# Presentation: 219459

## The risk of Severe DIAR in Trauma Patients given HSD

- Eileen M. Bulger, MD
- Associate Professor of Surgery
- Co-PI Resuscitation Outcomes Consortium

## Hypertonic Saline Dextran

- 7.5% saline/6% dextran-70, 250cc given as initial resuscitation fluid for patients with hypovolemic shock
- Approved in 14 European countries, Rescueflow, Biophausia Inc, Sweden
- 8 previous clinical trials,meta-analysis demonstrates improved survival OR 1.47 and 2 fold increase in survival for patients with traumatic brain injury1,2

## Advantages of HSD Resuscitation3

- More rapid restoration of perfusion with small volume
- Improved cerebral perfusion while decreasing intracranial pressure
- May alter the response of the immune system after injury:
- Decrease the risk of developing lung injury (ARDS) by inhibiting neutrophil and monocyte activation
- Reduce nosocomial infection by enhanced T cell function

## Current & Proposed Trials

- Current trial at University of Washington
- Phase 2 trial, primary endpoint ARDS
- Current enrollment 205pts, now on clinical hold
- Proposed ROC trial
-  Phase 3 trial, n=3018
- Hypovolemic shock- 28 day survival
- Traumatic Brain Injury- Neurologic outcome

## Resuscitation Outcomes Consortium

- NIH
- NHLBI
- NINDS
- CIHR
- US DOD
- Canadian DOD

## Limitations of Prior reports of DIAR

- Elective surgery, older population (mean age 60yrs), high rate w/ epidural or spinal anaesthesia
- Relies on comparison to historical controls from 1970-1979
- No randomized controlled trial data available

## Risk of Severe DIAR in Trauma patients

- Experience with HSD
- 900 pts in clinical trials, 20,100pts treated in Europe
- NO REPORTS OF DIAR
- 0/21000,  < 5/100,000
- Estimates based on Hypertonic hetastarch experience: 4-8/100,0004.5

## Comparison of Risk for Severe DIAR

| Trauma pts receiving HSD | 0-4/100,000 |
| --- | --- |
| Historical controls: Ljungstrom et al6,7 | 25-50/100,000 |
| Historical controls:
Ring et al8 | 8/100,000 |
| Promit premedication (20cc) Ljungstrom et al9,10 | 1.4-3/100,000 |
| Annual anaphylaxis risk in community11 | 21/100,000 |

## Why Trauma patients may be protected?

- High circulating levels of catecholamines
- Rapid infusion of the solution may result in an excess of antigen in the blood and thus prevent the formation of immune complexes.

## Limitations of Promit

- Side effects: 1-57/100,0009,10
- Skin reactions
- Bradycardia +/- hypotension
- Hypotension
- HSD most effective as first fluid given
- Premedication may delay medic from other critical interventions
- Feasibility in prehospital or battlefield setting
- Immuno-modulatory effects of Promit are unknown. May interfere with the effectiveness of HSD

## Summary

- Trauma patients receiving HSD at much lower risk of severe DIAR than previous reports.
- To date no reports of DIAR with 21,000 patients receiving HSD.
- There is no statistical difference between the estimated risk of severe DIAR for trauma patients receiving HSD and the projected risk with Promit pre-treatment for dextran infusion.
- We ask the committee to consider whether Promit premedication should be required in this circumstance.

## References

- Wade C, Grady J, Kramer G. Efficacy of hypertonic saline dextran (HSD) in patients with traumatic hypotension: meta-analysis of individual patient data. Acta Anaesthesiol Scand Suppl 1997;110: 77-9
- Wade C, Grady J, Kramer G et al. Individual patient cohort analysis of the efficacy of hypertonic saline/dextran in patients with traumatic brain injury and hypotension.1997 J Trauma 42:S61-5
- Svensen C, Hypertonic Solutions: an update. ITACCS 2002, 6-12
- Schimetta W, Schochl H, Kroll W et al. Safety of hypertonic hyperoncotic solutions-a survey from Austria. Wien Klin Wochenschr 2002, 114:89-95.
- Barron ME, Wilkes MM, Navickis RJ. A systematic review of the comparative safety of colloids. Arch Surg 2004, 139:552-563
- Ljungstrom KG, Renck H, Standberg K et al. Reactions to dextran in Sweden 1970-1979. Acta Chir Scand 149: 253-262, 1983.
- Hedin H, Ljungstrom K. Prevention of dextran anaphylaxis: ten years experience with hapten dextran. Int Arch Allergy Immunol 1997, 113:358-359.
- Ring J,Messmer K. Incidence and severity of anaphylactoid reactions to colloid volume substitute. Lancet, 1977466-469.
- Renck H, Ljungstrom K, Hedin H et al. Prevention of dextran-induced anaphylactic reactions by hapten inhibition. Acta Chir Scand 149:355-360, 1983.
- Ljungstrom K, Willman B, Hedin H. Hapten inhibition of dextran anaphylaxis. Nine years of post-marketing surveillance of dextran 1. Ann Fr Anesth Reanim 12:219-222, 1993.
- Yocum MW, Butterfield JH, Klein JS et al. Epidemiology of anaphylaxis in Olmsted County: a population-based study. J allergy Clin Immunol, 1999 104:452-457