Article Notes
- Analysis of 927 confirmed symptomatic cases of COVID-19 demonstrates BNT162b2 is highly effective with 91.3% vaccine efficacy observed against COVID-19, measured seven days through up to six months after the second dose.
- Vaccine was 100% effective in preventing severe disease as defined by the U.S. Centers for Disease Control and Prevention and 95.3% effective in preventing severe disease as defined by the U.S. Food and Drug Administration.
- Vaccine was 100% effective in preventing COVID-19 cases in South Africa, where the B.1.351 lineage is prevalent.
- Vaccine safety now evaluated in more than 44,000 participants 16 years of age and older, with more than 12,000 vaccinated participants having at least six months follow-up after their second dose.
- pKa - 8.5 (9% nonionised @ 7.4)
- Octanol water coefficient - 39 (so 40x lipid solubility of morphine)
- phenylpiperidine opioid
- Dose - 25-100 mg (10% morphine potency). Limit 1000 mg 1st day, then 600 mg/day there after.
- Absorption - IV, IM, epidural, po (55% biov)
- Distribution - Vdss 4.5 L/kg. Crosses placenta - foetal 80% of maternal.
- Protein binding - 60%
- Onset 10 min ; Offset 2-3 h
- Metabolism - ß½ 3 h; N-demethylation to norpethidine and then hydrolysis to norpethidinic acid; also direct hydrolysis to pethidinic acid. Renal elimination.
- Norpethidine - ß½ 15 h; 50% analgesic properties, 2x convulsant effects.
- Clearance - 20 mL/kg/min (same as morph & fentanyl)
- Mech - mu and kappa agonist, causing potent spinal and supraspinal analgesia.
- CNS - more euphoria, less N/V than morphine. No miosis, but may cause mydriasis (pupil dilation -atropine-like kappa action). No EEG changes like morphine. ⇡ latency & amplitude of SSEPs.
- NB: has LA action, so can be used as sole agent for neuroaxial block.
- anti-shivering effect (kappa)
- CVS - ⇣ MAP (> than morphine) due to histamine release & alpha adrenergic blockade (vasodilation). Inc HR (atropine like effect). Large doses depress myocardial contractility. May cause hypertensive crisis in those on MAOIs.
- vasodilation
- tachycardia
- depress myocardial contractility
- Resp - potent resp depressant - greater effect on TV than RR. Histamine release. Chest wall rigidity.
This interesting prospective simulation & equipment study is by way of the University of Freiburg. Schmutz et al. investigated how effective five different second generation supraglottic airway devices (SADs) performed in two common airway manikins: the TruCorp AirSim® and the crowd favourite, Laerdal's Resusci Anne® Airway Trainer™.
While ventilation was achieved in all SAD-manikin combinations, the Resusci Anne® Airway Trainer™ was associated with better and more consistent performance for SAD position, participant subjective assessment and ease of gastric tube insertion for most of the SADs. The TruCorp AirSim® did however achieve better leak pressures across most of the SADs (LMA® Supreme™, Ambu® AuraGain™, i-gel®, KOO™-SGA & LTS-D™).
But then, what are the implications for airway simulation training? The researchers correctly note that:
The most important quality of a manikin is the ability to simulate the real-world conditions and thus to give the trainee an authentic feedback.
The bottom line for SAD manikins?
While considering how manikin choice and SAD availability match with your aims for simulation training, the bigger picture is that the primary goal of any manikin-SAD coupling is real-life fidelity – and for that reason, participant subjective assessment is king. And so in this study at least, the Resusci Anne® Airway Trainer™ wins.
Daniel Jolley
This reassuring study published in Nature by researchers from Wash U Med investigated persisting COVID immunity following the Pfizer mRNA vaccination (BNT162b2). Turner et al. looked at the presence of not only circulating antibody-secreting B cells, but also germinal centre B cells found in the axillary lymph nodes of 14 study volunteers.
While the persistence of mRNA-vaccine induced immunity to SARS-CoV-2 has already been demonstrated to last at least 6 months, and likely 12 months, we just do not yet have the data to know if or when vaccine boosters will be required beyond that.
Turner's study is particularly exciting because they found spike-protein binding B cells in the germinal centre of draining lymph nodes in all 14 post-immunisation participants for the full 15 weeks of the study. The germinal centre response was so vigorous and persistent that the researchers believe this could represent COVID-protection lasting for years.
"Ellebedy said the immune response observed in his team’s study appears so robust and persistent that he thinks that it could last for years. The researcher based his assessment on the fact that germinal centre reactions that persist for several months or longer usually indicate an extremely vigorous immune response that culminates in the production of large numbers of long-lasting immune cells, called memory B cells. Some memory B cells can survive for years or even decades..." – Dr Francis Collins, NIH Directors Blog
This study builds on the same team's earlier work (Turner 2021 May) looking at bone marrow plasma cells in those who have recovered from mild COVID infection, also showing a long-lived immune response.
COVID persistent immunity takeaway:
Although COVID-19 and developed vaccines have been circulating for only 12-18 months, these immune-response studies give some hope that the miracle of mRNA vaccines may not only be in their efficacy, but also in the longevity of protection.
Daniel Jolley
Pfizer and BioNTech reported that phase 3 trials of their mRNA SARS-COV-2 vaccine showed:
Daniel Jolley
Although interesting and perhaps relevant to settings which require motor block resolution before discharge from PACU (or when there are bupivacaine shortages), the practical relevance of this study is questionable.
Notable in this French study is the extended duration of PACU stay after caesarean section: more than 2 hours in the prilocaine group, and 3 hours in the bupivcaine group! It is unclear whether this is routine post-CS care, or specific to the study design to allow for motor block assessment.
Also of note, the caesarean sections were "...performed using Misgav-Ladach technique with externalisation of the uterus" which may again make this study less relevant in settings where it is routinely accepted that avoiding uterine externalisation makes for better patient experience.
Daniel Jolley
Following their important 2020 study of the risk of surgery for COVID patients, the COVIDSurg Collaborative reports on their prospective cohort study aiming to determine the optimal delay for planned surgery after COVID infection.
Once again this was an international (116 countries), multicentre, prospective cohort study including all surgery types, over 140,000 patients, and 3,127 post-COVID. Once again the 30-day postoperative mortality was sobering: even in the 5-6 week post-COVID group, 30-day mortality was dramatically higher (OR 3.6, 2.0-5.2) compared to those without a COVID diagnosis. Worryingly the risk was consistent among both low-risk and high-risk surgical groups.
Although after the 7-week mark postoperative mortality was similar to non-post-COVID patients (OR 1.5, 0.9–2.1), those with persisting COVID symptoms still suffered a 6.0% 30-day mortality (3.2–8.7). (30-day mortality among non-COVID patients was 1.5% (1.4-1.5).
Post-COVID surgical timing takeaway:
Surgery should be delayed for at least 7 weeks after COVID, although those with persistent COVID symptoms will still have more than twice the 30-day mortality than those without.
Daniel Jolley
The most relevant takeaway from this meta-analysis is really just how poor a lot of the evidence around resuscitation and CPR is (not for lack of effort, but because of the obvious limitations of research around critical-event and end-of-life medicine). Not only was the analysed evidence of low certainty but notably all seven RCTs were manikin studies.
Manikins are designed for resuscitation education and training, not for physiological fidelity. Even if this study had shown an improvement in compression depth for different surfaces, it's relevance to CPR in flesh-and-blood humans would be no less questionable.
Daniel Jolley
Kataife et al. (2021) describe a cognitive aid for better managing perioperative haemorrhage, the Haemostasis Traffic Light algorithm. Using a simulation-based RCT across two centres (University Hospital Zurich & the Italian Hospital of Buenos Aires, N=84), they showed that using the HTL improved case solutions (OR 7.23, 3.82-13.68), quickened therapeutic decisions, (HR 1.97, 1.18-3.29), improved therapeutic confidence, (OR 4.31, 1.67-11.11) and reduced workload perception.
The aim of the HTL is to improve both situational awareness and decision making, by integrating clinical judgement and point-of-care testing (ROTEM) within an accessible, structured algorithm.
Haemostasis Traffic Light takeaway:
Kataife's study again shows the benefit of cognitive aids, particularly in critical, time-sensitive situations. The anaesthesia and critical care community's historical resistance to decision-support tools requires challenge.
Daniel Jolley
Interesting Cochrane meta-analysis looking at PONV prophylaxis from German (Weibel et al. 2021) that included almost 100,000 study participants across 585 trials. Interesting not so much because it confirms much of what we already new (or assumed, based on our common PONC prophylaxis drug choices), but because it reassures us that side-effects from commonly used PONV drugs are low to non-existent.
Takeaway: granisetron is probably the best single-agent or in combination with other agents because of it's efficacy (better than ondansetron), low-cost, long duration, and absent side-effects.
Daniel Jolley
Matthew Smith
Pethidine (Meperidine) is a phenylpiperidine synthetic opioid first synthesized in 1938. Although widely used in the 20th century, it has fallen out of favour over the past decade due to abuse potential, limited advantages over other opioids and the existence of toxic metabolites.
A. Physiochemistry
B. Pharmacokinetics
C. Pharmacodynamics
Daniel Jolley