Donna F. Howland

Cardiac output during liquid (perfluorocarbon) breathing in newborn piglets

Background and MethodsLiquid ventilation using perfluorocarbons is a new technique for ventilation of infants with restrictive lung disease. However, this method of ventilation has been shown to impair cardiac output (&OV0422;t) in several animal species, casting doubt as to its feasibility. This study tested whether &OV0422;t could be maintained during liquid breathing by intravascular volume expansion. Seven piglets were carefully hydrated, instrumented for continuous &OV0422;t measurement, and subjected to 2 hr of liquid breathing. Paco2 was maintained at 40 to 50 torr (5.3 to 6.7 kPa), and Pao2 >80 torr (>10.7 kPa). Additional colloid was given during liquid breathing if &OV0422;t decreased to <90% of preliquid breathing values. ResultsFour piglets maintained &OV0422;t throughout the liquid breathing trial with maintenance fluids only. Three piglets each required one 10 mL/kg fluid bolus for &OV0422;t 82% to 89% of the baseline value, after which &OV0422;t rapidly increased to >90% of baseline. Oxygen consumption and serum lactate levels remained normal throughout liquid breathing. Conclusion&OV0422;t is readily maintained during liquid breathing in properly hydrated animals. (Crit Care Med 1991; 19:225)

Proximal mean airway pressure: a good estimator of mean alveolar pressure during continuous positive-pressure breathing.

Although airway and alveolar pressures are not instantly equal during positive-pressure ventilation, proximal mean airway pressure (Paw) is the simplest available indirect gauge of mean alveolar pressure (Palv). To ascertain the relation of Paw to Palv and the limits of agreement between the two measures, real-time curves of proximal airway pressure (at the hub of the endotracheal tube) and alveolar pressure were generated by repeated airway occlusion at numerous PEEP levels in four groups of ventilated lambs or piglets: normal controls, oleic acid-injured and serotonin stimulated lambs, and preparations with mechanically induced air trapping. From these curves, Paw and Palv were determined. In all groups, Paw proved to be a precise estimator of Palv during volume-regulated, time-cycled, continuous positive-pressure breathing.

Validity of a disposable end-tidal carbon dioxide detector in verifying endotracheal tube position in piglets

Background and MethodsThe most reliable methods for confirming endotracheal tube placement are direct visualization of passage through the vocal cords and documentation of CO2 in the expired gas. We evaluated the use of a disposable colorimetric CO2 detector for verifying endotracheal tube position in small animals.The end-tidal CO2 (Petco2) detector was tested in 11 piglets with the endotracheal tube sequentially in the trachea, the esophagus, the esophagus with a carbonated beverage in the stomach, the esophagus after bag-mask ventilation, and the trachea after bag-mask ventilation. Endotracheal tube position was confirmed in all cases by direct visualization and capnometry. ResultsThe Petco2 detector identified the tube placement accurately in all 54 (21 tracheal, 33 esophageal) intubations (p < .001). ConclusionsThis disposable Petco2 detector is highly sensitive and specific for verifying endotracheal tube placement in this nonarrest piglet model. (Crit Care Med 1991; 19:566)

Positive end-expiratory pressure-induced, calcium-channel-mediated increases in pulmonary vascular resistance in neonatal lambs.

Objectivesa) To study the dose response of the calcium-channel-mediated increases in pulmonary vascular resistance with different levels of positive end-expiratory pressure; b) to study the reversibility of the calcium-channel mediated increases in pulmonary vascular resistance after discontinuation of positive end-expiratory pressure; and c) to study the effect of cyclooxygenase and lipoxygenase inhibition on the calcium-channel mediated increases in pulmonary vascular resistance. DesignA prospective, multiexperimental, dose response study. SettingLaboratory setting in a university hospital. SubjectsTwenty-three 4− to 10-day-old neonatal lambs. Interventions and MeasurementsLungs of neonatal lambs were isolated in situ, and perfused at a constant flow rate, and ventilated at a fixed tidal volume and rate. Mean pulmonary arterial pressure responses to the application and discontinuation of four levels (3.7, 7.4, 11, and 14.7 mm Hg) of positive end-expiratory pressure were studied before and after calcium-channel blockade with verapamil (5 mg) (n = 12). In addition, the mean pulmonary arterial pressure response to 11 mm Hg of positive end-expiratory pressure was studied before and after inhibition of cyclooxygenase with indo-methacin (10 mg/kg) (n = 6) and lipoxygenase with diethylcarbamazine (100 mg/kg) (n = 5). ResultsThe magnitude of the calcium-channel-dependent mean pulmonary arterial pressure response 4 mins after the application of positive end-expiratory pressure was dose related (2.1, 3.0,4.1, and 5.5 mm Hg with 3.7,7.4, 11.0, and 14.7 mmHg positive end-expiratory pressure, respectively) and entirely reversible on discontinuation of positive end-expiratory pressure with a time course of 2 to 4 mins. Neither indomethacin nor diethylcarbamazine affected the pulmonary arterial pressure responses to positive end-expiratory pressure. Airway pressure changes with positive end-expiratory pressure were not affected by verapamil indomethacin, or diethylcarbamazine. ConclusionsThe calcium-channel-mediated pulmonary arterial pressure responses with positive end-expiratory pressure, applied during continuous positive pressure breathing, occur even at low levels of positive end-expiratory pressure, are dose dependent, and are not abolished by treatment with indomethacin or diethylcarbamazine.

Air Trapping Causes a Ca2+-Channel-Mediated Increase in Pulmonary Vascular Resistance in Neonatal Lambs

ABSTRACT: Air trapping and alveolar hyperinflation may occur during mechanical ventilation in the presence of severe airway obstruction, during fast ventilator rates, and when expiratory time is compromised. Inadvertent positive end-expiratory pressure may occur with air trapping and increased mean airway pressure. The pulmonary artery pressure response to air trapping, produced during volume-regulated time-cycled ventilation, was studied in neonatal lamb lungs, isolated in situ, and perfused at a constant flow rate (50–75 ml·kg-1·min-1), both before and after Ca2+-channel blockade with verapamil (5 mg). The hub of the endotracheal tube was narrowed to a 1.5-mm orifice to produce fixed proximal airway obstruction. Air trapping was then produced by lengthening inspiratory time from 25 to 80%, at zero end-expiratory pressure. The magnitude of inadvertent positive end-expiratory pressure due to air trapping was estimated by end-expiratory occlusion pressure. End-expiratory occlusion pressure was 0.20 ± 0.03 kPa (1.7 ± 0.2 mm Hg) and 1.60 ± 0.01 kPa (11.8 ± 1.0 mm Hg), at 25 and 80% inspiratory times, respectively. On lengthening inspiratory time, mean pulmonary artery pressure (mPpa) increased briskly within 30 s followed by a gradual increase over the next 4 min. Verapamil blunted both the brisk and the gradual increase in mPpa on lengthening inspiratory time. Lengthening inspiratory time increased the mPpa by 2.0 ± 0.1 kPa (14.7 ± 0.8 mm Hg) from baseline, and verapamil reduced this increase to 1.3 ± 0.1 kPa (10.1 ± 0.6 mm Hg; p < 0.05 by analysis of variance). Verapamil did not affect changes in mean airway and peak inspiratory airway pressures and the magnitude of inadvertent positive end-expiratory pressure caused by lengthening inspiratory time. In the neonatal lamb, the Ca2+-channel-dependent portion of the mPpa response to air trapping amplifies the Ca2+-channel-independent portion, which represents the compressive effects of airway pressure on the pulmonary circulation.

LEUKOTRIENE|[lpar]|LT|[rpar]|BLOCKERS AND THE PULMONARY CIRCULATION

LTs have been implicated in mediating hypoxic pulmonary vasoconstriction.We studied the LT blocker FPL 57231(FPL)in the pulmonary and systemic circulation in awake lambs. Flow probes were placed around the pulmonary arteries(PA)of six,3-7 day old lambs; a left atrial(LA) line was also placed. Catheters were placed in the aorta(Ao)and PA 7-14 days later. With the lambs awake, PA,Ao, and LA pressures(P;mmHg)and cardiac output(CO;ml/min) were measured in normoxia(N)and after 10 min. of hypoxia(H;fiO2=.11). A continuous infusion of FPL(2 mg/kg/min.)was begun during H, and hemodynamics recorded for 15 min. The FPL was then stopped, H maintained for 45 min., and hemodynamic measurements continued. By 15 min. after the start of the FPL,PAP returned to N level,and it fell further with continued FPL.AoP also fell,but less: after 15 min. of FPL, PAP fell 50%,AoP fell 23%.After FPL was stopped, PAP and AoP returned to nearly pre-FPL levels within 45 min.Propranolol(n=4;1 mg/kg)did not block the fall in PAP with FPL.These data support the notion that LTs contribute to hypoxic pulmonary vasoconstriction, and suggest that LT blockers may be useful in the treatment of pulmonary hypertension.

NEONATAL PULMONARY VASCULTURE: RECOVERY FROM POSITIVE END—EXPIRATORY PRESSURE (PEEP) IN IMPACT AND ISOLATED LUNGS

Unilateral PEEP (UPEEP) reduces ipsilateral pulmonary blood flow (PBF) in the intact (INT) newborn lamb. On cessation of UPEEP, ipsilateral PBF returns slowly to baseline. Intact and isolated lungs of 9 infant lambs were studied to examine the mechanism of this vascular hysteresis.Flow probes were placed on R and L pumonary arteries (PA) of 4 infant lambs. R and L lungs were intubated endobronchially and synchronously ventilated (Siemens-Elena Servo 900C). UPEEP was applied to the L lung for 4 min, abruptly discontinued and recovery of L lung blood flow (LPBF) followed for 4 min (11 trials). LPA was then occluded (LOC) for 4 min using a balloon catheter and recovery of LPBF on deflation followed for 4 min (11 trials). Recovery of PA pressure (P) after stopping PEEP was studied in 5 infant lambs after median sternotomy. Isolated in situ perfused lungs (ISO) were prepared; pulmonary vasculature paralysed; and recovery of PAP on cessation of PEEP studied.In the INT, on cessation of UPEEP, airway and vascular pressures, lung volumes, and RPBF returned to baseline within 10 sec but LPBF recovered slowly. LPBF returned promptly to baseline after balloon deflation and PAP recovered promptly after stopping PEEP in ISO after paralysis of pulmonary vasomotion. These data suggest that lung distension has a direct effect on pulmonary vascular tone in the intact infant lamb.

SEVERE AIRWAY OBSTRUCTION: AIRMY AND ALVEOLAR PRESSURES DURING CONTINUOUS POSITIVE PRESSURE BREATHING (CPPB)

During CPPB with severe airway obstruction end-expiratory occlusion pressure may exceed applied PEEP (autopeep). Alveolar pressure may then exceed airway pressure throughout expiration. This study examined the relationship of mean airway (PAW) and alveolar (PALV) pressures in the presence of “autopeep”.5 piglets (1-4kg) and 2 lambs (4-5kg) were ventilated with endotracheal tubes obstructed at the hub to an orifice of 1.5 mm. Alveolar pressure was estimated by repeatedly occluding the airway at times in the respiratory cycle that varied from trial to trial. Real time curves were reconstructed using occlusion time, proximal airway pressure and plateau occlusion pressure. PAW and PALV were estimated by integration of real time curves generated for inspiratory times (I) of 25% and 80% at levels of PEEP from 0 to 12 mmHg.Long I generated autopeep and, for any PEEP applied, increased both PAW and PALV. PAW remained an excellent predictor of PALV in spite of autopeep.

180 AIRWAY AND ALVEOLAR PRESSURES IN VENTILATED, ABNORMAL LUNGS

To describe the relations, during mechanical ventilation(CPPB), of airway pressure(AP) and its mean value(MAP) to alveolar pressure(ALP) and its mean value(MALP) in the diseased lung, 19 infant lambs were subjected to controlled, volume regulated CPPB at inspiratory(I) times of 25 and 50%, and at 0 to 11mmHg positive end-expiratory pressure(PEEP), under conditions of fixed inspiratory airflow. To estimate ALP, static recoil pressure was determined by airway occlusion once every 10th breath, at a time in the respiratory cycle that was varied from trial to trial. From measured occlusion times, AP and ALP, real time AP and ALP curves were generated representing one respiratory cycle; MAP and MALP were calculated by integration; and the contribution to MALP of airway resistance (MALPr) was estimated from %I, PEEP, peak ALP and MALP. After control determinations, 10 lambs received oleic acid (OA-.15 ml/kg) and 9 received propranalol and serotonin(S)all pressures mmHg, x±sem, †p<.05 vs control *p<.01 vs control Both OA and S increased airway resistance (Raw) and reduced both thoracic compliance(Ct) and arterial pO2. Proximal mean airway pressure was an accurate and precise estimator of mean alveolar pressure both in normal and in abnormal lungs, in spite of elevated airway, resistance.

179 PROXIMAL AIRWAY AND AVEOLAR PRESSURES DURING MECHANICAL VENTILATION

During continuous positive pressure breathing(CPPB), proximal airway pressure(AP) and its mean value(MAP) reflect lung distending pressure, although their relationships to alveolar pressure (ALP) and its mean value(MALP) await definition. 10 infant lambs, under chloralose anesthesia and pancuronium bromide, were subjected to volume regulated, time cycled CPPB under conditions of constant inspiratory airflow. To estimate ALP, static recoil pressure was determined by interruption of airflow once every 10th breath, at a time in the respiratory cycle that was varied from trial to trial. From determinations of occlusion time, AP and ALP, real time AP and ALP curves were generated representing one respiratory cycle; MAP and MALP were calculated by integration; and the contribution to MALP of airway resistance(MALPr) was estimated from inspiratory(I) time, positive end-expiratory pressure(PEEP), peak ALP and MALP. Curves were generated at 25 and 50%, I, and at levels of PEEP between 0 and 11 mmHg.Due to airway resistance, AP exceeded ALP in inspiration and ALP exceeded AP over much of expiration(E). Yet airway resistance contributed little to MALP. Over the range of PEEP applied, and at both %I, proximal mean airway pressure was an accurate and precise estimator of mean alveolar pressure.