Written by Dr C. Williams

Caffeine accelerates recovery from general anesthesia via multiple pathways. Fong R, Khokhar S, Chowdhury A et al. Journal of Neurophysiology 2017;118:1591-1597 doi:10.1152/jn.00393.2017

Currently there is no method to accelerate emergence from general anaesthsia. Patient’s wake when they clear the anaesthetic from their systems. Drugs that had the ability to reverse the coma-like state induced by general anaesthetic agents would likely have considerable utility in clinical settings. In 1975 it was shown that direct intraventricular application of a membrane permeant cAMP analog could accelerate recovery from a variety of anaesthetic and sedative agents.

In 2014 the authors of this study demonstrated that drugs that increase intracellular cAMP dramatically accelerated emergence from anaesthesia. Three intravenous agents that increase cAMP levels were tested – forskolin, theophylline and caffeine – caffeine was shown to accelerate emergence time when anaesthesia was maintained with isoflurane 2%. This study aimed to determine whether caffeine had the same effect at higher anaesthetic concentrations. In this study, rats were anaesthetised for 60 minutes with end-tidal isoflurane levels of 3%. Ten minutes before anaesthesia was terminated the rats were injected with either saline (as a control) or a solution containing caffeine. Recovery time was taken as the time the rat was removed from the anaesthesia chamber, placed on its back on a table to the time it could stand with 4 paws on the table. This study appeared to show that caffeine accelerates emergence from anaesthesia even at high levels of isoflurane. The dose of caffeine was increased by 25mg/kg – starting at 25mg/kg and increasing to 75mg/kg. Caffeine at 75mg/kg produced a 55% reduction in emergence time

Caffeine inhibits phosphodiesterase which prevents the breakdown of cAMP. It also acts as an antagonist at all adenosine receptors. Blockade of the A adenosine receptor mediates caffeine’s arousal effects. Caffeine is already the most psychoactively used drug – in the USA more than 90% of adults use it daily. It is already used clinically either to treat neonatal apnoeas or for certain types of headache and is readily available.

However, this is a small study – no more than 9 rats were studied. There are also questions as to whether this study could be transferred to humans. Also the question as to whether a drug to accelerate emergence is necessary must be raised. It is tempting to speculate about other possible benefits of caffeine. Caffeine is known to have cognitive benefits – hence the reason it is one of the most widely used ‘drugs’. Anaesthetics can impair the cognitive abilities of patients, particularly the elderly, for significant periods of time. If caffeine was shown to accelerate cognitive recovery then it may play a significant role in postoperative recovery. To explore this theory would require extensive research.

Preoperative fluid retention increases blood loss during major open abdominal surgery. Hahn RG, Bahaman H, Nilsson L. Perioperative Medicine 2017;6:12 doi:10.1186/s13741-017-0068-1

Fluid management is an essential component in the management of major abdominal surgery. There is a marked variation in how the kidneys excrete or conserve fluid both in everyday life and preoperatively. Urine analysis can give a measure of the kidney’s state of fluid retention. It is known that a high concentration of urinary waste products is associated with a longer half-life of crystalloid fluid, a greater need for fluid optimisation, more complications after hip fracture surgery and a higher 30-day mortality in acute geriatric care. Little is known about how preoperative fluid retention affects intraoperative fluid balance. The aim of this study was to explore the relationship between preoperative dehydration and fluid requirements during major abdominal surgery with the hypothesis that fluid retention, indicating dehydration would mean more fluid is needed intra-operatively.

Patients undergoing elective open major abdominal surgery had their urine analysed for colour, specific weight, osmolality and creatinine concentration to calculate a fluid retention index. The fluid balance was obtained as the sum of infused fluid (crystalloid, colloid or blood products), minus the blood loss and excreted urine. Fluid retention was found in 37% of patients. It was associated with a significantly higher blood loss, a higher haemorrhage rate and a greater need for intravenous fluids. Despite the larger blood loss, the total fluid balance remained positive after surgery in dehydrated patients.

Preoperative dehydration is associated with higher fluid requirements intra-operatively but also a greater blood loss and a more positive fluid balance. These effects were most apparent in gynaecological and urological surgery. The results from this study would suggest that more fluid should be given to patients found to have concentrated urine preoperatively. More studies are needed to determine if this would improve patient outcome.

Paravertebral block does not reduce cancer recurrence, but is related to higher overall survival in lung cancer surgery: a retrospective cohort study. Lee EK, Ahn HJ, Zo J, Kim K, Jung DM, Park JH. Anaesthesia and Analgesia. 2017 doi:10.1213/ANE.0000000000002342 

Evidence is continuing to emerge about how postoperative analgesic methods have an impact on long-term prognosis after cancer surgery. Opioids trigger immune suppression by impairing innate immunity, altering antigen presentation and predominately favouring pro tumour cytokines. If a patient’s innate immunity is suppressed during the postoperative period there is the potential that remnant malignant cells or micro metastases may grow, establish and spread early after surgery.

Regional anaesthesia can reduce the need for opioids. Using this simple well known fact, it stands to reason that one would expect a lower cancer recurrence and higher survival if regional analgesic techniques were used instead of opioids. This was a large retrospective cohort study aiming to look at precisely this. They hypothesised that thoracic epidural or paravertebral catheters rather than intravenous opioids (via a PCA) as the postoperative analgesic method would be associated with better outcomes in patients undergoing lung cancer surgery.

The notes of 1729 patients undergoing open thoracotomy for primary non-small-cell lung cancer were reviewed. Patients either had a fentanyl PCA, a thoracic epidural with ropivacaine/hydromorphone solution or paravertebral catheter with ropivacaine infusion. Patients had what was then described as a ‘balanced’ anaesthetic  including opioids – either fentanyl boluses or remifentanil infusion. All patients had the same post-operative analgesic protocol for the next 2-3 weeks which was oral analgesics and/or fentanyl patch.

Recurrence rates were similar in all three groups and cancer recurrence was the cause of death in over 80% of the patients in each of the three groups. There was a statistically significant higher overall survival rate in the patients who received paravertebral catheters as the method of post-operative analgesia. Other variables were also related to overall survival including age, male sex, cancer stage, transfusion and duration and extent of surgery.

Unfortunately this study still does not help to answer the questions surrounding the role of anaesthetic techniques on cancer recurrence.

Regional anaesthesia and analgesia in cancer care: is it time to break the bad news? Sekandarzad MW, van Zundert A, Doornebal CW, Hollmann MW. Current opinion in anaesthesiology 2017;30(5):606-612 doi:10.1097/ACO.0000000000000492

The perioperative period is increasingly being recognised as a narrow but crucial window in cancer treatment. As the above paper hypothesises, regional anaesthesia has been proposed to reduce the incidence of cancer recurrence after surgery. There is a separate body of evidence suggesting that perioperative regional anaesthesia may be associated with a survival benefit in cancer patients.

The truth is that existing literature presents conflicting and inconclusive results about the impact of regional anaesthesia on cancer recurrence in patients undergoing surgery. Data is predominantly based on retrospective studies. with as many studies suggesting regional techniques have a positive outcome on cancer recurrence as those that suggest the opposite. The results from meta-analyses and systematic reviews are equally as conflicting. Conflicting results may be due to confounding factors including tumour-specific factors (such as type, grade and lymph invasion) which many studies do not take into account.

It seems unlikely that regional anaesthesia techniques either alone or in combination with modification of other perioperative factors can give clinically meaningful immune-protective effects when powerful chemotherapeutic agents appear to play a small role in cancer survival (contributing to 2% of the 5-year survival in adults). Additionally there is little convincing evidence that opioids promote cancer recurrence or facilitate the development of metastatic disease.

This review article critically refutes the concept that regional anaesthesia as a single modality in the complex oncological setting if cancer surgery can give positive cancer outcomes. The results of ongoing RCTs designed to investigate the link between regional anaesthesia and its ability to reduce cancer recurrence are eagerly awaited although it is unclear as to whether any clear results will be produced. Proving the efficacy of a single intervention (regional anaesthesia) in the multifactorial perioperative oncological setting will be challenging. What is clear is that a reducing postoperative pain and if possible preventing the progression to persistent post surgical pain, even at the expense of no difference in relation to reduced cancer recurrence, is still a goal to aim for.

European guidelines on perioperative venous thromboembolism prophylaxis: Surgery in the elderly. Kozek-Langenecker S, Fenger-Eriksen C, Thienpont E, Barauskas G, for the ESA VTE Guidelines Task Force. European Journal of Anaesthesiology 2017;34:1-7 doi: 10.1097/EJA.0000000000000705

The risk of venous thromboembolism (VTE) is higher in elderly patients particularly those aged over 70 years and elderly patients with co-morbidities. Large population-based epidemiological studies globally show that VTE predominantly occurs in the elderly and rarely occurs prior to late adolescence. But with an increased VTE risk comes an increased risk of bleeding. Therefore it is important to address this issue and ensure that there is appropriate risk stratification, correction of modifiable risks and sustained perioperative thromboprophylaxis.

Limited physiological reserves of older patients make them more vulnerable to postoperative stress and illness including VTE. Factors that have been associated in various studies with deep vein thrombosis and pulmonary emboli in there elderly include: congestive cardiac failure, pulmonary circulation disorders, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy, anaemia and coagulopathies.

Recommendations for VTE prophylaxis in the elderly are typically extrapolated from non-age specific VTE prophylaxis trials therefore timing and dosing of pharmacoprophylaxis are adopted from the non-aged population.

The general recommendations include:

  • Age over 70 is a risk factor for postoperative VTE
  • In elderly patients identify risk factors and correct if possible
  • Avoid bilateral knee replacements in elderly or frail patients
  • Timing and dosing of pharmacological VTE prophylaxis as in the non-aged population
  • In elderly patients with rena failure, low-dose un-fractionated heparin may be used or weight-adjusted dosing of LMWH
  • Careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation
  • Multi-faceted interventions for VTE prophylaxis in elderly and frail patients including pneumatic compression devices, LMWH (and/or direct oral anti-coagulants after knee or hip replacement)

Risk factors for postoperative ileus after colorectal cancer surgery. Rybakov EG, Shelygin YA, Khomyakov EA, Zarodniuk IV. Colorectal Disease 2017 doi:10.1111/codi.13888

Postoperative ileus is a temporary dysfunction of the gastrointestinal tract in response to surgical intervention. It is a common complication of abdominal surgery and most frequently developed after extensive colorectal operations. It causes significant financial and resource burden on healthcare institutions. The reduction in the incidence of ileus has therefore been placed as one of the top five priorities by the association of coloproctology of Great Britain and Ireland. Treatment is mainly symptomatic as there are no effective pharmacologic agents to treat it, therefore ileus prophylaxis based on the knowledge of potential risk factors is important.

300 patients having elective surgery for colorectal cancer were included. All patients had routine multimodal anaesthesia, a thoracic epidural (with a ropivacaine infusion) and the principles of enhanced recovery were followed: minimal preoperative starvation, no mechanical bowel preparation, no routine use of nasogastric tubes, maintenance of normothermia and minimisation of intraoperative infusions.

Ileus developed in 13% of the patients studied. After multivariate analysis four independent risk factors were identified: a BMI or 26 or over, previous abdominal surgery, the presence of extensive organ adhesions and the administration of opioids in the postoperative period. Importantly due to the fact that every patient in the study had an epidural with a plain ropivacaine infusion only a small proportion (10.7%) required opioids postoperatively. Yet a negative impact of opioids was demonstrated even at this small proportion.

It will never be possible to omit opioids in all patients but actively trying to use techniques that are opioid sparing may be a potential method in which anaesthetists can contribute to reducing the rates of postoperative ileus. This is however a retrospective and relatively small sized study therefore results should be interpreted with some caution.

The impact of fatigue on the non-technical skills performance of critical care air ambulance clinicians. Myers JA, Powell DMC, Adlington S, Sim D, Psirides A, Hathway K, Haney MF. Acts Anaesthesiologica Scandinavia 2017. doi:10.1111/aas.12994

Fatigue and how it affects performance is highly topical at the moment, particularly in anaesthetics following on from the publication of a national survey of the effects of fatigue on trainees in anaesthesia in the UK (Anaesthsia 2017;72:1069-1077) which was reviewed in July’s journal watch.*

This study looked at critical care doctors who are involved in air transfer of patients. The critical care air transport setting is dynamic and challenging and even a small performance decrement has the potential to affect clinical care and patient safety. Fatigue is presumed to negatively influence patient and clinician safety although the precise relationship is not entirely clear. It is also possible that sleep deprived clinicians may not recognise the extent to which their performance is impaired.

Nineteen physicians undertook two different simulated air ambulance missions, once while rested and once when fatigued. Performance was assessed by blinded observers based on expected behaviour in four non-technical skills domains: teamwork, situational awareness, task management and decision making. Participants also rated their own performances. They also completed a psychomotor vigilance task and a cognitive function test.

The physician’s non-technical skills were significantly better across all categories of skills and cognitive tests when rested. Clinicians completed relatively routine air transfer scenarios at levels of fatigue they routinely experience during usual clinical practice (e.g. towards the end of a night shift). Clinician’s also demonstrated limited awareness of their one degraded performance when fatigued. Self-ratings of performance showed no difference between fatigued and non-fatigued performance, in direct contrast to the rating provided by blinded observers.

This study highlights the importance of fatigue and how it can adversely affect performance. There is currently no good policy on recognising and managing the impact of fatigue in the NHS. Hopefully as awareness increases this will be addressed for all healthcare professionals, not only for the impact it has on patient safety but also the long term health impacts of chronic fatigue.

*A national survey of the effects of fatigue on trainees in anaesthesia in the UK. McClelland L, Holland J, Lomas J-P, Redfern N, Plunkett E. Anaesthesia 2017 doi:10.1111/anae.13965

Complications and unplanned admissions in non-operating room procedures. Leslie K, Kave B. Current opinion in Anaesthesiology 2017 doi:10.1097/ACO.0000000000000519 (13)

Increasing numbers of increasingly complex diagnostic and therapeutic procedures are being performed in areas remote from the operating theatre suite. This review aims to look at complications and unplanned admissions in patients requiring anaesthetic care for endoscopy, bronchoscopy and radiology procedures.

For endoscopy large analyses of databases show a low incidence of complications and unplanned admissions. In outpatients the incidence of cardiopulmonary complications was 0.9% – significant predictors included age over 60 years, higher ASA status and inpatient versus outpatient treatment.  Reviews of bronchoscopy seem to show that moderate sedation is tolerated well in these patients. Studies looking at procedures in radiology found that unplanned admissions were more likely to be due to pain, haemorrhage or infection as opposed to a sedation related problem.

Obstructive sleep apnoea has been associated with worse outcomes after procedures in the operating theatre. Studies have shown that OSA in patients having endoscopy or colonoscopy was not associated with any significant increase in cardiovascular or respiratory complications – the authors do make a note that caution should be applied in interpreting this due to poor methodological quality of the studies.

Overall, sedation seems to be associated with a low rate of complications – although some studies suggest more complications during deep propofol-based sedation rather than lighter benzodiazepine sedations. As anaesthetists we would like to think that if we provide the sedation as opposed to it being provided by a non-anaesthetist then it would be safer and have fewer complications. However, studies appear to suggest that sedation provided by anaesthetists is associated with more complications than if given by non-anaesthetists. The reasons for this are not explored but could be related to the fact that anaesthetists may provide sedation for higher risk patients and may provide a deeper level of sedation than non-anaesthetists. Clearly further randomised trials are required to define the optimum sedation drugs, sedation depth and the sedation provider.