Intermittent CPAP : A New Mode of Ventilation during General Anesthesia

We studied patients classified as physical status 1 and 2 of the American Society of Anesthesiologists who were scheduled for general anesthesia, intraabdominal operation, and insertion of an intraarterial catheter to monitor blood pressure. All patients signed a consent form approved by the Institutional Review Board. Excluded were patients who had unstable cardiovascular function or severe obstructive lung disease. Chest leads II and V5 were attached for electrocardiographic monitoring, and heart rate was determined electronically. A probe placed on a finger tip allowed oxygen saturation to be measured by pulse oximetry.

Anesthesia and neuromuscular blockade were induced with propofol (1 or 2 mg/kg administered intravenously), or thiopental (2–5 mg/kg administered intravenously) and succinylcholine (1.5 mg/kg administered intravenously), respectively. Anesthesia and neuromuscular blockade were maintained with isoflurane, nitrous oxide, and oxygen or with vecuronium, respectively. All patients were orotracheally intubated. Patients initially were ventilated with CMV using a VT of 8–10 ml/kg and a respiratory rate sufficient to keep PET^CO2between 30 and 35 mmHg. The fractional concentration of inspired oxygen (FI^O2) was adjusted to keep the Sp (^O)²at 90% or higher. A thermistor placed in the esophagus monitored temperature. A catheter inserted into the radial artery permitted determination of blood pressure, pHa, Pa^CO2, Pa^O2, hemoglobin concentration, and oxyhemoglobin saturation. A flow transducer (VarFlex; Allied Healthcare Products, Irvine, CA) attached to the tracheal tube was connected to a pulmonary mechanics computer (BICORE CP-100; Allied Healthcare Products) to determine VT, respiratory rate, minute ventilation (VE), peak inspiratory gas flow rate, and peak and mean airway pressures. The pulmonary mechanics monitor is factory calibrated with room air (oral communication, Larry Butcher, Allied Healthcare Engineering Department, 1996), so that volumes calculated during general anesthesia necessitated correction for nitrous oxide and isoflurane. Using a calibrated 1–1 super syringe (Hamilton Medical Corp., Reno, NV), identical volumes of room air and a gas mixture identical to that breathed by the patient were injected through the pneumotachograph. The resulting ratio (volume air:volume anesthetic gas mixture) was used to correct the respired gas volumes obtained from the computer during the investigation. The sample tubing of a gas and anesthetic vapor monitor (Ultima; Datex-Engstrom, Helsinki, Finland) was positioned between the pneumotachograph and the anesthesia breathing circuit to determine the fractional concentration of inspired oxygen, PET^CO2, and the end-tidal concentrations of isoflurane and nitrous oxide. Baseline data were collected after the abdominal incision was made, and heart rate, mean arterial blood pressure, and end-expired concentration of isoflurane remained unchanged for 30 min. We assumed relatively constant Pa^CO2and carbon dioxide production, and we quantified the efficiency of ventilation by calculating Pa^CO2/VE(the normal value is approximately 7.4 mmHg [middle dot] 1^-1[middle dot] min^-1for awake humans).

Patients were assigned randomly to receive alternating 20-min trials of CMV (using the same characteristics as baseline) and CPAPI. To provide CPAPI, we used a modified ventilator (model Mark 4A; Bird Corp., Palm Springs, CA). Alveolar ventilation is produced by intermittent release of CPAP nearly to atmospheric pressure (Figure 1). After a release period is 1 s, CPAP is restored and lung volume is reestablished. The respiratory rate during CPAPI was the same as during baseline CMV. However, because previous investigations revealed that dead-space ventilation was lower during APRV than during CMV, during CPAPI [1,6]the desired tidal volume was obtained by titration of CPAP to produce a PET^CO2that was 2 or 3 mmHg more than the value observed during baseline CMV; this was performed to try to produce equivalent alveolar ventilation and Pa^CO2.

Data are summarized as mean +/- 1 SD. To assess the possibility of a carry over of treatment effect (treatment - period interaction), we compared the differences (mean +/- 1 SD) for the two treatment sequences. [9]To compare the differences between the two treatment sequences, we applied the Student's t test for independent observations. There was no significant treatment - period interaction, therefore, data were compared statistically using the Student's t test for paired observations (two tailed). We used regression analysis to assess the mathematical relation between PET^CO2and Pa^CO2. We tested the null hypothesis that the two regressions were coincident (i.e., they have the same slope and intercept) according to the technique described by Glantz. [10]We also quantified the strength of the association between PET^CO2and Pa (^CO)²by calculating Pearson's product-moment correlation (r). We tested the null hypothesis that the two correlations were the same according to a technique described by Zar. [11] 

Twenty patients (11 women, 9 men) who were 62 +/- 15 yr old and who weighed 88 +/- 26 kg underwent similar anesthesia care and operative procedures. The end-tidal concentration of isoflurane (1.1 +/- 0.3%), body temperature (35.7%+/- 0.5 [degree sign]C), and hemoglobin concentration (10.8 +/- 1.5 g/dl) were similar throughout the study, and intertrial data were pooled for summary. There were no differences in variables reflecting cardio-vascular function throughout the study (Table 1).

Peak airway pressure was less during CPAPI than during CMV (Table 2). During CPAPI, peak airway pressure did not exceed 18 cm H²O in any patient, and in six patients, it was less than one half that observed during CMV. Although mean airway pressure was higher during CPAPI, no adverse cardiovascular consequences were apparent. During CMV, peak inspiratory gas flow rate was 0.7 +/- 0.2 1/min. After interruption of CPAP during CPAPI, a peak flow of 1.3 +/- 0.4 l/min restored the CPAP level. The respiratory rate was similar by design, but during CPAPI, comparable Pa^CO2was achieved with less tidal volume and minute ventilation. Thus CPAPI improved the efficiency of ventilation, as quantified by a higher value for Pa^CO(^2/VE)(Table 3).

There were no differences in the fractional concentration of inspired oxygen, and arterial blood gas tensions, pHa, and oxyhemoglobin saturation did not change during the study. The correlation coefficient between Pa^CO2and PET^CO2was closer to unity for CPAPI (r = 0.95) than for CMV (r = 0.80; P < 0.10;Figure 2). There was a significant difference in the lines of least squares resulting from the regression of PET^CO2on Pa^CO2during CMV versus CPAPI (P < 0.001). The slope of the regression ([small beta, Greek]) of PET^CO2on Pa^CO2was closer to 1 during CPAPI ([small beta, Greek]= 0.90) than during CMV ([small beta, Greek]= 0.62). The y-axis intercept ([small alpha, Greek]) was 2.43 during CPAPI and 9.07 during CMV. The arterial-to-end-tidal carbon dioxide partial pressure difference [P(a - ET)^CO2] was always less during CPAPI (1.7 +/- 0.9 mmHg) than during CMV (6.3 +/- 1.6 mmHg; P < 0.0001) and was never more than 3.5 mmHg during CPAPI. During CMV, P(a - ET)^CO2ranged from 4 to 10 mmHg.

We designed and tried to evaluate CPAPI as a ventilatory support technique for patients undergoing general anesthesia and neuromuscular blockade. We observed that the minute ventilation necessary to achieve similar alveolar ventilation, as reflected by Pa^CO2, was less when patients were ventilated with CPAPI versus CMV. Normal awake VT is approximately 6 ml/kg. Our results indicate that such a VT provided by CPAPI at a rate of 7/min will produce a normal Pa^CO2. Because anatomic dead space was presumed to be nearly constant, the ability to achieve comparable Pa^CO2with a lower P(a - ET)^CO2and a lesser minute ventilation was evidence of less alveolar dead-space ventilation during CPAPI. The reduction in alveolar dead space ventilation rendered PET (^CO)²a more accurate reflection of Pa^CO2during CPAPI than during CMV. The observation that dead-space ventilation is lower also has been commonly noted during APRV. This finding may be explained by the similarly low peak airway pressure during CPAPI and APRV. [1,2,6]Although mean airway pressure was higher during our trials of CPAPI, no adverse cardiovascular consequences seemed to occur.

The following Equation providesan estimate of the amount of change (Delta) in functional residual capacity (FRC) effected by CPAP:

Delta FRC = CPAP x Clt

where Clt is lung-thorax compliance. [12]Periodic release of CPAP causes lung volume to decrease, and restoration of CPAP causes lung volume to increase, thus providing alveolar ventilation and excretion of carbon dioxide. [13] 

Airway pressure - release ventilation provides adequate alveolar ventilation in anesthetized experimental animals with healthy and injured lungs and in patients with mild to severe acute lung injury. Fundamentally, APRV differs from other methods of positive pressure ventilation in that it is a CPAP system designed to increase resting lung volume and to augment alveolar ventilation, when spontaneous ventilation is inadequate. Several factors determine the VT produced by APRV: release time, release pressure, airway resistance, and lung-thorax compliance. The time necessary for gas to leave the lung during pressure release is determined by CLT and the resistance to gas flow. The product of these variables is the time constant for exhalation, and, as long as the release time exceeds three time constants, the VT is the product of CLT and the release pressure. [4]Because all of these principles also apply to CPAPI, it may be possible to monitor respiratory mechanics continuously during CPAPI in anesthetized patients.

Positive-pressure inflation of the lungs can cause adverse cardiovascular effects. We found no differences in cardiovascular function during CPAPI and CMV, which probably was caused by the low mean airway pressure observed with both modes. Previous investigations have reported adverse cardiovascular sequelae that occurred with intermittent positive-pressure ventilation, but not with APRV. [1,2]Because APRV provides mechanical ventilation by decreasing airway pressure from a level of CPAP titrated to optimize lung mechanics, peak airway pressure never exceeds CPAP, and mean airway pressure is less than the CPAP level. Therefore, the lack of adverse pressure-related effects is not surprising.

The value for P(a - ET)^CO2during CPAPI was similar to that observed in spontaneously breathing patients. [14]During spontaneous breathing, inspired gas is distributed predominately to relatively well-perfused alveoli in dependent lung regions, and the end-expired gas closely approximates alveolar gas. However, in anesthetized, paralyzed, and mechanically ventilated patients, the inspired gas is distributed preferentially to poorly perfused or nonperfused alveoli in nondependent lung units, and the end-expired gas contains a significant contribution from alveolar dead space. [15–18]During normal spontaneous breathing, P(a - ET)^CO2may range from 1 to 3 mmHg. [14]During CMV, P(a - ET)(^CO)²may exceed 12 mmHg and is rarely < 6 mmHg. [18]When mechanical inspiration occurs from a lung volume less than normal FRC, the maldistribution of inspired air relative to perfusion is exaggerated. [19]Thus, alveolar dead-space ventilation is greater during CMV, particularly when FRC decreases, as occurs immediately after induction of general anesthesia.

Valentine et al. [6]observed a distribution of less ventilation to nonperfused alveoli (dead space) with similar tidal volume and frequency during APRV than during intermittent mandatory ventilation and pressure support ventilation. Although we did not quantify dead space, the improved efficiency of ventilation during CPAPI versus CMV, as evidenced by a higher value for Pa^CO2/VE, indicates that alveolar dead-space ventilation was less during CPAPI. As noted in Figure 2, the slope and intercept of the least-squares regression lines for PET^CO2versus Pa^CO2are different for CMV and CPAPI. Furthermore, the slope of the least-squares regression line for PET^CO2versus Pa^CO2obtained during CPAPI was 0.90 and the y-axis intercept was 2.43 mmHg, indicating that PET^CO2closely reflects Pa^CO2, regardless of the Pa^CO2value. In contrast, with higher values of Pa^CO(²) observed during CMV, P(a - ET)^CO2increased, secondary to increased alveolar dead space, rendering PET^CO2a progressively less accurate monitor of Pa^CO2. Presumably, lower peak airway pressure during CPAPI caused less alveolar dead space in nondependent lung regions.

Intermittent CPAP; pressure-controlled, inverse ratio ventilation; and APRV share several common characteristics, but conceptually they are quite different. Pressure-controlled, inverse ratio ventilation is applied to critically ill patients with severe respiratory dysfunction, usually with an elevated end-expiratory pressure. Spontaneous breathing is not possible and extreme sedation, muscle relaxation, or both, usually are administered. A pressure limit is selected to produce acceptable VT and peak positive airway pressures. As the patient's condition improves, pressure-controlled, inverse ratio ventilation gradually is discontinued by decreasing inspiratory time and mean positive airway pressure.

Airway pressure - release ventilation is applied to spontaneously breathing patients with a restrictive ventilatory defect to optimize FRC with CPAP. If necessary, the CPAP level is decreased briefly (usually 1 s or less) to allow a decrease in lung volume and carbon dioxide excretion. As the patient's condition improves, and he or she is more able to breathe, the rate of release is decreased and mean airway pressure increases.

During general anesthesia, CPAPI is applied to a level that will produce a desirable VT when removed. Then the CPAP is reduced intermittently to produce ventilation; there is no intent to “restore” normal FRC, to optimize lung mechanics, or to improve oxygenation. Then, CPAPI can be discontinued at the end of the anesthetic. Although the airway pressure patterns may be similar, pressure-controlled, inverse ratio ventilation; APRV; and CPAPI are distinctly different in concept, application, and mode of discontinuation.

Because our patients received continuous neuromuscular blockade, CMV and CPAPI both provided total ventilatory support. Existing methods do not permit application of partial ventilatory support techniques, such as intermittent mandatory ventilation or APRV, during anesthesia. However, the use of CPAPI to provide partial mechanical support of spontaneously breathing patients who cannot maintain an acceptable Pa^CO2during general anesthesia may have several advantages over the use of CMV:(1) lower mean intrathoracic (pleural) pressure;(2) augmented venous return and improved cardiovascular performance; and (3) better distribution of inspired gas, resulting in improved matching of ventilation and perfusion. All of these advantages occur when APRV is used to provide partial ventilatory support in awake humans. [8]The role for CPAPI in partial ventilatory support during general anesthesia should be evaluated.

Our results indicate that CPAPI provides more efficient ventilation of patients undergoing general anesthesia, with a significantly lower peak airway pressure compared with CMV. An improved efficiency of ventilation decreases the necessary minute ventilation and permits reduction of V^T, respiratory rate, or both, thus reducing the magnitude or frequency, respectively, of lung inflation. Thus, there is less respiratory movement and possible improvement in technical conditions during intraabdominal operations. During CPAPI, P(a - ET)^CO2approximates the value observed during spontaneous breathing, rendering PET^CO2a more accurate monitor of ventilation during CPAPI than during CMV.

Intermittent CPAP is a unique way to provide ventilatory support to anesthetized patients. It may have significant advantages with regard to gas exchange, efficiency of ventilation, and hemodynamic stability. Future investigations will determine the usefulness of CPAPI in clinical practice.