The World Health Organization (2016) made a strong recommendation that adult patients undergoing general anaesthesia for surgical procedures should receive an 80% fraction of inspired oxygen to reduce the risk of surgical site infection based upon a meta-analysis of 15 randomised controlled trails
Five of these trials have been retracted, two of which were by the Mario Schiertoma’s group
The merits of liberal peri-operative inspired oxygen have been disputed
To identify compromised data by Mario Schietroma’s group
To undertake a meta-analysis of other randomised trials of liberal peri-operative inspired oxygen
Literature search for papers with Dr Mario Schietroma as author, included RCTs and observation series published in English
Use of ‘Carlisle method’ to calculate probability of distribution of baseline characteristics for participants use RCTs.
Checked calculations of p values represented in any paper.
Compared figures for duplication
Meta-analysis of liberal trials using Cochrane Collaboration software
Identification of 40 papers that’s fulfilled criteria: 24 RCTS with 5064 participants and 16 observational studies with 1847 patients
Evidence that data intergrity was compromised in 38 of the 40 analysed papers
Meta-analysis of 20 other randomised trials of liberal peri‐operative inspired oxygen in 8357 participants. Pooled results without trials by Schietroma et al. and not, did not show an effect of liberal peri‐operative inspired oxygen on wound infection (OR (95%CI) 0.89 (0.73–1.08); p = 0.23).
Liberal inspired oxygen reduced the rate of postoperative wound infection if trials by Schietroma et al. were included (OR (95%CI) 0.77 (0.61–0.96); p = 0.02 ).
Extreme p values for baseline distributions identified
Identification of replication of graphs and data amongst papers
Only systematic and randomised trials were used in the meta-analysis. All of the reported data in each of the relevant studies were checked. This resulted in the identification of numerous discrepancies
Inherent problems of o Carlisle method: – Inherent with statistics – error may not be secondary to fraud o Meta-analysis
The WHO has already revised its guidelines on liberal peri-operative inspired oxygen following a series of retractions by the Schietroma group.
Ethics behind using Carlisle method to discredit data in a public domain
ARDS (acute respiratory distress syndrome) is associated with high mortality
Oxygenation and carbon dioxide removal can be performed by VV-ECMO (veno-venous extracorporeal membrane oxygenation), however it is associated with significant complications. A previous RCT (CESAR trial – Conventional VentilatorySupport versus Extracorporeal MembraneOxygenation for Severe Adult Respiratory Failure), yielded promising results, however came under criticism for methodological issues and limited conclusions could be drawn.
The question of whether ECMO improves outcomes in ARDS compared to standard lung-protective ventilation remains unanswered.
Aim:The ECMO to rescue lung injury in severe ARDS (EOLIA) trial was designed to determine the effect of early initiation of ECMO in patients with the most severe form of ARDS.
Prospective, randomised controlled trial, 64 centres, mainly France
Ventilated for < 7 days
American-European ARDS definition, 1994
Randomization was stratified according to center and the duration of ventilation before randomization (<72 hours vs ≥72 hours)
Target sample size was 331 patients
Based an expected 60 day mortality rate of 60%, and an estimated 40% mortality in the ECMO group (absolute risk reduction 20%)
For 80% power at an alpha level of 5% and with a group sequential analysis occurring after the randomization of every 60 participants
Stopping rules, using the two sided triangular design methodology, were defined prior to the commencement of the trial. The trial could be stopped due to:
Safety (due to excess mortality in the ECMO arm)
Percutaneous cannulas, with the access cannula inserted into the femoral vein and return cannula inserted into the SVC via the jugular vein
FIO2 (0.21–1) was adjusted to obtain sats between 88-95% and a PaO2 55-80 mmHg
VT set at 6 ml per kg PBW
PEEP set so as not to exceed a Pplat of 28–30 cmH2
NMBAs and prone positioning encouraged for control patients
Trial was stopped early at 249/331 (75% of recruitment) due to predefined futility rules.
Primary outcome: No statistical difference in mortality at day 60
ECMO group 44/124 (35%) vs Control group 57/125 (46%)
Lower relative risk of treatment failure 0.62 (95% CI, 0.47 to 0.82; P<0.001)
Treatment failure was defined as death by day 60 in patients in the ECMO group, and as crossover to ECMO or death in patients in the control group
Lower risk of Renal replacement therapy (RRT) at day 60 (50 vs. 32 days; median difference, 18 days; 95% CI, 0 to 51)
Cross over to ECMO occurred in 35/125 (28%) of control patients
Largest multicenter ECMO RCT to date
Standardised criteria for entry into the trial/ initiation of rescue ECMO
Almost all patients who were randomized to ECMO received it (unlike the previous RCT, CESAR)
Protocolized delivery of ECMO and MV àhence standardised treatments in intervention and control arms (patients were included from both ECMO and non-ECMO centres on the proviso ECMO could be initiated with 2 hours of randomisation).
Underpowered to detect mortality -> trial stopped early! (75% recruitment)
Implausible power calculation (mortality in the control group was 46%, not 60%)
High cross over rate of controls
Lack of blinding
Slow recruitment of 249 patients over 6 years à trial fatigue and/or change of practice
ECMO for severe ARDS showed no significant mortality benefit at day 60 as compared with a strategy of conventional mechanical ventilation.
Both transversus abdominis plane block and intrathecal morphine may produce prolonged postoperative analgesia, but the respective clinical outcomes of these anaesthetic techniques in resource-limited settings are not well described.
This study was performed to compare these two methods of postoperative pain control and find out which was better for the patients in resource-limited setting, and to allow them to develop robust protocols for analgesia in our institution that could be more widely applied.
Prospective randomised study
Inclusion criteria: between 15 and 49 years old, ASA 1 or 2, spinal anaesthetic without sedation, uncomplicated LSCS, able to give informed consent
Consecutive sampling to recruit following decision to LSCS
Patients blinded to study allocation. Blocks done by clinical investigator
Spinal anaesthetic with or without preservative free morphine
Post-op, in recovery room, dermatomal level of spinal block assessed using blunt pin
Pain scores assessed – before block, before discharge from recovery and in ward using numerical rating scale
Intrathecal morphine group received sham block and the TAP block group received B/L TAP block( 15 ml each side of 0.25% bupivacaine with 1:200,000 adrenaline
All patients – Paracetamol 1g and Diclofenac 50 mg at the time of block and at 8,16 and 24 hrs post-op
Reviewed by research assistant – qualified midwife who is blinded to group assignment collected data at 8, 26 and 24 hours
Pain levels – rest, on coughing and on movement (numerical rating score)
Side effects – nausea, vomiting, respiratory depression, sedation and pruritus noted
For statistical power of 80% and type 1 error of 5%- 63 PST each group needed – to allow dropout 65 PST each group recruited
Between group and within group differences in numerical rating scores analysed using repeated measures ANOVA
P value < 0.05- statically significant
Statistically significant low pain score in TAP block group of patients only in 24 hrs during movement. No statistically significant different in pain scores between groups in the 8 and 16 hours period, between side effects, ambulation and patient satisfaction scores
Primary Outcome: Clinically similar for both groups, although pain scores statistically lower in rest and movement at 24 hr with TAP block
Incidence of iatrogenic side effects – low both groups
Satisfaction scores – good in both groups
Rescue Diclofenac PR- requested more frequently both groups at 16 and 24 hrs
Overall paper analysis/review
It was discussed that this study cannot be compared or applied to our current practise in the developed countries with available resources.
We routinely use diamorphine intrathecally and do not have preservative free morphine
But the practice of TAP block in post – caesarean patients who had GA can be encouraged with these results.
Predictors of Difficult Videolaryngoscopy with GlideScope or C-Mac with D-blade: secondary analysis from a large comparative videolaryngoscopy trial Aziz et al. British Journal of Anaesthesia 117 (1): 118-23 (2016)
“Life is simple, but we insist on making it complicated.” – Confucius.
Acute-angle videolaryngoscopes are
designed to overcome some predictors of difficult direct laryngoscopy, and are
intended to improve the view of the relatively anterior airway or when cervical
motion is limited.
However, it’s a different
technique to direct laryngoscopy with different challenges, and it is unclear
what specific factors make acute angle videolaryngoscopy difficult. This paper aimed to identify potential
predictors of difficult videolaryngoscopy.
Secondary analysis of comprehensive data set
from original study which compared 2 acute angle videolaryngoscopy blades in
patients with predicted difficult direct laryngoscopy[i]
study – Single blinded, two-parallel arm,
1100 patients with predicted
difficult airway recruited across three academic institutions in the US; GlideScope
n = 552, C-MAC n=548
Primary outcome – successful
first intubation attempt
All patients going under GA,
with neuromuscular blockade and single lumen tube with predicted difficult
airway defined as 1 or more of the following:
Reduced MO < 3cm (but not <2cm)
Large neck circumference (>40cm M/>38cm F)
Exclusion criteria – known easy
intubation previously, history of failed intubation or difficult BMV, unstable
c-spine injury, age < 18yrs, emergency surgery, planned awake technique,
nasal intubations, MO < 2cm
Laryngoscopists – > 6/12
clinical anaesthesia & undefined level of experience with videolaryngoscopy
Secondary measures recorded
including patient variables, surgical approach, head positioning and provider
characteristics. These were subsequently analysed for this paper
Primary outcome to determine difficult
acute angle videolaryngoscopy – 1st attempt failure or time >60s
to secure airway
Univariate analysis of
potential predictors of difficult vs. non-difficult laryngoscopy carried out
regression model and stepwise model selection techniques conducted to identify independent
predictors of difficult videolaryngoscopy
301/1100 difficult videolaryngoscopy
244 > 60s
27 > 1x intubation attempt
30 > 60s + >1x intubation attempted
Four predictors identified as being associated with difficult videolaryngoscopy – limited mouth opening, type of surgical procedure, laryngoscopist training level, and patient positioning
When compared to the ‘supine neutral’ position, the ‘supine sniffing’ position was associated with an increased risk of difficult videolaryngoscopy (p=0.023, OR 1.625, CI 1.142 – 2.315)
Difficult videolaryngoscopy was associated more with particular surgeries (p=0.0021) when compared with general surgery: ENT/oral surgery (OR 1.891, CI 1.190 – 3.006) and cardiac surgery (OR 6.133, CI 1.847 – 20.367)
Resident anaesthetists have a higher likelihood of success when using videolaryngoscopy compared with attending anaesthetists (p<0.0001, OR 0.546, CI 0.342 – 0.873)
Difficult videolaryngoscopy is more likely to occur in patients with reduced mouth opening (p=0.0225, OR 0.848, CI 1.190-3.006)
Difficulty with supine sniffing position was attributed to a more
challenging blade insertion
ENT/oral surgery also known to
be associated with difficult direct laryngoscopy. The reasons for an association of difficult
videolaryngoscopy with cardiac surgery are poorly explained. The numbers in the original data set for
cardiac surgery are not specified but fall into the category of ‘other’ which
totals just 40. The small data set and
wide CI question the authenticity of this association
A higher likelihood of attendings
encountering difficulty is potentially due to them performing fewer intubations
day to day as they are frequently in a supervisory role
Small MO may hinder initial scope placement and
subsequent tube insertion
Overall paper analysis/review
Large database from which to draw information
from, with appropriate exclusion criteria and a credible aim in trying to
identify predictors of difficult videolaryngoscopy
Study design not powered towards secondary analysis of the data set
Multiple variables not
randomised so the results are associations at best
Criteria for predicting a
difficult airway too broad (could include neck circumference alone)
Unable to assess the predictors
of difficult airway in direct laryngoscopy independently
Primary outcome of defining
difficult videolaryngoscopy as >60s to secure airway arguably too severe in
view of identified potential difficulty, broad range of skill across those
intubating, and lack of required structured training with both
Provider background in academic
institutions and in a well controlled theatre environment not necessarily
transferable to other institutions or clinical areas e.g. ICU/A&E
Not transferable to other types of
videolaryngoscope (eg. Channeled/non acute angle)
Other potential factors
associated with difficult videolaryngoscopy, not in the data set, were not
[i] ‘First-attempt intubation success of video laryngoscopy with
anticipated difficult direct laryngoscopy: a multicentre randomised controlled
trial comparing the C-Mac D-Blade vs the GlideScope in a Mixed Provider and
Diverse Patient Population’ M F Aziz, R O Abrons, D Cattano, E O Bayman, D E
Swanson, CA Hagber, M M Todd, A M Brambrink Anesth Analog 2016: 122: 740 –
There are 20–25, 000 post-operative deaths in the UK each year
High risk surgical patients (12.5% of surgical patients) account for more than 80% of perioperative deaths
There is a move towards greater patient involvement in the own care (e.g. Advanced Care Planning – ‘ACP’)
This is a systematic review with the intention to identify the knowledge and attitudes of health care professionals towards ACPs prior to surgery, and also to identify examples of current practice and barriers to delivery
A review of peer reviewed journal articles in variety of databases and the grey literature
PICOS framework informed the search strategy
They also screened articles for references
There were four main search questions: themes – attitudes if health care professionals (‘HCP’s) to ACPs; level of knowledge of HCPs around ACPs; barriers to ACP discussions and presence of interventions aimed to improve ACP discussions
Of 1566 papers, only 7 met the criteria for inclusion and therefore there is very limited data on which to make conclusions regarding the search questions
There is a lack of evidence in this area
Health care professionals are positive about Advanced Care Planning
There is currently a lack of training and resources to improve the delivery of ACP discussions
Hypersensitivity incidence after sugammadex administration
in healthy subjects: a randomised controlled trial. Min et al British
Journal of Anaesthesia, 121 (4): 749-757 (2018)
A multicentre, double-blind study
Subjects randomised 2:2:1 to Sugammadex
4mg/kg, 16mg/kg or placebo (normal saline)
Doses were administered 5 weeks
apart, to unanaesthetised healthy subjects
Hypersensitivity signs and symptoms were
assessed at 0.5, 4 and 24hrs
Tryptase levels were assessed pre
dose and at 3hrs
IgG and IgE levels checked as an
Hypersensitivity signs/symptoms were
then adjudicated by a blinded committee
The Sampson Criteria were used for
The primary endpoint of the study
was confirmed hypersensitivity
375 subjects recruited
94 subjects with 137 adverse events were sent for review by the independent adjudication committee
Of the 94, 25 subjects were deemed to have “adjudicated” hypersensitivity, with a total of 43 events. This is a hypersensitivity rate of 6.7%.
In the 4mg/kg cohort: 10/151 (6.6%)
In the 16mg/kg cohort: 14/148 (9.5%)
In the Placebo cohort: 1/76 (1.3%)
3 subjects from 16mg/kg required antihistamines/corticosteroids, and did not receive further doses
1 subject had anaphylaxis
Hypersensitivity can occur on first exposure
Signs and symptoms usually presented within minutes (one after 22hrs)
There was no increase in severity with exposures ie no sensitisation. There was no significant tryptase rise. It is therefore unlikely to be mast cell mediated.
They quoted the incidence of anaphylaxis as 1 in 199 or 3.3%
It is unclear from this study if reactions are dose related
They found no IgE antibodies to sugammadex
Limited numbers to subgroup analysis of race or ethnicity
Analysis of the paper and take home thoughts:
It is unclear who the Independent Adjudication
Committee was, or how they reduced the number of hypersensitivity reactions
from 94 to 25.
The authors quoted 1 in 199 or 3.3% anaphylaxis,
however they had one case in 299 subjects receiving sugammadex. I believe that
this figure should therefore be 1 in 299 or 0.33%.
This rate of anaphylaxis is far higher than the approximate
1:10,000 cases seen in NAP6, and is very worrying if sugammadex is to become
more frequently used. We should definitely consider the risks and benefits
prior to administration of sugammadex in our patients.
No Asian subjects were included in the study
Some subjects were unaccounted for in the
The study was funded by Merck and Co. who make
Suxamethonium was used rather than rocuronium which means the results are possibly less applicable in some centres
Should this trial change our practice?
This trial does not inform most of the highest risk situations in which cricoid is employed
IRIS trial does not seriously undermine either of the two camps: cricoid is dangerous (worse view, ineffective) or necessary (not dangerous, might prevent aspiration in higher risk patients, can always be removed)
Cricoid pressure remains recommended by DAS and used routinely in UK obstetric practice (Desai IJOA 2018)
Unless you’re good at guessing, it’s not much use being a detective – Agatha Christie
This study sought to compare the accuracy of pre-operative subjective assessment (METS) with cardiopulmonary exercise testing (CPET, the Duke Activity Index Score (DASI) questionnaire and pre-operative NT pro-BNP levels.
The prognostic accuracy of these values for predicting post-operative morbidity and mortality was also assessed.
An International, multi-centre, prospective cohort study conducted in 25 hospitals (Canada, UK, Australia and New Zealand).
Primary outcome = Death or myocardial infarction within 30 days after surgery
Secondary outcome = Death within one year after surgery
Death or myocardial injury within 30 days
Moderate or severe post-operative complications defined by the Clavien-Dindo classification
Inclusion criteria were patients >40 years of age undergoing elective non-cardiac surgery (with an anticipated overnight stay or longer) with at least one risk factor for cardiac complications.
Exclusion criteria included; planned endovascular approach, pregnancy, cardiac conditions or absolute contraindications to CPET.
All patients recruited underwent pre-operative subjective functional assessment (by an anaesthetist), DASI questionnaire, CPET and NT Pro-BNP measured. Anaesthetist s blinded to these results (except whereby adverse events during CPET warranted unmasking eg. arrhythmia).
Patients were assessed with daily ECG and Troponin until day 3 post-operatively. Further follow up was conducted at 30 days and 1 year.
6548 met inclusion criteria with 1741 consenting to participate.
1401 underwent both surgery and CPET and were included in analysis.
Subjective assessment of functional capacity had a sensitivity of 19.2% for identifying peak oxygen consumption of less than 14 mL/kg per min and a specificity was 94·7%.
Peak oxygen consumption was positively correlated with DASI scores (p<00001), and negatively correlated with NT proBNP concentrations (p<0·0001).
Subjectively assessed preoperative functional capacity had no significant adjusted association with the four main study outcomes.
DASI scores were associated with the primary outcome (OR 0.91 CI 0.83-0.99) and 30-day death or myocardial injury (OR 0.96 CI 0.92-0.99)
NT Pro-BNP was associated with 30-day death or myocardial injury (OR 1.78 CI 1.21-2.62) and 1-year death (OR 2.91 CI 1.54-5.49).
Peak oxygen consumption was associated with in-hospital moderate or severe complications (OR 0.86 CI 0.78-0.97).
Only 27% of patients approached consented to the study. Those that did consent may be a skewed cohort of patients ie. those willing to undergo pre-operative CPET for the purpose of the study.
Study did not adequately explain what happened to patients who were deemed unfit for surgery based on subjective assessment.
The sample size was based on a 5% primary outcome event rate. The actual event rate only 2% meaning the study was underpowered for this.
No adjustments were made for multiple testing.
Subjective assessment may influence complication rates in terms of minimising post-operative risks through augmentation of anaesthetic conduct. An effect that cannot be measured.
The author’s state that functional assessment should not be used for peri-operative risk evaluation. However, CPET failed also failed to predict MI, myocardial injury or death.
CPET did predict moderate to severe post-operative complications based on the Clavien-Dindo classification.
DASI scores proved a useful predictor of cardiac complications and are easily implemented.
Change to clinical practice?
Greater use of the DASI for pre-operative risk prediction should be considered.
Additionally pre-operative NT Pro-BNP should be considered for prediction of post-operative cardiac complications.
“Fullness is always quiet; agitation will answer for empty vessels only.” – Amos Alcott.
Agitation after general anaesthesia is rare but can be associated with self harm and violence against staff. Postoperative agitation is also associated with hyperactive delirium.
Emergence agitation in adult surgical patients has not been as well studied as in children.
The aims of this study were to:
evaluate the prevalence of emergence agitation in adults after general anaesthesia
assess for potential associations between patient and perioperative factors and agitation
describe the postoperative course of adult patients who have had agitation episodes
The authors examined electronic case records for 207,569 adult patients undergoing surgery between July 2010 and September 2016 at the Mayo Clinic Hospital, MN, USA. They identified 510 cases of agitation in this group that were matched to case controls by age and procedure.
The overall incidence of agitation was 510 patients (0.25%).
Variables associated with agitation were substance misuse, cognitive impairment, obesity, psychiatric problems, fall risk and the postoperative presence of an endotracheal tube, urinary catheter, nasogastric tube or chest drain.
Postoperative agitation was associated with postoperative delirium and pulmonary complications.
The authors suggest identification of risk factors for agitation will allow development of processes to ensure safe care.
This paper is hypothesis generating but the methodology does not permit causative associations to be made. We felt that several of the associations identified were plausible in line with our clinical experience. The association of agitation with postoperative delirium and pulmonary complications is of clinical interest as postoperative morbidity is itself associated with reduced longterm survival.
The authors acknowledge in their discussion the likelihood of spurious associations being made when large numbers of variables are included. Although we felt several of the associations were clinically plausible it is not possible to establish causation and there are likely to be unmeasured confounders.
Unfortunately the study design does not allow the association between agitation and age or procedure type to be established.
The primary outcome measure is agitation as defined in part by RASS score. One of the criteria for RASS +3 is pulling at tubes. We were not surprised therefore to see presence of tubes as a significant predictor of agitation.
This paper highlights the problem of postoperative agitation in a patient population similar to our own. The methodology does not provide sufficiently robust evidence to recommend change in practice or policy at this time.