Volume guarantee ventilation during surgical closure of patent ductus arteriosus.

BACKGROUND: Surgical closure of patent ductus arteriosus (PDA) is associated with adverse outcomes. Surgical exposure requires retraction of the lung, resulting in decreased aeration and compliance. Optimal respiratory support for PDA surgery is unknown. Experience with volume guarantee (VG) ventilation at our institution led us to hypothesize that surgery would be better tolerated with automatic adjustment of pressure by VG to maintain tidal volume (VT) during retraction. OBJECTIVE: The objective of this study was to describe ventilator support, VT, and oxygenation of infants supported with VG during PDA surgery. DESIGN/METHODS: Ventilator variables, oxygen saturation, and heart rate were recorded during PDA surgery in a convenience sample of infants during PDA closure on VG. Pressure limit increased 11% and set VT was 26% lower during lung retraction. Fentanyl and pancuronium/vecuronium were used for anesthesia/muscle relaxation. Longitudinal data were analyzed by analysis of variance for repeated measures. RESULTS: Seven infants, 25.4 ± 1.5 weeks and 723 ± 141 g, underwent closure of PDA on VG at a mean age 29.9 days. No air leak, bradycardia, or death occurred. Target VT was maintained with a modest increase in inflation pressure. Oxygenation remained adequate. CONCLUSIONS: VG avoided hypoxemia and maintained adequate VT with only a modest increase in peak inflation pressure and thus may be a useful mode during PDA surgery.

The comparison of spontaneous breathing and muscle paralysis in two different severities of experimental lung injury.

OBJECTIVES: The benefits of spontaneous breathing over muscle paralysis have been proven mainly in mild lung injury; no one has yet evaluated the effects of spontaneous breathing in severe lung injury. We investigated the effects of spontaneous breathing in two different severities of lung injury compared with muscle paralysis. DESIGN: Prospective, randomized, animal study. SETTING: University animal research laboratory. SUBJECTS: Twenty-eight New Zealand white rabbits. INTERVENTIONS: Rabbits were randomly divided into the mild lung injury (surfactant depletion) group or severe lung injury (surfactant depletion followed by injurious mechanical ventilation) group and ventilated with 4-hr low tidal volume ventilation with spontaneous breathing or without spontaneous breathing (prevented by a neuromuscular blocking agent). Inspiratory pressure was adjusted to control tidal volume to 5-7 mL/kg, maintaining a plateau pressure less than 30 cm H2O. Dynamic CT was used to evaluate changes in lung aeration and the regional distribution of tidal volume. MEASUREMENTS AND RESULTS: In mild lung injury, spontaneous breathing improved oxygenation and lung aeration by redistribution of tidal volume to dependent lung regions. However, in severe lung injury, spontaneous breathing caused a significant increase in atelectasis with cyclic collapse. Because of the severity of lung injury, this group had higher plateau pressure and more excessive spontaneous breathing effort, resulting in the highest transpulmonary pressure and the highest driving pressure. Although no improvements in lung aeration were observed, muscle paralysis with severe lung injury resulted in better oxygenation, more even tidal ventilation, and less histological lung injury. CONCLUSIONS: In animals with mild lung injury, spontaneous breathing was beneficial to lung recruitment; however, in animals with severe lung injury, spontaneous breathing could worsen lung injury, and muscle paralysis might be more protective for injured lungs by preventing injuriously high transpulmonary pressure and high driving pressure.

[Influence of the agents which maintain the coordination between spontaneous breathing and mechanical ventilation on haemodynamics and respiration].

OBJECTIVE: To investigate the haemodynamic and respiratory changes following intravenous administration with midazolam, pavulon or both of them in the patients having incoordination between spontaneous breathing and mechanical ventilation. METHODS: Thirty patients having incoordination between spontaneous breathing and mechanical ventilation were randomly assigned to receiving intravenous injection of pavulon (group 1), midazolam (group 3), and both (group 2) respectively with 10 cases in each group. The degree of coordination between spontaneous breathing and mechanical ventilation, blood pressure (BP), heart rate (HR), respiration frequency (RF), oxygen saturation of pulse (SpO(2)) were observed before the medication and at 5, 15, 30 and 60 minutes following the administration of drugs in all the patients. RESULTS: Incoordination between spontaneous breathing and mechanical ventilation, fast RF, decreased SpO(2) were observed before the drug in all patients. Improvement of respiratory was significant in group 2. Patients in group 2 were in excellent coordination between spontaneous breathing and mechanical ventilation, reaching 100% within 30 minutes after administration, and lasting longer. The haemodynamics maintained stable and a significant improvement in respiration and SpO(2) were found. BP and HR were elevated significantly, and RF and hypoxemia were improved, and the degree of coordination between spontaneous breathing and mechanical ventilation reached 100% 5 minutes after the drug, but with shorter duration in group 1. There were no obvious changes in BP, HR, RF and hypoxemia, and the degree of coordination between spontaneous breathing and mechanical ventilation was lowest in group 3. CONCLUSION: The combined use of midazolam and pavulon has little influence on circulation, and it also can maintain the coordination between spontaneous breathing and mechanical ventilation. It is suggested that the combined use of midazolam and pavulon is an optimal way to improve the ventilatory function in mechanical ventilation.

Neuromuscular paralysis for newborn infants receiving mechanical ventilation.

BACKGROUND: Ventilated newborn infants breathing in asynchrony with the ventilator are at risk for complications during mechanical ventilation, such as pneumothorax or intraventricular hemorrhage, and are exposed to more severe barotrauma, which consequently could impair their clinical outcome. Neuromuscular paralysis, which eliminates spontaneous breathing efforts of the infant, has potential advantages in this respect. However, a number of complications have been reported with muscle relaxation in infants, so that concerns exist regarding the safety of prolonged neuromuscular paralysis in newborn infants. OBJECTIVES: To determine whether routine neuromuscular paralysis of newborn infants receiving mechanical ventilation compared with no routine paralysis results in clinically important benefits or harms. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2004), MEDLINE (from 1966 to April 2004) and EMBASE (from 1988 to April 2004) were searched. References of review articles were hand searched. Language restriction was not imposed. SELECTION CRITERIA: All trials using random or quasi-random patient allocation, in which the routine use of neuromuscular blocking agents during mechanical ventilation was compared to no paralysis or selective paralysis in newborn infants. Methodological quality was assessed blindly and independently by the two authors. DATA COLLECTION AND ANALYSIS: Data were abstracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with independent evaluation of trial quality, and abstraction and synthesis of data by both authors. Treatment effect was analysed using relative risk, risk difference and weighted mean difference. MAIN RESULTS: Ten possibly eligible trials were identified, of which six were included in the review. All the included trials studied preterm infants ventilated for respiratory distress syndrome, and used pancuronium as the neuromuscular blocking agent. In the analysis of the results of all trials, no significant difference was found in mortality, air leak or chronic lung disease, but there was a significant reduction in intraventricular hemorrhage and a trend towards less severe intraventricular hemorrhages. In the subgroup analysis of trials studying a selected population of ventilated infants with evidence of asynchronous respiratory efforts, a significant reduction in intraventricular hemorrhage (any grade and severe IVH) was found, and a trend towards less air leak. In the subgroup analysis of trials studying an unselected population of ventilated infants, no significant differences were found for any of the outcomes. AUTHORS' CONCLUSIONS: For ventilated preterm infants with evidence of asynchronous respiratory efforts, neuromuscular paralysis with pancuronium seems to have a favourable effect on intraventricular hemorrhage and possibly on air leak. Uncertainty remains, however, regarding the long term pulmonary and neurologic effects, and regarding the safety of prolonged use of pancuronium in ventilated newborn infants. There is no evidence from randomized trials on the effects of neuromuscular blocking agents other than pancuronium. The routine use of pancuronium or any other neuromuscular blocking agent in ventilated newborn infants cannot be recommended based on current evidence.

Improved oxygenation after muscle relaxation in adult respiratory distress syndrome.

Arterial blood oxygenation improved repeatedly after sedation and paralysis in a 27-year-old woman requiring mechanical ventilation for the adult respiratory distress syndrome. Oxygen consumption and cardiac output decreased proportionately after paralysis so that the partial pressure of oxygen in mixed venous blood remained unchanged. Paralysis eliminated inspiratory distortion of the airway pressure waveform and prevented forceful use of expiratory musculature. A flow-related reduction of venous admixture or recruitment of lung volume may best explain the beneficial effect of muscle relaxation on arterial saturation.

Are venous circulatory abnormalities important in the pathogenesis of hemorrhagic and/or ischemic cerebral injury?

The venous circulatory changes in 12 intubated premature infants with fluctuations or elevations in arterial BP were studied. The objectives of the study were to determine whether important alterations in venous pressure occur in infants with fluctuations in arterial BP or with elevations in arterial BP associated with suctioning. Venous and arterial catheters were present in all infants. Perfusion pressure was derived from the difference between mean arterial BP and venous pressure. At rest, minimal change in arterial BP, venous pressure, and perfusion pressure was observed. Elevations in arterial BP were accompanied by pronounced changes in venous pressure. However, because the magnitude and the direction of the changes in venous pressure were not consistent, pronounced changes in perfusion pressure resulted. Fluctuations in arterial BP were associated with fluctuations in venous pressure, which also resulted in pronounced and continuous alterations in perfusion pressure. Induced muscle paralysis in two infants obliterated the changes in arterial BP, venous pressure, and perfusion pressure associated with suctioning. These data demonstrate that marked venous circulatory changes accompany common arterial circulatory abnormalities; such alterations on the venous side of the circulation may be important in the pathogenesis of neonatal hemorrhagic and/or ischemic injury.

Blood pressure fluctuation and intraventricular hemorrhage in the preterm infant of less than 31 weeks' gestation.

A total of 22 infants of less than 31 weeks' gestation who were mechanically ventilated for a minimum of 12 hours for respiratory distress syndrome were studied. The coefficient of variation of direct systolic pressure was measured each minute from six to 36 hours of age and averaged per hour after birth with a microcomputer-based system of data collection. At the start of recording, the ultrasound scan appeared normal in each infant, but intraventricular hemorrhage developed in ten infants less than 36 hours of age. Twelve infants remained free of intraventricular hemorrhages. BP fluctuation was greater for a longer proportion of measured time in infants in whom intraventricular hemorrhage did not develop compared with those in whom it did develop P less than .05). These findings do not support a causal relationship between BP fluctuation and intraventricular hemorrhage within the range of coefficient of variation studied.

Controlled evaluation of muscle relaxation in the ventilated neonate.

To assess the effects of muscle relaxation on the critically ill ventilated neonate, pancuronium bromide was administered for a 12-hour period to ten low-birth-weight neonates (960 to 2,000 gm) of 26 to 34 weeks gestation, all whom required mechanical ventilation and were studied within 48 hours of birth (six to 39 hours). The infants were also studied for a 12-hour period during which no pancuronium bromide was administered. During both study periods, the order of which was randomized, heart rate, blood pressure, PO2, and intracranial pressure were continuously measured. The amounts of handling during the pancuronium and control periods were similar. The results revealed a significantly greater duration of hypoxia (PO2 less than 50 torr) (56.1 vs 23.6 minutes, P less than .001) and hyperoxia (PO2 greater than 70 torr) during the control period (92.5 vs 13 minutes, P less than .001). Durations of intracranial pressure elevation 10 cm H2O above the infant's baseline were significantly less during paralysis (6.7 vs 58.8 minutes, P less than .001) as were spikes of intracranial pressure to greater than 25 cm H2O (1.6 vs 24.4, P less than .05). There was no significant improvement in blood gas values, fractional inspiratory oxygen, or ventilator settings during muscle relaxation. Pancuronium reduced periods of nonoptimal oxygenation and elevated intracranial pressure and may therefore help to decrease adverse sequelae for the low-birth-weight, ventilated neonate.

Aggressive intensive care treatment of very elderly patients with tetanus is justified.

Tetanus is now rare in industrialized countries, occurring mainly in elderly patients. To assess whether aggressive therapy of these patients in the intensive care unit is justified, we retrospectively studied all patients with tetanus hospitalized in our institution between 1968 and 1989. Patients over the age of 70 years fared as well as those under 70 years and recovered without sequelae. These results favor aggressive treatment of elderly patients with tetanus in the intensive care unit.

Measurement of mucociliary transport velocity in ventilated patients. Short-term effect of general anesthesia on mucociliary transport.

OBJECTIVES: The objectives of this study were to evaluate a method for measuring BTV in ventilated patients and to study the short-term effect of general anesthesia with midazolam, Fentanyl, pancuronium and O2:N2O on BTV. DESIGN: The study included phantom measurements on a bronchoscopy model and the determination of BTV in patients in a convenience sample trial. SETTING: The study took place in a university hospital. PATIENTS: Fourteen patients undergoing major abdominal surgery with planned postoperative mechanical ventilation were included in the study. All patients gave their written informed consent to participate in the study. INTERVENTIONS: Bronchial mucus transport velocity was measured with a small volume (0.05 to 0.08 ml) of technetium 99m-labeled albumin microspheres with an activity of 3 MBq. The radiolabeled bolus was deposited on the dorsal mucosal surface at the distal end of the right and left main bronchus via flexible bronchoscopy. The movement of the microspheres toward the trachea was visualized and recorded using a scintillation camera; quantitative evaluation utilized the condensed image. MAIN MEASUREMENTS AND RESULTS: The technique was validated in a bronchoscopy model and in an intubated patient by moving a radioactive drop in a catheter through the main bronchi at velocities from 0 to 20 mm/min. The velocities determined by the image processing technique correlated well with the data by the model and patient determination (right bronchus, r = 1.0; left bronchus, r = 1.0). In seven ventilated patients, mechanical irritation by the fiberscope produced no significant effect on BTV. The BTV was measured preoperatively in seven conscious patients one day before surgery while they received local anesthesia with 10 ml of 1 percent lidocaine and postoperatively while they received intubation anesthesia. The preoperative and postoperative BTV values showed no significant differences (10.5; 5.7 to 13.7 mm/min; vs 9.7 (3.7 to 15.3) (median with range). CONCLUSION: By this method, bronchial transport velocity can be determined in a relatively short time in ventilated patients. General anesthesia with midazolam, Fentanyl, pancuronium and O2:N2O does not influence BTV.

Myopathy following mechanical ventilation for acute severe asthma: the role of muscle relaxants and corticosteroids.

BACKGROUND: Acute myopathy following mechanical ventilation for near-fatal asthma (NFA) has been described recently, and some researchers have suggested that this complication is related to the use of neuromuscular blocking agents (NMBAs) and corticosteroids (CSs). OBJECTIVES: To determine the incidence of acute myopathy in a group of patients and to examine the most important predictors of its development. DESIGN AND METHODS: A retrospective cohort study over a 10-year period (1985 to 1995) of all asthma patients who received mechanical ventilation at two centers in Vancouver (designated center 1 and center 2). RESULTS: In center 1, there were 58 patients who had 64 episodes of NFA, and in center 2, there were 28 patients who had 30 episodes. NMBAs were used in 30 of 86 admissions for acute severe asthma (35%). The mean (+/- SD) duration of muscle paralysis was 3.1+/-2.3 days. A total of 9 patients (10.4%) developed significant myopathy. The incidence of myopathy was 9 of 30 (30%) among patients who received NMBAs. In a multiple logistic regression model, the development of myopathy was only significantly associated with the duration of muscle relaxation. The odds ratio for the development of myopathy increased by 2.1 (95% confidence interval, 1.4 to 3.2) with each additional day of muscle relaxation. The dose and the type of the CS were not significantly associated with the myopathy in the multiple logistic regression analysis. CONCLUSION: Our study showed that there is a high incidence of acute myopathy when NMBAs are used for NFA. The incidence of myopathy increases with each additional day of muscle relaxation.

Neuromuscular disorder in intensive care unit patients treated with pancuronium bromide. Occurrence in a cluster group of seven patients and two sporadic cases, with electrophysiologic and histologic examination.

During six consecutive months, seven patients admitted to our ICU (15 beds, general ICU, approximately 300 intubated patients per year) for acute respiratory failure requiring intubation and mechanical ventilation presented with a peculiar neuromuscular disorder. After the occurrence of this cluster group of patients, we detected two more similar but isolated cases in the following 18 months, ie, altogether 9 patients in 2 years of observation, or 1.55 percent of all intubated patients in our ICU. Sedation was achieved using midazolam, curarization was effected with the neuromuscular non-depolarizing agent pancuronium bromide (PB), and corticosteroids were administered to eight patients. Shortly after discontinuation of sedation and curarization, we observed a persistent tetraparetic syndrome and/or peroneal palsy with a concomitant increase of serum creatine kinase (CK). None of the patients was septic or had the multisystem organ failure. A strong association between CK increase and PB administration was found, whereas no patient suffered severe liver or kidney failure. The duration of the neurologic deficit ranged from 4 to 52 weeks, with only partial recovery for some patients; the duration of dysfunction was apparently related to the total dose of corticosteroids received. Two patients had difficulty being weaned from the respirator and required tracheostomy. Electrophysiologic studies showed signs of axonal neuropathy and myopathic changes, ie, motor units of brief duration, small amplitude, overly abundant for the voluntary effort being exerted. Muscle biopsies showed significant myopathic alterations, with foci of muscle necrosis in most patients and minimal lymphocytic inflammation in one patient. The neurologic complication described differs from the polyneuropathy in critically ill patients. Furthermore, PB or corticosteroids or both appear to be the causal agents. The duration of the neuromuscular dysfunction may be related to concomitant steroid therapy. The CK enzyme seems to be a marker of the disorder. This disorder is associated with myopathic alterations and axonal degeneration in some patients. Pancuronium bromide should be used with caution, particularly when associated with steroids therapy, and it may cause difficulty in weaning patients from the respirator.

The effect of single-dose and continuous skeletal muscle paralysis on respiratory system compliance in paediatric intensive care patients.

OBJECTIVE: To investigate the effect of single dose and continuous skeletal muscle paralysis on respiratory system compliance in 53 paediatric intensive care patients. DESIGN: Prospective clinical study. SETTING: Multidisciplinary paediatric intensive care unit. PATIENTS: Twenty-three children ventilated for acute pulmonary pathology, and 30 ventilated for isolated intracranial pathology, who initially had normal lungs. INTERVENTIONS: The 23 patients with acute pulmonary pathology received a single dose of muscle relaxant to facilitate diagnostic procedures. Fifteen patients with isolated intracranial pathology received continuous skeletal muscle paralysis for longer than 24 h, and the other 15 received no paralysis. MEASUREMENTS AND RESULTS: Respiratory system compliance deteriorated by 14% from 0.519 +/- 0.2 to 0.445 +/- 0.18 ml cmH2O-1 kg-1 (p < 0.001) following a single dose of muscle relaxant in the 23 patients with acute pulmonary pathology. In the 15 with isolated intracranial pathology who received continuous skeletal muscle paralysis there was a progressive deterioration in compliance, which reached 50% of the initial compliance by day 4 of paralysis (p < 0.001) and improved back to normal following discontinuation of paralysis. There were no changes in compliance in the 15 patients with isolated intracranial pathology who were ventilated but not paralysed. The paralysed patients required mechanical ventilation longer than the non-paralysed patients (p < 0.001), and 26% of these patients developed nosocomial pneumonia (p = 0.03), a complication that was not seen in the non-paralysed patients. CONCLUSIONS: Skeletal muscle paralysis results in immediate and progressive deterioration of respiratory system compliance and increased incidence of nosocomial pneumonia. The benefits of paralysis should be balanced against the risks of deteriorating pulmonary function.

Comparison of atracurium and pancuronium in mechanically ventilated neonates.

OBJECTIVE: To compare haemodynamic and gas exchange effects after either atracurium or pancuronium given to ventilated neonates with respiratory failure. DESIGN: In this prospective study neonates were alternately assigned to receive either atracurium or pancuronium, intravenously. SETTING: Paediatric and neonatal ICU in a teaching hospital. PATIENTS: 21 ventilated neonates with mean birth weight of 2293 g, suffering from respiratory distress syndrome, meconium aspiration syndrome or pneumonia were included in the study. Patients were entered if they were breathing out of phase with the ventilator and required FIO2 > 0.4 and peak inspiratory pressure (PIP) > 15 cm H2O. Exclusion criteria were unstable haemodynamics or a pneumothorax. INTERVENTIONS: Heart rate, respiratory rate, invasive blood pressure and transcutaneous oxygen tension were monitored continuously. IV atracurium (0.3 mg/kg) or pancuronium (0.1 mg/kg) were administered. Arterial blood gas analysis was performed before and 10 min after injection of muscle relaxant. MEASUREMENTS AND RESULTS: Atracurium caused a significant decrease in heart rate (p < 0.05), systolic and mean blood pressure (p < 0.01). There was also a slight decrease in PaO2 and PaCO2 (n.s.). Administration of pancuronium resulted in an increase in heart rate (p < 0.01) and a slight decrease of blood pressure (n.s.). PaCO2 remained unchanged, whereas PaO2 increased slightly (n.s.). The PtcO2 index (PtcO2/PaO2) decreased after atracurium and did not change after pancuronium (both n.s.). With both drugs a slight increase in alveolar to arterial oxygen tension difference was observed (n.s.). There was one episode of hypotension and one of hypoxaemia--both after pancuronium. CONCLUSION: Both drugs may be used for muscle relaxation in neonates with respiratory failure. Atracurium however causes more cardiovascular depression, whereas the effect of pancuronium may be difficult to predict.

Paralysis has no effect on chest wall and respiratory system mechanics of mechanically ventilated, sedated patients.

OBJECTIVE: To evaluate the separate effects of sedation and paralysis on chest wall and respiratory system mechanics of mechanically ventilated, critically ill patients. SETTING: ICU of the University "La Sapienza" Hospital, Rome. PATIENTS AND PARTICIPANTS: 13 critically ill patients were enrolled in this study. All were affected by disease involving both lungs and chest wall mechanics (ARDS in 4 patients, closed chest trauma without flail chest in 4 patients, cardiogenic pulmonary oedema with fluidic overload in 5 patients). MEASUREMENTS AND RESULTS: Respiratory system and chest wall mechanics were evaluated during constant flow controlled mechanical ventilation in basal conditions (i.e. with the patients under apnoic sedation) and after paralysis with pancuronium bromide. In details, we simultaneously recorded airflow, tracheal pressure, esophageal pressure and tidal volume; with the end-inspiratory and end-expiratory airway occlusion technique we could evaluate respiratory system and chest wall elastance and resistances. Lung mechanics was evaluated by subtracting chest wall from respiratory system data. All data obtained in basal conditions (with the patients sedated with thiopental or propofol) and after muscle paralysis were compared using the Student's t test for paired data. The administration of pancuronium bromide to sedated patients induced a complete muscle paralysis without producing significant modification both to the viscoelastic and to the resistive parameters of chest wall and respiratory system. CONCLUSIONS: This study demonstrates the lack of additive effects of muscle paralysis in mechanically ventilated, sedated patients. Also in view of the possible side effects of muscle paralysis, our results question the usefulness of generalized administration of neuromuscular blocking drugs in mechanically ventilated patients.

Centrally driven slow oscillating potential of extrathoracic trachea.

Spontaneous electrical activity of extrathoracic trachea was recorded along with force developed by tracheal smooth muscle and phrenic nerve activity in decerebrated, paralyzed, and artificially ventilated dogs with pneumothorax. The tracheal electrical activity exhibited slow oscillating potentials that were coupled with spontaneous phasic contraction of trachea. Both rhythmic changes were synchronous with central respiratory rhythm represented by phrenic burst, independent of the respirator's rhythm. The dominant component of the slow oscillating potentials consisted of sinusoidal waves with large amplitude that occurred shortly after cessation of phrenic burst, i.e., in the postinspiratory phase. The concomitant small change in the slow oscillating potentials began in the late inspiratory phase just before the initiation of the tracheal contraction. This phase relationship was preserved after removal of intrathoracic vagal afferents from lungs. Such slow oscillating potentials were also observed during lung collapse produced by disconnecting the tube attached to the respirator. Transection of recurrent laryngeal nerves abolished the slow oscillating potentials. These results indicate that the slow oscillating potentials of the extrathoracic trachea are generated by a physiological process associated with the central respiratory rhythm. The dominant component of the slow oscillating potentials occurs in the postinspiratory phase.

Differential effects of pancuronium bromide on cardiopulmonary function in the neonatal lamb.

The effect of pancuronium bromide (Panc Br) on resting cardiopulmonary function and cardiopulmonary responses to intravenous injection of acetylcholine (Ach) and histamine (H) was evaluated in neonatal lambs. The animals were mechanically ventilated and managed to maintain physiologic gas exchange and acid-base conditions. A proximal segment of the cervical trachea was bypassed; the developed pressure response of this segment (P cervical trach) was used as a direct indication of airway smooth muscle contraction and bronchoconstriction. Pulmonary resistance (Rp) and functional residual capacity were determined. The change in Rp from resting values was used as a functional indicator of central and peripheral airway bronchoconstriction. Cardiovascular function and responses were evaluated from changes in mean arterial pressure and heart rate. Following Panc Br, there was a significant reduction in Ach-induced P cervical trach (-50 +/- 9.2% SE) and Rp (-46 +/- 2.4% SE). In contrast, Panc Br did not significantly change Ach-induced bradycardia and hypotension, cardiopulmonary responses to H, and resting cardiopulmonary function. The differential effects of Panc Br on cardiopulmonary function appear to be related to regional differences between cardiovascular and airway smooth muscle muscarinic receptors in the neonate. The results of this study elucidate a mechanism which may explain previously reported variability in the effect of Panc Br on neonatal cardiopulmonary function. Furthermore, the Panc Br-related attenuation of airway smooth muscle responses suggests that this form of neuromuscular blockade affects the regulation of airway tone and may influence the susceptibility of the neonate to airway deformation consequent to mechanical ventilation.

Effect of the respiratory-related bronchial rhythmic constriction on alveolar ventilation in the dog.

The middle-sized bronchus constricts during mid-inspiration through early-expiration. The purpose of this study was to elucidate the physiological role of this respiratory-related bronchial rhythmic constriction (RRBRC). The following parameters were measured in 12 decerebrated and paralyzed dogs: pressure from a balloon-tipped catheter in the fifth-generation bronchus (to reveal RRBRC), efferent neurogram from C(5) phrenic, and ventilatory flow and volume. We found a small but significant reduction of peak expiratory flow of mechanical ventilation during RRBRC. During bilateral vagal cold block, RRBRC was simulated by intermittent electric stimulation of vagal fibers distal to the cold block. This stimulus evoked a decrease in peak expiratory flow and in Pa(CO2) (approximately 1.5 mmHg). After vagal warming, mechanical ventilation was terminated, and blood gases were maintained normal by extracorporeal oxygenation. During each RRBRC ventilatory volume decreased by approximately 3 ml. The changes in gas volume and RRBRC disappeared after bilateral vagotomy. These findings support the concept that the physiological role of RRBRC is to facilitate alveolar gas exchange by reducing expiratory flow, anatomical dead space, or both.