Anaesthesia 2014, 69, 399–419
Editorial
Editorial A defence of the NICE guidelines on intravenous fluids Thank you for the opportunity to respond to Dr Woodcock’s Editorial [1]. Most of his criticisms relating to colloid vs crystalloid and normal saline vs balanced solutions result from his taking discussion statements made in the full NICE guidance section Principles of Fluid Prescribing [2, pp 47–52] and presenting them as GDG conclusions/recommendations whilst omitting balancing text. This background section was never meant to be a definitive textbook of fluid and electrolyte prescribing but an outline of concepts that all fluid prescribers should understand. Some wording was derived from a B.Braun commissioned booklet [3] but B.Braun had no editorial input into the text and the GDG members who owned the intellectual property simply adapted the wording for our needs. Other GDG members then made significant alterations, particularly to material pertaining to the colloid and saline debates.
Colloids vs crystalloids There is no pro-colloid bias in our guidance. Indeed, there is no mention of colloids in any of the NICE algorithms or recommendations other than “Do not use tetrastarch for fluid resucitation” [2, Recommendation 17], and this follows the recommendation “If patients need resuscitation, use crystalloids. . ..” [2, Recommendation 16]. NICE only 416
allows ‘do not use’ statements where there is evidence of harm, as is the case for tetrastarches specifically. The evidence for gelatins is inconclusive and so we could not extrapolate the ‘do not’ recommendation to all colloids, instead suggesting further research. Although we discuss possible advantages of colloids in the background material, for example: “Synthetic colloids as well as albumin solutions have theoretical advantages over crystalloids in terms of their ability to expand intravascular volume rather than the interstitial space,” the use of the word ‘theoretical’ was very deliberate and the statement was balanced by its continuing: “but in recent years it has become clear that they are less effective in terms of intravascular volume expansion and retention than originally thought, especially in pathophysiological states when, in the presence of hypovolaemia and high capillary escape rates, all IV fluids have very different post-infusion distributions than in health. Colloids are also more expensive than crystalloids” [2, p95]. Similar balancing statements occur on every occasion throughout the NICE guidance that potential advantages of colloids are discussed. The assertion that we recommend colloids for urgent resuscitation is also incorrect and is derived
by quoting only part of our discussion of the fluid types used typically for replacement of ongoing losses. The full context reads: “Replacement for other losses e.g. GI or urinary, will usually depend on estimates of their composition but 0.9% sodium chloride, glucose 5% and glucose with saline solutions are all used (with or without additional potassium as appropriate) as are balanced crystalloid solutions. Colloids are not generally used in these patients unless their deficits are such that they need urgent resuscitation.” [2, p151]. This is not a GDG conclusion or recommendation, merely background discussion of current practice. The final criticism related to colloids applies to our recommendation “Consider human albumin solution 4–5% only for resuscitation in patients with severe sepsis” [2, Recommendation 18]. Here, we do agree that the wording is ambiguous but it seems unlikely this will be interpreted as our recommending using albumin alone for resuscitation in sepsis. We clearly meant only consider albumin use under these circumstances – an evidence based recommendation, even if unwelcome.
Normal or abnormal saline Serious iatrogenic salt and water overload is very common – a problem
© 2014 The Association of Anaesthetists of Great Britain and Ireland
Editorial
our guidance aims to reduce. Woodcock suggests that hyponatraemia will be a major threat if solutions such as Hartmann’s are used for resuscitation or regimens based on sodium chloride 0.18% in 4% glucose are used for maintenance. We disagree. Development of hyponatraemia in patients on intravenous fluids is usually a consequence of excess fluid rather than inadequate sodium provision and just as the treatment in most cases is fluid restriction rather than saline infusion, appropriate prevention is to limit total intravenous fluid provision rather than give normal saline when there is no saline deficit. Our recommendation that sodium (130–154 mmol.l 1) -based crystalloids should be used for resuscitation is in line with internationally recognised trauma guidelines that recommend Ringer’s (Na 130 mmol.l 1) or Hartmann’s (Na 131 mmol.l 1) for initial resuscitation [4], and a position statement from the Faculty of Intensive Care Medicine, the Royal College of Anaesthetists (RCoA), the Intensive Care Society and the College of Emergency Medicine states: “In most cases, fluid resuscitation should be undertaken with crystalloids that contain sodium in the range 130– 154 mmol/L. Use of physiologically ‘balanced’ solutions such as Hartmann’s solution, Ringer’s lactate or Plasmalyte 148 may be preferred over 0.9% sodium chloride” [5]. Woodcock’s assertion that hyponatraemic risks were ‘given little consideration’ also misrepresents our deliberations. For example, when paraphrasing our recommendation on the potential use of fifth-normal saline with glucose, he
Anaesthesia 2014, 69, 399–419
doesn’t mention that the recommendation applies only when prescribing for ‘routine maintenance’ – clearly defined as “fluid provision for patients that are essentially euvolaemic with no significant electrolyte deficits, ongoing abnormal losses or complex internal redistribution issues” [2, p. 134]. Furthermore, the full recommendation reads “When prescribing for routine maintenance alone, consider using 25–30 ml/kg/day sodium chloride 0.18% in 4% glucose with 27 mmol/l potassium. Prescribing more than 2.5 litres per day increases the risk of hyponatraemia. These are initial prescriptions and further prescriptions should be guided by monitoring.” [2, Recommendation 6]. Elsewhere in the guidance, we also say: “Routine maintenance provision should nearly always be a short-term measure since inappropriate therapy risks volume overload and electrolyte and acid-base disturbance particularly hyponatraemia” [2, p. 134] and “The use of 5% glucose will increase risks of significant hyponatraemia, particularly in children, the elderly, patients on diuretics and those with excess ADH due to osmotic and non osmotic stimuli (a problem seen quite frequently in hospitalized patients).” [2, p. 135]. It is therefore clear that we emphasise hyponatraemic risks throughout, as well as the need for close monitoring with daily plasma sodium evaluation. Furthermore, we did not define hyponatraemia as < 130 mmol.l 1 but recommended that fluid-related iatrogenic generation of this level of hyponatraemia should generate
© 2014 The Association of Anaesthetists of Great Britain and Ireland
a critical incident report [2, Recommendation 14]. Finally, the evidence supporting reduced oedema, complications, gut dysfunction and length of stay with lower sodium/chloride/volume approaches is stronger than would appear [6, 7]. The formal NICE evidence review of these issues was problematic since questions on optimal volume of fluid had to be separated from questions comparing fluid types, and much of the evidence for poorer outcomes with greater normal saline usage comes from studies where less total fluid was prescribed as well as less sodium and chloride. The evidence also had to be downgraded for ‘indirectness’ as most studies were not undertaken in the general ward settings at which our guidance is aimed.
Other criticisms Woodcock also criticises our recommendation to measure serum chloride in patients given fluids containing > 120 mmol.l 1 chloride. However, the evidence shows not only an association between hyperchloraemia and adverse events but also that hyperchloraemia occurs more frequently when using such fluids. The GDG therefore concluded that these patients should have daily chloride monitoring since hyperchloraemia contributes to reductions in renal blood flow and glomerular filtration [8, 9], though there was insufficient evidence to extend the recommendation to patients receiving any type of intravenous fluids. The suggestion that we should have recommended measurement of strong ion 417
Anaesthesia 2014, 69, 399–419
difference is interesting but there has been little discussion of this approach in the literature or the intensive care community, let alone evidence for using it in ward situations where there would be overwhelming problems of interpretation amongst staff. There is also criticism of our recommendation that resuscitation should commence with 500 ml fluid over < 15 minutes, with the opinion that 250 ml over an hour would often be more appropriate. However, our resuscitation recommendations clearly apply only to patients with signs of significant volume deficit, and 250 ml of any crystalloid over an hour would only alter intravascular volume by about 0.3–0.5%. There is no evidence to support the further suggestion that 250 ml over 10 minutes is ‘about right’ for hypotensive patients.
Conclusions The NICE intravenous fluid guidance is not intended for the intravenous fluids expert but to promote safer fluid prescribing by less experienced practitioners who often work unsupervised. It is evidence-based where possible, but pragmatic and based on expert (GDG) opinion where sound evidence was unavailable. Woodcock fails to recognise that current problems of poor fluid management are dominated by overprovision of salt and water and presents criticisms that are mainly based on misinterpretation. He also fails to acknowledge the most important elements of the NICE guidance: algorithms to support safe fluid prescribing in general ward areas 418
Editorial
including proper assessment of individual patients’ fluid needs and management plans to ensure proper clinical and laboratory reassessment. This is the first time that a national body has emphasised the importance of improving standards of intravenous fluid prescribing and our recommendation for ongoing clinical audit will also highlight this problematic area of clinical practice. Woodcock’s call to oppose implementation of the NICE recommendations should therefore be ignored and instead, more note taken of the opinions expressed by the RCoA in comments during consultation: “The document as a whole is of extremely high quality. Importantly the evidence base has been reviewed from a new start in the light of some evidence for colloids being subject to questionable research” and “The analysis of the RCTs has been done extremely well and we are in agreement with the evidence base, conclusions and recommendations made.” [10, p. 72 and p. 75].
Competing interests All the authors are members (and MAS the Chair) of the Guideline Development Group that produced the NICE Guidance on Intravenous Fluid Therapy in Adults in Hospital. No external funding declared. M. A. Stroud Chair of NICE GDG on Intravenous Fluid, Consultant Physician & Senior Lecturer in Medicine University Hospitals Southampton Southampton, UK Email: [email protected]
J. Nolan Consultant in Intensive care and Anaesthetics Royal United Hospital NHS Trust Bath, UK N. Soni Consultant in Intensive Care and Anaesthetics Chelsea and Westminster Hospital London, UK
References 1. Woodcock T. GIFTAHo; an improvement on GIFTASuP? New NICE guidelines on intravenous fluids. Anaesthesia 2014; 69: 410–415. 2. National Institute for Health and Care Excellence. CG174 Intravenous Fluid Therapy in Adults in Hospital: guide line. http://www.nice.org.uk/nicemedia/ live/14330/66013/66013.pdf (accessed 17/02/2014). 3. Lobo DN, Lewington AJP, Allison SP. Basic Concepts of Fluid and Electrolyte Therapy. Melsungen: Bibliomed – Medizinische Verlagsgesellschaft mbH, 2013. http://www.bbraun.com/documents/ Knowledge/Basic_Concepts_of_Fluid_ and_Electrolyte_Therapy.pdf (accessed 17/02/2014). 4. Resuscitation Council (UK). Advanced life support, 6th edition. London: Resuscitation Council (UK); 2011. 5. Position statement by the Faculty of Intensive Care Medicine, the Royal College of Anaesthetists, the Intensive Care Society and the College of Emergency Medicine. 2013http://www.rcoa. ac.uk/news-and-bulletin/rcoa-news-andstatements/risk-benefit-of-hes-solutionsquestioned-ema (accessed 17/02/ 2014). 6. Powell-Tuck J, Gosling P, Lobo DN, et al. British consensus guidelines on intravenous fluid therapy for adult surgical patients: GIFTASUP, 2011 http://www. bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf (accessed 17/02/2014). 7. Lobo DN. Intravenous 0.9% saline and general surgical patients: a problem, not a solution. Annals of Surgery 2012; 255: 830–2. 8. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, doubleblind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyteâ 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Annals of Surgery 2012; 256: 18–24.
© 2014 The Association of Anaesthetists of Great Britain and Ireland
Editorial 9. Yunos N, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloriderestrictive intravenous fluid administration strategy and kidney injury in critically ill adults. Journal of the
Anaesthesia 2014, 69, 399–419 American Medical Association 2012; 308: 1566–72. 10. Consultation comments on draft NICE CG174 Intravenous fluid therapy in adults in hospital: guideline, 2013. http://guidance.nice.org.uk/CG/Wave25/
© 2014 The Association of Anaesthetists of Great Britain and Ireland
5/Development/ConsultationComments Table/pdf/English (accessed 17/02/ 2014). doi:10.1111/anae.12689
419
Editorial
Editorial A defence of the NICE guidelines on intravenous fluids Thank you for the opportunity to respond to Dr Woodcock’s Editorial [1]. Most of his criticisms relating to colloid vs crystalloid and normal saline vs balanced solutions result from his taking discussion statements made in the full NICE guidance section Principles of Fluid Prescribing [2, pp 47–52] and presenting them as GDG conclusions/recommendations whilst omitting balancing text. This background section was never meant to be a definitive textbook of fluid and electrolyte prescribing but an outline of concepts that all fluid prescribers should understand. Some wording was derived from a B.Braun commissioned booklet [3] but B.Braun had no editorial input into the text and the GDG members who owned the intellectual property simply adapted the wording for our needs. Other GDG members then made significant alterations, particularly to material pertaining to the colloid and saline debates.
Colloids vs crystalloids There is no pro-colloid bias in our guidance. Indeed, there is no mention of colloids in any of the NICE algorithms or recommendations other than “Do not use tetrastarch for fluid resucitation” [2, Recommendation 17], and this follows the recommendation “If patients need resuscitation, use crystalloids. . ..” [2, Recommendation 16]. NICE only 416
allows ‘do not use’ statements where there is evidence of harm, as is the case for tetrastarches specifically. The evidence for gelatins is inconclusive and so we could not extrapolate the ‘do not’ recommendation to all colloids, instead suggesting further research. Although we discuss possible advantages of colloids in the background material, for example: “Synthetic colloids as well as albumin solutions have theoretical advantages over crystalloids in terms of their ability to expand intravascular volume rather than the interstitial space,” the use of the word ‘theoretical’ was very deliberate and the statement was balanced by its continuing: “but in recent years it has become clear that they are less effective in terms of intravascular volume expansion and retention than originally thought, especially in pathophysiological states when, in the presence of hypovolaemia and high capillary escape rates, all IV fluids have very different post-infusion distributions than in health. Colloids are also more expensive than crystalloids” [2, p95]. Similar balancing statements occur on every occasion throughout the NICE guidance that potential advantages of colloids are discussed. The assertion that we recommend colloids for urgent resuscitation is also incorrect and is derived
by quoting only part of our discussion of the fluid types used typically for replacement of ongoing losses. The full context reads: “Replacement for other losses e.g. GI or urinary, will usually depend on estimates of their composition but 0.9% sodium chloride, glucose 5% and glucose with saline solutions are all used (with or without additional potassium as appropriate) as are balanced crystalloid solutions. Colloids are not generally used in these patients unless their deficits are such that they need urgent resuscitation.” [2, p151]. This is not a GDG conclusion or recommendation, merely background discussion of current practice. The final criticism related to colloids applies to our recommendation “Consider human albumin solution 4–5% only for resuscitation in patients with severe sepsis” [2, Recommendation 18]. Here, we do agree that the wording is ambiguous but it seems unlikely this will be interpreted as our recommending using albumin alone for resuscitation in sepsis. We clearly meant only consider albumin use under these circumstances – an evidence based recommendation, even if unwelcome.
Normal or abnormal saline Serious iatrogenic salt and water overload is very common – a problem
© 2014 The Association of Anaesthetists of Great Britain and Ireland
Editorial
our guidance aims to reduce. Woodcock suggests that hyponatraemia will be a major threat if solutions such as Hartmann’s are used for resuscitation or regimens based on sodium chloride 0.18% in 4% glucose are used for maintenance. We disagree. Development of hyponatraemia in patients on intravenous fluids is usually a consequence of excess fluid rather than inadequate sodium provision and just as the treatment in most cases is fluid restriction rather than saline infusion, appropriate prevention is to limit total intravenous fluid provision rather than give normal saline when there is no saline deficit. Our recommendation that sodium (130–154 mmol.l 1) -based crystalloids should be used for resuscitation is in line with internationally recognised trauma guidelines that recommend Ringer’s (Na 130 mmol.l 1) or Hartmann’s (Na 131 mmol.l 1) for initial resuscitation [4], and a position statement from the Faculty of Intensive Care Medicine, the Royal College of Anaesthetists (RCoA), the Intensive Care Society and the College of Emergency Medicine states: “In most cases, fluid resuscitation should be undertaken with crystalloids that contain sodium in the range 130– 154 mmol/L. Use of physiologically ‘balanced’ solutions such as Hartmann’s solution, Ringer’s lactate or Plasmalyte 148 may be preferred over 0.9% sodium chloride” [5]. Woodcock’s assertion that hyponatraemic risks were ‘given little consideration’ also misrepresents our deliberations. For example, when paraphrasing our recommendation on the potential use of fifth-normal saline with glucose, he
Anaesthesia 2014, 69, 399–419
doesn’t mention that the recommendation applies only when prescribing for ‘routine maintenance’ – clearly defined as “fluid provision for patients that are essentially euvolaemic with no significant electrolyte deficits, ongoing abnormal losses or complex internal redistribution issues” [2, p. 134]. Furthermore, the full recommendation reads “When prescribing for routine maintenance alone, consider using 25–30 ml/kg/day sodium chloride 0.18% in 4% glucose with 27 mmol/l potassium. Prescribing more than 2.5 litres per day increases the risk of hyponatraemia. These are initial prescriptions and further prescriptions should be guided by monitoring.” [2, Recommendation 6]. Elsewhere in the guidance, we also say: “Routine maintenance provision should nearly always be a short-term measure since inappropriate therapy risks volume overload and electrolyte and acid-base disturbance particularly hyponatraemia” [2, p. 134] and “The use of 5% glucose will increase risks of significant hyponatraemia, particularly in children, the elderly, patients on diuretics and those with excess ADH due to osmotic and non osmotic stimuli (a problem seen quite frequently in hospitalized patients).” [2, p. 135]. It is therefore clear that we emphasise hyponatraemic risks throughout, as well as the need for close monitoring with daily plasma sodium evaluation. Furthermore, we did not define hyponatraemia as < 130 mmol.l 1 but recommended that fluid-related iatrogenic generation of this level of hyponatraemia should generate
© 2014 The Association of Anaesthetists of Great Britain and Ireland
a critical incident report [2, Recommendation 14]. Finally, the evidence supporting reduced oedema, complications, gut dysfunction and length of stay with lower sodium/chloride/volume approaches is stronger than would appear [6, 7]. The formal NICE evidence review of these issues was problematic since questions on optimal volume of fluid had to be separated from questions comparing fluid types, and much of the evidence for poorer outcomes with greater normal saline usage comes from studies where less total fluid was prescribed as well as less sodium and chloride. The evidence also had to be downgraded for ‘indirectness’ as most studies were not undertaken in the general ward settings at which our guidance is aimed.
Other criticisms Woodcock also criticises our recommendation to measure serum chloride in patients given fluids containing > 120 mmol.l 1 chloride. However, the evidence shows not only an association between hyperchloraemia and adverse events but also that hyperchloraemia occurs more frequently when using such fluids. The GDG therefore concluded that these patients should have daily chloride monitoring since hyperchloraemia contributes to reductions in renal blood flow and glomerular filtration [8, 9], though there was insufficient evidence to extend the recommendation to patients receiving any type of intravenous fluids. The suggestion that we should have recommended measurement of strong ion 417
Anaesthesia 2014, 69, 399–419
difference is interesting but there has been little discussion of this approach in the literature or the intensive care community, let alone evidence for using it in ward situations where there would be overwhelming problems of interpretation amongst staff. There is also criticism of our recommendation that resuscitation should commence with 500 ml fluid over < 15 minutes, with the opinion that 250 ml over an hour would often be more appropriate. However, our resuscitation recommendations clearly apply only to patients with signs of significant volume deficit, and 250 ml of any crystalloid over an hour would only alter intravascular volume by about 0.3–0.5%. There is no evidence to support the further suggestion that 250 ml over 10 minutes is ‘about right’ for hypotensive patients.
Conclusions The NICE intravenous fluid guidance is not intended for the intravenous fluids expert but to promote safer fluid prescribing by less experienced practitioners who often work unsupervised. It is evidence-based where possible, but pragmatic and based on expert (GDG) opinion where sound evidence was unavailable. Woodcock fails to recognise that current problems of poor fluid management are dominated by overprovision of salt and water and presents criticisms that are mainly based on misinterpretation. He also fails to acknowledge the most important elements of the NICE guidance: algorithms to support safe fluid prescribing in general ward areas 418
Editorial
including proper assessment of individual patients’ fluid needs and management plans to ensure proper clinical and laboratory reassessment. This is the first time that a national body has emphasised the importance of improving standards of intravenous fluid prescribing and our recommendation for ongoing clinical audit will also highlight this problematic area of clinical practice. Woodcock’s call to oppose implementation of the NICE recommendations should therefore be ignored and instead, more note taken of the opinions expressed by the RCoA in comments during consultation: “The document as a whole is of extremely high quality. Importantly the evidence base has been reviewed from a new start in the light of some evidence for colloids being subject to questionable research” and “The analysis of the RCTs has been done extremely well and we are in agreement with the evidence base, conclusions and recommendations made.” [10, p. 72 and p. 75].
Competing interests All the authors are members (and MAS the Chair) of the Guideline Development Group that produced the NICE Guidance on Intravenous Fluid Therapy in Adults in Hospital. No external funding declared. M. A. Stroud Chair of NICE GDG on Intravenous Fluid, Consultant Physician & Senior Lecturer in Medicine University Hospitals Southampton Southampton, UK Email: [email protected]
J. Nolan Consultant in Intensive care and Anaesthetics Royal United Hospital NHS Trust Bath, UK N. Soni Consultant in Intensive Care and Anaesthetics Chelsea and Westminster Hospital London, UK
References 1. Woodcock T. GIFTAHo; an improvement on GIFTASuP? New NICE guidelines on intravenous fluids. Anaesthesia 2014; 69: 410–415. 2. National Institute for Health and Care Excellence. CG174 Intravenous Fluid Therapy in Adults in Hospital: guide line. http://www.nice.org.uk/nicemedia/ live/14330/66013/66013.pdf (accessed 17/02/2014). 3. Lobo DN, Lewington AJP, Allison SP. Basic Concepts of Fluid and Electrolyte Therapy. Melsungen: Bibliomed – Medizinische Verlagsgesellschaft mbH, 2013. http://www.bbraun.com/documents/ Knowledge/Basic_Concepts_of_Fluid_ and_Electrolyte_Therapy.pdf (accessed 17/02/2014). 4. Resuscitation Council (UK). Advanced life support, 6th edition. London: Resuscitation Council (UK); 2011. 5. Position statement by the Faculty of Intensive Care Medicine, the Royal College of Anaesthetists, the Intensive Care Society and the College of Emergency Medicine. 2013http://www.rcoa. ac.uk/news-and-bulletin/rcoa-news-andstatements/risk-benefit-of-hes-solutionsquestioned-ema (accessed 17/02/ 2014). 6. Powell-Tuck J, Gosling P, Lobo DN, et al. British consensus guidelines on intravenous fluid therapy for adult surgical patients: GIFTASUP, 2011 http://www. bapen.org.uk/pdfs/bapen_pubs/giftasup.pdf (accessed 17/02/2014). 7. Lobo DN. Intravenous 0.9% saline and general surgical patients: a problem, not a solution. Annals of Surgery 2012; 255: 830–2. 8. Chowdhury AH, Cox EF, Francis ST, Lobo DN. A randomized, controlled, doubleblind crossover study on the effects of 2-L infusions of 0.9% saline and plasma-lyteâ 148 on renal blood flow velocity and renal cortical tissue perfusion in healthy volunteers. Annals of Surgery 2012; 256: 18–24.
© 2014 The Association of Anaesthetists of Great Britain and Ireland
Editorial 9. Yunos N, Bellomo R, Hegarty C, Story D, Ho L, Bailey M. Association between a chloride-liberal vs chloriderestrictive intravenous fluid administration strategy and kidney injury in critically ill adults. Journal of the
Anaesthesia 2014, 69, 399–419 American Medical Association 2012; 308: 1566–72. 10. Consultation comments on draft NICE CG174 Intravenous fluid therapy in adults in hospital: guideline, 2013. http://guidance.nice.org.uk/CG/Wave25/
© 2014 The Association of Anaesthetists of Great Britain and Ireland
5/Development/ConsultationComments Table/pdf/English (accessed 17/02/ 2014). doi:10.1111/anae.12689
419
