Chemotherapy Induced Emetogenecity

Cancer is one of the top three killers today and Emergency Departments are expected to  see more and more Oncological Emergencies in future. CINV i.e. Chemo Induced Nausea and Vomiting is one such complication of chemotherapy. 

Few patients receiving chemotherapy rank CINV as the most severe side effects and in the past, about half of the patients postponed or refused, potentially curative treatments due to the fear of CINV. With the correct use of antiemetics, CINV can be prevented in almost 70% to up to 80% of patients. Though over the past 25 years, steady improvements in the control of chemotherapy-induced nausea and vomiting (CINV) have been achieved but it still remains a significant issue of concern. 

Pathophysiology of CINV

CINV happens due to noxious reactions along the neuronal pathways. Chemoreceptor trigger zone, which is outside the blood-brain barrier senses emetic stimuli through receptors such as 5HT3, NK1, D2 and muscaranic. Chemicals bind to these receptors and initiate a response. Additionally, activation of these receptors may also occur through GI irritation. 

CLASSIFICATION OF CINV

CINV is differentiated into the following categories: 

1. Acute onset: within 24 hours of initial administration of chemotherapy
2. Delayed onset: occurring 24 hours to several days after initial treatment
3. Anticipatory: emetic episodes are triggered by taste, odor sight, thoughts, or anxiety secondary to a history of poor response to antiemetic agents 
4. Breakthrough: occurring despite prophylactic treatment
5. Refractory: occurring during subsequent cycles when antiemetics have failed in earlier cycles

Risk of CINV with Chemotherapy medications 

Patient-related risk factors, including young age, female gender, experience of emesis during pregnancy, impaired quality of life, and previous experience with chemotherapy, are also known to increase the risk for CINV. Conversely, patients with a history of high alcohol consump- tion have a lower risk of chemotherapy-induced nausea and vomiting.

Management

5-HT3RAs (Receptor Antagonists)

• High therapeutic index for prevention of CINV, most effective antiemetics in the prophylaxis of acute CINV. 
• Generally safe, with a favorable side effect profile (low grade headache, malaise, and constipation). High-dose (24-32mg) Ondansetron appears to be more effective  
• Some literature reports suggest a potential link between 5-HT3 receptor antagonists and the serotonin syndrome, QTc prolongation esp with a single IV dose of 32mg

Steroids, Dexamethasone/Methylpresdnisolone 

• Steroids can be effective when administered as a single agent in patients receiving chemotherapy of low emetic potential. Most beneficial, when used in combination with other antiemetic agents.
• When corticosteroids are administered with aprepitant, doses should be reduced by half.

NK1RAs, Aprepitant

• Aprepitant is the first representative of this new group that blocks the NK1 receptor in the brainstem emetic center and gastrointestinal tract
• Aprepitant is a moderate inhibitor of CYP3A4; therefore, the dexamethasone dose has to be reduced if used concomitantly.

Adjunctive therapy 

1. Metoclopramide

• In the past, metoclopramide was used alone or in combination with a corticosteroids
• Now, it is reserved for those who are intolerant to 5-HT3RAs or steroids
• May cause extrapyramidal side effects including acute dystonic reactions, akathisia  

2. Olanzapine  

• An atypical antipsychotic drug with potential antiemetic properties because of its action at multiple receptor sites implicated in the control of nausea and vomiting.

3. Benzodiazepines

• Used in certain circumstances, to cut anxiety and risk of anticipatory CINV or in patients with refractory and breakthrough emesis.

4. Antihistamines

5. Cannabinoids

• Possess beneficial side effects (sedation, euphoria) in addition to weak antiemetic efficacy but usefulness is limited by the high incidence of toxic effects, such as dizziness and hallucinations.
• Advised in patients intolerant or refractory to 5-HT3RAs or steroids and aprepitant. 

Key Points

First Line for CINV - 5HT3 Antagonists, Steroids, NK1RA
Adjuncts - Benzodiazepines, D2 RA, Olanzapine, Anti-Histaminics, Cannabinoids 


References: 

1. Jordan K, Sippel C, Schmoll HJ. Guidelines for antiemetic treatment of chemotherapy-induced nausea and vomiting: past, present, and future recommendations. The oncologist. 2007 Sep 1;12(9):1143-50.
2. WHO Pharmaceuticals newsletter. Ondansetron and serotonin syndrome. 2012; 3:16.
3. Bymaster FP, Calligaro DO, Falcone JF, Marsh RD, Moore NA, Tye NC, Seeman P, Wong DT. Radioreceptor binding profile of the atypical antipsychotic olanzapine. Neuro psychopharmacology. 1996 Feb 29;14(2):87-96.
4. WarrDG, HeskethPJ, GrallaRJetal. Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in pa- tients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 2005;23:2822–2830. 
5. www.uspharmacist.com
6. Hesketh, Paul J. "Chemotherapy-induced nausea and vomiting." New England Journal of Medicine 358.23 (2008): 2482-2494.

Author:

              

     Lakshay Chanana

     @EMDidactic

                                                        

 

PokeMon Emergencies : A Call for Public Health Safety

From the Desk Of:
Sagar Galwankar, MBBS, DNB, FACEE (INDIA), MPH, Dip. ABEM (USA), FRCP (UK)

As I went to work I saw few of my colleagues discussing about this new app called PokeMon GO.

This is a Freely available Video Game played via a downloadable app. 

This allows players to capture digital creatures at real locations synchronized with GPS. The GPS Activated locations are called POKESPOTS and the players can capture and gain points called XP. 

There are various awards and rewards by playing this game. 

This has a lot of implications. 

There is massive Public Frenzy and craze and as I had guessed People are trespassing and many accidents and injuries are anticipated when driving walking as people continue to play  and not pay attention.

A New Era of Public Safety Threat has emerged and reached a whole new level !

I recently read this article: http://www.foxnews.com/tech/2016/07/14/death-by-pokemon-public-safety-fears-mount-as-pokemon-go-craze-continues.html

Were we not glued on enough to the Smart Phone on Social Media and video games ?

Were we not disconnected enough that Messaging became the New means of Communication ?

Were we not lonely enough that animated characters are the new friends ?

Technology can with advances but also came with Public Health Threats.

Smarts Phone created a new platform and era of STAT COMMUNICATIONS and UPTODATE INFORMATION.

That brought the Public Health Threat of Civil Safety as Social Media played an Open Access Platform with information about who is doing what and when.

It also brought to light the Road Safety issues where crashes happened while Texting.

It brought to light the violation of privacy of people in the world.

I believe that Mass Frenzy is a phenomenon which has often been the single most important factor to heightened ignorance and accidents.

Travel on Roads as a Driver/ Rider or Pedestrian, Walking at Home or at work and not focusing on what you do will cause a fall/crash and injuries are more severe than ever.

I have seen patients who have got insomnia as a result of sounds and rings of social media and their addiction to see the phone asap.....like a Pavlov Rat.

This Digital Plantation of Revolutions have brought a new age of humans who have isolated themselves to find solace in their single trusted friend.....their smart phone.

Video Games are the new friends introduced by this trusted friend.

There have been many news which have already started reporting injuries and accidents and I soon think we will have to ask for every car crash / and fall .....Were you playing on the SmartPhone ?

The answer may just be YES.

I think its time that Public Health Social Marketing Strategies highlight the urgency to design initiatives to break this addictive unsafe habits of SmartPhone Mania....so Public Health can be safer than before !

When people's mind is fixated on one thing then that is what drives their lives. 

Texting, trespassing and all the crashes falls and accidents with the above apps proves that these are sane people who are conditioned to commit themselves to this public safety risk and hazards..... this is much bigger than just a Habit.... this is addiction and the single biggest Mental Health Challenge to Public Health.

Author: 

                                                   

Dr. Sagar Galwankar  

MBBS, DNB, FACEE (INDIA), MPH, Dip. ABEM (USA), FRCP (UK)

Chief Academic Officer of the INDO-US Emergency and Trauma Collaborative 

Assistant Professor 

Department of Emergency Medicine 

University of Florida, Jacksonville 

(Follow Dr. Galwankar on Twitter @SagarGalwankar)


Originally published at beepers365.blogspot  on July 15, 2016. Reposted with permission.

Start asking the question - What is causing CONSTIPATION?

Definition
Constipation is defined as either stool frequency of < 3 times per week or difficulty in passing stools. It is a quite frequent presenting complaint in the ED and many of us treat it like a trivial issue. However, there are a few life-threatening conditions which might present with the chief complaint of constipation. Often it is seen in the elderly and those with multiple medical problems, complicating both their assessment and treatment. 

Key Questions:

• What do you exactly mean when you say "I am constipated?" (Dig into the frequency, amount, caliber of stools)
• Associated Symptoms (Tenesmus, Blood in stools, pain while defecating, Weight or Appetite changes, Pain Abdomen, Nausea/Vomiting, Alternating Diarrhea)
• Duration of constipation (Acute v/s Chronic)
• Ask for any neurological disease, thyroid disease, diabetes, spinal cord pathology?
• Medications? (Opioids, Anticholinergics,CCBs, Diuretics, Iron, Aluminium Antacids, NSAIDs)
• Lifestyle (Bed Ridden, Dietary intake of Water and fibre, Sedentary)

Causes of Constipation (Life Threats)

• Bowel Obstruction
• Perforated Viscus
• Bowel Ischemia
• HypoK, HyperCa
• Inflammatory Bowel Disease
• Diverticulitis
• Diet and Lifestyle
• Renal Failure, Hypothyroidism
• Pregnancy 
• Painful lesions (haemorrhoids, fissures)
• Irritable Bowel Syndrome
• Laxative Abuse
• Neuro Disorders (Spinal Cord Disease, Multiple Sclerosis, Parkinson's, Diabetes)
• Medications!

What labs do need to order?

• CBC 
• Electrolytes 
• Renal Function
• TSH
• AXR (suspected bowel obstruction) - Read more on this at LIFTL

Those who look stable, normal vital signs and a BENIGN abdominal exam can be worked up as an out-patient. Treat with laxatives once bowel obstruction had been ruled out. 

Have a "discharge conversation", discuss your concerns and advise on dietary and lifestyle habits and appropriate follow up. 


Take Home

• Start asking the question - What is causing CONSTIPATION?
• Common cause include lifestyle habits, dietary factors and medications
• Faeces seen on plain radiographs is normal. Imaging should be used to exclude other pathologies.
 

Author:

              

     Lakshay Chanana

     @EMDidactic

                                                        

Fostering a culture of appreciation in the ED

The deepest principle of human nature is the desire to be appreciated. Whether it is the CEO of an institute or the housekeeping staff, everyone seeks appreciation for the work that they do. Knowing that our efforts have been recognized and appreciated makes us feel valued. Conversely, without appreciation we can feel taken advantage of, leading to negative reactions. Research suggests that people who feel appreciated are more productive, have greater levels of job satisfaction. Other benefits include more fulfillment, more positive attitudes, decreased stress and burnout.

While teaching children, preceptors make encouraging comments frequently, to make children feel appreciated, reinforce the good behavior and expedite the learning process. Parents praise their children for every effort but this is not done with colleagues at our workplace. Why not? Adults are no different. Self-esteem in kids as well as in adults contains a large component of internalized appreciation. A pat on the back makes individuals feel good and content about themselves and pushes them to achieve more.

This is something that we need incorporate in Medicine (esp. Emergency Medicine). Getting appreciation from colleagues is a rare sight due to a multitude of reasons. But a few words of appreciation can make our day. Also, lack of appreciation is the number-one reason for burn-out and people changing jobs. 

Feeling appreciated is an extremely strong emotion that makes a tremendous difference to relationships. For instance, your rapport with the consulting physician matters a lot when you ask for a consult in the ED. Healthy relationships are in fact build on appreciation. A personalized recognition of someone’s efforts, in a meaningful way to that individual, can make them feel encouraged. It lifts the morale and is a motivation tool that inspires to take that extra effort striving for praise once again. 


Components of Effective Appreciation

• Expressive Action (What you do to express gratitude)
• Inner Attitude (How you felt by a person's actions)

This needs to be done consciously at least in the beginning. People can easily make out the difference between a truly "heartfelt thank you" and an "insincere thank you".


Ways of showing appreciation

1. Saying Thank You - Using words like Please, Sorry and Thank You is important to be courteous towards individuals. But, get rid of the NAKED Thank You. Whenever you express gratitude, tell people about the resulting benefit they created for you and make it more meaningful. Make an extra effort to complete this statement. Don’t just say “THANK YOU”, instead, add the emotion about how you felt and how their act changed things for you. For instance, when you request a colleague to relieve you from work an hour before. Rather than saying an insincere Thank you, consider this

It is very kind of you for being so considerate and showing up early even after working last night. I truly appreciate that. This is going to make things very easy for me today. 

If an attending/ consultant teaches you about a topic following a hectic shift, he just gave you a few minutes of his lifetime. Be thankful to him for doing that.

2. Gifts - The price of the gift is not important here, it is all about the THOUGHT. Everyone likes to enjoy good food. So it is one good way of doing this. You know how it feels, when someone shows up with a box of doughnuts in the midst of a HANGRY (Hungry + Angry) shift! 

3. Publicly acknowledge people for what their work - This makes people feel recognized and also shows others what to aspire to. For instance, if a resident performs a difficult airway, taking 30 seconds and praising him during the next didactic session is going to  make him feel worthy and boost up his confidence. 

This works on the principal of mutuality i.e. the exchanging of actions.  In regard to commendation, that person would be pushed to do more for the former person and aspire for more.

4. Make your appreciation personal - Be specific as it makes people feel being heard, lifted up and understood. Rather than making cliche statements, be clear and candid. Tell them how they impacted your life, what you admire about them. It tells them that you actually spent some time thinking about them.

5. Appreciate yourself - If you have difficulty in praising others then I recommend you to start doing it with yourself first. Perform at least one good deed every day to make you feel appreciated and think what could you do better tomorrow.

6. See what others are doing RIGHT - Rather than focusing on the negative in a person, look at the positive habits. Start acknowledging people regardless of the outcome of the task but recognize the efforts that have put in. 


7. Make “I” statements - It is about how they made you feel, it is not about the other person. So focus on "I" statements. Rather than saying "YOU are awesome", say "I always enjoyed working with you as you constantly checked on my work making me feel secure". Just saying YOU ARE AWESOME is pretty non-specific and meaningless. Using "YOU" statements might make people feel being judged, which is another reason to avoid it.

Further Reading:
Attitude of Gratitude – Showing Some Love in the ED

Author:

              

     Lakshay Chanana

     @EMDidactic