Mechanical ventilation

Nasotracheal intubation

In medicine, mechanical ventilation is a method to mechanically assist or replace spontaneous breathing.

This may involve a machine called a ventilator or the breathing may be assisted by a physician or other suitable person compressing a bag or set of bellows. Traditionally divided into negative-pressure ventilation, where air is essentially sucked into the lungs, or positive pressure ventilation, where air (or another gas mix) is pushed into the trachea.

It can be used as a short term measure, for example during an operation or critical illness (often in the setting of an intensive care unit). It may be used at home or in a nursing or rehabilitation institution if patients have chronic illnesses that require long-term ventilatory assistance.

Owing to the anatomy of the human pharynx, larynx, and esophagus and the circumstances for which ventilation is required then additional measures are often required to "secure" the airway during positive pressure ventilation to allow unimpeded passage of air into the trachea and avoid air passing into the esophagus and stomach. Commonly this is by insertion of a tube into the trachea which provides a clear route for the air. This can be either an endotracheal tube, inserted through the natural openings of mouth or nose or a tracheostomy inserted through an artificial opening in the neck. In other circumstances simple airway maneuvres, an oropharyngeal airway or laryngeal mask airway may be employed. If the patient is able to protect their own airway such as in non-invasive ventilation or negative-pressure ventilation then no airway adjunct may be needed.

Mechanical ventilation is often a life-saving intervention, but carries many potential complications including pneumothorax, airway injury, alveolar damage, and ventilator-associated pneumonia..

In many healthcare systems prolonged ventilation as part of intensive care is a limited resource (in that there are only so many patients that can receive care at any given moment). It is used to support a single failing organ system (the lungs) and cannot reverse any underlying disease process (such as terminal cancer). For this reason there can be (occasionally difficult) decisions to be made about whether it is suitable to commence someone on mechanical ventilation. Equally many ethical issues surround the decision to discontinue mechanical ventilation.

Contents

History

The Roman physician Galen may have been the first to describe mechanical ventilation: "If you take a dead animal and blow air through its larynx [through a reed], you will fill its bronchi and watch its lungs attain the greatest distention."[1] Vesalius too describes ventilation by inserting a reed or cane into the trachea of animals[2]. In 1908 George Poe demonstrated his mechanical respirator by asphyxiating dogs and seemingly bringing them back to life.[3]

Negative pressure machines

An Iron Lung

The iron lung, also known as the Drinker and Shaw tank, was developed in 1929 and was one of the first negative-pressure machines used for long-term ventilation. It was refined and used in the 20th century largely as a result of the polio epidemic that struck the world in the 1940s. The machine is effectively a large elongated tank, which encases the patient up to the neck. The neck is sealed with a rubber gasket so that the patient's face (and airway) are exposed to the room air.

While the exchange of oxygen and carbon dioxide between the bloodstream and the pulmonary airspace works by diffusion and requires no external work, air must be moved into and out of the lungs to make it available to the gas exchange process. In spontaneous breathing, a negative pressure is created in the pleural cavity by the muscles of respiration, and the resulting gradient between the atmospheric pressure and the pressure inside the thorax generates a flow of air.

In the iron lung by means of a pump, the air is withdrawn mechanically to produce a vacuum inside the tank, thus creating negative pressure. This negative pressure leads to expansion of the chest, which causes a decrease in intrapulmonary pressure, and increases flow of ambient air into the lungs. As the vacuum is released, the pressure inside the tank equalizes to that of the ambient pressure, and the elastic coil of the chest and lungs leads to passive exhalation. However, when the vacuum is created, the abdomen also expands along with the lung, cutting off venous flow back to the heart, leading to pooling of venous blood in the lower extremities. There are large portholes for nurse or home assistant access. The patients can talk and eat normally, and can see the world through a well-placed series of mirrors. Some could remain in these iron lungs for years at a time quite successfully.

Today, negative pressure mechanical ventilators are still in use, notably with the Polio Wing Hospitals in England such as St. Thomas' (by Westminster in London) and the John Radcliffe in Oxford. The prominent device used is a smaller device known as the cuirass. The cuirass is a shell-like unit, creating negative pressure only to the chest using a combination of a fitting shell and a soft bladder. Its main use is in patients with neuromuscular disorders who have some residual muscular function. However, it was prone to falling off and caused severe chafing and skin damage and was not used as a long term device. In recent years this device has re-surfaced as a modern polycarbonate shell with multiple seals and a high pressure oscillation pump in order to carry out biphasic cuirass ventilation.

Positive pressure machines

Mechanical ventilator

The design of the modern positive-pressure ventilators were mainly based on technical developments by the military during World War II to supply oxygen to fighter pilots in high altitude. Such ventilators replaced the iron lungs as safe endotracheal tubes with high volume/low pressure cuffs were developed. The popularity of positive-pressure ventilators rose during the polio epidemic in the 1950s in Scandinavia and the United States and was the beginning of modern ventilation therapy. Positive pressure through manual supply of 50% oxygen through a tracheostomy tube led to a reduced mortality rate among patients with polio and respiratory paralysis. However, because of the sheer amount of man-power required for such manual intervention, mechanical positive-pressure ventilators became increasingly popular.

Positive-pressure ventilators work by increasing the patient's airway pressure through an endotracheal or tracheostomy tube. The positive pressure allows air to flow into the airway until the ventilator breath is terminated. Subsequently, the airway pressure drops to zero, and the elastic recoil of the chest wall and lungs push the tidal volume -- the breath—out through passive exhalation.

This is an example of a neonatal (infant) ventilator.

Indications for use

Mechanical ventilation is indicated when the patient's spontaneous ventilation is inadequate to maintain life. It is also indicated as prophylaxis for imminent collapse of other physiologic functions, or ineffective gas exchange in the lungs. Because mechanical ventilation only serves to provide assistance for breathing and does not cure a disease, the patient's underlying condition should be correctable and should resolve over time. In addition, other factors must be taken into consideration because mechanical ventilation is not without its complications (see below)

Common medical indications for use include:

Types of ventilators

Ventilation can be delivered via:

Modes of ventilation

Conventional ventilation

The modes of ventilation can be thought of as classifications based on how to control the ventilator breath. Traditionally ventilators were classified based on how they determined when to stop giving a breath. The three traditional categories of ventilators are listed below. As microprocessor technology is incorporated into ventilator design, the distinction among these types has become less clear as ventilators may use combinations of all of these modes as well as flow-sensing, which controls the ventilator breath based on the flow-rate of gas versus a specific volume, pressure, or time.

Breath termination

Modes of ventilation are classified by the means that they determine the inspired breath is complete. This is sensed by either pressure or volume.

Several manufactures have incorporated features from both of theses modes in an attempt to accommodate patients needs.
These modes are flow-variable, volume-targeted, pressure-regulated, time-limited modes (for example, pressure regulated volume control - PRVC). This means that instead of providing an exact tidal volume each breath, a target volume is set and the ventilator will vary the inspiratory flow at each breath to achieve the target volume at the lowest possible peak pressure. The inspiratory time (Ti) limits the length of the inspiratory cycle and therefore the I:E ratio. Pressure regulated modes such as PRVC or Auto-flow (Draeger) can most easily be thought of as turning a volume mode into a pressure mode with the added benefit of maintaining more control over tidal volume than with strictly pressure-control.

Breath initiation

The other method of classifying mechanical ventilation is based on how to determine when to start giving a breath. Similar to the termination classification noted above, microprocessor control has resulted in a myriad of hybrid modes that combine features of the traditional classifications. Note that most of the timing initiation classifications below can be combined with any of the termination classifications listed above.

APRV (Airway Pressure Release Ventilation)

APRV begins from an elevated baseline (called Phigh or measured high pressure) and achieves tidal ventilation with a brief release of the Phigh. This brief release allows CO2 removal through passive exhalation secondary to elastic recoil. The exhalation time (Tlow) is shortened to usually less than one second to prevent alveolar derecruitment and collapse - it is essentially CPAP with a brief release.

Ever increasing empirical evidence and clinical experience is showing that APRV is the primary mode of choice when ventilating a patient with ARDS or ALI (Acute Lung Injury).

Advantages to APRV ventilation include: decreased airway pressures, decreased minute ventilation, decreased dead-space ventilation, promotion of spontaneous breathing, almost 24 hour a day alveolar recruitment, decreased use of sedation, near elimination of neuromuscular blockade, optimized arterial blood gas results, mechanical restoration of FRC (functional residual capacity), a positive effect on cardiac output (due to the negative inflection from the elevated baseline with each spontaneous breath), increased organ and tissue perfusion, potential for increased urine output due to increased renal perfusion.

A patient with ARDS on average spends 8 to 11 days on a mechanical ventilator; APRV may reduce this time significantly and therefore reduce the incidence of VAP (ventilator acquired pneumonia), a risk that increases with each hour an intubated patient spends on the ventilator (VAP rate is 100% at 100 days on the vent) and carries with it a near 50% mortality rate. So, hospitals that are reporting a 0% incidence of VAP, may be improperly coding or improperly reporting.

* A controlled clinical trial testing APRV against the current ARDSNet protocol must be initiated.

High Frequency Ventilation (HFV)

Sensormedics 3100 High Frequency ventilator

High-Frequency Ventilation refers to ventilation that occurs at rates significantly above that found in natural breathing (as high as 240-900 "breaths" per minute). Within the category of high-frequency ventilation, the three principal types are high-frequency jet ventilation (HFJV), high-frequency flow interruption (HFFI), and high-frequency oscillatory ventilation (HFOV).

High Frequency Jet Ventilation employs a endotracheal tube adaptor in place for the normal 15 mm ET tube adaptor. A high pressure ‘’jet’’ of gas flows out of the adaptor and into the airway. This jet of gas occurs for a very brief duration, about 0.02 seconds, and at high frequency: 4-11 hertz. Tidal volumes ≤ 1 ml/Kg are used during HFJV. This combination of small tidal volumes delivered for very short periods of time create the lowest possible distal airway and alveolar pressures produced by a mechanical ventilator. Exhalation is passive. Jet ventilators utilize various I:E ratios--between 1:1.1 and 1:12-- to help achieve optimal exhalation. Conventional mechanical breaths are sometimes used to aid in reinflating the lung. Optimal PEEP is used to maintain alveolar inflation and promote ventilation-to-perfusion matching. Jet ventilation has been shown to reduce ventilator induced lung injury by as much as 20%.

"HFFI" operates similarly to a conventional ventilator, providing increased circuit pressure during the inspiratory phase and dropping back to PEEP during the expiratory phase.

In "HFOV" the pressure wave is driven by an electromagnetically controlled diaphragm similar to a loudspeaker. Because this can rapidly change the volume in the circuit, HFOV can produce a pressure that is lower than ambient pressure during the expiratory phase. This is sometimes called "active" expiration. In both types of high-frequency ventilation the pressure wave that is generated at the ventilator is markedly attenuated by passage down the endotracheal tube and the major conducting airways. This helps protect the alveoli from volutrauma that occurs with traditional positive pressure ventilation. Although the alveoli are kept at a relatively constant volume, similar to CPAP, other mechanisms of gas exchange allow ventilation (the removal of CO2) to occur without tidal volume exchange. Ventilation in HFO[[File:]]V is a function of frequency, amplitude, and I:E ratio and is best described graphically as the area under the curve of an oscillatory cycle. Amplitude is analogous to tidal volume in conventional ventilation; larger amplitudes remove more CO2. Seemingly paradoxical, lower frequencies remove more CO2 in HFOV whereas in conventional ventilation the opposite is true. As frequency decreases, there is less attenuation of the pressure wave transmitted to the alveoli. This results in increased mixing of gas and thus ventilation. I-time is set as a percentage of total time (usually 33%). Amplitude is a function of power and is subject to variability due to changes in compliance or resistance. Therefore, power requirements may vary significantly during treatment and from patient to patient. Patient characteristics and ventilator settings determine whether PaCO2 changes may be more sensitive to amplitude or frequency manipulation. In HFOV, mean airway pressure (MAP) is delivered via a continuous flow through the patient circuit which passes through a variable restriction valve (mushroom valve) on the expiratory limb. Increasing the flow through the circuit and/or increasing the pressure in the mushroom valve increases MAP. The MAP in HFOV functions similarly to PEEP in conventional ventilation in that it provides the pressure for alveolar recruitment.

Non-invasive ventilation (Non-invasive Positive Pressure Ventilation or NIPPV)

This refers to all modalities that assist ventilation without the use of an endotracheal tube. Non-invasive ventilation is primarily aimed at minimizing patient discomfort and the complications associated with invasive ventilation. It is often used in cardiac disease, exacerbations of chronic pulmonary disease, sleep apnea, and neuromuscular diseases. Non-invasive ventilation refers only to the patient interface and not the mode of ventilation used; modes may include spontaneous or control modes and may be either pressure or volume modes.

Some commonly used modes of NIPPV include:

Proportional Assist Ventilation (PAV)

Proportional Assist Ventilation (PAV) is a form of synchronised ventilator support based upon the Equation of Motion in which the ventilator generates pressure in proportion to the instantaneous patient effort. Unlike other modes of partial support, there is no target flow, tidal volume or pressure. PAV’s objective is to allow the patient to attain ventilation and breathing pattern his ventilatory control system desires. The main operational advantages of PAV are automatic synchrony with inspiratory efforts, exhalation and adaptability to change in ventilatory demand.

Proportional Assist Ventilation Plus — PAV+ (Puritan Bennett – 840 ventilator range, Proportional Pressure Support — PPS (Drager Evita series)and Respironics BiPAP Vision PAV , are commercially available implementations of PAV which automatically amplify the patient's own spontaneous effort to breathe by increasing airway pressure during inspiration proportionally to a set amplification factor.
In PAV+, the level of amplification, thus the level of work of breathing, is set through a single setting (%support) and the pressure applied is continuously and automatically adjusted based on measures (including automatic assessment of Elastance and Resistance) taken throughout the inspiratory cycle to maintain an appropriate level of support.

Adaptive Support Ventilation (ASV)

Adaptive Support Ventilation (ASV) is a positive pressure mode of mechanical ventilation that is closed-loop controlled. In this mode, the frequency and tidal volume of breaths of a patient on the ventilator are automatically adjusted based on the patient’s requirements. The lung mechanics data are used to adjust the depth and rate of breaths to minimize the work rate of breathing. In the ASV mode, every breath is synchronized with patient effort if such an effort exists, and otherwise, full mechanical ventilation is provided to the patient.

ASV technology was originally described as one of the embodiments of US Patent No. 4986268.[5] In this invention, a modified version of an equation derived in physiology in 1950 [6] to minimize the work rate of breathing in man, was used for the first time to find the optimum frequency of mechanical ventilation. The rationale was to make the patient's breathing pattern comfortable and natural within safe limits, and thereby stimulate spontaneous breathing and reduce the weaning time. A prototype of the system was built by the inventor in late 1980s. The inventor is Dr. Fleur T. Tehrani who is a university professor in the US. Shortly after the Patent was issued in 1991, Hamilton Medical, a ventilator manufacturing company, contacted the inventor and discussed marketing the technology with her. Some years later, Hamilton Medical marketed this closed-loop technique under license of this Patent as ASV.

Since the issuance of the Patent, a number of articles have been published by the inventor and her colleagues that are related to the invention, and some of them describe further advancements of the closed-loop techniques presented in the Patent.[7]

Neurally Adjusted Ventilatory Assist (NAVA)

Neurally Adjusted Ventilatory Assist (NAVA) is a unique positive pressure mode to mechanical ventilation based on neural respiratory output, in connections with invasive and non-invasive NAVA.

The act of taking a breath is controlled by the respiratory center of the brain, which decides the characteristics of each breath, timing and size. The respiratory center sends a signal along the phrenic nerve, excites the diaphragm muscle cells, leading to muscle contraction and descent of the diaphragm dome. As a result, the pressure in the airway drops, causing an inflow of air into the lungs.

With NAVA, the electrical activity of the diaphragm (Edi) is captured, fed to the ventilator and used to assist the patient's breathing in synchrony with and in proportion to the patients own efforts, regardless of patient category or size. As the work of the ventilator and the diaphragm is controlled by the same signal, coupling between the diaphragm and the SERVO-i ventilator is synchronized simultaneously. Reference: New method permits neural control of mechanical ventilation

Choosing amongst ventilator modes

Assist-control mode minimizes patient effort by providing full mechanical support with every breath. This is often the initial mode chosen for adults because it provides the greatest degree of support. In patients with less severe respiratory failure, other modes such as SIMV may be appropriate. Assist-control mode should not be used in those patients with a potential for respiratory alkalosis, in which the patient has an increased respiratory drive. Such hyperventilation and hypocapnia (decreased systemic carbon dioxide due to hyperventilation) usually occurs in patients with end-stage liver disease, hyperventilatory sepsis, and head trauma. Respiratory alkalosis will be evident from the initial arterial blood gas obtained, and the mode of ventilation can then be changed if so desired.

Positive End Expiratory Pressure may or may not be employed to prevent atelectasis in adult patients. It is almost always used for pediatric and neonatal patients due to their increased tendency for atelectasis.

High frequency oscillation is used most frequently in neonates, but is also used as an always alternative mode in adults with severe ARDS.

Pressure Regulated Volume Control is another option.

Initial ventilator settings

The following are general guidelines that may need to be modified for the individual patient.

Tidal volume, rate, and pressures

As the amount of tidal volume increases, the pressure required to administer that volume is increased. This pressure is known as the peak airway pressure. If the peak airway pressure is persistently above 45 cmH2O (4.4 kPa) for adults, the risk of barotrauma is increased (see below) and efforts should be made to try to reduce the peak airway pressure. In infants and children it is unclear what level of peak pressure may cause damage. In general, keeping peak pressures below 30 cmH2O (2.9 kPa) is desirable.

Monitoring for barotrauma can also involve measuring the plateau pressure, which is the pressure after the delivery of the tidal volume but before the patient is allowed to exhale. Normal breathing pattern involves inspiration, then expiration. The ventilator is programmed so that after delivery of the tidal volume (inspiration), the patient is not allowed to exhale for a half a second. Therefore, pressure must be maintained in order to prevent exhalation, and this pressure is the plateau pressure. Barotrauma is minimized when the plateau pressure is maintained < 30–35 cmH2O.

Sighs

An adult patient breathing spontaneously will usually sigh about 6–8 times per hour to prevent microatelectasis, and this has led some to propose that ventilators should deliver 1½–2 times the amount of the preset tidal volume 6–8 times per hour to account for the sighs. However, such high quantity of volume delivery requires very high peak pressure that predisposes to barotrauma. Currently, accounting for sighs is not recommended if the patient is receiving 10-12 mL/kg or is on PEEP. If the tidal volume used is lower, the sigh adjustment can be used, as long as the peak and plateau pressures are acceptable.

Sighs are not generally used with ventilation of infants and young children.

Initial FiO2

Because the mechanical ventilator is responsible for assisting in a patient's breathing, it must then also be able to deliver an adequate amount of oxygen in each breath. The FiO2 stands for fraction of inspired oxygen, which means the percent of oxygen in each breath that is inspired. (Note that normal room air has ~21% oxygen content). In adult patients who can tolerate higher levels of oxygen for a period of time, the initial FiO2 may be set at 100% until arterial blood gases can document adequate oxygenation. An FiO2 of 100% for an extended period of time can be dangerous, but it can protect against hypoxemia from unexpected intubation problems. For infants, and especially in premature infants, avoiding high levels of FiO2 (>60%) is important.

Positive end-expiratory pressure (PEEP)

PEEP is an adjuvant to the mode of ventilation used to help maintain functional residual capacity (FRC). At the end of expiration, the PEEP exerts pressure to oppose passive emptying of the lung and to keep the airway pressure above the atmospheric pressure. The presence of PEEP opens up collapsed or unstable alveoli and increases the FRC and surface area for gas exchange, thus reducing the size of the shunt. For example, if a large shunt is found to exist based on the estimation from 100% FiO2 (see above), then PEEP can be considered and the FiO2 can be lowered (< 60%) in order to maintain an adequate PaO2, thus reducing the risk of oxygen toxicity.

In addition to treating a shunt, PEEP may also be useful to decrease the work of breathing. In pulmonary physiology, compliance is a measure of the "stiffness" of the lung and chest wall. The mathematical formula for compliance (C) equals change in volume divided by change in pressure. The higher the compliance, the more easily the lungs will inflate in response to positive pressure. An underinflated lung will have low compliance and PEEP will improve this initially by increasing the FRC, since the partially inflated lung takes less energy to inflate further. Excessive PEEP can however produce overinflation, which will again decrease compliance. Therefore it is important to maintain an adequate, but not excessive FRC.

Indications. PEEP can cause significant haemodynamic consequences through decreasing venous return to the right heart and decreasing right ventricular function. As such, it should be judiciously used and is indicated for adults in two circumstances.

If used, PEEP is usually set with the minimal positive pressure to maintain an adequate PaO2 with a safe FiO2. As PEEP increases intrathoracic pressure, there can be a resulting decrease in venous return and decrease in cardiac output. A PEEP of less than 10 cmH2O (1 kPa) is usually safe in adults if intravascular volume depletion is absent. Lower levels are used for pediatric patients. Older literature recommended routine placement of a Swan-Ganz catheter if the amount of PEEP used is greater than 10 cmH2 for hemodynamic monitoring. More recent literature has failed to find outcome benefits with routine PA catheterisation when compared to simple central venous pressure monitoring.[8] If cardiac output measurement is required, minimally invasive techniques, such as oesophageal doppler monitoring or arterial waveform contour monitoring may be sufficient alternatives.[9][10] PEEP should be withdrawn from a patient until adequate PaO2 can be maintained with a FiO2 < 40%. When withdrawing, it is decreased through 1–2 cmH2O decrements while monitoring haemoglobin-oxygen saturations. Any unacceptable haemoglobin-oxygen saturation should prompt reinstitution of the last PEEP level that maintained good saturation.

Positioning

Prone (face down) positioning has been used in patients with ARDS and severe hypoxemia. It improves FRC, drainage of secretions, and ventilation-perfusion matching (efficiency of gas exchange). It may improve oxygenation in > 50% of patients, but no survival benefit has been documented.

Sedation and Paralysis

Most intubated patients receive intravenous sedation through a continuous infusion or scheduled dosing to help with anxiety or psychological stress. Sedation also helps the patient tolerate the constant irritation of the endotracheal tube in their mouth, pharynx and trachea. Without some form of sedation and analgesia, it is common for patients to "fight" the ventilator. This fighting increases work of breathing and may cause further lung injury. Daily interruption of sedation is commonly helpful to the patient for reorientation and appropriate weaning. These interruptions are frequently described as "sedation vacations" and have been shown to reduce the time patients stay on mechanical ventilation.[11]

It is not uncommon for patients on a mechanical ventilator to be given a muscle relaxant or paralytic to aid in ventilation. These "neuromuscular blockades" prevent skeletal muscle from contracting and thereby stop all patient movement including respiratory efforts. These types of pharmaceutical agents must always be given in conjunction with sedation as the effects of the paralytics is not only uncomfortable but would cause significant psychological stress and anxiety.

Prophylaxis

Modification of settings

In adults when 100% FiO2 is used initially, it is easy to calculate the next FiO2 to be used and easy to estimate the shunt fraction. The estimated shunt fraction refers to the amount of oxygen not being absorbed into the circulation. In normal physiology, gas exchange (oxygen/carbon dioxide) occurs at the level of the alveoli in the lungs. The existence of a shunt refers to any process that hinders this gas exchange, leading to wasted oxygen inspired and the flow of un-oxygenated blood back to the left heart (which ultimately supplies the rest of the body with unoxygenated blood).

When using 100% FiO2, the degree of shunting is estimated by subtracting the measured PaO2 (from an arterial blood gas) from 700 mmHg. For each difference of 100 mmHg, the shunt is 5%. A shunt of more than 25% should prompt a search for the cause of this hypoxemia, such as mainstem intubation or pneumothorax, and should be treated accordingly. If such complications are not present, other causes must be sought after, and PEEP should be used to treat this intrapulmonary shunt. Other such causes of a shunt include:

When to withdraw mechanical ventilation

Withdrawal from mechanical ventilation—also known as weaning—should not be delayed unnecessarily, nor should it be done prematurely. Patients should have their ventilation considered for withdrawal if they are able to support their own ventilation and oxygenation, and this should be assessed continuously. There are several objective parameters to look for when considering withdrawal, but there is no specific criteria that generalizes to all patients.

Trials of spontaneous breathing have been shown to accurately predict the success of spontaneous breathing. (Yang K, Tobin MJ. A prospective study of indexes predicting the outcome of weaning from mechanical ventilation. N Engl J Med 1991;324:1445–1450).

Connection to ventilators

There are various procedures and mechanical devices that provide protection against airway collapse, air leakage, and aspiration:

Terminology

Terminology used in the field of mechanical ventilation and respiratory support:

See also

References

  1. Colice, Gene L (2006). "Historical Perspective on the Development of Mechanical Ventilation". In Martin J Tobin. Principles & Practice of Mechanical Ventilation (2 ed.). New York: McGraw-Hill. ISBN 978-0071447676. 
  2. Chamberlain D (2003) "Never quite there: A tale of resuscitation medicine" Clinical Medicine, Journal of the Royal College of Physicians' 3 6:573-577
  3. "Smother Small Dog To See it Revived. Successful Demonstration of an Artificial Respiration Machine Cheered in Brooklyn. Women in the Audience, But Most of Those Present Were Physicians. The Dog, Gathered in from the Street, Wagged Its Tail.". New York Times. May 29, 1908, Friday. http://en.wikipedia.org/wiki/Image:Poe_1908May29.gif. Retrieved 2007-12-25. "An audience, composed of about thirty men and three or four women, most of the men being physicians, attended a demonstration of Prof. George Poe's machine for producing artificial respiration in the library of the Kings County Medical Society, at 1,313 Bedford Avenue, Brooklyn, last night, under the auspices of the First Legion of the Red Cross Society." 
  4. Expiratory Asynchrony. By Hong-Lin Du and Yoshitsugu Yamada, Respiratory Care Clinics of North America 2005;11:265-280.
  5. Tehrani, F. T., “Method and Apparatus for Controlling an Artificial Resirator,” US Patent No. 4986268, issued Jan. 22, 1991.
  6. Otis, A. B., Fenn, W. O., Rahn, H. "Mechanics of Breathing in Man." Journal of Applied Physiology, Volume 2: 592-607, 1950.
  7. See other references under further readings
  8. Shah, MR et al. Impact of the pulmonary artery catheter in critically ill patients: meta-analysis of randomized clinical trials. JAMA. 2005 October 5;294(13):1664-70. PMID: 16204666
  9. Vallee F, et al. Stroke output variations calculated by oesophageal Doppler is a reliable predictor of fluid response. Intensive Care Med. 2005 Oct;31(10):1388-93. Epub 2005 August 19. PMID: 16132887
  10. Uchino S, et al. Pulmonary artery catheter versus pulse contour analysis: a prospective epidemiological study. Crit Care. 2006 December 14;10(6):R174 [Epub ahead of print] PMID: 17169160
  11. Kress JP, Pohlman AS, O'Connor MF, Hall JB. Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation. New England Journal of Medicine. May 18 2000;342(20):1471–1477.
  12. Critical Care | Full text | Rapid shallow breathing index—a key predictor for noninvasive ventilation

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