This website is intended for healthcare professionals only.

Hospital Healthcare Europe
Hospital Pharmacy Europe     Newsletter    Login            

Advancing the safety and efficacy of IV therapy

The biggest single advance in the safety of fluid therapy has been the recognition of its ‘Cinderella’ status in patient management

Neil Soni MD

Consultant, Anaesthesia and Intensive Care 

Honorary Senior Lecturer Imperial College

Chelsea and Westminster Hospital 

London, UK

The idea of using intravenous fluid is far from new. Thomas Latta used intravenous saline for cholera in 1832 and William O’Shaunessy published the method in the Lancet the same year. At the time the treatment had both enthusiasts and sceptics. The first documented use of saline for resuscitating haemorrhagic shock in humans was reported in the Lancet in 1882. Further controversy involved choice of fluid. The benefits of saline over glucose, albeit in resuscitating dogs, were already being discussed in Germany in the 1880s. This initiated the debate around ‘which fluid’ that may have altered in terms of the range of fluids involved but the controversy has never gone away. 

Complications were obviously a significant part of the early days of fluid therapy. The pioneer of blood transfusion Jean-Baptiste Denis around 1667 transfused a patient who subsequently died. When James Bovell used intravenous milk for cholera, five of seven patients died. Saline was clearly somewhat safer and there was no need for a randomised controlled trial. In these early days of a novel treatment the focus was on ‘which fluid’ yet the means of administration was also experimental with huge potential for complications as well as the associated hazards of infection, yet these problems were not discussed. The volumes used and how these might be estimated and even the theoretical basis of use was barely mentioned.

Advances in science and  safety

Advances in blood transfusion such as Landsteiner’s discovery of blood groups and the use of citrate made blood transfusion a realistic and a dramatically safer possibility. The use of crystalloids, mainly saline, became more practical and presumably safer, but already new fluids were being considered. Ringers solution was developed and tried based on the idea that it was more physiological than saline and the observation that frogs hearts performed better in vitro in this solution. 

Later colloids were introduced and meant to mimic the proposed, perceived and believed benefits of albumin solution. Intrinsic to these developments was a growing interest in the physiology of fluids and the circulation and the pathophysiology of fluid management in illness. Other advances were probably equally or more important. These included safer means of administering fluids. Open containers were replaced with sealed containers, sterility was introduced and sterile giving sets with filters were introduced to remove any solid matter and techniques for avoiding air entrainment. Materials also changed with the advent of plastic instead of rubber, glass or metal. Access changed with better sharp needles giving way to sharp safe needles, and plastic cannulae. Eventually reusable systems were replaced with single use. Each of these revolutionised the practicality of fluid administration and improved safety. Initially almost all these improvements in safety were associated with enhanced efficacy. 

As technology became more sophisticated, the consideration of safety aspects increasingly outweighed efficacy and there are now occasions where efficacy can  be reduced by the new safer devices.

In recent decades intravenous therapy has become ubiquitous in hospital practice and the repertoire of potential uses has increased phenomenally. The end result was that intravenous therapy is almost synonymous with hospital care and in the UK that involves more than 1.5 million patients a year. The developments in equipment, fluid type and the recognition of the potential complications in use of the equipment have made fluid management safer today than previously.  

Current issues

The paradox is that while all safety aspects have focused on fluid and equipment there has been little if any interest in fluid management itself.  That is to say the physiology and pharmacology of fluid administration. There has been little or no emphasis on the training involved in the prescription and administration of fluids, certainly in the UK but also elsewhere. Most fluid management and prescription is by junior doctors with minimal training in it and almost all fluid administration at the bedside is by nurses with less, although the latter are trained in the practical aspects of running through drip administration sets, assessing infusion rates manually and infection control. A recent publication once again highlighted the variable but often low level of knowledge and training of first year doctors who are the usual prescribers of fluid.1

In 1999 the National Confidential Enquiry into Perioperative Deaths (NCEPOD) noted that a significant number of patients died through too much or too little fluid and that as many as one in five patients on intravenous fluids suffered some complication. These ranged from electrolyte imbalance to infection and more. This came as no surprise but nothing changed and hence the same observation was reiterated in NCEPOD 2011. 

The problem is the way in which fluids are prescribed, administered and monitored. The gradual evolution of fluid management, often in relatively low intensity ward situations, has led to a perception of fluid management being simple and therefore devolved to the most junior members of the team. The diverse but ubiquitous nature of their use in wards across specialities means that everyone can and has to do it but that no one supervises and there is no one to take responsibility. The chain of command is weak with less involvement the higher up the chain one goes and no one has genuine interest. 

This phenomenon starts with medical school where it is a subject of very low interest and, in academic terms, non-existent. Most students will get far more teaching on the latest immunology or molecular science than on fluid management which is inversely proportional to practical application for doctors.  All medical students and nurses get some training in physiology and fluids but it is usually a token gesture. There is little or no follow-up when they reach the wards. In the 1970s fluid management was handed down often by the senior nurses who knew what was usually done by registrars who handed down what senior nurses had told them when themselves junior. 

Consultants often have limited knowledge or interest in fluids and that is often the remnants of the same training their juniors are getting.  Ward fluid management has traditionally been handed down and still is. Obviously there are bastions of expertise in every Institution. Anaesthetists, intensive care units, renal units, burns units and several special interest groups such as nutritionists have immense expertise.  In these areas fluids are central to management and are considered important. Teaching and training are effective and physiology based.  Complications are understood, identified early and treated.

They often do research in this field and their academic meetings often have time committed to fluids, more so in the last two decades. As with most experts the routine is considered mundane and they are usually fixated by relative minutia. In particular the old controversies such as which fluid, colloid crystalloid and the side effects of particular fluids fascinate. More recently ‘how much fluid’ is de rigeur, but in very specific and special circumstances and not in general ward management. As a general rule there is little or no interest outside of their defined areas except when they are asked to sort out problems. They almost never take an active interest in management, teaching or research in fluid use in ward areas. 

This lack of interest associated with considerable ignorance and almost total lack of leadership means that there is no feedback and hence problems are neither identified nor reported. There is no evidence that these complications occur because information is not collected centrally, yet few experienced clinicians would be unaware of the problem. With no formal recognition of problems and complications dispersed over the entirety of a hospital, there is no one with responsibility or jurisdiction to allow a cross-speciality audit. It is everyones’ problem, yet no-ones. That is all about to change. 

A guidline as an advance in safety

The single biggest advance in fluid safety since the description of blood types by Landsteiner has been the NICE clinical guideline 174 published in December 2013.2 It seeks to change fluids from being a Cinderella topic in hospital medicine to one that is recognised as clinically important and relevant. It will need a major change to the culture around fluid management, which is also the culture of ward-based hospital practice. 

There is recognition that those involved in fluid management and administration need a sound grounding in the basic physiology involved but also knowledge of the pharmacology of the drugs, in this case fluids, being used. Education is key and should provide the practitioner with an understanding and interest in what they are doing. It should not just be the prescriber but anyone who is involved in fluid management and the role of nurses is vital. This will require a firm medical and management commitment to allow this to happen.

The guideline itself is intended to be helpful and a template for culture change.  

The ‘how to’ parts of the guideline are not intended to be didactic but rather to provide information that can be used to decide what is appropriate. As in most aspects of medical practice, informed cognitive involvement is more effective and safer than rote activity. It is clear that it suggests practical ways of doing things but recognises the breadth and complexity of the field. As an evidence-based guideline it also highlights the paucity of good quality evidence in fluid management and thereby emphasises the need for a quality audit to identify the problems and research to clarify the issues. This latter finding is important because it emphasises just how neglected this topic has been. Both the complexity and size of the subject and the evidence base preclude didactism. 

The 5 R’s

A simple mechanism used in the guideline is to split fluid management into component areas. The areas are described as the 5 R’s are Resuscitation, Routine maintenance, Replacement, Redistribution and Reassessment.   Realistically the most important part of this is assessment that guides the need for fluid and reassessment that determines whether there are on-going fluid requirements or not. Many patients remain on fluids too long and many are given fluids when there is no need. The areas of the 5 R’s have algorithms to show management paths. 

How much?

A key issue is how much fluid is needed for maintenance. A common source of problems, especially in the elderly, is three litres a day for everyone. It is lost as to where three litres evolved from but it is almost invariably too much in all but very large (not obese) individuals.  The idea of one size fits all is absurd and so moving to an approach based on millilitres per kilogram makes this user friendly and inherently safe, and a working range is given. Again, the idea of regular reassessment means it can be adjusted if needed and, as this should include both physical examination and monitoring electrolytes, the latter can be used to modify the infusion. 

Limited fluid with the appropriate electrolyte balance is far less likely to cause problems, and if monitored it should become almost impossible.  

Obesity is a growing problem and poses issues in terms of what weight to use for fluid guidance. Fluid management in some situations is complex for the expert and so expertise will need to be sought on occasion. 

The specifics include identifying the need and implementing resuscitation based on basic physical signs, which ensures the system is functional in the ward and is a useful guide. The difficulties of replacement fluid for abnormal losses is inevitably complex and information is provided but the real message is, once again, ‘if in doubt ask advice’, preferably from someone with some expertise. 

Patient involvement

Patient involvement is discussed and seems obvious but even a cursory review of patients on intravenous fluids reveals that they are ill-informed of why they have a drip, often anxious and frequently aware that there is a problem such as pain or the fluid has run through. 


Apart from the 5 R’s there is a requirement that fluid management is audited, which requires a knowledge of what to look for and a list of complications describing what should be audited. This will provide a wealth of information about the frequency and type of complication and should be a useful guide.  The true epidemiology can be identified and addressed. 


There should be someone in hospitals with overall responsibility for this diverse yet ubiquitous area of practice. Finding individuals to take on roles that cross all the divides of profession and which involve a cultural change is a big challenge. 

The future

This guideline is the first, and most difficult step on a long road and it would be naïve to think change will happen instantly. The cost of this failure is, in every respect, too high. The problems of everyday fluid management have been massive and hidden beneath the surface. The guideline addresses that but on the surface there are also some safety issues being addressed. 

The fixation of anaesthetic and critical care professions with fluid type is one with which the regulatory authorities continue to struggle.  The starches have been used for some time but several studies have highlighted potential problems such as renal dysfunction and perhaps mortality. Nevertheless, there is undeniably a signal in the critically ill.3 It is an interesting problem from a regulatory viewpoint. The signal is not very strong and is in a very high-risk population, albeit ill-defined.

It is interesting to compare the safety profile of starch with the safety profiles of many ICU drugs.  Antibiotics, such as aminoglycosides, inotropes like noradrenaline, steroids, anticoagulants, nutritional support and even equipment such as ventilators have significant complications in the critically ill. It might be considered that no drug or intervention is safe in the critically ill but it is a risk-benefit analysis. How important is it compared to fluid management – not very. Controversy still surrounds albumin. Condemned by the Cochrane collaboration, vindicated by the SAFE study and now weakly advocated in sepsis it seems safe other than possibly in head injury.3

The safety of other fluids is debated. The race to demonstrate that chloride solutions are bad continues but the studies suggest there is less hyperchloraemia with lower chloride-containing solutions, but point out that more robust evidence of outcome alteration has yet to be forthcoming. It is probably realistic to say these discussions are the tip of the safety iceberg and again, of little relevance compared with the issues of basic fluid management. 

Other areas

The safe use of sharp devices is important but there should be care not to trade safety in one area with performance and efficacy reduction, which may threaten safety in others. Studies of these devices often indicate disadvantages such as slow flashback, blood leakage and increased resistance so presumably poor flow.4

A recommendation of the NICE guidelines involved the use of pumps for fluid administration. It will presumably be enhanced by a new generation of computerised smart pumps that have inbuilt means of checking safe prescription, safe flows and other features may help reduce prescription error.5 Technology is far more reliable than humans and should be applied to reduce human error and this is an excellent example of application. 

Infusion sets have often been plagued by the possibility of air entrainment, in particular when fluid in the bag runs out and so a new device is described where filters prevent this happening may be a potential step forward.6

PICC lines were hailed as being the solution to the problems of using central lines. With both improved ease of use and less complications they were clearly advantageous. In a recent study a complication rate of 11.77% included thrombosis, catheter related blood stream infections and cellulitis. These were always to be expected but is encouraging that some of these complications, mainly thrombosis, can be reduced by the judicious use of anticoagulants.7

An interesting diversion from hospital medicine is the growth in Outpatient Intravenous Antibiotic Therapy (OPAT). Managing patients out of hospital has a range of benefits, including cost and convenience, to the patients, hospitals and to health services involved. This will inevitability be an area of rapid growth and will almost certainly spread beyond antibiotics. From a therapeutic viewpoint it appears it is usually just as effective as being in hospital, but a lot cheaper and more pleasant for the patient.8–10 It is also an area where there will be safety issues. These are already being rigorously evaluated and generally it is recognised that OPAT needs to be introduced with a solid infrastructure of support. In direct contrast to the slow, random and uncontrolled evolution of hospital intravenous management, the issues are being anticipated identified and controlled.

A safe infrastructure, which involves teaching training audits and research are all being put into place. It needs to not only continue but also to be increased so that the complacency and issues that evolved in hospital practice can never happen. Prevention is much easier and more comfortable than cure. 

I recommend the NICE Clinical Guideline 174 as the most important and useful advance in fluid management in the last century.


  1. Powell AG, Paterson-Brown S. Safety through education. FY1 doctors still poor in prescribing intravenous fluids. BMJ 2011;342:d2741. PubMed PMID: 21586458.
  2. NICE Clinical Guideline 174.
  3. Myburgh J. Fluid resuscitation in acute medicine: what is the current situation? J Int Med 2014 Oct 28. PubMed PMID: 25352314.
  4. Ford J, Phillips P. An evaluation of sharp safety intravenous cannula devices. Nurs Stand 2011 Dec 14-2012;26(15-17):42–9. 
  5. Wood JL, Burnette JS. Enhancing patient safety with intelligent intravenous infusion devices: experience in a specialty cardiac hospital. Heart Lung 2012;41(2):173–6. 
  6. Salas Campos L, Palomino Barbero A. [New intravenous infusion: another step forward in patient safety]. Revista de enfermeria. 2011;34(3):8–12.
  7. Moran J et al. Screening for novel risk factors related to peripherally inserted central catheter-associated complications. J Hosp Med 2014;9(8):481–9. 
  8. Barr DA, Semple L, Seaton RA. Self-administration of outpatient parenteral antibiotic therapy and risk of catheter-related adverse events: a retrospective cohort study. Eur J Clin Microbiol Infect Dis 2012;31(10):2611–9. 
  9. Allison GM et al. Prediction model for 30-day hospital readmissions among patients discharged receiving outpatient parenteral antibiotic therapy. Clin Infect Dis 2014;58(6):812–9.
  10. Chapman AL. Outpatient parenteral antimicrobial therapy in a changing NHS: challenges and opportunities. Clin Med 2013;13(1):35–6.