Mechanical ventilation with a strategy based on restriction of tidal volumes (Vt) and inflation pressures improves outcome in patients with acute lung injury or acute respiratory distress syndrome (ARDS) (1). Using small Vt for ventilatory management may result in alveolar collapse. In addition, the risk of lung unit collapse is further enhanced if a high fraction of inspiratory oxygen (Fio2) is used (2) or if tracheal suctioning is performed (3,4). Recruitment maneuvers (RM) based on sustained inflation with higher pressures have been advocated (5) to promote alveolar recruitment and improve pulmonary gas exchange (5,6). Data on the physiologic effects of RM on regional blood flows are scarce. The high intrathoracic pressures used for RM may result in detrimental effects on hemodynamics (5,7–9). Despite improved arterial oxygenation, an increase in intrathoracic pressure may impede tissue oxygen delivery (10–12). Tissue perfusion and oxygen delivery are often compromised in mechanically-ventilated patients and hence RM may improve gas exchange and lung mechanics but cause impaired perfusion of other vital organs.
The aim of the present study was to assess the physiologic effects of a RM on hemodynamics in general and on splanchnic hemodynamics in particular. We hypothesized that such a maneuver would have an effect similar to hypovolemia, that is, that it would produce a sustained redistribution of blood flow away from the splanchnic region (13) while cerebral autoregulation would restore circulation to the brain (14). To test our hypothesis, we assessed the effect of a RM using a sustained inflation to 40 cm H2O (5,15) in healthy animal lungs on carotid, total splanchnic (celiac trunk + superior mesenteric artery), splenic, hepatic, and renal artery, as well as on portal vein flows. In addition, we assessed the effect of RM on pulmonary, carotid, femoral, and hepatic artery pressures, as well as on hepatic and portal vein pressures. Blood gases and respiratory mechanics were also studied.
The study protocol was approved by the Ethics Committee for animal experiments. Ten pigs of both sexes (37–42 kg) were deprived of food but not water 24 h before the experiments. Premedication with atropine 0.05 mg/kg, xylazin 2 mg/kg and ketamine 20 mg/kg IM was followed by cannulation of an ear vein and IV administration of 5–15 mg/kg thiopental for endotracheal intubation. Anesthesia was maintained with thiopental (5 mg · kg−1·· h−1) and fentanyl (30 μg · kg−1·· h−1 until the end of surgery, 5 μg · kg−1·· h−1 thereafter). The animals were ventilated with a volume-controlled mode (Servo 900C, Siemens, Erlangen, Germany) with 5 cm H2O of positive end-expiratory pressure (PEEP). Fio2 (0.4–0.6) was adjusted to keep arterial oxygen partial pressure (PaO2) levels between 100 mm Hg and 150 mm Hg. Vt was kept at 10 mL/kg and the minute ventilation was adjusted to maintain arterial carbon dioxide partial pressure (PaCO2) levels between 34 – 41 mm Hg.
A pulmonary artery catheter (via the left internal jugular vein) and a femoral arterial catheter were inserted. A fluid-filled catheter was inserted into the carotid artery, and an ultrasound transit time flow probe (Transonic™ Systems, Ithaca, NY) was placed around the artery. A large-bore catheter for fluid administration was inserted into the femoral vein. The abdominal cavity was opened by a midline abdominal incision. A drainage catheter was inserted into the urinary bladder. The celiac trunk, superior mesenteric, hepatic, splenic, and renal arteries and the portal vein were exposed and ultrasound transit time flow probes (Transonic™ Systems) were placed around the vessels. Two fluid-filled catheters were inserted into a mesenteric vein. The tip of the first catheter was placed into the portal vein and the tip of the second catheter remained in the mesenteric vein. A catheter was inserted into the hepatic artery via the left gastric artery. A hepatic vein catheter was inserted via the right internal jugular vein. The catheter was withdrawn 0.5–1.0 cm from the wedge position to allow measurement of hepatic venous pressure and saturation. During surgery, the animals received 5 mL · kg−1·· h−1 infusions of saline, Ringer’s lactate solution, and gelatin. Additional fluid was administered if necessary to keep pulmonary artery occlusion pressure (PAOP) between 5 and 8 mm Hg. Body temperature of the animals was kept at more than 38°C using an operating table heater and warmed fluids when necessary. After instrumentation, the abdomen wall remained open and gelatin infusion was stopped.
Two hours of hemodynamic stabilization were allowed after surgery. To avoid hypovolemia, volume loading with gelatin (5–10 mL/kg) was titrated to maintain stable hemodynamics (PAOP 5–8 mm Hg, mean systemic arterial blood pressures >60 mm Hg and urinary output >0.5 mL · kg−1 · h−1). Thereafter, neuromuscular relaxation was obtained by administering a 0.1 mg/kg bolus of pancuronium, and baseline hemodynamic data were recorded. A RM followed. Hemodynamic data were recorded at intervals until 8 min after the RM. Arterial blood gases and static mechanics of the respiratory system were measured just before and at 8 min after the RM (Fig. 1).
The RM was performed according to a previously described procedure (16). While being ventilated at baseline, the animals were disconnected from the ventilator and allowed to exhale to functional residual capacity (FRC) for 5–7 s. This was done during an end-expiratory pause of the ventilator. At the same time, ventilator settings were changed to pressure-controlled mode with an inspiratory pressure of 35 cm H2O added to a PEEP level of 5 cm H2O, a respiratory frequency of 6 bpm, and an inspiratory time of 80% of the total respirator cycle. The animals were then reconnected to the ventilator, the end-expiratory pause button was released, and the inspiratory-hold button was pressed. This resulted in an active inspiration to an inspiratory pressure of 40 cm H2O for 8 s followed by a maintained end-inspiratory pressure at 40 cm H2O for a further 12 s. During this end-inspiratory pause, baseline settings were reintroduced in the ventilator and baseline ventilation was resumed immediately thereafter.
Static mechanics of the respiratory system were assessed as described by Rossi et al. (17). Airway pressure was measured via a side hole placed between the pneumotachometer and the endotracheal tube with a pressure transducer (TG-100, ±10 kPa; Scireq, Montreal, PQ). Static pressures of the respiratory system were measured by occluding the airway for 5 s at end-expiration (total PEEP, PEEPtot) and end-inspiration (inspiratory static pressure, Pst,insp) during separate respiratory cycles. PEEPtot includes components of the external PEEP set by the ventilator (PEEPset), and intrinsic PEEP (PEEPi), i.e., PEEPtot = PEEPset + PEEPi (18). To assess volume, we used the digitally integrated flow signal from a heated pneumotachometer (3830B; Hans Rudolph, Kansas City, MO), connected to a differential pressure transducer (TD-05, ± 0,5 kPa, Scireq). Static compliance (Cst,rs) was calculated as a ratio of volume change over pressure change (17): Cst,rs = Vt/(Pst,insp − PEEPtot).
During an end-expiratory pause, the animals were disconnected from the ventilator and allowed to expire to FRC. This was done immediately before and at 8 min after the RM to estimate the effect of alveolar recruitment on end-expiratory lung volume. On both occasions, this measurement was done after the measurement of Cst,rs. The volume exhaled after disconnection from the ventilator, starting from zero flow at end-expiration during baseline ventilation until zero flow during disconnection, was defined as change in end-expiratory lung volume (dEELV).
Carotid and pulmonary arterial, central venous, hepatic venous, and portal venous blood pressures, and PAOP were recorded with quartz pressure transducers and displayed continuously on a multimodular monitor (S/5 Compact Critical Care Monitor, Datex-Ohmeda™, Helsinki, Finland) and recorded (see below). All pressure transducers were calibrated simultaneously and zeroed to the level of the heart. Cardiac output (L/min) was measured by a thermodilution technique (mean value of 3 measurements, cardiac output module; Datex-Ohmeda™). Regional blood flow signals were displayed continuously on dual channel flowmeters (T206; Transonic™ System). Heart rate was measured from the electrocardiogram, which was also continuously monitored.
Total resistance across the splanchnic bed (splanchnic vascular resistance) was calculated as Pressure (femoral artery − hepatic vein)/flow (celiac trunk + superior mesenteric artery).
We assessed the difference between central venous pressure and airway pressure (CVP − Paw) as a surrogate for right heart transmural pressure and preload.
Arterial and mixed venous blood samples were taken after measurement of Cst,rs and lung volumes (see above). Blood gases were analyzed immediately with a standard technique (ABL 520, Radiometer, Copenhagen, Denmark). Hemoglobin concentrations and oxygen saturations were measured with an analyzer designed for porcine blood (OSM 3; Radiometer, Copenhagen, Denmark).
Femoral and hepatic arterial pressures, hepatic and portal venous pressures, celiac trunk, superior mesenteric, hepatic, splenic, renal, and carotid arterial flows, as well as portal venous flow values were collected at 20 Hz by Windaq™ 1.60 (Dataq Instruments Inc., Akron, OH). Carotid, pulmonary arterial, and central venous pressures, as well as airway flow and pressure, were recorded at 100 Hz by AcqKnowledge™, Version 3.7.0 (Biopac Systems, Inc., Goleta, CA). Mean values from all the collected blood flow and pressure values were obtained from 7 time periods: 1) for 60 s at baseline (2 h after surgery and immediately before the RM), 2) for 5 s at the beginning of the RM (start RM), 3) for 5 s at the end of the RM (end RM), 4) for 20 s at 65 s after the end of the RM (65 RM), and 5–7) for 60 s at 3, 5, and 8 min after the end of the RM (3 RM, 5 RM, and 8 RM, respectively) (Fig. 1). This analysis protocol was established to obtain more detailed data during and immediately after the RM, and thus better characterize the acute changes in hemodynamics because of the RM. Moreover, data collected by Windaq™ 1.60 (Dataq Instruments) were also assessed at 60, 40, and 20 min before RM, for 60-s periods, to ensure stability of signals.
We calculated the mean values from each variable over the studied periods of time in every animal, and used these values for further calculations. A normal distribution of the obtained data could not be assumed because of the small study population. Data were therefore presented as median (25th–75th percentiles) and nonparametric statistical tests were used. Baseline values were compared to values during and after the RM (start RM, end RM, 65 RM, 3 RM, 5 RM, and 8 RM) and also to values before the RM (60, 40, and 20) using the Friedman two-way analysis of variance. When the Friedman test was found significant, Wilcoxon’s signed-rank test was used to compare baseline to each of the values obtained at the precedent or subsequent time points. Two-tailed tests were used, and Bonferroni correction was applied. To compare the variables (blood gases and respiratory mechanics) obtained only at baseline and at the end of the experiment, the Wilcoxon’s signed rank test was used. For all statistical analyses, we used the SPSS software (SPSS™ 11.5 for Windows, SPSS Inc., Chicago, IL). A P value of <0.05 was considered significant.
Because of technical problems, data on carotid artery, pulmonary artery, hepatic venous, portal venous pressures, and CVP and respiratory mechanics are not available for 3 animals. The remaining data on blood pressures and flows, as well as on blood gases, were collected from all animals.
After the stabilization period and before the RM, the mean cardiac output was 4.2 (3.4–4.7) L/min and the mean PAOP was 4.5 (4.0–5.0) mm Hg. Flows and pressures remained stable during the 60 min before the RM, except for an increase in celiac trunk and hepatic arterial flows (P = 0.040). All flows decreased during the RM (P = 0.030). Total splanchnic, renal arterial and portal venous flows were still decreased 8 min after the maneuver (P ≤ 0.042) (Fig. 2, Table 1). Hepatic and femoral arterial pressures decreased during the RM (P ≤ 0.048), whereas portal and hepatic venous pressures increased (P = 0.030) (Fig. 3). These pressures returned to baseline levels at 8 min after the maneuver (Fig. 3). Carotid pressure decreased, whereas pulmonary arterial pressure and CVP increased during the RM (Fig. 4). These changes did not reach statistical significance. All pressures returned to baseline levels at 8 min after the maneuver (Fig. 4). At 65 s after the RM, all flows and pressures had returned to 75%–109% of baseline (Figs. 2–4). Right heart transmural pressures (CVP − Paw) tended to decrease during the maneuver (P = 0.108) but returned to baseline levels at 65 s after the end of the maneuver (Fig. 4). Splanchnic vascular resistance increased at the start of the RM but quickly returned to baseline levels (Fig. 5). Heart rate did not change during or after the maneuver as compared to baseline.
PaO2, mixed venous oxygen saturation (SvO2), and pulmonary shunt (QS/QT) did not change, whereas peak inspiratory airway pressure (Paw,peak) decreased and Cst,rs and dEELV increased after the RM (Table 2).
RM have been advocated as a complement to mechanical ventilation during anesthesia (19), in the postoperative period (20), and in patients with ARDS (5). They produce high pressures or volumes that might have a detrimental effect on hemodynamics per se (7,9). We found that a RM performed in healthy animal lungs produced a marked, though transitory, impairment of total splanchnic, hepatic, splenic, renal, and carotid arterial and portal venous blood flows, induced a marginal decrease in total splanchnic, renal and portal blood flows at 8 minutes after the maneuver, improved respiratory mechanics, and did not affect oxygenation and pulmonary shunt.
Few studies have addressed the adverse effects and complications of RMs. In some small clinical trials, transient moderate decreases of systemic pressures have been reported (5,6,21) as well as a transient impairment of cerebral hemodynamics and metabolism (14). Pneumothorax and bacterial translocation have not been associated with RMs, however (6,19,22). Clinically relevant levels of PEEP have been shown to decrease splanchnic blood flow when associated with a decreased cardiac output (10–12). However, no effect of PEEP on splanchnic blood flow could be detected during stable hemodynamics (23). In animal models, marked effects of the RM on systemic hemodynamics have been described (8,9), but no data have been presented concerning the effect of a RM on the different vascular beds of the intraabdominal circulation.
Our data show a marked impairment of systemic and regional circulation during the RM, followed by a quick recovery to close to baseline levels. Nevertheless, a small but significant impairment of total splanchnic, renal, and portal blood flows persisted at 8 minutes after the maneuver. This impairment might have very limited or no clinical relevance in healthy animals or humans. Small decreases in regional perfusion may become detrimental in conditions of impaired cerebral perfusion, however (e.g., atherosclerosis or increased intracranial pressure), or in sepsis, when splanchnic perfusion does not meet the increased metabolic demands. Because of the short nature of our experiment, we cannot draw any conclusions as to the long-term effects of this impairment. We observed a decrease in our surrogate for right heart transmural pressure/preload (CVP − Paw) during the RM. Negative transmural pressures could be responsible for a decrease in venous return and cardiac output, which could explain at least in part the observed simultaneous impairment of regional blood flows. Odenstedt et al. (8,9) have shown a decrease in the hemodynamic effects of a RM after volume expansion (dextran 8 mL/kg). In our study, similar fluid volumes were administered before the RM (gelatin 5–10 mL/kg). Moreover, celiac trunk and hepatic artery flows increased during the 60 minutes preceding RM. This could be attributed to intravascular fluid administration during the stabilization period. This suggests that our results are not a result of hypovolemia per se. We cannot, however, completely exclude some hemodynamic instability during the experiment because of the discontinuation of gelatin infusion, especially in those animals requiring higher levels of intravascular fluid administration.
We found a 29% increase in compliance after the RM but no improvement in arterial oxygenation. Markström et al. (24) have obtained comparable results in a similar setting. These authors argue that, in the pig, intact hypoxic vasoconstriction reflexes during anesthesia could avoid perfusion of unventilated, collapsed lung units, thus preventing a clear effect of a RM on blood gases (24). The same could have happened in our study. In humans, and during anesthesia, the change over time in the amount of atelectasis and pulmonary shunt is independent of the change in Cst,rs (2). Similarly, even though the RM resulted in a significant increase in Cst,rs, no change in pulmonary shunt was found in the present study. Our results, with a lack of change in shunt, could also be explained by an absence of atelectasis during surgery and stabilization because of high Vt (10 mL/kg) and low intraabdominal pressure (open abdomen wall). In addition, the measurements of respiratory mechanics were performed before the disconnection from the ventilator and expiration to FRC, whereas blood gases were assessed only after that. Thus, an apnea-induced collapse of previously recruited lung units could explain the lack of effect of the RM on pulmonary gas exchange. As we did not assess blood gases during or immediately after the RM, we cannot draw any conclusions on the isolated effect of the maneuver on oxygenation.
We found a small but significant increase in the dEELV between tidal end-expiration and FRC after the RM, as compared with baseline. The post-maneuver measurements were done after 8 minutes of ventilation at a PEEP level of 5 cm H2O. More alveolar recruitment might have been present immediately after the RM, but because of the subsequent low level of PEEP, some degree of renewed collapse of lung units may have occurred over time. This may also have contributed to the lack of improved oxygenation.
In summary, a RM, performed in healthy animal lungs, produced a marked though transient impairment of total splanchnic, hepatic, splenic, renal, and carotid arterial as well as portal venous blood flows. Despite prompt partial recovery, total splanchnic, renal and portal blood flows remain reduced. This residual decrease may present a risk in conditions with markedly compromised circulatory reserves.
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© 2004 International Anesthesia Research Society
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