Welsh Anaesthetic Trainees Journal Club


April 2018

Journal Club: 18th April 2018

Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study

British Journal of Anaesthesia 2018;120(2):274-283

Presented by: Dr I Rees


  • Normal saline 0.9% amongst most commonly used crystalloid for fluid therapy
  • However normal saline not ‘normal’
    • Sodium and chloride concentrations 154mmol/l
    • Risk of hyperchloraemic metabolic acidosis and reduced anion gap
    • Linked to increased risk of renal dysfunction, transfusion and mortality in patients undergoing abdominal surgery
  • Balanced crystalloids contain metabolisable anions (lactate or acetate)
    • Maintain electrolyte stability
    • Less associated with metabolic acidosis
    • Metabolised to bicarbonate
  • Recent study in same centre demonstrated patients undergoing cadaveric renal transplantation required significantly less catecholamine support if receiving balanced crystalloid, compared to the group receiving normal saline
  • Authors hypothesised that patients undergoing major surgery might require less vasopressor support if they received a balanced crystalloid, as opposed to normal saline perioperatively

Design & Setting

  • Single-centre (Department of Anaesthesiology of the Medical University of Vienna, Austria)
  • Prospective double-blinded randomised controlled study of patients undergoing elective major abdominal surgery
  • Patients and anaesthetists blinded
  • Ethics approved
  • Sample size calculated (based on previous transplantation study) – 120 patients per group (240 total) to give α 5% and 80% power


Inclusion criteria:

  1. Adult, non-pregnant patients
  2. Undergoing elective major abdominal surgery (any general, gynaecological or urological procedure requiring laparotomy)

Exclusion criteria:

  1. LV ejection fraction <30%
  2. Renal dysfunction (GFR <30ml/min) and severe liver disease
  3. Chronic inflammatory diseases requiring long-term steroids
  4. Pre-operative sepsis or critical care patients
  5. Contraindications to oesophageal doppler
  6. Intraoperative epidural analgesia


  • Patients randomised on day of surgery to receive either normal saline or a chloride-reduced acetate-buffered balanced crystalloid (Elomel Isoton)
  • No pre-operative fluid infusion
  • Blinded fluids given to anaesthetist before induction of anaesthesia
  • Standardised anaesthetic:
    • Standardised induction (propofol 2-3mg/kg, rocuronium 0.6mg/kg and fentanyl 2-3mcg/kg)
    • Standard monitoring including arterial line and CVP + depth of anaesthesia monitoring (Narcotrend), train-of-four ulnar montoring and oesophageal doppler (CardioQ)
    • Sevoflurane administration according to Narcotrend; FiO2and fentanyl boluses according to clinical requirement; Rocuronium to maintain one or two twitches on TOF
    • Ventilation to maintain end-tidal CO2 near 35mmHg (~4.6kPa) – tidal volume 8-10ml/kg (LBW), peak pressure <30mmHg (~40cmH2O) and PEEP of 5mmHg (~7cmH2O) or higher according to patient need.
    • Temperature >36oC using forced air warmer and hourly arterial blood gases
    • Fluid maintenance 2ml/kg/hr (IBW as per Robinson’s formula) increased to 5ml/kg/hr on exposure of viscera
  • Target MAP according to pre-operative blood pressure the day before surgery:
Pre-operative Blood Pressure (mmHg) Intraoperative Target MAP (mmHg)
Hypotensive SBP <120 60
Normotensive SBP 120-139 / DBP 80-89 70
Hypertensive SBP >140 / DBP >90 80
  • If MAP fell, standardised protocol followed:
    • SV responsiveness assessed using 250ml fluid challenge
    • If >10% increase in SV but MAP still below desired value, further 250ml boluses until SV increase <10% or target MAP achieved
    • If target MAP still not achieved and SV ‘unresponsive’, phenylephrine 0.1-0.2mcg bolus given (maximum 0.8mcg/hr)
    • If still insufficient, noradrenaline infusion started at 0.01-0.02 mcg/kg/min and titrated to desired MAP by increments of 0.05-0.1mcg/kg
    • If SV fell by >10% of the value following the last fluid challenge, a further 250ml was given
    • Noradrenaline titrated down or stopped if fluid challenges sufficient in maintaining MAP
  • Exit criteria: pH below 7.2, bicarbonate below 14mmol/l, base excess below -10mmol/l or response to catecholamines insufficient – fluid changed to balanced crystalloid and study was terminated.



  1. Need for vasopressors


  1. Total dose of catecholamines
  2. Total perioperative fluid
  3. Unplanned intensive care admissions


  • Terminated early for safety reasons (hyperchloraemic metabolic acidosis) after discussion with study safety board and local authority
  • Only 60 of the total planned 240 were studied (30 in each group)
  • More patients required vasopressors in the normal saline group than the balanced crystalloid (97% vs67% respectively,p=0.033)
  • Median weight and duration-adjusted dose of norepinephrine were 0.11(0.00-0.45)mcg/kg/min in the normal saline group compared with 0.00mcg/kg/min in the balanced crystalloid group (p=0.003)
  • No difference between groups in total perioperative fluid and unplanned intensive care admissions
  • Cox regression showed need for vasopressors related to high volume of administered fluid, normal saline resuscitation and lower MAP


  • Study suggests that patients undergoing major abdominal surgery with normal saline fluid therapy have a significantly larger vasopressor requirement than those receiving a more physiological crystalloid.
  • Hyperchloraemia with or without acidosis may be a direct trigger for unfavourable cardiovascular effects – leads to increased nitric oxide, as seen in rats


  • Focused question asked
  • Hypothesis based on previous study
  • Prospective double-blinded RCT
  • Patient groups comparable
  • Appropriate inclusion and exclusion criteria
  • Extremely standardised protocol
  • Appropriate statistical analysis i.e. Mann-Whitney U Test for quantitative, non-parametric analysis of 2 unpaired groups


  • Terminated due to patient safety
  • Underpowered (67%) for primary outcome due to low numbers – power 90% for secondary outcomes
  • Single-centre
  • Protocol resulted in large amounts of intraoperative fluid infusion (median 3427ml of normal saline and 3144 of the balanced crystalloid)
  • No mention of blood products
  • No epidural or intrathecal block
  • Is it an important clinical question?

Implications/Potential for impact

  • Is our practice likely to change following this study?
  • Inference that normal saline may cause detrimental cardiovascular effects due to hyperchloraemic acidosis (leading to increased nitric oxide, as seen in rats) is interesting
  • Vast majority of anaesthetists likely to use a balanced crystalloid e.g Hartmann’s solution, rather than normal saline for elective adult surgery (save for a few circumstances e.g. liver failure etc) as it is more ‘physiological’ – why cause further stress during the stress response?

Following this underpowered study that put patients in harm’s way, I will do as the authors suggest i.e. exactly what I’ve been doing this entire time.

Journal Club: 11th April 2018

Personalised Prehabilitation in High-risk Patients Undergoing Elective Major Abdominal Surgery. A Randomised Blinded Controlled Trial.

 Annals of Surgery 2018;267(1):50-56 doi:10.1097/SLA.0000000000002293

Presented by: Rebeca Harris ST4


  • Major abdominal surgery is associated with a high rate of postoperative complications, particularly in elderly patients with multiple comorbidities.
  • Aerobic capacity determines postoperative functional reserve, which is negatively associated with postoperative morbidity and mortality.
  • Prehabilitation exercise programmes are postulated to improve aerobic capacity, and thereby reduce postoperative complications.
  • Previous studies have shown a bias towards low-risk patients, and lack of evidence on postoperative clinical outcomes.
  • Prehabilitation is defined as a preparatory intervention aiming to increase aerobic capacity. Methods include supervised endurance exercise training and the promotion of physical activity.

Design & Setting

  • Single centre: Hospital Clinic de Barcelona
  • Patients were blindly randomized
  • Collaborating anaesthetists and surgeons were blinded to patient’s allocation
  • Ethics approved
  • Sample size prospectively powered (as standard, accepting risks of: α 0.05 and β 0.2), based on:
    • the reduction rate of patients with postoperative complications as the main outcome
    • considering the local colorectal complication rate (30%), and
    • anticipating up to 20% drop out
    • Intention-to-treat analysis


High risk patients for elective major abdominal surgery

Inclusion criteria:

  • Elective major abdominal surgery
  • High risk defined by all of the following:
    • Age > 70 and/or ASA III/IV
    • Duke Activity Status Index Score < 46
    • Preop schedule allowed at least 4 weeks for the prehabilitation intervention

Exclusion criteria:

  • Non-elective surgery
  • Unstable cardiorespiratory disease
  • Locomotor limitations precluding exercise training
  • Cognitive deterioration impeding adherence to the programme


  • Baseline assessment within 1 week of preoperative assessment
  • Reassessment 1 week before surgery

Standard care:

  • Physical activity, nutritional and smoking cessation advice
  • IV iron if indicated for anaemia
  • Nutritional intervention if high-risk for malnutrition


  • Personalised prehabilitation programme based on health and social circumstances
  • Mostly community based
  • 3 major aspects
    • Motivational interview to assess adherence profile. Tailored physical activity programme then co-designed with the patient
    • Personalised daily physical activity programme
      • Pedometer to measure steps, then feedback and optimization
    • Supervised high intensity endurance exercise programme
      • 1-3 per week
      • Exercise bike interval training, tailored to increase intensity over time, based on work rate
      • Pulse oximetry and self-perceived exertion measured



  • Number of patients with a complication


  • Number and severity of postoperative complications
  • Hospital and ICU length of stay


  • Endurance time
  • Distance covered in 6 minute walking test
  • Physical activity (by validated patient survey)
  • Self perceived health status (by validated patient survey)
  • Psychological status (by HADS patient survey)
  • Pulmonary function tests
  • Cardiorespiratory exercise tests


Baseline characteristics

  • 209 assessed over 3 years – 144 eligible and randomised (> 70 per group, as per power analysis minimum)
  • Comparable patient characteristics between groups
  • 19 did not receive operation, so excluded mid-trial
  • Control: 1 unable to perform exercise testing, 6 abandoned
  • Intervention: 4 unable to perform exercise testing, 4 abandoned
  • 56 (Control) and 54 (Intervention) completed trial (< 70 per group, and > 20% dropout rate, thus underpowered)


  • No change in baseline characteristics at start vs 1 week pre-surgery

 Prehabilitation intervention

  • Mean duration 6 weeks + 12 supervised exercise session
    • 50% reduction in number of patients with complications: 31% vs 62%, RR 0.5 (95% CI 0.3-0.8), p = 0.001
    • Increasein Endurance Time (135%, p < 0.001)
    • Increasein Physical Activity Index (37 points, p< 0.001)
    • No significant difference in intraoperative parameters, but trend towards lower requirement of vasoactive drugs (p=0.053)
    • Lower mean number of complications per patient : Cardiovascular(p = 0.03, RR 0.1, 95% CI 0.1-1.0), Infection of uncertain source (p = 0.013, RR not possible), Paralytic ileus (p = 0.001, RR not possible)
    • In patients with complications, intervention reducedrisk of having more than one complication (RR 0.6, but 95% CI 0.3-1.1), but no effect on severity of complications.
    • Reduced length of ICU stay (3 vs 12 days, p = 0.046)


  • High intensity endurance exercise training is feasible and safe in elderly and/or multimorbid candidates for major abdominal surgery
  • Prehabilitation enhanced clinical outcomes in high-risk candidates for elective major abdominal surgery, which can be explained by the increase in aerobic capacity
  1. Reduced complication rate
  2. Prevents > 1 complication
  3. Reduced ICU length of stay


  • Randomised blinded controlled trial
  • High risk patient group selected, reflecting patient population
  • Initially adequately powered
  • Performed within realistic preoperative timeframe for urgent surgery
  • Highly personalised, patient-centred prehabilitation programme. Well detailed for reproducibility
  • Interesting secondary outcomes, validated tools used
  • Appropriate statistical analysis employed
  • Number of patients abandoning intervention arm < control, thus patient engagement good


  • Single centre
  • Blinding of clinicians following interaction with patients may have been difficult
  • Underpowered following dropouts – still able to demonstrate statistically significant difference in primary outcome, however may have ‘missed’ other significant differences in secondary outcomes
  • ? Blinding of exercise tester
  • Primary outcome extremely broad – ‘any complications’ postoperatively. Not specific, and therefore clinical significance and importance of question reduced.
  • Survival and functional recovery not assessed
  • Underpowered to assess effect on specific and important post operative complications
  • Did not demonstrate a difference in the severity of postoperative complications
  • Claims significant reduction in CV complications and the number of patients having > 1 complication, but:
    • Reduction in CV complications 95% CI 0.1-1, wide and includes ‘no effect’
    • Reduction in number of patients having more than 1 complication 95% CI 0.3-1.1, wide and includes ‘no effect’
  • Endurance time rather than familiar, objective CPEX data e.g. Anabolic threshold, formed basis of measure of aerobic capacity
  • Intensive, highly tailored programme
    • ? Sustainability on larger scale
    • No cost analysis


  • Prehabilitation in elderly, multimorbid patients appears to be feasible, safe and ‘acceptable’ to patients
  • Prehabilitation can increase preoperative exercise endurance in high risk patients
  • Postoperative complication rates can be reduced by this strategy
  • However, larger trials are required to further characterise and assess the clinical significance of postoperative complication benefits, and to determine the effect on functional recovery and survival

Potential for impact

  • Important step towards assessing the potential benefits and characterising the design of prehabilitation exercise programmes in high risk patients undergoing high risk elective surgery
  • Important and exciting emerging field of research with potential for significantly improving patient outcomes




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