The introduction of blood gases into clinical practice

Cover photo.

Blood gas calculator. Designed by John Severinghaus and marketed by Radiometer. Courtesy of the Wood Library-Museum of Anesthesiology, Schaumburg, IL, USA.

The anesthesiologist produces, in the course of his operating room duties, more and bigger disturbances in acid-base balance in a week than other physicians are apt to see in a year.

John Bunker ¹

In December 1958, a group of scientists and clinicians assembled in London for a Ciba-sponsored symposium on pH and blood gas measurement. The focus of the meeting was respiratory disorders of acid-base balance, particularly in relation to anaesthesia. Much of the meeting was highly technical but the aim was to provide an interface between scientists and clinicians. Experts like Poul Astrup, John Nunn and John Severinghaus contributed to the wide-ranging discussions that followed the presentations. These were included in the published proceedings, collating ‘a great deal of information which is widely scattered in journals’. ²

Blood gas analysis as a clinically useful tool was in its infancy. The discussion at the symposium highlighted the rapidly developing technology and ongoing debates, which would only intensify over the following years. ³ By the mid-1960s, the Americans and the Danes were locked in a ‘trans-Atlantic acid-base debate’ about the accuracy and relevance of base excess as a parameter. ¹ But while scientists debated, clinicians had to make use of the new diagnostic tool as best they could.

They were assisted by advances in commercial equipment. New blood gas analysers became available in the 1960s that could measure pH, as well as the partial pressure of oxygen (pO₂) and carbon dioxide (pCO₂). The complex nomograms required to interpret the results were simplified in 1966 by the development of a slide rule by John Severinghaus. This incorporated the existing nomograms on one side, as well as the haemoglobin dissociation curve on the other. ⁴ The accompanying booklet stated ‘The calculations used in connection with blood gas and expired air analysis, while mathematically simple, involve multiple constants, factors and equations.’ ⁵ While these ‘mathematically simple’ calculations occupied 22 pages of the booklet, the instructions for using the slide rule itself were more straightforward. The slide rule was manufactured by Radiometer and, in 1973, when they released the first commercially available, fully automated, microprocessor-controlled blood gas machine, the acid-base laboratory (ABL1), it was accompanied by the Severinghaus slide rule to assist with interpretation of results. ⁶

Even with these tools at their disposal, clinicians still required considerable knowledge to use blood gases in their practice. Moran Campbell, an English physician who later migrated to Canada, presented a number of clinical cases in the early 1960s, concluding that physicians were now ‘in the process of relearning respiratory physiology’. ⁷ Campbell played an important role in the early incorporation of respiratory physiology into clinical medicine. ⁸ In the 1950s there were increasing numbers of patients presenting with chronic bronchitis and respiratory failure, the consequences of a marked increase in smoking during the war years and the ever-worsening pollution. Many of these patients were treated in oxygen tents, where they became more peaceful but often fell into an irreversible sleep. After performing blood gas analysis on several patients, Campbell established that oxygen therapy in these patients led to a rapid rise in pCO₂, which was accompanied by a severe acidosis. ⁹ Using his knowledge of the haemoglobin–oxygen dissociation curve, he postulated that low concentrations of oxygen would relieve their symptoms and improve their tissue oxygenation, without the ensuing complications. As there was no equipment that could reliably deliver his desired inspiratory concentration of 24–35% oxygen, he designed a Venturi system which would entrain large flows of air with a low flow of oxygen. ¹⁰ Subsequent modifications led to a more accurate device which provided differing oxygen concentrations (24%, 28% and 35%) by varying the Venturi orifice. ¹¹ His other important contribution to respiratory medicine was to insist that patients’ respiratory function was assessed when they were well, so that when they deteriorated, clinicians aimed for the patient’s individual parameters, rather than trying to normalise their blood gases. ¹²

Meanwhile in the operating theatre, measuring blood gases was proving useful and instructive. A study of routine anaesthesia, conducted in 1969 in Vancouver, revealed considerable variations in blood gases. In all the spontaneously ventilating patients, arterial pCO₂ was found to have risen, sometimes as high as 70 mmHg. Significantly there were no clinical signs of hypercarbia, leading the author to conclude that watching the rebreathing bag, or even measuring tidal volumes was insufficient to prevent hypercarbia. Better carbon dioxide regulation was achieved in the thoracotomy patients who were manually ventilated at all times; even during one lung anaesthesia, carbon dioxide levels remained within normal limits. Preoperative arterial pO₂ showed such a wide variation in the patients studied that they concluded it should be an essential investigation in ‘major or seriously ill patients so that a baseline is available for comparison during and after anaesthesia’. ¹³

While early endobronchial tubes had been available since 1931, ¹⁴ the introduction of the Bjork and Carlens’ double lumen tube in 1950 ¹⁵ led to a rapid increase in thoracic surgery.^16,17 Blood gases became an important tool, providing information to both surgeons and anaesthetists. Blood gas analysis during endobronchial anaesthesia for pneumonectomy suggested that oxygenation was best maintained by delivering high concentrations of oxygen, ligating the pulmonary artery early in the operation and vigorously ventilating the dependent lung. ¹⁸

As diagnostic laparoscopy became increasingly popular in the early 1960s, surgeons began to perform more lengthy procedures via the laparoscope, such as biopsies, aspirations and tubal ligations. The combination of a tensely distended abdomen, carbon dioxide insufflation and steep head down position provided new challenges for anaesthetists. Early studies with endotracheal anaesthesia comparing spontaneously ventilating patients with controlled respiration, not surprisingly, showed a significant rise in arterial pCO₂ in those that were breathing spontaneously. The authors recommended ‘patients undergoing laparoscopy should breathe a gas mixture containing at least 50% oxygen, while ventilation is controlled with an endotracheal airway in place’. ¹⁹

Hypoxia in relation to anaesthesia attracted a great deal of attention. A 1972 review claimed that since the introduction of simplified blood gas analysis, around 300 papers had been published defining the incidence and factors responsible for hypoxaemia during and after anaesthesia. ²⁰ The paper had two attached appendices explaining the physiology, indicative of the detailed understanding now required by anaesthetists. They concluded that active prevention and reversal of airway collapse and atelectasis would address most causes of hypoxia. While recommending a number of important measures, they also noted ‘the specific technique is not as important as the recognition that it is a vital part of the anaesthetic and surgical experience’. ²⁰ Anaesthetists were advised to have a high index of suspicion and routinely measure arterial pO₂.

The ability to measure blood gases contributed greatly to the development of anaesthesia in the 1960s and 1970s, but the knowledge gained by anaesthetists, especially those practising in the fledgling area of intensive care, also contributed to the advancement of respiratory physiology. John Nunn, professor of anaesthesia at the University of Leeds and subsequent director of anaesthesia at Northwick Park Hospital, Middlesex, wrote the first edition of Applied Respiratory Physiology in 1969. Eight years later ‘important advances in pure and applied respiratory physiology’ had required the production of a new edition. ²¹ Interestingly, in this greatly expanded text, a few sections were excluded because ‘their content is now too familiar’. By 1977, basic knowledge of respiratory and acid-base physiology was regarded as essential for anaesthetists and physicians.

The introduction of non-invasive monitors such as oximetry and end-tidal carbon dioxide measurement from the 1980s onwards increased the information available to clinicians. But blood gas analysis, now a simple, rapidly performed test, remains a clinically important tool—and respiratory physiology, along with an understanding of acid-base physiology, remains a core part of the anaesthetic and intensive care curriculum.