The COVID-19 pandemic has raised some questions about the use of positive pressure ventilatory devices and an important question has arisen as to whether negative pressure ventilatory support may be useful in the treatment of COVID-19 patients, both in terms of noninvasive ventilation using continuous negative extra-thoracic pressure (CNEP), and actual cycling negative pressure ventilation (NPV).
Historical review and perspective
Breathing is an unconscious act which is automatic and to which we give little thought, until we develop disease which gives rise to breathlessness, distress, exhaustion, and threatens our lives. Normal breathing is produced by negative pressure developing in the thoracic cavity by the action of our inspiratory muscles contracting and distending the rib cage in combination with descent of the diaphragm. This creates a gradient from the higher atmospheric pressure and causes air to flow via the upper airway into elastic lungs. Relaxation of these muscles allows recoil of the lungs and chest wall to produce exhalation.
Throughout most of the 19th century and the first half of the 20th century, negative pressure ventilatory devices were those most commonly used to provide ventilatory assistance. A common misconception amongst the present generation of anesthetists, critical care doctors, and nurses, is that this form of respiratory support was only useful for the well-known polio epidemics of the 20th century. This view is incorrect.
John Mayow, an English scientist and physician built the first external negative pressure ventilatory device in 1673. The unit used a bellows and bladder to expel the air and Mayow described this as mimicking the action of the respiratory muscles.
The first tank-type respirator was described by a Scottish doctor, John Dalziel, in 1838. Dalziel thought that by applying a negative pressure to the body rhythmically, in phase with inspiration, he might be able to prevent the deaths of patients who were suffering from respiratory failure. He designed and constructed an airtight box in which the patient was seated with the head and neck outside. He created the negative pressure by a pair of bellows worked from the outside by a one-way valve and piston system. Two windows in the side of the box allowed observation of the patient’s chest movements. We do not have any details of this in clinical practice although we know that it was used by Lewins in 1840 to try and resuscitate a drowned seaman whose body was brought to him. Lewins observed that “the dead body was made to breathe in such a manner as to lead the bystanders to suppose that the unfortunate individual was restored to life.”
It was >30 years later before others followed. Alfred Jones, USA, invented a body enclosing iron tank device [Fig. 1] in 1864.
Von Hauke, in 1874 Austria, developed a cuirass-type device first and subsequently a tank device. Working with his colleague, Waldenburg, Von Hauke had been using continuous positive pressure applied to the mouth by a facemask for periods of up to 15 minutes in the treatment of patients with atelectasis, pneumonia, and emphysema. Von Hauke thought that a continuous negative pressure cuirass device would achieve similar results and applied intermittent negative pressure in phase with inspiration to try and assist cases of respiratory failure. He found the cuirass device unsuitable in both children and adults who were agitated. He then designed a tank respirator to cover the whole body of the patient. He tried this tank device [Fig. 2] on many types of respiratory disease, neonatal asphyxia, pneumonia, atelectasis, tracheitis, diphtheria, and croup, treating patients for 2 to 3 hours at a time. Waldenburg clearly describes the remarkable case of a small girl with “great debilitation and chronic double pneumonia” who was treated in the tank for 3 months and despite her seemingly hopeless prognosis she slowly improved, gained weight, and the obvious deformity of her chest wall resolved.
Woillez[7,8] produced the first French tank respirator in 1876, called the Spirophore [Fig. 3]. This device had an adjustable rubber seal around the neck. The protruding head rested on a shelf and the unit had a sliding platform for the patient to lie on. This basic structure became the prototype for all subsequent negative pressure tank units. He had been experimenting for almost 20 years on cadaver lungs in a sealed metal vessel attached to a bellows with the trachea opened to the atmosphere. He employed an early type of endoscope to allow observation of the lungs. Interestingly, several of his contemporaries had tried to produce the same results in cadavers by positive pressure inflation of the lungs. Woillez maintained that this was on unphysiological, i.e. not characteristic of normal respiratory function in man, a comment also made by an eminent Critical Care physician recently during the COVID-19 pandemic.
In 1854, Woillez enunciated two important principles from his research:
- In life, air enters the lungs at a pressure not greater than atmosphere. In artificial respiration much greater pressures are used.
- The primary reason for the entry of air into the lungs is not the pressure of the air but the expansion of the thoracic cavity by the respiratory muscles.
Breuillard of France patented a tank type respirator in 1887. Alexander Graham Bell, inventor of the telephone, became interested in the problems of artificial respiration. His son, Edward, had died the day after his birth. Bell studied normal respiration and invented a negative pressure vacuum jacket which was comprised of a rigid shell in two halves which strapped around the chest. No clinical records exist for either of these devices.
In 1901, Rudolf Eisenmenger, Hungary, patented a portable respirator, comprised of a simple box in two halves which enclosed the patient’s abdomen and chest. He stressed the fact that this device was portable and gave access to the patient’s throat and limbs. Initially the device was hand-operated but he subsequently developed a motorized device and although we have no precise clinical records, it was apparently successful [Figures 4 and 5].
Eisenmenger also developed an early cuirass shell device extending from the upper sternum to the pelvis in 1904. The shell was attached to a foot-operated bellows. Alternating positive and negative pressures were applied to the thorax and abdomen. A motorized version of this was subsequently produced.[12,13]
Davenport, in 1905 London, developed early types of iron lung, with patients sitting or lying, but using hand-operated bellows to create negative pressure which limited their success.
In 1918 two physiologists, Chillingworth and Hopkins described the successful use of an electrically powered body plethysmograph to ventilate dogs that had been tracheotomized. They alternated the pressure within the device and studied the effects of the lung expansion on the circulation. Although they did not realize the significance of their alternating positive and negative pressure system for use in humans, it reportedly inspired Drinker[17,18] in his work to produce the first fully working iron lung.
In the first half of the 20th century, poliomyelitis causing respiratory failure had a mortality of almost 100% in children and young adults. Steuart, in 1918, from South Africa, designed a rigid airtight wooden box around the child’s thorax and abdomen with a large bellows driven by an electric motor to provide intermittent negative pressure. It was the first workable cuirass device aimed at maintaining artificial respiration with adjustable tidal breath and minute volume. It did not undergo clinical trials.
NPV became a true clinical reality in 1928 with the development of the iron lung, which was initially designed and built by an engineer, Phillip Drinker, a pediatrician Charles McKhann, and Louis Shaw, a physiologist.[17,18] This was the first reliable method of prolonged respiratory support and had taken several years of work in the Department of Ventilation, Illumination, and Physiology, of the Harvard Medical School. Although subsequently associated with the polio epidemic, it was initially designed for the Consolidated Gas Company of the USA, who needed resuscitation and respiratory support equipment for a substantial number of workers who were being injured by electric shock, carbon monoxide gas, and smoke inhalation. They engaged Dr Cecil Drinker, professor of Physiology at the Harvard School of Public Health and he called on his brother, engineer Philip Drinker, to undertake the research. Initially they experimented by placing curare-paralyzed cats in iron boxes with their heads protruding through a rubber collar, negative pressures were generated by a hand operated syringe mechanism, and pressure measurements within the device were correlated with the volumes of air moved in the cats. In 1927, they showed that alternating negative pressure and release kept the paralyzed cats alive for several hours.
This research and the increasing problems of polio epidemics led to the team constructing a unit large enough to accommodate children and adults. Their apparatus consisted of a cylindrical metal chamber large enough to accommodate the patient’s entire body, except for the head [Fig. 6]. The patient lay on a mattress supported on an iron frame fastened rigidly to the lid of the tank. The frame and lid rolled in and out of the tank on wheels. Airtight closure of the chamber was produced by levers around the rim of the lid and a rubber collar around the patient’s neck. The collar was made in different sizes. The head rested on an adjustable support attached to the outside of the tank. The tank could be rotated approximately 75° in both directions and the foot end raised or lowered 15° providing the patient with a change in position. The body of the tank was equipped with marine-type glass portholes for observation and there were numerous small holes for inserting thermometers, connections for blood pressure cuffs, or stethoscopes.
Initially, two high-speed electric blowers alternatively removed air from the tank and then blew it back in. Any combination of pressure could be applied, positive or negative, up to about 60 cm of water. The breathing rate could be adjusted, ranging from 10 to 40 per minute.
Drinker and his team undertook a series of experiments on normal men and women chosen at random from the laboratory personnel. Minute volumes were calculated for a variety of negative and positive pressures and compared with the increase above normal. They concluded that the average threshold pressures, those which induce breathing beyond the subjects will, were found to be only 5 to 10 cm of water for normal men and women.
The pumps were subsequently replaced by a bellows-type device and the original design underwent multiple refinements over the next 25 years. The introduction of this respirator coincided with reliable electricity becoming available on the two coasts of the USA and subsequently throughout the country.[19,20]
The Drinker design was expensive, bulky, complex, and rather cumbersome to use. In 1931, John Emerson modified and improved the unit making it available for less than half the cost. His new design was lighter and had a notable additional innovation of an airtight transparent dome for the head of the patient, so that intermittent positive pressure could be given to the patient while the remainder of the unit could be opened for unhurried nursing care. This new unit had more glass side ports and large rectangular metal doors on both sides to aid the care of the patient. Blood could be taken easily and clinical observations made. A substantial leather diaphragm was moved by power from a standard cycling vacuum cleaner pump. Two vacuum pumps could be coupled to amplify the pressures. It could also be manually operated if there was a power failure.
Emerson deliberately chose not to patent his design, so that these cheaper units could be made quickly throughout the USA. Accommodation of these tank ventilators into single large rooms formed the first dedicated respiratory care units. Emerson published a pamphlet “the evolution of iron lungs” which contained a number of pictures of previously designed negative pressure tank ventilators, as described above, long before the introduction of the Drinker model.
Drinker and the Harvard University sued Emerson for infringement of their patents, but Emerson won the case. The judge agreed with Emerson that a technology that saved lives should be shared by everyone, a point that is relevant to the current COVID-19 pandemic.
Negative pressure ventilatory devices continued to be developed and widely used throughout the world in countries wealthy enough to build or buy them, notably for the poliomyelitis epidemics between 1930 and 1960. Some patients who were unable to regain independent breathing were continuously or nocturnally supported on these devices for >60 years. Some of these patients wrote moving accounts of their lives in books, newspapers, and magazines, so it is hardly surprising that a whole generation of people and doctors associate tank ventilators with poliomyelitis.[22–24]
When a serious polio epidemic broke out in Australia in 1937, the cost of buying Drinker respirators and transporting from America was so high that the South Australian Health Department asked an engineer, Edward Both, to design a cheaper alternative.[25,26] The Both portable cabinet respirator was made with plywood and was easy to construct, transport, and use [Fig. 7]. Doctors and nurses could quickly become familiar with the device and hospitals built their own versions for less than £100, factors again relevant to our present-day situation with COVID-19.
When a severe epidemic of poliomyelitis occurred in the UK in 1938 and ventilators were in short supply, William Morris (Lord Nuffield), was so impressed with the Both design that he ordered them to be built at his car manufacturing plant in the UK and donated to regional hospitals around the country and Commonwealth. In the early 1950s >700 Both–Nuffield devices were being used in the UK hospitals.
Morris asked Sir Robert Mackintosh, head of the Department of Anaesthesia at Oxford, to undertake the distribution of the Both design and to teach their use through daily demonstrations at the Radcliffe Clinic in Oxford. This led to Macintosh using the Both cabinet respirator to manage postoperative surgical patients as well. In 1940, he demonstrated the prevention of postoperative atelectasis by using the Both cabinet respirator. This was an initial example of critical care medicine providing respiratory support and paved the way for the establishment of Critical Care units.
However, the considerable space requirements and nursing care demands were problems in using this large bulky equipment.
In 1960, Kelleher introduced a modification of the basic iron lung design, allowing it to be rotated 180°. This automatic turning helped to treat or prevent atelectasis, and in addition to polio, he used it successfully for the treatment of Guillain–Barre syndrome.
An important further development was a design by Sunny Weingarten in 1975. He had been a polio survivor from the age of 7 and designed a lighter, more portable tank, the “Portalung.” It was made from fiberglass and therefore much lighter, the adult size being approximately 45 kg. It was subsequently made in four sizes between 33 inches and 71 inches in length for children and adults. It was flexible in terms of being able to use several brands of modern vacuum pumps, accommodating pressures ranging from −60 cm H2O to +20 cm and respiratory rates of 4 to 60 breaths/minute. Weingarten travelled throughout the USA, eventually reaching all 48 states. Initially he used the device full-time but in the middle part of his life was able to use it only at night. In the latter part of his life, he required full-time ventilation again. He died at the age of 70 in 2012. The “Portalung” was patented and FDA approved.
Cuirass-type negative pressure devices
The problems related to the large tank devices promoted a wide variety of cuirass type ventilators. These covered the chest only, or the chest and abdomen. As a consequence of the resemblance to mediaeval protective chest armor they were given the name of cuirass. The earlier models only allowed for anterior expansion of the chest wall. Some ended at the waist, limiting diaphragmatic descent. Others actually compressed the anterior abdominal wall during inspiration. Lateral expansion was severely limited by units that were flush with the lateral chest wall and at times the apices of the lungs were excluded by the configuration. If the respiratory support needs of the patient were low, these neck to waist models could be adequate and they had the notable advantages of portability, freedom of the pelvis and extremities for nursing, lower costs, and less claustrophobia. Many patients could be adequately ventilated in a near sitting position.
As noted above, the first of these types of unite was made by Von Hauke in Austria in 1874.[5,6] Further developments throughout the 1930s included Sahlin’s[30,31] machine from the Physiology Institute in Lund, Sweden, the Peterson’s Pulsatorgurtel, also from Lund, and the Burstall’s jacket cuirass developed in Melbourne, Australia in 1938. In the late 1940s several new cuirasses were developed in America notably Blanchard’s Portable Plastic Respirator,[34,35] the Chestspirator, the Fairchild–Huxley chest respirator, and the Monaghan portable respirator.
The severe poliomyelitis epidemic in Copenhagen, Denmark, in 1952 became a turning point for the treatment of respiratory paralysis. Lassen described how the Blegdam Hospital in Copenhagen had 2722 admissions for acute poliomyelitis in a 19-week period, 866 of the paralytic type, necessitating ventilation in 316 patients. On one day, 70 patients needed a ventilator at the same time, with only one tank and six cuirasses available. A similar situation to this is now being seen with the COVID-19 pandemic in many countries.
Lassen reported that intermittent positive pressure ventilation (IPPV) was a more versatile method of artificial respiration at that time when negative pressure devices were in short supply. In collaboration with his anesthetist colleague, Ibsen, he developed the technique of tracheostomy and manual IPPV. The requirements in the COVID-19 pandemic are those of a new lethal virus but they are not an entirely new situation. The irony has been a shortage, or absence, of positive pressure devices in many countries.
It was simply a matter of time before physicians during the 1950s saw the potential use for noninvasive positive pressure support in other settings. This, combined with the fact that cuirass devices were often unable to adequately ventilate patients as a consequence of poor fit, obesity, or poor performance, led to their decreasing use. The ongoing development of positive pressure devices meant that few continued to advocate the use of NPV in the acute stages of respiratory disease. As a consequence, a whole generation of anesthetists and critical care doctors have been trained with little knowledge or experience of the potential benefits of negative pressure devices.
With the success of the polio vaccine, there was a dramatic reduction in the need for negative pressure ventilators resulting in them being stored or discarded. However, some physicians became increasingly interested in treating respiratory compromise from other disorders such as kyphoscoliosis, post-tuberculous thoracoplasty, pulmonary fibrosis, bronchiectasis, chronic obstructive pulmonary disease (COPD), and other neuromuscular disorders. As antibiotic therapy became more widely used in the 1950s and 1960s, patients recovered from devastating infections but were left persistently dyspneic and hypercapnic. As a consequence of limited availability of new positive pressure devices some centers began reusing iron lungs that were still available, to treat chronic respiratory failure and relieve intractable dyspnea. They felt that this form of ventilation was more physiological and that the lungs would not be further damaged by NPV. If the respiratory muscles were still too weak, or the chest walls less compliant, the benefit from NPV would be its reduction in the work of breathing, while supporting gas exchange and relieving dyspnea, all relevant considerations in many of the patients requiring ventilatory support in COVID-19 pneumonia.
Physiological research into NPV − 1950s onward
The 1950s saw the advent of notable physiological research into the performance of cuirass and tank devices. Plum and Lukas[41,42] in 1951, at Cornell compared the cuirass directly with a tank device in 10 cases of poliomyelitis. They found that the tank respirator produced greater tidal volumes at equivalent negative pressures with up to 100% improvement on the cuirass device.
Bryce-Smith and Davies, in 1954, undertook spirometry studies on six intubated paralyzed unconscious adult patients to determine tidal volumes obtained in a tank respirator, cuirass respirator, and rocking bed respirator at 20° to 40° both prone and supine. They found that tidal volumes above 350 mL were easily obtained in the Emerson tank subjects, obtainable but with considerable technical difficulties with the Monaghan cuirass respirator, and unobtainable and unsatisfactory with the McKesson rocking bed device.
Collier and Affeldt, in 1954, tested 14 adult patients with vital capacities of ≤250 mL and compared their respiratory performance in a tank device, thoracoabdominal cuirass shell, and a simple thoracic cuirass shell. They also found that the tidal volume produced by the tank ventilator was 40% greater than the thoracoabdominal cuirass and 53% better than the thoracic cuirass.
In a landmark paper in 1955, Pask stated that he hoped further development of the cuirass respirator would occur because this basic design must cause less compromise of the circulation than other types of positive pressure respirator, but would need to be made comfortable enough for use over long periods and capable of adequate ventilation of all patients. Of note he felt that it should be modified so that it would be possible to nurse the patient in the prone position and that the future for this type of respirator would be important. Pask’s comments from 1955 are still pertinent today.
Spalding and Opie, in 1954, evaluated the Tunnicliffe breathing jacket on patients with poliomyelitis who already had a tracheostomy and cuffed tracheostomy tube in place. The jacket proved to be more efficient than cuirass devices available at the time, but less effective than tank respirators and the new intermittent positive pressure devices.
While most of the initial physiology research involved patients with poliomyelitis, Kinnear et al., in 1988, looked at 25 subjects with chest wall disease giving rise to nocturnal hypoventilation. These patients had varying degrees of scoliosis, neuromuscular disorders, and post-thoracoplasty problems. Their results showed no change in cardiac output and synchronous rib cage and abdominal expansion with improved respiratory parameters.
During the 20th century, polio epidemics ventilator assistance for polio victims, who typically had normal healthy lungs but reduced power to breathe, simply required inflation of their relatively compliant lungs, allowing them to deflate spontaneously under their own elastic recoil. Both positive pressure ventilation (PPV) and NPV were only required to inflate the lung and then “switch off.” Since then different categories of patients (notably those with acute respiratory distress syndrome, ARDS) have posed challenges that have been managed mainly with increasingly sophisticated continuous positive airway pressure (CPAP), bilevel positive airway pressure, and IPPV devices. PPV technology has been developed while NPV has not undergone further evaluation in most centers.
Unknown to many modern critical care and anesthetic hospital units, is the fact that over the last 40 years others have remained active in the use of negative pressure noninvasive ventilation and some have made their own version of tank ventilators. Sauret et al. working in Barcelona, Spain, and Corrado and Gorini[50–53] in Florence, Italy, continued to assess noninvasive NPV and PPV for both acute and chronic respiratory failure. Corrado and Gorini summarized the literature on the use of both negative and positive forms of noninvasive ventilation in 2002. The primary end points in their assessment were progression to intubation or tracheostomy. Their research showed no difference between negative and positive modalities and no difference in mortality.
The main problems with continuing to use iron lungs were the nursing procedures, (the major factor) bulk, weight, and hospital space requirements, as noted previously.
Animal[54–57] and volunteer[43,58–60] research studies continued to modernize clinical NPV devices, and developed CNEP therapy to replace CPAP,[61,62] as well as introducing negative end-expiratory pressure (NEEP), to replace positive end-expiratory pressure (PEEP), either in combination with PPV[63–65] or with NPV.[61,62,66]
These modalities have been used to treat critically ill patients including ARDS, many more with acute respiratory failure against a background of COPD, and severe head and lung trauma.[51,67–69] Whole-tank NPV devices were also developed to treat infants and young children with a range of respiratory failure, using both CNEP and NPV + NEEP.
Could negative pressure ventilatory devices have a role in COVID-19 infection?
As outlined above, there is substantial evidence that both CNEP and NPV can deliver treatment to patients with ARDS as well as, or superior to, conventional PPV.
Avoiding intubation and PPV?
Our increasing understanding of the pathophysiology of COVID-19 has suggested that we consider avoiding intubation and positive pressure mechanical ventilation as it may have deleterious effects on pulmonary and cardiac function. Huang et al., in May 2020, reported in vitro studies showing that expression of angiotensin-converting enzyme (ACE2) in alveolar cells is increased following mechanical stretch and inflammation. Critically-ill COVID-19 patients have often required prolonged mechanical ventilation with positive pressure devices, which can cause mechanical stress to lung tissue. They analyzed transcriptome datasets of 480 (non-COVID-19) lung tissue samples in the GTex(Public GTEx database of human tissue gene expression profiles, USA https://www.gtexportal) tissue gene expression database and found that mechanical ventilation of the tissue donors increased the expression of ACE2 by more than two-fold (P < 10-6). They also proposed that mechanical ventilation of patients with COVID-19 pneumonia may eo ipso facilitate viral propagation in the lung, further accelerating the pulmonary pathology that had necessitated mechanical ventilation in the first place. Their findings support the call for gentler ventilation methods and protocols.
In addition to pulmonary function, the importance of maintaining cardiac output is essential, so that arterial blood can optimally deliver oxygen to the tissues.
The deleterious effects of COVID-19 on the cardiovascular system have been stressed in much of the recent COVID-19 literature from China, Italy, and the USA,[72–80] in which acute myocardial injury and chronic damage to the cardiovascular system have been reported. A potential consequence of using PPV is that by forcing air into lungs, which share the limited space within the chest, it inevitably increases the pressure on the heart and the major veins leading to it. Martin, in May 2020, writing on novel approaches to intensive care medicine, proposed that high levels of PEEP increase intrathoracic pressure, reducing venous return to the heart and may be a factor in the increasing incidence of thromboembolic events in the lungs.
Ng et al. assessed awake prone positioning for nonintubated oxygen-dependent COVID-19 pneumonia patients and concluded that with critical care teams globally facing resource depletion, awake prone positioning can be a low-risk, low-cost maneuver helping patients with COVID-19 pneumonia to delay and reduce the need for intensive care. This advice mirrors that of Pask from 1955.
New negative pressure ventilatory support devices?
Two recent publications[83,84] have presented the continuing physiological research into CNEP and NPV describing the performance of new negative pressure ventilator support devices. These reports have confirmed that the physiological evidence accumulated from the 1950s onwards did demonstrate important factors which are relevant to the re-introduction of CNEP and NPV in an ultra lightweight, low-cost, comfortable, efficient, robust and safe device which allows excellent monitoring and easy nursing.
New devices should deliver CNEP alone, or CNEP and NPV +NEEP therapy, be as effective as CPAP or superior, easy to use outside of an intensive care unit, and prevent escalation to endotracheal intubation and the use of positive sophisticated positive pressure devices.
Physicians moved from using NPV to PPV in the 1960s, largely related to nursing issues and the availability of smaller positive pressure devices. Consequently, NPV has been largely disregarded since then. There are a generation of anesthetists and intensivists who are largely unaware of the research base and its continued use in children and adults. The scientific and clinical evidences show that a modern CNEP/NPV device with a tors-only cabinet may provide a noninvasive ventilation alternative to CPAP, with the additional possibility of preventing escalation of the patient to intubation and PPV. The ease of manufacture, use of readily available parts (not in competition with PPV devices), low cost, and easy nursing and medical management, including in the prone position, are important further considerations.
Financial support and sponsorship
Conflicts of interest
Prof David Howard is the voluntary, non-paid Chairman of the UK Exovent Charity, Charities Commission number 1189967.
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