Analgesia for Major Abdominal Surgery


This post serves as handout for my lecture of the above title I delivered at the Norwich Anaesthesia Update on the 8th December 2016.


As William Pollard said:

“Learning and innovation go hand in hand. The arrogance of success is to think that what you did yesterday will be sufficient for tomorrow.”

The two key components required to deliver successful ERAS are early mobilisation and early nutrition (assuming high quality surgery). Both of these are influenced directly by the anaesthetist’s fluid management and provision of effective analgesia.

Effective analgesia

The most effective analgesic option is not necessarily the option with the best pain relief efficacy but rather the one that allows optimal respiratory function and early mobilisation.


Attributes required:

  • Minimal adverse effects
    • no prolonged hypotension
    • no nausea and vomiting
    • no motor blockade
  • Easy to deploy at scale
  • High level of staff delivery compliance
  • Minimal attachments – portability
  • Cost-effective

Surgical Developments

Laparoscopic surgery

  • Open surgery involves a variety of approaches.
  • Rapid increase transverse approaches and the use of harmonic scalpels for open colorectal surgery – both reduce analgesic requirements.
  • Rapid increase laparoscopic approaches – now 48% of major colorectal and 50% increase over past 5 years (National Bowel Cancer Audit).
  • Robotic surgery increasing and moving from urological across to colorectal surgery.

These newer surgical approaches are game-changers for our analgesic strategies as they induce minimal somatic pain and we are mostly treating the visceral pain, which although intense initially, subsides within 12 to 24 hours.

Analgesic Developments

At the same time we have had a rapid expansion in our analgesic armamentarium. At the turn of the century either thoracic epidural analgesia or morphine PCA’s dominated. Since then, thanks to ultrasound, old techniques have been resurrected and existing techniques have found wider application.

Key primary techniques:

  • Thoracic Epidural Analgesia (TEA)
  • Spinal Opiate
  • Rectus Sheath Catheters (RSC)
  • Continuous Wound Infusion Catheters (CWIC)
  • Thoracic Paravertebral Blocks (TPVB)
  • Quadratus Lumborum Blocks (QLB)
  • TAP Blocks

I will not be discussing the final 3 techniques (TPVB, QLB or TAP Blocks) as although all of these have proven efficacy they either require experts, greater invasiveness or excessive complexity (to cover the entire abdomen with TAP blocks requires 4 injections & 2 catheters) hence not fulfilling my criteria of delivery at scale enabling easy standardisation. I will instead focus on the first four key techniques: TEA, Spinal Opiate, RSC & CWI along with non-opioid adjuvants, with a particular focus on Lidocaine Infusions.

Packages/Bundles of Analgesia:

Each primary technique needs to be delivered as an entire package or bundle of care with simple analgesia as the foundation and the addition of non-opioid adjuvants. We also find transdermal fentanyl patches a usual addition to our bundle.

Non-opioid Adjuvants:


  • Extensive evidence for opiate sparing properties & safety (1-5).
  • Cost-effective
  • All of our major surgery patients receive a pre-op dose (300mg) & 300mg in divided doses for 3 days post-op (modest dosaging for acute pain however older patients have experienced dizziness with larger doses in our experience) (6)


  1.  Mathiesen O, Møiniche S, Dahl JB. Gabapentin and postoperative pain: a qualitative and quantitative systematic review, with focus on procedure. BMC Anesthesiology. 2007;7(1):6–15.
  2.  Tiippana EM, Hamunen K, Kontinen VK, Kalso E. Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anesthesia & Analgesia. 2007 Jun;104(6):1545–56–tableofcontents.
  3. Efficacy of Pregabalin in Acute Postoperative Pain Under Different Surgical Categories: A Meta-Analysis. 2015 Nov;94(46):e1944.

  4. Arumugam S, Lau csm, Chamberlain RS. Use of preoperative gabapentin signi cantly reduces postoperative opioid consumption: a meta-analysis. Journal of Pain Research 2016:9 631–640

  5. Dauri M, Faria S, Gatti A, Celidonio L, Carpenedo R, Sabato AF. Gabapentin and Pregabalin for the Acute Post-operative Pain Management. A Systematic-narrative Review of the Recent Clinical Evidences. Current Drug Targets, 2009, 10, 716-733

  6. Perioperative gabapentinoids: choice of agent, dose, timing, and effects on chronic postsurgical pain. 2013 Nov;119(5):1215–21.


  • Extensive  evidence (1-3) for  efficacy via a variety of
    • routes,
    • timing (pre-, intra- & post-op),
    • boluses or infusions.
  • The simplest strategy = 0.5mg/kg bolus intra-operatively.
  • Reduction in inflammatory response is an additional benefit (4).
  • Animal models (5) suggest possible reduction in gut reperfusion injury which may be particularly useful following extended pneumoperitoneum.


  1. Perioperative ketamine for acute postoperative pain. 2006 Jan 25;(1):CD004603.

  2. Ketamine as adjuvant analgesic to opioids: a quantitative and qualitative systematic review. 2004 Aug;99(2):482–95.

  3. Intravenous sub-anesthetic ketamine for perioperative analgesia. 2016 Apr;32(2):160–7.

  4. Does intraoperative ketamine attenuate inflammatory reactivity following surgery? A systematic review and meta-analysis. 2012 Oct;115(4):934–43.

  5. Ketamine anesthesia reduces intestinal ischemia/reperfusion injury in rats. 2008 Sep 7;14(33):5192–6.

IV Lidocaine Infusions

See section following Spinal Opiate.

Fentanyl Patches

  • Very useful either for stepping down from epidurals or to provide visceral analgesia for the other primary techniques.
  • Eliminate the issue of non-compliance with drug administration where regularly prescribed analgesics as frequently treated as PRN drugs.
  • Limit the dosage to 12mcg patches for those over 70 years old &/or


  • Be aggressive.
  • Audits continue to report up to 60% of colorectal surgery patients experiencing PONV. This is a major obstacle to ERAS success.
  • Along with multimodal antie-emmetics intra-operatively  – cyclizine, ondansetron and dexamethazone.
  • Buccastem as a regular administration for 2 days of post-operative prophylaxis. Efficacious, cost-effectiveness & not reliant on gut function.

Primary Techniques

Thoracic Epidural Analgesia

  • Current gold standard although but this is under threat.
  • This Cochrane review (1)  is one of many demonstrating analgesic supremacy over morphine PCA & we all know nothing can beat the way a patient with a good epidural appears in theatre recovery.
  • That’s not the full story. Marret’s metanalysis (2) shows that this doesn’t translate into shorter hospital stays,
  • Nor does it lead to any survival advantage in updated meta-analysis (3) which includes the Peyton & Park studies that were powered for mortality.
  • And the beneficial effects of modulating the stress response appears to be short-lived in more recent studies (4) – glucose and cortisol rise were reduced in a epidural group compared to a morphine group at the end of surgery but no difference by 24 hours and no difference at all for cytokine response. Therefore unlikely to be of much clinical significance.
  • Epidural failure rates are a well known problem – quoted as 32% across a range of studies (5)
  • And attempts to keep them working incur significant healthcare worker time shown here by Tileul (6) comparing epidurals, PCAs & CWICs.
  • I won’t dwell on NAP-3 (7). As we know nerve injuries are rare but the bulk occur in peri-operative TEAs & of course most of the alternatives don’t have this risk at all.
  • I’m sure those of you who do POCU or critical care ward rounds also frequently encounter, as I do, the irritation of prolonged stays due to vasopressor dependency (roughly 20% of patients).
  • And even worse patients being drowned on the wards in attempts to manage the hypotension.


  • In this large ER cohort study (8) excessive fluid had the strongest association with morbidity it’s a really important issue.
  • Our decisions should be patient-centered but unfortunately patient experience is generally ignored in quantitative research. Our as yet unpublished nested qualitative study within our RCT comparing TEA to RSC (TERSC) (9) involved patents being interviewed in their homes a month after surgery regarding their experiences and acceptability of the techniques. Several TEA patients reported high levels of anxiety building up to the epidural as well as significant discomfort during insertion and feelings of claustrophobia.


  1. Patient controlled intravenous opioid analgesia versus continuous epidural analgesia for pain after intra-abdominal surgery. 2005 Jan 25;(1):CD004088
  2. Meta-analysis of epidural analgesia versus parenteral opioid analgesia after colorectal surgery. 2007 Jun;94(6):665–73.

  3. Neuraxial anesthesia for the prevention of postoperative mortality and major morbidity: an overview of cochrane systematic reviews. 2014 Sep;119(3):716–25.

  4. Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy. 2013 May;110(5):747–57.

  5. Failed epidural: causes and management. 2012 Aug;109(2):144–54.

  6. Cost-effectiveness analysis comparing epidural, patient-controlled intravenous morphine, and continuous wound infiltration for postoperative pain management after open abdominal surgery. 2012 Jun;108(6):998–1005.

  7. NAP3
  8. Adherence to the enhanced recovery after surgery protocol and outcomes after colorectal cancer surgery. 2011 May;146(5):571–7.

  9. Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial. 2014 Oct 21;15:400.

Spinal Opiate

  • Spinal opiate is a very attractive alternative. The skill set is inherent so it’s easy to deploy at scale. The rare but serious complications are less common than with epidurals (NAP3) and it’s single shot with no ongoing management requirements. The key indication is laparoscopic surgery or open surgery via transverse incisions.
  • Spinal morphine has shown efficacy over parenteral opiate for laparoscopic abdominal surgery. A Canadian study (1) randomized 50 patients to IT morphine + PRN oxycodone or morphine PCA and the intrathecal group had better pain control and less opiate consumption in the 1st 24 hrs, however 2 patients had excessive sedation and respiratory depression.
  • My personal experience is entirely with intrathecal diamorphine where we see these adverse events extremely rarely – we have experience of several thousand patients in this context (in fact morphine PCA has the highest incidence in our database).
  • Virlos et al (2) published a cohort study of 175 patients comparing spinal diamorphine to epidurals for laparoscopic colorectal surgery and not only did the spinal group have better pain relief but also shorter hospital stays & no adverse events despite using up to 1.5mg.
  • Subsequently the Royal Surrey (3) randomised 99 patients, in a practice-changing study, between epidurals, spinal diamorphine and morphine PCAs with all patients experiencing a robust ERP. Both spinal & epidural groups had better pain scores than the PCA group. However the epidural group fared worse than both the spinal and PCA groups when it came to the primary outcome measure of time to fitness for discharge – probably in part related to their slower return of bowel function. Spinals therefore gave the best of both worlds & for us is the technique of choice for laparoscopic colorectal surgery & in fact any laparoscopic major abdominal surgery.


  1. Spinal analgesia for laparoscopic colonic resection using an enhanced recovery after surgery programme: better analgesia, but no benefits on postoperative recovery: a randomized controlled trial. 2012 May;108(5):850–6.

  2. Short-term outcomes with intrathecal versus epidural analgesia in laparoscopic colorectal surgery. 2010 Sep;97(9):1401–6.

  3. Randomized clinical trial of epidural, spinal or patient-controlled analgesia for patients undergoing laparoscopic colorectal surgery. 2011 Aug;98(8):1068–78.

Lidocaine Infusions

  • Lidocaine infusions are a fascinating non-opioid adjuvant. I’ve been following this development for a few years but only recently introduced it into my own practice & I’m currently protocolising it locally.
  • There are multiple metanalyses (1-4) all demonstrating significant opiate sparing effects & also a reduction in N&V, ileus rates & hospital LOS following abdominal surgery. The gut effects are a direct effect on the gut smooth muscle in addition to the opiate sparing effects.
  • Specifically in the context of laparoscopic colorectal surgery this RCT (5) involving 64 patients randomized them between iv lidocaine or placebo with both groups receiving a fixed rate fentanyl infusion & PRN tramadol. The lidocaine group had better pain scores at rest & movement as well as a quicker return of bowel function & a shorter hospital stay.
  • Interestingly a Korean RCT (6) recruited gastrectomy patients & only infused lidocaine or placebo intra-operatively yet the analgesic advantage stretched out to 24 hrs along with a reduction in inflammatory response (CRP).
  • The dosage regimen from Ottawa Hospital of a 1-2mg/kg bolus followed by a 1-2mg/kg/hr infusion is very simple to implement and shown to be safe with extensive pharmacokinetic modelling. They have extensive experience over several years providing these infusions for several days post-op on general surgical wards.
  • A similar regimen has been adopted as part of the Scottish Laparoscopic Colorectal ERP.
  • I see this, & any other laparoscopic abdominal surgery, where spinal diamorphine is our technique of choice as it’s niche, whereas other surgical approaches involve techniques employing LA infusions therefore preventing use.


  1. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. 2008 Nov;95(11):1331–8.

  2. Impact of intravenous lidocaine infusion on postoperative analgesia and recovery from surgery: a systematic review of randomized controlled trials. 2010 Jun 18;70(9):1149–63.

  3. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. 2015 Jul 16;(7):CD009642.

  4. Efficacy and safety of intravenous lidocaine for postoperative analgesia and recovery after surgery: a systematic review with trial sequential analysis. 2016 Jun;116(6):770–83.

  5. Intravenous lidocaine for post-operative pain relief after hand-assisted laparoscopic colon surgery: a randomized, placebo-controlled clinical trial. 2014 Apr;18(4):373–80.

  6. Intraoperative systemic lidocaine for pre-emptive analgesics in subtotal gastrectomy: a prospective, randomized, double-blind, placebo-controlled study. 2014 Jun;57(3):175–82.

Rectus Sheath Catheters (RSC)

  • This is truly resurgence of a forgotten technique, which was originally described by Carl Ludwig Schleich in 1899, & was used to provide abdominal wall relaxation until the emergence of muscle relaxants, thus preceding epidural analgesia by many decades.
  • As you can see in this video LA is injected in the space between the rectus muscle & the posterior rectus sheath and this provides sensory dermatomal blockade of the entire abdominal wall.
  • The catheters can either be placed surgically at the end, which work, but observational data suggest not quite as well as Ultrasound guided insertion pre-op. Possible reasons include the benefit of pre-emptive analgesia, LA leakage when surgically placed if space dissected open, the surgical technique may result in placement in the space between peritoneum & sheath rather than muscle & sheath.
  • We use very small accurate portable pumps carried in sling bags over patient’s shoulders together with bags of 0.2% ropivacaine. We set the pump to deliver a 40ml bolus 4 hourly equally to both catheters via a Y-connector. Staff or patient can press the delivery button & the bolus is then delivered over 24 minutes with a 4 hour lock-out in place. Anecdotally I found inferior results when using the same dosage but delivered as continuous infusions which is likely due to a bolus needed to burst the space open and achieve a nerve block whilst the LA likely just remains at the end of the catheter during a slow continuous infusion.
  • A cohort study from Devon (1) using US guided RSC showed similar pain relief to epidurals for open colorectal surgery but less hypotension.
  • And another cohort study from Somerset (2) comparing surgically placed RSC to epidurals reported equivalent analgesia but faster recovery.
  • In a series of 200 consecutive RSC (3) for major urological surgery consistently low pain score & low morphine consumption were reported.
  • An Egyptian RCT (4) of 60 open midline colorectal patients compared RSC to CWIC & found significantly better pain relief, less rescue analgesia & less morphine consumption in favour of RSC. This is very relevant to the next section.
  • To date their have been a lack of RCT comparing RSC to epdurals. Exeter have completed one with over 80 patients but not yet reported to my knowledge & we will soon be completing our TERSC study (5) of 132 patients in January 2017 with reporting to follow later in 2017.


  1. Ultrasonography guided rectus sheath catheters versus epidural analgesia for open colorectal cancer surgery in a single centre. 2013 Nov;95(8):591–4.

  2. Rectus sheath catheters provide equivalent analgesia to epidurals following laparotomy for colorectal surgery. 2015 Oct;97(7):530–3.

  3. Use of rectus sheath catheters for pain relief in patients undergoing major pelvic urological surgery. 2014 Feb;113(2):246–53.

  4. Postoperative analgesia of ultrasound guided rectus sheath catheters versus continuous wound catheters for colorectal surgery: A randomized clinical trial. Egypt J Anaesth (2016),
  5. Thoracic Epidural analgesia versus Rectus Sheath Catheters for open midline incisions in major abdominal surgery within an enhanced recovery programme (TERSC): study protocol for a randomised controlled trial. 2014 Oct 21;15:400.

Continuous Wound Infusion (CWI)

  • The 1st reports of LA wound infusion via polythene tubes go back to the 50’s, with RCT’s appearing in the 80’s, elastomeric pumps in the 90’s and better designed trials appearing since the millennium.
  • Advantages
    • Simplicity of placement & management.
    • Can be used for any sort of incision, providing the surgeon places the catheter in the correct tissue plane i.e. pre-peritoneal rather than inter-muscular.
  • Disadvantages
    • Potentially needing more than 1 pump for certain incisions.
    • Usually need a morphine PCA as well so an additional pump to complicate mobilisation.
    • Only the wound is anaesthetized, as opposed to abdominal wall blocks which provide wider coverage thereby analgesing drains & stomas as well.
    • This in turn leads to higher iv opiate requirement in the 1st 24 hrs, compared to say RSC, as we saw e.g. earlier Egyptian study.
    • Cost with these roughly double the price of a RSC kit.
  • Modern CWIC are multi-holed wound soaker catheters which come in different lengths to choose according to wound length. These guarantee even distribution of LA throughout the length of the catheter & wound. The most common regimen is to inject a 10ml bolus of 0.2% ropivacaine down the catheter following by 10mls/hr via a small portable pump (we use the same device as for RSC) or elastomeric devices.
  • There have been plenty of proof of concept studies for midline incisions but these 2 recent RCTs compared CWI to TEA for open colorectal surgery with midline incisions. They reported contrasting results with the Italian study (1) in favour of CWI & the Canadian study (2) in favour of TEA however the methodology was quite different. Both used the standard CWIC regimen above. However the Italian study compared to a suboptimal fixed rate epidural at 10mls/hr using plain ropivacaine & a morphine PCA for breakthrough while the Canadian study compared to an optimised PCEA using a bupivacaine/fentanyl mixture. Clearly very different comparisons. My personal bias combining the Egyptian study, these 2 studies, the disadvantages above & my own experience is to favour RSC over CWIC for midline incisions.
  • My practice to date has been to reserve CWIC for rescue when laparoscopic liver resections are converted to open or epidural placement fails or is contra-indicated/refused. Following very favourable results I am considering moving this to my primary technique.
  • And it turns out this is a burgeoning area of research with 3 recent relevant RCT. The 1st RCT from Edinburgh (3) compared CWI to TEA for open liver resections. 65 patients were randomised and blinded to their group allocation. Although the epidural group had lower pain scores, when it came to the primary outcome of hospital length of stay, this was significantly better in the CWI group illustrating the point that effective analgesia wins over perfectly efficacious analgesia. This was despite a greater number of major resections and longer operating time in the CWI group.
  • The 2nd study is also from Edinburgh (4). This time unblinded with 49 recruited to TAP block followed by CWI & 44 to TEA. Again pain scores were similar but interestingly the TEA group required more opiate after day 1 & the primary outcome of fitness to D/C from hospital was significantly in favour of CWI again. This was in part due to significantly greater time on HDU due to vasopressor dependency in 20% of TEA patients. There was no difference in inflammatory response or haemodynamic responses during surgery.
  • And finally we have a recent Dutch study (5) from 2 centres which included open liver and pancreatic surgery. It was an unblinded non-inferiority comparison of a composite outcome combining pain scores, opiate side effects & patient satisfaction. 55 & 47 patients were analysed in CWI & TEA groups respectively & non-inferiority was established. Again they reported a greater need for vasopressors intra- & post-operatively.


  1. The postoperative analgesic efficacy of preperitoneal continuous wound infusion compared to epidural continuous infusion with local anesthetics after colorectal cancer surgery: a randomized controlled multicenter study. 2012 Dec;115(6):1442–50.

  2. Epidural versus continuous preperitoneal analgesia during fast-track open colorectal surgery: a randomized controlled trial. 2013 Mar;118(3):622–30.

  3. Randomized clinical trial of local infiltration plus patient-controlled opiate analgesia vs. epidural analgesia following liver resection surgery. 2012 Sep;14(9):611–8.

  4. Randomized clinical trial of perioperative nerve block and continuous local anaesthetic infiltration via wound catheter versus epidural analgesia in open liver resection (LIVER 2 trial). 2015 Dec;102(13):1619–28.


  • Spinal diamorphine possibly combined with IV Lidocaine infusion for major laparoscopic abdominal surgery, open transverse incisions and robotics.
  • Consider RSC for open midline surgery,
  • CWI for other incisions  – in particular open liver surgery.
  • Thoracic Epidurals still have an important role but I think in the future they will be used more selectively e.g. complicated abdomens, young inflammatory bowel disease patients, anorectal surgery (particularly ELAPSE) and chronic pain patients.
  • Maximally use anti-emmetics, simple analgesia & non-opioid adjuvants (gabapentin & ketamine) in a standardised fashion & consider transdermal fentanyl patches to control visceral pain & to aid step down from epidurals.

Take Home Message

Choose the most effective form of analgesia to meet the requirements of the patient & the surgical approach. This is not always the option with the best pain scores.

As George Bernard Shaw said:

“Progress is impossible without change, and those who cannot change their minds cannot change anything.”


Developing an idea into an RCT: TERSC

Context: This post is the content of a lecture I delivered to Specialist Trainee Doctors  in Anaesthesia from the North West of England at the NWRAG (North West Research and Audit Group) QI & Research Day on the 24th October 2016.


I want you to ask yourself – could I do an experimental clinical study?

In this post I use my current RCT, the TERSC study, as a case study for discussing various concepts related to developing ideas into trials. For full details about the TERSC study have a look at our protocol published in the TRIALS journal.

Simon Sinek’s TED talk “How great leaders inspire action.” which followed from his book “Start with Why” is worth a watch – it’s had over 28 million views.

In it he explains the simple concept of the “Golden Circle”. It goes like this: Most organizations work from the outside in, that is they tell you what they do, some know how they do it and very few know why they do it. Great organisations work from the inside out – they know their why first. He uses Apple as an example saying if they were like other computer companies they would say: “We make great computers, they’re beautifully designed and easy to use. Want to buy one?”. Instead they say: “Everything we do we believe in challenging the status quo. We believe in thinking differently. The way we challenge the status quo is by making our products beautifully designed, simple to use and user-friendly. We just happen to make great computers. Want to buy one?”

When I reflected on this concept I realized the Golden Circle could also apply to how we develop and deliver research studies.


Let’s start with “Why”. What fascinates you? What makes you curious? Have you ever had an academic itch to scratch? Something you needed to know, a burning curiosity? That could be your “why”. Of course your “why” may simply be getting something published and enhancing your CV. This is perfectly acceptable but without a stronger “why” you may struggle to push through the tough bits.

I suggest exploring what your clinical purposes and passions are for your career, and develop your research around those – they will form your “why”. Mine over the years have been a focus on introducing system-wide changes in the clinical areas which I believed would have the largest impact on patient outcomes e.g. sepsis care bundles in 2005, hospital track and trigger system redesign, low tidal volume ventilation on ICU, health care associated infection care bundles in 2005 and enhanced recovery programmes for all major surgery since 2008 to name a few. More recently, aside from my own research, it has been to increase my organisation’s overall research output as the Director of R&D.

In 2013 I heard a colleague from Exeter talk about his experience with an intervention called Rectus Sheath Catheters (RSC). RSC’s provide analgesia for major abdominal surgery with an open midline approach and their data suggested it was potentially a reasonable alternative to thoracic epidural analgesia (TEA). I contacted him for details about insertion and management of these and proceeded to introduce them into my practice. Very soon it was clear to me that this was an effective technique e.g. when I went to visit one of my patients, called David, on the ward the morning after his major abdominal operation I found that he’d already eaten his breakfast and had been walking around the ward! In fact he required another similar abdominal operation a month later and requested me to insert the RSC again and we had the same great results. Despite this there seemed to be very poor uptake of RSC.

Indeed there is a marked clinical variation in analgesic techniques for major abdominal surgery within departments, within regions, and nationally, with seemingly earlier adoption of various abdominal wall block procedures in the South of England compared to the North. This sort of clinical variation within a region was measured in the South West by the SWARM trainee research network in a survey of practice. As there were no RCT comparing RSC to TEA this became my “why” for the TERSC study.

More recently my inspiration for possible perioperative innovations and research projects have stemmed from my various hobby interests:

  • Sports medicine e.g. a current RCT to compare Superstarch to standard PreLoad pre-operatively to reduce insulin resistance and consequently morbidity,
  • Biohacking e.g. use of HRV to predict deterioration postoperatively and Wim Hof breathing techniques to reduce immune activation and consequent inflammation peri-operatively
  • Nutritional science e.g. reduction in fatty liver pre-liver resection surgery using LCHF diets and reduction in inflammation with the same.

Part of your “why” will include the awareness of the wider benefits to you, other staff, the patient and your organisation of being involved in research.

Here are some of the benefits generic to all clinical research activity and some specifically to the TERSC study example:

  • Improved patient outcomes regardless of group allocation
  • Improved hospital outcomes for hospitals that are more research active
  • Attract higher calibre staff in the future
  • Research experience
  • Chief Investigator (CI) experience
  • Project management experience
  • Create a research culture
  • Create structures for perioperative research delivery
  • RSC training
  • RSC packs
  • Departmental profile
  • Lecture invitations
  • Research Grants and funding
  • Academic collaborators
  • Peer review invitations
  • Trial Steering Committee invitation
  • Appreciate value of mixed methods research
  • Value of Patient and Public Involvement (PPI) and their potential as focus groups for other projects
  • NIHR Portfolio accrual benefitting other roles.

So work out your “Why” – this will give you inspiration for your research ideas and maintain your enthusiasm.


Focus, discipline & resilience are prerequisites to push through the inevitable bumps, but make sure you also think about strategy and tactics to ensure you succeed without blowing up along the way like Johnny here. Of course the actual moral of that video is that if you give a South African half an opportunity he’ll take it!

To do this you need to identify your strength & weakness e.g. having a vision and project management are my strengths but I know I’m weaker at statistics and I don’t enjoy the reporting aspect – some of these I’ll work on e.g. practice my academic writing skills, but others e.g. acquiring high level statistical skills are not worth the time consumption when I have access to statisticians.

Develop your leadership skills and be able to delegate effectively. This requires serious investment in your teams. Collaborate and surround yourself with experts – some of them will become mentors. Volunteer to be the local Principal Investigator (PI) for some large multicentre studies. Not only will this be an extremely educational experience regarding how such large studies are designed, protocols written and delivered, but will connect you with the CI’s of these studies who may become one of those collaborators (as has been the case with TERSC). Attend relevant national research meetings where you will be able to network gaining further collaborators and mentors. In my experience our academics are all very approachable and helpful. The key meetings are the UK Critical Care Research Forum & the Peri-operative Medicine Clinical Trials Network conferences which include sections where you can present your study idea and get feedback from the experts. I would encourage registering with the latter organisation as a PI or Local Investigator (LI) to receive some training and put you in position to be offered a PI role for one of the large studies.

Get some research education. There are several good Research Methodology courses available. There is a comprehensive generic 5 day course provided by the combined universities of the North West which takes place twice a year (April & September). Single days can also be attended. The 2 day Edinburgh course is specifically aimed at anaesthesia and critical care research and held every November.

Learn how to tackle the approvals process and understand the HRA system. This will save you a lot of frustration in the future. You will need to register on IRAS and work through the on-line tutorials to get permission to undertake any research. The key is a well written detailed protocol which you can paste into many of the domains.

Try to develop research that aligns with your consultant job plan as much as possible to make it more manageable. My job plan as an example has evolved over a 10 year period whereby the clinical components consist of a CPET clinic, critical care and core anaesthesia lists of major colorectal and hepatobiliary surgery. This aligns perfectly with my research topics and my leadership of the Enhanced Recovery Programmes. I am able to see some of my research patients in the clinic and help enroll them into trials, subsequently anaesthetise them and also follow them up on my critical care days. I do a session as Specialty Lead for Anaesthesia for the NIHR GM CRN and another session as R&D Director for my Trust. Both of these research managerial roles are synergistic with my personal research in a variety of ways.

Balance is something I’ve got wrong in the past so I’ve worked hard at applying the Pareto principle i.e. 20% of your invested input is responsible for 80% of the results obtained. The key is identifying the 80% of your time which is gaining you very little output and ruthlessly eliminating it. That means strategically saying no to some requests.

Spend time developing systems and structures up front that will maximize your future efficiency e.g. I use these standardised templates for all my study protocols, outcome measures and reporting. Use all the help you can get for study design and advice on funding options and possible grant applications. The NIHR North West Research Design Service (RDS) provide this for free including connecting you with appropriate academics to be co-applicants.

I use a variety of productivity tools to streamline my workload e.g. Inbox zero; E-mail batching with delayed sending (for Mac mail client users); Rescue Time; Evernote (this is a game changer with wide application); Dropbox (allows easy collaboration, co-authoring and document sharing) and work off-line while using the Pomodora technique for Deep Work.

If you implement these tips together with any you discover you’ll maximise efficiency but as the great Peter Drucker said:

“Efficiency is doing things right; effectiveness is doing the right things.”

In other words only apply your effort and efficiency to tasks you’ve identified via the Pareto Principle as generating you the most output. This will make you maximally effective.

Ultimately getting your “How” right will allow you to spin multiple professional plates while not neglecting time for family, fun and staying as fit and healthy as possible – this is the pathway to long-term success.


The “What” for me is the methodology of the specific study and the lessons you learn during the delivery. We learn more from our mistakes than our successes so I’ve learnt plenty from each of my studies. Probably the main one for TERSC is not to do another complex intervention analgesic study!

Start with defining the objective of the study. The aim of this study was to assess the efficacy, safety and acceptability to patients of RSC.

The acceptability was measured using a nested qualitative study which is quite novel in anaesthesia research. It will give a balance between the traditional quantitative outcomes and the patients’ views – which is ultimately what we should base our choices on.

We included two sub-studies which measure the plasma concentration of the local anaesthetic agents and markers of stress response in the same 20 patients. We used convenience sampling (in order to avoid blood sampling out of hours) to recruit these patients but ensured a balance from each study group and between types of surgery.

The framework of this study  is a randomised parallel group concealed allocation non-blinded superiority trial with a nested qualitative study of a subset of patients. As the study involves two active comparators we would only need to demonstrate non-inferiority due to some of the other advantages of the new intervention however this would require a much larger which would not be feasible to recruit to from a single centre – see “lessons learnt” section below.

Our study population are adult patients undergoing open midline major abdominal surgery who are willing to consent. We exclude those with allergies or contra-indications to the interventions, other incisions, chronic abdominal pain, opiate tolerance and ano-rectal surgery.

The interventions were a standard TEA and RSC. Importantly we are comparing an optimal TEA to an optimal RSC. Here is a link to a video I produced of a RSC intervention on a patient with a BMI of 40. Note that this study is not merely about the comparison between these two primary analgesic techniques but rather a comparison of two entire complex analgesic packages and that both groups experience an optimal enhanced recovery pathway.

The primary outcome was the difference in mean pain score (VAS) on movement from supine to sitting position at 24 hours after extubation between groups. I chose this as it is a key marker of the ability to mobilise early and has been used in other similar studies.

Secondary outcomes include:

  • Further comparisons of analgesic efficacy and effectiveness e.g. VAS at other time points & the evolution thereof, time to 1st opiate & total opiate, sleep quality VAS, categorisation of functional quality of analgesia i.e. mobility and breathing & an overall satisfaction score of analgesia;
  • Functional recovery comparing PQRS scores from baseline, time to mobilisation, return of GI function; achievement of ERP mobilisation goals, time to meeting discharge criteria and hospital length of stay;
  • Safety & morbidity are measured by fluid balance, incidence of hypotension, nausea & vomiting VAS, incidence of ileus and a day 5 POMS with any surgical complications within 30 days classified for severity according to the Clavien-Dindo scale.
  • Only short-term cost-effectiveness will be calculated limited to assessing procedural costs (equipment and time) and length of stay in critical care and ward beds.

Sample size was calculated as 60 patients per arm based on achieving 85% power to detect a 10 mm difference in the primary end point, from 40 mm in the TEA group to 30mm (SD=18mm) in the RSC group, at the 5% level (two-sided t-test). A 10mm change has been reported previously as the minimum VAS change that was clinically significant (MCID). The mean and standard deviation for the TEA group was taken from large metanalyses. There is no published RSC RCT data on which to base a mean VAS thus we have postulated a MCID improvement in mean VAS. As these are both active interventions there is unlikely to be any difference in the efficacy (for working interventions) but we are assuming there will be lower failure rates for RSC  (6% has been reported in a large observational series whereas TEA failure rates of 30-40% are reported in the literature) which may influence the primary outcomes via the intention to treat analysis.

We are utilising multimodal approaches to recruit patients. Research nurses attend Cancer MDT for awareness of any eligible cases and attendance dates. This also embeds them in clinical teams raising culture and awareness. Pre-operative clinics are attended. Patient and clinical specific TERSC posters are in all clinics. The Waiting List Clerks are regularly contacted to search for cases and the theatreman system is interrogated twice a week for any missing cases. All surgeons and anaesthetists who do pre-operative clinics are aware of eligibility criteria. I produce a recruitment certificate for clinicians whose patients have been recruited to use for their appraisal folders. And the list goes on…

I spent substantial time working with the team at Imperial College CTU to design the TERSC study specifics for their online InForm database system. This performs the randomisation function providing allocation concealment. Our allocation sequence generation uses 3 surgical strata & 2 age strata as these groups would have expected differences in the secondary outcomes and need to be balanced between the groups.

Data collection and management also make use of this online system with source data from information collected in theatre, patient diaries, PQRS questionnaires and case notes. It also provides on-going governance and is auditable regarding any data changes or manipulation ensuring this study conforms to the highest levels of research quality.

Lessons learnt:

  • Difficulty in recruitment prediction at trial design due to evolving surgical approaches (open cases are increasingly transverse incisions rather than midline & retiring open surgeons have been replaced by laparoscopic surgeons).
  • Impossible to model the impact of opiate tolerance, chronic abdominal pain & midline scarring on rrecruitment.
  • Superiority versus Non-inferiority. Using superiority is a gamble as very difficult to show a difference between 2 active comparators. Non-inferiority would be ideal as a RSC only needs to be no worse than TEA on the primary outcome however the sample size is not achievable in a single centre and this complex intervention was not feasible to conduct in multiple centres at the time it was designed. Hence the superiority approach was a pragmatic choice and as the reported rate of epidural failure from larger studies is much higher than the rates reported from observational series for RSC it was considered reasonable. All the secondary outcomes together with the patient acceptability data from the qualitative study will help to interpret the results.
  • A functional primary outcome e.g. length of hospital stay would have been more relevant to me however it would have required a much larger sample size to show even a 1 day reduction due to the already short stays for colonic surgery.
  • The resource intensity of recruitment across clinics – I was naive to the geographically spread of the clinics these patients attend. This realisation has informed other current and future perioperative studies.
  • The workload involved in delivering the RSC intervention with limited practitioners – two colleagues who were proficient during the design phase were not available during delivery (one emigrated and the other on maternity leave). The vast majority of RSC were inserted by me & one other colleague. I had hoped to train other colleagues during the study but the number of RSC available to train each individual to the level necessary for study patients has been insufficient. This is due to the large number of different anaesthetists covering all of these lists and half the potential RSC training cases being randomised to TEA. Training will be easier after the study concludes.
  • Training of recovery and ward staff in managing the RSC and delivering the LA boluses on time via the AmBit pumps has been challenging, particularly as the colorectal ward was changed during the study. This led to many new nurses to train. The use of bank staff on night staff also resulted in some RSC patients not receiving boluses. This issue has led to some patients with RSC losing faith in the intervention when they perceive staff lack of confidence in using the pumps which is likely to affect their analgesic experience due to the psychological component (the qualitative study has highlighted this).
  • In view of the difficulty of training staff to deliver the RSC boluses on time via the pump that continuous infusions may have been a better option. I had decided on boluses over continuous due to my clinical experience, & that of others, with both options prior to the study however it has not turned out to be pragmatic and has also introduced the other variable that the RSC pain score will be influenced by the proximity to a bolus whilst the epidural is not.
  • In practice the incredible subjectivity of VAS as an end point is concerning. It is well validated and used for similar studies but seems so dependent on each patients’ frame of reference. In future I would consider instead one of the composite scores e.g. OBAS if a functional primary outcome wasn’t feasible from a recruitment point of view.
  • Rather than selecting a single VAS pain score time point for the primary outcome I would rather perform time point averaging over all 6 time points. This would smooth out the influence of the timing of RSC boluses and any missing data and be more representative of the entire time course of both interventions. We will be reporting this as a secondary measurement.
  • The resource intensity of data collection – the fixed time points for VAS scoring allows little flexibility and frequent late operation finishes has led to very difficult time points for data collection. For future studies I would sacrifice scientific accuracy for pragmatism and collect pain data twice a day without being specific on times. This would allow our Acute Pain Teams to contribute to some of this data collection for the research teams during their routine rounds.

In the ideal world I would have conducted a feasibility or a pilot study to tease out most of these issues. However the NIHR grant I was awarded had put out a themed call for surgical studies that year giving me my best chance of success with the application. These grants are incredibly competitive with far lower probability I would have received the award by delaying the application in order to perform a feasibility study. Ultimately a necessary tactical decision. In addition a feasibility study of this nature would still have required a research nurse to deliver it. These are not available without NIHR portfolio status and funding. A chicken and egg scenario.

In summary:

First identify your “Why”, then develop your “How”  (your generic structure improved over time) & finally your “What”  (how you actually deliver a specific project).

Keep the design as simple & pragmatic as possible to increase the likelihood of completion.

Using the TERSC study for illustration probably hasn’t enthused you to do your own study, so instead I offer two further examples of studies I’ve completed which would have been feasible for any of you.

The first was an RCT which compared 3 different sedation techniques for ERCP. I completed this while I was a specialist registrar back in 2002. I recruited, consented, delivered the intervention and collected all the data during my allocated research day. I understand the current training programme in anaesthesia still allows a research day if a study of sufficient quality is undertaken.

Another was a prospective haemodynamic study I managed to deliver entirely during my clinical sessions on ICU as a consultant without any help apart from a few of the research nurses pitching in towards the end.

These demonstrate that clinical research is feasible within a conventional clinical training  programme and consultant job. Models for non-academic research career pathways are being keenly looked at by the NIHR Anaesthesia National Specialty Group and the NIAA. The Association of UK University Hospitals have also produced a useful document regarding SPA/PA allocation which can be used for annual job planning allocation.

So, you CAN all do an experimental clinical study!

I would love some feedback in the comments section…

Could the simple power of breathing influence surgical outcomes?

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…

Blue Sky Ideas for Perioperative Care – An Introduction

Exciting changes are afoot in medicine. Twenty-first-century medicine has aspirations to deliver so-called Precision, Personalised or Stratified Medicine where diagnostics and therapeutics are tailored to individual genomics, molecular analysis and phenotypes. Individuals have been using a similar approach to optimise their personal health and performance using the concept of “Biohacking”, “self-optimisation” and the “Quantified self”. This paradigm has gained traction in the United States over recent years and the UK is set to follow. The concept is that of using yourself as an “N of one experiment”  to continuously test various nutritional approaches, supplements, biotechnology and forms of exercise.


At the same time Functional or Integrative medicine has been evolving over the past twenty years in the US and is now becoming mainstream. Several “Ivy League” institutions have begun providing functional medicine alongside more traditional specialties. The traditional medical model focuses on disease diagnosis by “single organ system” doctors who then provide symptomatic treatment. This is a disease-centred model. Functional medicine focuses on the cause of disease using a system-wide biological approach and a patient-centred model.

Furthermore, innovations developed to enhance athletic performance in the realm of sports medicine research may application in the clinical population.

Professionally I have been immersed in the acute medical specialities of anaesthesia and intensive care medicine for over twenty years, driving perioperative innovations via Enhanced Recovery Programmes for the past 8 years and consumed with research delivery and management for the past seven years.

On a personal level, I’ve pursued endurance sport for most of my life, starting with my first marathon in 1990 and triathlon for over 20 years. I have been optimising my own health and performance using biohacking principles for the past two and a half years. This has been a revelation. My family and some friends have experienced great improvements in health and performance after implementing my nutritional changes.

I believe some of these concepts have the potential to cross fertilise into clinical areas. This blog will focus on the possible translation of my various discoveries combining my area of expertise – perioperative care for major surgery – with my hobby interests of enhancing human performance. Many of the concepts will be considered “blue sky” thinking in traditional clinical medicine and may not be feasible to test with conventional research trials. This does not demean their potential value to patients and society more widely.


I will challenge dogmas, suggest new paradigms, stimulate debate and hopefully introduce some controversy.

Each of my future posts will explore a concept I encounter as I attempt further self-optimisation and through my broader research of these developing fields.

I hope I have sparked your interest for future posts focusing on a different “blue sky idea” each month.

Insulin Resistance & Complications after Major Surgery – Can they be Ameliorated?

The development of insulin resistance and hyperglycaemia following surgery is a well-documented phenomenon which is associated with increased morbidity and mortality.1–3 Insulin sensitivity is reduced by approximately 50% following elective surgery and persists for at least five days postoperatively in the case of upper abdominal surgery. There is a dose-response relationship between the magnitude of surgery and the degree of insulin resistance postoperatively. In the case of colorectal surgery where the magnitude is variable, the change is closely correlated with the duration of surgery. Blood loss is the other independent predictor of the degree of insulin resistance. Therefore, this metabolic variable is governed by the degree of surgical trauma itself rather than any predisposing or associated factors.

It appears that in the postoperative context endogenous glucose production (EGP) in the liver is unaffected by the suppressive effect of insulin per se. Therefore, the changes in insulin sensitivity following surgery are secondary to alterations in peripheral glucose uptake alone. We may reasonably assume that as skeletal muscle is the largest organ involved it is the main metabolic site.

The precise mechanism behind this loss of insulin sensitivity is unknown but it has been demonstrated that providing carbohydrates pre-operatively can attenuate this effect.4–6 Pre-operative carbohydrate drinks were also found to reduce pre-operative anxiety and hunger.7 There is also evidence that pre-operative carbohydrate drinks may decrease post-operative muscle mass loss and function and attenuates protein catabolism. 6,8–11

In addition, receiving a carbohydrate drink two hours before the start of anaesthesia does not significantly affect the gastric residual volume compared to patients fasted overnight.2,4,7,12

This practice, in conjunction with several other interventions, has now become routine with the introduction of Enhanced Recovery Protocols (ERP). These have been shown to reduce length of stay and complication rates for major surgery.13-16 A recent ERAS cohort study showed that patients that were treated with preoperative carbohydrates, experienced a 44% reduction in the risk of postoperative symptoms.17

In the search for a treatment for the rare group of inherited, metabolic disorders known as Glycogen Storage Diseases (GSD), a hydrothermally processed maize starch (HPMS) was developed with the aim of providing overnight blood glucose stability with a lower glycaemic index (GI).18 Two small trials led to the development of a high-amylopectin-containing cornstarch. This compound demonstrated a longer duration of action and a lower initial increase in blood glucose with lower peak concentration compared to standard uncooked cornstarch. 18,19

Hydrothermally processed maize starches, or so-called Superstarch, have recently been used as an alternative to standard, maltodextrin (MAL) based drinks within sports nutrition. They are used to provide stable blood glucose concentrations over time and avoid a spike in insulin concentration, factors which are thought to be advantageous in endurance exercise. This was investigated in a comparison of SuperStarch to a standard MAL formulation in a randomized, controlled crossover trial in nine elite cyclists.19 These participants’ ingested 1mg/kg of either MAL or HPMS, rested for 30 minutes, exercised for 150 min at 70% peak VO2 and then at 100% peak VO2 until they fatigued. Following exercise another 1mg/kg of HPMS or MAL was taken and the participants then rested for 90 min. The researchers found that during exercise and recovery HPMS provided more stable blood glucose levels, blunted insulin release and increased levels of fatty acids and glycerol, suggesting increased lipolysis. There was also a reduced initial spike in blood glucose and insulin following ingestion of HPMS compared to MAL. Thus despite consuming a product manufactured from carbohydrate it seems to behave like a fat in the body and effectively maintains fat metabolism. This would translate into preservation of insulin sensitivity, the favourable inverse of insulin resistance.

A major concern regarding the administration of drinks to patients within 2 hours of induction of general anaesthesia is the risk of pulmonary aspiration secondary to regurgitation of gastric contents. Gastric emptying is influenced by carbohydrate load and by osmolality, with increasing osmolality associated with prolongation of gastric emptying.2,12,21-24 Therefore, it stands that increasing the complexity of the carbohydrate source would increase speed of gastric emptying whilst providing the same calorific content. Indeed this is the case, with maltodextrin based carbohydrate drinks currently given pre-operatively as part of ERP having little effect on gastric residual volume at the start of anaesthesia, and actually result in less residual volume than a starved state. 4,7,12

Preload®, the pre-operative carbohydrate drink used in ERP across the NHS and in our institution, has an osmolality of 135mOsm/kg when mixed in the standard dilution (one 50g sachet is diluted with 400ml water). Generation UCAN is a powder-based sports energy drink mix, which makes use of SuperStarch, which has an osmolality of 89mOsm/kg when 60g, is diluted into 500ml water. This indicates that Generation UCAN will be emptied from the stomach more rapidly than Preload®.

The rationale for this proof of concept study is that HPMS drinks given pre-operatively may result in a greater reduction in insulin resistance post-operatively than the standard maltodextrin containing carbohydrate drinks due to a longer duration of action, a greater reduction in peak glucose concentration, a greater reduction in post-operative blood insulin levels and a greater lipid oxidation. This in turn may lead to a greater reduction in muscle loss and morbidity, specifically infectious complications, and in turn time to fitness for hospital discharge.

The initial proof of concept study will primarily measure chnages in insulin resitance using the HOMA technique 25,26 which mathematically derives insulin sesnsitivity from paired blood glucose and insulin results. These will be obtained from each patient in a fasted state pre-operatively and then on each of the first 3 mornings post-operatively. Other relevant outcomes e.g. changes in daily hand grip strength, safety regarding gastric emptying (we will employ ultrasound measurement of gastric volumes prior to anaesthesia 27-29) and hospital length of stay will be compared.

If a physiological proof of concept is demonstrated then a subsequent study will be powered to show a clincally significant diffference in hsopital length of stay.

We look forward to delivering this study and gaining a further understanding of this intersting area of pathophysiology.

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  28. Bouvet L et al. Clinical Assessment of the Ultrasonographic Measurement of Antral Area for Estimating Preoperative Gastric Content and Volume. Anesthesiology 114, 1086–92 (2011).
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Pain relief after colonic surgery. Has the epidural had it’s day?

Dr Anton Krige

Epidural analgesia (EA) grew in popularity through the nineties with several studies and systematic reviews [1,2] reporting superior analgesic efficacy compared to high dose opiate. A systematic review followed suggesting EA reduced morbidity following major abdominal surgery [3] and a Cochrane Review [4] demonstrated a reduction in GI paralysis.

In recent years Enhanced Recovery Programs (ERP) have become widely established in the UK, with early mobilisation a key component. Effective pain relief is obviously pivotal to achieving early mobilisation, and EA remains the recommended technique in the ERAS Society guidelines for colonic and rectal surgery [5,6], as well as in the latest NHS ERP generic pathway [7], both published in 2012.

However a gradual paradigm shift away from EA is taking place both internationally, largely in Australasia, as well as in the UK.

There are a variety of factors contributing to this change in clinical practice.

The first was the publication over 10 years ago now of the MASTERS Trial [8], which with 915 patients recruited remains the largest RCT investigating EA for abdominal surgery. This multi-centre trial across Australasia & SE Asia was designed to determine if EA reduced mortality and major morbidity in high-risk major abdominal surgery. It failed to do so, and mortality was in fact non-significantly higher in the morphine arm, with only a reduction in respiratory failure in the high-risk respiratory disease group reaching significance in favour of EA. Enthusiasts interpreted this as confirmation of the value of EA, but the study was widely considered to refute earlier small trials showing improved outcomes with EA.

This month has seen the publication of controversial data from a previous randomised trial (POISE study) challenging the role of EA in reducing morbidity, indicating instead that it may in fact increase morbidity [9]. This study leaves us with more questions than answers in this regard.

NAP3 [10] provided accurate data on neurological complications following central neuraxial blocks, and although the incidence is extremely low, it is greatest in the group receiving thoracic EA for major surgery.

Furthermore technological advances in portable ultrasound have led to a variety of abdominal wall blocks (postero-lateral, subcostal & oblique subcostal TAP as well as rectus sheath blocks), either singe shot or catheter based. Multi-holed catheters have become available to effectively deliver preperitoneal continuous wound infusions of local anaesthetic. These techniques ensure somatic analgesia, dependant on choosing the correct approach for the nature of the incision. Transdermal low dose opiate provides effective and efficient management of the remaining visceral pain, this is short-lived in nature, with any breakthrough pain managed with oral morphine.

Aside from the new array of interventions available to anaesthetists, the past 10 years have seen equally rapid changes in surgical approaches, with laparoscopic approach now the most common, and many of the remaining open procedures performed via transverse incisions. These all have a lower analgesic requirement than the traditional open midline approach.

In fact, it is increasingly clear that for laparoscopic approaches EA is not only unnecessary, but actually lengthens hospital stay as compared to morphine PCA or spinal diamorphine [11], and in my clinical experience the same seems to hold true for open surgery with a transverse incision. Spinal diamorphine seems to provide the best combination of pain experience and duration of hospital stay with the added advantage of single administration.

Adjuvant analgesic therapies may hold additional benefits i.e. gabapentin, ketamine, lidocaine and corticosteroids, with the optimum route, timing and dosages still to be elucidated.

Finally, the failure rate of EA, reported as 20-50% in trials, and the peri-operative hypotension seen in 60% of thoracic EA have added to disillusionment with EA. Hypotension is associated with fluid overload, and vasopressor requirement, which increases stay in high care facilities and healthcare management time.

Our growing armamentarium provides the ability to select horses for courses dependant on the aforementioned factors.

EA still occupies a niche for the foreseeable future for specific colorectal operations e.g. APR due to the combination of incisions, or patients e.g. those with chronic pain conditions or multiple previous abdominal surgery and scarring.

Future trials should compare all new analgesic techniques to EA, and define the role of the alternative adjuvant agents to determine if they warrant widespread use outside of research settings.

  1. Block BM, Liu SS, Rowlingson AJ, Cowan AR, Cowan Jr JA, Wu CL. Efficacy of postoperative epidural analgesia: a meta-analysis. JAMA 2003;290(18):2455-63
  2. Werawatganon T, Charuluxananan S. Patient controlled intravenous opioid analgesia versus continuous epidural anal- gesia for pain after intra-abdominal surgery. Cochrane Database of Systematic Reviews 2005, Issue 1. Art. No.: CD004088.
  3. Rodgers A, Walker N, Schug S et al. Reduction of postoperative mortality and morbidity with epidural or spinal anaesthesia: results from overview randomised trials. MJ 2000;321:1–12
  4. Jørgensen H, Wetterslev J, Møiniche S, Dahl JB. Epidural local anaesthetics versus opioid-based analgesic regimens for postoperative gastrointestinal paralysis, PONV and pain after abdominal surgery. Cochrane Database of Systematic Reviews 2001, Issue 1. Art. No.: CD001893.
  5. Gustafsson U, Scott M, Schwenk M, et al. Guidelines for Perioperative Care in Elective Colonic Surgery: Enhanced Recovery After Surgery (ERASÒ) Society Recommendations. World J Surg (2013) 37:259–284
  6. Nygren J, Thacker J, Carli F et al. Guidelines for Perioperative Care in Elective Rectal/Pelvic Surgery: Enhanced Recovery After Surgery (ERASÒ) Society Recommendations. World J Surg (2013) 37:285–305
  7. Fulfilling the potential: A better journey for patients and a better deal for the NHS. Published on behalf of the Enhanced Recovery Partnership by NHS Improvement 2012.
  8. Rigg JR, Jamrozik K, Myles PS, Silbert BS, Peyton PJ, Parsons RW, et al. Epidural anaesthesia and analgesia and outcome of major surgery: a randomised trial. Lancet 2002;359(9314):1276-82
  9. Leslie K, Myles P, Devereaux P, et al. Neuraxial block, death and serious cardiovascular morbidity in the POISE trial. Br J Anaesth 2013; 111: 382–90
  10. Cook TM,Counsell D, Wildsmith JAW. On behalf of the Royal College of Anaesthetists Third National Audit Project. Major complications of central neuraxial block: report on the 3rd National Audit Project of the Royal College of Anaesthetists. Br J Anaesth 2009; 102: 179–90
  11. Levy B, Scott M, Fawcett W, Fry C and Rockall T. Randomized clinical trial of epidural, spinal or patient-controlled analgesia for patients undergoing laparoscopic colorectal surgery. British Journal of Surgery 2011; 98: 1068–1078