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Welsh Anaesthetic Trainees Journal Club

Journal Club: 8th August 2018

The cardiopulmonary exercise testing grey zone; optimising fitness stratification by application of critical difference

British Journal of Anaesthesia 2018;120(6):1187 – 1194  doi: 10.1016/j.bja.2018.02.062

Presented by: Dr Hannah Saitch

Background

  • Cardiopulmonary exercise testing acts as an aid to clinical decision making pre-op.
  • American Heart Association name it as a “clinical vital sign”
  • Original study – found 18% mortality in elderly with Anaerobic threshold (AT) <11m O2 / Kg, 0.8% mortality with AT >11 ml O2/ Kg (Older et al 1993)
  • Other studies have reported an AT 9-11 ml O2/kg as a cut off for higher versus lower risk.
  • Cardio respiratory fitness is dynamic and therefore will vary – this is the biological difference.
  • The analytical difference is the difference which occurs with repeated testing for the same sample – affected by the accuracy.
  • The Critical Difference (CD) considers the analytical difference and the biological difference and is defined as random variation around a homeostatic point indicative of a change that must occur before a true difference of clinical significance can be claimed. No previous study has looked at CD for CPET testing.

Design and Setting

Two Arm Study

Arm 1

  • Aim to establish CD
  • Analytical Difference (CVA) – Simulated expired and inspired gases passed through Medigraphics Ultima Metabolic cart – 25L/min. 8 repeated trials of 10 resp cycles, middle 5 breaths averaged. Aim to simulate peak of CPET testing
  • Biological Difference(CVB)– 12 healthy volunteers, 3 CPET tests. All at different times of day, at least 24 hrs apart. Wasserman Protocol. Medgraphics equipment used – VO2 peak, oxygen uptake efficiency slope, peak oxygen pulse. Aerobic threshold manually calculated using V slope method.

= k √CVA2+CVB2

K – constant

Arm 2

213 consecutive patients from colorectal pre-assessment CPET testing in single centre.  Retrospective analysis

CPET equipment and protocol used as per arm 1

Reference metrics from American Heart Association

  • VO2- AT <11ml O2/Kg
  • VO2 peak <16ml O2/Kg/min
  • VE/VCO2 – AT >36

Statistical Analysis

  • IMB SPSS used
  • Distibution normality assessed using Shapiro-Wilk W test
  • Time of day analysis in arm 1 analysed using Bonferroni corrected repeated measures analysis
  • Continuous data – mean or median used
  • Categorical data – absolute values used
  • Sample size for Power 80% with P<0.05

Interventions

  • Revised fitness stratification corrected by +/- CD to threshold boundaries. Area in between named “indeterminate fitness”
  • Compared patients for current and revised models

Outcomes

  • Patients who had false negative and false positive results when CD applied
  • False Positive– patients originally stratified as fit but with negatively corrected become unfit
    False Negative – patients originally stratified as unfit but with positive correction become fit
  • Patients in area of indeterminate fitness

Results – Arm 1

Critical Differences as follows:

  1. AT – 19%
  2. VO2 Peak – 12.5%
  3. VE/VCO2 – AT – 10.2%

Results – Arm 2

Based on application of critical differences to results:

  1. For AT there were 69 (32%) false positives and 59 (28%) false negatives
  2. For VO2 Peak there were 35 (16%) false positives and 33 (15%) false negatives
  3. For VE/VCO2 – AT there were 40 (20%) false positives and 37 (17%) false negatives

The following revised stratification model was developed

  1. AT – unfit – <9.2, indeterminate fitness 9.2 – 13.6, fit ≥6
  2. VO2 Peak – unfit <14.2, indeterminate fitness 14.2 – 18.3, fit ≥ 18.3
  3. VE/VCO2 – AT – unfit ≥ 40.1, indeterminate fitness 32.7 – 40.1, fit <32.7

The revised stratification model was applied to the patients CPET tests

Discussion

  • Highlight potential for incorrect fitness stratification
  • Mean values were close to threshold therefore large no of patients moving into indeterminate groups
  • AT most incorrectly stratified, then VO2 Peak, then VE/VCO2 – AT
  • Revised stratification confirms potential clinical impact

Strengths

  • Clinically relevant question, although these variations would have been present throughout all previous studies determining CPET interpretation therefore
  • Power 80%, P <0.05
  • Appropriate statistical tests
  • CD calculation – standard mathematical formula

Weaknesses

  • Study arm 1 not comparable to patients in 2 (all young, healthy males in 1) plus small numbers in 1. Potential for vastly different biological variation in population in arm 2 with average AT of 11. Post study evaluation suggests larger groups (39 in each arm) should be used for randomised controlled exercise trials.
  • Data collected on single system therefore only applicable to MedGraphics equipment
  • No metabolic calibrator for equipment used (although 2.2% range of results is within expected accuracy range)
  • Retrospective data from study arm 2. States that standard protocol followed but can this be guaranteed? No mention of staff being trained to trial protocol for patients in study arm 2.
  • Does not analyse surgical outcomes in light of indeterminate risk.

Implications

  • No assessment of clinical outcomes in view of indeterminate risk
  • Highlights need for consideration of multiple factors within risk stratification
  • Consider CPET results as a dynamic range – Particularly in post operative planning

Potential for clinical impact

Moderate – fitness should not be considered as a single point estimate. With an increasingly elderly and co-morbid population CPET testing is likely to increase and therefore potential for impact there however does not provide the answer of how to manage patients in the indeterminate risk group therefore further research may be indicated.

 

 

 

 

 

 

 

 

 

 

 

 

Journal Club: 5th July 2018

Dabigatran in patients with myocardial injury after non-cardiac surgery (MANAGE): an international, randomised, placebo-controlled trial

Lancet 2018;391:2325-34 doi:10.1016/S0140-6736(18)30832-8

Presented by: Dr James Lloyd

Background

  • Myocardial injury after non-cardiac surgery (MINS) is a relatively newly described diagnosis, having only been described about 4 years ago
  • The diagnosis includes myocardial infarction and isolated ischaemic troponin elevation occurring within 30 days after surgery, but does not include perioperative myocardial injury due to non-ischaemic causes for example caused by sepsis, or rapid heart rate.
  • It is common, estimated at around 8 million cases internationally every year, and carries an increased risk of mortality.
  • This is the first randomisedcontrolled trial to address this group of patients.

Design & Setting

  • A multicentre, international, placebo controlled randomised control trial involving 1754 patients

Subjects

  • Patients over 45, who had received non cardiac surgery, and were within 35 days of what the authors term MINS (Myocardial Injury after Non cardiac Surgery).
  • MINS is defined as having either elevated troponin with ischaemic signs or symptoms, ischaemic electrocardiographic changes, or new or presumed new ischaemic abnormality on cardiac imaging or an isolated elevated troponin measurement without an alternative explanation.

Intervention

  • Patients were assigned either the intervention arm which was 110mg of Dabigatran twice daily for up to two years, or matched placebo.
  • Patients were then also randomised to receive either 20mg of omeprazole once daily, or placebo, as part of a separate study.

Outcomes

  • The primary outcome was a major vascular complication (This was defined as a composite of vascular mortality, and non-fatal myocardial infarction, non-haemorrhagic stroke, peripheral arterial thrombosis, amputation, and symptomatic venous thromboembolism).
  • The primary safety outcome, to monitor the side effect profile of the intervention, were a composite of life-threatening, major, and critical organ bleeding.

Results

  • A major vascular complication occurred in 97 (11%) of 877 patients allocated to dabigatran and in 133 (15%) of 877 patients allocated to placebo (HR 0·72, 95% CI 0·55–0·93, p=0·0115)
  • In addition, Dabigatran did not increase the risk of life-threatening, major, or critical organ bleeding (primary safety outcome) compared with placebo (HR 0·92, 95% CI 0·55–1·53, p=0·78)
  • In the analysis of the secondary outcomes Dabigatran was shown to increase the risk of minor bleeding, clinically non-significant lower gastrointestinal bleeding, and dyspepsia.
  • The subgroup analysis shows that the hazard ratios are not statistically significant for patients receiving dual antiplatelet therapy, or for patients who showed only an isolated troponin rise.

Conclusions

  • In patients identified as having MINS, instigating a treatment of 110mg BD dabigatran reduced the probability of a major vascular complication, without increasing the risk of major, or life threatening bleeding.
  • The number needed to treat with dabigatran to prevent one major vascular complication was 24, whereas the number needed to harm (i.e. to cause major, rather than life threatening bleeding) is 54.
  • The subgroup analysis fails to reinforce the concept of routine monitoring of troponin, as the patients identified only by a troponin rise did not show any benefit from the intervention.

Strengths

  • A large, well blinded randomised control trial, with good length of follow up

Weaknesses

  • Trial terminated early due to slow recruitment and withdrawal of funding
  • Because of the early termination the primary outcome measures for the trial were altered part way through
  • The subgroup analysis shows benefit for one group, but not another, suggesting two different sets of pathology

Implications

  • That unless routine screening of perioperative troponin levels is instigated 90% of MINS events will be missed.
  • That treating these patients with BD Dabigatran 110mg will reduce vascular complications.

Potential for impact

I don’t think this is really very clear, for two main reasons;

  1. Although the subgroup of patients who had ischaemic changes on ECG showed benefit from the treatment, they also had quite low levels of treatment with traditional secondary prevention medication, for which there is already lots of evidence.
  2. The group of patients who were only identified with troponin changes did not show any benefit from the intervention, which means there is little point starting this costly screening process when the authors are keen to point out that this is the only trial investigating the treatment of this group of patients.

 

 

Journal Club: 27th June 2018

Time elapsed after ischaemic stroke and risk of adverse cardiovascular events and mortality following elective non-cardiac surgery

 Journal of the American Medical Association. 2014;312(3):269-277

 Presented by: Dr Anthony Byford-Brooks

Background

  • Cerebrovascular accident (CVA) is recognised as a major risk factor for major adverse cardiac event (MACE) following non-cardiac surgery. It is included in the Lee revised cardiac risk index, and is also analogous to the perioperative risk to patients with recent myocardial infarction (MI) +/- percutaneous coronary intervention (PCI). The ‘safe’ timing of surgery post-CVA is not well defined like it is with MI.
  • Cerebral autoregulation is known to be impaired up to 90 days following CVA, but the significance of this in the perioperative setting, and the impact of surgery and anaesthesia on autoregulation is not well studied.
  • This study aimed to look at safety and importance of time between stroke and surgery.

Design & Setting

  • A retrospective, Danish nationwide cohort study from 2005-2011.
  • All patients above 20 years of age undergoing elective non-cardiac surgery (n=481,183).
  • Danish healthcare system keeps all information on national registries, and five were accessed in order to gather data on patient backgrounds, types of surgeries, medicines used and anaesthetic records.

Subjects

  • All patients over 20 years of age having elective non-cardiac surgery from 2005-11. ICD-10 used to identify those patients who suffered ischaemic stroke in the past. Haemorrhagic stroke and TIA were excluded. Stroke diagnosis excluded if time elapsed to surgery >5yrs.
  • Five population groups, made to be roughly analogous with post-MI risk:
    1. No prior stroke
    2. Stroke ❤ months of surgery
    3. Stroke 3-6 months of surgery
    4. Stroke 6-12 months of surgery
    5. Stroke >12 months of surgery
  • Grouping for use of pharmacological agents based on use of antihypertensives, antithrombotics, oral hypoglycaemics and diuretics.
  • Significant comorbidities included organ failures, AF, IHD, COPD, PVD, anaemia, DM and metastatic disease
  • Surgery performed subdivided by specialty, excluding trauma, intracranial surgery, tracheostomy/gastrostomy and urgent upper GI. Also grouped into low, intermediate and high risk surgeries.

Outcomes

  • Primary outcomes were all-cause mortality and MACE within 30 days.
  • MACE subdivided into nonfatal acute MI, nonfatal ischaemic stroke and cardiovascular death.

Results

  • Of the 481,183 surgeries performed, 7137 (1.5%) were performed in patients with prior history of stroke.
  • These patients were on average 16 years older, male, on cardiovascular meds and had more comorbidities.
  • Almost a quarter of the stroke and non-stroke group had >1 surgery in the 5 year period.
  • Incidence rates (Stroke vs. Non-stroke group):
    • Ischaemic stroke: ❤ months – 149.6x higher
    • All-cause mortality: ❤ months – 12.6x higher
  • Odds Ratios:
    • 30-day MACE (<3months vs >12 months): 14.23 vs 2.47
    • Low (9.96), Intermediate (17.12) and Higher (2.97)
    • Recurrent strokes ❤ months: 67.6
    • No association between prior stroke and acute MI
    • Cardiovascular death: 4.35
    • Splines for OR levelled off roughly after 9 months.
    • Alcohol and smoking as covariates altered OR very little.
    • Use of blood-thinning agents and statins has a significant impact in reducing risk.
  • Relative Risk:
    • 30-day mortality: 1.8-fold increased risk in stroke group.
    • 30-day MACE: 4.8-fold increased risk in stroke group.
  • Stroke patients with AF at less risk than those without AF.
  • Those with recurrent strokes at higher risk.

Conclusions

  • Elective non-cardiac surgery <9 months after stroke carries significant risk of MACE and mortality.
  • Low or intermediate surgery carries equal or higher relative risk than high-risk surgery.
  • Patients with AF have lower risk perhaps due to nature of stroke (thrombotic vs atherosclerotic) and higher likelihood of subsequently being on appropriate drugs. 

Strengths

  • Good access of the Danish databases to address a question not previously asked.
  • Large cohorts.
  • Use of data analysis that helps quantify risk over a protracted period.
  • Consideration of additional factors (drug history, comorbidities).
  • Authors identify study weaknesses.

Weaknesses

  • No data on whether surgeries performed took time elapsed from stroke into consideration.
  • Patients may not have been fully worked up or optimised prior to surgery, particularly those <3months of stroke e.g. echo.
  • No data on in-hospital drug administration, only long-term meds at home
  • Undiagnosed comorbidities would skew data.
  • Guidelines for perioperative use of antithrombotics in Denmark changed during study period.
  • Not able to determine if ischaemic stroke is embolic or atherosclerotic e.g. AF vs PVD.
  • Type and conduct of anaesthesia not accounted for.

Implications

Although stroke is known to be a risk factor, a way of quantifying risk based on time since event, as well as what patient factors adjust this risk, can improve patient safety. The timing is similar to acute-MI +/- PCI for those at highest risk, but some risk does remain up to 9 months.

Potential for Impact

There is a potential for impact here. A forming evidence base on the degree of risk following stroke could help mitigate adverse events by allowing for optimisation of patients following stroke, or delaying of surgery, particularly those of lower risk. It also gives food for thought for emergency surgery and highlights the need for a detailed history of CVA and informed discussion on perioperative risk for those patients.

Journal Club: 20th June 2018

Association of Frailty with Failure to Rescue After Low-Risk and High-Risk Inpatient Surgery.

JAMA Surg. doi:10.1001/jamasurg.2018.0214

Presented by: Dr Steve Young

Background

This is a retrospective data set study from American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). It investigated the role of frailty in post operative outcomes

Design & Setting

It used the above data set from 2005-2012. It looked at patients in the data, assessed their frailty using the Risk Analysis Index and then compared their outcomes along with type of procedure (low risk or high risk)

Subjects

  • In patients undergoing general, vascular, cardiac, thoracic and orthopaedic operations 2005-2012 at 600 hospitals in the United States.
  • Final analysed data set just under 1 million patients.

Intervention

This was an observational study

Outcomes   

Complication rates after inpatient surgery

Results

Increasing frailty increases your rate of complications

Conclusions

Preoperative patient frailty is an important risk factor for post operative complications

Strengths

  • Very large comprehensive data set.
  • Statistically significant outcomes
  • Clinically significant outcomes
  • Relevant to our practice

Weaknesses

  • Retrospective observational study
  • No intervention
  • The outcome is pretty obvious

Implications

Although probably a useful study to confirm obviousness, I’m not sure how much this adds to my practice

Potential for impact

As above, I am not sure this adds much but it does confirm what we thought.

Journal Club: 13th June 2018

The association of pre-operative home accelerometry with cardiopulmonary exercise variables

Anaesthesia. 2018;73(6):738-745. doi: 10.1111/anae.14181. 

Presented by: Dr Megan Burton

Background

This study looks at monitoring activity in patients before major surgery with the aim to identify patients at high-risk of peri-operative morbidity and mortality.

Cardio-pulmonary exercise testing (CPET) is used to access cardiac and pulmonary reserve and identify patients at high-risk of mobility and mortality. However CPET is restricted to particular hospitals and select patients.

This study’s aim is to try and use home-worn accelerometers as a cheaper and more accessible way of measuring pre-operative physical activity to predict adverse outcome in patient undergoing major surgery compared with cardio-pulmonary exercise testing.

Design & Setting

A UK based study comparing methods of measurement of pre- operative cardio-pulmonary fitness. Compares variables measured using a waterproof chest accelerometer which is fitted to the patient at their CPET and is worn continuously at home fore a 72 hour period.

These measurements are compared with Pre-operative cardio-pulmonary testing variables:

  • Peak power
  • Peak Oxygen consumption
  • Anaerobic threshold
  • Ventilatory equivalents for O2 and CO2
  • Predicted values for peak oxygen consumption.

Subjects were also asked to complete two self-reporting questionnaires to estimate physical activity and functional reserve:

  1. The Duke activity status index (DASI)
  2. The SF-12.

The accelerometer measures are compared to PRET measurements using persons correlation coefficient.

 

Subjects

Recruited participants were recruited from patients attending the pre- operative cardiopulmonary exercise clinic.

  • 50 recruited majority of whom were male (42).
  • 48 completed the 72 hours wearing the accelerometer.
  • Mean age 70,
  • Majority ASA 2’s and 3’s.
  • Mean DASI score = 37.6 and mean SF-12 = 44.4.

DASI is a subjective estimate of functional capacity. Maximum score is 58.2, and a score of 37.6 suggests pretty high functionality. i.e. able to walk up a hill, do yard work, climb a flight of stairs.

The SF-12 is a subjective measure of health and well being. the mean score for the US general population is 50.

Intervention

Participates had a waterproof accelerometer strapped to their chest for 72 hours. Accelerometer measures were collected and compared to cardio- pulmonary testing variables, which were collected from a standard CPET involving incremental exercise on a stationary bike whilst attached to ECG, pulse oximetry and gas analysis.This provided information on a number of variables: Peak power, Peak Oxygen consumption, anaerobic threshold, ventilator equivalents for O2 and CO2 and predicted values for peak oxygen consumption. They also asked participants to complete self reporting questionnaires: The Duke activity Status index and the SF-12 to look at baseline exercise capacity.

Outcomes

Primary outcome

Explore the associations between accelerometer variables measured at home with variables measured during cardiopulmonary exercise testing in patients scheduled for major surgery.

Secondary Outcome

Assess the acceptability and feasibility of using an accelerometer to determine the pre-operative activity level of patients.

Accelerometer frequency measures were categorised into activity levels (this categorisation has been previously documented and has shown to be 81–93% accurate compared to of videotape analyses)

Activity levels were categorised into Active, Stationary, and Lying, from accelerometer frequencies using an algorithm. These were compared with CPET variables: Peak power, Peak Oxygen consumption, anaerobic threshold, ventilator equivalents for O2 and CO2 and predicted values for peak oxygen consumption. These were compared using persons correlation coefficient to give an r value.

NB. Persons correlation coefficient is a measure of the linear correlation between two variables X and Y. It has a value between +1 and −1, where 1 is total positive linear correlation, 0 is no linear correlation, and −1 is total negative linear correlation.

Results

Accelerometer values:

  1. Lying 42.6% (12.6%) – No correlation with CPET variables
  2. stationary 53.0% (11.9%) – No correlation with CPET variables
  3. Active 4.7% (3.1%) – linearly correlated with: peak power, Peak O2 consumption, and anaerobic threshold ( r=0.5-0.7). Some correlation with ventilator equivalents for O2 and CO2 (r=<0.5). And no correlation with Predicted values for peak O2 consumption.

Conclusions

Pre-operative accelerometry is feasible and the study did find an association with fitness measured by cardiopulmonary exercise tests. But the accelerometer measurements only correlated when the participants were active, when they were inactive the measure’s did not correlate with CPET variables. There was a large amount of inactivity recorded; 95% were inactive for 24hrs of the day and sedentary for 99% of the time.

Overall the main conclusion they were able to produce was that pre-operative accelerometer is feasible and that its the duration of moderate intensity activity is likely to be the most useful measure of fitness.

 

Strengths

  1. Adequately powered study: The study calculated that a cohort of 47 participants would have 80% power to identify a Pearson’s correlation coefficient ≥ 0.4 at p ≤ 0.05 between an activity variable and either anaerobic threshold or peak oxygen consumption. They achieved 48 participants.
  2. The study was able to show correlation when active between the accelerometer readings and the CPET measurements with an r value of 0.5-0.7 which was the primary aim of the study.
  3. The secondary aim was the access the acceptability and feasibility of using an accelerometer to determine the pre-operative activity level of patients. Patients apparently reported that wearing an accelerometer at home for three consecutive days was acceptable (although 1/4 didn’t complete the 72hr period!).

Weaknesses

  1. Correlation coefficients are not robust so the r value can be misleading and although is widespread method in the analysis of comparing medical testing methods it is generally not considered a very good way.
  2. Chest accelerometers may not pick up activity where the chest is still but the legs are active- such as cycling. Considering patients underwent their CPET on a bicycle it seems unfortunate to miss potential data in this way.
  3. 72 hours is a snap shot of activity and doesn’t predict the potential for activity. Many did not complete the full 72 hour period so may miss some activity. And may not be a good predictor of cardio-respiratory reserve.
  4. One-quarter of the participants did not wear the accelerometer for 72 hrs, which might have limited how representative the results were for the total cohort.

Implications

I’m not convinced the chest accelerometer has the potential to replace CPET in predicting function reserve but perhaps there is a place for their use in the implementation in preoperative cardio-pulmonary exercise interventions. The study suggests that longitudinal methods of daily activity will be used to supplement formal cardiorespiratory fitness assessments but I don’t think theres enough evidence from this study to use it as a productive measure.

Potential for impact?

It may be useful as an activity measuring method in future research for the implementation of pre-operative exercise interventions.

Journal Club: 6th June 2018

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery (RELIEF)

 New England Journal of Medicine. DOI: 10.1056/NEJMoa1801601.

 Presented by: Dr Helen Ivatt Clinical Fellow Anaesthetics

 Background

Traditional intravenous fluid regimes have been shown to deliver up to 7 litres fluid on the day of surgery resulting in significant tissue oedema and weight gain.  In 2003 Brandstrup et al demonstrated a halving of the complication rate with a near zero fluid balance compared with a judicious fluid regime1. Several other small studies demonstrated a similar effect 2-4.  Fluid restriction in major abdominal surgery is supported by recent consensus statements, and the enhanced recovery after surgery (ERAS) pathway which is widely adopted as a standard of care during major abdominal surgery also takes this approach5.  However, the evidence is not comprehensive or conclusive therefore the RELIEF trial was designed to compare outcomes using a restrictive v’s liberal fluid regime in high risk patients undergoing major abdominal surgery.

 Design & Setting

RELIEF is a large, multicentre, randomised, international, single blind, pragmatic trial, with patients randomly assigned to either restrictive or liberal fluid groups, stratified by site and by planned high dependency unit (HDU) or intensive care unit (ICU) admission.

The study ran from May 2013 – Sept 2016 in 47 centres across seven countries and included 3000 participants.

 Subjects

Inclusion criteria

Adults undergoing elective major abdominal surgery that included a skin incision with an expected duration of at least 2 hours and an expected hospital stay of at least 3 days who were at increased risk of complications defined by at least one of the following:

  • ≥70 years
  • Coronary artery disease
  • Heart failure
  • Diabetes (On oral hypoglycaemics +/- Insulin)
  • Preoperative serum creatinine >200μmol/L
  • BMI >35kg/m2
  • Preoperative serum albumin <30g/l
  • Anaerobic threshold <12ml/kg/min

Or two or more of the following:

  • ASA 3 or 4
  • Chronic respiratory disease
  • BMI 35kg/m2
  • Anaerobic threshold 12 – 14 mL/kg/min
  • Aortic or peripheral vascular disease
  • Preoperative Hb <100g/L
  • Preoperative serum creatinine 150-199 μmol/L

Exclusion criteria

  • Time-critical surgery
  • ASA 5
  • Chronic renal failure requiring dialysis
  • Pulmonary or cardiac surgery
  • Liver resection
  • Minor or intermediate surgery (e.g. lap cholecystectomy, TURP, inguinal hernia repair.)

Randomisation

Patients were randomly assigned in a 1:1 ratio using a web based service.  Permuted blocks stratified by both site and planned post op area of care (ICU, HDU or Ward) were used to ensure that prognostic factors and patient characteristics were balanced between groups.

Power calculation

Sample size calculation was based on the groups own data and other published studies.  A type I error of 0.05 was set along with an expected disability free survival at 1yr of 65% and a hazard ratio of >1.25.  This estimated that 1300 patients would be required in each group to provide 90% power thus a target recruitment of 2800 patients was set to make up for losses.

As the event rate was significantly less than expected (14.6% rather than an expected 35%) the sample size was increased to 3000 to provide 80% power.

Intervention

Participants were assigned to either Liberal or Restrictive fluid groups:

Liberal fluid group

  • 10ml/kg bolus of crystalloid at the start of surgery.
  • 8ml/kg/hr crystalloid until the end of surgery (reduced if clinically indicated after 4hrs)
  • Bolus colloid/blood was used intraoperatively to replace blood loss (mL for mL)
  • Maintenance 1.5ml/kg/hr for at least 24 hrs (reduced or increased according to hypovolaemia, fluid overload etc).
  • Treat hypotension with a fluid bolus in the first instance

Weight >100kg both bolus and maintenance limited to that for a 100kg patient.

Restrictive (‘zero balance’) intravenous fluid group

  • ≤5 mL/kg bolus of crystalloid at the beginning of surgery
  • 5 mL/kg/hr was to be administered until the end of surgery
  • Bolus colloid/blood was used intraoperatively to replace blood loss (mL for mL)
  • Maintenance 0.8mL/kg/hr until cessation of fluid within 24 hours (Reduced or increased according to hypovolaemia, fluid overload etc)
  • Treat hypotension with vasoconstrictor in the first instance.

Outcomes

Primary endpoint

Disability free survival at 1yr after surgery (Measured by the WHODAS score).

Secondary endpoints

  • All-cause mortality at 90 days, and survival up to 12 months after surgery.
  • Composite and individual incidence of sepsis, surgical site infection, anastomotic leak and pneumonia.
  • AKI
  • Pulmonary oedema
  • Duration of mechanical ventilation
  • Day 3 CRP
  • Lactate within 24hrs of surgery
  • Blood transfusion following surgery
  • Unplanned admission to HDU/ICU within 30 days of surgery.
  • Total HDU/ICU stay.
  • Total hospital stay up to day 30.
  • Quality of recovery on days 1, 3 and 30.

 Results

2983 out of 3000 met criteria for a modified intention to treat population (patients had to be both randomised and undergo induction of GA). There were no significant baseline differences and the loss to follow up was small at 3.3% (82 patients).

In the first 24 hrs there was a significant difference in median fluid infusion (3.7L v’s 6.1L P<0.001).

There was no significant difference between groups for the primary endpoint of disability free survival. Subgroup analysis also failed to find a difference.

Acute kidney injury occurred in 124 (8.6%) patients in the restrictive group and 72 (5%) patients in the liberal group (p<0.001).

The need for renal replacement therapy and the incidence of surgical site infection was significantly greater in the restricted group but significance was lost after adjustment for multiple comparisons.

No significant difference was found with any of the other secondary outcomes.

 Conclusions

The authors conclude that in patients at increased risk for complications while undergoing major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen 1 year after surgery. However, the restrictive regimen was associated with a higher rate of acute kidney injury.

 Strengths

  • Large multicentre, multinational randomised design.
  • Modified intention to treat approach.
  • Primary outcome of disability free survival may be seen as more meaningful endpoint than the traditional outcomes of morbidity and mortality.
  • Correction for multiple testing carried out.

 Weaknesses

  • Clinicians could not be blinded to volume administration, which could have lead to bias in outcome recording however research staff responsible for the primary outcome were blinded to allocated treatment.
  • The surgeries performed were heterogenous which risks a cancelling out of effect, and a lack of generalizability.
  • Fluid administered after the first 24hrs was not recorded.
  • The event rate was lower than previously documented in the literature meaning that the study was less well powered than previously thought and increases the chance of a type II error.
  • The ERAS protocol was not adhered to in a large number of patients though this was not significantly different between groups

 Implications

The findings of this fairly robust study do not support the previously accepted notion that fluid restriction is better that judicious IV infusion.  There are a number of reasons why this may be the case; previous papers have reported greater infusion volumes on the day of surgery (up to 7L intraoperatively), and much greater weight gains than demonstrated in the current paper (4-6kg cf 0.3-1.6kg).  Some of the reason for this weight gain will be fluid volume related but it may also be related to the fact that surgical techniques are minimally invasive and so reduces the metabolic stress that leads to fluid retention.

Therefore we could conclude that with modern surgical techniques and fluid regimes, modest fluid administration that exceeds a zero balance is no longer associated with harm to the patient and may reduce the incidence of AKI. The paper should, however, not be used to support excessive IV administration.

Potential for impact

This is a well designed large multicentre study which is the first of it’s kind.  It is applicable to our high risk patients and though it has limitations it rejects the current trend for fluid restriction and advocates a more modest approach to fluid administration in the 24hrs post surgery.

 References

  1. Brandstrup B, Tønnesen H,Beier-Holgersen R, et al. Effects of intravenous fluid restriction on postoperative complications: comparison of two perioperative fluid regimens: a randomized assessor-blinded multicenter trial. Ann Surg 2003;238:641-648.
  2. de Aguilar-Nascimento JE, Diniz BN, do Carmo AV, Silveira EA, Silva RM. Clinical benefits after the implementation of a protocol of restricted perioperative intravenous crystalloid fluids in major abdominal operations. World J Surg 2009;33:925-930.
  3. Lobo DN, Bostock KA, Neal KR, Perkins AC, Rowlands BJ, Allison SP. Effect of salt and water balance on recovery of gastrointestinal function after elective colonic resection: a randomised controlled trial. Lancet 2002;359:1812-1818.
  4. McArdle GT, McAuley DF, McKinley A, Blair P, Hoper M, Harkin DW. Preliminary results of a prospective randomized trial of restrictive versus standard fluid regime in elective open abdominal aortic aneurysm repair. Ann Surg 2009;250:28-34.
  5. Gustafsson UO, Scott MJ, Schwenk W, et al. Guidelines for perioperative care in elective colonic surgery: Enhanced Recovery After Surgery (ERAS) Society recommendations. Clin Nutr 2012;31:783-800.

Journal Club: 30th May 2018

Abnormal routine pre-operative test results and their impact on anaesthetic management: An observational study.

Indian Journal of Anaesthetics 2018;62:23-8. DOI: 10.4103/ija.IJA_223_17

Presented by: Dr Benjamin O’Donovan, ST4 Anaesthetics

Background

In spite of guidelines from the ASA and NICE, and a lack of evidence for ‘routine’ pre-operative investigations they are still frequently carried out. These investigations may identify previously unknown abnormalities resulting in changes to pre-operative management. This study aimed to assess the prevalence of abnormal test results and their impact on the peri-operative management of patients undergoing elective surgery.

Design & Setting

An observational prospective study, in a tertiary care teaching hospital.

Subjects

414 consecutive patients aged 12 years or older, male or female, attending preassessment clinic for non-cardiac surgery were used.

Exclusions

  • Pregnant patients
  • Bedridden or immobile patients (unable to assess body weight)
  • Patients under the age of 12 years old

Intervention

Data collected:

  • Demographics
  • ASA grade
  • Grade of surgery (NICE classification)
  • All investigations and results prior to being declared fit for surgery were noted including:
    • Haemoglobin less than 10g/dL
    • Platelets less than 100
    • Elevated blood sugar
    • Abnormal TFTs
  • Newly diagnosed comorbidities from investigations were noted.

NB: New diagnoses of hypertension were not counted

Outcomes

  • An abnormal result was said to be ‘impactful’ if it resulting in referral, delay, further investigations, retesting or changes in anaesthetic management plan.
  • This was said to be a significant impact if the resulting change was in the perioperative anaesthetic management.
  • An abnormal but potentially expected result leading to a change in management was not counted.

Results

  • 345 (11.6%) of results were abnormal
    • 56 abnormalities had an impact
    • 20 had a significant impact.

NNI for significant impact was 21 and detecting new abnormality was 28. Average

Conclusions

  • Over half of patients in the study have abnormal test results
  • 8% of tests have an impact on patients
  • 67% of tests have significant impact.

Strengths

  • National Journal
  • Prospective study
  • Appropriate study power calculation
  • Largely reasonable exclusion criteria
  • Positive subject to investigate in terms of rationalising healthcare expenditure.

Weaknesses

  • Observational study
  • Single centre
  • Unclear if protocol for requesting pre-operative investigations
  • 12 seems an odd age for cut off of lower limit
  • Not affecting peri-operative management doesn’t necessarily mean no significant patient impact.

Implications

We over investigate our patients by the parameters of impact/significant impact set out in this study.

Potential for impact

Given that this study indicates that patients are over investigated at pre-operative assessment there would be the potential for significant cost-saving by reducing the number of investigations requested.

 

 

Journal Club: 23rd May 2018

Perioperative aspirin therapy in non-cardiac surgery: A systematic review and meta-analysis of randomized controlled trials

International Journal of Cardiology 2018;258:59–67 

doi: 10.1016/j.ijcard.2017.12.088 0167-5273

 Presented by: Dr L Jones

Background

  • Cardiovascular and bleeding events are amongst the leading complications during surgery
  • Aspirin is the cornerstone of secondary prevention of cardiovascular disease
  • As an irreversible cyclooxygenase-I inhibitor, aspirin poses a bleeding risk
  • For non-cardiac surgery aspirin’s benefits and bleeding risks remain unclear

Design & Setting

  • A systematic review and meta-analysis of randomised controlled trials
  • Aspirin v no aspirin in non-cardiac surgery
  • All cause mortality, cardiovascular mortality, arterial ischaemic events, venous thromboembolic events and bleeding events separately evaluated

Subjects

  • 7 relevant prospective randomised controlled trials
  • 28302 patients
  • Intermediate risk cardiovascular-risk surgery

Intervention

  • Different for every trial but a variation on aspirin at various doses v no aspirin

 Outcomes

  • All cause mortality (All trials)
  • Cardiovascular mortality (All trials)
  • Perioperative MI (All trials)
  • Major Bleeding (All trials)
  • Cerebrovascular events (6 trials)
  • Peripheral arterial events (3 trials)
  • Venous thromboembolic events (4 trials)

 Results

  • All-cause mortality (3.7% vs. 3.8%; odds ratio (OR) 0.97, CI 0.86–1.10) and cardiovascular mortality (2.0% vs. 2.1%, OR 0.92; CI 0.78–1.09) were not different in aspirin vs. no aspirin groups.
  • Arterial ischemic events showed no differences, including myocardial infarction (2.5% (aspirin) vs. 2.5% (no aspirin)), cerebrovascular events (0.6% (aspirin) vs. 0.6% (no aspirin)) and peripheral arterial events (0.2% (aspirin) vs. 0.3% (no aspirin)).
  • Aspirin significantly reduced the risk for venous thromboembolic events (VTE; 1.5% (aspirin) vs. 2.0% (no aspirin); OR 0.74, CI 0.59–0.94, p = 0.02).
  • Perioperative major bleeding was significantly more frequent in aspirin groups (4.4% vs. 3.7%; OR 1.18, CI 1.05 to 1.33, p = 0.007).

 Conclusions

  • Aspirin showed no difference in terms of mortality v no aspirin for intermediate risk non cardiac surgery
  • Aspirin significantly reduced the risk for VTE but also had a significantly higher major bleeding risk

 Strengths

  • Meta-analysis of RCTs
  • High sample size
  • Easy to measure primary outcomes

 Weaknesses

  • Not all trials included secondary outcome measures eg. VTE risk
  • Variance in doses of aspirin per study
  • Some studies (PEP, POISE-II and STRATEGEM) used other anticoagulants as well as aspirin

 Implications

  • Aspirin showed no mortality benefit therefore the initiation/ continuation of aspirin in the perioperative period for intermediate risk surgery is not recommended.
  • Aspirin showed a 25% risk reduction in VTE for orthopaedic surgery and therefore should be considered as prophylaxis alongside other anticoagulants

 Potential for impact

  • Conclusive evidence for stopping aspirin in the preoperative period for intermediate risk surgery. This helps in decision making in the pre assessment clinic.
  • Consideration for adding aspirin to VTE prophylaxis protocols

Journal Club: 16th May 2018

Incidence and risk factors of anaesthetic-related perioperative cardiac arrest. European Journal of Anaesthesiology 2017;34:1–7 doi:10.1097/EJA.0000000000000685

 Presented by: Dr R Dean-Paccagnella

Background

  • Many studies have analysed perioperative mortality in speciality sub-groups, but few have looked at unselected patient populations. Many studies have excluded patients undergoing cardiac surgery.
  • Previous papers have studied perioperative mortality but have not independently reviewed the incidence and risk factors of cardiac arrest.
  • This study aims to measure the incidence of perioperative cardiac arrest in an unselected anaesthetic population and retrospectively identify significant risk factors.

Design & Setting

  • Retrospective cohort study of non-ITU patients undergoing anaesthesia between January 2007 and December 2012 at a single tertiary hospital in Cologne, Germany.

Subjects

  • 169,000 adult and paediatric patients underwent anaesthetic procedures within the time period.
  • Study population (n 318) was identified by the screening of critical incident report forms, performed by the authors.
  • Cases were categorised into 1. “anaesthesia related” (directly caused by an anaesthetic procedure), 2. “anaesthesia contributory” (caused by both surgical and anaesthetic events) or 3. “anaesthesia contributory” (possibly caused by factors under the control of the anaesthetist).

Intervention

  • Undifferentiated anaesthetic procedures were analysed retrospectively.

Outcomes

  • Incidence of pulselessness requiring chest compressions within 24hours after anaesthetic procedure.

Results

  • Incidence of perioperative cardiac arrest was 5.8/10,000 anaesthetic cases (95% CI 4.7-7.0).
  • Significantly increased risk of perioperative cardiac arrest was associated with ASA grade or 3 or more, revised cardiac risk index of 3 or more, NYHA or 3 or more, out of hours procedures, emergency surgery and pre-existing cardiomyopathy.
  • Multi-variate logistic regression identified 3 predictors of perioperative cardiac arrest. ASA grade of ≥3 (OR 2.59, p=0.007, 95% CI 1.29 to 5.19), emergency surgery (OR 4.00, p=0.001, 95% CI 2.15 to 7.54) and pre-existing cardiomyopathy (OR 17.48, p= <0.001, 95% CI 6.18 to 51.51).
  • Age over 75 years or less than 3 years, Gender, BMI ≥30 kg m3 , and patients with known difficult airways were not identified to be at significantly altered risk of perioperative cardiac arrest.

Conclusions

  • Patients with an ASA physical status grade of ≥3, undergoing emergency surgery or with pre-existing cardiomyopathy appear to be at an increased risk of perioperative cardiac arrest in this single centre European university hospital population.
  • Incidence of paediatric cardiac arrest directly caused by anaesthesia was high (5 of 12 cardiac arrests directly related to anaesthetic procedure).

Strengths

  • Clinically relevant question addressing entire anaesthetic population.
  • Findings are in-line with previous papers addressing ASA grade and risk of anaesthesia related cardiac arrest.

Weaknesses

  • Risk factors were identified retrospectively by reviewers. NYHA classification appears to have been categorised retrospectively by investigators.
  • Strength of relationship between anaesthetic procedure and cardiac arrest categorised by authors (although independently).
  • Single centre European study which may not provide generalisable results.
  • Main outcome measure is an infrequent event, and as such small variation in number of events will greatly influence the frequency reported.

Implications

  • ASA grading, urgency of surgery and pre-operative identification of cardiomyopathy may help identify high risk cases.
  • Further studies of peri-operative cardiac arrest would be improved by establishing a consensus for the definition of anaesthesia-related and anaesthesia-contributory cardiac arrests.
  • Incidence of anaesthesia-related cardiac arrest appears to remain relatively high in the paediatric population.

Potential for impact

  • If felt to be generalisable, ASA grade ≥3, emergency surgery and cardiomyopathy may indicate patients at significantly increased risk of perioperative cardiac arrest, although this remains an infrequent event.

 

 

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