Welsh Anaesthetic Trainees Journal Club


June 2018

What is the ‘safe’ timing of surgery after an ischaemic stroke?

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


  • 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.


  • 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.


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


  • 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.


  • 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. 


  • 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.


  • 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.


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.

Frailty and postoperative outcomes

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


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)


  • 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.


This was an observational study


Complication rates after inpatient surgery


Increasing frailty increases your rate of complications


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


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


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


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.

Home fitness monitors versus CPET……do they compare?

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


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.



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.


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.


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.


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.


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.



  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!).


  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.


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.

Restricted or liberal IV fluids. Which is better for major abdominal surgery?

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


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.


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.)


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.


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.


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.


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.


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.


  • 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.


  • 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


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.


  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.

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