The Department of Health and the National Assembly for Wales have asked the National Institute for Clinical Excellence (NICE or the Institute) to conduct an appraisal of the pre-hospital initiation of intravenous fluid in trauma and provide guidance to the NHS in England and Wales. The Appraisal Committee has had its first meeting to consider both the evidence submitted and the views put forward by the representatives nominated for this appraisal by professional organisations and patient/carer and service user organisations. The Committee has developed preliminary recommendations on the pre-hospital initiation of intravenous fluid replacement in trauma .

This document has been prepared for consultation with the formal consultees. It summarises the evidence and views that have been considered and sets out the preliminary recommendations developed by the Committee. The Institute is now inviting comments from the formal consultees in the appraisal process (the consultees for this appraisal are listed on the NICE website).

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.

The process the Institute will follow after the consultation period is summarised below. (For further details, see the Guide to the Technology Appraisal Process on the Institute's website).

• The Appraisal Committee will meet again to consider the original evidence and this Appraisal Consultation Document in the light of the views of the formal consultees.
• At that meeting, the Committee will also consider comments made on the document by people who are not formal consultees in the appraisal process.
• After considering feedback from the consultation process, the Committee will prepare the Final Appraisal Determination (FAD) and submit it to the Institute.
• Subject to any appeal by consultees, the FAD may be used as the basis for the Institute's guidance on the use of the appraised technology in the NHS in England and Wales.

The key dates for this appraisal are:

Closing date for comments: Thursday 2nd October 2003
Second Appraisal Committee meeting: Thursday 9th October 2003

Details of membership of the Appraisal Committee are given in Appendix A and a list of the sources of evidence used in the preparation of this document is given in Appendix B.

Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.

It is recommended that in the pre-hospital management of adults with trauma injuries, intravenous fluid (IV fluid) should not be administered if a radial pulse can be felt (or, for penetrating torso injuries, if a central pulse can be felt).

In the absence of a radial pulse (or a central pulse for penetrating torso injuries), it is recommended that IV fluid in boluses of no more than 250 ml should be administered, followed by reassessment until a radial (or central) pulse is palpable.

The administration of IV fluid should not delay transportation to hospital, but when given in accordance with 1.2 above, administration may take place en route to hospital.

It is recommended that crystalloid solutions should normally be administered in the pre-hospital setting.

There is inadequate evidence, and a lack of professional consensus, on which to base recommendations on the pre-hospital use of IV fluid in children with trauma injury. However, it is recommended that the general principles for IV fluid administration in children should be based on those recommended for adults. Thus, in children considered to be at risk of hypovolaemia, IV fluids should be administered in aliquots with frequent re-assessment of the child's physiological state and transfer to hospital should not be delayed.

It is recommended that only paramedics or other healthcare professionals who have been appropriately trained in advanced life-support techniques and pre-hospital care should administer IV fluid therapy to trauma patients in the pre-hospital setting and that training should incorporate the above recommendations.

The term 'trauma' is used to describe injuries caused by external force through accidents, violence or acts of self-harm. Injuries are broadly categorised by the mechanism of injury: either as penetrating, where the skin is punctured by a sharp object such as a knife or glass, causing external and potential internal bleeding; or as blunt injuries, where the skin is unbroken and the force of the injury ruptures the internal organs.

Blunt and penetrating injuries may cause severe bleeding and subsequent reduction in blood volume (hypovolaemia), which can lead to hypovolaemic shock (circulatory failure as a result of inadequate blood volume). If uncorrected, hypovolaemia will initially lead to inadequate perfusion and oxygenation of tissues and will subsequently cause permanent damage to vital organs and multiple organ failure, one of the major causes of death in trauma patients.

Data from the Office for National Statistics on the causes of death in England and Wales in 2000 state that 15,462 deaths were caused by injury. The Royal College of Surgeons suggests that approximately 14,500 fatalities arose from 545,000 trauma admissions in the UK in 1988. Department of Transport Statistics for motor vehicle crashes in England and Wales in 1998 reported that there were approximately 320,000 injuries involving road vehicles and around 3400 deaths. The majority of trauma in the UK results from blunt injuries (approximate ratio of 10:1, blunt to penetrating injuries).

Ambulance services across the UK differ in their composition and may comprise emergency medical technicians (EMTs) trained in basic life support (BLS), paramedics (emergency medical specialists) trained in advanced life support (ALS), or a combination of EMTs and paramedics. BLS involves establishing a clear airway, starting expired-air resuscitation in the absence of breathing, and starting external chest compression in the absence of a carotid pulse. ALS includes immediate therapy such as defibrillation, oxygen and cardioactive drugs, electrocardiogram monitoring, endotracheal intubation and setting up an intravenous infusion in a large peripheral or central vein. The British Association for Immediate Care (BASICS) also provides a service of voluntary doctors who are qualified in emergency medicine and equipped to attend accident scenes. Cannulation and administration of IV fluid can be undertaken by doctors or paramedics trained in ALS and may be initiated at the accident scene, in the ambulance en route to hospital, or in the accident and emergency department on hospital arrival.

Ambulance crews are usually the first healthcare professionals to attend an accident scene, where they assess the general physiological state of the patient to determine both what pre-hospital interventions are needed and the necessary speed of transfer to hospital, depending on injury severity. As part of the patient's evaluation a circulatory assessment is undertaken to ascertain the degree of blood loss. This involves identifying the site of bleeding (which may be external or internal), assessing whether there is a radial or central pulse, and determining the nailbed capillary refill time. Other indicators of haemorrhage in adults are tachycardia, peripheral vasoconstriction and reduced blood pressure (with blood loss of more than 750 ml). The severity of hypovolaemic shock is classified according to the extent of blood loss, from class I with less than 750 ml blood loss, to class IV with more than 2000 ml blood loss.

Fluid replacement therapy (intravenous infusion of fluid) attempts to reverse the effects of hypovolaemia by increasing circulatory blood volume and blood pressure, in order to maintain the perfusion of vital organs and to reduce the risk of death as a result of multiple organ failure.

IV fluids used in the treatment of trauma patients are regulated as medicines, and are broadly classified as crystalloids and colloids. Paramedics may legally administer crystalloid and colloid solutions, including succinylated modified fluid gelatine, compound sodium lactate intravenous infusion, sodium bicarbonate and sodium chloride infusions. Crystalloids are solutions of small ionic or non-ionic particles in water (that is, salt or small sugars such as glucose), which pass through cell membranes into the different body fluid compartments, approximately one third of the fluid remaining in the intravascular compartment. Colloid solutions contain large molecules (molecular weight > 10,000 daltons) of albumin, gelatins, polysaccharides or starch that are unable to cross cell membranes, and remain in the intravascular fluid compartment.

According to manufacturer list prices, the cost of crystalloids solutions is approximately £1-£1.80 per 500 ml unit compared with approximately £4-£16.50 per 500 ml unit for colloid solutions, excluding VAT. N.B. HyperHAES (a colloid solution), quoted as £28 per 250 ml unit, exceeds the approximate cost of other colloids. Costs may vary in different settings because of negotiated procurement discounts.

There are two approaches to the timing of IV fluid replacement in trauma. One approach is the initiation of IV fluid replacement in the pre-hospital setting; this may be done by paramedics or doctors trained in ALS either at the accident scene or in the ambulance en route to hospital. Administration of IV fluid before arrival at hospital may reduce the risk of tissue and organ damage in patients with severe hypovolaemia and may improve patient survival.

However, potential benefits from stabilising the patient before transportation should be balanced against risks associated with increased delays in reaching hospital and with the possibility that increased blood volume may exacerbate haemorrhage. Initiation of fluid replacement en route to hospital by paramedics or doctors trained in ALS confers any potential benefits of early fluid replacement whilst minimising time delays at the accident scene.

Alternatively, IV fluid replacement may be delayed until hospital arrival where patients receive definitive treatment for their injuries. Fluid may be administered before, or in conjunction with, the surgical management of haemorrhage. Delaying fluid replacement minimises delays at the accident scene, which is thought to be crucial to patient survival. Delaying fluid replacement is also believed to reduce the risk of re-bleeding caused by the mechanical disruption of blood clots and the dilution of clotting factors, which can occur, particularly when large volumes of IV fluid are administered.

The setting for the initiation of fluid replacement is the main focus of this appraisal; other issues, such as delayed hospital arrival and the efficacy of different fluid types, are subsidiary considerations.

In the absence of data on the audit and monitoring of JRCALC guidelines for IV fluid replacement in trauma, it is difficult to establish current adherence to these recommendations. However, some anecdotal evidence suggests that they are not always followed.

The Appraisal Committee considered evidence from a number of sources (see Appendix B).

The Assessment Report identified randomised controlled trials (RCTs) and systematic reviews of RCTs that compared pre-hospital IV fluid replacement with withheld (no pre-hospital) fluid. Observational studies cited in the evidence base of the consensus statement and JRCALC guidelines were also critically appraised. Seven studies were identified: two RCTs comparing immediate pre-hospital IV fluid replacement with delayed replacement; two RCTs comparing the use of different volumes of fluid for IV fluid replacement; two systematic reviews of RCTs of IV fluid replacement in humans and animals; and one observational study.

Studies that compared the effectiveness of ALS with BLS treatment of trauma were considered as proxies for pre-hospital and withheld IV fluid respectively. Six studies were identified: two systematic reviews, and four observational studies that formed the evidence base of the Consensus Statement and JRCALC guidelines.

One of the systematic reviews contained just one RCT, in which 2045 trauma patients in three areas of England (covering urban, suburban and rural areas) were randomised to treatment by paramedics or EMTs. Although the study was designed as an RCT, the results were analysed as a cohort study because poor protocol compliance meant only 16 patients were successfully randomised. When data from all areas were aggregated, the study showed that attendance by paramedics was associated with a non-significant increase in mortality (adjusted odds ratio, 1.74; 95% confidence interval, 0.89 to 3.41) but there was substantial regional variation (odds ratio 3.1 in area 1 and 0.78 in area 3).

Another systematic review included 13 observational studies and two reports of one RCT. Of these studies, in terms of mortality, 3/15 favoured ALS and 12/15 supported BLS (overall crude odds ratio 2.92, favouring BLS). Limiting the analysis to well-designed studies produced a crude odds ratio of 1.89 (favouring BLS to a lesser extent) but as confidence intervals were not stated it is not clear whether differences in mortality were statistically significant.

Four observational studies were cited in the Consensus Statement and JRCALC guidelines: two reported higher mortality in paramedic-attended patients, one favoured ALS and the other found that pre-hospital time did not affect survival. The results of these studies are included in the systematic reviews above. All of the studies were critically appraised and were considered to have serious methodological flaws, increasing the likelihood of bias, or to have controlled inadequately for confounding factors.

In summary, studies comparing ALS with BLS care of trauma patients provide insufficient evidence to demonstrate the benefit or harm of paramedic interventions. There was a trend towards poorer outcomes with ALS but it is not possible to determine whether this is due to the delay associated with ALS, due to the additional procedures undertaken, or because additional procedures may be undertaken in more severely injured patients with a poorer prognosis.

Intravenous infusion with different fluid types

As a subsidiary issue, systematic reviews of the effectiveness of IV infusion with different fluid types in a variety of settings were assessed.

Ten systematic reviews of RCTs were identified that compared different IV fluid types: four reviews were general comparisons of crystalloid and colloid solutions; the other reviews compared more specific IV fluid types (for example, isotonic crystalloid versus colloid; albumin-based colloid versus non-albumin solutions; comparisons of different classes of colloid; and hypertonic crystalloid [with or without dextran] versus isotonic crystalloid). The four systematic reviews that were general comparisons of IV fluid types showed a potential trend towards crystalloids being more effective than colloids, although the generality of these studies may have obscured the effect of individual crystalloid or colloid solutions. The Assessment Report concluded that as a result of clinical heterogeneity between studies (such as case-mix, additional interventions received, resuscitation protocols, amounts of IV fluid administered, and different types of colloids/crystalloids administered) and different types of patients being combined in meta-analyses, there was insufficient evidence of benefit of a particular IV fluid.

The additional cost of paramedic treatment (costs associated with trauma-related ALS training, salary and additional pre-hospital interventions) was presented per paramedic crew and per call out. The average unit cost of the ALS crew at £2.44 per minute was similar to the cost of a BLS crew at £2.43 per minute. There was a statistically significant increase of approximately £3 per ALS call out (average of £81.08 per ALS call out compared with £78.02 per BLS call out; p = 0.002) because of an extra 12 minutes spent at the scene by paramedics cannulating and initiating IV fluid therapy. The total cost (pre-hospital and hospital costs combined) of ALS and BLS was also estimated. There was a non-significant increase of £22 in the average total costs for patients attended by a paramedic-crewed ambulance (£2231 per patient, compared with £2209 per patient attended by EMTs alone). Between 20% and 30% of the cost of paramedic training and salary was attributed to trauma. Reductions in the level of trauma-related training had little effect on the overall cost of training.

Consideration of the evidence

The Committee considered that, although there was some evidence of benefit associated with delaying -the initiation of IV fluid until hospital arrival, no firm conclusions on clinical effectiveness could be drawn.

The Committee considered the extent to which evidence from the most methodologically sound RCT, which demonstrated a benefit in delaying IV fluid resuscitation in penetrating injuries, could be generalised to blunt injuries. The Committee heard, however, that the trial was based on the administration of larger quantities of IV fluid than would now be considered appropriate, and that it was, therefore, difficult to generalise the results to current clinical practice. In the absence of high-quality evidence on effectiveness, the Committee considered that guidance should take into account professional consensus, although the Consensus Statement and JRCALC guidelines were not formally evaluated by the Institute.

The Committee heard from experts that it would not be clinically appropriate to withdraw the use of IV fluid in a pre-hospital setting. The experts emphasised that there was a small proportion of hypovolaemic trauma patients at high risk of death who might benefit from pre-hospital initiation of IV fluid therapy; they explained that the aim of IV fluid in these circumstances is to prevent circulatory collapse without attempting to restore circulating volume or normal physiology.

The experts further advised the Committee that consideration should be given to whether trauma patients have controlled or uncontrolled haemorrhage. The Committee heard that it may be difficult to distinguish between trauma patients with controlled and uncontrolled haemorrhage in the pre-hospital setting, and that each has differential risks associated with the administration of IV fluid. Patients with severe uncontrolled bleeding with a volume loss that causes circulatory collapse are at the highest risk of cardiac arrest and death due to multi-system organ failure before hospital arrival if IV fluid is not administered. The experts also highlighted that IV fluid replacement in uncontrolled haemorrhage can exacerbate bleeding by diluting blood clotting factors and haemoglobin, and by dislodging early clots forming at the site of haemorrhage. In patients with controlled bleeding, the infusion of small volumes of IV fluid is unlikely to exacerbate bleeding. Taking these factors into account the Committee considered IV fluid therapy, administered in boluses of no more than 250 ml, to be clinically appropriate in all patients without a palpable radial pulse (or a central pulse in penetrating injuries of the torso), irrespective of whether or not bleeding is controlled. This should be followed by reassessment and administration of further boluses until a radial pulse (or a central pulse in penetrating injuries of the torso) becomes palpable. This would ensure that all hypovolaemic patients receive IV fluid, but not in sufficient volumes to exacerbate bleeding in patients where haemorrhage is uncontrolled. The Committee was advised that good patient-handling techniques in pre-hospital care were essential to minimise the risk of continued haemorrhage before the administration of IV fluid.

Experts advised that the guidance should take into account time constraints in reaching hospital, for example because of patient entrapment. The Committee concluded that there was inadequate evidence on which to base recommendations on the use of IV fluid in these circumstances.

In the absence of definitive evidence on the relative effectiveness of crystalloid and colloid solutions administered in the pre-hospital setting, the Committee was persuaded that the merits of different IV fluid types should be based on cost and risk of adverse events. On this basis, the Committee considered intravenous infusion with crystalloid solutions to be the preferred option because they are less expensive than colloid solutions and are not associated with hypersensitivity reactions seen in some patients when colloids are infused. In the absence of evidence on the relative effectiveness of different crystalloids, the Committee considered the use of normal saline, which has the lowest cost, to be the favoured option.

The Committee considered the issue of training for those administering pre-hospital IV fluid therapy, and concluded that only paramedics or other healthcare professionals with appropriate training in ALS techniques and pre-hospital care should administer IV fluid therapy to trauma patients in the pre-hospital setting.

It is strongly recommended that studies be undertaken to evaluate the appropriateness of pre-hospital IV fluid therapy, including consideration of specific patient groups, for example children, and patients with blunt versus penetrating injuries. Assessment of different protocols for pre-hospital care is essential in order to improve understanding of the risks and benefits of the use of IV fluids in this setting.

Preliminary views on the resource impact for the NHS

This section outlines the Appraisal Committee's preliminary assessment concerning the likely impact on NHS resources if the recommendations in Section 1 were to be implemented. When guidance is issued, this section is intended to assist NHS planners and managers in its implementation. Therefore the Institute particularly welcomes comments and information from those who would be involved in the implementation of the guidance so that this section can be made as helpful and robust as possible.

The cost of IV fluid replacement therapy in the pre-hospital phase is primarily determined by the unit cost of the IV fluid and the cost of the ambulance crew. A small cost increase for ALS was observed in the economic studies, predominantly because of increased on-scene times. There is also likely to be substantial regional variation in costs, according to unit costs of services across Ambulance Trusts.

Given the absence of reliable information on the current use and cost of pre-hospital IV fluids in people with trauma, it is difficult to quantify the likely cost of implementing the recommendations in section 1. However, limiting the use of pre-hospital IV fluid in the treatment of trauma patients would be unlikely to yield monetary savings within the ambulance service, but time saved at the accident scene may release resources within the ambulance service - contributing to improved response times - and may lead to small improvements in overall efficiency.

This section presents proposals for implementation and audit based on the preliminary recommendations for guidance in Section 1.

Ambulance trusts and clinicians who have been trained in ALS and pre-hospital care should review their current practice and policies to take account of the guidance set out in Section 1.

To measure compliance locally with the guidance, the following criteria could be used. Further details on suggestions for audit are presented in Appendix C.

IV fluid is not administered as part of pre-hospital management of an adult with a trauma injury if a radial pulse, or with a penetrating torso injury a central pulse, can be felt.

IV fluid consisting of a crystalloid solution in boluses of no more than 250 ml is administered as part of pre-hospital management of an adult with a trauma injury if no radial pulse is palpable, or no central pulse is detected in the case of a penetrating torso injury.

If IV fluid is administered, it is initiated en route to hospital (excluding individuals who are trapped).

When IV fluid is administered as part of pre-hospital management of an adult with a trauma injury, the individual is reassessed following each bolus of IV fluid and further boluses are withheld once a radial pulse (or a central pulse for an individual with a penetrating torso injury) is palpable.

IV fluid is administered to people experiencing trauma in the pre-hospital setting only by a paramedic or other healthcare professional who has been appropriately trained in ALS and pre-hospital care.

Training programmes for paramedics or other healthcare professionals are consistent with the guidance in Section 1.

Local clinical audits also could include measurement of compliance with other relevant clinical guidance such as JRCALC guidelines and the Consensus Statement.

There is no related guidance for this technology.

The review date for a technology appraisal refers to the month and year in which the Guidance Executive will consider any new evidence on the technology, in the form of an updated Assessment Report, and decide whether the technology should be referred to the Appraisal Committee for review.

It is proposed that the guidance on this technology is reviewed in January 2007.

Professor David Barnett

Chairman, Appraisal Committee

September 2003

NOTE The Appraisal Committee is a standing advisory committee of the Institute. Its members are appointed for a 3-year term. A list of the Committee members who took part in the discussions for this appraisal appears below. The Appraisal Committee meets twice a month except in December, when there are no meetings. The Committee membership is split into two branches, with the chair, vice-chair and a number of other members attending meetings of both branches. Each branch considers its own list of technologies and ongoing topics are not moved between the branches.

Committee members are asked to declare any interests in the technology to be appraised. If it is considered there is a conflict of interest, the member is excluded from participating further in that appraisal.

The minutes of each Appraisal Committee meeting, which include the names of the members who attended and their declarations of interests, are posted on the NICE website.

Dr Darren Ashcroft

Senior Clinical Lecturer, School of Pharmacy and Pharmaceutical sciences, University of Manchester

Professor John Brazier

Health Economist, University of Sheffield

Professor John Cairns

Professor of Health Economics, Health Economics Research Unit, University of Aberdeen

Dr Mark Chakravarty

Head of Government Affairs and NHS Policy, Procter and Gamble Pharmaceuticals (UK) Ltd, Egham, Surrey

Dr Peter I Clark

Consultant Medical Oncologist, Clatterbridge Centre for Oncology, Wirral, Merseyside

Professor Cam Donaldson

PPP Foundation Professor of Health Economics, School of Population and Health Sciences & Business School, Business School - Economics, University of Newcastle upon Tyne

Dr Paul Ewings

Statistician, Taunton & Somerset NHS Trust, Taunton

Ms Sally Gooch

Director of Nursing, Mid-Essex Hospital Services NHS Trust, Chelmsford

Miss Linda Hands

Clinical Reader in Surgery, University of Oxford

Professor Robert Kerwin

Professor of Psychiatry and Clinical Pharmacology, Institute of Psychiatry, London

Ms Ruth Lesirge

Dr George Levvy

Professor Andrew Stevens (Vice-Chair)

Department of Public Health, University of Aberdeen

Each appraisal of a technology is assigned to a Health Technology Analyst and a Technology Appraisal Project Manager within the Institute.

Eleanor Donegan and Zoe Charles

Technical Leads, NICE project team

Nina Pinwill (up to August 2003) and Dr Sarah Cumbers

Project Managers, NICE project team

A.

The assessment report for this appraisal was prepared by West Midlands Health Technology Assessment Collaboration, Department of Public Health and Epidemiology, The University of Birmingham:

I Dretzke J, Sandercock J, Bayliss S, et al. The clinical effectiveness and cost-effectiveness of pre-hospital intravenous fluids in trauma patients, July 2003

The following organisations accepted the invitation to participate in this appraisal. They were invited to make submissions and comment on the draft scope and assessment report. They are also invited to comment on the ACD and consultee organisations are provided with the opportunity to appeal against the FAD:

I Manufacturer/sponsors:

• Baxter Healthcare
  
• Fresenius Kabi
  
• Ivex Pharmaceuticals Ltd
  

II Professional/specialist and patient/carer group:

• Ambulance Service association
• British Association for Immediate Care (BASICS)
  
• British Association of Accident and Emergency
  
• British Association of Paramedics
  
• British Trauma Society
  
• Community Practitioners and Health Visitors Association
  
• Department of Health
  
• Faculty of Pre-hospital Care
  
• Joint Royal Colleges Ambulance Liaison Committee
  
• Royal College of Anaesthetists
  
• Royal College of Nursing
  
• Royal College of Physicians
  
• Royal College of Surgeons
  
• Royal Pharmaceutical Society
  
• The Facu

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