George Volgyesi

Pressure–Time Curve Predicts Minimally Injurious Ventilatory Strategy in an Isolated Rat Lung Model

BackgroundWe tested the hypothesis that the pressure–time (P-t) curve during constant flow ventilation can be used to set a noninjurious ventilatory strategy. MethodsIn 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 · t b +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. ResultsThe 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. ConclusionsThe predictive power of coefficient b to predict noninjurious ventilatory strategy in a model of acute lung injury is high.

The Minimum Alveolar Concentration (MAC) and Hemodynamic Effects of Halothane, Isoflurane, and Sevoflurane in Newborn Swine

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)

End-tidal carbon dioxide measurements in critically ill neonates: a comparison of side-stream and mainstream capnometers

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 < 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.RésuméEn enregistrant simultanément la PCO2 en fin d’expiration (PETCO2) par capnomètre aspirant (Puritan Bennett/Datex —PB/D) à partir du bout distal et du bout proximal d’un tube endotrachéal et par capnomètre passif (Hewlett-Packard — HP) au bout proximal du tube, nous avons mesuré l’efficacité de ces techniques d’estimation à l’infrarouge de la PCO2 artérielle (PaCO2) chez 20 nouveauxnés. Pour des PaCO2 de l’ordre de 26 à 57 mmHg, la pente de la ligne de régression entre la PETCO2 et la PaCO2 était de 0,78 avec le capnomètre passif (r2 = 0,61), significativement plus grande que la pente de 0,67 du capnomètre aspirant au bout distal (r2 = 0,66) mais toutes deux se détachaient (P < 0,05) de celle du capnomètre aspirant au bout proximal qui, avec une valeur de 0,39, pouvait être confondue avec l’horizontale (r2 = 0,09). Pour sa part, l’insertion dans le circuit de la fenêtre de mesure du capnomètre passif contribuait à augmenter la PCO2 transcutanée. La capnométrie passive ou par aspiration du bout distal donne donc un bon estimé de la PaCO2 des nouveauxnés gravement malades.

The consequences of diaphragmatic muscle fatigue in the newborn infant.

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 infants response to lung disease. Monitoring of the high/low frequency ratio may be helpful in weaning infants from assisted ventilation.

Inhibition of exhaled nitric oxide production during sepsis does not prevent lung inflammation

OBJECTIVES 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. DESIGN Prospective, randomized, placebo-controlled animal laboratory investigation. SETTING University laboratory. SUBJECTS Male, anesthetized, paralyzed, and mechanically ventilated Sprague-Dawley rats (n = 27). INTERVENTIONS 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. MEASUREMENTS AND MAIN RESULTS 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. CONCLUSION 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.

Continuous cardiac output determination by thermodeprivation.

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.

The effect of methoxyflurane on cerebral blood flow in the dog

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.

Systolic arterial pressure determination by a new pulse monitor technique

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 ofafingerplethysmograph, 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.RésuméLes appareils à ultrasons avec effet Doppler (UED) sont couramment utilisés pour évaluer de façon non-invasive la pression systolique chez les enfants. La technique des UED a plusieurs limites. Un nouveau moniteur de pouls appele « Mr. Pulse » a récemment été développé afin de permettre une autre façon d’évaluer la pression systolique. Cette nouvelle technique utilise la pléthysmographie digitale. Chez 16 patients pédiatriques, 104 mesures appariées de pression systolique ont permis d’établir qu’il existe une excellente corrélation entre les valeurs obtenues avec « Mr. Pulse » et celles obtennes avec un appareil à UED (r2 = 0,98). La concordance entre les mesures obtenues avec les deux méthodes est aussi trés bonne puisque la moyenne des différences (±écart-type) entre les valeurs mesurées par les deux techniques n’est que de 0,55 ± 3,59 mmHg. Mr. Pulse est done aussi précis que les appareils à UED dans l’évaluation de la pression systolique. Mr. Pulse a l’avantage d’avoir un capteur moins sensible au positionnement et aux interférence électriques, et il ne présente ancun risque de fuite de courant électrique.

A TECHNIQUE FOR MEASURING REGIONAL MYOCARDIAL BLOOD FLOW AND ITS APPLICATION IN DETERMINING THE EFFECTS OF HYPERVENTILATION AND HALOTHANE

SummaryA 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.RésuméCe travail décrit une méthode de mesure du flot sanguin régional du myocarde par une technique polarographique de l’élimination de l’hydrogène et son utilisation expérimentale chez le chien.Sous anesthésie au Pentobarbital, les débits sanguins mesurés dans les couches superficielle ( 3 mm ) et profonde ( 8 mm ) de la paroi du ventricule gauche n’ont montré que des différences insignifiantes.Ni l’hypocapnie (Paco2= 24 mm Hg) ni l’Halothane n’ont modifié de façon sensible la distribution du débit aux couches superficielle et profonde du myocarde. L’hypocapnie a entraîné une chute du débit sanguin myocardique accompagnée d’une augmentation de la résistance vasculaire.Sous des conditions d’eucapnie, l’administration d’Halothane (0.5 pour cent) réduit le flot sanguin myocardique d’environ 20 pour cent sans changement sensible de la résistance vasculaire.

Cardiopulmonary effects of the volume recruitment manoeuvre in infant swine.

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.RésuméLe « recrutement de volume » est une méthode de mesure atraumatique de la mécanique respiratoire des bébés. L’augmentation de la pression des voies aériennes qu’elle entraîne peut modifier la compliance et le volume pulmonaire ainsi que le débit cardiaque. Cest pour évaluer ces changements que nous avons applique la technique à sept cochonnets intubds respirant halothane-O2-N2O. Nous avons mesuré le volume courant (VT), la frequence respiratoire (f), les gaz artériels, le débit cardiaque (DC) et la compliance pulmonaire totale avant et aprés le recrutement. Par dilution d’hélium, nous avons évalué la capacité résiduelle fonctionnelle (CRF) avant la manoeuvre chez trois sujets et avons enregistré en continu l’EMG diaphragmatique des quatre autres. Enfin, nous avons isolé la contribution musculaire aux changements mécaniques en paralysant les cochons pendant une session de recrutement. Immédiatement aprés la manoeuvre, nous avons observé une augmentation du VT de f, sans changement de la PaCO2 ni du gradient alvéolo-artériel en oxygéne. La petite diminution du DC était statistiquement significative alors que la compliance croissait de 17,8 ± 3,6 pour cent et la CRF augmentait en moyenne de 41,l ml à 151, 9 pour cent des valeurs contrôles. Vu l’absence d’activité post-inspiratoire à l’EMG et l’influence nulle de la paralysie sur iaugmentation de la CRF, on peut conclure à la nature passive de ce phénomène. Les changements de la CRF et de la compliance s’ expliquent par du recrutement alvéolaire et cela doit être pris en consideration quand on applique ce test chez l’enfant.