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Current methods of forcing end-tidal PCO2 (PETCO2) and PO2 (PETO2) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control PETCO2 and PETO2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change PETCO2 from control (40 mmHg for PETCO2 and 100 mmHg for PETO2) to two target PETCO2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), PETO2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and PETCO2 with PETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, PETCO2 and PETO2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for PETCO2 was ± 1 mmHg, and for PETO2 was ± 4 mmHg. PETCO2 varied by ± 1 mmHg and PETO2 by ± 5.6 mmHg (s.d.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (± 7.6 l min−1). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.

We have previously shown that raising arterial Pco 2 (PaCO2 ) by small increments in dogs ventilated below the apneic threshold (AT) results in almost complete tracheal constriction before the return of phrenic activity (Dickstein JA, Greenberg A, Kruger J, Robicsek A, Silverman J, Sommer L, Sommer D, Volgyesi G, Iscoe S, and Fisher JA. J Appl Physiol 81: 1844–1849, 1996). We hypothesized that, if increasing chemical drive above the AT mediates increasing constrictor drive to tracheal smooth muscle, then pulmonary slowly adapting receptor input should elicit more tracheal dilation below the AT than above. In six methohexital sodium-anesthetized, paralyzed, and ventilated dogs, we measured changes in tracheal diameter in response to step increases in tidal volume (Vt) or respiratory frequency (f) below and above the AT at constant PaCO2 (∼40 and 67 Torr, respectively). Increases in Vt(400–1,200 ml) caused significantly more ( P = 0.005) tracheal dilation below than above AT (7.0 ± 2.2 vs. 2.8 ± 1.0 mm, respectively). In contrast, increases in f (14–22 breaths/min) caused similar ( P = 0.93) tracheal dilations below and above (1.0 ± 1.3 and 1.0 ± 0.8 mm, respectively) AT. The greater effectiveness of dilator stimuli below compared with above the AT is consistent with the hypothesis that drive to tracheal smooth muscle increases even after attainment of maximal constriction. Our results emphasize the importance of controlling Pco 2 with respect to the AT when tracheal smooth muscle tone is experimentally altered.

Researchers investigating the genetic component of various disease states rely increasingly on murine models. We have developed a ventilator to simplify respiratory research in small animals down to murine size. The new ventilator provides constant-flow inflation and tidal volume delivery independent of respiratory parameter changes. The inclusion of end-inspiratory and end-expiratory pauses simplifies the measurement of airway resistance and compliance and allows the detection of dynamic hyperinflation (auto-positive end-expiratory pressure). After bench testing, we performed intravenous methacholine challenge on two strains of mice (A/J and C57bl/bj) known to differ in their responses by using the new ventilator. Dynamic hyperinflation and a decrease in compliance developed during methacholine challenge whenever respiratory rates of 60–120 breaths/min were employed. In contrast, if dynamic hyperinflation was prevented by lengthening expiratory time, (respiratory rate = 20 breaths/min), static compliance remained constant. More importantly, the coefficient of variation of the results decreased when lung volume shifts were prevented. In conclusion, airway challenge studies have greater precision when dynamic hyperinflation is prevented.

A major impediment to the use of hyperpnea in the treatment of CO poisoning is the development of hypocapnia or discomfort of CO2 inhalation. We examined the effect of nonrebreathing isocapnic hyperpnea on the rate of decrease of carboxyhemoglobin levels (COHb) in five pentobarbital-anesthetized ventilated dogs first exposed to CO and then ventilated with room air at normocapnia (control). They were then ventilated with 100% O2 at control ventilation, and at six times control ventilation without hypocapnia ("isocapnic hyperpnea") for at least 42 min at each ventilator setting. We measured blood gases and COHb. At control ventilation, the half-time for elimination of COHb (t1/2) was 212 +/- 17 min (mean +/- SD) on room air and 42 +/- 3 min on 100% O2. The t1/2 decreased to 18 +/- 2 min (p < 0.0005) during isocapnic hyperpnea. In two similarly prepared dogs treated with hyperbaric O2, the t1/2 were 20 and 28 min. We conclude that isocapnic hyperpnea more than doubles the rate of COHb elimination induced by normal ventilation with 100% O2. Isocapnic hyperpnea could improve the efficacy of the standard treatment of CO poisoning, 100% O2 at atmospheric or increased pressures.

We hypothesized that CO2, like hypoxia and withdrawal of pulmonary slowly adapting receptor input, would cause tracheal constriction during neural apnea (absence of phrenic activity). In seven anesthetized paralyzed dogs ventilated to neural apnea, we increased arterial PCO2 (PaCO2) in steps by adding CO2 to the inspirate while keeping ventilation constant. Increases in PaCO2 caused tracheal constriction during neural apnea in all dogs; 69 +/- 26 (SD)% of the change in tracheal diameter occurred during neural apnea. Average sensitivity of tracheal diameter to CO2 was 0.44 mm/Torr PaCO2. Our data suggest that central chemoreceptor inputs to brain stem neurons controlling smooth muscle of the extrathoracic airway bypass central mechanisms generating inspiration.

The Doppler ultrasound (DUS) technique is a widely accepted non-invasive technique to estimate systolic blood pressure (SBP) accurately in paediatric patients. The DUS has a number of limitations. A new pulse monitor, Mr Pulse (MP), operating on the principle of a finger plethysmograph, was developed to offer an alternative technique to estimate SBP. From 104 paired SBP measurements taken in 16 paediatric patients undergoing general anaesthesia, SBP determined by the MP technique correlated closely with that by the standard DUS technique (r2 = 0.98). Analysis of degree of agreement performed indicated that there was good agreement between SBP obtained by the MP and the DUS techniques. The mean +/- standard deviation of differences in paired SBP values between the two measurement techniques was 0.55 +/- 3.59 mmHg. Mr Pulse is as accurate as the DUS technique in estimating SBP and has the advantage of less critical sensor positioning as it is not subject to electrical interference. It has no electrical hazard.

A modified thermodilution catheter (KATS catheter) capable of monitoring continuous cardiac output by thermodeprivation and preserving its conventional function was devised. The KATS catheter has a thermistor incorporated closer to the tip of the catheter in addition to the usual thermistor used for conventional thermodilution. This additional thermistor is heated by a constant electric current but is capable of measuring its own temperature. The degree of heat deprivation is detected as the cooling of the thermistor, which is proportionally larger with larger blood velocity. Since blood flow is not the only source of heat deprivation, the actual formula was empirically derived by performing in vitro studies. Cardiac output can be determined by assuming the cross sectional area of the pulmonary artery is stationary. Calibration can be derived from a cardiac output measurement by the usual thermodilution method with the same catheter. The KATS catheter readings correlated significantly with conventional thermodilution values and electromagnetic flowmeter readings in anesthetized dogs. Continuous cardiac output measurement by the KATS catheter appears to be a promising technique.

Current methods of forcing end-tidal PCO2 (PETCO2) and PO2 (PETO2) rely on breath-by-breath adjustment of inspired gas concentrations using feedback loop algorithms. Such servo-control mechanisms are complex because they have to anticipate and compensate for the respiratory response to a given inspiratory gas concentration on a breath-by-breath basis. In this paper, we introduce a low gas flow method to prospectively target and control PETCO2 and PETO2 independent of each other and of minute ventilation in spontaneously breathing humans. We used the method to change PETCO2 from control (40 mmHg for PETCO2 and 100 mmHg for PETO2) to two target PETCO2 values (45 and 50 mmHg) at iso-oxia (100 mmHg), PETO2 to two target values (200 and 300 mmHg) at normocapnia (40 mmHg), and PETCO2 with PETO2 simultaneously to the same targets (45 with 200 mmHg and 50 with 300 mmHg). After each targeted value, PETCO2 and PETO2 were returned to control values. Each state was maintained for 30 s. The average difference between target and measured values for PETCO2 was +/-1 mmHg, and for PETO2 was +/-4 mmHg. PETCO2 varied by +/-1 mmHg and PETO2 by +/-5.6 mmHg (s.d.) over the 30 s stages. This degree of control was obtained despite considerable variability in minute ventilation between subjects (+/-7.6 l min(-1)). We conclude that targeted end-tidal gas concentrations can be attained in spontaneously breathing subjects using this prospective, feed-forward, low gas flow system.

We determine whether maintaining normocapnia during hyperoxic treatment of carbon monoxide-exposed research subjects improves cerebral oxygen delivery.This experiment used a randomized, single-blinded, crossover design. We exposed 14 human research subjects to carbon monoxide until their carboxyhemoglobin levels reached 10% to 12%. We then treated each research subject with 60 minutes of hyperoxia with or without normocapnia. Research subjects returned after at least 24 hours, were reexposed to carbon monoxide, and were given the alternate treatment. Relative changes in cerebral oxygen delivery were calculated as the product of blood oxygen content and middle cerebral artery velocity (an index of cerebral blood flow) as measured by transcranial Doppler ultrasonography.Maintaining normocapnia during hyperoxic treatment resulted in significantly higher cerebral oxygen delivery compared with standard oxygen treatment (P.05; 95% confidence interval at 60 minutes 2.8% to 16.7%) as a result of the prevention of hypocapnia-induced cerebral vasoconstriction and more rapid elimination of carbon monoxide due to increased minute ventilation.If severely poisoned patients respond like our research subjects, maintaining normocapnia during initial hyperoxic treatment of carbon monoxide poisoning may lead to increased oxygen delivery to the brain. Determining the effect of such a change in conventional treatment on outcome requires clinical studies.

Cerebrovascular reactivity can be quantified by correlating blood oxygen level dependent (BOLD) signal intensity with changes in end-tidal partial pressure of carbon dioxide (PCO2). Four 3-min cycles of high and low PCO2 were induced in three subjects, each cycle containing a steady PCO2 level lasting at least 60 sec. The BOLD signal closely followed the end-tidal PCO2. The mean MRI signal intensity difference between high and low PCO2 (i.e., cerebrovascular reactivity) was 4.0 ± 3.4% for gray matter and 0.0 ± 2.0% for white matter. This is the first demonstration of the application of a controlled reproducible physiologic stimulus, i.e., alternating steady state levels of PCO2, to the quantification of cerebrovascular reactivity. Magn Reson Med 45:1011–1013, 2001. © 2001 Wiley-Liss, Inc.

Background We tested the hypothesis that the pressure-time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy. Methods In an isolated, nonperfused, lavaged model of acute lung injury, tidal volume and positive end-expiratory pressure were set to obtain: (1) a straight P-t curve (constant compliance, minimal stress); (2) a downward concavity in the P-t curve (increasing compliance, low volume stress); and (3) an upward concavity in the P-t curve (decreasing compliance, high volume stress). The P-t curve was fitted to: P = a. tb +c, where b describes the shape of the curve, b = 1 describes a straight P-t curve, b < 1 describes a downward concavity, and b > 1 describes an upward concavity. After 3 h, lungs were analyzed for histologic evidence of pulmonary damage and lavage concentration of inflammatory mediators. Ventilator-induced lung injury occurred when injury score and cytokine concentrations in the ventilated lungs were higher than those in 10 isolated lavaged rats kept statically inflated for 3 h with an airway pressure of 4 cm H2O. Results The threshold value for coefficient b that discriminated best between lungs with and without histologic and inflammatory evidence of ventilator-induced lung injury (receiver-operating characteristic curve) ranged between 0.90-1.10. For such threshold values, the sensitivity of coefficient b to identify noninjurious ventilatory strategy was 1.00. A significant relation (P < 0.001) between values of coefficient b and injury score, interleukin-6, and macrophage inflammatory protein-2 was found. Conclusions The predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.

The currently recommended prehospital treatment for carbon monoxide (CO) poisoning is administration of 100% O(2). We have shown in dogs that normocapnic hyperpnea with O(2) further accelerates CO elimination. The purpose of this study was to examine the relation between minute ventilation (V E) and the rate of elimination of CO in humans. Seven healthy male volunteers were exposed to CO (400 to 1,000 ppm) in air until their carboxyhemoglobin (COHb) levels reached 10 to 12%. They then breathed either 100% O(2) at resting V E (4.3 to 9.0 L min) for 60 min or O(2) containing 4.5 to 4.8% CO(2) (to maintain normocapnia) at two to six times resting V E for 90 min. The half-time of the decrease in COHb fell from 78 +/- 24 min (mean +/- SD) during resting V E with 100% O(2) to 31 +/- 6 min (p0. 001) during normocapnic hyperpnea with O(2). The relation between V E and the half-time of COHb reduction approximated a rectangular hyperbola. Because both the method and circuit are simple, this approach may enhance the first-aid treatment of CO poisoning.

Increases in exhaled nitric oxide have been demonstrated to originate from the lungs of rats after septic lung injury. The aim of this study was to investigate whether treatment with the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME) would prevent lipopolysaccharide (LPS)-induced increases in exhaled nitric oxide and whether this would have an effect on septic lung inflammation.Prospective, randomized, placebo-controlled animal laboratory investigation.University laboratory.Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 27).Rats were mechanically ventilated with air filtered to remove nitric oxide (expiratory rate 40 breaths/min, tidal volume 3 mL, positive end-expiratory pressure 0, FIO2 0.21). They were then randomized to receive intravenous injections of either L-NAME (25 mg/kg/hr x 4 hrs) (n = 11) or saline (n = 10). Both groups were again randomized to receive either LPS (Salmonella typhosa: 20 mg/kg i.v. x 1 dose) or an equal volume of saline 5 mins later. Thereafter, exhaled gas was collected in polyethylene bags for measurements of nitric oxide concentration. After 4 hrs, the rats were killed and the lungs were preserved and examined histologically. To examine the effect of L-NAME and LPS on mean arterial blood pressure, six additional rats underwent the same ventilation protocol with cannulation of the right internal carotid artery so that systemic arterial pressures could be measured.Exhaled gas was collected and measurements of NO concentrations were made using chemiluminescence every 20 mins for 240 mins during ventilation. A total lung injury score was calculated by determining the extent of cellular infiltrate, exudate and hemorrhage. Mean arterial pressure was recorded every 5 mins for 20 mins and then at 20-min periods for 120 mins. Exhaled nitric oxide concentrations increased in all the LPS-treated rats that did not receive L-NAME by 120 mins; a plateau was reached by 190 mins that was approximately 4 times greater than control rats not treated with LPS (p.001). In contrast, rats treated with L-NAME and LPS did not show an increase in exhaled NO. Administration of L-NAME induced a 10-min nonsustained increase in mean arterial pressure in two rats treated with L-NAME followed by LPS. This increase in mean arterial pressure was not seen in two placebo and two LPS-treated rats that did not receive L-NAME. Lung inflammation was significantly worse in the two groups of rats which received LPS compared with the two that did not. L-NAME did not cause lung inflammation in rats that did not receive LPS; however, LPS-treated rats that received L-NAME had more inflammatory interstitial infiltrate (p.05) and a trend toward worse lung injury than did LPS-treated rats that did not receive L-NAME.We conclude that L-NAME can inhibit the increase in exhaled NO from the lungs of septic rats, but that this inhibition does not reduce lung inflammation, and may worsen it.

Nitric Oxide (NO) has been implicated in the pathologic vasodilation of sepsis. Because NO can be measured in the exhaled gas of animals and humans, we hypothesized that increases in exhaled NO would occur in a septic model. Using a blinded design, 10 male Sprague-Dawley rats (300 to 400 g) were anesthetized, paralyzed, tracheotomized, and randomized (5/group) to receive an intravenous injection of either lipopolysaccharide (LPS) (Salmonella typhosa, 20 mg/kg) or placebo (equal volume of saline). Thereafter, exhaled gas was collected and measurements of NO concentration were made using chemiluminescence every 20 min for 300 min during ventilation (RR 40 breaths/min, VT 3 ml; PEEP 0, FIO2 0.21). Another group of 10 animals (5 LPS; 5 control) were treated in the same fashion and then killed at 240 min and an arterial blood sample obtained for blood gas and TNF alpha determinations. Pressure volume (PV) curves were constructed and lungs removed, preserved, and submitted for histologic evaluation. LPS-treated rats had lower mean arterial pressures than the control group, p0.0001. No significant differences in static lung compliance and PV curves were found in the two groups. TNF alpha levels were greater in the LPS group (1.40 +/- 0.24 ng/ml) versus control group (0.09 +/- 0.04 ng/ml), p0.001. By contrast to the control group, exhaled NO concentration rose in all LPS-treated rats at approximately 100 min and at about 160 min reached a plateau that was 6 times greater than control levels (p0.0001). There was greater interstitial, airspace, and total lung injury in the LPS group (p = 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

We describe and validate a new minimally invasive method for continuous measurement of tracheal diameter in anesthetized dogs. The method is based on measuring displacement of water into and out of a modified endotracheal tube cuff placed in the trachea. The system was calibrated to allow tracheal diameter to be calculated from known cuff volume. The resolution of the method in measuring changes in tracheal diameter is 0.1 mm over a range of approximately 10–25 mm. The apparatus was tested in five dogs by observing the response of the trachea to four stimuli previously shown to alter tracheal tone: stimulation of nasal mucosa, hyperinflation of the lungs, induction of hypocapnea, and infusion of atropine. The observed changes in tracheal diameter were generally consistent with those of previous studies. The direction and extent of changes in tracheal diameter in response to the test conditions were confirmed by fluoroscopy. We conclude that continuous measurement of volume changes in the cuff reflects corresponding changes in tracheal diameter.

To determine the minimum alveolar concentration (MAC) and hemodynamic responses to halothane, isoflurane, and sevoflurane in newborn swine, 36 fasting swine 4-10 days of age were anesthetized with one of the three volatile anesthetics in 100% oxygen. MAC was determined for each swine. Carotid artery and internal jugular catheters were inserted and each swine was allowed to recover for 48 h. After recovery, heart rate (HR), systemic systolic arterial pressure (SAP), and cardiac index (CI) were measured awake and then at 0.5, 1.0, and 1.5 MAC of the designated anesthetic in random sequence. The (mean +/- SD) MAC for halothane was 0.90 +/- 0.12%; the MAC for isoflurane was 1.48 +/- 0.21%; and the MAC for sevoflurane was 2.12 +/- 0.39%. Awake (mean +/- SD) measurements of HR, SAP, and CI did not differ significantly among the three groups. Compared to the awake HR, the mean HR decreased 35% at 1.5 MAC halothane (P less than 0.001), 19% at 1.5 MAC isoflurane (P less than 0.005), and 31% at 1.5 MAC sevoflurane (P less than 0.005). Compared to awake SAP, mean SAP measurements decreased 46% at 1.5 MAC halothane (P less than 0.001), 43% at 1.5 MAC isoflurane (P less than 0.001), and 36% at 1.5 MAC sevoflurane (P less than 0.005). Mean SAP at 1.0 and 1.5 MAC halothane and isoflurane were significantly less than those measured at equipotent concentrations of sevoflurane (P less than 0.005). Compared to awake CI, mean CI measurements decreased 53% at 1.5 MAC halothane (P less than 0.001) and 43% at 1.5 MAC isoflurane (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

To determine whether end-tidal PCO2 (PETCO2) measurements obtained with two infrared capnometers accurately approximates the arterial PCO2 (PaCO2) in critically ill neonates, simultaneous measurements of PETCO2 were obtained from the distal and proximal ends of the tracheal tube with a sidestream capnometer (Puritan Bennett/Datex--BP/D) and from the proximal end with a mainstream capnometer (Hewlett-Packard-HP) in 20 intubated neonates. Distal sidestream PETCO2 and mainstream PETCO2 correlated with the PaCO2 (r2 = 0.66 and 0.61, respectively) within the range of 26-57 mmHg PaCO2. However, proximal PETCO2 with the sidestream capnometer correlated very poorly (r2 = 0.09) with PaCO2. The slope of the least square regression line for the distal sidestream capnometer, 0.67, was significantly less than that for the mainstream capnometer, 0.78 but both were significantly greater than that for the proximal sidestream capnometer, 0.39 (P less than 0.05). The slope of the regression for the proximal sidestream capnometer did not differ significantly from horizontal. Insertion of the mainstream sensor for the HP capnometer significantly increased the transcutaneous CO2 when compared with preinsertion values. We conclude that both distal sidestream and mainstream capnometry provide accurate estimates of the PaCO2 in critically ill neonates.

Many studies of respiratory control require a constant CO2 to eliminate it as a confounding variable. Methods for controlling CO2 generally rely on feedback circuits which are subject to phase lags and instabilities. In 1998, we introduced a simple circuit ([1]; Fig. ​Fig.1A)1A) which stabilizes CO2 levels regardless of increases in ventilation. It passively adds CO2 to the circuit from an external source at a rate proportional to any increase in ventilation above control. Because the CO2 in this reserve gas has a PCO2 equal to that in mixed venous blood, it cannot contribute to pulmonary CO2 exchange. Figure 1 Alternatively, CO2 can be supplied from previously exhaled gas. Banzett and colleagues [2] suggested one version. Our version (Fig. ​(Fig.1B)1B) operates on the same principle but is more compact, relying on a simple bypass valve between the inspiratory and expiratory lines and which opens only when the fresh gas reservoir is exhausted. When ventilation exceeds the fresh gas flow, the 'extra' gas inhaled will be expired gas from the preceding expiration. Pro-portional rebreathing of expired gas with a PCO2 approximately equal to that of mixed venous blood prevents hypocapnia. Moreover, if the fresh gas flow consists of a hyperoxic gas mixture, such as 100% O2, partial rebreathing ensures that FIO2 remains close to that of the administered gas. Is an external gas source mandatory for maintaining isocapnia regardless of ventilatory level? The circuit in the black box contains no compressed gas or electronics. We challenge you to breathe through it and a) change your expired CO2 level using any breathing pattern you want, and b) explain how our circuit works. Possible applications for this "mystery circuit" include preventing hyperventilation-induced hypocapnia in acute mountain sickness and resuscitation of asphyxiated neonates [3].

Percutaneous needle tracheostomy and transtracheal ventilation continues to be advocated for the management of upper airway obstruction. Recent studies recommend the use of artificial ventilation. However, as apparatus for this is not always available and because there remains some doubt regarding conditions for successful use of needle tracheostomy during spontaneous respiration, we undertook such a study in dogs. Pressure-flow characteristics of short hollow needles 18–10 SWG were first determined. The smallest of these (14 SWG Bardic Intracath) that would deliver flow sufficient (by calculation) to meet the respiratory requirement of 10–13 kg laboratory dogs was selected for further study. Respiration was possible by spontaneous or artificial methods in the presence of complete tracheal occlusion. Little or no deterioration was noted in an hour of such breathing. Artificial ventilation by machine and by hand could considerably lower PaCO2. We conclude that the technique is possible provided appropriate needles are selected and care is given to their method of use.

We have previously demonstrated that diaphragmatic muscle fatigue can be diagnosed in infants from spectral frequency analysis of the surface diaphragmatic electromyogram. This requires a digital computer, but the analysis takes several days. Spectral frequency changes, however, can be accurately reflected by band pass filtering and expressing the ratio of high-frequency power to low-frequency power. A fall in this ratio of greater than 20% indicates muscle fatigue. Using a simple analog device to obtain this ratio permits the results to be immediately available; we have used this method to study weaning from mechanical ventilators in ten infants. With a successful weaning step there is no significant change in the ratio, whereas an unsuccessful weaning step invariably leads to a decrease in the ratio of greater than 20%, which precedes CO2 retention and clinical deterioration. These data indicate that diaphragmatic muscle fatigue plays an important role in the infant's response to lung disease. Monitoring of the high/low frequency ratio may be helpful in weaning infants from assisted ventilation.

A device using modification of a Pitot tube has been designed for measurement of tidal volume in infants and small children. Its accuracy was compared both n vitro and n vivo to that of a calibrated pneumotachograph (Fleish #1) designed for a similar flow range. In vitro measurement of air flow with the modified Pitot tube (MPT) was within 5% of the pneumotachograph readings over a range of 1-60 l/min. Similar accuracy was found with measurement of tidal volumes from 20 ml to 1 l, delivered by a calibrated volume-cycled ventilator using a variety of inspiratory flow rates. Tidal volume measurements with the MPT were compared to the pneumotachograph using helium, oxygen, carbon dioxide, and a range of nitrous oxide/oxygen mixtures. A manual control was incorporated into the MPT electronics to allow direct measurements of tidal volume with different nitrous oxide/oxygen concentrations. In vivo, the insertion of the MPT into the patient circuit caused no apparent changes in ventilatory parameters in children under 20 kg. Measurement of tidal volumes with the MPT agreed to within 8% of pneumotachograph readings. The low dead space (1.5 cc) and light weight (12 gm) of the MPT confer advantages over the pneumotachograph (15 ml dead space and a weight of 90 gm) for routine use in pediatric anesthesia.

A method for measuring regional myocardial blood flow with a polarographic hydrogen-clearance technique, and its experimental application in dogs, are described. Under pentobarbitone anaesthesia, flow to the superficial (3 mm) and deep (8 mm) layers of the left ventricle was not significantly different. Neither hypocapnia (PaCO2 = 24 mm Hg) nor halothane significantly altered differential distribution of blood flow to the superficial and deep layers of the myocardium. Hypocapnia was followed by a fall in myocardial blood flow (MBF) associated with increased myocardial vascular resistance (MVR). Administration of halothane 0.5 per cent at normal levels of PaCO2 led to a fall in MBF of approximately 20 per cent with no significant changes in MVR.

To assess the augmented delta quotient (ADQ) monitor as a monitor of cerebral function during cardiac surgery, we monitored during operation the electroencephalograms of 48 young subjects (aged 2 weeks to 19 yr). We found ADQ patterns produced by cardiopulmonary bypass, hypothermia and general anaesthetic agents correlated with those obtained from a compressed spectral array (CSA) monitor and could be differentiated from changes caused by cerebral ischaemia, except in the youngest group of patients (less than or equal to 18 months) undergoing deep hypothermia (19.4 (SD 0.8) degrees C nasopharyngeal). In all other age groups the ADQ proved to be a simple monitor of the adequacy of cerebral perfusion. Neurological deficit occurred only if the ADQ was abnormal during hypotension for a period exceeding 7 min. ADQ evaluation of cerebral function was limited by events which produced artificially normal ADQ readings such as low amplitude EEG activity and the described isoflurane effect that was demonstrated to occur in some cardiac patients. The results obtained by the ADQ were comparable to those obtained by compressed spectral array and the ADQ was easier to use and interpret.

IN CHILDREN, the compliance of the lung is related to height and vital capacity 1,2,a as is the total compliance of the thorax. 4 If the volume history of the lung is standardized before measurement of compliance early in anaesthesia, there is evidence from adult subjects that values for static compliance differ little from those reported in normal conscious subjects. 5 It has been shown that in normal anaesthetized children, the compliance of the total thorax, lung, and chest wall are related to height and predicted vital capacity and furthermore, that lung compliance measured early in anaesthesia has a value similar to that reported for conscious children. 6,7 This relationship allows compliance to be compared under anaesthesia in normal children and young children with cardiorespiratory disease who are difficult to study in the conscious state. The anaesthetic technique involves the use of halothane, which has no effect upon lung compliance s and d-tubocurarine, which has on occasion caused broncho-constriction ~ which may be associated with a decrease in the lung compliance, a~ In dogs, d-tubocurarine has been found both to reduce lung compliance and to decrease collateral ventilation, n In man, although this relaxant does not produce significant changes in the compliance of the total thorax 12,13 the effects on the lung have not been differentiated from those on the chest wall. An effect upon the lung could be opposed by the effect of muscle relaxation upon the chest wall and abdomen. Since any effect of curare upon the elastic recoil of the lung must influence the results of comparative studies in young children, the static elastic recoil of the total thorax, lung, and chest wall was measured before and after the intravenous administration of this agent to 10 normal children. METHODS The subjects studied were 10 children aged 7-15 years, with no evidence of cardio-pulmonary disease, who were undergoing orthopaedic operations. Anaesthesia was induced with thiopentone, 5 mg/kg, with atropine, 0.02 rag/ kg. A cuffed endotracheal tube was passed under succinylcholine paralysis and an oesophageal balloon inserted to the lower oesophagus. When spontaneous

Because anaesthesia and artificial ventilation may be associated with reduction of FRC leading to hypoxaemia, we measured changes in FRC and compliance during anaesthesia (0.5 per cent to 1 per cent methoxyflurane) and artificial ventilation in children with normal respiratory function undergoing operation on the limbs and in children with congenital cardiac anomalies undergoing surgical correction. After induction of anaesthesia in the normal children FRC fell in 35 per cent and remained at a fairly steady level throughout the operation. The lesser post-induction fall of 20 per cent observed in the children undergoing cardiac surgery was followed by a continued decrease in FRC during the surgical operation. At the end of operation the reduction in FRC was of similar magnitude in each group of children.

IN NEUROSURGICAL ANAESTHESIA, there is a place for a volatile agent which will cause neither a significant rise in cerebral blood flow (CBF) nor an increase in intracranial pressure. Most inhalational agents in concentrations greater than 1 MAC increase both cerebral blood flow and intracranial pressure.l-7 Of the agents whose effects have been reported, methoxyflurane in low concentration appears to cause the least rise in cerebro-spinal fluid (CSF) pressure in patients undergoing neurosurgical procedures, whether or not a space-occupying lesion exists. Fitch s showed that methoxyflurane (0.5 per cent inhaled concentration) caused an insignificant change in CSF pressure in patients with normal csF pathways and only a small rise in those with a space occupying lesion. Wollman et al2 found that with cyclopropane and diethyl ether cerebral blood flow in man was decreased during light anaesthesia and that cerebral perfusion increased as anaesthesia was deepened. The explosive risk limits the usefulness of these agents in neurosurgery. Since a non-explosive agent which produces little change in CSF pressure and CBF might have considerable clinical advantages, the effects of light methoxyflurane anaesthesia on CBF were studied in dogs.

This paper is the first part of a report on a method of measuring FRC by the helium dilution method in anaesthetized children during artificial ventilation. It describes laboratory investigations of the effects of different concentrations of oxygen, nitrogen and methoxyflurane upon the accuracy with which known volumes can be determined in a “dummy lung.” For a volume of 500 ml the coefficient of variation was

La capacite fonctionnelle residuelle est diminuee durant l’anesthesie et chez les patients ventiles avec pression positive intermittente.2,3 Une ventilation rapide et superficielle avec maintien d’une pression legerement positive en fin d’expiration peut prevenir cette reduction.4,5

SUMMARY Six intact and seven splenectomized dogs were subjected to a similar degree of hypoxaemia while under light anaesthesia and artificial ventilation. In the intact animals, heart rate, cardiac output, myocardial contractility and oxygen consumption were increased as a result of hypoxaemia; oxygen transport was not affected. In the splenectomized animals the changes in cardiac output and myocardial contractility were small, and oxygen availability was decreased.

It is generally believed that there is a scarcity of muscle spindles in the diaphragm and that there is no tonic activity at end expiration. This conclusion is based mainly on animal studies and the difficulty in differentiating tonic electromyogram activity from noise. We have, however, found a number of muscle spindles in the newborn human diagphragm, concentrated in the region of the central tendon. We also tried to detect tonic activity by decreasing it (by rapid-eye movement (REM) sleep or anesthesia) or increasing it (with abdominal loading). During REM sleep in five infants and five adults, using subcostal electrodes were observed a marked fall in tonic activity (P less than 0.001) compared to non-REM or quiet sleep. We also observed a reduction in diaphragmatic tonic activity with halothane anesthesia (P less than 0.001). With esophageal electrodes in adult subjects, there was a rise in tonic diaphragmatic activity proportional to the amount of abdomina load (P less than 0.001). We conclude that there are muscle spindles in the human diaphragm and that there is tonic activity at end expiration.

The volume recruitment manoeuvre is a non-invasive technique used to measure respiratory mechanics in infants. Because airway pressure increases during this manoeuvre, lung volume, compliance and cardiac output may change. In order to assess possible changes in cardiopulmonary function caused by the volume recruitment manoeuvre, we applied this technique to seven intubated infant swine breathing spontaneously during anaesthesia with halothane and N2O. Tidal volume (VT), respiratory frequency, arterial blood gases, cardiac output (CO) and total respiratory compliance were measured before and after the manoeuvre. In three swine functional residual capacity (FRC) was measured by helium dilution before the manoeuvre, and in four swine diaphragmatic EMG was recorded continuously. Finally, all swine were paralysed during volume recruitment to assess the contribution of the respiratory muscles to post-manoeuvre respiratory mechanics. VT and f increased immediately after the manoeuvre but there were no significant changes in PaCO2, or alveolar to arterial oxygen gradient. There was a small but statistically significant decrease in CO. Compliance increased by 17.8 +/- 3.6 per cent and FRC increased by a mean of 41.1 ml (or 51.9 per cent increase above the baseline FRC). The increase in FRC could not be explained by active mechanisms since the diaphragmatic EMG showed no post-inspiratory activity and neuromuscular paralysis did not decrease FRC. We conclude that the volume recruitment manoeuvre increases FRC and compliance by recruiting collapsed alveoli, and this effect must be taken into consideration when applying this test to infants.

We have compared cardiac output, gas exchange and pulmonary mechanics during spontaneous breathing and artificial ventilaton under conditions which kept PaCO2 within the normal range and maintained constant tidal volume and inspired gas flow rate. In dogs anaesthetized with pentobarbitone and ventilated with air, artificial ventilation increased VD/VT but did not reduce Q angstrom, FRC, or CL. PaO2 increased and A-aDO2 decreased during aritificial ventilation, perhaps because of a small increase in Q angstrom and a small decrease in oxygen consumption. It appears that many of the reported deleterious effects of artificial ventilation may be due to the use of other anaesthetic agents and patterns of ventilation, and to changes in PaCO2.

The effects of Althesin anaesthesia upon cerebral blood flow and cerebrospinal fluid pressure were studied in seven dogs. Althesin caused no increase of cerebral blood flow or elevation of cerebrospinal fluid pressure, suggesting that further studies should be carried out on the use of Althesin anaesthesia for neurosurgery and neuroradiology.

THE EFFECT OF HYPOXAEMIA upon the cerebral blood flow (CBF) has been studied in anaesthetised animals, 1-:~ but only intravenous anaesthetic agents, usually pentobarbitone, have been investigated. No studies have been made of the effect of induced hypoxaemia upon Cur in animals under inhalational anaesthesia. The present study was undertaken to determine the effect of hypoxacmia upon CBF at two levels of anaesthesia with methoxyflurane. METHODS Beagle dogs whose weight ranged from 9-15 kg were anaesthetised with pentobarbitone (30 mg/kg) intravenously and intubated with a cuffed endotracheal tube. A femoral artery and vein were catheterised and the arterial catheter advanced into the thoracic aorta. The venous catheter was placed in the right atrium. The vertebral artery was eannulated either directly via the internal mammary artery or from a femoral artery using the Seldinger technique. Arterial pressure was measured continuously by means of a Bell and Howell transducer and Beckman Dynograph recorder; EEC was recorded throughout. A three-way tap attached to the aortic catheter permitted the withdrawal of blood for blood gas analysis and estimation of cardiac output by means of a Waters euvette and densitometer, eardio-green dye being used as indicator. The dogs were placed on a heating blanket to maintain temperature close to 35~ They were then paralysed with a single dose of sueeinylcholine chloride (1.5mg/kg) and ventilated for 30 minutes with air and sufficient methoxyflurane from a Pentee vaporizer to produce end-tidal values of 0.3 per cent in four dogs and 0.6 per cent in another four dogs. The Harvard Respiratory Pump was set to deliver a tidal volume of 200 ml and end-tidal carbon dioxide concentration was maintained at a constant level by varying the respiratory rate. Cerebral blood flow was measured and calculated by the technique previously described? Cardiac output was measured before and after each injection of l:*:~Xe and arterial blood samples analysed at regular intervals for pH, Pco._,, and Po~. The blood gas results were corrected for temperature change. Arterial hypoxaemia was then induced by ventilating the dogs at the same tidal volume with a mixture of 10 per cent oxygen in nitrogen. The ventilator rate was adjusted to produce arterial carbon dioxide tensions similar to those obtained during ventilation with ~From the Research Institute, The Hospita] for Sick Children, and Departments of Anaesthesia, Paediatric~, and Medical Biophysics University of Toronto.

Oxygenation and mean lung volume were investigated during high frequency oscillation (HFO) and conventional mechanical ventilation (CMV) in two models of lung disease and related to the lung mechanics of the lesions. Oleic acid (n = 10) or lung lavage (n = 12) pulmonary injury was induced in a series of rabbits. Each animal was alternately ventilated with HFO (15 Hz sinusoidal wave form) and CMV (flow generator I:E, 1:2; f, 30 breaths/min; VT, 10 to 15 ml/kg) at matched mean airway pressure. Pao2 was measured 5 minutes after onset of ventilation. In the lung lavage model Pao2 was significantly greater during HFO than CMV (Pao2 228 +/- 116 torr vs 71 +/- 42 torr) provided that mean airway pressure was greater than the distinct opening pressure characteristic of this lesion. In the oleic acid model oxygenation was again superior during HFO (Pao2 269 +/- 116 torr vs 110 +/- 83 torr), but only if HFO was preceded by a sustained inflation. Plethysmography in a subset of six rabbits from each group revealed that the improvements in oxygenation were associated with significantly higher mean lung volumes during HFO than CMV (58 +/- 30 ml vs 29 +/- 14 ml lung lavage model, 45 +/- 15 ml vs 30.9 +/- 13 ml on the oleic acid model). The importance of a sustained inflation in rapidly optimizing gas exchange during HFO but not CMV was demonstrated. A sustained inflation resulted in immediate and sustained increases in Pao2 (from 134 +/- 102 torr to 274 +/0 124 torr in the oleic acid model; from 115 +/- 105 torr to 291 +/- 143 torr in the lung lavage model) and mean lung volume (41.8 +/- 11 to 53.8 +/- 9.7 ml in the oleic acid model, 30.9 +/- 7.7 ml to 42.8 +/- 5 ml in the lung lavage model). It is suggested that in these two particular models of lung disease, HFO, when combined with a sustained inflation (to provide opening forces), can more fully exploit the pressure volume hysteresis of unstable lung units than CMV, thereby resulting in the larger mean lung volumes and better oxygenation observed during HFO.

Beagle dogs were anaesthetised with halothane, trichlorethylene or methoxyflurane, at various end-tidal concentrations and were ventilated to maintain arterial carbon dioxide tension constant. Under light anaesthesia, severe arterial hypoxaemia caused significant increases in cardiac output, stroke volume and heart rate and a decrease in total systemic vascular resistance. Oxygen transport values during hypoxaemia remained close to control levels measured when the dogs were breathing air, unless the arterial oxygen tension fell below 25 mm Hg. Then the oxygen transport values fell despite significant increases in cardiac output. The clinical signs of hypoxaemia were clear in the lightly anaesthetised dogs. Under deep anaesthesia, the rise in cardiac output during hypoxaemia was not significant and the total systemic vascular resistance did not fall. Oxygen transport values decreased from the control levels. Some clinical signs of hypoxaemia were less striking than in the lightly anaesthetised hypoxaemic dogs. Morbidity and mortality rates were high in this group. We conclude that the cardiovascular response to hypoxaemia was well maintained only in those dogs under light anaesthesia with the agents studied.