Hypertonic saline dextran (HSD)

[Armymedic]

I have been recently informed that Hypertonic saline dextran (HSD) in 250 ml bags are avail overseas as a Surg Gen controlled item.

This is a great volume expander for trauma and used with the proper procedures and techniques (like FAST IO into the sternum) will significantly assist in resuscitation of hypovolemic patients with controlled hemorrhage.

For those who don't know, HSD is 7.5% saline 6% Dextran 70. It has the capacity to expand intervascular volume 3-5 to 1by pulling intercellar fluid into the blood stream.

Other then it is not yet approved for general used by Health Canada, I do not know why it is a controlled substance.

 

[old medic]

Is it possible it's controlled because it's being used as part of the ongoing fluid resuscitation study?

http://www.toronto.drdc-rddc.gc.ca/publications/factsheets/t31_e.html

.........
Previous clinical trials

Several small clinical trials have demonstrated the safety of hypertonic resuscitation. Recently, a DRDC/CFHS (Canadian Forces Health Services) pilot clinical trial administering hypertonic saline to hemorrhagic shock patients showed marked improvements in inflammatory markers, a 50% decrease in fluid volume required, and a reduction in mechanical ventilation time. Although encouraging, these trials were not large enough to ensure statistically significant survival results.
Project description

CFRIC is an ambitious joint Canadian-U.S. project to conduct multi-centre pre-hospital clinical trials of small-volume hypertonic resuscitation fluids over a 5-year period. It will involve 10 centres (8 US, 2 Cdn) coordinated by a Resuscitation Outcomes Consortium (ROC), led by the National Institutes for Health (NIH) and Canadian Institutes of Health Research (CIHR), and co-funded by US Department of Defence (DoD) and Department of National Defence (DND) of Canada. The specific aims are to:

    * demonstrate efficacy of hypertonic fluids for resuscitation of hemorrhagic patients; and their ability to enhance survival.
    * provide an opportunity for DRDC to perform unique inflammatory analyses.
.......

 

[medicineman]

Basically any substance or item that is Special Access from Health Canada or is designated a shiny item is an SG Controlled Item (or at least so it seems).  Examples are the HI-6, MS and Diazepam auto-injectors (injectors themselves, as well as the actual HI-6).  Oddly enough, vehicle/section trauma packs are as well - but just the jumpbag they come in (though strangely enough, the fully stocked Med Tech jumpbags aren't  :) but not the equipment.

Likely the other reason there is a control on it is to ensure it's used within specific parameters or protocols - wouldn't want to imagine someone using it to treat simple dehydration for instance...

MM

 

[Donut]

BC Amb has recently restarted our HS/HSD/NS double blind clinical study.  It was halted because we hadn't made adequate arrangements for monitoring of the patients at the tertiary care centers, and hadn't included the right to refuse enrollment for conscious trauma patients

It's also being investigated for use in TBI due to the osmotic effects on extracellular fluids.

The restart was preceeded by a small protocol recall study by Clinical Tng to redesign the aide-memoires that accompany each trial pack.

I'm now on leave from the service, and haven't seen the new aide-memoires, so won't comment on those.

 

[kj_gully]

TBI= Traumatic Brain injury? Forgive my ignorance. I am interested in this product, anyone can see how this relates toSARTech operations. We unfortunately are practicing our medicine in Canada on civilians, so unlike the military (and prisons ), don't have a suitable test population. It will be a while until we see this in our jump bags.

 

[Donut]

You got it, Gully.

I'm not surprised you're not using it, but if you're in BC you may see it.  We use it on civies, too ;D, and I should say I was surprised as heck when it first came out and I was told patients didn't have the right to refuse...that's since been amended.

 

[Armymedic]

gully, no offense buddy, but, you just work on dumb civvies...   this is more of a military medicine issue.

I have reservations about this being trialed on civ street for the same reasons. This product should have its own trial in Afghanistan where its use is not only used once Health Canada approved, but very needed currently.

I would love to see every QL5 medic and above trained and approved to use HSD and to use FAST IO with the fluid if indicated for every hypovolemic patient with controled hemmorage. Also, it is more likely they will see TBI in Afghanistan then anywhere in Canada.

Atleast the 1st line medics will hopefull have access to it, and taught how to use it (Unless of course CYA comes into play).

 

[Bigmac]

        I attended a Fluid Resuscitation in Combat seminar at DCIEM in Toronto a few years ago. There were several foreign presenters talking about the benefits of many new IV solutions including isotonic saline with dextran.The most interesting was an Israeli doctor who gave combat examples and successful study results from numerous trauma casualties who were given the saline/dextran product. As far as tests go the Israeli military has been using this product for years. Can we not get the results of the Israeli studies?     
      For the medic out on patrols this would mean only having to lug 250cc IV bags. No offense, but who cares if the civvies get these IVs.  Let's get the product and do our own trials. We all know that what a severely bleeding trauma casualty really needs is blood but anything to keep them hemodynamically more stable until they get to definitive care is a benefit.

 

[Armymedic]

Here is one study done.

http://www.jtrauma.com/pt/re/jtrauma/abstract.00005373-199801000-00005.htm;jsessionid=GJGX557p52mHF64L3PS5zwpPx4T2mfqgfY4tJhbXch1n3z17qtqL!-377544086!-949856144!8091!-1

Effects of Hypertonic Saline and Dextran 70 on Cardiac Contractility after Hemorrhagic Shock.

Article

Journal of Trauma-Injury Infection & Critical Care. 44(1):59-69, January 1998.
Ogino, Ryukoh MD; Suzuki, Kouichiro MD; Kohno, Masahiko MD; Nishina, Masayoshi MD; Kohama, Akitsugu MD
Abstract:
Objective: The effects of a bolus of 7.5% NaCl-6% dextran 70 (HSD) on cardiac contractility were evaluated in anesthetized sheep with hemorrhagic shock.

Background: HSD has been shown to be effective at resuscitation in cases of hypovolemia caused by hemorrhage. Common hemodynamic findings after the injection of HSD in hemorrhagic shock are the restoration of cardiac output, increased blood pressure, and improvement of peripheral circulation. Some mechanisms by which HSD maintains circulation in hemorrhagic shock have been proposed: rapid shift of fluid from intracellular to extracellular space, improved peripheral perfusion, and increased cardiac contractility. Conflicting data exist, however, regarding the positive effect of HSD on cardiac contractility after hemorrhagic shock.

Methods: Hemorrhagic shock was induced by shedding mean blood volume of 31.4 mL/kg, and mean blood pressure was maintained at 50 mm Hg for 30 minutes. The HSD group (n = 6) received HSD (4 mL/kg), and the saline group (n = 6) received normal saline (40 mL/kg) after shock. Cardiac functions were measured in both groups using the left ventricular end-systolic pressure-volume relationship and preload recruitable stroke work during the experimental period: before shock, immediately after the resuscitation, and 2 hours after resuscitation.

Results: Hemodynamic parameters in both groups demonstrated similar changes throughout the experimental period without significant difference between the two groups. Not only the slopes of end-systolic pressure-volume relationship and preload recruitable stroke work but also their placements did not result in any significant differences between the groups.

Conclusion: HSD seems to be an effective resuscitation fluid after hemorrhagic shock because the volume required to maintain circulation is smaller than that of normal saline. Our data, however, show that HSD does not enhance cardiac contractility after hemorrhagic shock.

(C) Williams & Wilkins 1998. All Rights Reserved.

Short story, in an anesthetized sheep with hemorrhagic shock, it took 10x the amount of N/S (40 ml/kg) to equal the effects of HSD (4 ml/Kg). Translate that from carrying 250 ml HSD=2500ml of N/S (250 mg vs 2.5 kgs)

 

[Donut]

I suspect Gully's refering to the fact that he humps his kit pretty far, too.  I know I couldn't do his job, maybe one small aspect of it, but it's the getting to the Pt that'd kill me.

As to it being used on civies, it's being trialed on civies, in a multi-site double blind trial.  I think it's absolutely imperative that we establish not only safety, but efficacy of treatments.  While I'm sure the R3 KAF and it's feeding medical teams see a huge amount of trauma, I don't think they can compare with Toronto, BC, California, Seattle and a host of other trauma systems over multiple years for sheer sample size. Apparently we've enrolled a 100+ in the past 3 weeks between the different sites.

WE SIMPLY DON'T KNOW.

Having said that, I've never seen the Israeli studies...if they've completed a multi-site, multi-year, double blind trial, then what the hell are we doing replicating effort?  Lets analyze their results and use the stuff, if indicated.  A sample of 6 sheep isn't convincing, it's an indicator for more research.


Also, Gully, ref the point on prisons, people in custody are completely excluded from the study.

Edit to add:  In conversation with a fellow paramedic and good friend today, he pointed out that military pers are also routinely excluded from medical trials, as they do not have the same right to refuse treatment that the general public have, which is why anyone in custody is excluded.

Food for thought.

DF

 

[medic45]

One limitation of HSD is that it cannot be administered IO due to the tonicity.  Widespread use of the FAST 1 would still require the carrying of standard isotonic solutions.

If anyone wants a CME a link to the HSD ROC study try:

www.emsonline.net

You can enter with a generic ID of BC01 and a password of BC01.  It is a good little CME on HSD use as it pertains to the ROC.  It is also the Seattle/King County CME web site so there is lots of other interesting prehospital care CME on there.

 

[Armymedic]

One limitation of HSD is that it cannot be administered IO due to the tonicity.  Widespread use of the FAST 1 would still require the carrying of standard isotonic solutions.

Are you sure that was for HSD and not just 7.5% HS?

 

[medic45]

As far as I know it is for both.

Here is a link from JEMS that discusses it briefly:
http://www.jems.com/columnists/eagles/articles/17032/

There have been a few limited animal studies that have shown HS/HSD to be effective with IO access but as far as I know there have been little if any human trials showing safety of administration with IO access.
If anyone has any more info feel free to jump in. When I have some time I'll do a little more detailed pubmed search.

The North American ROC trauma study specifically lists IO access as a contraindication for HS and HSD fluid administration due to too many unknowns.

 

[Armymedic]

As part of the Biochemistry portion of the PA course, we have to complete a written assignment discussion how the chemistry of a substance works on the body. My subject was HSD.

If anyone has a question as to how it works, and how its excereted, just ask...

Once my assignment is returned, I will try to post it here.

 

[Armymedic]

as promised:

 

[david_wright]

Well written paper.

I have a couple of questions for anyone who would care to answer:

• 
  What is the incidence of acidaemia due to the chloride in the HSD? I imagine the risks of acidaemia would be quite high, given that the concentration of Cl anions in HSD is also high.
  What is the effect of the dextrans on coagulability, influence on DIC and potential allergic sequelae?
  Finally, the article by Bala Venkatesh and by Holcroft (the first and final articles in your reference page), could you tell me the journal they came from. They pique my interest and I'd like to read them.

Many thanks.

 

[Armymedic]

Thanks.
Your questions are a level or two above my pay grade. Answering (or at least trying to) in reverse order.

All my references were of the net, accessed through Google searches. If I remember correctly, I found much by cross referencing and searching the authors.

The Dextran was found to have a min effect on coagulation itself, as oppose to the effect of the increased blood volume later. Proper use protocols are that bleeding is to be controlled first, so used correctly in the field decreased coagulation do to dilution is not an issue to the pre-surgery caregivers.

I never saw anything referring to sensitivity to HSD in my wider research either.

Acidosis.... not sure. Theoretically, it should increase, but I do not recall reading that. I would guess that it is insignificant due to fluid shifting, and also negated by other homeostatic and caregiver interventions. My level of training and study has not covered acid base balances in depth yet....get back to you on that hypothesis?

DIC...I would assume because of better perfusion, the risk is decreased. As you know all trauma interventions are geared toward prevention of that deadly triad (hypothermia being the third). I do recall reading of hearing, though, that overuse of HSD (3 or more doses of 250 ml) has a correlated increased morbidity, but the speculation there is the survivability of the casualty regardless of treatment.

I am sorry I can't answer your questions better.

 

[david_wright]

Thanks Prairie Dog,

Those questions weren't all meant for you but I thank you for answering them. Upon further reflection, I imagine that the dextrans would, in the setting of the volume being given, pose minimal effect on clotting. My understanding is that the recommendation for dextran administration is 500-1000mL up to a maximum of 20mL/kg/day of dextran 70. The 250mL would therefore, pose little problem although I couldn't find any reference to back that up.

The point you make about DIC is a good one, and indeed one should be more cautious about hypothermia/acidosis. Whilst I cannot be 100% sure, my recollection is that whilst prolonged administration of 0.9% NaCl solutions can lead to acidaemia, the effects of a smaller volume with a higher chloride content is unknown. Perhaps the volume has as much (maybe more) to do with the development of acidaemia.

Thank you for your prompt replies. It is much appreciated.

David

 

[Armymedic]

My understanding is that the recommendation for dextran administration is 500-1000mL up to a maximum of 20mL/kg/day of dextran 70. The 250mL would therefore, pose little problem although I couldn't find any reference to back that up.

The protocol is 2x 250 ml dose of HSD, followed by isotonic fluids. The Holcroft study I referenced speaks of decreased effectiveness will any more doses than that. Other sources concur.

 

[david_wright]

Sorry Prairie Dog, my comments about the administration was in reference to dextrans in general and were i no way meant to represent any official protocol. I can't speak for the protocols you follow, and have never seen any myself as we don't carry it here in the hospital (in Australia).