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Background and Objectives: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH)., Methods: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used., Results: We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly ( p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1 / GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1 / GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8)., Discussion: We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.

Atrial fibrillation is the most common arrhythmia to occur after cardiac surgery, with an incidence of 10% to 50%. It is associated with postoperative complications including increased risk of stroke, prolonged hospital stays and increased costs. Despite new insights into the mechanisms of atrial fibrillation, no specific etiologic factor has been identified as the sole perpetrator of the arrhythmia. Current evidence suggests that the pathophysiology of atrial fibrillation in general, as well as after cardiac surgery, is multifactorial. Studies have also shown that new-onset postoperative atrial fibrillation following cardiac surgery is associated with a higher risk of short-term and long-term mortality. Furthermore, it has been demonstrated that prophylactic medical therapy decreases the incidence of postoperative atrial fibrillation after cardiac surgery. Of note, the incidence of postoperative atrial fibrillation has not changed during the last decades despite the numerous preventive strategies and operative techniques proposed, although the perioperative and postoperative care of cardiac patients as such has improved., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The lysyl oxidases are extracellular copper enzymes that initiate the crosslinking of collagens and elastin, 5 human isoenzymes having been characterized so far. The crosslinks formed provide the tensile strength and elastic properties for various extracellular matrices, including vascular walls. We studied the role of the first described isoenzyme Lox by inactivating its gene in mice., Methods and Results: Murine Lox gene was disrupted by routine methods. Lox(-/-) mice died at the end of gestation or as neonates, necropsy of the live-born pups revealing large aortic aneurysms. In light microscopy, hazy and unruffled elastic lamellae in the Lox(-/-) aortas were observed, and electron microscopy of the aortic walls of the Lox(-/-) fetuses showed highly fragmented elastic fibers and discontinuity in the smooth muscle cell layers in Lox(-/-) fetuses. The wall of the aorta in the Lox(-/-) fetuses was significantly thicker, and the diameter of the aortic lumen was significantly smaller than that in the Lox(+/+) aortas. In Lox(-/-) fetuses, Doppler ultrasonography revealed increased impedance in the umbilical artery, descending aorta, and intracranial artery blood velocity waveforms, decreased mean velocities across cardiac inflow and outflow regions, and increased pulsatility in ductus venosus blood velocity waveforms., Conclusions: Lox has an essential role in the development and function of the cardiovascular system. Inactivation of the Lox gene causes structural alterations in the arterial walls, leading to abnormalities in the cardiovascular functions. Alterations in LOX activity may also play a critical role in certain human cardiovascular diseases.

Background: Rapid recovery and weaning from ventilatory support and cardiovascular stability are suggested advantages of isoflurane inhalation, in concentrations ranging from 0.1 to 0.6 vol%, for long-term sedation in mechanical ventilated patients. This study was designed to determine whether isoflurane in low concentrations impairs pulmonary gas exchange by increasing ventilation and perfusion (V(A)/Q) mismatch during lung injury., Methods: Fourteen anesthetized dogs received in random order 0, 0.25, or 0.5 vol% end-tidal isoflurane before and after induction of lung injury with oleic acid. Gas exchange was assessed by blood gas analysis and by estimating the V(A)/Q distributions using the multiple inert gas elimination technique., Results: Administration of oleic acid produced a lung injury with severe V(A)/Q mismatch and 38 +/- 4% intrapulmonary shunting of blood. During lung injury, isoflurane accounted for a dose-related increase in blood flow to shunt units from 38 +/- 4 to 42 +/- 3 (0.25 vol%) and 48 +/- 4% (0.5 vol%) (P < 0.05), dispersion pulmonary blood flow distribution from 0.94 +/- 0.07 to 1.01 +/- 0.09 (0.25 vol%) and 1.11 +/- 0.11% (0.5 vol%) (P < 0.05), and a decrease in perfusion of normal V(A)/Q units from 58 +/- 5 to 55 +/- 4 (0.25 vol%) and 50 +/- 4% (0.5 vol%) (P < 0.05) (mean +/- SE). Isoflurane decreased arterial oxygen partial pressure from 72 +/- 4 to 62 +/- 4 mmHg (0.25 vol%) and 56 +/- 4 mmHg (0.5 vol%) (P < 0.05) and oxygen delivery from 573 +/- 21 to 529 +/- 19 ml. kg. min (0.25 vol%) and 505 +/- 22 ml. kg. min (0.5 vol%) (P < 0.05). Gas exchange, perfusion of shunt and normal V(A)/Q units, and pulmonary blood flow distribution was similar in absence of lung injury with and without isoflurane. Isoflurane 0.5 vol% lowered cardiac output during all conditions (P < 0.05). CONCLUSIONS Inhalation of low concentrations of isoflurane contributed to increased V(A)/Q mismatch and decreased systemic blood flow and oxygen delivery in mechanically ventilated animals with injured lungs.

Background: Placental insufficiency may lead to fetal cardiovascular compromise. We sought to determine whether ultrasonographic parameters of fetal cardiovascular function correlate with umbilical arterial levels of biochemical markers of myocardial dysfunction and damage in placental insufficiency., Methods and Results: In 48 fetuses with placental insufficiency, umbilical artery blood was obtained at delivery for assessment of N-terminal peptide of proatrial natriuretic peptide (NT-proANP) and cardiac troponin-T (cTnT). Group 1 fetuses (n=12) had normal NT-proANP and cTnT serum concentrations. Group 2 fetuses (n=25) showed increased NT-proANP (>1145 pmol/L) and normal cTnT values. Group 3 fetuses (n=11) had increased NT-proANP and cTnT (>0.10 ng/mL) levels. The ultrasonographic parameters of fetal cardiovascular function were compared between the groups. Pulsatility indices for veins of the ductus venosus, left hepatic vein, and inferior vena cava correlated significantly with NT-proANP levels. In group 3, ductus venosus, left hepatic vein, and inferior vena cava pulsatility indices for veins were higher (P<0.01) than in groups 1 and 2. The proportion of left ventricular cardiac output of combined cardiac output was greater (P<0.05) and that of right ventricle was smaller (P<0.05) in group 3 than in group 2. In group 3, tricuspid regurgitation was noted most often (P<0.05), and right ventricular fractional shortening was less (P<0.01) than in group 2., Conclusions: Pulsatility in human fetal systemic veins correlated significantly with the cardiac secretion of ANP. Fetuses with myocardial damage demonstrate increased systemic venous pressure, a change in the distribution of cardiac output toward the left ventricle, and a rise in right ventricular afterload.

Background: Ropivacaine is a new long-acting amide local anesthetic that has been shown in animal studies to have less dysrhythmogenic and cardiotoxic potential than bupivacaine. The intravenous administration of ropivacaine has not been associated with any detrimental effects on uterine blood flow in pregnant ewes. The purpose of this randomized, double-blind study was to examine the effects of epidural ropivacaine for cesarean section on blood flow velocity waveforms in uteroplacental and fetal arteries with color Doppler ultrasound and to assess whether the block modified fetal myocardial function., Methods: Healthy parturient women with singleton, uncomplicated pregnancies at term received 115-140 mg 0.5% ropivacaine (n = 11) or 0.5% bupivacaine (n = 10) in incremental epidural doses. The first ultrasound measurement was performed before injection of the study drug. Pulsatility indexes (PI) were derived for the blood flow velocity waveforms of the maternal placental and nonplacental uterine arteries; the placental arcuate artery; and the fetal umbilical, middle cerebral, and renal arteries. The fetal heart then was examined by echocardiography. The PI of the maternal uterine arteries and the fetal umbilical artery were measured 5 min after the injection of the local anesthetic. When sensory analgesia had reached the T6-T4 level, the ultrasound measurement was repeated with the same methods and targets as in the baseline measurement., Results: Both drugs provided adequate surgical anesthesia for cesarean section. In the bupivacaine group, the PI values for the maternal placental and nonplacental uterine arteries increased significantly 5 min after the main dose (P = 0.01, P = 0.002) and when sensory analgesia had reached the T6-T4 level (P = 0.004, P = 0.01) as compared with the baseline measurement. Simultaneously, the PI in the fetal middle cerebral artery decreased significantly (P = 0.02). The PI for the maternal uterine artery increased significantly (P = 0.01) after ropivacaine administration but only on the nonplacental side and not until sensory analgesia had reached the T6-T4 level. No effect on the Doppler indexes obtained from the umbilical artery was observed in either group. There were no significant differences relative to baseline values in any fetal myocardial measurement or in any ultrasound measurement between the groups. Neither drug had any detrimental effect on Apgar scores or umbilical cord acid-base status. None of the neonates' conditions was markedly depressed according to neurobehavioral testing., Conclusions: Within this small study, epidural 0.5% ropivacaine for cesarean section did not compromise the utero-placental circulation in healthy parturient women with uncomplicated pregnancies. It provided surgical anesthesia that was equally effective as that provided by 0.5% bupivacaine.

Background: Improved matching between ventilation and perfusion (VA/Q) has been proposed to be a major advantage of partial ventilatory support compared with controlled mechanical ventilation. This study was designed to determine whether a difference in gas exchange exists between partial ventilatory support techniques that allow unsupported spontaneous breathing to occur during any phase of the mechanical ventilatory cycle and those that provide mechanical support for each spontaneous inspiratory effort., Methods: Ten anesthetized dogs with oleic acid-induced lung injury received, in random order, pressure-support ventilation (PSV) and airway pressure-release ventilation (APRV) with and without spontaneous breathing using equivalent airway pressure limits. Gas exchange was assessed by conventional blood gas analysis and by estimating the VA/Q distributions using the multiple inert-gas elimination technique., Results: During APRV, spontaneous breathing accounted for 10 +/- 1% of the total expiratory minute ventilation. Breath-to-breath ventilatory support with PSV resulted in the highest total expiratory minute ventilation (P < 0.05). During spontaneous breathing with APRV, cardiac output increased from 3.9 +/- 0.3 to 4.6 +/- 0.41.min-1 (P < 0.05), arterial oxygen tension from 75 +/- 3 to 107 +/- 8 mmHg (P < 0.05), and oxygen delivery from 567 +/- 47 to 719 +/- 73 ml.kg.min-1 (P < 0.05). PSV did not increase cardiac output, arterial oxygen tension, and oxygen delivery. Spontaneous breathing did not increase oxygen consumption. During APRV spontaneous breathing accounted for a 13 +/- 2% decrease (P < 0.05) in blood flow to shunt units (VA/Q < 0.005) and a 14 +/- 2% increase (P < 0.05) in the perfusion of normal VA/Q units (0.1 < VA/Q < 10). Pulmonary blood flow distribution to shunt and normal VA/Q units was similar during PSV and APRV without spontaneous breathing. Dead space (VA/Q > 100) ventilation decreased by 6% during APRV with spontaneous breathing compared with PSV (P < 0.05)., Conclusions: Spontaneous breathing superimposed on mechanical ventilation contributes to improved VA/Q matching and increased systemic blood flow. Apparently, the spontaneous contribution to a mechanically assisted breath during PSV is not sufficient to counteract the VA/Q maldistribution of positive pressure lung insufflation during acute lung injury.

To improve the accuracy of early detection of inadvertent esophageal intubation, we designed, trained, and tested a neural network-based computer system to detect the mechanical differences between lung and esophagogastric ventilation. Ten 25 to 30-kg anesthetized swine were sequentially ventilated with tidal volumes of 9, 12, and 15 mL/kg, using tubes placed in the trachea and in the esophagus, while flow and pressure waveforms were collected for 9-10 breaths. Gas remaining in the stomach was aspirated after each period of gastric ventilation. A computer program identified each mechanical inspiration, extracted the first 37 flow and pressure data points from each record, and normalized them to an equal amplitude. A back-propagation single-hidden-layer neural network was trained to identify the origin of flow and pressure waveforms as tracheal or esophageal. Ten different training and testing groups were assembled. In each group, data from nine subjects were used for training and data from the remaining subjects were used for testing. A total of 291 esophageal and 300 tracheal flow and pressure waveforms were analyzed by the network. The network identified esophageal intubation correctly during the first five breaths of all esophageal recordings. In one subject, the network identified the eighth esophageal breath as tracheal and could not identify three breaths. All tracheal intubations were identified correctly. Flow and pressure "signatures" of pulmonary and gastric ventilation are easily learned by a neural network. Therefore, neural-network recognition of esophageal intubation from flow and pressure signals is possible, and the development of an on-line detector for tracheal tube misplacement seems feasible.

Objective: To estimate the changes in the relative amount of ventilatory assistance offered by inspiratory pressure support during changing ventilatory demand with external airway obstruction and with oleic acid-induced acute lung injury., Design: Prospective, controlled, crossover study., Setting: Experimental laboratory in a university anesthesiology department., Subjects: Eight dogs anesthetized with pentobarbital., Interventions: An external resistor was placed in the breathing circuit to produce increased resistance to breathing. Acute lung injury was produced with oleic acid. Ventilatory demand was increased by increasing the CO2 concentration in inspired gas to produce an increase of 20 torr (2.7 kPa) in end-tidal CO2 tension. During airway obstruction, pressure support was adjusted to reduce the inspiratory decrease in intrathoracic pressure to the level present during unobstructed breathing. During acute lung injury, pressure support was applied to reduce the maximum negative deflection of intrathoracic pressure by 50%., Measurements and Main Results: The ventilator effort was estimated by calculating the pressure-time integral of proximal airway pressure; the spontaneous ventilatory effort was estimated in a similar manner from esophageal pressure. The pressure support averaged 10 +/- 3 cm H2O during airway obstruction and 7 +/- 2 cm H2O during lung injury. The CO2 challenge effected an average increase in mean minute ventilation of 78% during airway obstruction (p < .001) and 120% during acute lung injury (p < .01). The augmentation of minute ventilation was accomplished by increasing the ventilatory rate and the transpulmonary pressure while inspiratory time remained unchanged. The pressure-time integrals measured using both airway (p < .001) and esophageal pressure (p < .01) increased significantly during each CO2 challenge, reflecting an increase in the contribution of both the ventilator and the animal to the required breathing effort. Significant decreases in the relative magnitude of the ventilator effort both during airway obstruction (p < .05) and during lung injury (p < .01) indicated that the increase in the spontaneous effort was predominant over the increase in mechanical ventilatory support., Conclusions: A ventilatory rate-dependent adaptation of pressure support to increased ventilatory demand occurs in an experimental setting both during airway obstruction and lung injury. The results of this study confirm an advantage of breath-to-breath inspiratory pressure support over techniques designed to supply a predetermined mechanical minute volume.

Background: The pain of parturition is associated with major physiologic alterations mediated by neurohumoral factors and increased activation of the sympathetic nervous system. Epidural local anesthetics abolish or alleviate many of the pain-mediated responses by reducing maternal catecholamine levels, inducing sympathectomy and consequent vasodilatation. The hormone response to surgical stress is not attenuated after epidural opioids as efficiently as after local anesthetics. Opioid receptors may modulate sympathetic outflow at a spinal level. This study was performed to compare the effects of epidural sufentanil and bupivacaine on the uterine and placental circulation., Methods: Utilizing a prospective randomized, double-blind study design, 30 healthy women at term were examined employing a color Doppler technique to assess and compare the effects of analgesia using sufentanil or bupivacaine epidurally during the first stage of labor on blood flow velocity waveforms in the uterine and umbilical arteries., Results: Effective analgesia was provided by both drugs, bupivacaine and sufentanil. Uterine and umbilical blood velocity waveform indices did not change significantly. There was, however, a significantly greater incidence of fetuses with changes in heart rate tracings in the sufentanil group, decreased variability being the most frequent. Maternal side effects attributable to sufentanil were common but mild. No patient became hypotensive in either group., Conclusions: Epidural sufentanil and bupivacaine provide effective analgesia with acceptable side effects during the first stage of labor in healthy parturients. Neither drug had any detrimental effects on blood flow indexes reflecting peripheral vascular resistance in the umbilical and uterine arteries in healthy parturients.

Objective: To determine whether continuous gas flow in the breathing circuit or an airleak around the tracheal tube cuff will introduce errors into the measurement of oxygen consumption (VO2) with indirect calorimetry., Design: Nonrandomized, controlled trial., Setting: Experimental laboratory., Subjects: Ten healthy, anesthetized mongrel dogs, weighing 8 to 12 kg., Interventions: Data were recorded at seven levels of flow, from 0 to 12 L/min in excess of minute ventilation, through a continuous breathing circuit. Data were recorded at five levels of tracheal tube cuff leak from 0% to 40% of inspiratory minute volume., Measurements and Main Results: VO2 was measured using an indirect calorimeter with constant internal gas flow and calculated from results of blood gas analysis, cooximetry, and thermodilution cardiac output determinations at all levels of continuous breathing circuit flow and cuff leak. BP, heart rate, respiratory rate, arterial and mixed venous blood gases, and body temperature were measured to assess stability of cardiopulmonary function. Continuous breathing circuit flow did not affect the accuracy of indirect calorimetry until the total flow reached a critical value (11.5 L/min) that was slightly below the internal flow constant of the metabolic monitor (12.4 L/min). At higher circuit flows, measured VO2 decreased in a linear fashion, while calculated VO2 remained unchanged. Above the critical flow, the error of indirect calorimetry correlated significantly only with the total circuit flow (r2 = .64), not with the exhaled concentration of CO2 (r2 = .005) or the inspiratory-expiratory oxygen difference (r2 = .004). The continuous flow rate at the critical circuit flow was 66 +/- 15% of the subjects' peak inspiratory flow. Increasing tracheal tube cuff leak produced a progressive decrease in measured VO2 but not in calculated VO2. The difference between measured and calculated VO2 was linearly related to the magnitude of the leak (r2 = .56), and was statistically significantly larger at all levels of cuff leak, when compared with measurements during complete cuff seal., Conclusions: An indirect calorimeter in which measurement of VO2 is based on internal constant flow rather than spirometry can be used to accurately measure VO2 from a continuous-flow breathing circuit, if the total circuit flow is less than the internal flow. This limitation may restrict the use of continuous flow to a level below the subject's peak inspiratory flow. The accuracy of indirect calorimetry cannot be guaranteed for any amount of tracheal tube cuff leak.

Objective: To evaluate the feasibility of airway pressure release ventilation (APRV) in providing ventilatory support to patients with acute lung injury of diverse etiology and mild-to-moderate severity., Design: Prospective, multicenter, nonrandomized crossover trial., Setting: ICUs in six major referral hospitals., Patients: Fifty adult patients with respiratory failure requiring mechanical ventilation and positive end-expiratory airway pressure., Interventions: After optimization of continuous positive airway pressure (CPAP), conventional ventilation and APRV were administered sequentially for 30 mins. During APRV, the CPAP level and airway pressure release level were adjusted to prevent hypoxemia, while the degree of ventilatory support was adjusted by altering the frequency of pressure release., Measurements and Main Results: Circulatory and ventilatory pressures, arterial blood gases and pH, heart rate, and respiratory rate were measured. Alveolar ventilation was augmented adequately in 47 of 50 patients by APRV. Adjustment of APRV required an increase in mean CPAP from 13 +/- 3 (SD) to 21 +/- 9 cm H2O and a release pressure of 6 +/- 5 cm H2O. This airway pressure pattern produced a mean airway pressure comparable to that pressure achieved during conventional ventilation. Failure of APRV in three patients could be attributed to an inadequate level of CPAP or an inadequate APRV rate. While maintaining oxygenation of arterial blood and circulatory function, APRV allowed a substantial (55 +/- 17%; p less than .0001) reduction in peak airway pressure compared with conventional positive pressure ventilation adjusted to deliver a comparable or lower level of ventilatory support., Conclusions: APRV is a feasible alternative to conventional mechanical ventilation for augmentation of alveolar ventilation in patients with acute lung injury of mild-to-moderate severity.

Objective: To compare cardiopulmonary function during spontaneous breathing with three continuous-flow breathing circuits. The major difference between these circuits was the degree of flow resistance offered by the exhalation valve., Design: Randomized crossover trial., Patients: Twelve infants less than 12 months of age recovering from respiratory failure of variable etiology. Only patients weighing 3 to 10 kg were studied., Interventions: The patients were connected to each respiratory circuit in a random sequence, with 15 min allowed for equilibration before assessment of cardiopulmonary function. Airway pressure (Paw) and FIO2 were maintained unchanged., Measurements and Main Results: Ventilation, gas exchange, or circulatory function were not altered significantly by changing the breathing circuit. However, Paw and esophageal pressure fluctuations were altered and were largest during breathing with the circuit that had an exhalation valve with high-flow resistance. The Paw fluctuation recorded while the patient was breathing with the flow-resistor circuit increased with weight and exceeded 2 cm H2O in all patients weighing greater than 4.5 kg. Paw fluctuation could be decreased by greater than 2 cm H2O in ten of 12 patients by using the threshold-resistor circuit., Conclusions: The results indicate a need for evaluating the characteristics of respiratory circuits used for spontaneous breathing in infants and children, to avoid unnecessary equipment-related increase in respiratory work.

Transcutaneous oxygen and carbon dioxide tensions (PtcO2 and PtcCO2) were compared with PaO2 and PaCO2 values in 9 patients with pulmonary edema due to acute myocardial infarction (AMI) measured during four experimental interventions: (a) intermittent mandatory ventilation (IMV) 4/min + PEEP0 (cm H2O); (b) intermittent positive pressure ventilation (IPPV)12 + PEEP0; (c) IMV4 + PEEP10; and (d) IPPV12 + PEEP10. PtcO2 responded rapidly to the institution of PEEP, the rise correlating well with that in PaO2 both on IMV4 (r = 0.78) and IPPV12 (r = 0.87). On the other hand, correlations between PtcO2 vs CI and PvO2 were poor (r being 0.45 and 0.24, respectively). Transcutaneous oxygen electrode is, thus, useful in monitoring patients with post-AMI pulmonary edema, as it rapidly reflects the effects of ventilatory therapy. A nonheated PtcCO2 sensor was used in 6 patients and a heated electrode in 3 patients. With the nonheated electrode, the correlation between PaCO2 and PtcCo2 was good (r = 0.86) in 5 patients, while r in the 3 patients with the heated electrode was 0.73. One patient having a cardiac index of 1.6 L/min . M2 showed a dissociation in PCO2 values. While PaCO2 remained unchanged, PtcCO2 rose to 73 torr and within some minutes the patient had asystole. PtcCO2 tension generally shows good correlation with PaCO2 and, thus, reflects ventilation. It may also prove to be useful in the early detection of critical low cardiac output states.

We studied the theoretical basis for continuous monitoring of pulmonary gas exchange using arterial and mixed venous oximetry by examining the mathematical relationships between the calculated venous admixture (Qsp/Qt) and the ventilation-perfusion index, which is derived from oxyhemoglobin saturations. We compared this relationship with that between Qsp/Qt and its commonly used estimates: inspired oxygen concentration to arterial blood oxygen tension ratio, arterial to alveolar oxygen tension ratio, and alveolar-arterial oxygen tension difference. The relationship between Qsp/Qt and the oxygen tension-based indices is nonlinear and substantially influenced by changes in inspired oxygen concentration and arteriovenous oxygen content difference. Therefore, it is inaccurate within the clinically acceptable range of arterial blood oxygenation. In contrast, calculation of ventilation-perfusion index from arterial and mixed venous blood oxyhemoglobin saturations provides a linear estimate of Qsp/Qt that is minimally affected by alterations in inspired oxygen concentration or oxygen uptake and, therefore, will allow accurate continuous assessment of pulmonary gas exchange.

Total body oxygen utilization coefficient was estimated using continuous pulse and pulmonary artery oximetry (dual oximetry) in 17 patients with respiratory failure. Change in arterial and mixed venous oxygen saturations was induced by altering airway pressure. Continuous measurement of mixed venous oxygen saturation provided an accurate and linear estimate of oxygen utilization coefficient (r = -0.92), the true values being overestimated by 0.05 +/- 0.06 (mean +/- SD). Addition of pulse oximetry improved the correlation (r = 0.93) and decreased the difference between absolute values (0.02 +/- 0.06). Oxygen utilization coefficient can be estimated reliably in an online fashion using pulmonary artery oximetry. However, the use of dual oximetry will further improve the estimate.

Positive end-expiratory pressure of 10 cm H2O (PEEP10) was compared with zero-end-expiratory pressure (PEEP0), intermittent mandatory ventilation (IMV), 4/min, with intermittent positive pressure ventilation (IPPV), 12/min, in 9 patients with pulmonary edema due to acute myocardial infarction (AMI). Systemic and pulmonary arterial pressures, pulmonary capillary wedge pressure (PCWP) and CVP, cardiac output (CO) and blood gases were measured during these four experimental interventions, and related parameters calculated. PaCO2 was 39.3 +/- 0.9 torr during IMV4 and 36.2 +/- 1.3 torr during IPPV12, and PCWP remained between 20-30 mm Hg throughout the study. The ventilatory pattern was changed at random order with the patient serving as his own control. Both PaO2 and PaO2/F102 and VO2 increased while venous admixture (Qsp/Qt) decreased with PEEP10. Cardiac and stroke indices (CI, SI) and oxygen delivery were lower with IPPV12 than they were with IMV4. Both left and right ventricular stroke work (LVSW, RVSW) were higher on IMV4. A moderate PEEP level (up to 10 cm H2O) seems beneficial in post-AMI pulmonary edema and has no significant hemodynamic side effects. The results indicate that of the four alternatives studied, IMV4 with PEEP10 is a ventilatory pattern of choice in the respiratory management of these patients, but each individual patient may require precise titration of each modality to achieve the optimal result.