CLINICAL AND PHYSIOLOGICAL BACKGROUND FOR THE ICU DATA SET

This document is intended to help researchers with non-medical 
backgrounds to understand the problem domain and interpret the data 
covered in the ICU data set.  The medical information presented here is 
not complete and may not represent all pertinent points of view.  We 
aimed for simplicity and tried to avoid unnecessary detail; interested 
researchers can solicit our help or consult fellow clinicians for further 
references when necessary.

Serdar Uckun, AIM-94 Co-Chair
8/27/1993
aim-94@camis.stanford.edu

1. PROBLEM DOMAIN

Adult respiratory distress syndrome (ARDS) is a pathophysiological 
entity or complex which is characterized by acute and diffuse lung injury.  
The lung injury presents with several typical findings which make up a 
clinical syndrome.  The clinical definition includes respiratory distress, 
tachypnea (increased respiratory rate), severe hypoxemia (low oxygen 
partial pressures in arterial blood due to improper oxygenation of blood 
in the lungs), decreased pulmonary compliance, and specific X-ray 
findings.  The major mechanism behind these symptoms is increased 
permeability of lung capillary blood vessels, resulting in the collection of 
protein-rich fluids in alveolar spaces (the gas exchange compartments of 
the lung), thus limiting the surface area for gas exchange and stiffening 
the lungs in general.  The syndrome may be triggered by a variety of 
causes such as trauma, sepsis, aspiration, fractures, burns, certain drug 
overdoses, smoke inhalation, etc.  Although the definition of the 
syndrome varies from site to site, all definitions refer to a group of 
patients requiring mechanical ventilation with high fractions of inspired 
oxygen.  An estimated 150,000 cases occur each year in the U.S. alone 
and the mortality, despite significant advances, is over 50%.  As a final 
note, ARDS is a misnomer since it occurs in all age groups (the case 
presented here is 8.5 months old).  

2. TREATMENT

The treatment of ARDS includes assisted ventilation, cardiovascular 
support, and treatment of the underlying cause which triggered ARDS.  

2.1. Assisted Ventilation

The increased compliance of lungs  and decreased surface area for gas 
exchange affects two major functions of the respiratory system: 1) 
oxygenation (uptake of oxygen from the air) and 2) ventilation (removal 
of carbon dioxide from blood).  Hence, the principal findings include low 
arterial O2 partial pressure (PaO2), high arterial CO2 partial pressure 
(PaCO2), and low blood pH.  The last problem, referred to as acidosis 
(and, in this case, as "respiratory acidosis"), is caused by the excess CO2 
in the blood which maintains an equilibrium with carbonic acid.  

Mechanical ventilation aims to correct all three problems.  A mechanical 
ventilator is a device which partially or completely takes over the duty 
of ventilating a patient's lungs.  There are several methods by which this 
may be achieved; we will focus on the method used on the patient 
discussed in this data set.  In this case, a mode called "continuous 
mandatory ventilation" (or controlled mechanical ventilation) is used 
(CMV).  The mechanical ventilator used here is pressure-limited and 
time-cycled.  During the inspiratory phase of a breathing cycle, the 
ventilator delivers a constant flow of gas until a preset pressure limit is 
reached.  This limit is referred to as peak inspiratory pressure (PIP).  
From there on, the ventilator maintains that pressure in the airways until 
the end of the inspiration phase.  Expiration is passive; the recoil 
tendency of the lungs helps expel the gas out.  However, the ventilator 
maintains a preset positive pressure during expiration in order to 
prevent the alveolar spaces from collapsing.  This preset limit is referred 
to as positive end-expiratory pressure (PEEP).  The respiratory rate 
(breaths per minute) and the inspiratory time (or the 
inspiratory/expiratory time ratio (I:E)) are set on the ventilator.  A final 
setting on the ventilator is the volume fraction of inspired oxygen (FiO2), 
which is almost always maintained at levels above the atmospheric O2 
fraction of 21%.  In this mode, tidal volume (TV -- the volume of gas 
circulated with each breath) is a dependent parameter; it depends on the 
pressure differential and the compliance of the lungs.

2.1.1. Oxygenation

The uptake of O2 from the inspired gas into blood is influenced by 
several aspects of assisted ventilation:

* An increase in FiO2 almost invariably increases oxygenation (however, 
high FiO2s are associated with toxic effects and thus the extended use of 
high FiO2s is not always desirable).

* An increase in mean airway pressure increases oxygenation.  Mean 
airway pressure is the average pressure exerted in the airways during the 
complete inspiration/expiration cycle.  Mean airway pressure is 
positively correlated with the pressure differential (PIP - PEEP), the 
baseline pressure (PEEP), and with the I:E ratio.  A mathematical 
representation is:

	MAP = K * (PIP - PEEP) * (IT/(IT + ET)) - PEEP   

where K is a constant, IT and ET are inspiratory and expiratory times, 
respectively.

Although higher pressures seem desirable, there are adverse effects 
associated with the use of high pressures such as trauma to the lungs 
and interference with cardiovascular function (increased pressure in the 
chest cavity --> pressure on vessels returning blood to the heart).

Another parameter, arterial O2 Saturation (measured as a percentage), 
correlates positively with PaO2.  O2 SAT is clinically important because 
it is easier to measure than PaO2 (which typically requires arterial blood 
gas measurements, a costly and risky procedure).  Treatment often aims 
to keep O2 SATs around 93-95% whereas the normal value for a healthy 
person is close to 100%.  Normal PaO2 in a healthy person is around 
100 mmHg; adequate oxygenation support targets PaO2 values around 
70-80 mmHg.

2.1.2. Ventilation

Rate of removal of CO2 from the blood positively correlates with minute 
ventilation, which is calculated as tidal volume * respiratory rate (RR).  
Tidal volume is positively influenced by the pressure differential (PIP - 
PEEP) and lung compliance.  Normal PaCO2 values are between 35-45 
mmHg; patients can typically tolerate mild hypercapnia (slightly higher 
values) if high peak pressures or respiratory rates are not desirable.

2.1.3. Acid-Base Balance

In many cases, correction of the ventilation problem (removal of excess 
CO2) also corrects the respiratory acidosis problem.  Normal arterial 
blood pH is around 7.38 to 7.42; lower values constitute the acidosis 
range.

2.2. Cardiovascular Support

Correction of oxygenation only solves half of the problem of oxygen 
delivery.  Another equally important aspect of oxygen delivery to tissues 
is the pumping ability of the heart (O2 delivery is the product of arterial 
blood O2 content and cardiac output).  The level of cardiovascular 
support depends on preexisting and underlying conditions.  In general, 
four classes of measures may be useful:

1. Increase the O2-carrying capacity of blood (increase hemoglobin 
concentration by means of transfusions).
2. Increase preload (i.e., venous return to the heart) by means of fluid 
support.
3. Increase the pumping ability of the heart (use of inotropic agents such 
as dopamine).
4. Decrease afterload (i.e., the resistance against which the heart has to 
pump) either by using vasodilators (drugs that relax smooth muscles in 
blood vessel walls) or as a side effect of improved O2 delivery to tissues 
(increased O2 utilization --> increased local blood circulation  --> 
vasodilation).

2.3 Other Treatments

Other treatments typically include corrective measures for the triggering 
cause and other coexisting problems such as infections and other organ 
failures.  Mechanically ventilated patients are often sedated and muscle-
relaxed in order to reduce their own respiratory efforts.  This helps 
further minimize their oxygen demands and reduce the pressure support 
required to ventilate the patient against the resistance of their own 
respiratory muscles.  Finally, treatment often includes the use of 
bronchodilating agents (drugs which relax airways).


3. SPECIFICS ABOUT THE PRESENTED CASE

3.1. Patient Description

The patient presents as a typical ARDS case which follows a congenital 
bile duct anomaly, high-risk corrective surgical procedure, infection of the 
biliary tract and the liver, and sepsis (spread of the infection into the 
bloodstream).  The problem is complicated with  coagulation defects, 
most probably induced by the liver insufficiency.  The treatment listed in 
the patient description includes nystatin (an anti-fungal agent to prevent 
opportunistic fungal infections), ativan (a tranquilizer), bladder 
irrigation to prevent infections, nebulized ventolin (a bronchodilator), 
and maalox (an antacid).

3.2. Monitor Data

This large set of data covers a period of approx. 12 hours during the ICU 
treatment of this patient under mechanical ventilation.  Time-stamped 
data points represent various monitored parameters and ventilator 
settings.  The data codes are included in a separate file (Monitor-Data-
Codes).  Blood pressures, O2 SATs, and heart rate are monitored 
continuously (approx. once every fifteen seconds).  The data presented 
in the Monitor-Data file is compressed; values for continuously 
monitored parameters remain steady between consecutive recorded 
measurements and thus the lack of recorded measurements should not be 
interpreted as lack of data.  The ventilator settings (FiO2, RR, PIP, and 
PEEP) are only recorded in case of a setting change.  Other dependent 
parameters (mean airway pressure and tidal volume) are recorded 
occasionally.

There are two sources for heart rate in the data file: ECG and the blood 
pressure monitor.  In case of conflicts, the heart rate reading coming from 
the ECG monitor is more reliable.

Two modes of ventilation are used on this patient.  In addition to CMV, 
the patient is disconnected from the ventilator approximately once every 
two hours and ventilated using a hand bag for approx. 10 to 15 minutes 
per session.  During these sessions, the FiO2 is increased from 50% to 
100% (which results in temporary increases in O2 saturation).  The 
purpose of these sessions is to deliver a bronchodilator in aerosol form 
(ventolin) directly to the airways.  This drug dilates the airways and 
thus reduces the resistance to gas flow, which may result in an increase 
in mean airway pressures.  In addition, this process helps "recruit" some 
previously-occluded alveolar spaces and thus improve ventilation. The 
effects of ventolin start appearing after 5 minutes and typically last 1.5-
2 hours.

3.3. Flowsheet Data

The flowsheet data include the treatment records obtained from patient 
flowsheets during the same period of time.  All mentioned drugs are 
administered via drip infusion; administration and doses should be 
interpreted to persist throughout the record unless a new order is 
indicated.  The fluid balance (important for preload considerations) may 
be calculated by integrating the fluid input and output rates over this 
period.  The drugs infused during this period are:

* terbutaline: a bronchodilator
* pavulon: a neuromuscular blocking agent which is used to paralyze the 
patient to aid mechanical ventilation 
* versed: a short-acting sedative from the benzodiazepine family
* fentanyl: a potent narcotic analgesic used for sedation and analgesia 
* dopamine: a positive inotropic agent (i.e., used to increase cardiac 
contractility).  Note that dopamine is used over a wide range of doses 
over this time period.  In general, at doses below 2 mcg/kg/min, it is 
used to increase blood flow to kidneys, thus increasing renal blood flow 
and urine output.  At moderate levels (2-5 mcg/kg/min), it increases 
cardiac output, stroke volume, and heart rate with no effect on systemic 
vascular resistance or blood pressure.  At levels in excess of 5-10 
mcg/kg/min, it increases systemic arterial pressure in addition to its 
inotropic effects.

3.4. Lab Data

The following list presents the lab codes and the normal ranges for each 
parameter.  Note that "normal" values vary from one laboratory to 
another and thus should not be interpreted as absolute truth.  Where 
available, listed normal values are for 1/2 to 1 year old females.

3.4.1. Coagulation Tests

FIB			Plasma fibrinogen (normal: 170-340 mg/dl) A 
			protein required for coagulation.

PLT			Platelet count (normal: > 150,000/mm3). Low 
			values indicate a coagulation defect or excessive 
			loss of platelets (continued bleeding, etc.).

PT, PT1, PT2		Prothrombin time (normal control values are 
			indicated by PT; patient's values are listed as 
			PT1 or PT2; in seconds).  Elevated values indicate 
			coagulation defects.

PTT, PTT1, PTT2		Partial thromboplastin time (same nomenclature as 
			PT).  Elevated values indicate coagulation defects.


3.4.2. Blood Chemistry

ALB			Serum albumin (normal: 3.5-5.5 g/dl)

ALT			Alanine aminotransferase (SGPT) (normal: 10-40 U/L)  
			High levels have a similar significance as for AST.

AST			Aspartate aminotransferase (SGOT) (normal: 10-40 U/L) 
			High levels of this enzyme indicate liver cell damage.

BILITOTAL		Total bilirubin (normal: 0.3-1.0 mg/dl)

BUN			Blood urea nitrogen.  A measurement of kidney 
			function (normal: 6-26 mg/dl).  Increased levels 
			indicate renal insufficiency.

CL			Serum chloride (normal: 98-106 mEq/L)

CR			Serum creatinine (normal:0.5-1.5 mg/dl) another 
			indicator of renal function; high levels indicate 
			renal insufficiency.

GLU			Blood glucose (normal (fasting): 70-110 mg/dl)

IONCA			Serum ionized calcium (normal: 2.3-2.8 mEq/L)

K			Serum potassium (normal: 3.5-5 mEq/L)

MG			Serum magnesium (normal: 1.5-2.5 mEq/L)

NA			Serum sodium (normal: 136-145 mEq/L)

NH3			Whole blood ammonia (normal: 80-110 mcg/dl) 
			Elevated in patients with liver disease.

PHOS			Serum inorganic phosphate (normal: 3-4.5 mg/dl)

TP			Serum total protein (normal: 5.5 - 8 g/dl)

TRIG			Serum triglycerides (normal: 40-130 mg/dl)

3.4.3. Hematologic Tests

HCT			Hematocrit (normal: 35-45%) Indicates the 
			concentration of red cells in blood.

HGB			Hemoglobin concentration (normal: 10-14.5 g/dl) 
			An indicator of the oxygen-carrying capacity of 
			blood.

MCH			Mean corpuscular hemoglobin (normal: 27 pg.)

MCHC			Mean corpuscular hemoglobin concentration 
			(normal:34 g/dl )

MCV			Mean corpuscular (i.e., red blood cell) volume 
			(normal: 80 fl.)

RBC			Red blood cell count (normal: 3.8-5.0 million/mm3)

WBC			White blood cell count (normal: 4,500-10,000/mm3)

3.4.4. Blood Gas Measurements

BICARBART		Arterial sodium bicarbonate concentration (normal: 
			21-27 mEq/L)

CO2 			Plasma CO2 content (normal: 21-30 mEq/L)  

O2SATART		Arterial O2 saturation as measured via blood gas 
			(normal: 95-99%)

PCO2ART			PaCO2 measured via arterial blood gas analysis 
			(normal: 35-45 mmHg)

PHART			Arterial pH (normal: 7.38-7.42)

PO2ART			PaO2 measured via arterial blood gas analysis 
			(normal: 95-105 mmHg)


