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Welsh Anaesthetic Trainees Journal Club

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

Background

  • 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

Subjects

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

Intervention

  • 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.

Outcomes

Primary:

  1. Need for vasopressors

Secondary:

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

Results

  • 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

Conclusions

  • 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

Strengths

  • 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

Weaknesses

  • 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

Background

  • 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

Subjects

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

Intervention

  • 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

Intervention:

  • 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

Outcomes

Primary

  • Number of patients with a complication

Secondary

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

Other

  • 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

 Results

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)

 Control

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

 Prehabilitation intervention

  • Mean duration 6 weeks + 12 supervised exercise session
  • PRMIARY OUTCOME
    • 50% reduction in number of patients with complications: 31% vs 62%, RR 0.5 (95% CI 0.3-0.8), p = 0.001
  • SECONDARY OUTCOMES:
    • 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)

 Conclusions

  • 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

Strengths

  • 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

Weaknesses

  • 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

Implications

  • 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

 

 

 

Journal Club: 28th March 2018

Poor performance in incremental shuttle walk and cardiopulmonary exercise testing predicts poor overall survival for patients undergoing esophago-gastric resection

European Journal of Surgical Oncology 2018 https://doi.org/10.1016/ j.ejso.2018.01.242

 Presented by: Dr T Green

Background

Patients with oesophageal and gastric cancer have a poor prognosis with an untreated five year survival at time of diagnosis of 20% and an increase to only 40% following treatment.  It can take up to one year for many patients to recover from treatment and regain their preoperative quality of life and many patients will not achieve this.  Careful preoperative assessment is essential to select those who will benefit from surgical treatment.

The Incremental Shuttle Walk Test (ISWT) and Cardiopulmonary Exercise Testing (CPET) can be used to assess the preoperative fitness of patients.  CPET results include the Anaerobic Threshold (AT) and Maximal Oxygen Consumption (VO2 Max).  This study aims to assess the correlation between ISWT and CPET with postoperative survival and postoperative pulmonary complications.

Design & Setting

Observational study of patients undergoing surgery for gastric or oesophageal cancer with or without neoadjuvant chemo-radiotherapy between 2010 and 2014 (presumably at Royal Marsden Hospital / St Mary’s Hospital, London – not stated but based on authors’ affiliations)

Data collected on preoperative clinical stage, postoperative pathological stage, postoperative respiratory complications, all-cause mortality and mortality due to disease recurrence.

Subjects

81 patients assessed through the Perioperative Enhanced Recovery Protocol between 2010 and 2014.  All patients underwent either ISWT or CPET (or both).

Intervention

Observational study – no intervention.

Outcomes

  • Assessment of the utility of the ISWT and CPET for determination of postoperative respiratory complications and mortality.
  • ISWT score of 350m or above.
  • CPET values: AT 11 or above and VO2 Max 14ml/kg/min or above.

Results

  • 73 of 81 patients (90%) had both ISWT and CPET assessment.
  • No correlation between single time point ISWT or CPET results and postoperative respiratory complications.
  • A subset of patients (45) had ISWT both before and after chemoradiotherapy and of these, those who achieved a >10% increase in score were noted to have a reduced incidence of postoperative respiratory complications (19% in those whose ISWT score improved >10% vs 45% in those whose score remained within 10% of their pre-chemoradiotherapy score or whose score reduced by >10%). This did not reach statistical significance (p = 0.08).  There was no correlation between such improvement in ISWT score and overall mortality.
  • All cause mortality and mortality due to disease recurrence correlates strongly (p < 0.001) with ISWT score ≥350m, AT ≥11 and VO2 Max ≥14 (Median survival with ISWT <350m or VO2 Max <14 was 20 months vs >5 years. Median survival with AT <11 21 months vs >5 years.)

Conclusions

ISWT assessment before and after chemotherapy is indicated and a reduction in score indicative of deconditioning, should trigger patient-specific exercise-based intervention.  CPET, being considerably more complicated and expensive, should be reserved for cases with established cardiopulmonary comorbidities.

Strengths

  • Goals and methods clearly defined.
  • Negative results reported.
  • Recognition of limitations of current study.

Weaknesses

  • Observational study therefore no case-control analysis.
  • Small sample size, especially for those undergoing ISWT before and after neoadjuvant chemoradiotherapy leading to underpowered statistical analysis.
  • The concurrent study being performed by the authors assessing the introduction of patient-specific exercise-based prehabilitation appears to have preceded the results of this study and may introduce bias into the analysis and conclusions.

Implications

ISWT may be a cheaper, less complicated method of determining cardiopulmonary fitness prior to surgery for gastric or oesophageal cancer and may be of use in guiding the multidisciplinary team in determining the best course of action for a given patient (surgery or conservative management).

Potential for impact

The use the ISWT, a cheaper, simpler assessment of cardiopulmonary fitness versus CPET is attractive as long as this can reasonably be used to guide treatment options.  The use of CPET still has its place based on the results of this study.

Journal Club: 21st March 2018

Point-of-care testing for emergency assessment of coagulation in patients treated with direct oral anticoagulants

Critical Care 2017;21:32 doi:10.1186/s13054-017-1619-z

Presented by: Dr B Eagle

Background

  • The use of direct oral anticoagulants (DOAC) is increasing, yet there is no way to point of care test coagulation in patients taking these drugs.
  • Haemochron signature is a coagulation point of care test (POCT) that is sensitive to rivaroxaban and dabigatran, although its action on apixiban is unreported.
  • This study aims to evaluate the use of haemochron in guiding emergency treatment of DOAC treated patients.

Design & Setting

  • Prospective observational single centre study based in Tubingen Germany.
  • Patients enrolled receiving first dose of apixiban, rivaroxaban or dabigatran.
  • Patients excluded with any form coagulopathy or on other anticoagulants.
  • 60 patients enrolled.
  • Samples of blood taken from each subject before DOAC intake and at intervals up to 24 hours post ingestion.
  • Bedside POCT testing using Haemochron was undertaken – PT/INR, aPTT, ACT.
  • Lab anti 10a concentrations were measured and liquid chromatography with mass spec used to determine concentrations as a gold standard.
  • Analyses used to determine whether POCT can determine concentrations considered safe for emergency surgery and for stroke thrombolysis i.e. POCT PT of 1 equates to concentration of 30ng/ml for rivaroxban – considered the safe threshold for operations.

Results

  • Correlation between POCT and apixiban concentrations were weak for PT/INR and moderate for ACT.
  • No correlation for aPTT.
  • Rivaroxaban correlation strong for PT/INR and ACT and weak for aPTT.
  • Dabigatran correlated strongly with all assays.

Conclusions

  • Hemochron POCT testing correlates with rivaroxaban and dabigatran concentrations but not apixiban concentrations.
  • POCT specific cut offs can be used to exclude rivaroxaban concentrations at the bedside with high specificity.

Strengths

  • Good sample numbers
  • Novel idea, to help with a clinically relevant problem

Weaknesses

  • Essentially a lab study – using whole blood – tests not been used to actually guide any clinical intervention
  • This study does not help to determine what the clinically relevant concentrations of these drugs are – even though it can test for arbitrarily determined levels
  • Study does not discuss how Haemochron differs in effectiveness from established POC testing such as TEG or ROTEM

Implications & Potential for Impact

  • Haemochron signature could be used to rule out relevant concentrations of rivaroxaban and dabigatran.
  • May allow concentration based cut offs for operating on patients on DOACS to be used rather than time based cut offs currently used – time based estimation may be very variable

 

 

 

Journal Club: 7th March 2018

Postoperative nausea and vomiting after oral and maxillofacial surgery: a prospective study. Dobbeleir M, De Coster J, Coucke W, Politis C.

International Journal of Oral and Maxillofacial Surgery 2018 doi:10.1016/j.ijom.2017.11.018

Presented by: Dr A Phillips

Background

  • Post-operative nausea and vomiting (PONV) is common after general anaesthesia
  • PONV leads to longer hospitalisation, higher costs, lower patient satisfaction
  • Risk scores (e.g. Apfel) exist but limited data on maxillofacial surgery (OMFS) as a risk factor for PONV
  • This study aimed to identify which types of OMFS are more related to PONV

Design & Setting

  • Single centre observational study
  • Participants categorised into bleeding risk based on type of surgery
  • PONV score calculated pre-op and anaesthetic tailored to minimise PONV
  • Anaesthesia non-standardised. Sevoflurane/desflurane/Propofol Target-controlled infusion (TCI) all used and non-standardised anti-emetic use.
  • Online questionnaire completed at day 3 post-op to determine if the patient had PONV

Subjects

  • 308 patients age between 8 to 87 years undergoing general anaesthesia for OMFS
  • Exclusion: cancer cases requiring post-operative high dependency unit care (HDU)

Intervention

  • A variety of maxillofacial surgeries from dental extractions to osteotomy

Outcomes

  • Primary outcome was self-reported post-operative nausea and vomiting questions (multiple choice answers) in the 3 days after surgery via an online questionnaire.

Results

  • 46.1% post-op nausea (PON) and 21.1% post-op vomiting (POV) overall
  • PON statistically significantly higher in the bimaxillary surgery (BIMAX)/ bilateral sagittal split osteotomy (BSSO) groups versus “other minor surgery” and dental extraction groups (P <0.05)
  • Similar pattern between POV groups but no statistical difference between BSSO and “other minor surgery” group

Conclusions

  • Maxillary surgery and BSSO procedures induced significantly more PONV than the other OMFS procedures. These could be included as a parameter in the calculation of the Apfel score.
  • Significantly less PON in anaesthesia maintained with sevoflurance vs. Propofol TCI

Strengths

  • An original study
  • Highlights limitations in pre-operative PONV scores

Weaknesses

  • Observational study
  • Small sample groups
  • Not specified whether elective/emergency surgery
  • No standardisation of anaesthetic or antiemetic use – higher PONV in Propofol TCI group is contrary to widespread evidence – suggests reverse causation
  • Blood loss hypothesised as contributory factor toward PONV – no quantification of blood loss
  • Ingestion of blood hypothesised as contributory factor toward PONV – no mention of the use throat packs
  • Retrospective questionnaires are subject to recall bias

Implications

  • Based on this study, we should consider patients undergoing BSSO/maxillary surgery to be at higher risk of PONV and alter anaesthetic practice accordingly

Potential for impact

  • I don’t think it likely that practice would change based on this article. After all, one of the implications would be to avoid TIVA in those at higher risk of PONV!
  • The article highlights the higher overall risk of PONV in more complex OMFS cases but does little to convince the reader that the surgeries themselves are independent risk factors for PONV.

March 2018

Written by: Dr T Green, CT3 Anaesthetics, Morriston Hospital, Swansea

SmartTots Update Regarding Anesthetic Neurotoxicity in the Developing Brain. Order BA, Suresh S, Evers AS.

Anesthesia & Analgesia 2018 doi: 10.1213/ANE.0000000000002833

In December 2016, the US Food and Drug Administration (FDA) issued a Drug Safety Communication about the potential for neurotoxicity from anaesthetic agents on the developing brain of young children and foetuses.  SmartTots is a public-private partnership between the International Anaesthesia Research Society and the US FDA.  SmartTots work in collaboration with researchers to investigate such potential neurotoxicity from anaesthetic drugs.

This special article provides an update to the current understanding with a brief discussion of two clinical trials partially sponsored by the SmartTots collaboration, one completed and one ongoing.  There is then a brief discussion of recent epidemiological studies, paving the way for the upcoming conclusion of the TREX trial.

The first SmartTots sponsored trial is the General Anaesthesia Compared to Spinal Anaesthesia trial.  This aims to compare scores on an Intelligence Quotient (IQ) test measured at five years of age, comparing children undergoing surgery with general anaesthesia to those receiving a regional anaesthetic technique.  The secondary outcome of performance differences at the age of two years is available and encouragingly shows performance deficit when comparing the two groups.  The primary outcome will be available later in 2018.

The second SmartTots sponsored trial was the Pediatric Anesthesia and Neurodevelopment Assessment Study, an observational cohort design with the primary outcome to assess neurocognitive performance and behavioural outcomes in children aged eight to fifteen years, who underwent hernia repair before three years of age compared to the performance of their unexposed siblings.  The results did not support an adverse effect of anaesthetic agents on the assessed parameters.  Given the short duration of anaesthesia for a hernia repair operation, these results are felt to be in keeping with preclinical data indicating the safety of short (less than two hours) exposure to anaesthetic drugs.

An epidemiological study independent of SmartTots examined the performance of children on a primary school entrance exam, finding no performance deficit in children undergoing general anaesthesia when aged less than two years compared to age matched controls.  Interestingly in contradiction to other preclinical and clinical studies, there was a small performance deficit in children aged greater than two years when undergoing general anaesthesia.

A second epidemiological study compared overall school grades and military conscription IQ tests between those undergoing general anaesthesia on at least one occasion before the age of four years.  The results were similar for one exposure to general anaesthesia and for multiple exposures, with a small reduction in school grades and military conscription IQ tests scores although no details of duration of general anaesthesia or agent used is available.

A Study to Compare the Long-term Outcomes After Two Different Anaesthetics (TREX) Trial is an ongoing trial comparing neurodevelopmental outcomes after anaesthesia for surgery with low dose sevoflurane in combination with remifentanil and dexmedetomidine versus standard sevoflurane-based anaesthesia with anaesthetic duration of at least two and a half hours.

A description of preclinical evidence for the neurotoxicity of anaesthetic agents on the developing brain is given but is covered in the summary of “Long-term neurocognitive outcomes following surgery and anaesthesia in early life.”

This article is intended as a brief update to the current evidence in the debate over the safety of general anaesthesia in young children with immature brain physiology.  It is encouraging that clinical trials have not demonstrated a significant deficit in neurocognitive or neurodevelopmental parameters following exposure of the developing brain to anaesthetic agents.  The mainstream media and tabloids were avidly reporting the potential for harm from general anaesthesia to the developing brain when the FDA Drug Safety Communication was released and the studies summarised in this update are helpful in counselling parents of young children who need to undergo anaesthesia for surgery.

Long-term neurocognitive outcomes following surgery and anaesthesia in early life. Hansen TG, Engelhard T.

Current Opinion in Anaesthesiology 2018 doi:10.1097/ACO.0000000000000577

Controversial and alarming warnings about the potential for harm to the developing brain from exposure to anaesthetic agents have been given, such as the US Food and Drug Administration Drug Safety Communication.  These have been largely based on preclinical animal studies.  This brief review assesses these preclinical studies alongside the results of some human studies.

Preclinical animal studies including nonhuman primates have indicated an association between exposure to anaesthetic agents and neuroapoptosis and abnormal synaptic development, leading to neurocognitive impairment.  The studies seem to implicate all classes of general anaesthetic agent.

In the preclinical animal studies, the anaesthetic technique is markedly different to that employed in clinical practice.  Multimodal monitoring techniques and airway management are technically difficult or impossible to implement on neonatal small animals and therefore such monitoring and management as would be standard in clinical practice was not implemented, leading to likely hypoventilation, hypoxia and hypotension.  This is reflected in the (unreported) excessively high mortality of the animal subjects.  It is widely accepted that physiological derangements such as hypoxia and hypotension can be detrimental to the central nervous system and the studies have no mechanism for excluding this as the cause of observed neurocognitive deficits.

Studies to date are unable to pick apart the likely complex interplay of the exposure to anaesthetic agents, the stress response to surgery and the effects of the underlying condition necessitating surgery.

Also reviewed are human trials examining the neurocognitive and behavioural effects of anaesthetic exposure to the immature brain.  These are discussed further in “SmartTots Update Regarding Anesthetic Neurotoxicity in the Developing Brain”.  In essence, there is no convincing evidence of a clinically significant detrimental impact of anaesthetic agent exposure on neurocognitive and behavioural outcome in later life.

Providing surgery without anaesthesia would be ethically unacceptable and therefore the risks of delaying surgery (and therefore anaesthetic exposure) needs to be balanced against the potential risks from such anaesthetic exposure.  The evidence provided so does not justify a change to current clinical practice.  We should however be prepared to be asked about this topic by concerned parents of children requiring surgery.

*These two articles follow on from articles reviewed in the journal watch of January 2017 and April 2017. This is a topic that is unlikely to disappear soon given the coverage in mainstream and tabloid media.

Cognitive decline in the middle-aged after surgery and anaesthesia: results from the Wisconsin Registry for Alzheimer’s Prevention cohort

Bratzke LC, Koscik RL, Scheming KJ et al. Anaesthesia 2018 doi:10.1111/anae.14216

Recent interest has been seen in the neurocognitive effects of surgery and anaesthesia on children and the elderly.  The middle-aged however have been assumed to be non-susceptible to such effects and Patel et al (Anaesthesia 2016 71: 1144-52) when assessing cognitive decline in the elderly following anaesthesia and surgery state “A younger cohort would be unlikely to show any effect, since very few would be cognitively impaired before surgery”.

In this study, the authors conduct a prospective longitudinal cohort study to assess the effect anaesthesia and surgery may have on neurocognitive parameters in the middle-aged with no neurocognitive deficit at baseline.  Participants were sought from the Wisconsin Registry for Alzheimer’s Prevention (WRAP).  Serial psychometric analysis was performed at baseline, five years and nine years.  Patient-reported procedures in the intervening periods between psychometric testing were explored in further detail by analysis of healthcare records (anaesthetic charts, operation notes and discharge summaries).

964 candidates were included in this study with 212 having surgery before the first cognitive assessment and 130 having surgery before the second cognitive assessment.  The mean age at baseline was 54 years.

The findings were a decline in immediate memory in participants undergoing one or more surgeries during the study with an association noted between number of surgeries, cumulative duration of anaesthesia and surgery and the American Society of Anesthesiologists (ASA) physical grade.  No difference in working memory or executive function were identified.  The decline in immediate memory, while statistically significant, is of questionable clinical importance, being sufficiently small so as to not qualify as mild cognitive impairment or dementia.

This study does exhibit limitations, some of which are recognised by the authors.  Reliance on patient reporting of relevant surgical procedures may lead to omission of some relevant procedures with subsequent skewing of the results.  The surgery, although heterogenous in nature was controlled in that intracranial procedures and those requiring cardiopulmonary bypass (both directly linked to neurocognitive changes) were excluded.  Importantly however the type of anaesthesia was heterogenous, with general anaesthesia and neuroaxial or regional techniques combined together with no subgroup analysis reported.  Retrospective analysis of the study power showed 80% power and this combined with the small effect noted, leaves the question of cognitive decline in the middle-aged after surgery and anaesthesia unanswered.

Comprehensive geriatric assessment for older people admitted to a surgical service (Review). Eager G, Taheri A, Chen S et al.

Cochrane effective practice and organisation of care group 2018 doi:10.1002/14651858.CD012485.pub2

Comprehensive Geriatric Assessment (CGA) is a multidisciplinary diagnostic process utilising medical, psychosocial and functional assessment to develop an individualised management plan for older people.  Members of the multidisciplinary team include geriatric assessment trained physicians, nursing staff, physiotherapists and occupational therapists.  Previous research has shown it to be effective in both internal medicine and orthogeriatric patients.

Given the ageing population and the estimate that more than fifty percent of surgery is performed on those aged over sixty five years, mechanisms to improve overall care and outcomes from surgery in older people is of extreme importance.

This Cochrane systematic review aims to assess the use of CGA in the surgical population.  The primary outcomes were mortality and discharge to an increased level of care compared to baseline.  Secondary outcomes were length of stay, readmission rate, postoperative complications and total cost of care.  Subgroup analysis was performed to assess:

  • Orthopaedic vs other surgical specialties
  • Timing of CGA (preoperative vs postoperative)
  • Emergency vs elective surgery

Eight randomised trials were included in the systematic review, representing 1843 patients overall.  Of the eight trials, seven were specific to hip fractures and one was specific for elective oncology surgery.

Primary outcome results are reported as orthopaedic surgery alone or combined with the solid tumour surgery trial.  Mortality was reduced in hip fracture surgery but this was largely mitigated when elective oncology surgery was included.  Discharge to an increased level of care was reduced in patients undergoing surgery for hip fractures however inclusion of elective oncology surgery patients resulted in little to no effect on length of stay.

Secondary outcome results showed marked heterogeneity for length of stay but an overall small reduction was found.  No change in the rate of readmission was found but only two orthopaedic trials and one elective oncology surgery trial reported this measure, with relatively small numbers of patients overall.  Cost analysis was limited as only a single study reported this.  There appears to be a modest reduction in total cost at one year follow-up (€59,486 standard care vs €54,332 CGA).  Postoperative complications were not amenable to systematic review due to differing ways of reporting these.

Subgroup analysis is reported above for orthopaedic vs other surgical specialties.  Post-operative CGA was found to probably reduce mortality and length of stay compared to standard care but the confidence interval crosses 1.  No assessment of emergency vs elective surgery was made.

Overall, this systematic review provides evidence that CGA provides reductions in mortality and length of stay in hip fracture patients but is unable to generalise these findings to other orthopaedic procedures or non-orthopaedic surgery due to the paucity of studies.  As such, this systematic review is unable to answer the intended question – does Comprehensive Geriatric Assessment improve the outcome after admission to surgical services?  Further research is needed to extend the variety of trials in non-hip fracture orthopaedic surgery and non-orthopaedic surgery.

Preoperative versus postoperative ultrasound-guided rectus sheath block for improving pain, sleep quality and cytokine levels in patients with open midline incisions undergoing transabdominal gynaecological surgery: a randomized-controlled trial. Feng Jin, Zhe Li, Wen-fei Tan, Hong Ma, Xiao-qian Li and Huang-wei Lu.

BMC Anesthesiology 2018, 18:19 doi: 10.1186/s12871-018-0485-9

Rectus Sheath Block (RSB) is a commonly used, effective and safe analgesic technique for midline incisions for surgical procedures.  It is commonly performed preoperatively and has been shown to reduce the intraoperative anaesthetic requirements.  It has been suggested however that improved results may be evident with postoperative RSB as this will prolong the duration of action of the local anaesthetic, with improved analgesia.

This study aimed to examine preoperative versus postoperative RSB with specific regards to time to first use of patient-controlled analgesia (PCA) pump, total dose of opioid analgesic required using the PCA pump, levels of inflammatory cytokines (Interleukin-6 / IL-6, Interleukin-1β / IL-1β, Interferon-γ / IFN-γ, Tumour Necrosis Factor-α / TNF-α) measured by serial venepuncture and sleep quality assessed using Bispectral Index (BIS) monitoring (elevated IL-6 has been associated with reduced sleep quality).  Several studies have been performed validating the use of BIS monitoring on depth of natural sleep (e.g. Giménez et al 2017, J Clin Monit Comput.  Doi 10.1007/s10877-015-9805-5)

Sixty four patients undergoing elective non-cancer open abdominal gynaecological surgery were randomised to either receiving preoperative RSB with 0.5% ropivacaine followed by postoperative RSB with saline or the reverse.  The RSB was performed by a single, experienced anaesthetist and the overall anaesthetic technique was standardised.

The findings showed no significant difference between the visual analogue pain scale rating between the two groups, the time to first use of the PCA pump nor the total opioid requirement at twenty four or forty eight hours postoperatively.  Markers of surgical stress in the form of proinflammatory cytokines were consistently and significantly reduced and BIS data showed a statistically significant improvement in time spent at stage N2 and N3 sleep for those receiving preoperative RSB.

Statistical analysis found that thirty two patients would be needed in each arm for a power of 80% however due to problems with BIS monitoring in two patients, the preoperative RSB group ultimately had thirty patients (thirty two in the postoperative RSB group), leaving the study underpowered overall.

This study is a neat demonstration of the benefit to using preoperative rectus sheath block in open non-cancer gynaecological surgery.  With small numbers leaving the study underpowered and the inclusion of only one type of surgery, further work is needed.

Effective dose of dexmedetomidine as an adjuvant sedative to peripheral nerve blockade in elderly patients. Wang C, Zhang H, Fu Q.

Acta Anaesthesiologica Scandinavia 2018 doi:10.1111/aas.13087

Dexmedetomidine is a relatively new drug with an increasing repertoire for use.  This study assesses the dose required for sedation following peripheral nerve blockade for total knee arthroplasty in older patients.

Forty two patients aged 65 – 85 years were included in the study (two patients were excluded following failure of peripheral nerve blockade and one was excluded due to vomiting affecting the assessment of sedation).  The patients were stratified into two groups – “young-old” aged 65 -74 years and “middle-old” aged 75 – 85 years.  A single calculated dose of dexmedetomidine was administered as a ten minute infusion and the level of sedation assessed using the Observer’s Assessment of Alertness / Sedation Scale.  This was correlated with Bispectral Index (BIS) value alongside usual monitoring parameters.

The dose of dexmedetomidine was adjusted for serial patients based on the previous patient’s reposnse (the Dixon up-down method).  From these data, Effective Dose 50% (ED50) and Effective Dose 95% (ED95) can be determined.

The results showed:

  Young-old Middle-old
ED50 (mcg/kg) 0.57 (0.47 – 0.65) 0.38 (0.28 – 0.46)
ED95 (mcg/kg) 0.76 (0.67 – 1.08) 0.57 (0.48 – 0.89)
BIS50 86 (81 – 91) 85 (84 – 87)
BIS90 72 (53 – 78) 73 (69 – 76)

 

The ED50 showed increased sensitivity with advancing age, in-keeping with previous studies and the BIS values showed no statistical difference between the age groups.  No patient experienced oxygen desaturation and haemodynamic monitoring showed a modest reduction in heart rate and systolic blood pressure without adverse effects.

Limitations of the study include the use of midazolam (1mg) and fentanyl (50 micrograms) prior to nerve block as these agents will confound the sedative effect of dexmedetomidine.  The study is limited to a single surgical procedure and anaesthetic technique and the data from this study are therefore not generalisable to other operations or anaesthetic techniques.  The number of patients enrolled is quite small but this study serves an important role for setting a benchmark for single dose dexmedetomidine as a sedative adjunct to peripheral nerve blockade.

Journal Club: 28th February 2018

Evaluation of reliability of MYZONE MZ-3 Heart Rate Monitor: A study for the Future of Telephysiotherapy for Preoperative Prehabilitation in Cancer Patients.

TELEMEDICINE and e-HEALTH 2017;23(4):1-5 doi:10.1089/tmj.2016.0138

Presented by: Dr C Francis

Background

Pre-operative optimisation programs seek to implement a series of interventions to improve and enhance recovery after major surgery. An important aspect of this is the use of exercise programs. The Authors of this paper suggest a major barrier to successful completion of these programs could be inaccessibility of in-hospital supervised exercise programs. There is an increasing abundance of wearable technology, however the accuracy and reliability of commercially available Heart Rate monitors is variable.

Design & Setting

Small, prospective, pilot experiment at single centre in Australia. Small sample (n=7) of young, healthy volunteers without significant medical history and in normal sinus rhythm recruited. Asked to perform increasing intensity effort on exercise bike wearing the MYZONE MZ-3 Heart rate monitor and a clinical 3 lead ECG system. Paired HR measurements to be taken and compared statistically using a Bland Altman plot

Subjects

Seven young physically active, healthy individuals in normal sinus rhythm (mean age 29.7 years; 5 female, 2 male)

Intervention

Asked to complete an exercise on static bike of increasing intensity whilst wearing both clinical 3 lead ECG and MYZONE MZ-3 HR monitor.

Outcomes

1,983 data points collected. Of which 55 data points unpaired as loss of contact with MYZONE MZ-3 HR Monitor. Only paired data sets included. Significantly 5 of the 7 participants had their collected data received out of sync, reported as being due to a failure to manually synchronise time on both MYZONE MZ-3 HR and ECG monitors pre test. Authors included this data after retrospective correction of data by aligning out of sync data, moving the sample to the left by 20 seconds. The authors feel this adjustment of data unlikely to cause any clinically significant effects on results.

Results

Using a Bland-Altman plot able to demonstrate a bias of 0.4bpm, and adjusted 95% limits of agreement (95% LOA) to be -4.5 to +5.3 bpm. And a percentage error [95%LOA/mean HR] of 3.6%

Conclusions

MYZONE MZ-3 has an acceptable level of reliability for use in healthy volunteers performing exercise across a wide range of HR. Further studies using a similar methodology are required to validate the use in patients presenting for cancer surgery.

Strengths

  • Prospective study
  • Appropriate use of statistical analysis to assess reliability and precision of HR monitor.

Weaknesses

  • This study had a very small sample size, of healthy, young volunteers. Therefore, this cannot be extrapolated to those awaiting cancer surgery.
  • None of the participants were noted to have any features which may have produced inaccuracy such as arrythmias, obesity, tremor, pacemakers.
  • A static bike was used and so there was minimal movement artifact.
  • 55 data sets were not paired due to the loss of contact with HR monitor and are not included in reliability figures.
  • Perhaps most significantly there is retrospective alteration of the data collected from 5 out of the 7 participants. Whilst the authors claim this is unlikely to have caused significant effects to the results I fail to see how an experiment with aims of assessing precision and accuracy of a piece of equipment can be deemed safe when 5/7 of data sources have been altered retrospectively.
  •  In addition, there was no structured exercise protocol used and no examination of the cost benefit of the intervention.

Implications

  • Limited at present.
  • Could be deemed a starting point for a project requiring significant further examination.

Potential for impact

Increasing numbers of wearable technologies are available and being used in the community. There is much competition between devices and price points are changing dramatically as with most tech products. The use of these products could be of great use in prehabilitation of pre-operative patients. There is much scope for further investigation and cost benefit analysis of this and similar products.

Journal Club: 21st February 2018

Intraoperative Infusion of Dexmedetomidine for Prevention of Postoperative Delirium and Cognitive Dysfunction in Elderly Patients Undergoing Major Elective Noncardiac Surgery: A Randomized Clinical Trial.

JAMA Surgery. Published online June 2017. doi:10.1001/jamasurg.2017.1505

Presented by: Dr B Morris

Background

This study aims to tackle the issue of high rates of post operative delirium (POD) and post operative cognitive dysfunction (POCD) in elderly patients. There is thought to be a high incidence of POD (10-60%) and this is also thought to contribute to POCD, a more permanent alteration of mental state. Both these conditions are associated with disadvantageous features such as increased perioperative morbidity, increased length of stay and ultimately decreased life expectancy and quality of life, so it is a significant problem. The authors aimed to evaluate specifically the perioperative use of an infusion of Dexmedetomidate as this has been shown to improve delirium and cognitive dysfunction in ICU patients.

Design & Setting

A double-blind, randomized, parallel group placebo-controlled trial in 10 centres across the USA over 6 years (2008 – 2014).

Subjects

Of 404 patients who were initially randomized, 390 made it through to be included in the results of the trial. These were patients selected by the following criteria: Age over 68 (adjusted from 70 in the interest of gaining more numbers), undergoing major (planned 2 day admission) elective non-cardiac surgery under GA. There was a long list of exclusory criteria, including surgical, anaesthetic and patient factors such as intracranial/emergency surgery, planned post operative intubation, life limiting conditions, preexisting cognitive conditions and ASA IV/V.

Intervention

An infusion of 0.5mcg.kg-1.hr-1 of Dexmedetomidine commenced in the anaesthetic room and continued until 2 hours into recovery, vs placebo of saline.

Outcomes

Primary: Presence of delirium whilst hospitalised or until day 5 post operatively.

Secondary: Post operative cognitive decline up to 6 months post operatively.

Results

The trial was stopped early due to futility and failure to find any difference between the two groups.

Primary outcome:

23 patients from the Dexmedetomidine group (12.2%) and 23 patients from the control group (11.4%) developed post operative delirium (risk ratio, 1.06; 95% CI, 0.79-1.41; P = .77). Interestingly they did isolate some other factors that made POD more likely – namely increased length of surgery, baseline mild cognitive impairment, lower number of educational years and type of surgery, general surgery being the least likely to be associated with POD.

Secondary outcome:

There was found to be no statistically significant difference between the two groups in POCD at either 3 or 6 months.

Unintended adverse events:

Similarly distributed between the two groups, with more bradycardia with the Dexmedetomidine group and slightly more infections, although the overall number of infections was low.

Conclusions

This study contrasted with other work on administration of dexmedetomidine in the postoperative setting of 1 or more days in cardiac and non-cardiac surgical patients, which has shown an improvement in POD.

This study did show some correlation between other factors such as educational level and baseline mild cognitive impairment and POD.

Encouragingly, there was little evidence of POCD in either group, perhaps indicating that although Dexmedetomidine is not beneficial, these patients in general are not at high risk for significant POCD anyway.

Strengths and Weaknesses

The exclusion of so many patients did allow for a more robust scientific analysis of Dexmedetomidine and its effects, as the two groups being compared were homogeneous, however this did limit the study’s usefulness in real terms as it may be in many of these excluded patients interests to have POD decreased, more so than the ‘fitter’ population studied.

Whilst absolute presence of delirium was measured, a weakness of the study is that the number of episodes, severity and consequences i.e. length of stay, etc. were not.

Implications

Basically, based on this study, we should not endeavour to provide intraoperative Dexmedetomidine infusions to elderly patients undergoing major non cardiac surgery in an attempt to ameliorate POD/POCD.

Potential for impact

This is a useful piece of research in the full context of Dexmedetomidine and POD, but needs to be taken into consideration with all of the other work done in the surrounding areas of other types of surgeries, other populations and prolonged administration post operatively.

Further research should be directed at the higher risk groups that were excluded from this study, and more far-reaching measures such as improvement in patient outcomes (both clinically objective and subjective), length of stay, financial efiiciency etc. It is also still perfectly reasonable to consider providing post operative Dexmeditomidine infusions to high risk patients in HDU/ICU environments in the absence of deleterious factors.

Journal Club: 6th February 2018

Effect of Individualized vs Standard Blood Pressure Management Strategies on Postoperative Organ Dysfunction Among High-Risk Patients Undergoing Major Surgery A Randomized Clinical Trial. 

The Journal of the American Medical Association. 2017;318(14):1346–1357 doi:10.1001/jama.2017.14172

Presented by: Dr J Lloyd

Background

Perioperative hypotension is known to be related to post operative organ dysfunction, in particular the heart, lungs, and kidneys.

Patients at high-risk of post operative organ dysfunction are also at an increased risk of mortality.

Hypertension is an increasingly common comorbidity, especially in the elderly population, and it alters the autoregulatory capacity of their brain and kidneys leaving them more vulnerable to ischaemia during an episode of hypotension than organs of normotensive patients. It is thus hypothesised that maintaining a higher systolic blood pressure during surgery, in high risk patients with hypertension, will reduce the risk of post operative organ dysfunction.

Guidelines for critical care have suggested altering haemodynamic targets to premorbid levels in hypertensive patients, but there is no good evidence for the same advice in the operating theatre.

This study aims to determine whether adjusted intraoperative haemodynamic targets in hypertensive patients can reduce the incidence of post operative organ dysfunction, and mortality

Design & Setting

A multi-centre, stratified, parallel control group randomised clinical trial conducted across 9 hospitals in France

Subjects

Patients over 50, with an ASA classification of II or greater, undergoing surgery with an expected duration of over 2 hours, and with an acute kidney injury risk index of III or higher (see figure below)

JC 6th Feb figure

Figure from: KheterpalS,TremperKK,HeungM,etal. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set. Anesthesiology. 2009;110(3):505-515.

Intervention

The patients reference blood pressure was measured preoperatively, and then the two arms of the study were protocolled as follows:

  • Experimental group – a 2.5mg in 250ml noradrenaline infusion was administered peripherally to maintain a systolic blood pressure within 10% of the reference pressure.
  • Control group – 6mg boluses of ephedrine (up to a maximum of 60mg before the use of rescue noradrenaline was permitted) were used to treat any drops in systolic BP below 80mmHg or any more than 40% below the reference pressure.

Other aspects of care were standardised such as:

  • Measurement of BP through a radial arterial line
  • Anaesthetic induction with the use of propofol 2-3 mg/kg, sufentanil 0.2 μg/kg and cis-atracurium 0.15 mg/kg. Inhaled anesthetics used for maintenance of general anesthesia, to a target bispectral index between 40 and 60, in addition to intravenous perfusion of sufentanil at 0.1 to 0.2 μg/kg per hour.
  • Mechanical ventilation with the use of a tidal volume between 8 and 10 ml/kg predicted body weight, with a positive end-expiratory pressure between 5 and 10 cmH2O, an inspired oxygen fraction (FIO2) to maintain oxygen saturation ≥95% and the respiratory rate adjusted to maintain end-tidal carbon dioxide concentration between 30-35 mmHg.
  • Blood transfusion to maintain hemoglobin level at greater than 10 g/dl.
  • Core temperature maintained at 37°C.

Outcomes

Primary outcome is a composite measure that includes both meeting the SIRS criteria, as well as demonstrating major organ dysfunction from either the cardiovascular, respiratory, renal, neurological, or coagulation systems within 7 days of the operation.

Secondary outcomes included

  • Intraoperative blood pressure variability, blood loss volume, transfusion requirement, fluid requirements, and rescue vasopressor therapy, as well as incidence of either hypotension, hypertension, or bradycardia
  • Post operative urine output, RIFLE score, requirement for renal replacement, SOFA score, duration of ICU and hospital stay, as well as a wide range of specified postoperative complications within 30 days

Results

The primary outcome event incidence was 38.1% in the treatment group and 51.7% in the control group, this gave an adjusted relative risk of 0.73 with 95% CI of 0.56 to 0.94; P = .02

Of the secondary outcomes:

  • Renal dysfunction occurred in 32.7% in the treatment group Vs 49% in the control group (adjusted relative risk 0.70 with 95% CI of 0.53 to 0.92; P = .01)
  • Altered neurological function occurred in 5.4% of the treatment group Vs 15.9% of the control group (adjusted relative risk, 0.34; 95% CI, 0.16 to 0.75; P = .007)

Conclusions

Individualised targeting of systolic blood pressure in high risk patients reduces the risk of both post operative renal and neurological dysfunction

Strengths

  • Adequately powered, well designed randomised control study, with clear inter group standardisation of care
  • A clinically relevant question

Weaknesses

  • The two regimes use two different vasopressors to attain their haemodynamic goals, so it is possible that some of the difference in outcomes could be from a pharmacological rather than haemodynamic difference.
  • Reference values for preoperative blood pressure values may not always be available in clinical practice for example with emergency surgery.
  • Necessary lack of intervention blinding for the anaesthetists delivering care
  • HES boluses to achieve maximal cardiac index is no longer standard practice, although it was the same protocol in both groups
  • Large numbers of patients were excluded based on their risk score for post operative renal impairment, which means we cannot extrapolate the results to answer the question about how this majority of patients should be treated

Implications

  • In cases of expected prolonged surgery, where patients are known to be at risk of post operative renal dysfunction, maintaining systolic pressures of within 10% of their baseline will decrease the risk of post operative renal and neurological dysfunction.
  • It also demonstrates the safety of peripheral dilute noradrenaline, as no adverse outcomes were reported

Potential for impact

Widespread application of the conclusions has the potential to reduce morbidity in a high risk patient group

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