Monty Mythen

Incidence of postoperative death and acute kidney injury associated with i.v. 6% hydroxyethyl starch use: systematic review and meta-analysis

BACKGROUND Trials suggest that the use of i.v. hydroxyethyl starch (HES) solutions is associ-ated with increased risk of death and acute kidney injury (AKI) in critically ill patients. It is uncertain whether similar adverse effects occur in surgical patients. METHODS Systematic review and meta-analysis of trials in which patients were randomly allocated to 6% HES solutions or alternative i.v. fluids in patients undergoing surgery. Ovid Medline, Embase, Cinhal, and Cochrane Database of Systematic Reviews were searched for trials comparing 6% HES with clinically relevant non-starch comparator. The primary end-point was hospital mortality. Secondary endpoints were requirement for renal replacement therapy (RRT) and author-defined AKI. Pre-defined subgroups were cardiac and non-cardiac surgery. RESULTS Four hundred and fifty-six papers were identified; of which 19 met the inclusion criteria. In total, 1567 patients were included in the analysis. Dichotomous outcomes were expressed as a difference of proportions [risk difference (RD)]. There was no difference in hospital mortality [RD 0.00, 95% confidence interval (CI) -0.02, 0.02], requirement for RRT (RD -0.01, 95% CI -0.04, 0.02), or AKI (RD 0.02, 95% CI -0.02 to 0.06) between compared arms overall or in predefined subgroups. CONCLUSIONS We did not identify any differences in the incidence of death or AKI in surgical patients receiving 6% HES. Included studies were small with low event rates and low risk of heterogeneity. Narrow CIs suggest that these findings are valid. Given the absence of demonstrable benefit, we are unable to recommend the use of 6% HES solution in surgical patients.

Perioperative increase in global blood flow to explicit defined goals and outcomes after surgery: a Cochrane Systematic Review

This systematic review and meta-analysis summarizes the clinical effects of increasing perioperative blood flow using fluids with or without inotropes/vasoactive drugs to explicit defined goals in adults. We included randomized controlled trials of adult patients (aged 16 years or older) undergoing surgery. We included 31 studies of 5292 participants. There was no difference in mortality at the longest follow-up: 282/2615 (10.8%) died in the control group and 238/2677 (8.9%) in the treatment group, RR of 0.89 (95% CI: 0.76-1.05; P=0.18). However, the results were sensitive to analytical methods and withdrawal of studies with methodological limitations. The intervention reduced the rate of three morbidities (renal failure, respiratory failure, and wound infections) but not the rates of arrhythmia, myocardial infarction, congestive cardiac failure, venous thrombosis, and other types of infections. The number of patients with complications was also reduced by the intervention. Hospital length of stay was reduced in the treatment group by 1.16 days. There was no difference in critical care length of stay. The primary analysis of this review showed no difference between groups but this result was sensitive to the method of analysis, withdrawal of studies with methodological limitations, and was dominated by a single large study. Patients receiving this intervention stayed in hospital 1 day less with fewer complications. It is unlikely that the intervention causes harm. The balance of current evidence does not support widespread implementation of this approach to reduce mortality but does suggest that complications and duration of hospital stay are reduced.

The role of nitrogen oxides in human adaptation to hypoxia.

Lowland residents adapt to the reduced oxygen availability at high altitude through a process known as acclimatisation, but the molecular changes underpinning these functional alterations are not well understood. Using an integrated biochemical/whole-body physiology approach we here show that plasma biomarkers of NO production (nitrite, nitrate) and activity (cGMP) are elevated on acclimatisation to high altitude while S-nitrosothiols are initially consumed, suggesting multiple nitrogen oxides contribute to improve hypoxia tolerance by enhancing NO availability. Unexpectedly, oxygen cost of exercise and mechanical efficiency remain unchanged with ascent while microvascular blood flow correlates inversely with nitrite. Our results suggest that NO is an integral part of the human physiological response to hypoxia. These findings may be of relevance not only to healthy subjects exposed to high altitude but also to patients in whom oxygen availability is limited through disease affecting the heart, lung or vasculature, and to the field of developmental biology.

Report from the meeting: Gastrointestinal Tonometry: State of the Art. 22nd-23rd May 1998, London, UK.

Abstract Gastrointestinal (GI) tonometry, the only clinically available method for the accurate diagnosis of compromised GI blood flow, has been shown to be a sensitive predictor of increased morbidity, mortality and prolonged hospitalization. The recent introduction of the Tonocap, as a means of performing automated air tonometry, has simplified the application of GI tonometry in the clinical setting. Despite this the utility of GI tonometry remains controversial. The GI Tonometry: State of the Art meeting brought together a group of clinicians with a proven track record of research, clinical interest and expertise in this field. The aim of the meeting was to come to a consensus regarding certain issues such as the past and future roles of GI tonometry and standards for its correct usage and interpretation. Finally suggestions as to further research and clinical evaluation were made within a broader discussion regarding the complexities of applying the principles of evidence-based medicine to the introduction of a new piece of medical technology.

Why is the surgical high-risk patient still at risk?

Over the last decades, we have seen a continuous improvement of perioperative anaesthetic and surgical care leading to a general reduction of morbidity and mortality, despite the surgical population getting older and with more co-morbidity. Nevertheless, and despite these improvements, there is a general agreement that the preoperative high-risk patient still carries a high risk of postoperative morbidity and mortality. How are we going to change this? Much attention has been paid to the ability to predict the individual patient at risk and several techniques have been developed from simple questionnaires to more invasive cardiopulmonary exercise tests, all showing some predictive value. – 4 Such preoperative risk stratification is valuable if it allows subsequent optimization of organ dysfunction and thereby reduction of surgical risk. To some extent, interventions such as cessation of alcohol and smoking use, exercise, and optimization of cardiopulmonary functional impairment have been shown to be effective. Concomitant with the improved knowledge on preoperative risk assessment, many single modality interventions have been tested in the perioperative setting, such as antibiotics, pain relief, regional anaesthetic techniques, fluid management, pharmacological sympathetic blockade, minimally invasive surgery, nutrition, reduced use of tubes, drains, etc. All have been shown to provide some effects on postoperative outcome (Fig. 1). Although much of this evidence has come from several randomized controlled clinical trials (RCTs) and subsequent meta-analyses, they usually examine single interventions in single or few centres and thus only determine efficacy (i.e. may work). Few trials take a more pragmatic account of effectiveness (i.e. are effective in routine clinical practice), rather than the single one in question for an efficacy study. Many studies have been flawed by not standardizing all elements of perioperative care to current best evidence-based practice (or by not providing specific information of such care principles). Such studies include effects of pain relief on outcome, 7 use of perioperative b-blockers, perioperative fluid management, 10 minimal invasive surgery, etc. Furthermore, allocation of patients from different surgical interventions may not be appropriate since the pathophysiology of morbidity is likely to be different between procedures. Hence the growing interest and increasing support for the use of registries, prospective cohort studies, or both as the final step along the innovation pathway. For example, over the past 10–12 yr, there has been a wider acceptance that postoperative morbidity and recovery problems should be considered as a multi-factorial problem that may not be solved by uni-modal interventions, but rather by a multi-modal intervention by combining several evidence-based principles of care. Subsequent research using this multi-modal, best-evidence based approach (e.g. the ‘fast-track methodology’ or ‘enhanced recovery programmes’) has shown in a growing number of well-designed prospective cohort studies or RCTs to enhance postoperative recovery and reduce length of stay, morbidity, and convalescence. – 16 Such is the level of acceptance of this approach that a number of European Countries now have Government-funded National Programmes for Enhanced Recovery (e.g. Holland, Denmark, Spain, and the UK). What then can we expect, and what should we further explore in future efforts to understand and change the Volume 106, Number 3, March 2011

Perioperative fluid management: Consensus statement from the enhanced recovery partnership

Enhanced Recovery (ER) after Surgery (or Fast Track) is a bundle of ‘best evidence based practices’ delivered by a multi-professional health care team, with the intention of helping patients recover faster after surgery [1]. Professor Henrik Kehlet, a surgeon from Denmark, pioneered the concept more than a decade ago but practitioners in the UK remained sceptical of his amazing results and adoption in the National Health Service (NHS) had been slow [1,2]. The Enhanced Recovery Partnership Programme (ERPP) was set up by the Department of Health in England in May 2009, to encourage the widespread adoption of ER with the aim of improving recovery from major surgery [1,3]. The Programme initially concentrated on elective major surgery in four specialities (Colorectal, Musculoskeletal, Gynaecology and Urology). Audit of ER practice by the early adopters demonstrated greater than 80% compliance with the majority of elements recommended by the ERPP. However, perioperative fluid management including the administration of pre-operative carbohydrate drinks and individualised goal directed fluid management guided by advanced haemodynamic monitoring (e.g. Oesophageal Doppler) had lower levels of compliance [3]. A pilot study using Commissioning for Quality and Innovation (CQUIN) to encourage practice change showed a dramatic improvement in outcomes in North Central London with very high levels of compliance with the ERPP recommended principles of perioperative fluid management, in particular goal directed fluid management [4]. The National Programme has evolved into the Enhanced Recovery Partnership (ERP), and the most recent guide published by the ERP includes evidence of widespread adoption of ER in the NHS in England and achievement of stated goals i.e. reduced length of hospital stay after surgery resulting in more operations being performed despite fewer bed days, no increase in readmissions and high levels of patient satisfaction [5]. Perioperative fluid management is at the heart of Enhanced Recovery and the use of intra-operative fluid management technology, such as Oesophageal Doppler, is supported by the ERP in line with the National Institute of Clinical Excellence (NICE) Guidance (MTG3), the NHS Operating Framework 2012–13 and the Department of Health Innovation Health and Wealth Review 2011 [5-7]. Despite concordance in the guidelines, the veracity of the evidence has been challenged [8,9]. The ERP thought it was timely to produce a consensus statement from the National Clinical Leads and Specialist Advisors within the specific context of Enhanced Recovery and, for the purpose of widespread dissemination, the general principles and key recommendations outlined in the latest guide are reiterated in this article [5]. Of note, no particular evidence based methodology was used aside from seeking unanimous agreement from the authors. A practical and pragmatic set of guidelines and recommendations was the aim. The conclusions do align with the GIFTASUP guidelines and NICE guidance where established EBM methodologies were utilised [6,8,10]. In making this consensus statement we agree that larger, more definitive studies of perioperative fluid management and, in particular, the relative contribution of haemodynamic monitoring compared with fluid restriction would be welcomed [11,12]. However, to be useful, such studies must be conducted in the context of a fully implemented Enhanced Recovery Program.

Maintaining blood flow in the extracorporeal circuit: haemostasis and anticoagulation

ObjectivesTo review the methods and developments in maintaining extracorporeal circuits in critically ill patients.DesignThe review includes details of the pathophysiological processes of haemostasis and coagulation in critically ill patients, methods of maintaining blood flow in the extracorporeal circuit and methods of monitoring anticoagulation agents used.SettingInformation is relevant to the management of critically ill patients requiring extracorporeal renal and respiratory support and cardiopulmonary bypass.ConclusionsHeparin is the mainstay of anticoagulation for the extracorporeal circuit although the complex abnormalities of the coagulation system in critically ill patients are associated with a considerable risk of bleeding. Alternative therapeutic agents and physical strategies (prostacyclin, low molecular weight heparin, sodium citrate, regional anticoagulation, heparin bonding and attention to circuit design) may reduce the risk of bleeding but expense and difficulty in monitoring are disadvantages.

Enhanced recovery from surgery in the UK: an audit of the enhanced recovery partnership programme 2009–2012

BACKGROUND The UK Department of Health Enhanced Recovery Partnership Programme collected data on 24 513 surgical patients in the UK from 2009-2012. Enhanced Recovery is an approach to major elective surgery aimed at minimizing perioperative stress for the patient. Previous studies have shown Enhanced Recovery to be associated with reduced hospital length of stay and perioperative morbidity. METHODS In this national clinical audit, National Health Service hospitals in the UK were invited to submit patient-level data. The data regarding length of stay and compliance with each element of Enhanced Recovery protocols for colorectal, orthopaedic, urological and gynaecological surgery patients were analysed. The relationship between Enhanced Recovery protocol compliance and length of stay was measured. RESULTS From 16 267 patients from 61 hospital trusts, three out of four surgical specialties showed Enhanced Recovery, compliance being weakly associated with shorter length of stay (correlation coefficients -0.18, -0.14, -0.25 in colorectal, orthopaedics and gynaecology respectively). At a cut-off of 80% compliance, good compliance was associated with two, one and three day reductions in median length of stay respectively in colorectal, orthopaedic and urological surgeries, with no saving in gynaecology. CONCLUSIONS This study is the largest assessment of the relationship between Enhanced Recovery protocol compliance and outcome in four surgical specialties. The data suggest that higher compliance with an Enhanced Recovery protocol has a weak association with shorter length of stay. This suggests that changes in process, resulting from highly protocolised pathways, may be as important in reducing perioperative length of stay as any individual element of Enhanced Recovery protocols in isolation.

Coagulation effects of in vitro serial haemodilution with a balanced electrolyte hetastarch solution compared with a saline-based hetastarch solution and lactated Ringer's solution

The hydroxyethyl starches are a group of compounds that has been associated with impairment of coagulation when large volumes are administered. The thrombelastograph® is commonly used to assess point‐of‐care whole blood coagulation. Little is known about the dose–response relationships of haemodilution, and it is reasonable to assume that a linear association exists. This may not be the case with altered electrolyte compositions of the fluids used for haemodilution. We have therefore conducted an in vitro study of haemodilution of human whole blood using lactated Ringers solution and two high molecular weight hetastarches, one in a balanced salt solution, the other in a 0.9% saline solution. The thrombelastograph®, commonly used for the assessment of the coagulation effects of synthetic colloids, was used as the coagulation assessment device. Serial haemodilution with hetastarch in a balanced salt solution demonstrated a biphasic response (of r‐times and k‐times, as well as alpha angles), with haemodilution in the 20–40% range causing enhanced coagulation, and higher degrees of dilution causing a decrease in overall coagulation performance. A similar picture was observed with lactated Ringers solution, but only significantly so in alpha angles. Hetastarch in saline did not display this initial increased coagulability at mild to moderate dilutions. This biphasic response of lactated Ringers solution and hetastarch in a balanced salt solution reflects the complex interaction of fluids and the coagulation system, and that these effects cannot be attributed to simple haemodilution. On the other hand, there was a linear decrease in maximum amplitude with haemodilution. Maximum amplitude was particularly affected by both starches, which is an expected finding in view of the known interaction between the hydroxyethyl starches and von Willebrands factor.

Consensus views on implementation and measurement of enhanced recovery after surgery in England: Delphi study.

Objective The Department of Healths Enhanced Recovery Partnership Programme (ERPP) started a spread and adoption scheme of Enhanced Recovery After Surgery (ERAS) throughout England. In preparation for widespread adoption the ERPP wished to obtain expert consensus on appropriate outcome measures for ERAS, emerging techniques being widely adopted and proposed methods for the continued development and sustainability of ERAS in the National Health Service. The aim of this study was to interrogate expert opinion and define areas of consensus on these issues. Design A Delphi technique using three rounds of reiterative questionnaires was used to obtain consensus. Participants Experts were chosen from teams with experience of delivering a successful ERAS programme across different surgical specialties and across various disciplines. Setting The first two rounds of the questionnaire were completed online and a final, third round was undertaken in a meeting using interactive voting. Results 86 experts took part in this study. Consensus statements agreed that patient experience data should be recorded, analysed and reviewed at regular ERAS meetings. Recent developments in regional analgesia, the increased use of intraoperative monitoring for fluid management and cardio-pulmonary exercise testing were the main emerging techniques identified. National standards for those outcome measures would be welcomed. To sustain success in ERAS, the experts highlighted clinical champions and the presence of a dedicated ERAS facilitator as essential elements. For future networking, a unanimous agreement was achieved on the formation a national network to facilitate spread and adoption of ERAS and to promote research and education across surgery. Conclusions Consensus was achieved on regular measurement and review of patient experience in ERAS. Agreement was reached on the role of regional analgesia and the use of oesophageal Doppler for intraoperative goal-directed fluid therapy. In order to facilitate the further spread and adoption of best practices and to promote research and education, an ERAS-UK network was recommended.