Proton Pump Inhibitors and Anti-emetic Cocktail - A remedy for all

A blend of Proton Pump Inhibitor and anti emetics is something that a bulk of patients get, sometimes without a reason. I think it is time to step back and always question ourselves prior to ordering these medications. More importantly, we need to get rid of the thought that pushes us to prescribe thinking that "if there is no benefit, they are probably not going to hurt". Let us look at some possible downsides of these drugs. 

Proton Pump Inhibitors

They are used for a myriad of concerns such as headache, vomiting, nausea, abdominal pain (regardless of presumed etiology), eradicate H. Pylori, ZE Syndrome, gastroenteritis, GERD and so on.. While a single dose may not have much side effects but in the long run, there are potential downsides that might accompany these medications. In addition, these are freely available as over the counter preparations and therefore, have the possibility of being misused. 

Possible Adverse Effects with long term use (other than GI Distress and Headache)

1. Hypocalcemia, Osteoporosis and Fractures Probably because dietary calcium absorption is dependent upon an acidic environment in the gut.

2. Hypomagnesemia (May present as arrhythmias)

3. Anemia (B12 and Iron deficiency)

PPIs may also affect vitamin B12 levels because the body can’t absorb the vitamin without stomach acid to uncouple the vitamin from protein in food. 

It is unlikely that patients with normal iron stores will develop iron deficiency anemia from PPI use alone. However, patients with low baseline iron stores may be more susceptible to further iron depletion with concurrent PPI therapy.

4. Increased risk of infections (Pneumonia and Clostridium Difficle)

PPIs blunt the gastric acid secretion that act as a defense mechanism against enteric bacteria. Increased gastric pH during PPI use allows for colonization of opportunistic microbes) 

5. Alters the composition of gut flora 

6. Interact with Clopdrogel (click here to read more on this interaction)

PPI therapy in combination with clopidogrel (Plavix) use may increase the risk of cardiac events.

Ondansetron (AKA Emeset, Zofer, Zofran)

It is a 5HT3 receptor antagonist that is frequently used for Postoperative and Chemo  Induced Nausea Vomiting , also prescribed for N&V in general and gastroenteritis. It is metabolised by liver.

Concerning Adverse Effects

1. QT prolongation
2. Headache, Dizziness, Fever 
3. Rash, Bronchospasm
4. Diarrhoea/Constipation
5. Serotonin Syndrome (with concomitant use of serotonergic meds)

References:

1  Hutchinson C, Geissler CA, Powell JJ, Bomford A. Proton pump inhibitors suppress absorption of dietary non-haem iron in hereditary haemochromatosis. Gut. 2007;56(9):1291–1295.

2  Ito T, Jensen RT (2010). "Association of long-term proton pump inhibitor therapy with bone fractures and effects on absorption of calcium, vitamin B₁₂, iron, and magnesium". Current Gastroenterology Reports 12(6): 448–57. 

3  Focks JJ, Brouwer MA, van Oijen MG, Lanas A, Bhatt DL, Verheugt FW (2013). "Concomitant use of clopidogrel and proton pump inhibitors: impact on platelet function and clinical outcome- a systematic review". Heart 99(8): 520–7. 

4   Cardoso RN, Benjo AM, DiNicolantonio JJ, Garcia DC, Macedo FY, El-Hayek G, et al. (2015). "Incidence of cardiovascular events and gastrointestinal bleeding in patients receiving clopidogrel with and without proton pump inhibitors: an updated meta-analysis". Open Heart 2 (1): e000248. 

5   Lambert AA, Lam JO, Paik JJ, Ugarte-Gil C, Drummond MB, Crowell TA (2015). "Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis". PLoS ONE 10 (6): e0128004. 

6  Corleto VD et al. Proton pump inhibitor therapy and potential long-term harm. Current Opinion in Endocrinology, Diabetes and Obesity. 2014 February;21(1):3-8. doi:10.1097/MED.0000000000000031 PMID 24310148

7   US Food and Drug Administration. (2012). FDA Drug Safety Communication: New information regarding QT prolongation with ondansetron (Zofran). Retrieved from http://www.fda.gov/Drugs/DrugSafety/ucm310190.htm

8  Gollapudy, Suneeta, Vikram Kumar, and M. Saeed Dhamee. "A case of serotonin syndrome precipitated by fentanyl and ondansetron in a patient receiving paroxetine, duloxetine, and bupropion." Journal of clinical anesthesia 24.3 (2012): 251-252.

Pituitary Apoplexy

Introduction

Pituitary apoplexy (apoplexy: a sudden neurologic impairment) is a neurosurgical and endocrine emergency that constitutes a clinical syndrome caused by the rapid expansion of a pituitary adenoma secondary to ischemia and /or intratumoral hemorrhage which causes compression of the cavernous sinus, chasm,  optic nerves and hormonal imbalance. The diagnosis is often delayed as approximately ~80% of these patients will have no previous history of a pituitary problem. Pituitary apoplexy may also occur in non-adenomatous or even the normal pituitary gland especially during pregnancy. 

Most cases of pituitary apoplexy present in the fifth or sixth decade with a slight male preponderance and the most common presenting symptoms is sudden severe headache, which is frequently retro-orbital in location.

Pathophysiology

Because of the rich and the complex vascular system pituitary adenomas have a greater propensity to bleed in contrast to other brain tumours. The pituitary gland is located in a bony cavity called the sella turcica covered by the diaphragma sellae superiorly. It lies in close proximity with hypothalamus, optic chiasma and the cavernous sinus. 

Possible reasons for a hemmorhage could be:

• Rapid tumor growth that outstrips the arterial supply
• Constriction of the thin vascular network and finally ischemia, necrosis and haemorrhage
• Aggressive and invasive tumoral behaviour and hemorrhage 

Clinical Presentation

• Headache (present in 95% of the cases)
• Nausea and Vomiting
• Diplopia
• Changes in visual fields
• Ptosis

                            

Risk Factors

• Hypertension
• Head Trauma
• Major Surgery (CABG)
• Coagulopathy
• Dynamic testing of pituitary gland

How is pituitary apoplexy different from Sheehan Syndrome?

Sheehan syndrome refers to pituitary apoplexy of a nontumorous gland, presumably due to postpartum arterial spasm of arterioles supplying the anterior pituitary and its stalk. Normally, the pituitary gland hypertrophies in pregnancy and this hypertrophy, combined with locally released factors, mediates vascular spasm and renders the pituitary more susceptible to infarction from compromised blood flow. It typically presents years later or as inability to lactate after delivery due to prolactin deficiency and amenorrhea due to gonadotrophin deficiency. Also, after delivery, pubic hair fail to grow, and waxy skin depigmentation develops. Signs of hypothyroidism and hypoadrenalism may develop.

Differential Diagnosis 

• Subarachnoid haemorrhage
• Meningitis
• Hypertensive encephalopathy
• Brain abscess 
• Cavernous sinus thrombosis
• Intracerebral hematomas
• Ophthalmoplegic migraine

Diagnosis and Management

MRI is the investigation of choice in a patient with suspected pituitary apoplexy. However, if a MRI scan is not possible, a dedicated pituitary CT is another alternative. 

Medical treatment consists of the following:

• IV Fluids and administer high-dose corticosteroids. Corticotropic deficiency is present in most patients with pituitary apoplexy and it may be life-threatening. Hydrocortisone can be administered as 100–200 mg intravenous bolus followed either by continuous intravenous infusion of 2-4 mg/hour. 
• Immediately evaluate electrolytes, glucose, and pituitary hormones (random serum cortisol, TSH, free T4, prolactin, IGF-1, LH, FSH)
• Administer appropriate endocrinologic replacement therapy alone or combined with transsphenoidal surgical decompression.
  
  
  
  
  Clinically, the most important endocrine dysfunction is adrenocorticotroph hormone (ACTH) deficiency. Resolution of hypersecretory states have been reported following apoplexy, also described as ‘auto-hypophysectomy’. 
  

  
  

Management is controversial in terms of surgical intervention as some experts advocate early surgical decompression in all patients, whereas others adopt a more conservative approach for selected patients (without visual acuity or field defects and with normal consciousness). Outcome is similar with either conservative management or surgery in more recent studies. Long term with follow-up with hormonal evaluation is required to replace the deficient hormones.

Take Home:

• Pituitary Apoplexy is a life threatening cause of acute onset headache
• Maintain a high index of suspicion in any patient with acute headache and a negative conventional CT scan
• Steroid replacement and maintaining the hemodynamic stability for the cornerstone of management

References:

1. Ranabir, Salam, and Manash P. Baruah. “Pituitary Apoplexy.” Indian Journal of Endocrinology and Metabolism 15.Suppl3 (2011): S188–S196. PMC. Web. 17 Apr. 2016.
2. Rajasekaran, S., Vanderpump, M., Baldeweg, S. et al. (2011) UK guidelines for the management of pituitary apoplexy. Clinical Endocrinology, 74, 9-20. 
3. Solomon, Adriana Elena, et al. "Pituitary apoplexy: clinical features, management and outcome. Clinical study and review of the literature." Romanian Neurosurgery 22.1 (2015): 69-77.

Human and Psychological Factors in Airway Management - Dr. George Kovacs

There is a lot more to airway apart from getting the tube in. This is one of the best Airway lectures that I have ever come across. A must listen.

My take-home points:

• Asking for help is not a sign of weakness.
• Goal is not just intubation but intubation without causing any damage.
• Traditional direct laryngoscopy is not going anywhere.

For more on Airway, Check out

Airway Pearls from the CRASH Airway Course - Part 1 and Part 2

This video is also available on youtube 

New: Vaccination against Dengue!

The World Health Organization (WHO) has updated its fact sheet on Dengue and severe dengue.

Key Messages:

Introduction:

Dengue is a mosquito-borne viral disease that is transmitted by female mosquitoes mainly of the species Aedes aegypti and, to a lesser extent, Ae. albopictus. This mosquito also transmits chikungunya, yellow fever and Zika infection.

Severe dengue (also known as Dengue Haemorrhagic Fever) affects most Asian and Latin American countries and has become a leading cause of hospitalization and death among children in these regions.

Vector habits:

The Aedes aegypti mosquito lives in urban habitats and breeds mostly in man-made containers. Unlike other mosquitoes Ae. aegypti is a day-time feeder; its peak biting periods are early in the morning and in the evening before dusk. Female Ae. aegyptibites multiple people during each feeding period.

Immune response:

There are 4 distinct, but closely related, serotypes of the virus that cause dengue (DEN-1, DEN-2, DEN-3 and DEN-4). Recovery from infection by one serotype provides lifelong immunity against that particular serotype. However, cross-immunity to the other serotypes after recovery is only partial and temporary. Subsequent infections by other serotypes increase the risk of developing severe dengue.

Global Disease Burden:

The full global burden of the disease is uncertain- one estimate indicates 390 million dengue infections per year, of which 96 million manifest clinically (with any severity of disease); Another study estimates that 3.9 billion people, in 128 countries, are at risk of infection with dengue viruses.

An estimated 500 000 people with severe dengue require hospitalization each year, a large proportion of whom are children. About 2.5% of those affected die.

Clinical features:

Dengue should be suspected when a high fever (40°C/104°F) is accompanied by 2 of the following symptoms: 

• severe headache 
• pain behind the eyes 
• muscle and joint pains 
• nausea 
• vomiting 
• swollen glands or 
• rash. 

Symptoms usually last for 2–7 days, after an incubation period of 4–10 days after the bite from an infected mosquito.

Severe dengue is a potentially deadly complication due to plasma leaking, fluid accumulation, respiratory distress, severe bleeding, or organ impairment. 

Warning signs of severe dengue occur 3–7 days after the first symptoms in conjunction with a decrease in temperature (below 38°C/100°F) and include:

• severe abdominal pain
• persistent vomiting
• rapid breathing
• bleeding gums
• fatigue
• restlessness and
• blood in vomit.

The next 24–48 hours of the critical stage can be lethal; proper medical care is needed to avoid complications and risk of death.

Treatment:

There is no specific treatment for dengue fever.

Vaccination:

In late (December) 2015 and early 2016, the first dengue vaccine, Dengvaxia (CYD-TDV) by Sanofi Pasteur, was registered in several countries for use in individuals 9-45 years of age living in endemic areas.

The Strategic Advisory Group of Experts (SAGE) on immunization will review the dengue vaccine and recommendations are expected in April 2016.

Prevention and Control:

At present, the only method to control or prevent the transmission of dengue virus is to combat vector mosquitoes through:

• preventing mosquitoes from accessing egg-laying habitats by environmental management and modification;
• disposing of solid waste properly and removing artificial man-made habitats;
• covering, emptying and cleaning of domestic water storage containers on a weekly basis;
• applying appropriate insecticides to water storage outdoor containers;
• using of personal household protection such as window screens, long-sleeved clothes, insecticide treated materials, coils and vaporizers;
• improving community participation and mobilization for sustained vector control;
• applying insecticides as space spraying during outbreaks as one of the emergency vector-control measures

Useful Links:

Link to the updated fact sheet:

http://who.int/mediacentre/factsheets/fs117/en/

Link to WHO’s ‘Dengue: guidelines for diagnosis, treatment, prevention and control — New edition’ (published in 2009):

http://apps.who.int/iris/bitstream/10665/44188/1/9789241547871_eng.pdf

Link to WHO’s Global Strategy for Dengue Prevention and Control 2012-2020 (published in 2012):

http://apps.who.int/iris/bitstream/10665/75303/1/9789241504034_eng.pdf?ua=1

Link to WHO’s page on Dengue Vaccine Research:

http://who.int/immunization/research/development/dengue_vaccines/en/


Author:

Dr. Liaquat Roopesh MBBS, MD (Community Medicine) 

Alumnus of Christian Medical College, Vellore. 

Interests: teaching and medical education

Originally published at communitymedicineforasses on March 22, 2016. Reposted with permission.