Article Notes
- β-lactam allergy, particularly penicillin allergy is the most common perioperative patient-reported sensitivity, in up to 35% of patients.
- Unneccessary switching to non-β-lactams for surgical prophylaxis is not cost-free, and is contributing to the rise of c. difficile and vancomycin-resistant Enterococcus (VRE).
Patient history of penicillin allergy is of variable quality, and often does not allow the allergy to be ruled-out.
Step 1 – differentiate drug side effects from allergy. Isolated nausea, vomiting or diarrhoea are usually side effects.
Step 2 – identify the type of hypersensitivity.
- Most drug reactions are Type 4 (T-cell mediated), delayed from 2 hours to days after exposure. Mostly benign cutaneous symptoms (eg. rash) that do not necessarily require avoiding future β-lactam exposure, except in the case of Stevens-Johnson syndrome.
- Type 1 (IgE-mediated) hypersensitivities are immediate (minutes to 2 hours) but less common, causing urticaria, angioedema and/or anaphylaxis. Future exposure should be avoided.
- Type 2 (cytotoxic) and Type 3 (immune complex) are much less common, and present with more serious, though delayed, reactions (days to weeks).
Take home: Mild symptoms (eg. rash developing more than 2h after exposure) probably do not require β-lactam avoidance. If there is a history of moderate or severe reaction, then avoiding all β-lactams is wise.
Of interest: Although R1 side-chain similarity is the main contributor to penicillin-cephalosporin cross-reactivity, importantly, 1st generation cephazolin has a different R1 side-chain and has been reported to not cross-react. Other cephalosporins share side-chains with specific penicillins.
Finally, stop giving IV test doses. It makes no sense from a safety point of view and offers no useful information.
- The utility of fibrinogen measurement as an early indicator of coagulopathy and severe PPH, especially <2 g/L.
- The value of point-of-care testing, such as with ROTEM®.
- The typical maintenance of normal PT & APTT until 4-5 L of blood loss, unlike fibrinogen which was abnormal after ~2 L loss.
- The rarity of needing to replace factors other than fibrinogen even in severe PPH. FFP can usually be safely withheld in moderate-to-severe PPH when POCT is available.
- The value of fibrinogen concentrate over cryoprecipitate, although without value in pre-emptive formulaic treatment.
- The value and practicality of measuring blood loss versus estimation.
This meta-analysis (unsurprisingly) confirms that pre-operative troponin levels are post-operatively associated with both major adverse cardiac events and mortality risk.
This sounds obvious, why should we care?
First, there's a difference between evidence and that vague feeling we call common-sense that a disproportionate number of our clinical decisions are based upon.
Surgical patients are getting older and sicker. We need better tools for risk stratifying patients before surgery to improve perioperative planning. Most importantly (though not exclusively) reliably identifying biomarkers for risk allows closer postoperative surveillance and monitoring – which may alter outcomes.
Why troponin?
We already know that troponin I and T are markers of cardiac damage, and unlike brain natriuretic peptide (BNP), troponin assays are readily available in most healthcare settings.
Ok, you convinced me... what did they find?
Analysing 10 studies totally 10,371 patients, they found an association between preoperative troponin elevation and MACE (OR 6.9), and short-term & long-term mortality (OR 4.2 & 2.5). Note though that the confidence intervals were quite wide.
There's always a but... the included studies were all observational in nature, used a variety of troponin assays, and the results were quite heterogenous across the 10. Most importantly, even assuming troponin is an accurate preop risk marker, we don't yet know whether that knowledge will allow us to alter outcomes for these patients.
Collins et al share their insights from 10 years of Cardiff research and pragmatic clinical experience managing postpartum hemorrhage.
Why is this important?
PPH incidence is increasing globally and is still the number one cause of maternal death. Many routine PPH transfusion practices are dogmatic and based upon non-pregnant trauma data. Applicability to PPH is at best questionable.
Of interest they note:
The take-away: Plasma fibrinogen is generally a more important target than PT or APTT in most PPH cases. (Placental abruption is an important exception.)
Interesting physiological tidbit... because normal term fibrinogen is 4 g/L and FFP fibrinogen is 2 g/L, undirected FFP transfusion in PPH could theoretically contribute to dilutional hypofibrinogenemia.
An interesting exploration of the surgeon-anesthesiologist relationship, framed in terms of it being the critical dyad of the operating theatre team.
Cooper explores the positives and negatives, the stereotypes that each craftgroup holds of the other, and the ways in which these translate to team performance.
Most significantly, Cooper makes the point that when highly functional this relationship can lead to the highest quality patient care, but at its worst, dysfunction can lead to extreme harm and compromise patient safety.
Cutting to the chase...
This large, retrospective study with propensity-matched controls found NO difference in breast cancer survival between inhalataional and intravenous anesthetic techniques.
Why is this still important?
Following Exadaktylos' eye-popping 2006 retrospective, along with a few in vitro studies, anesthetists have been a little anxious that anesthetic technique choice could potentially have a such significant effect on cancer recurrence. To date, other trials have not replicated Exadaktylos' original results.
What was studied this time?
Yoo et al performed a retrospective study of 5,331 breast cancer patients over a 8 year period, looking at the relationship between anesthetic technique and both 5-year recurrence-free and overall survival.
There was no difference for either survival metric between inhalational or intravenous anesthesia.
So does this settle it?
Not yet. Although large and high quality, this is still a retrospective study with all the compromises that this brings.
Be smart
While we await results from prospective, randomized trials, we should not be distracted by the magical promise of one technique over another, and instead address the very real impact that anesthesia can have on patient Return to Intended Oncological Therapy (RIOT).
This controversy-starting retrospective study reported a 30% reduction in 3 year recurrence-free survival after undergoing mastectomy for primary breast cancer in patients who received a traditional general anaesthetic with morphine analgesia, compared with those receiving a regional (paravertebral) technique.
Although plausible biological mechanisms have been suggested and even demonstrated in vitro, the huge treatment effect is yet to be replicated in better quality retrospective or prospective trials.
Evidence to date does not (yet) support this trial’s findings.
"An extraordinary claim requires extraordinary proof." – Marcello Truzzi
Why this is interesting...
In many ways, human albumin might be the perfect colloid fluid – and concentrated 20% albumin could be the ideal resuscitation fluid in the critical care setting, where fluid overload is otherwise a common consequence. Because of its high relative concentration, the intravascular expansion effect of 20% albumin is roughly double its infused volume, unlike 4% or 5% albumin.
In the SWIPE trial Mårtensson et al showed that even in the leaky-capillary state of critical illness, resuscitation with 20% albumin decreased fluid needs, lessened positive fluid-balance states, and was not associated with harm when compared to 4-5% albumin.
What did they do?
This was a well designed multicentre trial across three adult Australian & UK ICUs. 321 patients were randomized to either 20% or 4-5% albumin resuscitation during their first 48h in ICU.
Bottom line:
Probably the most important takeaway is simply that resuscitation with 20% albumin is practical and results in no patient harm compared with 4-5%. The 576mL median lower difference in fluid balance is unlikely alone to be dramatically consequential.
Nonetheless an important first step before larger studies can look at morbidity and mortality outcomes.
Cautiously note though that for logistic reasons the trial was open label, so treating clinicians were well aware of which fluid they were using. Additionally, they were given free reign to choose additional resuscitation fluids (crystalloid or synthetic colloid) as the clinical situation required.
This update to their 2011 meta-analysis supports their conclusion that aspirin modestly reduces myocardial infarction when used for primary prevention, but at the expense of increased risk of intracranial and major bleeding.
What's the big deal?
Low-dose daily aspirin is one of the most common drugs taken for cardiovascular disease prophylaxis. Although it's role in secondary prevention is well established, until now it's use for primary prevention in the fit and healthy was controversial – even though it was widely taken by patients and their family doctors alike!
What did they do?
The ASPREE trial (Aspirin in Reducing Events in the Elderly) enrolled 19,114 across the U.S. and Australia, randomizing to 100mg daily aspirin or placebo. Participants were 56% women, median age of 74 and had median follow-up for almost 5 years.
What did they find?
Aspirin did NOT improve either disease-free survival OR reduce cardiovascular disease, although it did increase risk of major hemorrhage. Similarly no benefit was seen for all-cause mortality (in fact, a surprising increase crept in...).
The one group that did see a drop in cardiovascular events were diabetics with no previous cardiovascualr history but who suffered a counteracting increase of major hemorrhage.
But... this study specifically targeted the elderly, who suffer higher rates of antiplatelet-related hemorrhage. Modest benefits have previously been reported in a recently updated meta-analysis though again with a simultaneous increase in major and intracranial bleeding.
Final word... daily aspirin likely causes net harm in the healthy elderly.
What's the story here?
Growing evidence points to significant anti-depressant effects of several anesthetic agents, including ketamine, nitrous oxide, propofol and isoflurane. These may provide avenues for use as novel antidepressants or lead to development of new agents, supplanting other therapies such as ECT.
Why is this important?
Major depression and its consequences contributes to significant disease burden worldwide. Depression prevalence is increasing globally, with one third suffering treatment-resistant depression, unresponsive to modern antidepressant drugs.
Ketamine appears to produce both a fast antidepressant and antisuicidal effect, persisting for up to 1 week. The effect appears dose-responsive in the 0.1 to 0.75 mg/kg range.
Isoflurane when administered to achieve burst suppression (1.5-2 MAC) may have antidepressant effects in 75% of those treated, and achieved full remission in 50% in one 2013 study, comparable to ECT but with fewer cognitive side effects.
N2O use in one small pilot study resulted in depression improvement, likely through similar mechanisms as ketamine. Similarly, propofol-induced burst suppression has also shown an antidepressant effect similar in magnitude to isoflurane.
Bottom line: Several anesthetic agents appear to offer significant antidepressant benefits, which may lead to more mainstream use and supplant ECT. Anesthesiologists will be need to be aware of these effects as they become involved in their provision.