Tuesday, 18 August 2015

Response of bispectral index to neuromuscular block in awake volunteers. BJA July 2015.

This is an Australian study out of Cairns that harks back to earlier days of anaesthetic research where advances were made by anaesthetists experimenting on each other.

In 2003 a study was published in Anaesthesia and Analgesia by Messner et al demonstrating that the BIS was dropped significantly following administration of succinylcholine in awake volunteers. The explanation for this was unclear but it was postulated that EMG was affecting the BIS in a way that the monitor was not compensating for. The study was conducted using an early form of BIS monitor and newer models have attempted to address this problem. Subsequent versions have included an additional electrode designed to identify signal contents related to muscle activity and the software now generates an indicator of EMG. The contribution of the EMG to the BIS score in these newer monitors is known only to the manufacturers. It is unclear if it’s role relates simply to assessing signal quality or if it contributes directly to the score its self.

This study published in July’s BJA replicates Messner’s assessment of the level of awareness monitor using these newer BIS models. Inclusion criteria were that the subject was an Anaesthetist, was ASA 1 or 2, 25-60 year old, no GORD, no signs of difficult airway, BMI <25, no anxiety disorder. Each subject was paralysed initially with 1.5mg/kg sux and BIS was monitored until return of muscle activity. At a later date the experiment was repeated with 0.7mg/kg rocuronium followed by reversal with sugammadex at 20 minutes. Consciousness was confirmed with an isolated forearm technique. Subjects were asked to conduct math problems answering with their hands, and remember facts from stories in order to demonstrate full awareness. A rescue dose of propofol would be administered if significant distress was demonstrated.

11 anaesthetists were recruited for the study. BIS was monitored for 12 minutes following sux and 20 minutes following rocuronium. Following administration of muscle relaxant all patients demonstrated a two-stage drop in their BIS during the first few minutes of paralysis that was maintained until the return of muscle activity. Most subjects spent a significant period of the experiment with a BIS less than 70 (rough average of 15-40% of the observational period) whilst some subjects recorded a BIS < 60 for 10-20% of the time.

This result questions the reliability of BIS as a measure of awareness in the paralysed patient.

Important points:
  • The original BIS algorithms were generated from a database of EEGs recorded in anaesthetised patients who had not received muscle relaxants
  • The dataset used to develop BIS would not have included an awake and paralysed patient and it may be insufficiently designed to identify this clinical scenario
  • Both BIS and Entropy monitors include EMG activity in the synthesis of a level of awareness value, but it is not known how the EMG contributes to these scores by anyone except the manufacturers.
  • In this study, patients were most commonly found to be in the range of 60-80 when they were paralysed but fully conscious. The manufacturers have suggested this level of anaesthesia is appropriate for the end of surgery. With the introduction of sugamadex many anaesthetists are maintaining deeper paralysis upto the end of the procedure. In this setting over reliance on the BIS may lead to increased incidence of awareness.
  • This paper does not dismiss all the potential benefits of using BIS or Entropy but does highlight a major weakness that it maybe be unreliable when you depend on it the most
  • Despite the findings of this paper a recent Cochrane review demonstrated no increased incidence of awareness in patients using Level of Awareness monitors, even though this group received significantly less anaesthetic agents.
  • The findings of this study support an approach that avoiding paralysis where possible reduces the risk of awareness. In NAP 5 the risk of awareness of the unparalysed patient was 1:136,000 but this rose to 1:8,000 when muscle relaxant was used
For those interested, several other editorials and original scientific papers relating to risk of awareness and awareness monitoring were published in the same July edition of the BJA.


Idarucizumab for dabigatran reversal. NEJM June 2015.

Dabigatran is an oral thrombin inhibitor that is licensed for prevention of stroke in patients with non-valvular atrial fibrillation and prevention and treatment of venous thromboembolism. Although dabigatran is associated with less serious bleeding than warfarin, when life-threatening bleeding occurs. Current management of bleeding on dabigatran is limited to dialysis or supportive treatment with blood products which is only partially effective. Idarucizumab is a monoclonal antibody fragment which binds dabigatran with an affinity that is 350 times as high as with thrombin. Consequently, idarucizumab binds free and thrombin-bound dabigatran and neutralizes its activity.

This paper is an interim analysis of the first 90 patients enrolled in an ongoing, multicenter, prospective cohort study with the aim of recruiting 300 patients. Inclusion criteria are patients over 18 years of age taking dabigatran who present with life-threatening bleed or those requiring urgent surgery requiring dabigatran reversal. Idarucizumab was found to normalise diluted thrombin time and ecarin clotting time in 88 to 98% of patients, an effect which was evident within minutes of administration. Concentration of unbound dabigatran remained below 20ng/mL (no clinical effect) at 24 hours in 79% of patients. 1 patient had a thrombotic event within 72 hours after idarucizumab administration. These early results show promising signs that idarucizumab will be routinely used in the near future for dabigatran reversal.

Alcohol-based hand sanitizer: a potentially fatal toy. MJA July 2015

This is an interesting case report of a 3-year-old girl who presented to ED with suspected acute ethanol toxicity from ingestion of an alcohol-based hand sanitiser. She presented with a GCS of 10 and developed hypotension BP 70/22 requiring fluid boluses and peripheral adrenaline infusion. She was admitted to PICU without intubation and discharged 24 hours later. Serum ethanol concentration was 260mg/dL (legal blood ethanol level for drivers is <50mg/dL). This particular sanitiser has 70% ethanol and it is thought that she ingested a total of 55mL. The author highlight the hazards associated with hand sanitiser ingestion.

Peri-operative management of the obese surgical patient 2015. AAGBI, Society for Obesity & Bariatric Anaesthesia. Anaesthesia June 2015.

This consensus statement was developed because of the increased recognition that obese patients present a different set of challenges and require specific peri-operative care. This guideline serves as a good revision all of us and is also particularly useful for those sitting part 1 & part 2 exams.

In summary there are 16 points of recommendation:

  1. Every hospital should nominate an anaesthetic lead for obesity.
  2. Operating lists should include the patients’ weight and body mass index (BMI).
  3. Experienced anaesthetic and surgical staff should manage obese patients.
  4. Additional specialised equipment is necessary.
  5. Central obesity and metabolic syndrome should be identified as risk factors.
  6. Sleep-disordered breathing and its consequences should always be considered in the obese.
  7. Anaesthetising the patient in the operating theatre should be considered.
  8. Regional anaesthesia is recommended as desirable but is often technically difficult and may be impossible to achieve.
  9. A robust airway strategy must be planned and discussed, as desaturation occurs quickly in the obese patient and airway management can be difficult.
  10. Use of the ramped or sitting position is recommended as an aid to induction and recovery.
  11. Drug dosing should generally be based upon lean body weight and titrated to effect, rather than dosed to total body weight.
  12. Caution is required with the use of long-acting opioids and sedatives.
  13. Neuromuscular monitoring should always be used whenever neuromuscular blocking drugs are used.
  14. Depth of anaesthesia monitoring should be considered, especially when total intravenous anaesthesia is used in conjunction with neuromuscular blocking drugs.
  15. Appropriate prophylaxis against venous thromboembolism (VTE) and early mobilisation are recommended since the incidence of venous thromboembolism is increased in the obese.
  16. Postoperative intensive care support should be considered, but is determined more by co-morbidities and surgery than by obesity per se.

Excuse me, doctor: I can still hear you. BMJ June 2015.

This is an article from the BMJ written by a patient. The author relates her fear and loss of trust in her anaesthetist after over hearing the way he spoke inappropriately in theatre. Something for us all to keep in mind.


Epidural analgesia in patients with traumatic rib fractures: a systematic review of randomised controlled trials. ActaAnaesScand July 2015.

This article undertakes a systemic review of the evidence of benefit or harm of continuous epidural analgesia (CEA) vs other analgesic interventions from RCTs in patients with traumatic rib fractures as of July 2014. It uses the guidelines recommended by the Cochrane Collaboration . Overall it included six trials including 223 patients, and determined that in these studies there was currently no evidence of statistical difference in outcomes of mortality, duration of mechanical ventilation or pneumonia between CEA and other analgesic interventions. It pointed out that the included trials showed a potential for a high risk of bias. The analysis showed that the amount of information currently available to accurately determine whether there is a clinical benefit or harm with the use of continuous epidural analgesia vs other analgesic techniques (such as systemic opioids, paravertebral block etc) is inadequate and that a good quality large RCT is required in this patient population to provide accurate outcome information.


When and how to discuss “do no resuscitate” decisions with patients. BMJ May 2015.

This article is particularly relevant to us following Dr Mark Priestley’s recent grand round presentation on end of life issues. Rulings from the Court of Appeal from “The Tracey case” last year in the UK has resulted in two important changes to the do no resuscitate guidelines:

  1. Patient distress is no longer sufficient justification for not discussing do not resuscitate decisions with patient. Doctors must discuss a DNR order unless they consider it is likely to cause the patient “physical or psychological harm”
  2. Futility is not a valid argument for not discussing a DNR order with a patient. The fact that a treating clinician considers that CPR will not work means that the patient cannot require him or her to provide it. The patient should though be entitled to know that the clinical decision has been taken and should be given the opportunity to seek a second opinion if desired.
The emphasis in the article is that if a not for resuscitation order is made, we should discuss this with the patient involved.

Warfarin-induced skin necrosis following recommencement of warfarin after perioperative Prothrombinex-VF. MJA May 2015.

This case study discusses the case of a patient who developed warfarin-induced skin necrosis (WISN) – a rare complication induced by a transient paradoxical hypercoagulable state.  This patient had Prothrombinex-VF only (without vitamin K or FFP) for warfarin reversal for an urgent AAA repair, and developed widespread WISN following reintroduction of warfarin therapy post operatively. The author highlights that vitamin K should be administered with Prothrombinex-VF during warfarin reversal as it sustains the reversal effect, may increase the levels of anticoagulants protein C and S, and avoiding potential thrombotic complications.

Variability in practice and factors predictive of total crystalloid administration during abdominal surgery: retrospective two-centre analysis. BJA January 2015.

This study is an analysis of the volume and type of crystalloid prescribed in two major hospitals in the US and the factors that determined the volume administered. This month Professor Garry Morgan sent an email to all of Westmead’s medical staff suggesting that the current prescription of maintenance fluids was suboptimal and potentially contributing to post operative complications. His email included an extract from a BJA editorial published in April that accompanied this paper.

Scientific evidence for best practice intra and post-operative fluid management is still limited and evolving. The purpose of this study was to determine what constitutes current practice in centres that do not have protocolised fluid administration and what factors determines that practice.

Patients were ASA 1-3, undergoing elective abdominal surgery between 2009 and 2011. Exclusion criteria included emergency cases, cases with intraoperative complications, blood loss greater than 500mls, those requiring colloids, blood products or procedures of duration less than 1 hour. The lengthy exclusion criteria were designed to produce as homogenous a surgical population as possible.

The data collection resulted in approximately 6000 patients that were used to build a regression model. In order to compensate for variability in patient size and duration of operation, fluid administration was recorded in mls/kg/hr.

The average rate of fluid administration was 7ml/kg/hr for the whole study population. For an 80 kg patient this results in an average rate of infusion of approximately 550ml/hr.

Determining factors analysed in the regression model included patient factors (HR, UO, MAP, Age, weight) procedural factors (blood loss, epidural used, type of surgery) and the individual surgeon and anaesthetist involved in the case. The regression model then allows you to assess the impact of each factor of interest, once all others have been adjusted for.
Perhaps unsurprisingly the single biggest factor affecting rate of fluid administration was who was giving the anaesthetic. There was significant variation of practice of each individual anaesthetist and significant variation between different practitioners. Average (mean) fluid infusion rates for an individual anaesthetist ranged from a low of 2.9ml/kg/hr (the fluid restrictors) to a high of 14ml/kg/hr (the liberal infusers).

More surprisingly was the fact that patient factors including haemodynamic parameters, urine output, age, weight and estimated blood loss had no impact on the volume of fluid infused at all. ASA 3 patients did received slightly less than ASA 1 patients undergoing the same procedure. The most significant factor was if the surgeon insisted on a restrictive approach.

This paper does not attempt to measure the impact the various fluid administration strategies had on patient outcomes but seeks to describe the current chaos with which intraoperative fluid management is occurring, with the single biggest factor that determines how much fluid the patient receives being who turns up to give the anaesthetic and what kind of mood they are in that day.

The accompanying editorial is also well worth reading. Some of the key points are:
  • Whilst the ideal fluid strategy remains controversial, it is unlikely that those giving an average of 3mls/kg/hr and those giving 14mls/kg/hr are both correct.
  • The scientific evidence for restrictive fluid administration is increasing but the studies accessing this also have significantly different ideas about what constitute ‘normal’ care
  • Adherence to ‘enhanced recovery’ strategies for optimal oral hydration and carbohydrate loading prior to surgery are showing benefit in the UK. The aim being for your patient to arrive in OT in a euvolaemic state and then to maintain this during the procedure.
  • Hartmann’s, Plasmalyte and normal saline are intended for resuscitation or volume replacement and are not maintenance fluids. Each bag of Hartmann’s contains twice the daily requirement of NaCl (the same amount of salt that is found in 10 bags of chips) and this sodium load leads to fluid retention, odema and surgical complications
  • 5% dextrose or 0.18% saline + dextrose are appropriate post surgical maintenance fluids and 1ml/kg/hr  (up to a maximum of 2L of 5% dextrose in a 24 hr period) should be sufficient fluid until oral hydration is established
  • Patients should be transitioned to oral hydration and IV lines discontinued as soon as possible
  • If this is not possible the patient and blood work should be reassessed and a tailored fluid strategy should be produced

Co-author author of the editorial Professor Mythen is interviewed on the subject for the BJA podcast from April:


Dose-dependent association between intermediate-acting neuromuscular-blocking agents and postoperative respiratory complications. Anesthesiology June 2015.

This is an article that follows on from Dr Neil Warwick's recent lecture. It discusses a proportional increase in post-op respiratory complications based on the amount of neuromuscular blockade that is administered. End lesson: we don't monitor them and adequately reverse our patients, as a result, the more muscle relaxant we give the more respiratory complications result.