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Hypertonic versus near isotonic crystalloid for fluid resuscitation in critically ill patients

  1. Frances Bunn1,*,
  2. Ian G Roberts2,
  3. Robert Tasker3,
  4. Daksha Trivedi1

Editorial Group: Cochrane Injuries Group

Published Online: 19 JUL 2004

Assessed as up-to-date: 14 OCT 2007

DOI: 10.1002/14651858.CD002045.pub2


How to Cite

Bunn F, Roberts IG, Tasker R, Trivedi D. Hypertonic versus near isotonic crystalloid for fluid resuscitation in critically ill patients. Cochrane Database of Systematic Reviews 2004, Issue 3. Art. No.: CD002045. DOI: 10.1002/14651858.CD002045.pub2.

Author Information

  1. 1

    University of Hertfordshire, Centre for Research in Primary and Community Care, Hatfield, Hertfordshire, UK

  2. 2

    London School of Hygiene & Tropical Medicine, Cochrane Injuries Group, London, UK

  3. 3

    Department of Paediatrics, University of Cambridge School of Clinical Medicine, Cambridge, UK

*Frances Bunn, Centre for Research in Primary and Community Care, University of Hertfordshire, College Lane, Hatfield, Hertfordshire, AL10 9PN, UK. f.bunn@herts.ac.uk.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 19 JUL 2004

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Characteristics of included studies [ordered by study ID]
Bortolani 1996

MethodsRandomised controlled trial. Method of allocation concealment is not described.
No mention of blinding.


Participants40 patients, with burns over 30% of the body surface area admitted within 4 hours of trauma.
Country: Italy


Interventions
  1. Hypertonic lactated saline (n=20)
  2. Ringer's lactated saline (n=20)


OutcomesHaemodynamic variables.
Death.
Complications.


NotesLength of follow-up not clear.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Caldwell 1979

MethodsTreatments were alternated.
No mention of blinding.


Participants20 children with thermal burns covering 30% or more of the body surface area.
Country: USA


Interventions
  1. Hypertonic lactated Ringer's (n=17).
  2. Lactated Ringer's (n=20).


i.v. treatment discontinued after 48 hrs.


OutcomesDeath.
Haemodynamic variables.


NotesLength of follow-up not clear.
No loss to follow-up reported.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?NoC - Inadequate

Cooper 2004

MethodsDouble blind randomised controlled trial.
Identical bags of sequentially numbered, computer randomised fluid were packed in groups of 4 in each ambulance.


Participants229 patients with traumatic brain injury.
Country: Australia.


Interventions
  1. 250 ml of Hypertonic saline (7.5%).
  2. 250 ml of ringers lactate.


OutcomesDeath.
Disability (glasgow outcome scale).
Cognitive score.
Functional independence score.


NotesFollow up 6 months.
One patient in control group declined to participate and two in intervention were lost to follow-up.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Croft 1992

MethodsRandomised controlled trial. Patients were divided consecutively, with a random allocation chart. Method of allocation concealment was not described.
No mention of blinding.


Participants28 patients undergoing major intra-abdominal surgery. Patients with an abnormality of a cardiac valve, liver failure, pacemaker, shock, septicemia or presence of myocardial ischemia less than 24 hours before the study were excluded.
Country: Canada.


Interventions
  1. Hypertonic saline (n=13).
  2. Isotonic Ringer's lactate (n=15).


Preoperatively RL or HS were infused at a rate sufficient to maintain a PAWP and a CVP within 3 mm Hg of the initial value.


OutcomesHaemodynamic variables.
Death.


NotesFollow up 72 hours.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Cross 1989

MethodsRandomised double-blind study. Method of allocation concealment not described.
Doctors and nurses directly involved in pt care did not know identity of solutions.


Participants20 post-op coronary artery bypass patients. Patients with history of significant arrhythmias, congestive heart failure, renal, hepatic, or pulmonary failure were excluded.
Country: USA


Interventions
  1. Hypertonic saline (n=11).
  2. Normal saline (n=9).


for 24 hr period following arrival at ITU.
Study solutions were initially infused at 100 ml/hr, subsequent rates were adjusted according to the clinical status and were infused to maintain hemodynamic stability.


OutcomesDeath.
Hemodynamic variables.


NotesFollow-up 24 hours.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Gunn 1989

MethodsRandomised controlled trial. Method of allocation concealment not described.


Participants51 adult patients who sustained at least 20% body surface area burns and who were admitted within 12 hours of injury.


Interventions
  1. Hypertonic sodium lactate
  2. Ringer's lactate.


Intravenous fluid was administered to maintain the urine output at a target rate of 0.5-1.0 cc/kg/hour, and maintain a minimal or zero base deficit in serial blood gas analyses.


OutcomesHemodynamic variables.
Enteral intake.


NotesFollow-up was for 72 hours. High drop-out rate due to need for surgery, excision and grafting. These patients were not followed up after surgery.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearD - Not used

Jarvela 2002

MethodsRandomised controlled trial. Patients were randomly allocated according to a list of random digits to 2 groups.
Blinding not specified.


Participants72 patients undergoing elective coronary artery bypass graft surgery. Patients were excluded if they had a left ventricular ejection fraction less than 0.4, a serum creatinine more than 130 umol/L, hepatic or renal disease, or continuous medication with diuretics.
Country: Finland.


Interventions
  1. Hypertonic saline (7.5%) (n=36).
  2. Normal saline (0.9%) (n=36).


Both groups received 4ml/kg during 30 minutes, when volume loading was needed during the postoperative warming period in ICU. The infusion was stopped if systemic arterial pressure exceeded 170 mmHg.


OutcomesHemodynamic variables.
MAP.
Cardiac index.


NotesFollow-up first post-op morning.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Jelenko 1978

MethodsRandomised controlled trial, method of allocation concealment not described.
Blinding not mentioned.
No loss to follow up.


Participants12 patients with burns covering more than 20% of body surface.
Country: USA.


Interventions
  1. Hypertonic saline (240MeQ Na+, 120 MeQ Chloride, 120 MeQ lactate) (n=5).
  2. Ringer's lactate (n=7).


Allocated fluid was used, guided by haemodynamic variables, to the end of resuscitation.


OutcomesDeath.
Hemodynamic variables.


NotesFollow-up to the end of resuscitation.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

McGough 1990

MethodsRandomised controlled trial. Method of allocation concealement not described.


Participants50 patients undergoing total hip arthroplasty, hysterectomy, or radical prostatectomy.


Interventions
  1. Hypertonic saline at 4 ml/kg/hr.
  2. Ringers lactate at 8 ml/kg/hr.


OutcomesComplications.


Notes


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Shackford 1983

MethodsPatients were assigned by random number to one of two groups. Allocation was done by list of random numbers read by someone entering the patient into the trial (open list).
No mention of blinding.


Participants58 patients undergoing aortic reconstruction.
Country: USA.


Interventions
  1. Group one received a hypertonic solution (HSL) (n=30).
  2. Group two received ringers lactate (n=28).


Fluid was given to maintain the cardiac filling pressure within 3 torr of the preoperative level and the cardiac output at or above the preoperative level. All pts received 5% dextrose in 0.25N saline as a maintenance solutuion.


OutcomesHemodynamic variables.
Death.


NotesFollow-up three days.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?NoC - Inadequate

Shackford 1987

MethodsPatients were assigned by random number to one of two groups.
Allocation was done by list of random numbers read by someone entering the patient into the trial (open list).
No mention of blinding.


Participants52 patients undergoing aortic reconstruction.
Country: USA


Interventions
  1. Hypertonic lactated saline (n=26).
  2. Ringer's lactate (n=26).


During and immediately after the operation fluid was given to maintain the CO equal to preoperative levels and the cardiac filling pressures within 3 torr of the preoperative value. Post-op all of the patients received 5% dextrose in normal saline as a maintenance solution, this was continued until the first day post-op. During this same period, additional fluid (either HSL or RL) was given to maintain cardiac filling pressures and CO at pre-op levels.


OutcomesHemodynamic variables.
Serum compositional changes.


NotesFollow-up three days.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?NoC - Inadequate

Simma 1998

MethodsRandomized controlled trial. Randomization was done by an independent investigator. Staff were not blinded to the type of fluid.


Participants32 head-injured children under the age of 16 with Glasgow coma scores of <8. The patients entered the study at the time when ICP was first measured.
Country: Switzerland.


Interventions
  1. Hypertonic saline (n=15).
  2. Ringer's lactate (n=17).


Over 72 hours.


OutcomesHemodynamic variables.
Complications.
Length of hospital stay.
Death.


NotesFollow-up until discharge from hospital.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Vassar 1990

MethodsRandomised controlled trial, allocation concealment unclear.
Double blind study (solutions prepared in identical containers).
No loss to follow up.


Participants59 injured patients were entered into the trial. Participants were emergency department admissions with trauma and a systolic blood pressure below 80mm Hg and were 18 years or older.
Pregnant women and people with preexisting cardiac, hepatic or renal disease were excluded.
Country: USA


Interventions
  1. 7.5% saline (n=32).
  2. Ringer's lactate (n=27).


Allocated fluids were given as the initial resuscitation fluid in the emergency department.


OutcomesHaemodynamic variables.
Death.


NotesFollow-up until discharge from hospital.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Vassar 1993a

MethodsRandomised controlled double blind trial. Allocation concealed by random sequence of identical containers.
36 people excluded post randomisation as deemed not to have met eligibility criteria.
No loss to follow up.


Participants169 pre-hosptial trauma patients, who were undergoing ambulance transport to an emergency centre, had systolic blood pressure 90 mmHg or less, and were 18 years or older.
Exclusions: asystolic, undergoing CPR, lack sinus complex on ECG, more than 2 hours after trauma, pregnant, preexisting seizures, bleeding disorder, hepatic, cardiac or renal disease.
Country: USA


Interventions
  1. 7.5% saline (n=85).
  2. 0.9% saline (n=84).


Participants received 250mL of the allocated fluid in the pre-hospital setting. Additional isotonic crystalloids were given as needed.


OutcomesDeaths reported.
Haemodynamic variables.
Trauma scores and neurological outcome scores.


NotesFollow-up until discharge from hospital.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Vassar 1993b

MethodsRandomised controlled trial, allocation concealed by sequential use of coded identical containers. Only the manufacturer could know the treatment assignment.
Double blind study.
39/233 patients excluded as deemed not to meet eligibility criteria, unclear from which groups.


Participants95 pre-hospital trauma patients undergoing helicoptor transport to an emergency centre, had a systolic blood pressure of 100mmHg or less and were 18 years or older.
Exclusions: asystolic, undergoing CPR, lack sinus complex on ECG, more than 2 hours after trauma, pregnant, preexisting seizures, bleeding disorder, hepatic, cardiac or renal disease.
Country: USA


Interventions
  1. 7.5% saline. (n=50)
  2. Ringer's lactate. (n=45)


Participants received 250mL of the allocated fluid in the pre-hospital setting. Additional isotonic crystalloids were given as needed.


OutcomesDeaths reported.
Haemodynamic variables.
Trauma scores and neurological outcome scores.


NotesFollow-up until discharge from hospital.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?YesA - Adequate

Younes 1988a

MethodsRandom assignment. Method of allocation concealment not mentioned.


Participants33 patients admitted to the emergency ward in hypovolemic shock (mean arterial pressure < 60 mmHg)


Interventions
  1. Hypertonic 7.5% saline (n=18).
  2. Isotonic NaCl (n=15).


Both fluids received at infusion rate of 10ml/minute, over 15 minutes. No other fluid was given after the infusion unless MAP fell below 80mmHg, until typed-crossmatched blood was available. Patients were excluded from the study as soon as given fluid or blood.


OutcomesMAP


NotesLength of follow-up not recorded.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Younes 1988b

MethodsRandom assignment. Method of allocation concealment not mentioned.


Participants31 patients admitted for abdominal aorta reconstructive surgery.


Interventions
  1. Hypertonic 7.5% NaCl, (n=18)
  2. Isotonic 0.9% saline (n=13)


Both groups received fluid as the volume of 4ml/kg of body weight, infused during 15 minutes. The infusion was started 2 minutes before the release of the aortic clamp.


OutcomesMAP.
Haemodynamic variables.


NotesLength of follow up not recorded.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

Younes 1992

MethodsRandomised 'in a double blind fashion'.
Blinding by use of similar bottles.
No loss to follow up.


Participants70 emergency department admissions, who had a systolic blood pressure of less than 80mm Hg and were 19 years and older.
Exclusions: pregnant, preexisting cardiac or metabolic disease.


Interventions
  1. 7.5% saline (n=35).
  2. 0.9% saline (n=35).


Allocated fluid was for initial bolus of 250mL, followed by isotonic crystalloids as needed.


OutcomesDeaths reported.
Fluid balance.


NotesFollow-up until discharge from hospital.


Risk of bias

ItemAuthors' judgementDescription

Allocation concealment?UnclearB - Unclear

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Fisher 1992Cross-over study.

Holcroft 1987The study was not randomised. Fluid was administered depending on the attending surgeon.

Shackford 1998Study compared hypertonic fluid versus hypotonic.

Shao 2005The patients were 'assigned' and not randomised.

 
Comparison 1. Hypertonic versus isotonic crystalloid

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Death14Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Trauma
6651Risk Ratio (M-H, Fixed, 95% CI)0.84 [0.69, 1.04]

    1.2 Burns
389Risk Ratio (M-H, Fixed, 95% CI)1.49 [0.56, 3.95]

    1.3 Surgery
5230Risk Ratio (M-H, Fixed, 95% CI)0.51 [0.09, 2.73]

 2 Poor outcome (GOS)1226Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.82, 1.22]

    2.1 Trauma
1226Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.82, 1.22]