breathing issues

December 6 2022

Extubation Failure

PME-Admin article, medical breathing issues, children, extubation, infants, pediatric, pediatrics, ventilator

Extubation Failure
Santa J. Bartholomew MD

Mechanical ventilation is often required for critically ill patients in the ICU. As the acute phase of illness resolves, the goal is to wean the ventilator, allowing the patient to breathe more on their own (spontaneous breathing trials), and to successfully extubate, or remove the artificial airway. Patients may tolerate weaning the ventilator, but fail extubation. Extubation failure is defined as the inability to sustain spontaneous breathing after the removal of the artificial airway (an endotracheal tube or tracheostomy tube) and require reintubation within a specified time period, usually defined as 24-72 hours or up to 7 days.

Causes of Extubation Failure

Excessive secretions affecting airway patency
Respiratory Failure: Most common cause. Manifest as increased work of breathing, hypoxia (insufficient oxygen), hypercapnea (excessive carbon dioxide in the blood), use of accessory muscles for breathing, respiratory acidosis
Upper airway edema affecting patency of airway
Neurological impairment: May be secondary to primary illness, encephalopathy, or residual effects of sedation
Neuromuscular Diseases (Guillain-Barre syndrome, Duchenne Muscular Dystrophy)
Acute heart failure
Poor nutrition
Other risk factors: Severity of illness on admission to ICU, prolonged intubation, continuous sedation

Photo + caption source: Fliesler, N. (2020, May 11). Children with COVID-19 in the PICU: A snapshot. Boston Children’s Answers. https://answers.childrenshospital.org/covid-19-picu

It is essential for the Health Care Provider to identify patients at a higher risk for extubation failure/need for re-intubation, as extubation failure can have detrimental consequences. It is also imperative that all appropriate equipment and personnel are on hand for difficult extubation.

Consequences of Extubation Failure

The incidence of extubation failure has been noted to be between 6% and 47%. Nosocomial pneumonia is significantly increased in patients failing extubation (47% versus 10%). Additional consequences of extubation failure are:

Prolonged ICU stay and hospitalization
Prolonged mechanical ventilation
Need for tracheostomy
Increased medical cost
Increased morbidity and mortality

Mortality is increased with increasing duration of time between extubation and reintubation. This is due to deterioration in the patients’ condition leading to organ dysfunction and failure.

Predictors of Extubation Failure

There are many risk factors for extubation failure. It is vital for the Healthcare Provider to do a thorough assessment of extubation readiness. Parameters that are used to predict failure of extubation are often categorized into parameters assessing respiratory mechanics, airway patency and protection of airway, and cardiovascular reserve. Successful extubation is dependent on adequate cough strength, minimal secretions, and mental alertness or the neurological ability to maintain adequate spontaneous breathing.

Successful spontaneous breathing trials: These trials allow the patient to breath more on their own while the artificial airway remains in place. This allows the Healthcare provider to better assess respiratory muscle reserve/weakness and work of breathing
Adequate cough strength: Important for patient to be able to clear airway of secretions. This may be affected due to weak respiratory muscles and laryngeal dysfunction
Secretions: Excessive secretions or the patient’s inability to handle their secretions
Neurological Dysfunction: Study results vary on the impact of neurological impairment on extubation failure. Most recently, a GCS ≥10 is prerequisite for successful extubation
Cuff leak: Laryngeal edema and airway obstruction following extubation may lead to extubation failure. When the cuff on the artificial airway is deflated, the amount of leak noted depends on the degree of laryngeal and airway edema. Glucocorticoids (steroids) are often administered prior to extubation to reduce airway edema
Vital Signs and Blood Gases: Spontaneous breathing requires the heart to work harder. Patients with poor heart function or following cardiac surgery may be at an increased risk for failing extubation. An increase in heart rate and respiratory rate during spontaneous breathing trials may be an indicator of extubation failure. Other findings may include an increase in lactic acid, an increase in PaCO2 (carbon dioxide) in the blood, a decrease in the blood pH (indicating acidosis), or decreased oxygen content in the blood.

Predictors of extubation failure may not apply to neurologically injured patients as the ability to protect their airway and clear secretions may be impaired independently of their ability to ventilate.

*Photo + caption source: Mark, N. (n.d.). WEANING FROM THE VENTILATOR. Retrieved November 30, 2022, from https://static1.squarespace.com/static/5e6d5df1ff954d5b7b139463/t/5e7a8442e1294b32cd7106b1/1585087555516/ICU_one_pagers_vent_weaning.pdf

Photo + caption source: Kurachek, S. (2003). Extubation failure in pediatric intensive care: A multiple-center study of risk factors and outcomes. Critical Care Medicine, 31(11). https://doi.org/10.1097/01.CCM.0000094228.90557.85

Management of Failed Extubation

Extubation failure is a common occurrence in the ICU. Even with successful spontaneous breathing trials, patients remain at risk for extubation failure following removal of the artificial airway due to other factors and circumstances.

Nasal Intermittent Mandatory Ventilation (NIMV)/Intermittent Mandatory Ventilation (IMV): Use of NIMV/IMV has been shown to provide the additional respiratory support needed to avert/prevent reintubation in some patients.
High-Flow Nasal Cannula: Treatment for hypoxemic acute respiratory failure. Delivers a high flow/fraction of inspired oxygen (FiO2) and generates a low level of positive pressure. This provides support for patients with weak respiratory muscles and improves the work of breathing and respiratory rate.
Oxygen alone should not be used to correct hypoxemia that is caused by hypoventilation (ineffective breathing and ventilation). In doing so, the respiratory drive can be suppressed and precipitate acute respiratory failure
Steroids: Edema of the upper airway is difficult to assess before extubation. Upper airway edema is a risk factor for reintubation. Evaluating for a cuff leak prior to extubation predicts stridor but not the need for reintubation. In a double blinded trial, four (20 mg) doses of prophylactic use of methylprednisolone initiated 12 hours before extubation at 4 hour intervals versus placebo, resulted in reduction (22% to 3%) of laryngeal edema and reduction in reintubation (8% to 54%) due to laryngeal edema.

Evidence is suggestive that prophylactic administration of glucocorticoids and early institution of non-invasive ventilation may prevent reintubation in some patients. If necessary, early reintubation and reinstitution of ventilation should be instituted.

Photo + caption source: Frat, J.-P. (2017). High-Flow nasal oxygen therapy and noninvasive ventilation in the management of acute hypoxemic respiratory failure. Annals of Translational Medicine, 5(14).

RESOURCES

Agarwal, A. (2017). Respiratory Care of Patients with Neuromuscular Diseases.
Coplin, W. (2000). Implications of Extubation Delay in Brain-Injured Patients Meeting Standard Weaning Criteria. American Journal of Respiratory Critical Care Medicine, 161, 1530–1536
Frat, J.-P. (2017). High-Flow nasal oxygen therapy and noninvasive ventilation in the management of acute hypoxemic respiratory failure. Annals of Translational Medicine, 5(14).
Kulkarni, A. (2008). Extubation failure in intensive care unit: predictors and management. Indian Journal of Critical Care Medicine, 12(1), 1–9. https://doi.org/10.4103/0972-5229.40942
Kurachek, S. (2003). Extubation failure in pediatric intensive care: A multiple-center study of risk factors and outcomes. Critical Care Medicine, 31(11). https://doi.org/10.1097/01.CCM.0000094228.90557.85

Disclaimer: This web site provides general information about pediatric health and related subjects. The information and other content provided on this website or in any linked materials are not intended and should not be considered, or used as a substitute for, medical advice, diagnosis or treatment. Never disregard professional medical advice or delay in seeking it because of something that you have read on this website or in any linked materials.

A child with Pneumonia in an incubator and breathing dome

September 27 2022

Periodic Breathing in Infants

PME-Admin article, medical apnea, breathing, breathing issues, children, pediatric, pediatrics, periodic breathing

Periodic Breathing in Infants – Santa J. Bartholomew M.D.

What is Periodic Breathing in Infants?

Periodic breathing is a normal condition that affects healthy moderately preterm infants. It is characterized by periods of irregular breathing in which the infant breathes rapidly for several cycles then has a 5 to 10 second pause in breathing, only to repeat the cycle again.

Periodic breathing usually occurs during sleep and is often seen in premature babies, although it can happen in term infants it is quite rare.

How is periodic breathing different from apnea?

Apnea is a developmental disorder that reflects physiologic immaturity on the part of an infant in which breathing stops for more than 20 seconds. Apnea can be caused by many things, including respiratory infections, heart problems, reflux and most commonly prematurity. Unlike periodic breathing, apnea can be life-threatening and requires immediate medical attention.

In this blog post, we’ll discuss how to diagnose periodic breathing in infants, as well as what you should do if your child exhibits symptoms.

Unlike periodic breathing, apnea can be life-threatening and requires immediate medical attention.

Signs and Symptoms of Periodic Breathing in Infants

The most common symptom of periodic breathing is periods of irregular breathing during sleep. Other signs and symptoms include:

Crying or grunting during periods of irregular breathing
Stopping breathing for 5-10 seconds followed by deep sighing or gasping and repeat of the breathing pattern.

Signs and Symptoms of Apnea in Infants

Apnea can become evident in preterm infants in the first two or three days of life who are breathing unassisted from support.

There are periods of 15+ seconds or more of not breathing.
There may be color change: bluish lips
The heart rate in the infant may slow down

Treatment for Periodic Breathing in Infants

Most healthy babies outgrow periodic breathing on their own within a few months. As such, treatment is typically not necessary. Simply following guidance for safe sleeping, such as lying your infant on his/her back, can often alleviate symptoms.

When should you seek medical attention?

Parents should call 911 if a child exhibits more serious symptoms and is in need of emergency help. Examples of times when it may be necessary to contact 911 include:

Child stops breathing, their skin turns blue, or they become unconscious
Child experiences severe trouble breathing with chest sinking in, using their belly muscles to breathe, or their nostrils begin flaring during an episode of difficult breathing.
In severe cases, it may be necessary for you to proactively administer rescue breathing and follow any instructions provided by emergency providers while you wait for assistance to arrive.

Final thoughts on periodic breathing in infants

If you think your infant may be experiencing periodic breathing, it’s important to talk to your healthcare provider. They will be able to properly diagnose the condition and recommend treatment options that are best for your child. Most healthy babies outgrow periodic breathing on their own, but there are some actions parents and providers can take that can help alleviate the symptoms in the meantime. With proper care, infants will be back to regular breathing in no time.

Resources

Sleep apnea: https://www.ncbi.nlm.nih.gov/books/NBK441969/
Periodic breathing timing: https://www.stanfordchildrens.org/en/topic/default?id=breathing-problems-90-P02666
Treatment: https://myhealth.alberta.ca/Health/aftercareinformation/pages/conditions.aspx

Pediatric Medical Experts Acute Stridor Children

April 19 2022

Acute Stridor in Children

PME-Admin article, medical acute stridor, airway obstruction, breathing issues, children, pediatric, pediatrics

Acute Stridor in Children — Santa J. Bartholomew M.D.

Acute Stridor is a harsh, grating respiratory noise that can often be heard without a stethoscope and is caused by airflow obstruction through the upper airway. The noise is caused by rapid and turbulent flow through a narrowed airway. The most common causes of stridor in infants without fever include congenital malformation of the airway or compression of the airway by other great structures around the airway, subglottic stenosis, laryngomalacia, tracheomalacia. In older children viral or bacterial infection in the airway, foreign bodies or other anatomic issues such as laryngeal cleft or bronchogenic cyst can cause this noise. The cause of this noise varies by age but the predominant clinical symptom is the same. We will be discussing acute stridor in children in this article, stridor in infants will follow in the series.

Listen: audio of Acute Stridor in children

The noise is caused by rapid and turbulent flow through a narrowed airway.

Causes of Acute Stridor Based on Anatomy

ACUTE STRIDOR

Acute Stridor, the topic of this article, is often of quick and dramatic onset making anatomic issues less likely and infectious causes and foreign bodies more common.

Laryngotracheitis

LARYNGOTRACHEITIS / VIRAL CROUP

Laryngotracheitis or Viral Croup develops over hours to days in children with previous upper airway infection. It typically affects children 6 months to three years old. Runny nose, fever and stridor are all usually present. It is a self-limited disease that ususaly resolves in 3 to 5 days.

Bacterial tracheitis

BACTERIAL TRACHEITIS

Bacterial tracheitis is generally, happens in the first 6 years of life. Most children have a URI prodrome but then present with severe respiratory distress, anxiety secondary to shortness of breath and fever. They may also have drooling, muffled voice and their position of comfort is upright. Much like classic H. flu epiglottitis of the past prior to vaccine availability. It is treated with controlled airway management and IV antibiotics in the Pediatric Intensive Care Unit. The airway is assessed intermittently by ENT to assess readiness for extubation.

Epiglottitis

EPIGLOTTITIS

Epiglottitis is an inflammation or infection of the epiglottis which is the structure that protects the trachea during swallowing. Inflammation of this structure can cause acute airway obstruction and be deadly. Children present with anxiety, severe respiratory distress, drooling and muffled speech. Classically this has been caused by H. Influenza however since the development of a vaccine incidence of epiglottitis has dropped dramatically. It can be caused by virus as well but this is much less common. Treatment of viral epiglottitis is airway management and supportive care. In the case of classic epiglottitis IV antibiotics are added to the care plan.

Retropharyngeal abscess

RETROPHARYNGEAL ABCESS

Retropharyngeal abscess occur between ages 2 years to 5 years old. May be indistinguishable from peritonsillar abscess or uncomplicated pharyngitis but as the disease progresses fever and drooling become more evident and inspiratory stridor. CT with IV contrast will help make the diagnosis. Treatment is IV antibiotics and surgical drainage.

Peritonsillar abscess

PERITONSILLAR ABCESS

Peritonsillar abscess arising as a complication of pharyngitis or tonsillitis, usually peaks in children about 10 years old when streptococcal pharyngitis peaks. Typically presents with severe sore throat (usually one side worse than other), fever, muffled voice, drooling, neck swelling. Treatment is IV antibiotics and surgical drainage.

Foreign Body Aspiration

FOREIGN BODY ASPIRATION

Foreign body aspiration should always be suspected in infant or toddler with acute airway compromise but this often does not present with fever. Incidence peaks about 3 years old Witnessed choking helps make the diagnosis but this is often not the case and not all FB are radio-opaque (able to be seen on x-ray) so high index of suspicion is necessary.

Anaphylaxis

ANAPHYLAXIS

Anaphylaxis is commonly caused by food or medications. It is a severe and life-threatening swelling of the airway that involves the retropharynx (back of the throat) and the larynx (the voice box). It commonly has severe acute respiratory symptoms after ingesting the offending trigger substance but the child may also have hives, itching and mouth swelling as well as diarrhea, vomiting and abdominal pain. Treatment includes IM epinephrine immediately to slow airway swelling, glucocorticoids, H1 /H2 antihistamines help with itch but do not relieve airway swelling, sometimes bronchodilators may be used as well. Airway protection may be necessary.

October 31 2021

RSV and HMPV in Infants and Children

PME-Admin article, medical breathing issues, children, hmpv, infants, pediatrics, rsv

RSV and HMPV in Infants and Children — Santa J. Bartholomew M.D.

Winter is the time for viral season in infants and children. Many of the winter viruses are spread by droplet and secretions making them very transmissible from toddlers to infants and each other as well as their adult caretakers. Since toddlers are at a developmental age of still sharing toys, drinks and germs – diseases such as respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are very common in hospitals and outpatient offices in the fall through early spring.

These viruses have no primary treatment like a bacterial pneumonia or infection might but can cause severe lung disease none-the-less and make children vulnerable for bacterial disease as the lining of the lung is injured by the inflammatory response that these viruses incite in the body. Many older children and toddlers display these diseases as just a “very bad cold”: fever, runny nose, coughing and sneezing, poor appetite. Slowly in 7-10 days these symptoms abate, and the child begins to feel better and slowly returns to normal the beginning of week two.

ASSESSING RISK

Pediatricians are tasked during the winter months when assessing these children in assessing risk. The natural history of both viruses is the same. Those infected HMPV tend to be slightly more at risk of being super-infected with bacterial disease like Staphylococcus Aureus or Streptococcus pneumoniae pneumonia’s than those primarily infected with RSV but the natural course of disease is essentially the same. So, what makes these diseases deadly?

Newborns and preterm newborns are obligate nose-breathers so if they become congested with mucous and secretions, they can become very distressed.

RISK FACTORS

If the disease infected healthy people age 5 to 30 years old and that was all, everyone would get a cold and then get better in 7-10 days. But 5 years olds live with older siblings who may have asthma or cancer or an immune disease, their families may have a newborn infant, or a preterm infant recently discharged from the NICU. These children have different risk assessments than the initial toddler: the healthy five-year-old. Pediatricians, ED physicians who see children, pediatric hospitalists in caring for patients with RSV and HMPV are not expected to cure a viral disease without as yet a known cure but to assess risk based on the host (or child) that is infected.

Newborns and preterm newborns are obligate nose-breathers so if they become congested with mucous and secretions, they can become very distressed, sometimes turn blue or have great difficulty breathing and eating. They can sometimes have periods of apnea as a response to their disease. These children are often admitted to the hospital for care, they are placed on monitors looking for apnea or for periods of low oxygen levels that may need to be supplemented so as not to injure their developing brain. Because their noses are blocked with secretions they often will not feed and are greater risk for dehydration and the things that may follow this such as hypovolemic shock and kidney failure. The physician in this circumstance is not called upon to cure these children’s virus but to anticipate the child’s response based on age and health and then determine where and how they are best cared for based on available literature and experience.

As newborns are more likely to be admitted to the hospital with RSV and HMPV children 5-10 years old are more likely to be sent home with instructions for supportive care. However, a 5-year-old asthmatic who has a history of being on a mechanical ventilator in the past who now presents, with HMPV who has breathing difficulty to the ED, is at risk of developing a severe asthma attack as the inflammation from the virus progresses. This 5-year-old may be best treated for the peak of his or her disease in the hospital.

A child undergoing chemotherapy who has very few white cells would be a child best cared for by seeing their doctor daily or being in the hospitalized until it is clear they will not be super-infected with a bacterial which could easily lead to their death.

So, winters are difficulty times of doctors who care for infants and children. Viruses and risk abound and they must make savvy, wise decisions often with limited information and quickly as offices and ED’s become overwhelmed with sick infants and children. But good risk assessment is a must!! Careful questioning about other breathing diseases, heart disease, immune diseases, previous hospitalizations, other illnesses. These few extra minutes to gather in the information to make a good risk assessment may save a child’s life.

October 8 2021

Asthma in Children

PME-Admin article, medical asthma, breathing issues, children, pediatrics

Asthma in Children — Santa J. Bartholomew M.D.

As we head into fall with leaves falling and more rain, mold counts rise and there is a spike in winter viral infections. During this time, children with asthma come to emergency departments and get admitted to hospitals in droves.

Asthma defined by episodic and reversible airway constriction and inflammation is triggered by many allergens. Among the top allergens are mold and viral inflammation, making fall and winter challenging for families of children with asthma. Because asthma is so common, affecting 1 in 12 American children and costing $80 billion/annum in medical care, not to mention missed school and missed work for parents, it has long been a disease that garners great interest in the prevention of episodes.

Drugs that provide relief during wheezing attacks still do not provide 100% of prevention from asthma attacks causing hospitalization. Further, asthma disproportionately affects minorities and socioeconomically disadvantaged children. Black children have the highest morbidity and mortality rates in the country and are 9 times more likely to die from their asthma than their white counterparts.

PATHOPHYSIOLOGY OF ASTHMA

Asthma exacerbations are the leading cause of ED visits and account for one of the top 3 reasons for admissions of children. The pathophysiology of asthma is a highly complex, immune-mediated inflammatory disease that causes intermittent and reversible lower airway obstruction which includes constriction of the smooth muscle of the airway and narrowing in the airway because of this constriction as well as mucous production caused by the triggering agent.

Asthma is so common, affecting 1 in 12 American children and costing $80 billion/annum in medical care…

The combination of these issues causes an obstructive pattern of breathing in which a child can inhale but cannot exhale the breath easily and over time this causes the lungs to over-inflate. This overinflation causes a feeling of shortness of breath and can actually impact blood flow in and out of the heart in severe attacks. The current understanding of asthma immunology suggests that the type and severity of asthma a child has may be related to exposures they have very early in life.

Common triggers

- Viruses: particularly rhinovirus and Influenza A are associated with the largest spike in asthma attacks in the fall. Influenza A associated pediatric deaths between 2000-2016 found that 12% of these children suffered from severe asthma exacerbations
- Irritants: cigarette smoke (many parents will attest to smoking outside the home but smoke imbedded in clothing is as powerful a trigger as direct exposure), candles, incense, vapor from electronic cigarettes, wood fire particulates, air pollution
- Allergens: mold spores, cockroaches and cockroach detritus, rat dander, mice dander, dust mites and pet dander
- Weather: rapid changes in temperature and/or barometric pressure
- Medications: B-blockers, aspirin, NSAID
- Exercise induced: rare and more commonly found in poorly controlled asthmatics
- Poor mental health of care provider: usually associated with poor control of child’s asthma

ENVIRONMENTAL TRIGGERS

Environmental triggers are a major contributor to health disparities in pediatric asthma and a thorough review of these can reduce a child risk of having a life-threatening asthma attack as much as 40%, for example just removing triggers from the environment such as pets and carpet that can catch dander and mites.

Recommendations for trigger removal

1. Dust mites—provide mattress and pillow encasements, vacuum twice a week, consider removal of carpet in the bedroom if there are significant nighttime symptoms, remove any stuffed animals from the child’s bed or recommend machine washing of stuffed animals in hot water
2. Mold spores—avoid humidifier use; remediate and water damage/mold in the home
3. Pests—keep food out of the bedroom and in closed trash containers, exterminate if needed (preference of traps over sprays)
4. Animal dander—consider removal of animal if that is an option or recommend special hypoallergenic breeds

DIAGNOSIS

Diagnosis remains largely clinical as most children under 5 years old cannot perform the pulmonary functions tests (PFT’s) required for diagnosis. A child with a family history of asthma who has episodic and recurring chest tightness, cough and difficulty breathing +/-wheezing in response to common triggers most likely has asthma. These children may also have allergic rhinitis, eczema. There is now an Asthma Predictive Index to help outpatient providers objectively review symptoms to assist in diagnosis.

Asthma Predictive Index

MAJOR CRITERIA	MINOR CRITERIA
Parental physician-diagnosed asthma	Wheezing unrelated to colds
Physician-diagnosed atopic dermatitis	Eosinophils 4% in circulation
Allergic sensitization to at least one aeroallergen	Allergic sensitization to milk, eggs, or peanuts

mAPI criteria for use in patients ≤ 3 years old with ≥ 4 wheezing episodes per year. At least one or 2 major criteria are required.

Of course, as a health care provider one must consider the other possibilities for wheezing which are many and age dependent including GERD, BPD, chronic aspiration, trachea and bronchomalacia, bronchiectasis, food allergy, panic attack, vocal cord dysfunction, foreign body aspiration, mass in airway or airway anomaly, cystic fibrosis. Once these are ruled out and the diagnosis of asthma is made then one can decide on a treatment path.

TREATMENT

The overall goal in treatment id to reduce impairment and maintain a good quality of life for the child allowing for exercise and play and keeping the child out of the hospital and off long-term systemic steroids of possible. Treatment is generally multi-pronged.

Short term and acute treatment
- B-agonists like albuterol are the mainstay of treatment in exacerbations for quick relief of bronchospasm but may cause fast heart rate and shakiness.
Anticholinergics
- Ipratropium bromide: takes longer to work than Albuterol but lasts longer so can be used in the ED together with Albuterol for short and longer term relief
Steroids: short course
- Decadron, prednisone or prednisolone in short courses can be used to abate inflammation in the airway but used too often can cause adrenal suppression leading to catastrophic consequences.
Controller medications to avoid exacerbations
- Leukotriene inhibitiors:
- Immunomodulators
- Inhaled steroids
- Long-term anticholinergics
Inpatient adjunct medications
- Albuterol delivered in high doses via a continuous delivery system
- Large doses of IV steroid to quickly abate inflammatory response
- Magnesium sulfate
- IM epinephrine
- IV Terbutaline: IV B-agonist
- Helium
- General anesthesia

CONCLUSION

Asthma is a common problem in children and can be controlled with good control of environment and controller medications and aggressive attention to exacerbations. Most pediatricians are well educated in how to manipulate these medications for the best outcome, but this also relies on compliance of the family. Asthma is so common that people become complacent and stop taking their medications or expose themselves to risks like smoking which can lead to catastrophic consequences. Thousands of children die annually, unnecessarily, because of these actions.

In hospitals children die because they have been brought to medical attention too late, their bronchospasm cannot be broken quickly enough despite heroic activities. The best way to avoid these deaths is compulsive compliance to a medication and life plan.