Baseline Minute Ventilation Research Articles

Progressive augmentation and long term facilitation of ventilation is enhanced in participants with sleep apnea compared to control and is mitigated by reductions in oxidative stress

PurposeTo determine whether progressive augmentation (PA) and long‐term facilitation of minute ventilation (vLTF) is enhanced in participants with obstructive sleep apnea (OSA) compared to control. Moreover, to determine whether treatment with an antioxidant cocktail (AOX) mitigates PA and vLTF in OSA participants.Methods13 OSA and 13 controls completed two trials. During both trials participants were exposed to intermittent hypoxia (IH) which included 12‐4 minute episodes of hypoxia (PETO2 ‐ 50 mmHg, PETCO2 ‐ 4 mmHg above baseline) followed by 30 minutes of recovery. During the trials participants were administered, in a randomized fashion, either an AOX or a PLB before IH.ResultsDuring the PLB trial, baseline minute ventilation was similar between OSA and control (18.8 ± 2.1 vs. 14.8 ± 0.5 L/min). PA was evident in both groups; however it was enhanced in the OSA group compared to control (last hypoxic episode ‐ 36.9 ± 2.8 vs. 27.7 ± 2.2 L/min; p = 0.002). During end‐recovery vLTF was greater in the OSA group compared to control (27.7 ± 2.2 vs. 20.2 ± 1.2 L/min; p = 0.01). PA and vLTF were reduced in the OSA group following AOX compared to PLB (PA ‐ 30.6 ± 2.0 vs. 36.9 ± 2.8 L/min, p = 0.02; vLTF 22.3 ± 1.3 vs. 27.7 ± 2.2 L/min, p = 0.002).ConclusionsPA and vLTF is enhanced in participants with OSA compared to control. PA and vLTF is mitigated after treatment with an antioxidant cocktail.Funding: NIH (HL‐085537)

Validation of respiratory safety pharmacology models: Conscious and anesthetized beagle dogs

Introduction Installation, operation and performance qualifications were performed on a test system for respiratory monitoring. Methods For performance qualification, conscious dogs received saline (0.2 mL/kg, iv, n = 12), albuterol (100 μg/kg, inhalation, n = 5), methacholine (2.0 and 8.0 μg/kg, iv, n = 8) and remifentanil (4.0 μg/kg, iv, n = 7). Following anesthesia with propofol infusion, dogs received saline (iv, n = 15), albuterol (100 μg/kg, inhalation, n = 8), methacholine (8.0 μg/kg, iv, n = 8), remifentanil (4.0 μg/kg, iv, n = 7), and cholecystokinine tetrapeptide (CCK-4) (10 μg/kg, iv, n = 7) and were exposed to hypoxic gas mixture (10% oxygen) ( n = 12). Results Saline had no significant respiratory effect. Albuterol increased tidal volume (TV) (+ 28%, p < 0.05) and minute ventilation (MV) (+ 96%, p < 0.01) in conscious dogs. In anesthetized dogs, MV was significantly increased (+ 23%, p < 0.05) but the difference was not statistically significant for TV and respiratory rate (RR). Methacholine at 2.0 μg/kg increased MV (+ 45%, p < 0.01) in conscious animals while 8.0 μg/kg increased RR (+ 66%, p < 0.01), TV (+ 24%, p < 0.05) and MV (+ 88%, p < 0.05). In anesthetized dogs, methacholine increased RR (+ 51%, p < 0.05), MV (+ 34%, p < 0.05), lung elastance (+ 36.9%, p < 0.01), and resistance (+ 45.8%, p < 0.01). Remifentanil decreased MV in conscious dogs (− 68%, p < 0.01) while transient apnea was observed in all anesthetized dogs. CCK-4 increased RR (+ 328%, p < 0.01) and MV (+ 127%, p < 0.05) and decreased TV (− 58%, p < 0.01). Exposure to hypoxic gas mixture increased MV and RR ( p < 0.01). Baseline MV was lower ( p < 0.05) in anesthetized than in conscious dogs. Discussion Arterial blood gas values, particularly SaO 2, presented a limited sensitivity to detect any ventilation disturbance, but allowed confirmation of both ventilatory compensatory phenomenon (when present) and initial pharmacologic drug effect. These results also highlight the greater sensitivity of the conscious model when compared to anesthetized dogs.

Genetic Control of Breathing: Effects of Gender and Lung Mechanics

Robust genetic determinants regulate variation in breathing characteristics among inbred mouse strains. The current study investigates the role of lung structure and mechanics in affecting differences in breathing phenotypes. Baseline minute ventilation (VE) and breathing pattern (tidal volume, VT and frequency, f) were repeatedly measured in male and female C3H/HeJ (C3) and C57Bl/6J (B6) mice using plethysmography. Synchronized measurements of O2 consumption (VO2) and CO2 production (VCO2) were also measured. Quasistatic pressure-volume curves and respiratory impedance measurements characterized lung mechanical properties. The results suggest that VE, as referenced to the VO2 or VCO2 (Veq), in B6 mice is significantly (P < 0.05) greater than C3 mice. Moreover, VT and f correlated significantly (r-values = −0.74 and −0.78, P < 0.05) with lung elastance among all mice; however, these relationships were substantially greater in male (r-value = −0.83 and −0.92, P < 0.01) compared with female mice. In sum, robust genetic factors that regulate variation in breathing between C3 and B6 mice cosegregate with determinants of variable lung mechanical properties. Gender and variation in metabolic rate also modulate the genetic control of breathing in this model. NIA AG-21057 and NHLBI HL-010342

Respiratory syncytial virus infection in anesthetized weanling rather than adult rats prolongs the apneic responses to right atrial injection of capsaicin

Apnea is a common complication in infants infected by respiratory syncytial virus (RSV). A recent study has shown that intranasal inoculation of RSV in conscious weanling rats strengthens the apneic responses to right atrial injection of capsaicin (CAP), leading to 66% mortality. The objectives of the present study were to determine 1) whether RSV infection changes baseline minute ventilation (Ve) and arterial blood gases in anesthetized rats; 2) what the effects of RSV infection are on the respiratory responses to CAP; and 3) whether the RSV-strengthened apneic responses are age dependent. Our experiments were conducted in anesthetized and spontaneously breathing rats divided into four groups of weanling and adult rats that received either intranasal inoculation of RSV or virus-free medium. Two days after RSV infection (0.7 ml/kg), animal blood gases, baseline Ve, and Ve responses to right atrial injection of three doses of CAP (4, 16, and 64 microg/kg) were measured and compared among the four groups. Our results showed that RSV infection increased respiratory frequency (approximately 25%, P<0.05) in weanling but not adult rats, with little effect on arterial blood gases. RSV infection amplified the apneic responses to CAP in weanling but not adult rats, characterized by increases in the initial (40%) and the longest apneic duration (650%), the number of apneic episodes (139%), and the total duration of apneas (60%). These amplifications led to 50% mortality (P<0.05). We conclude that RSV infection increases respiratory frequency and strengthens the apneic responses to CAP only in anesthetized weanling but not adult rats.

Neonatal maternal separation induces sex-specific augmentation of the hypercapnic ventilatory response in awake rat

Neonatal maternal separation (NMS) is a form of stress that exerts persistent, sex-specific effects on the hypoxic ventilatory response. Adult male rats previously subjected to NMS show a 25% increase in the response, whereas NMS females show a response 30% lower than controls (8). To assess the extent to which NMS affects ventilatory control development, we tested the hypothesis that NMS alters the ventilatory response to hypercapnia in awake, unrestrained rats. Pups subjected to NMS were placed in a temperature- and humidity-controlled incubator 3 h/day for 10 consecutive days (P3 to P12). Control pups were undisturbed. At adulthood (8 to 10 wk old), rats were placed in a plethysmography chamber for measurement of ventilatory parameters under baseline and hypercapnic conditions (inspired CO(2) fraction = 0.05). After 20 min of hypercapnia, the minute ventilation response measured in NMS males was 47% less than controls, owing to a lower tidal volume response (22%). Conversely, females previously subjected to NMS showed minute ventilation and tidal volume responses 63 and 18% larger than controls respectively. Although a lower baseline minute ventilation contributes to this effect, the higher minute ventilation/CO(2) production response observed in NMS females suggests a greater responsiveness to CO(2)/H(+) in this group. We conclude that NMS exerts sex-specific effects on the hypercapnic ventilatory response and that the neural mechanisms affected by NMS likely differ from those involved in the hypoxic chemoreflex.

Long-term facilitation of ventilation and genioglossus muscle activity is evident in the presence of elevated levels of carbon dioxide in awake humans

We hypothesized that long-term facilitation (LTF) of minute ventilation and peak genioglossus muscle activity manifests itself in awake healthy humans when carbon dioxide is sustained at elevated levels. Eleven subjects completed two trials. During trial 1, baseline carbon dioxide levels were maintained during and after exposure to eight 4-min episodes of hypoxia. During trial 2, carbon dioxide was sustained 5 mmHg above baseline levels during exposure to episodic hypoxia. Seven subjects were exposed to sustained elevated levels of carbon dioxide in the absence of episodic hypoxia, which served as a control experiment. Minute ventilation was measured during trial 1, trial 2, and the control experiment. Peak genioglossus muscle activity was measured during trial 2. Minute ventilation during the recovery period of trial 1 was similar to baseline (9.3 +/- 0.5 vs. 9.2 +/- 0.7 l/min). Likewise, minute ventilation remained unchanged during the control experiment (beginning vs. end of control experiment, 14.4 +/- 1.7 vs. 14.7 +/- 1.4 l/min). In contrast, minute ventilation and peak genioglossus muscle activity during the recovery period of trial 2 was greater than baseline (minute ventilation: 28.4 +/- 1.7 vs. 19.6 +/- 1.0 l/min, P < 0.001; peak genioglossus activity: 1.6 +/- 0.3 vs. 1.0 fraction of baseline, P < 0.001). We conclude that exposure to episodic hypoxia is necessary to induce LTF of minute ventilation and peak genioglossus muscle activity and that LTF is only evident in awake humans in the presence of sustained elevated levels of carbon dioxide.

Interaction of arousal states and low dose halothane on the acute hypercapnic ventilatory response in humans

The purpose of this study was to examine the effect of low dose halothane on the acute ventilatory response to hypercapnia, and to assess whether arousal (due to audiovisual (AV) stimulation or pain) modulates the response to halothane. Single step increases in end-tidal Pco(2) using dynamic end-tidal forcing were performed from eucapnia (end-tidal Pco(2) held 1 mmHg (0.13 kPa) above ambient) to hypercapnia (end-tidal Pco(2) 6 mmHg (0.79 kPa) above ambient) in eight healthy volunteers, with end-tidal PO(2) held at 100 mmHg (13.2 kPa), in six protocols: 1) control conditions (darkened, quiet room, eyes closed) without halothane; 2) control conditions with 0.1 MAC halothane; 3) AV stimulation (bright room, loud television) without halothane; 4) AV stimulation with 0.1 MAC halothane; 5) pain (electrical stimulation of skin over tibia to produce visual analogue pain score 5-6/10) without halothane; 6) pain with 0.1 MAC halothane. Both AV stimulation (p = 0.014) and pain (p = 0.0003) significantly increased the baseline eucapnic minute ventilation modestly (by approximately 1.5-4 l.min(-1)). Halothane did not influence the baseline minute ventilation in any arousal state (p = 0.572), nor did it affect the hypercapnic ventilatory response in any arousal state (p = 0.208). Arousal (either AV stimulation or pain) did not affect the ventilatory response to CO(2), regardless of the presence or absence of halothane (p = 0.585). We conclude that halothane affects neither baseline minute ventilation nor the response to CO(2). Arousal can increase baseline ventilation but has no influence on the ventilatory response to CO(2).

Effect of prolongation of expiratory time on dynamic hyperinflation in mechanically ventilated patients with severe asthma.

To assess the effect of a decrease in respiratory rate on dynamic hyperinflation, as determined by changes in plateau airway pressure, in patients with status asthmaticus whose baseline minute ventilation approximated 10 L/min. Observational descriptive study. Medical intensive care unit. Twelve patients with severe asthma mechanically ventilated in the assist control mode with a tidal volume of 613 +/- 100 mL and an inspiratory flow rate of 79 +/- 4 L/min. A decrease in respiratory rate from 18 to 12 and 6 breaths/min. Plateau airway pressure decreased by approximately 2 cm H2O (25.4 +/- 2.8 vs. 23.3 +/- 2.6 cm H2O, p <.01) when respiratory rate was decreased from 18 to 12 breaths/min (increase in expiratory time 1.7 secs) and by a similar amount (23.3 +/- 2.6 vs. 21.3 +/- 2.9 cm H2O, p <.01) when respiratory rate was decreased from 12 to 6 breaths/min (increase in expiratory time 5 secs). Peak airway pressure was similar at the three respiratory rates (66.8 +/- 8.7 vs. 66.4 +/- 9.5 vs. 67.8 +/- 11.1 cm H2O at 18, 12, and 6 breaths/min, respectively). End-expiratory flow rates (n = 7) were 61.4 +/- 12.6, 38.6 +/- 4.5, and 23.1 +/- 5.8 mL/sec at respiratory rates of 18, 12, and 6 breaths/min, respectively. Prolongation of expiratory time decreases dynamic hyperinflation in patients with status asthmaticus, as evidenced by a reduction in plateau airway pressure, but the magnitude of this effect is relatively modest when baseline minute ventilation is < or = 10 L/min, because of the low end-expiratory flow rates. Since flow progressively decreases throughout expiration, the reduction in dynamic hyperinflation resulting from a given prolongation of expiratory time will depend on the baseline respiratory rate (i.e., less reduction in dynamic hyperinflation at a lower respiratory rate). Changes in peak airway pressure may not always reflect the changes in dynamic hyperinflation that result from prolongation of expiratory time.

Mixed-effects Modeling of the Intrinsic Ventilatory Depressant Potency of Propofol in the Non-steady State

Despite the ubiquitous use of propofol for anesthesia and conscious sedation and numerous publications about its effect, a pharmacodynamic model for propofol-induced ventilatory depression in the non-steady state has not been described. To investigate propofol-induced ventilatory depression in the clinically important range (at and below the metabolic hyperbola while carbon dioxide is accumulating because of drug-induced ventilatory depression), the authors applied indirect effect modeling to Paco2 data at a fraction of inspired carbon dioxide of 0 during and after administration of propofol. Ten volunteers underwent determination of their carbon dioxide responsiveness by a rebreathing design. The parameters of a power function were fitted to the end-expiratory carbon dioxide and minute ventilation data. The volunteers then received propofol in a stepwise ascending pattern with use of a target-controlled infusion pump until significant ventilatory depression occurred (end-tidal pressure of carbon dioxide > 65 mmHg and/or imminent apnea). Thereafter, the concentration was reduced to 1 microg/ml. Propofol pharmacokinetics and the Paco2 were determined from frequent arterial blood samples. An indirect response model with Bayesian estimates of the pharmacokinetics and carbon dioxide responsiveness in the absence of drug was used to describe the Paco2 time course. Because propofol reduces oxygen requirements and carbon dioxide production, a correction factor for propofol-induced decreasing of carbon dioxide production was included. The following pharmacodynamic parameters were found to describe the time course of hypercapnia after administration of propofol (population mean and interindividual variability expressed as coefficients of variation): F (gain of the carbon dioxide response), 4.37 +/- 36.7%; ke0, CO2, 0.95 min-1 +/- 59.8%; baseline Paco2, 40.9 mmHg +/- 12.8%; baseline minute ventilation, 6.45 l/min +/- 36.3%; kel, CO2, 0.11 min-1 +/- 34.2%; C50,propofol, 1.33 microg/ml +/- 49.6%; gamma, 1.68 +/- 21.3%. Propofol at common clinical concentrations is a potent ventilatory depressant. An indirect response model accurately described the magnitude and time course of propofol-induced ventilatory depression. The indirect response model can be used to optimize propofol administration to reduce the risk of significant ventilatory depression.

A model of the ventilatory depressant potency of remifentanil in the non-steady state.

The C50 of remifentanil for ventilatory depression has been previously determined using inspired carbon dioxide and stimulated ventilation, which may not describe the clinically relevant situation in which ventilatory depression occurs in the absence of inspired carbon dioxide. The authors applied indirect effect modeling to non-steady state Paco2 data in the absence of inspired carbon dioxide during and after administration of remifentanil. Ten volunteers underwent determination of carbon dioxide responsiveness using a rebreathing design, and a model was fit to the end-expiratory carbon dioxide and minute ventilation. Afterwards, the volunteers received remifentanil in a stepwise ascending pattern using a computer-controlled infusion pump until significant ventilatory depression occurred (end-tidal carbon dioxide [Peco2] > 65 mmHg and/or imminent apnea). Thereafter, the concentration was reduced to 1 ng/ml. Remifentanil pharmacokinetics and Paco2 were determined from frequent arterial blood samples. An indirect response model was used to describe the Paco2 time course as a function of remifentanil concentration. The time course of hypercarbia after administration of remifentanil was well described by the following pharmacodynamic parameters: F (gain of the carbon dioxide response), 4.30; ke0 carbon dioxide, 0.92 min-1; baseline Paco2, 42.4 mmHg; baseline minute ventilation, 7.06 l/min; kel,CO2, 0.08 min-1; C50 for ventilatory depression, 0.92 ng/ml; Hill coefficient, 1.25. Remifentanil is a potent ventilatory depressant. Simulations demonstrated that remifentanil concentrations well tolerated in the steady state will cause a clinically significant hypoventilation following bolus administration, confirming the acute risk of bolus administration of fast-acting opioids in spontaneously breathing patients.

Neonatal Exposure to 65% Oxygen Durably Impairs Lung Architecture and Breathing Pattern in Adult Mice

To test the hypothesis that exposure to hyperoxia during the postnatal period of rapid alveolar multiplication by septation would cause permanent impairments, even with moderate levels of hyperoxia. We exposed mouse pups to 65% O(2) (hyperoxic mice) or normoxia (normoxic mice) during their first postnatal month, and we analyzed lung histology, pulmonary mechanics, blood gas, and breathing pattern during normoxia or in response to chemical stimuli in adulthood, when they reached 7 to 8 months of postnatal age. Hyperoxic mice had fewer and larger alveoli than normoxic mice (number of alveoli per unit surface area of parenchyma, 266 +/- 62/mm(2) vs 578 +/- 77/mm(2), p < 0.0001) [mean +/- SD], the cause being impaired alveolarization (radial alveolar count, 5.8 +/- 0.2 in hyperoxic mice vs 10.5 +/- 0.5 in normoxic mice, p < 0.0001). Respiratory system compliance was higher in hyperoxic mice (0.098 +/- 0.006 mL/cm H(2)O) than in normoxic mice (0.064 +/- 0.006 mL/cm H(2)O, p < 0.016). Baseline tidal volume (VT) and breath duration (TTOT]) measured noninvasively by whole-body plethysmography were larger in hyperoxic mice than in normoxic mice (VT, + 15%, p < 0.01; TTOT, + 12%, p < 0.01). Despite these impairments, blood gas, baseline minute ventilation E, and E responses to hypoxia and hypercapnia were normal in hyperoxic mice, compared with normoxic mice. Hyperoxic exposure during lung septation in mice may cause irreversible lung injury and breathing pattern abnormalities in adulthood at O(2) concentrations lower than previously thought. However, ventilatory function and body growth were preserved, and ventilatory function showed no major abnormalities, at least at rest, despite early oxygen-induced injuries.

The impact of insulin-dependent diabetes on ventilatory control in the mouse.

Insulin-dependent diabetes mellitus (IDDM) can lead to ventilatory depression and decreased sensitivity to hypercapnia. We examined relationships between ventilation, plasma insulin, leptin, ketones, and blood glucose levels in two mouse models of IDDM: (1) streptozotocin-induced diabetes in C57BL/6J mice on a regular diet or with induced obesity from a high fat diet; and (2) spontaneous diabetes mellitus in NOD-Ltj mice. In both mouse models, IDDM resulted in depression of the hypercapnic ventilatory response (HCVR). This ventilatory depression was not associated with decreases in plasma insulin or leptin levels. There was, however, a strong association between the duration of hyperglycemia, the decline in HCVR, and increased glycosylation of the diaphragm. Hyperventilation was observed in only six of 14 C57BL/6J obese wild-type mice, despite a significant degree of diabetic ketoacidosis (DKA) in all 14 animals. In mice with DKA, there was a significant correlation between the increase in baseline minute ventilation (V E) and hyperleptinemia (r = 0.77, p < 0.01). In leptin-deficient C57BL/6J-Lep(ob) mice, low levels of both V E and ketones were observed. These results suggest that: (1) depression of the HCVR in IDDM is associated with hyperglycemia and glycosylation of the diaphragm; and (2) the hyperventilation of DKA is leptin dependent.

Isocapnic hyperventilation increases carbon monoxide elimination and oxygen delivery.

Hyperventilation with mixtures of O2 and CO2 has long been known to enhance carbon monoxide (CO) elimination at low HbCO levels in animals and humans. The effect of this therapy on oxygen delivery (DO2) has not been studied. Isocapnic hyperventilation utilizing mechanical ventilation may decrease cardiac output and therefore decrease DO2 while increasing CO elimination. We studied the effects of isocapnic hyperventilation on five adult mechanically ventilated sheep exposed to multiple episodes of severe CO poisoning. Five ventilatory patterns were studied: baseline minute ventilation (RR. VT), twice (2. RR) and four times (4. RR) baseline respiratory rate, and twice (2. VT) and four times (4. VT) baseline tidal volume. The mean carboxyhemoglobin (HbCO) washout half-time (t1/2) was 14.3 +/- 1.6 min for RR. VT, decreasing to 9.5 +/- 0.9 min for 2. RR, 8.0 +/- 0.5 min for 2. VT, 6.2 +/- 0.5 min for 4. RR, and 5.2 +/- 0.5 min for 4. VT. DO2 was increased during hyperventilation compared with baseline ventilation for 2. VT, 4. RR, and 4. VT ventilatory patterns. Isocapnic hyperventilation, in our animal model, did not alter arterial or pulmonary blood pressures, arterial pH, or cardiac output. Isocapnic hyperventilation is a promising therapy for CO poisoning.

Efficacy and Compliance With Noninvasive Positive Pressure Ventilation in Patients With Chronic Respiratory Failure

Previous studies have shown the acute effects of noninvasive positive pressure ventilation (NPPV) in chronic respiratory failure; however, information on the chronic effects of NPPV is limited. We examined the acute and chronic effects of NPPV on gas exchange, functional status, and respiratory mechanics in patients with chronic respiratory failure related to restrictive ventilatory disorders or COPD. Descriptive analysis of prospectively collected clinical data. Inpatient noninvasive respiratory care unit and outpatient clinic of university hospital. Forty patients with chronic respiratory failure (20 with severe COPD and 20 with restrictive ventilatory disorders). All patients were admitted to a noninvasive respiratory care unit for 20 +/- 3 days for inpatient evaluation consisting of medical treatment, rehabilitation, and NPPV evaluation and instruction. NPPV was titrated via a ventilatory support system (BiPAP; Respironics Inc; Monroeville, PA) or a portable volume ventilator (PLV 102; Lifecare, Inc; Boulder, CO) to achieve a > or = 20% increase in baseline minute ventilation while monitoring gas exchange, expired volume, and clinical evidence of a decrease in the patient's work of breathing. The patients' mean age (+/- SD) was 65 +/- 9.7 years, and there was a 3:1 female:male predominance. In the noninvasive respiratory care unit, 36 patients used NPPV for 7.31 +/- 0.26 h/night. Four patients (three with COPD, one with restrictive disorder) withdrew from the study during the 3-week inpatient stay because they could not tolerate NPPV. Six patients (5 with COPD, 1 with restrictive disorder) used a portable volume ventilator and 34 patients used BiPAP (15 with COPD, 19 with restrictive disorders). At discharge, compared with at admission, daytime PaO2/fraction of inspired oxygen (FIO2) increased (327 +/- 10 vs 283 +/- 13 mm Hg; p = 0.01), PaCO2 was reduced (52 +/- 2 vs 67 +/- 3 mm Hg; p = 0.0001), and functional score increased (4.76 +/- 1.16 vs 2.7 +/- 1.64 arbitrary units (AUs); p < 0.01). Six months after discharge, improvements in PaO2/FIO2 (317 +/- 10 vs 283 +/- 13; p = 0.05), PaCO2 (52 +/- 2 vs 67 +/- 3 mm Hg; p = 0.0001), and functional score (5.66 +/- 0.41 vs 2.7 +/- 0.3 AUs; p < 0.001) were maintained compared with admission values. FVC, FEV1, and maximum inspired and expired mouth pressures were unchanged before and after long-term NPPV. Ten patients (7 with COPD, 3 with restrictive disorders) discontinued NPPV at 6 months, and 3 progressed to tracheostomy. The remaining 26 patients continued to use NPPV at the 6-month follow-up. They claimed to use NPPV for 7.23 +/- 0.24 h/night, but logged metered use was 4.5 +/- 0.58 h/night. Problems that required adjustment in either the mask (36%) or ventilator source (36%) included mask leaks (43%), skin irritation (22%), rhinitis (13%), aerophagia (13%), and discomfort from mask headgear (7%). NPPV acutely and chronically improves gas exchange and functional status in patients with chronic respiratory failure, but a significant number of patients do not tolerate NPPV on a chronic basis. Comprehensive follow-up is required to correct problems with NPPV and ensure optimal patient compliance.

Determination of low blood flow limits for arteriovenous carbon dioxide removal.

Arteriovenous carbon dioxide removal (AVCO2R) has been shown to achieve total carbon dioxide (CO2) exchange. To determine optimal blood and gas flow parameters that can provide maximal gas exchange and evaluate the utility of AVCO2R at reduced blood flow, the authors used a low resistance membrane gas exchanger within an arteriovenous shunt in mechanically ventilated sheep. Adult female sheep (n = 5) were anesthetized and underwent placement of the gas exchange device in a simple arteriovenous shunt created between the carotid artery and common jugular vein. CO2 removal was determined as the product of the sweep gas flow (100% oxygen) and its exhaust CO2 content. Gas and blood flow were varied independently, and incremental reductions in minute ventilation (MV) were made while maintaining normocapnia. At maximally reduced ventilator settings, stepwise reductions in blood flow were made to determine the resultant changes in arterial PaCO2 at a sweep gas flow of 3 L/min. CO2 removal increased proportionally to blood flow to a maximum of 1,417 +/- 26 ml/min (19% of cardiac output) and gas flow to 3 L/min. Normal PaO2 and PaCO2 could be maintained with minimal ventilator support (MV = 16% baseline MV) at a blood flow of 500 ml/min or higher. At these maximally reduced ventilator settings, moderate hypercapnia (PaCO2 < or = 75 mmHg) resulted only when blood flow was decreased to below 500 ml/min. Optimizing AVCO2R blood and gas flow maximizes CO2 removal and allows a significant reduction in minute ventilation. In cases of severely limited blood flow, lung rest can still be realized at moderate hypercapnia. At flow rates achievable by percutaneous access, extracorporeal AVCO2R can be used to achieve lung rest during mechanical ventilation.

Decreased Carbon Dioxide Sensitivity in Infants of Substance-Abusing Mothers

To determine whether there is a demonstrable abnormality in control of breathing in infants of substance-abusing mothers during the first few days of life. We enrolled 12 drug-free control infants and 12 infants of substance abusing mothers (ISAMs). These infants experienced otherwise uncomplicated term pregnancies and deliveries. The infants were assigned to a group based on the results of maternal histories and maternal and infant urine toxicology screens. Studies were performed during quiet sleep during the first few days of life. We measured heart rate, oxygen saturations via a pulse oximeter, end-tidal carbon dioxide (ET-CO2) level, respiratory rate, tidal volume, and airflow. The chemoreceptor response was assessed by measuring minute ventilation and the ET-CO2 level after 5 minutes of breathing either room air or 4% carbon dioxide. The gestational ages by obstetrical dating and examination of the infants were not different, although birth weights and birth lengths were lower in the group of ISAMs. Other demographic data were not different, and there were no differences in the infants' median ages at the time of study or in maternal use of tobacco and alcohol. The two groups had comparable baseline (room air) ET-CO2 levels, respiratory rates, tidal volumes, and minute ventilation. When compared with the group of ISAMs, the drug-free group had markedly increased tidal volume and minute ventilation on exposure to 4% carbon dioxide. These increases accounted for the difference in sensitivity to carbon dioxide, calculated as the change in minute ventilation per unit change in ET-CO2 (milliliters per kg/min per mm Hg). The sensitivity to carbon dioxide of control infants was 48.66 +/- 7.14 (mean +/- SE), whereas that of ISAMs was 16.28 +/- 3.14. These data suggest that ISAMs are relatively insensitive to challenge by carbon dioxide during the first few days of life. We speculate that this reflects an impairment of the chemoreceptor response.

Response to added dead space in ventilated preterm neonates and outcome of trial of extubation.

The ventilatory response to an added external dead space was assessed in preterm babies, recovering from respiratory distress syndrome, immediately prior to extubation. All babies were ready for extubation as defined by routine clinical criteria. Baseline measurements of respiratory rate, tidal volume, and minute ventilation were made over a 2 min period using a computerized system consisting of a pneumotachometer connected directly to the proximal end of the endotracheal tube. The measurements were repeated after addition of an external dead space equivalent to 2 anatomical dead spaces (4.4 mL/kg body weight). Thirty-four babies were studied on 40 occasions. Twenty-four infants (60%) were successfully extubated and 16 (40%) required reintubation. Infants in the success and failure groups were matched for gestation at birth, postconceptional age and weight at the time of study, maximum ventilatory requirements, and treatment with methylxanthines. The added external dead space resulted in an increase in minute ventilation in 38 out of the 40 studies. Extubation success and failure groups were compared by expressing the minute ventilation after addition of the external dead space as a percentage of the baseline minute ventilation (%MV1). Successful extubation was associated with a higher median %MV1 compared with babies who failed extubation (156; range, 89.3 to 230; compared to 131; range, 75.2 to 165; P = 0.006). This test may be useful in deciding which babies could be successfully extubated.

Influence of airway resistance on hypoxia-induced periodic breathing.

We studied the effects of changing upper airway pressure on the variability of the dynamic response of ventilation to a hypoxic disturbance in 11 spontaneously breathing dogs. Supralaryngeal pressure, instantaneous inspiratory flow, end-expiratory lung volume, and the inspiratory and expiratory O2 and CO2 concentrations were continuously recorded at baseline and after a 1.5-min hypoxic stimulus (abrupt normoxic recovery). Arterial blood gases were obtained at baseline, at the end of the hypoxic period, and after 1 min of recovery. Airway resistances were modified during the recovery by changing the composition of the inspired gas (all with an inspiratory O2 fraction of 20.9%) among four different trials: two trials were realized with air (density 1.12 g/l), and the other two were with He or SF6 (respective density 0.42 and 4.20) in random order. There was no difference between baseline minute ventilation, arterial blood gases, and supralaryngeal resistance values preceding the trials. The hypoxemic and hypocapnic levels and the hypoxia-induced hyperventilation reached during the hypoxic tests were identical for the different hypoxic stimuli. The supralaryngeal resistance measured at peak flow was dramatically influenced by the composition of the inspired gas: 8.8 +/- 1.8 and 6.9 +/- 1.7 (SE) cmH2O.l-1.s with air, 7.2 +/- 2.2 with He, 21.9 +/- 5.5 with SF6 (P less than 0.05). Ventilatory fluctuations were consistently seen during the posthypoxic period. They were characterized by a strength index value (M) (Waggener et al. J. Appl. Physiol. 56: 576-581, 1984).(ABSTRACT TRUNCATED AT 250 WORDS)

Influences of gender and sex hormones on hypoxic ventilatory response in cats

Hypoxic ventilatory response (HVR) is known to be increased by female as well as male sex hormones, but whether there are differences in HVR between men and women remains unclear. To determine whether gender differences exist in HVR, we undertook systematic comparisons of resting ventilation and HVR in awake male and female cats. Furthermore to explore the potential contribution of sex hormones to gender differences observed, we compared neutered and intact cats of both sexes. Resting ventilation differed among the four groups, but differences disappeared with correction for body weight. Intact females had a lower end-tidal PCO2 than intact male cats (females: 31.6 +/- 0.4 Torr vs. males: 33.6 +/- 0.4 Torr, P less than 0.05), indicating an increased alveolar ventilation per unit CO2 production. HVR expressed as the shape parameter A was similar among the four groups of animals. However, baseline (hyperoxic; end-tidal PO2 greater than 200 Torr) minute ventilation [VI(PO2 greater than 200)] differed among the groups. Therefore we normalized HVR by dividing the shape parameter A by VI(PO2 greater than 200) to compare the relative hypoxic chemosensitivity among the various groups of animals. In addition, we further normalized HVR for body weight, because body size influences ventilation.(ABSTRACT TRUNCATED AT 250 WORDS)

A management option for leaking endotracheal tube cuffs: use of lidocaine jelly

Study Objective: To evaluate the effectiveness of methods for sealing a small endotracheal tube cuff perforation. Design: Randomized evaluation in an in vitro model of mechanical ventilation. In addition, two pertinent cases are reported. Setting: Operative anesthesia service in a large tertiary referral center. Interventions: A transparent acrylic “trachea” attached to a rubber breathing bag (“lung”) was intubated with an 8.0 mm endotracheal tube. Positive pressure mechanical ventilation was begun and baseline minute ventilation recorded. After equilibrium, the endotracheal tube cuff was perforated in a standard fashion, and one of four “treatments” was applied in random sequence. Group A endotracheal tubes (n = 7) were managed by increasing fresh gas flow and manually injecting air into the cuff. Group B cuffs (n = 8) were insuff fated with oxygen to maintain cuff pressure at 25 to 28 mmHg. In Groups C (n = 8) and D (n = 9), an 8 ml mixture of 2% lidocaine hydrochloride jelly ()ylocaine R Astra, Westborough, MA), and saline was injected into the cuff at a dilution of 1:3 and 1:1, respectively. Measurements and Main Results: Measurements included minute ventilation, airway pressure, and intracuff pressure. During the 30-minute observation period after cuff perforation, total exhaled ventilation was assessed and wasted ventilation calculated. Group A wasted ventilation (means ± SD) was significantly greater (112 ± 20 liters, p < 0.01) than Groups B, C, and D (12 ± 12 liters, 10 ± 5 liters, and 18 ± 13 liters, respectively). In Group A, it was impossible to maintain adequate minute ventilation. To remain inflated, Group B cuffs required insufflation at a rate of 10 to 80 ml/min. Groups C and D maintained an excellent cuff seal, but 2 of 9 Group D cuffs could not be deflated, while all Group C cuffs were def latable. Also reported are two cases of persistent intraoperative endotracheal tube cuff leaks refractory to conventional management. Inflation of the endotracheal tube cuff with a lidocaine jelly-saline mixture successfully eliminated the leak, allowing completion of the procedure without reintubation. Conclusions: The authors' in vitro results, in conjunction with the observations from their two cases, suggest that lidocaine jelly mixed with 1 to 3 parts normal saline may be useful in managing certain types of endotracheal tube cuff incomplete.