• NMD stands for Neuromuscular Disorder

Spinal Muscular Atrophy (SMA)

• Type 1 SMA, also known as "Werdnig Hoffmann," occurs in infants.
• Muscles are structurally fine, but nerves to muscles are non-functional.
• SMA is related to the survival motor neuron 1 (SMN1) gene.
• A defective SMN1 gene doesn't produce enough SMN protein to allow motor neurons to survive.
• As motor neurons are lost, muscles no longer receive signals from the brain, leading to weakness and atrophy.
• SMA is a recessive genetic disease with symptoms potentially starting in utero.
• It is usually diagnosed by 6 months.
• SMA is very progressive and can lead to death by age 3 without treatment.

Symptoms of SMA

• "Floppy baby" with poor muscle tone.
• No motor function, but still has sensory function.
• Patients can't move but can feel.
• Patients tend to lay like frogs, with knees and arms bent.

Spinraza (nusinersen)

• Increases SMN protein production
• Must be injected into the cerebrospinal fluid (CSF).
• Three loading doses are administered, separated by 2 weeks each.
• A fourth dose is given 30 days later, and repeat doses are given every 4 months.
• $750,000 for the first year of treatment and $375,000 per year afterward.

Zolgensma (onasemnogene abeparvovec-xioi)

• A gene therapy replacing the non-working or missing SMN1 gene with a new working copy.
• Approved for children under 2 years old.
• Given via IV infusion over 1 hour; only one dose is needed for life.
• The cost of Zolgensma is $2.125 million for one dose.

Muscular Dystrophy

• Is a genetic disease with many types, where the muscles are not functional, but nerves are fine.

Duchenne's Muscular Dystrophy

• Sex-linked and recessive, occurs only in males, and doesn't present in infancy.

Symptoms of Duchenne's Muscular Dystrophy

• All related to loss of calf and hip muscle function.
• Muscles look big and bulky due to fibers being replaced by fat.
• Begins with difficulty walking up steps, walking on toes, waddling, and difficulty getting up from a seated position.
• Usually diagnosed by age 5 or 6, patients will need a wheelchair by age 10-15.
• Patients live longer with a trach and vent, and without these, they die by age 20.

Extracorporeal Membrane Oxygenation or Extracorporeal life support

• Occurs outside the body
• A modified cardiopulmonary bypass version but for an extended time.
• It can be done emergently ("crash on to ECMO") or as a planned procedure.
• Supports the heart and lungs (VA) or just the lungs (VV).
• ECMO is a supportive therapy to allow the body to rest.

How ECMO Works

• Cannulas in the patient's vessels drain blood from the body to the ECMO pump.
• The pump circulates the blood through an oxygenator membrane for gas exchange.
• The blood returns to the patient via cannulas in the patient's vessels.

ECMO FLOW: Centrifugal Pump

• A magnetic pump "spins" at an RPM to create pump flow (L/min).
• VA ECMO flow provides cardiac output.
• VV ECMO flow only controls blood to the oxygenator.
• Pre-pump pressure is negative, and post-pump pressure is positive.
• Centrifugal ECMO pumps depend on pre-load and after-load.
• It requires a healthy circulating volume for the pump to work.
• "Chugging" indicates no fluid is moving through.
• High native blood pressure may impede ECMO pump function.
• Consider sedation, vasodilators vs. pressors to help accommodate the ECMO pump

ECMO Sweep

• The oxygenator membrane acts as a lung by removing CO2 and supplying O2 to venous blood.
• It replaces the need for native lung function in both VV and VA ECMO.
• Patients doesn't require support from the vent.

The Sweep Gas

• Air and oxygen are supplied via a blender.
• Sweep gas Fi02 supplies O2 to blood.
• Sweep gas flow removes CO2 from the blood.

VA (Veno-Arterial) ECMO

• Used for full cardiopulmonary support.
• Venous cannulas are large and drain un-oxygenated blood from the body to the pump; more than one cannula may be used for large patients to increase flow.
• VA ECMO can be accessed percutaneously via the RIJV or FA, or directly into the right atrium.
• Arterial cannulas are smaller and return oxygenated blood from the pump to the body.
• VA ECMO can be accessed percutaneously via the RCA or IVC or directly into the aorta.

VA ECMO Characteristics

• VA ECMO bypasses the heart.
• It provides the patient's entire cardiac output and lung support.
• Increase of flow will improve cardiac output and blood pressure.
• If cardiac arrest occurs, compressions may not be effective, but an increase in pump flow may be.
• Sweep gas influences lung function.

VV (Veno-Venous) ECMO

• VV ECMO is used for full pulmonary support and not cardiac support.
• It utilizes one dual-lumen cannula, typically in the RIJV to IVC.
• Blood is sucked in from one lumen via the IVC and SVC and returned via the arterial lumen in the right atrium.
• Monitor for recirculation.
• Oxygenated blood can be inadvertently pulled back into the venous circulation without entering the right atrium.
• The mixed venous saturation (SvO2) should be between 65-75%; values above this indicate recirculation.
• Decrease of flow mitigates recirculation.

VV ECMO Characteristics

• The patient supplies native cardiac output; increasing flow will not increase cardiac output or blood pressure.
• Blood pressure will be pulsatile due to cardiac function.
• If cardiac arrest does occur, compressions may be needed.
• Patients generally have lower SpO2 on VV than VA ECMO.

Inclusion Criteria for ECMO

• 34 weeks gestation and birth weight >2000g.

• No intracranial hemorrhage (>Grade 1).
• Controllable bleeding.
• Mechanical Ventilation of less than 10-14 days and reversible lung disease.
• Absence of concomitant condition that would render the use of ECMO futile or not in the best interest of the patient, such as anomalies or central nervous system dysfunction.

Exclusion Criteria for ECMO

• Lethal Congenital Anomalies
• Irreversible underlying condition.
• Condition incompatible with normal healthy childhood.
• Incurable diseases.
• Metastatic cancer and AIDS.
• Mechanical ventilation >10 days.
• 22% survival rate.
• Chronic multi-organ dysfunction or irreversible brain damage.

ECMO ventilation strategies

• Pre-ECMO settings are generally high involving conventional, HFOV, OI >40 indicates the need for ECMO.
• Effects of paralytics and barotrauma should be considered with early ECMO when possible.
• During ECMO, the vent settings are low to provide rest for the lungs and avoid barotrauma.
• Provide pulmonary toilet with rescue settings if the patient has come off of ECMO for any reason; similar to pre-ECMO settings.
• Post ECMO ventilator settings should not be the same or greater than Pre ECMO settings.
• ECMO stays on if settings are high.

ECMO Complications

• Bleeding risk
• Accidental decannulation.
• Stroke Clotting
• Malfunctioning Equipment.

Pneumonia

• Classifications based on pathogen, clinical setting, or when the pathogen cannot be identified.

General Pneumonia (PNA) Terminology

• Double pneumonia affects both lungs
• Walking pneumonia is a milder form

Location of Pneumonia

• Bronchopneumonia affects the bronchioles
• Lobar pneumonia affects a lobe of the lung
• Interstitial pneumonia affects the tissue between the alveoli

Community-Acquired Atypical Pneumonia

• Clinical presentation is often subacute.
• Patients display pulmonary and other symptoms.
• Usually caused by the Mycoplasma organism
• It causes bacterial and viral pneumonia symptoms including violent coughing with only small amounts of white mucus.
• Atypical refers to the organisms' escape of identification by standard bacteriologic tests.
• Generally only a moderate amount of expectorated sputum.
• Absence of alveolar consolidation
• Moderate elevation of white cell count.
• Lack of alveolar exudate

Etiology of Community-Acquired Atypical Pneumonia

• Coxiella burnetii: Gram-negative bacterium causing Q fever in humans.
• Chlamydia: Including C. pneumoniae, C. psittaci, and C. trachomatis.
• Viruses: Account for about 50% of all pneumonias. Several are associated with a community-acquired atypical pneumonia.

Viruses Associated with Atypical Pneumonia

• Respiratory syncytial virus
• Parainfluenza virus; Paramyxovirus group are related to mumps, rubella, and RSV.
• Influenza A and B: Most common causes of viral respiratory tract infections
• Adenovirus
• Human metapneumovirus; Second most common cause of lower respiratory infection in young children.

Hospital-Acquired Pneumonia

• Also called hospital-associated and nosocomial pneumonia.
• Pneumonia develops 48+ hours after hospital admission and that was not present upon admission.
• Most common pathogens: Pseudomonas aeruginosa, Methicillin-sensitive Staphylococcus aureus, and MRSA.

HCAP (Healthcare-Associated Pneumonia)

• Affects patients who have recently been in an acute care hospital within 90 days of infection or who reside in nursing homes or long-term care facilities.
• Affects patients who have: received parenteral antimicrobial therapy (IV antibiotics), chemotherapy, or wound care within 30 days of PNA.

Aspiration Pneumonia

• Involves toxic injury to the lung e.g. caused by gastric acid.
• Involves obstruction by foreign bodies or fluid and infection.
• Presumed to be the cause of nearly all cases of anaerobic pulmonary infections.

Fungal Diseases of the Lung-Primary Pathogens

• Coccidioidomycosis Caused by inhalation of the spores of Coccidioides immitis
• Endemic in hot, dry regions, especially California, Arizona, Nevada, New Mexico, Texas, and Utah (California fever, desert rheumatism, San Joaquin Valley Disease, and Valley fever).
• Made by direct visualization of distinctive spherules in microscopy of the patients sputum, tissue exudates, biopsies, or spinal fluid

Blastomycosis

• Also called Chicago disease, Gilchrist disease, American blastomycosis
• Occurs in people living in the South-Central and midwestern United States and Canada.
• Primary portal of entry is the lungs: Cough is frequently productive and the sputum is purulent.
• Determined via direct visualization of yeast in sputum smears or culture.
• Opportunistic pathogens
• Candida albicans, a cause of thrush
• Cryptococcus neoformans thrives in a high nitrogen content of pigeon droppings
• Aspergillus is found in soil, vegetation, leaf detritus, food, and compost heaps.
• Pneumonia in the Immunocompromised Host
• Cytomegalovirus (CMV): Member of the herpesvirus family; is the most common viral pulmonary complication of AIDS.
• Pneumocystis jirovecii (also known as Pneumocystis carinii0): An often fatal pneumonia form seen in immune suppressed patients, and the Major pulmonary infection seen in patients with AIDS and HIV infection.
• Varicella (Chickenpox): Has a mortality rate of varicella pneumonia of about 20%.
• Rubella (Measles): Is the severe Acute respiratory syndrome
• Lipoid Pneumonitis: Caused by aspiration of mineral oil
• Avian influenza A

Overview of Cardiopulmonary Manifestations in Pneumonia

• Alveolar consolidation
• Increased alveolar-capillary membrane thickness
• Atelectasis
• Excessive bronchial secretions during the resolution stage

Tests and Procedures for Pneumonia

• Abnormal sputum examination
• Chest Radiograph; Increased density from consolidation and atelectasis.
• Air bronchograms and Lung abscesses, also air and fluid filled cavities can be found.
• Pleural effusions/empyema are dependent on the causative agent and the stage of the pneumonia process.
• Refer to Chapter 14: 10-11,14-16, 18, 32, 34, 41-49, Figure:14.14, Table 14.1, Box 14.4, Table 14.2 for detailed information.

Lung Volumes and Flows

• Measurement of lung volumes and flows
• Vt has two components; The Alveolar volume (Va) and the Dead space volume (Vd).
• Alveolar volume (Va) is the portion of the Vt that effectively exchanges with alveolar capillary blood.
• Dead space volume (Vd) is the portion of Vt that does not exchange with capillary blood.
• The common reference range cited for Vd is 25% to 40% of the Vt, also known as Physiologic dead space
• the conductive airways and alveolar units that are ventilated but not perfused.

Vt (Tidal Volume)

• It measures 5 to 8 mL/kg IBW, Vt <5 ml/kg indicates a respiratory problem; Pneumonia, COPD, CHF, ARDS, CNS depression and metabolic acidosis, sepsis, and neurologic injury.
• Vt=VA+VD
• Vd=25% to 40% of the Vt
• VD >60%: Patient need ventilatory support.

Spontaneous Breathing Trial (SBT) Failure

• Vt <300 ml or <4 ml/kg
• SpO2 <85% to 90%
• Blood pressure and heart rate change >20%.
• Respiratory Rate >35 breaths per minute
• Changes in mental status
• Accessory muscle use
• Diaphoresis
• Criteria indicating failure of a SBT
• An increase or decrease of 20% in blood pressure or heart rate
• An Oxygen saturation via pulse ox ≤ 85% to 90%.
• Respiratory rate >35 breaths per minute
• Change in patients (Mental status, Accessory muscle use,Onset of diaphoresis)

Rapid Shallow Breathing Index

• RSBI=f (breaths/min)/V+ (liters)
• RSBI >105
• Prognostic of failure
• VE= 5 TO 6 L/min
• VE >10 L/min
• Weaning not likely successful
• Vital Capacity
• 65 to 75 mL/kg IBW
• FVC <20 mL/KG preoperative
• Risk of pulmonary complications
• VC 10 to 15 mL/kg needed for deep breathing and coughing
• Vc >10 to 15 mL/kg for successful weaning and extubation

Integrating Pressure, Flow, and Volume

• Titrating PEEP and tidal volume with P/V
• Static pressure-volume curve
• Super syringe technique
• Time consuming and cumbersome
• Useful in acute lung injury
• Lower inflection point +2 cmH20
• Minimal PEEP
• Upper inflection point
• Overdistention

Dead Space-Tidal Volume Ratio

• VD/VT
• Is a relationship between VD and total VT; the portion of the VT that is "wasted."
• Has two components:
• Anatomic dead space that can be calculated by the equation: 1mL/Ib IBW
• Alveolar dead space are Alveoli that are ventilated but not perfused
• VD/VT= PaC02- PECO2/PaCo2
• Normal is 25% to 40%.

Evaluation of Oxygenation

• Monitoring adequacy of arterial oxygenation
• Oxygen index = Paw × F₁O2 × 100/PaO2
• Ol values less than 5 are considered acceptable
• Values in the 10 to 20 range indicate impaired oxygenation
• Ol above 25 is associated with a severe oxygenation disturbance and poor clinical outcome
• Intrapulmonary shunt
• QS/QT
• Increased in: Atelectasis, PNA, ARDS, Pulmonary edema

Tissue Oxygenation

• Pulse oximetry will reveal low SpO2 with elevated Fi02
• Co-ox useful to determine Ca02
• Oxygen delivery (DO2)
• Is the product of Cardiac Output x CaO2 x 10
• Normal: 550 to 650 mL/mim/m2
• Oxygen Consumption (VO2) follows the Fick principle
• Normal: 100 to 140 ml/min/m2
• Change vol% to mL/L

Blood Oxygenation

• Mixed venous oxygen tension PvO2
• A measure of the partial pressure of oxygen in mixed venous blood
• An indication of oxygen used by the entire body
• Normal: 38 to 42 mm Hg
• Low: inadequate cardiac output, anemia, hypoxia, lactic acidosis
• High: Poor sampling technique, left-to-right shunt, septic shock, increased cardiac output, cyanide poisoning
• Mixed venous oxygen saturation (SvO2)
• Measured from a mixed venous blood sample, Fiberoptic reflectance oximetry

Decreases in Blood Oxygenation

• Suctioning, Shivering, extubation, weaning, PPV
• Arterial-mixed venous oxygen content difference, C(a-v)O2
• reflects the difference in oxygen content between arterial and venous blood
• Normal: 4 to 6 vol%
• Increased: low cardiac output or increasing VO2
• Decreased: septic shock, increased cardiac output, anemia, left shift ODC
• Oxygen extraction ratio [C(a-v)O2/CaO2] expresses the relationship between available oxygen (CaO2) and extracted oxygen
• Normal: 25% to 30%
• Increased: low cardiac output increased VO2 decreased CaO2
• Decreased: high cardiac output or sepsis

Blood Lactate

• Anaerobic metabolism is lactic acid production
• Normal: <1.7 to 2.0 mM/L

• 3.83 mM/L is 67% mortality

• 8 mM/L is 90% mortality

• β-adrenergic stimulator drugs increase lactate levels because of glycolysis
• β-blockers decrease blood lactate levels
• Regional tissue oxygenation is Near infrared spectroscopy
• Assessment is done via a Noninvasive assessment, Normal: >75%
• Decreased likelihood for organ dysfunction
• Sensor placement is important: Determines HbO2 saturation, Matching of O2 delivery + utilization, Vasoconstriction and regional ischemia; Chapter 15: 5, 6, 8, 10, 14-17, 20-40, Box 15.3, Figure 15.9

Introduction and Hemodynamic Waveforms

• Hemodynamic monitoring is important for the assessment and treatment of critically ill patients.
• Used to, Evaluate intravascular fluid volume, Evaluate cardiac function, Evaluate vascular function and Identify sudden changes in the patient's hemodynamic status.
• Invasive monitoring is needed to obtain an accurate evaluation of hemodynamics

Arterial Pressure monitoring and Aterial Pressure Wave Forms

• Indications for arterial catheters, In patients with significant hemodynamic instability, In patients who may need frequent arterial blood gas assessment and Patients receiving medications that affect blood pressure.
• A pressure transducer provides an electrical signal to an amplifier or monitor
• Displays the corresponding pressure waveform
• The arterial pressure wave should have a clear upstroke on the left
• A dicrotic notch on the downstroke on the right and Represents aortic valve closure
• A Disappears in some patients when the systolic pressure drops below 50 or 60 mm Hg
• Increases in heart rate and vascular resistance
• Increase diastolic pressure
• Vasodilation decreases vascular resistance
• A fall in diastolic pressures
• Approximately 70% of coronary artery perfusion occurs during diastole
• Coronary artery perfusion may be compromised if the diastolic pressure falls below 50 mm Hg

Arterial Pressures

• Interpretation of Arterial Pressures
• Pulse pressure
• Difference between systolic and diastolic pressures
• Normal is 30 to 40 mm Hg
• A low pulse pressure is common when stroke volume is low.
• Mean arterial pressure (MAP)
• Normal 70 to 105 mm Hg
• MAP <60 mm Hg compromises the function of vital organs
• Complications of continuous arterial pressure monitoring Ischemia,
• occurs with embolism, thrombus, or arterial spasm.
• Can result in tissue necrosis if not recognized rapidly
• Hemorrhage- occurs if line becomes disconnected
• Infection
• Monitoring CVP
• Indications
• To assess circulating blood volume and filling pressures of the heart
• To assess right ventricular function and patients who have had major surgery or trauma need a CVP catheter
• Can also put medication through CV catheter

CVP Catheter

• Most popular catheter is 7 French with a triple lumen
• One distal port and two ports 3 to 4 cm from the distal end of the catheter
• The triple lumen allows, Infusion of medications, port from which to obtain blood simple
• Common sites for introduction
• subclavian and internal jugular veins

Wave Forms

• Central Venous and Arterial pressure
• Reflects the pressures in the right atrium
• Normal waveforms have three waves
• "a” wave occurs with atrial contraction
• "c,,
• "c" wave occurs with movement of AV valve back toward the atrium during systole
• "v"
• "v" occurs with atrial filling during systole
• Aling transducer has to be level with patient
• Transducer higher, Lower BP
• Transducer Lower, Higher BP

Respiratory Variations

• Spontaneous inspiratory efforts cause CVP to decrease
• Seen on the waveform
• Positive pressure breaths cause the CVP to increase CVP
• monitoring during mechanical ventilation requires brief disconnection of the ventilator
• unless PEEP is being applied

troubleshooting

• The absence of respiratory oscillations on a CVP tracing indicates a measurement error that requires troubleshooting:
• Most likely cause of absent respiratory oscillations
• A Kink or air in the tubing
• A stopcock turned in the wrong direction
• Or a small clot or kink in the catheter
• Rarely, when a hypovolemic patient is breathing spontaneously at small tidal volumes, respiratory oscillations may not be apparent. the typical a, c, and v wave pattern may not be seen

Interpretation and Increased CVP

• Interpretation of CVP
• Causes of increased CVP (Fluid overload, Right/left heart failure, Pulmonary hypertension, Tricuspid valve stenosis, Increased venous return)
• Causes of decreased CVP (Reduced circulating blood volume and spontaneous inspiration)
• Causes of changes in CVP
• Increased pressure (Volume overload or fluids being given more rapidly than the heart can tolerate, increased intrathoracic pressure increases with positive-pressure breath or tension"

PAP and Lung Pressure Changes

• Compression around the heart (Constrictive pericarditis, Cardiac tamponade), Pulmonary hypertension, Right ventricular failure, Left heart failure, Pulmonary embolism, Increased large vessel tone, The body to venoconstriction, Arteriolar vasodilation increasing blood supply to venous system and phlebostatic axis.
• Decreased pressure is vasodilation. Inadequate circulating blood volume caused by (Dehydration, Blood loss, Gastrointestinal loss and Spontaneous inspiration) Placement of transducer above the patient's right atrium phlebostatic axis.

PAP and Lung Function

• PAP monitoring developed to allow better evaluation of left ventricular function.
• Allows assessment of:Left ventricular filling pressure, pulmonary vascular resistance, Arteriovenous oxygen difference and mixed venous oxygen levels.
• Indications, Indications not well defined
• Research shows many complications and may be of limited benefit.

PAP Placements

• Today the PA catheter is placed has these traits: taking into consideration patient's condition and staff qualifications.
• PAP Conditions for using the catheter, severe cardiogenic pulmonary edema, Patients with ARDS, major thoracic surgery and septic or severe cardiogenic shock