Estimation of respiratory drive with carbon dioxide and helium.

In 21 studies on 15 infants an additional dead space tube produced a significant rise in end-tidal PCO2 and fall in end-tidal PO2, associated with a rise in minute ventilation (228 +/- 77 mL/kg/min at zero, 348 +/- 85 mL/kg/min at one, and 437 +/- 128 mL/kg/min at two anatomical dead spaces). The differences between end-inspiratory and end-expiratory PCO2 and PO2 did not change significantly, suggesting an increase in dead space, but not in alveolar ventilation. In a further 9 babies the rise in ventilation was unchanged when measurements were repeated in 30% oxygen (361 +/- 65 vs. 340 +/- 54 mL/kg/min at one anatomical dead space). Studies on 8 babies, with the added tube ventilated by a fan, showed that a mean 28% of the rise in minute ventilation was due to increased resistance. Although the response to tube breathing in neonates is complex, carbon dioxide appears to be the major factor producing increased ventilation.

In normoxemic cats, acetazolamide (ACTZ) has been shown to cause a large rise in ventilation (VE) but a decrease in peripheral chemoreceptor activity. The relative contribution of the peripheral chemoreceptors to ventilation is higher during hypoxemia than during normoxemia. Therefore, what are the effects of ACTZ during steady-state hypoxemia? The aims of this study in anesthetized cats were 1) to study the effect of ACTZ (50 mg/kg iv) on mean hypoxemic [arterial PO2 (PaO2) approximately 6 kPa] ventilation and 2) to study the effect of ACTZ on the isocapnic hypoxic ventilatory response. In the first study, in six cats with an inspiratory CO2 fraction of 0, ACTZ led to an insignificant rise in mean VE of 119 ml.min-1.kg-1 after 1 h. In five other cats maintained at an inspiratory CO2 fraction of 0.015, ACTZ resulted in a significantly larger response in VE (268 and 373 ml.min-1.kg-1 after 1 and 2 h, respectively). In the second study, before infusion in five cats, an isocapnic fall in mean PaO2 from 13 to 4.7 kPa led to a significant rise in mean VE of 385 ml.min-1.kg-1; 1 h later, the response (at the same mean alveolar PCO2) was reduced to an insignificant rise of 38 ml.min-1.kg-1. Before infusion four other cats showed a significant rise in mean VE of 390 ml.min-1.kg-1 when mean PaO2 was lowered isocapnically from 12.4 to 6.8 kPa; 2 h after infusion, an isocapnic fall in mean PaO2 from 13.9 to 7.2 kPa led to an insignificant rise of 112 ml.min-1.kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

TRACHEAL stenosis is a rare but a life-threatening condition and is caused by congenital problems, postintubation injury, trauma, tracheal tumor, and compression of the trachea by tumor. Although accurate prevalence of this condition is unknown, an incidence of 4.9 cases per million per year is estimated for postintubation tracheal stenosis.1A stenosis commonly occurs at the cuff of the tube (intrathoracic trachea) or at the level of the tracheostomy stoma (extrathoracic trachea).Anesthesia of a patient with tracheal stenosis is challenging for anesthesiologists. Depending on the severity and location of the stenosis and the type of surgical procedure, there may be a variety of choices for perioperative airway management such as a facemask, laryngeal mask airway,2an tracheal intubation tube,3,4cardiopulmonary bypass,5and extracorporeal membrane oxygenation.6The American Society of Anesthesiologists practice guidelines for management of the difficult airway primarily focus airway problems caused at the extrathoracic airway and may not be helpful, particularly for managing patients with intrathoracic tracheal stenosis.7In this case scenario, we present a patient with severe intrathoracic tracheal stenosis, who required surgery for a lumbar fracture in the prone position. Various airway management strategies and the actual management used are discussed.A 38-yr-old obese man (height, 172 cm; weight, 95 kg; body mass index, 32 kg/m2) was scheduled to have a thoracolumbar laminectomy and fixation for a burst fracture of the first lumbar vertebra. Surgery was to be performed in the prone position. The operation duration and blood loss were preoperatively estimated to be 4 h and 500 ml. He had a history of prolonged intubation when he suffered a traumatic brain injury at 8 yr of age. He had epilepsy treated with phenobarbital but had no impairment of neurologic development and was cooperative. Despite undergoing tracheal resection and plasty for severe postintubation tracheal stenosis at 17 yr of age, he had relatively loud inspiratory and expiratory stridor while awake. Spirometry in the sitting position revealed reduced forced expiratory volume in the first second (FEV1= 1.95 l, 53%-predicted) and peak expiratory flow rates (PEF = 180 l/min, 30% predicted). Arterial blood gas analysis indicated mild impairment of oxygenation but normal ventilation (Fio2= 0.2, pH = 7.43, Pao2= 71 mmHg, Paco2= 33 mmHg). A flow-volume loop showed a typical upper airway obstruction pattern (fig. 1). Three-dimensional computed tomography (CT) of the trachea revealed severe intrathoracic tracheal stenosis more than 3 cm in length. In cross-section, the stenotic lesion was elliptical with a minor axis of 0.5 cm and a major axis of 1.5 cm (fig. 2). Despite the tracheal stenosis, he had no dyspnea during daily activities and was otherwise healthy. Nurses in the ward witnessed loud snoring and occasional apnea during sleep. Preoperative airway examination revealed Mallampati class 3, normal thyromental distance, and no limitation of neck or mandible movements. The orthopedic surgeons considered that neither conservative therapy nor surgery with regional anesthesia was appropriate because of his neurologic symptoms and the estimated operational duration and invasiveness of the surgery.Only the preoperative information with the figures described above was initially sent to both Drs. Asai and Cook. They were selected because of their previous reports of similar cases.3,4The following are their airway management plans for this patient.I follow an algorithm for anesthetic management of patients with tracheal stenosis based on its pathophysiology (fig. 3). Although the patient had relatively loud inspiratory and expiratory stridor and apnea during sleep, he had no dyspnea during daily activities. Therefore, I consider that spontaneous breathing or mechanical ventilation is likely to be possible through the stenosis with general anesthesia. Nevertheless, severe airway obstruction may occur during induction of general anesthesia, and thus the appropriate backup method will be required to prevent disaster.There are three possible methods for airway management of this case: (1) the use of a supraglottic airway alone, (2) the use of a supraglottic airway and a tube-exchange catheter, and (3) the use of a supraglottic airway, an endotracheal tube, and a tube-exchange catheter such as Cook Airway Exchange Catheter (Cook Medical, Bloomington, IN; 2.7 mm internal diameter [ID]). The choice of method would depend on both the risks of airway obstruction or dislodgement of the selected airway device and accessibility of the airway for reinsertion of the device.In this case, the airway might be managed with a supraglottic airway alone, but there are two major potential problems with this method: airway obstruction after induction of anesthesia and dislodgement of the supraglottic airway (particularly when the patient is turned to prone position from the supine position). One possible solution is to place the patient in the prone position and insert a supraglottic airway while the patient is still awake, and then induce anesthesia with increasing concentrations of sevoflurane while maintaining spontaneous breathing. Although the presence of the supraglottic airway would prevent airway obstruction above the vocal cords, worsening of the tracheal stenosis and hence severe airway obstruction may develop during inhalational induction with sevoflurane. In such a case, administration of sevoflurane should be terminated and the patient should be woken up. If inadvertent dislodgement of the airway device in the prone position is a risk, safety would be increased by prior insertion of a tube-exchange catheter, because this would enable both the maintenance of oxygenation until reinsertion of the supraglottic airway and the tracheal intubation through it.4,8Alternatively, a more conservative but a safer approach, which I consider the most appropriate in this case, is tracheal intubation with the two backup methods of the use of both a supraglottic airway and a tube-exchange catheter. In this case, the narrowest caliber of the trachea is 5 mm, and thus the largest size of an endotracheal tube, which can be passed through the stenosis, would be 4.0 mm ID, and ventilation may not be sufficient. Therefore, it would be necessary to insert a larger endotracheal tube with its tip proximal to the stenosis. Three-dimensional CT indicates that the stenosis is in the mid to lower trachea, and thus it would only be possible to insert the distal 3-4 cm of the endotracheal tube into the trachea, necessitating backup plans, in case of tube dislodgement. In such an event, either the supraglottic airway or the exchange catheter could then be used for maintaining oxygenation and reinserting the endotracheal tube. I would prepare for jet ventilation through the exchange catheter.After preoxygenation of the patient in the supine position, I would allow the patient to breathe increasing concentrations of sevoflurane in oxygen, and then assist ventilation manually via a facemask. After injection of a neuromuscular blocking agent, I would insert a Cook airway exchange catheter into the trachea under direct laryngoscopy, and then insert either the ProSeal Laryngeal Mask Airway ™ (PLMA ™; Laryngeal Mask Company, Henley-on-Thames, United Kingdom) #5 or i-gel (Intersugical Ltd., Wokingham, Berkshire, United Kingdom), another supraglottic airway, while the exchange catheter is placed outside the supraglottic airway. With the aid of a fiberoptic bronchoscope, I would pass a reinforced endotracheal tube through the supraglottic airway into the trachea so that the tip of the endotracheal tube is approximately 1-2 cm proximal to the stenosis. I would not inflate the endotracheal tube cuff, because it would be positioned at the glottis. Wrapping adhesive tape around the endotracheal tube at the connecter of the supraglottic airway would prevent both dislodgement of the endotracheal tube and gas leakage through the supraglottic airway. I would then adjust the position of the exchange catheter so that its tip is beyond the tracheal stenosis. After the patient is turned to the prone position, I would confirm (using a fiberscope) the appropriate positions of both endotracheal tube and exchange catheter. I would maintain the tidal volume as low as possible allowing hypercapnia to prevent excessive peak airway pressure. When possible, spontaneous breathing would be resumed. After surgery, I would remove the supraglottic airway once the patient has recovered from general anesthesia and is responsive to verbal commands, but would leave the tube exchange catheter in place, until it becomes certain that the patient can maintain a clear airway.This is a truly difficult patient. I would first reiterate to the surgeons that perioperative airway complications are a potential risk to the patient's life. The options of conservative treatment or transfer to a center with facility for combined tracheal reconstructive and trauma surgery must be explicitly considered.Assuming neither is possible I would premedicate the patient with a proton pump inhibitor 12 h before anesthesia. Two experienced anesthetists and an experienced anesthetic assistant would be required and briefed. I would start by placing a narrow gauge cricothyroid cannula specifically a 13-gauge Ravussin cannula (VBM Medizintechnik, Sulz, Germany) with local anesthesia and confirm its position by feeling expired gas, seeing gas exit through a bubble of saline and with capnography. If there was concern about the position of the Ravussin cannula, I would perform awake fiberoptic inspection to confirm its position before proceeding. Next, I would place a PLMA ™. If the patient was cooperative, I would do this during topical anesthesia. If he was not I would place it during general anesthesia. I would preoxygenate the patient fully with continuous positive airway pressure performed with at least 25 degrees head up position to increase lung volumes and maximize the apnea period before hypoxemia develops. I would administer a modest dose of opioid (e.g. , fentanyl 100 μg titrated in > 2-3 min) and propofol by target-controlled infusion. I would start with a low propofol effect site target (1-1.5 μg/ml) and increase this in steps of 0.5 μg/ml for every 1-3 min while maintaining spontaneous ventilation. At the point of eye closure, but before full anesthesia, I would assess ease of assisted ventilation. If ventilation was difficult or impossible, I would abandon this attempt and allow the patient to wake up. After confirmation of adequate mask ventilation, I would then paralyze with rocuronium, increase the depth of anesthesia, and insert a PLMA ™, using a bougie-guided technique.9,10After placement of the PLMA ™, I would then intubate the trachea through it. If the PLMA ™ was placed awake, I would induce anesthesia after PLMA ™ placement. For intubation, I would use a 4.2-mm fiberscope on which an Aintree Intubating Catheter (AIC; Cook Medical, Bloomington, IN) was mounted. After passage of the AIC, I would railroad a 6.5-mm ID intubating Laryngeal Mask Airway ™ (LMA ™) endotracheal tube over it. If the AIC passed easily, I anticipate that the intubating LMA ™ endotracheal tube would also pass. If the AIC was tight/snug, I would pass a Cook airway exchange catheter through the AIC and railroad a 5.0-mm ID microlaryngoscopy tube over the airway exchange catheter. I would then confirm position of the endotracheal tube beyond the stenosis. If the AIC could not pass without undue force, I would ventilate until paralysis was reversed (sugammadex may be useful here due to its ability to produce rapid and complete reversal of rocuronium paralysis) and then wake up the patient. During surgery, I would administer 8.0 mg of intravenous dexamethasone to minimize edema of the stenotic region. At the end of surgery, I would exchange the endotracheal tube for a Cook airway exchange catheter and a PLMA ™. I would then assess ease of ventilation (and spirometry) with the patient still anesthetized. I would then allow the patient to wake and remove the PLMA ™, but not the exchange catheter. If there was any suggestion of trauma during the intubation or concern about edema at the time of extubation, I would admit the patient to intensive care unit for 24-48 h of sedation, ventilation, and steroid to allow airway edema to settle.The history of tracheal surgery and persistent stridor suggested a rigid tracheal wall at the stenotic region allowing insertion of an endotracheal tube with 5-7 mm outer diameter, that is, only 4.0-5.5 mm ID without injuring the tracheal wall. We considered that positive pressure ventilation with such a small diameter tube might be difficult in this obese patient during surgery in prone position. Furthermore, traumatic insertion and prolonged placement of a larger diameter tube were considered to be disadvantageous because of the potential for development of mucosal edema and further narrowing of the trachea after tracheal extubation. Therefore, we decided not to intubate the trachea, but to use the PLMA ™ for positive pressure ventilation. The patient agreed with this strategy after we explained its potential benefits and risks to him.Because of clinical symptoms and body habitus suggesting potential obstructive sleep apnea, we performed nocturnal oximetry preoperatively. We calculated 4% oxygen desaturation index (i.e. , the average number of oxygen desaturations by 4% or more below the baseline level per hour). Although an oxygen desaturation index greater than 5 h−1is suggestive of sleep-disordered breathing, the index was 3 h−1in this patient.11Despite the negative result of the sleep study, nasal continuous positive airway pressure was prescribed because this could help maintain tracheal patency both for treatment of his snoring and in case of mucosal edema at the tracheal stenosis developed after surgery. The patient tolerated this treatment well.General anesthesia was induced with intravenous administration of remifentanil, propofol, and vecuronium, and a PLMA ™ (#5) was inserted, guided by a gum elastic bougie. Anesthesia was maintained with inhaled sevoflurane and an infusion of intravenous remifentanil. With pressure-controlled ventilation during surgery (peak inspiratory pressure 22 cm H2O, positive end-expiratory pressure 7 cm H2O, respiratory rate 8 breaths/min, inspiratory expiratory ratio 1:3) through the PLMA ™, we saw no signs of high airway resistance or airflow limitation such as low tidal volume or lack of formation of an alveolar plateau on capnography (tidal volume 730 ml, end-tidal CO231 mmHg). The surgery was uneventfully accomplished. The PLMA ™ was removed when the patient was fully aroused. Optimal postoperative analgesia was achieved by intravenous injection of nonsteroidal antiinflammatory drug and a continuous intravenous infusion of fentanyl. After the patient arrived on the ward, nasal continuous positive airway pressure with oxygen was applied immediately and was continued for three postoperative nights. This was effective in eliminating both snoring and stridor during sleep.12He did not complain of dyspnea after surgery and was discharged fully mobile.I believe that preoperative assessment and anesthesia management of the case described are generally reasonable and accord with my assessments and plans.The preoperative respiratory state during wakefulness and sleep was sufficiently assessed, and the visual assessments of the stenotic region with three-dimensional CT imaging of the trachea in addition to chest radiographs were informative. These meticulous assessments may certainly be useful to plan a safer anesthesia management (providing that the time and cost can be spent). Nevertheless, caution may be required, because the absence of significant airway obstruction during sleep does not guarantee that there will be no airway obstruction during anesthesia. There have been several reports of complete airway obstruction in patients with mediastinal without any preoperative signs of airway this case, the three-dimensional CT and preoperative assessments that complete airway obstruction is but it might have been safer to induce anesthesia by of increasing concentrations of a anesthetic as and then to a neuromuscular blocking after that no airway obstruction has may be two major possible problems with the anesthesia management performed by Drs. and may occur beyond the stenosis, when the ventilation is This can be reduced by the ratio is increasing the expiratory In this case, because the stenosis had a the pressure-controlled ventilation and ventilation volume was breathing might have been a choice ventilation had been during possible is that the use of the PLMA ™ might have difficult not likely in this the device had been or airway obstruction at the stenotic region had If there are about to the patient's or about a prolonged operation I would use a backup method of a tube-exchange catheter beyond the stenosis and an endotracheal tube with its tip proximal to the nasal continuous positive airway to minimize airway was applied for three postoperative nights. tracheal intubation not the choice of nasal continuous positive airway pressure than my plan of a tube to the trachea after possible solution that is several potential complications I will to the following I do not my plans would Drs. and have the of their plans In most in this case is not plan A is, but the plans to plan A immediately or is for the to have a plan as a before induction of first is that of this patient's care at the of supraglottic and problems to both difficult mask ventilation and difficult will be rapid and severe the airway is in this obese patient who will have a of a tube beyond his tracheal narrowing may be the most there are two patient that I the that the tracheal narrowing only 5 mm in its minor is mm in its major diameter to that it will admit a larger endotracheal tube than with an diameter of 5 The trachea is a and and who has tracheal will confirm that it will a larger diameter tube than its the that the patient no limitation to his daily activities indicates that gas flow is than of the patient's did consider use of the PLMA ™ as the airway anesthesia. The PLMA ™ is my airway and I have with it for both difficult airway is my in it that I have use of the ™ Mask because I believe that its and safety is to that of the PLMA ™. Despite I its use for this case because I was that it with the patient in the prone position, would be and might with did not consider the of use of PLMA ™ with an airway exchange catheter in place through the vocal in case was This is and a level of Despite I was required to this patient I would still tracheal intubation before a in the prone position. I have used the PLMA ™ in approximately patients in the prone position and I that it has been used in several of patients in the prone the patients in were at low risk and the largest is airway obstruction in three patients In the patient in this case has an increased risk of problems with both ventilation and degrees of and airway during surgery in the prone position would likely to airway If airway obstruction in this would likely be rapid and airway is likely difficult to in the supine position in Despite my I would be that problems in the prone position, would be so difficult to that the patient's would be at Despite the by intubation (and I would tracheal intubation in this spontaneous breathing induction of anesthesia, for a With the of I have a for use of a dose of target-controlled propofol, while maintaining spontaneous ventilation. There are only of this of target-controlled infusion of propofol over rapid intravenous induction is that spontaneous ventilation is The also has over propofol that the of anesthesia. increasing depth of anesthesia is of the patient's ventilation. This rate of increase of the depth of anesthesia to be titrated by the than by the also that is the infusion immediately anesthesia to without the patient to anesthesia via an airway that was and has airway are so increased and the complications to during induction are In patients will ventilation when still responsive to verbal This confirmation of ability to or of increasing and airway (e.g. , are tolerated and than during the does to to problems with the airway PLMA ™ is a device with a in management of the difficult there is in PLMA ™ it is that insertion can be more difficult than for supraglottic airway insertion enable a insertion rate with the PLMA ™ of lower than that for the is that the use of a first pass with the PLMA ™, increasing to without any increase in in I consider first time to be I insert the PLMA ™ over a gum elastic the type of is to minimize the risk of AIC is the tube to use to intubate via a supraglottic airway and intubate narrow has the diameter than of any endotracheal tube that will over a size fiberscope and its ID that it does not during on the use via the and PLMA ™ in difficult airway management is in two placed it oxygenation and on placement of a larger endotracheal tube over or a an airway exchange catheter through by the small minor diameter of the trachea the significant of with ventilation or If ventilation becomes at any after induction or intubation with an AIC is not possible, my plan is before another are before any have been I would at an endotracheal tube, tracheal the of loss of the airway, with my will be ventilation using a (VBM Medizintechnik, Sulz, the a so that the may only the pressure to ventilate the the risk, and of any would be via the Ravussin cannula, placed before induction of anesthesia. and a is not an time to place a cricothyroid cases of difficult airway management which to of cases with and in of cases a surgical airway was but was placed to and ventilation performed in were with a high incidence of Although cases are by the is for and a patient before is a The of insertion of a cricothyroid cannula for difficult airway management has been is a of my management of patients with airway is performed in the awake is and is the catheter would be placed under as this position and in this case that may not be is more when the is before difficult that may I to use the cricothyroid cannula I would not anticipate with but care would be to that full had over or before the placing a on the patient's chest and complete chest is a useful to confirm complete would to severe in clinical anesthesia, there may be no or several appropriate The airway airway management strategies for this patient. this does not airway through this case scenario, of the is that we agreed that ventilation would be possible during anesthesia Despite did we airway management strategies and in plans in case of this is either because preoperative assessments of airway size and may be in ease of ventilation during general anesthesia or because the airway management and for managing tracheal stenosis is also in patients with severe tracheal stenosis, normal gas exchange is maintained by respiratory Therefore, the presence of hypercapnia in preoperative patients without respiratory indicates the potential for of both spontaneous and mechanical ventilation during general anesthesia. In the ability to breathing through a narrow airway is during general anesthesia and than that during because such as and are and oxygen is and breathing through a of mm ID and cm in or mm ID and cm in reduced the ventilation by 7 and during general anesthesia, were and The by and and confirm that the narrowing through which patients can breathe without an increase in mm for breathing through a is achieved by the respiratory with of both inspiratory and expiratory and the increase in respiratory Although the patient's respiratory or during assisted and ventilation, size of the stenosis for breathing may not be by the I that no has the stenosis for mechanical ventilation in and patients and the to be in the can we assess and severity of tracheal with mild to tracheal stenosis have clinical symptoms such as patients with severe tracheal stenosis may present without stridor and dyspnea during breathing clinical symptoms may not be for severity of tracheal imaging assess the severity of the stenosis. radiographs have clinical for the presence and the severity of an airway stenosis. CT the airway significant information the and of the airway narrowing and the the developed three-dimensional imaging such as CT and imaging can more airway and the airway a fiberoptic for the and the the and the of stenotic region of the trachea in patients who trachea surgery were to be mm in and mm, suggesting of the and of the stenotic airway by the imaging of the tracheal stenosis on breathing during general anesthesia is difficult to by the imaging size is by the pressure the airway wall and its A extrathoracic airway during and during because the pressure during and during In the airway caliber and respiratory is in the intrathoracic airway. Therefore, airflow limitation not occurs in the extrathoracic airway during and in the intrathoracic airway during airway is during forced expiratory and inspiratory particularly when of the airway caliber is In this may be useful for the site of airway and airway that the during a of forced expiratory and inspiratory were greater in 12 patients with extrathoracic airway than of normal Two patients with intrathoracic had than which increased to more than after of the mediastinal and insertion of tracheal In two patients with tracheal stenosis, both and were but did not from normal to the flow-volume loop in patient had significant in both and and a normal ratio suggesting significant airway stenosis and for of the airway wall. Nevertheless, caution is required for of the because can be by patient a direct the tracheal by the CT and in with mediastinal significant but in the supine position with the sitting position and significant in after mass complete airway obstruction after induction of anesthesia in with greater than tracheal the patient with a trachea by lower and tracheal should not have general anesthesia induced before the airway. In may be useful for tracheal and for the risk of airway after induction of anesthesia, but further are the airway is the severity of airflow limitation is by airway the a significant and the of the airway stenosis, and might be used as a useful for airway size without imaging of the of the of stenotic and airway to airway may have over imaging information as an index for upper airway that was greater than in patients with upper airway to a normal breathing through an resistance of than mm diameter (fig. through a in mechanical ventilation during general anesthesia, increased the to more than In patient with 3 cm tracheal stenosis with of is calculated as = The is than that in normal and to breathing through at to 8 mm Therefore, this assessment possible breathing or mechanical ventilation during general anesthesia, airway This assessment of the tracheal stenosis can significant information for perioperative airway management strategies (fig. 1). of more than to 4 mm may a potential of mechanical ventilation after induction of general anesthesia, this to be and should be considered in we anesthetic management of a patient with tracheal stenosis and airway management strategies of and accurate of airway patency and breathing during general anesthesia in the patient with tracheal stenosis to be the for the airway management For patients with difficult in preoperative airway assessment as a is when with the in airway management and Cook United United and United with of the case assisted in of and of the of for his with of this

Freire C, Sennes LU, Polotsky VY. Opioids and obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):647-652.

Postoperative Tracheal Extubation

Although tracheal intubation receives much attention, especially with regard to management of the difficult airway, tracheal extubation has received relatively little emphasis. The scope and significance of problems occurring after tracheal extubation are real. Adverse outcomes involving the respiratory system comprise the single largest class of injury reported in the ASA Closed Claims Study [1]. Obvious adverse events related to tracheal extubation accounted for 35 of the 522 or 7% of the respiratory-related claims. Certainly additional morbidity related to extubation could be accounted for in other categories of adverse respiratory events, such as inadequate ventilation, airway obstruction, bronchospasm, and aspiration. Others have documented a 4%-9% incidence of serious adverse respiratory events in the immediate postextubation period [2,3] and preventable anesthesia-related etiologies were noted as important by Ruth et al. [2]. Mathew et al. [4], in a retrospective review of more than 13,000 anesthetics, noted that emergency tracheal reintubations occurred in only 0.19% of patients, and that the majority of tracheal reintubations were due to preventable anesthesia-related factors. Perhaps a greater percentage of patients experience postextubation difficulties but do not require reintubation of the trachea. Reasons for tracheal reintubation in the intensive care setting may differ, but the reported incidence in that arena is similarly 4% [5]. Anesthesiologists recognize the immediate postextubation period as one where patients are particularly vulnerable. Events such as laryngospasm, aspiration, inadequate airway patency, or inadequate ventilatory drive can occur and frequently result in hypoxemia. Such hypoxemia is most often corrected within minutes. Less frequently, postextubation hypoxemia can rapidly result in serious morbidity. In this report we will review the known physiologic and pathophysiologic changes associated with anesthesia and surgery that can influence respiratory function after tracheal extubation, the physiologic impact of extubation itself, criteria used for predicting successful extubation, and different techniques and interventions used for tracheal extubation. It is not our intent to review the complications of laryngoscopy and tracheal intubation. However, common complications of tracheal intubation, with special emphasis on the airway, will be discussed in detail as they frequently affect respiratory function after tracheal extubation. More uncommon and miscellaneous complications, such as problems related to the endotracheal tube cuff, recently have been reviewed [6]. Effects of Anesthesia and Surgery on Respiratory Function After Extubation After the "ideal" extubation, patients would exhibit adequate ventilatory drive, a normal breathing pattern, a patent airway with intact protective reflexes, normal pulmonary function, and the absence of any mechanical perturbations such as coughing. Unfortunately, all of these conditions are rarely, if ever, achieved in patients extubated after anesthesia. Understanding the potential interactions between anesthesia, surgery, and extubation on respiratory function helps define many of the complications that occur at this crucial juncture in anesthesia care. This section will include a discussion of the effects of anesthesia and surgery on the respiratory system which are common during extubation, with major emphasis on the airway and lung. Airway Changes Any form of airway dysfunction, such as obstruction after tracheal extubation, is an immediate threat to patient safety. Significant airway compromise leads to diminished minute ventilatory volumes and hypoxemia ensues in a variable, but often rapid fashion. A differential diagnosis of acute postoperative obstruction of the upper airway after extubation includes: laryngospasm, relaxed airway muscles, soft tissue edema, cervical hematoma, vocal-cord paralysis, and vocal-cord dysfunction Table 1. Airway obstruction from foreign body aspiration (e.g., temperature probe condoms) will not be reviewed but deserves mention.Table 1: Differential Diagnosis of Postoperative Airway ObstructionLaryngospasm Laryngospasm, defined by Keating [7] as a protective reflex, can be life-threatening when it occurs after extubation. Historically, a patient in Stage II anesthesia has been thought to be particularly vulnerable to laryngospasm [8]. Stimulation of a variety of sites from the nasal mucosa to the diaphragm can evoke laryngospasm [9]. Most commonly, laryngospasm is a reaction to a foreign body or substance near the glottis. Blood or saliva, even in small amounts, can elicit laryngospasm. It has been suggested that laryngospasm can be prevented by extubating a patient under deep anesthesia, while the laryngeal reflexes are depressed [8]. However, substantial proof of this tenet is lacking. Suzuki and Sasaki [10] contend that laryngospasm is solely attributable to prolonged adduction of the vocal cords mediated via the superior laryngeal nerve and cricothyroid muscle. Ikari and Sasaki [11] have demonstrated that the firing threshold of the laryngeal adductor neurons involved in laryngospasm varies in a sinusoidal manner during spontaneous ventilation. Interestingly, reflex laryngeal closure occurs more readily during expiration than inspiration Figure 1. Others believe that laryngospasm also involves closure of the glottis in addition to adduction of the vocal cords. Closure of the glottis results from contraction of the lateral cricoarytenoid and thyroarytenoid muscles, which are innervated by the recurrent laryngeal nerve [9]. Clinical recognition and treatment of laryngospasm must be expedient (see below), if complications such as hypoxemia or pulmonary edema are to be avoided [12].Figure 1: Mean threshold in volts for reflex glottic closure (laryngospasm) plotted with respect to respiratory phase. Note the increased threshold during inspiration. (Adapted with permission from: Ikari T, Saski CT. Glottic closure reflex control mechanisms. Ann Otol 1980;89:220-4.)Airway Relaxation Airway obstruction related to relaxation of airway soft tissue is frequently associated with residual effects of anesthesia. Such obstruction is purported to be most commonly due to relaxation of the airway (pharyngolaryngeal) muscles. Physiologic maintenance of upper airway patency occurs by a complex mechanism that involves the muscles inserted into the hyoid bone and thyroid cartilage [13]. During normal inspiration, an increase in tonic activity of these strap muscles precedes contraction of the diaphragm and prevents apposition of the tongue and soft palate against the posterior pharyngeal wall [14]. Drummond [15], administered sodium thiopental to 14 patients which resulted in a decrease in electromyographic activity of the strap muscles that was associated with airway obstruction. Airway collapse has been prevented by stimulation of the strap muscles in rabbits [16]. The mechanisms of airway obstruction in sleep disorders also involves a decrease in the tonic activity of these upper airway muscles. The actual tissue producing obstruction is a point of debate, but likely sites include the tongue, soft palate, and/or epiglottis. Evidence implicating the tongue as responsible for upper airway obstruction after extubation is derived from several sources including descriptions of the mechanism of obstruction in unconscious patients, other sleep apnea studies, and several anesthesia reports [17-21]. Safar et al. [17], after evaluating lateral radiographs in anesthetized patients concluded that obstruction is secondary to posterior prolapse of the tongue. Sleep apnea patients also experience obstruction from relaxation of the tongue secondary to decreased airway muscle tone that occurs during rapid eye movement sleep [18,19]. Studies using electromyograms in obstructive sleep apnea patients have recorded decreased activity of the genioglossus muscle concurrent with airway obstruction [19]. Nishino et al. [20], reported decreases in hypoglossal nerve activity which correlated inversely with increasing halothane concentrations in cats; however, there were no observations concerning airway obstruction. In addition, reports of intraoperative airway obstruction during bilateral carotid endarterectomy under cervical plexus block suggest bilateral hypoglossal nerve dysfunction as a contributing factor [21]. Using fluoroscopy and lateral radiography, others have demonstrated that obstruction occurs at the level of the soft palate in sleep apnea patients [22]. Nandi et al. [23] demonstrated obstruction at the soft palate in 17 of 18 patients, the epiglottis in 4 of 18 patients, and the tongue in 0 of 18 patients Figure 2 and Figure 3. Boiden [24], using bronchoscopy, had similar findings, and proposed that the relative position of the hyoid bone to the thyroid cartilage determines the degree of airway patency [24]. Thus, the head tilt and jaw thrust recommended by Morikawa et al. [25] results in ventral movement of the hyoid bone relative to the thyroid cartilage, and is effective in opening the airway. The soft palate appears to be the most likely site of airway obstruction. Nevertheless, prolapse of the tongue, especially when it is large, can probably also impair airway patency.Figure 2: Radiographic evidence before (left) and after (right) induction of anesthesia, demonstrating soft palate obstruction of the airway during anesthesia. Arrows indicate airway opening and narrowing. (Adapted with permission from Nandi PR. Effect of general anaesthesia on the pharynx. Br J Anaesth 1991;66:157-62.)Figure 3: Diagrammatic representation of the pharyngeal outline based on radiograph Figure 2 measurements before (solid line) and after (dotted line) induction of anesthesia. 1, soft palate; 2, base of tongue; 3, hyoid bone; 4, epiglottis. (Adapted with permission from Nunn JF. Effect of general anaesthesia on the pharynx. Br J Anaesth 1991;66:157-62.)Pharyngolaryngeal Edema Uvular and/or soft palate edema is a potential cause of postextubation airway obstruction [26]. The pathophysiology of uvular edema is undetermined, but suggested possibilities include mechanical trauma and/or impeded venous drainage from airway devices including endotracheal tubes [27], oral airways [28], nasal airways [29], laryngeal mask airways [30], and vigorous suctioning of the airway [31]. Pregnant patients, and especially those with toxemia, may experience significant uvular and/or pharyngolaryngeal edema and related airway obstruction [32]. Surgery involving the anterior neck, including dissections or cervical spine operations, may also result in pharyngolaryngeal edema and airway obstruction. Avoiding bilateral neck dissections in an attempt to prevent serious edema has been recommended [33], but, significant edema and supraglottic obstruction can occur even after delayed contralateral second stage procedures [34]. One proposed mechanism of edema after neck surgery is the physical disruption of lymphatic drainage. Emery et al. [35] presented a review of seven cases of postoperative upper airway obstruction after anterior cervical spine surgery. Five of the seven patients had evidence of pharyngolaryngeal edema, while none of the seven cases had evidence of cervical hematoma. Cervical Hematoma Cervical hematoma after anterior neck surgery can also cause airway obstruction. Such hematomas can develop postoperatively, and cause delayed airway obstruction after extubation. The purported mechanism of airway obstruction associated with cervical hematoma is the obstruction of venous and lymphatic systems by the expanding mass, resulting in pharyngolaryngeal edema [36]. Edematous mucosal folds can eventually obliterate the glottis [36]. Compression of adjacent airway structures, such as the trachea, by a hematoma is not commonly found [37]. O'Sullivan et al. [36], described the postoperative course of six carotid endarterectomy patients who formed cervical hematomas. Stridor and respiratory compromise, which required immediate surgical intervention, developed in four of six patients. After induction of general anesthesia, three of these patients were impossible to manually ventilate and two could not be intubated. The two patients without evidence of stridor also returned to the operating room. One of these two could not be manually ventilated and both were difficult to intubate. Another reported case of cervical hematoma involved a 57-yr-old patient who developed airway obstruction 12 h after thyroidectomy. A significant hematoma developed, but its evacuation did not relieve airway obstruction. The persistent airway obstruction was thought to be secondary to pharyngolaryngeal edema [38]. The incidence of cervical wound hematoma after carotid endarterectomy is cited as 1.9%, with an unknown percentage of these patients developing airway obstruction [39]. When these patients return to the operating room for reexploration, the absence of stridor or respiratory distress does not predict freedom from "difficult airway" problems. Hematoma, as well as pharyngolaryngeal edema, may render manual ventilation by mask and/or visualization of the vocal cords and tracheal intubation difficult or impossible. In addition, evacuation of the hematoma may not ameliorate existing airway compromise. Such patients should be extubated cautiously and when there is evidence that pharyngolaryngeal edema has diminished. Lingual Edema Oral surgery can produce edema of the tongue and compromise postoperative airway function, especially after palatoplasty or pharyngeal flap surgery [40]. Prolonged placement of a mouth gag, commonly used in cleft palate repair, can result in lingual edema as described by Schettler [41]. Periodic relief of pressure from mouth gag devices should help reduce associated lingual edema [42]. Head position during neurosurgery has also been reported to contribute to lingual edema. Patients undergoing a craniotomy in the sitting position may have their head in such extreme flexion that obstruction of venous drainage of the tongue results in lingual edema, macroglossia, and airway obstruction [43]. During such head flexion the presence of an oral airway may exacerbate compression of the tongue and further compromise lingual circulation. An allergic reaction to glutaraldehyde solution, used to sterilize laryngoscope blades, is another unique cause of lingual edema. Edema can be so severe as to lead to reintubation during recovery [44]. Severe allergic reactions in general may involve part or all of several airway structures and can also result in edema and airway compromise. Vocal Cord Paralysis Unilateral vocal cord paralysis may cause persistent hoarseness after extubation [45]. Bilateral vocal cord paralysis may produce upper airway obstruction [46,47]. Vocal cord paralysis is usually secondary to injury of the recurrent laryngeal nerve resulting in unopposed superior laryngeal nerve mediated adduction of the vocal cords. Such an injury can occur with neck surgery (especially thyroidectomy) [48], thoracic surgery [49,50], internal jugular line placement [51], and endotracheal intubation [52-55]. Endotracheal tubes are frequently cited as a cause of vocal cord paralysis, and suggested mechanisms include endotracheal tube cuff compression of the recurrent laryngeal nerve against the lamina of the thyroid cartilage. Positioning of the endotracheal tube cuff just below or adjacent to the vocal cords may increase the incidence of this problem. Excessive cuff inflation and/or high cuff pressures resulting from diffusion of nitrous oxide can also contribute to vocal cord damage, especially in cuffs that are positioned just below the cords. Vocal Cord Dysfunction Vocal cord dysfunction (VCD) is an uncommon clinical cause of airway obstruction. VCD was first described in 1902 by Osler [56]. It has since been described by various synonyms, including paroxysmal vocal cord motion [57], factitious asthma [58], emotional laryngeal wheezing [59], and Munchausen's stridor [60]. All of the above entities are similar in their clinical presentation. The patient population, from the few reported cases [61,62], appears to consist predominantly of young females with a recent history of an upper respiratory tract infection and emotional stress [59,61,63]. VCD presents with laryngeal stridor or upper airway wheezing similar to asthma [59,64], but the wheezing is unresponsive to bronchodilator therapy [58,63,65]. Patients complain of inspiratory difficulties that result from paradoxical adduction of the vocal cords during inspiration [59]. Obstruction can be severe and require the institution of an artificial or surgical airway [61,66]. Flow volume loops will reveal variable extrathoracic obstruction with a marked decrease in inspiratory flow compared to expiratory flow [61], but visualization of the vocal cords during a symptomatic episode is necessary for a definitive diagnosis [67]. Recommendations for successful extubation of these patients include avoiding an awake extubation or, if possible, providing adequate sedation at the time of extubation. Sedation alleviates the dynamic inspiratory obstruction by reducing inspiratory effort and flow. Treatment of a VCD episode includes verbal reassurance, asking the patient to focus on the expiratory phase of breathing [62], and sedation if the diagnosis of VCD as the cause of respiratory distress is certain [58]. Laryngeal Incompetence Several investigations have demonstrated that laryngeal incompetence occurs after extubation whether or not residual anesthetic effects are present. Tomlin et al. [68] evaluated 56 patients undergoing simple surface surgery under "light" balanced anesthesia; 12 patients developed postoperative atelectasis, 6 of whom aspirated when asked to swallow 10 mL of contrast medium 2 or more hours after surgery. The majority of these patients (4 of 6) demonstrating this finding had been intubated. Gardner [69] demonstrated aspiration in 10 of 94 patients 2 to 4 days after extubation, and Siedlecki et al. [70] found that 27% of responsive patients aspirated radiopaque dye immediately after extubation. Cardiac surgery patients also have a high risk (33%) of aspiration when extubated early (less than 8 h) after surgery, even if awake. This risk significantly decreases to 5% when extubation is performed later [71]. Residual anesthetic effects may contribute to this high incidence of aspiration in the early postoperative period. In summary, laryngeal incompetence is common and the risk of aspiration after extubation is not eliminated by the presence of consciousness. Swallowing Swallowing, another airway protection reflex, can also be impaired by a host of factors after surgery and anesthesia. As recently reviewed [72], topical anesthetics, tracheostomy, tracheal intubation, neurologic or airway structure injury, conscious intravenous sedation, inhalation of 50% nitrous oxide, and even sleep can depress swallowing and permit pulmonary aspiration. Pavlin et al. [73] and Isono et al. [74] have also demonstrated that partial paralysis with neuromuscular blockers depresses swallowing, too. Control of Breathing While it is not the purpose of this review to completely describe the impact of anesthesia on the control of breathing, it is necessary to highlight the major factors affecting ventilatory drive during tracheal extubation. Airway function is also linked to the central neural control of breathing and, like spontaneous ventilation, is depressed by anesthesia. Inhalation drugs, opioids, sedative-hypnotics, and muscle relaxants are the common anesthetics that can depress the ventilatory response to carbon dioxide and/or hypoxia. Significant residual drug effects are often present at the time of tracheal extubation. Inhalation drugs alter the regulation of CO2 partial pressures, as evidenced by the correlation between increasing alveolar concentrations of various potent inhaled anesthetics, and increases in resting CO2 tensions and declines in ventilatory responses to CO2[75-77]. Low concentrations of the potent inhalation drugs (less than 0.5 minimum alveolar anesthetic concentration (MAC)) should not, in and of themselves, produce clinically troublesome blunting of ventilatory response to CO2 during extubation and recovery from surgery [78]. However, low concentrations of potent inhalation drugs may blunt the hypoxic ventilatory response and such an effect can pose a significant risk. Halothane, enflurane, and isoflurane, at 1 MAC in dogs, produce significant depression of hypoxic ventilatory drive. Enflurane has been reported to be the greatest depressant of hypoxic ventilatory drive and isoflurane the least [79]. Knill et al. [78,80,81] performed several investigations of hypoxic ventilatory drives in humans and demonstrated that even low concentrations (0.1 MAC) of halothane and enflurane greatly decrease the ventilatory response to isocapnic hypoxia. A more recent report suggests that hypoxic ventilatory drive may not be depressed by low concentrations of isoflurane [82]. Decreases in hypoxic, but not hypercapnic, ventilatory drive occur with nitrous oxide as well [83]. All mu receptor opioid including and produce depression of ventilation, a on the respiratory The of the respiratory to CO2 is significantly by The of the ventilatory response to CO2 is and minute ventilatory responses to increases in are to the The threshold and resting are also increased by Thus, the mechanism the body minute ventilation and from significant increases in CO2 and respiratory is significantly impaired by also decrease hypoxic ventilatory drive and blunt the increase in respiratory drive associated with increased such as increased airway or recurrent respiratory depression can occur in patients from general anesthesia who have received and for this include a of stimulation or of and other after activity of in and have noted second in during the phase in produce decreases in CO2 and breathing have also been to decrease the acute ventilatory response to and This is not as as that after opioid of significant residual effects with can be by of the of of the and can also decrease hypoxic ventilatory drive, by in the carotid body is one of the carotid body involved in hypoxic ventilatory drive of troublesome ventilatory depression can occur after extubation without extubation, patient and recovery room can result in significant patient these events have stimulation can and result in an with inadequate and/or ventilation. especially in with the of opioid results in significant depression of ventilatory drive Function The significant physiologic and, at pathophysiologic changes during general anesthesia that can after tracheal extubation. changes frequently include decreased in of breathing, and depressed changes are rarely, if ever, of can be and, at may result in significant patient morbidity. Thus, the impact of anesthesia and surgery on function can significantly influence results after tracheal extubation. The most and volume after extubation is an increase in which occurs as a result of the endotracheal tube volume with the upper airway Significant changes in residual also occur usually decreases by of or mL with induction of general anesthesia Postoperative decreases in are associated with surgery of the or It is whether is decreased immediately after tracheal extubation. et al. and and demonstrated is not decreased immediately after extubation, it is decreased several hours et al. demonstrated a decrease in in of patients 1 h after surgery. The decrease in after induction of anesthesia and after extubation may be by different mechanisms The decrease in immediately after induction was well by et al. In that of compression Figure The mechanism for this decrease in after induction of anesthesia has been to a of the diaphragm and increased volume Interestingly, neuromuscular block after induction of general anesthesia does not result in a further decrease in The mechanism postoperative decreases in is usually related to dysfunction et al. reported that dysfunction after surgery could to 1 and resulted in a greater on movement for dysfunction is to be secondary to surgical inadequate and/or In addition to dysfunction, another cause of postoperative decreases in is breathing of can and and of the before and after induction of anesthesia, demonstrating of compression in the of both (Adapted with permission from et al. during anesthesia with of the clinical of decreases in are often not decreases in are often to cause Figure 4 and that impair and decrease Such volume if present at the time of extubation, can compromise a to airway difficulties by the time for and of hypoxemia. The incidence of most frequently defined as an than after extubation and recovery from general anesthesia is As many as of and of after a general anesthetic will be at a care if no is during and in a review of hypoxemia during and after anesthesia, postoperative into early and inadequate minute ventilation or airway obstruction, other of early hypoxemia include increased increased diffusion of hypoxic pulmonary and a decrease in include increased pulmonary hypoxemia more frequently than and Although the intraoperative of has been reported to increase postoperative hypoxemia the majority of have not demonstrated that the of in anesthesia is associated with an increased incidence of postoperative hypoxemia another cause of hypoxemia in patients from anesthesia was first reported by who thought the diffusion of could alveolar the of during and recovery from anesthesia the incidence of clinically significant diffusion is but not of dysfunction associated with anesthesia and surgery can also contribute to postoperative hypoxemia. from the respiratory tract Patients with have been to have delayed tracheal intubation and surgery result in dysfunction and or flow. in can contribute to impaired of Breathing extubation of a breathing patient can

Mild excerice in 7 patients with upper airway obstruction but without diffuse lung disease caused a mean decrease in arterial oxygen tension of 11 mm Hg. Exercise hypoxemia disappeared after surgical removal of obstruction in 3 patients tested. Exercise hypoxemia due to relative alveolar hypoventilation was observed in 4 normal subjects with external combined inspiratory and expiratory resistance. Analysis of mechanics of air flow through an orifice suggests that exertional dyspnea is caused by manifold increase of airway resistance during exercise; acute respiratory failure might be precipitated by further minimal reduction in airway lumen once it has reached a diameter of 8 mm. Clinicians should be alert to the possibility of upper airway obstruction in any symptomatic patient who has had tracheal intubation or in patients with obscure wheezing, especially on exercise.

The pattern of stimulated breathing during carbon dioxide inhalation was studied in a group of 21 patients with severe irreversible airways obstruction (mean FEV1 = 0.9 litre, mean FEV1/FVC% = 50%). Carbon dioxide rebreathing experiments were performed, the ventilatory response being defined in terms of total ventilation (V) and CO2 sensitivity (S). Breathing pattern was defined by the changes in tidal volume (delta VT) and respiratory frequency (delta f) and the maximum VT achieved (VTmax). Contrary to some previous studied no significant relationship could be demonstrated between the severity of airway obstruction (FEV1/FVC%, Raw) and the ventilatory response to rebreathing (V, S, delta VT, delta f, VTmax). However, measurements of dynamic lung volume (FEV1, FVC, IC) were found to be significantly correlated with the breathing pattern variables (delta VT, delta f, VTmax). Resting PaO2 and PaCO2 were significantly correlated with delta VT but not delta f. Results indicate that the degree of airway obstruction does not dictate the ventilatory or breathing pattern response to carbon dioxide induced hyperpnoea. In contrast it is the restriction of dynamic lung volume, by limiting the VT response, that appears to determine the ventilatory and breathing pattern response in patients with severe airway obstruction.

Upon ascent to high altitude, cerebral blood flow (CBF) rises substantially before returning to sea-level values. The underlying mechanisms for these changes are unclear. We examined three hypotheses: (1) the balance of arterial blood gases upon arrival at and across 2 weeks of living at 5050 m will closely relate to changes in CBF; (2) CBF reactivity to steady-state changes in CO2 will be reduced following this 2 week acclimatisation period, and (3) reductions in CBF reactivity to CO2 will be reflected in an augmented ventilatory sensitivity to CO2. We measured arterial blood gases, middle cerebral artery blood flow velocity (MCAv, index of CBF) and ventilation () at rest and during steady-state hyperoxic hypercapnia (7% CO2) and voluntary hyperventilation (hypocapnia) at sea level and then again following 2–4, 7–9 and 12–15 days of living at 5050 m. Upon arrival at high altitude, resting MCAv was elevated (up 31 ± 31%; P < 0.01; vs. sea level), but returned to sea-level values within 7–9 days. Elevations in MCAv were strongly correlated (R2= 0.40) with the change in ratio (i.e. the collective tendency of arterial blood gases to cause CBF vasodilatation or constriction). Upon initial arrival and after 2 weeks at high altitude, cerebrovascular reactivity to hypercapnia was reduced (P < 0.05), whereas hypocapnic reactivity was enhanced (P < 0.05 vs. sea level). Ventilatory response to hypercapnia was elevated at days 2–4 (P < 0.05 vs. sea level, 4.01 ± 2.98 vs. 2.09 ± 1.32 l min−1 mmHg−1). These findings indicate that: (1) the balance of arterial blood gases accounts for a large part of the observed variability (∼40%) leading to changes in CBF at high altitude; (2) cerebrovascular reactivity to hypercapnia and hypocapnia is differentially affected by high-altitude exposure and remains distorted during partial acclimatisation, and (3) alterations in cerebrovascular reactivity to CO2 may also affect ventilatory sensitivity.

To determine how the presence of generalised airflow limitation due to chronic obstructive lung disease affects the recognition of simulated upper airway obstruction, a study was carried out in 12 patients (mean (SD) age 57 (7) years) with chronic obstructive lung disease (FEV1% predicted 53 (22), range 21-70) and 12 matched control subjects. Patients and control subjects performed maximal inspiratory and expiratory flow-volume curves in a variable volume plethysmograph with and without upper airway obstruction simulated at the mouth with a series of polythene washers of internal diameter 4, 6, 8, 10, and 12 mm. In patients, as in normal subjects, peak expiratory flow (PEF) and maximum inspiratory flow at 50% of vital capacity (Vmax50) were more sensitive to upper airway obstruction than were FEV1 or maximum expiratory flow at 50% VC (VEmax50); but the reductions in all indices caused by simulated upper airway obstruction were smaller in the patients than in the controls. The fall in PEF (whether expressed in absolute units or as a percentages) consequent on severe (4 mm) upper airway obstruction became smaller with increasing severity of chronic obstructive lung disease. The subjects also produced flow-volume curves with and without 6 mm upper airway obstruction while breathing helium and oxygen (heliox). In both groups the effects of heliox on PEF and Vmax50 were increased when upper airway obstruction was simulated. It was confirmed that the functional recognition of upper airway obstruction is more difficult in patients with chronic obstructive lung disease than in normal subjects and this difficulty increases with severity of disease; an unusually large increase in PEF or Vmax50 while the patient is breathing heliox should raise the suspicion of coexisting upper airway obstruction, but such a pattern is not specific.

The purposes of this study were to determine (1) whether an exercise stimulus could be repeatedly applied to a group of asthmatics and normal control subjects with reproducible metabolic and ventilatory consequences; (2) the effect of this stimulus on multiple aspects of pulmonary mechanics in both groups; (3) the degree of within- and between-day variation in response and the factors influencing it; and (4) the effects of pretreatment with disodium cromoglycate. Airway resistance, specific conductance, total lung capacity and its subdivisions, and forced expiratory volumes and flow rates were measured in 21 asthmatics and 8 normal control subjects before and after treadmill exercise. Minutes ventilation, tidal volume, repiratory frequency, oxygen consumption, carbon dioxide production, heart rate, and end-tidal carbon dioxide tensions were measured during exercise and recovery. The asthmatics were studied twice datly on 2 separate days. Disodium cromoglycate was administered to the asthmatics before the fourth trial. The control subjects were studied twice on the same day without any interventions. There was no difference between exercise trials as measured by any of the gas exchange variables and there were no within-day differences in baseline pulmonary mechanics in either group. In contrast to the control group, all of the asthmatics had increasing airway obstruction after the exercise challenge. There were no between -day differences in the baseline data or response to exercise in the asthmatics except that the mechanical response was less after disodium cromoglycate, which suggests that mediator release played a part. Although as a group the stimulus and response were reproducible, when data of each trial were related to the type and degree of baseline dysfunction there was a direct relationship between pre-existing obstruction and magnitude of response. This suggests that exercise-induced asthma is not an all-or-none event, but rather a continuum of responses profoundly influenced by the pre-challenge state of the airways.

In chronic obstructive pulmonary disease (COPD), the neuromuscular response to an acute increase in airflow produced by external flow resistive loads (FRL) is impaired. The present study compared the response to FRL of 15 subjects with airway obstruction due to asthma and that of 15 normal subjects. FRL were applied during progressive hypercapnia and isocapnic hypoxia produced by rebreathing techniques to permit the response to be assessed at the same degree of CO2 or O2 drive. The neuromuscular response to FRL was assessed from the airway occlusion pressure developed 100 msec after the onset of inspiration (P100), as well as ventilation. During control rebreathing, ventilatory responses to hypercapnia (ratio of change in minute ventilation to change in PCO2, delta VE/delta PCO2) and hypoxia (ratio of change in VE to the change in percentage of O2 saturation, delta VE/deltaSO2) were the same in asthmatic and normal subjects despite differences in the mechanics of breathing. The P100 response to hypercapnia delta P100/delta PCO2) and hypoxia (delta P100/delta SO2) as well as absolute P100 at any given degree of O2 and CO2 drive was greater during control rebreathing in asthmatics than in normal subjects (P less than 0.05). FRL values of 9 and 18 cm H2O per L per sec applied during either hypercapnia or hypoxia increased the occlusion pressure to a greater extent in asthmatics than in normal subjects. Methacholine-induced bronchoconstriction was used to test the effect of acute airway obstruction on the response to FRL. Bronchoconstriction was associated with an increase in the P100 response to hypercapnia and to FRL, despite increases in lung volume and decreases in inspiratory muscle force. We conclude that: (1) asthmatics with airway dysfunction have an increased nonchemical drive to breathe mediated at least in part by sensory receptors in the airways; (2) asthmatics with airway obstruction respond supernormally to acute changes in resistance to airflow, unlike subjects with COPD. The failure of COPD subjects with prolonged airway obstruction to respond to FRL may be due to adaptation of the sensory mechanisms that respond to changes in airway resistance.

We evaluated the ability of air and helium-O2 maximal expiratory flow-volume curves to distinguish upper airway obstruction from the diffuse, peripheral airway obstruction of chronic obstructive pulmonary disease. The increase in expiratory flows at peak, 75, 50, and 25 per cent of the vital capacity during helium-O2 breathing compared to air breathing was determined in 5 normal subjects and 3 patients with chronic obstructive pulmonary disease while breathing through fixed resistances, and in 6 patients with documented tracheal obstruction. In the normal subjects, the helium response at all 4 points remained normal and was unchanged from baseline until the simulated obstruction was severe (6-mm orifice), at which point all ofthe helium responses increased by 50 per cent. The patients with chronic obstructive pulmonary disease maintained their low baseline helium responses until the obstruction was severe (6-mm orifice), when only the expiratory flows at peak, 75, and 50 per cent of the vital capacity increased by at least 50 per cent. Five of the 6 patients with upper airway obstruction had helium responses very similar to those of the normal subjects with similar degrees of simulated obstruction, but the one patient with concomitant airway obstruction extending well below the carina had very small helium responses at each point. We conclude that upper airway obstruction can usually be identified by high helium responses and that upper airway obstruction, if severe, can be identified even in the presence of more peripheral airway obstruction by a normal helium response at high lung volumes.

Is Snoring a Risk Factor?

The ability to detect added external inspiratory and expiratory resistive loads was studied in normal and asthmatic subjects using sensory decision theory as a psychophysical method. Performances P(A)/delta R [where P(A) represents the index of sensitivity and delta R the additional resistor] were similar in normal and asthmatic subjects, but when sensitivity was expressed in relation to airway resistance [P(A)/delta R/Raw], asthmatics showed higher inspiratory and expiratory performances than normal subjects. After bronchodilation the relative sensitivity in the asthmatic group was impaired and approached that of normal subjects. Comparing inspiratory and expiratory load detection, normal subjects showed a higher sensitivity for expiratory than for inspiratory loads. In contrast, there was no difference in the asthmatic group. The response bias remained the same across conditions. If one accepts the assumption that the variability of sensitivity presented by asthmatic and normal subjects might be related to the variable state of their pulmonary function, our results can be interpreted as demonstrating a relationship between sensitivity and pulmonary distension or airway obstruction. These results are in agreement with the hypothesis that the site of perception for respiratory load detection is the chest wall.