Breathing, the Immune System and Major Surgery
“Remember to breathe. It is after all, the secret of life.” – Gregory Maguire, a lion among men (The Wizard of Oz)
Wim Hof, a 57 year old eccentric Dutchman who holds over 23 world records for cold exposure, climbing Everest in shorts, running a marathon in the Namib desert without water and swimming under ice, to name a few, will seem an unlikely candidate for a peri-operative topic.
Wim is helping scientists rewrite physiology textbooks by demonstrating that the hitherto considered “involuntary” autonomic nervous system can in fact be “voluntarily” influenced. This voluntary influence may lead to beneficial effects on the immune system.
So what does the immune system have to do with peri-operative outcomes?
Well, when the body suffers the traumatic insult of major surgery a systemic inflammatory response ensues. This triggers immunological, endocrinological and haematological responses. The initial response is via activation of the sympathetic nervous system (SNS) at the site of initial injury followed by the interacting response of the immunological and neuroendocrine systems which induce multiple endocrine and metabolic consequences.
The endocrine “stress response” follows from increased pituitary hormone secretion which have secondary effects on other target endocrine organs. The key net effect is an increased release of ACTH, growth hormone, AVP, cortisol, aldosterone, glucagon and a concomitant decrease in insulin and thyroxine. The metabolic effects of this combination is increased catabolism, with substrates mobilised to provide energy, and retention of salt and water to maintain fluid volume and haemodynamic stability.
Alongside these metabolic changes, immunological and haematological changes occur, involving cytokine production, an acute phase reaction, neutrophil leucocytosis and lymphocyte proliferation.
Cytokines mediate and maintain the inflammatory response to the local tissue injury as well as initiating some of the systemic changes. The key cytokines released following major surgery are interleukin-1 (IL-1), tumour necrosis factor-alpha (TNF-alpha) and IL-6. IL-1 and TNF-alpha are released first and stimulate the production and release of more cytokines, particularly IL-6.
Back to Wim Hof.
He took part in a fascinating case study published in 2012 in which he was subjected to three separate experiments. In the first experiment he was immersed in ice for more than an hour and his blood was exposed ex vivo (outside his body) to LPS (Lipopolysaccharide E Coli wall – this is used to create a standard inflammatory model in volunteers). In the second experiment the same tests were taken but he was not exposed to cold, and in the final experiment he was injected with the LPS. He used a concentration/meditation technique during all three experiments and was subjected to multiple blood testing to measure catecholamines, cortisol and cytokines. A variety of other data was collected including an illness severity score for the final experiment.
Notably, his cortisol increased following mediation but prior to cold exposure and his ex-vivo LPS stimulated blood showed a reduced production of pro- and anti-inflammatory cytokines after the cold exposure. These cytokine changes were still present in ex-vivo stored blood six days later! In the second experiment, only epinephrine levels increased following his meditation technique but there were no effects on cytokine production in the absence of a stressful stimulus. In the final experiment, his response was compared to that of 122 historical male LPS controls which had followed the same protocol using a variety of measurements of autonomic nervous system activity and innate immune response. Wim only reported a mild headache for ten minutes following LPS. This equals a symptom score of 1 whereas the mean symptom score of controls was 6.6 (2.8). He had a much greater increase in cortisol after LPS than the controls while his plasma catecholamine levels peaked after his concentration meditation technique and then dropped. Compared to controls he had a marked reduction in inflammatory cytokines following ice and endotoxin exposure. This was not seen in experiment 2 thus indicating the requirement for an external stimulus. It seemed that his concentration/meditation technique created a stress response which activates his SNS and HPA axis consequently releasing cortisol and catecholamines which are immunosuppressants. These finding are similar to that of the blood profile of volunteers during a bungee jumping experiment. This is contrary to conventional meditation techniques which reduce stress and catecholamine/cortisol levels.
Wim’s unique meditation technique involves cycles of hyperventilation followed by breath-holding and this might be responsible for the direct SNS activation and stress hormone effects i.e. he has exhibited the ability to consciously control his stress response leading to attenuation of his innate immune response.
The researchers questioned whether Wim was genetically gifted with unique superhuman abilities or whether this could be replicated in others.
They addressed their question in a follow-up experiment published in 2014 in which Wim taught his so-called Wim Hof method (meditation, cold exposure and the *breathing technique combination) to a group of 12 volunteers who were subsequently compared to 12 controls during exposure to endotoxin (similar to experiment 3 above). They received 4 days of intensive training in cold conditions in Poland and a further 2 to 3 hours/day of training back at home for 4 to 9 days leading into their endotoxin exposure.
*The breathing technique (2 exercises):
- Hyperventilate for 30 breaths
- Then exhale and hold breath as long as possible (2 to 3 minutes) – Retention Phase
- Breath retention is followed by a deep inhalation breath which is held for 10 seconds followed by a new breath cycle
- Deep inhalations and exhalations followed by breath holding for 10 seconds during which all body muscles are tightened.
This technique was used prior to and during the endotoxaemia experiment.
Control group physiology was unchanged during the experiment whereas the trained group immediately exhibited a profound acute respiratory alkalosis (pH 7.75) and adrenaline levels 3 fold greater than their baseline levels after using their breathing technique.
TNF-alpha, IL-6 and IL-8 were 53%, 57% and 51% lower respectively, while IL-10 was 194% greater in the trained group compared to the control group. There was a strong correlation between the increased adrenaline and IL-10 levels in the trained group and an inverse correlation between their pro- and anti-inflammatory cytokines. Adrenaline increases during endotoxaemia in controls but the peak adrenaline release in the trained group occurred 30 minutes after the breathing technique started and prior to the LPS administration.
The authors concluded that a short term training programme involving breathing techniques leads to adrenaline release which induces early IL-10 production resulting in attenuation of the pro-inflammatory innate immune response. The result is fewer symptoms and swifter normalisation of fever and cortisol levels.
Therefore using techniques which are rapidly and easily learnt the SNS can be activated resulting in voluntarily influencing of the vivo innate immune response. This could have important implications for a variety of medical conditions associated with persistent inflammation particularly autoimmune diseases.
Could it also have a role in reducing the inflammatory response that follows major surgery? Specifically could coaching in this technique pre-operatively, and in the anaesthetic room immediately prior to anaesthesia, and then continued as early as possible post-operatively at intervals, have any of the same effects given that it cannot be performed during surgery?
Given that breathing is free and at the very least would be an effective way to control anxiety pre-operatively, lead to very efficient pre-oxygenation prior to general anaesthesia and aid lung recruitment post-operatively it is certainly food for thought. Of course the challenge would be the resource for coaching the technique and the tight time scales within which to do it.
So far the Wim Hof Method is being embraced by the likes of Brian Mackenzie of Crossfit Endurance and the famed big wave surfer Laird Hamilton to name a few. They report huge benefits in their athletic performance and elite athletes are taking note.
Time will tell whether we can find cross fertilisation into the peri-operative sphere.
So go ahead and give Wim’s push up challenge a go – I managed 35 (felt similar to 15 usually) on the single breath hold and it felt bizarre – and post your thoughts and experiences.
Breathing and Stress Inoculation for Critical Decision Making Peri-operatively
“If you want to conquer the anxiety of life, live in the moment, live in the breath.” – Amit Ray
I’ve covered an area of breath control that may impact patient’s physiology peri-operatively but now for a different angle on breathing.
Time urgent clinical challenges may occur during emergency surgery and complicated elective surgery for both anaesthetists and surgeons. These can lead to acute physiological stress manifesting as an increase in heart rate with progressive degradation in critical decision-making and complex motor skills – see the diagrams below.
So, can breathe control be used to improve clinician performance?
Performance enhancing breathing is effective in reducing stress during of clinical challenge. This may lead to better critical decision-making and more accurate motor skill deployment thereby improving patient outcomes and long-term clinician health and performance.
The technique is called “Combat”, “Tactical” , “Autogenic”, “Square” or “Box” breathing. It was described in the book “On Combat: The Psychology and Physiology of Deadly Conflict in War and Peace” by Dave Grossman and is very simple to implement.
Take 3 to 5 breaths in the following fashion and visualise each number as you count. Start by inhaling to a count of 4, stop and hold your breath for a count of 4, then exhale to a count of 4, hold your breathe again to a count of 4 and keep repeating until you feel the calming effects. Or try this free app to guide you.
The great thing is that this can be done inconspicuously prior to starting a procedure and no one need know!
It may just lead to you making better decisions as well as experiencing less physiological stress in the process (beneficial for your long-term cardiovascular health)…
I look forward to your thoughts and comments…