Preoperative saline versus gelatin for hip fracture patients; a randomized trial of 396 patients

M. J. Parker*,1, R. Griffiths2 and A. Boyle3

1 Department of Orthopaedicsand 2 Department of Anaesthesia, Peterborough District Hospital, Thorpe Road, Peterborough PE3 6DA, UK. 3 Department of Emergency Medicine,Addenbrooke’s Hospital, Cambridge, UK

*Corresponding author. E-mail: mjparker@doctors.org.uk

Accepted for publication: August 21, 2003


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Background. The aim of this study was to determine if the preoperative administration of 500 ml of a gelatin colloid solution intravenously before hip fracture surgery improves outcome, compared with a conventional i.v. fluid regime with a crystalloid solution.

Methods. Randomized, double blind, controlled trial of i.v. saline vs colloid for 396 patients having hip fracture surgery admitted to a district general hospital. Patients were followed up for 1 yr.

Results. There was no statistically significant difference between groups for mortality (30-day mortality 9/198 for saline group vs 19/198 for colloid group, 95% confidence intervals 0.21–1.02), length of hospital stay (22.5 days vs 17.3 days, 95% CI –10.78 to 0.38), or occurrence of postoperative complications.

Conclusions. The inclusion of 500 ml of colloid solution to the i.v. fluid regime before hip fracture surgery does not improve outcome.

Br J Anaesth 2004; 92: 67–70

Keywords: fluids, i.v., crystalloid solution; fluids, i.v., gelatin colloid; surgery, hip fracture


    Introduction
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 Abstract
 Introduction
 Methods
 Results
 Discussion
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Hip fractures generally occur in those aged approximately 80 yr in association with a fall. Blood loss from the fracture varies depending on the exact site and degree of displacement and comminution of the fracture, from a few millilitres to over 1 litre. Recent randomized studies on small numbers of patients using invasive cardiac monitoring have suggested that many of these patients are hypovolaemic at the time of surgery.13 Correction of this hypovolaemia was best achieved by colloid solution rather than crystalloid and resulted in improved haemodynamic parameters,1 2 and a tendency to a reduced hospital stay.2 3 This study aimed to see if we could demonstrate any benefits from using a colloid solution given preoperatively to a larger number of patients in the usual clinical setting without the availability of intensive intraoperative monitoring.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Between April 1999 and January 2002, 398 patients presenting with a hip fracture, which was to be treated operatively at Peterborough District Hospital, were randomized to receive before surgery either 500 ml of normal saline or 500 ml of gelatin (Gelofusine, Braun Medical Ltd) preoperatively. Each of these solutions were provided in identical containers enclosed in opaque plastic and then numbered sequentially by the hospital pharmacy department. Randomization was achieved when the next numbered study fluid was administered. Neither the patients nor the attending physicians were aware which solution was administered. No patient required un-blinding of the study fluid. All patients also received a standard i.v. fluid regime of saline started at the time of admission in the emergency department at a rate of 1 litre every 8–12 h. The exclusion criteria were those patients whose hip fracture was being treated conservatively, those with clinical signs of congestive cardiac failure, and those in which it was not possible to obtain informed consent from the patient or the assent of the next of kin. Care programmes for all patients were identical and once entered in the study all patients received one of the study fluids. Approval for the study was obtained from Peterborough and Fenland Local Research Ethics Committee.

Patients details recorded included age, sex, living in their own home (as opposed to institutional care), American Society of Anesthesiologists (ASA) grade, Mental test score,4 mobility score,5 type of anaesthesia used (general or regional), type of fracture (intracapsular or extracapsular), and type of surgery (arthroplasty or internal fixation). The mental test score is a series of 10 simple questions on recall and orientation. The mobility score provides an estimate of the patient pre-fracture mobility, from being able to walk and undertake shopping unaided (score 9), through to being bedridden (score 0). For the first 204 patients entered in the study the volume of preoperative, intraoperative, and postoperative (up to 5 days) i.v. fluids was recorded. Recording of these data was discontinued after the first 204 cases as it was time consuming to record and analysis of the data revealed no apparent difference between groups.

All patients were treated surgically with standard operative monitoring (intermittent arterial pressure, continuous ECG, pulse oximetry, capnography, and inhalation agent monitoring for general anaesthetic cases), but no invasive monitoring (arterial line, central venous pressure, or oesophageal Doppler ultrasonography). All surviving patients were followed until 1 yr from injury with no patient being lost to follow-up.

The primary outcome measure was mortality with secondary outcome measures of hospital stay, intraoperative decrease in arterial pressure, and medical complications. A decrease in arterial pressure was defined as a decrease of greater than 40 mm systolic from the preoperative value recorded on the theatre checklist chart. The criteria for the medical complications were: myocardial infarction–chest pain, raised enzymes and ECG changes; congestive cardiac failure–clinical signs requiring diuretic therapy; cerebrovascular accident–CT confirmation of clinical signs of hemiplegia; deep vein thrombosis—confirmed by ultrasound venography; and pulmonary embolism—confirmed by post-mortem, isotope scanning or CT.

The study was limited to 396 patients when the two trial solutions used for the study ceased to be made by the manufacturer in identical packaging. Statistical analysis between groups was with the Fisher exact test for binary variables and the un-paired t-test for continuous variables. A P-value of less than 0.05 was considered statistically significant. Mortality difference was studied with the log-rank test for equality of survivor functions throughout the whole trial and Kaplan–Meier survival curves were plotted.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Table 1 gives the characteristics of the patients. None of the differences between the two groups were statistically significant. Figure 1 shows the mortality for the two groups. The log-rank test for equality of survivor functions showed no statistically significant difference between groups (P-value=0.6). Table 2 gives the outcomes for the two groups. None of the differences between groups were statistically significant. Subgroup analysis for the different fracture types (intracapsular vs extracapsular) or general vs spinal anaesthesia showed no statistically significant difference in the outcome measure of mortality or length of hospital stay between groups. No adverse effects from the gelatin infusion occurred.


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Table 1 Characteristics of patients
 


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Fig 1 Kaplan–Meier survival graph.

 

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Table 2 Outcome measures for the two groups, number (percentages) or days and 95% confidence intervals for the difference between groups
 

    Discussion
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There have been three recent randomized studies on fluid resuscitation for hip fracture patients, all using small numbers of patients and invasive cardiac monitoring.13 Two of these,2 3 have been summarized in the Cochrane review on the topic.6 Sinclair and colleagues2 studied 40 patients having hip fracture surgery under general anaesthesia. Patients were randomized to either conventional intraoperative fluids or repeated colloid fluid challenges. Haemodynamics were monitored using oesophageal Doppler ultrasonography. Those in the fluid challenge group received approximately 750 ml more colloid during surgery and 300 ml less crystalloid. Those allocated to colloid challenges had a reduced length of hospital stay. Venn and colleagues3 in a study of 90 hip fractures, randomized patients to ‘normal care’, oesophageal Doppler or central venous pressure monitoring. They reported a reduced hospital stay for those allocated to fluid challenges with either CVP or oesophageal Doppler monitoring. Marhofer and colleagues1 measured haemodynamics with pulmonary artery and arterial catheters in 24 patients randomized to receive either 500 ml of 6% hetastarch or 1500 ml of Ringer’s lactate solution. At the time of surgery under spinal anaesthesia, haemodynamic impairment was reduced in those patients receiving the hetastarch. None of these studies followed patients beyond hospital discharge or assessed functional outcomes.

In contrast to these findings, a systematic review of the use of crystalloid vs colloid solutions for critically ill patients7 identified 37 randomized trials involving 1622 patients. There was a tendency to an increased mortality in those allocated to receive colloid solution. There have been no previous randomized studies using protocol-guided i.v. fluid therapy without invasive monitoring techniques in hip fracture patients. The present study also used patients having either general or regional anaesthesia, which was not possible for the studies of Sinclair2 and Venn.3 Spinal anaesthesia may be associated with a marginally lower early mortality for hip fracture patients but has no effect on long-term outcomes.8

Our study was not able to demonstrate that the inclusion of a fixed volume of 500 ml of colloid solution to the preoperative fluid regime had any demonstrable effect on either mortality or hospital stay, although there was a tendency to shorter total hospital stay (P=0.067) for those allocated to the colloid group (Table 2). This result may therefore have become significant if a larger number of patients had been included in the study. Nor were we able to demonstrate any benefits for subgroups of patients. In our study, we gave the colloid preoperatively but it may be that to be effective the colloid has to be given during surgery as in the studies of Sinclair2 and Venn.3 It is also possible that a future study would demonstrate that more invasive investigation of patients before or during surgery would be able to identify a sub-group of patients in whom colloid therapy or a more precise control of fluid balance or vasopressor use would be of benefit.


    Acknowledgements
 
We wish to thank Sharon Patrick for preparing the trial solutions and Braun Medical for providing all the trial solutions.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
1 Marhofer P, Faryniak B, Oismuller C, Koinig H, Kapral S, Mayer N. Cardiovascular effects of 6% hetastarch and lactated Ringer’s solution during spinal anesthesia. Reg Anesth Pain Med 1999; 24: 399–404

2 Sinclair S, James S, Singer M. Intraoperative intravascular volume optimisation and length of hospital stay after repair of proximal femoral fracture; randomised control trial. BMJ 1997; 315: 909–12[Abstract/Free Full Text]

3 Venn RM, Steele A, Richardson P, Grands RM, Newman P. Monitoring for optimisation of the hip risk surgical patient—arterial pressure, CVP or stroke volume? Int Care Med 2000; 26 (Suppl. 3): S333

4 Qureshi KN, Hodkinson HM. Evaluation of a ten-question mental test in the institutionalized elderly. Age Ageing 1974; 3: 152–7[Medline]

5 Parker MJ, Palmer CR. A new mty score for predicting mortality after hip fracture. J Bone Joint Surg 1993; 75B: 797–8

6 Price J, Sear J, Venn R. Perioperative fluid volume optimization following proximal femoral fracture (Cochrane Review). In: The Cochrane Library, Issue 1. Oxford: Update Software, 2003

7 Schierhout G, Roberts I. Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials. BMJ 1998; 316: 961–4[Abstract/Free Full Text]

8 Parker MJ, Griffiths R, Urwin S. Anaesthesia for hip fracture surgery in adults (Cochrane Review). In: The Cochrane Library, Issue 2. Oxford: Update Software, 2003