Category Archives: Complications

Complications, Thorax

Retained Hemothorax Part 2: Lytics (again)

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In my last post, I reviewed a small case report that was published a couple of years ago on lytics for treatment of retained hemothorax. But surely, there must be something better, right?

After digging around, I did find a paper from 2007 that prospectively looked at protocolized management of retained hemothorax, and its aftermath. It was carried out at a busy Level I trauma center over a 16 month period.

All patients with a hemothorax treated with chest tube received daily chest x-rays. Those with significant opacification on day 3 underwent CT scan of the chest. If more than 300 cc of retained blood was present, the patient received streptokinase or urokinase (surgeon preference and drug availability) daily, and rolled around in bed for 4 hours to attempt to distribute it. The chest tube was then unclamped and allowed to drain. This was repeated for 3 days, and if there was still opacification, a repeat CT was obtained. If the volume was still greater than 300 cc, the cycle was repeated for the next 3 days. If the opacification cleared at any point, or the repeat CT showed less than 300 cc, the protocol was stopped and the chest tube removed. If the chest was still opacified after 6 days, VATS was offered.

Here are the factoids:

  • A total of 203 patients with hemothorax were admitted during the study period and 25 (12%) developed a retained hemothorax
  • While a few had treatment start within 4 days, the majority did not receive lytics until day 9 (range 3  –30 days!)
  • The average length of time in hospital after start of lytics was 7 days, leading to a total length of stay of 18 days
  • 92% of patients had “effective” evacuation of their retained hemothorax, although 1 had VATS anyway which found only 100 cc of fluid
  • 16 patients had “complete” evacuation, and 5 had “partial” evacuation
  • There were no hemorrhagic complications, but one third of patients reported significant pain with drug administration

Bottom line: Sounds good, right? The drug seems reasonably effective, although lengths of stay are relatively long. However, streptokinase and urokinase are no longer available in the US, having been replaced with tissue plasminogen activator (tPA). This paper does a cost analysis of lytics vs VATS and found that the former treatment cost about $15000 (drug + hospital stay) vs $34000 for VATS. However, a big part of this was that the drug only cost about $75 per dose. tPA is much more expensive.

So once again, small series, longer lengths of stay, but at least nicely done. Unfortunately, the drug choice is no longer available so use of tPA tilts the balance away from lytics. 

Reference: Intrapleural Thrombolysis for the Management of Undrained Traumatic Hemothorax: A Prospective Observational Study. J Trauma 62(5):1175-1179, 2007.

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Complications, Thorax

Retained Hemothorax Part 1: Lytics

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In my last pair of posts, we reviewed chest tube management. Now let’s dive into hemothorax. This gets a little complicated, because a chest tube doesn’t always do what it’s supposed to when it comes to blood and possible blood clots.

Hemothorax is a common complication of chest trauma, occurring in about one third of cases. It is commonly treated with a chest tube, which usually takes care of the problem. But in a few cases some blood remains, which can result in an entrapped lung or empyema.

There are several management options. Historically, these patients underwent thoracotomy to peel out the fibrinous collection stuck to lung and chest wall. This has given way to the more humane VATS procedure (video assisted thoracoscopic surgery) which accomplishes the same thing using a scope. In some cases, another tube can be inserted, sometimes under CT guidance, to try to drain the blood.

So what about lytics? It’s fibrin, right? So why not just dissolve it with tissue plasminogen activator (tPA)? There have been very few studies published over the years. The most recent was in 2014. I’ll review it today, and another tomorrow. Finally, I’ll give you my thoughts on the best way to deal with retained hemothorax.

Here are the factoids:

  • This was a single center, retrospective review of data from 1.5 years beginning in 2009
  • A total of seven patients were identified, and most had hemothorax due to rib fractures. Three presented immediately after their injury, 4 were delayed.
  • Median time from injury to chest tube placement was 11 days
  • Median time the chest tube was in place was 13 days, with an average hospital stay of 14 days
  • Patients received 1 to 5 treatments, averaging 24mg per dose
  • There was one death in the group, unrelated to TPA treatment
  • No patient “required” VATS, but one underwent thoracotomy, which turned out to be for a malignancy

Bottom line: The authors conclude that tPA use for busting retained hemothorax is both safe and effective. Really? With only seven patients? The biggest problem with this study is that it uses old, retrospective data. We have no idea why these patients were selected for tPA in this 5-year old cohort of patients. Why did it take so long to put in chest tubes? Why did the chest tubes stay in so long? Maybe this is why they were in the hospital so long?

Plus, tPA is expensive. A 100mg vial runs about $6000. Does repeatedly using an expensive drug and keeping a patient in the hospital an extra week or so make financial sense? So it better work damn well, and this small series doesn’t demonstrate that.

Tomorrow, I’ll look at the next most recent paper on the topic, from way back in 2004.

Reference: Evaluation of chest tube administration of tissue plasminogen activator to treat retained hemothorax. Am J Surg 267(6):960-963, 2014.

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Complications, Pharmacy

Salmon Calcitonin After Spine Fractures?

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In my last post, I reviewed some data on the effectiveness of starting Vitamin D supplements after a patient sustains a fracture. The idea was that they might start building better bone and heal their fractures more readily if they boost their D levels. Unfortunately, this was not shown to be true.

Vitamin D improves bone health by facilitating absorption of calcium from the gut. This is a bit indirect and relies on sufficient intake of calcium and good hormonal regulation that directs osteoblasts to incorporate the mineral into bone. Why not work with those hormones directly to try to increase the amount of calcium that is deposited?

Calcitonin is a peptide hormone that has two major effects on calcium levels: it inhibits osteoclast activity that is breaking down bone and releasing calcium from it, and it inhibits calcium reabsorption in the kidneys which causes more to be excreted in the urine.

Perhaps giving calcitonin after sustaining a fracture might improve healing. Many orthopedic surgeons and neurosurgeons swear by this drug. Unfortunately, there are very few randomized, controlled studies of its use for this indication. A meta-analysis was performed that examined both utility and cost-effectiveness that I found interesting.

Here are the factoids:

  • There was some mild evidence that nasal calcitonin was effective in preventing vertebral fractures
    • One paper showed a benefit when giving 200 IU of intranasal salmon calcitonin daily over a 5 year period
    • But a benefit was not shown if 100 or 400 IU were given (this is weird)
    • A marker of bone turnover showed equal reduction in 200 and 400 IU groups (why isn’t this less in the 200 IU group?)
  • Financial analysis showed that it was only marginally cost effective
  • Current retail pricing is about $125 for a month supply
  • Mild side effects like runny nose and nausea are common
  • Intranasal calcitonin has been shown to reduce pain during healing of vertebral fractures

Bottom line: What does all of this mean? First, salmon calcitonin might decrease the number of future vertebral fractures. I say might because only the 200 IU dose in the study showed this effect. I can see where higher doses might be more effective to a point, but having only the middle dose show up as effective is just odd and makes me worry about the study.

The data does seem compelling that taking this product decreases pain during fracture healing. A meta-analysis of this showed that the effect probably only lasts up to a month. 

And finally, from a cost-effectiveness standpoint for avoiding future fractures, this medication is marginal. Luckily, it is relatively cheap at $125 retail and about $25 with insurance in the US. 

Wrapping it all up, intranasal salmon calcitonin might reduce fracture pain for a month and might decrease the likelihood of future vertebral fractures. However, the data are weak enough that cost-effectiveness is borderline. And there are more effective (and cheaper) analgesics available.

The absolute best way to strengthen bones is to exercise, especially engaging in weight-bearing activities. Not only does this strengthen bones, it also increases overall fitness and health. In general, medications are not the way to go to strengthen bones. It took decades for your patient to become osteoporotic. And while these drugs might improve their bone density slowly, a graduated and supervised exercise regimen is probably the best thing you can do for them.

References:

  • Efficacy of calcitonin for treating acute pain associated with osteoporotic vertebral compression fracture: an updated systematic review. CJEM 2020 May;22(3):359-367.
  • A Randomized Trial of Nasal Spray Salmon Calcitonin in Postmenopausal Women with Established Osteoporosis: the Prevent Recurrence of Osteoporotic Fractures Study. PharmacoEconomics, 2001, Vol.19 (5), p.565-575.
  • A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D. Bone 2016 Oct;91:122-9.
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Complications, Extremity

Giving Vitamin D After Fracture: Helpful Or Not?

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The role of Vitamin D in fracture healing is well known. So, of course, trauma professionals have tried to promote Vitamin D supplementation to counteract the effects of osteoporosis. A meta-analysis of of 12 papers on the topic relating to hip and other non-vertebral fractures showed that there was roughly a 25% risk reduction for any non-vertebral fractures in patients taking 700-800 U of Vitamin D supplements daily.

Sounds good, right? So what about taking Vitamin D after a fracture occurs? Seems like it should promote healing, right? A large meta-analysis in an orthopedics journal looked at this very question.

Unfortunately, there was a tremendous variability in the interventions, outcomes, and measures of variance. All the authors could do was summarize individual papers, and a true meta-analysis could not be performed.

Here are the factoids:

  •  81 papers made the cut for final review
  • A whopping 70% of the population with fractures had low Vitamin D levels
  • Vitamin D supplementation in hospital and after discharge did increase serum levels
  • Only one study, a meeting abstract which has still not seen the light of day in a journal, suggested a trend toward less malunions following a single loading dose of Vitamin D

Bottom line: Vitamin D is a great idea for people who are known to have, or are at risk for, osteoporosis and fractures. It definitely toughens up the bones and lowers the risk of fracture. However, the utility of giving it after a fall has not been shown. Of the 81 papers reviewed, none showed a significant impact on fracture healing. The only good thing is that Vitamin D supplements are cheap. Giving them may make us think that we are helping our patient heal, but it’s not. 

What about the use of calcitonin for preventing future fractures? Find that in my next post!

References:  

  • What is the role of vitamin D supplementation in acute fracture patients? A systematic review and meta-analysis of the prevalence of hypovitaminosis D and supplementation efficacy. J Orthopaedic Trauma 2016 Feb;30(2):53-63.
  • Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA 293(18):2257-2264, 2005.
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Complications

TXA, Thromboembolic Events, And Mortality

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I’ve visited several hundred trauma centers over the past 25 years, and recently I’ve begun to appreciate that there are two camps  when it comes to the use of tranexamic acid: the TXA believers and the TXA hesitant.

There have been a number of large studies that seem to suggest a benefit with respect to survival from major hemorrhage, particularly if given soon after injury (CRASH-2, MATTERs). This drug is dirt cheap and has been around a long time, so it has a clearly defined risk profile.

However, many of those hesitant to use it point to the possibility of thromboembolic events that have been sporadically reported. Several years ago, I did my own literature review and found that the number of thrombotic events from TXA was nearly identical to that of transfusing plasma.

JAMA Surgery just published a large systematic review, meta-analysis, and meta-regression that sought to examine the association between thromboembolic events (TE) in patients of any age and involving all medical disciplines, not just trauma.

The anesthesia group at the University Hospital Frankfurt in German did a systematic search of the Cochrane Central Register of Controlled Trials, as well as MEDLINE, for randomized controlled trials involving TXA. They covered all published studies through December 2020.

The authors adhered to standard guidelines for conducting reviews and meta-analysis (PRISMA). They specifically searched for outcomes involving TEs, such as venous thromboembolism, myocardial infarction or ischemia, limb ischemia, mesenteric thrombosis, and hepatic artery thrombosis. They also tallied the overall mortality, bleeding mortality, and non-bleeding mortality.

Here are the factoids:

  • A total of 216 eligible trials were identified that included over 125,000 patients (!)
  • Total TEs in the TXA group were 1,020 (2.1%) vs 900 (2.0%) in the control group
  • Studies at lowest risk for selection bias showed similar results

Bottom line: The authors concluded that IV TXA, irrespective of the dose, does not increase the risk of thromboembolic events. Period.

Hopefully, this is the final study needed to convince the TXA hesitant that it is safe to administer. They may still argue the efficacy, but at less than $100 per vial it is becoming impossible to ignore.

Reference: Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality A Systematic Review, Meta-analysis, and Meta-regression. JAMA Surgery 156(6):3210884, 2021.

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