We are delighted to announce that the 41st Western Anaesthesiology & Critical Care Symposium (WAS) is on – in person – at Glenlo Abbey Hotel, Galway, on March 25th and 26th. Because of the short timescale for organising the meeting, the meeting will feature mostly local talent – all of your controversial favorites plus some new exciting speakers. It will be a great opportunity to learn something new and catch up with a few (dozen) old friends.

Full details are HERE.

Thanks for the appeal, anaesthesiawest is now reactivated.

From the “who would have guessed it” category come the idea of naloxone as an analgesic.

There have been several previous studies (see below) showing that extremely low doses of naloxone appeared to have analgesic properties, but no real explanation of how this might be possible.

The most recent interesting article is this one here, recently published in the journal of pain, showing +(-) naloxone reverses multiple models of chronic neuropathic pain in rats,

http://www.jpain.org/article/S1526-5900(12)00522-6/abstract

Ultra low dose naloxone attenuates morphine tolerance in rats

http://www.sciencedirect.com/science/article/pii/S0091305710001486

Low dose 0.25mcg/kg/hr naloxone reduces opioid consumption, nausea and vomiting in 90 abdominal hysterectomy patients.

The first article showing this was by Gan et al in 1997. They looked at 60 patients who had a PCA along with infusions of varying doses of naloxone or saline. It was designed to look for a reduction in itch and nausea but as well as finding this found the group that got the lowest dose of naloxone also had a reduction in opioid use, with equivalent pain score

http://journals.lww.com/anesthesiology/Abstract/1997/11000/Opioid_sparing_Effects_of_a_Low_dose_Infusion_of.11.aspx

Following Paul Myles’ paper in Anesthesiology in 2007 – that demonstrated bad outcomes in patients anaesthetised with nitrous oxide (click here), “experts” clamoured to demand that we stop using the stuff in our clinical practice. Their opinions were enhanced by the ENIGMA trial, that claimed increased risk of myocardial infarction in patients receiving nitrous (click here); following adjustment for the usual factors.  I have been personally accused of “poisoning” my patients by continuing to administer nitrous. Hence, it was with great relief that I read this paper (click here) in this month’s anesthesia and analgesia.
Turan and Colleagues evaluated almost 50,000 patients who had noncardiac surgery at the Cleveland Clinic over a 4 year period (2005 and 2009). Of the patients that had general anesthesia, 17,00 were given N₂O (45%) and 21,000 were not (55%). Of each group, 10,000 patients were propensity score-matched  on 30-day mortality and a set of 8 in-hospital morbidity/mortality outcomes.
The results were surprising. Patients that were given N₂O intraoperatively had decreased odds of 30-day mortality (odds ratio [OR]: 97.5% confidence interval, 0.67, 0.46–0.97; P= 0.02), compared with no nitrous. In addition, patients that received  had a17% (OR: 0.83, 0.74–0.92) reduced odds of experiencing major in-hospital morbidity/mortality than non-nitrous (P < 0.001). In particular, the risk of pulmonary complications with significantly lower in patients who received nitrous.(OR, 95% Bonferroni-adjusted CI: 0.59, 0.44–0.78).
Ok – so this was a propensity score analysis induced fluke – right? In the same issue of A&A we have a second paper that analysed the POISE trial outcomes (click here). 30% of the 6000 patients in the study received nitrous – and there was NO association between the gas and adverse outcomes. A fairly biased editorial in A&A, written with the help of Paul Myles, whose group is the only one that has demonstrated bad outcomes with nitrous, dismembers the Turan paper.
Nitrous oxide has been around for 160 years. I am not aware that there is a pandemic of death and MI amongst the patients of those of us who use the stuff. In any case, I think that this paper, at the very least, suggests that the jury is still out on the subject.

Several years ago while in Galway I first came across the concept of remote ischaemic preconditioning (RIPC). This is the concept that subjecting one part of the body to a brief period of ischaemia (eg 3 cycles of 5 minutes of an arm tourniquet above systolic pressure, followed by 5 minute deflations) can protect the rest of the body from subsequent ischaemic insults.

In the past couple of years there has been an explosion of interest in this fascinating idea and some truly exciting results from initial trials (see examples below). However, as with most new areas subsequent studies have not been quite as impressive as initial results. This seems to follow the pattern of most new findings in medicine: “It’s amazing!” followed by discovery of some setback or complication, leading to “It’s awful / useless!”, and finally “It’s OK if used in the right way for the right patients”.

The background to the discovery of ischaemic preconditioning comes from interventional cardiologists, who noted that patients who had “stuttering” myocardial infarctions seemed to do better than those who just had a single large MI.

Further work on anaesthetised dogs by Murry in the mid 1980s showed that 4 episodes of 5 minutes of coronary artery ligation before a 40 minute ligation reduced infarct size to a quarter of the size seen in the control group.

http://circ.ahajournals.org/content/74/5/1124.abstract

The ischaemia seems to produce 2 periods of protection, an early window out to 6 hours and a late window out to around 72 hours.

Since then studies have emerged showing that a protective effect occurs even if the organ rendered initially ischaemic is not the organ which suffers the final insult – in fact it appears that arm or leg ischaemia can protect the heart, lungs and kidneys. This is termed remote ischaemic preconditioning. What I like about this technique is that most attempts to protect the heart so far have been drug based and very one dimensional, relying on say beta blockers or statins to target a certain receptor. This technique harnesses an intrinsic protective mechanism, rather than on us trying to pick a single mediator to convey benefit, the ischaemic insult releases a range of known and unknown protective substances. It would be very difficult to replicate this complex soup with a drug. In addition  this is almost risk free and should avoid the nasty surprises such as the finding of increased stroke and mortality found in the POISE trial which has halted the enthusiasm for beta blockers.

The study which first kicked off interest in this area was from 2007 by Hausenloy et al. 57 CABG patients were randomising to RIPC via an arm tourniquet and were found to have a 43% reduction in post operative troponin release.http://www.sciencedirect.com/science/article/pii/S0140673607612963

Also in 2007 a RCT by Ziad in 82 patients having open AAA repair showed that 2 cycles of 10 minutes of common iliac artery clamping prior to aortic crossclamping reduced MI from 27% to 5% and renal impairment from 30% to 7% compared to control.

http://circ.ahajournals.org/content/116/11_suppl/I-98.short

A recent meta-analysis of RIPC for CABG incorporating 10 studies and 693 patients showed a reduction in troponin release, however the studies with better blinding showed a smaller effect size, suggesting the benefit may be lower than original trials suggested.

Another meta-analysis of 17 cardiac and vascular trials showed a reduction in markers of myocardial injury, a reduction in MI (7.9% vs 13%) and (for AAA repair) a reduction in renal injury. There was no evidence of publication bias.

http://www.ncbi.nlm.nih.gov/pubmed/22294530

RIPC also appears to have some effect in preventing contrast nephropathy in 100 patients with renal impairment having coronary angiography, with renal injury rates of 40% in control vs 12% in RIPC. This has implications for ICU patients requiring contrast CT scans.

http://circ.ahajournals.org/content/early/2012/06/25/CIRCULATIONAHA.112.096370.short

Finally, a study just out in Anesthesiology looked at 62 patients having elective infrarenal AAA repair and found an improved a/A ratio and improved markers in intestinal injury in the RIPC group compared with control

http://europepmc.org/abstract/MED/23353795/reload=0;jsessionid=K8cOgeieWh27t1SMmKZ5.2

Of interest, a dose finding study is currently underway in Australia and NZ looking at defining the optimum “dose” of RIPC for best benefit.

There are some other interesting implications of RIPC. There has been a recent trend to orthopaedic surgeons doing knee replacements without tourniquets. Could this “improvement” in fact lead to worsening post-op outcomes due the loss of protection from myocardial ischaemia in the highest risk 72 hours post operatively, the “late” RIPC protection time?

In summary RIPC offers the latest hope in achieving the holy grail of anaesthesia- reducing post operative cardiovascular complications. The biggest advantage of RIPC over previous attempts, such as beta blockers, widespread preoperative revascularisation and regional techniques is simplicity and lack of harm. It’s hard to envisage anything bad coming from some brief cycles of tourniquet inflation and as the Lancet summarised it, it might mean “an arm and a leg can save the heart”.

Our ICUs are crowded by patients that are slow to liberate from mechanical ventilation. In North America, such patients are often transferred to long term mechanical ventilation facilities (LTAC) – where they are weaned to liberation. There are many strategies for weaning tracheostomised  patients from mechanical ventilation – a progressive reduction in pressure support, intermittent tracheal mask (trach collar) trials, external CPAP etc.

Martin Tobin has, for many years, questioned the now conventional wisdom of progressive pressure support weans, and in this weeks JAMA his group have published a paper comparing Volume Assist Control Ventilation with intermittent tracheal mask trials to progressive pressure support weaning. The patients in the pressure support group (PSG) started, if they were able to tolerate it, pressure support ventilation at 14cmH2O. Tolerance to wean was checked every 6 hours, and 2cmH2O decrements of PS were applied up to a maximum of 6cmH2O per day. Once the pressure support reached 6cmH2O, a 5 day vent liberation process began. In the tracheal mask group (TMG), patients were put on tracheal mask  for up to 12 hours per day for 2 days (then back on assist control) and on day 3 started on the 5 day vent liberation programme.

The primary outcome was weaning duration, defined from the first day of randomization to the day the patient was successfully weaned. Weaning was considered successful when patients breathed without ventilator assistance for at least 5 days. If the patients had not liberated by day 45, this was considered “failure to wean.”

Three hundred and twelve patients were randomized, of which one third died while in the study (equal numbers each group). Among the entire group of randomized patients (n = 312), median weaning time was shorter in TMG versus PSG: 15 days (IQR, 8-25) vs 19 days (IQR, 12-31), P = .004.. Among patients who completed the study (n = 194), median weaning time was shorter in TMG vs PSG: 13 days (IQR, 8-30) vs 19 days (12-43), P = .006.

Weaning time had no effect on survival at 6 and 12 months.

Impression: this article suggests that weaning patients using decrements of pressure support is not aggressive enough and that weaning in more likely to be successful with unassisted tracheal mask. Although, unsurprisingly, this had no effect on survival, a 6 day reduction in ventilator times translates into considerable resource savings – particularly with ICU/HDU beds are very scarce (as in our hospitals). Whether or not patients should be weaned from assist-control or high levels of pressure support appear moot: I doubt that it makes a difference. I continue to see any value for using external CPAP through a t-piece as a vent liberation process: there is not a shred of supportive evidence.

The media are constantly harping on about the obesity epidemic – “two in three of us are fat – this is going to lead to an explosion of obesity related morbidity – heart disease, cancer, cerebrovascular disease, crumbling joints etc.” It never seems to occur to the same talking heads on television and in print media that life expectancy continues to improve worldwide, without any great new medical advances over the past 2 decades (during which the obesity epidemic emerged). In perioperative medicine and critical care we have data that an “obesity paradox” exists – that individuals with a BMI between 25 and 35 (overweight and grade 1 obesity) have lower mortality rates in perioperative medicine (references 1. Here, 2. Here) and critical illness (references 1. Here; 2 Here; 3 Here; 4. Here). The reasoning why overweight and mild obesity (being chubby) may confer benefit is an increase in physiology reserve, delivered in part by an increase in lean body mass. As patients become heavier (body mass index; BMI>35, grade 2 and 3 obesity), they start manifesting mass related injury and metabolic disease. Metabolic syndrome unquestionably increases long term risk (here).
But what of the general population? Life insurance companies continue to penalize chubby folks based on actuarial figures from the 1960s – it that fair? It turns out that it is not. Hold your breath – a 2.88 million patient meta analysis performed by a group of US researchers and published in last week’s JAMA (here), has completely moved the goalposts for desirable BMI. In terms of Hazard Ratio (where HR of 1 = BMI 20-25), BMI of 25-30 had a HR for all cause mortality of 0.94 (lower; CI 0.91-0.96). BMI  30-35 had HR 0.95 (lower; but CI 0.88 – 1.01 NS). BMI 35-40 HR 1.29 (higher CI 1.18-1.41). In other words – overweight patients had LOWER all cause community mortality than BMI 20-25. Being obese up to BMI 25 did NOT increase mortality risk, and only individuals with BMI >35 had increased risk.

People – you need to face up to it: OVERWEIGHT IS THE NEW “NORMAL.” Perhaps “Chubby Chandler (above)” was the healthy one.

More comments to follow.