventilation.

Previous research has demonstrated the potential benefit derived from the combination of high frequency oscillatory ventilation and volume guarantee mode (HFOV-VG), a procedure that allows us to explore and control very low tidal volumes. We hypothesized that secondary spontaneous change in oscillation pressure amplitude (∆Phf), while increasing the mean airway pressure (MAP) using HFOV-VG can target the lung recruitment. METHODS: A two-step animal distress model study was designed; in the first-step (ex vivo model), the animal's lungs were isolated to visually check lung recruitment and, in the second one (in vivo model), they were checked through arterial oxygen partial pressure improvement. Baseline measurements were performed, ventilation was set for 10 min and followed by bronchoalveolar lavage with isotonic saline to induce depletion of surfactant and thereby achieve a low compliance lung model. The high-frequency tidal volume and frequency remained constant and the MAP was increased by 2 cmH2 O (ex vivo) and 3 cmH2 O steps (in vivo) every 2 min. Changes in ΔPhf to achieve the fixed volume were recorded at the end of each interval to describe the maximum drop point as the recruitment point. RESULTS: Fourteen Wistar Han rats were included, seven on each sub-study described. After gradual MAP increments, a progressive decrease in ΔPhf related to recruited lung regions was visually demonstrated. In the in vivo model we detected a significant comparative decrease of ΔPhf, when measured against the previous value, after reaching a MAP of 11 cmH2 O up to 17 cmH2 O, correlating with a significant improvement in oxygenation. CONCLUSION: The changes in ∆Phf, linked to a progressive increase in MAP during HFOV-VG, might identify optimal lung recruitment and could potentially be used as an additional lung recruitment marker.

Use of very low tidal volumes during high-frequency ventilation reduces ventilator lung injury.

The use of volume guarantee (VG) on high-frequency oscillatory ventilation (HFOV) allows to use fixed very low high-frequency tidal volume (VThf), maintaining adequate CO2 removal while potentially reducing the risk of ventilator-induced lung injury. OBJECTIVE: To demonstrate that the use of very low VThf can be protective compared with standard VThf on HFOV combined with VG in a neonatal animal model. STUDY DESIGN: Experimental study in 2-day-old piglets with induced respiratory distress syndrome ventilated with two different HFOV strategies combined with VG (10 Hz with high VThf versus 20 Hz with very low VThf at similar PaCO2). After 12 h of mechanical ventilation, the pulmonary histologic pattern was analyzed. RESULTS: We found in the 10 Hz group with the higher VThf compared with the 20 Hz and very low VThf group more evident and more severe histological lesions with inflammatory infiltrate within the alveolar wall and alveolar space, as well as large areas of parenchyma consolidation and areas of alveolar hemorrhage in the more severe cases. CONCLUSION: The use of very low VThf compared with higher VThf at similar CO2 removal reduces lung injury in a neonatal animal model of lung injury after prolonged mechanical ventilation with HFOV combined with VG.

Effects of lidocaine, dexmedetomidine or their combination on the minimum alveolar concentration of sevoflurane in dogs.

The aim of this study was to determine the effects of lidocaine (LIDO) and dexmedetomidine (DEX) or their combination (LIDO-DEX), administered by constant-rate infusion (CRI), on the minimum alveolar concentration (MAC) of sevoflurane in dogs. Seven healthy mongrel dogs were used with a 2-week washout interval between treatments in this study. Anesthesia was induced with propofol and maintained with sevoflurane in oxygen, and MAC of sevoflurane was determined after 90 min equilibration period in the dogs (SEV-MACBASAL). Then, sevoflurane MAC was determined again in the dogs after 45 min equilibration period of one of the following treatments: an intravenous loading dose of lidocaine 2 mg/kg followed by 6 mg/kg/hr CRI (SEV-MACLIDO); an intravenous loading dose of dexmedetomidine 2 µg/kg followed by 2 µg/kg/hr CRI (SEV-MACDEX); or their combination (SEV-MACLIDO-DEX). These SEV-MACs were determined in duplicate. Data were analyzed using ANOVA and post hoc Tuckey test when appropriate. The SEV-MACBASAL was 1.82 ± 0.06%, SEV-MACLIDO was 1.38 ± 0.08%, SEV-MACDEX was 1.22 ± 0.10%, and SEV-MACLIDO-DEX was 0.78 ± 0.06%. The CRI administration of lidocaine, dexmedetomidine and their combination produced a significant reduction in the MAC of sevoflurane by 26.1 ± 9.0% (P<0.0001), 43.7 ± 11.8% (P<0.0002) and 54.4 ± 9.8% (P<0.0001), respectively. The MAC reduction was significantly greater after the CRI combination of lidocaine and dexmedetomidine when compared with lidocaine CRI (P<0.0001) or dexmedetomidine CRI treatments (P<0.025).

Lidocaine, dexmedetomidine and their combination reduce isoflurane minimum alveolar concentration in dogs.

The effects of intravenous (i.v.) lidocaine, dexmedetomidine and their combination delivered as a bolus followed by a constant rate infusion (CRI) on the minimum alveolar concentration of isoflurane (MACISO) in dogs were evaluated. Seven healthy adult dogs were included. Anaesthesia was induced with propofol and maintained with isoflurane. For each dog, baseline MAC (MACISO/BASAL) was determined after a 90-minute equilibration period. Thereafter, each dog received one of the following treatments (loading dose, CRI): lidocaine 2 mg kg(-1), 100 µg kg(-1) minute(-1); dexmedetomidine 2 µg kg(-1), 2 µg kg(-1) hour(-1); or their combination. MAC was then determined again after 45- minutes of treatment by CRI. At the doses administered, lidocaine, dexmedetomidine and their combination significantly reduced MACISO by 27.3% (range: 12.5-39.2%), 43.4% (33.3-53.3%) and 60.9% (46.1-78.1%), respectively, when compared to MACISO/BASAL. The combination resulted in a greater MACISO reduction than the two drugs alone. Their use, at the doses studied, provides a clinically important reduction in the concentration of ISO during anaesthesia in dogs.

High-frequency oscillatory ventilation combined with volume guarantee in a neonatal animal model of respiratory distress syndrome.

Objective. To assess volume guarantee (VG) ventilation combined with high-frequency oscillatory ventilation (HFOV) strategy on PaCO2 regulation in an experimental model of neonatal distress syndrome. Methods. Six 2-day-old piglets weighing 2.57 ± 0.26 kg were used for this interventional experimental study. Animals were ventilated during physiologic lung conditions and after depletion of lung surfactant by bronchoalveolar lavage (BAL). The effect of HFOV combined with VG on PaCO2 was evaluated at different high-frequency expired tidal volume (VThf) at constant frequency (f R ) and mean airway pressure (mPaw). Fluctuations of the pressure (ΔPhf) around the mPaw and PaCO2 were analyzed before and after lung surfactant depletion. Results. PaCO2 levels were inversely proportional to VThf. In the physiological lung condition, an increase in VThf caused a significant decrease in PaCO2 and an increase in ΔPhf. After BAL, PaCO2 did not change as compared with pre-BAL situation as the VThf remained constant by the ventilator. Conclusions. In this animal model, using HFOV combined with VG, changes in the VThf settings induced significant modifications in PaCO2. After changing the lung condition by depletion of surfactant, PaCO2 remained unchanged, as the VThf setting was maintained constant by modifications in the ΔPhf done by the ventilator.