Recombinant Factor VIIa was initially approved for bleeding in hemophiliac patients back in 1999. Over the years, there has been a big move toward off-label use. There appeared to be obvious utility in using it as an emergency hemostatic agent in trauma patients. But as with many new drugs and devices, early enthusiasm slowly gave way to more balanced judgment. Reviews during the past few years are less glowing than they were early on. So what’s really been happening over the past decade?
Researchers at Stanford tapped into a large database of patient level records from 600 hospitals around the US. They identified over 18,000 uses of Factor VIIa during a 9 year time period. By the end of the study period (2008), 97% of use was off-label! Approved use (hemophilia) increased 4-fold, while off-label use increased by 140-fold. Cardiovascular surgery and trauma tied in their amount of off-label use (both about 29% of the sample).
Does it do any good? This paper can’t directly address that question, since it does not have a good comparison group. However, looking at in-hospital mortality is revealing. Use for hemophilia (FDA approved) results in a 4% mortality rate. For trauma, the in-house mortality is 33%. The worst outcomes were with patients with an aortic aneurysm (55% mortality).
Bottom line: This review details the administration of about $175 million worth of recombinant Factor VIIa over 9 years. Off-label use has skyrocketed despite a dearth of good reports that it actually saves lives. The Number Needed to Treat to prevent one additional bad outcome keeps getting larger with every study published. With a price tag of nearly $10,000 per dose, it’s getting harder to justify using it. I think we are seeing the beginning of the end (at least in trauma) for this powerful drug.
Reference: Off-label use of recombinant Factor VIIa in US hospitals: analysis of hospital records. Annals of Int Med 154(8):516-522, 2011.
Eight months ago I blogged about inline stabilization vs inline traction of the cervical spine. Click here to read the post. A reader recently asked what the optimal method for inline stabilization is.
We’ve been pondering this question for nearly 30 years. In 1983, trauma surgeons at UCLA looked at a number of devices available at that time and tested them on normal volunteers. They measured neck motion to see which was “best."
Here’s what they found:
Soft collar – In general, this decreased rotation by 8 degrees but insignificantly protected against flexion and extension. Basically, this keeps your neck warm and little else.
Hard collars – A variety of collars available in that era were tested. They all allowed about 8% flexion, 18% lateral movement, and 2% rotation. The Philadelphia collar allowed the least extension.
Sandbags and tape – Surprisingly, this was the best. It allowed no flexion and only a few percent movement in any other direction.
The Mayo clinic compared four specific hard collars in 2007 (Miami J, Miami J with Occian back, Aspen, Philadelphia). They found that the Miami J and Philadelphia collars reduced neck movement the best. The Miami J with or without the Occian back provided the best relief from pressure. The Aspen allowed more movement in all axes.
And finally, the halo vest is the gold standard. These tend to be used rarely and in very special circumstances.
For EMS: Rigid collar per your protocol is the standard. In a pinch you can use good old tape and sandbags with excellent results.
For physicians: The Miami J provides the most limitation of movement. If the collar will be needed for more than a short time, consider the well-padded Occian back Miami J (see below).
Efficacy of cervical spine immobilization methods. J Trauma 23(6):461-465, 1983.
Range-of-motion restriction and craniofacial tissue-interface pressure from four cervical collars. J Trauma 63(5):1120, 1126, 2007.
Re-expansion pulmonary edema is an uncommon event after chest tube insertion. Typically, patients have had symptoms of pneumothorax for several days, usually 3 or more. It occurs most often if a large amount of air (or blood) is evacuated at once. The patient will typically become symptomatic within an hour, with decreased oxygen saturation and subjective breathing difficulty.
Although the mechanism is not entirely clear, it appears that the small blood vessels in the lung become more permeable if they are collapsed for an extended period. Mechanical stress from rapid re-expansion further damages the vessels, allowing them to leak. This leads to oxygenation and ventilation problems if severe.
Check the history. Most of these patients have had their pneumothorax for 3 or more days.
Check the xray. Complete pneumothorax (or large hemothorax) puts the patient at high risk.
Modify your chest tube insertion technique. Clamp the distal end of the tube so the pneumothorax is not evacuated suddenly as the tube goes in.
Modify the collection system. Do not use suction initially; only set up for water seal. Clamp the tubing on the patient side. Every 10-15 minutes release the clamp and briefly let some of the air out of the chest, then reclamp. Repeat this until all air has bubbled through the water seal chamber.
Watch your patient. If they cough excessively, start to desaturate or become dyspneic, get your respiratory adjuncts. Give higher inspired oxygen by appropriate means, and consider BiPap or CPAP. In extreme cases intubation may be needed. If the patient does not have any difficulties after about an hour, connect the collection system to suction and proceed as you normally would.
Reference: Reexpansion pulmonary edema. Ann Thoracic Cardiovasc Surg 14:205-209, 2008.
EMS in the field and physicians in the ED are faced with rapidly assigning some degree of stability to the patients they treat. What exactly are the shades of stability, and what considerations are there for each degree?
In my mind, there are three levels of “stability”:
Unstable – this one is easy to figure out. The patient has obvious physiologic compromise, which may be objective (low blood pressure, low GCS or poor neuro exam, etc) or subjective (just plain looks bad). EMS: These patients need transport to an appropriate level trauma center (I or II) immediately. If they need airway control or IV access that can’t be obtained in the field, stop at the nearest Level III or IV for assist, then continue on your way FAST. ED: These patient must be a trauma activation. If not activated as your top-tier trauma, activate or upgrade now! These patients must be seen by a trauma surgeon immediately, and can only go to the OR. No diagnostics outside the resuscitation room are allowed unless they can be converted into one of the two stability levels below.
Stable – this one is usually easy to figure out, too. These patients look good, have good vitals, and a low to moderate energy mechanism for their trauma. Look out for those few patients that may be hiding something like moderate bleeding into some body cavity. EMS: Follow your usual transport protocols to select the closest, appropriate hospital. ED: Follow your standard protocols for trauma activation if needed. Transport for standard imaging is fine.
Metastable – this is a term I invented. It describes patients who have evidence of ongoing volume loss that can be controlled with infusion of crystalloid and/or blood products. It is possible to maintain a certainly level of stability using higher than normal volume infusions. This allows physicians to consider diagnostics or interventions outside of an OR. EMS: Ensure adequate IV access and give fluids and/or blood per your local protocols. Transport to a Level I or II trauma center as quickly as possible. ED: Activate or upgrade to your highest level of trauma activation. The trauma surgeon needs to be present to help direct diagnostics or interventions. These patients may go to CT, IR or other appropriate areas with nurse and physician accompaniment to diagnose and possibly treat bleeding. If the patient changes to unstable at any point, they must immediately be taken to the OR.
I am interested in other opinions on this as well. Please post your comments!