multi-organ dysfunction syndrome & pulmonary hypertension

Harvard Medical SchoolBoston Children’s Hospital

Multi-Organ Dysfunction Syndrome & Pulmonary Hypertension

Amy Sanderson, MD

Boston Children’s Hospital


Multi-Organ Dysfunction Syndrome (MODS)


Case example

• 10 year old male with ALL undergoing chemotherapy

• Presented to the ED with febrile neutropenia

• Exam:

– Lethargic and hard to arouse

– Hypotensive and poorly perfused

• Labs:

– Creatinine 2

– AST & ALT 200-300

– INR 1.8

• Fluid resuscitated & pressors initiated

• Intubated


The ICU team documents that he is admitted for septic shock and multi-organ

dysfunction


MODS

• Why do clinicians use the term?

– Easy to explain how sick a patient is

• What’s the problem with the term

– Non-specific

– Can’t code it


What is MODS?

• Clinical syndrome of otherwise unexplained physiologic dysfunction of > 1 organ systems

• It is a continuum of physiologic derangements

– Ranges from mild to irreversible failure

• Induced by a variety of acute insults

– Sepsis, pancreatitis, cardiac arrest, hemorrhagic shock


Pathophysiology

• Unregulated immune response

• Uncontrolled, severe inflammation

• Release of inflammatory mediators/cytokines

• Inadequate perfusion/tissue hypoxia


Respiratory Dysfunction

• Pulmonary vascular endothelial injury

– Disrupted capillary blood flow

– Enhanced microvascular permeability

– Pulmonary edema

• Neutrophil entrapment within the pulmonary microcirculation

– Injury to alveolar capillary membranes

• ALI & ARDS


Respiratory Dysfunction

• Exam: dyspnea, tachypnea, nasal flaring, hypopnea

• Data: O2 sat with hypoxia, blood gas with hypoxia &/or hypercapnia

• Treatment: oxygen, positive pressure

• Documentation: respiratory insufficiency, desats


Respiratory dysfunction

• What should clinicians document?

–Acute (on chronic) respiratory failure

–Acute pulmonary edema

– Pleural effusion

– Pneumothorax


Circulatory Dysfunction

• Vasodilation: inappropriate distribution of blood flow

– More blood flow to periphery

– Ischemia of core organs

– Tachycardia

• Pre-existing heart disease may not be able to tolerate increased metabolic demand


Circulatory Dysfunction• Systolic & diastolic cardiac dysfunction

– Both pre-existing cardiac disease and not

• Mitochondrial dysfunction – end organs cannot extract oxygen sufficiently

• Hypotension

– Endothelial injury: capillary leak/hypovolemia

– Vasodilation: decreased venous return

– Cytokine release: myocardial depression



• Exam: tachycardia, hypotension, delayed or flash capillary refill, cool & mottled skin or flushed skin

• Data: metabolic acidosis, ↑ lactate, ventricular dysfunction

• Treatment: IV fluid boluses, vasoactive infusions

• Documentation: low BP, soft BPs




–Hypotension (at the least!)

–Metabolic acidosis

–Heart failure (with specificity)

– Shock (septic, cardiogenic)


Gastrointestinal Dysfunction

• Overgrowth of bacteria in upper GI tract: aspiration pneumonia

• Alteration of gut mucosal barrier: translocation of bacteria (worsening sepsis)

• Decreased gut motility from sepsis, opioids, paralytics: impaired nutritional intake

• Liver dysfunction: synthetic, transaminitis



• Exam: abdominal distention, RUQ tenderness

• Data: ↑bili, AST & ALT, distended bowel loops on KUB

• Treatment: IV fluid bolus, bowel rest, TPN, methylnaltrexone, laxatives, stool softener

• Documentation: transaminitis, low albumin, weight loss




– Aspiration pneumonia

– Ileus

– Shock liver / ischemic hepatitis

– Malnutrition

– Hypoalbuminemia


Renal Dysfunction

• Decrease in intravascular volume

• Hypotension

• Renal vasoconstriction

• Release of inflammatory mediators/cytokines

• Activation of neutrophils by endotoxins and other peptides


Acute Tubular Necrosis

MedicationsHypovolemia

Low cardiac output states

Systemic vasodilation

DIC

Ischemic

Myoglobin & hemoglobin

Toxic

Crystals

Multiple myeloma


Acute Tubular Necrosis

Initiation

• Hypotension & hypovolemia

• Ischemia

• Injury/death of tubular cells

• Sloughing & cast formation

• Obstruction of tubular lumen

• Cytokines

Maintenance

• Stabilization of GFR at a very low level

• Lasts 1-2 wks

Recovery

• Regeneration of tubular cells

• Sometimes polyuria

• Salt & H2O loss


Renal Dysfunction

• Exam: delayed capillary refill, cool & mottled extremities, thready pulses, AMS, oozing

• Data: ↑ BUN & Cr, ↑K & Phos, ↑/↓ Na, ↓HCO3

• Treatment: IV fluid bolus

• Documentation: renal insufficiency, azotemia, requiring IHD or CVVHD, diuretics


Renal Dysfunction


– Acute kidney injury/failure

• With ATN, if present

– Underlying CKD (with stage)


Coagulation Defects

• Ranges from mild coagulopathy to DIC

• Exam: bleeding, bruising, purpura fulminans

• Data: ↑INR, PT & PTT, ↓ fibrinogen, ↑D-dimer, ↓ PLT

• Treatment: PLTs, FFP, cryoprecipitate

• Documentation: abnormal coags, prolonged INR


Coagulation Defects


– Coagulopathy

– DIC

– Thrombocytopenia

– Anemia (acute blood loss)


MODS

• Clinical syndrome of otherwise unexplained physiologic dysfunction of > 1 organ systems

• It is a continuum of physiologic derangements

– Ranges from mild to irreversible failure

• Induced by acute insults

• Goal is to treat dysfunction of individual organ systems as well as the underlying cause


Pulmonary Hypertension


Case example

• Newborn female with a pre-natal diagnosis of left CDH

• Intubated at birth

• ABG with a significant respiratory and metabolic acidosis.

• Echocardiogram:

– Moderate RV systolic dysfunction

– Moderate PDA with flow going across the PDA to the aorta

– Supra-systemic PA pressures


The ICU team documents that the patient is started on inhaled nitric oxide due to

elevated PA pressures


What is pulmonary hypertension?

• Complex, progressive disease affecting both children and adults

– Leads to significant morbidity and mortality

• Mean pulmonary artery pressure ≥ 25mmHg when the patient is at rest

Hansmann G. J Am Coll Cardiol. 2017 May 23; 69(20): 2551-2569

Oishi P, Fineman JR. Pediatr Crit Care Med. 2016 Aug; 17(8 Suppl 1): S140-5


WHO classification

• Group 1 - PAH

• Group 2 - PH due to left-sided heart disease

• Group 3 – PH due to lung diseases and/or hypoxia

• Group 4 - Chronic thromboembolic PH

• Group 5 – PH with unclear or multifactorial etiologies

Simonneau G, et al. J Am Coll Cardiol. 2009 Jun 30. 54(1 Suppl):S43-54


Causes of pulmonary hypertensionCongenital heart disease

Lung disease/chronic hypoxia (BPD, COPD, OSA, interstitial lung disease)

Idiopathic

Heritable

Persistent PH of the newborn

Congenital diaphragmatic hernia

Glycogen storage disease

Connective tissue disease

Chronic pulmonary embolism

Ischemic left heart disease

Cardiomyopathy

Myocarditis

Drug-induced (chemotherapy, cocaine)

Hematologic disorders (chronic hemolytic anemia, myeloproliferative disorders, splenectomy)

Chronic renal failure

Portal hypertensionSimonneau G, et al. J Am Coll Cardiol. 2009 Jun 30. 54(1 Suppl):S43-54


Pathophysiology

Vasoconstriction

ThrombosisRemodeling


Pathophysiology

High resistance in the pulmonary vascular bed

Blood flow obstructed from the RV to the lungs

Increased blood volume & pressure in RV (↑work!)

Over time, the RV dilates and thickens

RV dysfunction & failure


PH crisis

↑↑ RV pressure and volume

Interventricular septum shifts to the left

LV’s ability to fill is impeded

↓ cardiac output & systemic oxygen delivery

Hypoxia, metabolic acidosis & possibly death


Signs & symptoms

• Dyspnea with exertion

• Fatigue

• Lethargy

• Syncope

• Cyanosis

• Anorexia & weight loss

• Cough

• Chest pain

• RUQ pain


Exam

• Systolic ejection murmur over L sternal border

– May be louder during inspiration

• 4th heart sound (S4): “Tennessee”

• RV failure

– Hepatomegaly

– Ascites

– Peripheral edema

– 3rd heart sound (S3): “Kentucky”


Diagnostic studies

• PA catheter readings

• Echocardiogram

• Chest CT

• Cardiac MRI

• Cardiac catheterization


Therapies

• Oxygen

• Pulmonary vasodilators

• Inotropic/vasoactive agents

• Diuretics

• Calcium channel & beta blockers

• Anticoagulation

• Bicarbonate

• Sedation & paralysis

• Surgical therapies


Documentation

• Elevated PA or wedge pressure

• RV strain

• RV hypertrophy

• RV dysfunction

• Pulmonary vasoreactivity

• Nitric oxide responder


Pulmonary Hypertension

• Complex, progressive disease affecting both children & adults, leading to significant morbidity and mortality

• There are many causes of PH

• There may be many clues in the medical record, including history, exam, diagnostics, therapies & documentation that may point to the diagnosis of PH

multi-organ dysfunction syndrome & pulmonary hypertension

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