POTD: Tamiflu Tuesday

Respiratory season is here in Brooklyn, and with it comes the return of influenza. Just last week, we saw a significant increase (53%) in the number of positive influenza tests compared to the previous week. While the ED volume may make it seem like we’re at the peak, unfortunately, this graph from the New York State Department of Health suggests that we’re only just beginning. 

With the influx of influenza-positive patients into the ED, you may to wonder if there’s anything we can do for them. Tamiflu, also known as Oseltamivir, is a drug that can help alleviate the symptoms of influenza. This drug works by inhibiting the neuraminidase enzyme of the influenza virus, preventing its replication in the body. I personally like this graphic that perfectly summarizes the mechanism of action with a giant red X.

To Tamiflu or not to Tamiflu?

But of course, some things are simply too good to be true and the lore surrounding Tamiflu is rife with controversy.

To make a long story short, Tamiflu first entered the market in 1999 and received substantial support from the CDC and WHO. It even made it onto the World Health Organization’s List of Essential Medicines from 2009 to 2017. This support was based on multiple pharmaceutical-sponsored trials that showed a ~1.5-day reduction in influenza symptoms and a reduction in secondary complications, such as hospitalizations and pneumonia. However, in a shocking turn of events, the pharmaceutical companies (namely Roche) who sponsored these trials didn’t even provide the authors with access to the data but instead simply informed them of the data’s purported findings.

This discovery brought all the data into question. Since then, numerous studies have been conducted to assess the true efficacy of Tamiflu. I’ll list some of these studies below for your review, but the bottom line is that the data supporting Tamiflu’s benefits is, at best, lackluster.

Benefits of Tamiflu:

• Reduces the duration of symptoms by up to 36 hours (but more realistically around 17-24 hours) when started within 48 hours of symptom onset.

• Decreases the likelihood of contracting the flu by approximately 50-80% when used as a post-exposure prophylaxis medication within 48 hours of exposure.

Risks of Tamiflu:

• Nausea, vomiting, diarrhea, and/or headache occur in up to 17% of patients.

• Neuropsychiatric events (including confusion, delirium, hallucinations) have been reported.

• The cost of Tamiflu is around $60 for patients without insurance.

The saga and controversy of Tamiflu could go on much longer, but I’ll wrap it up here.

TLDR: The data for Tamiflu suggests a very modest reduction in the duration of symptoms (only about half to one full day) without a statistically significant reduction in complications such as hospitalizations or pneumonia. There are notable risks, including gastrointestinal distress and reports of neuropsychiatric events in children. Instead just get your flu shot.

Sources:

https://www.health.ny.gov/diseases/communicable/influenza/surveillance/2024-2025/flu_report_current_week.pdf

https://rebelem.com/the-alic4e-trial-oseltamivir-usual-care-vs-usual-care-alone/

https://www.bmj.com/tamiflu

https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/215903

https://first10em.com/tamiflu-doesnt-work/

https://rebelem.com/the-tamiflu-debacle/

Tamiflu Trials:

Jefferson T et al. Oseltamivir for Influenza in Adults and Children: Systematic Review of Clinical Study Reports and Summary of Regulatory Comments. BMJ 2014. PMID: 24811411

Krumholz HM et al. Neuraminidase Inhibitors for Influenza: The Whole Truth and Nothing but the Truth. BMJ 2014. PMID: 24811413

Okoli GN et al. Use of Neuraminidase Inhibitors for Rapid Containment of Influenza: A Systematic Review and Meta-Analysis of Individual and Household Transmission Studies. PLOS One 2014.PMID: 25490762

Qiu S et al. Effectiveness and Safety of Oseltamivir for Treating Influenza: An Updated Meta-Analysis of Clinical Trials. Infectious Diseases 2015. PMID: 26173991

Heneghan CJ et al. Neuraminidase Inhibitors for Influenza: A Systematic Review and Meta-Analysis of Regulatory and Mortality Data. Health Technology Assessment 2016. PMID: 27246259

VOTW: Hepatization of Lung

Here is this week's VOTW:

A 69-year old male with a history of COPD presented to the ED for 1 month of cough and 1 week of hemoptysis. A chest x-ray showed a left lower lobe consolidation vs atelectasis vs effusion. A POCUS was performed to better characterize the area which showed…

Clip 1 and Clip 2 shows "hepatized lung", a large isoechoic area of lung tissue just under the pleura that has a similar echogenecity to the liver which is suggestive of a consolidation. The echogenic jagged line in the far field is the interface between consolidated and aerated lung. Within the consolidation, air bronchograms (scattered echogenic dots and lines) can be seen. 

Findings of pneumonia on lung ultrasound

Hepatization of the lung - Normal lung tissue is not visible on ultrasound as it is filled with air. As pneumonia develops, inflammatory material (fluid, pus) fill the alveoli of the lung, and the affected lung tissue becomes more solid and visible on ultrasound. A large consolidation takes on the appearance of a solid organ like liver and is referred to as “hepatization of the lung”. Atelectasis can also have this appearance.

B-lines are not specific to pulmonary edema and can be see with pneumonia due to the fluid within the alveoli. This may be the only finding in early pneumonia. Focal B-lines are more suggestive of infectious process while diffuse B-lines are more suggestive of pulmonary edema.

Shred sign refers to small hypoechoic lesions abutting the pleura which gives the appearance of a jagged pleural line. This is highly specific for a small subpleural consolidation. The jagged line is the interface between consolidated and aerated lung and not actually the pleural interface.

Air bronchograms (image below) are small pockets of air that are present within the small bronchi within the consolidation seen in both atelectasis and consolidation. Dynamic air bronchograms move in and out along the bronchi with each breath and is more specific for a true consolidation. Static air bronchograms are more suggestive of atelectasis as with complete collapse of the lung air won’t move in or out but can also be seen with consolidation.

Image 1. Air bronchograms

Pleural effusions frequently accompany a pneumonia. Echogenic debris or septations within the effusion can suggest an empyema.

Tips and tricks on Lung Ultrasound

• Use the curvilinear probe using the Lung settings

• Orient your probe with the probe marker towards the head, find two ribs which are hyperechoic with posterior shadowing and identify the shiny shimmering pleura in between

• If looking for B-lines, increase the depth so you can see the b-lines which extend all the way down the screen. This lets you differentiate B-lines from comet tail artifacts which do not extend all the way down the screen and are not pathologic.

• If looking for a pneumothorax, decrease the depth so you can focus at the pleura and more easily look for lung sliding. You can also switch to a linear probe for higher resolution

• When looking for a pleural effusion at the lung bases, bring the vertebral bodies in view so that you can look for a “spine sign” (extension of the spine above the diaphragm which would indicate the presence of a pleural effusion)

Case conclusion

A CTA Chest showed a dense left lower lobe consolidation. The patient was given IV antibiotics and admitted for the management of pneumonia and hemoptysis.

Here is a great review of lung ultrasound for pneumonia: https://litfl.com/lung-ultrasound-pneumonia/

Happy Scanning,

Your Sono Team

VOTW: Lung Point

Hi all, this week's VOTW is presented by Drs Forrest, Yang and Schiller!

A 71 year old male w/ hx of COPD presented to the ED for altered mental status. He was found to be obtunded due to hypercapnia and was intubated in the ED. Several hours after admission to the MICU the patient suddenly desaturated to 64%. 

A POCUS was rapidly performed which showed…

Clip 1 shows a POCUS of the R anterior chest. On the left side of the screen, the pleural line has absent lung sliding. From the right of the screen, normal pleura with lung sliding is seen coming into the image with every breath. This is a “lung point” which is the exact point at which the pneumothorax starts. A chest x-ray confirmed a large R sided pneumothorax with mediastinal shift. A chest tube was placed by the ED team for a tension pneumothorax with improvement in vitals.

Image 1 shows an M-mode image obtained expertly by the team at the lung point which shows both "seashore sign" indicative of normal lung as well as "barcode sign" indicative of pneumothorax in one clip. You'll see this only if you use M-mode at the lung point.

M-mode showing areas of “sandy beach” alternating with “barcode sign” at the lung point

Lung sliding

In normal lung, the pleural line will appear to shimmer due to the movement of the visceral and parietal pleura sliding against each other. With a pneumothorax the contact between the two pleura are lost and the pleural line will appear still. 

*The presence of lung sliding rules out a pneumothorax at the location of the chest you are scanning. 

*Image the least dependent site (where air is most likely accumalate) to maximize sensitivity of the test (anterior chest in a supine patient).

*Reduce your image depth all the way! This way you don't have to squint while looking for lung sliding

Lung point

This is the point at which normal lung sliding and absent lung sliding are seen next to eachother simultaneosuly and is the exact point where the viseral pleural is peeling away from the parietal pleura. If found, this finding is highly specific for pneumothorax. It won't be seen with a large pneumothorax that envelops the entire lung.

Does absence of lung sliding always indicate pneumothorax?

No. Absence of lung sliding can be seen with many conditions including a bleb from COPD, right mainstem intubation (no left-sided lung sliding), patients w/ previous thoracic surgery (such as pleurodesis or VATS), pleural adhesions, ARDS, pulmonary fibrosis, atelectasis, and phrenic nerve paralysis. If the patient is stable, confirm the diagnosis with a chest x-ray or CT prior to placing a chest tube.

Which lung ultrasound artifacts rule out pneumothorax?

A-lines are reverberation artifacts that can be generated by air in normal lung tissue or air in the pleura so cannot be used to rule out pneumothorax.

B-lines indicate the presence of interstitial edema which can only be seen if the lung tissue is abutting the pleura. Even seeing one B-line is enough to rule out pneumothorax.
Happy sliding,

Your Sono Team