Positive End-expired Pressure Research Articles

Vagal Control of Breathing Pattern after Midcervical Contusion in Rats.

The present study was designed to establish a midcervical contusion model that can simulate long-term respiratory deficits, and investigate the breathing pattern during vagal-mediated respiratory reflexes following midcervical contusion. Moderate and severe (impactor height: 6.25 or 12.5 mm) contusion was induced at midline C3-4 spinal cord in adult Sprague-Dawley rats. The ventilatory behaviors of unanesthetized were evaluated by whole body plethysmography at 1 day and 1, 2, 4, and 8 weeks post-injury. The tidal volume was decreased and frequency was increased in contused animals compared with uninjured animals at the acute injury state. At 8 weeks post-injury, respiratory frequency was similar between groups; however, contused animals had lower tidal volume. The pulmonary chemoreflex induced by intrajugular capsaicin (1.5 μg/kg) injection and the Hering-Breuer inflation reflex induced by increasing positive end-expired pressure (9 cm H2O) were evoked in anesthetized animals at 3 days, or 2 or 8 weeks post-surgery. The result showed that capsaicin induced a significant prolongation of the expiratory duration in uninjured animals; however, this response was greatly attenuated in contused animals at 3 days post-injury. Increased positive end-expired pressure also caused an increase in the expiratory duration in uninjured and moderately contused animals; however, severely contused animals exhibited an attenuated response. At 2 and 8 weeks post-injury, both the pulmonary chemoreflex and the Hering-Breuer inflation reflex were similar between uninjured and contused animals. These data suggested that midcervical contusion can cause a long-term respiratory impairment and a transiently attenuation of vagal-mediated respiratory reflexes.

Board 505 - Technology Innovations Abstract Modification of the SimMan 3G Lung Mechanics Improves Performance During Critical Care Ventilation (Submission #1060)

Introduction/Background A key requirement of high-fidelity simulation is mechanical ventilation in critical care areas such as the intensive care unit. There is an unmet need to improve lung mechanics when using the SimMan 3G (Laerdal, Norway) patient simulator with modern critical care ventilators. Critical care ventilators are able to make use of a variety of complex ventilation modes (e.g., pressure control, volume control, pressure support) and incorporate positive end-expired pressure. We compared the SimMan 3G’s lung system with the lung mechanics of two other lung simulators that are sometimes used in conjunction with teaching critical care ventilation. We investigated how modifications to the lung system on the SimMan 3G would enable compatibility over a broad range of critical care ventilation modes. Methods We first compared the lung mechanics of the unmodified SimMan 3G with those of the Michigan Training and Test Lung (TTL, Michigan Instruments, Grand Rapids, MI), and the Siemens Lung Simulator. The Esprit ventilator (Philips Medical, Carlsbad, CA) was used to ventilate each of these lung simulation systems the Michigan TTL, SimMan 3G and the Siemens 920 for a variety of ventilation modes, tidal volumes, respiratory rates, and PEEP levels while the NICO® monitor (Philips, Wallingford, CT) recorded the lung mechanics parameters. Normal lung mechanics were defined as those observed with the Michigan TTL, set to have normal resistance (approximately 3 cm H2O l-1sec-1) and normal compliance (approximately 50 mL/cm H2O). We then made modifications to the SimMan® 3G by adding 650 grams of weight to the top of each lung plate and eliminating the elbow connectors on the small tubing between the chest walls and the lungs in order to slightly reduce airway resistance. We retested the modified lungs using the same ventilation modes. During volume controlled ventilation with normal tidal volume, compliance and resistance settings and zero PEEP, the unmodified SimMan 3G performs acceptably, though resistance is above normal and compliance is below normal. However, we observed high peak inspiratory and plateau pressures during many settings of critical care ventilation for the Siemens 920 and the SimMan® 3G which resulted in high pressure alarms from the ventilator. Large tidal volumes (> 700 mL) pose a challenge for both simulators, especially with PEEP > 0cm H2O. After modifications to the SimMan 3G lung were made, PEEP set to 0-10 cm H2O, tidal volume up to 1000 mL, and high inspiratory flow were compatible in most cases. Results: Conclusion We suggest that for critical care ventilation scenarios, the simulation experience can be improved for the SimMan 3G if 650 grams of weight is added to each of the lung plates and the elbow connectors on the small tubing between the chest walls and the lungs are removed. With these modifications, standard ventilation modes without the use of PEEP remains acceptable, albeit at slightly elevated pressures compared to the unaltered lungs. Our modifications and Results may compliment the prior work performed by other groups who made modifications to the SimMan 3G lung system.1

Influence of vagal afferents on supraspinal and spinal respiratory activity following cervical spinal cord injury in rats

C(2) spinal hemisection (C2HS) interrupts ipsilateral bulbospinal pathways and induces compensatory increases in contralateral spinal and possibly supraspinal respiratory output. Our first purpose was to test the hypothesis that after C2HS contralateral respiratory motor outputs become resistant to vagal inhibitory inputs associated with lung inflation. Bilateral phrenic and contralateral hypoglossal (XII) neurograms were recorded in anesthetized and ventilated rats. In uninjured (control) rats, lung inflation induced by positive end-expired pressure (PEEP; 3-9 cmH(2)O) robustly inhibited both phrenic and XII bursting. At 2 wk post-C2HS, PEEP evoked a complex response associated with phrenic bursts of both reduced and augmented amplitude, but with no overall change in the mean burst amplitude. PEEP-induced inhibition of XII bursting was still present but was attenuated relative to controls. However, by 8 wk post-C2HS PEEP-induced inhibition of both phrenic and XII output were similar to that in controls. Our second purpose was to test the hypothesis that vagal afferents inhibit ipsilateral phrenic bursting, thereby limiting the incidence of the spontaneous crossed phrenic phenomenon in vagal-intact rats. Bilateral vagotomy greatly enhanced ipsilateral phrenic bursting, which was either weak or absent in vagal-intact rats at both 2 and 8 wk post-C2HS. We conclude that 1) compensatory increases in contralateral phrenic and XII output after C2HS blunt the inhibitory influence of vagal afferents during lung inflation and 2) vagal afferents robustly inhibit ipsilateral phrenic bursting. These vagotomy data appear to explain the variability in the literature regarding the onset of the spontaneous crossed phrenic phenomenon in spontaneously breathing (vagal intact) vs. ventilated (vagotomized) preparations.

Pulmonary C-fiber receptor activation abolishes uncoupled facial nerve activity from phrenic bursting during positive end-expired pressure in the rat

Phasic respiratory bursting in the facial nerve (FN) can be uncoupled from phrenic bursting by application of 9 cmH(2)O positive end-expired pressure (PEEP). This response reflects excitation of expiratory-inspiratory (EI) and preinspiratory (Pre-I) facial neurons during the Pre-I period and inhibition of EI neurons during inspiration (I). Because activation of pulmonary C-fiber (PCF) receptors can inhibit the discharge of EI and Pre-I neurons, we hypothesized that PCF receptor activation via capsaicin would attenuate or abolish uncoupled FN bursting with an increase from 3 cmH(2)O (baseline) to 9 cmH(2)O PEEP. Neurograms were recorded in the FN and phrenic nerve in anesthetized, ventilated, vagally intact adult Wistar rats. Increasing PEEP to 9 cmH(2)O resulted in a persistent rhythmic discharge in the FN during phrenic quiescence (i.e., uncoupled bursting). Combination of PEEP with intrajugular capsaicin injection severely attenuated or eliminated uncoupled bursting in the FN (P < 0.05). Additional experiments examined the pattern of facial motoneuron (vs. neurogram) bursting during PEEP application and capsaicin treatment. These single-fiber recordings confirmed that Pre-I and EI (but not I) neurons continued to burst during PEEP-induced phrenic apnea. Capsaicin treatment during PEEP substantially inhibited Pre-I and EI neuron discharge. Finally, analyses of FN and motoneuron bursting across the respiratory cycle indicated that the inhibitory effects of capsaicin were more pronounced during the Pre-I period. We conclude that activation of PCF receptors can inhibit FN bursting during PEEP-induced phrenic apnea by inhibiting EI and I facial motoneuron discharge.

Inhibition of respiratory‐related activity of the facial nerve by pulmonary vagal C‐fiber activation in the rat

We have previously reported that respiratory-related facial nerve activity can be modulated by hypercapnia, lung inflation, and positive end-expired pressure (PEEP). Whether respiratory-related rhythmic activities of the facial nerve could be modulated by pulmonary C-fiber activation is unclear. Activity of the facial and phrenic nerve was recorded simultaneously in the anesthetized and ventilated adult rat. Activation pulmonary C-fiber by intra-jugular injection of capsaicin produced a dose-dependent reduction of amplitude and onset of the facial nerve activity. Furthermore, uncoupled facial activity (persistent rhythmic activity during phrenic cessation) evoked by increasing PEEP could be also suppressed by capsaicin injection. Single fiber recording from the facial nerve revealed that capsaicin treatment produced inhibition on activity of expiratory-inspiratory (EI) motoneuron during expiration such that became inspiratory motoneurons and of pre-inspiratory motoneurons. In addition, capsaicin injection could attenuate the uncoupled activity of EI from the phrenic burst caused by PEEP manipulation. These results implied that capsaicin might differentially inhibit pre-inspiratory than inspiratory facial activity.

Uncoupling of upper airway motor activity from phrenic bursting by positive end-expired pressure in the rat

Phasic bursting in the hypoglossal nerve can be uncoupled from phrenic bursting by application of positive end-expired pressure (PEEP). We wished to determine whether similar uncoupling can also be induced in other respiratory-modulated upper airway (UAW) motor outputs. Discharge of the facial, hypoglossal, superior laryngeal, recurrent laryngeal, and phrenic nerves was recorded in anesthetized, ventilated rats during stepwise changes in PEEP with a normocapnic, hyperoxic background. Application of 3- to 6-cmH(2)O PEEP caused the onset inspiratory (I) UAW nerve bursting to precede the phrenic burst but did not uncouple bursting. In contrast, application of 9- to 12-cmH(2)O PEEP uncoupled UAW neurograms such that rhythmic bursting occurred during periods of phrenic quiescence. Single-fiber recording experiments were conducted to determine whether a specific population of UAW motoneurons is recruited during uncoupled bursting. The data indicate that expiratory-inspiratory (EI) motoneurons remained active, while I motoneurons did not fire during uncoupled UAW bursting. Finally, we examined the relationship between motoneuron discharge rate and PEEP during coupled UAW and phrenic bursting. EI discharge rate was linearly related to PEEP during preinspiration, but showed no relationship to PEEP during inspiration. Our results demonstrate that multiple UAW motor outputs can be uncoupled from phrenic bursting, and this response is associated with bursting of EI nerve fibers. The relationship between PEEP and EI motoneuron discharge rate differs during preinspiratory and I periods; this may indicate that bursting during these phases of the respiratory cycle is controlled by distinct neuronal outputs.

Characteristics of pre‐inspiratory and decoupled activities of the upper airway motoneurons in the rat

Inspiratory activities of the upper airway motor nerves (UAWMN) commence before phrenic burst. These pre-inspiratory (Pre-I) activities of the UAWMN may play an important role in the stabilization of UAW patency. To get insight into the mechanism for this preceding onset of the UAW motoneurons, we investigated influence of different level of positive end-expired pressure (PEEP) on pre-I activities of UAWMN in the first part of the current study. Activities of UAWMN, including the facial, hypoglossal, and superior laryngeal nerves, and the phrenic nerve were recorded simultaneously in anesthetized and artificially ventilated rats. Our results showed that Pre-I activities of UAWMN were all increased and even decoupled from phrenic burst (a response activity during phrenic cessation) by the increase of PEEP to a level between 6–12 cmH2O. Further increased PEEP to a level of 15 cmH2O produced, however, an inhibition on Pre-I and decoupled activities. In the second part, we monitored single fiber activities on each of the UAWMN and found that decoupled activity was primarily due to the persistence of activities of expiratory-inspiratory (EI) motoneurons during phrenic burst cessation. Our data suggest that signals from changes in PEEP might induce either excitation or inhibition on Pre-I and decoupled activities of UAWMN. They might also indicate that rhythmic activities of UAWMN could be uncoupled from the phrenic nerve burst by increasing PEEP.

“Best” PEEP during one-lung ventilation

Eight patients were studied under general anaesthesia for elective pulmonary lobectomy to see if intrinsic positive end-expired pressure (PEEPi) would appear or increase in the dependent lung during one-lung ventilation (OLV) or if application of external PEEP equal to individually measured PEEPi would produce better arterial oxygenation, haemodynamic state and oxygen delivery than either zero PEEP (ZEEP) or an external PEEP 5 cm H2O greater than PEEPi. Patients were non-obese, without obstructive airways disease, aged 53-76 yr and ASA < III. They received standardized anaesthesia with fentanyl, 50% nitrous oxide in oxygen and isoflurane; monitoring included radial and fibreoptic pulmonary arterial catheters and intermittent positive pressure ventilation with a tidal volume of 8 ml kg-1, 16 bpm, and an I:E ratio of 1:2. PEEPi was measured during two-lung ventilation (TLV) and OLV, using rapid airway occlusion at end-expiration. There was no PEEPi during TLV, but 2-6 mm Hg of PEEPi appeared during OLV. Applying external PEEP equal to individually measured PEEPi reduced venous admixture and increased PaO2 without a decrease in cardiac index (thus increasing oxygen delivery) compared with ZEEP, but the improvement in pulmonary gas exchange was lost and an additional penalty of reduced cardiac output was imposed when external PEEP was increased to 5 mm Hg above PEEPi.

Clearance of 99mTc-labeled albumin from lungs in anesthetized guinea pigs.

Gamma imaging was used to measure the rate of clearance of aerosolized 99mTc-human serum albumin (HSA) from the lungs of control guinea pigs and guinea pigs that received increased lung inflation or lung injury. Anesthetized guinea pigs were ventilated for 6 min with an aerosol of HSA and the radioactivity in the chest was monitored for 2 h with a gamma camera to determine whether the clearance rate would be a reliable assessment of lung epithelial permeability. Increased lung volumes were effected by application of 5 or 7 cm H2O positive end-expired pressure (5-PEEP and 7-PEEP, respectively). Lung injury was induced either by intravenous oleic acid (OA, 27-73 microliters/kg) or inhalation of nitrogen dioxide (NO2, 80-100 ppm) for 2 h. Postmortem extravascular lung water volume (EVLW) provided an assessment of the degree of lung injury. Tracer clearance rates in animals receiving 5 or 7 cm H2O PEEP were not significantly different from controls (K = 0.15 +/- 0.05 and 0.24 +/- 0.10 vs 0.12 +/- 0.03%/min, respectively, p > .05). Animals exposed to NO2 had faster tracer clearance rates (K = 0.33 +/- 0.21%/min, p < .05) and higher EVLW (5.8 +/- 3.0 vs 3.7 +/- 0.2 mL/g dry lung, p < .05) than controls. Clearance rates of HSA from the lungs of NO2-exposed guinea pigs correlated well with injury as assessed by EVLW (r = .93, p < .01). Clearance rates of HSA and EVLW in animals receiving oleic acid were significantly higher than controls and the group receiving 5 cm H2O PEEP (K = 0.58 +/- 0.41%/min, EVLW = 8.1 +/- 0.8 mL/g dry lung tissue, p < .05), but there was no correlation between these parameters in this injury model. It is concluded that imaging of the disappearance of radiolabeled HSA in the guinea pig can be a useful index of lung epithelial permeability, but this technique is limited to certain models of lung injury.

Effect of Aerosol Size on the Clearance of DTPA from Lungs of Anesthetized Sheep

Aerosolized 99mTc–diethylenetriamine pentaacetate (DTPA) clears uniformly from the air spaces in control sheep. However, in response to increased lung volume due to a positive end expired pressure (PEEP) of 10 cmH20, a portion of the DTPA clears very rapidly (fast compartment) while the remainder clears at a normal rate. We tested the hypothesis that the fraction of DTPA that cleared rapidly from the lungs was proportional to the fraction that deposited in the alveoli. We performed a compartment analysis of the clearance of DTPA delivered to anesthetized sheep in 4 different size aerosols. When the DTPA was delivered in a 1.0 micron aerosol, 77 ± 7% of the DTPA cleared rapidly. This fraction decreased with increasing aerosol size with only 36 ± 14% of the DTPA clearing rapidly for the 6.8 micron aerosol. A postmortem analysis of the site of deposition of the aerosols confirmed that the 1.0 micron aerosol deposited primarily in the alveoli and small airways (<1 mm diameter) and the 6.8 micron aerosol deposited primarily in 7–8 mm airways. Therefore, the fast compartment in the clearance of DTPA from lungs ventilated with a PEEP of 10 cmH2O represents the fraction of the DTPA that deposited in the alveoli and small airways. This compartment analysis of the clearance rate may be useful as a noninvasive index of peripheral deposition of aerosols.

Minimal Positive End-Expiratory Pressure (PEEP) May be “Best PEEP”

In the absence of clinical trials, positive end-expired pressure (PEEP) has been accepted as efficacious for treatment of postoperative decreases in arterial oxygen tension (PaO2) from a variety of causes including adult respiratory distress syndrome (ARDS). PEEP is thought to increase PaO2 by alveolar recruitment, which in turn, has been hypothesized to play a decisive role in pulmonary recovery. One hundred and eighteen patients were followed prospectively, and after development of decreased PaO2, randomized to receive recruitive PEEP (determined by blood gas criteria) or supportive PEEP (the minimal PEEP required to maintain PaO2 above 60 mm Hg on .5 inspired O2 fraction (FIO2). No prognostic factors were significantly different between the two groups. Recruitive PEEP application in 22 patients yielded a significantly increased incidence of hypotension (55 percent), pneumothorax (20 percent), and death during treatment (27 percent) when compared to the 28 supportive PEEP patients who had no hypotension or pneumothorax and only one death during treatment (4 percent). After PEEP treatment, deaths in each group were similar (19 percent and 15 percent, respectively). We find no evidence that PEEP treatment promotes beneficial outcomes and conclude that recruitment attempts may be harmful.

Pulmonary lymphatic clearance of 99mTc-DTPA from air spaces during lung inflation and lung injury.

A total of 22 sheep with lymphatic cannulas were used to determine if 99mTc-labeled diethylenetriaminepentaacetic acid (DTPA) clears directly from the air spaces of the lungs into the lymph vessels. Each sheep was anesthetized and ventilated with an aerosol of the DTPA for 2-5 min, and the DTPA activities in the lymph and plasma were measured every 15 min for 2 h. After the first 45 min, the average ratio of the DTPA in the lymph to that in the plasma (L/P) was 1.03 +/- 0.06 (SD) in the six control experiments and 1.11 +/- 0.05 in the six experiments in which the lungs were inflated with a positive end-expired pressure of 10 cmH2O throughout the study. Direct movement of the DTPA from the air spaces into the lymph was not necessary to account for the DTPA clearance in these experiments because the L/P ratio was not significantly different from 1.0. Eight additional sheep received intravenous infusions of air at 0.2 ml.kg-1.min-1 for 2 h to induce lung injury before depositing the DTPA. In these sheep L/P was 1.53 +/- 0.28, which was significantly higher than the value measured in the control group (P less than 0.01). We considered the possibility that the increased L/P ratio in these sheep could be due to alterations in the distribution of the blood flow to the tissue, but the L/P ratio in four sheep whose distribution of blood flow was altered by inflation of a balloon in the right pulmonary artery was 1.05 +/- 0.10, the same as the control value.(ABSTRACT TRUNCATED AT 250 WORDS)

Dimensional analysis of right and left ventricles during positive-pressure ventilation in dogs.

Our purpose was to determine the effects of controlled ventilation with positive end-expired pressure (PEEP) on ventricular dimensions and to relate changes in shape to changes in stroke volume and left ventricular volumes. Left and right ventricular dimensions were measured using biplane cinefluorography of dogs with radiopaque markers implanted in their hearts, and left ventricular volumes were derived from left ventricular dimensions by assuming that the left ventricle conformed to the shape of a nonprolate ellipsoid. As PEEP increased from 0 to 5, 10, and 15 cmH2O, stroke volume fell 36%, and all three left ventricular end-diastolic dimensions fell, with apex-base falling 5%, anterior-posterior falling 7%, and septal-lateral falling nearly twice as much, 12%. This resulted in a 11.3 cm3 fall in left ventricular end-diastolic volume. The right ventricular end-diastolic dimensions changed in opposite directions with respect to each other as the level and PEEP was raised to 15 cmH2O; one axis fell 3.2 mm, and the midpoint of the right ventricular free wall moved outward by 1.7 mm. Thus the fall in cardiac output (and stroke volume) during PEEP was associated with a fall in left ventricular end-diastolic volume and a change both left and right ventricular configurations. It is not known whether the left ventricular septal-lateral narrowing is the consequence of lateral wall compression by the lungs or encroachment on the left ventricle by the septum.

Location of lung receptors mediating the breathing frequency response to pulmonary CO 2

Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO 2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO 2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO 2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO 2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO 2 response are located in the more peripheral regions of the lung.

The effect of positive end-expiratory pressure (PEEP) ventilation in neurogenic pulmonary oedema

The effect of positive end-expired pressure ventilation (PEEP) on mean systemic arterial pressure, mean pulmonary arterial pressure, mean pulmonary wedge pressure, mean intracranial pressure (ICP), and cerebral perfusion pressure (CPP), in a case of neurogenic pulmonary oedema (NPO) is presented. PEEP improved oxygenation, reduced, and finally stopped clinical pulmonary oedema. In this patient PEEP produced severe systemic hypotension. As a consequence of this, CPP was impaired.